PMID- 19573616
TI  - Phenotypic analysis of genes whose mRNA accumulation is dependent on calcineurin
      in Aspergillus fumigatus.
AB  - Calcineurin plays an important role in the control of cell morphology and
      virulence in fungi. Calcineurin is a serine/threonine-specific protein
      phosphatase heterodimer consisting of a catalytic subunit A and a regulatory
      subunit B. A mutant of Aspergillus fumigatus lacking the calcineurin A (calA)
      catalytic subunit exhibited defective hyphal morphology related to apical
      extension and branching growth, which resulted in drastically decreased
      filamentation. Here, we investigated which pathways are influenced by A.
      fumigatus calcineurin during proliferation by comparatively determining the
      transcriptional profile of A. fumigatus wild type and DeltacalA mutant strains.
      Our results showed that the mitochondrial copy number is reduced in the DeltacalA
      mutant strain, and the mutant has increased alternative oxidase (aoxA) mRNA
      accumulation and activity. Furthermore, we identified four genes that encode
      transcription factors that have increased mRNA expression in the DeltacalA
      mutant. Deletion mutants for these transcription factors had reduced
      susceptibility to itraconazole, caspofungin, and sodium dodecyl sulfate (SDS).

PMID- 19573617
TI  - Role of Nod2 in the development of Crohn's disease.
AB  - Crohn's Disease (CD) is caused by a loss of the regulatory capacity of the immune
      apparatus. Nod2 is an intracellular bacterial sensor and its mutations are
      associated with the development of CD. Here we summarize recent and controversial
      findings about the role of the Nod2 mutants in the disease process.

PMID- 19573618
TI  - Innate immune responses to Encephalitozoon species infections.
AB  - Microsporidia are obligate intracellular, eukaryotic fungi, which have gained
      recognition as opportunistic parasites in immunocompromised patients. Resistance
      to lethal microsporidia infections requires a Th1 immune response; how this
      protection is initiated against Encephalitozoon species is the focus of this
      review article.

PMID- 19573619
TI  - High susceptibility to respiratory Acinetobacter baumannii infection in A/J mice
      is associated with a delay in early pulmonary recruitment of neutrophils.
AB  - Acinetobacter baumannii is an important cause of both community-associated and
      nosocomial pneumonia, which have become increasingly difficult to treat because
      of the rapid development of resistance to multiple antibiotics. Despite its
      clinical importance, the pathogenesis of and host defense against respiratory A.
      baumannii infection remains largely unknown. To examine host factors that could
      contribute to the defense, we compared the susceptibilities of A/J and C57BL/6
      mice to intranasal (i.n.) inoculation with A. baumannii. We found that A/J mice
      were significantly more susceptible to infection with higher mortality (P<0.05)
      and tissue bacterial burdens (P<0.01) as well as greater histopathology in the
      lung and spleen than C57BL/6 mice. More importantly, the high susceptibility of
      A/J mice was associated with a reduced local proinflammatory cytokine/chemokine
      (particularly IL-1beta, MIP-2 and TNF-alpha) responses and a significant delay
      and reduction in the early influx of neutrophils in the lung (P<0.05). Intranasal
      administration of neutrophil-inducing chemokine MIP-2 to A/J mice enhanced
      pulmonary neutrophil influx and partially restored host resistance to A.
      baumannii to a level comparable to the more resistant C57BL/6 mice. Our results
      imply that the early recruitment of neutrophils into the lung is critical for
      initiating an efficient host defense against respiratory A. baumannii infection.

PMID- 19573620
TI  - The critical role of the conjunctiva in glaucoma filtration surgery.
AB  - This review considers the critical role of the conjunctiva in determining the
      success or failure of glaucoma filtration surgery. Glaucoma filtration surgery
      can be defined as an attempt to lower intraocular pressure (IOP) by the surgical
      formation of an artificial drainage pathway from the anterior chamber to the
      subconjunctival space. Many types of glaucoma filtration surgery have been
      developed since the first attempts almost 180 years ago. The wide range of new
      techniques and devices currently under investigation is testament to the
      limitations of current techniques and the need for improved therapeutic outcomes.
      Whilst great attention has been paid to surgical techniques and devices to create
      the drainage pathway, relatively little attention has been given to address the
      question of why drainage from such artificial pathways is often problematic. This
      is in contrast to normal drainage pathways which last a lifetime. Furthermore,
      the consequences of potential changes in aqueous humour properties induced by
      glaucoma filtration surgery have not been sufficiently addressed. The mechanisms
      by which aqueous fluid is drained from the subconjunctival space after filtration
      surgery have also received relatively little attention. We propose that factors
      such as the degree of tissue damage during surgery, the surrounding tissue
      reaction to any surgical implant, and the degree of disruption of normal aqueous
      properties, are all factors which influence the successful formation of long term
      drainage channels from the conjunctiva, and that these channels are the key to
      successful filtration surgery. In recent years it has been suggested that the
      rate of fluid drainage from the subconjunctival space is actually the determining
      factor in the resultant IOP reduction. Improved knowledge of aqueous humour
      induced changes in such drainage pathways has the potential to significantly
      improve the surgical management of glaucoma. We describe for the first time a
      novel type of drainage surgery which attempts to minimise surgical trauma to the
      overlying conjunctiva. The rationale is that a healthy conjunctiva allows
      drainage channels to form and less opportunity for inflammation and scar tissue
      formation which are a frequent cause of failure in glaucoma filtration surgery.
      Successful drainage over extended periods of time has been demonstrated in monkey
      and rabbit eyes. Long lasting drainage pathways were clearly associated with the
      presence of lymphatic drainage pathways. A new philosophy in glaucoma drainage
      surgery is proposed in which minimisation of surgical trauma to the conjunctiva
      and the encouragement of the development of conjunctival drainage pathways,
      particularly lymphatic pathways, are central pillars to a successful outcome in
      glaucoma filtration surgery.

PMID- 19573622
TI  - Cleavage and gastrulation of the dendrobranchiate shrimp Penaeus monodon
      (Crustacea, Malacostraca, Decapoda).
AB  - The cleavage pattern of the black tiger shrimp Penaeus monodon was analyzed from
      the first division until gastrulation. Observations were based on microscopy
      combined with the use of fluorescent dyes, histological techniques, and computer
      based three-dimensional reconstructions. Early cleavage is holoblastic and
      follows a stereotypic pattern, which largely corresponds to what is known from
      other dendrobranchiate decapods. However, for the first time in this group, we
      report the presence of an intracellular structure throughout early development.
      This intracellular body (icb) marks the lineage of one of the two enlarged and
      division-delayed mesendoderm cells that initiate gastrulation. The identity of
      the icb as a natural marker and putative determinant of the germ line and its
      implications on the establishment of the body axes are discussed. The icb as a
      landmark reveals that the same stereotypic cell division pattern can lead to
      different fates of individual cells. Hence, the results of this study permit an
      additional approach to study the relation between cell lineage pattern and the
      identity of cell lineages.

PMID- 19573621
TI  - Lipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing
      organelles: a MCP-1/CCL2 regulated phenomenon.
AB  - Lipid-laden foam macrophages are emerging as key players in early atherogenesis.
      Even though cytoplasmic lipid bodies (lipid droplets) are now recognized as
      organelles with cell functions beyond lipid storage, the mechanisms controlling
      lipid body biogenesis within macrophages and their additional functions in
      atherosclerosis are not completely elucidated. Here we studied oxLDL-elicited
      macrophage machinery involved in lipid body biogenesis as well as lipid body
      roles in leukotriene (LT) synthesis. Both in vivo and in vitro, oxLDL (but not
      native LDL) induced rapid assembly of cytoplasmic lipid bodies-bearing ADRP
      within mice macrophages. Such oxLDL-elicited foamy-like phenotype was a pertussis
      toxin-sensitive process that depended on a paracrine activity of endogenous MCP
      1/CCL2 and activation of ERK. Pretreatment with neutralizing anti-MCP-1/CCL2
      inhibited macrophage ADRP protein expression induced by oxLDL. By directly immuno
      localizing leukotrienes at their sites of synthesis, we showed that oxLDL-induced
      newly formed lipid bodies function as active sites of LTB(4) and LTC(4)
      synthesis, since oxLDL-induced lipid bodies within foam macrophages
      compartmentalized the enzyme 5-lipoxygenase and five lipoxygenase-activating
      protein (FLAP) as well as newly formed LTB(4) and LTC(4). Consistent with MCP
      1/CCL-2 role in ox-LDL-induced lipid body biogenesis, in CCR2 deficient mice both
      ox-LDL-induced lipid body assembly and LT release were reduced as compared to
      wild type mice. In conclusion, oxLDL-driven foam cells are enriched with
      leukotriene-synthesizing lipid bodies--specialized organelles whose biogenic
      process is mediated by MCP-1/CCL2-triggered CCR2 activation and ERK-dependent
      downstream signaling--that may amplify inflammatory mediator production in
      atherosclerosis.

PMID- 19573623
TI  - Functional anatomy of vagina muscles in the blood-feeding insect, Rhodnius
      prolixus.
AB  - The physiology of the muscles associated with the vagina in the blood-feeding
      insect, Rhodnius prolixus Stal, was investigated with the use of Methylene Blue
      staining to visualize the anatomy, and a micro force transducer to record
      spontaneous and neurally-evoked contractions. The vagina is associated with a
      dorsal muscle and a set of paired lateral muscles. The dorsal muscle extends from
      the base of the common oviduct to apodemes located laterally on sternite VIII,
      the first genital segment. The lateral muscles extend from a medially-located
      apodeme on the posterior edge of sternite VI around each side of the common
      oviduct to travel posteriorly along the side of the vagina before inserting
      laterally on apodemes on sternite VIII. The vagina muscles display spontaneous
      and neurally-evoked contractions that are prolonged but transient. The response
      to evoked contractions shows that the muscles are innervated by both excitatory
      and inhibitory motor axons. The degree of tension generated by evoked
      contractions is dependent on the frequency of stimulation with maximal tension
      being generated at 20-30Hz. This tension, which often exceeds 400mg, is transient
      and returns to a baseline within 1 to 2min during continuous stimulation. These
      results, which are the first to describe this chamber in this well-studied
      insect, are discussed with respect to the act of egg laying.

PMID- 19573624
TI  - Oxidative stress, DNA damage and antioxidant enzyme gene expression in the
      Pacific white shrimp, Litopenaeus vannamei when exposed to acute pH stress.
AB  - The ROS production, the percentage of dead and damaged haemocytes, the DNA Olive
      Tail Moment (OTM) value and the gene expression of manganese superoxide dismutase
      (MnSOD), catalase (CAT), glutathione peroxidase (GPx) and thioredoxin (TRx), were
      studied in the Pacific white shrimp, Litopenaeus vannamei, when exposed to acute
      pH stress. The increased ROS production in haemocytes and the increased OTM value
      in both the haemocytes and the hepatopancreas cells suggest that oxidative damage
      occurred in shrimp exposed to pH 5.6 and pH 9.3, with apoptosis, mainly being
      associated with excess Ca(2+)influx and changes in cell viability. Acid and
      alkaline pH-induced DNA damage was time dependent in the haemocytes and the
      hepatopancreas cells. The concentration of intracellular free calcium [Ca(2+)]
      (i) after different pH treatments increased significantly over time, reaching its
      highest concentration after 12 h, but decreasing gradually to normal levels after
      24 h. The [Ca(2+)] (i) content in shrimp cells when exposed to pH 9.3 and pH 5.6
      for 12 h had increased by 58%-81%, compared with exposure to pH 7.4 (control). In
      addition, the gene expression of cMnSOD, CAT, GPx and TRx in the hepatopancreas
      of L. vannamei was induced by acid and alkaline pH stress, although there were
      differences in the expression response with respect to the duration of induction
      and the different pH treatments (acid or alkaline). Our results show that acidic
      or alkaline-induced oxidative stress may cause DNA damage, and cooperatively
      activate expression of CAT, GPx and TRx mRNA. Calcium ions appear to be important
      in mediating shrimp responses to pH stress.

PMID- 19573625
TI  - Attrition and retention in clinical trials by ethnic origin.
AB  - CONTEXT: Common perceptions exist within the medical community that retention of
      Hispanics in clinical trials is difficult, albeit little data is available to
      support this conviction. METHODS: A total of 541 randomly selected charts from
      closed clinical trials between 2000 and 2006 were reviewed. Records were from
      participating institutions in Texas Medical Center, Houston, and targeted
      diseases of high prevalence, specifically, breast cancer, prostate cancer, and
      chronic obstructive pulmonary disease (COPD)/asthma. FINDINGS: Overall, 259
      participants (48%) completed the trial they were enrolled in (44% whites, 69%
      Hispanics, 51% blacks; p<.05). Within pediatric trials, whom all were pulmonary
      patients, retention rates were higher among Hispanics than whites (adjusted odds
      ratio [OR]=7.49, 95% confidence interval [CI]=1.15-58.03, p=.04). Among adults,
      patient's ethnicity was unrelated to study completion. All associations were
      adjusted for possible confounders. Reasons for not completing a trial varied by
      ethnicity: "patient withdrawing consent" was more common among whites (51.4%)
      than Hispanics (21.7%) or blacks (26.2%) (p<.05). Hispanics were more inclined to
      be withdrawn from the trial by the investigator (43.5%) than were whites (24%,
      p=.04), mostly due to non-compliance with the study protocol. CONCLUSIONS:
      Hispanic parents of children with COPD may be more likely to complete a trial
      than parents of non-Hispanic whites. Among adults, Hispanics had similar
      completion rates as compared to whites. Culturally sensitive, multi-factorial
      approaches maybe imperative to increasing patient engagement in clinical trials.

PMID- 19573626
TI  - Maitake beta-glucan enhances granulopoiesis and mobilization of granulocytes by
      increasing G-CSF production and modulating CXCR4/SDF-1 expression.
AB  - Previous studies have presented that Maitake beta-glucan (MD-Fraction) extracted
      from the fruit body of Grifola frondosa has an anti-tumor effect by activating
      the immune system. Recently, the stimulating effects of beta-glucans on
      hematopoiesis were identified as new characteristics of polysaccharides, possibly
      helping to relieve the immunosuppression which results from chemotherapies. We
      demonstrated that the production of granulocyte colony-stimulating factor (G-CSF)
      was significantly enhanced by MD-Fraction (8mg/kg, i.p.) in granulocytopenic
      model induced in mice using cyclophosphamide (200mg/kg, i.p.). In addition, MD
      Fraction induced a biphasic increase in the number of granulocytes in the spleen.
      The mechanism for the increase in granulocytes on the early phase on day 1 might
      involve the increased mRNA expression of macrophage inflammatory protein-2 (MIP
      2), in the splenic cells, thereby recruiting granulocytes into the spleen.
      Interestingly, a decline of myeloid progenitors in the bone marrow and an
      increase in granulocytes in the peripheral blood were observed on day 5,
      suggesting a mobilization of granulocytes and their progenitors from the bone
      marrow to the peripheral blood. We confirmed that a possible mechanism in which
      MD-Fraction promoted the mobilization of granulocytes and their progenitors from
      the bone marrow is down-regulating the expression of the chemokine receptor,
      CXCR4, and its ligand, stromal cell-derived factor 1 (SDF-1) in the bone marrow
      microenvironment. These results reveal a novel function of Maitake beta-glucan
      that enhances the granulopoiesis and mobilization of granulocytes and their
      progenitors by stimulating G-CSF production. This finding presents opportunities
      to develop new therapeutic strategies against the immunosuppression caused by
      chemotherapies in cancer patients.

PMID- 19573627
TI  - Does the use of recombinant AAV5 in pulmonary gene therapy lead to lung damage?
AB  - This study investigated whether repeated administration of recombinant adeno
      associated virus type 5 (rAAV5) to the airways induces inflammatory processes in
      the lungs of BALB/c-mice, with mechanical and histologic changes. Saline was
      instilled intratracheally in the control group, and rAAV5-green fluorescence
      protein (GFP) (4x10(11)particles) in the virus group (VR). These groups were
      subdivided into four subgroups: one dose analyzed 3 weeks later (VR1d3w) and two
      doses analyzed 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after the second dose.
      Lung morphometry, mechanical parameters, airway responsiveness, rAAV5-GFP
      transduction and the expression of inflammatory cytokines were investigated. No
      significant differences in lung mechanics, airway responsiveness, and morphometry
      were observed. Re-administration of rAAV5 vector resulted in a decrease in GFP
      mRNA expression in the VR2d3w group. There was no evidence of inflammatory
      response or apoptosis in any group. rAAV5 did not induce an inflammatory process,
      mechanical or morphometric changes in the lungs. AAV5 may be an appropriate
      vector for lung gene therapy.

PMID- 19573628
TI  - Foreword: Respiratory rhythmogenesis.
AB  - This special issue of Respiratory Physiology & Neurobiology summarizes the
      current standing of research concerned with synaptic mechanisms, membrane
      properties, plasticity, pre- and postnatal development and evolutionary origin of
      neurones involved in respiratory rhythm generation and central chemosensitivity.
      Moreover, a variety of articles link pathophysiological alterations of synaptic
      function in rhythmogenesis and chemosensitivity with breathing disorders in
      neurodevelopmental diseases.

PMID- 19573629
TI  - Asymptomatic occult cysto-biliary communication without bile into cavity of the
      liver hydatid cyst: a pitfall in conservative surgery.
AB  - BACKGROUND: An occult cysto-biliary communication in liver hydatid disease is
      still a major problem in surgical practice. Radiologic and intraoperative
      findings may not be helpful to detect cysto-biliary communications in some
      asymptomatic patients with liver hydatid disease. Biliary leakage is a troubling
      complication that arises after conservative surgery in patients who have occult
      "insidious" cysto-biliary communications. We aimed to identify the factors which
      are associated with the risk of occult insidious cysto-biliary communications in
      patients preoperatively who developed biliary leakage after surgery. PATIENTS AND
      METHODS: We investigated the records of 183 asymptomatic patients treated for
      liver hydatid cyst and analyzed potential predictors of occult insidious cysto
      biliary communication, retrospectively. RESULTS: There were 115 female and 68
      male patients; the mean age was 42.3 years. Occult insidious cysto-biliary
      communications which presented as postoperative biliary leakage found in 24
      (13.1%). Independent clinical predictors were alkaline phosphatase >133 U/L,
      total bilirubin levels >1.2 mg/dL, white blood cell count >10,000/mm(3) and cyst
      diameter >10 cm on multivariate analysis. Seventeen of 24 were low output biliary
      fistula which resolved spontaneously within 9.2 days. The remaining 7 were high
      output biliary fistula for which endoscopic sphincterotomy was performed in all
      patients, fistulas resolved within 22.6 days. Average interval between endoscopic
      sphincterotomy and fistula closure was 10.3 days. Mean hospital stay was longer
      in patients with biliary leakage than in those without (9.8 vs. 4.2 day p<0.001).
      There was no hospital mortality. CONCLUSION: The predictors demonstrated in this
      study should allow the likelihood of occult insidious cysto-biliary communication
      to be determined and, thus, indicate the need for additional procedures during
      operations to prevent the complications of biliary leakage.

PMID- 19573630
TI  - Assessment, surgeon, and society.
AB  - An increasing public demand to monitor and assure the quality of care provided by
      physicians and surgeons has been accompanied by a deepening appreciation within
      the profession of the demands of self-regulation and the need for accountability.
      To respond to these developments, the public and the profession have turned
      increasingly to assessment, both to establish initial competence and to ensure
      that it is maintained throughout a career. Fortunately, this comes at a time when
      there have been significant advances in the breadth and quality of the assessment
      tools available. This article provides an overview of the drivers of change in
      assessment which includes the educational outcomes movement, the development of
      technology, and advances in assessment. It then outlines the factors that are
      important in selecting assessment devices as well as a system for classifying the
      methods that are available. Finally, the drivers of change have spawned a number
      of trends in the assessment of competence as a surgeon. Three of them are of
      particular note, simulation, workplace-based assessment, and the assessment of
      new competences, and each is reviewed with a focus on its potential.

PMID- 19573631
TI  - Proteomic clues to the identification of QX disease-resistance biomarkers in
      selectively bred Sydney rock oysters, Saccostrea glomerata.
AB  - The Sydney rock oyster, Saccostrea glomerata, is susceptible to infection by the
      protozoan parasite, Marteilia sydneyi, the causative agent of QX disease. M.
      sydneyi infection peaks during summer when QX disease can cause up to 95%
      mortality. The current study takes a proteomic approach using 2-dimensional
      electrophoresis and mass spectrometry to identify markers of QX disease
      resistance among Sydney rock oysters. Proteome maps were developed for QX disease
      resistant and -susceptible oysters. Six proteins in those maps were clearly
      associated with resistance and so were characterized by mass spectrometry. Two of
      the proteins (p9 and p11) were homologous to superoxide dismutase-like molecules
      from the Pacific oyster, Crassostrea gigas, and the Eastern oyster, Crassostrea
      virginica. The remaining S. glomerata proteins had no obvious similarities to
      known molecules in sequence databases. p9 and p11 are currently being
      investigated as potential markers for the selective breeding of QX disease
      resistant oysters.

PMID- 19573632
TI  - History of amenorrhoea compromises some of the exercise-induced benefits in
      cortical and trabecular bone in the peripheral and axial skeleton: a study in
      retired elite gymnasts.
AB  - BACKGROUND: Female gymnasts frequently present with overt signs of
      hypoestrogenism, such as late menarche or menstrual dysfunction. The objective
      was to investigate the impact of history of amenorrhoea on the exercise-induced
      skeletal benefits in bone geometry and volumetric density in retired elite
      gymnasts. SUBJECTS AND METHODS: 24 retired artistic gymnasts, aged 17-36 years,
      who had been training for at least 15 h/week at the peak of their career and had
      been retired for 3-18 years were recruited. They had not been engaged in more
      than 2 h/week of regular physical activity since retirement. Former gymnasts who
      reported history of amenorrhoea ('AME', n=12: either primary or secondary
      amenorrhoea) were compared with former gymnasts ('NO-AME', n=12) and controls
      ('C', n=26) who did not report history of amenorrhoea. Bone mineral content
      (BMC), total bone area (ToA) and total volumetric density (ToD) were measured by
      pQCT at the radius and tibia (4% and 66%). Trabecular volumetric density (TrD)
      and bone strength index (BSI) were measured at the 4% sites. Cortical area (CoA),
      cortical thickness (CoTh), medullary area (MedA), cortical volumetric density
      (CoD), stress-strain index (SSI) and muscle and fat area were measured at the 66%
      sites. Spinal BMC, areal BMD and bone mineral apparent density (BMAD) were
      measured by DXA. RESULTS: Menarcheal age was delayed in AME when compared to NO
      AME (16.4+/-0.5 years vs. 13.3+/-0.4 years, p<0.001). No differences were
      detected between AME and C for height-adjusted spinal BMC, aBMD and BMAD, TrD and
      BSI at the distal radius and tibia, CoA at the proximal radius, whereas these
      parameters were greater in NO-AME than C (p<0.05-0.005). AME had lower TrD and
      BSI at the distal radius, and lower spinal BMAD than NO-AME (p<0.05) but they had
      greater ToA at the distal radius (p<0.05). CONCLUSION: Greater spinal BMC, aBMD
      and BMAD as well as trabecular volumetric density and bone strength in the
      peripheral skeleton were found in former gymnasts without a history of menstrual
      dysfunction but not in those who reported either primary or secondary
      amenorrhoea. History of amenorrhoea may have compromised some of the skeletal
      benefits associated with high-impact gymnastics training.

PMID- 19573633
TI  - Bone mass, size and previous fractures as predictors of prospective fractures in
      an osteoporotic referral population.
AB  - The influence of bone mass, bone size and previous low energy fractures upon
      prospective fractures has not been investigated in a referral osteoporotic
      population. We investigated the association between bone mass, bone size,
      previous fractures, body constitution, and prospective validated fractures in
      5701 women and 1376 men, aged 30 years and older. Bone mass measurements of the
      femoral neck were collected at a single study center in Sweden. Most of the
      subjects were measured on suspicion of osteoporosis. Data on validated low energy
      retrospective and prospective fractures in the cohort were collected from the
      corresponding health care district. Bone mineral density (BMD, g/cm(2)) and
      estimated volumetric BMD (vBMD, g/cm(3)) were shown to be good independent
      predictors for fracture in both women and men (Hazard ratio per standard
      deviation decrease (HR)=1.27-1.52, p<0.05). Bone size did not predict prospective
      fractures in either sex (HR=0.91-0.99, p>0.05), and bone size completely
      explained the higher BMD in men than in women. In women, retrospective low energy
      fractures (HR=1.78, p<0.001) and height (HR=1.02, p=0.006) were additional
      independent predictors of osteoporotic fractures after adjusting for age and BMD.
      In conclusion, we show that in a large osteoporotic referral population, age, BMD
      and previous fractures are independent predictors of prospective low energy
      fractures. These results add additional strength to the recent change in focus
      towards a multivariate analysis when assessing the future risk of fracture.

PMID- 19573634
TI  - In the zone: how a hepatocyte knows where it is.

PMID- 19573636
TI  - Bleeding rectal varices: trouble upstream?

PMID- 19573638
TI  - Live vaccination with an H5-hemagglutinin-expressing infectious laryngotracheitis
      virus recombinant protects chickens against different highly pathogenic avian
      influenza viruses of the H5 subtype.
AB  - Recently, we described an infectious laryngotracheitis virus (ILTV, gallid
      herpesvirus 1) recombinant, which had been attenuated by deletion of the viral
      dUTPase gene UL50, and abundantly expressed the hemagglutinin (HA) gene of a H5N1
      type highly pathogenic avian influenza virus (HPAIV) of Vietnamese origin. In the
      present study, efficacy of this vectored vaccine (ILTV-DeltaUL50IH5V) against
      different H5 HPAIV was evaluated in 6-week-old chickens. After a single ocular
      immunization all animals developed HA-specific antibodies, and were protected
      against lethal infection not only with the homologous HPAIV isolate
      A/duck/Vietnam/TG24-01/2005 (H5N1, clade 1, hemagglutinin amino acid sequence
      identity 100%), but also with heterologous HPAIV A/swan/Germany/R65/2006 (H5N1,
      clade 2.2, identity 96.1%) or HPAIV A/chicken/Italy/8/98 (H5N2, identity 93.8%).
      No symptoms of disease were observed after challenge with the H5N1 viruses, and
      only 20% of H5N2 challenged animals developed minimal clinical signs. Real-time
      RT-PCR analyses of oropharyngeal swabs revealed limited challenge virus
      replication, but the almost complete absence of HPAIV RNA from cloacal swabs
      indicated that no generalized infections occurred. Thus, unlike several previous
      vectors, ILTV-DeltaUL50IH5V was able to protect chickens against different HPAIV
      isolates of the H5 subtype. Vaccination with HA-expressing ILTV also allowed
      differentiation of immunized from AIV-infected animals by serological tests for
      antibodies against influenza virus nucleoprotein.

PMID- 19573637
TI  - Antibody persistence in UK pre-school children following primary series with an
      acellular pertussis-containing pentavalent vaccine given concomitantly with
      meningococcal group C conjugate vaccine, and response to a booster dose of an
      acellular pertussis-containing quadrivalent vaccine.
AB  - This open-label, randomised, controlled study examined antibody persistence
      following infant vaccination at 2, 3 and 4 months of age with either an acellular
      pertussis, diphtheria, tetanus, inactivated poliovirus, Haemophilus influenzae
      type b (DT(5)aP-IPV-Hib; Pediacel) or a whole-cell pertussis (DTwP//Hib+oral
      poliomyelitis vaccine [OPV]) combination vaccine, given concomitantly with
      meningococcal serogroup C conjugate (MCC) vaccine, followed by a Hib booster at
      approximately 15 months of age. Immune responses were sustained to 3.5-4.5 years
      of age for all antigens contained in Pediacel. Administration of an acellular
      pertussis-containing quadrivalent pre-school booster (Td(5)ap-IPV; Repevax), with
      or without measles, mumps and rubella (M-M-RII) vaccine, induced robust antibody
      responses indicative of protection, regardless of the vaccine used for the
      primary series. Reactogenicity of Repevax was acceptable and consistent with
      previous experience.

PMID- 19573639
TI  - The adjuvancy of OX40 ligand (CD252) on an HIV-1 canarypox vaccine.
AB  - The immunogenicity of current human immunodeficiency virus-1 (HIV-1) canarypox
      vaccines is weak and needs to be improved. Ligation of OX40 (CD134), a member of
      tumor necrosis factor receptor superfamily (TNFRSF), by its ligand OX40L (CD252),
      a tumor necrosis factor superfamily (TNFSF) molecule, has been demonstrated to
      provide a pivotal costimulatory signal to enhance CD4(+) T cell help of humoral
      and cytotoxic T cell immune responses. The present study examined whether an
      OX40L-expressing vector could boost the immunogenicity of the HIV-1 canarypox
      vaccine, vCP1452, in mice. Co-immunization of mice with OX40L-expressing
      canarypox and vCP1452 augmented HIV-1 specific CD8(+) T cell responses in terms
      of frequency and cytokine expression. OX40L-expressing canarypox enhanced the
      frequency of antigen specific CD8(+) T cells with an effector (CD127(-)CD62L(-))
      phenotype, which was associated with an ex vivo expansion of HIV-1 specific
      CD4(+) T cells. This was in contrast to our previous work in which a CD40L
      expressing construct preferentially enhanced antigen specific memory responses
      [Liu J, Yu Q, Stone GW, Yue FY, Ngai N, Jones RB, et al. CD40L expressed from the
      canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in
      mice and enhance the in vitro expansion of viral specific CD8+ T cell memory
      responses from HIV-1-infected and HIV-1-uninfected individuals. Vaccine
      2008;26(32):4062-72]. Surprisingly, OX40L did not enhance antibody responses
      elicited by the HIV-1 canarypox vaccine. We saw no added benefit by combining
      OX40L and CD40L vectors as an adjuvant strategy for vCP1452. Our results indicate
      that, similar to CD40L, canarypox vectors expressing OX40L can enhance the
      cellular but not humoral immunogenicity of HIV-1 canarypox vaccines. In summary,
      our findings show that OX40L can be used as a molecular adjuvant to enhance T
      cell immune responses.

PMID- 19573640
TI  - Identification of Setaria cervi heat shock protein 70 by mass spectrometry and
      its evaluation as diagnostic marker for lymphatic filariasis.
AB  - Using mass spectrometry and immunological approaches, a heat shock protein 70
      associated with lymphatic filariasis (LF) has been identified from a bovine
      filarial parasite Setaria cervi. A heat shock protein was detected in different
      life stages of S. cervi when exposed to an elevated temperature of 44 degrees C.
      A combination of ATP-agarose column chromatography and electro-elution was used
      for its purification from adult female extract. On closer examination, it
      migrated as a single band at 68 kDa on 10% SDS-PAGE. Peptide sequences
      TTPSYVAFTDTER, DSGAIAGLNVLR, IINEPTAAAIAYGLDK, NALESYAFNMK and LLSDFFSGK were
      obtained through MALDI-LC/MS analysis. Confirmation of peptides was accomplished
      by MASCOT database which showed substantial sequence homology with S. digitata,
      Wuchereria bancrofti, and Caenorhabditis elegans. Multiple sequence alignment
      using Clustal W showed 98% identity with W. bancrofti and only 28% with human
      HSP70. Furthermore, the antigenicity plot has shown that the highly antigenic
      amino acid residues are constituted within the conserved peptides. These
      observations suggest a plausible biological connection of ScHSP70 with the
      disease and its strong immunogenic nature. ScHSP70 showed antigenic cross
      reactivity with IgG class of antibody in different categories of filarial sera.
      However, when IgG subclasses were tested, IgG4 showed high specificity and
      sensitivity with asymptomatic microfilaraemic sera.

PMID- 19573641
TI  - Molecular modeling and epitopes mapping of human adenovirus type 3 hexon protein.
AB  - The hexon protein of human adenovirus (HAdV) processes type-specific B-cell
      neutralizing epitopes. We developed a new effective, reliable approach to map
      these epitopes on hexon protein of HAdVs. A three-dimensional (3D) model of the
      HAdV3 hexon was obtained by homology modeling and refined by molecular mechanics
      and molecular dynamics simulations. A modified evolutionary trace (ET) analysis
      called reverse ET (RET) was used to predict the type-specific B-cell neutralizing
      epitopes. An epitope-screening algorithm based on analyzing the solvent
      accessibility surface (SAS) area from the 3D model and calculation of sites
      homology using RET was designed and implemented in the BioPerl script language.
      Five epitope polypeptide segments were predicted and mapped onto the 3D model.
      Finally five polypeptides were synthesized and the predicted epitopes were
      identified by enzyme-linked immunosorbent assay (ELISA) and Neutralization Test
      (NT). It was found that the type-specific neutralizing epitopes of HAdV3 are
      located at the top surface of hexon tower regions (residue numbers: 135-146, 169
      178, 237-251, 262-272, 420-434). This work is of great significance to the
      molecular design of a multivalent HAdVs vaccine.

PMID- 19573642
TI  - Intragastric administration of attenuated Salmonella typhimurium harbouring
      transmissible gastroenteritis virus (TGEV) DNA vaccine induced specific antibody
      production.
AB  - Attenuated Salmonella typhimurium was selected as a transgenic vehicle for the
      development of live mucosal vaccines against transmissible gastroenteritis virus
      (TGEV). A 2.2kb DNA fragment, encoding for N-terminal domain glycoprotein S of
      TGEV, was amplified by RT-PCR and cloned into eukaryotic expression vector pVAX1.
      The recombinant plasmid pVAX-S was transformed by electroporation into attenuated
      S. typhimurium SL7207, the expression and translation of the pVAX-S delivered by
      recombinant S. typhimurium SL7207 (pVAX-S) was detected in vitro and in vivo
      respectively. BALB/c mice were inoculated orally with SL7207 (pVAX-S) at
      different dosages, the bacterium was safe to mice at dosage of 2x10(9)CFU and
      eventually eliminated from the spleen and liver at week 4 post-immunization. Mice
      immunized with different dosages of SL7207 (pVAX-S) elicited specific anti-TGEV
      local mucosal and humoral responses as measured by indirect ELISA assay.
      Moreover, the immunogenicity of the DNA vaccine was highly dependent on the
      dosage of the attenuated bacteria used for oral administration, 10(9)CFU dosage
      group showed higher antibody response than 10(8)CFU and 10(7)CFU dosages groups
      during week 4-8 post-immunization. The results indicated that attenuated S.
      typhimurium could be used as a delivery vector for oral immunization of TGEV DNA
      vaccine.

PMID- 19573643
TI  - Galactocele: an unusual cause of breast enlargement in children.
AB  - Galactoceles in children, either cystic or pseudotumors, are described in the
      literature as a rare cause of increasing breast size and can appear in males. We
      report a case of galactocele in a 15-month-old male, treated at our institution.
      The patient presented with a tumor in the right breast that had appeared 6 months
      earlier with no pain, signs of inflammation, or nipple secretion. Twelve cases
      found in the literature emphasize the importance of including galactocele in the
      differential diagnosis of benign breast masses in infancy.

PMID- 19573644
TI  - Primary vaginal calculus secondary to urethrovaginal fistula with imperforate
      hymen in a 6-year-old girl.
AB  - Primary vaginal stones are extremely rare in children and may be mistaken for
      bladder calculi on plain radiography. We present a case of a large vaginal
      calculus in a 6-year-old girl who had an imperforate hymen and urethrovaginal
      fistula. Hymenotomy and urethrovaginal fistula repair were performed, and the
      vaginal stone was extracted. It was postulated that the vaginal calculus
      originated from stasis of urine through the urethrovaginal fistula in the
      obstructed vagina. This is a unique case of a vaginal calculus with a congenital
      urethrovaginal fistula associated with an imperforate hymen.

PMID- 19573645
TI  - Slide tracheoplasty in infant with congenital tracheal stenosis and
      tracheomalacia after esophageal atresia with tracheoesophageal fistula repair.
AB  - Slide tracheoplasty can be applied successfully to all types of long segment
      congenital tracheal stenosis. In case of short segment tracheal stenosis, direct
      resection and anastomosis is often preferred. We report a case illustrating a new
      side benefit of the slide tracheoplasty in a patient presenting a relatively
      short hypoplastic tracheal segment coexisting with tracheomalacia after EA with
      TEF repair.

PMID- 19573646
TI  - Solid cervical ectopic thymus in an infant.
AB  - Cervical ectopic thymus presenting as a neck mass is rare in a neonate. Just more
      than 100 cases have been reported in the literature with less than 10% occurring
      in infants. We report a case of solid cervical ectopic thymus in an asymptomatic
      2-month-old boy. We review the literature and discuss the embryology,
      pathophysiology, diagnosis, and management of an infantile ectopic thymus.

PMID- 19573647
TI  - Conservative management of cervicomediastinal chyloma in an infant.
AB  - The accumulation of chyle into the mediastinum after surgical intervention is
      considered an extremely rare event, which has been previously described only in
      adulthood. We report on a 9-month-old boy who developed a cervicomediastinal
      chyloma after excision of a large left-sided supraclavicular cystic hygroma.
      Notwithstanding considerable tracheal deviation, the infant remained asymptomatic
      and was successfully treated by nonoperative treatment. Professionals should be
      aware of such an unusual condition, which may benefit from expectant management
      when evaluation establishes a high likelihood of clinical diagnosis, and
      patient's general condition remains stable. This approach may avoid, with little
      risk, unnecessary early surgical intervention in some of these patients.

PMID- 19573648
TI  - Caudate arterial branch bleeding: a rare complication after a Kasai
      portoenterostomy.
AB  - Massive bleeding from the porta hepatis is a rare complication after a Kasai
      portoenterostomy and usually requires urgent surgical intervention. Among the
      causes of the porta hepatis bleeding, bleeding from the injured caudate arterial
      branches has never been reported. Here, we describe 2 cases of caudate arterial
      branch bleeding after a Kasai portoenterostomy, which were successfully treated
      with transcatheter arterial embolization without laparotomy.

PMID- 19573649
TI  - Multifocal leiomyosarcomatosis in a 6-year-old child with epidermodysplasia
      verruciformis and immune defect.
AB  - Leiomyosarcoma and epidermodysplasia verruciformis are rarely encountered in
      children. The association of either leiomyosarcoma or epidermodysplasia
      verruciformis with immune deficiency has previously been documented. A 6-year-old
      girl, who has had multifocal leiomyosarcomatosis after the previous diagnoses of
      epidermodysplasia verruciformis and immune defect, represents an interesting
      association of these features.

PMID- 19573650
TI  - Noncommunicating isolated enteric duplication cyst in childhood.
AB  - Duplications of the alimentary tract are spherical or tubular structures lined by
      epithelium similar to intestine that are firmly attached to or share the wall of
      the alimentary tract and have a common blood supply with the adjacent segment of
      the bowel. Completely isolated duplication cysts are an extremely rare variety of
      gastrointestinal duplications with their own exclusive blood supply and do not
      communicate with the intestine. There are only 4 cases reported in the English
      literature-3 in childhood and 1 in an adult, and all are male. We report a case
      of noncommunicating isolated ileal duplication cyst in a 3-year-old female child
      that presented as a mass in the right iliac fossa, mimicking an intussusception.
      The duplication had its own blood supply arising from the terminal ileal
      mesentery. This report describes the first female patient with this condition and
      reviews the English literature.

PMID- 19573651
TI  - The Journal of Pediatric Surgery has a widely dispersed international readership,
      and over the years as Editor-in-Chief, I have enjoyed the vital support and
      valued counsel of a number of Editors representing various regions of the world.
      Editorial update 2009.

PMID- 19573652
TI  - Clinical and financial characteristics of pediatric surgery practices.
AB  - Pediatric surgical practices face many challenges. We wanted to define the
      clinical practice and financial support among different types of practices as
      follows: academic, private practice, and employed. METHODS: This study involved
      an Internet survey of members of the American Pediatric Surgical Association
      (APSA), comparisons using chi(2) and paired t test analyses. RESULTS: The
      response rate was 28.7% (233/811), 145 academic, 48 private, and 40 employed.
      More than 90% received partial to full financial hospital support. Only 7.3%
      received no outside support, most frequently those in private practices (16.7%; P
      = .016). More than 90% had resident or fellow coverage. Nearly all practices
      covered newborn conditions and solid tumors, with differences in pediatric
      trauma, patent ductus arteriosus, and urologic condition. Transfer out of
      community was low but increased for specific conditions during the respondents'
      absence, from 0.4% to 5.2% to 3.4% to 6.9% (P = .001-0.003). A minority of
      respondents noted that nonpediatric surgeons treated selected pediatric
      conditions in their communities as follows: inguinal hernia (38.4%), umbilical
      hernia (42.6%), abscesses (37.5%), and trauma (36.6%). Pediatric surgeons shared
      call within their group in 86.3%, whereas 5.6% took call alone. Many restricted
      call by excluding trauma (37.2%), soft tissue infections or appendectomies (21.3%
      for both), and older children (>12 years, 23.8%). Nearly one fifth (18.9%)
      expressed interest in having an APSA surgeon serve as a locum tenens in their
      practices. DISCUSSION: Many pediatric surgeons receive both financial and in-kind
      subsidies. Although they cover a wide breadth of surgical conditions, many limit
      the conditions that they treat to reduce call responsibilities. The workforce
      shortage in pediatric surgery creates call coverage problems that may affect up
      to 8% of US practices.

PMID- 19573653
TI  - Impaired somatic growth and delayed lung development in infants with congenital
      diaphragmatic hernia--evidence from a 10-year, single center prospective follow
      up study.
AB  - PURPOSE: In infants with congenital diaphragmatic hernia (CDH), somatic growth
      and pulmonary development are key issues beyond the time of intensive care
      treatment. The aim of the study was to investigate the somatic growth and
      pulmonary function after discharge and to compare CDH patients with a group of
      matched controls. METHODS: Anthropometric measurements and lung function tests
      were performed in 26 infants after surgical repair of CDH and 26 non-CDH
      intensive care patients, matched for gestational age and birth weight.
      Spontaneously breathing infants were tested at a mean of 44 weeks
      postconceptional age (range, 36-58 weeks). Body weight, body length, respiratory
      rate (RR), tidal volume (V(T)), functional residual capacity by body
      plethysmography (FRC(pleth)), respiratory compliance (C(rs)), and respiratory
      resistance (R(rs)) were measured. RESULTS: The mean (SD) weight gain per week in
      the CDH infants was significantly lower compared to non-CDH infants (89 [39] g vs
      141 [49] g; P = .002). The breathing pattern between both groups differed
      considerably. In CDH infants, V(T) was significantly lower (P < .001) and RR
      significantly higher (P = .005). The respiratory compliance was also
      significantly (P < .001) reduced, whereas R(rs) did not differ significantly. No
      statistically significant differences were seen in FRC(pleth) related to the body
      weight between CDH and non-CDH infants (20.3 [4.4] mL/kg vs 21.5 [4.9] mL/kg).
      CONCLUSION: Despite apparently well-inflated lungs after surgery, evidence of
      early and significantly reduced weight gain and impaired lung function in CHD
      patients should prompt careful dietary monitoring and regular lung function
      testing.

PMID- 19573654
TI  - Factors associated with survival in infants with congenital diaphragmatic hernia
      requiring extracorporeal membrane oxygenation: a report from the Congenital
      Diaphragmatic Hernia Study Group.
AB  - OBJECTIVE: To identify factors associated with survival in patients with
      congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane
      oxygenation (ECMO). METHODS: We retrospectively analyzed the data on 3100
      patients with CDH in the Congenital Diaphragmatic Hernia Study Group from 82
      participating pediatric surgical centers (1995-2004). Covariates considered
      included prenatal and perinatal clinical information, specifics of surgical
      repair, and the duration of extracorporeal support. RESULT: Nine hundred seven
      patients from the registry were identified as having been both managed with ECMO
      and undergone attempted surgical repair. The survival rate for the entire
      Congenital Diaphragmatic Hernia Study Group registry was 67% and 61% for those
      receiving ECMO in whom repair was attempted (P < .001). Among ECMO-treated
      children, survivors had a greater estimated gestational age (38 +/- 2 vs 37 +/- 2
      weeks; P < .01), greater birth weights (3.2 +/- 0.5 vs 2.9 +/- 0.5 kg; P < .001),
      were less often prenatally diagnosed (53% vs 63%; P < .01), and were on ECMO for
      a shorter period of time (9 +/- 5 vs 12 +/- 5 days; P < .001). In logistic
      regression models, therapy-related variables, including the duration of ECMO, the
      nature of diaphragmatic repair, and the type of abdominal closure and certain
      comorbidities, particularly the presence of a concomitant severe cardiac
      abnormality, were independently associated with outcome. CONCLUSION: Our model
      identifies a group of pre-surgical and postsurgical parameters that predict
      survival rate in patients with CDH on ECMO support. This model was derived from
      the retrospective data from a large database and will need to be prospectively
      tested.

PMID- 19573655
TI  - Presence of pneumomediastinum after blunt trauma in children: what does it really
      mean?
AB  - BACKGROUND: Pneumomediastinum after blunt thoracic trauma is often considered a
      marker of serious aerodigestive injury that leads to invasive testing. However,
      the efficacy of such testing in otherwise stable children remains unknown. We
      hypothesize that pneumomediastinum after blunt trauma in clinically stable
      children is rarely associated with significant underlying injury. METHODS: We
      reviewed all patients in our pediatric trauma database (1997-2007) for
      pneumomediastinum after blunt injury. Patients were then subdivided into 2
      groups: group I, isolated thoracic and group II, thoracic and additional
      injuries. Procedures and imaging were recorded, and outcomes were assessed.
      RESULTS: Thirty-two children with blunt thoracic trauma were included as follows:
      group I (n = 14) and group II (n = 18). In all patients, there were 28 diagnostic
      procedures performed resulting in only 1 positive test-a bronchial tear found on
      bronchoscopy in association with obvious respiratory distress. Group I was more
      than twice as likely to undergo invasive procedures as group II (P < .0001),
      resulting in significantly greater costs ($13683 +/- 2520 vs $5378 +/- 1000; P <
      .002). Patients in group I also received more diagnostic imaging to assess
      pneumomediastinum (1.89 vs 1.08 studies/patient per day; P < .05). More than 28%
      of all patients were completely asymptomatic and had pneumomediastinum as their
      only marker of injury. Strikingly, these patients received more than 46% of the
      procedures. CONCLUSIONS: Children with pneumomediastinum from blunt trauma often
      receive invasive and expensive testing with low yield, especially those with
      isolated thoracic trauma.

PMID- 19573656
TI  - Follow-up of surgical correction of aortic arch anomalies causing
      tracheoesophageal compression: a 38-year single institution experience.
AB  - OBJECTIVE: Anomalies of the aortic arch (vascular rings) are uncommon anomalies
      in which preferred strategies for diagnosis and treatment may vary among
      institutions. In this study, we report a description of our approach and review
      of our 38-year experience in patients surgically treated for vascular rings.
      METHODS: A retrospective review was conducted of all patients with/without
      symptomatic tracheoesophageal compression secondary to anomalies of the aortic
      arch and great vessels diagnosed from 1970 to 2008. A total of 183 patients
      underwent surgical repair. Median age at the time of the operation was 5 months
      (range, 3 days to 30 years). Patients were classified into 5 major subtypes based
      on their surgical anatomy as follows: right aortic arch-left ligamentum (n = 77),
      double aortic arch (n = 67), aberrant (retroesophageal) right subclavian artery
      (n = 30), pulmonary sling (n = 8), and innominate artery compression (n = 1). Six
      patients (3%) had an associated Kommerell diverticulum. In patients with a double
      aortic arch, 82% had a dominant right arch and 18% had a dominant left arch.
      Preoperatively, 80 patients (44%) had stridor, and 86 patients (47%) had
      recurrent upper respiratory tract infection. RESULTS: Associated cardiac
      diagnosis were present in 54 (30%) of 183 of all patients with vascular rings.
      Left thoracotomy was a common operative approach in all patients except pulmonary
      artery sling patients where a median sternotomy was the preferred approach. There
      were 3 early and 5 late deaths (all patients had complex cardiac anomalies) with
      a median follow-up of 6 years. Overall survival was 96% at 35 years.
      Postoperative complication occurred in 3 patients (2%) as follows: tracheostomy
      because of severe distal tracheal compression (n = 2) and left true vocal cord
      paralysis (n = 1). None of the patients showed any evidence of recurrent vascular
      ring anomalies at last follow-up. Of the children, 75% (135/180) were free from
      compressive symptoms within 1 year of the operation. CONCLUSIONS: Vascular
      anomalies with/without tracheoesophageal compression present symptomatically in a
      variety of ways, and noninvasive methods are used to identify the specific lesion
      and associated cardiac defects. Surgical repair is associated with low or no
      mortality in patients with uncomplicated complex of vascular anomalies.

PMID- 19573657
TI  - Does overgrowth of costal cartilage cause pectus excavatum? A study on the
      lengths of ribs and costal cartilages in asymmetric patients.
AB  - PURPOSE: The cause of pectus excavatum has been hypothesized to be overgrowth of
      the costal cartilage. According to this theory, the length of costal cartilages
      must be longer in the side of deep depression in asymmetric patients. To
      challenge this hypothesis, we measured the lengths of ribs and costal cartilages
      and investigated lateral differences. SUBJECTS AND METHODS: Twenty-four
      adolescent and adult patients with asymmetric pectus excavatum (14-30 years of
      age) with no history of surgery were investigated in this study. The fifth and
      sixth ribs and costal cartilages were individually traced to measure their full
      lengths on 3-dimensional computed tomographic (CT) images. As an index of
      asymmetry, sternal rotation angle was measured in the chest CT images. Patients
      with a 21 degrees or greater angle of sternal twist were designated as an
      asymmetric group and those with an angle of smaller than 20 degrees as a
      symmetric group. Lateral differences in the fifth and sixth costal and costal
      cartilage lengths were compared between the groups. RESULTS: On comparison of the
      costal and costal cartilage lengths in the asymmetric group, the right fifth ribs
      and costal cartilages were significantly shorter than the left (P = .02 and .03,
      respectively), and right sixth ribs were also significantly shorter than the left
      (P = .004), but right sixth costal cartilages were not (P = .31). In the
      symmetric group, the lengths of the left and right fifth ribs and costal
      cartilages were showing no significant difference (P = .20 and P = .80,
      respectively), and those of the sixth ribs and costal cartilage were also showing
      no significant difference (P = .97 and P = .64, respectively). DISCUSSION: The
      ribs and costal cartilages on the right side with severer depression were
      significantly shorter or not different than those on the contralateral side.
      Based on these findings, the theory of costal cartilage overgrowth is
      contradictory. The etiology of asymmetric chest deformity should be reevaluated.

PMID- 19573658
TI  - Liver nodules after portal systemic shunt surgery for extrahepatic portal vein
      obstruction in children.
AB  - BACKGROUND: Liver nodules have been reported after portal systemic shunt surgery
      (PSSS) in animal experiments or in humans with liver cirrhosis. The aim of our
      study was to assess the incidence of liver nodules after surgery for extrahepatic
      portal vein obstruction (EHPVO) in children without associated liver disease.
      METHODS: We retrospectively reviewed the charts of 45 children who had surgery
      from 1979 to 2005 for EHPVO in our institution, consisting of 38 PSSS and 7
      portal reperfusion procedures (PRPs). We assessed the presence of liver nodules
      on ultrasonography. RESULTS: Of 45 patients, 7 (15%) had liver nodules during a
      median of 80 months of follow-up. All the nodules occurred after PSSS. Five
      nodules were subjected to biopsy; we found 2 liver cell adenomas and 3 focal
      nodular hyperplasias. CONCLUSIONS: In this study, liver nodules occurred in 18%
      of cases after PSSS for EHPVO in children and not after PRP. As many children
      have undergone PSSS throughout the world, the presence of liver nodules should be
      considered during the follow-up of those patients.

PMID- 19573659
TI  - Histologic features of the portal plate in extrahepatic biliary atresia and their
      impact on prognosis--a Danish study.
AB  - BACKGROUND/PURPOSE: The aims of this study are as follows: METHOD: From 1979 to
      2003, 57 children have been operated by the Kasai procedure. Only 40 of these
      have had their portal plate removed for histologic examination. We divided the
      patients according to clinical outcome into a successful and a failure group and
      compared the histologic features of the portal plates in the 2 groups. Afterward,
      the portal plate histology from EHBA was compared with the porta hepatis area
      from patients dead from other causes. RESULTS: A significant difference between
      the success and the failure group was found with regard to the number of bile
      ducts, the maximal length measurable in any direction for bile duct structures,
      and the proliferation, but not for any type of diameter. The normal portal plate
      was different from the portal plate of children with biliary atresia by always
      having 2 large biliary structures and the cells being mucinous and columnar in
      the largest bile ducts. Only 1 of 4 normal portal plates showed signs of
      proliferation. There was no significant difference between the normal and the
      success group with respect to the number, maximal length, and proliferation of
      the bile ducts. A difference in the diameter between the normal group and the
      entire EHBA group was significant for the maximal internal diameter but not for
      the other types of diameter measurements. CONCLUSION: The present study shows the
      following:

PMID- 19573660
TI  - A single center 26-year experience with treatment of esophageal achalasia: is
      there an optimal method?
AB  - PURPOSE: Treatment modalities for achalasia are evolving and remain
      controversial. Herein, we report the relative efficacy and outcomes after
      dilatation or myotomy in children with achalasia. METHODS: A retrospective
      analysis of all children treated for achalasia at a tertiary center from 1981 to
      2007 was performed (n = 40). Demographics, presenting symptoms, perioperative
      parameters, and outcomes were analyzed using t tests and chi(2) statistics.
      RESULTS: Thirty patients were initially treated by esophageal dilatation (ED),
      whereas 10 were treated by laparoscopic or open Heller myotomy (HM). Both groups
      were similar with respect to age (10.6 vs 12.4 years; P = .19). There were 18
      males and 12 females in the ED group, compared to 5 males and 5 females in the HM
      group (P = .72). Mean duration of symptoms before diagnosis, including dysphagia,
      vomiting, food sticking, chest pain, and weight loss, was 15.9 months for ED and
      10.7 months for HM (P = .41). Mean time from diagnosis to initial intervention
      was 76 days in ED vs 86 days in HM (P = .78). Subsequent interventions by myotomy
      or both dilatation and myotomy were required in 9 (30%) of 30 patients in the ED
      group and 2 (20%) of 10 patients in the HM group (P = .70). A clear transition
      from open to laparoscopic approach occurred between 1995 and 2001. Mean operating
      times were comparable (186.3 vs 156.0 minutes; P = .48). Of 14 laparoscopic
      myotomies, 11 (79%) had fundoplication, and 2 (18%) of the 11 were converted to
      open procedure. Intraoperative mucosal perforation rates were similar between
      open and laparoscopic groups (17% vs 18%). At follow-up, 32% of ED patients vs
      43% HM had complete symptom relief (mean follow-up duration, 75.2 months; SD,
      196.5). CONCLUSION: Both dilatation and myotomy are effective immediate treatment
      of achalasia. A clear transition to and preference for laparoscopic approach has
      occurred in the treatment of achalasia in children.

PMID- 19573661
TI  - Minor and giant omphalocele: long-term outcomes and quality of life.
AB  - PURPOSE: Long-term outcome and quality of life in omphalocele (OC) studies are
      mainly focused on cosmetic disorders with the abdominal scar and gastrointestinal
      disorders. The aim of this study was to compare long-term mortality, morbidity,
      and quality of life between patients with minor and giant OCs. METHODS: Records
      of 89 minor and 22 giant OC children were reviewed. A questionnaire on general
      health was sent to all patients. A second questionnaire concerning quality of
      life and functional status; Darthmouth COOP Functional Health Assessment
      Charts/WONCA (COOP/WONCA) was sent to all patients aged 18 years or older and a
      peer control group. RESULTS: Of the surviving patients (69 minor OC, 20 giant
      OC), 12 were lost to hospital follow-up. The first questionnaire was returned by
      64 (83%) of 77 patients. There were no significant differences in
      gastrointestinal disorders. Cosmetic problems were experienced significantly more
      in giant OC. The results of the COOP/WONCA charts indicated a good to very good
      quality of life in both groups comparable to the control group. CONCLUSIONS: Our
      study indicates that after a high level of medical intervention perinatally,
      quality of life is good to very good in both groups and comparable to healthy
      young adults.

PMID- 19573662
TI  - Delivery of gastroschisis patients before 37 weeks of gestation is associated
      with increased morbidities.
AB  - BACKGROUND: Despite advances in the care of neonates with gastroschisis, patients
      present with significant morbidities. Preterm delivery of neonates with
      gastroschisis is often advocated to avoid the intestinal damage that may be
      sustained with prolonged exposure to amniotic fluid. However, preterm delivery
      may impose additional morbidities to this disease process. METHODS: We conducted
      a retrospective review of patients with gastroschisis born from 1989 to 2007.
      Demographic and clinical data were collected. Preterm healthy neonates, with
      gestational age from 26 to 36 weeks, were used as controls. RESULTS: Preterm
      infants with gastroschisis had a 14 times higher risk for any of the recorded
      morbidities. As compared to term neonates with gastroschisis, preterm neonates
      with gastroschisis had a higher rate of sepsis, longer duration to reach full
      enteral feedings, and longer length of stay. Although the preterm infants with
      gastroschisis were less likely to be small for gestational age at birth, they
      were as likely as the term infants with gastroschisis to have failure to thrive
      at discharge and had a greater drop in weight percentile during hospitalization.
      CONCLUSIONS: Preterm delivery should be avoided because there is no clear benefit
      to the gut in avoiding derivative injuries. Meticulous attention should be given
      to the nutritional needs of patients with gastroschisis.

PMID- 19573663
TI  - Evaluation of total oxidative and antioxidative status in pediatric patients
      undergoing laparoscopic surgery.
AB  - OBJECTIVE: Reactive oxygen species (ROS) induced by several diseases can trigger
      oxidative stress. During laparoscopy, increased intraabdominal pressure caused by
      pneumoperitoneum may lead to splanchnic ischemia followed by reperfusion because
      of deflation. Because ischemia reperfusion creates oxidative stress, in this
      study, we aimed to investigate the oxidative-antioxidative status of the
      pediatric patients with laparoscopic surgery. METHODS: The children underwent
      laparoscopic procedures under general anesthesia, and they were mechanically
      ventilated. Blood samples were obtained after induction of anesthesia, at the end
      of the surgery, and were centrifuged at 3000 revolutions per minute for 10
      minutes to separate plasma. The plasma total antioxidant status (TAS), total
      oxidant status (TOS), and oxidative stress index (OSI) were determined. RESULTS:
      Plasma TOS and OSI levels were significantly higher at the end of the surgery
      than after induction of anesthesia (P < .05 and P < .01, respectively). On the
      other hand, plasma TAS levels were lower in the end of the surgery than after
      induction of anesthesia (P < .05). CONCLUSIONS: These results suggest that ROS
      are generated during the laparoscopic procedure, possibly as a result of an
      ischemia-reperfusion phenomenon induced by the inflation and deflation of the
      pneumoperitoneum, which causes oxidative stress and consume plasma antioxidants.

PMID- 19573664
TI  - Ultrasound-guided percutaneous insertion of Hickman lines in children.
      Prospective study of 500 consecutive procedures.
AB  - AIM: The ultrasound-guided percutaneous technique of Hickman line insertion has
      not been widely adopted in pediatric surgical practice. We wished to review our
      own experience of using this technique for insertion into the internal jugular
      vein. METHODS: Our vascular access team consists of a consultant surgeon and 2
      consultant anesthetists. All procedures were prospectively recorded on a database
      and were either performed or directly supervised by our team. RESULTS: Five
      hundred consecutive Hickman lines were inserted between June 2004 and October
      2006. Patients' ages ranged from 14 days to 19 years (median, 44 months).
      Patients weighed between 600 g to more than 100 kg. Lines inserted were all
      tunneled silicone Hickman lines with a Dacron cuff (size 2.7F-10F, with 1-3
      lumens), of which 60% were 7F double-lumen lines. Successful cannulation occurred
      in 99.8%. Perioperative complications (within 30 days) occurred in 12 patients
      (2.4%) and were all treated conservatively with no need for either blood
      transfusion or chest drain. Catheter-related sepsis rate was 3.16 per 1000 line
      days. DISCUSSION: 1. The technique of ultrasound-guided percutaneous insertion of
      Hickman line to the internal jugular vein is safe and is applicable to all
      children regardless of size, age, or diagnosis. 2. Pediatric surgeons and
      anesthetists can learn this technique without specific training in interventional
      radiology. 3. A learning curve does exist, and we recommend concentrating
      pediatric vascular access procedures to a specialist team.

PMID- 19573665
TI  - Arteriovenous fistulas for hemodialysis access in children and adolescents using
      the proximal radial artery inflow site.
AB  - INTRODUCTION: Hemodialysis (HD) for children and adolescents with renal failure
      is increasingly common in the United States. Consensus opinion views an
      arteriovenous fistula (AVF) as the best long-term access option, although
      catheter-based HD remains the most common vascular access in children and has
      greater risks of complications and higher mortality rates than AVF access. This
      report reviews our experience with children and adolescents undergoing vascular
      access operations. METHODS: We reviewed 721 consecutive vascular access patients
      who had vascular access surgery by a single surgeon during the previous 5 years.
      Ten patients 20 years or younger were included in this study. In addition to
      physical examination, each patient had preoperative vascular ultrasound mapping
      by the operating surgeon. A radiocephalic AVF (RC-AVF) at the wrist was the first
      choice for dialysis access when feasible; however, the patients in this report
      were generally seen after years of intravenous access and venipunctures that
      necessitated more proximal AVF constructions. A proximal radial artery AVF (PRA
      AVF) was our most common choice for vascular access when an RC-AVF was not
      suitable. RESULTS: Patient ages were 9 to 20 years (mean, 16). Seven were male.
      Renal failure was caused by glomerulnephitis in 4 patients, 3 had a history of
      obstuctive uropathy, 2 were diabetic and one had congenital nephrotic syndrome.
      Eight patients had PRA-AVFs created, 1 had an RC-AVF, and 1 patient required a
      transposition AVF. Follow-up was 4 to 56 months (mean, 32 months). Primary,
      primary-assisted, and cumulative patencies were 77.8%, 100%, and 100% at 24
      months. No prosthetic grafts were used in any vascular access patient during the
      study period. CONCLUSION: We found HD access in children and adolescents was
      reliably established through use of a PRA-AVF when an RC-AVF was not feasible.
      Access sites were often possible through the upper arm cephalic veins and/or with
      retrograde flow into the forearm. Cumulative (secondary) patency was 100% at 24
      months.

PMID- 19573666
TI  - Interdisciplinary structural follow-up of surgical newborns: a prospective
      evaluation.
AB  - BACKGROUND: Information on physical and developmental outcomes of children with
      anatomical congenital anomalies (CAs) may indicate the need for early
      intervention and reduce impact on the child's life and parental burden. METHODS:
      From 1999 to 2003, 101 children with CA (76.5% of initial survivors) were seen 6
      monthly in a tertiary children's hospital. Growth, neurologic outcome, mental and
      psychomotor development as determined with the Bayley Scales of Infant
      Development, and categorization of predictive sociodemographic and medical
      variables of the children were evaluated prospectively and longitudinally.
      RESULTS: Congenital diaphragmatic hernia (CDH) and esophageal atresia patients
      showed impaired growth, that is, both height for age (-1.5 standard deviation
      score [SDS]) and weight for height (-1.0 SDS). Overall neurologic outcome was
      normal, however, suspect or abnormal for 40% of CDH patients. Overall mental
      development was normal, but psychomotor scores were significantly lower than the
      norm (95% confidence interval, 83.8-92.2 at 6 months and 87.9-98.5 at 24 months).
      Sex, maternal age, socioeconomic status, CA, severity-of-disease covariables, and
      need of medical appliances at home could predict negative outcome significantly
      (P < .05). CONCLUSIONS: The CA survivors show impaired growth and psychomotor
      developmental delay up to age 2 years. This warrants specific follow-up programs
      and infrastructure for these patients.

PMID- 19573667
TI  - Importance of psychological intervention for the recovery of children submitted
      to elective surgery.
AB  - PURPOSE: The effects of anxiety on the patient and his/her family are known to be
      the main factors that influence health recovery in child surgery. When the whole
      family can be prepared and supported by psychologic intervention, the damage to
      child behavior and family anxiety is attenuated. METHODS: This study was
      conducted in children between 2 and 6 years old, divided into 2 groups of 10
      pairs each. The experimental group received psychologic intervention, whereas the
      control group did not. One month after the surgery, they were reevaluated and
      compared with the same instruments used in the beginning of the study. The
      instruments used were as follows: the State-Trait Anxiety Inventory with the
      mothers and the Rutter's Child Behavior A2 Scale and the Posthospital Behavior
      Questionnaire with the children. RESULTS: The results were compared by the
      Wilcoxon and Mann-Whitney nonparametric tests for independent samples, both at
      the P < .05 significance levels. Mothers stated that anxiety was different in the
      postsurgery period, showing a significant decrease when comparing the
      experimental and control groups. Both instruments to measure child behavior also
      showed that prepared children had less habit changes than the control group,
      which showed increased levels of inadequate behavior. CONCLUSIONS: These data
      confirm reports in literature regarding child preparation before medical
      intervention and reinforces the importance of specialized presurgery planning
      procedures by the proper professional interfaced with the surgical colleagues,
      all aiming toward the best recovery for the children.

PMID- 19573668
TI  - Increased incidence of Hirschsprung's disease in patients with hypoplastic left
      heart syndrome--a common neural crest-derived etiology?
AB  - BACKGROUND: The enteric ganglions and the outflow tract of the heart originate
      from the neural crest. Impaired migration or differentiation of the neural crest
      cells causes Hirschsprung's disease (HD) and results in the development of
      cardiac outflow tract malformations. We hypothesize that the incidence of HD and
      bowel disorders associated with HD are increased in patients with hypoplastic
      left heart syndrome (HLHS) including left cardiac outflow tract obstruction.
      METHODS: All consecutive patients treated for HLHS at our institution during 1969
      to 2005 were retrospectively reviewed. The number of patients with histologically
      confirmed HD or clinical findings characteristic of HD such as constipation and
      delayed meconium were recorded from the patient records. RESULTS: A total of 113
      patients (65 males) were identified. At the time of survey, 57 patients (51%)
      were alive. Overall, there were 26 (23%) patients with constipation, and 9/23
      (39%) had delayed passage of meconium after 48 hours. Despite frequent bowel
      disorders only 4 (3.5%) patients had undergone histologic examination of the
      rectum. Hirschsprung's disease was detected in 3 patients (95% confidence
      interval, 0.62-8.77). The expected number of HD cases in the study population was
      0.026 giving 117-fold significant increase in the incidence of HD among patients
      with HLHS when compared to general Finnish population. CONCLUSIONS: The incidence
      of HD is increased in patients with HLHS. These results point to a common neural
      crest-derived embryologic origin of HD and HLHS and warrant further studies.

PMID- 19573669
TI  - Patterns of postoperative enterocolitis in children with Hirschsprung's disease
      combined with hypoganglionosis.
AB  - OBJECTIVE: The relationship between postoperative enterocolitis (EC) and
      Hirschsprung's disease (HD) combined with hypoganglionosis (HYP) has not been
      thoroughly reported elsewhere. The aim of this study was to investigate the
      incidence of EC after operation in children with HD combined with HYP and to
      identify new strategies to prevent postoperative EC. METHODS: From 1998 to 2005,
      97 children with HD underwent the modified Swenson's procedure in this institute.
      They were classified into 2 groups based on pathologic investigation as follows:
      group A contained 70 patients with HD and group B contained 27 patients with HD
      complicated with HYP. The mean follow-up time from the time of the operation was
      3.4 years (range, 1.5-8 years). The incidence of postoperative EC and anorectal
      functions were evaluated and compared between these 2 groups. RESULTS: Eight
      cases (11.4%) in group A developed postoperative EC, whereas 11 (40.7%) in group
      B did so. The incidence of postoperative EC in group A was significantly lower
      than that in group B (P < .005). According to the Rintala scoring system, the
      percentage of patients with an excellent score in group A (85.7%) was
      significantly higher than that in group B (P < .05). The recurrence rate of
      constipation in group B was 14.8% (4/27), whereas it was 2.8% (2/70) in group A.
      CONCLUSIONS: Postoperative EC is associated with retained proximal HYP, which
      suggests that HYP could be, at minimum, a predictive marker for this
      complication. Complete resection of HYP segment could potentially minimize the
      incidence of postoperative EC and alleviate the severity of EC.

PMID- 19573670
TI  - Fetal extraperitoneal rectal perforation: a rare neonatal emergency.
AB  - PURPOSE: Intraperitoneal bowel perforation may occur in utero as a result of a
      variety of abnormalities and typically results in sterile meconium ascites,
      pseudocysts, and/or calcification in the fetus. On the other hand,
      extraperitoneal bowel perforation in intrauterine life is extremely rare. The
      object of this report is to present our experience of prenatal extraperitoneal
      rectal perforation, defining the clinical presentation, management, and progress.
      METHODS AND MATERIALS: Nine babies who were identified from 2 centers in the
      Republic of South Africa with fetal extraperitoneal rectal perforation are
      presented. The details of these babies were obtained retrospectively from the
      case notes. RESULTS: All patients presented at or shortly after birth with air
      and meconium tracking below the pelvic floor manifesting as either an expanding,
      meconium-stained aerocele or with perirectal spreading sepsis. Where abdominal
      signs were present, laparotomy confirmed the extension of the meconium
      perforation into the peritoneal cavity. Management was by diverting colostomy,
      drainage of the perineal collection, and supportive therapy. A posterior approach
      to the rectum and excision of a fibrotic section of the lower rectal wall was
      performed in one case. One case developed rectal stenosis that was treated by
      dilatation before colostomy closure. In all the other cases, digital examination
      performed before colostomy closure ruled out significant narrowing. There was no
      mortality, and the site of the rectal perforation healed in all cases to leave
      good anorectal function after treatment. CONCLUSIONS: Fetal extraperitoneal
      perforation is extremely rare, but the clinical features are easily recognizable,
      and when appropriate therapy is instituted, the outcome is likely to be good with
      normal anorectal function to be expected in the long-term. The exact cause of the
      condition is unknown.

PMID- 19573671
TI  - Outcomes in pediatric patients undergoing straight vs J pouch ileoanal
      anastomosis: a multicenter analysis.
AB  - BACKGROUND: Outcomes remain controversial for patients undergoing straight (SIAA)
      vs J pouch (JPAA) ileoanal anastomosis, particularly in children where fewer such
      cases are performed. Our 3 centers have had extensive experience with both
      techniques. Thus, we had the unique opportunity to compare outcomes within the
      same centers. METHODS: We retrospectively analyzed 250 children after
      proctocolectomy with either SIAA or JPAA, for the first 3 years after pull
      through. A functional stooling score was developed to further assess outcomes.
      Data were analyzed using chi(2) tests and generalized linear mixed models for
      repeated measures. RESULTS: Two hundred three patients had sufficient data for
      complete analysis (42% males; mean surgery age, 15 +/- 7years). Surgical
      indications were ulcerative colitis (168) and familial adenomatoid polyposis
      (35). Surgical procedures included SIAA (112) and JPAA (91). Daytime and
      nighttime stooling frequencies were significantly higher (P < .013) for SIAA
      patients at 1 to 24 months after pull-through; however, stooling frequencies
      began approximating each other by this time. Symptomatic pouchitis (compared to
      enteritis after SIAA) was significantly higher in JPAA patients (odds ratio, 4.5;
      confidence interval, 2.32-8.72). Frequency of pouchitis declined with time. There
      was no significant difference in the incidence of surgical complications between
      the 2 groups. Finally, continence rates were strikingly good in both groups
      compared to previously reported series. CONCLUSION: Straight ileoanal anastomosis
      and JPAA are associated with considerable morbidity; SIAA has higher stool
      frequency and JPAA has increased pouchitis. Over time, we found that problems
      improved, and functional stooling scores became similar. JPAA had consistently
      lower stool frequency and better continence rates; however, these differences
      were small and may have minimal clinical significance. In addition, such
      differences need to be balanced against the high rate of pouchitis with JPAA.
      Continence was excellent regardless of the technique.

PMID- 19573672
TI  - A prospective, randomized comparison of skin adhesive and subcuticular suture for
      closure of pediatric hernia incisions: cost and cosmetic considerations.
AB  - PURPOSE: In this study, we compared the skin adhesive 2-octylcyanoacrylate to
      subcuticular suture for closure of pediatric inguinal hernia incisions to
      determine if skin adhesive improves wound cosmesis, shortens skin closure time,
      and lowers operative costs. METHODS: We prospectively randomized 134 children
      undergoing inguinal herniorrhaphy at our institution to have skin closure with
      either skin adhesive (n = 64) or subcuticular closure (n = 70). Data collected
      included age, sex, weight, type of operation, total operative time, and skin
      closure time. Digital photographs of healing incisions were taken at the 6-week
      postoperative visit. The operating surgeon assessed cosmetic outcome of incisions
      using a previously validated visual analog scale, as well as an ordinate scale. A
      blinded assessment of cosmetic outcome was then performed by an independent
      surgeon comparing these photographs to the visual analog scale. Operating room
      time and resource use (ie, costs) relative to the skin closure were assessed.
      Comparisons between groups were done using Student's t tests and chi(2) tests.
      RESULTS: Children enrolled in the study had a mean +/- SE age of 3.7 +/- 0.3
      years and weighed 16 +/- 0.8 kg. Patients were predominantly male (82%). Patients
      underwent 1 of 3 types of open hernia repair as follows: unilateral herniorrhaphy
      without peritoneoscopy (n = 41; 31%), unilateral herniorrhaphy with
      peritoneoscopy (n = 55; 41%), and bilateral herniorrhaphy (n = 38; 28%). Skin
      closure time was significantly shorter in the skin adhesive group (adhesive = 1.4
      +/- 0.8 minutes vs suture = 2.4 +/- 1.1 minutes; P = .001). Mean wound cosmesis
      scores based on the visual analog scale were similar between groups (adhesive =
      78 +/- 21; suture=78 +/- 18; P = .50). Material costs related to herniorrhaphy
      were higher for skin adhesive (adhesive = $22.63 vs suture = $11.70; P < .001),
      whereas operating room time costs for adhesive skin closure were lower (adhesive
      = $9.33 +/- 5.33 vs suture = $16.00 +/- 7.33; P < .001). Except for a 7%
      incidence of erythema in both groups, there were no complications encountered.
      CONCLUSIONS: There is no difference in cosmetic outcome between skin adhesive and
      suture closure in pediatric inguinal herniorrhaphy. Material costs are increased
      because of the high cost of adhesive relative to suture. This is partially
      offset, however, by the cost savings from reduction in operating room time.

PMID- 19573673
TI  - Looking past the lump: genetic aspects of inguinal hernia in children.
AB  - Inguinal hernia is associated with a multitude of genetic syndromes. Disorders of
      the microfibril, elastin, collagen, and the glycosaminoglycan component of the
      extracellular matrix can result in an increase in the likelihood of inguinal
      hernia. In addition, inguinal hernia may be the presenting feature of disorders
      of sexual differentiation. Inguinal hernia of unknown etiology also occurs more
      commonly in several other groups of genetic diseases including chromosomal
      disorders, microdeletion disorders such as 22q11.2 microdeletion, and in single
      gene disorders. We review the genetics of connective tissue formation and focus
      on a series of genetic conditions that may present with or are characterized by a
      higher risk of inguinal hernia. A comprehensive review of the literature aims to
      provide a diagnostic framework to aid in the identification of patients with
      inguinal hernia as part of underlying genetic disease.

PMID- 19573674
TI  - Management of congenital fourth branchial arch anomalies: a review and analysis
      of published cases.
AB  - BACKGROUND/PURPOSE: Congenital fourth branchial arch anomalies are uncommon
      entities, heretofore described only in case reports, affecting primarily
      children, and typically presenting as a cervical inflammatory process. The aim of
      the study was to collect appropriate data on the diagnosis, treatment, and
      outcome of this condition and to suggest guidelines for its management. METHODS:
      We conducted a structured review of the literature for cases explicitly
      identified as congenital fourth branchial arch anomalies or meeting anatomical
      criteria for this condition. We computed descriptive statistics and performed
      several post hoc 2-way comparisons of subgroups of cases. RESULTS: We located and
      critically evaluated 526 cases. Fourth arch anomalies were usually located on the
      left (94%) and generally presented as acute suppurative thyroiditis (45%) or
      recurrent neck abscess (42%). Barium swallow and direct laryngoscopy were the
      most useful diagnostic tools. Treatment options differed mainly in recurrence
      rates: incision and drainage, 89%; open neck surgery and tract excision, 15%;
      endoscopic cauterization of the sinus tract opening, 15%; and open neck surgery
      with partial thyroidectomy, 8%. Complications after surgery occurred primarily in
      children 8 years or younger. CONCLUSION: Fourth arch anomalies are more common
      than once thought. Treatment of these disorders with repeated incision and
      drainage yields high rates of recurrence; thus, complete excision of the entire
      fistula tract during a quiescent period appears preferable. Combining this
      surgery with partial thyroidectomy may further decrease recurrence rates.
      Complications can likely be minimized by using antibiotic treatment of acute
      infections or endoscopic cauterization in children 8 years or younger, and
      delaying open neck surgery.

PMID- 19573675
TI  - Gastric tube-pericardial fistula: a remote complication of esophageal replacement
      for long gap esophageal atresia.
AB  - Several short and long-term complications of esophageal replacement have been
      described in the literature. We report the case of a gastric tube-pericardial
      fistula occurring 20 years after initial repair of long gap esophageal atresia
      with a reversed gastric tube.

PMID- 19573676
TI  - Malignant epithelioid hemangioendothelioma of the bladder: the first case report
      in a child.
AB  - Epithelioid hemangioendothelioma is a distinct vascular tumor, which is very rare
      in the bladder. To the best of our knowledge, only one adult patient has been
      reported so far in the English literature. A 4-year-old boy with a huge bladder
      mass, with the pathologic diagnosis of epithelioid hemangioendothelioma, is the
      first patient with this lesion described in the pediatric age-group.

PMID- 19573677
TI  - Abdominal pain and wandering spleen in young children: the importance of an early
      diagnosis.
AB  - PURPOSE: The aim of the study is to increase clinical awareness of torsion of
      wandering spleen (WS) in childhood and the need of a rapid diagnosis. METHODS:
      Four cases operated for torsion of WS are retrospectively reviewed. Ages at
      presentation were, respectively, 30 months, 5 years, 4 years, and 3 years,
      without sex preference. All subjects led a history of abdominal pain and a mass
      on physical examination. RESULTS: Torsion of WS should be suspected in any child
      presenting with acute abdomen. Moreover, in case of acute abdomen and
      intermittent abdominal pain, we suggest studying spleen position with ultrasound.
      CONCLUSIONS: Ultrasonography with color Doppler is the best choice for diagnosis
      of torsion of WS. Computed tomography is a good complementary examination, but it
      needs to submit young patients to a general anesthesia and delays an emergency
      situation.

PMID- 19573678
TI  - Removal of a sewing needle from an occult esophageal ingestion in a 9-month-old.
AB  - A healthy 9-month-old boy presented with a 1-month history of cough. A chest x
      ray showed a linear metallic foreign body (FB) lying transversely in the
      posterior mediastinum. Computed tomographic scan confirmed the location and size
      of the metallic FB and also revealed a large pericardial effusion that was
      corroborated by echocardiogram. The patient underwent a right thoracotomy
      revealing a normal esophagus without mediastinitis and a 12-mm needle in the
      posterior mediastinum embedded in the pericardium with the sharp end abutting the
      left atrium. The needle was extracted uneventfully, and his postoperative course
      was unremarkable. The diagnosis and treatment for this case are discussed along
      with a review of the literature.

PMID- 19573679
TI  - Aortopexy for persistent tracheal obstruction after double aortic arch repair.
AB  - Persistent respiratory symptoms often occur after double aortic arch (DAA) repair
      but rarely require a second operation. We report 4 children with severe
      respiratory problems (failure to extubate, 2; severe respiratory distress, 2)
      caused by severe tracheomalacia and tracheal compression after DAA repair,
      treated by anterior aortopexy. Aortopexy proved effective and safe in improving
      symptoms and provides a simple treatment option for children with severe malacia
      or tracheal compression after DAA repair.

PMID- 19573680
TI  - Plexiform schwannoma of the esophagus in a child with neurofibromatosis type 2.
AB  - Schwannoma is a benign neoplasia of the peripheral nerve sheath. Its localization
      in the gastrointestinal tract, and in particular in the esophagus, is very rare.
      According to the existing literature esophageal schwannoma has been reported so
      far only in adult patients. We report the case of an 11 year old patient with
      neurofibromatosis, type 2, who underwent surgical excision of a plexiform
      schwannoma of the esophagus.

PMID- 19573681
TI  - Ileal duplication cyst: Y-configuration on in vivo sonography.
AB  - Although the double wall or muscular rim sign is considered to be a
      characteristic sonographic imaging finding of an enteric duplication cyst, this
      sign can also be produced by Meckel's diverticulum and sonographic artifacts. The
      Y-configuration on in vitro sonography has been reported to be useful for the
      definitive diagnosis of an enteric duplication cyst. Here, we report a case of an
      intraoperatively confirmed ileal duplication cyst that was correctly diagnosed
      before by identification of the Y-configuration on in vivo sonography.

PMID- 19573682
TI  - A new technique to remove a "stuck" totally implantable venous access catheter.
AB  - Removal of a totally implantable venous access device (port) is usually a simple
      procedure; however, if a catheter has been in place for a very long period, it
      may adhere firmly to the vessel wall. We report a new technique to facilitate
      removal of a stuck catheter. A 16-year-old girl was admitted for removal of her
      port, which had been inserted for chemotherapy 11 years earlier. After her
      disease was controlled, the catheter could not be pulled out during surgery. To
      remove the catheter, we inserted a guidewire to straighten the catheter and then
      applied a "push-in" force to detach the adherence from the central vein. The
      catheter was then removed successfully. We believe that this is a new and simple
      method for removing a "stuck" catheter.

PMID- 19573683
TI  - Omphalocele: how big does it have to be a giant one?

PMID- 19573686
TI  - Contrast enema for pediatric intussusception: is reflux into the terminal ileum
      necessary for complete reduction?

PMID- 19573688
TI  - Annual review of selected scientific literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 19573687
TI  - The effect of immediate dentin sealing on the marginal adaptation and bond
      strengths of total-etch and self-etch adhesives.
AB  - STATEMENT OF PROBLEM: Sealing ability and bond strengths of total-etch and self
      etch dentin adhesives used for immediate dentin sealing have not been assessed
      and established. PURPOSE: The purpose of this study was to determine the
      effectiveness of immediate dentin sealing (IDS) using total-etch or self-etch
      dentin adhesives on microleakage and microtensile bond strength. MATERIAL AND
      METHODS: Twenty recently extracted molars were selected, and standard MOD inlay
      preparations were made with the gingival margins located below the cemento-enamel
      junction. The teeth were assigned to 4 experimental groups (n=5) according to the
      indirect composite restoration cementation technique used: (1) immediate dentin
      sealing with Adper Single Bond (TEBI); (2) conventional adhesive cementation
      technique using Adper Single Bond (TEAI); (3) immediate dentin sealing using
      Adper Prompt L-Pop (SEBI); or (4) conventional adhesive cementation technique
      using Adper Prompt L-Pop (SEAI). The restored teeth were thermal cycled 1,000
      times between 5 degrees and 55 degrees C and then immersed in 50% ammoniacal
      silver nitrate. Three specimens per restoration were evaluated for microleakage,
      according to predefined scores, and submitted to Friedman's test (alpha=.05). The
      specimens were then sectioned to obtain 0.8 +/-0.2-mm-thick sticks (with n
      ranging from 32 to 57 specimens) and submitted to microtensile bond strength
      (muTBS) testing. The obtained data were submitted to 2-way ANOVA test
      (alpha=.05). RESULTS: None of the experimental groups demonstrated complete
      elimination of marginal microleakage. There were significant differences in
      microleakage of the tested adhesives (P>.001). IDS microleakage scores were
      similar to those obtained using the conventional cementation technique (CCT) for
      both adhesives. The highest mean bond strengths were obtained with TEBI (51.1
      MPa), whereas SEAI showed the lowest mean bond strengths (1.7 MPa). IDS resulted
      in significantly higher bond strengths than CCT (P<.001). CONCLUSIONS: Total-etch
      and self-etch adhesives have a significant effect on IDS. IDS resulted in high
      bond strengths for both adhesives; however, the microleakage was similar to that
      obtained with CCT. (J Prosthet Dent 2009;102:1-9).

PMID- 19573689
TI  - An implant-supported, cobalt-chromium milled bar and nonflanged attachment
      retained overdenture to rehabilitate the edentulous mandible.
AB  - Rehabilitation of the edentulous mandible has been revolutionized by the use of
      osseointegrated endosteal implants. One treatment option for such rehabilitation
      is an implant-supported bar and overdenture. This article presents a procedure
      for the fabrication of an implant-supported, cobalt-chromium milled bar and
      nonflanged attachment-retained overdenture. The prosthesis described meets
      requirements for masticatory efficiency, natural esthetics, and maintenance of
      the health of residual tissues. The biological and mechanical considerations of
      the design, and the advantages, disadvantages, and contraindications of the
      prosthesis are discussed. (J Prosthet Dent 2009;102:46-51).

PMID- 19573690
TI  - A method to make a preliminary impression of mobile teeth.

PMID- 19573691
TI  - A method of removing a splint material from a cast with minimal damage.

PMID- 19573692
TI  - A device to hold implant abutments for extraoral preparations.

PMID- 19573693
TI  - Technique for controlling the cement for an implant crown.

PMID- 19573694
TI  - [Ocular toxicity, bisphosphonate and Paget disease].

PMID- 19573695
TI  - Cytoplasmic pH measurement and homeostasis in bacteria and archaea.
AB  - Of all the molecular determinants for growth, the hydronium and hydroxide ions
      are found naturally in the widest concentration range, from acid mine drainage
      below pH 0 to soda lakes above pH 13. Most bacteria and archaea have mechanisms
      that maintain their internal, cytoplasmic pH within a narrower range than the pH
      outside the cell, termed "pH homeostasis." Some mechanisms of pH homeostasis are
      specific to particular species or groups of microorganisms while some common
      principles apply across the pH spectrum. The measurement of internal pH of
      microbes presents challenges, which are addressed by a range of techniques under
      varying growth conditions. This review compares and contrasts cytoplasmic pH
      homeostasis in acidophilic, neutralophilic, and alkaliphilic bacteria and archaea
      under conditions of growth, non-growth survival, and biofilms. We present diverse
      mechanisms of pH homeostasis including cell buffering, adaptations of membrane
      structure, active ion transport, and metabolic consumption of acids and bases.

PMID- 19573697
TI  - Biology and genomic analysis of Clostridium botulinum.
AB  - The ability to form botulinum neurotoxin is restricted to six phylogenetically
      and physiologically distinct bacteria (Clostridium botulinum Groups I-IV and some
      strains of C. baratii and C. butyricum). The botulinum neurotoxin is the most
      potent toxin known, with as little as 30-100 ng potentially fatal, and is
      responsible for botulism, a severe neuroparalytic disease that affects humans,
      animals, and birds. In order to minimize the hazards presented by the botulinum
      neurotoxin-forming clostridia, it is necessary to extend understanding of the
      biology of these bacteria. Analyses of recently available genome sequences in
      conjunction with studies of bacterial physiology are beginning to reveal new and
      exciting information on the biology of these dangerous bacteria. At the whole
      organism level, substantial differences between the six botulinum neurotoxin
      forming clostridia have been reported. For example, the genomes of proteolytic C.
      botulinum (C. botulinum Group I) and non-proteolytic C. botulinum (C. botulinum
      Group II) are highly diverged and show neither synteny nor homology. It has also
      emerged that the botulinum neurotoxin-forming clostridia are not overtly
      pathogenic (unlike C. difficile), but saprophytic bacteria that use the
      neurotoxin to kill a host and create a source of nutrients. One important feature
      that has contributed to the success of botulinum neurotoxin-forming clostridia is
      their ability to form highly resistant endospores. The spores, however, also
      present an opportunity to control these bacteria if escape from lag phase (and
      hence growth) can be prevented. This is dependent on extending understanding of
      the biology of these processes. Differences in the genetics and physiology of
      spore germination in proteolytic C. botulinum and non-proteolytic C. botulinum
      have been identified. The biological variability in lag phase and its stages has
      been described for individual spores, and it has been shown that various adverse
      treatments extend different stages of lag phase. For example, heat treatment
      primarily extended germination, while incubation at a chilled temperature
      primarily extended outgrowth. The neurotoxin gene is present within a cluster of
      associated genes, and can be located on the chromosome, a plasmid or a
      bacteriophage. Two basic types of neurotoxin cluster have been identified.
      Evolution of the neurotoxin gene and cluster has occurred independently of the
      organism, and involved a series of recombination events but is still poorly
      understood. Factors affecting the regulation of neurotoxin formation also remain
      poorly understood, and will be the focus of much future research.

PMID- 19573698
TI  - Advanced cytoreductive surgery in gynecologic oncology.

PMID- 19573699
TI  - Surgical program building in advanced ovarian cancer: European perspective.
AB  - The majority of ovarian cancer patients are diagnosed with advanced-stage
      disease, for which standard treatment consists of cytoreductive surgery and
      platinum-based chemotherapy. As the maximum diameter of residual disease at the
      end of cytoreductive surgery is one of the most important prognostic factors,
      chances to achieve complete debulking of tumor should be optimized. Therefore,
      cytoreductive surgery is best performed in an expert center. To establish such an
      expert center, not only surgical skills and experience are needed. High quality
      surgical care is delivered by a multidisciplinary team of, among others, oncology
      nurses, anesthesiologists, pathologists, dieticians and physiotherapists.
      Furthermore, expert centers typically deliver comprehensive cancer care,
      including expertise in radiotherapy and chemotherapy, palliative care and patient
      support. Development and implementation of a surgical program aiming at
      establishing an expert center for cytoreductive surgery involves careful
      assessment of the pre-program pattern of care, training of care providers,
      establishment of a multidisciplinary team and referral pathway, availability of
      sufficient resources and infrastructure and a monitoring and quality assurance
      plan. The aim of this paper is to give guidance in programmatic development of an
      expert center for advanced ovarian cancer surgery from a European perspective.

PMID- 19573700
TI  - Advanced cytoreductive surgery: Asia Pacific perspective.
AB  - The thoroughness of cytoreductive surgery is the largest contributor to survival
      for patients with advanced ovarian and primary peritoneal carcinoma. For many
      years the surgery undertaken by Gynaecologic Oncologists has been tailored to
      match their surgical training. Future surgical training of Gynaecologic
      Oncologists needs to be tailored to the surgery required to provide complete
      tumour removal to no residual disease. This means the better teaching of anatomy
      and an increased scope of surgery to include the general and upper abdominal
      procedures and management required. This paradigm shift will be a challenge for
      all and impossible for some. It will require a significant mind-shift not only
      from our craft group and the profession at large but especially from the
      speciality Colleges who will need to take these changes on board for future
      curriculum development. The development of Advanced Cytoreductive Surgical Units
      needs to be undertaken in a team environment. This requires a commitment from
      participants at all levels, from the lead oncology surgeon through the hospital
      administration to the support services involved. While advanced cytoreductive
      surgery is feasible, it is only in this team environment, limited to major
      multidisciplinary hospitals, that it can be safely achieved by meticulous
      attention to detail at all levels.

PMID- 19573701
TI  - Minimally invasive surgery in gynecologic oncology.

PMID- 19573702
TI  - Emergence of robotic assisted surgery in gynecologic oncology: American
      perspective.
AB  - OBJECTIVES: To discuss the emergence of robotic surgery in gynecologic oncology
      and describe the growth of robotic surgery in a university medical center and a
      community based practice. METHODS: In addition to the historical evolution of the
      robotic assisted surgery medicine, a survey of robotic cases was performed on two
      robotic programs since the inception of the programs. A review of the current
      literature on the use of the da Vinci robot in gynecologic oncology was also
      performed. RESULTS: The robotic surgery programs at UNC Hospital and Florida
      Hospital are growing steadily since the inception of the programs in 2005 and
      2006, respectively. Since 2005 there have also been numerous publications
      detailing the effectiveness, safety, and efficiency of the robot. CONCLUSIONS:
      Robotic surgery is gaining acceptance and is rapidly growing as evidenced by an
      increased number of publications on the topic; these publications demonstrate the
      safety, efficacy, and improved outcomes compared to open surgery and conventional
      laparoscopy.

PMID- 19573703
TI  - Advanced cytoreductive surgery: American perspective.
AB  - Over the past 3 to 4 decades a special knowledge and understanding of the
      pathophysiology and behavior of gynecologic peritoneal surface malignancies has
      led to a significant improvement of the relevant treatment modalities, mirroring
      advances in chemotherapy approaches and improved knowledge of tumor biology. The
      surgical management of advanced ovarian, primary peritoneal, and fallopian tube
      cancers has evolved from the performance of basic gynecologic procedures to the
      incorporation of more comprehensive surgical procedures. This extensive surgical
      approach is of great importance for estimating the prognosis and guiding further
      treatment of affected patients. These complex procedures involving multi-organ
      resections are generally long and require excellent knowledge of upper abdominal
      anatomy. This article will focus on the role and program development of advanced
      cytoreductive surgery in patients with gynecologic peritoneal malignancies. This
      review is an attempt to provide guidance for the rationale and strategic approach
      to develop the surgical skill set, meet institutional requirements, and implement
      the concept of a comprehensive cytoreductive surgical team.

PMID- 19573704
TI  - Indications and teaching of fertility preservation in the surgical management of
      gynecologic malignancies: European perspective.
AB  - Young women affected by a malignant tumor have to cope, after the announcement of
      diagnosis, with the treatment and its secondary effects. Indeed, some of them may
      definitively impact on their fertility potential. Especially in pelvic tumors,
      treatments are more or less mutilating, either by a direct surgical resection of
      pelvic organs or by destruction of their functioning after chemotherapy or
      radiation therapy. Surgeons are often at the front line in the management of
      gynecologic tumors. It is important for them to be aware not only of the surgical
      techniques currently available to preserve fertility, but as well of their
      indications and limits, according to the tumor type or its treatment. This
      knowledge will enable them to deliver fair information to the patient or couple,
      keeping in mind that, multidisciplinarity is of a paramount importance and
      referring a patient to a more experienced team, is sometimes the best solution.
      Through a literature review, we report on the most recent results of the
      different options available today according to cancer localization as well as
      some opinions concerning indications, management, organization of care, and
      teaching of these techniques.

PMID- 19573705
TI  - A model program for radical hysterectomy for cervical cancer: Asia Pacific
      perspective.
AB  - Laparoscopic surgery for gynecological oncology is an important progress in the
      combination of scientific, technological and surgical techniques, which not only
      enhanced the efficacy of surgical treatment of gynecological oncology, but also
      is superior to conventional open surgery with regard to postoperative mental
      rehabilitation in gynecological oncology patients. But it is not without its
      risks and complications. There are still several new challenges on both theory
      and surgical skill improvement to be overcome. Firstly, to form a laparoscopic
      surgical team, there are a lot of special requirements of both the team members
      and the equipment which restrict the popularization of the laparoscopic radical
      hysterectomy. Secondly, every detail should be taken into careful consideration
      and the risks should be balanced and benefits ascertained before performing the
      laparoscopic procedures. So, for the development of minimally invasive surgery,
      we should be accumulating the clinical experiences, improving the laparoscopic
      skills and normalizing and certifying training centers, and verifying the long
      term surgical effects by evidence-based medicine.

PMID- 19573696
TI  - Physiology of mycobacteria.
AB  - Mycobacterium tuberculosis is a prototrophic, metabolically flexible bacterium
      that has achieved a spread in the human population that is unmatched by any other
      bacterial pathogen. The success of M. tuberculosis as a pathogen can be
      attributed to its extraordinary stealth and capacity to adapt to environmental
      changes throughout the course of infection. These changes include: nutrient
      deprivation, hypoxia, various exogenous stress conditions and, in the case of the
      pathogenic species, the intraphagosomal environment. Knowledge of the physiology
      of M. tuberculosis during this process has been limited by the slow growth of the
      bacterium in the laboratory and other technical problems such as cell
      aggregation. Advances in genomics and molecular methods to analyze the M.
      tuberculosis genome have revealed that adaptive changes are mediated by complex
      regulatory networks and signals, resulting in temporal gene expression coupled to
      metabolic and energetic changes. An important goal for bacterial physiologists
      will be to elucidate the physiology of M. tuberculosis during the transition
      between the diverse conditions encountered by M. tuberculosis. This review covers
      the growth of the mycobacterial cell and how environmental stimuli are sensed by
      this bacterium. Adaptation to different environments is described from the
      viewpoint of nutrient acquisition, energy generation, and regulation. To gain
      quantitative understanding of mycobacterial physiology will require a systems
      biology approach and recent efforts in this area are discussed.

PMID- 19573706
TI  - Surgical education for gynecologic oncologists.

PMID- 19573707
TI  - Surgical education and training program development for gynecologic oncology:
      American perspective.
AB  - The purpose of this paper is to provide information about gynecologic oncology
      fellowship training and guidance in program development. The characteristics
      necessary for a physician to develop into a successful gynecologic oncologist
      include an extensive fund of knowledge related to the subspecialty, strong
      interpersonal skills, the ability to practice within the complex systems required
      for management of gynecologic cancer patients, surgical expertise, and the
      clinical ability to provide comprehensive oncologic care for these women. In
      order for a trainee to acquire these skills, a gynecologic oncology training
      program must accept only highly qualified individuals as fellows, have a
      dedicated core faculty, practice in a supportive environment that has appropriate
      facilities, and provide adequate clinical material. The gynecologic oncology
      training program must be organized with an emphasis on education of the fellows.
      Part of the educational program is formal (lectures, assigned reading, basic
      skill sets, etc.). Training in clinical and surgical skills is a day-to-day
      process that occurs during the course of patient care. One requirement of The
      American Board of Obstetrics and Gynecology (ABOG) is that the fellow spends 12
      months of protected time doing research. Fellows are also required to take 2
      courses, one in biostatistics and one in cancer biology. A thesis of publishable
      quality is also required. All programs must perform ongoing quality assurance and
      reassessment of potential areas for improvement. ABOG is responsible for the
      accreditation and ongoing monitoring of the fellowship programs.

PMID- 19573708
TI  - Surgical education and training in gynecologic oncology I: European perspective.
AB  - Post-graduate training in oncogynecological surgery should be based on a
      comprehensive system with three main components: training centers, trainers and
      trainees. For each of these components, clearly defined requirements should be
      established. An international consensus on classification, terminology, and
      performance of standard procedures in gynecological oncology would further
      improve postgraduate training. One of the key features of this system should be
      continuous assessment of surgical and non-surgical skills that would make
      possible the evaluation of individual trainees' progress, as well as the quality
      of training centers and trainers. Special attention should be paid to the
      development of tailored educational tools. Internet databases of video
      presentations should be available to trainees, demonstrating standard procedures
      as well as atypical situations, including the management of complications. In
      Europe, the already available programs for postgraduate training and
      accreditation of centers developed by the European Society of Gynecological
      Oncology (ESGO) should become the basis for harmonization of postgraduate
      training in gynecological oncology.

PMID- 19573710
TI  - Advances in coronary angiography. Preface.

PMID- 19573711
TI  - Coronary angiography: the need for improvement and the barriers to adoption of
      new technology.
AB  - Traditional coronary angiography presents a variety of limitations related to
      image acquisition, content, interpretation, and patient safety. These limitations
      were first apparent with coronary angiography used as a diagnostic tool and have
      been further magnified in today's world of percutaneous coronary intervention
      (PCI), with the frequent use of implantable coronary stents. Improvements are
      needed to overcome the limitations in using current two-dimensional radiographic
      imaging for optimizing patient selection, quantifying vessel features, guiding
      PCI, and assessing PCI results. Barriers to such improvements include the paucity
      of clinical outcomes studies related to new imaging technology, the resistance to
      changing long-standing practices, the need for physician and staff member
      training, and the costs associated with acquiring and effectively using these
      advances in coronary angiography.

PMID- 19573712
TI  - Flat detectors and new aspects of radiation safety.
AB  - Flat detectors are the heart of high-performance imaging systems that provide new
      capabilities as well as new hazards. The superior image quality enables operators
      to work with heavier patients and steeper projections. Under these conditions,
      exposure control computers automatically increase the production of x-rays to
      compensate for absorption by body tissues. Image quality is preserved, and
      operators may not be aware of the very high skin doses delivered during prolonged
      procedures. Although it is assumed that flat detector systems are safe, the
      potential for radiation overexposure and skin injury is real. This article
      examines the unique radiation hazards of flat detector fluoroscopy and suggests
      practical steps that clinicians can take to protect themselves and their patients
      from radiation injury.

PMID- 19573713
TI  - Rotational coronary angiography.
AB  - The numerous well-documented limitations of standard fixed-acquisition coronary
      angiography led to the development of rotational angiography. This acquisition
      method uses automated gantry movements while numerous angiographic projections
      are obtained, and thus overcomes many of the limitations of standard angiography.
      This article highlights the techniques, advantages, and disadvantages of each
      type of rotational angiography currently commercially available. Also included is
      a discussion of the evolution of rotational angiography, from its initial
      conception and pilot studies to its latest step forward on the developmental road
      towards enhanced coronary imaging.

PMID- 19573714
TI  - Advances in contrast media and contrast injectors.
AB  - This article reviews the currently available contrast media used for imaging
      during coronary angiography and percutaneous intervention. Recent data regarding
      potential adverse effects of contrast media and strategies to minimize adverse
      events are discussed. In addition, the authors review the state of the art in
      automated contrast injection for coronary angiography, including protocols used
      for performance of rotational coronary angiography and digital subtraction
      imaging in the catheterization laboratory.

PMID- 19573715
TI  - Technique and catheters.
AB  - This article reviews the current technique of coronary angiography, focusing on
      the choice of arterial access site; navigation from the arterial access site to
      the ascending thoracic aorta; cannulation of the native coronary arteries in
      their normal, variant, and anomalous locations; and cannulation of saphenous vein
      and arterial graft conduits. The authors conclude that, although no didactic
      training can substitute for the hands-on apprenticeship obtained during general
      cardiology and interventional cardiology fellowships, the intellectual elements
      fundamental to coronary angiography outlined here will result in a more
      efficient, effective, and safe procedure for patients.

PMID- 19573716
TI  - Three-dimensional coronary visualization, Part 1: modeling.
AB  - Three-dimensional (3D) modeling techniques have been developed for clinical use
      to minimize the imaging limitations of two-dimensional (2D) angiography. The 3D
      models of the coronary arterial tree not only accurately display the complexities
      of coronary anatomy but also enable quantification of vessel curvature,
      measurement of vessel segment length, and identification of the amount of
      radiographic foreshortening and vessel overlap in any simulated angiographic
      projection. This article describes the process and applications associated with
      producing a 3D model of the coronary arterial tree using only a few standard 2D
      projection images from a routine coronary angiographic study.

PMID- 19573717
TI  - Three-dimensional coronary visualization, Part 2: 3D reconstruction.
AB  - Fully automatic generation of a volumetric representation of the coronary artery
      tree can be achieved by rotational coronary angiography acquisition and three
      dimensional tomographic reconstruction. The generated volume datasets can assist
      the physician during percutaneous coronary interventions by visualizing three
      dimensional coronary morphology and offering utility tools to derive various
      quantitative measurements. These utility tools allow lesion assessment, optimal
      working-view selection for specific vessel segments, and improved guidance via
      overlay functionality or follow C-arc. This article gives an overview of
      reconstruction methods, clinical tools, and present clinical data.

PMID- 19573718
TI  - Enhanced x-ray visualization of coronary stents: clinical aspects.
AB  - Coronary stent under expansion is a major contributor to in-stent restenosis and
      acute stent thrombosis. StentBoost and IC Stent are advanced x-ray image
      enhancing techniques that provide improved stent visualization by eliminating
      motion artifact. These techniques can be useful in the detection of inadequate
      stent expansion. These motion-corrected x-ray stent (MXS) visualization
      techniques are more time-efficient compared to intravascular ultrasound (IVUS),
      require less training of catheterization laboratory personnel, and have lower
      procedural costs. However, little clinical or outcome data evidence exist for
      MXS. Though IVUS remains the gold standard for evaluation of the adequacy of
      stent expansion, MXS may be a viable adjunctive imaging tool in certain clinical
      scenarios.

PMID- 19573719
TI  - Advanced visibility enhancement for stents and other devices: image processing
      aspects.
AB  - In non-contrast-enhanced x-ray sequences, the image quality of stents can be
      enhanced by motion compensating and integrating images of exposure sequences.
      Three-dimensional stent reconstruction has been developed to allow enhanced stent
      visualization and assessment in three dimensions. This article gives an overview
      of the different methods used for enhanced stent visualization, describes studies
      that have evaluated these methods, and summarizes results of these methods on
      other cardiac and non-cardiac devices.

PMID- 19573720
TI  - Two and three-dimensional quantitative coronary angiography.
AB  - Following the development of the first automated methods in the 1980s,
      quantitative coronary angiography (QCA) has undergone substantial evolution from
      simplistic computer-assisted methods of visual interpretation of coronary
      angiograms to recently introduced three-dimensional reconstruction and
      quantitative analysis algorithms. The ability of QCA to provide objective
      dimensional assessment of coronary lesions is still useful and has led to its
      widespread application in both scientific research and clinical practice. Most of
      the systems available nowadays are based on vessel edge detection algorithms to
      designate the arterial lumen on conventional two-dimensional coronary angiograms.
      Three generations of these systems have been developed with improved accuracy and
      precision of obtained measurements. Techniques for reconstruction of the two
      dimensional coronary angiogram in space have allowed the implementation of three
      dimensional QCA. This new technology may solve many of the limitations inherent
      in two-dimensional QCA and provide stenosis assessment capabilities not available
      with two-dimensional imaging.

PMID- 19573721
TI  - Computer assistance for solving imaging problems.
AB  - Medical imaging has moved into an era of digital files and processing of images
      to yield three-dimensional models and reconstructions. This development has
      opened up opportunities to apply computer techniques in traditional imaging
      tasks. Two of the most common imaging tasks are those to correct the two
      dimensional projection problems of foreshortening of lesions and of vessel
      overlap. This article explores the use of computers to assist in these tasks, to
      create databases for guiding decision making, to provide graphics to assist the
      physician, and to simulate cardiovascular procedures.

PMID- 19573722
TI  - Coronary computed tomographic angiography in the cardiac catheterization
      laboratory: current applications and future developments.
AB  - The last few years have seen a marked increase in the number of cardiac CT scans
      performed, regardless of reimbursement issues and concerns about radiation dose.
      New-generation multidetector CT (MDCT) scanners with wide craniocaudal coverage
      (256 slices and beyond) have the potential to further improve diagnostic
      capability compared with that of the existing generation of MDCT scanners. New
      dose-reduction technologies are now available on these scanners, enabling high
      quality coronary imaging with a significant reduction in radiation dose. This
      article addresses some of these advances and discusses how cardiac CT and its
      derived information can be used in the preparation and execution of catheter
      coronary angiography and percutaneous coronary interventions.

PMID- 19573723
TI  - Intravascular ultrasound registration/integration with coronary angiography.
AB  - To exploit fully the imaging data derived from both angiography and intravascular
      ultrasound (IVUS), combined visualization is needed. Although this visualization
      has been available in the research environment for the last decade or so,
      clinical implementation is still pending. Recent improvements in computer
      hardware and software (algorithms), improved angiography and IVUS technologies,
      and a total digital imaging workflow could bring integrated IVUS/angiography
      imaging into the catheter laboratory in the near future.

PMID- 19573724
TI  - The future cardiac catheterization laboratory.
AB  - This article describes the major components in the future cardiac catheterization
      laboratory to facilitate cardiac interventions for both coronary artery and
      structural heart diseases.

PMID- 19573725
TI  - Combining antiplatelet and anticoagulant therapies.
AB  - Antiplatelet therapy is the cornerstone for both primary and secondary prevention
      therapies for ischemic events resulting from coronary atherosclerotic disease.
      Dual antiplatelet therapy (aspirin plus a thienopyridine, usually clopidogrel)
      has assumed a central role in the treatment of acute coronary syndromes and after
      coronary stent deployment. In addition to antiplatelet therapy, anticoagulant
      therapy might be indicated for stroke prevention in a variety of conditions that
      include atrial fibrillation, profound left ventricular dysfunction, and after
      mechanical prosthetic heart valve replacement. For this reason, the use of triple
      antithrombotic therapy (a dual antiplatelet regimen plus warfarin) is expected to
      become more prominent, given an aging patient population. But although triple
      therapy can prevent both thromboembolism and stent thrombosis, it is also
      associated with significant bleeding hazards. Furthermore, when bleeding events
      do occur, the challenge of balancing the risk of stent thrombosis or stroke and
      the need for hemostasis requires considerable expertise. It is both prudent and
      timely to review treatment strategies that employ combinations of antiplatelet
      and anticoagulant therapies as well as strategies aimed at reducing bleeding risk
      in patients treated with these therapies.

PMID- 19573726
TI  - Serial intravascular ultrasound analysis of the main and side branches in
      bifurcation lesions treated with the T-stenting technique.
AB  - OBJECTIVES: This study sought to investigate the mechanism of restenosis and the
      predictive value of post-procedural minimum stent area (MSA) in the side branch
      (SB) after coronary bifurcation stenting. BACKGROUND: The mechanism of
      restenosis, especially at the SB ostium, has not been fully elucidated. METHODS:
      This study examined 73 bifurcation lesions with post-procedural and 9-month
      follow-up intravascular ultrasound images for both main vessel (MV) and SB. All
      lesions were treated with drug-eluting stents using the T-stenting technique.
      Analysis included 5 distinct locations: MV proximal stent, MV middle area, MV
      distal stent, SB ostium (<5 mm distal to the neocarina), and SB distal stent.
      RESULTS: Stent expansion was significantly less in the SB than in the MV (87.1 +/
      20.4% vs. 97.0 +/- 29.1%, p = 0.007). The SB ostium was the most frequent site
      of post-procedural MSA. At the SB ostium, follow-up minimum lumen area (MLA)
      correlated with post-procedural MSA (r = 0.81, p < 0.001). The percentage of
      neointimal area was higher at the SB ostium than at the MV proximal, MV distal,
      and SB distal stent (23.8 +/- 18.9% vs. 13.3 +/- 17.3%, 15.4 +/- 20.5%, and 12.5
      +/- 17.2%, p < 0.001). The optimal threshold of post-procedural MSA to predict
      follow-up MLA > or =4 mm(2) at the SB ostium was 4.83 mm(2), yielding an area
      under the curve of 0.88 (95% confidence interval: 0.80 to 0.95). CONCLUSIONS: Our
      data suggest that inadequate post-procedural MSA with increased neointimal
      hyperplasia may cause the SB ostium to be the most frequent site of restenosis
      after percutaneous coronary intervention on bifurcation lesions.

PMID- 19573727
TI  - Longer-term follow-up of patients recruited to the REACT (Rescue Angioplasty
      Versus Conservative Treatment or Repeat Thrombolysis) trial.
AB  - OBJECTIVES: To evaluate the longer-term outcomes for rescue percutaneous coronary
      intervention (R-PCI). BACKGROUND: Thrombolysis remains an important, commonly
      used reperfusion therapy, yet failure to achieve complete reperfusion occurs
      relatively frequently. A number of recent trials have focused on the management
      of patients with thrombolytic failure, including the REACT (Rescue Angioplasty
      Versus Conservative Treatment or Repeat Thrombolysis) trial, which demonstrated a
      significant 6-month benefit favoring R-PCI. However, longer-term maintenance of
      benefit for R-PCI has not been demonstrated. METHODS: Rates of the primary
      composite end point (major adverse cardiac and cerebrovascular events) to 1 year
      and mortality to a median of 4.4 years in 427 patients included in the 3
      randomized arms of the REACT trial (repeat lysis, conservative therapy, and R
      PCI) were analyzed. RESULTS: One-year event-free survival for patients randomized
      to R-PCI was 81.5%, compared with 64.1% for repeat thrombolysis and 67.5% for
      conservative therapy (overall p = 0.004). Adjusted hazard ratio was 0.44 (95%
      confidence interval [CI]: 0.28 to 0.71; p = 0.0008) for R-PCI versus repeat
      thrombolysis and 0.51 (95% CI: 0.32 to 0.83; p = 0.007) for R-PCI versus
      conservative therapy. Adjusted hazard ratio for longer-term (median 4.4 years)
      overall mortality for R-PCI versus repeat thrombolysis was 0.41 (95% CI: 0.22 to
      0.75; p = 0.004) and 0.43 (95% CI: 0.23 to 0.79; p = 0.006) for R-PCI versus
      conservative therapy. There was no difference in either analysis between repeat
      thrombolysis and conservative strategies. CONCLUSIONS: Rescue PCI, previously
      shown to be superior in the short term to both repeat thrombolysis and
      conservative therapy, maintains benefit in terms of long-term mortality. This
      strategy for failed lysis should be mandated as part of thrombolytic-based ST
      segment elevation myocardial infarction protocols.

PMID- 19573728
TI  - The only better alternative to rescue percutaneous coronary intervention is
      primary percutaneous coronary intervention.

PMID- 19573729
TI  - Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial
      salvage in patients with primary acute myocardial infarction.
AB  - OBJECTIVES: We examined whether distinct monocyte subsets contribute in specific
      ways to myocardial salvage in patients with acute myocardial infarction (AMI).
      BACKGROUND: Recent studies have shown that monocytes in human peripheral blood
      are heterogeneous. METHODS: We studied 36 patients with primary AMI. Peripheral
      blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two
      monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow
      cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by
      cardiovascular magnetic resonance imaging as the difference between myocardium at
      risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed
      gadolinium enhancement). Cardiovascular magnetic resonance imaging was also
      performed 6 months after AMI. RESULTS: Circulating CD14(+)CD16(-) and
      CD14(+)CD16(+) monocytes increased in AMI patients, peaking on days 3 and 5 after
      onset, respectively. Importantly, the peak levels of CD14(+)CD16(-) monocytes,
      but not those of CD14(+)CD16(+) monocytes, were significantly negatively
      associated with the extent of myocardial salvage. We also found that the peak
      levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes,
      were negatively correlated with recovery of left ventricular ejection fraction 6
      months after infarction. CONCLUSIONS: The peak levels of CD14(+)CD16(-) monocytes
      affect both the extent of myocardial salvage and the recovery of left ventricular
      function after AMI, indicating that the manipulation of monocyte heterogeneity
      could be a novel therapeutic target for salvaging ischemic damage.

PMID- 19573730
TI  - Monocyte diversity in myocardial infarction.

PMID- 19573731
TI  - Giant T-U waves precede torsades de pointes in long QT syndrome: a systematic
      electrocardiographic analysis in patients with acquired and congenital QT
      prolongation.
AB  - OBJECTIVES: This study sought to identify electrocardiographic (ECG) criteria
      that are associated with initiation of torsades de pointes (TdP) in patients with
      acquired (a-) and congenital (c-) long QT syndrome (LQTS). BACKGROUND:
      Electrocardiographic criteria used as risk predictors for TdP commonly rely on a
      prolonged QT interval but rarely consider abnormal T-U waves. METHODS: We
      analyzed ECG recordings with TdP from 35 LQTS patients (15 c-LQTS and 20 a-LQTS)
      and compared them with premature ventricular complexes (PVCs) from 40 patients
      with normal QT intervals and with PVCs in 24 of the 35 LQTS patients not related
      to TdP. RESULTS: Abnormal T-U waves (6.2 +/- 0.9 mm) directly preceded TdP in 34
      of 35 LQTS patients and were larger than T-wave amplitude (2.8 +/- 0.2 mm) in
      control patients and larger than the largest T-U-wave in LQTS without TdP (4.7 +/
      0.8 mm). The TdP-initiating beat emerged from a T-U-wave in 27 of 35 LQTS
      patients and in none of 40 control patients. The QRS duration of the first TdP
      beat (175 +/- 12 ms) was longer than in control PVCs (145 +/- 4 ms) and in PVCs
      in LQTS patients not related to TdP (138 +/- 22 ms). The QRS angle was less steep
      before TdP than in other PVCs (all p < 0.05). CONCLUSIONS: Abnormal, giant T-U
      waves separate TdP initiation in LQTS patients from PVCs in other heart disease
      and from other PVCs in LQTS patients. These ECG analyses suggest that early
      afterdepolarizations initiate TdP and, if present, may help to identify an
      imminent risk for TdP.

PMID- 19573732
TI  - Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission
      tomography added value of coronary flow reserve.
AB  - OBJECTIVES: The goal of this study was to assess the predictive value of
      myocardial perfusion imaging with (13)N-ammonia positron emission tomography
      (PET) and coronary flow reserve (CFR) on long-term prognosis in patients with
      suspected myocardial ischemia. BACKGROUND: No prognostic data exist on the
      predictive value of CFR and (13)N-ammonia PET. METHODS: Perfusion and CFR were
      assessed in 256 patients using (13)N-ammonia PET, and follow-up was obtained in
      245 (96%) patients. Sixteen early revascularized patients were excluded and 229
      were assigned to normal versus abnormal perfusion or normal versus abnormal CFR
      (<2.0). Major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial
      infarction, late revascularization, or hospitalization for cardiac reasons) were
      assessed using the Kaplan-Meier method. Cox proportional hazard regression was
      used to identify independent predictors for cardiac events. RESULTS: During
      follow-up (5.4 +/- 2.2 years), 78 patients had at least 1 cardiac event,
      including 29 cardiac deaths. Abnormal perfusion (n = 126) was associated with a
      higher incidence of MACE (p < 0.001) and cardiac death (p < 0.05). In patients
      with normal perfusion, abnormal CFR was independently associated with a higher
      annual event rate over 3 years compared with normal CFR for MACE (1.4% vs. 6.3%;
      p < 0.05) and cardiac death (0.5% vs. 3.1%; p < 0.05). In abnormal perfusion, CFR
      remained predictive throughout the 10-year follow-up (p < 0.001). CONCLUSIONS:
      Perfusion findings in (13)N-ammonia PET and CFR are strong outcome predictors.
      CFR allows further risk stratification, suggesting a "warranty" period of 3 years
      if normal CFR is associated with normal perfusion. Conversely, in patients with
      abnormal perfusion, an impaired CFR has added value for predicting adverse
      outcomes.

PMID- 19573733
TI  - Quantification of myocardial flow reserve using positron emission imaging the
      journey to clinical use.

PMID- 19573734
TI  - The effect of age, diagnosis, and previous surgery in children and adults
      undergoing heart transplantation for congenital heart disease.
AB  - OBJECTIVES: We sought to evaluate the outcomes and identify risk factors for
      mortality after heart transplantation (HT) for congenital heart disease (CHD) in
      infants, children, and adults. BACKGROUND: CHD is considered a risk factor for
      mortality after HT, yet this unique group of patients represents a spectrum of
      complexity. METHODS: There were 488 patients transplanted for CHD from the
      combined Pediatric Heart Transplant Study (1993 to 2002, n = 367) and the Cardiac
      Transplant Registry Database (1990 to 2002, n = 121) who were analyzed. RESULTS:
      The median age at HT was 12.4 years. Primary diagnosis included single ventricle
      (36%), d-transposition of the great arteries (12%), right ventricular outflow
      tract lesions (10%), l-transposition of the great arteries (8%),
      ventricular/atrial septal defects (8%), left ventricular outflow obstruction
      (8%), and other (18%). Ninety-three percent of patients had at least 1 operation
      before HT. Survival at 3 months post-HT was significantly worse in CHD patients
      versus children with cardiomyopathy, but not adults with cardiomyopathy (86%,
      94%, and 91%, respectively). There was no difference in conditional 3-month
      survival among the 3 groups. Five-year survival was 80%. Risk factors for early
      mortality were older recipient age, older donors with longer ischemic times, and
      pre-HT Fontan operations. Predicted survival in Fontan patients was lower (77%
      and 70% at 1 and 5 years) versus non-Fontan patients (88% and 81% at 1 and 5
      years). Risk factors for constant phase mortality included younger recipient age,
      higher transpulmonary gradient, cytomegalovirus mismatch at HT, and earlier
      classical Glenn operation. CONCLUSIONS: Patients undergoing transplantation for
      CHD have a good late survival if they survive the early post-operative period.
      Risk factors for reduced survival are older age at transplant and a previous
      Fontan operation.

PMID- 19573735
TI  - Fundamental differences in electrophysiologic and electroanatomic substrate
      between ischemic cardiomyopathy patients with and without clinical ventricular
      tachycardia.
AB  - OBJECTIVES: The aim of this study was to compare the electrophysiologic substrate
      in ischemic cardiomyopathy (ICM) patients with and without sustained monomorphic
      ventricular tachycardia (SMVT). BACKGROUND: Despite the universal presence of
      potentially arrhythmogenic left ventricular (LV) scarring, it is not clear why
      the majority of ICM patients never develop SMVT. METHODS: Detailed
      electroanatomic mapping of the LV endocardium was performed in 17 stable control
      ICM patients (16 males) without clinical SMVT. They were compared with 17 ICM
      patients (15 males) with spontaneous SMVT. Standard definitions of low-voltage
      zones and fractionated, isolated, and very late potentials were used. RESULTS:
      There were no significant baseline differences between the groups in terms of LV
      diameter, ejection fraction (27% vs. 28%), infarct territory, or time from
      infarction. However, control patients had smaller total low-voltage area < or
      =1.5 mv (30% of surface area vs. 55%, p < 0.001); smaller very low-voltage area
      <0.5 mv (7.3% vs. 29%, p < 0.001); higher mean voltage of low-voltage zones;
      fewer fractionated, isolated, and very late potentials with lower density of
      these scar-related electrograms per unit low-voltage area; and less SMVT
      inducibility. Potential conducting channels within dense scar and adjacent to the
      mitral annulus were more frequent in SMVT patients. CONCLUSIONS: Compared with
      ICM patients with SMVT, an otherwise similar control group demonstrated markedly
      smaller endocardial low-voltage zones, lower scar-related electrogram density,
      and fewer conducting channels with faster conduction velocity. These findings may
      explain why some ICM patients develop SMVT and others do not.

PMID- 19573736
TI  - Why are (only) some infarcted hearts arrhythmogenic?

PMID- 19573737
TI  - Anomalous origin of left coronary artery from innominate artery.

PMID- 19573738
TI  - President's Page: Relations with industry: thoughts on claims of a broken system.

PMID- 19573740
TI  - Serendipity.

PMID- 19573739
TI  - Chronobiological patterns of onset of Tako-Tsubo cardiomyopathy: a multicenter
      Italian study.

PMID- 19573741
TI  - Rasch analysis informed the development of a classification system for a diabetes
      specific preference-based measure of health.
AB  - OBJECTIVE: To develop a classification system (CS) for a diabetes-specific
      preference-based measure of health titled the Diabetes Utility Index (DUI). STUDY
      DESIGN AND SETTING: Factor analysis of the Audit of Diabetes-Dependent Quality-of
      Life (ADDQoL) items (n=385) identified plausible attributes. An expert panel
      provided qualitative input, including additional items. Data from three pilot
      rounds on patients with type 1 or type 2 diabetes were analyzed using Rasch
      analysis (RA). In a validation survey, the final version of the CS was mailed
      along with the SF-12v2, Well-Being Questionnaire, and Diabetes Empowerment Scale
      Short Form to a convenience sample (type 1 or type 2 diabetes). RESULTS: Factor
      analysis identified two plausible attributes. Experts rated the importance of
      ADDQoL and additional items, described attributes from item sets and suggested
      severity levels. Three pilot rounds (n1=52, n2=65, n3=111) tested versions of a
      CS, containing five attributes with severity levels that were modified using RA
      and expert input. The final attributes were Physical Ability and Energy,
      Relationships, Mood and Feelings, Enjoyment of Diet, and Satisfaction with
      Management of Diabetes. The validation survey (n=396) results indicated
      satisfactory Rasch fit statistics, reliability, and severity scaling, whereas
      correspondence of responses to the CS with included measures suggested validity.
      CONCLUSION: Results provide initial report of the validity and reliability of the
      CS of the DUI.

PMID- 19573742
TI  - Dealing with long-term problems after endovascular and open aortic repair.
      Introduction.

PMID- 19573743
TI  - Thoracic aortic dissection: long-term results of endovascular and open repair.
AB  - Treatment paradigms for aortic dissection are based upon the types of
      complications with which the patients present. For acute uncomplicated
      dissection, medical therapy is preferred. Endovascular repair is preferred for
      patients with acute distal dissection complicated by end-organ malperfusion,
      rupture, or aneurysmal degeneration. For patients with chronic dissection with
      aneurysm, open repair is preferred if safe, and endovascular treatment should be
      limited to highest-risk patients because of the uncertainty of success with this
      approach. For intermediate-risk patients, hybrid repairs provide a good
      alternative. Ultimately, improvement in long-term outcomes after treatment of
      aortic dissection still depends on prevention of end-organ ischemia and
      aneurysmal degeneration of the chronically dissected distal aorta. Although the
      evidence base for the roles of various approaches is lacking, data currently
      being accrued and must be closely analyzed to better estimate both the short- and
      long-term benefits of these complementary treatment strategies.

PMID- 19573744
TI  - Follow-up paradigms for stable aortic dissection.
AB  - While limited data exist on which follow-up paradigms for chronic aortic
      dissections can be based, what information is present suggests that long-term
      follow-up is mandatory. In spite of the treatment modality, deaths from aortic
      disease continue to accrue and repeat interventions are often required over long
      term follow-up. The only prospective trial data available indicate a roughly
      equal incidence of secondary interventions during the first and second year.
      Recent studies with longer follow-up suggest that the likelihood of a need for
      intervention ultimately diminishes. With increasing time after presentation, it
      may be possible to decrease the frequency of follow-up interrogations. Definitive
      recommendations in this regard, however, must await the availability of longer
      term data.

PMID- 19573745
TI  - Long-term durability of open thoracic and thoracoabdominal aneurysm repair.
AB  - Results of open surgical repair of descending and thoracoabdominal aortic
      aneurysms have improved dramatically over the years. Nevertheless, while
      adjunctive protective strategies, such as spinal cord drainage and distal aortic
      perfusion, have improved outcomes, clinical challenges remain. In the current
      era, thoracic aortic surgeons must possess both open and endovascular stent-graft
      capabilities to offer these complex patients the most optimal and individualized
      treatment approach. Herein we summarize the contemporary outcomes of open
      surgical repair of patients with either descending thoracic or thoracoabdominal
      aortic aneurysms, focusing on the risk of complications and means for preventing
      their occurrence.

PMID- 19573746
TI  - Late failure after endovascular repair of descending thoracic aneurysms.
AB  - Although endovascular repair of descending thoracic aneurysm has been
      increasingly utilized as a minimally invasive alternative to open repair, the
      availability of late results remains quite limited, and what exists does not yet
      completely reflect the rapid evolution of devices, refinement in delivery systems
      and maturation of both institutional and general learning curves. Durability of
      endografts in the thoracic aorta continues to be defined as more long-term data
      emerge from the major device regulatory trials. This review describes the
      currently available published long-term results and describes some of the
      anecdotally reported modes of late failure associated with the technique.

PMID- 19573747
TI  - Late complications after endovascular thoracoabdominal aneurysm repair.
AB  - Thoracoabdominal aortic aneurysm repair has evolved substantially during the past
      several decades since its first description over 50 years ago. Despite
      technological improvements, however, patients continue to face significant risks
      of perioperative mortality, spinal cord ischemia, and worsening renal function.
      Endovascular repair of thoracoabdominal aortic aneurysms is still in its infancy,
      but there now exists a growing body of experience with fenestrated and branched
      endografts. Long-term follow-up is scant, but endovascular repair does appear to
      provide some protection against development of spinal cord ischemia. In addition,
      the less invasive techniques may provide safer alternatives to conventional
      surgery in treating these high-risk patients. Outcomes will certainly continue to
      improve with our growing experience and with the refinement of this technology.

PMID- 19573748
TI  - Fate of proximal aorta following open infrarenal aneurysm repair.
AB  - Open repair of abdominal aortic aneurysm (AAA) is considered a stable and durable
      vascular procedure when compared with the more recent endovascular approach. A
      process of remodeling and progressive degeneration may occur after open surgery
      in the aorta proximal to the repair, predisposing to proximal recurrent aneurysm
      formation. Surgical repair of the false aneurysm carries a high rate of
      perioperative complications, including spinal cord ischemia and renal
      insufficiency. The literature is conflicting on the frequency of proximal false
      aneurysm formation, but an average neck dilation of between .2 and .6 mm per year
      has been reported. Importantly, disease progression may be the most common
      underlying culprit for proximal false-aneurysm formation. These findings argue
      for careful follow-up after aneurysm repair using high-quality imaging studies to
      detect failures and the potential for false-aneurysm formation.

PMID- 19573749
TI  - Fate of iliac arteries following open abdominal aortic aneurysm repair.
AB  - Iliac artery aneurysms are a frequent finding in patients with abdominal aortic
      aneurysms. The decision of whether to perform a tubular or bifurcated repair
      rests on a balance between the natural history of the iliac arteries during the
      lifetime of the patient versus the risk of symptomatic pelvic ischemia and the
      increased complexity of a bifurcated repair. The relatively recent increase in
      the use of cross-sectional imaging, especially in the setting of long-term
      endograft surveillance, has provided useful data on which to base these clinical
      decisions. A tube graft repair appears to be safe and durable in patients
      undergoing open aneurysm repair, when suitable distal aortic anatomy and normal
      iliac arteries are present. A bifurcated graft should be considered in younger
      patients with moderate sized iliac aneurysms (<30 mm in diameter), as well as in
      almost all patients with larger iliac aneurysms.

PMID- 19573750
TI  - Durability of endovascular infrarenal aneurysm repair: when does late failure
      occur and why?
AB  - The first commercially available stent grafts were unable to withstand the
      hemodynamic forces of the vascular environment. The past 15 years have seen a
      gradual improvement in long-term stent graft performance as designs evolved
      through the elimination of features associated with late failure and the
      replication of features associated with durable success. Clinical experience
      provides the following principles on which to base device design and implantation
      techniques. Few patients have an adequate length of non-dilated aorta distal to
      the aneurysm to allow implantation of an aorto-aortic stent graft; bifurcated
      stent grafts are usually required for AAA repair. Friction, column strength and
      tissue ingrowth do not prevent migration of the stent graft from its attachment
      within the neck into the aneurysm; some form of active fixation is required,
      usually in the form of barbs. Any movement between the apex of a stent and the
      overlying graft material will erode the fabric; stents and grafts need to move as
      a single unit. Nitinol is versatile, but fragile; Nitinol components must be
      polished to eliminate all surface irregularities and they cannot be subjected to
      compression loading, or excessive pulsatile movement. The neck of an aneurysm is
      unstable; it will dilate unless protected by a securely fixed, non-compliant
      stent graft. The aneurysm does not heal; freedom from risk of rupture depends on
      durable depressurization of the sac. The sole objective of image-based follow-up
      is the early detection, and catheter-based correction, of device failure. Once
      any given design has been in use long enough to identify its failure modes, the
      frequency of follow-up studies can be adjusted accordingly. However, it takes a
      long time to identify all the potential forms of late failure, and pre-clinical
      testing remains an imprecise science. New, or recently modified, devices cannot
      necessarily be assumed to be as durable as their predecessors.

PMID- 19573751
TI  - Future technologies to address the failed endoprosthesis.
AB  - Endovascular aneurysm repair (EVAR) has transformed therapy for aortic aneurysms
      and introduced an era of widespread use for endovascular procedures in a variety
      of vascular beds. While dramatic improvements in acute outcomes drove the early
      enthusiasm for EVAR, a realization that the integrity of the endoprostheses used
      for EVAR was significantly inferior to results obtained with open surgical
      reconstruction dampened enthusiasm for their use in low-risk patients and
      mandated long-term follow-up for EVAR patients. The future of EVAR as a primary
      approach to aortic aneurysm repair rests on development of technologies and
      techniques that can reproduce the foundations and, therefore, the results of open
      surgical reconstruction. Many of these technologies will be used initially to
      address the failing endoprostheses, but will have a larger role in their
      application as a primary component of EVAR.

PMID- 19573753
TI  - Preface: Chronic diseases in childhood obesity: risks and benefits of early
      intervention. Ohio, April 2-3, 2009.

PMID- 19573752
TI  - Dilatation of aortic grafts over time: what to expect and when to be concerned.
AB  - Dilatation of aortic prosthetic grafts is commonly reported, but most reports are
      anecdotal, with little objective data in the literature. We performed a
      prospective trial of 303 patients who underwent prosthetic graft repair for
      aortic aneurysm or occlusive disease, randomizing patients between insertion of a
      woven polyester or expanded polytetrafluoroethylene (ePTFE) graft. Patients were
      followed with computed tomography and ultrasonography for up to 5 years in order
      to assess the frequency and magnitude of postoperative dilatation. Graft
      dilatation was documented in patients with polyester grafts at 12 months.
      Thereafter and up to 60 months, polyester grafts did not dilate further. After 5
      years, polyester prostheses had dilated by 25% and ePTFE by 12.5%, as determined
      by computed tomography imaging. These observations suggest that dilatation of
      prosthetic grafts is more frequent with knitted polyester grafts compared with
      ePTFE. Dilatation occurs within the first year after implantation and can be, in
      part, explained by a discrepancy between the initial nominal graft diameter and
      its diameter after clamp release, probably due to an in vivo adaptation of the
      textile structure. Interestingly, graft dilatation did not appear to be
      associated with an increased frequency of graft-related complications.

PMID- 19573754
TI  - Changes in physiology with increasing fat mass.
AB  - Obesity has reached epidemic proportions in the USA with a nearly fourfold rise
      in the prevalence of childhood obesity. There are many possible etiologies of
      obesity as the adipose tissue plays a significant, complex role in the physiology
      of fuel metabolism and hormone regulation. The development of obesity represents
      a pathophysiologic increase in fat mass in which multiple metabolic pathways are
      deranged. The consequences of these metabolic derangements, including insulin
      resistance and inflammation, are reflected in obesity-related comorbidities and
      can be seen in the setting of pediatric obesity. Obese adolescents demonstrate
      increased rates of early maturation, orthopedic growth abnormalities, diabetes
      mellitus, obstructive sleep apnea, hypertension, steatosis, and polycystic
      ovarian syndrome, placing this group of children at risk for long-term health
      problems and reduced quality of life. Given the negative short- and long-term
      impact of obesity on children, careful attention should be paid to the unique
      health issues of this "at-risk" population with both prevention and early
      intervention strategies.

PMID- 19573755
TI  - Use of the metabolic syndrome in pediatrics: a blessing and a curse.
AB  - The clustering of traditional cardiovascular disease risk factors is known as the
      metabolic syndrome. The metabolic syndrome was first characterized as a distinct
      entity by Dr. Gerald Reaven in 1988. The intent was to identify individuals at
      greatest risk for cardiovascular disease mortality and those in urgent need of
      lifestyle intervention. Since then the metabolic syndrome has evolved into a
      diagnosable entity recognized by the National Cholesterol Education Program,
      Adult Treatment Panel III, World Health Organization, and the International
      Diabetes Foundation. However, the metabolic syndrome as a diagnosis faces
      considerable controversy, particularly when applied to the pediatric population.
      Due to the changes in growth and development, the adult criteria for the
      metabolic syndrome cannot be applied to children and adolescents. In fact,
      currently no all-inclusive definition for the metabolic syndrome exists for
      pediatrics. Despite its controversies, the identification of the metabolic
      syndrome and its component disorders in childhood and adolescence offers
      important information about risk for cardiovascular disease. Emerging evidence
      points to the presence of early functional and morphologic changes to the heart
      and blood vessels among obese children with the metabolic syndrome phenotype.
      Yet, the plasticity of the cardiovascular system during childhood and adolescence
      allows for the reversal of cardiovascular damage, but only if risks are
      identified early and treated aggressively. Recent national recommendations and
      screening directives offer pediatricians a comprehensive guide to risk
      prevention, assessment, and treatment.

PMID- 19573756
TI  - Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the
      implications for bariatric surgery.
AB  - This review focuses on the diagnosis, risk factors, prevalence, pathogenesis and
      treatment of pediatric nonalcoholic steatohepatitis (NASH). NASH is a progressive
      form of nonalcoholic fatty liver disease (NAFLD), the most common cause of
      chronic liver disease in children. The factors that account for differences
      between children with NASH and children with milder forms of NAFLD are unclear.
      The diagnosis of NASH requires interpretation of liver histology because no
      noninvasive markers predict the presence or severity of NASH. There is no proven
      treatment for NASH. Several clinical trials for NAFLD are in progress; however,
      clinical trials focusing on NASH are needed. Heightened physician awareness of
      NAFLD, NASH, and associated risk factors is important to identify and treat
      affected children.

PMID- 19573758
TI  - Weighing risk: the expert committee's recommendations in practice.
AB  - In 2005, an expert committee was convened on behalf of the American Medical
      Association, the Health Resources and Service Administration, and the Centers for
      Disease Control and Prevention to update the previous recommendations on the
      evaluation and treatment of childhood obesity. Fifteen national health care
      organizations, which served children, participated in writing these
      recommendations. This article reviews recommendations on assessment of BMI,
      nutrition and activity, and obesity-related comorbidities. Principles of obesity
      prevention and treatment are discussed and high-risk eating and activity
      behaviors are addressed. Prevention and treatment of obesity are reviewed as set
      in the context of the Medical Home using the principles of the chronic disease
      model. The stepwise approach to obesity treatment and prevention is reviewed
      along with specific evidence-based/informed strategies. The skills needed to
      implement the recommendations, such as integration of the care team, roles and
      training, links to the health care system, connection to the community, and the
      role of the subspecialist, are discussed.

PMID- 19573757
TI  - Diet, exercise, behavior: the promise and limits of lifestyle change.
AB  - The prevalent surge in childhood and adolescent obesity within the past 3 decades
      poses a significant challenge for many pediatric clinicians who are charged with
      treating this condition. Comprehensive, research-based pediatric obesity
      treatment programs are essential to addressing this problem and preventing the
      transition of obesity and its many comorbidities into adulthood. This paper will
      identify dietary, physical activity, and behavioral approaches to lifestyle
      change and describe how they are incorporated as part of multidisciplinary
      treatment interventions in youth. Specific tailoring of treatment programs to
      address age and varying degrees of overweight and obesity will also be presented
      along with recommendations for future research.

PMID- 19573759
TI  - Medical versus surgical interventions for the metabolic complications of obesity
      in children.
AB  - The global epidemic of obesity has not spared children. Although prevention of
      obesity is commendable, we cannot hide from the pressing need to identify,
      assess, and actively manage children seriously afflicted by obesity and its
      associated conditions. Sustained weight loss (or, for children, lowering of body
      mass index standard deviation score) delivers major health benefit, but in
      children has been difficult to achieve. In adults, the success of the diabetes
      prevention programs using practical lifestyle interventions is indisputable.
      Medical therapy, although currently limited in it scope, provides some promise
      for older children. There is now accumulating evidence, generally of poor quality
      that surgical interventions (laparoscopic adjustable gastric banding and Roux-en
      Y gastric bypass) provide excellent sustained weight loss and improvement in
      comorbidity and quality of life in selected older children. Their benefits in
      adults are well demonstrated. Surgery comes with risk, both immediate and in the
      future, as does severe obesity. Carefully weighing risk and benefit is
      challenging for the individual and for health service providers. Careful health
      outcomes research with registries and well-conducted trials will provide better
      direction in the future. In the meantime, we should move forward ethically and
      cautiously in providing more intensive obesity management in children.

PMID- 19573760
TI  - How young for bariatric surgery in children?
AB  - Obesity affects 50% of adults and 18% of children in the USA. It has wide-ranging
      comorbidities with clinical, psychosocial, and economic ramifications. Obesity
      refers to a condition of excess body fat. The basis for weight gain is a
      fundamental imbalance between caloric intake and output, but individual variation
      based on genetics, metabolism, and diverse environmental triggers is seen.
      Although modifications to our obesogenic society and education about the risks in
      our environment may lead to a decrease in the incidence of obesity through
      prevention, treatment for those already obese is critically important. In adults,
      the most successful treatment programs for obesity include a surgical procedure.
      This article discusses the problems obesity presents to children and their
      families, highlights the unique aspects of treating obesity in children, reviews
      the currently utilized bariatric surgical procedures, and introduces those
      bariatric procedures that are under development. When considering whether to use
      bariatric surgical procedures in a multidisciplinary weight management program
      for children, the special needs and characteristics of children with a severe
      weight problem must be considered. Development of bariatric surgical techniques
      and devices and implementation of these tools in multidisciplinary weight
      management programs need greater attention. This will require the combined
      efforts of the pediatric health care providers from many specialties and
      partnerships with industry to facilitate discovery and implementation.

PMID- 19573761
TI  - Ethical issues in pediatric bariatric surgery.
AB  - Performance of bariatric surgery in pediatric patients carries profound ethical
      burdens for all stakeholders: morbidly obese children and adolescents, their
      parents and families, pediatric physicians and surgeons, pediatric health care
      institutions, and society. The decision to proceed with a bariatric intervention
      should be made only after it is established that the patient's comorbidities
      could not be treated with less invasive means, the patient has a favorable
      risk/benefit profile, the patient and her/his family have received extensive
      preoperative counseling and given informed consent, and the pediatric bariatric
      team has a comprehensive system of short- and long-term care. The patient and
      her/his family should be counseled about the innovative aspects of the bariatric
      intervention, in which sustained weight loss and potential complications are
      unknown. The pediatric surgeons and their respective institutions that offer
      bariatric surgery should be enrolled in clinical research endeavors that assess
      outcomes and seek optimal treatment protocols.

PMID- 19573763
TI  - Inferential statistics.

PMID- 19573764
TI  - A pregnant woman with edema: conclusion.

PMID- 19573766
TI  - Knowing our limits.

PMID- 19573767
TI  - The bougie-aided cricothyrotomy.

PMID- 19573768
TI  - The feasibility of daily mannequin practice to improve intubation success.
AB  - INTRODUCTION: Opportunities to practice live intubations are limited, so other
      methods of skill development must be researched. Some experts claim that
      exceptional performance simply reflects extended periods of intense training.
      This study evaluates whether daily intubation practice using standard airway
      mannequins increases the success rate of providers when intubating actual
      patients. METHODS: Study participants were members of a ground critical care
      transport team. Investigators performed a review of previous trips, compiling the
      number of attempts at intubation and success rates. During the intervention
      period, participants were asked to perform repeated daily intubations of airway
      mannequins. Intubation success rates and compliance with study protocols were
      recorded. RESULTS: The rate of successful intubation of the mannequins was
      constant, with a linear regression slope of 0.00016 (95% confidence interval
      [CI]: -0.0039, 0.0042). A generalized estimation equations logistic regression
      comparing success rates between the pre-intervention and the intervention periods
      showed no statistical difference (P=.63, z=0.48), with an odds ratio of 1.37 (95%
      CI: 0.38, 4.92). However, compliance with the study declined significantly over
      the intervention period, as indicated by a linear regression slope of 0.0239 (95%
      CI: -.0354, -0.0124). CONCLUSIONS: Daily practice with standard airway mannequins
      by a critical care transport team did not improve intubation success on actual
      patients.

PMID- 19573769
TI  - Videolaryngoscope-assisted nasotracheal intubation for the difficult airway in
      trauma.

PMID- 19573770
TI  - Outcomes and quality of care in urology.

PMID- 19573771
TI  - Defining high quality health care.
AB  - Most health care quality improvement efforts target measures of health care
      structures, processes, and/or outcomes. Structural measures examine relatively
      fixed aspects of health care delivery such as physical plant and human resources.
      Process measures, the focus of the largest proportion of quality improvement
      efforts, assess specific transactions in clinical-patient encounters, such as use
      of appropriate surgical antibiotic prophylaxis, which are expected to improve
      outcomes. Outcome measures, which comprise quality of life endpoints as well as
      morbidity and mortality, are of greatest interest to clinicians and patients, but
      entail the greatest complexity, as the majority of variance in outcomes is
      attributable to patient and environmental factors that may not be readily
      modifiable. Selecting among structure, process, and outcome measures for quality
      improvement efforts generally will be dictated by the specific clinical situation
      for which improvement is desired. One aspect of health care quality that has
      received a great deal of attention in recent years is the relationship between
      surgical volume and health outcomes. Volume, an inherent characteristic of a
      health care facility or provider, is generally considered a structural measure of
      quality. Many studies have demonstrated a positive association between volume and
      outcomes, and policymakers in the private and public sectors have begun to
      consider volume in certification and reimbursement decisions. The volume-outcome
      association is not without controversy, however. Most studies in the field are
      limited by the nature of the administrative data on which they are based, and
      some studies have found that variation in quality within volume quantiles exceeds
      differences between quantiles. Moreover, regionalization driven by a focus on
      volume may exert adverse effects on access to care. The movement for health care
      quality improvement faces substantial methodological, clinical, financial, and
      political challenges. Despite these challenges, it is a movement that is gaining
      momentum, and the emphasis on quality in health care delivery is likely only to
      increase in the future. It is crucial, therefore, that physicians assume
      increasing leadership roles in efforts to define, measure, report, and improve
      quality of care.

PMID- 19573772
TI  - Do high-volume hospitals and surgeons provide better care in urologic oncology?
AB  - Studies focusing primarily on hospital or surgical volume as a surrogate for
      surgical experience have found substantial variations in outcomes. Increasing
      surgical experience has been shown to improve outcomes after multiple procedures,
      including esophagectomy, pancreatectomy, and primary surgery for colon and breast
      cancer. More recently, evidence has been presented that surgical
      volume/experience affects quality of life and cancer control outcomes after
      urologic oncology procedures. Although most of these data pertain to radical
      prostatectomy, similar conclusions have been reached for radical cystectomy,
      retroperitoneal lymph node dissection, and management of renal cell carcinoma.
      This review highlights data indicating that high-volume surgeons and hospitals
      provide better care for radical prostatectomy.

PMID- 19573773
TI  - The critical limitations of volume-outcome analysis.
AB  - There is a justified assumption that the patient outcome is in large part
      determined by the quality of the care they receive. For certain procedures
      outside of the field of urology, it has been demonstrated that higher surgical
      volume, either at the hospital or surgeon level is a proxy for higher quality of
      care. Multiple studies have followed this line of inquiry and attempted to show
      that volume may also predict outcome for certain urologic procedures. Review of
      the published studies shows that the association appears quite weak. However, the
      real weakness of this line of study is not so much in the findings, but in the
      universally used and critically flawed study methodology. This article
      demonstrates how a simple study design flaw has proved to be the Achilles heal of
      this entire line of research.

PMID- 19573774
TI  - Quality of care indicators for prostate cancer: progress toward consensus.
AB  - Previously-documented variations in patterns of care and patient outcomes suggest
      differences in the quality of care provided to men with prostate cancer. Herein
      we describe ongoing efforts to measure the quality of prostate cancer care,
      including the development and pilot-testing of the RAND prostate cancer quality
      indicators and the selection of the consensus-based Physician Performance
      Measurement Set for Prostate Cancer. We also summarize current payer-led
      initiatives aimed at measuring quality of care for men with prostate cancer. We
      conclude that currently-available prostate cancer quality indicators are derived
      from valid, consensus-based methodologies and capture clinical practices that are
      necessary for high-quality care in early-stage prostate cancer. Despite this
      promise, however, the currently available measures have several limitations that
      should be considered during their implementation in prostate cancer quality
      assessment and improvement activities.

PMID- 19573775
TI  - Candidate quality of care indicators for localized bladder cancer.
AB  - The surgical management of clinically localized bladder cancer is challenging,
      and the quality of care delivered to patients with bladder cancer is a subject of
      increasing interest. Multiple large studies have examined the association between
      surgical volume and outcomes after radical cystectomy. These studies generally
      find lower mortality and complication rates at high-volume centers, though
      interpretation of the data must be tempered by limitations of the datasets
      driving the studies. Benefits of regionalization of care also must be weighed
      against other measures proven to predict outcomes; a delay in time to cystectomy
      beyond 3 months, for example, is strongly associated with increased mortality.
      Other candidate process measures supported by existing literature include
      adequacy of lymphadenectomy as measured by nodal yield and availability or
      offering of orthotopic diversion when appropriate. Assessment and reporting of
      bladder cancer outcomes should be risk adjusted based on oncologic risk factors
      and patient comorbid illness. Perioperative morbidity and mortality, cause
      specific survival, and overall survival are all key measures. Assessment of
      health-related quality of life after bladder cancer treatment should also be
      standardized for reporting. Multiple survey instruments have been developed in
      recent years, but none has yet been well validated or widely adopted. In
      particular, capturing variation in quality of life outcomes between patients
      undergoing bladder-sparing protocols vs. continent diversion vs. incontinent
      diversion is an important but difficult goal that has not yet been met. The
      urologic oncology community should take a strong lead in achieving consensus
      regarding the definition, assessment, and reporting of quality of care data for
      bladder cancer.

PMID- 19573776
TI  - Understanding the relationship between health care quality and the renal mass.
AB  - Quality is increasingly important to all stakeholders of the U.S. health care
      system. Endeavors to measure and improve quality have moved forward in
      cardiovascular disease, diabetes care, and surgical wound infections. However, in
      urology, such efforts have lagged. As a specialty, we are now faced with
      pressures, exerted primarily by payors, to roll out performance measures, or
      quality indicators, in the absence of science to support them. In this review, we
      discuss the broad concepts of health care quality and describe their
      relationships with small renal tumors.

PMID- 19573777
TI  - Quality of care for testis cancer.
AB  - This article explores the delivery of high quality care in patients with
      testicular cancer. Critical issues relate to an individualized, risk-stratified,
      and multidisciplinary approach to patient care at centers of excellence and
      subsequent close patient follow-up. The necessary integration of multiple
      therapeutic modalities makes testis cancer outcomes highly susceptible to
      variations in quality of care, which deserves further investigation in well
      designed population-based studies.

PMID- 19573778
TI  - Response to the article by J.E. Montie, Screen detected, low volume prostate
      cancer: the case for active treatment. Urol Oncol 2008;26:511-515.

PMID- 19573791
TI  - Developments in fluorescent probes for receptor research.
AB  - Early reports on the identification of fluorescent probes for receptors date back
      to mid-1970s. Fluorescent probes were initially used to visualize molecular
      targets in an analogous way to the use of fluorescent antibodies but with the
      same resolution as isotopically labelled ligands. In parallel to the rapid
      development of techniques, such as fluorescence correlation spectroscopy, multi
      photon excitation fluorescence microscopy, fluorescence polarization and in vivo
      fluorescence imaging, fluorescent probes are becoming multifaceted tools in life
      science. The present review will focus on how the design of fluorescent ligands
      for receptors has evolved to meet the needs of most recent fluorescence
      applications.

PMID- 19573792
TI  - Russia without tobacco.

PMID- 19573793
TI  - Intensive lifestyle changes and health reform.

PMID- 19573794
TI  - Are molecular neuroblastoma classifiers ready for prime time?

PMID- 19573795
TI  - Is the UK ready to embrace HPV testing?

PMID- 19573796
TI  - Total mesometrial resection for cancer of the cervix: the future surgical
      procedure, or oblivion?

PMID- 19573797
TI  - Understanding and preventing local tumour recurrence.

PMID- 19573798
TI  - Uptake in cancer screening programmes.
AB  - For cancer screening programmes to bring about reductions in mortality, a
      substantial proportion of the population must participate. Programmes with low
      uptake can be ineffective and can promote inequalities in health-service
      provision. Strategies to promote uptake are multifaceted, reflecting differences
      in the cancers targeted, invitees, health-service contexts, and the tests
      themselves. Accordingly, there is no universal approach. Strategies should
      accommodate the many factors that can influence uptake and should incorporate the
      need to promote informed choice. Screening has the potential to cause harm, and
      there is an ethical imperative to seek out strategies that provide balanced
      information on cancer screening. Further research is needed to assess newer
      approaches to promoting uptake, such as IT-based programmes, and to identify
      strategies that are balanced, self-sustaining, and affordable.

PMID- 19573799
TI  - Reconstruction after wide excision of primary cutaneous melanomas: part I-the
      head and neck.
AB  - The mainstay of management of primary cutaneous melanoma is wide surgical
      excision, but occassionally a balance is needed between adequately resecting a
      potentially curable lesion and minimising the functional deficit or cosmetic
      deformity in the affected area, particularly in the head and neck region. The
      reconstructive surgeon must have wide knowledge of reconstructive techniques,
      including the advantages and limitations, and a comprehensive understanding of
      the local and regional anatomy if the goals of surgery are to be achieved. In
      part I of this series, we review current literature and available evidence on
      reconstruction after wide excision of primary cutaneous melanoma in the head and
      neck region.

PMID- 19573800
TI  - Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR
      inhibitors.
AB  - The hepatocyte growth factor (HGF)-mesenchymal-epithelial transition factor (MET)
      pathway has a key role in carcinogenesis; it is implicated in proliferation,
      inhibition of apoptosis, angiogenesis, migration, invasiveness, and metastasis.
      All of these molecular events are driven through membrane and intracellular
      coplayers and several downstream effector proteins. MET has been shown to cross
      react with epithelial growth factor receptor (EGFR) proteins and possibly
      substitutes their activity, thus conferring resistance to EGFR-targeting drugs.
      Therefore, identification of MET inhibitors might lead to new treatments for MET
      triggered neoplasia and improve the sensitivity of molecularly targeted
      antineoplastic compounds that are currently in use. In this Review, we outline
      current data regarding the HGF-MET pathway during carcinogenesis and the
      strategies for therapeutic targeting of this pathway. We also discuss the
      rationale and future perspectives of the combinatorial blockade of HGF-MET and
      EGFR signalling cascades in cancer treatment.

PMID- 19573802
TI  - Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal
      polyposis and colorectal cancer caused by germ-line mutations in the adenomatous
      polyposis coli (APC) gene. The term Gardner's syndrome is used to describe
      extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy
      of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive
      fibromatosis), that are especially prominent in families with FAP. We postulate
      that a ciliary dysfunction is the underlying pathogenetic mechanism of
      extraintestinal manifestations in patients with FAP. This postulation is based on
      the presence of common clinical manifestations (ie, cysts, retinal abnormalities,
      and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally,
      both APC and the cilia have degradation of beta-catenin as the common downstream
      target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome
      are clustered in a region encoding a series of amino-acid repeats responsible for
      the binding to beta-catenin. Proofs of principle that beta-catenin could be the
      key mediator of the ciliary disorder also rely in the findings that
      overexpression of beta-catenin induces polycystic kidney disease, and CHRPE
      phenotypes in animal models. Other candidates for the common link between
      Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end
      binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are
      ciliary proteins involved in intraflagellar transport. Finally, pathogenetic
      similarities between some ciliopathies and extraintestinal tumours in FAP suggest
      a cilia defect. Understanding extracolonic manifestations in the context of FAP
      as a ciliary disorder might add new therapeutic options for patients with
      Gardner's syndrome.

PMID- 19573803
TI  - Preserving life and conserving the breast.

PMID- 19573801
TI  - Systemic effects of local radiotherapy.
AB  - Radiotherapy is generally used to treat a localised target that includes cancer.
      Increasingly, evidence indicates that radiotherapy recruits biological effectors
      outside the treatment field and has systemic effects. We discuss the implications
      of such effects and the role of the immune system in standard cytotoxic
      treatments. Because the effects of chemotherapy and radiotherapy are sensed by
      the immune system, their combination with immunotherapy presents a new
      therapeutic opportunity. Radiotherapy directly interferes with the primary tumour
      and possibly reverses some immunosuppressive barriers within the tumour
      microenvironment-ideally, recovering the role of the primary tumour as an
      immunogenic hub. Local radiation also triggers systemic effects that can be used
      in combination with immunotherapy to induce responses outside the radiation
      field.

PMID- 19573804
TI  - Breast cancer SRC activity: bad to the bone.
AB  - Bone metastases are a major cause of breast cancer morbidity and mortality. In
      this issue of Cancer Cell, Zhang and colleagues identify a Src activation
      expression signature associated with late-onset breast cancer bone metastases and
      provide evidence for Src as a key mediator of survival signals in latent bone
      metastases.

PMID- 19573805
TI  - Reflections on miR-ing effects in metastasis.
AB  - In a recent issue of Cell, Valastyan et al. demonstrate that miR-31 can regulate
      multiple steps in the metastatic cascade independent of confounding effects on
      primary tumor development. These data have potential to provide biomarkers for
      prognosis and novel targets for intervention in this most lethal aspect of
      malignancy.

PMID- 19573806
TI  - Actin-based protrusions: promoters or inhibitors of cancer invasion?
AB  - In a recent issue of Cell, Silva and colleagues reported the identification of
      CYFIP1, a member of the actin-assembly-promoting Scar/WAVE complex, as an
      invasion suppressor in epithelial cancers. This study challenges ideas about the
      role of actin in cancer invasion.

PMID- 19573807
TI  - Pancreatic cancer--could it be that simple? A different context of vulnerability.
AB  - In a recent issue of Science, Olive and colleagues document that inhibition of
      Hedgehog (Hh) signaling in a genetically engineered mouse model of pancreatic
      cancer can enhance the intratumor concentration of certain anticancer drugs.
      Could this finding provide us with a new method to attack pancreatic cancer?

PMID- 19573808
TI  - EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of
      cell migration and invasion via a reciprocal regulatory loop with Akt.
AB  - Both pro- and antioncogenic properties have been attributed to EphA2 kinase. We
      report that a possible cause for this apparent paradox is diametrically opposite
      roles of EphA2 in regulating cell migration and invasion. While activation of
      EphA2 with its ligand ephrin-A1 inhibited chemotactic migration of glioma and
      prostate cancer cells, EphA2 overexpression promoted migration in a ligand
      independent manner. Surprisingly, the latter effects required phosphorylation of
      EphA2 on serine 897 by Akt, and S897A mutation abolished ligand-independent
      promotion of cell motility. Ephrin-A1 stimulation of EphA2 negated Akt activation
      by growth factors and caused EphA2 dephosphorylation on S897. In human
      astrocytoma, S897 phosphorylation was correlated with tumor grades and Akt
      activation, suggesting that the Akt-EphA2 crosstalk may contribute to brain tumor
      progression.

PMID- 19573809
TI  - AKT-independent signaling downstream of oncogenic PIK3CA mutations in human
      cancer.
AB  - Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway
      occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene
      mutations both direct PI3K-dependent tumorigenesis largely through activation of
      the AKT/PKB kinase. However, here we show through phosphoprotein profiling and
      functional genomic studies that many PIK3CA mutant cancer cell lines and human
      breast tumors exhibit only minimal AKT activation and a diminished reliance on
      AKT for anchorage-independent growth. Instead, these cells retain robust PDK1
      activation and membrane localization and exhibit dependency on the PDK1 substrate
      SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA mutant cancer
      cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT
      independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could
      inform rational therapeutics in cancers harboring PIK3CA mutations.

PMID- 19573810
TI  - Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx
      mutations that prevent modifications by DNA-damage-activated kinases.
AB  - Mdmx is a critical negative regulator of the p53 pathway that is
      stoichiometrically limiting in some tissues. Posttranslational modification and
      degradation of Mdmx after DNA damage have been proposed to be essential for p53
      activation. We tested this model in vivo, where critical stoichiometric
      relationships are preserved. We generated an Mdmx mutant mouse in which three
      conserved serines (S341, S367, S402) targeted by DNA-damage-activated kinases
      were replaced by alanines to investigate whether modifications of these residues
      are important for Mdmx degradation and p53 activation. The mutant mice were
      remarkably resistant to radiation, and very susceptible to Myc-induced
      lymphomagenesis. These data demonstrate that Mdmx downregulation is crucial for
      effective p53-mediated radiation responses and tumor suppression in vivo.

PMID- 19573811
TI  - Proteasomal and genetic inactivation of the NF1 tumor suppressor in
      gliomagenesis.
AB  - Loss-of-function mutations in the NF1 tumor suppressor result in deregulated Ras
      signaling and drive tumorigenesis in the familial cancer syndrome
      neurofibromatosis type I. However, the extent to which NF1 inactivation promotes
      sporadic tumorigenesis is unknown. Here we report that NF1 is inactivated in
      sporadic gliomas via two mechanisms: excessive proteasomal degradation and
      genetic loss. NF1 protein destabilization is triggered by the hyperactivation of
      protein kinase C (PKC) and confers sensitivity to PKC inhibitors. However,
      complete genetic loss, which only occurs when p53 is inactivated, mediates
      sensitivity to mTOR inhibitors. These studies reveal an expanding role for NF1
      inactivation in sporadic gliomagenesis and illustrate how different mechanisms of
      inactivation are utilized in genetically distinct tumors, which consequently
      impacts therapeutic sensitivity.

PMID- 19573814
TI  - Clinical commentary regarding endometrial cancer and lymphadenectomy.

PMID- 19573812
TI  - Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal
      microenvironment.
AB  - Notch1 is a proto-oncogene in several organs. In the skin, however, Notch1
      deletion leads to tumor formation, suggesting that Notch1 is a "tumor suppressor"
      within this context. Here we demonstrate that, unlike classical tumor
      suppressors, Notch1 loss in epidermal keratinocytes promotes tumorigenesis non
      cell autonomously by impairing skin-barrier integrity and creating a wound-like
      microenvironment in the skin. Using mice with a chimeric pattern of Notch1
      deletion, we determined that Notch1-expressing keratinocytes in this
      microenvironment readily formed papillomas, showing that Notch1 was insufficient
      to suppress this tumor-promoting effect. Accordingly, loss of other Notch
      paralogues that impaired the skin barrier also predisposed Notch1-expressing skin
      to tumorigenesis, demonstrating that the tumor-promoting effect of Notch1 loss
      involves a crosstalk between barrier-defective epidermis and its stroma.

PMID- 19573815
TI  - Practical tips for office hysteroscopy and second-generation "global" endometrial
      ablation.
AB  - Hysteroscopy and endometrial ablation using the second-generation devices are
      safe, generally well tolerated, and effective when performed in the medical
      office as opposed to the ambulatory surgery center or hospital operating room.
      Not only does this benefit the patient and physician in terms of convenience and
      cost savings, and the overall economic benefit to the health care system is
      great. The availability of modern hysteroscopic and video equipment, the advent
      of second-generation "global"endometrial ablation devices, and use of minimal
      sedation combined with effective local anesthesia have made office procedures
      possible. Several states have enacted specific regulations and requirements for
      office based surgery. It is incumbent on the physician to be aware of which local
      regulations are applicable and the level of procedure he or she is willing to
      perform before embarking on an office-based surgery program. The AAGL ListServ
      discussion forum provides members with an invaluable source of clinical opinion
      about patient care issues in minimally invasive gynecology. These opinions come
      from experts around the world representing both academic centers and clinical
      practice who respond to questions or issues posed by colleagues. This review
      discusses each of the second-generation endometrial ablation devices in detail
      and some of the more pertinent issues related to office hysteroscopy and global
      endometrial ablation that were posted on the ListServ. Rollerball and
      transcervical resection of the endometrium are not discussed because the
      overwhelming majority of these procedures are performed in the operating room and
      there is little potential for their becoming office procedures. Practical
      clinical tips based on the evidence in the literature are discussed.

PMID- 19573813
TI  - Latent bone metastasis in breast cancer tied to Src-dependent survival signals.
AB  - Metastasis may arise years after removal of a primary tumor. The mechanisms
      allowing latent disseminated cancer cells to survive are unknown. We report that
      a gene expression signature of Src activation is associated with late-onset bone
      metastasis in breast cancer. This link is independent of hormone receptor status
      or breast cancer subtype. In breast cancer cells, Src is dispensable for homing
      to the bones or lungs but is critical for the survival and outgrowth of these
      cells in the bone marrow. Src mediates AKT regulation and cancer cell survival
      responses to CXCL12 and TNF-related apoptosis-inducing ligand (TRAIL), factors
      that are distinctively expressed in the bone metastasis microenvironment. Breast
      cancer cells that lodge in the bone marrow succumb in this environment when
      deprived of Src activity.

PMID- 19573816
TI  - Hysteroscopic identification of hydatidiform mole.

PMID- 19573817
TI  - Asymptomatic abdominal wall hernias and incidental diagnoses during gynecologic
      surgeries.

PMID- 19573818
TI  - Laparoscopy vs minilaparotomy in women with symptomatic uterine myomas: a
      prospective randomized study.
AB  - OBJECTIVE: To compare outcomes in patients with symptomatic uterine myomas who
      underwent laparoscopic (LPS) or minilaparotomic (MLPT) myomectomy. DESIGN:
      Prospective randomized study (Canadian Task Force classification II-2). SETTING:
      University hospital. PATIENTS: Eighty patients with no more than 3 uterine myomas
      of maximal diameter of 7 cm. INTERVENTION: Either LPS or MLPT myomectomy.
      MEASUREMENTS AND MAIN RESULTS: Mean blood loss, mean duration of postoperative
      ileus, and mean decrease in hemoglobin were significantly lower in the LPS
      compared with the MLPT group (p < .001). Mean operative time was not
      significantly longer in the LPS group compared with the MLPT group. Duration of
      hospitalization was significantly shorter in the LPS compared with the MLPT group
      (p < .001). No intraoperative complications were observed during MLPT. In 1
      patient, conversion from LPS to MLPT was necessary because of difficulty in
      reconstructing the uterine wall. CONCLUSION: Laparoscopic myomectomy is a
      suitable alternative to MLPT in women with 1 to 3 myomas. However, preoperative
      careful evaluation of the size and sites of the myomas is necessary to avert
      conversion and prevent complications.

PMID- 19573819
TI  - Hysteroscopic surgery of ectopic pregnancy in the cesarean section scar.
AB  - STUDY OBJECTIVE: To evaluate the effect of hysteroscopy in the treatment of
      caesarean section scar pregnancy. DESIGN: Retrospective review. PARTICIPANTS:
      Thirty-nine patients with cesarean scar pregnancy. INTERVENTIONS: Between January
      2006 and June 2008, 39 patients with caesarean section scar pregnancy underwent
      hysteroscopic removal of conceptive tissues in our department. Their medical
      records were reviewed retrospectively. MEASUREMENTS AND MAIN RESULTS: The
      diagnosis was confirmed by serum human chorionic gonadotropic concentration and
      at ultrasonographic or magnetic resonance imaging. All patients underwent
      hysteroscopic removal of conceptive tissues under ultrasonographic guidance.
      Before surgery, 36 patients received 25 mg of oral mifepristone, 25 mg, twice a
      day for 3 days, and 3 patients received an injection of methotrexate salt, 50 mg,
      and underwent preoperative bilateral uterine artery embolization. Results were
      reported as good in 37 patients; only 2 patients required additional surgery.
      CONCLUSION: Hysteroscopic removal of conceptive tissues implanted in a cesarean
      section scar seems to be a feasible and safe procedure that might be considered
      as a treatment option.

PMID- 19573820
TI  - Contrast-tuned imaging and second-generation contrast agent SonoVue: a new
      ultrasound approach to evaluation of tubal patency.
AB  - STUDY OBJECTIVE: To determine whether transvaginal hysterosalpingo-contrast
      sonography (HyCoSy) with a new dedicated contrast-enhanced ultrasound technique,
      can contribute to accurate diagnosis of tubal occlusion. DESIGN: Prospective
      observational study (Canadian Task Force classification II-2). SETTING:
      University hospital. PATIENTS: Two-hundred twelve patients with primary or
      secondary infertility. INTERVENTIONS: All patients underwent transvaginal HyCoSy.
      If the tubes showed no evidence of patency after injection of air-saline
      solution, a solution with sulphur hexafluoride bubbles (SonoVue) was injected
      into the uterine cavity and tubes while contrast-tuned imaging (CnTI) was
      applied. Patients with tubal occlusion underwent laparoscopic chromoperturbation.
      MEASUREMENTS AND MAIN RESULTS: Of the 212 patients who underwent tubal
      insufflation with air-saline solution, 52 demonstrated tubal occlusion, bilateral
      in 21 patients and unilateral in 31 patients, for a total of 73 suspected
      occluded tubes. At the HyCoSy test with SonoVue and CnTI, only 47 tubes seemed to
      be occluded, and in the other 26 tubes, passage of SonoVue was observed. HyCoSy
      with Sono Vue demonstrated high concordance for tubal obstruction with the
      laparoscopic dye test (94%). CONCLUSIONS: HyCoSy with SonoVue and CnTi is a low
      acoustic pressure technique in which bubbles are not immediately destroyed and
      can be detected for several minutes. This enables the signal sent to the
      equipment to be filtered from the echoes emanating from other tissues. Therefore,
      excluding the fundamental image, the bubbles are clearly observed, with no
      visualization of pelvic tissues and organs. This allows easier evaluation of
      tubal patency, provides a more accurate assessment of tubal occlusion, and
      enables better visualization of the tubal course.

PMID- 19573821
TI  - Ultrasound detection of the "sliding viscera" sign promotes safer laparoscopy.
AB  - STUDY OBJECTIVE: To estimate the feasibility of preoperative ultrasound
      evaluation of the umbilical region in patients undergoing laparoscopy with a
      previous history of abdominal surgery. DESIGN: Prospective study (Canadian Task
      Force Classification II-1). SETTING: Department of Obstetrics and Gynecology
      Fatebenefratelli Isola Tiberina Hospital. PATIENTS: Twenty-five women with a
      previous history of open abdominal surgery (group A) and a group of 22 women with
      no previous history of surgery (group B) underwent dynamic ultrasound evaluation
      of the umbilical field. INTERVENTION: Ultrasound Slide-By test. RESULTS: Patients
      were asked to take a deep inspiratory breath, which accentuated respiratory
      excursion. The movement of the intraabdominal contents in a vertical fashion in
      relation to the abdominal wall, referred to as the "viscera slide," between the
      bowel and peritoneum was evaluated. Abdominal wall tissue thickness, Uracus to
      peritoneum thickness (UTP, mm) were also evaluated. Non parametric Mann-Whitney
      testing was used. No major demographic differences between the 2 study groups was
      noted. The abdominal wall tissue thickness was not significantly different
      between the 2 groups. The UTP was shorter in A group than in B group (1.5 +/- 0.3
      mm vs 3.5 +/- 0.9 mm, p = .002). Absence of the "sliding viscera" sign was
      observed in 16 patients in group A and in 1 patient in group B. Patients with an
      absence of the sliding viscera sign were found to have subumbilical fibrous
      adhesions during laparoscopy. CONCLUSIONS: Evaluation of trocar insertion sites
      may be difficult and remains a challenge for peritoneal endosurgical access. We
      have shown that absence of the "sliding viscera" sign is more likely to be linked
      to subumbilical adhesions and represents a quick method for preoperative
      assessment. The UTP may also be a useful measurement, which requires further
      validation.

PMID- 19573822
TI  - Adverse obstetric outcomes at term after hysteroscopic metroplasty.
AB  - STUDY OBJECTIVE: To estimate obstetrical complications at term after
      hysteroscopic metroplasty for septate uterus. DESIGN: A retrospective comparative
      study (Canadian Task Force classification II-2). SETTING: La Conception Hospital,
      Department of Obstetrics and Gynecology, Marseille, France. PATIENTS AND
      INTERVENTIONS: Thirty-one women who had a term pregnancy from January 1996
      through December 2004 after hysteroscopic metroplasty for septate uterus (group
      A) were studied retrospectively. A control group (group B) of 62 women was
      selected from the same database who had term pregnancies and no history of
      hysteroscopic metroplasty. MEASUREMENTS AND MAIN RESULTS: Obstetric complications
      at term and neonatal outcomes after hysteroscopic metroplasty were compared
      between 2 groups. The rate of fetal malpresentation was significantly higher in
      group A versus group B (11/31 [35.5%] vs 0/62, p < .001). Mean birth weight was
      significantly lower in group A versus group B (2940 g +/- 52 vs 3266 g +/- 456, p
      =.002). The rate of caesarean section was significantly higher in group A versus
      group B (19/31 [61.3%] vs 4/62 [6.4%], p < .001). CONCLUSION: The results of this
      study suggest that patients with a previous hysteroscopic metroplasty for septate
      uterus are at increased risk for fetal malpresentation at term, low birth weight
      infants, and delivery by caesarean section and should therefore be informed of
      these risks before delivery.

PMID- 19573823
TI  - Prevalence, 1-year regression rate, and clinical significance of asymptomatic
      endometrial polyps: cross-sectional study.
AB  - STUDY OBJECTIVE: To estimate the prevalence, 1-year regression rate, and clinical
      significance of endometrial polyps in women aged 45 to 50 years. DESIGN: Cross
      sectional study (Canadian Task Force II-2). SETTING: University teaching
      hospital. PATIENTS: Two hundred fifty-seven of 1000 randomly selected women aged
      45 to 50 years. INTERVENTIONS: Transvaginal ultrasonography and saline infusion
      sonography were performed in all study participants and were repeated in women
      with endometrial polyps after 12 months. Polyps present at follow-up were removed
      by hysteroscopic polyp resection. MEASUREMENTS AND MAIN RESULTS: Endometrial
      polyps were diagnosed in 31 women (12.1%). At 1 year, the polyp regression rate
      was 27%. Myomas occurred more often in women with endometrial polyps, and women
      with polyps experienced significantly heavier periodic bleeding compared with
      women without polyps. CONCLUSION: Our study findings suggest that endometrial
      polyps are common in women aged 45 to 50 years and that women with such polyps
      experience heavier periodic bleeding. Although some polyps seem to regress
      spontaneously during 1-year follow-up, most seem to persist.

PMID- 19573824
TI  - Should the gynecologist perform laparoscopic bowel resection to treat
      endometriosis? Results over 7 years in 168 patients.
AB  - STUDY OBJECTIVE: To assess the feasibility and safety of laparoscopic bowel
      resections for endometriosis performed by gynecologic surgeons. DESIGN:
      Retrospective cohort study (Canadian Task Force Classification II-3). SETTING:
      Fertility and pelvic surgery clinics. PATIENTS: One hundred sixty-eight women
      (age 21-53 years) with symptoms including pelvic pain, infertility, or both with
      252 bowel endometriotic lesions underwent laparoscopic bowel resection performed
      by gynecologic surgeons between May 2000 and January 2008. INTERVENTIONS:
      Laparoscopic procedures for excision of several endometriotic nodes and lesions
      included shaving resection (LscShR), discoid resection (LscDR), segmental
      resection (LscSgR), terminal ileal resection (LscIR), partial cecal resection
      (LscCR), and appendectomy (LscAp). MEASUREMENTS AND MAIN RESULTS: The 168
      patients underwent 172 laparoscopic bowel resections (4 patients were operated on
      twice) by the same surgeon. Lesions were distributed as follows: 133 (79%) in the
      rectum, 61 (24%) in the sigmoid colon, 47 (19%) in the appendix, 5 (2%) in the
      terminal ileum, 3 (1%) in the descending colon, and 3 (1%) in the cecum. At
      surgeon discretion, 12 lesions were not resected. A total of 216 bowel procedures
      were necessary to remove the 240 lesions include shaving resection in 22 patients
      (10%), discoid resection in 52 (24%), segmental resection in 92 (42%), terminal
      ileal resection in 2 (1%), partial cecal resection in 1 (0.6), and appendectomy
      in 47 (22%). Major complications occurred in 13 patients (7.6%) and included
      rectovaginal fistula in 3 patients (1.7%), rectosigmoid anastomosis dehiscence
      and bowel occlusion in 1 patient each (0.6%), and persistent bowel dysfunction in
      4 patients (2.3%). These results are comparable to those reported in the
      literature to date. Complete relief of symptoms (measured using the Visick scale)
      was noted in patients with dysmenorrhea (59%), dyspareunia (75%), noncyclic
      pelvic pain (90%), pain on defecation (100%), constipation (83%), and cyclic
      rectal bleeding (100%). CONCLUSION: Surgery to treat bowel endometriosis can be
      safely and efficiently performed by the gynecologic pelvic surgeon. Meticulous
      training and a multidisciplinary approach to comprehensive operative care are
      necessary. These findings can be validated by prospective collaborative studies
      and reports from other surgeons.

PMID- 19573825
TI  - The levonorgestrel intrauterine system is an effective treatment in women with
      abnormal uterine bleeding and anticoagulant therapy.
AB  - OBJECTIVE: To evaluate the efficacy of levonorgestrel intrauterine systems (LNG
      IUS) in obese women with AUB on anticoagulant therapy. DESIGN: Prospective
      observational case series (Canadian Task Force Classification II-3). SETTING:
      University affiliated teaching hospital. PATIENTS: Premenopausal women on
      Warfarin therapy. INTERVENTIONS: From January 2002 through January 2007, 10 women
      were identified from the senior author's clinical practice (G.A.V.). After
      clinical assessment, including Papanicolaou smear, endometrial biopsy, and pelvic
      sonography, the LNG-IUS was placed to treat their AUB. MEASUREMENTS AND MAIN
      RESULTS: The median and range of age, parity, and body mass index were 45 years
      (34-49), 1 (0-4), and 38 kg/m(2) (26-52), respectively. All women were receiving
      warfarin therapy (4-12.5 mg/d) for previous venous thromboembolism. Some patients
      had additional comorbid conditions and were at high risk for traditional medical
      or surgical therapies. After placement of the LNG-IUS, all women reported
      menstrual reduction at 3 and 6 months. By 12 months, 1 woman with large fibroids
      expelled the LNG-IUS and was treated with transfemoral uterine artery
      embolization. Two women had amenorrhea, and 7 had hypomenorrhea. At 2 to 5 years,
      1 woman expelled the LNG-IUS and hysterectomy indicated extensive adenomyosis in
      a 195-g uterus, and 1 woman had hysteroscopic endometrial ablation, 4 were
      menopausal, 2 had amenorrhea, and 1 had hypomenorrhea. In the 5 women with
      uterine fibroids measuring 4.2 to 147 cm(3), the fibroids were reduced in volume
      by approximately 75% in 2, were no longer detectable in 1, were subsequently
      shown to be adenomyoma in 1, and required uterine artery embolization in 1.
      CONCLUSION: In properly assessed and selected obese, premenopausal women with AUB
      receiving warfarin therapy and at high risk for traditional therapies, the LNG
      IUS was an effective treatment in 70% of patients.

PMID- 19573826
TI  - Hysteroscopic management of residual trophoblastic tissue and reproductive
      outcome: a pilot study.
AB  - We report on the feasibility, efficiency, and reproductive outcomes of
      hysteroscopic resection of late residual trophoblastic tissue in 50 patients in
      an observational study over 6 years. Complete evacuation of the uterus was
      achieved in all patients by hysteroscopy. The median operative time was 21 (15
      30) min. Only one surgical complication was registered: a uterine perforation in
      a patient with previous metroplasty. Hysteroscopic resection of persistent
      trophoblastic tissue seems to be a safe and efficient procedure that could be
      proposed as an alternative to conventional non-selective blind curettage. We
      would also recommend systematic second-look hysteroscopy to asess the exact
      prevalence of post-procedure intrauterine adhesions.

PMID- 19573827
TI  - Delayed staple erosion into the bladder after removal of a benign ovarian mass.
AB  - We describe the case of a 54-year-old woman who presented with an ovarian mass in
      September 2000. The patient remained asymptomatic for 4 years until she developed
      a persistent urinary tract infection and hematuria. After a computed tomographic
      scan of the pelvis revealed urolithiasis, the secondary finding of potential
      staple erosion via cystoscopy was realized. Delayed staple erosion rarely occurs
      and can result in detrimental patient outcome. The diagnosis and management of
      this unusual complication are documented.

PMID- 19573828
TI  - Repair of uterine rupture in twin gestation after laparoscopic cornual resection.
AB  - Spontaneous uterine rupture in the course of pregnancy is a rare event that
      usually occurs in a scarred uterus. The event occurs mostly during the
      intrapartum period and is potentially catastrophic for both mother and fetus. We
      report a case of 2-cm cornual rupture in a pregnant woman at 13 weeks twin
      gestation with previous history of cornual pregnancy successfully managed via
      laparoscopy. Sudden onset of abdominal pain and vaginal bleeding was noted first.
      Physical examination revealed stable vital signs, lower abdominal tenderness, and
      mild rebounding pain. Pelvic ultrasonography revealed twin pregnancy at 13 weeks
      with extrauterine saccular structure 6 cm in diameter located on the left fundus
      and contiguous with an intrauterine oligohydramnics twin. Exploratory laparotomy
      was promptly performed, and a small rupture about 2 cm in diameter was observed
      on the upper portion of the left fundus, the site of a previous laparoscopic
      cornual resection scar. A protruding amniotic sac of about 6 cm diameter and
      containing some part of the umbilical cord was seen. The uterine rupture site was
      repaired directly after aspiration of amniotic fluid from the protruding sac.
      After surgery, the patient received antibiotics, 17-OH-progesterone for potential
      rupture of membranes and prematurity. Tocolysis with Ritodrine for irregular
      uterine contractions was given at 22 weeks gestation. Steroids were given at 24
      weeks gestation. The pregnancy ended with a successful delivery by cesarean
      section because of uncontrollable uterine contractions at 30 5/7 weeks gestation.
      In conclusion, although termination of pregnancy would normally be recommended
      when uterine rupture occurs, a different approach to management may now be
      accepted.

PMID- 19573829
TI  - Vaginal myoma expulsion after NovaSure endometrial ablation.
AB  - A 46-year old multiparous woman visited a 1-stop clinic for abnormal uterine
      bleeding. There was a small submucosal type 2 myoma of 2 cm in her normal sized
      uterus. We treated her using Novasure endometrial ablation. One year later the
      patient suffered from sudden excessive vaginal bleeding and collapse. A myoma of
      4 cm was being expelled from the uterus.

PMID- 19573830
TI  - Giant endocervical polyp mimicking cervical malignancy: primary excision and
      hysteroscopic resection.
AB  - Giant cervical polyps are characterized by an unusually large size and appear
      clinically as malignant. A 35-year-old woman had increased vaginal discharge and
      lower abdominal discomfort. At examination, a fist-sized, hard, consistent mass
      was found in the vagina. Pelvic magnetic resonance imaging revealed a 12.6 x 8-cm
      solid tumor with internal papillary growth within the entire vaginal cavity. The
      tumor base was suspected to have originated from the endocervix by a connecting
      stalk. Primary excision of the tumor was performed via the vagina, and the
      remnant tissue was completely removed at hysteroscopic resection. The final
      histopathologic findings confirmed a benign giant cervical polyp.

PMID- 19573831
TI  - Reduction by 98% in uterine myoma volume associated with significant symptom
      relief after peripheral treatment with magnetic resonance imaging-guided focused
      ultrasound surgery.
AB  - Magnetic resonance imaging-guided focused ultrasound surgery is a noninvasive
      treatment for symptomatic uterine myomas. Previous studies have demonstrated a
      correlation between the treated volume of the myoma, improvement in symptoms, and
      lesion shrinkage. We report a case in which MRgFUS treatment only at the
      periphery of the myoma resulted in a 98% reduction in tumor volume at 8 months
      posttreatment, and at 12-month follow-up, only a small lesion was visible at
      magnetic resonance imaging. The patient's symptoms, as assessed using the Uterine
      Fibroids Symptom and Quality of life (UFS-QOL) questionnaire, were substantially
      improved at both 6 and 12 months posttreatment. We also provide a hypothesis to
      explain this dramatic reduction in myoma volume after only partial MRgFUS
      treatment of the lesion.

PMID- 19573832
TI  - A rare case of large epididymal cyst in androgen insensitivity syndrome removed
      laparoscopically.
AB  - Androgen insensitivity syndrome is a disorder of sexual differentiation with 46XY
      karyotype. The gonad is at risk (33% by 50 years of age) for development of
      malignant tumors. Hence, gonadectomy is warranted. We present a case of a 22-year
      old woman diagnosed with androgen insensitivity syndrome during investigation of
      primary amenorrhea. Ultrasonography showed intraabdominally-located gonads, with
      a large, nontender cyst of 9.2 x 5.6 x 5.4 cm size, with limited mobility, to the
      right of the midline. There was also a partial septum, with a wall thickness of 1
      to 2 mm and containing clear fluid. Because of suspicion of malignancy, complete
      surgery including laparoscopic peritoneal cytologic study, gonadectomy,
      lymphadenectomy, and omentectomy were performed. Histopathologic study showed
      testis with an epididymal cyst. Formation of epididymal cyst is rare in these
      cases. The patient did well in the postoperative period. She was put on hormone
      replacement therapy and is doing well.

PMID- 19573833
TI  - A leiomyoma presenting as an exophytic periurethral mass: a case report and
      review of the literature.
AB  - Periurethral masses in females are rarely observed, although they can occur
      anywhere along the genitourinary tract. They may be detected on physical
      examination or present with symptoms such as vaginal swelling, bladder outlet
      obstruction, vaginal bleeding, hematuria, or urinary tract infection. We report a
      sexually inactive, 27-year-old woman with an exophytic, fimbria-like periurethral
      mass. The benign nature of the lesion was suspected on the basis of the findings
      of magnetic resonance imaging. Surgical enucleation was performed. The
      microscopic examination revealed a urethral leiomyoma. Immunohistochemical study
      confirmed a leiomyoma with positive staining for smooth muscle actin and negative
      staining for S-100.

PMID- 19573834
TI  - Uterine vein rupture at delivery as a delayed consequence of laparoscopic surgery
      for endometriosis: a case report.
AB  - Laparoscopic resection of deep infiltrating endometriosis (DIE) has been reported
      to be an effective method for reduction of endometriosis-associated pain. As its
      complications, bowel perforation, urinary tract injury and neurogenic bladder are
      well known; however, uterine vein rupture during pregnancy has not been reported
      previously. We encountered a case of hemoperitoneum resulting from uterine vein
      rupture at a delivery as a delayed consequence of laparoscopic resection of DIE.
      A 31-year-old, para 2 woman underwent laparoscopic resection of lateral pelvic
      peritoneum, uterosacral ligaments, and bilateral endometriomas, exposing uterine
      vessels, which we covered with fibrin glue. Endometriosis-associated pain
      disappeared, and then the patient conceived 4 months later. The course of
      pregnancy and induction of labor with controlled oxytocin infusion was
      uneventful, and the patient delivered a female baby without asphyxia. Immediately
      after delivery, low abdominal pain with hypotension occurred despite absence of
      abnormal vaginal bleeding. Ultrasonography and the blood hemoglobin value
      suggested hemorrhagic shock owing to hemoperitoneum; therefore emergency
      exploratory laparotomy was performed. Active bleeding was found at the right
      uterine vein, which was then sutured for hemostasis. The patient received a blood
      transfusion and recovered without any problems. The bleeding lesion was located
      at the vein on which the peritoneum had been removed at the first laparoscopy,
      which suggested that the operation for DIE included a risk of uterine vessel
      rupture during pregnancy.

PMID- 19573835
TI  - Postoperative pubic symphysis osteomyelitis after laparoscopic two-team sling
      with anterior and posterior colporrhaphy.
AB  - A 53 year-old woman, who previously had a Burch colposuspension, developed
      osteomyelitis of the pubic symphysis about 1 month after undergoing a
      laparoscopic 2-team sling with anterior and posterior colporrhaphy. The diagnosis
      was made on the basis of computed tomography-guided aspiration of the pubic
      symphysis, which was positive for group B Streptococcus sp. To our knowledge,
      this is the first case report of osteomyelitis after a laparoscopic retropubic
      sling procedure. Osteomyelitis is a rare postoperative complication in female
      pelvic reconstructive surgery but has been reported in cases where the pubic bone
      is used for anchoring. It is especially unusual in this case because the pubic
      symphysis was not used for securing the sling.

PMID- 19573836
TI  - Blunt vascular trauma can be a consequence of robotic surgeries.

PMID- 19573837
TI  - A survey of sued physicians' self-reported reactions to malpractice litigation in
      Iran.
AB  - OBJECTIVE: To illustrate the psychological effect of grievances and negligence
      litigation on doctors sued by Legal Medicine Organization Complaints Commissions.
      METHODS: Retrospective survey regarding the views of a large sample of Iranian
      sued physicians by using a piloted anonymous questionnaire. RESULTS: The answer
      rate was 77.5%. Seventy-six per cent of participants encountered monitoring
      criteria for psychiatric disturbance. Rate of psychological morbidity in between
      study cluster was much higher than Iranian general population, Iranian non-sued
      general practitioners, interns and medical students. There was, however, minimal
      dysfunction of work, public or family life. The survey form to estimate the
      doctor's realization of lawful risk displayed that doctors yet misconceive medico
      legal risk. Doctors being sued or having legal protests against them depict the
      process as an exceedingly demanding event. CONCLUSIONS: Grievance or legal action
      is unusual in the daily practice of doctors, but in today's medico-legal domain
      they face a continuous possible threat. The threat of, or real, legal process can
      cause psychological, corporeal and behavioral practice changes.

PMID- 19573838
TI  - Fatal unintentional injuries among young children--a hospital based retrospective
      analysis.
AB  - Unintentional (accidental) injuries in childhood constitute a significant public
      health problem. Young children are extremely vulnerable to unintentional injuries
      that are vastly preventable. All cases of fatal unintentional injuries in
      children aged 10 years and below autopsied during 1994-2007 were retrospectively
      reviewed. Seventy five such cases were identified during the 14 year study
      period. Males accounted for 68% of cases with a male-female ratio of 2.1:1. Mean
      age of male and female victims was 5.3 and 4.9 years, respectively. Road traffic
      fatalities accounted for majority of the cases in this age group (52%), followed
      by those due to thermal injuries (22.7%). Flame was the cause of thermal injuries
      in 52.9% cases and scalds were observed in 47.1% cases. Traffic fatalities, fall
      and drowning were more common in school age children while toddlers and pre
      school age children were relatively at a greater risk from domestic accidents
      (thermal injuries and poisoning). The most frequent victims of road traffic
      incidents were pedestrians (64.1%). Head injuries alone were the cause of
      fatalities in the majority of road traffic incidents (82.1%). The study
      highlights on the pattern of fatalities due to unintentional injuries among young
      children. To reduce the burden of unintentional childhood mortalities in this
      region, priorities for school age children are traffic injuries and for toddlers
      and pre-school children, thermal injuries.

PMID- 19573839
TI  - Aluminum phosphide fatalities at mild exertion in asymptomatic children: a clue
      to understand the variations of the autopsy findings.
AB  - Fatalities resulted from aluminium phosphide (ALP) intoxication in completely
      healthy children with no preceded clinical sings or symptoms were presented. Data
      regarding circumstances, autopsy reports, histopathological examination,
      toxicological investigation, and police enquiries were also collected and
      evaluated. The affected children were females, and 6-16 years old. They were
      completely healthy and died suddenly in relation to some physical activities such
      as running, walking, and bathing, without any prior complain. The viscera showed
      intense congestion with moderate to severe pulmonary edema. The cause of the
      sudden termination of life in the reported cases is mostly cardiac ones. Physical
      exertion may precipitate death due to increased cardiac stress, increased oxygen
      demand, and by aggravating metabolic acidosis. The absence of clinical symptoms
      before death may be due to the low level ALP, or due to the occurrence of death
      in the early stages after exposure to poison. Death due to ALP could result in
      cases of mild, moderate, or severe ALP intoxication. This may explain partly the
      differences encountered in clinical, autopsy, and histopathology findings of ALP
      intoxication. Fatalities are not the mere consequences of the dose of the poison,
      but factors such as physical activity and low oxygen level may be quite
      important.

PMID- 19573840
TI  - A new classification of necrophilia.
AB  - Necrophilia is a paraphilia whereby the perpetrator gets sexual pleasure in
      having sex with the dead. Most jurisdictions and nations have laws against this
      practice. Necrophilia exists in many variations, and some authors have attempted
      to classify necrophilia. However many related terms such as pseudonecrophilia
      continue being used differently by different authors, necessitating the
      introduction of a new classification system. The classification system suggested
      by the author attempts to put all different shades of necrophilia under 10
      classes.

PMID- 19573841
TI  - Electrolyte analysis of pleural effusion as an indicator of drowning in seawater
      and freshwater.
AB  - It is important for forensic pathologists to determine the diagnosis of drowning
      as well as the site of drowning. In a previous study, we propose that analysis of
      electrolytes in pleural effusion from rats may be useful for determining whether
      drowning has occurred in seawater or freshwater. To test this proposal, we
      measured the concentration of sodium, potassium and chloride ions and total
      protein in pleural effusion from 40 autopsy cases: 24 involving seawater
      drowning, 9 freshwater drowning and 7 no drowning. The concentrations of sodium
      and chloride ions in pleural effusion showed a significant difference between
      seawater drowning and freshwater drowning. The concentration of potassium ions
      and total protein showed no difference between each group, although they
      increased in proportion to the postmortem interval in cases of both seawater and
      freshwater drowning. These results are almost same as our previous study and,
      thus, the quantitative analysis of electrolytes in pleural effusion may be useful
      for determining whether drowning has occurred in seawater or freshwater.

PMID- 19573842
TI  - Firearm-related deaths in Brescia (Northern Italy) between 1994 and 2006: a
      retrospective study.
AB  - This retrospective study analyzes post-mortem examination data of 164 firearm
      related casualties recorded by the Brescia, Italy Institute of Forensic Medicine
      between the years 1994 and 2006. The following variables were considered: year,
      month and day of death, gender and age of the victim, manner of death (homicide,
      suicide, accidental), type of weapon used, anatomical site and number of wounds,
      scene of death, and, whenever requested by the local District Attorney's Office,
      results of the toxicological examinations conducted on the corpses of the
      deceased. In the County of Brescia, Italy, the 2006 firearm-related mortality
      rate amounted to 0.84 per 100,000 residents, with an average of 12.6 cases per
      year. The most common manner of death was suicide (60.4%), followed by homicide
      (35.9%) and accidental death (3.7%). Most victims were male, with an average age
      of 47.2 in cases of suicide, 37.9 in cases of homicide, and 47.5 in cases of
      accidental death. Considering all of the death manners contemplated in this
      study, the weapon types most frequently resorted to were single-action, short
      barrelled guns, followed by multiple-action, long-barrelled ones. In cases of
      suicide, entry wounds were primarily situated on the head (right temple) and
      chest (precordium), while in cases of homicide no conclusions could be drawn as
      to the entry wounds' predominant location.

PMID- 19573843
TI  - The medico-legal scene in Dubai: 2002-2007.
AB  - Various characteristics of the medico-legal scene in Dubai are described, along
      with an overview of all cases examined over a period of 6 years. During the
      period of study, a total of 17,683 cases were examined in the Department of
      Forensic Medicine of Dubai Police General Headquarters. This constituted a yearly
      average of (2947.16). The average annual increment was 11.13%, the percentage of
      increase between 2002 and 2007 being 68.96%. Of these 10,165 (57.48%) were
      clinical cases of injuries, 5404 (30.56%) postmortem examinations, 1525 (8.62%)
      clinical cases of sexual crimes, 409 (2.3%) age estimations, 58 (0.32%) medical
      responsibility, 20 (0.11%) criminal abortion, 61 (0.34%) civil actions and 38
      (0.21%) miscellaneous cases. Of postmortem examinations, 4846 (89.7%) of them
      were males and 558 (10.3%) females. The age ranged from (0-90) years, with a mean
      age of 40.5 years. The peak incidence was in the age group (20-50) years, where
      the extremes of age were least represented (Fig. 1). Only in 361 cases (6.68% of
      the grand total) the deceased was a local citizen. Autopsies amounted to 394
      cases, which constituted 7.29% of the total deaths examined. The four manners of
      death in descending order of frequency were natural 3003 (55.57%), accidental
      1727 (32%), suicidal 498 (9.2%), homicidal 164 (3%). The manner was undetermined
      in 12 (0.22%) of the cases over the 6 year period.

PMID- 19573844
TI  - Suicide in people over 65 years of age in the Australian Capital Territory.
AB  - Suicide by hanging is not an uncommon event in people over the age of 65 years in
      the Australian Capital Territory. We will review the incidence of suicide over
      the last seven years, as well as discuss the characteristics of suicide in
      elderly people. Knowledge of local suicide patterns enables the forensic medical
      officer to recognise deaths that may be unexpected or unusual.

PMID- 19573845
TI  - Lethal head entrapment--a problem characteristic of early childhood.
AB  - Accidental deaths in infancy and early childhood often result from young
      childrens' lack of understanding of the dangers of certain situations and their
      physical inability to extricate themselves from potentially lethal circumstances.
      Two cases are reported to demonstrate an age-related susceptibility in the young
      to lethal head entrapment. Case 1: a 5-month-old girl smothered when she slipped
      down in her stroller, trapping her head beneath the frame and forcing her face
      into the soft material of the base. Case 2: a 14-month-old boy was hanged while
      exploring a filing cabinet when his head became caught between two lower drawers.
      Additional mental and physical characteristics that predispose young children and
      infants to lethal head entrapment include an inability to effectively problem
      solve once confronted with a hazardous situation, and relatively large heads and
      weak neck musculature. Because of these features lethal head entrapment
      represents a particular circumstance that may predispose to accidental asphyxial
      deaths in the very young. A combination of careful death scene and autopsy
      evaluations will be required to confirm the alleged circumstances of death in
      these cases, including mortuary re-enactments and assessment of the deceased
      infant's level of physical maturity and mobility.

PMID- 19573846
TI  - Crossbow injuries: a case report.
AB  - Despite the increasing popularity of crossbows in recreational hunting, injuries
      and deaths from crossbows are still relatively rare. In suicides, the body areas
      favoured are similar to those of gun users, namely the thorax and head. These
      deaths almost always occur in males. The case presented is that of a 49 year old
      male with a history of mental illness and suicidal attempts, who committed
      suicide with a crossbow. The weapon was discharged into the left thorax.
      Examination of crossbow injuries can be difficult due to their similarities with
      other incised wound patterns. As many victims may survive for some time after
      injury, removal of the bolt is possible. As well, removal of the bolt followed by
      advanced decomposition may alter the wound patterns. Careful examination of
      clothing, as well as entry wound reconstruction may give an indication to the
      weaponry used. Radiology is useful for detecting debris along the wound path, as
      well as position of the bolt when it is in situ. Finally, when dealing with cases
      of crossbow head injuries, consideration of both blood loss as well as diffuse
      axonal damage is important, both in non-fatal and fatal cases.

PMID- 19573847
TI  - The interaction of injury and disease in the elderly: a case report of fatal
      elder abuse.
AB  - We report a case of an elderly demented woman who died of a mitral rheumatic
      valvular disease in the context of multiple injuries and from elder abuse.
      History from police investigation indicated that the deceased was found collapsed
      on the floor in her bedroom for several days prior to death by her son who did
      not initiate medical care. Autopsy revealed a frail elderly woman with
      Alzheimer's disease and evidence of multiple healing sublethal blunt impact
      injuries of the face, mouth, neck, upper chest, and extremities. In addition,
      there was unwashed dirt encrusted skin, urine/fecal staining of skin and
      clothing, dirty overgrown toenails, and matting of the hair. This constellation
      of findings supports the medical diagnosis of elder abuse with neglect. However,
      the immediate cause of death was the left-sided congestive heart failure from
      mitral rheumatic valvular disease. Although the underlying cause of death was
      related to the chronic cardiac condition, the physical abuse and neglect was
      considered significant contributing factors to death, since physiologically the
      injuries and lack of medical treatment was thought to have hastened death by
      exacerbating the underlying heart disease. This case underscores the need for the
      forensic pathologist to consider contextual variables and sublethal injuries in
      cases were the causal interpretations benefit from a more holistic approach.
      Otherwise, cases like such as the one reported can go unnoticed and certified as
      a simple natural death.

PMID- 19573848
TI  - Accidental unilateral and incomplete strangulation injury in a patient while
      traveling on a bicycle.
AB  - Chunni (a piece of cloth worn around the neck by many Indian women) is a well
      recognized accidental ligature around the neck. We report a rare case of
      accidental strangulation with chunni where the patient was pillion rider on
      bicycle; in spite of very common of use of bicycle to best our knowledge this
      kind of injury has not been reported previously.

PMID- 19573849
TI  - Fatal transorbital head injury by bicycle brake handle.
AB  - Accidental transorbital head injuries are quite rare. Penetrating head injuries
      by blunt objects are possible when the site of penetration is through the orbit
      or the thin temporal bone. The present case is a rare case of transorbital
      penetrating head injury by a blunt object - bicycle brake handle. Minor external
      wounds may be misleading and fatal consequences may ensue if cerebral damage is
      missed on diagnosis. Proper antibiotic coverage to prevent meningitis and
      neurosurgical intervention can reduce mortality in such cases.

PMID- 19573850
TI  - Fatal cranial shot by blank cartridge gun: two suicide cases.
AB  - Blank firing pistols are generally considered to be harmless and these guns are
      not accepted as being firearms in most countries. Due to lack of legal
      regulations these guns are easily purchased by anyone aged over 18 years. Reports
      of serious injuries and even fatalities due to these guns are increasing in the
      literature. These guns when modified or even unmodified can cause serious and
      potentially fatal injuries. Without doing any changes to the barrel, using blank
      or tear gas cartridges, firing at contact range can cause penetration of gas into
      the body including bone originated from gun powder. We report two suicide cases
      shooting themselves at temporal region with a blank cartridge gun at contact
      range. There was no foreign body on radiological examination and there was no
      trajectory of a bullet inside the brain. In both cases the wound was at the right
      temporal region and there was defect at temporal bone. There was circular soot
      around this bone defect. The injury of the brain tissue was localized at the
      level of the defect but there was widespread subarachnoidal bleeding. We
      discussed the potential danger of these guns and stressed the need of legal
      regulations concerning these guns.

PMID- 19573851
TI  - Autopsy findings in a case of tuberous sclerosis.
AB  - Tuberous sclerosis is a neurocutaneous disorder with autosomal dominant
      inheritance. It is characterized by the triad of seizures, mental retardation,
      angiofibromas of the face though the triad is not always complete. We
      incidentally encountered a case of tuberous sclerosis in a case of hanging. He
      was an epileptic. Autopsy findings included unusual findings of myocardial and
      renal lipomata. He also had cortical thickening of bones, cortical tubers of
      brain, polycystic kidney disease.

PMID- 19573852
TI  - Traumatic degloving of male external genitalia.

PMID- 19573853
TI  - Cadaveric fungi: not yet an established forensic tool--authors' response.

PMID- 19573854
TI  - Preventing suicide in males: a suicide investigation in nine public health
      centers in Mie prefecture, Japan.

PMID- 19573855
TI  - "Suicidal poisoning in Southern India: gender differences"--authors' response.

PMID- 19573856
TI  - Dispersions, novel nanomaterial sensors and nanoconjugates based on carbon
      nanotubes.
AB  - Nanomaterials are structures with dimensions characteristically much below 100
      nm. The unique physical properties (e.g., conductivity, reactivity) have placed
      these nanomaterials in the forefront of emerging technologies. Significant
      enhancement of optical, mechanical, electrical, structural, and magnetic
      properties are commonly found through the use of novel nanomaterials. One of the
      most exciting classes of nanomaterials is represented by the carbon nanotubes.
      Carbon nanotubes, including single-wall carbon nanotubes, multi-wall carbon
      nanotubes, and concentric tubes have been shown to possess superior electronic,
      thermal, and mechanical properties to be attractive for a wide range of potential
      applications They sometimes bunch to form "ropes" and show great potential for
      use as highly sensitive electronic (bio)sensors due to the very small diameter,
      directly comparable to the size of single analyte molecules and that every single
      carbon atom is in direct contact with the environment, allowing optimal
      interaction with nearby molecules. Composite materials based on integration of
      carbon nanotubes and some other materials to possess properties of the individual
      components with a synergistic effect have gained growing interest. Materials for
      such purposes include conducting polymers, redox mediators and metal
      nanoparticles. These tubes provide the necessary building blocks for electronic
      circuits and afford new opportunities for chip miniaturization, which can
      dramatically improve the scaling prospects for the semiconductor technologies and
      the fabrication of devices, including field-effect transistors and sensors.
      Carbon nanotubes are one of the ideal materials for the preparation of
      nanoelectronic devices and nanosensors due to the unique electrical properties,
      outstanding electrocatalytic properties, high chemical stability and larger
      specific surface area of nanotubes. Carbon nanotubes are attractive material for
      supercapacitors due to their unique one-dimensional mesoporous structure, high
      specific surface area, low resistivity and good chemical stability. Nanoscaled
      composite materials based on carbon nanotubes have been broadly used due to their
      high chemical inertness, non-swelling effect, high purity and rigidity. The
      integration of carbon nanotubes with organics, biomaterials and metal
      nanoparticles has led to the development of new hybrid materials and sensors.
      Hybrid nanoscale materials are well established in various processes such as
      organic and inorganic compounds, nucleic acid detachment, protein separation, and
      immobilization of enzymes. Those nanostructures can be used as the building
      blocks for electronics and nanodevices because uniform organic and metal coatings
      with the small and monodisperse domain sizes are crucial to optimize nanoparticle
      conductivity and to detect changes in conductivity and absorption induced by
      analyte adsorption on these surfaces. The highly ordered assembly of zero
      dimensional and one-dimensional nanoparticles is not only necessary for making
      functional devices, but also presents an opportunity to develop novel collective
      properties.

PMID- 19573858
TI  - The need for comprehensive psychiatric perinatal care-the University of North
      Carolina at Chapel Hill, Department of Psychiatry, Center for Women's Mood
      Disorders launches the first dedicated Inpatient Program in the United States.

PMID- 19573861
TI  - Thought control strategies as mediators of trauma symptoms in young women with
      histories of child sexual abuse.
AB  - The current retrospective study examined thought control strategies, or cognitive
      techniques individuals use to deal with unpleasant thoughts following stressful
      events, as potential mediators of adjustment in young women with histories of
      child sexual abuse (CSA). In a sample of 76 undergraduate women who self-reported
      on abuse experiences, thought control strategies, and current trauma symptoms,
      several key findings emerged: (i) Greater severity of the CSA event was
      associated with greater reported use of worry and punishment strategies and less
      use of social control strategies; (ii) Increased use of worry and punishment
      strategies following the CSA event was associated with greater levels of trauma
      symptoms, while increased use of social control strategies following the CSA
      event was associated with lower levels of trauma symptoms; and (iii) Worry,
      punishment, and social control strategies served as mediators between CSA
      severity and trauma symptoms. The results suggest that thought control
      strategies, specifically increased worry and punishment, and decreased social
      control, play a vital role in understanding adjustment after CSA. Future research
      should examine the roles of these cognitive control strategies as possible
      avenues of intervention following CSA.

PMID- 19573859
TI  - Bilateral abnormalities of optic nerve size and eye shape in unilateral
      amblyopia.
AB  - PURPOSE: To evaluate the optic nerve (ON) size and globe shape in amblyopic eyes
      using high-resolution magnetic resonance imaging (MRI) and to compare these
      values with those of the sound fellow eye and of normal control eyes. DESIGN:
      Prospective case-control study. METHODS: Thirty-four amblyopic patients and 60
      normal control patients were evaluated using surface coil MRI. Retrobulbar ON
      cross-section, maximum globe cross-section, globe noncircularity (globe major
      axis/minor axis), axial length (AL), and the ratio of AL to ON (AL/ON) were
      measured. RESULTS: Corrected logarithm of the minimum angle of resolution acuity
      of all 34 amblyopic eyes averaged 0.43 +/- 0.30. The mean retrobulbar ON cross
      section was 9.7 +/- 2.4 mm(2), 9.5 +/- 2.3 mm(2), and 10.7 +/- 2.6 mm(2) for
      amblyopic, fellow, and normal ONs, respectively. Although amblyopic and fellow
      ONs had similar cross-sections, both were significantly (P = .02) subnormal.
      AL/ON was 2.7 +/- 1.2 mm(-1), 2.7 +/- 1.0 mm(-1), and 2.3 +/- 0.5 mm(-1),
      respectively. Although AL/ON significantly exceeded normal in amblyopic eyes (P =
      .01), there was no significant difference between amblyopic and fellow eyes.
      Globe noncircularity of amblyopic eyes (1.17 +/- 0.07; P = .002) and fellow eyes
      (1.15 +/- 0.04; P < .001) was significantly greater than that of control eyes
      (1.11 +/- 0.04), but amblyopic and fellow eyes did not differ significantly.
      CONCLUSIONS: Unilateral amblyopia is associated with bilaterally, but also with
      subclinically hypoplastic ONs, greater than normal AL/ON, and abnormally
      noncircular globe cross-section. These factors evidently do not determine which
      of the 2 eyes will become amblyopic. Reduced circularity of amblyopic and fellow
      eyes may reflect optical causes of amblyopia or bilateral dysregulation of globe
      shape secondary to amblyopia.

PMID- 19573860
TI  - Fundus autofluorescence in type 2 idiopathic macular telangiectasia: correlation
      with optical coherence tomography and microperimetry.
AB  - PURPOSE: To use multiple imaging methods to investigate patients with type 2
      idiopathic macular telangiectasia (IMT) at different disease severity stages so
      as to characterize and categorize disease progression through the full spectrum
      of disease phenotypes. DESIGN: Observational case series. METHODS: Twelve
      patients with type 2 IMT (22 eyes) examined with fundus photography, angiography,
      optical coherence tomography imaging, fundus autofluorescence (FAF), and
      microperimetry testing in an institutional setting. RESULTS: Eyes examined by
      multiple imaging methods were classified into 5 proposed categories (0 through
      4): category 0 (fellow) eyes had normal results on all imaging methods. Category
      1 eyes had increased foveal autofluorescence on FAF imaging as the only imaging
      abnormality. Category 2 eyes had increased foveal autofluorescence together with
      funduscopic and angiographic features typical of type 2 IMT. Category 3 eyes had
      additional evidence of foveal atrophy on optical coherence tomography, and
      category 4 eyes had all the above features plus clinically evident pigment
      clumping. FAF signal increased in intensity in the foveal region from category 0
      through category 3, whereas category 4 eyes demonstrated a mixed pattern of
      increased and decreased FAF signal. CONCLUSIONS: The findings here outline a
      sequence of progressive changes seen with multiple imaging methods in advancing
      stages of disease. Increase in foveal autofluorescence is an early anatomic
      change in type 2 IMT that may precede typical clinical and angiographic changes.
      Loss of macular pigment density in the fovea and a changing composition of
      fluorophores in the retinal pigment epithelium may underlie these changes on FAF
      in the fundus.

PMID- 19573862
TI  - A threshold level of TLR9 mRNA predicts cellular responsiveness to CpG-ODN in
      haematological and non-haematological tumour cell lines.
AB  - The human toll like receptor 9 (TLR9) detects differences between microbial and
      host DNA, based on unmethylated deoxycytidyl deoxyguanosine dinucleotide (CpG)
      motifs, leading to activation of both innate and adaptive immune mechanisms. The
      synthetic TLR9 agonist, CpG-ODN, can substitute for microbial DNA in these
      responses, and is in clinical trials as an immunomodulatory agent in diseases as
      diverse as infections, cancer and allergic disorders. Human TLR9 is expressed on
      cells of haematopoietic origin (principally plasmacytoid dendritic cells and B
      cells), but has also been described as being expressed on a number of other cell
      types. In order to clarify the expression and function of TLR9 in a range of
      cells of both haematopoietic and non-haematopoietic origin, we investigated the
      level of expression of TLR9 mRNA, and the ability of the cells to respond to CpG
      ODN by upregulation of cell surface markers, cytokine production, cellular
      proliferation and activation of NFkappaB. Our data show that the cellular
      response to CpG-ODN depended on a threshold level of expression of TLR9. TLR9 was
      widely expressed amongst B cell tumours (with the exception of myeloma cell
      lines), but we did not find either threshold levels of expression of TLR9 or
      responses to CpG-ODN in several myeloma or myeloid tumour cell lines or any non
      haematological tumour cell lines tested in our study. TLR9-positive cells varied
      significantly in their responses to CpG-ODN, and the level of TLR9 expression
      beyond the threshold did not correlate with the magnitude of the response to CpG
      ODN. Finally, CpG-ODN induced NFkappaB activation and increased cellular
      proliferation in Hek293 cells that had been stably transfected with hTLR9, but
      did not affect the expression of surface markers or synthesis of IL-6, IL-10 or
      TNF-alpha. Thus both haematological and non-haematological cells expressing
      appropriate levels of TLR9 respond to CpG-ODN, but the nature of the TLR9
      mediated response is dependent on cell type.

PMID- 19573863
TI  - Easy on the mind, easy on the wrongdoer: discrepantly fluent violations are
      deemed less morally wrong.
AB  - The present experiment tested the hypothesis that discrepancies in processing
      fluency influence the perceived wrongness of moral violations. Participants were
      presented with numerous moral violations in easy or difficult to read font. For
      some violations experienced perceptual fluency was consistent with the fluency
      associated with previous violations, whereas for others it was more fluent or
      more disfluent. Results show that, across multiple vignettes, participants rated
      moral violations that were processed with discrepant fluency as less morally
      wrong than those processed with discrepant disfluency. The current work
      highlights the importance of metacognitive experiences in moral judgment and
      contributes to the emerging literature on the role of experiential factors in
      moral judgment.

PMID- 19573864
TI  - Successful hemostasis for Dieulafoy's lesion with a large protruding vessel in
      the stomach: clipping of the artery under the mucosa (with video).

PMID- 19573865
TI  - Disseminated histoplasmosis with colonic ulcers in a patient receiving
      infliximab.

PMID- 19573866
TI  - Large-balloon technique for one-step endoscopic biliary stenting in patients with
      an inaccessible major papilla owing to difficult duodenal stricture (with video).
AB  - BACKGROUND: Marked duodenal stenosis makes endoscopic biliary stenting (EBS)
      impossible, although it is the most common method for treating obstructive
      jaundice in patients with benign or malignant biliary strictures. Large-balloon
      dilation can be used to enable endoscope passage in the GI tract. OBJECTIVE: We
      describe 4 cases of successful EBS combined with the use of a large balloon for
      the treatment of difficult duodenal strictures in patients with benign and
      malignant biliary strictures. DESIGN: A retrospective case series. SETTING: Two
      tertiary referral centers. PATIENTS: Four patients: 1 with hilar carcinoma, 1
      with gallbladder carcinoma, and 2 with chronic pancreatitis. INTERVENTIONS: After
      duodenal dilation, the slightly deflated balloon was pushed with the endoscope
      into the major papilla through the duodenal stricture (pushing method used in 2
      patients). In the cases in which the major papilla was not accessible with the
      pushing method, a large dilation balloon was deflated completely after dilation,
      advanced beyond the stricture into the third portion of the duodenum, and
      reinflated to the maximum size. Pulling the dilation balloon catheter into the
      working channel while hooking the inflated balloon as the anchor at the anal side
      of the duodenal stricture, the endoscope was straightened to advance to the major
      papilla (hooking method used in 2 patients). MAIN OUTCOME MEASUREMENT: Successful
      EBS. RESULTS: Reaching the major papilla and EBS was accomplished in all 4
      patients. LIMITATION: Small number of cases. CONCLUSIONS: Use of large-balloon
      dilation can contribute to successful ERCP in patients with difficult duodenal
      strictures.

PMID- 19573867
TI  - Clinical role of frequency-doubled double-pulsed yttrium aluminum garnet laser
      technology for removing difficult bile duct stones (with videos).
AB  - BACKGROUND: Very few clinical trials have reported on the success rate of
      frequency-doubled double-pulse yttrium aluminum garnet (YAG) laser (FREDDY)
      technology for removal of difficult bile duct stones. OBJECTIVE: Our purpose was
      to evaluate the role of FREDDY technology for removing difficult bile duct
      stones. DESIGN: Nonrandomized, retrospective study. SETTING: Academic medical
      center. PATIENTS: Fifty-two patients with difficult bile duct stones were treated
      via the transpapillary route by using a FREDDY system. The inclusion criteria
      were impacted or large common bile duct stones (>15 mm, mean 23.5 mm, range 15-35
      mm, mean number of stones 1.7, range 1-4). Laser lithotripsy was performed with
      cholangioscopy guidance in 7 patients and fluoroscopic guidance alone in 45
      patients. MAIN OUTCOME MEASUREMENTS: The success rate of complete stone removal
      and the complication rate related to the procedure. RESULTS: Of the 52 patients
      treated via the transpapillary route, complete stone removal was achieved in 48
      patients (92.3%). The complete removal of stones required a mean of 1.4 (range 1
      2) endoscopic sessions. The rate of complications related to laser lithotripsy
      was 23.0% (acute pancreatitis, 3 cases; transient hemobilia, 8 cases; acute
      cholangitis, 1 case). LIMITATIONS: Nonrandomized, retrospective design.
      CONCLUSION: Laser lithotripsy by using the FREDDY system seems safe and effective
      and allows "blind" fragmentation of bile duct stones under fluoroscopic guidance
      only.

PMID- 19573868
TI  - Comparative evaluation of nasoenteral feeding and jejunostomy feeding in acute
      corrosive injury: a retrospective analysis.
AB  - BACKGROUND: Nutritional support in corrosive injury patients is traditionally
      achieved through total parenteral nutrition (TPN) or jejunostomy feeding (JF).
      There are no reports of nasoenteral tube feeding in patients with corrosive
      ingestion. OBJECTIVE: We report our experience with nasoenteral tube feeding
      (NETF) and compare the outcome of these patients with those undergoing JF.
      SETTING: Tertiary medical center in North India. DESIGN AND INTERVENTION: The
      records of 53 and 43 patients with severe acute corrosive injury who underwent
      NETF and JF, respectively, were reviewed. All had received a 50-kcal/kg, 2-g/kg
      protein homogenized liquid diet for 8 weeks. A contrast study was performed at 8
      weeks, and body weight and serum albumin levels were recorded at hospitalization
      and at 8 weeks. MAIN OUTCOME MEASUREMENTS: Change in weight and serum albumin at
      8 weeks and stricture development rate. RESULTS: Strictures developed in 41
      (80.39%) and 36 (83.72%) patients in the NETF and JF groups, respectively.
      Development of esophageal stricture (P = .71) and gastric stenosis (P = .89) was
      comparable in the 2 groups. No significant changes in serum albumin and weight
      were noted at 8 weeks in either group. The complication rate was lower in the
      NETF group compared with the JF group. Although all of the patients in the NETF
      group had a patent lumen, 5 in the JF group had total obstruction precluding
      endoscopic intervention. LIMITATIONS: Retrospective study design. CONCLUSION:
      NETF is as effective as JF in maintaining nutrition in patients with severe
      corrosive injury. The stricture development rate is similar, but nasoenteral tube
      placement provides a lumen for dilatation should a tight stricture develop.

PMID- 19573869
TI  - A randomized comparison of electrocautery incision with Savary bougienage for
      relief of anastomotic gastroesophageal strictures.
AB  - BACKGROUND: Benign gastroesophageal anastomotic strictures are common and often
      refractory to treatment. Various endoscopic dilation techniques have been
      reported, but none of these methods has been proven to be superior. OBJECTIVE:
      Comparison of the efficacy and safety of dilation of previously untreated
      anastomotic strictures by using electrocautery incision (EI) and Savary
      bougienage (SB). DESIGN: Randomized, prospective study. SETTING: Multicenter
      study. PATIENTS: Sixty-two patients with an anastomotic stricture after
      esophagogastrostomy and dysphagia Atkinson grades II to IV were included.
      INTERVENTIONS: Patients were treated with EI or SB. MAIN OUTCOME MEASUREMENTS:
      Objective and subjective results were compared with baseline and 1, 3, and 6
      months after the first treatment. Complications of both treatments were noted.
      Primary endpoints after 6 months were the mean number of dilation sessions and
      success rate (percentage of patients with < or =5 dilations in 6 months). Study
      participation ended after 6 months or if dysphagia grades II to IV recurred
      despite 5 treatment sessions. RESULTS: No complications occurred with both
      treatments. There was no significant difference between the EI and SB groups in
      the mean number of dilations (2.9; 95% CI, 2.7-4.1 vs 3.3; 95% CI, 2.3-3.6l; P =
      .46) or the success rate (80.6% vs 67.7%, P = .26 and 96.2% vs 80.8%, P = .19).
      LIMITATIONS: In a small study with negative primary endpoints, secondary
      endpoints and subgroup analyses are hypothesis generating only. CONCLUSIONS: This
      prospective trial demonstrated that EI of gastroesophageal anastomotic strictures
      is a safe therapy and equivalent to SB as a primary therapy. EI can be used as an
      alternative or additional therapy to SB. (Registered with Current Controlled
      Trials, Ltd, registration number ISRCTN81239664.).

PMID- 19573870
TI  - The naming of new species in hominin evolution: A radical proposal--A temporary
      cessation in assigning new names.
AB  - The species problem is one of the most complex and enduring problems plaguing
      evolutionary biology in general and human paleontology in particular. In the past
      50 years, conceptions of species have diverged and speciated analogous to the
      present, largely accepted view of the hominin phylogeny. Conventional wisdom
      supports a "bushy" hominin phylogeny. However, chaos reigns because there is no
      agreed-upon methodology used to delimit species taxa in paleontology. This
      dispute is complicated by the ever-present intraspecific and interspecific
      morphological variation, which is itself exacerbated by other types of variation,
      including behavioral, ecological, geographical and temporal. When two or more of
      these forms of variation are used to delimit "new" extant or fossil species, any
      decision arrived at might be construed as arbitrary. This paper proposes that
      temporary cessation in assigning new names should be considered based on several
      critical problems: (1) the explosion of conceptions of a "species" arising from
      disagreements regarding species definitions, (2) differing interpretations of
      population variation, which lead to difficulty in interpreting hybridization in
      nature, leading in turn to the underestimation or overestimation of species, (3)
      the problem of modes of speciation being confounded with criteria used to
      distinguish among species, e.g., punctuated equilibrium posits high-speciation
      rates, and (4) the most common of all human traits, vanity.

PMID- 19573871
TI  - Evaluation of intramedullary rib splints for less-invasive stabilisation of rib
      fractures.
AB  - BACKGROUND: Intramedullary fixation of rib fractures with generic Kirschner wires
      has been practiced for over 50 years. However, this technique has not been
      advanced to address reported complications of wire migration and cut-out. This
      biomechanical study evaluated a novel rib splint designed to replicate the less
      invasive fixation approach of Kirschner wires while mitigating their associated
      complications. METHODS: The durability, strength, and failure mode of rib
      fracture fixation with intramedullary rib splints were evaluated in 27 cadaveric
      ribs. First, intact ribs were loaded to failure to determine their strength and
      to induce realistic rib fractures. Subsequently, fractures were stabilised with a
      novel rib splint made of titanium alloy with a rectangular cross-section that was
      secured with a locking screw. All fixation constructs were dynamically loaded to
      360,000 cycles at five times the respiratory load magnitude to determine their
      durability. Finally, constructs were loaded to failure to determine their
      residual strength and failure modes. RESULTS: Native ribs had a strength of 9.7+/
      5.0 N m, with a range of 3.5-19.6 N m. Fracture fixation with rib splints was
      uneventful. All 27 splint constructs sustained dynamic loading without fixation
      failure, implant migration or implant cut-out. Dynamic loading caused no
      significant decrease in construct stiffness (p=0.85) and construct subsidence
      remained on average below 0.5 mm. The residual strength of splint constructs
      after dynamic loading was 1.1+/-0.24 N m. Constructs failed by splint bending in
      44% of specimens and by developing fracture lines along the superior and inferior
      cortices in 56% of specimens. Regardless of the failure mode, all rib splint
      constructs recoiled elastically after failure and retained functional reduction
      and fixation. No construct exhibited implant cut-out or migration through the
      lateral cortex. CONCLUSIONS: Rib splints can provide sufficient stability to
      support respiratory loading throughout the healing phase, but they cannot restore
      the full strength of native ribs. Most importantly, rib splints mitigated the
      complications reported for rib fracture fixation with generic Kirschner wires,
      namely implant cut-out and migration through the lateral cortex. Therefore, rib
      splints may provide an advanced alternative to the original Kirschner wire
      technique for less-invasive fixation of rib fractures.

PMID- 19573872
TI  - Registered nurses' and nurse assistants' lived experience of troubled conscience
      in their work in elderly care--a phenomenological hermeneutic study.
AB  - BACKGROUND: In elderly care registered nurses (RNs) and nurse assistants (NAs)
      face ethical challenges which may trouble their conscience. OBJECTIVE: This study
      aimed to illuminate meanings of RNs' and NAs' lived experience of troubled
      conscience in their work in municipal residential elderly care. DESIGN:
      Interviews with six RNs and six NAs were interpreted separately using a
      phenomenological hermeneutic method. SETTINGS: Data was collected in 2005 among
      RNs and NAs working in special types of housings for the elderly in a
      municipality in Sweden. PARTICIPANTS: The RNs and NAs were selected for
      participation had previously participated in a questionnaire study and their
      ratings in the questionnaire study constituted the selection criteria for the
      interview study. RESULTS: The RNs' lived experience of troubled conscience was
      formulated in two themes. The first theme is 'being trapped in powerlessness'
      which includes three sub-themes: being restrained by others' omission, being
      trapped in ethically demanding situations and failing to live up to others'
      expectations. The second theme is 'being inadequate' which includes two sub
      themes: lacking courage to maintain one's opinion and feeling incompetent. The
      NAs' lived experience of troubled conscience was formulated in the two themes.
      The first is 'being hindered by pre-determined conditions' which includes two sub
      themes: suffering from lack of focus in one's work and being restrained by the
      organisation. The second theme is 'being inadequate' which includes two sub
      themes: lacking the courage to object and being negligent. CONCLUSIONS: The RNs'
      lived experience of troubled conscience were feelings of being trapped in a state
      of powerlessness, caught in a struggle between responsibility and authority and a
      sense of inadequacy fuelled by feelings of incompetence, a lack of courage and a
      fear of revealing themselves and endangering residents' well-being. The NAs'
      lived experience of troubled conscience was feelings of being hindered by pre
      determined conditions, facing a fragmented work situation hovering between norms
      and rules and convictions of their conscience. To not endangering the atmosphere
      in the work-team they are submissive to the norms of their co-workers. They felt
      inadequate as they should be model care providers. The findings were interpreted
      in the light of Fromm's authoritarian and humanistic conscience.

PMID- 19573873
TI  - Co-isolation of deoxynivalenol and zearalenone with sol-gel immunoaffinity
      columns for their determination in wheat and wheat products.
AB  - The paper describes a sample clean-up method for the co-isolation of
      deoxynivalenol (DON) and zearalenone (ZON), two mycotoxins naturally co-occurring
      in wheat. The method is based on immunoaffinity columns prepared by co
      immobilising anti-DON and anti-ZON antibodies in a porous sol-gel glass. The main
      task in developing the method consisted in finding a loading medium allowing
      retention of both analytes as well as a common elution medium for the
      dissociation of both antigen-antibody complexes formed. This can be achieved by
      co-extracting DON and ZON with ACN-water (60:40, v/v), reducing the acetonitril
      concentration to 2.5% before loading an aliquot of the diluted sample extract
      onto the DON/ZON column. The columns are washed with 5 ml of MeOH-water (10:90,
      v/v) before DON and ZON are co-eluted with 4 ml of ACN-water (50:50, v/v).
      Concentrations of DON and ZON are determined with HPLC-UV and HPLC-fluorescence
      detection, respectively. The sample clean-up method was shown to be applicable to
      wheat and wheat products, e.g., cornflakes, milk wheat mash and rusk. Spiking
      experiments (spike level 500 microg DON/kg and 50 microg ZON/kg) resulted in
      recovery rates from 82% to 111%.

PMID- 19573874
TI  - Determination of isoelectric points of metals and metallic alloys by adhesion of
      latex particles.
AB  - A set-up and a method were developed to determine the isoelectric point of metals
      and metallic alloys samples (stainless steels, inconel, zircaloy, aluminum and
      dural) by measuring the adhesion rate of negative latex particles. The
      concentration of polystyrene spheres with surface carboxylate groups (initially
      0.5-1 mg L(-1)) in contact with metallic samples was measured as a function of pH
      and time by turbidimetry. The simulation of measurements by a model predicting
      the sticking coefficient based on DLVO theory was used for the determination of
      the isoelectric point from experimental results. It was found that the
      isoelectric points of aluminum (8.7) and dural (9.1), treated by boiling water,
      are close to those of hydrated aluminum oxides powders. For stainless steels,
      inconel and zircaloy, the values of isoelectric points were found to be between
      2.4 and 3.0, far below the isoelectric points measured for metallic oxides
      constituting the alloy surface layer. This difference was explained by two
      different charging mechanisms: (1) deprotonation of hydroxyl groups on the
      surface of the metal oxide in suspension or as a thick layer, (2) adsorption of
      hydroxide ions on a metal surface covered by a thin oxide layer, as observed on
      hydrophobic surfaces.

PMID- 19573875
TI  - Evaluation of interfacial equilibrium constants from surface potential data:
      silver chloride aqueous interface.
AB  - A single crystal silver chloride electrode (SCr-AgCl) was used to measure the
      inner surface potential (Psi(0)) at the silver chloride aqueous electrolyte
      interface as a function of activity of Cl(-) ions as determined by the Ag/AgCl
      electrode. Absolute values of the surface potential were calculated from
      electrode potentials of SCr-AgCl using the value of point of zero charge
      (pCl(pzc)=5.2) as the value of point of zero potential. Measurements were
      performed in potassium nitrate aqueous solutions, as well as in the presence of
      Li, Na, Cs, Mg, and La nitrates. The Psi(0) (pCl) function was found to be linear
      within the experimental error and practically the same for all the examined
      electrolytes and almost independent of ionic strength. The reduction of the slope
      with respect to the Nernst equation, expressed by the alpha coefficient, was
      (0.88+/-0.01) at I(c)=10(-1) mol dm(-3), (0.87+/-0.01) at I(c)=10(-2) mol dm(-3),
      and (0.84+/-0.01) at I(c)=10(-3) mol dm(-3). The results were successfully
      interpreted by employing the surface complexation model developed originally for
      metal oxides and adapted for silver chloride. The standard ("intrinsic")
      equilibrium constants for the binding of chloride (K(o)(n)) and silver ions
      (K(o)(p)) on the corresponding sites at the silver chloride surface were
      evaluated as lg K(o)(n)=2.67+/-0.05; lg K(o)(p)=2.07+/-0.05. Counterion surface
      association equilibrium constants were also obtained as lg K(o)(NO3(-))=lg
      K(o)(K+)=274+/-0.05.

PMID- 19573876
TI  - Social defeat stress produces prolonged alterations in acoustic startle and body
      weight gain in male Long Evans rats.
AB  - Individuals exposed to psychological stressors may experience a long-term
      resetting of behavioral and neuroendocrine aspects of their "stress response" so
      that they either hyper or hypo-respond to subsequent stressors. These effects of
      psychological or traumatic stressors may be mimicked in rats using the resident
      intruder model of social defeat. The social defeat model has been characterized
      to model aspects of the physiology and behavior associated with anxiety and
      depression. The objective of this study was to determine if behaviors elicited
      following repeated social defeat can also reflect aspects of ethologically
      relevant stresses associated with existing post traumatic stress disorder (PTSD)
      models. Socially defeated rats displayed weight loss and an enhanced and
      prolonged response to acoustic startle which was displayed for up to 10days
      following repeated social defeat. These data indicate that the severe stress of
      social defeat can produce physiologic and behavioral outcomes which may reflect
      aspects of traumatic psychosocial stress.

PMID- 19573877
TI  - Recanalization of the MCA should play an important role in dramatic recovery
      after t-PA therapy in patients with ICA occlusion.
AB  - BACKGROUND AND PURPOSE: The intravenous t-PA thrombolysis is not thought to be
      effective in most patients with internal carotid artery (ICA) occlusion. However,
      we have sometimes observed dramatic recovery in patients with ICA occlusion after
      t-PA therapy. The aim of the present study was to investigate the mechanism of
      dramatic recovery in such patients. METHODS: Consecutive ICA occlusion patients
      treated with t-PA were prospectively studied. MRI, including MRA, was performed
      before and within 1 h and 24 h after t-PA thrombolysis. Patients were divided
      into 2 groups: dramatic recovery (D group) and non-dramatic recovery (ND group).
      RESULTS: The subjects consisted of 21 consecutive stroke patients (14 males; mean
      age, 76.5+/-8.4 years). Six (28.6%) patients (D group) had dramatic improvement
      and 15 (71.4%) patients (ND group) did not. The frequency of partial or complete
      recanalization within 1 h and 24 h after t-PA infusion was 14.3% and 50.0% for
      the ICA, 9.5% and 40.0% for the MCA, and 23.8% and 65.0% for the ICA or MCA,
      respectively. There was no difference in the frequency of ICA recanalization 24 h
      after t-PA infusion between the 2 groups (66.7% for D group vs. 42.9% for ND
      group, P=0.629); however, MCA recanalization was more frequent in the D group
      than in the ND group (100.0% vs. 14.3%, P=0.0004). CONCLUSION: Recanalization of
      the MCA, which provides collateral flow, appears to play an important role in
      dramatic recovery after t-PA therapy in patients with ICA occlusion.

PMID- 19573878
TI  - Ethnic South Asian ischaemic stroke patients have a higher prevalence of a family
      history of vascular disease compared to age, gender and diabetes-matched ethnic
      Chinese subjects.
AB  - Family history is a known non-modifiable risk factor of stroke. We aimed to
      compare the frequency of a family history of vascular disease between ethnic
      South Asian and Chinese stroke patients. We studied consecutive ethnic South
      Asian and Chinese ischaemic stroke patients matched for age, gender and presence
      of diabetes. Among the 152 matched pairs, ethnic South Asian ischaemic stroke
      patients had a higher frequency of vascular family history (IHD OR 3.465 p<0.001;
      CVD OR 1.754 p=0.059; and either IHD or CVD OR 2.169 p=0.003) compared to matched
      ethnic Chinese patients, independent of past IHD history and stroke subtype. In
      the ethnic South Asian cohort, patients < or = 60 years old had a higher
      frequency of a family history of IHD (37% vs 13%, p<0.001), CVD (34% vs 15%,
      p=0.005) and either IHD or CVD (52% vs 25%, p<0.001) compared to those >60 years.
      Family history of vascular disease is common among ethnic South Asian ischaemic
      stroke patients, particularly among those < or = 60 years old. We postulate that
      the higher frequency of a vascular family history among ethnic South Asians
      compared to ethnic Chinese may be explained by genetic, environmental and
      lifestyle influences, or interactions between these factors.

PMID- 19573879
TI  - Aphasic and visual aura with increased vasogenic leakage: an atypical migrainosus
      status.
AB  - The pathogenesis of migraine with aura has not been fully established yet. The
      release of vasoactive substances and intracranial extracerebral blood vessel
      vasodilatation are probably related to stimulation of meningeal blood vessels
      through trigeminal afferents. Here, we report a 67 year old woman developing
      migraine with aphasia and right hemianopsia, lasting 4 days in duration. After
      spontaneous recovery, she experienced the same symptoms without migraine lasting
      for 15 h. MRI, performed during this last episode, revealed increased perfusion
      and leakage of contrast into subarachnoid space. In migraine with prolonged aura
      hyperperfusion with vasogenic edema might explain cortical function impairment
      and contribute to neurological deficits.

PMID- 19573880
TI  - [Mitroaortic endocarditis complicated with fistulated mitral abscess].

PMID- 19573881
TI  - [Tophaceous gout with chronic and deforming arthropathy].

PMID- 19573882
TI  - [Mycotic aneurysm of infrarenal abdominal aorta due to Coxiella burnetii].

PMID- 19573884
TI  - Preliminary report: No association between TCF7L2 rs7903146 and euglycemic-clamp
      derived insulin sensitivity in a mixed-age cohort.
AB  - There are conflicting reports about the significance of TCF7L2 single nucleotide
      polymorphism rs7903146, a single nucleotide polymorphism found to be associated
      with type 2 diabetes mellitus in several genomewide association studies, and
      insulin sensitivity. The association of rs7903146 and euglycemic-clamp-derived
      insulin sensitivity was tested in a cohort of children and their parents. Four
      hundred seventy whites (from 226 families) and 89 African Americans (from 48
      families) were included in the analysis. No significant associations were seen
      between rs7903146 and insulin sensitivity. Adjusted genotype means were
      consistent across races and generational subgroups.

PMID- 19573883
TI  - Effects of endurance training on cardiorespiratory fitness and substrate
      partitioning in postmenopausal women.
AB  - We examined the effect of endurance training on energy substrate partitioning
      during rest and exercise in postmenopausal women. Ten healthy sedentary (55 +/- 1
      years old) subjects completed 12 weeks of endurance exercise training on a cycle
      ergometer (5 d/wk, 1 h/d, 65% peak oxygen consumption [Vo(2)peak]). Whole-body
      energy substrate oxidation was determined by indirect calorimetry during 90
      minutes of rest and 60 minutes of cycle ergometer exercise. Subjects were studied
      at 65% Vo(2)peak before training and after training at the same absolute exercise
      intensity (same absolute workload as 65% of pretraining Vo(2)peak) and same
      relative exercise intensity (65% of posttraining Vo(2)peak). After training,
      Vo(2)peak increased by 16.3% +/- 3.9% and resting heart rate decreased by 4 beats
      per minute (P < .05). During exercise at same absolute intensity, mean arterial
      pressure decreased by 8 mm Hg (P < .05), heart rate decreased by 19 beats per
      minute (P < .05), energy derived from carbohydrate decreased by 9.6%, and the
      energy derived from lipid increased by 9.2% (P < .05). Lactate concentration was
      lower at the same absolute and relative exercise intensities (P < .05). Changes
      in substrate partitioning during exercise were accomplished without changes in
      dietary composition, body weight, or body composition. We conclude that endurance
      training in healthy postmenopausal women who remain in energy balance results in
      many of the classic cardiopulmonary training effects, decreases the reliance on
      carbohydrate, and increases lipid oxidation during a given submaximal exercise
      task without a reduction in body weight.

PMID- 19573885
TI  - Vascular endothelial growth factor during hypoglycemia in patients with type 1
      diabetes mellitus: relation to cognitive function and renin-angiotensin system
      activity.
AB  - In healthy adults, levels of vascular endothelial growth factor (VEGF) increase
      in response to mild hypoglycemia. VEGF is implicated in glucose transport over
      the blood-brain barrier, and the increase during hypoglycemia has been positively
      correlated with preservation of cognitive function during hypoglycemia. High
      activity in the renin-angiotensin system (RAS) is associated with an increased
      risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin
      angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We
      studied the impact of mild hypoglycemia on plasma VEGF in patients with type 1
      diabetes mellitus and high or low RAS activity and analyzed associations between
      VEGF levels and cognitive function during hypoglycemia. Eighteen patients with
      type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a
      single-blinded, placebo-controlled, crossover study with either mild hypoglycemia
      or stable glycemia. Cognitive function was assessed by the California Cognitive
      Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2
      (0.3) mmol/L. During the control study, plasma VEGF did not change. During
      hypoglycemia, plasma VEGF increased from 39 to 58 pg/L in the high-RAS group (P =
      .004) and from 76 to 109 pg/L in the low-RAS group (P = .01), with no difference
      between RAS groups (P = .9). A weak association between reduced preservation of
      cognitive function during hypoglycemia and low VEGF response was observed. Plasma
      VEGF levels increase during mild, short-term hypoglycemia in patients with type 1
      diabetes mellitus. The VEGF response is not dependent on RAS activity and only
      weakly associated with preservation of cognitive function during hypoglycemia.
      Thus, the previously described association between low RAS activity and better
      cognitive performance during hypoglycemia does not seem to be mediated by VEGF.

PMID- 19573886
TI  - FLOTAC: a promising technique for detecting helminth eggs in human faeces.
AB  - There is a tendency to neglect diagnostic issues in the era of 'preventive
      chemotherapy' in human helminthiases. However, accurate diagnosis cannot be
      overemphasized for adequate patient management and monitoring of community-based
      control programmes. Implicit is a diagnostic dilemma: the more effective
      interventions are in reducing helminth egg excretion, the less sensitive direct
      parasitological tests become. Here, experiences gained thus far with the FLOTAC
      technique for diagnosing common soil-transmitted helminth infections are
      summarized. A single FLOTAC has higher sensitivity than multiple Kato-Katz thick
      smears in detecting low-intensity infections. Further validation of the FLOTAC
      technique in different epidemiological settings is warranted, including diagnosis
      of intestinal schistosomiasis and food-borne trematodiases.

PMID- 19573889
TI  - Comment on: Influence of temperature and rainfall on the evolution of cholera
      epidemics in Lusaka, Zambia, 2003-2006: analysis of a time series.

PMID- 19573890
TI  - The role of the PI3K-Akt signal transduction pathway in Autographa californica
      multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells.
AB  - Many viruses activate the phosphatidylinositol 3-kinase (PI3K)-Akt signaling
      pathway, thereby modulating diverse downstream signaling pathways associated with
      antiapoptosis, proliferation, cell cycling, protein synthesis and glucose
      metabolism, in order to augment their replication. To date, the role of the PI3K
      Akt pathway in Baculovirus replication has not been defined. In the present
      study, we demonstrate that infection of Sf9 cells with Autographa californica
      multiple nucleopolyhedrovirus (AcMNPV) elevated cellular Akt phosphorylation at 1
      h post-infection. The maximum Akt phosphorylation occurred at 6 h post-infection
      and remained unchanged until 18 h post-infection. The PI3K-speci fi c inhibitor,
      LY294002, suppressed Akt phosphorylation in a dose-dependent manner, suggesting
      that AcMNPV-induced Akt phosphorylation is PI3K-dependent. The inhibition of PI3K
      Akt activation by LY294002 significantly reduced the viral yield, including a
      reduction in budded viruses and occlusion bodies. The virus production was
      reduced only when the inhibitor was added within 24 h of infection, implying that
      activation of PI3K occurred early in infection. Correspondingly, both viral DNA
      replication and late (VP39) and very late (POLH) viral protein expression were
      impaired by LY294002 treatment; LY294002 had no effect on immediate-early (IE1)
      and early-late (GP64) protein expression. These results demonstrate that the PI3K
      Akt pathway is required for efficient Baculovirus replication.

PMID- 19573891
TI  - Removal of arsenic from water: effects of competing anions on As(III) removal in
      KMnO4-Fe(II) process.
AB  - Effects of sulfate, phosphate, silicate and humic acid (HA) on the removal of
      As(III) in the KMnO(4)-Fe(II) process were investigated in the pH range of 4-9
      with permanganate and ferrous sulfate applied at selected dosage. Sulfate
      decreased the removal of arsenic by 6.5-36.0% at pH 6-9 and the decrease in
      adsorption did not increase with increasing concentration of sulfate from 50 to
      100mg/L. In the presence of 1mg/L phosphate, arsenic removal decreased gradually
      as pH increased from 4 to 6, and a sharp drop occurred at pH 7-9. The presence of
      10mg/L silicate had negligible effect on arsenic removal at pH 4-5 whereas
      decreased the arsenic removal at pH 6-9 and the decrease was more significant at
      higher pH. The presence of HA dramatically decreased the arsenic removal over the
      pH range of 6-9 and HA of higher concentration resulted in greater drop in
      arsenic removal. The effects of the competing anions on arsenic removal in the
      KMnO(4)-Fe(II) process were highly dependent on pH and the degree of these four
      anions influencing As(III) removal decreased in the following order,
      phosphate>humic acid>silicate>sulfate. Sulfate differed from the other three
      anions because sulfate decreased the removal of arsenic mainly by competitive
      adsorption while phosphate, silicate and HA decreased the removal of As(III) by
      competitive adsorption and sequestering the formation of ferric hydroxide derived
      from Fe(II).

PMID- 19573892
TI  - Uptake of arsenite by synthetic layered double hydroxides.
AB  - Two types of layered double hydroxides (LDHs), hydrotalcite and hydrocalumite
      with different composition of layers and interlayers were investigated for the
      removal of arsenite from solutions. The kinetics study showed that anion exchange
      process was very fast and apparently attained a steady-state in the range of 8-16
      h. Arsenite removal was found to be 87.5% and 83.6% with the nitrate forms of
      hydrotalcite and hydrocalumite, respectively. Layered double hydroxides
      synthesized at room temperature showed higher uptake than those synthesized by
      hydrothermal method due to small crystal size (high surface area) of the former.
      As expected, calcined hydrotalcite showed higher uptake than uncalcined carbonate
      form of hydrotalcite. The uptake process was anion exchange in hydrotalcite-type
      LDH as confirmed by X-ray diffraction (XRD) and scanning electron microscopy
      (SEM) but possibly some dissolution-reprecipitation occurred with hydrocalumite
      type LDH.

PMID- 19573893
TI  - Impact of WHO 2005 revised toxic equivalency factors for dioxins on the TEQs in
      serum, household dust and soil.
AB  - BACKGROUND: In 2005, the World Health Organization (WHO) - International
      Programme on Chemical Safety reevaluated the toxic equivalency factors (TEFs) for
      dioxin-like compounds and made changes that affect the calculation of the total
      toxic equivalent (TEQ). The impact of these changes on the TEQs for human blood
      and abiotic matrices such as soil and household dust has not been widely assessed
      or reported. METHODS AND RESULTS: Using a major exposure study which examined
      blood, household dust, and soil levels of dioxin-like compounds in several
      regions of Michigan, we found the mean total TEQ was significantly reduced by
      26%, 12% and 14% for serum, household dust, and soil, respectively, when the TEQ
      was based on the 2005 TEFs compared to the 1998 TEFs. The decrease in the serum
      total TEQ was largely due to the down-weighting of the TEFs for the majority of
      mono-ortho PCBs. In contrast, the decrease in the soil total TEQ was mostly due
      to the down-weighting of the TEF for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF)
      (1998 TEF=0.5, 2005 TEF=0.3). For household dust, the decrease in total TEQ was
      not due to any single TEF but was due to small changes in a number of compounds.
      There was a dramatic decrease (-88%) in the mean and 95th percentile for mono
      ortho PCB TEQ due to the 2005 TEFs. DISCUSSION: These findings suggest that
      comparisons between studies based on the TEQ-WHO(98) and TEQ-WHO(05) may need to
      consider an appropriate conversion factor to assure comparability. Furthermore,
      the changes in TEFs may have impact in locations where regulations of soil
      contamination are triggered by specific TEQ levels.

PMID- 19573895
TI  - Hyperglycaemia impairs antithrombin secretion: possible contribution to the
      thrombotic risk of diabetes.
AB  - Recent data support that diabetes might be a conformational disease. Certainly,
      hyperglycaemia causes a broad range of deleterious effects that might facilitate
      protein aggregation. We have evaluated the effects of hyperglycaemia on
      antithrombin, a conformationally sensitive serpin with a potent anticoagulant
      role. Moreover, these studies might also help to understand the thrombotic risk
      associated to diabetes. We incubated in vitro plasma and purified antithrombin
      and human hepatoma cells (HepG2) with methyl-glyoxal and glucose. Moreover, a
      mouse model of acute diabetes was generated with streptozotocin. Antigen, anti
      FXa activity, heparin affinity and conformational features of antithrombin were
      analysed. Histological and intracellular features and distribution of
      antithrombin in HepG2 and livers of mice were also evaluated. Hyperglycaemia in
      vitro induced a transition of antithrombin to a form with low heparin affinity
      that explained the loss of anticoagulant activity, without generation of abnormal
      conformers (polymers or latent antithrombin). However, these effects were not
      observed on circulating antithrombin from diabetic mice. In contrast,
      hyperglycaemia in vivo had significant effects on intracellular antithrombin,
      which was retained, forming microaggregates within the lumen of dilated cisterns
      of the endoplasmic reticulum. These effects explained the moderate type I
      deficiency observed in diabetic mice. Similar intracellular consequences were
      observed for another hepatic serpin, alpha1-antitrypsin. Our data further support
      that diabetes has conformational effects on structurally sensitive proteins.
      These effects on antithrombin, the main natural anticoagulant, might contribute
      to the hypercoagulable status of diabetic patients.

PMID- 19573894
TI  - The herbicide paraquat induces alterations in the elemental and biochemical
      composition of non-target microalgal species.
AB  - Huge quantities of pesticides are dispersed in the environment, affecting non
      target organisms. Since paraquat affects the photosynthetic process, the
      biochemical composition of affected species should be altered. The effect of
      paraquat on Chlamydomonas moewusii, a freshwater non-target species, was studied.
      After 48 h of herbicide exposure, growth rate, dry weight, and chlorophyll a and
      protein content were affected by paraquat concentrations above 0.05 microM. C/N
      ratio was also affected due to a decrease in nitrogen content in the dry biomass,
      while the carbon content remained constant for all paraquat concentrations
      assayed. Enzymes involved in nitrogen assimilation were affected by paraquat,
      being nitrate reductase activity more sensitive to paraquat than nitrite
      reductase. Based on the results obtained in the present study, paraquat exerts
      adverse effects upon a common freshwater green microalga, thus the application of
      this herbicide for weed control must be carried out very carefully, so that any
      disturbance affecting algae will have severe repercussions on higher trophic
      levels and on the elemental biogeochemical cycles.

PMID- 19573896
TI  - Venous thromboembolism in African-Americans: a literature-based commentary.
AB  - Among the cardiovascular diseases and after ischemic heart disease and stroke,
      venous thromboembolism (VTE) is the third leading cause of death in the U.S. (3).
      Although VTE is seen across most ethnic groups in the U.S. as well as throughout
      the world, the rate varies. In the U.S., American Indians/Alaskan Natives as well
      as Asians have been reported to have a significantly lower rate of deep vein
      thrombosis (DVT) and pulmonary embolism (PE) as compared to blacks and whites. In
      sharp conrast blacks appear to have much higher rates than whites. Although these
      rate differences are thought in part by some to be attributable to disparities in
      diagnosis and care as well as genetics, it nevertheless is important to define as
      well as to understand the true incidence and impact so that both public health
      and clinical resources can be maximally utilized. The purpose of this commentary
      is to review the VTE burden in the U.S. with respect to ethnicity in terms of
      clinical demographics and genetics with particular emphasis on blacks.

PMID- 19573897
TI  - Effect of estrogen and progesterone on urodynamics in the conscious rat.
AB  - OBJECTIVES: To examine the effects of estrogen and/or progesterone on the
      cystometric profiles obtained using continuous-filling cystometry in the
      conscious Sprague-Dawley rat. METHODS: Sprague-Dawley rats underwent ovariectomy
      (OVX) and were compared with controls by conscious continuous-filling cystometry.
      The effect of estrogen (10 microg/kg/d for 14 days) and/or progesterone (10
      mg/kg/d for 14 days) replacement on OVX urodynamics was examined (n = 7-8/group).
      RESULTS: OVX rats demonstrated reduced micturition intervals and voided volumes
      compared with controls. These effects of OVX were reversed by estrogen
      replacement, but not by progesterone replacement. When combined with estrogen,
      progesterone functioned to partially antagonize the effects of estrogen in OVX
      rats. CONCLUSIONS: Estrogen enhances bladder capacity in the OVX rat and
      therefore is a likely contributor to the larger bladder capacity in the female
      compared with the male rat. Consistent with its established role in reproductive
      physiology, progesterone antagonizes the beneficial effects of estrogen on OVX
      rat urodynamics.

PMID- 19573898
TI  - Three-month-old boy with juvenile granulosa cell tumor of testis and ossifying
      renal tumor of infancy.
AB  - We describe a 3-month-old male infant who presented with gross hematuria and was
      found to have a renal mass and a testicular mass representing these two entities.
      This is the first case report of these two lesions presenting concomitantly.

PMID- 19573899
TI  - Defects in muscarinic receptor cell signaling in bladder urothelial cancer cell
      lines.
AB  - INTRODUCTION: To explore muscarinic receptor signaling in 4 bladder cancer cell
      lines, bladder urothelial cells (BUC) have been shown to release and respond to
      various putative neurotransmitters. METHODS: Reverse transcription-polymerase
      chain reaction was used to detect the presence of m1-m5 transcripts in the J82,
      RT4, T24, and 5637 lines of cancer BUC. Immunofluorescence was used to detect
      expression of m3 protein. Cancer and normal BUC were stimulated with carbachol
      (100 microM), a muscarinic agonist. Carbachol-evoked changes in intracellular
      calcium ([Ca(2+)](i)) levels were measured using fura-2 ratiometric
      microfluorimetry. Transfection of J82 cells with m3 plasmid was performed, and
      changes in carbachol-evoked [Ca(2+)](i) were re-examined. RESULTS: None of the
      cancer cell lines expressed m3 transcripts, unlike normal BUC, which expressed
      m3. None of the 4 bladder cancer cell lines responded to carbachol. However, 47%
      of normal BUC responded to carbachol. The m3-transfected J82 cells expressed both
      m3 transcript and protein. Thirteen percent of m3-transfected J82 cells responded
      to carbachol. CONCLUSIONS: This is the first description of altered muscarinic
      signaling in cancer BUC. Unlike normal BUC, bladder urothelial cancer cells
      neither expressed m3 transcript nor responded to carbachol, as measured by
      changes in [Ca(2+)](i). We could partially reverse this defect in one of the
      cancer cell lines, J82, by transfecting these cells with the m3 plasmid. Although
      the effects of muscarinic receptor signaling on urothelial cell are unknown, this
      signaling pathway may play a role in urothelial cell adhesion similar to that in
      keratinocytes.

PMID- 19573900
TI  - Agrammatic comprehension caused by a glioma in the left frontal cortex.
AB  - It has been known that lesions in the left inferior frontal gyrus (L. IFG) do not
      always cause Broca's aphasia, casting doubt upon the specificity of this region.
      We have previously devised a picture-sentence matching task for a functional
      magnetic resonance imaging (fMRI) study, and observed that both pars triangularis
      (L. F3t) of L. IFG (extending to pars opercularis (L. F3op)) and the left lateral
      premotor cortex (L. LPMC) are selectively involved in syntactic processing. The
      present study with lesion-symptoms mapping was conducted to examine whether the
      function of these regions is indeed critical for syntactic comprehension. Using
      the same picture-sentence matching task, we examined 21 patients with a glioma in
      the left frontal cortex but with no apparent disability in verbal/written
      communication or intelligence quotient. This task included three main conditions
      of sentence types: canonical/subject-initial active sentences, non
      canonical/subject-initial passive sentences, and non-canonical/object-initial
      scrambled sentences. The patients preoperatively underwent a high-resolution 3D
      MRI, and voxel-based lesion-symptom mapping was employed for the error rates
      data. We found that the patients with a lesion in L. F3op/F3t or L. LPMC showed
      differential patterns of condition-selective deficits in the comprehension of
      sentences. More specifically, the L. F3op/F3t-damaged patients had more profound
      deficits in the comprehension of non-canonical sentences, whereas the L. LPMC
      damaged patients had more profound deficits in the comprehension of object
      initial scrambled sentences. These results establish that a lesion in L. F3op/F3t
      or L. LPMC is sufficient to cause agrammatic comprehension.

PMID- 19573901
TI  - Changes in maternal depression are associated with MST outcomes for adolescents
      with co-occurring externalizing and internalizing problems.
AB  - The efficacy of Multisystemic therapy (MST) in treating adolescent aggression has
      been established, however, not all youth and their families benefit from MST. One
      reason for this treatment variability could be the failure to distinguish between
      different aggressive subtypes with different risk factors, developmental
      prognoses and treatment needs. We investigated whether changes in maternal
      depression over MST would lead to different outcomes for two aggressive subtypes:
      pure externalizers (EXT) and mixed externalizers/internalizers (MIXED). Forty-two
      EXT and 27 MIXED youth and their families underwent MST for six months. Maternal
      depression, youth externalizing and internalizing behaviour were assessed before
      and after MST. Results showed a marginally greater change in externalizing for
      EXT youth. In addition, reductions in maternal depression were related to
      successful treatment outcomes for MIXED youth only. Our findings have
      implications for MST clinicians, namely the importance of reducing depressive
      symptoms in mothers of MIXED youth to improve their outcomes.

PMID- 19573902
TI  - What parents don't know and how it may affect their children: qualifying the
      disclosure-adjustment link.
AB  - Recent research has identified adolescent disclosure to parents as a powerful
      predictor of adolescent adjustment. We propose, however, that the common
      operationalization of adolescent disclosure incorporates the two separate
      constructs of disclosure and secrecy, and predicted that the disclosure
      adjustment link can largely be explained by the unique contribution of secrecy
      from parents. A four-wave survey study among 309 adolescents tested these
      predictions. Factor analyses confirmed that disclosure and secrecy should be
      distinguished as two separate constructs. Moreover, in cross-lagged path
      analyses, only secrecy was a longitudinal predictor of adolescent internalizing
      (i.e., depression) and externalizing (i.e., delinquency) problems, disclosure was
      not. Secrecy consistently contributed to the longitudinal prediction of
      delinquency from early to middle adolescence, whereas it contributed to the
      prediction of depression only in early adolescence. Findings thus attest the
      importance of distinguishing between disclosure and secrecy and suggest that the
      disclosure-adjustment link may actually reflect a secrecy-maladjustment link.

PMID- 19573903
TI  - Brief report: Text bullying and traditional bullying among New Zealand secondary
      school students.
AB  - This descriptive study examined text and traditional bullying in New Zealand
      (NZ), and the relationship between text bullying and traditional bullying, and
      feeling unsafe at school. A self-report online survey assessed the frequency of
      bullying among 1169 15 year old secondary students, for five categories of
      bullying: text messages, rumors, exclusion, teasing, and physical bullying.
      Results show that in the school year assessed 47% reported having been bullied
      sometimes or often and 37% reported bullying others; 11% reported being text
      bullied, while 7% reported text bullying others. Students involved in text
      bullying were significantly more likely to be involved in traditional forms of
      bullying and were less likely to feel safe at school.

PMID- 19573905
TI  - Best pharmacological practice in prehospital intubation.

PMID- 19573904
TI  - Etomidate versus ketamine for rapid sequence intubation in acutely ill patients:
      a multicentre randomised controlled trial.
AB  - BACKGROUND: Critically ill patients often require emergency intubation. The use
      of etomidate as the sedative agent in this context has been challenged because it
      might cause a reversible adrenal insufficiency, potentially associated with
      increased in-hospital morbidity. We compared early and 28-day morbidity after a
      single dose of etomidate or ketamine used for emergency endotracheal intubation
      of critically ill patients. METHODS: In this randomised, controlled, single-blind
      trial, 655 patients who needed sedation for emergency intubation were
      prospectively enrolled from 12 emergency medical services or emergency
      departments and 65 intensive care units in France. Patients were randomly
      assigned by a computerised random-number generator list to receive 0.3 mg/kg of
      etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the
      emergency physician enrolling patients was aware of group assignment. The primary
      endpoint was the maximum score of the sequential organ failure assessment during
      the first 3 days in the intensive care unit. We excluded from the analysis
      patients who died before reaching the hospital or those discharged from the
      intensive care unit before 3 days (modified intention to treat). This trial is
      registered with ClinicalTrials.gov, number NCT00440102. FINDINGS: 234 patients
      were analysed in the etomidate group and 235 in the ketamine group. The mean
      maximum SOFA score between the two groups did not differ significantly (10.3 [SD
      3.7] for etomidate vs 9.6 [3.9] for ketamine; mean difference 0.7 [95% CI 0.0
      1.4], p=0.056). Intubation conditions did not differ significantly between the
      two groups (median intubation difficulty score 1 [IQR 0-3] in both groups;
      p=0.70). The percentage of patients with adrenal insufficiency was significantly
      higher in the etomidate group than in the ketamine group (OR 6.7, 3.5-12.7). We
      recorded no serious adverse events with either study drug. INTERPRETATION: Our
      results show that ketamine is a safe and valuable alternative to etomidate for
      endotracheal intubation in critically ill patients, and should be considered in
      those with sepsis. FUNDING: French Ministry of Health.

PMID- 19573906
TI  - Effects of a nuclear power plant thermal discharge on habitat complexity and fish
      community structure in Ilha Grande Bay, Brazil.
AB  - Fish communities and habitat structures were evaluated by underwater visual
      censuses a rocky location impacted by thermal discharge (I) and at two control
      locations, one in a Sargassum bed (C1) and the other in a rocky shore with higher
      structural complexity (C2). Habitat indicators and fish communities exhibited
      significant differences between the impacted and control locations, with the
      impacted one showing a significant decrease in fish species richness and
      diversity, as well as a decrease in benthic cover. At the I location, only 13
      fish species were described, and the average water temperature was 32+/-0.4
      degrees C, compared with 44 species at C1 (25.9+/-0.3 degrees C) and 33 species
      at C2 (24.6+/-0.2 degrees C). Significant differences in fish communities among
      locations were found by ANOSIM with Eucinostomus argenteus, Mugil sp. and
      Haemulon steindachneri typical of location I, while Abudefduf saxatilis,
      Stegastes fuscus and Malacoctenus delalandi were typical of the control
      locations. Our study shows that thermal pollution alters benthic cover and
      influences fish assemblages by altering composition and decreasing richness.

PMID- 19573907
TI  - The effect of collagen-binding NGF-beta on the promotion of sciatic nerve
      regeneration in a rat sciatic nerve crush injury model.
AB  - Nerve growth factor plays a critical role in peripheral nerve regeneration.
      However, the lack of efficient NGF delivery approach limits its clinical
      application. It has demonstrated in our previous work that the native human NGF
      beta (NAT-NGF) fused with a collagen-binding domain (CBD) could bind to collagen
      specifically. Since collagen is the major component of nerve extracellular
      matrix, we speculated that the collagen-binding NGF would target to nerve cells
      and improve their regeneration. In this report, we found that the fusion protein
      could specifically bind to endogenous collagen of the rat sciatic nerves and
      maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush
      injury model, we found that collagen-binding NGF could be retained and
      concentrated at the nerve injured site to promote nerve repair and enhance
      function recovery following nerve damage. Thus, the collagen-binding NGF could
      improve the repair of peripheral nerve injury.

PMID- 19573909
TI  - The use of platelet-rich plasma in bone reconstruction therapy.
AB  - The use of platelet-rich plasma (PRP) in bone reconstruction therapy was
      introduced in the late 1990s. Since then, many scientists and clinicians have
      employed it in orthopaedic and oral surgeries. Unfortunately, studies that
      analyze the use of PRP are somewhat controversial as some conclude that the use
      of PRP may favor bone regeneration and others conclude that the use of PRP is
      irrelevant. By listing and analyzing the biological effect that each factor
      released by the activated platelets can have in bone regeneration, the present
      review answers the question of why PRP may be useful in bone reconstruction
      therapy. Subsequently, by examining the studies that have both successfully and
      unsuccessfully utilized PRP, it suggests how PRP might be used in order to
      achieve successful results in orthopaedic and dental bone reconstruction
      surgeries.

PMID- 19573908
TI  - Zwitterionic carboxybetaine polymer surfaces and their resistance to long-term
      biofilm formation.
AB  - In this work, we report a systematic study of zwitterionic poly(carboxybetaine
      methacrylate) (pCBMA) grafted from glass surfaces via atom transfer radical
      polymerization (ATRP) for their resistance to long-term bacterial biofilm
      formation. Results show that pCBMA-grafted surfaces are highly resistant to non
      specific protein adsorption (fibrinogen and undiluted blood plasma) at 25, 30 and
      37 degrees C. Long-term (over 24 h) colonization of two bacterial strains
      (Pseudomonas aeruginosa PAO1 and Pseudomonas putida strain 239) on pCBMA surface
      was studied using a parallel flow cell at 25, 30 and 37 degrees C. Uncoated glass
      cover slips were chosen as the positive reference. Results show that pCBMA
      coatings reduced long-term biofilm formation of P. aeruginosa up to 240 h by 95%
      at 25 degrees C and for 64 h by 93% at 37 degrees C, and suppressed P. putida
      biofilm accumulation up to 192 h by 95% at 30 degrees C, with respect to the
      glass reference. The ability of pCBMA coatings to resist non-specific protein
      adsorption and significantly retard bacterial biofilm formation makes it a very
      promising material for biomedical and industrial applications.

PMID- 19573910
TI  - pH-dependent modulation of fibroblast adhesion on multilayers composed of
      poly(ethylene imine) and heparin.
AB  - Adhesion of tissue cells is a prerequisite for their growth and differentiation
      but prevents also apoptosis. Here the layer-by-layer technique (LbL) was used to
      design multilayer structures of poly(ethylene imine) (PEI) and heparin (HEP) on
      glass as model biomaterial to control the adhesion of primary human dermal
      fibroblasts. Distinct surface features like wettability, charge and lateral
      structures were controlled by changing the pH value of the HEP solution during
      multilayer assembly to acidic, neutral or alkaline values. While plain terminal
      layers were rather cytophobic, the pre-adsorption of serum or fibronectin (FN)
      caused a distinct change in cell morphology in dependence on the pH setup. The
      effect of serum was more prominent on PEI layers probably due to their positive
      surface charge, whereas the effect of FN was more pronounced on HEP terminated
      multilayers possibly due to its ability to bind FN specifically. Those layers
      which hampered cell adhesion also inhibited growth of human fibroblasts under
      serum conditions. Conversely, on layers where cell adhesion was increased also an
      elevated growth and, thus, metabolic activity was observed.

PMID- 19573911
TI  - Mixed-mode fracture of human cortical bone.
AB  - Although the mode I (tensile opening) fracture toughness has been the focus of
      most fracture mechanics studies of human cortical bone, bones in vivo are
      invariably loaded multiaxially. Consequently, an understanding of mixed-mode
      fracture is necessary to determine whether a mode I fracture toughness test
      provides the appropriate information to accurately quantify fracture risk. In
      this study, we examine the mixed-mode fracture of human cortical bone by
      characterizing the crack-initiation fracture toughness in the transverse
      (breaking) orientation under combined mode I (tensile opening) plus mode II
      (shear) loading using samples loaded in symmetric and asymmetric four-point
      bending. Whereas in most structural materials, the fracture toughness is
      increased with increasing mode-mixity (i.e., where the shear loading component
      gets larger), in the transverse orientation of bone the situation is quite
      different. Indeed, the competition between the maximum applied mechanical mixed
      mode driving force and the weakest microstructural paths in bone results in a
      behavior that is distinctly different to most homogeneous brittle materials.
      Specifically, in this orientation, the fracture toughness of bone is markedly
      decreased with increasing mode-mixity.

PMID- 19573912
TI  - Regulation of store-operated Ca2+ entry in pulmonary artery smooth muscle cells.
AB  - Store-operated Ca2+ entry (SOCE) is an important mechanism for Ca2+ influx in
      smooth muscle cells; however the activation and regulation of this influx pathway
      are incompletely understood. In the present study we have examined the effect of
      several protein kinases in regulating SOCE in pulmonary artery smooth muscle
      cells (PASMCs) of the rat. Inhibition of protein kinase C with chelerythrine
      (3microM) potentiated SOCE by 47+/-2%, while the tyrosine kinase inhibitors
      genistein (100microM) and tyrphostin 23 (100microM) caused a significant
      reduction in SOCE of 55+/-9% and 43+/-7%, respectively. It has been proposed that
      Ca2+-insensitive phospholipase A(2) (iPLA(2)) is involved in the activation of
      SOCE in many different cell types. The iPLA(2) inhibitor, bromoenol lactone had
      no effect on SOCE, suggesting that this mechanism was not involved in the
      activation of the pathway. The calmodulin antagonists, calmidazolium (CMZ)
      (10microM) and W-7 (10microM) appeared to potentiate SOCE in PASMCs. Further
      investigation established that CMZ was actually activating a Ca2+ influx pathway
      that was independent of the filling state of the sarcoplasmic reticulum. The CMZ
      activated Ca2+ influx was blocked by Gd3+ (10microM), but unaffected by 2-APB
      (75microM), indicating a pharmacological profile distinct from the classical SOCE
      pathway.

PMID- 19573913
TI  - Norepinephrine regulates arginine vasopressin secretion in hypothalamic
      paraventricular nucleus relating with pain modulation.
AB  - Our previous study has pointed that arginine vasopressin (AVP) and norepinephrine
      (NA) are two most important bioactive substances that play a role in hypothalamic
      paraventricular nucleus (PVN) regulating pain process. The communication was
      designed to investigate the interaction between AVP and NA in the rat PVN during
      the pain process. We used the potassium iontophoresis inducing tail-flick to test
      the pain threshold, PVN push-pull perfusion to collect the samples, high
      performance chromatography (HPLC) to determine the NA concentration and
      radioimmunoassay (RIA) to measure the AVP concentration. The results showed that
      (1) pain stimulation increased both NA and AVP concentrations in the PVN
      perfusion liquid; (2) PVN administration of l-glutamate sodium increased AVP, not
      NA concentration in the PVN perfusion liquid; (3) AVP or d(CH(2))(5)Tyr(Et)DAVP
      (AVP-receptor antagonist) neither changed pain threshold, nor influenced NA
      concentration in the PVN perfusion liquid; (4) Microinjection of NA into PVN
      could increase pain threshold in a dose-dependent manner, while PVN
      administration with phentolamine (alpha-receptor antagonist), not propranolol
      (beta-receptor antagonist) decreased pain threshold; (5) Administration of NA
      increased AVP concentration, while phentolamine, not propranolol decreased AVP
      concentration in the PVN perfusion liquid. These data suggested that it is
      through alpha-receptor rather than beta-receptor, NA induced PVN secretion of AVP
      that was delivered to the related brain regions to participate in pain
      modulation.

PMID- 19573914
TI  - How do JAK2-inhibitors work in myelofibrosis: an alternative hypothesis.
AB  - The clinical efficacy of JAK2-inhibitors in patients with myelofibrosis, that
      involves a rapid and massive reduction of spleen enlargement and improvement of
      clinical symptoms, is not accompanied by significant modifications of hematologic
      parameters nor of the burden of JAK2V617F allele. Furthermore, clinical
      improvement has been reported to occur irrespective of patient's JAK2-mutated
      status. On the other hand, dramatic changes in plasma cytokine levels have been
      observed. Based on available information about the role of cytokines in the
      pathogenesis of myelofibrosis, the hypothesis that the clinical efficacy of JAK2
      inhibitors could be mainly ascribed to a general down-regulation of cytokine
      production and cytokine signaling is discussed.

PMID- 19573915
TI  - Acute lymphoblastic leukemia (ALL) with t(8;14)(q11.2;q32) in an elderly patient.
AB  - Acute lymphoblastic leukemia (ALL) with chromosome aberration t(8;14)(q11.2;q32)
      mostly affects patients younger than 20 years old. One third of patients with
      this translocation have been reported to have Down syndrome. This translocation
      has been reported rarely in patients over the age of 50. Here we report a 71-year
      old male ALL patient who carried t(8;14)(q11.2;q32). Fluorescence in situ
      hybridization (FISH) analysis revealed the involvement of CCAAT enhancer-binding
      protein delta (CEBPD) gene on chromosome 8, and IgH gene on chromosome 14. This
      case provides a new aspect for considering this clinical entity.

PMID- 19573916
TI  - Lack of association between the MDM2 promoter polymorphism SNP309 and clinical
      outcome in chronic lymphocytic leukemia.
AB  - The 309T>G polymorphism in the promoter region of the MDM2 gene, known as SNP309,
      has recently been suggested as an unfavorable prognostic marker in chronic
      lymphocytic leukemia (CLL) although this has been questioned. To investigate this
      further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated
      the results with established CLL prognostic factors, time to treatment and
      overall survival. In this Swedish cohort, no association existed between any
      particular MDM2 SNP309 genotype, overall survival and time to treatment.
      Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet
      stage, IGHV mutational status and recurrent genomic aberrations. In summary, this
      study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL.

PMID- 19573917
TI  - NB4 cells treated with all-trans retinoic acid generate toxic reactive oxygen
      species that cause endothelial hyperpermeability.
AB  - Retinoic acid syndrome (RAS) is a serious complication during induction therapy
      with all-trans retinoic acid (RA) in patients with acute promyelocytic leukemia.
      In this study, we examined whether reactive oxygen species (ROS) were involved in
      capillary leak phenomenon in RAS, using NB4 cells. When cells were stimulated by
      phorbol 12-myristate 13-acetate, RA-treated cells with matured myeloperoxidase
      produced toxic ROS, such as singlet oxygen, hypochlorous acid and hydroxyl
      radical, and brought about endothelial hyperpermeability. Leukemic cells from a
      patient also produced toxic ROS. These findings indicated that toxic ROS
      contribute to the development of capillary leak phenomenon in RAS.

PMID- 19573918
TI  - Cadmium toxicity to embryonic-larval development and survival in red sea bream
      Pagrus major.
AB  - At 18 degrees C and 33 psu, 24 and 48 h LC(50) values of cadmium (Cd) for red sea
      bream Pagrus major embryos were 9.8 and 6.6 mgl(-1), respectively, while 24, 48,
      72, and 96 h LC(50) values for larvae were 18.9, 16.2, 8.0, and 5.6 mgl(-1),
      respectively, indicating that embryos were more sensitive to Cd toxicity than
      larvae. Cd concentrations at > or =0.8 mgl(-1) led to low hatchability (0-90% in
      > or =0.8 mgl(-1) solutions vs. 97-100% in lower ones), delay in time to hatch,
      high mortality (38-100% vs. 1-10%), morphological abnormality (42-100% vs. 1
      10%), reduced length (3.55-3.60 vs. 3.71-3.72 mm) in the embryos and larvae. They
      were Cd concentration dependent and potential biological significant endpoints
      for assessing the risk of Cd to aquatic organisms. Heart beat and yolk absorption
      of the larvae were significantly inhibited at some high concentrations but they
      were not as sensitive as other endpoints to Cd exposure.

PMID- 19573920
TI  - Systems of care. Introduction.

PMID- 19573919
TI  - Using the larvae nematode Caenorhabditis elegans to evaluate neurobehavioral
      toxicity to metallic salts.
AB  - In this study, we investigated the locomotion behavior changes at different
      developmental stages in Caenorhabditis elegans exposed to metals for 4h. No
      obvious differences could be observed in young adults exposed to examined metals,
      and only exposure to 100 microM of examined metals could significantly decrease
      the locomotion behaviors of L4 larvae. In contrast, exposure to 50 and 100 microM
      of examined metals induced noticeable repression of locomotion behaviors at L1-L3
      larval stages, and a significant decrease of locomotion behaviors could be
      observed in L1 larvae exposed to Pb and Hg, and in L2 larvae exposed to Hg at the
      concentration of 2.5 microM. Moreover, the L1-, L2-, and L3-larvae exposed to
      metals for 4h exhibited similar neurobehavioral toxicity manner to L4-larvae
      exposed to metals for 24h. Therefore, younger larvae showed more severe deficits
      in neurobehavioral phenotypes than L4 larvae and young adults in metal-exposed
      nematodes.

PMID- 19573921
TI  - Middle ear adenomatous tumor: a not so rare glomus tympanicum-mimicking lesion.
AB  - BACKGROUND AND PURPOSE: Middle ear adenomatous tumors (MEAT) are rare tumors
      which can be begin or malignant and can present a neuroendocrine differentiation.
      Their radiological aspect is very similar to glomus tympanicum (GT) which are the
      most common tumoral lesions of the middle ear. We present several radiological
      and clinical findings that could help radiologists to accurately identify MEAT.
      MATERIAL AND METHODS: We retrospectively reviewed the radiological and clinical
      findings of three patients with MEAT and of eight patients with GT. Diagnostic
      was obtained after surgical resection in all cases. All patients had high
      resolution CT and MR of the middle ear associated with a subtracted digital
      carotid angiography. Tumor location, size, extension, signal intensity, and
      enhancement were analysed. From the medical records of the patients, clinical
      manifestations (hearing loss, tinnitus), evolution length and recurrences were
      noted. RESULTS: MEAT and GT appeared as tissular lesion with significant
      enhancement on CT and MR. A vascular blush was present on angiography in all
      cases of GT and absent from all cases of MEAT. A close relationship between the
      tumor and the Jacobson's nerve or its branches was identified in all cases of GT.
      Pulsatile tinnitus was present in all patients with GT and absent in all patients
      with MEAT. CONCLUSION: A middle ear tissular lesion clearly separated from the
      Jacobson nerve or its branches, showing significant enhancement after contrast
      medium injection but with a normal angiography, should make one suspicious for
      MEAT.

PMID- 19573922
TI  - [Dural inflammatory pseudotumor: report of a single case].

PMID- 19573923
TI  - Optimal carotid artery coverage for carotid plaque CT-imaging in predicting
      ischemic stroke.
AB  - OBJECTIVE: To determine the optimal spatial coverage for CT-imaging of carotid
      atherosclerosis, allowing the most accurate prediction of the associated risk of
      ischemic stroke. METHODS: In a cross-sectional study, we retrospectively
      identified 136 consecutive patients admitted to our emergency department with
      suspected stroke who underwent a CT-angiogram (CTA) of the cervical and
      intracranial carotid arteries. CTA studies of the carotid arteries were processed
      using a custom, CT-based automated computer classifier algorithm that
      quantitatively assesses a battery of carotid CT features. We used this algorithm
      to individually analyze different lengths of the common and internal carotid
      arteries for carotid wall features previously shown to be significantly
      associated with the risk of stroke. Acute stroke patients were categorized into
      "acute carotid stroke patients" and "non-acute carotid stroke patients"
      independently of carotid wall CT features. Univariate and multivariate analyses
      were used to compare the different spatial coverages in terms of their ability to
      distinguish between the carotid stroke patients and the noncarotid stroke
      patients using a receiver-operating characteristic curve (ROC) approach. RESULTS:
      The carotid wall volume was excellent at distinguishing between carotid stroke
      patients and noncarotid stroke patients, especially for coverages 20mm or less.
      The number and location of lipid clusters had a good discrimination power, mainly
      for coverages 15mm or greater. Measurement of minimal fibrous cap thickness was
      most associated with carotid stroke when assessed using intermediate coverages.
      Typically, a 20mm coverage on each side of the carotid bifurcation offered the
      optimal compromise between the individual carotid features. CONCLUSION: We
      recommend assessment of 20mm of each side of the carotid bifurcation to best
      characterize carotid atherosclerotic disease and the associated risk of ischemic
      stroke.

PMID- 19573924
TI  - Drinking water quality: an in vitro approach for the assessment of cytotoxic and
      genotoxic load in water sampled along distribution system.
AB  - An in vitro approach was performed to assess the quality of drinking water
      collected at two treatment/distribution networks located near the source (Plant
      #1) and the mouth of River Po (Plant #2). The water was sampled at different
      points of each distribution network, before (raw water) and after the chlorine
      dioxide disinfection, and in two points of the pipeline system to evaluate the
      influence of the distribution system on the amount and quality of the
      disinfection by-product. Cytotoxicity and genotoxicity of water extracts were
      evaluated in human peripheral lymphocytes and Hep-G2 cells by the use of the
      micronucleus (MN) test and Comet assay. Raw water samples of both plants induced
      cytotoxic effects, but not the increases of MN frequency in Hep-G2 cells and in
      human lymphocytes. Increases of DNA damage in human leukocytes was detected by
      Comet assay for raw water of Plant #2 at concentration > or = 0.25 Leq/mL. The
      disinfection process generally has reduced the toxicity of water samples, even if
      potential direct DNA-damaging compounds have been detectable in drinking water
      samples. The proposal approach, if currently used together with chemical
      analysis, can contribute to improve the monitoring drinking water.

PMID- 19573925
TI  - Levels and regional trends of persistent organochlorines and polybrominated
      diphenyl ethers in Asian breast milk demonstrate POPs signatures unique to
      individual countries.
AB  - Human breast milk samples collected in 2007-2008 from four countries, Vietnam
      (Hanoi), China (Beijing), Korea (Seoul) and Japan (Sendai, Kyoto and Takayama),
      were analyzed for persistent organic pollutants (POPs) such as
      dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane-related
      compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB),
      polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs).
      Comparing with previous surveys, the present study indicates that the DDTs in
      breast milk from China and Vietnam had gradually decreased during the last
      decade, but were still 5-10 times higher than those in other nations. The ratios
      of p,p'-DDE/p,p'-DDT and o,p'-DDT/p,p'-DDT were higher in Beijing than in the
      other countries, suggesting that there is less fresh intake of commercial DDT
      products and a possible exposure to dicofol in China. CHL and PCB levels were
      relatively higher in mothers from Japan, whereas beta-HCH and HCB were more
      common in Chinese women. In Japan, it is suspected that mothers in the
      urban/coastal area (Sendai) were more continuously exposed to organochlorine
      pesticides (OCPs) than mothers in the rural/inland area (Takayama). In addition,
      OCP levels in primiparae were significantly higher than those in multiparae from
      Japan and Korea. These indicate that both parity and regional factors are major
      determinants of the levels of OCPs and PCBs in human milk. On the other hand,
      higher concentrations of PBDEs were observed in mothers' milk from Korea. The
      congener was dominated by BDE-47 (43-54%), followed by BDE-153 (23-33%) in all
      regions except for Beijing where BDE-28 (23%) was relatively abundant. In
      Japanese breast milk, regional and parity-dependent distributions were not
      observed for PBDEs. Among PBDE congeners, age-dependency was observed for BDE
      153, which was negatively correlated (p<0.05) to the age of mothers in Kyoto (17
      participants were housewives), while it increased with age in Sendai (10
      participants were clerks). No such correlation was seen for BDE-47, indicating
      that BDE-47 was ingested and assimilated via different kinetics or routes from
      BDE-153 in Japan.

PMID- 19573926
TI  - Expression regulation and functional characterization of a novel interferon
      inducible gene Gig2 and its promoter.
AB  - Grass carp hemorrhagic virus (GCHV)-induced gene 2 (Gig2) is a novel gene
      previously identified from UV-inactivated GCHV-treated Carassius auratus
      blastulae embryonic (CAB) cells, suggesting that it should play a pivotal role in
      the interferon (IFN) antiviral response. In this study, a polyclonal anti-Gig2
      antiserum was generated and used to study the inductive expression pattern by
      Western blot analysis, showing no basal expression in normal CAB cells but a
      significant up-regulation upon UV-inactivated GCHV, polyinosinic:polycytidylic
      acid (Poly I:C) and recombinant IFN (rIFN). However, constitutive expression of
      Gig2 is observed in all tested tissues from grass carp (Ctenopharyngodon
      idellus), and Poly I:C injection increases the relative amount of Gig2 protein in
      skin, spleen, trunk kidney, gill, hindgut and thymus. Moreover, the genomic
      sequence covering the whole Gig2 ORF and the upstream promoter region were
      amplified by genomic walking. Significantly, the Gig2 promoter contains three IFN
      stimulated response elements (ISREs), nine GAAA/TTTC motifs and five gamma-IFN
      activating sites (GAS), which are the characteristics of genes responsive to both
      type I IFN and type II IFN. Subsequently, the complete Gig2 promoter sequence was
      cloned into pGL3-Basic vector, and its activity was measured by luciferase assays
      in the transfected CAB cells. The Gig2 promoter-driven construct is highly
      induced in CAB cells after treatment with Poly I:C or rIFN, and the functional
      capability is dependent on IFN regulatory factor 7 (IRF7), because its activity
      can be stimulated by IRF7. Collectively, the data provide strong evidence that
      Gig2 is indeed a novel IFN inducible gene and its expression is likely dependent
      on IRF7 upon Poly I:C or IFN.

PMID- 19573927
TI  - Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition
      of CpG oligodeoxynucleotides.
AB  - Similar to mammalian species, chickens show marked immunological responses to CpG
      oligodeoxynucleotides (ODNs) both in vivo and in vitro. In mammals, the receptor
      for ODNs has been demonstrated to be TLR9; however, an orthologue to mammalian
      TLR9 is absent in the chicken genome. In this study, chicken TLRs 7, 15 and 21
      were expressed in mammalian HEK-293T cells; expression of TLR21 but not TLR7 or
      15 resulted in marked NF-kappaB activation upon stimulation with exogenous ODN.
      This activation was not observed when cells were stimulated by TLR agonists other
      than ODNs. In addition, responsiveness of the ectopically expressed TLR21
      demonstrated similar kinetics of activation as reported for mammalian TLR9 and
      was dependent on the nucleotide sequence of the ODN. The same ODN specificity was
      observed for chicken HD11 macrophage when ODN mediated activation was monitored
      by up-regulation of IL1, IL6 and iNOS transcripts. Furthermore, when TLR21, but
      not TLR15, was partially silenced in HD11 cells by RNA interference, ODN mediated
      responses were reduced. TLR21-mediated NF-kappaB activation in HEK-293T cells was
      inhibited by bafilomycin A suggesting that endosomal maturation is required for
      TLR21 activation and observations by confocal microscopy and digestion with
      endoglycosidase H suggest TLR21 localizes to the endoplasmic reticulum (ER) of
      resting cells. Expression of TLR21 transcripts was found in all chicken tissues
      examined but was significantly less in the lung and small intestine of newly
      hatched birds. Two of the leucine rich repeat regions (LRRs) of TLR21 showed
      homology with a LRR conserved within mammalian TLR9 and implicated in ligand
      binding. We hypothesize that avian TLR21 plays a similar role to that of
      mammalian TLR9 and enables recognition of microbial DNA as a danger signal
      resulting in downstream innate and adaptive immune responses.

PMID- 19573928
TI  - It's all in the cards: effect of stimulus manipulation on Wisconsin Card Sorting
      Test performance in schizophrenia.
AB  - Patients with schizophrenia can be taught the Wisconsin Card Sorting Test (WCST)
      sorting rules based upon expanded feedback. However, few task manipulations have
      been reported that differentially improve patient performance without altering
      the nature of feedback provided. The present study tests the hypothesis that
      deficits in WCST performance in schizophrenia reflect, in part, impaired ability
      to manipulate abstract stimulus features, rather than impaired ability to utilize
      feedback. We developed a modified stimulus set - the Rockland Face Sorting Test
      (RFST) - in which abstract shapes were replaced with faces, which we hypothesized
      would be more tractable to sorting by patients. Task rules and feedback remained
      unchanged. Relative RFST and WCST performance was examined in 19 patients as well
      as 15 normative controls. A comparison group of 15 patients received only
      repeated WCST administrations. Patients performed significantly better on the
      RFST vs. the WCST in categories completed, total correct responses and conceptual
      level responses, whereas no improvement was seen in either the normative or
      repeated WCST comparison groups. Furthermore, progressive improvement was seen
      following repeated RFST administration. These findings demonstrate that stimulus
      characteristics, as well as executive deficits, contribute to impaired WCST
      performance in schizophrenia.

PMID- 19573930
TI  - Molecular characterization of duck interleukin-17.
AB  - Interleukin-17 (IL17), belonging to the Th17 family, is a proinflammatory
      cytokine produced by activated T cells. A 1034bp cDNA encoding duck IL17 (duIL17)
      was cloned from Con A-activated splenic lymphocytes of ducks. The encoded
      protein, which is predicted to consist of 169 amino acids, has a molecular weight
      of 18.8kDa and includes a 29 residue NH(2)-terminal signal peptide, a single
      potential N-linked glycosylation site, and six cysteine residues that are
      conserved in mammalian IL17. The duIL17 shared 84% amino acid sequence identity
      with the previously described chicken IL17 (chIL17), 36-47% to mammalian
      homologues, and open reading frame 13 of Herpesvirus saimiri (HVS13). The genomic
      structure of duIL17 was quite similar to its chicken and mammalian counterparts.
      The duIL17 mRNA expression was detected only in Con A-activated splenic
      lymphocytes by RT-PCR, although its expression was undetectable in a variety of
      normal tissues. Two mAbs against chIL17 showed cross-reactivity with duIL17 as
      detected by indirect ELISA and Western blot analysis. These findings indicate
      that the structure of IL17 is highly conserved among poultry, and two mAbs
      detecting common epitopes of IL17 are available for molecular and immunological
      studies of IL17 in birds.

PMID- 19573931
TI  - Lack of association between antisperm antibodies and language dysfunction in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the single most common cause of primary dementia.
      Language-based frontotemporal dementia, another type of primary dementia, is
      known as primary progressive aphasia (PPA). Although the cardinal feature of AD
      is a progressive loss of memory, many patients with AD also present with language
      impairment. Moreover AD and PPA have partially shared pathophysiology. Recently,
      it was suggested that a history of vasectomy might be a risk factor for PPA, by
      immune responses to sperm or antisperm antibody (ASA), which has long been known
      to have antigenic property. As ASAs could develop naturally in both men and
      women, we studied the relation between the presence of ASAs and cognitive
      function in AD. A total of 86 elderly were selected (46 patient with AD, 20 with
      mild cognitive impairment, and 20 without cognitive dysfunction) and were
      assessed for the presence of ASAs with neuropsychological evaluation. However,
      there were no significant differences in the distribution of ASAs according to
      cognitive status or language function status. Thus, the current study does not
      support the association between the immune responses and language dysfunction in
      AD.

PMID- 19573929
TI  - Locus of control: relation to schizophrenia, to recovery, and to depression and
      psychosis -- A 15-year longitudinal study.
AB  - The present prospectively designed 15-year longitudinal research was conducted to
      study whether locus of control is linked to diagnosis, to major symptoms, to
      functioning and recovery, and to personality for schizophrenia patients,
      depressive patients, and patients with other major disorders. The research
      studied 128 patients from the Chicago Follow-up Study at the acute phase and
      reassessed them 5 times over a 15-year period. Patients were evaluated on locus
      of control, global outcome, recovery, premorbid developmental achievements,
      psychosis, diagnosis, depression, and personality variables. 1) After the acute
      phase, schizophrenia patients were not more external than other diagnostic
      groups. 2) Internality is significantly associated with increased recovery in
      schizophrenia. 3) A more external locus of control was significantly related to
      depression. 4) The relationship between externality and psychosis was
      significant. In severe psychiatric disorders a more external locus of control is
      not specific to schizophrenia and after the acute phase is not associated with
      one particular diagnostic group. A more external locus of control is
      significantly related to fewer periods of recovery, to both depressed mood and
      psychosis, and to various aspects of personality.

PMID- 19573932
TI  - Patient clock drawing and accuracy of self-report compared with chart review for
      colorectal cancer (CRC) screening.
AB  - The purpose of this study was to test the accuracy of patient colorectal cancer
      (CRC) screening self-report and CRC screening documented in their medical record
      for those who are cognitively impaired and those who are not based on the clock
      drawing task. A cross-sectional study where patient survey and medical record
      information were linked was conducted in 16 primary care offices. Of the 960
      patients mailed questionnaires, there were 493 respondents who completed the
      questionnaire and clock drawing, had a chart review, and had no help in drawing
      the clock or completing the questionnaire. Chart review was conducted for CRC
      screening in physician offices. Clock drawings were scored 0-7 according to the
      Watson method. Accuracy of ever being screened for CRC or being up-to-date for
      CRC screening was determined by comparing self-report with medical records and
      calculating sensitivity, specificity, positive and negative predictive values,
      false positive rate, and false negative rate. Seventy-five clocks were abnormal,
      scoring 4 or more. Agreement between self-reported colonoscopy and medical record
      review was higher in subjects with normal clock drawings than those with abnormal
      clock drawings. When examining predictors of agreement/disagreement for
      colonoscopy screening, abnormal clock drawing was the single predictor for higher
      disagreement.

PMID- 19573933
TI  - Leisure and distress in caregivers for elderly patients.
AB  - Caregiving for the elderly has been linked to mental and physical problems in
      those providing the care. The aim of this study is to analyze the effects of
      leisure on caregiver's burden and mental health. Drawing on the stress and coping
      model, 134 caregiver/care-recipient dyads were assessed. In addition to
      caregivers' perception of their leisure time, social support, burden and mental
      health, care-recipients' functional and mental status were also measured. The
      results of a set of hierarchical regression analyses showed that caregivers'
      perceptions of their leisure time were significantly negatively related to burden
      and mental health problems (p<0.01), even after socio-demographic variables, care
      recipient's functional status and caregiver's social support had been controlled.
      The results of this study suggest that leisure time has a significant impact on
      caregiver's psychological well-being, and appears to be an important issue for
      buffering caregiver distress.

PMID- 19573934
TI  - Older people's use of pre-hospital emergency medical services in Izmir, Turkey.
AB  - The aim of this study is to determine the use of pre-hospital emergency medical
      services (EMS) in elderly people aged 65 years and over in Izmir, Turkey. In this
      descriptive study, older patients admitted to pre-hospital EMS of Izmir Province
      Health Directorate between 2004 and 2005 years was evaluated through the review
      of Emergency Call Registry Forms. The study data included socioeconomic
      characteristics, reasons of calling, distribution of calling times in the day,
      distribution of ambulance callers and preclinical diagnosis. A total of 34% of
      the subjects admitted to pre-hospital EMS were 65 years old and over. The rate of
      the use of ambulance services was 68.9/1000 population/year. The rate of pre
      hospital EMS use for older persons living in urban areas was significantly higher
      than that of those living in rural areas. The most frequent pre-hospital EMS
      caller were persons in family (70.7%), and utilization of ambulance services was
      the highest in winter. Medically related incidents accounted for 89.1% of all
      emergency ambulance calls and cardiovascular diseases accounted for most common
      cause (32.6%) of calls. The utilization rate of pre-hospital EMS among older
      persons was approximately four times higher than that of the younger age groups.

PMID- 19573935
TI  - Simultaneous treatment of a fistula and a stenosis at right coronary artery: one
      stone two birds.
AB  - Coronary artery fistulas are abnormal and rare communications between a coronary
      artery and a cardiac chamber or a major vessel. Some devices have been designed
      to treat coronary fistulas percutaneously like coils and vascular occlusion
      devices. But most of these have been developed for fistulas unaccompanied by
      coronary artery disease. It is rational to treat a coronary fistula adjacent to a
      stenosis with one covered stent graft. This report describes a case of a coronary
      to-pulmonary artery fistula with an adjacent right coronary artery stenosis that
      were both successfully treated by a single expanded polytetrafluoroethylene
      covered stent graft.

PMID- 19573936
TI  - What's up Doc? Or about running about.
AB  - Symptomatic cardiac arrhythmias are a very disturbing sign to well-trained
      athletes, warranting prompt diagnosis and therapy, preferably not interfering
      with their physical performance at the time. A case is presented where exercise
      induced atrial flutter occurred in the aftermath of a viral infection. Basic
      tools like holter-monitoring and a heart-rate meter provided insight and
      understanding. Arrhythmia management really is a joint venture between athlete
      and physician to provide a tailor-made solution, using interventional techniques,
      cardiovascular conditioning and sometimes a pharmaceutical agent, all together
      carefully auto-monitored.

PMID- 19573937
TI  - Profound myocardial ischemia associated to occlusion of the right coronary
      artery.
AB  - A 75-year-old man with hypertension, hypercholesterolemia and history of coronary
      artery disease was admitted to the hospital because of sudden loss of
      consciousness. The patient suffered an acute myocardial infarction seven years
      before this admission, which was treated with percutaneous transluminal coronary
      angioplasty and stent implantation in the right coronary artery. The initial
      electrocardiogram showed a complete atrioventricular block, with narrow
      ventricular complexes at a rate of 40 bpm. The next electrocardiogram, obtained
      after the administration of atropine, showed a sinus rhythm at 84 bpm with first
      degree atrioventricular block, obvious ST-segment elevation on leads II, III,
      aVF, V3 to V6, and electrical alternation of the ST-segment. Subsequently, he
      suffered three episodes of ventricular fibrillation which were successfully
      defibrillated. The ST-segment elevation improved after sublingual nitroglycerine
      and the patient underwent urgent coronary angiography, which showed a critical
      stenosis in the middle part of the right coronary artery with a lot of thrombus
      material in the site of the previous stent. The rest of the coronary arteries did
      not reveal significant lesions. Thrombus aspiration and balloon angioplasty were
      successfully performed without residual stenosis. The ST-elevation alternans is a
      rare phenomenon which was initially described in the setting of coronary artery
      spasm. It is believed to be associated to profound myocardial ischemia,
      particularly in relation with occlusions of the left anterior descending coronary
      artery, and to the occurrence of malignant ventricular arrhythmia and sudden
      cardiac death.

PMID- 19573938
TI  - Mortality and morbidity of newly diagnosed heart failure with preserved systolic
      function treated with beta-blockers: a propensity-adjusted case-control
      populational study.
AB  - BACKGROUND: The effect of treatment with beta-blockers on the prognosis of
      patients newly diagnosed with heart failure with preserved systolic function (HF
      PSF) is unknown. OBJECTIVES: To analyze the relationship of commencing treatment
      with the beta-blockers bisoprolol or carvedilol (CT-betaB) with the mortality and
      the morbidity of newly diagnosed HF-PSF. METHODS: Prospective propensity-adjusted
      cohort study over 5 years on 1085 adults diagnosed with HF-PSF for the first
      time, in an integrated university-based health organization in Spain. The
      independent relationship between CT-betaB and mortality and morbidity was
      analyzed, stratifying patients for comorbidity, after a multivariable adjustment
      for potential confounders. RESULTS: The 378 patients (34.8%) who CT-betaB were
      more frequently older women, with more cardiovascular comorbidity. Of the total
      patients 554 (51.0%) died, and 711 (65.5%) were hospitalized. Using an intent-to
      treat approach, CT-betaB was associated with a lower risk of mortality (all
      cause: RR [CI 95%] 0.37 [0.21 to 0.50], and cardiovascular: 0.31 [0.18 to 0.45]),
      and a lower age- and sex-adjusted hospitalization rate (per 100 persons/year),
      13.6 vs. 19.2, (P<0.001 in all cases), even after adjustment for the propensity
      to take beta-blockers, or other medications, comorbidities, and other potential
      confounders. CONCLUSIONS: In this observational study, commencing treatment with
      the beta-blockers bisoprolol or carvedilol is associated with a reduced mortality
      and morbidity of patients with newly diagnosed heart failure with preserved
      systolic function.

PMID- 19573939
TI  - Nicorandil ameliorates impulse conduction disturbances during ischemia in
      isolated arterially perfused canine atria.
AB  - BACKGROUND: Nicorandil has protective effects on the ischemic atrial myocardium.
      However, effects of nicorandil on ischemia-induced impulse conduction
      disturbances are still uncertain. METHODS: Optical action potentials were
      recorded from 256 sites of the left atrium in isolated arterially perfused canine
      atria during the left atrial ischemia. Constant pacing (BCL = 350 ms) from the
      left superior pulmonary vein (LSPV) and the posterior left atrium (PLA) was
      performed, and local conduction velocity (CV) was calculated at the LSPV-left
      atrial (LA) junction and the right inferior PV (RIPV)-LA junction. Impulse
      conduction failure was elucidated within the optical mapping field during sinus
      rhythm. RESULTS: In the control, ischemia slowed the local CV at both regions
      regardless of the pacing site, and impulse conduction failure occurred within the
      mapping field during sinus rhythm. Nicorandil suppressed the ischemic conduction
      slowing at both regions and prevented the conduction failure. Nicorandil also
      reduced the dispersion of local CV during ischemia. HMR1098, a blocker of cardiac
      sarcolemmal K(ATP) channels abolished suppression of the ischemic conduction
      slowing by nicorandil at the RIPV-LA junction but not at the LSPV-LA junction and
      induced the conduction failure. 5-HD, a blocker of mitochondrial K(ATP) channels
      also abolished it at both regions and induced the conduction failure. 5-HD
      abolished the decreased dispersion of local CV by nicorandil, and HMR1098 further
      increased the dispersion of local CV compared with the control. CONCLUSIONS:
      These results indicate that nicorandil suppresses ischemia-induced impulse
      conduction disturbances by its action on both the mitochondrial and sarcolemmal
      K(ATP) channels.

PMID- 19573940
TI  - Left anterior descending artery length and coronary atherosclerosis in apical
      ballooning syndrome (Takotsubo/stress induced cardiomyopathy).
AB  - BACKGROUND: A proposed etiology of apical ballooning syndrome (ABS) is a
      spontaneously aborted anterior myocardial infarction (MI) in patients with a long
      "wrap around" left anterior descending artery (LAD) rather than it being a unique
      cardiomyopathy. The aim of this study was to evaluate whether patients with ABS
      have a higher frequency of "wrap around" LAD. METHODS: A retrospective analysis
      of the coronary anatomy and presence of coronary artery disease (CAD) by
      angiography was performed among 97 ABS patients, and compared to a matched
      control group with anterior ST-elevation MI. LAD length was graded: type 1--does
      not supply the left ventricular (LV) apex, type 2--the LAD and right coronary
      both supply the apex, type 3--supplies the entire apex, and type 4--supplies the
      apex and >25% of the inferior wall (wrap around). RESULTS: ABS patients had lower
      ejection fractions at presentation (41% +/- 14% vs 47% +/- 13%, p=0.001). There
      was no difference in the frequency of the 4 types of LAD between ABS (7%, 11%,
      55%, 27%) and controls (3%, 13%, 51%, 33%), p=0.45. In ABS, there was no
      difference in the mean LV ejection fraction (32.7%, 38.8%, 42.9%, 41.1%,
      respectively, p=0.39), or wall motion score index at presentation in the 4 LAD
      groups. The prevalence of angiographic CAD in ABS was 84%. CONCLUSIONS: ABS
      patients do not have a higher frequency of "wrap around" LAD. This fact, together
      with a greater magnitude of LV dysfunction at presentation, supports that
      cardiomyopathy is not due to spontaneously aborted anterior MI.

PMID- 19573941
TI  - Pattern of blood pressure in Australian adults: results from a national blood
      pressure screening day of 13,825 adults.
AB  - BACKGROUND: Recent national data of cardiovascular disease (CVD) risk factors in
      Australia are limited. Therefore this study sought to gain a contemporary
      snapshot of the blood pressure (BP) profile of Australian adults. METHODS: We
      established 100 metropolitan and regional screening sites. Using a standardized
      protocol and the same automated, validated BP monitor, Registered Nurses recorded
      the BP and other risk factors for CVD of self-selected volunteers on a single
      day. RESULTS: A total of 13,825 subjects (55% female, aged 48+/-16 years) were
      assessed. Mean systolic and diastolic BP was 131+/-18 and 79+/-12 mm Hg. Overall,
      34% had an elevated BP while 10% being treated for hypertension (HT) were
      normotensive (combined total 44%). Elevated BP was more common in older
      individuals, men (42% versus 27% of women), regional dwelling residents (40%
      versus 32% of metropolitan) and people from lower socio-economic backgrounds (39%
      versus 30% of higher). Overall, 50% of subjects with a history of HT had elevated
      BP compared to 30% without a history of HT. Adjusting for age and sex, elevated
      BP was independently associated with obesity (OR: 1.77, 95% CI 1.52-2.06),
      regional location (OR: 1.32, 95% CI 1.19-1.45) and modifiable risk factors (OR:
      1.28, 95% CI 1.21-1.35); those being treated for CVD or diabetes are less likely
      to have high BP. CONCLUSIONS: In the largest study of its kind in Australia, the
      findings highlight the need for continued vigilance to detect, monitor and
      prevent elevated BP within an ageing population in whom metabolic disorders are
      becoming more frequent.

PMID- 19573942
TI  - Management- and housing-related risk factors of respiratory disorders in non
      weaned French Charolais calves.
AB  - Our aim was to determine at calf-batch level the management- and housing-related
      risk factors of respiratory disorders in non-weaned Charolais calves. Farmers
      recorded cases according to the definition provided i.e. the association of at
      least one respiratory sign and, in the same calf or another calf of the same
      batch, at least one general sign on the same day or the day before. During farm
      visits, quality of farmers' records was checked and questionnaires were applied
      to gather farm and herd characteristics and to describe farming practices and
      housing facilities. Data were suitable for analysis for 172 batches where no
      metaphylactic treatment was implemented. Batches had great disparity in incidence
      of respiratory disorders. In the 120 batches with at least one case, the
      quartiles of incidence rate were, respectively, 0.95, 2.15 and 3.59 cases per
      1000 calf-days at-risk. For risk-factor analysis, the statistical unit was the
      calf-batch located in a given batch. We used a ZINB model because (i) there was
      significant overdispersion of incidence rates of respiratory disorders
      (overdispersion test statistic of O=1049 (P<0.001)), (ii) probability was high
      that a two-group modelling process existed (Vuong statistic of V=2.44 (P=0.0073))
      and (iii) the ZINB model fit significantly better than the ZIP model (likelihood
      ratio statistic of 340.14 (P<0.001)). The risk was higher in open-fronted barns
      or in open barns compared to closed ones (incidence-rate ratios (IRRs): 1.9 and
      1.8), in barns where no annual disinfection was implemented (IRR: 1.5) and in
      part slope with straw/part scraped and in part straw-bedded/part scraped barns
      compared to completely straw-bedded barns (IRRs: 1.9 and 1.6). Larger calf
      batches were more at-risk than smaller batches (OR for the effect of an increase
      of 10 calves on the probability of a 0 count: 0.5).

PMID- 19573943
TI  - Methodological quality and completeness of reporting in clinical trials conducted
      in livestock species.
AB  - Randomized controlled trials (RCTs) are the gold standard for evaluating efficacy
      of treatments under real world conditions and, as such, it is important that they
      are conducted with methodological rigour to prevent biased results. Many medical
      journals have adopted a standard checklist for reporting of RCTs, the CONSORT
      statement. The objective of this study was to evaluate clinical trials in
      livestock populations to assess methodological quality and completeness of
      reporting and to investigate the association between these criteria and treatment
      effects. A total of 100 clinical trials published between 2006 and 2008 in the
      English language were randomly selected. For each trial, 2 reviewers
      independently completed a checklist based on the CONSORT statement and a
      different 2 reviewers completed a standard template describing the outcomes used
      and the statistical significance of all reported treatment effects. Disagreements
      among reviewers were resolved by consensus. The results showed that there were
      substantive deficiencies in the reporting of many of trial features, both related
      to methodological quality and completeness of reporting. Details on key features
      such as randomization, double blinding, and the number of subjects lost to follow
      up were reported in only 67, 4, and 62% of trials, respectively. Reporting of
      random allocation to treatment group was associated with a lower proportion of
      positive treatments effects within trials, as was reporting of
      inclusion/exclusion criteria for study subjects, details on the intervention,
      animal signalment, significance tests of baseline differences for at least one
      variable, and the methods used to measure all outcomes. The results suggest that
      there are deficiencies in the current reporting of important features of RCTs
      conducted in livestock species and that these deficiencies may be associated with
      biased treatment effects. The creation and adoption of standards for trial
      reporting in livestock could aid authors, reviewers, and editors in ensuring that
      necessary trial details are reported in all published trials.

PMID- 19573944
TI  - Advances in product release strategies and impact on bioprocess design.
AB  - Intracellular products such as recombinant insulin, which are typically produced
      in microbial host cells, demand a product release step to remove them from the
      cell. How this is performed determines the quantity of released contaminants, the
      particle size distribution of cell debris and the physical properties of the
      resultant process stream, which all impact on the performance of the downstream
      operations. Thus, achieving selective release of the desired product is crucial
      for improving the process economics. Advances in upstream processing (the
      bioreactor phase) have been successful in achieving high product titres, and
      downstream costs now typically dominate the overall manufacturing costs. Here, we
      review and discuss the selective release of products as a possible means of
      improving the efficiency of downstream processing.

PMID- 19573945
TI  - Plasma markers of cholesterol homeostasis in metabolic syndrome subjects with or
      without type-2 diabetes.
AB  - AIMS: We investigated the associations between indices of cholesterol metabolism
      and features of the metabolic syndrome (MS) in the presence and absence of type-2
      diabetes (T2DM). METHODS: Men with the MS (N=140) and 10 age- and sex-matched
      controls were recruited. Plasma lathosterol and campesterol were measured by gas
      chromatography-mass spectrometry, and their ratios to total cholesterol were used
      to estimate cholesterol metabolism. RESULTS: Compared with healthy controls, MS
      subjects had significantly higher lathosterol:cholesterol and lower
      campesterol:cholesterol ratios (p<0.05). In the MS subjects without T2DM (N=82),
      campesterol:cholesterol ratio was positively associated with age and negatively
      associated with plasma triglyceride and insulin concentrations, while in MS
      subjects with T2DM (N=58), the ratio was positively associated with age and
      adiponectin concentration, and negatively associated with BMI and insulin. Age
      and fasting insulin were independent predictors of campesterol:cholesterol ratio
      in MS subjects with T2DM. There was a significant negative association between
      plasma lathosterol:cholesterol with campesterol:cholesterol ratio (r=-0.436,
      p=0.014) in MS subjects without T2DM but not in MS subjects with T2DM.
      CONCLUSIONS: Cholesterol absorption efficiency was lower and cholesterol
      synthesis higher in MS subjects with or without T2DM compared with healthy
      individuals. Moreover, the reciprocal relationship between cholesterol synthesis
      and cholesterol absorption is lost in the presence of diabetes.

PMID- 19573946
TI  - Does noise reduction matter for curve fitting in growth curve models?
AB  - In this paper, we discuss the efficiency of noise reduction for curve fitting in
      nonlinear growth curve models. We use singular spectrum analysis as a nonlinear
      nonparametric denoising method. A set of longitudinal measurements is used in
      considering the performance of the method. We also use artificially generated
      data sets with and without noise for the purpose of validation of the results
      obtained in this study. The results show that noise reduction is important for
      curve fitting in growth curve models and also, that the singular spectrum
      analysis technique can be used as a powerful tool for noise reduction in
      longitudinal measurements.

PMID- 19573947
TI  - Enhancement of taxane production in hairy root culture of Taxus x media var.
      Hicksii.
AB  - This study assessed the effect of two precursors (l-phenylalanine and p-amino
      benzoic acid) used alone or in combination with methyl jasmonate, on the growth
      and accumulation of paclitaxel, baccatin III and 10-deacetylbaccatin III in hairy
      root cultures of Taxus x media var. Hicksii. The greatest increase in dry biomass
      was observed after 4 weeks of culturing hairy roots in medium supplemented with
      1microM of l-phenylalanine (6.2gL(-1)). Addition of 1microM of l-phenylalanine to
      the medium also resulted in the greatest 10-deacetylbaccatin III accumulation
      (422.7microg L(-1)), which was not detected in the untreated control culture.
      Supplementation with 100microM of l-phenylalanine together with 100microM of
      methyl jasmonate resulted in the enhancement of paclitaxel production from
      40.3microg L(-1) (control untreated culture) to 568.2microg L(-1), the highest
      paclitaxel content detected in the study. The effect of p-amino benzoic acid on
      taxane production was less pronounced, and the highest yield of paclitaxel
      (221.8microg L(-1)) was observed when the medium was supplemented with 100microM
      of the precursor in combination with methyl jasmonate. Baccatin III was not
      detected under the conditions used in this experiment and the investigated
      taxanes were not excreted into the medium.

PMID- 19573948
TI  - Advancing the science of emergency department crowding: measurement and
      solutions.

PMID- 19573949
TI  - Interruptions in cardiopulmonary resuscitation from paramedic endotracheal
      intubation.
AB  - STUDY OBJECTIVE: Emergency cardiac care guidelines emphasize treatment of
      cardiopulmonary arrest with continuous uninterrupted cardiopulmonary
      resuscitation (CPR) chest compressions. Paramedics in the United States perform
      endotracheal intubation on nearly all victims of out-of-hospital cardiopulmonary
      arrest. We quantified the frequency and duration of CPR chest compression
      interruptions associated with paramedic endotracheal intubation efforts during
      out-of-hospital cardiopulmonary arrest. METHODS: We studied adult out-of-hospital
      cardiopulmonary arrest treated by an urban and a rural emergency medical services
      agency from the Resuscitation Outcomes Consortium during November 2006 to June
      2007. Cardiac monitors with compression sensors continuously recorded rescuer CPR
      chest compressions. A digital audio channel recorded all resuscitation events. We
      identified CPR interruptions related to endotracheal intubation efforts,
      including airway suctioning, laryngoscopy, endotracheal tube placement,
      confirmation and adjustment, securing the tube in place, bag-valve-mask
      ventilation between intubation attempts, and alternate airway insertion. We
      identified the number and duration of CPR interruptions associated with
      endotracheal intubation efforts. RESULTS: We included 100 of 182 out-of-hospital
      cardiopulmonary arrests in the analysis. The median number of endotracheal
      intubation-associated CPR interruption was 2 (interquartile range [IQR] 1 to 3;
      range 1 to 9). The median duration of the first endotracheal intubation
      associated CPR interruption was 46.5 seconds (IQR 23.5 to 73 seconds; range 7 to
      221 seconds); almost one third exceeded 1 minute. The median total duration of
      all endotracheal intubation-associated CPR interruptions was 109.5 seconds (IQR
      54 to 198 seconds; range 13 to 446 seconds); one fourth exceeded 3 minutes.
      Endotracheal intubation-associated CPR pauses composed approximately 22.8% (IQR
      12.6-36.5%; range 1.0% to 93.4%) of all CPR interruptions. CONCLUSION: In this
      series, paramedic out-of-hospital endotracheal intubation efforts were associated
      with multiple and prolonged CPR interruptions.

PMID- 19573950
TI  - GSK3beta polymorphisms, MAPT H1 haplotype and Parkinson's disease in a Greek
      cohort.
AB  - To determine whether polymorphisms in the microtubule-associated protein tau
      (MAPT) and/or glycogen synthase kinase-3beta (GSK3beta) genes underpin
      susceptibility to Parkinson's disease (PD), we conducted a case-control
      association study in a Greek cohort of 196 PD cases and 163 healthy controls. In
      our study, the MAPT H1 haplotype was found to be significantly associated with
      PD, no association was detected between the intronic rs6438552 (-157 T/C)
      GSK3beta polymorphism and PD, whereas the C/C genotype of the promoter rs334558 (
      50 T/C) GSK3beta polymorphism was found to exert a protective role. The C/C
      genotype of the rs334558 GSK3beta polymorphism was also found to have an
      additional protective role in our MAPT H1/H1 PD subgroup. Haplotype analysis
      revealed that, the T-T haplotype of both GSK3beta polymorphisms was over
      represented in PD patients compared to controls, and this association was
      independent of MAPT H1 haplotype.

PMID- 19573951
TI  - [Differences in momentum development when standing up from a chair between
      elderly with and without frequent falls history].
AB  - INTRODUCTION: The momentum of the upper body (UB) during transfer sit-to-stand
      (STS) could be sensitive to the deterioration of dynamic postural control, and
      also the risk of falls. The aim of this study is to quantify the differences in
      the momentum development on UB during the STS in a sample of fall and no-fall
      elderly subjects. MATERIAL AND MEHODS: The sample consisted of twenty three
      voluntary elderly subjects (n=23), six elderly adults with antecedents of
      frequent falls (more than two within a year period) and seventeen without
      histories of frequent falls. Through a motion analysis system we registered the
      kinematics of UB during STS, from which we calculated the momentum of UB. The
      determined analysis variables were: the maximum values of the vertical (P(V)M)
      and horizontal (P(H)M) lineal momenta, the minimum (L(Max)) and maximum (L(Min))
      values of the angular momentum and maximum trunk flexion (thetaM(UB)). RESULTS:
      No difference was observed in P(H)M, L(Max) and L(Min) (P>0.05) between both
      groups. However, a significant difference was found for the variable P(V)M
      (P=0.03) and thetaM(UB) (P=0.03) between both groups. CONCLUSIONS: We can
      conclude that, for the sample studied, the frequent fall condition relates to a
      smaller capacity to develop vertical momentum and increase flexion of the upper
      body.

PMID- 19573952
TI  - [Caloric restriction and aging in humans].

PMID- 19573953
TI  - [Efficiency of acute geriatric units in Spain hospitals].
AB  - OBJECTIVES: To review published data from Spanish hospitals in which comparisons
      had been made between the mean length of stay in patients admitted to acute
      geriatric units (AGU) and those admitted to other departments using the diagnosis
      related groups (DRG) classification system and to describe our own experience.
      MATERIAL AND METHODS: The Spanish reports collected in a previous systematic
      review were reviewed. The case mix of our hospital was added by analyzing
      episodes in patients older than 74 years old discharged during a 24-month period
      and included in the most frequent DRGs. The length of stay in patients admitted
      to the AGU was compared with that in the remaining medical departments in the
      hospital and with the standard average stay in the corresponding autonomous
      region. RESULTS: Data were obtained from five Spanish general hospitals. The
      comparison revealed that the mean length of stay in the AGU was 8-19% shorter
      than that of similar patients in the other medical departments of the same
      hospitals. In one hospital, the reduction in the mean length of stay was 21% in
      patients older than 80 years. In three of the four hospitals where comparisons
      with the standard were performed, the mean length of stay in the AGU was lower
      for most of the DRGs, showing reductions of 7-9%. CONCLUSIONS: These results
      allow us to conclude that, based on the commonly used patient classification and
      coding system, Spanish AGUs are more efficient than the remaining medical
      services in the acute hospitalization of elderly patients in our setting.

PMID- 19573954
TI  - [Optimal cut-point of salivary cotinine concentration to discriminate smoking
      status in the adult population in Barcelona].
AB  - OBJECTIVE: To assess the optimal cut-point for salivary cotinine concentration to
      identify smoking status in the adult population of Barcelona. METHODS: We
      performed a cross-sectional study of a representative sample (n=1,117) of the
      adult population (>16 years) in Barcelona (2004-2005). This study gathered
      information on active and passive smoking by means of a questionnaire and a
      saliva sample for cotinine determination. We analyzed sensitivity and specificity
      according to sex, age, smoking status (daily and occasional), and exposure to
      second-hand smoke at home. ROC curves and the area under the curve were
      calculated. RESULTS: The prevalence of smokers (daily and occasional) was 27.8%
      (95% CI: 25.2-30.4%). The optimal cut-point to discriminate smoking status was
      9.2 ng/ml (sensitivity=88.7% and specificity=89.0%). The area under the ROC curve
      was 0.952. The optimal cut-point was 12.2 ng/ml in men and 7.6 ng/ml in women.
      The optimal cut-point was higher at ages with a greater prevalence of smoking.
      Daily smokers had a higher cut-point than occasional smokers. CONCLUSIONS: The
      optimal cut-point to discriminate smoking status in the adult population is 9.2
      ng/ml, with sensitivities and specificities around 90%. The cut-point was higher
      in men and in younger people. The cut-point increases with higher prevalence of
      daily smokers.

PMID- 19573955
TI  - [The tobacco industry and smoking promotion among minors and youths: an
      international review].
AB  - OBJECTIVES: To compile scientific documentation of the historic interest of the
      tobacco industry in minors and youths. METHODS: We performed a literature review
      of electronic scientific databases and an electronic search of technical reports
      and scientific articles published after 1999. RESULTS: Thirteen technical reports
      and 30 articles in international scientific journals and other publications were
      retrieved and summarized. Most reports and articles focused on advertisements and
      marketing. CONCLUSIONS: This study compiled evidence of the interest of the
      tobacco industry in promoting tobacco use among minors and youths globally, as
      well as in interfering with tobacco control policies that prevent tobacco smoking
      initiation among youths.

PMID- 19573956
TI  - Electronic learning and constructivism: a model for nursing education.
AB  - Nurse educators are challenged to teach nursing students to become competent
      professionals, who have both in-depth knowledge and decision-making skills. The
      use of electronic learning methods has been found to facilitate the teaching
      learning process in nursing education. Although learning theories are
      acknowledged as useful guides to design strategies and activities of learning,
      integration of these theories into technology-based courses appears limited.
      Constructivism is a theoretical paradigm that could prove to be effective in
      guiding the design of electronic learning experiences for the purpose of
      providing positive outcomes, such as the acquisition of knowledge and decision
      making skills. Therefore, the purposes of this paper are to: describe electronic
      learning, present a brief overview of what is known about the outcomes of
      electronic learning, discuss constructivism theory, present a model for
      electronic learning using constructivism, and describe educators' roles
      emphasizing the utilization of the model in developing electronic learning
      experiences in nursing education.

PMID- 19573957
TI  - Decreased food intake is a risk factor for mortality in hospitalised patients:
      the NutritionDay survey 2006.
AB  - BACKGROUND & AIMS: Malnutrition is a known risk factor for the development of
      complications in hospitalised patients. We determined whether eating only
      fractions of the meals served is an independent risk factor for mortality.
      METHODS: The NutritionDay is a multinational one-day cross-sectional survey of
      nutritional factors and food intake in 16,290 adult hospitalised patients on
      January 19th 2006. The effect of food intake and nutritional factors on death in
      hospital within 30 days was assessed in a competing risk analysis. RESULTS: More
      than half of the patients did not eat their full meal provided by the hospital.
      Decreased food intake on NutritionDay or during the previous week was associated
      with an increased risk of dying, even after adjustment for various patient and
      disease related factors. Adjusted hazard ratio for dying when eating about a
      quarter of the meal on NutritionDay was 2.10 (1.53-2.89); when eating nothing
      3.02 (2.11-4.32). More than half of the patients who ate less than a quarter of
      their meal did not receive artificial nutrition support. Only 25% patients eating
      nothing at lunch receive artificial nutrition support. CONCLUSION: Many
      hospitalised patients in European hospitals eat less food than provided as
      regular meal. This decreased food intake represents an independent risk factor
      for hospital mortality.

PMID- 19573958
TI  - Prevalence of undernutrition on admission to Swiss hospitals.
AB  - BACKGROUND & AIMS: According to the literature, undernutrition is prevalent in 20
      60% of patients on hospital admission. The differences in the rate of
      undernutrition arise from different diagnostic tools used in the studies. We
      aimed to investigate the prevalence of undernutrition in Swiss hospitals using a
      standardized screening tool. METHODS: All patients admitted to the departments of
      internal medicine of 7 Swiss hospitals were screened at entry for nutritional
      status using the Nutrition Risk Screening 2002 score. Patients with a score of 3
      or more, which denotes severe undernutrition or patient "at risk" for
      undernutrition were analyzed. RESULTS: Between May 2003 and April 2006 32,837
      patients were included in the study. 5978 (18.2%) had a score of 3 or more and
      were classified as severely undernourished or at high risk for undernutrition
      (age<45 y: 8%; 45-64 y: 11%; 65-84 y: 22%; >85 y: 28%). A nutritional
      intervention was made in 4175 patients (12.7%). CONCLUSIONS: Nearly one in five
      patients was severely undernourished or "at risk" for undernutrition.
      Undernutrition was directly related to age. Patients with a clear indication for
      nutrition therapy, as suggested by the formal screening procedure, obtained
      nutritional intervention in 70%.

PMID- 19573959
TI  - Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?
AB  - BACKGROUND & AIMS: NF-kappaB may promote carcinogenesis by altering cell cycle,
      inflammatory responses and apoptosis-related gene expression, though cell
      mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans.
      This study in patients with CRC aimed to explore potential interactions between
      the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and
      tumour histological aggressiveness. METHODS: Usual diet was assessed by diet
      history; nutrient composition was determined by DIETPLAN software. Histologically
      classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding
      mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF
      kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL
      assay. RESULTS: NF-kappaB expression and apoptosis were higher in tumours
      (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake
      terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids
      and alcohol were associated with higher NF-kappaB, apoptosis and histological
      aggressiveness (p<0.01); the opposite tissue characteristics were associated with
      highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids,
      isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3
      fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006)
      and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower
      n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB
      (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002).
      CONCLUSIONS: NF-kappaB expression and apoptosis increased from adenoma to poorly
      differentiated adenocarcinoma. This degenerative transition, recognized as key in
      carcinogenesis, appear to have been influenced by a diet promoting a pro
      inflammatory milieu that can trigger NF-kappaB.

PMID- 19573960
TI  - Influence of an eicosapentaenoic and docosahexaenoic acid-enriched enteral
      nutrition formula on plasma fatty acid composition and biomarkers of insulin
      resistance in the elderly.
AB  - BACKGROUND & AIMS: n-3 Polyunsaturated fatty acids may improve cardiovascular
      outcomes in elderly. The aim of this study was to determine the effect of feeding
      elderly patients exclusively with an n-3 polyunsaturated fatty acid-enriched diet
      specifically designed for enteral nutrition for 6 months, evaluating
      modifications in plasma fatty acid profile and some biomarkers of insulin
      resistance (IR). METHODS: Thirty-two patients >65 years were fed a new enteral
      formula (T-Diet Plus) containing 75 mg/l of eicosapentaenoic acid (EPA) and 35
      mg/l of docosahexaenoic acid (DHA) and 33 were fed an enteral diet intended for
      elderly (Jevity). Blood samples were drawn at the beginning and after 3 and 6
      months of feeding. Plasma lipids, total plasma and lipid fraction fatty acid
      profiles, and some IR-associated adipokines were analysed. RESULTS: Feeding on T
      Diet Plus allowed EPA and DHA incorporation into plasma lipids and normalised
      blood triacylglycerols (TAG) levels after 3 months without major changes in IR,
      leptin and adiponectin. CONCLUSIONS: Feeding the elderly exclusively with an
      enteral formula enriched with EPA and DHA improves their plasma lipid fatty acid
      profile and lowers TAG, a well known cardiovascular risk biomarker, without
      affecting IR.

PMID- 19573961
TI  - Food chain transfer of cadmium and lead to cattle in a lead-zinc smelter in
      Guizhou, China.
AB  - Cadmium (Cd) and Lead (Pb) are environmental pollutants. Environmental samples
      and bovine tissues were collected from the areas around a lead-zinc smelter in
      Guizhou, China for Cd, Pb, zinc (Zn) and copper (Cu) analysis. Cd in soil (10
      mg/kg) and feed (6.6 mg/kg) from the polluted areas was 10 times higher than the
      Chinese Standards, resulting in higher Cd in bovine kidney (38 mg/kg) and liver
      (2.5 mg/kg). Pb in feed (132 mg/kg) from the polluted area was much higher than
      unpolluted areas, causing higher Pb levels in bovine tissues. Environmental Zn
      was elevated, but bovine tissue Zn was normal. Cu in bovine liver decreased with
      increased Cd and Pb. Metals in drinking water and in bovine muscle were within
      the Standard range. Thus, in the areas of this lead-zinc smelter, the environment
      has been contaminated with Cd and Pb, which has been transferred to cattle
      through the food chain.

PMID- 19573962
TI  - Nitrous oxide supersaturation at the liquid/air interface of animal waste.
AB  - Concentrated animal feeding operations around the globe generate large amounts of
      nitrous oxide (N(2)O) in the surrounding atmosphere. Liquid animal waste systems
      have received little attention with respect to N(2)O emissions. We hypothesized
      that the solution chemistry of animal waste aqueous suspensions would promote
      conditions that lead to N(2)O supersaturation at the liquid/air interface. The
      concentration of dissolved N(2)O in poultry litter (PL) aqueous suspensions at 25
      degrees C was 0.36 microg N(2)O mL(-1), at least an order of magnitude greater
      than that measured in water in equilibrium with ambient air, suggesting N(2)O
      supersaturation. There was a nonlinear increase in the N(2)O Henry constants of
      PL from 2810 atm/mole fraction at 35 degrees C to 17 300 atm/mole fraction at 41
      degrees C. The extremely high N(2)O Henry constants were partially ascribed to
      N(2)O complexation with aromatic moieties. Complexed N(2)O structures were
      unstable at temperatures > 35 degrees C, supplying the headspace with additional
      free N(2)O concentrations.

PMID- 19573963
TI  - An intradialysis diagnostic test for restless legs syndrome: a pilot study.
AB  - BACKGROUND: Restless legs syndrome (RLS) is common in dialysis patients, but a
      simple diagnostic test is not available. STUDY DESIGN: Diagnostic test study.
      SETTING & PARTICIPANTS: 32 patients with RLS and 29 patients without RLS in 2
      dialysis centers. INDEX TEST: The suggested immobilization test (SIT) was
      performed during dialysis for at least 30 minutes, and periodic limb movements
      (PLMs) were assessed by means of electromyography of the anterior tibialis
      muscles using a Holter monitor as an electromyographic monitoring device. We also
      assessed changes in number of leg movements on the 30-minute SIT (SIT-PLM) after
      4 weeks of treatment with the dopamine agonist pergolide. REFERENCE TEST OR
      OUTCOME: Clinical review by a neurologist, International RLS Rating Scale
      (IRLSRS) score, and changes in IRLSRS score after pergolide treatment. RESULTS:
      PLMs on the 30-minute SIT during dialysis were identified in 20 of 32 patients
      with RLS and 3 of 29 control participants. Sensitivity and specificity of PLMs on
      the 30-minute SIT during dialysis for RLS diagnosis were 63% and 90%,
      respectively. SIT-PLM correlated with IRLSRS total score at diagnosis (r = 0.53;
      P = 0.03), suggesting that SIT-PLM measures the general severity of RLS in uremic
      patients. Treatment with the dopamine agonist pergolide significantly reduced the
      IRLSRS total score (from a mean of 24.9 +/- 9.1 [SD] to 9.5 +/- 6.8; P < 0.01)
      and SIT-PLM (from 41.9 +/- 24.2 to 11.3 +/- 12.3; P < 0.01), but correlation
      between changes in SIT-PLM and those in IRLSRS score was not significant (r =
      0.27; P = 0.3). LIMITATIONS: Poor correlation may be caused by the small sample
      size. Time available for the SIT was limited because of the patient's condition
      during dialysis. Time of day during SIT, mental-alerting activities during SIT,
      or hemodialysis therapy itself may influence the severity of PLMs. CONCLUSIONS: A
      Holter-monitored SIT during dialysis is a valid method for the diagnosis of RLS
      and to evaluate the effect of treatment with pergolide in uremic patients.

PMID- 19573964
TI  - Contextualizing the neurobiology of conduct disorder in an emotion dysregulation
      framework.
AB  - Conduct disorder (CD) represents the most common childhood psychiatric disorder
      found in community and mental health clinics. This paper provides a comprehensive
      review of the neurobiology of CD; specifically, neurological and neurochemical
      correlates. Converging evidence suggests that neurological profiles of
      individuals with CD, compared to peers, are characterized by reduced P300 brain
      wave amplitude, deactivation of the anterior cingulated cortex and reduced
      activation in the left amygdala in response to negative stimuli, and reduced
      right temporal lobe volume. The neurochemical profiles of individuals with CD are
      characterized by reduced serotonin and cortisol levels (i.e., decreased HPA axis
      function), as well as attenuated autonomic nervous system functioning. Popular
      theoretical frameworks cited within the CD literature are limited in their
      ability to explain and consolidate the neurological and neurochemical findings.
      We believe that emotion dysregulation theory, though not often used within CD
      research, may provide the most comprehensive and inclusive framework for
      understanding neurobiological aspects of this disorder. Limitations within the
      literature, future directions for research, and implications of the findings will
      be discussed.

PMID- 19573965
TI  - Gender and access to HIV testing and antiretroviral treatments in Thailand: why
      do women have more and earlier access?
AB  - In the recent scale-up of antiretroviral treatment, gender differences in access
      to treatment have been reported. In Thailand, as the HIV epidemic became more
      generalised, there has been a shift from men being disproportionately affected to
      increased vulnerability of women. In 2007, the Living with Antiretrovirals (LIWA
      ANRS 12141) study investigated the gender distribution of all adult patients
      receiving antiretroviral therapy (N=513 patients) in four community hospitals in
      northern Thailand and factors influencing the disparities observed. From this
      retrospective life-event history survey, we found that proportionately more women
      (53%) were receiving antiretroviral therapy than men, an unexpected result for a
      country with a higher proportion of infections among men. They were more likely
      to initiate treatment within one year of diagnosis and were at a more advanced
      stage of the disease compared to women. This gender distribution is partly
      explained by the evolving dynamics of the HIV epidemic, initial prioritization of
      mothers for treatment and earlier access to HIV testing for women. These issues
      are also entangled with gender differences in the reasons and timing to HIV
      testing at the individual level. This study found that the majority of men
      underwent HIV testing for health reasons while the majority of women were tested
      following family events such as a spouse/child death or during pregnancy. Further
      qualitative research on gender specific barriers to HIV testing and care, such as
      perceived low risk of infection, poor access to medical care, lack of social
      support, actual or anticipated HIV/AIDS-related stigma would provide greater
      insight. In the meantime, urgent efforts are needed to increase access to
      voluntary counselling and testing inside and outside the family setting with
      targeted interventions for men.

PMID- 19573966
TI  - Visual epidemiology: photographs as tools for probing street-level etiologies.
AB  - Epidemiologists and social scientists agree that place shapes health. But the
      model of "risk factor" epidemiology faces limits in explaining how neighborhoods,
      as complex systems, produce health or disease. This paper describes how visual
      methods can advance epidemiological inquiry. Drawing from the work of The Health
      of Philadelphia Photo-documentation Project (HOPPP), this paper asks the
      following question: how can visual methods inform the work of epidemiologists?
      The project was conducted in three contiguous neighborhoods that represent a
      steep socioeconomic gradient. Photographs served as a stimulus for probing the
      sources of health variation across neighborhoods. The project incorporated three
      visual data sources: 1) "outsider perspective" images gathered systematically by
      staff photographers on randomly sampled blocks; 2) "insider perspective" images
      taken by adult residents during their daily routines; and 3) collaborative images
      taken by staff photographers in partnership with local participants. During in
      depth interviews, these photographs served as prompts to elicit residents' health
      concerns and beliefs regarding urban environmental causes of good and poor health
      ("street-level etiologies"). We found that visual methods generated etiologic
      insights regarding the production of urban health and illness. Photographs
      enabled systematic observation of urban neighborhoods by the research team;
      engaged urban residents as active agents in the search for the underlying causes
      of urban health disparities; and created a social bridge between researchers and
      urban residents.

PMID- 19573967
TI  - Comparing hospital costs: what is gained by accounting for more than a case-mix
      index?
AB  - We explore what effect controlling for various patient characteristics beyond a
      case-mix index (DRG) has on inferences drawn about the relative cost performance
      of hospital departments. We estimate fixed effect cost models in which 3754
      patients are clustered within six Danish vascular departments. We compare a basic
      model including a DRG index only with models also including age and gender,
      health related characteristics, such as smoking status, diabetes, and American
      Society of Anesthesiogists score (ASA-score), and socioeconomic characteristics
      such as income, employment and whether the patient lives alone. We find that the
      DRG index is a robust and important explanatory factor and adding other routinely
      collected characteristics such as age and gender and other health related or
      socioeconomic characteristics do not seem to alter the results significantly. The
      results are more sensitive to choice of functional form, i.e. in particular to
      whether costs are log transformed. Our results suggest that the routinely
      collected characteristics such as DRG index, age and gender are sufficient when
      drawing inferences about relative cost performance. Adding health related or
      socioeconomic patient characteristics only slightly improves our model in terms
      of explanatory power but not when drawing inferences about relative performance.
      The results are, however, sensitive to whether costs are log transformed.

PMID- 19573968
TI  - The different effects of vertical social capital and horizontal social capital on
      dental status: a multilevel analysis.
AB  - Few studies distinguish between the effects of different forms of social capital
      on health and of those that do none use physical indicators of health as an
      outcome variable. The objective of this study was to determine whether vertical
      and horizontal social capital had different associations with dental status of
      elderly Japanese. In this cross-sectional study, self-administered questionnaires
      were mailed to elderly individuals living in 25 Japanese communities in 2003.
      Data from 5560 respondents (49.9%, 72.9+/-6.0 years) included information on
      social capital, numbers of remaining teeth, health behaviors, physical and mental
      health, and socioeconomic status. Vertical social capital was defined as
      participating in groups which encouraged hierarchical relations and horizontal
      social capital as participating in groups of equals. A multilevel logistic
      regression analysis was conducted to assess the association between social
      capital and number of remaining teeth (< or = 19 teeth or > or = 20 teeth). The
      prevalence of people with 19 or less teeth was 70.7%. Univariate analysis showed
      significant beneficial associations between individual horizontal social capital
      and number of remaining teeth. After adjusting for individual- and community
      level covariates in multilevel analysis, community-level horizontal social
      capital still showed beneficial association. Compared to respondents living in
      highest horizontal social capital areas, those living in lowest horizontal social
      capital areas had a 1.25 times higher odds ratio for having 19 or less teeth.
      Individual-level horizontal social capital also showed beneficial effects on
      number of remaining teeth. Community- and individual-level vertical social
      capital did not show significant associations with dental status. The results
      suggest that horizontal social capital, not vertical social capital, has
      beneficial effects on numbers of remaining teeth in older Japanese adults.

PMID- 19573969
TI  - Economic valuation of informal care in Asia: a case study of care for disabled
      stroke survivors in Thailand.
AB  - This study values informal care for disabled stroke survivors in Thailand. It
      applies the conventional recommended opportunity cost method to value informal
      care in monetary terms. Data were collected by means of face-to-face interviews
      conducted during 2006. The sample consisted of 101 disabled persons who had
      suffered a stroke at least six months prior to the interview, and who had a
      functional status score of less than 95 as measured by the Barthel Index. Average
      monthly time spent on informal care was 94.6 hours, and the major source of
      opportunity cost was forgone unpaid work (43.5%). The average monthly monetary
      value of informal care was 4642.6 baht, based on 2006 prices. This study shows
      that providing informal care involves a substantial opportunity cost, implying a
      hidden value to Thai society.

PMID- 19573970
TI  - Convergence and divergence: differences in disability prevalence estimates in the
      United States and Canada based on four health survey instruments.
AB  - An analysis of data from the Joint Canada/United States Survey of Health (JCUSH),
      allows us to compare prevalence estimates that result from four different
      question sets designed to assess disability from a group of respondents residing
      in either Canada or the United States. Depending upon the question set used and
      the coding applied to the responses, age-standardized prevalence estimates varied
      widely in both countries. In the U.S. noninstitutionalized adult population,
      disability prevalence estimates ranged from as low as 15.3% to as high as 36.4%,
      while in Canada the estimates ranged from 13.4% to 37.3%. Concordance and
      discordance in identification as disabled among these question sets were also
      examined. In both countries, less than 20% of those identified as disabled by any
      question set were identified as disabled on all four question sets when using
      conservative response coding to define disability. Concordance in answers to
      these questions was also found to be associated with older age, single marital
      status, low education and low income in both countries. Discordance between
      question set pairs was similar across both countries whether among measures based
      on the same domains of disability or different domains of disability. The theory,
      methods and future of disability measurement in health surveys are discussed in
      light of these findings. We conclude that understanding and interpreting national
      prevalence estimates requires more thoughtful attention to the purposes for which
      data are being collected, the specific definition and operationalizations of
      disability for those purposes, the methodology used in the data collection and
      analysis process and the areas of both commonality and difference in the
      populations identified by each question set. In terms of cross-cultural
      comparisons, the use of a common set of questions and answer categories and
      similar survey methodologies provides much more robust results.

PMID- 19573971
TI  - A centralised, automated dental hospital water quality and biofilm management
      system using neutral Ecasol maintains dental unit waterline output at better than
      potable quality: a 2-year longitudinal study.
AB  - Most studies addressing biofilm formation in dental chair unit waterlines (DUWLs)
      have focused on a range of individual dental chair units (DCUs) and no studies on
      a centralised approach in a large number of DCUs have been reported to date.
      OBJECTIVES: To develop a centralised, automated water quality and biofilm
      management system serving the distribution network providing water to Dublin
      Dental Hospital's 103 DCUs, capable of maintaining DUWL supply and output water
      at better than potable quality standards in the long-term and requiring a minimum
      of human intervention. The potable water standard for the European Union does not
      specify an upper limit of aerobic heterotrophic bacteria, whereas a maximum of
      100 cfu/mL is permitted in bottled water. METHODS: Mains water of varying quality
      was treated by specifically selected automated filtration units to provide DCUs
      with water of consistent chemical composition. This water was then automatically
      disinfected using an electrochemically activated solution Ecasol (Trustwater
      Group, Clonmel, Ireland) (2.5 ppm) prior to distribution to DCUs. Microbiological
      quality of both DUWL supply and output water was monitored weekly by culture on
      R2A agar for 10 sentinel DCUs for a 100-week period. DUWLs were tested for the
      presence of biofilm by electron microscopy. RESULTS: Chemical composition of
      processed mains water consistently bettered potable water standards. DUWL supply
      water and output water aerobic heterotrophic bacterial counts averaged <1 and
      18.1 cfu/mL, respectively, from the 10 DCUs, compared to 88 cfu/mL for
      unprocessed mains water. This correlated with the absence of biofilm in DUWLs. No
      adverse effects due to Ecasol treatment of supply water were observed for DUWLs
      or DCU instruments. CONCLUSIONS: This centralised and automated water treatment
      and biofilm management system consistently maintains DUWL output water at better
      than potable quality simultaneously in a large number of DCUs over the long-term.

PMID- 19573972
TI  - Does Dual Operator CPR help minimize interruptions in chest compressions?
AB  - AIMS: Basic Life Support Guidelines 2005 emphasise the importance of reducing
      interruptions in chest compressions (no-flow duration) yet at the same time
      stopped recommending Dual Operator CPR. Dual Operator CPR (where one rescuer does
      ventilations and one chest compressions) could potentially minimize no-flow
      duration compared to Single Operator CPR. This study aims to determine if Dual
      Operator CPR reduces no-flow duration compared to Single Operator CPR.
      METHODOLOGY: This was a prospective randomised controlled crossover trial.
      Medical students were randomised into 'Dual Operator' or 'Single Operator' CPR
      groups. Both groups performed 4 min of CPR according to their group allocation on
      a resuscitation manikin before crossing over to perform the other technique one
      week later. RESULTS: Fifty participants were recruited. Dual Operator CPR
      achieved slightly lower no-flow durations than the Single Operator CPR (28.5%
      (S.D.=3.7) versus 31.6% (S.D.=3.6), P<or=0.001). Dual Operator CPR was associated
      with slightly more rescue breaths per minute (4.9 (S.D.=0.5) versus 4.5
      (S.D.=0.5), P=0.009. There was no difference in compression depth, compression
      rate, duty cycle, rescue breath flow rate or rescue breath volume. CONCLUSIONS:
      Dual Operator CPR with a compression to ventilation rate of 30:2 provides
      marginal improvement in no-flow duration but CPR quality is otherwise equivalent
      to Single Operator CPR. There seems little advantage to adding teaching on Dual
      Operator CPR to lay/trained first responder CPR programs.

PMID- 19573974
TI  - Simultaneous ventilation of two healthy subjects with a single ventilator.

PMID- 19573973
TI  - Hospital employees improve basic life support skills and confidence with a
      personal resuscitation manikin and a 24-min video instruction.
AB  - INTRODUCTION: The use of a personal resuscitation manikin with video instruction
      is reportedly as effective as traditional instructor-led courses in teaching lay
      people basic life support (BLS). We applied this method to an entire hospital
      staff to determine its effect on their practical and self-judged BLS skills.
      METHODS: All 5382 employees at Stavanger University Hospital were asked to learn
      or refresh their BLS skills with the personal resuscitation manikin and video
      instruction. Prior to and nine months after training, all employees were asked to
      rate their BLS skills on a scale from one to five. Additionally, randomly chosen
      study subjects were tested for BLS skills pre-training and six months post
      training during 2min of resuscitation on a manikin. RESULTS: In total, 5118
      employees took part in the BLS training program. The number of correct chest
      compressions increased significantly from 60 (5-102) to 119 (75-150) in the pre-
      vs. post-training periods, respectively, P<0.01, but the number of correct MTM
      ventilations did not change. Self-reported BLS skills increased from 3.1 (+/-1.0)
      pre-training to 3.8 (+/-0.8) post-training, P=0.031. CONCLUSION: After
      distributing a personal resuscitation manikin with video instruction to an entire
      hospital staff, the median number of correctly performed chest compressions
      doubled and self-confidence in BLS skills improved significantly. This is a
      simple and less time-consuming method than instructor-led courses in preparing
      hospital employees in the basic handling of cardiac arrest.

PMID- 19573975
TI  - Brain activity in near-death experiencers during a meditative state.
AB  - AIM: To measure brain activity in near-death experiencers during a meditative
      state. METHODS: In two separate experiments, brain activity was measured with
      functional magnetic resonance imaging (fMRI) and electroencephalography (EEG)
      during a Meditation condition and a Control condition. In the Meditation
      condition, participants were asked to mentally visualize and emotionally connect
      with the "being of light" allegedly encountered during their "near-death
      experience". In the Control condition, participants were instructed to mentally
      visualize the light emitted by a lamp. RESULTS: In the fMRI experiment,
      significant loci of activation were found during the Meditation condition
      (compared to the Control condition) in the right brainstem, right lateral
      orbitofrontal cortex, right medial prefrontal cortex, right superior parietal
      lobule, left superior occipital gyrus, left anterior temporal pole, left inferior
      temporal gyrus, left anterior insula, left parahippocampal gyrus and left
      substantia nigra. In the EEG experiment, electrode sites showed greater theta
      power in the Meditation condition relative to the Control condition at FP1, F7,
      F3, T5, P3, O1, FP2, F4, F8, P4, Fz, Cz and Pz. In addition, higher alpha power
      was detected at FP1, F7, T3 and FP2, whereas higher gamma power was found at FP2,
      F7, T4 and T5. CONCLUSIONS: The results indicate that the meditative state was
      associated with marked hemodynamic and neuroelectric changes in brain regions
      known to be involved either in positive emotions, visual mental imagery,
      attention or spiritual experiences.

PMID- 19573976
TI  - Resuscitation training for healthcare workers.

PMID- 19573977
TI  - Validation of the short form of the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Questionnaire (PISQ-12) in a Turkish population.
AB  - OBJECTIVE: To validate the Turkish translated version of short form of the Pelvic
      Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). STUDY DESIGN:
      After the test-retest reliability and internal consistency were established in a
      pilot study, 270 patients were enrolled and general and subscale scores of the
      questionnaire were calculated. All participants underwent the International
      Continence Society (ICS) prolapse score (POP-Q) and urodynamic assessment. Main
      scores and scores of Prolapse Quality of Life questionnaire (PQoL) and
      Incontinence Impact Questionnaire (IIQ-7) were compared between patients with
      incontinence+/-prolapse and asymptomatic women. RESULTS: 62.24% of the
      participants showed urodynamic abnormality and/or leakage with or without
      prolapse. 28.91% had prolapse stage 3 or higher diagnosed by the POP-Q system.
      PISQ-12 showed a high internal consistency (Cronbach's alpha was 0.89). For test
      retest reliability Spearman's rho was 0.72-0.79 for all domains. The mean scores
      of PISQ-12 were significantly better in asymptomatic women compared with the
      incontinence+/-prolapse group. Sexual function was negatively affected by
      prolapse and/or incontinence as assessed with PQoL and IIQ-7 questionnaires.
      CONCLUSION: The Turkish translated version of the PISQ-12 is a reliable,
      consistent and valid instrument to evaluate sexual functioning in women with
      urinary incontinence and/or pelvic organ prolapse. It is easy to understand that
      it may be easily administered and self-completed by the women.

PMID- 19573978
TI  - Thermodynamic analysis of protein unfolding in aqueous solutions as a multisite
      reaction of protein with water and solute molecules.
AB  - Thermal unfolding of ribonuclease A, lysozyme, and chymotrypsinogen A was
      analyzed as a multisite reaction of a protein molecule with water and solute
      molecules. The protein unfolding process in various solutions of sugars and
      denaturants was described well by the van't Hoff equation. The reciprocal form of
      the Wyman-Tanford equation, which describes the unfolded-to-folded protein ratio
      as a function of water activity, was successfully applied to obtain a good linear
      relationship. From this analysis, the role of water activity on protein stability
      was clearly explained and the contributions of hydration and solute binding to
      protein molecule were separately discussed in protein unfolding. General solution
      for the free energy of protein stability was obtained as a simple function of
      solute concentration.

PMID- 19573979
TI  - Environmental compliance: The good, the bad, and the super green.
AB  - Although many empirical studies have examined firms' decisions to participate in
      voluntary environmental programs, relatively few have examined why firms choose
      different levels of compliance with environmental regulations. This paper uses
      primary data to examine why some firms violate regulatory standards on water
      pollution, solid waste, toxic and hazardous waste, and hazardous air emissions,
      while others over-comply with them. The results suggest that different factors
      drive decisions to violate or over-comply with an environmental regulation. Some
      evidence was found to support the strategic behavior theory of environmental
      overcompliance, but no corroborating evidence was uncovered to support the green
      consumer theory.

PMID- 19573980
TI  - A proposal for reclassification of the Fuhrman grading system in patients with
      clear cell renal cell carcinoma.
AB  - BACKGROUND: The conventional Fuhrman grading system, which categorizes renal cell
      carcinoma (RCC) with grades I, II, III, and IV, is the most widely used predictor
      assessment of RCC cancer-specific mortality (CSM). OBJECTIVES: The aim of this
      study was to test the prognostic ability of simplified Fuhrman grading schemes
      (FGSs) that rely on two- or three-tiered classifications. DESIGN, SETTING, AND
      PARTICIPANTS: The current study addressed a population of 14064 patients with
      clear cell RCC who were treated with partial or radical nephrectomy between 1988
      2004, within nine Surveillance, Epidemiology, and End Results (SEER) cancer
      registries. MEASUREMENTS: Univariable and multivariable analyses as well as
      prognostic accuracy analyses were performed for various FGSs to test their
      ability to predict CSM rates. The conventional four-tiered FGS was compared to a
      modified two-tiered FGS in which grades I and II and grades III and IV were
      combined. A second simplified three-tiered FGS in which grades I and II were
      combined but grades III and IV were kept separate was also tested. RESULTS AND
      LIMITATIONS: The overall 5-yr CSM-free rate was 81.5%. All three FGSs achieved
      independent predictor status in multivariable analyses. Prognostic accuracy of
      multivariable models that relied on various FGSs was 83.6% for the modified two
      tiered FGS and 83.8% for both the conventional four-tiered and the modified three
      tiered FGS. CONCLUSIONS: Our findings indicate that the simplified FGSs perform
      equally as well as the conventional four-tiered FGS. The use of simplified
      grading schemes may represent an advantage for pathologists as well as for
      clinicians caring for patients with RCC.

PMID- 19573981
TI  - Micronutrient intake and risk of urothelial carcinoma in a prospective Danish
      cohort.
AB  - BACKGROUND: A range of plausible biological mechanisms support preventive effects
      of micronutrients in bladder cancer. So far, however, results from the few
      epidemiological studies on the relation have been inconsistent, with no clear
      associations found. OBJECTIVE: To evaluate the association between total,
      dietary, and supplemental intake of beta-carotene, folate, vitamins C and E, and
      risk of urothelial carcinoma (UC) and to explore whether the association differs
      with smoking status. DESIGN, SETTING, AND PARTICIPANTS: The association was
      evaluated in the Danish Diet, Cancer and Health Study, comprising 55,557 men and
      women aged 50-64 yr at inclusion with no previous cancer diagnosis. MEASUREMENTS:
      At baseline, all participants completed a detailed food frequency questionnaire
      including information on consumption of vitamin C, E, folate, and beta-carotene
      from diet and supplements. Incidence rate ratios (IRRs) of UC were calculated
      using Cox proportional hazards models. RESULTS AND LIMITATIONS: During a median
      of 10.6 yr of follow-up, 322 UC cases were diagnosed. Vitamin C, E, and folate
      showed no association with UC, regardless of source. There was a significantly
      lower risk of disease with dietary beta-carotene consumption (IRR: 0.82; 95%
      confidence interval [CI]: 0.69-0.98) and a borderline significant lower risk with
      total beta-carotene intake (IRR: 0.85; 95% CI: 0.73-1.00) pr. 5000 MUg of intake.
      We found a significant interaction between both dietary (p=0.005) and total
      (p=0.002) beta-carotene and smoking status, with a significant protective effect
      of beta-carotene seen among current smokers only. CONCLUSIONS: Our results
      indicate no preventive effect of vitamin C, E, or folate on UC. We found a
      protective effect of dietary, but not supplemental, beta-carotene on UC, but
      further studies are required.

PMID- 19573982
TI  - Antitumor activity and pharmacokinetic properties of ARS-interacting multi
      functional protein 1 (AIMP1/p43).
AB  - Although AIMP1 was identified as a component of the macromolecular aminoacyl tRNA
      synthetase complex involved in the cellular translation process, it was also
      found to be secreted as a cytokine having complex physiological functions. Among
      these, AIMP1's angiostatic and immune stimulating activities suggest its
      potential use as a novel antitumor therapeutic protein. Here we evaluated its
      antitumor efficacy in a mouse xenograft model bearing human stomach cancer cells.
      Intravenous injection of recombinant AIMP1 for 6 days resulted in significant
      decreases in both tumor volume and weight. Tumor volume decreased 31.1% and 54.0%
      when treated with AIMP1 at a concentration of 2mg/kg and 10mg/kg, respectively.
      Tumor weight decreased 29.1% and 52.2% when treated with AIMP1 at a concentration
      of 2mg/kg and 10mg/kg, respectively. Proliferating cell nuclear antigen (PCNA)
      staining of tumor tissues from AIMP1-treated mice (at both 2mg/kg and 10mg/kg)
      showed a 53% reduction of cells exhibiting an active cell cycle progression.
      Blood levels of tumor-suppressing cytokines such as TNF-alpha and IL-1beta
      increased in AIMP1-treated mice, whereas IL-12p40 and IFN-gamma levels remained
      unaltered. Thus, this work suggests that AIMP1 may exert its antitumor activity
      by inducing tumor-suppressing cytokines. In a pharmacokinetic study in rats after
      a single intravenous injection, AMP1 exhibited a low clearance showing a one
      compartmental disposition. However, due to a low volume of distribution, AIMP1
      had a short half-life of 0.1h. In a serum stability test, AIMP1 showed a half
      life of >60 min in human serum, 52 min in dog serum and 32 min in rat serum.

PMID- 19573983
TI  - Optimization of solid-phase extraction using developed modern sorbent for trace
      determination of ametryn in environmental matrices.
AB  - In recent years, there has been a significant increase in molecularly imprinted
      solid-phase extraction (MISPE) technique for the purification and clean-up of
      environmental samples. In this study, solid-phase extraction using the imprinted
      polymer has been optimized with the experimental design approach for a triazine
      herbicide, named ametryn with regard to the critical factors such as sample pH,
      sample concentration, sample flow-rate, sample volume, elution solvent, washing
      solvent and sorbent mass. These factors were evaluated statistically and also
      validated with spiked drinking water samples and showed a good reproducibility
      over six consecutive days as well as six within-day experiments. Also, in order
      to the evaluate efficiency of the optimized MISPE protocols, enrichment capacity,
      reusability and cross-reactivity of cartridges have been studied. Finally, a
      selective MISPE was successfully demonstrated for ametryn with a recovery of
      above 90% for spiked drinking water samples. It was concluded that the central
      composite design could prove beneficial for aiding the MIP and MISPE development.

PMID- 19573984
TI  - Microwave-enhanced H2O2-based process for treating aqueous malachite green
      solutions: intermediates and degradation mechanism.
AB  - This work was originally performed to compare H(2)O(2)-based degradation of
      aqueous malachite green (MG) under microwave (MW)-enhanced and conventional
      heating (CH)-enhanced conditions, with the whole reaction courses traced by UV
      vis spectrophotometer. The results showed that the higher discoloration rates of
      MG were available during MW-enhanced process, implying that the special heating
      way of MW might be more benefit for the generation of hydroxyl radicals than that
      of CH. Furthermore, major intermediates were separated and identified by HPLC-ESI
      MS and GC-MS techniques. On the basis of 53 intermediates, degradation mechanism
      was deduced as follows: firstly, N-de-methylation reactions. Secondly, adduction
      reactions. Thirdly, decomposition of conjugated structure reactions of MG.
      Fourthly, removal of benzene reactions. Finally, open-ring reactions.
      Additionally, results revealed that microwave-enhanced H(2)O(2)-based treatment
      had more advantages, such as higher degradation efficiency, and no removal of
      catalyst after treatment.

PMID- 19573986
TI  - A comparative study on the membrane based palm oil mill effluent (POME) treatment
      plant.
AB  - The discharge of palm oil mill effluent (POME) causes serious pollution problems
      and the membrane based POME treatment is suggested as a solution. Three different
      designs, namely Design A, B and C distinguished by their different types and
      orientations of membrane system are proposed. The results at optimum condition
      proved that the quality of the recovered water for all the designs met the
      effluent discharge standards imposed by the Department of Environment (DOE). The
      economic analysis at the optimum condition shows that the total treatment cost
      for Design A was the highest (RM 115.11/m(3)), followed by Design B (RM
      23.64/m(3)) and Design C (RM 7.03/m(3)). In this study, the membrane system
      operated at high operating pressure with low membrane unit cost is preferable.
      Design C is chosen as the optimal design for the membrane based POME treatment
      system based on the lowest total treatment cost.

PMID- 19573985
TI  - Kinetics of hexavalent chromium sorption on amino-functionalized macroporous
      glycidyl methacrylate copolymer.
AB  - Two samples of macroporous crosslinked poly(glycidyl methacrylate-co-ethylene
      glycol dimethacrylate), poly(GMA-co-EGDMA), with different porosity parameters
      were synthesized by suspension copolymerization and functionalized with ethylene
      diamine and diethylene triamine. The kinetics of Cr(VI) sorption by amino
      functionalized poly(GMA-co-EGDMA) was investigated under non-competitive
      conditions. Competitive kinetics was studied from following multicomponent
      solutions: Cu(II) and Cr(VI); Cu(II), Co(II), Cd(II) and Ni(II); Cr(VI), Cu(II),
      Co(II) and Cd(II) solutions. Two kinetic models (the pseudo-first and pseudo
      second-order) were used to determine the best-fit equation for the metals
      sorption by poly(GMA-co-EGDMA)-en and poly(GMA-co-EGDMA)-deta.

PMID- 19573987
TI  - Is there an association between psychological factors and the Complex Regional
      Pain Syndrome type 1 (CRPS1) in adults? A systematic review.
AB  - Complex Regional Pain Syndrome type 1 (CRPS1) is a complication after trauma or
      surgery. Its pathophysiology is still a matter of debate, and psychological
      factors have been suggested to play a role, although their influence is unclear.
      The aim of this study was to investigate the evidence for the influence of
      psychological factors on the onset and maintenance of CRPS1 in adults. In a
      systematic review, articles were selected using Cochrane, Pubmed/Medline,
      Psychinfo, and Cinahl since 1980. Only original articles and empirical studies
      were included. Based on these selection criteria, 31 articles were identified.
      Studies were evaluated and weighted using a quality assessment instrument. The
      few prospective studies do not report a relationship between CRPS1 and
      depression, anxiety, neuroticism, or anger. The results of the
      retrospective/cross-sectional studies yield contradictory results regarding
      psychological problems in patients with CRPS1. A majority show no association,
      and studies with a higher methodological quality lean to a conclusion of no
      relationship between psychological factors and CRPS1. The majority of included
      studies (N=24; 77%) had only a poor to moderate methodological quality. Although
      many patients with CRPS1 are stigmatized as being psychologically different, this
      literature review identified no relationship between CRPS1 and several
      psychological factors. Only life events seemed to be associated with CRPS1:
      patients who experienced more life events appeared to have a greater chance of
      developing CRPS1. More studies with greater methodological quality and more
      participants should be performed on the association between psychological factors
      and the development and course of CRPS1.

PMID- 19573988
TI  - Ketamine and chronic pain--going the distance.

PMID- 19573989
TI  - An assessment of the relative influence of pain coping, negative thoughts about
      pain, and pain acceptance on health-related quality of life among people with
      hemophilia.
AB  - Many people with hemophilia are affected by chronic arthritic joint pain as well
      as acute bleeding pain. In this cross-sectional study, 209 men with hemophilia A
      or B completed the Hemophilia Pain Coping Questionnaire (HPCQ), the Chronic Pain
      Acceptance Questionnaire (CPAQ), and the RAND 36-item Health Survey (SF-36), a
      measure of health-related quality of life. Multiple regression was used to test
      the influence of active pain coping, passive adherence coping, and negative
      thoughts about pain (HPCQ scales), and activity engagement and pain willingness
      (CPAQ scales), on physical and mental components of quality of life (SF-36 PCS
      and MCS scales), taking account of age, hemophilia severity, use of clotting
      factor, and pain intensity. Pain intensity had the main influence on physical
      quality of life and negative thoughts had the main influence on mental quality of
      life. Activity engagement and pain willingness had small but significant
      influences on physical and mental quality of life. Pain willingness also
      moderated and partly mediated the influence of pain intensity on physical quality
      of life, and activity engagement and pain willingness mediated the influence of
      negative thoughts on mental quality of life. Negative thoughts moderated and
      partly mediated the influence of pain intensity on mental quality of life. There
      was no evidence that active pain coping influenced quality of life. The findings
      suggest that quality of life in hemophilia could potentially be improved by
      interventions to increase pain acceptance and reduce negative thoughts about
      pain.

PMID- 19573990
TI  - Lattice distortions in GaN on sapphire using the CBED-HOLZ technique.
AB  - The convergent beam electron diffraction (CBED) methodology was developed to
      investigate the lattice distortions in wurtzite gallium nitride (GaN) from a
      single zone-axis pattern. The methodology enabled quantitative measurements of
      lattice distortions (alpha, beta, gamma and c) in transmission electron
      microscope (TEM) specimens of a GaN film grown on (0,0,0,1) sapphire by metal
      organic vapour-phase epitaxy. The CBED patterns were obtained at different
      distances from the GaN/sapphire interface. The results show that GaN is triclinic
      above the interface with an increased lattice parameter c. At 0.85 microm from
      the interface, alpha=90 degrees , beta=8905 degrees and gamma=11966 degrees . The
      GaN lattice relaxes steadily back to hexagonal further away from the sapphire
      substrate. The GaN distortions are mainly confined to the initial stages of
      growth involving the growth and the coalescence of 3D GaN islands.

PMID- 19573991
TI  - Probing non-dipole allowed excitations in highly correlated materials with
      nanoscale resolution.
AB  - Here, we demonstrate that non-dipole allowed d-d excitations in NiO can be
      measured by electron energy loss spectroscopy (EELS) in transmission electron
      microscopes (TEM). Strong excitations from (3)A(2g) ground states to (3)T(1g)
      excited states are measured at 1.7 and 3 eV when transferred momentum are beyond
      1.5 A(-1). We show that these d-d excitations can be collected with a
      nanometrical resolution in a dedicated scanning transmission electron microscope
      (STEM) by setting a good compromise between the convergence angle of the electron
      probe and the collected transferred momentum. This work opens new possibilities
      for the study of strongly correlated materials on a nanoscale.

PMID- 19573992
TI  - Selected parasitosis in cultured and wild fish.
AB  - While intensive aquaculture has and will continue to supply the ever growing
      population with highly nutritious protein, it also comes with problems which
      include more frequent outbreaks of diseases in fish farms and transmission of
      diseases between farmed and wild fish. We have selected four Phyla of
      economically important fish parasites for our present discussion-a
      haemoflagellate (Cryptobia salmositica), a microsporidian, (Loma salmonae), a
      monogenean (Gyrodactylus salaries) and two copepods (Lepeophtheirus salmonis,
      Caligus rogercresseyi). This review consists of two parts with a brief
      description of each parasite and its biology related to transmission, followed by
      discussions on epizootic outbreaks in both wild and farmed fish, interactions
      between wild and farmed fish, and disease prevention and control.

PMID- 19573993
TI  - Identification of host immune regulation candidate genes of Toxascaris leonina by
      expression sequenced tags (ESTs) analysis.
AB  - Toxascaris leonina adult worms live in the gastrointestinal tract of dog, cat,
      and fox, releasing eggs which enter the environment by the fecal route.
      Previously, we reported that T. leonina adult worm derived protein was able to
      inhibit OVA-specific Th2 responses, and in particular, immunization with parasite
      proteins exerts a more profound protective effect than allergen treatment. In
      order to gain greater insight into the relevant immune evasion mechanisms as well
      as basic scientific information, we have generated ESTs of T. leonina adult
      female worm and investigated their functions using euKaryotic Orthologous Groups
      (KOG) database analysis. From the randomly selected plasmids containing DNA
      inserts, a total of 487 reads were collected from the T. leonina adult worm cDNA
      library. The annotated ESTs were classified into 25 KOG categories; the most of
      ESTs (7.90%) were annotated with energy production and conversion, and the second
      highly annotated category is translation, ribosomal structure and biogenesis
      related ESTs (7.69%). We also identified many host-parasite immune related genes
      including C-type lectin, galectin, SXP, and cathepsin L-like cysteine protease
      coding genes. It is necessary to get more information regarding these genes for
      understanding about the mechanisms of immune evasion of Toxascaris.

PMID- 19573994
TI  - Toxicity of Piper aduncum L. (Piperales: Piperaceae) from the Amazon forest for
      the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
AB  - The mortality of 14-21-day-old Rhipicephalus (Boophilus) microplus larvae, and
      the mortality and fertility of groups of engorged adult females exposed to
      different concentrations of hexane, ethyl acetate and ethanol extracts of spiked
      pepper (Piper aduncum) were evaluated, using a completely randomized design with
      five treatment groups, two control groups, and two replicates for the larvae and
      five replicates for the adult females. Similar methodology was used to
      investigate the toxicity of the essential oil hydro-distillate (94.84%
      dillapiole) obtained from the P. aduncum crude hexane extract. The LC(50) of the
      hexane extract was 9.30 mg ml(-1) for larvae and the reproduction reduction
      ranged from 12.48% to 54.22%, while 0.1mg/ml(-1) of the essential oil induced
      100% mortality in larvae. Literature reports on natural products active against
      R. microplus were listed and compared with the results presented here. These
      results indicate that P. aduncum extracts, and particularly its essential oil,
      are potential alternative control agents for R. microplus.

PMID- 19573995
TI  - Intestinal alkaline phosphatase: the molecular link between rosacea and
      gastrointestinal disease?
AB  - Rosacea is a common inflammatory condition of the facial skin of unknown
      etiology, which frequently occurs in combination with gastrointestinal disorders.
      Many dietary and hormonal factors are known to affect the severity of rosacea
      symptoms, several of which also modulate the activity of the enzyme intestinal
      alkaline phosphatase (IAP). The role of IAP in inhibiting an inflammatory
      response to intestinal bacteria suggests a mechanism by which intestinal
      pathologies may be linked to the skin inflammation characteristic of rosacea.
      Analysis of alkaline phosphatase activity is routinely performed on blood
      samples, and methods to quantify enzyme activity of the intestinal isoform
      specifically have been described. Correlations between IAP activity and rosacea
      symptoms in patients and controls can thus be screened by noninvasive and
      inexpensive means. If IAP activity is found to be low in rosacea patients, acute
      symptoms could be treated with oral IAP supplementation, and trials of IAP
      activating medications currently used in gastrointestinal disease could be
      initiated in rosacea patients. More importantly, the safe and long-term control
      of rosacea could be undertaken by patients themselves through dietary
      modification to naturally increase IAP activity.

PMID- 19573996
TI  - Ultrasound assistant chemotherapy may be a novel modality for solid tumors.
AB  - Resistance to chemotherapy is the important reason for treatment failure in
      patients with cancer. Current methods which focus on the identification of more
      selective and potent drug resistance reversing agents are not satisfying. It is
      an urgent need for development of new approaches to overcoming drug resistance.
      The use of low power ultrasound in cancer therapy is a developing field.
      Recently, it was found that some anticancer drugs, upon ultrasonic irradiation,
      could create active oxygen species and effectively destruct cancer cells. This
      means that, in addition to cytotoxicity, these chemotherapeutic agents may be
      used as sonosensitizers and kill cancer cells by another mechanism. Moreover,
      local hyperthermia induced by ultrasound could enhance drug cytotoxicity. For the
      unique advantage of ultrasound, which are quite different from current therapy,
      we hypothesize that ultrasound assistant chemotherapy may be a new strategy to
      block drug resistance, which might enhance the efficacy of chemotherapeutic
      drugs, and reduce undesired side effects.

PMID- 19573997
TI  - Practical strategies for targeting NF-kappaB and NADPH oxidase may improve
      survival during lethal influenza epidemics.
AB  - The most foolproof way to promote survival in epidemics of potentially lethal
      influenza is to target, not highly mutable viral proteins, but rather
      intracellular signaling pathways which promote viral propagation or lung
      inflammation. NF-kappaB, activated in influenza-infected lung epithelial cells
      and macrophages, is one likely target in this regard, as it plays a role both in
      viral replication and in the excessive lung inflammation often evoked by
      influenza infection. Indeed, salicylates, which suppress NF-kappaB activation,
      have been shown to reduce the lethality of H5N1 avian-type influenza in mice.
      Another potential target is NADPH oxidase, as this may be a major source of
      influenza-evoked oxidant stress in lung epithelial cells as well as in phagocytes
      attracted to lung parenchyma. A number of studies demonstrate that oxidant stress
      contributes to overexuberant lung inflammation and lethality in influenza
      infected mice. The documented utility of N-acetylcysteine, a glutathione
      precursor, for promoting survival in influenza-infected mice, and diminishing the
      severity of influenza-like infections in elderly humans, presumably reflects a
      key role for oxidative stress in influenza. The lethality of influenza is also
      reduced in mice pretreated with adenovirus carrying the gene for heme oxygenase
      1; this benefit may be mediated, at least in part, by the ability of bilirubin to
      inhibit NADPH oxidase. It may be feasible to replicate this benefit clinically by
      administering biliverdin or its homolog phycocyanobilin, richly supplied by
      spirulina. If this latter speculation can be confirmed in rodent studies, a
      practical and inexpensive regimen consisting of high-dose salicylates, spirulina,
      and N-acetylcysteine, initiated at the earliest feasible time, may prove to have
      life-saving efficacy when the next killer influenza pandemic strikes.

PMID- 19573998
TI  - Is D2-40 a useful marker for distinguishing malignant mesothelioma from pulmonary
      adenocarcinoma and benign mesothelial proliferations?
AB  - Since pulmonary adenocarcinomas, malignant mesotheliomas (MM), and sometimes
      benign mesothelial proliferations show a great histomorphological resemblance to
      each other, an immunohistochemical panel is usually necessary for differential
      diagnosis. D2-40 is an available monoclonal antibody, which is already in use as
      a lymphatic endothelial marker. It has also been suggested to be useful in
      identifying the mesothelial differentiation. The aim of this study is to compare
      D2-40 immunostaining in MM, pulmonary adenocarcinoma, and benign mesothelial
      proliferations. In this retrospective study, D2-40 immunostaining was
      investigated in 37 cases of MM, 36 cases of pulmonary adenocarcinoma, and 31
      cases of benign mesothelial proliferation. The diagnosis of MM had previously
      been confirmed by a panel including calretinin, CK5/6, and CEA. Predominantly
      membranous immunoreactivity was observed in 51% of MMs and in 55% of benign
      mesothelial proliferations. All the 36 pulmonary adenocarcinomas were negative.
      These results were statistically significant (p<0.001). We believe that D2-40 may
      be helpful in the differential diagnosis of MM from pleural involvement of
      pulmonary adenocarcinoma.

PMID- 19573999
TI  - A "community-friendly" version of integrated group therapy for patients with
      bipolar disorder and substance dependence: a randomized controlled trial.
AB  - BACKGROUND: Integrated group therapy, a new treatment for patients with bipolar
      disorder and substance use disorder, has previously been found to be efficacious
      in reducing substance use, but its length (20 sessions) and need for highly
      trained therapists may limit its adoption in substance use disorder community
      treatment programs. This paper compares a briefer (12 session) version of
      integrated group therapy, led by substance use disorder counselors without
      previous cognitive-behavioral training or bipolar disorder experience, to group
      drug counseling. METHODS: Sixty-one patients with bipolar disorder and substance
      dependence, taking mood stabilizers, were randomized to 12 sessions of integrated
      group therapy (n=31) or group drug counseling (n=30). RESULTS: Analyses of
      primary outcomes showed trends favoring integrated group therapy, with greater
      reduction in substance use during follow-up and a greater decline in risk of mood
      episodes during treatment. Secondary analyses favored integrated group therapy,
      with a significantly greater likelihood of achieving total abstinence, a
      significantly shorter time to the first abstinent month, and a significantly
      greater likelihood of achieving a "good clinical outcome" (a composite measure
      encompassing both substance use and mood simultaneously). CONCLUSIONS: A
      shortened version of integrated group therapy can be delivered successfully by
      substance use disorder counselors, with better overall outcomes than those
      achieved with group drug counseling.

PMID- 19574000
TI  - The cost of treating addiction from the client's perspective: results from a
      multi-modality application of the Client DATCAP.
AB  - There is a considerable disparity between the number of individuals who need
      substance abuse treatment and the number who actually receive it. This is partly
      due to the fact that many individuals with substance use disorders do not
      perceive a need for formal treatment. Another contributing factor, however, is a
      discrepancy between the real and perceived cost of services. Although many cost
      evaluations of substance abuse treatment have been conducted from the treatment
      provider perspective, less is known about the client-specific costs of attending
      treatment (e.g., lost work and leisure time, transportation, out-of-pocket and in
      kind payments). Concerns about financial and other barriers to participating in
      treatment have encouraged addiction researchers to more carefully consider these
      previously unmeasured costs. To address this information gap, we administered the
      Client Drug Abuse Treatment Cost Analysis Program (Client DATCAP) to 302 clients
      (representing a total of 302 outpatient and 142 inpatient treatment episodes) as
      part of a larger study examining the cost-effectiveness of interventions designed
      to improve treatment linkage and engagement in Dayton, Ohio. The value of a
      client's time accounted for the largest component of total cost (more than 59%).
      The cost per visit for outpatient clients ranged from $19 for outpatient
      methadone to $38 for intensive outpatient/aftercare treatment. The average cost
      per day of treatment for inpatient clients was $235. Policy makers and treatment
      providers now have a broader view of the opportunity cost of addiction treatment
      and can use this information to support initiatives for improved treatment access
      and delivery.

PMID- 19574002
TI  - "Candidatus Bartonella thailandensis": a new genotype of Bartonella identified
      from rodents.
AB  - Bartonella species, intracellular parasite of erythrocytes and endothelial cells,
      are zoonotic pathogens of wild and domestic animals including rodents. Many
      species of rodents are commensally infected with a few Bartonella species in
      Asia. However, there are only few reports on detection of Bartonella in Thailand.
      Our objective was to detect the presence of Bartonella species in rodents from
      Thailand. Among 247 rodents captured in five provinces from Thailand we
      identified Bartonella species using molecular methods targeting three genes i.e.
      citrate synthase (gltA), beta-subunit of the RNA polymerase (rpoB) and cell
      division protein gene (ftsZ) and the 16S-23S rRNA intergenic spacer (ITS).
      Overall, we found 21 rodents being infected with a Bartonella species including
      seven B. coopersplainsensis, four B. phoceensis, six B. queenslandensis, one B.
      rochalimae, one Bartonella sp. RN24BJ and two genotypes of a new Bartonella that
      we propose to give the provisional status "Candidatus Bartonella thailandensis".
      To the best of our knowledge, these Bartonella species have been detected for the
      first time in Thailand.

PMID- 19574003
TI  - Circulating gonadotropins levels and contribution of different large antral
      follicles to isofolliculia in sheep.
AB  - The aim of this study was first to search for isofolliculia in right and left
      ovaries during postnatal development of Ouled Djellel ewe lambs, a non-seasonal
      breed of sheep. In addition, the contribution of different sizes of large antral
      follicles to this phenomenon was studied, and finally the variations in both
      plasma FSH and LH levels during this period of life were determined. Plasma was
      collected from groups of four ewe lambs at 0 (<24h), 1 week, and every 2 weeks
      from 4 to 14 weeks of age. Thereafter, each group was slaughtered, right and left
      ovaries recovered, weighed and their length and width measured. One ovary was
      fixed in Bouin-Holland's solution and prepared for histological study. The other
      one was immediately frozen and cut in a cryostat and prepared for histochemical
      study. This latter method was used to detect the activity of alkaline
      phosphatase, lactate dehydrogenase, NADH(2)-tetrasolium reductase, and glucose-6
      phosphate dehydrogenase enzymes. Number and size of antral follicles and their
      contribution to isofolliculia were determined from ovarian sections of both
      studies. Isofolliculia was seen in right and left ovaries of Ouled Djellel ewe
      lambs at 4, 6, 8, and 10 weeks of age. This phenomenon was characterized by the
      presence of large antral follicles almost equal in size and total enzymatic
      inactivity in the interstitium. Weight and dimensions of right and left ovaries
      increased rapidly from birth to 4 weeks of age, and then rose gradually to week 8
      and then rising again to week 10, followed by a decline at 12 and 14 weeks of
      age. All large antral follicles contributed to isofolliculia in right and left
      ovaries but, the percentage of antral follicles <2mm at 4, 6, 8, and 10 weeks of
      age were significantly greater than the percentage of follicles > or =2 and <3mm
      and the contribution of follicles > or =3mm was the lowest. FSH levels increased
      slowly from birth to 6 weeks of age then, increased rapidly to week 10, followed
      by a decline at weeks 12 and 14. LH was low at birth and the level increased
      slowly to 8 weeks of age, followed by a further rapid increase at 10 weeks of
      age. All parameters studied did not show any significant differences between the
      right and left ovary. It was concluded that isofolliculia occurred between 4 and
      10 weeks of age in left and right ovaries of Ouled Djellel ewe lambs. This
      phenomenon was characterized by the increase of both ovarian weights and
      dimensions, and of plasma FSH and LH levels. All large antral follicles > or =1mm
      in diameter contributed to isofolliculia but the contribution of antral follicles
      <2mm was greater than the contribution of antral follicles > or =2.

PMID- 19574001
TI  - Designing a treatment protocol with voriconazole to eliminate Aspergillus
      fumigatus from experimentally inoculated pigeons.
AB  - To investigate the efficacy of voriconazole for the treatment of aspergillosis,
      three groups of six racing pigeons (Columba livia domestica) were inoculated in
      the apical part of the right lung with 2x10(7) conidia of an avian derived
      Aspergillus fumigatus strain. The minimal inhibitory concentration of
      voriconazole for this strain was 0.25 microg/ml. In two groups, voriconazole
      treatment was started upon appearance of the first clinical signs and continued
      for fourteen days. The third group was sham treated. The voriconazole-treated
      pigeons received voriconazole orally at a dose of 10 mg/kg body weight (BW) q12h
      (group 1) or 20 mg/kg BW q24h (group 2). Sixteen days post-inoculation all
      surviving pigeons were euthanized. Weight loss, clinical scores, daily mortality,
      lesions at necropsy and isolation of A. fumigatus were compared between all
      groups. In both voriconazole-treated groups, a significant reduction in clinical
      signs and lesions was observed. Administering voriconazole at 10 mg/kg BW q12h
      eliminated A. fumigatus and administering voriconazole at 20 mg/kg BW q24h
      reduced A. fumigatus isolation rates. Mild histological liver abnormalities were
      found in group 1 (10 mg/kg BW q12h), while mild histological as well as
      macroscopic liver abnormalities were found in group 2 (20 mg/kg BW q24h). In
      conclusion, voriconazole at 10 mg/kg BW q12h in pigeons reduces clinical signs
      and eliminates A. fumigatus in racing pigeons experimentally infected with A.
      fumigatus.

PMID- 19574004
TI  - Characteristics of stimulation of gonadotropin secretion by kisspeptin-10 in
      female goats.
AB  - The aims of the present study were to clarify the effect of kisspeptin-10 (Kp10)
      on the secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH),
      growth hormone (GH) and prolactin (PRL) in goats, and compare the characteristics
      of any response with those of the response to gonadotropin-releasing hormone
      (GnRH). The experiments were performed using four female goats (4-5 years old) in
      the luteal phase of estrous cycle. A single intravenous (i.v.) injection of 1, 5
      and 10 microg/kg b.w. (0.77, 3.85 and 7.69 nmol/kg b.w.) of Kp10 stimulated the
      release of LH. Maximum values were observed 20-30 min after the injection. On the
      other hand, Kp10 did not alter plasma GH and PRL concentrations significantly.
      Three consecutive i.v. injections of Kp10 (5 microg/kg b.w.) or GnRH (5 microg/kg
      b.w.: 4.23 nmol/kg b.w.) at 2-h intervals increased both plasma LH and FSH levels
      after each injection (P<0.05); however, the responses to Kp10 were different from
      a similar level of GnRH. The rate of decrease in LH and FSH levels following the
      peak was attenuated in Kp10-treated compared to GnRH-treated animals. These
      results show that Kp10 can stimulate the release of LH and FSH but not GH and PRL
      in female goats and suggest that the LH- and FSH-releasing effect of the i.v.
      injection of Kp10 is less potent than that of GnRH.

PMID- 19574005
TI  - Arsenic trioxide-induced apoptosis of Hep-2 cell line through modulating
      intracellular glutathione (GSH) level.
AB  - BACKGROUND: Since 1970s, a Chinese study group at Harbin Medical University First
      Hospital discovered the anticancer effect of arsenic trioxide (As2O3), it has
      become evident that apoptotic effects of As2O3 are not restricted to APL cells
      but also can be observed in other malignant cells in vitro, including non-APL
      acute myeloid leukemia cells, myeloma cells, and chronic myeloid leukemia cells,
      as well as various solid-tumor cells, such as esophageal, prostate, and ovarian
      carcinomas and neuroblastoma cells. OBJECTIVE: To investigated if As2O3 could
      induce cell death and apoptosis of Hep-2 cells, a laryngeal squamous cell
      carcinoma (LSCC) cell line. METHODS: Trypan blue exclusion assay, LDH release
      assay and cytometric method were used for the measurements of cell death and
      apoptosis. We measured intracellular GSH, ROS and mitochondrial membrane
      potential to explore the mechanisms of cell death and apoptosis induced by As2O3
      in Hep-2 cells. RESULTS: Trypan-blue-positive cells and the release of LDH into
      medium induced by As2O3 increased in a dose- and time-dependent manner. The rates
      of apoptosis increased induced by As2O3 in a dose- and time-dependent manner. In
      order to elucidate the mechanisms of cell death and apoptosis induced by As2O3 in
      Hep-2 cells through GSH, we found that As2O3 induced the decrease of
      intracellular GSH, increase of ROS and loss of mitochondrial membrane potential.
      And pretreatment of BSO, an inhibitor of GSH biosynthesis, depleted partly
      intracellular GSH and increased trypan-blue-positive cells, the release of LDH,
      apoptosis, ROS and loss of mitochondrial membrane potential. However,
      pretreatment of GSH had resistance to the changes to some extent as described
      above. CONCLUSION: As2O3-induced apoptosis of Hep-2 cell line through modulating
      intracellular GSH level.

PMID- 19574006
TI  - Heat shock pretreatment attenuates sepsis-associated encephalopathy in LPS
      induced septic rats.
AB  - Sepsis is the most common cause of mortality in intensive care units. Although
      sepsis-associated encephalopathy (SAE) is reported to be a leading manifestation
      of sepsis, its pathogenesis remains unclear. In our previous studies, we showed
      that heat shock pretreatment can reduce mortality in polymicrobial septic rats
      and protect the cerebral cortical function during hypoxia or drug-induced
      convulsion. In the present study, we investigated to what extent heat shock
      pretreatment might affect the development of SAE in septic rats and the possible
      mechanism behind its effect was discussed. To do this, we used lipopolysaccharide
      (LPS) to induce septic response in a SAE animal model. Heat shock pretreatment
      was performed and rectal temperature maintained between 41 and 42 degrees C for
      15 min using an electric heating pad. Electroencephalography (EEG) activity, a
      sensitive electrophysiological recording of electrical activity in the brain, was
      used as an indicator of cerebral cortical dysfunction in SAE. In LPS rats not
      pretreated with heat shock, the EEG background activity decreased 10 min after
      intraperitoneal administration of LPS. However, in rats pretreated with heat
      shock, this decrease was significantly attenuated. Untreated septic rats were
      also found to have earlier, more frequent epileptic spikes. In summary, we found
      that heat shock could attenuate the electro-cortical dysfunction in rats with LPS
      induced septic response, suggesting that heat shock response might potentially be
      used to prevent SAE in sepsis.

PMID- 19574007
TI  - [Impact of routine pediatric varicella vaccination on the epidemiology of herpes
      zoster].
AB  - OBJECTIVE: This literature review addresses the following question: what elements
      point to an impact of routine chicken pox vaccination of children on the
      incidence of shingles? DESIGN: The search strategy involved an electronic search
      (Medline database via PubMed) and crossed references. Articles were selected by
      reading their abstracts. RESULTS: There were few published studies dealing with
      the question. A total of 13 publications reported seven longitudinal studies on
      the incidence of shingles and six mathematical models. The population studies
      were all American, and reported discordant results, four reporting an increase,
      and three, stability in the incidence of shingles. Four of the six mathematical
      models concerned the impact of routine chicken pox vaccination on shingles
      epidemiology. All showed a transitory short-term increase in the incidence of
      shingles (on condition that vaccine was effective and coverage high) and a long
      term incidence of shingles lower than the current rate. CONCLUSIONS: The
      currently available data is insufficient for any conclusion to be drawn as to the
      impact of routine pediatric chicken pox vaccination on the incidence of shingles.
      Monitoring the incidence of shingles in countries either recommending or not such
      vaccination should be maintained.

PMID- 19574008
TI  - Prevalence of acute adverse reactions to gadobutrol--a highly concentrated
      macrocyclic gadolinium chelate: review of 14,299 patients from observational
      trials.
AB  - OBJECTIVE: To determine the safety and tolerability of gadobutrol in a large
      number of non-selected patients from routine clinical radiology practices.
      MATERIALS AND METHODS: Six prospectively planned, observational surveillance
      studies were conducted at more than 300 institutions in Europe and Canada from
      2000 to 2007. Demographic and medical status data, details of the diagnostic
      procedure, contrast agent administration and adverse drug reaction (ADR) data
      were collected using a standardized questionnaire. RESULTS: A total of 14,299
      patients were enrolled. The mean age of the patients was 53.7 years; 1.3% of the
      patients were <18 years old and 40.8% were 60 years or older. The body regions
      most frequently examined were head/neck/brain (54.3%), followed by spine (7.2%),
      pelvis/joints/limbs (6.7%) and multiple body regions (6.4%). Gadobutrol-enhanced
      magnetic resonance angiography (MRA) was performed in 14.7% of patients. Overall,
      the mean volume of gadobutrol administered for contrast-enhanced magnetic
      resonance imaging was 12 mL (0.16 mmol gadolinium [Gd]/kg body weight [BW]; mean
      BW: 75.5 kg), whereas for contrast-enhanced MRA the mean volume was 15.7 mL (0.21
      mmol Gd/kg BW). Seventy-eight of the 14,299 patients (0.55%) reported at least
      one ADR. Two (0.01%) serious ADRs were reported. The most frequently reported ADR
      was nausea, which occurred in 36 patients (0.25%). CONCLUSION: Gadobutrol 1.0M is
      very well tolerated and has a good safety profile. The occurrence of ADRs
      observed following the intravenous injection of gadobutrol is comparable with the
      published data of other Gd-based contrast agents.

PMID- 19574009
TI  - Unwrapping magnetic resonance phase maps with Chebyshev polynomials.
AB  - A phase-unwrapping algorithm, based on the method of moments, is introduced in
      this work. The proposed algorithm expands the phase map in terms of a two
      dimensional Chebyshev series. The expansion coefficients are calculated by
      exploiting the orthogonality of Chebyshev polynomials of the first kind. The
      performance of the proposed phase-unwrapping algorithm is tested on a synthetic
      phase map and experimental phase maps of a uniform phantom, a human brain and a
      mouse torso, all acquired from 3-T magnetic resonance (MR) scanners. To impose
      additional burdens on the algorithm, we introduced magnetic field inhomogeneities
      to the phantom and human brain data by an external gradient coil. The proposed
      phase-unwrapping algorithm is found to perform well on the phantom data set in a
      low signal-to-noise ratio (SNR) environment and on the synthetic data set. The
      proposed algorithm is also found to perform well in in vivo data sets of the
      human brain and mouse torso. Results obtained from the in vivo MR data sets show
      that the proposed algorithm produced unwrapped phase maps that are nearly
      identical to those produced by a widely used phase-unwrapping algorithm, PRELUDE
      2D in the fMRI Software Library.

PMID- 19574010
TI  - Isolation and structural elucidation of dapoxetine as an adulterant in a health
      supplement used for sexual performance enhancement.
AB  - A health supplement used for sexual performance enhancement was sent to Health
      Sciences Authority of Singapore for testing. An unknown compound was detected and
      isolated and its structure was elucidated using NMR, high-resolution MS, ESI
      MS/MS, UV and IR. The compound, dapoxetine, is reported to be a selective
      serotonin reuptake inhibitor under investigation for the treatment of premature
      ejaculation.

PMID- 19574011
TI  - Development and validation of LC-MS/MS method for the determination of
      cyproheptadine in several pharmaceutical syrup formulations.
AB  - A rapid and sensitive liquid chromatographic-tandem mass spectrometric (LC-MS/MS)
      method was developed and validated for the qualitative and quantitative assay of
      cyproheptadine (CP) in pharmaceutical samples. Diphenylpyraline hydrochloride
      (DPP) was used as an internal standard (IS). Two multiple reaction-monitoring
      (MRM) transitions for each analyte were observed: 288.1/96.1 and 288.1/191.2 for
      CP and 282.1/167.2 and 282.1/116.3 for DPP. The retention time of the drug was
      7.29 min. The analytical method was successfully validated for linearity (1-100
      ng/ml), intra-day precision, inter-day precision, and accuracy. The limit of
      detection (LOD) and limit of quantification (LOQ) were 0.86 and 0.98 ng/ml,
      respectively. The proposed method was applied to analyse the cyproheptadine
      content from seven different syrup formulations.

PMID- 19574012
TI  - Profiling of levoamphetamine and related substances in dexamphetamine sulfate by
      capillary electrophoresis.
AB  - A capillary electrophoresis method for the simultaneous determination of the
      enantiomeric purity of dexamphetamine as well as the analysis of 1R,2S-(-)
      norephedrine and 1S,2S-(+)-norpseudoephedrine as potential impurities has been
      developed and validated. Heptakis-(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin
      was chosen as chiral selector upon a screening of neutral and charged
      cyclodextrin derivatives. Separation of the analytes was achieved in a fused
      silica capillary at 20 degrees C using an applied voltage of 25 kV. The optimized
      background electrolyte consisted of a 0.1 M sodium phosphate buffer, pH 2.5,
      containing 10 mg/ml of the cyclodextrin. The assay was linear in the range of
      0.06-5.0% of the impurities based on a concentration of 2.0 mg/ml dexamphetamine
      sulfate in the sample solution. Analysis of commercial dexamphetamine sulfate
      samples revealed the presence of 3-4% of levoamphetamine while norephedrine or
      norpseudoephedrine could not be detected, indicating that the compound was
      prepared by fractionated crystallization of racemic amphetamine. Comparison with
      polarimetric measurements indicated that dexamphetamine with an enantiomeric
      excess as low as 80% still passes the pharmacopeial test of specific rotation
      while an amount of 0.06% of levoamphetamine can be detected by capillary
      electrophoresis.

PMID- 19574013
TI  - Determination of total, free and saliva mycophenolic acid with a LC-MS/MS method:
      application to pharmacokinetic study in healthy volunteers and renal transplant
      patients.
AB  - Mycophenolic acid (MPA) is the active moiety of mycophenoate mofetil (MMF), an
      ester prodrug widely used as an immunosuppressant. Therapeutic drug monitoring
      (TDM) of MPA is becoming mandatory for transplant patients received MMF therapy
      in the routine clinical practice because of large individual variability, dose
      related toxicity and the risk of acute rejection. In this study, a rapid,
      sensitive and selective LC-MS/MS method was developed and validated for the
      quantitative analysis of total and free MPA in plasma and in saliva that uses one
      identical liquid chromatographic and mass spectrometric condition. Following
      protein precipitation for total and saliva MPA, and ultrafiltration for free MPA,
      chromatographic separation was performed on an Allure PFP Propyl analytical
      column (100 x 2.1 mm, 5 microm, RESTEK Co., Bellefonte, PA, USA) with 0.1% formic
      acid in acetonitrile and 0.1% formic acid in water (45:55, v/v) as the mobile
      phases. The compounds were quantified by positive electrospray ionization tandem
      mass spectrometry. Selectivity, linearity, accuracy, precision, recovery, matrix
      effect, and saliva stability were evaluated during method validation. The
      validated method was applied to a pharmacokinetic study of MPA after an oral
      administration of a single 1000 mg of MMF to eight healthy male volunteers and
      750 mg bid of MMF to nine renal transplant patients.

PMID- 19574014
TI  - Development and validation of a sensitive and selective UHPLC-MS/MS method for
      quantitation of an investigational anti-malarial compound, 2-tert-butylprimaquine
      (NP-96) in rat plasma, and its application in a preclinical pharmacokinetic
      study.
AB  - An ultra-high performance liquid chromatographic tandem mass spectroscopy (UHPLC
      MS/MS) method was developed and validated for the quantification of an
      investigational anti-malarial entity, 2-tert-butylprimaquine (NP-96), in rat
      plasma. Simple protein precipitation by acetonitrile was used for the sample
      preparation. Effective separation of NP-96, internal standard (IS) and matrix
      components were achieved on an UHPLC column (Hypersil Gold C18, 50mmx2.1mm,
      1.9microm) using a mobile phase composed of acetonitrile and 20mM ammonium
      acetate, which was pumped in a gradient mode at a flow rate of 450microl/min.
      Selective reaction monitoring (SRM) was utilized for quantitation of the
      molecules. To increase sensitivity of the method, two ions of m/z 299 and m/z 231
      were selected for NP-96, while IS was monitored for an ion of m/z 489. The method
      was validated according to FDA guideline on bioanalytical method validation and
      showed good compliance. The intra-day and inter-day precision expressed as R.S.D.
      was lower than 15% at all the tested quality control levels, including upper and
      lower limits of quantification. The calibration range was 2.5-500ng/ml. Total
      runtime for the method was 5min, which was suitable to produce high-throughput
      results for pharmacokinetic evaluation.

PMID- 19574015
TI  - Women's experiences of health visitor delivered listening visits as a treatment
      for postnatal depression: a qualitative study.
AB  - OBJECTIVE: To explore women's experiences of health visitor delivered listening
      visits as a treatment for postnatal depression. METHODS: In-depth interviews with
      22 women who had received listening visits as a treatment for postnatal
      depression. RESULTS: All the women reported the visits as beneficial, although
      many of them had required additional intervention to manage their symptoms. Women
      who had a previous history of depression and women whose depression was not
      attributed to events in the postnatal period perceived the listening visits to be
      less beneficial. Receiving visits from a research health visitor, rather than
      their practice health visitor, was felt to be advantageous. CONCLUSION: Women
      with postnatal depression may report listening visits as helpful but insufficient
      to manage their depression. The extent to which women report listening visits as
      beneficial appears to be linked to the causes of their depression, the way in
      which the visits are delivered and by whom. PRACTICE IMPLICATIONS: Practitioners
      managing women with postnatal depression should discuss possible causes and
      previous episodes of depression before suggesting listening visits as a
      treatment. They need to explain what the visits will entail, ensure that
      additional types of treatment remain available and encourage women to utilise
      other forms of support.

PMID- 19574016
TI  - The relationship between nurses' religiosity and willingness to let patients
      control the conversation about end-of-life care.
AB  - OBJECTIVE: The study attempts to examine the relationship between nurses'
      religious beliefs and how nurses communicate with patients. METHOD: An online
      census survey was administered to graduate students in the School of Nursing at a
      Midwestern university. The survey was designed to measure: relational control, as
      measured by the subscales of dominance and task orientation in Burgoon and Hale's
      scale of relational communication; clinician empathy, as measured by the
      Jefferson scale of clinician empathy; and intrinsic and extrinsic religiosity,
      whether religious views are held for deep personal reasons or social reasons, as
      measured by the Maltby and Lewis scale. Data were analyzed using multiple
      regressions and one-way ANOVAs. RESULTS: Intrinsic religiosity and empathy were
      both associated with the willingness to relinquish relational control in certain,
      specific contexts, such as end-of-life care. CONCLUSION: Nurses who scored higher
      on a scale of intrinsic religious beliefs were more willing to let patients take
      control of conversations about end-of-life care. PRACTICE IMPLICATIONS: A nurse's
      religious beliefs can enhance the clinical experience without the nurse trying to
      impose his or her beliefs on the patient, as the nurse works to make sure the
      patient's religious beliefs are upheld.

PMID- 19574017
TI  - A randomized trial of transcutaneous electric acupoint stimulation as adjunctive
      treatment for opioid detoxification.
AB  - This pilot study tested the effectiveness of transcutaneous electric acupoint
      stimulation (TEAS) as an adjunctive treatment for inpatients receiving opioid
      detoxification with buprenorphine-naloxone at a private psychiatric hospital.
      Participants (N = 48) were randomly assigned to active or sham TEAS and received
      three 30-minute treatments daily for 3 to 4 days. In active TEAS, current was set
      to maximal tolerable intensity (8-15 mA); in sham TEAS, it was set to 1 mA. By 2
      weeks postdischarge, participants in active TEAS were less likely to have used
      any drugs (35% vs. 77%, p < .05). They also reported greater improvements in pain
      interference (F = 4.52, p < .05) and physical health (F = 4.84, p < .01) over
      time. TEAS is an acceptable, inexpensive adjunctive treatment that is feasible to
      implement on an inpatient unit and may be a beneficial adjunct to pharmacological
      treatments for opioid detoxification.

PMID- 19574018
TI  - Factors predicting the sentinel node metastases in T1 breast cancer tumor: an
      analysis of 1416 cases.
AB  - AIM: To determine the factors associated with the metastatic involvement of
      sentinel lymph node (SLN) biopsy in patients with early breast cancer. STUDY
      DESIGN: This was a retrospective study of patients with T1 invasive breast cancer
      who underwent SLN biopsy at Claudius Regaud Institute between January 2001 and
      September 2008. RESULTS: 1416 patients were recruited into this study. SLN
      metastases were detected in 368 patients (26%). Younger age, tumor size and
      location, histological type, nuclear grade, and lymphovascular invasion appear to
      be significant risk factors of SNL involvement. In multivariate analysis, tumor
      size, tumor location, histological type and lymphovascular invasion are
      significant factors. When the tumor size is >20 mm, the OR is 6.6 compared to a
      T1a tumor (3.145-14.175, p<0.001, confidence interval 95%). When the tumor is
      found in the inner quadrant, the risk of SLN involvement is reduced compared to
      external locations with an OR of 0.53 (0.409-0.709, p<0.001, confidence interval
      95%). Non-ductal/lobular compared to infiltrative ductal cancer have a lower risk
      of SLN involvement with an OR of 0.423 (0.193-0.927, p<0.03, confidence interval
      95%). Lymphovascular invasion increase the risk of positive SLN with an OR of 2.8
      (1.9-4.1, p<0.001, confidence interval 95%). CONCLUSION: It appears reasonable to
      avoid axillary lymph node dissection in older patients with T1a tumors of good
      histopathological type and in the absence of lymphovascular invasion.

PMID- 19574020
TI  - [The annual congress of Adarpef].

PMID- 19574019
TI  - [Place of recombinant activated factor VII in the treatment of severe haemorrhage
      in paediatric patients].

PMID- 19574021
TI  - [Control or not glycemia in intensive care unit: is it the right question?].

PMID- 19574022
TI  - [Fulminant and subfulminant hepatitis: causes and treatment].
AB  - Fulminant hepatitis is an emergency because within a few hours, the physician
      must find the cause of the hepatitis (not identified in 15 to 20% of cases), rule
      out any contraindication to liver transplantation, verify that it is indicated,
      and prevent and/or treat the complications associated with liver failure. Viruses
      (especially hepatitis viruses A and B), drugs, and toxic agents are the most
      common causes of fulminant hepatitis, with the proportions varying between
      countries. Hepatitis viruses, the leading cause through 1995-1996, have fallen
      behind drugs and in particular paracetamol, which is now the leading cause of
      this disease in Europe and in the United States. There are also other rarer
      causes: other viruses (e.g., herpes virus HSV1 or 2, hepatitis virus E,
      parvovirus B19, and chickenpox-herpes zoster), Wilson Disease, acute Budd-Chiari
      and Reyes syndromes, autoimmune hepatitis, neoplastic infiltration of the liver,
      hypoxic hepatitis, heatstroke, acute pregnancy-related steatosis, and the HELLP
      syndrome. Prognosis is essentially determined by neurological status, but is also
      affected very rapidly by damage to other organs. Liver transplantation has
      revolutionized the prognosis of fulminant hepatitis, causing survival to increase
      from 10-20% (all causes combined) to 75-80% at 1 year and 70% at 5 years. These
      patients can be treated only in specialized centers with access to liver
      transplantation and to different modern means of liver resuscitation
      (hypothermia, artificial liver support, albumin dialysis, monitoring intracranial
      pressure and cerebral perfusion, etc.) -all from the onset of the disease.

PMID- 19574023
TI  - [Liver transplantation in patients with hepatitis B virus, hepatitis C virus, or
      human immunodeficiency virus].
AB  - The current 5-year survival rate after liver transplantation for hepatitis B
      virus HBV-related liver disease is excellent (85 %) because of excellent
      prophylaxis against HBV reinfection, obtained by the combination of antiviral
      therapy before transplantation and both anti-HBs immunoglobulin and antiviral
      therapy afterwards. End-stage liver disease due to hepatitis C virus (HCV) is a
      major indication for liver transplantation. Results are not as good (65%) because
      HCV reinfection after transplantation is almost impossible to prevent, and it
      impairs patient and graft survival. Combination therapy with pegylated interferon
      and ribavirin must be administered at an early stage of HCV recurrence on the
      graft. Liver transplantation is feasible for HIV-infected patients. Results are
      excellent for HIV/HBV coinfected patients (100%). In HIV/HCV coinfected patients,
      however, the recurrence of HCV infection is more severe than in patients with HCV
      alone and survival thus lower. Very early anti-HCV therapy must be discussed.

PMID- 19574024
TI  - Fire-related cognitions moderate the impact of risk factors on adjustment
      following wildfire disaster.
AB  - This study builds upon current understanding of risk and protective factors for
      post-disaster adjustment by examining relationships between disaster-related
      cognitions, three empirically supported risk factors for poorer adjustment (i.e.,
      greater disaster impact, female gender, and racial/ethnic minority status), and
      three common post-disaster outcomes (i.e., depression, anxiety, and somatic
      complaints). Participants were 200 students exposed to wildfire disaster.
      Simultaneous hierarchical regression analyses revealed that, during the acute
      stress period: (1) disaster-related cognitions in interaction with fire impact
      and minority status, as well as gender, were related to anxiety symptoms, (2)
      cognitions were related to depression symptoms, and (3) cognitions in interaction
      with minority status, as well as fire impact, were related to somatic symptoms.
      No examined variables predicted symptom change.

PMID- 19574025
TI  - Intraosseous 'haemangioma' of the zygoma: more appropriately termed a venous
      malformation.
AB  - Vascular anomalies often affect the soft tissues and primary intraosseous lesions
      are uncommon, with only 33 cases reported in the zygoma. Intraosseous vascular
      anomalies of the zygoma have traditionally been designated 'haemangiomas' with
      little attempt to clarify the specific type of the lesion. Recently, specific
      immunohistochemical markers such as erythrocyte type glucose transporter protein
      1 (GLUT-1) have been described to differentiate haemangiomas and vascular
      malformations. The authors report a case of intraosseous venous malformation of
      the zygoma and provide supporting evidence to justify the nomenclature. The
      literature on zygomatic 'haemangiomas' is critically reviewed and the basis for
      their proper designation as venous malformations highlighted.

PMID- 19574026
TI  - Extensive genetic polymorphism in the haplotype STR-TNF and HLA class I with the
      onset and evolution of psoriasis vulgaris.

PMID- 19574027
TI  - Effects of hydroquinone and its glucoside derivatives on melanogenesis and
      antioxidation: Biosafety as skin whitening agents.
AB  - BACKGROUND AND OBJECTIVE: The biosafety of hydroquinone and its derivatives as
      skin whitening agent remains controversial. Here, we investigated the effects of
      hydroquinone, arbutin, and deoxyarbutin (d-arb) on melanogenesis and
      antioxidation using cultured melan-a melanocytes in the presence or absence of
      ultraviolet A (UVA)-induced oxidative stress and determined whether d-arb enables
      to be an alterative to hydroquinone and arbutin for skin whitening use. METHODS:
      d-arb was synthesized in this study by removing all hydroxyl groups from the
      glucose side-chain of arbutin. Tyrosinase activity was measured by (14)C-tyrosine
      incorporation, the intracellular reactive oxygen species (ROS) level was
      monitored by H(2)DCFDA fluorescence labeling, and the cell viability was
      determined by MTT assay in murine melan-a melanocytes treated with hydroquinone,
      arbutin and deoxyarbutin in the presence or absence of UVA-induced oxidative
      stress. RESULTS: The cytotoxicity of hydroquinone and arbutin except for d-arb
      was increased while the cells exposed to a nontoxic dose (3J/cm(2)) of UVA
      irradiation. Suppressed ROS generation was noted by the treatment of d-arb to
      compare with arbutin and hydroquinone. All three compounds had a similar
      inhibition on tyrosinase activity in dose-dependent manners with two- to three
      fold decreases over the untreated control. There was no change in expression of
      tyrosinase protein in cells treated with arbutin or hydroquinone, but a decreased
      protein expression of tyrosinase was seen in deoxyarbutin-treated cells.
      CONCLUSIONS: Deoxyarbutin exerts potent tyrosinase inhibition, lessened
      cytotoxicity, and certain antioxidation potential, may serve as an effective and
      safe alternative to hydroquinone for use in skin whitening.

PMID- 19574028
TI  - Gender-linked differences in human skin.
AB  - BACKGROUND: The physiology of body organs can be affected by gender. Skin and
      skin appendages are influenced by sex hormones. OBJECTIVE: This review work has
      been undertaken to point out the most conspicuous physiological differences
      observed between men's and women's skin. METHODS: The literature has been
      searched and relevant results have been gathered. RESULTS: Men's and women's
      skins differ in hormone metabolism, hair growth, sweat rate, sebum production,
      surface pH, fat accumulation, serum leptins, etc. Examples of differences in the
      proneness to cutaneous diseases and skin cancer are quoted. CONCLUSION: The
      knowledge of gender-linked cutaneous differences might help in preparing male
      specific products for more appropriate dermatological treatments or cosmetic
      interventions.

PMID- 19574029
TI  - ECT practice and psychiatrists' attitudes towards ECT in the Chuvash Republic of
      the Russian Federation.
AB  - The practice of electroconvulsive therapy (ECT) and the attitudes of
      psychiatrists towards ECT in the Chuvash Republic are described. A significant
      proportion of Chuvash psychiatrists had a patchy knowledge about ECT and held
      negative attitudes towards the treatment. Enhancing the knowledge about ECT and
      changing negative attitudes will require persistent educational efforts.

PMID- 19574030
TI  - Frontal EEG predictors of treatment outcome in major depressive disorder.
AB  - OBJECTIVE: To investigate the role of frontal EEG as predictor of clinical
      response to SSRIs or venlafaxine in major depressive disorder (MDD). METHOD: 82
      subjects (age 35.9+/-13.0; 47.6% female) meeting DSM-IV criteria for MDD entered
      an 8-week prospective treatment with SSRIs or venlafaxine. At baseline and week 1
      we recorded serial, 4-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz). We evaluated
      prospectively the relative theta power as predictor of treatment outcome. We also
      developed an Antidepressant Treatment Response (ATR) index using EEG parameters
      assessed at baseline and week 1. RESULTS: 45 subjects (54.9%) responded to
      treatment (HAM-D-17 reduction>or=50%). At baseline, frontal relative theta power
      (i.e., 4-8 Hz power/2-20 Hz power) was significantly (p=0.017) lower (21%) in
      treatment responders than in non-responders (24%). Baseline relative theta power
      predicted treatment response with 63% accuracy [64% sensitivity, 62% specificity,
      66% area under the receiver operator curve (AUROC) (p=0.014)]. Relative theta
      power at week 1 predicted treatment response with 60% accuracy [62% sensitivity,
      57% specificity, 61% AUROC (p=0.089)]. ATR predicted response with 70% accuracy
      [82% sensitivity, 54% specificity, 72% AUROC (p=0.001)]. CONCLUSION: Using
      automated analysis of frontal EEG collected during the first week of
      antidepressant treatment it may be possible to facilitate prediction of SSRI or
      venlafaxine efficacy in MDD.

PMID- 19574032
TI  - Dramatic response to platinum in a patient with cancer with a germline BRCA2
      mutation.
AB  - We present a case of dramatic response of poor prognosis cancer in a lady with a
      germline mutation in the BRCA2 gene who was exposed to platinum containing
      chemotherapy. She is cancer-free 10 years' later. Such cases provide clinical
      scenarios for the basis of trials of platinum-like agents in individuals with
      BRCA mutations who develop cancer.

PMID- 19574031
TI  - Shock membrane electropotential drops and limited diffusive distance of beta
      amyloids in cerebral neurons are detrimental enhancement to Alzheimer's diseases.
AB  - Molecular physicobiochemical calculations indicated that the metallic ion binding
      to beta-amyloids (Abeta) may induce production of hydrogen peroxide, which
      triggers the Ca ion redistribution from the extracellular to the intracellular
      compartmentation, resulting in a transient membrane electropotential drop by at
      least 208.06 mV. Moreover, using the Mark and Houwink empirical equation, we
      predicted that the diffusible distances of all Abeta identities would be confined
      in a very tiny region within a radius less than 3.96 x 10(-4)cm in brain at 192h
      after produced. Because of the inherent tendency of aggregation behaved by the
      Abetas, the maximum diffusion coefficient and inherent viscosity were 8.24 x 10(
      15)cm(2)s(-1) and 72.15 cps for the 12 mers (40.8 kDa), the largest soluble form
      of ABs. Conclusively, we have quantitatively predicted that the shock membrane
      potential drop (Deltaphi>208.06 mV) and limited diffusible distance (<3.96 x 10(
      4)cm) in the brain would contribute the major detrimental effects to the neurons
      in the Alzheimer's diseases.

PMID- 19574033
TI  - A genetically engineered whole-cell pigment-based bacterial biosensing system for
      quantification of N-butyryl homoserine lactone quorum sensing signal.
AB  - N-acyl homoserine lactone (AHL) is a widely conserved quorum sensing (QS) signal
      of gram-negative bacteria and has received attention in fighting against human
      diseases and environmental pollution. However, a method for quantifying AHL is
      lacking although it is urgently required for diagnosis and bioprocess
      manipulation. This work screened out an aromatics degrader Pseudomonas aeruginosa
      for biosensing system development, which produced a blue-green pigment regulated
      by the RhlI-RhlR QS system. By taking advantage of the recognition of N-butyryl
      homoserine lactone (BHL, the signal molecule of RhlI-RhlR QS system and an AHL)
      by the product of rhlR, a new whole-cell biosensor P. aeruginosa Delta rhlIR/pYC
      rhlR (rhlI(-)rhlR(++)) was developed. It was constructed through abolishing its
      BHL production by in-frame deletion of rhlIR and over-expressing rhlR by
      introducing a multi-copy plasmid pYC-rhlR into Delta rhlIR. By using the pigment
      production which responded to exogenous BHL as biosensor output, BHL
      quantification in samples was simply done spectrophotometrically. Under optimum
      conditions, the calibration curve had the limit of detection (LOD), the 50%
      activation/effect concentration, the limit of quantification (LOQ), and the
      quantitative detection range of 1.3 nM, 2.77+/-0.45 microM, 5.7 nM and 0.11-49.7
      microM, respectively. The biosensor output was stable, culture samples could be
      stored 10 days under -20 degrees C, and this sensing system was resistant to
      interferences by toxic aromatic pollutants. It was successfully applied to
      environmental samples even without extraction. The new whole-cell biosensing
      system provided a simple, stable, toxic pollutants-tolerant, and cost-effective
      tool for quantitative investigation of the QS signals' role in environmental
      processes.

PMID- 19574034
TI  - Change in microbial communities in acetate- and glucose-fed microbial fuel cells
      in the presence of light.
AB  - Power densities produced by microbial fuel cells (MFCs) in natural systems are
      changed by exposure to light through the enrichment of photosynthetic
      microorganisms. When MFCs with brush anodes were exposed to light (4000 lx),
      power densities increased by 8-10% for glucose-fed reactors, and 34% for acetate
      fed reactors. Denaturing gradient gel electrophoresis (DGGE) profiles based on
      the 16S rRNA gene showed that exposure to high light levels changed the microbial
      communities on the anodes. Based on 16S rRNA gene clone libraries of light
      exposed systems the anode communities using glucose were also significantly
      different than those fed acetate. Dominant bacteria that are known exoelectrogens
      were identified in the anode biofilm, including a purple nonsulfur (PNS)
      photosynthetic bacterium, Rhodopseudomonas palustris, and a dissimilatory iron
      reducing bacterium, Geobacter sulfurreducens. Pure culture tests confirmed that
      PNS photosynthetic bacteria increased power production when exposed to high light
      intensities (4000 lx). These results demonstrate that power production and
      community composition are affected by light conditions as well as electron donors
      in single-chamber air-cathode MFCs.

PMID- 19574036
TI  - Optimized isolation procedure for obtaining strongly actinide binding
      exopolymeric substances (EPS) from two bacteria (Sagittula stellata and
      Pseudomonas fluorescens Biovar II).
AB  - Different chemical extractants (NaCl, EDTA, HCl and NaOH) and physical methods
      (ultrasonication and heating) were examined by their efficacies of extracting
      "attached" exopolymeric substances (EPS) secreted by marine bacterium Sagittula
      stellata (SS) and terrestrial bacterium Pseudomonas fluorescens Biovar II (PF).
      Extraction by 0.5 N HCl for 3 h was best for SS while extraction by 0.05 N NaCl
      for 3-5 h was regarded as optimal for PF. Improvements in EPS purification
      included a pre-diafiltration step to remove the broth material and reduce the
      solution volume, thus the usage of ethanol, and time. The EPS harvested at the
      optimal time and purified by the improved method were enriched in
      polysaccharides, with smaller amounts of proteins, thus having amphiphilic
      properties. Isoelectric focusing of (234)Th or (240)Pu labeled EPS showed both
      actinides were strongly bound to macromolecules with low pI, similar to reported
      marine or soil colloidal natural organic matter (NOM).

PMID- 19574037
TI  - Biological synthesis of gold nanocubes from Bacillus licheniformis.
AB  - Microorganisms play an important role in the eco-friendly synthesis of metal
      nanoparticles. This study illustrates the synthesis of gold nanocubes using the
      bacterium Bacillus licheniformis after 48 h of incubation at room temperature.
      The morphology of the samples was analyzed using scanning electron microscopy
      (SEM) and the particles formed were characterized to be nanocubes. The size of
      gold nanocubes in aqueous solution has been calculated using UV-Vis spectroscopy,
      XRD and SEM measurements. The nanoparticles are found to be polydisperse
      nanocubes in the size range 10-100 nm.

PMID- 19574035
TI  - Emerging patterns in planarian regeneration.
AB  - In the past decade, the planarian has become an increasingly tractable
      invertebrate model for the investigation of regeneration and stem cell biology.
      Application of a variety of techniques and development of genomic reagents in
      this system have enabled exploration of the molecular mechanisms by which
      pluripotent somatic stem cells called neoblasts replenish, repair, and regenerate
      planarian tissues and organs. Recent investigations have implicated
      evolutionarily conserved signaling pathways in the re-establishment of anterior
      posterior (A-P), dorsal-ventral (D-V), and medial-lateral (M-L) polarity after
      injury. These studies have significantly advanced our understanding of early
      events during planarian regeneration and have raised new questions about the
      mechanisms of stem cell-based tissue repair and renewal.

PMID- 19574038
TI  - A new member of the short-chain dehydrogenases/reductases superfamily:
      purification, characterization and substrate specificity of a recombinant
      carbonyl reductase from Pichia stipitis.
AB  - A novel short-chain dehydrogenases/reductases superfamily (SDRs) reductase (PsCR)
      from Pichia stipitis that produced ethyl (S)-4-chloro-3-hydroxybutanoate with
      greater than 99% enantiomeric excess, was purified to homogeneity using
      fractional ammonium sulfate precipitation followed by DEAE-Sepharose
      chromatography. The enzyme purified from recombinant Escherichia coli had a
      molecular mass of about 35 kDa on SDS-PAGE and only required NADPH as an electron
      donor. The K(m) value of PsCR for ethyl 4-chloro-3-oxobutanoate was 4.9 mg/mL and
      the corresponding V(max) was 337 micromol/mg protein/min. The catalytic
      efficiency value was the highest ever reported for reductases from yeasts.
      Moreover, PsCR exhibited a medium-range substrate spectrum toward various keto
      and aldehyde compounds, i.e., ethyl-3-oxobutanoate with a chlorine substitution
      at the 2 or 4-position, or alpha,beta-diketones. In addition, the activity of the
      enzyme was strongly inhibited by SDS and beta-mercaptoethanol, but not by
      ethylene diamine tetra acetic acid.

PMID- 19574039
TI  - Fatty acid composition in lipid fractions lengthwise the mycelium of Mortierella
      isabellina and lipid production by solid state fermentation.
AB  - This paper investigates the correlation between mycelial age and fatty acid
      biosynthesis. The correlation was investigated by analyzing the lipid composition
      lengthwise the mycelium of the oleaginous fungus Mortierella isabellina, a
      potential producer of gamma-linolenic acid (GLA). Young mycelia were rich in
      polar lipids (glycolipids plus sphingolipids and phospholipids), while neutral
      lipid content increased in aged mycelia. In young mycelia, each polar lipid
      fraction contained almost 40% (w/w) polyunsaturated fatty acids (PUFAs), but this
      content decreased to less than 30% (w/w) in aged mycelia. On the other hand, PUFA
      content in neutral lipids fluctuated slightly with age. These results indicate
      that PUFA biosynthesis is favored in young, fast growing mycelia, while it
      decreases significantly in aged mycelia. This trend was also observed when we
      grew M. isabellina on pear pomace, an agro-industrial waste. Pear pomace cultures
      yielded significant amounts of lipid, which reached 12% (w/w) in dry fermented
      mass. The produced lipid was rich in GLA and the maximum GLA content in dry
      fermented mass was 2.9 mg/g.

PMID- 19574040
TI  - Modeling, simulation, and experimental validation for continuous Cr(VI) removal
      from aqueous solutions using sawdust as an adsorbent.
AB  - Continuous adsorption experiments were performed in a fixed-bed adsorption column
      to evaluate the performance of low-cost adsorbent (sawdust) developed for the
      removal of Cr(VI) from aqueous solutions. The effects of influencing parameters
      such as flow rate, mass of adsorbent, initial Cr(VI) concentration were studied
      and the corresponding breakthrough curves were obtained. The fixed-bed adsorption
      process parameters such as breakthrough time, total percentage removal of Cr(VI),
      adsorption exhaustion rate and fraction of unused bed-length were obtained. A
      mathematical model for fixed-bed adsorption column was proposed by incorporating
      the effect of velocity variation along the bed-length in the existing model. Pore
      and solid diffusion models were used to describe the intra-particle mechanism for
      Cr(VI) adsorption. The proposed mathematical model was validated with the
      literature data and the experimental data obtained in the present study and the
      model was found to be good for explaining the behavior of breakthrough curves.

PMID- 19574041
TI  - Preparation and properties of banana fiber-reinforced composites based on high
      density polyethylene (HDPE)/Nylon-6 blends.
AB  - Banana fiber (BaF)-filled composites based on high density polyethylene
      (HDPE)/Nylon-6 blends were prepared via a two-step extrusion method. Maleic
      anhydride grafted styrene/ethylene-butylene/styrene triblock polymer (SEBS-g-MA)
      and maleic anhydride grafted polyethylene (PE-g-MA) were used to enhance impact
      performance and interfacial bonding between BaF and the resins. Mechanical,
      crystallization/melting, thermal stability, water absorption, and morphological
      properties of the composites were investigated. In the presence of SEBS-g-MA,
      better strengths and moduli were found for HDPE/Nylon-6 based composites compared
      with corresponding HDPE based composites. At a fixed weight ratio of PE-g-MA to
      BaF, an increase of BaF loading up to 48.2 wt.% led to a continuous improvement
      in moduli and flexural strength of final composites, while impact toughness was
      lowered gradually. Predicted tensile modulus by the Hones-Paul model for three
      dimensional random fiber orientation agreed well with experimental data at the
      BaF loading of 29.3 wt.%. However, the randomly-oriented fiber models
      underestimated experimental data at higher fiber levels. It was found that the
      presence of SEBS-g-MA had a positive influence on reinforcing effect of the Nylon
      6 component in the composites. Thermal analysis results showed that fractionated
      crystallization of the Nylon-6 component in the composites was induced by the
      addition of both SEBS-g-MA and PE-g-MA. Thermal stability of both composite
      systems differed slightly, except an additional decomposition peak related to the
      minor Nylon-6 for the composites from the HDPE/Nylon-6 blends. In the presence of
      SEBS-g-MA, the addition of Nylon-6 and increased BaF loading level led to an
      increase in the water absorption value of the composites.

PMID- 19574042
TI  - Application of laccase-natural mediator systems to sisal pulp: an effective
      approach to biobleaching or functionalizing pulp fibres?
AB  - The effects of laccase-natural mediator systems (LMS) on sisal pulp and their
      potential for either biobleaching or functionalizing (via radical-coupling) its
      fibres were investigated. The enzyme treatment (L stage) was followed by
      extraction with hydrogen peroxide in order to determine whether observable
      effects could be enhanced by removing LMS-modified lignin. Four different plant
      phenols [viz. the p-hydroxycinnamic compounds sinapic acid (SNC), ferulic acid
      (FRC), coniferyl aldehyde (CLD) and sinapyl aldehyde (SLD)] were used as laccase
      redox mediators and their effects on pulp and effluents compared with those of
      the synthetic compound 1-hydroxybenzotriazole (HBT). During the L stage performed
      with HBT, laccase underwent a loss of 99% and 78% of the initial activity, in the
      absence and presence of pulp, respectively. With natural mediators inactivation
      was markedly reduced, being the residual activity between 65% and 100% of the
      initial one, in the presence of pulp. The pulp was found to protect the enzyme
      against inactivation: the activity was only reduced by 45% in its presence. Under
      the operating conditions used the natural mediators proved less efficient than
      HBT in facilitating pulp bleaching; rather, they tended to bind to pulp fibres.
      This effect could be used to functionalize fibres in order to improve intrinsic
      properties of pulp or introducing novel ones (e.g. antimicrobial, antioxidant,
      optical properties, etc.). This paper shows for the first time the application of
      laccase-mediator systems to sisal pulp.

PMID- 19574043
TI  - The effect of the acidity of rapeseed oil on its transesterification.
AB  - The aim of this work is to study the transesterification of vegetable oil with a
      high acid number at unchanged reaction conditions. Rapeseed oil was used as the
      raw material and its acid number was changed by the addition of oleic acid (from
      0.89 to 12.25 mg KOH/g). Methanol was used for transesterification (molar ratio
      of oil to methanol 1:6) and potassium hydroxide was used as a catalyst. After the
      reaction time, the residue of the catalyst was neutralised by gaseous carbon
      dioxide and the methanol excess was removed. After the separation of two phases,
      each of them was analyzed (in the ester phase: yield, content of methyl ester and
      acid number; in the glycerol phase: yield, density, viscosity, content of
      glycerol, soaps, methyl ester, potassium carbonate and hydrogen carbonate). The
      obtained data was compared with theoretical material balances and the effect on
      the saponification of oil was discussed. The results show that the yield of
      methyl ester (biodiesel) is significantly affected by a higher acid number, as
      well as enhanced soap formation. On the other hand, the conversion of the oil and
      acid number of the ester phase remain at constant values in studied borders.

PMID- 19574044
TI  - Metal ion CHElate-aSSisted LIGAtion (CHESS LIGA) for SNP detection on
      microarrays.
AB  - We developed a metal ion chelate-assisted ligation for SNP detection by
      microarray. An oligonucleotide probe was separated into two 9-10-mers bearing
      iminodiacetic residues at the gap point. Duplex formation with the DNA target was
      possible only if nickel ions were added, but a nucleotide substitution opposite
      the gap point prevented duplex formation. Here we demonstrate the application of
      this approach for SNP detection (A1298C) within the 5,10
      methylenetetrahydrofolate reductase gene on a microarray.

PMID- 19574045
TI  - Novel inhibitors of the alphavbeta3 integrin--lead identification strategy.
AB  - A novel approach to inhibition of the alphavbeta3 integrin is described, which
      uses compounds designed to generate nM potency without using the arginine binding
      site.

PMID- 19574046
TI  - Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the
      pathogenic yeast Candida glabrata with anions.
AB  - A beta-carbonic anhydrase (CA, EC 4.2.1.1), the protein encoded by the NCE103
      gene of Candida glabrata which also present in Candida albicans and
      Saccharomycescerevisiae, was cloned, purified, characterized kinetically and
      investigated for its inhibition by a series simple, inorganic anions such as
      halogenides, pseudohalogenides, bicarbonate, carbonate, nitrate, nitrite,
      hydrogen sulfide, bisulfite, perchlorate, sulfate and some isosteric species. The
      enzyme showed significant CO(2) hydrase activity, with a k(cat) of 3.8 x 10(5)s(
      1) and k(cat)/K(M) of 4.8 x 10(7)M(-1)s(-1). The Ca glabrata CA (CgCA) was
      moderately inhibited by metal poisons (cyanide, azide, cyanate, thiocyanate,
      K(I)s of 0.60-1.12 mM) but strongly inhibited by bicarbonate, nitrate, nitrite
      and phenylarsonic acid (K(I)s of 86-98 microM). The other anions investigated
      showed inhibition constants in the low millimolar range, with the exception of
      bromide and iodide (K(I)s of 27-42 mM).

PMID- 19574047
TI  - Part 1: Structure-Activity Relationship (SAR) investigations of fused pyrazoles
      as potent, selective and orally available inhibitors of p38alpha mitogen
      activated protein kinase.
AB  - A novel class of fused pyrazole-derived inhibitors of p38alpha mitogen-activated
      protein kinase (MAPK) is disclosed. These inhibitors were evaluated for their
      ability to inhibit the p38alpha enzyme, the secretion of TNFalpha in a LPS
      challenged THP1 cell line and TNFalpha-induced production of IL-8 in 50% human
      whole blood. This series was optimized through a SAR investigation to provide
      inhibitors with IC(50) values in the low single-digit nanomolar range in whole
      blood. Further investigation of their pharmacokinetic profiles led to the
      identification of two potent and orally bioavailable p38 inhibitors 10 m and 10
      q. Inhibitor 10 m was found to be efficacious in vivo in the inhibition of
      TNFalpha production in LPS-stimulated Lewis rats with an ED(50) of 0.1mg/kg while
      10 q was found to have an ED(50) of 0.05-0.07 mg/kg.

PMID- 19574048
TI  - Synthesis of radiolabeled cytarabine conjugates.
AB  - N4-Modified, novel Ara-C conjugate capable of radiolabeling with gamma ray
      emitting ((99m)Tc) as well as positron emitting ((18)F) radionuclides, that is,
      N4-hydrazine derivative was synthesized. The radiolabeling of N4
      (hydrazinonicotinyl)-1-beta-arabinofuranosyl cytosine (HAra-C) with (99m)Tc was
      performed with over 95% labeling yield. To label HAra-C with (18)F, 4
      fluoro((18)F)-benzaldehyde was synthesized from 4-formyl-N,N,N-trimethylanilinium
      triflate in 30% radiochemical yield; it quantitatively formed hydrazone
      derivative with HAra-C within 45min. The radiolabeled conjugates were analyzed by
      radio-UV-RP-HPLC. The cold precursors were characterized by (1)H, (13)C NMR.
      Additionally, HAra-C was evaluated for cytotoxicity in lung adenocarcinoma (H441)
      cells and found to be comparable in cell killing efficiency to that of Ara-C.
      Uptake of (99m)Tc-HAra-C in cultures of H441 cells and sensitive pancreatic
      cancer cells (MIAPaCa-2) was inhibited by nucleoside transporter inhibitor
      nitrobenzylthioinosine. The results suggest that (99m)Tc-labeled HAra-C is a
      substrate for the membrane nucleoside transporters, and that it may be used in
      molecular imaging of nucleoside transporter expression for the verification of
      potential anticancer efficacy of nucleoside drugs, such as Ara-C and gemcitabine.

PMID- 19574049
TI  - Comment on "Reversible cerebral vasoconstriction syndrome".

PMID- 19574050
TI  - Peripheral neuropathy and visual evoked potential changes in workers exposed to n
      hexane.
AB  - The aim of this study was to evaluate patients who had peripheral neuropathy and
      changes to their visual evoked responses resulting from exposure to n-hexane.
      Eighteen patients with acute or subacute neuropathy, who were working in a shoe
      factory, were investigated clinically and electrophysiologically. These
      evaluations were then repeated 9 months to 12 months after cessation of exposure
      to n-hexane. Results of the nerve conduction studies predominantly showed a
      decrease in motor and sensory conduction velocities. Between 9 and 12 months
      after cessation of exposure to n-hexane, 83.3% of patients had a complete
      clinical recovery. The electrophysiological studies also revealed improvement to
      the majority of motor and sensory nerve conduction velocities. The results of the
      visual evoked potential (VEP) studies were considered normal at admission,
      however, the P100 latencies at the 9-month to 12-month retest had improved (p <
      0.05). As the abnormalities identified with clinical examination and nerve
      conduction studies, and the subclinical abnormalities revealed through VEP
      assessment, could be reversed after exposure to n-hexane had ceased, the clinical
      prognosis was usually good.

PMID- 19574051
TI  - The importance of vertebral artery proximity to the odontoid process during
      anterior odontoid approaches.
AB  - The proximity of the vertebral artery (VA) to the odontoid process makes it
      vulnerable to injury during surgery. Knowledge of the quantitative anatomy of the
      VA groove is therefore necessary. In this study we assessed the spatial
      relationship between the VA and the odontoid process on cadavers by direct
      measurement and in patients by CT angiography. Our goal was to measure the
      distances from the VA and vertebrobasilar junction to the odontoid tip. The VA
      and odontoid process of 10 craniocervical cadavers ("cadavers") and of 20
      patients were evaluated and average measurements obtained. The measured
      parameters were: (i) distance from the right VA to the odontoid tip (right VA
      odontoid tip); (ii) distance from the left VA to the odontoid tip (left VA
      odontoid tip), and (iii) distance from the vertebrobasilar junction to the
      odontoid tip (vertebrobasilar-odontoid tip). On the cadavers, the right VA
      odontoid tip distance was 11.55mm, the left VA-odontoid tip was 11.02mm, and the
      vertebrobasilar junction-odontoid tip distance was 24.55mm. In patients, using CT
      angiography, the right VA-odontoid tip distance was 11.47mm and the left VA
      odontoid tip distance was 11.50mm. The VA-odontoid tip distance is important in
      anterior odontoid approaches. Since the odontoid process may be in close contact
      with the VA, the relationship between them should be evaluated preoperatively in
      all candidates for odontoid surgery using three-dimensional CT angiography.

PMID- 19574052
TI  - Inter- and intra-tester reliability of clinical measurement to determine medio
      lateral patellar position using a pachymeter or visual assessment.
AB  - The aim was to investigate inter-tester and intra-tester reliability and parallel
      reliability between a visual assessment method and a method using a pachymeter
      for locating the mid-point of the patella in determining the medial/lateral
      patella orientation. Fifteen asymptomatic subjects were assessed and the mid
      point of the patella was determined by both methods on two separate occasions two
      weeks apart. Inter-tester reliability was obtained by ANOVA and by intraclass
      correlation coefficient (ICC); intra-tester reliability was obtained by a paired
      t-test and ICC; and parallel reliability was obtained by Pearson's Correlation
      and ICC, for the measurement on the first and second evaluations. There was
      acceptable inter-tester agreement (p=0.490) and reliability for the visual
      inspection (ICC=0.747) and for the pachymeter (ICC=0.716) at the second
      evaluation. The inter-tester reliability in the first evaluation was unacceptable
      (visual ICC=0.604; pachymeter ICC=0.612). Although there was statistical
      similarity between measurements for the first and second evaluations for all
      testers, intra-tester reliability was not acceptable for both methods: visual
      (examiner 1 ICC=0.175; examiner 2 ICC=0.189; examiner 3 ICC=0.155) and pachymeter
      (examiner 1 ICC=0.214; examiner 2 ICC=0.246; examiner 3 ICC=0.069). Parallel
      reliability gave a perfect correlation at the first evaluation (r=0.828; p<0.001)
      and at the second (r=0.756; p<0.001) and reliability was between acceptable and
      very good (ICC=[0.748-0.813]). Both visual and pachymeter methods provide
      reliable and similar medial/lateral patella orientation and are reliable between
      different examiners, but the results between the two assessments at 2 weeks'
      interval demonstrated an unacceptable reliability.

PMID- 19574053
TI  - Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase.
AB  - Glucopyranosylidene-spiro-1,4,2-oxathiazoles were prepared in high yields by NBS
      mediated spiro-cyclization of the corresponding glucosyl-hydroximothioates. In an
      effort to synthesize analogous glucopyranosylidene-spiro-1,2,4-oxadiazolines,
      with a nitrogen atom instead of the sulphur, attempted cyclizations resulted in
      aromatization of the heterocycle with opening of the pyranosyl ring. Enzymatic
      measurements showed that some of the glucose-based inhibitors were active in the
      micromolar range. The 2-naphthyl-substituted 1,4,2-oxathiazole displayed the best
      inhibition against RMGPb (K(i)=160 nM), among glucose-based inhibitors known to
      date.

PMID- 19574054
TI  - Synthesis, antimalarial activity and cytotoxicity of substituted 3,6-diphenyl
      [1,2,4,5]tetraoxanes.
AB  - Substituted tetraoxanes with different substitution pattern on the aromatic ring
      were synthesized in order to explore the influence of different substituents in
      the antimalarial activity. Antimalarial activity of these compounds improves by
      the introduction of ethyl, iso-propyl or n-propyl groups in the aromatic ring but
      substitution with n-butyl or t-butyl leads decrease in antimalarial activity.
      Some of these compounds exhibit promising antimalarial activity. None of the
      compounds shows any toxicity against vero cells and three compounds (2a-2c) were
      tested against panel of six cell lines and none of these compounds showed any
      toxicity. X-ray crystal structure of compound 2w showed that tetraoxane ring is
      in the chair conformation with both the phenyl rings in the equatorial position.
      In addition, FeCl(3) mediated O-O bond scission of tetraoxanes (2a-2c) was also
      examined.

PMID- 19574055
TI  - Synergism of virtual screening and medicinal chemistry: identification and
      optimization of allosteric antagonists of metabotropic glutamate receptor 1.
AB  - We report the identification of novel potent and selective metabotropic glutamate
      receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit
      optimization. For ligand-based virtual screening, molecules were represented by a
      topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing
      map (SOM). The most promising compounds were tested in mGluR1 functional and
      binding assays. We identified a potent chemotype exhibiting selective
      antagonistic activity at mGluR1 (functional IC(50)=0.74+/-0.29 microM). Hit
      optimization yielded lead structure 16 with an affinity of K(i)=0.024+/-0.001
      microM and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology
      based receptor modelling suggests a binding site compatible with previously
      reported mutation studies. Our study demonstrates the usefulness of ligand-based
      virtual screening for scaffold-hopping and rapid lead structure identification in
      early drug discovery projects.

PMID- 19574056
TI  - Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1
      inhibitor for the treatment of diabetes.
AB  - PPARgamma and 11beta-HSD1 are attractive therapeutic targets for type 2 diabetes.
      However, PPARgamma agonists induce adipogenesis, which causes the side effect of
      weight gain, whereas 11beta-HSD1 inhibitors prevent adipogenesis and may be
      beneficial for the treatment of obesity in diabetic patients. For the first time,
      we designed, synthesized a series of alpha-aryloxy-alpha-methylhydrocinnamic
      acids as dual functional agents which activate PPARgamma and inhibit 11beta-HSD1
      simultaneously. The compound 11e exhibited the most potent inhibitory activity
      compared to that of the lead compound 2, with PPARgamma (EC(50)=6.76 microM) and
      11beta-HSD1 (IC(50)=0.76 microM) in vitro. Molecular modeling study for compound
      11e was also presented. Compound 11e showed excellent efficacy for lowering
      glucose, triglycerides, body fat, in well established mice and rats models of
      diabetes and obesity and had a favorable ADME profile.

PMID- 19574057
TI  - Characterization of glutathione reductase and catalase in the fronds of two
      Pteris ferns upon arsenic exposure.
AB  - To better understand the mechanisms of plant tolerance to high concentration of
      arsenic, we characterized two antioxidant enzymes, glutathione reductase (GR) and
      catalase (CAT), in the fronds of Pteris vittata, an arsenic-hyperaccumulating
      fern, and Pteris ensiformis, an arsenic-sensitive fern. The induction, activation
      and apparent kinetics of GR and CAT in the plants upon arsenic exposure were
      investigated. Under arsenic exposure (sodium arsenate), CAT activity in P.
      vittata was increased by 1.5-fold, but GR activity was unchanged. Further, GR was
      not inhibited or activated by the arsenic in assays. No significant differences
      in K(m) and V(max) values of GR or CAT were observed between the two ferns.
      However, CAT activity in P. vittata was activated by 200 microM arsenate up to
      300% compared to the control. Similar but much smaller increases were observed
      for P. ensiformis and purified bovine liver catalase (133% and 120%,
      respectively). This research reports, for the first time, the activation of CAT
      by arsenic in P. vittata. The increased CAT activities may allow P. vittata to
      more efficiently mediate arsenic-induced stress by preparing the fern for the
      impeding production of reactive oxygen species resulting from arsenate reduction
      to arsenite in the fronds.

PMID- 19574058
TI  - Reproducibility of osseous landmarks used for computed tomography based three
      dimensional cephalometric analyses.
AB  - PURPOSE: The aim of this paper was to measure the reproducibility of osseous
      landmark identification from two recently described three-dimensional (3D)
      cephalometric analyses: 3D-ACRO and 3D-Swennen analyses. The study population
      consisted of 13 patients examined with spiral 3D computed tomography (CT). We
      used a previously validated low-dose CT protocol. For each analysis, 22
      cephalometric reference landmarks were identified on 3D CT surface renderings.
      Forty-four reference landmarks were identified per patient. Two series of
      identifications were performed by two independent observers. In total, 3432
      imaging measurements were completed. The intra-observer reconstructed mean log
      was 1.210+/-1.042mm for the 3D-ACRO analysis, and 1.311+/-1.042mm for 3D-Swennen
      analysis (comparison: p=0.17 NS). The inter-observer reconstructed mean log was
      1.799+/-1.037mm for the 3D-ACRO analysis, and 2.465+/-1.036mm for 3D-Swennen
      analysis (comparison: p=0.000000002). The difference between the intra- and inter
      observer reconstructed mean logs were 1.486+/-1.057mm for 3D-ACRO and 1.880+/
      1.056mm for 3D-Swennen analysis. In conclusions: 3D-ACRO analysis was
      significantly more reproducible than 3D-Swennen analysis (p=0.0027) due to the
      use of a majority of highly reproducible cephalometric landmarks. Finally, we
      propose a classification scheme and exclusion criteria for reference landmarks
      used in 3D cephalometrics, based on inter-observer reproducibility and anatomical
      reality.

PMID- 19574059
TI  - Genome-wide association studies in type 1 diabetes, inflammatory bowel disease
      and other immune-mediated disorders.
AB  - Genome-wide association studies have delivered on the promise of uncovering
      genetic determinants of complex disease. In this review, we provide a summary of
      recent advances in the identification of multiple variants associated with
      autoimmune-mediated disorders; specifically type 1 diabetes and inflammatory
      bowel disease. Sixteen loci, all replicated in independent samples, have now been
      uncovered for type 1 diabetes and in excess of 40 for inflammatory bowel disease.
      The next steps are to identify the true causal variants underlying evidence of
      disease association and to leverage this information to improve diagnosis,
      prevention and cure of these diseases.

PMID- 19574060
TI  - Factor V Leiden mutation and antiphospholipid syndrome: risk factors for
      atherosclerotic and arterial thromboembolic disease.

PMID- 19574061
TI  - Biomechanical evaluation of distal biceps reconstruction with cortical button and
      interference screw fixation.
AB  - HYPOTHESIS: Tension slide repair maintains the strength of the standard cortical
      button repair but reduces gap formation at the repair. Distal biceps tendon
      repair with a suspensory cortical button has yielded the strongest published
      repair, despite observed gap formation and tendon pistoning. The tension slide
      technique (TST) was described to reduce gap formation while maintaining the
      strength of cortical button repair. This study evaluates the biomechanics of the
      TST compared with previously described EndoButton (Smith & Nephew, Memphis, TN)
      repair and the TST with and without an interference screw. MATERIALS AND METHODS:
      The study used 20 matched specimens: 5 had a standard cortical button repair, and
      5 had biceps repair with the TST. An additional 10 specimens underwent a TST, 5
      with an interference screw and 5 without. All were cyclically loaded for 3600
      cycles. Gap formation and load to failure were measured. RESULTS: The mean (SD)
      load to failure for standard technique was at 389 (148) N vs 432 (66) N for the
      TST (P = .28). The mean (SD) gap formation was 2.79 (1.43) mm with the standard
      repair and 1.26 (0.61) mm with the TST (P = .03). The mean (SD) load to failure
      with TST repair was 436 (103) N without the interference screw and 439 (94) N (P
      = 0.48) with the screw. The mean gap formation was 1.63 (1.09) mm without the
      screw and 1.45 (0.67) mm with the screw (P = .38.) CONCLUSION: This TST maintains
      the strength of the standard cortical button repair, but significantly reduces
      gap formation and motion at the repair site. LEVEL OF EVIDENCE: Basic science
      study.

PMID- 19574062
TI  - The glenoid in shoulder arthroplasty.
AB  - Total shoulder arthroplasty is a common treatment for glenohumeral arthritis. One
      of the most common failure modes of total shoulder arthroplasty is glenoid
      loosening, causing postoperative pain, limitation of function, and potentially,
      the need for revision surgery. The literature has devoted considerable attention
      to the design of the glenoid component; efforts to better understand the
      biomechanics of the reconstructed glenohumeral joint and identify factors that
      contribute to glenoid component loosening are ongoing. This article reviews the
      current state of knowledge about the glenoid in total shoulder arthroplasty,
      summarizing the anatomic parameters of the intact glenoid, variations in
      component design and fixation, the mechanisms of glenoid loosening, the outcomes
      of revision surgery in the treatment of glenoid component failure, and
      alternative treatments for younger patients.

PMID- 19574063
TI  - Cost-effectiveness of open versus arthroscopic rotator cuff repair.
AB  - BACKGROUND: Economic evaluation of surgical procedures is necessary in view of
      more expensive newer techniques emerging in an increasingly cost-conscious health
      care environment. This study compares the cost-effectiveness of open rotator cuff
      repair with arthroscopic repair for moderately size tears. MATERIALS AND METHODS:
      This was a prospective study of 30 consecutive patients, of whom 15 had an
      arthroscopic repair and 15 had an open procedure. Clinical effectiveness was
      assessed using Oxford and Constant shoulder scores. Costs were estimated from
      departmental and hospital financial data. RESULTS: At last follow-up, no
      difference Oxford and Constant shoulder scores was noted between the 2 methods of
      repair. There was no significant difference between the groups in the cost of
      time in the operating theater, inpatient time, amount of postoperative analgesia,
      number of postoperative outpatient visits, physiotherapy costs, and time off
      work. The incremental cost of each arthroscopic rotator cuff repair was pound675
      ($1248.75) more than the open procedure. This was mainly in the area of direct
      health care costs, instrumentation in particular. DISCUSSION: Health care policy
      makers are increasingly demanding evidence of cost-effectiveness of a procedure.
      This study showed both methods of repair provide equivalent clinical results.
      CONCLUSION: Open cuff repair is more cost-effective than arthroscopic repair and
      is likely to have lower cost-utility ratio. In addition, the tariff for the
      arthroscopic procedure in some health care systems is same as open repair.

PMID- 19574064
TI  - Custom-made prosthesis replacement for reconstruction of elbow after tumor
      resection.
AB  - HYPOTHESIS: The options for reconstruction after excision of a tumor around the
      elbow are technically difficult and limited. MATERIALS AND METHODS: We
      retrospectively reviewed 25 patients who underwent custom-made endoprosthetic
      reconstruction after tumor resection near the elbow between 1998 and 2007.
      RESULTS: At final follow-up, 14 patients (56%) were alive, and 11 (44%) had died
      of their disease. Local recurrence was encountered in 4 patients (16%).
      Complications occurred in 6 patients (24%), including vascular injury,
      neurapraxia of the radial nerve, and aseptic loosening in 4. The average
      Musculoskeletal Tumor Society 93 score was 23.9 points, and the average Mayo
      Elbow Performance score was 82 points. Pain was relieved in all patients,
      although some limitations of lifting ability were reported. Ten patients had an
      arc of elbow motion of more than 100 degrees after reconstruction. CONCLUSIONS:
      In most patients, local tumor resection and prosthetic reconstruction of the
      elbow can be done with oncologic safety, and provides good function with low
      rates of complications.

PMID- 19574066
TI  - Morphometry of the human bicipital groove (sulcus intertubercularis).
AB  - BACKGROUND: The bicipital groove is located between the greater and lesser
      tubercles at the proximal extremity of the humerus and extends inferiorly.
      Citations that anatomic variations of the groove could give rise to sliding of
      the biceps brachii muscle tendon led us to initiate a morphometric study on this
      groove. MATERIALS AND METHODS: The study was done on 50 dry humeral bones from
      adults of both genders and from both sides. A digital caliper rule was used to
      measure the length, thickness and width of the bicipital groove and the humerus.
      The angles of the bicipital groove were measured with a goniometer. RESULTS: The
      average length of the groove was 8.1 cm and it corresponded to 25.2% of the
      length of the humerus. The width at the midpoint of the groove was 10.1 mm and
      corresponded to 49.7% to 54.5% of the width of the humerus. The depth was 4.0 mm
      and corresponded to 18.8% of the depth of the humerus. The mean angle formed by
      the groove lips was 106 degrees . CONCLUSION: This study confirmed the
      variability of the measurements presented by the groove in relation to all the
      aspects considered. LEVEL OF EVIDENCE: Basic Science.

PMID- 19574065
TI  - A clinical comparison of two different double plating methods for intraarticular
      distal humerus fractures.
AB  - BACKGROUND: This study compared clinical outcomes in patients with intraarticular
      distal humerus fractures treated using 2 different double plating methods.
      METHOD: Seventeen patients were treated by perpendicular plating (group I) and 18
      by parallel plating (group II) methods. Arc of flexion averaged 106 degrees +/-23
      degrees in group I and 112 degrees +/-19 degrees in group II. RESULTS: Eleven
      patients in group I recovered full arc of flexion and 13 patients in group II
      achieved full arc of flexion. All patients obtained bone union, except 2 patients
      in group I. Nonunion in these patients developed in the supracondylar area.
      Complications developed in 6 patients in group I and in 8 in group II. No
      significant differences were found between the clinical outcomes of the 2o
      plating methods. CONCLUSION: Although more patients failed to achieve bony union
      in the perpendicular plating group, both parallel and orthogonal plates
      positioning can provide adequate stability and anatomic reconstruction of the
      distal humerus fractures. LEVEL OF EVIDENCE: 2.

PMID- 19574067
TI  - Computer simulation of humeral shaft fracture in throwing.
AB  - HYPOTHESIS: Throwing fractures of the humerus are well known, but the exact
      mechanism of injury is not clear. It has been postulated that these may be stress
      fractures because the forces have not seemed sufficient to cause acute fractures
      while throwing. MATERIALS AND METHODS: Using finite element analysis, we
      reproduced fractures of the humerus using 3-dimensional models built from
      computed tomography images of 5 healthy volunteers. To apply the load during
      throwing, we assumed that the humeral head was completely fixed, and external
      rotation torque was applied to the distal end of the humerus until the stress of
      the bone elements became greater than yield stress. We reproduced the fracture
      line by removing the bone elements. RESULTS: The maximum stress concentration was
      seen in the distal shaft, where a typical spiral fracture was created in all
      cases. In the humeral models, the torque required to initiate fracture ranged
      from 51 to 70 Nm. A strong correlation existed between the torque required to
      initiate fracture and thickness of the humeral cortical bone (R(2) = 0.74).
      CONCLUSION: These results indicate that thickness of the humerus represents one
      factor contributing to fractures that occur while throwing. LEVEL OF EVIDENCE:
      Basic science study.

PMID- 19574068
TI  - Tumors masked as frozen shoulders: a retrospective analysis.
AB  - BACKGROUND: It was reported that some shoulder tumors were misdiagnosed with
      frozen shoulder syndrome. The purposes of this study were to elucidate the
      incidence of the initial misdiagnosis with frozen shoulder syndrome among the
      patients with malignant shoulder tumors, and to clarify whether such initial
      misdiagnosis affected the time to make a final correct diagnosis or not. METHODS:
      Clinical records of 34 patients (age>40) with malignant shoulder tumors and those
      of 505 patients (age>40) with shoulder pain and stiffness were reviewed in the
      author's institute. The duration of the prediagnostic period was compared between
      the patients with and without an initial misdiagnosis as frozen shoulder
      syndrome. RESULTS: Among 34 tumor patients, 9 (26%) had been initially
      misdiagnosed with frozen shoulder syndrome. Two patients actually manifested
      shoulder pain and stiffness, although they did not have a record of misdiagnosis.
      Among 505 patients with shoulder pain and stiffness, 4 (0.8%) were diagnosed
      later as having malignant tumors. One of these 4 patients had been initially
      misdiagnosed with frozen shoulder syndrome. Consequently, 15 malignant tumors (10
      bone tumors and 5 soft tissue sarcomas) were identified. Seven of them were
      intraosseous humeral tumors and 4 were localized in the scapular region, where
      patients themselves could not find them. In 10 patients, initial misdiagnosis as
      frozen shoulder syndrome did cause a significant delay to reach the correct
      diagnosis as malignant tumors (P=.035). CONCLUSION: Physicians should carefully
      re-examine the frozen shoulder patients with repeated plain radiographs followed
      by further imaging studies, if the conservative therapy fails.

PMID- 19574069
TI  - Pelvic venous incompetence: reflux patterns and treatment results.
AB  - OBJECTIVE: To assess reflux patterns and the results of endovascular obliteration
      of ovarian veins in patients with symptomatic pelvic venous incompetence (PVI).
      METHODS: A total of 71 female patients (mean age 49 years) with signs of PVI on
      selective phlebography of the pelvic veins were included in the study. In 53
      cases (75%), recurrent varicose veins following previous surgery and stripping of
      the great saphenous vein were present and 51 patients (72%) were multiparous (>
      or = 2 children). Symptoms were scored on a visual analogue scale (VAS) assessing
      pelvic and lower limb pain. After duplex ultrasonography of the lower limb veins,
      in cases of suspected PVI, the presence of any reflux in the ovarian and pelvic
      veins was demonstrated by phlebography. In selected cases, endovascular treatment
      with embolisation was used. Follow-up assessment of symptoms was carried out at
      1, 2 and 3 years. RESULTS: The left ovarian vein (OV) and the right internal
      iliac vein (IIV) were most frequently affected by reflux (n=41, 58% each). In
      about half the number of patients, reflux was demonstrated in more than one of
      the main pelvic veins (n=38, 54%). An extension of reflux into varicose veins of
      the groin or lower limb was demonstrated in 44 patients (62%); 35 patients (49%)
      received treatment for their PVI by coil embolisation. Fifty-five patients (77%)
      completed follow-up. Patients with isolated ovarian vein incompetence, who were
      treated by embolisation, experienced a significant improvement of symptoms (mean
      symptom score 5.2 standard deviation (SD) 3.5 before and 1.2 SD 0.9 after
      embolisation treatment; p<0.0001), while patients with untreated incompetence did
      not show improvement in symptoms (mean score 4.5 SD 1.6 before and 5.1 SD 1.5
      after conservative treatment; non-significant (N.S.)). Improved symptoms were
      detected in patients with isolated IIV incompetence, who underwent embolisation
      treatment (mean symptom score 5.1 SD 2.5 before and 2.1 SD 1.6 after treatment;
      N.S.) although this did not reach statistical significance. Conservative
      treatment of patients with isolated IIV incompetence resulted in no relevant
      changes (mean score 4.2 SD 2.0 before and 4.5 SD 2.1 after treatment; N.S.).
      Worsening of symptoms was found in patients with combined reflux who underwent
      conservative treatment (mean score 5.3 SD 2.0 before and 6.5 SD 2.5 after
      treatment, N.S.). In case of combined OV and IIV reflux, isolated interventional
      treatment of incompetent ovarian veins did not improve symptoms at each interval
      of the follow-up (mean score 5.2 SD 2.1 before and 5.1 SD 2.6 after treatment,
      N.S.), while coiling of all reflux pathways resulted in symptom reduction; but
      this did not reach statistical significance due to the small numbers of patients
      (mean score 5.6 SD 2.2 before and 3.2 SD 2.1 after treatment, N.S.). CONCLUSIONS:
      Combined reflux in more than one pelvic vein is common. In these cases, isolated
      treatment of ovarian veins or conservative treatment is associated with a poor
      midterm clinical outcome. A clinical improvement was achieved only in patients
      with isolated ovarian vein incompetence.

PMID- 19574070
TI  - Comparison of locking and nonlocking plates in the treatment of mandibular
      condyle fractures.

PMID- 19574071
TI  - Toxicology and wildlife conservation in Europe: the inadequacy of current EU
      regulations.

PMID- 19574072
TI  - Laminitis--what's in a name?

PMID- 19574073
TI  - Nearly 10(6)-fold enhancements in intermolecular (1)H double-quantum NMR
      experiments by nuclear hyperpolarization.
AB  - Intermolecular Multiple-Quantum Coherences (iMQCs) can yield interesting NMR
      information of high potential usefulness in spectroscopy and imaging - provided
      their associated sensitivity limitations can be overcome. A recent study
      demonstrated that ex situ dynamic nuclear polarization (DNP) could assist in
      overcoming sensitivity problems for iMQC-based experiments on (13)C nuclei. In
      the present work we show that a similar approach is possible when targeting the
      protons of a hyperpolarized solvent. It was found that although the DNP procedure
      enhances single-quantum (1)H signals by about 600, which is significantly less
      than in optimized low-gamma liquid-state counterparts, the non-linear dependence
      of iMQC-derived signals on polarization can yield very large enhancements
      approaching 10(6). Cleary no practical amount of data averaging can match this
      kind of sensitivity gains. The fact that DNP endows iMQC-based (1)H NMR spectra
      with a sensitivity that amply exceeds that of their thermally polarized single
      quantum counterpart, is confirmed in a number of simple single-scan 2D imaging
      experiments.

PMID- 19574074
TI  - Laboratory issues in the implementation of the marker method.
AB  - Two important biomarkers for the identification of growth hormone or IGF-I
      administration are IGF-I and P-III-P. These substances are determined in plasma
      or preferably in serum. There are a number of assays on the market for IGF-I but
      only two for P-III-P. The principles behind these assays and the choice of assays
      for doping control purposes are discussed. The future possibility of
      quantification by mass spectrometry is also briefly discussed.

PMID- 19574076
TI  - Severe Weil's syndrome complicated by hemolytic anemia.

PMID- 19574075
TI  - Intra-lesional amphotericin B--worth a try, maybe for lots of things, but we need
      more data!

PMID- 19574077
TI  - [Necrotizing fasciitis and cellulitis of the upper limb resulting from centipede
      bite: two case reports].
AB  - Centipede bites occurring in tropical countries are rare, however vigilance must
      be exercised during activities in the open air and dwellings should be checked in
      the event of rain. The bite is very painful and can be accompanied by generalised
      signs. An initial wound disinfection and a check of antitetanus vaccination
      status is all that is usually needed to ensure an uneventful outcome. There are
      however, rare cases where local toxicity and a bacterial super-infection, often
      with Gram+ cocci, can lead to a cellulitis or even necrotizing fasciitis of the
      hand. The diagnosis of a centipede bite can be made by the double marks made by
      the fangs. Wound debridement and antibiotics led to a good outcome in both our
      cases.

PMID- 19574078
TI  - [Cervical cancer screening: a new tool to do one's best or doing one's best with
      a new tool?].

PMID- 19574079
TI  - [Update on malignant nonepithelial ovarian tumours].
AB  - Malignant nonepithelial ovarian tumours represent less than 20% of ovarian
      cancers in adults. Apart from haematological tumours, there are mainly germ cell
      tumours and sex cordstromal ovarian tumours. These tumours affect young women and
      are diagnosed in early stages associated with a good prognosis. The management of
      malignant nonepithelial ovarian tumours is difficult because they are rare and
      because we have to propose an appropriate oncological treatment, preserving
      fertility for these women of child-bearing age. We propose an update on recent
      data in the literature, focusing on management.

PMID- 19574081
TI  - Ultrasonic system for continuous washing of textiles in liquid layers.
AB  - The use of ultrasonic energy for washing of textiles has been tried several times
      without achieving practical development. In fact, the softness of the fibres
      makes the cavitation to produce small erosion effect and the reticulate structure
      of the fabric favours the formation of air bubble layers which obstruct wave
      penetration. In addition, a high proportion of water with respect to the wash
      load and a certain water degassing is required to assure efficiency and
      homogeneity in the wash performance. Such requirements have hindered the
      commercial development of the ultrasonic washing machines for domestic purposes.
      For specific industrial applications, a great part of these limitations may be
      overcome. This article deals with a new process in which the fabric is exposed to
      the ultrasonic field in a flat format. Such process has been implemented at
      laboratory and at semi-industrial stage by using specially designed power
      ultrasonic transducers with rectangular plate radiators. The cleaning effect is
      produced by the intense cavitation field generated by the plate radiator within a
      thin layer of liquid where the fabric is introduced. The homogeneity of such
      effect is achieved by the successive exposure of all the fabric areas to the
      intense acoustic field. In this paper the structure and performance of the
      developed system are shown.

PMID- 19574080
TI  - [Molecular biology usefulness for rapid diagnosis of Down's syndrome and common
      aneuploidies].
AB  - OBJECTIVE: Trisomy of chromosome 13, 18, 21 and sex chromosome aneuploidies are
      the most common chromosomal abnormalities encountered in prenatal screening and
      are responsible for polymaformative syndrome associated with severe mental
      retardation. This high degree of morbidity justifies the prenatal diagnosis of
      these aneuploidies. Fetal nuchal translucency measurement and maternal serum
      biochemical marker assessment are the method of choice used for antenatal
      screening of aneuploidies. This prenatal screening leads to numerous maternal
      samplings followed by karyotyping which is cost-effective, time consuming, while
      results are generally returned between 2 and 3 weeks. Our study describes the
      research of common aneuploidies by molecular biology. We have used on one hand
      the MLPA kit (MRC Holland) based on amplification of specific DNA probes that
      hybridize with chromosomes 13, 18, 21, X, Y. On the other hand we have developed
      multiplex fluorescent PCR, amplifying microsatellite DNA sequences. PATIENTS AND
      METHODS: We have evaluated the efficiency of these two techniques to detect
      chromosomal abnormalities by screening 400 amniotic fluids or chorionic villi
      samples obtained from pregnant women presenting a high risk of chromosomal
      aneuploidy. RESULTS: We have found four trisomies 21, one trisomy 13, one
      monosomy 13, one trisomy 18, two triploidies, one trisomy X and one Klinefelter
      syndrome. DISCUSSION AND CONCLUSION: In our study we have detected by molecular
      biology, in less than 48 h, 100% of common chromosomal aneuploidies without false
      positive or false negative results which could lead molecular biology as a method
      of choice for the rapid detection of common aneuploidies in addition to fetal
      karyotyping.

PMID- 19574082
TI  - Ultrasonic assisted dyeing: dyeing of acrylic fabrics C.I. Astrazon Basic Red 5BL
      200%.
AB  - The dyeing of acrylic fabrics using C.I. Astrazon Basic Red 5BL 200% has been
      studied with both conventional and ultrasonic techniques. The effect of dye
      concentration, dye bath pH, ultrasonic power, dyeing time and temperature were
      studied and the resulting shades obtained by dyeing with both techniques were
      compared. Colour strength values obtained were found to be higher with ultrasonic
      than with conventional heating. The results of fastness properties of the dyed
      fabrics were studied. X-ray and Scanning Electron Microscope SEM were carried out
      on dyed samples using both methods of dyeing to find out an explanation for the
      better dyeability of acrylic fabrics with (US) method. Dyeing kinetics of acrylic
      fabrics using C.I. Astrazon Basic Red 5BL 200% using conventional and ultrasonic
      conditions were compared. The time/dye-uptake isotherms are revealing the
      enhanced dye-uptake in the second phase of dyeing. The values of dyeing rate
      constant, half-time of dyeing and standard affinity and ultrasonic efficiency
      have been calculated and discussed.

PMID- 19574083
TI  - Influence of ultrasonication and Fenton oxidation pre-treatment on rheological
      characteristics of wastewater sludge.
AB  - The effect of ultrasonication and Fenton oxidation as physico-chemical pre
      treatment processes on the change of rheology of wastewater sludge was
      investigated in this study. Pre-treated and raw sludges displayed non-Newtonian
      rheological behaviour with shear thinning as well as thixotropic properties for
      total solids ranging from 10 g/L to 40 g/L. The rheological models, namely,
      Bingham plastic, Casson law, NCA/CMA Casson, IPC Paste, and power law were also
      studied to characterize flow of raw and pre-treated sludges. Among all
      rheological models, the power law was more prominent in describing the rheology
      of the sludges. Pre-treatment processes resulted in a decrease in
      pseudoplasticity of sludge due to the decrease in consistency index K varying
      from 42.4 to 1188, 25.6 to 620.4 and 52.5 to 317.9; and increase in flow
      behaviour index n changing from 0.5 to 0.35, 0.62 to 0.55 and 0.63 to 0.58, for
      RS, UlS and FS, respectively at solids concentration 10-40 g/L. The correlation
      between improvement of biodegradability and dewaterability, decrease in
      viscosity, and change in particle size as a function of sludge pre-treatment
      process was also investigated. Fenton oxidation facilitated sludge filterability
      resulting in capillary suction time values which were approximately 50% of the
      raw sludges, whereas ultrasonication with high input energy deteriorated the
      filterability. Biodegradability was also enhanced by the pre-treatment processes
      and the maximum value was obtained (64%, 77% and 73% for raw, ultrasonicated and
      Fenton oxidized sludges, respectively) at total solids concentration of 25 g/L.
      Hence, pre-treatment of wastewater sludge modified the rheological properties so
      that: (1) the flowability of sludge was improved for transport through the
      treatment train (via pipes and pumps); (2) the dewaterability of wastewater
      sludge was enhanced for eventual disposal and; (3) the assimilation of nutrients
      by microorganisms for further value-addition was increased.

PMID- 19574084
TI  - Histopathological analysis of skeletal muscle in patients with Parkinson's
      disease and 'dropped head'/'bent spine' syndrome.
AB  - BACKGROUND: 'Dropped head' and 'bent spine' phenomena are recognized clinical
      presentations of neuromuscular disorders. Similar symptoms are known in patients
      with parkinsonian syndromes, but their pathophysiology remains unclear. One
      hypothesis is a relation between the movement disorder and the skeletal muscle
      pathology. METHODS: We describe detailed histopathological data from 19
      consecutive skeletal muscle biopsies in patients with idiopathic Parkinson's
      disease (PD) and concomitant 'dropped head' or 'bent spine' syndrome. A
      biochemical analysis of the respiratory chain complexes was also performed, and
      clinical, electrophysiological, and imaging data were analyzed. RESULTS: The
      subjects developed neuromuscular symptoms 2.7 +/- 2.4 years after onset of PD. We
      found no correlation with the age at onset of the disease, disease duration, or
      severity. We found no evidence for dystonia nor did we find any relationship
      between their anti-parkinsonian medication, and possible drug side effects.
      Muscle biopsies were abnormal in all patients. Based on histopathological
      criteria we divided the muscle pathology into three different groups, i.e.
      necrotizing myopathy, inflammatory myopathy, and myopathy with mitochondrial
      abnormalities. Biochemical analysis of respiratory chain complexes revealed
      abnormalities in nine patients. CONCLUSIONS: 'Dropped head' and 'bent spine'
      symptoms in association with PD appear to be accompanied by a wide spectrum of
      histopathological abnormalities in skeletal muscle. A muscle biopsy should be
      performed to identify potentially treatable conditions (i.e. inflammatory
      myopathies).

PMID- 19574085
TI  - A preliminary investigation into the relationship between ocular surface
      temperature and lipid layer thickness.
AB  - The aim of this study was to establish the relationship between OST, tear film
      stability as assessed by NIBUT and subjective evaluation of the lipid layer
      thickness in a young, asymptomatic, sample group (N=29). Non-invasive tear break
      up time (NIBUT) and tear lipid layer structure were evaluated through a slit-lamp
      mounted Tearscope Plus. A self-calibrating infrared thermography camera was used
      to record two OST values (one immediately post-blink and one immediately pre the
      subsequent blink). The most common lipid layer pattern observed was the amorphous
      pattern (48.3%). Differences between post- and pre-blink OST values were observed
      (paired t-test; p<0.001). Significant differences of pre-blink OST values were
      observed between the closed marmoreal group with that from the amorphous and flow
      groups (Tukey post hoc test, p<0.05). There were no differences of NIBUT values
      between each lipid layer thickness (Kruskal-Wallis test; p=0.152). A no
      significant tendency for higher OST in eyes with increased NIBUT was observed.
      This study suggests that higher OST values could be associated with thicker tear
      lipid layer in normal subjects. The lack of significant results in relation with
      tear film stability may be due to only normal subjects were included.

PMID- 19574086
TI  - Treatment relevant target immunophenotyping of 139 salivary gland carcinomas
      (SGCs).
AB  - Salivary gland carcinomas (SGCs) are rare tumors encompassing a wide spectrum of
      histologic/biologic entities. Standard non-surgical treatments are ineffective in
      case of advanced disease. Our aim was to analyze SGCs deregulation gene profiles
      that could become target for innovative treatment options. Samples from 139
      patients with primary, recurrent and/or metastatic SGCs were investigated by
      immunohistochemistry for protein encoded by tyrosine kinases receptors (TKRs)
      i.e. c-kit, HER2, EGFR and hormonal receptors, i.e. androgen (AR), estrogen (ER)
      and progesterone receptors (PgR). In 26 cases, the HER2 immunohistochemical
      analysis was complemented by fluorescence in-situ hybridization analysis. EGFR
      was the most expressed TKRs (71%) and it was found across all histotypes. c-Kit
      expression was mainly restricted to adenoid cystic carcinoma (78%) while HER2
      expression, mostly sustained by gene amplification, correlated with salivary duct
      carcinoma (SDC) in 44% of cases and adenocarcinoma, not otherwise specified (AD,
      NOS) in 21% of cases. With respect to histogenetic classification, TKRs
      expression occurred more often in tumors derived from intercalated duct rather
      than excretory ones with the only exception of HER2. AR was found in 13% of
      samples, restricted to SDC and AD, NOS and it was co-expressed with HER2 in more
      than half of the SDC cases. ER and PgR positivity was never detected. This TK
      hormonal receptors analysis identify a histotype-specific profiles that could be
      exploited for better selecting patients for innovative treatment within
      prospective studies.

PMID- 19574087
TI  - PTEN/AKT pathway involved in histone deacetylases inhibitor induced cell growth
      inhibition and apoptosis of oral squamous cell carcinoma cells.
AB  - Histone deacetylases (HDACs) inhibitors induce cell growth arrest and apoptosis
      in a wide variety of tumor cells. The purpose of this study was to evaluate the
      effects of trichostatin A (TSA), one of the HDACs inhibitors, on proliferation
      and apoptosis of oral squamous cell carcinoma cells. Exposure of Tca83 cells
      (established from human tongue squamous cell carcinoma) to TSA resulted in cell
      growth inhibition and apoptosis in a dose-dependent manner as measured with MTT
      (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and DAPI
      (4'6'diamidino-2-phenylindole dihydrochloride) staining. Western blot showed that
      both total PTEN and membrane-bound PTEN were induced by TSA treatment, whereas
      phosphorylation level (Ser 473) of AKT was correspondingly down-regulated by TSA
      treatment. Knock-down of PTEN expression with PTEN siRNA could sufficiently block
      0.25mug/ml TSA induced inhibition of cell growth, but failed to block 0.5mug/ml
      TSA induced inhibition of cell growth and apoptosis. Moreover, induction of
      apoptosis by TSA treatment was also demonstrated by cytochrome C releasing and
      induction of caspase-3. Conclusively, the results suggested that PTEN/AKT pathway
      was involved in TSA induced cell growth inhibition and apoptosis of oral squamous
      cell carcinoma cells. HDACs inhibitors could be potential anticancer drugs for
      chemotherapy of oral squamous cell carcinoma.

PMID- 19574088
TI  - Radiotherapy is not associated with an increased rate of Second Primary Tumours
      in Oral Squamous Carcinoma: a study of 370 patients.
AB  - Oral Squamous Cell Carcinoma (OSCC) remains a public health scourge. Radiotherapy
      (RT) is a major treatment modality and has been implicated in possible formation
      of Second Primary Tumours (SPT). In a single centre retrospective study of 370
      patients with OSCCs (1967-2004) associations between RT, diagnosis of SPTs,
      median SPT diagnostic time lag, Disease Free Survival (DFS) and overall survival
      (OS) were analysed. Sixty-eight (18.4%) patients developed metachronous SPTs. Two
      hundred and twenty patients (59.3%) underwent some form of RT whilst 151 (40.7%)
      patients were not exposed to RT. No significant increased incidence of SPTs was
      demonstrated in the RT group. No significant difference in SPT diagnostic time
      lag was noted amongst the groups. This study suggests that RT is neither a risk
      for SPT induction nor increases the relative diagnostic time delay of upper aero
      digestive tract SPTs.

PMID- 19574089
TI  - Synthesis and spectroscopic studies of the charge transfer complexes of 2- and 3
      aminopyridine.
AB  - The interactions of the electron donors 2-aminopyridine (2APY) and 3
      aminopyridine (3APY) with the pi-acceptors tetracyanoethylene (TCNE), 2,3
      dichloro-5,6-dicyano-p-benzoquinone (DDQ), 2-chloro-1,3,5-trinitrobenzene (picryl
      chloride, PC), and 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) were studied
      spectrophotometrically in chloroform at room temperature. The electronic and
      infrared spectra of the formed molecular charge transfer (CT) complexes were
      recorded. Photometric titration showed that the stoichiometries of the reactions
      were fixed and depended on the nature of both the donor and the acceptor. The
      molecular structures of the CT-complexes were, however, independent of the
      position of the amino group on the pyridine ring and were formulated as
      [(APY)(TCNE)], [(APY)(DDQ)], [(APY)(PC)], and [(APY) (chloranil)]. The formation
      constants (K(CT)), charge transfer energy (E(CT)) and molar extinction
      coefficients (epsilon(CT)) of the formed CT-complexes were obtained.

PMID- 19574090
TI  - Analysis of vibrational spectra of 2 and 3-methylpiperidine based on density
      functional theory calculations.
AB  - The experimental and theoretical vibrational spectra of 2 and 3-methylpiperidine
      (abbreviated as 2-MP and 3-MP) were studied. The FT-Infrared spectra of 2-MP and
      3-MP molecules were recorded in the liquid phase. The structural and
      spectroscopic analysis of the title molecules were made by using density
      functional harmonic calculations. For the title molecules, only one form was
      found most stable structure by using B3LYP level with the 6-311G (d,p) basis set.
      Selected experimental bands were assigned and characterized based on the scaled
      theoretical wave numbers by their total energy distribution (TED).

PMID- 19574091
TI  - Toward a high-throughput auditory P300-based brain-computer interface.
AB  - OBJECTIVE: Brain-computer interface (BCI) technology can provide severely
      disabled people with non-muscular communication. For those most severely
      disabled, limitations in eye mobility or visual acuity may necessitate auditory
      BCI systems. The present study investigates the efficacy of the use of six
      environmental sounds to operate a 6x6 P300 Speller. METHODS: A two-group design
      was used to ascertain whether participants benefited from visual cues early in
      training. Group A (N=5) received only auditory stimuli during all 11 sessions,
      whereas Group AV (N=5) received simultaneous auditory and visual stimuli in
      initial sessions after which the visual stimuli were systematically removed.
      Stepwise linear discriminant analysis determined the matrix item that elicited
      the largest P300 response and thereby identified the desired choice. RESULTS:
      Online results and offline analyses showed that the two groups achieved
      equivalent accuracy. In the last session, eight of 10 participants achieved 50%
      or more, and four of these achieved 75% or more, online accuracy (2.8% accuracy
      expected by chance). Mean bit rates averaged about 2 bits/min, and maximum bit
      rates reached 5.6 bits/min. CONCLUSIONS: This study indicates that an auditory
      P300 BCI is feasible, that reasonable classification accuracy and rate of
      communication are achievable, and that the paradigm should be further evaluated
      with a group of severely disabled participants who have limited visual mobility.
      SIGNIFICANCE: With further development, this auditory P300 BCI could be of
      substantial value to severely disabled people who cannot use a visual BCI.

PMID- 19574092
TI  - Stenotrophomonas maltophilia genomes: a start-up comparison.
AB  - The whole DNA sequences of 2 Stenotrophomonas maltophilia strains isolated from
      the blood of a cancer patient (K279a) and the poplar Populus trichocarpa (R551-3)
      have been compared. The 2 chromosomes exhibit extensive synteny, but each is
      punctuated by about 40 genomic islands (GEIs), which vary in size from 3 to 70kb,
      and may encode up to about 50 proteins. A large set of smaller DNA sequences,
      encoding strain-specific 'solo' orfs, contributes to genetic heterogeneity in a
      significant manner. S. maltophilia GEIs potentially encode several proteins
      mediating interactions with the environment such as transmembrane proteins,
      haemagglutinins, components of type I and IV secretion systems, and efflux
      proteins having a role in metal and/or drug resistance. The presence of specific
      GEIs in the S. maltophilia population was monitored by PCR and slot-blot
      analyses. Data suggest that some islands are present at sites different from
      those identified in K279a and that alternative islands may be integrated at
      mapped sites.

PMID- 19574093
TI  - Personal PM10 exposure in asthmatic adults in Padova, Italy: seasonal variability
      and factors affecting individual concentrations of particulate matter.
AB  - Personal exposure to PM(10) measured in different seasons in a sample of
      asthmatic subjects living in Padova (Northern Italy) was compared with
      simultaneously measured outdoor PM(10) concentrations. The specific contribution
      of ambient PM(10) and other factors to individual exposure was evaluated in one
      of the areas of Europe with the worst air pollution. Thirty-one asthmatic
      subjects (21 non-smokers and 10 smokers) carried personal PM(10) monitors for six
      24-hr sessions, in different seasons of the year. Concomitant daily 24-hr ambient
      PM(10) concentrations were measured by air quality monitoring networks. A
      multivariate analysis was performed to identify factors explaining personal
      exposure to PM(10), using a random effect model. The analysis on the 31 subjects
      referred to a total of 155 observations. The mean personal PM(10) exposure was
      higher (range 79.3-126.1microg/m(3)) than the outdoor concentrations (range 37.3
      85.4microg/m(3)) in all seasons; and personal exposures varied less than outdoor
      PM(10) levels from one season to another. Smokers had significantly higher
      personal PM(10) concentrations than non-smokers (127.99 vs 78.8microg/m(3); T=
      5.70; p<0.001). Moderate correlations emerged between outdoor and personal PM(10)
      concentrations. The correlation improved after excluding subjects exposed to
      active or passive smoking (median Pearson's R 0.41 vs 0.26). Considering all the
      subjects, smoking was the main factor affecting personal exposure, contributing
      to 41% of the variability. Outdoor PM(10) concentrations (25%), temperature (12%)
      and season (15%) also contributed to personal PM(10) exposure. Outdoor PM(10)
      (46%), temperature (20%), season (19%) and time spent indoors (6%) were
      significantly associated with personal exposure in non-smokers. We concluded that
      it is crucial to perform personal monitoring and to evaluate the complexity of
      factors that contribute to individual PM exposure. While tobacco smoke was the
      primary source of PM(10) in all subjects, the contribution of ambient components
      was particularly relevant for the personal exposure levels of our non-smokers
      living in a highly-polluted environment.

PMID- 19574094
TI  - Bone properties in child and adolescent male hockey and soccer players.
AB  - Children and adolescents who train extensively in high-impact, weight-bearing
      activities have enhanced bone mineral density. The purpose of this study was to
      evaluate bone strength, as reflected by quantitative ultrasound (QUS, Sunlight
      Omniscence), of child (10-12 yrs old) and adolescent (14-16 yrs old) male soccer
      and hockey players in comparison with age-matched controls. The groups included
      30 child (CH) and 31 adolescent (AH) hockey players, 26 child (CS) and 30
      adolescent (AS) soccer players, as well as 34 child (CC) and 31 adolescent (AC)
      healthy, non-athletic, age-matched controls. All athletes trained at an elite
      level year-round, with no difference in training volume between groups.
      Ultrasound speed of sound (SOS) was measured at the distal-radius and mid-tibia.
      In both age groups, hockey players were the heaviest and had the highest fat-free
      mass. No differences were found among groups in total energy intake, calcium or
      vitamin D intake. Radial and tibial SOS increased with age. Hockey players had
      higher radial SOS in both age groups (children: CH:3763+/-74, CS:3736+/-77,
      CC:3721+/-88 m/s; adolescents: AH:3809+/-105, AS:3767+/-85, AC:3760+/-94 m/s).
      Tibial SOS was higher in soccer players compared with controls. In spite of the
      higher body mass and fat-free mass in hockey players, their tibial SOS was
      similar to the non-athletes in both age groups. These findings support previous
      suggestions of sport-specific effects on bone strength. However, they need to be
      corroborated with longitudinal or prospective intervention studies.

PMID- 19574095
TI  - Mortality and longevity of elite athletes.
AB  - The health benefits of leisure-time physical activity are well known, however the
      effects of engaging in competitive sports on health are uncertain. This
      literature review examines mortality and longevity of elite athletes and attempts
      to understand the association between long-term vigorous exercise training and
      survival rates. Fourteen articles of epidemiological studies were identified and
      classified by type of sport. Life expectancy, standardised mortality ratio,
      standardised proportionate mortality ratio, mortality rate, and mortality odds
      ratio for all causes of death were used to analyse mortality and longevity of
      elite athletes. It appears that elite endurance (aerobic) athletes and mixed
      sports (aerobic and anaerobic) athletes survive longer than the general
      population, as indicated by lower mortality and higher longevity. Lower
      cardiovascular disease mortality is likely the primary reason for their better
      survival rates. On the other hand, there are inconsistent results among studies
      of power (anaerobic) athletes. When elite athletes engaging in various sports are
      analysed together, their mortality is lower than that of the general population.
      In conclusion, long-term vigorous exercise training is associated with increased
      survival rates of specific groups of athletes.

PMID- 19574096
TI  - Association with physical fitness, serum hormones and sleep during a 15-day
      military field training.
AB  - The present study aimed to investigate the association between physical fitness,
      sleep duration and hormonal responses during a 15-day military field training
      (MFT). The purpose of MFT was to practice offensive manoeuvres in a countryside
      area. Nine army officers volunteered to participate, and their daily working
      routine mainly consisted of tasks in the headquarters that required on-call-duty
      at all times. Physical fitness and body composition were measured just before
      MFT. Serum testosterone (TES) and cortisol (COR) concentrations and sex-hormone
      binding globulin (SHBG) were measured before MFT, as well as 8 and 15 days after
      the beginning of MFT. Heart rate (HR) was recorded for approximately 24 h on days
      8, 11 and 15 of MFT. Based on HR responses, there was no evidence of
      cardiorespiratory strain, hormonal responses or energy deficit during MFT.
      Although the changes in hormonal concentrations were insignificant, they were
      well correlated with physical fitness (r=0.67, p=0.05). Furthermore, the TES/SHGB
      ratio decreased by 28% in subjects whose VO2max was under 44 ml kg(-1) min(-1).
      On average, subjects slept for 6.20 h per day, but the sleeping rhythm was
      disturbed due to military tasks. This diurnal sleeping time was strongly
      associated with TES/COR ratio (r=0.78, p=0.01). These results indicate that MFT
      causes very individual stress reactions, despite the low levels of physical
      strain and energy deficit. We therefore concluded that the observed hormonal
      responses were mainly due to sleep deprivation and low physical fitness.

PMID- 19574097
TI  - Normative values of hip strength in adult male association football players
      assessed by handheld dynamometry.
AB  - Chronic groin pain is a common problem in association football players. Normative
      values for the strength of hip muscles, measured in an accurate and accessible
      manner, are needed to gauge strength and inform return to play decisions in this
      group. The purpose of this study was to define normative values of hip muscle
      strength using handheld dynamometry. A series of reliable clinical tests that are
      commonly used when making return to sport decisions in athletes with chronic
      adductor related groin pain have been selected. One hundred and twenty adult male
      association football players, free from injury, were recruited. Isometric
      strength of the hip flexors and adductor muscles was measured using a handheld
      dynamometer. Mean age was 24.9 years (SD 5.9). Eighty participants (67%) had
      experienced groin pain in the past. Mean strength for dominant leg hip flexion
      was 47.3 kg (95% confidence interval 45.6-49.0), non-dominant leg hip flexion was
      42.5 kg (41.1-43.9), adduction at 0 degrees hip flexion was 35.6 kg (34.1-37.1),
      adduction at 45 degrees was 32.0 kg (30.9-33.1), and adduction at 90 degrees was
      25.5 kg (24.4-26.5). This study establishes reference ranges and predictive
      equations for maximal isometric contraction strength of the hip muscles in non
      injured adult male association football players. This information will assist
      assessment and management of an athlete's return to play following injury.

PMID- 19574098
TI  - The use of a single inertial sensor to identify stride, step, and stance
      durations of running gait.
AB  - Current developments in inertial sensor technology could enable the measurement
      of running gait outside of the traditional laboratory environment. The purpose of
      this research was to determine the level of agreement between an inertial sensor
      and infrared camera based estimates of stride, step, and stance durations across
      a range of running speeds. An inertial sensor was placed on the sacrum of 10
      elite national standard runners, and the stride, step, and stance of running gait
      were compared. A total of 504 samples were collected and the running velocities
      stratified into three equal groups of low (10-12 km/h), medium (13-15 km/h), and
      high (16-19 km/h). A single inertial sensor was found to be suitable for
      identifying stride duration with Bland-Altman limits of agreement of 95%. The
      stride data showed agreement at less than 0.02s for most limits. Agreement for
      step showed five of the eight upper and lower limits below 0.02s. The largest
      differences between both capture methods were for stance. An average bias of
      0.0008s was found and standard error ranged between 0.0004s and 0.0009s across
      all variables. The results from this research found that inertial sensors are
      suitable to measure stride, step, and stance duration, and provide the
      opportunity to measure running gait outside of the traditional laboratory.

PMID- 19574099
TI  - Engaging adolescent girls from linguistically diverse and low income backgrounds
      in school sport: a pilot randomised controlled trial.
AB  - The purpose of this study was to determine the feasibility, acceptability, and
      potential efficacy of a school-based physical activity program delivered during
      school sport time among adolescent girls from low income predominately
      linguistically diverse backgrounds in New South Wales, Australia. Using a 3
      month, 2-arm, parallel-group pilot RCT design, 38 adolescent girls (Year 11) were
      recruited to participate in the program and randomised into intervention (n=17)
      or control groups (n=21). The intervention program aimed to increase physical
      activity by improving enjoyment, physical self-perception and perceived
      competence. Baseline and follow-up (12 weeks) assessments included enjoyment of
      physical activity, physical self-perception, and objectively measured physical
      activity during school sport sessions. Process data were collected through
      observations of lessons, attendance records, and interviews with participants and
      staff. Recruitment (63%) and retention (68%) goals were less than anticipated but
      similar to other studies. Participation was higher for the intervention (72%)
      than the control (60%) group and the intervention group reported high levels of
      satisfaction with the program. At follow-up, girls in the intervention group,
      compared with the control group, showed greater improvement in their enjoyment of
      physical activity during school sport (adjusted mean difference=3.8, 95%
      Confidence Interval [CI] -2.4, 10.1; Cohen's d=0.42 standard deviation units) and
      body image (adjusted difference mean=1.0, 95% CI -0.4, 2.3; d=0.50). There was a
      smaller decline in participation in physical activity during school sport
      (adjusted mean=13.6, 95% CI -21.8, 48.9; d=0.24). This study highlights major
      barriers confronting adolescent girls' participation in school sport. Some of
      these include teacher attitudes and support, activities and programming, purpose
      and distinction, and student input. Negotiating these barriers and overcoming
      them in a school setting appears feasible with support from the entire school
      community.

PMID- 19574100
TI  - Effect of heat exposure on thermoregulation and hockey-specific response time in
      field hockey goalkeepers.
AB  - This study examined the thermoregulatory responses in field hockey goalkeepers
      during games (Part A), and assessed the effect of heat stress on hockey-specific
      response time (Part B). In Part A, core temperature (T(c)), skin temperature
      (T(sk)), body mass, fluid consumption and heart rate (HR) responses of six
      goalkeepers during two premier level club games in the Western Australian
      (winter) hockey season were recorded. Part B assessed the same measures, plus a
      response time test on four goalkeepers playing a simulated game inside a climate
      chamber in cool (COOL: 20 degrees C, 40% RH) and hot (HOT: 35 degrees C, 40% RH)
      conditions. In Part A, the mean (+/-SD) T(c) and T(sk) measured in games was
      38.49+/-0.20 degrees C and 34.99+/-0.99 degrees C, with increases from baseline
      of 1.34+/-0.19 degrees C and 1.08+/-0.30 degrees C, respectively. Most of the
      increase in T(c) resulted from the pre-game warm-up. In Part B, T(c) and T(sk)
      only increased significantly (p<0.05) from baseline in the HOT condition (0.62+/
      0.18 degrees C and 1.61+/-0.82 degrees C, respectively). Response time was
      significantly slower (0.87+/-0.14s, p<0.01) after heat exposure, compared to COOL
      (0.75+/-0.15s), but the number of correct responses was not affected. For optimal
      performance, careful attention should be given to strategies to limit T(c)
      increases in field hockey goalkeepers during matches.

PMID- 19574101
TI  - Anti-inflammatory drugs, antioxidants, and prostate cancer prevention.
AB  - Prostate cancer may be the most common preventable cancer among men in the United
      States (US) and the rest of the developed world. Emerging insights into the
      molecular pathogenesis of prostate cancer suggest that damage to the prostate
      epithelium, potentially inflicted by a variety of exposures, triggers
      procarcinogenic inflammatory processes to promote disease development. In this
      milieu, the damaged epithelium may generate proliferative inflammatory atrophy
      (PIA) lesions, which may progress to prostatic intraepithelial neoplasia (PIN) or
      to prostate cancer. To attenuate prostatic carcinogenesis driven by chronic or
      recurrent prostate inflammation, rational chemoprevention has thus far featured
      anti-inflammatory drugs and antioxidants. Results from clinical trials of these
      approaches have been mixed, emphasizing the need for mechanistic studies of the
      contribution of inflammation to prostatic carcinogenesis, more extensive analyses
      of the pharmacology, including distribution of drugs into target tissue, and,
      rational development of biomarkers to identify patients that are most likely to
      respond to anti-inflammatory drugs and antioxidants (targeted chemoprevention),
      alone, or in combination (combination chemoprevention).

PMID- 19574103
TI  - Re: The early history of endoscopic correction of vesicoureteric reflux: the
      Dublin contribution.

PMID- 19574102
TI  - Effects of audio relaxation programs for blood pressure reduction in older
      adults.
AB  - BACKGROUND: Stress management is one element of the lifestyle modification that
      is recommended for blood pressure control. Reduction in sympathetic arousal may
      be achieved through a series of audio relaxation training. AIMS: The purpose of
      this study was to evaluate the short-term and long-term effects of two audio
      relaxation programs for blood pressure reduction in older adults. METHODS: This
      clinical randomized study consists of 12-sessions of intervention, with one-month
      and three-month follow up measures. 41 older adults were randomly assigned to
      either listening to a 12-minute audio relaxation program or a 12-minute Mozart
      andante. At each session, blood pressures were recorded. RESULTS: For both
      groups, the reduction in systolic and diastolic blood pressures after the 12
      session intervention training was statistically and clinically significant. The
      reduction in systolic blood pressure was greater in the audio relaxation group
      than the Mozart group. The adherence to the program at one-month and three-month
      was 54% and 66% respectively. The blood pressure at one-month and three-month
      were not significantly different than the initial measurement. CONCLUSIONS:
      Significant blood pressure reduction can be achieved through a brief 12-minute
      audio relaxation program with older adults. Guided relaxation may be more
      effective in lowering blood pressure than plain music.

PMID- 19574104
TI  - Correction of penile torsion by mobilization of urethral plate and urethra.
AB  - OBJECTIVE: To assess the feasibility of correction of torsion by mobilization of
      the urethral plate with the corpus spongiosum and the proximal urethra. PATIENTS
      AND METHODS: Of 27 cases of congenital penile torsion, 18 had hypospadias, seven
      were chordee without hypospadias, and two were isolated penile torsion. Age of
      patients varied from 2 to 26 years (mean 6 years, 8 months). Correction of
      torsion was performed: (1) penile skin de-gloving; (2) mobilization of the
      urethral plate with the corpus spongiosum up to the corona; (3) mobilization of
      the proximal urethra up to the perineum; and (4) mobilization of the hypoplastic
      urethra/urethral plate into the glans. Tubularized incised plate urethroplasty
      with spongioplasty was done in cases of hypospadias, as compared to spongioplasty
      alone in cases of chordee without hypospadias. RESULTS: Degree of torsion varied
      from 45 to 180 degrees (mean 68.70); 74% of the patients had left and 26% had
      right penile torsion. Correction of torsion was possible by penile de-gloving
      (4%), mobilization of urethral plate and spongiosum (26%), mobilization of
      proximal urethra (22%), and mobilization of urethral plate/hypoplastic urethra
      with spongiosum into glans (48%). CONCLUSIONS: Extended urethral mobilization
      corrected penile torsion in almost all cases. The technique is simple, safe,
      reproducible and effective for correction of both torsion and chordee.

PMID- 19574105
TI  - Use of polyetheretherketone spacer and recombinant human bone morphogenetic
      protein-2 in the cervical spine: a radiographic analysis.
AB  - BACKGROUND CONTEXT: Results recently reported in the literature have raised some
      concerns regarding the use of recombinant human bone morphogenetic protein (rhBMP
      2) in the cervical spine. PURPOSE: We undertook a radiological and clinical
      review of cervical fusions performed at our institution with polyetheretherketone
      (PEEK) interbody cage and rhBMP-2. STUDY DESIGN: Observational study. PATIENT
      SAMPLE: Perioperative clinical and radiologic data of all patients who underwent
      an anterior cervical discectomy and fusion using PEEK and rhBMP-2 for cervical
      spondylotic radiculopathy or myelopathy were collected. OUTCOME MEASURES: Images
      were examined for fusion, heterotopic ossification, end-plate resorption,
      subsidence, and segmental sagittal alignment. METHODS: All patients underwent
      detailed postoperative radiologic analysis using a computed tomography (CT) scan
      obtained at least 6 months postoperatively and plain X-rays obtained at regular
      intervals. RESULTS: Twenty-two patients had 38 levels fused using PEEK and
      varying doses of rhBMP-2. No anterior cervical swelling requiring additional
      procedures or longer than anticipated hospital stays occurred. Pseudoarthrosis,
      shown as a horizontal radiolucent fissure through the midportion of the PEEK cage
      on CT, occurred in four patients. Excessive bone growth into the spinal canal or
      foramina occurred in 26 (68%) patients but did not result in neurologic sequelae.
      Cystic regions in the core of the PEEK spacer were seen in most patients, with 15
      levels (39%) having cysts measuring 3mm or greater. Moderate or severe osteolysis
      of the end plates occurred in 57% of levels, and this led to subsidence of the
      construct and loss of some of the segmental sagittal alignment (ie, lordosis)
      that had been achieved with surgery. CONCLUSIONS: The unlimited supply of PEEK
      spacers and rhBMP-2 and their ease of use make them attractive platforms to
      achieve fusion. This study has demonstrated that the fusion process using rhBMP-2
      is a dynamic one, with osteolysis dominating the initial phase, leading to end
      plate resorption and consequently loss of some of the disc space height and
      sagittal alignment that was achieved with surgery. There is a high incidence of
      bone growth beyond the core of the PEEK spacer and cystic regions within the
      cage. Given our experience, we currently reserve the use of PEEK and rhBMP-2 for
      use in those patients who are at greatest risk of pseudoarthrosis.

PMID- 19574106
TI  - Low back pain in 1,100 Iranian pregnant women: prevalence and risk factors.
AB  - BACKGROUND: Low back pain (LBP) is a common and costly problem in pregnancy. It
      is one of the main reasons for disability, absence from work, and responsible for
      huge direct and indirect economical impact. PURPOSE: The purpose of this study
      was to determine the prevalence and risk factors of LBP during pregnancy. STUDY
      DESIGN: A cross-sectional study was carried out on Iranian pregnant women.
      PATIENT SAMPLE: Eleven hundred randomly selected pregnant women. OUTCOME
      MEASURES: A structured questionnaire including demographic, lifestyle, as well as
      prevalence and characteristics of LBP was used. Visual Analog Scale and Oswestry
      low back disability questionnaires were also used to assess the pain intensity
      and functional disability, respectively. METHODS: After ethical approval from
      Medical Ethics Board at the Mazandaran University of Medical Sciences and Health
      Services, a cross-sectional study was conducted on 1,100 pregnant women from 18
      health centers in Sari district, at northern Iran. RESULTS: Point, last-month,
      last 6-month, last-year, and lifetime prevalence of LBP were 40.2%, 55.9%, 59.4%,
      76.2%, and 84.1%, respectively. Prolonged standing and rest were found to be the
      most significant aggravating and relieving factors (76.3% and 87.7%,
      respectively). LBP was significantly correlated with history of previous LBP and
      LBP in previous pregnancy (p=.000 in both cases). CONCLUSION: The prevalence of
      LBP in pregnant women appears to be high and future research should focus on
      different preventive strategies during pregnancy.

PMID- 19574107
TI  - Understanding inconsistencies in patient-reported outcomes after spine treatment:
      response shift phenomena.
AB  - BACKGROUND CONTEXT: Not uncommonly, spine surgeons and physiatrists note a
      mismatch between patient-reported outcome measures, where one measure might
      indicate a good outcome and another indicates an inferior outcome after spine
      treatment. This may be the result of patient characteristics that lead to changes
      in internal standards, values, and conceptualization of their own health-related
      quality of life. This can result in a "moving goal post" when a self-report
      outcome measure is used for prepost comparisons. These "response shifts" may
      obfuscate relevant changes of interest to clinicians and are meaningful and
      worthy of study in and of themselves. PURPOSE: To provide a background on
      response shift with an emphasis on distinctions relevant to spinal interventions,
      both surgical and nonsurgical. To describe current methods for detecting and
      investigating response shift phenomena, and to propose specific hypotheses that
      can be tested in collaborative research. METHODS AND RESULTS: Two types of
      methods will be briefly described: methods that require new data collection; and
      methods that use recent statistical and technical advances to implement secondary
      analysis of existing data. Two specific testable hypotheses for spinal disorders
      are suggested along with suggested methods for testing these hypotheses.
      CONCLUSIONS: A response shift will cause the patient to use the same functional
      outcome report measure differently pre- and posttreatment. Response shift
      phenomena are likely to affect the measurement properties of standard spine
      outcome measures and to obfuscate differences between treatments in clinical
      trials and cost-effectiveness studies. They point to a need for developing
      strategies in clinical practice to manage response shifts so that they enhance
      patient well-being.

PMID- 19574108
TI  - Misleading citations in letters to the editor.

PMID- 19574109
TI  - The role of chronic atrial stretch and atrial fibrillation on posterior left
      atrial wall conduction.
AB  - BACKGROUND: The posterior left atrium (LA) is involved in the initiation and
      maintenance of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was
      to compare conduction patterns on the posterior LA in patients with mitral
      regurgitation (MR), with and without AF. METHODS: Epicardial mapping of the
      posterior LA was performed in 23 patients undergoing cardiac surgery. Patients
      were included in one of three groups: Group A-patients in sinus rhythm with
      normal left ventricular function undergoing coronary artery bypass grafting,
      Group B-patients in sinus rhythm with MR undergoing mitral valve surgery, or
      Group C-patients in persistent AF with MR undergoing mitral valve surgery.
      Conduction patterns, regional conduction velocity, conduction heterogeneity,
      conduction anisotropy, and complex fractionated atrial electrograms (CFAEs) were
      assessed. RESULTS: LA diameter was greater in patients in Groups C (57 +/- 4mm)
      and B (54 +/- 6mm) than in Group A (39 +/- 7 mm, P <0.01). Patients in Group C
      had a greater number of lines of conduction delay than Groups A and B (2.0 +/-
      0.8 vs 1 +/- 0 and 1 +/- 0, P <0.05). The extent of conduction delay and
      conduction heterogeneity was greater in Group C than in Group B, which was
      greater than in Group A (P <0.05). The percentage of CFAEs that remained stable
      during AF was 61% +/- 17%. There was a significant correlation between CFAEs
      during AF and regions of slow conduction during pacing (R = 0.36, P <0.001).
      CONCLUSION: Patients with MR, LA enlargement, and AF have more extensive regions
      of conduction slowing in the posterior LA. Anatomically constant lines of
      conduction delay in this region lead to circuitous wavefront propagation. During
      persistent AF, fractionated electrograms in the posterior LA are distributed to
      regions demonstrating slow conduction, and the majority remain stable over time.

PMID- 19574110
TI  - Effect of size and protein environment on electrochemical properties of gold
      nanoparticles on carbon electrodes.
AB  - We studied the electrochemical properties of gold nanoparticles (GNPs) and their
      complexes with proteins using square-wave voltammetry. Effect of the nanoparticle
      size and detection procedure was explored upon the oxidation of GNPs on a glassy
      carbon electrode (GCE). For pre-characterized GNPs of 13, 35 and 78 nm diameter,
      the oxidation peak potential was +0.98, +1.03 and +1.06 V vs. Ag/AgCl,
      respectively. The conjugation of GNPs with four different proteins was verified
      by UV-Vis spectroscopy and atomic force microscopy indicated the formation of
      protein shells around GNPs. This process hampered the oxidation of GNPs on bare
      GCE causing pronounced decrease in the current response by an average factor of
      72. GCE modification with carbon nanotubes weakly influenced the sensitivity of
      GNP detection but resulted in a 14.5-fold signal increase averaged for all GNP
      protein complexes. The acidic dissolution and electrodeposition of GNPs or their
      complexes adsorbed on GCE allowed superior signal amplification directly
      proportional to nanoparticle size. The results are useful for the optimization of
      voltammetric analysis of GNP-protein complexes and can be extended to the
      characterization of other metal nanostructures and their complexes with
      biological components.

PMID- 19574111
TI  - Rapid and easy method for monitoring oxidative stress markers in body fluids of
      patients with asbestos or silica-induced lung diseases.
AB  - Sensitive assay method was developed for a parallel, rapid and precise
      determination of the most prominent oxidative stress biomarkers: 8-iso
      prostaglandin F(2alpha), malondialdehyde and 4-hydroxynonenal. The method
      consisted of a pre-treatment part a solid-phase extraction, for rapid and
      effective isolation of biomarkers from body fluids (exhaled breath condensate,
      plasma and urine) and the detection method LC-ESI-MS/MS, where the selected
      reaction monitoring mode was used for its extremely high degree of selectivity
      and the stable-isotope-dilution assay for its high precision of quantification.
      The developed method was characterized by the following parameters: the
      imprecision was below 14.3%, the mean inaccuracy was determined to be lower than
      13.1%. The method was tested on samples obtained from patients diagnosed with
      asbestosis, pleural hyalinosis or silicosis, i.e. occupational lung diseases
      caused by fibrogenic dusts, inducing oxidative stress in the respiratory system,
      and then compared to samples from healthy subjects. The difference in
      concentration levels of biomarkers between the two groups was perceptible in all
      the body fluids (the difference observed in an exhaled breath condensate was
      statistically most significant).

PMID- 19574112
TI  - Avoiding duodenal endoscopic biopsies in celiac disease: are we going forward or
      looking to the past?

PMID- 19574113
TI  - Comment on: How do we interpret an elevated carbohydrate antigen 19-9 level in
      asymptomatic subjects?

PMID- 19574114
TI  - Beneficial effects and reversion of vascular lesions by thalidomide in a patient
      with bleeding portal hypertensive enteropathy.

PMID- 19574115
TI  - Men's ratings of physical attractiveness, health, and partner suitability
      simultaneously versus separately: Does it matter whether within- or between
      subjects designs are used?
AB  - Previous studies have documented moderate-to-large associations between ratings
      of physical attractiveness and other interpersonal traits, but this research has
      invariably relied on within-subjects designs that leave open the possibility of
      halo effects or response biases. In the present study, 40 men completed the
      Photographic Figure Rating Scale in a within-subjects design, rating the figures
      for physical attractiveness, health, and suitability as a long-term partner. In
      addition, 108 men completed the same scale in a between-subjects design, being
      randomly allocated to one of three subgroups where they rated the figures for
      attractiveness, health, or suitability as a long-term partner. Results indicated
      no significant differences in ratings for the within-subjects participants. In
      contrast, there were significant differences in ratings for the between-subjects
      design. These results highlight the importance of considering halo and response
      bias effects when designing studies of interpersonal judgements and interpreting
      their results.

PMID- 19574116
TI  - Inferior gluteal artery myocutaneous island transposition flap reconstruction of
      irradiated perineal defects.
AB  - BACKGROUND: With the progressive use of more radical surgical resections and pre
      operative chemo-radiotherapy for locally advanced anorectal cancers, there has
      become an increasing need for reconstructive options that import well
      vascularised tissue of sufficient bulk to the perineum. We present our technique
      of inferior gluteal artery myocutaneous (IGAM) transposition flaps for
      reconstruction after extended abdomino-perineal excision (APE) for anorectal
      cancer. METHODS: Six consecutive male patients with T2/T3 rectal carcinoma
      underwent neoadjuvant chemo-radiotherapy followed by extended APE and immediate
      reconstruction with an islanded IGAM transposition flap. The operative technique
      and surgical outcomes were assessed with follow-up ranging from 3 to 18 months
      (median 5 months). RESULTS: In all cases, there were clear histological margins
      with no flap failures or partial flap losses, and no post-operative hernias.
      There were no major wound complications, with only one superficial breakdown
      associated with high body mass index (BMI) and adhesive tape allergy, treated
      with dressings alone. There was no donor site morbidity evident following flap
      harvest. CONCLUSION: The IGAM island transposition flap provides excellent tissue
      bulk, a large reliable skin paddle and a long pedicle that permits flexible
      positioning with tension free closure. Our successful results and high patient
      satisfaction make it a favourable option that should be considered when faced
      with this reconstructive challenge.

PMID- 19574117
TI  - Anchor-shaped nasal framework designed for total nasal reconstruction.
AB  - BACKGROUND: Nasal frame grafting has been widely used in nasal reconstruction;
      however, a stable nasal frame with satisfactory functional and aesthetic results
      is hard to achieve in total nasal reconstruction. In this study, we devised a
      technique to create an individually designed anchor-shaped nasal frame composed
      of an L-strut and two C-battens, and applied it in the total nasal reconstruction
      procedure to achieve satisfactory functional and aesthetic results. METHOD: In a
      9-year period, 17 patients with total nasal defect were treated with autogenous
      costal grafting utilising forehead flap as the covering. The techniques of the
      individualised design of the anchor-shaped nasal frame were applied to fit the
      facial features. All cases were followed for at least 18 months, and outcomes
      were evaluated separately by the patients and plastic surgeons in terms of
      aesthetics, stability and function. RESULTS: Satisfactory results were achieved
      in most of the cases after the operation. More than 82.4% of the patients in this
      series were assessed as satisfactory by both groups in the aesthetics survey;
      more than 76.5% in the stability survey; and more than 64.7% in the function
      survey. Complications included flap hyperpigmentation (one case), flap-skin
      paleness (one case), L-strut distortion (three cases) and stuffiness of the
      nostrils (one case) as well as minor brow elevation of the donor side (five
      cases). CONCLUSIONS: The procedure of applying individually designed anchor
      shaped nasal frame with forehead flap technique has obvious advantages for
      restoration of distinct and delicate subunits, stable nasal structure and good
      nasal function.

PMID- 19574118
TI  - Tunable features of magnetoelectric transformers.
AB  - We have found that magnetostrictive FeBSiC alloy ribbons laminated with
      piezoelectric Pb(Zr,Ti)O(3) fiber can act as a tunable transformer when driven
      under resonant conditions. These composites were also found to exhibit the
      strongest resonant magnetoelectric voltage coefficient of 750 V/cm-Oe. The
      tunable features were achieved by applying small dc magnetic biases of -5 <or=
      H(dc) <or= 5 Oe. The features include 1) a high voltage gain of -55 <or= V(gain)
      <or= 55; and 2) a large current-to-voltage conversion of -2000 <or=alpha(I-V)
      <or= 2000 (V/A). The tunable transformer features can be attributed to large
      changes in the piezomagnetic coefficient and permeability of the magnetostrictive
      phase under H(dc).

PMID- 19574119
TI  - Highly efficient damage-free correction of thickness distribution of quartz
      crystal wafers by atmospheric pressure plasma etching.
AB  - A new finishing method was developed to correct the thickness distribution of a
      quartz crystal wafer by the numerically controlled scanning of a localized
      atmospheric pressure plasma. The thickness uniformity level of a commercially
      available AT-cut quartz crystal wafer was improved to less than 50 nm without any
      subsurface damage by applying one correction process. Furthermore, applying a
      pulse-modulated plasma markedly decreased the correction time of the thickness
      distribution without breaking the quartz crystal wafer by thermal stress.

PMID- 19574120
TI  - Piezoelectric-electrostrictive monolithic bi-layer composite flextensional
      actuator.
AB  - We propose a new type of flextensional actuator comprised of an
      electromechanically active element which is a piezoelectric-electrostrictive
      monolithic bi-layer composite (PE-MBLC) capped by truncated thin brass sheets.
      The PE-MBLC contains equal amounts of 0.65[Pb(Mg(1/3)Nb(2/3))O(3)]-0.35PbTiO(3)
      and 0.9[Pb(Mg(1/3)Nb(2/3))O(3)]-0.1PbTiO(3) by volume, and is obtained by a co
      sintering process. With applied E(max) = 10 kV/cm unipolar drive, the maximum
      axial displacement (u(33)) produced by the uncapped and capped PE-MBLC is 11 and
      21 microm, respectively. The hysteresis in unipolar u(33) at 0.5 E(max) is 4.6%
      for the uncapped PE-MBLC, while that for the capped one is 11%. Under bipolar
      excitation, the maximum u(33) for uncapped is 11.6 microm at +E(max) and 6.6
      microm at +E(max) with an asymmetry factor (zeta) of 1.75 for which u(33) < 0 for
      all E < 0. Under bipolar excitation, the maximum u(33) at +E(max) for the capped
      PE-MBLC is 19 microm while that for -E(max) is 8 microm with zeta = 2.4, for
      which u(33) > 0 at -E(max) but is smaller than the u(33) at +E(max). The origins
      of the observed asymmetry in u(33) are discussed in the context of symmetry
      superposition and deformation mechanics of the endcaps.

PMID- 19574121
TI  - Pressure sensitivity of the vapor-cell atomic clock.
AB  - Although atomic clocks have very low levels of frequency instability, they are
      nonetheless sensitive (albeit slightly) to various environmental parameters,
      including temperature, power supply voltage, and dc magnetic fields. In the
      terrestrial environment, however, atmospheric pressure (i.e., the air's molecular
      density) is not generally included in this list, because the air's density
      variations near the surface of the earth will typically have a negligible effect
      on the clock's performance. The situation is different, however, for clocks
      onboard satellites like Galileo, where manufacturing and testing are done at
      atmospheric pressure, while operation is in vacuum. The pressure sensitivity of
      atomic clocks, in particular vapor-cell atomic clocks, can therefore be of
      significance. Here, we discuss some of the ways in which changes in atmospheric
      pressure affect vapor-cell atomic clocks, and we demonstrate that, for one
      device, the pressure-sensitivity traces back to a pressure-induced change in the
      temperature of the clock's filter and resonance cells.

PMID- 19574122
TI  - Temperature mapping near the surface of ultrasound transducers using
      susceptibility- compensated magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI)-based temperature mapping very close to the
      surface of an ultrasound transducer is not possible due to the large magnetic
      susceptibility- induced image artifacts that arise from the materials used in
      transducer construction. Here, it is shown in phantoms that "susceptibility
      compensated" MRI sequences can be used to measure thermal increases approximately
      1 mm from the surface of a 4-element cymbal array transducer, which has been used
      widely for noninvasive transdermal drug delivery. The estimated temperatures
      agree well with those measured using thermocouples.

PMID- 19574123
TI  - Pulse subtraction time delay imaging method for ultrasound contrast agent
      detection.
AB  - Detection of contrast agent in perfused tissues has been an important research
      topic for many years. Currently available methods are mostly based on the strong
      nonlinear scattering of contrast agent microbubbles. These methods selectively
      extract those parts of the spectrum that show the largest difference in
      nonlinearity between contrast agent and tissue. The method introduced in this
      paper expands this extraction approach in that it additionally exploits
      differences in system behavior between tissue and contrast bubbles. The resonant
      nature of contrast bubbles implies that the response of a contrast bubble is
      stateful, i.e., the response not only depends on the current input, but also on
      all previous inputs. Tissue does not show this dependence on previous inputs. Our
      method is based on a 3 pulse design in which the echoes from 2 nonoverlapping
      pulses are subtracted from a third pulse. With this method we aim to separate and
      suppress those parts in an echo signal that originate from tissue while leaving
      the part originating from contrast bubbles relatively undisturbed. Simulation
      results show increases up to 30 dB in contrast-to-tissue ratio (CTR) with this
      method relative to single pulse echoes. This was confirmed in an in vitro
      experiment that showed an increase of approximately 12 dB in CTR.

PMID- 19574124
TI  - Fast ultrasound imaging simulation in K-space.
AB  - Most available ultrasound imaging simulation methods are based on the spatial
      impulse response approach. The execution speed of such a simulation is of the
      order of days for one heart-sized frame using desktop computers. For some
      applications, the accuracy of such rigorous simulation approaches is not
      necessary. This work outlines a much faster 3-D ultrasound imaging simulation
      approach that can be applied to tasks like simulating 3-D ultrasound images for
      speckletracking. The increased speed of the proposed simulation method is based
      primarily on the approximation that the point spread function is set to be
      spatially invariant, which is a reasonably good approximation when using polar
      coordinates for simulating images from phased arrays with constant aperture.
      Ultrasound images are found as the convolution of the PSF and an object of
      sparsely distributed scatterers. The scatterers are passed through an anti
      aliasing filter before insertion into a regular beam-space grid to reduce the
      bandwidth and significantly reduce the amount of data. A comparison with the well
      established simulation software package Field II has been made. A simulation of a
      cyst image using the same input object was found to be in the order of 7000 times
      slower than the presented method. Following these considerations, the proposed
      simulation method can be a rapid and valuable tool for working with 3-D
      ultrasound imaging and in particular 3-D speckle-tracking.

PMID- 19574125
TI  - Robust finite impulse response beamforming applied to medical ultrasound.
AB  - We previously described a beamformer architecture that replaces the single
      apodization weights on each receive channel with channel-unique finite impulse
      response (FIR) filters. The filter weights are designed to optimize the contrast
      resolution performance of the imaging system. Although the FIR beamformer offers
      significant gains in contrast resolution, the beamformer suffers from low
      sensitivity, and its performance rapidly degrades in the presence of noise. In
      this paper, a new method is presented to improve the robustness of the FIR
      beamformer to electronic noise as well as variation or uncertainty in the array
      response. A method is also described that controls the sidelobe levels of the FIR
      beamformer's spatial response by applying an arbitrary weighting function in the
      filter design algorithm. The robust FIR beamformer is analyzed using a
      generalized cystic resolution metric that quantifies a beamformer's clinical
      imaging performance as a function of cyst size and channel input SNR. Fundamental
      performance limits are compared between 2 robust FIR beamformers - the dynamic
      focus FIR (DF-FIR) beamformer and the group focus FIR (GF-FIR) beamformer - the
      conventional delay-and-sum (DAS) beamformer, and the spatial-matched filter (SMF)
      beamformer. Results from this study show that the new DF- and GF-FIR beamformers
      are more robust to electronic noise compared with the optimal contrast resolution
      FIR beamformer. Furthermore, the added robustness comes with only a slight loss
      in cystic resolution. Results from the generalized cystic resolution metric show
      that a 9-tap robust FIR beamformer outperforms the SMF and DAS beamformer until
      receive channel input SNR drops below -5 dB, whereas the 9-tap optimal contrast
      resolution beamformer's performance deteriorates around 50 dB SNR. The effects of
      moderate phase aberrations, characterized by an a priori root-mean-square
      strength of 28 ns and an a priori full-width at half-maximum correlation length
      of 3.6 mm, are investigate- d on the robust FIR beamformers. Full sets of robust
      FIR beamformer filter weights are constructed using an in silico model scanner
      and the L14-5/38 mm probe. Using the derived weights, a series of simulated point
      target and anechoic cyst B-mode images are generated to investigate further the
      potential increases in contrast resolution when using the robust FIR beamformers.
      Under the investigated conditions, the 7-tap optimal contrast resolution
      beamformer and the 7-tap robust beamformer with added SNR constraint increase
      lesion detectability by 247 and 137% compared with the conventional DAS
      beamformer, respectively. Finally, experimental phantom and in vivo images are
      produced using this novel receive architecture. The simulated and experimental
      images clearly show a reduction in clutter and an increase in contrast resolution
      compared with the conventionally beamformed images. This novel receive beamformer
      can be applied to any conventional ultrasound system where the system response is
      reasonably well characterized.

PMID- 19574126
TI  - In vitro and in vivo brain ablation created by high-intensity focused ultrasound
      and monitored by MRI.
AB  - In this paper, magnetic resonance imaging (MRI) is investigated for monitoring
      small and large lesions created by high-intensity focused ultrasound (HIFU) in
      freshly excised lamb brain and in rabbit brain in vivo. A single-element
      spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating
      at 1 MHz was used. A prototype MRI-compatible positioning device that is used to
      navigate the transducer is described. The effects of HIFU were investigated using
      T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery
      (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than
      T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for
      both thermal and bubbly lesions. The best contrast between lesion and brain with
      T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best
      contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio
      (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the
      corresponding CNR was approximately 12. With this system, we were able to create
      large lesions (by producing overlapping lesions), and it was possible to monitor
      these lesions with MRI with excellent contrast. The length of the lesions in vivo
      brain was much higher than the length in vitro, indicating that the penetration
      in the in vitro brain is limited, possibly by reflection due to trapped bubbles
      in the blood vessels. This paper demonstrates that HIFU has the potential to
      treat brain tumors in humans. This could be done either using a single-element
      transducer with a frequency around 1 MHZ or using a multi-element transducer.

PMID- 19574127
TI  - Contrast agent response to chirp reversal: simulations, optical observations, and
      acoustical verification.
AB  - Active response of a microbubble is characterized by its resonance behavior where
      the microbubble might oscillate after the excitation waveform has been turned
      off. We investigate in this paper an excitation approach based on this resonance
      phenomenon using chirps. The technique, called chirp reversal, consists in
      transmitting a first excitation signal, the up-sweep chirp (UPF) of increasing
      frequency with time, and a second excitation signal, the down-sweep (DNF) that is
      a replica of the first signal, but time reversed with a sweep of decreasing
      frequency with time. Simulations using a modified Rayleigh-Plesset equation were
      carried out to determine bubble response to chirp reversal. In addition, optical
      observations and acoustical measurements were carried out to corroborate the
      theoretical findings. Results of simulations show differences between bubbles'
      oscillations in response to up-sweep and down-sweep chirps mainly for transmitted
      center frequencies above the bubble's resonance frequency. Bubbles that are at
      resonance or far away from resonance engender identical responses. From the
      optical data, the larger bubbles showed different dynamics when up-sweep or down
      sweep chirps were transmitted. Smaller bubbles (< 2 microm diameter) appear to be
      less sensitive to frequency sweep at 1.7 MHz center frequency. However, driven at
      a higher center frequency, smaller bubbles tend to be more sensitive. These
      results were confirmed through the acoustical measurements. We concluded that
      simulations and experimental data show that significant differences might be
      observed between bubbles' responses to UPF and DNF chirps. We demonstrate in this
      study that, for an optimal use of chirp reversal, the transmit frequency should
      be higher than the resonance frequency of the contrast microbubbles.

PMID- 19574128
TI  - Air-coupled ultrasonic spectroscopy of highly damping materials using pulse
      compression.
AB  - Air-coupled ultrasonic spectroscopy is described, whereby the output from a pulse
      compression system is used. It is demonstrated that the cross-correlation
      operation used within a pulse-compression system preserves amplitude and phase
      information. This approach allows the signal-to-noise ratio and, hence, signal
      detection capability to be improved by the cross-correlation, while allowing
      noncontact spectral information for solid samples to be obtained. Results are
      presented for chocolate samples, where measurements of interest to the food
      industry have been obtained.

PMID- 19574130
TI  - Models of ultrasonic wave propagation in epoxy materials.
AB  - This paper is concerned with modeling ultrasonic wave propagation in epoxy
      materials to better understand NDE procedures and to provide reliable input to
      more complex models of guided wave propagation in layered structures. Different
      physical models are considered in the context of how well they simulate the
      (known) linear relationship between bulk wave attenuation coefficients and
      frequency. The identified models are then extended to simulate wave propagation
      in materials with mechanical properties, which vary gradually in the spatial
      dimension. This is achieved using electric circuit transmission line analogs to
      the viscoelastic mechanical system. Verifying experimental results are included.

PMID- 19574129
TI  - Integrated high-temperature piezoelectric plate acoustic wave transducers using
      mode conversion.
AB  - Piezoelectric thick (>66 microm) films have been directly coated onto aluminum
      (Al) substrates using a sol-gel spray technique. With top electrode, these films
      serve as integrated ultrasonic transducers (IUT), which normally operate as
      thickness longitudinal wave transducers. When such IUT are located at the edges
      of the metallic plates, they can excite and detect symmetrical, antisymmetric and
      shear horizontal types of plate acoustic waves (PAW) using mode conversion
      methods. In 2 mm thick Al plates, 2 line defects of 1 mm width and 1 mm depth
      were clearly detected at temperatures up to 150 degrees C in pulse-echo mode.
      Results indicated that, for 2 mm thick aluminum plates, shear horizontal PAW were
      the best for the line defect detection. Also, the experimental results agree well
      with those obtained by a finite-difference-based method.

PMID- 19574131
TI  - A circular cylindrical, radially polarized ceramic shell piezoelectric
      transformer.
AB  - We propose a circular cylindrical shell piezoelectric transformer of radially
      polarized ceramics operating in thickness-stretch modes. Two theoretical analyses
      involving different approximations are performed on the proposed transformer
      using the 3-D equations of linear piezoelectricity. The transforming ratio, input
      admittance, and efficiency of the transformer are calculated and compared with
      those of a previously analyzed circular cylindrical shell transformer of axially
      polarized ceramics operating in shear modes.

PMID- 19574132
TI  - Surface acoustic wave properties of (100) AlN films on diamond with different IDT
      positions.
AB  - (100) AlN films have better surface acoustic wave (SAW) properties than (002) AlN
      films. In this research, (100) AlN films were combined with diamonds as a new
      composite SAW substrate. The SAW properties of (100) AlN films on diamonds were
      analyzed with 4 composite structures: interdigital transducer (IDT)/(100)
      AlN/diamond, (100) AlN/IDT/diamond, IDT/(100) AlN/metal/diamond, and
      metal/IDT/(100) AlN/diamond, and they exhibited some excellent SAW properties.
      Our research results provide a predictable and theoretical basis for further
      application on high-velocity SAW devices.

PMID- 19574133
TI  - Real-time volume imaging using a crossed electrode array.
AB  - This paper describes a unique crossed electrode array for real-time volume
      ultrasound imaging. By placing orthogonal linear array electrode patterns on the
      opposite sides of a hemispherically shaped composite transducer substrate, a 2-D
      array can be fabricated using a small fraction of the elements required for a
      traditional 2-D array. The performance of the array is investigated using a
      computer simulation of the radiation pattern. We show that by using a 288-element
      crossed electrode pattern it is possible to collect large field of view volume
      images (60 degrees x 60 degrees sector) at real-time frame rates (>20 volume
      images/s), with image contrast and resolution comparable to what can be obtained
      using a conventional 128-element linear phased array.

PMID- 19574134
TI  - Hardware-efficient realization of a real-time ultrasonic target detection system
      using IIR filters.
AB  - In this study, we address the increased computational demands of a frequency
      diverse ultrasonic target detection system by developing a zero-phase IIR (ZP
      IIR) filter. Several ZP-IIR filter types including Chebyshev-I, Chebyshev- II,
      and Butterworth were analyzed for their detection performance. The 4th-order
      filters with 8-bit quantized coefficients are shown to improve the flaw-to
      clutter ratio by approximately 10 dB. Furthermore, the reduced adder graph
      algorithm is used for a hardware realization of ZP-IIR filters that does not
      require any dedicated multipliers. A small number of coefficients inherent to IIR
      filters and their multiplierless implementation provide efficient architecture
      suitable for compact, real-time ultrasonic imaging devices.

PMID- 19574136
TI  - Estimator for reflective delay line-type SAW sensors.
AB  - This correspondence presents an estimator for reflective delay line-type surface
      acoustic wave (SAW) sensors. The estimator is derived from an analytical model
      and its range of validity is discussed. The proposed estimator enables
      simultaneous access to several SAW sensors with time-orthogonal responses and it
      can be implemented in a computationally efficient way utilizing the fast Fourier
      transform algorithm. The estimator is experimentally verified and its performance
      is compared with that of a reference estimator.

PMID- 19574135
TI  - Dual-electrode CMUT with non-uniform membranes for high electromechanical
      coupling coefficient and high bandwidth operation.
AB  - In this paper, we report measurement results on dual-electrode CMUT demonstrating
      electromechanical coupling coefficient (k(2)) of 0.82 at 90% of collapse voltage
      as well as 136% 3 dB one-way fractional bandwidth at the transducer surface
      around the design frequency of 8 MHz. These results are within 5% of the
      predictions of the finite element simulations. The large bandwidth is achieved
      mainly by utilizing a non-uniform membrane, introducing center mass to the
      design, whereas the dual-electrode structure provides high coupling coefficient
      in a large dc bias range without collapsing the membrane. In addition, the non
      uniform membrane structure improves the transmit sensitivity of the dual
      electrode CMUT by about 2dB as compared with a dual electrode CMUT with uniform
      membrane.

PMID- 19574137
TI  - The investigation of localized sound generation using two ultrasound beams.
AB  - A quantitative analysis of the effects of difference frequency, source
      separation, and crossing angle on the generated scattered difference frequency
      sound fields is presented to evaluate the feasibility of localized sound
      production using 2 uniform pistons. Nonlinear crossed beam experiments were also
      carried out in an anechoic chamber. Experimental results show that the audible
      sound could be generated within the interaction region defined by the overlap
      volume of 2 ultrasonic beams.

PMID- 19574141
TI  - Structure and ferroelectric properties of Bi(Zn(1/2)Ti(1/2))O3
      (Bi(1/2)K(1/2))TiO3 perovskite solid solutions.
AB  - Lead-free piezoelectric ceramics based on chiBi(Zn(1/2)Ti(1/2))O3-(1
      chi)(Bi(1/2)K(1/2))TiO3 were obtained via solid state processing techniques. A
      single perovskite phase with tetragonal symmetry was obtained for
      Bi(Zn(1/2)Ti(1/2))O3 (BZT) substitutions up to 20 mol%. The maximum density was
      97.1% at the composition of chi = 0.1. The dielectric measurement indicated that
      the transition temperature decreased linearly with increasing BZT content. The P
      E loops revealed an increase in remanent polarization (P(r)) with the addition of
      BZT. The maximum planar coupling coefficient, kappa(p), for the chi = 0.1
      composition was 21.6 and the piezoelectric coefficient, d33, for chi = 0, chi =
      0.05, and chi = 0.1 was 108, 185, and 235 pm/V, respectively. Overall, the
      dielectric and piezoelectric properties showed significant improvement when BZT
      was added.

PMID- 19574140
TI  - 3-D ultrasound guidance of autonomous robot for location of ferrous shrapnel.
AB  - Vibrations can be induced in ferromagnetic shrapnel by a variable electromagnet.
      Real time 3-D color Doppler ultrasound located the induced motion in a needle
      fragment and determined its 3-D position in the scanner coordinates. This
      information was used to guide a robot which moved a probe to touch the shrapnel
      fragment.

PMID- 19574142
TI  - Analyses of power output of piezoelectric energy-harvesting devices directly
      connected to a load resistor using a coupled piezoelectric-circuit finite element
      method.
AB  - This paper presents, for the first time, a coupled piezoelectric-circuit finite
      element model (CPC-FEM) to analyze the power output of a vibration-based
      piezoelectric energy-harvesting device (EHD) when it is connected to a load
      resistor. Special focus is given to the effect of the load resistor value on the
      vibrational amplitude of the piezoelectric EHD, and thus on the current, voltage,
      and power generated by the device, which are normally assumed to be independent
      of the load resistor value to reduce the complexity of modeling and simulation.
      The presented CPC-FEM uses a cantilever with a sandwich structure and a seismic
      mass attached to the tip to study the following characteristics of the EHD as a
      result of changing the load resistor value: 1) the electric outputs: the current
      through and voltage across the load resistor; 2) the power dissipated by the load
      resistor; 3) the displacement amplitude of the tip of the cantilever; and 4) the
      shift in the resonant frequency of the device. It is found that these
      characteristics of the EHD have a significant dependence on the load resistor
      value, rather than being independent of it as is assumed in most literature. The
      CPC-FEM is capable of predicting the generated output power of the EHD with
      different load resistor values while simultaneously calculating the effect of the
      load resistor value on the displacement amplitude of the tip of the cantilever.
      This makes the CPC-FEM invaluable for validating the performance of a designed
      EHD before it is fabricated and tested, thereby reducing the recurring costs
      associated with repeat fabrication and trials. In addition, the proposed CPC-FEM
      can also be used for producing an optimized design for maximum power output.

PMID- 19574143
TI  - Switching atomic fountain clock microwave interrogation signal and high
      resolution phase measurements.
AB  - This paper focuses on the development of tools aiming to solve several problems
      related to the microwave interrogation signal in atomic fountains. We first
      consider the problem related to cycle synchronous phase transients caused by the
      sequential operation of the atomic fountain. To search for such systematic phase
      variations deeply buried in the microwave synthesizer phase noise, we have
      developed a novel triggered-phase transient analyzer capable of processing the
      microwave signal to extract the phase in a synchronous manner even in the
      presence of frequency modulation. With this device we check in vivo the LNE-SYRTE
      fountain's interrogation signals with a resolution approaching 1 microradian. In
      addition, using this device, we investigate an innovative approach to solve a
      second problem, namely, the shift caused by microwave leakage in the fountain.
      Our approach consists of switching off the fountain microwave interrogation
      signal when atoms are outside the microwave cavity. To do that, we have developed
      a switch that is almost free of phase transients and is thus able to eliminate
      the frequency shift caused by microwave leakage without inducing significant
      phase transients on the interrogation signal.

PMID- 19574144
TI  - An ultrasonic imaging speckle-suppression and contrast-enhancement technique by
      means of frequency compounding and coded excitation.
AB  - A method for improving the contrast resolution of B-mode images is proposed by
      combining the speckle-reduction technique of frequency compounding (FC) and the
      coded excitation and pulse-compression technique called resolution enhancement
      compression (REC). FC suppresses speckle but at the expense of a reduction in
      axial resolution. Using REC, the axial resolution and bandwidth of the imaging
      system was doubled. Therefore, by combining REC with FC (REC-FC), the tradeoff
      between axial resolution and contrast enhancement was extended significantly.
      Simulations and experimental measurements were conducted with a single-element
      transducer (f/2.66) having a center frequency of 2.25 MHz and a -3-dB bandwidth
      of 50%. Simulations and measurements of hyperechoic (+6 dB) tissue-mimicking
      targets were imaged. Four FC cases were evaluated: full-, half-, third-, and
      fourth-width of the true impulse response bandwidth. The image quality metrics
      used to compare REC-FC to conventional pulsing (CP) and CP-FC were contrast-to
      noise ratio (CNR), speckle signal-to-noise ratio, histogram pixel intensity, and
      lesion signal-to-noise ratio. Increases in CNR of 121%, 231%, 302%, and 391% were
      obtained in experiments when comparing REC-FC for the full-, half-, third-, and
      fourth-width cases to CP. Furthermore, smaller increases in CNR of 112%, 233%,
      and 309% were obtained in experiments when comparing CP-FC for the half-, third-,
      and fourth-width cases to CP. Improved lesion detectability was observed by using
      REC-FC.

PMID- 19574145
TI  - Synthetic transmit beam technique in an aberrating environment.
AB  - Parallel beamforming is a commonly used method for increasing the frame rate in
      ultrasound imaging systems. By receiving in several directions for each
      transmission, the frame rate is increased. However, this method also introduces
      blocklike artifacts in the B-mode image, due to the reception offsets when
      compared with the transmission direction. The synthetic transmit beam technique
      (STB) has been previously proposed as a compensation technique when addressing
      these artifacts. Previous work by Hergum et al. investigated the performance of
      this method in regard to the case of 2 parallel beams in tissue mimicking
      phantoms without aberrations. This study is a continuation of that work in which
      this method is tested in an aberrating environment using 4 parallel beams.
      Several quantitative and qualitative performance aspects of this method have been
      investigated such as lateral shift invariance, beam-to-beam correlation
      fluctuations, speckle- tracking performance, improvements from higher order STB
      interpolation and beam profile shape preservation, as well as perceived image
      quality improvements. The results were obtained from simulations, in vivo
      measurements, and in vitro measurements. The results showed that aberration
      amplified the image artifacts for regular parallel beamforming, which resulted in
      more shift variance, lower beam-to-beam correlation, higher speckle- tracking
      error, and more variation in beam profile shape. Compared with regular parallel
      beamforming, STB resulted in a significantly better image quality and a higher
      score in all measuring methods. The improvements from using STB were largest in
      cases involving aberration. Using STB, the variation in beam-to-beam correlation
      was reduced from 30% to 1%, and the standard deviation of the speckle-tracking
      error was reduced from 8% to 1.5%.

PMID- 19574146
TI  - Acoustic imaging of thick biological tissue.
AB  - Up to now, biomedical imaging with ultrasound for observing a cellular tissue
      structure has been limited to very thinly sliced tissue at very high ultrasonic
      frequencies, i.e., 1 GHz. In this paper, we present the results of a systematic
      study to use a 150 to 200 MHz frequency range for thickly sliced biological
      tissue. A mechanical scanning reflection acoustic microscope (SAM) was used for
      obtaining horizontal cross-sectional images (C-scans) showing cellular
      structures. In the study, sectioned specimens of human breast cancer and tissues
      from the small intestine were prepared and examined. Some accessories for
      biomedical application were integrated into our SAM (Sonix HS-1000 and Olympus UH
      3), which operated in pulse-wave and tone-burst wave modes, respectively. We
      found that the frequency 100 to 200 MHz provides optimal balance between
      resolution and penetration depth for examining the thickly sliced specimens. The
      images obtained with the lens focused at different depths revealed cellular
      structures whose morphology was very similar to that seen in the thinly sectioned
      specimens with optical and scanning acoustic microscopy. The SAM operation in the
      pulse-echo mode permits the imaging of tissue structure at the surface, and it
      also opens up the potential for attenuation imaging representing reflection from
      the substrate behind the thick specimen. We present such images of breast cancer
      proving the method's applicability to overall tumor detection. SAM with a high
      frequency tone-burst ultrasonic wave reveals details of tissue structure, and
      both methods may serve as additional diagnostic tools in a hospital environment.

PMID- 19574147
TI  - Reduced peak-hopping artifacts in ultrasonic strain estimation using the Viterbi
      algorithm.
AB  - Internal strain resulting from tissue deformation can be estimated by correlation
      processing of speckle patterns within complex (i.e., radio frequency) ultrasound
      images acquired during deformation. At large deformations, the magnitude of the
      correlation coefficient peak can be significantly lower than unity, so that
      random speckle correlations will exceed the true peak. This effect is called
      "peak hopping" and causes significant errors in displacement and deformation
      estimates. Here we investigate the Viterbi algorithm, a dynamic programming
      procedure, to overcome peak-hopping artifacts by finding the most likely sequence
      of hidden states in a sequence of observed events. It is well suited to motion
      estimation in elasticity-imaging studies because adjacent tissue elements remain
      adjacent following deformation. Particularly, tissue elements along an ultrasonic
      beam in one image lie along a 3-D continuous curve in the next image instant. The
      observed event in this case is the correlation coefficient of a pixel at a
      certain displacement. Radio-frequency data were generated before and after
      deformation with an average strain of 6%. Simulations were performed for a
      homogenous medium and for a medium with a stiffer inclusion. Results show that
      Viterbi processing of speckle-tracking outputs can significantly reduce peak
      hopping artifacts.

PMID- 19574148
TI  - Phase rotation methods in filtering correlation coefficients for ultrasound
      speckle tracking.
AB  - In speckle-tracking-based myocardial strain imaging, large interframe/volume peak
      systolic strains cause peak hopping artifacts separating the highest correlation
      coefficient peak from the true peak. A correlation coefficient filter was
      previously designed to minimize peak hopping artifacts. For large strains,
      however, the correlation coefficient filter must follow the strain distribution
      to remove peak hopping effectively. This processing usually means interpolation
      and high computational load. To reduce the computational burden, a narrow band
      approximation using phase rotation is developed in this paper to facilitate
      correlation coefficient filtering. Correlation coefficients are first phase
      rotated to increase coherence, then filtered. Rotated phase angles are determined
      by the local strain and spatial position. This form of correlation coefficient
      filtering enhances true correlation coefficient peaks in large strain
      applications if decorrelation due to deformation does not completely destroy the
      coherence among neighboring correlation coefficients. The assumed strain used in
      the filter can also deviate from the true strain and still be effective. Further
      improvement in displacement estimation can be expected by combining correlation
      coefficient filtering with a new Viterbi-based displacement estimator.

PMID- 19574149
TI  - Effects of ultrasound frequency, temporal sampling frequency, and spatial
      sampling step on the quantitative ultrasound parameters of articular cartilage.
AB  - Quantitative ultrasound imaging may provide a technique for diagnosing initial
      signs of osteoarthritis (OA), such as surface fibrillation of articular
      cartilage. Because subchondral sclerosis and osteophyte formation occur in OA as
      well, ultrasonic analysis of subchondral bone could yield useful diagnostic
      information. In this study, we investigated whether low-frequency (5 MHz)
      ultrasound, typically used in bone diagnostics, would be feasible for evaluating
      the integrity of the surface of the cartilage. The reflection parameters in the
      time and frequency domains, the ultrasound roughness index, and the wavelet-based
      parameters were evaluated using ultrasound transducers operating at 5, 10, and 50
      MHz frequencies. The effects of variable size of spatial sampling steps and of
      temporal sampling frequencies were also investigated. Custom-made phantoms and
      cartilage samples with various surface characteristics were analyzed. The
      reflection parameters detected the surface degradation with all ultrasound
      frequencies. The roughness of the surface could only be evaluated reliably with
      the 50 MHz-focused transducer. In conclusion, simultaneous analysis of the
      reflection parameters of the cartilage and the subchondral bone is feasible at
      low (5 MHz) ultrasound frequencies. However, reliable evaluation of the
      microtopography of the cartilage requires use of a higher ultrasound frequency.

PMID- 19574150
TI  - Prospective ECG-gated mouse cardiac imaging with a 34-MHz annular array
      transducer.
AB  - Prospective imaging with electrocardiogram (ECG) and respiratory gating presents
      an imaging application that leverages the improved image quality of high
      frequency (>20 MHz) annular arrays without the need for rapid mechanical motion.
      The limitation of prospective imaging is that the object being imaged must have a
      periodically stable motion. The present study investigated the implementation of
      prospective imaging with a 34 MHz annular-array scan system to image the mouse
      heart at high effective frame rates, >200 frames/s (fps). M-mode data for all
      transmit-to-receive pairs were acquired at a series of spatial locations using
      ECG and respiratory gating, and the data were then synthetically focused in
      postprocessing. The pulse-repetition frequency of the M-mode data determined the
      effective frame rate of the final B-mode image sequence. The hearts of adult mice
      were prospectively imaged and compared with retrospective data acquired with a
      commercial ultrasonic biomicroscope (UBM). The annular array data were acquired
      at an effective frame rate of 500 fps spanning 0.5 s, and the UBM data were
      acquired at 1000 fps spanning 0.15 s. The resulting images showed that multiple
      heart cycles could be clearly resolved using prospective imaging and that
      synthetic focusing improved image resolution and SNR of the right ventricle,
      interventricular septum, posterior edge of the left ventricle (LV), and papillary
      muscles of the LV versus fixed-focused imaging and the retrospective imaging of
      the UBM machine.

PMID- 19574152
TI  - Numerical model of longitudinal wave scattering in polycrystals.
AB  - The scattering of elastic waves in polycrystalline materials is relevant for
      ultrasonic materials characterization and nondestructive evaluation (NDE).
      Ultrasonic attenuation is used widely to extract microstructural parameters such
      as grain size. Accurate interpretation of experimental data requires robust
      scattering models. Such models typically assume constant density, uniform grain
      size, and ergodicity hypotheses. The accuracy and limits of applicability of
      these models cannot be fully tested with experiments due to practical limits of
      real materials processing. Here, this problem is examined in terms of numerical
      simulations using Voronoi polycrystals that are discretized using finite
      elements. Wave propagation is studied by integrating the system directly in time
      using a plane strain formulation. Voronoi polycrystals with cubic symmetry and
      random orientations are used making the bulk material statistically isotropic.
      Example numerical results for materials with various degrees of scattering that
      are of common interest are presented. The numerical results are presented and
      compared with scattering theory for a wide range of frequencies. The numerical
      results show good agreement with the theory for the examples examined with
      evidence that the correlation function is frequency dependent. These results are
      anticipated to impact ultrasonic NDE of polycrystalline media.

PMID- 19574151
TI  - Measurement of viscoelastic properties of tissue-mimicking material using
      longitudinal wave excitation.
AB  - This paper presents an experimental framework for the measurement of the
      viscoelastic properties of tissue-mimicking material. The novelty of the
      presented framework is in the use of longitudinal wave excitation and the study
      of the longitudinal wave patterns in finite media for the measurement of the
      viscoelastic properties. Ultrasound is used to track the longitudinal motions
      inside a test block. The viscoelastic parameters of the block are then estimated
      by 2 methods: a wavelength measurement method and a model fitting method.
      Connections are also made with shear elastography. The viscoelastic parameters
      are estimated for several homogeneous phantom blocks. The results from the new
      methods are compared with the conventional rheometry results.

PMID- 19574153
TI  - Sensing a buried resonant object by single-channel time reversal.
AB  - Scaled laboratory experiments are conducted to assess the efficacy of iterative,
      single-channel time reversal for enhancement of monostatic returns from resonant
      spheres in the free field and buried in a sediment phantom. Experiments are
      performed in a water tank using a broad-band piston transducer operating between
      0.4 and 1.5 MHz and calibrated using free surface reflections. Solid and hollow
      metallic spheres, 6.35 mm in diameter, are buried in a consolidation of 128
      microm-mean- diameter spherical glass beads. The procedure consists of exciting
      the target object with a broadband pulse, sampling the return using a finite time
      window, reversing the signal in time, and using this reversed signal as the
      source waveform for the next interrogation. Results indicate that the spectrum of
      the returns rapidly converges to the dominant mode in the backscattering response
      of the target. Signal-to-noise enhancement of the target echo is demonstrated for
      a target at several burial depths. Images generated by scanning the transducer
      over the location of multiple buried targets demonstrate the ability of the
      technique to distinguish between targets of differing type and to yield an
      enhancement of different modes within the response of a single target as a
      function of transducer position and processing bandwidth.

PMID- 19574154
TI  - A performance study of a laser Doppler vibrometer for measuring waveforms from
      piezoelectric transducers.
AB  - The stresses at transducer contacts were estimated from accurate particle
      velocity measurements by using a laser Doppler vibrometer (LDV). We then
      evaluated the performance of LDV for ultrasonic waveform measurements in physical
      model experiments that are employed for modeling seismic observations. For such
      experiments, the characteristics of the source and detector should be exactly
      known. Disc-shaped compression and shear-mode piezoelectric transducers were
      attached on a flat surface of a steel semicircular column, and ultrasonic waves
      were excited by single-shot sine waves with 0.25, 0.5, and 1 MHz frequencies.
      Radial and transverse components were measured by LDV at a distance of 150 mm
      from the source. The maximum amplitudes of waves with respect to radiation angle
      give a radiation pattern of a transducer. Each observed radiation pattern was
      fitted to the calculated radiation pattern by assuming a harmonically oscillating
      stress distributed uniformly on a flat circular area. The observed radiation
      patterns show fairly good agreement with the calculated radiation patterns for
      both radial and transverse components when the source frequencies are 0.25 and
      0.5 MHz. Because the best-fit stress values were independently estimated from the
      radial and the transverse radiation patterns, the 2 stress values should be equal
      for each source and frequency. The discrepancy between the estimated radial and
      transverse stress values becomes larger as the source frequency increases.
      Provided that coincidence of the 2 stress values indicates the validity of
      waveform measurements, the results suggest that LDV is applicable for measuring
      the 3-D particle-velocity at frequencies up to 0.5 MHz.

PMID- 19574155
TI  - Design of narrow bandwidth ladder-type filters with sharp transition bands using
      mutually connected resonator elements.
AB  - This paper proposes a new design technique for a ladder-type filter to reduce the
      passband width without sacrificing the insertion loss, out-of-band rejection, and
      steepness of the transition bands. First, it is shown that 2 transmission zeros
      can be generated by connecting an additional resonator in either series or
      parallel arm of the ladder filter topology. This new filter topology can be
      designed systematically by the derived-m transformation. Second, it is
      demonstrated that the narrow bandwidth, sharp transition bands, and large out-of-
      band rejection are simultaneously realized by applying the present technique to
      specifically designed ladder-type filters. Finally, this technique is applied to
      the design of a SAW filter fabricated on the Cu-grating/15 degrees YX-LiNbO3
      structure.

PMID- 19574156
TI  - Development of a low-frequency high purity A0 mode transducer for SHM
      applications.
AB  - The reliability of structural health monitoring (SHM) systems based on guided
      ultrasonic waves is improved if pure modes are generated by the transducers. A
      piezoelectric- based transducer generating high purity A0 mode guided waves at
      low frequencies (around 20 kHz) was developed. The through-thickness resonance of
      a piezoelectric element was lowered to the frequency region of interest by use of
      backing masses and low-stiffness front layers. Soft front layers also reduced
      significantly the transmission of in-plane displacements caused by Poisson's
      ratio effects in the piezoelectric element to the structure. Parametric studies
      were undertaken by varying the backing mass length, the transducer diameter, and
      the thickness of the front layer. The thickness of the plates on which the
      transducers were operated was found to be a critical issue and these effects were
      evaluated. Results obtained by finite-element analysis were validated by
      experimental measurements and showed that signals with A0/S0 energy ratios
      substantially above 40 dB can be obtained.

PMID- 19574157
TI  - Optimization of a circular thin-film piezoelectric actuator lying on a clamped
      multilayered elastic plate.
AB  - A system consisting of a circular multilayered thin-film elastic plate and a
      piezoelectric actuator, which is generally used for ultrasound generation in air,
      is studied in this paper. Effects of the electrode dimension of a circular thin
      film piezoelectric actuator lying on a clamped multilayered elastic plate are
      discussed theoretically, while the first-order theory of asymmetrically laminated
      piezoelectric plates with consideration of coupled extension and flexure of the
      reference plane is used. Numerical results show that the deflection of the
      elastic plate can be optimized by adjusting the radius of the top electrode.

PMID- 19574158
TI  - The theoretical model of 1-3-2 piezocomposites.
AB  - A theoretical model is proposed to calculate the equivalent model the
      electromechanical properties of (1-3-2) piezocomposite. Piezoelectric equations
      of state were derived in terms of equivalent parameters based on linear
      electromechanical response and uniform field theories. Equivalent parameters
      (g31, g33, beta33, d31, d33, epsilon33) of 1-3-2 piezocomposite were obtained.
      The computed g31 is -19.9 x 10(-3) V x m/N(-1), g33 is 68.4 x 10(-3) V x m/N(-1),
      d31 is -98 x 10(-12) C/N, d33 is 336 x 10(-12) C/N, and epsilonT33/epsilon0 is
      555, while the volume fraction of piezoelectric phase nu1 is 0.4 and nu2 is 0.1.
      The variation of composite properties with volume fraction of piezoelectric phase
      have been modeled and experimentally verified. The computed d31, d33, and
      epsilon33 are within 12.5, 6.7, and 8.4% of experimental values, respectively.

PMID- 19574159
TI  - SU-8-based nanocomposites for acoustical matching layer.
AB  - SU-8, an epoxy-based photoresist, was introduced as the acoustical matching layer
      between silicon and water for lab-on-chip applications integrating acoustic
      characterization. Acoustical performances, including the acoustic longitudinal
      wave velocity and attenuation of the SU-8-based matching layer, were
      characterized at a frequency of 1 GHz at room temperature. The gain in echo
      characterization with a SU-8/SiO2 bilayer and with different nanocomposite
      monolayers made of SU-8 and TiO2 nanoparticles (size around 35 nm) between
      silicon and water was characterized as being above 10 dB in each case. With the
      increase of concentration of TiO2 in SU-8 based composites from 0 to 30 wt%,
      acoustical impedance of the nanocomposites increased from about 3 to 6 MRayls,
      respectively. The acoustical attenuation in the nanocomposites is between 0.5 and
      0.6 dB/microm. The most efficient matching was obtained with the nanocomposite
      integrating 30 wt% TiO2 nanoparticles, with which the enhanced loss is about 0.34
      dB as the attenuation is about 0.5 dB/microm. This type of matching layer has
      potential applications in lab-on-chip technology for high frequency transducers
      or in the fabrication of high frequency piezocomposites.

PMID- 19574160
TI  - Low-cost, high-speed back-end processing system for high-frequency ultrasound B
      mode imaging.
AB  - For real-time visualization of the mouse heart (6 to 13 beats per second), a back
      end processing system involving high-speed signal processing functions to form
      and display images has been developed. This back-end system was designed with new
      signal processing algorithms to achieve a frame rate of more than 400 images per
      second. These algorithms were implemented in a simple and cost-effective manner
      with a single field-programmable gate array (FPGA) and software programs written
      in C++. The operating speed of the back-end system was investigated by recording
      the time required for transferring an image to a personal computer. Experimental
      results showed that the back-end system is capable of producing 433 images per
      second. To evaluate the imaging performance of the back-end system, a complete
      imaging system was built. This imaging system, which consisted of a recently
      reported high-speed mechanical sector scanner assembled with the back-end system,
      was tested by imaging a wire phantom, a pig eye (in vitro), and a mouse heart (in
      vivo). It was shown that this system is capable of providing high spatial
      resolution images with fast temporal resolution.

PMID- 19574161
TI  - Graph-matching based CTA.
AB  - Separating bone, calcification, and vessels in computer tomography angiography
      (CTA) allows for a detailed diagnosis of vessel stenosis. This paper presents a
      new, graph-based technique that solves this difficult problem with high accuracy.
      The approach requires one native data set and one that is contrast enhanced. On
      each data set, an attributed level-graph is derived and both graphs are matched
      by dynamic programming to differentiate between bone, on one hand side, and
      vessel/calcification on the other hand side. Lumen and calcified regions are then
      separated by a profile technique. Evaluation is based on data from vessels of
      pelvis and lower extremities of elderly patients. Due to substantial
      calcification and motion of patients between and during the acquisitions, the
      underlying approach is tested on a class of difficult cases. Analysis requires 3
      5 min on a Pentium IV 3 GHz for a 700 MByte data set. Among 37 patients, our
      approach correctly identifies all three components in 80% of cases correctly
      compared to visual control. Critical inconsistencies with visual inspection were
      found in 6% of all cases; 70% of these inconsistencies are due to small vessels
      that have 1) a diameter near the resolution of the CT and 2) are passing next to
      bony structures. All other remaining deviations are found in an incorrect
      handling of the iliac artery since the slice thickness is near the diameter of
      this vessel and since the orientation is not in cranio-caudal direction.
      Increasing resolution is thus expected to solve many the aforementioned
      difficulties.

PMID- 19574162
TI  - Tomographic reconstruction of three-dimensional volumes using the distorted born
      iterative method.
AB  - Although real imaging problems involve objects that have variations in three
      dimensions, a majority of work examining inverse scattering methods for
      ultrasonic tomography considers 2-D imaging problems. Therefore, the study of 3-D
      inverse scattering methods is necessary for future applications of ultrasonic
      tomography. In this work, 3-D reconstructions using different arrays of
      rectangular elements focused on elevation were studied when reconstructing
      spherical imaging targets by producing a series of 2-D image slices using the 2-D
      distorted Born iterative method (DBIM). The effects of focal number f/#, speed of
      sound contrast c, and scatterer size were considered. For comparison, the 3-D
      wave equation was also inverted using point-like transducers to produce fully 3-D
      DBIM image reconstructions. In 2-D slicing, blurring in the vertical direction
      was highly correlated with the transmit/receive elevation point-spread function
      of the transducers for low c. The eventual appearance of overshoot artifacts in
      the vertical direction were observed with increasing c. These diffraction-related
      artifacts were less severe for smaller focal number values and larger spherical
      target sizes. When using 3-D DBIM, the overshoot artifacts were not observed and
      spatial resolution was improved. However, results indicate that array
      configuration in 3-D reconstructions is important for good image reconstruction.
      Practical arrays were designed and assessed for image reconstruction using 3-D
      DBIM.

PMID- 19574164
TI  - CoCRF deformable model: a geometric model driven by collaborative conditional
      random fields.
AB  - We present a hybrid framework for integrating deformable models with learning
      based classification, for image segmentation with region ambiguities. We show how
      a region-based geometric model is coupled with conditional random fields (CRF) in
      a simple graphical model, such that the model evolution is driven by a
      dynamically updated probability field. We define the model shape with the signed
      distance function, while we formulate the internal energy with a C(1) continuity
      constraint, a shape prior, and a term that forces the zero level of the shape
      function towards a connected form. The latter can be seen as a term that forces
      different closed curves on the image plane to merge, and, therefore, our model
      inherently carries the property of merging regions. We calculate the image
      likelihood that drives the evolution using a collaborative formulation of
      conditional random fields (CoCRF), which is updated during the evolution in an
      online learning manner. The CoCRF infers class posteriors to regions with feature
      ambiguities by assessing the joint appearance of neighboring sites, and using the
      classification confidence to regulate the inference. The novelties of our
      approach are (i) the tight coupling of deformable models with classification,
      combining the estimation of smooth region boundaries with the robustness of the
      probabilistic region classification, (ii) the handling of feature variations, by
      updating the region statistics in an online learning manner, and (iii) the
      improvement of the region classification using our CoCRF. We demonstrate the
      performance of our method in a variety of images with clutter, region
      inhomogeneities, boundary ambiguities, and complex textures, from the zebra and
      cheetah examples to medical images.

PMID- 19574163
TI  - Motor protein function in skeletal muscle-a multiple scale approach to
      contractility.
AB  - We present an approach to skeletal muscle contractility and its regulation over
      different scales ranging from biomechanical studies in intact muscle fibers down
      to the motility and interaction of single motor protein molecules. At each scale,
      shortening velocities as a measure for weak cross-bridge cycling rates are
      extracted and compared. Experimental approaches include transmitted light
      microscopy, second harmonic generation imaging of contracting myofibrils, and
      fluorescence microscopy of single molecule motility. Each method yields image
      sequences that are analyzed with automated image processing algorithms to extract
      the contraction velocity. Using this approach, we show how to isolate the
      contribution of the motor proteins actin and myosin and their modulation by
      regulatory proteins from the concerted action of electro-mechanical activation on
      a more complex cellular scale. The advantage of this approach is that averaged
      contraction velocities can be determined on the different scales ranging from
      isolated motor proteins to sarcomere levels in myofibrils and myofibril arrays
      within the cellular architecture. Our results show that maximum shortening
      velocities during in situ electrical activation of sarcomere contraction in
      intact single muscle cells can substantially deviate from sliding velocities
      obtained in oriented in vitro motility assays of isolated motor proteins showing
      that biophysical contraction kinetics not simply translate linearly between
      contractility scales. To adequately resolve the very fast initial mechanical
      activation kinetics of shortening at each scale, it was necessary to implement
      high-speed imaging techniques. In the case of intact fibers and single molecule
      motility, we achieved a major increase in temporal resolution up to frame rates
      of 200-1000 fps using CMOS image sensor technology. The data we obtained at this
      unprecedented temporal resolution and the parameters extracted can be used to
      validate results obtained from computational models of motor protein interaction
      and skeletal muscle contractility in health and muscle disease. Our approach is
      feasible to explain the possible underlying mechanisms that contribute to
      different shortening velocities at different scales and complexities.

PMID- 19574165
TI  - Eigendecomposition of images correlated on S(1), S(2), and SO3 using spectral
      theory.
AB  - Eigendecomposition represents one computationally efficient approach for dealing
      with object detection and pose estimation, as well as other vision-based
      problems, and has been applied to sets of correlated images for this purpose. The
      major drawback in using eigendecomposition is the off line computational expense
      incurred by computing the desired subspace. This off line expense increases
      drastically as the number of correlated images becomes large (which is the case
      when doing fully general 3-D pose estimation). Previous work has shown that for
      data correlated on S(1), Fourier analysis can help reduce the computational
      burden of this off line expense. This paper presents a method for extending this
      technique to data correlated on S(2) as well as SO3 by sampling the sphere
      appropriately. An algorithm is then developed for reducing the off line
      computational burden associated with computing the eigenspace by exploiting the
      spectral information of this spherical data set using spherical harmonics and
      Wigner-D functions. Experimental results are presented to compare the proposed
      algorithm to the true eigendecomposition, as well as assess the computational
      savings.

PMID- 19574166
TI  - A genome-wide association study primer for clinicians.
AB  - Genome-wide association studies (GWAS) use high-throughput genotyping technology
      to relate hundreds of thousands of genetic markers (genotypes) to clinical
      conditions and measurable traits (phenotypes). This review is intended to serve
      as an introduction to GWAS for clinicians, to allow them to better appreciate the
      value and limitations of GWAS for genotype-disease association studies. The input
      of clinicians is vital for GWAS, since disease heterogeneity is frequently a
      confounding factor that can only really be solved by clinicians. For diseases
      that are difficult to diagnose, clinicians should ensure that the cases do indeed
      have the disease; for common diseases, clinicians should ensure that the controls
      are truly disease-free.

PMID- 19574168
TI  - Ruptured corpus luteum with hemoperitoneum: case characteristics and demographic
      changes over time.
AB  - OBJECTIVE: Women of reproductive age are at risk of ruptured corpus luteum with
      hemoperitoneum. We identified the clinical and demographic features of patients
      recently treated in our institution and compared the findings with those from an
      earlier series, to detect any changes in disease identity that have occurred over
      the past 20 years. MATERIALS AND METHODS: Charts of patients treated between
      January 2001 and December 2003 at Changhua Christian Hospital were reviewed.
      Clinical parameters were compared with those from our previous study in the
      1980s. RESULTS: A total of 91 women were diagnosed with ruptured corpus luteum
      and hemoperitoneum (mean age, 26 years; range, 15-42 years). Most ruptures
      (60.4%) occurred during the secretory phase and most women (57.1%) reported
      recent sexual intercourse prior to the onset of pain. Most patients (81.3%)
      required laparoscopic intervention to achieve hemostasis. No obvious differences
      were found between the results of this study and those from the 1985 series,
      except that our patients were younger, were more often unmarried, chose
      laparoscopic interventions rather than laparotomy, and that there was an emerging
      trend towards conservative treatment. CONCLUSION: The manifestations of corpus
      luteum hemorrhage in this study were similar to those observed in the 1980s at
      the same medical center. However, the demographic parameters (age, marital
      status) and the modalities of treatment (conservative treatment, mode of surgical
      interventions) had changed in line with the evolution of society, culture, and
      the progress of medical science over the past 20 years.

PMID- 19574167
TI  - Differential expression of NUDT9 at different phases of the menstrual cycle and
      in different components of normal and neoplastic human endometrium.
AB  - OBJECTIVE: The human endometrium manifests different and distinct morphologies
      and physiologies during the different phases of the menstrual cycle. We aimed to
      determine which candidate genes demonstrate differential expression patterns in
      the endometrium during different phases of the menstrual cycle. MATERIALS AND
      METHODS: Using differential display reverse transcription polymerase chain
      reaction to compare day 5 and day 18 human glandular endometrium obtained by
      laser capture microdissection, we identified a specific gene, NUDT9 (nucleoside
      diphosphate-linked moiety X motif 9). NUDT9 is known to function as a highly
      specific adenosine diphosphate ribose pyrophosphatase and has been mapped to
      chromosome 4q22.1. It gives rise to two alternatively spliced messenger RNAs,
      NUDT9alpha and NUDT9beta, encoding a member of the Nudix hydrolase family. In
      this study, we purified NUDT9 protein and produced an antibody, which we then
      used for immunohistochemical studies. RESULTS: Using this anti-NUDT9 antibody, we
      successfully demonstrated that NUDT9 protein was differentially expressed in
      endometrial glandular cells at different phases of the menstrual cycle. NUDT9 was
      also found to be expressed more prominently in the epithelial glandular component
      than in the stromal component of human endometrial carcinomas. CONCLUSION: We
      suggest that NUDT9 may be involved in the regulation of the menstrual cycle and
      may be related to the proliferation of glandular cells in the human endometrium.

PMID- 19574169
TI  - Use of 24-hour urinary protein and calcium for prediction of preeclampsia.
AB  - OBJECTIVE: To assess the efficacy of 24-hour urinary protein and calcium for the
      prediction of preeclampsia. MATERIALS AND METHODS: Two hundred normotensive women
      at 20-28 weeks' gestation were enrolled in the study. All women were asked to
      collect a 24-hour urine sample. Urinary protein and calcium were measured and
      expressed as milligrams per 24 hours. Sensitivity, specificity and predictive
      values were calculated for each test, and cutoff values were calculated using
      receiver operating characteristic curves. RESULTS: Twenty-one of the 200 women
      developed preeclampsia, including eight who developed severe preeclampsia and 13
      who developed mild preeclampsia. Compared with the normotensive women (n = 179),
      the hypertensive patients (n = 21) had significantly lower urinary calcium
      excretion (167.23 +/- 80.63 mg vs. 277.43 +/- 60.38 mg) and higher proteinuria
      (351.14 +/- 41.58 mg vs. 296.33 +/- 30.03 mg). CONCLUSION: A decrease in 24-hour
      urinary calcium and increase in protein between 20-28 weeks' gestation are risk
      factors for preeclampsia.

PMID- 19574171
TI  - Pfannenstiel versus Maylard incision for gynecologic surgery: a randomized,
      double-blind controlled trial.
AB  - OBJECTIVE: The aim of this study was to compare the effects of the transverse
      muscle-cutting Maylard incision and the Pfannenstiel incision for hysterectomies,
      in terms of postoperative complications, pain, and quality of life. MATERIALS AND
      METHODS: This randomized, double-blind study compared two laparotomy techniques.
      All hysterectomies were performed for benign conditions. Eighty cases were
      randomly assigned to receive either Pfannenstiel or Maylard incisions. Measured
      intraoperative variables included volume of blood loss and duration of surgery.
      Postoperative variables included abdominal distension, postoperative pain, and
      quality of life. RESULTS: Postoperative abdominal distension was significantly
      lower in the Maylard group (p = 0.004). There were no differences in
      intraoperative characteristics and duration of hospitalization, hemorrhage
      volume, or duration of surgery between the two groups. CONCLUSION: Hysterectomy
      performed via the Maylard incision was associated with the use of fewer
      additional analgesics than hysterectomy performed via the Pfannenstiel incision.

PMID- 19574170
TI  - Prenatal Group B Streptococcus test using real-time polymerase chain reaction.
AB  - OBJECTIVE: The aim of this study was to evaluate the percentage of pregnant women
      with negative Group B Streptococcus (GBS) screening results by culture at 35
      weeks' gestation, who subsequently had positive GBS test results after 39 weeks'
      gestation. MATERIALS AND METHODS: From 2006 to 2007, we recruited 150 pregnant
      women who received routine GBS culture screening at 35 weeks' gestation with
      negative results, and who had repeat cultures and real-time polymerase chain
      reaction (RT-PCR) tests for GBS after 39 weeks' gestation. RESULTS: Two percent
      of pregnant women with GBS-negative results by culture screening at 35 weeks'
      gestation were GBS-positive at 39 weeks' gestation. CONCLUSION: It is necessary
      to perform a GBS test 4 weeks after an initial negative GBS culture at 35-37
      weeks of gestation. RT-PCR provides a simple and rapid alternative method for
      detecting rectovaginal GBS colonization at the time of labor.

PMID- 19574172
TI  - Effects of calcium supplement therapy in women with premenstrual syndrome.
AB  - OBJECTIVE: Scientific evidence suggests that cyclic fluctuations in a variety of
      nutrients, especially calcium, may help to explain some features of premenstrual
      syndrome (PMS). We determined the efficacy of calcium supplementation in women
      suffering from PMS. MATERIALS AND METHODS: A double-blind clinical trial was
      designed to evaluate the effect of calcium supplement therapy on PMS symptoms.
      The study groups were selected from young female college students, based on PMS
      criteria. The subjects were divided in two groups; one group received placebo and
      the other received 500 mg of calcium carbonate twice daily for 3 months. The
      severity and intensity of symptoms, including early fatigability, changes in
      appetite, and depression, were evaluated using a standard questionnaire. Symptoms
      were compared before and after treatment. RESULTS: The mean age was 21.4 +/- 3.6
      years. Early tiredness, appetite changes, and depressive symptoms were
      significantly improved in the group receiving calcium treatment compared with the
      placebo group. CONCLUSION: Our results showed that calcium supplements reduced
      early fatigability, changes in appetite, and depression in women with PMS.

PMID- 19574173
TI  - Mutation-prone positions within the estrogen receptor.
AB  - OBJECTIVE: Estrogen is an important female hormone. The estrogen receptor (ER)
      plays a critical role in the development of breast cancer. Mutations within the
      ER can have clinically significant consequences. MATERIALS AND METHODS:
      Identification of sites vulnerable to mutation is a new trend aimed at extending
      our knowledge of diseases at the genomic and proteomic levels. In this study,
      bioinformatics analysis was performed to determine the positions corresponding to
      specific peptide motifs in the amino acid sequence of the ER. A new computational
      tool called GlobPlot was used to identify the weak linkage positions within the
      ER. RESULTS: The results allowed the identification of mutation-resistant
      positions. CONCLUSION: This study showed that the weak linkages within the ER
      could be identified, and these could provide the basis for further studies aimed
      at predicting possible new ER mutations.

PMID- 19574174
TI  - Use of a gonadotropin-releasing hormone agonist to manage perimenopausal women
      with symptomatic uterine myomas.
AB  - OBJECTIVE: To determine the acceptability and effectiveness of a gonadotropin
      releasing hormone (GnRH) agonist for the treatment of perimenopausal women with
      symptomatic uterine myomas. MATERIALS AND METHODS: The participants included 43
      women with symptomatic myomas who wished to retain their uteri. All the women
      were older than 45 years old, agreed to use the GnRH agonist for menopause
      induction, and were without any underlying malignancy. They were treated with six
      courses of GnRH agonist between 2004 and 2005. The definition of re-intervention
      included: (1) surgical intervention, such as hysterectomy, myomectomy or
      laparoscopic uterine vessel occlusion, or (2) modification of GnRH agonist use.
      Modification of GnRH agonist use included either failure to complete a 6-month
      GnRH agonist treatment course, or re-use of GnRH agonist with/without
      interruption of continuity. Failure was defined as women who underwent surgical
      intervention or failed to complete the 6-month GnRH agonist treatment.
      Evaluations were performed every 6 months, for up to 2 years. RESULTS: Re
      intervention rates were 14.0% (n = 6), 23.3% (n = 10) and 32.6% (n = 14), and
      failure rates were 7.0% (n = 3), 11.6% (n = 5) and 16.3% (n = 7), at the end of
      the 6-, 12- and 24-month follow-up periods, respectively. Three patients failed
      to complete the 6-month GnRH agonist treatment, and four received surgical
      interventions. CONCLUSION: More than 80% of women in this study benefited from
      the use of GnRH agonist to produce menopause, suggesting that this can be an
      alternative choice for managing perimenopausal women with symptomatic uterine
      myomas.

PMID- 19574175
TI  - Interaction between interferon regulatory factor-1 and human papillomavirus E7
      oncogene in cervical cancer: an ontology study.
AB  - OBJECTIVE: Cervical cancer is an important female malignancy. The discovery of
      human papillomavirus (HPV) as an etiologic agent of cervical cancer has prompted
      increased interest in the biology and oncogenicity of this virus. The E7 protein
      is found predominantly in the nucleus and, to a lesser extent, in the cytoplasm
      in cervical cancer cell lines. HPV E7 has been shown to be functionally
      associated with the tumor suppressor interferon regulatory factor (IRF)-1 in
      cervical carcinogenesis. MATERIALS AND METHODS: In this study, new gene ontology
      technology was used to predict changes in the molecular function and biologic
      processes caused by the interaction between IRF-1 and HPV E7. RESULTS: The
      molecular function and biologic processes of IRF-1 and the combined IRF-1 and HPV
      E7 (IRF-1-E7) were derived using the GoFigure server. The combined IRF-1-E7
      demonstrated more functions and biologic processes compared with IRF-1 alone.
      CONCLUSION: IRF-1-E7 was shown to be responsible for the positive regulation of
      many interleukins and to be involved in the differentiation of T-helper cells.

PMID- 19574177
TI  - Electroacupuncture reduces uterine artery blood flow impedance in infertile
      women.
AB  - OBJECTIVE: To evaluate the effects of electroacupuncture (EA) on pregnancy rate
      and uterine artery blood flow impedance in patients undergoing in vitro
      fertilization (IVF). MATERIALS AND METHODS: This prospective, randomized trial
      was carried out in the IVF center of China Medical University Hospital in Taiwan,
      from February 1, 2004 to January 30, 2005. A total of 44 patients were enrolled
      in the study. Of these, 30 were allocated to acupuncture, and 14 were allocated
      to no acupuncture. EA was performed four times, twice a week for 2 weeks, from
      day 2 of the study to the day before oocyte retrieval. After patients felt the
      needle reaction, the needles were attached to an electrical stimulator for 30
      minutes. Clinical pregnancy and pulsatility index (PI) of right and left uterine
      arteries before and after EA were measured. RESULTS: There was no significant
      difference in pregnancy rate between the two groups (acupuncture group, 30%; non
      acupuncture group, 28.6%). The mean PI of both uterine arteries was significantly
      reduced after EA (left uterine artery, 2.3 to 2.0; right uterine artery, 2.4 to
      2.2). There was no significant change in PI in the group with no acupuncture
      (left uterine artery, 2.5 to 2.3; right uterine artery, 2.4 to 2.3). CONCLUSION:
      EA could be useful for reducing uterine artery blood flow impedance, but did not
      increase the pregnancy rate in patients undergoing IVF.

PMID- 19574176
TI  - The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a
      pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of calcium-vitamin D
      and metformin on the menstrual cycle and ovulation in patients with polycystic
      ovary syndrome (PCOS). MATERIALS AND METHODS: In this pilot study, 60 infertile
      PCOS patients were enrolled in a randomized clinical trial and divided into three
      equal groups. Group 1 received 1,000 mg of calcium and 400 IU of vitamin D per
      day, orally. Group 2 received the same as Group 1, plus 1,500 mg/day of
      metformin. Group 3 received 1,500 mg/day of metformin. The patients were treated
      for 3 months and followed up for a further 3 months. Regularity of menses, number
      of large follicles (> or = 14 mm) and pregnancy rates were compared among the
      three groups. RESULTS: Generalized estimating equation tests showed that the
      number of dominant follicles (> or = 14 mm) during the 2-3 months of follow-up
      was higher in the calcium-vitamin D plus metformin group than in either of the
      other two groups (p = 0.03). CONCLUSION: The effects of metformin and calcium
      vitamin D in regulating the menstrual cycle suggest that they could also be
      effective for the treatment of anovulation and oligomenorrhea, with possible
      consequences for pregnancy rates in PCOS patients.

PMID- 19574178
TI  - Genome-wide detection of uniparental disomy in a fetus with intrauterine growth
      restriction using genotyping microarrays.
AB  - OBJECTIVE: To present the clinical and molecular features of a fetus with
      confined trisomy 16 mosaicism with maternal uniparental disomy (UPD), using
      various prenatal diagnostic techniques. MATERIALS AND METHODS: Chromosomal
      karyotyping was performed on samples of chorionic villi, amniotic fluid cells,
      amniotic membrane, umbilical cord, fetal skin, and placenta from a fetus with
      elevated nuchal translucency. Polymorphic short tandem repeat markers and
      Affymetrix single nucleotide polymorphism (SNP) mapping chips were used for
      molecular analyses. RESULTS: Karyotypes from chorionic villi and amniocytes
      showed 47,XX,+16 and 46,XX, respectively. Short tandem repeat markers on
      chromosome 16 suggested maternal UPD for chromosome 16. Affymetrix 10K SNP
      mapping chips were used to simultaneously confirm the difference in karyotypes
      between the placenta and amniocytes and to diagnose UPD for chromosome 16. Fetal
      ultrasonography and magnetic resonance imaging identified severe intrauterine
      growth restriction (IUGR). Autopsy revealed IUGR, incomplete lobulation of
      bilateral lungs, and malrotation of the intestines. The karyotypes of umbilical
      cord, fetal skin and amniotic membrane were 46,XX, and the trisomy 16 karyotype
      appeared to be confined to the placenta. CONCLUSION: UPD should be investigated
      as a possible etiology in all cases of unexplained IUGR. SNP microarrays can be
      useful for confirming this diagnosis.

PMID- 19574179
TI  - Cardiac tamponade: an alternative procedure for late feticide.
AB  - OBJECTIVE: Improvements in equipment and diagnostic skills mean that more
      abnormalities can now be detected antenatally, thus increasing the demand for
      pregnancy termination at later stages of gestation. Potassium chloride injected
      into the fetal circulation is the most frequently used procedure. In this study,
      we propose a new method of feticide using injection of normal saline into the
      fetal pericardial space to induce cardiac tamponade, resulting in late fetal
      reduction with minimal maternal risk. CASE REPORT: A 32-year-old, gravida 6,
      woman was a carrier of a balanced translocation 45,XX,der(2),t(2,22), and had a
      poor obstetric history. Chorionic villus sampling was performed, and the results
      revealed the fetus to be a balanced translocation carrier, like the mother.
      Microcephaly was detected during the third trimester and amniocentesis was
      performed. The results showed a 45,XX,der(2)t(2;22)(q37,q11.2)mat,-22 karyotype.
      After counseling, the mother elected to undergo pregnancy termination. Feticide
      was performed before labor induction. However, she experienced discomfort when a
      minimal amount of potassium chloride (3 mEq) was injected into the fetal heart,
      without inducing fetal asystole. We, therefore, induced cardiac tamponade using
      10 mL of normal saline instilled into the fetal pericardial space. Fetal asystole
      was noted. The whole procedure was performed without incident, and termination
      was achieved by hysterotomy after informed consent was given. CONCLUSION: Many
      methods of feticide have been used, including injection of potassium chloride,
      lidocaine, digoxin or hyperosmolar urea into the fetal circulation. However,
      these methods all use medications or compounds with some potential for maternal
      toxicity or side effects. We provide a relatively safe and effective method of
      feticide for use in late termination of pregnancy.

PMID- 19574180
TI  - Ultrasonographic diagnosis of diastematomyelia during the 14th week of gestation.
AB  - OBJECTIVE: We present a case of type I diastematomyelia diagnosed with
      ultrasonography at the 14th week of gestation. CASE REPORT: A 26-year-old
      primigravida at 14 weeks' gestation was presented to our outpatient department
      with a complaint of dysuria. Routine antenatal ultrasound revealed disruption of
      the fetal upper thoracic vertebral column curvature, together with hemivertebrae.
      Further high-resolution two-dimensional ultrasound examination revealed
      dilatation of the thoracolumbar vertebrae and extra echogenic foci in the spinal
      canal. Thoracolumbar meningocele was also observed. These observations (thoracic
      hemivertebrae, scoliosis and thoracolumbar meningocele) suggested a diagnosis of
      type I diastematomyelia. The family was counseled regarding the prognosis for the
      fetus. Their decision to terminate the pregnancy was considered and approved by
      the ethical council. The postabortion pathologic examination, along with X-ray,
      three-dimensional computed tomography and magnetic resonance imaging
      examinations, supported the initial diagnosis. CONCLUSION: Prenatal diagnosis of
      diastematomyelia during the 14th week of pregnancy is possible using high
      resolution ultrasound. To the best of our knowledge, this is the earliest case
      presented in the literature.

PMID- 19574181
TI  - Metastatic bilateral malignant ovarian tumors associated with pregnancy.
AB  - OBJECTIVE: Krukenberg tumors in pregnancy are extremely rare. Only three cases
      have been reported, two of which were diagnosed postpartum. CASE REPORT: A 20
      year-old, primigravida with bilateral malignant ovarian tumors, who received no
      prior antenatal care, was presented with intestinal obstruction at 5 months'
      gestation. Pregnancy was preserved, and bilateral oophorectomy, omentectomy with
      resection of sigmoid colon growth, and colostomy were performed. The patient
      aborted spontaneously and postoperatively, and was treated with adjuvant
      chemotherapy. CONCLUSION: Because platinum-based chemotherapy can be safely given
      during pregnancy, hysterectomy can be avoided in cases of bilateral malignant
      ovarian tumors if the uterus is not grossly involved, so allowing preservation of
      an existing pregnancy.

PMID- 19574182
TI  - Primary malignant melanoma of the female genital tract.
AB  - OBJECTIVE: Malignant melanoma, which has a highly malignant potential, is a tumor
      of the skin and mucosal membranes. Malignant melanomas of the female genital
      tract, including the vulva and vagina, are rare. Their overall prognosis is poor
      and is worse than that for cutaneous melanomas. CASE REPORTS: Clinical data for
      five patients with primary malignant melanoma are presented. Diagnosis was based
      on histologic and immunohistochemical examinations. Case 1 was a 58-year-old
      woman with mucosal lentiginous melanoma of the vulva. The other four patients,
      all of whom were over 40 years old, had vaginal melanomas. They were all treated
      with surgery, and three also received postoperative adjuvant therapy with
      interferon alpha-2b. Despite this, three of the patients died owing to widespread
      disease. CONCLUSION: Although malignant melanoma of the female genital tract is
      uncommon, elderly women should undergo regular gynecologic examinations and
      suspicious pigmented lesions should be biopsied. The use of immunohistochemical
      assays could markedly improve diagnosis. However, the prognosis for these tumors
      is poor, regardless of the treatment delivered, and they are associated with a
      high rate of recurrence and low long-term survival. Surgery is the best available
      treatment for controlling and potentially curing malignant melanomas.

PMID- 19574184
TI  - Dermatomyositis as the initial presentation of ovarian cancer.

PMID- 19574183
TI  - Retroperitoneal schwannoma mimicking uterine myoma.
AB  - OBJECTIVE: Schwannomas rarely present as pelvic masses. Most of them have been
      previously examined in the pelvis, vagina, retroperitoneum, and mediastinum. We
      report a 44-year-old woman with a pelvic mass initially diagnosed as a uterine
      fibroid but subsequently proven to be a retroperitoneal cellular schwannoma. CASE
      REPORT: Histologic examination revealed the mass to be an Antoni A-dominated
      tumor that was S-100-positive, CD117-negative, and smooth muscle actin-negative.
      The patient underwent a total hysterectomy and removal of the tumor, and had no
      evidence of recurrence at 2 years' follow-up. CONCLUSION: In this case, the
      treatment of choice was complete excision of the tumor, which was considered to
      be curative.

PMID- 19574185
TI  - Acute myocardial infarction during pregnancy.

PMID- 19574186
TI  - Growing teratoma syndrome: an Asian woman with immature teratoma of left ovary
      after chemotherapy.

PMID- 19574187
TI  - Rupture of the renal pelvis following hydronephrosis and hydroureter after a
      cesarean section.

PMID- 19574188
TI  - Heterotopic ovarian pregnancy.

PMID- 19574189
TI  - Transvaginal evisceration in a case with iatrogenic Cushing's syndrome and no
      previous gynecologic surgery.

PMID- 19574190
TI  - Puerperal pelvic hematoma successfully treated by primary transcatheter arterial
      embolization.

PMID- 19574191
TI  - Comment on a cerclage method for hymenoplasty.

PMID- 19574192
TI  - Skin diseases in Europe. Wound healing.

PMID- 19574193
TI  - Skin diseases in Europe. Prevention and rehabilitation.

PMID- 19574194
TI  - Skin diseases in Europe. Dermatooncology.

PMID- 19574195
TI  - Skin diseases in Europe. Dermatological surgery.

PMID- 19574196
TI  - Spanish researchers at the forefront of clinical investigation: the case of
      quality of life in prostate cancer.

PMID- 19574197
TI  - On the road to sadness.

PMID- 19574198
TI  - Why cerebellar glioblastoma is rare and how that indicates adjunctive use of the
      FDA-approved anti-emetic aprepitant might retard cerebral glioblastoma growth: a
      new hypothesis to an old question.

PMID- 19574199
TI  - Wnt signalling and cancer stem cells.
AB  - Intracellular signalling mediated by secreted Wnt proteins is essential for the
      establishment of cell fates and proper tissue patterning during embryo
      development and for the regulation of tissue homeostasis and stem cell function
      in adult tissues. Aberrant activation of Wnt signalling pathways has been
      directly linked to the genesis of different tumours. Here, the components and
      molecular mechanisms implicated in the transduction of Wnt signal, along with
      important results supporting a central role for this signalling pathway in stem
      cell function regulation and carcinogenesis will be briefl y reviewed.

PMID- 19574200
TI  - Clinical-molecular factors predicting response and survival for tyrosine-kinase
      inhibitors.
AB  - The development of drugs with special mechanisms of action, such as tyrosine
      kinase inhibitors (TKIs), means that new clinical-molecular questions are being
      examined and this will help us to better select from the treatments available. In
      this study we review questions of survival and response to TKIs, attempting to
      distinguish prediction-and prognosis-related factors, at both the clinical and
      molecular levels. The evidence available today allows us to affirm that the
      benefits of TKI treatment occur regardless of the patient's status as a smoker,
      his/her gender or histological sub-type. Interestingly, in a subset analysis of
      ever-smokers, men with squamous cell histology derived a statistically
      significant survival benefit from erlotinib, a population that was previously
      thought not to benefit. The question of who should receive TKIs is still not
      completely resolved. Therefore, there should be an international effort to
      achieve a prognostic index, as has been done for lymphomas, that combines
      molecular and clinical factors. Such an index would classify patients into
      several sub-groups, defining the likelihood of non-response to TKIs.

PMID- 19574201
TI  - Hypofractionated radiotherapy for localised prostate cancer. Review of clinical
      trials.
AB  - Over the last 10 years the radiobiology of prostate cancer has been studied both
      in experimental research and in clinical trials of hypofractionated radiotherapy.
      Unlike most cancers, the alpha/beta ratio of the prostatic carcinoma is probably
      lower than that of the healthy organs around the gland, although there is no
      agreement as to how low this alpha/beta really is. This peculiarity implies that,
      theoretically, a hypofractionated schedule would increase the therapeutic gain of
      radiotherapy. Until now, following four published randomised trials,
      hypofractionated radiotherapy has shown results in terms of acute and chronic
      toxicity and tumour control similar to those obtained with conventionally
      fractionated radiotherapy. However, these studies are not conclusive. The two
      studies that involved significant followup used 2D technique and delivered low
      total equivalent dose. On the other hand, the two most recent trials, which
      administered total equivalent doses = or >78 Gy with modern techniques (IMRT,
      IGRT), involved the disadvantage of small samples and a short follow-up period.
      The results of ongoing randomised trials are necessary to confirm the advantages
      of hypofractionation over normofractionated radiotherapy. The impact of
      hypofractionated radiotherapy on the patient's health-related quality of life,
      and on transports and health care costs, should also be investigated.

PMID- 19574202
TI  - Spanish Society of Medical Oncology consensus for the use of haematopoietic
      colony-stimulating factors in cancer patients.
AB  - Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating
      factors (CSF) may be used to avoid neutropenia-associated complications. The
      Spanish Society of Medical Oncology (SEOM) recently constituted a working group
      to review the main issues concerning the use of CSF and carried out a consensus
      process about the use of CSF in cancer patients, held in Madrid on 26 May 2006.
      The group concluded the following recommendations: prophylactic use of CSF is
      recommended when a rate of febrile neutropenia (FN) higher than 20% is expected
      without the use of CSF or when additional risk factors for neutropenia exist;
      therapeutic use of CSF is recommended in order to treat FN episodes but not to
      treat afebrile neutropenic episodes. In addition, the use of CSF is considered
      effective when used to mobilise stem cells before high-dose chemotherapy and when
      used for chemotherapy schedule optimisation in dose-dense and in dose-intense
      regimens.

PMID- 19574203
TI  - mTOR inhibitors and the anti-diabetic biguanide metformin: new insights into the
      molecular management of breast cancer resistance to the HER2 tyrosine kinase
      inhibitor lapatinib (Tykerb).
AB  - The small molecule HER2 tyrosine kinase inhibitor (TKI) lapatinib (Tykerb) is
      approved for the therapy of patients with HER2-positive breast carcinomas who
      have progressed on trastuzumab (Herceptin). Unfortunately, the efficacy of this
      HER2 TKI is limited by both primary (inherent) and acquired resistance, the
      latter typically occurring within 12 months of starting therapy. One of the key
      factors limiting our understanding of the mechanisms involved in lapatinib
      resistance is the lack of published preclinical models. We herein review
      lapatinib-refractory models recently developed at the bench and the survival
      pathways discovered. As hyperactivation of the pharmacologically targetable
      PI3K/mTOR/p70S6K1 axis appears to be central to the occurrence of lapatinib
      resistance, preclinical data showing enhanced antitumour effects when combining
      lapatinib with mTOR inhibitors (e.g., rapamycin analogues and NVP-BEZ235)
      highlight the importance of translational work to yield clinically useful
      regimens capable of delaying or treating lapatinib resistance. The unexpected
      ability of the anti-type II diabetes drug metformin to inactivate mTOR and
      decrease p70S6K1 activity further reveals that this biguanide, generally
      considered non-toxic and remarkably inexpensive, might be considered for new
      combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer
      patients.

PMID- 19574204
TI  - Initial surgical experience in laparoscopic total mesorectal excision for middle
      and lower third rectal cancer: short-term results.
AB  - INTRODUCTION: Total mesorectal excision (TME) of the rectum has been advocated as
      the gold standard surgical treatment of middle and lower third rectal cancer.
      Laparoscopy has gained acceptance among surgeons in the treatment of colon
      malignancies, while scepticism exists about laparoscopic TME in terms of safety
      and its oncological adequacy. OBJECTIVE: To evaluate the impact of laparoscopic
      TME on surgical and oncological outcome in a group of consecutive unselected
      patients. METHODS: One hundred and thirty-two patients with middle or inferior
      rectal cancer were admitted to our unit and underwent TME from December 1998 to
      February 2008. Eighty-nine patients were approached with laparoscopy. Patients
      staged cT3/4 cTxN+ or uTxN+ were submitted to neoadjuvant treatment.
      Postoperative complications and oncological outcomes were registered. RESULTS: In
      the laparoscopic group 80 anterior resections (including 4 intersphincteric
      resections and manual colo- anal anastomosis) and 9 abdominal-perineal resections
      were performed. 33.3% of patients were enrolled in "long-course" neoadjuvant
      chemo-radiotherapy (partial and complete response rates 88.2% and 11.8%,
      respectively). Protective lateral ileostomy was performed in 72% of patients.
      Mean operative time was 254.3+/-38.3 min and mean blood loss was 215+/-180 ml.
      Conversion rate was 12.7%. Morbidity rate was 39.3% without mortality. The rate
      of anastomotic leaks was 13.48%, reoperation rate 13.48%, recovery rate 3.1+/-1.4
      days and hospital stay 10.4+/-4.6 days. Concerning adequacy of oncologic
      resection, mean distance of the tumour from the anal verge was 4.3+/-2.2 cm.
      Nodal sampling of 12.4+/-4.8 were obtained. Six patients (6/89, 6.74%) had a R1
      margin: 3 distal and 3 circumferential. Median follow-up was 29 months and local
      recurrence rate was 5.79%. Four-year cumulative overall survival was 78% and
      disease-free survival was 63% (Kaplan-Meier method). CONCLUSIONS: Laparoscopic
      approach for rectal tumour is a technically demanding procedure, but it is
      oncologically safe.

PMID- 19574205
TI  - Value of the identification of microsatellite instability in colorectal cancer.
AB  - OBJECTIVE: Recent studies defend a possible prognostic and therapeutic value of
      the identification of microsatellite instability (MSI) in colorectal cancer. This
      work tries to assess the impact that the identification of MSI tumours can have
      in clinical practice. MATERIAL AND METHODS: We recovered tumour samples from 92
      of the 143 patients operated on for colorectal cancer in our institution between
      1995 and 2000. Five MSI markers (BAT 25, BAT 26, D2S123, D5S346 and D17S250) were
      studied on them. The rate and clinicopathologic characteristics of MSI tumours
      were investigated along with their impact on the global and disease-free survival
      as compared with microsatellite stable (MSS) tumours. RESULTS: All 5
      microsatellite markers' status were established in 73 patients (79.3% of the
      samples). Among them, 7 tumours showed instability in just one marker (low
      microsatellite instability [MSI-L]) whereas 5 tumours had mutations in 2 or more
      markers (high microsatellite instability [MSI-H]), for a total 15.4% rate of MSI
      tumours. All MSI-H tumours were located in the right colon. We could not fi nd
      any impact from MSI detection on global or disease-free survival. CONCLUSIONS:
      MSI determination did not identify groups of patients with a different prognosis.
      Moreover, with such low incidence its determination can only be justified in
      those cases that fulfill Bethesda's criteria to identify families with Lynch's
      syndrome.

PMID- 19574206
TI  - Quality of life two years after radical prostatectomy, prostate brachytherapy or
      external beam radiotherapy for clinically localised prostate cancer: the Catalan
      Institute of Oncology/Bellvitge Hospital experience.
AB  - OBJECTIVE: The objective was to compare the short- and long-term impact of 3
      different treatment modalities on health-related quality of life (HRQOL) in
      patients treated for localised prostate cancer at a single centre in Catalonia,
      Spain. MATERIAL AND METHODS: This was a longitudinal, prospective study of 304
      patients from a single centre in Catalonia, Spain. Patients underwent 1 of 3
      treatment procedures: radical prostatectomy (114 patients), external beam
      radiation (134) or interstitial brachytherapy (56). HRQOL was assessed by both
      general and specific questionnaires, including the SF-36 health survey and the
      Expanded Prostate Cancer Index Composite (EPIC). Interviews were administered
      prior to treatment and at months 1, 3, 6, 12 and 24. One-way analysis of variance
      and generalised estimating equations models were constructed to assess between
      group differences in HRQOL. RESULTS: After initial deterioration, HRQOL scores
      partially recovered, although significant differences between treatment groups
      persisted at two years. Worsening of urinary incontinence was especially marked
      for the radical prostatectomy group (11.45, p=0.005), while deterioration in the
      urinary irritative/obstructive domain was worse following brachytherapy treatment
      (4.76, p=0.025). Decline in sexual function was significantly greater for the
      radical prostatectomy group than for the brachytherapy group (18.74, p<0.001). No
      significant between-group differences were observed in bowel domain scores.
      CONCLUSIONS: Quality of life 2 years after treatment for prostate cancer shows
      wide variability. Radical prostatectomy had the largest negative impact on the
      sexual and urinary incontinence domains. Differences between external radiation
      and brachytherapy were relatively small. Brachytherapy led to a moderate increase
      in urinary irritation compared to the other 2 groups.

PMID- 19574207
TI  - Pre-treatment serum lactate dehydrogenase level is an important prognostic factor
      in high-grade extremity osteosarcoma.
AB  - BACKGROUND: Treatment of high-grade osteosarcoma remains a challenge. The
      prognostic significance of the pre-treatment serum lactate dehydrogenase (LDH)
      level is currently controversial. PATIENTS AND METHODS: We reviewed records from
      all patients diagnosed with conventional high-grade osteosarcoma at our
      institution over a 25-year period and analysed the prognostic significance of LDH
      in high-grade localised extremity osteosarcomas treated with chemotherapy.
      RESULTS: Between June 1977 and March 2003, 66 patients for whom follow-up was
      available were diagnosed with localised high-grade extremity osteosarcoma and
      treated with chemotherapy. The median age was 15 years, with only 3% older than
      40 years, and the median follow-up was 100 months. The median progression-free
      survival (PFS) was 67 months and the median overall survival (OS) was 113 months.
      The absence of a response to chemotherapy was correlated with a trend toward
      lower PFS and OS. High serum pre-treatment LDH level was associated in
      multivariate analyses with a poorer prognosis for both PFS (HR=8.623, 95%CI: 1.71
      43.37; p=0.009) and for OS (HR=9.38; 95%CI: 1.73-50.74; p=0.009). CONCLUSION: In
      this series, the pre-treatment serum LDH level had an independent prognostic
      value for both PFS and OS in patients with high-grade localised extremity
      osteosarcoma. This measurement should be included in a large prospective
      prognostic series.

PMID- 19574208
TI  - Mantle cell lymphoma stage IV affecting lacrimal glands, retro-orbital tissue,
      optic nerve and ocular motor muscles.
AB  - Mantle cell lymphoma (MCL) is an entity which exceptionally affects the ocular
      region and periorbital tissues, but which should be included in the differential
      diagnosis of lesions which affect the orbital region in a diffused manner. We
      report the case of a 60-year-old patient diagnosed with stage IV MCL, whose fi
      rst clinical manifestation was a result of the damage of lacrimal glands, retro
      orbital tissue and ocular motor muscles. The patient was treated with rituximab
      and chemotherapy, achieving a complete response of those lesions.

PMID- 19574209
TI  - Intertrigo-like eruption caused by pegylated liposomal doxorubicin (PLD).
AB  - Pegylated liposomal doxorubicin (PLD) is a drug whose use is increasingly common.
      It has been associated with a lower rate of haematologic and cardiac side effects
      than its nonencapsulated form. However, mucocutaneous toxicity is quite frequent
      and can be severe. Here we provide a case report of a patient who developed an
      intertrigolike eruption during treatment with PLD.

PMID- 19574210
TI  - Characterization and inhibition of a class II diterpene cyclase from
      Mycobacterium tuberculosis: implications for tuberculosis.
AB  - Mycobacterium tuberculosis remains a widespread and devastating human pathogen,
      whose ability to infiltrate macrophage host cells from the human immune system is
      an active area of investigation. We have recently reported the discovery of a
      novel diterpene from M. tuberculosis, edaxadiene, whose ability to arrest
      phagosomal maturation in isolation presumably contributes to this critical
      process in M. tuberculosis infections. (Mann, F. M., Xu, M., Chen, X., Fulton, D.
      B., Russell, D. G., and Peters, R. J. (2009) J. Am. Chem. Soc., in press). Here,
      we present characterization of the class II diterpene cyclase that catalyzes the
      committed step in edaxadiene biosynthesis, i.e. the previously identified
      halimadienyl-diphosphate synthase (HPS; EC 5.5.1.16). Intriguingly, our kinetic
      analysis suggests a potential biochemical regulatory mechanism that triggers
      edaxadiene production upon phagosomal engulfment. Furthermore, we report
      characterization of potential HPS inhibitors: specifically, two related
      transition state analogs (15-aza-14,15-dihydrogeranylgeranyl diphosphate (7a) and
      15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate (7b)) that exhibit very
      tight binding. Although arguably not suitable for clinical use, these
      nevertheless provide a basis for pharmaceutical design against this intriguing
      biosynthetic pathway. Finally, we provide evidence indicating that this pathway
      exists only in M. tuberculosis and is not functional in the closely related
      Mycobacterium bovis because of an inactivating frameshift in the HPS-encoding
      gene. Thus, we hypothesize that the inability to produce edaxadiene may be a
      contributing factor in the decreased infectivity and/or virulence of M. bovis
      relative to M. tuberculosis in humans.

PMID- 19574211
TI  - The Caenorhabditis elegans A beta 1-42 model of Alzheimer disease predominantly
      expresses A beta 3-42.
AB  - Transgenic expression of human amyloid beta (A beta) peptide in body wall muscle
      cells of Caenorhabditis elegans has been used to better understand aspects of
      Alzheimer disease (AD). In human aging and AD, A beta undergoes post
      translational changes including covalent modifications, truncations, and
      oligomerization. Amino truncated A beta is increasingly recognized as potentially
      contributing to AD pathogenesis. Here we describe surface-enhanced laser
      desorption ionization-time of flight mass spectrometry mass spectrometry of A
      beta peptide in established transgenic C. elegans lines. Surprisingly, the A beta
      being expressed is not full-length 1-42 (amino acids) as expected but rather a 3
      42 truncation product. In vitro analysis demonstrates that A beta(3-42) self
      aggregates like A beta(1-42), but more rapidly, and forms fibrillar structures.
      Similarly, A beta(3-42) is also the more potent initiator of A beta(1-40)
      aggregation. Seeded aggregation via A beta(3-42) is further enhanced via co
      incubation with the transition metal Cu(II). Although unexpected, the C. elegans
      model of A beta expression can now be co-opted to study the proteotoxic effects
      and processing of A beta(3-42).

PMID- 19574212
TI  - Increased protein stability of FGF1 can compensate for its reduced affinity for
      heparin.
AB  - Human FGF1 (fibroblast growth factor 1) is a powerful signaling molecule with a
      short half-life in vivo and a denaturation temperature close to physiological.
      Binding to heparin increases the stability of FGF1 and is believed to be
      important in the formation of FGF1.fibroblast growth factor receptor (FGFR)
      active complex. In order to reveal the function of heparin in FGF1.FGFR complex
      formation and signaling, we constructed several FGF1 variants with reduced
      affinity for heparin and with diverse stability. We determined their biophysical
      properties and biological activities as well as their ability to translocate
      across cellular membranes. Our study showed that increased thermodynamic
      stability of FGF1 nicely compensates for decreased binding of heparin in FGFR
      activation, induction of DNA synthesis, and cell proliferation. By stepwise
      introduction of stabilizing mutations into the K118E (K132E) FGF1 variant that
      shows reduced affinity for heparin and is inactive in stimulation of DNA
      synthesis, we were able to restore the full mitogenic activity of this mutant.
      Our results indicate that the main role of heparin in FGF-induced signaling is to
      protect this naturally unstable protein against heat and/or proteolytic
      degradation and that heparin is not essential for a direct FGF1-FGFR interaction
      and receptor activation.

PMID- 19574213
TI  - Evolutionary basis of converting a bacterial tRNA synthetase into a yeast
      cytoplasmic or mitochondrial enzyme.
AB  - Previous studies showed that cytoplasmic and mitochondrial forms of yeast valyl
      tRNA synthetase (ValRS) are specified by the VAS1 gene through alternative
      initiation of translation. Sequence comparison suggests that the yeast
      cytoplasmic (or mature mitochondrial) ValRS contains an N-terminal appendage that
      acts in cis as a nonspecific tRNA-binding domain (TRBD) and is absent from its
      bacterial relatives. We show here that Escherichia coli ValRS can substitute for
      the mitochondrial and cytoplasmic functions of VAS1 by fusion of a mitochondrial
      targeting signal and a TRBD, respectively. In addition, the bacterial ValRS gene
      can be converted into a dual functional yeast gene encoding both cytoplasmic and
      mitochondrial activities by fusion of a DNA sequence specifying both the
      mitochondrial targeting signal and TRBD. In vitro assays suggested that fusion of
      a nonspecific TRBD to the bacterial enzyme significantly enhanced its yeast tRNA
      binding and aminoacylation activities. These results not only underscore the
      necessity of retaining a TRBD for functioning of a tRNA synthetase in yeast
      cytoplasm, but also provide insights into the evolution of tRNA synthetase genes.

PMID- 19574214
TI  - Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in the
      food vacuole and cytosol.
AB  - The metalloenzyme aminopeptidase P catalyzes the hydrolysis of amino acids from
      the amino termini of peptides with a prolyl residue in the second position. The
      human malaria parasite Plasmodium falciparum expresses a homolog of
      aminopeptidase P during its asexual intraerythrocytic cycle. P. falciparum
      aminopeptidase P (PfAPP) shares with mammalian cytosolic aminopeptidase P a three
      domain, homodimeric organization and is most active with Mn(II) as the cofactor.
      A distinguishing feature of PfAPP is a 120-amino acid amino-terminal extension
      that appears to be removed from the mature protein. PfAPP is present in the food
      vacuole and cytosol of the parasite, a distribution that suggests roles in
      vacuolar hemoglobin catabolism and cytosolic peptide turnover. To evaluate the
      plausibility of these putative functions, the stability and kinetic properties of
      recombinant PfAPP were evaluated at the acidic pH of the food vacuole and at the
      near-neutral pH of the cytosol. PfAPP exhibited high stability at 37 degrees C in
      the pH range 5.0-7.5. In contrast, recombinant human cytosolic APP1 was unstable
      and formed a high molecular weight aggregate at acidic pH. At both acidic and
      slightly basic pH values, PfAPP efficiently hydrolyzed the amino-terminal X-Pro
      bond of the nonapeptide bradykinin and of two globin pentapeptides that are
      potential in vivo substrates. These results provide support for roles for PfAPP
      in peptide catabolism in both the food vacuole and the cytosol and suggest that
      PfAPP has evolved a dual distribution in response to the metabolic needs of the
      intraerythrocytic parasite.

PMID- 19574215
TI  - Aryl-alcohol oxidase involved in lignin degradation: a mechanistic study based on
      steady and pre-steady state kinetics and primary and solvent isotope effects with
      two alcohol substrates.
AB  - Aryl-alcohol oxidase (AAO) is a FAD-containing enzyme in the GMC (glucose
      methanol-choline oxidase) family of oxidoreductases. AAO participates in fungal
      degradation of lignin, a process of high ecological and biotechnological
      relevance, by providing the hydrogen peroxide required by ligninolytic
      peroxidases. In the Pleurotus species, this peroxide is generated in the redox
      cycling of p-anisaldehyde, an extracellular fungal metabolite. In addition to p
      anisyl alcohol, the enzyme also oxidizes other polyunsaturated primary alcohols.
      Its reaction mechanism was investigated here using p-anisyl alcohol and 2,4
      hexadien-1-ol as two AAO model substrates. Steady state kinetic parameters and
      enzyme-monitored turnover were consistent with a sequential mechanism in which
      O(2) reacts with reduced AAO before release of the aldehyde product. Pre-steady
      state analysis revealed that the AAO reductive half-reaction is essentially
      irreversible and rate limiting during catalysis. Substrate and solvent kinetic
      isotope effects under steady and pre-steady state conditions (the latter showing
      approximately 9-fold slower enzyme reduction when alpha-bideuterated substrates
      were used, and approximately 13-fold slower reduction when both substrate and
      solvent effects were simultaneously evaluated) revealed a synchronous mechanism
      in which hydride transfer from substrate alpha-carbon to FAD and proton
      abstraction from hydroxyl occur simultaneously. This significantly differs from
      the general mechanism proposed for other members of the GMC oxidoreductase family
      that implies hydride transfer from a previously stabilized substrate alkoxide.

PMID- 19574216
TI  - Thiolation controls cytoplasmic tRNA stability and acts as a negative determinant
      for tRNA editing in mitochondria.
AB  - Kinetoplastids encode a single nuclear tryptophanyl tRNA that contains a CCA
      anticodon able to decode the UGG codons used in cytoplasmic protein synthesis but
      cannot decode the mitochondrial UGA codons. Following mitochondrial import, this
      problem is circumvented in Trypanosoma brucei by specifically editing the
      tRNA(Trp) anticodon to UCA, which can now decode the predominant mitochondrial
      UGA tryptophan codons. This tRNA also undergoes an unusual thiolation at position
      33 of the anticodon loop, the only known modification at U33 in any tRNA. In
      other organisms, tRNA thiolation is mediated by the cysteine desulfurase, Nfs1
      (IscS). However, T. brucei encodes two Nfs homologues, one cytoplasmic and the
      other mitochondrial. We show by a combination of RNA interference and Northern
      and Western analyses that the mitochondria-targeted TbNfs, and not TbNfs-like
      protein, is essential for thiolation of both cytosolic and mitochondrial tRNAs.
      Given the exclusive mitochondrial localization of TbNfs, how it mediates
      thiolation in the cytoplasm remains unclear. Furthermore, thiolation specifically
      affects thiolated tRNA stability in the cytoplasm but more surprisingly acts as a
      negative determinant for the essential C to U editing in T. brucei. This provides
      a first line of evidence for mitochondrial C to U editing regulation in this
      system.

PMID- 19574217
TI  - An adenylyl cyclase-mAKAPbeta signaling complex regulates cAMP levels in cardiac
      myocytes.
AB  - Protein kinase A-anchoring proteins (AKAPs) play important roles in the
      compartmentation of cAMP signaling, anchoring protein kinase A (PKA) to specific
      cellular organelles and serving as scaffolds that assemble localized signaling
      cascades. Although AKAPs have been recently shown to bind adenylyl cyclase (AC),
      the functional significance of this association has not been studied. In cardiac
      myocytes, the muscle protein kinase A-anchoring protein beta (mAKAPbeta)
      coordinates cAMP-dependent, calcium, and MAP kinase pathways and is important for
      cellular hypertrophy. We now show that mAKAPbeta selectively binds type 5 AC in
      the heart and that mAKAPbeta-associated AC activity is absent in AC5 knock-out
      hearts. Consistent with its known inhibition by PKA phosphorylation, AC5 is
      inhibited by association with mAKAPbeta-PKA complexes. AC5 binds to a unique N
      terminal site on mAKAP-(245-340), and expression of this peptide disrupts
      endogenous mAKAPbeta-AC association. Accordingly, disruption of mAKAPbeta-AC5
      complexes in neonatal cardiac myocytes results in increased cAMP and hypertrophy
      in the absence of agonist stimulation. Taken together, these results show that
      the association of AC5 with the mAKAPbeta complex is required for the regulation
      of cAMP second messenger controlling cardiac myocyte hypertrophy.

PMID- 19574218
TI  - Dissecting activation of the PAK1 kinase at protrusions in living cells.
AB  - The p21-activated kinase (PAK) 1 kinase, an effector of the Cdc42 and Rac1
      GTPases, regulates cell protrusions and motility by controlling actin and
      adhesion dynamics. Its deregulation has been linked to human cancer. We show here
      that activation of PAK1 is necessary for protrusive activity during cell
      spreading. To investigate PAK1 activation dynamics at live protrusions, we
      developed a conformational biosensor, based on fluorescence resonance energy
      transfer. This novel PAK1 biosensor allowed the spatiotemporal visualization of
      PAK1 activation during spreading of COS-7 cells and during motility of normal rat
      kidney cells. By using this imaging approach in COS-7 cells, the following new
      insights on PAK1 regulation were unveiled. First, PAK1 acquires an intermediate
      semi-open conformational state upon recruitment to the plasma membrane. This semi
      open PAK1 species is selectively autophosphorylated on serines in the N-terminal
      regulatory region but not on the critical threonine 423 in the catalytic site.
      Second, this intermediate PAK1 state is hypersensitive to stimulation by Cdc42
      and Rac1. Third, interaction with PIX proteins contributes to PAK1 stimulation at
      membrane protrusions, in a GTPase-independent way. Finally, trans-phosphorylation
      events occur between PAK1 molecules at the membrane possibly playing a relevant
      role for its activation. This study leads to a model for the complex and accurate
      regulation of PAK1 kinase in vivo at cell protrusions.

PMID- 19574219
TI  - An in trans interaction at the interface of the helicase and primase domains of
      the hexameric gene 4 protein of bacteriophage T7 modulates their activities.
AB  - DNA helicase and primase are essential for DNA replication. The helicase unwinds
      the DNA to provide single-stranded templates for DNA polymerase. The primase
      catalyzes the synthesis of oligoribonucleotides for the initiation of lagging
      strand synthesis. The two activities reside in a single polypeptide encoded by
      gene 4 of bacteriophage T7. Their coexistence within the same polypeptide
      facilitates their coordination during DNA replication. One surface of helix E
      within the helicase domain is positioned to interact with the primase domain and
      the linker connecting the two domains within the functional hexamer. The
      interaction occurs in trans such that helix E interacts with the primase domain
      and the linker of the adjacent subunit. Most alterations of residues on the
      surface of helix E (Arg(404), Lys(408), Tyr(411), and Gly(415)) eliminate the
      ability of the altered proteins to complement growth of T7 phage lacking gene 4.
      Both Tyr(411) and Gly(415) are important in oligomerization of the protein.
      Alterations G415V and K408A simultaneously influence helicase and primase
      activities in opposite manners that mimic events observed during coordinated DNA
      synthesis. The results suggest that Asp(263) located in the linker of one subunit
      can interact with Tyr(411), Lys(408), or Arg(404) in helix E of the adjacent
      subunit depending on the oligomerization state. Thus the switch in contacts
      between Asp(263) and its three interacting residues in helix E of the adjacent
      subunit results in conformational changes that modulate helicase and primase
      activity.

PMID- 19574220
TI  - Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9.
AB  - Collagen XVII is a transmembrane collagen and the major autoantigen of the
      autoimmune skin blistering disease bullous pemphigoid. Collagen XVII is
      proteolytically released from the membrane, and the pathogenic epitope harbors
      the cleavage site for its ectodomain shedding, suggesting that proteolysis has an
      important role in regulating the function of collagen XVII in skin homeostasis.
      Previous studies identified ADAMs 9, 10, and 17 as candidate collagen XVII
      sheddases and suggested that ADAM17 is a major sheddase. Here we show that ADAM17
      only indirectly affects collagen XVII shedding and that ADAMs 9 and 10 are the
      most prominent collagen XVII sheddases in primary keratinocytes because (a)
      collagen XVII shedding was not stimulated by phorbol esters, known activators of
      ADAM17, (b) constitutive and calcium influx-stimulated shedding was sensitive to
      the ADAM10-selective inhibitor GI254023X and was strongly reduced in Adam10(-/-)
      cells, (c) there was a 55% decrease in constitutive collagen XVII ectodomain
      shedding from Adam9(-/-) keratinocytes, and (d) H(2)O(2) enhanced ADAM9
      expression and stimulated collagen XVII shedding in skin and keratinocytes of
      wild type mice but not of Adam9(-/-) mice. We conclude that ADAM9 and ADAM10 can
      both contribute to collagen XVII shedding in skin with an enhanced relative
      contribution of ADAM9 in the presence of reactive oxygen species. These results
      provide critical new insights into the identity and regulation of the major
      sheddases for collagen XVII in keratinocytes and skin and have implications for
      the treatment of blistering diseases of the skin.

PMID- 19574221
TI  - Transforming growth factor-beta1 (TGF-beta1) induces human osteoclast apoptosis
      by up-regulating Bim.
AB  - Transforming growth factor-beta1 (TGF-beta1) is the most abundant TGF-beta
      isoform detected in bone and is an important functional modulator of osteoclasts.
      TGF-beta1 can induce osteoclast apoptosis; however, the apoptotic pathways
      involved in this process are not known. We show here that human osteoclasts
      express both type-I and type-II TGF-beta receptors. In the absence of survival
      factors, TGF-beta1 (1 ng/ml) induced osteoclast apoptosis. The expression of
      activated caspase-9, but not that of caspase-8, was increased by TGF-beta1
      stimulation, and the rate of TGF-beta1-induced apoptosis was significantly lower
      in the presence of a caspase-9 inhibitor. To study further the mechanisms
      involved in TGF-beta1-induced osteoclast apoptosis, we investigated TGF-beta1
      signaling, which primarily involves the Smad pathway, but also other pathways
      that may interfere with intracellular modulators of apoptosis, such as mitogen
      activated protein (MAP) kinases and Bcl2 family members. We show here that early
      events consisted of a trend toward increased expression of extracellular signal
      regulated kinase (ERK), and then TGF-beta1 significantly induced the activation
      of p38 and Smad2 in a time-dependent manner. These signaling cascades may
      activate the intrinsic apoptosis pathway, which involves Bim, the expression of
      which was increased in the presence of TGF-beta1. Furthermore, the rate of TGF
      beta1-induced osteoclast apoptosis was lower when Bim expression was suppressed,
      and inhibiting the Smad pathway abolished Bim up-regulation following TGF-beta
      stimulation. This could correspond to a regulatory mechanism involved in the
      inhibition of osteoclast activity by TGF-beta1.

PMID- 19574222
TI  - Mutation of a phosphorylatable residue in Put3p affects the magnitude of
      rapamycin-induced PUT1 activation in a Gat1p-dependent manner.
AB  - Saccharomyces cerevisiae can utilize high quality (e.g. glutamine and ammonia) as
      well as low quality (e.g. gamma-amino butyric acid and proline) nitrogen sources.
      The transcriptional activator Put3p allows yeast cells to utilize proline as a
      nitrogen source through expression of the PUT1 and PUT2 genes. Put3p activates
      high level transcription of these genes by binding proline directly. However,
      Put3p also responds to other lower quality nitrogen sources. As nitrogen quality
      decreases, Put3p exhibits an increase in phosphorylation concurrent with an
      increase in PUT gene expression. The proline-independent activation of the PUT
      genes requires both Put3p and the positively acting GATA factors, Gln3p and
      Gat1p. Conversely, the phosphorylation of Put3p is not dependent on GATA factor
      activity. Here, we find that the mutation of Put3p at amino acid Tyr-788
      modulates the proline-independent activation of PUT1 through Gat1p. The
      phosphorylation of Put3p appears to influence the association of Gat1p, but not
      Gln3p, to the PUT1 promoter. Combined, our findings suggest that this may
      represent a mechanism through which yeast cells rapidly adapt to use proline as a
      nitrogen source under nitrogen limiting conditions.

PMID- 19574223
TI  - Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer
      cells.
AB  - The FOXO1 transcription factor orchestrates the regulation of genes involved in
      the apoptotic response, cell cycle checkpoints, and cellular metabolism. FOXO1 is
      a putative tumor suppressor, and the expression of this gene is dysregulated in
      some cancers, including prostate and endometrial cancers. However, the molecular
      mechanism resulting in aberrant expression of human FOXO1 in cancer cells is
      poorly understood. We show here that FOXO1 mRNA is down-regulated in breast tumor
      samples as compared with normal breast tissue. Silencing of the microRNA
      processing enzymes, Drosha and Dicer, led to an increase in FOXO1 expression. We
      also identified functional and specific microRNA target sites in the FOXO1 3'
      untranslated region for miR-27a, miR-96, and miR-182, microRNAs that have
      previously been linked to oncogenic transformation. The three microRNAs, miR-27a,
      miR-96 and miR-182, were observed to be highly expressed in MCF-7 breast cancer
      cells, in which the level of FOXO1 protein is very low. Antisense inhibitors to
      each of these microRNAs led to a significant increase in endogenous FOXO1
      expression and to a decrease in cell number in a manner that was blocked by FOXO1
      siRNA. Overexpression of FOXO1 resulted in decreased cell viability because of
      inhibition of cell cycle traverse and induction of cell death. We have identified
      a novel mechanism of FOXO1 regulation, and targeting of FOXO1 by microRNAs may
      contribute to transformation or maintenance of an oncogenic state in breast
      cancer cells.

PMID- 19574224
TI  - The glycolytic inhibitor 2-deoxyglucose activates multiple prosurvival pathways
      through IGF1R.
AB  - Recent molecular studies indicate that aerobic glycolysis plays an important role
      in tumorigenesis and is a valid target for cancer therapy. Although 2
      deoxyglucose (2-DG) is well characterized as a glycolytic inhibitor, we recently
      discovered that it activates a prosurvival oncoprotein, AKT, through PI3K. In
      this study, we discovered that 2-DG treatments disrupted the binding between
      insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) so that
      the free form of IGF-1 could be released from the IGF-1.IGFBP3 complex to
      activate IGF-1 receptor (IGF1R) signaling. Because IGF1R signaling is involved,
      PI3K/AKT constitutes only one of the prosurvival pathways that are activated by 2
      DG treatment; we validated that MEK-ERK signaling was also induced in an IGF1R
      dependent manner in some cancer cell lines. Furthermore, our phospho-specific
      antibody microarray analysis indicated that 2-DG up-regulated the phosphorylation
      of 64 sites within various signaling pathways in H460 cells. Chemical inhibition
      of IGF1R reduced 57 of these up-regulations. These data suggest that 2-DG-induced
      activation of many survival pathways can be jointly attenuated through IGF1R
      inhibition. Our in vitro analysis demonstrated that treatment with a combination
      of subtoxic doses of 2-DG and the IGF1R inhibitor II reduced cancer cell
      proliferation 90% and promoted significant apoptosis.

PMID- 19574225
TI  - The functional curli amyloid is not based on in-register parallel beta-sheet
      structure.
AB  - The extracellular curli proteins of Enterobacteriaceae form fibrous structures
      that are involved in biofilm formation and adhesion to host cells. These curli
      fibrils are considered a functional amyloid because they are not a consequence of
      misfolding, but they have many of the properties of protein amyloid. We confirm
      that fibrils formed by CsgA and CsgB, the primary curli proteins of Escherichia
      coli, possess many of the hallmarks typical of amyloid. Moreover we demonstrate
      that curli fibrils possess the cross-beta structure that distinguishes protein
      amyloid. However, solid state NMR experiments indicate that curli structure is
      not based on an in-register parallel beta-sheet architecture, which is common to
      many human disease-associated amyloids and the yeast prion amyloids. Solid state
      NMR and electron microscopy data are consistent with a beta-helix-like structure
      but are not sufficient to establish such a structure definitively.

PMID- 19574226
TI  - Gga2 mediates sequential ubiquitin-independent and ubiquitin-dependent steps in
      the trafficking of ARN1 from the trans-Golgi network to the vacuole.
AB  - In Saccharomyces cerevisiae, ARN1 encodes a transporter for the uptake of
      ferrichrome, an important nutritional source of iron. In the absence of
      ferrichrome, Arn1p is sorted directly from the trans-Golgi network (TGN) to the
      vacuolar lumen via the vacuolar protein-sorting pathway. Arn1p is mis-sorted to
      the plasma membrane in cells lacking Gga2p, a monomeric clathrin-adaptor protein
      involved in vesicular transport from the TGN. Although Ggas have been
      characterized as ubiquitin receptors, we show here that ubiquitin binding by Gga2
      was not required for the TGN-to-endosome trafficking of Arn1, but it was required
      for subsequent sorting of Arn1 into the multivesicular body. In a ubiquitin
      binding mutant of Gga2, Arn1p accumulated on the vacuolar membrane in a
      ubiquitinated form. The yeast epsins Ent3p and Ent4p were also involved in TGN-to
      vacuole sorting of Arn1p. Amino-terminal sequences of Arn1p were required for
      vacuolar protein sorting, as mutation of ubiquitinatable lysine residues resulted
      in accumulation on the vacuolar membrane, and mutation of either a THN or YGL
      sequence resulted in mis-sorting to the plasma membrane. These studies suggest
      that Gga2 is involved in sorting at both the TGN and multivesicular body and that
      the first step can occur without ubiquitin binding.

PMID- 19574227
TI  - Drosomycin, an innate immunity peptide of Drosophila melanogaster, interacts with
      the fly voltage-gated sodium channel.
AB  - Several peptide families, including insect antimicrobial peptides, plant protease
      inhibitors, and ion channel gating modifiers, as well as blockers from scorpions,
      bear a common CSalphabeta scaffold. The high structural similarity between two
      peptides containing this scaffold, drosomycin and a truncated scorpion beta
      toxin, has prompted us to examine and compare their biological effects.
      Drosomycin is the most expressed antimicrobial peptide in Drosophila melanogaster
      immune response. A truncated scorpion beta-toxin is capable of binding and
      inducing conformational alteration of voltage-gated sodium channels. Here, we
      show that both peptides (i) exhibit anti-fungal activity at micromolar
      concentrations; (ii) enhance allosterically at nanomolar concentration the
      activity of LqhalphaIT, a scorpion alpha toxin that modulates the inactivation of
      the D. melanogaster voltage-gated sodium channel (DmNa(v)1); and (iii) inhibit
      the facilitating effect of the polyether brevetoxin-2 on DmNa(v)1 activation.
      Thus, the short CSalphabeta scaffold of drosomycin and the truncated scorpion
      toxin can maintain more than one bioactivity, and, in light of this new
      observation, we suggest that the biological role of peptides bearing this
      scaffold should be carefully examined. As for drosomycin, we discuss the
      intriguing possibility that it has additional functions in the fly, as implied by
      its tight interaction with DmNa(v)1.

PMID- 19574228
TI  - Proteolytic processing of HCN2 and co-assembly with HCN4 in the generation of
      cardiac pacemaker channels.
AB  - In sino-atrial and atrio-ventricular nodal cells, hyperpolarization-activated
      cyclic nucleotide-gated (HCN) inward current carrying cationic channels, I(f),
      are expressed that contribute importantly to the diastolic depolarization
      critical for cardiac pacemaker activity. Although previous studies have
      demonstrated myocardial expression of both the HCN2 and HCN4 subunits, the
      specific roles of these subunits in the generation of functional myocardial I(f)
      channels remain unclear. To explore the molecular compositions of functional
      cardiac I(f) channels, antibodies targeted against specific C- and N-terminal
      sequences in HCN2 and HCN4 were exploited to examine HCN2 and HCN4 subunit
      expression in adult (mouse) heart and to immunoprecipitate endogenous HCN-encoded
      cardiac I(f) channel complexes. Western blot experiments revealed that although
      the full-length HCN2 (105 kDa) and HCN4 (160 kDa) proteins are readily detected
      in transiently transfected HEK-293 cells and in adult (mouse) brain, the
      molecular mass of the HCN2 protein in the myocardium is approximately 60 kDa. In
      addition, the myocardial 60-kDa HCN2 protein lacks the C terminus, which contains
      the cAMP binding domain. In heterologous cells, the C-terminal-truncated HCN2
      protein co-assembles with HCN4 to form functional heteromeric HCN channels, which
      activate faster than homomeric HCN2 or homomeric HCN4 channels, and display
      properties similar to endogenous myocardial I(f) channels Taken together, these
      results suggest that functional myocardial I(f) channels reflect the heteromeric
      assembly of HCN2 and HCN4 subunits and further that the HCN4 subunit underlies
      the cAMP-mediated regulation of cardiac I(f) channels.

PMID- 19574229
TI  - Molecular dissection of Erv26p identifies separable cargo binding and coat
      protein sorting activities.
AB  - Efficient export of secretory alkaline phosphatase (ALP) from the endoplasmic
      reticulum depends on the conserved transmembrane sorting adaptor Erv26p/Svp26p.
      In the present study we investigated the mechanism by which Erv26p couples pro
      ALP to the coat protein complex II (COPII) export machinery. Site-specific
      mutations were introduced into Erv26p, and mutant proteins were assessed in cell
      free assays that monitor interactions with pro-ALP cargo and packaging into COPII
      vesicles. Mutations in the second and third loop domains of Erv26p inhibited
      interaction with pro-ALP, whereas mutations in the C-terminal tail sequence
      influenced incorporation into COPII vesicles and subcellular distribution.
      Interestingly mutations in the second loop domain also influenced Erv26p
      homodimer associations. Finally we demonstrated that Ktr3p, a cis-Golgi-localized
      mannosyltransferase, also relies on Erv26p for efficient COPII-dependent export
      from the endoplasmic reticulum. These findings demonstrate that Erv26p acts as a
      protein sorting adaptor for a variety of Type II transmembrane cargo proteins and
      requires domain-specific interactions with both cargo and coat subunits to
      promote efficient secretory protein transport.

PMID- 19574230
TI  - FACT and the proteasome promote promoter chromatin disassembly and
      transcriptional initiation.
AB  - The packaging of the eukaryotic genome into chromatin represses gene expression
      by blocking access of the general transcription machinery to the underlying DNA
      sequences. Accordingly, eukaryotes have developed a variety of mechanisms to
      disrupt, alter, or disassemble nucleosomes from promoter regions and open reading
      frames to allow transcription to occur. Although we know that chromatin
      disassembly from the yeast PHO5 promoter is triggered by the Pho4 activator, the
      mechanism is far from clear. Here we show that the Pho4 activator can occupy its
      nucleosome-bound DNA binding site within the PHO5 promoter. In contrast to the
      role of Saccharomyces cerevisiae FACT (facilitates chromatin transcription)
      complex in assembling chromatin within open reading frames, we find that FACT is
      involved in the disassembly of histones H2A/H2B from the PHO5 promoter during
      transcriptional induction. We have also discovered that the proteasome is
      required for efficient chromatin disassembly and transcriptional induction from
      the PHO5 promoter. Mutants of the degradation function of the proteasome have a
      defect in recruitment of the Pho4 activator, whereas mutants of the ATPase cap of
      the proteasome do recruit Pho4 but are still delayed for chromatin assembly.
      Finally, we rule out the possibility that the proteasome or ATPase cap is driving
      chromatin disassembly via a potential ATP-dependent chromatin remodeling
      activity.

PMID- 19574231
TI  - Isolation and characterization of a high affinity peptide inhibitor of ClC-2
      chloride channels.
AB  - The ClC protein family includes voltage-gated chloride channels and
      chloride/proton exchangers. In eukaryotes, ClC proteins regulate membrane
      potential of excitable cells, contribute to epithelial transport, and aid in
      lysosomal acidification. Although structure/function studies of ClC proteins have
      been aided greatly by the available crystal structures of a bacterial ClC
      chloride/proton exchanger, the availability of useful pharmacological tools, such
      as peptide toxin inhibitors, has lagged far behind that of their cation channel
      counterparts. Here we report the isolation, from Leiurus quinquestriatus hebraeus
      venom, of a peptide toxin inhibitor of the ClC-2 chloride channel. This toxin,
      GaTx2, inhibits ClC-2 channels with a voltage-dependent apparent K(D) of
      approximately 20 pm, making it the highest affinity inhibitor of any chloride
      channel. GaTx2 slows ClC-2 activation by increasing the latency to first opening
      by nearly 8-fold but is unable to inhibit open channels, suggesting that this
      toxin inhibits channel activation gating. Finally, GaTx2 specifically inhibits
      ClC-2 channels, showing no inhibitory effect on a battery of other major classes
      of chloride channels and voltage-gated potassium channels. GaTx2 is the first
      peptide toxin inhibitor of any ClC protein. The high affinity and specificity
      displayed by this toxin will make it a very powerful pharmacological tool to
      probe ClC-2 structure/function.

PMID- 19574233
TI  - Early mortality in systemic vasculitis: relative contribution of adverse events
      and active vasculitis.
AB  - OBJECTIVE: To contrast the effect of the burden of vasculitis activity with the
      burden of adverse events on 1-year mortality of patients with antineutrophil
      cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study assessed
      the outcome and adverse events in patients prospectively recruited to four
      European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were
      included. The burden of adverse events was quantified using a severity score for
      leucopenia, infection and other adverse events, with an additional weighting for
      follow-up duration. A 'combined burden of events' (CBOE) score was generated for
      each patient by summing the individual scores. Vasculitis severity was quantified
      using the Birmingham vasculitis activity score and glomerular filtration rate
      (GFR). RESULTS: 1-year mortality probability was 11.1%; 59% and 14% of deaths
      were caused by therapy-associated adverse events and active vasculitis,
      respectively. Using Cox regression analysis, infection score (p<0.001), adverse
      event score (p<0.001), leucopenia score (p<0.001) and GFR (p=0.002) were
      independently associated with mortality. The risk of 1-year mortality remained
      low (5%) with CBOE scores less than 7, but increased dramatically with scores
      above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI
      8.4 to 24.8). Age and GFR were independent predictors of CBOE score. CONCLUSIONS:
      The greatest threat to patients with AAV in the first year of therapy is from
      adverse events rather than active vasculitis. The accumulation of adverse events,
      monitored using this scoring method, should prompt increased awareness that the
      patient is at high risk of death.

PMID- 19574232
TI  - Identification of specific hemopexin-like domain residues that facilitate matrix
      metalloproteinase collagenolytic activity.
AB  - Collagen serves as a structural scaffold and a barrier between tissues, and thus
      collagen catabolism (collagenolysis) is required to be a tightly regulated
      process in normal physiology. In turn, the destruction or damage of collagen
      during pathological states plays a role in tumor growth and invasion, cartilage
      degradation, or atherosclerotic plaque formation and rupture. Several members of
      the matrix metalloproteinase (MMP) family catalyze the hydrolysis of collagen
      triple helical structure. This study has utilized triple helical peptide (THP)
      substrates and inhibitors to dissect MMP-1 collagenolytic behavior. Analysis of
      MMP-1/THP interactions by hydrogen/deuterium exchange mass spectrometry followed
      by evaluation of wild type and mutant MMP-1 kinetics led to the identification of
      three noncatalytic regions in MMP-1 (residues 285-295, 302-316, and 437-457) and
      two specific residues (Ile-290 and Arg-291) that participate in collagenolysis.
      Ile-290 and Arg-291 contribute to recognition of triple helical structure and
      facilitate both the binding and catalysis of the triple helix. Evidence from this
      study and prior studies indicates that the MMP-1 catalytic and hemopexin-like
      domains collaborate in collagen catabolism by properly aligning the triple helix
      and coupling conformational states to facilitate hydrolysis. This study is the
      first to document the roles of specific residues within the MMP-1 hemopexin-like
      domain in substrate binding and turnover. Noncatalytic sites, such as those
      identified here, can ultimately be utilized to create THP inhibitors that target
      MMPs implicated in disease progression while sparing proteases with host
      beneficial functions.

PMID- 19574234
TI  - The effects of social variables on symptom recognition and medical care seeking
      behaviour for acute respiratory infections in infants in urban Mongolia.
AB  - OBJECTIVE: To investigate potentially modifiable factors associated with carers'
      recognition of symptoms and timely presentation of infants with acute respiratory
      infections (ARI) in urban Mongolia. METHODS: A prospective cohort study nested in
      a randomised controlled trial of infant swaddling. Data were collected on social,
      educational and childcare variables and all doctor contacts for ARI in primary
      and secondary care by regular questionnaires to carers of infants during the
      first 6 months of life. FINDINGS: Analyses were based on 9024 ARI related doctor
      contacts for 4554 illness episodes in 1218 infants. Delay in medical care seeking
      (>3 days from acute lower respiratory infection (ALRI) symptom onset) was
      associated with younger maternal age (OR (95% CI) 3.8 (1.2 to 11.6)), single
      child families (3.8 (1.2 to 11.61)), absent father (4.1 (1.2 to 14.4)) and
      residence more than 1 km from a clinic (3.5 (1.2 to 10.2)). CONCLUSION: There is
      a continuing need to educate carers of infants in the management of ARI,
      particularly those of younger age and those with limited family support.

PMID- 19574235
TI  - Pubertal anthropometry in sons and daughters of women with preeclamptic or
      normotensive pregnancies.
AB  - OBJECTIVE: To compare body mass index (BMI) and waist and hip circumference in
      early puberty (10.8 years in girls and 11.8 years in boys) among offspring of
      preeclamptic and normotensive pregnancies. DESIGN: Population based follow-up
      study. METHODS: Anthropometry measured in early puberty in 91 girls and 92 boys
      of preeclamptic pregnancies, and in 194 girls and 166 boys of normotensive
      pregnancies, with similar anthropometric measures among mothers, performed at the
      beginning of the index pregnancy, and at follow-up, when their offspring were in
      early puberty. RESULTS: Among girls, the preeclampsia group had higher body mass
      (BMI 18.3 kg/m(2) vs 17.5 kg/m(2), p = 0.01) and larger waist circumference (63.7
      cm vs 61.6 cm, p = 0.05) compared to the normotensive group, but the differences
      were restricted to the offspring of mothers with a high body mass (BMI >30
      kg/m(2)). Among boys, we observed no differences in anthropometric measurements
      between groups. CONCLUSIONS: The higher BMI and larger waist of daughters of
      women with preeclampsia was only present if their mothers were obese. These
      results suggest that preeclampsia in obese women may lead to a distinct
      disadvantage in body size for their daughters in early puberty.

PMID- 19574236
TI  - Vestibular PREHAB and gentamicin before schwannoma surgery may improve long-term
      postural function.
AB  - BACKGROUND: Unilateral vestibular deafferentation (uVD), as performed in
      vestibular schwannoma surgery, results in a chronic vestibular deficit, though
      most of the insufficiency can be compensated by other sensory input. By
      vestibular training (prehabituation) performed before surgery, motor adaptation
      processes can be instigated before the actual lesion. The adaptation processes of
      the altered sensory input could be affected if the vestibular ablation and
      surgery were separated in time, by pretreating patients who have remaining
      vestibular function with gentamicin. OBJECTIVE: To determine whether presurgical
      deafferentation would affect postsurgery postural control also in a long-term
      perspective (6 months). METHOD: 41 patients subjected to trans-labyrinthine
      schwannoma surgery were divided into four groups depending on the vestibular
      activity before surgery (with no clinical significant remaining function n = 17;
      with remaining function n = 8), whether signs of central lesions were present (n
      = 10), and if patients with remaining vestibular activity were treated with
      gentamicin with the aim to produce uVD before surgery (n = 6). The vibratory
      posturography recordings before surgery and at the follow-up 6 months after
      surgery were compared. RESULTS: The subjects pretreated with gentamicin had
      significantly less postural sway at the follow-up, both compared with the
      preoperative recordings and compared with the other groups. CONCLUSION: The
      results indicate that by both careful sensory training and separating the
      surgical trauma and the effects of uVD in time, adaptive processes can develop
      more efficiently to resolve sensory conflicts, resulting in a reduction of
      symptoms not only directly after surgery but also perhaps up to 6 months
      afterwards.

PMID- 19574237
TI  - The Wies procedure for management of trichiasis or cicatricial entropion of
      either upper or lower eyelids.
AB  - AIM: To report the efficacy of the Wies procedure (transverse blepharotomy and
      marginal rotation) in the management of trichiasis or cicatricial entropion of
      the upper or lower eyelid. METHODS: A retrospective chart review was performed of
      all cases of Wies eyelid rotations supervised or performed by one surgeon for
      cicatricial entropion or trichiasis of the upper or lower eyelids over a 16-year
      period to assess the indications, success rate and complications of the
      procedure. Where follow-up was less than 6 months, telephone interviews were
      conducted to assess patient satisfaction with the surgery. Patients not meeting
      these criteria were excluded from the final analysis. Success was defined as no
      recurrence of the entropion or trichiasis and/or patient satisfaction at least 6
      months postoperatively. Statistical analysis was performed using a chi(2) test.
      RESULTS: 126 eyelids (77 upper lids, 49 lower lids) were identified in 89
      patients (53 single eyelid, 33 multiple eyelids) who underwent a Wies procedure
      with a minimum follow-up period of 6 months. The mean follow-up period was 67
      months (range 6-188 months). The overall success rate was 85%. 13 eyelids (10%)
      developed complications. 18 eyelids (14%) developed recurrences that required a
      second procedure. 10 of these second procedures were repeat Wies procedures, one
      of which was followed by electrolysis. All of these second Wies procedures were
      successful. CONCLUSIONS: The Wies procedure (transverse blepharotomy and marginal
      rotation) is reasonably successful in managing trichiasis and cicatricial
      entropion of either upper or lower eyelids.

PMID- 19574238
TI  - Comparison of long-term surgical success of Ahmed Valve implant versus
      trabeculectomy in open-angle glaucoma.
AB  - AIM: To compare the long-term intraocular pressure (IOP) outcomes of Ahmed
      Glaucoma Valve (AGV) implantation to trabeculectomy with mitomycin C (MMC) in
      open-angle glaucoma (OAG). METHODS: 78 OAG patients who underwent AGV
      implantation were matched with respect to age, preoperative surgery, preoperative
      IOP and preoperative medicines to 88 OAG patients who underwent trabeculectomy
      with MMC with a minimum of 3 years' follow-up. The cumulative probability of
      success between the two groups with different criteria was analysed: (1) an IOP <
      or =21 mm Hg and a reduction of IOP>/=15% from baseline; and (2) an IOP < or =18
      mm Hg and a reduction of IOP > or =20% from baseline. No loss of light
      perception, no additional glaucoma surgery and no hypotony were also required.
      RESULTS: The 5-year cumulative probability of success was not statistically
      significant between eyes that had an AGV or trabeculectomy with MMC when success
      was defined as criteria A (p = 0.094). However, when success was defined
      according to criteria B, eyes undergoing trabeculectomy with MMC had a higher
      rate of success (p = 0.024). CONCLUSIONS: Trabeculectomy with MMC has a
      significantly higher 5-year cumulative probability of success compared with AGV
      implants when greater reduction IOP is necessary.

PMID- 19574239
TI  - Accuracy of retinal thickness measurements obtained with Cirrus optical coherence
      tomography.
AB  - AIM: To report the frequency and severity of retinal thickness measurement errors
      in a Fourier domain optical coherence tomography (FDOCT) device, Cirrus OCT.
      METHODS: Data from 209 eyes undergoing Cirrus OCT imaging with the Macular Cube
      protocol were collected. For each eye, the position of the automated retinal
      boundary lines used by the Cirrus OCT software for thickness calculations was
      assessed using a 6-point categorical scale. The presence of errors was correlated
      with various parameters including: retinal morphological features and disease
      diagnosis. RESULTS: Errors of retinal boundary detection were observed in 57.5%
      of eyes but were severe in only 9.6% of eyes. The identification of subretinal
      fluid, subretinal tissue, pigment epithelium detachment or a diagnosis of
      choroidal neovascularisation was associated with more severe errors. Retinal
      cysts or a diagnosis of retinal vascular disease were less likely to be
      associated with significant error. CONCLUSIONS: Retinal thickness measurement
      errors appear to occur less frequently with Fourier domain OCT (Cirrus OCT), but
      segmentation errors remain a concern, particularly in assessment of eyes with
      structurally complex retinal disease. With the recent release of multiple FDOCT
      systems, assessment of segmentation error may be an important factor in
      determining the relative merits of these systems.

PMID- 19574240
TI  - Microbiological and clinical profiles of patients with microbial keratitis
      residing in nursing homes.
AB  - AIM: To study the microbiological and clinical profile of patients with microbial
      keratitis living in nursing homes. METHODS: A retrospective analysis of hospital
      records from 1996 to 2006 of patients who had microbial keratitis, and were
      living in nursing homes, was undertaken. The main parameters evaluated were
      clinical and microbiological profile and final visual outcome. RESULTS: Of 66
      patients included in this study, 39 were female and 27 were male, with mean age
      of 81(SD 11) (range 46-97) years. The major ocular and systemic factors
      associated with the occurrence of microbial keratitis were the presence of dry
      eyes (26%) and rheumatoid arthritis (81%), respectively. A positive bacterial
      culture was obtained in 54 (82%) cases with Staphylococcus being the most
      prevalent isolate (48%). Seven patients had positive culture for herpes virus.
      Surgical intervention had to be performed in 31(47%) of cases mainly in the form
      of botox injection for induction of ptosis (n = 9, 27%), keratoplasty (n = 8,
      24%), tarsorrhaphy (n = 5, 15%) or glue (n = 3, 9%). The mean pre-treatment and
      post-treatment visual acuity was counting fingers and 6/60 respectively.
      CONCLUSIONS: Microbial keratitis in patients living in nursing homes is usually
      caused by Staphylococcus and is associated with dry eyes and ocular surface
      disease. Surgical intervention is required in majority of cases with poor visual
      outcome.

PMID- 19574241
TI  - Influenza A (H1N1) infections among healthcare workers: a cause for cautious
      optimism.

PMID- 19574242
TI  - Screening for Chlamydia trachomatis in secondary schools, family planning and
      occupational health centres in Luxembourg.
AB  - BACKGROUND: We conducted a prospective pilot screening study in three settings in
      Luxembourg where routine urine testing is carried out independently for other
      purposes with a short sexual behaviour questionnaire to estimate prevalence and
      determine risk factors of urogenital Chlamydia trachomatis infection. METHODS:
      Screening was offered to sexually active volunteer participants aged less than 25
      years in three settings: i) women in three family planning centres (FPC), ii)
      young women and men in 29 secondary schools and iii) women and men in an
      occupational health centre (OHC) for newly recruited employees and workers. First
      catch urine samples were tested using the COBAS Amplicor and an in-house assay.
      Multiple logistic regression was performed to analyse risk factors. RESULTS:
      Overall prevalence among 4141 participants was 7.7% (95% CI 6.3 to 9.2) in FPCs,
      1.9% (95% CI 1.2 to 2.8) in secondary schools and 4.5% (95% CI 3.5 to 5.6) in the
      OHC. Depending on the setting, identified risk factors included being 18-22 years
      old, female sex, having three or more sexual partners in the past year and
      inconsistent condom use CONCLUSION: Screening is feasible in the three settings,
      but the prevalence of C trachomatis infection among men and women is highest in
      age groups that have left secondary school. Family planning centres were the
      setting with the highest C trachomatis prevalence and the only setting in our
      study able to provide case management, follow-up and repeat testing.

PMID- 19574244
TI  - Characteristics of ovarian cancer in women residing in Aotearoa, New Zealand:
      1993-2004.
AB  - BACKGROUND: Few studies have compared ovarian cancer rates between different
      ethnic groups in the same country. The aim of this study was to describe ethnic
      patterns in the incidence and mortality of ovarian cancer in New Zealand, and to
      investigate ethnic and socioeconomic differences in the grade and stage of
      ovarian cancer. METHODS: Data on all women registered with ovarian cancer on the
      New Zealand Cancer Registry (1993-2004) were analysed. Population data were taken
      from the 1996 and 2001 census. Logistic regression was used to estimate
      associations between ethnicity, deprivation and tumour characteristics. RESULTS:
      Age-standardised incidence rates were highest in Pacific women, intermediate in
      Maori women, and lowest in non-Maori, non-Pacific women. Age-standardised
      mortality rates showed the same pattern. Ovarian cancer subtypes differed by
      ethnic group. There was no significant association between socioeconomic
      deprivation and tumour grade or stage. Age-adjusted models showed that Maori
      women were more likely to have well-differentiated tumours and less likely to
      present at a later stage compared to non-Maori, non-Pacific women. These patterns
      were partly explained by socioeconomic deprivation, and were not apparent for
      Pacific women. CONCLUSIONS: Pacific and Maori women experience higher incidence
      of ovarian cancer and mortality, compared to non-Maori, non-Pacific women. Maori
      women seemed to have better prognostic factors (local stage and well
      differentiated tumours) than non-Maori, non-Pacific women. More work is needed to
      improve current cancer prevention strategies, particularly in Pacific women.

PMID- 19574243
TI  - Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative
      bacteria from patients with cystic fibrosis.
AB  - BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in
      patients with cystic fibrosis (CF). Current infection control guidelines aim to
      prevent transmission via contact and respiratory droplet routes and do not
      consider the possibility of airborne transmission. It was hypothesised that
      subjects with CF produce viable respirable bacterial aerosols with coughing.
      METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with
      CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system
      enabled fractioning of respiratory particles of different sizes and culture of
      viable Gram-negative non-fermentative bacteria. Cough aerosols were collected
      during 5 min of voluntary coughing and during a sputum induction procedure when
      tolerated. Standardised quantitative culture and genotyping techniques were used.
      RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of
      whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols
      were indistinguishable by molecular typing. In four cases the same genotype was
      isolated from ambient room air. Approximately 70% of viable aerosols collected
      during voluntary coughing were of particles <or=3.3 microm aerodynamic diameter.
      P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and
      Achromobacter xylosoxidans were cultivated from respiratory particles in this
      size range. Positive room air samples were associated with high total counts in
      cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with
      higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher
      quantitative sputum culture results (r = 0.58, p = 0.008). CONCLUSION: During
      coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram
      negative bacteria of respirable size range, suggesting the potential for airborne
      transmission.

PMID- 19574245
TI  - Inclusion of indigenous and ethnic minority populations in intervention trials:
      challenges and strategies in a New Zealand supermarket study.
AB  - BACKGROUND: The Supermarket Healthy Options Project (SHOP) is a large,
      randomised, controlled trial designed to evaluate the effect of tailored
      nutrition education and price discounts on supermarket food purchases. A key
      objective was to recruit approximately equal numbers of Maori, Pacific and non
      Maori, non-Pacific shoppers. This paper describes the recruitment strategies used
      and evaluates their impact on recruitment of Maori, Pacific and non-Maori, non
      Pacific trial participants. METHODS: Trial recruitment strategies included mailed
      invitations to an electronic register of supermarket customers; in-store targeted
      recruitment; and community-based recruitment. RESULTS: Of the 1103 total trial
      randomisations for whom ethnicity was known, 247 (22%) were Maori, 101 (9%)
      Pacific and 755 (68%) were non-Maori, non-Pacific shoppers. Mailed invitations
      produced the greatest proportion of randomisations (73% vs 7% in-store, and 20%
      from community recruitment). However, in-store and community recruitment were
      essential to boost Maori and Pacific samples. The cost of mailout (NZ$40 (14
      pounds) per randomised participant) was considerably less than the cost of
      community and in-store recruitment (NZ$301 (105 pounds) per randomised
      participant). CONCLUSIONS: The findings demonstrate considerable challenges and
      cost in recruiting indigenous and minority ethnic participants into intervention
      trials. Researchers and funding organisations should allocate more resources to
      recruitment of indigenous and minority populations than to recruitment of
      majority populations. Community recruitment and networks appear to be better ways
      to recruit these populations than passive strategies like mailouts.

PMID- 19574246
TI  - Heterogeneity by age in educational inequalities in cause-specific mortality in
      women in the Region of Madrid.
AB  - BACKGROUND: Within Europe, women in the southern regions have the lowest
      inequalities in mortality. This study evaluates inequalities in mortality from
      different causes by educational level and their contribution to total mortality
      inequalities in adult women in one of these regions. METHODS: The 2001 population
      census in the Region of Madrid was linked with deaths in the following 20 months
      according to the mortality registry. The population of women was stratified into
      three age groups, and the mortality rate ratio and mortality rate difference by
      educational level were estimated in each age group. The contribution of each
      cause of death to total mortality inequality was estimated based on the absolute
      index of inequality. RESULTS: In women aged 45-64 years, no significant relation
      was observed between educational level and mortality from the leading causes of
      death. In women aged 25-44 years and in those aged 65 and over, the mortality
      rate ratios and differences from the leading causes of death gradually increased
      from the highest to the lowest educational level. AIDS, respiratory diseases and
      digestive diseases, in young adult women, and cardiovascular diseases, in older
      women, were the causes of death that contributed most to inequality in mortality.
      CONCLUSIONS: At the beginning of the twenty-first century, mortality inequalities
      by educational level were not seen in middle-aged adult women in the Region of
      Madrid. In contrast, mortality inequalities were found in young women and in
      older women, although the main causes of death that contributed to these
      inequalities were different in each group.

PMID- 19574247
TI  - Alcohol consumption and use of acute and mental health hospital services in the
      West of Scotland Collaborative prospective cohort study.
AB  - BACKGROUND: Overconsumption of alcohol affects health. Data from men from the
      West of Scotland Collaborative study were analysed to see how reported alcohol
      was related to acute and mental health hospital admissions. METHODS: Men (N =
      5772) from a prospective cohort study located in 27 workplaces in West and
      Central Scotland were screened when aged 35-64 in 1970-3. The number of acute and
      mental health admissions and bed-days were calculated by alcohol category (none,
      1-7, 8-14, 15-21, 22-34 and 35 or more units per week) to the end of 2005.
      Specific causes were coronary heart disease (CHD), stroke, respiratory diseases
      and alcohol-related. RESULTS: Men who consumed 22 or more units per week had a
      20% higher rate of acute admissions than non-drinkers. The number of bed-days
      were higher for men drinking eight or more units and increased with consumption,
      with the highest category having a 58% higher rate of bed-days than non-drinkers.
      Non-drinkers had the highest admissions for CHD. For stroke, drinkers of 15 or
      more units had higher admissions and higher number of bed-days and these
      increased with increasing consumption. Respiratory admissions were higher for
      drinkers of 22 or more units and bed-days were higher for drinkers of 15 or more
      units. Alcohol-related admissions and number of bed-days generally increased with
      consumption. Mental health admissions and number of bed-days were raised for
      drinkers of 22 or more units with a suggestion of a J-shaped relationship.
      CONCLUSION: Alcohol consumption has a substantial effect on acute and mental
      health admissions and bed-days.

PMID- 19574248
TI  - Cognitive ability in adolescence and mortality in middle age: a prospective life
      course study.
AB  - BACKGROUND: An association between childhood cognitive ability measured by IQ
      tests and mortality has been reported recently. It is not clear from those
      studies to what extent the increased relative risk associated with lower IQ
      scores may be attenuated by adjustment for other risk factors. This study aims to
      investigate the association between cognitive ability measured at age 18-20 years
      and mortality among middle-aged men adjusting for risk factors for mortality over
      the life course. METHODS: Data on cognitive ability, and other risk factors for
      premature mortality (indicators of mental health and social adjustment and
      behavioural factors), were collected among 49 321 men, born in 1949-51, at
      conscription for compulsory military training in 1969-70. Information on
      socioeconomic factors in childhood and adulthood, as well as information on
      mortality, was collected through national registers. RESULTS: Cognitive ability
      showed an inverse and graded association with mortality between 40 and 53 years
      of age (1297 cases, crude hazard ratio (HR) 1.15, 95% CI 1.12 to 1.18, for one
      point decrease on the nine-point IQ scale). Adjustment for indicators of social
      misbehaviour, mental health problems and behavioural risk factors, measured in
      late adolescence, and adult social circumstances strongly attenuated the
      increased risks of mortality, and it was no longer significantly increased
      (adjusted HR 1.02, 95% CI 0.99 to 1.06, for one-point decrease on the nine-point
      IQ scale). CONCLUSION: The association between IQ and mortality among men below
      54 years of age was almost completely attenuated by adjustment for risk factors
      captured by our measures of achieved social positions.

PMID- 19574249
TI  - Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose)
      polymerase-1 is required for mitochondrial cell death induced by triterpenoid
      pristimerin in human cervical cancer cells.
AB  - Naturally occurring triterpenoid compounds have long been used as anti
      inflammatory, antimalarial, and insecticidal agents. It has become evident that
      some of the natural or synthetic triterpenoids have promising clinical potential
      as both a therapeutic and chemopreventive agent for cancer. However, the
      molecular basis for the antitumor activity of triterpenoid has yet to be defined.
      In this study, we show that pristimerin, a natural triterpenoid, induces
      mitochondrial cell death in human cervical cancer cells and that reactive oxygen
      species (ROS)-dependent activation of both Bax and poly(ADP-ribose) polymerase-1
      (PARP-1) is critically required for the mitochondrial dysfunction. We also showed
      that c-Jun N-terminal kinase (JNK) is involved in ROS-dependent Bax activation.
      Treatment of pristimerin induced an increase in intracellular ROS, JNK
      activation, conformational change, and mitochondrial redistribution of Bax,
      mitochondrial membrane potential loss, and cell death. The PARP-1 was also found
      to be activated by pristimerin treatment. An antioxidant, N-acetyl-l-cysteine
      (NAC), inhibited pristimerin-induced JNK activation, Bax relocalization, and PARP
      1 activation, as well as mitochondrial cell death. Moreover, inhibition of JNK
      clearly suppressed conformational change and mitochondrial translocation of Bax
      and subsequent mitochondrial cell death but did not affect PARP-1 activation.
      Inhibition of PARP-1 with 1,5-dihydroxyisoquinoline (DIQ) or with small
      interfering RNA of PARP-1 significantly attenuated pristimerin-induced
      mitochondrial membrane potential loss and cell death but did not affect JNK
      activation and Bax relocalization. These results indicate that the natural
      triterpenoid pristimerin induces mitochondrial cell death through ROS-dependent
      activation of both Bax and PARP-1 in human cervical cancer cells and that JNK is
      involved in ROS-dependent Bax activation.

PMID- 19574250
TI  - The kiwifruit lycopene beta-cyclase plays a significant role in carotenoid
      accumulation in fruit.
AB  - The composition of carotenoids, along with anthocyanins and chlorophyll, accounts
      for the distinctive range of colour found in the Actinidia (kiwifruit) species.
      Lutein and beta-carotene are the most abundant carotenoids found during fruit
      development, with beta-carotene concentration increasing rapidly during fruit
      maturation and ripening. In addition, the accumulation of beta-carotene and
      lutein is influenced by the temperature at which harvested fruit are stored.
      Expression analysis of carotenoid biosynthetic genes among different genotypes
      and fruit developmental stages identified Actinidia lycopene beta-cyclase (LCY
      beta) as the gene whose expression pattern appeared to be associated with both
      total carotenoid and beta-carotene accumulation. Phytoene desaturase (PDS)
      expression was the least variable among the different genotypes, while zeta
      carotene desaturase (ZDS), beta-carotene hydroxylase (CRH-beta), and epsilon
      carotene hydroxylase (CRH-epsilon) showed some variation in gene expression. The
      LCY-beta gene was functionally tested in bacteria and shown to convert lycopene
      and delta-carotene to beta-carotene and alpha-carotene respectively. This
      indicates that the accumulation of beta-carotene, the major carotenoid in these
      kiwifruit species, appears to be controlled by the level of expression of LCY
      beta gene.

PMID- 19574252
TI  - Symbolism of plants: examples from European-Mediterranean culture presented with
      biology and history of art.

PMID- 19574251
TI  - Composite Medicago truncatula plants harbouring Agrobacterium rhizogenes
      transformed roots reveal normal mycorrhization by Glomus intraradices.
AB  - Composite plants consisting of a wild-type shoot and a transgenic root are
      frequently used for functional genomics in legume research. Although
      transformation of roots using Agrobacterium rhizogenes leads to morphologically
      normal roots, the question arises as to whether such roots interact with
      arbuscular mycorrhizal (AM) fungi in the same way as wild-type roots. To address
      this question, roots transformed with a vector containing the fluorescence marker
      DsRed were used to analyse AM in terms of mycorrhization rate, morphology of
      fungal and plant subcellular structures, as well as transcript and secondary
      metabolite accumulations. Mycorrhization rate, appearance, and developmental
      stages of arbuscules were identical in both types of roots. Using Mt16kOLI1Plus
      microarrays, transcript profiling of mycorrhizal roots showed that 222 and 73
      genes exhibited at least a 2-fold induction and less than half of the expression,
      respectively, most of them described as AM regulated in the same direction in
      wild-type roots. To verify this, typical AM marker genes were analysed by
      quantitative reverse transcription-PCR and revealed equal transcript accumulation
      in transgenic and wild-type roots. Regarding secondary metabolites, several
      isoflavonoids and apocarotenoids, all known to accumulate in mycorrhizal wild
      type roots, have been found to be up-regulated in mycorrhizal in comparison with
      non-mycorrhizal transgenic roots. This set of data revealed a substantial
      similarity in mycorrhization of transgenic and wild-type roots of Medicago
      truncatula, validating the use of composite plants for studying AM-related
      effects.

PMID- 19574253
TI  - Environmental control of sepalness and petalness in perianth organs of
      waterlilies: a new Mosaic theory for the evolutionary origin of a differentiated
      perianth.
AB  - The conventional concept of an 'undifferentiated perianth', implying that all
      perianth organs of a flower are alike, obscures the fact that individual perianth
      organs are sometimes differentiated into sepaloid and petaloid regions, as in the
      early-divergent angiosperms Nuphar, Nymphaea, and Schisandra. In the waterlilies
      Nuphar and Nymphaea, sepaloid regions closely coincide with regions of the
      perianth that were exposed when the flower was in bud, whereas petaloid regions
      occur in covered regions, suggesting that their development is at least partly
      controlled by the environment of the developing tepal. Green and colourful areas
      differ from each other in trichome density and presence of papillae, features
      that often distinguish sepals and petals. Field experiments to test whether
      artificial exposure can induce sepalness in the inner tepals showed that
      development of sepaloid patches is initiated by exposure, at least in the
      waterlily species examined. Although light is an important environmental cue,
      other important factors include an absence of surface contact. Our interpretation
      contradicts the unspoken rule that 'sepal' and 'petal' must refer to whole
      organs. We propose a novel theory (the Mosaic theory), in which the distinction
      between sepalness and petalness evolved early in angiosperm history, but these
      features were not fixed to particular organs and were primarily environmentally
      controlled. At a later stage in angiosperm evolution, sepaloid and petaloid
      characteristics became fixed to whole organs in specific whorls, thus reducing or
      removing the need for environmental control in favour of fixed developmental
      control.

PMID- 19574254
TI  - OXI1 protein kinase is required for plant immunity against Pseudomonas syringae
      in Arabidopsis.
AB  - Expression of the Arabidopsis Oxidative Signal-Inducible1 (OXI1) serine/threonine
      protein kinase gene (At3g25250) is induced by oxidative stress. The kinase is
      required for root hair development and basal defence against the oomycete
      pathogen Hyaloperonospora parasitica, two separate H(2)O(2)-mediated processes.
      In this study, the role of OXI1 during pathogenesis was characterized further.
      Null oxi1 mutants are more susceptible to both virulent and avirulent strains of
      the biotrophic bacterial pathogen Pseudomonas syringae compared with the wild
      type, indicating that OXI1 positively regulates both basal resistance triggered
      by the recognition of pathogen-associated molecular patterns, as well as effector
      triggered immunity. The level of OXI1 expression appears to be critical in
      mounting an appropriate defence response since OXI1 overexpressor lines also
      display increased susceptibility to biotrophic pathogens. The induction of OXI1
      after P. syringae infection spatially and temporally correlates with the
      oxidative burst. Furthermore, induction is reduced in atrbohD mutants and after
      application of DPI (an inhibitor of NADPH oxidases) suggesting that reactive
      oxygen species produced through NADPH oxidases drives OXI1 expression during this
      plant-pathogen interaction.

PMID- 19574255
TI  - Flow-cycled versus time-cycled sIPPV in preterm babies with RDS: a breath-to
      breath randomised cross-over trial.
AB  - OBJECTIVES: Few data exist about patient-triggered ventilation techniques in
      neonatal critical care. Our aim was to compare pressure-limited synchronised
      intermittent positive pressure (or assist/control) ventilation (sIPPV) in the
      classical time-cycled (TC-sIPPV) mode against flow-cycled (FC-sIPPV) modality. In
      this latter, typical sIPPV full respiratory support is provided but both the
      initiation and the end of inflation are determined by the infant's spontaneous
      respiratory efforts by using airway flow changes. SETTING: A third-level neonatal
      intensive care unit. PATIENTS AND INTERVENTION: Ten preterm babies (<32 weeks'
      gestation) were randomised to receive 1 h FC-sIPPV followed by 1 h TC-sIPPV or
      the inverse shift, according to a computer-created randomisation table. Eligible
      babies had hyaline membrane disease and received 200 mg/kg surfactant at least 6
      h before the study period. Respiratory mechanics, ventilatory and vital parameter
      data were registered real time. RESULTS: FC-sIPPV resulted in lower-rate volume
      ratio, pressure x rate product, mean airway pressure and heart rate; tidal volume
      and oxygen saturation were higher (all p<0.001). Spontaneous inspiratory time was
      lower than usually set by the physician and it was directly correlated to birth
      weight (rho = 0.5, p = 0.001) and gestational age (rho = 0.32, p = 0.001). No
      differences were noticed in the mechanics and blood gas and vital parameters
      during the two study phases. CONCLUSIONS: FC-sIPPV may safely result in a better
      patient ventilator synchrony. Inspiratory time usually set in neonatal critical
      care is higher than that decided by the baby during spontaneous effort. This
      should be considered when establishing time-cycled ventilation.

PMID- 19574256
TI  - Analgesics, sedatives and neuromuscular blockers as part of end-of-life decisions
      in Dutch NICUs.
AB  - BACKGROUND: Clinicians frequently administer analgesics and sedatives at the time
      of withholding or withdrawal of life-sustaining treatment in newborns. This
      practice might be regarded as intentionally hastening of death. OBJECTIVE: To
      describe type, doses and reasons for administering medications as part of end-of
      life decisions in the Dutch neonatal intensive care units. DESIGN AND SETTING: We
      reviewed the medical files of 340 newborn deaths with a preceding end-of-life
      decision over a 12-month period to describe the use of analgesics, sedatives
      and/or neuromuscular blockers. The neonatologists of 147 of the 150 newborns with
      a preceding end-of-life decision based on the infant's poor prognosis were
      interviewed to obtain additional details about the use of medication. RESULTS:
      Analgesics and sedatives were administered to 224 of 340 newborns before the end
      of-life decision and to 292 newborns after the decision. The medication was
      increased in 94 of 289 newborns whose death was imminent and in 110 of 150
      newborns with a poor prognosis. Reasons for the increase were treatment of pain
      and suffering, and in 4% of cases hastening of death. Reasons were undocumented
      in 55% of deaths. Neuromuscular blockers were administered in 16% of patients
      because they already received these agents or to stop or prevent gasping.
      CONCLUSIONS: Analgesics and sedatives are generally increased after the end-of
      life decision to treat pain and suffering and rarely to hasten death.
      Neuromuscular blockers were administered in 16% of deaths. Medical files provide
      insufficient documentation of considerations leading to the increase of
      medication, which hinders (external) review.

PMID- 19574257
TI  - Plasma aminotransferase concentrations in preterm infants.
AB  - The aim of this study was to generate reference ranges for aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) in preterm infants by
      describing the observed plasma concentration of these enzymes in babies born
      between 22 and 36 weeks' gestation. A service evaluation was conducted in babies
      admitted to two large neonatal intensive care units in the UK. 7006 blood samples
      from 1860 infants admitted to the two units between 2004 and 2008 were included.
      Extremely premature infants had high plasma enzyme activities when compared to
      babies at a later corrected gestational age. This may be due to more severe
      illness immediately after birth.

PMID- 19574258
TI  - Seasonal carbon storage and growth in Mediterranean tree seedlings under
      different water conditions.
AB  - In all Mediterranean-type ecosystems, evergreen and deciduous trees differing in
      wood anatomy, growth pattern and leaf habit coexist, suggesting distinct
      adaptative responses to environmental constraints. This study examined the
      effects of summer water stress on carbon (C) storage and growth in seedlings of
      three coexisting Mediterranean trees that differed in phenology and wood anatomy
      characteristics: Quercus ilex subsp. ballota (Desf.) Samp., Quercus faginea Lam.
      and Pinus halepensis L. Seedlings were subjected to two levels of watering during
      two consecutive summers and achieved a minimum of -0.5 and -2.5 MPa of predawn
      water potential in the control and water stress treatment, respectively. Both
      Quercus species concentrated their growth in the early growing season, demanding
      higher C in early spring but replenishing C-stores in autumn. These species
      allocated more biomass to roots, having larger belowground starch and lipid
      reserves. Quercus species differed in seasonal storage dynamics from P.
      halepensis. This species allocated most of its C to aboveground growth, which
      occurred gradually during the growing season, leading to fewer C-reserves.
      Soluble sugar and starch concentrations sharply declined in August in P.
      halepensis, probably because reserves support respiration demands as this species
      closed stomata earlier under water stress. Drought reduced growth of the three
      species, mainly in Q. faginea and P. halepensis, but not C-reserves, suggesting
      that growth under water stress conditions is not limited by C-availability.

PMID- 19574259
TI  - Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense
      and codon deletion in the acetyltransferase domain, correlates with ESCO2
      expression and establishes the clinical criteria for Roberts syndrome.
AB  - BACKGROUND: Roberts syndrome (RBS) and SC phocomelia are caused by mutations in
      ESCO2, which codes for an acetyltransferase involved in the regulation of sister
      chromatid cohesion. Of 26 mutations described to date, only one missense mutation
      has been reported and all others are predicted to be truncating mutations.
      Genotype-phenotype analysis has been hampered by limited numbers of patients with
      clinical information available. OBJECTIVE: To provide unpublished clinical data
      for 31 patients with proven ESCO2 mutations and combine this series with
      previously reported clinical and mutation data on 18 cases. Methods Genotype
      phenotype correlations and functional effects of two novel ESCO2 mutations were
      analysed. In situ hybridisation on human embryos at Carnegie stages 14, 17 and 21
      was performed to study ESCO2 expression during development. RESULTS AND
      CONCLUSIONS: Using the cohort of 49 patients, the clinical criteria for RBS were
      delineated to include: growth retardation; symmetric mesomelic shortening of the
      limbs in which the upper limbs are more commonly and severely affected than the
      lower limbs; characteristic facies with microcephaly. The severity of
      malformations of the facies correlates with the severity of limb reduction. The
      occurrence of corneal opacities may be associated with specific mutations. Two
      new mutations, both in the ESCO2 acetyltransferase domain, are described and
      their acetylation effects in vitro demonstrated. In situ hybridisation on human
      embryos showed ESCO2 expression in the brain, face, limb, kidney and gonads,
      which corresponds to the structures affected in RBS.

PMID- 19574261
TI  - Encephalocraniocutaneous lipomatosis.
AB  - BACKGROUND: Encephalocraniocutaneous lipomatosis (ECCL) is a sporadically
      occurring neurocutaneous disorder of unknown aetiology. It has repeatedly been
      discussed as a localised form of Proteus syndrome. In 2006, the first large
      series of patients was reported, and diagnostic criteria were proposed. AIMS: To
      better define the phenotypic spectrum and natural history of ECCL and to revise
      diagnostic criteria. METHODS: 54 patients with ECCL were reviewed. RESULTS: Eye
      anomalies (mainly choristomas) and skin lesions (non-scarring alopecia, naevus
      psiloliparus, subcutaneous fatty masses, nodular skin tags, aplastic scalp
      defects) may be unilateral or bilateral and occur in a consistent pattern.
      Central nervous system anomalies consist of intracranial and intraspinal lipomas,
      congenital abnormalities of the meninges, and putative focal vascular defects
      resulting in highly asymmetrical changes. About two-thirds of patients have a
      normal development or mild retardation only, and half of them have seizures. No
      correlation between the extent of central nervous system anomalies and
      neurological features could be established. Aortic coarctation, progressive bone
      cysts and jaw tumours may be associated. CONCLUSIONS: Revised diagnostic criteria
      are proposed. ECCL is considered to differ from Proteus syndrome in particular,
      but oculoectodermal syndrome is possibly a mild variant. Pathogenetically,
      mosaicism for a mutated autosomal gene involved in multiple mesenchymal tumours
      and vasculogenesis, with or without a second hit event, is discussed.

PMID- 19574262
TI  - Is electrocardiography a reliable tool for identifying patients with isthmus
      dependent atrial flutter?
AB  - AIMS: To verify the reliability of the surface ECG to discriminate between
      cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) and non-CTI-AFL. METHODS
      AND RESULTS: We reviewed the ECGs of 186 consecutive patients who underwent
      catheter ablation of AFL between January 2004 and January 2008. The ECG pattern
      was defined typical for CTI-AFL, if F-waves were: (i) dominantly negative in the
      inferior leads and positive in V1 (CCW) or (ii) dominantly positive in the
      inferior leads and negative in V1 (CW). At the electrophysiological study (EPS),
      138 patients (74.2%) had a CTI-AFL and 48 patients (25.8%) had a non-CTI-AFL. A
      CTI-AFL was found not only in 90.5% of patients having a typical ECG, but also in
      40% of patients having an atypical ECG. Thus, a typical AFL ECG showed a
      sensitivity of 0.83 and a specificity of 0.75 to predict a CTI-AFL, with a
      positive predictive value of 90.5% and a negative predictive value of 60%.
      CONCLUSION: Typical AFL ECG is a good predictor of CTI-AFL, and in this case, an
      ablation procedure can be recommended. On the contrary, an atypical AFL ECG does
      not rule out a CTI-AFL; so, even in this group of patients, an EPS should not be
      denied when indicated by the clinical circumstances.

PMID- 19574260
TI  - Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert
      syndrome with congenital hepatic fibrosis).
AB  - OBJECTIVE: To identify genetic causes of COACH syndrome BACKGROUND: COACH
      syndrome is a rare autosomal recessive disorder characterised by Cerebellar
      vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia,
      Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid
      hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert
      syndrome related disorder (JSRD). METHODS: In a cohort of 251 families with JSRD,
      26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus
      clinically apparent liver disease. Diagnostic criteria for JSRD were clinical
      findings (intellectual impairment, hypotonia, ataxia) plus supportive brain
      imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced
      in all subjects for whom DNA was available. In COACH subjects without MKS3
      mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. RESULTS: 19/23
      families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%)
      with JSRD but no liver disease. Two other families with COACH carried CC2D2A
      mutations, one family carried RPGRIP1L mutations, and one lacked mutations in
      MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with
      mutations in one of the three genes, revealed changes within the congenital
      hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without
      liver disease, MKS3 mutations account for 21/232 families (9%). CONCLUSIONS:
      Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor
      contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene
      tested in patients with JSRD plus liver disease and/or coloboma, followed by
      CC2D2A and RPGRIP1L.

PMID- 19574263
TI  - Arrhythmias in heart transplant recipients.
AB  - The suture between the recipient and donor atrium in a heart transplant patient
      usually gives complete electric isolation. In this case report, we describe two
      transplant patients with an atrial tachycardia in the recipient atrium. In the
      first patient there was no conduction to the donor atrium, whereas the second
      patient had a breakthrough with 2-to-1 conduction.

PMID- 19574264
TI  - Aortic valve replacement with minimal extracorporeal circulation versus standard
      cardiopulmonary bypass.
AB  - The purpose of this study was to evaluate the safety and the clinical outcomes of
      aortic valve replacement (AVR) performed with minimally invasive extracorporeal
      circulation (miniECC) technique vs. standard cardiopulmonary bypass (CPB). From
      February 2006 to December 2007 a total of 181 isolated AVR were performed, of
      these 53 patients were operated using minimal extracorporeal circulation system
      and 128 patients were operated using the standard CPB. Demographic
      characteristics and operative data were similar in both groups except for
      EuroSCORE (P<0.0001). Operative mortality (<30 days) was 3.8% for miniECC group
      and 4.7% for CPB group (P=ns). Patients in both groups showed similar
      postoperative chest tube drainage (432+/-325 ml vs. 460+/-331 ml, P=ns). The
      percentage of transfused patients was similar in both groups (37.7% vs. 43.8%,
      P=0.45). The number of transfused blood bank products was higher in patients with
      a body surface area >1.7 m(2) and who underwent traditional CPB in respect to
      miniECC system. Postoperatively renal injury, atrial fibrillation episodes,
      neurologic event rate, ICU and hospital stay length were similar in both groups.
      The miniECC is suitable for AVR providing good clinical results but the present
      results should not identify the miniECC system to be superior to the conventional
      CPB.

PMID- 19574265
TI  - Reinforced closure of the sternum with absorbable pins for high-risk patients.
AB  - We report our result of the reinforced sternal closure in 51 consecutive
      patients. We applied a new type of absorbable radiopaque pins (Super FIXSORB)
      composed of poly-lactide acid and hydroxyapatite, in addition to conventional
      stainless steel wires. The risk scores of our patients were calculated from the
      simplified risk scoring system for major infection based on the Society of
      Thoracic Surgeons National Cardiac Database. The expected probability of
      infection is significantly higher than the actual infection rate in our patients.
      Our procedure may contribute to minimizing the fatal sternal complication
      particularly in high-risk patients.

PMID- 19574266
TI  - An analysis of WHO data on lethal violence: relevance of the New Western
      Millennium.
AB  - INTRODUCTION: Suicide and homicide are considered to be lethal violent acts with
      a clear difference in their directions, that is, inwardly "killing oneself" or
      outwardly "killing another," respectively. There are some studies in which these
      2 violent acts are considered under the same framework mostly within Western
      countries. This article for the first time investigates this issue throughout the
      world. Material and methods. The present study uses data that have been estimated
      by Global Burden of Disease (GBD) project for 2000 for the 6 different regions of
      the world proposed by WHO. The suicide/homicide ratio has been calculated by
      dividing the suicide rate by the sum of the suicide and homicide rates within
      each age and sex groups. Findings. Three distinct groups have emerged. In the
      first group, that is, Southeast Asia, Europe, and Western Pacific, lethal
      violence in both males and females usually directs inward whereas in the second
      group, that is, Africa, lethal violence in both males and females directs
      outward. In the third group, that is, America and Eastern Mediterranean, in males
      lethal violence generally directs outward whereas in females it often directs
      inward. CONCLUSION: Under the same framework if a factor causes external blame
      for the people's failures it will increase the likelihood that the
      suicide/homicide ratio is expressed as homicide and vice versa. Although this
      might explain the observed pattern to some extent, more in-depth studies are
      needed to better understand the causal root of the pattern.

PMID- 19574267
TI  - Exposure to secondhand smoke in infants: declining trends from 2001 to 2008?
AB  - OBJECTIVE: To define the trend in young children's exposure to parental
      secondhand smoke. METHODS: Secondary analysis of data was done on families of
      infants between the ages of 6 and 24 months that had been enrolled for 2 cross
      sectional studies in 2001 and 2008. RESULTS: Data from 648 families were
      analyzed. Overall, 29.8% of children had been exposed to parental secondhand
      smoke; 32% in 2001 and 27.4% in 2008, (P value >.05). In all cases, the source of
      exposure was the father; in 2008, 4 families reported both parents as being
      habitual smokers. Ratio of indoor to outdoor smokers was 2.92 in 2001 and 0.93 in
      2008. CONCLUSION: The decline in the percentage of infants exposed to parental
      smoking is nonsignificant; parental indoor smoking has decreased significantly
      but remains at unacceptably high levels. Authorities responsible for the health
      of young children need to revise interventional policies.

PMID- 19574268
TI  - Oral health status of Vietnamese adults: findings from the National Oral Health
      Survey of Vietnam.
AB  - BACKGROUND: The National Oral Health Survey of Vietnam 1999 was conducted to
      inform policy development. AIMS: This article aims to describe the oral health
      status, analyze its socioeconomic distribution, and evaluate change over time in
      the oral health of the adult population of Vietnam. METHODS: A multistaged
      stratified sampling process was used. Adults aged 18+ years completed a social
      survey and were examined by trained and calibrated dentists. RESULTS: Oral
      symptoms were frequent. Dental care utilization was low and mostly problem
      driven. One third of adults had periodontal pockets. Calculus was highly
      prevalent. Caries level was moderate with a mean decayed, missing, and filled
      teeth score of 4.98 (SD 5.7), with most as untreated decay. Factors related to
      caries were gender, hygiene practices, socioeconomic status, location, and dental
      visiting. CONCLUSIONS: The oral health status of the Vietnamese adult population
      was compromised by various factors. There was indication of deteriorating oral
      health of this population.

PMID- 19574269
TI  - Oral health status of Vietnamese children: findings from the National Oral Health
      Survey of Vietnam 1999.
AB  - The National Oral Health Survey of Vietnam 1999 was conducted to inform policy
      development. AIMS: The aims were to describe the oral health status, to analyze
      its socioeconomic distribution, and to evaluate change over time in the oral
      health of Vietnamese children. METHODS: A multistaged stratified sampling process
      was employed. Children aged 6 to 17 years were examined by trained and calibrated
      dental examiners. A parental questionnaire was used. Drinking water was analyzed.
      RESULTS: Preventive oral health behaviors and dental care utilization were
      infrequent. The decayed, missing, and filled surfaces referring to primary
      dentition (dmfs) and permanent dentition (DMFS) scores (SD) were 8.9 (11.3) and
      2.5 (4.4), respectively. Primary caries experience was associated with fluoride
      level in drinking water, age, gender, residential status, and geographical
      location. Permanent caries was also associated with dental visiting and parental
      education. There was an increase in the prevalence of dental caries in the
      Vietnamese child population compared with 10 years earlier. CONCLUSION: The oral
      health of Vietnamese children was characterized by high level of dental caries
      with variation among socioeconomic groups. It suggests the need for a population
      oral health program that includes measures to target high-need children.

PMID- 19574270
TI  - Roles of parents in preventing dental caries in the primary dentition among
      preschool children in Thailand.
AB  - This study aimed to identify important roles of parents in preventing caries in
      primary dentition among preschool children in Thailand. A total of 664 preschool
      children aged 3 to 4 years and their parents were sampled from representative
      provinces of the 5 regions of Thailand. Dental examination to assess dental
      caries in preschool children was conducted. Questionnaires investigating roles of
      parents in caring for their children's teeth were used to interview parents.
      Preschool children were more likely to have at least 1 carious tooth if parents
      did not always clean their teeth every time they bathed them, did not always
      examine the cleanliness of children's teeth regularly, and always allowed
      children to consume snacks more than 3 times a day. Thai parents must be
      motivated to consistently spend the time required to take care of the primary
      dentition of their children by regular cleaning and controlling the snacking
      behavior of children.

PMID- 19574271
TI  - Prevalence of and factors associated with cigarette smoking among university
      students: a study from Iran.
AB  - To determine the prevalence of cigarette use among college students and to
      identify correlates of cigarette smoking, a cross-sectional study was conducted
      on 1750 college students in the city of Kerman, located in southern Iran. The
      average age of college students was 21.2 +/- 2.1 years. A total of 52%
      participants were female, 92% were single, and 11% (184) were smokers (22% of men
      and 2.4% of women). The average age of smoking initiation was 15.9 +/- 4.5 years.
      A high association was shown with the use of cigarettes among close friends (odds
      ratio [OR] = 4.3), alcohol use (OR = 2.95), and being a male (OR = 2.81). Less
      cigarette use was shown among participants who prayed (OR = 0.52) and those with
      better academic standing (OR = 0.68). Based up the high prevalence of cigarette
      use among college students and also taking into account the correlates of
      cigarette use, gender-specific programs need to be tailored for cigarette use
      prevention among college students.

PMID- 19574272
TI  - Challenges for injury prevention among the elderly in Kazakhstan.
AB  - Injury prevention is one of the most important issues facing governmental public
      health programs today. Injuries lead to premature mortality and disability of the
      population, decrease quality of life, and damage community property. Data
      demonstrate that 54.1% of domestic (household related) and traffic injuries among
      the elderly were caused by a general lowering of attention and inadequate caution
      associated with increased age. This shows the necessity for the development of
      injury-prevention programs targeting the elderly. Currently, several different
      types of institutions working in areas such as public health, promotion of
      healthy lifestyles, social and clinical medicine are engaged in a period of
      detailed study of the injury status and discussion of strategies to implement
      injury prevention programs among the elderly. These programs must be oriented
      toward both the creation of safe injury-free environments and to actively engage
      the elderly to increase overall physical fitness to increase self-injury
      protection.

PMID- 19574273
TI  - The role of schools of public health: learning from history, looking to the
      future.
AB  - There is a broad consensus on the need for high-quality public health education
      and research to tackle the world's many public health challenges. Public health
      education and research are delivered by a variety of institutions operating very
      different models, which collectively can be called schools of public health.
      Given the importance of education and research to public health systems, it is
      surprising how little research has been done to assess the role of schools of
      public health in contributing to population health. In particular, it is notable
      there has been very little research on the strengths and weaknesses of the
      different models of schools of public health that have evolved over the last 100
      years. Thus, a historical perspective is crucial. To date most historical work
      has focused on US schools of public health. Although the evidence is patchy, a
      global overview of the history of schools of public health identifies three
      important themes: capacity building, multidisciplinarity and balancing teaching
      and research. Newer challenges and opportunities include addressing the impact of
      climate change and developments in e-learning. Schools of public health have the
      potential to make a central contribution to progress in public health practice in
      the twenty-first century.

PMID- 19574274
TI  - False-positive mammography and depressed mood in a screening population: findings
      from the New Hampshire Mammography Network.
AB  - BACKGROUND: False positives occur in approximately 11% of screening mammographies
      in the USA and may be associated with psychologic sequelae. METHODS: We sought to
      examine the association of false-positive mammography with depressed mood among
      women in a screening population. Using data from a state-based mammography
      registry, women who completed a standardized questionnaire between 7 May 2001 and
      2 June 2003, a follow-up questionnaire between 19 June 2003 and 8 October 2004
      and who received at least one screening mammogram during this interval were
      identified. False positives were examined in relation to depressed mood. RESULTS:
      Eligibility criteria were met by 13 491 women with a median age of 63.9 (SD =
      9.6). In the study population, 2107 (15.62%) experienced at least one false
      positive mammogram and 450 (3.34%) met criteria for depressed mood. Depressed
      mood was not significantly associated with false positives in the overall
      population [OR = 0.96; 95% confidence interval (CI) = 0.72-1.28], but this
      association was seen among Non-White women (OR = 3.23; 95% CI = 1.32-7.91).
      CONCLUSION: Depressed mood may differentially affect some populations as a harm
      associated with screening mammography.

PMID- 19574275
TI  - Internationally recognized guidelines for 'sensible' alcohol consumption: is
      exceeding them actually detrimental to health and social circumstances? Evidence
      from a population-based cohort study.
AB  - BACKGROUND: The health and social impact of drinking in excess of internationally
      recognized weekly (>21 units in men; >14 units in women) and daily (>4 units in
      men; >3 units in women) recommendations for 'sensible' alcohol intake are largely
      unknown. METHODS: A prospective cohort study of 1551 men and women aged around 55
      years in 1988 when typical alcohol consumption was recalled using a 7-day grid.
      An average of 3.4 years later (1990/92), study participants were re-surveyed (n =
      1259; 84.7% of the target population) when they responded to nurse-administered
      enquiries regarding minor psychiatric morbidity, self-perceived health,
      hypertension, accidents, overweight/obesity and financial difficulties. Study
      members were followed up for mortality experience over 18 years. RESULTS: In
      fully adjusted analyses, surpassing guidelines for sensible alcohol intake was
      associated with an increased risk of hypertension [daily guidelines only: P
      value(trend): 0.012], financial problems [weekly guidelines: P-value(difference):
      0.046] and, to a lesser degree, accidents [weekly guidelines: P
      value(difference): 0.065]. There was no association between either indicator of
      alcohol intake and mortality risk. CONCLUSIONS: In the present study, there was
      some evidence for a detrimental effect on health and social circumstances of
      exceeding current internationally recognized weekly and daily guidelines for
      alcohol intake.

PMID- 19574276
TI  - Assessment of chromosomal integrity using a novel live-cell imaging technique in
      mouse embryos produced by intracytoplasmic sperm injection.
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a technique in which sperm
      are injected directly into unfertilized oocytes, whereby offspring can be
      obtained even with dysfunctional sperm. Despite its advantages in human and
      animal reproductive technology, the low rate of resultant live offspring is
      perturbing. One major cause is thought to be embryonic chromosomal abnormalities.
      However, there is no direct evidence of how these occur or how they affect
      pregnancy outcomes. METHODS: Chromosomal dynamics during the first mitotic
      division of mouse embryos were analyzed using a new live-cell imaging technology.
      After imaging, the embryos' developmental capacities were determined. RESULTS:
      When ICSI-generated embryos were monitored for their chromosome integrity, some
      embryos with apparent normal morphology seen by conventional light microscopy had
      abnormal chromosome segregation (ACS) at the first mitotic division. Chromosomal
      fragments were misaligned during the first metaphase and formed micronuclear-like
      structures at the interphase of the 2-cell stage. Similar ACS was also found in
      mouse embryos produced by microinjecting round spermatids, with even higher
      frequency. Giemsa staining and immunostaining revealed that these fragments were
      derived from double-strand DNA breaks in the paternal genome. About half of the
      embryos with ACS developed into normal-looking morulae or blastocysts and
      implanted, but almost all of them aborted spontaneously before embryonic day 7.5.
      CONCLUSIONS: ACS during first mitosis appears to be a major cause of early
      pregnancy losses in ICSI-generated mouse embryos. Moreover, this novel imaging
      technology could be applicable as a method for the assessment of embryo quality.

PMID- 19574277
TI  - Medical treatment for rectovaginal endometriosis: what is the evidence?
AB  - BACKGROUND: Rectovaginal endometriosis usually causes distressing pain. Surgical
      treatment may be effective but is associated with a high risk of morbidity and
      major complications. Information on the effect of medical alternatives for pain
      relief in this condition is scarce. METHODS: A comprehensive literature search
      was conducted to identify all the English language published observational and
      randomized studies evaluating the efficacy of medical treatments on pain
      associated with rectovaginal endometriosis. A combination of keywords was used to
      identify relevant citations in PubMed, MEDLINE and EMBASE. RESULTS: A total of
      217 cases of medically treated rectovaginal endometriosis were found; 68 in five
      observational, non-comparative studies, 59 in one patient preference cohort
      study, and 90 in a randomized controlled trial. An aromatase inhibitor was used
      in two of the non-comparative studies, vaginal danazol in one, a GnRH agonist in
      one, and an intrauterine progestin in one. Two estrogen-progestin combinations
      used transvaginally or transdermally were evaluated in the patient preference
      study, whereas an oral progestin and an estrogen-progestin combination were
      compared in the randomized controlled trial. With the exception of an aromatase
      inhibitor used alone, the antalgic effect of the considered medical therapies was
      high for the entire treatment period (from 6 to 12 months), with 60-90% of
      patients reporting considerable reduction or complete relief from pain symptoms.
      CONCLUSIONS: Despite problems in interpretation of data, the effect of medical
      treatment in terms of pain relief in women with rectovaginal endometriosis appear
      substantial.

PMID- 19574278
TI  - Activation of estrogen receptor-alpha induces gonadotroph progesterone receptor
      expression and action differently in young and middle-aged ovariectomized rats.
AB  - BACKGROUND: We attempted to define the effect of estrogen receptor (ER)alpha
      activation on gonadotroph progesterone receptor (PR) expression (mRNA and
      protein) and action (GnRH-stimulated and GnRH self-priming) in short- and long
      term ovariectomized (OVX) rats. METHODS: Two weeks or 1 year after OVX, rats were
      injected over 3 days with 125 microg/kg of estradiol benzoate (EB), 7.5 mg/kg of
      the selective ERalpha agonist propylpyrazole triol (PPT), or 15 mg/kg of the
      selective ER modulator tamoxifen (TX). Controls were given 0.2 ml oil. The last
      day of ER analog treatment, half of the rats in each group received 25 mg/kg of
      progesterone (P). The next day, anterior pituitaries were removed and analyzed
      for PR-AB mRNA and protein. Gonadotrophin secretion in incubated pituitaries was
      also measured. RESULTS: (i) PR mRNA expression was higher in young than in middle
      aged OVX rats although PR protein was absent in pituitaries from both groups of
      OVX rats; (ii) activation of ERalpha reduced gonadotroph hypertrophy and
      increased PR mRNA and protein expression (EB > PPT > TX) more efficiently in
      young than in middle-aged rats, (iii) ER agonists elicited GnRH-stimulated LH and
      FSH secretion in young but only FSH secretion in middle-aged OVX rats, (iv)
      evaluated by peak LH concentrations, GnRH self-priming was observed in both
      groups of OVX rats and (v) P down-regulated PR protein expression in young, and
      to a lesser extent, in middle-aged OVX rats, in close association with PR
      dependent GnRH self-priming. CONCLUSIONS: Middle-aged OVX rats exhibited clear
      cut LH, but not FSH, secretory defects in pituitary sensitivity to estrogen and
      P.

PMID- 19574279
TI  - Germline VHL gene mutations in Hungarian families with von Hippel-Lindau disease
      and patients with apparently sporadic unilateral pheochromocytomas.
AB  - OBJECTIVE: Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome caused
      by mutations or deletions of the VHL tumor-suppressor gene. Germline VHL gene
      alterations may be also present in patients with apparently sporadic
      pheochromocytoma (ASP), although a wide variation in mutation frequencies has
      been reported in different patient cohorts. DESIGN: Herein, we report the
      analysis of the VHL gene in Hungarian families with VHL disease and in those with
      ASP. METHODS: Seven families (35 members) with VHL disease and 37 unrelated
      patients with unilateral ASP were analyzed. Patients were clinically evaluated
      and the VHL gene was analyzed using direct sequencing, multiplex ligation
      dependent probe amplification, and real-time PCR with SYBR Green chemistry.
      RESULTS: Disease-causing genetic abnormalities were identified in each of the
      seven VHL families and in 3 out of the 37 patients with ASP (one nonsense and six
      missense mutations, two large gene deletions and one novel 2 bp deletion). Large
      gene deletions and other genetic alterations resulting in truncated VHL protein
      were found only in families with VHL type 1, whereas missense mutations were
      associated mainly, although not exclusively, with VHL type 2B and type 2C.
      CONCLUSIONS: The spectrum of VHL gene abnormalities in the Hungarian population
      is similar to that observed in Western, Japanese, or Chinese VHL kindreds. The
      presence of VHL gene mutations in 3 out of the 37 patients with ASP suggests that
      genetic testing is useful not only in patients with VHL disease but also in those
      with ASP.

PMID- 19574280
TI  - Association study of AMP-activated protein kinase subunit genes in polycystic
      ovary syndrome.
AB  - OBJECTIVE: To examine the genes for AMP-activated protein kinase (AMPK) subunits
      alpha2 (PRKAA2) and gamma3 (PRKAG3) as candidates for polycystic ovary syndrome
      (PCOS) and its component traits. DESIGN AND METHODS: A total of 287 white PCOS
      women were recruited from the reproductive endocrinology clinic at the University
      of Alabama at Birmingham and 187 white control subjects were recruited from the
      surrounding community. Seven PRKAA2 single nucleotide polymorphisms (SNPs) and
      four PRKAG3 SNPs were genotyped in PCOS cases and controls. Genotyping and
      association analysis were performed at Cedars-Sinai Medical Center. RESULTS:
      Nominal associations of PRKAA2 variants with insulin-related traits and the
      PRKAG3 Pro71Ala variant with PCOS were not statistically significant after
      multiple testing correction. Among PCOS patients, there were no associations
      between variants in AMPK subunit genes and androgenic or reproductive traits.
      CONCLUSIONS: Variants in genes for AMPKalpha2 and AMPKgamma3 were not associated
      with PCOS or its component traits. Our evidence does not demonstrate that AMPK is
      a major genetic risk factor for PCOS.

PMID- 19574281
TI  - BRAF V600E mutation analysis increases diagnostic accuracy for papillary thyroid
      carcinoma in fine-needle aspiration biopsies.
AB  - OBJECTIVE: Papillary thyroid carcinoma (PTC) represents the majority of
      differentiated thyroid cancers, presenting the V600E activating BRAF mutation in
      29-83% of cases. The aim of our study is to analyze the influence of BRAF
      mutation analysis on the diagnostic accuracy of fine-needle aspiration biopsy
      (FNAB) in patients with suspected PTC. DESIGN AND METHODS: Thyroid cytoaspirates
      from 469 nodules (size: 1.1+/-0.8 cm) with ultrasonographic features suspicious
      of malignant lesion, performed in 374 patients, were submitted to cytological
      evaluation and to biomolecular analysis, carried out after somatic DNA isolation,
      specific PCR amplification, and subsequent automated direct sequencing. All PCR
      fragments were also processed by specific enzyme restriction analysis. RESULTS:
      BRAF V600E mutation was found in 48 samples, 41 of which were also cytologically
      diagnosed as PTC, with histologic confirmation after thyroidectomy. Total
      thyroidectomy was perfomed also in seven patients with negative cytology but
      positive BRAF mutation, with histological confirmation of PTC in all. Among the
      429 BRAF-negative samples, 407 had negative cytology for PTC, while 22 were
      diagnosed as suspected PTC and underwent total thyroidectomy with histological
      diagnosis of PTC in 17 and benign lesion in five. The prevalence of BRAF V600E
      mutation among histologically diagnosed PTC patients was 64%. Biomolecular
      analysis significantly increased cytology sensitivity for PTC from 77.3 to 86.7%
      (P<0.01). CONCLUSIONS: These data indicate that BRAF V600E mutation analysis can
      significantly improve FNAB diagnostic accuracy. However, biomolecular analysis is
      complementary to cytology, which should always be performed.

PMID- 19574282
TI  - The conditional economics of sexual conflict.
AB  - Sexual conflict is a fundamentally important aspect of male-female interactions.
      In this opinion piece, we emphasize two approaches that warrant significantly
      greater attention. First, we review the importance of understanding the
      'economics' (costs and benefits) of sexual interactions and note surprisingly
      large, unrecognized gaps in our knowledge. Second, we highlight the novel
      obstacles and opportunities afforded by the dependence of sexually antagonistic
      (SA) selection on both the local environment and condition of the interacting
      individuals. We conclude that more research in these two areas is essential to
      fully understand the evolution of SA interactions and will provide significant
      new insights into the extent to which coevolution of the sexes is shaped by
      conflict. We argue that these approaches, although not new to the field, are
      undervalued and under-represented.

PMID- 19574283
TI  - Solar activity affects avian timing of reproduction.
AB  - Avian timing of reproduction is strongly affected by ambient temperature. Here we
      show that there is an additional effect of sunspots on laying date, from five
      long-term population studies of great and blue tits (Parus major and Cyanistes
      caeruleus), demonstrating for the first time that solar activity not only has an
      effect on population numbers but that it also affects the timing of animal
      behaviour. This effect is statistically independent of ambient temperature. In
      years with few sunspots, birds initiate laying late while they are often early in
      years with many sunspots. The sunspot effect may be owing to a crucial difference
      between the method of temperature measurements by meteorological stations (in the
      shade) and the temperatures experienced by the birds. A better understanding of
      the impact of all the thermal components of weather on the phenology of
      ecosystems is essential when predicting their responses to climate change.

PMID- 19574284
TI  - SNP-o-matic.
AB  - MOTIVATION: High throughput sequencing technologies generate large amounts of
      short reads. Mapping these to a reference sequence consumes large amounts of
      processing time and memory, and read mapping errors can lead to noisy or
      incorrect alignments. SNP-o-matic is a fast, memory-efficient and stringent read
      mapping tool offering a variety of analytical output functions, with an emphasis
      on genotyping. AVAILABILITY: http://snpomatic.sourceforge.net.

PMID- 19574285
TI  - Unite and conquer: univariate and multivariate approaches for finding
      differentially expressed gene sets.
AB  - MOTIVATION: Recently, many univariate and several multivariate approaches have
      been suggested for testing differential expression of gene sets between different
      phenotypes. However, despite a wealth of literature studying their performance on
      simulated and real biological data, still there is a need to quantify their
      relative performance when they are testing different null hypotheses. RESULTS: In
      this article, we compare the performance of univariate and multivariate tests on
      both simulated and biological data. In the simulation study we demonstrate that
      high correlations equally affect the power of both, univariate as well as
      multivariate tests. In addition, for most of them the power is similarly affected
      by the dimensionality of the gene set and by the percentage of genes in the set,
      for which expression is changing between two phenotypes. The application of
      different test statistics to biological data reveals that three statistics (sum
      of squared t-tests, Hotelling's T(2), N-statistic), testing different null
      hypotheses, find some common but also some complementing differentially expressed
      gene sets under specific settings. This demonstrates that due to complementing
      null hypotheses each test projects on different aspects of the data and for the
      analysis of biological data it is beneficial to use all three tests
      simultaneously instead of focusing exclusively on just one.

PMID- 19574286
TI  - TTA Lynx: a web-based service for analysis of actinomycete genes containing rare
      TTA codon.
AB  - MOTIVATION: TTA Lynx is a web-based service for finding, assessing and comparing
      coding sequences that contain TTA codons. This codon is most notable for being a
      regulatory switch that governs different aspects of the physiology of several GC
      rich, Gram-positive bacteria belonging to genus Streptomyces, prolific producers
      of clinically important natural products. The ever-increasing pace of genome
      sequencing is creating a huge volume of data that could be utilized to improve
      our understanding of rare codons in actinomycete biology (and other biological
      systems.) The service described here is designed to facilitate analysis of TTA
      containing genes and to assess the importance of TTA-mediated regulation in an
      organism of interest. This service and its database of organisms with well-known
      or hypothetical TTA-based regulation provides an opportunity for the
      identification of such regulation on a genome-wide scale. AVAILABILITY:
      http://ttalynx.bio.lnu.edu.ua.

PMID- 19574287
TI  - Statistical lower bounds on protein copy number from fluorescence expression
      images.
AB  - MOTIVATION: Fluorescence imaging has become a commonplace for quantitatively
      measuring mRNA or protein expression in cells and tissues. However, such
      expression data are usually relative-absolute concentrations or molecular copy
      numbers are typically not known. While this is satisfactory for many
      applications, for certain kinds of quantitative network modeling and analysis of
      expression noise, absolute measures of expression are necessary. RESULTS: We
      propose two methods for estimating molecular copy numbers from single
      uncalibrated expression images of tissues. These methods rely on expression
      variability between cells, due either to steady-state fluctuations or unequal
      distribution of molecules during cell division, to make their estimates. We apply
      these methods to 152 protein fluorescence expression images of Drosophila
      melanogaster embryos during early development, generating copy number estimates
      for 14 genes in the segmentation network. We also analyze the effects of noise on
      our estimators and compare with empirical findings. Finally, we confirm an
      observation of Bar-Even et al., made in the much different setting of
      Saccharomyces cerevisiae, that steady-state expression variance tends to scale
      with mean expression. AVAILABILITY: The data are all drawn from FlyEx (explained
      within), and is available at http://flyex.ams.sunysb.edu/FlyEx/.

PMID- 19574288
TI  - Some mechanical aspects of arterial aging: physiological overview based on pulse
      wave analysis.
AB  - Aging has a striking impact on the arterial structure and function. The principal
      structural change with age is medial degeneration that leads to a progressive
      stiffening of the large elastic arteries. Large artery stiffening increases
      aortic systolic and pulse pressures through an increase in the forward incident
      wave and an early return of the backward reflected wave. Peripheral muscular
      arteries/arterioles are only minimally affected in structure by aging itself, but
      impaired vasomotor function can alter their impedance properties and thereby
      increase reflection magnitude. An augmented aortic pressure due to enhanced wave
      reflection increases wasted left ventricular effort and causes cardiac
      hypertrophy. Increased pulsatile pressure and flow stresses extend to the
      vulnerable microcirculation of vasodilated organs such as the brain and kidneys,
      and can predispose to cerebral lacunar infarction and albuminuria. Although most
      currently available vasodilators appear to have little direct effect on
      degenerated elastic arteries, they can act instead on less-degenerated muscular
      arteries to markedly reduce peripheral wave reflection magnitude and central
      aortic pressure, and thus contribute to the regression of left ventricular
      hypertrophy. Further studies are necessary to examine whether the effect of
      vasodilator therapy on reducing wave reflection contributes similarly to the
      prevention of microvascular damage in the brain and kidneys.

PMID- 19574289
TI  - Changes seen in the aging kidney and the effect of blocking the renin-angiotensin
      system.
AB  - BACKGROUND: The objective was to evaluate structural changes of glomeruli during
      aging and the role of chronic renin-angiotensin system inhibition (RASi) on these
      changes; starting RASi on Wistar rats at two different moments: the first group
      after weaning and the second at the midpoint of their lifespan (12 months).
      METHODS: Thirty rats were divided, after weaning, into three groups of 10: group
      1: control (C); group 2 : 30 mg/kg/day losartan (L); group 3 : 10 mg/kg/day
      enalapril (E). At 18 months, rats were placed in metabolic cages to evaluate
      proteinuria, then killed. Another group of 24 rats, 12 months old, were divided
      into three groups of eight: group 1: C; group 2: L; group 3: E. At 18 months the
      same procedure described above was carried out. Finally, a third group of 20 rats
      was studied as healthy controls and killed: 10 rats at 7 months and ten at 12
      months of age. Tissue samples were collected after sacrifice. To evaluate
      glomerular fibrotic changes, both focal and periglomerular sclerosis, and
      mesangial matrix expansion, a scoring scale was established. We also evaluated
      anti-alpha-SM-actin and anti-collagen-III immunolabeling. Glomerular area was
      measured using an image analyzer. RESULTS: Proteinuria and serum creatinine
      increased with age but were reduced in treated animals. Main glomerular changes
      present in 18-month-old rats were reduced by half in treated animals. Glomerular
      area showed significant increase with normal aging and all treatment strategies
      protected against it. CONCLUSION: RAS plays a central role in natural process of
      renal aging, probably by producing effects influencing the biology of aging, the
      effects of which can be attenuated by RASi.

PMID- 19574290
TI  - Only systolic hypertension?

PMID- 19574291
TI  - On the inference of spatial structure from population genetics data.
AB  - MOTIVATION: In a series of recent papers, Tess, a computer program based on the
      concept of hidden Markov random field, has been proposed to infer the number and
      locations of panmictic population units from the genotypes and spatial locations
      of these individuals. The method seems to be of broad appeal as it is
      conceptually much simpler than other competing methods and it has been reported
      by its authors to be fast and accurate. However, this methodology is not grounded
      in a formal statistical inference method and seems to rely to a large extent on
      arbitrary choices regarding the parameters used. The present article is an
      investigation of the accuracy of this method and an attempt to assess whether
      recent results reported on the basis of this method are genuine features of the
      genetic process or artefacts of the method. METHOD: I analyse simulated data
      consisting of populations at Hardy-Weinberg and linkage equilibrium and also data
      simulated under a scenario of isolation-by-distance at mutation-migration-drift
      equilibrium. Arabidopsis thaliana data previously analysed with this method are
      also reconsidered. RESULTS: Using the Tess program under the no-admixture model
      to analyse data consisting of several genuine HWLE populations with individuals
      of pure ancestries leads to highly inaccurate results; Using the Tess program
      under the admixture model to analyse data consisting of a continuous isolation-by
      distance population leads to the inference of spurious HWLE populations whose
      number and features depend on the parameters used. Results previously reported
      about the A.thaliana using Tess seem to a large extent to be artefacts of the
      statistical methodology used. The findings go beyond population clustering models
      and can be an help to design more efficient algorithms based on graphs.
      AVAILABILITY: The data analysed in the present article are available from
      http://folk.uio.no/gillesg/Bioinformatics-HMRF.

PMID- 19574292
TI  - Comment on 'On the inference of spatial structure from population genetics data'.

PMID- 19574293
TI  - The canonical relationship between sensory-motor functioning and cognitive
      processing in children with attention-deficit/hyperactivity disorder.
AB  - Children with Attention-Deficit/Hyperactivity Disorder (ADHD) typically exhibits
      a pattern of behavioral deficits, impairment in academic achievement, and
      cognitive processing, and presents with sensory-motor deficits. This study
      examined the relationships between sensory-motor tasks, cognitive processing, and
      academic achievement for a group of 67 children with ADHD. Strong canonical
      correlations emerged between sensory-motor functioning and academic achievement
      (.93) and sensory-motor functioning and cognitive processing (.98). An analysis
      of the redundancy coefficient showed that sensory-motor skills accounted for 65%
      of the variance in the achievement variables and 31% of the variance in the
      cognitive processing variables. The strong relationship between sensory-motor
      skills and higher order cognitive processes indicates that early assessment of
      sensory-motor skills may be useful in the identification of subsequent deficits
      in academic performance. Neuropsychologists should carefully consider the
      contribution of sensory-motor functioning to the more widely studied and assessed
      constructs of academic, behavioral, and emotional problems in children with ADHD.

PMID- 19574294
TI  - Developing patient registration and medical records management system in
      Ethiopia.
AB  - QUALITY PROBLEM: In low-income countries, medical record management is often
      lacking. We sought to evaluate the impact of an inexpensive business process re
      engineering project on the accessibility and completeness of patient information
      and on physician satisfaction. DESIGN: Pre-post intervention study during 2006
      07, using time-motion studies, medical record audits and physician surveys.
      SETTING: A rural hospital in Ethiopia. PARTICIPANTS: Medical record personnel,
      hospital administrators, clinical staff. IMPLEMENTATION: We implemented a
      hospital-wide patient registration and medical records re-engineering process,
      which included a simple, custom-made computer database to manage patient
      information, standardized medical records forms and processes and enhanced human
      resource management efforts. MAIN OUTCOME MEASURE: s) We measured medical records
      accessibility and completeness, and physician satisfaction. EVALUATION: Medical
      record accessibility and completeness and physician satisfaction improved
      significantly (P < 0.05) based on pre- and post-intervention comparisons. The
      success rate of retrieving the proper medical record number for returning
      patients improved from 14 to 87% (P < 0.01); time to locate medical records
      decreased from 31.2 sec per record to 15.7 sec per record (P < 0.01); the
      percentage of complete medical records increased from 6.5 to 45.7% (P < 0.01).
      Physician satisfaction with the medical records system was significantly higher
      after the intervention (P = 0.02). LESSONS LEARNED: Our findings indicate that a
      well-organized medical record management system can be effective in improving
      patient information accessibility and completeness in hospitals in low-income
      countries despite the lack of resources. Longer follow-up is required to assess
      the sustainability of the hospital improvements accomplished.

PMID- 19574295
TI  - Discovering rules for protein-ligand specificity using support vector inductive
      logic programming.
AB  - Structural genomics initiatives are rapidly generating vast numbers of protein
      structures. Comparative modelling is also capable of producing accurate
      structural models for many protein sequences. However, for many of the known
      structures, functions are not yet determined, and in many modelling tasks, an
      accurate structural model does not necessarily tell us about function. Thus,
      there is a pressing need for high-throughput methods for determining function
      from structure. The spatial arrangement of key amino acids in a folded protein,
      on the surface or buried in clefts, is often the determinants of its biological
      function. A central aim of molecular biology is to understand the relationship
      between such substructures or surfaces and biological function, leading both to
      function prediction and to function design. We present a new general method for
      discovering the features of binding pockets that confer specificity for
      particular ligands. Using a recently developed machine-learning technique which
      couples the rule-discovery approach of inductive logic programming with the
      statistical learning power of support vector machines, we are able to
      discriminate, with high precision (90%) and recall (86%) between pockets that
      bind FAD and those that bind NAD on a large benchmark set given only the geometry
      and composition of the backbone of the binding pocket without the use of docking.
      In addition, we learn rules governing this specificity which can feed into
      protein functional design protocols. An analysis of the rules found suggests that
      key features of the binding pocket may be tied to conformational freedom in the
      ligand. The representation is sufficiently general to be applicable to any
      discriminatory binding problem. All programs and data sets are freely available
      to non-commercial users at http://www.sbg.bio.ic.ac.uk/svilp_ligand/.

PMID- 19574296
TI  - Protein design in biological networks: from manipulating the input to modifying
      the output.
AB  - Protein engineering has been an invaluable tool for the deciphering of protein
      folding and function and in the understanding of biological signaling networks.
      From an applied point of view it has been of paramount importance in
      biotechnological and biopharmaceutical products and applications. Traditionally,
      the protein engineering tools of choice were 'classical' rational design, or
      directed evolution-based methods. In recent years, a third tool has matured:
      computational protein design (CPD). In this review, we summarize the underlying
      principles of CPD and discuss its application for understanding and modifying
      biological systems. Three main applications of the use of protein design will be
      highlighted and reviewed: artificially rewiring of signal transduction networks,
      prediction and generation of large-scale in silico interaction networks and using
      protein design to manipulate gene expression.

PMID- 19574297
TI  - The role of AUF1 in thyroid carcinoma progression.
AB  - AUF1/heterogeneous nuclear ribonucleoprotein D is an adenylate-uridylate-rich
      elements (AREs) -binding protein, which regulates the mRNA stability of many
      genes related to growth regulation, such as proto-oncogenes, growth factors,
      cytokines, and cell cycle-regulatory genes. Several studies demonstrated AUF1
      involvement in the processes of apoptosis, tumorigenesis, and development by its
      interactions with ARE-bearing mRNAs. We report here that AUF1 may be involved in
      thyroid carcinoma progression. Investigations on thyroid tissues revealed that
      cytoplasmic expression of AUF1 in malignant tissues was increased when compared
      with benign thyroid tissues. In thyroid carcinoma cell lines, AUF1 was mostly
      detectable in the nucleus; however, in dividing cells, its increased production
      was also observed in the cytoplasm. We found AUF1 in complexes with ARE-bearing
      mRNAs, previously described to be crucial for proliferation and cell cycle of
      thyroid carcinoma. Total or exon-selective knockdown of AUF1 led to growth
      inhibition accompanied by induction of cell cycle inhibitors and decreased levels
      of cell cycle promoters. Our data demonstrate the existence of a complex network
      between AUF1 and mRNAs encoding proteins related to cell proliferation. AUF1 may
      control the balance between stabilizing and destabilizing effects, both of which
      are exerted on cell cycle machinery in thyroid carcinoma. Although we cannot
      exclude participation of other factors, thyroid carcinoma may recruit cytoplasmic
      AUF1 to disturb the stability of mRNAs encoding cyclin-dependent kinase
      inhibitors, leading to uncontrolled growth and progression of tumor cells. Thus,
      AUF1 may be considered as a new, additional marker for thyroid carcinoma.

PMID- 19574298
TI  - HuR recruits let-7/RISC to repress c-Myc expression.
AB  - RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post
      transcriptional regulators of gene expression. Here, we show that the RBP HuR
      reduced c-Myc expression by associating with the c-Myc 3' untranslated region
      (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved
      the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c
      Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc
      expression and HuR required let-7 to inhibit c-Myc expression. Our findings
      suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting
      let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3'UTR.

PMID- 19574300
TI  - Severe anaemia and subcapital femur fracture in a patient with Left Ventricular
      Assist Device Heart Mate II: the cardiologist's management of this rare patient.
AB  - The use of Left Ventricular Assist Devices (LVADs) has increased over the last
      decade because of the lack of healthy donor hearts. In this report we describe
      for the first time a patient with an LVAD Heart Mate II (HM II) implanted 6
      months before admission, who initially suffered from severe anaemia and later on
      underwent a successful bipolar hip replacement owing to subcapital fracture of
      the right femur. The patient was managed successfully by a team approach, which
      included a cardiologist, anaesthesiologist, orthopaedic surgeon, and LVAD
      technician.

PMID- 19574301
TI  - Biodegradation of phenanthrene by Pseudomonas sp. strain PPD: purification and
      characterization of 1-hydroxy-2-naphthoic acid dioxygenase.
AB  - Pseudomonas sp. strain PPD can metabolize phenanthrene as the sole source of
      carbon and energy via the 'phthalic acid' route. The key enzyme, 1-hydroxy-2
      naphthoic acid dioxygenase (1-HNDO, EC 1.13.11.38), was purified to homogeneity
      using a 3-hydroxy-2-naphthoic acid (3-H2NA)-affinity matrix. The enzyme was a
      homotetramer with a native molecular mass of 160 kDa and subunit molecular mass
      of approximately 39 kDa. It required Fe(II) as the cofactor and was specific for
      1-hydroxy-2-naphthoic acid (1-H2NA), with K(m) 13.5 microM and V(max) 114
      micromol min(-1) mg(-1). 1-HNDO failed to show activity with gentisic acid,
      salicylic acid and other hydroxynaphthoic acids tested. Interestingly, the enzyme
      showed substrate inhibition with a K(i) of 116 microM. 1-HNDO was found to be
      competitively inhibited by 3-H2NA with a K(i) of 24 microM. Based on the pH
      dependent spectral changes, the enzyme reaction product was identified as 2
      carboxybenzalpyruvic acid. Under anaerobic conditions, the enzyme failed to
      convert 1-H2NA to 2-carboxybenzalpyruvic acid. Stoichiometric studies showed the
      incorporation of 1 mol O(2) into the substrate to yield 1 mol product. These
      results suggest that 1-HNDO from Pseudomonas sp. strain PPD is an extradiol-type
      ring-cleaving dioxygenase.

PMID- 19574299
TI  - The axial element protein HTP-3 promotes cohesin loading and meiotic axis
      assembly in C. elegans to implement the meiotic program of chromosome
      segregation.
AB  - Faithful transmission of the genome through sexual reproduction requires
      reduction of genome copy number during meiosis to produce haploid sperm and eggs.
      Meiosis entails steps absent from mitosis to achieve this goal. When meiosis
      begins, sisters are held together by sister chromatid cohesion (SCC), mediated by
      the cohesin complex. Homologs then become linked through crossover recombination.
      SCC subsequently holds both sisters and homologs together. Separation of homologs
      and then sisters requires two successive rounds of chromosome segregation and the
      stepwise removal of Rec8, a meiosis-specific cohesin subunit. We show that HTP-3,
      a known component of the C. elegans axial element (AE), molecularly links these
      meiotic innovations. We identified HTP-3 in a genetic screen for factors
      necessary to maintain SCC until meiosis II. Our data show that interdependent
      loading of HTP-3 and cohesin is a principal step in assembling the meiotic
      chromosomal axis and in establishing SCC. HTP-3 recruits all known AE components
      to meiotic chromosomes and promotes cohesin loading, the first known involvement
      of an AE protein in this process. Furthermore, REC-8 and two paralogs, called COH
      3 and COH-4, together mediate meiotic SCC, but they perform specialized
      functions. REC-8 alone is necessary and sufficient for the persistence of SCC
      after meiosis I. In htp-3 and rec-8 mutants, sister chromatids segregate away
      from one another in meiosis I (equational division), rather than segregating
      randomly, as expected if SCC were completely eliminated. AE assembly fails only
      when REC-8, COH-3, and COH-4 are simultaneously disrupted. Premature equational
      sister separation in rec8 mutants of other organisms suggests the involvement of
      multiple REC-8 paralogs, which may have masked a conserved requirement for
      cohesin in AE assembly.

PMID- 19574303
TI  - Occurrence and characterization of peptaibols from Trichoderma citrinoviride, an
      endophytic fungus of cork oak, using electrospray ionization quadrupole time-of
      flight mass spectrometry.
AB  - A cork oak endophytic strain of Trichoderma citrinoviride, previously selected
      for its antagonistic potential against various fungal pathogens involved in oak
      decline, was screened for the production of bioactive secondary metabolites. From
      liquid culture a mixture of polypeptide antibiotics (peptaibols) belonging to the
      paracelsin family was isolated and characterized. This peptide mixture was
      purified by column chromatography and preparative TLC on silica gel, and
      separated by analytical HPLC. It was analysed by MALDI-TOF MS and nano-ESI-QTOF
      MS. Tandem mass experiments were performed to determine the amino acid sequences
      based on the fragmentation pattern of selected parent ions. The mixture comprised
      20-residue peptides with C-terminal phenylalaninol and N-terminal acetylation.
      Twenty-eight amino acid sequences were identified, and amino acid exchanges were
      located in positions 6, 9, 12 and 17. Among them, seven sequences are new as
      compared to those reported in the database specifically for peptaibols and in the
      literature. In addition, we obtained experimental evidence suggesting the
      existence of non-covalent dimeric forms (homo- and hetero-) of the various
      peptaibol species. The peptide mixture showed strong antifungal activity toward
      seven important forest tree pathogens, and it was highly toxic in an Artemia
      salina (brine shrimp) bioassay. These results emphasize the cryptic role of
      endophytic fungi as a source of novel bioactive natural products and biocontrol
      agents.

PMID- 19574302
TI  - Characterization of the Aspergillus fumigatus phosphomannose isomerase Pmi1 and
      its impact on cell wall synthesis and morphogenesis.
AB  - Phosphomannose isomerase (PMI) is an enzyme catalysing the interconversion of
      mannose 6-phosphate (Man-6-P) and fructose 6-phosphate (Fru-6-P). The reaction
      catalysed by PMI is the first committed step in the synthesis of mannose
      containing sugar chains and provides a link between glucose metabolism and
      mannosylation. In this study, the pmi1 gene was identified to encode PMI in the
      human fungal pathogen Aspergillus fumigatus. Characterization of A. fumigatus
      Pmi1 expressed in Escherichia coli revealed that this PMI mainly catalysed the
      conversion of Fru-6-P to Man-6-P and that its binding affinity for Man-6-P was
      similar to that of yeast PMIs, but different to those of PMIs from bacteria or
      animals. Loss of pmi1 was lethal unless Man was provided in the growth medium.
      However, a Deltapmi1 mutant cell showed a significantly reduced growth rate at a
      high concentration of Man. Biochemical analysis revealed that both inadequate and
      replete Man led to an accumulation of intracellular Man-6-P and a reduction in
      the amount of alpha-glucan in the cell wall. Uncoupling of the link between
      energy production and glycosylation by deletion of the pmi1 gene led to
      phenotypes such as defects in cell wall integrity, abnormal morphology and
      reduced conidiation. Our results reveal that PMI activity is essential for
      viability and plays a central regulatory role in both cell wall synthesis and
      energy production in A. fumigatus.

PMID- 19574304
TI  - Bifidobacterial enolase, a cell surface receptor for human plasminogen involved
      in the interaction with the host.
AB  - The interaction with the host plasminogen/plasmin system represents a novel
      component in the molecular cross-talk between bifidobacteria and human host.
      Here, we demonstrated that the plasminogen-binding bifidobacterial species B.
      longum, B. bifidum, B. breve and B. lactis share the key glycolytic enzyme
      enolase as a surface receptor for human plasminogen. Enolase was visualized on
      the cell surface of the model strain B. lactis BI07. The His-tagged recombinant
      protein showed a high affinity for human plasminogen, with an equilibrium
      dissociation constant in the nanomolar range. By site-directed mutagenesis we
      demonstrated that the interaction between the B. lactis BI07 enolase and human
      plasminogen involves an internal plasminogen-binding site homologous to that of
      pneumococcal enolase. According to our data, the positively charged residues Lys
      251 and Lys-255, as well as the negatively charged Glu-252, of the B. lactis BI07
      enolase are crucial for plasminogen binding. Acting as a human plasminogen
      receptor, the bifidobacterial surface enolase is suggested to play an important
      role in the interaction process with the host.

PMID- 19574305
TI  - Effects of oriC relocation on control of replication initiation in Bacillus
      subtilis.
AB  - In bacteria, DNA replication initiation is tightly regulated in order to
      coordinate chromosome replication with cell growth. In Escherichia coli, positive
      factors and negative regulatory mechanisms playing important roles in the strict
      control of DNA replication initiation have been reported. However, it remains
      unclear how bacterial cells recognize the right time for replication initiation
      during the cell cycle. In the Gram-positive bacterium Bacillus subtilis, much
      less is known about the regulation of replication initiation, specifically,
      regarding negative control mechanisms which ensure replication initiation only
      once per cell cycle. Here we report that replication initiation was greatly
      enhanced in strains that had the origin of replication (oriC) relocated to
      various loci on the chromosome. When oriC was relocated to new loci further than
      250 kb counterclockwise from the native locus, replication initiation became
      asynchronous and earlier than in the wild-type cells. In two oriC-relocated
      strains (oriC at argG or pnbA, 25 degrees or 30 degrees on the 36 degrees
      chromosome map, respectively), DnaA levels were higher than in the wild-type but
      not enough to cause earlier initiation of replication. Our results suggest that
      the initiation capacity of replication is accumulated well before the actual time
      of initiation, and its release may be suppressed by a unique DNA structure formed
      near the native oriC locus.

PMID- 19574306
TI  - Identification of genetic and phenotypic differences associated with prevalent
      and non-prevalent Salmonella Enteritidis phage types: analysis of variation in
      amino acid transport.
AB  - In this study, differences at the genetic level of 37 Salmonella Enteritidis
      strains from five phage types (PTs) were compared using comparative genomic
      hybridization (CGH) to assess differences between PTs. There were approximately
      400 genes that differentiated prevalent (4, 6, 8 and 13a) and sporadic (11) PTs,
      of which 35 were unique to prevalent PTs, including six plasmid-borne genes,
      pefA, B, C, D, srgC and rck, and four chromosomal genes encoding putative amino
      acid transporters. Phenotype array studies also demonstrated that strains from
      prevalent PTs were less susceptible to urea stress and utilized l-histidine, l
      glutamine, l-proline, l-aspartic acid, gly-asn and gly-gln more efficiently than
      PT11 strains. Complementation of a PT11 strain with the transporter genes from
      PT4 resulted in a significant increase in utilization of the amino acids and
      reduced susceptibility to urea stress. In epithelial cell association assays,
      PT11 strains were less invasive than other prevalent PTs. Most strains from
      prevalent PTs were better biofilm formers at 37 degrees C than at 28 degrees C,
      whilst the converse was true for PT11 strains. Collectively, the results indicate
      that genetic and corresponding phenotypic differences exist between strains of
      the prevalent PTs 4, 6, 8 and 13a and non-prevalent PT11 strains that are likely
      to provide a selective advantage for strains from the former PTs and could help
      them to enter the food chain and cause salmonellosis.

PMID- 19574309
TI  - European Commission urges countries to introduce ban on smoking in public places.

PMID- 19574307
TI  - The modular architecture of meningococcal factor H-binding protein.
AB  - Meningococcal factor H binding protein (fHbp) is a promising vaccine antigen that
      binds the human complement downregulatory molecule factor H (fH), and this
      binding enhances the survival of the organism in serum. Based on sequence
      variability of the entire protein, fHbp has been divided into three variant
      groups or two subfamilies. Here, we present evidence based on phylogenetic
      analysis of 70 unique fHbp amino acid sequences that the molecular architecture
      is modular. From sequences of natural chimeras we identified blocks of two to
      five invariant residues that flanked five modular variable segments. Although
      overall, 46 % of the fHbp amino acids were invariant, based on a crystal
      structure, the invariant blocks that flanked the modular variable segments
      clustered on the membrane surface containing the amino-terminal lipid anchor,
      while the remaining invariant residues were located throughout the protein. Each
      of the five modular variable segments could be classified into one of two types,
      designated alpha or beta, based on homology with segments encoded by variant 1 or
      3 fHbp genes, respectively. Forty of the fHbps (57 %) comprised only alpha (n=33)
      or beta (n=7) type segments. The remaining 30 proteins (43 %) were chimeras and
      could be classified into one of four modular groups. These included all 15
      proteins assigned to the previously described variant 2 in subfamily A. The
      modular segments of one chimeric modular group had 96 % amino acid identity with
      those of fHbp orthologs in Neisseria gonorrhoeae. Collectively, the data suggest
      that recombination between Neisseria meningitidis and N. gonorrhoeae progenitors
      generated a family of modular, antigenically diverse meningococcal fHbps.

PMID- 19574308
TI  - Public perceptions, anxiety, and behaviour change in relation to the swine flu
      outbreak: cross sectional telephone survey.
AB  - OBJECTIVE: To assess whether perceptions of the swine flu outbreak predicted
      changes in behaviour among members of the public in England, Scotland, and Wales.
      DESIGN: Cross sectional telephone survey using random digit dialling. SETTING:
      Interviews by telephone between 8 and 12 May. PARTICIPANTS: 997 adults aged 18 or
      more who had heard of swine flu and spoke English. MAIN OUTCOME MEASURES:
      Recommended change in behaviour (increases in handwashing and surface cleaning or
      plans made with a "flu friend") and avoidance behaviours (engaged in one or more
      of six behaviours such as avoiding large crowds or public transport). RESULTS:
      37.8% of participants (n=377) reported performing any recommended behaviour
      change "over the past four days . . . because of swine flu." 4.9% (n=49) had
      carried out any avoidance behaviour. Controlling for personal details and
      anxiety, recommended changes were associated with perceptions that swine flu is
      severe, that the risk of catching it is high risk, that the outbreak will
      continue for a long time, that the authorities can be trusted, that good
      information has been provided, that people can control their risk of catching
      swine flu, and that specific behaviours are effective in reducing the risk. Being
      uncertain about the outbreak and believing that the outbreak had been exaggerated
      were associated with a lower likelihood of change. The strongest predictor of
      behaviour change was ethnicity, with participants from ethnic minority groups
      being more likely to make recommended changes (odds ratio 3.2, 95% confidence
      interval 2.0 to 5.3) and carry out avoidance behaviours (4.1, 2.0 to 8.4).
      CONCLUSIONS: The results support efforts to inform the public about specific
      actions that can reduce the risks from swine flu and to communicate about the
      government's plans and resources. Tackling the perception that the outbreak has
      been "over-hyped" may be difficult but worthwhile. Additional research is
      required into differing reactions to the outbreak among ethnic groups.

PMID- 19574311
TI  - Dementia and marital status at midlife and late life.

PMID- 19574313
TI  - Distribution of insecticide treated nets in rural Africa.

PMID- 19574312
TI  - Association between mid-life marital status and cognitive function in later life:
      population based cohort study.
AB  - OBJECTIVES: To evaluate whether mid-life marital status is related to cognitive
      function in later life. DESIGN: Prospective population based study with an
      average follow-up of 21 years. SETTING: Kuopio and Joensuu regions in eastern
      Finland. PARTICIPANTS: Participants were derived from random, population based
      samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals
      (73%), aged 65-79, underwent re-examination in 1998. MAIN OUTCOME MEASURES:
      Alzheimer's disease and mild cognitive impairment. RESULTS: People cohabiting
      with a partner in mid-life (mean age 50.4) were less likely than all other
      categories (single, separated, or widowed) to show cognitive impairment later in
      life at ages 65-79. Those widowed or divorced in mid-life and still so at follow
      up had three times the risk compared with married or cohabiting people. Those
      widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0)
      for Alzheimer's disease compared with married or cohabiting people. The highest
      increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4
      allele who lost their partner before mid-life and were still widowed or divorced
      at follow-up. The progressive entering of several adjustment variables from mid
      life did not alter these associations. CONCLUSIONS: Living in a relationship with
      a partner might imply cognitive and social challenges that have a protective
      effect against cognitive impairment later in life, consistent with the brain
      reserve hypothesis. The specific increased risk for widowed and divorced people
      compared with single people indicates that other factors are needed to explain
      parts of the results. A sociogenetic disease model might explain the dramatic
      increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.

PMID- 19574314
TI  - Addison's disease.

PMID- 19574315
TI  - Addison's disease.

PMID- 19574317
TI  - Measuring patients' experiences and outcomes.

PMID- 19574318
TI  - Heat waves and dehydration in the elderly.

PMID- 19574321
TI  - The metabolic syndrome in older persons: a loosely defined constellation of
      symptoms or a distinct entity?

PMID- 19574316
TI  - Household ownership and use of insecticide treated nets among target groups after
      implementation of a national voucher programme in the United Republic of
      Tanzania: plausibility study using three annual cross sectional household
      surveys.
AB  - OBJECTIVES: To evaluate the impact of the Tanzania National Voucher Scheme on the
      coverage and equitable distribution of insecticide treated nets, used to prevent
      malaria, to pregnant women and their infants. DESIGN: Plausibility study using
      three nationally representative cross sectional household and health facility
      surveys, timed to take place early, mid-way, and at the end of the roll out of
      the national programme. SETTING: The Tanzania National Voucher Scheme was
      implemented in antenatal services, and phased in on a district by district basis
      from October 2004 covering all of mainland Tanzania in May 2006. PARTICIPANTS:
      6115, 6260, and 6198 households (in 2005, 2006, and 2007, respectively) in a
      representative sample of 21 districts (out of a total of 113). INTERVENTIONS: A
      voucher worth $2.45 ( pound1.47, euro1.74) to be used as part payment for the
      purchase of a net from a local shop was given to every pregnant woman attending
      antenatal services. MAIN OUTCOME MEASURES: Insecticide treated net coverage was
      measured as household ownership of at least one net and use of a net the night
      before the survey. Socioeconomic distribution of nets was examined using an asset
      based index. RESULTS: Steady increases in net coverage indicators were observed
      over the three year study period. Between 2005 and 2007, household ownership of
      at least one net (untreated or insecticide treated) increased from 44%
      (2686/6115) to 65% (4006/6198; P<0.001), and ownership of at least one
      insecticide treated net doubled from 18% (1062/5961) to 36% (2229/6198) in the
      same period (P<0.001). Among infants under 1 year of age, use of any net
      increased from 33% (388/1180) to 56% (707/1272; P<0.001) and use of an
      insecticide treated net increased from 16% (188/1180) to 34% (436/1272; P<0.001).
      After adjusting for potential confounders, household ownership was positively
      associated with time since programme launch, although this association did not
      reach statistical significance (P=0.09). Each extra year of programme operation
      was associated with a 9 percentage point increase in household insecticide
      treated net ownership (95% confidence interval -1.6 to 20). In 2005, only 7%
      (78/1115) of nets in households with a child under 1 year of age had been
      purchased with a voucher; this value increased to 50% (608/1211) in 2007
      (P<0.001). In 2007, infants under 1 year in the least poor quintile were more
      than three times more likely to have used an insecticide treated net than infants
      in the poorest quintile (54% v 16%; P<0.001). CONCLUSIONS: The Tanzania National
      Voucher Scheme was associated with impressive increases in the coverage of
      insecticide treated nets over a two year period. Gaps in coverage remain,
      however, especially in the poorest groups. A voucher system that facilitates
      routine delivery of insecticide treated nets is a feasible option to "keep up"
      coverage.

PMID- 19574322
TI  - The effect on caregiver burden of a problem-based home visiting programme for
      frail older people.
AB  - OBJECTIVE: caregiver effects of geriatric care models focusing primarily at the
      patient have not been consistently studied. We studied caregiver effects of a
      nurse-led comprehensive geriatric evaluation and management (GEM) programme for
      community-dwelling frail older people that showed-in a randomised comparison with
      usual care--health-related quality of life benefits for the care receivers.
      METHODS: this randomised trial included 110 caregiver/patient dyads who were
      followed up for 6 months. Primary analyses were intention-to-treat analyses of
      caregiver burden assessed with Zarit Burden Interview (ZBI; 0-88; higher means
      more burden). Preplanned subgroup analyses were conducted for cognition, living
      arrangement and patient/caregiver co-residence. RESULTS: overall, perceived
      caregiver burden showed no significant differences between study groups in
      changes over time. However, perceived burden was at baseline more than eight
      points higher in caregivers sharing a household with patients (n = 23) compared
      to caregivers living separately (n = 87). The intervention performed better in
      caregivers living together with the patient than in caregivers living separately
      (P for interaction = 0.04). Co-resident caregivers experienced six-Zarit point
      improvement compared with four-point deterioration in the non-co-resident
      caregivers. CONCLUSIONS: GEM at home benefited patients, but maybe not
      caregivers. Caregiver effects are related to whether caregivers live with the
      patient or not.

PMID- 19574323
TI  - CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and
      hypoxaemic COPD.
AB  - Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic
      obstructive pulmonary disease (COPD). The present prospective cohort study tested
      the effect of OSAS treatment with continuous positive airway pressure (CPAP) on
      the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment
      would be associated with higher survival in patients with moderate-to-severe OSAS
      and hypoxaemic COPD receiving long-term oxygen therapy (LTOT). Prospective study
      participants attended two outpatient advanced lung disease LTOT clinics in Sao
      Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD
      patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this
      OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and
      34 did not accept or were not adherent and were considered not treated. The 5-yr
      survival estimate was 71% (95% confidence interval 53-83%) and 26% (12-43%) in
      the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting
      for several confounders, patients treated with CPAP showed a significantly lower
      risk of death (hazard ratio of death versus nontreated 0.19 (0.08-0.48)). The
      present study found that CPAP treatment was associated with higher survival in
      patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.

PMID- 19574324
TI  - Bleomycin induces pleural and subpleural fibrosis in the presence of carbon
      particles.
AB  - The pathological changes in idiopathic pulmonary fibrosis (IPF) typically start
      in subpleural lung regions, a feature that is currently not explained. IPF, as
      well as bleomycin-induced lung fibrosis, are more common in smokers. We
      hypothesised that carbon particles, which are major components of cigarette smoke
      that are transported to alveoli and pleural surface, might be involved in the
      development of subpleural fibrosis through interaction with pleural mesothelial
      cells. Carbon particles were administered to mice in combination with bleomycin
      through intratracheal and/or intrapleural injection and fibrosis was assessed
      using histomorphometry. Carbon administered to the chest cavity caused severe
      pleural fibrosis in the presence of bleomycin, whereas bleomycin alone had no
      fibrogenic effect. The pleural response was associated with progressive fibrosis
      in subpleural regions, similar to IPF in humans. Matrix accumulation within this
      area evolved through mesothelial-fibroblastoid transformation, where mesothelial
      cells acquire myofibroblast characteristics. In contrast, carbon did not
      exaggerate bleomycin-induced pulmonary fibrosis after combined intratracheal
      administration. This represents a novel approach to induce a robust experimental
      model of pleural fibrosis. It also suggests that carbon particles might be
      involved as a cofactor in the initiation and/or progression of (subpleural)
      pulmonary and pleural fibrosis. Mesothelial cells appear to be critical
      contributors to this fibrotic process.

PMID- 19574326
TI  - Prevalence and severity of self-reported asthma in young adults, 1976-2004.
AB  - The aim of the present study was to describe the prevalence and severity of
      asthma in young Danish adults over three decades. Males and females aged 20-35
      yrs were sampled from the population of Copenhagen for the three surveys (1976
      1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male) subjects answered a
      questionnaire, and had their height, weight, forced expiratory volume in 1 s
      (FEV1) and forced vital capacity measured. The prevalence of self-reported asthma
      was 1.5, 4.7 and 6.9%, respectively, in the three surveys (p<0.001). An
      increasing prevalence of asthma was observed in both males and females, although
      it was highest among females. The difference in FEV1 between asthmatic and
      nonasthmatic subjects gradually increased, being 2.3 (p = 0.56) and 14.2% of the
      predicted value (p<0.001), respectively, in 1976-1978 and 2001-2004. From the
      1991-1994 survey, increasing body mass index, especially >30 kg.m(-2), was
      associated with a lower percentage predicted FEV1 (p< or =0.005), and further
      analyses suggested an additive effect of asthma and obesity on FEV1. The
      proportion of smokers declined from 60 to 38% (p<0.001). The prevalence and
      severity of asthma have continued to increase over the last three decades among
      young Danish adults, and the observed increase in severity seems, at least
      partly, to be related to the increase in prevalence of obesity.

PMID- 19574325
TI  - Control of breathing in children with mild sleep apnoea: a 6-year follow-up
      study.
AB  - We have previously shown that children (average age 9 yrs) with mildly elevated
      obstructive apnoea/hypopnoea indices (OAHI) retained CO(2) at rest. Here, we
      report the results of a 6-yr follow-up study on 14 children from that study.
      Minute ventilation (V'(E)) and end-tidal CO(2) partial pressure (P(ET,CO(2)))
      were measured during hypercapnic challenge. OAHI decreased from 7.5+/-4.7 events
      x h(-1) at age 9 yrs to 2.5+/-1.8 events x h(-1) at age 15 yrs (p<0.001), despite
      an increase in body mass index from 20+/-4.6 kg x m(-2) to 26+/-5.7 kg x m(-2)
      (p<0.0001). Eupneic V'(E) increased from 4.1+/-0.31 L x min(-1) x m(-2) to 5.9+/
      0.4 L x min(-1) x m(-2) (p<0.01), while P(ET,CO(2)) fell from 44.1+/-0.8 to 33+/
      1.0 mmHg (p<0.001). The V'(E)-P(ET,CO(2)) obtained during hypercapnia was left
      shifted, such that V'(E) at a P(ET,CO(2)) of 50 mmHg increased from 24 L x min(
      1) at age 9 yrs to 36 L x min(-1) at age 15 yrs. Central respiratory drive did
      not change. We hypothesise that somatic growth of the pharynx coupled with a
      regression of tonsillar tissue mass with age leads to enlargement of the upper
      airway lumen, a reduction in airway resistance and increased respiratory airflow
      at a given level of ventilatory drive.

PMID- 19574328
TI  - Quality of randomised trials in COPD.
AB  - Randomised trials can provide high-level evidence to inform treatment decisions.
      Since their quality in respiratory medicine is largely unknown, we assessed the
      quality of a large set of chronic obstructive pulmonary disease (COPD) trials. As
      a marker of trial quality, we assessed the procedure and concealment of random
      allocation, and the conduct of an intention-to-treat-analysis in 344 randomised
      trials published between 1957 and 2006. We used ordered logistic regression to
      assess the association between trial quality and type of intervention, type of
      journal, journal impact factor and year of publication. 257 (75%) trials assessed
      pharmacological and 87 (25%) assessed nonpharmacological interventions. The
      generation of appropriate randomisation was reported in 27.0% of the trials,
      concealment of random allocation in 11.6% and an intention-to-treat analysis in
      21.8% of trials. Significantly higher quality was found in trials on
      nonpharmacological interventions (OR 2.49, 95% CI 1.56-3.99), and in trials
      published in general medical journals (versus specialised journals; OR 2.25, 95%
      CI 1.30-3.90) and after 2000 (versus 1957-2000; OR 2.28, 95% CI 1.45-3.58). The
      association of quality with a high impact factor was of borderline significance
      (p = 0.06). The quality of many COPD trials is low but tends to become better
      since the adoption of the CONSORT (Consolidated Standards of Reporting Trials)
      statement.

PMID- 19574327
TI  - Bronchial nitric oxide is related to symptom relief during fluticasone treatment
      in COPD.
AB  - High levels of exhaled nitric oxide (NO) predict favourable response to inhaled
      corticosteroids in asthma, but the ability of exhaled NO or inflammatory markers
      in exhaled breath condensate (EBC) to predict steroid responsiveness in chronic
      obstructive pulmonary disease (COPD) is not known. We measured alveolar and
      bronchial NO output, levels of leukotriene B(4) (LTB(4)), cysteinyl leukotrienes
      (cysLTs) and 8-isoprostane in EBC, spirometry, body plethysmography and symptoms
      in 40 subjects with COPD before and after 4 weeks of treatment with inhaled
      fluticasone (500 microg b.i.d.). Five subjects (12.5%) with COPD had significant
      improvement in lung function during fluticasone treatment, whereas 20 subjects
      (50%) had significant decrease in symptoms. High baseline bronchial NO flux was
      associated with higher increase in forced expiratory volume in 1 s to forced
      vital capacity ratio (r = 0.334, p = 0.038) and more symptom relief (r = -0.317,
      p = 0.049) during the treatment. Baseline EBC levels of LTB(4), cysLTs or 8
      isoprostane were not related to response to fluticasone treatment. Inhaled
      fluticasone decreased bronchial NO flux but not alveolar NO concentration or
      markers in EBC. High levels of bronchial NO flux are related to symptom relief
      and improvement of airway obstruction during treatment with inhaled fluticasone
      in COPD. Markers of inflammation or oxidative stress in EBC are not related to
      steroid responsiveness in COPD.

PMID- 19574329
TI  - Interleukin-8 activates coagulation and correlates with survival after talc
      pleurodesis.
AB  - The aim of our study was to investigate whether interleukin (IL)-8 activates
      systemic coagulation after talc pleurodesis in malignant pleural effusion (MPE),
      and whether levels of IL-8 in plasma are related to early death after talc
      pleurodesis. IL-8 and tumour necrosis factor (TNF)-alpha were measured in samples
      from 231 MPE patients before and after talc pleurodesis. Whole blood from 31
      healthy volunteers was incubated with IL-8, TNF-alpha and thromboplastin for 3 h
      in vitro, and thrombin-antithrombin (TAT) levels were measured. The same
      stimulation of blood samples was repeated using doses of calibrated talc. Nine,
      12 and 17 patients died within 7, 10 and 15 days respectively. IL-8 was elevated
      in 102 patients within 48 h, and thrombotic events were observed in six of those
      patients. Survival correlated inversely with IL-8 at 24 and 48 h, and a
      significant correlation was also found between IL-8 and TAT. A positive dose
      dependent correlation with TAT production was observed when blood was stimulated
      with IL-8 in vitro. However, there was no significant response to stimulation
      with talc, as compared with control blood samples. IL-8 is involved in the
      activation of coagulation that may occur after talc pleurodesis, and might also
      be implicated in early death of patients with MPE.

PMID- 19574330
TI  - Long-term time-course of nocturnal breathing disorders in heart failure patients.
AB  - Some important aspects of clinical manifestations of nocturnal breathing
      disorders in heart failure (HF) patients are still unknown. We questioned whether
      the severity of these disorders, first, is stable over time; secondly, shows any
      systematic trend; and, thirdly, can be predicted over time by a single baseline
      measurement. We studied 79 stable, optimally treated, moderate-to-severe HF
      patients who performed a monthly cardiorespiratory recording during 1-yr follow
      up. According to their behaviour over time, nocturnal breathing disorders were
      classified as persistent, absent or occasional. During follow-up, clinically
      relevant breathing disorders were persistent in approximately 50% of the
      patients, absent in <20% and occasional in approximately 30%.
      Increasing/decreasing trends were rarely observed. The positive and negative
      predictive value of baseline measurement for persistent behaviour over time
      ranged, respectively, from 71% to 91% and from 91% to 95%, depending on different
      levels of severity of breathing disorders. A large portion of HF patients
      experience persistent clinically significant nocturnal breathing disorders over
      long periods of time. Breathing disorders occur irregularly in about one-third of
      the patients and are negligible in a minority of them. Rarely do they show a
      steady increase or decrease over time. A single baseline recording predicts a
      persistent behaviour with moderate-to-high accuracy.

PMID- 19574331
TI  - Is INTERdisciplinary COMmunity-based COPD management (INTERCOM) cost-effective?
AB  - The study aimed to estimate the cost-effectiveness of interdisciplinary community
      based chronic obstructive pulmonary disease (COPD) management in patients with
      COPD. We conducted a cost-effectiveness analysis alongside a 2-yr randomised
      controlled trial, in which 199 patients with less advanced airflow obstruction
      and impaired exercise capacity were assigned to the INTERCOM programme or usual
      care. The INTERCOM programme consisted of exercise training, education,
      nutritional therapy and smoking cessation counselling offered by community-based
      physiotherapists and dieticians and hospital-based respiratory nurses. All-cause
      resource use during 2 yrs was obtained by self-report and from hospital and
      pharmacy records. Health outcomes were the St George's Respiratory Questionnaire
      (SGRQ), exacerbations and quality-adjusted life years (QALYs). The INTERCOM group
      had 30% (95% CI 3-56%) more patients with a clinically relevant improvement in
      SGRQ total score, 0.08 (95% CI -0.01-0.18) more QALYs per patient, but a higher
      mean number of exacerbations, 0.84 (95% CI -0.07-1.78). Mean total 2-yr costs
      were euro2,751 (95% CI -euro632-euro6,372) higher for INTERCOM than for usual
      care, which resulted in an incremental cost-effectiveness ratio of euro9,078 per
      additional patient with a relevant improvement in SGRQ or euro32,425 per QALY.
      INTERCOM significantly improved disease-specific quality of life, but did not
      affect exacerbation rate. The cost per QALY ratio was moderate, but within the
      range of that generally considered to be acceptable.

PMID- 19574332
TI  - Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study.
AB  - There is some evidence that chronic obstructive pulmonary disease (COPD) and
      metabolic syndrome may be related, perhaps through systemic inflammation, which
      is common to both. However, the association between the two conditions has not
      yet been clearly shown. The present study involved 7,358 adults aged > or =50 yrs
      from a population-based survey who underwent spirometry, a structured interview
      and measurement of fasting metabolic marker levels. Airflow obstruction (forced
      expiratory volume in 1 s/forced vital capacity ratio of less than the lower limit
      of normal) was present in 6.7%, and the International Diabetes Federation
      metabolic syndrome criteria were met by 20.0%. The risk of metabolic syndrome was
      higher in those with airflow obstruction than in those without (odds ratio (OR)
      1.47; 95% confidence interval (CI) 1.12-1.92), after controlling for potential
      confounders. Of the five components of metabolic syndrome, only central obesity
      was significantly associated with airflow obstruction (OR 1.43; 95% CI 1.09-1.88)
      after adjusting for body mass index. A similar association was observed in both
      never and current smokers. In this Chinese sample, airflow obstruction was
      associated with metabolic syndrome, and, in particular, its central obesity
      component. This may help explain the increased risk of cardiovascular diseases in
      COPD, and so could guide future clinical practice.

PMID- 19574333
TI  - Interaction of T-cell and antigen presenting cell co-stimulatory genes in
      childhood IgE.
AB  - It is likely that multiple genes contribute to immunoglobulin (Ig)E production.
      Co-stimulatory molecules are crucial for the cross-talk between antigen
      presenting cells and T-lymphocytes which drives the IgE response. We evaluated
      gene-gene interactions of haplotype tagging polymorphisms in a pathway of 24 co
      stimulatory genes in relation to serum IgE levels. We assessed this at ages 1-2
      yrs and 6-8 yrs in 3,062 Dutch children from a pooled data set of three birth
      cohorts: PIAMA (Prevention and Incidence Asthma and Mite Allergy), PREVASC
      (Prevention of Asthma in Children) and KOALA (Child, parents and health:
      lifestyle and genetic constitution). Single- and multi-locus associations with
      serum IgE levels (3rd versus 1st tertile) were evaluated by Chi-squared tests and
      the multifactor dimensionality reduction (MDR) method in the following co
      stimulatory genes: VTCN1, TNFRSF4, TNFRSF18, TNFRSF14, TNFSF18, TNFSF4, CD28,
      CTLA4, ICOS, PDCD1, BTLA, CD80, CD86, HLA-G, CD274, PDCD1LG2, CD276, LILRA4,
      LILRB1, LILRB2, LILRB4, CD40, ICOSLG, and CD40LG. We found multiple statistically
      significant single-locus ((S)) and multi-locus ((M)) associations for the genes
      VTCN1(SM), TNFSF18(SM), TNFSF4(S), CD28(S), CTLA4(M), ICOS(S), BTLA(M), CD80(M),
      CD86(SM), CD274(SM), PDCD1LG2(M), LILRA4(SM), LILRB4(M), and CD40(SM) with serum
      IgE. Two-locus interactions of CD86 with VTCN1 and CD274 with LILRA4 were
      confirmed by logistic regression. In conclusion, serum IgE levels are regulated
      by multiple gene-gene interaction effects in the co-stimulatory pathway. We
      suggest using research strategies that model multiple gene-gene interactions in
      genetic studies.

PMID- 19574335
TI  - Effect of sleeping alone on sleep quality in female bed partners of snorers.
AB  - The aim of the present study was to objectively measure the effect of sleeping
      alone for one night on sleep quality in female bed partners of male snorers.
      Females complaining of poor sleep due to snoring by their bed partner and having
      no known hearing loss or snoring were included in a prospective multicentre cross
      sectional study. 23 females underwent one polysomnography recording while
      sleeping with their bed partner and another while sleeping alone. Their sleep
      parameters were compared between the two nights. We excluded seven couples
      because the female partner snored for >10% of the sleep time (n = 6) or had
      obstructive sleep apnoea syndrome (n = 1). In the remaining 16 females, sleep
      time, sleep efficiency, arousal index and percentages of deep sleep (stages 3-4)
      and rapid eye movement (REM) sleep were not significantly different between the
      two nights. Percentages of light sleep (non-REM stage 2) and awakening index were
      lower when sleeping alone (p = 0.023 and p = 0.046, respectively). Sleep quality
      was decreased and sleep fragmentation increased in females sleeping with male
      snorers. Some females had unrecognised snoring. However, our data do not suggest
      that objective sleep quality improves substantially in the female nonsnoring
      partner when she sleeps alone for one night.

PMID- 19574334
TI  - Transcutaneous carbon dioxide profile during sleep reveals metabolic risk factors
      in post-menopausal females.
AB  - The risks of metabolic syndrome and sleep-disordered breathing increase around
      the time of the menopause. We have previously shown that features of the
      nocturnal transcutaneous carbon dioxide (TcCO2) profile are associated with
      metabolic variables such as cholesterol, glycosylated haemoglobin A1C (GHbA1C)
      and blood pressure in patients with sleep apnoea. In the present study, we
      investigated whether these metabolic variables can be predicted using noninvasive
      TcCO2 measurements during sleep in generally healthy post-menopausal females. 22
      post-menopausal females underwent an overnight polygraphic sleep study that
      involved the continuous monitoring of arterial oxygen saturation (S(a,O2)) and
      TcCO2. Body composition, GHbA1C, plasma cholesterol and blood pressure were
      measured prior to the sleep study. Nocturnal TcCO2 features were the most
      important predictors of lipoprotein cholesterols, triglycerides and blood
      pressure levels. A longer sleep period and higher TcCO2 levels were linked with
      lower GHbA1C, and fragmented sleep with lower high-density lipoprotein
      cholesterol. Neither nocturnal S(a,O2) indices nor the apnoea/hypopnoea index had
      a predictive power. The results suggest that nocturnal TcCO2 events revealed
      metabolic risk factors already present in healthy post-menopausal females.

PMID- 19574336
TI  - Pathogenic role of angiotensin II and oxidised LDL in obstructive sleep apnoea.
AB  - A sustained elevation of oxidative stress in patients with obstructive sleep
      apnoea syndrome (OSAS) might help to explain their increased risk for
      cardiovascular diseases. We tested the hypothesis that the values of oxidative
      stress are increased in otherwise healthy subjects with OSAS when compared with
      closely matched control subjects. We performed a prospective study of 38 subjects
      who did not have OSAS and 37 patients with OSAS. Plasma indices of angiotensin
      (Ang) II, vascular endothelial growth factor (VEGF), oxidised low-density
      lipoprotein (oxLDL), and circulating endothelial precursor cells (CEPs) were
      measured in OSAS patients and in matched controls. Peripheral blood mononuclear
      cells (PBMCs) were obtained from both groups and co-cultured with endothelial
      cells to examine the effects on tube formation. The OSAS group showed increased
      levels of Ang II, VEGF, oxLDL and CEPs, which were decreased after nasal
      continuous positive airway pressure (nCPAP) treatment. In vitro, PBMCs from the
      OSAS group induced tube formation. Ang II, oxLDL, and Ang II-stimulated PBMCs
      induced lectin-like oxLDL receptor (LOX-1) expression and VEGF receptor-2
      activation on endothelial cells, respectively. These observations suggest an
      important role of Ang II and oxLDL-mediated LOX-1 upregulation in endothelial
      cell injury in patients with OSAS.

PMID- 19574337
TI  - Long-term mortality and cardiovascular risk stratification of peritoneal dialysis
      patients using a combination of inflammation and calcification markers.
AB  - BACKGROUND: It remains unknown whether a composite of inflammation and
      calcification markers provides better mortality and cardiovascular risk
      stratification in chronic peritoneal dialysis (PD) patients. METHODS: We
      performed a 4-year prospective follow-up study in 231 chronic PD patients from a
      single regional dialysis centre in Hong Kong. Valvular calcification was detected
      using echocardiography, and fasting venous blood was collected to measure a panel
      of inflammation markers. The patients were stratified into five groups on the
      basis of 0, 1, 2, 3 and all 4 inflammation and calcification risk markers, namely
      high C-reactive protein (CRP) (CRP in upper tertile), high interleukin-6 (IL-6)
      (IL-6 in upper tertile), low fetuin-A (fetuin-A in lower tertile) and valvular
      calcification. Study outcomes included all-cause and cardiovascular mortality and
      fatal or non-fatal cardiovascular events (CVEs). RESULTS: The patients with 4, 3,
      2 and 1 markers had an adjusted hazard ratio (HR) of 5.17 (95% CI, 1.81-14.77, P
      = 0.002), 3.38 (95% CI, 1.50-7.60; P = 0.003), 2.17 (95% CI, 0.98-4.77; P =
      0.056) and 2.42 (95% CI, 1.18-4.96; P = 0.016), respectively, for mortality at 4
      years than those with 0 risk marker. The adjusted HRs for fatal or non-fatal CVEs
      were 4.33 (95% CI, 1.70-11.03; P = 0.002), 1.60 (95% CI, 0.73-3.52; P = 0.24),
      1.92 (95% CI, 0.95-3.90; P = 0.07) and 1.33 (95% CI, 0.67-2.62; P = 0.42),
      respectively, for patients with 4, 3, 2 and 1 markers than those with 0 risk
      markers. CONCLUSIONS: A composite of inflammation and calcification markers
      provides long-term prognostication and identifies the sickest PD patients with
      the worst clinical outcomes. Since these parameters can all be obtained quite
      readily, our data support the adoption of a multiinflammation and calcification
      risk marker approach for mortality and cardiovascular risk stratification in PD
      patients.

PMID- 19574338
TI  - As nature did not predict dialysis--what we can learn from FGF23 in end-stage
      renal disease?

PMID- 19574339
TI  - Corynebacterium peritonitis in Australian peritoneal dialysis patients:
      predictors, treatment and outcomes in 82 cases.
AB  - BACKGROUND: Infection due to Corynebacterium species has been reported with
      increasing frequency over recent decades. The impacts of enhanced laboratory
      detection together with widespread use of new peritoneal dialysis (PD) connection
      technology and antimicrobial prophylaxis strategies on Corynebacterium PD
      associated peritonitis have not been well studied. METHODS: We investigated the
      frequency, predictors, treatment and clinical outcomes of Corynebacterium
      peritonitis in all Australian adult patients involving 66 centres who were
      receiving PD between 1 October 2003 and 31 December 2006. RESULTS: Eighty-two
      episodes of Corynebacterium peritonitis (2.3% of all peritonitis episodes)
      occurred in 65 (1.4%) PD patients. Ten (15%) patients experienced more than one
      episode of Corynebacterium peritonitis and additional organisms were isolated in
      12 (15%) episodes of Corynebacterium peritonitis. The incidence of
      Corynebacterium peritonitis was significantly and independently predicted only by
      BMI: RR 2.72 (95% CI 1.38-5.36) for the highest tertile BMI compared with the
      lowest tertile. The overall cure rate with antibiotics alone was 67%, which was
      similar to that of peritonitis due to other organisms. Vancomycin was the most
      common antimicrobial agent administered in the initial empiric and subsequent
      antibiotic regimens, although outcomes were similar regardless of antimicrobial
      schedule. Corynebacterium peritonitis not infrequently resulted in relapse (18%),
      repeat peritonitis (15%), hospitalization (70%), catheter removal (21%),
      permanent haemodialysis transfer (15%) and death (2%). The individuals who had
      their catheters removed more than 1 week after the onset of Corynebacterium
      peritonitis had a significantly higher risk of permanent haemodialysis transfer
      than those who had their catheters removed within 1 week (90% versus 43%, P <
      0.05). CONCLUSIONS: Corynebacterium is an uncommon but significant cause of PD
      associated peritonitis. Complete cure with antibiotics alone is possible in the
      majority of patients, and rates of adverse outcomes are comparable to those seen
      with peritonitis due to other organisms. Use of vancomycin rather than cephazolin
      as empiric therapy does not impact outcomes, and a 2-week course of antibiotic
      therapy appears sufficient. If catheter removal is required, outcomes are
      improved by removing the catheter within 1 week of peritonitis onset.

PMID- 19574340
TI  - Post-menopausal hormone use and albuminuria.
AB  - BACKGROUND: Higher levels of urinary albumin excretion predict future
      hypertension and chronic kidney disease. Post-menopausal hormone use may
      influence the renin-angiotensin system and renal endothelial function, impacting
      albumin excretion. The association between post-menopausal hormone use and
      albuminuria is not well defined. METHODS: We explored the cross-sectional
      association between duration of PMH use and albuminuria in 2445 post-menopausal,
      non-diabetic women from the Nurses' Health Study. Women were categorized as
      hormone non-users, past users or current users grouped by 3-year intervals of
      duration of use, from < or =3 years to >15 years. The outcome was the top decile
      of urine albumin/creatinine ratio (ACR). Multivariate logistic regression was
      used to assess the association between duration of PMH use and risk of being in
      the top decile. RESULTS: The mean age was 66.8 years, and 57% were currently
      using PMH. The median ACR was 2.9 mg/g, and the 90th percentile was 9.2 mg/g.
      Compared with women with no history of PMH use, the odds ratio for being in the
      top ACR decile was lower for women with use of >6-9 years, >9-12 years, >12-15
      years and >15 years, but there was no dose-response. The overall odds ratio was
      0.55 (95% CI: 0.39-0.77) among women with >6 years of current PMH use compared
      with non-users. Current hormone use of shorter duration and past hormone use were
      not associated with albumin excretion. CONCLUSIONS: Current PMH use of >6 years
      is associated with a lower urinary ACR in non-diabetic women.

PMID- 19574341
TI  - RAS meets SLE.

PMID- 19574342
TI  - A cut-off value of plasma osteoprotegerin level may predict the presence of
      coronary artery calcifications in chronic kidney disease patients.
AB  - BACKGROUND: Expression of bone proteins resulting from transdifferentiation of
      vascular smooth muscle cells into osteoblasts suggests that vascular
      calcifications are a bioactive process. Osteoprotegerin (OPG) could play a key
      role in bone-vascular calcification imbalance and could be a marker of vascular
      calcification extent and progression. The purpose of this study was to evaluate
      relationships between vascular risk biomarkers (including classic risk factors
      and OPG) and coronary artery calcification (CAC) extent in chronic kidney disease
      (CKD) patients and to establish within the markers the appropriate cut-off value
      to predict CAC. METHODS: A total of 133 non-dialyzed CKD patients at various
      stages of kidney disease [75 males/58 females, median age: 69.9 (27.4-94.6)] were
      enrolled, excluding extrarenal replacement therapy patients. All underwent chest
      multidetector computed tomography for CAC scoring. Blood samples were collected
      for measurement of vascular risk markers (kidney disease, inflammation,
      nutrition, calcium phosphate and OPG). A potential relationship between CAC and
      these biological markers was investigated, and a receiver-operating
      characteristic (ROC) curve was designed thereafter to identify a cut-off value of
      involved markers that best predicted the presence of CAC. RESULTS: After
      adjustment for age, diabetes, smoking and gender, among biological markers, only
      low-estimated glomerular filtration rate using Modification of Diet in Renal
      Disease [OR = 3.63 (1.10-12.02)], high FEPO(4) [OR = 3.99 (1.17-13.6)] and high
      OPG levels [OR = 8.54 (2.14-34.11)] were associated with the presence of CAC. A
      protective effect of 1.25(OH)(2) vitamin D [OR = 0.20 (0.05-0.79)] and LDL
      cholesterol [OR = 0.27 (0.08-0.94)] on CAC was also observed. ROC curve analysis
      showed that the OPG best cut-off value predicting CAC was 757.7 pg/mL.
      CONCLUSION: These results suggest that a CAC increase is strongly associated with
      a plasma OPG increase in CKD patients. The values of OPG >757.7 pg/mL allow us to
      predict the presence of CAC in these patients.

PMID- 19574343
TI  - Quantitative trait loci predicting circulating sex steroid hormones in men from
      the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
AB  - Twin studies suggest a heritable component to circulating sex steroid hormones
      and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer
      Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone
      pathway were examined in relation to circulating levels of SHBG (N = 4720),
      testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta
      estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly
      associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with
      previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of
      26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers.
      Further noteworthy novel findings were observed between SNPs in ESR1 with
      testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and
      SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference =
      11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone
      pathway is associated with differences in circulating SHBG and sex steroid
      hormones.

PMID- 19574344
TI  - Health behaviors from early to late midlife as predictors of cognitive function:
      The Whitehall II study.
AB  - The authors examined associations of health behaviors over a 17-year period,
      separately and in combination, with cognition in late midlife in 5,123 men and
      women from the Whitehall II study (United Kingdom). Health behaviors were
      assessed in early midlife (mean age = 44 years; phase 1, 1985-1988), in midlife
      (mean age = 56 years; phase 5, 1997-1999), and in late midlife (mean age = 61
      years; phase 7, 2002-2004). A score of the number of unhealthy behaviors
      (smoking, alcohol abstinence, low physical activity, and low fruit and vegetable
      consumption) was defined as ranging from 0 to 4. Poor (defined as scores in the
      worst sex-specific quintile) executive function and memory in late midlife (phase
      7) were analyzed as outcomes. Compared with those with no unhealthy behaviors,
      those with 3-4 unhealthy behaviors at phase 1 (odds ratio (OR) = 1.84, 95%
      confidence interval (CI): 1.27, 2.65), phase 5 (OR = 2.38, 95% CI: 1.76, 3.22),
      and phase 7 (OR = 2.76, 95% CI: 2.04, 3.73) were more likely to have poor
      executive function. A similar association was observed for memory. The odds of
      poor executive function and memory were the greater the more times the
      participant reported unhealthy behaviors over the 3 phases. This study suggests
      that both the number of unhealthy behaviors and their duration are associated
      with subsequent cognitive function in later life.

PMID- 19574345
TI  - Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside.
AB  - The serine/threonine protein kinase, mammalian target of rapamycin (mTOR) is
      regulated by insulin and nutrient availability and has been proposed to play a
      central role as a nutrient sensor in skeletal muscle. mTOR associates with its
      binding partners, raptor and rictor, to form two structurally and functionally
      distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)
      respectively. We have investigated the assembly of mTORC1/2 and the activation of
      their downstream substrates (i.e. Akt, S6K1) in response to known effectors of
      mTOR, excess lipid availability and AMP-activated protein kinase (AMPK)
      activation/exercise training in rat skeletal muscle. The in vivo formation of
      mTORC1 and 2 and the activation of their respective downstream substrates were
      increased in response to chronic (8 weeks) consumption of a high-fat diet. Diet
      induced mTORC activation and skeletal muscle insulin resistance were reversed by
      4 weeks of exercise training, which was associated with enhanced muscle AMPK
      activation. In order to determine whether AMPK activation reverses lipid-induced
      mTOR activation, L6 myotubes were exposed to 0.4 mM palmitate to activate
      mTORC1/2 in the absence or presence of 5'-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR). Palmitate exposure (4 h) increased insulin-stimulated
      S6K1 Thr389 phosphorylation by 60%, indicating activation of mTORC1. AMPK
      activation with 1 mM AICAR abolished lipid-induced mTOR activation in vitro. Our
      data implicates reductions in mTOR complex activation with the reversal of lipid
      induced skeletal muscle insulin resistance in response to exercise training or
      AICAR and identifies mTOR as a potential target for the treatment of insulin
      resistance.

PMID- 19574347
TI  - Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in
      ferrets and mice.
AB  - Recent reports of mild to severe influenza-like illness in humans caused by a
      novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better
      understand the pathogenesis and transmission of these viruses in mammals. In this
      study, selected 2009 A(H1N1) influenza isolates were assessed for their ability
      to cause disease in mice and ferrets and compared with a contemporary seasonal
      H1N1 virus for their ability to transmit to naive ferrets through respiratory
      droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza
      viruses caused increased morbidity, replicated to higher titers in lung tissue,
      and were recovered from the intestinal tract of intranasally inoculated ferrets.
      The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet
      transmission in ferrets in comparison with the highly transmissible phenotype of
      a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was
      further corroborated by characterizing the binding specificity of the viral
      hemagglutinin to the sialylated glycan receptors (in the human host) by use of
      dose-dependent direct receptor-binding and human lung tissue-binding assays.

PMID- 19574346
TI  - Detection of 16 gamma-ray pulsars through blind frequency searches using the
      Fermi LAT.
AB  - Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation
      across the electromagnetic spectrum. Although there are more than 1800 known
      radio pulsars, until recently only seven were observed to pulse in gamma rays,
      and these were all discovered at other wavelengths. The Fermi Large Area
      Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma
      ray pulsations. We report the detection of 16 gamma-ray pulsars in blind
      frequency searches using the LAT. Most of these pulsars are coincident with
      previously unidentified gamma-ray sources, and many are associated with supernova
      remnants. Direct detection of gamma-ray pulsars enables studies of emission
      mechanisms, population statistics, and the energetics of pulsar wind nebulae and
      supernova remnants.

PMID- 19574348
TI  - Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in
      ferrets.
AB  - The swine-origin A(H1N1) influenza virus that has emerged in humans in early 2009
      has raised concerns about pandemic developments. In a ferret pathogenesis and
      transmission model, the 2009 A(H1N1) influenza virus was found to be more
      pathogenic than a seasonal A(H1N1) virus, with more extensive virus replication
      occurring in the respiratory tract. Replication of seasonal A(H1N1) virus was
      confined to the nasal cavity of ferrets, but the 2009 A(H1N1) influenza virus
      also replicated in the trachea, bronchi, and bronchioles. Virus shedding was more
      abundant from the upper respiratory tract for 2009 A(H1N1) influenza virus as
      compared with seasonal virus, and transmission via aerosol or respiratory
      droplets was equally efficient. These data suggest that the 2009 A(H1N1)
      influenza virus has the ability to persist in the human population, potentially
      with more severe clinical consequences.

PMID- 19574350
TI  - The dynamics of phenotypic change and the shrinking sheep of St. Kilda.
AB  - Environmental change, including climate change, can cause rapid phenotypic change
      via both ecological and evolutionary processes. Because ecological and
      evolutionary dynamics are intimately linked, a major challenge is to identify
      their relative roles. We exactly decomposed the change in mean body weight in a
      free-living population of Soay sheep into all the processes that contribute to
      change. Ecological processes contribute most, with selection--the underpinning of
      adaptive evolution--explaining little of the observed phenotypic trend. Our
      results enable us to explain why selection has so little effect even though
      weight is heritable, and why environmental change has caused a decline in the
      body size of Soay sheep.

PMID- 19574352
TI  - An opportunity we cannot waste.

PMID- 19574349
TI  - A population of gamma-ray millisecond pulsars seen with the Fermi Large Area
      Telescope.
AB  - Pulsars are born with subsecond spin periods and slow by electromagnetic braking
      for several tens of millions of years, when detectable radiation ceases. A second
      life can occur for neutron stars in binary systems. They can acquire mass and
      angular momentum from their companions, to be spun up to millisecond periods and
      begin radiating again. We searched Fermi Large Area Telescope data for pulsations
      from all known millisecond pulsars (MSPs) outside of globular clusters, using
      rotation parameters from radio telescopes. Strong gamma-ray pulsations were
      detected for eight MSPs. The gamma-ray pulse profiles and spectral properties
      resemble those of young gamma-ray pulsars. The basic emission mechanism seems to
      be the same for MSPs and young pulsars, with the emission originating in regions
      far from the neutron star surface.

PMID- 19574353
TI  - Carbon trading. House vote seen as big step toward cooling the greenhouse.

PMID- 19574354
TI  - Pandemic influenza. Ferrets shed light on new virus's severity and spread.

PMID- 19574355
TI  - SBIR program. Researchers fight against bigger slice to small business.

PMID- 19574357
TI  - Budget cuts. Proposal to slash salaries riles California researchers.

PMID- 19574358
TI  - 2010 budget. House panel cuts DOE education program.

PMID- 19574359
TI  - NSF Antarctic logistics. A hot competition for a cold contract.

PMID- 19574361
TI  - Pharmaceuticals. Betting on biotech to transform Guangdong, China's export hub.

PMID- 19574362
TI  - Paleoanthropology. Still seeking Peking Man.

PMID- 19574363
TI  - China. Archaeologists seek new clues to the riddle of Emperor Qin's terra-cotta
      army.

PMID- 19574364
TI  - Origins. On the origin of the nervous system.

PMID- 19574365
TI  - Newsmaker interview. Behavioral geneticist celebrates twins, scorns PC science.
      Interview by Constance Holden.

PMID- 19574366
TI  - Ethics. Private money, public disclosure.

PMID- 19574367
TI  - Ethics. Senate probe of research psychiatrists.

PMID- 19574351
TI  - Radio imaging of the very-high-energy gamma-ray emission region in the central
      engine of a radio galaxy.
AB  - The accretion of matter onto a massive black hole is believed to feed the
      relativistic plasma jets found in many active galactic nuclei (AGN). Although
      some AGN accelerate particles to energies exceeding 10(12) electron volts and are
      bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known
      where the VHE emission originates. Here we report on radio and VHE observations
      of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma
      ray flares accompanied by a strong increase of the radio flux from its nucleus.
      These results imply that charged particles are accelerated to very high energies
      in the immediate vicinity of the black hole.

PMID- 19574368
TI  - Taxonomy. China searches for an 11th-hour lifesaver for a dying discipline.

PMID- 19574369
TI  - Heliophysics missions show promise.

PMID- 19574370
TI  - Standing the test of time variations.

PMID- 19574371
TI  - How the gray wolf got its color.

PMID- 19574373
TI  - Genetics. The illusive gold standard in genetic ancestry testing.

PMID- 19574374
TI  - Neuroscience. Remembering outside the box.

PMID- 19574375
TI  - Ecology. Insect conservation.

PMID- 19574376
TI  - Applied physics. Coherent holes in a semiconductor quantum dot.

PMID- 19574377
TI  - Geophysics. How did Earth accrete?

PMID- 19574378
TI  - Transcription. Sweet silencing.

PMID- 19574379
TI  - Oceans. Predicting El Nino's Impacts.

PMID- 19574380
TI  - How to think, say, or do precisely the worst thing for any occasion.
AB  - In slapstick comedy, the worst thing that could happen usually does: The person
      with a sore toe manages to stub it, sometimes twice. Such errors also arise in
      daily life, and research traces the tendency to do precisely the worst thing to
      ironic processes of mental control. These monitoring processes keep us watchful
      for errors of thought, speech, and action and enable us to avoid the worst thing
      in most situations, but they also increase the likelihood of such errors when we
      attempt to exert control under mental load (stress, time pressure, or
      distraction). Ironic errors in attention and memory occur with identifiable brain
      activity and prompt recurrent unwanted thoughts; attraction to forbidden desires;
      expression of objectionable social prejudices; production of movement errors; and
      rebounds of negative experiences such as anxiety, pain, and depression. Such
      ironies can be overcome when effective control strategies are deployed and mental
      load is minimized.

PMID- 19574381
TI  - Serengeti birds maintain forests by inhibiting seed predators.
AB  - Of fundamental interest in conservation ecology are the regulatory mechanisms
      that maintain communities. We document a mechanism that maintains forests in the
      Serengeti ecosystem, Tanzania, and the destabilization when disturbance opens
      forest canopy. Forest birds, by consuming seeds, protected them from beetle
      attack. Consumption increased the germination rate and the density of seedlings
      and recruits, which was sufficient to maintain the forest. Opening of the canopy
      resulted in loss of birds, increased beetle attack, and loss of germination.
      Thus, frugivorous birds are necessary for the maintenance of forests. Their
      absence could have resulted in the observed forest decline since 1966.

PMID- 19574382
TI  - Dissociable components of rule-guided behavior depend on distinct medial and
      prefrontal regions.
AB  - Much of our behavior is guided by rules. Although human prefrontal cortex (PFC)
      and anterior cingulate cortex (ACC) are implicated in implementing rule-guided
      behavior, the crucial contributions made by different regions within these areas
      are not yet specified. In an attempt to bridge human neuropsychology and nonhuman
      primate neurophysiology, we report the effects of circumscribed lesions to
      macaque orbitofrontal cortex (OFC), principal sulcus (PS), superior dorsolateral
      PFC, ventrolateral PFC, or ACC sulcus, on separable cognitive components of a
      Wisconsin Card Sorting Test (WCST) analog. Only the PS lesions impaired
      maintenance of abstract rules in working memory; only the OFC lesions impaired
      rapid reward-based updating of representations of rule value; the ACC sulcus
      lesions impaired active reference to the value of recent choice-outcomes during
      rule-based decision-making.

PMID- 19574383
TI  - H2O at the Phoenix landing site.
AB  - The Phoenix mission investigated patterned ground and weather in the northern
      arctic region of Mars for 5 months starting 25 May 2008 (solar longitude between
      76.5 degrees and 148 degrees ). A shallow ice table was uncovered by the robotic
      arm in the center and edge of a nearby polygon at depths of 5 to 18 centimeters.
      In late summer, snowfall and frost blanketed the surface at night; H(2)O ice and
      vapor constantly interacted with the soil. The soil was alkaline (pH = 7.7) and
      contained CaCO(3), aqueous minerals, and salts up to several weight percent in
      the indurated surface soil. Their formation likely required the presence of
      water.

PMID- 19574384
TI  - Evidence for calcium carbonate at the Mars Phoenix landing site.
AB  - Carbonates are generally products of aqueous processes and may hold important
      clues about the history of liquid water on the surface of Mars. Calcium carbonate
      (approximately 3 to 5 weight percent) has been identified in the soils around the
      Phoenix landing site by scanning calorimetry showing an endothermic transition
      beginning around 725 degrees C accompanied by evolution of carbon dioxide and by
      the ability of the soil to buffer pH against acid addition. Based on empirical
      kinetics, the amount of calcium carbonate is most consistent with formation in
      the past by the interaction of atmospheric carbon dioxide with liquid water films
      on particle surfaces.

PMID- 19574385
TI  - Detection of perchlorate and the soluble chemistry of martian soil at the Phoenix
      lander site.
AB  - The Wet Chemistry Laboratory on the Phoenix Mars Lander performed aqueous
      chemical analyses of martian soil from the polygon-patterned northern plains of
      the Vastitas Borealis. The solutions contained approximately 10 mM of dissolved
      salts with 0.4 to 0.6% perchlorate (ClO4) by mass leached from each sample. The
      remaining anions included small concentrations of chloride, bicarbonate, and
      possibly sulfate. Cations were dominated by Mg2+ and Na+, with small
      contributions from K+ and Ca2+. A moderately alkaline pH of 7.7 +/- 0.5 was
      measured, consistent with a carbonate-buffered solution. Samples analyzed from
      the surface and the excavated boundary of the approximately 5-centimeter-deep ice
      table showed no significant difference in soluble chemistry.

PMID- 19574386
TI  - Mars water-ice clouds and precipitation.
AB  - The light detection and ranging instrument on the Phoenix mission observed water
      ice clouds in the atmosphere of Mars that were similar to cirrus clouds on Earth.
      Fall streaks in the cloud structure traced the precipitation of ice crystals
      toward the ground. Measurements of atmospheric dust indicated that the planetary
      boundary layer (PBL) on Mars was well mixed, up to heights of around 4
      kilometers, by the summer daytime turbulence and convection. The water-ice clouds
      were detected at the top of the PBL and near the ground each night in late summer
      after the air temperature started decreasing. The interpretation is that water
      vapor mixed upward by daytime turbulence and convection forms ice crystal clouds
      at night that precipitate back toward the surface.

PMID- 19574387
TI  - A coherent single-hole spin in a semiconductor.
AB  - Semiconductors have uniquely attractive properties for electronics and photonics.
      However, it has been difficult to find a highly coherent quantum state in a
      semiconductor for applications in quantum sensing and quantum information
      processing. We report coherent population trapping, an optical quantum
      interference effect, on a single hole. The results demonstrate that a hole spin
      in a quantum dot is highly coherent.

PMID- 19574388
TI  - Impact of shifting patterns of Pacific Ocean warming on North Atlantic tropical
      cyclones.
AB  - Two distinctly different forms of tropical Pacific Ocean warming are shown to
      have substantially different impacts on the frequency and tracks of North
      Atlantic tropical cyclones. The eastern Pacific warming (EPW) is identical to
      that of the conventional El Nino, whereas the central Pacific warming (CPW) has
      maximum temperature anomalies located near the dateline. In contrast to EPW
      events, CPW episodes are associated with a greater-than-average frequency and
      increasing landfall potential along the Gulf of Mexico coast and Central America.
      Differences are shown to be associated with the modulation of vertical wind shear
      in the main development region forced by differential teleconnection patterns
      emanating from the Pacific. The CPW is more predictable than the EPW, potentially
      increasing the predictability of cyclones on seasonal time scales.

PMID- 19574389
TI  - Role of layer 6 of V2 visual cortex in object-recognition memory.
AB  - Cellular responses in the V2 secondary visual cortex to simple as well as complex
      visual stimuli have been well studied. However, the role of area V2 in visual
      memory remains unexplored. We found that layer 6 neurons of V2 are crucial for
      the processing of object-recognition memory (ORM). Using the protein regulator of
      G protein signaling-14 (RGS-14) as a tool, we found that the expression of this
      protein into layer 6 neurons of rat-brain area V2 promoted the conversion of a
      normal short-term ORM that normally lasts for 45 minutes into long-term memory
      detectable even after many months. Furthermore, elimination of the same-layer
      neurons by means of injection of a selective cytotoxin resulted in the complete
      loss of normal as well as protein-mediated enhanced ORM.

PMID- 19574390
TI  - Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA
      splicing.
AB  - The finding that the metazoan hypoxic response is regulated by oxygen-dependent
      posttranslational hydroxylations, which regulate the activity and lifetime of
      hypoxia-inducible factor (HIF), has raised the question of whether other
      hydroxylases are involved in the regulation of gene expression. We reveal that
      the splicing factor U2 small nuclear ribonucleoprotein auxiliary factor 65
      kilodalton subunit (U2AF65) undergoes posttranslational lysyl-5-hydroxylation
      catalyzed by the Fe(II) and 2-oxoglutarate-dependent dioxygenase Jumonji domain-6
      protein (Jmjd6). Jmjd6 is a nuclear protein that has an important role in
      vertebrate development and is a human homolog of the HIF asparaginyl-hydroxylase.
      Jmjd6 is shown to change alternative RNA splicing of some, but not all, of the
      endogenous and reporter genes, supporting a specific role for Jmjd6 in the
      regulation of RNA splicing.

PMID- 19574391
TI  - Ligand-gated chloride channels are receptors for biogenic amines in C. elegans.
AB  - Biogenic amines such as serotonin and dopamine are intercellular signaling
      molecules that function widely as neurotransmitters and neuromodulators. We have
      identified in the nematode Caenorhabditis elegans three ligand-gated chloride
      channels that are receptors for biogenic amines: LGC-53 is a high-affinity
      dopamine receptor, LGC-55 is a high-affinity tyramine receptor, and LGC-40 is a
      low-affinity serotonin receptor that is also gated by choline and acetylcholine.
      lgc-55 mutants are defective in a behavior that requires endogenous tyramine,
      which indicates that this ionotropic tyramine receptor functions in tyramine
      signaling in vivo. Our studies suggest that direct activation of membrane
      chloride conductances is a general mechanism of action for biogenic amines in the
      modulation of C. elegans behavior.

PMID- 19574394
TI  - Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term
      potentiation and spatial reversal learning.
AB  - Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely
      complementary distribution in the mature rodent brain and tend to segregate to
      synapses with different physiological properties. In the hippocampus, VGLUT1 is
      the dominate subtype in adult animals, whereas VGLUT2 is transiently expressed
      during early postnatal development. We generated and characterized VGLUT1
      knockout mice in order to examine the functional contribution of this transporter
      to hippocampal synaptic plasticity and hippocampus-dependent spatial learning.
      Because complete deletion of VGLUT1 resulted in postnatal lethality, we used
      heterozygous animals for analysis. Here, we report that deletion of VGLUT1
      resulted in impaired hippocampal long-term potentiation (LTP) in the CA1 region
      in vitro. In contrast, heterozygous VGLUT2 mice that were investigated for
      comparison did not show any changes in LTP. The reduced ability of VGLUT1
      deficient mice to express LTP was accompanied by a specific deficit in spatial
      reversal learning in the water maze. Our data suggest a functional role of VGLUT1
      in forms of hippocampal synaptic plasticity that are required to adapt and modify
      acquired spatial maps to external stimuli and changes.

PMID- 19574393
TI  - Auditory attentional control and selection during cocktail party listening.
AB  - In realistic auditory environments, people rely on both attentional control and
      attentional selection to extract intelligible signals from a cluttered
      background. We used functional magnetic resonance imaging to examine auditory
      attention to natural speech under such high processing-load conditions.
      Participants attended to a single talker in a group of 3, identified by the
      target talker's pitch or spatial location. A catch-trial design allowed us to
      distinguish activity due to top-down control of attention versus attentional
      selection of bottom-up information in both the spatial and spectral (pitch)
      feature domains. For attentional control, we found a left-dominant fronto
      parietal network with a bias toward spatial processing in dorsal precentral
      sulcus and superior parietal lobule, and a bias toward pitch in inferior frontal
      gyrus. During selection of the talker, attention modulated activity in left
      intraparietal sulcus when using talker location and in bilateral but right
      dominant superior temporal sulcus when using talker pitch. We argue that these
      networks represent the sources and targets of selective attention in rich
      auditory environments.

PMID- 19574395
TI  - Sertoli cell androgen receptor DNA binding domain is essential for the completion
      of spermatogenesis.
AB  - We examined the biological importance of Sertoli cell androgen receptor (AR)
      genomic interaction, using a Cre-loxP approach to selectively disrupt the AR DNA
      binding domain (AR-DBD). Sertoli cell (SC)-specific transgenic Abpa or AMH
      promoters targeted Cre-mediated inframe excision of mouse Ar exon-3, encoding the
      AR-DBD second zinc-finger (ZF2), generating SC-specific mutant AR(DeltaZF2) lines
      designated Abp.SCAR(DeltaZF2) and AMH.SCAR(DeltaZF2), respectively. Both
      SCAR(DeltaZF2) lines produced infertile males exhibiting spermatogenic arrest,
      despite normal SC numbers and immunolocalized SC nuclear AR. Adult homozygous
      TgCre((+/+)) SCAR(DeltaZF2) or double-TgCre((+/-)) Abp/AMH.SCAR(DeltaZF2) males
      displayed equivalent small testes 30% of normal size, representing maximal Cre
      loxP-disruption of Sertoli AR function. Hemizygous TgCre((+/-)) vs. homozygous
      TgCre((+/+)) Abp.SCAR(DeltaZF2) testes were larger (47% normal size) with more
      postmeiotic development, indicating dose-dependent Cre-mediated disruption of SC
      specific AR-DBD activity. SCAR(DeltaZF2) males exhibited adult Leydig cell
      hypertrophy but normal serum testosterone levels. Sertoli cell-specific Rhox5 and
      Spinlw1 transcription, regulated by divergent or classical androgen-response
      elements, respectively, were both decreased in postnatal SCAR(DeltaZF2) vs.
      control testes, demonstrating SC-specific AR-DBD function as early as postnatal d
      5. However, Rhox5 expression declined dose-dependently, whereas Spinlw1
      expression increased, in adult TgCre((+/-)) and TgCre((+/+)) SCAR(DeltaZF2)
      testes, revealing differential temporal control for distinct AR-regulated
      transcripts. Androgen-repressed Ngfr was not up-regulated in SCAR(DeltaZF2)
      testes, suggesting maintenance of a nonclassical mechanism independent of AR-DBD.
      Thus, our unique SCAR(DeltaZF2) paradigm provided dose-dependent Cre-mediated
      disruption of testicular development and gene expression revealing that the AR
      DBD is essential for SC function and postmeiotic spermatogenesis. Nongenomic or
      AR-DBD-independent pathways appear secondary or play no major independent role in
      SC function.

PMID- 19574396
TI  - Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a
      neurocircuit involving the vagus nerve.
AB  - Recent evidence suggests that hormones such as insulin and leptin act in the
      hypothalamus to regulate energy balance and glucose metabolism. Here we show that
      in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats, adenovirally induced
      expression of leptin receptors in the area of the hypothalamic arcuate nucleus
      improved peripheral insulin sensitivity via enhanced suppression of hepatic
      glucose production, with no change of insulin-stimulated glucose uptake or
      disposal. This effect was associated with increased insulin signal transduction
      via phosphatidylinositol-3-OH kinase (as measured by pY-insulin receptor
      substrate-1 and pS-PKB/Akt) in liver, but not skeletal muscle, and with reduced
      hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and
      phosphoenolpyruvate kinase. Moreover, the beneficial effects of hypothalamic
      leptin signaling on hepatic insulin sensitivity were blocked by selective hepatic
      vagotomy. We conclude that hypothalamic leptin action increases peripheral
      insulin sensitivity primarily via effects on the liver and that the mechanism
      underlying this effect is dependent on the hepatic branch of the vagus nerve.

PMID- 19574398
TI  - Metformin inhibits aromatase via an extracellular signal-regulated kinase
      mediated pathway.
AB  - Metformin treatment, now widely prescribed in polycystic ovary syndrome, is aimed
      at correcting the associated insulin resistance, but it has also been shown to
      directly inhibit ovarian steroidogenesis. The mechanisms, however, by which
      metformin inhibits estradiol production in human granulosa cells remains unknown.
      Granulosa luteal cells were incubated with metformin, insulin, or combined
      metformin and insulin treatment, and aromatase mRNA expression was quantified
      using real-time RT-PCR. Enzyme activity was assessed by the conversion of (3)H
      androstenedione to estrone and estradiol. Metformin's effect on the expression of
      specific untranslated first exon aromatase promoters was analyzed using
      semiquantitative PCR. The involvement of MAPK kinase (MEK)/ERK pathway was
      investigated by immunoblotting for aromatase, phosphorylated, and total ERK-1,2
      from cells cultured as above with/without the MEK inhibitor PD98059. Metformin
      significantly inhibited basal and insulin-stimulated aromatase mRNA expression,
      with parallel results from the aromatase activity assay and protein assessment.
      This suppression was via down-regulation of aromatase promoter II, I.3, and 1.4
      expression and was reversed by the addition of PD98059. Involvement of the ERK
      signaling pathway was demonstrated by the significant increase in phosphorylated
      ERK-1,2 with the combined metformin and insulin treatment. We have shown for the
      first time in human granulosa cells that metformin signficantly attenuated basal
      and insulin-stimulated P450 aromatase mRNA expression and activity, via silencing
      of key promoters. This occurred by activation of MEK/ERK pathway, which
      negatively regulated aromatase production. This is an important consideration
      given metformin's widespread use in polycystic ovary syndrome and may further
      support a possible therapeutic indication in estrogen-dependent breast tumors.

PMID- 19574397
TI  - An in vivo study on adjudin and blood-testis barrier dynamics.
AB  - Adjudin is known to specifically affect Sertoli-germ cell adhesion, resulting in
      germ cell loss from the seminiferous epithelium and transient infertility. The
      apical ectoplasmic specialization (ES) was shown to be the primary target of
      adjudin because adhesion was unaffected in organs that lack this structure.
      Herein we expand previous findings by treating rat pups with adjudin, and we
      aimed to address two questions. First, can adjudin perturb germ cell adhesion in
      the seminiferous epithelium of testes in which the apical ES is not yet present?
      Second, can adjudin affect assembly of the blood-testis barrier (BTB) at 15-18 d
      of age? Interesting changes were noted when aged-matched testes from control and
      adjudin-treated rats were examined, including a delay in the appearance of
      developing germ cells as well as a delay in the formation of the tubule lumen.
      Immunoblotting using antibodies against BTB-constituent proteins indicated that
      formation of the BTB was affected in rat pups gavaged with adjudin. These results
      were corroborated by immunofluorescence microscopy, which showed profound changes
      in the cellular distribution of tight junction and basal ES proteins. Moreover,
      the BTB was shown to be compromised in 30-d-old rats when its integrity was
      assessed by a functional in vivo assay. By 45 d of age, however, the seminiferous
      epithelium of treated rats was indistinguishable from that of control rats.
      Collectively these results demonstrate that adjudin targets the apical ES as well
      as the basal ES and tight junction, which in turn delays assembly of the BTB.

PMID- 19574399
TI  - Gonadotropin-releasing hormone-mediated phosphorylation of estrogen receptor
      alpha contributes to fosB expression in mouse gonadotrophs.
AB  - Estrogen receptors (ERs) are activated by their ligands as well as signaling
      pathways that alter ER phosphorylation in response to peptide hormones and growth
      factors. In pituitary gonadotrophs, GnRHs act via the type I GnRH receptor
      (GnRHR). Both GnRH subtypes (GnRH-I and -II) activate an estrogen response
      element (ERE)-driven luciferase reporter gene in LbetaT2 mouse pituitary cells,
      and GnRH-I is most potent in this regard. Moreover, antide (a GnRH antagonist)
      and a GnRHR small interfering RNA (siRNA) abrogate this effect, whereas an
      ERalpha antagonist (ICI 182,780) does not. The ERalpha in LbetaT2 cells is
      phosphorylated at Ser(118) in the nucleus and at Ser(167) in both nucleus and
      cytoplasm after GnRH treatments and coincided with increased ERalpha binding to
      its coactivator, the p300/cAMP response element-binding protein-associated factor
      (PCAF). Moreover, siRNA-mediated knockdown of PCAF levels attenuated GnRH-induced
      ERE-luciferase transactivation in these cells. Most importantly, both GnRH
      subtypes robustly up-regulated expression of the immediate early response gene,
      fosB, whereas cotreatment with ERalpha siRNA or PCAF siRNA attenuated this
      effect. This appears to occur at the transcriptional level because corecruitment
      of ERalpha and PCAF to an ERE within the endogenous fosB promoter was increased
      by GnRH treatments, as shown by chromatin immunoprecipitation assays. These data
      demonstrate that GnRH-mediated phosphorylation of ERalpha in mouse LbetaT2
      pituitary cells results in its rapid association with PCAF and the
      transcriptional activation of fosB, and we demonstrate that this in turn likely
      activates other genes in pituitary cells including the FSH beta-subunit gene.

PMID- 19574400
TI  - Minireview: epigenetic changes in ovarian cancer.
AB  - Epigenetic aberrations, including DNA methylation, histone modifications, and
      micro-RNA dysregulation, are now well established in the development and
      progression of ovarian cancer, and their gradual accumulation is associated with
      advancing disease stage and grade. Epigenetic aberrations are relatively stable,
      associated with distinct disease subtypes, and present in circulating serum,
      representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. In
      contrast to DNA mutations and deletions, aberrant gene-repressive epigenetic
      modifications are potentially reversible by epigenetic therapies, including
      inhibitors of DNA methylation or histone-modifying enzymes. Although epigenetic
      monotherapies have not shown activity against solid tumors, including ovarian
      cancer, preclinical studies suggest they will be effective when used in
      combination with one another or with conventional chemotherapeutics, and
      combinatorial epigenetic therapy regiments are being examined in cancer clinical
      trials. A greater understanding of the role of epigenetics in ovarian neoplasia
      will provide for improved interventions against this devastating malignancy.

PMID- 19574401
TI  - Insulin receptor substrate-2 in beta-cells decreases diabetes in nonobese
      diabetic mice.
AB  - Insulin receptor substrate-2 (Irs2) integrates insulin-like signals with glucose
      and cAMP agonists to regulate beta-cell growth, function, and survival. This
      study investigated whether increased Irs2 concentration in beta-cells could
      reduce beta-cell destruction and the incidence of type 1 diabetes in nonobese
      diabetic (NOD) mice. NOD mice were intercrossed with C57BL/6 mice overexpressing
      Irs2 specifically in beta-cells to create NOD(Irs2) mice. After backcrossing
      NOD(Irs2) mice for 12 generations, glucose homeostasis and diabetes incidence
      were compared against NOD littermates. Compared with 12-wk-old NOD mice, the
      progression of severe insulitis was reduced and islet mass was increased in
      NOD(Irs2) mice. Moreover, the risk of diabetes decreased 50% in NOD(Irs2) mice
      until the experiment was terminated at 40 wk of age. Nondiabetic NOD(Irs2) mice
      displayed better glucose tolerance than nondiabetic NOD mice throughout the
      duration of the study and up to the age of 18 months. The effect of Irs2 to
      increase islet mass and improve glucose tolerance raised the possibility that
      NOD(Irs2) mice might have an increased capacity to respond to anti-CD3 antibody,
      which can induce remission of overt diabetes in some NOD mice. Anti-CD3 antibody
      injections restored glucose tolerance in newly diabetic NOD and NOD(Irs2) mice;
      however, anti-CD3-treated NOD(Irs2) mice were less likely than NOD mice to
      relapse during the experimental period because they displayed 10-fold greater
      beta-cell mass and mitogenesis. In conclusion, increased Irs2 attenuated the
      progression of beta-cell destruction, promoted beta-cell mitogenesis, and reduced
      diabetes incidence in NOD(Irs2) mice.

PMID- 19574402
TI  - The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy
      2/seipin plays a key role in adipocyte differentiation.
AB  - Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are
      the underlying defect in patients with congenital generalized lipodystrophy type
      2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In
      this study, we investigated the role of Bscl2 in the regulation of adipocyte
      differentiation. Bscl2 mRNA is highly up-regulated during standard hormone
      induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does
      not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the
      preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells
      has no effect on bone morphogenetic protein-4-induced preadipocyte commitment.
      However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard
      hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome
      proliferator-activated receptor-gamma agonist pioglitazone at an early stage of
      differentiation. Interestingly, pioglitazone-induced differentiation in the
      absence of standard hormone is not associated with up-regulated Bscl2 expression.
      On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks
      pioglitazone-induced adipose differentiation. These experiments suggest that
      Bscl2 may be essential for normal adipogenesis; it works upstream or at the level
      of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert
      its full activity during adipogenesis. Loss of Bscl2 function thus interferes
      with the normal transcriptional cascade of adipogenesis during fat cell
      differentiation, resulting in near total loss of fat or lipodystrophy.

PMID- 19574405
TI  - Efficacy of a single computer-tailored e-mail for smoking cessation: results
      after 6 months.
AB  - To date, few Internet-delivered smoking cessation interventions have been tested.
      This study tested the efficacy, understandability, credibility and personal
      relevance of an e-mail-delivered computer-tailored smoking cessation
      intervention. It included tailored action plan feedback, as recent studies have
      demonstrated the importance of planning in facilitating quitting smoking.
      Participants (Dutch adults) were randomly assigned to the intervention (computer
      tailored e-mail; N = 224) or the control group (generic, non-tailored e-mail; N =
      234). The results 6 months after baseline (N = 195) showed that significantly
      more participants in the intervention group reported not having smoked in the
      last 24 hours (21.5%) and 7 days (20.4%) in contrast with participants in the
      control group (9.8 and 7.8%, respectively). Intention-to-treat analyses revealed
      similar results, though overall lower quitting percentages. Furthermore,
      participants in the intervention group appreciated the computer-tailored e-mail
      significantly more in terms of understandability, credibility and personal
      relevance. Hence, the computer-tailored intervention is effective for the Dutch
      smoking population motivated to quit smoking. Further research is needed into the
      efficacy of the intervention for smokers who are not motivated to quit smoking
      and into the benefits of (multiple) e-mail-delivered tailored letters with
      tailored action plan feedback over and above tailoring without action plan
      feedback.

PMID- 19574403
TI  - Developmental changes in pituitary adenylate cyclase activating polypeptide
      expression during the perinatal period: possible role in fetal gonadotroph
      regulation.
AB  - Normal reproductive functioning may require secretion of LH independently of FSH.
      Variation in GnRH pulse frequency and inhibin negative feedback are mechanisms
      for differential gonadotropin regulation; however, the first instance of
      differential regulation in rats is during fetal development, prior to the
      establishment of GnRH connections, when LH accumulates appreciably 2-4 d prior to
      FSH. Pituitary adenylate cyclase activating polypeptide (PACAP) can
      differentially regulate the gonadotropins in vitro by stimulating alpha-subunit
      transcription, lengthening LHbeta transcripts and decreasing FSHbeta mRNA levels,
      probably through stimulation of follistatin transcription. These experiments are
      the first to examine whether PACAP influences gonadotroph function in perinatal
      pituitaries. In vivo, pituitary PACAP mRNA and peptide levels were high at
      embryonic d 19 and declined by 94 and 85%, respectively, after parturition. This
      was accompanied by a decrease of 65 and 96% in total follistatin and follistatin
      288 mRNAs. These changes were temporally associated with a 20- and 6.5-fold rise
      in FSHbeta and GnRH receptor mRNAs, respectively, with no significant increase in
      LHbeta mRNA. In pituitary cell cultures from fetal and postnatal male rats, PACAP
      mRNA levels were likewise highest in fetal cultures in which the PACAP 6-38
      antagonist decreased alpha-subunit and increased FSHbeta mRNA. PACAP 6-38 also
      reduced basal and GnRH-stimulated LH secretion with little effect on FSH. These
      data support the hypothesis that PACAP expressed at high levels in the fetal
      pituitary stimulates alpha-subunit expression and LH secretion and restrains FSH
      synthesis relative to LH and that a decline in PACAP allows for the neonatal rise
      in FSH and GnRH receptor because follistatin is decreased.

PMID- 19574404
TI  - Effects of maternal global nutrient restriction on fetal baboon hepatic insulin
      like growth factor system genes and gene products.
AB  - Knowledge of altered maternal nutrition effects on growth-regulating systems is
      critical to understanding normal and abnormal fetal development. There are many
      reports of hepatic fetal IGF system responses to maternal nutrient restriction
      (MNR) during pregnancy in rodents and sheep but none in nonhuman primates. We
      determined effects of MNR on the fetal baboon hepatic IGF system. Social groups
      of female baboons were fed ad libitum, controls, or 70% controls (MNR) from 0.16
      to 0.5 gestation and fetuses delivered by cesarean section. Fetal liver tissue
      was analyzed for IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 mRNA by in situ
      hybridization and quantitative RT-PCR and protein by immunohistochemistry (IHC);
      IGF-I receptor, IGF-II receptor by quantitative RT-PCR and IHC and IGFBP-1 by in
      situ hybridization and IHC. MNR did not alter fetal body or liver weight. Fetal
      hepatic glycogen staining increased with MNR. MNR reduced fetal hepatic IGF-I and
      IGF-II and increased IGFBP-1 mRNA and decreased IGF-I, IGF-II, IGF-I receptor,
      and IGF-II receptor protein and increased protein for IGFBP-1 and IGFBP-3. MNR
      increased caspase-3, indicating apoptosis and decreased Akt staining, indicating
      decreased nutrient sensing. In conclusion, whereas fetal body and liver weights
      did not change in response to moderate MNR during the first half of baboon
      pregnancy, the major indices of function of the hepatic IGF system measured were
      all reduced.

PMID- 19574406
TI  - 'My friends love to tan': examining sensation seeking and the mediating role of
      association with friends who use tanning beds on tanning bed use intentions.
AB  - This paper explored how sensation seeking contributes to the likelihood of
      tanning bed use intentions both directly and indirectly through the way it shapes
      interaction with peers who use tanning beds and attitudes toward tanning bed.
      Eight hundred and ninety six (n = 896) male and female college students were
      recruited for the study. Measured variables included sensation seeking,
      association with friends who use tanning beds, attitudes toward tanning and
      tanning bed use intentions. Structural equation modeling was performed to test
      the hypotheses. In general, results supported the proposed hypotheses and
      documented that sensation seeking is indirectly associated with tanning bed use
      intentions through the mediation of association with peers who use tanning beds
      and attitudes toward tanning. The article discusses theoretical and
      methodological implications of the findings demonstrating the pathways of
      influence of sensation seeking on tanning bed use intentions.

PMID- 19574407
TI  - Impact of bupropion and cognitive-behavioral treatment for depression on positive
      affect, negative affect, and urges to smoke during cessation treatment.
AB  - INTRODUCTION: Bupropion and cognitive-behavioral treatment (CBT) for depression
      have been used as components of treatments designed to alleviate affective
      disturbance during smoking cessation. Studies of treatment-related changes in
      precessation affect or urges to smoke are needed to evaluate the proposed
      mechanisms of these treatments. METHODS: The present report examines affective
      trajectories and urges to smoke prior to, on quit day, and after quitting in a
      sample of 524 smokers randomized to receive bupropion versus placebo and CBT
      versus standard smoking cessation CBT. RESULTS: Bupropion and/or CBT did not
      affect the observed decreases in positive affect and increases in negative affect
      prior to cessation. However, on quit day, observed levels of negative affect and
      urges to smoke were diminished significantly among individuals receiving
      bupropion. Decreases in positive affect prior to quitting, lower levels of
      positive affect, and increased levels of negative affect and urges to smoke on
      quit day were each related to higher risk of smoking lapse. Depression proneness
      was an independent predictor of lower positive affect and higher negative affect
      but did not moderate the effects of bupropion on outcomes. In mediational
      analyses, the effect of bupropion was accounted for in part by lower negative
      affect and urges to smoke on quit day. DISCUSSION: Results support the efficacy
      of bupropion in reducing relapse risk associated with urges to smoke and negative
      affect and suggest the need to better understand the role of low positive affect
      as a risk factor for early lapse.

PMID- 19574408
TI  - Quantitative determination of skin penetration of PEG-coated CdSe quantum dots in
      dermabraded but not intact SKH-1 hairless mouse skin.
AB  - Many cosmetics, sunscreens, and other consumer products are reported to contain
      nanoscale materials. The possible transdermal absorption of nanoscale materials
      and the long-term consequences of the absorption have not been determined. We
      used polyethylene glycol coated cadmium selenide (CdSe) core quantum dots (QD; 37
      nm diameter) to evaluate the penetration of nanoscale material into intact, tape
      stripped, acetone treated, or dermabraded mouse skin. QD were suspended in an oil
      in-water emulsion (approximately 9 microM) and the emulsion was applied at 2
      mg/cm(2) to mouse dorsal skin pretreated as follows: intact; tape stripped to
      remove the stratum corneum; acetone pretreated; dermabraded to remove stratum
      corneum and epidermis. QD penetration into the skin was monitored in sentinel
      organs (liver and regional draining lymph nodes) using inductively coupled plasma
      mass spectrometry analysis of cadmium (from the CdSe QD). No consistent cadmium
      elevation was detected in the sentinel organs of mice with intact, acetone
      pretreated, or tape-stripped skin at 24- and 48-h post-QD application; however,
      in dermabraded mice, cadmium elevations were detected in the lymph nodes and
      liver. QD accumulation (as cadmium) in the liver was approximately 2.0% of the
      applied dose. The passing of QD through the dermabraded skin was confirmed using
      confocal fluorescence microscopy. These results suggest that transdermal
      absorption of nanoscale materials depends on skin barrier quality, and that the
      lack of an epidermis provided access to QD penetration. Future dermal risk
      assessments of nanoscale materials should consider key barrier aspects of skin
      and its overall physiologic integrity.

PMID- 19574410
TI  - Multiplex PCR for rapid detection of genes encoding oxacillinases and metallo
      beta-lactamases in carbapenem-resistant Acinetobacter spp.

PMID- 19574409
TI  - Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen
      receptor alpha at human promoters.
AB  - Recent studies have shown that activated aryl hydrocarbon receptor (AHR) induced
      the recruitment of estrogen receptor-alpha (ERalpha) to AHR-regulated genes and
      that AHR is recruited to ERalpha-regulated genes. However, these findings were
      limited to a small number of well-characterized AHR- or ERalpha-responsive genes
      with little knowledge of what was occurring at other genomic regions. In this
      study, we showed using chromatin immunoprecipitation followed by hybridization to
      promoter focused microarrays (ChIP-chip) that 2,3,7,8-tetrachlorodibenzo-p-dioxin
      treatment significantly increased the overlap of genomic regions bound by both
      AHR and ERalpha. Conventional and sequential ChIPs confirmed the recruitment of
      AHR and ERalpha to many of the identified regions. Transcription factor binding
      site analysis revealed an overrepresentation of aryl hydrocarbon receptor
      response elements in regions bound by both AHR and ERalpha, suggesting that AHR
      was the important factor determining the recruitment of ERalpha to these regions.
      RNA interference-mediated knockdown of AHR confirmed its requirement for the
      recruitment of ERalpha to some, but not all, of the shared regions. Our findings
      demonstrate not only that dioxin induces the recruitment of ERalpha to AHR target
      genes but also that AHR is recruited to estrogen-responsive regions in a gene
      specific manner, suggesting that AHR utilizes both of these mechanisms to
      modulate estrogen-dependent signaling.

PMID- 19574411
TI  - Emergence of metallo-beta-lactamases in the Netherlands.

PMID- 19574412
TI  - Molecular characterization of extended-spectrum beta-lactamase-producing
      Escherichia coli isolates from chickens in Henan Province, China.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has spread
      rapidly worldwide and poses a serious threat to human and animal health. This
      study collected 51 non-replicate E. coli isolates from 14 different chicken farms
      in Henan Province in China from December 2007 to August 2008. The prevalence of
      ESBL-producing E. coli, molecular characterization of the ESBL-related bla genes,
      including bla(TEM), bla(SHV) and bla(CTX-M), and the susceptibilities of these
      bacteria to various antimicrobial agents were determined. Thirty-one of the 51
      isolates were positive for an ESBL phenotype and 29 of these isolates carried one
      or more bla genes. Twenty-two isolates harboured bla(TEM) genes and 15 isolates
      carried bla(CTX-M) genes (one CTX-M-14, three CTX-M-24 and 11 CTX-M-65). One
      isolate carried bla(TEM)(-57); the remaining bla(TEM) isolates carried bla(TEM-1)
      with one silent nucleotide base variation (T18C). We believe that this is the
      first study to report TEM-57 in E. coli isolates. All isolates harbouring bla(CTX
      M-24) and bla(CTX-M-14) and five of the bla(CTX-M-65) isolates also harboured the
      bla(TEM-1) gene. To our knowledge, this study is the first to describe detection
      of CTX-M-65-producing E. coli isolated from chickens. None of the isolates
      contained the bla(SHV) gene. Conjugation experiments demonstrated that bla(CTX-M)
      and bla(TEM) genes could be transferred to E. coli DH5 alpha. The results
      indicate that ESBL frequency has reached an alarming level in chicken isolates in
      China, with TEM-1 and CTX-M-65 enzymes being the two predominant beta-lactamases
      detected.

PMID- 19574413
TI  - Septic arthritis due to Roseomonas gilardii in an immunocompetent adolescent.
AB  - The genus Roseomonas comprises groups of slow-growing, Gram-negative
      coccobacilli, which only infrequently cause infection in humans. When identified,
      they are associated with immunocompromised adults, often causing bacteraemia. Due
      to their rarity, members of this genus can be overlooked or misidentified using
      automated laboratory identification systems. We report on an immunocompetent
      adolescent patient who developed septic arthritis due to Roseomonas gilardii
      following surgery for a sports injury. The isolate was initially misidentified as
      Bordetella bronchiseptica using the Vitek 2 system, but confirmed as R. gilardii
      based on 16S rRNA gene sequencing. To the best of our knowledge, this is the
      first case of a healthy paediatric patient with septic arthritis due to R.
      gilardii.

PMID- 19574414
TI  - Proton motive force-dependent efflux of tetracycline in clinical isolates of
      Helicobacter pylori.
AB  - The aim of this study was to evaluate the role of proton motive force (PMF)
      dependent efflux in resistance of Helicobacter pylori to tetracycline (Tet). Tet
      MIC was determined by agar dilution in the presence and absence of carbonyl
      cyanide m-chlorophenylhydrazone (CCCP), an inhibitor of PMF. Antibiotic
      accumulation was conducted in the presence or absence of CCCP and the
      fluorescence of the accumulated antibiotic was measured by spectrofluorometry. In
      the presence of CCCP, antibiotic accumulation was increased by 2-17-fold in 17/20
      Tet(r) isolates and by 3-10-fold in four of five high-level-resistant mutants.
      Correlation was observed between this increase and diminution of MIC with CCCP.
      PMF-dependent efflux mechanisms therefore appear to play an important role in the
      resistance of clinical isolates of H. pylori to Tet.

PMID- 19574416
TI  - Distribution of Escherichia coli F4 adhesion phenotypes in pigs of 15 Chinese and
      Western breeds and a White DurocxErhualian intercross.
AB  - Diarrhoea in newborn and weaned piglets is mainly caused by enterotoxigenic
      Escherichia coli (ETEC) with fimbriae F4. To investigate the prevalence of
      resistance to three fimbrial strains, F4ab, F4ac and F4ad, among Chinese
      indigenous pigs and Western commercial pigs introduced into China, we determined
      the ETEC F4 adhesion phenotypes in 292 pure-bred piglets from three Western
      commercial breeds and 12 Chinese indigenous breeds, and a total of 1093 adult
      pigs in a White DurocxErhualian intercross, by an in vitro microscopic adhesion
      assay. All the Tibet and Lantang pigs and a majority of the Erhualian and
      Rongchang pigs were resistant (nonadherent) to ETEC F4 whereas all the Laiwu pigs
      and most of the Jiangquhai and Tongcheng pigs were susceptible (adhesive) to at
      least one of the F4 strains. Yushan Black pigs were uniformly resistant to F4ab,
      and Jinhua pigs were predominantly resistant to F4ac. Susceptible and resistant
      animals were observed in the other breeds, indicating that diarrhoea caused by
      ETEC F4 could be prevalent in these breeds. This study confirmed the existence of
      eight previously reported F4 adhesion patterns, and supported the assumption that
      the three F4 receptors are encoded by distinct loci. Expression of the weakly
      adherent phenotype was observed in six pure-bred piglets and 90 adult F(2)/F(3)
      animals, and the inheritance of this phenotype and its correlation with
      susceptibility to disease are still not known.

PMID- 19574415
TI  - Two variants of staphylococcal cassette chromosome mec type IVA in community
      associated meticillin-resistant Staphylococcus aureus strains in South Korea.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) strains harbouring
      staphylococcal cassette chromosome mec (SCCmec) type IVA are known to be more
      prevalent in South Korea than in other countries. Variations in the SCCmec IVA
      structure have been identified, including in sequence type (ST) 1 and ST72
      strains. This study compared and investigated the genetic characteristics of two
      subtypes common in South Korea. Type IVA SCCmec of ST1 strains was characterized
      by type IV features with the linearized pUB110 at the junkyard (J) 3 region.
      However, that of ST72 strains carried a variant class B mec complex, ccrA2, with
      an identity of approximately 96 % and the linearized pUB110 at the J3 region. In
      SCCmec of ST72 strains, the organization of the class B variant and the J3 region
      may be more similar to that of type IA than to other types, but the ccr type and
      other J regions seemed to be derived from type IV. These genetic characteristics
      showed that type IVA appears to result from the dynamic genetic exchange and
      recombination of SCC DNA.

PMID- 19574417
TI  - Improving the biomarker pipeline to develop and evaluate cancer screening tests.
AB  - The biomarker pipeline to develop and evaluate cancer screening tests has three
      stages: identification of promising biomarkers for the early detection of cancer,
      initial evaluation of biomarkers for cancer screening, and definitive evaluation
      of biomarkers for cancer screening. Statistical and biological issues to improve
      this pipeline are discussed. Although various recommendations, such as
      identifying cases based on clinical symptoms, keeping biomarker tests simple, and
      adjusting for postscreening noise, have been made previously, they are not widely
      known. New recommendations include more frequent specimen collection to help
      identify promising biomarkers and the use of the paired availability design with
      interval cases (symptomatic cancers detected in the interval after screening) for
      initial evaluation of biomarkers for cancer screening.

PMID- 19574418
TI  - Associations between hepatitis B virus mutations and the risk of hepatocellular
      carcinoma: a meta-analysis.
AB  - BACKGROUND: The association between hepatitis B virus (HBV) mutations and
      hepatocarcinogenesis remains controversial because of conflicting data in the
      literature. We conducted a meta-analysis of case-control and cohort studies to
      examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore
      mutations in relation to the risk of hepatocellular carcinoma (HCC). METHODS: We
      searched databases for studies of these associations that were published in
      English or Chinese up to August 31, 2008. HBV mutation-specific odds ratios and
      relative risks were pooled by use of a random-effects model and stratified by
      potential confounders. All statistical tests were two-sided. RESULTS: Of the 43
      studies included in this meta-analysis, 40 used a case-control design. The 43
      studies evaluated a total of 11 582 HBV-infected participants, of whom 2801 had
      HCC. Statistically significant summary odds ratios of HCC were obtained for any
      PreS mutation (3.77, 95% confidence interval [CI] = 2.57 to 5.52), C1653T in
      EnhII (2.76, 95% CI = 2.09 to 3.64), T1753V (2.35, 95% CI = 1.63 to 3.40), and
      A1762T/G1764A in BCP (3.79, 95% CI = 2.71 to 5.29). PreS mutations were more
      strongly associated with an increased risk of HCC in subjects who were infected
      with HBV genotype C than in those who were infected with HBV genotype B, whereas
      the opposite was true for A1762T/G1764A. C1653T, T1753V, and A1762T/G1764A were
      more strongly associated with an increased risk of HCC in hepatitis B e antigen
      (HBeAg)-positive subjects than in HBeAg-negative subjects. PreS mutations,
      C1653T, T1753V, and A1762T/G1764A accumulated during the progression of chronic
      HBV infection from the asymptomatic carrier state to HCC (P(trend) < .001 for
      each mutation). PreS mutations, C1653T, C1653T + T1753V, and A1762T/G1764A-based
      combinations of mutations had specificities greater than 80% for the prediction
      of HCC. The precore mutations G1896A and C1858T were not associated with the risk
      of HCC, regardless of HBeAg status and HBV genotype. CONCLUSIONS: HBV PreS
      mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased
      risk of HCC. These mutations alone and in combination may be predictive for
      hepatocarcinogenesis.

PMID- 19574419
TI  - Adenosine A2B receptors are highly expressed on murine type II alveolar
      epithelial cells.
AB  - The adenosine A(2B) receptor (A(2B)R) has a wide tissue distribution that
      includes fibroblasts and endothelial and epithelial cells. The recent generation
      of an A(2B)R(-/-) mouse constructed with a beta-galactosidase (beta-gal) reporter
      gene under control of the endogenous promoter has provided a valuable tool to
      quantify A(2B)R promoter activity (29). To determine the sites of expression of
      the A(2B) receptor in the mouse lung, histological and flow cytometric analysis
      of beta-gal reporter gene expression in various lung cell populations was
      performed. The major site of A(2B)R promoter activity was found to be the type II
      alveolar epithelial cells (AECs), identified by coexpression of prosurfactant
      protein C, with relatively less expression in alveolar macrophages, bronchial
      epithelial cells, and cells of the vasculature. Highly purified type II AECs were
      prepared by fluorescence-activated sorting of enhanced green fluorescent protein
      (eGFP)-positive cells from transgenic mice expressing eGFP under control of the
      surfactant protein C promoter (21). The type II cells expressed 89-fold higher
      A(2B)R mRNA than pulmonary leukocytes, and the A(2B)R was shown to be functional,
      as treatment of purified type II AECs with the nonspecific adenosine receptor
      agonist 5'-N-ethylcarboxamidoadenosine (NECA) induced an increase in
      intracellular cAMP greater that the beta-adrenergic agonist isoproterenol that
      was inhibited completely following treatment by ATL-802, a novel, highly potent
      (K(i) = 8.6 nM), and selective (>900 fold over other adenosine receptor subtypes)
      antagonist of the mouse A(2B)R.

PMID- 19574420
TI  - 1alpha,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial
      mesenchymal interactions and inhibit lipofibroblast apoptosis.
AB  - Although alveolar wall thinning has been attributed to apoptosis of interstitial
      lung lipofibroblasts (LFs), the underlying molecular mechanism(s) remains
      unknown. Although the physiological vitamin D steroid hormone
      1alpha,25(OH)(2)D(3) (1,25D) has been suggested as a local paracrine/autocrine
      effector of fetal lung maturation and is known to affect fibroblast apoptosis,
      its effects on LF apoptosis are unknown. We determined the role of 1,25D and its
      metabolite, C-3-epimer (3-epi-1,25D), on LF and alveolar type II (ATII) cell
      differentiation, proliferation, and apoptosis. Embryonic day 19 Sprague-Dawley
      fetal rat lung LFs and ATII cells were treated with 1,25D or 3-epi-1,25D (1 x 10(
      10) to 1 x 10(-8) M) for 24 h, and cell proliferation, apoptosis, and
      differentiation were assessed. Both 1,25D and 3-epi-1,25D exhibited dose
      dependent increases in expression of the key homeostatic epithelial-mesenchymal
      differentiation markers, increased LF and ATII cell proliferation, and decreased
      apoptosis. Furthermore, rat pups administered 1,25D from postnatal days 0 to 14
      showed increased expressions of key LF and ATII cell differentiation markers,
      increased Bcl-2-to-Bax ratio as an index of decreased spontaneous alveolar LF and
      ATII cell apoptosis, increased alveolar count, and a paradoxical increase in
      septal thickness. We conclude that spatial- and temporal-specific actions of
      vitamin D play a critical role in perinatal lung maturation by stimulating key
      alveolar epithelial-mesenchymal interactions and by modulating LF
      proliferation/apoptosis. These data not only provide the biological rationale for
      the presence of an alveolar vitamin D paracrine system, but also provide the
      first integrated molecular mechanism for increased surfactant synthesis and
      alveolar septal thinning during perinatal lung maturation.

PMID- 19574421
TI  - PLAGL2 expression-induced lung epithelium damages at bronchiolar alveolar duct
      junction in emphysema: bNip3- and SP-C-associated cell death/injury activity.
AB  - Emphysema and bronchitis are major components of chronic obstructive pulmonary
      disease (COPD). Pleomorphic adenoma gene like-2 (PLAGL2), a zinc finger DNA
      binding protein, is a transcription factor of the surfactant protein C (SP-C)
      promoter. Using an inducible transgenic mouse model, PLAGL2 and SP-C were
      ectopically expressed in lung epithelial cells of terminal bronchiole including
      the bronchoalveolar duct junction (BADJ), where only few cells express both genes
      under normal conditions. Ectopic PLAGL2 was also expressed in alveolar type II
      cells of induced mice. The overexpression of PLAGL2 was associated with the
      development of air space enlargement in the distal airways of adult mice.
      Defective alveolar septa and degraded airway fragments were found in the lesions
      of emphysematous lungs, indicating chronic airway destruction. Female mice were
      particularly sensitive to the effects of PLAGL2 overexpression with more dramatic
      emphysematous changes compared with male mice. In addition, analysis of the
      respiratory system mechanics in the mice indicated that the induction of PLAGL2
      resulted in a significant increase in respiratory system compliance. Both TdT
      mediated dUTP nick end labeling (TUNEL) and caspase-3 analyses showed that
      apoptotic activity was increased in epithelial cells within the emphysematous
      lesions as well as at the BADJ. Our results indicate that increased cell injury
      and/or death could be caused directly by the upregulation of PLAGL2 downstream
      gene, bNip3, a preapoptotic molecule that dimerizes with Bcl-2, or indirectly by
      the aberrant expression of SP-C-induced endoplasmic reticulum stress in
      epithelial cells. Finally, increased expression of PLAGL2 in alveolar epithelial
      cells correlated with the development of emphysema in the lung of COPD patients.
      In summary, our data from both animal and human studies support a novel
      pathogenic role of PLAGL2 in pulmonary emphysema, a critical aspect of severe
      COPD.

PMID- 19574422
TI  - IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and
      maturation in preterm fetal lamb lung.
AB  - Preterm infants exposed to chorioamnionitis and preterm sheep fetuses exposed to
      intra-amniotic (IA) LPS have lung inflammation, increased IL-8 levels, and lung
      maturation. We tested the hypothesis that IL-8 signaling mediates IA LPS-induced
      lung inflammation and lung maturation. Two strategies were used: 1) we tested if
      IA injection of recombinant sheep IL-8 (rsIL-8) induced fetal inflammation and 2)
      if IL-8 signaling was blocked by a novel CXCR2 receptor blocker, nicotinanilide
      thioglycolate methyl ester (NTME). To test effects of IL-8 in the fetus, rsIL-8
      was given intravascularly (50 microg) at 124 +/- 1 day of gestation (term = 150
      days). A separate group of sheep was given IA rsIL-8 (100 microg) and delivered 5
      h to 7 days later at 124 +/- 1 day of gestation. After confirming efficacy of the
      CXCR2 inhibitor, effects of IL-8 blockade were tested by injecting fetal sheep
      intramuscularly with NTME (10 mg) before IA injection of Escherichia coli LPS (10
      mg). Sheep fetuses were delivered 1 or 7 days after injections at 124 +/- 1 day
      of gestation. IA rsIL-8 induced a modest fivefold increase in bronchoalveolar
      lavage (BAL) monocytes and neutrophils and increased lung monocyte hydrogen
      peroxide generation. However, rsIL-8 did not induce lung maturation.
      Intravascular rsIL-8 did not change fetal cardiovascular variables, blood pH, or
      blood leukocyte counts. Inhibition of CXCR2 decreased IA LPS-induced increases in
      BAL proteins at 1 day but not at 7 days. NTME did not significantly decrease IA
      LPS-induced BAL leukocyte influx and lung cytokine mRNA expression. Inhibition of
      CXCR2 did not change IA LPS-induced lung maturation. IL-8 signaling does not
      mediate LPS-induced lung inflammation and lung maturation.

PMID- 19574423
TI  - Mechanical stretch decreases FAK phosphorylation and reduces cell migration
      through loss of JIP3-induced JNK phosphorylation in airway epithelial cells.
AB  - JNK is a nonreceptor kinase involved in the early events that signal cell
      migration after injury. However, the linkage to early signals required to
      initiate the migration response to JNK has not been defined in airway epithelial
      cells, which exist in an environment subjected to cyclic mechanical strain (MS).
      The present studies demonstrate that the JNK/stress-activated protein kinase
      associated protein 1 (JSAP1; also termed JNK-interacting protein 3, JIP3), a
      scaffold factor for MAPK cascades that links JNK activation to focal adhesion
      kinase (FAK), are both associated and activated following mechanical injury in
      16HBE14o- human airway epithelial cells and that both FAK and JIP3
      phosphorylation seen after injury are decreased in cells subjected to cyclic MS.
      Overexpression of either wild-type (WT)-FAK or WT-JIP3 enhanced phosphorylation
      and kinase activation of JNK and reduced the inhibitory effect of cyclic MS.
      These results suggest that cyclic MS impairs signaling of cell migration after
      injury via a pathway that involves FAK-JIP3-JNK.

PMID- 19574425
TI  - Macrophages are alternatively activated in patients with endometriosis and
      required for growth and vascularization of lesions in a mouse model of disease.
AB  - The mechanisms that sustain endometrial tissues at ectopic sites in patients with
      endometriosis are poorly understood. Various leukocytes, including macrophages,
      infiltrate endometriotic lesions. In this study, we depleted mouse macrophages by
      means of either clodronate liposomes or monoclonal antibodies before the
      injection of syngeneic endometrial tissue. In the absence of macrophages, tissue
      fragments adhered and implanted into the peritoneal wall, but endometriotic
      lesions failed to organize and develop. When we depleted macrophages after the
      establishment of endometriotic lesions, blood vessels failed to reach the inner
      layers of the lesions, which stopped growing. Macrophages from patients with
      endometriosis and experimental mice, but not nonendometriotic patients who
      underwent surgery for uterine leiomyomas or control mice, expressed markers of
      alternative activation. These markers included high levels of scavenger
      receptors, CD163 and CD206, which are involved in both the scavenging of
      hemoglobin with iron transfer into macrophages and the silent clearance of
      inflammatory molecules. Macrophages in both inflammatory liquid and ectopic
      lesions were equally polarized, suggesting a critical role of environmental cues
      in the peritoneal cavity. Adoptively transferred, alternatively activated
      macrophages dramatically enhanced endometriotic lesion growth in mice.
      Inflammatory macrophages effectively protected mice from endometriosis.
      Therefore, endogenous macrophages involved in tissue remodeling appear as players
      in the natural history of endometriosis, required for effective vascularization
      and ectopic lesion growth.

PMID- 19574424
TI  - Investigation of the role of glypican 3 in liver regeneration and hepatocyte
      proliferation.
AB  - Glypicans are heparan sulfate proteoglycans that are bound to the cell surface by
      glycosylphosphatidylinositol. While six members of the glypican family are known
      in mammals, our study focused on glypican 3 (GPC3). Loss-of-function mutations of
      GPC3 result in the Simpson-Golabi-Behmel syndrome, an X-linked disorder
      characterized by pre- and postnatal liver and other organ overgrowth. GPC3 is
      overexpressed in human hepatocellular carcinoma; however, its role in normal
      liver regeneration and hepatocyte proliferation is unknown. Here we investigated
      the role of GPC3 in hepatocyte proliferation. GPC3 mRNA and protein levels begin
      to increase 2 days after hepatectomy with peak expression levels by day 5. In
      hepatocyte cultures, GPC3 reaches a plateau when hepatocyte proliferation
      decreases. In vitro studies using Morpholino oligonucleotides showed that
      blocking GPC3 expression promoted hepatocyte growth. Yeast two-hybrid assays
      revealed that GPC3 interacts with CD81, a member of the tetraspanin family that
      is reported to be involved in hepatitis C virus infection and cell proliferation.
      We found that CD81 levels also increased 2 days after partial hepatectomy and
      toward the end of regeneration. Immunofluorescence showed that CD81 and GPC3
      colocalize by 2 and 6 days after hepatectomy. Co-immunoprecipitation validated
      the interaction of GPC3 and CD81. Our results indicate that GPC3 may be a
      negative regulator of liver regeneration and hepatocyte proliferation, and that
      this regulation may involve CD81.

PMID- 19574426
TI  - Angiogenesis in platelet endothelial cell adhesion molecule-1-null mice.
AB  - Platelet endothelial cell adhesion molecule (PECAM)-1 has been previously
      implicated in endothelial cell migration; additionally, anti-PECAM-1 antibodies
      have been shown to inhibit in vivo angiogenesis. Studies were therefore performed
      with PECAM-1-null mice to further define the involvement of PECAM-1 in blood
      vessel formation. Vascularization of subcutaneous Matrigel implants as well as
      tumor angiogenesis were both inhibited in PECAM-1-null mice. Reciprocal bone
      marrow transplants that involved both wild-type and PECAM-1-deficient mice
      revealed that the impaired angiogenic response resulted from a loss of
      endothelial, but not leukocyte, PECAM-1. In vitro wound migration and single-cell
      motility by PECAM-1-null endothelial cells were also compromised. In addition,
      filopodia formation, a feature of motile cells, was inhibited in PECAM-1-null
      endothelial cells as well as in human endothelial cells treated with either anti
      PECAM-1 antibody or PECAM-1 siRNA. Furthermore, the expression of PECAM-1
      promoted filopodia formation and increased the protein expression levels of
      Cdc42, a Rho GTPase that is known to promote the formation of filopodia. In the
      developing retinal vasculature, numerous, long filamentous filopodia, emanating
      from endothelial cells at the tips of angiogenic sprouts, were observed in wild
      type animals, but to a lesser extent in the PECAM-1-null mice. Together, these
      data further establish the involvement of endothelial PECAM-1 in angiogenesis and
      suggest that, in vivo, PECAM-1 may stimulate endothelial cell motility by
      promoting the formation of filopodia.

PMID- 19574427
TI  - Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide
      hormone receptors.
AB  - Through alternative splicing, multiple different transcripts can be generated
      from a single gene. Alternative splicing represents an important molecular
      mechanism of gene regulation in physiological processes such as developmental
      programming as well as in disease. In cancer, splicing is significantly altered.
      Tumors express a different collection of alternative spliceoforms than normal
      tissues. Many tumor-associated splice variants arise from genes with an
      established role in carcinogenesis or tumor progression, and their functions can
      be oncogenic. This raises the possibility that products of alternative splicing
      play a pathogenic role in cancer. Moreover, cancer-associated spliceoforms
      represent potential diagnostic biomarkers and therapeutic targets. G protein
      coupled peptide hormone receptors provide a good illustration of alternative
      splicing in cancer. The wild-type forms of these receptors have long been known
      to be expressed in cancer and to modulate tumor cell functions. They are also
      recognized as attractive clinical targets. Recently, splice variants of these
      receptors have been increasingly identified in various types of cancer. In
      particular, alternative cholecystokinin type 2, secretin, and growth hormone
      releasing hormone receptor spliceoforms are expressed in tumors. Peptide hormone
      receptor splice variants can fundamentally differ from their wild-type receptor
      counterparts in pharmacological and functional characteristics, in their
      distribution in normal and malignant tissues, and in their potential use for
      clinical applications.

PMID- 19574428
TI  - CD19, a response regulator of B lymphocytes, regulates wound healing through
      hyaluronan-induced TLR4 signaling.
AB  - Immune cells are critical to the wound-healing process, through both cytokine and
      growth factor secretion. Although previous studies have revealed that B cells are
      present within wound tissue, little is known about the role of B cells in wound
      healing. To clarify this, we investigated cutaneous wound healing in mice either
      lacking or overexpressing CD19, a critical positive-response regulator of B
      cells. CD19 deficiency inhibited wound healing, infiltration of neutrophils and
      macrophages, and cytokine expression, including basic and acidic fibroblast
      growth factor, interleukin-6, platelet-derived growth factor, and transforming
      growth factor-beta. By contrast, CD19 overexpression enhanced wound healing and
      cytokine expression. Hyaluronan (HA), an endogenous ligand for toll-like receptor
      (TLR)-4, stimulated B cells, which infiltrates into wounds to produce interleukin
      6 and transforming growth factor-beta through TLR4 in a CD19-dependent manner.
      CD19 expression regulated TLR4 signaling through p38 activation. HA accumulation
      was increased in injured skin tissue relative to normal skin, and exogenous
      application of HA promoted wound repair in wild-type but not CD19-deficient mice,
      suggesting that the beneficial effects of HA to the wound-healing process are
      CD19-dependent. Collectively, these results suggest that increased HA
      accumulation in injured skin induces cytokine production by stimulating B cells
      through TLR4 in a CD19-dependent manner. Thus, this study is the first to reveal
      a critical role of B cells and novel mechanisms in wound healing.

PMID- 19574429
TI  - Diabetic albuminuria is due to a small fraction of nephrons distinguished by
      albumin-stained tubules and glomerular adhesions.
AB  - OVE26 diabetic mice develop severe albuminuria. Immunohistochemical analysis
      revealed a pattern of intense albumin staining in a small subset of OVE26
      tubules. Immunostaining was strikingly heterogeneous; some tubules stained
      intensely for albumin, but most tubules had weak or no staining. Serial
      sectioning showed that staining patterns were distinctive for each nephron.
      Electron microscopy revealed that albumin accumulated in villi and at the base of
      the brush border. Tubule cell injury, as shown by loss of villi, tubule dilation,
      and cellular protrusions into the tubule lumen, was unambiguously associated with
      albumin staining. Examination of albumin staining of proteinuric human kidneys
      also showed a heterogeneous pattern of staining. Analysis of OVE26 serial
      sections indicated that all glomeruli connected to albumin-positive tubules were
      identified by albumin-stained lesions in the tuft that adhered to Bowman's
      capsule, implicating this as a critical feature of heavy albumin leakage. These
      results indicate that albumin accumulation provides a marker of damaged nephrons,
      and confirm that albumin leakage produces significant tubular damage. This study
      shows that that formation of sclerotic glomerular adhesions is a critical step
      leading to severe albuminuria.

PMID- 19574430
TI  - Expression of integrin alpha6beta1 enhances tumorigenesis in glioma cells.
AB  - The integrin alpha6beta1 and its main ligand laminin-111 are overexpressed in
      glioblastoma, as compared with normal brain tissue, suggesting they may be
      involved in glioblastoma malignancy. To address this question, we stably
      expressed the alpha6 integrin subunit in the U87 cell line via retroviral
      mediated gene transfer. We show that cell surface expression of the alpha6beta1
      integrin led to dramatic changes in tumor U87 cell behavior, both in vitro and in
      vivo. Nude mice receiving either subcutaneous or intracerebral inoculation of
      alpha6beta1-expressing cells developed substantially more voluminous tumors than
      mice injected with control cells. The difference in tumor growth was associated
      with a marked increase in vascularization in response to alpha6beta1 integrin
      expression and may also be related to changes in the balance between cell
      proliferation and survival. Indeed, expression of alpha6beta1 enhanced
      proliferation and decreased apoptosis of U87 cells both in the tumor and in
      vitro. Additionally, we demonstrate that alpha6beta1 is implicated in
      glioblastoma cell migration and invasion and that laminin-111 might mediate
      dissemination of alpha6beta1-positive cells in vivo. Our results highlight for
      the first time the considerable role of the integrin alpha6beta1 in glioma
      progression.

PMID- 19574431
TI  - Plasminogen activator inhibitor type 1 up-regulation is associated with skeletal
      muscle atrophy and associated fibrosis.
AB  - Muscle wasting remains a feature of many diseases and is counteracted by anabolic
      supplementation or exercise. Persisting atrophy-inducing conditions can be
      complicated by skeletal muscle fibrosis, which leads to functional impairment.
      Identification of early mechanisms that initiate atrophy-induced fibrosis may
      reveal novel targets for therapy or diagnosis. Therefore, we investigated changes
      in the expression of genes involved in extracellular matrix homeostasis during
      glucocorticoid-induced atrophy of myotubes and compared them with insulin-like
      growth factor-1-induced hypertrophy. Obtained results were verified in rat
      gastrocnemius muscle that was exposed to microgravity by space flight for 2
      weeks. Myostatin and atrogin-1 mRNA levels reflected the magnitude of atrophy.
      Despite differential induction of these negative muscle mass regulators, no major
      changes in matrix metalloproteinases-2, -9, and -14 mRNAs or their physiological
      inhibitors could be detected in either atrophy model. In contrast, transcript
      levels of plasminogen activator inhibitor type 1 (PAI-1) was dramatically
      increased in atrophic myotubes and microgravity-exposed rat gastrocnemius muscle,
      while plasminogen activators remained unaltered. In contrast to atrophy, no
      increase in PAI-1 mRNA levels could be detected in rat hindlimb that was
      electrically stimulated for 21 days. Furthermore, a strong increase in PAI-1 mRNA
      levels was identified in skeletal muscle of patients with neurogenic muscle
      atrophy. Our study suggests that increased PAI-1 expression in atrophic skeletal
      muscle may lead to muscle fibrosis by reducing plasmin generation.

PMID- 19574432
TI  - Doxycycline treatment decreases morbidity and mortality of murine
      neurocysticercosis: evidence for reduction of apoptosis and matrix
      metalloproteinase activity.
AB  - Murine neurocysticercosis is a parasitic infection transmitted through the direct
      ingestion of Taenia solium eggs, which differentially disrupts the barriers that
      protect the microenvironment of the central nervous system. Among the host
      factors that are involved in this response, matrix metalloproteinases (MMPs) have
      been recently described as important players. Doxycycline is a commonly
      prescribed antimicrobial drug that acts as an anti-inflammatory agent with broad
      inhibitory properties against MMPs. In this study, we examined the effects of
      doxycycline treatment in a murine model of neurocysticercosis. Animals treated
      with doxycycline exhibited reduced morbidity and mortality throughout the course
      of infection. Although similar levels of leukocyte infiltration were observed
      with both treatment regimens, doxycycline appeared to provide improved conditions
      for host survival, as reduced levels of apoptosis were detected among infiltrates
      as well as in neurons. As an established MMP blocker, doxycycline reduced the
      degradation of junctional complex proteins in parenchymal vessels. In addition,
      doxycycline treatment was associated with an overall reduction in the expression
      and activity of MMPs, particularly in areas of leukocyte infiltration. These
      results indicate that a broad-range inhibitor of MMPs promotes host survival and
      suggest the potential of doxycycline as a therapeutic agent for the control of
      inflammatory responses associated with neurocysticercosis.

PMID- 19574433
TI  - Development of arterial blood supply in experimental liver metastases.
AB  - In this study, we present a mechanism for the development of arterial blood
      supply in experimental liver metastases. To analyze the arterialization process
      of experimental liver metastases, we elucidated a few key questions regarding the
      blood supply of hepatic lobules in mice. The microvasculature of the mouse liver
      is characterized by numerous arterioportal anastomoses and arterial terminations
      at the base of the lobules. These terminations supply one hepatic
      microcirculatory subunit per lobule, which we call an arterial hepatic
      microcirculatory subunit (aHMS). The process of arterialization can be divided
      into the following steps: 1) distortion of the aHMS by metastasis; 2) initial
      fusion of the sinusoids of the aHMS at the tumor parenchyma interface; 3) fusion
      of the sinusoids located at the base of the aHMSs, which leads to the disruption
      of the vascular sphincter (burst pipe); 4) incorporation of the dilated artery
      and the fused sinusoids into the tumor; and 5) further development of the tumor
      vasculature (arterial tree) by proliferation, remodeling, and continuous
      incorporation of fused sinusoids at the tumor-parenchyma interface. This process
      leads to the inevitable arterialization of liver metastases above the 2000- to
      2500-mum size, regardless of the origin and growth pattern of the tumor.

PMID- 19574435
TI  - Identification and characterization of maize and barley Lsi2-like silicon efflux
      transporters reveals a distinct silicon uptake system from that in rice.
AB  - Silicon (Si) uptake has been extensively examined in rice (Oryza sativa), but it
      is poorly understood in other gramineous crops. We identified Low Silicon Rice 2
      (Lsi2)-like Si efflux transporters from two important gramineous crops: maize
      (Zea mays) and barley (Hordeum vulgare). Both maize and barley Lsi2 expressed in
      Xenopus laevis oocytes showed Si efflux transport activity. Furthermore, barley
      Lsi2 was able to recover Si uptake in a rice mutant defective in Si efflux. Maize
      and barley Lsi2 were only expressed in the roots. Expression of maize and barley
      Lsi2 was downregulated in response to exogenously applied Si. Moreover, there was
      a significant positive correlation between the ability of roots to absorb Si and
      the expression levels of Lsi2 in eight barley cultivars, suggesting that Lsi2 is
      a key Si transporter in barley. Immunostaining showed that maize and barley Lsi2
      localized only at the endodermis, with no polarity. Protein gel blot analysis
      indicated that maize and barley Lsi2 localized on the plasma membrane. The unique
      features of maize and barley Si influx and efflux transporters, including their
      cell-type specificity and the lack of polarity of their localization in Lsi2,
      indicate that these crops have a different Si uptake system from that in rice.

PMID- 19574436
TI  - The maize transcription factor myb-related protein-1 is a key regulator of the
      differentiation of transfer cells.
AB  - Transfer cells are highly modified plant cells specialized in the transport of
      solutes. They differentiate at many plant exchange surfaces, including phloem
      loading and unloading zones such as those present in the sink organs and seeds.
      In maize (Zea mays) seeds, transfer cells are located at the base of the
      endosperm. It is currently unknown how apical-basal polarity is established or
      why the peripheral cells at the base of the endosperm differentiate into transfer
      instead of aleurone cells. Here, we show that in epidermal cells committed to
      develop into aleurone cells, the ectopic expression of the transfer cell-specific
      transcriptional activator Myb-Related Protein-1 (MRP-1) is sufficient to
      temporarily transform them into transfer cells. These transformed cells acquire
      distinct transfer cell features, such as cell wall ingrowths and an elongated
      shape. In addition, they express a number of MRP-1 target genes presumably
      involved in defense. We also show that the expression of MRP-1 is needed to
      maintain the transfer cell phenotype. Later in development, an observed reduction
      in the ectopic expression of MRP-1 was followed by the reversion of the
      transformed cells, which then acquire aleurone cell features.

PMID- 19574438
TI  - Selective changes in GABAA receptor subtypes in white matter neurons of patients
      with focal epilepsy.
AB  - Mapping the distribution of GABAA receptor subtypes represents a promising
      approach to characterize alterations in cortical circuitry associated with
      neurological disorders. We previously reported subtype-selective changes in GABAA
      receptor expression in the grey matter of patients with focal epilepsy. In the
      present follow-up study, we focused on the subcortical white matter in the same
      tissue specimens obtained at surgery from 9 patients with temporal lobe epilepsy
      (TLE) and hippocampal sclerosis, 12 patients with TLE associated with neocortical
      lesions and 5 patients with frontal lobe epilepsy; post-mortem tissue from 4
      subjects served as controls. The subunit composition and distribution of three
      major GABAA receptor subtypes were determined immunohistochemically with subunit
      specific antibodies. In all cases, a majority of neurons in the white matter was
      distinctly labelled, allowing detailed visualization of their dendritic
      arborization and revealing a differential, cell type-specific expression pattern
      of alpha-subunit variants. In controls, alpha1-subunit staining was most
      prominent, displaying a gradient that decreased with depth, in parallel with the
      density of NeuN-positive cells. Subsets of pyramidal cells were alpha3-subunit
      positive, and alpha2-subunit-labelled neurons were rare. In 19 of the 26 patients
      with focal epilepsy, no changes were detected as compared with controls. In five
      patients with TLE, striking changes in the dendritic arborization of a subset of
      white matter neurons were seen with the alpha1-subunit antibody. In two further
      patients with TLE, we observed a disorganized dendritic network immuno-positive
      for the alpha1-subunit, cell clusters selectively expressing the alpha2-subunit
      and small neuronal aggregates that expressed all subunits and appeared to connect
      to neighbouring white matter neurons. All seven patients with anomalies in the
      white matter had a selective reduction in alpha3-containing GABAA receptors in
      the superficial layers of the grey matter. These results demonstrate a distinct
      organization of GABAA receptors in human white matter neurons, consistent with an
      inhibitory network that is likely to be integrated functionally with the
      overlying grey matter. The altered dendritic morphology and changes in GABAA
      receptor expression in the white matter of a subset of patients with focal
      epilepsy are suggestive for a rewiring of neuronal circuits.

PMID- 19574434
TI  - What has natural variation taught us about plant development, physiology, and
      adaptation?
AB  - Nearly 100 genes and functional polymorphisms underlying natural variation in
      plant development and physiology have been identified. In crop plants, these
      include genes involved in domestication traits, such as those related to plant
      architecture, fruit and seed structure and morphology, as well as yield and
      quality traits improved by subsequent crop breeding. In wild plants, comparable
      traits have been dissected mainly in Arabidopsis thaliana. In this review, we
      discuss the major contributions of the analysis of natural variation to our
      understanding of plant development and physiology, focusing in particular on the
      timing of germination and flowering, plant growth and morphology, primary
      metabolism, and mineral accumulation. Overall, functional polymorphisms appear in
      all types of genes and gene regions, and they may have multiple mutational
      causes. However, understanding this diversity in relation to adaptation and
      environmental variation is a challenge for which tools are now available.

PMID- 19574437
TI  - Posttranslational elevation of cell wall invertase activity by silencing its
      inhibitor in tomato delays leaf senescence and increases seed weight and fruit
      hexose level.
AB  - Invertase plays multiple pivotal roles in plant development. Thus, its activity
      must be tightly regulated in vivo. Emerging evidence suggests that a group of
      small proteins that inhibit invertase activity in vitro appears to exist in a
      wide variety of plants. However, little is known regarding their roles in planta.
      Here, we examined the function of INVINH1, a putative invertase inhibitor, in
      tomato (Solanum lycopersicum). Expression of a INVINH1:green fluorescent protein
      fusion revealed its apoplasmic localization. Ectopic overexpression of INVINH1 in
      Arabidopsis thaliana specifically reduced cell wall invertase activity. By
      contrast, silencing its expression in tomato significantly increased the activity
      of cell wall invertase without altering activities of cytoplasmic and vacuolar
      invertases. Elevation of cell wall invertase activity in RNA interference
      transgenic tomato led to (1) a prolonged leaf life span involving in a blockage
      of abscisic acid-induced senescence and (2) an increase in seed weight and fruit
      hexose level, which is likely achieved through enhanced sucrose hydrolysis in the
      apoplasm of the fruit vasculature. This assertion is based on (1) coexpression of
      INVINH1 and a fruit-specific cell wall invertase Lin5 in phloem parenchyma cells
      of young fruit, including the placenta regions connecting developing seeds; (2) a
      physical interaction between INVINH1 and Lin5 in vivo; and (3) a symplasmic
      discontinuity at the interface between placenta and seeds. Together, the results
      demonstrate that INVINH1 encodes a protein that specifically inhibits the
      activity of cell wall invertase and regulates leaf senescence and seed and fruit
      development in tomato by limiting the invertase activity in planta.

PMID- 19574439
TI  - Age and albumin D site-binding protein control tissue plasminogen activator
      levels: neurotoxic impact.
AB  - Recombinant tissue-type plasminogen activator (tPA) is the fibrinolytic drug of
      choice to treat stroke patients. However, a growing body of evidence indicates
      that besides its beneficial thrombolytic role, tPA can also have a deleterious
      effect on the ischaemic brain. Although ageing influences stroke incidence,
      complications and outcome, age-dependent relationships between endogenous tPA and
      stroke injuries have not been investigated yet. Here, we report that ageing is
      associated with a selective lowering of brain tPA expression in the murine brain.
      Moreover, our results show that albumin D site-binding protein (DBP) as a key age
      associated regulator of the neuronal transcription of tPA. Additionally,
      inhibition of DBP-mediated tPA expression confers in vitro neuroprotection.
      Accordingly, reduced levels of tPA in old mice are associated with smaller
      excitotoxic/ischaemic injuries and protection of the permeability of the
      neurovascular unit during cerebral ischaemia. Likewise, we provide
      neuroradiological evidence indicating the existence of an inverse relationship
      between age and the volume of the ischaemic lesion in patients with acute
      ischaemic stroke. Together, these results indicate that the relationship among
      DBP, tPA and ageing play an important role in the outcome of cerebral ischaemia.

PMID- 19574440
TI  - Autism is characterized by dorsal anterior cingulate hyperactivation during
      social target detection.
AB  - Though the functional neural correlates of impaired cognitive control and social
      dysfunction in autism spectrum disorders (ASD) have been delineated, brain
      regions implicated in poor cognitive control of social information is a novel
      area of autism research. We recently reported in a non-clinical sample that
      detection of 'social oddball' targets activated a portion of the dorsal anterior
      cingulate gyrus and the supracalcarine cortex (Dichter, Felder, Bodfish, Sikich,
      and Belger, 2009). In the present investigation, we report functional magnetic
      resonance imaging results from individuals with ASD who completed the same social
      oddball task. Between-group comparisons revealed generally greater activation in
      the ASD group to both social and non-social targets. When responses to social and
      non-social targets were contrasted, the ASD group showed relatively greater
      activation in the right and middle inferior frontal gyri and a region in
      dorsomedial prefrontal cortex that abuts the dorsal anterior cingulate
      (Brodmann's Area 32). Further, dorsal anterior cingulate activation to social
      targets predicted the severity of social impairments in a subset of the ASD
      sample. These data suggest that the dorsal anterior cingulate mediates social
      target detection in neurotypical individuals and is implicated in deficits of
      cognitive control of social information in ASD.

PMID- 19574441
TI  - [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory
      response evaluation.
AB  - RATIONALE: Few noninvasive biomarkers for pulmonary inflammation are currently
      available that can assess the lung-specific response to antiinflammatory
      treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET)
      is a promising new method that can be used to quantify pulmonary neutrophilic
      inflammation. OBJECTIVES: To evaluate the ability of FDG-PET to measure the
      pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase
      inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human
      model of experimentally-induced lung inflammation. METHODS: Eighteen healthy
      volunteers were randomized to receive placebo, lovastatin, or rhAPC before
      intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed
      before and after endotoxin instillation. The rate of [(18)F]FDG uptake was
      calculated as the influx constant K(i) by Patlak graphical analysis.
      Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations
      for correlation with the PET imaging results. MEASUREMENTS AND MAIN RESULTS:
      There was a statistically significant decrease in K(i) in the lovastatin-treated
      group that was not seen in the placebo-treated group, suggesting attenuation of
      inflammation by lovastatin treatment despite a small decrease in BAL total
      leukocyte and neutrophil counts that was not statistically significant. No
      significant decrease in K(i) was observed in the rhAPC-treated group, correlating
      with a lack of change in BAL parameters and indicating no significant
      antiinflammatory effect with rhAPC. CONCLUSIONS: FDG-PET imaging is a sensitive
      method for quantifying the lung-specific response to antiinflammatory therapies
      and may serve as an attractive platform for assessing the efficacy of novel
      antiinflammatory therapies at early phases in the drug development process.
      Clinical trial registered with www.clinicaltrials.gov (NCT00741013).

PMID- 19574442
TI  - Spirometry centile charts for young Caucasian children: the Asthma UK
      Collaborative Initiative.
AB  - RATIONALE: Advances in spirometry measurement techniques have made it possible to
      obtain measurements in children as young as 3 years of age; however, in practice,
      application remains limited by the lack of appropriate reference data for young
      children, which are often based on limited population-specific samples.
      OBJECTIVES: We aimed to build on previous models by collating existing reference
      data in young children (aged 3-7 yr), to produce updated prediction equations
      that span the preschool years and that are also linked to established reference
      equations for older children and adults. METHODS: The Asthma UK Collaborative
      Initiative was established to collate lung function data from healthy young
      children aged 3 to 7 years. Collaborators included researchers with access to
      pulmonary function test data in healthy preschool children. Spirometry centiles
      were created using the LMS (lambda, micro, sigma) method and extend previously
      published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS: The
      Asthma UK centile charts for spirometry are based on the largest sample of
      healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers
      across 11 countries and provide a continuous reference with a smooth transition
      into adolescence and adulthood. These equations improve existing pediatric
      equations by considering the between-subject variability to define a more
      appropriate age-dependent lower limit of normal. The collated data set reflects a
      variety of equipment, measurement protocols, and population characteristics and
      may be generalizable across different populations. CONCLUSIONS: We present
      prediction equations for spirometry for preschool children and provide a
      foundation that will facilitate continued updating.

PMID- 19574443
TI  - Deletion of Pten expands lung epithelial progenitor pools and confers resistance
      to airway injury.
AB  - RATIONALE: Pten is a tumor-suppressor gene involved in stem cell homeostasis and
      tumorigenesis. In mouse, Pten expression is ubiquitous and begins as early as 7
      days of gestation. Pten(-/-) mouse embryos die early during gestation indicating
      a critical role for Pten in embryonic development. OBJECTIVES: To test the role
      of Pten in lung development and injury. METHODS: We conditionally deleted Pten
      throughout the lung epithelium by crossing Pten(flox/flox) with Nkx2.1-cre driver
      mice. The resulting Pten(Nkx2.1-cre) mutants were analyzed for lung defects and
      response to injury. MEASUREMENTS AND MAIN RESULTS: Pten(Nkx2.1-cre) embryonic
      lungs showed airway epithelial hyperplasia with no branching abnormalities. In
      adult mice, Pten(Nkx2.1-cre) lungs exhibit increased progenitor cell pools
      composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine
      cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar
      duct junctions. Pten deletion affected differentiation of various lung epithelial
      cell lineages, with a decreased number of terminally differentiated cells. Over
      time, Pten(Nxk2.1-cre) epithelial cells residing in the bronchioalveolar duct
      junctions underwent proliferation and formed uniform masses, supporting the
      concept that the cells residing in this distal niche may also be the source of
      procarcinogenic stem cells. Finally, increased progenitor cells in all the lung
      compartments conferred an overall selective advantage to naphthalene injury
      compared with wild-type control mice. CONCLUSIONS: Pten has a pivotal role in
      lung stem cell homeostasis, cell differentiation, and consequently resistance to
      lung injury.

PMID- 19574444
TI  - Circulating endothelial progenitor cells in preterm infants with bronchopulmonary
      dysplasia.
AB  - RATIONALE: The new form of bronchopulmonary dysplasia (BPD) is characterized by
      lung immaturity with disrupted alveolar and capillary development after extremely
      premature birth, but the mechanism of impaired lung vascular formation is still
      not completely understood. OBJECTIVES: We tested the hypothesis that reduced
      numbers of circulating endothelial progenitor cells at birth are associated with
      the development of BPD. METHODS: We studied ninety-eight preterm infants with
      gestational age of less than 32 weeks or a birth weight less than 1,500 g.
      Endothelial colony-forming cells (ECFCs) were assessed by clonogenic analysis in
      infants for whom cord blood was available. The proportion of circulating
      endothelial and hematopoietic cells was measured by flow cytometry at birth, at
      48 hours, and at 7 days of life. MEASUREMENTS AND MAIN RESULTS: ECFCs in cord
      blood were lower in infants who later developed BPD (median [range]: 0.00 [0.00
      0.48] vs. 2.00 [0.00-21.87]; P = 0.002). ECFCs decreased with decreasing
      gestational age (r = 0.41; P = 0.02), but even at extremely low gestational ages,
      infants with higher numbers of ECFCs were protected from BPD. The endothelial and
      hematopoietic cell subsets studied by flow cytometry were comparable in infants
      with and without BPD and rapidly decreased after birth. CONCLUSIONS: ECFCs are
      low at extremely low gestational ages and increase during gestation; extremely
      preterm infants who display lower numbers at birth have an increased risk of
      developing BPD. Our findings suggest that decreased ECFCs following extremely
      preterm birth may be associated with the risk for developing lung vascular
      immaturity characteristic of new BPD.

PMID- 19574446
TI  - Endogenous parathyroid hormone-related protein regulates the expression of PTH
      type 1 receptor and proliferation of vascular smooth muscle cells.
AB  - The PTH type 1 receptor (PTH1R) and PTHrP are expressed in vessels, where they
      contribute to regulating vascular smooth muscle cell (VSMC) function. Elevated
      PTHrP levels in VSMC are often associated with hyperplasia. In contrast,
      exogenous PTHrP, acting through the PTH1R, inhibits VSMC proliferation. In this
      study, we investigated the regulation of PTH1R expression by endogenous PTHrP and
      the associated effects on VSMC proliferation. Blocking binding of secreted PTHrP
      fragments to the PTH1R by treatment with either an antagonist or an antibody
      against PTHrP, and inhibition of PTHrP expression by small interfering RNA
      significantly increased PTH1R expression. Interestingly, treatment of the cells
      with a PTHrP analog (Bpa(1)-PTHrP) that activates the PTH1R without inducing its
      internalization had the same effect on receptor expression. To examine the
      association between receptor expression and the antiproliferative effect of N
      terminal fragments of PTHrP, VSMC were treated with exogenous PTHrP (1-36)
      acutely and chronically to induce receptor down-regulation. Stimulation of VSMC
      with exogenous PTHrP (1-36) significantly reduced cell proliferation during the
      first 18 h of treatment but was no longer effective after 3 d, a time when PTH1R
      was down-regulated. In contrast, treatment with the noninternalizing agonist
      Bpa(1)-PTHrP strongly inhibited cell proliferation at all time points. In
      conclusion, our study show that PTHrP, after its intracellular processing and
      secretion, promotes down-regulation of the PTH1R in VSMC, thereby regulating cell
      proliferation in an auto/paracrine fashion. This regulatory mechanism may have
      important implication during vascular remodeling, in particular in the
      development of neointima after arterial injury, where PTHrP overexpression
      occurs.

PMID- 19574445
TI  - The transcriptional response of the islet to pregnancy in mice.
AB  - The inability of the ss-cell to meet the demand for insulin brought about by
      insulin resistance leads to type 2 diabetes. In adults, ss-cell replication is
      one of the mechanisms thought to cause the expansion of ss-cell mass. Efforts to
      treat diabetes require knowledge of the pathways that drive facultative ss-cell
      proliferation in vivo. A robust physiological stimulus of ss-cell expansion is
      pregnancy and identifying the mechanisms underlying this stimulus may provide
      therapeutic leads for the treatment of type 2 diabetes. The peak in ss-cell
      proliferation during pregnancy occurs on d 14.5 of gestation in mice. Using
      advanced genomic approaches, we globally characterize the gene expression
      signature of pancreatic islets on d 14.5 of gestation during pregnancy. We
      identify a total of 1907 genes as differentially expressed in the islet during
      pregnancy. The islet's ability to compensate for relative insulin deficiency
      during metabolic stress is associated with the induction of both proliferative
      and survival pathways. A comparison of the genes induced in three different
      models of islet expansion suggests that diverse mechanisms can be recruited to
      expand islet mass. The identification of many novel genes involved in islet
      expansion during pregnancy provides an important resource for diabetes
      researchers to further investigate how these factors contribute to the
      maintenance of not only islet mass, but ultimately ss-cell mass.

PMID- 19574447
TI  - Maternal diabetes causes mitochondrial dysfunction and meiotic defects in murine
      oocytes.
AB  - The adverse effects of maternal diabetes on embryo development and pregnancy
      outcomes have recently been shown to occur as early as the one-cell zygote stage.
      The hypothesis of this study was that maternally inherited mitochondria in
      oocytes from diabetic mice are abnormal and thus responsible in part for this
      latency of developmental compromise. In ovulated oocytes from diabetic mice,
      transmission electron microscopy revealed an alteration in mitochondrial
      ultrastructure, and the quantitative analysis of mitochondrial DNA copy number
      demonstrated an increase. The levels of ATP and tricarboxylic acid cycle
      metabolites in diabetic oocytes were markedly reduced compared with controls,
      suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of
      mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore,
      oocytes from diabetic mice displayed a higher frequency of spindle defects and
      chromosome misalignment in meiosis, resulting in increased aneuploidy rates in
      ovulated oocytes. Collectively, our results suggest that maternal diabetes
      results in oocyte defects that are transmitted to the fetus by two routes: first,
      meiotic spindle and chromatin defects result in nondisjunction leading to
      embryonic aneuploidy; second, structural and functional abnormalities of oocyte
      mitochondria, through maternal transmission, provide the embryo with a
      dysfunctional complement of mitochondria that may be propagated during
      embryogenesis.

PMID- 19574448
TI  - DNA binding by estrogen receptor-alpha is essential for the transcriptional
      response to estrogen in the liver and the uterus.
AB  - The majority of the biological effects of estrogens in the reproductive tract are
      mediated by estrogen receptor (ER)alpha, which regulates transcription by several
      mechanisms. Because the tissue-specific effects of some ERalpha ligands may be
      caused by tissue-specific transcriptional mechanisms of ERalpha, we aimed to
      identify the contribution of DNA recognition to these mechanisms in two
      clinically important target organs, namely uterus and liver. We used a genetic
      mouse model that dissects DNA binding-dependent vs. independent transcriptional
      regulation elicited by ERalpha. The EAAE mutant harbors amino acid exchanges at
      four positions of the DNA-binding domain (DBD) of ERalpha. This construct was
      knocked in the ERalpha gene locus to produce ERalpha((EAAE/EAAE)) mice devoid of
      a functional ERalpha DBD. The phenotype of the ERalpha((EAAE/EAAE)) mice
      resembles the general loss-of-function phenotype of alphaER knockout mutant mice
      with hypoplastic uteri, hemorrhagic ovaries, and impaired mammary gland
      development. In agreement with this phenotype, the expression pattern of the
      ERalpha((EAAE/EAAE)) mutant mice in liver obtained by genome-wide gene expression
      profiling supports the observation of a near-complete loss of estrogen-dependent
      gene regulation in comparison with the wild type. Further gene expression
      analyses to validate the results of the microarray data were performed by
      quantitative RT-PCR. The analyses indicate that both gene activation and
      repression by estrogen-bound ERalpha rely on an intact DBD in vivo.

PMID- 19574449
TI  - Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta-cells.
AB  - High-density lipoproteins (HDLs) protect pancreatic beta-cells against apoptosis.
      This property might relate to the increased risk to develop diabetes in patients
      with low HDL blood levels. However, the mechanisms by which HDLs protect beta
      cells are poorly characterized. Here we used a transcriptomic approach to
      identify genes differentially modulated by HDLs in beta-cells subjected to
      apoptotic stimuli. The transcript encoding 4E-binding protein (4E-BP)1 was up
      regulated by serum starvation, and HDLs blocked this increase. 4E-BP1 inhibits
      cap-dependent translation in its non- or hypophosphorylated state but it loses
      this ability when hyperphosphorylated. At the protein level, 4E-BP1 was also up
      regulated in response to starvation and IL-1beta, and this was blunted by HDLs.
      Whereas an ectopic increase of 4E-BP1 expression induced beta-cell death,
      silencing 4E-BP1 increase with short hairpin RNAs inhibited the apoptotic
      inducing capacities of starvation. HDLs can therefore protect beta-cells by
      blocking 4E-BP1 protein expression, but this is not the sole protective mechanism
      activated by HDLs. Indeed, HDLs blocked apoptosis induced by endoplasmic
      reticulum stress with no associated decrease in total 4E-BP1 induction. Although,
      HDLs favored the phosphorylation, and hence the inactivation of 4E-BP1 in these
      conditions, this appeared not to be required for HDL protection. Our results
      indicate that HDLs can protect beta-cells through modulation of 4E-BP1 depending
      on the type of stress stimuli.

PMID- 19574450
TI  - Inhibition of prostate cancer cell growth by second-site androgen receptor
      antagonists.
AB  - The impact of ligand binding on nuclear receptor (NR) structure and the ability
      of target cells to distinguish between different receptor-ligand complexes are
      key determinants of the pharmacological activity of NR ligands. However, until
      relatively recently, these mechanistic insights have not been used in a
      prospective manner to develop screens for NR modulators with specific therapeutic
      activities. Driven by the need for unique androgen receptor (AR) antagonists that
      retain activity in hormone-refractory prostate cancer, we developed and applied a
      conformation-based screen to identify AR antagonists that were mechanistically
      distinct from existing drugs of this class. Two molecules were identified by
      using this approach, D36 and D80, which interact with AR in a unique manner and
      allosterically inhibit AR agonist activity. Unlike the clinically important
      antiandrogens, casodex and hydroxyflutamide, both D36 and D80 block androgen
      action in cellular models of hormone-refractory prostate cancer. Mechanistically,
      these compounds further distinguish themselves from classical AR antagonists in
      that they do not promote AR nuclear translocation and quantitatively inhibit the
      association of AR with DNA even under conditions of overexpression. Although the
      therapeutic potential of these antiandrogens is apparent, it is the demonstration
      that it is possible, to modulate the interaction of cofactors with agonist
      activated AR, using second-site modulators, that has the greatest potential with
      respect to the therapeutic exploitation of AR and other NRs.

PMID- 19574452
TI  - Surviving mass extinction by bridging the benthic/planktic divide.
AB  - Evolution of planktic organisms from benthic ancestors is commonly thought to
      represent unidirectional expansion into new ecological domains, possibly only
      once per clade. For foraminifera, this evolutionary expansion occurred in the
      Early-Middle Jurassic, and all living and extinct planktic foraminifera have been
      placed within 1 clade, the Suborder Globigerinina. The subsequent radiation of
      planktic foraminifera in the Jurassic and Cretaceous resulted in highly diverse
      assemblages, which suffered mass extinction at the end of the Cretaceous, leaving
      an impoverished assemblage dominated by microperforate triserial and biserial
      forms. The few survivor species radiated to form diverse assemblages once again
      in the Cenozoic. There have, however, long been doubts regarding the monophyletic
      origin of planktic foraminifera. We present surprising but conclusive genetic
      evidence that the Recent biserial planktic Streptochilus globigerus belongs to
      the same biological species as the benthic Bolivina variabilis, and geochemical
      evidence that this ecologically flexible species actively grows within the open
      ocean surface waters, thus occupying both planktic and benthic domains. Such a
      lifestyle (tychopelagic) had not been recognized as adapted by foraminifera.
      Tychopelagic are endowed with great ecological advantage, enabling rapid
      recolonization of the extinction-susceptible pelagic domain from the benthos. We
      argue that the existence of such forms must be considered in resolving
      foraminiferal phylogeny.

PMID- 19574453
TI  - Protein dynamics-induced variation of excitation energy transfer pathways.
AB  - Strong anticorrelation between the fluorescence emission of different emitters is
      observed by employing single-molecule fluorescence spectroscopy on photosystem I
      at cryogenic temperatures. This anticorrelation demonstrates a time-dependent
      interaction between pigments participating in the exciton transfer chain,
      implying that uniquely defined energy transfer pathways within the complex do not
      exist. Fluctuations of the chromophores themselves or their immediate protein
      surroundings induce changes in their site energy, and, as a consequence, these
      fluctuations change the coupling within the excitation transfer pathways. The
      time scales of the site energy fluctuations of the individual emitters do not
      meet the time scales of the observed correlated emission behavior. Therefore, the
      emitters must be fed individually by energetically higher lying states, causing
      the observed intensity variations. This phenomenon is shown for photosystem I
      pigment-protein complexes from 2 different cyanobacteria (Thermosynechococcus
      elongatus and Synechocystis sp. PCC 6803) with strongly different spectral
      properties underlining the general character of the findings. The variability of
      energy transfer pathways might play a key role in the extreme robustness of light
      harvesting systems in general.

PMID- 19574451
TI  - Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor
      autoantibodies in lupus.
AB  - Using the Unc93b1 3d mutation that selectively abolishes nucleic acid-binding
      Toll-like receptor (TLR) (TLR3, -7, -9) signaling, we show these endosomal TLRs
      are required for optimal production of IgG autoAbs, IgM rheumatoid factor, and
      other clinical parameters of disease in 2 lupus strains, B6-Fas(lpr) and BXSB.
      Strikingly, treatment with lipid A, an autoAb-inducing TLR4 agonist, could not
      overcome this requirement. The 3d mutation slightly reduced complete Freund's
      adjuvant (CFA)-mediated antigen presentation, but did not affect T-independent
      type 1 or alum-mediated T-dependent humoral responses or TLR-independent IFN
      production induced by cytoplasmic nucleic acids. These findings suggest that
      nucleic acid-sensing TLRs might act as an Achilles' heel in susceptible
      individuals by providing a critical pathway by which relative tolerance for
      nucleic acid-containing antigens is breached and systemic autoimmunity ensues.
      Importantly, this helps provide an explanation for the high frequency of anti
      nucleic acid Abs in lupus-like systemic autoimmunity.

PMID- 19574454
TI  - Reception of Slit requires only the chondroitin-sulphate-modified extracellular
      domain of Syndecan at the target cell surface.
AB  - Syndecan (Sdc) is a conserved transmembrane heparan sulfate proteoglycan (HSPG)
      bearing additional chondroitin sulfate (CS) modifications on its extracellular
      domain. In vertebrates, this extracellular domain of Sdc is shed and acts as a
      soluble effector of cellular communication events, and its cytoplasmic domain
      participates in intracellular signaling needed to maintain epithelial integrity.
      In Drosophila, Sdc has been shown to be necessary for Slit signaling-dependent
      axon and myotube guidance during CNS development and muscle pattern formation. We
      report that Sdc acts in a cell-autonomous manner in Slit-receiving cells and that
      its membrane-anchored extracellular domain is sufficient to mediate Slit
      signaling. Sdc activity can be replaced by the human homolog hsdc2. However, the
      HSPG Dally-like protein (Dlp), which lacks CS modifications at its extracellular
      domain, can only partially substitute for Sdc function, and its activity is not
      restricted to the Slit target cells. Our results suggest that Sdc and Dlp act in
      a cooperative but nonredundant fashion in axon and myotube guidance. We propose
      that Dlp, which lacks CS modifications, participates in the transfer of Slit from
      its site of expression to the target cells, where CS-modified Sdc concentrates
      and presents the ligand.

PMID- 19574455
TI  - 5'-triphosphate RNA requires base-paired structures to activate antiviral
      signaling via RIG-I.
AB  - The ATPase retinoid acid-inducible gene (RIG)-I senses viral RNA in the cytoplasm
      of infected cells and subsequently activates cellular antiviral defense
      mechanisms. RIG-I recognizes molecular structures that discriminate viral from
      host RNA. Here, we show that RIG-I ligands require base-paired structures in
      conjunction with a free 5'-triphosphate to trigger antiviral signaling. Hitherto
      unavailable chemically synthesized 5'-triphosphate RNA ligands do not trigger RIG
      I-dependent IFN production in cells, and they are unable to trigger the ATPase
      activity of RIG-I without a base-paired stretch. Consistently, immunostimulatory
      RNA from cells infected with a virus recognized by RIG-I is sensitive to double
      strand, but not single-strand, specific RNases. In vitro, base-paired stretches
      and the 5'-triphosphate bind to distinct sites of RIG-I and synergize to trigger
      the induction of signaling competent RIG-I multimers. Strengthening our model of
      a bipartite molecular pattern for RIG-I activation, we show that the activity of
      supposedly "single-stranded" 5'-triphosphate RNAs generated by in vitro
      transcription depends on extended and base-paired by-products inadvertently, but
      commonly, produced by this method. Together, our findings accurately define a
      minimal molecular pattern sufficient to activate RIG-I that can be found in viral
      genomes or transcripts.

PMID- 19574456
TI  - Development of GFP-based biosensors possessing the binding properties of
      antibodies.
AB  - Proteins that can bind specifically to targets that also have an intrinsic
      property allowing for easy detection could facilitate a multitude of
      applications. While the widely used green fluorescent protein (GFP) allows for
      easy detection, attempts to insert multiple binding loops into GFP to impart
      affinity for a specific target have been met with limited success because of the
      structural sensitivity of the GFP chromophore. In this study, directed evolution
      using a surrogate loop approach and yeast surface display yielded a family of GFP
      scaffolds capable of accommodating 2 proximal, randomized binding loops. The
      library of potential GFP-based binders or ''GFAbs'' was subsequently mined for
      GFAbs capable of binding to protein targets. Identified GFAbs bound with
      nanomolar affinity and required binding contributions from both loops indicating
      the advantage of a dual loop GFAb platform. Finally, GFAbs were solubly produced
      and used as fluorescence detection reagents to demonstrate their utility.

PMID- 19574457
TI  - Virtual taphonomy using synchrotron tomographic microscopy reveals cryptic
      features and internal structure of modern and fossil plants.
AB  - While more commonly applied in zoology, synchrotron radiation X-ray tomographic
      microscopy (SRXTM) is well-suited to nondestructive study of the morphology and
      anatomy of both fossil and modern plants. SRXTM uses hard X-rays and a
      monochromatic light source to provide high-resolution data with little beam
      hardening, resulting in slice data with clear boundaries between materials.
      Anatomy is readily visualized, including various planes of section from a single
      specimen, as clear as in traditional histological sectioning at low
      magnifications. Thus, digital sectioning of rare or difficult material is
      possible. Differential X-ray attenuation allows visualization of different layers
      or chemistries to enable virtual 3-dimensional (3D) dissections of material.
      Virtual potential fossils can be visualized and digital tissue removal reveals
      cryptic underlying morphology. This is essential for fossil identification and
      for comparisons between assemblages where fossils are preserved by different
      means. SRXTM is a powerful approach for botanical studies using morphology and
      anatomy. The ability to gain search images in both 2D and 3D for potential
      fossils gives paleobotanists a tool--virtual taphonomy--to improve our
      understanding of plant evolution and paleobiogeography.

PMID- 19574458
TI  - Processing and phosphorylation of the Fat receptor.
AB  - The Drosophila tumor suppressors fat and discs overgrown (dco) function within an
      intercellular signaling pathway that controls growth and polarity. fat encodes a
      transmembrane receptor, but post-translational regulation of Fat has not been
      described. We show here that Fat is subject to a constitutive proteolytic
      processing, such that most or all cell surface Fat comprises a heterodimer of
      stably associated N- and C-terminal fragments. The cytoplasmic domain of Fat is
      phosphorylated, and this phosphorylation is promoted by the Fat ligand Dachsous.
      dco encodes a kinase that influences Fat signaling, and Dco is able to promote
      the phosphorylation of the Fat intracellular domain in cultured cells and in
      vivo. Evaluation of dco mutants indicates that they affect Fat's influence on
      growth and gene expression but not its influence on planar cell polarity. Our
      observations identify processing and phosphorylation as post-translational
      modifications of Fat, correlate the phosphorylation of Fat with its activation by
      Dachsous in the Fat-Warts pathway, and enhance our understanding of the
      requirement for Dco in Fat signaling.

PMID- 19574459
TI  - Type I interferon (IFN)-dependent activation of Mnk1 and its role in the
      generation of growth inhibitory responses.
AB  - We provide evidence for the existence of an IFN-regulated cellular pathway
      involving the mitogen-activated protein kinase (MAPK)-integrating kinase (Mnk) 1.
      Our data demonstrate that type I (alpha, beta) IFNs induce
      phosphorylation/activation of Mnk1, which, in turn, regulates phosphorylation of
      the eukaryotic initiation factor 4E (eIF4E) on Ser-209. Such Mnk activation
      depends on upstream engagement of Jak1, and requires downstream activation of the
      Mek/Erk MAPK pathway. In studies using double Mnk1-/-Mnk2-/- knockout mouse
      embryonic fibroblasts (MEFs), we found that engagement of Mnk kinases is
      essential for mRNA translation of the Isg15 and Isg54 genes, suggesting an
      important role for this pathway in mRNA translation of IFN-stimulated genes
      (ISGs). Importantly, our data demonstrate that pharmacological inhibition of Mnk
      kinases or siRNA-mediated knockdown of Mnk1 and Mnk2 results in partial reversal
      of the suppressive effects of IFNalpha on normal and leukemic hematopoietic
      progenitors, establishing a key role for this pathway in the generation of the
      growth inhibitory effects of type I IFNs. Together, our findings establish that
      the Mnk/eIF4E kinase pathway is activated in an IFN-inducible manner and plays
      important roles in mRNA translation for ISGs and generation of IFN-inducible anti
      proliferative responses.

PMID- 19574460
TI  - Control of cell membrane tension by myosin-I.
AB  - All cell functions that involve membrane deformation or a change in cell shape
      (e.g., endocytosis, exocytosis, cell motility, and cytokinesis) are regulated by
      membrane tension. While molecular contacts between the plasma membrane and the
      underlying actin cytoskeleton are known to make significant contributions to
      membrane tension, little is known about the molecules that mediate these
      interactions. We used an optical trap to directly probe the molecular
      determinants of membrane tension in isolated organelles and in living cells.
      Here, we show that class I myosins, a family of membrane-binding, actin-based
      motor proteins, mediate membrane/cytoskeleton adhesion and thus, make major
      contributions to membrane tension. These studies show that class I myosins
      directly control the mechanical properties of the cell membrane; they also
      position these motor proteins as master regulators of cellular events involving
      membrane deformation.

PMID- 19574462
TI  - Efficient computation of optimal actions.
AB  - Optimal choice of actions is a fundamental problem relevant to fields as diverse
      as neuroscience, psychology, economics, computer science, and control
      engineering. Despite this broad relevance the abstract setting is similar: we
      have an agent choosing actions over time, an uncertain dynamical system whose
      state is affected by those actions, and a performance criterion that the agent
      seeks to optimize. Solving problems of this kind remains hard, in part, because
      of overly generic formulations. Here, we propose a more structured formulation
      that greatly simplifies the construction of optimal control laws in both discrete
      and continuous domains. An exhaustive search over actions is avoided and the
      problem becomes linear. This yields algorithms that outperform Dynamic
      Programming and Reinforcement Learning, and thereby solve traditional problems
      more efficiently. Our framework also enables computations that were not possible
      before: composing optimal control laws by mixing primitives, applying
      deterministic methods to stochastic systems, quantifying the benefits of error
      tolerance, and inferring goals from behavioral data via convex optimization.
      Development of a general class of easily solvable problems tends to accelerate
      progress--as linear systems theory has done, for example. Our framework may have
      similar impact in fields where optimal choice of actions is relevant.

PMID- 19574461
TI  - miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy.
AB  - Cardiac hypertrophy is accompanied by maladaptive cardiac remodeling, which leads
      to heart failure or sudden death. MicroRNAs (miRNAs) are a class of small,
      noncoding RNAs that mediate posttranscriptional gene silencing. Recent studies
      show that miRNAs are involved in the pathogenesis of hypertrophy, but their
      signaling regulations remain to be understood. Here, we report that miR-23a is a
      pro-hypertrophic miRNA, and its expression is regulated by the transcription
      factor, nuclear factor of activated T cells (NFATc3). The results showed that miR
      23a expression was up-regulated upon treatment with the hypertrophic stimuli
      including isoproterenol and aldosterone. Knockdown of miR-23a could attenuate
      hypertrophy, suggesting that miR-23a is able to convey the hypertrophic signal.
      In exploring the molecular mechanism by which miR-23a is up-regulated, we
      identified that NFATc3 could directly activate miR-23a expression through the
      transcriptional machinery. The muscle specific ring finger protein 1, an anti
      hypertrophic protein, was identified to be a target of miR-23a. Its translation
      could be suppressed by miR-23a. Our data provide a model in which the miRNA
      expression is regulated by the hypertrophic transcriptional factor.

PMID- 19574463
TI  - Don E. Detmer and the American Medical Informatics Association: an appreciation.
AB  - Don E. Detmer has served as President and Chief Executive Officer of the American
      Medical Informatics Association (AMIA) for the past five years, helping to set a
      course for the organization and demonstrating remarkable leadership as AMIA has
      evolved into a vibrant and influential professional association. On the occasion
      of Dr. Detmer's retirement, we fondly reflect on his professional life and his
      many contributions to biomedical informatics and, more generally, to health care
      in the U.S. and globally.

PMID- 19574465
TI  - National academy of clinical biochemistry laboratory medicine practice
      guidelines: follow-up testing for metabolic disease identified by expanded
      newborn screening using tandem mass spectrometry; executive summary.
AB  - BACKGROUND: Almost all newborns in the US are screened at birth for multiple
      inborn errors of metabolism using tandem mass spectrometry. Screening tests are
      designed to be sufficiently sensitive so that cases are not missed. The NACB
      recognized a need for standard guidelines for laboratory confirmation of a
      positive newborn screen such that all babies would benefit from equal and optimal
      follow-up by confirmatory testing. METHODS: A committee was formed to review
      available data pertaining to confirmatory testing. The committee evaluated
      previously published guidelines, published methodological and clinical studies,
      clinical case reports, and expert opinion to support optimal confirmatory
      testing. Grading was based on guidelines adopted from criteria derived from the
      US Preventive Services Task Force and on the strength of recommendations and the
      quality of the evidence. Three primary methods of analyte measurement were
      evaluated for confirmatory testing including measurement of amino acids, organic
      acids, and carnitine esters. The committee graded the evidence for diagnostic
      utility of each test for the screened conditions. RESULTS: Ample data and
      experience were available to make strong recommendations for the practice of
      analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong
      recommendations were made for the follow-up test menu for many disorders,
      particularly those with highest prevalence. Fewer data exist to determine the
      impact of newborn screening on patient outcomes in all but a few disorders. The
      guidelines also provide an assessment of developing technology that will fuel a
      refinement of current practice and ultimate expansion of the diseases detectable
      by tandem mass spectrometry. CONCLUSIONS: Guidelines are provided for optimal
      follow-up testing for positive newborn screens using tandem mass spectrometry.
      The committee regards these tests as reliable and currently optimal for follow-up
      testing. .

PMID- 19574466
TI  - Circulating concentrations of follistatin-like 1 in healthy individuals and
      patients with acute coronary syndrome as assessed by an immunoluminometric
      sandwich assay.
AB  - BACKGROUND: Follistatin-like 1 (FSTL1) is a 308-amino acid secreted glycoprotein.
      Tissue levels of FSTL1 are induced in animal models and patients with chronic
      inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be
      measured in the human circulation and used as a biomarker in acute coronary
      syndrome (ACS). METHODS: We developed an immunoluminometric assay (ILMA),
      assessed the preanalytic characteristics of FSTL1, and determined circulating
      FSTL1 concentrations in 120 apparently healthy individuals and 216 patients with
      ACS. RESULTS: The assay had a limit of detection of 0.17 microg/L, limit of
      quantification of 1.02 microg/L, intraassay imprecision of < or =12.7%, and
      interassay imprecision of < or =15.4%. Selectivity was demonstrated with size
      exclusion chromatography and lack of cross-reactivity with related proteins. The
      assay was not appreciably influenced by unrelated biological substances. FSTL1 in
      serum or whole blood was stable at room temperature for 48 h and was resistant to
      4 freeze-thaw cycles. Measured FSTL1 concentrations in citrated plasma and
      heparin-treated plasma were 18% and 17% lower, respectively, than concentrations
      measured in serum. Apparently healthy individuals presented with a median FSTL1
      serum concentration of 7.18 (range 1.06-18.49) microg/L. Serum FSTL1
      concentrations were increased in ACS and related to the risk of all-cause
      mortality during follow-up. CONCLUSIONS: The ILMA permits detection of FSTL1 in
      human serum and plasma. We expect that the favorable preanalytic characteristics
      of FSTL1 and the reference limits defined here for apparently healthy individuals
      will facilitate future studies of FSTL1 as a biomarker in various disease
      settings, including ACS.

PMID- 19574467
TI  - A commutable cytomegalovirus calibrator is required to improve the agreement of
      viral load values between laboratories.
AB  - BACKGROUND: Viral load testing for cytomegalovirus (CMV) is an important
      diagnostic tool for the management of transplant recipients and immunocompromised
      individuals; however, inconsistency among laboratories in quantitative
      measurements of viral load limits interinstitutional comparisons. These
      inconsistencies stem from the lack of assays cleared by the US Food and Drug
      Administration, the absence of international standards, the wide variety of CMV
      extraction and -detection methods, and differences in materials used for
      calibration. A critical component of standardization is the use of calibrators
      that are traceable and commutable. METHODS: Bland-Altman plots and prediction
      ellipses were used to test the commutability of 2 CMV calibrators for 2 different
      quantification methods. RESULTS: Tests with 2 methods showed 1 calibrator to be
      commutable and the other to be noncommutable. The results for the commutable
      calibrator were within the 95% prediction interval of the clinical samples in the
      Bland-Altman plot and within the 95% prediction ellipse for a simulated
      commutable calibrator, whereas the results for the noncommutable calibrator were
      not within these prediction intervals. When used to calibrate patient results,
      only the commutable calibrator, the OptiQuant CMV(tc) Calibration Panel,
      significantly improved the comparability of viral loads for the 2 different
      measurement methods. CONCLUSIONS: This study demonstrates that an important goal
      in the effort to improve healthcare for patients with CMV-related disease is the
      establishment of traceable and commutable reference materials, including both
      calibrators and controls. .

PMID- 19574469
TI  - Method for the selective measurement of amino-terminal variants of procalcitonin.
AB  - BACKGROUND: Procalcitonin (PCT) is an established marker for diagnosing and
      monitoring bacterial infections. Full-length PCT [116 amino acids that make up
      procalcitonin (PCT1-116)] can be truncated, leading to des-Ala-Pro-PCT (des
      Alanin-Prolin-Procalcitonin; PCT3-116). Current immunoassays for PCT ("total
      PCT") use antibodies directed against internal epitopes and are unable to
      distinguish amino-terminal PCT variants. Here we describe the development of
      monoclonal antibodies recognizing the amino-termini of PCT1-116 and PCT3-116 and
      their use in the selective measurement of these PCT species. METHODS: With newly
      developed monoclonal antibodies against the amino-termini of PCT1-116 and PCT3
      116, and an antibody against the katacalcin moiety of PCT, we developed and
      characterized immunoluminometric assays for the 2 PCT peptides. We comparatively
      assessed the kinetics of PCT variants in a human endotoxemia model. RESULTS:
      Monoclonal antibodies against the amino-termini of PCT1-116 and PCT3-116 showed
      <1% cross-reactivity with other PCT-related peptides. The sandwich assays for
      PCT1-116 and PCT3-116 had functional assay sensitivities of 5 and 1.2 pmol/L,
      respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1
      116 was stable for 6 h at 22 degrees C and 24 h at 4 degrees C, and PCT3-116 was
      stable for at least 24 h at both temperatures. During experimental endotoxemia in
      healthy people, both PCT1-116 and PCT3-116 increased early in parallel with total
      PCT, but further increases in PCT1-116 were significantly slower than for PCT3
      116 (P = 0.0049) and total PCT (P = 0.0024). CONCLUSIONS: The new assays
      selectively measure PCT1-116 and PCT3-116. Both PCT species increase early during
      endotoxemia but differ in their kinetics thereafter. The selective measurement of
      PCT species with different in vivo kinetics may be useful in improving PCT-guided
      therapies.

PMID- 19574468
TI  - Monitoring therapeutic efficacy by real-time detection of Mycobacterium
      tuberculosis mRNA in sputum.
AB  - BACKGROUND: Current laboratory methods for monitoring the response to therapy for
      tuberculosis (TB) rely on mycobacterial culture. Their clinical usefulness is
      therefore limited by the slow growth rate of Mycobacterium tuberculosis. Rapid
      methods to reliably quantify the response to anti-TB drugs are desirable.
      METHODS: We developed 2 real-time PCR assays that use hydrolysis probes to target
      DNA of the IS6110 insertion element and mRNA for antigen 85B. The nucleic acids
      are extracted directly from concentrated sputum samples decontaminated with
      sodium hydroxide and N-acetyl-L-cysteine. We prospectively compared these assays
      with results obtained by sputum mycobacterial culture for patients receiving anti
      TB therapy. RESULTS: Sixty-five patients with newly diagnosed TB and receiving a
      standardized first-line anti-TB drug regimen were evaluated at week 2 and at
      months 1, 2, and 4 after therapy initiation. Both the DNA PCR assay (98.5%
      positive) and the mRNA reverse-transcription PCR (RT-PCR) assay (95.4% positive)
      were better than standard Ziehl-Neelsen staining techniques (83.1%) for detecting
      M. tuberculosis in culture-positive sputum samples. The overall agreement between
      culture and mRNA RT-PCR results for all 286 sputum samples was 87.1%, and
      compared with culture, the mRNA RT-PCR assay's diagnostic sensitivity and
      specificity were 85.2% and 88.6%, respectively. For monitoring efficacy of
      therapy, mRNA RT-PCR results paralleled those of culture at the follow-up time
      points. CONCLUSIONS: The continued presence of viable M. tuberculosis according
      to culture and results obtained by RT-PCR analysis of antigen 85B mRNA correlated
      clinically with resistance to anti-TB drugs, whereas the DNA PCR assay showed a
      high false-positive rate. This mRNA RT-PCR assay may allow rapid monitoring of
      the response to anti-TB therapy.

PMID- 19574470
TI  - Pharmacogenomics of tamoxifen therapy.
AB  - BACKGROUND: Tamoxifen is a standard endocrine therapy for the prevention and
      treatment of steroid hormone receptor-positive breast cancer. CONTENT: Tamoxifen
      requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation
      of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the
      parent drug, both metabolites have an approximately 100-fold greater affinity for
      the estrogen receptor and the ability to inhibit cell proliferation. The
      polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent
      mechanistic, pharmacologic, and clinical evidence suggests that genetic variants
      and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of
      active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In
      particular, nonfunctional (poor metabolizer) and severely impaired (intermediate
      metabolizer) CYP2D6 alleles are associated with higher recurrence rates. SUMMARY:
      Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6)
      genotyping before treatment to predict metabolizer status may open new avenues
      for individualizing endocrine treatment, with the maximum benefit being expected
      for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the
      selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used
      to treat hot flashes, should be avoided because they severely impair formation of
      the active metabolites.

PMID- 19574471
TI  - Nocturnal hypoglycaemia in type 1 diabetes--frequency and predictive factors.
AB  - BACKGROUND: Nocturnal hypoglycaemia (NH) remains a problem in type 1 diabetes and
      spontaneous asymptomatic NH may be a risk factor for sudden death ('Dead in Bed'
      syndrome). AIMS: To explore whether any predictive relationship exists between
      the average or time-specific glycaemia and the occurrence of NH. METHODS: Twenty
      five healthy patients with type 1 diabetes underwent two separate overnight
      periods of continuous glucose monitoring (CGM) using a MMT-7002 Medtronic MiniMed
      System. There was a 6-week interval before the second monitoring period. CGM
      glucose levels recorded between 23:00 and 08:00 h defined the nocturnal period
      and recorded glucose monitoring levels <3.5 mmol/l for at least 10 min during
      this time-defined NH. A CGM recording at 23:00 h and 08:00 h were taken as the
      bedtime and fasting glucose levels, respectively. RESULTS: The mean +/- SD age
      was 37 +/- 7 years and duration of diabetes 13 +/- 7 years; 16 (64%) were on long
      acting analogue insulin. Forty-nine CGM data sets were recorded. Fourteen
      episodes of NH occurred in 12 patients (Group 1), 13 patients (Group 2) had no
      NH. Group 1 (NH) had a lower mean bedtime glucose recorded compared with Group 2
      (7.7 +/- 4.3 vs. 11.4 +/- 4.0 mmol/l, P = 0.0035). Fasting glucose level was also
      lower in Group 1 following the occurrence of NH (P = 0.014). There was no
      difference in the type of insulin used between the two groups. CONCLUSION: Our
      data show that in normal day to day settings, NH is common and that the bedtime
      glucose level is a significant predictive factor.

PMID- 19574472
TI  - Cytokine and autoantibody profiling related to histopathological features in
      primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate a potential correlation between circulating cytokine
      and autoantibody levels and histopathological features in subgroups of patients
      with primary SS (pSS). METHODS: Minor salivary gland biopsies from a cohort of
      141 patients fulfilling the American-European consensus classification criteria
      for pSS were re-examined and grouped according to focus score (FS) and germinal
      centre (GC) status; serum samples were analysed for autoantibodies, chemokines
      and cytokines. RESULTS: Of the 115 available biopsies, 18 (16%) lacked
      characteristic focal mononuclear cell infiltrates [FS < 1 (FS-)] but patients
      were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, eotaxin, IFN-alpha and IL-4 levels
      were significantly increased in the 27 (23%) patients with ectopic GC formation
      (GC+) in the salivary glands compared with the GC- patients (n = 70). In
      addition, minor differences in cytokine levels were found when comparing age
      groups. CONCLUSION: Degenerative changes observed in the minor salivary glands of
      patients with pSS may represent 'burned out' inflammation. The elevated levels of
      IL-4 found in these patients may influence the reduced salivary flow observed in
      GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1beta and
      the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+
      patients. Differences in cytokine levels may be utilized when sub-grouping the SS
      patients into disease phases and may consequently have implications for
      treatment.

PMID- 19574473
TI  - Mechanism of REP27 protein action in the D1 protein turnover and photosystem II
      repair from photodamage.
AB  - The function of the REP27 protein (GenBank accession no. EF127650) in the
      photosystem II (PSII) repair process was elucidated. REP27 is a nucleus-encoded
      and chloroplast-targeted protein containing two tetratricopeptide repeat (TPR)
      motifs, two putative transmembrane domains, and an extended carboxyl (C)-terminal
      region. Cell fractionation and western-blot analysis localized the REP27 protein
      in the Chlamydomonas reinhardtii chloroplast thylakoids. A folding model for
      REP27 suggested chloroplast stroma localization for amino- and C-terminal regions
      as well as the two TPRs. A REP27 gene knockout strain of Chlamydomonas, termed
      the rep27 mutant, was employed for complementation studies. The rep27 mutant was
      aberrant in the PSII-repair process and had substantially lower than wild-type
      levels of D1 protein. Truncated REP27 cDNA constructs were made for
      complementation of rep27, whereby TPR1, TPR2, TPR1+TPR2, or the C-terminal
      domains were deleted. rep27-complemented strains minus the TPR motifs showed
      elevated levels of D1 in thylakoids, comparable to those in the wild type, but
      the PSII photochemical efficiency of these strains was not restored, suggesting
      that the functionality of the PSII reaction center could not be recovered in the
      absence of the TPR motifs. It is suggested that TPR motifs play a role in the
      functional activation of the newly integrated D1 protein in the PSII reaction
      center. rep27-complemented strains missing the C-terminal domain showed low
      levels of D1 protein in thylakoids as well as low PSII photochemical efficiency,
      comparable to those in the rep27 mutant. Therefore, the C-terminal domain is
      needed for a de novo biosynthesis and/or assembly of D1 in the photodamaged PSII
      template. We conclude that REP27 plays a dual role in the regulation of D1
      protein turnover by facilitating cotranslational biosynthesis insertion (C
      terminal domain) and activation (TPR motifs) of the nascent D1 during the PSII
      repair process.

PMID- 19574474
TI  - Magnetic resonance imaging findings of the lumbar spine in elite horseback
      riders: correlations with back pain, body mass index, trunk/leg-length
      coefficient, and riding discipline.
AB  - BACKGROUND: Most orthopaedic problems experienced by competitive horseback riders
      are related to pain in the lower back, hip joint, and hamstring muscles. Riders
      especially, show jumpers-are frequently hampered in their performance because of
      lumbar pain. To date, there has been no research into lumbar disk degeneration in
      elite competitive riders. HYPOTHESIS: Competitive horseback riding accelerates
      lumbar disk degeneration. STUDY DESIGN: Cross-sectional study; Level of evidence,
      3. METHODS: Fifty-eight elite riders (18 men, 40 women; mean age, 32.4 years) and
      a control group of 30 nonriding volunteers (17 men, 13 women; mean age, 28.7
      years) were evaluated for lumbar disk degeneration, cross-sectional area of
      paraspinal muscles, spondylolysis, and spondylolisthesis, using magnetic
      resonance imaging (MRI). The prevalence of disk degeneration between the 2 groups
      was compared, and the relationship was investigated between low back pain (LBP),
      riding discipline, body mass index (BMI), trunk/leg-length coefficient, and MRI
      results. RESULTS: Eighty-eight percent of elite riders (n = 51) had a history of
      LBP, versus 33% of the controls (P < .05). There was no statistical difference
      for the prevalence of LBP among the different riding disciplines. However, there
      was a high rate of pathologic T2 signal intensity of the lumbar intervertebral
      disk among riders-specifically, dressage riders-yet no significant increase when
      compared with controls. History of LBP symptoms, riding discipline, BMI, and
      trunk/leg-length ratio had no significant effect on the development of lumbar
      disk degeneration. Occult fractures of the pars interarticularis and manifest
      spondylolysis were not seen for any rider. Two controls had spondylolisthesis
      Meyerding grade 1 not associated with back pain. CONCLUSION: Although riders have
      a high prevalence of LBP, there is no conclusive MRI evidence to suggest that the
      cause lies in undue disk degeneration, spondylolysis, spondylolisthesis, or
      pathologic changes of the paraspinal muscles of the lumbar spine.

PMID- 19574475
TI  - Identification of athletes at future risk of anterior cruciate ligament ruptures
      by neuromuscular screening.
AB  - BACKGROUND: A high percentage of female athletes who sustain an anterior cruciate
      ligament (ACL) rupture suffer serious long-term consequences such as
      osteoarthritis and disability. Thus, identification of risk factors has high
      clinical relevance in the prevention of ACL rupture. Hypothesis Noninjured
      athletes with low knee flexor electromyography (EMG) preactivity and high knee
      extensor EMG preactivity during sidecutting are at increased risk of future ACL
      rupture. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS:
      Fifty-five elite female athletes (team handball and soccer) aged 24 +/- 5 years
      with no history of ACL injury were tested for EMG preactivity of vastus lateralis
      and medialis, rectus femoris, semitendinosus, and biceps femoris during a
      standardized side-cutting maneuver. The incidence of ACL ruptures was registered
      in the following 2 match seasons. RESULTS: During the subsequent 2 match seasons,
      5 athletes sustained a confirmed noncontact ACL rupture. Before injury, all 5
      players displayed a neuromuscular pattern that differed from the noninjured
      players, characterized by reduced EMG preactivity for the semitendinosus (ST) and
      elevated EMG preactivity for the vastus lateralis (VL) (P < .01). On the basis of
      these findings, a high-risk zone was defined as one standard deviation above the
      mean VL-ST difference. In our population, 5 of 10 subjects with a VL-ST
      difference in this zone sustained an ACL injury during the study period.
      CONCLUSION: In the present study, currently noninjured female athletes with
      reduced EMG preactivity of the ST and increased EMG preactivity of the VL during
      side cutting were at increased risk of future noncontact ACL rupture. Our data
      indicate that a high-risk zone can be used to identify noninjured players at high
      risk of future ACL rupture. Consequently, individual preventive efforts can be
      introduced in time. However, large prospective studies are needed to confirm this
      finding before definitive clinical recommendations can be made.

PMID- 19574476
TI  - How sweet it is: identification of vacuolar sucrose transporters.

PMID- 19574477
TI  - Iron overload in Asia.
AB  - In a remarkable study in this issue of Blood, Lok and colleagues describe the
      genotypic and phenotypic characteristics of hereditary hemochromatosis in 42
      cases in 8 distinct families of Asian origin.

PMID- 19574478
TI  - "Self"-reflection by KIR.
AB  - Significant debate exists over the proposed mechanisms by which NK receptor
      expression coordinates with the acquisition of function and titration of
      responsiveness, a process called NK-cell education. In this issue of Blood,
      Andersson and colleagues provide new insights into the mechanisms underlying NK
      cell repertoire formation and the modulation of NK-cell function.

PMID- 19574479
TI  - Mighty mouse.
AB  - In this issue of Blood, ter Brugge and colleagues describe the results of their
      efforts to express SV40 T antigen in mature B cells of mice. As a consequence of
      T antigen expression, B cells develop normally but, upon aging, mice show an
      accumulation of monoclonal CD5(+) B cells and have a chronic lymphocytic leukemia
      like phenotype.

PMID- 19574480
TI  - Megakaryocytes survive without survivin.
AB  - Survivin has been described as an important regulator of late mitosis and as
      antiapoptotic in various cells. In this issue of Blood, Wen and colleagues
      describe a megakaryocyte-specific knockout of survivin, with no influence on
      megakaryocyte survival, and a stimulating effect on polyploidy.

PMID- 19574481
TI  - Plasma quantitation of JAK2 mutation is not suitable as a clinical test: an
      artifact of storage.

PMID- 19574484
TI  - Incidence of second cancers after allogeneic hematopoietic stem cell
      transplantation using reduced-dose radiation.

PMID- 19574485
TI  - Low versus high I-131 dose for remnant ablation in differentiated thyroid cancer.

PMID- 19574486
TI  - Breast cancer subtypes based on ER/PR and Her2 expression: comparison of
      clinicopathologic features and survival.
AB  - OBJECTIVE: To compare the clinicopathologic features and survival in the four
      breast cancer subtypes defined by immunohistochemistry (IHC) expression of
      estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2-; ER/PR-, Her2+; and ER/PR
      , Her2-. METHODS: A 7-year retrospective study of 1134 invasive breast cancer
      subjects. Clinical and pathologic features and survival of the four subtypes were
      compared. RESULTS: Using ER/PR+ and Her2- as a reference, ER/PR-, Her2- had the
      worst overall survival (hazard ratio, 1.8; 95% confidence interval [CI], 1.06
      3.2) and the worst disease-free survival (hazard ratio, 1.5; 95% CI, 0.8-3.0). In
      ER/PR+, Her2-, chemotherapy conferred significant overall and disease-free
      survival advantages. Subtype comparison revealed statistically significant
      differences in outcomes. CONCLUSION: The triple negative subtype has the worst
      overall and disease free survival. Efforts should be directed at standardization
      of current testing methods and development of more reliable and reproducible
      testing.

PMID- 19574488
TI  - Inclusion bodies in tick-borne diseases diagnosed in patients from northern
      Wisconsin.

PMID- 19574487
TI  - Updated classification system for proximal humeral fractures.
AB  - Proximal humeral fractures can restrict daily activities and, therefore, deserve
      efficient diagnoses that minimize complications and sequels. For good diagnosis
      and treatment, patient characteristics, variability in the forms of the fractures
      presented, and the technical difficulties in achieving fair results with surgical
      treatment should all be taken into account. Current classification systems for
      these fractures are based on anatomical and pathological principles, and not on
      systematic image reading. These fractures can appear in many different forms,
      with many characteristics that must be identified. However, many current
      classification systems lack good reliability, both inter-observer and intra
      observer for different image types. A new approach to image reading, following a
      well-designed set and sequence of variables to check, is needed. We previously
      reported such an image reading system. In the present study, we report a
      classification system based on this image reading system. Here we define 21
      fracture characteristics and apply them along with classical Codman approaches to
      classify fractures. We base this novel classification system for classifying
      proximal humeral fractures on a review of scientific literature and improvements
      to our image reading protocol. Patient status, fracture characteristics and
      surgeon circumstances have been important issues in developing this system.

PMID- 19574489
TI  - Metastatic virilizing adrenocortical carcinoma: a rare case of cure with surgery
      and mitotane therapy.
AB  - A 57-year-old white woman with metastases to lungs and liver from virilizing
      adrenocortical carcinoma (ACC) was treated with radical nephroadrenalectomy
      followed by oral mitotane 3 to 6 g/day for 5 months. She developed complete
      response and remained free of disease for more than 25 years. Here we present the
      case and review the literature. ACC is a rare tumor and may occur at any age.
      About 60% are functional tumors with hormonal secretions and clinical
      manifestations due to specific hormone secretions: Cushing's syndrome due to
      cortisone, virilizing tumor due to androgens, feminizing tumor due to estrogens,
      or hypertension due to aldosterone. Stage I and II disease is curable with
      surgery. Stage III and IV disease may benefit from mitotane orally with gradual
      adjustment of the dosage to a tolerable level. Plasma mitotane level at 14 to 20
      g/L results in optimal response both in hormonal secretion and symptom control,
      as well as tumor regression. Addition of chemotherapy (streptozotocin or a
      combination of etoposide, cisplatin and doxorubicin) to mitotane also produced
      responses along with increased survival among responders. An international study
      has been started by randomizing between two of the above combinations by the
      Collaborative Group for Adrenocortical Carcinoma Treatment.

PMID- 19574490
TI  - Adipose-derived stem cells are an effective cell candidate for treatment of heart
      failure: an MR imaging study of rat hearts.
AB  - This study assessed the potential therapeutic efficacy of adipose-derived stem
      cells (ASCs) on infarcted hearts. Myocardial infarction was induced in rat hearts
      by occlusion of the left anterior descending artery (LAD). One week after LAD
      occlusion, the rats were divided into three groups and subjected to
      transplantation of ASCs or transplantation of cell culture medium (CCM) or
      remained untreated. During a 1-mo recovery period, magnetic resonance imaging
      showed that the ASC-treated hearts had a significantly greater left ventricular
      (LV) ejection fraction and LV wall thickening than did the CCM-treated and
      untreated hearts. The capillary density in infarct border zone was significantly
      higher in the ASC-treated hearts than in the CCM-treated and untreated hearts.
      However, only 0.5% of the ASCs recovered from the ASC-treated hearts were stained
      positive for cardiac-specific fibril proteins. It was also found that ASCs under
      a normal culture condition secreted three cardiac protective growth factors:
      vascular endothelial growth factor, hepatocyte growth factor, and insulin-like
      growth factor-1. Results of this study suggest that ASCs were able to improve
      cardiac function of infarcted rat hearts. Paracrine effect may be the mechanism
      underlying the improved cardiac function and increased capillary density.

PMID- 19574491
TI  - Hemoglobin vesicles improve wound healing and tissue survival in critically
      ischemic skin in mice.
AB  - Local hypoxia, as due to trauma, surgery, or arterial occlusive disease, may
      severely jeopardize the survival of the affected tissue and its wound-healing
      capacity. Initially developed to replace blood transfusions, artificial oxygen
      carriers have emerged as oxygen therapeutics in such conditions. The aim of this
      study was to target primary wound healing and survival in critically ischemic
      skin by the systemic application of left-shifted liposomal hemoglobin vesicles
      (HbVs). This was tested in bilateral, cranially based dorsal skin flaps in mice
      treated with a HbV solution with an oxygen affinity that was increased to a P(50)
      (partial oxygen tension at which the hemoglobin becomes 50% saturated with
      oxygen) of 9 mmHg. Twenty percent of the total blood volume of the HbV solution
      was injected immediately and 24 h after surgery. On the first postoperative day,
      oxygen saturation in the critically ischemic middle flap portions was increased
      from 23% (untreated control) to 39% in the HbV-treated animals (P < 0.05). Six
      days postoperatively, flap tissue survival was increased from 33% (control) to
      57% (P < 0.01) and primary healing of the ischemic wound margins from 6.6 to 12.7
      mm (P < 0.05) after HbV injection. In addition, higher capillary counts and
      endothelial nitric oxide synthase expression (both P < 0.01) were found in the
      immunostained flap tissue. We conclude that left-shifted HbVs may ameliorate the
      survival and primary wound healing in critically ischemic skin, possibly mediated
      by endothelial nitric oxide synthase-induced neovascularization.

PMID- 19574492
TI  - Evaluation of a pre-existing, 3-year household water treatment and handwashing
      intervention in rural Guatemala.
AB  - BACKGROUND: The promotion of household water treatment and handwashing with soap
      has led to large reductions in child diarrhoea in randomized efficacy trials.
      Currently, we know little about the health effectiveness of behaviour-based water
      and hygiene interventions after the conclusion of intervention activities.
      METHODS: We present an extension of previously published design (propensity score
      matching) and analysis (targeted maximum likelihood estimation) methods to
      evaluate the behavioural and health impacts of a pre-existing but non-randomized
      intervention (a 3-year, combined household water treatment and handwashing
      campaign in rural Guatemala). Six months after the intervention, we conducted a
      cross-sectional cohort study in 30 villages (15 intervention and 15 control) that
      included 600 households, and 929 children <5 years of age. RESULTS: The study
      design created a sample of intervention and control villages that were comparable
      across more than 30 potentially confounding characteristics. The intervention led
      to modest gains in confirmed water treatment behaviour [risk difference = 0.05,
      95% confidence interval (CI) 0.02-0.09]. We found, however, no difference between
      the intervention and control villages in self-reported handwashing behaviour,
      spot-check hygiene conditions, or the prevalence of child diarrhoea, clinical
      acute lower respiratory infections or child growth. CONCLUSIONS: To our knowledge
      this is the first post-intervention follow-up study of a combined household water
      treatment and handwashing behaviour change intervention, and the first post
      intervention follow-up of either intervention type to include child health
      measurement. The lack of child health impacts is consistent with unsustained
      behaviour adoption. Our findings highlight the difficulty of implementing
      behaviour-based household water treatment and handwashing outside of intensive
      efficacy trials.

PMID- 19574493
TI  - Focal neuronal gigantism: a rare complication of therapeutic radiation.
AB  - Radiation therapy, a mainstay in the treatment of many brain tumors, results in a
      variety of well-documented acute and chronic complications. Isolated cortical
      damage following irradiation represents an extremely rare delayed therapeutic
      complication, described only twice in the medical literature. We report this rare
      delayed complication in a patient following treatment of a right frontal
      anaplastic oligodendroglioma.

PMID- 19574494
TI  - Preservation of knowledge, part 2: digital archives.

PMID- 19574495
TI  - MR angiography follow-up of aneurysms treated with coils: is there a need for the
      use of gadolinium?

PMID- 19574496
TI  - Diffusion tensor imaging of the subcortical auditory tract in subjects with
      congenital cochlear nerve deficiency.
AB  - BACKGROUND AND PURPOSE: Cochlear nerve deficiency (CND), including aplasia and
      hypoplasia, is a rare cause of congenital hearing loss. The purpose of this study
      was to evaluate the neuronal integrity of the subcortical auditory pathway in
      subjects with CND by diffusion tensor MR imaging (DTI). MATERIALS AND METHODS:
      Twelve subjects with unilateral congenital CND were included in this prospective
      study. Twelve normal-hearing subjects served as controls. DTIs were acquired from
      these subjects on a 3T MR imaging scanner. Several indices including axial
      diffusivity (lambda( ||)), radial diffusivity (lambda( perpendicular)), mean
      diffusivity (MD), and fractional anisotropy (FA) along the auditory pathway were
      extracted. Two regions of interest were selected bilaterally for evaluation: the
      lateral lemniscus (LL) and inferior colliculus (IC). The mean values of lambda(
      ||), lambda( perpendicular), MD, and FA at both regions of interest were compared
      between the ipsilateral and contralateral sides of subjects with CND with those
      in the control group. RESULTS: Significant decrease of FA and increase of MD on
      both the ipsilateral and contralateral sides of patients with CND as compared
      with normal subjects in both LL and IC were found. The decrease of FA was due to
      the increase of lambda( perpendicular), whereas lambda( ||) remained unchanged.
      CONCLUSIONS: The maintained axial diffusion implied that the orientation of
      neural fibers along the subcortical auditory pathway in subjects with unilateral
      CND is intact. However, the reduction in FA and increase in lambda(
      perpendicular) on both the ipsilateral and contralateral sides might be
      attributed to axonal loss and/or demyelination of the subcortical auditory tract
      in these subjects.

PMID- 19574497
TI  - Maturation of thalamic radiations between 34 and 41 weeks' gestation: a combined
      voxel-based study and probabilistic tractography with diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate brain maturation along
      gestational age with diffusion tensor imaging in healthy preterm and term
      neonates. Therefore, a voxel-based study of fractional anisotropy (FA) and mean
      diffusivity (D(av)) was performed to reveal the brain regions experiencing
      microstructural changes with age. With tractography, the authors intended to
      identify which fiber tracts were included in these significant voxels. MATERIALS
      AND METHODS: There were 22 healthy preterm and 6 healthy term infants who
      underwent MR imaging between 34 and 41 weeks of gestation. A statistical
      parametric approach was used to evidence the effect of age on regional
      distribution of FA and D(av) values. The fiber tracts suspected to be included in
      the significant clusters of voxels were identified with neuroanatomy and
      tractography atlases, reconstructed with probabilistic tractography, and
      superimposed on the parametric maps. RESULTS: Parametric analysis showed that FA
      increases with age in the subcortical projections from the frontal (motor and
      premotor areas) and parietal cortices, the centrum semiovale, the anterior and
      posterior arms of the internal capsules, the optic radiations, the corpus
      callosum, and the thalami (P < .05, corrected). Superimposition of the parametric
      maps on tractography showed that the corticospinal tract (CST); the callosal
      radiations (CR); and the superior, anterior, and posterior thalamic radiations
      were included in the significant voxels. No statistically significant results
      were found for D(av) maps. CONCLUSIONS: These results highlight that, besides the
      already-evidenced FA increase in the CST and CR, the thalami and the thalamic
      radiations experience microstructural changes in the early development of the
      human brain.

PMID- 19574498
TI  - Symptomatic perianeurysmal edema following bare platinum embolization of a small
      unruptured cerebral aneurysm.
AB  - There is considerable interest in the development of symptomatic inflammatory
      reactions following coil embolization of cerebral aneurysms. Patients have
      experienced a range of adverse events, usually after treatment of moderately
      large aneurysms with modified "bioactive" coils. More recently, it has been
      recognized that adverse inflammatory reactions can be associated with the use of
      "nonbioactive" coils, and we present a case of symptomatic perianeurysmal edema
      after treatment of a small unruptured aneurysm with bare platinum coils.

PMID- 19574499
TI  - Identification of rare cancer driver mutations by network reconstruction.
AB  - Recent large-scale tumor resequencing studies have identified a number of
      mutations that might be involved in tumorigenesis. Analysis of the frequency of
      specific mutations across different tumors has been able to identify some, but
      not all of the mutated genes that contribute to tumor initiation and progression.
      One reason for this is that other functionally important genes are likely to be
      mutated more rarely and only in specific contexts. Thus, for example, mutation in
      one member of a collection of functionally related genes may result in the same
      net effect, and/or mutations in certain genes may be observed less frequently if
      they play functional roles in later stages of tumor development, such as
      metastasis. We modified and applied a network reconstruction and coexpression
      module identification-based approach to identify functionally related gene
      modules targeted by somatic mutations in cancer. This method was applied to
      available breast cancer, colorectal cancer, and glioblastoma sequence data, and
      identified Wnt/TGF-beta cross-talk, Wnt/VEGF signaling, and MAPK/focal adhesion
      kinase pathways as targets of rare driver mutations in breast, colorectal cancer,
      and glioblastoma, respectively. These mutations do not appear to alter genes that
      play a central role in these pathways, but rather contribute to a more refined
      shaping or "tuning" of the functioning of these pathways in such a way as to
      result in the inhibition of their tumor-suppressive signaling arms, and thereby
      conserve or enhance tumor-promoting processes.

PMID- 19574500
TI  - Impact of preinduced quadriceps fatigue on exercise response in chronic
      obstructive pulmonary disease and healthy subjects.
AB  - Exercise intolerance in chronic obstructive pulmonary disease (COPD) results from
      a complex interaction between central (ventilatory) and peripheral (limb muscles)
      components of exercise limitation. The purpose of this study was to evaluate the
      influence of quadriceps muscle fatigue on exercise tolerance and ventilatory
      response during constant-workrate cycling exercise testing (CWT) in patients with
      COPD and healthy subjects. Fifteen patients with COPD and nine age-matched
      healthy subjects performed, 7 days apart, two CWTs up to exhaustion at 80% of
      their predetermined maximal work capacity. In a randomized order, one test was
      performed with preinduced quadriceps fatigue and the other in a fresh state.
      Quadriceps fatigue was produced by electrostimulation-induced contractions and
      quantified by maximal voluntary contraction and potentiated twitch force
      (TwQ(pot)). Endurance time and ventilatory response during CWT were compared
      between fatigued and fresh state. Endurance time significantly decreased in the
      fatigued state compared with the fresh condition in COPD (356 +/- 69 s vs. 294 +/
      45 s, P < 0.05) and controls (450 +/- 74 s vs. 340 +/- 45 s, P < 0.05). Controls
      showed significantly higher ventilation and end-exercise dyspnea scores in the
      fatigued condition, whereas, in COPD, fatigue did not influence ventilation or
      dyspnea during exercise. The degree of ventilatory limitation, as expressed by
      the Ve/maximum voluntary ventilation ratio, was similar in both conditions in
      patients with COPD. We conclude that it is possible to induce quadriceps fatigue
      by local electrostimulation-induced contractions. Our findings demonstrate that
      peripheral muscle fatigue is an additional important factor, besides intense
      dyspnea, that limits exercise tolerance in COPD.

PMID- 19574501
TI  - Increased serum levels of the brain damage marker S100B after apnea in trained
      breath-hold divers: a study including respiratory and cardiovascular
      observations.
AB  - The concentration of the protein S100B in serum is used as a brain damage marker
      in various conditions. We wanted to investigate whether a voluntary, prolonged
      apnea in trained breath-hold divers resulted in an increase of S100B in serum.
      Nine trained breath-hold divers performed a protocol mimicking the procedures
      they use during breath-hold training and competition, including extensive
      preapneic hyperventilation and glossopharyngeal insufflation, in order to perform
      a maximum-duration apnea, i.e., "static apnea" (average: 335 s, range: 281-403
      s). Arterial blood samples were collected and cardiovascular variables recorded.
      Arterial partial pressures of O(2) and CO(2) (Pa(O(2)) and Pa(CO(2))) were 128
      Torr and 20 Torr, respectively, at the start of apnea. The degree of asphyxia at
      the end of apnea was considerable, with Pa(O(2)) and Pa(CO(2)) reaching 28 Torr
      and 45 Torr, respectively. The concentration of S100B in serum transiently
      increased from 0.066 microg/l at the start of apnea to 0.083 microg/l after the
      apnea (P < 0.05). The increase in S100B is attributed to the asphyxia or to other
      physiological responses to apnea, for example, increased blood pressure, and
      probably indicates a temporary opening of the blood-brain barrier. It is not
      possible to conclude that the observed increase in S100B levels in serum after a
      maximal-duration apnea reflects a serious injury to the brain, although the
      results raise concerns considering negative long-term effects. At the least, the
      results indicate that prolonged, voluntary apnea affects the integrity of the
      central nervous system and do not preclude cumulative effects.

PMID- 19574502
TI  - Higher intramuscular triacylglycerol in women does not impair insulin sensitivity
      and proximal insulin signaling.
AB  - Women have been shown to have higher muscle triacylglycerol (IMTG) levels than
      men and could therefore be expected to have lower insulin sensitivity than men,
      since previous studies have linked high IMTG to decreased insulin sensitivity.
      Therefore, insulin sensitivity of whole body and leg glucose uptake was studied
      in 9 women in the follicular phase and 8 men on a controlled diet and matched for
      maximal oxygen uptake per kilogram of lean body mass and habitual activity level.
      A 47% higher (P < 0.05) IMTG level was found in women than in men, and, at the
      same time, women also displayed 22% higher whole body insulin sensitivity (P <
      0.05) and 29% higher insulin-stimulated leg glucose uptake (P = 0.05) during an
      euglycemic-hyperinsulinemic (approximately 70 microU/ml) clamp compared with
      matched male subjects. The higher insulin sensitivity in women could not be
      explained by higher expression of muscle glucose transporter GLUT4, insulin
      receptor, or Akt expression or by the ability of insulin to stimulate Akt
      Thr(308) or Akt Ser(473) phosphorylation. However, a 30% higher (P < 0.05)
      capillary density and 31% more type 1 muscle fiber expressed per area in the
      vastus lateralis muscle were noted in women than in matched men. It is concluded
      that despite 47% higher IMTG levels in women in the follicular phase, whole body
      as well as leg insulin sensitivity are higher than in matched men. This was not
      explained by sex differences in proximal insulin signaling in women. In women, it
      seems that a high capillary density and type 1 muscle fiber expression may be
      important for insulin action.

PMID- 19574503
TI  - Prior exercise improves survival, infarct healing, and left ventricular function
      after myocardial infarction.
AB  - We investigated the effects of voluntary wheel running before an acute myocardial
      infarction (MI) on survival, left ventricular (LV) remodeling and dysfunction and
      whether exercise before and after MI provides superior protection compared with
      either exercise intervention alone. After 2 wk of voluntary wheel running or
      sedentary housing, MI was induced in C57Bl/6 mice, after which exercise was
      stopped (EX-MI-SED and SED-MI-SED groups, where EX is exercise and SED is
      sedentary) or continued (EX-MI-EX and SED-MI-EX groups) for a period of 8 wk.
      Exercise after MI in SED-MI-EX mice had no effect on survival, the area of
      infarction, and global LV remodeling, but attenuated fibrosis and apoptosis in
      the remote myocardium and blunted LV dysfunction and pulmonary congestion
      compared with SED-MI-SED mice. Exercise before MI in both EX-MI-SED and EX-MI-EX
      mice decreased post-MI mortality compared with both SED-MI-SED and SED-MI-EX
      mice. Furthermore, in both pre-MI exercise groups, the infarct area was thicker,
      whereas interstitial fibrosis and apoptosis in the remote LV myocardium were
      blunted. In contrast, the ameliorating effects of either pre-MI or post-MI
      exercise alone on LV dysfunction were lost in EX-MI-EX mice, which may in part be
      related to the increased daily exercise distance in the first week post-MI in EX
      MI-EX versus SED-MI-EX mice. In conclusion, exercise before or after MI blunted
      LV dysfunction, whereas only exercise before MI improved survival. These findings
      suggest that even when regular physical activity fails to prevent an acute MI, it
      can still act to improve cardiac function and survival after MI.

PMID- 19574504
TI  - Transient influence of end-tidal carbon dioxide tension on the postural restraint
      in cerebral perfusion.
AB  - In the upright position, cerebral blood flow is reduced, maybe because arterial
      carbon dioxide partial pressure (Pa(CO(2))) decreases. We evaluated the time
      dependent influence of a reduction in Pa(CO(2)), as indicated by the end-tidal
      Pco(2) tension (Pet(CO(2))), on cerebral perfusion during head-up tilt. Mean
      arterial pressure, cardiac output, middle cerebral artery mean flow velocity (MCA
      V(mean)), and dynamic cerebral autoregulation at supine rest and 70 degrees head
      up tilt were determined during free breathing and with Pet(CO(2)) clamped to the
      supine level. The postural changes in central hemodynamic variables were
      equivalent, and the cerebrovascular autoregulatory capacity was not significantly
      affected by tilt or by clamping Pet(CO(2)). In the first minute of tilt, the
      decline in MCA V(mean) (10 +/- 4 vs. 3 +/- 4 cm/s; mean +/- SE; P < 0.05) and
      Pet(CO(2)) (6.8 +/- 4.3 vs. 1.7 +/- 1.6 Torr; P < 0.05) was larger during
      spontaneous breathing than during isocapnic tilt. However, after 2 min in the
      head-up position, the reduction in MCA V(mean) was similar (7 +/- 5 vs. 6 +/- 3
      cm/s), although the spontaneous decline in Pet(CO(2)) was maintained (P < 0.05
      vs. isocapnic tilt). These results suggest that the potential contribution of
      Pa(CO(2)) to the postural reduction in MCA V(mean) is transient, leaving the
      mechanisms for the sustained restrain in MCA V(mean) to be identified.

PMID- 19574505
TI  - Molecular control of circadian metabolic rhythms.
AB  - Circadian metabolic rhythms are fundamental to the control of nutrient and energy
      homeostasis, as well as the pathogenesis of metabolic disease, such as obesity,
      lipid disorders, and type 2 diabetes. This temporal organization of tissue
      metabolism is coordinated through reciprocal cross talk between the biological
      timing system and the metabolic regulatory networks. In this review, we discuss
      the signaling mechanisms that serve to couple metabolic regulation to the
      circadian pacemaker, in particular the role of the peroxisome proliferator
      activated receptor-gamma coactivator-1 transcriptional coactivators in
      integrating clock and energy metabolism.

PMID- 19574506
TI  - Hormone therapy attenuates exercise-induced skeletal muscle damage in
      postmenopausal women.
AB  - Hormone therapy (HT) is a potential treatment to relieve symptoms of menopause
      and prevent the onset of disease such as osteoporosis in postmenopausal women. We
      evaluated changes in markers of exercise-induced skeletal muscle damage and
      inflammation [serum creatine kinase (CK), serum lactate dehydrogenase (LDH), and
      skeletal muscle mRNA expression of IL-6, IL-8, IL-15, and TNF-alpha] in
      postmenopausal women after a high-intensity resistance exercise bout. Fourteen
      postmenopausal women were divided into two groups: women not using HT (control; n
      = 6, 59 +/- 4 yr, 63 +/- 17 kg) and women using traditional HT (HT; n = 8, 59 +/-
      4 yr, 89 +/- 24 kg). Both groups performed 10 sets of 10 maximal eccentric
      repetitions of single-leg extension on the Cybex dynamometer at 60 degrees /s
      with 20-s rest periods between sets. Muscle biopsies of the vastus lateralis were
      obtained from the exercised leg at baseline and 4 h after the exercise bout. Gene
      expression was determined by RT-PCR for IL-6, IL-8, IL-15, and TNF-alpha. Blood
      draws were performed at baseline and 3 days after exercise to measure CK and LDH.
      Independent t-tests were performed to test group differences (control vs. HT). A
      probability level of P <or= 0.05 was used to determine statistical significance.
      We observed significantly greater changes in mRNA expression of IL-6, IL-8, IL
      15, and TNF-alpha (P <or= 0.01) in the control group compared with the HT group
      after the exercise bout. CK and LDH levels were significantly greater after
      exercise (P <or= 0.01) in the control group. Postmenopausal women not using HT
      experienced greater muscle damage after maximal eccentric exercise, indicating a
      possible protective effect of HT against exercise-induced skeletal muscle damage.

PMID- 19574507
TI  - Vestibular evoked myogenic potentials evoked by brief interaural head
      acceleration: properties and possible origin.
AB  - The vestibular system responds to head acceleration by producing compensatory
      reflexes in the eyes and postural muscles. In this study, we investigated the
      effect of brief interaural acceleration on the vestibular evoked myogenic
      potential (VEMP) in 10 normal subjects and 10 patients with bilateral (bVL) or
      unilateral vestibular loss (uVL). The stimuli were delivered with a handheld
      minishaker and tendon hammer over the mastoid and produced relatively pure
      interaural head acceleration with little rotation (mean peak acceleration: 0.14 g
      at 3.3 ms). VEMPs were recorded from the neck muscles and were characterized in
      normal subjects by a positive/negative potential ipsilateral to the stimulated
      side (peak latencies: 15.1 and 22.6 ms) and a positive response contralaterally
      (20.3 ms), which was sometimes preceded by a negativity (14.5 ms). These peaks
      were absent in patients with bVL, confirming their vestibular dependence. In the
      patients with uVL, medial acceleration of the intact ear produced bilateral
      responses, an initial positivity on the intact side, and a negativity on the
      affected side, whereas lateral acceleration produced only a late positivity on
      the intact side. As the acceleration was primarily in the horizontal plane, it is
      likely to have activated utricular receptors. Consistent with this, we found that
      VEMPs are very sensitive to the direction of head acceleration and have features
      consistent with the utriculocollic projections demonstrated in animals.

PMID- 19574508
TI  - Gold standards for scientists who are conducting animal-based exercise studies.

PMID- 19574509
TI  - Directors of medical student education in psychiatry and recruitment into
      psychiatry: an ethical issue?

PMID- 19574510
TI  - ADMSEP Position Statement on Recruitment.

PMID- 19574511
TI  - Training psychiatrists in nonpsychiatric medicine: what do our patients and our
      profession need?

PMID- 19574512
TI  - Planning the future mental health workforce: with progress on coverage, what role
      will psychiatrists play?

PMID- 19574514
TI  - The perceptions and habits of alcohol consumption and smoking among Canadian
      medical students.
AB  - OBJECTIVE: The authors aim to quantify the extent, and to assess student
      perception, of alcohol and tobacco use among medical students at the University
      of Calgary, and the relationship of these attitudes to problem drinking
      (according to the CAGE questionnaire). METHODS: A questionnaire was distributed
      to first-, second-, and third-year medical students attending the University of
      Calgary medical school. RESULTS: Of the 327 students enrolled, 175 of students
      responded to the questionnaire. Six percent of the students currently smoke while
      24% of students reported cigarette smoking at some point in their life. Eighty
      six percent of students currently drink, with a majority drinking fewer than 11
      drinks per week. Fifteen percent of students were at an increased risk for
      problem drinking according to the CAGE questionnaire. An increased risk for
      problem drinking was significantly related to believing more strongly that
      getting drunk is acceptable on occasion and less strongly that increased alcohol
      has many negative health consequences, as well as feeling less in control of
      alcohol consumption. CONCLUSION: Medical students at the University of Calgary
      consume less alcohol and cigarettes than a comparable population. However, a high
      proportion of students are at risk for alcohol abuse according to the CAGE
      questionnaire. The results of this study suggest that although the quantity of
      alcohol consumed is not a substantial concern at this time, students might be at
      risk for future alcohol abuse.

PMID- 19574515
TI  - Balint-style case discussion groups in psychiatric training: an evaluation.
AB  - OBJECTIVES: The authors aim to identify any benefits or limitations of
      psychiatric residents attending a Balint-style case discussion group, to explore
      those experiences, to study the process of the learning experience, and to
      identify potential educational implications. METHODS: Seventeen psychiatric
      residents and counselors completing two parallel case discussion groups at a U.K.
      psychotherapy service were given in-depth interviews about their experiences of
      this training. Interview transcripts were analyzed using qualitative methodology.
      RESULTS: The groups were anxiety provoking; most participants were able to
      progressively accommodate to and benefit from the psychological learning process,
      but some struggled to adapt. CONCLUSION: Basic psychological competency and the
      awareness of the self in relation to the patient can be fostered through
      attendance at a case discussion group. With some limitations, Balint groups
      continue to be a useful way of introducing young psychiatrists to psychological
      processes.

PMID- 19574516
TI  - Student experiences with competency domains during a psychiatry clerkship.
AB  - OBJECTIVES: The authors reviewed medical student encounters during 3 years of a
      required psychiatry clerkship that were recorded on a web-based system of six
      broad competency domains (similar to ACGME-recommended domains). These were used
      to determine diagnoses of patients seen, clinical skills practiced, and
      experiences in interpersonal and communications skills, professionalism, practice
      based learning and improvement, and system-based practice. The authors aim to
      understand how students are learning and growing in these domains and to modify
      the clerkship in an ongoing manner. METHODS: Data were collected from the
      Dartmouth Medical Encounter Documentation System (DMEDS) for all student
      encounters in required third-year psychiatry clerkships during academic years
      2004-2007, in which students had intensive involvement in patient care. RESULTS:
      One hundred seventy three students reported a total of 4,676 patient encounters,
      averaging 27.2 encounters per student and 1.8 psychiatric diagnoses per patient.
      Students met "learning targets" for anxiety disorder, bipolar affective disorder,
      depression, personality disorder (borderline), posttraumatic stress disorder,
      psychosis, schizophrenia, and substance abuse (alcohol), but not for disorders
      more likely seen in outpatient settings. For the 10 counseling skills learning
      targets, students only met those for family issues. In the four "newer"
      competency domains, students reported struggling with issues in 0.3% to 12.6% of
      encounters. Students documented being challenged by professionalism issues most
      often and recorded examples of how these competencies played out for them during
      the clerkship. CONCLUSION: Use of a required web-based medical encounter
      reporting system for student-patient-faculty encounters during a psychiatry
      clerkship can be of significant value in assessing what students are seeing,
      doing, and learning on this required third-year experience. The results provide
      helpful current information to the clerkship director and data that help the
      director modify the clerkship on an ongoing basis to better meet students'
      educational needs.

PMID- 19574517
TI  - The effect of clinical clerkship on students' attitudes toward psychiatry in
      Karachi, Pakistan.
AB  - OBJECTIVE: Attitudes of medical students toward a specialty is strongly related
      to their future choice of specialty. In developing countries like Pakistan, where
      there is a shortage of psychiatrists, there is a need to assess the effect of
      exposure to psychiatry on medical students. METHODS: The authors conducted a
      survey of fourth-year medical students at Aga Khan University in Karachi,
      Pakistan. RESULTS: Psychiatry clerkship had an overall positive attitude toward
      psychiatric illness, patients, and psychiatrists, but no effect on students'
      choice of psychiatry as a career. CONCLUSION: Psychiatry teaching needs to be
      made more relevant to the rest of the medical curricula. This may improve
      students' interest and their future choice of psychiatry as an area of
      specialization.

PMID- 19574518
TI  - Ensuring research competency in psychiatric residency training.
AB  - OBJECTIVE: This article discusses the importance of research training in
      psychiatric residency programs and makes recommendations for enhancement.
      METHODS: The authors examine the literature detailing the shortage of
      psychiatrist-researchers and the limitations of research training during
      residency. The authors then describe the Psychiatrists Acquiring Research
      Training (PART) program at Beth Israel Medical Center that attempts to address
      this problem. Data collected on resident scholarly activity, including
      publications and presentations, is presented. RESULTS: Since its inception, all
      scholarly activities have increased under the PART program. The 89 residents,
      followed over 5 academic years, co-authored 32 publications, gave 56
      presentations, and received prestigious honors such as NIMH fellowships and
      national research awards. CONCLUSION: Residents' participation in research has
      been advanced through participation in PART. Ensuring research competency among
      all psychiatrists is crucial to providing the best science-based care; PART
      represents a cost-effective way to integrate research training with psychiatric
      residency. The authors also discuss opportunities and obstacles to developing
      research programs as part of psychiatric residency training.

PMID- 19574520
TI  - Integrating statistical and clinical research elements in intervention-related
      grant applications: summary from an NIMH workshop.
AB  - OBJECTIVE: The authors summarize points for consideration generated in a National
      Institute of Mental Health (NIMH) workshop convened to provide an opportunity for
      reviewers from different disciplines-specifically clinical researchers and
      statisticians-to discuss how their differing and complementary expertise can be
      well integrated in the review of intervention-related grant applications.
      METHODS: A 1-day workshop was convened in October, 2004. The workshop featured
      panel presentations on key topics followed by interactive discussion. This
      article summarizes the workshop and subsequent discussions, which centered on
      topics including weighting the statistics/data analysis elements of an
      application in the assessment of the application's overall merit; the level of
      statistical sophistication appropriate to different stages of research and for
      different funding mechanisms; some key considerations in the design and analysis
      portions of applications; appropriate statistical methods for addressing
      essential questions posed by an application; and the role of the statistician in
      the application's development, study conduct, and interpretation and
      dissemination of results. RESULTS: A number of key elements crucial to the
      construction and review of grant applications were identified. It was
      acknowledged that intervention-related studies unavoidably involve trade-offs.
      Reviewers are helped when applications acknowledge such trade-offs and provide
      good rationale for their choices. Clear linkage among the design, aims,
      hypotheses, and data analysis plan and avoidance of disconnections among these
      elements also strengthens applications. CONCLUSION: The authors identify multiple
      points to consider when constructing intervention-related grant applications. The
      points are presented here as questions and do not reflect institute policy or
      comprise a list of best practices, but rather represent points for consideration.

PMID- 19574522
TI  - Procedural challenges in international collaborative research.
AB  - OBJECTIVE: Knowledge of the procedural requirements for international research is
      not widely disseminated to investigators involved in the administration of a
      federal grant with a foreign component. The purpose of this article is to
      highlight the major challenges in administrative, procedural, and equipment
      management aspects of grant implementation when federal funding is involved in
      international collaborative research. METHODS: The author describes the
      procedural requirements for international research from the time of priority
      score receipt to the implementation of the grant. RESULTS: There is tremendous
      promise for rewarding experiences in international research projects due to the
      collaboration, mutual learning, and cultural bridging that intrinsically occur.
      However, there are also inherent cross-national procedural requirements that can
      be demanding in time and effort for the investigator and other stakeholders of
      the grant. CONCLUSIONS: It is hoped that awareness of these difficulties and
      demystification of the process for future investigators can minimize the
      potential encumbrances in such international research.

PMID- 19574524
TI  - Understanding the challenges of integrating scientists and clinical teachers in
      psychiatry education: findings from an innovative faculty development program.
AB  - OBJECTIVE: Medical schools and departments of psychiatry around the world face
      challenges in integrating science with clinical teaching. This project was
      designed to identify attitudes toward the integration of science in clinical
      teaching and address barriers to collaboration between scientists and clinical
      teachers. METHODS: The authors explored the interactions of 20 faculty members
      (10 scientists and 10 clinical teachers) taking part in a 1-year structured
      faculty development program, based on a partnership model, designed to encourage
      collaborative interaction between scientists and clinical teachers. Data were
      collected before, during, and after the program using participant observations,
      surveys, participant diaries, and focus groups. Qualitative data were analyzed
      iteratively using the method of meaning condensation, and further informed with
      descriptive statistics generated from the pre- and postsurveys. RESULTS:
      Scientists and clinicians were strikingly unfamiliar with each other's
      worldviews, work experiences, professional expectations, and approaches to
      teaching. The partnership model appeared to influence integration at a social
      level, and led to the identification of departmental structural barriers that
      aggravate the divide between scientists and clinical teachers. Issues related to
      the integration of social scientists in particular emerged. CONCLUSION: Creating
      a formal program to encourage interaction of scientists and clinical teachers
      provided a forum for identifying some of the barriers associated with the
      collaboration of scientists and clinical teachers. Our data point to directions
      for organizational structures and faculty development that support the
      integration of scientists from a wide range of disciplines with their clinical
      faculty colleagues.

PMID- 19574525
TI  - A progress report on a department of psychiatry faculty practice plan designed to
      reward educational and research productivity.
AB  - OBJECTIVE: The authors provide a progress report on a faculty practice plan that
      assigns a monetary value to administrative duties, teaching, scholarship,
      community service, and research. METHODS: Modifications to the original plan are
      described and quantifiable results in the areas of scholarship and research are
      summarized. RESULTS: During a 4-year period reported, the total direct costs of
      all grants increased 40% and the total number of publications increased 108%
      during this same time frame. CONCLUSION: The authors believe that a practice plan
      which assigns a monetary value to administrative duties, teaching, scholarship,
      community service, and research can incentivize faculty to be successful in each
      of these areas.

PMID- 19574526
TI  - Introducing psychiatrists to qualitative research: a guide for instructors.

PMID- 19574523
TI  - An institutional postdoctoral research training program: predictors of
      publication rate and federal funding success of its graduates.
AB  - OBJECTIVE: The National Institute of Mental Health funds institutional National
      Research Service Awards (NRSA) to provide postdoctoral research training. While
      peer-reviewed publications are the most common outcome measure utilized, there
      has been little discussion of how publications should be counted or what factors
      impact the long-term publication rates of trainees in these programs. METHODS:
      The authors reviewed current curricula vitae from 92 graduates of an
      institutional NRSA and from the faculty mentors of that program to assess
      publications through 2005. Publications were weighted based on peer versus non
      peer-reviewed and authorship position. Trainee and mentor factors were assessed
      for their impact on publication rates and on becoming principal investigators of
      larger scale federal grants such as a National Institutes of Health (NIH) R01.
      RESULTS: Weighted publication scores correlate with total publication rates at
      such a high rate that the two scores can be used interchangeably. Forty-three
      percent of graduates average at least one publication per year after completing
      the postdoctoral program; 20% were listed as an independent investigator on a
      larger federal grant. The number of publications published during postdoctoral
      training and additional funded training beyond that provided by the institutional
      NRSA are correlated with increased posttraining program publication rates; other
      factors including gender, terminal degree, number of publications prior to
      postdoctoral training, and mentor variables had no significant impact. Additional
      funded training, male gender, and increased time since completion of the training
      are associated with increased likelihood of larger grant federal funding.
      CONCLUSION: Weighting publications by whether they were peer-reviewed and by
      authorship position appears to have little benefit over a simple counting of the
      number of publications. Publication during research training and the pursuit of
      funding for additional individual research training may be appropriate short-term
      goals within an institutional research training program.

PMID- 19574529
TI  - Educational research questions and study design.

PMID- 19574528
TI  - How to write an NIH R13 conference grant application.
AB  - OBJECTIVE: The purpose of this article is to provide recommendations for writing
      a successful R13 conference grant proposal for the National Institutes of Health
      (NIH). METHODS: The authors reviewed successful NIH conference grant proposal
      abstracts. They also reflect on their own experience in writing an NIH conference
      grant proposal and implementing a successful annual conference on research
      methods in the area of psychological trauma. RESULTS: The key to a strong
      proposal is linkage among all of its sections, from the specific aims to the
      budget. The specific aims should be justified by the need for the conference and
      articulated in the background and significance section, and the aims, in turn,
      should drive the content and format of the conference. CONCLUSION: Conferences
      can be an important way to promote NIH scientific goals, by disseminating new
      findings, facilitating collaborations, and stimulating new lines of research.

PMID- 19574530
TI  - Teaching psychiatric residents research literacy: use of existing epidemiological
      databases.

PMID- 19574532
TI  - Role of gremlin in the lung: development and disease.
AB  - Gremlin is an extracellular glycoprotein that was first identified over a decade
      ago through its important role in embryonic development, in which it acts as an
      antagonist of bone morphogenetic protein actions. It plays a critical role in the
      development of normal airways and the pulmonary circulation in the embryo. More
      recently, considerable evidence has been presented for a role for gremlin in the
      pathogenesis of lung diseases, particularly pulmonary hypertension and idiopathic
      pulmonary fibrosis. The purpose of this article is to review this evidence,
      consider the potential mechanisms and multicellular actions by which gremlin
      contributes to disease pathogenesis, and suggest future avenues of research.

PMID- 19574531
TI  - Mechanisms of alveolar epithelial translocation of a defined population of
      nanoparticles.
AB  - To explore mechanisms of nanoparticle interactions with and trafficking across
      lung alveolar epithelium, we utilized primary rat alveolar epithelial cell
      monolayers (RAECMs) and an artificial lipid bilayer on filter model (ALBF).
      Trafficking rates of fluorescently labeled polystyrene nanoparticles (PNPs; 20
      and 100 nm, carboxylate (negatively charged) or amidine (positively charged)
      modified) in the apical-to-basolateral direction under various experimental
      conditions were measured. Using confocal laser scanning microscopy, we
      investigated PNP colocalization with early endosome antigen-1, caveolin-1,
      clathrin heavy chain, cholera toxin B, and wheat germ agglutinin. Leakage of 5
      carboxyfluorescein diacetate from RAECMs, and trafficking of (22)Na and (14)C
      mannitol across ALBF, were measured in the presence and absence of PNPs. Results
      showed that trafficking of positively charged PNPs was 20-40 times that of
      negatively charged PNPs across both RAECMs and ALBF, whereas translocation of
      PNPs across RAECMs was 2-3 times faster than that across ALBF. Trafficking rates
      of PNPs across RAECMs did not change in the presence of EGTA (which decreased
      transepithelial electrical resistance to zero) or inhibitors of endocytosis.
      Confocal laser scanning microscopy revealed no intracellular colocalization of
      PNPs with early endosome antigen-1, caveolin-1, clathrin heavy chain, cholera
      toxin B, or wheat germ agglutinin. Leakage of 5-carboxyfluorescein diacetate from
      alveolar epithelial cells, and sodium ion and mannitol flux across ALBF, were not
      different in the presence or absence of PNPs. These data indicate that PNPs
      translocate primarily transcellularly across RAECMs, but not via known major
      endocytic pathways, and suggest that such translocation may take place by
      diffusion of PNPs through the lipid bilayer of cell plasma membranes.

PMID- 19574533
TI  - Macrophages: regulators of sex differences in asthma?
AB  - Females are more susceptible to development of asthma than are males. In a mouse
      model of ovalbumin-induced airway inflammation, with aggravated disease in
      females compared with males, we studied interactions between immune and resident
      lung cells during asthma development to elucidate which processes are affected by
      sex. We studied numbers of regulatory T cells (Tregs), effector T cells, myeloid
      dendritic cells (mDCs), and alternatively activated macrophages (AAMPhi), and
      their functional capabilities. Male and female mice had comparable Treg numbers
      in lung tissue and comparable Treg function, but effector T cells had expanded to
      a greater extent in lungs of females after ovalbumin exposure. This difference in
      T cell expansion was therefore not the result of lack of Treg control, but
      appeared to be driven by a greater number of inflammatory mDCs migrating from the
      lungs to lymph nodes in females. Resident lung cells can influence mDC migration,
      and AAMPhi in lung tissue were found to be involved. Artificially elevating the
      number of AAMPhi in lung tissue increased the migration of mDCs and airway
      inflammation. We found greater numbers of AAMPhi in female lungs than in males;
      we therefore postulate that AAMPhi are involved in increased airway inflammation
      found in female mice.

PMID- 19574534
TI  - Myristoylated alanine-rich C-kinase substrate (MARCKS) protein regulation of
      human neutrophil migration.
AB  - Neutrophil migration into infected tissues is essential for host defense, but
      products of activated neutrophils can be quite damaging to host cells. Neutrophil
      influx into the lung and airways and resultant inflammation characterizes
      diseases such as chronic obstructive pulmonary disease, bronchiectasis, and
      cystic fibrosis. To migrate, neutrophils must reorganize the actin cytoskeleton
      to establish a leading edge pseudopod and a trailing edge uropod. The actin
      binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) has been
      shown to bind and cross-link actin in a variety of cell types and to co-localize
      with F-actin in the leading edge lamellipodium of migrating fibroblasts. The
      hypothesis that MARCKS has a role in the regulation of neutrophil migration was
      tested using a cell-permeant peptide derived from the MARCKS myristoylated
      aminoterminus (MANS peptide). Treatment of isolated human neutrophils with MANS
      significantly inhibited both their migration and beta2 integrin-dependent
      adhesion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), IL-8, or
      leukotriene (LT)B(4). The IC(50) for fMLF-induced migration and adhesion was 17.1
      microM and 12.5 microM, respectively. MANS significantly reduced the F-actin
      content in neutrophils 30 seconds after fMLF stimulation, although the peptide
      did not alter the ability of cells to polarize or spread. MANS did not alter fMLF
      induced increases in surface beta2 integrin expression. These results suggest
      that MARCKS, via its myristoylated aminoterminus, is a key regulator of
      neutrophil migration and adhesion.

PMID- 19574535
TI  - Gli2 influences proliferation in the developing lung through regulation of cyclin
      expression.
AB  - The sonic hedgehog (Shh) signaling pathway is crucial for normal lung
      development. In the lung, epithelial-produced Shh signals via mesenchymal Gli1-3
      transcription factors. Gli-null lung phenotypes suggest that Gli2 is the primary
      Gli transcription factor transducing Shh-regulated lung growth, although the
      mechanism has yet to be elucidated. To clarify the role of Gli2 during lung
      development, we overexpressed gli2 in the lung mesenchyme of mice, to investigate
      for changes in Shh signaling, and cellular proliferation. The ectopic
      overexpression of gli2 resulted in increased Shh pathway activation as evident by
      increased expression of shh, ptc1, ptc2, smo, hhip, and gli1. Interestingly, we
      also observed increased expression of gli3 transcripts. Using two different mouse
      models, gli3-null and gli3Delta699 (Gli3 constitutive repressor), it was found
      that Gli3 activity does not affect the levels of gli2 in the developing lung.
      Real-time PCR and immunoblotting revealed that there is increased expression of
      cyclins D1, D2, and E1 associated with increased gli2 levels. Furthermore, the
      increase and decrease of cyclins (associated with changes in gli2 levels)
      positively correlated with cellular proliferation, as assessed by phospho-histone
      H3 immunohistochemistry. To determine if Gli3 has an effect on cyclin expression
      in the developing lung, we measured the levels of cyclin D1, D2, and E1, in gli3
      null and gli3Delta699 mice and compared them to their wild-type counterparts.
      However, no change in the levels of cyclins D1, D2, or E1 due to altered Gli3 was
      observed. These findings suggest that Gli2 and not Gli3 is the primary mediator
      of Shh signaling influencing fetal lung growth through cyclin regulation.

PMID- 19574536
TI  - Differential sensitivity to administration format of measures of attitudes toward
      older adults.
AB  - PURPOSE: Reluctance to reveal sensitive or socially undesirable attitudes has
      posed a problem for measurement of personal attributes such as attitudes toward
      older people. These have long been documented to be negative and likely arise
      both from fears of one's own aging and the modern societal emphasis on youth. In
      order to increase our knowledge about the measurement of attitudes toward older
      people, we compared the administration of attitude measures toward older people
      by computer and conventional paper-and-pencil methods. DESIGN AND METHODS: We
      contrasted the responses of 60 university undergraduates (mean age 24.3 years, SD
      8.51; 68% female) to five traditional paper-and-pencil format attitude
      questionnaires toward older people with responses to the same questionnaires made
      using an Internet delivery and response mode. RESULTS: Results showed that more
      negative attitudes were revealed using the computer-based Internet response
      format for all scales. Only two scales did not show significant differences
      between formats. IMPLICATIONS: Future research on attitudes toward older people
      should be aware that results are dependent not only on the particular scale that
      is used but also on the format of administration, with more negative attitudes
      revealed with computer administration.

PMID- 19574537
TI  - Caregiver mental health and potentially harmful caregiving behavior: the central
      role of caregiver anger.
AB  - PURPOSE: Caregivers feeling stress and experiencing mental health problems can be
      at risk for engaging in abusive acts against elderly care recipients. Potentially
      harmful behavior (PHB) was used as a measure of caregivers' engagement in, or
      fear of engagement in, behavior that places dependent care recipients at risk of
      physical and/or psychological maltreatment and may be seen as an antecedent of,
      or a proxy for, identifiably abusive behavior. The study examined the ability of
      anger to mediate and moderate the relations of depression, resentment, and
      anxiety with PBH. DESIGN AND METHODS: Data are from the first wave of the second
      Family Relationships in Late Life study of caregivers of community-dwelling
      elderly care recipients with whom they coreside. Caregivers (N = 417) completed
      face-to-face interviews. RESULTS: Anger was found to mediate the relation between
      anxiety and PHB. Anger both mediates and moderates the relations of both
      depression and resentment with PHB in a dynamic way such that the mediating
      effect of anger increases substantially with increased scores on both depression
      and resentment. IMPLICATIONS: Identifying anger levels among caregivers who
      report symptoms of depression is warranted. Reducing depression in caregivers who
      report high levels of anger may result in reductions of PHB. Screening for
      resentment is warranted, as the relation between resentment and anger is similar
      to that between depression and anger.

PMID- 19574539
TI  - Quits and job changes among home care workers in Maine: the role of wages, hours,
      and benefits.
AB  - PURPOSE: Figuring out how to make home care jobs more attractive has become a top
      policy priority. This study investigates the impact of wages, hours, and benefits
      on the retention of home care workers. DESIGN AND METHODS: Using a 2-wave survey
      design and a sample of home care workers from Maine, the factors associated with
      turnover intentions, actual turnover, and job-to-job transitions are examined.
      The analysis uses actual data on hours, wages, and benefits at current and
      subsequent jobs and controls for perceived rewards and work conditions, personal
      characteristics, and local labor market conditions. RESULTS: Although the
      analysis finds that improved work conditions and non-pecuniary rewards of home
      based direct care work have significant negative effects on turnover intentions,
      compensation accounts for more actual job turnover. Higher wages, more hours, and
      travel cost reimbursement are found to be significantly associated with reduced
      turnover. Although wages and hours appear to have stronger effects, health
      benefits do appear to have some significance in predicting job-to-job
      transitions. IMPLICATION: Although improving compensation presents budgetary
      challenges to home care agencies, for this low-income workforce, the ability to
      earn higher wages and work more hours may be more of an imperative than improved
      work conditions.

PMID- 19574538
TI  - Measuring end-of-life care processes in nursing homes.
AB  - PURPOSE: The objectives of this study were to develop measures of end-of-life
      (EOL) care processes in nursing homes and to validate the instrument for
      measuring them. DESIGN AND METHODS: A survey of directors of nursing was
      conducted in 608 eligible nursing homes in New York State. Responses were
      obtained from 313 (51.5% response rate) facilities. Secondary data on structural
      characteristics of the nursing homes were obtained from the Online Survey
      Certification and Reporting System. Exploratory factor analyses and internal
      consistency reliability analyses were performed. Multivariate regression models
      with fixed and random effects were estimated. RESULTS: Four EOL process domains
      were identified-assessment, delivery, communication and coordination of care
      among providers, and communication with residents and families. The scales
      measuring these EOL process domains demonstrated acceptable to high internal
      consistency reliability and face, content, and construct validity. Facilities
      with more EOL quality assurance or monitoring mechanisms in place and greater
      emphasis on EOL staff education had better scores on EOL care processes of
      assessment, communication and coordination among providers, and care delivery.
      Facilities with better registered nurse and certified nurse aide staffing ratios
      and those with religious affiliation also scored higher on selected care process
      measures. IMPLICATIONS: This study offers a new validated tool for measuring EOL
      care processes in nursing homes. Our findings suggest wide variations in care
      processes across facilities, which in part may stem from lack of gold standards
      for EOL practice in nursing homes.

PMID- 19574540
TI  - Understanding patterns of service utilization among informal caregivers of
      community older adults.
AB  - PURPOSE: The article seeks to identify patterns of service utilization among
      informal caregivers of frail older adults. In particular, the study examined
      determinants that explain heterogeneous variations in caregivers' service use
      patterns. METHODS: Using a latent class analysis (LCA) on the 2004 National Long
      Term Care Survey and Informal Caregiver data (n = 1,908), this study classifies
      overall patterns of caregiver service utilization: financial information, support
      group, respite service, day care or senior center, personal or nursing care,
      housework, meal delivery, transportation, house modification, and assistive
      devices. With an emphasis on caregivers' service use patterns and social network
      derived from the Network Episode Model, the modified Andersen model guides
      determinants of these patterns. RESULTS: The LCA classified a hierarchical
      structure of service use patterns: multiple service users, selective in-home
      service users, and light service users. Caregivers' network compositions
      signified heterogeneity in service use patterns. Care recipient- and caregiver
      related needs contributed to distinguishing service use patterns. IMPLICATIONS:
      Differentiation of services may be important for meeting caregivers' needs and
      distributing program resources by identifying target populations for
      intervention. This typology process may tailor specific interventions to better
      support caregivers.

PMID- 19574541
TI  - Recruiting older adults into a physical activity promotion program: Active Living
      Every Day offered in a naturally occurring retirement community.
AB  - PURPOSE: This article explores recruitment strategies based on the
      transtheoretical model (TTM) with older adults living in a naturally occurring
      retirement community (NORC) to encourage enrollment in a physical activity
      promotion program, Active Living Every Day (ALED). Reasons for participation or
      nonparticipation are identified. DESIGN AND METHODS: Recruitment strategies were
      designed to move older adults through the TTM stages of change to enroll in ALED
      and were built on meetings and resources established by St. Louis NORC's
      supportive service program. NORC residents (25 ALED participants and 25
      nonparticipants) were interviewed about reasons for enrollment or nonenrollment.
      RESULTS: A significant difference was found between the two groups on their
      responses to a physical activity stage-of-change question, although no
      significant differences were found in their demographics, social resources, and
      mood/depression. ALED participants' motivation to enroll primarily came from TTM
      proactive recruitment methods (88%) and less (12%) from reactive methods. Themes
      for ALED participants' choices to enroll included motivation to exercise,
      physical activity ideas from peers, social engagement, and trust in sponsoring
      organizations' staff and programs. Analysis of interview data identified that
      scheduling and cost were primary reasons for nonenrollment in ALED. IMPLICATIONS:
      Using theoretically based recruitment methods for older adults and a neighborhood
      approach through organizations such as a NORC may result in greater numbers of
      older adults participating in health promotion programs.

PMID- 19574542
TI  - Older voters and the 2008 election.
AB  - PURPOSE: In the 2008 presidential election, a majority of older persons voted for
      John McCain, the loser. The purposes of this report are to help illuminate why
      older voters were the only age-group that gave a majority to McCain and to
      delineate some ongoing issues in the analysis of older persons' voting behavior.
      METHODS: Analysis was undertaken by mining raw data from the 2008 Edison-Mitofsky
      national Election Day exit poll, as well as compilations from that poll that were
      published by various media that finance it. RESULTS: Republican leanings of the
      Eisenhower birth cohort that is presently among those aged 65 years and older
      were a factor, whereas the immediately succeeding younger cohorts did not
      manifest the same partisan predilection. Positive self-identification with the 72
      year -old McCain by voters aged 65-74 years seems to have been another factor,
      although there was no indication of such age identification among those aged 60
      64 years and 75 years and older. Race may have been a factor, although all groups
      of White voters aged 30 years and older gave McCain a substantial majority,
      whereas the youngest cohort of Whites, aged 18-29 years, favored Obama.
      IMPLICATIONS: In the study of age-group voting behavior, ongoing attention is
      needed to cohort and period effects, as well as candidates' contrasting
      individual characteristics-in addition to possible effects of campaign issues.

PMID- 19574543
TI  - Food avoidance and food modification practices of older rural adults: association
      with oral health status and implications for service provision.
AB  - PURPOSE: Dietary variation is important for health maintenance and disease
      prevention among older adults. However, oral health deficits impair ability to
      bite and chew foods. This study examines the association between oral health and
      foods avoided or modified in a multiethnic rural population of older adults. It
      considers implications for nutrition and medical service provision to this
      population. DESIGN AND METHODS: In-home interviews and oral examinations were
      conducted with 635 adults in rural North Carolina counties with substantial
      African American and American Indian populations. Avoidance and modification data
      were obtained for foods representing different dental challenges and dietary
      contributions. Data were weighted to census data for ethnicity and sex. Bivariate
      analyses of oral health measures and foods avoided used chi-square and logistic
      regression tests. Multivariable analyses used proportional odds or nominal
      regression models. RESULTS: Whole fruits and raw vegetables were the most
      commonly avoided foods; substantial proportions of older adults also avoided
      meats, cooked vegetables, and other foods. Food avoidance was significantly
      associated with self-rated oral health, periodontal disease, bleeding gums, dry
      mouth, having dentures, and having fewer anterior and posterior occlusal
      contacts. Associations persisted when controlling for demographic and
      socioeconomic status indicators. From 24% to 68% of participants reported
      modifying specific fruits, vegetables, and meats. Modifying harder foods was
      related to location of teeth and periodontal disease and softer foods to oral
      pain and dry mouth. IMPLICATIONS: Food services for older adults should consider
      their oral health status. Policy changes are needed to provide oral health care
      in benefits for older adults.

PMID- 19574544
TI  - Nursing aides' attitudes to elder abuse in nursing homes: the effect of work
      stressors and burnout.
AB  - BACKGROUND: Nursing aides' attitudes condoning elder abuse are a possible risk
      factor for executing abusive behaviors against elder residents of long-term care
      facilities but have been studied infrequently. PURPOSE: The purpose of the study
      was to assess nursing aides' attitudes that condone abusive behaviors toward
      elderly people, as well as the relationship of these attitudes to demographic
      variables, work stressors (role conflict, role ambiguity, and work overload),
      burnout, and perceived control, based on the theory of planned behavior (Ajzen,
      1988, Attitudes, personality and behavior. Milton Keynes: Open University Press)
      DESIGN AND METHODS: Two hundred and eight nursing aides from 18 nursing homes in
      Israel completed demographic, work stressors, burnout, and perceived control
      questionnaires and a case vignette questionnaire to test attitudes condoning
      elder abuse. RESULTS: The mean score of the attitudes condoning abusive behaviors
      was relatively high at 3.24 (SD = 0.59) on a 1-4 scale. Condoning abusive
      behaviors were closely associated with higher levels of work stressors, burnout,
      and low income. Multiple regression analyses revealed that demographic variables,
      work stressors, burnout, and perceived control explained 12% of the variance of
      condoning abusive behaviors among the nursing aides. Of these, role ambiguity,
      role conflict, and burnout were significantly associated with attitudes condoning
      abusive behaviors. In addition, burnout partially mediated the relationship
      between work stressors and attitudes condoning elder abuse. CONCLUSIONS: As
      nursing aides' attitudes condoning elder abuse may influence their actual
      behaviors, training and supervision programs should be developed to reduce work
      stressors and burnout and to modify these attitudes.

PMID- 19574545
TI  - Subjective fatigue, mental effort, and attention deficits after severe traumatic
      brain injury.
AB  - OBJECTIVE: Although fatigue is one of the most frequent complaints of individuals
      with traumatic brain injury (TBI), its mechanisms remain poorly understood. The
      objective of this study was to assess the relationships between subjective mental
      fatigue, mental effort, attention deficits, and mood after severe TBI. METHODS:
      and participants. A total of 27 patients with subacute/chronic severe TBI were
      compared with matched controls. Patients first rated their baseline subjective
      fatigue on the Fatigue Severity Scale (FSS) and on the Visual Analog Scale for
      Fatigue (VAS-F). Mood was assessed with the Montgomery and Asberg Depression
      Rating Scale (MADRS). Then, they performed a long-duration selective attention
      task, separated in 2 parts. Fatigue on the VAS-F was assessed again between the 2
      parts and at the end of the attention task. Patients were also asked to rate on
      the VAS the level of subjective mental effort devoted to the task. RESULTS:
      Patients reported a higher baseline fatigue than controls. They performed
      significantly poorer on the selective attention task. Significant correlations
      were found in the group with TBI between attention performance, mental effort,
      and subjective fatigue. Depression did not significantly correlate with fatigue.
      DISCUSSION AND CONCLUSIONS: These findings suggest that patients with more severe
      attention deficits have to produce higher levels of mental effort to manage a
      complex task, which may increase subjective fatigue, in line with the coping
      hypothesis.

PMID- 19574546
TI  - Genetic mapping of Mom5, a novel modifier of Apc(Min)-induced intestinal
      tumorigenesis.
AB  - The initial purpose of this study was to assess the role of estrogen receptor
      beta (ERbeta) in intestinal tumorigenesis by examining the effects of an ERbeta
      knockout (ERbeta(-/-)) on Apc(Min) mice. In order to accomplish this goal on a
      uniform genetic background, we were required to backcross the ERbeta knockout
      from the 129P2 genetic background to the B6 genetic background for 10
      generations. Midway through this process, we performed a test cross in which mice
      from the N(5) backcross generation of the ERbeta knockout strain were
      intercrossed with Apc(Min/+) mice to obtain Apc(Min/+) ERbeta(+/+), Apc(Min/+)
      ERbeta(+/-) and Apc(Min/+) ERbeta(-/-) mice. Intestinal tumorigenesis in the
      N(5)F(2) mice was evaluated at 14 weeks of age. The analysis of the impact of
      ERbeta in the N(5) cross was complicated by segregating 129P2-derived alleles
      that affected tumor number and were unlinked to ERbeta. Genetic linkage analysis
      of this cross permitted the localization of a single genetic modifier of tumor
      number in Apc(Min/+) mice. This locus, Modifier of Min 5 (Mom5), maps to proximal
      mouse chromosome 5; the 129P2 allele of this locus is associated with a 50%
      reduction in mean intestinal tumor number. Through in silico analysis and
      confirmatory sequencing, we have identified the Rad50-interacting protein-1 gene
      as a strong candidate for Mom5.

PMID- 19574547
TI  - Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic
      cardiomyopathy through haploinsufficiency.
AB  - RATIONALE: Most sarcomere gene mutations that cause hypertrophic cardiomyopathy
      are missense alleles that encode dominant negative proteins. The potential
      exceptions are mutations in the MYBPC3 gene (encoding cardiac myosin-binding
      protein-C [MyBP-C]), which frequently encode truncated proteins. OBJECTIVE: We
      sought to determine whether there was evidence of haploinsufficiency in
      hypertrophic cardiomyopathy caused by MYBPC3 mutations by comparing left
      ventricular muscle from patients undergoing surgical myectomy with samples from
      donor hearts. METHODS AND RESULTS: MyBP-C protein and mRNA levels were
      quantitated using immunoblotting and RT-PCR. Nine of 37 myectomy samples had
      mutations in MYBPC3: 2 missense alleles (Glu258Lys, Arg502Trp) and 7 premature
      terminations. No specific truncated MyBP-C peptides were detected in whole muscle
      homogenates of hypertrophic cardiomyopathy tissue. However, the overall level of
      MyBP-C in myofibrils was significantly reduced (P<0.0005) in tissue containing
      either a truncation or missense MYBPC3 mutation: 0.76+/-0.03 compared with 1.00+/
      0.05 in donor and 1.01+/-0.06 in non-MYBPC3 mutant myectomies. CONCLUSIONS: The
      absence of any detectable truncated MyBP-C argues against its incorporation in
      the myofiber and any dominant negative effect. In contrast, the lowered relative
      level of full length protein in both truncation and missense MYBPC3 mutations
      argues strongly that haploinsufficiency is sufficient to cause the disease.

PMID- 19574548
TI  - Cardiomyocyte-specific loss of neurofibromin promotes cardiac hypertrophy and
      dysfunction.
AB  - RATIONALE: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder
      with a broad array of clinical manifestations, including benign and malignant
      tumors, and characteristic cutaneous findings. NF1 patients also have an
      increased incidence of cardiovascular diseases, including obstructive vascular
      disorders and hypertension. The disease gene, NF1, encodes neurofibromin, a
      ubiquitously expressed protein that acts, in part, as a Ras-GAP (GTP-ase
      activating protein), downregulating the activity of activated Ras protooncogenes.
      In animal models, endothelial and smooth muscle expression of the disease gene is
      critical for normal heart development and the prevention of vascular disease,
      respectively. OBJECTIVE: To determine the role of NF1 in the postnatal and adult
      heart. METHODS AND RESULTS: We generated mice with homozygous loss of the murine
      homolog Nf1 in myocardium (Nf1mKO) and evaluated their hearts for biochemical,
      structural, and functional changes. Nf1mKO mice have normal embryonic
      cardiovascular development but have marked cardiac hypertrophy, progressive
      cardiomyopathy, and fibrosis in the adult. Hyperactivation of Ras and downstream
      pathways are seen in the heart with the loss of Nf1, along with activation of a
      fetal gene program. CONCLUSIONS: This report describes a critical role of Nf1 in
      the regulation of cardiac growth and function. Activation of pathways known to be
      involved in cardiac hypertrophy and dysfunction are seen with the loss of
      myocardial neurofibromin.

PMID- 19574549
TI  - G protein-coupled receptor APJ and its ligand apelin act downstream of Cripto to
      specify embryonic stem cells toward the cardiac lineage through extracellular
      signal-regulated kinase/p70S6 kinase signaling pathway.
AB  - RATIONALE: Pluripotent stem cells represent a powerful model system to study the
      early steps of cardiac specification for which the molecular control is largely
      unknown. The EGF-CFC (epidermal growth factor-Cripto/FRL-1/Cryptic) Cripto
      protein is essential for cardiac myogenesis in embryonic stem cells (ESCs).
      OBJECTIVE: Here, we study the role of apelin and its G protein-coupled receptor,
      APJ, as downstream targets of Cripto both in vivo and in ESC differentiation.
      METHODS AND RESULTS: Gain-of-function experiments show that APJ suppresses
      neuronal differentiation and restores the cardiac program in Cripto(-/-) ESCs.
      Loss-of-function experiments point for a central role for APJ/apelin in the gene
      regulatory cascade promoting cardiac specification and differentiation in ESCs.
      Remarkably, we show for the first time that apelin promotes mammalian
      cardiomyogenesis via activation of mitogen-activated protein kinase/p70S6 through
      coupling to a Go/Gi protein. CONCLUSIONS: Together our data provide evidence for
      a previously unrecognized function of APJ/apelin in the Cripto signaling pathway
      governing mesoderm patterning and cardiac specification in mammals.

PMID- 19574550
TI  - Thrombin stimulates smooth muscle cell differentiation from peripheral blood
      mononuclear cells via protease-activated receptor-1, RhoA, and myocardin.
AB  - RATIONALE: Smooth muscle precursor cells have previously been reported to reside
      in bone marrow and in the circulation, but little is currently known regarding
      the proximate stimuli for smooth muscle cell differentiation of these putative
      progenitors. OBJECTIVE: Because local thrombin generation occurs as an initial
      response to vascular injury, we hypothesized that thrombin may influence the
      differentiation of circulating smooth muscle progenitor cells. METHODS AND
      RESULTS: Peripheral blood mononuclear cells were cultured on type I collagen
      using a protocol optimized to stimulate smooth muscle cell outgrowth. Thrombin
      stimulated upregulation of the transcription factor myocardin and smooth muscle
      myosin heavy chain, and both were inhibited by hirudin or the RhoA inhibitor
      Y27632. After 10 days of culture, smooth muscle outgrowth colonies formed, which
      stained positive for alpha-smooth muscle actin, smooth muscle myosin heavy chain,
      and calponin, in addition to having a contractile response to 100 nmol/L
      angiotensin II. Coincubation of peripheral blood mononuclear cells with thrombin,
      10 micromol/L protease-activated receptor-1, but not protease-activated receptor
      4 activating peptide significantly increased the number of smooth muscle
      outgrowth colonies formed. Thrombin-induced enhancement of smooth muscle
      outgrowth colony formation was inhibited by hirudin, Y27632, and an antibody
      against protease-activated receptor-1. CONCLUSIONS: These data illustrate a novel
      thrombin-induced pathway for smooth muscle differentiation from putative smooth
      muscle progenitors in peripheral blood.

PMID- 19574551
TI  - Functional characterization of a putative serine carboxypeptidase in vascular
      smooth muscle cells.
AB  - RATIONALE: We previously identified a novel serine carboxypeptidase, SCPEP1, that
      undergoes cleavage across all tissues where it is expressed. SCPEP1 bears the
      signature catalytic triad found in all serine carboxypeptidases, but its
      biological function is completely unknown. OBJECTIVE: To begin elucidating the
      functions of SCPEP1 in vitro and in the vessel wall after injury. METHODS AND
      RESULTS: Cultured smooth muscle cells were transduced with adenovirus carrying
      wild-type Scpep1, a short hairpin RNA to Scpep1, or variants of Scpep1 with
      mutations that disrupt the catalytic triad domain or SCPEP1 cleavage. Western
      blotting of key growth regulators or growth and migratory responses were assessed
      following SCPEP1 gain- or loss-of-function in smooth muscle cells. Vascular
      injury-induced remodeling and cell proliferation were evaluated in wild-type or
      newly created Scpep1 knockout mice. Overexpression of wild-type or cleavage
      defective SCPEP1, but not a catalytic triad mutant SCPEP1, promotes smooth muscle
      cell proliferation and migration in vitro. A short hairpin RNA to Scpep1 blunts
      endogenous growth, which is rescued on concurrent expression of Scpep1 carrying
      silent mutations that evade knockdown. SCPEP1 protein is highly expressed in the
      neointima of 2 models of vascular remodeling. Scpep1-null mice show decreases in
      medial and intimal cell proliferation as well as vessel remodeling following
      arterial injury. CONCLUSIONS: SCPEP1 promotes smooth muscle cell proliferation
      and migration in a catalytic triad-dependent, cleavage-independent manner. SCPEP1
      represents a new mediator of vascular remodeling and a potential therapeutic
      target for the treatment of vascular occlusive diseases.

PMID- 19574554
TI  - Long-term outcome after surgical treatment for space-occupying cerebellar
      infarction: experience in 56 patients.
AB  - BACKGROUND AND PURPOSE: Surgical management of space-occupying cerebellar
      infarction is still controversial. Data on long-term outcome are lacking. The
      objective of this study was (1) to evaluate outcome after at least 3 years
      poststroke in patients with space-occupying cerebellar infarction treated by
      ventriculostomy/extraventricular drainage (EVD) or suboccipital decompressive
      craniectomy (SDC), or both, and (2) to determine predicting factors for outcome.
      METHODS: In this retrospective single-center study 56 consecutive patients with
      acute space-occupying cerebellar infarction treated surgically between 1996 and
      2005 were included. Baseline data included clinical findings, Glasgow Coma Scale
      on admission and before surgery, NIHSS on admission, mass effects on
      neuroimaging, and surgical treatment strategies. Modified Rankin Scale, NIHSS,
      and Scale for the Assessment and Rating of Ataxia were used to assess outcome.
      RESULTS: 39.3% of patients had died, 51.8% had a mRS < or =3, 35.7% had a mRS <
      or =2, 28.6% had a mRS < or =1. There were no significant differences in survival
      between treatment groups. In multivariate analysis age and mRS score at discharge
      were the most evident independent predictors for outcome. CONCLUSIONS: So far
      this is the largest study on long-term outcome after space-occupying cerebellar
      infarction. The value of different treatment strategies and prognostic factors
      for patient selection remain unclear and should be evaluated in larger
      prospective case-series or registries. To investigate the issue of preventive SDC
      randomized trials are needed.

PMID- 19574553
TI  - Systematic characterization of the computed tomography angiography spot sign in
      primary intracerebral hemorrhage identifies patients at highest risk for hematoma
      expansion: the spot sign score.
AB  - BACKGROUND AND PURPOSE: The presence of active contrast extravasation (the spot
      sign) on computed tomography (CT) angiography has been recognized as a predictor
      of hematoma expansion in patients with intracerebral hemorrhage. We aim to
      systematically characterize the spot sign to identify features that are most
      predictive of hematoma expansion and construct a spot sign scoring system.
      METHODS: We retrospectively reviewed CT angiograms performed in all patients who
      presented to our emergency department over a 9-year period with primary
      intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours
      of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms
      and determined the presence and characteristics of spot signs according to strict
      radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes
      were determined by computer-assisted volumetric analysis. RESULTS: We identified
      spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs
      (8%). The presence of any spot sign increased the risk of significant hematoma
      expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined,
      the presence of > or =3 spot signs, a maximum axial dimension > or =5 mm, and
      maximum attenuation > or =180 Hounsfield units were independent predictors of
      significant hematoma expansion, and these were subsequently used to construct the
      spot sign score. In multivariate analysis, the spot sign score was the strongest
      predictor of significant hematoma expansion, independent of time from ictus to CT
      angiogram evaluation. CONCLUSIONS: The spot sign score predicts significant
      hematoma expansion in primary intracerebral hemorrhage. If validated in other
      data sets, it could be used to select patients for early hemostatic therapy.

PMID- 19574552
TI  - Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth
      muscle cells.
AB  - RATIONALE: NADPH oxidases (Noxes) regulate vascular physiology and contribute to
      the pathogenesis of vascular disease. In vascular smooth muscle cells (VSMCs),
      the interactions of individual Nox homologs with regulatory proteins are poorly
      defined. OBJECTIVE: The objective of this study was to identify novel NADPH
      oxidase regulatory proteins. METHODS AND RESULTS: Using a yeast 2-hybrid screen,
      we identified a novel p22phox binding partner, Poldip2, and demonstrated that it
      associates with p22phox, NADPH oxidase (Nox)1, and Nox4 and colocalizes with
      p22phox at sites of Nox4 localization. Poldip2 increases Nox4 enzymatic activity
      by 3-fold and positively regulates basal reactive oxygen species production in
      VSMCs (O2(.-): 86.3+/-15.6% increase; H2O2: 40.7+/-4.5% increase). Overexpression
      of Poldip2 activates Rho (180.2+/-24.8% increase), strengthens focal adhesions,
      and increases stress fiber formation. These phenotypic changes are blocked by
      dominant negative Rho. In contrast, depletion of either Poldip2 or Nox4 results
      in a loss of these structures, which is rescued by adding back active Rho. Cell
      migration, which requires dynamic cytoskeletal remodeling, is impaired by either
      excess (70.1+/-14.7% decrease) or insufficient Poldip2 (63.5+/-5.9% decrease).
      CONCLUSIONS: These results suggest that Poldip2 associates with p22phox to
      activate Nox4, leading to regulation of focal adhesion turnover and VSMC
      migration, thus linking reactive oxygen species production and cytoskeletal
      remodeling. Poldip2 may be a novel therapeutic target for vascular pathologies
      with a significant VSMC migratory component, such as restenosis and
      atherosclerosis.

PMID- 19574555
TI  - Long-term outcome after suboccipital decompressive craniectomy for malignant
      cerebellar infarction.
AB  - BACKGROUND AND PURPOSE: Suboccipital decompressive craniectomy (SDC) is a life
      saving intervention for patients with malignant cerebellar infarction. However,
      long-term outcome has not been systematically analyzed. METHODS: In this
      monocentric retrospective study we analyzed mortality, long-term functional
      outcome, and quality of life of all consecutive patients that were treated by SDC
      for malignant cerebellar infarction in our institution between 1995 and 2006.
      RESULTS: A total of 57 patients were identified. All of them were treated by
      bilateral SDC. An external ventricular drainage was inserted in 82%, necrotic
      tissue was evacuated in 56% of patients. There were no fatal procedural
      complications. Five patients were lost for follow-up. In the remaining 52
      patients, the mean follow-up interval was 4.7 years (1 to 11 years). Within the
      first 6 months after surgery 16 of 57 patients (28%) had died. At follow-up, 21
      of 52 patients (40%) had died and 4 patients (8%) lived with major disability
      (mRS 4 or 5). Twenty-one patients (40%) lived functionally independent (mRS 0 to
      2). The presence of additional brain stem infarction was associated with poor
      outcome (mRS > or =4; hazard ratio: 9.1; P=0.001). Quality of life in survivors
      was moderately lower than in healthy controls. CONCLUSIONS: SDC is a safe
      procedure in patients with malignant cerebellar infarction. Infarct- but not
      procedure-related early mortality is substantial. Long-term outcome in survivors
      is acceptable, particularly in the absence of brain stem infarction.

PMID- 19574556
TI  - Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent
      mechanism in human endothelial cells.
AB  - OBJECTIVE: We previously reported that interferons (IFNs) regulate transcription
      of HIF-1alpha in human endothelial cells (ECs), linking immunity and hypoxia.
      Prolyl hydroxylases (PHDs) regulate expression of HIF-1alpha in response to
      hypoxia. We examined whether IFNs affect PHD expression and whether PHDs regulate
      the EC response to IFNs. METHODS AND RESULTS: Human cell cultures were treated
      with various cytokines, and PHD expression was examined using qRT-PCR and
      immunoblotting. IFNgamma and, to a lesser extent, IFNalpha significantly induced
      PHD3, but not PHD1 or 2, mRNA, and protein expression selectively in ECs directly
      via a JAK/STAT1 pathway as demonstrated by pharmacological inhibition, siRNA
      knockdown, and chromatin immunoprecipitation. Inhibition of PHD activity with
      dimethyloxallyl glycine or desferroxamine reduced IFNg-dependent responses in
      these same cells. CONCLUSIONS: IFNgamma induces PHD3 through a JAK/STAT1
      dependent mechanism in human ECs. Induction is independent of HIF-1alpha and may
      contribute to expression of IFNgamma-dependent genes.

PMID- 19574557
TI  - Nox2-containing NADPH oxidase deficiency confers protection from hindlimb
      ischemia in conditions of increased oxidative stress.
AB  - OBJECTIVE: Because Nox2-containing NADPH oxidase is a major source of ROS in the
      vasculature, we investigated its potential role for the modulation of ischemia
      induced neovascularization in conditions of increased oxidative stress. METHODS
      AND RESULTS: To mimic a clinical situation of increased oxidative stress, mice
      were exposed to cigarette smoke before and after the surgical induction of
      hindlimb ischemia. Nox2 expression and oxidative stress in ischemic tissues were
      significantly increased in wild-type mice, but not in mice deficient for the Nox2
      containing NADPH oxidase (Nox2(-/-)). Nox2(-/-) mice demonstrated faster blood
      flow recovery, increased capillary density in ischemic muscles, and improved
      endothelial progenitor cell functional activities compared to Nox2(+/+) mice. In
      addition, Nox2 deficiency was associated with increased antioxidant and nitrite
      concentrations in plasma, together with a preserved expression of eNOS in
      ischemic tissues. In vitro, Nox2(-/-) endothelial cells exhibit resistance
      against superoxide induction and improved VEGF-dependent angiogenic activities
      compared to Nox2(+/+) endothelial cells. Importantly, the beneficial effects of
      Nox2 deficiency on neovascularization in vitro and in vivo were lost after
      treatment with the NO inhibitor L-NAME. CONCLUSIONS: Nox2-containing NADPH
      oxidase deficiency protects against ischemia in conditions of increased oxidative
      stress. The mechanism involves improved neovascularization through a reduction of
      ROS formation, preserved activation of the VEGF/NO angiogenic pathway, and
      improved functional activities of endothelial progenitor cells.

PMID- 19574558
TI  - Recombinant plasminogen activator inhibitor-1 inhibits intimal hyperplasia.
AB  - OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) overexpression is implicated
      in vascular disease. However, the effects of a primary increase in PAI-1
      expression on arterial remodeling are poorly defined. We tested the hypothesis
      that recombinant PAI-1 inhibits intimal hyperplasia after vascular injury.
      METHODS AND RESULTS: Rats underwent carotid artery injury and received
      intraperitoneal injections of saline or mutant forms of PAI-1 for 14 days,
      including an active stable mutant (PAI-1-14-1b), a mutant lacking anti-PA
      activity (PAI-1-R), or a mutant defective in vitronectin (VN) binding (PAI-1-K).
      All forms of PAI-1 significantly inhibited neointima formation, whereas elastase
      cleaved PAI-1, which lacks both anti-PA and VN-binding functions, did not.
      Similar effects were observed in a murine model. However, the antiproliferative
      effect of PAI-1-R was lost in Vn(-/-) mice, suggesting that PAI-1 can inhibit
      intimal hyperplasia in vivo by a VN-dependent pathway not involving direct
      inhibition of proteases. In vitro, recombinant PAI-1 inhibited wild-type vascular
      smooth muscle cell (VSMC) proliferation, promoted apoptosis, and inhibited
      migration. These effects were lost in VN-deficient VSMCs. CONCLUSIONS:
      Recombinant PAI-1 inhibits intimal hyperplasia by inhibiting proteases and
      binding VN. VN is a key determinant of the antiproliferative effect of PAI-1
      overexpression. PAI-1-R has therapeutic potential to inhibit vascular restenosis
      without promoting thrombosis.

PMID- 19574559
TI  - Analysis of in situ and ex vivo vascular endothelial growth factor receptor
      expression during experimental aortic aneurysm progression.
AB  - OBJECTIVE: Mural inflammation and neovascularization are characteristic
      pathological features of abdominal aortic aneurysm (AAA) disease. Vascular
      endothelial growth factor receptor (VEGFR) expression may also mediate AAA growth
      and rupture. We examined VEGFR expression as a function of AAA disease
      progression in the Apolipoprotein E-deficient (Apo E(-/-)) murine AAA model.
      METHODS AND RESULTS: Apo E(-/-) mice maintained on a high-fat diet underwent
      continuous infusion with angiotensin II at 1000 ng/kg/min (Ang II) or vehicle
      (Control) via subcutaneous osmotic pump. Serial transabdominal ultrasound
      measurements of abdominal aortic diameter were recorded (n=16 mice, 3 to 4 time
      points per mouse) for up to 28 days. Near-infrared receptor fluorescent (NIRF)
      imaging was performed on Ang II mice (n=9) and Controls (n=5) with scVEGF/Cy, a
      single-chain VEGF homo-dimer labeled with Cy 5.5 fluorescent tracer (7 to 18
      microg/mouse IV). NIRF with inactivated single chain VEGF/Cy tracer (scVEGF/In,
      18 microg/mouse IV) was performed on 2 additional Ang II mice to control for
      nonreceptor-mediated tracer binding and uptake. After image acquisition and
      sacrifice, aortae were harvested for analysis. An additional AAA mouse cohort
      received either an oral angiogenesis inhibitor or suitable negative or positive
      controls to clarify the significance of angiogenesis in experimental aneurysm
      progression. Aneurysms developed in the suprarenal aortic segment of all Ang II
      mice. Significantly greater fluorescent signal was obtained from aneurysmal aorta
      as compared to remote, uninvolved aortic segments in Ang II scVEGF/Cy mice or AAA
      in scVEGF/In mice or suprarenal aortic segments in Control mice. Signal intensity
      increased in a diameter-dependent fashion in aneurysmal segments. Immunostaining
      confirmed mural VEGFR-2 expression in medial smooth muscle cells. Treatment with
      an angiogenesis inhibitor attenuated AAA formation while decreasing mural
      macrophage infiltration and CD-31(+) cell density. CONCLUSIONS: Mural VEGFR
      expression, as determined by scVEGF/Cy fluorescent imaging and VEGFR-2
      immunostaining, increases in experimental AAAs in a diameter-dependent fashion.
      Angiogenesis inhibition limits AAA progression. Clinical VEGFR expression imaging
      strategies, if feasible, may improve real-time monitoring of AAA disease
      progression and response to suppressive strategies.

PMID- 19574560
TI  - Junctional adhesion molecule-C mediates leukocyte infiltration in response to
      ischemia reperfusion injury.
AB  - OBJECTIVE: Junctional adhesion molecule-C (JAM-C) is an adhesion molecule that
      has multiple roles in inflammation and vascular biology, but many aspects of its
      functions under pathological conditions are unknown. Here we investigated the
      role of JAM-C in leukocyte migration in response to ischemia reperfusion (I/R)
      injury. METHODS AND RESULTS: Pretreatment of mice with soluble JAM-C (sJAM-C),
      used as a pharmacological blocker of JAM-C-mediated reactions, significantly
      suppressed leukocyte migration in models of kidney and cremaster muscle I/R
      injury (39 and 51% inhibition, respectively). Furthermore, in the cremaster
      muscle model (studied by intravital microscopy), both leukocyte adhesion and
      transmigration were suppressed in JAM-C-deficient mice (JAM-C(-/-)) and enhanced
      in mice overexpressing JAM-C in their endothelial cells (ECs). Analysis of JAM-C
      subcellular expression by immunoelectron microscopy indicated that in I/R-injured
      tissues, EC JAM-C was redistributed from cytoplasmic vesicles and EC junctional
      sites to nonjunctional plasma membranes, a response that may account for the role
      of JAM-C in both leukocyte adhesion and transmigration under conditions of I/R
      injury. CONCLUSIONS: The findings demonstrate a role for EC JAM-C in mediating
      leukocyte adhesion and transmigration in response to I/R injury and indicate the
      existence of a novel regulatory mechanism for redistribution and hence function
      of EC JAM-C in vivo.

PMID- 19574561
TI  - Fish oil promotes macrophage reverse cholesterol transport in mice.
AB  - OBJECTIVE: Fish oil (FO), and specifically omega 3 fatty acids, has favorable
      effects on cardiovascular outcomes. The aim of this study was to investigate the
      effects of FO on the process of macrophage reverse cholesterol transport (RCT) in
      an in vivo mouse model. METHODS AND RESULTS: C57BL/6J mice were fed a FO diet,
      whereas control mice were fed diets containing alternative sources of fats,
      soybean oil (SO), and coconut oil (CO) for 4 weeks. Macrophage RCT was assessed
      by injecting [(3)H]cholesterol-labeled J774 macrophages intraperitoneally into
      mice. After 48 hours, tissues were harvested and feces were collected. An
      increase in the excretion of macrophage-derived [(3)H]-tracer recovered in fecal
      neutral sterols for FO-fed mice was observed (273% versus SO and 182% versus CO).
      FO also decreased [(3)H]-tracer in hepatic cholesteryl ester compared to SO and
      CO by 76% and 56%, respectively. To specifically determine the effect of FO on
      the fate of HDL-derived cholesterol, mice fed FO or SO diets were injected with
      HDL labeled with [(3)H]cholesteryl oleate, and the disappearance of [(3)H]-tracer
      from blood and its excretion in feces was measured. There was no significant
      difference in the fractional catabolic rate of [(3)H]cholesteryl oleate-HDL
      between the 2 groups. However, there was a 242% increase in the excretion of HDL
      derived [(3)H]-tracer recovered in fecal neutral sterols in FO-fed mice,
      concordant with significantly increased expression of hepatic Abcg5 and Abcg8
      mRNA. CONCLUSIONS: As measured by this tracer-based assay, FO promoted reverse
      cholesterol transport, primarily by enhancement of the hepatic excretion of
      macrophage-derived and HDL-derived cholesterol.

PMID- 19574563
TI  - Comparison of placental traits and their relation to litter size and parity
      weight in sheep.
AB  - The relationships between genotype and placental traits, parity and litter weight
      (LW), and factors affecting these characteristics were investigated in this
      study. In total, 112 ewes (Romanov crossbred and local breeds) were utilized. One
      way ANOVA was used for statistical comparison, and a Pearson correlation was used
      to determine the relationships between the variables. Significant differences in
      parity weight within genotype and breed have been determined. A negative
      correlation was revealed between placental weight (PW) and placental efficiency
      (r = -0.743, P < 0.01; and r = -0.732, P < 0.01). There was no relationship
      between litter sex and placental traits. Birth type had a significant effect on
      PW (P < 0.05), and significant differences within sex-birth type interactions
      occurred (P < 0.05). The results of the present study have shown a positive
      correlation between cotyledon density and placental efficiency among all
      genotypes and breeds that were used in the study. In conclusion, it has been
      determined that placental traits were affected by LW and Romanov crossbreed ewes
      had greater PW than local breeds. Further studies are required to investigate the
      relationship between parity and placental traits in sheep.

PMID- 19574562
TI  - Effects of short-term heat stress on endophytic ergot alkaloid-induced
      alterations in rat hepatic gene expression.
AB  - Exposure to ergot alkaloids in endophyte-infected fescue (E+) is associated with
      impaired animal productivity, especially during heat stress, which is commonly
      referred to as fescue toxicosis. To elucidate the pathogenesis of this condition,
      the effects of short-term heat stress (HS) on hepatic gene expression in rats
      exposed to endophytic ergot alkaloids were evaluated. Rats implanted with
      telemetric transmitters to continuously measure core temperature were fed an E+
      diet and maintained under thermoneutral (TN) conditions (21 degrees C) for 5 d,
      followed by TN or 31 degrees C (HS) conditions for 3 d. Feed intake (FI) and BW
      were monitored daily. The E+ and HS-induced alterations in hepatic genes were
      evaluated using DNA microarrays and PCR analyses. Hepatic antioxidant enzyme
      activities, as well as the incidence of apoptosis, were determined. As expected,
      intake of E+ reduced FI and BW from pretreatment levels under TN conditions, with
      greater reductions during short-term HS. Genes involved in gluconeogenesis and
      apoptosis were upregulated, whereas genes associated with oxidative
      phosphorylation, xenobiotic metabolism, antioxidative mechanisms, immune
      function, cellular proliferation, and chaperone activity were all downregulated
      with short-term HS. Hepatocytic apoptosis was increased and antioxidant enzyme
      activity decreased in the livers of rats exposed to HS. The hypothesized,
      exacerbating effects of HS on the direct, endophytic toxin-related and indirect,
      reduced caloric intake-associated alterations in hepatic gene expression were
      clearly demonstrated in rats and may help to elucidate the pathogenesis of fescue
      toxicosis in various animal species.

PMID- 19574564
TI  - A snapshot of management practices and nutritional recommendations used by
      feedlot nutritionists in Brazil.
AB  - Feedlot consulting nutritionists were invited to participate in a survey of
      feedlot nutritional and management practices in Brazil. Thirty-one nutritionists
      completed the survey on a Web site that was designed for collection of survey
      data. The survey consisted of 94 questions that included general information (n =
      10); commodity information (n = 12); and questions about the use of coproducts (n
      = 5), roughage source and levels (n = 5), finishing diet adaptation methods (n =
      7), supplements and micronutrients (n = 8), feed mixers (n = 6), feeding
      management (n = 3), cattle management and type of cattle fed (n = 16),
      formulation practices (n = 17), information resources used for nutritional
      recommendations (n = 2), and 2 additional questions. One final question addressed
      the primary challenges associated with applying nutritional recommendations in
      practice. The number of animals serviced yearly by each nutritionist averaged
      121,682 (minimum = 2,000; maximum = 1,500,000; mode = 120,000; total =
      3,163,750). Twenty-two respondents (71%) worked with feedlots that feed less than
      5,000 animals/yr. Labor, along with availability and precision of equipment,
      seemed to be the main challenges for the nutritionists surveyed. Most of the
      nutritionists surveyed used TDN as the primary energy unit for formulation. More
      than 50% of the clients serviced by the 31 nutritionists did not manage feed
      bunks to control the quantity of feed offered per pen, and 36.6% fed cattle more
      than 4 times daily. The NRC (1996) and Journal of Animal Science were the most
      used sources of information by these nutritionists. Overall, general practices
      and nutritional recommendations provided by the 31 nutritionists surveyed were
      fairly consistent. Present data should aid in development of new research, future
      National Research Council models, and recommendations for Brazilian feeding
      systems in which Bos indicus cattle predominate.

PMID- 19574565
TI  - Low-level fructan supplementation of dogs enhances nutrient digestion and
      modifies stool metabolite concentrations, but does not alter fecal microbiota
      populations.
AB  - Five ileal-cannulated adult dogs were utilized in a 5 x 5 Latin square design to
      determine the effects of fructan type and concentration on nutrient
      digestibility, stool metabolite concentrations, and fecal microbiota. Five diets
      were evaluated that contained cellulose alone or with inulin or short-chain
      fructooligosaccharides (scFOS) each at 0.2 or 0.4% of the diet. Dogs were fed 175
      g of their assigned diet twice daily. Chromic oxide served as a digestibility
      marker. Nutrient digestibility; ileal and fecal pH and ammonia concentrations;
      ileal IgA concentrations; and fecal short- and branched-chain fatty acid
      concentrations, microbiota, and concentrations of phenol, indole, and biogenic
      amines were measured. No differences were observed in ileal pH or ammonia or
      fecal concentrations of indole or valerate. Ileal DM, OM, and CP digestibility
      coefficients; total tract DM and OM digestibility coefficients; and fecal
      concentrations of phenylethylamine increased linearly (P < 0.05), and fecal
      concentrations of phenol decreased linearly (P < 0.05) with inulin
      supplementation. Fecal concentrations of acetate, propionate, and total short
      chain fatty acids decreased quadratically (P < 0.05) with inulin supplementation.
      Ileal DM, OM, and CP digestibility coefficients increased linearly (P < 0.05),
      and fecal phenol concentration decreased linearly (P < 0.05) with scFOS
      supplementation. Total tract DM and OM digestibility coefficients as well as
      fecal butyrate and isobutyrate concentrations increased quadratically (P < 0.05)
      with scFOS supplementation. Although a greater level of inclusion is needed to
      modify gut microbiota populations, low-level inclusion of inulin or scFOS is
      effective in modifying key nutritional outcomes in the dog.

PMID- 19574566
TI  - Effect of supplementing zinc oxide and biotin with or without carbadox on nursery
      pig performance.
AB  - A 28-d nursery experiment was conducted to evaluate the effects of supplementing
      zinc oxide and biotin with or without a feed-grade antimicrobial agent (carbadox)
      on nursery pig performance, and plasma and fecal Zn concentrations. One hundred
      ninety-two crossbred pigs (initial BW = 5.94 +/- 0.03 kg; age = 17 +/- 2 d) were
      weaned and allotted to 1 of 8 dietary treatments based on BW, sex, and ancestry
      in a randomized complete block design (3 pigs/pen and 8 replications). Dietary
      treatments consisted of supplementation of ZnO at 0 or 3,000 mg/kg, d-biotin at 0
      or 440 microg/kg, and carbadox at 0 or 55 mg/kg of diets in a 2 x 2 x 2 factorial
      arrangement of treatments. Phase 1 (d 0 to 14) and phase 2 (d 14 to 28) nursery
      diets were fed in meal form. Fecal samples were collected weekly, and blood
      samples were collected at d 0, 14, and 28 to determine fecal and plasma Zn
      concentrations, respectively. The basal diet contained 165 mg/kg of Zn as ZnSO(4)
      and 220 microg/kg biotin as d-biotin. Pigs supplemented with 440 microg/kg of d
      biotin, independent of antibiotic and ZnO additions, had greater overall ADG (P =
      0.02) than pigs fed no supplemental d-biotin postweaning. Overall ADG, ADFI, and
      G:F were not affected when pigs were supplemented with 3,000 mg/kg of Zn as ZnO
      or 55 mg/kg of carbadox. When pigs were fed 55 mg/kg of carbadox without
      supplemental biotin, plasma Zn concentration was less, whereas when biotin and
      carbadox were supplemented to nursery pig diets, plasma Zn concentrations did not
      decrease as with feeding carbadox alone (biotin x carbadox, P < 0.001). During wk
      2, pigs fed 3,000 mg/kg of Zn as ZnO and 440 microg/kg of d-biotin had greater
      fecal Zn concentrations than pigs fed diets with only 3,000 mg/kg of Zn as ZnO
      (Zn x biotin, P = 0.04). In addition, pigs supplemented with 3,000 mg/kg of Zn as
      ZnO in combination with carbadox and d-biotin had greater fecal Zn concentrations
      compared with pigs fed diets containing no additional Zn during wk 2 (Zn x biotin
      x carbadox, P = 0.04). Fecal Zn concentrations increased over time (P < 0.001),
      and pigs fed supplemental ZnO had greater (P < 0.001) fecal Zn concentrations.
      These results indicate that feeding nursery pigs 440 microg/kg of d-biotin
      improved ADG, independent of zinc and carbadox supplementation, as well as
      increasing Zn excretion.

PMID- 19574567
TI  - Effect of the degree and duration of early dietary amino acid restrictions on
      subsequent and overall pig performance and physical and sensory characteristics
      of pork.
AB  - The objective of this study was to investigate the effect of the degree and
      duration of early dietary AA restrictions on subsequent and overall pig
      performance and physical and sensory characteristics of pork. For the grower (G)
      and finisher-1 (F1) phases, 3 corn-soybean meal diets were formulated to contain
      100, 80, or 60% of the 1998 NRC total Lys recommendations (100G, 80G, or 60G, and
      100F1, 80F1, or 60F1, for the G and F1 phases, respectively). For the finisher-2
      (F2) phase, a common corn-soybean meal diet was formulated to satisfy the 1998
      NRC total Lys recommendation. Thirty gilts and 30 castrated males (2 gilts or 2
      castrated males/pen) were randomly assigned to 5 dietary treatments (100G-100F1,
      80G-100F1, 80G-80F1, 60G-100F1, and 60G-60F1) when BW was 22.7 +/- 0.3 kg. Pigs
      were switched to F1 and F2 diets at 50.7 +/- 0.4 and 79.9 +/- 0.5 kg of BW,
      respectively. Pigs had ad libitum access to feed and water. All pigs were
      slaughtered at 110.7 +/- 0.5 kg of BW, and LM samples were collected. Pigs fed
      the 60G diet had less (P < or = 0.05) ADG during the G phase and greater (P < or
      = 0.05) ultrasound backfat (UBF) at the end of the G phase than those fed the
      100G diet. The ADG decreased linearly (R(2) = 0.70; P < 0.001) as the degree of
      AA restrictions became more severe. Although serum total protein (TP) and albumin
      concentrations in pigs fed the 60G-100F1 diets were less (P < or = 0.05) than
      those fed the 100G-100F1 diets at the end of the G phase, TP concentration was
      similar between the 2 groups at the end of the F1 phase. Likewise, ADG during the
      F1 phase and UBF at the end of the F1 phase in pigs fed the 60G-100F1 diets were
      similar to those fed the 100G-100F1 diets. Feeding the 80G diet resulted in
      numerically decreased ADG during the G phase, but there was no difference in ADG
      during the F1 and F2 phases or UBF at the end of F1 and F2 phases between pigs
      fed the 80G and 100G diets. Overall, pigs fed the 80G-80F1 diets had similar ADG,
      but less (P < or = 0.05) fat-free lean gain (LG) than those fed the 100G-100F1
      diets. These pigs also had less (P < or = 0.05) serum TP and albumin
      concentrations than pigs fed the 100G-100F1 diets throughout the study. Pigs fed
      the 60G-60F1 diets had less (P < or = 0.05) overall ADG and G:F and less (P < or
      = 0.05) LM area and LG than those fed the 100G-100F1 diets. However, they had a
      greater (P < or = 0.05) subjective marbling score than those fed the 100G-100F1
      diets. The results indicated that pigs fed the 80G-80F1 diets may have exhibited
      compensatory growth in BW gain, but not in terms of lean accretion. Growth
      performance and carcass traits of pigs fed the 60G-60F1 diets were reduced,
      indicating that the restriction may have been too severe or too long or both.
      Early dietary AA restrictions had no clear effect on physical and sensory
      characteristics of pork.

PMID- 19574568
TI  - Technical note: correction of net portal absorption of nitrogen compounds for
      differences in methods: first step of a meta-analysis.
AB  - The objective of this study was to evaluate the usefulness of correcting net
      portal absorption (NPA) of urea-N, ammonia, and AA-N for differences in methods
      before their inclusion into a meta-analysis. It was hypothesized that the
      difference, or portal-drained viscera (PDV) balance, between N inputs (apparently
      digested N plus urea-N) and outputs (ammonia plus AA-N) was 0 in the absence of
      measurement errors and based on the assumption that other sources of N inputs and
      outputs were relatively small and balanced each other. A database was built from
      44 publications that reported data from 129 treatments (sheep, n = 71; beef
      cattle, n = 32; and dairy cows, n = 26). When necessary, NPA of urea-N (n = 38)
      and ammonia (n = 35) results were recalculated on a whole-blood basis, whereas
      NPA of AA-N (n = 87) was recalculated for all the N from AA transferred across
      the PDV rather than only the N from the alpha-amino group. Before corrections,
      PDV balance averaged 22.9% of N ingested (SD 29.0) for all treatments; after
      corrections, PDV balance significantly decreased to 10.2% of N ingested (SD
      34.7). No difference in PDV balance was observed among species before or after
      corrections. Correcting NPA of urea-N, ammonia, and AA-N increased the accuracy
      without improving precision. Therefore, from a biological perspective,
      recalculating reported data seems appropriate to reduce bias due to differences
      in methods because this approach reduces the excess in N inputs relative to N
      outputs.

PMID- 19574569
TI  - Effects of increasing field pea (Pisum sativum) level in high-concentrate diets
      on growth performance and carcass traits in finishing steers and heifers.
AB  - Three experiments were conducted to determine the effect of increasing field pea
      level in high-concentrate finishing cattle diets on ADG, DMI, G:F, and carcass
      traits, and to estimate the NE of field pea. In Exp. 1, 118 yearling heifers
      (417.9 +/- 2.4 kg initial BW) were blocked by initial BW and assigned randomly to
      1 of 4 treatments (0, 10, 20, or 30% dry-rolled field pea, DM basis; 4
      pens/treatment). In Exp. 2, 143 beef steers (433 +/- 19 kg initial BW) were
      blocked by BW and assigned randomly to 1 of 4 treatments (0, 10, 20, or 30% dry
      rolled field pea, DM basis; 6 pens/treatment). In Exp. 3, 80 beef steers (372.4
      +/- 0.4 kg initial BW) were assigned randomly to 1 of 4 treatments (0, 18, 27, or
      36% cracked field pea, DM basis; 4 pens/treatment). Field pea replaced a portion
      of the grain (dry-rolled and high moisture corn, dry-rolled corn, and barley and
      barley sprouts; Exp. 1, 2, and 3, respectively) and protein supplement. In Exp.
      1, field pea inclusion decreased DMI linearly (P = 0.03), whereas ADG and G:F
      were not affected by treatment (P > or = 0.17); however, dietary NE(g) increased
      quadratically with increasing field pea level (P = 0.04). Fat thickness responded
      quadratically (P = 0.008) where heifers fed 20% field pea had greatest fat
      thickness and 30% field pea inclusion the least. Marbling tended (P < or = 0.09)
      to respond quadratically as field pea increased. No differences (P > or = 0.17)
      were observed for HCW, LM area, or KPH. In Exp. 2, DMI, ADG, G:F, dietary NE(g),
      HCW, marbling, LM area, 12th-rib fat, and USDA yield grade (YG) were unaffected
      by dietary field pea inclusion (P > or = 0.12). In Exp. 3, marbling score
      increased linearly (P = 0.05), fat thickness increased quadratically (P = 0.01),
      and YG tended to increase (P = 0.07) quadratically as field pea increased. Field
      pea inclusion did not affect (P > or = 0.38) DMI, ADG, G:F, dietary NE(g), HCW,
      or LM area. These results indicate that field pea can be included successfully
      into rations at levels up to 36% of DM without negatively affecting growth
      performance and most carcass characteristics of finishing beef cattle; however,
      effects on marbling score were variable. These data also indicate the energy
      content of field peas is similar to cereal grains, such as corn and barley, when
      included in high-concentrate finishing diets.

PMID- 19574570
TI  - Dietary regulation of ruminal bovine UT-B urea transporter expression and
      localization.
AB  - Facilitative UT-B urea transporters have been located in the gastrointestinal
      tract of numerous mammalian species. We have previously identified UT-B urea
      transporters within the epithelial layers of the bovine (b) rumen. The aim of
      this study was to test the hypothesis that ruminal bUT-B urea transporters are
      regulated by dietary intake. Six Limousine-cross steers (initial BW = 690 +/- 51
      kg) were separated into 2 groups fed a basic silage-based diet (RS) or a
      concentrate-based diet (RC) for 37 d and compared for ruminal morphology,
      content, and bUT-B expression. Analysis by reverse transcription-PCR showed that
      ruminal bUT-B2 mRNA expression was greater in RC-fed than RS-fed animals.
      Utilizing an anti-bUT-B antibody, we also detected a significant increase in bUT
      B2 protein expression in RC-fed rumen (P < 0.05, n = 3). In agreement with these
      findings, immunolocalization studies of RC-fed ruminal tissue showed strong bUT-B
      signals throughout all epithelial layers, in contrast to weaker staining in RS
      fed rumen that was more localized to the stratum basale. This study therefore
      confirmed that ruminal bUT-B urea transporter expression and localization were
      indeed altered by changes in dietary intake. We conclude that UT-B transporters
      play a significant role in the dietary regulation of bovine nitrogen balance.

PMID- 19574571
TI  - Predicted limits for evaporative cooling in heat stress relief of cattle in warm
      conditions.
AB  - Evaporative cooling of ambient air (EC) is a main path for heat stress relief in
      cattle kept in the shade of semi-confining structures. Evaporative cooling is
      particularly efficient in hot dry climates. We examined the potential of EC for
      heat stress relief in cattle in moderately warm and humid climates. The
      feasibility was examined by the reduction in ambient temperature (T(ac)) produced
      by EC as a function of ambient temperature (T(a)) and humidity (RH(a)). A data
      set (n = 139) of temperature and relative humidity (RH) produced by EC over a
      range of air temperature (25 to 50 degrees C) and humidity (10 to 70% RH) was
      analyzed by polynomial second order regressions. The analyses produced equations
      for the relations between ambient air temperature and ambient humidity and
      between respective conditions in air cooled by EC (T(c), RH(c)). Linear
      regressions were computed for a narrower temperature range (30 to 40 degrees C).
      In all equations, R(2) were >0.94 and regression terms were statistically
      significant. The T(ac) obtained by EC diminished by 0.3 degrees C per degrees C
      rise in T(a), indicating a reduced efficiency of EC with rising T(a). The T(ac)
      obtained by EC also was markedly reduced by rising ambient humidity and increased
      by RH(c). An attempt to sustain T(ac) at greater RH(a) by allowing a rise in
      RH(c) would only restore 2/3 of the reduction in T(ac) because the coefficient
      for the RH(a) effect on T(ac) is 1.5 larger than that of RH(c). The T(ac)
      attained by EC partially depends on the humidity in the cooled environment.
      Elevated RH(c) may impede animal skin and respiratory evaporative heat loss and
      lead to moisture accumulation in bedding. If the upper desired limit for RH(c) is
      70%, at RH(a) smaller than 45% (typical for hot-dry environments) the T(ac) is
      larger than 7.5 degrees C, at RH(a) greater than 55% T(ac) is reduced to less
      than 5 degrees C, and at RH(a) of 57.5 to 60% T(ac) is about 2.5 degrees C.
      Coupling EC with forced air movement when T(ac) is small may partially assist in
      alleviation of heat stress by enhancing the smaller convective heat loss at
      ambient temperatures above 30 degrees C. These indicate a limited role for EC in
      relief of heat stress in moderately warm and humid conditions when RH(a) is
      greater than 50 to 55%. Forced evaporation of water from the surface of the
      animal by sequential hair coat wetting coupled with forced air movement is an
      alternative little affected by ambient humidity.

PMID- 19574572
TI  - Comparison of bloat potential between a variety of soft-red versus a variety of
      hard-red winter wheat forage.
AB  - Some aspects of wheat pasture bloat have been researched extensively, but few
      studies have evaluated the effect of wheat type or variety on bloat. Eight
      Gelbvieh x Angus ruminally cannulated heifers (515 +/- 49 kg of BW) and 48 Angus
      heifers (238 +/- 12 kg of BW) grazed 1-ha pastures of hard-red or soft-red winter
      wheat (Triticum aestivum L.) to evaluate the effect of wheat variety on bloat
      potential. In Exp. 1, cattle grazed from November 11 to 22 and from November 26
      to December 7, 2006, in a crossover design. In Exp. 2, cattle were shrunk for 20
      h and then grazed from December 19 to 20, 2006, and from January 19 to 20, 2007.
      In both experiments, bloat was scored at 1000 and 1600 h daily. Rumen samples
      were collected at 0600, 1200, and 1800 h during each of the last 2 d of each
      period in Exp. 1 and during both days of each period of Exp. 2. Rumen samples
      were evaluated for pH, foam production and strength, and viscosity. In Exp. 1,
      cannulated heifers grazing soft-red had a greater (P < 0.01) percentage of
      observed bloat (21.9 vs. 5.6%) than those grazing hard-red winter wheat, but
      bloat incidence was low (2.1%) for the stocker cattle, with no difference between
      hard-red and soft-red winter wheat (P = 0.52). Viscosity of the rumen fluid was
      affected (P = 0.03) by the wheat variety x time interaction, with soft-red at
      1200 and 1800 h being more viscous than soft-red at 0600 h and hard-red at all
      times. Foam strength, as determined by bubbling CO(2) gas through rumen fluid,
      had a wheat variety x time interaction (P = 0.02) with both wheat varieties
      similar at 0600 h but soft-red having greater foam strength at 1200 and 1800 h.
      In Exp. 2, no bloat was observed, and no differences between wheat varieties were
      observed for any of the rumen foam measures. Therefore, for these 2 varieties,
      the soft-red winter wheat had a greater bloat potential than the hard-red winter
      wheat based on results from the cannulated heifers, but no differences were
      observed in the frequency of bloat in stocker cattle. In this study, shrinking of
      cattle before grazing wheat pasture did not induce bloat.

PMID- 19574573
TI  - Genetic validation of postmixing skin injuries in pigs as an indicator of
      aggressiveness and the relationship with injuries under more stable social
      conditions.
AB  - The objective of the study was to estimate genetic correlations between skin
      lesions and aggressive behavior postmixing and under more stable social
      conditions as a potential means of selecting against pig aggressiveness.
      Postmixing aggression in commercial pig production is common, compromises welfare
      and profitability, and cannot be significantly reduced by low-cost changes to the
      environment. A genetic component to individual aggressiveness has been described
      in pigs and other species. Selective breeding against aggressiveness ought to be
      possible if an easily measured indicator trait can be shown to be genetically
      associated with aggressive behavior. Aggressive behavior was recorded
      continuously for 24 h after mixing, and a count of skin lesions (lesion count,
      LC) was recorded at 24 h and 3 wk postmixing on 1,663 pigs. Two behavioral traits
      were found to have a moderate to high heritability similar to that of growth
      traits; duration of involvement in reciprocal fighting (0.43 +/- 0.04) and
      delivery of nonreciprocal aggression (NRA; 0.31 +/- 0.04), whereas receipt of NRA
      had a lower heritability (0.08 +/- 0.03). Genetic correlations (r(g)) suggested
      that lesions to the anterior region of the body 24 h after mixing were associated
      with reciprocal fighting (r(g) = 0.67 +/- 0.04), receipt of NRA (r(g) = 0.70 +/-
      0.11), and to a lesser extent, delivery of NRA (r(g) = 0.31 +/- 0.06). Lesions to
      the center and rear were primarily genetically associated with receipt of NRA
      (r(g) = 0.80 +/- 0.05, 0.79 +/- 0.05). Genetic correlations indicated that pigs
      that engaged in reciprocal fighting delivered NRA to other animals (r(g) = 0.84
      +/- 0.04) but were less likely to receive NRA themselves (r(g) = -0.41 +/- 0.14).
      A genetic merit index using lesions to the anterior region as one trait and those
      to the center or rear or both as a second trait should allow selection against
      animals involved in reciprocal fighting and the delivery of NRA. Positive
      correlations between LC 24 h and 3 wk after mixing were found, especially for
      lesions to the center and rear of the body, indicating that postmixing lesions
      are predictive of those received under more stable group conditions. As well as
      reducing immediate aggression at mixing, selection on postmixing LC is expected
      to have a long-term impact on injuries from aggression, even after dominance
      relationships are established.

PMID- 19574575
TI  - Risk of subacute ruminal acidosis in sheep with separate access to forage and
      concentrate.
AB  - This study aimed to investigate whether sheep offered free-choice intake of
      forage and concentrate develop subacute ruminal acidosis (SARA) and to identify
      SARA-associated feeding behavior components. In a crossover design over two 28-d
      periods, 11 rumen-cannulated wethers received wheat and alfalfa hay in 2 separate
      compartments. Concentrate and forage were provided for ad libitum access or in a
      fixed amount corresponding to 80% of ad libitum hay intake with a
      concentrate:forage ratio of 60:40 on a DM basis. In both diets, sheep were fed 2
      equal portions at 0800 and 1600 h. Ruminal pH, voluntary intake, and feeding
      behavior were recorded continuously from d 1 to 9 and d 15 to 23 in each period.
      When no measurements were performed, the animals were housed in larger pens with
      straw bedding. When fed for ad libitum intake, the sheep ingested 1,340 g of DM/d
      consisting of 49.1% wheat, whereas with the fixed diet they ate 872 g of DM/d
      consisting of 58.4% wheat. Sheep fed for ad libitum intake spent more time with
      ruminal pH < 5.6 than when fed in fixed amounts (7.77 vs. 3.05 h/d, P < 0.001).
      The time spent with ruminal pH <5.6 was mainly linked to the amount of feed
      ingested and especially the amount of wheat (P < 0.001). Our results suggest that
      when fed for ad libitum intake with free choice wheat, the achieved
      concentrate:forage ratio of near 50:50 and a larger hay intake enable sheep to
      consume more wheat. When sheep were fed for ad libitum intake, feeding bouts were
      spread evenly throughout the day. Although ruminal pH reached the same minimum
      level in both diets after main meals, time to reach pH nadir was longer with ad
      libitum diet (P < 0.001). In addition, after reaching this minimum value, ruminal
      pH increased more slowly in this diet, inducing a decreased preprandial ruminal
      pH (P < 0.001). Consequently, the ad libitum diet led to a longer time below pH
      5.6. A slow decrease in ruminal pH may enable sheep to consume larger quantities
      of food. However, free access to concentrate maintains continuously elevated
      content of ruminal fermentation end products and so requires more time for pH to
      return to neutral values. Thus, interval between feed distributions should be as
      large as possible to help resume the preprandial ruminal pH and to limit time
      spent with pH <5.6.

PMID- 19574574
TI  - Effects of feeding zilpaterol hydrochloride for twenty to forty days on carcass
      cutability and subprimal yield of calf-fed Holstein steers.
AB  - Zilpaterol hydrochloride (ZH) is designed to increase carcass leanness, chilled
      side weight (CSW), and percent saleable yield. The objective of this study was to
      evaluate the effect of a single dose of ZH on cutability and subprimal yield of
      calf-fed Holstein steers when fed for increasing durations. Two hundred forty
      steers were fed 8.3 mg/kg of ZH on a DM basis for 0, 20, 30, or 40 d, with a 3-d
      withdrawal before slaughter. After slaughter, steers were fabricated into 4
      pieces (round, loin/flank, rib/plate, and chuck), packaged in combos, shipped to
      2 locations, and further fabricated into subprimal pieces and trim. Trim was
      collected from each primal and separated into groups based on composition of 90,
      80, and 50% lean. Zilpaterol hydrochloride increased (P = 0.01) CSW by 6.22 kg
      and saleable yield by 6.4 kg when included in the diet for 20 d. Furthermore,
      saleable yield as a percentage of CSW was increased (P = 0.03) 1.18 percentage
      units when included in the diet for 20 d. Steers fed ZH for 20 d had heavier
      strip loins (4.47 vs. 4.12 kg, P = 0.02), tenderloins (2.75 vs. 2.49 kg, P =
      0.02), and ribeye rolls (5.74 vs. 5.30 kg, P = 0.01) than steers not fed ZH.
      These advantages are further demonstrated as a percentage of CSW. Strip loins (P
      = 0.06), tenderloins (P = 0.04), and ribeye rolls (P = 0.04) of ZH-fed steers had
      a greater percentage of CSW than controls. Zilpaterol hydrochloride also
      increased the percentage of CSW of the 3 primary components of the round when fed
      for 20 d. The knuckle was 0.10 percentage units heavier (P = 0.11), the top round
      was 0.24 percentage units heavier (P = 0.04), and the bottom round was 0.22
      percentage units heavier (P = 0.03) in ZH-fed steers when compared with steers
      not fed ZH. Based on these data, it can be concluded that ZH significantly
      increased subprimal cutting weights, yields, and percentage saleable yield of
      calf-fed Holstein steers when fed for at least 20 d before slaughter. Zilpaterol
      hydrochloride increased percentage of CSW of subprimal cuts from Holstein steers
      in the round and to a lesser degree in the loin.

PMID- 19574576
TI  - Predicting milk and forage intake of nursing calves.
AB  - A theoretical model was developed to predict forage intake of nursing calves
      based on peak milk level (PML) and BW using data from 39 Holstein steer calves
      individually fed for 200 d with milk replacer reconstituted to equal the fat and
      protein contents of beef cow milk. Treatment levels were amounts of reconstituted
      milk allowed per day based on lactation curves, which were based on PML of 2.72,
      5.44, 8.16, 10.88, and 13.6 kg/d, respectively. Chopped alfalfa hay was offered
      for ad libitum intake to allow maximum voluntary forage consumption in addition
      to the reconstituted milk. We observed that calves receiving increased amounts of
      milk (10.88 to 13.66 kg of milk/d at peak) consumed little forage during the
      first 60 d of age. Their consumption of forage was also less than those calves
      receiving reduced quantities of milk (2.72 to 5.44 kg of peak milk/d) at the same
      BW because milk intake was prioritized. The forage DMI of the calf depended on
      calf BW and quality of the forage. Furthermore, calf BW and forage DMI was
      correlated with calf milk intake. A significant (P < 0.05) relationship between
      total DE intake (DEI) and BW was identified. A theoretical model was developed to
      predict forage DMI of nursing calves based on total DEI. The total DEI was
      estimated using PML and BW. Equations were developed to adjust forage DMI for DE
      content of the forage. A sensitivity analysis using Monte Carlo simulation
      indicated that forage DMI of grazing, nursing calves is likely to be less than
      4.26 kg/d 95% of the time and that variation in BW and PML have the greatest
      impact on forage DMI. We concluded that equations developed in this study can be
      used to evaluate different cow-calf production scenarios, including matching
      forage quality and availability with dam milk production potential.

PMID- 19574578
TI  - Agenesis of the corrugator supercilii: a benign condition.
AB  - We report 2 neonates with frontonasal masses. The frontonasal masses were only
      present while the neonates were crying. The rest of the general examination and
      the neurological examination of the neonates were normal. The first patient had
      an extensive neuroimaging evaluation that included skull radiograph, computed
      tomography (CT) and magnetic resonance imaging (MRI) of the brain, and ultrasound
      of the frontonasal mass. The second patient was evaluated with ultrasound of the
      frontonasal mass. The mother of the second patient had no frontonasal creases and
      was unable to frown. In both patients, the ultrasonographic studies revealed
      nonspecific soft tissue thickening in the region of the glabella only while
      crying. The ultrasonographic findings and the similarity between the mother's
      findings and those of adult patients receiving botulinum toxin injection to the
      corrugator supercilii muscle point to the absence of this muscle as the cause of
      the frontonasal mass in these patients.

PMID- 19574579
TI  - Neurologic outcome in neonatal temporal lobe hemorrhagic venous infarcts.
AB  - Consequences of neonatal cerebral venous infarct can be severe. However, we have
      identified a series of neonates with unilateral temporal lobe infarcts, suspected
      to be secondary to superficial cortical venous thrombosis, who have had
      relatively normal outcomes. Medical records were reviewed retrospectively.
      History, relevant studies, and outcomes for 7 patients are described. Most
      patients presented with neonatal seizures. Neuroimaging showed unilateral
      temporal lobe hemorrhage and surrounding ischemic change, which was initially
      attributed to thrombosis of the vein of Labbe; however, magnetic resonance
      venogram findings suggest that thrombosis of other superficial temporal lobe
      veins may also be involved. Seizure control was achieved in all cases.
      Development and neurologic examination at follow-up were usually normal. We
      conclude that neonatal temporal lobe hemorrhagic infarct secondary to suspected
      superficial temporal venous thrombosis appears to have a good clinical outcome.
      This is surprising, given the dramatic imaging and clinical presentations.

PMID- 19574580
TI  - Klebsiella pneumoniae brain abscess in neonates: a report of 2 cases.
AB  - Brain abscesses are uncommon in neonates. Klebsiella pneumoniae is a very
      uncommon microbial agent to cause brain abscess. We report 2 infants with
      Klebsiella pneumoniae sepsis who developed brain abscesses. One infant was a
      premature neonate who required mechanical ventilation for respiratory distress
      syndrome and subsequently developed nosocomial sepsis and brain abscess without
      evidence of preceding meningitis. Another infant was a full-term neonate without
      risk factors for sepsis who developed seizures on the sixth postnatal day and was
      found to have meningitis and brain abscess. Both infants had Klebsiella
      pneumoniae septicemia with multiple relatively large brain abscesses that
      responded poorly to antimicrobial agents. These infants were managed with
      transfontanel drainage and prolonged courses of antimicrobial agents. Key message
      of this report is that Klebsiella pneumoniae brain abscess may occur in the
      absence of meningitis and even in the absence of any identifiable risk factors.

PMID- 19574577
TI  - Apoptotic mechanisms in the immature brain: involvement of mitochondria.
AB  - Brain injury after hypoxic-ischemic encephalopathy often develops with delayed
      appearance, opening a therapeutic window. Clinical studies in newborns show that
      post-hypoxic-ischemic hypothermia improves outcome. This has generated renewed
      interest in the molecular mechanisms of hypoxic-ischemic brain injury. In this
      brief review, we propose that mitochondrial permeabilization is crucial for
      injury to advance beyond the point of no return. We suggest that excitatory amino
      acids, nitric oxide, inflammation, trophic factor withdrawal, and an increased
      pro- versus antiapoptotic Bcl-2 protein ratio will trigger Bax-dependent
      mitochondrial outer membrane permeabilization. Mitochondrial outer membrane
      permeabilization, in turn, elicits mitochondrial release of cytochrome C,
      apoptosis-inducing factor, second mitochondria-derived activator of
      caspase/Diablo, and HtrA2/Omi. Cytochrome C efflux activates caspase-9/-3,
      leading to DNA fragmentation. Apoptosis-inducing factor interacts with
      cyclophilin A and induces chromatinolysis. Blockage of mitochondrial outer
      membrane permeabilization holds promise as a strategy for perinatal brain
      protection.

PMID- 19574583
TI  - Guerilla advocacy: using aggressive marketing techniques for health policy
      change.

PMID- 19574581
TI  - An unusual homozygous arylsulfatase: a pseudodeficiency in a metachromatic
      leukodystrophy Tunisian patient.
AB  - Metachromatic leukodystrophy is an autosomal recessive neurodegenerative
      lysosomal disease characterized by a deficiency of the lysosomal enzyme
      arylsulfatase A and the subsequent accumulation of sulfatide in neuronal and
      visceral tissues. Clinical diagnosis is usually confirmed by in vitro analysis of
      arylsulfatase A activity but may be complicated in cases of arylsulfatase A
      pseudodeficiency and sphingolipid activators protein deficiency. We report the
      case of a 3-year-old boy who presented a severe form of late infantile
      metachromatic leukodystrophy. This patient was found to be homozygous for the
      arylsulfatase A pseudodeficiency. This condition is rare and can lead to a severe
      disease. Prenatal diagnosis was performed in this family, and the fetus was
      healthy.

PMID- 19574584
TI  - Ethics and patient education: health literacy and cultural dilemmas.
AB  - This article discusses health literacy and cultural factors that have
      implications for the ethical practice of health education. It specifically
      focuses on recent data that speaks to the challenges in carrying out patient
      education from the perspective of comprehension and equitable distribution of
      health-related information across diverse cultures and communities. It discusses
      strategies for reducing the negative impact of low health literacy among diverse
      groups and the importance of acknowledging this pervasive problem in the context
      of ensuring equity in the optimal delivery of health promotion messages.

PMID- 19574585
TI  - Associate editors' foreword: entrepreneurship in health education and health
      promotion: five cardinal rules.
AB  - A career in health education or health promotion (HE/HP) can be developed in many
      ways. In past editions of this department, career development has been discussed
      in relation to distance (Balonna, 2001), consulting (Bookbinder, 2001),
      certifications (Hayden, 2005), graduate school (Cottrell & Hayden, 2007), and
      many other topics. This article looks at a less traditional means of career
      development-entrepreneurship. Health education is a field ripe with opportunities
      for consulting and for selling health-related products and services.
      Entrepreneurship can not only create financial rewards but can also provide high
      visibility and networking contacts that can advance one's career. This article
      combines both theory and practical applications to assist readers in developing
      entrepreneurial activities. The authors are experienced in entrepreneurial
      development and use that expertise to provide relevant examples and develop a
      framework using "five cardinal rules" for establishing an entrepreneurial
      enterprise in HE/HP.

PMID- 19574586
TI  - Examining the role of training in evidence-based public health: a qualitative
      study.
AB  - The use of evidence-based public health (EBPH) approaches is generally recognized
      as essential to changing public health outcomes. However, using an EBPH decision
      making process requires public health practitioners to have the skills to review
      the evidence and pick the most workable strategy to address the problem at hand
      for their population of interest and the local context. Although there has been a
      growing body of academic literature examining the skills needed to translate
      evidence-based programs in local settings, many public health practitioners have
      not had the opportunity to learn or develop these skills. This article reports on
      qualitative interviews conducted to evaluate the process and impact of an EBPH
      course. The course has been found to assist participants in integrating new and
      existing skills to make evidence-based decisions. However, participants emphasize
      that factors external to the course influence their ability to engage in the EBPH
      process they learned.

PMID- 19574587
TI  - In the dark: young men's stories of sexual initiation in the absence of relevant
      sexual health information.
AB  - A growing body of research has investigated the effectiveness of abstinence-only
      sexual education. There remains a dearth of research on the relevant sexual
      health information available to young men who have sex with men (YMSM). Drawing
      on a mixed-methods study with 526 YMSM, this study explores how and where YMSM
      receive relevant information on sexual health/behavior. Findings indicate that
      information related to gay men's sexuality is not readily available from family,
      friends, or schools. At initiation of anal intercourse, respondents generally had
      limited information about HIV and sexually transmitted infections (STIs). In some
      cases, this resulted in the perception that activities such as unprotected sex
      were "low risk." Many mentioned they first learned about anal sex during their
      sexual debut, describing painful and/or unpleasant experiences. Some relied on
      older/more experienced partners, the Internet, and pornography for information.
      Findings are discussed in relation to how providers can help YMSM build solid
      foundations of sexual education to protect them from STI and HIV infection.

PMID- 19574588
TI  - Pathophysiological mechanisms of parvovirus B19 infection.

PMID- 19574589
TI  - Clinical relevance of Campylobacter concisus isolated from pediatric patients.

PMID- 19574590
TI  - Risk-management plan for opioid drugs proves slow going.

PMID- 19574591
TI  - Switches of antiepileptic drug products come under fire.

PMID- 19574594
TI  - One-year follow-up on procedure to prevent i.v. drug incompatibilities in an
      intensive care unit.

PMID- 19574593
TI  - Drug counterfeiting burden remains a guess, experts say.

PMID- 19574595
TI  - Incompatibility of imipenem-cilastatin and amoxicillin.

PMID- 19574596
TI  - Interpreting data about prolongation of the Q-Tc interval induced by amiodarone
      and haloperidol.

PMID- 19574597
TI  - Pharmacists and pharmacogenetics.

PMID- 19574598
TI  - More on pharmacogenomics and warfarin.

PMID- 19574599
TI  - Development of a collaborative knowledge base tool in a hospital pharmacy
      department.

PMID- 19574600
TI  - Understanding research principles: giving our patients the care they deserve.

PMID- 19574601
TI  - Alvimopan for postoperative ileus.
AB  - PURPOSE: The efficacy, safety, pharmacology, pharmacokinetics, drug-drug
      interactions, and administration of alvimopan for postoperative ileus are
      reviewed. SUMMARY: Alvimopan is a selective mu-opioid receptor antagonist with no
      central nervous system activity. When orally administered after partial small- or
      large-bowel resection in patients with primary anastomosis, alvimopan shortened
      the return of bowel function and time to discharge by approximately one day
      without compromising analgesia. Alvimopan was not shown to be beneficial on these
      same outcomes after hysterectomy and has not been studied in other surgical
      populations. Alvimopan is generally well tolerated, with the frequency of adverse
      events being similar to placebo when used postoperatively for one week or less.
      Long-term studies of alvimopan in opioid-induced bowel dysfunction have shown an
      association with adverse cardiovascular outcomes, neoplasms, and fractures.
      Because of these concerns, the Entereg Access Support and Education program was
      developed. The recommended dosage of alvimopan is 12 mg administered with a sip
      of water 30 minutes to five hours before surgery, followed by 12 mg twice daily
      beginning the day after surgery for a maximum of seven days, 15 total doses, or
      until discharge. There is a limited amount of pharmacoeconomic analysis
      concerning alvimopan. CONCLUSION: Alvimopan, a peripherally acting mu-opioid
      receptor antagonist, is a novel agent for the treatment of postoperative ileus.
      It appears to decrease the duration of postoperative ileus and hospitalization by
      approximately one day, theoretically offsetting its acquisition costs. Unresolved
      long-term safety issues, a limited indication, and its restricted-access program
      are likely to hinder its widespread use in the surgical population.

PMID- 19574602
TI  - Comparative effectiveness research: Relevance and applications to pharmacy.
AB  - PURPOSE: An overview of the emerging field of comparative effectiveness research
      (CER) and its relevance to pharmacists and pharmacy-based decision-makers is
      provided. SUMMARY: The U.S. government is investing over $1 billion on CER over
      the next two years. This investment is in part driven by the recognition that,
      despite having the highest per capita health care expenditures in the world, the
      United States does not always perform well on measures of health compared with
      other countries. There also is increased awareness of the limited information
      provided by results of traditional randomized clinical trials to inform decisions
      about therapeutic alternatives as applied in actual practice. Comparative
      effectiveness studies have two important principal components: (1) the comparison
      of two or more agents or interventions that are considered true therapeutic
      alternatives and (2) the examination of effects (outcomes) in actual practice.
      Comparative effectiveness studies differ from traditional efficacy studies in
      several ways, including the research question addressed, comparison groups,
      patient population, setting, outcomes measured, and validity. Studies that are
      within the scope of CER can be categorized as primary comparative effectiveness
      studies or secondary comparative effectiveness studies. CER also can be used to
      compare medical devices, procedures, health services, or any competing
      intervention. CONCLUSION: Comparative effectiveness is an emerging area of
      research relevant to many areas of health care, especially pharmacotherapy. The
      knowledge gained from CER is important to pharmacists when applying drug
      information and making decisions related to drug therapy.

PMID- 19574603
TI  - Acyclovir-induced renal failure in an obese patient.
AB  - PURPOSE: A case of acyclovir-induced acute renal failure in an obese patient is
      described. SUMMARY: A 60-year-old white man arrived at the emergency department
      complaining of confusion and disorientation. He was 5 ft 7 in tall and weighed
      108.9 kg. His medical and surgical histories included chronic obstructive
      pulmonary disease (COPD), sleep apnea not requiring biphasic positive airway
      pressure, obesity, oxygen supplementation, and appendectomy. He also had a
      history of cyst drainage on the back of his neck, with recent drainage emitting a
      foul odor, and suffered recurrent herpes cold sores on his chin. A lumbar
      puncture revealed abnormal cerebral spinal fluid. A diagnosis of herpes
      encephalitis was considered, and the patient was empirically treated with i.v.
      acyclovir 1 g over 60 minutes every eight hours, with the dosage based on actual
      body weight. He was also given moxifloxacin 400 mg i.v. daily for possible COPD
      exacerbation and doxycycline 100 mg i.v. twice daily for possible leptospirosis
      meningitis. On hospital day 3, his serum creatinine (SCr) and blood urea nitrogen
      (BUN) concentrations rose to 2.8 g/dL and 32 mg/dL, respectively. Acyclovir was
      subsequently discontinued, as were all i.v. antibiotics. On day 7, hydration
      therapy was initiated, as was therapy to alkalinize the urine, and his neurologic
      status began to improve. At discharge, the patient's SCr and BUN levels were 3.1
      g/dL and 38 mg/dL, respectively. His discharge diagnoses included encephalitis
      with possible viral origin and acyclovir-induced nephrotoxicity. CONCLUSION: An
      obese man receiving excessive doses of i.v. acyclovir developed acute but
      reversible renal failure.

PMID- 19574604
TI  - Tenfold therapeutic dosing errors in young children reported to U.S. poison
      control centers.
AB  - PURPOSE: Tenfold dosing medication errors reported to U.S. poison control centers
      in children younger than six years of age were evaluated. METHODS: A
      retrospective review of all exposures in children younger than six years of age
      reported to the American Association of Poison Control Centers' data collection
      system during 2000-04 was conducted. Cases were selected for inclusion if the
      exposure was an unintentional therapeutic error and if 10-fold dosing error was
      coded as one of the therapeutic-error scenarios. The specific substance or drug
      category, patient age and sex, site of exposure, clinical effects, disposition,
      and outcome were evaluated RESULTS: A total of 3894 10-fold dosing errors
      involving a single substance in children younger than six years of age were
      reported over a five-year period. The site of exposure was most commonly a
      residence (n = 3609, 92.7%), followed by a health care facility (n = 223, 5.7%)
      and a school (n = 32, 0.8%). More than half of the exposures occurred in children
      12 months of age or younger. When stratified by age, histamine H(2)- receptor
      antagonists and metoclopramide were the most common medications involved in
      exposures in children 12 months of age and younger. Cough and cold preparations
      and antibiotics were the most commonly involved medications in therapeutic errors
      in children over age 12 months. CONCLUSION: The most common substances involved
      in 10-fold medication errors reported to U.S. poison control centers were
      histamine H(2)-receptor antagonists and metoclopramide. Most exposures occurred
      in the home and involved children 12 months of age or younger.

PMID- 19574605
TI  - Implementation of a collaborative drug therapy management service for inpatients
      receiving direct thrombin inhibitors.
AB  - PURPOSE: The development and implementation of a collaborative drug therapy
      management (CDTM) service for inpatients receiving direct thrombin inhibitors
      (DTIs) are described. SUMMARY: A pharmacist-driven DTI protocol was established
      to help establish guidelines for the use and monitoring of DTIs to ensure the
      effective and safe administration of these high-risk medications. The CDTM
      service and DTI dosing protocol, including order form development, were completed
      over a two-year period. The DTI order form consisted of five main sections:
      practice points pertaining to the clinical diagnosis of heparin-induced
      thrombocytopenia (HIT), initiation of DTIs, nurse- and pharmacist-driven
      instructions for the monitoring of DTI therapy, information to safely transition
      a patient from a DTI to warfarin, and a scoring system for determining the
      probability of HIT. A CDTM service for the inpatient setting was developed to
      improve patient outcomes and reduce medication errors related to the monitoring
      and adjusting of DTI dosages. To implement this service, three major areas were
      addressed: the credentialing of pharmacists, the ordering process, and required
      documentation. Challenges encountered during protocol development were
      eliminating the use of lepirudin, developing a comprehensive order form for two
      DTIs, obtaining approval of the DTI dosing protocol by the medical executive
      committee, and developing and implementing a comprehensive nursing education
      program for the new order form and protocol. CONCLUSION: A dosing protocol for
      DTIs was developed to improve the use of these high-risk medications within an
      institution. The protocol provided physicians with the option of deferring DTI
      dosing to a pharmacist with appropriate credentials.

PMID- 19574606
TI  - Implementing an electronically based, nurse-driven pneumococcal vaccination
      protocol for inpatients.
AB  - PURPOSE: The development and implementation of an electronically based, nurse
      driven pneumococcal vaccination protocol for hospitalized patients are described.
      SUMMARY: A multidisciplinary team was formed to address the development,
      implementation, and management of an automatic pneumococcal vaccination program.
      Screening of patients was performed by the nursing staff on admission to the
      hospital; the screening process was streamlined using computer-generated
      assessment forms. The electronic program enabled systematic identification of
      patients eligible for vaccination, standardization of vaccine order instructions,
      documentation of vaccinations in a centralized electronic database, automatic
      documentation of vaccinations on patients' discharge instructions, and collection
      of vaccination data for future analysis. If vaccination was indicated, an
      electronic order was automatically generated for the vaccine to be administered
      within 24 hours. The electronic order appeared on the electronic medication
      administration record like any other medication. Given the prominent role of
      nursing in the protocol, the largest training effort was in the nursing
      department, with education targeting 1200 nurses. Precautions were taken to
      minimize unintended duplicate vaccine administration. Patients were excluded from
      the vaccination protocol if they were younger than age 65 years, had a fever,
      were still in an intensive care unit, had an acute neurologic disorder, or had
      any condition for which there was doubt about the safety or appropriateness of
      the vaccination. Multidisciplinary resources are used to further reevaluate and
      refine the vaccine protocol. CONCLUSION: A multidisciplinary team successfully
      developed and implemented an electronically based, nurse-driven pneumococcal
      vaccination protocol for hospitalized patients in a teaching hospital.

PMID- 19574608
TI  - Electronic prescribing of controlled substances.

PMID- 19574607
TI  - Alvimopan for postoperative ileus: only one piece of the puzzle.

PMID- 19574609
TI  - Summary of the Proceedings of the 2008 ASHP National Residency Preceptors
      Conference.

PMID- 19574610
TI  - Influence of a fed or fasted state on the s-IgA response to prolonged cycling in
      active men and women.
AB  - This study investigated the effect of a fed or fasted state on the salivary
      immunoglobulin A (s-IgA) response to prolonged cycling. Using a randomized,
      crossover design, 16 active adults (8 men and 8 women) performed 2 hr of cycling
      on a stationary ergometer at 65% of maximal oxygen uptake on 1 occasion after an
      overnight fast (FAST) and on another occasion 2 hr after consuming a 2.2-MJ high
      carbohydrate meal (FED). Timed, unstimulated whole saliva samples were collected
      immediately before ingestion of the meal, immediately preexercise, 5 min before
      cessation of exercise, immediately postexercise, and 1 hr postexercise. The
      samples were analyzed for s-IgA concentration, osmolality, and cortisol, and
      saliva flow rates were determined to calculate s-IgA secretion rate. Saliva flow
      rate decreased by 50% during exercise (p < .05), and s-IgA concentration
      increased by 42% (p < .05), but s-IgA secretion rate remained unchanged. There
      was a 37% reduction in s-IgA:osmolality postexercise (p < .05), and salivary
      cortisol increased by 68% (p < .05). There was no effect of FED vs. FAST on these
      salivary responses. The s-IgA concentration, secretion rate, and osmolality were
      found to be significantly lower in women than in men throughout the exercise
      protocol (p < .05); however, there was no difference between genders in saliva
      flow rate, s-IgA:osmolality ratio, or cortisol. These data demonstrate that a fed
      or fasted state 2 hr before exercise does not influence resting s-IgA or the
      response to prolonged cycling. Furthermore, these results show lower levels of s
      IgA and osmolality in women than in men at rest.

PMID- 19574611
TI  - Effect of preexercise glycemic-index meal on running when CHO-electrolyte
      solution is consumed during exercise.
AB  - PURPOSE: This study examined the effect of consuming carbohydrate- (CHO)
      electrolyte solution on running performance after different-glycemic-index (GI)
      meals. METHODS: Nine men completed 3 trials in a randomized counterbalanced
      order, with trials separated by at least 7 days. Two hours before the run after
      an overnight fast, each participant consumed a high-GI (GI = 83) or low-GI (GI =
      36) CHO meal or low-energy sugar-free Jell-O (GI = 0, control). The 2 isocaloric
      GI meals provided 1.5 g available CHO/kg body mass. During each trial, 2 ml/kg
      body mass of a 6.6% CHO-electrolyte solution was provided immediately before
      exercise and every 2.5 km after the start of running. Each trial consisted of a
      21-km performance run on a level treadmill. The participants were required to run
      at 70% VO2max during the first 5 km of the run. They then completed the remaining
      16 km as fast as possible. RESULTS: There was no difference in the time to
      complete the 21-km run (high-GI vs. low-GI vs. control: 91.1 +/- 2.0 vs. 91.8 +/-
      2.2 vs. 92.9 +/- 2.0 min, n.s.). There were no differences in total CHO and fat
      oxidation throughout the trials, despite differences in preexercise blood
      glucose, serum insulin, and serum free-fatty-acid concentrations. CONCLUSION:
      When a CHO-electrolyte solution is consumed during a 21-km run, the GI of the
      preexercise CHO meal makes no difference in running performance.

PMID- 19574612
TI  - A soccer match's ability to enhance lymphocyte capability to produce ROS and
      induce oxidative damage.
AB  - Soccer-associated oxidative stress has barely been studied. The aims of this
      study were to establish the effect of a soccer training match and the effect of a
      diet supplementation with a multivitamin complex and coenzyme Q during 3 months
      of soccer training on the pro-oxidant and antioxidant status of lymphocytes. In a
      randomized, double-blind trial, 19 male preprofessional soccer players were
      treated with either an antioxidant nutrient cocktail or placebo for 90 days.
      After this period the athletes played a soccer match lasting 60 min. All
      determinations were made under basal conditions before and after the training
      period and after the match. Basal lymphocyte hydrogen peroxide (H2O2) production
      did not change after the 3 months of training. Catalase activity decreased (about
      50%) after the 3 months, whereas glutathione reductase increased its activity
      (150-200%) both with placebo and in the supplemented group. Basal ascorbate
      levels were maintained during the training period, whereas a-tocopherol and MDA
      decreased (about 40%) in both groups. The match increased H2O2 production (180%)
      in both groups when the lymphocytes were stimulated with phorbol myristate
      acetate, and it also increased MDA levels (150%). Antioxidant enzyme activities
      and antioxidant vitamin levels were maintained before and after the match.
      Regular soccer training modifies the lymphocyte strategy to eliminate ROS and
      increases protection against oxidative damage. A friendly soccer match raises
      lymphocyte capacity to produce ROS and oxidative damage, but it is not enough to
      induce a defensive response, thus leading to a situation of postexercise
      oxidative stress. Supplementation with low doses of antioxidant vitamins and
      coenzyme Q does not modify the endogenous antioxidant response to training.

PMID- 19574613
TI  - Comparison of fluid balance between competitive swimmers and less active
      adolescents.
AB  - The aim of this study was to compare daily hydration profiles of competitive
      adolescent swimmers and less active maturation- and sex-matched controls.
      Hydration profiles of 35 competitive adolescent swimmers (male n = 18, female n =
      17) and 41 controls (male n = 29, female n = 12) were monitored on 4 consecutive
      days. First morning hydration status was determined independently by urine
      specific gravity (USG) and urine color. Changes in fluid balance were estimated
      during the school day and in training sessions after adjusting for self-reported
      urine losses and fluid intake. Urinalyses revealed consistent fluid deficits (USG
      >1.020, urine color >or=5) independent of activity group, sex, and day of testing
      (hypohydration in 73-85% of samples, p > .05). Fluid balance and intake were
      observed over typical school days in males and females from the 2 groups. During
      training, male swimmers lost more fluid relative to initial body mass but drank
      no more than females. Although both activity groups began each testing day with a
      similar hydration status, training induced significant variations in fluid
      balance in the swimmers compared with controls. Despite minimal fluid losses
      during individual training sessions (<2% body mass), these deficits significantly
      increased fluid needs for young swimmers over the school day.

PMID- 19574614
TI  - No placebo effect from carbohydrate intake during prolonged exercise.
AB  - The purpose of this study was to investigate the possibility of a placebo effect
      from carbohydrate (CHO) intake during prolonged exercise. Ten endurance-trained
      male cyclists performed 3 experimental trials consisting of 120 min of steady
      state cycling at 61% VO2max followed by a time trial (TT) lasting approximately
      60 min. During exercise participants ingested either plain water (WAT),
      artificially colored and flavored water (PLA), or a 6% carbohydrate-electrolyte
      solution (CES). PLA and CES were produced with identical color and taste. To
      investigate the possibility of a placebo effect from CHO intake, participants
      were told that both flavored solutions contained CHO and that the purpose of the
      study was to compare CHO drinks with water. Mean power output during TT was 218
      +/- 22 W in WAT, 219 +/- 17 W in PLA, and 242 +/- 27 W in CES. Performance times
      were 66.35 +/- 6.15, 65.94 +/- 5.56, and 59.69 +/- 2.87 min for WAT, PLA, and
      CES, respectively. Therefore, CES ingestion enhanced TT performance by 11.3%
      compared with WAT (p < .05) and 10.6% compared with PLA (p < .05), with no
      difference between PLA and WAT. In conclusion, during a prolonged test of cycling
      performance, in which participants were not fully informed of the test
      conditions, there was no placebo effect when participants believed they had
      ingested CHO. In contrast, the real effect of CHO intake was a 10.6% improvement
      in TT cycling performance.

PMID- 19574615
TI  - L-cysteine's effect on modulated rat brain enzymes with forced swimming.
AB  - BACKGROUND: Forced exercise is associated with oxidative stress, and L-cysteine
      (L-cys) administration reduces free-radical production. AIM: To investigate
      whether L-cys (5 mg/kg) intraperitoneal administration can ameliorate modulated
      total antioxidant status (TAS), protein concentration, and the activities of
      acetylcholinesterase (AChE), (Na+,K+)-ATPase, and Mg2+-ATPase in rat brain after
      2 and 3 hr of forced swimming. METHODS: TAS, protein, and enzyme activities were
      measured spectrophotometrically before and after 2 and 3 hr of exercise without
      or with L-cys administration. RESULTS: TAS concentration (55.6 +/- 1.5 vs. 42.1
      +/- 1.0 vs. 37.4 +/- 1.2 micromol/L, p < .001), protein concentration (5.68 +/-
      0.36 vs. 5.40 +/- 0.18 vs. 4.01 +/- 0.16 mg/ml, p < .01), and AChE activity (0.89
      +/- 0.05 vs. 0.61 +/- 0.04 vs. 0.48 +/- 0.03 DeltaOD/min x mg protein, p < .001)
      were significantly reduced, whereas Na+,K+-ATPase (6.00 +/- 0.36 vs. 10.44 +/-
      1.04 vs. 11.90 +/- 1.21 micromol phosphorus inorganic/hr x mg protein, p < .001)
      and Mg2+-ATPase activity (7.20 +/- 0.65 vs. 10.88 +/- 1.08 vs. 11.55 +/- 1.22
      mmol phosphorus inorganic/hr x mg protein, p < .001) were statistically
      significantly increased after 2 and 3 hr of forced exercise. Post-L-cys
      administration, AChE activity was decreased (0.90 +/- 0.04 vs. 0.47 +/- 0.02
      DeltaOD/min x mg protein, p < .001) and remained unaltered (0.64 +/- 0.04 vs.
      0.67 +/- 0.04 DeltaOD/min x mg protein, p > .05) 2 and 3 hr postexercise (0.47 +/
      0.02 vs. 0.54 +/- 0.02 DeltaOD/min x mg protein, p > .05). Na+,K+-ATPase was
      decreased and remained unchanged (1.85 +/- 0.17 vs. 1.77 +/- 0.19 mumol
      phosphorus inorganic/hr x mg protein, p > .05) 2 and 3 hr postswimming (1.91 +/-
      0.19 vs. 2.06 +/- 0.17 mumol phosphorus inorganic/hr x mg protein, p > .05). Mg2+
      ATPase activity was similar with L-cys supplementation pre- vs. postswimming.
      CONCLUSIONS: L-cys administration might ameliorate modulated rat brain enzyme
      activities induced by free-radical production during forced swimming.

PMID- 19574616
TI  - Is ginseng an ergogenic aid?
AB  - Ginseng is one of the most popular herbal supplements in the world. Although it
      is used for the treatment and prevention of many ailments, it is also used to
      increase work efficiency and is purported to increase energy and physical
      stamina. Athletes use ginseng for its alleged performance-enhancing attributes.
      However, many studies examining the pharmacological effects of ginseng on
      physical performance have not employed sound scientific design and methodology.
      The purpose of this review is to provide an update on published empirical
      research focusing primarily on the efficacy of ginseng with respect to physical
      and athletic performance. Despite attempts in recent investigations to improve on
      the scientific rigor used in examining the ergogenic properties of ginseng, the
      authors conclude that many of the same methodological shortcomings observed in
      earlier studies persist. Enhanced physical performance after ginseng
      administration in well-designed investigations remains to be demonstrated.

PMID- 19574617
TI  - Factorial switching linear dynamical systems applied to physiological condition
      monitoring.
AB  - Condition monitoring often involves the analysis of systems with hidden factors
      that switch between different modes of operation in some way. Given a sequence of
      observations, the task is to infer the filtering distribution of the switch
      setting at each time step. In this paper, we present factorial switching linear
      dynamical systems as a general framework for handling such problems. We show how
      domain knowledge and learning can be successfully combined in this framework, and
      introduce a new factor (the "X-factor") for dealing with unmodeled variation. We
      demonstrate the flexibility of this type of model by applying it to the problem
      of monitoring the condition of a premature baby receiving intensive care. The
      state of health of a baby cannot be observed directly, but different underlying
      factors are associated with particular patterns of physiological measurements and
      artifacts. We have explicit knowledge of common factors and use the X-factor to
      model novel patterns which are clinically significant but have unknown cause.
      Experimental results are given which show the developed methods to be effective
      on typical intensive care unit monitoring data.

PMID- 19574618
TI  - Calibration of cameras with radially symmetric distortion.
AB  - We present algorithms for plane-based calibration of general radially distorted
      cameras. By this, we understand cameras that have a distortion center and an
      optical axis such that the projection rays of pixels lying on a circle centered
      on the distortion center form a right viewing cone centered on the optical axis.
      The camera is said to have a single viewpoint (SVP) if all such viewing cones
      have the same apex (the optical center); otherwise, we speak of NSVP cases. This
      model encompasses the classical radial distortion model [5], fisheyes, and most
      central or noncentral catadioptric cameras. Calibration consists in the
      estimation of the distortion center, the opening angles of all viewing cones, and
      their optical centers. We present two approaches of computing a full calibration
      from dense correspondences of a single or multiple planes with known euclidean
      structure. The first one is based on a geometric constraint linking viewing cones
      and their intersections with the calibration plane (conic sections). The second
      approach is a homography-based method. Experiments using simulated and a broad
      variety of real cameras show great stability. Furthermore, we provide a
      comparison with Hartley-Kang's algorithm [12], which, however, cannot handle such
      a broad variety of camera configurations, showing similar performance.

PMID- 19574619
TI  - Detection, localization, and sex classification of faces from arbitrary
      viewpoints and under occlusion.
AB  - This paper presents a novel framework for detecting, localizing, and classifying
      faces in terms of visual traits, e.g., sex or age, from arbitrary viewpoints and
      in the presence of occlusion. All three tasks are embedded in a general viewpoint
      invariant model of object class appearance derived from local scale-invariant
      features, where features are probabilistically quantified in terms of their
      occurrence, appearance, geometry, and association with visual traits of interest.
      An appearance model is first learned for the object class, after which a Bayesian
      classifier is trained to identify the model features indicative of visual traits.
      The framework can be applied in realistic scenarios in the presence of viewpoint
      changes and partial occlusion, unlike other techniques assuming data that are
      single viewpoint, upright, prealigned, and cropped from background distraction.
      Experimentation establishes the first result for sex classification from
      arbitrary viewpoints, an equal error rate of 16.3 percent, based on the color
      FERET database. The method is also shown to work robustly on faces in cluttered
      imagery from the CMU profile database. A comparison with the geometry-free bag-of
      words model shows that geometrical information provided by our framework improves
      classification. A comparison with support vector machines demonstrates that
      Bayesian classification results in superior performance.

PMID- 19574620
TI  - Evaluation of stereo matching costs on images with radiometric differences.
AB  - Stereo correspondence methods rely on matching costs for computing the similarity
      of image locations. We evaluate the insensitivity of different costs for passive
      binocular stereo methods with respect to radiometric variations of the input
      images. We consider both pixel-based and window-based variants like the absolute
      difference, the sampling-insensitive absolute difference, and normalized cross
      correlation, as well as their zero-mean versions. We also consider filters like
      LoG, mean, and bilateral background subtraction (BilSub) and nonparametric
      measures like Rank, SoftRank, Census, and Ordinal. Finally, hierarchical mutual
      information (HMI) is considered as pixelwise cost. Using stereo data sets with
      ground-truth disparities taken under controlled changes of exposure and lighting,
      we evaluate the costs with a local, a semiglobal, and a global stereo method. We
      measure the performance of all costs in the presence of simulated and real
      radiometric differences, including exposure differences, vignetting, varying
      lighting, and noise. Overall, the ranking of methods across all data sets and
      experiments appears to be consistent. Among the best costs are BilSub, which
      performs consistently very well for low radiometric differences; HMI, which is
      slightly better as pixelwise matching cost in some cases and for strong image
      noise; and Census, which showed the best and most robust overall performance.

PMID- 19574621
TI  - Linear neighborhood propagation and its applications.
AB  - In this paper, a novel graph-based transductive classification approach, called
      Linear Neighborhood Propagation, is proposed. The basic idea is to predict the
      label of a data point according to its neighbors in a linear way. This method can
      be cast into a second-order intrinsic Gaussian Markov random field framework. Its
      result corresponds to a solution to an approximate inhomogeneous biharmonic
      equation with Dirichlet boundary conditions. Different from existing approaches,
      our approach provides a novel graph structure construction method by introducing
      multiple-wise edges instead of pairwise edges, and presents an effective scheme
      to estimate the weights for such multiple-wise edges. To the best of our
      knowledge, these two contributions are novel for semi-supervised classification.
      The experimental results on image segmentation and transductive classification
      demonstrate the effectiveness and efficiency of the proposed approach.

PMID- 19574622
TI  - Looking for shapes in two-dimensional cluttered point clouds.
AB  - We study the problem of identifying shape classes in point clouds. These clouds
      contain sampled points along contours and are corrupted by clutter and
      observation noise. Taking an analysis-by-synthesis approach, we simulate high
      probability configurations of sampled contours using models learned from training
      data to evaluate the given test data. To facilitate simulations, we develop
      statistical models for sources of (nuisance) variability: 1) shape variations
      within classes, 2) variability in sampling continuous curves, 3) pose and scale
      variability, 4) observation noise, and 5) points introduced by clutter. The
      variability in sampling closed curves into finite points is represented by
      positive diffeomorphisms of a unit circle. We derive probability models on these
      functions using their square-root forms and the Fisher-Rao metric. Using a Monte
      Carlo approach, we simulate configurations from a joint prior on the shape-sample
      space and compare them to the data using a likelihood function. Average
      likelihoods of simulated configurations lead to estimates of posterior
      probabilities of different classes and, hence, Bayesian classification.

PMID- 19574623
TI  - Optimal classifier fusion in a non-bayesian probabilistic framework.
AB  - The combination of the output of classifiers has been one of the strategies used
      to improve classification rates in general purpose classification systems. Some
      of the most common approaches can be explained using the Bayes' formula. In this
      paper, we tackle the problem of the combination of classifiers using a non
      Bayesian probabilistic framework. This approach permits us to derive two linear
      combination rules that minimize misclassification rates under some constraints on
      the distribution of classifiers. In order to show the validity of this approach
      we have compared it with other popular combination rules from a theoretical
      viewpoint using a synthetic data set, and experimentally using two standard
      databases: the MNIST handwritten digit database and the GREC symbol database.
      Results on the synthetic data set show the validity of the theoretical approach.
      Indeed, results on real data show that the proposed methods outperform other
      common combination schemes.

PMID- 19574624
TI  - P3 & beyond: move making algorithms for solving higher order functions.
AB  - In this paper, we extend the class of energy functions for which the optimal
      ?alpha-expansion and ?alpha ?beta-swap moves can be computed in polynomial time.
      Specifically, we introduce a novel family of higher order clique potentials, and
      show that the expansion and swap moves for any energy function composed of these
      potentials can be found by minimizing a submodular function. We also show that
      for a subset of these potentials, the optimal move can be found by solving an st
      mincut problem. We refer to this subset as the {?cal P};n Potts model. Our
      results enable the use of powerful ?alpha-expansion and ?alpha ?beta-swap move
      making algorithms for minimization of energy functions involving higher order
      cliques. Such functions have the capability of modeling the rich statistics of
      natural scenes and can be used for many applications in Computer Vision. We
      demonstrate their use in one such application, i.e., the texture-based image or
      video-segmentation problem.

PMID- 19574625
TI  - Robust sequential data modeling using an outlier tolerant hidden Markov model.
AB  - Hidden Markov (chain) models using finite Gaussian mixture models as their hidden
      state distributions have been successfully applied in sequential data modeling
      and classification applications. Nevertheless, Gaussian mixture models are well
      known to be highly intolerant to the presence of untypical data within the
      fitting data sets used for their estimation. Finite Student's t-mixture models
      have recently emerged as a heavier-tailed, robust alternative to Gaussian mixture
      models, overcoming these hurdles. To exploit these merits of Student's t-mixture
      models in the context of a sequential data modeling setting, we introduce, in
      this paper, a novel hidden Markov model where the hidden state distributions are
      considered to be finite mixtures of multivariate Student's t-densities. We derive
      an algorithm for the model parameters estimation under a maximum likelihood
      framework, assuming full, diagonal, and factor-analyzed covariance matrices. The
      advantages of the proposed model over conventional approaches are experimentally
      demonstrated through a series of sequential data modeling applications.

PMID- 19574626
TI  - Toward accurate and fast iris segmentation for iris biometrics.
AB  - Iris segmentation is an essential module in iris recognition because it defines
      the effective image region used for subsequent processing such as feature
      extraction. Traditional iris segmentation methods often involve an exhaustive
      search of a large parameter space, which is time consuming and sensitive to
      noise. To address these problems, this paper presents a novel algorithm for
      accurate and fast iris segmentation. After efficient reflection removal, an
      Adaboost-cascade iris detector is first built to extract a rough position of the
      iris center. Edge points of iris boundaries are then detected, and an elastic
      model named pulling and pushing is established. Under this model, the center and
      radius of the circular iris boundaries are iteratively refined in a way driven by
      the restoring forces of Hooke's law. Furthermore, a smoothing spline-based edge
      fitting scheme is presented to deal with noncircular iris boundaries. After that,
      eyelids are localized via edge detection followed by curve fitting. The novelty
      here is the adoption of a rank filter for noise elimination and a histogram
      filter for tackling the shape irregularity of eyelids. Finally, eyelashes and
      shadows are detected via a learned prediction model. This model provides an
      adaptive threshold for eyelash and shadow detection by analyzing the intensity
      distributions of different iris regions. Experimental results on three
      challenging iris image databases demonstrate that the proposed algorithm
      outperforms state-of-the-art methods in both accuracy and speed.

PMID- 19574627
TI  - A unified framework for gesture recognition and spatiotemporal gesture
      segmentation.
AB  - Within the context of hand gesture recognition, spatiotemporal gesture
      segmentation is the task of determining, in a video sequence, where the gesturing
      hand is located and when the gesture starts and ends. Existing gesture
      recognition methods typically assume either known spatial segmentation or known
      temporal segmentation, or both. This paper introduces a unified framework for
      simultaneously performing spatial segmentation, temporal segmentation, and
      recognition. In the proposed framework, information flows both bottom-up and top
      down. A gesture can be recognized even when the hand location is highly ambiguous
      and when information about when the gesture begins and ends is unavailable. Thus,
      the method can be applied to continuous image streams where gestures are
      performed in front of moving, cluttered backgrounds. The proposed method consists
      of three novel contributions: a spatiotemporal matching algorithm that can
      accommodate multiple candidate hand detections in every frame, a classifier-based
      pruning framework that enables accurate and early rejection of poor matches to
      gesture models, and a subgesture reasoning algorithm that learns which gesture
      models can falsely match parts of other longer gestures. The performance of the
      approach is evaluated on two challenging applications: recognition of hand-signed
      digits gestured by users wearing short-sleeved shirts, in front of a cluttered
      background, and retrieval of occurrences of signs of interest in a video database
      containing continuous, unsegmented signing in American Sign Language (ASL).

PMID- 19574628
TI  - Multistream articulatory feature-based models for visual speech recognition.
AB  - We study the problem of automatic visual speech recognition (VSR) using dynamic
      Bayesian network (DBN)-based models consisting of multiple sequences of hidden
      states, each corresponding to an articulatory feature (AF) such as lip opening
      (LO) or lip rounding (LR). A bank of discriminative articulatory feature
      classifiers provides input to the DBN, in the form of either virtual evidence
      (VE) (scaled likelihoods) or raw classifier margin outputs. We present
      experiments on two tasks, a medium-vocabulary word-ranking task and a small
      vocabulary phrase recognition task. We show that articulatory feature-based
      models outperform baseline models, and we study several aspects of the models,
      such as the effects of allowing articulatory asynchrony, of using dictionary
      based versus whole-word models, and of incorporating classifier outputs via
      virtual evidence versus alternative observation models.

PMID- 19574629
TI  - On scene segmentation and histograms-based curve evolution.
AB  - We consider curve evolution based on comparing distributions of features, and its
      applications for scene segmentation. In the first part, we promote using cross
      bin metrics such as the Earth Mover's Distance (EMD), instead of standard bin
      wise metrics as the Bhattacharyya or Kullback-Leibler metrics. To derive flow
      equations for minimizing functionals involving the EMD, we employ a tractable
      expression for calculating EMD between one-dimensional distributions. We then
      apply the derived flows to various examples of single image segmentation, and to
      scene analysis using video data. In the latter, we consider the problem of
      segmenting a scene to spatial regions in which different activities occur. We use
      a nonparametric local representation of the regions by considering multiple one
      dimensional histograms of normalized spatiotemporal derivatives. We then obtain
      semisupervised segmentation of regions using the flows derived in the first part
      of the paper. Our results are demonstrated on challenging surveillance scenes,
      and compare favorably with state-of-the-art results using parametric
      representations by dynamic systems or mixtures of them.

PMID- 19574630
TI  - Rotational invariance based on Fourier analysis in polar and spherical
      coordinates.
AB  - In this paper, polar and spherical Fourier analysis are defined as the
      decomposition of a function in terms of eigenfunctions of the Laplacian with the
      eigenfunctions being separable in the corresponding coordinates. The proposed
      transforms provide effective decompositions of an image into basic patterns with
      simple radial and angular structures. The theory is compactly presented with an
      emphasis on the analogy to the normal Fourier transform. The relation between the
      polar or spherical Fourier transform and the normal Fourier transform is
      explored. As examples of applications, rotation-invariant descriptors based on
      polar and spherical Fourier coefficients are tested on pattern classification
      problems.

PMID- 19574631
TI  - Comments on "Plane-based optimization for 3D object reconstruction from single
      line drawings".

PMID- 19574633
TI  - The novel 2Fe-2S outer mitochondrial protein mitoNEET displays conformational
      flexibility in its N-terminal cytoplasmic tethering domain.
AB  - A primary role for mitochondrial dysfunction is indicated in the pathogenesis of
      insulin resistance. A widely used drug for the treatment of type 2 diabetes is
      pioglitazone, a member of the thiazolidinedione class of molecules. MitoNEET, a
      2Fe-2S outer mitochondrial membrane protein, binds pioglitazone [Colca et al.
      (2004), Am. J. Physiol. Endocrinol. Metab. 286, E252-E260]. The soluble domain of
      the human mitoNEET protein has been expressed C-terminal to the superfolder green
      fluorescent protein and the mitoNEET protein has been isolated. Comparison of the
      crystal structure of mitoNEET isolated from cleavage of the fusion protein (1.4 A
      resolution, R factor = 20.2%) with other solved structures shows that the CDGSH
      domains are superimposable, indicating proper assembly of mitoNEET. Furthermore,
      there is considerable flexibility in the position of the cytoplasmic tethering
      arms, resulting in two different conformations in the crystal structure. This
      flexibility affords multiple orientations on the outer mitochondrial membrane.

PMID- 19574634
TI  - Interaction of an echinomycin-DNA complex with manganese ions.
AB  - The crystal structure of an echinomycin-d(ACGTACGT) duplex interacting with
      manganese(II) was solved by Mn-SAD using in-house data and refined to 1.1 A
      resolution against synchrotron data. This complex crystallizes in a different
      space group compared with related complexes and shows a different mode of base
      pairing next to the bis-intercalation site, suggesting that the energy difference
      between Hoogsteen and Watson-Crick pairing is rather small. The binding of
      manganese to N7 of guanine is only possible because of DNA unwinding induced by
      the echinomycin, which might help to explain the mode of action of the drug.

PMID- 19574635
TI  - Structure of the lamin A/C R482W mutant responsible for dominant familial partial
      lipodystrophy (FPLD).
AB  - Proteins of the A-type lamin family, which consists of two members, lamin A and
      lamin C, are the major components of a thin proteinaceous filamentous meshwork,
      the lamina, that underlies the inner nuclear membrane. A-type lamins have
      recently become the focus of extensive functional studies as a consequence of the
      linking of at least eight congenital diseases to mutations in the lamin A/C gene
      (LMNA). This spectrum of pathologies, which mostly manifest themselves as
      dominant traits, includes muscle dystrophies, dilated cardiomyopathies, the
      premature aging syndrome Hutchinson-Guilford progeria and familial partial
      lipodystrophy (FPLD). The crystal structure of the lamin A/C mutant R482W, a
      variant that causes FPLD, has been determined at 1.5 A resolution. A completely
      novel aggregation state of the C-terminal globular domain and the position of the
      mutated amino-acid residue suggest means by which the mutation may affect lamin
      A/C-protein and protein-DNA interactions.

PMID- 19574636
TI  - Inhibitor design for ribonuclease A: the binding of two 5'-phosphate uridine
      analogues.
AB  - In the quest for the rational design of selective and potent inhibitors for
      members of the pancreatic ribonuclease A (RNase A) family of biomedical interest,
      the binding of uridine 5'-phosphate (U5P) and uridine 5'-diphosphate (UDP) to
      RNase A have been investigated using kinetic studies and X-ray crystallography.
      Both nucleotides are competitive inhibitors of the enzyme, with K(i) values of
      4.0 and 0.65 mM, respectively. They bind to the active site of the enzyme by
      anchoring two molecules connected to each other by hydrogen bonds and van der
      Waals interactions. While the first of the inhibitor molecules binds with its
      nucleobase in the pyrimidinyl-binding subsite, the second is bound at the purine
      preferring subsite. The unexpected binding of a pyrimidine at the purine-binding
      subsite has added new important elements to the rational design approach for the
      discovery of new potent inhibitors of the RNase A superfamily.

PMID- 19574637
TI  - Crystallization and preliminary crystallographic analysis of bifunctional gamma
      glutamylcysteine synthetase-glutatione synthetase from Streptococcus agalactiae.
AB  - gamma-Glutamylcysteine synthetase-glutathione synthetase (gammaGCS-GS) is a
      bifunctional enzyme that catalyzes two consecutive steps of ATP-dependent peptide
      formation in glutathione biosynthesis. Streptococcus agalactiae gammaGCS-GS is a
      target for the development of potential therapeutic agents. gammaGCS-GS was
      crystallized using the sitting-drop vapour-diffusion method. The crystals grew to
      dimensions of 0.3 x 0.2 x 0.2 mm under reducing conditions with 5 mM TCEP. X-ray
      data were collected to 2.8 A resolution from a tetragonal crystal that belonged
      to space group I4(1).

PMID- 19574638
TI  - Purification, crystallization and preliminary X-ray analysis of haemoglobin from
      ostrich (Struthio camelus).
AB  - Haemoglobin is a tetrameric protein that carries oxygen from the lungs to tissues
      and carbon dioxide from tissues back to the lungs. The oxygen-binding properties
      of haemoglobin are regulated through the binding of allosteric effectors. The
      respiratory system of avian species is unique and complex in nature when compared
      with that of mammals. In avian species, inositol pentaphosphate (inositol-P(5))
      is present in the erythrocytes of the adult and is thought to be the major factor
      responsible for the relatively high oxygen affinity of the whole blood. The
      ostrich (Struthio camelus) is a large flightless bird which contains inositol
      tetrakisphosphate (inositol-P(4)) in its erythrocytes and its whole blood oxygen
      affinity is higher. Efforts have been made to explore the structure-function
      relationship of ostrich haemoglobin. Ostrich haemoglobin was purified using ion
      exchange chromatography. Haemoglobin crystals were grown by the hanging-drop
      vapour-diffusion method using PEG 3350 as the precipitant in 50 mM phosphate
      buffer pH 7.2. Data were collected using a MAR345 image-plate detector system.
      The crystals of ostrich haemoglobin diffracted to 2.2 A resolution. They belonged
      to the orthorhombic space group P2(1)2(1)2(1) with one whole biological molecule
      in the asymmetric unit; the unit-cell parameters were a = 80.93, b = 81.68, c =
      102.05 A.

PMID- 19574639
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      FeoB G domain from Methanococcus jannaschii.
AB  - The transmembrane protein FeoB plays a key role in ferrous iron acquisition in
      prokaryotes. The N-terminal domain of FeoB from Methanococcus jannaschii was
      overproduced, purified to homogeneity and crystallized in the presence of GTP and
      magnesium. The native protein crystallized in a tetragonal space group and the
      crystals diffracted to beyond 2.2 A resolution, with unit-cell parameters a = b =
      84.77, c = 137.90 A. The Matthews coefficient and the solvent content were
      estimated to be 2.65 A(3) Da(-1) and 53.64%, respectively, which corresponds to
      the presence of two molecules per asymmetric unit. To obtain initial phases,
      selenomethionyl-substituted protein was overproduced, purified and crystallized.

PMID- 19574640
TI  - Crystallization and preliminary X-ray diffraction studies of the tetramerization
      domain derived from the human potassium channel Kv1.3.
AB  - The tetramerization domain (T1 domain) derived from the voltage-dependent
      potassium channel Kv1.3 of Homo sapiens was recombinantly expressed in
      Escherichia coli and purified. The crystals were first grown in an NMR tube in
      150 mM potassium phosphate pH 6.5 in the absence of additional precipitants. The
      crystals showed I4 symmetry characteristic of the naturally occurring tetrameric
      assembly of the single subunits. A complete native data set was collected to 1.2
      A resolution at 100 K using synchrotron radiation.

PMID- 19574641
TI  - Crystallization and preliminary crystallographic studies of the single-chain
      variable fragment of antibody chA21 in complex with an N-terminal fragment of
      ErbB2.
AB  - ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes
      abnormality and disorder in cell signalling and leads to cell transformation.
      Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically
      inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was
      developed. Here, an antibody-antigen complex consisting of the single-chain
      variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1-192,
      named EP I) of the ErbB2 extracellular domain was crystallized using the sitting
      drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45
      A resolution from a single flash-cooled crystal; the crystal belonged to space
      group P2(1)2(1)2(1).

PMID- 19574642
TI  - Crystallization and preliminary X-ray diffraction studies of AsaP1_E294A and
      AsaP1_E294Q, two inactive mutants of the toxic zinc metallopeptidase AsaP1 from
      Aeromonas salmonicida subsp. achromogenes.
AB  - Two mutants of the toxic extracellular zinc endopeptidase AsaP1 (AsaP1_E294Q and
      AsaP1_E294A) of Aeromonas salmonicida subsp. achromogenes were expressed in
      Escherichia coli and crystallized by the vapour-diffusion method. Crystals were
      obtained using several precipitants and different protein concentrations. Protein
      crystals were found in a monoclinic (C2) as well as an orthorhombic
      (P2(1)2(1)2(1)) space group. The crystals belonging to the monoclinic space group
      C2 had unit-cell parameters a = 103.4, b = 70.9, c = 54.9 A, beta = 109.3 degrees
      for AsaP1_E294A, and a = 98.5, b = 74.5, c = 54.7 A, beta = 112.4 degrees for
      AsaP1_E294Q. The unit-cell parameters of the orthorhombic crystal obtained for
      AsaP1_E294A were a = 57.9, b = 60.2, c = 183.6 A. The crystals of the two
      different mutants diffracted X-rays beyond 2.0 A resolution.

PMID- 19574643
TI  - Crystallization and preliminary X-ray characterization of a glycerol
      dehydrogenase from the human pathogen Salmonella enterica serovar Typhimurium.
AB  - Glycerol dehydrogenase (GldA) encoded by the STM4108 gene (gldA) has been related
      to the synthesis of HilA, a major transcriptional regulator that is responsible
      for the expression of invasion genes in the human pathogen Salmonella enterica
      serovar Typhimurium. Single colourless crystals were obtained from a recombinant
      preparation of GldA overexpressed in Escherichia coli. They belonged to space
      group P222(1), with unit-cell parameters a = 127.0, b = 160.1, c = 665.2 A. The
      crystals contained a very large number of molecules in the asymmetric unit,
      probably 30-35. Diffraction data were collected to 3.5 A resolution using
      synchrotron radiation at the European Synchrotron Radiation Facility.

PMID- 19574644
TI  - Expression, purification, crystallization and preliminary X-ray studies of Vibrio
      cholerae pseudopilin EpsH.
AB  - EpsH is a minor pseudopilin protein of the Vibrio cholerae type II secretion
      system. A truncated form of EpsH with a C-terminal noncleavable His tag was
      constructed and expressed in Escherichia coli, purified and crystallized by
      sitting-drop vapor diffusion. A complete data set was collected to 1.71 A
      resolution. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell
      parameters a = 53.39, b = 71.11, c = 84.64 A. There were two protein molecules in
      the asymmetric unit, which gave a Matthews coefficient V(M) of 2.1 A(3) Da(-1),
      corresponding to 41.5% solvent content.

PMID- 19574645
TI  - Production, purification, crystallization and preliminary X-ray diffraction
      analysis of the HIV-2-neutralizing V3 loop-specific Fab fragment 7C8.
AB  - 7C8 is a mouse monoclonal antibody that is specific for the third hypervariable
      loop (V3 loop) of the human immunodeficiency virus type 2 (HIV-2) associated
      protein gp125. Fab fragments of 7C8 effectively neutralize HIV-2. 7C8 was
      expressed and purified from a hybridoma cell line in order to establish the
      molecular basis underlying the specificity of the 7C8 antibody for the V3 loop as
      well as the specific role of the elongated third complementarity-determining
      region of the heavy chain (CDRH3). The antibody was digested with papain and Fab
      fragments were purified using size-exclusion chromatography. Hanging-drop vapour
      diffusion crystallization techniques were employed and the protein was
      crystallized in 50 mM ammonium sulfate, 100 mM Tris-HCl pH 8.5, 25%(w/v) PEG 8000
      and 2.5%(w/v) PEG 400 at 275 K. The analysed crystals belonged to the
      rhombohedral space group P3(2)21, with unit-cell parameters a = b = 100.1, c =
      196.8 A, and diffracted to 2.7 A resolution.

PMID- 19574646
TI  - Protein preparation, crystallization and preliminary crystallographic studies of
      Bacillus subtilis glycinamide ribonucleotide transformylase.
AB  - Glycinamide ribonucleotide transformylase (GART) catalyzes the transfer of a
      formyl group from formyl tetrahydrofolate (FTHF) to glycinamide ribonucleotide
      (GAR), which is an essential step in the de novo synthesis pathway of purines. In
      Bacillus subtilis, GART is encoded by the gene purN. In order to study the
      structure and function of B. subtilis GART, the purN gene was amplified, cloned
      into an expression vector and expressed in soluble form in Escherichia coli. The
      protein was purified to homogeneity and crystals suitable for X-ray data
      collection were obtained. These crystals diffracted to 2.5 A resolution and
      belonged to space group P3(1)21, with unit-cell parameters a = b = 95.5, c = 64.0
      A.

PMID- 19574647
TI  - A crystallizable form of the Streptococcus gordonii surface antigen SspB C-domain
      obtained by limited proteolysis.
AB  - SspB is a 1500-residue adhesin expressed on the surface of the oral bacterium
      Streptococcus gordonii. Its interaction with other bacteria and host cells
      initiates the development of dental plaque. The full-length C-terminal domain of
      SspB was cloned, overexpressed in Escherichia coli and purified. However, the
      protein could not be crystallized. Limited proteolysis of the full-length C
      domain identified a core fragment. The proteolysis product was cloned, expressed
      and purified. The protein was crystallized using the hanging-drop vapour
      diffusion method. X-ray data were collected and processed to a maximum resolution
      of 2.1 A with 96.4% completeness. The crystals belonged to space group P2(1),
      with one molecule in the asymmetric unit, a solvent content of 33.7% and a
      corresponding Matthews coefficient of 1.85 A(3) Da(-1).

PMID- 19574648
TI  - Production, purification and preliminary X-ray crystallographic studies of adeno
      associated virus serotype 9.
AB  - Adeno-associated virus (AAV) serotype 9, which is under development for gene
      delivery applications, shows significantly enhanced capsid-associated
      transduction efficiency in muscle compared with other AAV serotypes. With the aim
      of characterizing the structural determinants of this property, the purification,
      crystallization and preliminary X-ray crystallographic analyses of the AAV9 viral
      capsid are reported. The crystals diffracted X-rays to 2.8 A resolution using
      synchrotron radiation and belonged to the trigonal space group P3(2), with unit
      cell parameters a = b = 251.0, c = 640.0 A. There are three complete viral
      capsids in the crystal unit cell. The orientation and position of the asymmetric
      unit capsid have been determined by molecular-replacement methods and structure
      determination is in progress.

PMID- 19574650
TI  - Preliminary structural characterization of human SOUL, a haem-binding protein.
AB  - Human SOUL (hSOUL) is a 23 kDa haem-binding protein that was first identified as
      the PP(23) protein isolated from human full-term placentas. Here, the
      overexpression, purification and crystallization of hSOUL are reported. The
      crystals belonged to space group P6(4)22, with unit-cell parameters a = b = 145,
      c = 60 A and one protein molecule in the asymmetric unit. X-ray diffraction data
      were collected to 3.5 A resolution at the ESRF. A preliminary model of the three
      dimensional structure of hSOUL was obtained by molecular replacement using the
      structures of murine p22HBP (PDB codes 2gov and 2hva), obtained by solution NMR,
      as search models.

PMID- 19574649
TI  - Preliminary crystallographic studies of the regulatory domain of response
      regulator YycF from an essential two-component signal transduction system.
AB  - YycGF is a crucial signal transduction system for the regulation of cell-wall
      metabolism in low-G+C Gram-positive bacteria, which include many important human
      pathogens. The response regulator YycF receives signals from its cognate
      histidine kinase YycG through a phosphotransfer reaction and elicits responses
      through regulation of gene expression. The N-terminal regulatory domain of YycF
      from Bacillus subtilis was overproduced and purified. The protein was
      crystallized and X-ray data were collected to 1.95 A resolution with a
      completeness of 97.7% and an overall R(merge) of 7.7%. The crystals belonged to
      space group P3(1)21, with unit-cell parameters a = b = 59.50, c = 79.06 A.

PMID- 19574651
TI  - Crystallization and preliminary X-ray crystallographic studies of DesR, a
      thermosensing response regulator in a two-component signalling system from
      Streptococcus pneumoniae.
AB  - The response regulator DesR, which activates the transcription of the des gene by
      binding to a regulatory region, is essential for controlling the fluidity of
      membrane phospholipids. DesR from Streptococcus pneumoniae was overexpressed in
      Escherichia coli. The protein was purified and crystallized for structural
      analysis. Diffraction data were collected to 1.7 A resolution using synchrotron
      radiation and the crystals belonged to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 46.91, b = 71.38, c = 117.73 A.
      Assuming the presence of a dimer in the asymmetric unit, this corresponds to a
      V(M) of 2.21 A(3) Da(-1).

PMID- 19574652
TI  - Crystallization and crystallographic analysis of the apo form of the orange
      protein (ORP) from Desulfovibrio gigas.
AB  - The orange-coloured protein (ORP) from Desulfovibrio gigas is a 12 kDa protein
      that contains a novel mixed-metal sulfide cluster of the type
      [S(2)MoS(2)CuS(2)MoS(2)]. Diffracting crystals of the apo form of ORP have been
      obtained. Data have been collected for the apo form of ORP to 2.25 A resolution
      in-house and to beyond 2.0 A resolution at ESRF, Grenoble. The crystals belonged
      to a trigonal space group, with unit-cell parameters a = 43, b = 43, c = 106 A.

PMID- 19574653
TI  - Crystallization and initial crystallographic analysis of phosphoglucosamine
      mutase from Bacillus anthracis.
AB  - The enzyme phosphoglucosamine mutase catalyzes the conversion of glucosamine 6
      phosphate to glucosamine 1-phosphate, an early step in the formation of the
      nucleotide sugar UDP-N-acetylglucosamine, which is involved in peptidoglycan
      biosynthesis. These enzymes are part of the large alpha-D-phosphohexomutase
      enzyme superfamily, but no proteins from the phosphoglucosamine mutase subgroup
      have been structurally characterized to date. Here, the crystallization of
      phosphoglucosamine mutase from Bacillus anthracis in space group P3(2)21 by
      hanging-drop vapor diffusion is reported. The crystals diffracted to 2.7 A
      resolution under cryocooling conditions. Structure determination by molecular
      replacement was successful and refinement is under way. The crystal structure of
      B. anthracis phosphoglucosamine mutase should shed light on the substrate
      specificity of these enzymes and will also serve as a template for inhibitor
      design.

PMID- 19574654
TI  - Purification, crystallization and preliminary crystallographic studies of a
      Kunitz-type proteinase inhibitor from tamarind (Tamarindus indica) seeds.
AB  - A Kunitz-type proteinase inhibitor has been purified from tamarind (Tamarindus
      indica) seeds. SDS-PAGE analysis of a purified sample showed a homogeneous band
      corresponding to a molecular weight of 21 kDa. The protein was identified as a
      Kunitz-type proteinase inhibitor based on N-terminal amino-acid sequence
      analysis. It was crystallized by the vapour-diffusion method using PEG 6000. The
      crystals belonged to the orthorhombic space group C222(1), with unit-cell
      parameters a = 37.2, b = 77.1, c = 129.1 A. Diffraction data were collected to a
      resolution of 2.7 A. Preliminary crystallographic analysis indicated the presence
      of one proteinase inhibitor molecule in the asymmetric unit, with a solvent
      content of 44%.

PMID- 19574655
TI  - Production, crystallization and preliminary crystallographic analysis of an
      exosite-containing fragment of human von Willebrand factor-cleaving proteinase
      ADAMTS13.
AB  - ADAMTS13 is a reprolysin-type metalloproteinase belonging to the ADAMTS (a
      disintegrin and metalloproteinase with thrombospondin type 1 motif) family. It
      specifically cleaves plasma von Willebrand factor (VWF) and regulates platelet
      adhesion and aggregation. ADAMTS13 is a multi-domain enzyme. In addition to the N
      terminal metalloproteinase domain, the ancillary domains, including a disintegrin
      like domain, a thrombospondin-1 type 1 repeat, a Cys-rich domain and a spacer
      domain, are required for VWF recognition and cleavage. In the present study, a
      fragment of the ADAMTS13 ancillary domains (ADAMTS13-DTCS; residues 287-685) was
      expressed using CHO Lec cells, purified and crystallized. Diffraction data sets
      were collected using the SPring-8 beamline. Two ADAMTS13-DTCS crystals with
      distinct unit-cell parameters generated data sets to 2.6 and 2.8 A resolution,
      respectively.

PMID- 19574656
TI  - Crystallization and preliminary X-ray crystallographic analysis of Escherichia
      coli CusB.
AB  - Periplasmic membrane-fusion proteins (MFPs) are an essential component of
      multidrug and metal-efflux pumps in Gram-negative bacteria. However, the
      functional structure of MFPs remains unclear. CusCFBA, the Cu(I) and Ag(I) efflux
      system in Escherichia coli, consists of the MFP CusB, the OMF CusC and the RND
      type transporter CusA. The MFP CusB bridges the inner membrane RND-type efflux
      transporter CusA and the outer membrane factor CusC and exhibits substrate-linked
      conformational changes which distinguish it from other MFP-family members. CusB
      from E. coli was overexpressed and the recombinant protein was purified using Ni
      NTA affinity, Q anion-exchange and gel-filtration chromatography. The purified
      CusB protein was crystallized using the vapour-diffusion method. A diffraction
      data set was collected to a resolution of 3.1 A at 100 K. The crystal belonged to
      space group C222.

PMID- 19574657
TI  - Rehabilitation and functional outcomes in collegiate wrestlers following a
      posterior shoulder stabilization procedure.
AB  - STUDY DESIGN: Case series. CASE DESCRIPTION: Five consecutive collegiate Division
      I wrestlers, with a mean age of 20.2 years (range, 18-22 years), were treated
      postsurgical stabilization to address posterior glenohumeral joint instability.
      All received physical therapy postoperatively, consisting of range-ofmotion,
      strengthening, and plyometrics exercises, neuromuscular re-education, and sport
      specific training. Functional outcome scores using the Penn Shoulder Score
      questionnaire were recorded at postsurgical initial evaluation and discharge.
      Isometric shoulder strength, measured with a handheld dynamometer at discharge,
      was compared with measurements made during preseason screening. OUTCOMES:
      Postsurgery, upon initial physical therapy evaluation, scores on the Penn
      Shoulder Score questionnaire ranged from 37 to 74 out of 100. All 5 wrestlers
      improved with rehabilitation such that their scores at discharge ranged from 81
      to 91 out of 100. Mean external rotation-internal rotation strength ratio for the
      involved shoulder was 73.5% (range, 55.9%-88.7%) preseason and 80.9% (range,
      70.2%-104.1%) postrehabilitation. Four patients were able to return to wrestling
      over a period of 1 season, with no episodes of reinjury to their surgically
      repaired shoulder. DISCUSSION: Current research on posterior glenohumeral
      instability is limited, due to the relatively rare diagnosis and infrequent need
      for surgical intervention. Providing a structured physical therapy program
      following this surgical procedure appeared to have assisted in a return to full
      functional activities and sports. LEVEL OF EVIDENCE: Therapy, level 4. J Orthop
      Sports Phys Ther 2009;39(7):550-559, Epub 24 February 2009.
      doi:10.2519/jospt.2009.2952.

PMID- 19574658
TI  - Physical therapy utilization of graded exposure for patients with low back pain.
AB  - SYNOPSIS: The fear-avoidance model of musculoskeletal pain suggests that elevated
      pain-related fear is a precursor to chronic low back pain. Recent prospective
      studies support the predictive validity of this model, and treatment approaches
      based on the model have also been reported in the literature. Graded
      exercise/activity is one treatment approach that has been well described in the
      literature, with reports describing physical-therapy-specific application. Graded
      exposure is another intervention with the potential to reduce pain-related fear,
      yet physical-therapy-specific application of graded exposure has not been widely
      described in the literature. The purpose of this clinical commentary was to
      provide information on the theoretical aspects of graded exposure, to briefly
      review available evidence for graded exposure, and to describe physical therapy
      application of graded exposure for 2 patients enrolled in a physical therapy
      clinical trial. LEVEL OF EVIDENCE: Therapy, level 5. J Orthop Sport Phys Ther
      2009;39(7):496-505, Epub 24 February 2009. doi:10.2519/jospt.2009.2983.

PMID- 19574659
TI  - Instrument-assisted cross-fiber massage accelerates knee ligament healing.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To investigate the effects
      of instrument-assisted cross-fiber massage (IACFM) on tissue-level healing of
      knee medial collateral ligament (MCL) injuries. BACKGROUND: Ligament injuries are
      common and significant clinical problems for which there are few established
      interventions. IACFM represents an intervention that may mediate tissue-level
      healing following ligament injury. METHODS: Bilateral knee MCL injuries were
      created in 51 rodents, while 7 rodents were maintained as ligament-intact,
      control animals. IACFM was commenced 1 week following injury and introduced 3
      sessions per week for 1 minute per session. IACFM was introduced unilaterally
      (IACFM-treated), with the contralateral, injured MCL serving as an internal
      control (nontreated). Thirty-one injured animals received 9 ACFM treatments,
      while the remaining 20 injured animals received 30 treatments. Ligament
      biomechanical properties and morphology were assessed at either 4 or 12 weeks
      postinjury. RESULTS: IACFM-treated ligaments were 43.1% stronger (P<.05), 39.7%
      stiffer (P<.01), and could absorb 57.1% more energy before failure (P<.05) than
      contralateral, injured, nontreated ligaments at 4 weeks postinjury. On
      histological and scanning electron microscopy assessment, IACFM-treated ligaments
      appeared to have improved collagen fiber bundle formation and orientation within
      the scar region than nontreated ligaments. There were minimal differences between
      IACFM-treated and contralateral, nontreated ligaments at 12 weeks postinjury,
      although IACFM-treated ligaments were 15.4% stiffer (P<.05). CONCLUSION: IACFM
      accelerated ligament healing, possibly via favorable effects on collagen
      formation and organization, but had minimal effect on the final outcome of
      healing. These findings are clinically interesting, as there are few established
      interventions for ligament injuries, and IACFM is a simple and practical therapy
      technique. J Orthop Sports Phys Ther 2009;39(7):506-514, Epub 24 February 2009.
      doi:10.2519/jospt.2009.2997.

PMID- 19574660
TI  - Medical screening and evacuation: cauda equina syndrome in a combat zone.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: Cauda equina syndrome (CES) is
      a rare, potentially devastating, disorder and is considered a true neurologic
      emergency. CES often has a rapid clinical progression, making timely recognition
      and immediate surgical referral essential. DIAGNOSIS: A 32-year-old male
      presented to a medical aid station in Iraq with a history of 4 weeks of insidious
      onset and recent worsening of low back, left buttock, and posterior left thigh
      pain. He denied symptoms distal to the knee, paresthesias, saddle anesthesia, or
      bowel and bladder function changes. At the initial examination, the patient was
      neurologically intact throughout all lumbosacral levels with negative straight
      leg raises. He also presented with severely limited lumbar flexion active range
      of motion, and reduction of symptoms occurred with repeated lumbar extension. At
      the follow-up visit, 10 days later, he reported a new, sudden onset of saddle
      anesthesia, constipation, and urinary hesitancy, with physical exam findings of
      right plantar flexion weakness, absent right ankle reflex, and decreased anal
      sphincter tone. No advanced medical imaging capabilities were available locally.
      Due to suspected CES, the patient was medically evacuated to a neurosurgeon and
      within 48 hours underwent an emergent L4-5 laminectomy/decompression. He returned
      to full military duty 18 weeks after surgery without back or lower extremity
      symptoms or neurological deficit. DISCUSSION: This case demonstrates the
      importance of continual medical screening for physical therapists throughout the
      patient management cycle. It further demonstrates the importance of immediate
      referral to surgical specialists when CES is suspected, as rapid intervention
      offers the best prognosis for recovery. LEVEL OF EVIDENCE: Differential
      diagnosis, level 4. J Orthop Sports Phys Ther 2009;39(7):541-549, Epub 24
      February 2009. doi: 10.2519/jospt.2009.2999.

PMID- 19574661
TI  - Gluteal muscle activation during common therapeutic exercises.
AB  - STUDY DESIGN: Experimental laboratory study. OBJECTIVES: To quantify and compare
      electromyographic signal amplitude of the gluteus maximus and gluteus medius
      muscles during exercises of varying difficulty to determine which exercise most
      effectively recruits these muscles. BACKGROUND: Gluteal muscle weakness has been
      proposed to be associated with lower extremity injury. Exercises to strengthen
      the gluteal muscles are frequently used in rehabilitation and injury prevention
      programs without scientific evidence regarding their ability to activate the
      targeted muscles. METHODS: Surface electromyography was used to quantify the
      activity level of the gluteal muscles in 21 healthy, physically active subjects
      while performing 12 exercises. Repeated-measures analyses of variance were used
      to compare normalized mean signal amplitude levels, expressed as a percent of a
      maximum voluntary isometric contraction (MVIC), across exercises. RESULTS:
      Significant differences in signal amplitude among exercises were noted for the
      gluteus medius (F5,90 = 7.9, P<.0001) and gluteus maximus (F5,95 = 8.1, P<.0001).
      Gluteus medius activity was significantly greater during side-lying hip abduction
      (mean +/- SD, 81% +/- 42% MVIC) compared to the 2 types of hip clam (40% +/- 38%
      MVIC, 38% +/- 29% MVIC), lunges (48% +/- 21% MVIC), and hop (48% +/- 25% MVIC)
      exercises. The single-limb squat and single-limb deadlift activated the gluteus
      medius (single-limb squat, 64% +/- 25% MVIC; single-limb deadlift, 59% +/- 25%
      MVIC) and maximus (single-limb squat, 59% +/- 27% MVIC; single-limb deadlift, 59%
      +/- 28% MVIC) similarly. The gluteus maximus activation during the single-limb
      squat and single-limb deadlift was significantly greater than during the lateral
      band walk (27% +/- 16% MVIC), hip clam (34% +/- 27% MVIC), and hop (forward, 35%
      +/- 22% MVIC; transverse, 35% +/- 16% MVIC) exercises. CONCLUSION: The best
      exercise for the gluteus medius was side-lying hip abduction, while the single
      limb squat and single-limb deadlift exercises led to the greatest activation of
      the gluteus maximus. These results provide information to the clinician about
      relative activation of the gluteal muscles during specific therapeutic exercises
      that can influence exercise progression and prescription. J Orthop Sports Phys
      Ther 2009;39(7):532-540, Epub 24 February 2009. doi:10.2519/jospt.2009.2796.

PMID- 19574662
TI  - Short-term effects of cervical kinesio taping on pain and cervical range of
      motion in patients with acute whiplash injury: a randomized clinical trial.
AB  - DESIGN: Randomized clinical trial. OBJECTIVES: To determine the short-term
      effects of Kinesio Taping, applied to the cervical spine, on neck pain and
      cervical range of motion in individuals with acute whiplash-associated disorders
      (WADs). BACKGROUND: Researchers have begun to investigate the effects of Kinesio
      Taping on different musculoskeletal conditions (eg, shoulder and trunk pain).
      Considering the demonstrated short-term effectiveness of Kinesio Tape for the
      management of shoulder pain, it is suggested that Kinesio Tape may also be
      beneficial in reducing pain associated with WAD. METHODS AND MEASURES: Forty-one
      patients (21 females) were randomly assigned to 1 of 2 groups: the experimental
      group received Kinesio Taping to the cervical spine (applied with tension) and
      the placebo group received a sham Kinesio Taping application (applied without
      tension). Both neck pain (11-point numerical pain rating scale) and cervical
      range-of-motion data were collected at baseline, immediately after the Kinesio
      Tape application, and at a 24-hour follow-up by an assessor blinded to the
      treatment allocation of the patients. Mixed-model analyses of variance (ANOVAs)
      were used to examine the effects of the treatment on each outcome variable, with
      group as the between-subjects variable and time as the within-subjects variable.
      The primary analysis was the group-by-time interaction. RESULTS: The group-by
      time interaction for the 2-by-3 mixed-model ANOVA was statistically significant
      for pain as the dependent variable (F = 64.8; P<.001), indicating that patients
      receiving Kinesio Taping experienced a greater decrease in pain immediately
      postapplication and at the 24-hour follow-up (both, P<.001). The group-by-time
      interaction was also significant for all directions of cervical range of motion:
      flexion (F = 50.8; P<.001), extension (F = 50.7; P<.001), right (F = 39.5;
      P<.001) and left (F = 3.8, P<.05) lateral flexion, and right (F = 33.9, P<.001)
      and left (F = 39.5, P<.001) rotation. Patients in the experimental group obtained
      a greater improvement in range of motion than thosein the control group (all,
      P<.001). CONCLUSIONS: Patients with acute WAD receiving an application of Kinesio
      Taping, applied with proper tension, exhibited statistically significant
      improvements immediately following application of the Kinesio Tape and at a 24
      hour follow-up. However, the improvements in pain and cervical range of motion
      were small and may not be clinically meaningful. Future studies should
      investigate if Kinesio Taping provides enhanced outcomes when added to physical
      therapy interventions with proven efficacy or when applied over a longer period.
      LEVEL OF EVIDENCE: Therapy, level 1b. J Orthop Sports Phys Ther 2009;39(7):515
      521, Epub 24 February 2009. doi:10.2519/jospt.2009.3072.

PMID- 19574663
TI  - Shoe inserts alter plantar loading and function in patients with midfoot
      arthritis.
AB  - STUDY DESIGN: Experimental laboratory study supplemented by a case series.
      OBJECTIVES: (1) To assess the effect of a 4-week intervention with a full-length
      insert on functional outcomes in patients with midfoot arthritis; (2) to examine
      the effect of the custom molded three-quarter-length (3Q) and full-length (FL)
      carbon graphite insert on plantar loading in patients with midfoot arthritis.
      BACKGROUND: Given the coexistence of pain and lower-arched foot alignment in
      patients with midfoot arthritis, arch-restoring orthotic devices such as the 3Q
      insert are frequently recommended. However, patients continue to report foot pain
      despite using the 3Q insert. The FL insert has been proposed as an alternative,
      but objective data examining its efficacy are lacking. METHODS: Twenty female
      patients with midfoot arthritis participated in the study. Functional outcomes
      were assessed using the Foot Function Index-Revised (FFI-R). Plantar loading
      during walking was measured in the following conditions: shoe only, shoe with 3Q
      insert, and shoe with FL insert. Repeated-measures analyses of variance with post
      hoc analyses were used for statistical analysis. RESULTS: FL insert use for 4
      weeks resulted in a 12% improvement in total FFI-R score (mean +/- SD before,
      35.6 +/- 10.9; after, 31.1 +/- 9.8 [P = .03]). FL insert use resulted in a 20%
      reduction in medial midfoot average pressure loading (mean +/- SD, 64.8 +/- 20.4
      and 51.0 +/- 15.4 kPa, with 3Q and FL insert respectively [P = .015]) and an 8.5%
      reduction in medial midfoot contact time (mean +/- SD, 84.9% +/- 6.4% and 76.4%
      +/- 7.1% of stance, with 3Q and FL insert respectively [P<.01]), compared to the
      3Q insert. No differences in plantar loading were discerned between the shoe-only
      and FL conditions. CONCLUSION: Symptomatic improvement in patients with midfoot
      arthritis treated with a FL insert was accompanied by reduced magnitude and
      duration of loading under the medial midfoot. These preliminary outcomes suggest
      that the FL insert may be a viable alternative in the conservative management of
      patients with midfoot arthritis. LEVEL OF EVIDENCE: Therapy, level 4. J Orthop
      Sports Phys Ther 2009;39(7):522-531. doi:10.2519/jospt.2009.2900.

PMID- 19574664
TI  - Bipartite patella in a young athlete.
AB  - The patient was a 12-year-old male with a chief complaint of right anterior knee
      pain for the past 3 months. The patient was referred to physical therapy by an
      orthopaedic surgeon with a diagnosis of patellofemoral pain and bipartite
      patella. The patient was advised to avoid painful activities and a quadriceps
      strengthening program was initiated. At the time of discharge, the patient had
      normal quadriceps strength and pain-free knee range of motion. Often an
      asymptomatic and incidental finding, bipartite patella results when secondary
      ossification centers do not fuse to form a single bone. Treatment typically
      entails rest and conservative management; however, in individuals with persistent
      symptoms that are not responsive to conservative measures, surgical intervention
      may be necessary.J Orthop Sports Phys Ther 2009;39(7):560.
      doi:10.2519/jospt.2009.0407.

PMID- 19574666
TI  - Everyone is concerned about costs!

PMID- 19574667
TI  - Delayed lymphadenectomy in patients with carcinoma of penis.

PMID- 19574668
TI  - Economic cost analysis in cancer management and its relevance today.
AB  - The global cancer burden has shown a distinct shift in the last two decades and
      its financial impact can be large, even among patients living in high resource
      countries, with comprehensive health insurance policies. It is hard to imagine
      its impact on patients of developing countries where insurance policies exist
      infrequently and often cost becomes the greatest barrier in availing cancer
      treatment. It is recognized that these costs include the direct cost of disease
      treatment and care, indirect costs accrued by the patient and the family, and
      economic losses to the society as a whole. Economic cost analysis or cost
      effectiveness analysis has emerged as a basic tool in the evaluation of health
      care practices. To date, these cost data have been collected only sporadically,
      even in the most developed countries, and there is a great need for incorporating
      economic cost assessment practices in developing countries, so that patients and
      their families can access the care adequately. The current review has been done
      using PubMed and MEDLINE search with keywords like cancer, cost-analysis, cost
      effectiveness, economic burden, medical cost, etc.

PMID- 19574669
TI  - Screening for human papillomavirus: is urine useful?
AB  - Persistent infection with high-risk Human papillomavirus (hr-HPV 16, 18, 31, 33,
      and 45) is the main risk factor for developing malignant genital lesions.
      Screening methods and follow-up schedules for cervical cancer are well known. A
      golden standard to screen and monitor men does not exist yet, because HPV
      related, life threatening malignancies in men are rare. The importance of male
      HPV screening lies mainly in HPV vaccination. Young females are the target group
      for HPV, but men are considered to be the reservoir for HPV and to have a role in
      the perpetuation of the infection in the general population. We looked at the
      usefulness of urine as a tool for HPV screening. Pubmed was searched with the
      words ''HPV'', ''Urine,'' and ''HPV-DNA''. The chance of finding HPV-DNA in urine
      is higher in men with lesions in the urethra than outside the urethra, and in
      women with abnormal cervical cytology. In general, the results of testing urine
      for HPV-DNA are better for women than for men, probably because of the anatomical
      position of the urethra to the vagina, vulva, and cervix. In both genders, urine
      HPV prevalence is higher in HIV pos patients and in high-risk populations. Urine,
      to screen asymptomatic low-risk-profile (wo)men seems less useful because their
      urine samples are often inadequate. If urine proves to be the best medium to
      screen, a low-risk population remains controversial.

PMID- 19574670
TI  - Clinical significance of matrix metalloproteinase 2 and 9 in breast cancer.
AB  - BACKGROUND: Invasion and metastasis are the most strenuous problems in the
      management of breast cancer. These events require diverse proteolytic enzymes,
      among which MMP-2 and MMP-9 play a significant role in degradation of type IV
      collagen, the major component of the basement membrane. Therefore, the major
      objective of the study is to evaluate the clinical usefulness of MMP-2 and MMP-9
      with respect to malignant tumor growth, invasion, and metastasis in breast
      cancer. MATERIALS AND METHODS: Gelatin zymography was performed on 157 tissue
      extracts of malignant and adjacent normal breast tissues as well as negative and
      positive lymph nodes from 49 breast cancer patients. Statistical analysis was
      carried out using SPSS statistical software (version 10). RESULTS: ProMMP-2
      levels were significantly higher in adjacent normal tissues. Active MMP-2 and MMP
      9 levels were higher in malignant breast tissues. Activation ratios of MMP-2 and
      MMP-9 were significantly higher in malignant breast tissues and in patients with
      lymph node metastasis. ProMMP-2, active MMP-2, and active MMP-9 could
      significantly discriminate between malignant and adjacent normal breast tissues.
      The MMP-2 activation ratio showed significant discriminatory efficacy between
      patients with and without lymph node metastasis and significant association with
      increased risk of lymph node metastasis in node-negative patients. CONCLUSION:
      The results indicate significant clinical utility of these proteolytic enzymes in
      malignant tumor growth, invasion, and metastasis in breast cancer.

PMID- 19574671
TI  - HPV type 18 is more oncopotent than HPV16 in uterine cervical carcinogenesis
      although HPV16 is the prevalent type in Chennai, India.
AB  - CONTEXT: The highest incidence of uterine cervical cancer in India is reported in
      Chennai. The prevalence and oncopotency are to be considered for the development
      of vaccines and therapeutic agents. AIMS: The aim of the present study is to
      analyze the prevalence and oncopotency of high risk type HPV16 and 18 in cervical
      lesions. SETTINGS AND DESIGN: This study is designed with 130 study subjects for
      analysis of selected types of HPV 6/11 and 16/18, in four groups, in a course of
      three years. The Bethesda system of classification is followed for grouping the
      samples, using histopathologic examination in biopsies. MATERIALS AND METHODS:
      The biopsy samples were collected in 10% buffered formalin and were embedded in
      paraffin within 24 hours, for long-term preservation. The presence of HPV types
      were tested by PCR using type-specific primers for HPV16 and HPV18 in the DNA
      isolated from the subject's biopsies. The stages of cervical lesions were
      identified by histopathology using the Hematoxylin Eosin stain. STATISTICAL
      ANALYSIS USED: The data were subjected to statistical analysis, using the SPSS
      and INSTAT software packages for their associations and risk estimation,
      respectively. The Graph Pad Prism 2 x 2 contingency table was used for risk
      estimation and the Kruskel Wallis test was used for analysis of the associations.
      RESULTS: In the study population, the data indicated a high prevalence of HPV 16.
      However, during the course of study (1999 - 2003), four (66.6%) dysplasia cases
      with HPV 18, three (21.4%) dysplasia cases with HPV 16, and none with low-risk
      HPV6/11, turned into invasive cancer, within one year. CONCLUSIONS: The
      observation of the study implied that HPV16 had a high prevalence in uterine
      cervical cancer compared with HPV18 cases. However, the development of invasive
      cancer from precancerous lesions was more for HPV18 infected cases than for HPV16
      during the study period, which indicated the higher oncopotency of HPV type 18.

PMID- 19574672
TI  - Breast self-examination among nurses and midwives in Odemis health district in
      Turkey.
AB  - BACKGROUND: The second leading cause of death due to cancer in Turkey is breast
      cancer, which accounts for 24% of female cancers. AIMS: To determine the
      practices of nurses and midwives and their attitude toward breast self
      examination (BSE). SETTING AND DESIGN: The descriptive survey was conducted to
      determine the practices of nurses and midwives and their attitude toward BSE. It
      tried to cover the total population rather than sampling part of it. However, 15
      nurses and midwives, where there were errors detected in their data coding
      papers, and who did not accept to join the study, were excluded from the study. A
      total of 80 nurses and midwives were included in the study group. MATERIALS AND
      METHODS: This survey was carried out at the State Hospital, all Public Health
      Cabins, and Family Health Centers, in the rural area of Izmir, a city located in
      the western region of Turkey. The data was collected between 15 March and 1 April
      2004. STATISTICAL ANALYSIS: The analysis included descriptive statistics, to
      examine the association between BSE and medical history, knowledge of BSE, and
      attitude toward BSE. RESULTS: The results of the study indicated that 52% of the
      sample performed BSE. Approximately 35% of those who performed BSE reported that
      they acquired information regarding BSE during their work experience. A
      significant relationship was found between higher levels of work experience and
      BSE practice. Except for age, no significant relation was found between the
      sociodemographic factors and BSE practice. The sample showed a strong belief in
      the breast lump being the cause of breast cancer and it had a significant
      correlation with BSE practice. CONCLUSION: A positive correlation was found
      between nursing work experience and their practice alongside BSE medical
      professionals. Almost all the nurses and midwives knew how to conduct BSE, but
      did not prioritize practicing it.

PMID- 19574673
TI  - Impact of delay in inguinal lymph node dissection in patients with carcinoma of
      penis.
AB  - AIM: To study the impact of delay in inguinal lymph node dissection (LND) in
      patients with squamous cell carcinoma of the penis, who have indications for LND
      at the time of presentation. MATERIALS AND METHODS: In total, 28 patients (mean
      age 52.1 +/- 12.8 years) with squamous cell carcinoma of the penis, treated from
      January 2000 to June 2008, were retrospectively studied with regard to clinical
      presentation, time of LND, and the outcome. The patients were divided into two
      groups based on the time for LND. Group 1 patients had LND at mean of 1.7 months
      (range 0-6 months) of treatment of the primary lesion, and group 2 had LND at a
      mean of 14 months (range 7-24 months) after treatment of the primary lesion.
      STATISTICAL ANALYSIS: The statistical analysis of survival was done using the
      Kaplan-Meier method and the Log Rank test, with p < 0.05 considered to be
      statistically significant. The Mann-Whitney test and Fisher's exact test were
      used for univariate comparison. RESULTS: Twenty-three of the 28 patients had
      inguinal LND. In group 1, of 13 patients, 12 were alive, with no recurrence of
      disease at a mean follow-up of 37 months (8-84) months. In group 2, only two
      patients were alive and disease-free, at a mean follow-up of 58 months (33-84
      months). The five-year cancer-specific survival rates for early and delayed LND
      were 91 and 13%, respectively, (p = 0.007). CONCLUSIONS: When compliance with
      follow-up is suspect, patients with high grade or T stage (greater than T1) tumor
      are better treated by inguinal LND during the same hospital admission or within
      two months of primary treatment.

PMID- 19574674
TI  - Mutation pattern of K-ras gene in colorectal cancer patients of Kashmir: a
      report.
AB  - BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading malignancies
      worldwide. CRC has been reported to show geographical variation in its incidence,
      even within areas of ethnic homogeneity. The aim of this study is to identify K
      ras gene mutations in CRC patients among the Kashmiri population, and to assess
      whether they are linked with the clinicopathological parameters. MATERIALS AND
      METHODS: Paired tumor and normal tissue samples were collected from a consecutive
      series of 53 patients undergoing resective surgery for CRC. In addition blood was
      also collected from all the cases for ruling out germline mutation. RESULTS:
      Colorectal patients, 22.64% (12 of 53), presented with mutations in K-ras
      constituting 13 missense mutations out of which 11 were G-->A transition, one G-
      >C transversion, and one G-->T transversion. 61.5% percent of the mutations
      occurred in codon 12 and 38.5% in codon 13. One tumor contained missense
      mutations in both codons. K-ras mutations were significantly associated with
      advanced Dukes' stage (P < 0.05) and positive lymph node status (P < 0.05).
      Moreover Codon 12 K-ras mutations were associated with mucinous histotype (P <
      0.05). Comparison of the mutation profile with other high-risk areas reflected
      both mucinous histotype differences and similarities indicating coexposure to a
      unique set of risk factors. CONCLUSION: Mutation of the K-ras gene is one of the
      commonest genetic changes in the development of human CRC, but it occurs in a
      rather low frequency in Kashmiri population.

PMID- 19574675
TI  - Assessment of gynecologic malignancies: a multi-center study in Tehran (1995
      2005).
AB  - OBJECTIVE: The observed differences in cancer incidence are mainly due to
      different individuals and social risk factors. This study aims to demonstrate the
      characteristics of female genital malignancies according to the pathological
      records in Tehran, Iran. MATERIALS AND METHODS: In this cross-sectional study,
      all records of pathological specimens categorized as ovarian, uterine corpus or
      uterine cervix cancers from 1995 to 2005, in five teaching hospitals in Tehran,
      were studied. Age, marriage, parity, menopausal status, smoking, oral
      contraceptive usage, pathological staging, and histological grading were reviewed
      by a trained general practitioner. SPSS 14 was used for statistical analysis.
      RESULT: Mean age (SD) at the time of diagnosis was 50 (15). Fifty-nine percent of
      ovarian, 33.9 and 47.7% of uterine corpus and uterine cervix malignant patients
      were premenopausal. About 90% of all were nonsmokers and 82.7% were multiparae.
      Various types of gynecologic malignancies included ovarian (55.5%), uterine
      corpus (24.9%), and uterine cervical cancers (19.6%) were diagnosed. In tumors of
      the uterine corpus and uterus cervix, the most frequent stage of diagnosis was
      stage IIA. CONCLUSION: Ovarian cancer was the most frequently occurring
      gynecologic tumor. Although distribution of age in ovarian cancer was similar to
      that mentioned in the literature, occurrence of the cancer was more frequent in
      the premenopausal state.

PMID- 19574676
TI  - Gnathic osteosarcomas: a 10-year multi-center demographic study.
AB  - BACKGROUND: Osteosarcomas (OS) of the jaws are uncommon lesions representing 6-8%
      of skeletal OS. We assessed the characteristics, demographics, prevalence
      clinical and histopathological findings and distribution of gnathic OS relative
      to non-gnathic OS in four major treatment centers. MATERIALS AND METHODS: This
      study assessed 13 gnathic OS patients of 98 OS patients from four major referral
      centers during 1996-2007. The age distribution, gender, involved site, clinical
      findings, signs, symptoms, grade and sub-types were assessed. Hematoxylin-eosin,
      Picrosirius red, Ponceau trichrome, Masson trichrome and osteoid staining methods
      were used. RESULTS: Of the 98 OS lesions, 85 (86.8%) involved the skeleton, the
      youngest patient was 6 and the oldest 60 years old; 13 lesions (13.2%) involved
      the jaws (seven mandibular and six maxillary) and the youngest and oldest
      patients were 15 and 50 years-old, respectively. Non-gnathic OS was more
      prevalent between the ages of 11 and 20 years (avg. 15 years) and was common in
      the distal femur and proximal tibia, presenting most frequently with pain and
      swelling. OS of the jaws, however, presented more than 10 years later than non
      gnathic OS, being more prevalent between the ages of 20 and 30 years (avg. 27
      years). OS of the jaws most frequently involved the mandibular body and the
      posterior maxillary alveolar ridge, presenting frequently with pain, swelling and
      loosening of teeth. Two patients with gnathic OS died during the 10-year follow
      up period (15.3%). CONCLUSION: Prevalence of OS of the jaws was about twice as
      high as that reported in other studies and presented later than non-gnathic
      cases. Pain and swelling were common signs and symptoms in this disease. The
      mixed sub-type was the most common sub-type of gnathic OS.

PMID- 19574677
TI  - Benign tumors and tumor-like lesions of the calcaneum: a study of 12 cases.
AB  - Benign tumors of the calcaneum are rare. Cystic lesions such as simple bone cysts
      and aneurysmal bone cysts are commonly seen. AIMS AND OBJECTIVES: To evaluate
      tumors of the calcaneum, which were seen over a 12-year period. MATERIALS AND
      METHODS: We analyzed noninfectious, noninflammatory, benign lesions of the
      calcaneum seen in the Orthopedic Out Patient Department from 1991 to 2003. Twelve
      such tumors were encountered. There were 11 males and one female and their ages
      varied from 18 to 53 years with a median of 31. Data was collected from the
      histopathology reports, radiographs, and inpatient and outpatient records. One of
      the coauthors reviewed the histopathologic findings of all the tumors. RESULTS:
      Twelve benign lesions were seen in 12 patients. In our series, cysts
      predominated, with three aneurysmal bone cysts and five simple bone cysts. The
      other benign tumors were: one fibrous dysplasia, one vascular hamartoma, one
      osteoblastoma, and one chondromyxoid fibroma. The bone cysts were treated by
      curettage, with or without bone grafting, except for one large aneurysmal bone
      cyst, which was treated by excision of the calcaneum. The postoperative function
      in this patient was good, with modified footwear. CONCLUSION: The calcaneum is an
      uncommon site for most bone tumors, and in our series, bone cysts were the most
      common benign lesions. Curettage and bone grafting or the use of bone substitutes
      can be effectively used in the treatment of symptomatic bone cysts of the
      calcaneum.

PMID- 19574678
TI  - Positron emission tomography / computerized tomography evaluation of primary
      Hodgkin's disease of liver.
AB  - Occurrence of primary Hodgkin's lymphoma (PHL) of the liver is extremely rare. We
      report on a case of a 60-year-old male who presented with liver mass and B
      symptomatology. Hepatoma or hepatic metastasis from a gastrointestinal primary
      was initially suspected. Tumor markers like AFP, CEA, Total PSA, and CA-19.9 were
      within normal limits. Positron Emission Tomography / Computerized Tomography
      (PET/CT) revealed a large hepatic lesion and a nodal mass in the porta hepatis. A
      liver biopsy was consistent with Hodgkin's lymphoma. There was complete
      regression of the hepatic lesion and evidence of shrinkage of the nodal mass
      following four cycles of chemotherapy. 18F Fluro -de-oxy Glucose (FDG) PET / CT
      in this case helped in establishing a primary hepatic lymphoma by demonstrating
      the absence of pathologically hypermetabolic foci in any other nodes or organs.
      PET / CT scan is a useful adjunct to conventional imaging and histopathology, not
      only to establish the initial diagnosis, but also to monitor treatment response
      in PHL.

PMID- 19574679
TI  - Anaplastic large cell lymphoma presenting as liver abscess and portal vein
      thrombosis.

PMID- 19574680
TI  - A case of leiomyosarcoma of kidney clinically and radiologically misdiagnosed as
      renal cell carcinoma.

PMID- 19574681
TI  - Marine life: new hope for cancer drugs.

PMID- 19574682
TI  - Infiltrating duct carcinoma within a fibroadenoma.

PMID- 19574683
TI  - Enterocolic fistula associated with a gastrointestinal stromal tumor.

PMID- 19574684
TI  - Virilizing adrenal carcinoma with inferior vena cava thrombus.

PMID- 19574685
TI  - Zoledronic acid induced osteonecrosis of tibia and femur.

PMID- 19574686
TI  - Testicular tuberculosis masquerading as testicular tumor.

PMID- 19574687
TI  - Lack of awareness about breast cancer and its screening in developing countries.

PMID- 19574688
TI  - Alpha-fetoprotein production by non-hepatocellular carcinoma, malignant liver
      tumor.

PMID- 19574689
TI  - Authorship criteria and the role of reviewers and the editor.

PMID- 19574690
TI  - Adverse drug reactions.

PMID- 19574691
TI  - Off with the label and on the Avastin bandwagon: why now and how far?

PMID- 19574693
TI  - Functional and anatomical outcomes after primary lens-sparing pars plana
      vitrectomy for Stage 4 retinopathy of prematurity.
AB  - BACKGROUND: While lens-sacrificing vitrectomy is the standard approach to manage
      Stage 5 retinopathy of prematurity (ROP), scleral buckling has been used to
      manage some cases of Stage 4. Lens-sparing vitrectomy was popularized by Maguire
      and Trese in selected cases of Stage 4 disease. PURPOSE: To assess the functional
      and visual outcomes after primary lens-sparing pars plana vitrectomy for Stage 4
      ROP. MATERIALS AND METHODS: In a retrospective, interventional, consecutive case
      series, the records of 39 eyes of 31 patients presenting with Stage 4 retinal
      detachment secondary to ROP who underwent primary two or three-port lens-sparing
      vitrectomy from January 2000 to October 2006 were evaluated. The outcomes studied
      at the final follow-up visit were the retinal status, lens and medial clarity and
      visual acuity . Favorable anatomical outcome was defined as the retinal
      reattachment of the posterior pole at two months after the surgery; and favorable
      functional outcome was defined as a central, steady and maintained fixation, with
      the child following light. RESULTS: At mean follow-up of 15 months, 74% of the
      eyes had a favorable anatomical outcome with single procedure. The visual status
      was favorable in 63% . The lens remained clear in all the eyes at the last follow
      up, and the media clarity was maintained in 87%. Intraoperative complications
      included vitreous hemorrhage, pre-retinal hemorrhage and retinal break formation.
      CONCLUSIONS: Lens-sparing vitrectomy helps to achieve a favorable anatomical and
      functional outcome in selected cases of Stage 4 ROP.

PMID- 19574692
TI  - Current concepts in the pathophysiology of glaucoma.
AB  - Glaucoma, the second leading cause of blindness, is characterized by changes in
      the optic disc and visual field defects. The elevated intraocular pressure was
      considered the prime factor responsible for the glaucomatous optic neuropathy
      involving death of retinal ganglion cells and their axons. Extensive
      investigations into the pathophysiology of glaucoma now reveal the role of
      multiple factors in the development of retinal ganglion cell death. A better
      understanding of the pathophysiological mechanisms involved in the onset and
      progression of glaucomatous optic neuropathy is crucial in the development of
      better therapeutic options. This review is an effort to summarize the current
      concepts in the pathophysiology of glaucoma so that newer therapeutic targets can
      be recognized. The literature available in the National Medical Library and
      online Pubmed search engine was used for literature review.

PMID- 19574694
TI  - Review of epidemiological features, microbiological diagnosis and treatment
      outcome of microbial keratitis: experience of over a decade.
AB  - PURPOSE: To review the epidemiological characteristics, microbiological profile,
      and treatment outcome of patients with suspected microbial keratitis. MATERIALS
      AND METHODS: Retrospective analysis of a non-comparative series from the database
      was done. All the patients presenting with corneal stromal infiltrate underwent
      standard microbiologic evaluation of their corneal scrapings, and smear and
      culture-guided antimicrobial therapy. RESULTS: Out of 5897 suspected cases of
      microbial keratitis 3563 (60.4%) were culture-proven (bacterial--1849, 51.9%;
      fungal--1360, 38.2%; Acanthamoeba--86, 2.4%; mixed--268, 7.5%). Patients with
      agriculture-based activities were at 1.33 times (CI 1.16-1.51) greater risk of
      developing microbial keratitis and patients with ocular trauma were 5.33 times
      (CI 6.41-6.44) more likely to develop microbial keratitis. Potassium hydroxide
      with calcofluor white was most sensitive for detecting fungi (90.6%) and
      Acanthamoeba (84.0%) in corneal scrapings, however, Gram stain had a low
      sensitivity of 56.6% in detection of bacteria. Majority of the bacterial
      infections were caused by Staphylococcus epidermidis (42.3%) and Fusarium species
      (36.6%) was the leading cause of fungal infections. A significantly larger number
      of patients (691/1360, 50.8%) with fungal keratitis required surgical
      intervention compared to bacterial (799/1849, 43.2%) and Acanthamoeba (15/86,
      17.4%) keratitis. Corneal healed scar was achieved in 75.5%, 64.8%, and 90.0% of
      patients with bacterial, fungal, and Acanthamoeba keratitis respectively.
      CONCLUSIONS: While diagnostic and treatment modalities are well in place the
      final outcome is suboptimal in fungal keratitis. With more effective treatment
      available for bacterial and Acanthamoeba keratitis, the treatment of fungal
      keratitis is truly a challenge.

PMID- 19574695
TI  - Evaluation of central, steady, maintained fixation grading for predicting inter
      eye visual acuity difference to diagnose and treat amblyopia in strabismic
      patients.
AB  - BACKGROUND: Diagnosis of amblyopia in preverbal strabismic patients is frequently
      made by binocular fixation preference (BFP) testing. The reports on reliability
      of BFP are equivocal. This study evaluated the reliability of BFP testing in
      patients with horizontal strabismus. MATERIALS AND METHODS: This prospective
      observational study included patients with manifest, horizontal, comitant
      deviation> 10 prism diopter (PD). Inter-eye acuity difference (IEAD) was
      calculated by converting Snellen visual acuity to logMAR and was compared with
      BFP testing. The fixation behavior of the non-preferred eye was evaluated by a
      single investigator as central or uncentral, steady or unsteady and maintained or
      unmaintained. Amblyopia was defined as the IEAD of> 0.2 logMAR. RESULTS: Of total
      61 patients 36 were females and 36 had convergent squint, mean age 9.8 years. The
      correlation of BFP testing with IEAD was good for esotropia and exotropia. The
      sensitivity, specificity, positive and negative predictive value of central,
      steady, maintained (CSM) grading was 93%, 78%, 79%, and 93% respectively.
      Sensitivity and negative predictive values were higher in children aged four to
      nine years and anisometropia> 1 diopter. The correlation between IEAD and lower
      grades of BFP testing was poor. CONCLUSIONS: CSM grading for BFP testing is
      useful for the detection of strabismic amblyopia but not useful to differentiate
      the depth of the amblyopia.

PMID- 19574696
TI  - Comparison of psychosocial and emotional consequences of childhood strabismus on
      the families from rural and urban India.
AB  - PURPOSE: To compare the psychosocial consequences of horizontal comitant
      strabismus in children between the families of urban and rural India. MATERIALS
      AND METHODS: In this cohort study, an eight-question quality-of-life instrument
      was administered by trained staff to the guardians of strabismic children from
      rural and urban areas by a live interview. RESULTS: This study included 93
      strabismic-children aged 4-16 years of which 52 were females. Forty-one had
      esodeviation and 52 had exodeviation. Seventy per cent parents were extremely
      distressed due to squint, 65% were extremely distressed due to people's remarks,
      65% were extremely worried, 55% children were extremely distressed due to
      people's remarks, 57% children were severely ostracized, 38% had severe
      difficulty in communication and 50% had difficulty to cope; 64% parents were not
      advised a corrective surgery. The difference between families from rural and
      urban areas, or whether a male child was affected or a female child or for an
      esodeviation or an exodeviation was statistically not significant. The
      questionnaire had a good internal consistency (Cronbach's Alpha = 0.71).
      CONCLUSIONS: There was a significant negative psychosocial and emotional impact
      of childhood strabismus that was not affected by the rural or urban location of
      the family or the gender of the strabismic child or type of the deviation. The
      quality-of-life instrument can be used as part of the clinical examination for
      strabismic children.

PMID- 19574697
TI  - Tear ascorbic acid levels and the total antioxidant status in contact lens
      wearers: a pilot study.
AB  - AIMS: The tear ascorbate owing to its high concentration, functions as an
      effective antioxidant against the oxidative damage of cornea. Contact lens
      wearers (CLW) are prone to oxidative stress due to the lens-induced hypoxic
      conditions. A pilot study was done to compare the tear ascorbic acid level and
      the total antioxidant capacity give as in normal and CLW. MATERIALS AND METHODS:
      In this study 21 CLW (Mean age 23 +/- 3 years ; M-2, F-19), who were daily wear
      users, with duration of wear not more than four years, along with age-matched 28
      controls (Mean age 28 +/- 3 ; M-15, F-13) were recruited in the study for
      collection of reflex tears using Schirmer's strip. Ascorbic acid in tears was
      determined using high-performance liquid chromatography (HPLC), total antioxidant
      capacity (TAC) and total protein assay by spectrophotometric analysis. RESULTS:
      CLW showed no significant change in the tear ascorbic acid levels (0.4 +/- 0.26
      mM) compared to the control subjects (0.61 +/- 0.59 mM). The amount of ascorbic
      acid in tears did not correlate with the TAC or the total protein of the tears.
      The mean TAC in CLW was 0.69 +/- 0.16 mM, with a total protein of 1.35 +/- 0.46
      mg/ml while in controls it was 0.7 +/- 0.18 mM and 1.21 +/- 0.47 mg/ml
      respectively. CONCLUSIONS: Soft contact lens wear did not show any significant
      change in tear ascorbic acid, TAC and total protein levels compared to controls.

PMID- 19574698
TI  - Diabetic retinopathy, visual impairment and ocular status among patients with
      diabetes mellitus in Yemen: a hospital-based study.
AB  - BACKGROUND: We present a series of patients with diabetes mellitus (DM) who
      attended an eye hospital in Sana, Yemen during 2004. AIM: To determine the
      magnitude and risk factors of diabetic retinopathy (DR). DESIGN: Cross-sectional
      study. MATERIALS AND METHODS: Ophthalmologists assessed vision, ocular pressure,
      ocular media and posterior segment to note ocular manifestations among patients
      with DM. DR was graded by using bio-microscope and Volk lens. The prevalence and
      95% confidence interval of ocular complications of DM were calculated. Risk
      factors of DR like age, sex, duration of diabetes and hypertension were
      evaluated. STATISTICAL ANALYSIS: Univariate and multivariate analysis. RESULTS:
      Our series comprised 350 patients suffering from DM. The duration of diabetes was
      > or =15 years in 101 (29%) patients. Physician was treating 108 DM patients with
      insulin. The prevalence of DR was 55% (95% CI 49.6-60.1). The proportions of
      background diabetic retinopathy (BDR), preproliferative diabetic retinopathy
      (PPDR), proliferative diabetic retinopathy (PDR) and diabetic macular edema were
      20%, 13%, 17% and 22% respectively. The prevalence of blindness among DM patients
      was 16%. The prevalence of cataract and glaucoma was 34.3% and 8.6%. Duration of
      DM was the predictor of DR. One-fifth of the patients had sight-threatening DR
      and needed laser treatment. CONCLUSIONS: DR was of public health magnitude among
      our patients. An organized approach is recommended to address DR in the study
      area.

PMID- 19574699
TI  - Vitamin A-first dose supplement coverage evaluation amongst children aged 12-23
      months residing in slums of Delhi, India.
AB  - OBJECTIVE: To determine vitamin A-first dose supplement coverage in children aged
      12-23 months and to find out its correlates with selected variables. MATERIALS
      AND METHODS: The 30-cluster sampling technique based on probability proportional
      to size advocated by the World Health Organization was used to assess vitamin A
      first dose supplement amongst 210 children in the age group of 12-23 months
      residing in slums of a randomly selected municipal zone of Delhi during October
      to November 2005. RESULTS: Only 79 (37.6%) children out of 210 had received
      vitamin A-first dose supplement. Further analysis of 79 children was carried out
      with regard to selected variables like religion, gender, birth order, place of
      birth, immunization status and literacy of mother. These analyses showed that 71
      (89.9%) were Hindu and eight (10.1%) were non-Hindu ( P = 0.04). Nearly 44
      (55.7%) males and 35 (44.3%) females had received vitamin A ( P = 0.74). The
      proportion of children born in a health institution who received first dose (57%)
      of vitamin A supplementation was significantly higher than of those who were born
      at home (43%) ( P 0.001). Similarly, higher proportion of children with birth
      order-one (48.1%) in comparison to birth order-three or above (26.6%) received
      vitamin A ( P 0.001). Thirty children though fully immunized for vaccine
      preventable disease up to the age-of-one year had not received vitamin A-first
      dose supplement, suggesting that an opportunity had been missed. The association
      between receipt of vitamin A by the child and literacy status of mother was found
      to be significant ( P 0.001). CONCLUSION: The study reflects low coverage of
      Vitamin A supplement.

PMID- 19574701
TI  - Successful management of presumed Candida endogenous endophthalmitis with oral
      voriconazole.
AB  - Endogenous fungal endophthalmitis is most commonly caused by Candida species and
      usually occurs in patients with chronic diseases such as diabetes mellitus and
      renal insufficiency. Voriconazole, a broad-spectrum triazole antifungal agent,
      attains therapeutically significant concentrations in the vitreous cavity after
      systemic administration. We report, the successful management of presumed
      endogenous Candida endophthalmitis in a patient with multiple diseases and
      unstable systemic status with oral voriconazole. Though fungal endophthalmitis
      has been successfully treated with a combination of intravenous and intravitreal
      voriconazole, to the best of our knowledge this is the first report in ophthalmic
      literature (Medline Search) on the treatment of fungal endophthalmitis with only
      the oral route of administration of voriconazole.

PMID- 19574700
TI  - Vertical lid split approach for optic nerve sheath decompression.
AB  - We describe a vertical lid split orbitotomy approach to perform optic nerve
      sheath fenestration which was done in a patient with idiopathic intracranial
      hypertension. A vertical lid split incision was used to enter the superomedial
      orbit and approach the optic nerve sheath. This approach resulted in a successful
      nerve sheath fenestration, with improvement in the patient's symptoms. The
      vertical lid split incision provides access to the optic nerve sheath with
      minimal morbidity and may be an option for optic nerve sheath decompression.

PMID- 19574702
TI  - Scleral ulceration after vitreoretinal surgery.
AB  - Scleral ulceration after ocular surgery is a rare but serious complication.
      Determination of the underlying systemic and local causes is critical for
      treatment. An unusual case of ischemic scleral ulceration after vitreoretinal
      surgery in a diabetic patient is reported. Patient was successfully treated with
      a pedicle conjunctival graft.

PMID- 19574704
TI  - Aniridia associated with congenital aphakia and secondary glaucoma.
AB  - We report a case of aniridia associated with congenital aphakia and secondary
      glaucoma. A 35-year-old male presented with aniridia, congenital aphakia and
      secondary glaucoma in both eyes. After an unsuccessful medical management, he
      underwent trabeculectomy with mitomycin C and anterior vitrectomy under local
      anesthesia in his left eye. Postoperatively, at the end of six months,
      intraocular pressure (IOP) in his left eye was controlled without medications.
      This case highlights the rare association of aniridia with congenital aphakia and
      secondary glaucoma.

PMID- 19574703
TI  - Keratouveitis caused by Euphorbia plant sap.
AB  - The milky sap or latex of Euphorbia plant is highly toxic and an irritant to the
      skin and eye. This report illustrates the spectrum of ocular inflammation caused
      by accidental inoculation of latex of Euphorbia plant. Three patients presented
      with accidental ocular exposure to the milky sap of Euphorbia species of recent
      onset. The initial symptoms in all cases were severe burning sensation with
      blurring of vision. Visual acuity reduced from 20/60 to counting fingers.
      Clinical findings varied from kerato-conjunctivitis, mild to severe corneal
      edema, epithelial defects, anterior uveitis and secondary elevated intraocular
      pressure. All symptoms and signs had resolved by 10-14 days with active
      supportive medication. People who handle Euphorbia plants should wear eye
      protection. It is always advisable to ask the patient to bring a sample of the
      plant for identification.

PMID- 19574705
TI  - Vision recovery in human immunodeficiency virus-infected patients with optic
      neuropathy treated with highly active antiretroviral therapy: a case series.
AB  - We describe three patients with bilateral, presumed human immunodeficiency virus
      (HIV)-induced optic neuropathy. The above diagnosis was made by exclusion of
      infectious agents and neoplasms by detailed clinical and laboratory
      investigations. All patients had decreased visual acuity, pale optic discs and
      constriction of visual fields. Improvement was documented in all three patients
      for visual acuity and in one patient for visual fields following treatment with
      highly active antiretroviral therapy (HAART). Optic neuropathy in HIV-positive
      patients does not necessarily carry a poor prognosis even when a treatable cause
      is not found. This article emphasizes the effectiveness of HAART in presumed HIV
      induced optic neuropathy.

PMID- 19574706
TI  - Schwannoma of the eyelid: apropos of two cases.
AB  - Schwannoma, also referred to as neurilemmoma, is a benign tumor of peripheral
      nerve arising from Schwann cells that form the neural sheath. Schwannoma of
      ophthalmic interest is rare although it has been reported in relation with the
      orbit, and less frequently with the uveal tract and conjunctiva. Isolated eyelid
      schwannoma is extremely uncommon. Up until now, only eight cases have been
      reported in literature. Herein, we report two cases of eyelid schwannoma.

PMID- 19574708
TI  - Microphthalmia and microcornea: in congenital cytomegalovirus.

PMID- 19574707
TI  - Fibrinous anterior uveitis following laser in situ keratomileusis.
AB  - A 29-year-old woman who underwent laser in situ keratomileusis (LASIK) for myopic
      astigmatism in both eyes presented with severe pain, photophobia and decreased
      visual acuity in the left eye eight days after surgery. Examination revealed
      severe anterior uveitis with fibrinous exudates in the anterior chamber, flap
      edema and epithelial bullae. Laboratory investigations for uveitis were negative
      and the patient required systemic and intensive topical steroids with
      cycloplegics to control the inflammation. This case demonstrates that severe
      anterior uveitis may develop after LASIK and needs prompt and vigorous management
      for resolution.

PMID- 19574709
TI  - Entrapment of intravitreal triamcinolone behind the crystalline lens.

PMID- 19574710
TI  - Retinitis pigmentosa associated with blepharophimosis, blue dot cataract and
      primary inferior oblique overaction: a new syndrome complex or consummate
      myotonic dystrophy?

PMID- 19574711
TI  - Polycythemia vera presenting with bilateral papilledema.

PMID- 19574712
TI  - Retinal pigment epithelium atrophy following indocyanine green dye-assisted
      surgery for serous macular detachment.

PMID- 19574713
TI  - Optical coherence tomography in a patient with chloroquine-induced maculopathy.

PMID- 19574714
TI  - Re-evaluation of the histological criteria for complete hydatidiform mole:
      Comparison with the immunohistochemical diagnosis using p57KIP2 and CD34.
AB  - Differential diagnosis between complete and partial hydatidiform mole is
      clinically important because of the difference in the risk of developing more
      malignant form of the molar diseases. In this report, the classical microscopic
      criteria were re-evaluated in the light of the immunohistochemistry of p57KIP2 in
      the attempt to establish robust morphological criteria for the differential
      diagnosis. Thirty-six consecutive cases clinically suspected to be hydatidiform
      mole were employed. The histological criteria were scored by three pathologists.
      The cases were categorized into three entities of the molar diseases in
      accordance with the immunohistochemistry of p57KIP2 and CD34. The diagnostic
      significance of the histological criteria was evaluated in a logistic regression
      model. Of 36 cases, the immunohistochemistry revealed that 28 were complete and 6
      were partial hydatidiform mole, while 2 cases were hydropic abortion. A stepwise
      logistic regression analysis indicated that, among seven criteria studied, three
      of them (shape of villi, prevalence of villi with three types of trophoblasts,
      and predominance of villi with hydropic change) were useful to differentiate
      complete hydatidiform mole from partial one. This observation may be applicable
      in the pathological diagnosis of the molar diseases.

PMID- 19574715
TI  - Expression of short-chain fatty acid receptor GPR41 in the human colon.
AB  - Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are
      the most commonly found anions found in the monogastric mammalian large
      intestine, and are known to have a variety of physiological and
      pathophysiological effects on the gastrointestinal tract. We investigated the
      protein and mRNA expression levels of GPR41, a possible G protein coupled
      receptor for SCFA, using Western blot analysis and reverse transcriptase
      polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in
      human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41
      protein is localized in cytoplasm of enterocytes and enteroendocrine cells.
      Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not
      serotonin or GPR43. The cellular population of GPR41 (0.01 +/- 0.01 cells/crypt)
      was much smaller than that of GPR43 (0.33 +/- 0.01 cells/crypt) in the human
      colon. However, the potency order of SCFA-induced phasic contraction of colonic
      smooth muscle that we previously reported is consistent with GPR41 (propionate
      >or= butyrate > acetate) but not GPR43 (propionate = butyrate = acetate).
      Therefore, the present study suggests that GPR41 expressed in human colonic
      mucosa may function as a sensor for luminal SCFAs.

PMID- 19574716
TI  - Acute stress augments innate immunity in the liver and increases hyaluronan
      levels in the tissues and blood of mice.
AB  - The effect of acute stress on the immune system was examined in mice. Restraint
      stress decreased the number of lymphocytes in the liver, whereas the number of
      lymphocytes remained unchanged in the spleen and thymus. In the liver, the
      decrease in number appeared at 1.5 h and fell to a third of he control level at 3
      h. The proportions of IL-2Rbeta(+)CD3(int) cells, NKT cells, CD44(+) T cells and
      B cells were changed in the liver. The absolute numbers of IL-2Rbeta(+)CD3(int)
      cells, NKT cells and CD3(+)CD44(+) cells remained constant in the liver under the
      stress, while those of total T cells and NK cells decreased. The levels of
      hyaluronan (HA) in various tissues and sera were then examined. The expression of
      hyaluronan binding protein (HABP) was found to increase in the skin, liver and
      kidney as shown by immunohistochemical staining. An increase of HA in sera due to
      stress was seen at 3 h. The present results suggest that the activation of
      CD44(+) T cells and unconventional T cells (i.e., innate immunity) in the blood
      and the elevated levels of HA (ligand for CD44) in the tissues and blood are
      crucial responses to acute stress exposure.

PMID- 19574717
TI  - DNase gamma-dependent and -independent apoptotic DNA fragmentations in Ramos
      Burkitt's lymphoma cell line.
AB  - DNA fragmentation is a biochemical hallmark of apoptosis. Several endonucleases,
      including CAD/DFF40 and endonuclease G, are implicated in DNA fragmentation.
      DNase gamma has also been considered to be one of the enzymes involved, but its
      role in relation to CAD/DFF40 in apoptosis has not been fully elucidated. Here,
      we distinguished between DNase gamma-dependent and CAD/DFF40-dependent DNA
      fragmentations. We found that DNase gamma activities appeared in the late
      apoptotic phase and accelerated DNA fragmentation. Thus, even if the apoptotic
      DNA fragmentation is initiated by CAD/DFF40, DNase gamma is required for the more
      complete digestion of the genomic DNA in dying cells.

PMID- 19574718
TI  - Is Stat3 and/or p53 mRNA expression a prognostic marker for renal cell carcinoma?
AB  - Signal transducer and activator of transcription (Stat) 3 and p53 integrate
      upstream signals, and are positive and negative regulators of tumor cell
      proliferation, respectively. Stat3 and p53 also negatively regulate each other.
      However, their roles remain elusive in patients with renal cell carcinoma (RCC).
      We quantified Stat3 and p53 mRNA expression in paired tumor and non-tumor
      surgical samples from 47 Japanese patients with RCC by the real-time reverse
      transcription polymerase chain reaction (RT-PCR) technique. Absolute levels of
      Stat3 and p53 mRNA were lower in tumor tissues compared with non-tumor tissues (P
      < 0.0001). The absolute levels of Stat3 and p53 mRNA in RCC tissue were not
      correlated with tumor histology, stage, or metastatic behavior. Kaplan-Meier
      analysis showed that a high level of Stat3 or p53 mRNA expression was associated
      with shorter overall survival compared to low expression (P = 0.254 and P =
      0.066, respectively). In addition, the tumor tissue levels of Stat3 and p53 mRNA
      expression were correlated with each other (r(2) = 0.697, P < 0.01). These
      findings suggest that Stat3 and p53 are cooperatively involved in the development
      of RCC, but assessment of their mRNA expression may not be useful for predicting
      the prognosis of patients with RCC.

PMID- 19574719
TI  - The anti-fibrotic agent SMP-534 attenuates bleomycin-induced pulmonary fibrosis
      in hamsters.
AB  - Pulmonary fibrosis is a progressive and lethal lung disease characterized by
      accumulation of ECM and loss of pulmonary function. However, no cure exists for
      this disease, and current treatments often fail to slow its progression or
      relieve its symptoms. We have previously reported that the anti-fibrotic agent
      SMP-534 has beneficial effects on renal fibrosis in animal model of nephropathy.
      In this study, we examined whether SMP-534 has beneficial effects on pulmonary
      fibrosis in bleomycin-treated hamsters. Treatment with SMP-534 [low dose (70
      mg/kg) or high dose (110 mg/kg)] counteracted inhibition of body weight increase
      induced by bleomycin. In addition, SMP-534 significantly inhibited bleomycin
      induced increase in lung hydroxyproline level, an index of collagen formation.
      Moreover, SMP-534 significantly ameliorated histological pulmonary fibrotic
      changes induced by bleomycin. The results of this study indicate that the anti
      fibrotic agent SMP-534 may offer a new therapeutic option for the treatment of
      pulmonary fibrosis.

PMID- 19574720
TI  - Heterogeneous expression of the voltage-gated calcium channel alpha2 subunit and
      the voltage-gated sodium channel alpha subunit in chicken spinal motoneurons.
AB  - The localization of the voltage-gated calcium channel (VGCC) alpha2 and the
      voltage-gated sodium channel (VGSC) alpha subunits was immunohistochemically
      investigated in chicken spinal motoneurons. Approximately 83% and 46% of spinal
      motoneurons were positive for VGCCalpha2 and VGSCalpha subunits, respectively.
      Almost all VGSCalpha subunit-positive motoneurons exhibited the VGCCalpha2
      subunit immunoreactivity. There were different patterns in occurrence, intensity
      or nuclear/cytoplasmic stainability of the VGCCalpha2 and VGSCalpha subunits
      among the motoneurons. This study presents the first cellular morphological
      evidence for the VGCCalpha2 and VGSCalpha subunits in spinal motoneurons,
      postulating that the heterogeneous expression of VGCCalpha2 and VGSCalpha
      subunits in the motoneurons may reflect various motor activities.

PMID- 19574721
TI  - Photocatalytic bactericidal action of fluorescent light in a titanium dioxide
      particle mixture: an in vitro study.
AB  - Traditional titanium dioxide (TiO(2)) has photocatalytic bactericidal properties
      only under ultraviolet (UV) irradiation, which restricts its use in clinical
      treatment regimens. In this study, we evaluated the photocatalytic bactericidal
      effects of an aqueous system of TiO(2) particles irradiated by fluorescent light
      (FL) on Staphylococcus aureus. A TiO(2) particle mixture containing 19 ppm (0.019
      mg/mL) of TiO(2) was prepared. A bacterial solution of 1 x 10(5) CFU/mL was added
      one drop at a time to the TiO(2) mixture. The resulting product was then
      irradiated with FL. The bacterial survival rate decreased steadily in the TiO(2)
      mixture group, reaching 76.7% after 30 min of FL irradiation and 10.9% after 60
      min. After 60 to 180 min, the bacterial survival ratio of the TiO(2) mixture
      group was significantly lower than that of the control group (P < 0.05). The
      present study indicates that treating the surfaces of surgical devices and the
      surgical field with a TiO(2) particle mixture can create a nearly sterile
      environment that can be maintained throughout surgery, even at low luminous
      intensities.

PMID- 19574722
TI  - Effects of extracellular chloride ion on epithelial sodium channel (ENaC) in
      arginine vasotocin (AVT)-stimulated renal epithelial cells.
AB  - The epithelial Na(+) channel (ENaC) contributes to control of blood pressure by
      reabsorbing Na(+) in the cortical collecting duct of the kidney. The luminal Cl(
      ) concentration in the duct varies under physiological conditions. As the body
      Na(+) content is lower, the luminal Cl(-) concentration in the duct becomes
      lower. Thus, we hypothesized that the extracellular Cl(-) elevates ENaC activity
      in AVT-stimulated renal epithelial A6 cells (a model cell line of the cortical
      collecting duct) leading to recovery from a low body Na(+) content. To clarify
      this point, we studied effects of extracellular Cl(-) concentration on ENaC
      activity using cell-attached patch clamp technique. We found that ENaC had a
      single-channel conductance of 4.6 +/- 0.1 pS (mean +/- SE) and channel activity
      (open probability, Po) of 0.30 +/- 0.02 at a pipette potential of 60 mV. Lowering
      pipette Cl(-) concentration diminished Po to 0.23 +/- 0.02 associated with a
      significant decrease in open time from 0.78 +/- 0.03 to 0.61 +/- 0.02 s with no
      significant change in closed time, and shifted the current-voltage relationship
      leftward. These results suggest that the extracellular Cl(-) regulates the ENaC
      mediated Na(+) reabsorption by affecting ENaC properties in AVT-stimulated renal
      epithelial cells.

PMID- 19574723
TI  - Drug-eluting stents. Insights from invasive imaging technologies.
AB  - Drug-eluting stents (DES) represent a revolutionary technology in their unique
      ability to provide both mechanical and biological solutions simultaneously to the
      target lesion. As a result of biological effects from the pharmacological agents
      and interaction of DES components with the arterial wall, considerable
      differences exist between DES and conventional bare metal stents (BMS), yet some
      of the old lessons learned in the BMS era remain clinically significant. In this
      context, contrast angiography provides very little information about in vivo
      device properties and their biomechanical effects on the arterial wall. In
      contrast, current catheter-based imaging tools, such as intravascular ultrasound,
      optical coherence tomography, and intracoronary angioscopy can offer unique
      insights into DES through direct assessment of the device and treated vessel in
      the clinical setting. This article reviews these insights from current DES with
      particular focus on performance and safety characteristics as well as discussing
      an optimal deployment technique, based upon findings obtained through the use of
      the invasive imaging technologies.

PMID- 19574724
TI  - A functional interleukin-1 receptor antagonist polymorphism influences
      atherosclerosis development. The interleukin-1beta:interleukin-1 receptor
      antagonist balance in atherosclerosis.
AB  - BACKGROUND: Interleukin (IL)-beta plays a central role in inflammation and
      atherosclerosis, but levels of IL-1beta, its natural antagonist, IL-1Ra, and
      their balance in human atherosclerotic lesions, are unknown. Knowledge of protein
      levels in atherosclerosis and the influence of a functional IL-1Ra polymorphism
      would increase the understanding of atherosclerosis pathogenesis. METHODS AND
      RESULTS: Fresh and endotoxin-stimulated explanted human atherosclerotic and
      normal arteries were analyzed for IL-1beta, IL-1Ra and IL-1 receptor 1 (IL-1R1)
      using TaqMan PCR and enzyme-linked immunosorbent assay. Two hundred forty-three
      survivors of a first myocardial infarction were genotyped for a polymorphism in
      IL-1Ra and their coronary atherosclerosis analyzed by using coronary angiography.
      Levels of IL-1beta, IL-1Ra and IL-1R1 mRNA were significantly increased in
      atherosclerotic arteries compared with normal arteries. Endotoxin stimulation
      increased IL-1beta levels more than IL-1Ra levels (ie, promoted a pro
      inflammatory state). A polymorphism in IL-1Ra known to increase levels of IL-1Ra
      was associated with decreased mean coronary artery plaque area. CONCLUSIONS:
      Activation of innate immunity changed the balance between IL-1beta and IL-1Ra in
      atherosclerotic arteries towards a more pro-inflammatory state. In line with
      this, the presence of an IL-1Ra intron 2 polymorphism known to increase IL-1Ra
      levels, and possibly the IL-1Ra:IL-1beta ratio, was associated with reduced
      coronary atherosclerosis.

PMID- 19574725
TI  - Evaluation of beta1L-adrenoceptors in rabbit heart by tissue segment binding
      assay.
AB  - [(3)H]-CGP12177 biphasically bound to beta-adrenoceptors with high and low
      affinities in the segments and crude membranes of rabbit left ventricle. The low
      affinity sites for [(3)H]-CGP12177 in the segments was double in density,
      compared to the density of high-affinity sites. Total abundance of the beta
      adrenoceptors decreased to approximately 10% upon tissue homogenization, and the
      proportion of low-affinity sites was the same as that of the high-affinity sites
      in the membranes. The majority of the high-affinity binding sites of [(3)H]
      CGP12177 in the segments and the membranes were beta(1H)-adrenoceptor, being
      highly sensitive to propranolol and beta(1)-antagonists (atenolol and ICI
      89,406), whereas the low-affinity binding sites showed a beta(1L)-profile (less
      sensitive to propranolol and beta(1)-, beta(2)-, and beta(3)-antagonists).
      Furthermore, a part of the beta(1L)-adrenoceptors was insensitive to atenolol,
      ICI-89,406, and/or isoproterenol. The present binding study clearly shows that
      beta(1L)-adrenoceptors occur as a distinct phenotype from beta(1H)-adrenoceptors
      in rabbit ventricle. However, quantitative imbalance between beta(1H)- and
      beta(1L)-adrenoceptors and divergent ligand-beta(1L)-adrenoceptor interactions
      suggest a possibility that the beta(1L)-adrenoceptor may not reflect a simple
      conformational change or allosteric state in the beta(1)-adrenoceptor molecule.

PMID- 19574726
TI  - Simultaneous assessment of pharmacokinetics of pilsicainide transdermal patch and
      its electropharmacological effects on atria of chronic atrioventricular block
      dogs.
AB  - Pharmacokinetics of pilsicainide transdermal patch and its electropharmacological
      effects were simultaneously assessed using chronic atrioventricular block dogs.
      After application of the patch (9.8 mg/kg), pilsicainide was continuously
      absorbed through the skin with a C(max) of 0.49 +/- 0.13 microg/ml, while its
      plasma concentration was kept above the clinically reported minimum effective
      plasma concentration for 2 - 8 h. Inter-atrial conduction time was significantly
      prolonged, whereas statistically significant prolongation was not detected in the
      atrial effective refractory period. Prolongation of the cycle length of atrial
      fibrillation and anti-fibrillatory action were confirmed. Thus, pilsicainide can
      be absorbed transdermally to exert long-lasting electropharmacological effects
      leading to anti-atrial fibrillatory action.

PMID- 19574727
TI  - The insulin gene variable number of tandemrepeats (INS VNTR)  genotype and sleep
      disordered breathing in childhood obesity.
AB  - Aim of our study is to verify the association between the genetic predisposition
      to hyperinsulinism due to the presence of the insulin gene (INS) I/I genotype and
      the development of sleep-related breathing disorders (SRBD) in obese children and
      adolescents. Two hundred and fifty-six obese children and adolescents (125 girls)
      have been investigated. As initial screening all subjects' mothers filled out the
      Sleep Disturbances Scale for Children (SDSC). The Sleep-Disordered Breathing
      (SDB) scale has been taken into account. Successively, a subgroup of 34 patients
      belonging to the first (14 children) and the last (20 children) SDB score
      quintiles underwent an overnight polysomnography and the apnea-hypopnea index
      (AHI) was evaluated. All subjects were genotyped for the INS VNTR and fasting
      insulin levels were evaluated. The population was divided into two groups
      according to the genotype: the first group was comprehensive of patients
      homozygotes for class I allele and the second group was composed by class III
      allele heterozygotes and homozygotes patients. Subjects I/I showed statistically
      signifIcant higher insulin levels (p<0.001) and SDB scores (p<0.001). Moreover,
      in the subgroup of patients investigated with polysomnography, class I homozygous
      subjects showed higher AHI compared to those patients carrying class III allele
      (p<0.001). Our data support the hypothesis that INS VNTR is associated with the
      development of SDB among obese children and adolescents.

PMID- 19574728
TI  - Glucose intolerance and risk of cardiovascular disease in Iranian men and women:
      results of the 7.6-year follow-up of the Tehran Lipid and Glucose Study (TLGS).
AB  - BACKGROUND: Despite the high prevalence of diabetes, limited information is
      available about the impact of impaired glucose regulation on the cardiovascular
      disease (CVD) risk among Middle East populations. AIMS: To determine the risk of
      CVD in an urban Iranian population according to glucose tolerance status.
      MATERIALS AND METHODS: The study population consisted of 1752 men and 2273 women,
      aged > or = 40 yr, free of CVD at baseline. Incident CVD was ascertained over a
      median of 7.6 yr of follow-up. RESULTS: A total of 340 CVD events occurred (197
      in men and 143 in women). At baseline, there was no difference between newly
      diagnosed and known diabetes regarding the Prospective Cardiovascular Munster
      (PROCAM) risk score and prevalence of metabolic syndrome in both genders.
      Applying the 1997 American Diabetes Association (ADA) criteria, compared with
      those with normal glucose tolerance, after controlling traditional risk factors,
      hazard ratios (HR) and 95% confidence intervals (95% CI) for CVD in women with
      known and newly diagnosed diabetes were 3.30 (2.09-5.21) and 1.93 (1.16-3.21) and
      the corresponding values for men were 1.90 (1.11-3.25) and 1.69 (1.12-2.54),
      respectively. Impaired fasting glucose or impaired glucose tolerance was
      associated with 56% increased risk of CVD in women (HR 1.56, 95% CI 1.00 to
      2.45), in the age-adjusted analysis, considering the 2003 ADA criteria.
      CONCLUSIONS: All diabetic subjects, whether newly diagnosed or known cases,
      should receive intensive primary prevention for CVD regardless of risk factors,
      in particular females with abnormal glucose regulation.

PMID- 19574730
TI  - Pluripotent stem cells isolated from human amniotic fluid and differentiation
      into pancreatic beta-cells.
AB  - Human amniotic fluid (HAF) contains multipotent stem cells [amniotic fluid
      derived stem cells (AFSC)] which can differentiate into a variety of different
      cell types. Recently, we demonstrated that obestatin, a peptide encoded by the
      ghrelin gene, exerts anti-apoptotic effects in pancreatic beta-cells and human
      islets and increases the expression of genes involved in beta-cells
      differentiation. We investigated whether: 1) AFSC would differentiate into
      pancreatic beta-cells and 2) obestatin would increase beta-cells differentiation
      from AFSC. Fluorescence-activated cell sorting analysis and immunocytochemical
      staining showed the presence of mesenchymal and endothelial markers in AFSC. Real
      time PCR evidenced the expression of Octamer binding transcription factor 4 (OCT
      4), a marker of pluripotency, during the early differentiation phase. However,
      the beta-cells differentiation marker duodenal homeobox factor-1 (PDX-1) could
      not be detected. Obestatin increased OCT-4 expression but had no effect on beta
      cells differentiation. These results suggest that, at least under the
      experimental conditions used in this study, AFSC do not differentiate into beta
      cells and obestatin has no additional effect.

PMID- 19574731
TI  - Association of five autoimmune diseases in a young woman with Down's syndrome.

PMID- 19574729
TI  - Endothelial function and endothelial nitric oxide synthase intron 4a/b
      polymorphism in primary hyperparathyroidism.
AB  - BACKGROUND AND AIM: Patients with symptomatic primary hyperparathyroidism (pHT)
      have increased cardiovascular morbidity and mortality. Endothelial nitric oxide
      synthase (eNOS) intron 4a/b polymorphism is associated with coronary artery
      disease and hypertension in various populations. Our aim is to evaluate
      endothelial function in patients with pHT during pre-operative hypercalcemic and
      post-operative normocalcemic periods and to determine whether intron 4a/b
      polymorphism of eNOS gene influences endothelial function. SUBJECTS AND METHODS:
      Forty patients with pHT (age 48.48+/-11.64 yr) were examined pre-operatively and
      reexamined 5.8+/-1.9 months after parathyroidectomy. Forty-three healthy subjects
      (age 47.13+/-8.14 yr) were served as control group. Endothelial function was
      determined by flow-mediated dilation of brachial artery (FMD). eNOS4a/b
      polymorphism was detected by polymerase chain reaction. RESULTS: FMD was
      significantly lower in patients pre-operatively compared with controls (8.48+/
      1.78% vs 19.49+/-2.34%, p<0.001). FMD improved significantly after
      parathyroidectomy (16.19+/-2.16%, p<0.001 compared with pre-operative
      measurements), but was still significantly lower than controls (p<0.001). The
      distribution of eNOS4a/b genotype frequencies was not significantly different
      between patients and controls. Logistic regression analysis showed that increased
      serum calcium (>2.47 mmol/l) and PTH concentrations (>7.75 pmol/l) were
      significant independent predictors of lower FMD (<16.7%). ENOS4a/b polymorphism
      did not enter in this model. CONCLUSION: Impaired endothelial function in
      patients with pHT improves after successful parathyroid surgery. No compelling
      data are evident to suggest that eNOS4a/b polymorphism modifies the endothelial
      function in patients with pHT.

PMID- 19574732
TI  - In their own words: interviews with Cell Cycle. The first knockout mouse model of
      retinoblastoma.

PMID- 19574733
TI  - Mechanisms of nuclear mRNA quality control.
AB  - Nuclear processing, packaging and export of mRNA transcripts are highly complex
      and coupled steps in eukaryotic gene expression that require mRNA quality
      control. During transcription, mRNAs must be capped, spliced and polyadenylated
      by processing factors. The processed mRNAs must also be loaded with numerous mRNA
      packaging and export factors to facilitate transport through nuclear pore
      complexes to the cytoplasm for translation. Given such complexity, mRNA
      production errors can lead to improperly processed/packaged mRNA transcripts that
      may be harmful to the cell if they are translated into defective proteins or
      deplete a functionally important gene product. To combat these aberrant mRNA
      transcripts, eukaryotic cells have evolved several nuclear and cytoplasmic mRNA
      quality control mechanisms that recognize and degrade incorrectly
      processed/packaged transcripts. Here we review recent progress in understanding
      evolutionarily conserved nuclear mRNA quality control mechanisms in the yeast
      Saccharomyces cerevisiae with particular emphasis on a novel mRNA quality control
      step at the nuclear pore.

PMID- 19574735
TI  - Activation gating kinetics of GIRK channels are mediated by cytoplasmic residues
      adjacent to transmembrane domains.
AB  - G-protein-coupled inwardly rectifying potassium channels (GIRK/Kir3.x) are
      involved in neurotransmission-mediated reduction of excitability. The gating
      mechanism following G protein activation of these channels likely proceeds from
      movement of inner transmembrane helices to allow K(+) ions movement through the
      pore of the channel. There is limited understanding of how the binding of G
      protein betagamma subunits to cytoplasmic regions of the channel transduces the
      signal to the transmembrane regions. In this study, we examined the molecular
      basis that governs the activation kinetics of these channels, using a chimeric
      approach. We identified two regions as being important in determining the
      kinetics of activation. One region is the bottom of the outer transmembrane helix
      (TM1) and the cytoplasmic domain immediately adjacent (the slide helix); and the
      second region is the bottom of the inner transmembrane helix (TM2) and the
      cytoplasmic domain immediately adjacent. Interestingly, both of these regions are
      sufficient in mediating the kinetics of fast activation gating. This result
      suggests that there is a cooperative movement of either one of these domains to
      allow fast and efficient activation gating of GIRK channels.

PMID- 19574736
TI  - Mechanistic details of BK channel inhibition by the intermediate conductance,
      Ca2+-activated K channel.
AB  - Salivary gland acinar cells have two types of Ca(2+)-activated K channels
      required for fluid secretion: the intermediate conductance (IK1) channel and the
      large conductance (BK) channel. Activation of IK1 inhibits BK channels including
      in small, cell-free, excised membrane patches. As a first step toward
      understanding the mechanism underlying this interaction, we examined its voltage
      sensitivity. We found that the IK1-induced inhibition of BK channels was only
      weakly voltage dependent and not accompanied by alteration in BK gating kinetics.
      These actions of IK1 on BK channels are not consistent with a mechanism whereby
      activation of IK1 causes a shift of the BK channel's voltage dependence as occurs
      for many BK modulatory processes. In a search for other clues about the
      interaction mechanism, we noted that the N-terminus of the IK1 channel shares
      some chemical features with the N-terminal regions of two BK subunits known to
      inhibit BK activity by blocking the cytoplasmic end of the BK pore. Thus, we
      tested the idea that the N-terminus of IK1 channels may act similarly. We found
      that a peptide derived from the N-terminal region of the IK1 protein blocked BK
      channels. Significantly, we also found that the activation of IK1 channels
      competed with block by the N-terminus peptide. Thus, the activation of IK1
      channels inhibits BK channels by a mechanism that involves block of the
      cytoplasmic pore, not an alteration in the voltage dependence of BK gating. The
      mediator of this cytoplasmic pore block may be the IK1 N-terminus.

PMID- 19574737
TI  - Crystal packing analysis of murine VDAC1 crystals in a lipidic environment
      reveals novel insights on oligomerization and orientation.
AB  - All eukaryotic cells require efficient trafficking of metabolites between the
      mitochondria and the rest of the cell. This exchange is carried out by the
      dominant protein in the outer mitochondrial membrane (OMM), the Voltage Dependent
      Anion Channel (VDAC), which serves as the primary pathway for the exchange of
      ions and metabolites between the cytoplasm and the intermembrane space of the
      mitochondria. Additionally, VDAC provides a scaffold for the binding of modulator
      proteins to the mitochondria and has been implicated in mitochondria-dependent
      cell death. We recently determined the structure of the murine VDAC1 (mVDAC1) at
      2.3 A resolution crystallized in a native-like bilayer environment. The high
      resolution structure provided concise structural details about the voltage
      sensing N-terminal domain and catalyzed new hypotheses regarding the gating
      mechanisms for metabolites and ions that transit the OMM. In this study, the
      crystal packing of mVDAC1 is analyzed revealing a strong antiparallel dimer that
      further assemble as hexamers mimicking the native oligomeric packing observed in
      EM and AFM images of the OMM. Oligomerization has been shown to be important for
      VDAC regulation and function, and mVDAC1 crystal packing in a lipidic medium
      reveals insights on how oligomerization is accomplished using protein-protein and
      protein-lipid interactions. Furthermore, orientation of VDAC in the OMM remains
      uncertain due to inconsistencies in antibody labeling studies. The physiological
      implications of a novel antiparallel arrangement are addressed that may clarify
      these conflicting biochemical data.

PMID- 19574738
TI  - The G(2) DNA damage checkpoint: could this ancient regulator be the Achilles heel
      of cancer?
AB  - The maintenance of genomic integrity is important in normal cell growth and
      organism development, as well as in the prevention of cancer. Cell cycle
      checkpoints allow the cell time to complete replication and repair DNA damage
      before it can pass to the next cell cycle stage. These checkpoints ensure
      faithful segregation of one undamaged copy of the genome to each daughter cell.
      In humans, a DNA damage-based checkpoint signal in G(1) is propagated through
      activation of the tumor suppressor p53, which is mutated in many cancers. Chk1, a
      serine/threonine kinase, controls checkpoint responses in G(2). Chk1 is activated
      by the concerted action of many upstream proteins and prevents a cell from
      entering mitosis with damaged or incompletely replicated DNA. This checkpoint is
      conserved from the fission yeast, Schizosaccharomyces pombe through to humans.
      However, unlike p53, G(2) checkpoint genes are rarely if ever mutated in cancer
      cells. This suggests that these genes are essential for tumor cell viability and
      may represent valid anti-cancer drug targets. This review will describe the
      current understanding of the G(2) checkpoint including how the human biology has
      been informed by studies in fission yeast. It will also discuss the present
      status and future of potential cancer therapies aimed at inactivating this
      signaling pathway in tumor cells.

PMID- 19574739
TI  - Targeting post-transcriptional control for drug discovery.
AB  - Post-transcriptional regulatory mechanisms, dependent on specific RNA:RNA,
      RNA:protein, or protein:protein interactions that generate large numbers of
      different RNP constellations, can have sizeable effects on the expression of any
      given gene. At the mRNA-specific level, these mechanisms also provide numerous
      novel targets for small molecule drugs capable of enhancing or inhibiting the
      accumulation of specific proteins. Here, we describe two drug screening
      technologies that target the post-transcriptional regulation of specific mRNAs
      with specific small molecules. In one case the GEMS technology utilizes mRNA
      specific 5'- and 3'-UTR pairs to identify compounds that reduce protein
      production as a consequence of the UTRs. The second example utilizes nonsense
      containing mRNAs to identify compounds capable of promoting therapeutic nonsense
      suppression. Both programs have yielded drug candidates that are presently in
      clinical testing for human diseases with high unmet clinical needs, thus
      illustrating the therapeutic potential of targeting post-transcriptional control.

PMID- 19574741
TI  - Nurses making a difference: taking personal responsibility for using research
      findings.

PMID- 19574744
TI  - Notes from the net nomad...

PMID- 19574740
TI  - TRPC channels as STIM1-regulated SOCs.
AB  - Store-operated Ca(2+) channels (SOCs) are Ca(2+) influx channels at the plasma
      membrane whose opening is determined by the level of Ca(2+) stored in the
      endoplasmic reticulum lumen. SOCs are activated in response to receptor-mediated
      or passive depletion of ER Ca(2+) to regulate many Ca(2+)-dependent cellular
      functions. Early work implicated the TRPC channels as SOCs. More recently, it was
      found that the Orai channels mediate the CRAC current and that the Ca(2+) binding
      protein STIM1 functions as the ER Ca(2+) sensor that mediates activation of the
      SOCs in response to depletion of ER Ca(2+). Key questions are whether both TRPC
      and Orai channels are opened by STIM1 and the molecular mechanism by which STIM1
      opens the SOCs. Ample biochemical and functional evidence indicate interaction of
      the TRPC channels with STIM1. Furthermore, it was found that STIM1 gates TRPC
      channels by electrostatic interaction of STIM1(K684,K685) in the polybasic domain
      of STIM1 with two negative charges (aspartates or glutamates) that are conserved
      in all TRPC channels. Charge mutants of STIM1(K684,K685) and TRPC1(D639,D640) and
      TRPC3(D697,D698) were used to develop further direct evidence for the function of
      TRPC channels as SOCs. The evidence in favor of TRPC channels as SOCs are
      discussed.

PMID- 19574745
TI  - Rural hospital information technology implementation for safety and quality
      improvement: lessons learned.
AB  - This grant involved a hospital collaborative for excellence using information
      technology over 3-year period. The project activities focused on the improvement
      of patient care safety and quality in Southern rural and small community
      hospitals through the use of technology and education. The technology component
      of the design involved the implementation of a Web-based business analytic tool
      that allows hospitals to view data, create reports, and analyze their safety and
      quality data. Through a preimplementation and postimplementation comparative
      design, the focus of the implementation team was twofold: to recruit participant
      hospitals and to implement the technology at each of the 66 hospital sites. Rural
      hospitals were defined as acute care hospitals located in a county with a
      population of less than 100 000 or a state-administered Critical Access Hospital,
      making the total study population target 188 hospitals. Lessons learned during
      the information technology implementation of these hospitals are reflective of
      the unique culture, financial characteristics, organizational structure, and
      technology architecture of rural hospitals. Specific steps such as recruitment,
      information technology assessment, conference calls for project planning, data
      file extraction and transfer, technology training, use of e-mail, use of
      telephones, personnel management, and engaging information technology vendors
      were found to vary greatly among hospitals.

PMID- 19574746
TI  - Exploring the ability of natural language processing to extract data from nursing
      narratives.
AB  - Natural Language Processing (NLP) offers an approach for capturing data from
      narratives and creating structured reports for further computer processing. We
      explored the ability of a NLP system, Medical Language Extraction and Encoding
      (MedLEE), on nursing narratives. MedLEE extracted 490 concepts from narrative
      text in a sample of 553 oncology nursing process notes. The most frequently
      monitored and recorded signs and symptoms were related to chemotherapy care, such
      as adverse reactions, shortness of breath, nausea, pain, and bleeding. In terms
      of nursing interventions, chemotherapy, blood culture, medication, and blood
      transfusion were commonly recorded in free text. NLP may provide a feasible
      approach to extract data related to patient safety/quality measures and nursing
      outcomes by capturing nursing concepts that are not recorded through structured
      data entry. For better NLP performance in the domain of nursing, additional
      nursing terms and abbreviations must be added to MedLEE's lexicon.

PMID- 19574748
TI  - Internet addiction and interpersonal problems in korean adolescents.
AB  - The purpose of this study was to examine the levels of Internet addiction and
      interpersonal problems, explore the relationship between the two, and identify
      the relevant factors of Internet addiction in Korean middle school students. A
      cross-sectional survey design was used. The participants were 676 middle school
      students. A Korean version of the Internet addiction self-test scale and a Korean
      version of the Inventory of Interpersonal Problems were used. Among the
      participants, 547 (80.9%) were identified as general users, 108 (16%) were
      potential risk users, and 21 (3.1%) were high-risk users. There were
      statistically significant positive correlations between Internet addiction and
      interpersonal problems (r = 0.425, P = .000). There were significant positive
      correlations between Internet addiction and hours spent playing games. Internet
      addicted adolescents also had more interpersonal problems. It is important to
      raise awareness about Internet addiction, and close attention must be paid not
      only to students at risk of Internet addiction but also to students at low risk
      to prevent students from becoming addicted to the Internet.

PMID- 19574749
TI  - Developing an electronic nursing record system for clinical care and nursing
      effectiveness research in a korean home healthcare setting.
AB  - Increased accountability requirements for the cost and quality of healthcare
      force nurses to clearly define and verify nursing's contributions to patient
      outcomes. This demand necessitates documentation of nursing care in a precise
      manner. An electronic nursing record system is considered a key element that
      enhances nurses' ability not only to record nursing care provided to patients but
      also to measure, report, and monitor quality and effectiveness. Home care is a
      growing field as nurses attempt to meet the demand for long-term care. The
      development of an electronic record system for home care nursing was the
      immediate focus of this study. We identified the nursing content required for
      home care nursing using standardized nursing languages and designed linkages
      among medical diagnoses, nursing diagnoses, nursing interventions, and nursing
      sensitive outcomes within the system. Equipping an electronic nursing record
      system with nursing standards is particularly critical for enhancing nursing
      practice and for creating refined data to verify nursing effectiveness.

PMID- 19574750
TI  - The multimethod evaluation of a nursing information system in taiwan.
AB  - The purpose of this study was to evaluate the impact of a nursing information
      system on nurses' daily practice. A multimethod evaluation was used that combined
      both quantitative and qualitative approaches to explore the influence of this
      technology from different perspectives. The data collection methods included the
      following: an evaluation scale of the system function, focus group interviews
      about the users' experiences, and work sampling observation of their work
      pattern. The data were collected from October to December 2006. The data analysis
      contained 623 valid questionnaires, 24 nurses' interview content, and 22830
      observed nursing activities. Overall, the results indicated that nurses gave a
      positive evaluation of the technology in their work routine. However, they were
      concerned about the inadequacy of the hardware devices and response time,
      training and workflow change, and personal interactions with physicians and
      patients. Nurses on the night shift spent more time on documentation than on any
      other nursing activities during the three shifts. The users' technology adoption
      could be attributed to device sufficiency and function, content design, and
      workflow efficiency. It is recommended that organizations provide sufficient
      computer devices, ensure the content design for nursing documentation, and
      implement expectations for interdisciplinary cooperation.

PMID- 19574751
TI  - Evaluation of an innovative communication technology in an acute care setting.
AB  - Wireless technology in healthcare has been associated with communication-related
      improvements in workflow; however, there are barriers to adoption. The purpose of
      this study was to assess perceptions and attitudes of staff toward the use of a
      wireless communication device (Vocera, Vocera Communications, Inc., San Jose, CA)
      and to compare communication patterns before and after implementation. A pretest
      posttest quasi-experimental design and the Theory of Planned Behavior were used.
      Attitudes, subjective norms, and perceived control explained 25% of the variation
      in behavioral intent before and 45% of the variation in behavioral intent after
      Vocera implementation. The time for key communication activities was reduced by
      25% overall. On average, each nurse engaged in these activities 16.2 times a day
      before Vocera and 11.6 times a day with Vocera. This study provides evidence that
      introduction of novel communication technology must account for user attitudes
      before implementation. Vocera improved "hand-off" communication, was perceived to
      be of benefit, and has the potential to improve patient safety and work
      environments. This may also translate to reduction in healthcare resources.

PMID- 19574752
TI  - American medical informatics association nursing informatics history committee
      update.

PMID- 19574753
TI  - Technology Informatics Guiding Education Reform Moves Into Phase III:
      Implementation.

PMID- 19574754
TI  - Alliance for nursing informatics provides key elements for "meaningful use"
      dialogue.

PMID- 19574755
TI  - Insights on overeating and health.

PMID- 19574758
TI  - Twittering about anything, everything, and even health.

PMID- 19574756
TI  - An Ayurvedic approach to postpartum depression.
AB  - Ayurvedic medicine has existed for more than 5000 years but is only recently
      receiving recognition in current medical literature. The purpose of this article
      is to present an overview of Ayurvedic medicine, describe Ayurvedic treatment of
      postpartum depression, discuss concerns about herbal preparations, and discuss
      implications for nursing practice and research.

PMID- 19574759
TI  - The intentionality of compassion energy.
AB  - Compassion energy is the converse of compassion fatigue. Nurses will grow and
      thrive if they understand how to self-generate vigor as compassion energy,
      preventing compassion fatigue or burnout. The compassion energy experience can
      elicit implications for nursing practice to add to the caring process.

PMID- 19574760
TI  - Understanding homelessness using a simulated nursing experience.
AB  - Students have an opportunity to understand the full experience of being homeless
      using simulated community nursing situations with a high-fidelity simulator. The
      Community Nursing Practice Model provides a context for using this innovative
      teaching strategy to enable students to respond holistically to the needs of the
      homeless.

PMID- 19574761
TI  - Effectiveness of music therapy for anxiety reduction in women with breast cancer
      in chemotherapy treatment.
AB  - In the last decade, the public use of complementary and alternative therapies for
      the solution of various health problems has increased dramatically. Listening to
      music can be considered a support to the traditional medical practice for the
      reduction of anxiety and stress related to chemotherapy.

PMID- 19574762
TI  - Swedish nurses' experiences of caring for dying people: a holistic approach.
AB  - Most people need to be cared for at the end of their lives by professionals. This
      study aimed to elucidate the meaning of nurses' experiences of caring for dying
      persons at home and in a special unit in a hospital. Four registered nurses
      working in private homes and 4 registered nurses working in a specific unit in a
      hospital setting were interviewed. The study was planned and carried out with a
      phenomenological hermeneutic approach. A naive reading guided a structural
      analysis, which resulted in 3 main themes: meeting patients and family members as
      unique persons, learning in a challenging environment, and gaining personal
      strength. The interpreted comprehensive understanding conveyed a meaning that
      caring for families with a member awaiting the end of life created a situation
      where the presence of an inevitable death demanded nurses to create close
      relationships with each unique person involved.

PMID- 19574763
TI  - Sleep disorders: a single dose administration of valerian/hops fluid extract
      (dormeasan) is found to be effective in improving sleep.

PMID- 19574764
TI  - Looking forward to our growth in readership and quality.

PMID- 19574765
TI  - Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy
      in an ex vivo human ovarian cancer model.
AB  - OBJECTIVES: To investigate the cytotoxicity of TRA-8, an antibody that
      specifically binds death receptor 5, alone and in combination with chemotherapy,
      using an ex vivo human ovarian cancer model. MATERIALS AND METHODS: Twenty-six
      ovarian cancer specimens were obtained during ovarian cancer debulking, and tumor
      slices were prepared with the Krumdieck tissue slicer. The tumor slices were
      exposed to varying concentrations of TRA-8, carboplatin/paclitaxel, or the
      combination of TRA-8 and chemotherapy. Using nonlinear modeling, dose-response
      curves and IC50 values were generated for specimens treated with TRA-8. The
      additive and synergistic cytotoxic effects of chemotherapy combination with TRA-8
      were evaluated in specimens. In addition to adenosine triphosphate viability
      assays, the treated and untreated slices were assessed by immunohistochemistry to
      confirm apoptosis induction. RESULTS: Specimens from 13 patients yielded TRA-8
      induced IC50 values. Of these specimens, 15% were found to be sensitive to TRA-8
      induced cytotoxicity at IC50 doses less than 500 ng/mL. Specimens from 13
      patients underwent combination treatment with TRA-8 and carboplatin/paclitaxel.
      Of these specimens, 77% exhibited additive cytotoxicity in comparison with those
      treated with either agent alone, whereas 15% exhibited synergistic cytotoxicity.
      Immunohistochemical analysis of terminal deoxynucleotidyl transferase biotin-dUTP
      nick end labeling and cleaved caspase 3 staining demonstrated a dose-dependent
      increase in apoptosis with the combination treatment. CONCLUSIONS: This study
      demonstrates the efficacy of the death receptor monoclonal antibody TRA-8 in
      combination with conventional chemotherapy in an ex vivo human ovarian cancer
      model. This model can be used to assess cytotoxicity of novel agents in
      combination with chemotherapy in ovarian cancer.

PMID- 19574766
TI  - The relationship of platinum resistance and ERCC1 protein expression in
      epithelial ovarian cancer.
AB  - OBJECTIVE: Although platinum-based chemotherapy remains the cornerstone for
      treatment of ovarian cancer, some patients are resistant to the treatment and
      will therefore not benefit from the standard platinum-based chemotherapy.
      Preclinical and clinical data have suggested a potential use of excision repair
      cross-complementation group 1 enzyme (ERCC1) as a molecular predictor of clinical
      resistance to platinum-based chemotherapy. Excision repair cross-complementation
      group 1 enzyme is a key enzyme in the nucleotide excision repair pathway which is
      involved in the DNA repair mechanisms in tumor cells damaged by treatment with
      platinum agents. The primary aim of the present study was to investigate if
      immunohistochemical expression of ERCC1 protein was associated with resistance to
      standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed
      ovarian cancer patients. METHODS: Formalin-fixed, paraffin-embedded tissue
      sections from 101 patients with newly diagnosed ovarian cancer were used for
      immunohistochemical staining for the ERCC1 protein. All patients received
      carboplatin-paclitaxel combination chemotherapy. RESULTS: Excision repair cross
      complementation group 1 enzyme protein overexpression was found in 13.9% of the
      tumors. Platinum resistance was found in 75% of the tumors with positive ERCC1
      protein expression compared with 27% among the patients with negative tumor
      staining for ERCC1 (P = 0.0013). These findings translated into a significant
      difference in progression-free survival in both univariate (P = 0.0012) and in
      multivariate analysis (P = 0.006). CONCLUSIONS: The data presented suggest a
      positive association between positive ERCC1 protein expression and clinical
      resistance to platinum-based chemotherapy.

PMID- 19574767
TI  - High rates of occult fallopian tube cancer diagnosed at prophylactic bilateral
      salpingo-oophorectomy.
AB  - OBJECTIVE: To determine the rate of occult malignancy in patients undergoing
      prophylactic bilateral salpingo-oophorectomy in Northern Sydney. METHODS: A
      retrospective case series of 45 consecutive patients who underwent prophylactic
      bilateral salpingo-oophorectomy between 2004 and March 2008. RESULTS: Five (11%)
      cases of occult neoplasia were found in 45 patients. This included 3 cases of
      micro-invasive serous carcinoma of the fallopian tube, 1 case of in situ
      carcinoma in the fallopian tube and 1 case of metastatic breast cancer in the
      ovary. All cases of primary neoplasia were in the fimbrial end of the fallopian
      tube. CONCLUSIONS: The importance of complete removal of the fallopian tubes and
      ovaries and the rigorous systematic pathological examination of these specimens
      are demonstrated in this case series. It supports emerging evidence that the
      fimbrial end of the fallopian tube is an important site of genesis of cancer in
      BRCA1/2 mutation carriers.

PMID- 19574768
TI  - Promising effect of aromatase inhibitors on recurrent granulosa cell tumors.
AB  - Recurring adult-type granulosa cell tumors of the ovary are usually treated by
      surgical resection followed by chemotherapy or radiation. However, the results of
      such treatment are disappointing. We describe 4 patients in whom recurrent
      ovarian granulosa cell tumors were treated with an aromatase inhibitor, with
      promising results.

PMID- 19574769
TI  - Phase II study of intraperitoneal carboplatin with intravenous paclitaxel in
      patients with suboptimal residual epithelial ovarian or primary peritoneal
      cancer: a Sankai Gynecology Cancer Study Group Study.
AB  - PURPOSE: To assess the antitumor efficacy and safety of 2 treatment modalities:
      intraperitoneal carboplatin combined with intravenous (IV) paclitaxel. PATIENTS
      AND METHODS: Eligible patients were those with epithelial ovarian carcinoma or
      primary peritoneal carcinoma stages II to IV who underwent initial surgery and
      had a residual tumor size of 2 cm or larger. Patients received IV paclitaxel 175
      mg/m followed by intraperitoneal carboplatin AUC6. The primary end point was a
      response. Secondary end points were toxicity, progression-free survival, and
      overall survival. RESULTS: Twenty-six patients were enrolled, and 24 patients
      were eligible for assessment. The response rate was 83.3% (95% CI, 62.6%-95.3%;
      ). The median progression-free survival was 25 months. The median overall
      survival had not been reached. Incidences of grade (G) 3/4 hematological
      toxicities were absolute neutrophil count, 96%; hemoglobin, 29%; and
      thrombocytopenia, 16%. Nonhematological toxicities included G2 liver function,
      4%; G3 sensory neuropathy, 8%; and G3 myalgia and arthralgia, 4%. CONCLUSIONS:
      Intraperitoneal administration of carboplatin combined with IV paclitaxel was
      well tolerated and showed satisfactory response in the patients with bulky
      residual tumor. Large-scale phase III trial comparing with IV carboplatin is
      warranted in this patient population.

PMID- 19574770
TI  - The level of RCAS1 expression is inversely correlated with the number of vimentin
      positive stromal cells in epithelial ovarian cancer.
AB  - Expression of RCAS1 is significantly associated with clinical prognosis in 15
      different types of human cancer. We have previously reported that RCAS1
      expression is correlated with a decreasing number of vimentin-positive stromal
      cells in cervical cancer. Moreover, RCAS1 expression is related to the expression
      of matrix metalloprotease 1 and laminin 5 and angiogenesis. We examined whether
      RCAS1 contributes to connective tissue remodeling in epithelial ovarian cancer.
      RCAS1 expression was studied retrospectively via immunohistochemistry. Samples
      were obtained from resected tumor tissues from 65 patients with epithelial
      ovarian cancer. Statistical analysis was done to correlate RCAS1 expression and
      clinicopathologic variables. The associations between RCAS1 expression and the
      number of vimentin-positive cells or microvessel density were evaluated. Western
      blot analysis was also performed to verify the perturbation of vimentin
      expression in fibroblast L cells, following stimulation by soluble RCAS1. RCAS1
      expression was detected in 72.3% (47/65 total cases) and significantly correlated
      with age and histological subtype. Patients with advanced stage, positive lymph
      node metastasis, or positive peritoneal cytological results had significantly
      shorter overall survival rates; however, no significant relationship was detected
      between RCAS1 immunoreactivity and overall survival. In the connective tissue
      surrounding tumor cells, the number of cells expressing vimentin significantly
      decreased in relation to the RCAS1 expression level. The growth of L cells was
      suppressed after stimulation by soluble RCAS1, and the expression of vimentin was
      markedly diminished. RCAS1 may contribute to connective tissue remodeling by
      altering the number of vimentin-positive cells in epithelial ovarian cancer.

PMID- 19574771
TI  - Primary psammocarcinoma of the ovary or peritoneum.
AB  - BACKGROUND: The aim of this study was to assess the outcomes of patients treated
      for peritoneal or ovarian psammocarcinoma (PSC). MATERIALS AND METHODS: Review of
      patients with PSC who underwent cytoreductive surgery in our institution with a
      follow-up of more than 18 months (the ovarian or peritoneal tumor was
      histologically reviewed by our reference pathologist). RESULTS: From 1997 to
      2006, 15 patients with PSC were histologically reviewed in our institution. Five
      of these patients fulfilled the inclusion criteria. Four patients had ovarian
      PSC, and 1 had peritoneal PSC. Four patients were surgically treated during
      initial management and another patient at the time of recurrence. All of them
      underwent complete cytoreductive surgery followed by intraperitoneal chemotherapy
      in 2 patients and by conventional adjuvant chemotherapy in 1. After a median
      follow-up of 42 months, 4 of them remain disease-free. CONCLUSIONS: Peritoneal or
      ovarian PSC is a rare low-grade carcinoma characterized by a more favorable
      prognosis than classic carcinoma. The place of debulking surgery at the time of
      initial or recurrent management is important.

PMID- 19574772
TI  - The role of inhibins B and antimullerian hormone for diagnosis and follow-up of
      granulosa cell tumors.
AB  - The peptide hormones inhibin and antimullerian hormone (AMH), both produced by
      the granulosa cells, are potential candidates for diagnosis and follow-up of
      granulosa cell tumors (GCTs). The objective was to evaluate the usefulness of
      serum levels of inhibin B and AMH in the diagnosis and follow-up of GCT. The
      review summarizes and discusses the value and limitations of the laboratory tests
      of these hormones by investigating the performance characteristics of the serum
      analyses. A search in PubMed database was accomplished to find articles
      describing serum inhibin and/or AMH as a diagnostic test or for follow-up of GCT.
      The literature search included articles published between 1989 and September
      2008. The sensitivity of inhibin B and AMH for diagnosing patients with a
      progressive disease is rather equivalent. Antimullerian hormone is a more
      specific serum parameter than inhibin, because inhibin may also increase in some
      (mucinous) epithelial ovarian tumors. Nowadays, specific and ultrasensitive
      assays are commercially available as well for inhibin B as for AMH, so that early
      detection of GCT might be possible. For patients with elevated levels of inhibin
      B and/or AMH at initial diagnosis of GCT, inhibin B and/or AMH seemed to be
      reliable markers during follow-up for early detection of residual or recurrent
      disease. Elevated concentrations of these hormones predict relapse earlier than
      clinical symptoms, which leads to less morbidity of the patients. In conclusion,
      inhibin B and AMH are both useful serum markers for diagnosis and especially for
      follow-up of patients with a GCT. Currently, there is no evidence-based
      preference for inhibin B or AMH as tumor marker.

PMID- 19574773
TI  - Brain metastases in epithelial ovarian and primary peritoneal carcinoma.
AB  - OBJECTIVES: Central nervous system metastases are believed to be becoming more
      clinically evident as long-term survival for epithelial ovarian cancer (EOC) and
      primary peritoneal cancer (PPC) has improved. Our objective was to report our
      experience with managing brain metastatic disease (BMD) in patients with EOC and
      PPC. METHODS: A retrospective review was performed on patients with EOC and PPC
      diagnosed with BMD from 1983 to 2007 at our institution. RESULTS: Twenty-four
      patients were identified. Patients with multiple brain lesions (n = 16) had a
      shorter median time to diagnosis of BMD than patients with single lesions (n = 8;
      22.5 vs 39 months). Radiation therapy was included in the treatment of BMD for 19
      patients (78%). Fourteen patients received whole-brain radiation therapy (WBRT)
      only (survival, 6 months [range, 1-51 months]). Three patients received a
      combination of gamma knife radiosurgery and WBRT (survival, 20 months [range, 17
      67 months]), and 1 patient received gamma knife radiosurgery alone (survival, 10
      months). Four patients underwent craniotomy with 3 receiving postoperative WBRT
      (survival, 8.5 months [range, 2-97 months]). Two patients elected for palliative
      care only. The median survival from the diagnosis of BMD was 8.5 months (range, 1
      97 months) with a 42% 1-year survival and 16% 2-year survival. Patients with
      single lesions had a significantly longer survival than patients with multiple
      lesions (17 months [range, 3-97 months] vs 6 months [range, 3-67 months],
      respectively). CONCLUSIONS: Our report provides the largest single-institution
      experience of brain metastasis from EOC and PPC in patients receiving
      predominantly platinum and paclitaxel therapy. Patients with BMD from EOC and PPC
      have a poor prognosis overall; however, prolonged survival is possible in a small
      subset of patients.

PMID- 19574774
TI  - Overexpression of epithelial cell adhesion molecule in primary, metastatic, and
      recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for
      epithelial cell adhesion molecule-specific immunotherapy.
AB  - To evaluate the potential of epithelial cell adhesion molecule (Ep-CAM/TROP-1)
      specific immunotherapy against epithelial ovarian carcinomas (EOCs), we have
      analyzed the expression of Ep-CAM at RNA and protein level in patients harboring
      primary, metastatic, and chemotherapy-resistant/recurrent EOC. Epithelial cell
      adhesion molecule expression was evaluated by real-time polymerase chain reaction
      and immunohistochemistry in 168 fresh-frozen biopsies and paraffin-embedded
      tissues. In addition, Ep-CAM surface expression was evaluated by flow cytometry
      in several freshly established ovarian carcinoma cell lines derived from patients
      harboring tumors resistant to chemotherapy in vivo as well as in vitro.
      Epithelial cell adhesion molecule transcript was found significantly
      overexpressed in primary, metastatic, and recurrent EOC when compared with normal
      human ovarian surface epithelium cell lines and fresh-frozen normal ovarian
      tissue (P < 0.001). Similarly, by immunohistochemistry, Ep-CAM protein expression
      was found significantly higher in primary, metastatic, and recurrent EOC when
      compared with normal ovarian tissues. Of interest, metastatic/recurrent tumors
      were found to express significantly higher levels of Ep-CAM protein when compared
      with primary ovarian carcinomas (P < 0.001). Finally, a high surface expression
      of Ep-CAM was found in 100% (5/5) of the chemotherapy-resistant ovarian carcinoma
      cell lines studied by flow cytometry. These results demonstrate high Ep-CAM
      overexpression in ovarian carcinoma, especially in metastatic and
      recurrent/chemotherapy-resistant ovarian disease. The lack of Ep-CAM expression
      on the chelomic epithelium in the peritoneal cavity, combined with the recent
      development of fully human monoclonal antibodies against this surface molecule,
      suggest Ep-CAM as a promising target for antibody-mediated therapies in ovarian
      carcinoma patients harboring tumors refractory to standard treatment modalities.

PMID- 19574775
TI  - Adnexal mass vascularity assessed by 3-dimensional power Doppler: does it add to
      the risk of malignancy index in prediction of ovarian malignancy?: four hundred
      case study.
AB  - The Risk of Malignancy Index (RMI) is used for the prediction of ovarian
      malignancy. It includes menopausal status, carbohydrate antigen 125 serum levels,
      and ultrasound criteria. Three-dimensional power Doppler (3-DPD) is a
      reproducible investigation for assessment of tumor vascularity, classifying
      vascularity to avascular, parallel, and chaotic patterns. In this study; 3-DPD
      was added to RMI for prediction of malignancy in 400 cases of ovarian masses.
      Sensitivity of RMI for prediction of malignancy was 88%, with a cutoff value of
      202.5 at 95% confidence interval. Sensitivity of 3-DPD for prediction of
      malignancy was 75%, adding 3-DPD to RMI increased its sensitivity to 99%.
      Considering the pilot nature of the study, further studies are needed to
      corroborate such findings.

PMID- 19574776
TI  - Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer: a
      controlled randomized study.
AB  - The purpose of the study was to compare postoperative vaginal irradiation with
      surgery alone in low-risk International Federation of Gynecology and Obstetrics
      (FIGO) stage IA-IB endometrial carcinoma. The study was a prospective, randomized
      trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European
      gynecologic cancer centers. All tumors were in FIGO stage IA-IB, of endometrioid
      histological type, and FIGO grade 1-2. High-dose-rate afterloading equipments
      (iridium [Ir] 192 or cobalt [co] 60) were used at 5 centers, and low-dose-rate
      (LDR) afterloading equipment (cesium [Cs] 137) at 1 center. Perspex vaginal
      applicators or ovoids were normally used, and the dose was specified at 5 mm from
      the surface of the applicator. Three to 6 fractions (3.0-8.0 Gy) were given, and
      the overall treatment time was 4 to 15 days. A total of 319 patients were treated
      with surgery plus vaginal irradiation (treatment group), and 326 patients with
      surgery alone (control group).Twenty-six recurrences (4.0%) were recorded in the
      complete series. The locoregional recurrence rate was 2.6%, whereas distant
      metastases occurred in 1.4%. The rate of vaginal recurrences was 1.2% in the
      treatment group versus 3.1% in the control group. The difference was not
      statistically significant (P = 0.114). Side effects were few and mild (grade 1
      2). Dysuria, frequency, and incontinence were slightly more common after vaginal
      irradiation (2.8% vs 0.6%, respectively). Late intestinal problems were few and
      similar in the 2 groups. The conclusions were that the impact of postoperative
      brachytherapy on even the locoregional recurrence rate seems to be limited in
      patients with low-risk endometrial carcinoma. The overall recurrence rate and
      survival were similar in the 2 groups.

PMID- 19574777
TI  - A comparison of perioperative morbidity, perioperative mortality, and disease
      specific survival in elderly women (>or=70 years) versus younger women (<70
      years) with endometrioid endometrial cancer.
AB  - OBJECTIVE: The study compares the perioperative morbidity and mortality rates of
      elderly (>or=70 years) and younger (<70 years) patients with endometrioid
      endometrial cancer. METHODS: The study cohort consisted of 115 consecutive women
      undergoing explorative laparotomy because of endometrioid endometrial cancer.
      Clinical data included patients' age, comorbidities, chronic use of medications,
      body mass index (kg/m), previous surgical procedures, surgical International
      Federation of Gynecology and Obstetrics stage, histological grade, relevant
      prognostic factors, a number of dissected lymph nodes, occurrence of
      perioperative complications, postoperative hospital stay (in days), and long-term
      disease-specific survival (in months). RESULTS: Patients were divided into 2
      groups: those younger than 70 years (group 1: 84 women, 73%) and those 70 years
      or older (group 2: 31 women, 27%). Although, as expected, elderly women had more
      major comorbidities, the rate of perioperative complications was similar between
      the 2 groups. In a logistic regression model, only chronic lung disease,
      gastrointestinal disease, and past abdominal surgery correlated with a higher
      rate of perioperative complications. None of the cohort patients died during the
      perioperative period. The long-term disease-specific survival was significantly
      poorer for the older group. CONCLUSION: Chronological age by itself should not be
      a contraindication for the proper surgical treatment of elderly women with
      endometrioid endometrial cancer, because it is a poor predicting factor for
      perioperative morbidity and mortality.

PMID- 19574778
TI  - Preoperative and intraoperative assessments of depth of myometrial invasion in
      endometrial cancer.
AB  - OBJECTIVE: Preoperative and intraoperative assessments of myometrial invasion
      (MI) are commonly used for planning surgical procedures such as dissection of the
      para-aortic node; however, the assessments often differ from the final diagnosis
      determined by pathological examination. The present study evaluated the accuracy
      of preoperative and intraoperative assessments of MI. METHODS: A total of 191
      patients with endometrial cancer, who underwent hysterectomy from 1995 to 2007 in
      Tottori University Hospital, were included in this study. One hundred seventy
      four patients underwent endometrial curettage or Pipelle biopsy preoperatively.
      Histological grade was compared between preoperation and postoperation. Magnetic
      resonance imaging (MRI) was performed before surgery, and the depth of MI was
      assessed as 3 levels (no MI, <50%, and >50%). During surgery, the uterine wall
      was incised at the most invasive part, and then, intraoperative gross assessment
      was evaluated as less than or greater than 50%. RESULTS: Histological evaluation
      revealed that 34 patients had no invasion, 97 had less than 50% MI, and 60 had
      greater than 50% MI. On MRI assessment, 135 patients had correct diagnoses, and
      the accuracy was 70.7%. Regarding the diagnosis of greater than 50% MI depth, the
      accuracy, the sensitivity, and the specificity of the MRI assessment were 83.2%,
      75.0%, and 85.7%, respectively. Seventeen patients were overestimated, and 15
      patients were underestimated by the MRI assessment. On intraoperative gross
      assessment, 162 patients had correct diagnoses, 8 patients were overestimated,
      and the remaining 21 patients were underestimated. The accuracy of the gross
      assessment was 84.8%, the sensitivity was 65.0%, and the specificity was 93.9%.
      The preoperative grading accuracy was 71.8% (125/174). A discrepancy between
      preoperative and postoperative grades was more frequent in a low-grade tumor. The
      incidence of underdiagnosis was significantly higher in patients with a grade 3
      (G3) tumor than in those with a G1 or G2 tumor in both assessments. CONCLUSIONS:
      The present study suggests that gross assessment may be useful to determine MI of
      less than 50%, although patients with a G3 tumor were more frequently
      underestimated.

PMID- 19574780
TI  - The first-line investigation of postmenopausal bleeding: transvaginal ultrasound
      scanning and endometrial biopsy may be enough.
AB  - Postmenopausal bleeding is a common problem in clinical practice with significant
      implications; however, the diagnostic strategies often vary among different
      centers. In the recent years, there was a trend to adopt less invasive procedures
      without compromising efficacy and safety. There is continuous debate about the
      different available modalities for investigation, and a large number of studies
      were conducted to define their roles. Some authors recommended that hysteroscopy
      should be the standard investigation procedure for women with postmenopausal
      bleeding. Nonetheless, there is a strong evidence to suggest that transvaginal
      ultrasound scanning, with or without endometrial biopsy, is a safe and more cost
      effective initial tool in investigating these women. This commentary highlights
      this important issue and discusses the role of these different modalities.

PMID- 19574779
TI  - Patterns of failure for conservatively managed surgical stage I uterine
      carcinosarcoma: implications for adjuvant therapy.
AB  - To evaluate patterns of failure and overall survival for patients with surgical
      stage I uterine carcinosarcoma managed conservatively without adjuvant therapy. A
      computerized database identified 27 patients whose conditions have been diagnosed
      with surgical stage I uterine carcinosarcoma from 1993 to 2002. Charts were
      abstracted for patient demographics, tumor characteristics, recurrence, and
      survival. Of 27 patients, 23(85%) did not receive adjuvant therapy after
      undergoing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
      pelvic and paraaortic lymphadenectomy. Five patients were stage IA, 14 were stage
      IB, and 4 were stage IC. Fourteen patients had either poorly differentiated
      endometrioid carcinoma alone or in combination with papillary serous carcinoma
      (61%) as their epithelial tumor component. The median nodal count was 9 (range, 3
      21). Eleven patients are alive without evidence of disease with a median follow
      up of 63 months (range, 12-164 months). Eleven patients had recurrence with a
      median time to recurrence of 13 months (range, 6-39 months), and all are dead of
      disease. Univariate analysis demonstrated that poorly differentiated epithelial
      or papillary serous histologic diagnosis was the only predictor variable
      associated with recurrence and, consequently, death (P = 0.04). Approximately 50%
      of patients with surgical stage I carcinosarcoma who are observed without
      adjuvant therapy will experience a recurrence. Because most patients will recur
      distantly, systemic chemotherapy should be considered for patients with early
      stage uterine carcinosarcoma.

PMID- 19574781
TI  - A 14-year-old female patient with FIGO stage IB endometrial carcinoma: a case
      report.
AB  - INTRODUCTION: This is the second report on the conservative treatment of
      endometrial carcinoma in a female patient younger than fifteen years. Case A, a
      14-year-old teenager, presented with menorrhagia. An endometrial biopsy revealed
      grade 2 endometrioid adenocarcinoma. The estrogen receptor and progesterone
      receptor were strongly positive in 60% and 90% of the tumor, respectively.
      Although she was administered medroxyprogesterone acetate for a month, it was not
      effective. She underwent standard surgery including a hysterectomy. She was
      thereafter free of disease 1 year after surgery. No estrogen receptor staining of
      the surgical specimen was observed, and 30% of the tumor was strongly positive
      for progesterone receptor. Direct DNA sequencing of exons 7 and 8 of PTEN and the
      K-ras codon 12 demonstrated the presence of no mutation. In addition, no dominant
      negative p53 mutation was found by a yeast functional assay. CONCLUSION: A
      uterine malignancy should therefore be included in the differential diagnosis in
      a young female patient complaining of abnormal genital bleeding.

PMID- 19574782
TI  - In vitro effects of hypoxia-inducible factor 1alpha on the biological
      characteristics of the SiHa uterine cervix cancer cell line.
AB  - INTRODUCTION: Hypoxia-inducible factor 1alpha (HIF-1alpha) regulates the
      transcription of many genes involved in key aspects of cancer biology. The aim of
      our study was to explore the effects of HIF-1alpha on the biological
      characteristics of the uterine cervix cancer (UCC) cell line SiHa, such as
      proliferation, apoptosis, and migration under normoxia and hypoxia. METHODS: Full
      length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF
      1alpha) were transfected into UCC SiHa cells. The expression of HIF-1alpha and
      its targets such as vascular endothelial growth factor (VEGF), CXC chemokine
      receptor 4 (CXCR4), and human growth and transformation-dependent protein (HGTD
      P) was detected by immunocytochemistry, Western blot, and semiquantitative
      reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis,
      and migration were surveyed by methyl thiazolyl tetrazolium assay, terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining, and
      scratching test. RESULTS: The expression of HIF-1alpha increased in fL HIF-1alpha
      but not in dn HIF-1alpha SiHa cells. Consistently, the expression of HIF-1alpha
      target genes such as VEGF, CXCR4, and HGTD-P increased in fL HIF-1alpha
      transfected SiHa cells but decreased in dn HIF-1alpha-transfected SiHa cells. The
      UCC cells transfected with fL HIF-1alpha had increased cellular proliferation and
      migration. However, the inhibition of HIF-1alpha through dn HIF-1alpha attenuated
      cell proliferation and migration under both normoxia and hypoxia. CONCLUSIONS:
      Hypoxia-inducible factor 1alpha affects the proliferation, apoptosis, and
      migration of UCC SiHa cells in part by regulating the expression of its target
      genes such as VEGF, HGTD-P, and CXCR4. Targeting HIF-1alpha may be a promising
      strategy for molecular therapy for UCC.

PMID- 19574783
TI  - Immunogenicity, reactogenicity, and safety of human papillomavirus 16/18 AS04
      adjuvanted vaccine in Japanese women: interim analysis of a phase II, double
      blind, randomized controlled trial at month 7.
AB  - A phase II, double-blind, controlled randomized multicenter study with human
      papillomavirus (HPV) 16/18 AS04 (3-O-desacyl-4'-monophosphoryl lipid A and
      aluminum hydroxide)-adjuvanted vaccine is ongoing in Japanese women aged 20 to 25
      years. An interim analysis was performed at month 7 (1 month after the third dose
      of vaccine) to determine reactogenicity, safety, and immunogenicity of the
      vaccine and to evaluate the baseline HPV-16/18 seropositivity and DNA status of
      women. In the HPV-16/18 group (according-to-protocol cohort for immunogenicity
      analysis), 100% seroconversion was observed against HPV-16 and HPV-18 at month 6
      (5 months after the second dose) and at month 7. At month 7, anti-HPV-16
      geometric mean titer (GMT) was 7441.0 enzyme-linked immunosorbent assay units/mL
      and anti-HPV-18 GMT was 3805.4 enzyme-linked immunosorbent assay units/mL, which
      is, respectively, 250- and 168-fold higher than GMTs observed after natural
      infection with HPV-16 or HPV-18. In the total vaccinated cohort, the
      seropositivity rates against HPV-16 and HPV-18 at study entry were 17.3% and
      15.8%, respectively. At the same time point, HPV-16 and HPV-18 DNA was detected
      in 6.5% and 4.0% of the women, respectively. The immunogenicity of the HPV-16/18
      vaccine and the HPV prevalence before vaccination in Japanese women are in line
      with what was observed in other populations. Injection site symptoms and some
      general symptoms were reported more frequently in the HPV-16/18 group than in the
      hepatitis A vaccine group but had no impact on compliance with completion of the
      vaccination course. Overall, the HPV-16/18 vaccine had a good safety profile, was
      well tolerated, and is highly immunogenic in the study population of Japanese
      women.

PMID- 19574784
TI  - Patterns of failure and prognostic factor analyses in locally advanced cervical
      cancer patients staged by positron emission tomography and treated with curative
      intent.
AB  - PURPOSE: The aim of this retrospective analysis was to assess whether parameters
      derived from magnetic resonance imaging (MRI) and positron emission tomography
      (PET) provide incremental prognostic value compared with International Federation
      of Gynecology and Obstetrics (FIGO) stage in cervix cancer patients treated with
      curative intent using concurrent chemoradiotherapy. MATERIALS AND METHODS: This
      was a retrospective study of patients with locoregionally advanced cervical
      cancer staged by examination under anesthesia and pretreatment MRI and PET.
      Potential prognostic factors examined were derived from either clinical
      evaluation (age, FIGO stage, clinical diameter, histology), MRI (corpus invasion,
      tumor volume), or PET (lymph node metastasis). Outcome measures examined were
      overall survival, relapse-free survival, time to failure, local failure, nodal
      failure, and distant failure. RESULTS: There were 206 eligible patients. The mean
      potential follow-up was 4.4 years. At 5 years, for all patients, overall survival
      rate was 59%. For all outcome measures apart from local failure, for which
      adenocarcinoma histology was the most powerful adverse prognostic factor (HR,
      4.29; P < 0.0001), lymph node status on PET was the dominant unifactor and
      multifactor prognostic factor. Corpus involvement on MRI was significantly
      associated with nodal involvement on PET but of MRI-derived parameters only tumor
      volume has prognostic value, limited to time to failure and nodal failure.
      CONCLUSIONS: Nodal status on PET was the major predictor of outcome in locally
      advanced cervix cancer treated with chemoradiation and was superior to FIGO
      staging. Tumor volume measured from MRI appears to be an important predictor of
      loco-regional relapse.

PMID- 19574785
TI  - Distribution of human papillomavirus genotypes in archival cervical lesions in
      eastern inner Mongolian autonomous region, China.
AB  - INTRODUCTION: Human papillomavirus (HPV) is the main etiologic factor for
      cervical cancer (CC). To investigate the prevalence of HPV types in archival CC
      and its precursors collected form Tongliao area, which is located in the east of
      Inner Mongolian autonomous region, China, and compare the genotype distribution
      of HPV in cervical lesions between Han Chinese and Mongolian. METHODS: The
      infections of HPV in a total of 175 cases of formalin-fixed, paraffin-embedded
      samples, including 71 low-grade squamous intraepithelial lesions (LSIL), 27 high
      grade squamous intraepithelial lesions (HSIL), and 77 CC were detected by the
      combination of consensus primers nested polymerase chain reaction (PCR) and type
      specific primers nested PCR. RESULTS: Overall, HPV prevalence was 93.5% in CC,
      92.6% in HSIL, and 63.4% in LSIL. Human papillomavirus 16 was the most
      predominant HPV type in all cervical lesions, detected in 83.1% of CC, 77.8% of
      HSIL, and 33.8% of LSIL. Human papillomavirus 45 was the second most predominant
      HPV type in CC (16.9%) and HSIL (11.1%). Human papillomavirus 33 was the second
      most predominant HPV type in LSIL (8.5%). Human papillomavirus 18, equal with HPV
      45, was the second most common type in Mongolian CC (15.6%), whereas in Han
      Chinese specimens, no HPV 18 was found. CONCLUSIONS: The prevalence of HPV 45 in
      CC and HSIL in Tongliao area were relatively higher than other regions of China.
      Comparing the distribution of HPV types in Han Chinese and Mongolian, the
      prevalence of HPV 18 in CC from Mongolian was significantly higher than that in
      Han Chinese.

PMID- 19574786
TI  - Comparison of the hybrid capture II assay with the human papillomavirus DNA chip
      test for the detection of high-grade cervical lesions.
AB  - Cervical intraepithelial neoplasia (CIN) 2 is used as the threshold for treatment
      decisions. This study was conducted to evaluate the clinical efficacy of the
      Hybrid Capture II assay (HC2) and the human papillomavirus (HPV) DNA chip test
      (HDC) for detecting HPV in high-grade cervical lesions CIN2 or greater, including
      adenocarcinoma (CIN2+). Seven hundred forty-one women with abnormal cervical
      cytology were evaluated with the HC2, the HDC, and histological assessment of the
      cervix. The overall agreement of the 2 HPV tests was 88.8% (kappa value, 0.61).
      Of 615 high-risk HPV-positive specimens by the HC2, 571 (92.8%) were HDC
      positive. Both tests were performed similarly on CIN2+ samples; the sensitivities
      of the HC2 and HDC as predictors of CIN2+ were 93.4 and 92.6%, respectively. In
      83 cases of discrepancies between the HC2 and HDC, genotyping of 39 HC2
      negative/HDC-positive cases revealed 13 HPV-53, 8 HPV-58, 7 HPV-16, 6 HPV-18, 2
      HPV-68, 1 HPV-31, 1 HPV-45, and 1 HPV-66. In 515 patients with CIN2+, HPV-16
      (45.0%) was the most common type; the next most common types were HPV-58 (20.8%),
      HPV-18 (16.1%), HPV-31 (6.6%), and HPV-33 (6.6%). Human papillomavirus types 16,
      58, and 18 were more likely associated with CIN2+ (P < 0.05). In conclusion, the
      HDC is a reliable diagnostic tool for the detection of CIN2+. In addition, the
      HDC provides useful information regarding viral genotypes.

PMID- 19574787
TI  - A phase II trial of erlotinib in recurrent squamous cell carcinoma of the cervix:
      a Gynecologic Oncology Group Study.
AB  - OBJECTIVES: To determine the proportion of patients with tumor response, the
      proportion who survived progression-free for at least 6 months (progression-free
      survival >or= 6 months), and the frequency and severity of toxicities of patients
      with recurrent squamous cell carcinoma of the uterine cervix treated with
      erlotinib. METHODS: This was a multicenter, open-label, single-arm trial
      evaluating the toxicity and efficacy of oral erlotinib at an initial dosage of
      150 mg daily until progressive disease or adverse effects prohibited further
      therapy. RESULTS: Twenty-eight patients with squamous cell carcinoma were
      enrolled onto this trial. Twenty-five patients were evaluable. There were no
      objective responses, with 4 (16%) patients achieving stable disease; only 1
      patient had a progression-free survival of 6 months (4%) or more. The 1-sided 90%
      confidence interval for response was 0.0% to 8.8%. The 2-sided 90% confidence
      interval for the proportion of patients surviving progression-free for at least 6
      months is 0.2% to 17.6%. Erlotinib was well tolerated, with the most common drug
      related adverse events being gastrointestinal toxicities, fatigue, and rash.
      CONCLUSIONS: Erlotinib is inactive as monotherapy in patients with recurrent
      squamous cell carcinoma of the uterine cervix.

PMID- 19574789
TI  - Neoadjuvant paclitaxel and cisplatin in uterine cervical cancer: long-term
      results.
AB  - OBJECTIVES: To assess the effect of neoadjuvant chemotherapy with paclitaxel and
      cisplatin on long-term (5-year) survival of patients with stage IB2 to IIB
      cervical cancer. MATERIALS AND METHODS: Forty-three consecutive patients with
      International Federation of Gynecology and Obstetrics stage IB2 to IIB uterine
      cervical cancer were treated with intravenous paclitaxel (60 mg/m), followed by
      intravenous cisplatin (60 mg/m) every 10 days. Two weeks after the third cycle of
      chemotherapy, the patients underwent surgery or radiation therapy, depending on
      overall condition. They were followed up, and 5-year survival rates and factors
      affecting prognosis were evaluated. RESULTS: All of 43 patients underwent
      surgery. Of the 43 patients, 17 (39.5%) showed a complete response, 22 (51.2%)
      had a partial response to cisplatin-paclitaxel, making the overall response rate
      90.7%; the remaining 4 patients (9.3%) had a stable disease. A down-staging
      response was seen in 72.1% (31/43) of patients showing a response. After surgery,
      patients received adjuvant therapy according to their pathological findings.
      Among the 43 patients, 37 were followed up. Kaplan-Meier analysis showed that the
      overall 2- and 5-year survival rates were 94.5% and 89.2%, respectively. Initial
      stage, response to neoadjuvant chemotherapy, differentiation, depth of invasion
      after chemotherapy, and metastasis were significantly correlated with survival.
      Differences in TA4, tumor size, and stage before and after chemotherapy were also
      significantly correlated with survival. In contrast, initial tumor size,
      carcinoembryonic antigen concentration, cell type, and lymphovascular invasion
      did not correlate significantly with survival rate. CONCLUSIONS: Combination
      neoadjuvant chemotherapy with paclitaxel and cisplatin may improve long-term
      survival of patients with uterine cervical cancer.

PMID- 19574790
TI  - Disseminated tumor cells in bone marrow may affect prognosis of patients with
      gynecologic malignancies.
AB  - INTRODUCTION: The presence of disseminated tumor cells (DTC) in the bone marrow
      (BM) of breast cancer patients is associated with poor prognosis. Several studies
      demonstrated that tumor cell dissemination may occur in gynecologic cancer and
      affect clinical outcome. The aim of our study was to evaluate the incidence of
      DTC and to assess their prognostic significance in patients with gynecologic
      malignancies. METHODS: Bone marrow aspirates from 377 patients with primary
      ovarian (112), endometrial (141), cervical (102), and vulvar cancer (22)
      undergoing surgery at the Department of Gynecology and Obstetrics, University
      Hospital, Tuebingen, Germany between November 2001 and November 2007, were
      included into the study. Disseminated tumor cells were identified by
      immunocytochemistry using the pancytokeratin antibody A45B/B3 and by
      cytomorphology. RESULTS: Disseminated tumor cells were detected in 19% of BM
      aspirates from patients with gynecological malignancies. Incidences of DTC in
      ovarian, endometrial, cervical, and vulvar cancer were 25%, 16%, 19%, and 5%,
      respectively. For patients with ovarian and endometrial cancer, no correlation
      with established clinicopathological factors was observed. In case of cervical
      cancer, BM positivity was correlated with International Federation of Gynecology
      and Obstetrics stage, tumor size, and nodal involvement. Bone marrow positivity
      of ovarian cancer patients was correlated with significantly shorter disease-free
      survival (P = 0.035). For other tumor entities, no association between BM status
      and clinical outcome could be observed. CONCLUSIONS: We conclude that up to 25%
      of patients with loco-regionally restricted gynecologic malignancies present with
      DTC at the time of diagnosis. For ovarian cancer patients, BM status affected
      clinical outcome.

PMID- 19574788
TI  - Persistent high-risk human papillomavirus infections and other end-point markers
      of progressive cervical disease among women prospectively followed up in the New
      Independent States of the Former Soviet Union and the Latin American Screening
      study cohorts.
AB  - BACKGROUND: New end points are needed in future human papillomavirus (HPV)
      vaccine efficacy studies that accurately predict disease progression. OBJECTIVES:
      Potential intermediate end points were analyzed in the combined New Independent
      States of the Former Soviet Union (NIS) and the Latin American Screening (LAMS)
      study cohorts. STUDY DESIGN AND METHODS: Data files of 2 international screening
      trials, the NIS (n = 3187) and the LAMS (n = 12,114) study cohorts, were
      combined, and a subcohort of 1865 (n = 854 and n = 1011 for the NIS and the LAMS,
      respectively) women prospectively followed up for 19.7 (median, 22.2) months was
      analyzed for different intermediate end-point markers of disease progression to
      squamous intraepithelial lesion (SIL), cervical intraepithelial neoplasia grade 1
      and higher (CIN1+), and CIN grade 2 and higher (CIN2+) as terminal events.
      RESULTS: : Altogether, 131 (7.0%), 90 (4.8%), and 39 (2.1%) cases progressed to
      SIL, CIN1+, and CIN2+, respectively, progression times being equal in the NIS
      (11.9, 16.8, and 19.6 months) and LAMS (13.6, 14.1, and 15.4 months) cohorts (P =
      0.931, P = 0.335, and P = 0.535). The 2 most powerful end-point markers of
      disease progression to CIN2+ were high-grade squamous intraepithelial lesions
      based on Papanicolaou test results at 6-month (odds ratio [OR] = 47.1; 95%
      confidence interval [CI], 17.3-128.7) and 12-month (OR = 21.5; 95% CI, 5.1-90.8)
      follow-up visits, with longitudinal positive and negative predictive values of
      42.1% and 98.0% (6 months) and 33.3% and 97.7% (12 months). Of the virological
      end points, more than 6 months of persistent high-risk HPV (HR-HPV) was the most
      powerful predictor of progression to CIN1+ (OR = 18.6; 95% CI, 2.5-136.5), with
      longitudinal positive and negative predictive values of 10.3% and 99.4%,
      respectively. No additional benefit was obtained using more than 12 months of
      persistent HR-HPV end point. CONCLUSIONS: High-grade squamous intraepithelial
      lesion based on a Papanicolaou test results at 6- or 12-month follow-up visits
      was the most powerful end point, either considering cytological end points alone
      or in comparison to any of the virological end points. Of the virological end
      points, more than 6-month HR-HPV persistence criteria give the most powerful
      estimate of a progressive disease.

PMID- 19574791
TI  - Quality of life and sexual, bladder, and intestinal dysfunctions after class III
      nerve-sparing and class II radical hysterectomies: a questionnaire-based study.
AB  - BACKGROUND: To compare quality of life and bladder, intestinal, and sexual
      dysfunctions in 2 groups of patients undergoing different types of radical
      hysterectomies (RHs). METHODS: Patients with cervical cancer who underwent RH
      have been enrolled in a questionnaire-based study. Quality of life (QoL) and
      bladder, intestinal, and sexual dysfunctions were evaluated with the Functional
      Assessment of Cancer Therapy-Cervix (FACT-Cx). Patients were grouped according to
      the type of RH: group 1, class II RH and group 2, class III nerve-sparing RH
      (NSRH). RESULTS: Of 157 women included in the study, 127 filled out the
      questionnaire. Overall, QoL score assessed with the FACT questionnaire did not
      differ significantly between the 2 groups. The FACT subscales assessing physical,
      functional, emotional, and social well-being did not differ significantly between
      the 2 groups, whereas the FACT-Cx subscales assessing disease-related symptoms in
      group 2 patients showed a significantly worse score (72 vs 66; P = 0.03).
      Evaluating singularly the 15 items of the Cx subscales assessing disease-related
      symptoms, we did not find any significant difference between the 2 groups, but
      only Cx1 ("I am bothered by discharge or bleeding from my vagina") was
      significantly worse in group 2 patients. At univariate analysis, we found that
      NSRH and adjuvant radiotherapy (RT) impact negatively on the FACT-Cx subscales
      regarding pelvic visceral function. However, at multivariate analysis, only
      adjuvant RT impact negatively. CONCLUSIONS: Patients submitted to class III NSRH
      did not present worse QoL and pelvic visceral dysfunctions when compared with
      class II RH. The RT seems to be a factor impacting negatively on bladder and
      sexual function.

PMID- 19574792
TI  - Intestinal complications after pelvic exenterations in gynecologic oncology.
AB  - OBJECTIVES AND METHODS: The present study reviews the frequency of intestinal
      complications in patients having undergone pelvic exenteration in our department
      between July 1999 and June 2008. RESULTS: Ninety patients with pelvic
      exenteration were included. R0 resection was achieved in 61 patients (67.8%), R1
      in 20 patients (22.2%), and R2 in 9 patients (10.0%). Sixty-four patients had a
      rectal resection, all less than 7 cm from the anal verge. Forty-two of them had a
      rectal anastomosis; in 23 cases, with a protective colostomy. The other 22
      patients had a terminal colostomy. Fifty-three patients had an ileal anastomosis
      for bladder reconstruction by ileal conduit, and 29 patients had an ileo
      ascendostomy for an ileocecal pouch.Twenty-three patients (25.6%) needed surgical
      intervention for complications; anastomotic dehiscence being most frequent with 7
      cases (7.8%). Three leakages appeared in ileal anastomoses (3/53, 5.7%) and 4 in
      rectal anastomoses (4/42, 9.5%). Although not significantly, the risk of
      symptomatic leakage was lower for patients with a protective colostomy (1/23,
      4.3%) than for those without (3/19, 15.7%). We found no correlation between the
      preceding radiotherapy or chemotherapy and the frequency of breakdown of rectal
      anastomosis. CONCLUSIONS: The risk of intestinal complications in exenterative
      surgery is moderate and not higher than in surgery for rectal cancer. Clinical
      appearance and, hence, relevance of anastomotic leakage may be reduced by a
      temporary diverting stoma.

PMID- 19574793
TI  - Complications of laparoscopic radical hysterectomy and pelvic lymphadenectomy-
      experience of 117 patients.
AB  - OBJECTIVE: To describe the combined surgical technique of laparoscopic radical
      hysterectomy and pelvic lymphadenectomy (LRH + LPL) for cervical cancers and
      summarize our experiences in prevention and treatment of complications, so as to
      provide strategies to prevent and appropriately manage the complications that may
      occur during these procedures. METHODS: A retrospective study was conducted on
      LRH + LPL in 117 cases of cervical cancer with International Federation of
      Gynecology and Obstetrics stages Ib (n = 96) and II a (n = 21) from August 1998
      to December 2006. The intraoperative and postoperative complications were
      analyzed. RESULTS: The overall conversion rate was 1.7% (2/117). Four patients
      had vessel injuries, 3 of which were treated laparoscopically. One patient had a
      common iliac vein laceration that could not be controlled laparoscopically after
      failing to deal with the injured branch of common iliac vein. Cystotomy occurred
      in 5 patients. One case of stage IIa with a bladder laceration longer than 3 cm
      was converted to laparotomy during the early stages of the learning curve. The
      remaining 4 were managed laparoscopically. Postoperative complications occurred
      in 38.5% (n = 45) of the patients, including 38 patients with urinary retention
      who exhibited complete resolution within 6 months by intermittent training and
      catheterization, 4 with lymphocyst who underwent conservation treatment, 1 with
      ureteral fistula that was treated by cystoscopic placement of double-J ureteral
      stents, 1 with mild adynamic bowel obstruction who received conservative
      management, and 1 with vesicovaginal fistula that was closed by conservative
      treatment. CONCLUSIONS: With the continuous skilled laparoscopic technology,
      mastering the tips of prevention, and treatment of complications, LRH + LPL will
      be widely performed in the future.

PMID- 19574794
TI  - Modified posterior pelvic exenteration for ovarian cancer.
AB  - INTRODUCTION: A modified posterior pelvic exenteration (MPE) might be needed to
      reach an optimal tumoral reduction. The issue of this study is to relate a
      multicentric experience of this kind of resection. MATERIALS: Three hundred five
      patients who needed an MPE were analyzed from 9 French cancer centers. One
      hundred sixty-eight MPEs were performed during initial surgery (55.1%), 69 during
      interval surgery (22.6%), 36 after chemotherapy (11.8%), and 32 for recurrences
      (10.5%). RESULTS: Three hundred two colorectal anastomoses were realized with a
      protective stoma in 59 (19.5%) of cases and a stoma closure in 76.5% (51). The
      rate of functional anastomosis was 96% (290/302). Complications occurred in 26.9%
      (82/305) of the patients, with a fistula in 25 (8.2%). The reintervention rate
      was 8.8% (27/305). The median length of hospitalization was 15 days. The absence
      of a macroscopic residual disease was obtained in 58% (173/303) of cases. A
      residual disease that was 1 cm or smaller was observed in 73 cases (24%) and 2 cm
      or smaller observed in 36 (11.9%). Postoperative chemotherapy was started with a
      median time of 32 days.Postoperative death occurred in 1 patient (0.33%). The
      survival rates were 62.7% and 27.6% at 2 and 5 years, respectively. With a
      multivariate analysis, the 2 significant prognostic factors were residual disease
      and time of surgery (P < 0.0001). CONCLUSIONS: A rectal invasion should not be an
      obstacle to reach the aim to obtain a macroscopic minimal residual disease or, if
      possible, the absence of one. An MPE is useful in those cases to reach optimal
      cytoreduction, with comparable results whatever the patient's age is. A temporary
      protective stoma should be considered only exceptionally.

PMID- 19574795
TI  - Exenterations 60 years after first description: results of a survey among US and
      German Gynecologic Oncology Centers.
AB  - OBJECTIVE: Sixty years after exenterative surgery was introduced into gynecologic
      oncology, the indications and contraindications, techniques, and adjuvant
      therapies after exenteration are controversially discussed between gynecologic
      oncologists. METHODS: To evaluate the current patterns of care, a questionnaire
      with 48 items was sent to 40 Society of Gynecologic Oncologists member clinics
      with fellowship programs and all 38 German teaching hospitals for gynecologic
      oncology. RESULTS: The mean number of exenterations performed during the last 5
      years was comparable in both countries. Consistently, (central) recurrent
      cervical cancer or persistent tumor after chemoradiation is the main indication.
      Before exenteration, positron emission tomography-computed tomography is mostly
      performed in the United States, whereas magnetic resonance imaging is the
      preferred imaging tool in Germany. Staging is more often done surgically in the
      United States (61%) compared with Germany (32%). None of the US institutions
      recommend an exenteration for patients with International Federation of
      Gynecology and Obstetrics stage IVA in contrast to 43% in Germany. In the case of
      fistula to the bladder and/or rectum, exenteration was recommended only by 29%
      and 61% in US and German clinics, respectively. In Germany, interdisciplinarity
      with general surgeons, urologists, plastic surgeons, and radio-oncologists is
      more common. There is consensus to apply adjuvant therapy after exenteration in
      patients with positive margins and/or positive lymph nodes. However, adjuvant
      therapy is more frequently recommended in Germany (93%) than in the United States
      (74%). CONCLUSIONS: Our data reflect considerable differences about indications
      and contraindications, preoperative staging, and adjuvant therapy for pelvic
      exenteration between Germany and the United States.

PMID- 19574796
TI  - The value of ureteric stents in debulking surgery for disseminated ovarian
      cancer.
AB  - OBJECTIVES: To review the value of ureteric catheterization in extensive
      debulking surgery in women with disseminated ovarian cancer. METHODS: Our
      database was searched for all women who had a laparotomy for advanced stage
      (stages III and IV) ovarian cancer between January 2001 and December 2007. Women
      who had the word(s) "ureteric," "ureter," "stent," "stents," and "stented" either
      in their operation notes or the multidisciplinary meeting discussions were
      filtered to identify those who had a ureteric stent inserted. Stents inserted
      because of excision/injury to ureters with reanastomosis or reinsertion to
      bladder were excluded. RESULTS: Fourteen out of 442 patients were identified as
      having a "prophylactic" stent inserted. The mean age of this series of 14 women
      was 66.6 years. Seven women had ultraradical surgery requiring bowel resection
      and/or resection of tumor from the bladder. Nine women had a stent inserted
      because of the presence of a hydroureter, 3 for ureteric stricture and 2 to
      protect a flimsy or fragile ureter after ureteric dissection and tumor debulking.
      There were no ureteric complications during the post-operative period. This
      resulted in 9 (64%) women achieving either complete or optimal cytoreduction of
      their tumor bulk. Optimal/complete cytoreduction in all stage III/IV cases during
      this period was 88%. CONCLUSIONS: Ureteric silastic stents are relatively easy to
      insert and pose few immediate and long-term problems. They should be considered
      in women after extensive pelvic side-wall debulking in an attempt to reduce the
      risk of postoperative ureteric complications.

PMID- 19574797
TI  - Vaginal restoration in survivors of childhood rhabdomyosarcoma.
AB  - Childhood genital rhabdomyosarcoma is a devastating diagnosis. Treatment is
      usually rigorous, comprising extensive surgery often with adjuvant chemotherapy
      and radiotherapy. This management is, however, increasingly successful, and
      survival into adolescent and adult life is becoming more commonplace. These young
      women will have sexual and reproductive expectations similar to those of their
      peers and will present to gynecologists for advice and treatment. This report
      describes the presenting problems seen in this group and highlights the complex
      nature of the investigations required and the treatments available.

PMID- 19574798
TI  - Actinomycin d versus methotrexate-folinic acid as the treatment of stage I, low
      risk gestational trophoblastic neoplasia: a randomized controlled trial.
AB  - This study is to compare the remission and complication rates of actinomycin D
      (Act-D) and methotrexate-folinic acid (MTX-FA) as single-agent treatments of
      stage I, low-risk gestational trophoblastic neoplasia (GTN). From 1994 to 2005,
      all women with International Federation of Gynecology and Obstetrics stage I, low
      risk GTN were randomly assigned to received either intravenous Act-D 10 microg/kg
      per day for 5 days every 2 weeks or intramuscular methotrexate 1 mg/kg per day on
      days 1, 3, 5, and 7 with intramuscular folinic acid 0.1 mg/kg per day on days 2,
      4, 6, and 8 every 2 weeks. Forty-nine women met the eligibility criteria. Age,
      human chorionic gonadotropin level, and International Federation of Gynecology
      and Obstetrics score were similar in both treatment groups. Of the 22 women who
      received Act-D, 2 were lost to follow-up. Among the 27 women who received MTX-FA,
      2 were lost to follow-up, and 6 had to switch to Act-D because of the rising
      levels of liver enzymes. All 20 women (100%) in the Act-D arm achieved remission
      compared with 14 (73.6%) in 19 women in the MTX-FA arm (P = 0.02). Mucositis and
      alopecia were reported more frequently in the Act-D group, whereas elevations of
      liver enzyme levels were more frequent in the MTX-FA group. Actinomycin D seems
      to be more effective than MTX-FA in the treatment of stage I, low-risk GTN.
      Larger multicenter randomized controlled trials should be conducted to establish
      the most appropriate regimen for these patients.

PMID- 19574799
TI  - Endometrial stromal sarcoma: treatment and patterns of recurrence.

PMID- 19574801
TI  - Ruptured aneurysm at the perforating artery supplying the insula: case report.
AB  - OBJECTIVE: Aneurysms originating from perforating branches of the middle cerebral
      artery are quite rare. Most of them arise from the lenticulostriate arteries,
      frequently located within the basal ganglia. We report a perforating artery
      aneurysm that was entirely embedded within the limen insulae. CLINICAL
      PRESENTATION: A 41-year-old man presented with an insular hematoma without
      subarachnoid hemorrhage caused by rupture of a small aneurysm on a perforating
      artery of the proximal middle cerebral artery supplying the insula. INTERVENTION:
      This rare aneurysm was resected via the transsylvian-insular approach.
      CONCLUSION: Although very rare, perforating artery aneurysms should be considered
      in young or middle-aged patients with an atypical intracerebral hematoma. This
      report discusses radiological and surgical characteristics of this unusual
      aneurysm.

PMID- 19574802
TI  - Acute confusional syndrome from a dural arteriovenous fistula.
AB  - OBJECTIVE: We describe a case of an acute confusional state associated with a
      right parietal dural arteriovenous fistula. CLINICAL PRESENTATION: A 67-year-old
      man in his usual state of health experienced an acute confusion episode preceded
      by a valsalva maneuver. The episode lasted approximately 60 minutes. Afterward he
      was able to remember everything that occurred. A magnetic resonance imaging scan
      suggested a right parietal dural arteriovenous fistula, which was confirmed by
      angiography. A seizure was ruled out by clinical examination and an
      electroencephalogram. INTERVENTION: The patient underwent therapeutic
      embolization and surgical ligation of the fistula. Feeding vessels to the
      malformation were cauterized within the leaves of the falx, and the draining vein
      was clipped with a titanium aneurysm clip and divided. An intraoperative
      angiogram was then performed, which showed obliteration of the fistula. There was
      no demonstrable confusion or memory loss noted postoperatively. CONCLUSION: We
      propose that venous hypertension from the dural arteriovenous fistula in
      combination with a valsalva maneuver caused ischemia in the right parietal lobe,
      eliciting a deficit in attention.

PMID- 19574803
TI  - Thorotrast-induced primary cerebral angiosarcoma: case report.
AB  - OBJECTIVE: Thorotrast was used as a contrast medium in clinical practice until
      the 1960s for outlining cerebral abscess cavities and ventricular cavities, and
      for angiography. Gliosarcomas, meningiomas, and schwannomas have been reported
      previously, as has Thorotrast-associated angiosarcoma, typically in the liver. A
      unique case of a primary intracerebral well-differentiated angiosarcoma in a 68
      year-old man with a history of colocalized exposure to Thorotrast is described.
      This may be the first case of a primary angiosarcoma in the brain. CLINICAL
      PRESENTATION: The patient presented with a progressive left-sided weakness 62
      years after initial surgery for a right parietal cerebral abscess, which included
      the instillation of Thorotrast into the abscess cavity. Computed tomography
      showed a right parietal tumor. INTERVENTION: An explorative craniotomy showed an
      intrinsic, infiltrating, very vascular tumor with surrounding calcification. The
      tumor appeared to arise from a benign cavernous vasoformative lesion intimately
      associated with a Thorotrast-type granuloma. The patient declined further surgery
      or radiotherapy. CONCLUSION: The histology, confirmation of radioactivity of the
      material obtained from within the tumor, and latency period of presentation
      provide compelling support for tumor induction by the Thorotrast. Primary lesions
      of the central nervous system associated with Thorotrast are very rarely
      reported, despite its extensive use in cerebral angiography and management of
      brain abscess between 1930 and 1960.

PMID- 19574804
TI  - A cylindrical extracranial cranial base neurinoma of the hypoglossal nerve: a
      rare tumor with a rare localization: case report.
AB  - OBJECTIVE: Neurinomas of the hypoglossal nerve are very rare. They are mostly
      located intracranially or combined intra- and extracranially, resulting in the so
      called dumbbell shape. The isolated extracranial localization of the neurinoma of
      the hypoglossal nerve adjacent to the cranial base as described in this case
      report is extremely rare. CLINICAL PRESENTATION: The 23-year-old patient
      presented with recurring headaches. She had right-sided hypoglossal nerve palsy
      for approximately 5 to 6 years. Magnetic resonance imaging revealed an
      extracranial tumor with contact to the cranial base originating from the
      hypoglossal nerve. INTERVENTION: The tumor was extirpated surgically and verified
      histologically as a schwannoma of the hypoglossal nerve. CONCLUSION: Pathologies
      of the hypoglossal nerve as such are very rare within the clinical landscape.
      When a tumor occurs, its shape and location must be analyzed to establish
      whether, or by which approach, surgical removal is feasible. Although very
      unusual, the mere extracranial occurrence of a hypoglossal neurinoma at the
      cranial base should be considered a differential diagnosis.

PMID- 19574805
TI  - Endoscopic intraventricular biopsy of infundibular Langerhans cell histiocytosis:
      case report.
AB  - OBJECTIVE: Surgical biopsy of isolated infundibular lesions is indicated in
      patients who are symptomatic or whose imaging suggests a treatable lesion. Early
      therapy can prevent irreversible neurological or endocrinological damage and,
      potentially, metastasis. These considerations justify the small risk associated
      with surgery. CLINICAL PRESENTATION: A 5-year-old boy presented with diabetes
      insipidus and an enhancing lesion of the pituitary stalk without evidence of
      extracranial disease. INTERVENTION: The lesion was biopsied via an endoscopic
      intraventricular approach without complications. Pathological examination
      revealed Langerhans cell histiocytosis. CONCLUSION: Endoscopic intraventricular
      biopsy can be considered as a less invasive alternative to craniotomy in patients
      with infundibular lesions protruding superiorly into the third ventricle.

PMID- 19574806
TI  - Transverse dorsal arachnoid web and syringomyelia: case report.
AB  - OBJECTIVE: We present a case of syringomyelia attributed to a transverse thoracic
      arachnoid web at T4. The cerebrospinal fluid pressure caudal to the web was
      higher than the cerebrospinal fluid pressure rostral to the web, causing a syrinx
      in the thoracic and cervical spinal cord above the web. CLINICAL PRESENTATION: A
      43-year-old man presented with numbness and a burning pain in his left upper back
      and extremities. Magnetic resonance imaging showed a cervical-thoracic syrinx
      that terminated relatively abruptly at T4. Because of the abrupt termination of
      the syrinx at T4 and the slight ventral displacement of the spinal cord at this
      level, a dorsal arachnoid web was suspected. INTERVENTION: A T4 laminectomy was
      performed. Intraoperative ultrasound before opening of the thecal sac showed a
      pulsating transverse dorsal arachnoid web. The dura was opened and the web
      resected, thus widely communicating the dorsal subarachnoid space. The syrinx
      dramatically decreased in size and the patient's pain improved but did not
      resolve completely. CONCLUSION: In patients with presumed idiopathic
      syringomyelia, imaging studies should be closely inspected for the presence of a
      transverse arachnoid web. Surgical resection of a transverse thoracic arachnoid
      web with syringomyelia can result in resolution of the syringomyelia and
      improvement in neurological function. Syrinx formation in patients with these
      webs may occur in the area of the spinal cord where there is lower cerebrospinal
      fluid pressure, which may be either rostral or caudal to the arachnoid web. We
      evaluate this hypothesis by comparing our case with other published cases.

PMID- 19574808
TI  - From bench to the operating room: a tale of the omnidirectional mirror fiber.

PMID- 19574820
TI  - Aurora Borealis (1865) by Frederic Edwin Church (1826-1900).

PMID- 19574821
TI  - Cavernous malformations of the basal ganglia and thalamus.
AB  - Cavernous malformations of the basal ganglia and thalamus present a unique
      therapeutic challenge to the neurosurgeon given their unclear natural history,
      the risk of surgical treatment, and the unproven efficacy of radiosurgical
      therapy. Via a PubMed search of the English and French literature, we have
      systematically reviewed the natural history and surgical and radiosurgical
      management of these lesions reported through April 2008. Including rates cited
      for "deep" cavernous malformations, annual bleeding rates for these lesions
      varied from 2.8% to 4.1% in the natural history studies. Across surgical series
      providing postoperative or long-term outcome data on 103 patients, we found an
      89% resection rate, a 10% risk of long-term surgical morbidity, and a 1.9% risk
      of surgical mortality. The decrease in hemorrhage risk reported 2 years after
      radiosurgery might be a result of natural hemorrhage clustering, underscoring the
      unproven efficacy of this therapeutic modality. Given the compounded risks of
      radiation-induced injury and post-radiosurgical rebleeding, radiosurgery at
      modest dosimetry (12-14 Gy marginal doses) is only an option for patients with
      surgically inaccessible, aggressive lesions.

PMID- 19574822
TI  - Developmental venous anomalies: current concepts and implications for management.
AB  - Developmental venous anomalies (DVAs), formerly known as venous angiomas, have
      become the most frequently diagnosed intracranial vascular malformation. DVAs are
      currently considered congenital cerebrovascular anomalies with mature venous
      walls that lack arterial or capillary elements. They are composed of radially
      arranged medullary veins, which converge in an enlarged transcortical or
      subependymal collector vein, and have characteristic appearances (caput medusae)
      on magnetic resonance imaging and angiography. DVAs were once thought to be rare
      lesions with substantial potential for intracerebral hemorrhage and considerable
      morbidity. The prevalence of incidental and asymptomatic DVAs has been more
      apparent since the advent of magnetic resonance imaging; recent cohort studies
      have challenged the once-held view of isolated DVAs as the cause of major
      neurological complications. The previously reported high incidence of
      intracerebral hemorrhage associated with DVAs is currently attributed to
      coexistent, angiographically occult cavernous malformations. Some patients may
      still have noteworthy neurological morbidity or die as a result of acute
      infarction or hemorrhage directly attributed to DVA thrombosis. DVAs can coexist
      with cavernous malformations and arteriovenous malformations. Such combination or
      transitional forms of malformations might suggest common pathways in
      pathogenesis. Recent data support a key role for DVAs in the pathogenesis of
      mixed vascular malformations.

PMID- 19574823
TI  - Seizure characteristics and control after microsurgical resection of
      supratentorial cerebral cavernous malformations.
AB  - OBJECTIVE: The optimal management of seizures associated with cerebral cavernous
      malformations (CCMs) is unclear. The aim of this study was to determine the
      efficacy of surgery in the management of CCM-associated seizures. METHODS: We
      conducted a retrospective review with follow-up of 164 patients who underwent
      microsurgical resection of supratentorial CCMs. Clinical and radiographic data
      were collected and then analyzed to determine predictors of developing epilepsy
      and predictors of postoperative seizure control after microsurgical resection.
      RESULTS: Of the patients, 61.5% presented with seizures, and 34.7% had clinically
      defined epilepsy. The development of epilepsy was associated with CCMs located in
      the temporal lobe and the absence of symptomatic hemorrhage. After microsurgical
      resection in 44 patients with intractable epilepsy, 72.7% were completely seizure
      free (Engel class 1), 11.4% had rare seizures (Engel class 2), 4.5% had
      meaningful improvement (Engel class 3), and 11.4% had no improvement (Engel class
      4). Predictors of complete seizure freedom were gross total resection, smaller
      CCMs, and the absence of secondary generalized seizures (94% of patients were
      seizure-free with all 3 predictors). CONCLUSION: Surgery is a safe and effective
      treatment for seizures associated with CCMs.

PMID- 19574824
TI  - Lateral supraorbital approach applied to olfactory groove meningiomas: experience
      with 66 consecutive patients.
AB  - OBJECTIVE: The lateral supraorbital approach for safely and completely removing
      olfactory groove meningiomas was assessed. METHODS: Between September 1997 and
      June 2008, a total of 656 meningiomas were operated on by the senior author (JH)
      at the Department of Neurosurgery, Helsinki University Central Hospital; 66 were
      olfactory meningiomas. We retrospectively analyze the clinical data, radiological
      findings, surgical treatment, histology, and outcome of all the olfactory groove
      meningioma patients and discuss the operative techniques used. RESULTS: Sixty-six
      patients were operated on by the lateral supraorbital approach. The median
      preoperative Karnofsky Performance Scale score was 80 (range, 40-100). Three
      patients were redo cases in which the primary operation had been performed
      elsewhere. Seemingly complete tumor removal was achieved in 60 patients (91%);
      there was no surgical mortality. Postoperatively, 6 patients (9%) had
      cerebrospinal fluid leakage, 5 (8%) had new visual deficits, 4 (6%) had wound
      infections, 4 (6%) had cotton granulomas, and 1 (2%) had a postoperative
      hematoma. The median Karnofsky score at discharge was 80 (range, 40-100). Six
      patients had recurrent tumors; 3 underwent reoperations after an average of 21
      months (range, 1-41 months); 1 was treated with radiosurgery, and 2 were only
      followed. During the median follow-up time of 45 months (range, 2-128 months),
      there were 4 recurrences (6%) diagnosed on average 32 months (range, 17-59
      months) after surgery. CONCLUSION: The lateral supraorbital approach can be used
      safely for olfactory groove meningiomas of all sizes with no mortality and
      relatively low morbidity. Surgical results and tumor recurrence with this fast
      and simple approach are similar to those obtained with more extensive, complex,
      and time-consuming approaches.

PMID- 19574825
TI  - Transsphenoidal decompression of the sellar floor for cavernous sinus
      meningiomas: experience with 21 patients.
AB  - OBJECTIVE: The aim of this study was to assess the outcome of cranial nerve and
      endocrine function after transsphenoidal decompression for symptomatic cavernous
      sinus (CS) meningioma. METHODS: Between 1991 and 2007, 21 patients (19 women and
      2 men; mean age, 51.1 +/- 10.6 years) harboring symptomatic CS meningiomas
      underwent transsphenoidal decompression. Sufficient bone removal, opening of the
      inferomedial wall of the CS, and tumor debulking were performed. RESULTS:
      Notably, the grading of preoperative optomotoric paresis improved in 15 of the 17
      patients who presented with that symptom. Complete recovery could be achieved in
      8 patients. Complete recovery rates in patients with preoperative grading of
      "good," "fair," and "poor" were 77.7%, 20%, and 0%, respectively (P = 0.0088).
      Improvement of cranial nerve dysfunction was found in 32 of 34 deficits. No
      worsening of cranial nerve function occurred. Endocrinologically, the prolactin
      level was normalized in 13 of the 17 patients with preoperative
      hyperprolactinemia. Recovery of growth hormone deficiency and hypogonadism were
      found in 3 patients (37.5%) and 1 patient (33.3%), respectively. Seventeen
      patients were followed for more than 3 years. Of these 17 patients, 12 patients
      received initial postoperative adjuvant radiotherapy. The overall tumor control
      rate after surgery with initial adjuvant radiotherapy was 100% (median follow-up,
      65 months; range, 36-126 months). CONCLUSION: Transsphenoidal decompression is a
      safe and effective treatment to improve cranial nerve and endocrine dysfunction
      in patients with symptomatic CS meningiomas. The less severe optomotoric nerve
      palsy before surgery, the better the chance of complete recovery of its function.
      Combined with adjuvant radiotherapy, this minimally invasive management also
      provided excellent long-term tumor control.

PMID- 19574826
TI  - Transsphenoidal pituitary macroadenomas resection guided by PoleStar N20 low
      field intraoperative magnetic resonance imaging: comparison with early
      postoperative high-field magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the applicability of low-field intraoperative magnetic
      resonance imaging (iMRI) during transsphenoidal surgery of pituitary
      macroadenomas. METHODS: Fifty-five transsphenoidal surgeries were performed for
      macroadenomas (modified Hardy's Grade II-IV) resections. All of the surgical
      processes were guided by real-time updated contrast T1-weighted coronal and
      sagittal images, which were acquired with 0.15 Tesla PoleStar N20 iMRI (Medtronic
      Navigation, Louisville, CO). The definitive benefits as well as major drawbacks
      of low-field iMRI in transsphenoidal surgery were assessed with respect to
      intraoperative imaging, tumor resection control, comparison with early
      postoperative high-field magnetic resonance imaging, and follow-up outcomes.
      RESULTS: Intraoperative imaging revealed residual tumor and guided extended tumor
      resection in 17 of 55 cases. As a result, the percentage of gross total removal
      of macroadenomas increased from 58.2% to 83.6%. The accuracy of imaging
      evaluation of low-field iMRI was 81.8%, compared with early postoperative high
      field MRI (Correlation coefficient, 0.677; P < 0.001). A significantly lower
      accuracy was identified with low-field iMRI in 6 cases with cavernous sinus
      invasion (33.3%) in contrast to the 87.8% found with other sites (Fisher's exact
      test, P < 0.001). CONCLUSION: The PoleStar N20 low-field iMRI navigation system
      is a promising tool for safe, minimally invasive, endonasal, transsphenoidal
      pituitary macroadenomas resection. It enables neurosurgeons to control the extent
      of tumor resection, particularly for suprasellar tumors, ensuring surgical
      accuracy and safety, and leading to a decreased likelihood of repeat surgeries.
      However, this technology is still not satisfying in estimating the amount of the
      parasellar residual tumor invading into cavernous sinus, given the false or
      uncertain images generated by low-field iMRI in this region, which are difficult
      to discriminate between tumor remnant and blood within the venous sinus.

PMID- 19574827
TI  - Intraoperative arachnoid and cerebrospinal fluid sampling in children with
      posterior fossa brain tumors.
AB  - OBJECTIVE: This study was conducted to determine whether arachnoid tissue or
      cerebrospinal fluid (CSF) sampling is valuable for risk stratification in
      children with posterior fossa brain tumors. METHODS: Arachnoid tissue and CSF
      from the cisterna magna (CSFCM) was sampled at the time of primary tumor
      resection. Results were compared with conventional staging methods (M stage) and
      correlated with patient outcome. RESULTS: Eighty-three patients were enrolled in
      the study. Arachnoid infiltration was identified in 11 of 80 (13.8%) and CSFCM
      was positive in 20 of 77 (26.0%) specimens. Arachnoid infiltration and CSF
      cytology were found in 20.0% and 44.8%, respectively, for
      medulloblastoma/pineoblastoma (primitive neuroectodermal tumor), 6.9% and 3.6%
      for pilocytic astrocytoma, and 0.0% and 33.3% for ependymoma. The 3-year event
      free survival (EFS) was negatively influenced by either arachnoid infiltration
      (40.9% arachnoid positive versus 65.4% arachnoid negative; P = 0.23) or CSFCM
      positivity (52.6% CSFCM positive versus 67.1% CSFCM negative; P = 0.03). The 3
      year EFS for patients with primitive neuroectodermal tumor who had positive
      arachnoid sampling was 33.3%, compared with 67.3% in patients who had no evidence
      of arachnoid infiltration (P = 0.26). The 3-year EFS for patients with primitive
      neuroectodermal tumor who had positive CSFCM was 50.0% compared with 67.5% in
      patients who had negative cytological analysis of CSFCM (P = 0.07). Arachnoid
      infiltration and CSF sampling were congruous with M stage in 73.3% and 86.2% of
      patients, respectively. CONCLUSION: Intraoperative evidence of arachnoid
      infiltration or CSFCM dissemination in patients with posterior fossa brain tumors
      occurs at a variable frequency that is dependent on tumor type, correlates with
      conventional M stage, and may be predictive of outcome.

PMID- 19574828
TI  - Stereotactic radiosurgical treatment of cranial and spinal hemangioblastomas.
AB  - OBJECTIVE: Stereotactic radiosurgery has been used for nearly 2 decades to treat
      hemangioblastomas, particularly those that are in surgically inaccessible
      locations or that are multiple, as is common in von Hippel-Lindau disease. There
      is a paucity of long-term published radiosurgical treatment outcomes,
      particularly for spinal lesions, in a large patient population. The purpose of
      this study was to provide a long-term retrospective evaluation of radiosurgical
      hemangioblastoma treatment effectiveness, with a special emphasis on the
      relatively recent use of frameless, image-guided radiosurgery in the treatment of
      spinal lesions. METHODS: From 1991 to 2007, 92 hemangioblastomas in 31 patients,
      26 with von Hippel-Lindau disease, were treated with radiosurgery (27 tumors
      treated with frame-based linear accelerator radiosurgery, and 67 tumors were
      treated with CyberKnife radiosurgery). The mean patient age was 41 years (range,
      18-81 years). The radiation dose to the tumor periphery averaged 23.4 Gy (range,
      12-40 Gy). The mean tumor volume was 1.8 cm (range, 0.058-65.4 cm). Tumor
      response was evaluated in serial, contrast-enhanced, computed tomographic, and
      magnetic resonance imaging scans. RESULTS: Clinical and radiographic follow-up
      data were available for 82 hemangioblastoma tumors. Only 13 (16%) of the treated
      hemangioblastomas progressed, whereas 18 tumors (22%) showed radiographic
      regression, and 51 tumors (62%) remained unchanged in size. With median follow-up
      of 69 months (range, 5-164 months), the actuarial local control rates at 36 and
      60 months were 85% and 82%, respectively. Radiosurgery improved lesion-associated
      symptoms in 36 of 41 tumors. During the follow-up period, 9 patients died of
      causes unrelated to the progression of their treated hemangioblastomas, and 5
      patients developed radiation necrosis. CONCLUSION: Stereotactic radiosurgery is
      safe and effective in the treatment of hemangioblastomas and is an attractive
      alternative to surgery for patients, including those with von Hippel-Lindau
      disease.

PMID- 19574829
TI  - Improvement of back pain with operative and nonoperative treatment in adults with
      scoliosis.
AB  - OBJECTIVE: The purpose of this study was to assess whether back pain is improved
      with surgical treatment compared with nonoperative management in adults with
      scoliosis. METHODS: This is a retrospective review of a prospective,
      multicentered database of adults with spinal deformity. At the time of enrollment
      and follow-up, patients completed standardized questionnaires, including the
      Oswestry Disability Index (ODI) and Scoliosis Research Society 22 questionnaire
      (SRS-22), and assessment of back pain using a numeric rating scale (NRS) score,
      with 0 and 10 corresponding to no and maximal pain, respectively. The initial
      plan for surgical or nonoperative treatment was made at the time of enrollment.
      RESULTS: Of 317 patients with back pain, 147 (46%) were managed surgically.
      Compared with patients managed nonoperatively, operative patients had higher
      baseline mean NRS scores for back pain (6.3 versus 4.8; P < 0.001), higher mean
      ODI scores (35 versus 26; P < 0.001), and lower mean SRS-22 scores (3.1 versus
      3.4; P < 0.001). At the time of the 2-year follow-up evaluation, nonoperatively
      managed patients did not have significant change in the NRS score for back pain
      (P = 0.9), ODI (P = 0.7), or SRS-22 (P = 0.9). In contrast, at the 2-year follow
      up evaluation, surgically treated patients had significant improvement in the
      mean NRS score for back pain (6.3 to 2.6; P < 0.001), ODI score (35 to 20; P <
      0.001), and SRS-22 score (3.1 to 3.8; P < 0.001). Compared with nonoperatively
      treated patients, at the time of the 2-year follow-up evaluation, operatively
      treated patients had a lower NRS score for back pain (P < 0.001) and ODI (P =
      0.001), and higher SRS-22 (P < 0.001). CONCLUSIONS: Despite having started with
      significantly greater back pain and disability and worse health status,
      surgically treated patients had significantly less back pain and disability and
      improved health status compared with nonoperatively treated patients at the time
      of the 2-year follow-up evaluation. Compared with nonoperative treatment, surgery
      can offer significant improvement of back pain for adults with scoliosis.

PMID- 19574830
TI  - Surgical results of the oblique paraspinal approach in upper lumbar disc
      herniation and thoracolumbar junction.
AB  - OBJECTIVE: This study was conducted to investigate the efficacy of treating
      central or paramedian disc herniations of the upper lumbar levels, including the
      thoracolumbar junction, through the oblique paraspinal approach. We published a
      technical case report on this subject in 2004. METHODS: Nineteen consecutive
      patients with intracanalicular disc herniations of the upper lumbar levels
      underwent the oblique paraspinal approach, which utilizes an operating
      microscope, from March 2005 through January 2008. Their clinical and radiological
      data were collected and analyzed. The patients were assessed with standard
      examinations preoperatively and evaluated with dynamic lumbar x-rays, 3
      dimensional computed tomographic scans, magnetic resonance imaging, standard pain
      and disability measurements, a visual analogue scale, the Oswestry disability
      index, and a patient satisfaction rate that checked their pain scores
      postoperatively. RESULTS: The average follow-up period was 28.1 months, with a
      maximum of 48 months. The visual analogue scale for back and leg pain and the
      Oswestry disability index, which recorded a preoperative mean of 6.7%, 7.2%, and
      64.7% and a postoperative mean of 3.2%, 3.0%, and 21.47%, respectively, showed
      statistically significant improvement at the time of the last follow-up
      evaluation, compared with preoperative scores. There have been neither recurrent
      disc herniations nor spinal instability during the follow-up period. CONCLUSION:
      In this study, 19 cases of intracanalicular disc herniations at the upper lumbar
      levels, including the thoracolumbar junction, were successfully excised with the
      oblique paraspinal approach without recurrence or instability. We found that the
      oblique paraspinal approach, which resulted in satisfactory clinical outcomes
      with few complications, could be one of the main surgical procedures used to
      treat intracanalicular disc herniations at the upper lumbar levels.

PMID- 19574831
TI  - Midterm outcome after microendoscopic decompressive laminotomy for lumbar spinal
      stenosis: 4-year prospective study.
AB  - OBJECTIVE: To evaluate the efficacy of radicular decompression in lumbar spinal
      stenosis using a microendoscopic technique. METHODS: This was a longitudinal
      prospective study of 50 patients with a diagnosis of lumbar spinal stenosis who
      were treated by microendoscopic decompression using an 18-mm METRx tubular
      retractor according to the METRx technique (Medtronic Sofamor Danek, Memphis,
      TN). Twenty of the patients had an additional disc prolapse, and a
      microendoscopic discectomy was associated with decompressive laminectomy. The
      results were evaluated using the visual analog scale pain score, Oswestry
      Disability Index score, patient satisfaction questionnaire, and modified Macnab
      classification. RESULTS: The average age of the patients was 56 years; 29 (58%)
      were men and 21 (42%) were women. The most commonly affected level was L4-L5
      (64%). The mean surgical intervention time was 94.3 (+/- 14.3) minutes. Mean
      postoperative hospital stay was 3.16 (+/- 2.3) days. The follow-up time after
      surgery was 4 years (48 +/- 6.6 months; range, 24-72 months). We obtained good or
      excellent results in 72% of patients, achieving good subjective satisfaction in
      68% of the patients. The mean decrease in the Oswestry Disability Index score was
      30.23 (+/- 24.29), the mean decrease in the leg pain visual analog scale score
      was 6.02 (+/- 2.57), and the mean decrease in the lumbar pain visual analog scale
      score was 0.84 (+/- 2.06). Adjusted mean differences were in all cases
      statistically significant (P < 0.05). CONCLUSION: Data indicate that, in our
      experience, on midterm follow-up, microendoscopic laminectomy decompression is an
      effective technique for the treatment of lumbar spinal stenosis.

PMID- 19574832
TI  - Analysis of complications in patients treated with the X-Stop Interspinous
      Process Decompression System: proposal for a novel anatomic scoring system for
      patient selection and review of the literature.
AB  - OBJECTIVE: The X-Stop Interspinous Process Decompression System (St. Francis
      Medical Technologies, Concord, CA) is an interspinous device used with increasing
      frequency in the treatment of degenerative lumbar spine conditions. To date,
      limited data are available on complications observed in association with X-Stop
      procedures, and even less information exists on their underlying causes. The aim
      of this study was to analyze a series of complications occurring at a single
      institution and their potential causes and propose an anatomic scoring system
      that may help to classify patients and prevent complications. METHODS: Sixty-nine
      patients were treated with the X-Stop. Forty-six single-level and 23 double-level
      operations (92 devices) were performed according to recommended indications. The
      mean follow-up duration was 23 months. RESULTS: Eight complications were
      recorded: 4 device dislocations and 4 spinous process (SP) fractures, including 2
      spontaneous fractures of the L4 SP in patients treated at L3-L4 and L4-L5. The
      following anatomic variants were demonstrated: markedly decreased interspinous
      distance (kissing spine-like), with concomitant facet joint hypertrophy, a
      posterior V-shaped interspinous area, limited accessibility of the space between
      the base and the tip of the SP because of facet joint hypertrophy and variations
      in the shape of the inferior surface of the cranial SP. CONCLUSION: This is the
      first study focusing on interspinous distractor complications and the anatomic
      features of the SP and interspinous areas of the patients, which could
      potentially be the underlying causes for those complications. The X-Stop can be
      an effective treatment option, but it is not a panacea for all patients with
      degenerative lumbar spine conditions. Not only do the clinical indications
      deserve attention, but also, and most importantly, the patient's anatomic
      characteristics.

PMID- 19574833
TI  - Prediction of surgical view of neurovascular decompression using interactive
      computer graphics.
AB  - OBJECTIVE: To assess the value of an interactive visualization method for
      detecting the offending vessels in neurovascular compression syndrome in patients
      with facial spasm and trigeminal neuralgia. Computer graphics models are created
      by fusion of fast imaging employing steady-state acquisition and magnetic
      resonance angiography. METHODS: High-resolution magnetic resonance angiography
      and fast imaging employing steady-state acquisition were performed preoperatively
      in 17 patients with neurovascular compression syndromes (facial spasm, n = 10;
      trigeminal neuralgia, n = 7) using a 3.0-T magnetic resonance imaging scanner.
      Computer graphics models were created with computer software and observed
      interactively for detection of offending vessels by rotation, enlargement,
      reduction, and retraction on a graphic workstation. Two-dimensional images were
      reviewed by 2 radiologists blinded to the clinical details, and 2 neurosurgeons
      predicted the offending vessel with the interactive visualization method before
      surgery. Predictions from the 2 imaging approaches were compared with surgical
      findings. The vessels identified during surgery were assumed to be the true
      offending vessels. RESULTS: Offending vessels were identified correctly in 16 of
      17 patients (94%) using the interactive visualization method and in 10 of 17
      patients using 2-dimensional images. These data demonstrated a significant
      difference (P = 0.015 by Fisher's exact method). CONCLUSION: The interactive
      visualization method data corresponded well with surgical findings (surgical
      field, offending vessels, and nerves). Virtual reality 3-dimensional computer
      graphics using fusion magnetic resonance angiography and fast imaging employing
      steady-state acquisition may be helpful for preoperative simulation.

PMID- 19574834
TI  - Unusual causes and presentations of hemifacial spasm.
AB  - OBJECTIVE: To evaluate unusual possible causes and clinical presentations of
      hemifacial spasm (HFS). METHODS: The authors reviewed 1642 cases of HFS.
      Assessments were based on clinical features, 3-dimensional time-of-flight
      magnetic resonance angiography, and surgical findings. Causes other than
      neurovascular compression at the root exit zone of the facial nerve were
      investigated and unusual clinical presentations were noted. RESULTS: Nine (0.5%)
      patients had a secondary causative structural lesion, 7 patients had a tumor, and
      the remaining 2 had a vascular malformation. Direct compression by dolichoectatic
      vertebrobasilar artery was noted in 12 (0.7%) patients. In 7 (0.4%) patients,
      only the distal portion of the facial nerve was compressed, and five (0.3%) had
      only venous compression. Bilateral HFS and tic convulsif were encountered in 7
      (0.4%) and 6 (0.37%) patients, respectively. Fifty-six (3.4%) patients were
      younger than 30 years old at the time of microvascular decompression. CONCLUSION:
      HFS can result from tumor, vascular malformation, and dolichoectatic artery.
      Therefore, appropriate preoperative radiological investigations are crucial to
      achieve a correct diagnosis. The authors emphasize that distal compression or
      only venous compression can be responsible for persistent or recurrent symptoms
      postoperatively. In cases of bilateral HFS, a definite differential diagnosis is
      necessary for appropriate therapy. MVD is recommended as the treatment of choice
      in patients younger than 30 years old or patients with painful tic convulsif.

PMID- 19574836
TI  - Virtual histology-intravascular ultrasound in assessment of carotid plaques: ex
      vivo study.
AB  - OBJECTIVE: Virtual histology-intravascular ultrasound (VH-IVUS) has been reported
      to be useful in detecting the components of coronary plaques in vivo. Recently,
      the application of VH-IVUS to peripheral interventions has been evaluated. The
      aim of this study was to examine the extent to which the necrotic core of carotid
      plaques could be assessed accurately by VH-IVUS compared with histopathology.
      METHODS: A total of 37 carotid plaques underwent ex vivo VH-IVUS within 24 hours
      after endarterectomy. Ninety-five segments of virtual histological images were
      matched to histological sections. The area of the necrotic core on histological
      sections was compared with that on virtual histological images. Intraplaque
      hemorrhage (IPH) was histopathologically graded by its severity using
      immunohistochemical staining for glycophorin A as a marker. The relationship of
      the severity of the IPH to the necrotic core was histopathologically evaluated.
      The correlation between the necrotic core or IPH with symptomatology was also
      evaluated. RESULTS: The area of the necrotic core on virtual histological images
      (median, 8.0%; interquartile range, 5.0%-13%) was significantly smaller compared
      with that of the histological sections (median, 50%; interquartile range, 40%
      63%) (P < 0.0001). The Bland-Altman analysis showed poor agreement in the
      necrotic core measurement between virtual histological images and histological
      sections (mean difference, 39.8%; 95% confidence interval, 35.8%-43.8%). Severe
      IPH was significantly associated with a larger necrotic core and symptomatology
      (P < 0.0001 and P = 0.0039, respectively). The area of necrotic core on the
      virtual histological analysis did not correlate with symptomatology (P = 0.70),
      but that on pathological analysis tended to correlate with symptomatology (P =
      0.059). CONCLUSION: In the present virtual histological algorithm, the
      underestimation of the necrotic core was revealed. The lack of a hemorrhage
      component in the virtual histological algorithm is a leading cause of its
      underestimation.

PMID- 19574837
TI  - Expression of CRM1 in human gliomas and its significance in p27 expression and
      clinical prognosis.
AB  - OBJECTIVE: Gliomas are the most common type of primary intracranial tumor.
      Although tumor grade predicts the clinical course of most patients, molecular
      characteristics of individual tumors have emerged as important prognostic factors
      for patients with gliomas. Reduced expression of p27 protein is known as an
      independent prognostic marker in a large variety of cancers and is associated
      with an unfavorable prognosis. It is believed that phosphorylation of p27 on
      Ser10 has been shown to be required for the binding of CRM1, a carrier protein
      for nuclear export. This study assessed whether CRM1, Ser10-phosphorylated p27,
      and p27 correlated with each other, with glioma pathological stage, and with
      patient outcome. METHODS: Immunohistochemical and Western blot analysis were
      performed in 70 cases of human gliomas and normal brain tissues. Survival
      analyses were performed using the Kaplan-Meier method. RESULTS: High CRM1
      expression (80% of cancer cell nuclei stained) was observed in 70 specimens and
      was related to the grade of malignancy. A strong inverse correlation was evident
      between p27 levels and both Ser10-phosphorylated p27 (P < 0.001) and CRM1 level
      (P < 0.001). We also reviewed each grade of tumors separately and investigated
      whether CRM1 expression predicted patient survival within each subgroup. In
      brief, CRM1 overexpression was significantly associated with overall survival (P
      < 0.001). CONCLUSION: The current results showed that CRM1 and p27 expression
      were associated with glioma grade and that high CRM1 protein expression might be
      related to poor outcome.

PMID- 19574835
TI  - Cerebral cavernous malformations: somatic mutations in vascular endothelial
      cells.
AB  - OBJECTIVE: Germline mutations in 3 genes have been found in familial cases of
      cerebral cavernous malformations (CCMs). We previously discovered somatic and
      germline truncating mutations in the KRIT1 gene, supporting the "2-hit" mechanism
      of CCM lesion formation in a single lesion. The purpose of this study was to
      screen for somatic, nonheritable mutations in 3 more lesions from different
      patients and identify the cell type(s) in which somatic mutations occur. METHODS:
      Somatic mutations were sought in DNA from 3 surgically excised, fresh-frozen CCM
      lesions by cloning and screening polymerase chain reaction products generated
      from KRIT1 or PDCD10 coding regions. Laser capture microdissection was used on
      isolated endothelial and nonendothelial cells to determine whether somatic
      mutations were found in endothelial cells. RESULTS: CCM lesions harbor somatic
      and germline KRIT1 mutations on different chromosomes and are therefore
      biallelic. Both mutations are predicted to truncate the protein. The KRIT1
      somatic mutations (novel c.1800delG mutation and previously identified 34
      nucleotide deletion) in CCMs from 2 different patients were found only in the
      vascular endothelial cells lining caverns. No obvious somatic mutations were
      identified in the 2 other lesions; however, the results were inconclusive,
      possibly owing to the technical limitations or the fact that these specimens had
      a small proportion of vascular endothelial cells lining pristine caverns.
      CONCLUSION: The "2-hit" mechanism occurs in vascular endothelial cells lining CCM
      caverns from 2 patients with somatic and Hispanic-American KRIT1 germline
      mutations. Methods for somatic mutation detection should focus on vascular
      endothelial cells lining pristine caverns.

PMID- 19574838
TI  - Pathoanatomic basis for stretch-induced lumbar nerve root injury with a review of
      the literature.
AB  - OBJECTIVE: Persistent pain originating from a dysfunctional lumbar motion segment
      poses significant challenges in the clinical arena. Although the predominance of
      the existing spine literature has addressed nerve root compression as the
      principal cause of pain, it is equally likely that a stretch mechanism may be
      responsible for all or part of the pathology. METHODS: The literature supporting
      the role of stretch damage as a primary cause of nerve root injury and pain was
      systematically reviewed. Pathoanatomic considerations between nerve roots and
      juxtaposed environment are described and correlated with the available
      literature. Potential anatomic relationships that may lead to stretch-induced
      injury are delineated. RESULTS: A dynamic lumbar functional spinal unit that
      encloses a tethered nerve root can create significant stretch and/or compression.
      This phenomenon may be present in a variety of pathological conditions. These
      include anterior, posterior, and rotatory olisthesis as well as degenerative
      conditions such as the loss of disc interspace height and frank multisegment
      spinal deformity. Although numerous studies have demonstrated that stretch can
      result in nerve damage, the pathophysiology that may associate nerve stretch with
      chronic pain has yet to be determined. CONCLUSION: The current literature
      concerning stretch-related injury to nerve roots is reviewed, and a conceptual
      framework for its diagnosis and treatment is proposed and graphically illustrated
      using cadaveric specimens. The dynamic biomechanical and functional
      interrelationships between neural structures and adjacent connective tissue
      elements are particularly important in the face of spinal deformity.

PMID- 19574839
TI  - Molecular alterations associated with aneurysmal remodeling are localized in the
      high hemodynamic stress region of a created carotid bifurcation.
AB  - OBJECTIVE: Although elevated hemodynamics has been speculated to play a key role
      in intracranial aneurysm (IA) initiation, little is known about the specific
      hemodynamic microenvironment that triggers aneurysmal vascular degradation. We
      previously demonstrated maladaptive remodeling characteristic of IA initiation
      occurring in hemodynamic regions of combined high wall shear stress (WSS) and
      high WSS gradient near the apex of an experimentally created carotid bifurcation.
      This study examines whether this remodeling recapitulates the molecular changes
      found in IAs and whether molecular changes also correspond to specific
      hemodynamic environments. METHODS: De novo bifurcations were surgically created
      using both native common carotid arteries in each of 6 dogs. Bifurcations were
      imaged 2 weeks or 2 months after surgery by high-resolution 3-dimensional
      angiography, from which flow fields were obtained by computational fluid dynamics
      simulations. Subsequently, harvested tissues, demonstrating early aneurysmal
      changes near the apex, were immunostained for interleukin-1beta, endothelial and
      inducible nitric oxide synthases, nitrotyrosine, and matrix metalloproteinase-2
      and -9. Spatial distributions of these molecules were comapped with computational
      fluid dynamics results. RESULTS: The aneurysmal wall showed decreased endothelial
      nitric oxide synthase expression compared with surrounding segments, the feeding
      artery, and native controls, whereas all other markers increased. Anti-CD68
      staining indicated the absence of inflammatory cells in the aneurysmal wall.
      Comapping molecular marker distributions with flow fields revealed confinement of
      these molecular changes within the hemodynamic region of high WSS and high,
      positive WSS gradient. CONCLUSION: Aneurysm-initiating remodeling induced by
      combined high WSS and high, positive WSS gradient is associated with molecular
      changes implicated in IAs.

PMID- 19574840
TI  - Simvastatin attenuates microglial cells and astrocyte activation and decreases
      interleukin-1beta level after traumatic brain injury.
AB  - OBJECTIVE: Our previous studies demonstrated that simvastatin promotes
      neurological functional recovery after traumatic brain injury (TBI) in rat;
      however, the underlying mechanisms remain poorly understood. The purpose of this
      study was to investigate the anti-inflammatory effect of simvastatin by measuring
      the level of cytokines and activation of glial cells. METHODS: Controlled
      cortical impact injury was performed in adult male Wistar rats. The rats were
      randomly divided into 3 groups: sham, saline control group, and simvastatin
      treatment group. Simvastatin was administered orally starting at day 1 after TBI
      until animals were killed at days 1, 3, 7, 14, and 35 after treatment. Functional
      outcome was measured using modified neurological severity scores. Enzyme-linked
      immunosorbent assay and immunohistochemical staining were used to measure the
      expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha and
      to identify activated microglial cells and astrocytes. RESULTS: At days 1 and 3
      after simvastatin or saline treatment, cytokine levels in the lesion boundary
      zone were significantly higher in the simvastatin- and saline-treated rats
      compared with the sham group, peaking at day 3. Simvastatin only reduced the
      level of IL-1beta but not IL-6 and tumor necrosis factor-alpha, compared with the
      saline group. Also, simvastatin significantly reduced the number of activated
      microglial cells and astrocytes compared with the saline control animals. There
      was also a trend toward improvement of modified neurological severity score,
      reaching statistical significance (P = 0.003) toward the end of the trial.
      CONCLUSION: Our data demonstrate that TBI causes inflammatory reaction, including
      increased levels of IL-1beta, IL-6, and tumor necrosis factor-alpha, as well as
      activated microglial cells. Simvastatin selectively reduces IL-1beta expression
      and inhibits the activation of microglial cells and astrocytes after TBI, which
      might be one of the mechanisms underlying the therapeutic benefits of simvastatin
      treatment of TBI.

PMID- 19574841
TI  - Long-term benefits after treatment of traumatic brain injury with simvastatin in
      rats.
AB  - OBJECTIVE: This study was designed to investigate the long-term effects of
      simvastatin treatment after traumatic brain injury (TBI) in rats. METHODS: Adult
      female Wistar rats (n = 24) were injured with controlled cortical impact and
      divided into 3 groups. The first 2 groups were treated with simvastatin (0.5 or
      1.0 mg/kg) administered orally for 14 days starting 1 day after TBI. The third
      group (control) received phosphate-buffered saline orally for 14 days.
      Neurological functional outcome was measured with modified neurological severity
      scores performed 1 day before TBI; on days 1, 4, 7, 14 after TBI; and biweekly
      thereafter. All animals were sacrificed 3 months after TBI. Brain tissues of half
      of the animals were processed for preparation of paraffin-embedded sections for
      immunohistological studies. The remaining half were frozen for enzyme-linked
      immunosorbent assay studies for quantification of brain-derived neurotrophic
      factor (BDNF) in the hippocampus and cortex. RESULTS: The results showed that
      both doses of simvastatin significantly improved functional outcome compared with
      the control, with no difference between the 2 doses. Simvastatin treatment of 1.0
      mg/kg increased the number of morphologically intact neurons in the hippocampus,
      but treatment of 0.5 mg/kg had no significant effect. Enzyme-linked immunosorbent
      assay studies showed that 0.5 mg/kg simvastatin significantly increased BDNF
      levels within the hippocampus, but 1.0 mg/kg had no significant effect. Neither
      dose had any effect on BDNF levels within the cortex. CONCLUSION: Simvastatin
      treatment provides long-lasting functional improvement after TBI in rats. It also
      enhances neuronal survival in the hippocampus and increases BDNF levels in the
      hippocampus secondary to simvastatin treatment.

PMID- 19574842
TI  - Adjuvant treatment with locally delivered OncoGel delays the onset of paresis
      after surgical resection of experimental spinal column metastasis.
AB  - OBJECTIVE: The optimal management of spinal column metastatic disease is
      controversial. Local chemotherapy delivery systems allow targeted high-dose
      adjuvant therapy. We evaluated whether injection of OncoGel paclitaxel-releasing
      biodegradable polymer (Protherics, Inc., West Valley City, UT) into the tumor
      resection cavity at the time of surgery would improve the efficacy of surgical
      resection with or without external beam radiotherapy (XRT) in a rat model of
      spinal column metastases. METHODS: Fischer-344 rats (Charles River Laboratories,
      Wilmington, MA) underwent a transabdominal approach for implantation of a CRL
      1666 breast adenocarcinoma cell line within the L6 vertebral body. In experiment
      1, 7 days after tumor implantation, animals underwent 1 of 2 treatments or no
      treatment (n = 8 per group): control (no treatment); surgery alone (L6
      corpectomy); or surgery + OncoGel (L6 corpectomy with OncoGel implantation into
      the resection cavity). In experiment 2, 7 days after tumor implantation, animals
      underwent 1 of 2 treatments or no treatment (n = 8 per group): control (no
      treatment); surgery + XRT (L6 corpectomy followed by XRT [total 20 Gy]); or
      surgery + XRT + OncoGel (L6 corpectomy with OncoGel implantation followed by
      XRT). In experiment 3, 7 days after tumor implantation, animals underwent 1 of 2
      treatments or no treatment (n = 8 per group): control (no treatment); XRT alone
      (total 20 Gy); or XRT + OncoGel. Daily hindlimb function was assessed using the
      Basso, Beattie, and Bresnahan (BBB) scale (range, 1-21). RESULTS: In experiment
      1, both treatment groups had delayed onset of paresis compared with control.
      Compared with surgery alone, surgery + OncoGel resulted in superior median BBB
      scores on posttreatment days 9 (21 versus 19, P < 0.001) through 14 (11 versus 8,
      P < 0.005). In experiment 2, both treatment groups had delayed onset of paresis
      compared with control. Compared with surgery + XRT, surgery + XRT + OncoGel
      resulted in superior median BBB scores on posttreatment days 13 (21 versus 19, P
      < 0.001) through 17 (12 versus 8, P < 0.005). Median time to loss of ambulation
      (BBB scale score </=7) was maximized by the addition of OncoGel to surgery plus
      XRT: control (8.5 days), surgery alone (13.5 days), surgery + OncoGel (16 days),
      surgery + XRT (17 days), and surgery + XRT + OncoGel (19 days). In experiment 3,
      both treatment groups had delayed onset of paresis compared with control.
      Compared with XRT alone, XRT + OncoGel resulted in superior median BBB scores on
      posttreatment days 6 (21 versus 19, P < 0.001) through 11 (13 versus 8, P <
      0.005). However, compared with surgery + XRT + OncoGel, XRT + OncoGel resulted in
      worse median BBB scores on posttreatment days 8 (20 versus 21, P < 0.01) through
      13 (7 versus 19, P < 0.005). CONCLUSION: In a rat model of spinal metastatic
      disease, local delivery of OncoGel increased the efficacy of surgery and
      radiotherapy and delayed the onset of neurological decline. These results suggest
      that OncoGel may be an effective adjuvant therapy in the operative management of
      metastatic spinal column tumors and that combining local chemotherapy with
      surgery and adjuvant radiotherapy may improve outcomes of this disease.

PMID- 19574843
TI  - Dandy'S disc.
AB  - Much has been written about the accomplishments of Walter E. Dandy, and he
      remains one of the seminal figures in neurosurgery. He is perhaps best known for
      his scientific contributions to our understanding of cerebrospinal fluid and
      pituitary gland physiology and his clinical contributions of ventriculography,
      cerebellopontine angle approaches for a variety of posterior fossa pathology, and
      the first clipping of a cerebral aneurysm. What is not as well known is that
      Dandy was the first to accurately describe and treat lumbar disc herniation. He
      published a thorough clinical, operative, and pathological description in a 1929
      Archives of Surgery article, titled "Loose Cartilage from Intervertebral Disk
      Simulating Tumor of the Spinal Cord." His publication predates by 5 years the
      well-known 1934 Mixter and Barr article "Rupture of the Intervertebral Disc with
      Involvement of the Spinal Canal."

PMID- 19574844
TI  - Starting small and early for research funding.
AB  - Many new nursing leaders assuming deanships or assistant or interim deanships
      have limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 19574845
TI  - Sources of fully developed course materials on the Web.
AB  - In this bimonthly series, the author examines how nurse educators can use
      Internet and Web-based computer technologies such as search, communication, and
      collaborative writing tools; social networking and social bookmarking sites;
      virtual worlds; and Web-based teaching and learning programs. This article
      describes sources of ready-to-use teaching-learning materials available free on
      the Internet. Techniques to find and evaluate these resources are discussed.

PMID- 19574846
TI  - Integrating gerontology content in the clinical setting.

PMID- 19574848
TI  - An innovative faculty toolkit: simulation success.

PMID- 19574849
TI  - Using an online community board for end-of-life care teaching, learning, and
      student engagement.

PMID- 19574850
TI  - Implementing the virtual reality learning environment: Second Life.
AB  - Today, faculty members are challenged to find meaningful learning activities that
      enhance online nursing education. Second Life is an innovative Internet-based
      strategy that may be used to engage students in active learning. The authors
      discuss how this technology was implemented into an accelerated online nursing
      program.

PMID- 19574851
TI  - Effectiveness, challenges, and perceptions of classroom participation systems.
AB  - A technology-driven generation of students expects faculty to use innovative and
      interactive approaches to teaching. To address this issue, the authors discuss
      their use of one classroom participation system, the i>Clicker, and student
      outcomes.

PMID- 19574855
TI  - How to read and really use an item analysis.
AB  - A frequent challenge for nursing faculty is to write a test that effectively
      evaluates learning and prepares students to be successful on the NCLEX-RN
      examination. Use of item analysis is an approach often used to provide an
      objective evaluation of examinations. Interpreting these analyses, however, can
      be frustrating. The authors provide an explanation of the various components of
      an item analysis, how to make an analysis useful for faculty, and how to use the
      components of an item analysis in revising tests.

PMID- 19574853
TI  - Palliative care for children: preparing undergraduate nursing students.
AB  - Children with life-threatening illnesses rarely benefit from palliative services.
      Because nurses spend more time with dying children than any other healthcare
      professional does, it is essential that they are prepared to address the
      complicated physical, psychological, legal, ethical, and spiritual issues
      associated with terminal illness and death. The authors discuss a course that
      provides students with the knowledge, skills, and attitude needed to provide
      comprehensive care for pediatric patients and their families.

PMID- 19574857
TI  - Essential tools for a study abroad nursing course.
AB  - Research results indicate that study-abroad programs have positive learning
      outcomes. Drawing on their experiences as faculty in a study-abroad program for
      student nurses, the authors identify basic educational components and learning
      activities that can be used to maximize students' learning in a study-abroad
      program in a low-resource country.

PMID- 19574858
TI  - The SBAR communication technique: teaching nursing students professional
      communication skills.
AB  - The Joint Commission and Institute for Healthcare Improvement have mandated
      healthcare organizations to improve professional communication. Nursing students
      lack experience in communicating with physicians. As a result, recent graduates
      may not be prepared to meet the demands of professional communication to ensure
      patient safety. The authors discuss the SBAR (situation, background, assessment,
      recommendations) communication technique implemented during a 2-day simulation
      exercise that provided an organized logical sequence and improved communication
      and prepared graduates for transition to clinical practice.

PMID- 19574860
TI  - A step-by-step approach to curriculum review.
AB  - Given the need for periodic curriculum review to maintain program quality and
      continually improve student learning experiences, a plan was designed to manage
      the complexities of curriculum review in an efficient and organized manner. The
      authors describe how using a master curriculum review plan actively involved all
      full-time undergraduate faculty in the evaluation process and facilitated
      completion of the review in a reasonable time frame.

PMID- 19574862
TI  - The economic implications of a multimodal analgesic regimen for patients
      undergoing major orthopedic surgery: a comparative study of direct costs.
AB  - BACKGROUND AND OBJECTIVES: Total knee and total hip arthoplasty (THA) are 2 of
      the most common surgical procedures performed in the United States and represent
      the greatest single Medicare procedural expenditure. This study was designed to
      evaluate the economic impact of implementing a multimodal analgesic regimen
      (Total Joint Regional Anesthesia [TJRA] Clinical Pathway) on the estimated direct
      medical costs of patients undergoing lower extremity joint replacement surgery.
      METHODS: An economic cost comparison was performed on Mayo Clinic patients (n =
      100) undergoing traditional total knee or total hip arthroplasty using the TJRA
      Clinical Pathway. Study patients were matched 1:1 with historical controls
      undergoing similar procedures using traditional anesthetic (non-TJRA) techniques.
      Matching criteria included age, sex, surgeon, type of procedure, and American
      Society of Anesthesiologists (ASA) physical status (PS) classification. Hospital
      based direct costs were collected for each patient and analyzed in standardized
      inflation-adjusted constant dollars using cost-to-charge ratios, wage indexes,
      and physician services valued using Medicare reimbursement rates. The estimated
      mean direct hospital costs were compared between groups, and a subgroup analysis
      was performed based on ASA PS classification. RESULTS: The estimated mean direct
      hospital costs were significantly reduced among TJRA patients when compared with
      controls (cost difference, 1999 dollars; 95% confidence interval, 584-3231
      dollars; P = 0.0004). A significant reduction in hospital-based (Medicare Part A)
      costs accounted for the majority of the total cost savings. CONCLUSIONS: Use of a
      comprehensive, multimodal analgesic regimen (TJRA Clinical Pathway) in patients
      undergoing lower extremity joint replacement surgery provides a significant
      reduction in the estimated total direct medical costs. The reduction in mean cost
      is primarily associated with lower hospital-based (Medicare Part A) costs, with
      the greatest overall cost difference appearing among patients with significant
      comorbidities (ASA PS III-IV patients).

PMID- 19574861
TI  - Comparison of 3 intensities of stimulation threshold for brachial plexus blocks
      at the midhumeral level: a prospective, double-blind, randomized study.
AB  - BACKGROUND: We conducted this prospective randomized study to compare the success
      rate and the onset time between 3 intensities of stimulation threshold (<0.5, 0.5
      0.64, and 0.65-0.8 mA) when using a peripheral nerve stimulation at the
      midhumeral level. METHODS: Sixty-nine adult patients undergoing elective hand
      surgery were studied. Blocks were performed using conventional nerve stimulation
      technique. Needle advance began at 2 mA (1 Hz, 0.1 millisecond). When motor
      response (MR) occurred at less than 0.5 mA, needle position was fixed for "group
      <0.5 mA." For "group 0.5-0.64 mA," the needle was withdrawn until MR occurred at
      greater than 0.5 mA and disappeared at less than 0.5 mA. For "group >0.65 mA,"
      the needle was withdrawn until MR occurred at greater than 0.65 mA and
      disappeared at less than 0.65 mA. For each group, patients received 8 mL of
      ropivacaine 7.5 mg/mL on the 4 nerves (radial, median, ulnar, and
      musculocutaneous). Primary end point was the number of failed radial nerve
      sensory blocks at 30 mins. RESULTS: The time to perform the block was not
      different between the 3 groups (17 mins [SD, 7 mins] vs 13 mins [SD, 8 mins] and
      13 mins [SD, 4 mins], respectively). The time required to obtain a complete
      sensory block was shorter for the 4 nerves in group <0.5 mA, with a statistical
      significance for radial and musculocutaneous nerves in group <0.5 mA versus group
      0.5-0.64 mA and group >0.65 mA. Patients in group <0.5 mA had a greater success
      rate for complete sensory radial nerve compared with those of group 0.5-0.64 mA
      and group >0.65 mA at any interval times between 5 and 30 mins (P = 0.0001).
      Supplemental local anesthesia was provided for the 3 groups more frequently for
      the median nerve, with no difference between groups. Group >0.65 mA required 5
      general anesthesias (20%) as compared with 1 (4%) in group <0.5 mA (P < 0.05). No
      adverse event (dysesthesia) occurred after 48 hrs and 45 days. CONCLUSION: We
      conclude that intensity of stimulation influenced onset time and success rate.

PMID- 19574863
TI  - Prevalence and risk factors predisposing to coagulopathy in patients receiving
      epidural analgesia for hepatic surgery.
AB  - BACKGROUND AND OBJECTIVES: Patients undergoing liver resection may have marginal
      preoperative liver function, extensive intraoperative blood loss, and
      perioperative hepatic dysfunction. We evaluated the prevalence and types of
      coagulopathic conditions that occur in patients with epidural catheters
      undergoing hepatic resection. METHODS: A retrospective chart review was conducted
      of all patients undergoing hepatic surgery who received epidural analgesia
      between June 1995 and September 2003 at our institution. Forty-nine surgical
      cases had an epidural catheter placed preoperatively. Data were collected
      included age, weight, American Society of Anesthesiologists physical status;
      preoperative partial thromboplastin time (PTT), international normalized ratio
      (INR), and platelet count (PLT); estimated blood loss (EBL); and volume of
      hepatic resection. RESULTS: Forty-nine cases received an epidural catheter before
      hepatic resection. Preoperative PTT, INR, and PLTs were within reference ranges
      in 47 of 49 patients. Twenty-three (47%) of 49 patients were coagulopathic in the
      postoperative period. The most common abnormality was an INR greater than 1.4 in
      16 patients. Nine patients had a PLT of less than 100,000/microL, and 4 patients
      had a PTT of greater than 40 secs. Patients who developed a hemostatic
      abnormality were likely to have greater median EBL (400 vs 1400 mL; Mann-Whitney
      = 100.5, P = 0.0004) and have a greater median volume of liver resected (166 vs
      1688 cm; Mann-Whitney = 57.0, P = 0.0004). There was no causal relationship to
      preoperative laboratory values, age, weight, or American Society of
      Anesthesiologists classification. DISCUSSION: A high prevalence of hemostatic
      abnormalities in patients undergoing major hepatic resection while receiving
      epidural analgesia occurred. Important considerations may include discussion with
      the surgical team, measuring coagulation, and heightened clinical monitoring in
      the postoperative period.

PMID- 19574864
TI  - Paravertebral block in inguinal hernia surgeries: two segments or 4 segments?
AB  - BACKGROUND AND OBJECTIVES: In this study, we compare paravertebral block (PVB) of
      the T10 and L1 segments and multiple-segment PVB for anesthesia and analgesia in
      inguinal hernia surgeries. METHODS: Anatomic study was performed on 3 cadavers. A
      15-mL methylene blue solution was injected at the T10 level and then an
      additional 5-mL dye injection at L1 level. Fifty patients were included in the
      study. Patients in group 1 (n = 25) underwent PVB of 2 segments at the T10 and L1
      vertebrae levels on the same side as the hernia, whereas patients in group 2 (n =
      25) underwent PVB through 4 segments at T10, T11, T12, and L1 on the same side as
      the hernia. Perioperative propofol/remifentanil consumption, surgery start time,
      time to perform the block, duration of sensory block, postoperative visual analog
      scale scores, and complications were evaluated. RESULTS: Any passage down to the
      T12 level was not observed after injection at the T10 level and also only after
      additional 5-mL dye injection at the L1 level; the genitofemoral, ilioinguinal,
      iliohypogastric, and lateral femoral cutaneous nerves were stained with dye in
      cadavers. The times for block application were 5 mins (SD, 1 min) in group 1 and
      16 mins (SD, 4 mins) in group 2 (P < 0.001). The surgery start time was 25 mins
      (SD, 3 mins) in group 1 and 27 mins (SD, 6 mins) in group 2 (P = 0.234). In both
      groups, propofol and remifentanil were used in similar quantities during the
      perioperative period. Use of paracetamol tablets was similar in both groups (P >
      0.05). Whereas none of the patients in group 1 displayed motor block or
      contralateral spread, 2 patients in group 2 displayed contralateral spread, and
      motor block was observed in 1 patient. Twenty-three patients (92%) in group 1 and
      24 patients (96%) in group 2 were satisfied with the method (P > 0.05).
      CONCLUSION: Two-segment PVB can be an alternative to 4-segment PVB in inguinal
      hernia surgeries. Decreasing the number of injections required in this technique
      may further increase patient comfort and decrease complications.

PMID- 19574865
TI  - Extended-release epidural morphine (DepoDur) following epidural bupivacaine in
      patients undergoing lower abdominal surgery: a randomized controlled
      pharmacokinetic study.
AB  - BACKGROUND AND OBJECTIVES: The primary objective was to compare the serum
      pharmacokinetic profile of a single dose of extended-release epidural morphine
      (EREM) administered alone versus 15 to 60 mins after an analgesic epidural dose
      of bupivacaine. METHODS: This multicenter study enrolled 144 patients, 18 years
      or older, with scheduled lower abdominal surgery under general anesthesia.
      Patients were randomly assigned to a single 15-mg dose of EREM; the same dose
      administered 15, 30, or 60 mins after epidural bupivacaine (20 mL 0.25%); or
      epidural placebo (normal saline) administered 15, 30, or 60 mins after
      bupivacaine. Postoperatively, fentanyl patient-controlled analgesia was offered
      for breakthrough pain. Multiple serum samples were analyzed for morphine and
      morphine metabolites. Safety and efficacy were assessed. RESULTS: The mean
      maximum serum concentration and area under the concentration-time curve for
      morphine and metabolites were not significantly different when EREM was
      administered alone versus 15, 30, or 60 mins after bupivacaine. Median time to
      maximum serum concentration and median apparent terminal elimination half-life
      were also comparable. Total fentanyl patient-controlled analgesia consumption was
      comparable among all EREM groups (with/without prior bupivacaine) but
      significantly (P < 0.05) lower compared with the bupivacaine + placebo group.
      Nausea, vomiting, and dizziness were consistently more frequent in groups
      receiving EREM after bupivacaine versus EREM alone. CONCLUSIONS: The
      pharmacokinetic and efficacy profiles of a single 15-mg dose of EREM were not
      significantly altered when administered 15, 30, or 60 mins after an analgesic
      epidural dose of bupivacaine.

PMID- 19574866
TI  - Calcium chloride prolongs the effects of lidocaine and bupivacaine in rat sciatic
      nerve.
AB  - BACKGROUND AND OBJECTIVES: Elevated extracellular calcium ion has been shown to
      shift the voltage dependence of Na+- and K+-ion channels rightward, making the
      nerve less excitable. We hypothesized that calcium chloride (CaCl2) when used as
      an adjuvant prolongs and intensifies the block by local anesthetics (LAs). We
      investigated the effects of LAs combined with calcium in rat sciatic nerve
      blockade and in cultured rat GH3 cells expressing Na+ channels. Furthermore, we
      tested for histologic changes due to CaCl2. METHODS: We anesthetized rats with
      sevoflurane, exposed the sciatic nerves, and injected 0.2 mL of 1% lidocaine or
      0.1% bupivacaine, alone or coadministered with 0.625%, 1.25%, 2.5%, or 5% CaCl2
      (n = 8-10 per group). We assessed the complete-block time and complete-recovery
      time of proprioception, motor function, and nocifensive reaction. To elucidate
      the mechanism of nerve block, we performed electrophysiology experiments in
      cultured rat GH3 cells. Sciatic nerves were harvested at day 7 and stained with
      hemotoxylin/eosin. RESULTS: The addition of CaCl2 overall prolonged the duration
      of blockade by lidocaine or bupivacaine. Adding 10 mM CaCl2 to 300 microM
      lidocaine caused a right shift of the steady-state Na+-channel inactivation
      curve, indicating that the CaCl2 reduced the potency of lidocaine. Rat sciatic
      nerves treated with 1% lidocaine coadministered with 5% CaCl2 showed microscopic
      signs of neurotoxicity. CONCLUSIONS: The mechanism of prolonged nerve block of
      CaCl2 coadministered with LAs seems to be a raised threshold for nerve
      excitation. Major histopathologic changes at higher concentrations of CaCl2 are
      evident, and therefore, clinical application as an adjuvant to LAs seems
      unlikely.

PMID- 19574867
TI  - Ultrasound-guided cervical selective nerve root block: a fluoroscopy-controlled
      feasibility study.
AB  - BACKGROUND AND OBJECTIVES: Reports of intravascular injection during cervical
      transforaminal injections, even after confirmation by contrast fluoroscopy, have
      led some to question the procedure's safety. As ultrasound allows for
      visualization of soft tissues, nerves, and vessels, thus potentially improving
      precision and safety, we evaluated its feasibility in cervical nerve root
      injections. METHODS: This is a prospective series of 10 patients who received
      cervical nerve root injections using ultrasound as the primary imaging tool, with
      fluoroscopic confirmation. Our radiologic target point was the posterior aspect
      of the intervertebral foramen just anterior to the superior articular process in
      the oblique view and at the midsagittal plane of the articular pillars in the
      anteroposterior (AP) view. RESULTS: The needle was exactly at the target point in
      5 patients in the oblique view and in 3 patients in the AP views. The needle was
      within 3 mm in all patients in the lateral oblique view and in 8 patients in the
      AP view. In the remaining 2 patients, the needle was within 5 mm from the
      radiologic target. In 4 patients, we were able to identify vessels at the
      anterior aspect of the foramen, whereas 2 patients had critical vessels at the
      posterior aspect of the foramen, and in 1 patient, this artery continued medially
      into the foramen, most likely forming or joining a segmental feeder artery. In
      both cases, the vessels might well have been in the pathway of a needle correctly
      positioned under fluoroscopic control. CONCLUSIONS: Our case series shows the
      feasibility of using ultrasound imaging to guide selective cervical nerve root
      injections. It may facilitate identifying critical vessels at unexpected
      locations relative to the intervertebral foramen and avoiding injury to such
      vessels, which is the leading cause of the reported complications from cervical
      nerve root injections. A randomized controlled trial to compare the effectiveness
      and safety of ultrasound imaging against other imaging techniques seems
      warranted.

PMID- 19574868
TI  - Ultrasound machine comparison: an evaluation of ergonomic design, data
      management, ease of use, and image quality.
AB  - BACKGROUND AND OBJECTIVES: The use of ultrasound technology for vascular access
      and regional anesthesia is gaining widespread acceptance among anesthesia
      providers. As a result, many group practices and medical institutions are
      considering purchasing ultrasound equipment. Currently, comparative information
      regarding the ergonomic design, physical and adjustable features, data
      management, ease of use, cost, and image quality of various ultrasound machines
      is not available. The primary goal of this investigation was to develop an
      objective process of evaluating ultrasound equipment before purchase. The process
      of evaluation used in the current investigation may be used when comparing a
      variety of medical technologies. METHODS: A randomized, side-by-side comparative
      evaluation of 7 different ultrasound machine models was performed. Sixteen
      resident physicians without prior ultrasound experience (inexperienced providers)
      completed a formal evaluation of each machine model after performing a
      standardized machine configuration and performance checklist. Inexperienced
      providers and 10 faculty members experienced in ultrasound-guided regional
      anesthesia evaluated the image quality of 2 standardized images acquired from
      each machine model. RESULTS: Overall, evaluators rated questions on the machine
      evaluation form as "very good" or "outstanding" 70% or more of the time for all
      machine models. The largest, most complex ultrasound machine was rated as having
      the best image quality by both inexperienced and experienced providers.
      Ultrasound machine models with the simplest ergonomic design and user interface
      were rated highest by inexperienced study participants. CONCLUSIONS: Anesthesia
      providers considering an ultrasound equipment purchase should objectively
      evaluate machine models that have features most important to their own clinical
      practice. Ergonomic design, physical and adjustable features, data management,
      ease of use, image quality, and cost are important features to consider when
      evaluating an ultrasound machine.

PMID- 19574869
TI  - Is ultrasound guidance superior to conventional nerve stimulation for coracoid
      infraclavicular brachial plexus block?
AB  - BACKGROUND AND OBJECTIVES: In different peripheral nerve blocks, it has been
      speculated that needle guidance by ultrasound improves onset time and success
      rate compared with the more frequently used nerve stimulation-guided technique.
      In the present study, we tested the hypothesis that ultrasound guidance improves
      onset time of coracoid infraclavicular brachial plexus block (IBPB) when compared
      with a nerve stimulation-guided technique. METHODS: Seventy patients scheduled
      for hand or forearm surgery were randomly assigned to receive coracoid IBPB using
      either ultrasound guidance (group U, n = 35), or nerve stimulation (group S, n =
      35). Patients were assessed for sensory and motor block every 5 mins after
      injection of local anesthetic. Onset time, the primary end point, was defined as
      the time required for complete sensory and motor block. Time required to perform
      the block, success rate, and time to resolution of motor blockade were also
      recorded (secondary end points). RESULTS: Onset of complete sensory and motor
      blockade was similar in the 2 groups (17 mins [8 mins] in group U and 19 mins [8
      mins] in group S; P = 0.321). Time required to perform the block was shorter in
      group U (3 mins [1 min]) as compared with group S (6 mins [2 mins]; P < 0.0001).
      No differences were observed in success rate (89% in group U and 91% in group S;
      P = 0.881) and time to resolution of motor blockade (237 mins [45 mins] in group
      U and 247 mins [57 mins] in group S; P = 0.418). CONCLUSIONS: The present
      investigation demonstrates that ultrasound guidance and nerve stimulation provide
      similar onset time, success rate, and duration of motor blockade for coracoid
      IBPB; however, ultrasound guidance reduces the time required to perform the
      block.

PMID- 19574870
TI  - Comparison of the transarterial axillary block and the ultrasound-guided
      infraclavicular block for upper extremity surgery: a prospective randomized
      trial.
AB  - BACKGROUND AND OBJECTIVES: The transarterial axillary block and the ultrasound
      guided infraclavicular block are both effective methods of anesthetizing the
      upper extremity. This study compares these methods with respect to subjective
      postoperative dysesthesias, block adequacy, patient comfort, and patient
      satisfaction. METHODS: Two hundred thirty-two patients were randomized to receive
      an ultrasound-guided infraclavicular block or a transarterial axillary block for
      upper extremity surgery. Block placement, motor and sensory testing, and block
      adequacy data were recorded. The subjects were contacted by a blinded research
      assistant at 2 and 10 days postoperatively to assess for the presence of
      dysesthesias and pain and to assess patient satisfaction. RESULTS: The 2
      techniques were similar with respect to block performance time and adequacy of
      the block for surgery. There was no significant difference between the blocks in
      terms of postoperative dysesthesias (23.9% in the axillary group vs 17.1% in the
      infraclavicular group at 2 days, P = 0.216, and 11.0% vs 6.31% at 10 days, P =
      0.214). None of the dysesthesias were permanent. The infraclavicular block had a
      lower incidence of paresthesias during placement (P = 0.035) and was associated
      with less pain at the block site (P = 0.010 at 2 days, P = 0.002 at 10 days).
      More patients were willing to undergo the infraclavicular block as a future
      anesthetic when compared with the axillary block (P = 0.025 at 10 days).
      CONCLUSIONS: There is no significant difference between the 2 techniques in terms
      of adequacy for surgery and subjective postoperative dysesthesias. The ultrasound
      guided infraclavicular block is associated with greater patient comfort and
      willingness to undergo the same anesthetic when compared with the transarterial
      axillary block.

PMID- 19574871
TI  - A prospective, randomized comparison between ultrasound-guided supraclavicular,
      infraclavicular, and axillary brachial plexus blocks.
AB  - BACKGROUND: This prospective, randomized, observer-blinded study compared
      ultrasound-guided supraclavicular (SCB), infraclavicular (ICB), and axillary
      (AXB) brachial plexus blocks for upper extremity surgery of the elbow, forearm,
      wrist, and hand. METHODS: One hundred twenty patients were randomly allocated to
      receive an ultrasound-guided SCB (n = 40), ICB (n = 40), or AXB (n = 40).
      Performance time (defined as the sum of imaging and needling times) and the
      number of needle passes were recorded during the performance of the block.
      Subsequently, a blinded observer recorded the onset time, block-related pain
      scores, success rate (surgical anesthesia), and the incidence of complications.
      The main outcome variable was the total anesthesia-related time, defined as the
      sum of performance and onset times. RESULTS: No differences were observed between
      the 3 groups in terms of total anesthesia-related time (23.1-25.5 mins), success
      rate (95%-97.5%), block-related pain scores, vascular puncture, and paresthesia.
      Compared with the supraclavicular and infraclavicular approaches, ultrasound
      guided AXBs required a higher number of needle passes (6.1 [SD, 2.0] vs 2.0-2.6
      [SD, 1.1-1.8]; both P < or = 0.001), a longer needling time (7.4 mins [SD, 2.2
      mins] vs 4.9-5.5 mins [SD, 1.9-4.2 mins]; both P < or = 0.016), and a longer
      performance time (8.5 mins [SD, 2.3 mins] vs 6.0-6.2 mins [SD, 2.1-4.5 mins];
      both P < or = 0.008). Supraclavicular blocks resulted in a higher rate of Horner
      syndrome (37.5% vs 0%-5%; both P < 0.001). CONCLUSION: Adjunctive ultrasonography
      results in similar success rates, total anesthesia-related times, and block
      related pain scores for the SCB, ICB, and AXB.

PMID- 19574872
TI  - Two cases of Horner syndrome after administration of an epidural test dose that
      did not recur with subsequent epidural activation.
AB  - OBJECTIVE: We describe 2 cases of Horner syndrome after epidural test dose
      injections in thoracic surgery patients. The Horner syndrome was transient and
      did not recur with full epidural activation and infusion. CASE REPORT: Two
      patients undergoing thoracic surgery procedures received preoperative midthoracic
      epidural catheters for postoperative analgesia. Following the 3-mL 1.5% lidocaine
      test dose, a unilateral Horner syndrome was observed. No other signs and symptoms
      of high epidural blockade were seen, and the Horner syndrome subsequently
      resolved. After epidurogram confirmation of proper catheter position and at the
      conclusion of surgery, the epidural was activated with an appropriate bolus and
      infusion dose without recurrence of the Horner syndrome. CONCLUSIONS: Two cases
      of Horner syndrome presenting after administration of an epidural test dose are
      reported. This uncommon initial finding could not be reproduced with subsequent
      epidural activation, perhaps suggesting that initial conditions within the
      epidural space had been altered. Successful utilization of neuraxial regional
      analgesia was achieved with careful postoperative monitoring of the patients.

PMID- 19574873
TI  - An animal model for teaching ultrasound-guided peripheral nerve blocks.

PMID- 19574874
TI  - Subcutaneous catheter tunneling.

PMID- 19574875
TI  - Methods to ease placement of stimulating catheters during in-plane ultrasound
      guided femoral nerve block.

PMID- 19574876
TI  - The ultrasound-guided block needle holster.

PMID- 19574877
TI  - Useful side handle for holding needle during ultrasound-guided regional
      anesthesia.

PMID- 19574878
TI  - Supraclavicular brachial plexus block-variant relation of brachial plexus to
      subclavian artery on the first rib.

PMID- 19574879
TI  - Anomalous anatomy of the brachial plexus identified during ultrasound-guided
      interscalene plexus block.

PMID- 19574880
TI  - Closure on retraction of articles by Dr. Reuben.

PMID- 19574881
TI  - The risk of very long-term brain dysfunction in treated adolescents with
      perinatally acquired HIV-1 infection.

PMID- 19574882
TI  - Impaired neurocognition in HIV-infected patients: antecedents and treatment.

PMID- 19574883
TI  - Diagnostic utility of SALL4 in extragonadal yolk sac tumors: an
      immunohistochemical study of 59 cases with comparison to placental-like alkaline
      phosphatase, alpha-fetoprotein, and glypican-3.
AB  - Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are
      malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be
      challenging without immunohistochemical markers but markers used for diagnosing
      these tumors such as placental-like alkaline phosphatase (PLAP), alpha
      fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity.
      In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a
      novel diagnostic marker for YSTs and other types of primitive germ cell tumors.
      Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27
      primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by
      immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican
      3. In addition, we performed immunostains for pancytokeratin, epithelial membrane
      antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed
      strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in
      58) and 10 (17%) of them also showed focal epithelial membrane antigen staining
      (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was
      seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor
      cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the
      staining was often focal (in less than 30% tumor cells) (28 of 39 cases).
      Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%);
      however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all
      59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less
      than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and
      60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained
      with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with
      glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells
      stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate
      that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for
      extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3
      for extragonadal YSTs.

PMID- 19574884
TI  - Evaluation of venous invasion by Elastica van Gieson stain and tumor budding
      predicts local and distant metastases in patients with T1 stage colorectal
      cancer.
AB  - Evaluation of pathologic predictors of metastases in T1 stage colorectal cancer
      may be difficult with hematoxylin and eosin (HE) staining alone. The aim of this
      study was to clarify the role of pathologic predictors by using
      immunohistochemical staining and Elastica van Gieson (EVG) staining. One hundred
      and twenty-four patients who underwent bowel resection for single T1 stage
      colorectal cancer from 1990 to 2004 in 1 institution were studied. D2-40, EVG
      staining, and CAM5.2 were used to detect lymphatic invasion, venous invasion, and
      tumor budding, respectively. These 3 factors were separately evaluated based on
      HE staining. Histology was reviewed by 1 pathologist. Lymph node metastases in
      the surgical specimen were the standard reference, and distant metastases were
      identified by periodic computed tomography for 2 years or more after surgery. A
      logistic regression model was applied to analyze risk factors for lymph node
      metastases and a Cox regression model for distant metastases. In predicting lymph
      node metastases, univariate analysis demonstrated significance for all predictors
      except venous invasion by HE staining. Multivariate analysis showed that venous
      invasion by EVG and tumor budding by HE showed significance as predictors. In
      predicting distant metastases, univariate analysis showed significance for
      lymphatic invasion shown by D2-40, tumor budding shown by CAM5.2 and HE, and
      lymph node metastases. Multivariate analysis showed only venous invasion by EVG
      stain as being significantly associated with distant metastases (P=0.001). In
      conclusion, venous invasion evaluated shown by EVG staining is a useful
      pathologic predictor for metastases in T1 stage colorectal cancer.

PMID- 19574885
TI  - Overlapping features between dedifferentiated liposarcoma and undifferentiated
      high-grade pleomorphic sarcoma.
AB  - Dedifferentiated liposarcoma (DDL), occurring in up to 10% of well differentiated
      liposarcoma cases, has similar histologic features to that of undifferentiated
      high-grade pleomorphic sarcoma (UHGPS); the former develops in a background of
      atypical lipomatous tumors/well differentiated liposarcoma, whereas the latter
      shows no specific line of differentiation. The retroperitoneum and thigh
      represent the most common anatomic locations for both the sarcomas. Despite their
      morphologic similarity, the issue of whether these 2 sarcomas share overlapping
      immunohistochemical and molecular features has not been well studied. We examined
      the expression of the lipogenic tumor-related markers peroxisome proliferator
      activated receptor gamma (PPAR-gamma), CDK4, and MDM2 in 15 cases of DDL and 45
      cases of retroperitoneal/thigh UHGPS. Patients with DDL ranged from 31 to 82
      years (mean 63 y) with a male:female ratio of 5:3. Patients with UHGPS ranged
      from 14 to 80 years (mean 52 y) with a male:female ratio of 3:2. All 15 DDLs
      expressed CDK4 and MDM2 (100%), and 8 of 15 cases expressed PPAR-gamma (53%).
      Twenty-three of 45 (51%) UHGPS expressed at least 1 of these 3 markers. We also
      studied MDM2 and CDK4 gene amplification by fluorescence in situ hybridization in
      28 immunohistochemically positive cases, including 5 DDLs and 23 UHGPSs. All 5
      cases of DDL showed MDM2 and/or CDK4 amplification (100%), whereas 6 of 45 UHGPSs
      showed MDM2 and/or CDK4 amplification (13%). Our results demonstrate that (1) the
      lipogenic tumor markers CDK4 and MDM2 can be used as surrogate
      immunohistochemical markers for the diagnosis of malignant lipomatous tumors with
      high sensitivity; (2) approximately 26% of retroperitoneal/thigh UHGPS cases that
      were positive for PPAR-gamma, CDK4, or MDM2 by immunohistochemistry showed
      characteristic CDK4 and MDM2 gene amplification, suggesting that a subset of
      UHGPS cases represent DDL despite lacking histologic evidence of lipoblasts.

PMID- 19574887
TI  - Pericardial and pleural effusions in congestive heart failure-anatomical,
      pathophysiologic, and clinical considerations.
AB  - Transudative pleural and pericardial effusions are not uncommon in patients with
      congestive heart failure. Pericardial effusion forms only with elevation of the
      right-sided filling pressure in the heart. In patients with biventricular
      failure, there is no evidence that elevated left-sided pressure, in the absence
      of elevated right-sided pressure, can cause a pericardial effusion. Pleural
      effusion forms with acute elevation of the right-sided or the left-sided filling
      pressure in the heart. In patients with congestive heart failure, elevated right
      sided filling pressures are less common than elevated left-sided filling
      pressures, thus, explaining a lower prevalence of pericardial than pleural
      effusions. Pleural effusions in patients with congestive heart failure are
      typically bilateral. However, a unilateral pleural effusion is more commonly seen
      on the right side. Although multiple theories attempt to explain the right-sided
      preponderance of pleural effusion, to date, no mechanism has been universally
      accepted or experimentally proven.

PMID- 19574886
TI  - KIT is an independent prognostic marker for pancreatic endocrine tumors: a
      finding derived from analysis of islet cell differentiation markers.
AB  - Prediction of the biologic behavior of pancreatic endocrine tumor (PET) without
      local invasion or metastasis is often difficult. The 2004 World Health
      Organization (WHO) classification uses size, angioinvasion, mitotic activity, and
      Ki-67 index as prognostic criteria. Recently, cytokeratin 19 (CK19) was shown to
      be another prognostic marker, but the mechanism by which CK19 predicts prognosis
      is unknown. As CK19 is the first cytokeratin expressed in all epithelial cells in
      fetal pancreas, we sought to test expression of other markers of islet cell
      differentiation including KIT, Pdx-1, Pax4, and Pax6 in PET and correlation of
      these markers with clinical behavior. Clinical information and histology was
      reviewed in 97 PETs. All tumors were classified according to WHO criteria and a
      tumor, node, and metastases stage system. Immunohistochemistry was performed
      using antibodies to Ki-67, KIT, CK19, Pdx-1, Pax4, and Pax6. Associations of
      clinicopathologic and immunohistochemical features with prognosis were evaluated
      using Cox proportional hazards regression models. WHO and tumor, node, and
      metastases classifications, mitotic counts and Ki-67 labeling, infiltrative
      border, necrosis, perineural invasion, extrapancreatic extension, tumor size, and
      positive CK19 and KIT expression were significantly associated with death from
      disease in a univariate setting. In multivariate analysis, only WHO criteria and
      KIT expression were shown to be independent. An immunohistochemical
      classification system was derived from a combination of KIT and CK19 expression:
      low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk
      (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly
      different among the 3 groups. These results indicate that KIT is a new and
      independent prognostic marker for PETs. The classification system derived from
      KIT and CK19 was able to predict clinical behavior of PET.

PMID- 19574888
TI  - Comparison of effective use of implanted vascular pedicles for skin flap
      prefabrication: an experimental study.
AB  - Thin, large, well-vascularized, and axial-pattern flaps are often desired in the
      clinical practice of defect reconstruction to maximize esthetic and functional
      results. Flap prefabrication based on the neovascularization development
      following vascular pedicle implantation allows surgeons to create such flaps as
      required. Using different types of implanted vascular pedicles, the aim of the
      study was to identify the most effective and suitable types of pedicles for
      clinical use. Five models of implanted vascular pedicles in Chinchilla Bastard
      rabbits were investigated as follows: model 1, arteriovenous (AV) pedicle with
      end ligation (minimal blood flow in the implanted vascular pedicle); model 2, AV
      pedicle with end anastomosis (new shunt formation between vein and artery stump
      for creating maximal blood flow in the implanted vascular pedicle); model 3,
      purely isolated arterialized venous loop; model 4, purely isolated arterial loop;
      model 5, AV pedicle with end anastomosis (similar to model 2) combined with flap
      expansion. These different types of vascular pedicles were implanted into a
      random-pattern abdominal skin flap as large as 8 x 15 cm. Neovascularization in
      the various prefabricated flaps was evaluated macroscopically, scintigraphically,
      microangiographically, and histologically. A total of 150 prefabricated flaps
      were investigated and randomly assigned to 5 models with 30 flaps each. Each
      model contained 5 groups of 6 flaps corresponding to the various retention times
      of 4, 8, 12, 16, and 20 days after vascular pedicle implantation. Six flaps were
      also designated to the control group. Neovascularization was best in model 5,
      followed by comparable results for models 2, 3, and 4, with the worst results
      found in model 1, especially for the time intervals of 8, 12, and 16 days. Twenty
      days remains the minimal length of time required for matured neovascularization
      in all models (P < 0.05). Models 2 and 3 both appear to be particularly promising
      for clinical application.

PMID- 19574889
TI  - The extended lower trapezius flap for the reconstruction of shoulder tip defects.
AB  - Defects of the shoulder tip expose the glenohumeral and acromioclavicular joints
      and lead to scarring and contractures. Well-vascularized cover is required to
      restore function and appearance. The latissimus dorsi (LD) flap is commonly
      employed but its use affects glenohumeral function, which is undesirable in a
      patient with a shoulder weak from an underlying pathologic condition. We describe
      the extended lower trapezius (Tz) flap for reconstructing the shoulder tip
      defects of 3 patients. This pedicled flap is based on the dorsal scapular artery
      and includes the lower Tz muscle and a long inferior fasciocutaneous extension.
      All flaps healed without complications and all patients regained good shoulder
      function with full range of motion. One patient who developed tumor recurrence
      was treated with re-excision and LD flap reconstruction. The extended lower Tz
      flap based on the dorsal scapular artery is well suited for reconstructing
      shoulder defects. With its fasciocutaneous extension, it has a long arc of
      rotation that is able to reach the shoulder tip. Shoulder morbidity is low as
      only the lower Tz is detached, minimizing disruption to scapulothoracic function.
      And as the LD is spared, glenohumeral function is not affected and the option of
      the LD flap remains available for future use.

PMID- 19574890
TI  - Breast augmentation by autologous fat injection grafting: management and clinical
      analysis of complications.
AB  - Autologous fat is an excellent soft-tissue filler, given its abundance and ease
      of harvest. Nevertheless, the technique is accompanied by postoperative
      complications such as fat necrosis, calcification, and sclerotic nodules. These
      problems directly influence surgical efficacy. Computed tomography or magnetic
      resonance imaging was used to confirm the location of abnormal adipose tissue
      preoperatively. Depending on the characteristics of the lesion, the liquefied fat
      was aspirated or the sclerotic lesion excised. Pressurized dressings were used
      postoperatively for both techniques. Seventeen patients who experienced
      complications after autologous fat injection were treated. Pathologic examination
      of excised samples demonstrated changes including fat necrosis, calcification,
      hyalinization, and fibroplasia. Intramammary autologous fat injection should only
      be used with caution. Selecting suitable indications and correct surgical
      techniques make autologous fat grafting an ideal method for breast augmentation.
      Strictly controlling the injection volume and injecting diffusely in multiple
      layers to allow fat granules to distribute evenly within the breast, are
      effective methods to reduce postoperative complications.

PMID- 19574891
TI  - Expanded narrow subcutaneous-pedicled island forehead flap for reconstruction of
      the forehead.
AB  - To reconstruct the subsequent defects after resection of a unilateral large
      forehead lesion, we devised a revised method, "expanded narrow subcutaneous
      pedicled island forehead flap." After unilateral forehead skin was expanded by a
      tissue expander, the flap was designed on the upper half of the expanded forehead
      skin nourished by the subcutaneous adipomuscular pedicle, including the
      supratrochlear or supraorbital artery. The elevated flap was then transposed or
      rotated 180 degrees toward the defect. The donor site was closed with upward
      advancement of the lower half of the expanded skin. Four patients were treated
      with this method. The flaps survived completely without serious complications,
      and acceptable results were obtained in all patients. This method has the
      advantage of increased freedom of flap design and transfer, providing an
      effective use of unaffected skin, less scars left on the forehead, and less
      formation of the dog-ear compared with the conventional procedure.

PMID- 19574892
TI  - When to use drains in breast reduction surgery?
AB  - We aimed to identify risk factors that may influence surgeons' decision on the
      use of surgical drains in breast reduction surgery. Medical notes of 182 patients
      were reviewed. The mean age of the patients was 38 years and the mean body mass
      index was 25.4 kg/m. Eighty-three percent of the patients had bilateral breast
      reduction. The mean weight of the breast tissue excised was 581 g, with the
      inferior pedicle technique being the most commonly used (52.6%). Factors
      significantly associated with an increased total drain output were older age (>
      50 years, P = 0.001), and larger amount of breast tissue excised (> 500 g, P =
      0.004). Neither operative technique nor body mass index influenced the total
      drain output. We conclude that for patients of over 50 years old and breast
      reductions of more than 500 g, use of a drain should be considered. Younger
      patients and breast reductions of < or = 500 g may not benefit from the use of
      drains.

PMID- 19574893
TI  - Fat necrosis in free DIEAP flaps: incidence, risk, and predictor factors.
AB  - Fat necrosis within a deep inferior epigastric artery perforator flap
      reconstructed breast is considered a minor complication from reconstructive point
      of view, but one that can induce anxiety, inconvenience and concerns about cancer
      recurrence to the oncologist and the patient. A series of 100 consecutive
      unilateral deep inferior epigastric artery perforator flap breast reconstructions
      were reviewed to identify the institutional incidence as well as potential risk
      and predictor factors of fat necrosis. Examination revealed 37 reconstructed
      breasts with palpable firmnesses (described as clinical fat necrosis) and
      ultrasonography and mammography confirmed signs of fat necrosis in 30
      reconstructed breasts. Flaps harvested on a single perforator, obese patients
      with body mass index > or = 30 and revision operations were all statistically
      significant predictors in our statistical model. Postoperative radiotherapy, a
      reconstructed breast volume over 500 mL and a pedicle raised on a single row of
      perforators were statistically significant only after univariate analysis and
      their statistical strength was lost after introducing them with multivariate
      model. This study helped us to further clarify criteria for selection of patients
      undergoing breast reconstruction with flaps from the abdomen.

PMID- 19574894
TI  - Dynamic contour tonometry in eyes after penetrating keratoplasty.

PMID- 19574896
TI  - Where are the older keratoconus patients?

PMID- 19574897
TI  - Deep anterior lamellar keratoplasty to treat microsporidial stromal keratitis.
AB  - PURPOSE: To describe deep anterior lamellar keratoplasty (DALK) as a surgical
      option to treat a case of severe microsporidial stromal keratitis in an
      immunocompetent patient. MATERIALS AND METHODS: This study is a descriptive case
      report. A 42 year-old Pakistani woman had an 8-year history of symptoms in the
      left eye. She had been previously provisionally diagnosed as suspected herpes
      simplex keratitis or Thygeson keratitis. At presentation, her best-corrected
      visual acuity was 20/20 OD and 20/200 OS. Examination of the left cornea revealed
      irregular, central, deep stromal opacification with keratitic precipitates and
      occasional cells in the anterior chamber. Investigations for mycobacteria,
      syphilis, and a tetraplex test were normal; all other
      hematological/biochemistry/virology investigations were normal-she was not found
      to be immunocompromised. RESULTS: A corneal biopsy confirmed microsporidial
      infiltration of the stroma. After intensive medical treatment with topical
      fumagillin and oral albendazole without resolution, DALK was performed with total
      stromal replacement using the big-bubble technique. One year postoperatively, the
      graft remained clear with no evidence of recurrence and best-corrected visual
      acuity was 20/40 OS. CONCLUSIONS: Microsporidial stromal keratitis is rare.
      Conventional surgical treatment for such a condition has been penetrating
      keratoplasty. DALK may be considered an option for visual rehabilitation in these
      cases.

PMID- 19574898
TI  - Immunotactoid microtubular corneal deposits in bilateral paraprotein crystalline
      keratopathy.
AB  - PURPOSE: To report an ultrastructurally distinct form of paraprotein crystalline
      keratopathy. METHODS: Three corneas submitted from a single patient including one
      native cornea from each eye and a failed corneal graft from the right eye. Light
      microscopy, immunohistochemistry, immunofluorescence, and transmission electron
      microscopic examination were performed. RESULTS: The transmission electron
      microscopy showed "immunotactoid" extracellular microtubular deposits measuring
      >30 nm in diameter with a central lucent core. CONCLUSIONS: Immunotactoid
      keratopathy is a distinct type of paraprotein crystalline keratopathy associated
      with a monocolonal immunoglobulin G kappa light chain (IgGk) protein. Larger case
      series are needed to determine the clinical significance of this entity.

PMID- 19574899
TI  - Donor-related Candida keratitis after Descemet stripping automated endothelial
      keratoplasty.
AB  - PURPOSE: To report 2 cases of donor-to-host transmission of Candida albicans
      interface keratitis after Descemet stripping automated endothelial keratoplasty
      (DSAEK). METHODS: We performed clinical and microbiologic examinations on 2
      patients who underwent DSAEK for pseudophakic corneal edema. RESULTS: Two
      patients underwent uneventful DSAEK surgery using corneal tissue from the same
      donor. The donor corneoscleral rims were cultured at the time of surgery and both
      rims subsequently grew C. albicans and Candida glabrata. Approximately 5 weeks
      after surgery, infiltrates were noted in the DSAEK interface in both of these
      patients. Despite treatment with antifungal therapy, the Candida keratitis was
      unable to be controlled medically and required surgical intervention in each
      case, after which there was no recurrence of infection. CONCLUSIONS: Candida
      interface keratitis can occur after DSAEK. These 2 cases emphasize the importance
      of donor corneoscleral rim cultures, especially with the increase in lamellar and
      endothelial keratoplasty, which can make such interface infections more difficult
      to diagnose and treat. Patients with fungal positive donor corneal rim cultures
      should be prophylactically treated with antifungal therapy.

PMID- 19574900
TI  - Therapeutic effect of topical 5-fluorouracil in conjunctival squamous carcinoma
      is associated with changes in matrix metalloproteinases and tissue inhibitor of
      metalloproteinases expression.
AB  - PURPOSE: To evaluate matrix metalloproteinases (MMP)-2, MMP-9, and tissue
      inhibitor of metalloproteinase (TIMP)-1 expression in a case of conjunctival
      intraepithelial squamous cell carcinoma (SCC) treated with topical 5-fluorouracil
      (5-FU) chemotherapy. METHODS: Clinicopathologic case report. RESULTS: A 71-year
      old male patient presented with an intraepithelial conjunctival SCC. Because of a
      recurrence, he was placed on topical 5-FU for 4 weeks that ultimately led to a
      complete resolution of the disease. Conjunctival biopsies, impression cytologies,
      and tear samples were taken from the mass and the contralateral healthy eye. An
      overexpression of MMP-2, MMP-9, and TIMP-1 was observed in the tumor by
      immunohistochemistry. Clinical resolution of the neoplasm obtained using topical
      5-FU was accompanied by a reduction in the expression of MMP-2, MMP-9, and TIMP-1
      in tears and dysplastic conjunctival epithelium. CONCLUSIONS: In our case report,
      we have shown that gelatinase and TIMP-1 are unregulated in conjunctival SCC and
      can be monitored as a marker of response to topical chemotherapy. Further studies
      are required to define the role of MMPs in growth and resolution of ocular
      tumors.

PMID- 19574901
TI  - Conjunctival impression cytology for the diagnosis, follow-up, and treatment in a
      patient with severe keratoconjunctivitis caused by alkali injury.
AB  - PURPOSE: To report a case of severe keratoconjunctivitis after chemical exposure
      that was treated by a conjunctival-limbal autograft transplantation according to
      conjunctival impression cytology (CIC) results. METHODS: A 48-year-old woman was
      diagnosed with a severe keratoconjunctivitis developed after exposure to a
      mixture of abrasive cleaning agents. Based on CIC results, decision to perform a
      limbal-conjunctival autotransplantation from the contralateral eye was taken
      after conventional topical treatment failed to improve symptoms. Polyethersulfone
      papers were used to take samples from the superior and inferior bulbar
      conjunctiva of affected and contralateral eyes, and Periodic acid Schiff's (PAS)
      staining was used to reveal the status of goblet cell (GC) population of the
      conjunctiva. RESULTS: Tearing, burning sensation, keratitis, squamous metaplasia,
      and GC improved noticeably, as observed by CIC, after autotransplantation.
      CONCLUSIONS: CIC helped on the diagnosis, treatment decision, and follow-up of a
      patient severely affected by alkali exposure by checking the status of GC in the
      conjunctiva. Limbal-conjunctival autotransplantation decision was taken and
      performed consequently, and a significant improvement was observed through a
      follow-up by CIC.

PMID- 19574902
TI  - The comparison of femtosecond laser-assisted penetrating keratoplasty with
      conventional surgery in terms of endothelial safety: ex vivo study using porcine
      eyes.
AB  - PURPOSE: To evaluate the effect of using femtosecond (FS) laser technology for
      penetrating keratoplasty (PK) in terms of corneal graft endothelial
      ultrastructure and viability in porcine eyes. METHODS: Thirty-two freshly
      enucleated porcine eyes were divided into 4 equal groups (n = 8): group 1,
      incomplete penetration using the FS laser (a 100 microm-depth from the
      endothelial side remained); group 2, complete penetration using the FS; group 3,
      trephination using a vacuum trephine until the aqueous humor appeared; group 4,
      no treatment (control group). For groups 1 and 2, side cuts were performed using
      a 60-kHz FS laser (IntraLase FS Laser, Abbot Medical Optics, Abbott Park, IL).
      Preoperative ultrasound pachymetry was used to make measurements at 5 positions.
      Scanning electron microscopy (SEM) was used to determine morphological changes,
      and light microscopy with Alizarin red staining was used to determine the amount
      of cell death. RESULTS: Preoperative corneal thicknesses were similar for all
      groups. All 4 groups showed similar corneal endothelial cell morphology and
      viability at the graft center (P = 0.15, Kruskal-Wallis test). At the graft
      border, endothelial cell damage was minor in group 1, moderate in group 2, and
      most severe and diffuse in group 3 (P = 0.009, Kruskal-Wallis test). CONCLUSIONS:
      FS laser use is safe for the endothelium at the graft center and has less harmful
      effects on the endothelium at the incision area than does conventional
      trephination. Therefore, FS laser-assisted corneal grafts with complete
      penetration seems to be the optimum choice for preserving endothelial cells
      during PK.

PMID- 19574903
TI  - The Boston Keratoprosthesis: comparing corneal epithelial cell compatibility with
      titanium and PMMA.
AB  - PURPOSE: To determine in vitro whether titanium is superior in corneal cell
      compatibility to standard polymethyl-methacrylate (PMMA) for the Boston
      Keratoprosthesis (KPro). METHODS: Human corneal-limbal epithelial (HCLE) cells
      were cultured 24, 48, 72, 96, 120, 144, or 168 hours in culture plates alone
      (controls) or with PMMA or titanium discs. Experiments were performed in
      triplicate and repeated (final n = 6). To determine if a soluble, toxic factor is
      emitted from materials, concurrent experiments at 48 and 144 hours were performed
      with discs placed in Transwell Supports, with HCLE cells plated beneath. As an
      additional test for soluble factors, cells were incubated 24 hours with disc
      conditioned media, and number of viable cells per well was quantified at each
      timepoint by proliferation assay. To determine if delayed cell proliferation was
      attributable to cell death, HCLE cell death was measured under all conditions and
      quantified at each timepoint by cytotoxicity assay. The effects of material on
      HCLE cell proliferation over time was determined by repeated measures ANOVA. P <
      0.05 was statistically significant. RESULTS: HCLE cell proliferation was greater
      in wells with titanium discs compared to PMMA. Differences between the test discs
      and control non-disc cocultures were statistically significant over time for both
      cell proliferation (P = 0.001) and death (P = 0.0025). No significant difference
      was found using Transwells (P = 0.9836) or disc-conditioned media (P = 0.36).
      CONCLUSION: This in vitro HCLE cell model demonstrates significantly increased
      cell proliferation and decreased cell death with cell/titanium contact compared
      to cell/PMMA contact. Moreover, differences are unlikely attributable to a
      soluble factor. Prospective in vivo analysis of the two KPro biomaterials is
      indicated.

PMID- 19574904
TI  - Exclusion of positional candidate gene coding region mutations in the common
      posterior polymorphous corneal dystrophy 1 candidate gene interval.
AB  - PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is an autosomal-dominant
      disorder of the corneal endothelium associated with visually significant corneal
      edema and glaucoma. Statistical genetic analysis of 4 families with PPCD has
      demonstrated linkage to a 2.4 cM common support interval on chromosome 20
      bordered by the markers D20S182 and D20S139. We sought to identify the genetic
      basis of PPCD linked to chromosome 20 (PPCD1) by screening the 26 positional
      candidate genes between these markers in a family previously mapped to the PPCD1
      region. METHODS: The coding regions of the 26 positional candidate genes mapped
      to the common PPCD1 support interval were amplified and sequenced in affected and
      unaffected individuals from a family previously linked to the PPCD1 locus. Nine
      other genes positioned just outside of the common PPCD1 support interval but
      within the autosomal-dominant congenital hereditary endothelial dystrophy
      interval were also screened. RESULTS: Four DNA sequence variants in 3 of the
      positional candidate genes demonstrated complete segregation with the affected
      phenotype: p.Thr109Thr (rs6111803) in OVOL2, p.Arg56Gln (novel variant-RPSnovel)
      in RPS19P1, and p.Thr85Thr (rs1053834) and p.Pro99Ser (rs1053839) in C20orf79.
      Each of these 4 sequence variants demonstrated significant linkage with the
      affected phenotype in this family (P = 2.5 x 10 for RPSnovel, rs1053834 and
      rs1053839; P = 8.6 x 10 for rs6111803). However, we also identified each of these
      4 sequence variants in > or = affected control individuals. The haplotype on
      which the disease-causing mutation is segregating was found to have a population
      frequency of 4.2% in the CEPH HapMap trios. Although a number of other previously
      described and novel single nucleotide polymorphisms were identified in the 35
      positional candidate genes located within the PPCD1 and congenital hereditary
      endothelial dystrophy intervals, none segregated with the affected phenotype.
      CONCLUSIONS: We report the absence of a presumed pathogenic coding region
      mutation in the common PPCD1 support interval. Although minor alleles of 4 single
      nucleotide polymorphisms were identified that segregated with the affected
      phenotype, the relatively high frequency of each minor allele in the general
      population indicates that none is a candidate for the causal variant for PPCD.
      Instead, the causal variant is most likely a coding region deletion or a variant
      in a noncoding region of the PPCD1 common support interval.

PMID- 19574905
TI  - Top-hat shaped corneal trephination for penetrating keratoplasty using the
      femtosecond laser: a histomorphological study.
AB  - PURPOSE: To evaluate a novel technique for penetrating keratoplasty (PK) with the
      use of a new software algorithm for the femtosecond laser, designed to create
      penetrating cuts in a top hat configuration. DESIGN: Consecutive
      histomorphological case series. PATIENTS AND METHODS: Twelve eyes of 12 patients
      underwent penetrating keratoplasty by means of a 60-kHz femtosecond laser
      (IntraLase, Irvine, California) with a software specifically developed for
      corneal surgery. Of the 12 patients, the reason for keratoplasty was keratoconus
      in 4 patients, bullous keratopathy in 6 patients, keratotorus in 1 patient, and
      status post chemical burn in 1 patient. A new software was used to create
      penetrating cuts in a top-hat-shaped configuration. In all cases, cutting
      parameters were identical in all donor and corresponding host corneas: 7.0 mm
      diameter of the anterior side cut, 8.5-8.7 mm diameter of the posterior side cut,
      and a depth of 300 microm for the lamellar cut. In all cases, a complete
      penetrating cut with the laser in the host cornea was not intended
      intraoperatively. Complete penetration was performed subsequently and manually
      with a diamond knife because of logistic conditions. Trephined corneoscleral
      rings and button corneas were analyzed macroscopically and histologically to
      determine cut quality. RESULTS: All procedures were performed without any
      complications. With application of appropriate combinations of pulse energy and
      spacing, trephination took less than 200 seconds. Macroscopic examination and
      histology of donor and recipient specimens showed a straight, smooth cut with
      perpendicular edges in all donor buttons. No corneal edema and no visible damage
      to the keratocyte nuclei were found. At the region of manual dissection, a small
      stromal tissue-tag was present in parts of the circumference in all donor
      buttons. No evidence of any cut complication was noted. CONCLUSIONS: Top-hat
      shaped penetrating keratoplasty using the IntraLase femtosecond laser enables a
      quick and sufficient trephination of both human donor and host corneas. It
      creates favorable histomorphological results with regard to cut quality of the
      donor and host corneas.

PMID- 19574906
TI  - The relationship between dry eye symptoms and lipid layer thickness.
AB  - PURPOSE: (1) To investigate the relationship between dry eye symptoms and lipid
      layer thickness (LLT) in patients presenting for routine eye examination and (2)
      to consider the practicality of interferometry in a clinical practice. METHODS:
      Patients presenting consecutively for routine eye examinations were recruited (n
      = 137, age range = 18-60 years, mean = 41.7 +/- 15.5 years, 102 females and 35
      males). Patients were required to complete the Standard Patient Evaluation of Eye
      Dryness (SPEED) questionnaire after which their LLT was evaluated using a new
      interferometer (Ocular Surface Interferometer). Patients were assigned to 1 of 3
      symptom categories: no symptoms (SPEED = 0), mild to moderate symptoms (SPEED = 1
      9), and severe symptoms (SPEED > or = 10). Categorical analysis (contingency
      table) and linear regression were performed on the data. RESULTS: For patients
      with severe dry eye symptoms, 74% had an LLT < or =60 nm. Conversely, 72% of
      patients with no dry eye symptoms had an LLT of > or =75 nm (contingency table,
      chi = 12.63, df = 2, p = 0.0018). Furthermore, a linear regression of LLT and
      SPEED score reveal a significant linear relationship (as LLT increases, SPEED
      score decreases; p = 0.0014). CONCLUSIONS: (1) The data indicate that
      approximately 3 of 4 patients reporting severe symptoms have relatively thin
      lipid layers of 60 nm or less, whereas approximately 3 of 4 patients without
      symptoms have relatively thick lipid layers of 75 nm or more. Thus, the presence
      of dry eye symptoms significantly increases the likelihood of a relatively thin
      lipid layer. LLT seems to correlate better to symptoms, especially severe
      symptoms, than other reported correlations with objective clinical tests for dry
      eye disease. (2) Interferometry has the potential to be a practical and useful
      addition to clinical practice.

PMID- 19574907
TI  - Optical image quality and visual performance for patients with keratitis.
AB  - PURPOSE: To evaluate the optical image quality, using 2 optical devices (an
      aberrometer and a double-pass device), and visual performance [contrast
      sensitivity function (CSF)] in patients with keratitis and after resolution of
      the disease. METHODS: Twenty subjects with keratitis (18 patients with unilateral
      keratitis and 2 patients with bilateral keratitis) were included in this study.
      We also took measurements in healthy fellow eyes for comparison. Ten patients
      were studied before and after the resolution of keratitis. Objective data were
      gathered by aberrometry (ocular higher order, spherical, and coma aberrations)
      and the Strehl ratio, a parameter derived from the double-pass device that
      included information on diffraction, ocular aberrations, and scattering. The CSF
      was also measured for all the patients. RESULTS: Ocular higher order, spherical,
      and coma aberrations in keratitis eyes were significantly (P < 0.05) higher than
      those in healthy fellow eyes. The Strehl ratio indicates a worse optical quality
      for keratitis eyes being significantly (P < 0.05) lower than the Strehl ratio for
      healthy fellow eyes. CSF for keratitis eyes was also significantly lower than
      that for the healthy eyes (P < 0.05). Data for keratitis eyes after the
      resolution of the disease showed a significant increase in the optical function
      and visual performance but, after treatment, continued to suffer significant (P <
      0.05) impairment in the optical quality of the affected eyes compared with the
      healthy fellow eyes. CONCLUSIONS: Devices to measure optical image quality and
      the CSF enable the characterization of the optical quality and visual performance
      in patients with keratitis, showing a significant decline in optical quality and
      visual performance during keratitis and an improvement after the resolution of
      the pathology.

PMID- 19574908
TI  - Examination of Staphylococcus aureus on the ocular surface of patients with
      catarrhal ulcers.
AB  - PURPOSE: The purpose of this study was to investigate the role of Staphylococcus
      aureus in the onset of ocular catarrhal ulcers. METHODS: We examined the
      colonization by S. aureus of the ocular surface (conjunctival sac, upper and
      lower lid margins) of 3 patients with catarrhal ulcers and analyzed the S. aureus
      isolates by pulsed-field gel electrophoresis. RESULTS: S. aureus organisms were
      found on the lid margin of all eyes affected by catarrhal ulcers. The
      contralateral eye without ulcers harbored S. aureus exhibiting a pulsed-field gel
      electrophoresis pattern identical to that of the affected eye. CONCLUSIONS:
      Although S. aureus on the lid margin plays an important role in the onset of
      catarrhal ulcers, its presence is one among several risk factors.

PMID- 19574909
TI  - Comparison of keratocyte density between keratoconus, post-laser in situ
      keratomileusis keratectasia, and uncomplicated post-laser in situ keratomileusis
      cases. A confocal scan study.
AB  - PURPOSE: To compare keratocyte density in corneal stromal layers in keratoconus,
      post-laser in situ keratomileusis (LASIK) keratectasia, uncomplicated post-LASIK
      cases, and normal unoperated corneas by confocal scan. METHODS: Thirty-one
      unscarred corneas from 22 patients with keratoconus, 24 clear corneas from 17
      cases with post-LASIK keratectasia, 12 corneas from 7 uncomplicated post-LASIK
      cases, and 26 corneas from 13 normal unoperated cases were evaluated by using
      confocal scan. None of the cases were contact lens wearers. Keratocyte densities
      were determined in 3 stromal layers in each cornea and compared with densities in
      the corresponding layers of normal unoperated corneas. Cell densities in
      different corneal layers were also compared in each group. RESULTS: In overall,
      93 eyes from 59 patients with mean age of 30 +/- 7.3 years were enrolled. There
      was no difference in mean keratocyte density at 3 stromal layers between
      keratoconic and normal unoperated corneas. In post-LASIK keratectasia, keratocyte
      density in the anterior and posterior stromal layers was significantly lower than
      that in normal unoperated group. In uncomplicated post-LASIK cases, the
      keratocyte density at 3 stromal layers was lower than that in normal unoperated
      group. No difference in keratocyte density was found between post-LASIK
      keratectasia and uncomplicated post-LASIK cases. Furthermore, in post-LASIK
      keratectasia, there was a meaningful difference in keratocyte density between the
      anterior and posterior and between the middle and posterior stromal layers; such
      a difference was not observed in the uncomplicated post-LASIK cases. CONCLUSIONS:
      Mean keratocyte density in post-LASIK keratectasia and uncomplicated post-LASIK
      cases was lower than that in normal unoperated group. Given the different
      distribution of keratocytes between the stromal layers in the 2 LASIK groups,
      there was a nonhomogenous distribution of keratocytes in stromal layers in post
      LASIK keratectasia. A homogenous distribution of keratocytes in uncomplicated
      post-LASIK cases may be a factor in prevention of corneal ectasia.

PMID- 19574910
TI  - Conjunctival impression cytology by using a thermosensitive adhesive: polymerized
      N-isopropyl acrylamide.
AB  - PURPOSE: We aimed to evaluate a new technique using a thermosensitive glue
      coating for impression cytology of the ocular surface. METHODS: We prepared
      plasma polymerized N-isopropyl acrylamide (pNIPAM)-coated parylene C
      (poly(monochloro-p-xylylene)) films to obtain cytological samples from the
      conjunctival surface. We compared this new technique with the conventional
      nitrocellulose paper method in regards to the quality of impression cytology and
      quantity of the cells in 30 postmenauposal women with dry eye complaints.
      RESULTS: The cellular material was adequate for evaluation in 28 (93%) of 30 eyes
      in pNIPAM-coated parylene group and in 18 (60%) of 30 eyes in the nitrocellulose
      group (P = 0.0002). pNIPAM-coated parylene technique was superior to the
      nitrocellulose technique regarding the mean number of cells per microscopic field
      (P = 0.00003), integrity of the cells (P = 0.00001), and cellular preservation (P
      = 0.0002). CONCLUSION: The number of cells and the quality scores were
      significantly higher in the pNIPAM-coated impression cytology technique than the
      nitrocellulose method.

PMID- 19574911
TI  - Comparison of the changes in corneal biomechanical properties after
      photorefractive keratectomy and laser in situ keratomileusis.
AB  - PURPOSE: To compare the postoperative biomechanical properties of the cornea
      after photorefractive keratectomy (PRK) and after laser in situ keratomileusis
      (LASIK) in eyes with myopia. METHODS: We retrospectively examined 27 eyes of 16
      patients undergoing PRK and 31 eyes of 16 patients undergoing LASIK for the
      correction of myopia. Corneal hysteresis (CH) and corneal resistance factor (CRF)
      were measured with Ocular Response Analyzer before and 3 months after surgery. We
      also investigated the relationship between these biomechanical changes and the
      amount of myopic correction. RESULTS: The CH was decreased significantly from
      10.8 +/- 1.3 (mean +/- SD) mmHg to 9.2 +/- 1.6 mmHg after PRK (P < 0.001), and
      from 10.8 +/- 1.4 mmHg to 8.6 +/- 0.9 mmHg after LASIK (P < 0.001). The CRF was
      also decreased significantly, from 10.3 +/- 1.5 mmHg to 8.4 +/- 1.8 mmHg after
      PRK (P < 0.001), and from 10.3 +/- 1.5 mmHg to 7.7 +/- 1.3 mmHg after LASIK (P <
      0.001). The amount of decrease in CH and CRF was significantly larger after LASIK
      than after PRK (P = 0.04). There was a significant correlation between the amount
      of myopic correction and changes in biomechanical properties after PRK (r = 
      0.61, P < 0.01 for CH, r = -0.41, P < 0.05 for CRF) and LASIK (r = -0.37, P <
      0.05 for CH, r = -0.45, P < 0.05 for CRF). CONCLUSIONS: Both PRK and LASIK can
      affect the biomechanical strength of the cornea depending on the amount of myopic
      correction. The amount of biomechanical changes is larger after LASIK than after
      PRK. From a biomechanical viewpoint, PRK may be a less invasive surgical approach
      for the correction of myopia than LASIK.

PMID- 19574912
TI  - Steroid-induced intraocular pressure elevation or glaucoma after penetrating
      keratoplasty in patients with keratoconus or Fuchs dystrophy.
AB  - PURPOSE: The aim of the present study was to evaluate the frequency of steroid
      induced intraocular pressure (IOP) elevation and/or glaucoma in patients with
      keratoconus (KCN) compared with patients with Fuchs endothelial dystrophy after
      penetrating keratoplasty (PK). METHODS: A retrospective review of the medical
      records of patients with KCN or Fuchs dystrophy, who underwent PK and were
      examined on the Cornea Service, Wills Eye Institute, was performed. IOP
      measurements were recorded preoperatively; postoperative first month and maximal
      IOP measurements between 1 and 3 months, 4 and 6 months, 7 and 12 months, 1 and 2
      years, 2 and 3 years, and 3 and 4 years were noted. Steroid-induced IOP elevation
      and/or glaucoma were grouped into 5 different categories; an increase in IOP of
      at least 5 or 10 mm Hg over the preoperative baseline and also IOP > or =22, 30,
      and 40 mm Hg. Addition of glaucoma medications and/or characteristic glaucomatous
      optic disc and visual field changes were also assessed. RESULTS: A total of 100
      patients with KCN and 58 patients with Fuchs dystrophy were included in this
      study. The overall frequency of steroid-induced IOP elevation after PK was 73% in
      the KCN group and 60.3% in the Fuchs dystrophy group. The frequency of IOP
      elevation of at least 5 or 10 mm Hg over the preoperative baseline were 72% and
      24% in KCN group and 56.9% and 20.7% in the Fuchs dystrophy group, respectively.
      The frequency of IOP elevation > or =22 or > or =30 mm Hg was 22% and 6% in the
      KCN group and 29.3% and 1.7% in the Fuchs dystrophy group, respectively. There
      was one patient in the KCN group who had IOP >40 mm Hg. There was no difference
      between the groups in terms of frequency of IOP elevation (P > 0.05 for all).
      Glaucomatous visual field defect was detected in 4 patients in the KCN group and
      only one patient in the Fuchs dystrophy group. Despite the maximum medical
      therapy, 2 patients in the KCN group underwent glaucoma surgery and none in the
      Fuchs dystrophy group. CONCLUSION: Steroid-induced IOP elevation or glaucoma
      after PK is not unusual in eyes with KCN or Fuchs dystrophy. Careful and ongoing
      observation of IOP throughout the prolonged follow-up period is recommended for
      these individuals with prompt attention to IOP treatment as indicated.

PMID- 19574913
TI  - Treatment of superior limbic keratoconjunctivitis with a large-diameter contact
      lens and Botulium Toxin A.
AB  - PURPOSE: To evaluate the effect of a large-diameter (16-20 mm) hydrogel contact
      lens (CL) or an injection of Botulinum Toxin A to Riolan muscle for the treatment
      of superior limbic keratoconjunctivitis (SLK). METHODS: Eight eyes from 8
      patients were fitted with large-diameter CL for 7 days. The clinical improvement
      and changes of fluorescein and rose bengal staining were examined on the day of
      diagnosis and 3, 7, 14, and 30 days after the CL was fitted. Three eyes showing
      symptoms of recurrence of SLK within 1 month after removal of the CL and 2 eyes
      with complications related to CL were treated with an injection of Botulinum
      Toxin A to pretarsal orbicularis muscle, Riolan. The changes of symptoms and
      vital stains were also evaluated on day 7 and 1, 2, 3, and 6 months after the
      injection. RESULTS: The mean age was 48 +/- 13.5 years, and the group consisted
      of 6 females and 2 males. Dry eye syndrome and horizontal conjunctival
      corrugation were found in all 8 patients, superior conjunctivochalasis in 5
      patients, and floppy eyelid syndrome in 2 patients. Complete resolution after
      more than 1 month with CL only was seen in 3 eyes (37.5%). Clinical symptoms
      improved in 4.62 days and vital staining in 10.75 days after fitting of the CL.
      Superficial punctuate keratopathy related to CL occurred in 3 eyes (37.5%). Five
      eyes (62.5%) that were treated with botulinum showed distinct improvement within
      7 days after the injection, and the effect was maintained for 2-7 months.
      CONCLUSIONS: The fitting of large-diameter CL can be considered for the treatment
      of acute severe symptoms of SLK for a short time. An injection of Botulinum toxin
      to the Riolan muscle can effectively and rapidly resolve the symptoms associated
      with SLK, and its effect of maintenance was a mean of 4 months.

PMID- 19574914
TI  - Gundersen flaps in the management of ocular surface disease in an Asian
      population.
AB  - PURPOSE: To evaluate the indications, complications, and long-term outcomes with
      the use of a Gundersen flap for the treatment of various ocular surface
      conditions in an Asian population. DESIGN: Retrospective case series. STUDY
      SUBJECTS: Twenty-five eyes of 25 subjects who had undergone conjunctival flap
      surgery performed from 1999 to 2004 at the Singapore National Eye Centre.
      METHODS: Review of case records for indications and outcomes of patients
      undergoing Gundersen flap surgery. MAIN OUTCOME MEASURES: Surgical success was
      defined as attainment of a stable ocular surface with resolution of symptoms and
      no flap retraction or dehiscence resulting in reexposure of the corneal surface.
      Complications to be noted included infection, progression of the inflammatory or
      infectious disease process beneath the flap, flap loss from epithelial ingrowth,
      and epithelial cyst formation. RESULTS: Surgical success was achieved in all
      eyes. Intraoperative and postoperative complications were encountered in 6
      patients (24%). One case had a buttonhole, 3 cases had partial flap retractions,
      and 2 had epithelial inclusion cysts. CONCLUSIONS: The Gundersen flap is still an
      important procedure and should be considered as a means of stabilizing globe
      integrity in the management of cases of severe ocular surface disease,
      particularly when visual potential is poor.

PMID- 19574916
TI  - Corneal sensitivity and slit scanning in vivo confocal microscopy of the subbasal
      nerve plexus of the normal central and peripheral human cornea.
AB  - PURPOSE: To determine the subbasal nerve density and tortuosity at 5 corneal
      locations and to investigate whether these microstructural observations correlate
      with corneal sensitivity. METHOD: Sixty eyes of 60 normal human subjects were
      recruited into 1 of 3 age groups, group 1: aged <35 years, group 2: aged 35-50
      years, and group 3: aged >50 years. All eyes were examined using slit-lamp
      biomicroscopy, noncontact corneal esthesiometry, and slit scanning in vivo
      confocal microscopy. RESULTS: The mean subbasal nerve density and the mean
      corneal sensitivity were greatest centrally (14,731 +/- 6056 microm/mm and 0.38
      +/- 0.21 millibars, respectively) and lowest in the nasal mid periphery (7850 +/-
      4947 microm/mm and 0.49 +/- 0.25 millibars, respectively). The mean subbasal
      nerve tortuosity coefficient was greatest in the temporal mid periphery (27.3 +/-
      6.4) and lowest in the superior mid periphery (19.3 +/- 14.1). There was no
      significant difference in mean total subbasal nerve density between age groups.
      However, corneal sensation (P = 0.001) and subbasal nerve tortuosity (P = 0.004)
      demonstrated significant differences between age groups. Subbasal nerve density
      only showed significant correlations with corneal sensitivity threshold in the
      temporal cornea and with subbasal nerve tortuosity in the inferior and nasal
      cornea. However, these correlations were weak. CONCLUSIONS: This study
      quantitatively analyzes living human corneal nerve structure and an aspect of
      nerve function. There is no strong correlation between subbasal nerve density and
      corneal sensation. This study provides useful baseline data for the normal living
      human cornea at central and mid-peripheral locations.

PMID- 19574915
TI  - Long-term outcome of combined penetrating keratoplasty with scleral-sutured
      posterior chamber intraocular lens implantation.
AB  - PURPOSE: To evaluate the long-term outcomes of combined penetrating keratoplasty
      (PKP) with scleral-sutured posterior chamber intraocular lens (PC-IOL)
      implantation. METHODS: Medical records from patients with aphakic and
      pseudophakic bullous keratopathy were retrospectively reviewed for preoperative
      indications and postoperative results of 105 consecutive patients (105 eyes) who
      underwent combined PKP and scleral-sutured PC-IOL implantation over a 13-year
      period. Main outcomes measures were graft survival rate, visual acuity, and
      intraoperative and postoperative complications. RESULTS: The principal
      indications for PKP were pseudophakic and aphakic corneal edema. Graft survival
      rates were 97% at 1 year, 91% at 2 years, 75% at 5 years, and 68% at 7 years.
      Mean postoperative follow-up was 44.8 +/- 37.0 months (range 1-156). The best
      corrected visual acuity improved at least 1 line on the Snellen chart in 59.0% of
      the patients, with 42.9% of the eyes achieving acuities of 20/100 or better.
      Postoperative complications included new glaucoma in 21.4%, worsening of pre
      existing glaucoma in 28.6%, cystoid macular edema in 17%, infectious
      endophthalmitis in 3.8%, and intraocular lens dislocation in 1.9%. No
      intraoperative complications were encountered. CONCLUSIONS: PKP combined with
      scleral-sutured PC-IOL implantation can achieve acceptable outcomes with a low
      rate of intraocular lens dislocation, but may be associated with significant
      short and long-term complications.

PMID- 19574917
TI  - Staining patterns in dry eye syndrome: rose bengal versus lissamine green.
AB  - PURPOSE: To evaluate and compare corneal staining patterns of lissamine green
      (LG) versus rose bengal (RB) in patients with dry eye syndrome. Secondary
      objectives included addressing patient's comfort after instillation and to
      correlate disease severity with staining patterns. METHODS: Randomized,
      comparative, crossover series. Patients with previous diagnosis of mild to
      moderate dry eye syndrome were divided in 2 groups regarding dye instillation
      order (group A: RB first; group B: LG first). Both dyes were applied in regular
      intervals, and a staining score (van Bijsterveld scale) was used to correlate and
      compare the results. Disease severity was determined by the Ocular Surface
      Disease Index. Comfort was evaluated by patient's answer in an objective
      questionnaire. RESULTS: Sixty eyes of 30 consecutive patients (24 females and 6
      males) were included. There was no statistical difference between groups
      regarding disease severity, sex, or age. LG and RB showed good clinical
      correlation in both groups (group A: r = 0.939, P < 0.001; group B: r = 0.915, P
      < 0.001). LG was better tolerated than RB (P = 0.003 in both groups). Overall, we
      found a low statistical correlation between disease severity and staining scores.
      CONCLUSIONS: Both LG and RB showed similar staining patterns. RB was found to
      provide greater patient discomfort. There was no correlation between disease
      severity (addressed by the ocular surface disease index questionnaire) and
      staining patterns (measured by the van Bijsterveld scale).

PMID- 19574918
TI  - Air-assisted manual deep anterior lamellar keratoplasty for treatment of herpetic
      corneal scars.
AB  - PURPOSE: To evaluate the prognosis and results of deep anterior lamellar
      keratoplasty (DALK) by intrastromal air injection for corneal opacity after
      herpes simplex keratitis. METHODS: Retrospective analysis of 12 eyes of 12
      patients, with minimum follow-up of 15 months. To reduce the risk of perforation
      in scarred corneas, DALK was performed by a more superficial intrastromal air
      injection, avoiding the formation of a big bubble, followed by manual dissection
      to a near-Descemetic level. Oral acyclovir (1200 mg daily) was started 1 month
      before surgery and continued for 5 months, then tapered to 800 mg daily for
      further 6 months. RESULTS: DALK was successfully completed in all 12 eyes. No
      cases of rejection or recurrent keratitis were observed. One case with cataract
      and diabetic retinopathy is excluded from statistics. At 15 months, the mean
      improvement of best spectacle-corrected visual acuity was 0.51 (SD 0.19; range
      0.3-0.9) (P < 0.05). In the 7 eyes in which preoperative spherical equivalent was
      known, a mean myopic shift of 2.38 diopters (D) (SD 1.15 D) was observed (P <
      0.05). Mean postoperative defocus equivalent was 5.89 D (SD 2.51 D). Mean
      postoperative refractive astigmatism was 2.66 D (SD 0.99 D; range 1.5-5 D).
      Moderate interface opacity was transitorily observed in 4 cases for 2-6 months.
      In the patient with cataract, cataract extraction was successfully completed
      without complications. CONCLUSION: DALK for postherpetic leukoma had a safe
      intraoperative profile and resulted in a significant visual recovery, with a 2-D
      myopic shift.

PMID- 19574919
TI  - Measurements of intraocular pressure by Goldmann tonometry, Tonopen XL, and the
      transpalpebral tonometer, TGDc-01, after penetrating keratoplasty: a comparativye
      study.
AB  - PURPOSE: The aim of this study was to compare intraocular pressure (IOP)
      measurements obtained by Goldmann tonometry (GT), the Tonopen XL, and a new
      transpalpebral tonometer, TGDc-01, in eyes that had undergone penetrating
      keratoplasty (PKP). METHODS: IOP was measured in post-PKP eyes by means of GT,
      Tonopen XL, and TGDc-01. Central corneal thickness measurements were also
      obtained for all eyes. RESULTS: Forty-five eyes of 43 patients were enrolled in
      the study. The mean IOP difference (+/-SD) was -0.42 +/- 5.83 mm Hg between GT
      and Tonopen and 3.20 +/- 7.55 mm Hg between GT and TGDc-01. The correlation
      coefficient was 0.84 between GT and Tonopen XL (P < 0.001) and 0.71 between GT
      and TGDc-01 (P < 0.001). Overall 2-way analysis of variance between the means
      showed no significant differences between the 3 devices (P = 0.077). CONCLUSION:
      A closer agreement was found between GT and Tonopen XL in post-PKP eyes. TGDc-01
      yielded lower IOP readings than the other 2 devices. It remains uncertain whether
      this new transpalpebral tonometer is simply inaccurate or whether avoiding
      contact with the corneal graft by measuring IOP through the eyelid enables it to
      provide more accurate IOP readings than those obtained by transcorneal
      techniques.

PMID- 19574921
TI  - Strategies to enhance cardiovascular disease prevention in patients with
      diabetes.
AB  - PURPOSE OF REVIEW: To describe current strategies to enhance cardiovascular
      disease (CVD) prevention in patients with abnormal glucose regulation. RECENT
      FINDINGS: Early detection of glucose abnormalities and a multifactorial approach
      to all modifiable risk factors are effective strategies to reduce the burden of
      CVD in patients with diabetes mellitus. Available evidence suggests that an
      overly aggressive approach to lowering of glucose may contribute to
      complications; different hypoglycaemic agents may vary in the likelihood with
      which their use may give rise to complications. Thus, a decrease of glucose
      levels below that recommended in available guidelines is not recommended.
      SUMMARY: Given its increasing prevalence and its substantial concomitant risk for
      CVD, diabetes mellitus can no longer be perceived as an endocrine disorder only
      bearing high risk of microvascular complications. Further research involving
      prospective clinical trials will be necessary to clarify the benefits of early
      detection and treatment of diabetes in preventing the subsequent development or
      exacerbation of CVD.

PMID- 19574920
TI  - Refractive and topographic results of transepithelial cross-linking treatment in
      eyes with intacs.
AB  - PURPOSE: To evaluate the efficacy of transepithelial cross-linking (CXL) in
      keratoconic eyes after Intacs implantation. PATIENTS AND METHODS: Twenty-five
      eyes of 17 patients with bilateral keratoconus underwent Intacs implantation with
      subsequent cross-linking (CXL) treatment. Inclusion criteria were absence of
      corneal scarring, contact lens intolerance, corneal thickness higher than 400
      mum, and endothelial cell density more than 3000 per square millimeter.
      Preoperative and 3-month-postoperative uncorrected visual acuity (UCVA), best
      corrected visual acuity (BCVA), manifest refractions, and mean and steepest
      keratometric (K) values were reviewed retrospectively. The results in Intacs
      group were compared with those obtained after CXL/Intacs. RESULTS: There were 10
      males and 5 females; mean age was 25.14 +/- 7.11 (range 16-39) years old. Mean
      time between implantation of Intacs and CXL was 3.98 months. CXL after Intacs
      resulted in an additional improvement in UCVA, BCVA, sphere, cylinder, and
      keratometry. Intacs resulted in an improvement of 1.9 Snellen lines (P < 0.05) of
      UCVA and 1.7 Snellen lines (P < 0.05) of BCVA. CXL performed after Intacs
      treatment yielded an additional 1.2 Snellen lines (P < 0.05) of UCVA and 0.36
      Snellen lines (P < 0.05) of BCVA. The decrease in spherical, cylindrical, mean K,
      and steepest K values was 2.08 diopters (D) (P < 0.05), 0.47 D (P > 0.05), 2.22 D
      (P < 0.05), and 1.27 D (P < 0.05), respectively, after Intacs treatment with an
      additional 0.5 D (P < 0.05), 0.15 D (P > 0.05), 0.35 D (P > 0.05), and 0.76 D (P
      < 0.05) of improvement gained after CXL in each respective parameter.
      CONCLUSIONS: Intacs implantation with transepithelial CXL is effective in eyes
      with keratoconus. Collagen cross-linking has an additive effect on Intacs
      implantation in these eyes and may be considered as an enhancement/stabilizing
      procedure.

PMID- 19574922
TI  - Enhancing cardiovascular disease risk reduction: raising high-density lipoprotein
      levels.
AB  - PURPOSE OF REVIEW: Despite optimally reducing low-density lipoprotein cholesterol
      (LDL-C) levels to recommended targets using intensive statin therapy, the risk of
      cardiovascular disease (CVD) remains significant. Low levels of high-density
      lipoprotein cholesterol (HDL-C; <1.03 mmol/l or <40 mg/dl) are an independent
      risk factor for CVD, and raising levels of HDL-C is a major treatment strategy
      for regressing atherosclerosis and enhancing CVD risk reduction. This can be
      achieved by both nonpharmacological lifestyle measures and pharmacological
      treatment strategies. RECENT FINDINGS: This article will focus on the currently
      available and emerging pharmacological treatment strategies for raising HDL-C.
      Extended-release nicotinic acid (or Niacin) remains the most effective
      pharmacological treatment currently available for elevating HDL-C, having
      recently been combined with simvastatin (as Simcor) and laropripant (as
      Cordaptive, to reduce flushing). Other HDL-C-raising agents in current clinical
      use or in clinical development are fibrates, peroxisome proliferator-activated
      receptor agonists, cholesteryl ester transfer protein inhibitors, and HDL-C
      mimetics. Novel pharmacological targets for raising HDL-C also include the
      nuclear liver X and farnesoid X receptors and endothelial lipase. SUMMARY: Novel
      well tolerated and efficacious treatment strategies for raising HDL-C are
      required to target atherosclerosis and enhance CVD risk reduction.

PMID- 19574923
TI  - When statin therapy stops: implications for the patient.
AB  - PURPOSE OF REVIEW: To discuss recent findings on the implications of statin
      discontinuation. RECENT FINDINGS: The beneficial effects of statins in decreasing
      inflammatory markers, cardiovascular events, cardiovascular mortality, and all
      cause mortality in patients with and without a history of cardiovascular disease
      have been underscored in past and recent studies. However, patients often do not
      adhere to their statin therapy. Discontinuation rates, though improved over time,
      remain high not only in primary but also in secondary prevention patients in the
      clinical practice. Recent studies have found that discontinuing statins,
      particularly after acute events (e.g. acute myocardial infarction or stroke), has
      a harmful effect on cardiovascular outcomes and all-cause mortality; patients who
      discontinued their statin therapy had worse outcomes than those who were never
      prescribed statins. This could be attributed to a biological rebound phenomenon.
      SUMMARY: Statin therapy has a number of beneficial effects on patient outcomes
      and should be prescribed according to current cardiovascular disease guidelines.
      Importantly, statin discontinuation is associated with harmful outcomes.
      Clinicians should become more aware of these effects and counsel their patients
      to adhere to their statin therapy. Current evidence suggests that, unless
      contraindicated, statins should not be discontinued, especially after an acute
      vascular event.

PMID- 19574924
TI  - Cost-effectiveness of colorectal cancer screening with computed tomography
      colonography according to a polyp size threshold for polypectomy.
AB  - OBJECTIVE: Computed tomography colonography (CTC) has an acceptable accuracy in
      detecting colonic lesions, especially for polyps at least 6 mm. The aim of this
      analysis is to determine the cost-effectiveness of population-based screening for
      colorectal cancer (CRC) using CTC with a polyp size threshold. METHODS: The cost
      effectiveness ratios of CTC performed at 50, 60 and 70 years old, without (PL
      strategy) or with (TS strategy) polyp size threshold were compared using a Markov
      process. Incremental cost-effectiveness ratios (ICER) were calculated per life
      years gained (LYG) for a time horizon of 30 years. RESULTS: The ICER of PL and TS
      strategies were 12 042 and 2765 euro/LYG associated to CRC prevention rates of
      37.9 and 36.5%. The ICER of PL and TS strategies dropped to 9687 and 1857
      euro/LYG when advanced adenoma (AA) prevalence increased from 6.9 to 8.6% for
      male participants and 3.8-4.9% for female participants or to 9482 and 2067
      euro/LYG when adenoma and AA annual recurrence rates dropped to 3.2 and 0.25%.
      The ICER for PL and TS strategies decreased to 7947 and 954 euro/LYG or when only
      two CTC were performed at 50 and 60-years-old. Conversely, the ICER did not
      significantly change when varying population participation rate or accuracy of
      CTC. CONCLUSION: CTC with a 6 mm threshold for polypectomy is associated to a
      substantial cost reduction without significant loss of efficacy. Cost
      effectiveness depends more on the AA prevalence or transition rate to CRC than on
      CTC accuracy or screening compliance.

PMID- 19574925
TI  - The use of botulinum toxin for the treatment of muscle spasticity in the first 2
      years of life.
AB  - Although there are sound theoretical reasons for the use of botulinum toxin (Btx)
      as early as possible in the management of severe childhood muscle spasticity, the
      experience with its safety in children younger than 2 years of age is limited and
      information about its possible effects on the development and maturation of the
      human motor system is still scarce. This study discusses the rationale and the
      potential pitfalls of the use of Btx in the first 2 years of the child's life. It
      also reviews the currently available evidence on the efficacy and safety of Btx
      in this age group. It concludes by suggesting a framework for studies of the
      optimal time to start treatment of childhood spasticity with Btx.

PMID- 19574926
TI  - Abnormalities of erythropoiesis during HIV-1 disease: a longitudinal analysis.
AB  - BACKGROUND: Impaired erythropoiesis is a key abnormality described in untreated
      HIV-1 disease. Most of the available data on HIV-associated hematopoietic
      abnormalities were obtained using unfractionated bone marrow-derived mononuclear
      cells, thus resulting in significant inter (and intra)-individual variability in
      the number of cultured precursors. Aim of this study was to assess the
      erythropoietic capability of purified CD34+ progenitors through a longitudinal
      analysis of burst-forming units-erythroid (BFU-E) growth before and after
      antiretroviral therapy (ART). METHODS: Twelve HIV-infected individuals were
      studied before and after ART; 31 HIV-uninfected individuals were enrolled as
      controls. CD34+ progenitors were purified from peripheral blood by immunomagnetic
      sorting and cultured in methylcellulose-based medium containing stem cell factor,
      granulocyte-monocyte colony-stimulating factor, interleukin-3, and
      erythropoietin. Serum levels of iron, transferrin, transferrin saturation index,
      soluble transferrin receptor, ferritin, and erythropoietin were also evaluated.
      RESULTS: Baseline BFU-E levels were increased in untreated HIV-infected
      individuals when compared with controls but declined significantly after
      successful ART. In contrast, serum levels of erythropoietin and soluble
      transferrin receptor increased significantly after ART. CONCLUSIONS: These
      findings suggest that, in untreated HIV-infected individuals, chronic
      inflammation and/or immune activation is associated with defective erythropoiesis
      and accumulation of erythroid precursors. ART-induced suppression of HIV-1
      replication is associated with normalization of BFU-E levels.

PMID- 19574927
TI  - HIV testing outside of the study among men who have sex with men participating in
      an HIV vaccine efficacy trial.
AB  - OBJECTIVES: Participants who obtain an HIV test outside of an HIV vaccine
      efficacy trial could potentially unblind themselves which could result in
      differential behavior change and loss to follow-up based on assignment status. In
      a reanalysis of the VaxGen VAX004 data, the objectives were to determine: 1) the
      proportion of participants who were tested for HIV outside of the study (despite
      instructions not to do this) and reasons why; 2) demographic and risk factors
      associated with reported testing outside of the study; and 3) if outside testing
      was related to participant loss to follow-up. METHODS: Analyses were restricted
      to men who have sex with men (MSM) who completed a survey at one or more annual
      visits in a randomized, double-blind, placebo-controlled efficacy trial of a
      bivalent rgp 120 vaccine conducted from 1998-2002. A generalized linear mixture
      model assessed associations with outside testing. RESULTS: Despite instructions
      to the contrary, 16.9% (791/4670) of MSM reported being tested for HIV outside of
      the study, with the top two reasons being a) medical provider request (28.1%) and
      b) insurance requirement (17.1%). Increased odds of self-reported outside testing
      was associated with site location, reporting one or more sexually transmitted
      infections (STIs), joining the trial because of the belief that participation
      might confer some protection against HIV infection, engaging in unprotected anal
      sex, and being lost to follow-up. Decreased odds of self-reported outside testing
      was associated with perceived study arm assignment to vaccine or uncertainty
      about study arm assignment compared to placebo. CONCLUSIONS: To avoid biases such
      as differential risk behavior and loss to follow-up based on perceived assignment
      status, initiating additional procedures to reduce the likelihood of outside
      testing will be important to assure the validity of future study results.

PMID- 19574928
TI  - Mouse models of fragile X-associated tremor ataxia.
AB  - OBJECTIVE: To describe the development of mouse models of fragile X-associated
      tremor/ataxia (FXTAS) and the behavioral, histological and molecular
      characteristics of these mice. METHOD: This paper compares the pathophysiology
      and neuropsychological features of FXTAS in humans to the major mouse models of
      FXTAS. Specifically, the development of a transgenic mouse line carrying an
      expanded CGG trinucleotide repeat in the 5'-untranslated region (5'-UTR) of the
      Fmr1 gene is described along with a description of the characteristic
      intranuclear ubiquitin-positive inclusions and the behavioral sequella observed
      in these mice. RESULTS: CGG KI mice model many of the important features of
      FXTAS, although some aspects are not well modeled in mice. Aspects of FXTAS that
      are modeled well include elevated levels of Fmr1 mRNA, reduced levels of Fmrp,
      the presence of intranuclear inclusions that develop with age and show similar
      distributions within neurons, and neuropsychological and cognitive deficits,
      including poor motor function, impaired memory and evidence of increased anxiety.
      Features of FXTAS that are not well modeled in these mice include intentional
      tremors that are observed in some FXTAS patients but have not been reported in
      CGG KI mice. In addition, although intranuclear inclusions in astrocytes are very
      prominent in FXTAS, there are relatively few observed in CGG KI mice. A number of
      additional features of FXTAS have not been systematically examined in mouse
      models yet, including white matter disease, hyperintensities in T2-weighted
      magnetic resonance imaging, and brain atrophy, although these are currently under
      investigation in our laboratories. CONCLUSIONS: The available mouse model has
      provided valuable insights into the molecular biology and pathophysiology of
      FXTAS and will be particularly useful for developing and testing new therapeutic
      treatments in the future.

PMID- 19574930
TI  - Study of implementation of a guideline for brief alcohol intervention in primary
      care.
AB  - Application of research findings to clinical care has been advocated to improve
      quality of care and patient outcomes. This article discusses a method to evaluate
      the translation of research findings in support of evidence-based care. An
      exemplar of a brief intervention in primary care for high-risk drinkers is used.

PMID- 19574931
TI  - Work-arounds and artifacts during transition to a computer physician order entry:
      what they are and what they mean.
AB  - This study examined work-arounds and artifacts in the work performed by nurses
      and other healthcare providers when physicians transitioned to a computer
      physician order entry system. There were 5 types of work-arounds and artifacts
      identified: (1) workflow timing of events, (2) communication changes, (3) system
      problems, (4) learning curve, and (5) patient safety. Benefits of this study
      include the ability to understand how nursing work changes in the transition to a
      computer physician order entry system.

PMID- 19574929
TI  - Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and
      treatment.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative
      disorder caused by a CGG repeat expansion in the premutation range (55-200) in
      the fragile X mental retardation 1 gene. Onset is typically in the early seventh
      decade, and men are principally affected. The major signs are cerebellar gait
      ataxia, intention tremor, frontal executive dysfunction, and global brain
      atrophy. Other frequent findings are parkinsonism (mild), peripheral neuropathy,
      psychiatric symptoms (depression, anxiety, and agitation), and autonomic
      dysfunction. The clinical presentation is heterogeneous, with individuals
      presenting with varied dominating signs, such as tremor, dementia, or neuropathy.
      Magnetic resonance imaging shows atrophy and patchy white matter lesions in the
      cerebral hemispheres and middle cerebellar peduncles. The latter has been
      designated the middle cerebellar peduncle sign, which occurs in about 60% of
      affected men, and is relatively specific for FXTAS. Affected females generally
      have less severe disease, less cognitive decline, and some symptoms different
      from that of men, for example, muscle pain. Management of FXTAS is complex and
      includes assessment of the patient's neurological and medical deficits, treatment
      of symptoms, and provision of relevant referrals, especially genetic counseling.
      Treatment is empirical, based on anecdotal experience and on knowledge of what
      works for symptoms of other disorders that also exist in FXTAS. Presently, the
      disorder is underrecognized because the first published report was only in 2001
      and because the presentation is variable and mainly consists of a combination of
      signs common in the elderly. However, accurate diagnosis is critical for the
      patient and for the family because they need education regarding their genetic
      and health risks.

PMID- 19574932
TI  - IFCT-0401 Trial: a phase II study of gefitinib administered as first-line
      treatment in advanced adenocarcinoma with bronchioloalveolar carcinoma subtype.
AB  - PURPOSE: Intergroupe Francophone de Cancerologie Thoracique-0401 phase II trial
      aimed to evaluate the efficacy and safety of gefitinib as a first-line treatment
      for patients with adenocarcinoma with bronchioloalveolar carcinoma subtype (ADC
      BAC). METHODS: Chemotherapy-naive patients (n = 88) with advanced ADC-BAC were
      treated with 250 mg/d of gefitinib. The primary objective was assessment of
      disease control rate (DCR [objective response + stable disease]) at 3 months
      using World Health Organization criteria. A disease control rate of 25% or
      greater would be of interest in this patient population. Progression-free
      survival (PFS), overall survival (OS), and toxicity were the secondary criteria.
      Clinical and disease characteristics that conferred a favorable prognosis under
      gefitinib were also analyzed. RESULTS: Disease control was achieved in 25
      patients (29.4%); 11 patients (12.9%) had partial response and 14 (16.4%) had
      stable disease. Median PFS was 2.9 months (95% confidence interval [CI], 2.3-3.2)
      and median OS was 13.2 months (95% CI, 10.2-17.3). Never smokers, patients with
      low respiratory symptoms score, occurrence of cutaneous rash, and nonmucinous ADC
      BAC subtype were associated with increased probability of disease control.
      Nonmucinous ADC-BAC was associated with increased PFS and OS at 3 years. Patients
      with nonmucinous BAC had longer OS and PFS compared with patients with other ADC
      BAC variants; median PFS for nonmucinous BAC was 11.3 months (95% CI, 3.2-14.7),
      whereas it was 2.6 months (95% CI, 2.1-3) for mucinous BAC. As expected, toxicity
      was low, with dermatological problems, diarrhea, and nausea being the most common
      adverse events. CONCLUSION: Results from the Intergroupe Francophone de
      Cancerologie Thoracique-0401 trial demonstrate that gefitinib combines efficacy
      with low toxicity and is, therefore, suitable as a first-line treatment of
      advanced ADC-BAC, particularly in patients with nonmucinous BAC subtype.

PMID- 19574933
TI  - Coexpression of major histocompatibility complex class II with chemokines and
      nuclear NFkappaB p50 in melanoma: a rational for their association with poor
      prognosis.
AB  - The constitutive expression of major histocompatibility complex class II (MHC II)
      molecules in melanoma is highly unusual and has been associated with unfavorable
      clinical outcome and higher metastatic dissemination. This association remains
      poorly understood and therefore, in this study we looked to whether it is caused
      by intracellular events that promote tumor progression. We previously reported
      that MHC II expression in melanoma cells requires active mitogen-activated
      protein kinase/extracellular signal-related kinase. However, our comparative and
      molecular analyses of a panel of melanoma cell lines herein provide clear
      evidence that mitogen-activated protein kinase/extracellular signal-related
      kinase is not sufficient for HLA-DR expression. We found that the expression of
      HLA-DR in these tumors rather coincides with the expression of CXCL-1 and CXCL-8
      chemokines, both known to be expressed in tumors that invade early and are
      related to invasive stages of melanoma. The expression of HLA-DR also nicely
      paralleled that of the nuclear NFkappaB p50 subunit, regulating the expression of
      these chemokines in melanoma and previously correlated with poor prognosis of
      melanoma patients, although we provide evidence that NFkappaB is not directly
      regulating MHC II expression level. The molecular basis for class II
      transactivator and HLA-DR expression in melanoma therefore remains unsolved, but
      our findings linking together the expression of HLA-DR, of chemokines involved in
      invasiveness, and of nuclear NFkappaB p50 strongly support the content that MHC
      II may be a marker of invasive primary melanoma, and could explain the long
      standing association of MHC II expression with overall poor prognosis and
      unfavorable clinical outcome.

PMID- 19574934
TI  - Menopause and physical fitness.

PMID- 19574935
TI  - Transvaginal dehydroepiandrosterone: an unconventional proposal to deliver a
      mysterious androgen that has no receptor or target tissue using a strategy with a
      new name: hormone precursor replacement therapy (HPRT).

PMID- 19574936
TI  - Vaginal symptoms in postmenopausal women: self-reported severity, natural
      history, and risk factors.
AB  - OBJECTIVE: This study aimed to examine factors other than estrogen deficiency
      influencing the development and persistence of vaginal dryness, itching, and
      painful sexual intercourse after menopause. METHODS: We analyzed data from a 2
      year, population-based cohort of 1,017 postmenopausal women aged 55 to 75 years.
      Vaginal symptoms were assessed by interviewer-administered questionnaire, and
      vaginal swabs were performed to assess vaginal pH and microbial flora at
      baseline, 12 months, and 24 months. Generalized estimating equations were used to
      identify characteristics associated with symptoms. RESULTS: Half of the women (n
      = 471) reported problematic vaginal dryness, a third (n = 316) reported itching,
      and 40% of sexually active women (n = 166) reported painful intercourse at
      baseline. Of women not taking estrogen, half of those reporting baseline symptoms
      were symptomatic after 24 months. Vaginal dryness was associated with younger age
      (odds ratio [OR], 0.81; 95% CI, 0.69-0.94, per 5-y increase), nonwhite race (ie,
      African American, Hispanic, Asian or Pacific Islander, or American Indian [OR,
      1.53; 95% CI, 1.04-2.27]), diabetes (OR, 1.51; 95% CI, 1.07-2.12), lower 36-item
      Short-Form Health Survey physical functioning scores (OR, 0.90; 95% CI, 0.85
      0.97, per 10-point increase), lower body mass index (OR, 0.81; 95% CI, 0.71-0.93,
      per 5 kg/m increase), recent sexual activity (OR, 1.14; 95% CI, 1.08-1.21), and
      vaginal colonization with enterococci (OR, 1.25; 95% CI, 1.04-1.51). Vaginal
      itching was also associated with lower physical functioning scores (OR, 0.86; 95%
      CI, 0.80-0.92, per 10-point increase). Risk factors for painful intercourse
      included younger age (OR, 0.72; 95% CI, 0.56-0.93, per 5-y increase), diabetes
      (OR, 3.48; 95% CI, 1.93-6.27), lower body mass index (OR, 0.76; 95% CI, 0.61
      0.95, per 5 kg/m increase), and higher vaginal pH (OR, 1.10; 95% CI, 1.00-1.21,
      per 0.5 units). CONCLUSIONS: Vaginal symptoms affect a large proportion of
      postmenopausal women, particularly those with diabetes and those with lower body
      mass index, but may resolve for up to half of women without estrogen therapy.

PMID- 19574937
TI  - Effects of alendronate treatment on serum levels of osteoprotegerin and total
      receptor activator of nuclear factor kappaB in women with postmenopausal
      osteoporosis.
AB  - OBJECTIVE: Bisphosphonates are potent inhibitors of bone resorption that are used
      as effective therapeutic agents for the management of osteoporosis and other bone
      diseases. The osteoprotegerin (OPG)-receptor activator of nuclear factor kappaB
      (RANKL) system plays an important role in the regulation of bone metabolism and
      vascular biology. The effects of bisphosphonate treatment in OPG-RANKL system
      have not been fully elucidated. The aims of the study were to evaluate the
      effects of alendronate treatment (70 mg once/wk) on serum concentrations of OPG,
      total RANKL, and biochemical markers of bone turnover in untreated women with
      postmenopausal osteoporosis and to determine the correlation between changes in
      bone mineral density and changes in serum OPG, total RANKL, and bone turnover
      markers. METHODS: The study was a single group pretest/posttest design including
      a total number of 46 participants. Serum OPG and total RANKL serum levels were
      determined before and after 3, 6, and 12 months of treatment with alendronate. We
      also measured serum carboxyterminal cross-linked telopeptide of type I collagen,
      osteocalcin, and bone-specific alkaline phosphatase. The main outcome measures
      are the changes in OPG and total RANKL serum levels after alendronate treatment.
      RESULTS: Serum OPG changes were not significant at 3 and 6 months (-1.6% and 
      1%), but at 12 months, there was a significant reduction of 6.5% (P < 0.01).
      Total RANKL serum levels increased during treatment: 23% at 3 months, 25% at 6
      months, and 52% at 12 months (P < 0.001 for all comparisons). Basal levels of
      OPG, total RANKL, and bone turnover markers were not correlated, and we did not
      find correlations between changes in these parameters after treatment.
      CONCLUSIONS: We conclude that the determination of total RANKL integrates the
      free RANKL and the fraction bound to OPG. The apparent decrease in the serum
      levels of OPG might reflect an increase in OPG binding to RANKL, which results in
      a beneficial effect on bone.

PMID- 19574938
TI  - Ovarian status in healthy postmenopausal women: follow-up 12 months after
      transvaginal ultrasound.
AB  - OBJECTIVE: We have previously reported on the point prevalence of ovarian lesions
      detected by transvaginal ultrasound (TVU) in 515 asymptomatic women at least 5
      years postmenopause. The aims of this study were to report, in the same women, on
      the repeatability of visualization of the ovaries (TVU) and the natural history
      of ovarian lesions seen at baseline but not treated surgically and to assess
      whether any women developed new ovarian abnormalities 12 months later. METHODS:
      The study involved a cohort of 515 postmenopausal women recruited from the
      community, at least 5 years past their last period. They were assessed at
      baseline and again after 12 months with TVU and serum levels of inhibin and CA
      125. RESULTS: The right and left ovaries were seen on both occasions in 80% and
      68% of women, respectively. Of the 49 women who had an ovarian lesion at
      baseline, did not undergo surgery at that time, and had a follow-up TVU, the
      lesion was unchanged 12 months later in 30 women. Four women developed a new
      ovarian lesion within the 12 months. None of the 14 women who underwent surgery
      on the basis of the ovarian appearance at baseline, or the 2 who had surgery on
      the basis of the ovarian appearance at follow-up, had an ovarian malignancy.
      CONCLUSIONS: The use of TVU in women at least 5 years after menopause is
      problematic because the ovaries cannot be visualized in all women and because TVU
      has the potential to identify many benign lesions that would otherwise remain
      undetected. These are important considerations in weighing up the risks and
      benefits of using TVU as a screening tool.

PMID- 19574939
TI  - Effect of variation in relaxation parameter value on LOR-RAMLA reconstruction of
      18F-FDG PET studies.
AB  - PURPOSE: We tested the impact of different values of the relaxation parameter
      lambda (lambda) on contrast and noise in line-of-response row-action maximum
      likelihood algorithm (LOR-RAMLA) in 18F-fluorodeoxyglucose positron emission
      tomography (PET)/computed tomography (CT) imaging. METHODS: Phantom studies were
      performed on a Gemini XL PET/CT scanner. The NEMA/IEC (National Electrical
      Manufacturers Association/International Electro technical Commission) torso
      phantom was used and acquisition data were reconstructed with lambda values
      ranging from 0.025 to 0.1. Quality of the reconstructed images was evaluated by
      contrast recovery coefficients and background variability values according to the
      NEMA NU 2-2001 procedures. RESULTS: Contrast recovery coefficients and background
      variability increased significantly when lambda increased. The best noise-versus
      resolution trade-off was obtained with lambda in the 0.04-0.06 range. For LOR
      RAMLA reconstruction, the manufacturer allows a possible lambda choice from 0.025
      to 0.1. We would not advise too small (0.025) or too large (0.1) lambda values
      which result in too smooth or too noisy images. CONCLUSION: We determined optimal
      lambda values in LOR-RAMLA on a Gemini XL PET/CT scanner. Caution is needed when
      using lambda values out of that range.

PMID- 19574940
TI  - Optimization of the parameters of a method for computer-aided detection of
      perfusion deficiencies in brain images.
AB  - OBJECTIVE: Simulated data from the recent Institute of Physics and Engineering in
      Medicine audit of quantitative cerebral perfusion were used to optimize the
      parameters of eigenimage analysis, a method for computer-aided detection.
      METHODS: Twenty normal images provided by the audit were registered to the
      International Consortium for Brain Mapping 452 template using HERMES
      multimodality software and normalized to total counts. Six normal atlases were
      formed using the mean image and from zero to five eigenimages. Eight patient
      images, with computer-simulated lesions at known positions, were similarly
      registered and normalized. For each atlas, z-score images were formed for each
      patient. Thresholds of z0 = 2-5 in intervals of 0.5 were applied to the z-score
      images to form binary images of normal and abnormal voxels. A lesion was defined
      as a connected group of abnormal voxels with a minimum size of 1 ml. Lesions were
      assigned to one of 12 regions defined by the template. For eight patients, this
      gave 96 regions, 19 of which were known to contain an abnormality. Receiver
      operating characteristic analysis was performed for the regions using z0 as a
      variable threshold. RESULTS: For the receiver-operating characteristic analysis,
      an optimal area under the curve of approximately 0.90 was found using either one
      or three eigenimages, whereas good results (sensitivity = 0.75%; specificity =
      90%) were obtained for a threshold of z0 approximately equal to 3. When the
      number of images in the normal dataset was considered, a meta-analysis showed
      consistency with other studies. CONCLUSION: Eigenimage analysis was shown to give
      good diagnostic accuracy for cerebral perfusion images based on objective
      evaluation using simulated images.

PMID- 19574941
TI  - Improve clinical outcomes for cochlear implant recipients by mimicing the viable
      cochlear environment to induce neural stem cells to differentiate into auditory
      neurons.

PMID- 19574942
TI  - Treatment of otogenic brain abscess in pregnancy.
AB  - OBJECTIVE: Otogenic intracranial abscess complicating pregnancy has not been
      reported in world literature. We report the first case of cerebellar abscess
      secondary to chronic suppurative otitis media (CSOM) in a 23-year-old lady at 35
      weeks of gestation. She was successfully treated by Caesarean section and
      delivery of a healthy baby, followed by combined neurosurgical and otologic
      procedures in the same anesthetic sitting. STUDY DESIGN: Case report. SETTING:
      Tertiary care referral center in a developing country. CONCLUSION: Otogenic
      intracranial abscess complicating pregnancy is an extremely challenging
      therapeutic dilemma for the attending health care provider. Concurrent surgical
      management by multidisciplinary intervention is safe and to be considered the
      treatment of choice in a tertiary referral center.

PMID- 19574943
TI  - Superior vestibular neurectomy: a novel transmeatal approach for a denervation of
      the superior and lateral semicircular canals.
AB  - OBJECTIVE: To assess morphologically a transmeatal approach to the lateral and
      superior ampullary nerves performable under local anesthesia and simultaneously
      with the existing approach to the singular nerve developed by Gacek during the
      same operation. MATERIALS AND METHODS: Eighty halves of human heads preserved
      with the Thiel method were operated on by an otologist. Two surgical approaches
      were tested on each specimen, 1 superior and 1 inferior to the tympanic segment
      of the facial nerve. The 80 specimens were divided into 2 groups. In the first
      group, the osseous canal of the nerves of the lateral and superior semicircular
      canal were previously probed and next operated. In the second group, the osseous
      canal of the nerves were operated prior assessment by dissection. Afterward, all
      80 halves underwent computed tomographic investigation to measure the distance
      between the entrance point of the drill in the medial wall of the tympanic cavity
      and the osseous canal the ampullary nerves. RESULTS: Inferior approach to the
      canal of the nerves could not be done without wide opening of the vestibulum in
      all 80 specimens. In the superior approach, the nerve could be reached directly
      in 5 cases, and only via the osseous ampulla of the lateral semicircular canal in
      28 cases in the first group. In 7 cases, the nerves could not be reached without
      damage to the membranous labyrinth. In the second group, the nerve could be
      reached directly in 2 cases, via the osseous ampulla in 36 cases, and was
      unreachable in 2 cases. Significantly, distances longer than 3 mm between the
      surgical access and the nerve were found on the inaccessible cases. CONCLUSION: A
      transmeatal approach is possible superiorly but not inferiorly to the facial
      nerve, although it is necessary to open the osseous ampulla but not the
      membranous labyrinth in most cases.

PMID- 19574944
TI  - Recovery of facial movement and facial synkinesis in Bell's palsy patients.
AB  - OBJECTIVE: We examined the relationship between the time course of development of
      facial synkinesis in patients with Bell's palsy and the severity of facial nerve
      damage. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center.
      PATIENTS: Thirty-nine consecutive patients with Bell's palsy who developed
      synkinesis. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Subjects were
      divided into groups A (electroneurographic [ENoG] value, <10%; n = 31) and B
      (ENoG value, > or =10%; n = 8). Development of facial synkinesis was assessed
      based on the appearance of synkinetic potentials from the orbicularis oris muscle
      on the blink reflex test. Times to appearance of facial synkinesis in groups A
      and B were compared. The proportion of patients who developed facial synkinesis
      after complete recovery of facial movement was also assessed in 14 patients whose
      facial movement recovered completely. RESULTS: The mean time to maximal recovery
      of facial movement was significantly longer in group A than in group B (p <
      0.001), whereas the duration between the appearance of facial synkinesis and the
      onset of facial paralysis did not differ significantly between the 2 groups (p =
      0.72). The proportion of patients who developed facial synkinesis after complete
      recovery of facial movement was significantly greater in group B than in group A
      (p = 0.015). CONCLUSION: During the course of recovery from Bell's palsy, the
      patients with an ENoG value of 10% or greater have a higher risk of developing
      facial synkinesis after complete recovery of facial movement.

PMID- 19574945
TI  - Cochlear third window in the scala vestibuli: an animal model.
AB  - BACKGROUND: Pathologic third window has been investigated in both animals and
      humans, with a third window located in the vestibular apparatus, specifically,
      dehiscence of the superior semicircular canal, serving as the clinical model.
      HYPOTHESIS: The present study sought to examine the effect of a cochlear third
      window in the scala vestibuli on the auditory thresholds in fat sand rats that
      have a unique anatomy of the inner ear that allows for easy surgical access.
      METHODS: The experiment included 7 healthy 6-month-old fat sand rats (a total of
      10 ears). A pathologic third window was induced by drilling a hole in the bony
      labyrinth over the scala vestibuli, with preservation of the membranous
      labyrinth. Auditory brainstem responses to high- and low-frequency acoustic
      stimuli delivered via air and bone conduction were recorded before and after the
      procedure. RESULTS: In the preoperative auditory brainstem response recordings,
      air-conduction thresholds (ACTs) to clicks and tone bursts averaged 9 and 10 dB,
      respectively, and bone-conduction thresholds averaged 4.5 and 2.9 dB,
      respectively. Postfenestration ACTs averaged 41 and 42.2 dB, and bone-conduction
      thresholds averaged 1.1 and 4.3 dB. The change in ACT was statistically
      significant (p < 0.01). CONCLUSION: The presence of a cochlear third window in
      the scala vestibuli affects auditory thresholds by causing a decrease in
      sensitivity to air-conducted sound stimuli. These findings agree with the
      theoretical model and clinical findings.

PMID- 19574946
TI  - Early static pressure-related evoked brain potentials indications of central
      middle ear pressure control in humans.
AB  - HYPOTHESIS: The aim of this study was to investigate the possibility of afferent
      subcortical components related to static pressure changes of the human middle
      ear. BACKGROUND: The normal middle ear function depends on a proper regulation of
      middle ear pressure, whereas an inadequate regulation with negative pressures is
      considered a major pathogenetic factor responsible for a variety of middle ear
      disorders. However, although studies on middle ear pressure and related clinical
      problems are common, studies on the role of its central control have been
      remarkably few. Hence, we attempted recording evoked brain potentials in response
      to static pressure stimulation of the middle ear in normal adult humans. METHODS:
      The experiments were conducted by stimulating the middle ear in 6 subjects with a
      novel computer-controlled static pressure triggering system for rapid
      synchronized pressure loads of +3 kPa. The resulting brain evoked responses were
      recorded from 64 surface electrodes using a standard electroencephalogram cap. A
      wide-band electroencephalogram acquisition method was adopted, signals were
      sampled at 20,000 Hz, and band-pass filtered between 150 and 3,000 Hz. RESULTS:
      Repeatable pressure evoked brain potentials and topographies were described for
      the first time. Hence, source localization could be adopted on a realistic head
      model, which showed the location of these early neural generators in the
      brainstem, followed by activity generated by the cerebellum. CONCLUSION: The
      findings are in agreement with previous animal experiments and provide basic
      information for further investigations on central components related to static
      pressure changes of the human middle ear.

PMID- 19574947
TI  - Tinnitus treatment with piribedil guided by electrocochleography and acoustic
      otoemissions.
AB  - INTRODUCTION: Tinnitus is a frequent disorder and very difficult to treat. Both
      animal studies and clinical observations suggest that dopaminergic substances
      might have potential for the treatment of tinnitus. Here, we investigated the
      dopamine agonist piribedil for the treatment of chronic tinnitus. In all
      participants, we performed audiometry, electrocochleography (ECoG), and
      otoacoustic emissions before treatment began. OBJECTIVE: To assess the efficacy
      and safety of the dopaminergic drug piribedil for the treatment of tinnitus and
      to evaluate whether ECoG and acoustic otoemissions might be useful for predicting
      treatment response. STUDY DESIGN: Prospective randomized double-blind crossover
      study. SUBJECTS AND METHOD: One hundred patients with tinnitus were randomized
      into a double-blind, placebo-controlled, prospective crossover study. All
      patients underwent distortion product acoustic otoemissions with and without
      contralateral suppression and ECoG. Patients received 50 mg piribedil and placebo
      for 90 days each, separated by a 30-day washout period. Treatment effects were
      assessed by using the Tinnitus Handicap Inventory and a visual analog scale.
      Fifty-six patients completed the trial. RESULTS: There was no significant
      improvement of Tinnitus Handicap Inventory and visual analog scale score after
      piribedil treatment as compared with placebo. However, results were characterized
      by high interindividual variability. Post hoc analysis of piribedil effects
      revealed that piribedil treatment responders differed from nonresponders by the
      occurrence of a double peak in the ECoG. In addition, normal distortion product
      acoustic otoemission suppression patterns indicated better treatment response
      with piribedil. The incidence of side effects during piribedil treatment was
      23.3%, leading to interruption of treatment in all cases. CONCLUSION: Piribedil
      is not superior to placebo in the treatment of tinnitus. Piribedil treatment
      responders differed from nonresponders by specific findings in the ECoG and in
      the distortion product acoustic otoacoustic emissions, suggesting a beneficial
      effect of piribedil in an electrophysiologically characterized tinnitus subgroup.

PMID- 19574948
TI  - Stimulation of the facial nerve by intracochlear electrodes in otosclerosis: a
      computer modeling study.
AB  - HYPOTHESIS: The increased likelihood of facial nerve stimulation (FNS) with
      cochlear implantation in advanced cochlear otosclerosis is due to a lowering of
      the facial nerve excitation threshold with increasing bone demineralization.
      BACKGROUND: Facial nerve stimulation can complicate cochlear implant fitting,
      often necessitating the deactivation of certain electrode contacts. METHODS: High
      resolution computed tomographic scans were used to estimate anatomic features of
      the cochlea and the facial nerve canal. These features were added to a detailed
      computational model of the implanted human cochlea to examine the consequences of
      increased conductivity of the bone of the otic capsule. The model took into
      account the electrode contact type (banded or otherwise) and position
      (perimodiolar or lateral wall) of the electrode array. RESULTS: Contrary to the
      hypothesis, facial nerve thresholds were found to be slightly elevated with
      increased conductivity of the surrounding bone. However, the threshold and most
      comfortable loudness levels of the auditory nerve increase more rapidly owing to
      the reduced current density in the scala tympani as current leaks more easily out
      of the cochlea. Lateral wall electrodes were predicted to result in an increased
      likelihood of FNS. A progressively reduced probability of FNS was indicated for
      the full-band, half-band, and plated electrode arrays, respectively. CONCLUSION:
      The clinical observation of increased FNS in cases of cochlear otosclerosis has
      been demonstrated in a computational model. Rather than decreased FN threshold,
      it is the increased levels for cochlear stimulation that is the main factor.
      Particularly, perimodiolar designs with more shielding against lateral spread of
      current could reduce the likelihood of FNS.

PMID- 19574949
TI  - Aggressive posterior retinopathy of prematurity in Asian Indian babies: spectrum
      of disease and outcome after laser treatment.
AB  - PURPOSE: To analyze the spectrum of aggressive posterior retinopathy of
      prematurity and outcome after laser treatment. METHODS: This is a retrospective
      review of 81 eyes of 44 consecutive infants diagnosed to have aggressive
      posterior retinopathy of prematurity and treated between September 2005 and March
      2007 from a large tertiary care center in North India. Qualitative variables were
      tested for statistical significance using the chi-square test and independent
      samples with the student's t-test. RESULTS: Mean birth weight and gestational age
      were 1,259.66 +/- 310.51 g (range, 660-2,000 g) and 29.75 +/- 2.35 weeks (range,
      26-36 weeks), respectively. Twenty-one infants (47.72%) had a birth weight >
      1,250 g. Thirty-three (40.74%) eyes had Zone 1, and 48 (59.26%) had posterior
      Zone 2 disease. All eyes underwent confluent laser photocoagulation at a mean
      postconceptional age of 34.58 +/- 2.19 weeks (range, 31-40.5 weeks). Mean follow
      up was 12.8 months (range, 6-24 months). At the last follow-up visit, 55 (71.4%)
      of 77 eyes had a favorable outcome. Eighteen eyes (23.4%) had a localized (1-3
      clock hours) partial peripheral tractional detachment (Stage 4a), which remained
      stable at last follow-up. Two eyes (2.6%) developed falciform fold involving the
      macular area, and 2 (2.6%) developed Stage 5 retinopathy of prematurity.
      CONCLUSION: Aggressive posterior retinopathy of prematurity is encountered not
      only in low birth weight infants, but also in heavier and more mature Asian
      Indian infants. Early, aggressive confluent laser photocoagulation is necessary
      to maximize outcomes in these eyes.

PMID- 19574951
TI  - Hepatitis a vaccination coverage among children aged 24-35 months - United
      States, 2006 and 2007.
AB  - During 1995-1996, hepatitis A vaccines were licensed in the United States as 2
      dose regimens for children aged >or=24 months. In 1996, the Advisory Committee on
      Immunization Practices (ACIP) recommended vaccinating children aged >or=24 months
      who lived in communities or states with high rates of hepatitis A. In 1999, ACIP
      updated its guidelines, recommending routine vaccination for children aged >or=24
      months in areas with hepatitis A rates twice the national average, and
      recommending consideration of routine vaccination in areas with rates higher than
      the national average. However, in 2005, this regional vaccination strategy was
      reevaluated because national hepatitis A rates had decreased to such an extent
      that differences among states were no longer substantial. Additionally, in 2005,
      hepatitis A vaccine was licensed for children aged 12-23 months. As a result of
      these developments, in 2006, ACIP expanded its hepatitis A vaccination
      recommendation to all children in the United States and reduced the recommended
      age for vaccination to 12-23 months. This report updates previous findings
      regarding hepatitis A vaccination coverage, providing estimates based on National
      Immunization Survey (NIS) data for 2006 and 2007. From 2006 to 2007, estimated
      national hepatitis A vaccination coverage levels among children aged 24-35 months
      who received at least 1 dose increased from 26.3% to 47.4%. The increase in
      hepatitis A vaccination coverage likely is the result of the expanded 2006 ACIP
      recommendations; adherence to these recommendations should lead to further
      declines in hepatitis A incidence in the United States.

PMID- 19574950
TI  - Ocular wavefront aberrations in patients with macular diseases.
AB  - BACKGROUND: There have been reports that by compensating for ocular aberrations
      using adaptive optical systems it may be possible to improve the resolution of
      clinical retinal imaging systems beyond what is now possible. To develop such a
      system to observe eyes with retinal disease, understanding of ocular wavefront
      aberrations in individuals with retinal disease is required. METHODS: Eighty-two
      eyes of 66 patients with macular disease (epiretinal membrane, macular edema,
      macular hole, etc.) and 85 eyes of 51 patients without retinal disease were
      studied. Using a ray-tracing wavefront device, each eye was scanned at both small
      and large pupil apertures, and Zernike coefficients up to the sixth order were
      acquired. RESULTS: In phakic eyes, third-order root mean square errors in the
      macular disease group were statistically greater than in the control group, an
      average of 12% for 5-mm and 31% for 3-mm scan diameters (P < 0.021). In
      pseudophakic eyes, there was also an elevation of third-order root mean square,
      on average 57% for 5-mm and 51% for 3-mm scan diameters (P < 0.031). CONCLUSION:
      Higher-order wavefront aberrations in eyes with macular disease were greater than
      in control eyes without disease. This study suggests that such aberrations may
      result from irregular or multiple reflecting retinal surfaces. Modifications in
      wavefront sensor technology will be needed to accurately determine wavefront
      aberration and allow correction using adaptive optics in eyes with macular
      irregularities.

PMID- 19574952
TI  - Recurring norovirus outbreaks in a long-term residential treatment facility -
      Oregon, 2007.
AB  - On November 9, 2007, the Oregon Public Health Division (OPHD) was notified of an
      outbreak of acute gastroenteritis in a long-term residential treatment facility.
      Two previous outbreaks caused by norovirus had occurred at the facility in March
      and July 2007. OPHD initiated an in-depth epidemiologic investigation, which
      included submitting archived and recent specimens from the three outbreaks to CDC
      for genotyping. This report summarizes findings of the outbreak investigation and
      laboratory testing. The overall attack rate for the most recent outbreak was
      approximately 14% among patients and 7% among employees. The outbreak was unusual
      in that it lasted 63 days, versus 24-27 days for the two previous outbreaks in
      2007. Person-to-person transmission was suggested by a prolonged and dispersed
      epidemic curve and lack of illness in some wards, although all wards were served
      by one central kitchen. Barriers to conducting adequate hygiene (e.g., lack of
      handwashing stations) and multiple lapses in infection control (e.g.,
      noncompliance with staff wellness policies) were identified. Timely and sustained
      implementation of comprehensive and effective infection control measures are
      needed to prevent and contain norovirus outbreaks in large institutional
      settings.

PMID- 19574953
TI  - Standardized preparation of single-cell suspensions from mouse lung tissue using
      the gentleMACS Dissociator.
AB  - The preparation of single-cell suspensions from tissues is an important
      prerequisite for many experiments in cellular research. The process of
      dissociating whole organs requires specific parameters in order to obtain a high
      number of viable cells in a reproducible manner. The gentleMACS Dissociator
      optimizes this task with a simple, practical protocol. The instrument contains
      pre-programmed settings that are optimized for the efficient but gentle
      dissociation of a variety of tissue types, including mouse lungs. In this
      publication the use of the gentleMACS Dissociator on lung tissue derived from
      mice is demonstrated.

PMID- 19574955
TI  - Concerted action of two cation filters in the aquaporin water channel.
AB  - Aquaporin (AQP) facilitated water transport is common to virtually all cell
      membranes and is marked by almost perfect specificity and high flux rates.
      Simultaneously, protons and cations are strictly excluded to maintain ionic
      transmembrane gradients. Yet, the AQP cation filters have not been identified
      experimentally. We report that three point mutations turned the water-specific
      AQP1 into a proton/alkali cation channel with reduced water permeability and the
      permeability sequence: H(+) >>K(+) >Rb(+) >Na(+) >Cs(+) >Li(+). Contrary to
      theoretical models, we found that electrostatic repulsion at the central asn-pro
      ala (NPA) region does not suffice to exclude protons. Full proton exclusion is
      reached only in conjunction with the aromatic/arginine (ar/R) constriction at the
      pore mouth. In contrast, alkali cations are blocked by the NPA region but leak
      through the ar/R constriction. Expression of alkali-leaking AQPs depolarized
      membrane potentials and compromised cell survival. Our results hint at the alkali
      tight but solute-unselective NPA region as a feature of primordial channels and
      the proton-tight and solute-selective ar/R constriction variants as later
      adaptations within the AQP superfamily.

PMID- 19574954
TI  - Insights into complement convertase formation based on the structure of the
      factor B-cobra venom factor complex.
AB  - Immune protection by the complement system critically depends on assembly of C3
      convertases on the surface of pathogens and altered host cells. These short-lived
      protease complexes are formed through pro-convertases, which for the alternative
      pathway consist of the complement component C3b and the pro-enzyme factor B (FB).
      Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray
      scattering and electron microscopy (EM) data of the pro-convertase formed by
      human FB and cobra venom factor (CVF), a potent homologue of C3b that generates
      more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment
      by specific contacts, which explain the specificity for the homologous C3b over
      the native C3 and inactive products iC3b and C3c. The protease segment Bb binds
      the carboxy terminus of CVF through the metal-ion dependent adhesion site of the
      Von Willebrand factor A-type domain. A possible dynamic equilibrium between a
      'loading' and 'activation' state of the pro-convertase may explain the observed
      difference between the crystal structure of CVFB and the EM structure of C3bB.
      These insights into formation of convertases provide a basis for further
      development of complement therapeutics.

PMID- 19574956
TI  - Increased RNA polymerase availability directs resources towards growth at the
      expense of maintenance.
AB  - Nutritionally induced changes in RNA polymerase availability have been
      hypothesized to be an evolutionary primeval mechanism for regulation of gene
      expression and several contrasting models have been proposed to explain how such
      'passive' regulation might occur. We demonstrate here that ectopically elevating
      Escherichia coli RNA polymerase (Esigma(70)) levels causes an increased
      expression and promoter occupancy of ribosomal genes at the expense of stress
      defense genes and amino acid biosynthetic operons. Phenotypically, cells
      overproducing Esigma(70) favours growth and reproduction at the expense of
      motility and damage protection; a response reminiscent of cells with no or
      diminished levels of the alarmone guanosine tetraphosphate (ppGpp). Consistently,
      we show that cells lacking ppGpp displayed markedly elevated levels of free
      Esigma(70) compared with wild-type cells and that the repression of ribosomal RNA
      expression and reduced growth rate of mutants with constitutively elevated levels
      of ppGpp can be suppressed by overproducing Esigma(70). We conclude that ppGpp
      modulates the levels of free Esigma(70) and that this is an integral part of the
      alarmone's means of regulating a trade-off between growth and maintenance.

PMID- 19574957
TI  - Mechanisms of regulation of RNA polymerase III-dependent transcription by TORC1.
AB  - We have found earlier that Tor1 binds to 5S rDNA chromatin but the functional
      significance has not been established. Here, we show that association with 5S
      rDNA chromatin is necessary for TOR complex 1 (TORC1) to regulate the synthesis
      of 5S ribosomal RNA and transfer RNAs (tRNAs) by RNA polymerase (Pol) III, as
      well as the phosphorylation and binding to Pol III-transcribed genes of the Pol
      III repressor Maf1. Interestingly, TORC1 does not bind to tRNA genes, suggesting
      that TORC1 modulates tRNA synthesis indirectly through Maf1 phosphorylation at
      the rDNA loci. We also find that Maf1 cytoplasmic localization is dependent on
      the SSD1-v allele. In W303 cells that carry the SSD1-d allele, Maf1 is
      constitutively nuclear but its nucleolar localization is inhibited by TORC1,
      indicating that TORC1 regulates nucleoplasm-to-nucleolus transport of Maf1.
      Finally, we show that TORC1 interacts with Maf1 in vivo and phosphorylates Maf1
      in vitro, and regulates Maf1 nucleoplasm-to-nucleolus translocation. Together,
      these observations provide new insights into the chromatin-dependent mechanism by
      which TORC1 controls transcription by Pol III.

PMID- 19574959
TI  - Novel genetic variants in the alpha-adducin and guanine nucleotide binding
      protein beta-polypeptide 3 genes and salt sensitivity of blood pressure.
AB  - BACKGROUND: We examined the association between 12 single-nucleotide
      polymorphisms (SNPs) in the alpha-adducin (ADD1) and guanine nucleotide binding
      protein (G protein) beta-polypeptide 3 (GNB3) genes and systolic (SBP), diastolic
      (DBP), and mean arterial (MAP) pressure responses to salt intake. METHODS: A 7
      day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium
      intervention (307.8 mmol sodium/day) was conducted among 1,906 Han participants
      from rural North China. Blood pressure (BP) measurements were obtained at
      baseline and at the end of each intervention period using a random-zero
      sphygmomanometer. RESULTS: We identified a significant association between a rare
      ADD1 variant rs17833172 and SBP, DBP, and MAP responses to high sodium (P values
      <0.0001) and DBP response to low sodium (P value = 0.002). Participants
      homozygous for the variant A allele of this marker had SBP, DBP, and MAP
      responses (95% confidence interval) to high salt of 1.6 (-1.8, 4.9), -0.8 (-5.6,
      4.0), and -0.1 (-4.0, 3.9) mm Hg, respectively, vs. corresponding responses of
      4.6 (2.5, 6.6), 1.7 (-0.2, 3.6), and 2.7 (0.9, 4.4) mm Hg, respectively, for
      those who were heterozygous or homozygous for the G allele. In addition,
      participants with at least one copy of the A allele of SNP rs1129649 of the GNB3
      gene had significantly decreased MAP response to low salt compared to homozygotes
      for the C allele (P value = 0.004) with responses of -3.4 (-3.8, -3.0) vs. -4.2 (
      4.6, -3.8) mm Hg, respectively. CONCLUSIONS: These data support a role for the
      ADD1 and GNB3 genes in BP salt sensitivity. Future studies aimed at replicating
      these novel findings are warranted.

PMID- 19574960
TI  - Augmentation index relates to progression of aortic disease in adults with Marfan
      syndrome.
AB  - BACKGROUND: Noninvasive applanation tonometry (APT) is useful to assess aortic
      stiffness and pulse wave reflection. Moreover, APT can predict outcome in many
      conditions such as arterial hypertension. In this study, we test whether APT
      measurements relate to progression of aortic disease in Marfan syndrome (MFS).
      METHODS: We performed APT in 50 consecutive, medically treated adults with MFS
      (19 men and 31 women aged 32 +/- 13 years), who had not undergone previous
      cardiovascular surgery. During 22 +/- 16 months of follow-up, 26 of these
      patients developed progression of aortic disease, which we defined as progression
      of aortic root diameters >or=5 mm/annum (18 individuals), aortic surgery >or=3
      months after APT (seven individuals), or onset of acute aortic dissection any
      time after APT (one individual). RESULTS: Univariate Cox regression analysis
      suggested an association of aortic disease progression with age (P = 0.001),
      total cholesterol levels (P = 0.04), aortic root diameter (P = 0.007), descending
      aorta diameter (P = 0.01), aortic root ratio (P = 0.02), and augmentation index
      (AIx@HR75; P < 0.006). Multivariate Cox regression analysis confirmed an
      independent impact on aortic disease progression exclusively for baseline aortic
      root diameters (hazard ratio = 1.347; 95% confidence interval (CI) 1.104-1.643; P
      = 0.003) and AIx@HR75 (hazard ratio = 1.246; 95% CI 1.029-1.508; P = 0.02). In
      addition, Kaplan-Meier survival curve analysis illustrated significantly lower
      rates of aortic root disease progression both with lower AIx@HR75 (P = 0.025) and
      with lower pulse wave velocity (PWV) values (P = 0.027). CONCLUSIONS: We provide
      evidence that APT parameters relate to aortic disease progression in medically
      treated patients with MFS. We believe that APT has a potential to improve risk
      stratification in the clinical management of MFS patients.

PMID- 19574958
TI  - Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
AB  - The recognition of bacterial lipoproteins by toll-like receptor (TLR) 2 is
      pivotal for inflammation initiation and control in many bacterial infections.
      TLR2-dependent signalling is currently believed to essentially require both
      adaptor proteins MyD88 (myeloid differentiation primary response gene 88) and
      Mal/TIRAP (MyD88-adapter-like/TIR-domain-containing adaptor protein). TLR2
      dependent, but MyD88-independent responses have not been described yet. We report
      here on a novel-signalling pathway downstream of TLR2, which does not adhere to
      the established model. On stimulation of the TLR2/6 heterodimer with diacylated
      bacterial lipoproteins, Mal directly interacts with the regulatory subunit of
      phosphoinositide 3-kinase (PI3K), p85alpha, in an inducible fashion. The Mal
      p85alpha interaction drives PI3K-dependent phosphorylation of Akt,
      phosphatidylinositol(3,4,5)P3 (PIP(3)) generation and macrophage polarization.
      MyD88 is not essential for PI3K activation and Akt phosphorylation; however,
      cooperates with Mal for PIP(3) formation and accumulation at the leading edge. In
      contrast to TLR2/6, TLR2/1 does not require Mal or MyD88 for Akt phosphorylation.
      Hence, Mal specifically connects TLR2/6 to PI3K activation, PIP(3) generation and
      macrophage polarization.

PMID- 19574961
TI  - Effect of metformin on weight gain during antihypertensive treatment with a beta
      blocker in Chinese patients.
AB  - BACKGROUND: Overweight and obesity are associated with cardiovascular disease
      (CVD). This study was designed to investigate whether combined use of
      nitrendipine and atenolol has any effect on body weight (BW) and whether
      metformin can prevent antihypertensive medication-induced weight gain and has any
      effect on blood glucose (BG). METHODS: Included in the present study were 94
      hypertensive patients with a body mass index (BMI) > or =25 kg/m(2), of whom 45
      patients were treated with nitrendipine plus atenolol (N/A group), and the
      remaining 49 patients were treated with nitrendipine, atenolol, and metformin
      (N/A/M group). The mean follow-up duration was 14 months. BW and glucose
      tolerance were measured. RESULTS: In N/A group, BW and fasting BG significantly
      increased from 73.5 +/- 9.6 kg to 74.2 +/- 9.7 kg (P < 0.05) and from 94.2 +/-
      10.5 mg/dl to 97.9 +/- 11.3 mg/dl (P < 0.01), respectively, whereas postprandial
      BG did not change significantly. In N/A/M group, BW slightly decreased from 72.7
      +/- 10.1 kg to 72.3 +/- 10.2 kg (P = 0.30), and fasting BG did not change
      significantly (93.5 +/- 10.4 mg/dl vs. 92.7 +/- 10.2 mg/dl, P = 0.59), whereas 2
      h postprandial BG significantly decreased from 133.7 +/- 30.5 mg/dl to 124.0 +/-
      29.6 mg/dl (P < 0.05). Furthermore, a significant difference was observed in
      difference value of BW before and after treatment between the two groups (0.7
      (95% confidence interval, 0.1-1.3) kg in N/A group vs. -0.4 (95% confidence
      interval, -1.3 to 0.4) kg in N/A/M group, P < 0.05). CONCLUSIONS: Combination
      therapy of nitrendipine and atenolol may significantly increase BW and fasting BG
      in overweight or obese patients with hypertension. Metformin may prevent BW gain
      and improve BG levels in hypertensive patients who received combination therapy
      of nitrendipine and atenolol.

PMID- 19574962
TI  - Association of ornithine transcarbamylase gene polymorphisms with hypertension
      and coronary artery vasomotion.
AB  - BACKGROUND: Previous studies have suggested that the activity of enzymes involved
      in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion,
      and hypertension. Our aim was to determine whether hypertension and coronary
      vasomotion could be associated with polymorphisms within the ornithine
      transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme
      of the urea cycle. METHODS: Among 11 OTC polymorphisms that were originally
      selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409
      and the independent SNP rs1800321 were tested for association with hypertension
      in two independent population samples recruited in Northern (Multinational
      MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, n
      = 1,138) and Western (Etude du Vieillissement Arteriel (EVA) study, n = 1,166)
      France. The vasomotor response of coronary arteries to methylergonovine maleate
      and isosorbide dinitrate was also evaluated in an independent sample (the
      vasomotion study, n = 121). RESULTS: In males, the frequency of the rs5963409
      minor allele was consistently higher in hypertensive (HT) than in normotensive
      subjects in the MONICA and EVA studies. In the combined sample, the rs5963409
      minor allele was associated with an increased risk of hypertension (odds ratio
      (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This
      association was independent of classical confounding factors. Consistently,
      rs5963409 minor allele was associated with a greater susceptibility to
      vasoconstriction in response to methylergonovine maleate (P = 0.0072). In
      contrast, no significant association between rs5963409 and hypertension could be
      detected in females. CONCLUSION: Our results suggest that the OTC rs5963409
      polymorphism may be associated with hypertension and coronary vasomotion in
      males.

PMID- 19574964
TI  - Physicians and health-care reform: rolling up our sleeves or rolling the dice?

PMID- 19574965
TI  - Misdiagnosis of autoimmune pancreatitis: a caution to clinicians.
AB  - Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas
      that is increasingly encountered worldwide. It has generated considerable
      interest, in part because the inflammatory process usually responds dramatically
      to corticosteroid therapy. The most common presentation mimics that of pancreatic
      cancer; thus, a correct diagnosis of AIP can avoid major surgery. However, the
      diagnosis is challenging, because its incidence is far lower than that of the
      diseases it mimics and there is no single diagnostic clinical feature or test
      that can identify the full spectrum of AIP. Therefore, we are increasingly
      encountering patients misdiagnosed as having AIP. The misdiagnosis typically
      occurs in three scenarios: (i) treatment of pancreatic or biliary malignancy with
      corticosteroids and/or immunomodulators, (ii) treatment of chronic abdominal pain
      with corticosteroids and/or immunomodulators, or (iii) performance of operative
      resection for autoimmune disease. Our purpose is to highlight this growing
      clinical problem and to reinforce the use of published guidelines for the
      diagnosis and management of AIP.

PMID- 19574966
TI  - Statistical graphics in AJG: save the ink for the information.

PMID- 19574967
TI  - Eder-Puestow "stringless" dilators.

PMID- 19574968
TI  - Time trends and impact of upper and lower gastrointestinal bleeding and
      perforation in clinical practice.
AB  - OBJECTIVES: Changing patterns in medical practice may contribute to temporal
      changes in the incidence of upper and lower gastrointestinal (GI) complications.
      There are limited data on the incidence of lower GI complications in clinical
      practice and most studies that have been done have serious methodological
      limitations to inferring the actual burden of this problem. The aims of this
      study were to analyze time trends of hospitalizations resulting from GI
      complications originating both from the upper and lower GI tract in the general
      population, and to determine the risk factors, severity, and clinical impact of
      these GI events. METHODS: This was a population-based study of patients
      hospitalized because of GI complications in 10 general hospitals between 1996 and
      2005 in Spain. We report the age- and gender-specific rates, estimate the
      regression coefficients of the upper and lower GI event trends, and evaluate the
      severity and associated risk factors. GI hospitalization charts were validated by
      an independent review of large random samples of unspecific and specific codes
      distributed among all hospitals and study years. RESULTS: Upper GI complications
      fell from 87/100,000 persons in 1996 to 47/100,000 persons in 2005, whereas lower
      GI complications increased from 20/100,000 to 33/100,000. Overall, mortality
      rates decreased, but the case fatality remained constant over time. Lower GI
      events had a higher mortality rate (8.8 vs. 5.5%), a longer hospitalization
      (11.6+/-13.9 vs. 7.9+/-8.8 days), and higher resource utilization than did upper
      GI events. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) without
      concomitant proton pump inhibitor was more frequently recorded among upper GI
      complications than among lower GI complications. When comparing upper GI events
      with lower GI events, we found that male gender (adjusted odds ratio (OR): 1.94;
      95% confidence interval (CI): 1.70-2.21), and recorded NSAID use (OR: 1.92; 95%
      CI: 1.60-2.30) were associated to a greater extent with upper GI events, whereas
      older age (OR: 0.83; 95% CI: 0.77-0.89), number of comorbidities (OR: 0.91; 95%
      CI: 0.86-0.96), and having a diagnosis in recent years (OR: 0.92; 95% CI: 0.90
      0.94) were all associated to a greater extent with lower GI events than with
      upper GI events after adjusting for age, sex, hospitalization, and discharge
      year. CONCLUSIONS: Over the past decade, there has been a progressive change in
      the overall picture of GI events leading to hospitalization, with a clear
      decreasing trend in upper GI events and a significant increase in lower GI
      events, causing the rates of these two GI complications to converge. Overall,
      mortality has also decreased, but the in-hospital case fatality of upper or lower
      GI complication events has remained constant. It will be a challenge to improve
      future care in this area unless we develop new strategies to reduce the number of
      events originating in the lower GI tract, as well as reducing their associated
      mortality.

PMID- 19574969
TI  - Doc, can I drive home?
AB  - Non-anesthesiologist-administered propfol (NAAP) sedation for endoscopic
      procedures remains controversial despite the overwhelming evidence that with
      proper training and patient selection, NAAP is safe and results in improved time
      to sedation and recovery when compared with standard sedation with a combination
      of an opioid and benzodiazepine. Emerging data suggest that NAAP also results in
      an improved psychomotor recovery. Can our patients return to meaningful tasks
      such as driving with NAAP after recovery in the endoscopy suite?

PMID- 19574972
TI  - The influence of timing of colonoscopy on adenoma detection: is timing
      everything?
AB  - Colorectal cancer is a common disease in the United States. The majority of
      sporadic colorectal cancers develop from adenomatous polyps. In the United
      States, the incidence of colorectal cancer is declining, most likely because of
      colonoscopic polypectomy. Adenoma detection rate is affected by the quality of
      prep, careful mucosal inspection, and withdrawal time. In this issue of the
      Journal, there is intriguing evidence that the timing of colonoscopy, morning vs.
      afternoon, affects adenoma detection rate. Physician fatigue is postulated as a
      factor leading to lower polyp detection rates in the afternoon compared with the
      morning. Further, prospective studies are needed to confirm these findings and
      determine the effect on clinical practice.

PMID- 19574976
TI  - Liver diseases and venous thromboembolism.

PMID- 19574977
TI  - Duodenal intraepithelial lymphocytosis: celiac disease or not?

PMID- 19574978
TI  - The genetics of alcoholic liver disease: better patient group definition is
      required.

PMID- 19574981
TI  - NAFLD and cardiovascular risk: direct evidence for the tale of two ages.

PMID- 19574982
TI  - Portal vein tumor thrombosis revascularization during sorafenib treatment for
      hepatocellular carcinoma.

PMID- 19574983
TI  - Distinguishing between anti-neutrophil cytoplasmic antibody patterns in
      inflammatory bowel disease: is the "atypical pattern" adding more information?

PMID- 19574984
TI  - Medium- and small-vessel vasculitis with large bowel infarction in systemic lupus
      erythematosus: a case report.

PMID- 19574985
TI  - "Comment on a retraction": author response.

PMID- 19574991
TI  - Factors which influence working patterns of orthodontists in the United Kingdom.
AB  - OBJECTIVE: To describe factors which influence the current working patterns of
      orthodontists in the United Kingdom. DESIGN AND SETTING: A cross-sectional postal
      questionnaire to orthodontic specialists in the United Kingdom. SUBJECTS: All
      those on the specialist list in orthodontics held by the General Dental Council
      in 2006-2007. MATERIALS AND METHODS: The data gathered included demographic
      details (gender, ethnicity, age, professional status and number of children),
      calendar year of achieving professional qualifications and current working
      patterns, together with details of any career breaks taken and geographical
      location of work. RESULTS: The response rate was 81.5%. Male and female
      orthodontists were seen to have different working patterns. The difference was
      statistically significant with male orthodontists undertaking clinical work on
      average 1.5 sessions more per week than their female colleagues. The calendar
      year of completion of undergraduate studies and the number of children an
      orthodontist has can significantly affect the number of clinical sessions they
      work each week. In recent years it has been observed that there is greater ethnic
      diversity among the workforce but ethnic origin appeared to have a minimal effect
      on the number of clinical sessions worked each week. The amount and length of
      career breaks taken by female orthodontists was greater than their male
      colleagues. In addition, there continues to be an uneven distribution of
      orthodontists throughout the United Kingdom. CONCLUSION: Many factors influence
      the current working patterns of orthodontists in the United Kingdom. However, it
      may be the inequitable regional distribution of orthodontists throughout the
      United Kingdom which is of greatest significance to orthodontic workforce
      planning for the future.

PMID- 19574992
TI  - The effect of transmucosal 0.2 mg/kg midazolam premedication on dental anxiety,
      anaesthetic induction and psychological morbidity in children undergoing general
      anaesthesia for tooth extraction.
AB  - BACKGROUND: The project aims were to evaluate the benefit of transmucosal
      midazolam 0.2 mg/kg pre-medication on anxiety, induction behaviour and
      psychological morbidity in children undergoing general anaesthesia (GA)
      extractions. METHOD: One hundred and seventy-nine children aged 5-10 years (mean
      6.53 years) participated in this randomised, double blind, placebo-controlled
      trial. Ninety children had midazolam placed in the buccal pouch. Dental anxiety
      was recorded preoperatively and 48 hours later using a child reported MCDAS-FIS
      scale. Behaviour at anaesthetic induction was recorded and psychological
      morbidity was scored by the parent using the Rutter Scale preoperatively and
      again one week later. Subsequent dental attendance was recorded at one, three and
      six months after GA. RESULTS: While levels of dental anxiety did not reduce
      overall, the most anxious patients demonstrated a reduction in anxiety after
      receiving midazolam premedication (p = 0.01). Neither induction behaviour nor
      psychological morbidity improved. Irrespective of group, parents reported less
      hyperactive (p = 0.002) and more pro-social behaviour (p = 0.002) after the
      procedure; older children improved most (p = 0.048). Post-GA dental attendance
      was poor and unaffected by premedication. CONCLUSION: 0.2 mg/kg buccal midazolam
      provided some evidence for reducing anxiety in the most dentally anxious
      patients. However, induction behaviour, psychological morbidity and subsequent
      dental attendance were not found to alter.

PMID- 19574993
TI  - Cholinergic deficiency involved in vascular dementia: possible mechanism and
      strategy of treatment.
AB  - Vascular dementia (VaD) is a progressive neurodegenerative disease with a high
      prevalence. Several studies have recently reported that VaD patients present
      cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be
      closely related to the pathophysiology of cognitive impairment. Moreover,
      cholinergic therapies have shown promising effects on cognitive improvement in
      VaD patients. The precise mechanisms of these cholinergic agents are currently
      not fully understood; however, accumulating evidence indicates that these drugs
      may act through the cholinergic anti-inflammatory pathway, in which the efferent
      vagus nerve signals suppress pro-inflammatory cytokine release and inhibit
      inflammation, although regulation of oxidative stress and energy metabolism,
      alleviation of apoptosis may also be involved. In this paper, we provide a brief
      overview of the cholinergic treatment strategy for VaD and its relevant
      mechanisms of anti-inflammation.Acta Pharmacologica Sinica (2009) 30: 879-888;
      doi: 10.1038/aps.2009.82.

PMID- 19574994
TI  - Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a
      neuroprotective effect on cortical neurons in vitro.
AB  - AIM: To understand the mechanism of the transactivation of the epidermal growth
      factor receptor (EGFR) mediated by the adenosine A(1) receptor (A(1)R). METHODS:
      Primary cultured rat cortical neurons subjected to oxygen-glucose deprivation
      (OGD) and HEK293/A(1)R cells were treated with the A(1)R-specific agonist N(6)
      cyclopentyladenosine (CPA). Phospho-EGFR, Akt, and ERK1/2 were observed by
      Western blot. An interaction between EGFR and A(1)R was detected using
      immunoprecipitation and immunocytochemistry. RESULTS: The A(1)R agonist CPA
      causes protein kinase B (Akt) activation and protects primary cortical neurons
      from oxygen-glucose deprivation (OGD) insult. A(1)R and EGFR co-localize in the
      membranes of neurons and form an immunocomplex. A(1)R stimulation induces
      significant EGFR phosphorylation via a PI3K and Src kinase signaling pathway;
      this stimulation provides a neuroprotective effect in cortical neurons. CPA leads
      to sustained phosphorylation of extracellularly regulated kinases 1 and 2
      (ERK1/2) in cortical neurons, but only to transient phosphorylation in HEK
      293/A(1)R cells. The response to the A(1)R agonist is mediated primarily through
      EGFR transactivation that is dependent on pertussis toxin (PTX)-sensitive G(i)
      protein and metalloproteases in HEK 293/A(1)R. CONCLUSION: A(1)R-mediated EGFR
      transactivation confers a neuroprotective effect in primary cortical neurons. PI3
      kinase and Src kinase play pivotal roles in this response.Acta Pharmacologica
      Sinica (2009) 30: 889-898; doi: 10.1038/aps.2009.80.

PMID- 19574996
TI  - Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine (NAC).
AB  - AIM: To investigate the effect of N-acetylcysteine (NAC), a potent antioxidant,
      on neuron differentiation of cultured mouse embryonic stem cells (ESCs) induced
      by retinoic acid (RA) in vitro. Superior cervical ganglion (SCG) neurons were
      used to study the effect of NAC on neuritogenesis. METHODS: Immunoblotting was
      performed to detect the expression of microtubule-associated protein 2 (MAP2).
      MTT assays were used to determine cell viability. Cell death was estimated with
      trypan blue exclusion and Hoechst 33342 staining. Immunocytochemical analysis was
      carried out to identify neurons. RESULTS: We obtained a high percentage of MAP2
      positive neurons derived from embryoid bodies (EBs) induced by RA by
      administering 1 mmol/L NAC at differentiation day 0. On differentiation day 8,
      the expression of MAP2 protein was strongly upregulated in the presence of NAC.
      NAC promoted neuron differentiation of ES cells in a dose- and time-dependent
      manner. Notably, NAC suppressed cell death caused by RA during neuron
      differentiation. In addition, neurite extension of SCG neurons was greatly
      stimulated in the presence of NAC. CONCLUSION: These results show that NAC
      enhanced both neuron differentiation and neuritogenesis, suggesting that it may
      be used in the development of novel therapeutic approaches targeting neuron loss
      and neurite dystrophy in neurodegenerative diseases.Acta Pharmacologica Sinica
      (2009) 30: 907-912; doi: 10.1038/aps.2009.72.

PMID- 19574995
TI  - Liquiritigenin inhibits Abeta(25-35)-induced neurotoxicity and secretion of
      Abeta(1-40) in rat hippocampal neurons.
AB  - AIM: To examine whether liquiritigenin, a newly found agonist of selective
      estrogen receptor-beta, has neuroprotective activity against beta-amyloid peptide
      (Abeta) in rat hippocampal neurons. METHODS: Primary cultures of rat hippocampal
      neurons were pretreated with liquiritigenin (0.02, 0.2, and 2 micromol/L) prior
      to Abeta(25-35) exposure. Following treatment, viability of the cells was
      measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis
      and by a lactate dehydrogenase activity-based cytotoxicity assay. Intracellular
      Ca(2+) concentration ([Ca(2+)](i)) and levels of reactive oxygen species (ROS),
      as well as apoptotic rates, were determined. Our studies were extended in tests
      of whether liquiritigenin treatment could inhibit the secretion of Abeta(1-40) as
      measured using an ELISA method. In order to analyze which genes may be involved,
      we used a microarray assay to compare gene expression patterns. Finally, the
      levels of specific proteins related to neurotrophy and neurodenegeration were
      detected by Western blotting. RESULTS: Pretreated neurons with liquiritigenin in
      the presence of Abeta(25-35) increased cell viability in a concentration
      dependent manner. Liquiritigenin treatment also attenuated Abeta(25-35)-induced
      increases in [Ca(2+)](i) and ROS level and decreased the apoptotic rate of
      neurons. Some genes, including B-cell lymphoma/leukemia-2 (Bcl-2), neurotrophin 3
      (Ntf-3) and amyloid beta (A4) precursor protein-binding, family B, member 1 (Apbb
      1) were regulated by liquiritigenin; similar results were shown at the protein
      level by Western blotting. CONCLUSION: Our results demonstrate that
      liquiritigenin exhibits neuroprotective effects against Abeta(25-35)-induced
      neurotoxicity and that it can decrease the secretion of Abeta(1-40). Therefore,
      liquiritigenin may be useful for further study as a prodrug for treatment of
      Alzheimer's disease.Acta Pharmacologica Sinica (2009) 30: 899-906; doi:
      10.1038/aps.2009.74.

PMID- 19574997
TI  - Silencing neuroglobin enhances neuronal vulnerability to oxidative injury by down
      regulating 14-3-3gamma.
AB  - AIM: To explore the protective role and mechanism of endogenous neuroglobin (Ngb)
      in neuronal cells under oxidative stress. METHODS: A stable N2a neuroblastoma
      cell line expressing the Ngb-siRNA plasmid (N2a/Ngb-siRNA) was established by
      neomycin screening. Reverse transcription (RT)-PCR and Western blot analysis were
      used to detect Ngb gene and protein levels. Hydrogen peroxide was used to induce
      oxidative stress in N2a cells. Cytotoxicity and cell viability were measured by
      lactate dehydrogenase (LDH) and WST-8 assays. Apoptotic cells were detected by
      Hoechst staining. RESULTS: Cotransfection of Ngb-siRNA with Ngb-GFP plasmids
      suppressed the expression of Ngb-GFP in N2a cells. RT-PCR and Western blot
      analysis showed that the expression of endogenous Ngb was successfully knocked
      down to about 20% in N2a/Ngb-siRNA cells compared with control cells. A WST-8
      assay demonstrated that viability was significantly decreased in N2a/Ngb-siRNA
      cells and N2a cells transiently transfected with Ngb-siRNA plasmids compared with
      controls following hydrogen peroxide treatment. An LDH assay demonstrated a time
      dependent increase in the death of Ngb-siRNA-transfected N2a cells following
      hydrogen peroxide treatment. Hoechst staining demonstrated that the quantity of
      apoptotic cells among N2a/Ngb-siRNA cells following hydrogen peroxide treatment
      significantly increased compared with controls. In N2a/Ngb-siRNA cells, the
      expression level of activated caspase-3 significantly increased, whereas the
      expression of 14-3-3gamma decreased compared with that of N2a/vec cells.
      Transfection of 14-3-3gamma plasmids significantly enhanced the viability of
      N2a/Ngb-siRNA cells following hydrogen peroxide treatment compared with vector
      controls. CONCLUSION: Ngb contributes to neuronal defensive machinery against
      oxidative injuries by regulating 14-3-3gamma expression.Acta Pharmacologica
      Sinica (2009) 30: 913-918; doi: 10.1038/aps.2009.70.

PMID- 19574998
TI  - RNA interference-mediated downregulation of Beclin1 attenuates cerebral ischemic
      injury in rats.
AB  - AIM: To test the role of the Beclin 1-dependent autophagy pathway in brain damage
      during cerebral ischemia. METHODS: Focal cerebral ischemia was established in
      rats using a middle cerebral artery occlusion (MCAO) model. A lentiviral vector
      associated RNA interference (RNAi) system was stereotaxically injected into the
      ipsilateral lateral ventricle to reduce Beclin1 expression. We measured the
      ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis,
      all of which could be modulated by Beclin1 RNAi. RESULTS: On the 14th day after
      MCAO, Beclin1 downregulation by RNAi increased the population of neural
      progenitor cells (BrdU(+)-DCX(+)), newborn immature cells (BrdU(+)-Tuj-1(+)) and
      mature neurons (BrdU(+)-MAP-2(+)), and reduced the apoptosis of immature neurons
      (caspase-3(+)-DCX(+) and caspase-3(+)-Tuj-1(+)) surrounding the ischemic core of
      the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclin1
      decreased infarct volume and inhibited histological injury and neurological
      deficits. CONCLUSION: RNAi-mediated downregulation of Beclin1 improves outcomes
      after transient MCAO.Acta Pharmacologica Sinica (2009) 30: 919-927; doi:
      10.1038/aps.2009.79.

PMID- 19574999
TI  - Regulation of gap-junction protein connexin 43 by beta-adrenergic receptor
      stimulation in rat cardiomyocytes.
AB  - AIM: beta-adrenergic receptor (beta-AR) agonists are among the most potent
      factors regulating cardiac electrophysiological properties. Connexin 43 (Cx43),
      the predominant gap-junction protein in the heart, has an indispensable role in
      modulating cardiac electric activities by affecting gap-junction function. The
      present study investigates the effects of short-term stimulation of beta-AR
      subtypes on Cx43 expression and gap junction intercellular communication (GJIC)
      function. METHODS: The level of Cx43 expression in neonatal rat cardiomyocytes
      (NRCM) was detected by a Western blotting assay. The GJIC function was evaluated
      by scrape loading/dye transfer assay. RESULTS: Stimulation of beta-AR by the
      agonist isoproterenol for 5 min induces the up-regulation of nonphosphorylated
      Cx43 protein level, but not total Cx43. Selective beta(2)-AR inhibitor ICI
      118551, but not beta(1)-AR inhibitor CGP20712, could fully abolish the effect.
      Moreover, pretreatment with both protein kinase A inhibitor H89 and G(i) protein
      inhibitor pertussis toxin also inhibited the isoproterenol-induced increase of
      nonphosphorylated Cx43 expression. Isoproterenol-induced up-regulation of
      nonphosphorylated Cx43 is accompanied with enhanced GJIC function. CONCLUSION:
      Taken together, beta(2)-AR stimulation increases the expression of
      nonphosphorylated Cx43, thereby enhancing the gating function of gap junctions in
      cardiac myocytes in both a protein kinase A- and G(i)-dependent manner.Acta
      Pharmacologica Sinica (2009) 30: 928-934; doi: 10.1038/aps.2009.92.

PMID- 19575000
TI  - Alteration of airway responsiveness mediated by receptors in ovalbumin-induced
      asthmatic E3 rats.
AB  - AIM: Airway hyperresponsiveness is a constant feature of asthma. The aim of the
      present study was to investigate airway hyperreactivity mediated by contractile
      and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.
      METHODS: Asthmatic E3 rats were prepared by intraperitoneal injection with
      OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA
      PBS two weeks later. The myograph method was used to measure the responses of
      constriction and dilatation in the trachea, main bronchi and lobar bronchi.
      RESULTS: In asthmatic E3 rats, beta(2) adrenoceptor-mediated relaxation of airway
      smooth muscle pre-contracted with 5-HT was inhibited, and there were no obvious
      difference in relaxation compared with normal E3 rats. Contraction of lobar
      bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea
      or main bronchi. Airway contractions mediated by the endothelin (ET)(A) receptor,
      ET(B) receptor and M(3) muscarinic receptor were augmented, and the augmented
      contraction was most obvious in lobar bronchi. The order of efficacy of
      contraction for lobar bronchi induced by agonists was ET-1, sarafotoxin 6c>ACh>5
      HT. OX8 (an antibody against CD8(+) T cells) strongly shifted and OX35 (an
      antibody against CD4(+) T cells) modestly shifted isoprenaline-induced
      concentration-relaxation curves in a nonparallel fashion to the left with an
      increased R(max) in asthmatic rats and sarafotoxin 6c-induced concentration
      contractile curves to the right with a decreased E(max). CONCLUSION: The
      inhibition of airway relaxation and the augmentation of contraction mediated by
      receptors contribute to airway hyperresponsiveness and involve CD8(+) and CD4(+)
      T cells.Acta Pharmacologica Sinica (2009) 30: 965-972; doi: 10.1038/aps.2009.61.

PMID- 19575001
TI  - NAC is associated with additional alleviation of lung injury induced by invasive
      pulmonary aspergillosis in a neutropenic model.
AB  - AIM: Neutropenic individuals are at high risk for invasive pulmonary
      aspergillosis (IPA), a life-threatening infection. To evaluate the therapeutic
      potential of antioxidants, IPA was induced in neutropenic mice and the effect of
      N-acetyl-l-cysteine (NAC) on oxidative stress levels and lung injury was
      analyzed. METHODS: Mice were pretreated with three daily intraperitoneal
      injections of 150 mg/kg cyclophosphamide, followed by intratracheal inoculation
      with 4.5x10(6) conidia of Aspergillus fumigatus. The infected mice were then
      randomly assigned to an amphotericin B (AMB) group, an AMB plus NAC group, or an
      untreated control (C) group. In each group, the duration of treatment was 24, 48,
      or 72 h, and activities such as appearance, feeding, and dermal temperature were
      observed throughout the experiment. Sera and lung tissues were collected and
      analyzed by quantitative enzyme-linked immunosorbent assay (ELISA) for total
      protein, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor
      alpha (TNF-alpha), and interleukin-10 (IL-10) levels. The wet/dry weight ratio of
      the lung was also calculated and lung sections were stained with hematoxylin
      eosin for pathological examination and with methenamine silver stain for fungus
      detection. RESULTS: Compared with the mice untreated with NAC, mice in the AMB
      plus NAC group had increased SOD and reduced MDA levels both systemically and
      locally at 24, 48, and 72 h after inoculation with conidia. NAC treatment also
      decreased the pulmonary protein content at 48 and 72 h and the lung wet/dry
      weight ratio at 24 and 48 h. Additionally, NAC enhanced pulmonary production of
      TNF-alpha and IL-10 at 24 h and 48 h. CONCLUSION: In combination with antifungal
      therapy, NAC treatment can alleviate oxidative stress and lung injury associated
      with IPA in neutropenic mice.Acta Pharmacologica Sinica (2009) 30: 980-986; doi:
      10.1038/aps.2009.83.

PMID- 19575002
TI  - Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium
      induced colitis in mice.
AB  - AIM: To investigate the effect of balsalazine treatment on intestinal mucosal
      permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the
      mechanism of the balsalazine-induced changes. METHODS: Experimental colitis was
      induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was
      administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease
      activity index (DAI) score was evaluated and colon tissue was collected for the
      assessment of histological changes. The amount of malondialdehyde (MDA) in the
      colon was determined, along with the activity of myeloperoxidase (MPO),
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the
      small intestine was collected to determine the levels of tumor necrosis factor
      (TNF)-alpha and interferon (IFN)-gamma. The mucosa was ultrastructurally examined
      with transmission electron microscopy and intestinal permeability was assayed
      using Evans blue. RESULTS: Balsalazine was found to reduce the DAI score and the
      histological index (HI) score, decrease the MDA content and the activity of MPO,
      and increase the activity of SOD and GSH-Px in colitis mice. At the same time,
      balsalazine ameliorated microvillus and tight junction structure, resulting in a
      decrease in the amount of Evans blue permeating into the intestinal wall and the
      levels of TNF-alpha and IFN-gamma in colitis mice. CONCLUSION: In colitis mice,
      the anti-colitis effect of balsalazine results in a decrease in intestinal
      mucosal permeability. The mechanism of this effect is partly associated with
      balsalazine's antioxidative and anti-inflammatory effects.Acta Pharmacologica
      Sinica (2009) 30: 987-993; doi: 10.1038/aps.2009.77.

PMID- 19575003
TI  - Expression of Rho GDIalpha in rat osteoblasts intermittently exposed to
      parathyroid hormone in vitro and in vivo.
AB  - AIM: To investigate the mechanism of the bone-forming effects of intermittent
      parathyroid hormone (PTH) administration and to search for novel molecules of
      bone anabolism via the PTH signaling pathway. METHODS: Primary cultures of rat
      osteoblasts (ROBs) were divided into an intermittent PTH-treated group (Itm) and
      a control group (Ctr). Imitating the pharmacokinetics of intermittent PTH
      administration in vivo, the ROBs in the Itm group were exposed to PTH for 6 h in
      a 24-h incubation cycle, and the ROBs in the Ctr group were exposed to vehicle
      for the entire incubation cycle. The cells were collected at 6 h and 24 h of the
      final cycle, and the proteins in the Itm and Ctr groups were analyzed by two
      dimensional electrophoresis (2-DE) coupled with peptide mass fingerprinting and
      matrix assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) to detect proteins that were differentially expressed. The
      proteins with the most significant changes in vitro were validated by
      immunohistochemistry (IHC) in a rat model. RESULTS: The proteomics analysis
      indicated that a total of 26 proteins were up- or down-regulated in the Itm group
      compared with the Ctr group at 6 h and 24 h; among these, 15 proteins were
      successfully identified. These proteins mainly belong to the cytoskeleton and
      molecular chaperone protein families, and most of these have anti-apoptotic
      effects in various cells. Rho GDP-dissociation inhibitor alpha (RhoGDIalpha) and
      vimentin were the most significantly changed proteins. Further studies by IHC
      showed that the expression of RhoGDIalpha in ROBs was significantly higher in PTH
      treated sham-operated rats than in vehicle-treated sham-operated rats, but the
      difference was not significant between PTH-treated and vehicle-treated OVX rats.
      Vimentin expression was not changed in either PTH-treated sham-operated rats or
      PTH-treated OVX rats. CONCLUSION: Our research suggests that intermittent PTH
      treatment induces changes in expression of many proteins in ROBs in vitro, and it
      results in RhoGDIalpha up-regulation in ROBs both in vitro and in vivo when
      estrogen is present. This up-regulation of RhoGDIalpha may be one of the
      mechanisms underlying the synergistic bone-forming effect of PTH and
      estrogen.Acta Pharmacologica Sinica (2009) 30: 1001-1007; doi:
      10.1038/aps.2009.60.

PMID- 19575004
TI  - Macrophage receptors of polysaccharide isolated from a marine filamentous fungus
      Phoma herbarum YS4108.
AB  - AIM: YCP, a novel (1,4)-alpha-D-glucan, was isolated from the mycelium of the
      marine filamentous fungus Phoma herbarum YS4108. In this work, we investigated a
      YCP-binding cellular receptor expressed by macrophages and the intracellular
      signal transduction pathways involved in YCP-induced macrophage activation.
      METHODS: Fluorescence-labeled YCP (fl-YCP) was prepared using the CDAP-activation
      method. Fluorescence confocal laser microscopy and fluorescence-activated cell
      sorting (FACS) were used to analyze the effect of fl-YCP on macrophages. To
      characterize the properties of the YCP receptor, carbohydrates and antibodies
      were used to inhibit the binding of fl-YCP to macrophages. Moreover, we
      investigated the role of membrane receptors Toll-like receptor 2 (TLR2), Toll
      like receptor 4 (TLR4), Toll-like receptor 6 (TLR6) and complement receptor 3
      (CR3). We also examined the role of the p38 kinase pathway in mediating nitric
      oxide (NO) production. RESULTS: YCP had an in vitro stimulatory effect on the
      release of NO in macrophage, and fl-YCP can bind directly to receptors on the
      surface of macrophages in a time- and dose-dependent manner. Competition studies
      show that LPS, laminarin, anti-TLR4 antibody and anti-CD11b (CR3) antibody could
      inhibit fl-YCP binding to macrophages. Conversely, mannose, anti-TLR2 and anti
      TLR6 antibody could not. Treatment of RAW264.7 cells with YCP resulted in
      significant activation of p38 in a time-dependent manner. The specific p38
      inhibitor SB203580 abrogated YCP-induced NO generation. Treatment of RAW264.7
      cells with anti-TLR4 antibody and anti-CR3 antibody significantly reduced YCP
      induced NO production and p38 activation. CONCLUSION: We have demonstrated that
      YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a
      p38 kinase-dependent manner in macrophages.Acta Pharmacologica Sinica (2009) 30:
      1008-1014; doi: 10.1038/aps.2009.93.

PMID- 19575005
TI  - Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in
      vitro.
AB  - AIM: Arbidol is an immunomodulator that was first developed in Russia. In this
      study, we report the antiviral activity of arbidol against Hantaan virus (HTNV)
      in vitro and in vivo. METHODS: The antiviral activity of arbidol in vitro was
      determined by plaque-forming assay, ranging from 0.5 to 8 microg/mL. To
      investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice
      infected with HTNV were treated with arbidol at 24 h before infection with a 5,
      10 or 20 mg.kg(-1).d(-1), once per day, for 10 days. On day 12 and 28 post
      infection (pi), histopathological changes and viral antigen were detected. On
      days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-alpha
      levels of arbidol-treated animals were determined. RESULTS: Arbidol was found to
      have potent inhibitory activity against HTNV when added in vitro before or after
      viral infection, with a 50% inhibitory concentration (IC(50)) of 0.9 and 1.2
      microg/mL, respectively. The 50% lethal dose (LD(50)) of arbidol for suckling
      mice was 78.42 mg.kg(-1).d(-1). Oral administration of arbidol increased both
      survival rate and mean time to death (MTD). Treatment with arbidol reduced
      histopathological changes, decreased viral load and viral antigen levels, and
      modulated the level of serum TNF-alpha. CONCLUSION: Arbidol has the ability to
      elicit protective antiviral activity against HTNV in vivo and in vitro.Acta
      Pharmacologica Sinica (2009) 30: 1015-1024; doi: 10.1038/aps.2009.53; published
      online 8 June 2009.

PMID- 19575006
TI  - Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor
      growth in mice.
AB  - AIM: To investigate the effects of lidamycin (LDM) on a mouse myeloma cell line
      (SP2/0) and human multiple myeloma cell lines (U266 and SKO-007), and provide the
      basis for the use of LDM in cancer therapy. METHODS: A 3-[4,5-dimethylthiazol-2
      yl]5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]2H-tetrazolium inner salt (MTS)
      assay was used to determine the degree of growth inhibition by the drugs analyzed
      in this study. Cell cycle distribution and analysis were measured by flow
      cytometry combined with propidium iodide (PI) staining. The effects on apoptosis
      were measured by Hoechst 33342 staining and by flow cytometry combined with
      fluorescein-isothiocyanate-Annexin V/propidium iodide (FITC-Annexin V/PI)
      staining. Protein expression was determined by Western blot analysis. In vivo
      antitumor activity was measured using a murine myeloma model in BALB/c mice.
      RESULTS: There was a significant reduction in cell proliferation after treatment
      with LDM. The overall growth inhibition correlated with increased apoptotic cell
      death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N
      terminal kinase (JNK), and cleavage of caspase-3/7 and poly (ADP-ribose)
      polymerase (PARP). LDM markedly suppressed tumor growth in a murine myeloma
      model. CONCLUSION: LDM induces apoptosis in murine myeloma SP2/0 cells as well as
      in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK
      might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM
      demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice.
      Taken together, our data provide some clues for further research of the effects
      of LDM on human multiple myeloma.Acta Pharmacologica Sinica (2009) 30: 1025-1032;
      doi: 10.1038/aps.2009.75.

PMID- 19575007
TI  - Inhibition of autophagy induced by proteasome inhibition increases cell death in
      human SHG-44 glioma cells.
AB  - AIM: The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy
      (autophagy) are two major intracellular pathways for protein degradation. Recent
      studies suggest that proteasome inhibitors may reduce tumor growth and activate
      autophagy. Due to the dual roles of autophagy in tumor cell survival and death,
      the effect of autophagy on the destiny of glioma cells remains unclear. In this
      study, we sought to investigate whether inhibition of the proteasome can induce
      autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells.
      METHODS: The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44
      glioma cells, and the effect of autophagy on the survival of SHG-44 glioma cells
      was investigated using an autophagy inhibitor 3-MA. Cell viability was measured
      by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The
      expression of autophagy related proteins was determined by Western blot. RESULTS:
      MG-132 inhibited cell proliferation, induced cell death and cell cycle arrest at
      G(2)/M phase, and activated autophagy in SHG-44 glioma cells. The expression of
      autophagy-related Beclin-1 and LC3-I was significantly up-regulated and part of
      LC3-I was converted into LC3-II. However, when SHG-44 glioma cells were co
      treated with MG-132 and 3-MA, the cells became less viable, but cell death and
      cell numbers at G(2)/M phase increased. Moreover, the accumulation of acidic
      vesicular organelles was decreased, the expression of Beclin-1 and LC3 was
      significantly down-regulated and the conversion of LC3-II from LC3-I was also
      inhibited. CONCLUSION: Inhibition of the proteasome can induce autophagy in human
      SHG-44 glioma cells, and inhibition of autophagy increases cell death. This
      discovery may shed new light on the effect of autophagy on modulating the fate of
      SHG-44 glioma cells.Acta Pharmacologica Sinica (2009) 30: 1046-1052; doi:
      10.1038/aps.2009.71.

PMID- 19575008
TI  - The antiproliferative effects of somatostatin receptor subtype 2 in breast cancer
      cells.
AB  - AIM: Somatostatin receptor subtype 2 (SSTR2) is the principal mediator of
      somatostatin's (SST) antiproliferative effects on normal and cancer cells.
      Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit
      the proliferation of tumor cells, and, if so, the mechanisms that might be
      involved. METHODS: SSTR2 expression levels were determined by qRT-PCR in several
      tumor cell lines. Then, a plasmid pIRES2-EGFP-SSTR2 (pSIG) was constructed and
      stably transfected into MCF-7 cells (MCF-7/pSIG). After SSTR2 overexpression was
      identified by qRT-PCR, immunofluorescence staining and a receptor binding assay,
      the MCF-7/pSIG cells were analyzed by PI staining for apoptosis and cell cycle
      arrest was tested by flow cytometry for epidermal growth factor receptor (EGFR)
      expression. The EGF-stimulated proliferation of MCF-7 cells was assayed by MTT.
      RESULTS: The human breast cancer cell line MCF-7 expresses a lower level of
      SSTR2, thereby partly accounting for the decreased response to SST. The
      overexpression of SSTR2 in MCF-7 cells resulted in apoptosis, cytostasis and
      G(1)/S cell cycle arrest. Furthermore, the expression of EGFR, together with EGF
      stimulated proliferation, was markedly decreased in the MCF-7/pSIG cells.
      CONCLUSION: Enhanced SSTR2 expression played an antiproliferative role in MCF-7
      cells through inducing apoptosis and G(1)/S cell cycle arrest, and also by
      decreasing EGFR expression, thereby counteracting the growth-stimulating effect
      of EGF. Our data seem to indicate that developing a new therapeutic agent capable
      of upregulating SSTR expression could potentially be a way to block tumor
      progression.Acta Pharmacologica Sinica (2009) 30: 1053-1059; doi:
      10.1038/aps.2009.59.

PMID- 19575009
TI  - Effects of hormone replacement therapy on magnetic resonance imaging of brain
      parenchyma hyperintensities in postmenopausal women.
AB  - AIM: To apply 3.0 magnetic resonance imaging (MRI) to study the effects of long
      term, low dose hormone replacement therapy (HRT) on the brain parenchyma of
      postmenopausal women. METHODS: A total of 155 postmenopausal healthy female
      medical staff members from Peking Union Medical College Hospital were enrolled.
      The HRT group was composed of 71 subjects who had been given a low dose of HRT
      for over 4 years, while 84 women who had never been given HRT were enrolled in
      the control group. The Mini-Mental State Examination (MMSE) was used to evaluate
      mental state, and an Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to detect
      plasma levels of sex hormones. In addition, all participants were subjected to an
      MRI, including axial T2 weighted imaging (T2WI), fluid-attenuated inversion
      recovery (FLAIR), T1 weighted imaging (T1WI, oblique coronal, vertical to the
      hippocampus, slice thickness 3 mm without gaps), and a 3D image of the whole
      brain. RESULTS: The ELISA showed that the plasma level of estradiol in the HRT
      group was significantly higher than that in the control group (P<0.05). No
      differences were observed in the MMSE between the two groups. In participants
      older than 70 years of age, the number of deep white matter hyperintensities
      (DWMHs) in the control group was significantly higher than that in the HRT group
      (P=0.0013); however, in other age subgroups, no statistical differences were
      observed. Finally, no significant difference in periventricular hyperintensity
      (PVH) between the two groups was observed. CONCLUSION: We found that a high
      plasma level of estradiol in postmenopausal women receiving long-term HRT was
      correlated with the survival of brain parenchyma.Acta Pharmacologica Sinica
      (2009) 30: 1065-1070; doi: 10.1038/aps.2009.81.

PMID- 19575010
TI  - The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic
      beta-cell line.
AB  - A previously uncharacterized putative ion channel, NALCN (sodium leak channel,
      non-selective), has been recently shown to be responsible for the tetrodotoxin
      (TTX)-resistant sodium leak current implicated in the regulation of neuronal
      excitability. Here, we show that NALCN encodes a current that is activated by M3
      muscarinic receptors (M3R) in a pancreatic beta-cell line. This current is
      primarily permeant to sodium ions, independent of intracellular calcium stores
      and G proteins but dependent on Src activation, and resistant to TTX. The current
      is recapitulated by co-expression of NALCN and M3R in human embryonic kidney-293
      cells and in Xenopus oocytes. We also show that NALCN and M3R belong to the same
      protein complex, involving the intracellular I-II loop of NALCN and the
      intracellular i3 loop of M3R. Taken together, our data show the molecular basis
      of a muscarinic-activated inward sodium current that is independent of G-protein
      activation, and provide new insights into the properties of NALCN channels.

PMID- 19575011
TI  - CDK9 directs H2B monoubiquitination and controls replication-dependent histone
      mRNA 3'-end processing.
AB  - Post-translational histone modifications have essential roles in controlling
      nuclear processes; however, the specific mechanisms regulating these
      modifications and their combinatorial activities remain elusive. Cyclin-dependent
      kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional
      regulatory proteins, including the RNA polymerase II carboxy-terminal domain.
      Here, we show that CDK9 activity is essential for maintaining global and gene
      associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9
      activity and H2Bub1 help to maintain correct replication-dependent histone
      messenger RNA (mRNA) 3'-end processing. CDK9 knockdown consistently resulted in
      inefficient recognition of the correct mRNA 3'-end cleavage site and led to
      increased read-through of RNA polymerase II to an alternative downstream
      polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during
      transcription with chromatin modifications to control co-transcriptional histone
      mRNA processing.

PMID- 19575012
TI  - Epigenetic reprogramming during wound healing: loss of polycomb-mediated
      silencing may enable upregulation of repair genes.
AB  - Tissue repair is a complex process that requires wound-edge cells to proliferate
      and migrate, which in turn necessitates induction of a large repair
      transcriptome. Epigenetic modifications have emerged as crucial regulators of
      gene expression. Here, we ask whether epigenetic reprogramming might contribute
      to the concerted induction of repair genes by wound-edge cells. Polycomb group
      proteins (PcGs) co-operatively silence genes by laying down repressive marks such
      as histone H3 lysine 27 trimethylation (H3K27me3), which can be removed by
      specific demethylases. We show that PcGs Eed, Ezh2 and Suz12 are significantly
      downregulated during murine skin repair, whereas the newly described demethylases
      Jmjd3 and Utx are markedly upregulated. Correspondingly, we find a striking
      reduction of repressive H3K27me3 in the wound epidermis. Quantitative chromatin
      immunoprecipitation studies have revealed that there is less Eed bound to the
      regulatory regions of two paradigm wound-induced genes, Myc and Egfr, suggesting
      that loss of polycomb-mediated silencing might contribute to the induction of
      repair genes.

PMID- 19575013
TI  - Expression of the Arabidopsis jasmonate signalling repressor JAZ1/TIFY10A is
      stimulated by auxin.
AB  - Plant hormones have pivotal roles in almost every aspect of plant development.
      Over the past decades, physiological and genetic studies have revealed that
      hormone action in plants is determined by complex interactions between hormonal
      signalling pathways. Evidence is accumulating for the existence of crosstalk
      between the auxin and jasmonate (JA) signalling pathways. Recently, the JASMONATE
      ZIM-domain (JAZ) proteins have been identified as the long-sought repressors of
      JA signalling. Here, we show that expression of JAZ1/TIFY10A is not solely
      inducible by JA, but that it is also an early auxin-responsive gene. Furthermore,
      we could show that the auxin-inducible expression of JAZ1/TIFY10A is independent
      of the JA signalling pathway but is controlled by the auxin/indole-3-acetic acid
      auxin response transcription factor signalling pathway. Our results provide
      evidence for the existence of at least two different input signals regarding
      JAZ1/TIFY10A expression and thus support the idea of an intimate molecular
      interplay between auxin and JA signalling.

PMID- 19575014
TI  - Relationship between cerebral blood flow and later cognitive decline in
      hypertensive patients with cerebral small vessel disease.
AB  - Vascular risk factors are thought to be important for dementia. However, there is
      little evidence for a prospective association between cerebral blood flow and the
      risk of cognitive decline. Twenty-seven cognitively intact hypertensive patients
      aged 55 years and older with lacunar infarction or white matter lesions in
      magnetic resonance imaging (MRI) underwent positron emission tomography (PET) to
      measure cerebral blood flow (CBF) and cerebral vascular reactivity (CVR).
      Cognitive function was assessed at baseline and 3 years later with the mini
      mental state examination (MMSE). Patients whose MMSE score fell by more than
      three points were classified as having cognitive decline. Six patients showed
      cognitive decline. Baseline CBF in these patients was significantly lower than
      that of the 21 patients without cognitive decline (31.2+/-2.4 vs. 42.6+/-5.9 ml
      per 100 g min(-1), respectively; P<0.001). A moderate linear association was
      found between CBF and change in MMSE score over a 3-year period (r=0.59,
      P=0.001), not between CBF and baseline MMSE score. In contrast, no association
      between CVR and later cognitive decline was found. This study suggests that
      cerebral hypoperfusion is associated with later cognitive decline.

PMID- 19575015
TI  - Does carotid-ankle vascular index reflect proper vascular distensibility in
      hemodialysis patients?

PMID- 19575016
TI  - Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and
      apoptosis in germ cells.
AB  - In Caenorhabditis elegans, apoptosis in germ cells is mediated by the same core
      apoptotic machinery that controls apoptosis in somatic cells. These include the
      CED-3 caspase, the CED-3 activator CED-4, and the cell death inhibitor CED-9.
      However, germline apoptosis also differs from somatic apoptosis in its
      regulation. We found that CSP-3, a caspase homolog that blocks CED-3
      autoactivation and apoptosis in somatic cells, does not affect apoptosis in germ
      cells. Interestingly, the second C. elegans caspase homolog, CSP-2, shares
      sequence similarity to both catalytic subunits of the CED-3 caspase, and
      surprisingly, contains a stretch of sequence that is almost identical to that of
      CSP-3. Unlike CSP-3 that acts specifically in somatic cells, loss of CSP-2 causes
      increased apoptosis only in germ cells, suggesting that CSP-2 is a germ cell
      specific apoptosis inhibitor. Moreover, like CSP-3, CSP-2 associates with the CED
      3 zymogen and inhibits its autoactivation, but does not inhibit CED-4-induced CED
      3 activation or the activity of the activated CED-3 protease. Thus, two different
      C. elegans caspase homologs use the same mechanism to prevent caspase
      autoactivation and apoptosis in different tissues, suggesting that this could be
      a generally applicable strategy for regulating caspase activation and apoptosis.

PMID- 19575017
TI  - Targeted depletion of BMI1 sensitizes tumor cells to P53-mediated apoptosis in
      response to radiation therapy.
AB  - Overexpression of BMI1 correlates with cancer development, progression, and
      therapy failure; however, the underlying molecular mechanisms remain to be fully
      elucidated. Using the C666-1 nasopharyngeal cancer (NPC) model, the role of BMI1
      in mediating response of NPC cells to radiation therapy (RT) was investigated.
      The results showed a novel radioresistance function for BMI1 in NPC, wherein BMI1
      depletion sensitized NPC cells to RT. Cell cycle analysis and transmission
      electron microscopy (TEM) showed apoptosis as the major mode of cell death, and
      the mitochondria as a primary targeted cellular organelle. Genome-wide microarray
      and pathway analyses revealed that the P53 pathway is a critical mediator of this
      process. Cotransfection with siP53 rescued C666-1 cells from cytotoxicity upon
      BMI1 depletion and RT, thereby corroborating the role for P53. Pretreatment with
      the antioxidant, Trolox, inhibited apoptosis, indicating that production of
      reactive oxygen species (ROS) is also mediating cytotoxicity. In vivo, BMI1
      depletion combined with RT abrogated tumor-forming capacity in SCID mice, showing
      the relevance of this process in a more complex tumor environment. Hence, we show
      a novel role for BMI1 in conferring radioresistance in cancer cells through the
      downregulation of p53-mediated apoptosis. These results suggest a potential
      strategy of BMI1 depletion combined with RT for tumors wherein BMI1 appears to be
      driving disease progression.

PMID- 19575019
TI  - The burdens of digestive diseases.

PMID- 19575018
TI  - Cyclin D1 promotes anchorage-independent cell survival by inhibiting FOXO
      mediated anoikis.
AB  - O-class forkhead box (FOXO) transcription factors are critical regulators of
      diverse cellular processes, including apoptosis, cell-cycle arrest, DNA damage
      repair and oxidative stress resistance. Here, we show that FOXO1 and FOXO3a have
      an essential function in promoting cell detachment-induced anoikis, resistance to
      which is implicated in cancer development and metastasis. In contrast, the
      oncoprotein cyclin D1 inhibits anoikis. We further show that cyclin D1 interacts
      with FOXO proteins and impedes their transcriptional regulatory and anoikis
      promoting functions. This effect of cyclin D1 requires its transcription
      repression domain but is independent of cyclin-dependent kinases CDK4 and CDK6.
      Moreover, we show that cancer-derived mutants of cyclin D1 are much more stable
      than wild-type cyclin D1 under anchorage-independent conditions and possess a
      greater antagonistic effect on FOXO-regulated anoikis and anchorage-independent
      growth of cancer cells. These data suggest that cyclin D1 may have a critical
      function in tumorigenesis and cancer metastasis by inhibiting the anoikis
      promoting function of FOXO proteins.

PMID- 19575020
TI  - Hepatitis: HCV variability, the immune system and resistance to antiviral drugs.

PMID- 19575021
TI  - Stomach: Quadruple therapy for Helicobacter pylori eradication.

PMID- 19575022
TI  - Ulcerative colitis: Natural history--an optimistic message from Norway.

PMID- 19575023
TI  - Surgery: New indications for laparoscopic sigmoidectomy.

PMID- 19575024
TI  - Surgery: Laparoscopy for suspected appendicitis.

PMID- 19575025
TI  - New and experimental therapies for HCV.
AB  - Despite improvements to treatments for HCV infection, almost half of patients
      cannot be cured with standard combination therapy (pegylated interferon alpha and
      ribavirin). The HCV life cycle offers a number of potential targets for molecular
      therapy, and several specifically targeted antiviral therapies for HCV (STAT-Cs)
      are in preclinical and clinical stages of development. Evidence to date suggests
      that monotherapy with any antiviral drug is unlikely to eradicate HCV infection.
      Combination therapy with interferon and ribavirin is necessary for the
      augmentation of antiviral drug activity and/or prevention of drug resistance.
      Results from clinical trials carried out in the past few years on STAT-C agents
      in combination with standard therapy with peginterferon and ribavirin provide
      great promise of higher rates of sustained virological response and, potentially,
      shorter duration of therapy than standard therapy alone achieves. Although
      pegylated interferon and ribavirin are likely to remain a cornerstone of
      therapeutic regimens in the short term, combinations of antiviral drugs of
      different classes, possibly along with novel agents that target host factors and
      modulate viral replication or augment antiviral defenses, offer the eventual
      possibility of interferon-free regimens.

PMID- 19575026
TI  - Hepatosplenic T-cell lymphoma in a patient with Crohn's disease.
AB  - BACKGROUND: A 58-year-old man who had a 35-year history of Crohn's disease
      presented to our IBD center with a disease flare, pararectal fistulas and abscess
      formation. The patient had previously undergone ileocolic resection for a
      stenosis and his abscesses had been treated by surgical drainage. He had been
      taking azathioprine therapy for approximately 5.5 years and had received high
      dose steroids. He had also previously taken metronidazole and antihypertensive
      medications. INVESTIGATIONS: Physical examination, laboratory investigations
      including hemoglobin levels and white blood cell counts, genetic testing, CT,
      bone-marrow biopsy, immunophenotyping by fluorescence-activated cell sorting,
      polymerase chain reaction analyses, fluorescence in situ hybridization, sputum
      culture and diagnostic splenectomy. DIAGNOSIS: Hepatosplenic T-cell lymphoma.
      MANAGEMENT: Splenectomy, antibiotic therapy and chemotherapy with
      cyclophosphamide.

PMID- 19575027
TI  - Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of
      bronchial asthma: the importance of gene-gene and gene-environment interactions
      for disease susceptibility.
AB  - The aim of our pilot study was to evaluate the contribution of genes for
      xenobiotic-metabolizing enzymes (XMEs) for the development of bronchial asthma.
      We have genotyped 25 polymorphic variants of 18 key XME genes in 429 Russians,
      including 215 asthmatics and 214 healthy controls by a polymerase chain reaction,
      followed by restriction fragment length polymorphism analyses. We found for the
      first time significant associations of CYP1B1 V432L (P=0.045), PON1 Q192R
      (P=0.039) and UGT1A6 T181A (P=0.025) gene polymorphisms with asthma
      susceptibility. Significant P-values were evaluated through Monte-Carlo
      simulations. The multifactor-dimensionality reduction method has obtained the
      best three-locus model for gene-gene interactions between three loci, EPHX1
      Y113H, CYP1B1 V432L and CYP2D6 G1934A, in asthma at a maximum cross-validation
      consistency of 100% (P=0.05) and a minimum prediction error of 37.8%. We revealed
      statistically significant gene-environment interactions (XME genotypes-smoking
      interactions) responsible for asthma susceptibility for seven XME genes. A
      specific pattern of gametic correlations between alleles of XME genes was found
      in asthmatics in comparison with healthy individuals. The study results point to
      the potential relevance of toxicogenomic mechanisms of bronchial asthma in the
      modern world, and may thereby provide a novel direction in the genetic research
      of the respiratory disease in the future.

PMID- 19575029
TI  - Lifetime costs and effectiveness of ReSTOR compared with a monofocal IOL and
      Array-SA40 in the Netherlands.
AB  - PURPOSE: To estimate the lifetime cost consequences for society and the National
      Health Service (NHS) of bilateral monofocal (SI40NB) or multifocal (ReSTOR or
      Array-SA40) intraocular lense (IOL) implantation after cataract surgery. SETTING:
      Public hospital in the Netherlands. METHODS: A Markov model simulated three
      cohorts of patients followed 69 until 100 years of age, or death. Spectacle
      independence rates for each IOL were adjusted to the results of a randomized
      clinical trial that compared monofocal and multifocal Array-SA40 IOL implants,
      together with a prospective cohort of patients implanted with ReSTOR. Adjustment
      was performed using the propensity score method in a multivariate analysis.
      Resource consumption was estimated from a dedicated Dutch survey. Dutch unit
      costs were applied to spectacles, cataract surgery, IOLs, visits to
      ophthalmologists, optometrists, transport, and spectacle cleaning materials. Cost
      discounted at 4% and undiscounted economic results were calculated. RESULTS:
      Spectacle independence rates were 86.0% for ReSTOR, 8.7% for monofocal IOLs, and
      8.5% for Array-SA40. Patients lived without needing spectacles for 12.9 years
      after ReSTOR, for 1.4 years after monofocal IOLs, and 1.3 years after Array-SA40.
      ReSTOR patients bought 6.4 fewer pairs of spectacles than monofocal patients.
      Lifetime discounted cost consequences for the society were ReSTOR euro3969,
      monofocal IOLs euro4123, and Array-SA40 euro5326. Corresponding costs for the NHS
      were euro2415, euro2555, and euro2556, respectively. CONCLUSIONS: ReSTOR IOLs
      provided higher levels of spectacle independence than monofocal SI40NB or
      multifocal Array-SA40 IOLs resulting in savings, compared to a monofocal, over
      the period modelled of euro315 for society and euro140 for the NHS.

PMID- 19575031
TI  - Reducing the rate of cataract surgery cancellation due to blepharitis.

PMID- 19575028
TI  - Structure and signalling in the IL-17 receptor family.
AB  - Interleukin-17A (IL-17A), the hallmark cytokine of the newly defined T helper 17
      (T(H)17) cell subset, has important roles in protecting the host against
      extracellular pathogens, but also promotes inflammatory pathology in autoimmune
      disease. IL-17A and its receptor (IL-17RA) are the founding members of a newly
      described family of cytokines and receptors that have unique structural features
      which distinguish them from other cytokine families. Research defining the signal
      transduction pathways induced by IL-17R family cytokines has lagged behind that
      of other cytokine families, but studies in the past 2 years have begun to
      delineate unusual functional motifs and new proximal signalling mediators used by
      the IL-17R family to mediate downstream events.

PMID- 19575032
TI  - Guidance on patient safety in ophthalmology from the Royal College of
      Ophthalmologists.
AB  - OBJECTIVE AND METHOD: Safer care is a strategic priority for healthcare
      organisations. Yet, the detail of how to improve patient safety is complex. To
      this end the Royal College of Ophthalmologists has provided guidance to improve
      ophthalmic patient safety, and is presented in this paper. Which patient safety
      incidents to report and analyze in ophthalmic practice are outlined and how to do
      so is also discussed. The focus and setting of this review is on the current
      organisation of healthcare in United Kingdom and primarily--but not exclusively-
      within the National Health Service (NHS) provision, as relevant to ophthalmology.
      CONCLUSIONS: Efforts for improvement in ophthalmic patient safety and quality of
      care are vital and require professional leadership and engagement. The Royal
      College of Ophthalmologists' role and position in this regard is outlined.

PMID- 19575033
TI  - Regulation of vascular endothelial growth factor and pigment epithelium-derived
      factor in rat retinal explants under retinal acidification.
AB  - PURPOSE: To explore whether retinal acidification independently regulates the
      production of vascular endothelial growth factor (VEGF) and pigment epithelium
      derived factor (PEDF) and whether the regulation is related to oxidative stress.
      METHODS: After culture of rat retinas in the medium with normal pH (7.2) or
      acidic pH (6.8 or 6.5), or followed by pH reversion back to the normal, or
      meanwhile with the presence of antioxidants, VEGF and PEDF mRNA and protein were
      determined by quantitative real-time reverse transcription-ploymerase chain
      reaction and western blot. RESULTS: Retinal acidification significantly increased
      the expression of VEGF and PEDF mRNA and protein. pH reversion recovered VEGF and
      PEDF mRNA and reduced VEGF and PEDF protein induced by acidification.
      Acidification-increased VEGF was completely inhibited in the retinas of pH 6.8,
      and largely reduced in the retinas of pH 6.5 by antioxidants. Antioxidants
      further increased PEDF mRNA and protein induced by retinal acidification.
      CONCLUSIONS: VEGF can be induced by retinal acidification alone, which may be
      regulated through oxidative stress, among other factors. The fact that increased
      PEDF under retinal acidification is promoted by antioxidants suggests that
      oxidative stress inhibits the production of PEDF.

PMID- 19575034
TI  - A structural investigation of corneal graft failure in suspected recurrent
      keratoconus.
AB  - PURPOSE: Penetrating keratoplasty was performed on the right eye of a 51-year-old
      patient diagnosed with advanced bilateral keratoconus. Thirteen years later, an
      8.5 mm regraft was required as a result of gross vascularisation, a poor
      epithelium, and suspected recurrent keratoconus. To learn more about the
      structural basis for graft failure, we examined the removed tissue for the
      presence of abnormalities in the stroma and limiting membranes. METHODS: X-ray
      scattering and electron microscopy were used to study the failed-graft tissue to
      provide information on the integrity of the limiting membranes and the diameter,
      dominant orientation, and distribution of collagen within the corneal stroma. The
      findings were compared with similar structural data from normal and keratoconus
      corneas. RESULTS: In contrast to the keratoconus cornea, a normal orientation and
      distribution of collagen was seen throughout most of the failed-graft tissue,
      although abnormalities were observed in the infero-nasal quadrant at the original
      graft/host junction. The average diameter of collagen fibrils in the failed-graft
      button did not differ from that of normal corneas. CONCLUSIONS: The structural
      abnormalities identified in this case of graft failure were not consistent with
      those typically seen in keratoconus. The clear demarcation of the graft/host
      boundary 13 years after surgery suggests that a normal stromal collagen
      arrangement may never be fully achieved in corneal graft wounds.

PMID- 19575035
TI  - Ocular hypertension and glaucoma in Graves' orbitopathy.

PMID- 19575036
TI  - On light-induced sneezing.
AB  - PURPOSE: To investigate whether the tickling inside the nose before a light
      induced sneeze in susceptible individuals is correlated to a recordable local
      activity or not. METHODS: Seven healthy volunteers, three with a history of light
      induced sneezing, were stimulated with stroboscopic light or a strong halogen
      lamp. Recording was done with an evoked potential averaging technique via
      intranasal electrodes placed in such a way that they substantially reduced the
      strong electrical response from the retina. RESULTS: Despite an adequate light
      stimulus, no reproducible electrical activity could be recorded from any of the
      members in any experiment. CONCLUSION: Light-induced sneezing is presumably a
      central phenomenon. The electrical activity travels through the optic pathways
      straight to the trigeminal nucleus and the tickling is a referred sensation. A
      genetic variation in the distance between the optic pathways (colliculus
      superior) and the mesencephalic part of the trigeminal nucleus may explain why
      light-induced sneezing is more common in certain families and races.

PMID- 19575037
TI  - Ensuring the quality of cataract referrals.

PMID- 19575038
TI  - Five new epothilone metabolites from Sorangium cellulosum strain So0157-2.
AB  - With the aim of identifying more novel natural epothilone derivatives produced by
      the epothilones A and B producing strain Sorangium cellulosum strain So0157-2, a
      large-scale fermentation (5000 l) of the strain was carried out. As a result,
      five new epothilone variants (1-5) were isolated from the fermentation broth.
      Their structures were established as 3-alpha-D-arabinofuranosides of epothilones
      A (1), B (2), D (3), C(9) (4) and 8-demethyl epothilone A (5) by extensive NMR
      analysis and chemical methods. Bioassay results showed that compounds 1 and 2 had
      a weaker cytotoxic activity than did epothilone B.

PMID- 19575039
TI  - Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological
      activity and therapeutic potential.
AB  - Iminosugars, which carry a basic nitrogen in the carbohydrate ring, have
      attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars,
      a new class of iminosugars, have a nitrogen atom in place of the anomeric carbon.
      Various kinds of 1-N-iminosugars have been synthesized from glyconolactones as a
      chiral source in a totally stereospecific manner and/or by the convergent
      strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated
      form of 1-N-iminosugar mimics the charge at the anomeric position in the
      transition state of enzymatic glycosidic hydrolysis, resulting in a strong and
      specific inhibition of glycosidases and glycosyltransferases. They have been
      recently recognized as a new source of therapeutic drug candidates in a wide
      range of diseases associated with the carbohydrate metabolism of glycoconjugates,
      such as tumor metastasis, influenza virus infection, lysosomal storage disorder
      and so forth.

PMID- 19575040
TI  - Two new members of mycophenolic acid family from Penicillium brevicompactum
      Dierckx.

PMID- 19575041
TI  - Solid-phase total synthesis of the chitinase inhibitor Argadin using a supported
      acetal resin.
AB  - A versatile solid-phase total synthesis was applied to the rapid preparation of
      Argadin, a natural product isolated and characterized as a cyclopentapeptide by
      our group, which possesses superior inhibitory activity against family-18
      chitinases. The synthetic strategy includes peptide synthesis by using an Fmoc (9
      fluorenylmethoxycarbonyl) protective group, macrolactamization, acetylguanylation
      and formation of hemiaminal accompanied by total deprotection, including cleavage
      from resin.

PMID- 19575042
TI  - In vitro evaluation of the antimicrobial activity of HM-242, a novel antiseptic
      compound.
AB  - The antimicrobial activities of N(4)-octyl-6,6-dimethyl-N(2)-(4-methylbenzyl)-1,6
      dihydro-1,3,5-triazine-2,4-diamine (HM-242), a novel synthetic compound, were
      compared with those of chlorhexidine gluconate (CHG). HM-242 was a more potent
      microbicide than CHG in vitro; however, its minimal inhibitory concentrations
      were similar. In particular, HM-242 killed various Gram-positive bacteria,
      including methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      Enterococcus faecalis, both efficiently and rapidly. HM-242 also showed potent
      virucidal activity against enveloped viruses such as influenza virus and herpes
      simplex virus. These characteristics suggest that HM-242 may well be useful as an
      antiseptic.

PMID- 19575043
TI  - The first total synthesis of nidulalin A, a dihydroxanthone possessing multiple
      bioactivities.

PMID- 19575044
TI  - Oligomycin induced the proteasomal degradation of cyclin D1 protein.
AB  - We searched for compounds that affect the cyclin D1/retinoblastoma protein
      pathway from the in-house natural product library using a recombinant adenovirus
      with the Cre/loxP-regulated cyclin D1 overexpression system, and we found that
      oligomycin inhibited cell growth more effectively in cyclin D1-overexpressing
      SW480 cells than in control SW480 cells. We also found that oligomycin reduced
      the expression levels of cyclin D1 protein and that this reduction is, at least
      in part, mediated by Thr-286 phosphorylation-dependent proteasomal degradation.

PMID- 19575045
TI  - Antitumoral efficacy of DNA nanoparticles in murine models of lung cancer and
      pulmonary metastasis.
AB  - Polyethylenimine (PEI)-DNA complexes are nanoparticles that are able to
      efficiently transfer plasmids to the lungs. Interleukin-12 (IL12) gene transfer
      using PEI may represent an important strategy for lung cancer treatment. In this
      study, we evaluated the antitumoral efficacy of the administration of PEI-DNA
      nanoparticles carrying IL12 gene (PEI-IL12) for the treatment of lung cancer and
      pulmonary metastases in animal models. After inoculation of tumor cells, mice
      were treated intravenously with a single dose of PEI-IL12, PEI nanoparticles
      carrying the reporter gene beta-galactosidase (PEI-LacZ) or vehicle. Transgene
      expression, survival rates and immune response were analyzed in both models.
      Administration of PEI-LacZ and PEI-IL12 nanoparticles controlled tumor growth and
      prolonged survival times in both animal models. Although PEI-IL12 and PEI-LacZ
      administration showed similar antitumoral effects in the lung cancer model, the
      efficacy of PEI-IL12 was significantly superior in the inhibition of the
      development of pulmonary metastases. Furthermore, the administration of PEI-DNA
      nanoparticles results in the production of high levels of proinflammatory
      cytokines. Our results showed that PEI-DNA nanoparticles are an efficient vector
      for mediating gene transfer to the lungs, are a potent inducer of the innate
      immune response and represents an interesting strategy for the treatment of
      bronchogenic carcinoma and metastatic lung carcinoma.

PMID- 19575048
TI  - A prospective clinical study to evaluate the effect of manual and power
      toothbrushes on pre-existing gingival recessions.
AB  - AIM: To evaluate gingival recession changes after six months of brushing with an
      oscillating-rotating power toothbrush (PT) or an ADA reference manual toothbrush
      (MT). METHODS AND MATERIALS: Healthy subjects with pre-existing recession were
      assigned to brush with either a PT (n=55) or an ADA reference MT (n=54) according
      to a prospective randomized, controlled, single-blind, parallel group design.
      Participants were asked to brush their teeth twice daily for two minutes each
      with the same fluoride toothpaste. Clinical attachment loss and probing pocket
      depths (PPDs) were measured at six sites per tooth to the nearest mm by one
      calibrated examiner at baseline and after six months. Gingival recession was
      calculated as the differences between clinical attachment loss and PPDs overall
      and separately at individual sites. RESULTS: As compared with baseline, overall
      recession at six months was reduced from 2.35 +/- 0.35 mm to 1.98 +/- 0.55 mm
      (p<0.001) in the PT group and from 2.26 +/- 0.31 mm to 1.90 +/- 0.45 mm (p<0.001)
      in the MT group. The data showed 40% (power) and 38% (manual) of all recession
      sites improved by at least 0.5 mm while 51% and 54% remained unchanged. Eight
      percent and 7% recessions increased over time. Differences between groups were
      not statistically significant at either timepoint. CONCLUSION: Both the PT and
      the MT significantly reduced pre-existing gingival recession after six months of
      brushing. This may have been due to improved brushing technique (i.e., Hawthorne
      effect). CLINICAL SIGNIFICANCE: Based on these six-month data, concern that power
      tooth brushing results in a higher risk for gingival recession is not warranted.

PMID- 19575049
TI  - Effect of different conditioning protocols on the adhesion of a glass ionomer
      cement to dentin.
AB  - AIM: The purpose of this study was to assess the effect of different surface
      treatments on the shear bond strength (SBS) of a resin modified glass ionomer
      cement (RMGIC) to dentin. METHODS AND MATERIALS: Forty human third molar teeth
      were randomly divided into four groups (n=10). The occlusal enamel was removed to
      obtain a flat surface of dentin. Each group was treated as follows: Group 1: 10%
      polyacrylic acid (positive control); Group 2: 37% phosphoric acid followed by 5%
      sodium hypochlorite (NaOCl); Group 3: 1.1% APF gel; and Group 4: no conditioning
      (negative control). Fuji II LC glass ionomer was bonded to dentin using a
      cylindrical mold. Samples were thermocycled and debonded using a shear force with
      a crosshead speed of 0.5 mm/min. Data were analyzed using one-way analysis of
      variance (ANOVA) and Tukey tests (a = 0.05). RESULTS: The mean SBS in Groups 1
      through 4 were 11.562+/-3.148, 8.060+/-1.781, 8.830+/-1.554, and 3.074+/-0.784
      (MPa), respectively. There were significant differences in the SBS between Group
      1 with other groups (P<0.05). There were no statistically significant differences
      between Groups 2 and 3, but the SBS of both of them were significantly higher
      than that of Group 4 (P<0.05). CONCLUSION: Although the dentin SBS of Fuji II LC
      after conditioning with APF and phosphoric acid followed by NaOCl was greater
      than the unconditioned group (Group 4), polyacrylic acid yielded the best result.
      CLINICAL SIGNIFICANCE: Proper conditioning of dentin is effective in promoting
      close adaptation of RMGIC to dentin.

PMID- 19575050
TI  - Effects of surface texture and etching time on roughness and bond strength to
      ground enamel.
AB  - AIM: The aim of this study was to assess the influence of surface texture and
      etching technique on surface roughness (Ra) and bond strength (BS) to enamel and
      to determine if a correlation exists between them. METHODS AND MATERIALS: Fifty
      enamel blocks were either roughened with 600-grit SiC paper or polished with
      diamond pastes. After establishing ten test groups (n=5), the initial Ra
      measurements, rough (R) and smooth (S) enamel surfaces were etched according to
      the following protocols: Group 1(R)/Group 2(S)- 35% phosphoric acid gel (H3PO4)
      for 15 seconds; Group 3(R)/Group 4(S)- 35% H3PO4 for 60 seconds; Group 5(R)/Group
      6(S)- Clearfil SE Bond primer for 20 seconds; Group 7(R)/Group 8(S)- self-etching
      primer (SEP) for 60 seconds; Group 9(R)/Group 10(S)- 35% H3PO4 for 15 seconds +
      SEP for 20 seconds. After treatments, a new Ra measurement was performed and
      enamel surfaces were bonded with either Single Bond (Group 1 to Group 4) or
      Clearfil SE Bond (Group 5 to Group 10). Afterwards, specimens were prepared for
      the microtensile test. Ra values were analyzed using repeated-measures analysis
      of variance (ANOVA) and the BS values were analyzed using a two-way ANOVA and
      Tukey test (5%). Correlation between BS and Ra values was assessed using the
      Pearson's test. RESULTS: The application of SEP produced the lowest Ra values. No
      significant difference was detected between the BS values of polished and rough
      surfaces. No correlation was observed between Ra and BS values. Even though
      etching enamel with the SEP resulted in a surface with less roughness, similar BS
      values were observed for both self-etching and etch-and-rinse techniques.
      CONCLUSION: Within the limits of this study increasing the etching time or
      combining both etching techniques failed to improve the BS using SEP or etch-and
      rinse systems. CLINICAL SIGNIFICANCE: Based on the findings of this study, there
      is no clinical justification for increasing the etching time or for combining the
      use of a SEP following the use of a 35% H3PO4 etchant to achieve a greater BS to
      ground enamel.

PMID- 19575051
TI  - Clinical evaluation of polyamide polymer burs for selective carious dentin
      removal.
AB  - AIM: The aim of this study was to evaluate the carious dentin removal efficacy of
      new rotary polyamide burs capable of selectively removing infected dentin without
      removing sound dentin. METHODS AND MATERIALS: This study included 40 subjects
      with bilateral occlusal carious lesions on mandibular first permanent molars. The
      lesions were randomly assigned to receive one restoration after carious dentin
      removal with a polymer bur and the second after removal of carious dentin with a
      carbon steel round bur. Both procedures were completed by a single operator in
      one appointment. The efficacy of caries removal, time taken for caries removal,
      and patients' perception of the treatment were evaluated. The restorations were
      evaluated immediately and after six months using intraoral periapical radiographs
      (IOPA). RESULTS: The results revealed statistically significant differences
      between the polymer burs and carbon steel burs with respect to caries removal
      efficacy (p<0.001) and the time taken for caries removal (p<0.001). No
      statistically significant results were obtained regarding patients' perception of
      the treatment and longevity of the restorations. CONCLUSION: Carbon steel round
      burs remove caries lesions more efficiently than polymer burs but they tend to
      contribute to the over-preparation of the cavity. Polyamide burs were found to be
      self-limiting and lose their cutting efficiency on reaching affected dentin and
      do not cut sound dentin. The time required for caries removal using the polymer
      bur was significantly longer than when using a carbon steel round bur. CLINICAL
      SIGNIFICANCE: One of the goals of conservative dentistry is to develop a method
      for removing caries-infected dentin while preserving caries-unaffected dentin.
      The use of polymer burs appears to offer a straightforward and efficient means
      for achieving this goal and conserving healthy tooth structure.

PMID- 19575052
TI  - Evaluation of bone healing following immediate and delayed dental implant
      placement.
AB  - AIM: The purpose of this study was to compare bone healing and coronal bone
      remodeling following both immediate and delayed placement of titanium dental
      implants in extraction sockets. METHODS AND MATERIALS: The study included 49
      patients (28 women, 21 men) in need of implant treatment in the anterior teeth
      region of either the maxilla or mandible. Twenty-three subjects received 37
      immediate (Im) implants and 26 subjects received 37 delayed (De) implants. The
      implants were placed immediately in the alveoli following the extraction in the
      Im group and the implants in the De group were placed approximately six months
      following the extractions. The width and depth of the marginal bone defects
      mesial and distal to the implants were evaluated radiographically using computer
      software designed to measure distances in digitized radiographs. The mean
      reduction of bone defect over time was 48% (from 3.4 to 1.3 mm) in the Im group
      which was statistically significant (P <0.05) when tested using a sample t-test,
      while the mean reduction was 17% (from 2.1 to 1.9 mm) in the De group.
      CONCLUSION: The potential exists for bone healing and remodeling in fresh
      extraction socket defects associated with immediately placed implants. CLINICAL
      SIGNIFICANCE: Im implantation offers the advantages of reduced operating time and
      the preservation of alveolar bone volume.

PMID- 19575053
TI  - An in vivo evaluation of two types of files used to accurately determine the
      diameter of the apical constriction of a root canal: an in vivo study.
AB  - AIM: The aim of this study was to compare sizes of the first instrument with or
      without a taper that binds at the apical constriction of a root canal after
      coronal flaring. METHODS AND MATERIALS: A total of 310 canals were evaluated in
      patients presenting for root canal therapy. Canals with intact apices were
      selected. After gaining straight line endodontic access, the coronal third was
      flared using Gates-Glidden drills. Working length was determined using an apex
      locator. ISO Standard K-files (tapered) were passively introduced into the canals
      starting with a No. 15 file. The first K-file size to bind against the canal
      walls without pushing and to reach the working length was recorded as the FKFB
      (First K File to Bind). Next, ISO Standard Lightspeed files (non-tapered
      instruments) starting with No. 20 were then gently introduced by hand to each
      canal in ascending order to the working length. The first size of a Lightspeed
      instrument to bind against the canal walls and reach the working length was
      recorded as FLSB (First Light Speed to Bind). In all instances a larger file was
      introduced to ensure it could not reach the same depth (i.e., working length).
      Statistical analysis was carried out using a univariate analysis of variance
      (ANOVA). RESULTS: The average size of the FLSB to bind against the canal walls
      first at the working length was approximately two ISO sizes larger than the FKFB
      (P<0.001). CONCLUSION: The clinician should consider introducing a non-tapered
      instrument to working length after coronal flaring because determination of the
      initial narrow apical canal diameter plays a major factor in identifying the
      extent of final apical shaping. Because the first non-tapered instrument that
      binds the apical constriction is larger than the corresponding tapered
      instrument, it better reflects the actual narrow apical diameter of the canal.
      CLINICAL SIGNIFICANCE: The initiation of canal instrumentation with a K-file size
      three sizes beyond the mean values of the FLSB will result in greater final
      enlargement of the canal compared to starting with the FKFB. This increased canal
      enlargement facilitates improved mechanical and chemical cleansing of the root
      canal ensuring removal of more microorganisms and their substrates, thus,
      improving the outcome of the treatment.

PMID- 19575054
TI  - Dental caries in pre-term and low birth-weight children and related factors.
AB  - AIM: The aims of this study were to determine the prevalence of dental caries in
      three to four-year-old children born pre-term and with a low birth weight (PLBW)
      to be compared with normal birth-weight children (NBW) and further to investigate
      the impact of relative risk factors on the development of dental caries in
      primary teeth. METHODS AND MATERIALS: This cross-sectional case-control study was
      conducted on 90 children (45 PLBW and 45 NBW). The demographic data and
      information about feeding practices was ascertained using a structured
      questionnaire. Dental caries status (dmft) was determined, and the differences
      between the two groups were tested using the Fisher's exact and the Mann-Whitney
      U tests at a confidence level of 5%. RESULTS: Twenty-five children (eight PLBW
      and 17 NBW) were caries free, and the mean+/-SD dmft was 2.5+/-0.3 in PLBW and
      2.2+/-0.4 in NBW children (p>0.05). The length of feeding in PLBW children was
      lower than the NBW group (p>0.05). CONCLUSION: The prevalence of dental caries
      did not differ between the PLBW and NBW children. CLINICAL SIGNIFICANCE: Enamel
      hypoplasia and snacking were not common in PLBW children which may account for
      the lack of difference in dental caries between the two groups.

PMID- 19575055
TI  - Bronchial asthma and dental caries risk: results from a case control study.
AB  - AIM: The present study was conducted with the objective of assessing the dental
      caries status of asthmatic patients in the age group of 11-25 years and to
      examine the possible association of these conditions to various aspects of
      bronchial asthma and its management. METHODS AND MATERIALS: The present study was
      conducted on 80 asthmatic patients receiving treatment at the KMC Hospital,
      Mangalore, India. They were examined for their caries status, and the scores were
      compared with an age, sex, and socioeconomic status matched group of 80 non
      asthmatic patients as controls. The mean age of asthmatics was 17.4 (+/-4.3)
      years and mean duration of asthma was 17.69 (+/-7.66) months. RESULTS: The
      results showed a significantly higher prevalence of caries among asthmatic
      patients as compared to the matched control group as well as a positive
      correlation between the duration of asthma and the caries indices. CONCLUSION:
      There is a need to create awareness among dental practitioners regarding the
      increased caries risk of asthmatic patients. CLINICIAL SIGNIFICANCE: Special
      preventive and educational measures will be required to prevent caries and other
      oral diseases in asthmatic patients.

PMID- 19575056
TI  - Palatal and labially impacted maxillary canine-associated dental anomalies: a
      comparative study.
AB  - AIM: To determine the association of impacted maxillary canines with other
      developmental dental anomalies and compare them with a control population and to
      compare palatally and labially impacted canine associated anomalies. METHODS AND
      MATERIALS: Ninety non-syndromic orthodontic patients from a south Indian
      population, with either labial or palatal impactions of one or both maxillary
      canine teeth, were selected for the study group. A group of 250 patients who had
      normally erupted maxillary canines were selected as controls. Clinical findings
      and panoramic radiographs were used to identify dental anomalies. RESULTS:
      Prevalence of premolar rotation was found to be 80% in the study group followed
      by canine rotation (20%), taurodontism (26.6%), infraocclusion of premolars
      (25.5%), impacted mandibular canine (11.1%), and peg lateral (7.7%). Forty-nine
      (54.4%) palatally impacted, 37 (41.1%) labially impacted, and 4 (4.4%) centrally
      impacted canines were also observed. Of the 250 subjects in the control group
      78.8% presented with premolar rotation. Maxillary canine transmigration,
      infraocclusion of premolars, anomalies of maxillary lateral incisors, and
      taurodontism showed significant associations with palatally impacted canines
      (P<0.05). CONCLUSION: The present study illustrates a significant association of
      anomalous maxillary lateral, anomalous mandibular canine, taurodontism, infra
      occlusion of premolar, over retained deciduous molar, and maxillary canine
      transmigration with ectopically placed canines. These associations suggest these
      conditions may share a common genetic origin and existence of these anomalies can
      anticipate maxillary canine impaction which can help in cautious observation and
      early treatment for maxillary canine impaction. CLINICAL SIGNIFICANCE: Anomalous
      lateral incisors can serve as a predictor for palatal maxillary canine impaction.
      These anomalies could serve as an easily recognized, early warning sign for the
      monitoring of the canine position and timely early referral in appropriate cases.

PMID- 19575057
TI  - Teething problems and parental beliefs in Nigeria.
AB  - AIM: To determine signs and symptoms associated with teething, parental beliefs
      about teething, and the effects of socioeconomic status on teething in Nigerian
      children. METHODS AND MATERIALS: A cross-sectional study consisting of 1,013
      mothers of children between the ages four to 36 months who visited the
      immunization clinics at the Community Health Centres in Ife Central and Ife East
      Local Government Areas. Data was analyzed using STATA (Intercooled release 9) for
      Windows. RESULTS: A total of 765 mothers (75.5%) reported systemic signs and
      symptoms in their children. Fever (51.8%), diarrhea (12.5%), and vomiting (2.9%)
      were the most prevalent symptoms and signs reported. Teething problems were
      reported by 60% of mothers from a high socioeconomic class, as well as 76.7% and
      77.9% from middle and low socioeconomic classes, respectively. Interestingly,
      65.5% of mothers believed teething should be accompanied with systemic signs and
      symptoms such as fever (42.1%), diarrhea (13.9%), and vomiting (0.6%). No
      significant difference was noted between breastfeeding status, gender of the
      child, and reported systemic signs and symptoms noticed by the mothers.
      CONCLUSION: Most mothers in the study reported signs and symptoms adduced to
      teething in their children irrespective of their beliefs. Fever ranked highest of
      the signs and symptoms reported. Mothers of children from the high socioeconomic
      class reported fewer teething symptoms. Breastfeeding status and gender of the
      child had no effect on teething problems in the children studied. CLINICAL
      SIGNIFICANCE: Most signs and symptoms adduced to teething by parents may actually
      be due to underlying infections. Thus, there is a need to rule out occult
      infection during the tooth eruption period.

PMID- 19575058
TI  - A review of the biological and clinical aspects of radiation caries.
AB  - AIM: The aim of this article is to review the clinical and biological features
      underlying the development and progression of radiation caries. BACKGROUND:
      Although radiotherapy (RT) plays an important role in the management of patients
      with head and neck cancer (HNC), it is also associated with several undesired
      side effects such as radiation caries which is a common, yet serious,
      complication. To review the condition, the Pubmed database was searched using the
      keywords "radiotherapy," "radiation," "caries," "hyposalivation," "prevention"
      and "management". Only studies published in the English language were selected.
      Cross-referencing identified additionally relevant studies. REVIEW RESULTS: RT
      leads to alterations in the dentition, saliva, oral microflora, and diet of
      patients. Consequently, irradiated patients are at increased risk for the
      development of a rapid, rampant carious process known as radiation caries.
      Motivation of patients, adequate plaque control, stimulation of salivary flow,
      fluoride use, and nutritional orientation are essential to reduce the incidence
      of radiation caries and ultimately improve the quality of life for HNC patients.
      CONCLUSION: Radiation caries is an aggressive side effect of RT. Dentists play an
      important role in the prevention of the condition via comprehensive oral
      healthcare before, during, and after the active cancer therapy. CLINICAL
      SIGNIFICANCE: Dentists should understand the clinical and biological aspects
      underlying radiation caries to prevent the development of lesions and provide
      optimal treatment when needed.

PMID- 19575059
TI  - Stem cells: therapeutic potential in dentistry.
AB  - AIM: The aim of this paper is to present a review and discussion of the current
      status of stem cell research with regard to tooth generation. BACKGROUND: Stem
      cells have been isolated from the pulp tissue of both deciduous and permanent
      teeth as well as from the periodontal ligament. Dental pulp stem cells
      demonstrate the capacity to form a dentin pulp-like complex in immunocompromised
      mice. A tooth-like structure was successfully formed, using a heterogeneous
      mixture of dental enamel epithelium, pulp mesenchymal cells, and scaffolds.
      CONCLUSION: The scientific community understands the need for more investigations
      to completely understand the conditions that would best favor the creation of a
      tooth substitute. Recent gains in the understanding of the molecular regulation
      of tooth morphogenesis, stem cell biology, and biotechnology offers the
      opportunity to realize this goal. CLINICAL SIGNIFICANCE: These findings, combined
      with the recent progress in stem cell research and tissue engineering, might
      allow the development of alternatives for current materials and therapies used to
      treat tooth tissue loss (e.g., enamel, dentin, pulp), reconstruct dentoalveolar
      and craniofacial bone defects, and eventually replace an entire tooth.

PMID- 19575060
TI  - Smoking cessation practices in the dental profession.
AB  - AIM: The purpose of this review is to describe the current status of smoking
      cessation initiatives in the dental profession. REVIEW: A review of the
      initiatives undertaken by the dental profession to adopt smoking cessation
      recommendations as standard of care is presented. SUMMARY: Facts about the
      effects of smoking on the major oral diseases are stated and supported by
      national statistics. The barriers for compliance by dental professionals are
      described based on published research, but even more importantly, possible
      solutions are offered. CLINICAL SIGNIFICANCE: Awareness of the harmful effects of
      smoking tobacco can help dental professionals become more motivated to comply
      with current recommendations for smoking cessation in order to improve the oral
      and general health of the public.

PMID- 19575061
TI  - Fiber-reinforced onlay composite resin restoration: a case report.
AB  - AIM: The purpose of this case report is to describe the clinical procedure for
      fabricating fiber-reinforced composite (FRC) onlay composite resin restorations
      using a FRC as the substructure. BACKGROUND: A variety of therapeutic modalities
      are available to restore teeth with moderate coronal defects in the posterior
      region of the mouth. For patients who refuse complete crown restorations or when
      minimal tooth reduction is preferred, a FRC restoration can be a good alternative
      to conventional restorative techniques. CASE REPORT: A 42-year-old female patient
      presented with an endodontically treated mandibular right first molar with
      extensive destruction of the coronal tooth structure. To conserve the remaining
      tooth structure a FRC resin core substructure was fabricated and veneered with
      Ceramage dentin and enamel hybrid composite to create the final restoration.
      SUMMARY: FRC restorations using adhesive technology appears to be a promising
      restorative option. However, further clinical investigation will be required to
      provide additional information on this technique. Based on the clinical and
      radiographic findings in the present case, the fabrication of a conventional
      crown was avoided in order to conserve the remaining tooth structure. CLINICAL
      SIGNIFICANCE: The restoration of badly damaged teeth is a challenge for
      clinicians when cast crown restorations are not an option for the patient. The
      use of FRC restorations along with adhesive technology may be a rational
      restorative alternative in the near future.

PMID- 19575062
TI  - The complexities of our outer layer.
AB  - Abnormalities of the skin should be easy to manage... it is all laid out in front
      of us to observe, measure, touch, diagnose and treat. Cynics may say that most
      skin problems get better with time, topical corticosteroids and/or topical
      antifungal cream. The surgically minded may say... 'if in doubt, cut it out'.
      Preventive health messages remind us to 'slip, slop and slap' to avoid the
      dangers of harmful ultraviolet (UV) radiation. But it is not always that simple.

PMID- 19575063
TI  - The doctor of the future.
AB  - An invitation to discuss the role of the doctor begs the question, 'What is wrong
      with the status quo?' Given the guild nature of the medical profession, any
      reform will need to be well substantiated.

PMID- 19575064
TI  - Presentations of rash.
AB  - The gender distribution of patients presenting with rash were similar to all
      BEACH encounters. However, younger patients were more likely to present with
      rash, with one-quarter (24.5%) of patients being under the age of 15 years
      compared with 11.8% of all encounters.

PMID- 19575065
TI  - Cutaneous melanoma--atypical variants and presentations.
AB  - BACKGROUND: The incidence of melanoma continues to rise in Australia. General
      practitioners treat the majority of skin cancers affecting Australians. In the
      past decade, there has been improved uptake of dermoscopy by GPs who realise its
      value in the assessment of pigmented and nonpigmented lesions. OBJECTIVE: This
      article outlines those variants or presentations of melanoma that create
      diagnostic difficulty for all clinicians. Practice tips regarding clinical
      features or useful dermoscopic clues are included. DISCUSSION: A clinical
      overview of lentigo maligna, acral lentiginous and subungual melanoma, nodular
      melanoma, desmoplastic melanoma, verrucous melanoma and hypomelanotic melanoma is
      presented. Dermoscopy has become a vital diagnostic aid in the assessment of all
      skin lesions. Its value in the diagnosis of melanoma is highlighted where
      relevant. Expert dermatopathology assessment is equally as crucial in reaching a
      correct diagnosis, especially for some of these atypical variants.

PMID- 19575066
TI  - Blistering skin conditions.
AB  - BACKGROUND: Blistering of the skin can be due to a number of diverse aetiologies.
      Pattern and distribution of blisters can be helpful in diagnosis but usually
      biopsy is required for histopathology and immunofluoresence to make an accurate
      diagnosis. OBJECTIVE: This article outlines the clinical and pathological
      features of blistering skin conditions with a particular focus on bullous
      impetigo, dermatitis herpetiformis, bullous pemphigoid and porphyria cutanea
      tarda. DISCUSSION: Infections, contact reactions and drug eruptions should always
      be considered. Occasionally blistering may represent a cutaneous manifestation of
      a metabolic disease such as porphyria. Although rare, it is important to be aware
      of the autoimmune group of blistering diseases, as if unrecognised and untreated,
      they can lead to significant morbidity and mortality. Early referral to a
      dermatologist is important as management of blistering skin conditions can be
      challenging.

PMID- 19575067
TI  - Difficult to diagnose skin cancer--the 'aggressive' BCC.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) are common, and are regularly diagnosed
      and managed by Australian general practitioners. OBJECTIVE: This article
      summarises the types, clinical features, treatment and follow up of BCCs. Two
      cases histories are also presented that highlight the difficulties with
      diagnosing and treating aggressive BCC. DISCUSSION: Aggressive BCCs can invade
      widely before exhibiting obvious clinical signs. Suspicious skin lesions should
      have an adequate biopsy taken to guide management options. Complete BCC excision
      is usually the best treatment, but particular care should be taken when treating
      lesions on cosmetically or functionally sensitive areas. Recurrent disease can
      also be difficult and disfiguring to treat. Specialist involvement will be needed
      for the management of some BCCs. Basal cell carcinomas can recur years after
      treatment. Regular skin checks are important for high risk patients.

PMID- 19575068
TI  - Skin manifestations of systemic disease.
AB  - BACKGROUND: Dermatologic complaints are a common reason for presentation to a
      general practitioner. In some cases, one needs to determine if the complaint may
      be a manifestation of a more serious underlying systemic disease. OBJECTIVE: This
      article aims to highlight common dermatologic presentations where further
      assessment is needed to exclude an underlying systemic disease, to discuss
      classic cutaneous features of specific systemic diseases, and to outline rare
      cutaneous paraneoplastic syndromes. DISCUSSION: Skin manifestations of systemic
      disease are wide, varied, specific and nonspecific. Generalised pruritus and
      cutaneous vasculitis are more common cutaneous presentations where an underlying
      systemic disease may be present and will influence management. In certain chronic
      diseases such as connective tissue disease and chronic liver disease, there are
      characteristic cutaneous findings. Internal malignancies such as multiple myeloma
      may present with distinctive cutaneous findings, which need to be recognised to
      institute a search for the underlying neoplasm. The skin has the potential to
      provide a window into the patient and aid in the diagnosis of diseases of all
      organ systems.

PMID- 19575069
TI  - Weight loss and malnutrition in the elderly--the shared role of GPs and APDs.
AB  - This article forms part of a series looking at the relationship between diet and
      good health, and the role of the dietician in the primary health care team. This
      review highlights some of the physical, social and medical factors that can
      indicate compromised nutritional status in the elderly, the screening tools
      available to detect malnutrition, and when to involve a dietician.

PMID- 19575070
TI  - The role of breast MRI in clinical practice.
AB  - BACKGROUND: The use of magnetic resonance imaging (MRI) for breast screening is
      increasing. Women may approach their general practitioner for advice on its role
      in breast screening and diagnosis. OBJECTIVE: This article provides an evidence
      based update on the role of breast MRI. DISCUSSION: There is good evidence to
      support the use of MRI for cancer screening in younger women at high genetic risk
      of breast cancer. Its use for assessing the extent of disease in the breast after
      breast cancer is diagnosed (local staging) is controversial. Certainly MRI is
      more sensitive than conventional imaging for detecting multifocal/ multicentric
      disease, however, there is evidence that some women have more extensive surgery
      as a result of MRI without clear evidence of benefit. There is no role for MRI as
      a substitute for mammography or for screening women at average risk of breast
      cancer. It also has no routine role as a diagnostic test in women with symptoms.

PMID- 19575071
TI  - Osteomyelitis--a case report.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) infection has
      classically been associated with institutional health care settings such as
      hospitals and nursing homes. OBJECTIVE: This article presents a case of community
      acquired MRSA infection resulting in severe osteomyelitis of the humerus,
      followed by a brief discussion and literature review. DISCUSSION: Over the past
      few years, more community acquired cases of MRSA have occurred. Methicillin
      resistant S. aureus usually infects skin and soft tissue. Occasionally, a life
      threatening infection occurs involving the blood, lungs, heart and bone.

PMID- 19575072
TI  - Harassment of GPs.
AB  - The maintenance of clear professional boundaries is an essential part of general
      practice. Boundary violations are usually considered to be the result of the
      exploitation of a patient by their doctor, but they can also occur as a result of
      the behaviour of a patient. This article discusses harassment and stalking of
      doctors by patients, and outlines some strategies on how to manage this
      situation.

PMID- 19575073
TI  - Electronic medical records--where to from here?
AB  - Ninety percent of general practitioners use computers. Computers are being used
      by GPs for an increasingly broad range of functions. Effectively, Australia now
      has a national electronic medical record (EMR) based in general practice. The
      true benefits of having an EMR will only be realised when we move beyond the idea
      that it is simply information that was once recorded on paper. Electronic medical
      records allow multiple sources of information to come into play in the
      consultation. This article looks at the future of the EMR in general practice and
      how we can use it to improve patient care.

PMID- 19575074
TI  - Bacterial skin infections--an observational study.
AB  - BACKGROUND: We aimed to determine the feasibility of measuring resolution rates
      of bacterial skin infections in general practice. METHODS: Fifteen general
      practitioners recruited patients from March 2005 to October 2007 and collected
      clinical and sociodemographic data at baseline. Patients were followed up at 2
      and 6 weeks to assess lesion resolution. RESULTS: Of 93 recruited participants,
      60 (65%) were followed up at 2 and 6 weeks: 50% (30) had boils, 37% (22) had
      impetigo, 83% (50) were prescribed antibiotics, and active follow up was
      suggested for 47% (28). Thirty percent (18) and 15% (9) of participants had
      nonhealed lesions at 2 and 6 weeks respectively. No associations between
      nonhealing and any modifiable factors investigated were identified. However,
      indigenous patients were more likely to have nonhealed lesions at 2 weeks and new
      lesions at 6 weeks. DISCUSSION: Clinicians need to be aware that nonhealing is
      not infrequent, particularly in indigenous people.

PMID- 19575075
TI  - Anxiety and depression in Chinese patients attending an Australian GP clinic.
AB  - BACKGROUND: Incidence of depression among Chinese people living in traditional
      Asian regions is low. Recent Chinese immigrants to Australia may be at greater
      risk of depression and anxiety because of issues related to integration into
      Australian society. General practitioners are often the first point of contact
      for people with anxiety and depression. Patients from a Chinese background may be
      reluctant to discuss their mental health problems with their GP. METHODS: A cross
      sectional survey was undertaken of Chinese patients 18 years of age and over
      attending a general practice in southwestern Sydney (New South Wales) during July
      2005. Patients were asked to complete the Kessler Psychological Distress Scale
      (K10) and Somatic and Psychological Health Report (SPHERE) depression screening
      questionnaires, along with a demographic questionnaire. All questionnaires were
      available in English or Chinese. RESULTS: A total of 161 patients completed the
      questionnaires. Fifty-five percent (83) of patients had a K10 score that
      indicated medium or high risk, and 44% (71) had a high SPHERE score (PSYCH-6
      and/or SOMA-6). There was an association between increased risk of depression or
      anxiety and reduced occupational status but not social isolation. DISCUSSION:
      Half the Chinese patients presenting at this general practice were at high risk
      of psychological distress (as measured by standard screening instruments). The
      proportion of patients in this study at risk of psychological distress on
      screening is more than would be expected in the general Australian population.
      Though limited by a small sample size and a single general practice location,
      these findings are of concern and should direct further research.

PMID- 19575076
TI  - Education in skin cancer management--assessing knowledge and safety.
AB  - BACKGROUND: General practitioners manage the majority of skin cancers in
      Australia. There are a range of training opportunities for, and certifications
      in, skin cancer management. METHOD: Between 15 June and 25 June 2008, an online
      examination was placed on the Australasian College of Skin Cancer Medicine
      website. Two hundred and forty-five college affiliated doctors were invited by
      email to complete the examination. Thirty questions were asked pertaining to the
      management of a hypothetical case study including melanoma, basal cell carcinoma
      and squamous cell carcinoma. RESULTS: Of 187 doctors who had an active responding
      email address, 140 (75%) took the examination. From a possible score of 100, the
      mean score was 84 +/- 16. The median score was 80. DISCUSSION: Some trends
      emerged. Longer and more detailed training programs correlated with better
      subsequent knowledge retention and safety. Two days of training may not make
      doctors sufficiently safe in skin cancer management; it appeared to improved
      knowledge, but not to a point where unsafe practice was eliminated.

PMID- 19575077
TI  - Discovery of the function of the heart and circulation of blood.

PMID- 19575078
TI  - Cardiovascular effects of Ekebergia capensis Sparrm (Meliaceae) ethanolic leaf
      extract in experimental animal paradigms.
AB  - The purpose of this study was to examine the in vivo effects of Ekebergia
      capensis leaf ethanolic extract (EKE) on the blood pressure of anaesthetised
      normotensive male Wistar rats and conscious weanling Dahl salt-sensitive (DSS)
      rats, which develop hypertension as they age. To investigate possible
      mechanism(s) of the extract's hypotensive effects, the contractile or relaxant
      responses to EKE in the absence or presence of reference drugs were evaluated in
      Wistar rat isolated aortic rings precontracted with methoxamine hydrochloride
      (ME, 10 microM). Acute intravenous administration of EKE elicited hypotensive
      responses in anaesthetised animals, while sub-chronic treatment with the extract
      averted the development of high blood pressure in weanling DSS rats. Isometric
      recordings of methoxamine hydrochloride (ME) pre-contracted, isolated,
      endothelium-intact and -denuded aortic rings revealed concentration-dependent
      relaxation responses to EKE (1-160 mg/ml). The potency was significantly less in
      the endothelium- denuded rings. Inhibitors of endothelium-derived relaxing factor
      (EDRF), L-NAME, methylene blue and indomethacin significantly reduced EKE-evoked
      vasorelaxations in endothelium-intact aortic rings. These results indicate that
      the vasorelaxant effect of EKE was in part mediated via EDRF-dependent or 
      independent pathways. These observations suggest that the hypotensive effect of
      EKE was in part mediated via modulation of total peripheral resistance of the
      vascular smooth muscles.

PMID- 19575079
TI  - Influence of albumin concentration in priming solution on blood viscosity under
      hypothermic conditions.
AB  - OBJECTIVE: Albumin is used routinely as a plasma volume expander in
      cardiopulmonary bypass operations. The effect of two different concentrations of
      albumin in Ringer's lactate on blood viscosity was explored in this study.
      METHODS: Ten healthy volunteers (all male) were included in the study, based on
      their haematocrit levels (42.6 +/- 0.96). Using a heparinised 50-ml syringe, 40
      cm(3) of blood were drawn from the antecubital veins of fasting volunteers. Six
      ml of blood were haemodiluted with 2 ml of albumin (20%), 2 ml of Ringer's
      lactate containing albumin (1.3%), and 2 ml of Ringer's lactate, in order to
      simulate cardiopulmonary bypass conditions. Test tubes with the solutions were
      placed in a 15 degrees C water bath for 25 minutes. Viscosity was measured in the
      haemodiluted blood samples using an Ostwald viscometer. Relative viscosities of
      samples were assessed with SPSS software and the ANOVA test. RESULTS: The mean
      relative viscosity of Ringer's lactate was 4.19 (+/- 0.49), that of Ringer's
      lactate with 1.3% albumin was 4.30 (+/- 0.31), and of 20% albumin was 7.32 (+/-
      0.71). The relative viscosity of Ringer's lactate and Ringer's lactate with 1.3%
      albumin were statistically similar, but that of 20% albumin was higher than the
      Ringer's lactate and Ringer's lactate with 1.3% albumin. CONCLUSION: Albumin is
      used as a plasma volume expander in priming solutions for cardiopulmonary bypass
      operations, but its effect on blood viscosity depends on the concentration of
      albumin used.

PMID- 19575080
TI  - The influence of diabetes on short-term outcome following a prosthetic above-the
      knee femoro-popliteal bypass.
AB  - OBJECTIVES: To assess the influence of diabetes mellitus on early morbidity and
      mortality following a femoro-popliteal bypass. METHODS: Clinical data on patients
      subjected to a prosthetic above-the-knee femoro-popliteal bypass for
      atherothrombotic disease over a four-year period in the Durban Metropolitan
      Vascular Service were culled from a prospectively maintained computerised
      database. The patients were divided into two groups, diabetic and non-diabetic.
      RESULTS: Two hundred and seventeen patient records were analysed; 102 (47%)
      patients were diabetic and 115 (53%) non-diabetic. The mean age in the two groups
      was almost similar. Differences noted between the two groups were that there was
      a higher prevalence of males and cigarette smokers in the non-diabetic group and
      hypertension among the diabetics. The prevalence of ischaemic heart disease in
      the two groups was not statistically significant. The majority of patients in
      both groups presented with critical limb ischaemia. Overall, 208 (96%) of the
      patients had their procedures performed using loco regional anaesthesia. The
      incidence of superficial wound infection between the two groups was not
      statistically significant. Deep infection, which necessitated removal of the
      graft, and cardiovascular complications were significantly higher in the
      diabetics. Four patients (3.9%) in the diabetic group and only one (0.9%) in the
      non-diabetic group died. CONCLUSION: Diabetes mellitus significantly increases
      the incidence of graft sepsis and cardiovascular morbidity in patients undergoing
      above-the-knee femoro-popliteal bypass.

PMID- 19575081
TI  - Relationship between left ventricular diastolic function and geometric patterns
      in Nigerians with newly diagnosed systemic hypertension.
AB  - BACKGROUND: It is not known whether abnormalities of left ventricular diastolic
      function are influenced by the various cardiac geometric patterns in Nigerians
      with newly diagnosed systemic hypertension. OBJECTIVE: To evaluate the
      relationship between the parameters of left ventricular diastolic function and
      the geometric patterns in this group of patients. METHODS: Two-dimensional,
      guided M-mode echocardiography including Doppler was performed in 150
      consecutive, newly diagnosed hypertensive individuals and normotensive controls
      aged between 35 and 74 years. Left ventricular mass index and relative wall
      thickness were used to classify the hypertensive individuals into four geometric
      patterns, and the pulsed-wave Doppler parameters obtained were used to categorise
      the abnormalities of diastolic function. RESULTS: Four left ventricular geometric
      patterns were identified: 23 (15.3%) had normal left ventricle geometry, 33 (22%)
      had concentric remodelling, 37 (24.7%) were found to have eccentric hypertrophy,
      and concentric hypertrophy occurred in 57 (38%) of the hypertensive individuals.
      Left ventricular diastolic dysfunction occurred more in hypertensives with
      concentric left ventricular geometric pattern. Increased left ventricular mass
      index and relative wall thickness were found to be associated with the mitral E
      wave, E/A ratio and pulmonary venous flow S-wave in the hypertensives (p <
      0.001). CONCLUSION: In newly diagnosed Nigerian hypertensives, the abnormalities
      in left ventricular diastolic function varied between the different left
      ventricular geometric patterns, being worst in those with concentric geometry.

PMID- 19575082
TI  - Gender differences in metabolic risk factor prevalence in a South African student
      population.
AB  - We determined selected risk factors for the metabolic syndrome and assessed the
      metabolic risk status (using IDF criteria) of third-year physiology students at
      Stellenbosch University (88 males and 178 females). Outcome measures included
      anthropometry [body mass index (BMI), waist circumference, waist-to-hip ratio],
      blood pressure (BP), resting pulse rate, and fasting blood glucose, total
      cholesterol and triglyceride levels. In addition, students completed a lifestyle
      questionnaire. A number of gender-based differences were found, with male
      students displaying a greater incidence of risk factors for the metabolic
      syndrome: 6% of males versus 3% of females displayed a cluster of three risk
      factors. Twenty-five per cent of female students (but only 14% of males)
      exhibited waist circumferences above the accepted range, which was positively
      correlated, for males and females, with both systolic and diastolic BP, and in
      females only, also with total cholesterol levels. Male students on average
      exercised more than their female counterparts, but also exhibited poorer eating
      habits. Average blood triglyceride levels for both male and female students
      exceeded the accepted threshold (1.85 +/- 1.62 mmol/l and 2.15 +/- 1.79 mmol/l,
      respectively). We concluded that metabolic risk factors were evident in a much
      younger population than commonly expected. Moreover, the gender-specific
      differences observed may impact on future risk assessment and preventative
      measures adopted.

PMID- 19575083
TI  - Echocardiographic assessment of left atrial size in patients with end-stage renal
      disease.
AB  - BACKGROUND: Cardiac disease is the most common cause of death in patients with
      end-stage renal disease. It is assumed that the high rate of cardiovascular
      mortality is related to accelerated atherosclerosis. Patients with chronic renal
      insufficiency have an increased prevalence of coronary artery disease, silent
      myocardial ischaemia, complex ventricular arrhythmias, atrial fibrillation, left
      ventricular hypertrophy, annular mitral and aortic valve calcification, and
      enlargement of the left atrium, than patients with normal renal function. It is
      also well known that haemodialysis is associated with cardiovascular structural
      changes and rapid fluctuations in electrolyte levels. In this study, we sought to
      estimate left atrial size by means of echocardiography and to determine any
      correlations between different echocardiographic measurements in patients with
      end-stage renal disease. METHODS: We analysed data from 123 patients who were on
      regular haemodialysis, by means of traditional transthoracic echocardiographic
      examination. The usual statistical parameters, correlations and the Student's t
      test were performed, with levels of significance of p < 0.01 and p < 0.05.
      RESULTS: The most presented age group was 60 to 69 years old, with a
      predomination of females (56.1%). We found dilated left atrium in 26.02% of the
      study patients and a high statistical correlation between different methods of
      measurement and calculated volumes of the left atrium. CONCLUSION: Evaluation of
      left atrial size should be determined by several different measurements, and left
      atrial enlargement should be seen as a risk factor for advancing disease.

PMID- 19575085
TI  - CT angiography outperforms stress testing in diagnosing coronary artery disease.

PMID- 19575084
TI  - Investigation of predictors of increased creatine kinase levels following
      vascular surgery and the association with peri-operative statin therapy.
AB  - Although peri-operative statin administration is likely to be cardioprotective,
      there remains a concern about the risk of rhabdomyolysis and associated renal
      failure following statin administration in the peri-operative period. The aim of
      this study was to determine independent predictors of creatine kinase (CK)
      elevation following vascular surgery. DESIGN: A retrospective cohort study was
      conducted. A multivariate analysis using binary logistic regression was conducted
      of clinical, surgical and laboratory factors which may be associated with a CK
      exceeding five times the upper limit of normal (ULN). RESULTS: Four independent
      predictors associated with a CK > 5 ULN were identified. Statin therapy was
      protective [odds ratio (OR) 0.096, 95% confidence interval (CI) 0.014-0.68, p =
      0.019], and a serum creatinine > 180 micromol*l(-1), positive serum troponins and
      embolectomy and/or fasciotomy were associated with CK elevation (OR 3.32, 95% CI:
      1.03-10.7, p = 0.04; OR 5.84, 95% CI: 1.52-22.4, p = 0.01; OR 5.62, 95% CI: 1.14
      27.8, p = 0.03 respectively). Statin therapy was associated with decreased
      mortality (OR 0.26, 95% CI: 0.08-0.86, p = 0.028). CONCLUSION: It may be
      preferable to continue statin therapy in vascular surgical patients even when CK
      is elevated, as this may decrease mortality if the CK elevation is in the
      presence of pre-existing renal dysfunction, peri-operative cardiac events or
      following embolectomy or fasciotomy. Further investigation is required to confirm
      this observation.

PMID- 19575086
TI  - Unruptured congenital aneurysm of the sinus of Valsalva in an African population:
      a six-year experience at an echocardiography laboratory.
AB  - Sinus of Valsalva aneurysms (SVA) are considered rare congenital anomalies. Apart
      from a few reported cases of SVA in African patients, there is little information
      on the clinical presentation of this entity in Africans. We describe the clinical
      and echocardiographic features of four consecutive African patients in whom the
      diagnosis of SVA was established over the last six years at the echocardiography
      laboratory of our institution. In this report we compare the clinical and
      echocardiographic features in our patients with those of others published in the
      literature.

PMID- 19575087
TI  - Successful surgical treatment of a rupture to an arteriovenous fistula aneurysm.
AB  - We describe here the successful surgical treatment of a rupture of an
      arteriovenous fistula (AVF) aneurysm that compromised access for dialysis. A 59
      year-old woman had a history of uraemia s/p with an AVF involving the brachial
      artery and basilic vein that had been superficialised for eight years. A sudden
      onset rupture of the aneurysm was diagnosed just after haemodialysis at a local
      specialist clinic. The patient volunteered to receive emergency surgery. Partial
      resection of the aneurysm and anastomosis with 4-0 prolene was performed. She was
      well with regular haemodialysis at the six-month follow-up.

PMID- 19575088
TI  - Cardiac magnetic resonance predicts reversibility of cocaine-induced ventricular
      dysfunction.
AB  - A 30-year-old Caucasian female was admitted with severe biventricular congestive
      heart failure secondary to cocaineinduced cardiomyopathy. Contrast-enhanced
      cardiac magnetic resonance did not reveal myocardial oedema or focal fibrosis.
      The systolic ventricular function recovered fully after 10 weeks of abstinence
      from cocaine and supportive medical treatment. This case report is the first to
      describe findings with magnetic resonance for this condition, and briefly
      discusses its potential value in the evaluation of patients with cocaine-induced
      heart failure.

PMID- 19575089
TI  - Rheumatic valvular heart disease in thalassaemic patients: a summary of reported
      Thai cases.
AB  - Thalassaemia is a serious inherited disorder with a high prevalence in south-east
      Asian countries, including Thailand. Several complications of thalassaemia have
      been documented. Infection is a major problem and the leading cause of death,
      particularly in E-beta thalassaemia.

PMID- 19575090
TI  - The hyperparathyroid heart mimicking acute myocardial infarction.
AB  - Left ventricular hypertrophy is a common complication of primary
      hyperparathyroidism. Numerous disturbances of myocardial physiology have been
      described as a result of excess parathyroid hormone action. In this brief
      communication, another phenotype of the hyperparathyroid heart is proposed, the
      'pseudo-myocardial infarction hyperparathyroid heart'.

PMID- 19575091
TI  - Transoesophageal echocardiography prior to atrial flutter ablation averts a
      dramatic complication.
AB  - Catheter ablation is now the primary strategy for typical atrial flutter, given
      success rates in the order of 95 to 98%, with a low risk of recurrence. It also
      has a low complication rate but is not entirely risk free, and should still be
      approached judiciously as is illustrated by the index case.

PMID- 19575092
TI  - Lower aspirin doses in dual antiplatelet therapy optimise efficacy and safety:
      CHARISMA follow-up study.

PMID- 19575093
TI  - Consistency of treatment effect of perindopril and indapamide across broad
      spectrum of vascular disease.

PMID- 19575094
TI  - Statins reduce stroke risk by one-fifth.

PMID- 19575095
TI  - Clopidogrel/aspirin combination therapy in high-risk atrial fibrillation
      patients.

PMID- 19575096
TI  - JUPITER study highlights value of anti-inflammatory action of rosuvastatin.

PMID- 19575097
TI  - Mother of the nation honoured.

PMID- 19575099
TI  - HPV detection in the oral and genital mucosa of women with positive
      histopathological exam for genital HPV, by means of the PCR.
AB  - Infection by the Human Papilloma Virus (HPV) is one of the most frequent sexually
      transmitted diseases all over the world. The relationship between oral and
      genital HPV remains uncertain, as it is with its role on oral carcinogenesis. The
      goal of the present investigation was to check for the presence of HPV DNA in the
      oral and genital mucosas of women with HPV genital infection, using the
      polymerase chain reaction (PCR). STUDY METHOD: Cross-sectional cohort. MATERIALS
      AND METHODS: This is a pilot and prospective study involving 30 women, aged
      between 14 and 51 years, with HPV genital infection, confirmed by histopathology.
      All the patients were submitted to the exam and sample collection by swabbing the
      oral and genital mucosas in order to test for HPV DNA through the PCR technique.
      RESULTS: None of the oral cavity samples were positive for HPV, while in the
      genital tract, HPV was detected in 17 (57%) of the 30 patients, especially HPVs
      6b and 16. CONCLUSION: Results show a higher percentage of genital HPV in
      comparison to the oral cavity, and suggest that genital HPV does not seem to be a
      predisposing factor for the oral infection in the same patient.

PMID- 19575100
TI  - A critical analysis of 33 patients with substernal goiter surgically treated by
      neck incision.
AB  - The possibility of needing a combined access, with neck and chest incisions makes
      the treatment of substernal goiter a challenge both in the pre-op and the
      intraoperative. We hereby, discuss a standardization of the surgical technique to
      minimize the need for a chest approach, making the substernal goiter a surgically
      treatable disease, through a single neck incision, and with low indices of
      complication. AIM: To assess the substernal goiter surgically approach through a
      neck incision and to analyze the surgical complications. MATERIALS AND METHODS:
      We carried out a historical cohort by retrospective analysis of the charts of
      patients submitted to thyroidectomy, and 33 of them (10.4%) had substernal
      goiter. RESULTS: All 33 patients were surgically treated through a neck incision
      without the need for sternotomy. We did not observe definitive lesions in the
      inferior laryngeal nerve or definitive hypoparathyroidism. Only 2 patients had
      recurrent nerve paresis; and 2 patients were re-operated because of a neck
      hematoma. CONCLUSION: Patients with substernal goiter can be safely treated
      surgically through a single neck incision, bearing low complication rates.

PMID- 19575101
TI  - Alterations in early auditory evoked potentials in multiple sclerosis patients.
AB  - Alterations in early auditory evoked potentials (EAEP) in individuals with
      demyelinating disease are suggestive of lesions in the brainstem. AIM: this study
      aims to evaluate the prevalence of hearing disorders and altered EAEP in multiple
      sclerosis (MS) patients. MATERIALS AND METHOD: sixteen female and nine male
      patients with a defined diagnosis of multiple sclerosis took part in this study.
      All individuals underwent hearing and EAEP tests. The wave forms were categorized
      according to Jerger (1986). RESULTS: fifty EAEP tests were carried out; 70% were
      classified as type I (normal response) according to Jerger's criteria. Altered
      EAEP results in at least one ear were classified into types II, III, IV or V
      according to Jerger. Females accounted for 31.25% of alterations, and males
      44.44%, adding up to 36% of all cases. CONCLUSIONS: these findings stress the
      importance of looking at EAEP in cases where there is suspicion of demyelinating
      disease and in patients with a defined diagnosis for MS.

PMID- 19575102
TI  - Computerized manometry use to evaluate spasm in pharyngoesophageal segment in
      patients with poor tracheoesophageal speech before and after treatment with
      botulinum toxin.
AB  - Tracheoesophageal voice (TEV) with voice prosthesis (VP) is an efficient and
      reproducible method used in vocal rehabilitation after total laryngectomy (TL),
      prevented by spasms in the pharyngoesophageal segment (PES). Computerized
      Manometry (CM) is a new, direct and objective method used to assess the PES. AIM:
      to carry out an objective analysis of the PES, with CM, before and after the
      injection of botulinum toxin (BT). STUDY DESIGN: Clinical-prospective. MATERIALS
      AND METHODS: Analysis of eight patients consecutively submitted to TL with TEV
      and VP, without vocal emission, with PES spasms seen through videofluoroscopy,
      considered the gold standard for spasm detection. All had their spasms treated
      with the injection of 100 units of BT in the PES. The assessment was based on PES
      videofluoroscopy and CM, before and after BT injection. RESULTS: There was a PES
      pressure reduction according to the CM after BT injection in all patients. The
      average pressure in the PES seen through the CM in eight patients before BT
      injection was 25.36 mmHg, and afterwards it dropped to 14.31 mmHg (p=0.004).
      There was vocal emission without stress and PES spasm improvement seen through
      the videolaryngoscopy after BT injection. CONCLUSION: We observed a reduction in
      PES pressure after BT injection, seen through CM in all the patients, with spasms
      improvement seen through videofluoroscopy.

PMID- 19575103
TI  - Vocal tract analysis in patients with vocal fold nodules, clefts and cysts.
AB  - The supraglottic plan represents an important dimension in vocal production, and
      its characterization is very important in the evaluation and treatment approach
      of dysphonic individuals. AIM: To check if certain glottic configurations are
      related to specific adjustments in the vocal tract. To use nasal and laryngeal
      fibroscopy to assess the frequency of supraglottic vocal tract adjustments in
      dysphonic women with nodules, clefts and cysts. METHODS: We assessed 31 dysphonic
      women, with age ranging between 18 and 45 years, with vocal alteration and a
      diagnosis of nodules, middle-posterior cleft and cyst, and we carried out a
      summarized evaluation of the sensory-motor and oral systems and the patients were
      submitted to video-laryngostroboscopy and nasal and laryngeal fibroscopy. Three
      distinct groups were selected: patients with bilateral nodules, clefts and cysts,
      with similar glottic configuration. Their vocal tracts were visually analyzed
      through exams of nasal and laryngeal fibroscopy, by speech and hearing therapists
      and otorhinolaryngologists, checking the following parameters: supraglottic
      constriction, larynx vertical mobility, pharyngeal constriction and tongue
      mobility. The data was statistically described and treated. RESULTS: During
      visual analysis we did not find statistically significant differences which would
      separate the glottic alterations groups. CONCLUSION: There was no correlation
      between supraglottic tract adjustments with any particular type of glottic
      alteration. These are individual behaviors that generate adjustments and justify
      the different vocal qualities in patients with the same type of laryngeal
      alteration.

PMID- 19575104
TI  - Do foreign bodies migrate through the body towards the heart?
AB  - Fixation of foreign bodies (FB), in the mucosa, can favor its migration, giving
      origin to the popular saying: 'FB walk to the heart'. AIM: Describe the
      mechanisms involved in FB migration and how to diagnose them. METHODOLOGY: From a
      sample of 3,000 foreign bodies, during 40 years, we analyzed four which had extra
      lumen migration. We analyzed clinical, radiologic, endoscopic and ultrasound data
      collected at the medical documentation service. RESULTS: Three clinical histories
      are presented, describing two fish bones and one piece of fish cartilage. FB
      shifting was analyzed in all of them. Migration started in the esophagus in two,
      one going to the aorta and the other to the neck area. In the other two,
      migration started in the pharynx, and the FB moved towards the prevertebral
      fascia and the other externalized in the submandibular region. The mechanisms and
      the risks posed to the patient, by FB migration, and the way to diagnose them are
      hereby discussed. CONCLUSIONS: The study allows us to determine that FB can move
      through the body but not towards the heart. The study also serves as a warning
      sign: in cases of prolonged histories of FB ingestion, imaging studies are
      mandatory before endoscopic examination.

PMID- 19575105
TI  - Experimental study of the tissue reaction caused by the presence of cellulose
      produced by Acetobacter xylinum in the nasal dorsum of rabbits.
AB  - Several materials have been proposed for nasal reconstruction. There is no
      consensus on which is the best. The cellulose blanket produced by bacteria may be
      a possible cartilaginous addition element to the nose. AIM: to study tissue
      reaction to cellulose in the dorsal nose of rabbits. MATERIALS AND METHODS: 22
      New Zealand rabbits were used. In 20 a cellulose blanket was implanted in the
      nasal dorsum and 2 served as controls. They were followed up through a period of
      three and six months, after which their nostrils and nasal dorsums were removed
      and histological studies were carried out on them, considering defined parameters
      of inflammation such as vascular congestion, intensity of the inflammatory
      process and presence of purulent exudate. RESULTS: The inflammatory process
      remained stable, showing its relationship with the surgical procedure and not
      with the presence of the cellulose blanket. There were no statistical differences
      in the other parameters. CONCLUSION: The cellulose blanket produced by
      Acetobacter xylinum presented good biocompatibility, remained stable during the
      entire study period, and could be considered a good material for elevating the
      nasal dorsum.

PMID- 19575106
TI  - Cleft palate children: performance in auditory processing tests.
AB  - Many children with auditory processing disorders have a high prevalence of otitis
      media, a middle ear alterations greatly prevalent in children with palatine and
      lip clefts. AIM: To check the performance of children with palate cleft alone
      (PC) in auditory processing tests. Prospective study. MATERIALS AND METHODS:
      Twenty children (7 to 11 years) with CP were submitted to sound location tests
      (SL), memory for verbal sounds (MSSV) and non verbal sounds in sequence (MSSNV),
      Revised auditory fusion (AFT-R), Pediatric test of speech
      intelligibility/synthetic sentences (PSI/SSI), alternate disyllables (SSW) and
      digit dichotic (DD). The children performances in the tests were classified in
      bad and good. RESULTS: There was no statistically significant difference between
      genders and ears. The average values obtained were 2.16, 2.42, 4.37, 60.50 ms;
      40.71 to 67.33%; 96.25 to 99.38%; 73.55 to 73.88% and 58.38 to 65.47%
      respectively for the MSSNV, MSSV, LS, AFT-R, PSI/SSI tests with ipsilateral
      (PSI/SSIMCI) and contralateral (PSI/SSI/MCC) competitive message, DD and SSW
      tests. CONCLUSION: A high percentage of children showed worse results in the AFT
      R, DD, SSW tests and in the PSI/SSIMCI tests. The best performances happened in
      the sound location tests, verbal and non-verbal sounds for sequential memory and
      for PSI/SSIMCC tests.

PMID- 19575107
TI  - Larynx cancer mortality in the State of Pernambuco - Brazil - 2000-2004.
AB  - The larynx is considered a site of the greatest occurrence of head and neck
      neoplasias, and for cancer studies, mortality is one of the most reliable health
      indicators. AIM: To study the mortality by laryngeal cancer in Pernambuco during
      2000-2004. STUDY FORMAT: Contemporary cross-sectional cohort. MATERIALS AND
      METHODS: We considered all deaths by laryngeal cancer in residents of Pernambuco
      State between 2000 and 2004, taken from the State's Mortality Information System
      (SIM/SUS). The data was analyzed through descriptive statistics, with the results
      expressed in tables, graphs and maps, using Excel version 2000 and the EpiInfo
      version 6.04 b software. RESULTS: There was little variation in the mortality
      coefficient in the years considered for study. The Sertao Mesoregion had the
      highest number of deaths and Fernando de Noronha island had the highest mortality
      rate. The patient profile found was: men, between 60-69 years, brown color,
      married, with low literacy, who died in a hospital setting. CONCLUSION: We found
      mortality stability and heterogeneity among the cities. The mortality profile
      according to social variables corroborates data found in other Brazilian States,
      except for race/color.

PMID- 19575108
TI  - Facial paralysis associated with acute otitis media.
AB  - Acute otitis media with facial paralysis is not a very frequent association. AIM:
      The goal of the present investigation was to asses the evolution of facial
      paralysis caused by acute otitis media. STUDY FORMAT: Clinical-retrospective.
      MATERIALS AND METHODS: We studied 40 patients with this association, from a total
      of 2758 cases of facial paralysis seen during this time in the department of
      facial nerve disorders. All the patients were clinically assessed and had
      epidemiological data, prognostics and evolution. RESULTS AND CONCLUSION: The
      paralysis was of sudden onset in 95% of the cases. Recovery was of 85% for grade
      I (House-Brackman) and 15% for grade II (House-Brackman). Treatment was clinical,
      with antibiotics and steroids - yielding good results. In those patients with
      electrical bad prognosis, facial nerve decompression turned their evolution into
      a favorable one.

PMID- 19575109
TI  - P300-long-latency auditory evoked potential in normal hearing subjects:
      simultaneous recording value in Fz and Cz.
AB  - The P300 is and auditory Evoked Potential, called endogenous potential because it
      reflects the functional use the individual makes of the auditory stimulus, being
      highly dependent on cognitive skills; among them we list attention and auditory
      discrimination. It is a procedure of objective evaluation; however, one that
      depends on the examiner's experience to detect wave peaks, and it is important to
      use recording methods that facilitate the response presence analysis and result
      interpretation. AIM: To analyze the P300 Long Latency Auditory Evoked Potential
      obtained through the use of two active electrodes positioned on Fz and Cz.
      MATERIALS AND METHODS: 330 individuals from both genders and age ranging between
      7 and 34 years participated in this study, they all had normal hearing and did
      not have any risk factor for mental problems. RESULTS: Results show that there
      was no statistically significant difference for N2 and P3 latency and P3
      amplitude as far as gender is concerned, nor correlation with the individual's
      age. There was a strong correlation of these measures with Fz and Cz electrode
      positioning. CONCLUSION: Fz and Cz active electrodes positioning can be
      considered one more resource to help in the P300 clinical analysis.

PMID- 19575110
TI  - Newborn hearing screening program implantation analysis at a University Hospital.
AB  - Hearing loss is more prevalent than other disorders found at birth. Efforts have
      been put up towards the early identification and treatment of hearing loss by
      means of neonatal hearing screening programs. AIM: prospective study with the
      goal of characterizing the process of implementing a Neonatal Auditory Screening
      Program (NASP) at a University Hospital. To analyze hearing loss diagnostic
      investigations in newborns, and to present proposals for NASP improvement.
      MATERIALS AND METHODS: We studied newborns (NB) submitted to Newborn Auditory
      Screening (NAS) by transient evoked otoacoustic emissions (TEOE), cochlear-eyelid
      reflex (CER) and Brainstem Evoked Auditory Potential (BEAP). RESULTS: We tested
      625 children. In the first stage, 458 NBs passed and 155 failed. 122 NBs returned
      to the second stage, and 8 underwent it because they were positive for HL risk
      factors. 12 NBs (1.9%) were referred for diagnostic investigation. Of the 5 who
      returned for the BAEP, we observed HL in two NBs. CONCLUSIONS: The program tested
      81.7% of the candidates. The program compliance rate was of 68.2%. In the first
      stage, 26.7% of the NBs failed. The program is being implemented and requires
      constant analyzes of its difficulties, aiming at solving them in order to turn
      the Universal Newborn Auditory Screening into reality.

PMID- 19575111
TI  - Characterization of tinnitus in the elderly and its possible related disorders.
AB  - Population aging it is a current reality in Brazil and tinnitus appears as a very
      prevalent symptom, having a high impact on the quality of life of elderly
      patients. AIM: To evaluate and to characterize tinnitus in this group. MATERIALS
      AND METHODS: A research questionnaire randomly given to 100 elderly patients in a
      tertiary hospital, asking about tinnitus characteristics, its impact on the life
      of the patient, and personal medical history. RESULTS: 61% of the participants
      were female, average age average was 69.53 years. The results associated with
      tinnitus features were: no-pulsatile 76%, continuous 54%, bilateral 57%, recent
      62% and alone 83%;32,5% had emotional disorders, 31.8% had sleep disorders, 22.5%
      had difficulties concentration and 13.2% had social problems; 39% classified
      their tinnitus in moderate; 35% had intense tinnitus and 26% considered it a mild
      one: as to comorbidities: relation with neurotology symptoms and hypertension; as
      for associations with audiometry findings: descending, sensorineural and
      symmetrical curves prevailed. CONCLUSIONS: Tinnitus has a relevant impact on the
      lives of the elderly; there was no correlation between the level of hearing loss
      and the level of patient dissatisfaction caused by tinnitus; and presbycusis was
      the most common finding in the audiometric tests.

PMID- 19575112
TI  - Comparative study of cell alterations in oral lichen planus and epidermoid
      carcinoma of the mouth mucosa.
AB  - Currently, much is discussed regarding the pre-malignant nature of mouth mucosa
      lichen planus. AIM: The present study aims at analyzing the alterations found in
      the epithelial cells present in the oral cavity lichen planus, comparing them to
      those found in epidermoid carcinoma. MATERIALS AND METHODS: Histological cross
      sections of oral lichen planus and epidermoid carcinoma, dyed by
      hematoxylineosin, were analyzed through light microscopy. RESULT: The most
      frequently found alterations in oral lichen planus were: an increase in the
      nucleus/cytoplasm relation (93.33%), nucleus membrane thickness (86.67%) and bi
      nucleus or multinucleous (86.67%). The Student t test (alpha=5%) revealed a
      statistically significant difference between the average number of cell
      alterations in oral lichen planus (5.87+/-1.57) and in epidermoid carcinoma
      (7.60+/-1.81). As to the types of alterations, the chi-squared test also revealed
      statistically significant differences among the lesions assessed in relation to
      the following cell alterations: nuclear excess chromatism, atypical mitoses,
      cellular pleomorphism and abnormal cell differentiation (p<0.05). CONCLUSION:
      Despite the fact that in some cases, some pathologists may make mistakes in the
      histopathological diagnosis of oral lichen planus, the results obtained in this
      study show that the alterations present in oral lichen planus differ considerably
      from those seen in epidermoid carcinoma, thus showing how distinct these two
      diseases are.

PMID- 19575113
TI  - The role of intraoperative frozen sections for thyroid nodules.
AB  - The role of intraoperative frozen sections (FS) during thyroidectomy is
      controversial. AIM: to evaluate the role of FS for thyroid nodules management.
      PATIENTS AND METHODS: All patients who had thyroid surgery for nodular disease
      and previous USG-guided FNAB in 2006 were prospectively analyzed. They underwent
      intraoperative FS evaluation, and the biopsy material was classified as benign,
      malignant or follicular neoplasm. FNAB, FS and paraffin sections were compared.
      RESULTS: Under the FS, 54% of the nodules were benign, 30% were follicular
      neoplasms, and 16% were malignant. All cases considered benign and malignant
      under the FS evaluation were confirmed through the histological 'paraffin'
      analysis. Since it is not considered a definitive indication for total
      thyroidectomy, if the follicular neoplasms were classified as 'benign' under the
      FS, their sensitivity, specificity, positive and negative predictive values and
      global diagnostic accuracy were 69%, 100%, 100%, 91,5% e 77%, respectively. Among
      the 42 cases classified as 'follicular neoplasm' under the FNAB, in 1 case the FS
      conclusion was for papillary carcinoma, in 3 cases as benign (all confirmed
      through the 'paraffin'); and 38 cases continued as 'follicular pattern', being 29
      follicular adenomas and 9 carcinomas through the 'paraffin'. CONCLUSION: The FS
      is only indicated when the FNAB reports 'follicular neoplasm'.

PMID- 19575114
TI  - A method for measuring the length of the cochlea through magnetic resonance
      imaging.
AB  - We know that hearing impairment affects a large part of the population. In cases
      of profound and bilateral hearing loss, children may have problems in speech
      development, as well as communication and socialization. Cochlear implants have
      been used as a treatment option in these cases. Today, inner ear MRI is a
      mandatory test in the preoperative evaluation of these individuals. In our daily
      routines, we wonder whether MRI can provide not only qualitative, but also
      quantitative data, with real cochlear linear values built from three dimension
      images. AIMS: The aim of the present investigation is to propose a method to
      obtain MRI cochlear length measures from the temporal bones of cadavers. MATERIAL
      AND METHODS: We assessed three dimensional images from the cochlea of six
      cadavers. By overlapping digitalized rulers on these images it was possible to
      measure cochlear length. RESULTS: These measures varied between 17 and 26.5
      millimeters. CONCLUSIONS: We have concluded that it was possible to measure
      cochlear length from three dimensional MRI images, by employing the method hereby
      proposed.

PMID- 19575115
TI  - Functional alterations of the stomatognathic system in patients with allergic
      rhinitis: case-control study.
AB  - Mouth breathing can cause structural and functional alterations to the
      stomatognathic system. AIM: The aim of this investigation was to study breathing,
      chewing, swallowing and speaking alterations present in patients with allergic
      rhinitis and associate it to rhinitis symptom intensity. MATERIALS AND METHODS:
      170 patients between the ages of 6 and 55 years were prospectively evaluated in
      this study, all of them underwent both otorhinolaryngological and speech
      evaluation. Data on breathing, chewing, swallowing and speaking was gathered, as
      well as data from the medical evaluation. The data was compared and statistically
      analyzed. RESULTS: The difference in signs and symptoms' score between GR and GC
      was significant. We noticed a significant difference between GR and GC in
      breathing, chewing and swallowing. We observed a significant association between
      the score of nasal obstruction and the intensity of breathing and chewing
      alterations. CONCLUSION: Patients with allergic rhinitis have functional
      alterations in their stomatognathic system and an increase in nasal obstruction
      scores can be considered as a indication of such alterations.

PMID- 19575116
TI  - Correlation between voice and life quality and occupation.
AB  - Dysphonia may impair the quality of communication and social relations of people,
      thereby directly affecting quality of life. It is common knowledge amongst
      professionals involved with the treatment of voice disorders the need for
      objective protocols to evaluate voice quality and measure its impact on the
      individual's quality of life. AIM: To associate life quality with the degree of
      dysphonia and professional voice use in a group of dysphonic patients. MATERIALS
      AND METHODS: A prospective clinical study was undertaken with a group of
      dysphonic patients using an internationally validated voice-related quality-of
      life protocol. A statistical analysis of the results was carried out, not
      distinguishing between those who use their voices professionally and those who
      don't. RESULTS: Dysphonia had an impact on the quality of life of all patients.
      There was no statistically significant difference between the groups -
      professional users and non-users of their voices; however, considering the groups
      separately, this correlation was significant only in the group of patients who do
      not use their voices professionally. CONCLUSION: Dysphonia affected the quality
      of life of all subjects regardless of their voice use.

PMID- 19575117
TI  - Topical use of adrenaline in different concentrations for endoscopic sinus
      surgery.
AB  - The ideal adrenaline concentration remains unknown. AIM: Compare topical
      adrenaline solutions in different concentrations. STUDY DESIGN: Prospective,
      double blind, randomized trial. PATIENTS AND METHODS: 49 patients divided in 3
      groups underwent endoscopic sinus surgery, using only topical solutions of
      adrenaline in different concentrations (1:2,000, 1:10,000 and 1:50,000). We
      compared the duration of surgery, intra-operative bleeding, plasmatic levels of
      catecholamines, hemodynamic parameters and changes in heart rhythm. RESULTS:
      Surgery time was shorter in the group using adrenaline 1:2,000, which also showed
      less bleeding in all evaluations (objective and subjective - p < 0.0001).
      Plasmatic levels of epinephrine rose in all groups, more sharply in the 1:2,000
      group. There was a trend towards elevation of blood pressure in the groups using
      adrenaline 1:2,000 and 1:10,000, with a greater occurrence of hypertensive peaks.
      DISCUSSION: We found a very significance bleeding difference favoring the
      1:2,000. The blood pressure elevation in the 1:2,000 and 1:10,000 groups was
      progressive but very slow throughout the procedure, which could be associated
      with the anesthesia technique. CONCLUSION: We favor the use of topical adrenalin
      1:2,000 due to a clear superiority in hemostasis. Further investigation is needed
      to corroborate our findings.

PMID- 19575118
TI  - Vestibular evaluation using videonystagmography of chronic zinc deficient
      patients due to short bowel syndrome.
AB  - The presence of zinc in the auditory pathways and its probable participation in
      tinnitus and hearing loss are known facts, although there are no clinical trials
      and experimental studies showing the impact of hypozincemia in the vestibular
      system and zinc existence in the vestibular pathway, respectively. AIM: This
      study is an attempt to correlate hypozincemia and abnormal vestibular function.
      METHODS: This is a clinical retrospective case study where nine patients
      suffering of chronic zinc deficiency had their serum zinc determined and were
      submitted to videonystagmography. Results were compared to a normal (control)
      group. RESULTS: All vestibular test parameters were altered when we compared
      experimental and control groups. CONCLUSION: Comparison between groups shows
      significant differences in many aspects of the vestibular analysis and calls our
      attention towards a possible participation of zinc on the genesis of vestibular
      disorders.

PMID- 19575119
TI  - Oral erythroplakia and speckled leukoplakia: retrospective analysis of 13 cases.
AB  - Erythroplakia and speckled leukoplakia are oral precancerous lesions that have a
      high potential for malignant transformation. AIM: A retrospective analysis was
      conducted to investigate the clinicopathologic features of 13 cases of oral
      erythroplakia and speckled leukoplakia in patients who were seen at a center
      specialized in stomatology and Histopathological diagnosis of oral diseases.
      MATERIALS AND METHODS: All cases diagnosed with erythroplakia and speckled
      leukoplakia between 1978 and 2006 were retrieved from the service archives.
      RESULTS: The lesions exhibited a predilection for males with a female-to-male
      ratio of 1:3.3. Mean age was 57 years old and soft palate was the site affected
      in 77% of the cases. Pain symptoms were reported by 61.5% of the patients and
      association with risk factors such as smoking and excessive alcohol intake was
      seen in 100% and in 46% of the cases, respectively. The lesions showed epithelial
      dysplasia, where more than 50% were diagnosed as in situ or invasive carcinoma.
      CONCLUSIONS: Despite low prevalence, oral homogeneous erythroplakia and speckled
      leukoplakia show Histopathological alterations vary from epithelial dysplasia to
      invasive carcinoma. These lesions must be included among those oral lesions with
      the highest potential for malignant tranformation.

PMID- 19575120
TI  - Audiologic features of elderly with Benign Paroxysmal Positional Vertigo.
AB  - Benign Paroxysmal Positional Vertigo (BPPV) is one of the most common causes of
      dizziness; it constitutes the most common vestibular disorder in the elderly with
      vertigo. Its characteristic clinical aspect is dizziness at head movement, with
      not hearing alteration. AIM: This paper aims at studying the audiologic
      characteristics of elderly with BPPV of the posterior semicircular canal.
      MATERIALS AND METHODS: We carried out a retrospective analysis of threshold tonal
      audiometry exams of 37 senior citizens with posterior semicircular canal BPPV and
      also of 37 elderly without complaints of dizziness and/or vertigo, and we studied
      the audiologic characteristics of the two groups. RESULTS: Both groups had high
      rates of hearing loss, especially the descending curve sensorineural type, and
      there was no statistically significant difference between the groups. CONCLUSION:
      Having such data, we can conclude that posterior semicircular canal BPPV has no
      impact on the hearing loss features of senior citizens; nonetheless, because of
      the spontaneous degeneration of the vestibulocochlear system, such population has
      a prevalence of hearing loss.

PMID- 19575121
TI  - Nasal valve: anatomy and physiology.
AB  - The anterior portion of the nasal cavities, from the nostril to the nasal valve
      (NV), is the place of highest nasal resistance to airflow, paramount to nasal
      physiology. There are different terminologies for the same anatomic structures in
      the literature. AIM: The aim of this paper was to study the NV function and
      define clearly the structures of the anterior portion of the nasal cavities,
      mainly the region of the NV. CONCLUSION: Internum ostium is the anterior segment
      and isthmus nasi is the posterior segment of the NV region.

PMID- 19575122
TI  - Diversity of allergen exposure: implications for the efficacy of environmental
      control.
AB  - The prevalence of allergic diseases such as asthma, rhinitis, allergic
      conjunctivitis and atopic dermatitis has increased in the last decades. The
      relationship between allergen exposure, atopic sensitization and development of
      allergic diseases is widely described in the literature. AIM: To evaluate
      measures for reducing allergen exposure as part of the treatment of allergic
      diseases. METHODS: An analysis was made of previous studies on allergen exposure
      done with a similar methodology in the central region of Brazil; the study
      included homes, hotels, cinemas, cars, taxis, buses and scholar transportation.
      RESULTS: High levels of Der p 1 and Der f 1 mite allergens were found in a large
      proportion of the sample in most of the environments included in those studies;
      there were higher levels of pet allergens in cars and school transportation
      vehicles. CONCLUSION: The diversity of allergen exposure demonstrates the need
      for education about allergic diseases for patients and their families, as well as
      measures of reducing allergens in homes. This should be part of a global strategy
      of the management of allergic diseases, given that individuals live in society,
      not only in their houses.

PMID- 19575123
TI  - Oncocytic papilloma.

PMID- 19575124
TI  - Unusual coexistence of oral lymphoepithelial cyst and benign migratory glossitis.

PMID- 19575125
TI  - Retropharyngeal abscess and stridor in infants.

PMID- 19575126
TI  - Glandular odontogenic cyst: an uncommon entity.

PMID- 19575127
TI  - [Experimental models of traumatic brain injury].
AB  - AIM: To provide a summary of the different experimental models of traumatic brain
      injury (TBI) designed under both in vivo and in vitro conditions. A
      comprehensible review of the specific types of brain lesions induced, as well as
      the technical details to reproduce each model at the laboratory is given.
      DEVELOPMENT: Outcome of patients suffering from a TBI has significantly improved
      with the rapid application of vital supporting measures in addition to a strict
      control of blood and intracranial pressure at the intensive care units. However
      no specific treatment for post-traumatic brain lesions has proven as efficacious
      in the clinical settings. A deeper knowledge of the physiopathological events
      associated with TBI is necessary for the development of new specific therapies.
      Due to the heterogeneity of the human TBI, each experimental model has been
      designed to reproduce a different type of brain lesion. Experimental TBI models
      allow the study of the dynamic evolution of brain injuries under controlled
      conditions. Usefulness of experimental models is limited by their reliability and
      reproducibility among different researchers. Small rodents have been the
      preferred animals to reproduce TBI injuries, mainly due to the similar cerebral
      physiology shared by these animals and the human beings. CONCLUSION: The use of
      experimental models of TBI is the most appropriate tool to study the mechanisms
      underlying this type of injury. However their simplicity precludes an exact
      reproduction of the heterogeneous cerebral damage observed in clinical settings.
      This could be the main reason for the discrepancies observed in the therapeutic
      effects of treatments between experimental and clinical studies.

PMID- 19575128
TI  - Calpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves
      neurologic function after traumatic spinal cord injury in rats.
AB  - BACKGROUND: An increase in the level of intracellular calcium activates the
      calcium-dependent neutral protease calpain, which in turn leads to cellular
      dysfunction and cell death after an insult to the central nervous system. In this
      study, we evaluated the effect of a calpain inhibitor, AK 295, on spinal cord
      structure, neurologic function, and apoptosis after spinal cord injury (SCI) in a
      murine model. METHODS: Thirty albino Wistar rats were divided into 3 groups of 10
      each: the sham-operated control group (group 1), the spinal cord trauma group
      (group 2), and the spinal cord trauma plus AK 295 treatment group (group 3).
      After having received a combination of ketamine 60 mg/kg and xylazine 9 mg/kg to
      induce anesthesia, the rats in groups 2 and 3 were subjected to thoracic trauma
      by the weight drop technique (40 g-cm). One hour after having been subjected to
      that trauma, the rats in groups 2 and 3 were treated with an intraperitoneal
      injection of either dimethyl sulfoxide 2 mg/kg or AK 295 2 mg/kg. The effects of
      the injury and the efficacy of AK 295 were determined by an assessment of the
      TUNEL technique and the results of examination with a light microscope. The
      neurologic performance of 5 rats from group 2 and 5 from group 3 was assessed by
      means of the inclined plane technique and the modified Tarlov's motor grading
      scale 1, 3, and 5 days after spinal cord trauma. FINDINGS: Light-microscopic
      examination of spinal cord specimens from group 2 revealed hemorrhage, edema,
      necrosis, and vascular thrombi 24 hours after trauma. Similar (but less
      prominent) features were seen in specimens obtained from group 3 rats. Twenty
      four hours after injury, the mean apoptotic cell numbers in groups 1 and 2 were
      zero and 4.57 +/- 0.37 cells, respectively. In group 3, the mean apoptotic cell
      number was 2.30 +/- 0.34 cells, a value significantly lower than that in group 2
      (P < .05). Five days after trauma, the injured rats in group 2 demonstrated
      significant motor dysfunction (P < .05). In comparison, the motor scores
      exhibited by group 3 rats were markedly better (P < .05). CONCLUSIONS: AK 295
      inhibited apoptosis via calpaindependent pathways and provided neuroprotection
      and improved neurologic function in a rat model of SCI. To our knowledge, this is
      the first study to evaluate the use of AK 295, a calpain inhibitor, after SCI.
      Our data suggest that AK 295 might be a novel therapeutic compound for the
      neuroprotection of tissue and the recovery of function in patients with a SCI.

PMID- 19575129
TI  - Bioabsorbable osteofixation devices in craniosynostosis. Clinical experience in
      216 cases.
AB  - INTRODUCTION: The pursuit of bone fixation systems capable of affording
      appropriate stability for osteosynthesis has gone through several stages from the
      use of metal wires, plates, and screws to the current stage of bioabsorbable
      systems. In our Pediatric Neurosurgery Service and Craniofacial Surgery Unit we
      began employing these systems in June 1997. The object of this paper is to
      present a review of the bioabsorbable materials most commonly used in pediatric
      age, and more specifically in treating craniosynostosis, to describe the
      characteristics of each one of them and our experience. PATIENTS AND METHODS:
      From June 1997 to May 2006 we implanted bioabsorbable fixation systems in 216
      patients diagnosed with craniosynostosis. Age at treatment ranged between 4 and
      24 months (mean age 6.38 months). Brain computed tomography (CT) scans, and three
      dimensional (3-D) reconstruction of CT scans were performed before and after
      treatment. An 82: 18 L-lactic acid: glycolic acid copolymer was used in 92.2% of
      these cases, and a 70:30 L-lactic acid: D-lactic acid copolymer was used in the
      remaining 7.8% of cases. The follow-up of the patients ranged between six months
      and five years. RESULTS: There was no displacement of bioabsorbable plates or
      screws in any case. In one case (0.46%), radiological imaging revealed osteolysis
      underneath the implant eight months after the surgical procedure. Prominences
      caused by the plates and screws employed were visible in two cases (0.93%). We
      found fractures in the osteosynthesis mesh in two patients (0.93%). Four patients
      (1.85%) presented local inflammation. No alterations of cranial morphology
      secondary to inadequate stability were observed. CONCLUSIONS: 1) Bioabsorbable
      fixation systems provide excellent stability during the bone "healing" period,
      without a higher complication rate than with other systems. 2) They help the bone
      grafts keep their remodeled shape. 3) They promote reossification by preventing
      the bone grafts from moving after osteosynthesis. 4) No interference with normal
      growth of the cranial vault has been observed.

PMID- 19575130
TI  - [Cranial lesions due to forceps delivery].
AB  - Deliveries with forceps or vacuum-extraction increase the incidence of perinatal
      craneoencephalic lesions, for which reason cesarean sections are performed more
      frequently. We report 3 cases of cranial lesions due to forceps deliveries, 2
      with depressed skull fractures and 1 with a depressed fracture and an associated
      epidural hematoma. Diagnosis is made on clinical and radiological founds with CT
      scan or MRI. Treatment is surgical and consists of elevation of the depressed
      fracture and evacuation of the hematoma. The correct use of forceps is very
      important to avoid this kind of lesions in the newborn, especially in cases of
      difficult delivery.

PMID- 19575131
TI  - [Two cases of brain haemorrhage secondary to developmental venous anomaly
      thrombosis. Bibliographic review].
AB  - We report two cases of intracraneal brain haemorrhage secondary to developmental
      venous anomaly trombosis recently treated at our Department. First patient was a
      28-year old woman on oral contraceptive treatment for a month who was referred to
      our Department with sudden-onset conscious level deterioration after presenting
      24 hours previously with headache, vomits and hemiparesis. Computed Tomography
      revealed a predominant hypodense area containing hyperdense foci causing mild
      mass effect and midline-shift in keeping with a haemorrhagic infarction occupying
      almost completely the right frontal lobe. On CT, magnetic resonance (MR) and
      magnetic resonance angiography (MRA) there was a prominent tubular structure
      adjacent to the hematoma in keeping with a partly thrombosed vessel. Urgent
      craniotomy and partial hematoma evacuation was performed. Digital subtraction
      angiography confirmed the presence of a filling defect within the draining vein
      of a typical caputmedusae pattern developmental venous anomaly (DVA). Systemic
      anticoagulation was started and four days after surgery sedation was reversed and
      the patient awoke with normal conscious level although mild (4/5) hemiparesis
      persisted. Second patient was a 38-year old male evaluated in the Emergency
      Department due to tonic-clonic seizures in the left side followed by altered
      sensation in the same distribution. Initial CT revealed an intracranial bleed.
      After contrast administration there was an anomalous vessel in the same location
      that was confirmed angiographically represented a partly thrombosed DVA.
      Conservative management was favoured and the patient was discharged from hospital
      without clinical neurological deficits.

PMID- 19575132
TI  - [Isolated mesencephalic stroke related to a ruptured intracranial dermoid cyst].
AB  - Dermoids cysts are embrionary benign lesions that comprise approximately 0.04
      0.25% of all intracranial tumors. Occasionally they break and spread their
      content into subarachnoid space and/or lateral ventricles causing several acute
      or delayed symptoms. Debut of this type of tumor as acute stroke is poorly
      reflected in literature. We present a 26-year-old woman with a isolated
      mesencephalic infarct secondary to spontaneous rupture of a dermoid cyst. We
      discuss the possible pathophysiological mechanisms for this condition and review
      the literature.

PMID- 19575133
TI  - [Symptomatic xanthogranuloma of the lateral ventricle].
AB  - Xanthogranulomas of the choroid plexus is a benign tumour of uncertain etiology,
      usually asymptomatic. We report a case of symptomatic xanthogranuloma of the left
      lateral ventricle with edema in adjacent white matter, in a 62-year-old man with
      seizures.

PMID- 19575134
TI  - Intradural extramedullary spinal hydatidosis: case report.
AB  - The parasitic tapeworm Echinococcus granulosis causes hydatid disease, which is
      rarely encountered in nonendemic regions. It is a progressive disease with
      serious morbidity risks. Rarely, these cysts are found in the spine. They are
      mainly found epidurally, originating from direct extension from pulmonary,
      abdominal or pelvic infestation. Nevertheless, the main mechanism for intradural
      involvement is not yet clear. Antihelminthic treatment should be administered for
      a long period following early decompressive surgery. We report a case of
      recurrent hydatid disease that presented unusual intradural dissemination.
      Prognosis for spinal hydatid disease remains very poor and comparable to that of
      a malignant neoplasm.

PMID- 19575135
TI  - Bilateral paramedian thalamic and mesencephalic infarcts after basilar tip
      aneurysm coiling: role of the artery of Percheron.
AB  - Aneurysm embolization using Guglielmi detachable coils (GDC) is gaining
      acceptance as a viable alternative for surgery in the treatment of aneurysms.
      Recent reports describe a significant rate of thromboembolic complications.
      Thalamic and midbrain blood supply can arise from complex anatomical variations.
      The rare variation: "artery of Percheron", is a solitary arterial trunk arising
      from one of the proximal segments of a posterior cerebral artery and supplies the
      paramedian thalami and rostral midbrain bilaterally. We describe a patient that
      underwent elective endovascular treatment for a basilar tip aneurysm using GDC
      and stents in each PCA; 12 hours later patient was comatose and not following
      commands. Sequential magnetic resonance imaging (MRI) of brain showed bilateral
      paramedian thalamic and mesencephalic infarcts presumably secondary to artery of
      Percheron occlusion. Thromboembolic event related to the use of the GDC
      embolization and stents is a rare clinical sequelae, but catastrophic. The use of
      antiplatelets agents should be reinforced in the scenario. When bilateral medial
      thalamic and midbrain infarcts are found, occlusion of the artery of Percheron
      should be considered. Angiography may not b helpful and lack of visualization of
      the artery does not exclude its presence. In this case the MRI findings confirmed
      the presence of the infarction based on the anatomical distribution.

PMID- 19575136
TI  - [A new case of "olfactory schwannoma"; presentation and literature review].
AB  - We report the case of a 54-year-old man who presented at the Emergency Department
      with intense headache of 6-days duration and sporadic nominal dysphasia. He did
      not present anosmia and the rest of the examination was normal. The emergency CT
      and the posterior cerebral MR showed a great subfrontal extra-axial mass of 7 x 6
      x 5 cm, over the right side of the cribiform plate, hetereogeneously enhancing
      after gadolinium administration. Preoperative diagnosis was olfactory groove
      meningioma. After total removal by bifrontal craniotomy the histopathological
      diagnosis was schwannoma of the conventional type. Owing to the unusual frequency
      of this kind of tumors (26 to the date), we review the literature, the possible
      radiological differences with olfactory groove meningiomas and the different
      theories about their origin.

PMID- 19575137
TI  - [The current health system and the spirit of May 68].
AB  - Forty years after the 68 May revolt, we have thought of interest to retrieve part
      of the revolutionary ideology concerning the role of medical practice in the
      society they would to change. In essence they said: the current organization of
      health care, although masked by mysticism, provides political support to the
      dominant class and favours socio-economic exploitation. Relevant features of
      medical structures, the hospital, the traditional medical mentality, the
      biologistic paradigm, etc. reinforce the hierarchical order in the capitalist
      society.

PMID- 19575138
TI  - The interaction of obesity and psychological distress on disability.
AB  - BACKGROUND: Prior research has shown that psychological problems interact with
      various chronic medical conditions to amplify disability, but no study has
      investigated this effect in obesity. The aim of this study was to evaluate the
      synergistic interaction of psychological distress and obesity on functional
      disability in an adult community sample. METHODS: Cross-sectional data were
      obtained from the 2005 Canadian Community Health Survey, a nationally
      representative sample of 53,416 respondents aged 18 years or older. Our outcome
      measures were self-reported disability days and self-rated health. Our covariates
      of interest were non-specific psychological distress (Kessler K10 scale) and body
      mass index (BMI). Odds ratios of disability measures were estimated by
      psychological distress and weight status from logistic regressions, adjusted for
      sociodemographic and clinical variables. RESULTS: Disability status was more
      frequent in individuals with obesity and psychological distress than in those
      with either obesity or psychological distress alone. Adjusted odds ratios
      increased progressively across BMI and psychological distress categories.
      Significant interactions were found for (a) obesity class I (BMI between 30.0 and
      34.9 kg m(-2)) and high psychological distress; and (b) obesity class II-III (BMI
      > 35 kg m(-2)) and moderate to high distress. CONCLUSION: The results suggest a
      strong association between psychological distress, obesity and disability.
      Addressing psychological distress in obese individuals might reduce the public
      health burden of comorbid obesity and psychological distress by tackling
      disability.

PMID- 19575139
TI  - Urogynecology in Taiwan: past, present and future.

PMID- 19575140
TI  - Peripubertal estrogen levels and physical activity affect femur geometry in young
      adult women.
AB  - The growing skeleton is particularly responsive to exercise around the time of
      puberty, suggesting a possible role for estrogen in mechanical adaptation in
      young women. We assessed femoral neck strength index at age 17 in young women
      with varying adolescent physical activity levels and E2 levels in the first 3
      years after menarche. The results indicate that both E2 levels in the first year
      after menarche and adolescent physical activity are positively associated with
      bone strength in young adulthood, such that hormone levels may modify human
      osteogenic responses to exercise. INTRODUCTION: It is well established that
      physical activity contributes to bone strength in young females, but less is
      known about how peripubertal estrogen affects skeletal responses to exercise.
      METHODS: We used data from 84 participants in the Penn State Young Women's Health
      Study to test the prediction that young women who (1) had higher E2 levels during
      the first year after menarche or (2) were more physically active in adolescence
      will have greater bone strength at the end of adolescence. Subjects were divided
      into tertiles of physical activity and of E2 level in the first, second, and
      third postmenarchal years, and femoral strength was calculated from dual-energy X
      ray absorptiometry scans of the proximal femur using hip structure analysis.
      RESULTS: At age 17, subjects with the highest E2 levels in year 1 after menarche
      had 5-14% greater strength in the narrow neck and intertrochanteric region, and
      the most active subjects had 10-11% greater strength in the femoral narrow neck
      vs. less active girls. CONCLUSIONS: This study suggests that both physical
      activity and peripubertal estrogen have important influences on young adult bone
      strength and that hormone levels may be mediators of human osteogenic responses
      to exercise.

PMID- 19575141
TI  - Radiofrequency ablation for the treatment of autonomously functioning thyroid
      nodules.
AB  - BACKGROUND: Some patients with autonomously functioning thyroid nodules (AFTN)
      are not suitable for surgery or radioiodine therapy. Therefore, minimally
      invasive alternative treatments, such as ethanol ablation or radiofrequency
      ablation (RFA), are necessary. METHODS: This study included nine patients (4
      toxic and 5 pretoxic patients; male to female ratio = 1:8; mean age, 47 +/- 17
      (range, 25-71) years) who were not eligible for surgery or radioiodine therapy.
      All of the patients showed hot nodule with suppression of normal thyroid gland in
      (99m)Tc pertechnetate scintigraphy. RFA was performed using a 17- and 18-gauge
      internally cooled electrode. Nodule volume, thyroid function, scintigraphy,
      symptom score (visual analogue scale, 0-10 cm), cosmetic grading score (4-point
      scale), and complications were evaluated before treatment and at 1, 3, and 6
      months follow-up. RESULTS: Mean volume of the index nodule was 14.98 +/- 25.53
      (range, 0.29-82.29) mL. After RFA it decreased at 1 month (12.01 +/- 25.97 mL, p
      = 0.015), 3 months (7.27 +/- 15.13 mL, p = 0.011), 6 months (8.27 +/- 21.29 mL, p
      = 0.008), and the last month (7.57 +/- 19.99 mL, p = 0.008). Initial mean T3,
      fT4, and TSH were 156.2 +/- 42.1 ng/dL, 1.73 +/- 0.40 ng/dL, and 0.052 +/- 0.087
      mU/mL, respectively. A significant improvement of mean T3, fT4, and TSH were
      observed at last follow-up (T3: 116.8 +/- 20.7 ng/dL, p = 0.015; fT4: 1.37 +/-
      0.26 ng/dL, p = 0.036; TSH: 1.454 +/- 1.756 mU/mL, p = 0.012). After ablation,
      four patients became a cold or normal scan and five remained as a hot nodule. The
      mean symptom and cosmetic grading score was reduced from 2.4 +/- 1.7 to 0.6 +/-
      0.7 (p = 0.011) and from 3.1 +/- 1.2 to 1.4 +/- 1.0 (p = 0.017), respectively. No
      major complications were encountered. CONCLUSIONS: RFA seems to be effective and
      safe for the treatment of AFTN.

PMID- 19575142
TI  - Metastasis-associated protein 1 (MTA1) overexpression is closely associated with
      shorter disease-free interval after complete resection of histologically node
      negative esophageal cancer.
AB  - BACKGROUND: The purpose of the present study was to investigate the expression of
      metastasis-associated protein 1 (MTA1) and its relationship to the disease-free
      interval after resection of pathologic N0 (pN0) esophageal squamous cell cancer
      (ESCC). METHODS: The subjects were 90 patients who successfully underwent
      complete resection of pN0 ESCC between May 2001 and May 2003. Immunohistochemical
      staining for MTA1 protein was performed using the avidin-biotin peroxidase
      complex method. Log-rank test was performed to compare the disease-free interval,
      and Cox regression multivariate analysis was performed to judge independent
      prognostic factors. RESULTS: Metastasis-associated protein 1 overexpression was
      detected in 40 esophageal cancer tissues. Disease-free interval was significantly
      associated with MTA1 protein overexpression (p = 0.015). The overall 5-year
      survival rate was 45.6%, the 5-year survival rate of patients with MTA1 protein
      overexpression was significantly lower than that of those without overexpression
      (25.0 versus 62.0%; p < 0.001). The results of multivariate analysis confirmed
      that T status and MTA1 protein overexpression were independent prognostic
      factors. CONCLUSIONS: Metastasis-associated protein 1 overexpression was detected
      in pN0 ESCC and was significantly correlated with shorter disease-free interval.
      T status and MTA1 protein overexpression were both independent prognostic
      factors. These findings suggested MTA1 might be a predictor of relapsing
      phenotype and a prognostic factor in esophageal cancer.

PMID- 19575143
TI  - Ischemic preconditioning confers antiapoptotic protection during major
      hepatectomies performed under combined inflow and outflow exclusion of the liver.
      A randomized clinical trial.
AB  - BACKGROUND: Extensive experimental studies and a few clinical series have shown
      that ischemic preconditioning (IPC) attenuates oxidative ischemia/reperfusion
      (I/R) injuries in liver resections performed under inflow vascular control.
      Selective hepatic vascular exclusion (SHVE) employed during hepatectomies
      completely deprives the liver of blood flow, as it entails simultaneous clamping
      of the portal triad and the main hepatic veins. The aim of the present study was
      to identify whether IPC can also protect hepatocytes during liver resections
      performed under SHVE. METHODS: Patients undergoing major liver resection were
      randomly assigned to have either only SHVE (control group, n = 43) or SHVE
      combined with IPC--10 min of ischemia followed by 15 min of reperfusion before
      SHVE was applied (IPC group, n = 41). RESULTS: The two groups were comparable
      with regard to age, liver resection volume, blood loss and transfusions, warm
      ischemic time, and total operative time. In liver remnant biopsies obtained 60
      min post-reperfusion, IPC patients had significantly fewer cells stained positive
      by TUNEL compared to controls (19% +/- 8% versus 45% +/- 12%; p < 0.05). Also IPC
      patients had attenuated hepatocyte necrosis, systemic inflammatory response, and
      oxidative stress as manifested by lower postoperative peak values of aspartate
      transaminase, interleukin-6, interleukin-8, and malondialdehyde compared to
      controls. Morbidity was similar for the two groups, as were duration of intensive
      care unit stay and extent of total hospital stay. CONCLUSIONS: In major
      hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate
      apoptotic response of the liver remnant, possibly through alteration of
      inflammatory and oxidative pathways.

PMID- 19575144
TI  - Long-term outcome and survival of surgically treated supratentorial low-grade
      glioma in adult patients.
AB  - PURPOSE: The appropriate management of low-grade gliomas is still a matter of
      debate. So far, there are no randomized studies that analyze the impact of
      surgical resection on patient outcome. The value of the data obtained from the
      few retrospective reports available is often limited. PATIENTS AND METHODS: In
      the present study, we performed an analysis on data of 130 adult low-grade glioma
      patients. Extent of the resection was evaluated in correlation to the overall
      survival (OS) and progression-free survival (PFS) using Cox regression
      multivariate analysis. RESULTS: Extended surgery was shown to prolong OS and PFS
      significantly. Re-surgery in the case of a tumor relapse has a significant impact
      on OS and PFS, too. CONCLUSIONS: In summary, we could retrospectively evaluate a
      large case series of well-defined low-grade gliomas patients with a long follow
      up period showing that extended surgery would be the most effective therapy for
      low-grade glioma patients even in recurrent diseases.

PMID- 19575145
TI  - On the occurrence of Cebus flavius (Schreber 1774) in the Caatinga, and the use
      of semi-arid environments by Cebus species in the Brazilian state of Rio Grande
      do Norte.
AB  - Cebus flavius is a recently rediscovered species and a candidate for the 25 most
      endangered primate species list. It was hypothesized that the distribution of C.
      flavius was limited to the Atlantic Forest, while the occurrence of C.
      libidinosus in the Rio Grande do Norte (RN) Caatinga was inferred, given its
      occurrence in neighboring states. As a result of a survey in ten areas of the RN
      Caatinga, this paper reports on four Cebus populations, including the first
      occurrence of C. flavius in the Caatinga, and an expansion of the northwestern
      limits of distribution for the species. This C. flavius population may be a rare
      example of a process of geographic distribution retraction, and is probably the
      most endangered population of this species. New areas of occurrence of C.
      libidinosus are also described. Tool use sites were observed in association with
      reports of the presence of both capuchin species.

PMID- 19575146
TI  - Phase II study of gemcitabine in combination with vinorelbine versus gemcitabine
      followed by vinorelbine for metastatic breast cancer.
AB  - BACKGROUND: No clear data are available concerning the superiority of combination
      chemotherapy to sequential therapy using agents beyond 1st or 2nd line
      chemotherapy for treating patients with metastatic breast cancer. METHODS:
      Patients were randomized to receive a combination of gemcitabine and vinorelbine
      or gemcitabine until disease progression followed by vinorelbine monotherapy.
      Quality of life was assessed using EORTC QLQ-C30 questionnaires. RESULTS: Forty
      two patients were randomized to the combination arm and 40 were randomized to the
      sequential arm. Baseline characteristics were well balanced between the arms. The
      median number of chemotherapy cycles was 4 (range, 1-23) for the combination arm
      and 6 (range, 1-25) for the sequential arm. Patients receiving combination
      therapy had a higher composite response rate (26.8% vs. 12.5%; P = 0.106) but a
      shorter median time to treatment failure (3.6 vs. 4.4 months, P = 0.252) as
      compared to patients receiving sequential monotherapy. Median overall survival
      for the combination and sequential arms was 10.6 months and 8.9 months,
      respectively (P = 0.436). Toxicities were manageable and similar in both arms.
      Quality of life measurements in global health, role, and social function were
      superior in the combination arm (P < 0.05). CONCLUSIONS: Combined gemcitabine and
      vinorelbine therapy appears comparable to sequential monotherapy for heavily
      pretreated patients with metastatic breast cancer as demonstrated by improved
      quality of life outcomes with similar therapeutic efficacies and incidences of
      adverse events.

PMID- 19575147
TI  - Information gaps for patients requiring craniotomy for benign brain lesion: a
      qualitative study.
AB  - Doctor-patient communication in the setting of a life-threatening illness poses
      considerable challenges. This study aimed to determine the information needs of a
      subset of neurosurgical patients. Qualitative case study methodology was used.
      Twenty-five semi-structured interviews were conducted with ambulatory adult
      patients who had undergone surgery for a benign brain tumor, arteriovenous
      malformation, or unruptured aneurysm. Interviews were digitally audio recorded
      and transcribed, and the data subjected to thematic analysis. Six overarching
      themes emerged from the data: (1) the amount of information patients want varies;
      (2) the type of information needed is not limited to information about treatment
      options and risks; (3) patients engage in independent information seeking for a
      variety of reasons; (4) patients consider compassion from their surgeon as
      important; (5) direct communication with the surgeon post-operatively is very
      important; and (6) patients' information needs are greatest post-operatively.
      Many patients felt that the amount and quality of information they received was
      not sufficient, particularly regarding post-operative recovery and long-term life
      issues, leading many to do their own research. The findings from this study
      emphasize the need for improved communication with patients so they can
      participate meaningfully in choices about their treatment, give a truly informed
      consent, and effectively participate in their own recovery.

PMID- 19575148
TI  - [11C]-L-methionine positron emission tomography in the management of children and
      young adults with brain tumors.
AB  - Only a few Methyl-[11C]-L-methionine (MET) positron emission tomography (PET)
      studies have focused on children and young adults with brain neoplasm. Due to
      radiation exposure, long scan acquisition time, and the need for sedation in
      young children MET-PET studies should be restricted to this group of patients
      when a decision for further therapy is not possible from routine diagnostic
      procedures alone, e.g., structural imaging. We investigated the diagnostic
      accuracy of MET-PET for the differentiation between tumorous and non-tumorous
      lesions in this group of patients. Forty eight MET-PET scans from 39 patients
      aged from 2 to 21 years (mean 15 +/- 5.0 years) were analyzed. The MET tumor
      uptake relative to a corresponding control region was calculated. A receiver
      operating characteristic (ROC) was performed to determine the MET-uptake value
      that best distinguishes tumorous from non-tumorous brain lesions. A
      differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9)
      was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of
      83% and a specificity of 92%, respectively. A differentiation between high grade
      malignant lesions (mean MET-uptake = 2.00 +/- 0.46) and low grade tumors (mean
      MET-uptake = 1.84 +/- 0.31) was not possible. There was a significant difference
      in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO
      grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a
      useful tool to differentiate tumorous from non-tumorous lesions in children and
      young adults when a decision for further therapy is difficult or impossible from
      routine structural imaging procedures alone.

PMID- 19575149
TI  - Intraventricular gliosarcoma: unusual location of an uncommon tumor.
AB  - Gliosarcomas are uncommon variants of glioblastoma bearing the histological
      hallmark of two distinct tumor components (high grade glial and sarcomatous).
      They share similarities with glioblastomas as far as clinico-epidemiological and
      prognostic factors are concerned. They are commonly cortically-surfacing lesions
      occurring mostly in the supratentorial compartment. Intraventricular location of
      a gliosarcoma is very uncommon and reported only once before. We report one such
      case where the lesion was subependymal and protruded into the ventricle giving
      the appearance of a truly intraventricluar tumor. We discuss this case and review
      the relevant literature.

PMID- 19575150
TI  - Intradural clival chordoma: a rare pathological entity.
AB  - Chordomas constitute about 1% of intracranial tumors. They are generally
      extradural destroying the bone. Intradural chordomas are very rare. We present
      one such case of a clival intradural chordoma who presented with a left
      trigeminal nerve sensory neuropathy. The lesion was totally excised uneventfully
      via a retromastoid suboccipital approach. There was no recurrence of the lesion
      at 1-year follow-up. Characteristics of intradural chordoma and its close
      differential ecchordosis physaliphora are reviewed in this article.

PMID- 19575151
TI  - Principles of the therapy of bone infections in adult extremities : Are there any
      new developments?
AB  - Septic diseases of the bone and immediately surrounding soft tissues can be
      differentiated into osteitis or osteomyelitis. Both are a most serious diagnosis
      in modern traumatology and orthopaedic surgery. The basis for treatment is a
      highly specific, problem-adapted therapy with a defined strategy, the paramount
      goal being to preserve the stable weightbearing bones, maintain a good mechanical
      axis with correctly working muscles and joints, and avoid permanent disability.
      "State-of-the-art" therapy of osteitis and osteomyelitis has two priorities: (a)
      Eradication of the infection; (b) Reconstruction of bone and soft tissue.
      Surgical treatment with resection of the affected bone segments and soft tissue,
      followed by reconstructive methods continues to be the main basic therapy, and is
      supported by local and systemic antibiotics and adjuvant methods such as
      hyperbaric oxygen. This article provides an overview of the diagnostic features
      and different surgical procedures as well as the current literature in order to
      reach the above named goals.

PMID- 19575152
TI  - Effect of chain length of alcohol on the lipase-catalyzed esterification of
      propionic acid in supercritical carbon dioxide.
AB  - The esterification of propionic acid was investigated using three different
      alcohols, namely, isopropyl alcohol, isobutyl alcohol, and isoamyl alcohol. The
      variation of conversion with time for the synthesis of isoamyl propionate was
      investigated in the presence of five enzymes. Novozym 435 showed the highest
      activity, and this was used as the enzyme for investigating the various
      parameters that influence the esterification reaction. The Ping-Pong Bi-Bi model
      with inhibition by both acid and alcohol was used to model the experimental data
      and determine the kinetics of the esterification reaction.

PMID- 19575153
TI  - Response surface methodology-based optimisation of agarose gel electrophoresis
      for screening and electropherotyping of rotavirus.
AB  - Management of rotavirus diarrhoea cases and prevention of nosocomial infection
      require rapid diagnostic method at the patient care level. Diagnostic tests
      currently available are not routinely used due to economic or
      sensitivity/specificity constraints. Agarose-based sieving media and running
      conditions were modulated by using central composite design and response surface
      methodology for screening and electropherotyping of rotaviruses. The
      electrophoretic resolution of rotavirus genome was calculated from input
      parameters characterising the gel matrix structure and running conditions.
      Resolution of rotavirus genome was calculated by densitometric analysis of the
      gel. The parameters at critical values were able to resolve 11 segmented
      rotavirus genome. Better resolution and electropherotypic variation in 11
      segmented double-stranded RNA genome of rotavirus was detected at 1.96% (w/v)
      agarose concentration, 0.073 mol l(-1) ionic strength of Tris base-boric acid
      ethylenediamine tetraacetic acid buffer (1.4x) and 4.31 h of electrophoresis at
      4.6 V cm(-1) electric field strength. Modified agarose gel electrophoresis can
      replace other methods as a simplified alternative for routine detection of
      rotavirus where it is not in practice.

PMID- 19575154
TI  - Infectious aspects and the etiopathogenesis of rheumatoid arthritis.
AB  - Infections are believed to contribute to the maturation of the immune system from
      the innate to the adaptive phases and therefore may take part in the induction of
      autoimmune conditions. In the current study, we present an extensive analysis
      conducted on sera samples of patients with rheumatoid arthritis in order to seek
      evidence of previous or coexisting infectious processes using the Bio-Rad BioPlex
      immunoassay analyzer. We detected higher rates of serological evidence of
      infections with Epstein-Barr virus and cytomegalovirus viruses. Our findings may
      indicate a role of these viruses in the pathogenesis of RA.

PMID- 19575155
TI  - Sports and sudden death.

PMID- 19575156
TI  - Sudden cardiac death in athletes: can it be prevented by screening?
AB  - In 1982, a nationwide program of preparticipation screening of all individuals
      embarking in competitive sports activity was launched in Italy. The screening
      protocol includes athlete's personal and family history, physical examination,
      and twelve-lead electrocardiogram (ECG) as first-line examination; additional
      tests such as echocardiography or exercise testing are requested only for
      subjects who have positive findings at the initial evaluation. This screening
      algorithm, which has been used for preparticipation evaluation of millions of
      Italian athletes over a period of > 25 years has provided adequate sensitivity
      and specificity for detection of athletes affected by potentially dangerous
      cardiomyopathy or arrhythmia at risk of athletic-field death and has led to
      substantial reduction of mortality of young competitive athletes (by
      approximately 90%), mostly by preventing sudden death from cardiomyopathy.

PMID- 19575157
TI  - Congenital anomalies of coronary arteries: role in the pathogenesis of sudden
      cardiac death.
AB  - After hypertrophic cardiomyopathy, coronary artery anomalies of origin from the
      wrong sinus of Valsalva are the second most common cause of sudden death on the
      athletic field in the USA. Although the right coronary artery arising from the
      left coronary sinus (ARCA) is four times as common as the left coronary artery
      arising from the anterior sinus (ALCA), it is the latter that is by far the more
      common cause of sudden death with or shortly after vigorous physical activity. Of
      the four types of ALCA, the interarterial type, where the left coronary artery
      passes anteriorly between the aorta and the right ventricular outflow tract, is
      the only type that places the patient at risk of sudden death. Another feature of
      this syndrome is the fact that sudden death occurs associated with or shortly
      after vigorous exercise and is very unusual after the patient is > 35 years of
      age. The mechanism by which there is sudden occlusion of the interarterial
      coronary artery is at present unknown, although there are a number of hypotheses
      involving the oblique passage of the vessel as it leaves the aorta. Sudden death
      is probably rare considering the number of people who have these anomalies.
      Symptoms premonitory to a fatal event such as exertional syncope, chest pain, or
      palpitations are probably common in patients at risk, and surgical correction is
      indicated in symptomatic patients at any age. In older asymptomatic patients,
      surgery is not recommended, since the incidence of sudden death in this age group
      is extremely small. In asymptomatic young patients, a stress test, preferably
      with radioisotope myocardial perfusion imaging or stress echocardiogram, should
      be done and surgical correction performed in those with ischemia provoked in the
      appropriate myocardial region. Since there is evidence that in patients who have
      survived a potentially fatal event, it is rare to be able to provoke ischemia
      with equal or greater exercise than had precipitated the malignant arrhythmia,
      the decision to surgically correct an asymptomatic young patient, serendipitously
      found to have ALCA, who has a negative exercise test, is debatable. Any decision
      for surgery in such patients should be made only after a full discussion of the
      risks pro and con surgery with the patient and the patient's family.

PMID- 19575158
TI  - Channelopathies: Brugada syndrome, long QT syndrome, short QT syndrome, and CPVT.
AB  - In approximately 10-20% of all sudden deaths, no structural cardiac abnormalities
      can be identified. Important potential causes of sudden cardiac deaths in the
      absence of heart disease are primary electrical diseases such as Brugada
      syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and
      catecholaminergic polymorphic ventricular tachyarrhythmias (CPVT). The resting
      ECG and the ECG under exercise are pivotal for the diagnosis of ion channel
      diseases. Molecular genetic screening can reveal underlying mutations in a
      variable degree among the cardiac ion channel diseases in up to 70% (LQTS) and
      may identify individuals with incomplete penetration of the disease. In patients
      with primary electrical diseases, specific clinical triggers for arrhythmic
      events such as syncope or sudden cardiac death have been identified including
      exercise, strenuous activity, auditory stimuli, or increased vagal tone. Young,
      otherwise healthy individuals are likely to be involved in sports activity.
      Therefore, special attention has to be given to advise these patients.
      Competitive sports and vigorous exercise are contraindications in almost all
      patients. Even recreational exercise may have to be avoided in phenotypically
      overt patients or silent gene carriers depending on the underlying disease.

PMID- 19575159
TI  - Arrhythmogenic right ventricular cardiomyopathy: diagnosis and risk
      stratification.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVCM) is a genetically
      determined disease characterized by the progressive replacement of cardiomyocytes
      by fibrofatty tissue, predominantly in the right ventricle. It leads to
      electrical instability and is therefore a major cause of sudden cardiac death
      (SCD) in apparently healthy young individuals, particularly in athletes. The
      diagnosis of ARVCM can be challenging and is based on a set of major and minor
      criteria which include structural, functional, histological, imaging,
      electrocardiographic and anamnestic parameters. ARVCM can be diagnosed, when two
      major criteria, or one major and two minor criteria, or four minor criteria from
      different categories are present. An implantable cardioverter defibrillator (ICD)
      should be used in patients who were resuscitated from SCD or who present with
      sustained ventricular tachycardia or otherwise unexplained syncope. The role of
      ICD therapy in primary prevention of SCD is a matter of ongoing debate and has to
      be decided on an individualized basis. Due to the familial accumulation of the
      disease, the screening of relatives is important. For the symptomatic treatment
      of arrhythmias, beta-blockers, sotalol, amiodarone and catheter ablation can be
      used. Arrhythmias in patients with ARVCM often occur in conjunction with physical
      exercise. Patients with ARVCM should therefore abstain from competitive sports or
      leisure-time activities where any possible loss of consciousness poses an
      increased hazard (scuba diving, hang gliding, parachuting, etc.).

PMID- 19575161
TI  - [Myocarditis and sudden cardiac death in athletes. Diagnosis, treatment, and
      prevention].
AB  - Myocarditis is the reason for sudden cardiac death in 5-22% of athletes < 35
      years of age. Actually, parvovirus B19 and human herpes virus 6 are the most
      important pathogens. Clinical presentation of myocarditis is heterogeneous, with
      all courses between asymptomatic and fulminant reported. Especially in athletes
      it is important to take subtle discomforts seriously and initiate further
      evaluation. Electrocardiogram, laboratory parameters, serologic markers, and
      echocardiography are helpful in diagnosis of myocarditis, but are not specific.
      Magnetic resonance imaging (MRI) of the heart has become an important tool in the
      evaluation of patients with myocarditis and allows noninvasive appraisal of
      myocardial inflammation using late enhancement. However, MRI is not able to
      assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold
      standard in diagnosis of myocarditis. When considering EMB in these athletes one
      should not ignore spontaneous healing in 50% of patients with myocarditis.
      Contrariwise, specific therapy (e.g., immunosuppression, interferon,
      immunoglobulins) for myocarditis is only feasible after getting results of EMB.
      When myocarditis is verified, athletes have to withdraw from sport for at least 6
      months. Before restarting physical activity, a detailed examination is necessary
      and most of the patients will undergo another EMB. For prevention of myocarditis
      and sudden cardiac death it is recommended to stop elite sport for 4 weeks after
      an unspecific infection. Whether moderate sport can be started earlier is
      unclear.

PMID- 19575162
TI  - Hypertrophic cardiomyopathy as a cause of sudden death.
AB  - Hypertrophic cardiomyopathy (HCM) is the main cause of sudden unexpected death in
      the young and especially in young athletes with an incidence up to 2.3 per
      100,000 athletes and year. Risk stratification models including patient history
      (syncope, familial risk of sudden death) and findings in noninvasive tests
      (nonsustained ventricular tachycardia, abnormal blood pressure response during
      exercise, maximum left ventricular wall thickness > or = 30 mm) have been
      developed in order to estimate the risk of individual patients. Echocardiographic
      parameters are helpful in distinguishing HCM from athlete's heart. Definitive
      diagnosis of HCM implicates disqualification from competitive sports resulting in
      a significant reduction of sudden cardiac death due to HCM during sports
      competition. This positive development should lead to a widespread
      preparticipation screening of athletes including historical, clinical, and
      electrocardiographic examination. At least in borderline findings and symptomatic
      athletes, an additional echocardiogram should be performed in order to minimize
      or better exclude the risk of sudden cardiac death.

PMID- 19575163
TI  - [Palpitations in competitive athletes. Risks from premature beats, nonsustained
      tachycardia and preexcitation].
AB  - Cardiovascular screening tests to prevent sudden cardiac death in athletes are
      discussed controversially, but they should include diligent patient history and
      physical examination as well as registration of an ECG. If palpitations or
      tachycardias are described or if preexcitation, supraventricular or ventricular
      arrhythmias are documented, further risk stratification is mandatory.
      Specifically the origin and the complexity of the arrhythmia need to be analyzed
      and any form of structural cardiac pathologies has to be ruled out. Sinus
      tachycardia, supraventricular and ventricular premature beats, atrial
      fibrillation as well as supraventricular and ventricular tachycardia may serve as
      substrate for palpitations. Each of these arrhythmias is associated with a
      different amount of cardiac risk and can be evidence for certain forms of
      structural cardiac disease. Recommendations to limit physical activity and
      specific treatment options depend on the type of the arrhythmia and the presence
      and the nature of underlying cardiac disease.

PMID- 19575164
TI  - [Cardiac memory of the ECG following ventricular pacing].
AB  - During abnormal pacemaker depolarization, abnormal repolarization occurs and
      persists in normal QRS beats often seen in alternation with paced beats. The T
      wave direction of normal beats is typically similar to the direction of the QRS
      complex during pacing, hence the term cardiac memory. The normal nonpaced beats
      have shown a sensitivity of 92% and a specificity of 100% for cardiac memory in
      the presence of T-wave inversions (TWI) in the precordial and inferior (II, III
      and aVF) leads with a positive T wave in aVL, a positive or isoelectric T wave in
      lead I, and the maximal precordial TWI being greater than the TWI of lead III,
      discriminating it from ischemic precordial TWI. In the latter, TWI are also seen
      in leads aVL and I.

PMID- 19575165
TI  - Image of the month. Brugada-like ECG pattern in a patient with isolated right
      ventricular infarction.

PMID- 19575167
TI  - [Peridural anaesthesia with ropivacaine for a patient with Friedrich's ataxia.
      Caesarean section after dorsal stabilisation of the spinal column (Th5-L1)].
AB  - Friedreich's ataxia (FA) is a hereditary disease, which leads to degenerative
      changes in the spinal cord and cerebellum (incidence 1:50,000). These changes are
      caused by a defect in the gene that encodes a mitochondrial gene called frataxin
      and causes muscle weakness, scoliosis, cardiomyopathy and impaired glucose
      tolerance. Therefore, these patients require special care during anaesthesia. We
      report the case of a 25-year-old primigravida with a history of FA and dorsal
      stabilisation of the vertebral column, who was admitted to our hospital for
      elective caesarean section. Due to increased sensitivity to muscle relaxants,
      peridural anaesthesia with 8 ml 0.75% ropivacaine and 10 microg sufentanil was
      used in this case. The perioperative neurological consultation revealed no undue
      exacerbation of symptoms.

PMID- 19575168
TI  - [Fast track in casualty surgery].
AB  - The concept of "fast track" has not yet been established in orthopaedic trauma
      surgery. Principles such as those used in the "fast track" procedure for
      abdominal surgery have been employed in orthopaedic surgery for a long time. The
      best results can be achieved by early operative treatment, stable osteosynthesis
      and, if the soft tissues allow, an early initiation of mobilization under optimal
      pain management. Based on new techniques in osteosynthesis, in particular locked
      screw techniques, "fast track" is also applicable for fragility fractures
      (osteoporosis), complex shattered bone and bone defect situations.

PMID- 19575169
TI  - [Circulatory disorders of the renal and mesenteric arteries].
AB  - Symptomatic mesenteric circulatory disorders are potentially life-threatening
      diseases with an increasing frequency due to the demographic population
      development. Renal artery stenosis is a well accepted cause of hypertension or at
      least deterioration of blood pressure control as well as the cause of a
      progressive course of renal insufficiency if of an atherosclerotic nature.
      Further consequences of renal artery stenosis, such as left ventricle hypertrophy
      and hypertensive encephalopathy are topics of recent research. Due to progress in
      percutaneous techniques during the last decade interventional therapy has
      replaced surgery as the treatment method of choice for lesions located near the
      origin. The only randomized study comparing endovascular stent revascularization
      with best medical therapy (ASTRAL) failed to show a benefit of revascularization
      of renal artery stenoses.

PMID- 19575170
TI  - [Peripheral arterial disease: secondary prevention, medical therapy,
      revascularization].
AB  - Patients with peripheral arterial disease have a high risk of cardiovascular
      morbidity and mortality. Thus, antiplatelet drugs, antidiabetic, antihypertensive
      and antilipemic agents should be administered early on. Smoking cessation has to
      be encouraged and supported. In case of significant reduction of walking distance
      with impaired quality of life structured and supervised exercise training as well
      as vasoactive substances have to be offered. If technically feasible and
      critically discussed with the patient revascularization procedures of the aorto
      iliac and the femoro-popliteal segment may be performed. In patients with
      critical limb ischemia, all options for vascularisation have to be utilized as
      the main goal is limb salvage. As medication, only prostanoids have to be
      considered.

PMID- 19575171
TI  - [Interstitial lung diseases and pulmonary hypertension].
AB  - The prevalence of pulmonary hypertension in interstitial lung disease (ILD) is
      high (30-40%). However, diagnosis of pulmonary hypertension in ILD is often
      delayed. Pulmonary hypertension can occur in the absence of advanced pulmonary
      dysfunction or severe hypoxia and is associated with a worse prognosis. A number
      of pathogenic mechanisms such as oxidative stress, cytokines, and the endothelin
      system have been implicated in remodeling of both the lung parenchyma and the
      vessels. In addition, hypoxic vasoconstriction, vascular destruction and
      progressive fibrosis play an important role. Since clinical signs are often non
      specific echocardiography, radiology and laboratory parameters such as NT-proBNP
      may be helpful. However, the definitive diagnosis of pulmonary hypertension is
      still confirmed by right heart catheterization. Treatment options of pulmonary
      hypertension in ILD are limited to the treatment of the underlying diseases.
      Newer vasodilating drugs may improve the prognosis but have first to be evaluated
      in clinical trials. Lung or lung and heart transplantation is the therapeutic
      option in end stage disease.

PMID- 19575172
TI  - [Obstructive pulmonary diseases and pulmonary hypertension].
AB  - Pulmonary hypertension is a frequent complication of chronic obstructive
      pulmonary disease. Especially in patients with concurrent sleep apnoe syndrome
      (so called "overlap syndrome"), the risk for pulmonary hypertension is high.
      Pathophysiologically, both toxic effects (cigarette smoke) and alveolar
      hypoventilation can induce dysfunction of the pulmonary endothelium. Genetic
      factors and cytokines/growth factors released by inflammatory cells may induce
      remodeling of the pulmonary vessels. Pulmonary hypertension results, which is
      initially reversible, but gradually worsens over time. At present, therapeutic
      options include long term oxygen in addition to the treatment of the underlying
      disease. A subgroup of patients may profit of a specific therapy with sildenafil
      and other new substances. However, studies that define these subgroups need to be
      performed.

PMID- 19575173
TI  - Elevated circulating levels of matrix metalloproteinases MMP-2 and MMP-9 in
      pseudoxanthoma elasticum patients.
AB  - Pseudoxanthoma elasticum (PXE) is a rare disorder predominantly affecting the
      skin, the eyes, and the cardiovascular system. The disease is caused by mutations
      in the ABCC6 gene and characterized by ectopic calcification and extracellular
      matrix (ECM) alterations. Matrix metalloproteinases (MMPs) play a pivotal role in
      the process of ECM remodeling. In the present study, we investigated matrix
      metalloproteinases MMP-2 and MMP-9 in PXE patients compared to healthy controls.
      We analyzed the serum concentrations of MMP-2 and MMP-9 in a cohort of 69 German
      PXE patients and in 69 healthy, age-, and sex-matched control subjects using
      commercially available ELISA assays. We found elevated concentrations of both
      MMPs in the sera of PXE patients. MMP-2 levels were significantly higher in
      patients than controls (231 +/- 5.89 vs 202 +/- 5.17 ng/ml, p = 0.0002), as were
      MMP-9 levels (841 +/- 65.9 vs 350 +/- 30.8 ng/ml, p < 0.0001). Our findings point
      to an involvement of matrix metalloproteinases in PXE pathology. ECM remodeling
      in PXE is reflected by elevated levels of circulating MMP-2 and MMP-9. Those MMPs
      might, therefore, be applicable as serum markers for the matrix-degradative
      process in PXE.

PMID- 19575174
TI  - [Fractures of the shaft of the femur].
AB  - The femur is the largest, longest and strongest bone in the human skeleton.
      Fractures of the shaft of the femur can result from high energy as well as low
      energy trauma and 30% of patients have multiple injuries. In the clinical
      diagnostic special attention must be paid to the peripheral neurovascular status
      as well as the possibility of a compartment syndrome. Fractures of the femur
      shaft are defined according to the AO classification. Treatment is as a rule
      operative, except for children up the end of 4 years old. Medullary nailing is
      nowadays the method of choice and the nails can be implanted in an anterograde or
      retrograde direction. The introduction of nails after boring out the medullar is
      associated with an increased healing rate in comparison to non-boring techniques.
      Various techniques are available for the often promising method of repositioning
      and the intraoperative controls. Plating is reserved only for special situations.
      External fixation is of great value in adults for temporary fixation of fractures
      of the femur shaft. Full weight bearing is possible immediately following the
      operation depending on the type of fracture and method of treatment.
      Uncomplicated fracture healing does not result in a reduction in the ability to
      work. Despite the generally good prognosis and improvement in design and
      technology of implants, fractures of the femur shaft still represent a special
      challenge for the treating casualty surgeon.

PMID- 19575175
TI  - Melanin-based coloration covaries with ovary size in an age-specific manner in
      the barn owl.
AB  - While the adaptive function of black eumelanin-based coloration is relatively
      well known, the function of reddish-brown pheomelanin-based coloration is still
      unclear. Only a few studies have shown or suggested that the degree of reddish
      brownness is associated with predator-prey relationships, reproductive
      parameters, growth rate and immunity. To gain insight into the physiological
      correlates of melanin-based coloration, I collected barn owl (Tyto alba) cadavers
      and examined the covariation between this colour trait and ovary size, an organ
      that increases in size before reproduction. A relationship is expected because
      melanin-based coloration often co-varies with sexual activity. The results showed
      that reddish-brown juveniles had larger ovaries than whiter juveniles
      particularly in individuals in poor condition and outside the breeding season,
      while in birds older than 2 years lightly coloured females had larger ovaries
      than reddish-brown conspecifics. As barn owls become less reddish-brown between
      the first and second year of age, the present study suggests that reddish-brown
      pheomelanic and whitish colorations are associated with juvenile- and adult
      specific adaptations, respectively.

PMID- 19575176
TI  - [Leadership and talent initiatives in urology].
AB  - Over the past 2 years the majority of clinics in Germany had problems to find
      qualified personnel. This was the conclusion of a study by the Victoria Life
      Insurance and the FAZ Institute. The investigation was based on a survey of those
      responsible for personnel decisions in large business concerns and clinics in
      Germany. The main topics of the interviews were the insufficient professional
      perspectives, inadequate financial resources, family unfriendly working hours and
      continuously growing bureaucracy.

PMID- 19575177
TI  - Severe hypoglycaemia and cognitive impairment in older patients with diabetes:
      the Fremantle Diabetes Study.
AB  - AIMS/HYPOTHESIS: The aim was to investigate the relationship between severe
      hypoglycaemia and cognitive impairment in older patients with diabetes. METHODS:
      A sample of 302 diabetic patients aged >/=70 years was assessed for dementia or
      cognitive impairment without dementia in 2001-2002 and a subsample of non
      demented patients (n = 205) was followed to assess cognitive decline. A history
      of severe hypoglycaemia was determined from self-reports, physician assessments
      and records of health service use for hypoglycaemia (HSH). Prospective HSH was
      determined up to 2006. Data analysis, including multiple logistic and Cox
      regression models, was used to determine whether: (1) there were cross-sectional
      associations between hypoglycaemia and cognitive status, (2) historical
      hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status
      predicted subsequent HSH. RESULTS: There were significant cross-sectional
      associations between both cognitive impairment and dementia and hypoglycaemia.
      Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95%
      CI 1.06-8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI
      1.43-12.13). However, there were no significant associations between historical
      hypoglycaemia, incident HSH and cognitive decline. CONCLUSIONS/INTERPRETATION:
      Dementia is an important risk factor for hypoglycaemia requiring health service
      utilisation. We found no evidence that hypoglycaemia contributes to cognitive
      impairment in older patients with diabetes.

PMID- 19575178
TI  - Maggot secretions suppress pro-inflammatory responses of human monocytes through
      elevation of cyclic AMP.
AB  - AIMS/HYPOTHESIS: Maggots of the blowfly Lucilia sericata are used for the
      treatment of chronic wounds. As monocytes may contribute to the excessive
      inflammatory responses in such wounds, this study focussed on the effects of
      maggot secretions on the pro-inflammatory activities of these cells. METHODS:
      Freshly isolated monocytes were incubated with a range of secretions for 1 h and
      then stimulated with lipopolysaccharides (range 0-100 ng/ml) or lipoteichoic acid
      (range 0-5 microg/ml) for 18 h. The expression of cell surface molecules,
      cytokine and chemokine levels in culture supernatants, cell viability,
      chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured.
      RESULTS: Maggot secretions dose-dependently inhibited production of the pro
      inflammatory cytokines TNF-alpha, IL-12p40 and macrophage migration inhibitory
      factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while
      enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell
      surface receptors involved in pathogen recognition remained unaffected by
      secretions. In addition, maggot secretions altered the chemokine profile of
      monocytes by downregulating macrophage inflammatory protein-1beta and
      upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless,
      chemotactic responses of monocytes were inhibited by secretions. Furthermore,
      maggot secretions did not affect phagocytosis and intracellular killing of S.
      aureus by human monocytes. Finally, secretions induced a transient rise in the
      intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited
      the effects of secretions. CONCLUSIONS/INTERPRETATION: Maggot secretions inhibit
      the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent
      mechanism. Regulation of the inflammatory processes by maggots contributes to
      their beneficial effects on chronic wounds.

PMID- 19575179
TI  - Etiologies and outcome of acute respiratory failure in HIV-infected patients.
AB  - OBJECTIVE: To assess the etiologies and outcome of acute respiratory failure
      (ARF) in HIV-infected patients over the first decade of combination
      antiretroviral therapy (ART) use. METHODS: Retrospective study of all HIV
      infected patients (n = 147) admitted to a single intensive care unit (ICU) for
      ARF between 1996 and 2006. RESULTS: ARF revealed the diagnosis of HIV infection
      in 43 (29.2%) patients. Causes of ARF were bacterial pneumonia (n = 74),
      Pneumocystis jirovecii pneumonia (PCP, n = 52), other opportunistic infections (n
      = 19), and noninfectious pulmonary disease (n = 33); the distribution of causes
      did not change over the 10-year study period. Two or more causes were identified
      in 33 patients. The 43 patients on ART more frequently had bacterial pneumonia
      and less frequently had opportunistic infections (P = 0.02). Noninvasive
      ventilation was needed in 49 patients and endotracheal intubation in 42. Hospital
      mortality was 19.7%. Factors independently associated with mortality were
      mechanical ventilation [odds ratio (OR) = 8.48, P < 0.0001], vasopressor use (OR,
      4.48; P = 0.03), time from hospital admission to ICU admission (OR, 1.05 per day;
      P = 0.01), and number of causes (OR, 3.19; P = 0.02). HIV-related variables (CD4
      count, viral load, and ART) were not associated with mortality. CONCLUSION:
      Bacterial pneumonia and PCP remain the leading causes of ARF in HIV-infected
      patients in the ART era. Hospital survival has improved, and depends on the
      extent of organ dysfunction rather than on HIV-related characteristics.

PMID- 19575180
TI  - Knee laxity measurements after anterior cruciate ligament reconstruction, using
      either bone-patellar-tendon-bone or hamstring tendon autografts, with special
      emphasis on comparison over time.
AB  - The aims of the study were to analyse the change in knee laxity over time after
      anterior cruciate ligament (ACL) reconstruction, using either bone-patellar
      tendon-bone (BPTB) or hamstring (HS) tendon autografts, and to compare the knee
      laxity measurements between the study groups both pre-operatively and on multiple
      follow-up occasions. Another aim was to compare the radiographic findings in
      terms of degenerative changes between the study groups. A randomised series of 71
      patients, who underwent ACL reconstruction using BPTB or HS tendon autografts and
      interference screw fixation, were included in the study. Of these patients, 47/71
      (66%) attended a clinical examination, including laxity measurements using the KT
      1000 arthrometer, pre-operatively and on four post-operative occasions; 6 months,
      1 year, 2 years and 7 years after the reconstruction. The BPTB group consisted of
      22 patients, while there were 25 patients in the HS group. There were no
      significant differences in the mean side-to-side knee laxity between the BPTB and
      the HS group pre-operatively or at the follow-up examinations. There was a
      tendency towards a reduction in side-to-side knee laxity over time in both
      groups, measured with the KT-1000 arthrometer. The decrease was significant when
      analysing the injured and uninjured knee separately (injured side p < 0.001
      (BPTB) and p = 0.005 (HS), uninjured side p = 0.008 and p = 0.042, respectively).
      Forty-four patients (BPTB 21, ST 23) underwent a radiographic assessment at the 7
      year follow-up, which revealed no significant differences between the study
      groups in terms of osteoarthritic findings classified according to the Fairbank
      and Ahlback rating systems. In overall terms, osteoarthritis was identified in
      16% (BPTB 19%; ST 13%; n.s.) according to the Ahlback rating system and 68% (BPTB
      67%; ST 70%; n.s.) according to the Fairbank rating system. There were no
      significant differences in knee laxity measurements between the two study groups
      pre-operatively or at 7 years. A decrease in knee laxity over time was seen in
      both groups. There were no significant differences between the BPTB and ST groups
      in terms of osteoarthritic findings at 7 years.

PMID- 19575181
TI  - Physiological anterior laxity in healthy young females: the effect of knee
      hyperextension and dominance.
AB  - Female athletes are more likely to sustain an anterior cruciate ligament (ACL)
      injury. Knee laxity, hyperextension and limb dominance have been suggested as
      possible factors contributing to the knee injury. The aims of this study were to
      investigate the physiological anterior knee laxity between the dominant and non
      dominant limb and in healthy young females with and without hyperextension knees.
      Forty-two healthy young females, 21 with hyperextension knees, were recruited
      voluntarily for this study. The subjects were tested with KT-2000 knee ligament
      arthrometer at both knees with flexion 30 degrees to obtain the anterior tibial
      displacements at loadings of 45, 67, 89 and 134 N. The initial and terminal
      stiffnesses were further calculated and analyzed to demonstrate the differences
      in the characteristics of knee laxity between limbs and groups. The results
      showed that there was no significant displacement difference between
      hyperextension and non-hyperextension groups. However, different physiological
      anterior laxities were illustrated for the different limbs and groups. The non
      dominant side of the hyperextension group had significantly smaller terminal
      stiffness than that of the non-hyperextension group. The dominant side of the
      hyperextension group had larger laxity than the non-dominant side in the higher
      loading conditions. These findings may explain hyperextension knees are at
      greater risk of sustaining an ACL injury.

PMID- 19575182
TI  - Covalent binding of organophosphorothioates to albumin: a new perspective for OP
      pesticide biomonitoring?
AB  - We here report on the covalent binding of various organophosphorothioate (OPT)
      pesticides to albumin at in vitro exposure levels that did not give rise to
      butyrylcholinesterase inhibition. Adduct formation occurred at the Tyr-411
      residue of albumin, as was firmly corroborated by LC-tandem MS analysis of a
      pepsin digest of OPT-modified albumin. It cannot be excluded that other
      (tyrosine) residues become modified as well. A convenient method for mass
      spectrometric determination of the OPT tyrosine adduct has also been developed
      based on the pronase digestion of albumin and subsequent LC-tandem MS analysis of
      the digest. The resulting tyrosine phosphorothioate ester displayed favorable
      chromatographic and mass spectrometric properties for sensitive analysis. In
      vitro exposure levels of parathion and chlorpyrifos down to 1 microM could
      readily be assessed. The remarkable affinity of OPTs for albumin opens the way
      for a more complete assessment of OP pesticide exposure.

PMID- 19575183
TI  - Effects of quetiapine on monoamine, GABA, and glutamate release in rat prefrontal
      cortex.
AB  - INTRODUCTION: The atypical antipsychotic drug, quetiapine (QTP), is effective in
      schizophrenia and mood disorders, but induces seizures compared to typical
      antipsychotics. METHODS: To explore the mechanisms of action of QTP, we
      determined its effects on extracellular levels of norepinephrine, dopamine,
      serotonin, gamma-aminobutyric acid (GABA), and glutamate in the medial prefrontal
      cortex (mPFC) using microdialysis, and neuronal firing in the ventral tegmental
      area (VTA), locus coeruleus (LC), dorsal raphe nucleus (DRN), and mediodorsal
      thalamic nucleus (MTN) by telemetry in freely moving rats. RESULTS: QTP (10 and
      30 mg/kg, i.p.) activated neuronal firing in the VTA, LC, and MTN without
      affecting that in the DRN. QTP increased extracellular levels of norepinephrine,
      dopamine, and glutamate without affecting serotonin or GABA levels in the mPFC.
      The stimulatory effects of QTP on norepinephrine and dopamine were mediated by
      positive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)/glutamatergic and negative GABA-mediated NMDA/glutamatergic regulation.
      DISCUSSION: The dopaminergic terminal projecting from the VTA received inhibitory
      GABA-mediated NMDA/glutamatergic regulation, but not stimulatory
      AMPA/glutamatergic regulation. However, both dopaminergic and noradrenergic
      terminals from the LC received stimulatory AMPA/glutamatergic regulation from the
      MTN, but not inhibitory GABA-mediated NMDA/glutamatergic regulation. These
      findings correlating neuronal activities in nuclei with neurotransmitter release
      suggested that the effects of QTP on neurotransmission in the mPFC depend on
      activated neuronal projections located outside the mPFC. Furthermore, positive
      interaction between LC and MTN afferents are potentially important in the
      pharmacological mechanisms of neurotransmitter regulation by QTP and hint at
      mechanisms underlying the atypical profile of this drug for treatment of
      schizophrenia and as a mood stabilizer and proconvulsive agent.

PMID- 19575184
TI  - Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB
      334867, disrupts attentional performance in rats.
AB  - RATIONALE: Orexin neurons project to a number of brain regions, including onto
      basal forebrain cholinergic neurons. Basal forebrain corticopetal cholinergic
      neurons are known to be necessary for normal attentional performance. Thus, the
      orexin system may contribute to attentional processing. OBJECTIVES: We tested
      whether blockade of orexin-1 receptors would disrupt attentional performance.
      METHODS: Rats were trained in a two-lever sustained attention task that required
      discrimination of a visual signal (500, 100, 25 ms) from trials with no signal
      presentation. Rats received systemic or intrabasalis administration of the orexin
      1 receptor antagonist, SB-334867, prior to task performance. RESULTS: Systemic
      administration of the orexin-1 receptor antagonist, SB-334867 (5.0 mg/kg),
      decreased detection of the longest duration signal. Intrabasalis SB-334867 (0.60
      microg) decreased overall accuracy on trials with longer signal durations.
      CONCLUSIONS: These findings suggest that orexins contribute to attentional
      processing, although neural circuits outside of basal forebrain corticopetal
      cholinergic neurons may mediate some of these effects.

PMID- 19575185
TI  - Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake,
      body weight change, and pruritus in rats.
AB  - RATIONALE: The cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has
      been shown to decrease body weight in laboratory animals and humans. Furthermore,
      SR141716A can elicit scratching behavior in rodents, a behavior that has been
      hypothesized to contribute to SR141716A-induced decrease in food intake. Although
      childhood obesity is a rising health issue, it is unknown whether SR141716A is
      equipotent at modulating food intake and other CB1-mediated behaviors in younger
      subjects. OBJECTIVE: To determine whether CB1 receptor blockade is equipotent at
      modulating food and water intake, body weight, and scratching behavior, the
      effect of a range of SR141716A doses on these behaviors in food-restricted
      postnatal day (P) 18, 28, and 60 male rats was investigated. Brain concentrations
      of SR141716A were determined in each age group. RESULTS: SR141716A dose- and age
      dependently suppressed food and water intake and body weight gain and elicited
      head scratching, with the most potent effects observed in P18 and P28 rats. Brain
      concentrations of SR141716A were significantly elevated in P18 rats relative to
      P28 and P60 rats. SR141716A-elicited head scratching was attenuated by the 5
      HT(2A/2C) antagonist ketanserin. CONCLUSIONS: SR141716A is more potent at
      modulating food intake and head scratching in very young animals; these
      differences can be attributed to an increase in brain penetration of SR141716A
      for P18 but not for P28 and P60 rats. In addition, SR141716-elicited head
      scratching is modulated by 5HT receptor antagonism and is not a contributing
      factor to SR141716A's anorectic effects.

PMID- 19575186
TI  - Selection of SPE cartridge for automated solid-phase extraction of pesticides
      from water followed by liquid chromatography-tandem mass spectrometry.
AB  - In environmental analyses there is an ever-increasing need to develop simple and
      sensitive multi-residue methods. In many agricultural regions, there is
      particular concern of the potential for pesticides to enter rivers and other
      waterways. This study reports on the development and validation of a multi
      residue method of analysis for 30 pesticides in water samples using solid-phase
      extraction (SPE) followed by LC-MS/MS. The electrospray and MS/MS parameters were
      optimised for each pesticide, including capillary voltage, collision-induced
      dissociation voltage, and selection of a precursor ion and two product ions. A
      variety of SPE sorbents were tested for sample pre-concentration, including
      numerous polymeric based phases. Bond Elut PPL and Oasis HLB were the only phases
      capable of retaining the majority of the target analyte classes in a single
      method. An off-line pre-concentration method using a Gilson Aspec system was
      optimised using the Bond Elut PPL cartridges, with a concentration factor of 25
      producing limits of quantitation in the order of 6-100 ng/L. Excellent linearity
      (r2 > 0.9), precision (<20%) and recovery (>60%) was obtained for nearly all of
      the analytes, covering a wide variety of chemical and physical properties. This
      is the first study to fully validate Bond Elut PPL cartridges for use in multi
      residue pesticide analysis.

PMID- 19575188
TI  - Application of a new anti-zearalenone monoclonal antibody in different
      immunoassay formats.
AB  - Monoclonal antibodies against zearalenone (ZEA) were raised in mice according to
      the hybridoma technology and applied in different immunochemical techniques. More
      specifically, three formats based on the competitive direct enzyme immunoassay
      principle were developed: an enzyme-linked immunosorbent assay (ELISA), a flow
      through gel-based immunoassay column and a flow-through membrane-based
      immunoassay. In ELISA, the 50% inhibitory concentration (IC50) was 0.8 ng/mL, and
      the limit of detection for ZEA standard solutions was 0.1 ng/mL. The antibodies
      showed a high ZEA (100%) and alpha-zearalenol (alpha-ZOL) (69%) recognition,
      while cross-reactivities with alpha-zearalanol, zearalanone, beta-zearalenol and
      beta- zearalanol were 42%, 22%, <1% and <1%, respectively. For standard
      solutions, a cut-off level at 10 ng/mL could be established for the gel- and
      membrane-based enzyme immunoassays. Assay time of both non-instrumental tests was
      25 min for 10 samples. By including a simple sample extraction procedure, the
      methods were applied to wheat with IC50s in ELISA of 80 and 120 microg/kg
      (dilution up to 5% and 15% (v/v) of wheat matrix, respectively). The cut-off
      level of the gel- and membrane-based immunoassays was established at 100
      microg/kg. Potentials and limitations of the developed methods were compared. The
      possible application for multi-mycotoxin analysis of the ELISA method based on a
      single monoclonal antibody was investigated. Therefore, principal component
      analysis and partial least squares regression data modelling were used to
      separate the immunoassay responses of two cross-reactants (ZEA and alpha-ZOL).

PMID- 19575189
TI  - Development of an enzyme-linked immunosorbent assay for metolcarb residue
      analysis and investigation of matrix effects from different agricultural
      products.
AB  - The development of a direct competitive enzyme-linked immunosorbent assay based
      on polyclonal antibodies for N-methylcarbamate insecticide metolcarb is
      described. Two new haptens for the metolcarb were designed and synthesized. Both
      haptens were conjugated with keyhole limpet hemocyanin to form the immunogens.
      Four rabbits were immunized with the immunogens for production of polyclonal
      antibodies against metolcarb. Antisera titers were tested on the homologous
      coating antigens using a noncompetitive indirect enzyme-linked immunosorbent
      assay. The high titer antisera were used to develop the direct competitive enzyme
      linked immunosorbent assay for the detection of metolcarb. The antibody-antigen
      combination with the highest selectivity for metolcarb was further optimized and
      its tolerance to changes in chemical conditions (ionic strength, pH value, and
      organic solvent) was studied. Under optimum conditions, the sensitivity and the
      limit of detection were determined to be 22 microg L(-1) and 1.2 microg L(-1)
      respectively. Determination of metolcarb in fruit juices and vegetables was
      accomplished by simple, rapid, and efficient extraction methods. Recoveries of
      metolcarb from spiked samples ranged from 80.5% to 109.5%. Validation of the
      developed immunosorbent assay was conducted by comparison of results from high
      performance liquid chromatography. The correlation between the data obtained
      using developed immunosorbent assay and high-performance liquid chromatography
      was high (R2 = 0.9884). Therefore, the developed immunosorbent assay in this
      study was suitable for the rapid quantitative determination of metolcarb in
      agricultural products.

PMID- 19575190
TI  - Development of a multichannel flow-through chemiluminescence microarray chip for
      parallel calibration and detection of pathogenic bacteria.
AB  - Pathogen detection is important for health and safety reasons. Several outbreaks
      all over the world have shown the need for rapid, qualitative, quantitative, and,
      particularly, multianalyte detection systems. Hence, a multichannel flow-through
      chemiluminescence microarray chip for parallel detection of pathogenic bacteria
      was developed. The disposable chip made of acrylonitrile-butadiene-styrene (ABS)
      copolymer was devised as a support for a multiplexed sandwich immunoassay.
      Calibration and measurement was possible in one experiment, because the developed
      chip contains six parallel flow-through microchannels. Polyclonal antibodies
      against the pathogenic bacteria Escherichia coli O157:H7, Salmonella typhimurium,
      and Legionella pneumophila were immobilized on the chip by microcontact printing
      in order to use them as specific receptors. Detection of the captured bacteria
      was carried out by use of specific detection antibodies labelled with biotin and
      horseradish peroxidase (HRP)-streptavidine conjugates. The enzyme HRP generates
      chemiluminescence after adding luminol and hydrogen peroxide. This signal was
      observed by use of a sensitive CCD camera. The limits of detection are 1.8 x
      10(4) cells mL(-1) for E. coli O157:H7, 7.9 x 10(4) cells mL(-1) for L.
      pneumophila, and 2.0 x 10(7) cells mL(-1) for S. typhimurium. The overall assay
      time for measurement and calibration is 18 min, enabling very fast analysis.

PMID- 19575191
TI  - Chromatographic evaluation of polymers imprinted with analogs of chloramphenicol
      and application to selective solid-phase extraction.
AB  - To obtain a highly selective material for the antibiotic chloramphenicol, which
      has several harmful side effects in humans, different molecularly imprinted
      polymers (MIPs) were prepared. In order to avoid a major traditional drawback
      associated with MIPs of residual template bleeding, molecules that are
      structurally related to chloramphenicol were used as templates for polymer
      synthesis. Chromatographic evaluation indicated that the employed template
      imparted a significant influence on the recognition properties of the
      corresponding polymer. A strong retention of chloramphenicol under nonpolar
      elution conditions (k = 68.03, IF = 17.72) and under aqueous elution conditions
      (k = 92.44, IF = 1.35) was achieved. After chromatographic evaluation, the MIP
      was utilized as the recognition sorbent in a solid-phase extraction to determine
      chloramphenicol using either an organic or aqueous washing solvent. Recoveries of
      nearly 100% from the chloramphenicol standard solution and nearly 90% from honey
      samples spiked with chloramphenicol were attained. Furthermore, the applicability
      of the MIP for sample cleanup was demonstrated.

PMID- 19575192
TI  - Microextraction, capillary electrophoresis, and mass spectrometry for forensic
      analysis of azo and methine basic dyes from acrylic fibers.
AB  - Designed experiments based on a simplex mixture design were employed to explore
      the effects of three solvent components (water, formic acid, and aqueous acetic
      acid), extraction time, and extraction temperature for the automated
      microextraction of basic (cationic) dyes from acrylic fibers. Extractions were
      conducted by an automated liquid handling system, and dye extraction was
      evaluated using a UV/visible microplate reader. Highest extraction efficiency for
      two subclasses of basic dyes (methine and azo) from acrylic fibers was achieved
      with an extraction solvent containing 88% formic acid/12% water. Cationic dyes
      were analyzed by capillary electrophoresis using a 45 mM ammonium acetate buffer
      in acetonitrile-water at pH 4.7. The utility of microextraction combined with
      capillary electrophoresis-mass spectrometry for analysis of extracts from trace
      fibers was demonstrated by the detection and characterization of three basic dyes
      extracted from a 2-mm length of single acrylic fiber.

PMID- 19575193
TI  - Urea nitrate, an exceptionally easy-to-make improvised explosive: studies towards
      trace characterization.
AB  - Urea nitrate is a powerful improvised explosive, frequently used by terrorists in
      the Israeli arena. It was also used in the first World Trade Center bombing in
      New York in February 1993. It is difficult to identify urea nitrate in post
      explosion debris, since only a very small fraction survives the blast. Also, in
      the presence of water, it readily decomposes to its original components, urea and
      nitric acid. It is suspected that post-blast debris of urea nitrate can be
      confused with ammonium nitrate, the main solid product of urea nitrate thermal
      decomposition. In a comprehensive study towards identification of urea nitrate in
      post-blast traces, a spectrophotometric technique for quantitative determination
      of urea nitrate was developed, and conditions were found for extraction and
      separation of un-exploded traces of urea nitrate with minimal decomposition.
      Nevertheless, out of 28 samples collected from a series of three controlled
      firings of urea nitrate charges, only one gave the typical adduct ion by liquid
      chromatography/mass spectrometry analysis. We found that urea nitrate can be
      extracted from solid mixtures to organic solvents by using Crown ethers as "host
      compounds." The adducts thus formed are solid, crystalline compounds that can be
      characterized by microanalysis and spectroscopic techniques.

PMID- 19575194
TI  - Confined detection volume of fluorescence correlation spectroscopy by bare fiber
      probes.
AB  - A fiber-tip-based near-field fluorescence correlation spectroscopy (FCS) has been
      developed for confining the detection volume to sub-diffraction-limited
      dimensions. This near-field FCS is based on near-field illumination by coupling a
      scanning near-field optical microscope (SNOM) to a conventional confocal FCS.
      Single-molecule FCS analysis at 100 nM Rhodamine 6G has been achieved by using
      bare chemically etched, tapered fiber tips. The detection volume under control of
      the SNOM system has been reduced over one order of magnitude compared to that of
      the conventional confocal FCS. Related factors influencing the near-field FCS
      performance are investigated and discussed in detail. In this proof-of-principle
      study, the preliminary experimental results suggest that the fiber-tip-based near
      field FCS might be a good alternative to realize localized analysis at the single
      molecule level.

PMID- 19575195
TI  - Characterization of endo-beta-1,4-glucanase from a novel strain of Penicillium
      pinophilum KMJ601.
AB  - A novel endo-beta-1,4-glucanase (EG)-producing strain was isolated and identified
      as Penicillium pinophilum KMJ601 based on its morphology and internal transcribed
      spacer (ITS) rDNA gene sequence. When rice straw and corn steep powder were used
      as carbon and nitrogen sources, respectively, the maximal EG activity of 5.0 U mg
      protein(-1), one of the highest levels among EG-producing microorganisms, was
      observed. The optimum temperature and pH for EG production were 28 degrees C and
      5.0, respectively. The increased production of EG by P. pinophilum in culture at
      28 degrees C was confirmed by two-dimensional electrophoresis followed by MS/MS
      sequencing of the partial peptide. A partial EG gene (eng5) was amplified by
      degenerate polymerase chain reaction (PCR) based on the peptide sequence. A full
      length eng5 was cloned by genome-walking PCR, and P. pinophilum EG was identified
      as a member of glycoside hydrolase family 5. The present results should
      contribute to improved industrial production of EG by P. pinophilum KMJ601.

PMID- 19575196
TI  - Positive association between increased popliteal artery vessel wall thickness and
      generalized osteoarthritis: is OA also part of the metabolic syndrome?
AB  - PURPOSE: The purpose of the study was to determine if a positive association
      exists between arterial vessel wall thickness and generalized osteoarthritis
      (OA). Our hypothesis is that generalized OA is another facet of the metabolic
      syndrome. MATERIALS AND METHODS: The medical ethical review board of our
      institution approved the study. Written informed consent was obtained from each
      patient prior to the study. Magnetic resonance (MR) images of the knee were
      obtained in 42 patients who had been diagnosed with generalized OA at multiple
      joint sites. Another 27 MR images of the knee were obtained from a matched normal
      (non-OA) reference population. Vessel wall thickness of the popliteal artery was
      quantitatively measured by dedicated software. Linear regression models were used
      to investigate the association between vessel wall thickness and generalized OA.
      Adjustments were made for age, sex, and body mass index (BMI). Confidence
      intervals (CI) were computed at the 95% level and a significance level of alpha =
      0.05 was used. RESULTS: Patients in the generalized OA population had a
      significant higher average vessel wall thickness than persons from the normal
      reference population (p < or = alpha), even when correction was made for sex,
      age, and BMI. The average vessel wall thickness of the popliteal artery was 1.09
      mm in patients with generalized OA, and 0.96 mm in the matched normal reference
      population. CONCLUSION: The association found between increased popliteal artery
      vessel wall thickness and generalized osteoarthritis suggests that generalized OA
      might be another facet of the metabolic syndrome.

PMID- 19575197
TI  - The effect of right ventricular pacing on myocardial oxidative metabolism and
      efficiency: relation with left ventricular dyssynchrony.
AB  - PURPOSE: Right ventricular (RV) apical pacing induces dyssynchrony by a left
      bundle branch block type electrical activation sequence in the heart and may
      impair left ventricular (LV) function. Whether these functional changes are
      accompanied by changes in myocardial perfusion, oxidative metabolism and
      efficiency, and the relation with the induction of LV dyssynchrony are unknown.
      Our study was designed to investigate the acute effects of RV pacing on these
      parameters. METHODS: Ten patients with normal LV ejection fraction and VVI/DDD
      pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing
      OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [15O]water
      and [11C]acetate positron emission tomography was used to measure perfusion and
      oxidative metabolism (kmono) of the LV. An echocardiographic examination was used
      to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of
      forward work was calculated as systolic blood pressure * cardiac output/LV
      mass/kmono. RESULTS: RV pacing decreased SV in all subjects (mean decrease 13%,
      from 76 +/- 7 to 66 +/- 7 ml, p = 0.004), but global perfusion and kmono were
      unchanged. The efficiency tended to be lower with pacing-ON (70 +/- 20 vs 81 +/-
      21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6)
      efficiency decreased by 23% (from 78 +/- 25 to 60 +/- 14 mmHg l/g, p = 0.02), but
      in patients without dyssynchrony no change in efficiency was detected.
      Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was
      detected during pacing in patients with dyssynchrony but not in those without
      dyssynchrony. CONCLUSION: RV pacing resulted in a significant decrease in SV.
      However, deleterious effects on LV oxidative metabolism and efficiency were
      observed only in patients with dyssynchrony during RV pacing.

PMID- 19575198
TI  - Toxic non-resorptive internal hydrocephalus as a result of haemorrhagic
      ventriculitis during induction chemotherapy of Bcr-Abl positive acute
      lymphoblastic leukaemia.

PMID- 19575199
TI  - A case report of non-traumatic renal artery pseudoaneurysm due to chemotherapy
      for diffuse large B-cell lymphoma.

PMID- 19575200
TI  - A phase II study of gemcitabine and oxaliplatin (Oxigem) in unresectable gall
      bladder cancer.
AB  - PURPOSE: There is a need for effective chemotherapy protocols for gall bladder
      cancer (GBC). Gemcitabine has antitumor activity in pancreatic cancer.
      Oxaliplatin is effective in GI cancers. Based on evidence of synergy between
      these two, we designed this study to evaluate efficacy of this combination in
      unresectable GBC. DESIGN: Unresectable GBC was enrolled for single center phase
      II study. Drugs gemcitabine 900 mg/m2 and oxaliplatin 80 mg/m2 IV infusion
      (Oxigem) on days 1 and 8 every 3 weeks for a maximum of six cycles or
      unacceptable toxicity which ever was earlier. MATERIALS AND METHODS: Fifty
      patients were enrolled and analysis was restricted to 48 who were treated. Median
      age was 50 years and 31 patients were females. RESULTS: CR 3 (6.2%), PR 7 (15%),
      SD 17 (35.4%), and PD 18. One had complete pathological response. Median OS and
      PFS were 7.5 and 3 months, respectively. OS in responders was 10.5 versus 4
      months in non-responders (p<0.0000). Eleven patients (23%) survived for a year or
      more. There was no toxic death and grade III/IV toxicity seen in 10 (22%)
      patients: diarrhea 3, vomiting 2, neutropenia and thrombocytopenia 5 patients.
      CONCLUSION: This combination of Oxigem effective in unresectable GBC. It may even
      induce complete pathological response. One-year survival was 20%. There is a need
      for controlled trial to assess efficacy of this combination.

PMID- 19575201
TI  - Polyarthritis with chondronecrosis associated with osteonecrosis, panniculitis
      and pancreatitis.
AB  - Arthritis associated with panniculitis complicating pancreatitis is well
      described in the literature, usually associated with osteonecrosis.
      Chondronecrosis has not been reported before in association with pancreatitis. We
      report a patient with chronic pancreatitis who presented with polyarthritis,
      panniculitis, osteonecrosis, but in addition had clear evidence of
      chondronecrosis. We suggest that direct extension of noxious materials from
      nearby subchondral osteonecrotic bone lesion could be the cause of the
      osteonecrosis and one of the pathological mechanisms leading to arthritis in
      patients with pancreatitis.

PMID- 19575202
TI  - Familial Behcet's disease.
AB  - Behcet's disease (BD) is a multisystemic vasculitis syndrome characterized by a
      course of remissions and exacerbations of unpredictable frequency and duration.
      The disease has a worldwide distribution, but the majority of cases cluster along
      the ancient Silk Road, which extends from eastern Asia to the Mediterranean
      basin. The etiopathogenesis of BD is still unknown, but familial aggregation and
      peculiar geographical distribution have been regarded as evidence supporting
      genetic influence on the pathogenesis of BD. In this article, we describe a
      patient with BD, who had four members of his family associated with BD.

PMID- 19575203
TI  - Level of circulating CD4+ 28null cells in chronic inflammatory diseases: an
      important marker in predicting acute coronary events?

PMID- 19575204
TI  - [Functional glaucoma diagnosis].

PMID- 19575205
TI  - [Tears from an art historical point of view].
AB  - Drawing on works of literature, philosophy and art the author tries to unearthen
      the multiple meanings of tears and crying in the history of the fine arts. The
      essay spans from pictures of the earliest known representations of tears in the
      Middle Ages to the tears found in photographies of the Modern Arts of nowadays.

PMID- 19575206
TI  - [Neovascular age-related macular degeneration under anti-angiogenic therapy :
      Subretinal fluid is a relevant prognostic parameter].
AB  - BACKGROUND: Due to its progressive nature neovascular age-related macular
      degeneration (nAMD) is the most common cause of irreversible vision loss and
      blindness in people aged 60 or older. Optical coherence tomography (OCT) plays an
      important role in monitoring this exudative disease. However, prognostic factors
      for visual rehabilitation under anti-angiogenic therapy are still rare. It was
      the aim of this study to identify prognostic parameters based on OCT. METHODS: In
      this study 17 patients with nAMD were included and treated with 3 intravitreal
      ranibizumab injections. Stratus-OCT and Cirrus-OCT imaging were performed to
      identify prognostic factors. Different OCT parameters, such as the volume of
      subretinal fluid and the degree of serous retinal detachment in the fovea, were
      analyzed and correlated with visual acuity (VA). RESULTS: Baseline VA was an
      important prognostic factor correlating with final VA at the end of the study.
      Retinal thickness measured by OCT showed a correlation to VA at the time of
      examination but not with the final results.. The volume of subretinal fluid
      (SRFV) however, correlated significantly with VA at weeks 4 and 12. The degree of
      serous retinal detachment of the fovea did not correlate with retinal function.
      CONCLUSION: Data show that some retinal thickness values correlated to VA in the
      spectral domain OCT but not in Stratus OCT. In this study VA at baseline and the
      SRFV were the most important prognostic factors for VA at 3 months.. This
      demonstrates the important role of SRFV measurements as a relevant prognostic
      factor in nAMD and encourages more research into the analysis of OCT parameters
      in order to have a better understanding of the prognosis of individual patients
      receiving anti-angiogenic therapy for nAMD.

PMID- 19575207
TI  - Carotenoids in nestling Montagu's harriers: variations according to age, sex,
      body condition and evidence for diet-related limitations.
AB  - Carotenoids are colored pigments forming the basis of many avian social traits.
      Before their utilization carotenoids must be acquired through diet and mobilized
      for specific uses. The relationships between carotenoid-based coloration,
      circulating carotenoids and body condition have been well studied in adult birds,
      but little is known in nestlings. Here, we investigated variations in carotenoid
      based coloration in a raptor nestling, the Montagu's harrier (Circus pygargus),
      both in captivity and in natural conditions, and within a vole (poor-carotenoid
      source and cyclic prey) specialist population. We studied these variations
      according to nestling age and sex, and possible limitations in carotenoid
      availability by comparing years of contrasted prey abundance and using carotenoid
      supplementation experiments. Captive nestlings, fed only with mice, were strongly
      carotenoid limited. Wild nestlings were also carotenoid limited, especially in a
      year of high vole abundance. Nestlings were in better condition but less colored
      during a peak vole abundance year than during a low vole abundance year, when
      harriers targeted more alternative preys (birds, insects). Thus, variation in
      vole abundance resulted in a de-coupling of body condition and carotenoid-based
      coloration in this population. This suggested that the positive relation between
      the body condition and carotenoid-based traits, typically found in adult birds,
      could be restricted to adults or nestlings of species that feed on carotenoid
      rich food. Our results should stimulate more work on the functions and mechanisms
      of carotenoid-based traits in nestlings, which deserve more attention and most
      likely differ from those of adult birds.

PMID- 19575208
TI  - Effectiveness of skull models and surgical simulation: comparison of outcome
      between different surgical techniques in patients with isolated brachycephaly.
AB  - PURPOSE: The aim of this study was to emphasize the importance of preoperative
      surgical planning using 3D skull models in craniosynostosis surgery. METHODS: By
      using 3D polymethyl methacrylate skull models manufactured using 3D tomography
      images, the authors previously showed that after fronto-parietal osteotomy,
      instead of fixing the fronto-parietal bone flap without rotation, angled
      advancement with horizontal osteotomy provides maximum increase in intracranial
      volume, in a bilateral coronal craniosynostosis model. After changing the
      operation technique using data gathered from previous studies, we reviewed two
      bilateral craniosynostosis patients operated with the new technique and compared
      it with two patients that were operated with the old technique. RESULTS:
      Comparing cranial indexes (CI), significant improvement was detected in both
      groups. The decrease in CI in the second group was slightly better than the first
      group. In the comparison of intracranial volume (ICV), there was an increase in
      ICV values in both groups. The percentage of increase between two groups was
      similar. The morphological outcome was satisfactory in all patients. There were
      no major or minor complications and morbidity. CONCLUSIONS: Current multislice
      tomography technology and stereolithographic procedures provide an excellent
      surgical simulation model to find new techniques and predict the outcome. These
      models should be used in all complex and syndromic craniosynostosis for both
      better results and reducing the operative time and associated blood loss.

PMID- 19575210
TI  - A simple quality of life questionnaire for patients with faecal incontinence.
AB  - INTRODUCTION: A simple quality of life questionnaire was designed to triage
      patients with faecal incontinence to the most appropriate level of support,
      investigation and treatment. METHOD: A questionnaire was developed to include a
      'symptom' score, similar in content to St Mark's questionnaire and a 'bothersome'
      score. A pilot study (34 patients) assessed the clarity of questions. Once
      content validity was established, it was sent to 360 patients who attended a
      pelvic floor clinic. Its external validity was assessed against the established
      standards of the short form 36 (SF-36) and the Manchester Health Questionnaires.
      Ease of use for these was assessed using a separate form. RESULTS: Of the 360
      patients, 86 replied. The questionnaire was shown to be reliable both by
      measurement of its internal consistency and by test-retest analysis. There was a
      significant correlation between the scores of the new questionnaire and the
      Manchester Health Questionnaire as well as the SF-36. Divergence validity,
      assessed by correlating the number of pads used and the overall symptom score,
      was established. The new questionnaire was easiest to complete, taking on average
      4 min. CONCLUSION: We have demonstrated that the new questionnaire is reliable
      and valid. It is easy and quick to complete and assesses both severity and impact
      of symptoms.

PMID- 19575211
TI  - [Recurrent spontaneous abortion--is heparin expendable to recurrence
      prophylaxis?].

PMID- 19575213
TI  - Rye B chromosomes are weakly transcribed and might alter the transcriptional
      activity of A chromosome sequences.
AB  - B chromosomes (Bs) are dispensable components of the genomes of numerous species.
      To test whether the transcriptome of a host is influenced by Bs, we looked for
      differences in expression in response to additional Bs. Comparative complementary
      DNA amplified fragment length polymorphism experiments resulted in the
      identification of 16 putative B-chromosome-associated transcripts. This comprises
      0.7% of the total transcript number and indicates a low activity of Bs. We also
      provide evidence that B chromosome influences in trans the transcription of A
      chromosome sequences. The B-specific transcribed sequences B1334, B8149, and
      B2465 belong to high-copy families with similarity to mobile elements. For all
      analyzed B-chromosome-derived transcripts, similar A chromosome-encoded sequences
      were found which supports an A-derived origin of rye B chromosomes.

PMID- 19575214
TI  - Positional statement of the European Society of Endocrine Surgeons (ESES) on
      modern techniques in pHPT surgery.

PMID- 19575215
TI  - How to perform a thyroidectomy in an outpatient setting.
AB  - PURPOSE: In France, the current practice for postoperative care of thyroidectomy
      is still inpatient care. No series of outpatient thyroidectomy has been reported.
      The aim of this work was to assess the acceptability, feasibility, and safety of
      outpatient unilateral thyroid lobectomy in a university hospital. MATERIALS AND
      METHODS: The procedure was proposed to patients presenting with nodule(s) in one
      lobe of the thyroid and fulfilling predetermined inclusion criteria. The surgical
      protocol included no drainage and, progressively, no dressing. Standard
      anesthetic, analgesic, and antiemetic protocols were used. Unplanned admission,
      complication, and re-operation rates were evaluated. RESULTS: Among 153
      unilateral thyroid lobectomies performed, 95 (62%) were planned for outpatient
      surgery. The proportion of outpatient unilateral thyroid lobectomies increased
      during an 8-year period from 36% to 90%. One patient was re-operated because
      local hemorrhage was diagnosed in the recovery room. He was discharge the next
      day. Eighteen patients (13.7%) were admitted because of nausea (n = 6),
      dizziness, and physical discomfort mostly due to anxiety (n = 5). Seventy-seven
      patients were discharged as planned 6 to 8 h after the operation. No patient was
      readmitted. CONCLUSIONS: Outpatient unilateral thyroid lobectomy is feasible and
      safe in the setting of appropriate facilities and management protocol. Strict
      control of postoperative nausea is essential, and a preoperative education for
      ambulatory surgery is useful to minimize patient anxiety and increase
      acceptability.

PMID- 19575216
TI  - Clinical and diagnostic relevance of Meckel's diverticulum in children.
AB  - Meckel's diverticulum (MD) has varied clinical manifestations and is a diagnostic
      challenge for pediatricians. This study investigates the clinical and diagnostic
      characteristics of MD in children with different presentations. We
      retrospectively reviewed the medical records of pediatric patients diagnosed with
      MD from 1988 to 2008. The data including the age, sex, clinical features,
      laboratory data, sensitivity of diagnostic methods, and pathological finding were
      recorded. These patients were classified into three groups: diverticulitis,
      intestinal obstruction, and intestinal bleeding. A total of 47 children (35 boys
      and 12 girls) with a median age of 5.6 years were enrolled and categorized as
      follows: diverticulitis (n = 12), obstruction (n = 12), bleeding (n = 21), and
      two diagnosed incidentally. Patients with intestinal obstruction were
      significantly younger than those with bleeding (3.7, 95% CI, 1.6-5.7 vs. 6.6, 95%
      CI, 4.5-8.7, P = 0.04). In the obstruction group, intussusception was found in
      eight of 12 patients, of whom 62.5% were aged older than 3 years. Heterotopic
      tissues were found in 46.3% of surgical specimens and more frequently existed in
      patients with bleeding than those with diverticulitis (P = 0.02) and obstruction
      (P = 0.047). Tc-99m scans yielded a diagnostic sensitivity of about 65% in
      bleeding patients. Repeated Tc-99m scans and red blood cell (RBC) scans can be
      good supplementary tools in Tc-99m scan-negative bleeding patients. In
      conclusion, manifestations of childhood MD are variable and may depend on the
      presence of heterotopic tissues and the patients' age. Tc-99m scans supplemented
      with RBC scans are appropriate to diagnose childhood MD with bleeding.

PMID- 19575217
TI  - Mosquito larvicidal activities of extractives from black heartwood-type
      Cryptomeria japonica.
AB  - The purpose of this study is to determine the larvicidal activities of ethanolic
      extracts from leaves, wood, and bark of black heartwood-type Cryptomeria japonica
      against fourth-instar larvae of mosquitoes Aedes aegypti and Aedes albopictus.
      Among three ethanolic extracts from C. japonica, wood extract exhibited the best
      larvicidal activity against A. aegypti and A. albopictus with LC(50) values of
      63.2 and 93.8 microg/ml, respectively. Four major compounds, including
      ferruginol, epi-cubebol, cubebol, and isopimarol, were isolated from wood
      extract, and it was demonstrated that cubebol exhibited the best activity against
      A. aegypti and A. albopictus with LC(50) values of 60.1 and 50.0 microg/ml,
      respectively. Our findings showed that the wood extract and cubebol from C.
      japonica have good potential as a source for natural larvicides.

PMID- 19575218
TI  - Intrapopulational distribution of Meiogymnophallus minutus (Digenea,
      Gymnophallidae) infections in its first and second intermediate host.
AB  - Host size and age are generally assumed to play a pivotal role in digenean
      trematode infection patterns, accounting for much of the variation found within
      intermediate host populations. However, knowledge is based on a limited number of
      studied host-parasite systems. We investigated the shell length class
      distribution of Meiogymnophallus minutus infections within populations of the
      first intermediate host Scrobicularia plana and second intermediate host
      Cerastoderma edule. Infections occurred very early in the life of the two
      intermediate hosts. Both prevalence and intensity of infections increased with
      host shell length and displayed extremely high values amongst large individuals.
      Whilst metacercarial infection patterns in juvenile C. edule could be best
      explained by differences in host shell length, in adult cockles, the effect of
      host age on infection levels prevailed. The microsporidian hyperparasite
      Unikaryon legeri, occurring in the metacercarial stage of M. minutus, was
      particularly abundant in aged cockles, strongly influencing infection patterns of
      the gymnophallid. Our results are consistent with the intrapopulational
      distribution reported from other digenean trematode parasites. The relative
      influence of both host size and age and the underlying mechanisms as well as the
      impact of hyperparasitism on M. minutus infection patterns are discussed.

PMID- 19575219
TI  - Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs)
      against mature and immature infections with Toxocara canis and Toxascaris leonina
      in dogs.
AB  - The efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs)
      against mature adult, immature adult and larval stages of Toxocara canis and
      Toxascaris leonina was evaluated in ten randomised, blinded and placebo
      controlled dose confirmation studies in naturally or experimentally infected
      dogs. The tablets were used at the proposed minimum dose of 1 mg emodepside and 5
      mg praziquantel per kg body weight. Efficacy was calculated based on worm counts
      after necropsy. Five studies demonstrated >99% efficacy against mature adult,
      >92% efficacy against immature adult, >98% efficacy against L4 and >94% efficacy
      against L3 larval stages of T. canis. Another five studies demonstrated >99%
      efficacy against mature and immature adult and >95% efficacy against L4 larval
      stages of T. leonina. No side effects of the treatment were observed. Emodepside
      plus praziquantel tablets thus provide a comprehensive new treatment option for
      ascarid infections in the dog.

PMID- 19575220
TI  - Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs)
      against mature and immature adult Ancylostoma caninum and Uncinaria stenocephala
      infections in dogs.
AB  - This paper reports the efficacy of a novel flavoured tablet formulation of
      emodepside plus praziquantel (Profender tablets for dogs) against mature and
      immature adult hookworms (Ancylostoma caninum and Uncinaria stenocephala) in
      dogs. The tablets were used at the minimum recommended dose of 1 mg emodepside
      and 5 mg praziquantel per kg body weight. Four randomised, blinded and controlled
      laboratory studies demonstrated >95% efficacy against mature and immature adult
      stages of U. stenocephala and four randomised, blinded and controlled laboratory
      studies demonstrated >98% efficacy against mature and immature adult stages of A.
      caninum. No side effects of the treatment were observed. It is concluded that the
      emodepside plus praziquantel tablet is an effective and safe treatment against
      mature and immature hookworms.

PMID- 19575221
TI  - Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs)
      against mature and immature adult Trichuris vulpis infections in dogs.
AB  - This paper reports on the efficacy of a novel flavoured tablet formulation of
      emodepside plus praziquantel (Profender tablets for dogs) against mature and
      immature adult whipworms (Trichuris vulpis) at the proposed minimum dose of 1 mg
      emodepside and 5 mg praziquantel per kg body weight in dogs. Three randomised,
      blinded and controlled laboratory studies with naturally or experimentally
      infected dogs were performed. The first study was conducted as a dose
      determination study in experimentally infected dogs using three different dose
      levels, i.e., 0.5x, 1x and 2x the minimum therapeutic dose. Two further studies
      confirmed the efficacy of emodepside plus praziquantel tablets against mature and
      immature adult T. vulpis at the recommended minimum dose. In all three studies,
      the efficacy against mature and immature adult T. vulpis was >99%. No side
      effects of the treatment were observed. It is concluded that the emodepside plus
      praziquantel tablet is an effective and safe treatment against mature and
      immature adult stages of T. vulpis in dogs.

PMID- 19575222
TI  - Field evaluation of the efficacy and safety of emodepside plus praziquantel
      tablets (Profender tablets for dogs) against naturally acquired nematode and
      cestode infections in dogs.
AB  - A controlled, blinded and randomised multicentre field study evaluated the
      efficacy and safety of a new anthelmintic tablet formulation containing
      emodepside plus praziquantel (Profender tablets for dogs) in the treatment of
      gastrointestinal nematode and cestode infections in dogs in France, Germany,
      Portugal and Slovakia. Dogs positive for nematodes and/or cestodes (demonstrated
      by faecal egg counts and/or the presence of proglottids) were treated with
      emodepside plus praziquantel tablets (n = 239) or the reference product
      containing milbemycin oxime and praziquantel (Milbemax [n = 115]) at the
      recommended dose rate. Two faecal samples collected between 7 and 13 days after
      treatment were evaluated for proglottids, nematode and cestode eggs. No suspected
      adverse drug reactions were observed in the study. The following parasite species
      were identified: Trichuris vulpis, Toxocara canis, Toxascaris leonina, Uncinaria
      stenocephala, Ancylostoma caninum, Dipylidium caninum, Taeniidae and
      Mesocestoides spp. Geometric mean nematode egg counts in dogs treated with
      emodepside plus praziquantel tablets were reduced by 99.9 % compared with a
      reduction of 99.6 % for the reference product. Statistical analysis demonstrated
      noninferiority of investigational versus reference product (p = 0.0342). None of
      the dogs treated with emodepside plus praziquantel or reference product remained
      positive for cestodes after treatment. The study demonstrated that emodepside
      plus praziquantel tablets are safe and highly efficacious against a broad
      spectrum of nematodes and cestodes under field conditions.

PMID- 19575223
TI  - Efficacy of emodepside plus praziquantel tablets (Profender tablets for dogs)
      against mature and immature cestode infections in dogs.
AB  - The efficacy of a novel flavoured tablet formulation of emodepside plus
      praziquantel (Profender tablets for dogs) against intestinal cestodes was
      investigated in four randomised, blinded placebo-controlled dose confirmation
      studies in dogs experimentally infected with Echinococcus granulosus or E.
      multilocularis and in dogs naturally infected with Dipylidium caninum or Taenia
      spp. The tablets were used at the minimum recommended dose of 1 mg emodepside and
      5 mg praziquantel per kg body weight. The studies demonstrated 100% efficacy
      against mature and immature E. granulosus and E. multilocularis and mature Taenia
      spp. and D. caninum. Additionally, one of the studies demonstrated non
      interference of emodepside with the efficacy of praziquantel against D. caninum.
      No side effects of the treatment were observed. It is concluded that emodepside
      plus praziquantel tablets are safe and effective against mature and immature
      stages of E. granulosus and E. multilocularis and mature stages of Taenia spp.
      and D. caninum.

PMID- 19575224
TI  - Natural infections of Angiostrongylus vasorum and Crenosoma vulpis in dogs in
      Germany (2007-2009).
AB  - In order to assess the occurrence and regional geographical distribution of
      Angiostrongylus vasorum and Crenosoma vulpis in Germany, faecal samples of 810
      dogs with clinical symptoms of respiratory and circulatory disease, bleeding
      disorder and/or neurological signs were collected from September 2007 to March
      2009. The zinc chloride/sodium chloride flotation and Baermann funnel technique
      were used to examine the samples for presence of lungworm larvae. Infections with
      lungworms were diagnosed in 105 (13.0%) of the examined dogs. A. vasorum and C.
      vulpis were found in 60 (7.4%) and 49 (6.0%) faecal samples, respectively. 33 A.
      vasorum- and 12 C. vulpis-positive dogs were located in Baden-Wurttemberg, 13 and
      12 in North Rhine-Westphalia, 3 and 4 in Bavaria, 1 and 7 in Rhineland
      Palatinate, 7 and 4 in Saarland, 1 and 2 in Saxony, respectively. In Brandenburg
      only 2 dogs with A. vasorum and in Hesse a total of 5 dogs with C. vulpis were
      detected. In Mecklenburg-Western Pomerania, Lower Saxony and Thuringia only 1 dog
      with C. vulpis was detected at a time. 4 dogs were coinfected with A. vasorum and
      C. vulpis. These surprisingly high prevalence rates indicate that both parasites
      are endemic in Germany.

PMID- 19575225
TI  - Efficacy of a single topical application of Advantage Multi (= Advocate) Topical
      Solution (10% imidocloprid + 2.5% moxidectin) in the treatment of dogs
      experimentally infected with Crenosoma vulpis.
AB  - Crenosoma vulpis is a metastrongylid lungworm of canids causing chronic
      respiratory disease in dogs in parts of North America and Europe. The objective
      of this study was to determine the efficacy of imidacloprid 10% + moxidectin 2.5%
      (Advantage Multi/Advocate Topical Solution) against C. vulpis infection in
      experimentally infected dogs. Eighteen beagles (9 M, 9 F) were each given 100
      infective third-stage larvae of C. vulpis. The 16 dogs (8 M, 8 F) with the
      highest faecal larval counts were stratified by gender and larval counts and
      randomly assigned to a treatment group. Group 1 received placebo only; group 2
      was given a single topical treatment of Advantage Multi/Advocate (10 mg/kg
      imidacloprid/2.5 mg/kg moxidectin) at 4 weeks PI. Dogs were euthanised at 8 weeks
      PI and the lungs were removed and examined for the presence of adult worms by
      lung flush. The mean (geometric) number for adult C. vulpis recovered in
      untreated dogs was 70.0 (range 58 to 87) compared with 0.0 in animals treated
      with Advantage Multi/Advocate. The resulting efficacy against C. vulpis was 100%.
      The number of C. vulpis was significantly lower for treated dogs than the burden
      shown in the untreated group (p = 0.003).

PMID- 19575226
TI  - Efficacy and safety of imidacloprid 10%/moxidectin 1% spot-on formulation in the
      treatment of feline aelurostrongylosis.
AB  - The objective of the present study was to evaluate the efficacy and safety of the
      antiparasitic spot-on formulation containing imidacloprid 10%/moxidectin 1%
      (Advocate, Bayer) in the treatment of natural feline infection with the lungworm
      Aelurostrongylus abstrusus (Nematoda, Strongylida). The efficacy of Advocate
      administered once was tested in comparison to a control oral formulation
      containing fenbendazole 18.75% (Panacur Intervet) administered over three
      consecutive days based on larvae per gramme of faeces (LPG), measured on days 28
      +/- 2 following treatment and compared to counts on days -6 to -2. In total 24
      cats treated either with Advocate (n = 12) or with Panacur (n = 12) were
      included. Mean LPG postbaseline (days 28 +/- 2) were low in both treatment
      groups, i.e., 0 LPG for Advocate and 1.3 LPG for Panacur. Reduction of post
      baseline larval counts showed Advocate (100% reduction) to be superior in
      efficacy compared to the control product (99.29% reduction). No treated animals
      showed adverse events. This trial demonstrated that both Advocate spot-on
      formulation and Panacur oral paste are safe and effective in the treatment of
      aelurostrongylosis in cats. Future practical perspectives in feline medicine and
      the major advantages of the spot-on product compared to the oral paste are
      discussed.

PMID- 19575227
TI  - Current surveys on the prevalence and distribution of Dirofilaria spp. in dogs in
      Germany.
AB  - The Central Upper-Rhine (Baden-Wurttemberg, Germany) is one of the warmest
      regions in Germany and also harbours abundant numbers of mosquitoes. Case reports
      on presumably autochthonous occurrence of Dirofilaria spp. were reported
      previously and were a reason for a further investigation into the occurrence of
      vector-borne pathogens. For this purpose, 44 hunting dogs from the Central Upper
      Rhine region were tested between 4(th) and 29(th) June 2007. The blood samples
      were tested using the Knott's test and IDEXX SNAP 4Dx test. The Knott's test
      revealed unsheathed microfilaria identified as Dirofilaria repens by PCR in 3
      dogs with no history of travelling (6.8%; 95% CI: 2.4-18.2%). The seroprevalence
      for Anaplasma phagocytophilum was 43.2% (95% CI: 29.7-57.8%), but only 4.5% (95%
      CI: 1.3-15.1%) for antibodies to Borrelia C6 peptide. Dirofilaria immitis antigen
      was not detected in any of the samples. A further 288 blood samples from non
      hunting companion dogs of the Central Upper-Rhine region were tested negative for
      heartworm antigen between February and August 2007.

PMID- 19575228
TI  - Treatment and prevention of vertical transmission of Toxocara cati in cats with
      an emodepside/praziquantel spot-on formulation.
AB  - This study aimed to determine the efficacy of emodepside 2.14%/praziquantel 8.58%
      topical solution (Profender, Bayer) in the prevention and treatment of lactogenic
      Toxocara cati infections. Eight pregnant cats were orally infected with T. cati
      eggs during late pregnancy. Four queens were treated on day 60 post conception
      and four queens were left untreated. The kittens of two untreated queens were
      treated 28 days after birth. The two other negative control litters were left
      untreated. The efficacy of emodepside was determined by faecal egg counts. While
      faecal samples of queens and litters in the control group became positive for T.
      cati, egg shedding was completely prevented in all four treated queens, in their
      litters and in the kittens from the two litters which were treated four weeks
      after birth. The untreated mothers of the latter stayed also coproscopically
      negative, which might be explained by an oral uptake of emodepside through
      grooming. The treatment was well tolerated by pregnant queens as well as by four
      weeks-old kittens.To our knowledge, this is the first publication that focuses on
      the prevention of lactogenic transmission of T. cati.

PMID- 19575229
TI  - Efficacy and safety of emodepside 2.1%/praziquantel 8.6% spot-on formulation in
      the treatment of feline aelurostrongylosis.
AB  - The objective of the present study was to evaluate the efficacy and safety of the
      antiparasitic spot-on formulation containing emodepside 2.1%/praziquantel 8.6%
      (Profender, Bayer) in the treatment of natural feline infection with the lungworm
      Aelurostrongylus abstrusus (Nematoda, Strongylida). Efficacy of Profender given
      once at the licensed dose was tested in comparison to a control oral formulation
      containing fenbendazole 18.75% (Panacur, Intervet) given over three consecutive
      days at the licensed dose. Efficacy assessment was based on larvae per gramme of
      faeces (LPG) counts, measured on days 28 +/- 2 following treatment and compared
      to counts on days -6 to -2. In total 24 cats treated either with Profender (n =
      12) or with Panacur (n = 12) were included in the assessment of efficacy and
      safety. Mean LPG post-baseline counts (days 28 +/- 2) were 1.3 LPG for both
      Profender and Panacur, demonstrating similar efficacy of 99.38% for Profender and
      99.29% for the control product. No treated animals showed adverse events. This
      trial demonstrated that both Profender spot-on formulation and oral paste Panacur
      are safe and effective in the treatment of aelurotrongylosis in cats. Future
      practical perspectives in feline medicine and the major advantages of the spot-on
      product compared to the oral paste are discussed.

PMID- 19575230
TI  - The putative cyclooctadepsipeptide receptor depsiphilin of the canine hookworm
      Ancylostoma caninum.
AB  - The G-Protein-coupled receptor Hc110-R of Haemonchus contortus and its orthologue
      in Caenorhabditis elegans, the latrophilin-like protein 1 (LAT-1), were shown to
      play a role in the mode of action of the new anthelmintic compound emodepside. C.
      elegans LAT-1 knockout mutants showed a decreased paralysing effect of emodepside
      on the pharyngeal muscle. In the present study, the LAT-1 orthologue in the
      canine hookworm Ancylostoma caninum was identified and named depsiphilin. To
      obtain more information about the regulation of this receptor and to facilitate
      phylogenetic and evolutionary analyses of parasitic nematode genes, the genomic
      structure of A. caninum depsiphilin was investigated. High consistency regarding
      the position of introns in comparison to C. elegans LAT-1 was observed, providing
      indication of the same origin of the genes. With a view to possible differences
      in efficacy of emodepside on different developmental stages, we analysed the
      transcript level of A. caninum depsiphilin in eggs, L1, L3, male and female adult
      worms using quantitative real-time PCR. Depsiphilin is transcribed in all five
      examined stages, but we found a significantly lower transcript level in third
      stage larvae. A correlation between these findings and a reduced emodepside
      activity remains to be investigated.

PMID- 19575231
TI  - Occurrence of Dirofilaria immitis and tick-borne infections caused by Anaplasma
      phagocytophilum, Borrelia burgdorferi sensu lato and Ehrlichia canis in domestic
      dogs in France: results of a countrywide serologic survey.
AB  - The occurrence of Dirofilaria immitis antigen and antibodies against tick-borne
      pathogens in French dogs has been analysed based on 1,050 blood samples. Serum
      samples of 919 dogs (group A) were sent for a variety of diagnostic
      investigations, further 131 dogs (group B) were tested for a tentative diagnosis
      of heartworm disease. All samples were tested for D. immitis antigen. Samples in
      group A were also tested for specific antibodies against three tick-borne
      pathogens (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato and
      Ehrlichia canis). Results were plotted in geographical maps. Occurrence of D.
      immitis antigen in group A (0.22%; 95 % CI: 0.03-0.78%) was significantly lower
      (p < 0.0001) than in group B (6.87%; 95% CI: 3.19-12.64%). Heartworm infections
      in both groups were regionally restricted to the areas of Bouches-du-Rhone in the
      South of France and Corsica. In group A, the calculated seroprevalence was 2.72%
      (95% CI: 1.77-3.99%) for A. phagocytophilum, 1.09% (95% CI: 0.52-1.99%) for B.
      burgdorferi and 0.33% (95% CI: 0.07-0.95%) for E. canis with a distribution of
      the positive cases throughout the country. This study represents the first data
      of A. phagocytophilum seroprevalence in the French dog population.

PMID- 19575232
TI  - Comparative efficacy and safety of two treatment regimens with a topically
      applied combination of imidacloprid and moxidectin (Advocate) against generalised
      demodicosis in dogs.
AB  - This laboratory study compared the efficacy of two treatment regimens using an
      imidacloprid (10%)/moxidectin (2.5%) topical formulation (Advocate, Bayer) on
      dogs with generalised demodicosis. Sixteen dogs were randomly allocated to two
      equal groups. One group was treated at 28-day intervals for 12 weeks and the
      second group at weekly intervals for 15 weeks. Mite numbers were estimated and
      demodectic lesions were evaluated on each dog before treatment and at
      approximately 28-day intervals thereafter. Consistently greater reduction in mite
      numbers was recorded for the weekly treatment regimen. Dogs treated at weekly
      intervals exhibited markedly fewer clinical signs and greater hair regrowth and
      weight gain than those treated at 28-day intervals. To assess the safety of a
      weekly treatment interval in dogs, a study was done in which the investigational
      compound was administered at weekly intervals at five times the recommended dose
      for a period of 16 consecutive weeks. Apart from transient erythema at the site
      of administration in one dog and scaliness of the skin in another, no clinical
      signs of toxicity could be observed. Assessment of 27 blood parameters indicated
      that only basophils were outside the reference values on days +13 and +69, during
      the safety trial period.

PMID- 19575233
TI  - Treatment of naturally occurring, asymptomatic Giardia sp. in dogs with Drontal
      Plus flavour tablets.
AB  - The administration of three consecutive daily doses of the recommended 1x dose of
      Drontal Plus flavour tablets (Bayer) was examined for its effect on Giardia sp.
      cyst-shedding in 7 treated and 7 untreated random-source dogs. Dogs were treated
      on study days 0, 1 and 2. Cysts were quantified using direct immunofluorescent
      labelling on days -7, -5, -3 and -2, and daily from day 1 through 11. Three
      treated dogs never shed cysts again during the study, one shed again only on day
      4, and the remaining three dogs started to shed again on days 8, 9 and 11. The
      mean numbers of cysts per gramme in the faeces of the treated dogs were
      significantly reduced (t-tests using log(10)(counts)) on days 1 and 2 (geometric
      means: controls = 447,000; treated = 1,050; p = 0.004) and days 3 to 8 (geometric
      means: controls = 23,400; treated 5.0; p < 0.001). Four controls that had been
      consistently positive, changed to negative status on day 11, and thus, on the
      final day of the trial, there were only three positive control and three positive
      treated dogs. Three consecutive days of treatment with Drontal Plus flavour
      tablets halted Giardia sp. cyst shedding by dogs. But starting six days post
      third treatment, some of the dogs started shedding cysts again. Since the
      prepatent period of Giardia sp. can be as short as 4 days, shedding of Giardia
      sp. cysts 6 days after treatment could be caused by a reinfection.

PMID- 19575234
TI  - Synergistic effect of febantel and pyrantel embonate in elimination of Giardia in
      a gerbil model.
AB  - The objectives of the study were to determine the optimal dose of febantel,
      pyrantel embonate and a combination of febantel/pyrantel embonate required to
      effectively treat Giardia in a gerbil model and to determine if there is a
      synergistic effect with the two drugs. SPF gerbils were infected by oral
      inoculation with 105 Giardia duodenalis trophozoites (day 0). On days 5 to 7,
      animals (n = 6) were treated once daily via oral gavage with febantel, pyrantel
      embonate, febantel and pyrantel embonate, metronidazole or placebo. Gerbils were
      euthanised 24 hours after last treatment and duodenal trophozoites were
      enumerated on a haemocytometer to obtain a concentration of trophozoites/ cm of
      gut. Febantel alone, effectively eliminated Giardia trophozoites at 160 and 80
      mg/kg. Pyrantel embonate did not eliminate Giardia from the animals but
      significantly reduced parasite counts at all dosages. Febantel combined with
      pyrantel embonate effectively eliminated Giardia trophozoites at 160, 80 and 40
      mg/kg. Metronidazole did not eliminate Giardia trophozoites from the gut. All
      placebo-treated animals were heavily infected with Giardia trophozoites. It can
      be concluded that febantel is more effective in elimination of Giardia infections
      when combined with pyrantel embonate compared to the agents used alone.

PMID- 19575235
TI  - Study of the comparative efficacy of toltrazuril and diclazuril against ovine
      coccidiosis in housed lambs.
AB  - A blinded, controlled and randomised field study was conducted on a sheep farm
      with a known history of coccidiosis and a high prevalence mainly of the
      pathogenic coccidium Eimeria ovinoidalis. The efficacy of treatment with
      toltrazuril (Baycox 5% suspension) against natural infections with Eimeria
      crandallis and/or Eimeria ovinoidalis in housed lambs was investigated in
      comparison with diclazuril and untreated controls. Both drugs were administered
      either metaphylactically (i.e., in the prepatency of Eimeria spp.) or
      therapeutically (after onset of oocyst excretion). A total of 145 animals aged 1
      to 5 days at the start of the study were included. Examination of faecal samples
      was performed every second day between days 13 and 49 of the study. The
      assessment of treatment efficacy was based mainly on total oocyst excretion and
      the number of E. crandallis and E. ovinoidalis oocysts (OPG) shed throughout the
      study. Oocyst excretion was reduced significantly in both groups treated with
      toltrazuril compared with the untreated control group and with both diclazuril
      treated groups. The most prevalent and most severe diarrhoea was observed in the
      untreated control group. In this study, toltrazuril proved to be highly effective
      in controlling ovine coccidiosis both metaphylactically and therapeutically. The
      efficacy of toltrazuril was significantly higher than the efficacy of the control
      substance with regard to the duration and amount of oocyst excretion, both for
      the comparison of metaphylactic as well as therapeutic treatment.

PMID- 19575236
TI  - Porcine coccidiosis--investigations on the cellular immune response against
      Isospora suis.
AB  - Porcine neonatal coccidiosis is caused by the protozoan Isospora suis and affects
      mainly piglets in the first three weeks of life. High morbidity with diarrhoea
      and reduced weight gain lead to economic losses, affecting pig-breeding
      worldwide. Infection causes damage of the mucosal surface in the jejunum and
      ileum and transient non-haemorrhagic diarrhoea. Secondary infections with other
      enteric pathogens may lead to increased mortality. Despite its economic and
      veterinary importance, the immunology of porcine isosporosis is still poorly
      understood. A striking feature of the infection is the rapidly increasing age
      resistance prohibiting the development of clinical disease in piglets older than
      3-4 weeks irrespective of the immune status. It can be hypothesised that the
      development of the innate immune system in the first weeks of life and
      subsequently its interplay with the adaptive immune system is closely related to
      this phenomenon. Infections with I. suis induce migration of TcR-gammadelta(+)
      cells to the gut during primary infection and lead to induction of IFN-gamma
      production by TcR-gammadelta(+) cells and CD4(+) T-helper cells in blood and
      various lymphoid tissues. Like in other coccidial infections both innate as well
      as adaptive response mechanisms are activated during infection. They might be
      both not completely developed in the first weeks of life and therefore leaving a
      time frame for successful infection.

PMID- 19575237
TI  - Age, not infection dose, determines the outcome of Isospora suis infections in
      suckling piglets.
AB  - Data from 13 trials involving 124 suckling piglets experimentally infected with
      Isospora suis were evaluated for the effects of infection dose and age on the
      clinical and parasitological outcome of infection in four different models,
      infections with 1,000 oocysts on the 1(st) day of life (d.o.l.) (model 1; 9
      piglets/3 litters), 1,000 oocysts on the 4(th) d.o.l. (model 2; 25 piglets/11
      litters), 1,500 oocysts on the 4(th) d.o.l. (model 3; 40 piglets/20 litters) and
      10,000 oocysts on the 4(th) d.o.l. (model 4; 50 animals/10 litters). Weights were
      determined on the day of birth and in weekly intervals. Faecal consistency and
      quantitative oocysts excretion were evaluated for 2 weeks starting 4 days after
      infection (d.p.i.). The weight gain depression was most noticeable in model 2
      (infection on the 1(st) d.o.l.), where animals only gained 2.08 x their birth
      weight until the 22(nd) d.o.l., compared to 2.31-2.52 x in the other groups. This
      correlated with the occurrence of watery diarrhoea which was found in 37 % of the
      samples in the acute phase (4-11 d.p.i.) in model 2 but only in 12-20 % of the
      samples in the other models. Median oocyst excretion peaked earlier in the models
      with higher infection doses but reached the highest values in model 2 (early
      infection). As in previous studies, this cross-sectional analysis of a larger
      number of animals confirms the influence of age on the outcome of isosporosis in
      suckling piglets, stressing the need to control the infection at an early life
      phase.

PMID- 19575238
TI  - NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis
      susceptibility in African-Americans.
AB  - Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed
      progressing to active TB disease. Studies in mice and humans indicate that the
      inducible nitric oxide synthase (iNOS) molecule plays an important role in immune
      response to TB. A mixed case-control association study of individuals with TB,
      relatives, or close contact controls was performed in 726 individuals (279 case
      and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty
      nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for
      single SNP, haplotype, and multilocus interaction analyses with other typed
      candidate genes using generalized estimating equations. In African-Americans, ten
      NOS2A SNPs were associated with TB. The strongest associations were observed at
      rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p =
      0.003) and rs7215373 (OR = 1.67, 95% CI [1.17-2.37], p = 0.004), both of which
      passed a false discovery rate correction for multiple comparisons (q* = 0.20).
      The strongest gene-gene interactions were observed between NOS2A rs2248814 and
      IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p =
      0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other
      NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were
      observed in Caucasians. These results suggest that NOS2A variants may contribute
      to TB susceptibility, particularly in individuals of African descent, and may act
      synergistically with SNPs in TLR4 and IFNGR1.

PMID- 19575239
TI  - Are tortoises important seed dispersers in Amazonian forests?
AB  - According to most studies on seed dispersal in tropical forests, mammals and
      birds are considered the main dispersal agents and the role played by other
      animal groups remains poorly explored. We investigate qualitative and
      quantitative components of the role played by the tortoise Chelonoidis
      denticulata in seed dispersal in southeastern Amazon, and the influence of
      seasonal variation in tortoise movement patterns on resulting seed shadows. Seed
      shadows produced by this tortoise were estimated by combining information on seed
      passage times through their digestive tract, which varied from 3 to 17 days, with
      a robust dataset on movements obtained from 18 adult C. denticulata monitored
      with radio transmitters and spoon-and-line tracking devices. A total of 4,206
      seeds were found in 94 collected feces, belonging to 50 seed morphotypes of, at
      least, 25 plant genera. Very low rates of damage to the external structure of the
      ingested seeds were observed. Additionally, results of germination trials
      suggested that passage of seeds through C. denticulata's digestive tract does not
      seem to negatively affect seed germination. The estimated seed shadows are likely
      to contribute significantly to the dispersal of seeds away from parent plants.
      During the dry season seeds were dispersed, on average, 174.1 m away from the
      location of fruit ingestion; during the rainy season, this mean dispersal
      distance increased to 276.7 m. Our results suggest that C. denticulata plays an
      important role in seed dispersal in Amazonian forests and highlight the influence
      of seasonal changes in movements on the resulting seed shadows.

PMID- 19575240
TI  - Low-dose pulse methylprednisolone followed by short-term combination therapy and
      tonsillectomy for childhood IgA nephropathy.

PMID- 19575241
TI  - Land use practices and ectomycorrhizal fungal communities from oak woodlands
      dominated by Quercus suber L. considering drought scenarios.
AB  - Oak woodlands in the Mediterranean basin have been traditionally converted into
      agro-silvo-pastoral systems and exemplified sustainable land use in Europe. In
      Portugal, in line with the trend of other European countries, profound changes in
      management options during the twentieth century have led to landscape
      simplification. Landscapes are dynamic and the knowledge of future management
      planning combining biological conservation and soil productivity is needed,
      especially under the actual scenarios of drought and increasing evidence of heavy
      oak mortality. We examined the ectomycorrhizal (ECM) fungal community associated
      with cork oak in managed oak woodlands (called montado) under different land use
      practices, during summer. ECM fungal richness and abundance were assessed in 15
      stands established in nine montados located in the Alentejo region (southern
      Portugal), using morphotyping and ITS rDNA analysis. Parameters related to the
      montados landscape characteristics, land use history over the last 25 years,
      climatic and edaphic conditions were taken into account. Fifty-five ECM fungal
      taxa corresponding to the most abundant fungal symbionts were distinguished on
      cork oak roots. Cenococcum geophilum and the families Russulaceae and
      Thelephoraceae explained 56% of the whole ECM fungal community; other groups were
      represented among the community: Cortinariaceae, Boletaceae, Amanita, Genea,
      Pisolithus, Scleroderma, and Tuber. There were pronounced differences in ECM
      fungal community structure among the 15 montados stands: C. geophilum was the
      only species common to all stands, tomentelloid and russuloid species were
      detected in 87-93% of the stands, Cortinariaceae was detected in 60% of the
      stands, and the other groups were more unequally distributed. Ordination analysis
      revealed that ECM fungal richness was positively correlated with the silvo
      pastoral exploitation regime and low mortality of cork oak, while ECM fungal
      abundance was positively correlated with extensive agro-silvo-pastoral
      exploitation under a traditional 9-year rotation cultivation system and recent
      soil tillage. The effects of land use on the ECM fungal community and its
      implications in different scenarios of landscape management options, oak
      mortality, and global warming are discussed.

PMID- 19575242
TI  - Percutaneous approach to the upper thoracic spine: optimal patient positioning.
AB  - Percutaneous access to the upper thoracic vertebrae under fluoroscopic guidance
      is challenging. We describe our positioning technique facilitating optimal
      visualisation of the high thoracic vertebrae in the prone position. This allows
      safe practice of kyphoplasty, vertebroplasty and biopsy throughout the upper
      thoracic spine.

PMID- 19575243
TI  - Management of pulmonary cement embolism after percutaneous vertebroplasty and
      kyphoplasty: a systematic review of the literature.
AB  - Balloon kyphoplasty and percutaneous vertebroplasty are relatively recent
      procedures in the treatment of painful vertebral fractures. There are, however,
      still some uncertainties about the incidence and treatment strategies of
      pulmonary cement embolisms (PCE). In order to work out a treatment strategy for
      the management of this complication, we performed a review of the literature. The
      results show that there is no clear diagnostic or treatment standard for PCE. The
      literature research revealed that the risk of a pulmonary embolism ranges from
      3.5 to 23% for osteoporotic fractures. In cases of asymptomatic patients with
      peripheral PCE we recommend no treatment besides clinical follow-up; in cases of
      symptomatic or central embolisms, however, we recommend to proceed according to
      the guidelines regarding the treatment of thrombotic pulmonary embolisms, which
      includes initial heparinization and a following 6-month coumarin therapy. In
      order to avoid any types of embolisms, both procedures should only be performed
      by experienced surgeons after critical determination of the indications.

PMID- 19575246
TI  - Density functional computational studies on (E)-2-[(2-Hydroxy-5-nitrophenyl)
      iminiomethyl]-4-nitrophenolate.
AB  - Density functional calculations of the structure, atomic charges, molecular
      electrostatic potential and thermodynamic functions have been performed at
      B3LYP/6-31G(d,p) level of theory for the title compound (E)-2-[(2-hydroxy-5
      nitrophenyl)-iminiomethyl]-4-nitrophenolate. The results show that the phenolate
      oxygen atom and all of the nitro group oxygen atoms have bigger negative charges,
      and the coordination ability of these atoms differs in different solvents. The
      energetic behavior of the title compound in solvent media has been examined using
      B3LYP method with the 6-31G(d,p) basis set by applying the Onsager method and the
      isodensity polarized continuum model (IPCM). The results obtained with these
      methods reveal that the IPCM method yielded a more stable structure than
      Onsager's method. In addition, natural bond orbital and frontier molecular
      orbital analysis of the title compound were performed using the B3LYP/6-31G(d,p)
      method.

PMID- 19575245
TI  - Interaction of selected divalent metal ions with human ataxin-3 Q36.
AB  - The mode of interaction of ataxin-3 Q36 (AT-3 Q36) with selected endogenous and
      exogenous metal ions, namely, Zn(2+), Cu(2+), Ni(2+), and Cd(2+), was examined.
      Metal-ion-induced structural changes of the protein were monitored by
      fluorescence as well as Fourier transform Raman spectroscopy. We found that the
      cations tested lead to a decrease in alpha-helical content and a concurrent
      increase in beta-sheet as well as undefined (beta-turn and random-coil)
      structures. The most evident effect was observed for copper and nickel cations.
      After titration with these cations, the AT3 Q36 secondary structure content (27%
      alpha-helices in the presence of either ion, 31 and 27% beta-sheets for Cu(2+)
      and Ni(2+), respectively) was similar to that observed for the aggregated form of
      the protein (27% alpha-helices, 36% beta-sheets). Using the 1-anilinonaphthalene
      8-sulfonate hydrophobic fluorescence probe, we showed that the presence of the
      metal ions tested led to the formation of solvent-exposed hydrophobic patches of
      AT-3 Q36, and that such an effect decreased with increasing ionic radius.

PMID- 19575244
TI  - In vitro study of accuracy of cervical pedicle screw insertion using an
      electronic conductivity device (ATPS part III).
AB  - Reconstruction of the highly unstable, anteriorly decompressed cervical spine
      poses biomechanical challenges to current stabilization strategies, including
      circumferential instrumented fusion, to prevent failure. To avoid secondary
      posterior surgery, particularly in the elderly population, while increasing
      primary construct rigidity of anterior-only reconstructions, the authors
      introduced the concept of anterior transpedicular screw (ATPS) fixation and
      plating. We demonstrated its morphological feasibility, its superior
      biomechanical pull-out characteristics compared with vertebral body screws and
      the accuracy of inserting ATPS using a manual fluoroscopically assisted
      technique. Although accuracy was high, showing non-critical breaches in the axial
      and sagittal plane in 78 and 96%, further research was indicated refining
      technique and increasing accuracy. In light of first clinical case series, the
      authors analyzed the impact of using an electronic conductivity device (ECD,
      PediGuard) on the accuracy of ATPS insertion. As there exist only experiences in
      thoracolumbar surgery the versatility of the ECD was also assessed for posterior
      cervical pedicle screw fixation (pCPS). 30 ATPS and 30 pCPS were inserted
      alternately into the C3-T1 vertebra of five fresh-frozen specimen. Fluoroscopic
      assistance was only used for the entry point selection, pedicle tract preparation
      was done using the ECD. Preoperative CT scans were assessed for sclerosis at the
      pedicle entrance or core, and vertebrae with dense pedicles were excluded. Pre-
      and postoperative reconstructed CT scans were analyzed for pedicle screw
      positions according to a previously established grading system. Statistical
      analysis revealed an astonishingly high accuracy for the ATPS group with no
      critical screw position (0%) in axial or sagittal plane. In the pCPS group, 88.9%
      of screws inserted showed non-critical screw position, while 11.1% showed
      critical pedicle perforations. The usage of an ECD for posterior and anterior
      pedicle screw tract preparation with the exclusion of dense cortical pedicles was
      shown to be a successful and clinically sound concept with high-accuracy rates
      for ATPS and pCPS. In concert with fluoroscopic guidance and pedicle axis views,
      application of an ECD and exclusion of dense cortical pedicles might increase
      comfort and safety with the clinical use of pCPS. In addition, we presented a
      reasonable laboratory setting for the clinical introduction of an ATPS-plate
      system.

PMID- 19575247
TI  - Mg-Al layered double hydroxide intercalated with porphyrin anions: molecular
      simulations and experiments.
AB  - Molecular modeling in combination with powder X-ray diffraction (XRD) provided
      new information on the organization of the interlayer space of Mg-Al layered
      double hydroxide (LDH) containing intercalated porphyrin anions [5,10,15,20
      tetrakis(4-sulfonatophenyl)porphyrin (TPPS)]. Anion-exchange and rehydration
      procedures were used for the preparation of TPPS-containing LDH with an Mg/Al
      molar ratio of 2. Molecular modeling was carried out in the Cerius(2) and
      Materials Studio modeling environment. Three types of models were created in
      order to simulate the experimental XRD patterns of LDH intercalates with a TPPS
      loading of 70-80% with respect to the theoretical anion exchange capacity (AEC).
      The models represent single-phase systems with a 100% TPPS loading in the
      interlayer space (Type 1) and models represent the coexistence of two phases
      corresponding to the total exchange from 75 to 92% (Type 2). To cover other
      possible arrangements, models with the coexistence of both TPPS and NO(3)(-)
      anions in the same interlayer space were calculated (Type 3). The models are
      described and compared with experimental data. In all cases, guest TPPS anions
      are tilted with respect to the hydroxide layers, and are horizontally shifted to
      each other by up to one-half of the TPPS diameter. According to the energy
      characteristics and simulated XRD, the most probable arrangement is of Type 2,
      where some layers are saturated with TPPS anions and others are filled with
      original NO(3)(-) anions.

PMID- 19575248
TI  - Combination antibiotic susceptibility of biofilm-grown Burkholderia cepacia and
      Pseudomonas aeruginosa isolated from patients with pulmonary exacerbations of
      cystic fibrosis.
AB  - We identified double and triple antibiotic combinations effective against biofilm
      grown Burkholderia cepacia and Pseudomonas aeruginosa sampled from cystic
      fibrosis (CF) patients undergoing acute pulmonary exacerbations. Sputum bacteria
      from 110 CF patients were grown as biofilms. Combination antibiotic
      susceptibility testing was used to test 94 double and triple antibiotic
      combinations. Biofilm-grown bacterial isolates were less susceptible to
      antibiotic combinations compared to the same bacterial isolates grown
      planktonically (P < 0.001). Fifty-nine percent of biofilm-grown B. cepacia
      isolates and 29% of P. aeruginosa isolates were resistant to all double
      antibiotic combinations tested. Triple antibiotic combinations were more
      effective than double antibiotic combinations against biofilms (P < 0.0001). For
      P. aeruginosa biofilms, the addition of azithromycin or rifampin to otherwise
      effective antibiotic combinations was frequently associated with antagonism.
      Bacterial biofilms of CF organisms are highly resistant to antibiotics. This
      study identified potentially effective antibiotic combinations to guide the
      empirical treatment of CF pulmonary exacerbations.

PMID- 19575249
TI  - Distribution of pathogenic Yersinia enterocolitica in China.
AB  - Yersinia enterocolitica (1,295 strains) was isolated from diarrhea patients,
      livestock, poultry, wild animals, insect vectors, food, and the environment. They
      were studied for epidemiology distribution using bacterial biochemical metabolism
      tests, their virulence genes, and pulsed-field gel electrophoresis (PFGE) sub
      typing. The data showed that 416 of the 1,295 strains were pathogenic, where the
      pathogenic Chinese isolates were of serotypes O:3 and O:9. These two serotypes
      were found in livestock and poultry, with swine serving as the major reservoir.
      The geographic distribution of pathogenic isolates was significantly different,
      where most of the strains were isolated from the cold northern areas, whereas
      some serotype O:3 strains were recovered from the warm southern areas. By the
      analysis of the data of the Ningxia Hui Autonomous Region, we find the phenomenon
      of 'concentric circle distribution' around animal reservoirs and human
      habitation. The clustering of PFGE showed that the patterns of the pathogenic
      strains isolated from diarrhea patients were identical compared to those from the
      animals in the same area, thus, suggesting that the human infection originated
      from the animals.

PMID- 19575250
TI  - Genomics in cereals: from genome-wide conserved orthologous set (COS) sequences
      to candidate genes for trait dissection.
AB  - Recent updates in comparative genomics among cereals have provided the
      opportunity to identify conserved orthologous set (COS) DNA sequences for cross
      genome map-based cloning of candidate genes underpinning quantitative traits. New
      tools are described that are applicable to any cereal genome of interest, namely,
      alignment criterion for orthologous couples identification, as well as the Intron
      Spanning Marker software to automatically select intron-spanning primer pairs. In
      order to test the software, it was applied to the bread wheat genome, and 695 COS
      markers were assigned to 1,535 wheat loci (on average one marker/2.6 cM) based on
      827 robust rice-wheat orthologs. Furthermore, 31 of the 695 COS markers were
      selected to fine map a pentosan viscosity quantitative trait loci (QTL) on wheat
      chromosome 7A. Among the 31 COS markers, 14 (45%) were polymorphic between the
      parental lines and 12 were mapped within the QTL confidence interval with one
      marker every 0.6 cM defining candidate genes among the rice orthologous region.

PMID- 19575251
TI  - Theoretical study of a membrane channel gated by ATP.
AB  - We study channel transport across biomembranes. We propose a model that couples
      the diffusive dynamics with the gating process via a two-state ratchet mechanism.
      This gating process is governed by ATP binding and hydrolysis, and the process
      exhibits Michaelis-Menten enzymatic kinetics. The particle flow and permeability
      of the channel are studied both analytically and numerically in the steady-state
      regime, while working between fixed concentrations. The results are compared with
      simpler models and with experimental data. Also, a simulation framework, that
      allows high flexibility in parameter exploration, is introduced.

PMID- 19575252
TI  - The state of ambient air quality in Pakistan--a review.
AB  - BACKGROUND AND PURPOSE: Pakistan, during the last decade, has seen an extensive
      escalation in population growth, urbanization, and industrialization, together
      with a great increase in motorization and energy use. As a result, a substantial
      rise has taken place in the types and number of emission sources of various air
      pollutants. However, due to the lack of air quality management capabilities, the
      country is suffering from deterioration of air quality. Evidence from various
      governmental organizations and international bodies has indicated that air
      pollution is a significant risk to the environment, quality of life, and health
      of the population. The Government has taken positive steps toward air quality
      management in the form of the Pakistan Clean Air Program and has recently
      established a small number of continuous monitoring stations. However, ambient
      air quality standards have not yet been established. This paper reviews the data
      being available on the criteria air pollutants: particulate matter (PM), sulfur
      dioxide, ozone, carbon monoxide, nitrogen dioxide, and lead. METHODS: Air
      pollution studies in Pakistan published in both scientific journals and by the
      Government have been reviewed and the reported concentrations of PM, SO(2), O(3),
      CO, NO(2), and Pb collated. A comparison of the levels of these air pollutants
      with the World Health Organization air quality guidelines was carried out.
      RESULTS: Particulate matter was the most serious air pollutant in the country.
      NO(2) has emerged as the second high-risk pollutant. The reported levels of PM,
      SO(2), CO, NO(2), and Pb were many times higher than the World Health
      Organization air quality guidelines. Only O(3) concentrations were below the
      guidelines. CONCLUSIONS: The current state of air quality calls for immediate
      action to tackle the poor air quality. The establishment of ambient air quality
      standards, an extension of the continuous monitoring sites, and the development
      of emission control strategies are essential.

PMID- 19575253
TI  - Development of a high-density assay for long-chain fatty acyl-CoA elongases.
AB  - We established a convenient assay method for measuring elongation of very long
      chain fatty acids (ELOVLs) using a Unifilter-96 GF/C plate. The Unifilter GF/C
      plate preferentially interacts with hydrophobic end products of ELOVLs (i.e.,
      long chain fatty acid), with minimal malonyl-CoA (C2 unit donor for fatty acid
      elongation) interaction. This new method results in the quick separation and
      detection of [(14)C] incorporated end products (e.g., [(14)C] palmitoyl-CoA) from
      reaction mixtures containing excessive amounts of [(14)C] malonyl-CoA. In the
      Unifilter-96 GF/C plate assay, recombinantly expressed human ELOVLs (i.e.,
      ELOVL1,-2,-3,-5 and -6) displayed appreciable assay windows (>2-fold vs. mock
      transfected control), enabling us to conduct comprehensive substrate profiling of
      ELOVLs. The substrate concentration profile of ELOVL6 in the Unifilter-96 GF/C
      plate assay is consistent with that obtained from the conventional liquid
      extraction method, thus, supporting the reliability of the Unifilter-96 GF/C
      plate assay. We then examined the substrate specificities of ELOVLs in a
      comprehensive fashion. As previously reported, ELOVL1, -3 and -6 preferably
      elongated the saturated fatty acyl-CoAs while ELOVL2 and ELOVL5 preferentially
      elongated the polyunsaturated fatty acyl-CoAs. This further confirms the
      Unifilter-96 GF/C plate assay reliability. Taken together, our newly developed
      assay provides a convenient and comprehensive assay platform for ELOVLs, allowing
      investigators to conduct high density screening and characterization of ELOVLs
      chemical tools.

PMID- 19575254
TI  - [Many active ingredients--higher compatibility risks].

PMID- 19575255
TI  - [Dermatosurgery].

PMID- 19575256
TI  - [Histopathology of gestational trophoblastic disease. An update].
AB  - The differential diagnosis of villous forms of gestational trophoblastic disease
      (GTD) includes hydropic abortion, complete and partial hytatidiform mole and
      placental mesenchymal dysplasia. In addition to histologic criteria, p57(KIP2)
      immunohistochemistry might be helpful. Choriocarcinoma represents the most
      immature form of GTD. This and downregulation of HSP-27 might contribute to the
      high chemosensitivity, compared to placental site (PSTT) and epitheloid
      trophoblastic tumor (ETT). Within the differential diagnosis of the non-villous
      forms of GTD an algorithmic approach of immunohistochemistry is very helpful.
      With an incidence of 1.6% of all abortions within the first trimester the
      exaggerated placental site reaction (EPS) is rare. There is no molecular
      indication that the EPS represents a precursor lesion of PSTT. The morphologic
      prediction of the behaviour of PSTT is not well established. Factors which might
      be associated with adverse outcome are age >35 years, interval since last
      pregnancy >2 years, growth outside the uterus, deep myometrial invasion,
      destructive growth, extensive coagulative necrosis, presence of cells with clear
      cytoplasm, high mitotic rate and a Ki-67 labeling index >50%. Recent molecular
      data suggest a neoplastic transformation of (cyto-) trophoblastic stem cells,
      within the pathogenesis of (non-villous) GTD. The detection of target molecules
      for a targeted therapy is currently irrelevant.

PMID- 19575257
TI  - [Appointment of Professor Burkhard Helpap as an honorary member of the Federation
      of German pathology 24 April 2009].

PMID- 19575258
TI  - Effects of galacto-oligosaccharide ingestion on the mucosa-associated mucins and
      sucrase activity in the small intestine of mice.
AB  - BACKGROUND: Galacto-oligosaccharides (GOS) are non-digestible oligosaccharides
      with short galactosyl chain units produced by lactose fermentation which are
      considered as prebiotics. Only few studies have investigated the effects of GOS
      medium-term ingestion on the small intestinal epithelium characteristics. AIM OF
      THE STUDY: In this study, we evaluated the consequences of GOS ingestion on small
      intestinal mucosal morphology, on brush-border membrane enzyme activities and on
      mucin content in BALB/c mice. METHODS: Mice received the experimental diets for 4
      weeks and then the small intestine was collected to measure sucrase, lactase and
      alkaline phosphatase activities, to study the villus heights in the jejunum
      mucosa and to determine mucosal mucin content as well as MUC-2 and MUC-4 mRNAs
      expression by qRT-PCR. RESULTS: Our results showed that GOS has no detectable
      effect on the intestine villus height but increased the total protein content by
      twofold. Sucrase activity was significantly increased in the intestinal mucosa
      recovered from animals fed the GOS diet without any detectable modification of
      lactase and phosphatase activities. Interestingly, GOS was also able to increase
      sucrase activity in cultured Caco-2 cells raising the view that they likely act
      directly on these cells. Furthermore, GOS was found to markedly increase O-linked
      glycoproteins associated with the intestinal mucosa without modifying MUC-2, MUC
      4 mRNAs expression. Lastly, TNF-alpha mRNA expression was also not modified after
      GOS ingestion. CONCLUSIONS: These results suggest that, in BALB/c mice, 4-week
      GOS ingestion is able to increase the small intestinal mucosa-associated mucin
      content and enterocyte-associated sucrase activity without modifying villus
      height.

PMID- 19575260
TI  - Is there a difference in gastric emptying between Parkinson's disease patients
      under long-term L-dopa therapy with and without motor fluctuations? An analysis
      using the 13C-acetate breath test.
AB  - The mechanism underlying the motor fluctuations that develop after long-term L
      dopa therapy is not fully known. It has been speculated that malabsorption of L
      dopa from the small intestine occurs. It was reported that gastric retention in
      Parkinson's disease (PD) patients with motor fluctuations is increased as
      compared with that in PD without fluctuations. Because L-dopa therapy may worsen
      the symptoms of delayed gastric emptying (GE), it was not clear whether the
      delayed GE of PD patients with motor fluctuation was affected by L-dopa therapy.
      We assessed GE in PD patients with and without motor fluctuations. We
      investigated GE in 40 patients with PD under long-term L-dopa therapy, 20
      fluctuators with "delayed-on" and "noon" phenomena, 20 nonfluctuators, and 20
      healthy volunteers. GE was examined by the 13C-acetate breath test ((13)CABT)
      [the half emptying time (HET), the peak time of the (13)C-%-dose-excess curve
      (T(max))], with expirations collected for 4 h after a test meal and analyzed for
      (13)CO(2) using an infrared (IR) spectrophotometer. The T(max) of GE as assessed
      using the (13)C-ABT was significantly delayed in all PD patients as compared with
      controls (P = 0.002). The HET was significantly delayed in all PD patients as
      compared with controls (P < 0.001). The T(max) and HET were not significantly
      delayed in PD patients with motor fluctuations as compared with PD patients
      without motor fluctuations. These results demonstrated that GE is commonly
      delayed in PD patients with long-term L-dopa therapy. Delayed GE does not differ
      between PD patients with and without motor fluctuations. This finding
      demonstrated that the motor fluctuation in PD may not be influenced by GE.

PMID- 19575259
TI  - Neuregulin-1 genotypes and eye movements in schizophrenia.
AB  - Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the
      neurocognitive processes that may involve NRG-1 in schizophrenia are unknown.
      Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are
      promising endophenotypes, which may be associated with brain dysfunctions
      underlying the pathophysiology of schizophrenia. The aim of this study was to
      investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia
      patients and healthy controls. Patients (N = 113) and controls (N = 106) were
      genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a
      surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and
      SNP8NRG243177, which has recently been associated with individual differences in
      brain function. Subjects underwent infrared oculographic assessment of AS and
      SPEM. The study replicates previous findings of impaired AS and SPEM performance
      in schizophrenia patients (all P < 0.005; all d = 0.5-1.5). SNP8NRG243177 risk
      allele carriers had marginally increased variability of AS spatial error (P =
      0.050, d = 0.3), but there were no significant genotype effects on other eye
      movement variables and no significant diagnosis-by-genotype interactions.
      Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for
      SNP8NRG243177) had numerically worse performance than non-carriers on most AS and
      SPEM variables. The results do not suggest that NRG-1 genotype significantly
      affects AS and SPEM task performance. However, the power of the sample to
      identify small effects is limited and the possibility of a type II error must be
      kept in mind. Larger samples may be needed to reliably investigate such gene
      effects on oculomotor endophenotypes.

PMID- 19575261
TI  - A misleading sensory level.

PMID- 19575262
TI  - Homocysteine levels in patients with Behcet's disease and patients with recurrent
      aphthous stomatitis.
AB  - The mechanism for vascular involvement of Behcet disease (BD) includes arterial
      and venous thrombosis. Although the exact etiology of systemic vasculitis and
      thrombosis is still unknown, many hypotheses have been suggested. One of these
      hypotheses is that hyperhomocysteinemia causes vascular disease and thrombosis.
      The aim of this study was to compare the levels of homocysteine, vitamin B(12),
      and folic acid of BD patients with those of recurrent aphthous stomatitis (RAS)
      patients and healthy controls. Forty-five BD patients, 47 RAS patients, and 69
      healty control subjects were included in this study. Vitamin B(12), folic acid,
      and homocysteine levels of the patients and controls were measured, and
      statistical differences among the groups were determined. BD patients had mostly
      cutaneous symptoms. Arthritis and ocular and vascular involvement were seen in
      24.4%, 22%, and 11% of BD patients, respectively. No significant difference was
      detected among the groups in the levels of vitamin B(12), folic acid, and
      homocysteine. There was no significant difference in any parameters according to
      sex and age of the patients and activity of BD and if the patients with BD were
      treated or not. Homocysteine level inversely correlated with vitamin B(12) and
      folic acid levels in the BD group. We could not find any differences in
      homocysteine, vitamin B(12), and folic acid levels between BD and RAS patients
      and controls. This may be due to the fact that our patients mostly had cutaneous
      symptoms rather than vascular involvement.

PMID- 19575263
TI  - Atomic analysis and hardness measurement of the cavity prepared by laser.
AB  - The purpose of this study was to compare the compositional changes and
      microhardness of the cavity floor prepared by erbium, chromium:yttrium-scandium
      gallium-garnet (Er,Cr:YSGG) laser irradiation with those of the conventional bur
      prepared cavity. A total of 16 extracted human molar teeth (with no carious
      lesions or repairs) were selected for this study. On the buccal and lingual
      (palatal) surfaces of each tooth, cavities (diameter 3 mm, depth 2 mm) were
      prepared with an Er,Cr:YSGG laser system (Waterlase MD(TM), USA) and high-speed
      turbine. The cavities were cross-sectioned and subjected to atomic analysis by
      scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDX) and
      Vickers hardness test. Statistical analyses were performed with t-tests. Surface
      characteristics of the prepared cavities were also investigated by SEM. No
      significant differences were found between the calcium/phosphorus (Ca/P) ratio
      and Vickers hardness of laser- and bur-prepared cavities. The SEM observation
      revealed that the lased cavity surface was irregular, and there was also an
      absence of smear layer; the orifices of dentinal tubules were exposed.
      Microhardness measurement of the cavity floor confirmed that the Er,Cr:YSGG laser
      produced a clean-cut surface of the cavity.

PMID- 19575264
TI  - Distribution and possible function of the marine alkaloid, norzoanthamine, in the
      zoanthid Zoanthus sp. using MALDI imaging mass spectrometry.
AB  - The role of the marine alkaloid, norzoanthamine, in the colonial zoanthid
      Zoanthus sp. was previously unknown. High concentrations of norzoanthamine are
      present in the epidermal tissue of Zoanthus sp., as determined using protonated
      molecular ion peak mapping of norzoanthamine by matrix-assisted laser
      desorption/ionization mass spectrometry and high-performance liquid
      chromatography quantification. Sodium dodecylsulfate polyacrylamide gel
      electrophoresis experiments indicate that norzoanthamine increases the resistance
      of collagen to damage from UV light, probably not via UV light absorption, but by
      strengthening collagen itself, thus suggesting that collagen strengthening may be
      the function of norzoanthamine in Zoanthus sp.

PMID- 19575265
TI  - Chemotaxis disruption in Pratylenchus scribneri by tall fescue root extracts and
      alkaloids.
AB  - Tall fescue (Festuca arundinacea) forms a symbiotic relationship with the
      clavicipitalean fungal endophyte Neotyphodium coenophialum. Endophyte-infected
      grass is tolerant to nematode, but the factors responsible are unknown. One
      objective of this work was to determine if root extracts of tall fescue effected
      chemoreceptor activity of Pratylenchus scribneri by using an in vitro
      chemoreception bioassay. Another objective was to determine if specific ergot
      alkaloids (ergovaline, ergotamine, a-ergocryptine, ergonovine), and loline
      alkaloids, all produced by the fungal endophyte, altered chemotaxis with this
      bioassay. Methanolic extract from roots altered chemotaxis activities in this
      nematode but only from roots of plants cultured 45 > or = d, which repelled
      nematodes. Extracts prepared from noninfected grasses were attractants. This
      assay indicated that the alkaloids were either repellents or attractants. N
      formylloline was an attractant at concentrations of 20 microg/ml and lower, while
      at higher concentrations it was a repellent. Ergovaline, the major ergot alkaloid
      produced by the endophyte, was repellent at both high and low concentrations and
      caused complete death of the nematodes.

PMID- 19575266
TI  - Preoperative chemotherapy and potential impact on re-excision for early breast
      cancer.

PMID- 19575268
TI  - Adequacy of hospital discharge summaries in documenting tests with pending
      results and outpatient follow-up providers.
AB  - BACKGROUND: Poor communication of tests whose results are pending at hospital
      discharge can lead to medical errors. OBJECTIVE: To determine the adequacy with
      which hospital discharge summaries document tests with pending results and the
      appropriate follow-up providers. DESIGN: Retrospective study of a randomly
      selected sample PATIENTS: Six hundred ninety-six patients discharged from two
      large academic medical centers, who had test results identified as pending at
      discharge through queries of electronic medical records. INTERVENTION AND
      MEASUREMENTS: Each patient's discharge summary was reviewed to identify whether
      information about pending tests and follow-up providers was mentioned. Factors
      associated with documentation were explored using clustered multivariable
      regression models. MAIN RESULTS: Discharge summaries were available for 99.2% of
      668 patients whose data were analyzed. These summaries mentioned only 16% of
      tests with pending results (482 of 2,927). Even though all study patients had
      tests with pending results, only 25% of discharge summaries mentioned any pending
      tests, with 13% documenting all pending tests. The documentation rate for pending
      tests was not associated with level of experience of the provider preparing the
      summary, patient's age or race, length of hospitalization, or duration it took
      for results to return. Follow-up providers' information was documented in 67% of
      summaries. CONCLUSION: Discharge summaries are grossly inadequate at documenting
      both tests with pending results and the appropriate follow-up providers.

PMID- 19575269
TI  - Should guidelines incorporate evidence on patient preferences?

PMID- 19575270
TI  - The effect of patient race and blood pressure control on patient-physician
      communication.
AB  - BACKGROUND: Racial disparities in hypertension control contribute to higher rates
      of cardiovascular mortality among blacks. Patient-physician communication quality
      is associated with better health outcomes, including blood pressure (BP) control.
      Both race/ethnicity and BP control may adversely affect communication. OBJECTIVE:
      To determine whether being black and having poor BP control interact to adversely
      affect patient-physician communication more than either condition alone, a
      situation referred to as "double jeopardy." DESIGN, SETTINGS, AND PATIENTS: Cross
      sectional study of enrollment data from a randomized controlled trial of
      interventions to enhance patient adherence to therapy for hypertension.
      Participants included 226 hypertensive patients and 39 physicians from 15 primary
      care practices in Baltimore, MD. MEASUREMENTS: Communication behaviors and visit
      length from coding of audiotapes. RESULTS: After controlling for patient and
      physician characteristics, blacks with uncontrolled BP have shorter visits (B = 
      3.9 min, p < 0.01) with less biomedical (B = -24.0, p = 0.05), psychosocial (B = 
      19.4, p < 0.01), and rapport-building (B = -19.5, p = 0.01) statements than
      whites with controlled BP. Of all communication outcomes, blacks with
      uncontrolled BP are only in "double jeopardy" for a patient positive affect
      coders give them lower ratings than all other patients. Blacks with controlled BP
      also experience shorter visits and less communication with physicians than whites
      with controlled BP. There are no significant communication differences between
      the visits of whites with uncontrolled versus controlled BP. CONCLUSIONS: This
      study reveals that patient race is associated with the quality of patient
      physician communication to a greater extent than BP control. Interventions that
      improve patient-physician communication should be tested as a strategy to reduce
      racial disparities in hypertension care and outcomes.

PMID- 19575271
TI  - Herbal supplement use and blood lead levels of United States adults.
AB  - BACKGROUND: Some herbal supplements may contain lead. OBJECTIVE: To examine
      whether use of specific herbal dietary supplements during the last 30 days is
      associated with blood lead levels in US men and women. DESIGN: Cross-sectional
      analysis. STUDY POPULATION: NHANES participants from 1999-2004, a representative
      sample of the civilian non-institutionalized US population. MEASUREMENTS: Lead
      was measured in blood. Associations between lead and self-reported supplement use
      were estimated using multivariable regression weighted to account for NHANES
      sampling. Herbal supplements investigated were those previously reported to
      contain high heavy metal content: Ayurvedic or traditional Chinese medicine
      herbs, echinacea, ginkgo, ginseng, St. John's wort, and "other" herbs
      (specifically, kava, valerian, black cohosh, bee pollen, and nettle). MAIN
      RESULTS: Among 6,712 women > or =20 years, those using herbal supplements had
      lead levels that were 10% higher than non-users (95% CI 3%-17%, p = 0.005). Women
      using Ayurvedic or traditional Chinese medicine herbs, St. John's wort, and
      "other" herbs had lead levels 24% (95% CI 5%-45%, p = 0.01), 23% (95% CI 4%-46%),
      p = 0.02), and 21% (95% CI 2%-44%, p = 0.03) higher, respectively, than non
      users. No significant associations were observed between herb use and lead levels
      among men (n = 6,095). Among reproductive-aged women (16-45 years), herbal
      supplement users had lead levels 20% higher than non-users (95% CI 5%-34%, p =
      0.008). In contrast, garlic and other dietary supplements were not associated
      with higher lead levels. CONCLUSION: Use of specific herbal supplements is
      associated with higher blood lead levels among women. Our data suggest testing
      guidelines for herbal supplements and regulations limiting lead in supplements
      are needed.

PMID- 19575272
TI  - Improvement in glycemic control in morbidly obese type 2 diabetic subjects by
      gastric stimulation.
AB  - BACKGROUND: Gastric electrical stimulation synchronized to the refractory period
      of gastric electrical activity and applied during meals was evaluated for safety
      and for improvement of body weight and glycemic control in obese type 2 diabetes.
      METHODS: The study involved obese diabetic type 2 (ODM) patients in a multicenter
      open-label European feasibility trial. A total of 24 ODM (nine males, 15 females)
      treated with insulin and/or oral hyperglycemic agents and body mass index between
      33.3 to 49.7 kg/m(2) were implanted laparoscopically with a TANTALUS system.
      RESULTS: There were 18 adverse events related to the implant procedure or the
      device reported in 12 subjects. All were short lived and resolved with no
      sequelae. In the 21 subjects that reached the 1-year visit weight was reduced by
      4.5 +/- 2.7 kg (p < 0.05) and HbA1c by 0.5 +/- 0.3% (p < 0.05). In a subgroup (n
      = 11) on stable or reduced oral medication, weight was reduced by 6.3 +/- 3.4 kg
      (p < 0.05) and HbA1c by 0.9 +/- 0.4% (p < 0.05). The group on insulin (n = 6) had
      no significant changes in weight and HbA1c. CONCLUSIONS: The TANTALUS system is
      well tolerated in obese type 2 diabetic subjects. Gastric electrical stimulation
      can potentially improve glucose metabolism and induce weight loss in obese
      diabetic patients, who are not well controlled on oral antidiabetic therapy.
      Further evaluation is required to determine whether this effect is due to induced
      weight loss and/or to direct signal dependent mechanisms.

PMID- 19575273
TI  - T-tube gastrostomy as a novel approach for distal staple line disruption after
      sleeve gastrectomy for morbid obesity: case report and review of the literature.
AB  - Laparoscopic sleeve gastrectomy has recently become a feasible option in the
      management of morbid obesity. One of the most feared complications of this
      procedure is staple line disruption and leakage. There are, to our knowledge, few
      literature reports that try to explain the reasons and management of this rare
      but serious complication. We report a case of staple line disruption that was
      managed using a T-tube gastrostomy. A 50-year-old female, 2 weeks status post
      sleeve gastrectomy in an outside facility, was admitted to the emergency room at
      Cleveland Clinic Florida with new onset of fever, abdominal pain, jaundice,
      hematemesis, and melena. A computed tomography scan of the abdomen revealed a
      large extravasation of contrast material parallel to the gastric sleeve. A
      diagnostic laparoscopy was performed that showed a distal and proximal disruption
      of the staple line. A T-tube gastrostomy with a large proximal and distal limb
      was placed into the most distal area of disruption. After thorough over sewing
      and drainage of the proximal site and T-tube, a feeding jejunostomy was placed.
      The T-tube permitted to control the leak and to have a controlled fistula. Four
      weeks postoperatively, the T-tube was removed after the patient had a negative
      Gastrografin study and tolerated oral fluids with a clamped T-tube. The long-term
      recovery and follow-up were uneventful. T-tube gastrostomy appears to be a safe
      and feasible treatment option for staple line disruption after vertical sleeve
      gastrectomy. Early detection and drainage remain the most important principles to
      manage this type of complication.

PMID- 19575275
TI  - Replication and pathogenesis associated with H5N1, H5N2, and H5N3 low-pathogenic
      avian influenza virus infection in chickens and ducks.
AB  - A comparative study examining replication and disease pathogenesis associated
      with low-pathogenic H5N1, H5N2, or H5N3 avian influenza virus (AIV) infection of
      chickens and ducks was performed. The replication and pathogenesis of highly
      pathogenic AIV (HPAIV) has received substantial attention; however, the behavior
      of low-pathogenic AIVs, which serve as precursors to HPAIVs, has received less
      attention. Thus, chickens or ducks were inoculated with an isolate from a wild
      bird [A/Mute Swan/MI/451072/06 (H5N1)] or isolates from chickens
      [A/Ck/PA/13609/93 (H5N2), A/Ck/TX/167280-4/02 (H5N3)], and virus replication,
      induction of a serological response, and disease pathogenesis were investigated,
      and the hemagglutinin and neuraminidase (NA) gene sequences of the isolates were
      determined. Virus isolated from tracheal and cloacal swabs showed that H5N1
      replicated better in ducks, whereas H5N2 and H5N3 replicated better in chickens.
      Comparison of the NA gene sequences showed that chicken-adapted H5N2 and H5N3
      isolates both have a deletion of 20 amino acids in the NA stalk region, which was
      absent in the H5N1 isolate. Histopathological examination of numerous organs
      showed that H5N2 and H5N3 isolates caused lesions in chickens in a variety of
      organs, but to a greater extent in the respiratory and intestinal tracts, whereas
      H5N1 lesions in ducks were observed mainly in the respiratory tract. This study
      suggests that the H5N1, H5N2, and H5N3 infections occurred at distinct sites in
      chicken and ducks, and that comparative studies in different model species are
      needed to better understand the factors influencing the evolution of these
      viruses.

PMID- 19575274
TI  - Cerebellar brain-derived neurotrophic factor, nerve growth factor, and
      neurotrophin-3 expression in male and female rats is differentially affected by
      hypergravity exposure during discrete developmental periods.
AB  - We previously reported that the effects of perinatal exposure to hypergravity on
      cerebellum and motor functions in rat neonates are strongly dependent on the
      specific developmental period of exposure. In the present study, we explored the
      hypothesis that neurodevelopmental changes are associated with altered expression
      of brain neurotrophins critical for normal brain growth and differentiation. We
      compared the effects of hypergravity exposure during four developmental periods:
      period I extended from gestational day (G) 8 through G15; period II from G15 to
      birth, period III from birth to postnatal day (P) 6; and period IV extended from
      G8-P12. For comparison we used stationary control (SC) neonates not exposed to
      hypergravity. Neurotrophins, brain-derived neurotrophic factor (BDNF), nerve
      growth factor (NGF), and neurotrophin 3 (NT-3) levels were measured in cerebellar
      homogenates prepared from postnatal day 12 male and female rat neonates using
      specific ELISAs. Hypergravity exposure affected individual neurotrophins
      differently and the effect was further determined by the period of hypergravity
      exposure. ANOVA showed: (1) a significant effect of the period of exposure to
      hypergravity on cerebellar BDNF (p = 0.009), with maximal decrease of 28.7% in
      males and 32.1% in females following exposure during period III; (2) a
      significant effect on NGF (p < 0.0001), with maximal decrease of 35.6% in male
      and 48.8% in female neonates following exposure during period III; (3) no
      statistically significant effect on NT-3 expression with a trend towards
      decreased expression in female rats following exposure during period IV. Although
      the molecular mechanisms underlying the differential neurotrophins' response to
      hypergravity are not clear, an altered pattern of their expression is likely to
      contribute to neurodevelopmental changes and impaired sensorimotor behavior in
      exposed neonates.

PMID- 19575276
TI  - The complete nucleotide sequence and genome organization of tomato infectious
      chlorosis virus: a distinct crinivirus most closely related to lettuce infectious
      yellows virus.
AB  - The complete nucleotide sequence of tomato infectious chlorosis virus (TICV) was
      determined and compared with those of other members of the genus Crinivirus. RNA
      1 is 8,271 nucleotides long with three open reading frames and encodes proteins
      involved in replication. RNA 2 is 7,913 nucleotides long and encodes eight
      proteins common within the genus Crinivirus that are involved in genome
      protection, movement and other functions yet to be identified. Similarity between
      TICV and other criniviruses varies throughout the genome but TICV is related more
      closely to lettuce infectious yellows virus than to any other crinivirus, thus
      identifying a third group within the genus.

PMID- 19575277
TI  - Interaction of tomato yellow leaf curl virus with diverse betasatellites enhances
      symptom severity.
AB  - The complete nucleotide sequence was determined for a begomovirus isolated from
      tomato exhibiting leaf curling and yellowing symptoms in Tochigi Prefecture in
      Japan. The genome organization of this virus was similar to those of other Old
      World monopartite begomoviruses. Neither a DNA betasatellite nor a DNA-B
      component was detected. It had the highest total nucleotide sequence identity
      (99%) with tomato yellow leaf curl virus-Israel[Japan:Tosa:2005] (TYLCV
      IL[JR:Tos:05]) and TYLCV-Israel[Japan:Haruno:2005] (TYLCV-IL[JR:Han:05]). Its
      coat protein V1 also showed an identical amino acid sequence with those of TYLCV
      IL[JR:Tos:05] and TYLCV-IL[JR:Han:05]. Thus, the begomovirus was determined to be
      an isolate of TYLCV-IL designated as TYLCV-Israel[Japan:Tochigi:2007] (TYLCV
      IL[JR:Toc:07]). We investigated the interaction of TYLCV-IL[JR:Toc:07] with two
      known satellites associated with tomato yellow dwarf disease in Japan, tobacco
      leaf curl Japan betasatellite [Japan:Ibaraki:2006] and honeysuckle yellow vein
      mosaic betasatellite [Japan:Nara:2006], as well as with tomato leaf curl
      Philippines betasatellite [Philippines:Laguna1:2008], in tomato and Nicotiana
      benthamiana plants. TYLCV-IL[JR:Toc:07] trans-replicated these betasatellites,
      inducing more severe tomato yellow leaf curl disease-related symptoms than TYLCV
      IL[JR:Toc:07] alone.

PMID- 19575278
TI  - Molecular characterization of a closterovirus from carrot and its identification
      as a German isolate of Carrot yellow leaf virus.
AB  - A high-molecular-weight dsRNA (approximately 15 kbp) was isolated from chlorotic
      leaves of a carrot plant and used for determining the entire nucleotide sequence
      of a closterovirus. The complete genome of this carrot closterovirus (CCV) was
      16.4 kb in length and contained ten open reading frames (ORFs). The genome
      organization of CCV resembled that of beet yellow stunt virus, but ORF2 and ORF3
      were in a reversed order. Based on Hsp70h sequences, CCV is most closely related
      to carnation necrotic fleck virus and mint virus 1, two viruses of the genus
      Closterovirus (family Closteroviridae). The major coat protein gene of CCV was
      expressed in Escherichia coli for raising an antiserum. This permitted routine
      detection of CYLV by DAS-ELISA and immunoelectron microscopy and was used for
      demonstrating the bipolar nature of the CCV virion. Moreover, the antiserum gave
      a Western blot reaction with a reference sample of a Carrot yellow leaf virus
      (CYLV) isolate from the Netherlands, suggesting that CCV is a German isolate of
      CYLV.

PMID- 19575279
TI  - Label-free quantitation, an extension to 2DB.
AB  - Determining the differential expression of proteins under different conditions is
      of major importance in proteomics. Since mass spectrometry-based proteomics is
      often used to quantify proteins, several labelling strategies have been
      developed. While these are generally more precise than label-free quantitation
      approaches, they imply specifically designed experiments which also require
      knowledge about peptides that are expected to be measured and need to be
      modified. We recently designed the 2DB database which aids storage, analysis, and
      publication of data from mass spectrometric experiments to identify proteins.
      This database can aid identifying peptides which can be used for quantitation.
      Here an extension to the database application, named MSMAG, is presented which
      allows for more detailed analysis of the distribution of peptides and their
      associated proteins over the fractions of an experiment. Furthermore, given
      several biological samples in the database, label-free quantitation can be
      performed. Thus, interesting proteins, which may warrant further investigation,
      can be identified en passant while performing high-throughput proteomics studies.

PMID- 19575280
TI  - Service satisfaction on discharge from a psychiatric mother and baby unit: a
      representative patient survey.
AB  - In this representative survey of 57 women before discharge from a psychiatric
      mother and baby unit satisfaction levels were high for most aspects of the
      service. However, the qualitative part of the study highlighted issues that were
      not captured by completion of the satisfaction questionnaire. These included a
      need for greater support from nursing staff and a high level of distress about
      interactions with children's social workers in some patients. The latter aspect
      requires further exploration. For future surveys we recommend to use quantitative
      as well as qualitative methodology.

PMID- 19575281
TI  - Diagnostic performance of Tc-99m HMPAO SPECT for early and late onset Alzheimer's
      disease: a clinical evaluation of linearization correction.
AB  - OBJECTIVE: This study examined the influence of linearization correction (LC) on
      brain perfusion single-photon emission computed tomography (SPECT) for the
      diagnosis of Alzheimer's disease (AD). METHODS: The early onset group (<65 years
      old) consisted of 10 patients with AD, and the late onset group (>/=65 years old)
      of 13 patients with AD. Age-matched controls included seven younger and seven
      older normal volunteers. Tc-99m hexamethyl propyleneamine oxine (HMPAO) SPECT
      images were reconstructed with or without LC [LC (+) or LC (-)] and a statistical
      analysis was performed using a three-dimensional stereotactic surface projection
      (3D-SSP). In addition, a fully automatic diagnostic system was developed, which
      calculated the proportion of the number of abnormal pixels in the superior and
      inferior parietal lobule, as well as in the precuneus and posterior cingulate
      gyrus. RESULTS: The areas under the receiver-operating characteristic curve
      (AUCs) of the early onset group for conventional axial SPECT images, SPECT + 3D
      SSP images and the fully automatic diagnostic system were 0.71, 0.88, and 0.92 in
      LC (-) and 0.67, 0.85, and 0.91 in LC (+), respectively. The AUCs of the late
      onset group were 0.50, 0.61, and 0.79 in LC (-) and 0.49, 0.67, and 0.85 in LC
      (+), respectively. CONCLUSION: LC on Tc-99m HMPAO SPECT did not significantly
      influence the diagnostic performance for differentiating between AD and normal
      controls in either early or late onset AD. Further examination with individuals
      suffering from very mild dementia is, therefore, expected to elucidate the effect
      of LC on minimally hypoperfused areas.

PMID- 19575282
TI  - High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide
      (USPIO) in the evaluation of axillary lymph nodes in patients with early stage
      breast cancer: preliminary results.
AB  - BACKGROUND: The purpose of this study was to examine the utility of high
      resolution magnetic resonance (MR) lymphography using ultrasmall
      superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in
      patients with early stage breast cancer. METHODS: Ten women with breast cancer
      without swollen axillary lymph nodes were enrolled in this study. High-resolution
      MR lymphography was performed 24 h after administration of USPIO. On the MR
      examination, a 3-inch surface coil was placed on the sentinel lymph node (SLN)
      parts as defined by a radioisotope (RI) scintigraphy method, and T2*-weighted
      (T2*W) and T1-weighted (T1W) images were obtained. Detected nodes were
      differentiated as normal or diseased nodes by the enhancement patterns. The day
      after MR examination, SLN biopsy (SNB) was performed. The imaging results were
      compared to the histopathologic findings. RESULTS: On MR images, the mean number
      of detectable nodes was 7.9 per patient. Eight patients who histopathologically
      had no metastatic lymph nodes were diagnosed as nonmetastatic and two patients
      who had 3- and 6-mm metastatic areas in the node, respectively, were diagnosed as
      metastatic preoperatively. No side effects were noted. CONCLUSIONS: High
      resolution MR lymphography using USPIO enabled us to obtain good axillary lymph
      node evaluation results. These results suggest that this method of imaging may
      contribute to better preoperative lymph node staging.

PMID- 19575283
TI  - Ultrasound findings and histological features of ductal carcinoma in situ
      detected by ultrasound examination alone.
AB  - BACKGROUND: With the increasing use of high-resolution ultrasound (US)
      examination, many breast carcinomas that cannot be identified by mammography
      (MMG) alone have been detected. Many of these carcinomas are ductal carcinoma in
      situ (DCIS) and small-sized invasive carcinomas. Until date, DCISs have often
      been described as palpable masses with calcifications on MMG, but what are the
      characteristics of DCISs that are detectable by US alone? METHODS: One hundred
      fifty cases with DCIS that we experienced at our clinic from 2003 to 2007 were
      classified into 47 cases (echo group) diagnosed by US alone and 103 cases (MMG/PE
      group) diagnosed by MMG or clinically. RESULTS: US findings of the echo group
      showed cystic or solid lesions in 37 cases (79%). The mean age of the echo group
      was significantly higher than that of the MMG/PE group (59.6 vs. 51.2 years; P <
      0.01). Tumor sizes detected by US were 5.7 + 2.8 and 11.5 + 10.8 mm (P < 0.001),
      respectively. The tumor sizes of the echo group were, therefore, approximately
      half that of the MMG/PE group. Extensive intraductal components were
      significantly fewer in the echo group, and tumor grades of the echo group were
      significantly low (Van Nuys classification). In the echo group, all cases with a
      tumor size < 5 mm were grade 1 by Van Nuys classification. In addition, cases
      with > or = 5 mm tumor size had a significantly lower tumor grade in the echo
      group than in the MMG/PE group. CONCLUSIONS: Cystic or solid lesions accounted
      for approximately 80% of US findings of DCISs detected by US alone, and most were
      similar to benign forms. Moreover, most DCISs detected by US alone were localized
      and of low grade (Van Nuys classification).

PMID- 19575286
TI  - Anti-cancer, anti-diabetic and other pharmacologic and biological activities of
      penta-galloyl-glucose.
AB  - 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) is a polyphenolic compound
      highly enriched in a number of medicinal herbals. Several in vitro and a handful
      of in vivo studies have shown that PGG exhibits multiple biological activities
      which implicate a great potential for PGG in the therapy and prevention of
      several major diseases including cancer and diabetes. Chemically and
      functionally, PGG appears to be distinct from its constituent gallic acid or tea
      polyphenols. For anti-cancer activity, three published in vivo preclinical cancer
      model studies with PGG support promising efficacy to selectively inhibit
      malignancy without host toxicity. Potential mechanisms include anti-angiogenesis;
      anti-proliferative actions through inhibition of DNA replicative synthesis, S
      phase arrest, and G(1) arrest; induction of apoptosis; anti-inflammation; and
      anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2, VEGFR1, AP
      1, SP-1, Nrf-2, and MMP-9. For anti-diabetic activity, PGG and analogues appear
      to improve glucose uptake. However, very little is known about the absorption,
      pharmacokinetics, and metabolism of PGG, or its toxicity profile. The lack of a
      large quantity of highly pure PGG has been a bottleneck limiting in vivo
      validation of cancer preventive and therapeutic efficacies in clinically relevant
      models.

PMID- 19575284
TI  - Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy
      compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive
      breast cancer in Japan.
AB  - BACKGROUND: To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF)
      chemotherapy and the anthracycline-containing regimen cyclophosphamide,
      epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the
      latter. METHODS: A total of 294 patients with axillary node-positive primary
      breast cancer of STAGE I-IIIa were randomly assigned to either CEF
      [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60
      mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or
      CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1
      and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were
      comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was
      concomitantly given to estrogen receptor (ER)-positive patients and those with
      undetermined ER status for 2 years. RESULTS: The overall 5-year survival was
      77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)],
      and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p =
      0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not
      show a significant difference, both overall and disease-free survivals were
      higher for CEF according to the point estimates. Adverse drug reactions (ADRs)
      occurred more frequently in CEF. CONCLUSION: Whereas CEF had a good trend compare
      with CMF, it could not be proven statistically significant. The principal cause
      of the failure seems to be insufficient power, that is, the dose intensity (EPI:
      60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of
      trial subjects was small because of the background of the times, which made the
      accumulation of cases extremely difficult. However, the trial should be
      considered to be meaningful, as it was the first, formally conducted controlled
      trial on chemotherapy in Japan.

PMID- 19575288
TI  - Retraction note. An experimental study of the neurogenic and the immunological
      contribution to "tennis elbow" in rats.

PMID- 19575287
TI  - Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA
      mutations.
AB  - BACKGROUND: Hyper-immunoglobulin M (HIGM) syndromes are a heterogeneous group of
      primary immunodeficiency disorders, characterized by recurrent infections
      associated with decreased serum levels of immunoglobulin G (IgG) and IgA and
      normal to increased serum levels of IgM. These patients have immunoglobulin class
      switch recombination defects, caused by mutations in several genes. METHODS: In
      order to investigate clinical and immunological manifestations of HIGM in Iran,
      23 Iranian patients with an age range of 5 months to 35 years, who were followed
      up over a period of 17 years, were studied. Fourteen of the 23 patients were
      screened for CD40L, AICDA, UNG, and CD40 gene mutations, using polymerase chain
      reaction followed by direct sequencing. RESULTS: All patients, except one,
      initially presented with infectious diseases; the most common manifestations were
      respiratory tract infections. Six different CD40L mutations were identified, five
      were novel, one splicing (IVS1+2T>C), three missense (T254M, G167R, L161P), and
      two frame shift deletions (T29fsX36 and D62fsX79). In addition, one novel AICDA
      mutation (E122X) was detected. No mutation was found in six out of 14 analyzed
      patients. CONCLUSION: CD40L mutations comprise the most common type of
      immunoglobulin class switch recombination defects. There are several patients
      with HIGM phenotype, in which the underlying genetic defects remain to be
      identified. Other defects such as those in components of the mismatch repair
      mechanism could be potential candidates for the latter.

PMID- 19575289
TI  - Suppression of collagen production in norepinephrine stimulated cardiac
      fibroblasts culture: differential effect of alpha and beta-adrenoreceptor
      antagonism.
AB  - OBJECTIVES: Prolonged sympathetic activation is damaging to the heart and
      experimental norepinephrine (NE) infusion induces the deposition of myocardial
      collagen. This study investigated the effects of NE on collagen and transforming
      growth factor-beta1 (TGF-beta1) gene expression in rat cardiac fibroblasts (CF)
      culture, and compared the anti-fibrotic effect of alpha and beta (both selective
      and non-selective adrenergic receptor antagonists) receptors. METHODS AND
      RESULTS: Rat CF were cultured in the presence of NE (0.01 to 100 muM) for 24
      hours. Procollagen types I and III as well as TGF-beta1 gene expressions were
      measured by real-time quantitative PCR method. Collagen protein level was
      measured by Sirius red-based colorimetric method and Western blot analysis. The
      optimal dose of NE on fibrogenesis was 0.1 muM. Incubation for 24 hours increased
      procollagen I, III and TGF-beta1 gene expression by 1.35 +/- 0.23, 1.26 +/- 0.16
      and 1.35 +/- 0.21 fold, respectively (all p < 0.05). The collagen protein was
      increased by both Sirius-red assay (0.120 +/- 0.03 vs 0.093 +/- 0.04 microg/total
      microg of protein, p < 0.05) and Western blot analysis (1.29 +/- 0.26 fold, p <
      0.05), when compared with the control group. Addition of carvedilol (a non
      selective beta-blocker with alpha-blockage activity) inhibited the effect of NE
      on procollagen I (0.64 +/- 0.17 vs 1.28 +/- 0.08 fold, p < 0.01), procollagen III
      gene (0.47 +/- 0.16 vs 1.45 +/- 0.29 fold, p < 0.01) and collagen protein
      expressions (0.99 +/- 0.12 vs 1.26 +/- 0.31 fold, p < 0.05, respectively).
      Doxazosin (an alpha-blocker) also inhibited the effect of NE on procollagen I
      (0.88 +/- 0.30 vs 1.28 +/- 0.08 fold, p < 0.01), procollagen III gene (0.64 +/-
      0.13 vs 1.45 +/- 0.29 fold, p < 0.01) and collagen protein expression (0.90 +/-
      0.11 vs 1.26 +/- 0.31 fold, p < 0.01 respectively). Such inhibitory effects were
      not seen in metoprolol (a beta1-selective blocker) and propranolol (a non
      selective beta blocker). Furthermore, all the 4 drugs were unable to inhibit the
      NE induced TGF-beta1 gene over-expression. CONCLUSIONS: In conclusion, NE
      increased collagen gene and protein expressions in CF culture. This effect is
      likely mediated through alpha-receptor as they were normalized by pretreatment
      with carvedilol and doxazosin, but not beta-blockers such as propranolol and
      metoprolol. Also, TGF-beta1 doesn't seem to play a role in carvedilol inhibition
      of NE induced fibrogenesis.

PMID- 19575291
TI  - Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer
      patients: the impact of addition of taxanes to anthracycline-based regimens.
AB  - Adjuvant chemotherapy prolongs survival in patients with breast cancer, but it
      also causes side effects such as ovarian-function suppression. The incidence of
      chemotherapy-induced amenorrhea (CIA) varies depending on the patients' age, dose
      and the type of chemotherapy that they receive. CIA produced by anthracycline
      based regimens has been widely studied, but less is known about the incidence of
      CIA caused by the combined use of taxanes and anthracyclines. It has been
      suggested that tamoxifen might influence the maintenance of amenorrhea. However,
      most studies of CIA have explored series of patients with hormone-sensitive and
      hormone-resistant tumors, so data about CIA could be strongly influenced by
      endocrine adjuvant therapy. The aims of our study were to assess the incidence of
      CIA with the addition of taxanes to anthracyclines regimens in pre- or
      perimenopausal patients diagnosed with hormone-sensitive breast cancer and to
      determine predictive factors for CIA. A retrospective non-randomized study was
      conducted in the Hospital Clinico Universitario of Valencia, Spain. Three hundred
      and five premenopausal and perimenopausal patients were recruited between January
      1998 and May 2005, 212 of whom had been treated with anthracycline-based regimens
      and 93 with a combination of anthracyclines and taxanes. Amenorrhea was permanent
      in 222 patients (93.7%) and menses returned in 6.3%. CIA was present in 75.5% of
      patients treated with anthracyclines and in 82.7% of patients treated with
      anthracyclines and taxanes. This difference did not reach statistical
      significance (p = 0.16). CIA appeared in 95% of patients older than 45 years,
      while the proportion of CIA decreased to 52% in patients younger than 40 years.
      This suggests age as an important predictive factor for CIA (p < 0.001). Although
      a slightly superior incidence of CIA in patients with hormone-sensitive tumors
      treated with combination regimens was observed, no statistically significant
      difference in incidence was found. Age was found to be the main predictive factor
      for CIA in both groups.

PMID- 19575290
TI  - Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal
      cancer syndrome.
AB  - Whether or not breast cancer can be a feature of the hereditary nonpolyposis
      colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if
      defective mismatch repair (MMR) may indeed play a role in breast cancer, we used
      the Danish HNPCC register to identify all breast cancers that occurred in MMR
      gene mutation carriers. In total, 20 female mutation carriers were diagnosed with
      breast cancer at mean 50 years of age. These tumors were predominantly ductal
      carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR
      protein immunostaining showed loss of expression of MLH1, MSH2 or MSH6
      corresponding to the mutations identified in 7 of the 16 cases investigated, and
      these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of
      defective MMR in a substantial proportion of the breast cancers studied links yet
      another tumor type to HNPCC. Though the low number do not motivate surveillance,
      our observation supports a role for defective MMR in breast cancer progression in
      HNPCC, presumably through accelerated accumulation of mutations in breast cancer
      associated genes.

PMID- 19575292
TI  - Pseudomyxoma peritonei masquerading as ascites secondary to alcoholic cirrhosis.

PMID- 19575293
TI  - Liver abscesses, pylephlebitis, and appendicitis in an adolescent male.

PMID- 19575294
TI  - Crohn's colitis complicated by cytomegalovirus infection.

PMID- 19575295
TI  - DNA damage- and stress-induced apoptosis occurs independently of PIDD.
AB  - The p53-induced protein with a death domain, PIDD, was identified as a p53 target
      gene whose main role is to execute apoptosis in a p53-dependent manner. To
      investigate the physiological role of PIDD in apoptosis, we generated PIDD
      deficient mice. Here, we report that, although PIDD expression is inducible upon
      DNA damage, PIDD-deficient mice undergo apoptosis normally not only in response
      to DNA damage, but also in response to various p53-independent stress signals and
      to death receptor (DR) engagement. This indicates that PIDD is not required for
      DNA damage-, stress-, and DR-induced apoptosis. Also, in the absence of PIDD,
      both caspase-2 processing and activation occur in response to DNA damage. Our
      findings demonstrate that PIDD does not play an essential role for all p53
      mediated or p53-independent apoptotic pathways.

PMID- 19575296
TI  - Memory-prediction errors and their consequences in schizophrenia.
AB  - Cognitive deficits play a central role in the onset of schizophrenia. Cognitive
      impairment precedes the onset of psychosis in at least a subgroup of patients,
      and accounts for considerable dysfunction. Yet cognitive deficits as currently
      measured are not significantly related to hallucinations and delusions. Part of
      this counterintuitive absence of a relationship may be caused by the lack of an
      organizing principle of cognitive impairment in schizophrenia research. We review
      literature suggesting that a system of memory-based prediction is central to
      human perception, thought and action , and forward the notion that many of the
      symptoms of schizophrenia are a result of a failure of this system.

PMID- 19575298
TI  - CheckShift improved: fast chemical shift reference correction with high accuracy.
AB  - The construction of a consistent protein chemical shift database is an important
      step toward making more extensive use of this data in structural studies.
      Unfortunately, progress in this direction has been hampered by the quality of the
      available data, particularly with respect to chemical shift referencing, which is
      often either inaccurate or inconsistently annotated. Preprocessing of the data is
      therefore required to detect and correct referencing errors. In an earlier study
      we developed CheckShift, a program for performing this task automatically. Now we
      spent substantial effort in improving the running time of the CheckShift
      algorithm, which resulted in an running time decrease of 90%, thereby achieving
      equivalent quality to the former version of CheckShift. The reason for the
      running time decrease is twofold. Firstly we improved the search for the optimal
      re-referencing offset considerably. Secondly, as CheckShift is based on a
      secondary structure prediction from the amino acid sequence (formally PsiPred was
      used), we evaluated a wide range of available secondary structure prediction
      programs focusing on the special needs of the CheckShift algorithm. The results
      of this evaluation prove empirically that we can use faster secondary structure
      prediction programs than PsiPred without sacrificing CheckShift's accuracy. Very
      recently Wang and Markley (2009) gave a small list of extreme outliers of the
      former version of the CheckShift web-server. Those were due to the empirical
      reduction of the search space implemented in the old version. The new version of
      CheckShift now gives very similar results to RefDB and LACS for all outliers
      mentioned in Table 1 of Wang and Markley (2009).

PMID- 19575299
TI  - Low-dose ethanol suppresses 17beta-estradiol activity in GH4C1 pituitary tumor
      cells.
AB  - The interaction of chronic alcohol consumption with estrogen has been recognized
      in various tissues; however, the potential mechanism has not been clearly
      defined. In this study, we made the following observations: (a) 0.01% (v/v)
      ethanol (corresponding to 1.7 mM) significantly elevated estrogen receptor alpha
      (ERalpha) protein content, stimulated activator protein-1 (AP-1)-dependent
      ERalpha transcriptional activities, and ultimately enhanced GH4C1 cells growth in
      vitro and (b) the same concentration of ethanol suppressed the stimulatory
      effects of 17beta-estradiol (E2; 10 nM) on both cell growth and cellular PRL
      accumulate through attenuation of ERalpha actions at both the estrogen response
      element and the AP-1 site. These observations raise the question as to what
      extent ethanol influences signal transduction pathways controlled by E2 in
      experimental medicine and biology.

PMID- 19575297
TI  - Cross-language differential item functioning of the job content questionnaire
      among European countries: the JACE study.
AB  - BACKGROUND: Little is known about cross-language measurement equivalence of the
      job content questionnaire (JCQ) PURPOSE: The purposes of this study were to
      assess the extent of cross-language differential item functioning (DIF) of the 27
      JCQ items in six languages (French, Dutch, Belgian-French, Belgian-Dutch
      (Flemish), Italian, and Swedish) from six European research centers and to test
      whether its effects on the scale-level mean comparisons among the centers were
      substantial or not. METHOD: A partial gamma coefficient method was used for
      statistical DIF analyses where the Flemish JCQ was the reference for other
      language versions. Additionally, equivalence between the Flemish and Dutch
      translations was subjected to a judgmental review. RESULTS: On average, 36% to
      39% of the total tested items appeared to be cross-language DIF items in the
      statistical analyses. The judgmental review indicated that half of the DIF items
      may be associated with translation difference. The impacts of the DIF items on
      the mean comparisons of the JCQ scales between the centers were non-trivial:
      underestimated skill discretion (Milan), underestimated decision authority
      (Leiden), underestimated psychological demands (Milan women), and incomparable
      coworker support (Gothenburg 95). CONCLUSION: Cross-language DIF of the JCQ among
      European countries should be considered in international comparative studies on
      psychosocial job hazards using JCQ scales.

PMID- 19575301
TI  - Cytogenetic anchoring of radiation hybrid and virtual maps of sheep chromosome X
      and comparison of X chromosomes in sheep, cattle, and human.
AB  - A comprehensive physical map was generated for Ovis aries chromosome X (OARX)
      based on a cytogenomics approach. DNA probes were prepared from bacterial
      artificial chromosome (BAC) clones from the CHORI-243 sheep library and were
      assigned to G-banded metaphase spreads via fluorescence in-situ hybridization
      (FISH). A total of 22 BACs gave a single hybridization signal to the X chromosome
      and were assigned out of 32 tested. The positioned BACs contained 16 genes and a
      microsatellite marker which represent new cytogenetically mapped loci in the
      sheep genome. The gene and microsatellite loci serve to anchor between the
      existing radiation hybrid (RH) and virtual sheep genome (VSG) maps to the
      cytogenetic OARX map, whilst the BACs themselves also serve as anchors between
      the VSG and the cytogenetic maps. An additional 17 links between the RH and
      cytogenetic maps are provided by BAC end sequence (BES) derived markers that have
      also been positioned on the RH map. Comparison of the map orders for the
      cytogenetic, RH, and virtual maps reveals that the orders for the cytogenetic and
      RH maps are most similar, with only one locus, represented by BAC CH243-330E18,
      mapping to relatively different positions. Several discrepancies, including an
      inverted segment are found when comparing both the cytogenetic and RH maps with
      the virtual map. These discrepancies highlight the value of using physical
      mapping methods to inform the process of future in silico map construction. A
      detailed comparative analysis of sheep, human, and cattle mapping data allowed
      the construction of a comparative map that confirms and expands the knowledge
      about evolutionary conservation and break points between the X chromosomes of the
      three mammalian species.

PMID- 19575302
TI  - The use of contrast-enhanced ultrasound with a second generation contrast medium:
      preliminary report in the dog.

PMID- 19575303
TI  - Proteomic study of antibiotic resistance in Escherichia coli strains.

PMID- 19575304
TI  - Freezing of canine semen in an animal-free protein extender.

PMID- 19575305
TI  - Echinococcosis: costs, losses and social consequences of a neglected zoonosis.
AB  - The socio-economic impact of echinococcosis, with special reference to cystic
      echinococcosis (CE) caused by Echinococcus granulosus, is reviewed. The following
      items are discussed: socio-economic consequences in humans; economic consequences
      in livestock; costs and benefits of control programmes; economic evaluation of
      control programmes; social reasons favouring the life cycle of CE; social,
      political and economic situations hindering the control of echinococcosis. Many
      consequences are difficult to evaluate from an economic point of view. However,
      many evaluations have shown that CE is an important (often neglected) public
      health and economic problem, especially in endemic areas, and that the socio
      economic evaluation of its consequences and of control actions proves
      indispensable to best use available resources and possibly tailor control
      strategies.

PMID- 19575306
TI  - Participatory appraisal of foot and mouth disease in the Afar pastoral area,
      northeast Ethiopia: implications for understanding disease ecology and control
      strategy.
AB  - Foot and mouth disease (FMD) is the most economically important disease of
      livestock that still affects extensive areas of the world. This study described
      the use of participatory appraisal tools such as pair-wise ranking, matrix
      scoring and proportional piling to assess the perception of livestock keepers
      about the clinical signs and epidemiological features of cattle diseases with
      particular emphasis on FMD. Strong agreement among informant groups (W = 0.710; P
      = 0.000) in pair wise ranking indicated that the diseases were common problem to
      all the selected districts. Matrix scoring of disease indicators/signs also
      showed strong agreement (W = 0.504 to 0.955; P = 0.000) that implied significant
      current veterinary knowledge by Afar pastoralists. Age specific means of annual
      incidence rates estimated by proportional piling were significantly (P < 0.05)
      different but negatively correlated for FMD, CBPP and pasteurellosis. However,
      correlation was not significant for anthrax, blackleg and other important
      diseases. Age specific means of annual mortality was significantly (P < 0.05) but
      negatively correlated for FMD, CBPP, pasteurellosis and other important cattle
      diseases with correlation coefficients of -0.72, -0.81, -0.8 and -0.55,
      respectively. However, correlation (r = 0.12) was not significant for anthrax and
      not correlated at all for blackleg. This study indicated that pastoralists have
      detailed knowledge about their livestock health problems, and hence the combined
      use of participatory appraisal and conventional methods is essential for an
      ultimate disease control strategy.

PMID- 19575308
TI  - Patient self-reporting of potential adverse drug reactions to non-steroidal anti
      inflammatory drugs in Thailand.
AB  - OBJECTIVES: To validate and pilot in Thailand a questionnaire to enable patients
      to identify and report symptoms perceived as potential ADRs from NSAIDs. To
      determine the questionnaire's usefulness in enabling Thai out-patients to report
      potential ADRs. To determine the frequency with which symptoms patients reported
      were recorded by health professionals and the frequency of ADRs to these drugs
      reported to the APRM Centre. To assess whether patients reported symptoms from
      non COX-selective inhibitors and COX-2 selective NSAIDs with different
      frequencies. SETTING: Out-patient departments (OPD) of a University teaching
      hospital in North-East Thailand. METHOD: A questionnaire which incorporated an
      extensive symptoms checklist, developed and validated in English, was translated,
      piloted and validated in Thai. This was distributed to patients receiving one of
      five NSAIDs. Causality assessment of the symptoms reported was undertaken by a
      pharmacist, using data on concomitant medicines and disease states from OPD
      records. OUTCOME MEASURES: Frequency and type of symptoms reported by patients,
      recording of these in OPD records, reports sent to APRM Centre. RESULTS: Piloting
      found that patients were able to understand the questionnaire, but were unaware
      of drug names. A response rate of 42% was obtained: 694 usable questionnaires
      were returned out of 1,654 distributed. Overall 73% of respondents reported at
      least one symptom perceived to be an ADR. Sixty percent of symptoms reported were
      classed as probably or possibly an ADR. Fewer symptoms per patient were reported
      by those taking COX-2 selective inhibitors (3.5) than those taking non-selective
      NSAIDs (5.5), although there were no differences in the frequency of GI symptoms
      reported between these two sub-classes, which may relate to other factors, such
      as age, previous GI problems and prescription of protective ulcer-healing
      therapy. Only 5% of symptoms were recorded in OPD records and reporting of ADRs
      to these drugs to the APRM Centre of the Thai FDA during the study was very
      limited. CONCLUSION: Thai out-patients were willing and able to complete
      questionnaires regarding potential ADRs. The questionnaire could form part of
      routine out-patient monitoring, aiding identification of ADRs, and may help to
      increase ADR reporting in Thailand.

PMID- 19575309
TI  - Association study of four variants in KCNQ1 with type 2 diabetes mellitus and
      premature coronary artery disease in a Chinese population.
AB  - Four single nucleotide polymorphisms (SNPs, rs2237892, rs2237895, rs2237897,
      rs2283228) in KCNQ1 are associated with type 2 diabetes mellitus in different
      ancestral groups. We investigated whether these 4 genetic markers are
      determinants of type 2 diabetes and premature coronary artery disease (CAD) in a
      Chinese population. We studied 398 consecutive patients, including 180 with
      coronary stenosis >or=50% or previous myocardial infarction (male <55 years,
      female <65 years) and 218 controls without documented CAD. CAD cases and controls
      were genotyped for 4 SNPs by using the ligase detection reaction method. The 3
      genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3
      genotypes CC, CT, TT were present in rs2237897 and rs2237892. No differences were
      found in genotype distribution and allele frequencies of these 4 SNPs between
      subjects with and without type 2 diabetes. Logistic regression showed that the
      risk of premature CAD in subjects carrying the CC genotype at rs2237892 was
      reduced by 90% in relation to individuals carrying the TT genotype (OR = 0.100,
      95% CI: 0.018-0.564, P = 0.009). The association of other 3 SNPs with premature
      CAD could not be detected, nor did there exist any association of these 4 SNPs
      among groups of patients with 0, 1, 2, and 3-vessel disease (all P > 0.05). Our
      data implicate rs2237892 in KCNQ1 as a protective gene variant against premature
      CAD and we couldn't replicate any association of these 4 SNPs with T2DM or extent
      of coronary lesions in a Chinese population.

PMID- 19575311
TI  - 'Gravida eight, para six, alive two'.

PMID- 19575312
TI  - Cervical length measurement and cervical phosphorylated insulin-like growth
      factor binding protein-1 testing in prediction of preterm birth in patients
      reporting uterine contractions.
AB  - OBJECTIVES: To evaluate the performance of cervical phosphorylated insulin-like
      growth factor binding protein-1 (phIGFBP-1) testing and cervical length
      measurement separately and in combination with physician's clinical judgment in
      prediction of preterm birth among patients with self-reported uterine
      contractions and intact membranes. DESIGN: We enrolled a total of 246 women
      between 22 and 34 weeks of gestation. METHODS: The initial evaluation included
      cervical length measurement using transvaginal ultrasonography. Short cervix was
      defined as <25 mm. A swab sample was obtained from the cervix for phIGFBP-1.
      Admission was used as a clinical marker of an increased risk of preterm delivery
      <or=34 weeks. The diagnostic performances of the tests and clinician's judgment,
      as well as likelihood ratios (LRs) were calculated. MAIN OUTCOME MEASURES:
      Delivery <or=34 weeks and within 14 days. RESULTS: The overall rate of
      spontaneous preterm delivery <or=34 weeks was 4.1% (10/246). Short cervix,
      positive phIGFBP-1 test, combination of both, and clinician's judgment were all
      associated with preterm delivery <or=34 weeks or within 14 days (p<0.01). The
      negative predictive values for delivery <or=34 weeks were 97.4, 97.6, 97.1, and
      98.7%, respectively, and within 14 days 98.7, 99.0, 98.3, and 99.6%,
      respectively. The corresponding positive LRs for delivery <or=34 weeks were 6.8,
      3.8, 75.0, 14.9, and within 14 days 9.7, 5.5, 107.3, 17.1. The negative LRs were
      0.6, 0.6, 0.7, 0.3 and 0.5, 0.3, 0.6, 0.2. CONCLUSION: The rapid phIGFBP-1-test
      has a high negative predictive value for preterm delivery, comparable to that of
      ultrasonographic cervical length measurement.

PMID- 19575307
TI  - Does glomerular hyperfiltration in pregnancy damage the kidney in women with more
      parities?
AB  - OBJECTIVES: We aimed to investigate the glomerular hyperfiltration due to
      pregnancy in women with more parities. METHODS: Five hundred women aged 52.57 +/-
      8.08 years, without a history of hypertension, diabetes mellitus or complicated
      pregnancy were involved in the study. They were divided into three groups. Group
      1: women with no or one parity (n = 76); group 2: women with two or three
      parities (n = 333); group 3: women with four or more parities (n = 91).
      Laboratory parameters and demographical data were compared between the three
      groups. RESULTS: Mean age, serum urea and serum creatinine were similar between
      three groups. Patients in group 3 had significantly higher GFR values compared to
      groups 1 and 2 (109.44 +/- 30.99, 110.76 +/- 30.22 and 121.92 +/- 34.73
      mL/min/1.73 m(2) for groups 1, 2 and 3, respectively; P = 0.008 for group 1 vs
      group 3; P = 0.002 for group 2 vs group 3). CONCLUSIONS: In our study, we suggest
      that glomerular hyperfiltration due to pregnancy does not have adverse effects on
      kidney in women with more parities. Pregnancy may have possible protective
      mechanisms for kidney against adverse effects of glomerular hyperfiltration.

PMID- 19575313
TI  - Clinical comparative study of dose-volume and equivalent uniform  dose based
      predictions in post radiotherapy acute complications.
AB  - BACKGROUND: Single points placed on Dose-Volume Histograms (DVHs) for treatment
      plan acceptance are still widely used compared to the Equivalent Uniform Dose
      (EUD). The aim of this work is to retrospectively measure and compare the ability
      of both criteria in correctly predicting two clinical outcomes, RTOG grade 2
      acute gastrointestinal (GI) and genitourinary (GU) complications in 137 patients
      treated for prostate cancer. MATERIAL AND METHODS: For both complications,the
      best predictions have been achieved by fitting the EUD parameter and a tolerance
      dose (for a varying DVH point) by maximization of the Area Under the Receiver
      Operating Curve (AUROC). A complementary likelihood fitting of the Lyman's Normal
      Tissue Complication Probability (NTCP) allowed a graphical comparison between
      expected and observed frequencies, and to derive the associated parameters.
      RESULTS AND DISCUSSION: No significant differences were found in the AUROC values
      obtained by using dose-volume or EUD criteria, but all the results highlighted
      the role of high doses. Limiting V65 (for grade 2 GI) or V73 (for grade 2 GU) was
      as predictive as limiting EUD value, with n equal to 0.09 or 0.06 respectively,
      but in all cases AUROC values were low (< 0.7). Likelihood fitting gave m = 0.195
      and TD50=72.5 Gy (fixing n=0.06 for acute GU) and m=0.19 and TD50=66 Gy (fixing
      n=0.09 for acute GI). Both AUROC and likelihood values revealed a better fit for
      acute GI than for acute GU. The use of a fractionation correction, new clinical
      contours or previous risk factors could improve these values.

PMID- 19575315
TI  - The social brain hypothesis and its implications for social evolution.
AB  - The social brain hypothesis was proposed as an explanation for the fact that
      primates have unusually large brains for body size compared to all other
      vertebrates: Primates evolved large brains to manage their unusually complex
      social systems. Although this proposal has been generalized to all vertebrate
      taxa as an explanation for brain evolution, recent analyses suggest that the
      social brain hypothesis takes a very different form in other mammals and birds
      than it does in anthropoid primates. In primates, there is a quantitative
      relationship between brain size and social group size (group size is a monotonic
      function of brain size), presumably because the cognitive demands of sociality
      place a constraint on the number of individuals that can be maintained in a
      coherent group. In other mammals and birds, the relationship is a qualitative
      one: Large brains are associated with categorical differences in mating system,
      with species that have pairbonded mating systems having the largest brains. It
      seems that anthropoid primates may have generalized the bonding processes that
      characterize monogamous pairbonds to other non-reproductive relationships
      ('friendships'), thereby giving rise to the quantitative relationship between
      group size and brain size that we find in this taxon. This raises issues about
      why bonded relationships are cognitively so demanding (and, indeed, raises
      questions about what a bonded relationship actually is), and when and why
      primates undertook this change in social style.

PMID- 19575317
TI  - Hematein chelates of unusual metal ions for tinctorial histochemistry.
AB  - Hematoxylin is oxidized easily to hematein, an excellent stain for metal ions. If
      it already is bound to a substrate, the metal ion becomes a mordant linking the
      dye to the substrate. Metal ions added to hematein in solution are chelated by
      the hematein to form a lake. Most of these chelates stain animal tissues. They
      usually are bound to the tissue by a combination of hydrogen bonding of the
      hematein and ionic bonding of the metal ion. When binding of the lake to the
      tissue occurs by way of the metal ion, the metal ion is a mordant. Mordant
      staining often is specific. Chromium hematoxylin binds to strong acids; it can be
      made selective for protein-bound sulfonic acids. Zirconyl hematoxylin is
      selective for acidic mucins. Mucihematein can be made selective for all acidic
      mucins or for sulfomucins alone. Bismuth hematoxylin appears to be selective for
      the guanido group of arginine and there is some evidence that the bonding is
      covalent. Although it is not a histochemical stain, copper-chrome hematoxylin is
      an excellent stain for organelles with double membranes, i.e., mitochondria and
      nuclei.

PMID- 19575316
TI  - ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with
      advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.
AB  - OBJECTIVE: Previously, we scanned all 23,000 human genes for differential
      expression between normal and atherosclerotic tissues and found the involvement
      of ADAM8. METHODS: We investigated the expression of ADAM8 mRNA and protein level
      in human atherosclerotic tissues and non-atherosclerotic internal thoracic
      arteries as well as the association of ADAM8 2662 T/G single nucleotide
      polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk
      of fatal myocardial infarction. RESULTS: ADAM8 mRNA was up-regulated in carotid,
      aortic, and femoral atherosclerotic plaques (n=24) when compared with non
      atherosclerotic arteries. ADAM8 protein expression was increased in advanced
      atherosclerotic plaques as compared to control vessels wherein it was localized
      to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662
      T/G SNP had significantly larger areas of fibrotic, calcified, and complicated
      plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and
      significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal
      pre-hospital MI (P=0.003) than did the TT homozygotes. CONCLUSION: ADAM8 is a
      promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic
      variant significantly associates with advanced atherosclerotic lesion areas and
      MI.

PMID- 19575318
TI  - Implementing metal detector technology and a navigation system in the removal of
      shrapnel.
AB  - INTRODUCTION: The removal of metal shrapnel in the sub-acute phase of casualty
      treatment requires the utmost accuracy in detection and removal, especially when
      there is proximity to major neurovascular structures. Inability to successfully
      locate and remove retained fragments may lead to a variety of complications due
      to fragment migration. In this study we prove the feasibility of a new technique
      which uses metal detector technology combined with a surgical navigation system,
      resulting in improved accuracy and decreased operating time. METHODS: In each of
      the experiments, 6 metal nuts were inserted into a dummy leg to simulate shrapnel
      wounds. Two major experiments were then conducted. Experiment 1 was a comparison
      of two methods: (a) localization of the nuts using surgical navigation alone, and
      (b) localization by means of metal detector technology combined with a surgical
      navigation system (StealthStation(r) TREON(r) plus). Experiment 2 employed the
      same two methods, but this time migration of the metal fragments was introduced.
      The localization time was measured from incision of the dummy skin to the moment
      the metal fragment was touched by the searching device. RESULTS: In experiment 1
      the results showed no significant differences between the two approaches. In
      experiment 2 the new technique was found to significantly decrease the mean
      fragment localization time, taking 9.6 seconds (+/-7.2 seconds) as compared to
      26.4 seconds (+/-13.8 seconds) when using the regular technique. CONCLUSION:
      Combining a metal detector probe and a surgical navigation system was found to
      significantly decrease operating time and increase the surgeon's confidence,
      especially in cases where migration of the metal fragment occurred during
      searching and extraction.

PMID- 19575319
TI  - The need for cross-cultural comparisons.

PMID- 19575320
TI  - Effect of older maternal age on the risk of spontaneous preterm labor: a
      population-based study.
AB  - To determine if older maternal age (35 years and older) at first birth was an
      independent risk factor for spontaneous preterm labor, we conducted a
      retrospective population-based cohort study. Using provincial perinatal data, we
      developed separate risk models for low- and high-risk women using multivariate
      logistic regression. We found that older maternal age exerted a direct and
      independent effect on spontaneous preterm labor for both nulliparous women with
      no preexisting chronic illnesses or pregnancy complications (low-risk) and
      nulliparous women who did not have any preexisting chronic illnesses, but
      developed one or more pregnancy complications (high-risk).

PMID- 19575321
TI  - Women's rights and women's health during HIV/AIDS epidemics: the experience of
      women in sub-Saharan Africa.
AB  - Twenty-five years have passed since HIV/AIDS was recognized as a major public
      health problem. Although billions of dollars are spent in research and
      development, we still have no medical cure or vaccination. In the early days of
      the epidemic, public health slogans suggested that HIV/AIDS does not
      discriminate. Now it is becoming clear that HIV/AIDS spreads most rapidly among
      poor, marginalized, women, colonized, and disempowered groups of people more than
      others. The HIV/AIDS epidemic is exacerbated by the social, economic, political,
      and cultural conditions of societies such as gender, racial, class, and other
      forms of inequalities. Sub-Saharan African countries are severely hit by
      HIV/AIDS. For these countries the pandemic of HIV/AIDS demands the need to travel
      extra miles. My objective in this article is to promote the need to go beyond the
      biomedical model of "technical fixes" and the traditional public health education
      tools, and come up with innovative ideas and strategic thinking to contain the
      epidemic. In this article, I argue that containing the HIV/AIDS epidemic and
      improving family and community health requires giving appropriate attention to
      the social illnesses that are responsible for exacerbating biological disorders.

PMID- 19575322
TI  - Attempted suicide in reproductive age women.
AB  - In this study, we described the frequency of attempted suicide among women of
      reproductive age (10 to 49 years) in a General University Hospital in Ribeirao
      Preto, Brazil (conducted 2005). Relevant comorbidities associated with the
      suicide attempt were calculated. Secondary data were obtained through the
      hospital's records where attempted suicides were reported. Findings revealed 132
      attempted suicides; most women took a toxic substance or their own medication.
      Half of the women previously had attempted suicide. Depression was the most
      frequent psychiatric diagnosis on discharge from the hospital, specifically
      borderline personality disorder, personality disorders axis B and depression
      without association.

PMID- 19575323
TI  - Prevalence of HIV antibodies in pregnant women with increased risk for AIDS.
AB  - The prevalence of Human immunodeficiency virus (HIV) antibodies in pregnant women
      varies widely between industrialized and developing countries. There is a lack of
      information about the status of HIV-infected pregnant women with increased risk
      for AIDS. Our objective was to determine the prevalence of HIV antibodies in
      pregnant women with increased risk at the Hospital of Obstetrics and Gynecology
      of the Mexican Institute of Social Security, Leon, Mexico, from December 18,
      2003, through February 28, 2006. In a cross-sectional study, 2,257 pregnant women
      with at least one risk factor for AIDS were recruited. In these women, a sample
      of blood to determine HIV antibodies was taken. There were two women with
      positive HIV antibodies; therefore, the HIV seroprevalence was 0.8 per 1,000. Of
      the two HIV-positive women, one of them had a history of chronic sexually
      transmitted diseases; she was married to a man who was working outside of our
      country for about 10 months, and also he had tattoos. The other HIV-positive
      woman had a history of chronic sexually transmitted diseases, and her husband had
      intercourse with different women. The risk factors of use of tattoos, migration
      to foreign countries, and use of injectable drugs were more frequent among the
      male partners than in the pregnant women (P < .001). We concluded that in our
      country as well as in other developing countries, the prevalence of HIV
      antibodies in pregnant women with risk factors is low but still present. Because
      a significant number of risk factors for AIDS also were found in their male
      partners, HIV testing should be performed in all pregnant women as well as in
      their male partners.

PMID- 19575324
TI  - A qualitative comparison of women's attitudes toward hysterectomy and myomectomy.
AB  - Hysterectomy is the second most common surgery in the United States, where it is
      practiced at far higher levels than in any other country. There is limited
      understanding however, of why American women choose hysterectomy over other
      treatments. Using a qualitative interview approach, we examined the attitudes of
      18 women who had either a hysterectomy or abdominal myomectomy as a treatment for
      uterine fibroids. From the thematic analysis it is suggested that the two groups
      had different factors affecting their choice of surgery, such as information,
      attitudes toward the reproductive organs, and attitudes toward doctors. It is
      concluded that greater efforts should be made to improve women's access to
      information, and that international comparisons might help to improve our
      understanding of how hysterectomy rates in the United States can be reduced.

PMID- 19575325
TI  - Negotiating participation: how women living with disabilities address barriers to
      exercise.
AB  - Exercise participation among women living with disabilities can be limited as a
      result of pain, decreased muscle strength, and limited mobility. More "disabling"
      than these symptoms, however, is a lack of accessible exercise facilities in
      women's communities. Our study explores how material and social structures and
      functions existing and operating within women's communities and at community
      based exercise facilities affect their participation. Interviews with 15 women
      living with disabilities were conducted and qualitatively analyzed. Participants
      discuss the benefits of their exercise participation, in addition to how they
      experience and negotiate structural and attitudinal barriers within community
      based facilities.

PMID- 19575327
TI  - The role of item similarity in part-list cueing impairment.
AB  - The presentation of a subset of studied items as retrieval cues can have
      detrimental effects on recall of the remaining (target) items. In three
      experiments we examined whether such part-list cueing impairment depends on the
      similarity between cue and target items. Item similarity was manipulated by
      making use of pre-experimental semantic similarities between cue and target items
      (Experiments 1 and 2), or was episodically induced through a similarity-encoding
      task, in which participants were asked to interrelate cue and target items in a
      meaningful way (Experiment 3). In all three experiments reliable part-list cueing
      impairment arose when the similarity between cues and targets was low, but no
      impairment was found when the similarity between cues and targets was high.
      Inhibitory as well as non-inhibitory explanations of the findings are discussed.

PMID- 19575326
TI  - AZT 5'-triphosphate nanoformulation suppresses human immunodeficiency virus type
      1 replication in peripheral blood mononuclear cells.
AB  - Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse
      transcriptase inhibitors (NRTIs) to their active nucleoside 5'-triphosphate
      (NTPs) form is one of the limitations for human immunodeficiency virus (HIV)
      therapy. We report herein direct binding of 3'-azido-3'-deoxythymidine-5'
      triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to
      ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely
      retained its biological activity as assessed by suppression of HIV-1 replication
      in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can
      be used for targeting active NRTIs to the brain by application of an external
      magnetic force and thereby eliminate the brain HIV reservoir and help to treat
      NeuroAIDS.

PMID- 19575328
TI  - Effects of instruction on learners' ability to generate an effective pathway in
      the method of loci.
AB  - One of the most effective mnemonic techniques is the well-known method of loci.
      Learning and retention, especially of sequentially ordered information, is
      facilitated by this technique which involves mentally combining salient loci on a
      well-known path with the material to be learned. There are several variants of
      this technique that differ in the kind of path that is suggested to the user and
      it is implicitly assumed that these variants are comparable in effectiveness. The
      experiments reported in this study were designed to test this assumption. The
      data of two experiments show that participants who are instructed to generate and
      apply loci on a route to their work recall significantly more items in a memory
      test than participants who are instructed to generate and apply loci on a route
      in their house. These results have practical implications for the instruction and
      application of the method of loci.

PMID- 19575329
TI  - Serious gaming and voluntary laparoscopic skills training: a multicenter study.
AB  - This study assesses the issue of voluntary training of a standardized online
      competition (serious gaming) between surgical residents. Surgical residents were
      invited to join a competition on a virtual reality (VR) simulator for
      laparoscopic motor skills. A final score was calculated based on the task
      performance of three exercises and was presented to all the participants through
      an online database on the Internet. The resident with the best score would win a
      lap-top computer. During three months, 31 individuals from seven hospitals
      participated (22 surgical residents, 3 surgeons and six interns). A total of 777
      scores were logged in the database. In order to out-perform others some
      participants scheduled themselves voluntarily for additional training. More
      attempts correlated with higher scores. The serious gaming concept may enhance
      voluntary skills training. Online data capturing could facilitate monitoring of
      skills progression in surgical trainees and enhance (VR) simulator validation.

PMID- 19575330
TI  - The complete mitochondrial genome of the RR-B strain of swordtail (Xiphophorus
      helleri).
AB  - BACKGROUND AND AIMS: The swordtail (Xiphophorus helleri) has been used in studies
      of behavior, phylogenetics, genetics, physiology, cell biology, cancer research,
      and biomedicine. Mitochondrial DNA (mtDNA) studies are of pressing need in order
      to assess the population history of the species. MATERIALS AND METHOD: In this
      study, we present the complete mtDNA genome sequence of two specimens: one from a
      RR-B strain, a 27-generation inbred line; and one non-selective swordtail with
      red eyes and red body color from the Guangzhou market, measuring 16,638 and
      16,635 bp, respectively. RESULTS: The genome comprises 13 protein-coding genes,
      22 tRNAs, two rRNAs and a major non-coding region. The comparison of the two
      specimens' mitogenomes revealed a relatively low number (57) of single nucleotide
      polymorphisms-29 located in protein-coding genes, 11 in rRNA genes, six in tRNA
      genes, and six in the non-coding region. CONCLUSION: We present an important
      genetic resource for the RR-B strain of swordtails and swordtail species in
      general.

PMID- 19575331
TI  - Adipose tissue is not an important source for matrix metalloproteinase-9 in the
      circulation.
AB  - OBJECTIVES: Matrix metalloproteinase 9 (MMP-9) is overexpressed in
      atherosclerotic plaques and in many cancers, and has emerged as a potential
      circulating biomarker for such diseases. However, adipose tissue (AT) might also
      produce circulating MMP-9, thereby reducing the value of MMP-9 as a biomarker.
      The aim of this study was to evaluate the impact of AT on circulating MMP-9, and
      if the metabolic syndrome might have a modifying effect. METHODS: Gene expression
      of MMP-9 was measured in AT, isolated adipocytes, atherosclerotic plaques,
      macrophages and various other human tissues using real-time PCR. Relationships
      between plasma MMP-9 (ELISA), adiposity, and metabolic syndrome were analyzed in
      a population-based cohort of 61-year-old men (n=513). Both AT mRNA levels and
      circulating levels of MMP-9 were measured in obese subjects (n=40) with and
      without the metabolic syndrome, treated with a weight-reducing diet. RESULTS:
      Bone marrow, atherosclerotic plaques and macrophages had considerably higher MMP
      9 mRNA than subcutaneous AT and isolated adipocytes. Among the 61-year-old men,
      active plasma MMP-9 concentrations were associated with several metabolic
      syndrome factors, and inflammatory markers, but not body mass index (BMI). In
      obese patients with, but not without metabolic syndrome AT mRNA levels and
      circulating MMP-9 declined during weight reduction, but there was no association
      between changes in plasma MMP-9 and BMI. CONCLUSION: The results show that
      adipose tissue per se is not associated with circulating MMP-9. Components of the
      metabolic syndrome, such as circulating insulin and glucose were related to
      plasma MMP-9 both in the observation and dietary weight loss studies.

PMID- 19575333
TI  - Frequency of successful intra-articular puncture of the sternoclavicular joint: a
      cadaver study.

PMID- 19575332
TI  - Health-related quality of life in patients with primary Sjogren's syndrome:
      relationship with serum levels of proinflammatory cytokines.
AB  - OBJECTIVE: A cross-sectional study of 30 patients with primary Sjogren's syndrome
      (pSS) was performed to analyse the health-related quality of life and its
      relationship with serum levels of macrophage- and lymphocyte-derived cytokines.
      PATIENTS AND METHODS: Health-related quality of life was evaluated using the 36
      item Short Form Health Survey (SF-36). Serum levels of interleukin (IL)-1beta, IL
      6, IL-10, tumour necrosis factor (TNF)-alpha, and gamma-interferon (gamma-INF)
      were analysed by a sandwich immunoassay-based protein array system. RESULTS: Each
      of the eight scales of the SF-36 evaluating quality of life, as well as the
      physical composite score (PCS) and the mental composite score (MCS), showed a
      decrease in pSS patients. Similarly, patients with pSS showed significantly
      increased concentrations of each of the five cytokines analysed, when compared
      with the healthy control group (n = 20). In pSS patients, a significant negative
      correlation was detected between serum levels of IL-6 and the PCS of the SF-36.
      Those patients with concentrations of IL-6 higher than those of the healthy
      controls showed a significantly lower score in the dimensions of bodily pain and
      physical functioning, and in the PCS. CONCLUSIONS: Patients with pSS showed
      increased levels of several macrophage- and lymphocyte-derived cytokines,
      indicating the existence of an immune activation state. Serum levels of one of
      these cytokines, IL-6, were correlated with poor quality of life in these
      individuals.

PMID- 19575334
TI  - Elimination of the enhanced Simon effect for older adults in a three-choice
      situation: ageing and the Simon effect in a go/no-go Simon task.
AB  - In a Simon task, participants show better performance when the irrelevant
      stimulus location corresponds with the response location than when it does not,
      and this effect is typically greater for older adults than for younger adults. To
      study the effect of cognitive ageing in the Simon task, we compared young and old
      adults using two versions of the Simon task: (a) a standard visual Simon task,
      for which participants respond with left and right key-presses to the red and
      green colours of stimuli presented in left and right locations; (b) a go/no-go
      version of the Simon task, which was basically the same, except that the shape of
      the stimulus in one third of the trials indicates that no response is to be made.
      In both tasks, both age groups showed the Simon effect. The magnitude of the
      effect for the standard Simon task was greater for the older adults than for the
      younger adults. Nevertheless, the two groups showed an equivalent Simon effect in
      the go/no-go version of the Simon task. Reaction time distribution analyses
      revealed basically similar functions for both age groups: a decreasing pattern of
      the Simon effect in the standard task and an increasing pattern of the effect in
      the go/no-go version of the task. The results suggest that older adults find it
      more difficult to suppress an automatic activation of the corresponding response,
      though this automatic activation was reduced in situations where the response was
      frequently inhibited.

PMID- 19575335
TI  - Antidepressants: controversies about their efficacy in depression, their effect
      on suicidality and their place in a complex psychiatric treatment approach.
AB  - The paper will highlight and discuss some of the important issues and
      controversies of current depression treatment like the efficacy of
      antidepressants, their effect on suicidality, their place in a complex
      psychiatric treatment strategy including psychotherapy and other psychosocial
      activities. The efficacy of antidepressants is clinically significant, but often
      monotherapy with one drug has to be followed by others or by
      comedication/augmentation therapy approaches. Psychosocial therapy, predominantly
      focused on psychotherapeutic strategies, can also contribute in a relevant way to
      the therapeutic success. Generally, antidepressants reduce suicidality, but under
      special conditions like young age or personality disorder, they can also be
      harmful in this respect. However, under the conditions of good clinical practice,
      the risk-benefit relationship of treatment with antidepressants can be judged as
      favourable. In addition, the paper tries to analyse the question about how to
      reach individualised, evidence and value oriented decision making in the complex
      treatment of depressive patients. The capacity of psychiatrists to individualise
      treatment decisions in terms of "the right drug/treatment for the right patient"
      is still restricted since there are currently not enough powerful clinical or
      biological predictors, which help to achieve this goal. There is hope that in
      future pharmacogenetics will contribute significantly to a personalised
      treatment. The ideal that all steps of classical decision making can be based on
      the strict rule of evidence-based medicine is far away from reality.
      Individualised decision making is so complex that the rigorous expectations of
      evidence-based medicine can hardly be fulfilled. Finally, it should be considered
      that clinical decision making is not only evidence but also value oriented.

PMID- 19575339
TI  - [Research in psychotherapy--does it improve psychosomatic care?].

PMID- 19575341
TI  - [Traumatic experiences in patients with psychosis: more arguments against the
      "bio-bio-bio Model"].

PMID- 19575342
TI  - [Differentiation of nursing tasks in psychiatric wards through new professions
      and additional training].

PMID- 19575343
TI  - [Seasonal dependence of the parameters of quantitative ultrasonic measurements on
      the peripheral skeleton].
AB  - PURPOSE: To investigate the dependence of parameters of quantitative ultrasound
      (QUS) on seasonable temperature variation. MATERIAL AND METHODS: 10 adolescents
      were examined by QUS at the heel (Sahara, Hologic), at the tibia, at the radius
      and at the proximal phalanges (Omnisense 7000 P, Sunlight). Measuring took place
      0 (T1), 30 (T2), 60 (T3), and 120 (T4) minutes after entering the building at
      constant room temperature. The skin temperature was measured. The speed of sound
      (SOS; m/s) and the broadband ultrasound attenuation (BUA; dB/MHz) were determined
      as QUS parameters. Investigations took place every two weeks from January to
      July. RESULTS: Between skin temperature at the heel after entering the building
      and the measured SOS at the point of time (T1), a significantly negative
      correlation was stated (R = -0.47; p < 0.01); after 30 minutes (T2) the
      correlation was R = -0.21 (p < 0.01); after 60 minutes (T3) and after 120 minutes
      (T4) the correlation was not significantly anymore (R = -0,1). Minor, significant
      correlation was stated at the proximal phalanx at point of time T 1 (R = -0.2; p
      < 0.01). There was no significant correlation between temperature and SOS at the
      radius and tibia. CONCLUSION: The speed of sound at the heel depends inversely on
      outside temperature. This effect decreases with the longer duration of stay in
      the building. The measuring error is not relevant in relation to the population
      variability, but should be considered for individual process controls. There is
      no temperature dependence for the broadband ultrasonic attenuation. The SOS on
      the radius and tibia does not depend on temperature.

PMID- 19575344
TI  - [Onyx (ethylene-vinyl-alcohol-copolymer)--a novel approach to the endovascular
      treatment of acute bleeding].
AB  - PURPOSE: The purpose of our retrospective study was to determine the feasibility
      and efficacy of the endovascular embolization of peripheral acute arterial
      hemorrhage using Onyx. MATERIALS AND METHODS: Between October 2003 and February
      2007, 14 patients with acute arterial bleeding underwent percutaneous arterial
      embolization using Onyx. Bleeding was caused by iatrogenic vessel injury (6
      patients), malignancy/inflammation (5 patients) and trauma (3 patients).
      Hematomas were located in the pelvis (5 patients), followed by liver (3
      patients), retroperitoneal space (2 patients), thorax (2 patients), pancreas (1
      patient), and thigh (1 patient). The number of embolized arteries, the volume and
      viscosity of embolic agent (Onyx), the number of additionally used coils, the
      embolization time, and the technical and clinical outcome were documented.
      Procedure-related complications, recurrent bleeding during hospital stay and
      outcome were recorded. RESULTS: In 14 patients selective endovascular
      embolization of 15 arteries was performed. The average volume of injected Onyx
      was 1.3 +/- 0.8 ml. In 6 cases (42.9%) Onyx was used in conjunction with coils.
      The average time between the correct placement of microcatheter and complete
      embolization was 24.9 +/- 12.6 minutes. In 13 of 14 patients (92.8%),
      embolization was technically successful. In one case, procedure-related
      complications occurred and embolization was performed in a second session a day
      later. After technically successful embolization, no recurrent bleeding occurred
      during hospitalization. Out of 14 patients, six (42.9%) died 1 - 38 days after
      technically successful embolization due to multiple organ failure (2 patients),
      hypoxic brain injury (2 patients), septic shock (1 patient) or malignancy
      associated death (1 patient). CONCLUSION: We conclude that transcatheter
      embolization with the new liquid embolic agent Onyx is technically feasible and
      effective in patients with acute arterial hemorrhage.

PMID- 19575345
TI  - [Pneumocytoma--young patient with a rare lung tumor].

PMID- 19575346
TI  - [Unusual speech dominance in a stroke patient].

PMID- 19575347
TI  - ["The world epidemic situation changes." Interview by Stephanie Hugler].

PMID- 19575348
TI  - Oxyma: an efficient additive for peptide synthesis to replace the benzotriazole
      based HOBt and HOAt with a lower risk of explosion.
AB  - Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] has been tested as an additive for
      use in the carbodiimide approach for formation of peptide bonds. Its performance
      in relation to those of HOBt and HOAt, which have recently been reported to
      exhibit explosive properties, is reported. Oxyma displayed a remarkable capacity
      to inhibit racemization, together with impressive coupling efficiency in both
      automated and manual synthesis, superior to those of HOBt and at least comparable
      to those of HOAt, and surpassing the latter coupling agent in the more demanding
      peptide models. Stability assays showed that there was no risk of capping the
      resin under standard coupling conditions. Finally, calorimetry assays (DSC and
      ARC) showed decomposition profiles for benzotriazole-based additives that were
      consistent with their reported explosivities and suggested a lower risk of
      explosion in the case of Oxyma.

PMID- 19575349
TI  - From polymer to size-defined oligomers: a step economy process for the efficient
      and stereocontrolled construction of chondroitin oligosaccharides and
      biotinylated conjugates thereof: part 1.
AB  - Controlled acid hydrolysis of polymeric chondroitin sulfate of bovine origin
      afforded in good yield a basic disaccharide fragment that was used for the first
      time as a starting material for the expeditious preparation of a set of building
      blocks that in turn act as versatile synthons for the efficient and
      stereocontrolled construction of a collection of size-defined chondroitin
      oligomers (from di- to octasaccharides). This step economy process allows their
      preparation as reducing species, fitted with a fluorophore, or as biotinylated
      conjugates; all useful tools for the preparation of microarrays, or as probes for
      the study of the biosynthesis of chondroitin sulfate.

PMID- 19575350
TI  - Diiron proton reduction catalysts possessing electron-rich and electron-poor
      naphthalene-1,8-dithiolate ligands.
AB  - The diiron complexes [Fe(2)(CO)(6)(1,8-S(2)-2,4,5,7-Cl(4)C(10)H(2))] (3),
      [Fe(2)(CO)(6)(1,8-S(2)C(10)H(6))] (4), and [Fe(2)(CO)(6)(1,8-S(2)-2,7
      tBu(2)C(10)H(4))] (5) were synthesized in moderate yield from naphthalene-1,8
      dithiols and [Fe(3)(CO)(12)]. They were characterized by IR, (1)H and (13)C NMR
      spectroscopy and 3 and 4 were characterized by X-ray crystallography. They
      contain a butterfly Fe(2)S(2) core with Fe-Fe distances of 2.529(1) (3) and
      2.506(1) A (4). Cyclic voltammetry (CH(2)Cl(2)/nBu(4)PF(6)) revealed two one
      electron reductions, at potentials more positive than those for the related
      [Fe(2)(CO)(6)(S(CH(2))(3)S)] (1), and one one-electron oxidation. The first
      reduction of the electron poor 3 (-1.60 V vs Fc/Fc(+)) is 240 mV more positive
      than the first reduction of the electron rich 5 (-1.84 V). Electrochemical
      studies revealed that 3-5 facilitate the proton reduction of p-toluenesulfonic
      acid. The rates of catalysis, with a 95% confidence limit, are 2.4+/-0.8 (1),
      5.2+/-0.8 (3), 3.1+/-1.1 (4), 2.9+/-0.6 (5), and 4.5+/-0.2 h(-1) for the related
      [Fe(2)(CO)(6)(1,2-S(2)C(6)H(4))]. The rates were determined by bulk electrolysis
      at -1.70 V (Fc/Fc(+)), which correspond to an overpotential of 1.05 V for p
      toluenesulfonic acid.

PMID- 19575351
TI  - Regioselective Ru-catalyzed direct 2,5,8,11-alkylation of perylene bisimides.

PMID- 19575352
TI  - Imaging of catenated, figure-of-eight, and trefoil knot polymer rings.

PMID- 19575353
TI  - Hospitalizations are increasing among minority patients with Crohn's disease and
      ulcerative colitis.
AB  - BACKGROUND: Rates of inflammatory bowel disease (IBD) appear to be increasing
      among nonwhite populations outside the United States, but national data
      describing the incidence and prevalence of IBD are not available for minority
      patients. The aim of this study was to examine time trends of hospital discharge
      among minority patients with IBD. METHODS: Nationally representative data
      describing hospital discharges were obtained from the National Hospital Discharge
      Survey for the years 1994 to 2006. Race-specific annual proportions of
      hospitalizations including a discharge diagnosis of ulcerative colitis and
      Crohn's disease were calculated. Trends in proportions were assessed for
      statistical significance using the extended Mantel-Haenszel chi-square test for
      trend. RESULTS: The proportion of hospitalizations including a discharge
      diagnosis of IBD increased significantly from 1994 to 2006 among the total
      population and among Asian, black, and white patients separately. Increases were
      statistically significant when analysis was performed for Crohn's disease and
      ulcerative colitis combined and separately. Marked increases were seen among
      Asians. CONCLUSIONS: The proportion of hospitalizations including a discharge
      diagnosis of IBD increased significantly among minority and nonminority patients
      from 1994 through 2006. The causes underlying these changes are not certain and
      should be further investigated.

PMID- 19575354
TI  - Does methotrexate induce mucosal healing in Crohn's disease?

PMID- 19575355
TI  - Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine,
      and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) level in patients with
      inflammatory bowel diseases.
AB  - BACKGROUND: Intestinal microvessels of patients with inflammatory bowel disease
      (IBD) show microvascular endothelial dysfunction. It may contribute to reduced
      perfusion, poor ulcer healing, and sustained chronic inflammation. The aim of the
      study was to assess endothelial dysfunction and oxidative stress markers in
      patients with IBD. METHODS: Serum levels of asymmetric dimethylarginine (ADMA),
      symmetric dimethylarginine (SDMA), arginine, and 8-iso-prostaglandin F2alpha (8
      iso-PGF2alpha) were measured in 31 consecutive patients with ulcerative colitis
      (UC) and 32 with Crohn's disease (CD). Apparently healthy subjects served as age-
      and sex-matched controls. Associations between these markers and the disease
      activity and laboratory variables were evaluated. RESULTS: ADMA, SDMA, and 8-iso
      PGF2alpha levels were increased in the IBD group as compared to the control group
      and higher in patients with CD than UC (P < 0.05 for all comparisons). Arginine
      levels were similar in all the groups. In the CD and UC groups ADMA and SDMA
      showed positive correlation with 8-iso-PGF2alpha (r from 0.47-0.67; P < 0.01 for
      all comparisons). ADMA and SDMA correlated positively with the CD activity (r =
      0.4, P = 0.025; r = 0.4, P = 0.024, respectively) and the 8-iso-PGF2alpha level
      correlated positively with the UC activity (r = 0.4, P = 0.026). CONCLUSIONS:
      This is the first study to show that in patients with IBD there is enhanced ADMA
      generation that might be associated with oxidative stress, and these effects are
      more pronounced in the CD group.

PMID- 19575356
TI  - Psychosocial symptoms and competence among adolescents with inflammatory bowel
      disease and their peers.
AB  - BACKGROUND: The aim was to evaluate psychosocial symptoms and competence as
      reported by the parents and the adolescents themselves among patients with
      inflammatory bowel disease (IBD) in relation to population-based controls.
      METHODS: Standardized Achenbach questionnaires-Child Behavior Checklist (CBCL)
      for the parents and Youth Self-Report (YSR) for the adolescents-were sent to
      Finnish families of adolescents with IBD (age 10-18 years), and their controls
      matched for age, gender, and place of residence. The final study group comprised
      160 adolescents with IBD and 236 controls with their parents, respectively.
      RESULTS: According to parent reports, adolescents with IBD had more symptoms of
      anxious/depressed mood (P < 0.001), withdrawn/depressed mood (P < 0.05), social
      problems (P < 0.05), thought problems (P < 0.001), somatic complaints (P <
      0.001), and lower competence (P < 0.05) than population-based controls.
      Unexpectedly, there was no group difference in the amount of self-reported
      psychosocial symptoms, somatic complaints, or competence between adolescents with
      IBD and their peers. However, adolescents with severe IBD reported significantly
      more emotional problems (P < 0.001) than those with mild symptoms or controls.
      CONCLUSIONS: According to parents, adolescents with IBD have more emotional
      problems, social problems, thought problems, and lower competence than their
      population-based peers. Self-perceived severity of the IBD symptoms is associated
      with a larger amount of parent and self-reported emotional symptoms.
      Complementary methods should be used while assessing the psychosocial well-being
      of adolescents with IBD as questionnaires alone may be insufficient.

PMID- 19575357
TI  - Factors predicting the outcome of disease activity assessment in Crohn's disease.
AB  - BACKGROUND: The Crohn's Disease Activity Index (CDAI) has become the gold
      standard for assessment of disease activity in CD. This study investigated the
      relationship between CDAI and the physicians' global assessment of disease
      activity (PGA) and whether different demographic and disease-related factors
      predict the outcome. METHODS: Multiple linear regression analysis was used to
      investigate the relationship between CDAI and PGA obtained from 405 CD patients.
      Predictors of the CDAI and the PGA outcome were identified. RESULTS: The
      correlation between CDAI and PGA was moderate. In patients with CDAI >150, 72% of
      the total score were derived from the subjective variables. The regression
      coefficients were not significant for 3 of the CDAI variables. In regression
      analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection,
      concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was
      predicted only by CRP, stenosis, and fistula. CONCLUSIONS: The correlation
      between CDAI and PGA was moderate and the subjective variables had a high impact
      on CDAI. Factors with no obvious relation to inflammatory activity predicted the
      outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective
      (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables
      should be considered in the assessment of disease activity.

PMID- 19575358
TI  - Cerebral venous thrombosis in inflammatory bowel diseases.

PMID- 19575359
TI  - Comparison of several activity indices for the evaluation of endoscopic activity
      in UC: inter- and intraobserver consistency.
AB  - BACKGROUND: This study evaluated inter- and intraobserver agreement in the
      assessment of ulcerative colitis (UC) activity using 4 established indices and a
      newly designed Modified 6-point Activity Index. METHOD: In all, 279 endoscopic
      pictures of inflammatory lesions from 93 UC patients were displayed twice to 4
      expert and 4 trainee endoscopists, at an interval of 1 month. Each picture was
      assessed for inflammatory changes using established indices (Matts, Schroeder
      [a.k.a. Mayo Score], Baron, and Blackstone) and our new Modified 6-point Activity
      Index. Weighted kappa statistics were used to estimate intra- and interobserver
      variation. RESULTS: The Matts and Schroeder indices gave a "good" degree of
      concordance for expert endoscopists in terms of inter- and intraobserver
      agreements (0.74-0.78); this was not so evident with the Baron and Blackstone
      indices (0.61-0.73). For trainee endoscopists, all scores for inter- and
      intraobserver weighted kappa values using established indices (0.41-0.51) were
      lower than for the experts. The degree of concordance using the Modified 6-point
      Activity Index was rated as "good" for inter- and intraobserver agreements for
      expert endoscopists (0.65 and 0.79), and as "moderate" for trainee endoscopists
      (0.54 and 0.64). CONCLUSIONS: Accurate assessment of UC disease activity from
      endoscopic findings benefited from experience. For expert endoscopists, the Matts
      and Schroeder indices proved the most reliable of the 4 established indices.
      Current endoscopic technologies may be adequate for assessing UC activity,
      particularly if modified to permit a finer classification of disease severity
      based on 6 grades, as with our newly developed Modified 6-point Activity Index.

PMID- 19575360
TI  - Crohn's disease is associated with restless legs syndrome.
AB  - BACKGROUND: Extraintestinal manifestations of Crohn's disease (CD) have not
      previously included the central nervous system (CNS). Restless legs syndrome
      (RLS) is a CNS disorder that is either idiopathic or secondary to a number of
      diseases. The aim of this study was to determine if RLS was associated with CD
      because both are associated with iron deficiency, inflammation, and bacterial
      overgrowth. METHODS: Consecutive CD outpatients (N = 272) were prospectively
      surveyed at 4 centers for criteria for RLS. Incidence (having RLS at any point in
      time), prevalence (having RLS at time of survey), clinical characteristics, risk
      factors, and potential qualitative relationship between RLS and gastrointestinal
      symptoms were queried. RESULTS: The incidence of RLS in patients with CD was
      42.7%. Prevalence was 30.2% compared with 9% of spouses. CD patients with and
      without RLS had a mean age of 46.8 versus 42.6 years, small intestine involvement
      in 77.9% versus 66.7%, colon involvement in 39.7% versus 63.2%, and prior iron
      deficiency anemia in 49.3% versus 33.1%. There was no difference between the CD
      groups with respect to current iron deficiency, RLS family history, or rare
      prevalence of concomitant RLS disorders. In 91.8% of patients with RLS and CD,
      RLS started during or after the onset of CD diagnosis. Among 73 patients with
      RLS, 67 (44.5%) stated there was a relationship between qualitative RLS symptom
      improvement with overall CD symptom improvement. CONCLUSIONS: These results
      demonstrate that RLS occurs frequently in CD and appears to be a possible
      extraintestinal manifestation. The potential relationship of RLS with CD activity
      warrants further investigation.

PMID- 19575361
TI  - Role of ATG16L1 Thr300Ala polymorphism in inflammatory bowel disease: a Study in
      the Spanish population and a meta-analysis.
AB  - BACKGROUND: Thr300Ala polymorphism in ATG16L1 was reported as a susceptibility
      factor to Crohn's disease (CD). Inconsistently replicated associations with
      ulcerative colitis (UC) and specifically with ileal CD were also reported. Our
      aims were: to replicate the ATG16L1 Thr300Ala association with inflammatory bowel
      disease (IBD) in the Spanish population, to perform a meta-analysis to determine
      the risk conferred to the different IBD subgroups, and to test for the
      interaction with CARD15 or IL23R risk loci. METHODS: Thr300Ala (rs2241880) single
      nucleotide polymorphism (SNP) was genotyped in 712 IBD patients and 745 controls
      by TaqMan technology. Genetic frequencies were compared with chi-square tests.
      Our findings were pooled in a meta-analysis. RESULTS: In Spain, we observed an
      association of rs2241880 with CD (P = 0.008; odds ratio [OR, 95% confidence
      interval, CI] = 1.28 [1.06-1.54]), but not with UC. No significant differences
      emerged when patients were stratified by clinical features. Similarly, the meta
      analysis demonstrated a significant association only with CD (P < 10(-4); OR [95%
      CI] = 1.33 [1.28-1.38]). A significant difference between ileal CD patients and
      controls was observed, but heterogeneity was found in comparisons involving
      colonic CD patients and definite conclusions cannot be drawn. No interaction
      between rs2241880 and the established CARD15 or IL23R susceptibility variants was
      observed. CONCLUSIONS: The Thr300Ala polymorphism is associated with CD,
      regardless of the CARD15 or IL23R status, but not with UC. Stratification by
      clinical phenotypes did not show definitive results because of the existing
      heterogeneity among studies.

PMID- 19575362
TI  - Elevated serum chromogranin A in irritable bowel syndrome (IBS) and inflammatory
      bowel disease (IBD): a shared model for pathogenesis?

PMID- 19575364
TI  - Sustained virological response to interferon plus ribavirin reduces liver-related
      complications and mortality in patients coinfected with human immunodeficiency
      virus and hepatitis C virus.
AB  - Human immunodeficiency virus (HIV) infection modifies the natural history of
      chronic hepatitis C, thus promoting more rapid progression to cirrhosis and end
      stage liver disease. The objective of our study was to determine whether
      hepatitis C virus (HCV) clearance is associated with improved clinical outcomes
      in patients positive for HIV and HCV. It was an ambispective cohort study carried
      out in 11 HIV units in Spain and involved 711 consecutive patients positive for
      HIV/HCV who started interferon plus ribavirin therapy between 2000 and 2005. We
      measured sustained virologic response (SVR), i.e., undetectable HCV RNA at 24
      weeks after the end of treatment, and clinical outcomes, defined as death (liver
      related or non-liver-related), liver decompensation, hepatocellular carcinoma,
      and liver transplantation. Of 711 patients who were positive for HIV/HCV, 31% had
      SVR. During a mean follow-up of 20.8 months (interquartile range: 12.2-38.7), the
      incidence rates per 100 person-years of overall mortality, liver-related
      mortality, and liver decompensation were 0.46, 0.23, and 0.23 among patients with
      SVR and 3.12, 1.65, and 4.33 among those without SVR (P = 0.003, 0.028, and
      <0.001 by the log-rank test), respectively. Cox regression analysis adjusted for
      fibrosis, HCV genotype, HCV RNA viral load, Centers for Disease Control and
      Prevention clinical category, and nadir CD4+ cell count showed that the adjusted
      hazard ratio of liver-related events was 8.92 (95% confidence interval, 1.20;
      66.11, P = 0.032) for nonresponders in comparison with responders and 4.96 (95%
      confidence interval, 2.27; 10.85, P < 0.001) for patients with fibrosis grade of
      F3-F4 versus those with F0-F2.Because this was not a prospective study, selection
      and survival biases may influence estimates of effect. CONCLUSION: Our results
      suggest that the achievement of an SVR after interferon-ribavirin therapy in
      patients coinfected with HIV/HCV reduces liver-related complications and
      mortality.

PMID- 19575363
TI  - Autophagy at the gut interface: mucosal responses to stress and the consequences
      for inflammatory bowel diseases.
AB  - Autophagy is a conserved homeostatic process by which cells degrade and recycle
      cytoplasmic contents and organelles. Recently, autophagy has come to prominence
      as a factor in many disease states, including inflammatory bowel diseases. In
      this review we explore the recent discoveries in autophagy and how these relate
      to the special conditions experienced by the gut mucosa. We will pay particular
      attention to autophagy as an innate immune process and its role in the
      development and education of the adaptive immune system.

PMID- 19575365
TI  - Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine
      production.
AB  - The mechanisms mediating hepatic accumulation of inflammatory cells in
      cholestatic liver disease remain enigmatic. Our thesis is that Hedgehog (Hh)
      pathway activation promotes hepatic accumulation of immune cells that interact
      with cholangiocytes. We believe that myofibroblastic hepatic stellate cells (MF
      HSCs) release soluble Hh ligands that stimulate cholangiocytes to express
      chemokines that recruit mononuclear cell types with cognate receptors for these
      chemokines, thereby orchestrating a repair-related mechanism for liver
      inflammation. To address this thesis, we used three experimental systems that
      allow the definition of Hh-dependent mechanisms that induce phenotypic changes in
      cholangiocytes. First, cholangiocytes were cultured alone or in the presence of
      Hh-producing MF-HSCs in a transwell coculture system and/or treated with MF-HSC
      conditioned medium with or without Hh-neutralizing antibodies. Changes in the
      cholangiocyte phenotype were then evaluated by microarray analysis, quantitative
      reverse-transcriptase polymerase chain reaction (QRT-PCR), and/or enzyme-linked
      immunosorbent assay for chemokine (C-X-C) motif ligand 16 (Cxcl16). Bile duct
      ligation was chosen to model biliary fibrosis in mice with an overly active Hh
      pathway, control littermates, and healthy rats, and the gene profile was
      evaluated by QRT-PCR in whole liver tissue. Second, a transwell chemotaxis assay
      was used to examine natural killer T (NKT) cell migration in response to
      cholangiocytes and particularly cholangiocyte-derived Cxcl16. Finally, we studied
      liver samples from primary biliary cirrhosis patients and controls by QRT-PCR to
      compare differences in the Hh pathway and Cxcl16. Co-immunostaining of
      cytokeratin-7 and Cxcl16 was then performed to localize the phenotypic source of
      Cxcl16. We found that MF-HSCs release soluble Hh ligands that stimulate
      cholangiocytes to produce Cxcl16 and recruit NKT cells. Hh pathway activation
      during cholestatic liver injury also induces cholangiocyte expression of Cxcl16.
      CONCLUSION: During biliary injury, Hh pathway activation induces cholangiocyte
      production of chemokines that recruit NKT cells to portal tracts.

PMID- 19575367
TI  - Combination of fibrosis tests: sequential or synchronous?

PMID- 19575366
TI  - Individualized treatment strategy according to early viral kinetics in hepatitis
      C virus type 1-infected patients.
AB  - Individualized treatment on the basis of early viral kinetics has been discussed
      to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection.
      Individually tailored reduction in treatment duration in HCV type 1-infected
      patients represents one possible strategy. Four hundred thirty-three patients
      were randomly assigned to receive either 1.5 microg/kg peginterferon alfa-2b
      weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an
      individually tailored treatment duration (18-48 weeks; n = 208, group B). In the
      latter group, treatment duration was calculated using the time required to induce
      HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL)
      multiplied by the factor 6. All bDNA negative samples were retested with the more
      sensitive transcription-mediated amplification (TMA) assay (sensitivity limit,
      5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in
      group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7%
      versus 14.2% [P< 0.0005]). Important predictors of response were the levels of
      baseline viremia as well as the time to TMA negativity on treatment. Taking the
      simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative
      TMA test within the first 4 weeks as predictors for treatment response, SVR rates
      were comparable between both treatment schedules with an SVR probability of >80%
      obtained in patients treated for only 18 or 24 weeks. CONCLUSION: The
      individualized treatment strategy according to time to bDNA negativity failed to
      provide comparable efficacy compared with the standard of care. The inferiority
      of the individualized protocol may be explained by the use of a less sensitive
      HCV RNA assay, and also by underestimation of the importance of baseline viremia.

PMID- 19575368
TI  - Folding and unfolding of two mixed alpha/beta peptides.
AB  - We present a molecular dynamics simulation study of two peptides containing alpha
      and beta-amino acid residues. According to experiment, the two peptides differ
      in the dominant fold when solvated in methanol: one shows a helical fold, the
      other a beta hairpin. The simulations at 300 and 340 K were done by starting from
      a NMR spectroscopic model structure and from an extended (denatured) structure.
      The typical structural features of the two peptides are reproduced and a
      folding/unfolding equilibrium is observed on the nanosecond timescale at 300 K.
      Analysis of proton-proton NOE distance bounds and backbone (3)J coupling
      constants gives results consistent with the experimental data. We conclude that
      our simulations are complementary to the experiments by providing detailed
      information on the conformational distributions.

PMID- 19575369
TI  - Biosynthesis of 2-hydroxy and iso-even fatty acids is connected to sphingolipid
      formation in myxobacteria.
AB  - 2-Hydroxy fatty acids can be found in several different organisms, including
      bacteria. In this study, we have studied the biosynthesis of 2-hydroxy fatty
      acids in the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca,
      resulting in the identification of a family of stereospecific fatty acid alpha
      hydroxylases. Although the stereospecificities of the hydroxylases differ between
      these two species, they share a common function in supporting fatty acid alpha
      oxidation; that is, the oxidative shortening of fatty acids. Whereas in S.
      aurantiaca this process takes place during normal vegetative growth, in M.
      xanthus it takes place only under developmental conditions. We were also able to
      identify serine palmitoyltransferase encoding genes involved in sphingolipid
      biosynthesis as well as sphingolipids themselves in both types of myxobacteria,
      and were able to show that the alpha-hydroxylation reaction is in fact dependent
      on the presence of fatty acids bound to sphingolipids.

PMID- 19575370
TI  - Inversion of the configuration of a single stereocenter in a beta-heptapeptide
      leads to drastic changes in its interaction with phospholipid bilayers.

PMID- 19575371
TI  - STD-NMR studies suggest that two acceptor substrates for GlfT2, a bifunctional
      galactofuranosyltransferase required for the biosynthesis of Mycobacterium
      tuberculosis arabinogalactan, compete for the same binding site.
AB  - The mycobacterial cell wall is a complex architecture, which has, as its major
      structural component, a lipidated polysaccharide covalently bound to
      peptidoglycan. This structure, termed the mycolyl-arabinogalactan-peptidoglycan
      complex, possesses a core galactan moiety composed of approximately 30
      galactofuranosyl (Galf) resides attached via alternating beta-(1-->6) and beta-(1
      ->5) linkages. Recent studies have shown that the entire galactan is synthesized
      by the action of only two bifunctional galactofuranosyltransferases, GlfT1 and
      GlfT2. We report here saturation-transfer difference (STD) NMR spectroscopy
      studies with GlfT2 using two trisaccharide acceptor substrates, beta-D-Galf-(1-
      >6)-beta-D-Galf-(1-->5)-beta-D-Galf-O(CH(2))(7)CH(3) (2) and beta-D-Galf-(1-->5)
      beta-D-Galf-(1-->6)-beta-D-Galf-O(CH(2))(7)CH(3) (3), as well as the donor
      substrate for the enzyme, UDP-Galf. Competition STD-NMR titration experiments and
      saturation transfer double difference (STDD) experiments with 2 and 3 were
      undertaken to explore the bifunctionality of this enzyme, in particular to answer
      whether one or two active sites are responsible for the formation of both beta-(1
      ->5)- and beta-(1-->6)-Galf linkages. It was demonstrated that 2 and 3 bind
      competitively at the same site; this suggests that GlfT2 has one active site
      pocket capable of catalyzing both beta-(1-->5) and beta-(1-->6) galactofuranosyl
      transfer reactions. The addition of UDP-Galf to GlfT2 in the presence of either 2
      or 3 generated a tetrasaccharide product; this indicates that the enzyme was
      catalytically active under the conditions at which the STD-NMR experiments were
      carried out.

PMID- 19575372
TI  - Influence of the nucleophile on the Candida antarctica lipase B-catalysed
      resolution of a chiral acyl donor.
AB  - The resolution of methyl (+/-)-3-hydroxypentanoate catalysed by Candida
      antarctica lipase B has been performed by using ammonia and benzyl amine as
      nucleophiles. In all cases, the lipase reacts faster with the R enantiomer of the
      ester, but when benzyl amine is used, the enantiomeric ratio is approximately
      three times as high as that measured for ammonia. The analysis of the molecular
      dynamics simulations carried out over the corresponding deacylation transition
      state analogues indicated specular binding modes between enantiomers that vary
      greatly upon the nucleophile used. For the case of ammonia, an intramolecular
      hydrogen bond between the beta-hydroxyl group and the protons of the nucleophile
      is established. However, the presence of the substituent in benzyl amine disrupts
      this interaction. Instead, the acyl chain binds to a more restrictive area of the
      protein where the higher number of contacts established with the side chains of
      Thr40, Gln157 and Ile189 have been identified as the reason for the higher
      enantioselectivity observed in the aminolysis reaction.

PMID- 19575373
TI  - NMR spectroscopic investigation of early events in IAPP amyloid fibril formation.

PMID- 19575375
TI  - Platinum films with controlled 3-dimensional nanoscopic morphologies and their
      effects on surface enhanced Raman scattering.
AB  - The synthesis of Pt thin films with a controlled nanoscopic architecture that can
      support surface enhanced Raman scattering (SERS) is reported. The syntheses are
      achieved by replicating the pores of a type of mesoporous silica thin film whose
      pore structure could be described as a regular array of vertical channels of
      approximately 9 nm in diameter and their interconnections, forming a 3
      dimensional pore network. Electrochemical deposition into the pores followed by
      the removal of the templates produced Pt films composed of arrays of vertically
      standing Pt nanorods with narrow gaps between them. The 3-dimensional
      nanostructure increases the surface area and enables the Pt film to absorb
      visible light. SERS studies of rhodamine 6G and benzenethiol on such Pt films as
      substrates reveals that the control of the nanostructure is critical for the SERS
      effect.

PMID- 19575374
TI  - A RNA-based approach towards small-molecule inhibitors.

PMID- 19575376
TI  - Synthesis of light-responsive bridged nucleic acid and changes in affinity with
      complementary ssRNA.

PMID- 19575377
TI  - Performance of wide-pore monolithic silica column in protein separation.
AB  - A monolithic wide-pore silica column was newly prepared for protein separation.
      The wide distribution of the pore sizes of monolithic columns was evaluated by
      mercury porosimetry. This column, as well as the conventional monolithic column,
      shows high permeability in the chromatographic separation of low-molecular-sized
      substances. In higher-molecular-sized protein separation, the wide-pore
      monolithic silica column shows better performance than that of the conventional
      monolithic column. Under optimized conditions, five different proteins-
      ribonuclease A, albumin, aldolase, catalase, and ferritin--were baseline
      separated within 3 min, which is faster than that using the particle-packed
      columns. In addition, the monolithic wide-pore silica column could also be
      prepared in fused silica capillary (600 mm long, 0.2 mm i.d.) for highly
      efficient protein separation. The peak capacity of the wide-pore monolithic
      silica capillary column is estimated to be approximately 300 in the case of
      protein separation, which is a characteristic performance.

PMID- 19575378
TI  - Fast analysis of prominent flavonoids in tomato using a monolithic column and
      isocratic HPLC.
AB  - RP HPLC-UV-MS was optimized for simultaneous determination of several prominent
      flavonoids (quercetin, naringenin, naringin, myricetin, rutin and kaempferol)
      using a commercially available monolithic column and isocratic elution. The
      concentration of organic modifier (methanol and ACN) was tested in order to
      obtain the best resolution. The LODs for a UV detector at 254 nm were comprised
      between 0.1 microg/mL for myricetin and quercetin and 0.5 microg/mL for rutin,
      naringin and kaempferol with the precision in the range of 1.5-3.0% RSD. MS
      detection with multiply reaction monitoring (MRM) offers a considerable gain in
      selectivity as well as sensitivity LODs for flavonoids were in the range of 1-20
      ng/mL. The developed method was used for monitoring the content of some
      flavonoids in tomatoes during their maturation process.

PMID- 19575379
TI  - Automated zone-sampling dilution by coupling sequential injection analysis to
      high-throughput HPLC for the direct determination of gemfibrozil.
AB  - A novel automated analytical scheme for the rapid determination of gemfibrozil in
      drug dissolution samples is reported. The procedure is based on direct coupling
      of a low pressure continuous flow technique such as sequential injection analysis
      (SI) to HPLC. SI performs automated dilution of the samples based on zone
      sampling and fills on-line the loop of the high pressure injection valve. Rapid
      separation of the analyte from the samples' matrix can be achieved in less than
      1.0 min, by using a short RP monolithic column (25x4.6 mm id) at a flow rate of 2
      mL/min. The SI and HPLC parts of the setup operate independently: during HPLC
      separation the next sample is treated by SI. This way a maximum throughput of 60
      samples per hour is achieved allowing the complete analysis of a batch of six
      dissolution samples within 12-18 min based on the replicates. The proposed method
      was validated in terms of linearity, LOD and LOQ, precision, selectivity and
      accuracy. Its applicability was tested during quality control of four validation
      batches of a gemfibrozil-containing formulation. The results were in good
      agreement with the HPLC method proposed by the US Pharmacopeia.

PMID- 19575380
TI  - Characterization of monolithic capillary columns using inverse gas
      chromatography.
AB  - Polymeric monoliths of different polymeric natures and different degrees of cross
      linking were prepared in capillaries of inner diameter 100 microm. The properties
      of the monoliths prepared were investigated by means of inverse gas
      chromatography. Solubility coefficient S, Flory-Huggins parameter
      chi(12)(infinity), and reduced Flory-Huggins parameter chi(12)(infinity') were
      evaluated. The solubility parameter S of all samples depends on the degree of
      cross-linking of the monoliths, which is characterized by the reduced Flory
      Huggins parameter chi(12)(infinity'). A linear dependence of the logarithm of the
      solubility parameter S on the solute critical temperature was also demonstrated,
      as it is well known for non-cross linked polymers. The diffusivity of low
      molecular mass solutes in monoliths was evaluated by calculation of the ratio
      D/d(f)(2), and a maximum was detected for the dependence of the ratio D/d(f)(2)
      on the degree of cross-linking of monoliths. Correlation of the measured monolith
      properties with the separation performance of capillary columns was carried out
      and revealed that the best performance in GC is provided by monolithic columns
      prepared from purely bifunctional monomer, i. e. having 100% cross-linking.

PMID- 19575381
TI  - Effect of temperature during photopolymerization of capillary monolithic columns.
AB  - Polymeric monolithic capillary columns were synthesized using butyl methacrylate
      (BMA), ethylene glycol dimethacrylate (EDMA), and 2-acrylamido-2
      methylpropanesulfonic acid (AMPS) as monomers and 1,4-butanediol, 1-propanol, and
      water as a porogen mixture. The synthesis was performed over a wide temperature
      range from -15 degrees C to +70 degrees C using UV radiation to trigger the
      polymerization process initiated by benzoin methyl ether (BME). The columns
      exhibited different hydrodynamic properties (permeability) as well as efficiency.
      The most efficient and the most permeable columns were those polymerized at low
      temperatures (-15 degrees C to +10 degrees C). The columns photopolymerized at
      higher temperatures (T > or = 30 degrees C) were completely useless because of
      low permeability or efficiency. The presented results indicate that temperature
      can be another factor which allows control of porosity during the preparation of
      monoliths by photopolymerization.

PMID- 19575382
TI  - Design and optimization of porous polymer enzymatic digestors for proteomics.
AB  - Effective protein characterization and identification are demanding and time
      consuming operations in proteomics because of long-protein
      purification/separation procedures, and even longer enzymatic digestions. In this
      work, polymer-based monolithic enzyme reactors were fabricated in fused-silica
      capillaries, and performance was characterized through protein digestion and
      identification by MALDI-MS and ESI-MS. Reactors were prepared by fabricating a
      porous methacrylate base monolith followed by photografting with glycidyl
      methacrylate, and immobilization of the enzyme(s) with carbonyldiimidazole.
      Trypsin and Staphylococcus aureus V-8 protease (Glu-C) were used to produce three
      types of reactors: trypsin-based, Glu-C-based, and trypsin combined with Glu-C.
      Protein digestions, performed by perfusing protein solutions through the reactor
      under pressure, were evaluated based on the peptide map generated when directly
      coupled to an ESI mass spectrometer. Excellent digestion was observed over flow
      rates from 0.2 to 1 microL/min, which corresponds to reactor residence times of
      0.24-1.4 min. As a proof of principle, chromatographic separation of model
      proteins followed by the digestion of specific fractions using these proteolytic
      enzyme reactors and ESI-MS is demonstrated.

PMID- 19575383
TI  - Synthesis and structure elucidation of three series of nitro-2-styrylchromones
      using 1D and 2D NMR spectroscopy.
AB  - 2-Styrylchromones, although scarce in nature, constitute a group of oxygen
      heterocyclic compounds which have shown significant biological activities. New
      nitro-2-styrylchromones have been synthesised by the Baker-Venkataraman method,
      and the structure elucidation was accomplished using extensive 1D (1H, 13C) and
      2D NMR spectroscopic studies (COSY, HSQC and HMBC experiments).

PMID- 19575384
TI  - Moral dilemmas film task: A study of spontaneous narratives by individuals with
      autism spectrum conditions.
AB  - People with autism spectrum conditions (ASC) have difficulties with mentalizing,
      empathy, and narrative comprehension. A new test of social and narrative
      cognition, the Moral Dilemmas Film Task, was developed to probe individuals'
      spontaneous understanding of naturalistic film scenes. Twenty-eight individuals
      with ASC and 28 neurotypical controls, matched for age, sex, and IQ, watched four
      short emotionally charged film clips each depicting a moral dilemma, and were
      asked to write about what they had seen. Individuals with ASC produced
      significantly shorter film-based narratives and showed a smaller bias for mental
      states over objects in their narratives than controls. A significant correlation
      was found between verbal IQ and the level of mentalizing in film narratives for
      the ASC group, but not the control group, while the reverse pattern was found
      with a measure of self-reported cognitive and affective empathy. These results
      suggest that to the extent that both groups succeed in viewing moral dilemmas in
      terms of mental content, they do so in different ways, with individuals with ASC
      using verbal scaffolding to increase their ability to draw meaning from social
      scenes. The well-established empathy deficit in ASC extends to spontaneous
      interpretation of moral dilemmas. This new film task has the potential to assay
      different aspects of how the social world is represented differently in ASC,
      including during moral comprehension.

PMID- 19575385
TI  - Mothers, machines, and morals: Harry Harlow's work on primate love from lab to
      legend.

PMID- 19575386
TI  - "Monkeys, babies, idiots" and "primitives": nature-nurture debates and
      philanthropic foundation support for American anthropology in the 1920s and
      1930s.
AB  - There has been a long discussion among historians about the impact that
      foundation policies had on the development of the social sciences during the
      interwar era. This discussion has centered on the degree to which foundation
      officers, particularly from the Rockefeller boards, exercised a hegemonic
      influence on research. In this essay, I argue that the field of American cultural
      anthropology has been neglected and must be reconsidered as a window into
      foundation intervention in nature-nurture debates. Despite foundation efforts to
      craft an anthropology policy that privileged hereditarian explanations, I contend
      that cultural anthropologists were committed to proving the primacy of "nurture,"
      even when that commitment cost them valuable research dollars. It was this
      commitment that provided an essential bulwark for the discipline. Ironically, it
      was the need to negotiate with foundations about the purpose of their research
      that helped cultural anthropologists to articulate their unique, and thus
      intrinsically valuable, approach to nature-nurture debates.

PMID- 19575387
TI  - Separation and divergence: the untold story of James Robertson's and John
      Bowlby's theoretical dispute on mother-child separation.
AB  - The work of Robertson and Bowlby is generally seen as complementary, Robertson
      being the practically oriented observer and Bowlby focusing on theoretical
      explanations for Robertson's observations. The authors add to this picture an
      "untold story" of the collaboration between Robertson and Bowlby: the dispute
      between the two men that arose in the 1960s about the corollaries of separation
      and the ensuing personal animosity. On the basis of unique archival materials,
      this until now little known aspect of the history of attachment theory is
      extensively documented. The deteriorating relationship between Robertson and
      Bowlby is described against the background of different currents in
      psychoanalysis in Britain in the interbellum.

PMID- 19575388
TI  - Organizing intelligence: development of behavioral science and the research based
      model of business education.
AB  - Conventional history of the predominant, research-based model of business
      education (RBM) traces its origins to programs initiated by the Ford Foundation
      after World War II. This paper maps the elite network responsible for developing
      behavioral science and the Ford Foundation agenda. Archival records of the
      actions taken by central nodes in the network permit identification of the
      original vision statement for the model. Analysis also permits tracking progress
      toward realizing that vision over several decades. Behavioral science was married
      to business education from the earliest stages of development. The RBM was a
      fundamental promise made by advocates for social science funding. Appraisals of
      the model and recommendations for reform must address its full history, not the
      partial, distorted view that is the conventional account. Implications of this
      more complete history for business education and for behavioral theory are
      considered.

PMID- 19575390
TI  - Considerations for the control of background fluorescence in clinical flow
      cytometry.
AB  - Accurate measurement of antigen-positive cells by flow cytometry can be hampered
      by background fluorescence of antigen-negative cells and other particles (e.g.,
      debris). This article focuses on three major causes of background
      (autofluorescence, spectral overlap, and undesirable antibody binding) by
      reviewing individual aspects of flow cytometric measurements that contribute to
      these causes. The appropriate use of controls facilitates a thorough
      understanding of these contributing factors as well as the development of robust
      cell labeling protocols intended for routine flow cytometric analysis. We present
      a set of recommendations that enables the user to develop an optimized cell
      labeling protocol that minimizes background and maximizes the ability to reliably
      distinguish between a positive and a negative population of cells. These
      recommendations are also intended to augment existing guidelines designed to aid
      in the formulation of a consensus regarding the utility of flow cytometry for the
      analysis of clinical samples.

PMID- 19575389
TI  - Harmonization of light scatter and fluorescence flow cytometry profiles obtained
      after staining peripheral blood leucocytes for cell surface-only versus
      intracellular antigens with the Fix & Perm reagent.
AB  - Staining for intracellular markers with the Fix & Perm reagent is associated with
      variations in the scatter properties of leucocytes, limiting automated analysis
      of flow cytometry (FCM) data. Here, we investigated those variables significantly
      contributing to changes in the light scatter, autofluorescence, and bcl2 staining
      characteristics of peripheral blood (PB) leucocytes, after fixation with Fix &
      Perm. Our major aim was to evaluate a new mathematical approach for automated
      harmonization of FCM data from datafiles corresponding to aliquots of a sample
      treated with cell-surface-only versus Fix & Perm intracellular staining
      techniques. Overall, neither the anticoagulant used nor sample storage for <24 h
      showed significant impact on the light scatter and fluorescence properties of PB
      leucocytes; similarly, the duration of the fixation period (once >15 min were
      used) had a minimum impact on the FCM properties of PB leucocytes. Conversely,
      changes in cell/protein concentrations and the fixative/sample (vol/vol) ratio
      had a clear impact on the light scatter features of some populations of
      leucocytes. Accordingly, lower cell/protein concentrations were associated with
      lower scatter values, particularly for the neutrophils. Such changes could be
      partially corrected through the use of higher fixative to sample volume ratios.
      Despite the variable changes detected between aliquots of the same sample treated
      with cell surface-only versus intracellular staining procedures, the new
      mathematical approach here proposed and evaluated for automated harmonization of
      common parameters in both datafiles, could correct the FCM profiles of leucocytes
      derived from cells undergoing conventional fixation/permeabilization procedures,
      and made them indistinguishable from those corresponding to aliquots of the same
      sample treated with cell-surface-only staining techniques.

PMID- 19575391
TI  - Adverse effects associated with persistent stimulation of Leydig cells with hCG
      in vitro.
AB  - The detrimental effects of persistent stimulation with hCG were investigated in
      rat Leydig cells in vitro. Significant rise in lipid peroxidation and reactive
      oxygen species (ROS) with concomitant attenuation in the activities of
      antioxidant enzymes: superoxide dismutase, catalase, and glutathione-S
      transferase was observed. Transcripts for catalase and superoxide dismutase were
      also depleted. Subsequent to each hCG challenge, the total antioxidant capacity
      in the target cells also declined significantly (P < 0.05). There was an increase
      in cell apoptosis (23%), which was associated with a rise in caspase-3 activity,
      PARP cleavage, and Fas, FasL, caspase-8 expression. While Bax and Caspase-9
      expression remained unchanged, Bcl-2 demonstrated a marked decline. Taken
      together, the above data indicate that persistent hCG stimulation of Leydig cells
      induced adverse effects leading to oxidative stress and apoptosis which was
      channeled primarily through the extrinsic pathway.

PMID- 19575392
TI  - Current opportunities and challenges in skeletal muscle tissue engineering.
AB  - The purpose of this article is to give a concise review of the current state of
      the art in tissue engineering (TE) of skeletal muscle and the opportunities and
      challenges for future clinical applicability. The endogenous progenitor cells of
      skeletal muscle, i.e. satellite cells, show a high proneness to muscular
      differentiation, in particular exhibiting the same characteristics and function
      as its donor muscle. This suggests that it is important to use an appropriate
      progenitor cell, especially in TE facial muscles, which have a exceptional
      anatomical and fibre composition compared to other skeletal muscle. Muscle TE
      requires an instructive scaffold for structural support and to regulate the
      proliferation and differentiation of muscle progenitor cells. Current literature
      suggests that optimal scaffolding could comprise of a fibrin gel and cultured
      monolayers of muscle satellite cells obtained through the cell sheet technique.
      Tissue-engineered muscle constructs require an adequate connection to the
      vascular system for efficient transport of oxygen, carbon dioxide, nutrients and
      waste products. Finally, functional and clinically applicable muscle constructs
      depend on adequate neuromuscular junctions with neural cells. To reach this, it
      seems important to apply optimal electrical, chemotropic and mechanical
      stimulation during engineering and discover other factors that influence its
      formation. Thus, in addition to approaches for myogenesis, we discuss the current
      status of strategies for angiogenesis and neurogenesis of TE muscle constructs
      and the significance for future clinical use.

PMID- 19575393
TI  - Signalling molecules and growth factors for tissue engineering of cartilage-what
      can we learn from the growth plate?
AB  - Modern tissue engineering concepts integrate cells, scaffolds, signalling
      molecules and growth factors. For the purposes of regenerative medicine, fetal
      development is of great interest because it is widely accepted that regeneration
      recapitulates in part developmental processes. In tissue engineering of cartilage
      the growth plate of the long bone represents an interesting, well-organized
      developmental structure with a spatial distribution of chondrocytes in different
      proliferation and differentiation stages, embedded in a scaffold of extracellular
      matrix components. The proliferation and differentiation of these chondrocytes is
      regulated by various hormonal and paracrine factors. Thus, members of the TGFbeta
      superfamily, the parathyroid hormone-related peptide-Indian hedgehog loop and a
      number of transcription factors, such as Sox and Runx, are involved in the
      regulation of chondrocyte proliferation and differentiation. Furthermore,
      adhesion molecules, homeobox genes, metalloproteinases and prostaglandins play a
      role in the complex regulation mechanisms. The present paper summarizes the
      morphological organization of the growth plate and provides a short but not
      exhaustive overview of the regulation of growth plate development, giving
      interesting insights for tissue engineering of cartilage.

PMID- 19575394
TI  - Porcine EPCs downregulate stem cell markers and upregulate endothelial maturation
      markers during in vitro cultivation.
AB  - In recent years, interest in endothelial progenitor cells (EPCs) in the field of
      tissue engineering and regenerative medicine has increased tremendously. However,
      each clinical stem cell application requires prior validation through animal
      experiments. This study investigates the isolation and characterization of
      porcine EPCs from peripheral blood and the change of their cell surface marker
      expression during in vitro cultivation. RT-PCR demonstrated that the EPCs express
      stem cell markers CD34 and CD133, which decrease with in vitro cultivation time.
      Throughout the cultivation process EPCs did not express monocytic (CD14) or
      haematopoietic marker (CD45). Surprisingly, the CD31 and VE-cadherin expression
      in EPCs was significantly higher than in endothelial cells (ECs). In contrast,
      the VEGFR2 and E-selectin expression was significantly lower than in ECs, but
      increased during the expansion process. This study clarifies the characteristic
      properties of porcine EPCs during cell culture and may help to improve the impact
      of EPC-based therapies in porcine animal studies.

PMID- 19575395
TI  - Electron ionization mass spectrometry of the ryanodine receptor-based Ca(2+)
      channel stabilizer S-107 and its implementation into routine doping control.
AB  - New insights into the biochemistry of cardiac arrhythmia and skeletal muscle
      fatigue have yielded new drug candidates to counteract these phenomena. Major
      biological targets have become ryanodine receptor (RyR)-based Ca(2+)-release
      channels, which tend to 'leak' under various circumstances including strenuous
      exercise and, thus, cause aberrant calcium sparks that entail impaired muscle
      function. Therapeutics, which are referred to as rycals, are currently being
      developed to treat cardiac arrhythmia via enhancement of calstabin-ryanodine
      affinities that causes a stabilization of the RyR. These therapeutics possess
      potential for misuse in sports, and an early implementation of target analytes
      such as the benzothiazepine derivatives S-107 and JTV-519 or putative metabolites
      into doping control screening procedures is recommended. Reference compounds,
      deuterated analogues, and a putative metabolic product were synthesized, and
      electron ionization mass spectra of these products were studied and dissociation
      pathways elucidated by means of tandem mass spectrometry (MS/MS) and accurate
      mass measurements. The characterized analytes were incorporated into existing
      sports drug testing assays based on liquid-liquid extraction and subsequent gas
      chromatography/mass spectrometry (GC/MS) analysis, and specificity, lower limit
      of detection (4-6 ng/mL), intraday and interday precision (1.5-17.2%), as well as
      recovery (63-66%) were determined. The established procedure proved suitable for
      routine doping control analysis to detect a potential misuse of the drug
      candidate S-107 in elite sport.

PMID- 19575397
TI  - 1,8-Bis(dimethylamino)naphthalene: a novel superbasic matrix for matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometric analysis of fatty
      acids.

PMID- 19575398
TI  - An electrospray ionization mass spectrometric study of the interactions between
      crown ethers and tetramethylammonium(-phosphonium) cations.

PMID- 19575399
TI  - Data-dependent electron transfer dissociation of large peptides and medium size
      proteins in a QTOF instrument on a liquid chromatography timescale.
AB  - Liquid chromatography (LC) electron transfer dissociation (ETD) tandem mass
      spectrometry (MS/MS) of protein digests is demonstrated in a hybrid quadrupole
      hexapole orthogonal time-of-flight (OTOF) mass spectrometer. Analyte ions are
      selected in a mass-analyzing quadrupole, accumulated in the hexapole linear ETD
      reaction cell and mutually stored with ETD reagent anions. Product ions are
      collected in an ion cooler and then analyzed by an OTOF mass analyzer. The
      hexapole structure of the ETD reaction cell allows for a broad fragment ion mass
      range distribution and a high ion storage capacity. Analytically useful ETD OTOF
      MS/MS spectra could be obtained at a rate of faster than 2 Hz. When used in
      conjunction with LC this high speed allows for several MS and MS/MS spectra to be
      obtained across each LC peak. An MS scan is used to select the precursor ions.
      With a 1 m flight tube and single reflection, resolutions of about 10 k and a
      mass accuracy of 5 ppm were achieved. When analyzing a 100 fmol solution of a
      tryptic digest of bovine serum albumin (BSA) by LC/ETD MS/MS, 27 unique peptides
      were identified with a summed Mascot score of 1316 using the Swiss Prot database.
      In addition, we explored the capability for analyzing small proteins with the
      present hybrid instrument. ETD MS/MS of intact ubiquitin ([M+12H](12+)) leads to
      the identification of the protein with a Mascot score of 264.

PMID- 19575400
TI  - Suitability of tetrahydofuran as a dopant and the comparison to other existing
      dopants in dopant-assisted atmospheric pressure photoionization mass spectrometry
      in support of drug discovery.
AB  - In this paper, we investigated the suitability of tetrahydofuran (THF) as a
      dopant and compared it against other common dopants for atmospheric pressure
      photoionization mass spectrometry (APPI-MS). In a systematic analysis of 37 drug
      standards and 100 Wyeth proprietary drug candidates, THF was found to increase
      ionization efficiency as high as 33-fold when introduced through a syringe pump
      at a flow rate of 20 microL/min, and as high as 114-fold when introduced through
      the mobile phase at 100 microL/min. As a dopant, THF is as effective as acetone,
      better than anisole, and slightly less effective than toluene for the majority of
      the test compounds. The increase in ionization efficiency by THF was found to be
      compound-dependent. THF was more effective in facilitating the ionization of
      polar compounds than of non-polar compounds. With THF, toluene and acetone as
      dopants, a single type of molecular ion ([M+H](+) or M(+*)) is produced for
      analyte molecules. However, anisole can cause the formation of an ion cluster for
      polar analytes. The cluster contains [M-2H+H](+), M(+*), and [M+H](+) ions with
      varied ratios. This complexity may make interpretation of spectra difficult for
      unknown compounds when complimentary data are not available. Our findings
      indicate that THF is a suitable dopant in the daily usage for increasing
      ionization efficiency, especially when THF is used as the mobile phase or as an
      organic modifier in the mobile phase.

PMID- 19575401
TI  - Muscle and scale isotopic offset of three fish species in the Mediterranean Sea:
      Dentex dentex, Argyrosomus regius and Xyrichtys novacula.
AB  - Diet information of organisms was traditionally acquired by the use of lethal
      techniques (gut content or muscle delta(13)C and delta(15)N isotopic ratios). An
      increase in the number of isotopic ratio studies and the vulnerability of some
      species have led to increased use of non-lethal methodologies for conservation
      purposes. In the present work we have compared the delta(13)C and delta(15)N
      isotopic signals of muscle and scales of three different fish species in order to
      test fish-scale sampling as a non-lethal technique in fish trophodynamics. A
      positive correlation was found between muscle and scales in Argyrosomus regius
      and Xyrichtys novacula, while Dentex dentex showed no correlation due to the
      small length range of this species. The isotopic offset (Delta(13)C and
      Delta(15)N) between muscle and scales was significantly different among species
      (analysis of variance (ANOVA), p < 0.001) with Tukey's post-hoc HSD indicating a
      tissue offset difference (p < 0.001) for both stable isotopes in all species,
      except for Delta(13)C between A. regius and X. novacula and for Delta(15)N
      between D. dentex and X. novacula (p > 0.05). Mean delta(13)C and delta(15)N
      values between species showed significant differences (paired t-test, p < 0.01)
      between muscle and scale with an enrichment for delta(13)C and a depletion for
      delta(15)N. Spatial differences were found in the Delta(13)C of X. novacula
      between the studied locations, while no differences were found for Delta(15)N,
      indicating that non-geographical differences should be considered in the
      application of scales instead of muscle for (15)N, while for (13)C differences in
      the geographical isotopic offset should be considered.

PMID- 19575402
TI  - Electrospray ionisation with selected reaction monitoring for the determination
      of Mn-citrate, Fe-citrate, Cu-citrate and Zn-citrate.
AB  - Citrate complexes of Mn and Fe, and potentially those of Cu and Zn, are
      considered as important low molecular mass species in human serum and
      cerebrospinal fluid (CSF). For example, Mn is supposed to enter the brain under
      excess exposure as Mn-citrate leading to neurotoxic effects. Mn-citrate has been
      characterised in human CSF using chromatography and electrophoresis online with
      inductively coupled plasma mass spectrometry, but not yet with molecular mass
      spectrometry. Therefore, this study explores the potential of electrospray
      ionisation (ESI) with selected reaction monitoring (SRM) for the detection of
      metal-citrate complexes, in particular Mn-citrate. The collision-induced
      dissociation of precursor ions with various metal:citrate stoichiometries was
      studied for Mn-citrate, Fe-citrate, Cu-citrate and Zn-citrate. High selectivity
      was achieved for Mn(II)-citrate even in respect to Fe(III)-citrate which forms
      isobaric precursor ions. The limit of detection for Mn-citrate was estimated to
      be around 250 microg L(-1) (referring to the total Mn content in the standard)
      using flow injection. The sensitivity was sufficient for the determination of Mn
      citrate in standard solutions and in an extract of an Mn-citrate-containing
      supplement. An improved ESI source design is expected to reduce the limits of
      detection significantly. The developed ESI-SRM method has the potential to
      provide complementary data for the quality control of current separation methods
      for metal citrates using element-selective detection, with application to
      biomedical samples and further matrices.

PMID- 19575403
TI  - Energy-resolved depth profiling of metal-polymer interfaces using dynamic
      quadrupole secondary ion mass spectrometry.
AB  - Quadrupole secondary ion mass spectrometry (qSIMS) characterization of a
      metallized polypropylene film used in the manufacturing of capacitors has been
      performed. Ar(+) primary ions were used to preserve the oxidation state of the
      surface. The sample exhibits an incomplete metallization that made it difficult
      to determine the exact location of the metal-polymer interface due to the
      simultaneous contribution of ions with identical m/z values from the metallic and
      the polymer layers. Energy filtering by means of a 45 degrees electrostatic
      analyzer allowed resolution of the metal-polymer interface by selecting a
      suitable kinetic energy corresponding to the ions generated in the metallized
      layer but not from the polymer. Under these conditions, selective analyses of
      isobaric interferences such as (27)Al(+) and (27)C(2)H(3) (+) or (43)AlO(+) and
      (43)C(3)H(7) (+) have been successfully performed.

PMID- 19575404
TI  - Analysing the isotopic life history of the alpine ungulates Capra ibex and
      Rupicapra rupicapra rupicapra through their horns.
AB  - The horn of ungulate grazers offers a valuable isotopic record of their diet and
      environment. However, there have been no reports of the spatio-temporal variation
      of the isotopic composition of horns. We investigated patterns of carbon
      (delta(13)C) and nitrogen (delta(15)N) isotopic composition along and
      perpendicular to the horn axis in Capra ibex and Rupicapra rupicapra rupicapra to
      assess the effects of animal age, within-year (seasonal) and inter-annual
      variation, natural contamination and sampling position on horn isotope
      composition. Horns of male C. ibex (n = 23) and R. r. rupicapra (n = 1) were
      sampled longitudinally on the front (only R. r. rupicapra) and back side and on
      the surface and sub-surface. The sides of the R. r. rupicapra horn did not differ
      in delta(13)C. In both species, the horn surface had a 0.15 per thousand lower
      delta(13)C and a higher carbon-to-nitrogen (C/N) ratio than the sub-surface.
      Washing the horn with water and organic solvents removed material that caused
      these differences. With age, the delta(15)N of C. ibex horns increased (+0.1 per
      thousand year(-1)), C/N ratio increased, and (13)C discrimination relative to
      atmospheric CO(2) ((13)Delta) increased slightly (+0.03 per thousand year(-1)).
      Geostatistical analysis of one C. ibex horn revealed systematic patterns of inter
      annual and seasonal (13)C changes, but (15)N changed only seasonally. The work
      demonstrates that isotopic signals in horns are influenced by natural
      contamination (delta(13)C), age effects ((13)Delta and delta(15)N), and seasonal
      (delta(13)C and delta(15)N) and inter-annual variation (delta(13)C). The methods
      presented allow us to distinguish between these effects and thus allow the use of
      horns as isotopic archives of the ecology of these species and their habitat.

PMID- 19575405
TI  - Oxidation of bovine serum albumin: identification of oxidation products and
      structural modifications.
AB  - Albumin is an important plasma antioxidant protein, contributing to protecting
      mechanisms of cellular and regulatory long-lived proteins. The metal-catalyzed
      oxidation (MCO) of proteins plays an important role during oxidative stress. In
      this study, we examine the oxidative modification of albumin using an MCO in
      vitro system. Mass spectrometry, combined with off-line nano-liquid
      chromatography, was used to identify modifications in amino acid residues. We
      have found 106 different residues oxidatively damaged, being the main oxidized
      residues lysines, cysteines, arginines, prolines, histidines and tyrosines.
      Besides protein hydroxyl derivatives and oxygen additions, we detected other
      modifications such as deamidations, carbamylations and specific amino acid
      oxidative modifications. The oxidative damage preferentially affects particular
      subdomains of the protein at different time-points. Results suggest the oxidative
      damage occurs first in exposed regions near cysteine disulfide bridges with
      residues like methionine, tryptophan, lysine, arginine, tyrosine and proline
      appearing as oxidatively modified. The damage extended afterwards with further
      oxidation of cysteine residues involved in disulfide bridges and other residues
      like histidine, phenylalanine and aspartic acid. The time-course evaluation also
      shows the number of oxidized residues does not increase linearly, suggesting that
      oxidative unfolding of albumin occurs through a step-ladder mechanism.

PMID- 19575406
TI  - A test of comparative equilibration for determining non-exchangeable stable
      hydrogen isotope values in complex organic materials.
AB  - Comparative equilibration has been proposed as a methodological approach for
      determining the hydrogen isotopic composition (deltaD) of non-exchangeable
      hydrogen in complex organic materials, from feathers to blood and soils. This
      method depends on using homogenized standards that have been previously
      calibrated for their deltaD values of non-exchangeable H, that are
      compositionally similar to unknown samples, and that span an appropriate isotopic
      range. Currently no certified organic reference materials with exchangeable H
      exist, and so isotope laboratories have been required to develop provisional
      internal calibration standards, such as the keratin standards currently used in
      animal migration studies. Unfortunately, the isotope ratios of some samples fall
      outside the range of keratin standards currently used for comparative
      equilibration. Here we tested a set of five homogenized keratin powders as well
      as feathers from Painted Buntings and Dark-eyed Juncos to determine the effects
      of extrapolating comparative equilibration normalization equations outside the
      isotopic range of keratin standards. We found that (1) comparative equilibration
      gave precise results within the range of the calibration standards; (2) linear
      extrapolation of normalization equations produced accurate deltaD results to
      approximately 40 per thousand outside the range of the keratins standards used (
      187 to -108); and (3) for both homogenized keratin powders and heterogeneous
      unknown samples there was no difference in variance between samples within and
      outside the range of keratin standards. This suggested that comparative
      equilibration is a robust and practical method for determining the deltaD of
      complex organic matrices, although caution is required for samples that fall far
      outside the calibration range.

PMID- 19575407
TI  - Serum S100B in elderly patients with and without delirium.
AB  - OBJECTIVE: Elevation of S100B has been shown after various neurologic diseases
      with cognitive dysfunction. The aim of this study was to compare the serum level
      of S100B of patients with and without delirium and investigate the possible
      associations with different subtypes of delirium. METHODS: Acutely admitted
      medical patients aged 65 years or more were included from 2005 through 2008.
      Delirium was diagnosed by Confusion Assessment Method, delirium subtype by
      Delirium Symptom Interview and preexistent global cognitive function by the
      'Informant Questionnaire on Cognitive Decline-short form'. S100B levels were
      determined in serum by electrochemiluminescence immunoassay. RESULTS: Samples of
      412 patients were included, 91 during delirium, 35 after delirium and 286 of
      patients without delirium. Patients with delirium (31%) were significantly older,
      81.5 versus 76.6 years (p < 0.001) and experienced significantly more often
      preexistent cognitive and functional impairment (p < 0.001). S100B level differed
      significantly (p = 0.004) between the three groups: median 0.07 microg/L (inter
      quartile ranges: 0.05-0.14 microg/L) during delirium, 0.12 microg/L (0.05-0.29
      microg/L) after delirium and 0.06 microg/L (0.03-0.10 microg/L) in patients
      without delirium. Combining the impact of cognitive impairment, infection and age
      on S100B, highest S100B was observed in the oldest patients after delirium with
      preexistent cognitive impaired and infection. Delirium subtype and S100B level
      were not significantly correlated. CONCLUSION: Higher S100B levels were found in
      patients with delirium than in patients without delirium, with highest levels of
      S100B in samples taken after delirium. Future studies are needed to elucidate the
      mechanism responsible for the increase of S100B and the possible association with
      long term cognitive impairment.

PMID- 19575408
TI  - Searching for in silico predicted metabolites and designer modifications of
      (cortico)steroids in urine by high-resolution liquid chromatography/time-of
      flight mass spectrometry.
AB  - Glucocorticosteroids are a restricted class of substances and appear on the 'in
      competition' prohibited list of the World Anti-Doping Agency (WADA). Analysis of
      glucocorticosteroids is complicated since they show significant phase 1 and 2
      metabolism in the human body and are excreted into urine in concentrations in the
      microg/L range. Full scan, high-resolution time-of-flight mass spectrometry
      analysis generates information on all ionisable components in urine, including
      known and unknown metabolites of steroids and even designer modifications of
      anabolic steroids. However, evaluation of the data obtained can be difficult and
      time-consuming because of the need to differentiate between endogenous components
      and compounds of interest. MetaboLynx, a spectral and chromatographic search
      program, was modified for the determination of in silico predicted metabolites of
      glucocorticosteroids and designer modifications of anabolic steroids in human
      urine. Spiked urine samples were successfully screened for known components in a
      targeted approach and for unknown species in a non-targeted approach using data
      filtering to limit potential false-positives. A simplified combined approach of
      targeted and untargeted screening was used for the detection of metabolites and
      designer modifications of existing compounds. This approach proved successful and
      showed its strength in the detection of tetrahydrogestrinone (THG), a designer
      modification of gestrinone. THG was positively detected in a spiked urine sample
      and correctly identified as a twofold hydrogenation of gestrinone. The developed
      screening method can easily be adapted to specific needs and it is envisaged that
      a similar approach would be amendable to the discovery of metabolites or designer
      modifications of other compounds of interest.

PMID- 19575409
TI  - Low-temperature (9 degrees C) AMD treatment in a sulfidogenic bioreactor
      dominated by a mesophilic Desulfomicrobium species.
AB  - The possibilities for the treatment of low-temperature mine waste waters have not
      been widely studied. The amenability of low-temperature sulfate reduction for
      mine waste water treatment at 9 degrees C was studied in a bench-scale fluidized
      bed bioreactor (FBR). Formate was used as the electron and carbon source. The
      first influent for the FBR was acidic, synthetic waste water containing iron,
      nutrients, and sulfate, followed by diluted barren bioleaching solution (DBBS).
      The average sulfate reduction rates were 8 mmol L(-1) day(-1) and 6 mmol L(-1)
      day(-1) with synthetic waste water and DBBS, respectively. The corresponding
      specific activities were 2.4 and 1.6 mmol SO(4)(2-) g VSS(-1) day(-1),
      respectively. The composition of the microbial community and the active species
      of the FBR was analyzed by extracting the DNA and RNA, followed by PCR-DGGE with
      the universal bacterial 16S rRNA gene primers and dsrB-primers specific for
      sulfate-reducing bacteria. The FBR microbial community was simple and stable and
      the dominant and active species belonged to the genus Desulfomicrobium. In
      summary, long-term operation of a low-temperature bioreactor resulted in
      enrichment of formate-utilizing, psychrotolerant mesophilic sulfate reducing
      bacteria.

PMID- 19575410
TI  - Chondrogenesis on BMP-6 loaded chitosan scaffolds in stationary and dynamic
      cultures.
AB  - We originally investigated the suitability of chitosan scaffolds loaded with bone
      morphogenetic protein 6 (BMP-6) in both stationary and dynamic conditions for
      cartilage tissue engineering. In the first part of the present study, ATDC5
      murine chondrogenic cells were seeded in chitosan and BMP-6 loaded chitosan
      scaffolds and cultured for 28 days under static conditions. In the following
      part, we examined the influence of dynamic cultivation conditions over BMP-6
      loaded chitosan scaffolds by using rotating bioreactor with perfusion (RCMW).
      Tissue engineered constructs were characterized by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-tetrazoliumbromide (MTT) assay, scanning electron microscopy (SEM),
      confocal laser scanning microscopy (CLSM) and biochemical assays for
      glycosaminoglycans (GAG) deoxyribonucleic acid (DNA) and collagen Type II
      quantification. At the end of 4 weeks static incubation period high levels of GAG
      (21.22 mg/g dry weight), DNA amounts (1.37 mg/g dry weight) and collagen Type II
      amounts (1.94 microg/g dry weight) were achieved for BMP-6 loaded chitosan
      scaffolds compared to chitosan scaffolds. However, the results obtained from
      morphological observations suggested hypertrophic differentiation of ATDC5 cells
      in the presence of BMP-6 under stationary conditions. The influence of mechanical
      stimulation appeared significantly with differentiated cells, cultured under
      dynamic conditions, showing the effect of retaining their phenotypes without
      hypertrophy.

PMID- 19575411
TI  - Comparison of inert supports in laser desorption/ionization mass spectrometry of
      peptides: pencil lead, porous silica gel, DIOS-chip and NALDI target.
AB  - In the search for alternative inert surfaces replacing silicon chips in
      Desorption/Ionization On porous Silicon (DIOS)-like mass spectrometry analyses,
      nanostructured silicon-based NALDI chips were evaluated in Laser
      Desorption/Ionization (LDI) of peptides. Comparisons were made using commercially
      available DIOS chips (MassPREP-DIOS-target), amorphous carbon powder from lead
      pencil and porous silica gel used for chromatographic purposes as reference
      supports. A set of synthetic model peptides presenting variable amino acid
      sequences of various lengths was analyzed under all conditions. The LDI responses
      of the four 'matrix-free' techniques were compared, especially in terms of
      peptide detection sensitivity and overall experiment robustness.

PMID- 19575413
TI  - Modification of protein crystal packing by systematic mutations of surface
      residues: implications on biotemplating and crystal porosity.
AB  - Bioinspired nano-scale biotemplating for the development of novel composite
      materials has recently culminated in several demonstrations of nano-structured
      hybrid materials. Protein crystals, routinely prepared for the elucidation of
      protein 3D structures by X-ray crystallography, present an ordered and highly
      accurate 3D array of protein molecules. Inherent to the 3D arrangement of the
      protein "building blocks" in the crystal, a complementary 3D array of
      interconnected cavities--voids array, exhibiting highly ordered porosity is
      formed. The porous arrays of protein crystal may serve as a nano-structured,
      accurate biotemplate by a "filling" process. These cavities arrays are shaped by
      the mode of protein packing throughout the crystallization process. Here we
      propose and demonstrate feasibility of targeting site specific mutations to
      modify protein's surface to affect protein crystal packing, enabling the
      generation of a series of protein crystal "biotemplates" all originating from
      same parent protein. The selection of these modification sites was based on in
      silico analysis of protein-protein interface contact areas in the parent crystal.
      The model protein selected for this study was the N-terminal type II cohesin from
      the cellulosomal scaffold in ScaB subunit of Acetivibrio cellulolyticus and
      mutations were focused on lysine residues involved in protein packing as prime
      target. The impact of systematically mutating these lysine residues on protein
      packing and its resulting interconnected cavities array were found to be most
      significant when surface lysine residues were substituted to tryptophan residues.
      Our results demonstrate the feasibility of using pre-designed site directed
      mutations for the generation of a series of protein crystal biotemplates from a
      "parent" protein.

PMID- 19575412
TI  - fMRI activation in late-life anxious depression: a potential biomarker.
AB  - OBJECTIVE AND METHODS: The neurobiology of late-life anxious depression (LLAD) is
      poorly characterized despite evidence that this is a common and severe subtype of
      late-life depression. To identify the neuroanatomical substrate of LLAD, we
      examined event-related fMRI data collected in eight subjects with late-life
      depression, half of whom had high levels of comorbid anxiety. Subjects were
      trained on the Preparing to Overcome Prepotency (POP) task, which is an executive
      control task that reliably activates the lateral prefrontal cortex-anterior
      cingulate cortex (ACC) cognitive control circuit. RESULTS: Time series analysis
      showed that, when compared with elderly depressed subjects, elderly subjects with
      anxious depression performing the POP task produced a significantly greater and
      more sustained signal in three regions: BA24 (dorsal anterior cingulate), BA31
      (posterior cingulate), and BA6 (prefrontal cortex). While elderly subjects with
      pure depression presented a bimodal activation curve in the dorsal anterior
      cingulate and the posterior cingulate, elderly subjects with anxious depression
      presented a sustained unimodal activation pattern. CONCLUSIONS: Our preliminary
      results suggest specific activation patterns unique to anxious depression that
      may suggest greater and more sustained efforts of the ACC to carry out cognitive
      control tasks. Further research is needed to clarify the neuroanatomical basis of
      LLAD.

PMID- 19575414
TI  - Understanding the mechanism of virus removal by Q sepharose fast flow
      chromatography during the purification of CHO-cell derived biotherapeutics.
AB  - During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell
      culture, it is important to ensure that viral impurities and potential viral
      contaminants will be removed during downstream purification. Anion exchange
      chromatography provides a high degree of virus removal from mAb feedstocks, but
      the mechanism by which this is achieved has not been characterized. In this work,
      we have investigated the binding of three viruses to Q sepharose fast flow (QSFF)
      resin to determine the degree to which electrostatic interactions are responsible
      for viral clearance by this process. We first used a chromatofocusing technique
      to determine the isoelectric points of the viruses and established that they are
      negatively charged under standard QSFF conditions. We then determined that virus
      removal by this chromatography resin is strongly disrupted by the presence of
      high salt concentrations or by the absence of the positively charged Q ligand,
      indicating that binding of the virus to the resin is primarily due to
      electrostatic forces, and that any non-electrostatic interactions which may be
      present are not sufficient to provide virus removal. Finally, we determined the
      binding profile of a virus in a QSFF column after a viral clearance process.
      These data indicate that virus particles generally behave similarly to proteins,
      but they also illustrate the high degree of performance necessary to achieve
      several logs of virus reduction. Overall, this mechanistic understanding of an
      important viral clearance process provides the foundation for the development of
      science-based process validation strategies to ensure viral safety of
      biotechnology products.

PMID- 19575415
TI  - Evaluation of monoclonal antibody and phenolic extraction from transgenic Lemna
      for purification process development.
AB  - Several pharmaceutical protein products made in transgenic plant hosts are
      advancing through clinical trials. Plant hosts present a different set of
      impurities from which the proteins must be purified compared to other expression
      hosts such as mammalian cells. In this work, phenolic compounds present in
      extracts of monoclonal antibody (mAb)-expressing Lemna minor were examined. Two
      different extraction pHs were evaluated to assess the effect of extraction
      condition on the concentration of mAb and phenolics in the extracts. The extract
      prepared at pH 4.5 had an enriched level of mAb relative to native protein when
      compared to a pH 7.5 extract although similar overall mAb was extracted at either
      pH. Slightly more mAb was recovered from the pH 3 elution of the pH 4.5 extract
      run on a MabSelect column than was recovered from the pH 7.5 extract. Phenolic
      levels in extracts were assessed by spectrophotometry, Folin-Ciocalteu assay and
      by profiling on RP-HPLC. The Folin-Ciocalteu assay results did not agree with
      those obtained by the other two methods. Therefore phenolic levels were
      quantified by RP-HPLC comparing the total area of phenolic peaks to those of
      reference phenolic compounds. The pH 7.5 extract had 22% less phenolics than the
      pH 4.5 extract. Acidic precipitation of the pH 7.5 extract resulted in further
      reduction of phenolics originally present in the pH 7.5 extract. The total
      phenolics present in the extracts were effectively removed by incubation of
      extracts with a commercially available anion exchange resin, Amberlite IRA-402.
      We anticipate that early removal of phenolic compounds will prolong the life of
      more expensive affinity columns used for the purification of potential
      pharmaceutical proteins and should therefore be considered in process development
      involving proteins extracted from transgenic plant hosts.

PMID- 19575416
TI  - Development and evaluation of efficient recombinant Escherichia coli strains for
      the production of 3-hydroxypropionic acid from glycerol.
AB  - 3-Hydroxypropionic acid (3-HP) is a commercially valuable chemical with the
      potential to be a key building block for deriving many industrially important
      chemicals. However, its biological production has not been well documented. Our
      previous study demonstrated the feasibility of producing 3-HP from glycerol using
      the recombinant Escherichia coli SH254 expressing glycerol dehydratase (DhaB) and
      aldehyde dehydrogenase (AldH), and reported that an "imbalance between the two
      enzymes" and the "instability of the first enzyme DhaB" were the major factors
      limiting 3-HP production. In this study, the efficiency of the recombinant
      strain(s) was improved by expressing DhaB and AldH in two compatible isopropyl
      thio-beta-galactoside (IPTG) inducible plasmids along with glycerol dehydratase
      reactivase (GDR). The expression levels of the two proteins were measured. It was
      found that the changes in protein expression were associated with their enzymatic
      activity and balance. While cloning an alternate aldehyde dehydrogenase (ALDH),
      alpha-ketoglutaric semialdehyde dehydrogenase (KGSADH), instead of AldH, the
      recombinant E. coli SH-BGK1 showed the highest level of 3-HP production (2.8 g/L)
      under shake-flask conditions. When an aerobic fed-batch process was carried out
      under bioreactor conditions at pH 7.0, the recombinant SH-BGK1 produced 38.7 g 3
      HP/L with an average yield of 35%. This article reports the highest level of 3-HP
      production from glycerol thus far.

PMID- 19575417
TI  - Glioblastoma targeting via integrins is concentration dependent.
AB  - A novel approach to treat cancer more selectively is achieved by targeting drugs
      to cells via conjugating the drug or imaging agent to an antibody or ligand for a
      cell surface receptor that is over-expressed by the target cell population.
      Previous work by us has suggested that enhanced specificity can be obtained by
      multivalency of binding moieties. In this study we investigated the binding
      specificity of a multivalent construct including three peptides segments
      (TWYKIAFQRNRK), which bind the alpha(6)beta(1)-integrin, linked by poly(ethylene
      glycol) spacers. The binding specificity of the constructs was calculated by
      quantifying their binding to target cells (glioma cells, SF 767) relative to non
      targeted cells (normal human astrocytes, NHA). Dodecapeptide constructs
      (monovalent) exhibit specificity equal to the ratio of receptor expression at all
      concentrations. However, trivalent constructs demonstrated a sharp increase in
      specificity at concentrations less than the affinity of the receptor-ligand bond
      (4.28 microM). These experiments (conducted at 4 degrees C) were consistent with
      the theoretical prediction and indicate that the biophysical model captures the
      basic trend of the data in the absence of receptor internalization, although the
      concentration at which increased specificity is observed is greater than
      predicted. The biophysical model does not predict the results of 37 degrees C
      experiments, and this is shown to be due to internalization which occurs at 37
      degrees C but not at 4 degrees C.

PMID- 19575418
TI  - Investigation of multifocal choroiditis with panuveitis by three-dimensional high
      penetration optical coherence tomography.
AB  - A single case of multifocal choroiditis with panuveitis (MFCPU) was investigated
      by a three-dimensional (3-D) high-penetration optical coherence tomography. The
      HP-OCT is based on a swept-source OCT technology, uses a probe beam with a center
      wavelength of 1060 nm, and possesses a depth resolution of 10.4 micromin tissue.
      Two eyes of an MFCPU patient were involved in this study. The eyes were also
      examined by color fundus photograph, fluorescein angiography (FA), and
      indocyanine green angiography (ICGA). Findings in these four modalities are
      comparatively discussed. The OCT scans revealed the following characteristic
      properties of the lesion sites. Thinning of the retina, destructuring of the
      retinal layers, and disappearance of the junction of the inner and outer segments
      of the photoreceptor (IS/OS). Due to the high penetration of this OCT system, the
      following characteristic properties of the lesions were also observed: localized
      thinning of the choroid, occlusion of the choroidal vessels, and localized hyper
      reflectivity that may represent hyper-pigmentation of the choroid.

PMID- 19575419
TI  - The cognitive change checklist (3CL): cross-validation of a measure of change in
      everyday cognition.
AB  - OBJECTIVE: The recently developed cognitive change checklist (3CL) is comprised
      of four scales titled memory, executive, language, and remote recall. A previous
      study demonstrated that the checklist met criteria for reliability and validity
      in characterizing cases of mild cognitive impairment (MCI) and early dementia in
      a memory disorder clinic sample. In this study we examined further the
      reliability, validity, and efficacy of the 3CL in distinguishing among groups of
      normal individuals, those with cognitive complaints, amnestic and non-amnestic
      MCI cases, and early-stage demented individuals. DESIGN: Scale validation study.
      SETTING: Alzheimer's Disease Research Center PARTICIPANTS: One hundred and twenty
      five individuals who completed extensive evaluations as part of a longitudinal
      study of cognitive change. RESULTS: Scale reliabilities were found to be well
      within guidelines to support their use in the clinical assessment of change in
      global and specific cognitive domains. The factor structure of the 3CL was found
      to be highly similar to that originally reported. Validation support was obtained
      from correlational analyses that showed significant scale relationships with
      neurocognitive measures and with MRI ratings of medial temporal atrophy.
      Informant 3CL scales were found to discriminate individuals with cognitive
      complaints but without clinical findings from those individuals with amnestic MCI
      or early dementia. CONCLUSION: Results extend the foundation of support for the
      use of the 3CL as a measure to facilitate identification of cases of MCI and
      early AD. Further examination of the diagnostic utility of the scale, and of its
      value in combination with cognitive screening measures, will also be required.

PMID- 19575420
TI  - Docetaxel down-regulates the expression of androgen receptor and prostate
      specific antigen but not prostate-specific membrane antigen in prostate cancer
      cell lines: implications for PSA surrogacy.
AB  - BACKGROUND: Docetaxel (DOC) has potent anti-tumor efficacy as a result of
      promoting microtubule assembly and microtubule bundling thereby impairing
      mitosis. Knowing that some anti-microtubule agents affect the polarity of
      prostate-specific membrane antigen (PSMA) expression and that androgen ablation
      can up-regulate PSMA expression, we sought to determine any effect of DOC on PSMA
      expression in prostate cancer (PC) cell lines as a prelude to a clinical effort.
      As controls, we also looked at the expression of androgen receptor (AR) and
      prostate-specific antigen (PSA). METHODS: The effect of DOC on cell viability and
      PSMA, AR, and PSA expression was examined by flow cytometry and immunoblotting
      using LNCaP, CWR22Rv1, and MDA-PCa-2b cells. The effect of DOC on PSA levels of
      LNCaP and MDA-PCa-2b cells was also measured in conditioned media. The effect of
      DOC was also studied using LNCaP and MDA-PCa-2b cells that were transfected to
      over-express AR. RESULTS: PSMA levels were not affected by DOC treatment.
      Unexpectedly, we found DOC significantly down-regulated both AR and PSA in a dose
      dependent manner in the cell lines studied. Over-expression of AR partially
      abrogated the cytotoxic effects of DOC. CONCLUSIONS: While DOC did not affect
      PSMA expression, it was unexpectedly found to down-regulate AR and PSA. DOC
      induced down-regulation of AR might be one of the anti-tumor mechanisms active in
      PC. Down-regulation of PSA may account for the significantly higher PSA response
      rates (45-50%) relative to measurable response rates (8-17%) reported in DOC PC
      trials and have implications for PSA surrogacy observations derived from DOC
      trials.

PMID- 19575421
TI  - Desipramine inhibits the growth of a mouse skin squamous cell carcinoma cell line
      and affects glucocorticoid receptor-mediated transcription.
AB  - The purpose of this study was to examine the effect of tricyclic antidepressant
      desipramine (DMI) on the growth inhibition and translocation of the
      glucocorticoid receptor (GR) from the cytoplasm to the nucleus in cancerous and
      noncancerous cell lines and the effect of DMI on GR-mediated transcription.
      Nontumorigenic, immortalized keratinocytes cell line (3PC), papilloma (MT1/2),
      and squamous cell carcinoma (Ca3/7) cell lines were initially used to study the
      cell growth inhibition by DMI. Although, the growth of all three cell lines was
      suppressed by DMI, it was more effective in Ca3/7 cells. Therefore, we next
      examined the effect of DMI on Ca3/7 cells, resistant to growth inhibition by the
      synthetic glucocorticoid fluocinolone acetonide (FA). DMI inhibited cell
      proliferation in a time-dependent manner. The translocation of GR was induced by
      FA alone, DMI alone, and combination of both agents. FA induced GR-mediated
      transcription in Ca3/7 cells transfected with a luciferase reporter gene under
      the control of glucocorticoid response element (GRE), but DMI alone did not
      affect GR-mediated transcription. However, DMI inhibited FA-induced, GR-mediated
      transcription when both agents were given together. Pretreatment with DMI
      followed by combination of DMI and FA decreased GR-mediated transcription more
      than pretreatment with FA. The expression of metallothionein-1 (Mt-1) gene, which
      is regulated by GR, was induced significantly by the combination of DMI and FA,
      and enhanced significantly by pretreatment with FA but not DMI. DMI is suggested
      to inhibit the growth of Ca3/7 cells and to affect GR-mediated transcription.

PMID- 19575423
TI  - Hybrid polymerization of vinyl and hetero-ring groups of glycidyl methacrylate
      resulting in thermoresponsive hyperbranched polymers displaying a wide range of
      lower critical solution temperatures.
AB  - Hybrid polymerization of glycidyl methacrylate (GMA) with potassium hydride (KH)
      and various oligo(ethylene glycol)s as the initiating system, in which both vinyl
      polymerization and ring-opening polymerization occur simultaneously, generates
      hyperbranched poly(ether-ester)s. The reaction process has been followed by an in
      situ nuclear magnetic resonance technique. The experimental results indicate that
      both the vinyl and epoxy groups of GMA undergo polymerization, with the
      reactivity of the latter being much higher than that of the former.
      Interestingly, the resulting hyperbranched polymers exhibit a sharp phase
      transition in water at the lower critical solution temperature (LCST).
      Significantly, the LCST values can be accurately controlled from 0 to 100 degrees
      C by changing the hydrophilic/hydrophobic balance of GMA and various
      oligo(ethylene glycol)s or by modification of the precursor polymer through
      acetylation. This novel stimuli-responsive hyperbranched polymer is a promising
      candidate for a new generation of commercially viable thermoresponsive polymers
      following on from the widely used poly(N-isopropylacrylamide) (PNIPAM).

PMID- 19575424
TI  - Mechanisms in the reaction of palladium(II)-pi-allyl complexes with aryl halides:
      evidence for NHC exchange between two palladium complexes.
AB  - A detailed experimental and DFT study (PBE level) of the reaction of [Pd(eta(3)
      C(3)H(5))(tmiy)(PR(3))]BF(4) (tmiy = tetramethylimidazolin-2-ylidene, PR(3) =
      phosphane), precursors to monoligated Pd(0) species, with aryl electrophiles
      yielding 2-arylimidazolium salt is reported. Experiments establish that an
      autocatalytic ligand transfer mechanism is preferred over Pd(IV) and sigma-bond
      metathesis pathways, and that transmetalation is the rate-determining step.
      Calculations indicate that the key step involves the concerted exchange of NHC
      and iodo ligands between two different Pd(II) complexes. This is corroborated by
      experimental results showing the slower reaction of complexes containing the
      bulkier dipdmiy (dipdmiy = diisopropyldimethylimidazolin-2-ylidene).

PMID- 19575422
TI  - Mature adult dystrophic mouse muscle environment does not impede efficient
      engrafted satellite cell regeneration and self-renewal.
AB  - Changes that occur in the skeletal muscle environment with the progress of
      muscular dystrophies may affect stem cell function and result in impaired muscle
      regeneration. It has previously been suggested that the success of stem cell
      transplantation could therefore be dependent both on the properties of the cell
      itself and on the host muscle environment. Here we engrafted young and mature
      adult mdx-nude mice, which are the genetic homolog of Duchenne muscular
      dystrophy, with a small number of satellite cells freshly isolated from young,
      normal donor mice. We found that the donor satellite cells contributed to muscle
      regeneration and self-renewal as efficiently within mature adult, as in young,
      dystrophic host muscle. Donor-derived satellite cells also contributed to robust
      regeneration after further injury, showing that they were functional despite the
      more advanced dystrophic muscle environment. These findings provide evidence that
      muscle tissue in a later stage of dystrophy may be effectively treated by stem
      cells.

PMID- 19575425
TI  - A cascade FRET-mediated ratiometric sensor for Cu2+ ions based on dual
      fluorescent ligand-coated polymer nanoparticles.
AB  - Core-shell type dual fluorescent nanoparticles (NPs) in the 16 nm diameter range
      with a selective ligand (cyclam) attached to the surface and two fluorophores-
      9,10-diphenyl-anthracene (donor, D) and pyrromethene PM 567 (acceptor, A)-
      embedded within the polymer core were synthesized and their fluorescent and
      copper-sensing properties were studied and compared to single D-doped and A-doped
      NPs. The acceptor (A) and donor (D) dyes were chosen to allow two sequential
      Forster resonance energy transfer (FRET) processes from D to A and from the
      encapsulated dyes to copper complexes that form at the surface and act as
      quenchers. NPs with different D/A loads were readily obtained by two consecutive
      entrapments of the dyes. Dual NPs present tunable fluorescence emission that is
      dependent on the doping ratio. FRET from D to A results in sensitized emission
      from A upon excitation of D, with FRET efficiencies reaching 80 % at high
      acceptor loads. A 9-fold amplification of the signal of A is observed at high D
      to-A ratios. Single- and dual-dye-doped NPs were used to detect the presence of
      cupric ions in water by using the quenching of fluorescence as a transduction
      signal. In accordance with the spectral overlaps and the values of the critical
      distance (R0) of D- and A-copper complex pairs, the acceptor is much more
      sensitive than the donor. In dual fluorescent NPs, the sensitized emission of A
      is efficiently attenuated whereas the remaining emission of D is much less
      affected, allowing the detection of copper in a ratiometric manner upon
      excitation at a single (D) wavelength. Dual-dye-doped NPs with the highest
      acceptor loads (23 A-per-NP) were found to be the most sensitive for the
      detection of copper over a wide range of concentrations (20 nM to 8.5 microM).
      Owing to its great convenience and modularity, the cascade FRET strategy based on
      dual fluorescent NPs holds great promise for the design of various sensing
      nanodevices.

PMID- 19575426
TI  - Stereospecific synthesis of beta3-amino acid derivatives from propargylic
      alcohols: efficient solution-phase synthesis of oligopeptides without coupling
      agents.
AB  - A stereospecific synthesis of beta(3)-amino acids has been accomplished starting
      from readily available and enantioenriched propargylic alcohols. This conversion
      can be effected in only three steps by selenium-mediated organic transformations
      of the carbon-carbon triple bond. This method is especially attractive because
      the reactive Se-phenyl selenocarboxylate intermediates can be trapped with the
      amine functionality of an amino acid derivative. Through this strategy a chain
      elongation at the N-terminus has been effected. The N-deprotection and repetition
      of the homologation with other Se-phenyl selenocarboxylate intermediates produced
      beta- and mixed alpha/beta-oligopeptides without the use of coupling agents.

PMID- 19575427
TI  - A complete multiscale modelling approach for polymer-clay nanocomposites.
AB  - We present an innovative, multiscale computational approach to probe the
      behaviour of polymer-clay nanocomposites (PCNs). Our modeling recipe is based on
      1) quantum/force-field-based atomistic simulation to derive interaction energies
      among all system components; 2) mapping of these values onto mesoscopic bead
      field (MBF) hybrid-method parameters; 3) mesoscopic simulations to determine
      system density distributions and morphologies (i.e., intercalated versus
      exfoliated); and 4) simulations at finite-element levels to calculate the
      relative macroscopic properties. The entire computational procedure has been
      applied to two well-known PCN systems, namely Nylon 6/Cloisite 20A and Nylon
      6/Cloisite 30B, as test materials, and their mechanical properties were predicted
      in excellent agreement with the available experimental data. Importantly, our
      methodology is a truly bottom-up approach, and no "learning from experiment" was
      needed in any step of the entire procedure.

PMID- 19575428
TI  - Can you cover me now?

PMID- 19575429
TI  - Electrochemically induced intermolecular anion transfer.

PMID- 19575430
TI  - Electrochemical properties of a disilene, a tetrasila-1,3-butadiene, and their
      germanium analogues.
AB  - The redox properties of aryl-substituted disilene (1), tetrasila-1,3-butadiene
      (2), digermene (3), and tetragerma-1,3-butadiene (4) (in which the aryl group is
      2,4,6-triisopropylphenyl) have been studied by cyclic voltammetry (CV) in two
      different solvents. In o-dichlorobenzene, disilene 1 exhibited reversible redox
      couples in both oxidation and reduction processes, whereas tetrasilabutadiene 2
      showed a reversible behavior only in its oxidation and an irreversible wave in
      its reduction. Tetragermabutadiene 4 afforded a reversible couple in its
      reduction and an irreversible wave in its oxidation, whereas digermene 3 showed
      only an irreversible oxidation wave but no reduction one. In comparison, all
      observed oxidation and reduction waves in THF were irreversible. In both
      solvents, the same trend of decreasing ease of oxidation has been observed:
      2>4>3>1. The calculated vertical ionization energies (E(i)) for the 2,6
      dimethylphenyl-substituted model compounds 9-12 afforded a trend of ease of
      oxidation that decreases in the series tetrasilabutadiene 10>tetragermabutadiene
      12>disilene 9>digermene 11. This predicted trend parallels the measured oxidation
      potentials in the sense that the heavy butadienes are easier to oxidize than the
      heavy alkenes. The trend in the reduction direction has been found to be
      different in the two solvents studied. The computed electron affinities (E(ea))
      for compounds 9-12 indicated that the ease of reduction decreased in the sequence
      tetragermabutadiene 12>tetrasilabutadiene 10>digermene 11>disilene 9. However, no
      straightforward relation between the computed electron affinities and the
      experimentally measured reduction potentials has been found.

PMID- 19575431
TI  - Enzyme-responsive controlled release using mesoporous silica supports capped with
      lactose.

PMID- 19575432
TI  - Functionalized chitosan as a green, recyclable, biopolymer-supported catalyst for
      the [3+2] Huisgen cycloaddition.

PMID- 19575433
TI  - Fe3O4 core/layered double hydroxide shell nanocomposite: versatile magnetic
      matrix for anionic functional materials.

PMID- 19575434
TI  - Synthesis of the monomeric unit of the lomaiviticin aglycon.

PMID- 19575435
TI  - Characterization of electrochemical activity of a strain ISO2-3 phylogenetically
      related to Aeromonas sp. isolated from a glucose-fed microbial fuel cell.
AB  - The microbial communities associated with electrodes in closed and open circuit
      microbial fuel cells (MFCs) fed with glucose were analyzed by 16S rRNA approach
      and compared. The comparison revealed that bacteria affiliated with the Aeromonas
      sp. within the Gammaproteobacteria constituted the major population in the closed
      circuit MFC (harvesting electricity) and considered to play important roles in
      current generation. We, therefore, attempted to isolate the dominant bacteria
      from the anode biofilm, successfully isolated a Fe (III)-reducing bacterium
      phylogenetically related to Aeromonas sp. and designated as strain ISO2-3. The
      isolated strain ISO2-3 could grow and concomitantly produce current (max. 0.24
      A/m(2)) via oxidation of glucose or hydrogen with an electrode serving as the
      sole electron acceptor. The strain could ferment glucose, but generate less
      electrical current. Cyclic voltammetry supported the strain ISO2-3 was
      electrically active and likely to transfer electrons to the electrode though
      membrane-associated compounds (most likely c-type cytochrome). This mechanism
      requires intimate contact with the anode surface. Scanning electron microscopy
      revealed that the strain ISO2-3 developed multiplayer biofilms on the anode
      surface and also produced anchor-like filamentous appendages (most likely pili)
      that may promote long-range electron transport across the thick biofilm.

PMID- 19575436
TI  - Expression of merA, trxA, amoA, and hao in continuously cultured Nitrosomonas
      europaea cells exposed to cadmium sulfate additions.
AB  - The effects of CdSO(4) additions on the gene expressions of a mercury reductase,
      merA, an oxidative stress protein, trxA, the ammonia-monooxygenase enzyme (AMO),
      amoA, and the hydroxylamine oxidoreductase enzyme (HAO), hao, were examined in
      continuously cultured N. europaea cells. The reactor was fed 50 mM NH(4)+ and was
      operated for 78 days with a 6.9 days hydraulic retention time. Over this period,
      six successive batch additions of CdSO(4) were made with increasing maximum
      concentrations ranging from 1 to 60 microM Cd(2+). The expression of merA was
      highly correlated with the level of Cd(2+) within the reactor (Rs = 0.90) with
      significant up-regulation measured at non-inhibitory Cd(2+) concentrations.
      Cd(2+) appears to target AMO specifically at lower concentrations and caused
      oxidative stress at higher concentrations, as indicated by the SOURs (specific
      oxygen uptake rates) and the up-regulation of trxA. Since Cd(2+) inhibition is
      irreversible and amoA was up-regulated in response to Cd(2+) inhibition, it is
      hypothesized that de novo synthesis of the AMO enzyme occurred and was
      responsible for the observed recovery in activity. Continuously cultured N.
      europaea cells were more resistant to Cd(2+) inhibition than previously examined
      batch cultured cells due to the presence of Mg(2+) and Ca(2+) in the growth
      media, suggesting that Cd(2+) enters the cell through Mg(2+) and Ca(2+) import
      channels. The up-regulation of merA during exposure to non-inhibitory Cd(2+)
      levels indicates that merA is an excellent early warning signal for Cd(2+)
      inhibition.

PMID- 19575437
TI  - Construction of Hansenula polymorpha strains with improved thermotolerance.
AB  - The methylotrophic yeast Hansenula polymorpha has the potential to be used in the
      process of simultaneous saccharification and fermentation (SSF) of xylan derived
      xylose at elevated temperatures. To improve parameters of high-temperature
      resistance and high-temperature fermentation of H. polymorpha, strains carrying
      deletion of acid trehalase gene (ATH1) and overexpressing genes coding for heat
      shock proteins Hsp16p and Hsp104p were constructed. Results indicate that the
      corresponding recombinant strains have up to 12-fold increased tolerance to heat
      shock treatment. The deletion of ATH1 gene and constitutive expression of HSP16
      and HSP104 resulted in up to 5.8-fold improvement of ethanol production from
      xylose at 50 degrees C. Although the maximum ethanol concentration achieved from
      xylose was 0.9 g L(-1), our model H. polymorpha strains with elevated
      thermotolerance can be further modified by metabolic engineering to construct
      improved high-temperature ethanol producers from this pentose.

PMID- 19575438
TI  - Bacterial artificial chromosome library for genome-wide analysis of Chinese
      hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cell lines are widely used for scientific research
      and biotechnology. A CHO genomic bacterial artificial chromosome (BAC) library
      was constructed from a mouse dihydrofolate reductase (DHFR) gene-amplified CHO
      DR1000L-4N cell line for genome-wide analysis of CHO cell lines. The CHO BAC
      library consisted of 122,281 clones and was expected to cover the entire CHO
      genome five times. A CHO chromosomal map was constructed by fluorescence in situ
      hybridization (FISH) imaging using BAC clones as hybridization probes (BAC-FISH).
      Thirteen BAC-FISH marker clones were necessary to identify all the 20 individual
      chromosomes in a DHFR-deficient CHO DG44 cell line because of the aneuploidy of
      the cell line. To determine the genomic structure of the exogenous Dhfr amplicon,
      a 165-kb DNA region containing exogenous Dhfr was cloned from the BAC library
      using high-density replica (HDR) filters and Southern blot analysis. The
      nucleotide sequence analysis revealed a novel genomic structure in which the
      vector sequence containing Dhfr was sandwiched by long inverted sequences of the
      CHO genome.

PMID- 19575439
TI  - Simultaneous saccharification and co-fermentation of paper sludge to ethanol by
      Saccharomyces cerevisiae RWB222--Part I: kinetic modeling and parameters.
AB  - A kinetic model was developed to predict batch simultaneous saccharification and
      co-fermentation (SSCF) of paper sludge by the xylose-utilizing yeast
      Saccharomyces cerevisiae RWB222 and the commercial cellulase preparation Spezyme
      CP. The model accounts for cellulose and xylan enzymatic hydrolysis and
      competitive uptake of glucose and xylose. Experimental results show that glucan
      and xylan enzymatic hydrolysis are highly correlated, and that the low
      concentrations of xylose encountered during SSCF do not have a significant
      inhibitory effect on enzymatic hydrolysis. Ethanol is found to not only inhibit
      the specific growth rate, but also to accelerate cell death. Glucose and xylose
      uptake rates were found to be competitively inhibitory, but this did not have a
      large impact during SSCF because the sugar concentrations are low. The model was
      used to evaluate which constants had the greatest impact on ethanol titer for a
      fixed substrate loading, enzyme loading, and fermentation time. The cellulose
      adsorption capacity and cellulose hydrolysis rate constants were found to have
      the greatest impact among enzymatic hydrolysis related constants, and ethanol
      yield and maximum ethanol tolerance had the greatest impact among fermentation
      related constants.

PMID- 19575440
TI  - Simultaneous saccharification and co-fermentation of paper sludge to ethanol by
      Saccharomyces cerevisiae RWB222. Part II: investigation of discrepancies between
      predicted and observed performance at high solids concentration.
AB  - The simultaneous saccharification and co-fermentation (SSCF) kinetic model
      described in the companion paper can predict batch and fed batch fermentations
      well at solids concentrations up to 62.4 g/L cellulose paper sludge but not in
      batch fermentation at 82.0 g/L cellulose paper sludge. Four hypotheses for the
      discrepancy between observation and model prediction at high solids concentration
      were examined: ethanol inhibition, enzyme deactivation, inhibition by non
      metabolizable compounds present in paper sludge, and mass transfer limitation.
      The results show that mass transfer limitation was responsible for the
      discrepancy between model and experimental data. The model can predict the value
      of high paper sludge SSCF in the fermentation period with no mass transfer
      limitation. The model predicted that maximum ethanol production of fed-batch
      fermentation was achieved when it was run as close to batch mode as possible with
      the initial solids loading below the mass transfer limitation threshold. A method
      for measuring final enzyme activity at the end of fermentation was also developed
      in this study.

PMID- 19575441
TI  - Photosynthetic microbial fuel cells with positive light response.
AB  - The current study introduces an aerobic single-chamber photosynthetic microbial
      fuel cell (PMFC). Evaluation of PMFC performance using naturally growing fresh
      water photosynthetic biofilm revealed a weak positive light response, that is, an
      increase in cell voltage upon illumination. When the PMFC anodes were coated with
      electrically conductive polymers, the rate of voltage increased and the amplitude
      of the light response improved significantly. The rapid immediate positive
      response to light was consistent with a mechanism postulating that the
      photosynthetic electron-transfer chain is the source of the electrons harvested
      on the anode surface. This mechanism is fundamentally different from the one
      exploited in previously designed anaerobic microbial fuel cells (MFCs), sediment
      MFCs, or anaerobic PMFCs, where the electrons are derived from the respiratory
      electron-transfer chain. The power densities produced in PMFCs were substantially
      lower than those that are currently reported for conventional MFC (0.95 mW/m(2)
      for polyaniline-coated and 1.3 mW/m(2) for polypyrrole-coated anodes). However,
      the PMFC did not depend on an organic substrate as an energy source and was
      powered only by light energy. Its operation was CO(2)-neutral and did not require
      buffers or exogenous electron transfer shuttles.

PMID- 19575442
TI  - A biomimetic tubular scaffold with spatially designed nanofibers of protein/PDS
      bio-blends.
AB  - Electrospun tubular conduit (4 mm inner diameter) based on blends of
      polydioxanone (PDS II(R)) and proteins such as gelatin and elastin having a
      spatially designed trilayer structure was prepared for arterial scaffolds. SEM
      analysis of scaffolds showed random nanofibrous morphology and well
      interconnected pore network. Due to protein blending, the fiber diameter was
      reduced from 800-950 nm range to 300-500 nm range. Fourier-transform infrared
      spectroscopy (FTIR) and differential scanning calorimetry (DSC) results confirmed
      the blended composition and crystallinity of fibers. Pure PDS scaffold under
      hydrated state exhibited a tensile strength of 5.61 +/- 0.42 MPa and a modulus of
      17.11 +/- 1.13 MPa with a failure strain of 216.7 +/- 13%. The blending of PDS
      with elastin and gelatin has decreased the tensile properties. A trilayer tubular
      scaffold was fabricated by sequential electrospinning of blends of
      elastin/gelatin, PDS/elastin/gelatin, and PDS/gelatin (EG/PEG/PG) to mimic the
      complex matrix structure of native arteries. Under hydrated state, the trilayer
      conduit exhibited tensile properties (tensile strength of 1.77 +/- 0.2 MPa and
      elastic modulus of 5.74 +/- 3 MPa with a failure strain of 75.08 +/- 10%)
      comparable to those of native arteries. In vitro degradation studies for up to 30
      days showed about 40% mass loss and increase in crystallinity due to the removal
      of proteins and "cleavage-induced crystallization" of PDS.

PMID- 19575443
TI  - Fluorescence optical detection in situ for real-time monitoring of cytochrome
      P450 enzymatic activity of liver cells in multiple microfluidic devices.
AB  - We describe an in situ fluorescence optical detection system to demonstrate real
      time and non-invasive detection of reaction products in a microfluidic device
      while under perfusion within a standard incubator. The detection system is
      designed to be compact and robust for operation inside a mammalian cell culture
      incubator for quantitative detection of fluorescent signal from microfluidic
      devices. When compared to a standard plate reader, both systems showed similar
      biphasic response curves with two linear regions. Such a detection system allows
      real-time measurements in microfluidic devices with cells without perturbing the
      culture environment. In a proof-of-concept experiment, the cytochrome P450
      1A1/1A2 activity of a hepatoma cell line (HepG2/C3A) was monitored by measuring
      the enzymatic conversion of ethoxyresorufin to resorufin. The hepatoma cell line
      was embedded in Matrigel(TM) construct and cultured in a microfluidic device with
      medium perfusion. The response of the cells, in terms of P450 1A1/1A2 activity,
      was significantly different in a plate well system and the microfluidic device.
      Uninduced cells showed almost no activity in the plate assay, while uninduced
      cells in Matrigel(TM) with perfusion in a microfluidic device showed high
      activity. Cells in the plate assay showed a significant response to induction
      with 3-Methylcholanthrene while cells in the microfluidic device did not respond
      to the inducer. These results demonstrate that the system is a potentially useful
      method to measure cell response in a microfluidic system.

PMID- 19575444
TI  - Induction of mammalian cell death by simple shear and extensional flows.
AB  - In this work we investigated whether the type of shear flow, to which cells are
      exposed, influences the initiation of cell death. It is shown that mammalian
      cells, indeed, distinguish between discrete types of flow and respond
      differently. Two flow devices were employed to impose accurate hydrodynamic flow
      fields: uniform steady simple shear flow and oscillating extensional flow. To
      distinguish between necrotic and apoptotic cell death, fluorescence activated
      cell sorting and the release of DNA in the culture supernatant was used. Results
      show that Chinese Hamster Ovaries and Human Embryonic Kidney cells will enter the
      apoptotic pathway when subjected to low levels of hydrodynamic stress (around 2.0
      Pa) in oscillating, extensional flow. In contrast, necrotic death prevails when
      the cells are exposed to hydrodynamic stresses around 1.0 Pa in simple shear flow
      or around 500 Pa in extensional flow. These threshold values at which cells enter
      the respective death pathway should be avoided when culturing cells for
      recombinant protein production to enhance culture longevity and productivity.

PMID- 19575446
TI  - On old and new comparative neurological sinners: the evolutionary importance of
      the membranous parts of the actinopterygian forebrain and their sites of
      attachment.
AB  - The forebrain of actinopterygian fishes differs from that of other vertebrates in
      that it consists of a pair of solid lobes. Lateral ventricles surrounded by
      nervous tissue are entirely lacking. This peculiar configuration of the
      actinopterygian forebrain results from an outward bending or eversion of its
      lateral walls during ontogenesis. Due to this eversion, the telencephalic roof
      plate is transformed into a wide, membranous structure that surrounds the dorsal
      and lateral parts of the solid lobes and is attached to their lateral or
      ventrolateral aspects. Another effect of the eversion is that the ventricular
      surface of the telencephalic lobes is very extensive, whereas their meningeal
      surface is small. In many recent publications on the forebrain of actinopterygian
      fishes, these structures are presented as solid lobes, without any reference to
      the fact that they are the product of an eversion process, and without any
      indication concerning the location and extent of their ventricular and meningeal
      surfaces. It is explained here that, in light of current concepts concerning the
      histogenesis of the brain, these omissions are intolerable. It is also strongly
      recommended that the location and extent of these surfaces should always be
      clearly indicated in brain sections in general, because the simple notion that in
      the brain of vertebrates the ventricular surface is on the inside and the
      meningeal surface on the outside has numerous and notable exceptions.

PMID- 19575445
TI  - Blood vessels form a migratory scaffold in the rostral migratory stream.
AB  - In adult mice, new neurons born in the subventricular zone (SVZ), lining the
      lateral ventricles, migrate tangentially into the olfactory bulb along a well
      delineated path, the rostral migratory stream (RMS). Neuroblasts in the RMS
      migrate tangentially in chains, without a recognized migratory scaffold. Here we
      quantitatively examine the distribution of, and relationships between, cells
      within the RMS, throughout its rostral-caudal extent. We show that there is a
      higher density of blood vessels in the RMS than in other brain regions, including
      areas with equal cell density, and that the orientation of blood vessels
      parallels the RMS throughout the caudal to rostral path. Of particular interest,
      migratory neuroblast chains are longitudinally aligned along blood vessels within
      the RMS, with over 80% of vessel length in rostral areas of the RMS apposed by
      neuroblasts. Electron micrographs show direct contact between endothelial cells
      and neuroblasts, although intervening astrocytic processes are often present.
      Within the RMS, astrocytes arborize extensively, extending long processes that
      are parallel to blood vessels and the direction of neuroblast migration. Thus,
      the astrocytic processes establish a longitudinal alignment within the RMS,
      rather than a more typical stellate shape. This complementary alignment suggests
      that blood vessels and astrocytes may cooperatively establish a scaffold for
      migrating neuroblasts, as well as provide and regulate migratory cues.

PMID- 19575447
TI  - Sexual dimorphism and hormone responsiveness in the spinal cord of the socially
      monogamous prairie vole (Microtus ochrogaster).
AB  - Prairie voles (Microtus ochrogaster) are exceptional among rodents in that many
      aspects of their brain and behavior are not masculinized by exogenous
      aromatizable androgens. However, the sexually differentiated endpoints studied to
      date rely on estrogenic mechanisms in other mammals. We examined whether sexual
      differentiation of an androgen receptor-dependent sex difference would be
      similarly distinct in prairie voles. Male mammals have more and larger
      motoneurons projecting to perineal muscles than do females. This sex difference
      normally arises from males' perinatal androgen exposure and can be eliminated by
      treating developing females with androgens. Gross dissection revealed
      bulbospongiosus muscles in adult male, but not female, prairie voles. Retrograde
      tracing from males' bulbocavernosus muscles and the external anal sphincter from
      both sexes revealed sexually dimorphic populations of labeled motoneurons in the
      ventral horn of the lumbar spinal cord. Similar to other rodents, males had twice
      as many motoneurons as females, although no sex difference in motoneuron size was
      detected. Unexpectedly, prenatal or early postnatal exposure to testosterone
      propionate had no effect on adult females' motoneuron number or size. In
      adulthood, gonadectomy alone or followed by chronic testosterone treatment also
      had no effect on females' motoneuron size or number, although castration reduced
      motoneuron size in males. Comparing gonadally intact weanlings confirmed that the
      sex difference in motoneuron number exists before adulthood. As with some other
      sexually dimorphic traits, and perhaps related to their unique social
      organization, sexual differentiation of the prairie vole spinal cord differs from
      that found in most other laboratory rodents.

PMID- 19575448
TI  - Projections from the accessory olfactory organ into the medial region of the
      olfactory bulb in the sea lamprey (Petromyzon marinus): a novel vertebrate
      sensory structure?
AB  - Although four different primary olfactory pathways have been described in
      tetrapod vertebrates, polymorphic olfactory sensory neurons comingle in the
      olfactory epithelium and project axons into separate bulbar regions in teleost
      fish. However, spatially segregated neurons may exist in the peripheral olfactory
      organ of lampreys, extant representatives of ancestral jawless vertebrates. In
      lampreys, the caudoventral portion of the peripheral olfactory organ contains
      tubular diverticula, named the accessory olfactory organ (AOO). Short, ciliated
      AOO cells were retrogradely labelled following application of biocytin or
      carbocyanine dyes to the medial region of the olfactory bulb. Tracer application
      to eight radial locations within the layer of glomeruli with mitral cells, of the
      olfactory bulb, showed that AOO projections were restricted to the medial region
      of the olfactory bulb. The outer boundary of the AOO projection extended to the
      ventromedial region of glomerular neuropil in 43% of the specimens. The olfactory
      sensory neurons in the main olfactory epithelium projected to glomerular neuropil
      throughout the olfactory bulb, including sparse projections to the medial region
      of the olfactory bulb. This study shows that these AOO neurons and their
      projections in the medial region of the olfactory bulb are anatomically distinct
      regions of the primary olfactory pathway in the sea lamprey.

PMID- 19575449
TI  - Thymus cell antigen-1-expressing cells in the oval cell compartment.
AB  - Thymus cell antigen-1 (Thy-1)-expressing cells proliferate in the liver during
      oval cell (OC)-mediated liver regeneration. We characterized these cells in
      normal liver, in carbon tetrachloride-injured liver, and in several models of OC
      activation. The gene expression analyses were performed using reverse
      transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR (Q-RT-PCR)
      of cells isolated by fluorescence-activated cell sorting (FACS), and by
      immunofluorescent microscopy of tissue sections and isolated cells. In normal
      liver, Thy-1(+) cells are a heterogeneous population: those located in the
      periportal region do not coexpress desmin or alpha smooth muscle actin (alpha
      SMA). The majority of Thy-1(+) cells located at the lobular interface and in the
      parenchyma coexpress desmin but not alpha-SMA, i.e., they are not resident
      myofibroblasts. Although Thy-1(+) cells proliferate moderately after carbon
      tetrachloride injury, in all models of OC-mediated liver regeneration they
      proliferate quickly and expand significantly and disappear from the liver when
      the OC response subsides. Activated Thy-1(+) cells do not express OC genes but
      they express genes known to be expressed in mesenchymal stem cells (CD105, CD73,
      CD29), genes considered specific for activated stellate cells (desmin, collagen I
      a2, Mmp2, Mmp14) and myofibroblasts (alpha-SMA, fibulin-2), as well as growth
      factors and cytokines (Hgf, Tweak, IL-1b, IL-6, IL-15) that can affect OC growth.
      Activated in vitro stellate cells do not express Thy-1. Subcloning of Thy-1(+)
      cells from OC-activated livers yield Thy-1(+) fibroblastic cells and a population
      of E-cadherin(+) mesenchymal cells that gradually discontinue expression of Thy-1
      and begin to express cytokeratins. However, upon transplantation these cells do
      not differentiate into hepatocytes or cholangiocytes. Activated Thy-1(+) cells
      produce predominantly latent transforming growth factor beta. CONCLUSION: Thy
      1(+) cells in the OC niche are activated mesenchymal-epithelial cells that are
      distinct from resident stellate cells, myofibroblasts, and oval cells.

PMID- 19575450
TI  - Immunotoxin-induced ablation of melanopsin retinal ganglion cells in a non-murine
      mammalian model.
AB  - In mammals, non-image-forming visual functions, including circadian
      photoentrainment and the pupillary light reflex, are thought to be mediated by
      the combination of rods, cones, and the melanopsin-expressing intrinsically
      photosensitive retinal ganglion cells (ipRGCs). Although several genetic models
      have been developed to clarify the individual roles of the rod, cone, and ipRGC
      systems in mediating non-image visual function, assessing the in vivo role(s) of
      the ipRGCs has been complicated by the possibility of ontogenetic issues in these
      genetically modified animal models. In the present study, we describe the
      development and validation of an immunotoxin that specifically targets the ipRGC
      population in the mature mammalian retina. This ipRGC immunotoxin, consisting of
      saporin conjugated to a melanopsin polyclonal antibody, was evaluated with
      respect to its effectiveness and specificity in depleting the ipRGC population in
      the fully developed rat retina. The results showed that the ipRGC toxin rapidly
      and permanently depleted approximately 70% of the ipRGC population, without
      inducing appreciable changes in the cell number or morphology of any of the non
      melanopsin-containing retinal cell populations investigated. These findings
      suggest that the newly developed ipRGC immunotoxin provides a potent method for
      achieving relatively rapid, permanent, and selective depletion of the ipRGC
      population in a non-murine model system. The development of this ipRGC-ablation
      method is the next step in elucidating the role of ipRGCs in mediating non-visual
      and circadian light-resetting responses in a wide range of non-murine mammalian
      models.

PMID- 19575452
TI  - Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons
      and are activated by agonists of protease-activated receptor 2.
AB  - Serine proteases generated during injury and inflammation cleave protease
      activated receptor 2 (PAR(2)) on primary sensory neurons to induce neurogenic
      inflammation and hyperalgesia. Hyperalgesia requires sensitization of transient
      receptor potential vanilloid (TRPV) ion channels by mechanisms involving
      phospholipase C and protein kinase C (PKC). The protein kinase D (PKD)
      serine/threonine kinases are activated by diacylglycerol and PKCs and can
      phosphorylate TRPV1. Thus, PKDs may participate in novel signal transduction
      pathways triggered by serine proteases during inflammation and pain. However, it
      is not known whether PAR(2) activates PKD, and the expression of PKD isoforms by
      nociceptive neurons is poorly characterized. By using HEK293 cells transfected
      with PKDs, we found that PAR(2) stimulation promoted plasma membrane
      translocation and phosphorylation of PKD1, PKD2, and PKD3, indicating activation.
      This effect was partially dependent on PKCepsilon. By immunofluorescence and
      confocal microscopy, with antibodies against PKD1/PKD2 and PKD3 and neuronal
      markers, we found that PKDs were expressed in rat and mouse dorsal root ganglia
      (DRG) neurons, including nociceptive neurons that expressed TRPV1, PAR(2), and
      neuropeptides. PAR(2) agonist induced phosphorylation of PKD in cultured DRG
      neurons, indicating PKD activation. Intraplantar injection of PAR(2) agonist also
      caused phosphorylation of PKD in neurons of lumbar DRG, confirming activation in
      vivo. Thus, PKD1, PKD2, and PKD3 are expressed in primary sensory neurons that
      mediate neurogenic inflammation and pain transmission, and PAR(2) agonists
      activate PKDs in HEK293 cells and DRG neurons in culture and in intact animals.
      PKD may be a novel component of a signal transduction pathway for protease
      induced activation of nociceptive neurons and an important new target for
      antiinflammatory and analgesic therapies.

PMID- 19575453
TI  - Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in
      hepatocytes.
AB  - Hepatic insulin resistance is a major contributor to fasting hyperglycemia in
      patients with metabolic syndrome and type 2 diabetes. Circumstantial evidence
      suggests that cyclooxygenase products in addition to cytokines might contribute
      to insulin resistance. However, direct evidence for a role of prostaglandins in
      the development of hepatic insulin resistance is lacking. Therefore, the impact
      of prostaglandin E(2) (PGE(2)) alone and in combination with interleukin-6 (IL-6)
      on insulin signaling was studied in primary hepatocyte cultures. Rat hepatocytes
      were incubated with IL-6 and/or PGE(2) and subsequently with insulin. Glycogen
      synthesis was monitored by radiochemical analysis; the activation state of
      proteins of the insulin receptor signal chain was analyzed by western blot with
      phosphospecific antibodies. In hepatocytes, insulin-stimulated glycogen synthesis
      and insulin-dependent phosphorylation of Akt-kinase were attenuated
      synergistically by prior incubation with IL-6 and/or PGE(2) while insulin
      receptor autophosphorylation was barely affected. IL-6 but not PGE(2) induced
      suppressors of cytokine signaling (SOCS3). PGE(2) but not IL-6 activated
      extracellular signal-regulated kinase 1/2 (ERK1/2) persistently. Inhibition of
      ERK1/2 activation by PD98059 abolished the PGE(2)-dependent but not the IL-6
      dependent attenuation of insulin signaling. In HepG2 cells expressing a
      recombinant EP3-receptor, PGE(2) pre-incubation activated ERK1/2, caused a serine
      phosphorylation of insulin receptor substrate 1 (IRS1), and reduced the insulin
      dependent Akt-phosphorylation. CONCLUSION: PGE(2) might contribute to hepatic
      insulin resistance via an EP3-receptor-dependent ERK1/2 activation resulting in a
      serine phosphorylation of insulin receptor substrate, thereby preventing an
      insulin-dependent activation of Akt and glycogen synthesis. Since different
      molecular mechanisms appear to be employed, PGE(2) may synergize with IL-6, which
      interrupted the insulin receptor signal chain, principally by an induction of
      SOCS, namely SOCS3.

PMID- 19575454
TI  - Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: a
      prospective magnetic resonance imaging and histological study.
AB  - The development of sclerosing cholangitis (SC) is observed in up to 50% of
      children followed up for autoimmune hepatitis (AIH). In adults, the prevalence is
      less known, although a recent study found evidence of SC in 10% of AIH patients
      using magnetic resonance cholangiopancreatography (MRCP). The aim of this study
      was to assess prospectively the prevalence of SC in adults with AIH. Fifty-nine
      consecutive patients with AIH diagnosed according to International Autoimmune
      Hepatitis Group score (women, 71%; mean age, 48 years; cirrhosis, 23%) underwent
      both MRCP and percutaneous liver biopsy. Twenty-seven patients with cirrhosis of
      nonbiliary or non-autoimmune etiology served as controls. Fourteen AIH patients
      (24%) showed mild MRCP abnormalities of intrahepatic bile ducts (IHBDs). None had
      abnormal common bile duct or convincing evidence of SC on MRCP or biopsy. A
      diagnosis of overlapping SC was nevertheless retained in one patient with MRCP
      abnormalities who subsequently developed symptomatic cholestasis despite
      corticosteroid therapy. Fibrosis score was the only independent parameter
      associated with bile duct abnormalities on MRCP (odds ratio 2.4; 95% confidence
      interval 1.4-4.7) and the percentage of patients with IHBD MRCP abnormalities was
      not different among F3-F4 AIH patients (n = 24) and cirrhotic controls (46%
      versus 59%; NS). CONCLUSION: In this cohort of adult patients with AIH, the
      prevalence of SC was much lower than previously reported (1.7%). Mild MRCP
      abnormalities of IHBD were seen in a quarter of patients, but these abnormalities
      resulted from hepatic fibrosis and not SC. In the absence of cholestatic
      presentation, MRCP screening does not seem justified in adult-onset AIH.

PMID- 19575455
TI  - Hypothyroidism and hepatocellular carcinoma: more questions than answers.

PMID- 19575456
TI  - Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T
      cell tolerance to antigens targeting murine liver.
AB  - The mechanisms of tolerance in the liver that limit susceptibility to food
      allergy and that mediate the acceptance of liver transplants, even with a
      complete major histocompatibility complex (MHC) mismatch, remain poorly defined.
      Here we report that in a model of liver-directed gene transfer, cytotoxic T
      lymphocyte (CTL) responses to non-self antigens are controlled by hepatic
      regulatory T cells (Tregs) that secrete the immunosuppressive cytokine
      interleukin (IL)-10 in response to the antigen. In addition, Kupffer cells (KCs),
      normally thought to initiate immune responses, are rendered tolerogenic in this
      context. The depletion of KCs results in a complete abrogation of IL-10
      production by hepatic Tregs, indicating an interaction between Tregs and KCs in
      the induction of tolerance. CONCLUSION: Our study suggests that hepatic Tregs
      together with KCs create a local suppressive microenvironment that prevents the
      establishment of the CTL response. These mechanisms provide pivotal insights and
      may prove instrumental in the tolerization toward non-self therapeutic proteins
      delivered to the liver.

PMID- 19575457
TI  - Diagnostic value and utility of the simplified International Autoimmune Hepatitis
      Group (IAIHG) criteria in acute and chronic liver disease.
AB  - Diagnostic criteria for autoimmune hepatitis (AIH) have been created and revised
      by the International Autoimmune Hepatitis Group (IAIHG). Simplified criteria have
      been created, but remain independently unvalidated. We report on the diagnostic
      accuracy of the simplified criteria in patients across a range of diagnoses,
      including a subset of patients presenting with fulminant liver failure who
      required liver transplant. Patients with AIH and non-AIH etiologies of liver
      disease were identified from dedicated patient databases. Parameters relevant to
      the simplified and 1999 IAIHG criteria were recorded, and sensitivity,
      specificity, and positive and negative predictive values for scores of >or=6
      (probable AIH) and >or=7 (definite AIH) were calculated. A total of 549 patients
      with chronic liver disease were evaluated, (221 with AIH, 26 with variant
      syndromes, and 302 with non-AIH). For scores >or=6, sensitivity was 90%, and
      specificity was 98% with positive and negative predictive values of 97% and 92%,
      respectively. For scores >or=7; sensitivity was 70%, and specificity was 100%
      with positive and negative predictive values of 100% and 74%, respectively. Seven
      false positive diagnoses of AIH occurred, all with simplified scores of 6.
      Concordance with 1999 criteria was 90% for probable and 61% for definite AIH. The
      frequency of an overall diagnosis of AIH (probable or definite AIH) among the 70
      patients with fulminant liver failure was 24% for simplified criteria and 40% for
      1999 criteria, respectively. CONCLUSION: The simplified criteria retain high
      specificity but exhibit lower sensitivity for scores of >or=7. The explanations
      for this are unclear but may relate to loss of such discriminating information as
      response to corticosteroids. Prospective evaluation of these criteria is required
      to corroborate these observations.

PMID- 19575458
TI  - Hepatic failure due to hepatitis B reactivation in a patient with ulcerative
      colitis treated with prednisone.

PMID- 19575459
TI  - A stimulus needed for the study of membrane traffic in hepatocytes.

PMID- 19575460
TI  - Enhanced liver regeneration following changes induced by hepatocyte-specific
      genetic ablation of integrin-linked kinase.
AB  - Following liver regeneration after partial hepatectomy, liver grows back
      precisely to its original mass and does not exceed it. The mechanism regulating
      this "hepatostat" is not clear and no exceptions have been found to date.
      Although pathways initiating liver regeneration have been well studied,
      mechanisms involved in the termination of liver regeneration are unclear. Here,
      we report that integrin-linked kinase (ILK) (involved in transmission of the
      extracellular matrix [ECM] signaling by way of integrin receptors) and/or hepatic
      adaptations that ensue following ILK hepatocyte-targeted removal are critical for
      proper termination of liver regeneration. Following partial hepatectomy (PHx),
      mice with a liver-specific ILK ablation (ILK-KO-Liver) demonstrate a termination
      defect resulting in 58% larger liver than their original pre-PHx mass. This
      increase in post-PHx liver mass is due to sustained cell proliferation driven in
      part by increased signaling through hepatocyte growth factor (HGF), and the beta
      catenin pathway and Hippo kinase pathways. CONCLUSION: The data indicate that ECM
      mediated signaling by way of ILK is essential in proper termination of liver
      regeneration. This is the first evidence of a defect leading to impaired
      termination of regeneration and excessive accumulation of liver weight following
      partial hepatectomy.

PMID- 19575461
TI  - Cellulose hydrolysis in evolving substrate morphologies I: A general modeling
      formalism.
AB  - We develop a general framework for a realistic rate equation modeling of
      cellulose hydrolysis using non-complexed cellulase. Our proposed formalism, for
      the first time, takes into account explicitly the time evolution of the random
      substrate morphology resulting from the hydrolytic cellulose chain fragmentation
      and solubilization. This is achieved by integrating novel geometrical concepts to
      quantitatively capture the time-dependent random morphology, together with the
      enzymatic chain fragmentation, into a coupled morphology-plus-kinetics rate
      equation approach. In addition, an innovative site number representation, based
      on tracking available numbers of beta(1,4) glucosidic bonds, of different "site"
      types, exposed to attacks by different enzyme types, is presented. This site
      number representation results in an ordinary differential equation (ODE) system,
      with a substantially reduced ODE system size, compared to earlier chain
      fragmentation kinetics approaches. This formalism enables us to quantitatively
      simulate both the hydrolytically evolving random substrate morphology and the
      profound, and heretofore neglected, morphology effects on the hydrolysis
      kinetics. By incorporating the evolving morphology on an equal footing with the
      hydrolytic chain fragmentation, our formalism provides a framework for the
      realistic modeling of the entire solubilization process, beyond the short-time
      limit and through near-complete hydrolytic conversion. As part I of two companion
      papers, the present paper focuses on the development of the general modelling
      formalism. Results and testable experimental predictions from detailed numerical
      simulations are presented in part II.

PMID- 19575462
TI  - Endotoxemia and gut barrier dysfunction in alcoholic liver disease.

PMID- 19575463
TI  - Enantiodiscrimination of methamphetamine by circular dichroism using a porphyrin
      tweezer.
AB  - Using exciton-coupled circular dichroism (ECCD) spectroscopy, our lab was able to
      differentiate between the two enantiomers of methamphetamine using a commercially
      available porphyrin tweezer as an achiral host. The host-guest complex formed
      with (+)-(S)-methamphetamine produced a negative bisignate-shaped ECCD spectrum,
      whereas the complex formed with (-)-(R)-methamphetamine produced a positive one.
      This sensitive technique could serve as an alternative method for the
      enantiodiscrimination of chiral methamphetamine, a commonly abused drug in the
      United States.

PMID- 19575464
TI  - Stereoselective transport and uptake of propranolol across human intestinal Caco
      2 cell monolayers.
AB  - The transport and uptake of individual propranolol (PPL) enantiomers were studied
      in human intestinal Caco-2 cell monolayers, and a reversed-phase HPLC-UV assay
      was used for quantitative analysis. S-PPL and R-PPL across Caco-2 cell monolayers
      was determined in the concentrations range of 10-500 microM in both apical (AP)
      to basolateral (BL) and BL to AP directions. S-PPL exhibited greater permeability
      than R-PPL in the AP to BL direction, whereas in the BL to AP direction S
      enantiomer transported less than R-enantiomer. Uptake of R-PPL was significantly
      higher than that of S-PPL either from AP side or from BL side. The statistically
      significant differences in uptake were observed at the concentrations range from
      10 to 50 microM. Furthermore, the apparent Michaelis constant (K(m)) and maximal
      velocity (V(max)) also showed significant difference between the two enantiomers.
      Moreover, the AP to BL transport of PPL enantiomer was markedly decreased by
      lowering the pH of the apical side but it did not affect the stereoselectivity of
      PPL across Caco-2 cell monolayers. The transport and uptake of PPL in the BL to
      AP direction was not influenced by several protein inhibitors. The results
      suggest that PPL enantiomers showed stereoselective transport and uptake across
      the Caco-2 cell monolayers. A special transport mechanism capable of directing
      the PPL enantiomers might be present in the Caco-2 monolayers.

PMID- 19575465
TI  - Acute toxicity of two CdSe/ZnSe quantum dots with different surface coating in
      Daphnia magna under various light conditions.
AB  - With an increasing use of quantum dots (QDs) in many applications, their
      potential hazard is of growing concern. However, little is known about their
      ecotoxicity, especially in vivo. In the present study, we employed freshwater
      macroinvertebrate, Daphnia magna, to evaluate toxicity characteristics of cadmium
      selenide/zinc selenide (CdSe/ZnSe) in relation to surface coatings, e.g.,
      mercaptopropionic acid QD ((MPA)QD), and gum arabic/tri-n-octylphosphine oxide QD
      ((GA/TOPO)QD), and light conditions, i.e., dark, fluorescent light, environmental
      level of ultraviolet (UV) light, and sunlight. The results of the present study
      showed that D. magna was more susceptible to (GA/TOPO)QD exposure compared to
      (MPA)QD. The surface coating of QD appeared to determine the stability of QDs and
      hence the toxicity, potentially by size change of or the release of toxic
      components from QDs. However, (GA/TOPO)QD was still less toxic than the
      equivalent level of CdCl2. The toxicity of all the tested compounds increased by
      changing the light condition from dark to white fluorescence to UV-B light, and
      to natural sunlight. The effect of light condition on QDs toxicity could also be
      explained by photostability of the QDs, which would affect size of the particle,
      release of toxic component ions, and generation of reactive oxygen species.
      Considering increasing use of QDs in various applications, their environmental
      fates and corresponding toxic potentials deserve further investigation.

PMID- 19575466
TI  - Simultaneous determination of enantiomerization and hydrolysis kinetic parameters
      of chiral N-alkylbenzothiadiazine derivatives.
AB  - On-column stopped flow multidimensional HPLC (sfMDHPLC) and dynamic high
      performance liquid chromatography were applied to investigate the influence of
      alkyl substituents at the sulfonamidic and amino moieties of benzothiadiazine 1,1
      dioxide derivatives on hydrolysis and enantiomerization rate constants. The data
      obtained indicate the presence of pyrrolo substituent at the 3,4 positions on
      benzothiadiazine rings inhibits the hydrolysis, whereas the enantiomerization
      occurs in acidic medium. Hydrolysis rates are quite similar for the two
      benzothiadiazines methyl substituted to nitrogen at 2- and 4-positions.
      Conversely, enantiomerization rate of 4-N-methyl substituted is significantly
      higher than 2-N-methyl substituted.

PMID- 19575467
TI  - CHARMM general force field: A force field for drug-like molecules compatible with
      the CHARMM all-atom additive biological force fields.
AB  - The widely used CHARMM additive all-atom force field includes parameters for
      proteins, nucleic acids, lipids, and carbohydrates. In the present article, an
      extension of the CHARMM force field to drug-like molecules is presented. The
      resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical
      groups present in biomolecules and drug-like molecules, including a large number
      of heterocyclic scaffolds. The parametrization philosophy behind the force field
      focuses on quality at the expense of transferability, with the implementation
      concentrating on an extensible force field. Statistics related to the quality of
      the parametrization with a focus on experimental validation are presented.
      Additionally, the parametrization procedure, described fully in the present
      article in the context of the model systems, pyrrolidine, and 3
      phenoxymethylpyrrolidine will allow users to readily extend the force field to
      chemical groups that are not explicitly covered in the force field as well as add
      functional groups to and link together molecules already available in the force
      field. CGenFF thus makes it possible to perform "all-CHARMM" simulations on drug
      target interactions thereby extending the utility of CHARMM force fields to
      medicinally relevant systems.

PMID- 19575469
TI  - Assessing reproductive status/stages in mice.
AB  - The short reproductive cycle length observed in rodents, called the estrous
      cycle, makes them an ideal animal model for investigation of changes that occur
      during the reproductive cycle. Most of the data in the literature about the
      estrous cycle is obtained from rats because they are easily manipulated and they
      exhibit a clear and well-defined estrous cycle. However, the increased number of
      experiments using knockout mice requires identification of their estrous cycle as
      well, since (in)fertility issues may arise. In mice, like rats, the
      identification of the stage of estrous cycle is based on the proportion of cell
      types observed in the vaginal secretion. The aim of this unit is to provide
      guidelines for quickly and accurately determining estrous cycle phases in mice.

PMID- 19575470
TI  - Identification of neural programmed cell death through the detection of DNA
      fragmentation in situ and by PCR.
AB  - Programmed cell death is a fundamental process for the development and somatic
      maintenance of organisms. This unit describes methods for visualizing both dying
      cells in situ and for detection of nucleosomal ladders. A description of various
      current detection strategies is provided, as well as support protocols for
      preparing positive and negative controls and for preparing genomic DNA.

PMID- 19575468
TI  - Simultaneous optical mapping of intracellular free calcium and action potentials
      from Langendorff perfused hearts.
AB  - The cardiac action potential (AP) controls the rise and fall of intracellular
      free Ca2+ (Ca(i)), and thus the amplitude and kinetics of force generation.
      Besides excitation-contraction coupling, the reverse process where Ca(i)
      influences the AP through Ca(i)-dependent ionic currents has been implicated as
      the mechanism underlying QT alternans and cardiac arrhythmias in heart failure,
      ischemia/reperfusion, cardiac myopathy, myocardial infarction, congenital and
      drug-induced long QT syndrome, and ventricular fibrillation. The development of
      dual optical mapping at high spatial and temporal resolution provides a powerful
      tool to investigate the role of Ca(i) anomalies in eliciting cardiac arrhythmias.
      This unit describes experimental protocols to map APs and Ca(i) transients from
      perfused hearts by labeling the heart with two fluorescent dyes, one to measure
      transmembrane potential (Vm), the other Ca(i) transients. High spatial and
      temporal resolution is achieved by selecting Vm and Ca(i) probes with the same
      excitation but different emission wavelengths, to avoid cross-talk and mechanical
      components.

PMID- 19575471
TI  - Production of polyclonal antisera.
AB  - Much of modern biology and biochemistry relies on the availability of highly
      specific antibodies for use in such ubiquitous techniques as
      immunohistochemistry, ELISAs, immunoprecipitation, and immunoblotting. Thus, the
      generation of large quantities of specific antibodies directed against proteins
      or peptides of interest is essential to the success of both basic and applied
      research programs. In addition, with the advent of antibody-based proteomic
      strategies for profiling protein expression and post-translational modification,
      a requirement for timely production of specific antibodies has been exemplified.
      Polyclonal antibodies derived from animals immunized with purified proteins or
      peptides are particularly valuable for use in the laboratory. This unit provides
      protocols for the production of polyclonal antisera specific for protein antigens
      using rabbits, rats, mice, and hamsters.

PMID- 19575472
TI  - Measurement of oxygen radicals and lipid peroxidation in neural tissues.
AB  - One of the most completely validated processes involved in secondary tissue
      damage following acute brain or spinal cord injury and in many chronic
      neurodegenerative diseases has to do with the pathological formation of reactive
      oxygen species (ROS) and reactive nitrogen species (RNS). These are generated by
      multiple mechanisms and give rise to highly reactive oxygen radicals that can
      damage neuronal, glial, and microvascular elements. Particular interest has
      centered upon oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) as
      the principal mechanism of neuronal injury associated with oxygen radicals. Thus,
      there has been a growing interest in monitoring increased oxygen radical levels
      as an index of oxidative stress, as well as measuring markers of LP-associated
      oxidative injury in in vitro and in vivo model systems and neurological patient
      samples. Accordingly, the purpose of this unit is to provide a variety of methods
      for the measurement of hydroxyl radical formation and/or LP in nervous tissue or
      biofluids.

PMID- 19575473
TI  - Detection and quantification of neurotransmitters in dialysates.
AB  - Sensitive analytical methods are needed for the separation and quantification of
      neurotransmitters obtained in microdialysate studies. This unit describes methods
      that permit quantification of nanomolar concentrations of monoamines and their
      metabolites (high-pressure liquid chromatography electrochemical detection),
      acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids (HPLC
      fluorescence detection; capillary electrophoresis with laser-induced fluorescence
      detection).

PMID- 19575474
TI  - Simple behavioral assessment of mouse olfaction.
AB  - This unit presents two basic protocols that offer rapid assessments of anosmia
      (the absence of a sense of smell) in mice. The buried food test is used to check
      for the ability to smell volatile odors. The olfactory habituation/dishabituation
      test is used to test whether the animal can detect and differentiate different
      odors, including both nonsocial and social odors. A non-contact method of odor
      presentation, along with a general method for collecting urine samples, is given
      as an alternate protocol. The tests described in this unit only require simple
      equipment and can be adopted readily by most laboratories.

PMID- 19575475
TI  - Pathway modulators and inhibitors.
AB  - Inhibitors of specific cellular pathways are useful for investigating the roles
      of proteins of unknown function, and for selectively inhibiting a protein in
      complex pathways to uncover its relationships to other proteins in this and other
      interacting pathways. This appendix provides links to Web sites that describe
      cellular processes and pathways along with the various classes of inhibitors,
      numerous references, downloadable diagrams, and technical tips.

PMID- 19575476
TI  - Metabolic radiolabeling of animal cell glycoconjugates.
AB  - Useful information about glycoconjugates can be obtained by labeling their
      aglycone (noncarbohydrate) portions--e.g., labeling proteins with radioactive
      amino acids--and then using techniques described elsewhere in this chapter to
      infer the presence, type, and nature of glycan chains. This unit describes
      metabolic labeling techniques that provide more specific information about the
      structure, sequence, and distribution of the sugar chains of glycoconjugates.
      Following metabolic labeling, the radioactive glycoconjugate of interest is
      isolated, individual glycosylation sites are identified and separated if
      necessary, and the labeled glycans are subjected to structural analysis.

PMID- 19575477
TI  - Resources for small regulatory RNAs.
AB  - In the past fifteen years, new classes of regulatory RNAs have been discovered,
      previously hidden in the transcriptome mostly due to their small size. These
      small regulatory RNAs include small interfering RNAs (siRNAs), microRNAs
      (miRNAs), and Piwi-interacting RNAs (piRNAs). Numerous databases have been
      developed to store information about these small regulatory RNAs, and many tools
      have been developed to work with the data. This overview introduces the reader to
      the many resources available for working with small regulatory RNAs.

PMID- 19575478
TI  - Directed evolution of proteins in vitro using compartmentalization in emulsions.
AB  - This unit describes a protocol for the directed evolution of proteins utilizing
      in vitro compartmentalization. This method uses a large number of independent in
      vitro transcription and translation (IVTT) reactions in water droplets suspended
      in an oil emulsion to enable selection of proteins that bind a target molecule.
      Protein variants that bind the target also bind to and allow recovery of the
      genes that encoded them. This protocol serves as a basis for carrying out
      selections in emulsions, and can potentially be modified to select for other
      functionalities, including catalysis. This selection method is advantageous
      compared to alternative selection protocols due to the ability to screen through
      very large-size libraries and the ability to express and screen or select for
      functions that would otherwise be toxic or inaccessible to in vivo selections and
      screens.

PMID- 19575479
TI  - Laser microdissection-mediated isolation and in vitro transcriptional
      amplification of plant RNA.
AB  - Protocols for laser microdissection and linear amplification of RNA from fixed,
      sectioned plant tissues are described. When combined with quantitative RT-PCR,
      microarray analysis, or RNA-sequencing, these procedures enable quantitative
      analyses of transcript accumulation from microscopic quantities of specific plant
      organs, tissues, or single cells.

PMID- 19575481
TI  - C-X...O halogen bonding: interactions of trifluoromethyl halides with dimethyl
      ether.
AB  - The formation of weakly bound molecular complexes between dimethyl ether (DME)
      and the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I dissolved in liquid
      argon and in liquid krypton is investigated, using Raman and FTIR spectroscopy.
      For all halides evidence is found for the formation of C-X...O halogen-bonded 1:1
      complexes. At higher concentrations of CF(3)Br, a weak absorption due to a 1:2
      complex is also observed. Using spectra recorded at temperatures between 87 and
      125 K, the complexation enthalpies for the complexes are determined to be -6.8(3)
      kJ mol(-1) (DME x CF(3)Cl), -10.2(1) kJ mol(-1) (DME x CF(3)Br), -15.5(1) kJ mol(
      1) (DME x CF(3)I), and -17.8(5) kJ mol(-1) [DME(x CF(3)Br)(2)]. Structural and
      spectral information on the complexes is obtained from ab initio calculations at
      the MP2/6-311++G(d,p) and MP2/6-311++G(d,p)+LanL2DZ* levels. By applying Monte
      Carlo free energy perturbation calculations to account for the solvent
      influences, and statistical thermodynamics to estimate the zero-point vibrational
      and thermal influences, the ab initio complexation energies are converted into
      complexation enthalpies for the solutions in liquid argon. The resulting values
      are compared with the experimental data deduced from the cryosolutions.

PMID- 19575480
TI  - Fed-batch methanol feeding strategy for recombinant protein production by Pichia
      pastoris in the presence of co-substrate sorbitol.
AB  - Batch-wise sorbitol addition as a co-substrate at the induction phase of methanol
      fed-batch fermentation by Pichia pastoris (Mut(+)) was proposed as a beneficial
      recombinant protein production strategy and the metabolic responses to methanol
      feeding rate in the presence of sorbitol was systematically investigated. Adding
      sorbitol batch-wise to the medium provided the following advantages over growth
      on methanol alone: (a) eliminating the long lag-phase for the cells and reaching
      'high cell density production' at t = 24 h of the process (C(X) = 70 g CDW/l);
      (b) achieving 1.8-fold higher recombinant human erythropoietin (rHuEPO) (at t =
      18 h); (c) reducing specific protease production 1.2-fold; (d) eliminating the
      lactic acid build-up period; (e) lowering the oxygen uptake rate two-fold; and
      (f) obtaining 1.4-fold higher overall yield coefficients. The maximum specific
      alcohol oxidase activity was not affected in the presence of sorbitol, and it was
      observed that sorbitol and methanol were utilized simultaneously. Thus, in the
      presence of sorbitol, 130 mg/l rHuEPO was produced at t = 24 h, compared to 80
      mg/l rHuEPO (t = 24 h) on methanol alone. This work demonstrates not only the
      ease and efficiency of incorporating sorbitol to fermentations by Mut(+) strains
      of P. pastoris for the production of any bio-product, but also provides new
      insights into the metabolism of the methylotrophic yeast P. pastoris.

PMID- 19575482
TI  - Geometric model describing the banded morphology of particle films formed by
      convective assembly.
AB  - Nanoparticle films coated on smooth substrates by convective assembly from dilute
      suspensions in dip-coating configuration are known to have discrete film
      morphologies. Specifically, the film morphology is characterized by alternating
      bands of densely packed particles and bands of bare substrate. Convective
      assembly is a frontal film-growth process that occurs at the three-phase contact
      line formed by the substrate, the suspension in which it is submersed, and the
      surrounding air. The bands are parallel to this contact line and can be either
      monolayered or multilayered. Monolayered bands result whenever the substrate is
      withdrawn from the suspension at a rate too high for particles to assemble into a
      continuous film. We report a new insight to the mechanism behind this banding
      phenomenon, namely, that inter-band spacing is strongly influenced by the
      constituent particle size. We therefore propose a geometric model relating the
      inter-band spacing to the particle size. By making banded films with
      systematically varied particle sizes (silica/zeolite, 20 to 500 nm), we are able
      to quantitatively validate our model. Furthermore, the model correctly predicts
      that multilayered banded films have higher inter-band spacings than monolayered
      banded films comprising the same particles.

PMID- 19575483
TI  - A strategy for producing pure single-layer graphene sheets based on a confined
      self-assembly approach.

PMID- 19575484
TI  - Biomolecule-functionalized nanowires: from nanosensors to nanocarriers.
AB  - The unique properties of nanowires offer excellent prospects for designing a new
      generation of devices and systems exhibiting novel functions. This Review
      discusses recent scientific accomplishments in the preparation of nanowire
      biomaterial hybrids and their potential applications as nanosensors,
      nanoactuators, and nanocarriers. Nanowires can be readily functionalized with
      various biochemicals through different linkage chemistries. Such integration of
      nanowires and biomolecules leads to novel hybrid systems which couple the
      recognition or catalytic properties of biomaterials with the attractive
      electronic and structural characteristics of nanowires. Receptor-functionalized
      nanowires are particularly attractive for direct real-time label-free electrical
      detection of biomolecular interactions. The unique control over the
      microstructure of nanowires, and particularly the design of multisegment
      nanowires, offer spatially defined regions for the defined organization of
      different biomolecules. This allows the resulting nanowires to perform several
      tasks simultaneously, and opens the door to a variety of important applications
      in the areas of nanobioelectronics and nanomedicine. For example, multisegment
      nanowires designed for nanomedicine applications can couple the selective
      targeting, therapy, and imaging functions. Such spatially defined anchoring of
      different biorecognition sites provides also distinct opportunities for the self
      assembly of nanowires into predetermined designs. The opportunities and
      challenges involved in designing such nanowire-biomaterial hybrid systems and
      devices are discussed in the following sections.

PMID- 19575485
TI  - Developing multicomponent interventions using fractional factorial designs.
AB  - Multicomponent interventions composed of behavioral, delivery, or implementation
      factors in addition to medications are becoming increasingly common in health
      sciences. A natural experimental approach to developing and refining such
      multicomponent interventions is to start with a large number of potential
      components and screen out the least active ones. Factorial designs can be used
      efficiently in this endeavor. We address common criticisms and misconceptions
      regarding the use of factorial designs in these screening studies. We also
      provide an operationalization of screening studies. As an example, we consider
      the use of a screening study in the development of a multicomponent smoking
      cessation intervention. Simulation results are provided to support the
      discussions.

PMID- 19575486
TI  - A systematic review of the efficacy and safety of herbal medicines used in the
      treatment of obesity.
AB  - This review focuses on the efficacy and safety of effective herbal medicines in
      the management of obesity in humans and animals. PubMed, Scopus, Google Scholar,
      Web of Science, and IranMedex databases were searched up to December 30, 2008.
      The search terms were "obesity" and ("herbal medicine" or "plant", "plant
      medicinal" or "medicine traditional") without narrowing or limiting search
      elements. All of the human and animal studies on the effects of herbs with the
      key outcome of change in anthropometric measures such as body weight and waist
      hip circumference, body fat, amount of food intake, and appetite were included.
      In vitro studies, reviews, and letters to editors were excluded. Of the
      publications identified in the initial database, 915 results were identified and
      reviewed, and a total of 77 studies were included (19 human and 58 animal
      studies). Studies with Cissus quadrangularis (CQ), Sambucus nigra, Asparagus
      officinalis, Garcinia atroviridis, ephedra and caffeine, Slimax (extract of
      several plants including Zingiber officinale and Bofutsushosan) showed a
      significant decrease in body weight. In 41 animal studies, significant weight
      loss or inhibition of weight gain was found. No significant adverse effects or
      mortality were observed except in studies with supplements containing ephedra,
      caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQ,
      ginseng, bitter melon, and zingiber were found to be effective in the management
      of obesity. Attention to these natural compounds would open a new approach for
      novel therapeutic and more effective agents.

PMID- 19575488
TI  - Molecular characteristics and stages of chronic hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial
      health burden worldwide. Remarkable progress has been made in our understanding
      of the natural stages of chronic HBV infection. A dynamic balance between viral
      replication and host immune response is pivotal to the pathogenesis of liver
      disease. Knowledge of the HBV genome organization and replication cycle can
      unravel HBV genotypes and molecular variants, which contribute to the
      heterogeneity in outcome of chronic HBV infection. Most HBV infections are
      spontaneously resolved in immunocompetent adults, whereas they become chronic in
      most neonates and infants at a great risk of developing complications such as
      cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection
      may present in one of the four phases of infection: immune tolerance, immune
      clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB)],
      inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the
      dynamic nature of chronic HBV infection is crucial in the management of HBV
      carriers. Long-term monitoring and optimal timing of antiviral therapy for
      chronic HBV infection help to prevent progression of HBV-related liver disease to
      its later stage, particularly in patients with higher risk markers of HCC, such
      as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes,
      and pre-core or core mutants.

PMID- 19575489
TI  - Constructive thinking, rational intelligence and irritable bowel syndrome.
AB  - AIM: To evaluate rational and experiential intelligence in irritable bowel
      syndrome (IBS) sufferers. METHODS: We recruited 100 subjects with IBS as per Rome
      II criteria (50 consulters and 50 non-consulters) and 100 healthy controls,
      matched by age, sex and educational level. Cases and controls completed a
      clinical questionnaire (including symptom characteristics and medical
      consultation) and the following tests: rational-intelligence (Wechsler Adult
      Intelligence Scale, 3rd edition); experiential-intelligence (Constructive
      Thinking Inventory); personality (NEO personality inventory); psychopathology
      (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social
      readjustment rating scale). Analysis of variance was used to compare the test
      results of IBS-sufferers and controls, and a logistic regression model was then
      constructed and adjusted for age, sex and educational level to evaluate any
      possible association with IBS. RESULTS: No differences were found between IBS
      cases and controls in terms of IQ (102.0 +/- 10.8 vs 102.8 +/- 12.6), but IBS
      sufferers scored significantly lower in global constructive thinking (43.7 +/-
      9.4 vs 49.6 +/- 9.7). In the logistic regression model, global constructive
      thinking score was independently linked to suffering from IBS [OR 0.92 (0.87
      0.97)], without significant OR for total IQ. CONCLUSION: IBS subjects do not show
      lower rational intelligence than controls, but lower experiential intelligence is
      nevertheless associated with IBS.

PMID- 19575487
TI  - An overview of animal models for investigating the pathogenesis and therapeutic
      strategies in acute hepatic failure.
AB  - Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic
      encephalopathy which causes multiorgan failure with an extremely high mortality
      rate, even if intensive care is provided. Management of severe AHF continues to
      be one of the most challenging problems in clinical medicine. Liver
      transplantation has been shown to be the most effective therapy, but the
      procedure is limited by shortage of donor organs. Although a number of clinical
      trials testing different liver assist devices are under way, these systems alone
      have no significant effect on patient survival and are only regarded as a useful
      approach to bridge patients with AHF to liver transplantation. As a result,
      reproducible experimental animal models resembling the clinical conditions are
      still needed. The three main approaches used to create an animal model for AHF
      are: surgical procedures, toxic liver injury and infective procedures. Most
      common models are based on surgical techniques (total/partial hepatectomy,
      complete/transient devascularization) or the use of hepatotoxic drugs
      (acetaminophen, galactosamine, thioacetamide, and others), and very few
      satisfactory viral models are available. We have recently developed a viral model
      of AHF by means of the inoculation of rabbits with the virus of rabbit
      hemorrhagic disease. This model displays biochemical and histological
      characteristics, and clinical features that resemble those in human AHF. In the
      present article an overview is given of the most widely used animal models of
      AHF, and their main advantages and disadvantages are reviewed.

PMID- 19575490
TI  - Enhancement patterns of pancreatic adenocarcinoma on conventional dynamic multi
      detector row CT: correlation with angiogenesis and fibrosis.
AB  - AIM: To evaluate retrospectively the correlation between enhancement patterns on
      dynamic computed tomography (CT) and angiogenesis and fibrosis in pancreatic
      adenocarcinoma. METHODS: Twenty-three patients with pancreatic adenocarcinoma
      underwent dynamic CT and tumor resection. In addition to the absolute and
      relative enhanced value that was calculated by subtracting the attenuation value
      on pre-contrast from those on contrast-enhanced CT in each phase, we defined one
      parameter, "tumor-aorta enhancement ratio", which was calculated by dividing
      enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase.
      These enhancement patterns were correlated with the level of vascular endothelial
      growth factor (VEGF), microvessel density (MVD), and extent of fibrosis. RESULTS:
      The absolute enhanced value in the arterial phase correlated with the level of
      VEGF and MVD (P = 0.047, P = 0.001). The relative enhanced value in arterial
      phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P =
      0.003, P = 0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively
      with the extent of fibrosis (P = 0.004). The tumors with greater MVD and higher
      expression of VEGF tended to show high enhancement in the arterial dominant
      phase. On the other hand, the tumors with a larger amount of fibrosis showed a
      negative correlation with the grade of enhancement during the arterial phase.
      CONCLUSION: Enhancement patterns on dynamic CT correlated with angiogenesis and
      may be modified by the extent of fibrosis.

PMID- 19575491
TI  - Microscopic colitis: a large retrospective analysis from a health maintenance
      organization experience.
AB  - AIM: To examine the demographic data on a large multi-ethnic population of
      patients with microscopic colitis (MC) in Southern California and to determine
      the association of MC with inflammatory bowel disease (IBD) and colorectal
      cancer. METHODS: All patients diagnosed with MC by colonic biopsy from 1996-2005
      were identified utilizing a pathology database. All biopsies were reviewed by
      experienced pathologists utilizing standard histologic criteria. Patients'
      medical records were reviewed and data regarding patient age, co-morbidities,
      sex, ethnicity, and medications were analyzed. An age- and sex-matched standard
      control group was also generated. Chi-square test was used to evaluate the
      associations of co-morbidities between lymphocytic colitis (LC), collagenous
      colitis (CC) and the control group. RESULTS: A total of 547 cases of MC were
      identified, 376 patients with LC and 171 patients with CC. The female/male ratio
      was 3:1 in CC and 2.7:1 in LC patients. Celiac disease (P < 0.001), irritable
      bowel syndrome (IBS) (P < 0.001), and thyroid diseases (P < 0.001) were found to
      have a higher occurrence in MC compared to the control group. No statistical
      differences in the occurrence of colorectal cancer, diabetes and IBD were found
      between the MC group and the control group. CONCLUSION: This is the largest group
      of patients with MC known to the authors that has been studied to date.
      Conditions such as celiac disease, IBS, and thyroid diseases were found to be
      related to MC. Furthermore, neither an increased risk of colorectal cancer nor
      IBD was associated with MC in this study.

PMID- 19575492
TI  - Portal hypertension secondary to myelofibrosis with myeloid metaplasia: a study
      of 13 cases.
AB  - AIM: To describe the clinical presentation and complications of portal
      hypertension (PH) secondary to myelofibrosis with myeloid metaplasia (MMM).
      METHODS: Medical records for 123 patients with MMM were reviewed. RESULTS:
      Thirteen patients with PH secondary to MMM were identified. Median ages at time
      of MMM and PH diagnosis were 61 and 66 years, respectively. The interval from MMM
      diagnosis to presentation with one of the PH features ranged from 1 to 11 years.
      Variceal bleeding and ascites were the most common presentations. Of the eight
      patients who presented with variceal bleeding, six patients underwent endoscopic
      variceal ligation (EVL) with no variceal recurrence or hematological worsening
      during a 12-mo follow up period. CONCLUSION: Patients with MMM might develop PH.
      Exact mechanisms leading to PH in MMM are still controversial. As in other
      etiologies, variceal bleeding and ascites are the most common presentations.
      Anemia may correlate with, and/or predict, the severity of the PH presentation in
      these patients. EVL can successfully control variceal bleeding in MMM. Further
      clinical studies are required.

PMID- 19575493
TI  - Serum bile acid profiling reflects enterohepatic detoxification state and
      intestinal barrier function in inflammatory bowel disease.
AB  - AIM: To determine free and conjugated serum bile acid (BA) levels in inflammatory
      bowel disease (IBD) subgroups with defined clinical manifestations. METHODS:
      Comprehensive serum BA profiling was performed in 358 IBD patients and 310
      healthy controls by liquid chromatography coupled to electrospray ionization
      tandem mass spectrometry. RESULTS: Serum levels of hyodeoxycholic acid, the
      CYP3A4-mediated detoxification product of the secondary BA lithocholic acid
      (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis
      (UC), while most other serum BA species were decreased significantly. Total BA,
      total BA conjugate, and total BA glycoconjugate levels were decreased only in CD,
      whereas total unconjugated BA levels were decreased only in UC. In UC patients
      with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid,
      taurocholic acid, and glycochenodeoxycholic acid were as significantly increased
      as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid
      compared to UC patients without hepatobiliary manifestations. Finally, we found
      that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid
      and chenodeoxycholic acid, were increased significantly compared to controls and
      patients without surgical interventions. CONCLUSION: Serum BA profiling in IBD
      patients that indicates impaired intestinal barrier function and increased
      detoxification is suitable for advanced diagnostic characterization and
      differentiation of IBD subgroups with defined clinical manifestations.

PMID- 19575494
TI  - Human papilloma virus and esophageal carcinoma in a Latin-American region.
AB  - AIM: To investigate the presence of high-risk human papilloma virus (HPV) in
      esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.
      METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the
      esophagus were obtained from Department of Pathology files, at the National
      Cancer Institute in Mexico City during the period between 2000 and 2008. Slides
      from each case were reviewed and cases with sufficient neoplastic tissue were
      selected for molecular analysis. DNA was extracted from paraffin-embedded tissue
      samples for polymerase chain reaction analysis to detect HPV DNA sequences.
      Demographic and clinical data of each patient were retrieved from corresponding
      clinical records. RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the
      most frequently observed genotype, followed by HPV-18; HPV-59 was also detected
      in one case. Unfortunately, HPV genotype could not be established in three cases
      due to lack of material for direct sequencing, although universal primers
      detected the presence of HPV generic sequences. No low-risk HPV genotypes were
      found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly
      associated with gender, age, alcohol consumption, smoking, anatomic location, or
      histologic grade. All patients belonged to low and very low socioeconomic strata,
      and were diagnosed at advanced disease stage. Male patients were most commonly
      affected and the male:female ratio in HPV-positive ESCC increased two-fold in
      comparison with HPV-negative cases (6.5:1 vs 3.1:1). CONCLUSION: High prevalence
      of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV
      associated ESCC is more common in areas with higher ESCC incidence rates.

PMID- 19575495
TI  - Is percutaneous endoscopic gastrostomy tube placement safe in patients with
      ventriculoperitoneal shunts?
AB  - AIM: To investigate whether percutaneous endoscopic gastrostomy (PEG) tube
      placement is safe in patients with ventriculoperitoneal (VP) shunts. METHODS:
      This was a retrospective study of all patients undergoing PEG insertion at our
      institution between June 1999 and June 2006. Post-PEG complications were compared
      between two groups according to the presence or absence of VP shunts. VP shunt
      infection rates, the interval between PEG placement and VP shunt catheter
      insertion, and long-term follow-up were also investigated. RESULTS: Fifty-five
      patients qualified for the study. Seven patients (12.7%) had pre-existing VP
      shunts. All patients received prophylactic antibiotics. The complication rate did
      not differ between VP shunt patients undergoing PEG (PEG/VP group) and non-VP
      shunt patients undergoing PEG (control group) [1 (14.3%) vs 6 (12.5%), P =
      1.000]. All patients in the PEG/VP group had undergone VP shunt insertion prior
      to PEG placement. The mean interval between VP shunt insertion and PEG placement
      was 308.7 d (range, 65-831 d). The mean follow-up duration in the PEG/VP group
      was 6.4 mo (range, 1-15 mo). There were no VP shunt infections, although one
      patient in the PEG/VP group developed a minor peristomal infection during follow
      up. CONCLUSION: Complications following PEG placement in patients with VP shunts
      were infrequent in this study.

PMID- 19575496
TI  - What is the most cost-effective strategy to screen for second primary colorectal
      cancers in male cancer survivors in Korea?
AB  - AIM: To identify a cost-effective strategy of second primary colorectal cancer
      (CRC) screening for cancer survivors in Korea using a decision-analytic model.
      METHODS: A Markov model estimated the clinical and economic consequences of a
      simulated 50-year-old male cancer survivors' cohort, and we compared the results
      of eight screening strategies: no screening, fecal occult blood test (FOBT)
      annually, FOBT every 2 years, sigmoidoscopy every 5 years, double contrast barium
      enema every 5 years, and colonoscopy every 10 years (COL10), every 5 years
      (COL5), and every 3 years (COL3). We included only direct medical costs, and our
      main outcome measures were discounted lifetime costs, life expectancy, and
      incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis,
      the non-dominated strategies in cancer survivors were COL5, and COL3. The ICER
      for COL3 in cancer survivors was $5593/life-year saved (LYS), and did not exceed
      $10,000/LYS in one-way sensitivity analyses. If the risk of CRC in cancer
      survivors is at least two times higher than that in the general population, COL5
      had an ICER of less than $10,500/LYS among both good and poor prognosis of index
      cancer. If the age of cancer survivors starting CRC screening was decreased to 40
      years, the ICER of COL5 was less than $7400/LYS regardless of screening
      compliance. CONCLUSION: Our study suggests that more strict and frequent
      recommendations for colonoscopy such as COL5 and COL3 could be considered as
      economically reasonable second primary CRC screening strategies for Korean male
      cancer survivors.

PMID- 19575497
TI  - Characterization of clarithromycin resistance in Malaysian isolates of
      Helicobacter pylori.
AB  - AIM: To characterize the types of mutations present in the 23S rRNA genes of
      Malaysian isolates of clarithromycin-resistant Helicobacter pylori (H pylori).
      METHODS: Clarithromycin susceptibility of H pylori isolates was determined by E
      test. Analyses for point mutations in the domain V of 23S rRNA genes in
      clarithromycin-resistant and -sensitive strains were performed by sequence
      analysis of amplified polymerase chain reaction products. Restriction fragment
      length polymorphism was performed using BsaI and MboII enzymes to detect
      restriction sites that correspond to the mutations in the clarithromycin
      resistant strains. RESULTS: Of 187 isolates from 120 patients, four were
      resistant to clarithromycin, while 183 were sensitive. The MIC of the resistant
      strains ranged from 1.5 to 24 microg/mL. Two isolates had an A2142G mutation and
      another two had A2143G mutations. A T2182C mutation was detected in two out of
      four clarithromycin-resistant isolates and in 13 of 14 clarithromycin-sensitive
      isolates. Restriction enzyme analyses with BsaI and MboII were able to detect the
      mutations. CONCLUSION: Clarithromycin resistance is an uncommon occurrence among
      Malaysian isolates of H pylori strains and the mutations A2142G and A2143G
      detected were associated with low-level resistance.

PMID- 19575498
TI  - Cardiopulmonary bypass induced microcirculatory injury of the small bowel in
      rats.
AB  - AIM: To investigate microvascular injury quantitatively in the small bowel with
      respect to cardiopulmonary bypass (CPB) and related mechanisms. METHODS: In 10
      male SD rats, normothermic CPB was established and continued with a flow rate of
      100-150 mL/kg per minute for 60 min, while another 10 sham-operated animals
      served as controls. An approximate 10-cm loop of the terminal ileum was
      exteriorized for observation by means of intravital fluorescence microscopy. The
      small bowel microcirculatory network including arterioles, capillaries, and
      collecting venules was observed prior to CPB, CPB 30 min, CPB 60 min, post-CPB 60
      min and post-CPB 120 min. The intestinal capillary perfusion, microvascular
      permeability and leukocyte adherence were also measured. RESULTS: The systemic
      hemodynamics remained stable throughout the experiment in both groups. In CPB
      animals, significant arteriolar vasoconstriction, blood velocity reduction and
      functional capillary density diminution were found. As concomitances, exaggerated
      albumin extravasation and increased leukocyte accumulation were also noted. These
      changes were more pronounced and there were no signs of restitution at the end of
      the observation period. CONCLUSION: CPB induces significant microcirculatory
      injury of the small bowel in rats. The major underlying mechanisms are blood flow
      redistribution and generalized inflammatory response associated with CPB.

PMID- 19575499
TI  - Translation and validation of the Nepean Dyspepsia Index for functional dyspepsia
      in China.
AB  - AIM: To assess the reliability and validity of the translated version of Nepean
      Dyspepsia Index (NDI) in Chinese patients with documented functional dyspepsia
      (FD). METHODS: The translation process included forward translation, back
      translation, pretest and cross-cultural adaptation. Reliability and validity of
      the translated version were examined by asking 300 subjects to complete the
      Chinese version of the NDI. The mean age of subjects was 39.24 years and 68.7% of
      the subjects were women. Internal consistency analysis with Cronbach's alpha was
      performed to test the reliability. Correlation analysis was used to assess the
      content validity. Factor analysis and structural equation models were used to
      assess the construct validity. RESULTS: The Cronbach's alpha coefficients ranged
      0.833-0.960, well above the acceptable level of 0.70. Correlation analysis showed
      that each item had a strong correlation with the corresponding domain, but a weak
      correlation with other domains. Confirmatory factor analysis indicated that the
      comparative fit index was 0.94, higher than the acceptable level of 0.90.
      CONCLUSION: The Chinese version of the NDI is a reliable and valid scale for
      measuring health-related quality of life and disease severity in Chinese patients
      with FD.

PMID- 19575500
TI  - Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis
      C virus-core protein: a potential for developing hepatitis C virus targeting gene
      therapy.
AB  - AIM: To examine whether 2'-5'oligoadenylate synthetase (OAS) gene promoter can be
      specifically activated by hepatitis C virus (HCV)-core protein. METHODS: Human
      embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and
      selected by G418. Expression of HCV-core was detected by reverse transcription
      polymerase chain reaction and Western blotting. The OAS promoter sequence was
      amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant
      pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and
      luciferase activity was assayed. RESULTS: L02/core cell line stably expressing
      HCV-core protein was established. The pGL3-OAS-Luci construct exhibited
      significant transcriptional activity in the L02/core cells but not in the L02
      cells. CONCLUSION: HCV-core protein activates the OAS gene promoter specifically
      and effectively. Utilization of OAS gene promoter would be an ideal strategy for
      developing HCV-specific gene therapy.

PMID- 19575501
TI  - Improved quality of life in patients with gastric cancer after
      esophagogastrostomy reconstruction.
AB  - AIM: To compare postoperative quality of life (QOL) in patients with gastric
      cancer treated by esophagogastrostomy reconstruction after proximal gastrectomy.
      METHODS: QOL assessments that included functional outcomes (a 24-item survey
      about treatment-specific symptoms) and health perception (Spitzer QOL Index) were
      performed in 149 patients with gastric cancer in the upper third of the stomach,
      who had received proximal gastrectomy with additional esophagogastrostomy.
      RESULTS: Fifty-four patients underwent reconstruction by esophagogastric anterior
      wall end-to-side anastomosis combined with pyloroplasty (EA group); 45 patients
      had reconstruction by esophagogastric posterior wall end-to-side anastomosis (EP
      group); and 50 patients had reconstruction by esophagogastric end-to-end
      anastomosis (EE group). The EA group showed the best postoperative QOL, such as
      recovery of body weight, less discomfort after meals, and less heart burn or
      belching at 6 and 24 mo postoperatively. However, the survival rates, surgical
      results and Spitzer QOL index were similar among the three groups. CONCLUSION:
      Postoperative QOL was better in the EA than EP or EE group. To improve QOL after
      proximal gastrectomy for upper third gastric cancer, the EA procedure using a
      stapler is safe and feasible for esophagogastrostomy.

PMID- 19575502
TI  - Enigma of primary aortoduodenal fistula.
AB  - A diagnosis of primary aortoenteric fistula is difficult to make despite a high
      level of clinical suspicion. It should be considered in any elderly patient who
      presents with upper gastrointestinal bleeding in the context of a known abdominal
      aortic aneurysm. We present the case of young man with no history of abdominal
      aortic aneurysm who presented with massive upper gastrointestinal bleeding.
      Initial misdiagnosis led to a delay in treatment and the patient succumbing to
      the illness. This case is unique in that the fistula formed as a result of
      complex atherosclerotic disease of the abdominal aorta, and not from an aneurysm.

PMID- 19575503
TI  - Pentoxifylline: a first line treatment option for severe alcoholic hepatitis and
      hepatorenal syndrome?
AB  - Although favourable results of pentoxifylline (PTX) used in treatment of severe
      alcoholic hepatitis patients with a Maddrey discriminant function score > or = 32
      have been previously reported, it is not currently recommended as a first line
      treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as
      compared to the standard treatment with corticosteroids. In a very recent issue
      of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the
      first time the two treatment modalities head to head in a randomized controlled
      study, demonstrating the advantage of PTX over corticosteroids in terms of
      patients' survival and risk-benefit profile. The advantage of PTX over
      corticosteroids in survival of patients with severe alcoholic hepatitis was found
      to be related to the prevention of hepatorenal syndrome in their study. This
      study raises the question of the use of PTX as a standard treatment for severe
      alcoholic hepatitis. Considering the fact that PTX presented a spectacular
      efficiency in prevention of hepatorenal syndrome in their study as well as that
      previous studies have shown that this effect is possibly related to a primary
      renoprotective action because it is irrelevant of tumor necrosis factor-alpha
      synthesis inhibition or improved liver function, we tempted to speculate that PXT
      might be an effective option for prevention and/or treatment of hepatorenal
      syndrome complicating other forms of advanced liver disease. This attractive
      theory remains to be elucidated by pressing future studies in view of the lack of
      effective treatment modalities for hepatorenal syndrome.

PMID- 19575504
TI  - Neuromodulation of epileptic foci in patients with non-lesional refractory motor
      epilepsy.
AB  - We report two cases of chronic therapeutic stimulation of epileptic foci
      localized in motor areas. Case 1 is an adolescent with supplementary motor area
      seizures whose intracranial recordings showed a right SMA focus. Case 2 is a
      female teenager with primary motor seizures originating in the right motor cortex
      in the hand area as shown by her intracranial recordings and cortical mapping.
      Both had apparently normal MRI. Chronic stimulation of the epileptic focus
      decreased the number of seizures more than 90% the seizure number while
      preserving motor function. None of the patients had side effects. Neuromodulation
      is proposed as a safe, efficient surgical alternative for motor seizure control.

PMID- 19575505
TI  - Seizure abatement with single dc pulses: is phase resetting at play?
AB  - Topological approaches for seizure abatement have received scarce attention. The
      ability to reset the phase of biological oscillations has been widely exploited
      in cardiology, as evidenced in part by the usefulness of implantable of
      defibrillators, but not in epileptology. The aim of this work is to investigate
      the feasibility of seizure blockage using single or brief monophasic (DC) pulse
      trains. Single DC or brief (0.1 s) pulse trains were delivered manually or
      automatically to generalized seizures, induced in rats with the convulsant 3
      mercaptoprionic acid, a GABA inhibitor. Treatment outcome (blocked vs. not
      blocked seizures) was ascertained visually and correlated with the "rhythmicity
      index", an indirect estimate of neuronal synchrony level. Blockage using single
      or brief (0.1 s) DC pulses was consistently achieved for seizures with a
      rhythmicity index > 0.6, while seizures with levels <0.6 were not, although
      transient phase changes in their oscillations were effected. This work reveals
      that level of neuronal synchronization may be an important factor in determining
      the probability of seizure blockage. Seizure blockage using single or brief DC
      pulse trains and its effects on neural tissue merit further investigation. The
      clinical applicability of this therapeutic modality and means to enhance it are
      discussed.

PMID- 19575506
TI  - Non-invasive computerized system for automatically initiating vagus nerve
      stimulation following patient-specific detection of seizures or epileptiform
      discharges.
AB  - OBJECTIVE: To demonstrate the feasibility of using a computerized system to
      detect the onset of a seizure and, in response, initiate Vagus nerve stimulation
      (VNS) in patients with medically refractory epilepsy. METHODS: We designed and
      built a non-invasive, computerized system that automatically initiates VNS
      following the real-time detection of a pre-identified seizure or epileptiform
      discharge. The system detects these events through patient-specific analysis of
      the scalp electroencephalogram (EEG) and electrocardiogram (ECG) signals.
      RESULTS: We evaluated the performance of the system on 5 patients (A-E). For
      patients A and B the computerized system initiated VNS in response to seizures;
      for patients C and D the system initiated VNS in response to epileptiform
      discharges; and for patient E neither seizures nor epileptiform discharges were
      observed during the evaluation period. During the 81 hour clinical test of the
      system on patient A, the computerized system detected 5/5 seizures and initiated
      VNS within 5 seconds of the appearance of ictal discharges in the EEG; VNS did
      not seem to alter the electrographic or behavioral characteristics of the
      seizures in this case. During the same testing session the computerized system
      initiated false stimulations at the rate of 1 false stimulus every 2.5 hours
      while the subject was at rest and not ambulating. During the 26 hour clinical
      test of the system on patient B, the computerized system detected 1/1 seizures
      and initiated VNS within 16 seconds of the appearance of ictal discharges; VNS
      did not alter the electrographic duration of the seizure but decreased anxiety
      and increased awareness during the post-seizure recovery phase. During the same
      testing session the computerized system did not declare any false detections.
      SIGNIFICANCE: Initiating Vagus nerve stimulation soon after the onset of a
      seizure may abort or ameliorate seizure symptoms in some patients; unfortunately,
      a significant number of patients cannot initiate VNS by themselves following the
      start of a seizure. A system that automatically couples automated detection of
      seizure onset to initiation of VNS may be helpful for seizure treatment.

PMID- 19575507
TI  - Control of synchronization of brain dynamics leads to control of epileptic
      seizures in rodents.
AB  - We have designed and implemented an automated, just-in-time stimulation, seizure
      control method using a seizure prediction method from nonlinear dynamics coupled
      with deep brain stimulation in the centromedial thalamic nuclei in epileptic
      rats. A comparison to periodic stimulation, with identical stimulation
      parameters, was also performed. The two schemes were compared in terms of their
      efficacy in control of seizures, as well as their effect on synchronization of
      brain dynamics. The automated just-in-time (JIT) stimulation showed reduction of
      seizure frequency and duration in 5 of the 6 rats, with significant reduction of
      seizure frequency (>50%) in 33% of the rats. This constituted a significant
      improvement over the efficacy of the periodic control scheme in the same animals.
      Actually, periodic stimulation showed an increase of seizure frequency in 50% of
      the rats, reduction of seizure frequency in 3 rats and significant reduction in 1
      rat. Importantly, successful seizure control was highly correlated with
      desynchronization of brain dynamics. This study provides initial evidence for the
      use of closed-loop feedback control systems in epileptic seizures combining
      methods from seizure prediction and deep brain stimulation.

PMID- 19575509
TI  - Deep brain stimulation for the treatment of epilepsy.
AB  - During the last decade, deep brain stimulation (DBS) has been used to treat
      several neurologic disorders, including epilepsy. Promising results have been
      reported with stimulation in different brain regions. At present however, several
      issues remain unanswered. As an example, it is still unclear whether particular
      seizure types and syndromes should be treated with DBS in different targets or
      with different stimulation parameters. In addition, clinical,
      electrophysiological and anatomical features capable of predicting a good
      postoperative outcome are still unknown. We review the published literature on
      DBS, cortical and cerebellar stimulation for the treatment of epilepsy focusing
      predominantly on the rationale and clinical outcome in each target.

PMID- 19575508
TI  - Calibration of neurotransmitter release from neural cells for therapeutic
      implants.
AB  - In this work we quantified the in vitro calibration relationships between high
      frequency electrical stimulation and GABA and glutamate release in both mature
      retinoic acid differentiated P19 neurons and immortalized embryonic cortical
      cells engineered to express glutamic acid decarboxylase, GAD65. Extracellular
      glutamate and GABA was quantified by 2D gas chromatography and time of flight
      mass spectrometry after stimulation at varying amplitudes and frequencies.
      Amplitude sweeps resulted in a linear calibration for P19 neurons; the level of
      neurotransmitter varied over one order of magnitude from ~ 200 pg/neuron to ~ 1.2
      ng/neuron for glutamate and ~ 1 ng/neuron to ~ 2 ng/neuron for GABA, depending on
      the stimulation amplitude. Frequency sweeps resulted in a peak release at 250 Hz
      for glutamate and 400 Hz for GABA in P19 cells. The GABA transporter inhibitor,
      nipecotic acid, increased extracellular GABA levels and decrease glutamate. In
      contrast the embryonic cortical cells had a strongly nonlinear dependency of
      release on stimulation amplitude, and a weak dependence on frequency. These cells
      had roughly equal extracellular glutamate and GABA levels after stimulation
      despite the expression of GAD65. In addition glutamate and GABA levels were
      insensitive to nipecotic acid. These results demonstrate an ability to calibrate
      and tune neurotransmitter release from neural cells using high frequency
      stimulation parameters.

PMID- 19575510
TI  - Nine tips for a healthier 2009.

PMID- 19575512
TI  - Make your health information personal. Collecting your health records in one
      place is a good idea.

PMID- 19575511
TI  - Observing JUPITER.  Trial results are likely to expand statin use and testing for
      CRP.

PMID- 19575513
TI  - Changing picture of atherosclerosis. New view puts focus on improving artery
      health, not just fighting blockages.

PMID- 19575514
TI  - Navigating the ocean of health information.  Tips for searching the Internet for
      information about heart disease.

PMID- 19575515
TI  - Ask the doctor. I have coronary heart disease. Is this something I can have cured
      or get rid of, or is keeping it from getting worse the best I can do?

PMID- 19575516
TI  - Ask the doctor. I had an electrocardiogram in preparation for minor surgery. My
      doctor told me it showed that I have right bundle branch block. Neither he nor my
      cardiologist are worried about it, but I am. Is this serious?

PMID- 19575517
TI  - Bypass results vary by hospital.  Checking up on hospitals and surgeons before
      bypass surgery may pay off.

PMID- 19575518
TI  - C-reactive protein testing comes of age. Measuring low-grade inflammation can
      help refine cardiovascular risk.

PMID- 19575519
TI  - Generic heart drugs as good as brand names.  "You get what you pay for" doesn't
      apply to prescription drugs.

PMID- 19575520
TI  - Two-way street between depression and hear disease. Lifting depression can help
      the heart and mind; exercise is essential.

PMID- 19575521
TI  - Preeclampsia poses later heart risk.

PMID- 19575522
TI  - When success leads to failure.

PMID- 19575524
TI  - Bucking the trends: calories still count.  Protein, carbs, fats--specialized
      diets may work for some, but the bottom line is still calorie reduction.

PMID- 19575523
TI  - Ask the doctor.  My doctor told me I have an enlarged heart.  What is it?  What
      causes it and what does it mean for my health?

PMID- 19575525
TI  - Enhanced ovarian cancer detection.  Two-test combo may identify disease early
      enough to cure it.

PMID- 19575526
TI  - Human infection with new influenza A (H1N1) virus: WHO Consultation on suspension
      of classes and restriction of mass gatherings to mitigate the impact of epidemics
      caused by influenza A (H1N1), May 2009.

PMID- 19575527
TI  - Properties of Arg481 mutants of the aa3-type cytochrome c oxidase from
      Rhodobacter sphaeroides suggest that neither R481 nor the nearby D-propionate of
      heme a3 is likely to be the proton loading site of the proton pump.
AB  - Cytochrome c oxidase utilizes the energy from electron transfer and reduction of
      oxygen to water and pumps protons across the membrane, generating a proton motive
      force. A large body of biochemical work has shown that all the pumped protons
      enter the enzyme through the D-channel, which is apparent in X-ray structures as
      a chain of water molecules connecting D132 at the cytoplasmic surface of the
      enzyme to E286, near the enzyme active site. The exit pathway utilized by pumped
      protons beyond this point and leading to the bacterial periplasm is not known.
      Also not known is the proton loading site (or sites) which undergoes changes in
      pKa in response to the chemistry at the enzyme active site and drives the proton
      pump mechanism. In this paper, we examine the role of R481, a highly conserved
      arginine that forms an ion pair with the D-propionate of heme a3. The R481H,
      R481N, R481Q, and R481L mutants were examined. The R481H mutant oxidase is
      approximately 18% active and pumps protons with approximately 40% of the
      stoichiometry of the wild type. The R481N, R481Q, and R481L mutants each retain
      only approximately 5% of the steady-state activity, and this is shown to be due
      to inhibition of steps in the reaction of O(2) with the reduced enzyme. Neither
      the R481N mutant nor the R481Q mutant oxidases pump protons, but remarkably, the
      R481L mutant does pump protons with the same efficiency as the R481H mutant.
      Since the proton pump is clearly operating in the R481L mutant, these results
      rule out an essential role in the proton pump mechanism for R481 or its hydrogen
      bond partner, the D-propionate of heme a3.

PMID- 19575528
TI  - Binding of Pseudomonas aeruginosa apobacterioferritin-associated ferredoxin to
      bacterioferritin B promotes heme mediation of electron delivery and mobilization
      of core mineral iron.
AB  - The bfrB gene from Pseudomonas aeruginosa was cloned and expressed in Escherichia
      coli. The resultant protein (BfrB), which assembles into a 445.3 kDa complex from
      24 identical subunits, binds 12 molecules of heme axially coordinated by two Met
      residues. BfrB, isolated with 5-10 iron atoms per protein molecule, was
      reconstituted with ferrous ions to prepare samples with a core mineral containing
      600 +/- 40 ferric ions per BfrB molecule and approximately one phosphate molecule
      per iron atom. In the presence of sodium dithionite or in the presence of P.
      aeruginosa ferredoxin NADP reductase (FPR) and NADPH, the heme in BfrB remains
      oxidized, and the core iron mineral is mobilized sluggishly. In stark contrast,
      addition of NADPH to a solution containing BfrB, FPR, and the apo form of P.
      aeruginosa bacterioferritin-associated ferredoxin (apo-Bfd) results in rapid
      reduction of the heme in BfrB and in the efficient mobilization of the core iron
      mineral. Results from additional experimentation indicate that Bfd must bind to
      BfrB to promote heme mediation of electrons from the surface to the core to
      support the efficient mobilization of ferrous ions from BfrB. In this context,
      the thus far mysterious role of heme in bacterioferritins has been brought to the
      front by reconstituting BfrB with its physiological partner, apo-Bfd. These
      findings are discussed in the context of a model for the utilization of stored
      iron in which the significant upregulation of the bfd gene under low-iron
      conditions [Ochsner, U. A., Wilderman, P. J., Vasil, A. I., and Vasil, M. L.
      (2002) Mol. Microbiol. 45, 1277-1287] ensures sufficient concentrations of apo
      Bfd to bind BfrB and unlock the iron stored in its core. Although these findings
      are in contrast to previous speculations suggesting redox mediation of electron
      transfer by holo-Bfd, the ability of apo-Bfd to promote iron mobilization is an
      economical strategy used by the cell because it obviates the need to further
      deplete cellular iron levels to assemble iron-sulfur clusters in Bfd before the
      iron stored in BfrB can be mobilized and utilized.

PMID- 19575529
TI  - Comparative proteomic analysis of responses to pathogen infection and wounding in
      Fagus sylvatica.
AB  - Defense responses of Fagus sylvatica seedlings elicited by infection with the
      root pathogen Phytophthora citricola and root or leaf wounding were compared at
      local and systemic levels in differential display experiments using two
      dimensional gel electrophoresis followed by homology-driven mass spectrometric
      identification of proteins. A total of 68 protein spots were identified
      representing 51 protein functions related to protein synthesis and processing,
      energy, primary and secondary metabolism, as well as signal transduction, stress
      and defense. Changes in the abundance of root and leaf proteins partly overlapped
      between plant responses to the different stressors. The response to pathogen
      infection was rather late, weak and unspecific and accompanied by adjustments of
      the energy and primary metabolism which suggested either a lack of recognition or
      a suppression of host's defense reaction by the invading pathogen. The response
      to wounding involved changes in the basal metabolism as well as activation of
      defense mechanisms. Both types of changes were largely specific to the wounded
      organ. Similarities between the defense mechanisms activated by root infection
      and root wounding were also observed.

PMID- 19575530
TI  - Ending the "publish and vanish" culture: how the data standardization process
      will assist in data harvesting.

PMID- 19575531
TI  - Proteomics researchers solidifying principles for data sharing.

PMID- 19575532
TI  - D-penicillamine-induced autoimmunity: relationship to macrophage activation.
AB  - Idiosyncratic drug reactions represent a serious health problem, and they remain
      unpredictable largely due to our limited understanding of the mechanisms
      involved. Penicillamine-induced autoimmunity in Brown Norway (BN) rats represents
      one model of an idiosyncratic reaction, and this drug can also cause autoimmune
      reactions in humans. We previously demonstrated that penicillamine binds to
      aldehydes on the surface of macrophages. There is evidence that an imine bond
      formed by aldehyde groups on macrophages and amine groups on T cells is one type
      of interaction between these two cells that is involved in the induction of an
      immune response. We proposed that the binding of penicillamine with aldehyde
      groups on macrophages could lead to their activation and in some patients could
      lead to autoimmunity. In this study, the transcriptome profile of spleen
      macrophages 6 h after penicillamine treatment was used to detect effects of
      penicillamine on macrophages with a focus on 20 genes known to be macrophage
      activation biomarkers. One biological consequence of macrophage activation was
      investigated by determining mRNA levels for IL-15 and IL-1 beta which are crucial
      for NK cell activation, as well as levels of mRNA for selected cytokines in
      spleen NK cells. Up-regulation of the macrophage activating cytokines, IFN-gamma
      and GM-CSF, and down-regulation of IL-13 indicated activation of NK cells, which
      suggests a positive feedback loop between macrophages and NK cells. Furthermore,
      treatment of a murine macrophage cell line, RAW264.7, with penicillamine
      increased the production of TNF-alpha, IL-6, and IL-23, providing additional
      evidence that penicillamine activates macrophages. Hydralazine and isoniazid
      cause a lupus-like syndrome in humans and also bind to aldehyde groups. These
      drugs were also found to activate RAW264.7 macrophages. Together, these data
      support the hypothesis that drugs that bind irreversibly with aldehydes lead to
      macrophage activation, which in some patients can lead to an autoimmune syndrome.

PMID- 19575533
TI  - Enantioselective ring-opening reactions of racemic ethynyl epoxides via copper
      allenylidene intermediates: efficient approach to chiral beta-amino alcohols.
AB  - Enantioselective copper-catalyzed ring-opening reactions of racemic ethynyl
      epoxides with amines using (R)-DTBM-MeO-BIPHEP as a chiral ligand have been found
      to give the corresponding amino alcohols in high yields with up to 94% ee. The
      reaction is considered to proceed via copper-allenylidene complexes as key
      intermediates. This methodology may provide a novel synthetic approach to
      optically active amino alcohols, the structures of which are widely found in many
      natural products, biologically active compounds, and chiral ligands.

PMID- 19575535
TI  - Heterocyclic annelated di(perylene bisimide): constructing bowl-shaped perylene
      bisimides by the combination of steric congestion and ring strain.
AB  - In this paper, we present the synthesis of S- and N-heterocyclic annelated
      di(perylene bisimide) with extraordinary doubly bowl-shaped structures. The
      structures of fused PBI bowls confirmed by single-crystal X-ray structure
      analysis and temperature-dependent (1)H NMR are realized by the introduction of
      the steric congestion in nonbay regions and by the concurrent formation of the
      five-membered heterorings strain in bay regions. On the basis of the geometry
      obtained from the X-ray analysis, the maximum POAV1 pyramidalization angle is
      found in N-heterocyclic annelated diPBI 7, as large as 4.7 degrees , indicating
      the formation of two PBI bowls with significant curvatures. Furthermore, to
      assist the electrochemical and spectroscopic characterization of the two bowl
      shaped derivatives and to assess the influence of heteroatoms on the bowl
      curvature, quantum-chemically optimized atomic structures, electronic properties,
      and optical signatures were computed with density functional theory.

PMID- 19575534
TI  - One-pot electrochemical synthesis of fused indole derivatives containing active
      hydroxyl groups in aqueous medium.
AB  - An novel and convenient electrochemical approach was developed for the synthesis
      of indole derivatives from catechols and alpha-oxoheterocyclic ketene N,O
      acetals. This method provides an environmentally benign access to fused indole
      derivatives containing active hydroxyls and carbonyl under mild reaction
      conditions.

PMID- 19575536
TI  - Enantioselective total synthesis of the potent anti-inflammatory (+)-myrrhanol A.
AB  - The first total synthesis of potent anti-inflammatory polypodanes (+)-myrrhanol A
      (1), (+)-myrrhanone A (2), (+)-myrrhanone B (3), and (+)-myrrhanol B (4) has been
      achieved. Key steps in our convergent, highly stereocontrolled route are a
      Ti(III)-mediated radical cyclization of a chiral monoepoxide to furnish a
      bicyclic synthon that combines stereospecifically with an acyclic vinyl iodide
      via an intermolecular B-alkyl Suzuki-Miyaura cross-coupling.

PMID- 19575538
TI  - Adiabatic pathways in the conformational and geometrical photoisomerizations of
      the 1,2-distyrylbenzene isomers.
AB  - The photophysical behavior of the geometrical isomers of 1,2-distyrylbenzene (1,2
      DSB) has been investigated as a function of temperature by stationary and pulsed
      fluorimetric techniques in a nonpolar solvent. The temperature effect on the
      spectral properties, fluorescence quantum yields, and decay profiles allowed the
      role played by the conformational isomers of these molecules in the relaxation
      processes of the lowest excited states to be clarified. In the case of the EE
      geometrical isomer, a conformer (or rotamer) re-equilibration, implying an
      adiabatic interconversion during the lifetime in the S(1) state, was found to be
      operative. The deactivation channels of the excited cis isomers (ZE and ZZ)
      markedly depend on the conformational geometry, which is responsible for the
      adiabatic (rotamer-specific) cis --> trans photoisomerization. The radiative and
      radiationless relaxation rate parameters of the isomers and conformers of 1,2
      DSB, derived from the experimental and calculation results, allowed a complete
      and reasonably quantitative description of their behavior in the S(1) state.

PMID- 19575539
TI  - Identification of spectroscopic patterns of CH...O H-bonds in proteins.
AB  - Ab initio calculations are used to identify characteristics of vibrational and
      NMR spectra that signal the involvement of a protein backbone in a CH...O H-bond
      and that distinguish this sort of interaction from other H-bonds in which a
      protein might participate. Glycine and alanine dipeptides, in both their C7 and
      C5 minimum-energy structures, are paired with formamide in a number of different
      H-bonding arrangements. The CH...O H-bond is characterized by a small contraction
      of the C-H bond length, along with a blue shift in its stretching frequency,
      accompanied by an intensification of this vibrational band. In the context of NMR
      spectra, the bridging CH proton's chemical shift is moved downfield by 1-2 ppm.
      The aforementioned features are not produced by other H-bonds in which the
      protein backbone might participate, such as NH proton donation or accepting a
      proton via the peptide C=O.

PMID- 19575540
TI  - Protein NMR chemical shift calculations based on the automated fragmentation
      QM/MM approach.
AB  - An automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM)
      approach has been developed to routinely calculate ab initio protein NMR chemical
      shielding constants. The AF-QM/MM method is linear-scaling and trivially
      parallel. A general fragmentation scheme is employed to generate each residue
      centric region which is treated by quantum mechanics, and the environmental
      electrostatic field is described with molecular mechanics. The AF-QM/MM method
      shows good agreement with standard self-consistent field (SCF) calculations of
      the NMR chemical shieldings for the mini-protein Trp cage. The root-mean-square
      errors (RMSEs) for 1H, 13C, and 15N NMR chemical shieldings are equal to or less
      than 0.09, 0.32, and 0.78 ppm, respectively, for all Hartree-Fock (HF) and
      density functional theory (DFT) calculations reported in this work. The
      environmental electrostatic potential is necessary to accurately reproduce the
      NMR chemical shieldings using the AF-QM/MM approach. The point-charge models
      provided by AMBER, AM1/CM2, PM3/CM1, and PM3/CM2 all effectively model the
      electrostatic field. The latter three point-charge models are generated via
      semiempirical linear-scaling SCF calculations of the entire protein system. The
      correlations between experimental 1H NMR chemical shifts and theoretical
      predictions are >0.95 for AF-QM/MM calculations using B3LYP with the 6-31G**, 6
      311G**, and 6-311++G** basis sets. Our study, not unexpectedly, finds that
      conformational changes within a protein structure play an important role in the
      accurate prediction of experimental NMR chemical shifts from theory.

PMID- 19575541
TI  - Head glands of Monogenoidea: morphology, functionality, and potentialities in
      industrial production of surgery bioadhesives.
AB  - A review of the structure and functionality of monogenoidean head glands is
      provided. The unique features of the biochemical methods used by parasites to
      attach to, or detach from, fish hosts are highlighted. The potential use of
      monogenoidean cephalic secretions in the surgical field, and particularly in the
      production of bioadhesives, is suggested and critically supported by comparison
      with other available hemostatic agents.

PMID- 19575542
TI  - New data on Henneguya pellis (Myxozoa: Myxobolidae), a parasite of blue catfish
      Ictalurus furcatus.
AB  - The original description of Henneguya pellis, a myxozoan parasitizing blue
      catfish Ictalurus furcatus, is supplemented with new data on histopathology,
      spore morphology, and 18S small subunit (SSU) ribosomal DNA (rDNA) sequence.
      Plasmodia presented as both internal and external, raised, cyst-like lesions on
      the body wall of the peritoneal cavity and on the skin. The cysts contained
      numerous elongate, lanceolate myxospores, flattened parallel to the suture line.
      The spore body was 14.8 +/- 1.1 um (range 13.0-17.1) long and 4.8 +/- 0.8 um
      (range 4.0-7.4) wide in frontal view. The caudal appendages were 77.7 +/- 8.8
      (range 57.4-96.4) in length. There were 2 pyriform polar capsules, unequal in
      length, with the longer capsule measuring 7.2 +/- 0.6 um (range 6.2-8.4) in
      length and the shorter capsule measuring 6.5 +/- 0.5 um (range 5.5-8.0). The
      polar capsules were not significantly different in width, measuring 1.7 +/- 0.2
      um (range 1.4-1.9). There were 8 turns in the polar filament coil. The total
      length of the spore was 92.5 +/- 9.2 um (range 73.3-113.5). Spore morphology and
      site of development are similar to that of Henneguya sutherlandi from channel
      catfish; however, 18S rDNA sequence data support previous findings that identify
      H. pellis and H. sutherlandi as 2 distinct species.

PMID- 19575543
TI  - Parasitological and molecular features of the Hepatozoon species in the
      myocardium of Japanese Martens (Martes melampus melampus).
AB  - The Hepatozoon species in the myocardium of Japanese martens (Martes melampus
      melampus) was characterized by histological and molecular methods.
      Histologically, granulomatous nodules with Hepatozoon sp. merozoites/gametocytes,
      or schizonts, or both were observed in the hearts of Japanese martens. The most
      frequently observed forms were merozoites/gametocytes within phagocytes; each
      host cell included a zoite, which was not microscopically identifiable as a
      merozoite or gametocyte. Schizonts were oval in shape and 36.9 +/- 5.7 x 28.9 +/-
      3.4 MUm in size; each schizont had approximately 20-60 nuclei. The size of the
      merozoites could not be measured because no mature schizonts were observed. In
      the analyses of the partial 18S rRNA gene sequence, it was strongly suggested
      that the Hepatozoon sp. in Japanese marten and the Hepatozoon sp. in pine marten
      (Martes martes) in Scotland were the same species.

PMID- 19575546
TI  - Clinical significance of anti-cyclic citrullinated peptide antibodies in Egyptian
      patients with chronic hepatitis C virus genotype IV infection.
AB  - BACKGROUND: Symmetric polyarthritis associated with hepatitis C virus (HCV)
      infection frequently displays a clinical picture like rheumatoid arthritis (RA).
      Antibodies to cyclic citrullinated peptide (CCP) have high specificity for the
      diagnosis of RA. This study examined the frequency and clinical significance of
      anti-CCP antibodies in patients with chronic HCV infection, with and without
      manifestations of joint involvement, compared to RA patients. METHODS: Serum anti
      CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA
      and 47 patients with chronic HCV infection. Of those with HCV infection, 20
      patients had chronic HCV infection associated with articular involvement and 27
      patients had chronic HCV infection without any articular involvement. RESULTS:
      Anti-CCP antibody level was positive in 70% of RA patients, 8.5% of HCV-infected
      patients, and in 20% of HCV patients with articular manifestations. RF was
      positive in 76% of RA patients and in 60% of HCV patients with articular
      involvement. Cryoglobulins were found in 29% of HCV-infected patients and in 16%
      of RA patients. Cryoglobulins were more frequent among HCV patients with
      articular affection (35%) compared to HCV patients without articular affection
      (26%). CONCLUSIONS: Although anti-CCP antibodies remain a useful diagnostic tool
      for RA, their interpretation in HCV-infected patients with arthritis should be
      applied with caution. The possibility that those patients could be prone to
      develop RA cannot be ruled out. Those patients need careful clinical and
      radiological follow-up. Further large-scale studies are warranted.

PMID- 19575547
TI  - Is serum gamma-glutamyltransferase an exposure marker of xenobiotics? Empirical
      evidence with polycylic aromatic hydrocarbon.
AB  - BACKGROUND: We recently hypothesized that serum gamma-glutamyltransferase (GGT),
      within its reference range, predicts many diseases as a biomarker for background
      exposure to various xenobiotics. Even though normal serum GGT was associated with
      xenobiotics having very long half-lives (heavy metals, dioxin, or organochlorine
      pesticides), it was unknown whether GGT was associated with xenobiotics with
      short half-lives, including polycyclic aromatic hydrocarbons (PAHs), well known
      carcinogens. METHODS: Among 1256 adult participants in the National Health and
      Nutrition Examination Survey (NHANES) 2003-2004, urinary metabolites of PAH
      (monohydroxy-PAH), and serum GGT were measured. We selected the 10 monohydroxy
      PAHs (OH-PAHs) for which at least 90% of participants had concentrations greater
      than the limit of detection. RESULTS: Among the 10 OH-PAHs, eight had significant
      positive correlations with serum GGT. These correlations were similarly observed
      in men and women, and in individuals under 60 years of age. Unlike serum GGT,
      alanine aminotransferase, another liver enzyme, was not associated with OH-PAHs.
      CONCLUSIONS: Taken together with the previous epidemiological evidence, the
      associations of serum GGT with OH-PAHs reinforce the concept that serum GGT is a
      marker for various environmental pollutants encountered at background levels in
      the general population.

PMID- 19575549
TI  - Hyperleukocytosis: pseudohyperkalaemia and other biochemical abnormalities in
      hyperleukocytosis.

PMID- 19575548
TI  - Gender difference and determinants of C-reactive protein level in Korean adults.
AB  - BACKGROUND: C-reactive protein (CRP) has emerged as an important predictor for
      cardiovascular disease (CVD). To facilitate clinical and public health
      interventions, CRP thresholds have been defined as follows: low-risk (<1.0 mg/L),
      average-risk (1.0-3.0 mg/L), and high-risk (>3.0 mg/L). However, these cut-off
      thresholds are based on distributions in Western populations, and do not
      distinguish between men and women. METHODS: We examined CRP distribution, gender
      difference, and determinants of CRP concentrations ranging from 0.02 mg/L to 10.0
      mg/L, in 4923 Korean adults (2248 men; 2675 women) who received health checkups
      at Gangnam Severance Hospital from March 2006 to May 2007. RESULTS: The
      distribution of CRP was highly skewed toward lower concentrations. CRP was higher
      in men than women, and the cut-off thresholds for the high-risk tertile of CRP
      concentrations corresponded to 1.01 mg/L in men and 0.62 mg/L in women, based on
      the current study population. Age, male gender, cigarette smoking, physical
      activity, body mass index, total cholesterol, high density lipoprotein
      cholesterol, gamma-glutamyltransferase, and uric acid were independently
      associated with CRP concentrations. CONCLUSIONS: CRP distribution and gender
      difference in Korean adults were found to be different from previous Western
      studies, although similar risk factors influence CRP concentrations. Our results
      suggest that ethnicity and gender specific cut-off thresholds for CRP
      concentrations should be taken into consideration in CVD risk assessment.

PMID- 19575550
TI  - Review of the prevalence of macroprolactinaemia in a South African hospital.

PMID- 19575551
TI  - A novel aberrant form of e13a2 BCR-ABL1 transcript in chronic myelogenous
      leukemia undetectable with the standardized real-time quantitative polymerase
      chain reaction from the Europe Against Cancer Program.

PMID- 19575552
TI  - Positive correlations between serum and plasma matrix metalloproteinase (MMP)-2
      or MMP-9 levels in disease conditions.

PMID- 19575553
TI  - Doubt on prevention of false-positive results of cardiac troponin I by
      recentrifugation.

PMID- 19575554
TI  - Plasmalogens as a marker of elevated systemic oxidative stress in Parkinson's
      disease.

PMID- 19575555
TI  - A life with acetogens, thermophiles, and cellulolytic anaerobes.
AB  - Frankly, I was surprised to receive an invitation to write a prefatory chapter
      for the Annual Review of Microbiology. I have read several such chapters written
      by outstanding researchers, many of whom I know and admire. I did not think I
      belonged to such a preeminent group. In my view, my contributions to the
      physiology and biochemistry of anaerobic thermophilic bacteria and, more lately,
      to anaerobic fungi are modest compared to the contribution made by other authors
      of prefatory chapters. I am honored to write about my life and my work, and I
      hope that those who read this chapter will sense how exciting and rewarding they
      have been.

PMID- 19575556
TI  - How sweet it is! Cell wall biogenesis and polysaccharide capsule formation in
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a pathogenic fungus responsible for severe
      opportunistic infections. The most prominent feature of this yeast is its
      elaborate polysaccharide capsule, a complex structure that is required for
      virulence. The capsule is intimately associated with the cell wall, which
      underlies the capsule and offers the organism strength and flexibility in
      potentially hostile environments. Both structures are primarily composed of
      polysaccharides, offering a glimpse of the tremendous variation inherent in
      natural carbohydrate structures and their multiple biological functions. The
      steps in cell wall and capsule biosynthesis and assembly pose fascinating
      questions of metabolism, enzymology, cell biology, and regulation; the answers
      have potential application to treatment of a deadly infection. This article
      reviews current knowledge of cryptococcal cell wall and capsule biosynthesis and
      outstanding questions for the future.

PMID- 19575557
TI  - Genomics, genetics, and cell biology of magnetosome formation.
AB  - Magnetosomes are specialized organelles for magnetic navigation that comprise
      membrane-enveloped, nano-sized crystals of a magnetic iron mineral; they are
      formed by a diverse group of magnetotactic bacteria (MTB). The synthesis of
      magnetosomes involves strict genetic control over intracellular differentiation,
      biomineralization, and their assembly into highly ordered chains. Physicochemical
      control over biomineralization is achieved by compartmentalization within
      vesicles of the magnetosome membrane, which is a phospholipid bilayer associated
      with a specific set of proteins that have known or suspected functions in vesicle
      formation, iron transport, control of crystallization, and arrangement of
      magnetite particles. Magnetosome formation is genetically complex, and relevant
      genes are predominantly located in several operons within a conserved genomic
      magnetosome island that has been likely transferred horizontally and subsequently
      adapted between diverse MTB during evolution. This review summarizes the recent
      progress in our understanding of magnetobacterial cell biology, genomics, and the
      genetic control of magnetosome formation and magnetotaxis.

PMID- 19575558
TI  - Plant-growth-promoting rhizobacteria.
AB  - Several microbes promote plant growth, and many microbial products that stimulate
      plant growth have been marketed. In this review we restrict ourselves to bacteria
      that are derived from and exert this effect on the root. Such bacteria are
      generally designated as PGPR (plant-growth-promoting rhizobacteria). The
      beneficial effects of these rhizobacteria on plant growth can be direct or
      indirect. This review begins with describing the conditions under which bacteria
      live in the rhizosphere. To exert their beneficial effects, bacteria usually must
      colonize the root surface efficiently. Therefore, bacterial traits required for
      root colonization are subsequently described. Finally, several mechanisms by
      which microbes can act beneficially on plant growth are described. Examples of
      direct plant growth promotion that are discussed include (a) biofertilization,
      (b) stimulation of root growth, (c) rhizoremediation, and (d) plant stress
      control. Mechanisms of biological control by which rhizobacteria can promote
      plant growth indirectly, i.e., by reducing the level of disease, include
      antibiosis, induction of systemic resistance, and competition for nutrients and
      niches.

PMID- 19575559
TI  - Photorhabdus and a host of hosts.
AB  - Photorhabdus is a member of the family Enterobacteriaceae that lives in a
      mutualistic association with a Heterorhabditis nematode worm. The nematode worm
      burrows into insect prey and regurgitates Photorhabdus, which goes on to kill the
      insect. The nematode feeds off the growing bacteria until the insect tissues are
      exhausted, whereupon they reassociate and leave the cadaver in search of new
      prey. This highly efficient partnership has been used for many years as a
      biological crop protection agent. The dual nature of Photorhabdus as a pathogen
      and mutualist makes it a superb model for understanding these apparently
      exclusive activities. Furthermore, recently identified clinical isolates of
      Photorhabdus are helping us to understand how human pathogens can emerge from the
      enormous reservoir of invertebrate pathogens in the environment. As Photorhabdus
      has never been found outside a host animal, its niche represents an entirely
      biotic landscape. In this review we discuss what molecular adaptations allow this
      bacterium to complete this fascinating and complex life cycle.

PMID- 19575560
TI  - Global emergence of Batrachochytrium dendrobatidis and amphibian chytridiomycosis
      in space, time, and host.
AB  - Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that causes
      chytridiomycosis in amphibians. Only named in 1999, Bd is a proximate driver of
      declines in global amphibian biodiversity. The pathogen infects over 350 species
      of amphibians and is found on all continents except Antarctica. However, the
      processes that have led to the global distribution of Bd and the occurrence of
      chytridiomycosis remain unclear. This review explores the molecular,
      epidemiological, and ecological evidence that Bd evolved from an endemic
      ancestral lineage to achieve global prominence via anthropogenically mediated
      spread. We then consider the major host and pathogen factors that have led to the
      occurrence of chytridiomycosis in amphibian species, populations, and
      communities.

PMID- 19575561
TI  - Mitochondrial evolution and functions in malaria parasites.
AB  - Mitochondria in malaria parasites have some unusual evolutionary and functional
      features. The drastic reduction in the size of their mitochondrial genome,
      encoding just three proteins, appears to have originated at the point of
      divergence of dinoflagellates and apicomplexan parasites from ciliates and may
      have accompanied the acquisition of plastids by the former. Unusual translational
      machinery as revealed by the highly fragmented mitochondrial ribosomal RNA genes
      also appears to have originated at this deflection point. Some of the biochemical
      properties of malarial mitochondria also appear to be unconventional. Although
      tricarboxylic acid cycle enzymes are encoded by the genome, they do not appear to
      be involved in the full oxidation of glucose to fuel mitochondrial ATP synthesis
      in the blood stages of malaria parasites. A critical role of the mitochondrial
      electron transport chain appears to be to serve pyrimidine biosynthesis. In spite
      of their minimal nature, Plasmodium mitochondria are attractive targets for
      antimalarial drugs.

PMID- 19575564
TI  - Microbiology of the atmosphere-rock interface: how biological interactions and
      physical stresses modulate a sophisticated microbial ecosystem.
AB  - Life at the atmosphere-lithosphere boundary is an ancient terrestrial niche that
      is sparsely covered by thin subaerial biofilms. The microbial inhabitants of
      these biofilms (a) have adapted to all types of terrestrial/subaerial stresses
      (e.g., desiccation, extreme temperatures, low nutrient availability, intense
      solar radiation), (b) interact with minerals that serve as both a dwelling and a
      source of mineral nutrients, and (c) provoke weathering of rocks and soil
      formation. Subaerial communities comprise heterotrophic and phototrophic
      microorganisms that support each other's lifestyle. Major lineages of eubacteria
      associated with the early colonization of land (e.g., Actinobacteria,
      Cyanobacteria) are present in these habitats along with eukaryotes such as
      microscopic green algae and ascomycetous fungi. The subaerial biofilm inhabitants
      have adapted to desiccation, solar radiation, and other environmental challenges
      by developing protective, melanized cell walls, assuming microcolonial
      architectures and symbiotic lifestyles. How these changes occurred, their
      significance in soil formation, and their potential as markers of climate change
      are discussed below.

PMID- 19575565
TI  - Gene transfer and diversification of microbial eukaryotes.
AB  - The importance of lateral gene transfer in genome evolution of microbial
      eukaryotes is slowly being appreciated. Acquisitions of genes have led to
      metabolic adaptation in diverse eukaryotic lineages. In most cases the metabolic
      genes have originated from prokaryotes, often followed by sequential transfers
      between eukaryotes. However, the knowledge of gene transfer in eukaryotes is
      still mainly based on anecdotal evidence. Some of the observed patterns may be
      biases in experimental approaches and sequence databases rather than evolutionary
      trends. Rigorous systematic studies of gene acquisitions that allow for the
      possibility of exchanges of all categories of genes from all sources are needed
      to get a more objective view of gene transfer in eukaryote evolution. It may be
      that the role of gene transfer in the diversification process of microbial
      eukaryotes currently is underestimated.

PMID- 19575562
TI  - The Trypanosoma brucei flagellum: moving parasites in new directions.
AB  - African trypanosomes are devastating human and animal pathogens. Trypanosoma
      brucei rhodesiense and T. b. gambiense subspecies cause the fatal human disease
      known as African sleeping sickness. It is estimated that several hundred thousand
      new infections occur annually and the disease is fatal if untreated. T. brucei is
      transmitted by the tsetse fly and alternates between bloodstream-form and insect
      form life cycle stages that are adapted to survive in the mammalian host and the
      insect vector, respectively. The importance of the flagellum for parasite
      motility and attachment to the tsetse fly salivary gland epithelium has been
      appreciated for many years. Recent studies have revealed both conserved and novel
      features of T. brucei flagellum structure and composition, as well as surprising
      new functions that are outlined here. These discoveries are important from the
      standpoint of understanding trypanosome biology and identifying novel drug
      targets, as well as for advancing our understanding of fundamental aspects of
      eukaryotic flagellum structure and function.

PMID- 19575563
TI  - Malaria parasite development in the mosquito and infection of the mammalian host.
AB  - Plasmodium sporozoites are the product of a complex developmental process in the
      mosquito vector and are destined to infect the mammalian liver. Attention has
      been drawn to the mosquito stages and pre-erythrocytic stages owing to
      recognition that these are bottlenecks in the parasite life cycle and that
      intervention at these stages can block transmission and prevent infection.
      Parasite progression in the Anopheles mosquito, sporozoite transmission to the
      mammalian host by mosquito bite, and subsequent infection of the liver are
      characterized by extensive migration of invasive stages, cell invasion, and
      developmental changes. Preparation for the liver phase in the mammalian host
      begins in the mosquito with an extensive reprogramming of the sporozoite to
      support efficient infection and survival. Here, we discuss what is known about
      the molecular and cellular basis of the developmental progression of parasites
      and their interactions with host tissues in the mosquito and during the early
      phase of mammalian infection.

PMID- 19575566
TI  - Predatory lifestyle of Bdellovibrio bacteriovorus.
AB  - Bdellovibrio species are naturally predatory, small, motile, Deltaproteobacteria
      that invade the periplasm of other larger gram-negative bacteria, killing and
      digesting them. Bdellovibrio grows and divides inside the prey cell, in a
      structure called a bdelloplast, which then lyses, releasing the Bdellovibrio to
      prey upon more bacteria. This capability makes Bdellovibrio a potential
      therapeutic agent, but since its discovery in the 1960s it has not been applied
      in this way. This review considers what is known postgenomically about
      Bdellovibrio and its predatory lifestyle, drawing also from what was learned by
      the excellent microbial physiology work of the early Bdellovibrio researchers.
      Recent work on the diversity and evolution of predatory bdellovibrios, the role
      of surface structures in predation, and the ongoing questions about how
      Bdellovibrio switches between axenic and predatory growth and how its predatory
      activities may be tempered in the wild, as well as suggestions for future
      research priorities, are discussed.

PMID- 19575567
TI  - Sociobiology of the myxobacteria.
AB  - Cooperation is integral to much of biological life but can be threatened by
      selfish evolutionary strategies. Diverse cooperative traits have evolved among
      microbes, but particularly sophisticated forms of sociality have arisen in the
      myxobacteria, including group motility and multicellular fruiting body
      development. Myxobacterial cooperation has succeeded against socially destructive
      cheaters and can readily re-evolve from some socially defective genotypes.
      However, social harmony does not extend far. Spatially structured natural
      populations of the model species Myxococcus xanthus have fragmented into a large
      number of socially incompatible genotypes that exclude, exploit, and/or
      antagonize one another, including genetically similar neighbors. Here, we briefly
      review basic social evolution concepts as they pertain to microbes, discuss
      potential benefits of myxobacterial social traits, highlight recent empirical
      studies of social evolution in M. xanthus, and consider their implications for
      how myxobacterial cooperation and conflict evolve in the wild.

PMID- 19575568
TI  - Management of oxidative stress in Bacillus.
AB  - The spore-forming bacterium and model prokaryotic genetic system, Bacillus
      subtilis, is extremely useful in the study of oxidative stress management through
      proteomic and genome-wide transcriptomic analyses, as well as through detailed
      structural studies of the regulatory factors that govern the oxidative stress
      response. The factors that sense oxidants and induce expression of protective
      activities include the PerR and OhrR proteins, which show acute discrimination
      for their peroxide stimuli, whereas the general stress control factor, the RNA
      polymerase sigma(B) subunit and the thiol-based sensor Spx, govern the protective
      response to oxidants under multiple stress conditions. Some specific and some
      redundant protective mechanisms are mobilized at different stages of the Bacillus
      developmental cycle to deal with vulnerable cells in stationary-phase conditions
      and during spore germination and outgrowth. An important unknown is the nature
      and influence of the low-molecular-weight thiols that mediate the buffering of
      the redox environment.

PMID- 19575569
TI  - Probiotic and gut lactobacilli and bifidobacteria: molecular approaches to study
      diversity and activity.
AB  - Lactobacilli and bifidobacteria have traditionally been recognized as potential
      health-promoting microbes in the human gastrointestinal tract, which is clearly
      reflected by the pre- and probiotic supplements on the market. Bacterial genomics
      of lactobacilli and bifidobacteria is initiating the identification and
      validation of specific effector molecules that mediate host health effects.
      Combined with advanced postgenomic mammalian host response analyses, elucidations
      of the molecular interactions and mechanisms that underlie the host-health
      effects observed are beginning to be gathered. These developments should be seen
      in the complexity of the microbiota-host relationships in the intestine, which
      through the new metagenomic era has regained momentum and will undoubtedly
      progress to functional microbiomics and host response analyses within the next
      decade. Taken together, these developments are anticipated to dramatically alter
      the scope and impact of the probiotic field, offering tremendous new
      opportunities with accompanying challenges for research and industrial
      application.

PMID- 19575570
TI  - Role of GTPases in bacterial ribosome assembly.
AB  - The assembly of the ribosome, a complex molecular machine composed of RNA and
      protein, is a poorly understood process. Recent work has demonstrated that
      GTPases are likely to play key roles in the assembly of ribosomes in bacteria and
      eukaryotes. This review highlights several bacterial ribosome assembly GTPases
      (RA-GTPases) and discusses possible functions for these proteins in the
      biogenesis of individual ribosomal subunits and subunit joining. RA-GTPases
      appear to link various aspects of the cell cycle and metabolism with translation.
      How these RA-GTPases may coordinate these connections are discussed.

PMID- 19575572
TI  - Anaerobic oxidation of methane: progress with an unknown process.
AB  - Methane is the most abundant hydrocarbon in the atmosphere, and it is an
      important greenhouse gas, which has so far contributed an estimated 20% of
      postindustrial global warming. A great deal of biogeochemical research has
      focused on the causes and effects of the variation in global fluxes of methane
      throughout earth's history, but the underlying microbial processes and their key
      agents remain poorly understood. This is a disturbing knowledge gap because 85%
      of the annual global methane production and about 60% of its consumption are
      based on microbial processes. Only three key functional groups of microorganisms
      of limited diversity regulate the fluxes of methane on earth, namely the aerobic
      methanotrophic bacteria, the methanogenic archaea, and their close relatives, the
      anaerobic methanotrophic archaea (ANME). The ANME represent special lines of
      descent within the Euryarchaeota and appear to gain energy exclusively from the
      anaerobic oxidation of methane (AOM), with sulfate as the final electron acceptor
      according to the net reaction: CH(4) + SO(42-) ---> HCO(3-) + HS(-) + H(2)O. This
      review summarizes what is known and unknown about AOM on earth and its key
      catalysts, the ANME clades and their bacterial partners.

PMID- 19575571
TI  - Biological insights from structures of two-component proteins.
AB  - Two-component signal transduction based on phosphotransfer from a histidine
      protein kinase to a response regulator protein is a prevalent strategy for
      coupling environmental stimuli to adaptive responses in bacteria. In both
      histidine kinases and response regulators, modular domains with conserved
      structures and biochemical activities adopt different conformational states in
      the presence of stimuli or upon phosphorylation, enabling a diverse array of
      regulatory mechanisms based on inhibitory and/or activating protein-protein
      interactions imparted by different domain arrangements. This review summarizes
      some of the recent structural work that has provided insight into the functioning
      of bacterial histidine kinases and response regulators. Particular emphasis is
      placed on identifying features that are expected to be conserved among different
      two-component proteins from those that are expected to differ, with the goal of
      defining the extent to which knowledge of previously characterized two-component
      proteins can be applied to newly discovered systems.

PMID- 19575574
TI  - Magnetic source imaging for the surgical evaluation of electroencephalography
      confirmed secondary bilateral synchrony in intractable epilepsy.
AB  - OBJECT: Routine scalp electroencephalography (EEG) cannot always distinguish
      whether generalized epileptiform discharges are the result of primary bilateral
      synchrony or secondary bilateral synchrony (SBS) from a focal origin; this is an
      important distinction because the latter may be amenable to resection. Whole-head
      magnetoencephalography (MEG) has superior spatial resolution compared with
      traditional EEG, and can potentially elucidate seizure foci in challenging
      epilepsy cases in which patients are undergoing evaluation for surgery. METHODS:
      Sixteen patients with medically intractable epilepsy in whom SBS was suspected
      were referred for magnetic source (MS) imaging. All patients had bilateral,
      synchronous, widespread, and most often generalized spike-wave discharges on
      scalp EEG studies, plus some other clinical (for example, seizure semiology) or
      MR imaging feature (for example, focal lesion) suggesting focal onset and hence
      possible surgical candidacy. The MS imaging modality is the combination of whole
      head MEG and parametric reconstruction of corresponding electrical brain sources.
      An MEG and simultaneous EEG studies were recorded with a 275-channel whole-head
      system. Single-equivalent current dipoles were estimated from the MEG data, and
      dipole locations and orientations were superimposed on patients' MR images.
      RESULTS: The MS imaging studies revealed focal dipole clusters in 12 (75%) of the
      16 patients, of which a single dipole cluster was identified in 7 patients (44%).
      Patient age, seizure type, duration of disease, video-EEG telemetry, and MR
      imaging results were analyzed to determine factors predictive of having clusters
      revealed on MS imaging. Of these factors, only focal MR imaging anatomical
      abnormalities were associated with dipole clusters (chi-square test, p = 0.03).
      Selective resections (including the dipole cluster) in 7 (87%) of 8 patients
      resulted in seizure-free or rare seizure outcomes (Engel Classes I and II).
      CONCLUSIONS: Magnetic source imaging may provide noninvasive anatomical and
      neurophysiological confirmation of localization in patients in whom there is a
      suspicion of SBS (based on clinical or MR imaging data), especially in those with
      an anatomical lesion. Identification of a focal seizure origin has significant
      implications for both resective and nonresective treatment of intractable
      epilepsy.

PMID- 19575575
TI  - The selective amygdalohippocampectomy for intractable temporal limbic seizures.
AB  - OBJECT: The proximal (anterior) transsylvian approach through a pterional
      craniotomy was developed by the senior author (M.G.Y.) in 1967 for the
      microsurgical treatment of saccular aneurysms of the circle of Willis,
      frontoorbital and temporobasal arteriovenous malformations, cavernomas, and
      extrinsic and intrinsic tumors. The acquired positive surgical experiences on
      this large series enabled the senior author, in 1973, to apply this approach for
      the selective amygdalohippocampectomy in patients with intractable mesial
      temporal lobe epilepsy. METHODS: The proximal (anterior) transsylvian
      transamygdala approach to the mesial temporal structures permits the selective
      two-thirds resection of the amygdala and hippocampus-parahippocampus in an
      anteroinferior to posteroinferior exploration axis along the base of the
      semicircular temporal horn. This strategy ensures preservation of the overlying
      neopallial temporal convolutions such as the T1, T2, T3, and T4 gyri as well as
      the related subcortical connective fiber systems and other essential components
      of the temporal white matter. The application of rigid brain self-retaining
      retractor systems was strictly avoided during the entire procedure. Computer
      assisted navigation was never used. On routine postoperative CT scanning and MR
      imaging studies, infarction was not observed in any patient. The availability of
      tractography technology has proven that the connective fiber system around the
      resected mesial temporal area remains intact. RESULTS: The surgical outcome and
      results on neoplastic and vascular lesions of the mesiobasal temporal region have
      been presented in Volumes II, IIIB, and IVB of Microneurosurgery. The surgical
      outcomes and results in 102 patients with mesial temporal seizures who underwent
      surgery performed by the senior author in Zurich have been previously published.
      In this paper, 73 patients who underwent surgery between 1994 and September 2006
      in Little Rock, Arkansas, are presented, and 13 other patients are excluded who
      underwent surgery after September 2006. Altogether, among 188 patients who
      underwent surgery, there was no surgical mortality or morbidity, and no
      neurological deficits, new neurocognitive dysfunction, or impairments of the
      preoperative incapacities. CONCLUSIONS: The surgical outcome in terms of seizures
      was rewarding in the majority of patients, particularly in those who exhibited
      the following irregularities on preoperative investigations: regular local
      dysfunctions on electroencephalography, dysmorphic changes in the mesiobasal
      temporal parenchyma on MR imaging studies, and hypometabolism in the anterior
      third of the temporal lobe on PET studies.

PMID- 19575576
TI  - The natural history of brain contusion: an analysis of radiological and clinical
      progression.
AB  - OBJECT: Although brain contusions are a common neurosurgical condition,
      surprisingly little has been written about their natural history. The purpose of
      this study was to identify factors that predict radiological and clinically
      significant progression of this pattern of traumatic brain injury in patients who
      did not initially require surgery. On the basis of their results and the
      available literature, the authors suggest a management algorithm. METHODS: The
      authors performed a retrospective review of clinical and radiological records of
      consecutive patients with brain contusions who initially underwent conservative
      treatment. Significant radiological progression was defined as a 30% increase in
      contusion size on CT scans. Statistical analysis was performed to identify
      clinical and radiological predictors of CT contusion progression, the
      significance of progression, and predictors of clinical outcome. RESULTS: Of 98
      patients identified with brain contusions who initially received conservative
      treatment, 44 (45%) had significant progression on CT, and 19 (19%) required
      surgical intervention. The initial size of the contusion and the presence of
      subdural hematoma were the only statistically significant predictors of CT
      progression in the multivariate analysis (p = 0.0212 and 0.05, respectively).
      Four patients required delayed contusion evacuation (3 had radiological
      progression on follow-up scans). Good Glasgow Coma Scale (GCS) scores on
      presentation and younger age were predictors of eventual discharge from the
      hospital (OR 1.471, CI 1.233-1.755, p < 0.001 and OR 0.949, CI 0.912-0.988, p =
      0.011, respectively). No patients with an initial GCS score of 15 or an initial
      contusion size < 14 ml required delayed evacuation. CONCLUSIONS: Contusion
      progression is a common phenomenon that is seen more commonly in larger
      contusions. Patients with large contusions and low initial GCS scores are at risk
      for delayed deterioration. A proposed management algorithm for patients with
      contusions initially treated conservatively may help practitioners identify the
      best course of treatment.

PMID- 19575577
TI  - Radiation-induced rhabdomyosarcoma of the brainstem in a patient with
      neurofibromatosis type 2.
AB  - Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder
      characterized by the development of benign tumors of the peripheral nervous
      system and the CNS, including schwannomas, meningiomas, and ependymomas. The gene
      responsible for the development of NF2 acts as a tumor suppressor gene.
      Stereotactic radiotherapy (SRT) or single-fraction stereotactic radiosurgery has
      been increasingly used in the past decades to treat benign tumors in patients
      with NF2. These radiotherapy methods are less invasive and can be potentially
      used to treat multiple tumors in a single session. The risk of inducing
      malignancy is unclear. Few reports exist of malignant peripheral nerve sheath
      tumors, meningiomas, or ependymomas occurring after SRT or stereotactic
      radiosurgery in patients with NF2. The authors present the first documented case
      of rhabdomyosarcoma following SRT for multiple NF2-associated schwannomas.
      Compared with patients with sporadic tumors, NF2 patients having a germline tumor
      suppressor gene defect may be more prone to secondary malignancies after
      treatment involving radiation therapy.

PMID- 19575578
TI  - My journey from horticulture to plant biology.
AB  - The author describes the circumstances and opportunities that led him to higher
      education and to pursue a research career in plant biology. He acknowledges the
      important roles a few individuals played in guiding him in his career. His early
      work on flowering was followed by studies on the physiological roles and the
      metabolism of gibberellins and abscisic acid. He describes how collaborations and
      technical developments advanced his research from measuring hormones by bioassay
      to their identification and quantification by mass spectrometry and cloning of
      hormone biosynthetic genes.

PMID- 19575579
TI  - Roles of proteolysis in plant self-incompatibility.
AB  - Self-incompatibility (SI) is a genetically controlled system adopted by many
      flowering plants to avoid inbreeding and thus to maintain species diversity.
      Generally, self-pollen rejection occurs through active pollen and pistil
      recognition and subsequent signaling responses. So far, three different molecular
      controls of pollen and pistil recognition have been characterized and are
      exemplified by three families: the Solanaceae, the Papaveraceae, and the
      Brassicaceae. With more components involved in these SI systems coming to light,
      recent studies have provided intriguing insights into the downstream reactions
      that follow the initial SI signal perception. The process of pollen rejection is
      closely associated with rapid and effective proteolytic events, including the
      ubiquitin-proteasome pathway and the vacuolar sorting pathway. Here, we review
      our current understanding of the roles of proteolysis in SI responses of
      flowering plants.

PMID- 19575580
TI  - 14-3-3 and FHA domains mediate phosphoprotein interactions.
AB  - Many aspects of plant growth and development require specific protein
      interactions to carry out biochemical and cellular functions. Several proteins
      mediate these interactions, two of which specifically recognize phosphoproteins:
      14-3-3 proteins and proteins with FHA domains. These are the only phosphobinding
      domains identified in plants. Both domains are present in animals and plants, and
      are used by plant proteins to regulate metabolic, developmental, and signaling
      pathways. 14-3-3s regulate sugar metabolism, proton gradients, and control
      transcription factor localization. FHA domains are modular domains often found in
      multidomain proteins that are involved in signal transduction and plant
      development.

PMID- 19575581
TI  - Selaginella and 400 million years of separation.
AB  - Selaginella (spikemoss) is an enigma in the plant kingdom. Although a fascination
      to botanists at the turn of the twentieth century, members of this genus are
      unremarkable in appearance, never flower, and are of no agronomic value. However,
      members of this genus are relicts from ancient times, and one has to marvel at
      how this genus has survived virtually unchanged in appearance for hundreds of
      millions of years. In light of the recent completion of the Selaginella
      moellendorffii genome sequence, this review is intended to survey what is known
      about Selaginella, with a special emphasis on recent inquiries into its unique
      biology and importance in understanding the early evolution of vascular plants.

PMID- 19575582
TI  - Sensing and responding to excess light.
AB  - Plants and algae often absorb too much light-more than they can actually use in
      photosynthesis. To prevent photo-oxidative damage and to acclimate to changes in
      their environment, photosynthetic organisms have evolved direct and indirect
      mechanisms for sensing and responding to excess light. Photoreceptors such as
      phototropin, neochrome, and cryptochrome can sense excess light directly and
      relay signals for chloroplast movement and gene expression responses. Indirect
      sensing of excess light through biochemical and metabolic signals can be
      transduced into local responses within chloroplasts, into changes in nuclear gene
      expression via retrograde signaling pathways, or even into systemic responses,
      all of which are associated with photoacclimation.

PMID- 19575583
TI  - Aquilegia: a new model for plant development, ecology, and evolution.
AB  - The lower eudicot genus Aquilegia holds enormous potential for investigating
      aspects of development, ecology, and evolution that are otherwise unrepresented
      among existing model systems. Its evolutionary history is of particular interest
      because it represents a phylogenetic midpoint between models such as Arabidopsis
      and Oryza but, at the same time, has experienced a recent adaptive radiation
      within the genus. To take advantage of these features, a collaborative group has
      developed a number of genetic and genomic resources for Aquilegia that have
      facilitated the study of its distinct morphology. This work has demonstrated that
      although the petaloid sepals of Aquilegia do not depend on B-class genes for
      their identity, these loci do control development of the petals, stamens, and
      novel staminodium. Overall, Aquilegia stands as a key example of the potential
      utility and speed of developing new genetic model systems.

PMID- 19575584
TI  - Environmental effects on spatial and temporal patterns of leaf and root growth.
AB  - Leaves and roots live in dramatically different habitats, but are parts of the
      same organism. Automated image processing of time-lapse records of these organs
      has led to understanding of spatial and temporal patterns of growth on time
      scales from minutes to weeks. Growth zones in roots and leaves show distinct
      patterns during a diel cycle (24 h period). In dicot leaves under nonstressful
      conditions these patterns are characterized by endogenous rhythms, sometimes
      superimposed upon morphogenesis driven by environmental variation. In roots and
      monocot leaves the growth patterns depend more strongly on environmental
      fluctuations. Because the impact of spatial variations and temporal fluctuations
      of above- and belowground environmental parameters must be processed by the plant
      body as an entire system whose individual modules interact on different levels,
      growth reactions of individual modules are often highly nonlinear. A mechanistic
      understanding of plant resource use efficiency and performance in a dynamically
      fluctuating environment therefore requires an accurate analysis of leaf and root
      growth patterns in conjunction with knowledge of major intraplant communication
      systems and metabolic pathways.

PMID- 19575585
TI  - Short-read sequencing technologies for transcriptional analyses.
AB  - The technological advances in DNA sequencing over the past five years have
      changed our approaches to gene expression analysis, fundamentally altering the
      basic methods used and in most cases driving a shift from hybridization-based
      approaches to sequencing-based approaches. Quantitative, tag-based studies of
      gene expression were one of the earliest applications of these next-generation
      technologies, but the tremendous depth of sequencing facilitates de novo
      transcript discovery, which replaces traditional expressed sequence tag (EST)
      sequencing. In addition, these technologies have created new opportunities for
      understanding the generation, stability, and decay of RNA and the impacts of
      chromatin differences on gene expression. As we review the impact of these
      methods on plant biology, we also mention published studies from animal systems
      when the methods are broadly applicable. We can anticipate that the published
      work over the past few years is a harbinger of much broader studies that are yet
      to be published and are sure to further advance our understanding of plant
      genomes in a field changing at a dizzying pace.

PMID- 19575586
TI  - Biosynthesis of plant isoprenoids: perspectives for microbial engineering.
AB  - Isoprenoids are a large and highly diverse group of natural products with many
      functions in plant primary and secondary metabolism. Isoprenoids are synthesized
      from common prenyl diphosphate precursors through the action of terpene synthases
      and terpene-modifying enzymes such as cytochrome P450 monooxygenases. Many
      isoprenoids have important applications in areas such as human health and
      nutrition, and much effort has been directed toward their production in microbial
      hosts. However, many hurdles must be overcome in the elucidation and functional
      microbial expression of the genes responsible for biosynthesis of an isoprenoid
      of interest. Here, we review investigations into isoprenoid function and gene
      discovery in plants as well as the latest advances in isoprenoid pathway
      engineering in both plant and microbial hosts.

PMID- 19575587
TI  - The circadian system in higher plants.
AB  - The circadian clock regulates diverse aspects of plant growth and development and
      promotes plant fitness. Molecular identification of clock components, primarily
      in Arabidopsis, has led to recent rapid progress in our understanding of the
      clock mechanism in higher plants. Using mathematical modeling and experimental
      approaches, workers in the field have developed a model of the clock that
      incorporates both transcriptional and posttranscriptional regulation of clock
      genes. This cell-autonomous clock, or oscillator, generates rhythmic outputs that
      can be monitored at the cellular and whole-organism level. The clock not only
      confers daily rhythms in growth and metabolism, but also interacts with signaling
      pathways involved in plant responses to the environment. Future work will lead to
      a better understanding of how the clock and other signaling networks are
      integrated to provide plants with an adaptive advantage.

PMID- 19575588
TI  - Bias in plant gene content following different sorts of duplication: tandem,
      whole-genome, segmental, or by transposition.
AB  - Each mode of gene duplication (tandem, tetraploid, segmental, transpositional)
      retains genes in a biased manner. A reciprocal relationship exists between plant
      genes retained postpaleotetraploidy versus genes retained after an ancient tandem
      duplication. Among the models (C, neofunctionalization, balanced gene drive) and
      ideas that might explain this relationship, only balanced gene drive predicts
      reciprocity. The gene balance hypothesis explains that more "connected" genes--by
      protein-protein interactions in a heteromer, for example--are less likely to be
      retained as a tandem or transposed duplicate and are more likely to be retained
      postpaleotetraploidy; otherwise, selectively negative dosage effects are created.
      Biased duplicate retention is an instant and neutral by-product, a spandrel, of
      purifying selection. Balanced gene drive expanded plant gene families, including
      those encoding proteasomal proteins, protein kinases, motors, and transcription
      factors, with each paleotetraploidy, which could explain trends involving
      complexity. Balanced gene drive is a saltation mechanism in the mutationist
      tradition.

PMID- 19575589
TI  - Photorespiratory metabolism: genes, mutants, energetics, and redox signaling.
AB  - Photorespiration is a high-flux pathway that operates alongside carbon
      assimilation in C(3) plants. Because most higher plant species photosynthesize
      using only the C(3) pathway, photorespiration has a major impact on cellular
      metabolism, particularly under high light, high temperatures, and CO(2) or water
      deficits. Although the functions of photorespiration remain controversial, it is
      widely accepted that this pathway influences a wide range of processes from
      bioenergetics, photosystem II function, and carbon metabolism to nitrogen
      assimilation and respiration. Crucially, the photorespiratory pathway is a major
      source of H(2)O(2) in photosynthetic cells. Through H(2)O(2) production and
      pyridine nucleotide interactions, photorespiration makes a key contribution to
      cellular redox homeostasis. In so doing, it influences multiple signaling
      pathways, particularly those that govern plant hormonal responses controlling
      growth, environmental and defense responses, and programmed cell death. The
      potential influence of photorespiration on cell physiology and fate is thus
      complex and wide ranging. The genes, pathways, and signaling functions of
      photorespiration are considered here in the context of whole plant biology, with
      reference to future challenges and human interventions to diminish
      photorespiratory flux.

PMID- 19575590
TI  - The role of hybridization in plant speciation.
AB  - The importance of hybridization in plant speciation and evolution has been
      debated for decades, with opposing views of hybridization as either a creative
      evolutionary force or evolutionary noise. Hybrid speciation may occur at either
      the homoploid (i.e., between two species of the same ploidy) or the polyploid
      level, each with its attendant genetic and evolutionary consequences. Whereas
      allopolyploidy (i.e., resulting from hybridization and genome doubling) has long
      been recognized as an important mode of plant speciation, the implications of
      genome duplication have typically not been taken into account in most fields of
      plant biology. Recent developments in genomics are revolutionizing our views of
      angiosperm genomes, demonstrating that perhaps all angiosperms have likely
      undergone at least one round of polyploidization and that hybridization has been
      an important force in generating angiosperm species diversity. Hybridization and
      polyploid formation continue to generate species diversity, with several new
      allopolyploids having originated just within the past century or so. The origins
      of polyploid species-whether via hybridization between species or between
      genetically differentiated populations of a single species-and the immediate
      genetic consequences of polyploid formation are therefore receiving enthusiastic
      attention. The time is therefore right for a review of the role of hybridization
      in plant speciation.

PMID- 19575591
TI  - Modified chitosan derivative micelle system for natural anti-tumor product
      gambogic acid delivery.
AB  - A chitosan derivative micelle system was developed as the delivery system for a
      novel anti-tumor drug, gambogic acid (GA). The physicochemical and pharmaceutical
      properties of GA-loaded micelles (GA-M) were evaluated compared with the
      formulation GA-L-arginine (GA-L) injection, which entered phase I clinical
      trials. The results showed that GA-M had high GA-loading rate (29.8 +/- 0.17%),
      high entrapment efficiency (63.8 +/- 0.52%), and small particle size (108.2 +/-
      0.8 nm). After i.v. administration at the dose of 4 mg/kg, the area under
      concentration-time curve (AUC) and elimination half-life (T(1/2)beta) of GA-M
      were all increased by 1.7-fold compared with GA-L in rat. Biodistribution study
      indicated that approximately 67% of GA in the GA-M group was distributed in the
      liver, while the value of the GA-L group was approximately 55%. Additionally, GA
      amount in the kidney was greatly reduced in the GA-M group. Also, GA-M was shown
      to reduce the acute toxicity after i.v. administration in mice compared with GA
      L. The present study indicated that GA was rapidly eliminated from the blood and
      transferred to the tissues, especially the liver. Moreover, GA acute toxicity and
      irritation to vein were decreased.

PMID- 19575595
TI  - Navigating between the Scylla and Charybdis of prescribing dietary protein for
      chronic kidney diseases.
AB  - A fundamental clinical problem in treating patients with chronic kidney disease
      (CKD) is designing their diets: an excess of protein leads to the accumulation of
      uremic toxins, whereas a diet insufficient in protein could lead to loss of lean
      body mass. The benefits of dietary protein restriction include reducing the
      accumulation of metabolic waste products that can suppress appetite and stimulate
      muscle protein wasting. There also is a potential for slowing the loss of kidney
      function. Unfortunately, advanced CKD is strongly associated with a protein
      wasting syndrome that is directly correlated with morbidity and mortality.
      Fortunately, the mechanisms underlying negative responses to an excess of dietary
      protein, including the causes of the wasting syndrome, are beginning to be
      understood. We have examined how dietary protein influences the mechanisms
      causing protein wasting, and we propose a framework for approaching the variable
      dietary protein requirements in patients with CKD or end-stage kidney disease.

PMID- 19575597
TI  - Sialic acid is an essential nutrient for brain development and cognition.
AB  - The rapid growth of infant brains places an exceptionally high demand on the
      supply of nutrients from the diet, particularly for preterm infants. Sialic acid
      (Sia) is an essential component of brain gangliosides and the polysialic acid
      (polySia) chains that modify neural cell adhesion molecules (NCAM). Sia levels
      are high in human breast milk, predominately as N-acetylneuraminic acid (Neu5Ac).
      In contrast, infant formulas contain a low level of Sia consisting of both Neu5Ac
      and N-glycolylneuraminic acid (Neu5Gc). Neu5Gc is implicated in some human
      inflammatory diseases. Brain gangliosides and polysialylated NCAM play crucial
      roles in cell-to-cell interactions, neuronal outgrowth, modifying synaptic
      connectivity, and memory formation. In piglets, a diet rich in Sia increases the
      level of brain Sia and the expression of two learning-related genes and enhances
      learning and memory. The purpose of this review is to summarize the evidence
      showing the importance of dietary Sia as an essential nutrient for brain
      development and cognition.

PMID- 19575599
TI  - Nonalcoholic fatty liver disease and low-carbohydrate diets.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance,
      obesity, and other features of metabolic syndrome and is known to be the most
      common cause for abnormal liver enzymes. The recent surge in the number of
      patients with NAFLD has been accompanied by an increase in research on potential
      treatment options, particularly weight loss and dietary interventions. Given the
      growing interest on the role of carbohydrates in the prevention and treatment of
      NAFLD, this review discusses the relationship between the amount of carbohydrates
      in the diet and effects on NAFLD, with special emphasis on a low-carbohydrate
      diet. We discuss the role of insulin resistance in the pathophysiology of NAFLD
      and provide an overview of various popular diets and their role as a treatment
      option for NAFLD. Additional large, longer-duration trials studying the efficacy
      of a low-carbohydrate diet in the treatment and prevention of NAFLD are eagerly
      awaited.

PMID- 19575601
TI  - Is there glucose production outside of the liver and kidney?
AB  - This review analyzes the evidence presented to support the role of organs other
      than the liver and kidney to release substantial amounts of glucose into the
      mammalian blood circulation. The evidence includes (a) the identification of
      gluconeogenic enzyme activities in various organs, especially the small
      intestine, (b) levels of mRNA for the same enzymes, and (c) measurements of
      gluconeogenic flux in the small intestine. The latter would be the definite proof
      of extrahepatic, extrarenal glucose production. We critically evaluate the
      radioactive and stable isotopic techniques used to measure intestinal
      gluconeogenesis. We also simulate the impact of unavoidable measurement errors on
      apparent rates of intestinal gluconeogenesis. We conclude that there is so far no
      credible evidence to support the concept that glucose can be produced by the
      intestine or by muscle.

PMID- 19575602
TI  - Nutritional systems biology: definitions and approaches.
AB  - Nutrigenetics and nutrigenomics are nascent areas that are evolving quickly and
      riding on the wave of "personalized medicine" that is providing opportunities in
      the discovery and development of nutraceutical compounds. The human genome
      sequence and sequences of model organisms provide the equivalent of comprehensive
      blueprints and parts lists that describe dynamic networks and the bases for
      understanding their responses to external and internal perturbations. Unfolding
      the interrelationships among genes, gene products, and dietary habits is
      fundamental for identifying individuals who will benefit most from, or be placed
      at risk by, intervention strategies. More accurate assessment of the inputs to
      human health and the consequences of those inputs measured as accurate
      transcriptomic, proteomic, and metabolomic analyses would bring personalized
      health/diet to practice far faster than would waiting for a predictive knowledge
      of genetic variation. It is widely recognized that systems and network biology
      has the potential to increase our understanding of how nutrition influences
      metabolic pathways and homeostasis, how this regulation is disturbed in a diet
      related disease, and to what extent individual genotypes contribute to such
      diseases.

PMID- 19575603
TI  - Effects of arsenic on maternal and fetal health.
AB  - Arsenic, which is commonly found in drinking water, is a potent toxicant, but
      little is known about its effects on maternal health. Arsenic's modes of action
      include enzyme inhibition and oxidative stress as well as immune, endocrine, and
      epigenetic effects. A couple of studies reported increased blood pressure and
      anemia during pregnancy. Susceptibility to arsenic is dependent on the
      biomethylation, which occurs via one-carbon metabolism. Methylarsonic acid and
      dimethylarsinic acid are main metabolites in urine, and elevated methylarsonic
      acid is considered a general risk factor. Arsenic easily passes the placenta, and
      a few human studies indicate a moderately increased risk of impaired fetal growth
      and increased fetal and infant mortality. The fetus and infant are probably
      partly protected by the increased methylation of arsenic during pregnancy and
      lactation; the infant is also protected by low arsenic excretion in breast milk.
      Early-life exposure may induce changes that will become apparent much later in
      life.

PMID- 19575604
TI  - Metabolic interactions between prokinetic agents domperidone and erythromycin: an
      in vitro analysis.
AB  - This study examined in vitro interaction between domperidone and erythromycin.
      Both are prescribed for refractory gastroparesis. Domperidone is metabolized via
      human cytochrome P4503A4. Erythromycin is a CYP3A4 inhibitor. Incubations
      evaluated domperidone metabolite formation in human liver microsomes and
      recombinant CYP3A4. Concentration- and time-dependent inhibition of 500 microM
      domperidone was studied with 2.5-200 microM erythromycin over 10-40 min.
      Domperidone metabolite (5-hydroxy domperidone, M3) formation was inhibited by
      erythromycin in a concentration- and time-dependent manner. The K(I) estimate was
      18.4 microM in human liver microsomes and 4.1 microM in CYP3A4. Using a model
      incorporating CYP3A4 hepatic and gut inhibition, in vitro estimates from human
      liver microsomes and CYP3A4 were used to predict in vivo AUCi/AUC ratios of 2.54
      and 4.95, respectively. Significant inhibition of domperidone metabolism by
      erythromycin occurs. This predicts greater domperidone drug exposure when used
      with erythromycin. This important drug-drug interaction will be evaluated in
      future human studies.

PMID- 19575605
TI  - Evolving the capacity to understand actions, intentions, and goals.
AB  - We synthesize the contrasting predictions of motor simulation and teleological
      theories of action comprehension and present evidence from a series of studies
      showing that monkeys and apes-like humans-extract the meaning of an event by (a)
      going beyond the surface appearance of actions, attributing goals and intentions
      to the agent; (b) using details about the environment to infer when an action is
      rational or irrational; (c) making predictions about an agent's goal and the most
      probable action to obtain the goal, within the constraints of the situation; (d)
      predicting the most probable outcome of actions even when they are
      physiologically incapable of producing the actions; and (e) combining information
      about means and outcomes to make decisions about social interactions, some with
      moral relevance. These studies reveal the limitations of motor simulation
      theories, especially those that rely on the notion of direct matching and mirror
      neuron activation. They provide support, however, for a teleological theory,
      rooted in an inferential process that extracts information about action means,
      potential goals, and the environmental constraints that limit rational action.

PMID- 19575608
TI  - A bridge over troubled water: reconsolidation as a link between cognitive and
      neuroscientific memory research traditions.
AB  - There are two research traditions on dynamic memory processes. In cognitive
      psychology, the malleable nature of long-term memory has been extensively
      documented. Distortions, such as the misinformation effect or hindsight bias,
      illustrate that memories can be easily changed, often without their owner taking
      notice. On the other hand, effects like hypermnesia demonstrate that memory might
      be more reliable than these distortions suggest. In the neuroscience field,
      similar observations were obtained mostly from animal studies. Research on memory
      consolidation suggested that memories become progressively resistant to amnesic
      treatments over time, but the reconsolidation phenomenon showed that this
      stability can be transiently lifted when these memories are reactivated, i.e.,
      retrieved. Surprisingly, both research traditions have not taken much notice of
      each others' advances in understanding memory dynamics. We apply concepts
      developed in neuroscience to phenomena revealed in cognitive psychology to
      illustrate how these twins separated at birth may be reunited again.

PMID- 19575609
TI  - Creativity.
AB  - The psychological study of creativity is essential to human progress. If strides
      are to be made in the sciences, humanities, and arts, we must arrive at a far
      more detailed understanding of the creative process, its antecedents, and its
      inhibitors. This review, encompassing most subspecialties in the study of
      creativity and focusing on twenty-first-century literature, reveals both a
      growing interest in creativity among psychologists and a growing fragmentation in
      the field. To be sure, research into the psychology of creativity has grown
      theoretically and methodologically sophisticated, and researchers have made
      important contributions from an ever-expanding variety of disciplines. But this
      expansion has not come without a price. Investigators in one subfield often seem
      unaware of advances in another. Deeper understanding requires more
      interdisciplinary research, based on a systems view of creativity that recognizes
      a variety of interrelated forces operating at multiple levels.

PMID- 19575606
TI  - Peer contagion in child and adolescent social and emotional development.
AB  - In this article, we examine the construct of peer contagion in childhood and
      adolescence and review studies of child and adolescent development that have
      identified peer contagion influences. Evidence suggests that children's
      interactions with peers are tied to increases in aggression in early and middle
      childhood and amplification of problem behaviors such as drug use, delinquency,
      and violence in early to late adolescence. Deviancy training is one mechanism
      that accounts for peer contagion effects on problem behaviors from age 5 through
      adolescence. In addition, we discuss peer contagion relevant to depression in
      adolescence, and corumination as an interactive process that may account for
      these effects. Social network analyses suggest that peer contagion underlies the
      influence of friendship on obesity, unhealthy body images, and expectations.
      Literature is reviewed that suggests how peer contagion effects can undermine the
      goals of public education from elementary school through college and impair the
      goals of juvenile corrections systems. In particular, programs that "select"
      adolescents at risk for aggregated preventive interventions are particularly
      vulnerable to peer contagion effects. It appears that a history of peer rejection
      is a vulnerability factor for influence by peers, and adult monitoring,
      supervision, positive parenting, structure, and self-regulation serve as
      protective factors.

PMID- 19575611
TI  - Negotiation.
AB  - Negotiation occurs whenever people cannot achieve their own goals without the
      cooperation of others. Our review highlights recent empirical research that
      investigates this ubiquitous social activity. We selectively review descriptive
      research emerging from social psychology and organizational behavior. This
      research examines negotiation behavior and outcomes at five levels of analysis:
      intrapersonal, interpersonal, group, organizational, and virtual. At each level,
      we review research on negotiation processes and outcomes, and we discuss the
      implications of various processes and outcomes for the two functions of
      negotiation: value creation (integrative negotiation) and value claiming
      (distributive negotiation).

PMID- 19575612
TI  - Somesthetic senses.
AB  - This is a review of recent advances in our understanding of the sensory
      modalities of touch, temperature sensitivity, and pain. Most of the research
      described is psychophysical or perceptual in nature, but physiological and
      imaging studies are included when they sharpen issues or reveal underlying
      mechanisms. Coverage of touch research comprises the subjects of acuity,
      vibrotaction and texture perception, perception of location and movement, tactile
      attention, and cross-modal phenomena. For pain, the covered topics are central
      sensitization, pain-touch and pain-pain interactions, placebo effects, the role
      of attention and emotion in pain, and the genetics of pain. For touch, the topics
      are arranged roughly in order of increasing cognitive involvement, but such an
      ordering is not feasible for pain, where attitudes and expectations can
      substantially affect even the most "sensory" of judgments.

PMID- 19575613
TI  - Neuroethics: the ethical, legal, and societal impact of neuroscience.
AB  - Advances in cognitive, affective, and social neuroscience raise a host of new
      questions concerning the ways in which neuroscience can and should be used. These
      advances also challenge our intuitions about the nature of humans as moral and
      spiritual beings. Neuroethics is the new field that grapples with these issues.
      The present article surveys a number of applications of neuroscience to such
      diverse arenas as marketing, criminal justice, the military, and worker
      productivity. The ethical, legal, and societal effects of these applications are
      discussed. Less practical, but perhaps ultimately more consequential, is the
      impact of neuroscience on our worldview and our understanding of the human
      person.

PMID- 19575614
TI  - Stress hormone regulation: biological role and translation into therapy.
AB  - Stress is defined as a state of perturbed homeostasis following endangerment that
      evokes manifold adaptive reactions, which are summarized as the stress response.
      In the case of mental stress, the adaptive response follows the perception of
      endangerment. Different peptides, steroids, and biogenic amines operate the
      stress response within the brain and also after they have been released into
      circulation. We focus in this review on the biological roles of corticosteroids,
      corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP), and we
      evaluate the effects of treatments directed against the actions of these
      hormones. CRH and AVP are the central drivers of the stress hormone system, but
      they also act as neuromodulators in the brain, affecting higher mental functions
      including emotion, cognition, and behavior. When released toward the pituitary,
      these central neuropeptides elicit corticotrophin into the periphery, which
      activates corticosteroid release from the adrenal cortex. These stress hormones
      are essential for the adequate adaptation to stress, but they can also evoke
      severe clinical conditions once persistently hypersecreted. Depression and
      anxiety disorders are prominent examples of stress-related disorders associated
      with an impaired regulation of stress hormones. We summarize the effects of drugs
      acting at specific targets of the stress hormone axis, and we discuss their
      potential use as next-generation antidepressant medications. Such treatments
      require the identification of patients that will optimally benefit from such
      specific interventions. These could be a first step into personalized medicine
      using treatments tailored to the specific pathology of the patients.

PMID- 19575616
TI  - The psychology of academic achievement.
AB  - Educational psychology has generated a prolific array of findings about factors
      that influence and correlate with academic achievement. We review select findings
      from this voluminous literature and identify two domains of psychology:
      heuristics that describe generic relations between instructional designs and
      learning, which we call the psychology of "the way things are," and findings
      about metacognition and self-regulated learning that demonstrate learners
      selectively apply and change their use of those heuristics, which we call the
      psychology of "the way learners make things." Distinguishing these domains
      highlights a need to marry two approaches to research methodology: the classical
      approach, which we describe as snapshot, bookend, between-group experimentation;
      and a microgenetic approach that traces proximal cause-effect bonds over time to
      validate theoretical accounts of how learning generates achievements. We argue
      for fusing these methods to advance a validated psychology of academic
      achievement.

PMID- 19575615
TI  - Patterns of gender development.
AB  - A comprehensive theory of gender development must describe and explain long-term
      developmental patterning and changes and how gender is experienced in the short
      term. This review considers multiple views on gender patterning, illustrated with
      contemporary research. First, because developmental research involves
      understanding normative patterns of change with age, several theoretically
      important topics illustrate gender development: how children come to recognize
      gender distinctions and understand stereotypes, and the emergence of prejudice
      and sexism. Second, developmental researchers study the stability of individual
      differences over time, which elucidates developmental processes. We review
      stability in two domains-sex segregation and activities/interests. Finally, a new
      approach advances understanding of developmental patterns, based on dynamic
      systems theory. Dynamic systems theory is a metatheoretical framework for
      studying stability and change, which developed from the study of complex and
      nonlinear systems in physics and mathematics. Some major features and examples
      show how dynamic approaches have been and could be applied in studying gender
      development.

PMID- 19575617
TI  - Learning: from association to cognition.
AB  - Since the very earliest experimental investigations of learning, tension has
      existed between association-based and cognitive theories. Associationism accounts
      for the phenomena of both conditioning and "higher" forms of learning via
      concepts such as excitation, inhibition, and reinforcement, whereas cognitive
      theories assume that learning depends on hypothesis testing, cognitive models,
      and propositional reasoning. Cognitive theories have received considerable
      impetus in regard to both human and animal learning from recent research
      suggesting that the key illustration of cue selection in learning, blocking,
      often arises from inferential reasoning. At the same time, a dichotomous view
      that separates noncognitive, unconscious (implicit) learning from cognitive,
      conscious (explicit) learning has gained favor. This review selectively describes
      key findings from this research, evaluates evidence for and against associative
      and cognitive explanatory constructs, and critically examines both the
      dichotomous view of learning as well as the claim that learning can occur
      unconsciously.

PMID- 19575619
TI  - A taxonomy of external and internal attention.
AB  - Attention is a core property of all perceptual and cognitive operations. Given
      limited capacity to process competing options, attentional mechanisms select,
      modulate, and sustain focus on information most relevant for behavior. A
      significant problem, however, is that attention is so ubiquitous that it is
      unwieldy to study. We propose a taxonomy based on the types of information that
      attention operates over--the targets of attention. At the broadest level, the
      taxonomy distinguishes between external attention and internal attention.
      External attention refers to the selection and modulation of sensory information.
      External attention selects locations in space, points in time, or modality
      specific input. Such perceptual attention can also select features defined across
      any of these dimensions, or object representations that integrate over space,
      time, and modality. Internal attention refers to the selection, modulation, and
      maintenance of internally generated information, such as task rules, responses,
      long-term memory, or working memory. Working memory, in particular, lies closest
      to the intersection between external and internal attention. The taxonomy
      provides an organizing framework that recasts classic debates, raises new issues,
      and frames understanding of neural mechanisms.

PMID- 19575620
TI  - Hippocampal-neocortical interactions in memory formation, consolidation, and
      reconsolidation.
AB  - This review, focusing on work using animals, updates a theoretical approach whose
      aim is to translate neuropsychological ideas about the psychological and
      anatomical organization of memory into the neurobiological domain. It is
      suggested that episodic-like memory consists of both automatic and controlled
      components, with the medial temporal mediation of memory encoding including
      neurobiological mechanisms that are primarily automatic or incidental. These
      ideas, in the cognitive and behavioral domain, are linked to neurophysiological
      ideas about cellular consolidation concerning synaptic potentiation, particularly
      the relationship between protein synthesis-dependent long-term changes and
      shorter-lasting post-translational mechanisms. Ideas from psychology about mental
      schemas are considered in relation to the phenomenon of systems consolidation
      and, specifically, about how prior knowledge can alter the rate at which
      consolidation occurs. Finally, the hippocampal-neocortical interactions theory is
      updated in relation to reconsolidation, a process that enables updating of stored
      memory traces in response to novelty.

PMID- 19575618
TI  - Social and emotional aging.
AB  - The past several decades have witnessed unidimensional decline models of aging
      give way to life-span developmental models that consider how specific processes
      and strategies facilitate adaptive aging. In part, this shift was provoked by the
      stark contrast between findings that clearly demonstrate decreased biological,
      physiological, and cognitive capacity and those suggesting that people are
      generally satisfied in old age and experience relatively high levels of emotional
      well-being. In recent years, this supposed "paradox" of aging has been reconciled
      through careful theoretical analysis and empirical investigation. Viewing aging
      as adaptation sheds light on resilience, well-being, and emotional distress
      across adulthood.

PMID- 19575622
TI  - Child maltreatment and memory.
AB  - Exposure to childhood trauma, especially child maltreatment, has important
      implications for memory of emotionally distressing experiences. These
      implications stem from cognitive, socio-emotional, mental health, and
      neurobiological consequences of maltreatment and can be at least partially
      explained by current theories concerning the effects of childhood trauma. In this
      review, two main hypotheses are advanced: (a) Maltreatment in childhood is
      associated with especially robust memory for emotionally distressing material in
      many individuals, but (b) maltreatment can impair memory for such material in
      individuals who defensively avoid it. Support for these hypotheses comes from
      research on child abuse victims' memory and suggestibility regarding distressing
      but nonabusive events, memory for child abuse itself, and autobiographical
      memory. However, more direct investigations are needed to test precisely when and
      how childhood trauma affects memory for emotionally significant, distressing
      experiences. Legal implications and future directions are discussed.

PMID- 19575623
TI  - Speech perception and language acquisition in the first year of life.
AB  - During the first year of life, infants pass important milestones in language
      development. We review some of the experimental evidence concerning these
      milestones in the domains of speech perception, phonological development, word
      learning, morphosyntactic acquisition, and bilingualism, emphasizing their
      interactions. We discuss them in the context of their biological underpinnings,
      introducing the most recent advances not only in language development, but also
      in neighboring areas such as genetics and the comparative research on animal
      communication systems. We argue for a theory of language acquisition that
      integrates behavioral, cognitive, neural, and evolutionary considerations and
      proposes to unify previously opposing theoretical stances, such as statistical
      learning, rule-based nativist accounts, and perceptual learning theories.

PMID- 19575624
TI  - The disaggregation of within-person and between-person effects in longitudinal
      models of change.
AB  - Longitudinal models are becoming increasingly prevalent in the behavioral
      sciences, with key advantages including increased power, more comprehensive
      measurement, and establishment of temporal precedence. One particularly salient
      strength offered by longitudinal data is the ability to disaggregate between
      person and within-person effects in the regression of an outcome on a time
      varying covariate. However, the ability to disaggregate these effects has not
      been fully capitalized upon in many social science research applications. Two
      likely reasons for this omission are the general lack of discussion of
      disaggregating effects in the substantive literature and the need to overcome
      several remaining analytic challenges that limit existing quantitative methods
      used to isolate these effects in practice. This review explores both substantive
      and quantitative issues related to the disaggregation of effects over time, with
      a particular emphasis placed on the multilevel model. Existing analytic methods
      are reviewed, a general approach to the problem is proposed, and both the
      existing and proposed methods are demonstrated using several artificial data
      sets. Potential limitations and directions for future research are discussed, and
      recommendations for the disaggregation of effects in practice are offered.

PMID- 19575621
TI  - Structural plasticity and hippocampal function.
AB  - The hippocampus is a region of the mammalian brain that shows an impressive
      capacity for structural reorganization. Preexisting neural circuits undergo
      modifications in dendritic complexity and synapse number, and entirely novel
      neural connections are formed through the process of neurogenesis. These types of
      structural change were once thought to be restricted to development. However, it
      is now generally accepted that the hippocampus remains structurally plastic
      throughout life. This article reviews structural plasticity in the hippocampus
      over the lifespan, including how it is investigated experimentally. The
      modulation of structural plasticity by various experiential factors as well as
      the possible role it may have in hippocampal functions such as learning and
      memory, anxiety, and stress regulation are also considered. Although significant
      progress has been made in many of these areas, we highlight some of the
      outstanding issues that remain.

PMID- 19575626
TI  - Love in the fourth dimension.
AB  - Psychologists' efforts to understand love began in the mid-twentieth century. The
      fact that they continue apace in the twenty-first century reflects increased
      awareness of the importance of love to understanding relationship phenomena and
      acknowledgment that an understanding of love has yet to be achieved. This article
      (a) describes one source of increased recognition that the present confusions
      surrounding love must be transcended if progress is to be made in understanding
      many relationship phenomena; (b) discusses the failure to explicate the love
      construct, which constitutes the major obstacle to the study of love phenomena;
      (c) discusses the need for a temporal model of love in relationships; and (d)
      suggests that it is important to consider the presence or absence of four types
      of love, each of which appears to be associated with different causal conditions
      and thus is likely to have a different temporal course as an adult relationship
      moves through time.

PMID- 19575628
TI  - Cost-effectiveness analysis of micafungin versus caspofungin for treatment of
      systemic Candida infections in the UK.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of micafungin compared to
      caspofungin in the treatment of systemic Candida infections (SCIs) in the UK,
      including invasive candidiasis and candidaemia. RESEARCH DESIGN AND METHODS: Cost
      effectiveness of both echinocandin antifungal drugs was estimated using decision
      analysis. Response to treatment, resource utilisation, and costs in the model
      were derived from a phase 3, head-to-head comparative trial. The model includes
      only data directly related to the treatment of the systemic Candida infection
      over the study duration (a maximum period of 14 weeks). Transition probabilities
      were calculated based on the efficacy results from the clinical trial. MAIN
      OUTCOME MEASURES: The model's effectiveness outcome is surviving patients who are
      successfully treated, based on the absence of signs and symptoms, radiographic
      abnormalities, and culture/histologic evidence associated with the fungal
      infection. In addition, subgroup analyses were performed to identify cost
      effectiveness in several specific patient groups. RESULTS: The total medical
      treatment costs for the micafungin group were pound 29,095, which is similar to
      the total costs for the caspofungin group (pound 29,953). In the micafungin arm
      60% of the patients and in the caspofungin arm 58% of the patients were
      successfully treated and alive. Cost-effectiveness ratio of micafungin was pound
      48,771, and of caspofungin pound 52,066 per successfully treated patient. Because
      the costs are lower and the effectiveness is higher for micafungin in comparison
      with caspofungin, micafungin is more cost-effective than caspofungin. However,
      probabilistic sensitivity and subgroup analysis show that the differences cannot
      be considered significant due to a large variance although micafungin remained
      the most cost-effective option throughout all but one of the sensitivity
      analyses. CONCLUSIONS: Costs and effects of micafungin compare to those of
      caspofungin in the treatment of systemic Candida infections in the UK. The
      results indicate that micafungin is cost-effective compared to caspofungin,
      although the difference was not found to be significant.

PMID- 19575629
TI  - Recent developments in clopidogrel pharmacology and their relation to clinical
      outcomes.
AB  - Oral antiplatelet therapy with clopidogrel and aspirin is an important and widely
      prescribed strategy to prevent ischemic events in patients with cardiovascular
      diseases. However, the occurrence of thrombotic events including stent thrombosis
      is still high (> 10%). Current practice guidelines are mainly based on large
      scale trials focusing on clinical endpoints and 'one size fits all' strategies of
      treating all patients with the same clopidogrel doses. Pharmacodynamic studies
      have demonstrated that the latter strategy is associated with wide response
      variability where a substantial percentage of patients show nonresponsivenes.
      Translational research studies have established the relation between clopidogrel
      nonresponsivenes or high on-treatment platelet reactivity to adverse clinical
      events, thereby establishing clopidogrel nonresponsivenes as an important
      emerging clinical entity. Clopidogrel response variability is primarily a
      pharmacokinetic phenomenon associated with insufficient active metabolite
      generation that is secondary to i) limited intestinal absorption affected by an
      ABCB1 gene polymorphism; ii) functional variability in P450 isoenzyme activity;
      and iii) a genetic polymorphism of CYP450 isoenzymes. Personalized antiplatelet
      treatment with higher clopidogrel doses in selected patients or with newer more
      potent P2Y(12) receptor blockers based on individual platelet function
      measurement can overcome some of the limitations of current clopidogrel
      treatment.

PMID- 19575625
TI  - Cognitive neural prosthetics.
AB  - The cognitive neural prosthetic (CNP) is a very versatile method for assisting
      paralyzed patients and patients with amputations. The CNP records the cognitive
      state of the subject, rather than signals strictly related to motor execution or
      sensation. We review a number of high-level cortical signals and their
      application for CNPs, including intention, motor imagery, decision making,
      forward estimation, executive function, attention, learning, and multi-effector
      movement planning. CNPs are defined by the cognitive function they extract, not
      the cortical region from which the signals are recorded. However, some cortical
      areas may be better than others for particular applications. Signals can also be
      extracted in parallel from multiple cortical areas using multiple implants, which
      in many circumstances can increase the range of applications of CNPs. The CNP
      approach relies on scientific understanding of the neural processes involved in
      cognition, and many of the decoding algorithms it uses also have parallels to
      underlying neural circuit functions.

PMID- 19575632
TI  - Thoracoscopic lobectomy for severe bronchiectasis in children.
AB  - BACKGROUND/PURPOSE: Lung resection should be considered for severe, localized
      bronchiectasis causing recurrent infections in patients with cystic fibrosis (CF)
      and other diseases. This series represents our experience and results with
      thoracoscopic lobectomy for the treatment of severe bronchiectasis confined to a
      single lobe. METHODS: Nineteen thoracoscopic anatomic lobectomies were performed
      between July 1994 and August 2008. Patient age at the time of surgery ranged from
      14 months to 22 years. Left lower lobectomy was the most frequently performed
      procedure (n = 9). Eight patients suffered from CF, 5 had chronic pneumonia, 2
      had chronic aspiration, and 3 had other diagnoses. RESULTS: Mean operative time
      was 162 minutes (range, 65-300), and no cases required a conversion to
      thoracotomy. The mean duration of postoperative chest tube drainage was 3.2 days
      (range, 1-9). The mean postoperative length of stay was 3.6 days (range, 1-12).
      One patient had a prolonged air leak lasting 9 days, which resolved with the
      placement of a second chest tube. Another had a small hydropneumothorax, which
      persisted after chest tube removal but resolved spontaneously. CONCLUSIONS:
      Thoracoscopic lobectomy for severe lobar bronchiectasis with recurrent infection
      is technically challenging, but appears to be safe and effective. Avoidance of a
      thoracotomy, in this group of patients, allows for earlier mobilization, less
      postoperative pain with cough and chest physiotherapy, and faster recovery. There
      appear to be significant benefits in these patients with chronic respiratory
      illnesses.

PMID- 19575633
TI  - Early experience with single-port laparoscopic surgery in children.
AB  - INTRODUCTION: The current paradigm in laparoscopic surgery is for each instrument
      to enter the abdomen through its own separate incision. The advent of newer
      laparoscopic trocars and instruments now allows for all instruments to enter
      through a single incision. This may lead to less pain and improved cosmetic
      outcome. Single-incision laparoscopic surgery (SILS) has recently been described
      in adults. In this article, we report our preliminary experience of SILS in
      children. METHODS: A retrospective review was performed of the operative database
      at Rainbow Babies and Children's Hospital (Cleveland, OH) from March 2008 to
      March 2009, looking for all cases that were performed through a single
      laparoscopic incision. RESULTS: A total of 72 SILS cases were performed. These
      included cholecystectomy, splenectomy, intussusception reduction, gastrostomy
      tube placement, thoracoscopic lung biopsy, thoracoscopic decortication, and
      appendectomy. Five appendectomies were converted to traditional three-port
      laparoscopy. There were two umbilical wound infections after an appendectomy.
      There were no other complications. CONCLUSION: Preliminary experience with SILS
      in children appears to be safe and effective. Greater numbers and a prospective
      trial will be necessary to assess the true benefit of this approach.

PMID- 19575634
TI  - Microbiological contamination during transgastric and transvaginal endoscopic
      techniques.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) has gained widespread
      interest as a potentially alternative to laparoscopic surgery, but concerns over
      peritoneal contaminations are unsolved. The aim of our study was to assess the
      safety of transluminal surgery by investigating the intraperitoneal bacterial
      load and contamination during transgastric and transvaginal surgeries. Twelve
      female pigs underwent transgastric (n = 7; tubal ligation and oophorectomy) and
      transvaginal procedures (n = 5; cholecystectomy). All animals were sacrificed
      after 2 weeks. The procedures were performed by using a double-channel endoscope
      (GIF-2T160; Olympus, Tokyo, Japan) under general anesthesia. Peritoneal fluid
      sampling was taken immediately after entry into the abdomen, at the end of the
      surgical procedure and during the autopsy, and sent for microbiologic assessment.
      In the transgastric group, 6 animals completed the surgical procedures and
      survived. Three pigs experienced signs of postoperative peritonitis with
      abscesses and adhesions visible and Escherichia Coli isolated at autopsy. In the
      transvaginal group, a cholecystectomy was performed without technical problems in
      all animals. No signs of postoperative sepsis nor growth in the microbiologic
      samples were recorded. In conclusion, the transvaginal approach seemed to be
      safer and produced less intra-abdominal contamination and sepsis, compared to the
      transgastric approach. Although both transgastric tubal ligation and oophorectomy
      and transvaginal cholecystectomy were feasible using equipment and accessories
      currently available for conventional endoscopy, new procedure-specific
      instruments and equipment should be developed to allow the operator safer access
      into the peritoneum.

PMID- 19575635
TI  - Risk of ventriculoperitoneal shunt infections after laparoscopic placement of
      Chait Trapdoor cecostomy catheters in children.
AB  - INTRODUCTION: Laparoscopic placement of Chait Trapdoor (Cook, Bloomington, IN)
      cecosotomy catheters has been practiced in our institution since 1999. Chait
      cecostomy catheters allow antegrade irrigation of the colon without the
      complications associated with appendicostomies. Although the use of laparoscopy
      allows precise placement of these catheters into the cecum under direct vision,
      the presence of a concomitant ventriculoperitoneal (VP) shunt raises concerns for
      the potential for a shunt infection. MATERIALS AND METHODS: This is a
      retrospective review of all patients with VP shunts who underwent laparoscopic
      placement of a Chait cecostomy catheter from 1999 to 2008. We recorded patient
      demographics, indication for VP shunt placement, the date of the most recent
      shunt operation, the method of cecal fixation, follow-up duration, and episodes
      of shunt infection. RESULTS: Sixteen patients with spina bifida and VP shunts who
      underwent laparoscopic placement of a Chait cecostomy catheter were identified.
      There were 12 males. Mean follow-up was 46 +/- 27 months (range, 3-87). Two
      patients (12.5%) developed a VP shunt infection related to the placement of their
      cecostomy catheter. One shunt infection occurred 5 days postoperatively and the
      other occurred several years later, when the shunt and cecostomy catheter tracts
      merged in the subcutaneous tissue. Both patients underwent shunt externalization.
      CONCLUSIONS: Cecostomy catheter placement in patients with preexisting VP shunts
      may increase the risk of shunt infections. Our series illustrates two different
      mechanisms by which a VP shunt can become infected after this procedure. In the
      first case, leakage of enteric content from a poorly sealed tract probably
      resulted in the shunt infection. More secure fixation of the cecum to the
      abdominal wall, using intracorporeal sutures rather than T-fasteners, may avoid
      this complication. The second complication could have been avoided if the
      cecostomy catheter had been placed further away from the VP shunt.

PMID- 19575636
TI  - A novel technique for the surgical treatment of achalasia in children: evaluated
      with postoperative esophageal manometry.
AB  - INTRODUCTION: The current surgical treatment for achalasia in the pediatric
      population is the laparoscopic Heller myotomy with or without a fundoplication.
      Although medical management with serial dilations and botulism toxin injections
      may offer short-term benefits, surgical therapy offers definitive treatment. In
      this article, we propose a modified surgical technique that avoids pitfalls
      associated with the standard procedure and evaluated our results with
      postoperative manometry. METHODS: Charts were reviewed for all patients having
      undergone the proposed surgical procedure. Seven patients underwent postoperative
      manometry, while 12 answered a short questionnaire. RESULTS: While manometry
      showed a statistically significant reduction of lower esophageal sphincter tone,
      from a mean preoperative lower esophageal sphincter (LES) of 56.1 mm Hg (SD =
      8.88, 95% CI = 50.36-61.93) to mean postoperative LES tone of 11.69 mm Hg (SD =
      11.69, 95% CI = 3.287-20.08; P < 0.0001), peristalsis was not consistently
      affected, although a trend toward improvement was noted. Symptoms related to
      dysphagia were noted in 42% of patients postoperatively but were mild, while all
      patients showed improved feeding tolerance and weight gain. Interestingly,
      patients with a postoperative LES pressure <12 mm Hg were more likely to have no
      symptoms, although this LES pressure was arbitrarily chosen and the study was not
      powered to detect this outcome (chi-square = 3.73, df = 1; P < 0.053).
      CONCLUSIONS: The proposed surgical technique for the treatment of achalasia in
      children was successful at improving feeding and weight gain and attaining normal
      postoperative LES tone; however, underlying esophageal dysmotility persisted.

PMID- 19575637
TI  - Coordination of lipid metabolism in membrane biogenesis.
AB  - Bilayer synthesis during membrane biogenesis involves the concerted assembly of
      multiple lipid species, requiring coordination of the level of lipid synthesis,
      uptake, turnover, and subcellular distribution. In this review, we discuss some
      of the salient conclusions regarding the coordination of lipid synthesis that
      have emerged from work in mammalian and yeast cells. The principal instruments of
      global control are a small number of transcription factors that target a wide
      range of genes encoding enzymes that operate in a given metabolic pathway.
      Critical in mammalian cells are sterol regulatory element binding proteins
      (SREBPs) that stimulate expression of genes for the uptake and synthesis of
      cholesterol and fatty acids. From work with Saccharomyces cerevisiae, much has
      been learned about glycerophospholipid and ergosterol regulation through
      Ino2p/Ino4p and Upc2p transcription factors, respectively. Lipid supply is fine
      tuned through a multitude of negative feedback circuits initiated by both end
      products and intermediates of lipid synthesis pathways. Moreover, there is
      evidence that the diversity of membrane lipids is maintained through cross
      regulatory effects, whereby classes of lipids activate the activity of enzymes
      operating in another metabolic branch.

PMID- 19575638
TI  - Innovations in teaching undergraduate biology and why we need them.
AB  - A growing revolution is under way in the teaching of introductory science to
      undergraduates. It is driven by concerns about American competitiveness as well
      as results from recent educational research, which explains why traditional
      teaching approaches in large classes fail to reach many students and provides a
      basis for designing improved methods of instruction. Discipline-based educational
      research in the life sciences and other areas has identified several innovative
      promising practices and demonstrated their effectiveness for increasing student
      learning. Their widespread adoption could have a major impact on the introductory
      training of biology students.

PMID- 19575641
TI  - Conflicting views on the membrane fusion machinery and the fusion pore.
AB  - Fast exocytosis of synaptic vesicles differs from other membrane fusion reactions
      by being under tight temporal control by the intracellular calcium concentration.
      This is achieved by subjecting the SNARE-dependent fusion pathway to additional
      layers of control, both upstream and downstream of the assembly of the fusogenic
      SNARE-complex. Here, I review conflicting views on the function of the core
      fusion machinery consisting of the SNAREs, Munc18, complexin, and synaptotagmin.
      Munc18 controls docking of vesicles to the plasma membrane and initial SNARE
      complex assembly, whereas complexin and synaptotagmin cooperate in holding the
      SNARE complex in an intermediate release-ready or cocked state. Different effects
      of complexin and synaptotagmin shape the energy landscape for fusion and make
      final fusion calcium triggered. The final steps are fusion pore formation and
      expansion, which allow release of the water-soluble vesicle content. The fusion
      pore remains the most elusive part of the exocytosis pathway, owing to its short
      lifetime.

PMID- 19575639
TI  - Membrane traffic within the Golgi apparatus.
AB  - Newly synthesized secretory cargo molecules pass through the Golgi apparatus
      while resident Golgi proteins remain in the organelle. However, the pathways of
      membrane traffic within the Golgi are still uncertain. Most of the available data
      can be accommodated by the cisternal maturation model, which postulates that
      Golgi cisternae form de novo, carry secretory cargoes forward and ultimately
      disappear. The entry face of the Golgi receives material that has been exported
      from transitional endoplasmic reticulum sites, and the exit face of the Golgi is
      intimately connected with endocytic compartments. These conserved features are
      enhanced by cell-type-specific elaborations such as tubular connections between
      mammalian Golgi cisternae. Key mechanistic questions remain about the formation
      and maturation of Golgi cisternae, the recycling of resident Golgi proteins, the
      origins of Golgi compartmental identity, the establishment of Golgi architecture,
      and the roles of Golgi structural elements in membrane traffic.

PMID- 19575640
TI  - Asymmetric cell divisions and asymmetric cell fates.
AB  - The regulation of self-renewal, cell diversity, and differentiation can occur by
      modulating symmetric and asymmetric cell divisions. Remarkably, asymmetric cell
      divisions can arise through multiple processes in which molecules in the
      cytoplasm and nucleus, as well as template "immortal" DNA strands, can segregate
      to one daughter cell during cell division. Explaining how these events direct
      distinct daughter cell fates is a major challenge to understanding how the
      organism is assembled and maintained for a lifetime. Numerous technical issues
      that are associated with assessing how distinct cell fates are executed in vivo
      have resulted in divergent interpretations of experimental findings. This review
      addresses some of these points and considers different developmental model
      systems that attempt to investigate how cell fate decisions are determined, as
      well as the molecules that guide these choices.

PMID- 19575643
TI  - The biogenesis and function of PIWI proteins and piRNAs: progress and prospect.
AB  - The evolutionarily conserved Argonaute/PIWI (AGO/PIWI, also known as PAZ-PIWI
      domain or PPD) family of proteins is crucial for the biogenesis and function of
      small noncoding RNAs (ncRNAs). This family can be divided into AGO and PIWI
      subfamilies. The AGO proteins are ubiquitously present in diverse tissues. They
      bind to small interfering RNAs (siRNAs) and microRNAs (miRNAs). In contrast, the
      PIWI proteins are predominantly present in the germline and associate with a
      novel class of small RNAs known as PIWI-interacting RNAs (piRNAs). Tens of
      thousands of piRNA species, typically 24-32 nucleotide (nt) long, have been found
      in mammals, zebrafish, and Drosophila. Most piRNAs appear to be generated from a
      small number of long single-stranded RNA precursors that are often encoded by
      repetitive intergenic sequences in the genome. PIWI proteins play crucial roles
      during germline development and gametogenesis of many metazoan species, from
      germline determination and germline stem cell (GSC) maintenance to meiosis,
      spermiogenesis, and transposon silencing. These diverse functions may involve
      piRNAs and may be achieved via novel mechanisms of epigenetic and
      posttranscriptional regulation.

PMID- 19575644
TI  - Navigating ECM barriers at the invasive front: the cancer cell-stroma interface.
AB  - A seminal event in cancer progression is the ability of the neoplastic cell to
      mobilize the necessary machinery to breach surrounding extracellular matrix
      barriers while orchestrating a host stromal response that ultimately supports
      tissue-invasive and metastatic processes. With over 500 proteolytic enzymes
      identified in the human genome, interconnecting webs of protease-dependent and
      protease-independent processes have been postulated to drive the cancer cell
      invasion program via schemes of daunting complexity. Increasingly, however, a
      body of evidence has begun to emerge that supports a unifying model wherein a
      small group of membrane-tethered enzymes, termed the membrane-type matrix
      metalloproteinases (MT-MMPs), plays a dominant role in regulating cancer cell, as
      well as stromal cell, traffic through the extracellular matrix barriers assembled
      by host tissues in vivo. Understanding the mechanisms that underlie the
      regulation and function of these metalloenzymes as host cell populations traverse
      the dynamic extracellular matrix assembled during neoplastic states should
      provide new and testable theories regarding cancer invasion and metastasis.

PMID- 19575642
TI  - The molecular basis of organ formation: insights from the C. elegans foregut.
AB  - The digestive tracts of many animals are epithelial tubes with specialized
      compartments to break down food, remove wastes, combat infection, and signal
      nutrient availability. C. elegans possesses a linear, epithelial gut tube with
      foregut, midgut, and hindgut sections. The simple anatomy belies the
      developmental complexity that is involved in forming the gut from a pool of
      heterogeneous precursor cells. Here, I focus on the processes that specify cell
      fates and control morphogenesis within the embryonic foregut (pharynx) and the
      developmental roles of the pharynx after birth. Maternally donated factors in the
      pregastrula embryo converge on pha-4, a FoxA transcription factor that specifies
      organ identity for pharyngeal precursors. Positive feedback loops between PHA-4
      and other transcription factors ensure commitment to pharyngeal fate. Binding
      site affinity of PHA-4 for its target promoters contributes to the progression of
      the pharyngeal precursors towards differentiation. During morphogenesis, the
      pharyngeal precursors form an epithelial tube in a process that is independent of
      cadherins, catenins, and integrins but requires the kinesin zen-4/MKLP1. After
      birth, the pharynx and/or pha-4 are involved in repelling pathogens and
      controlling aging.

PMID- 19575645
TI  - Mechanisms of growth and homeostasis in the Drosophila wing.
AB  - Animal shape and size is controlled with amazing precision during development.
      External factors such as nutrient availability and crowding can alter overall
      animal size, but individual body parts scale reproducibly to match the body even
      with challenges from a changing environment. How is such precision achieved?
      Here, we review selected research from the last few years in Drosophila--arguably
      the premier genetic model for the study of animal growth--that sheds light on how
      body and tissue size are regulated by forces intrinsic to individual organs. We
      focus on two topics currently under intense study: the influence of pattern
      regulators on organ and tissue growth and the role of local competitive
      interactions between cells in tissue homeostasis and final size.

PMID- 19575646
TI  - Mechanisms of stem cell self-renewal.
AB  - Self-renewal is the process by which stem cells divide to make more stem cells,
      perpetuating the stem cell pool throughout life. Self-renewal is division with
      maintenance of the undifferentiated state. This requires cell cycle control and
      often maintenance of multipotency or pluripotency, depending on the stem cell.
      Self-renewal programs involve networks that balance proto-oncogenes (promoting
      self-renewal), gate-keeping tumor suppressors (limiting self-renewal), and care
      taking tumor suppressors (maintaining genomic integrity). These cell-intrinsic
      mechanisms are regulated by cell-extrinsic signals from the niche, the
      microenvironment that maintains stem cells and regulates their function in
      tissues. In response to changing tissue demands, stem cells undergo changes in
      cell cycle status and developmental potential over time, requiring different self
      renewal programs at different stages of life. Reduced stem cell function and
      tissue regenerative capacity during aging are caused by changes in self-renewal
      programs that augment tumor suppression. Cancer arises from mutations that
      inappropriately activate self-renewal programs.

PMID- 19575648
TI  - Genetic control of bone formation.
AB  - In the past few years, our molecular understanding of bone formation has
      continued to increase. This review aims to present a comprehensive view of the
      current state of knowledge in the field. Thus, it will cover our current
      knowledge of chondrogenesis and osteoblastogenesis. It will also cover the most
      salient aspects of osteoblast function.

PMID- 19575650
TI  - Tethering factors as organizers of intracellular vesicular traffic.
AB  - Intracellular trafficking entails the budding, transport, tethering, and fusion
      of transport vesicles and other membrane carriers. Here we review recent progress
      toward a mechanistic understanding of vesicle tethering. The known tethering
      factors are large complexes important for one or more intracellular trafficking
      pathways and are capable of interacting directly with many of the other principal
      components of the cellular trafficking machinery. Our review emphasizes recent
      developments in the in vitro reconstitution of vesicle tethering and the
      structural characterization of multisubunit tethering factors. The combination of
      these and other approaches has led to exciting progress toward understanding how
      these essential nanomachines work.

PMID- 19575647
TI  - Mechanical integration of actin and adhesion dynamics in cell migration.
AB  - Directed cell migration is a physical process that requires dramatic changes in
      cell shape and adhesion to the extracellular matrix. For efficient movement,
      these processes must be spatiotemporally coordinated. To a large degree, the
      morphological changes and physical forces that occur during migration are
      generated by a dynamic filamentous actin (F-actin) cytoskeleton. Adhesion is
      regulated by dynamic assemblies of structural and signaling proteins that couple
      the F-actin cytoskeleton to the extracellular matrix. Here, we review current
      knowledge of the dynamic organization of the F-actin cytoskeleton in cell
      migration and the regulation of focal adhesion assembly and disassembly with an
      emphasis on how mechanical and biochemical signaling between these two systems
      regulate the coordination of physical processes in cell migration.

PMID- 19575651
TI  - Common factors regulating patterning of the nervous and vascular systems.
AB  - The vascular and the nervous systems of vertebrates share many features with
      similar and often overlapping anatomy. The parallels between these two systems
      extend to the molecular level, where recent work has identified ever-increasing
      similarities between the molecular mechanisms employed in the specification,
      differentiation, and patterning of both systems. This review discusses some of
      the most recent literature on this subject, with particular emphasis on the roles
      that the Ephrin, Semaphorin, Netrin, and Slit signaling pathways play in vascular
      development.

PMID- 19575654
TI  - From mouse egg to mouse embryo: polarities, axes, and tissues.
AB  - This review describes the three classical models (mosaic, positional, and
      polarization) proposed to explain blastocyst formation and summarizes the
      evidence concerning them. It concludes that the polarization model incorporates
      elements of the other two models and best explains most known information. I
      discuss key requirements of a molecular basis for the generation and
      stabilization of polarity and identify ezrin/E-cadherin, PAR proteins, and Cdx2
      as plausible key molecular players. I also discuss the idea of a network process
      operating to build cell allocations progressively into committed differences.
      Finally, this review critically considers the possibility of developmental
      information being encoded within the oocyte and zygote. No final decision can be
      reached on a mechanism of action underlying any encoded information, but a cell
      interaction process model is preferred over one that relies solely on
      differential inheritance.

PMID- 19575656
TI  - Paramutation and development.
AB  - Paramutation describes a heritable change of gene expression that is brought
      about through interactions between homologous chromosomes. Genetic analyses in
      plants and, more recently, in mouse indicate that genomic sequences related to
      transcriptional control and molecules related to small RNA biology are necessary
      for specific examples of paramutation. Some of the molecules identified in maize
      are also required for normal plant development. These observations indicate a
      functional relationship between the nuclear mechanisms responsible for
      paramutation and modes of developmental gene control.

PMID- 19575657
TI  - Collective cell migration.
AB  - For all animals, cell migration is an essential and highly regulated process.
      Cells migrate to shape tissues, to vascularize tissues, in wound healing, and as
      part of the immune response. Unfortunately, tumor cells can also become migratory
      and invade surrounding tissues. Some cells migrate as individuals, but many cell
      types will, under physiological conditions, migrate collectively in tightly or
      loosely associated groups. This includes invasive tumor cells. This review
      discusses different types of collective cell migration, including sheet movement,
      sprouting and branching, streams, and free groups, and highlights recent findings
      that provide insight into cells' organization and behavior. Cells performing
      collective migration share many cell biological characteristics with
      independently migrating cells but, by affecting one another mechanically and via
      signaling, these cell groups are subject to additional regulation and
      constraints. New properties that emerge from this connectivity can contribute to
      shaping, guiding, and ultimately ensuring tissue function.

PMID- 19575655
TI  - Quantitative time-lapse fluorescence microscopy in single cells.
AB  - The cloning of green fluorescent protein (GFP) 15 years ago revolutionized cell
      biology by permitting visualization of a wide range of molecular mechanisms
      within living cells. Though initially used to make largely qualitative
      assessments of protein levels and localizations, fluorescence microscopy has
      since evolved to become highly quantitative and high-throughput. Computational
      image analysis has catalyzed this evolution, enabling rapid and automated
      processing of large datasets. Here, we review studies that combine time-lapse
      fluorescence microscopy and automated image analysis to investigate dynamic
      events at the single-cell level. We highlight examples where single-cell analysis
      provides unique mechanistic insights into cellular processes that cannot be
      otherwise resolved in bulk assays. Additionally, we discuss studies where
      quantitative microscopy facilitates the assembly of detailed 4D lineages in
      developing organisms. Finally, we describe recent advances in imaging technology,
      focusing especially on platforms that allow the simultaneous perturbation and
      quantitative monitoring of biological systems.

PMID- 19575658
TI  - Listeria monocytogenes membrane trafficking and lifestyle: the exception or the
      rule?
AB  - Listeria monocytogenes is an intracellular bacterial pathogen that promotes its
      internalization within nonprofessional phagocytes by interacting with specific
      host cell receptors. L. monocytogenes resides transiently in a membrane-bound
      compartment before escaping into the host cell cytosol where bacterial
      proliferation takes place. Actin-based motility then promotes cell-to-cell
      pathogen spread. Extensive studies on cytoskeleton rearrangements, membrane
      trafficking, and other events have established this microorganism as an archetype
      of cellular function subversion for intracellular parasitism. Here we discuss the
      most significant membrane trafficking pathways hijacked by L. monocytogenes
      during the host cell infection process and compare them to those of other
      intracellular pathogens, in particular Shigella flexneri, Salmonella enterica,
      and Mycobacterium tuberculosis.

PMID- 19575660
TI  - Vernalization: winter and the timing of flowering in plants.
AB  - Plants have evolved many systems to sense their environment and to modify their
      growth and development accordingly. One example is vernalization, the process by
      which flowering is promoted as plants sense exposure to the cold temperatures of
      winter. A requirement for vernalization is an adaptive trait that helps prevent
      flowering before winter and permits flowering in the favorable conditions of
      spring. In Arabidopsis and cereals, vernalization results in the suppression of
      genes that repress flowering. We describe recent progress in understanding the
      molecular basis of this suppression. In Arabidopsis, vernalization involves the
      recruitment of chromatin-modifying complexes to a clade of flowering repressors
      that are silenced epigenetically via histone modifications. We also discuss the
      similarities and differences in vernalization between Arabidopsis and cereals.

PMID- 19575661
TI  - From progenitors to differentiated cells in the vertebrate retina.
AB  - Multipotent retinal progenitors undergo a varied number of divisions to produce
      clones of heterogeneous sizes and cell types. We describe the transition from a
      proliferating progenitor to a differentiated postmitotic cell and discuss how
      controls of proliferation operate within individual cells as well as in the whole
      tissue. We discuss how extracellular and intracellular signaling, transcriptional
      regulation, cell cycle kinetics, interkinetic nuclear migration, orientation of
      cell division, and epigenetic modifications all interact to regulate a
      progenitor's transition from division to differentiation. We also propose some
      directions for future research.

PMID- 19575663
TI  - Signaling in adult neurogenesis.
AB  - The identification of neural stem cells (NSCs) and their contribution to
      continuous neurogenesis has shown that the hippocampus and olfactory bulb are
      plastic. Brain plasticity, achieved at the level of cell genesis, has an
      essential role in the maintenance of brain homeostasis. Via combinatorial
      functions of extrinsic signals and intrinsic programs, adult neurogenesis is
      tightly regulated in a specialized microenvironment, a niche. Misregulated
      neurogenesis is detrimental to normal brain functions and, in extreme cases,
      pathogenic. Hence, understanding signaling in adult neurogenesis is not only
      important to understand the physiological roles of neurogenesis, but also to
      provide knowledge that is essential for developing therapeutic applications using
      NSCs to intervene in the progression of brain diseases.

PMID- 19575662
TI  - The diverse functions of oxysterol-binding proteins.
AB  - Oxysterol-binding protein (OSBP)-related proteins (ORPs) are lipid-binding
      proteins that are conserved from yeast to humans. They are implicated in many
      cellular processes including signaling, vesicular trafficking, lipid metabolism,
      and nonvesicular sterol transport. All ORPs contain an OSBP-related domain (ORD)
      that has a hydrophobic pocket that binds a single sterol. ORDs also contain
      additional membrane-binding surfaces, some of which bind phosphoinositides and
      may regulate sterol binding. Studies in yeast suggest that ORPs function as
      sterol transporters, perhaps in regions where organelle membranes are closely
      apposed. Yeast ORPs also participate in vesicular trafficking, although their
      role is unclear. In mammalian cells, some ORPs function as sterol sensors that
      regulate the assembly of protein complexes in response to changes in cholesterol
      levels. This review will summarize recent advances in our understanding of how
      ORPs bind lipids and membranes and how they function in diverse cellular
      processes.

PMID- 19575666
TI  - WITHDRAWN:
AB  - Ahead of Print article withdrawn by publisher.

PMID- 19575665
TI  - Bacterial Chromosome Segregation.

PMID- 19575667
TI  - Cell motility and mechanics in three-dimensional collagen matrices.
AB  - Fibrous connective tissues provide mechanical support and frameworks for other
      tissues of the body and play an integral role in normal tissue physiology and
      pathology. Three-dimensional collagen matrices exhibit mechanical and structural
      features that resemble fibrous connective tissue and have become an important
      model system to study cell behavior in a tissue-like environment. This review
      focuses on motile and mechanical interactions between cells&#x2014;especially
      fibroblasts&#x2014;and collagen matrices. We describe several matrix contraction
      models, the interactions between fibroblasts and collagen fibrils at global and
      subcellular levels, unique features of mechanical feedback between cells and the
      matrix, and the impact of the cell-matrix tension state on cell morphology and
      mechanical behavior. We develop a conceptual framework to explain the balance
      between cell migration and collagen translocation including the concept of
      promigratory and procontractile growth factor environments. Finally, we review
      the significance of these concepts for the physiology of wound repair.

PMID- 19575668
TI  - Many paths to synaptic specificity.
AB  - The most impressive structural feature of the nervous system is the specificity
      of its synaptic connections. Even after axons have navigated long distances to
      reach target areas, they must still choose appropriate synaptic partners from the
      many potential partners within easy reach. In many cases, axons also select a
      particular domain of the postsynaptic cell on which to form a synapse. Thus,
      synapse formation is selective at both cellular and subcellular levels.
      Unsurprisingly, the nervous system uses multiple mechanisms to ensure proper
      connectivity; these include complementary labels, coordinated growth of synaptic
      partners, sorting of afferents, prohibition or elimination of inappropriate
      synapses, respecification of targets, and use of short-range guidance mechanisms
      or intermediate targets. Specification of any circuit is likely to involve
      integration of multiple mechanisms. Recent studies of vertebrate and invertebrate
      systems have led to the identification of molecules that mediate a few of these
      interactions.

PMID- 19575669
TI  - Small RNAs and their roles in plant development.
AB  - Small RNAs of 20-30 nucleotides guide regulatory processes at the DNA or RNA
      level in a wide range of eukaryotic organisms. Many, although not all, small RNAs
      are processed from double-stranded RNAs or single-stranded RNAs with local
      hairpin structures by RNase III enzymes and are loaded into argonaute-protein
      containing effector complexes. Many eukaryotic organisms have evolved multiple
      members of RNase III and the argonaute family of proteins to accommodate
      different classes of small RNAs with specialized molecular functions. Some small
      RNAs cause transcriptional gene silencing by guiding heterochromatin formation at
      homologous loci, whereas others lead to posttranscriptional gene silencing
      through mRNA degradation or translational inhibition. Small RNAs are not only
      made from and target foreign nucleic acids such as viruses and transgenes, but
      are also derived from endogenous loci and regulate a multitude of developmental
      and physiological processes. Here I review the biogenesis and function of three
      major classes of endogenous small RNAs in plants: microRNAs, trans-acting siRNAs,
      and heterochromatic siRNAs, with an emphasis on the roles of these small RNAs in
      developmental regulation.

PMID- 19575670
TI  - Trafficking to the ciliary membrane: how to get across the periciliary diffusion
      barrier?
AB  - The primary cilium organizes numerous signal transduction cascades, and an
      understanding of signaling receptor trafficking to cilia is now emerging. A
      defining feature of cilia is the periciliary diffusion barrier that separates the
      ciliary and plasma membranes. Although lateral transport through this barrier may
      take place, polarized exocytosis to the base of the cilium has been the
      prevailing model for delivering membrane proteins to cilia. Key players for this
      polarized exocytosis model include the GTPases Rab8 and Rab11, the exocyst, and
      possibly the intraflagellar tranport machinery. In turn, the sorting of membrane
      proteins to cilia critically relies on the recognition of ciliary targeting
      signals by sorting machines such as the BBSome coat complex or the GTPase Arf4.
      Finally, some proteins need to exit from cilia, and ubiquitination may regulate
      this step. The stage is now set to dissect the interplay between signaling and
      regulated trafficking to and from cilia.

PMID- 19575672
TI  - Mammalian Su(var) genes in chromatin control.
AB  - Genetic screens in Drosophila have been instrumental in distinguishing
      approximately 390 loci involved in position effect variegation and
      heterochromatin stabilization. Most of the identified genes [so-called Su(var)
      and E(var) genes] are also conserved in mammals, where more than 50 of their gene
      products are known to localize to constitutive heterochromatin. From these
      proteins, approximately 12 core heterochromatin components can be inferred. In
      addition, there are approximately 30 additional Su(var) and 10 E(var) factors
      that can, under distinct developmental options, interchange with constitutive
      heterochromatin and participate in the partitioning of the genome into repressed
      and active chromatin domains. A significant fraction of the Su(var) and E(var)
      factors are enzymes that respond to environmental and metabolic signals, thereby
      allowing both the variation and propagation of epigenetic states to a dynamic
      chromatin template. Moreover, the misregulation of human SU(VAR) and E(VAR)
      function can advance cancer and many other human diseases including more complex
      disorders. As such, mammalian Su(var) and E(var) genes and their products provide
      a rich source of novel targets for diagnosis of and pharmaceutical intervention
      in many human diseases.

PMID- 19575673
TI  - Hox genes and segmentation of the hindbrain and axial skeleton.
AB  - Segmentation is an important process that is frequently used during development
      to segregate groups of cells with distinct features. Segmental compartments
      provide a mechanism for generating and organizing regional properties along an
      embryonic axis and within tissues. In vertebrates the development of two major
      systems, the hindbrain and the paraxial mesoderm, displays overt signs of
      compartmentalization and depends on the process of segmentation for their
      functional organization. The hindbrain plays a key role in regulating head
      development, and it is a complex coordination center for motor activity,
      breathing rhythms, and many unconscious functions. The paraxial mesoderm
      generates somites, which give rise to the axial skeleton. The cellular processes
      of segmentation in these two systems depend on ordered patterns of Hox gene
      expression as a mechanism for generating a combinatorial code that specifies
      unique identities of the segments and their derivatives. In this review, we
      compare and contrast the signaling inputs and transcriptional mechanisms by which
      Hox gene regulatory networks are established during segmentation in these two
      different systems.

PMID- 19575671
TI  - Assembling neural crest regulatory circuits into a gene regulatory network.
AB  - The neural crest is a multipotent stem cell&#x2013;like population that gives
      rise to a wide range of derivatives in the vertebrate embryo including elements
      of the craniofacial skeleton and peripheral nervous system as well as
      melanocytes. The neural crest forms in a series of regulatory steps that include
      induction and specification of the prospective neural crest
      territory&#x2013;neural plate border, specification of bona fide neural crest
      progenitors, and differentiation into diverse derivatives. These individual
      processes during neural crest ontogeny are controlled by regulatory circuits that
      can be assembled into a hierarchical gene regulatory network (GRN). Here we
      present an overview of the GRN that orchestrates the formation of cranial neural
      crest cells. Formulation of this network relies on information largely inferred
      from gene perturbation studies performed in several vertebrate model organisms.
      Our representation of the cranial neural crest GRN also includes information
      about direct regulatory interactions obtained from the cis-regulatory analyses
      performed to date, which increases the resolution of the architectural circuitry
      within the network.

PMID- 19575674
TI  - Molecular circuitry of endocytosis at nerve terminals.
AB  - Presynaptic terminals are specialized compartments of neurons responsible for
      converting electrical signals into secreted chemicals. This self-renewing process
      of chemical synaptic transmission is accomplished by the calcium-triggered fusion
      of neurotransmitter-containing vesicles with the plasma membrane and subsequent
      retrieval and recycling of vesicle components. Whereas the release of
      neurotransmitters has been studied for over 50 years, the process of synaptic
      vesicle endocytosis has remained much more elusive. The advent of imaging
      techniques suited to monitor membrane retrieval at presynaptic terminals and the
      discovery of the molecules that orchestrate endocytosis have revolutionized our
      understanding of this critical trafficking event.

PMID- 19575675
TI  - Mechanisms shaping the membranes of cellular organelles.
AB  - Cellular organelles have characteristic morphologies that arise as a result of
      different local membrane curvatures. A striking example is the endoplasmic
      reticulum (ER), which consists of ER tubules with high curvature in cross
      section, peripheral ER sheets with little curvature except at their edges and the
      nuclear envelope with low curvature except where the nuclear pores are inserted.
      The ER may be shaped by several mechanisms. ER tubules are often generated
      through their association with the cytoskeleton and stabilized by two families of
      integral membrane proteins, the reticulons and DP1/Yop1p. Similar to how
      curvature is generated in budding vesicles, these proteins may use scaffolding
      and hydrophobic insertion mechanisms to shape the lipid bilayer into tubules. In
      addition, proteins of the dynamin family may deform the ER membrane to generate a
      tubular network. Mechanisms affecting local membrane curvature may also shape
      peripheral ER sheets and the nuclear envelope as well as mitochondria and
      caveolae.

PMID- 19575678
TI  - Transcriptional control of mitochondrial biogenesis and function.
AB  - Mitochondria play central roles in energy homeostasis, metabolism, signaling, and
      apoptosis. Accordingly, the abundance, morphology, and functional properties of
      mitochondria are finely tuned to meet cell-specific energetic, metabolic, and
      signaling demands. This tuning is largely achieved at the level of
      transcriptional regulation. A highly interconnected network of transcription
      factors regulates a broad set of nuclear genes encoding mitochondrial proteins,
      including those that control replication and transcription of the mitochondrial
      genome. The same transcriptional network senses cues relaying cellular energy
      status, nutrient availability, and the physiological state of the organism and
      enables short- and long-term adaptive responses, resulting in adjustments to
      mitochondrial function and mitochondrial biogenesis. Mitochondrial dysfunction is
      associated with many human diseases. Characterization of the transcriptional
      mechanisms that regulate mitochondrial biogenesis and function can offer insights
      into possible therapeutic interventions aimed at modulating mitochondrial
      function.

PMID- 19575676
TI  - Rolling cell adhesion.
AB  - Rolling adhesion on vascular surfaces is the first step in recruiting circulating
      leukocytes, hematopoietic progenitors, or platelets to specific organs or to
      sites of infection or injury. Rolling requires the rapid yet balanced formation
      and dissociation of adhesive bonds in the challenging environment of blood flow.
      This review explores how structurally distinct adhesion receptors interact
      through mechanically regulated kinetics with their ligands to meet these
      challenges. Remarkably, increasing force applied to adhesive bonds first prolongs
      their lifetimes (catch bonds) and then shortens their lifetimes (slip bonds).
      Catch bonds mediate the counterintuitive phenomenon of flow-enhanced rolling
      adhesion. Force-regulated disruptions of receptor interdomain or intradomain
      interactions remote from the ligand-binding surface generate catch bonds.
      Adhesion receptor dimerization, clustering in membrane domains, and interactions
      with the cytoskeleton modulate the forces applied to bonds. Both inside-out and
      outside-in cell signals regulate these processes.

PMID- 19575679
TI  - The functions and roles of the extracellular Ca2+-sensing receptor along the
      gastrointestinal tract.
AB  - Digestion of food and normal salt and water homeostasis in the body require a
      functional digestive tract. Recently an increasing number of studies have
      demonstrated a role for the calcium-sensing receptor along the entire
      gastrointestinal tract and its role in normal gut physiology. Detailed studies
      have been performed on colonic fluid transport and gastric acid secretion. We
      have now demonstrated that the receptor can modulate fluid secretion and
      absorption along the intestine and can thereby be a potent target to prevent
      secretory diarrhea. Recent studies have demonstrated that organic nutrients such
      as polyamines and l-amino acids can act as agonists by allosterically modifying
      the receptor. Thus, the receptor may detect nutrient availability to epithelial
      cells along the gastrointestinal tract and may be involved in the coordinated
      rapid turnover of the intestinal epithelium. Furthermore, the receptor has been
      suggested as a link for the mechanisms leading to calcium uptake by the colon and
      may thus reduce the risk for colon cancer.

PMID- 19575677
TI  - Vertebrate endoderm development and organ formation.
AB  - The endoderm germ layer contributes to the respiratory and gastrointestinal
      tracts and to all of their associated organs. Over the past decade, studies in
      vertebrate model organisms, including frog, fish, chick, and mouse, have greatly
      enhanced our understanding of the molecular basis of endoderm organ development.
      We review this progress with a focus on early stages of endoderm organogenesis
      including endoderm formation, gut tube morphogenesis and patterning, and organ
      specification. Lastly, we discuss how developmental mechanisms that regulate
      endoderm organogenesis are used to direct differentiation of embryonic stem cells
      into specific adult cell types, which function to alleviate disease symptoms in
      animal models.

PMID- 19575680
TI  - Dendritic spine dynamics.
AB  - Dendritic spines are the postsynaptic components of most excitatory synapses in
      the mammalian brain. Spines accumulate rapidly during early postnatal development
      and undergo a substantial loss as animals mature into adulthood. In past decades,
      studies have revealed that the number and size of dendritic spines are regulated
      by a variety of gene products and environmental factors, underscoring the dynamic
      nature of spines and their importance to brain plasticity. Recently, in vivo time
      lapse imaging of dendritic spines in the cerebral cortex suggests that, although
      spines are highly plastic during development, they are remarkably stable in
      adulthood, and most of them last throughout life. Therefore, dendritic spines may
      provide a structural basis for lifelong information storage, in addition to their
      well-established role in brain plasticity. Because dendritic spines are the key
      elements for information acquisition and retention, understanding how spines are
      formed and maintained, particularly in the intact brain, will likely provide
      fundamental insights into how the brain possesses the extraordinary capacity to
      learn and to remember.

PMID- 19575682
TI  - Sensing odorants and pheromones with chemosensory receptors.
AB  - Olfaction is a critical sensory modality that allows living things to acquire
      chemical information from the external world. The olfactory system processes two
      major classes of stimuli: (a) general odorants, small molecules derived from food
      or the environment that signal the presence of food, fire, or predators, and (b)
      pheromones, molecules released from individuals of the same species that convey
      social or sexual cues. Chemosensory receptors are broadly classified, by the
      ligands that activate them, into odorant or pheromone receptors. Peripheral
      sensory neurons expressing either odorant or pheromone receptors send signals to
      separate odor- and pheromone-processing centers in the brain to elicit distinct
      behavioral and neuroendocrinological outputs. General odorants activate receptors
      in a combinatorial fashion, whereas pheromones activate narrowly tuned receptors
      that activate sexually dimorphic neural circuits in the brain. We review recent
      progress on chemosensory receptor structure, function, and circuitry in
      vertebrates and invertebrates from the point of view of the molecular biology and
      physiology of these sensory systems.

PMID- 19575683
TI  - Aspirin-sensitive respiratory disease.
AB  - Aspirin-sensitive respiratory disease (ASRD) is a condition characterized by
      persistent and often severe inflammation of the upper and lower respiratory
      tracts. Patients develop chronic eosinophilic rhinosinusitis, nasal polyposis,
      and asthma. The ingestion of aspirin and other cyclooxygenase-1 (COX-1)
      inhibitors induces exacerbations of airway disease that may be life-threatening.
      Thus, aspirin sensitivity is a phenotypic marker for the syndrome, yet nearly all
      affected individuals can be desensitized by the administration of graded doses of
      aspirin, leading to long-term clinical benefits. Patients with aspirin
      sensitivity are often able to tolerate selective COX-2 inhibitors. The
      pathogenesis of ASRD is underpinned by abnormalities in eicosanoid biosynthesis
      and eicosanoid receptor expression coupled with intense mast cell and
      eosinophilic infiltration of the entire respiratory tract. This review focuses on
      the molecular, cellular, and biochemical abnormalities characterizing ASRD and
      highlights unanswered questions in the literature and potential future areas of
      investigation.

PMID- 19575681
TI  - Endocannabinoid signaling and long-term synaptic plasticity.
AB  - Endocannabinoids (eCBs) are key activity-dependent signals regulating synaptic
      transmission throughout the central nervous system. Accordingly, eCBs are
      involved in neural functions ranging from feeding homeostasis to cognition. There
      is great interest in understanding how exogenous (e.g., cannabis) and endogenous
      cannabinoids affect behavior. Because behavioral adaptations are widely
      considered to rely on changes in synaptic strength, the prevalence of eCB
      mediated long-term depression (eCB-LTD) at synapses throughout the brain merits
      close attention. The induction and expression of eCB-LTD, although remarkably
      similar at various synapses, are controlled by an array of regulatory influences
      that we are just beginning to uncover. This complexity endows eCB-LTD with
      important computational properties, such as coincidence detection and input
      specificity, critical for higher CNS functions like learning and memory. In this
      article, we review the major molecular and cellular mechanisms underlying eCB
      LTD, as well as the potential physiological relevance of this widespread form of
      synaptic plasticity.

PMID- 19575684
TI  - Immunobiology of asthma.
AB  - Asthma is characterized by chronic inflammation of the airways in which there is
      an overabundance of eosinophils, mast cells, and activated T helper lymphocytes.
      These inflammatory cells release mediators that then trigger bronchoconstriction,
      mucus secretion, and remodeling. The inflammatory mediators that drive this
      process include cytokines, chemokines, growth factors, lipid mediators,
      immunoglobulins, and histamine. The inflammation in allergic asthma can be
      difficult to control. This is mainly due to the development of an adaptive
      immunity to an allergen, leading to immunological memory. This leads to recall
      reactions to the allergen, causing persistent inflammation and damage to the
      airways. Generally, in asthma inflammation is directed by Th2 cytokines, which
      can act by positive feedback mechanisms to promote the production of more
      inflammatory mediators including other cytokines and chemokines. This review
      discusses the role of cytokines and chemokines in the immunobiology of asthma and
      attempts to relate their expression to morphological and functional abnormalities
      in the lungs of asthmatic subjects. We also discuss new concepts in asthma
      immunology, in particular the role of cytokines in airway remodeling and the
      interaction between cytokines and infection.

PMID- 19575685
TI  - Short-term natural history of the standard approaches for gastrostomy tube
      placement in the pediatric patient.
AB  - INTRODUCTION: Gastrostomy placement is a common procedure in the pediatric
      population. Standard approaches of tube placement include open, laparoscopic, and
      percutaneous endoscopic methods. Placement of the gastrostomy in relation to the
      fundus and the anterior abdominal wall is crucial to ensure adequate comfort and
      functionality. Misplacement may require repositioning of the gastrostomy, the
      rate of which has not been well documented. We, therefore, have reviewed a multi
      institutional experience with gastrostomy tube placement to determine the short
      term natural history of placement, based on approach, and to establish a cohort
      to determine the long-term natural history. METHODS: We conducted a retrospective
      review of all pediatric patients who underwent percutaneous endoscopic,
      laparoscopic, or open gastrostomy placement at two institutions from 2000 to
      2008. RESULTS: There were a total of 1534 patients who underwent gastrostomy tube
      placement during this time period. The most common procedure was fundoplication
      with gastrostomy (N = 832), followed by gastrostomy alone (N = 420), and then
      percutaneous endoscopic gastrostomy (PEG) (N = 285). There were 4 (0.3%)
      gastrostomy tubes that required repositioning to a new site due to encroachment
      upon the rib margin. Two were open and 2 were PEG (P > 0.99). Twenty of 39
      patients who had an open fundoplication following gastrostomy had the gastrostomy
      taken down during the procedure, compared to 5 of 31 patients (P = 0.03), who
      underwent laparoscopic fundoplication following gastrostomy. CONCLUSIONS: These
      data demonstrate that the need for gastrostomy tube repositioning is rare in the
      short term, regardless of approach, although a takedown of the gastrostomy is
      more likely when an open fundoplication is performed.

PMID- 19575686
TI  - Outcome of stoma closure in children: a comparison of laparoscopy-assisted and
      conventional open techniques.
AB  - Laparoscopy-assisted stoma closure (LASC; n = 28) and conventional open closure
      (CSC; n = 24) were compared by assessing outcome in 52 consecutive cases of stoma
      closure (SC) in children.

PMID- 19575687
TI  - The relationship between gravidity and parity and colorectal cancer risk.
AB  - OBJECTIVES: The influence of hormonal changes caused by pregnancy has been well
      studied in relation to colorectal cancer risk, but the association remains
      undefined. The purpose of this investigation was to examine in a case-control
      study the relationship between differences in gravidity and parity and colorectal
      cancer risk and if the association varied by microsatellite instability (MSI), a
      feature more common in women. METHODS: The study population included incident
      colorectal cancer patients (n = 1014), aged 50-74 years, diagnosed in 1998-2002
      in Washington state and controls (n = 1064) randomly selected from population
      lists. All study subjects completed telephone interviews to ascertain prior
      pregnancies, live births, and other covariates. Case tissue samples were obtained
      for MSI analyses. Multivariable logistic regression models estimated odds ratios
      (OR) and 95% confidence intervals (CI), adjusting for age, family history of
      colorectal cancer, body mass index (BMI), education, endoscopy screening, oral
      contraceptive use, hormone therapy use, smoking, and alcohol consumption.
      RESULTS: There was an approximate 30%-50% reduction in risk of colon cancer
      associated with gravidity, which was attenuated in the analysis with parity.
      Increasing gravidity and parity were associated with a suggestion of a decreasing
      trend in risk for rectal cancer (p for trend = 0.07). Compared with women who had
      equal numbers of pregnancies and live births, women who were nulligravid and
      nulliparous had a 40%-60% increased risk of colon cancer. There was a suggestion
      of a reduced risk of both colon and rectal cancer associated with one more
      pregnancy than live birth. There was a suggestion of an increased risk of MSI
      high tumors with nulligravidity and nulliparity. CONCLUSIONS: These results
      confirm the importance of pregnancy events in the etiology of colon and rectal
      cancer.

PMID- 19575688
TI  - Performance characteristics of postpartum screening tests for type 2 diabetes
      mellitus in women with a history of gestational diabetes mellitus: a systematic
      review.
AB  - BACKGROUND: Women with a history of gestational diabetes mellitus are at high
      risk for type 2 diabetes mellitus. We systematically reviewed and synthesized the
      literature on the sensitivity, specificity, and reproducibility of postpartum
      screening tests for type 2 diabetes in women with prior gestational diabetes to
      inform screening guidelines. METHODS: We searched electronic databases through
      October 1, 2008. Two investigators independently reviewed titles, abstracts, and
      articles, performed serial data abstraction, and independently assessed quality.
      We calculated standard errors and confidence intervals for sensitivity and
      specificity using the exact binomial formula. RESULTS: Eleven studies contained
      13 evaluations of a comparison screening test with the 2-h 75-g oral glucose
      tolerance test (OGTT) reference. All studies used a cross-sectional study design.
      There were ten comparisons of a single fasting blood glucose (FBG) >=7.0 mmol/L
      (>=126 mg/dL) with the OGTT. The sensitivity ranged from 14%-100% in five studies
      using the 1985 World Health Organization's (WHO) criteria as the reference and
      from 16%-89% in five studies using the 1999 WHO criteria as the reference.
      Variation in the sensitivities may be due to the limited number of comparisons,
      differences in populations, and timing of screening. There were high losses to
      follow-up, limiting generalizability. CONCLUSIONS: When compared with the OGTT,
      the single FBG alone was not consistently reported to be a sensitive screening
      test for type 2 diabetes in women with a history of gestational diabetes.
      Longitudinal studies are needed to address the natural history of glucose
      metabolism in women with a history of gestational diabetes, the optimal approach
      to diagnostic testing for type 2 diabetes in this population, and the short-term
      and long-term outcomes of testing.

PMID- 19575689
TI  - Acceptability of a carrageenan-based candidate vaginal microbicide and matching
      placebo: findings from a phase II safety trial among women in Chiang Rai,
      Thailand.
AB  - OBJECTIVE: To evaluate extended acceptability of vaginal use of a carrageenan
      based candidate microbicide and placebo in northern Thai women. METHODS: As part
      of a randomized, placebo-controlled, triple-blinded clinical trial, women were
      asked to insert gel with each vaginal sex act and at least three times per week
      for 1 year. Used applicators were collected monthly; acceptability questions were
      asked quarterly. RESULTS: One hundred sixty-five women were enrolled (83
      microbicide, 82 placebo); 148 (90%) remained in the study for 12 months. Gel use
      was high, with > or =87% returning at least three used applicators per week at
      each visit. Although acceptability was generally high, some decline in positive
      reporting was noted in terms of ease of application, timing of gel insertion, and
      gel volume over time. Approximately one quarter reported gel use increased her
      sexual pleasure. Over one quarter reported that gel volume of 5 mL was too much.
      All women with a steady partner at 12 months reported talking to their partner
      about using the gel. Only 2 women spontaneously mentioned being able to use a
      product covertly as one of the most appealing attributes of a potential
      microbicide. CONCLUSIONS: Although women in this study generally reported high
      acceptability and use, some found 5 mL of gel to be too much. Focusing on
      enhanced sexual pleasure and lubrication may be beneficial for marketing proven
      microbicides. Development of products will need to balance lubrication and
      efficacy with perceptions of too much volume. The ability to use a product
      covertly was not a high priority in this population.

PMID- 19575690
TI  - Sleep and health consequences of shift work in women.
AB  - Women constitute about half the work force, and women shift workers warrant
      special attention given the different physiological needs of women, their
      reproductive status, and the added burden of family responsibilities. There is
      increasing evidence that women have greater difficulty adjusting to shift work
      compared to their male counterparts and that sleep problems may in large part
      account for this difficulty. The purpose of this article is to review the
      existing literature to highlight the differential negative impact of shift work
      on sleep and other health issues in women and as part of a needs assessment to
      promote research in female shift workers by developing and prioritizing research
      questions in this field. The literature suggests that women shift workers report
      poor sleep quality and experience reproductive disturbances, an increased risk of
      breast cancer, and a greater risk of metabolic and cardiovascular disorders.

PMID- 19575691
TI  - Considerations for the definition, measurement, consequences, and prevention of
      dating violence victimization among adolescent girls.
AB  - Violence experienced by adolescent girls from their dating partners poses
      considerable threat to their health and well-being. This report provides an
      overview of the prevalence and consequences of heterosexual teen dating violence
      and highlights the need for comprehensive prevention approaches to dating
      violence. We also discuss some considerations and future directions for the study
      and prevention of dating violence. We begin with a discussion of the definition
      of dating violence and also discuss measurement concerns and the need for
      evaluation of prevention strategies. Although women and men of all ages may be
      the victims or perpetrators, male-to-female dating violence experienced by
      adolescent girls is the main focus of this article. We incorporate research
      regarding girls' perpetration of dating violence where appropriate and as it
      relates to prevention.

PMID- 19575692
TI  - Safety of holmium laser enucleation of the prostate in anticoagulated patients.
AB  - PURPOSE: Oral anticoagulation (OA) is considered a strict contraindication to
      transurethral resection of the prostate (TURP). In recent years, however, safe
      and effective surgical alternatives such as holmium laser enucleation of the
      prostate (HoLEP) have emerged. Evidence from randomized trials has revealed that
      HoLEP has fewer bleeding complications than TURP, suggesting that HoLEP in
      anticoagulated patients is safer than TURP. However, published data evaluating
      bleeding complications in anticoagulated patients undergoing HoLEP are
      incomplete. Using a retrospective design, this is the first study to compare the
      bleeding complication rates of anticoagulated patients undergoing HoLEP to
      patients not on OA. MATERIALS AND METHODS: We reviewed the electronic medical
      records of the first 76 HoLEP patients treated by a single urologist in two New
      England hospitals from May 2002 to September 2007. RESULTS: Thirty-nine were on
      OA, and 37 were controls. Thirteen patients were on coumadin (mean international
      normalized ratio [INR] 1.5), and 25 were on aspirin at the time of their surgery.
      Among the patients on OA, 8% (n = 2) had intraoperative hematuria compared to 14%
      (n = 5) of controls (p = 0.25). No patients in either group required blood
      transfusions. Stratifying the OA population revealed no statistical differences
      in bleeding complication rates between the coumadin, aspirin, and control groups
      (p = 0.34). Additionally, there were no differences in standard postoperative
      outcomes. CONCLUSION: These findings suggest that HoLEP has excellent hemostatic
      properties in high-risk patients and is a safe surgical alternative to TURP in
      patients on OA.

PMID- 19575694
TI  - Carrier proteins for fusion expression of antimicrobial peptides in Escherichia
      coli.
AB  - Antimicrobial peptides are an essential component of innate immunity and play an
      important role in host defence against microbial pathogens. They have received
      increasing attention recently as potential novel pharmaceutical agents. To meet
      the requirement for necessary basic science studies and clinical trials, large
      quantities of these peptides are needed. In general, isolation from natural
      sources and chemical synthesis are not cost-effective. The relatively low cost
      and easy scale-up of the recombinant approach renders it the most attractive
      means for large-scale production of antimicrobial peptides. Among the many
      systems available for protein expression, Escherichia coli remains the most
      widely used host. Antimicrobial peptides produced in E. coli are often expressed
      as fusion proteins, which effectively masks these peptides' potential lethal
      effect towards the bacterial host and protects the peptides from proteolytic
      degradation. Although some carriers confer peptide solubility, others promote the
      formation of inclusion bodies. The present minireview considers the most commonly
      used carrier proteins for fusion expression of antimicrobial peptides in E. coli.
      The favourable properties of SUMO (small ubiquitin-related modifier) as a novel
      fusion partner are also discussed.

PMID- 19575693
TI  - Evaluation of the relationship between hyperinsulinaemia and myocardial
      ischaemia/reperfusion injury in a rat model of depression.
AB  - Major depression is associated with medical co-morbidity, such as ischaemic heart
      disease and diabetes, but the underlying pathophysiological mechanisms remain
      unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of
      depression exhibiting features similar to those of depressed individuals. The aim
      of the present study was to compare the myocardial responsiveness to I/R
      (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning)
      in hearts from FSL rats using SD (Sprague-Dawley) rats as controls and to
      characterize differences in glucose metabolism and insulin sensitivity between
      FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected
      or not to IPC before 40 min of global ischaemia, followed by 120 min of
      reperfusion. Myocardial infarct size was found to be significantly larger in the
      FSL rats than in the SD rats following I/R injury (62.4+/-4.2 compared with
      46.9+/-2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved
      haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference
      was found in blood glucose levels between the two groups measured after 12 h of
      fasting, but fasting plasma insulin (70.1+/-8.9 compared with 40.9+/-4.7 pmol/l;
      P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were
      significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats
      had larger infarct sizes following I/R injury and were found to be
      hyperinsulinaemic compared with SD rats, but appeared to have a maintained
      cardioprotective mechanism against I/R injury, as IPC reduced infarct size in
      these rats. This animal model may be useful in future studies when examining the
      mechanisms that contribute to the cardiovascular complications associated with
      depression.

PMID- 19575696
TI  - Computed tomography - spiralling towards diagnosis.

PMID- 19575697
TI  - Diagnostic accuracy of positive contrast computed tomography arthrography for the
      detection of injuries to the medial meniscus in dogs with naturally occurring
      cranial cruciate ligament insufficiency.
AB  - OBJECTIVE: To assess the usefulness of computed tomography arthrography of the
      stifle in diagnosing meniscal tears in dogs with cranial cruciate ligament
      insufficiency. METHODS: A prospective clinical study was performed. Dogs were
      included if they had evidence of cranial cruciate ligament insufficiency or
      persistent or recurrent lameness following surgery for cranial cruciate ligament
      insufficiency. Dogs were sedated for a computed tomography scan of the affected
      stifle, orientated in the dorsal plane. A survey computed tomography scan was
      followed by a computed tomography arthrogram. A stifle arthrotomy was performed,
      and the surgical findings were recorded. The computed tomography scans were
      reviewed by three blinded reviewers, and the results were compared to the
      surgical findings. RESULTS: Twenty-one computed tomography arthrograms from 20
      dogs were included. At surgery, damage to the medial meniscus was identified in
      14 stifles. Initial interpretation of computed tomography arthrography images was
      57 to 64 per cent sensitive and 71 to 100 per cent specific for diagnosing medial
      meniscal injuries. Interpretation of the images on retrospective analysis was 71
      per cent sensitive and 100 per cent specific, with an accuracy of 0.857. CLINICAL
      SIGNIFICANCE: The accuracy of stifle computed tomography arthrography for the
      diagnosis of tears to the medial meniscus was found to be good. It is a minimally
      invasive and repeatable technique, which does not require general anaesthesia or
      specialist training to obtain the images. The ability to reliably diagnose
      meniscal injury without the need for surgery may be advantageous, particularly in
      dogs which had previously had surgery for cranial cruciate ligament
      insufficiency.

PMID- 19575698
TI  - Computed tomographic and magnetic resonance imaging features of canine segmental
      caudal vena cava aplasia.
AB  - OBJECTIVE: To describe the computed tomographic and magnetic resonance imaging
      features of segmental caudal vena cava aplasia and associated vascular anomalies
      in dogs. METHODS: A retrospective study was performed reviewing computed
      tomographic and magnetic resonance imaging archives of eight institutions for
      dogs with segmental caudal vena cava aplasia. Inclusion criteria included a
      computed tomographic or magnetic resonance imaging study and supportive
      diagnostic and follow-up information. Abdominal vessels were reviewed for size,
      shape, location and course (including tributaries and branches) and classified as
      normal, abnormal or shunt vessels. RESULTS: Ten dogs with segmental caudal vena
      cava aplasia were identified. In all dogs, postrenal caval blood was shunted to
      either a right or a left azygos vein, with seven different angiographic patterns.
      Affected dogs were predominantly female (70 per cent) and young (mean 2.6 years).
      Additional portocaval and porto-azygos shunt vessels were identified in two cases
      each. Computed tomographic angiography and magnetic resonance angiography
      depicted details of abdominal vessels including thrombus formation in one dog.
      CLINICAL SIGNIFICANCE: Segmental caudal vena cava aplasia is a vascular
      congenital anomaly in the dog that can be associated with thrombosis and
      portosystemic shunts. Computed tomographic angiography and magnetic resonance
      angiography are excellent tools to demonstrate the complex vascular anatomy and
      to guide treatment planning for portosystemic shunts and thrombolytic therapy.

PMID- 19575699
TI  - Intraoperative use of a reflective blanket (Sirius rescue sheet) for temperature
      management in dogs less than 10 kg.
AB  - OBJECTIVES: To compare the effects of the Sirius rescue sheet with gel pads
      versus gel pads alone on intraoperative body temperature in dogs less than 10 kg.
      METHODS: Forty small breed dogs undergoing elective surgical procedures were
      randomly assigned to two groups. One group was intraoperatively laid on warmed
      gel pads, and the other group was additionally wrapped in a Sirius rescue sheet.
      Oesophageal body temperature was determined every 10 minutes and compared between
      groups. Temperature of gel pads was measured preoperatively and postoperatively
      to compare heat loss of the gel pads between groups. RESULTS: The body
      temperature of dogs wrapped with the Sirius rescue sheet increased
      intraoperatively. In dogs just lying on warmed gel pads, a decrease in mean body
      temperature was revealed and mean body temperatures differed between groups after
      40 minutes. Extent of heat loss from the gel pads did not differ between the
      groups. CLINICAL SIGNIFICANCE: The Sirius rescue sheet, used in addition to
      warmed gel pads, led to higher intraoperative body temperatures in small breed
      dogs undergoing surgical procedures to the extremities and the head. The cost
      effectiveness and ease of handling make this a useful addition to clinical
      practice.

PMID- 19575700
TI  - Soft palate hypoplasia and concurrent middle ear pathology in six dogs.
AB  - This retrospective clinical study describes six consecutive cases of bilateral
      hypoplasia/malformation of the soft palate in dogs in which associated middle ear
      disease was investigated and the palatine defects were surgical repaired.
      Radiographic abnormalities of the tympanic bullae were seen in both ears of all
      six dogs (12 of 12). Negative tympanocentesis findings were recorded in 11 of 12
      ears. A purulent otitis media was confirmed in one ear of one dog, and loss of
      hearing was also demonstrated in this ear on brainstem auditory evoked response
      hearing assessment. There was no evidence of hearing loss on brainstem auditory
      evoked response in any of the remaining ears. Surgical repair of the soft palate
      defect was undertaken in all six dogs. Long-term assessment of the clinical
      outcome was considered excellent in five dogs and reasonable in one dog (mean 18
      months, range seven to 27 months). It would appear that surgical intervention for
      the treatment of bilateral palatine malformation/hypoplasia may be associated
      with a better prognosis than reported previously. The lack of middle ear effusion
      and associated hearing impairment suggests that the underlying aetiology of
      middle ear pathology in dogs suffering from congenital palatine defects may be
      different from that observed in human beings. The true nature of the radiographic
      bullae changes seen in dogs with soft palate defects remains unclear.

PMID- 19575701
TI  - A case of multiple unilateral corneal epithelial inclusion cysts in a dog.
AB  - A three-year-old neutered female Labrador cross was presented for investigation
      of two corneal epithelial inclusion cysts affecting the left eye. The
      aetiopathogenesis of the cyst formation was suspected to be traumatic. The cysts
      were removed successfully by superficial keratectomy, followed by a third eyelid
      flap. Histologically, both lesions were represented by cystic formations lined
      with multi-layered squamous epithelium, consistent with stromal inclusion of
      surface corneal epithelium. Complete recovery was achieved, and there was no
      recurrence at six month follow-up.

PMID- 19575703
TI  - Incorrect comments regarding the use of butorphanol-medetomidine as a premedicant
      in cats.

PMID- 19575705
TI  - Hand washing and puerperal fever.

PMID- 19575706
TI  - NgR RNA interference, combined with zymosan intravitreal injection, enhances
      optic nerve regeneration.
AB  - Mature retinal ganglion cells like other CNS neurons are unable to regenerate
      their axons after injury. Regenerative failure has been attributed, in part, to
      two factors: the existence of myelin-derived inhibitors that bind to the Nogo
      receptor (NgR) and a deficiency of trophic support factors. We investigated the
      regrowth of injured axons both by inhibiting NgR by RNA interference and by
      recruiting exogenous trophic support by zymosan intravitreal injection. Our
      results showed that either approach can stimulate optic nerve axon regrowth but
      regenerated axons can grow longer and extend further when both methods are
      combined. We conclude that endogenous NgR inhibition and exogenous trophic
      support both play independent, important roles in enhancing optic nerve axon
      regrowth and that the regenerative effect can be augmented when the two are
      combined. This may provide a therapeutic strategy for promoting axon regeneration
      in the CNS as well.

PMID- 19575709
TI  - Education and professional development.

PMID- 19575707
TI  - Interleukin-10 provides direct trophic support to neurons.
AB  - Interleukin (IL)-10, a prototypical anti-inflammatory cytokine, has been shown to
      provide beneficial effects in neuronal injury in vivo but the full range of
      actions has not been established. In order to understand the neuronal mechanisms
      underlying IL-10-mediated neuroprotection, we examined the effect of IL-10 on
      primary neurons in culture. We found that IL-10 exerted a direct trophic
      influence on spinal cord neurons, and that activation of the neuronal IL-10
      receptor provided trophic support and survival cues to overcome the neurotoxic
      effects of glutamate in vitro. IL-10 treatment resulted in activation of janus
      associated kinases/signal transducers and transcription factors and
      phosphatidylinositol 3-kinase-AKT pathways in neurons to enhance expression of
      Bcl-2 and Bcl-x(L); under stress conditions IL-10 blocks cytochrome c release and
      caspase cleavage. IL-10 activation of the canonical nuclear factor kappaB pathway
      enhanced translocation of p50 and p65 and enhanced their binding to kappaB DNA
      sequences, with p50 playing a more prominent role in neuronal survival. These
      data indicate that in addition to known anti-inflammatory effects through
      astroglia in other inflammatory cells, IL-10 has direct neuronal effects with
      important implications for development and neuroprotection.

PMID- 19575708
TI  - Insulin receptor signaling regulates actin cytoskeletal organization in
      developing photoreceptors.
AB  - The insulin receptor (IR) and IR signaling proteins are widely distributed
      throughout the CNS. IR signaling provides a trophic signal for transformed
      retinal neurons in culture and we recently reported that deletion of IR in rod
      photoreceptors by Cre/lox system resulted in stress-induced photoreceptor
      degeneration. These studies suggest a neuroprotective role of IR in rod
      photoreceptor cell function. However, there are no studies available on the role
      of insulin-induced IR signaling in the development of normal photoreceptors. To
      examine the role of insulin-induced IR signaling, we analyzed cultured neuronal
      cells isolated from newborn rodent retinas. In insulin-lacking cultures,
      photoreceptors from wild-type rat retinas exhibited an abnormal morphology with a
      wide axon cone and disorganization of the actin and tubulin cytoskeleton.
      Photoreceptors from IR knockout mouse retinas also exhibited a similar abnormal
      morphology. A novel finding in this study was that addition of docosahexaenoic
      acid, a photoreceptor trophic factor, restored normal axonal outgrowth in insulin
      lacking cultures. These data suggest that IR signaling pathways regulate actin
      and tubulin cytoskeletal organization in photoreceptors; they also imply that
      insulin and docosahexaenoic acid activate at least partially overlapping
      signaling pathways that are essential for the development of normal
      photoreceptors.

PMID- 19575710
TI  - The times they are a changin.
AB  - AIM: A discussion paper outlining the potential for a multi-qualified health
      practitioner who has undertaken a programme of study incorporating the strengths
      of the specialist nurse with other professional routes. BACKGROUND AND RATIONALE:
      The concept and the context of 'nursing' is wide and generalized across the
      healthcare spectrum with a huge number of practitioners in separate branches,
      specialities and sub-specialities. As a profession, nursing consists of different
      groups in alliance with each other. How different is the work of the mental
      health forensic expert from an acute interventionalist, or a nurse therapist,
      from a clinical expert in neurological deterioration? The alliance holds because
      of the way nurses are educated and culturalized into the profession, and the
      influence of the statutory bodies and the context of a historical nationalized
      health system. This paper discusses the potential for a new type of healthcare
      professional, one which pushes the intra- and inter-professional agenda towards
      multi-qualified staff who would be able to work across current care boundaries
      and be more flexible regarding future care delivery. In September 2003, the
      Nursing and Midwifery Council stated that there were 'more than 656 000
      practitioners' on its register and proposed that from April 2004, there were new
      entry descriptors. Identifying such large numbers of practitioners across a wide
      range of specialities brings several areas of the profession into question. Above
      all else, it highlights how nursing has fought and gained recognition for
      specialisms and that through this, it may be argued client groups receive the
      best possible 'fit' for their needs, wants and demands. However, it also
      highlights deficits in certain disciplines of care, for example, in mental health
      and learning disabilities. We argue that a practitioner holding different
      professional qualifications would be in a position to provide a more holistic
      service to the client. Is there then a gap for a 'new breed' of practitioner; 'a
      hybrid' that can achieve a balanced care provision to reduce the stress of
      multiple visits and multiple explanations? METHODS: Review of the literature but
      essentially informed by the authors personal vision relating to the future of
      health practitioner education. IMPLICATIONS FOR NURSING MANAGEMENT: This article
      is of significance for nurse managers as the future workforce and skill mix of
      both acute and community settings will be strongly influenced by the initial
      preregistration nurse education.

PMID- 19575711
TI  - Delphi survey of research priorities.
AB  - AIM: To identify nurses' priorities for topics and issues to be addressed by a
      developing nursing research program at a county hospital. BACKGROUND: Delphi
      surveys have been effective at other hospitals to identify research priorities of
      nurses. METHODS: A Delphi survey was performed in two rounds. Questionnaires were
      distributed to all 415 nurses who worked at the hospital. RESULTS: A total of 274
      nurses returned the Round I questionnaire (response rate, 66%), and 249 returned
      the Round II questionnaire (response rate, 60%). CONCLUSIONS: The Delphi survey
      was successfully used to identify nurses' research priorities at a county
      hospital. A total of 39 topics were identified from content analysis of research
      areas described by nurses. Factor analysis revealed three factors: work
      environment, newborn issues and effects of leadership. IMPLICATIONS FOR NURSING
      MANAGEMENT: The Delphi survey is a useful way to begin a program of research.
      Nurses who have a successful experience with research are more likely to become
      further involved in research, which will allow them to more effectively
      participate in decision making and improving the work environment. In addition,
      items were identified that needed to be addressed by nursing managers.

PMID- 19575712
TI  - Evaluating a preceptorship programme in South West Ireland: perceptions of
      preceptors and undergraduate students.
AB  - AIM: The study sought to evaluate stakeholder perspective of preceptor
      preparation and attributes. BACKGROUND: In Ireland, undergraduate students are
      supported by a named preceptor on clinical placement. A preceptor is a registered
      nurse who has completed a teaching, assessment and preceptorship programme.
      Preceptor preparation is costly in terms of facilitation and staff
      release/replacement. To date, in Ireland, research has not explored the
      effectiveness of preceptor preparation. METHOD: An utilization-focussed approach
      was adopted incorporating a two-phase research process; Phase 1 being exploratory
      while Phase 2 aimed to validate inductions derived from the previous stage.
      Results The programme is effective in meeting its learning outcomes. The findings
      are categorized into four theme areas: the importance of preceptor
      characteristics, the demonstration of these characteristics, knowledge
      demonstrated by the preceptors and the skills demonstrated by the preceptor.
      CONCLUSION(S): Preceptors, to be effective within the preceptor/student
      relationship, need to integrate both their professional and personal attributes
      to effectively socialize students to the profession of nursing. IMPLICATIONS FOR
      NURSING MANAGEMENT: The preceptor role is invaluable within nurse education. This
      study supports the release of registered nurses to attend preceptor preparation
      programmes. It highlights the importance of nursing management in preceptor
      selection, release, support and monitoring in order to create an effective
      clinical learning environment.

PMID- 19575713
TI  - Implementing graduate entry registration for nursing in England: a scope review.
AB  - AIMS: A graduate entry workforce for nurse registration has been approved for
      England by 2010/11. The aim of this research was to discover the immediate tasks
      facing nurse managers in implementing that change. Previous research has focused
      on making the case for change rather than on implementation. BACKGROUND: Similar
      to the implementation of Project 2000, this change in nurse education and
      employment will raise questions for employers and for higher education
      institutions. It will also raise questions about nurse recruitment numbers,
      workforce development, and the profiles of entrants to a changing workforce.
      METHOD: In preparation for these changes, we conducted a scope review of
      published and grey literature in the English language. We also reviewed the
      earlier experiences of transfer to graduate status amongst other workforces such
      as teaching and social work and we investigated reported practice in other
      industrialised countries. RESULTS: The education provider changes necessary for
      such a large professional workforce will need considerable leadership skills from
      within nursing and nurse management. At present, there are too many employers and
      education providers in England who appear to be relatively unaware of the changes
      facing nurse education and professional practice and the urgency needed to lead
      that change. CONCLUSIONS: Education, training and development as well as
      employer/commissioner practice will rely on leadership from within the nurse
      profession itself. For nurse managers, this requires a rapid planning process in
      order to ensure smooth implementation. The danger is that either education
      providers or commissioners of nursing services will react rather than proactively
      plan for the changes that are already in progress.

PMID- 19575714
TI  - What should we assess in practice?
AB  - AIM: This article reports on a PhD study and follow up work undertaken to review
      and develop a tool for assessment of practice. BACKGROUND: The assessment of
      practice in nursing and midwifery education and, other health professions has
      been the source of concern, criticism and research for a number of years with the
      conclusion that it might not be possible to develop an assessment tool that could
      encompass all aspects of professional practice. METHODS: A qualitative evaluation
      study was undertaken using the naturalistic method of inquiry. A combination of
      tools was used in order to collect the data and enable progressive focusing and
      cross checking of the findings. These included documentary analysis, a
      questionnaire and focus group and individual interviews. The data was collected
      from documents analysis, focus group interviews, individual interviews and
      questionnaires. RESULTS: The results showed that the assessment tool in use at
      the time did not encompass all criteria assessors used and six areas were
      identified as those to include in any future tool. CONCLUSION: The six areas
      identified by subjects as those to include in any assessment tool were further
      developed with specific statements so that they could be used within a tool.
      IMPLICATIONS FOR NURSING MANAGEMENT AND EDUCATION: Within the changing nature of
      health care there is a need to review whether the tool used for assessing pre
      registration education of nursing and midwifery students practice is 'fit for
      purpose'.

PMID- 19575715
TI  - Nursing first year of practice, past, present and future: documenting the journey
      in New Zealand.
AB  - AIM: Documenting the journey of graduate nurse support in New Zealand from local
      programmes to a nationally consistent framework. BACKGROUND: Education of nurses
      in New Zealand has changed over the decades, from apprenticeship-style hospital
      based training to academically prepared registered nurses. Newly graduated nurses
      require time to become confident within the clinical setting. To achieve this, a
      well-supported graduate nurse programme is required. EVALUATION: The authors
      utilized historical reviews of nursing education within New Zealand and current
      work being undertaken by a national working party to implement a nationally
      consistent graduate nurse programme. KEY ISSUES: Disparity between locally
      delivered graduate programmes. Lack of funding to provide a well-structured
      programme and the impact on the recruitment and retention of new nurses.
      CONCLUSIONS: It was identified that there was a strong need to ensure graduate
      nurse programmes were consistent across New Zealand in order to support graduate
      nurses and retain them in the workforce. IMPLICATIONS FOR NURSING: management The
      first year of practice remains a challenging transition time with a need for a
      well-structured and supported programme. Key needs include learning activities
      grounded in practice experience, robust programme coordination, skilled clinical
      educators, preceptors, and a structured learning framework.

PMID- 19575716
TI  - The development and evaluation of a succession planning programme in nursing, in
      Australia.
AB  - AIM: This study reports on a locally organized model of succession planning in a
      550-bed general hospital. BACKGROUND: Within healthcare, succession planning has
      traditionally been considered for people at the executive director level and
      little research has been published with nurses working at the clinical level.
      METHOD: A succession planning model was developed from the literature and through
      a process of consultation with senior staff. The model was then evaluated from a
      customer satisfaction, programme progress, effective placement and organizational
      results perspectives. Nurses who were successful in obtaining a new role were
      surveyed after 6 weeks in the position. Descriptive statistics, including numbers
      of placements and types of positions filled, were recorded. A checklist for
      conducting a programme evaluation of succession planning was also used. RESULTS:
      Twenty-five nurses participated, with 31 positions succeeded to. Nurses reported
      positively that the programme was beneficial, increased their sense of career
      planning and gave them a greater understanding of their career pathway.
      CONCLUSIONS: The succession planning programme provided an opportunity for the
      organization to identify new leaders. The study outcomes have identified
      potential improvements to the way succession planning is conducted at the
      hospital. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse Managers are in key
      positions to develop effective succession planning models. This study offers a
      process for managers to develop effective succession planning programmes within
      their organization.

PMID- 19575717
TI  - The management of advanced practitioner preparation: a work-based challenge.
AB  - AIMS: This paper explores the collaborative development of a Master's level
      advanced practice programme in the context of the radical reform and remodelling
      of the UK's National Health Service. Some of the educational, managerial and
      practice challenges are discussed. BACKGROUND: Changes to education and training
      in response to key strategic reviews undertaken by the Greater Manchester
      Strategic Health Authority (North West of England) established a need to develop
      nurses and allied health care practitioners to advanced practitioner level. This
      paper considers how employers, commissioners and educationalists worked together
      to produce a Master's level programme to prepare nurses and other health care
      practitioners for sustainable advanced practice roles. KEY ISSUES: Developing
      innovative and effective curricula to meet the needs of post graduate students
      from varied backgrounds preparing to practice in different contexts with
      different client groups is challenging. However, the development of individual
      learning pathways and work-based learning ensures that the student's work and
      intended advanced practice role remains at the centre of their learning. Analysis
      of each student's knowledge and skill deficits alongside an analysis of the
      organization's readiness to support them as qualified advanced practitioners
      (APs) is instrumental in ensuring that organizations are ready to support
      practitioners in new roles. CONCLUSION: Work-based learning and collaboration
      between students, employers and higher education institutions can be used to
      enable managers and students to unravel the network of factors which affect
      advanced practice in health and social care. Additionally, collaborative working
      can help to create opportunities to develop strategies that will facilitate
      change. Implications for nursing management Sustainable change concerned with the
      introduction of advanced practitioner roles present a real challenge for managers
      at a strategic and operational level. Commissioning flexible, collaborative and
      service-led educational programmes can assist in ensuring that change is
      sustainable and produce practitioners who are fit for practice, purpose and
      award.

PMID- 19575718
TI  - Twenty-four hour care: implications for the role and developmental needs of
      nurses in acute and community settings.
AB  - AIM(S): The aim of this study was to explore the challenges of providing
      continuity within the 24-hour nursing service. It explored why nurses work at
      night and what issues this raises for them. BACKGROUND: The manner in which new
      ways of working affect the work or CPD (Continuing Professional Development)
      requirements of ward-based nurses or their community counterparts has received
      little attention. The aim of this study was to explore these issues with a
      diverse sample of practitioners. METHOD(S): Twenty-seven staff from four settings
      (two acute trusts and two community teams) participated in this qualitative study
      employing focus groups and interviews. RESULTS: The nature of night nursing is
      changing; expanded roles and responsibilities are common. However, CPD remains
      problematic, as a result of constraints around time and access. Context-specific
      issues shape the nature of night working in acute and community settings and
      should be considered when planning CPD. CONCLUSION(S): There is a need to re
      examine what CPD is available for practitioners providing care around the clock.
      Traditional forms of CPD may not reflect the evolving reality of practice at
      night. IMPLICATIONS FOR NURSING MANAGEMENT: There is a need to ensure CPD
      opportunities are reviewed regularly to reflect changing 24-hour service demands
      in all settings.

PMID- 19575719
TI  - Provision of continued professional development for non-medical prescribers
      within a South of England Strategic Health Authority: a report on a training
      needs analysis.
AB  - AIMS: This paper reports on a Training Needs Analysis for Non-Medical Prescribers
      commissioned by a south of England Strategic Health Authority. BACKGROUND: The
      aim of the TNA was to inform future policy, educational provision and practice
      development and provide nurse managers with significant information on the
      perceived Continuing Professional Development (CPD) needs of the non-medical
      prescribers. METHODS: Data were collected from a sample of 270 non-medical
      prescribers using an in-depth questionnaire, and telephone interviews with a
      purposive sample of 11 key stakeholders. RESULTS: The findings report: * The
      qualifications that non-medical prescribers possess. * The level of confidence
      described by the non-medical prescribers in their role. * What non-medical
      prescribers identify as their present and future CPD requirements in relation to
      prescribing. * What education and training provision non-medical prescribers have
      attended in relation to their prescribing role since qualifying. CONCLUSIONS: The
      findings suggest, first that short courses that were specific to the non-medical
      prescribers role were considered to be the most popular and useful. However,
      courses needed to be advertised well in advance. Second, training gaps were
      identified. IMPLICATIONS FOR NURSING MANAGEMENT: Pharmacology and prescribing are
      rapidly changing and require regular CPD in order to keep up to date with the
      latest developments. Non-medical prescribing is a comparatively new innovation to
      the NHS, therefore those who are not medically qualified need mentorship from
      experienced prescribers, as well as the encouragement from nurse managers to be
      confident prescribers themselves and enhance patient care.

PMID- 19575720
TI  - Mapping the introduction of assistant practitioner roles in acute NHS (hospital)
      trusts in England.
AB  - AIMS: This mapping study describes current or planned introduction of assistant
      practitioner roles in English National Health Service Acute Hospital Trusts.
      BACKGROUND: In the last decade there has been a growth in nursing support
      workforce numbers and their scope of practice. An important United Kingdom
      support worker development is the Assistant Practitioner role. METHOD: A national
      census was carried out (April 2007) via an emailed questionnaire to Directors of
      Nursing. Quantitative data were analysed using descriptive statistics.
      Qualitative data were analysed using thematic analysis. RESULTS: Eighty-five per
      cent (143/168) of Directors of Nursing, from all 10 English Strategic Health
      Authorities, responded. Forty-six per cent (n = 66) of Trusts had introduced
      assistant practitioners and 22% (n = 31) were planning to implement the role
      before 2009. There is wide variation in assistant practitioner numbers across and
      between Strategic Health Authorities, Trusts and clinical areas. Resistance to
      the role existed in 32% (n = 46) of Trusts. Reasons for resistance included no
      perceived need for the role, lack of evidence of effectiveness, financial
      constraints and professional and patient safety concerns. IMPLICATIONS FOR
      NURSING MANAGEMENT: These findings, which contribute to the international
      evidence-base on health care support workers roles, provide nurse managers with
      numbers of assistant practitioners and their deployment. This is useful for Nurse
      Managers making workforce decisions.

PMID- 19575721
TI  - Health care managers' perspectives on new nursing and midwifery roles: perceived
      impact on patient care and cost effectiveness.
AB  - AIMS: The aim of this study was to explore new nursing and midwifery roles and
      associated levels of practice from the health care providers' perspective. This
      paper will present findings relating to the perceived cost effectiveness of these
      roles and their impact on patient care. BACKGROUND: Profound changes in the way
      the health care systems are organized, managed and financed have resulted in the
      proliferation of new nursing and midwifery roles. However, the evidence base for
      these workforce developments is limited, especially with regard to health care
      providers' perspectives on cost effectiveness and patient outcomes. METHOD:
      Qualitative interviews were carried out with all Directors of Nursing in the 18
      Health and Social Services (HSS) Trusts and the Chief Nurses and Directors of
      Primary Care in the four HSS Boards in Northern Ireland. RESULTS: Key findings
      were as follows: there was widespread support for the development of these roles,
      they are perceived to have a positive impact on patient care; however, the need
      for support was recognized to ensure the continuation of such roles. Securing
      funding was problematic and this was influential on the kind of new roles that
      were developed. IMPLICATIONS FOR NURSING MANAGEMENT: Issues relating to effective
      implementation and the need for further research into the efficacy and effectives
      of such initiatives is required.

PMID- 19575722
TI  - Empowerment, engagement and perceived effectiveness in nursing work environments:
      does experience matter?
AB  - AIMS: We examined the impact of empowering work conditions on nurses' work
      engagement and effectiveness, and compared differences among these relationships
      in new graduates and experienced nurses. BACKGROUND: As many nurses near
      retirement, every effort is needed to retain nurses and to ensure that work
      environments are attractive to new nurses. Experience in the profession and
      generational differences may affect how important work factors interact to affect
      work behaviours. METHODS: We conducted a secondary analysis of survey data from
      two studies and compared the pattern of relationships among study variables in
      two groups: 185 nurses 2 years post-graduation and 294 nurses with more than 2
      years of experience. RESULTS: A multi-group SEM analysis indicated a good fit of
      the hypothesized model. Work engagement significantly mediated the
      empowerment/effectiveness relationship in both groups, although the impact of
      engagement on work effectiveness was significantly stronger for experienced
      nurses. CONCLUSIONS: Engagement is an important mechanism by which empowerment
      affects nurses feelings of effectiveness but less important to new graduates'
      feelings of work effectiveness than empowerment. Implications for nursing
      management Managers must be aware of the role of empowerment in promoting work
      engagement and effectiveness and differential effects on new graduates and more
      seasoned nurses.

PMID- 19575723
TI  - Implementation of Releasing Time to Care - the productive ward.
AB  - BACKGROUND: This paper describes the implementation of the NHS Institute for
      Innovation and Improvement Productive Ward - releasing time to care programme. It
      will discuss the benefits and key successes and provides advice for those wishing
      to implement the programme. In Lord Darzi's Next Stage Review, he advocates an
      ambitious vision of patient centred - clinician led, locally driven NHS. The
      Releasing Time to Care programme is a unique opportunity for everyone working
      within the NHS to improve effectiveness, safety and reliability of the services
      we provide. Whilst being situated within a National Health Service policy
      environment learning from this work can be translated nationally and
      internationally, as the principles underpin the provision of high quality care.
      EVALUATION: Evaluation is currently in relation to each of the 15 modules rather
      than as the programme as a whole. It uses various methods including audit,
      observation, activity follow through, satisfaction surveys and process mapping.
      Each month data is colated for each of the 11 metrics which has shown a reduction
      in falls, drug administration errors and improvement in the recording of patient
      observations. KEY ISSUES: One of the key issues is that an essential component
      for the success of the programme lies in the tangible support of the Trust
      Board/Board of Directors. Evidence shows that this programme improves patient
      satisfaction as it enables the provision of an increase in direct patient care by
      staff and subsequently improved clinical and safety outcomes. Ward Sister/Charge
      Nurse development includes Leadership, Project management and Lean Methodology
      techniques. CONCLUSION: The Releasing Time to Care programme is a key component
      of the Next Stage Review. It will create productive organisations by being a
      catalyst for the transformation of Trust services, enabling staff to spend more
      time caring for patients and users. This release in time will result in better
      outcomes and subsequent improvement with patient and staff satisfaction and
      experience of the NHS as well as a cultural change for the workforce.
      IMPLICATIONS FOR NURSING MANAGEMENT: Releasing Time to Care, also known as the
      productive ward, offers a systematic way of delivering safe, high quality care to
      patients across healthcare settings. The Institute for Innovation and
      Improvement, have devised a programme of 15 modules based on 'lean' methodology.
      It has been widely piloted and in January 2008 was rolled out as a national
      initiative with 50 million pound pump priming money. Evidence shows that the
      programme can improve patient satisfaction as it enables the provision of an
      increase in direct patient care by staff and subsequent improved clinical and
      safety outcomes. The programme has to be implemented in a structured manner in
      order to assure its success and release the benefits. Core to this success is
      Board level commitment. Board members need to sign up to and understand the
      concepts of the programme and their role in supporting the ward staff. The
      organisation needs to understand the benefits that the programme will bring to
      the organisation as well as the challenges. The Board needs to understand that
      the programme is focussed on improving the quality of care for patients and not
      an opportunity to reduce costs.

PMID- 19575725
TI  - Eruptive melanocytic naevi following melanotan injection.

PMID- 19575724
TI  - Practical aspects of lifestyle modifications and behavioural interventions in the
      treatment of overactive bladder and urgency urinary incontinence.
AB  - Behavioural interventions are effective treatments for overactive bladder (OAB)
      and urgency urinary incontinence (UUI). They are in part aimed at improving
      symptoms with patient education on healthy bladder habits and lifestyle
      modifications, including the establishment of normal voiding intervals,
      elimination of bladder irritants from the diet, management of fluid intake,
      weight control, management of bowel regularity and smoking cessation. Behavioural
      interventions also include specific training techniques aimed at re-establishing
      normal voiding intervals and continence. Training techniques include bladder
      training, which includes a progressive voiding schedule together with relaxation
      and distraction for urgency suppression, and multicomponent behavioural training,
      which, in conjunction with pelvic floor muscle (PFM) exercises, includes PFM
      contraction to control urgency and increase the interval between voids.
      Guidelines for the conservative treatment of OAB and UUI have been published by
      several organisations and the physiological basis and evidence for the
      effectiveness of behavioural interventions, including lifestyle modifications, in
      the treatment of OAB and UUI have been described. However, many primary care
      clinicians may have a limited awareness of the evidence supporting the often
      straight-forward treatment recommendations and guidance for incorporating
      behavioural interventions into busy primary care practices, because most of this
      information has appeared in the specialty literature. The purpose of this review
      is to provide an overview of behavioural interventions for OAB and UUI that can
      be incorporated with minimal time and effort into the treatment armamentarium of
      all clinicians that care for patients with bladder problems. Practical supporting
      materials that will facilitate the use of these interventions in the clinic are
      included; these can be used to help patients understand lifestyle choices and
      voiding behaviours that may improve function in patients experiencing OAB
      symptoms and/or UUI as well as promote healthy bladder behaviours and perhaps
      even prevent future bladder problems. Interventions for stress urinary
      incontinence are beyond the scope of this review.

PMID- 19575726
TI  - Psoriasis and streptococci: postscript regarding extra domain A fibronectin.

PMID- 19575727
TI  - Metastatic basal cell carcinoma: report of two cases treated with cetuximab.

PMID- 19575728
TI  - The cause of acantholysis in pemphigus: further support for the 'basal cell
      shrinkage' hypothesis.

PMID- 19575729
TI  - Quantification of wound oedema after dermatological surgery.
AB  - BACKGROUND: Postoperative wound oedema causing increased suture tension is
      thought to be a possible cause of scars known as suture marks. Quantification of
      such oedema has not previously been reported in the literature. Measures to
      accommodate wound oedema may include the adoption of alternative suture
      techniques and the use of more elastic suture materials. OBJECTIVES: To quantify
      wound expansion after skin surgery and to identify any contributory factors, and
      to determine the ability of eight commonly used skin suture materials to stretch
      under increasing tension. METHODS: Forty consecutive adult patients attending a
      dermatology department for routine skin surgery in December 2002 were recruited.
      Details including body site, nature of the lesion excised and dimensions of the
      open wound were recorded. The distance between entry and exit points of an untied
      suture at the time of skin surgery was measured and then repeated 24 h
      postoperatively. The ability of eight different suture materials to stretch when
      an increasing force was applied was measured by hanging standard weights from the
      sutures and measuring the suture length for each force applied. RESULTS: Thirty
      nine patients completed the study. All wounds expanded postoperatively, with a
      mean lateral expansion of 1.0 mm. There was a strong association between the
      width of the unsutured wound after excision and the subsequent wound expansion.
      Commonly used sutures in skin surgery were found to be relatively inelastic at
      forces under 0.2 kg. The monofilament Novofil (Davis & Geck, Danbury, CT, U.S.A.)
      exhibited the greatest degree of stretch of those tested. CONCLUSIONS: There is
      considerable oedema in the first 24 h after skin surgery, particularly with wider
      excisions. This needs to be considered when choosing suturing materials and
      techniques to avoid excessive suture tension.

PMID- 19575730
TI  - Observational cross-sectional study comparing Breslow thickness of melanoma
      arising from naevi and melanoma de novo.

PMID- 19575731
TI  - Confocal laser scanning microscopy in micrographic surgery (three-dimensional
      histology) of basal cell carcinomas.

PMID- 19575732
TI  - Immunohistochemical expression of cyclin-dependent kinase-2 in psoriasis.

PMID- 19575733
TI  - Mondor's disease.
AB  - Mondor's disease (MD) is a rare condition, which is considered a thrombophlebitis
      of the subcutaneous veins. It commonly occurs on the anterolateral
      thoracoabdominal wall, but it can also occur on the penis, groin, antecubital
      fossa and posterior cervical region. The clinical features are a sudden and
      typically asymptomatic onset of a cord-like induration, although some patients
      report a feeling of 'strain'. It is a self-limiting process that lasts a short
      period of time, which may be the reason why there are few reports about its
      diagnosis and treatment. Its pathogenesis has remained unclear, because of the
      lack of methods to reliably differentiate between veins and lymphatic vessels.
      Immunohistochemical staining for CD31 and D240 has been identified recently as
      the best method to distinguish small veins from lymphatic vessels, making it a
      valuable technique in diagnosing not only MD, but also many other diseases in
      which veins or lymphatic vessels are affected. MD has been associated with
      several systemic diseases such as breast cancer and hypercoagulability states,
      thus laboratory studies are recommended to exclude any possible systemic
      disorders. As this condition is usually a benign and self-limiting process,
      vigorous treatment is only recommended when the process is symptomatic or
      recurrent.

PMID- 19575734
TI  - Skin care for preterm and term neonates.
AB  - Neonatal skin experiences a progressive adaptation to the extrauterine
      environment during which special care is needed. The immaturity of the epidermal
      barrier in the neonatal period may cause dry skin, vulnerability to trauma, rapid
      onset of microbial colonization and percutaneous drug toxicity. This article
      reviews the practical implications for hygiene, bathing practices, skin
      integrity, emollient use, infection control and exposure to percutaneous toxic
      agents in preterm and term infants.

PMID- 19575735
TI  - Chromoblastomycosis: clinical presentation and management.
AB  - Chromoblastomycosis is an important subcutaneous mycotic infection that is
      endemic worldwide but more common in the tropics. It is caused by the traumatic
      inoculation of the skin with pigmented saprophytic moulds, and the principal
      infective species are Fonsecaea pedrosoi and Cladophialophora carrionii. Although
      chromoblastomycosis is not known to be fatal, it is characteristically chronic,
      and can be complicated by lymphatic damage and neoplastic transformation. It is
      one of the more difficult-to-treat mycoses, and a variety of antifungal regimens
      often combined with various physical treatments can be used.

PMID- 19575736
TI  - The survival effect of E-cadherin and catenins in colorectal carcinomas.
AB  - AIM: The E-cadherin/catenin complex plays an important role in epithelial tissue
      architecture. Decreased expression of cell adhesion molecules (E-cadherin, alpha
      , beta- and gamma-catenin) have been reported to correlate with invasive
      behaviour. The aim of this study was to investigate the relation between the
      expression of adhesion molecules and clinicopathological characteristics and
      survival in colorectal carcinoma. METHOD: The expression of adhesion molecules
      were studied by immunohistochemistry in 138 colorectal carcinomas. RESULTS: The
      mean age of the patients was 65 years (range: 21-89 years). In primary
      carcinomas, a reduction in membranous expression of E-cadherin, alpha-catenin,
      beta-catenin, gamma-catenin was demonstrated (70%, 68%, 73%, 77%, respectively).
      Nuclear expression of beta-catenin was found in eight (5%) patients. Decreased
      membranous beta- and gamma-catenin expression significantly correlated with
      tumour differentiation (P = 0.013, P = 0.03, respectively). There was a
      significant association between advanced stage of the tumour and decreased
      membranous alpha-catenin expression (P = 0.012). Decreased E-cadherin and beta
      catenin membranous expression correlated with short survival following curative
      resection of the primary tumour (P = 0.04, P = 0.03, respectively). CONCLUSION:
      The decreased membranous expression of E-cadherin and beta-catenin and increased
      cytoplasmic expression of beta-catenin might be used as a prognostic marker to
      monitor patients with colorectal cancer.

PMID- 19575737
TI  - Laparoscopic excision of rectovaginal endometriosis: report of a prospective
      study and review of the literature.
AB  - AIM: The surgical management of rectovaginal endometriosis is challenging. We
      present our experience of the laparoscopic management of these difficult cases,
      together with a review of the current literature. METHOD: A prospective database
      was established for all patients undergoing surgery for Deep Infiltrating
      Endometriosis (DIE) with rectovaginal and/or ureteric and bladder nodules.
      Outcomes analysed include operation performed, conversion and complication rates,
      and length of stay. These outcomes were compared with other laparoscopic rectal
      resections for alternative diagnoses recorded in the database and with outcomes
      seen in a literature review of studies on the surgical management of
      endometriosis. RESULTS: Between April 2004 and November 2007, 54 patients
      underwent laparoscopic excision of rectovaginal endometriosis by a combined
      colorectal and gynaecological surgical team. Out of the 54 patients, 37% of
      patients underwent a rectal wall shave, 13% had a disc excision of the rectal
      wall, and 50% underwent segmental resection. There was a conversion rate of 4%,
      median duration of stay was 3 days, with 2% requiring transfusion. Major
      complications occurred in 7% of patients, with 4% requiring reoperation. Patients
      undergoing segmental resection for endometriosis had a higher complication rate
      than those having surgery for other diagnoses. There was an increased incidence
      of anastomotic stenosis, with histopathological results suggesting that the
      disease process might have contributed to this occurrence. CONCLUSIONS:
      Laparoscopic resection of rectovaginal endometriosis may be associated with a
      higher incidence of complications than resections performed for other diagnoses.

PMID- 19575738
TI  - There is no increased risk for colorectal cancer and adenomas in patients with
      diverticulitis: a retrospective longitudinal study.
AB  - AIM: This study was designed to assess the relationship between diverticulitis
      and the development of colorectal cancer (CRC) and colonic adenomas. METHOD: A
      retrospective study was longitudinally conducted. Patients who had been admitted
      to the hospital between 1990 and 2000 with diverticulitis were retrieved and the
      incidence of CRC and prevalence of colonic adenomas in these patients was
      determined. Data were collected from the electronic clinical and pathology
      records. The incidence of CRC and prevalence of adenomas in this patient cohort
      was compared with the general population. The patients were followed until 2008.
      RESULTS: A total of 288 patients with diverticulitis were included (167 of whom
      were female patients [58%]). The mean age of patients at admittance for
      diverticulitis was 66 years (range: 27-92). CRC was detected in five patients
      (1.7%) (95% CI 0.8-3.5) with a mean age of 77 years; colonic adenomas were found
      in 18 patients (6.3%) (95% CI 4.3-9.0) with a mean age of 62 years. The lifetime
      risks of developing CRC and adenomas were presumed to be 4% and 20% respectively.
      Expected rates for CRC and adenomas in our patients were calculated as 17 (95% CI
      4.0-8.6) and 69 patients (95% CI 20.1-28.3) respectively. CONCLUSION: This study
      showed a lower prevalence of CRC and colonic adenomas in patients with
      diverticulitis compared with the lifetime risk which means that diverticulitis is
      not a risk factor for development of CRC and adenomas. Long-term colonic
      screening after a negative colonoscopy for diverticulitis (generally performed
      several weeks after recovery) does not seem to be justified.

PMID- 19575739
TI  - Autologous platelet-derived growth factors (platelet-rich plasma) as an adjunct
      to mucosal advancement flap in high cryptoglandular perianal fistulae: a pilot
      study.
AB  - AIM: The aim of this study was to explore autologous platelet-rich plasma as an
      adjunct to the staged mucosal advancement flap in the treatment of perianal
      fistulae. METHOD: Between February 2006 and May 2007, 10 patients with fistula
      tracts transversing from the middle-third or upper part of the anal sphincter
      were treated for at least 3 months with noncutting setons prior to definitive
      closure by autologous platelet-rich plasma as an adjunct to a mucosal advancement
      flap. Five patients smoked tobacco. RESULTS: The study group consisted of six
      women and four men with a median age of 44 (range 30-75) years and a median
      follow up of 26 (range 17-32) months. One (10%) patient had a recurrent fistula.
      No new continence disorders developed after definitive treatment in both groups.
      CONCLUSION: Platelet-rich plasma as an adjunct to a staged mucosal advancement
      flap for the treatment of perianal cryptoglandular fistulae is a promising
      treatment modality and seems to establish a high healing rate.

PMID- 19575741
TI  - Patient satisfaction with lower gastrointestinal endoscopy: doctors, nurse and
      nonmedical endoscopists.
AB  - AIM: Assessment of patient satisfaction with lower gastrointestinal endoscopy
      (LGE) comprising colonoscopy and flexible sigmoidoscopy is gaining increasing
      importance. We have now trained non healthcare professionals such as nonmedical
      endoscopists (NMEs) to perform LGE to overcome shortage of trained endoscopists.
      The aim of this study was to prospectively determine patient satisfaction,
      factors affecting satisfaction with LGE and to compare with nurses, NME and
      medical endoscopists, in terms of patient satisfaction. METHOD: Consecutive
      patients undergoing LGE answered specially developed patient satisfaction
      questionnaire at discharge and 24 h thereafter. This questionnaire was a
      modification of m-Group Health Association of America questionnaire. Construct
      and face validity of questionnaire were tested by an expert group. Demographic
      and clinical data was prospectively collected. Multivariate regression analysis
      was performed to determine factors influencing patient satisfaction. RESULTS:
      Some 503 patients were surveyed after LGE. Examinations were performed by nurse
      (n = 105), doctor (n = 191), or NMEs (n = 155). There were no differences between
      three groups in terms of completion rates/complications. No differences were
      detected between endoscopists in patient rating for overall satisfaction (P =
      0.6), technical skills (P = 0.58), communication skills (P = 0.61) or
      interpersonal skills (0.59). Multivariate regression analysis showed that higher
      preprocedure anxiety, history of pelvic operations/hysterectomy and higher pain
      scores were associated with adverse patient satisfaction and preprocedure
      anxiety, history of hysterectomy and female gender were associated with higher
      pain scores. CONCLUSION: This study has shown that there are no differences in
      patient satisfaction with LGE performed by nurse, doctor or NME. The most
      important factor affecting patient satisfaction is degree of discomfort/pain
      experienced by patient.

PMID- 19575740
TI  - A randomized, double-blind, placebo-controlled trial of polyethylene glycol
      effects on fasting and postprandial rectal sensitivity and symptoms in
      hypersensitive constipation-predominant irritable bowel syndrome.
AB  - AIM: To assess the effect of polyethylene glycol 3350 (PEG) on fasting and
      postprandial (PP) perception of rectal distension and symptoms in hypersensitive
      constipation-predominant irritable bowel syndrome (IBS-C). METHODS: Forty-two
      patients meeting Rome II criteria for IBS-C and with a pain threshold of < 32
      mmHg were included in a randomized, double-blind, placebo-controlled trial.
      Patients received either oral PEG, 3.45 g t.i.d. orally for 30 days or placebo.
      Rectal sensitivity was assessed before and after treatment with a barostat using
      the ascending method of limits, during basal and PP periods. RESULTS: No changes
      in fasting and PP rectal tone and thresholds for first sensation, gas sensation,
      urge to defecate, and pain was observed with PEG in relation to placebo. In both
      groups, pressure at which patients crossed the thresholds for noxious (PEG: from
      28 +/- 8.8 to 22 +/- 6.9 mmHg) and non noxious (PEG: from 16 +/- 4.9 to 12 +/-
      3.6 mmHg) stimuli decreased compared with pretreatment values. PEG improved
      consistency of faeces and showed a trend to diminish blood in faeces. PEG and
      placebo increased bowel movements per week (P < 0.001), and relieved symptoms
      without significant side-effects. CONCLUSIONS: Both PEG 3350 and placebo were
      clinically useful in patients with IBS-C, an effect that cannot be explained by
      changes in rectal tone and sensation. The results support the concept that
      visceral sensitivity is not stable and has a heterogeneous response to drugs, and
      suggest the existence of a post healing hypersensitivity state.

PMID- 19575742
TI  - Randomized controlled trial of patient-controlled sedation for colonoscopy:
      Entonox vs modified patient-maintained target-controlled propofol.
AB  - AIM: Propofol sedation is often associated with deep sedation and decreased
      manoeuvrability. Patient-maintained sedation has been used in such patients with
      minimal side-effects. We aimed to compare novel modified patient-maintained
      target-controlled infusion (TCI) of propofol with patient-controlled Entonox
      inhalation for colonoscopy in terms of analgesic efficacy (primary outcome),
      depth of sedation, manoeuvrability and patient and endoscopist satisfaction
      (secondary outcomes). METHOD: One hundred patients undergoing elective
      colonoscopy were randomized to receive either TCI propofol or Entonox. Patients
      in the propofol group were administered propofol initially to achieve a target
      concentration of 1.2 MUg/ml and then allowed to self-administer a bolus of
      propofol (200 MUg/kg/ml) using a patient-controlled analgesia pump with a
      handset. Entonox group patients inhaled the gas through a mouthpiece until caecum
      was reached and then as required. Sedation was initially given by an anaesthetist
      to achieve a score of 4 (Modified Observer's Assessment of Alertness and Sedation
      Scale), and colonoscopy was then started. Patients completed an anxiety score
      (Hospital Anxiety and Depression questionnaire), a baseline letter cancellation
      test and a pain score on a 100-mm visual analogue scale before and after the
      procedure. All patients completed a satisfaction survey at discharge and 24 h
      postprocedure. RESULTS: The median dose of propofol was 174 mg, and the median
      number of propofol boluses was four. There was no difference between the two
      groups in terms of pain recorded (95% confidence interval of the difference 
      0.809, 5.02) and patient/endoscopist satisfaction. There was no difference
      between the two groups in either depth of sedation or manoeuvrability.
      CONCLUSION: Both Entonox and the modified TCI propofol provide equally effective
      sedation and pain relief, simultaneously allowing patients to be easily
      manoeuvred during the procedures.

PMID- 19575743
TI  - The assessment of lymph nodes missed in mesenteric tissue after standard
      dissection of colorectal cancer specimens.
AB  - OBJECTIVE: We studied fresh mesenteric and mesorectal tissue after standard
      dissection of colorectal cancer specimens using a clearing method to evaluate
      lymph nodes (LN) that could have been missed. METHOD: After traditional
      dissection, 50 consecutive unfixed residual mesenteric and mesorectal tissues
      were entirely managed by a new clearing solution, which incorporates hydrochloric
      acid obtaining a really good degree of fat dissolution, facilitating the
      identification of missed LNs. RESULTS: By fat clearance, 498 (mean per specimen,
      10) additional LNs were found, most of them (83%) varying in size from 1 to 5 mm.
      and 22 (4.41%) LNs revealed tumour metastases. In two rectal carcinoma specimens
      that had been treated by neoadjuvant chemoradiotherapy, no LNs were found by
      traditional dissection; after checking by the clearing method, additional LNs
      were harvested in both. Three patients were reclassified and upstaged.
      CONCLUSION: According to our findings, after standard dissection in the remaining
      mesentery of colorectal specimen there are missed positive LNs, which should be
      evaluated to avoid pathological understaging.

PMID- 19575744
TI  - Earlier diagnosis and treatment of symptomatic bowel cancer: can it be achieved
      and how much will it improve survival?
AB  - AIM: To determine current delays in diagnosis and treatment of bowel cancer, when
      and why they occur, and what effect they have on survival. METHOD: A detailed
      review of the literature based on the development of the GP referral guidelines
      in 2000. RESULTS: There is no evidence of a reduction in the delay to diagnosis
      and treatment of bowel cancer over the last 60 years. There is no strong
      theoretical basis for a benefit from earlier diagnosis of symptomatic bowel
      cancer and this is consistent with observational studies. CONCLUSION: Campaigns
      to earlier diagnose bowel cancer will not be successful unless new strategies are
      developed. There is substantial evidence that earlier diagnosis of symptomatic
      bowel cancer will not improve survival in the majority of patients. However as
      excessive delays still occur in some patients it is reasonable to continue to aim
      to diagnose and treat all bowel cancer within 6 months of the onset of symptoms
      with an overall median of 3-4 months.

PMID- 19575745
TI  - TB or not TB: a disease forgotten, but not gone.

PMID- 19575746
TI  - Co-Infection of cattle with Fasciola hepatica and Mycobacterium bovis-
      immunological consequences.
AB  - Fasciola hepatica, the liver fluke, is a common parasite of cattle in much of the
      world. Previously, we have shown that cattle infected with F. hepatica have
      altered responsiveness (delayed type hypersensitivity reaction and cytokine
      responses) to M. bovis BCG infection. We hypothesized that co-infection with F.
      hepatica would, likewise, alter the immune response of cattle to virulent M.
      bovis infection, with possible implications for disease diagnosis and disease
      progression. Our previous work with F. hepatica/M. bovis BCG-infected cattle
      demonstrated a reduction in interferon (IFN)-gamma responsiveness in co-infected
      animals. Similar findings are reported here with virulent M. bovis following
      aerosol infection. The epidemiological significance of these findings, also,
      require exploration, particularly in view of the considerable resources devoted
      to the diagnosis and eradication of bovine tuberculosis, and the high prevalence
      of F. hepatica infection in areas where eradication has proved difficult.

PMID- 19575747
TI  - A 'pilot' study on air-travel and venous thromboembolism.

PMID- 19575748
TI  - Antitumor effects of 2-oxoglutarate through inhibition of angiogenesis in a
      murine tumor model.
AB  - Hypoxia-inducible factor 1 (HIF-1) plays essential roles in tumor angiogenesis
      and growth by regulating the transcription of several key genes in response to
      hypoxic stress and growth factors. HIF-1 is a heterodimeric transcriptional
      activator consisting of inducible alpha and constitutive beta subunits. In
      oxygenated cells, proteins containing the prolyl hydroxylase domain (PHD)
      directly sense intracellular oxygen concentrations. PHDs tag HIF-1alpha subunits
      for polyubiquitination and proteasomal degradation by prolyl hydroxylation using
      2-oxoglutarate (2-OX) and dioxygen. Our recent studies showed that 2-OX reduces
      HIF-1alpha, erythropoietin, and vascular endothelial growth factor (VEGF)
      expression in the hepatoma cell line Hep3B when under hypoxic conditions in
      vitro. Here, we report that similar results were obtained in Lewis lung cancer
      (LLC) cells in in vitro studies. Furthermore, 2-OX showed potent antitumor
      effects in a mouse dorsal air sac assay and a murine tumor xenograft model. In
      the dorsal air sac assay, 2-OX reduced the numbers of newly formed vessels
      induced by LLC cells. In a murine tumor xenograft model, intraperitoneal
      injection of 2-OX significantly inhibited tumor growth and angiogenesis in tumor
      tissues. Moreover, 5-fluorouracil combined with 2-OX significantly inhibited
      tumor growth in this model, which was accompanied by reduction of Vegf gene
      expression and inhibited angiogenesis in tumor tissues. These results suggest
      that 2-OX is a promising anti-angiogenic therapeutic agent.

PMID- 19575749
TI  - Effect of the alcoholic extract of Ashwagandha leaves and its components on
      proliferation, migration, and differentiation of glioblastoma cells:
      combinational approach for enhanced differentiation.
AB  - Ashwagandha (Withania somnifera) is widely used in the Indian traditional system
      of medicine, Ayurveda. Although it is claimed to have a large variety of health
      promoting effects, including therapeutic effects on stress and disease, the
      mechanisms of action have not yet been determined. In the present study, we aimed
      to investigate the growth inhibition and differentiation potential of the
      alcoholic extract of Ashwagandha leaves (i-Extract), its different constituents
      (Withaferin A, Withanone, Withanolide A) and their combinations on glioma (C6 and
      YKG1) cell lines. Withaferin A, Withanone, Withanolide A and i-Extract markedly
      inhibited the proliferation of glioma cells in a dose-dependent manner and
      changed their morphology toward the astrocytic type. Molecular analysis revealed
      that the i-Extract and some of its components caused enhanced expression of glial
      fibrillary acidic protein, change in the immunostaining pattern of mortalin from
      perinuclear to pancytoplasmic, delay in cell migration, and increased expression
      of neuronal cell adhesion molecules. The data suggest that the i-Extract and its
      components have the potential to induce senescence-like growth arrest and
      differentiation in glioma cells. These assays led us to formulate a unique
      combination formula of i-Extract components that caused enhanced differentiation
      of glial cells.

PMID- 19575750
TI  - Estrogen signaling pathway and its imaging in human breast cancer.
AB  - Recent remarkable progress in hormonal therapy has provided great benefit to
      breast cancer patients, but it also evokes novel issues: how accurately can the
      efficacy of each hormonal therapy be predicted and how can hormonal therapy
      resistant patients be treated? These clinically important issues must be closely
      related to the biological events in each cancer, such as the alteration of
      intracellular multiple estrogen signaling pathways and the estrogen-related
      cancer microenvironment, which has recently revealed by molecular biological
      studies on estrogen and its receptors. However, the estrogen signaling status in
      individual breast cancers has not been clarified yet. Here we present the context
      of these issues and introduce our study of new tools which enable the
      visualization of estrogen signals in individual cancers. The assessment of
      estrogen receptor (ER)-alpha activity in individual cancers or ER-activating
      ability of the cancer microenvironment in each breast cancer patient revealed
      several new findings and interesting observations. We hope that these approaches
      provide new clues about the estrogen-dependent mechanisms of breast cancer
      development, and will be useful to advance the diagnosis and treatment of breast
      cancer patients.

PMID- 19575751
TI  - Improved therapeutic efficacy against murine carcinoma by combining honokiol with
      gene therapy of PNAS-4, a novel pro-apoptotic gene.
AB  - PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA
      damage, can inhibit proliferation via apoptosis when overexpressed in some tumor
      cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit
      angiogenesis, and suppress tumor growth. In the present study, we investigated
      whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced
      by honokiol in vitro, and whether the antiangiogenic activity of honokiol and
      induction of apoptosis by mPNAS-4 could work cooperatively to improve the
      antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine
      colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of
      apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells
      induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in
      vivo systemic administration of an expression plasmid encoding mPNAS-4 and low
      dose honokiol significantly suppressed tumor growth through the enhanced
      induction of apoptosis and the augmented inhibition of angiogenesis. Our data
      suggest that the combined treatment with mPNAS-4 plus honokiol augments antitumor
      effects in vitro and in vivo, and that the improved antitumor activity in vivo
      may be associated with enhanced induction of apoptosis and augmented inhibition
      of angiogenesis. The present study may provide a novel and effective method for
      the treatment of cancer.

PMID- 19575752
TI  - Phase I and pharmacokinetic study of vorinostat (suberoylanilide hydroxamic acid)
      in Japanese patients with solid tumors.
AB  - Vorinostat (suberoylanilide hydroxamic acid), a potent, oral histone deacetylase
      inhibitor, has demonstrated clinical activity in non-Japanese patients with
      various hematological and solid tumors. We sought to determine the maximum
      tolerated dose and a recommended phase II dose for 18 Japanese patients with
      solid tumors (median age, 58 years; range, 25-72 years) who failed standard
      therapy. Patients received vorinostat for 14 days followed by a 7-day rest. The
      initial dose was 100 mg twice daily escalating by 100 mg twice daily. Once-daily
      dosing was tested at 400 and 500 mg. A maximum tolerated dose could not be
      identified. Dose-limiting toxicities (thrombocytopenia, anorexia, and fatigue)
      were observed in two of six patients receiving 200 mg twice daily and in one of
      six patients receiving 500 mg once daily. In the 100-500 mg dose range,
      vorinostat area under the concentration-time curve increased in proportion to
      dose with a pharmacokinetic profile similar to that established in non-Japanese
      patients. Vorinostat doses of 200 mg twice daily or 500 mg once daily for 14 days
      followed by a 7-day rest were well tolerated and are candidate doses for phase II
      trials, although a maximum tolerated dose for vorinostat was not reached.

PMID- 19575753
TI  - Symmetrical pigmented sclerosis enclosed by pruritic erythema: a new variant of
      morphoea?

PMID- 19575754
TI  - Endothelial cell apoptosis in severe drug-induced bullous eruptions.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)
      are characterized by extensive keratinocyte apoptosis mediated by cytotoxic
      proteins. Similar features have been found in another severe dysimmune syndrome,
      allogeneic acute graft-versus-host disease, where endothelial cell apoptosis has
      been recently characterized. OBJECTIVES: To determine whether endothelial cell
      apoptosis occurs in dermal vessels of TEN and SJS, and whether it is linked to
      expression of cytotoxic proteins. METHODS: Skin biopsies of eight patients with
      severe drug-induced bullous eruptions (four TEN, four SJS), eight with drug
      induced urticaria and eight healthy controls were compared. Blood vessel damage
      was studied by electron microscopy and quantified by CD31 immunostaining.
      Apoptotic cells, characterized by electron microscopy, were quantified on
      terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick
      end labelling assay. Immunohistochemistry was also used to characterize and
      quantify inflammatory cells and granzyme B, tumour necrosis factor (TNF)-alpha
      and Fas ligand (FasL) expression. RESULTS: Endothelial cell apoptosis was
      observed in all TEN and SJS cases: it occurred in 85% of the vessel sections. It
      occurred in one case of drug-induced urticaria, in 5% of vessel sections, but not
      in healthy controls. Numbers of CD68+ macrophages and CD8+ T lymphocytes were
      significantly higher in TEN and SJS compared with both other groups; granzyme B
      and TNF-alpha but not FasL were expressed. CONCLUSIONS: Characterization of
      endothelial cell apoptosis in TEN and SJS is important to assess a factor
      worsening skin damage, with possible extension to other organs. It may also be
      useful for the development of novel therapeutic strategies.

PMID- 19575755
TI  - Staphylococcus aureus and hand eczema severity.
AB  - BACKGROUND: The role of bacterial infections in hand eczema (HE) remains to be
      assessed. OBJECTIVES: To determine the prevalence of Staphylococcus aureus in
      patients with HE compared with controls, and to relate presence of S. aureus,
      subtypes and toxin production to severity of HE. METHODS: Bacterial swabs were
      taken at three different visits from the hand and nose in 50 patients with HE and
      50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to
      clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus
      strains. The Hand Eczema Severity Index was used for severity assessment.
      RESULTS: Staphylococcus aureus was found on the hands in 24 patients with HE and
      four controls (P < 0.001), and presence of S. aureus was found to be related to
      increased severity of the eczema (P < 0.001). Patients carried identical S.
      aureus types on the hands and in the nose in all cases, and between visits in 90%
      of cases. Ten different CC types were identified, no association with severity
      was found, and toxin-producing strains were not found more frequently in patients
      with HE than in controls. CONCLUSIONS: Staphylococcus aureus was present on hands
      in almost half of all patients with HE, and was significantly related to severity
      of the disease. This association indicates that S. aureus could be an important
      cofactor for persistence of HE.

PMID- 19575756
TI  - Audit of incomplete excision rates of basal cell carcinoma: analysis of 1972
      cases from four U.K. regions.

PMID- 19575757
TI  - Topical treatment of perianal eczema with tacrolimus 0.1%.
AB  - BACKGROUND: Perianal eczema is an inflammatory skin disease with a high
      prevalence in most industrialized countries. As general practitioners and
      dermatologists frequently see patients with perianal eczema the need for
      efficient, fast and safe therapies is high. Topical calcineurin inhibitors such
      as tacrolimus (FK506) ameliorate cutaneous inflammation and associated pruritus
      in an array of inflammatory dermatoses. OBJECTIVES: To investigate the effect of
      topical tacrolimus in perianal eczema. METHODS: Twenty-four patients with
      perianal eczema were treated with tacrolimus 0.1% ointment twice daily on the
      affected skin area for 2 weeks. RESULTS: All returning patients showed clinical
      improvement as assessed by macroscopic appearance and clinical score (modified
      SCORAD index). CONCLUSIONS: In this short-term trial we demonstrate that topical
      tacrolimus 0.1% is safe, efficient and well tolerated in patients with perianal
      eczema irrespective of the underlying cause.

PMID- 19575759
TI  - Optimizing warfarin reversal--an ex vivo study.
AB  - BACKGROUND: Warfarin reversal is a common clinical situation. This is commonly
      performed using vitamin K and, depending on the urgency, fresh frozen plasma
      (FFP), prothrombin complex concentrates (PCCs), or activated factor VII. Even
      though PCCs are widely used, the ideal dosing regimen is far from established.
      OBJECTIVES: To verify differences in warfarin reversal patterns using FFP,
      recombinant FVIIa (rFVIIa), and PCC; and to test the hypothesis that
      supratherapeutic International Normalized Ratios (INRs) might not correlate with
      thrombin generation (TG) and identify the ideal concentrations of PCC required to
      reverse various INR thresholds. METHODS: We studied the effects of FFP, rFVIIa
      and Beriplex P/N on the INR and TG, using the calibrated automated thrombography
      assay in ex vivo warfarinized plasma. Plasmas with different INRs were spiked
      with different concentrations of Beriplex P/N. RESULTS: Beriplex P/N was the only
      agent that completely normalized TG and the INR. The endogenous thrombin
      potential (ETP) and the peak thrombin showed a significant negative correlation
      with all INRs. The ETP and velocity of TG reached a plateau at an INR of
      approximately 4.0. A concentration equivalent to a dose of 30 IU kg(-1) Beriplex
      P/N normalized the ETP, the INR, FII, FVII, FIX and FX of samples with INRs > or
      = 4.0. Higher doses resulted in hypercoagulable TG patterns. A concentration
      equivalent to a dose of 20 IU kg(-1) was sufficient to reverse warfarin at an INR
      range of 2.0-3.9, as judged by the same tests. CONCLUSIONS: Warfarin reversal
      algorithms could be simplified with the adoption of this strategy utilizing two
      doses of PCC, depending on the INR of the patient. This would also lead to cost
      reductions and, possibly, a reduction in thrombotic risk.

PMID- 19575760
TI  - IL-10 inhibits apoptosis and microvesiculation of human monocytes.

PMID- 19575758
TI  - Metagenomics reveals diversity and abundance of meta-cleavage pathways in
      microbial communities from soil highly contaminated with jet fuel under air
      sparging bioremediation.
AB  - The extradiol dioxygenase diversity of a site highly contaminated with aliphatic
      and aromatic hydrocarbons under air-sparging treatment was assessed by functional
      screening of a fosmid library in Escherichia coli with catechol as substrate. The
      235 positive clones from inserts of DNA extracted from contaminated soil were
      equivalent to one extradiol dioxygenase-encoding gene per 3.6 Mb of DNA screened,
      indicating a strong selection for genes encoding this function. Three subfamilies
      were identified as being predominant, with 72, 55 and 43 fosmid inserts carrying
      genes, related to those encoding TbuE of Ralstonia pickettii PK01 (EXDO-D), IpbC
      of Pseudomonas sp. JR1 (EXDO-K2) or DbtC of Burkholderia sp. DBT1 (EXDO-Dbt),
      respectively, whereas genes encoding enzymes related to XylE of Pseudomonas
      putida mt-2 were not observed. Genes encoding oxygenases related to
      isopropylbenzene dioxygenases were usually colocalized with genes encoding EXDO
      K2 dioxygenases. Functional analysis of representative proteins indicated a
      subcluster of EXDO-D proteins to show exceptional high affinity towards different
      catecholic substrates. Based on V(max)/K(m) specificity constants, a task-sharing
      between different extradiol dioxygenases in the community of the contaminated
      site can be supposed, attaining a complementary and community-balanced catalytic
      power against diverse catecholic derivatives, as necessary for effective
      degradation of mixtures of aromatics.

PMID- 19575762
TI  - Prospective assessment of the effect on quality of life of anti-tumour necrosis
      factor therapy for perineal Crohn's fistulas.
AB  - BACKGROUND: Anti-tumour necrosis factor (TNF) therapy effectively treats Crohn's
      perineal fistulas (CPF); the effect on health-related quality of life (HRQoL)
      remains unknown. AIMS: To evaluate the effect of anti-TNF therapy on the HRQoL of
      patients with CPF in daily clinical practice. METHODS: Prospective evaluation of
      clinical and magnetic resonance imaging (MRI) responses, disease activity
      (Perianal Disease Activity Index - PDAI), and HRQoL assessment [Inflammatory
      Bowel Disease Questionnaire (IBDQ)] in patients receiving anti-TNF therapy for
      CPF treated up to 12 months. RESULTS: In all, 26 patients with CPF were treated
      (mean age 39 years; 19 infliximab, 7 adalimumab). At baseline, 85% patients had
      impaired IBDQ scores (mean 137; 'normal' >170). At 12 months, mean increases in
      IBDQ score for infliximab and adalimumab treated patients were 40 and 41 points
      respectively (P < 0.05). There were significant improvements in all IBDQ
      subscores (bowel, emotional, systemic, social) at 12 months (all P < or = 0.003).
      Fourteen patients (74%) on infliximab and six on adalimumab (86%) achieved IBDQ
      score > or =170. Mean increase in IBDQ score was 50, 34 and 16 points in patients
      with clinical fistula closure (P < 0.001), clinical response (P = 0.002) and no
      response (n = 1) respectively. IBDQ score increased for patients with MRI healing
      (P < 0.001) and MRI improvement (P = 0.016), but not for those with no MRI change
      (n = 2). IBDQ correlated significantly with PDAI at baseline and at 12 months.
      CONCLUSION: Anti-TNF therapy improves HRQoL in patients with CPF at 12 months and
      this improvement is most pronounced in patients with clinical and MRI healing.

PMID- 19575763
TI  - Systematic review: accuracy of symptom-based criteria for diagnosis of irritable
      bowel syndrome in primary care.
AB  - BACKGROUND: Despite the trend towards making a positive diagnosis of irritable
      bowel syndrome (IBS), many health care providers approach IBS as a diagnosis of
      exclusion. AIM: To summarize available evidence on the diagnostic performance of
      symptom-based IBS criteria in excluding organic diseases, and of individual signs
      and symptoms in diagnosing IBS and to additionally assess the influence of
      sources of heterogeneity on diagnostic performance. METHODS: We searched PubMed
      and EMBASE and screened references. Studies were selected if the design was a
      primary diagnostic study; the patients were adults consulting because of non
      acute abdominal symptoms; the diagnostic test included an externally validated
      set of IBS criteria, signs, or symptoms. Data extraction and quality assessment
      were performed by two reviewers independently. The review adhered to the most
      recent guidelines as described in the Cochrane Diagnostic Reviewers' Handbook.
      RESULTS: A total of 25 primary diagnostic studies were included in the review.
      The performance of symptom-based criteria in the exclusion of organic disease was
      highly variable. Patients fulfilling IBS criteria had, however, a lower risk of
      organic diseases than those not fulfilling the criteria. CONCLUSIONS: With none
      of the criteria showing sufficiently homogeneous and favourable results, organic
      disease cannot be accurately excluded by symptom-based IBS criteria alone.
      However, the low pre-test probability of organic disease especially among
      patients who meet symptom-based criteria in primary care argues against
      exhaustive diagnostic evaluation. We advise validation of the new Rome III
      criteria in primary care populations.

PMID- 19575764
TI  - Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most
      prescribed drugs worldwide and have now probably overtaken Helicobacter pylori as
      the most common cause of gastrointestinal injury in Western countries. Further
      understanding of the pathogenesis of NSAID-induced ulcers is important to enable
      the development of novel and effective preventive strategies. AIMS: To provide an
      update on recent advances in our understanding of the cellular and molecular
      mechanisms involved in the development of NSAID-induced ulcers. METHODS: A
      Medline search was performed to identify relevant literature using search terms
      including 'nonsteroidal anti-inflammatory drugs, aspirin, gastric ulcer, duodenal
      ulcer, pathogenesis, pharmacogenetics'. RESULTS: The mechanisms of NSAID-induced
      ulcers can be divided into topical and systemic effects and the latter may be
      prostaglandin-dependent (through COX inhibition) or prostaglandin-independent.
      Genetic factors may play an important role in determining individual
      predisposition. CONCLUSIONS: The pathogenesis of NSAID-induced peptic ulcers is
      complex and multifactorial. Recent advances in cellular and molecular biology
      have highlighted the importance of various prostaglandin-independent mechanisms.
      Pharmacogenetic studies may provide further insights into the pathogenetic
      mechanisms of NSAID-induced ulcers and help identify patients at increased risk.

PMID- 19575766
TI  - Hypothyroidism in neonates post-iodinated contrast media: a systematic review.
AB  - AIM: To determine if neonates exposed to iodinated contrast media are at risk of
      hypothyroidism. METHODS: A systematic review was conducted by searching
      electronic databases (e.g. MEDLINE), contacting experts and scanning reference
      lists. Studies examining the effects of contrast media on neonatal thyroid
      function were included. Two reviewers independently screened the literature and
      assessed the risk of bias, while one reviewer abstracted data. RESULTS: Eleven
      studies were included; nine studies directly examined the risk of hypothyroidism
      (n = 182 neonates exposed to contrast media). All were highly affected by bias.
      In the three studies including term infants, one showed a trend towards increased
      thyroid-stimulating hormone (TSH) and decreased free thyroxine (FT4) among
      exposed groups. Six of 72 (8.3%) term infants exposed were treated for
      hypothyroidism. In studies of premature infants, there was a trend towards
      increased TSH (n = 3/7 studies), lower total thyroxine (n = 1), decreased
      triidothyronine and FT4 (n = 3) and hypothyroidism (n = 5). Twenty of 110 (18.2%)
      premature infants exposed were treated for hypothyroidism. CONCLUSION:
      Hospitalized neonates exposed to iodinated contrast media are at risk for
      abnormal thyroid function and development of hypothyroidism. Premature infants
      might be at increased risk. Well-controlled studies are required to replicate our
      findings because the included studies were highly affected by bias.

PMID- 19575767
TI  - Single-centre vs. population-based outcome data of extremely preterm infants at
      the limits of viability.
AB  - AIM: In response to the disappointing outcome data of the population-based
      EPICure study published in 2000, we compared the outcome of infants 22 0/7 to 25
      6/7 weeks of gestational age (GA) in a single tertiary care centre 2000-2004 with
      that of EPICure. METHODS: EPICure tools and definitions, including 30 months'
      Bayley Scales. RESULTS: Of 83 infants <26 weeks born alive, more were admitted to
      intensive care--82% vs. 68% (p < 0.0001)--and more infants survived to discharge
      (57% vs. 26%, p < 0.0001; 69% vs. 39%, p < 0.01, of those admitted to intensive
      care). More infants, as a percentage of live births, survived without severe
      (41%, 34/83 vs. 20%, 233/1185, p < 0.0001) or overall disability (22%, 18/83 vs.
      13%, 155/1185, p = 0.03). However, at the border of viability--GA 23 and 24 weeks
      -the rate of infants surviving without overall disability was not significantly
      higher (13%, 6/45 vs. 9%, 56/623). CONCLUSION: In infants <26 weeks of GA,
      increased rates of survival and survival without disability were observed in a
      single-centre inborn cohort born 5-8 years later than the EPICure cohort. This
      did not translate into increased survival without overall disability in infants
      of 23-24 weeks of GA.

PMID- 19575769
TI  - What's in a name?

PMID- 19575771
TI  - 2009 update on phosphodiesterase type 5 inhibitor therapy part 1: Recent studies
      on routine dosing for penile rehabilitation, lower urinary tract symptoms, and
      other indications (CME).
AB  - INTRODUCTION: Highly selective inhibitors of phosphodiesterase type 5 (PDE5I)
      have been commercially available for over a decade. Our knowledge of these drugs
      continues to expand. AIMS: To review developments within the past 18 months on
      the utilization of PDE5I in preclinical studies and clinical practice. The focus
      of this article is on updates on regular dosing regimens of PDE5I other than the
      newly approved daily dose tadalafil. METHODS: PubMed search utilizing the terms
      "phosphodiesterase type 5 inhibitor," PDE5 inhibitor,""sildenafil,""vardenafil,"
      and "tadalafil." Articles were screened based on whether or not they addressed
      issues of routine dosing of PDE5I. Manuscripts on the newly approved daily dose
      tadalafil for erectile dysfunction (ED) were deferred for analysis in a separate
      manuscript in this series. MAIN OUTCOME MEASURES: Peer reviewed publications on
      routine dosing of PDE5I published in the medical literature since 2007. RESULTS:
      There have been numerous publications in the past 2 years regarding routine
      dosing of PDE5I for three major urological indications; penile rehabilitation,
      stuttering priapism, and management of lower urinary tract symptoms (LUTS).
      Evidence from basic science investigations has indicated that daily dose PDE5I
      may improve erectile function and exert a number of beneficial tissue effects on
      the penis. Unfortunately, data from human series of routine dose PDE5I for penile
      rehabilitation after radical prostatectomy are conflicting, with the two largest
      studies showing no benefit to daily dose therapy in the post-radical
      prostatectomy and the general ED populations. PDE5I are generally helpful at
      reducing symptoms of LUTS, particularly when given in conjunction with alpha
      blockers. Routine dosing of PDE5I has also been utilized successfully for
      management of stuttering ischemic priapism and several other medical indications.
      CONCLUSIONS: PDE5I given as routine doses have clinical promise. Further research
      is required to clarify their safety and efficacy for various indications.

PMID- 19575773
TI  - Intralesional injection therapy for Peyronie's disease.

PMID- 19575768
TI  - Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans
      SKN-1/Nrf.
AB  - Studies in model organisms have identified regulatory processes that profoundly
      influence aging, many of which modulate resistance against environmental or
      metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1
      is important for oxidative stress resistance and acts in multiple longevity
      pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2
      detoxification genes in response to stress. Phase 2 enzymes defend against oxygen
      radicals and conjugate electrophiles that are produced by Phase 1 detoxification
      enzymes, which metabolize lipophilic compounds. Here, we have used expression
      profiling to identify genes and processes that are regulated by SKN-1 under
      normal and stress-response conditions. Under nonstressed conditions SKN-1
      upregulates numerous genes involved in detoxification, cellular repair, and other
      functions, and downregulates a set of genes that reduce stress resistance and
      lifespan. Many of these genes appear to be direct SKN-1 targets, based upon
      presence of predicted SKN-binding sites in their promoters. The metalloid sodium
      arsenite induces skn-1-dependent activation of certain detoxification gene
      groups, including some that were not SKN-1-upregulated under normal conditions.
      An organic peroxide also triggers induction of a discrete Phase 2 gene set, but
      additionally stimulates a broad SKN-1-independent response. We conclude that
      under normal conditions SKN-1 has a wide range of functions in detoxification and
      other processes, including modulating mechanisms that reduce lifespan. In
      response to stress, SKN-1 and other regulators tailor transcription programs to
      meet the challenge at hand. Our findings reveal striking complexity in SKN-1
      functions and the regulation of systemic detoxification defenses.

PMID- 19575775
TI  - Use and abuse of Rigiscan in the diagnosis of erectile dysfunction.
AB  - INTRODUCTION: Nocturnal penile tumescence and rigidity (NPTR, or, more simply,
      NPT) studies, with or without the help of a recording computer (Rigiscan), have
      been traditionally positioned at the head of several erectile dysfunction (ED)
      diagnostic flowcharts with the aim to distinguish between psychogenic and organic
      etiology. Shall we continue to consider these tools as a diagnostic gold standard
      in ED diagnosis? METHODS: Four scientists with expertise and/or interest in the
      area of ED pathophysiology and diagnosis were asked to contribute their opinions.
      MAIN OUTCOME MEASURE: To give to The Journal of Sexual Medicine's reader new
      stimuli to reexamine a still largely utilized tool utilized in sexual medicine's
      clinical practice. RESULTS: Of the four experts discussing the topic, the first
      who is the section editor of the Controversy section, believes that NPT/Rigiscan
      cannot be considered a useful diagnostic tool for differential diagnosis in ED.
      He is supported by the physiological considerations of the second expert and by
      the experimental evidence produced and discussed by the expert number four who
      questions the accuracy, reliability, and usefulness of these tools to measure a
      critical aspect of the erection physiology which is the adequate rigidity. In
      contrast, with several good arguments, the third expert still suggests the use of
      these tools, perhaps not for every man presenting with ED, but at least for the
      patient with no neurovascular risk factors who presents with a history suggestive
      of a psychogenic cause. CONCLUSION: The reader will judge if the expensive,
      complicated, and time-consuming effort to record nocturnal erectile activity is
      or is not useful anymore for the patient and for orienting the treatment choices.

PMID- 19575776
TI  - Are clinicians being prepared to care for abused women? A survey of health
      professional education in Ontario, Canada.
AB  - BACKGROUND: The current project undertook a province-wide survey and
      environmental scan of educational opportunities available to future health care
      providers on the topic of intimate partner violence (IPV) against women. METHODS:
      A team of experts identified university and college programs in Ontario, Canada
      as potential providers of IPV education to students in health care professions at
      the undergraduate and post-graduate levels. A telephone survey with contacts
      representing these programs was conducted between October 2005 and March 2006.
      The survey asked whether IPV-specific education was provided to learners, and if
      so, how and by whom. RESULTS: In total, 222 eligible programs in dentistry,
      medicine, nursing and other allied health professions were surveyed, and 95%
      (212/222) of programs responded. Of these, 57% reported offering some form of IPV
      specific education, with undergraduate nursing (83%) and allied health (82%)
      programs having the highest rates. Fewer than half of undergraduate medical (43%)
      and dentistry (46%) programs offered IPV content. Postgraduate programs ranged
      from no IPV content provision (dentistry) to 41% offering content (nursing).
      CONCLUSION: Significant variability exists across program areas regarding the
      methods for IPV education, its delivery and evaluation. The results of this
      project highlight that expectations for an active and consistent response by
      health care professionals to women experiencing the effects of violence may not
      match the realities of professional preparation.

PMID- 19575777
TI  - Development of a nursing intervention to facilitate optimal antiretroviral
      treatment taking among people living with HIV.
AB  - BACKGROUND: Failure by a large portion of PLHIV to take optimally ARV treatment
      can have serious repercussions on their health. The absence of a systematic
      treatment-taking promotion program in Quebec prompted stakeholders to develop
      jointly a theory- and evidence-based nursing intervention to this end. This
      article describes the results of a collective effort by researchers, clinicians
      and PLHIV to share their knowledge and create an appropriate intervention.
      METHODS: Intervention mapping was used as the framework for developing the
      intervention. First, the target population and environmental conditions were
      analyzed and a literature review conducted to identify predictors of optimal
      treatment taking. The predictors to emerge were self-efficacy and attitudes.
      Performance objectives were subsequently defined and crossed-referenced with the
      predictors to develop a matrix of change objectives. Then, theories of self
      efficacy and persuasion (the predictors to emerge from step 1), together with
      practical strategies derived from these theories, were used to design the
      intervention. Finally, the sequence and content of the intervention activities
      were defined and organized, and the documentary material designed. RESULTS: The
      intervention involves an intensive, personalized follow-up over four direct
      contact sessions, each lasting 45-75 minutes. Individuals are engaged in a
      learning process that leads to the development of skills to motivate themselves
      to follow the therapeutic plan properly, to overcome situations that make taking
      the antiretroviral medication difficult, to cope with side-effects, to relate to
      people in their social circle, and to deal with health professionals. CONCLUSION:
      The intervention was validated by various health professionals and pre-tested
      with four PLHIV. Preliminary results support the suitability and viability of the
      intervention. A randomized trial is currently underway to verify the
      effectiveness of the intervention in promoting optimal antiretroviral treatment
      taking.

PMID- 19575778
TI  - Regulation of DNA replication by the S-phase DNA damage checkpoint.
AB  - Cells slow replication in response to DNA damage. This slowing was the first DNA
      damage checkpoint response discovered and its study led to the discovery of the
      central checkpoint kinase, Ataxia Telangiectasia Mutated (ATM). Nonetheless, the
      manner by which the S-phase DNA damage checkpoint slows replication is still
      unclear. The checkpoint could slow bulk replication by inhibiting replication
      origin firing or slowing replication fork progression, and both mechanisms appear
      to be used. However, assays in various systems using different DNA damaging
      agents have produced conflicting results as to the relative importance of the two
      mechanisms. Furthermore, although progress has been made in elucidating the
      mechanism of origin regulation in vertebrates, the mechanism by which forks are
      slowed remains unknown. We review both past and present efforts towards
      determining how cells slow replication in response to damage and try to resolve
      apparent conflicts and discrepancies within the field. We propose that inhibition
      of origin firing is a global checkpoint mechanism that reduces overall DNA
      synthesis whenever the checkpoint is activated, whereas slowing of fork
      progression reflects a local checkpoint mechanism that only affects replisomes as
      they encounter DNA damage and therefore only affects overall replication rates in
      cases of high lesion density.

PMID- 19575779
TI  - Cerebrovascular mental stress reactivity is impaired in hypertension.
AB  - BACKGROUND: Brachial artery reactivity in response to shear stress is altered in
      subjects with hypertension. Since endothelial dysfunction is generalized, we
      hypothesized that carotid artery (CA) reactivity would also be altered in
      hypertension. PURPOSE: To compare (CA endothelium-dependent vasodilation in
      response to mental stress in normal and hypertensive subjects. METHODS: We
      evaluated CA reactivity to mental stress in 10 young healthy human volunteers
      (aged 23 +/- 4 years), 20 older healthy volunteers (aged 49 +/- 11 years) and in
      28 patients with essential hypertension (aged 51 +/- 13 years). In 10 healthy
      volunteers and 12 hypertensive subjects, middle cerebral artery (MCA) PW
      transcranial Doppler was performed before and 3 minutes after mental stress.
      RESULTS: Mental stress by Stroop color word conflict, math or anger recall tests
      caused CA vasodilation in young healthy subjects (0.61 +/- 0.06 to 0.65 +/- 0.07
      cm, p < 0.05) and in older healthy subjects (0.63 +/- 0.06 to 0.66 +/- 0.07 cm, p
      < 0.05), whereas no CA vasodilation occurred in hypertensive subjects (0.69 +/-
      0.06 to 0.68 +/- 0.07 cm; p, NS). CA blood flow in response to mental stress
      increased in young healthy subjects (419 +/- 134 to 541 +/- 209 ml, p < 0.01 vs.
      baseline) and in older healthy subjects (351 +/- 114 to 454 +/- 136 ml, p < 0.01
      vs. baseline) whereas no change in blood flow (444 +/- 143 vs. 458 +/- 195 ml; p,
      0.59) occurred in hypertensive subjects. There was no difference in the CA
      response to nitroglycerin in healthy and hypertensive subjects. Mental stress
      caused a significant increase in baseline to peak MCA systolic (84 +/- 22 to 95
      +/- 22 cm/s, p < 0.05), diastolic (42 +/- 12 to 49 +/- 14 cm/s, p < 0.05) as well
      as mean (30 +/- 13 to 39 +/- 13 cm/s, p < 0.05) PW Doppler velocities in normal
      subjects, whereas no change in systolic (70 +/- 18 to 73 +/- 22 cm/s, p < 0.05),
      diastolic (34 +/- 14 to 37 +/- 14 cm/s, p = ns) or mean velocities (25 +/- 9 to
      26 +/- 9 cm/s, p = ns) occurred in hypertensive subjects, despite a similar
      increase in heart rate and blood pressure in response to mental stress in both
      groups. CONCLUSION: Mental stress produces CA vasodilation and is accompanied by
      an increase in CA and MCA blood flow in healthy subjects. This mental stress
      induced CA vasodilation and flow reserve is attenuated in subjects with
      hypertension and may reflect cerebral vascular endothelial dysfunction.
      Assessment of mental stress induced CA reactivity by ultrasound is a novel method
      for assessing the impact of hypertension on cerebrovascular endothelial function
      and blood flow reserve.

PMID- 19575780
TI  - Survivin counteracts the therapeutic effect of microtubule de-stabilizers by
      stabilizing tubulin polymers.
AB  - BACKGROUND: Survivin is a dual function protein. It inhibits the apoptosis of
      cells by inhibiting caspases, and also promotes cell growth by stabilizing
      microtubules during mitosis. Over-expression of survivin has been demonstrated to
      induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA
      damaging agent) and paclitaxel (microtubule stabilizer) in cancers. However,
      survivin-induced resistance to microtubule de-stabilizers such as Vinca alkaloids
      and Combretastatin A-4 (CA-4)-related compounds were seldom demonstrated in the
      past. Furthermore, the question remains as to whether survivin plays a dominant
      role in processing cytokinesis or inhibiting caspases activity in cells treated
      with anti-mitotic compounds. The purpose of this study is to evaluate the effect
      of survivin on the resistance and susceptibility of human cancer cells to
      microtubule de-stabilizer-induced cell death. RESULTS: BPR0L075 is a CA-4 analog
      that induces microtubule de-polymerization and subsequent caspase-dependent
      apoptosis. To study the relationship between the expression of survivin and the
      resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer
      cell line, KB-L30, was generated for this study. Here, we found that survivin was
      over-expressed in the KB-L30 cells. Down-regulation of survivin by siRNA induced
      hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to
      BPR0L075 in KB-L30 cells. Western blot analysis revealed that down-regulation of
      survivin induced microtubule de-stabilization in both KB and KB-L30 cells.
      However, the same treatment did not enhance the down-stream caspase-3/-7
      activities in BPR0L075-treated KB cells. Translocation of a caspase-independent
      apoptosis-related molecule, apoptosis-inducing factor (AIF), from cytoplasm to
      the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment.
      CONCLUSION: In this study, survivin plays an important role in the stability of
      microtubules, but not with caspases inhibition. Over-expression of survivin
      counteracts the therapeutic effect of microtubule de-stabilizer BPR0L075 probably
      by stabilizing tubulin polymers, instead of the inhibition of caspase activity in
      cancer cells. Besides microtubule-related caspase-dependent cell death, caspase
      independent mitotic cell death could be initiated in survivin/BPR0L075
      combination treatments. We suggest that combining microtubule de-stabilizers with
      a survivin inhibitor may attribute to a better clinical outcome than the use of
      anti-mitotic monotherapy in clinical situations.

PMID- 19575781
TI  - Use of a T cell interferon gamma release assay in the investigation for suspected
      active tuberculosis in a low prevalence area.
AB  - BACKGROUND: In settings with low background prevalence of tuberculosis (TB)
      infection, interferon-gamma release assays (IGRA) could be useful for diagnosing
      active TB. This study aims to evaluate the performance of QuantiFERON-TB Gold
      (QFT-G) in the investigation for suspected active TB, with particular attention
      to patients originating in high-incidence countries. Furthermore, factors
      associated with QFT-G results in patients with active TB were assessed. METHODS:
      From patients investigated for clinically suspected active TB, blood was obtained
      for QFT-G testing, in addition to routine investigations. Positive (PPV) and
      negative (NPV) predictive values for QFT-G were calculated, comparing patients
      with confirmed TB and those with other final diagnoses. QFT-G results in TB
      patients originating from countries with intermediate or high TB incidence were
      compared with QFT-G results from a control group of recently arrived asymptomatic
      immigrants from high-incidence countries. Factors associated with QFT-G outcome
      in patients with confirmed TB were assessed. RESULTS: Among 141 patients, 41/70
      (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%)
      patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of
      67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%,
      respectively, and 90.5% and 66.7% for subjects with extrapulmonary
      manifestations. Comparing patients from high-incidence countries with controls
      yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed
      TB and positive QFT-G results were characterized by a lower median peripheral
      white blood cell count (5.9 x 10(9)/L vs. 8.8 x 10(9)/L; P < 0.001) and a higher
      median body mass index (22.7 vs. 20.7; P = 0.043) as compared to QFT-G-negative
      TB patients. CONCLUSION: The overall PPV and NPV of QFT-G for identifying active
      TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of
      QFT-G for this purpose is questionable. However, a high PPV was observed for
      extrapulmonary TB and QFT-G might be considered in the diagnostic process in this
      situation. The PPV and NPV for identifying active TB among persons originating
      from regions with high-and intermediate TB incidence was similar to that observed
      in subjects originating in the low-incidence region.

PMID- 19575782
TI  - Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle
      cells.
AB  - muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B
      (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2)
      mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC
      contraction and proliferation. This study was designed to investigate the ETA and
      ETB receptor intracellular signaling in human VSMCs and used phosphorylation
      (activation) of ERK1/2 as a functional signal molecule for endothelin receptor
      activity. RESULTS: Subconfluent human VSMCs were stimulated by ET-1 at different
      concentrations (1 nM-1 microM). The activation of ERK1/2 was examined by
      immunofluorescence, Western blot and phosphoELISA using specific antibody against
      phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent
      activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline
      level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished
      by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1
      inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETA
      antagonist BQ123 blocked the ET-1 effect, while the ETB antagonist BQ788 had no
      significant effect. However, a selective ETB receptor agonist, Sarafotoxin 6c
      (S6c) caused a time-dependent ERK1/2 activation with a maximal effect by less
      than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan
      concentration up to 10 microM further inhibited ET-1-induced activation of ERK1/2
      and had a stronger inhibitory effect than BQ123 or the combined use of BQ123 and
      BQ788. To further explore ET-1 intracellular signaling, PKC inhibitors
      (staurosporin and GF109203X), PKC-delta inhibitor (rottlerin), PKA inhibitor (H
      89), and phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) were
      applied. The inhibitors showed significant inhibitory effects on ET-1-induced
      activation of ERK1/2. However, blockage of L-type Ca2+ channels or
      calcium/calmodulin-dependent protein kinase II, chelating extracellular Ca2+ or
      emptying internal Ca2+ stores, did not affect ET-1-induced activation of ERK1/2.
      CONCLUSION: The ETA receptors predominate in the ET-1-induced activation of
      ERK1/2 in human VSMCs, which associates with increments in intracellular PKC, PKA
      and PI3K activities, but not Ca2+ signalling.

PMID- 19575783
TI  - The effect of HER2 expression on cisplatin-based chemotherapy in advanced non
      small cell lung cancer patients.
AB  - INTRODUCTION: The prognostic value of HER2 expression in patients with advanced
      non-small cell lung cancer remains controversial. The relationship between HER2
      expression, and platinum resistance and patient survival, was investigated.
      METHODS: Seventy-three consecutive patients (median age, 61 years) with stage
      IIIB and IV non-small cell lung cancer, admitted between February 2004 and
      December 2006, were included in this study. Sixty-one patients received
      gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given
      as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two
      25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1.
      Both treatment paradigms were repeated on a 21-day cycle. Tumor response was
      evaluated by comparing tumor size on computerized tomography scans before and
      after three cycles of chemotherapy. HER2 status was examined by
      immunohistochemical analysis of paraffin-embedded specimens. RESULTS: HER2 was
      positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity,
      13 (61.9%) responded to chemotherapy with either a complete response, partial
      remission, or evidence of stable disease. Of 52 HER2-negative patients, 48
      (92.3%) exhibited a response to chemotherapy. The difference in response to
      therapy between HER2-positive and -negative patients was statistically
      significant (p = 0.003). The median overall survival duration for all patients
      was 13 months. Median overall survival time was 14 months for HER2-negative
      patients and 10 months for HER2-positive patients (log-rank p = 0.007).
      CONCLUSION: Non-small cell lung cancer patients with high expression of HER2
      exhibited resistance to cisplatin-based chemotherapies that are the standard
      treatment for this disease. Our results indicate that HER2 status may be a
      predictive and prognostic factor for cisplatin- based therapy response and
      disease survival.

PMID- 19575784
TI  - Characteristics and natural course of vertebral endplate signal (Modic) changes
      in the Danish general population.
AB  - BACKGROUND: Vertebral endplate signal changes (VESC) are more common among
      patients with low back pain (LBP) and/or sciatica than in people who are not
      seeking care for back pain. The distribution and characteristics of VESC have
      been described in people from clinical and non-clinical populations. However,
      while the clinical course of VESC has been studied in patients, the natural
      course in the general population has not been reported. The objectives of this
      prospective observational study were to describe: 1) the distribution and
      characteristics of VESC in the lumbar spine, 2) its association with disc
      degeneration, and 3) its natural course from 40 to 44 years of age. METHODS:
      Three-hundred-and-forty-four individuals (161 men and 183 women) sampled from the
      Danish general population had MRI at the age of 40 and again at the age of 44.
      The following MRI findings were evaluated using standardised evaluation
      protocols: type, location, and size of VESC, disc signal, and disc height.
      Characteristics and distribution of VESC were analysed by frequency tables. The
      association between VESC and disc degeneration was analysed by logistic
      regression analysis. The change in type and size of VESC was analysed by cross
      tabulations of variables obtained at age 40 and 44 and tested using McNemar's
      test of symmetry. RESULTS: Two-thirds (67%) of VESC found in this study were
      located in the lower part of the spine (L4-S1). VESC located at disc levels L1-L3
      were generally small and located only in the anterior part of the vertebra,
      whereas those located at disc levels L4-S1 were more likely to extend further
      into the vertebra and along the endplate. Moreover, the more the VESC extended
      into the vertebra, the more likely it was that the adjacent disc was degenerated.
      The prevalence of endplate levels with VESC increased significantly from 6% to 9%
      from age 40 to 44. Again, VESC that was only observed in the endplate was more
      likely to come and go over the four-year period compared with those which
      extended further into the vertebra, where it generally persisted. CONCLUSION: The
      prevalence of VESC increased significantly over the four-year period.
      Furthermore, the results from this study indicate that the distribution of VESC,
      its association with disc degeneration and its natural course, is dependent on
      the size of the signal changes.

PMID- 19575785
TI  - Dynamics of different-sized solid-state nanocrystals as tracers for a drug
      delivery system in the interstitium of a human tumor xenograft.
AB  - INTRODUCTION: Recent anticancer drugs have been made larger to pass selectively
      through tumor vessels and stay in the interstitium. Understanding drug movement
      in association with its size at the single-molecule level and estimating the time
      needed to reach the targeted organ is indispensable for optimizing drug delivery
      because single cell-targeted therapy is the ongoing paradigm. This report
      describes the tracking of single solid nanoparticles in tumor xenografts and the
      estimation of arrival time. METHODS: Different-sized nanoparticles measuring 20,
      40, and 100 nm were injected into the tail vein of the female Balb/c nu/nu mice
      bearing human breast cancer on their backs. The movements of the nanoparticles
      were visualized through the dorsal skin-fold chamber with the high-speed confocal
      microscopy that we manufactured. RESULTS: An analysis of the particle
      trajectories revealed diffusion to be inversely related to the particle size and
      position in the tumor, whereas the velocity of the directed movement was related
      to the position. The difference in the velocity was the greatest for 40-nm
      particles in the perivascular to the intercellular region: difference = 5.8 nm/s.
      The arrival time of individual nanoparticles at tumor cells was simulated. The
      estimated times for the 20-, 40-, and 100-nm particles to reach the tumor cells
      were 158.0, 218.5, and 389.4 minutes, respectively, after extravasation.
      CONCLUSIONS: This result suggests that the particle size can be individually
      designed for each goal. These data and methods are also important for
      understanding drug pharmacokinetics. Although this method may be subject to
      interference by surface molecules attached on the particles, it has the potential
      to elucidate the pharmacokinetics involved in constructing novel drug-delivery
      systems involving cell-targeted therapy.

PMID- 19575786
TI  - How can accelerated development of bioenergy contribute to the future UK energy
      mix? Insights from a MARKAL modelling exercise.
AB  - BACKGROUND: This work explores the potential contribution of bioenergy
      technologies to 60% and 80% carbon reductions in the UK energy system by 2050, by
      outlining the potential for accelerated technological development of bioenergy
      chains. The investigation was based on insights from MARKAL modelling, detailed
      literature reviews and expert consultations. Due to the number and complexity of
      bioenergy pathways and technologies in the model, three chains and two
      underpinning technologies were selected for detailed investigation: (1)
      lignocellulosic hydrolysis for the production of bioethanol, (2) gasification
      technologies for heat and power, (3) fast pyrolysis of biomass for bio-oil
      production, (4) biotechnological advances for second generation bioenergy crops,
      and (5) the development of agro-machinery for growing and harvesting bioenergy
      crops. Detailed literature searches and expert consultations (looking inter alia
      at research and development needs and economic projections) led to the
      development of an 'accelerated' dataset of modelling parameters for each of the
      selected bioenergy pathways, which were included in five different scenario runs
      with UK-MARKAL (MED). The results of the 'accelerated runs' were compared with a
      low-carbon (LC-Core) scenario, which assesses the cheapest way to decarbonise the
      energy sector. RESULTS: Bioenergy was deployed in larger quantities in the
      bioenergy accelerated technological development scenario compared with the LC
      Core scenario. In the electricity sector, solid biomass was highly utilised for
      energy crop gasification, displacing some deployment of wind power, and nuclear
      and marine to a lesser extent. Solid biomass was also deployed for heat in the
      residential sector from 2040 in much higher quantities in the bioenergy
      accelerated technological development scenario compared with LC-Core. Although
      lignocellulosic ethanol increased, overall ethanol decreased in the transport
      sector in the bioenergy accelerated technological development scenario due to a
      reduction in ethanol produced from wheat. CONCLUSION: There is much potential for
      future deployment of bioenergy technologies to decarbonise the energy sector.
      However, future deployment is dependent on many different factors including
      investment and efforts towards research and development needs, carbon reduction
      targets and the ability to compete with other low carbon technologies as they
      become deployed. All bioenergy technologies should become increasingly more
      economically competitive with fossil-based technologies as feedstock costs and
      flexibility are reduced in line with technological advances.

PMID- 19575788
TI  - Evaluation of the performance of tests for spatial randomness on prostate cancer
      data.
AB  - BACKGROUND: Spatial global clustering tests can be used to evaluate the
      geographical distribution of health outcomes. The power of several of these tests
      has been evaluated and compared using simulated data, but their performance using
      real unadjusted data and data adjusted for individual- and area-level covariates
      has not been reported previously.We evaluated data on prostate cancer histologic
      tumor grade and stage of disease at diagnosis for incident cases of prostate
      cancer reported to the Maryland Cancer Registry during 1992-1997. We analyzed
      unadjusted data as well as expected counts from models that were adjusted for
      individual-level covariates (race, age and year of diagnosis) and area-level
      covariates (census block group median household income and a county-level
      socioeconomic index). We chose 3 spatial clustering tests that are commonly used
      to evaluate the geographic distribution of disease: Cuzick-Edwards' k-NN (k
      Nearest Neighbors) test, Moran's I and Tango's MEET (Maximized Excess Events
      Test). RESULTS: For both grade and stage at diagnosis, we found that Cuzick
      Edwards' k-NN and Moran's I were very sensitive to the percent of population
      parameter selected. For stage at diagnosis, all three tests showed that the
      models with individual- and area-level adjustments reduced clustering the most,
      but did not reduce it entirely. CONCLUSION: Based on this specific example,
      results suggest that these tests provide useful tools for evaluating spatial
      clustering of disease characteristics, both before and after consideration of
      covariates.

PMID- 19575787
TI  - Differential expression proteomics to investigate responses and resistance to
      Orobanche crenata in Medicago truncatula.
AB  - BACKGROUND: Parasitic angiosperm Orobanche crenata infection represents a major
      constraint for the cultivation of legumes worldwide. The level of protection
      achieved to date is either incomplete or ephemeral. Hence, an efficient control
      of the parasite requires a better understanding of its interaction and associated
      resistance mechanisms at molecular levels. RESULTS: In order to study the plant
      response to this parasitic plant and the molecular basis of the resistance we
      have used a proteomic approach. The root proteome of two accessions of the model
      legume Medicago truncatula displaying differences in their resistance phenotype,
      in control as well as in inoculated plants, over two time points (21 and 25 days
      post infection), has been compared. We report quantitative as well as qualitative
      differences in the 2-DE maps between early- (SA 27774) and late-resistant (SA
      4087) genotypes after Coomassie and silver-staining: 69 differential spots were
      observed between non-inoculated genotypes, and 42 and 25 spots for SA 4087 and SA
      27774 non-inoculated and inoculated plants, respectively. In all, 49 differential
      spots were identified by peptide mass fingerprinting (PMF) following MALDI
      TOF/TOF mass spectrometry. Many of the proteins showing significant differences
      between genotypes and after parasitic infection belong to the functional category
      of defense and stress-related proteins. A number of spots correspond to proteins
      with the same function, and might represent members of a multigenic family or
      post-transcriptional forms of the same protein. CONCLUSION: The results obtained
      suggest the existence of a generic defense mechanism operating during the early
      stages of infection and differing in both genotypes. The faster response to the
      infection observed in the SA 27774 genotype might be due to the action of
      proteins targeted against key elements needed for the parasite's successful
      infection, such as protease inhibitors. Our data are discussed and compared with
      those previously obtained with pea 1 and transcriptomic analysis of other plant
      pathogen and plant-parasitic plant systems.

PMID- 19575789
TI  - Experiences of professional support during pregnancy and childbirth - a
      qualitative study of women with type 1 diabetes.
AB  - BACKGROUND: Women with type 1 diabetes are at high risk of complications during
      both pregnancy and childbirth. Stringent monitoring of blood sugar is required in
      order to improve the chance of giving birth to a healthy child; however, this
      increases the incidence of severe hypoglycaemia. The aim of this study was to
      explore the need for and experience of professional support during pregnancy and
      childbirth among women with type 1 diabetes. METHODS: The study has a lifeworld
      research approach. Six focus groups and four individual interviews were conducted
      with 23 women, 6-24 months after delivery. The participants were encouraged to
      narrate their experiences of pregnancy and childbirth in relation to glycaemic
      control, well-being and provided care. Data analysis was directed towards
      discovering qualitative meanings by identifying and clustering meaning units in
      the text. Further analysis identified eight themes of meaning, classified under
      pregnancy or childbirth, forming a basis for a final whole interpretation of the
      explored phenomenon. RESULTS: The women felt worry about jeopardizing the baby's
      health and this was sometimes made worse by care providers' manner and lack of
      competence and support. The increased attention from care providers during
      pregnancy was experienced as related to the health of the unborn child; not the
      mothers. Women who during pregnancy received care in a disconnected diabetes
      organisation were forced to act as messengers between different care providers.
      CONCLUSION: Clarity in terms of defining responsibilities is necessary during
      pregnancy and childbirth, both among care providers and between the woman and the
      care provider. Furthermore, a decision must be made concerning how to delegate,
      transfer or share diabetes responsibility during labour between the care
      providers and the parents-to-be.

PMID- 19575790
TI  - Are there valid proxy measures of clinical behaviour? A systematic review.
AB  - BACKGROUND: Accurate measures of health professionals' clinical practice are
      critically important to guide health policy decisions, as well as for
      professional self-evaluation and for research-based investigation of clinical
      practice and process of care. It is often not feasible or ethical to measure
      behaviour through direct observation, and rigorous behavioural measures are
      difficult and costly to use. The aim of this review was to identify the current
      evidence relating to the relationships between proxy measures and direct measures
      of clinical behaviour. In particular, the accuracy of medical record review,
      clinician self-reported and patient-reported behaviour was assessed relative to
      directly observed behaviour. METHODS: We searched: PsycINFO; MEDLINE; EMBASE;
      CINAHL; Cochrane Central Register of Controlled Trials; science/social science
      citation index; Current contents (social & behavioural med/clinical med); ISI
      conference proceedings; and Index to Theses. INCLUSION CRITERIA: empirical,
      quantitative studies; and examining clinical behaviours. An independent, direct
      measure of behaviour (by standardised patient, other trained observer or by
      video/audio recording) was considered the 'gold standard' for comparison. Proxy
      measures of behaviour included: retrospective self-report; patient-report; or
      chart-review. All titles, abstracts, and full text articles retrieved by
      electronic searching were screened for inclusion and abstracted independently by
      two reviewers. Disagreements were resolved by discussion with a third reviewer
      where necessary. RESULTS: Fifteen reports originating from 11 studies met the
      inclusion criteria. The method of direct measurement was by standardised patient
      in six reports, trained observer in three reports, and audio/video recording in
      six reports. Multiple proxy measures of behaviour were compared in five of 15
      reports. Only four of 15 reports used appropriate statistical methods to compare
      measures. Some direct measures failed to meet our validity criteria. The accuracy
      of patient report and chart review as proxy measures varied considerably across a
      wide range of clinical actions. The evidence for clinician self-report was
      inconclusive. CONCLUSION: Valid measures of clinical behaviour are of fundamental
      importance to accurately identify gaps in care delivery, improve quality of care,
      and ultimately to improve patient care. However, the evidence base for three
      commonly used proxy measures of clinicians' behaviour is very limited. Further
      research is needed to better establish the methods of development, application,
      and analysis for a range of both direct and proxy measures of behaviour.

PMID- 19575791
TI  - Screening and brief interventions for hazardous alcohol use in accident and
      emergency departments: a randomised controlled trial protocol.
AB  - BACKGROUND: There is a wealth of evidence regarding the detrimental impact of
      excessive alcohol consumption on the physical, psychological and social health of
      the population. There also exists a substantial evidence base for the efficacy of
      brief interventions aimed at reducing alcohol consumption across a range of
      healthcare settings. Primary research conducted in emergency departments has
      reinforced the current evidence regarding the potential effectiveness and cost
      effectiveness. Within this body of evidence there is marked variation in the
      intensity of brief intervention delivered, from very minimal interventions to
      more intensive behavioural or lifestyle counselling approaches. Further the
      majority of primary research has been conducted in single centre and there is
      little evidence of the wider issues of generalisability and implementation of
      brief interventions across emergency departments. METHODS/DESIGN: The study
      design is a prospective pragmatic factorial cluster randomised controlled trial.
      Individual Emergency Departments (ED) (n = 9) are randomised with equal
      probability to a combination of screening tool (M-SASQ vs FAST vs SIPS-PAT) and
      an intervention (Minimal intervention vs Brief advice vs Brief lifestyle
      counselling). The primary hypothesis is that brief lifestyle counselling
      delivered by an Alcohol Health Worker (AHW) is more effective than Brief Advice
      or a minimal intervention delivered by ED staff. Secondary hypotheses address
      whether short screening instruments are more acceptable and as efficient as
      longer screening instruments and the cost-effectiveness of screening and brief
      interventions in ED. Individual participants will be followed up at 6 and 12
      months after consent. The primary outcome measure is performance using a gold
      standard screening test (AUDIT). Secondary outcomes include; quantity and
      frequency of alcohol consumed, alcohol-related problems, motivation to change,
      health related quality of life and service utilisation. DISCUSSION: This paper
      presents a protocol for a large multi-centre pragmatic factorial cluster
      randomised trial to evaluate the effectiveness and cost-effectiveness of
      screening and brief interventions for hazardous alcohol users attending emergency
      departments. TRIAL REGISTRATION: ISRCTN 93681536.

PMID- 19575792
TI  - Does unrestrained single-chamber plethysmography provide a valid assessment of
      airway responsiveness in allergic BALB/c mice?
AB  - BACKGROUND: Unrestrained plethysmography has been used to monitor
      bronchoconstriction because of its ease of use and ability to measure airway
      responsiveness in conscious animals. However, its reliability remains
      controversial. OBJECTIVE: To investigate if unrestrained plethysmography could
      provide a valid interpretation of airway responsiveness in allergic BALB/c mice.
      METHODS: Ovalbumin sensitized BALB/c mice were randomized to receive either a
      single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin
      challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I
      (measured invasively, using lung resistance as the index of responsiveness) and
      OVA-1D-N group (measured non-invasively, using Penh as the index of
      responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D
      N groups based on the above methods. The control groups were sensitized and
      challenged with normal saline. Bronchial alveolar lavage fluid was taken and
      airway histopathology was evaluated for airway inflammation. Nasal responsiveness
      was tested with histamine challenge. RESULTS: Compared with controls, a
      significant increase in airway responsiveness was shown in the OVA-1D-N group (P
      < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed
      higher responsiveness than their controls (P < 0.05). The nasal mucosa was
      infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or
      nasal rubbing in allergic groups appeared more frequent than that in the control
      groups. CONCLUSION: Penh can not be used as a surrogate for airway resistance.
      The invasive measurement is specific to lower airway. Penh measurement (done as a
      screening procedure), must be confirmed by a direct invasive measurement specific
      to lower airway in evaluating lower airway responsiveness.

PMID- 19575793
TI  - Gene expression profiling via LongSAGE in a non-model plant species: a case study
      in seeds of Brassica napus.
AB  - BACKGROUND: Serial analysis of gene expression (LongSAGE) was applied for gene
      expression profiling in seeds of oilseed rape (Brassica napus ssp. napus). The
      usefulness of this technique for detailed expression profiling in a non-model
      organism was demonstrated for the highly complex, neither fully sequenced nor
      annotated genome of B. napus by applying a tag-to-gene matching strategy based on
      Brassica ESTs and the annotated proteome of the closely related model crucifer A.
      thaliana. RESULTS: Transcripts from 3,094 genes were detected at two time-points
      of seed development, 23 days and 35 days after pollination (DAP). Differential
      expression showed a shift from gene expression involved in diverse developmental
      processes including cell proliferation and seed coat formation at 23 DAP to more
      focussed metabolic processes including storage protein accumulation and lipid
      deposition at 35 DAP. The most abundant transcripts at 23 DAP were coding for
      diverse protease inhibitor proteins and proteases, including cysteine proteases
      involved in seed coat formation and a number of lipid transfer proteins involved
      in embryo pattern formation. At 35 DAP, transcripts encoding napin, cruciferin
      and oleosin storage proteins were most abundant. Over both time-points, 18.6% of
      the detected genes were matched by Brassica ESTs identified by LongSAGE tags in
      antisense orientation. This suggests a strong involvement of antisense transcript
      expression in regulatory processes during B. napus seed development. CONCLUSION:
      This study underlines the potential of transcript tagging approaches for gene
      expression profiling in Brassica crop species via EST matching to annotated A.
      thaliana genes. Limits of tag detection for low-abundance transcripts can today
      be overcome by ultra-high throughput sequencing approaches, so that tag-based
      gene expression profiling may soon become the method of choice for global
      expression profiling in non-model species.

PMID- 19575794
TI  - Genomic diversity of pathogenic Escherichia coli of the EHEC 2 clonal complex.
AB  - BACKGROUND: Evolutionary analyses of enterohemorrhagic Escherichia coli (EHEC)
      have identified two distantly related clonal groups: EHEC 1, including serotype
      O157:H7 and its inferred ancestor O55:H7; and EHEC 2, comprised of several
      serogroups (O26, O111, O118, etc.). These two clonal groups differ in their
      virulence and global distribution. Although several fully annotated genomic
      sequences exist for strains of serotype O157:H7, much less is known about the
      genomic composition of EHEC 2. In this study, we analyzed a set of 24 clinical
      EHEC 2 strains representing serotypes O26:H11, O111:H8/H11, O118:H16, O153:H11
      and O15:H11 from humans and animals by comparative genomic hybridization (CGH) on
      an oligoarray based on the O157:H7 Sakai genome. RESULTS: Backbone genes, defined
      as genes shared by Sakai and K-12, were highly conserved in EHEC 2. The
      proportion of Sakai phage genes in EHEC 2 was substantially greater than that of
      Sakai-specific bacterial (non-phage) genes. This proportion was inverted in
      O55:H7, reiterating that a subset of Sakai bacterial genes is specific to EHEC 1.
      Split decomposition analysis of gene content revealed that O111:H8 was more
      genetically uniform and distinct from other EHEC 2 strains, with respect to the
      Sakai O157:H7 gene distribution. Serotype O26:H11 was the most heterogeneous EHEC
      2 subpopulation, comprised of strains with the highest as well as the lowest
      levels of Sakai gene content conservation. Of the 979 parsimoniously informative
      genes, 15% were found to be compatible and their distribution in EHEC 2 clustered
      O111:H8 and O118:H16 strains by serotype. CGH data suggested divergence of the
      LEE island from the LEE1 to the LEE4 operon, and also between animal and human
      isolates irrespective of serotype. No correlation was found between gene contents
      and geographic locations of EHEC 2 strains. CONCLUSION: The gene content
      variation of phage-related genes in EHEC 2 strains supports the hypothesis that
      extensive modular shuffling of mobile DNA elements has occurred among EHEC
      strains. These results suggest that EHEC 2 is a multiform pathogenic clonal
      complex, characterized by substantial intra-serotype genetic variation. The
      heterogeneous distribution of mobile elements has impacted the diversification of
      O26:H11 more than other EHEC 2 serotypes.

PMID- 19575795
TI  - Ranking candidate genes in rat models of type 2 diabetes.
AB  - BACKGROUND: Rat models are frequently used to find genomic regions that
      contribute to complex diseases, so called quantitative trait loci (QTLs). In
      general, the genomic regions found to be associated with a quantitative trait are
      rather large, covering hundreds of genes. To help selecting appropriate candidate
      genes from QTLs associated with type 2 diabetes models in rat, we have developed
      a web tool called Candidate Gene Capture (CGC), specifically adopted for this
      disorder. METHODS: CGC combines diabetes-related genomic regions in rat with
      rat/human homology data, textual descriptions of gene effects and an array of 789
      keywords. Each keyword is assigned values that reflect its co-occurrence with 24
      different reference terms describing sub-phenotypes of type 2 diabetes (for
      example "insulin resistance"). The genes are then ranked based on the occurrences
      of keywords in the describing texts. RESULTS: CGC includes QTLs from type 2
      diabetes models in rat. When comparing gene rankings from CGC based on one sub
      phenotype, with manual gene ratings for four QTLs, very similar results were
      obtained. In total, 24 different sub-phenotypes are available as reference terms
      in the application and based on differences in gene ranking, they fall into
      separate clusters. CONCLUSION: The very good agreement between the CGC gene
      ranking and the manual rating confirms that CGC is as a reliable tool for
      interpreting textual information. This, together with the possibility to select
      many different sub-phenotypes, makes CGC a versatile tool for finding candidate
      genes. CGC is publicly available at http://ratmap.org/CGC.

PMID- 19575796
TI  - Characterization of subcellular localization of duck enteritis virus UL51
      protein.
AB  - BACKGROUND: Knowledge of the subcellular localization of a protein can provide
      useful insights about its function. While the subcellular localization of many
      alphaherpesvirus UL51 proteins has been well characterized, little is known about
      where duck enteritis virus (DEV) UL51 protein (pUL51) is targeted to. Thus, in
      this study, we investigated the subcellular localization and distribution of DEV
      pUL51 by computer aided analysis, as well as indirect immunofluorescence (IIF)
      and transmission immunoelectron microscopy (TIEM) approaches in DEV-infected
      cells. RESULTS: The DEV UL51 gene product was identified as an approximate 34 kDa
      protein in DEV-infected cells analyzed by western blotting. Computer aided
      analysis suggested that DEV pUL51 is not targeted to the mitochondrial, extra
      cellular or nucleus, but be targeted to the cytoplasmic in host cells, more
      specifically, palmitoylation of the pUL51 through the N-terminal cysteine at
      position 9 makes membrane association and Golgi localization possible. Using IIF
      analysis, we found that DEV pUL51 was first detected in a juxtanuclear region of
      DEV-infected cells at 9 h postinfection (p.i.), and then was detected widely
      distributed in the cytoplasm and especially was stronger in the juxtanuclear
      region from 12 to 60 h p.i. TIEM analysis revealed that DEV pUL51 was mainly
      associated with cytoplasmic virions and also with some membranous structure near
      the pUL51-specific immuno-labeling intracellular virion in the cytoplasmic
      vesicles; moreover, the pUL51 efficiently accumulated in the Golgi apparatus at
      first, and then was sent to the plasma membrane from the Golgi by some unknown
      mechanism. CONCLUSION: In this work, we described the basic characteristics of
      pUL51 subcellular localization and distribution for the first time. From these
      results, we concluded that palmitoylation at the N-terminal cysteine, which is
      conserved in all alphaherpesvirus UL51 homologs, is required for its membrane
      association and Golgi localization, and the pUL51 mainly localized to the
      juxtanuclear region of DEV-infected cells, as well seemed to be incorporated into
      mature virions as a component of the tegument. The research will provide useful
      clues for DEV pUL51 functional analysis, and will be usefull for further
      understanding the localization properties of alphaherpesvirus UL51 homologs.

PMID- 19575797
TI  - A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily
      one day versus artemether/lumefantrine six doses regimen in children and adults
      with uncomplicated falciparum malaria in Cote d'Ivoire.
AB  - BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to
      malaria control. Combination anti-malarial therapy, including artemisinins, has
      been advocated to improve efficacy and limit the spread of resistance. The fixed
      combination of oral artemether-lumefantrine (AL) is highly effective and well
      tolerated. Artemisinin/naphtoquine (AN) is a fixed-dose ACT that has recently
      become available in Africa. The objectives of the study were to compare the
      efficacy and safety of AN and AL for the treatment of uncomplicated falciparum
      malaria in a high transmission-intensity site in Ivory Coast. METHODS: We
      enrolled 122 participants aged 6 months or more with uncomplicated falciparum
      malaria. Participants were randomized to receive either artemisinin/naphtoquine
      or artemether/lumefantrine with variable dose according to their weight. Primary
      endpoints were the risks of treatment failure within 28 days, either unadjusted
      or adjusted by genotyping to distinguish recrudescence from new infection.
      RESULTS: Among 125 participants enrolled, 123 (98.4%) completed follow-up.
      Clinical evaluation of the 123 participants showed that cumulative PCR
      uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4%
      for artemether/lumefantrine. Both artemisinin-based combinations effected rapid
      fever and parasite clearance. INTERPRETATION: These data suggest that Arco could
      prove to be suitable for use as combination antimalarial therapy. Meanwhile,
      pharmacokinetic studies and further efficacy assessment should be conducted
      before its widespread use can be supported.

PMID- 19575798
TI  - Cooperation between NRF-2 and YY-1 transcription factors is essential for
      triggering the expression of the PREPL-C2ORF34 bidirectional gene pair.
AB  - BACKGROUND: Many mammalian genes are organized as bidirectional (head-to-head)
      gene pairs with the two genes separated only by less than 1 kb. The
      transcriptional regulation of these bidirectional gene pairs remains largely
      unclear, but a few studies have suggested that the two closely adjacent genes in
      divergent orientation can be co-regulated by a single transcription factor
      binding to a specific regulatory fragment. Here we report an evolutionarily
      conserved bidirectional gene pair, known as the PREPL-C2ORF34 gene pair, whose
      transcription relies on the synergic cooperation of two transcription factors
      binding to an intergenic bidirectional minimal promoter. RESULTS: While PREPL is
      present primarily in brain and heart, C2ORF34 is ubiquitously and abundantly
      expressed in almost all tissues. Genomic analyses revealed that these two non
      homologous genes are adjacent in a head-to-head configuration on human chromosome
      2p21 and separated by only 405 bp. Within this short intergenic region, a 243-bp
      GC-rich segment was demonstrated to function as a bidirectional minimal promoter
      to initiate the transcription of both flanking genes. Two key transcription
      factors, NRF-2 and YY-1, were further identified to coordinately participate in
      driving both gene expressions in an additive manner. The functional cooperation
      between these two transcription factors, along with their genomic binding sites
      and some cis-acting repressive elements, are essential for the transcriptional
      activation and tissue distribution of the PREPL-C2ORF34 bidirectional gene pair.
      CONCLUSION: This study provides new insights into the complex transcriptional
      mechanism of a mammalian head-to-head gene pair which requires cooperative
      binding of multiple transcription factors to a bidirectional minimal promoter of
      the shared intergenic region.

PMID- 19575799
TI  - Assessment of smoking status based on cotinine levels in nasal lavage fluid.
AB  - Cotinine is a principal metabolite of nicotine with a substantially longer half
      life, and cotinine levels in saliva, urine or serum are widely used to validate
      self-reported smoking status. The nasal cavity and olfactory system are directly
      exposed to tobacco smoke in smokers and in non-smokers who live with or work
      around smokers. However, despite the potential for a direct impact of tobacco
      smoke on the nasal epithelium and olfactory neurons, no prior studies have
      assessed cotinine levels in nasal mucus. We sought to determine whether cotinine
      levels in nasal lavage fluid (NLF) would provide a reasonable estimate of smoke
      exposure. We assayed cotinine using a competitive immunoassay in NLF from 23
      smokers, 10 non-smokers exposed to tobacco smoke (ETS) and 60 non-smokers who did
      not report smoke exposure. NLF cotinine levels were significantly higher in
      smokers than in non-smokers, regardless of their exposure to ambient tobacco
      smoke. Cotinine levels in this small group of exposed non-smokers were not
      significantly different than those of non-exposed non-smokers. A cutoff of 1
      ng/ml provided a sensitivity of 91% and a specificity of 99% for smoking status
      in this sample. Data were consistent with self-reported smoking status, and a
      cutoff of 1.0 ng/ml NLF cotinine may be used to classify smoking status. While
      saliva is the most easily obtained body fluid, NLF can be used to provide an
      objective and precise indication of smoking status and more directly reflects
      smoke exposure in the nasal and olfactory mucosa.

PMID- 19575800
TI  - Arginine deficiency augments inflammatory mediator production by airway
      epithelial cells in vitro.
AB  - BACKGROUND: Previously we showed that reduced availability of the essential amino
      acid tryptophan per se attenuates post-transcriptional control of interleukin
      (IL)-6 and IL-8 leading to hyperresponsive production of these inflammatory
      mediators by airway epithelial cells. Availability of the non-essential amino
      acid arginine in the inflamed airway mucosa of patients with asthma is reduced
      markedly, but it is not known whether this can also lead to an exaggerated
      production of IL-6 and IL-8. METHODS: IL-6 and IL-8 were determined by ELISA in
      culture supernatants of NCI-H292 airway epithelial-like cells and normal
      bronchial epithelial (NHBE) cells that were exposed to TNF-alpha, LPS or no
      stimulus, in medium with or without arginine. Arginine deficiency may also result
      from exposure to poly-L-arginine or major basic protein (MBP), which can block
      arginine uptake. Epithelial cells were exposed to these polycationic proteins and
      L-(14)C-arginine uptake was assessed as well as IL-6 and IL-8 production. To
      determine the mode of action, IL-6 and IL-8 mRNA profiles over time were assessed
      as were gene transcription and post-transcriptional mRNA degradation. RESULTS:
      For both NCI-H292 and NHBE cells, low arginine concentrations enhanced basal
      epithelial IL-6 and IL-8 production and synergized with TNF-alpha-induced IL-6
      and IL-8 production. Poly-L-arginine enhanced the stimulus-induced IL-6 and IL-8
      production, however, blocking arginine uptake and the enhanced IL-6 and IL-8
      production appeared unrelated. The exaggerated IL-6 and IL-8 production due to
      arginine deficiency and to poly-L-arginine depend on a post-transcriptional and a
      transcriptional process, respectively. CONCLUSION: We conclude that both reduced
      arginine availability per se and the presence of polycationic proteins may
      promote airway inflammation by enhanced pro-inflammatory mediator production in
      airway epithelial cells, but due to distinct mechanisms.

PMID- 19575801
TI  - Quality of life in Brazilian obese adolescents: effects of a long-term
      multidisciplinary lifestyle therapy.
AB  - BACKGROUND: Obesity has adverse physical, social, and economic consequences that
      can negatively affect quality of life (QOL). Thus the aim of this study was to
      verify the effects of a long-term multidisciplinary lifestyle intervention on
      QOL, body image, anxiety, depression and binge eating in obese adolescents.
      METHODS: Sixty-six obese adolescents (41 girls and 25 boys; BMI: 35.62 +/- 4.18
      kg/m2) were recruited from the Multidisciplinary Obesity Intervention Program
      outpatient clinic, and were submitted to a multidisciplinary lifestyle therapy
      (short-term = 12 weeks and long-term = 24 weeks), composed of medical, dietary,
      exercise and psychological programs. Validated self-report questionnaires were
      used to assess symptoms of anxiety Trait/State (STAI); depression (BDI); binge
      eating (BES), body image dissatisfaction (BSQ) and QOL (SF-36). Data were
      analyzed by means of scores; comparisons were made by ANOVA for repeated
      measures, and Turkey's test as post-hoc and Students T test. RESULTS: Long-term
      therapy decreased depression and binge eating symptoms, body image
      dissatisfaction, and improved QOL in girls, whereas, for boys, 24 weeks, were
      effective to reduce anxiety trait/state and symptoms of binge eating, and to
      improve means of dimensions of QOL (p < .05). CONCLUSION: A long-term
      multidisciplinary lifestyle therapy is effective to control psychological aspects
      and to improve QOL in obese adolescents.

PMID- 19575802
TI  - Folksong based appraisal of bioecocultural heritage of sorghum (Sorghum bicolor
      (L.) Moench): a new approach in ethnobiology.
AB  - BACKGROUND: Sorghum is one of the main staple crops for the world's poorest and
      most food insecure people. As Ethiopia is the centre of origin and diversity for
      sorghum, the crop has been cultivated for thousands of years and hence the
      heritage of the crop is expected to be rich. Folksong based appraisal of
      bioecocultural heritage has not been done before. METHODS: In order to assess the
      bioecocultural heritage of sorghum by folksongs various research methods were
      employed. These included focus group discussions with 360 farmers, direct on-farm
      participatory monitoring and observation with 120 farmers, and key informant
      interviews with 60 farmers and development agents. Relevant secondary data was
      also collected from the museum curators and historians. RESULTS: The crop is
      intimately associated with the life of the farmers. The association of sorghum
      with the farmers from seed selection to utilization is presented using folksongs.
      These include both tune and textual (ballad stories or poems) types. Folksongs
      described how farmers maintain a number of varieties on-farm for many biological,
      socio-economic, ecological, ethnological and cultural reasons. Farmers describe
      sorghum as follows: Leaf number is less than twenty; Panicle hold a thousand
      seeds; a clever farmer takes hold of it. In addition, they described the various
      farmers' varieties ethnobotanically by songs. The relative importance of sorghum
      vis-a-vis others crops is similarly explained in folksong terms. CONCLUSION: The
      qualitative description of farmers' characterisation of the crop systems based on
      folksongs is a new system of appraising farmers' bioecocultural heritage. Hence,
      researchers, in addition to formal and quantitative descriptions, should use the
      folksong system for enhanced characterisation and utilization of bioecocultural
      heritages. In general, the salient characteristics of the folksongs used in
      describing the bioecocultural heritages are their oral traditions, varied
      function, communal or individual recreation and message transmissions.

PMID- 19575803
TI  - Expression of HNF4alpha in the human and rat choroid plexus: implications for
      drug transport across the blood-cerebrospinal-fluid (CSF) barrier.
AB  - BACKGROUND: The choroid plexus consists of highly differentiated epithelium and
      functions as a barrier at the interface of the blood-cerebrospinal-fluid (CSF).
      This tissue may therefore determine the bioavailability and transport of drugs to
      the brain. Little is known about the expression of drug and xenobiotic
      metabolizing enzymes (DME) and of drug transporters in the human choroid plexus.
      Notably, the transcription factor and zinc finger protein HNF4alpha is a master
      regulator of DMEs and of drug transporters. As of today its activity in the blood
      CSF barrier is unknown. Here we report our efforts in determining HNF4alpha
      activity in the regulation of ABC transporters in the human and rat choroid
      plexus. RESULTS: We report expression of HNF4alpha by qRT-PCR and by
      immunohistochemistry and evidence transcript expression of the ATP-binding
      cassette transporters ABCB1, ABCB4, ABCC1-6 in choroid plexus. Additionally,
      HNF4alpha DNA binding activity at regulatory sequences of ABCB4 and ABCC1 was
      determined by EMSA bandshift assays with a specific antibody. We then performed
      siRNA mediated functional knock down of HNF4alpha in Caco-2 cells and found ABCC1
      gene expression to be repressed in cell culture experiments. CONCLUSION: Our
      study evidences activity of HNF4alpha in human and rat choroid plexus. This
      transcription factor targets DMEs and drug transporters and may well determine
      availability of drugs at the blood-CSF barrier.

PMID- 19575804
TI  - Nuclear accumulation of polyglutamine disease proteins and neuropathology.
AB  - There are nine inherited neurodegenerative disorders caused by polyglutamine
      (polyQ) expansion in various disease proteins. Although these polyglutamine
      proteins have different functions and are localized in different subcellular
      regions, all the polyQ diseases share a common pathological feature: the nuclear
      accumulation of polyQ disease proteins and the formation of inclusions. The
      nuclear accumulation of polyQ proteins in turn leads to gene transcriptional
      dysregulation and neuropathology. Here we will discuss potential mechanisms
      behind the nuclear accumulation of mutant polyQ proteins, since an understanding
      of how polyQ proteins accumulate in the nucleus could help elucidate the
      pathogenesis of these diseases and develop their treatment.

PMID- 19575805
TI  - Sequence diversity in three tomato species: SNPs, markers, and molecular
      evolution.
AB  - BACKGROUND: Tomato species are of significant agricultural and ecological
      interest, with cultivated tomato being among the most common vegetable crops
      grown. Wild tomato species are native to diverse habitats in South America and
      show great morphological and ecological diversity that has proven useful in
      breeding programs. However, relatively little is known about nucleotide diversity
      between tomato species. Until recently limited sequence information was available
      for tomato, preventing genome-wide evolutionary analyses. Now, an extensive
      collection of tomato expressed sequence tags (ESTs) is available at the SOL
      Genomics Network (SGN). This database holds sequences from several species,
      annotated with quality values, assembled into unigenes, and tested for homology
      against other genomes. Despite the importance of polymorphism detection for
      breeding and natural variation studies, such analyses in tomato have mostly been
      restricted to cultivated accessions. Importantly, previous polymorphisms surveys
      mostly ignored the linked meta-information, limiting functional and evolutionary
      analyses. The current data in SGN is thus an under-exploited resource. Here we
      describe a cross-species analysis taking full-advantage of available information.
      RESULTS: We mined 20,000 interspecific polymorphisms between Solanum lycopersicum
      and S. habrochaites or S. pennellii and 28,800 intraspecific polymorphisms within
      S. lycopersicum. Using the available meta-information we classified genes into
      functional categories and obtained estimations of single nucleotide polymorphisms
      (SNP) quality, position in the gene, and effect on the encoded proteins, allowing
      us to perform evolutionary analyses. Finally, we developed a set of more than
      10,000 between-species molecular markers optimized by sequence quality and
      predicted intron position. Experimental validation of 491 of these molecular
      markers resulted in confirmation of 413 polymorphisms. CONCLUSION: We present a
      new analysis of the extensive tomato EST sequences available that represents the
      most comprehensive survey of sequence diversity across Solanum species to date.
      These SNPs, plus thousands of molecular makers designed to detect the
      polymorphisms are available to the community via a website. Evolutionary analyses
      on these polymorphism uncovered sets of genes potentially important for the
      evolution and domestication of tomato; interestingly these sets were enriched for
      genes involved in response to the environment.

PMID- 19575806
TI  - The association between Colombian medical students' healthy personal habits and a
      positive attitude toward preventive counseling: cross-sectional analyses.
AB  - BACKGROUND: Physician-delivered preventive counseling is important for the
      prevention and management of chronic diseases. Data from the U.S. indicates that
      medical students with healthy personal habits have a better attitude towards
      preventive counseling. However, this association and its correlates have not been
      addressed in rapidly urbanized settings where chronic disease prevention
      strategies constitute a top public health priority. This study examines the
      association between personal health practices and attitudes toward preventive
      counseling among first and fifth-year students from 8 medical schools in Bogota,
      Colombia. METHODS: During 2006, a total of 661 first- and fifth-year medical
      students completed a culturally adapted Spanish version of the "Healthy Doctor =
      Healthy Patient" survey (response rate = 78%). Logistic regression analyses were
      used to assess the association between overall personal practices on physical
      activity, nutrition, weight control, smoking, alcohol use (main exposure
      variable) and student attitudes toward preventive counseling on these issues
      (main outcome variable), stratified by year of training and adjusting by gender
      and medical training-related factors (basic knowledge, perceived adequacy of
      training and perception of the school's promotion on each healthy habit).
      RESULTS: The median age and percentage of females for the first- and fifth-year
      students were 21 years and 59.5% and 25 years and 65%, respectively. After
      controlling for gender and medical training-related factors, consumption of >or=
      5 daily servings of fruits and/or vegetables, not being a smoker or binge drinker
      were associated with a positive attitude toward counseling on nutrition (OR =
      4.71; CI = 1.6-14.1; p = 0.006 smoking (OR = 2.62; CI = 1.1-5.9; p = 0.022), and
      alcohol consumption (OR = 2.61; CI = 1.3-5.4; p = 0.009), respectively.
      CONCLUSION: As for U.S. physician and medical students, a positive association
      was found between the personal health habits of Colombian medical students and
      their corresponding attitudes toward preventive counseling, independent of gender
      and medial training-related factors. Our findings, the first relating to this
      association in medical students in developing regions, also suggest that within
      the medical school context, interventions focused on promoting healthy student
      lifestyles can potentially improve future physician's attitudes toward preventive
      counseling.

PMID- 19575807
TI  - Improved breast cancer survival following introduction of an organized
      mammography screening program among both screened and unscreened women: a
      population-based cohort study.
AB  - INTRODUCTION: Mammography screening reduces breast cancer mortality through
      earlier diagnosis but may convey further benefit if screening is associated with
      optimized treatment through multidisciplinary medical care. In Norway, a national
      mammography screening program was introduced among women aged 50 to 69 years
      during 1995/6 to 2004. Also during this time, multidisciplinary breast cancer
      care units were implemented. METHODS: We constructed three cohorts of breast
      cancer patients: 1) the pre-program group comprising women diagnosed and treated
      before mammography screening began in their county of residence, 2) the post
      program group comprising women diagnosed and treated through multidisciplinary
      breast cancer care units in their county but before they had been invited to
      mammography screening; and 3) the screening group comprising women diagnosed and
      treated after invitation to screening. We calculated Kaplan-Meier plots and
      multivariable Cox proportional hazard models. RESULTS: We studied 41,833 women
      with breast cancer. The nine-year breast cancer-specific survival rate was 0.66
      (95%CI: 0.65 to 0.67) in the pre-program group; 0.72 (95%CI: 0.70 to 0.74) in the
      post-program group; and 0.84 (95%CI: 0.80 to 0.88) in the screening group. In
      multivariable analyses, the risk of death from breast cancer was 14% lower in the
      post-program group than in the pre-program group (hazard ratio 0.86; (95%CI: 0.78
      to 0.95, P = 0.003)). CONCLUSIONS: After nine years follow-up, at least 33% of
      the improved survival is attributable to improved breast cancer management
      through multidisciplinary medical care.

PMID- 19575808
TI  - Novel swing-assist un-motorized exoskeletons for gait training.
AB  - BACKGROUND: Robotics is emerging as a promising tool for functional training of
      human movement. Much of the research in this area over the last decade has
      focused on upper extremity orthotic devices. Some recent commercial designs
      proposed for the lower extremity are powered and expensive - hence, these could
      have limited affordability by most clinics. In this paper, we present a novel un
      motorized bilateral exoskeleton that can be used to assist in treadmill training
      of motor-impaired patients, such as with motor-incomplete spinal cord injury. The
      exoskeleton is designed such that the human leg will have a desirable swing
      motion, once it is strapped to the exoskeleton. Since this exoskeleton is un
      motorized, it can potentially be produced cheaply and could reduce the physical
      demand on therapists during treadmill training. RESULTS: A swing-assist bilateral
      exoskeleton was designed and fabricated at the University of Delaware having the
      following salient features: (i) The design uses torsional springs at the hip and
      the knee joints to assist the swing motion. The springs get charged by the
      treadmill during stance phase of the leg and provide propulsion forces to the leg
      during swing. (ii) The design of the exoskeleton uses simple dynamic models of
      sagittal plane walking, which are used to optimize the parameters of the springs
      so that the foot can clear the ground and have a desirable forward motion during
      walking. The bilateral exoskeleton was tested on a healthy subject during
      treadmill walking for a range of walking speeds between 1.0 mph and 4.0 mph.
      Joint encoders and interface force-torque sensors mounted on the exoskeleton were
      used to evaluate the effectiveness of the exoskeleton in terms of the hip and
      knee joint torques applied by the human during treadmill walking. CONCLUSION: We
      compared two different cases. In case 1, we estimated the torque applied by the
      human joints when walking with the device using the joint kinematic data and
      interface force-torque sensors. In case 2, we calculated the required torque to
      perform a similar gait only using the kinematic data collected from joint motion
      sensors. On analysis, we found that at 2.0 mph, the device was effective in
      reducing the maximum hip torque requirement and the knee joint torque during the
      beginning of the swing. These behaviors were retained as the treadmill speed was
      changed between 1-4 mph. These results were remarkable considering the simplicity
      of the dynamic model, model uncertainty, non-ideal spring behavior, and friction
      in the joints. We believe that the results can be further improved in the future.
      Nevertheless, this promises to provide a useful and effective methodology for
      design of un-motorized exoskeletons to assist and train swing of motor-impaired
      patients.

PMID- 19575809
TI  - A versatile breast reduction technique: conical plicated central U shaped
      (COPCUs) mammaplasty.
AB  - BACKGROUND: There have been numerous studies on reduction mammaplasty and its
      modifications in the literature. The multitude of modifications of reduction
      mammaplasty indicates that the ideal technique has yet to be found. There are
      four reasons for seeking the ideal technique. One reason is to preserve
      functional features of the breast: breastfeeding and arousal. Other reasons are
      to achieve the real geometric and aesthetic shape of the breast with the least
      scar and are to minimize complications of prior surgical techniques without
      causing an additional complication. Last reason is the limitation of the
      techniques described before. To these aims, we developed a new versatile
      reduction mammaplasty technique, which we called conical plicated central U
      shaped (COPCUs) mammaplasty. METHODS: We performed central plication to achieve a
      juvenile look in the superior pole of the breast and to prevent postoperative
      pseudoptosis and used central U shaped flap to achieve maximum NAC safety and to
      preserve lactation and nipple sensation. The central U flap was 6 cm in width and
      the superior conical plication was performed with 2/0 PDS. Preoperative and
      postoperative standard measures of the breast including the superior pole
      fullness were compared. RESULTS: Forty six patients were operated with the above
      mentioned technique. All of the patients were satisfied with functional and
      aesthetic results and none of them had major complications. There were no changes
      in the nipple innervation. Six patients becoming pregnant after surgery did not
      experience any problems with lactation. None of the patients required scar
      revision. CONCLUSION: Our technique is a versatile, safe, reliable technique
      which creates the least scar, avoids previously described disadvantages, provides
      maximum preservation of functions, can be employed in all breasts regardless of
      their sizes.

PMID- 19575810
TI  - Conservation of structure and activity in Plasmodium purine nucleoside
      phosphorylases.
AB  - BACKGROUND: Purine nucleoside phosphorylase (PNP) is central to purine salvage
      mechanisms in Plasmodium parasites, the causative agents of malaria. Most human
      malaria results from infection either by Plasmodium falciparum (Pf), the
      deadliest form of the parasite, or by the widespread Plasmodium vivax (Pv).
      Whereas the PNP enzyme from Pf has previously been studied in detail, despite the
      prevalence of Pv little is known about many of the key metabolic enzymes from
      this parasite, including PvPNP. RESULTS: The crystal structure of PvPNP is
      described and is seen to have many features in common with the previously
      reported structure of PfPNP. In particular, the composition and conformations of
      the active site regions are virtually identical. The crystal structure of a
      complex of PfPNP co-crystallised with inosine and arsenate is also described, and
      is found to contain a mixture of products and reactants - hypoxanthine, ribose
      and arsenate. The ribose C1' in this hybrid complex lies close to the expected
      point of symmetry along the PNP reaction coordinate, consistent with a
      conformation between the transition and product states. These two Plasmodium PNP
      structures confirm the similarity of structure and mechanism of these enzymes,
      which are also confirmed in enzyme kinetic assays using an array of substrates.
      These reveal an unusual form of substrate activation by 2'-deoxyinosine of PvPNP,
      but not PfPNP. CONCLUSION: The close similarity of the Pf and Pv PNP structures
      allows characteristic features to be identified that differentiate the
      Apicomplexa PNPs from the human host enzyme. This similarity also suggests there
      should be a high level of cross-reactivity for compounds designed to inhibit
      either of these molecular targets. However, despite these similarities, there are
      also small differences in the activities of the two Plasmodium enzymes.

PMID- 19575811
TI  - A protocol for classifying normal- and flat-arched foot posture for research
      studies using clinical and radiographic measurements.
AB  - BACKGROUND: There are several clinical and radiological methods available to
      classify foot posture in research, however there is no clear strategy for
      selecting the most appropriate measurements. Therefore, the aim of this study was
      to develop a foot screening protocol to distinguish between participants with
      normal- and flat-arched feet who would then subsequently be recruited into a
      series of laboratory-based gait studies. METHODS: The foot posture of ninety-one
      asymptomatic young adults was assessed using two clinical measurements
      (normalised navicular height and arch index) and four radiological measurements
      taken from antero-posterior and lateral x-rays (talus-second metatarsal angle,
      talo-navicular coverage angle, calcaneal inclination angle and calcaneal-first
      metatarsal angle). Normative foot posture values were taken from the literature
      and used to recruit participants with normal-arched feet. Data from these
      participants were subsequently used to define the boundary between normal- and
      flat-arched feet. This information was then used to recruit participants with
      flat-arched feet. The relationship between the clinical and radiographic measures
      of foot posture was also explored. RESULTS: Thirty-two participants were
      recruited to the normal-arched study, 31 qualified for the flat-arched study and
      28 participants were classified as having neither normal- or flat-arched feet and
      were not suitable for either study. The values obtained from the two clinical and
      four radiological measurements established two clearly defined foot posture
      groups. Correlations among clinical and radiological measures were significant (p
      < 0.05) and ranged from r = 0.24 to 0.70. Interestingly, the clinical measures
      were more strongly associated with the radiographic angles obtained from the
      lateral view. CONCLUSION: This foot screening protocol provides a coherent
      strategy for researchers planning to recruit participants with normal- and flat
      arched feet. However, further research is required to determine whether foot
      posture variations in the sagittal, transverse or both planes provide the best
      descriptor of the flat foot.

PMID- 19575812
TI  - Genome-wide scans using archived neonatal dried blood spot samples.
AB  - BACKGROUND: Identification of disease susceptible genes requires access to DNA
      from numerous well-characterised subjects. Archived residual dried blood spot
      samples from national newborn screening programs may provide DNA from entire
      populations and medical registries the corresponding clinical information. The
      amount of DNA available in these samples is however rarely sufficient for
      reliable genome-wide scans, and whole-genome amplification may thus be necessary.
      This study assess the quality of DNA obtained from different amplification
      protocols by evaluating fidelity and robustness of the genotyping of 610,000
      single nucleotide polymorphisms, using the Illumina Infinium HD Human610-Quad
      BeadChip. Whole-genome amplified DNA from 24 neonatal dried blood spot samples
      stored between 15 to 25 years was tested, and high-quality genomic DNA from 8 of
      the same individuals was used as reference. RESULTS: Using 3.2 mm disks from
      dried blood spot samples the optimal DNA-extraction and amplification protocol
      resulted in call-rates between 99.15% - 99.73% (mean 99.56%, N = 16), and
      conflicts with reference DNA in only three per 10,000 genotype calls. CONCLUSION:
      Whole-genome amplified DNA from archived neonatal dried blood spot samples can be
      used for reliable genome-wide scans and is a cost-efficient alternative to
      collecting new samples.

PMID- 19575813
TI  - Capacity mapping of national ethics committees in the Eastern Mediterranean
      Region.
AB  - BACKGROUND: Ethics issues in the areas of science, technology and medicine have
      emerged during the last few decades. Many countries have responded by
      establishing ethics committees at the national level. Identification of National
      Ethics Committees (NECs) in the Eastern Mediterranean (EM) region and the extent
      of their functions and capacity would be helpful in developing capacity building
      programs that address the needs of these committees. Accordingly, we conducted a
      survey to determine the characteristics of existing NECs in the EM region.
      METHODS: We developed a questionnaire to collect information on different aspects
      of NECs. The questionnaire was sent to the WHO country office in each of the 22
      Member States in the EM region. We used descriptive statistics to analyze the
      data. RESULTS: We obtained responses from 77% (17/22) of the EM countries; 88%
      (15/17) of the countries stated they had NECs. Of these NECs, 40% (6/15) were
      involved in the ethics of science and technology, 73% (11/15) in medical ethics,
      and 93% (14/15) in medical research ethics; 10 NECs stated they reviewed research
      protocols. Of the respondent NECs, 25% (4/15) met at least on a monthly basis.
      Regarding training, 21% of the members from all of the NECs had received formal
      training in ethics; 53% (8/15) of the NECs had none of their members with formal
      training in ethics. Regarding support, 33% (5/15) received financial support and
      60% (9/15) had administrative support. CONCLUSION: While many countries in the EM
      region report the existence of NECs, many meet infrequently, many have members
      without formal training in ethics, and many lack important financial and
      administrative resources. Further efforts should be directed towards capacity
      building programs that include ethics training and provision of important
      infrastructure resources for these committees.

PMID- 19575814
TI  - The impact of avoiding cardiopulmonary by-pass during coronary artery bypass
      surgery in elderly patients: the Danish On-pump Off-pump Randomisation Study
      (DOORS).
AB  - BACKGROUND: Coronary Artery Bypass Graft operation for ischemic heart disease
      provides improved quality of life and, in some patients, prolonged survival.
      Concern has, however, been raised about complications that may be related to the
      use of cardiopulmonary by-pass (CPB) and aortic cross-clamping. It has been
      hypothesized that when coronary artery by-pass grafting is performed without the
      use of CPB, the rate of serious complications is reduced. METHODS/DESIGN: The
      trial is designed as an open, randomized, controlled, clinical trial with blinded
      assessment of end-points. Patients at or above 70 years of age, referred for
      surgical myocardial revascularisation, are included and randomised to receive
      coronary artery by-pass grafting either with or without the use of CPB and aortic
      cross-clamping. Follow-up is performed by clinical, biochemical,
      electrocardiographic, and angiographic data that are evaluated by independent
      committees that are blinded with respect to the result of the randomisation. End
      points include mortality, stroke, myocardial infarction, graft patency, quality
      of life, and cost-effectiveness. The trial is performed in four different Danish,
      cardiac surgery centres. TRIAL REGISTRATION: ClinicalTrials.gov NCT00123981.

PMID- 19575815
TI  - A meta-analysis of the effect of antibody therapy for the prevention of severe
      respiratory syncytial virus infection.
AB  - BACKGROUND: The primary objective of this meta-analytic study was to determine
      the impact of RSV-IGIV and palivizumab on risk of respiratory syncytial virus
      (RSV)-related hospitalization. Secondary objectives were to determine if antibody
      therapy decreases the risk of RSV infection, intensive care admission, mechanical
      ventilation, and mortality in high risk infant populations. METHODS: We performed
      searches of electronic data bases from 1966 to April 2009. Inclusion and
      exclusion criteria were defined a priori. Inclusion criteria were as follows: 1)
      There was randomization between polyclonal or monoclonal antibodies and placebo
      or no therapy, and 2) Polyclonal or monoclonal antibodies were given as
      prophylaxis. RESULTS: Of the six included studies, three utilized RSV-IGIV (total
      of 533 randomized to treatment groups) and three utilized palivizumab (total of
      1,663 randomized to treatment groups). The absolute risk of hospitalization in
      the control arms was 12% and overall RR for all 2,196 children who received one
      of the antibody products was 0.53 (95% CI 0.43, 0.66), P < 0.00001. When looking
      only at the children who received palivizumab, the RR for hospitalization was
      0.50 (95% CI 0.38, 0.66), P < 0.00001. For the children receiving RSV-IGIV, the
      RR for hospitalization was 0.59 (95% CI 0.42, 0.83, P < 0.002). The use of
      palivizumab resulted in a significant decrease in admission to the ICU (RR 0.29
      (95% CI 0.14, 0.59; P = 0.0007). There was no significant reduction in the risk
      of mechanical ventilation or mortality with the use of antibody prophylaxis.
      Infants born at less than 35 weeks gestational age, and those with chronic lung
      and congenital heart disease all had a significant reduction in the risk of RSV
      hospitalization with children born under 35 weeks gestational age showing a trend
      towards the greatest benefit. CONCLUSION: Both palivizumab and RSV-IGIV decrease
      the incidence of RSV hospitalization and ICU admission and their effect appears
      to be qualitatively similarly. There was neither a statistically significant
      reduction in the incidence of mechanical ventilation nor in all cause mortality.
      This meta-analysis separately quantifies the impact of RSV-IGIV and palivizumab
      on various measures of severe RSV disease and builds upon a previous study that
      was only able to examine the pooled effect of all antibody products together.

PMID- 19575816
TI  - Detection of novel insect flavivirus sequences integrated in Aedes albopictus
      (Diptera: Culicidae) in Northern Italy.
AB  - The presence of DNA sequences integrated from a new flavivirus related to Cell
      Fusing Agent and Kamiti River Virus was identified in wild Aedes albopictus
      mosquito populations from the provinces of Trentino and Padova, Northern Italy.
      Field work was developed during August-October 2007 with BG-traps, and mosquitoes
      were screened for flavivirus and alphavirus. No alphavirus was detected,
      indicating that Chikungunya virus is not present in these mosquitoes in Trentino
      and Padova area. However, 21% of the pools were positive for flavivirus, further
      recognised with BLAST as similar to Kamiti River Virus. Phylogenetical analysis
      with 708 nucleotides from the NS5 gene identified this virus as a new member of
      the insect flavivirus clade, together with others like Kamiti River Virus, Cell
      Fusing Agent or Culex flavivirus, and in the group of those transmitted by Aedes.
      Furthermore, the treatment with RNAse, indicated that this flavivirus should be
      integrated in the genome of Ae. albopictus. These results propose that these
      sequences are transmitted by both sexes, and with different prevalence in the
      studied populations, and support the idea of a widespread distribution of
      integrated genomes in several mosquitoes from different areas, as first
      demonstrated with Cell Silent Agent. Evolutionary implications of this discovery
      and application in flavivirus phylogeny are discussed.

PMID- 19575817
TI  - Younger age of escalation of cardiovascular risk factors in Asian Indian
      subjects.
AB  - BACKGROUND: Cardiovascular risk factors start early, track through the young age
      and manifest in middle age in most societies. We conducted epidemiological
      studies to determine prevalence and age-specific trends in cardiovascular risk
      factors among adolescent and young urban Asian Indians. METHODS: Population based
      epidemiological studies to identify cardiovascular risk factors were performed in
      North India in 1999-2002. We evaluated major risk factors-smoking or tobacco use,
      obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre
      specified definitions in 2051 subjects (male 1009, female 1042) aged 15-39 years
      of age. Age-stratified analyses were performed and significance of trends
      determined using regression analyses for numerical variables and Chi2 test for
      trend for categorical variables. Logistic regression was used to identify
      univariate and multivariate odds ratios (OR) for correlation of age and risk
      factors. RESULTS: In males and females respectively, smoking or tobacco use was
      observed in 200 (11.8%) and 18 (1.4%), overweight or obesity (body mass index,
      BMI > or = 25 kg/m2) in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9,
      females > 0.8) in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL
      cholesterol (> or = 130 mg/dl) in 9.4% and 8.9%, low HDL cholesterol (<40 mg/dl
      males, <50 mg/dl females) in 16.2% and 49.7%, hypertriglyceridemia (> or = 150
      mg/dl) in 9.7% and 6%, diabetes in 1.0% and 0.4% and the metabolic syndrome in
      3.4% and 3.6%. Significantly increasing trends with age for indices of obesity
      (BMI, waist, WHR), glycemia (fasting glucose, metabolic syndrome) and lipids
      (cholesterol, LDL cholesterol, HDL cholesterol) were observed (p for trend <
      0.01). At age 15-19 years the prevalence (%) of risk factors in males and
      females, respectively, was overweight/obesity in 7.6, 8.8; high WHR 4.9, 14.4;
      hypertension 2.3, 0.3; high LDL cholesterol 2.4, 3.2; high triglycerides 3.0,
      3.2; low HDL cholesterol 8.0, 45.3; high total:HDL ratio 3.7, 4.7, diabetes 0.0
      and metabolic syndrome in 0.0, 0.2 percent. At age groups 20-29 years in males
      and females, ORs were, for smoking 5.3, 1.0; obesity 1.6, 0.8; truncal obesity
      4.5, 3.1; hypertension 2.6, 4.8; high LDL cholesterol 6.4, 1.8; high
      triglycerides 3.7, 0.9; low HDL cholesterol 2.4, 0.8; high total:HDL cholesterol
      1.6, 1.0; diabetes 4.0, 1.0; and metabolic syndrome 37.7, 5.7 (p < 0.05 for
      some). At age 30-39, ORs were- smoking 16.0, 6.3; overweight 7.1, 11.3; truncal
      obesity 21.1, 17.2; hypertension 13.0, 64.0; high LDL cholesterol 27.4, 19.5;
      high triglycerides 24.2, 10.0; low HDL cholesterol 15.8, 14.1; high total:HDL
      cholesterol 37.9, 6.10; diabetes 50.7, 17.4; and metabolic syndrome 168.5, 146.2
      (p < 0.01 for all parameters). Multivariate adjustment for BMI, waist size and
      WHR in men and women aged 30-39 years resulted in attenuation of ORs for
      hypertension and dyslipidemias. CONCLUSION: Low prevalence of multiple
      cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and
      metabolic syndrome) in adolescents and rapid escalation of these risk factors by
      age of 30-39 years is noted in urban Asian Indians. Interventions should focus on
      these individuals.

PMID- 19575818
TI  - Screening of variants for lactase persistence/non-persistence in populations from
      South Africa and Ghana.
AB  - BACKGROUND: Lactase non-persistence is a condition where lactase activity is
      decreased in the intestinal wall after weaning. In European derived populations a
      single nucleotide polymorphism (SNP) C/T-13910 residing 13.9 kb upstream from the
      lactase gene has been shown to define lactase activity, and several other single
      nucleotide polymorphisms (G/C-14010 T/G-13915, C/G-13907 and T/C-13913) in the
      same region have been identified in African and Middle East populations. RESULTS:
      The T-13910 allele most common in European populations was present in 21.8% mixed
      ancestry (N = 62) individuals and it was absent in the Xhosa (N = 109) and Ghana
      (N = 196) subjects. Five other substitutions were also found in the region
      covering the previously reported variants in African and Middle East populations.
      These included the G/C-14010 variant common in Kenyan and Tanzanian populations,
      which was present in 12.8% of Xhosa population and in 8.1% of mixed ancestry
      subjects. Two novel substitutions (C/T-14091 and A/C-14176) and one previously
      reported substitution G/A-13937 (rs4988234) were less common and present only in
      the Xhosa population. One novel substitution G/A-14107 was present in the Xhosa
      and Ghanaian populations. None of the other previously reported variants were
      identified. CONCLUSION: Identification of the G/C-14010 variant in the Xhosa
      population, further confirms their genetic relatedness to other nomadic
      populations members that belong to the Bantu linguistic group in Tanzania and
      Kenya. Further studies are needed to confirm the possible relationship of the
      novel substitutions to the lactase persistence trait.

PMID- 19575819
TI  - Association between SNPs within candidate genes and compounds related to boar
      taint and reproduction.
AB  - BACKGROUND: Boar taint is an unpleasant odour and flavour of the meat from some
      uncastrated male pigs primarily caused by elevated levels of androstenone and
      skatole in adipose tissue. Androstenone is produced in the same biochemical
      pathway as testosterone and estrogens, which represents a particular challenge
      when selecting against high levels of androstenone in the breeding programme,
      without simultaneously decreasing levels of other steroids. Detection of single
      nucleotide polymorphisms (SNPs) associated with compounds affecting boar taint is
      important both for gaining a better understanding of the complex regulation of
      the trait and for the purpose of identifying markers that can be used to improve
      the gain of breeding. The beneficial SNPs to be used in breeding would have the
      combinational effects of reducing levels of boar taint without affecting
      fertility of the animals. The aim of this study was to detect SNPs in boar taint
      candidate genes and to perform association studies for both single SNPs and
      haplotypes with levels of boar taint compounds and phenotypes related to
      reproduction. RESULTS: An association study involving 275 SNPs in 121 genes and
      compounds related to boar taint and reproduction were carried out in Duroc and
      Norwegian Landrace boars. Phenotypes investigated were levels of androstenone,
      skatole and indole in adipose tissue, levels of androstenone, testosterone,
      estrone sulphate and 17beta-estradiol in plasma, and length of bulbo urethralis
      gland. The SNPs were genotyped in more than 2800 individuals and several SNPs
      were found to be significantly (LRT > 5.4) associated with the different
      phenotypes. Genes with significant SNPs in either of the traits investigated
      include cytochrome P450 members CYP2E1, CYP21, CYP2D6 and CYP2C49, steroid 5alpha
      reductase SRD5A2, nuclear receptor NGFIB, catenin CTNND1, BRCA1 associated
      protein BAP1 and hyaluronoglucosaminidase HYAL2. Haplotype analysis provided
      additional evidence for an effect of CYP2E1 on levels of skatole and indole, and
      for BAP1, HYAL2 and SRD5A2 on levels of androstenone. CONCLUSION: The findings in
      this study indicate that polymorphisms in CYP2E1, CYP21, CYP2D6, CYP2C49, NGFIB
      and CTNND1 might be used to reduce levels of boar taint without affecting levels
      of testosterone, estrone sulphate, 17beta-estradiol or length of bulbo urethralis
      gland.

PMID- 19575820
TI  - Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung
      cancer cell lines.
AB  - BACKGROUND: The Hedgehog (HH) pathway promotes tumorigenesis in a diversity of
      cancers. Activation of the HH signaling pathway is caused by overexpression of HH
      ligands or mutations in the components of the HH/GLI1 cascade, which lead to
      increased transactivation of GLI transcription factors. Although negative kinase
      regulators that antagonize the activity of GLI transcription factors have been
      reported, including GSK3beta, PKA and CK1s, little is known regarding positive
      kinase regulators that are suitable for use on cancer therapeutic targets. The
      present study attempted to identify kinases whose silencing inhibits HH/GLI
      signalling in non-small cell lung cancer (NSCLC). RESULTS: To find positive
      kinase regulators in the HH pathway, kinome-wide siRNA screening was performed in
      a NSCLC cell line, A549, harboring the GLI regulatory reporter gene. This showed
      that p70S6K2-silencing remarkably reduced GLI reporter gene activity. The
      decrease in the activity of the HH pathway caused by p70S6K2-inhibition was
      accompanied by significant reduction in cell viability. We next investigated the
      mechanism for p70S6K2-mediated inhibition of GLI1 transcription by hypothesizing
      that GSK3beta, a negative regulator of the HH pathway, is activated upon p70S6K2
      silencing. We found that phosphorylated-GSK3beta (Ser9) was reduced by p70S6K2
      silencing, causing a decreased level of GLI1 protein. Finally, to further confirm
      the involvement of p70S6K2 in GLI1 signaling, down-regulation in GLI-mediated
      transcription by PI3KCA-inhibition was confirmed, establishing the pivotal role
      of the PI3K/p70S6K2 pathway in GLI1 cascade regulation. CONCLUSION: We report
      herein that inhibition of p70S6K2, known as a downstream effector of the PI3K
      pathway, remarkably decreases GLI-mediated transactivation in NSCLC by reducing
      phosphorylated-GSK3beta followed by GLI1 degradation. These results infer that
      p70S6K2 is a potential therapeutic target for NSCLC with hyperactivated HH/GLI
      pathway.

PMID- 19575821
TI  - A further insight into the biosorption mechanism of Pt(IV) by infrared
      spectrometry.
AB  - BACKGROUND: Platinum nanomaterial is one of the significant noble metal
      catalysts, and the interaction of platinum with microbe is one of the key factors
      in influencing the size and the distribution of the platinum nanoparticles on the
      microbial biomass. Some properties of Pt(IV) adsorption and reduction by resting
      cells of Bacillus megatherium D01 biomass have once been investigated, still the
      mechanism active in the platinum biosorption remains to be seen and requires
      further elucidating. RESULT: A further insight into the biosorption mechanism of
      Pt(IV) onto resting cells of Bacillus megatherium D02 biomass on a molecular
      level has been obtained. The image of scanning electron microscopy (SEM) of the
      D02 biomass challenged with Pt(IV) displayed a clear distribution of bioreduced
      platinum particles with sizes of nanometer scale on the biomass. The state of
      Pt(IV) bioreduced to elemental Pt(0) examined via X-ray photoelectron
      spectroscopy (XPS) suggested that the biomass reduces the Pt(IV) to Pt(II)
      followed by a slower reduction to Pt(0). The analysis of glucose content in the
      hydrolysates of D02 biomass for different time intervals using ultraviolet
      visible (UV-vis) spectrophotometry indicated that certain reducing sugars occur
      in the hydrolyzed biomass and that the hydrolysis of polysaccharides of the
      biomass is a rapid process. The infrared (IR) spectrometry on D02 biomass and
      that challenged with Pt(IV), and on glucose and that reacted with Pt(IV)
      demonstrated that the interaction of the biomass with Pt(IV) seems to be through
      oxygenous or nitrogenous chemical functional groups on the cell wall biopolymers;
      that the potential binding sites for Pt species include hydroxyl of saccharides,
      carboxylate anion and carboxyl of amino acid residues, peptide bond, etc.; and
      that the free monosaccharic group bearing hemiacetalic hydroxyl from the
      hydrolyzed biomass behaving as an electron donor, in situ reduces the Pt(IV) to
      Pt(0). And moreover, the binding of the Pt(IV) to the oxygen of the carbonyl
      group of peptide bond caused a change in the secondary structure of proteins;
      i.e. a transformation, in polypeptide chains, of beta-folded to alpha-helical
      form; it might be expected to be more advantageous than beta-folded form to the
      platinum nanoparticles under shelter from gathering although the both special
      conformations of proteins could be much probably responsible for the
      stabilization of the particles. CONCLUSION: That knowledge could serve as a guide
      in the researches for improving the preparation of highly dispersive supported
      platinum catalyst and for fabricating new advanced platinum nanostructured
      devices by biotechnological methods.

PMID- 19575822
TI  - Substance P scavenger enhances antioxidant defenses and prevents prothrombotic
      effects on the rat lung after acute exposure to oil smoke.
AB  - BACKGROUND: Airborne particulate matter, from cooking oil, smoking, engine
      exhaust and other sources, is associated with the development of atherosclerosis
      and myocardial infarction. In order to explore the cellular and molecular events
      following exposure of rats to lard oil smoke, we measured the generation of
      reactive oxygen species (ROS), substance P, cellular adhesion molecules, and
      thrombosis in relation to inhibitors of substance P, the NK-1 receptor, and
      antioxidants. METHODS: Rats were exposed to oil smoke for 120 min with or without
      20 min pretreatment with lovastatin (substance P scavenger), L733060 (NK-1
      receptor antagonist), vitamin E (antioxidant) or catechins (antioxidant). The
      levels of substance P and ROS were measured. Histological studies observed ROS
      damage in the form of HEL adducts. The prothrombotic effects of oil smoke
      exposure were measured by experimental induction of thrombosis in vivo. RESULTS:
      Oil smoke exposure significantly increased substance P levels, ROS levels, ROS
      damage (HEL adduct levels), and the size of experimentally induced thrombi. The
      pretreatments reduced all of these effects of oil smoke exposure; at many time
      points the reductions were statistically significant. CONCLUSION: We established
      a connection between oil smoke exposure and thrombosis which involves substance P
      and its receptor, the NK-1 receptor, and ROS. This study helps establish a
      mechanistic explanation of how airborne particulate matter can increase the risk
      of cardiovascular illness.

PMID- 19575823
TI  - The scurs inheritance: new insights from the French Charolais breed.
AB  - BACKGROUND: Polled animals are valued in cattle industry because the absence of
      horns has a significant economic impact. However, some cattle are neither polled
      nor horned but have so-called scurs on their heads, which are corneous growths
      loosely attached to the skull. A better understanding of the genetic determinism
      of the scurs phenotype would help to fine map the polled locus. To date, only one
      study has attempted to map the scurs locus in cattle. Here, we have investigated
      the inheritance of the scurs phenotype in the French Charolais breed and examined
      whether the previously proposed localisation of the scurs locus on bovine
      chromosome 19 could be confirmed or not. RESULTS: Our results indicate that the
      inheritance pattern of the scurs phenotype in the French Charolais breed is
      autosomal recessive with complete penetrance in both sexes, which is different
      from what is reported for other breeds. The frequency of the scurs allele (Sc)
      reaches 69.9% in the French Charolais population. Eleven microsatellite markers
      on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib
      families). Both non-parametric and parametric linkage analyses suggest that in
      the French Charolais population the scurs locus may not map to the previously
      identified region. A new analysis of an Angus-Hereford and Hereford-Hereford
      pedigree published in 1978 enabled us to calculate the frequency of the Sc allele
      in the Hereford breed (89.4%) and to study the penetrance of this allele in males
      heterozygous for both polled and scurs loci (40%). This led us to revise the
      inheritance pattern of the scurs phenotype proposed for the Hereford breed and to
      suggest that allele Sc is not fully but partially dominant in double heterozygous
      males while it is always recessive in females. Crossbreeding involving the
      Charolais breed and other breeds gave results similar to those reported in the
      Hereford breed. CONCLUSION: Our results suggest the existence of unknown genetics
      factors modifying the expression of the scurs locus in double heterozygous
      Hereford and Angus males. The specific inheritance pattern of the scurs locus in
      the French Charolais breed represents an opportunity to map this gene and to
      identify the molecular mechanisms regulating the growth of horns in cattle.

PMID- 19575824
TI  - Development of health technology assessment in Lithuania.
AB  - OBJECTIVES: To describe how Lithuania is attempting to develop health technology
      assessment (HTA) structures. METHODS: The case study of the history of
      development of HTA in Lithuania is presented. RESULTS: Historical steps of HTA
      development are as follows: in 1993, a few conferences on HTA; eight people were
      trained in Sweden at SBU; the book First Steps of HTA in Lithuania (5) was issued
      together with SBU in 1993; participation in the International Society of
      Technology Assessment in Health Care (ISTAHC) conferences; participation in
      development of training courses and European networks of HTA; new people in HTA
      were trained in health accreditation service, Sickness Fund, and Ministry of
      Health. The major step was establishment of an evidence-based medicine library.
      In 1994, Article 54 in the Health Care System Law, which declares that the use of
      healthcare technologies that have not been assessed or approved shall be
      prohibited, except in cases provided by law, was passed. The procedure of
      healthcare technologies assessment and approval was to be established by the
      Ministry of Health Care. A policy of HTA was approved with the program for HTA in
      1999 in the Ministry of Health. Currently, enthusiasts of HTA fully realize that
      technology assessment is a developing frontier for creative and constructive
      thinking from all disciplinary view points. CONCLUSIONS: Unfortunately, in this
      country, there is still a very small demand for HTA reports from the decision
      maker's side. Hopefully joining the network of European Union Network for Health
      Technology Assessment (EUnetHTA) will give a new challenge for further policy
      development.

PMID- 19575825
TI  - Health technology assessment development in China.
AB  - OBJECTIVES: This study is to review health technology assessment (HTA)
      development in China during the past two decades, and to facilitate further
      development of HTA and its integration into policy making. METHODS: The study
      depends very much on the extensive experiences of the authors in involvement of
      HTA in China. In addition, literature review and Web site searching have been
      used to trace the process of growth of HTA in China. RESULTS: With its rapid
      economic development, the Chinese health system has had many achievements in the
      past 30 years. However, there are some weaknesses that have developed during this
      period. HTA is traced back to the early 1990s in China. First, HTA knowledge
      transfer and establishment of HTA units were effective ways to develop HTA in
      China. By the end of 1990s, the policy makers of the Ministry of Health (MoH)
      made efforts to merge HTA with policy making to improve the quality and
      efficiency of health care. The main government authorities related to health
      technology are the State Food and Drug Administration, the Ministry of Labor and
      Social Security, and the MoH. Their involvements in HTA are varied. CONCLUSION: A
      technology licensure mechanism based on HTA, including technology permission for
      use, institution licensure, and workforce licensure, is being gradually carried
      out by the MoH in China. Moreover, HTA can play an important role in technology
      market entry, insurance benefit coverage, formulary, clinical pathway,
      reimbursement, and so on. There is a great opportunity for HTA to be an important
      part of health reform, especially to help policy makers within the health sector
      to make difficult decisions.

PMID- 19575827
TI  - Symposium on ultrafast electron microscopy and ultrafast science.

PMID- 19575829
TI  - Ultracold electron source for single-shot, ultrafast electron diffraction.
AB  - Ultrafast electron diffraction (UED) enables studies of structural dynamics at
      atomic length and timescales, i.e., 0.1 nm and 0.1 ps, in single-shot mode. At
      present UED experiments are based on femtosecond laser photoemission from solid
      state cathodes. These photoemission sources perform excellently, but are not
      sufficiently bright for single-shot studies of, for example, biomolecular
      samples. We propose a new type of electron source, based on near-threshold
      photoionization of a laser-cooled and trapped atomic gas. The electron
      temperature of these sources can be as low as 10 K, implying an increase in
      brightness by orders of magnitude. We investigate a setup consisting of an
      ultracold electron source and standard radio-frequency acceleration techniques by
      GPT tracking simulations. The simulations use realistic fields and include all
      pairwise Coulomb interactions. We show that in this setup 120 keV, 0.1 pC
      electron bunches can be produced with a longitudinal emittance sufficiently small
      for enabling sub-100 fs bunch lengths at 1% relative energy spread. A transverse
      root-mean-square normalized emittance of epsilon(x) = 10 nm is obtained,
      significantly better than from photoemission sources. Correlations in transverse
      phase-space indicate that the transverse emittance can be improved even further,
      enabling single-shot studies of biomolecular samples.

PMID- 19575828
TI  - The evolution of ultrafast electron microscope instrumentation.
AB  - Extrapolating from a brief survey of the literature, we outline a vision for the
      future development of time-resolved electron probe instruments that could offer
      levels of performance and flexibility that push the limits of physical
      possibility. This includes a discussion of the electron beam parameters
      (brightness and emittance) that limit performance, the identification of a
      dimensionless invariant figure of merit for pulsed electron guns (the number of
      electrons per lateral coherence area, per pulse), and calculations of how this
      figure of merit determines the trade-off of spatial against temporal resolution
      for different imaging modes. Modern photonics' ability to control its fundamental
      particles at the quantum level, while enjoying extreme flexibility and a very
      large variety of operating modes, is held up as an example and a goal. We argue
      that this goal may be approached by combining ideas already in the literature,
      suggesting the need for large-scale collaborative development of next-generation
      time-resolved instruments.

PMID- 19575830
TI  - Novel radio-frequency gun structures for ultrafast relativistic electron
      diffraction.
AB  - Radio-frequency (RF) photoinjector-based relativistic ultrafast electron
      diffraction (UED) is a promising new technique that has the potential to probe
      structural changes at the atomic scale with sub-100 fs temporal resolution in a
      single shot. We analyze the limitations on the temporal and spatial resolution of
      this technique considering the operating parameters of a standard 1.6 cell RF gun
      (which is the RF photoinjector used for the first experimental tests of
      relativistic UED at Stanford Linear Accelerator Center; University of California,
      Los Angeles; Brookhaven National Laboratory), and study the possibility of
      employing novel RF structures to circumvent some of these limits.

PMID- 19575831
TI  - DC photoelectron gun parameters for ultrafast electron microscopy.
AB  - We present a characterization of the performance of an ultrashort laser pulse
      driven DC photoelectron gun based on the thermionic emission gun design of Togawa
      et al. [Togawa, K., Shintake, T., Inagaki, T., Onoe, K. & Tanaka, T. (2007). Phys
      Rev Spec Top-AC 10, 020703]. The gun design intrinsically provides adequate
      optical access and accommodates the generation of approximately 1 mm2 electron
      beams while contributing negligible divergent effects at the anode aperture. Both
      single-photon (with up to 20,000 electrons/pulse) and two-photon photoemission
      are observed from Ta and Cu(100) photocathodes driven by the harmonics
      (approximately 4 ps pulses at 261 nm and approximately 200 fs pulses at 532 nm,
      respectively) of a high-power femtosecond Yb:KGW laser. The results, including
      the dependence of the photoemission efficiency on the polarization state of the
      drive laser radiation, are consistent with expectations. The implications of
      these observations and other physical limitations for the development of a
      dynamic transmission electron microscope with sub-1 nm.ps space-time resolution
      are discussed.

PMID- 19575832
TI  - Photon-assisted electron energy loss spectroscopy and ultrafast imaging.
AB  - A variety of ways is described in which photons can be used not only for
      ultrafast electron microscopy but also to enormously widen the energy range of
      spatially-resolved electron spectroscopy. Periodic chains of femtosecond laser
      pulses are a particularly important and accurately timed source for single-shot
      imaging and diffraction as well as for several forms of pump-probe microscopy at
      even higher spatial resolution and sub-picosecond timing. Many exciting new
      fields are opened up for study by these developments. Ultrafast, single shot
      diffraction with intense pulses of X-rays supplemented by phase retrieval
      techniques may eventually offer a challenging alternative and purely photon-based
      route to dynamic imaging at high spatial resolution.

PMID- 19575833
TI  - The development and applications of ultrafast electron nanocrystallography.
AB  - We review the development of ultrafast electron nanocrystallography as a method
      for investigating structural dynamics for nanoscale materials and interfaces. Its
      sensitivity and resolution are demonstrated in the studies of surface melting of
      gold nanocrystals, nonequilibrium transformation of graphite into reversible
      diamond-like intermediates, and molecular scale charge dynamics, showing a
      versatility for not only determining the structures, but also the charge and
      energy redistribution at interfaces. A quantitative scheme for 3D retrieval of
      atomic structures is demonstrated with few-particle (<1,000) sensitivity,
      establishing this nanocrystallographic method as a tool for directly visualizing
      dynamics within isolated nanomaterials with atomic scale spatio-temporal
      resolution.

PMID- 19575834
TI  - Nuclear microscopy: a novel technique for quantitative imaging of gadolinium
      distribution within tissue sections.
AB  - All clinically-approved and many novel gadolinium (Gd)-based contrast agents used
      to enhance signal intensity in magnetic resonance imaging (MRI) are optically
      silent. To verify MRI results, a "gold standard" that can map and quantify Gd
      down to the parts per million (ppm) levels is required. Nuclear microscopy is a
      relatively new technique that has this capability and is composed of a
      combination of three ion beam techniques: scanning transmission ion microscopy,
      Rutherford backscattering spectrometry, and particle induced X-ray emission used
      in conjunction with a high energy proton microprobe. In this proof-of-concept
      study, we show that in diseased aortic vessel walls obtained at 2 and 4 h after
      intravenous injection of the myeloperoxidase-sensitive MRI agent, bis-5
      hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium, there was a time
      dependant Gd clearance (2 h = 18.86 ppm, 4 h = 8.65 ppm). As expected, the
      control animal, injected with the clinically-approved conventional agent
      diethylenetriamine-pentaacetate gadolinium and sacrificed 1 week after injection,
      revealed no significant residual Gd in the tissue. Similar to known in vivo Gd
      pharmacokinetics, we found that Gd concentration dropped by a factor of 2 in
      vessel wall tissue in 1.64 h. Further high-resolution studies revealed that Gd
      was relatively uniformly distributed, consistent with random agent diffusion. We
      conclude that nuclear microscopy is potentially very useful for validation
      studies involving Gd-based magnetic resonance contrast agents.

PMID- 19575835
TI  - Zinc mapping and density imaging of rabbit pancreas endocrine tissue sections
      using nuclear microscopy.
AB  - Nuclear microscopy is a suite of techniques based on a focused beam of MeV
      protons. These techniques have the unique ability to image density and structural
      variations in relatively thick tissue sections, map trace elements at the
      cellular level to the microgram per gram (dry weight) level, and extract
      quantitative information on these elements. The trace elemental studies can be
      carried out on unstained freeze-dried tissue sections, thereby minimizing any
      problems of contamination or redistribution of elements during conventional
      staining and fixing procedures. The pancreas is a gland with different
      specialized cells and a complex hormonal activity where trace elements play an
      important role. For example, zinc has an active role in insulin production, and
      calcium ions participate in the stimulation and secretion process of insulin.
      Using nuclear microscopy with a spatial resolution of 1 mum, we have located,
      using zinc mapping, the islets of Langerhans in freeze-dried normal rabbit tissue
      sections. The islets of Langerhans contain beta-cells responsible for insulin
      production. Subsequent quantitative analyses have indicated elevations in most
      elements within the islets of Langerhans, and significantly so for the
      concentrations of Zn [3,300 compared to 90 microg/g (dry weight)] and Ca [1,100
      compared to 390 microg/g (dry weight)].

PMID- 19575836
TI  - Reproducibility of immunostaining quantification and description of a new digital
      image processing procedure for quantitative evaluation of immunohistochemistry in
      pathology.
AB  - Quantification of immunostaining is a widely used technique in pathology.
      Nonetheless, techniques that rely on human vision are prone to inter- and
      intraobserver variability, and they are tedious and time consuming. Digital image
      analysis (DIA), now available in a variety of platforms, improves quantification
      performance: however, the stability of these different DIA systems is largely
      unknown. Here, we describe a method to measure the reproducibility of DIA
      systems. In addition, we describe a new image-processing strategy for
      quantitative evaluation of immunostained tissue sections using DAB/hematoxylin
      stained slides. This approach is based on image subtraction, using a blue low
      pass filter in the optical train, followed by digital contrast and brightness
      enhancement. Results showed that our DIA system yields stable counts, and that
      this method can be used to evaluate the performance of DIA systems. The new image
      processing approach creates an image that aids both human visual observation and
      DIA systems in assessing immunostained slides, delivers a quantitative
      performance similar to that of bright field imaging, gives thresholds with
      smaller ranges, and allows the segmentation of strongly immunostained areas, all
      resulting in a higher probability of representing specific staining. We believe
      that our approach offers important advantages to immunostaining quantification in
      pathology.

PMID- 19575837
TI  - Effects of Clitoria ternatea leaf extract on growth and morphogenesis of
      Aspergillus niger.
AB  - Clitoria ternatea is known for its antimicrobial activity but the antifungal
      effects of leaf extract on growth and morphogenesis of Aspergillus niger have not
      been observed. The extract showed a favorable antifungal activity against A.
      niger with a minimum inhibition concentration 0.8 mg/mL and minimum fungicidal
      concentration 1.6 mg/mL, respectively. The leaf extract exhibited considerable
      antifungal activity against filamentous fungi in a dose-dependent manner with 0.4
      mg/mL IC50 value on hyphal growth of A. niger. The main changes observed under
      scanning electron microscopy after C. ternatea extract treatment were loss of
      cytoplasm in fungal hyphae and the hyphal wall and its diameter became markedly
      thinner, distorted, and resulted in cell wall disruption. In addition,
      conidiophore alterations were also observed when A. niger was treated with C.
      ternatea leaf extract.

PMID- 19575839
TI  - Sudden deafness in a patient with secondary syphilis.
AB  - OBJECTIVES: To emphasise the importance of considering a diagnosis of early
      acquired syphilis in all sexually active adults, and to review the ENT
      manifestations and treatment of acquired syphilis. CASE REPORT: A 24-year-old
      woman presented with sudden hearing loss, and subsequently developed clinical
      features suggestive of secondary syphilis. She was seen in the departments of
      ENT, dermatology, rheumatology and infectious diseases before a correct diagnosis
      was made. Treatment resulted in only partial recovery of hearing. CONCLUSIONS:
      With the exponential rise in syphilis cases in the UK, there has been a re
      emergence of presenting manifestations that had previously become rare. Early
      syphilis should be considered in all sexually active adults who present with
      deafness, as prompt diagnosis and treatment are crucial for maximum recovery.

PMID- 19575840
TI  - Mobile, one stage, bilateral ear surgery for chronic otitis media patients in
      remote areas.
AB  - OBJECTIVES: We evaluated the results of mobile, one stage, bilateral ear surgery
      conducted in Greenland, where chronic otitis media with and without suppuration
      is prevalent. The study aimed to increase the number of operations conducted and
      to reduce the cost of ear surgery in remote areas. MATERIALS AND METHODS: The
      study was longitudinal and prospective, with a two-year follow up. Seventeen East
      Greenlandic patients with bilateral chronic suppurative otitis media or chronic
      otitis media were selected. Their median age was 16 years; 53 per cent were
      female and 47 per cent male. Hearing was assessed using median air conduction
      pure tone average gain, and the 'take rate' (i.e. the percentage of total ears
      with a closed perforation) was evaluated. RESULTS: All patients attended for
      follow up. Eighty-two per cent had at least one perforation closed, and the
      overall take rate was 65 per cent of the 34 ears. The median air conduction pure
      tone average gain after two years was 18 dB and 13 dB for the right and left
      ears, respectively. Fourteen patients (82 per cent) obtained an air conduction
      pure tone average hearing level of < or =25 dB in at least one ear. In total, 71
      per cent of the patients were satisfied. There were no hearing hazards.
      CONCLUSIONS: The results of mobile, one stage, bilateral ear surgery conducted in
      Greenland for long-lasting chronic suppurative otitis media and chronic otitis
      media were acceptable and safe, and more ears underwent surgery at reduced cost
      compared with unilateral ear surgery.

PMID- 19575841
TI  - Ossicular chain reconstruction with a titanium prosthesis.
AB  - OBJECTIVE: Ossicular chain damage from chronic ear disease is a significant
      problem in the Australian population. The ideal ossicular chain reconstruction
      prosthesis has yet to be defined. This paper examines, for the first time, the
      use of a titanium prosthesis for ossicular chain reconstruction in Australian
      patients. STUDY DESIGN: Retrospective chart review. SUBJECTS AND METHODS: All
      patients undergoing ossicular chain reconstruction with a titanium prosthesis
      between 1 February 2002 and 31 March 2007. RESULTS: Results showed a low
      complication rate, with only one extrusion out of 55 cases (1.8 per cent).
      Successful rehabilitation of conductive hearing loss (i.e. to < or =20 dB air
      bone gap) was obtained in 85 per cent of the partial ossicular chain
      reconstruction group and 77 per cent of the total ossicular chain reconstruction
      group. Pure tone thresholds improved by an average 18 dB in the partial
      reconstruction group and 25 dB in the total reconstruction group. CONCLUSION:
      Titanium is an ideal material for ossicular chain reconstruction due to its ease
      of insertion, low rate of extrusion and good functional results.

PMID- 19575842
TI  - Multiple cognitive deficits in patients during the mild cognitive impairment
      stage of Alzheimer's disease: how are cognitive domains other than episodic
      memory impaired?
AB  - BACKGROUND: Little is known about how cognitive domains other than episodic
      memory are affected during the mild cognitive impairment (MCI) stage of
      Alzheimer's disease (AD). We attempted to clarify this issue in this study.
      METHODS: Fifty-seven Japanese subjects were divided into two groups: one
      comprising people in the MCI stage of AD (MCI group, n = 28) and the other of
      normal controls (NC group, n = 29). Cognitive functions were assessed using the
      Japanese version of the neurobehavioral cognitive status examination (J
      COGNISTAT). RESULTS: The MCI group performed significantly worse than the NC
      group on subtests that assessed orientation, confrontational naming, constructive
      ability, episodic memory, and abstract thinking. Three-quarters of the MCI group
      had deficits in memory and other non-mnemonic domains, particularly constructive
      ability and abstract thinking. However, within-subject comparisons showed that
      the MCI group performed significantly worse on the memory subtest compared to any
      other subtest. CONCLUSIONS: Besides episodic memory, multiple non-mnemonic
      cognitive domains, such as constructive ability and abstract thinking, are also
      impaired during the MCI stage of AD; however, these non-mnemonic deficits are
      smaller than episodic memory impairment.

PMID- 19575843
TI  - Analysis of regional congenital cardiac surgical outcomes in Florida using the
      Society of Thoracic Surgeons Congenital Heart Surgery Database.
AB  - BACKGROUND: Florida is the fourth largest state in the United States of America.
      In 2004, 218,045 live babies were born in Florida, accounting for approximately
      1744 new cases of congenital heart disease. We review the initial experience of
      The Society of Thoracic Surgeons Congenital Heart Surgery Database with a
      regional outcomes report, namely the Society of Thoracic Surgeons Florida
      Regional Report. METHODS: Eight centres in Florida provide services for
      congenital cardiac surgery. The Children's Medical Services of Florida provide a
      framework for quality improvement collaboration between centres. All congenital
      cardiac surgical centres in Florida have voluntarily agreed to submit data to the
      Society of Thoracic Surgeons Database. The Society of Thoracic Surgeons and Duke
      Clinical Research Institute prepared a Florida Regional Report to allow detailed
      regional analysis of outcomes for congenital cardiac surgery. RESULTS: The report
      of 2007 from the Society of Thoracic Surgeons Congenital Heart Surgery Database
      includes details of 61,014 operations performed during the 4 year data harvest
      window, which extended from 2003 through 2006. Of these operations, 6,385 (10.5%)
      were performed in Florida. Discharge mortality in the data from Florida overall,
      and from each Florida site, with 95% confidence intervals, is not different from
      cumulative data from the entire Society of Thoracic Surgeons Database, both for
      all patients and for patients stratified by complexity. CONCLUSIONS: A regional
      consortium of congenital heart surgery centres in Florida under the framework of
      the Children's Medical Services has allowed for inter-institutional collaboration
      with the goal of quality improvement. This experience demonstrates, first, that
      the database maintained by the Society of Thoracic Surgeons can provide the
      framework for regional analysis of outcomes, and second, that voluntary regional
      collaborative efforts permit the pooling of data for such analysis.

PMID- 19575844
TI  - MHC class II expression by beta2 integrin (CD18)-positive microglia, macrophages
      and macrophage-like cells in rabbit retina.
AB  - The aim of this study was to investigate the developmental expression of major
      histocompatibility complex class II (MHCII) by microglia and macrophages and
      their relationship to blood vessels in the retina, a representative tissue of the
      central nervous system. Such information is crucial to understanding the role of
      these cells in immune surveillance. Wholemount preparations of retinas from late
      embryonic, postnatal and adult rabbits were subjected to three-colour
      fluorescence microscopy using beta2 integrin (CD18) and MHCII antibodies and
      biotinylated Griffonia simplicifolia B4 isolectin labelling of blood vessels.
      CD18+ cells consistently exhibited characteristics of macrophages or microglia in
      the vascularized and non-vascularized regions of the retina, respectively. At all
      ages, MHCII was expressed by a high proportion of cells in the vascularized
      region, which contained macrophage-like 'parenchymal cells' as well as typical
      perivascular macrophages. MHCII expression by ramified microglia, first detected
      on postnatal day 30, was lower in the peripheral retina and intermediate in the
      avascular region of the myelinated streak. The observed localization of MHCII+
      cells in relation to blood vessels and location-dependent differences in MHCII
      expression point to the possibility that these cells may be distributed
      strategically within the retina to provide multiple lines of defence against
      immune challenge arriving via the retinal vasculature.

PMID- 19575845
TI  - Protective profile of oxcarbazepine against oxygen-glucose deprivation in
      organotypic hippocampal slice culture could involve PI3K cell signaling pathway.
AB  - OBJECTIVE: Brain ischemia results in cellular degeneration and loss of brain
      function. Oxcarbazepine (OXC), one of the newer antiepileptic drugs, has been
      demonstrating its efficacy on wide spectrum neurological disorders. In this
      paper, we investigated the neuroprotective profile of OXC in an in vitro model of
      ischemia, which consists in the exposure of organotypic hippocampal slice
      cultures to oxygen and glucose deprivation. METHODS: OXC (30 microM) was added to
      the medium before and/or during and/or after the oxygen and glucose deprivation
      induction. Cell death was quantified by propidium iodide uptake measurement.
      Immunoblotting was used to detect the phosphorylation of Akt. RESULTS: Our
      results showed a decrease in propidium iodide incorporation when OXC was added
      before oxygen and glucose deprivation, suggesting a neuroprotective effect. This
      effect was prevented when cultures were previously treated with LY294002, an
      inhibitor of phosphoinositide-3-kinase (PI3K) pathway. We also analysed the
      effect of OXC on Akt phosphorylation. Immunoblotting revealed that OXC did not
      induce any change in phosphorylation/activation of Akt. DISCUSSION: Our results
      reinforce the neuroprotective effect of OXC and add some evidence that its
      mechanism may involve the PI3K pathway, suggesting that such effect could be
      upstream Akt. This indicates that with respect to OXC neuroprotective, Akt may
      not play a crucial role in determining cell survival.

PMID- 19575846
TI  - [Biomarkers of glioma: recent advance and potential applications].

PMID- 19575847
TI  - [Detection of chromosomal imbalance in ependymoma by comparative genomic
      hybridization].
AB  - OBJECTIVE: To investigate genomic DNA imbalances in ependymomas (EDMs) and their
      correlations with the tumor histological types, grades, locations, patients'
      gender and age. METHODS: Chromosomal gains and losses in 16 cases of EDM were
      analyzed using comparative genomic hybridization. RESULTS: Chromosomal regional
      gain and loss were found in 15 and 13 of 16 EDM cases respectively including
      totally 24 regional gains and 19 regional losses in all the tumors studied. Both
      regional gains and losses were mostly seen in myxopapillary EDMs (MPE, WHO grade
      I), more commonly seen in cellular EDMs (CE, WHO grade II) and tanycytic EDMs
      (TE, WHO grade II) than in anaplastic EDMs (AE, WHO grade III). Some of the
      regional gains and losses appeared only in one subtype of MPE, CE, TE and AE
      cases resulting in development of specific imbalance profiles of certain subtype
      in these cases. MPE, CE and TE often had +7. Chromosomal +5 occurred only in MPE
      and CE, and -22q was only seen in CE and TE. AE frequently had +1q, but none had
      +5, +7, -4q, -19q and -22q. The frequencies of any regional gain or loss were not
      affected by patients' genders (P > 0.05). Chromosomal +1q and +7p happened
      predominantly in intracranial EDMs with an averagely onset age of <or= 30 years,
      and +7 was only detected in spinal EDMs of patients over 30 years old, the
      differences were statistically significant (P < 0.05). CONCLUSIONS: The
      frequencies of chromosomal imbalances in EDMs decrease as the tumor grade
      increases. Characteristic chromosomal imbalances in each subtype may play an
      important role in determination of histological phenotypes and tumor grades.
      Chromosomal +1q, +5, +7p, +7, -4q, -19q and -22q are alterations which may
      dictate the biological behaviors of these tumors and the patients' prognosis.

PMID- 19575848
TI  - [Brain tumors in patients with intractable epilepsy: a clinicopathologic study of
      35 cases].
AB  - OBJECTIVE: To study the clinicopathologic features of brain tumors occurring in
      patients with medically intractable epilepsy. METHODS: The clinical, radiologic
      and pathologic features of brain tumors occurring in 35 patients with intractable
      epilepsy encountered during the period from January, 2005 to April, 2008 in
      Xuanwu Hospital were retrospectively reviewed. RESULTS: The mean age of seizure
      onset and duration of disease were 14.3-year-old and 8.6 years, respectively.
      Abnormal signals were observed in 94.3% of cases (33/35) by magnetic resonance
      imaging. The histologic types of brain tumors included ganglioglioma (13/35, WHO
      grade I and 6/35, WHO grade II), dysembryoplastic neuroepithelial tumor (3/35,
      WHO grade I), pleomorphic xanthoastrocytoma (3/35, WHO grade II), diffuse
      astrocytoma (1/35, WHO grade II), oligoastrocytoma (1/35, WHO grade II),
      angiocentric glioma (1/35, WHO grade I) and meningioangiomatosis (1/35). The 6
      remaining cases showed features seen in between glioneuronal hamartoma and mixed
      neuronal-glial tumor. Most of these tumors were located in the temporal lobe
      (27/35) and associated with focal cortical dysplasia. Immunohistochemical study
      showed a remarkable expression of CD34 in gangliogliomas. CONCLUSIONS: Brain
      tumors in patients with medically intractable epilepsy are almost always benign
      and located in the temporal lobe. Most of them represent mixed neuronal-glial
      tumors and some show transitional features in-between glioneuronal hamartoma and
      mixed neuronal-glial neoplasm. The similar morphologic pattern and biological
      behavior of glioneuronal hamartoma and mixed neuronal-glial tumor may suggest a
      common pathogenetic mechanism.

PMID- 19575849
TI  - [Pathologic and immunohistochemical study on lethal primary brain stem injury].
AB  - OBJECTIVE: To study the histopathologic changes of primary brain stem injury and
      to investigate their significance in the diagnosis of primary brain stem injury.
      METHODS: Sixty-five autopsy cases died of primary brain stem injury and other
      diseases were enrolled into this study. The cases were subdivided into brain stem
      injury group (n = 25) and control group (including 20 cases died of
      cardiovascular disease and 20 cases died of non-cardiovascular diseases). The
      brain stem tissue sections were stained with hematoxylin-eosin and silver
      impregnation techniques. Immunohisto chemical study for glial fibrillary acidic
      protein, neurofilament, amyloid-beta and myelin basic protein was carried out.
      The widest cross diameters of 10 axons highlighted by immunostaining were
      measured in each low power field (x 100) through light miscroscopy in all the
      cases studied. RESULTS: In comparing with that of the control group, there were
      differences in the degree of contusion lesion, reactive astrocytosis, edema and
      pathologic changes of neuronal cells present in the brain stem injury group and
      was statistically significant (P < 0.05). The axons locating in the brain stem
      injury group showed a distinctive histology by the appearance of significantly
      larger diameters (P < 0.05). CONCLUSIONS: Primary brain stem injury demonstrates
      certain distinctive histopathologic changes and measurement of axonal diameters
      provides an additional quantitative index useful in autopsy diagnosis.

PMID- 19575850
TI  - [Olfactory neuroblastoma with unusual structures: a clinical pathologic study].
AB  - OBJECTIVE: To investigate unusual pathological features of olfactory
      neuroblastoma (ONB) and its correlation with the clinical prognosis. METHODS:
      Totally 40 cases of ONB were studied using histology and immunohistochemistry
      techniques. All the cases of ONB were graded according to Hyams Grading system.
      RESULTS: ONB consisted of small round tumor cells growing in nests or lobules
      separated by fibrovascular septa. Characteristically, there were neurofibrillary
      intercellular matrices and Homer-Wright or Flexner-Wintersteiner rosette
      formation. The unusual structures including epithelial components such as mucous
      or squamous cell nests which were found in 45.0% (18/40), and 15.0% (6/40)
      respectively. In addition, 3 cases showed an in-situ form with invasion of tumor
      into olfactory epithelium, and there was exogenous papillary proliferation seen
      in 2 cases. Log-rank survival analysis demonstrated that Hyams Grading had no
      statistical correlation with the prognosis. The presence of necrosis was
      correlated with a poor prognosis (P = 0.016) while the presence of mucous cells
      was correlated with a good prognosis (P = 0.011). CONCLUSIONS: Unusual
      pathological structures including epithelial structures, in-situ invasion of
      tumor tissue into the involving olfactory epithelium and exogenous papillary
      proliferation can be found in ONB, suggesting that ONB may originate from the
      undifferentiated basal cells of olfactory epithelium, through bipotential
      differentiation. The presence of tumor necrosis in ONB is a poor prognostic
      indicator while the presence of mucous cells suggests a good prognosis.

PMID- 19575851
TI  - [Clinicopathologic characteristics of hemangiopericytoma/solitary fibrous tumor
      with giant cells].
AB  - OBJECTIVE: To study the pathological characteristics, diagnosis and differential
      diagnoses of hemangiopericytoma-solitary fibrous tumor with giant cells. METHODS:
      Pathological characteristics of seven cases of orbital and extraorbital
      hemangiopericytoma-solitary fibrous tumors with giant cells were evaluated by HE
      and immunohistochemistry (EnVision method). RESULTS: Two cases were located in
      the orbit, one of which had recurred. Five cases were located in the extraorbital
      regions. Histologically, the tumors were well-circumscribed and composed of non
      atypical, round to spindle cells with collagen deposition in the stroma. The
      tumors had prominent vasculatures and in areas, pseudovascular spaces lined by
      multinucleated giant cells lining which were also present in the stroma.
      Immunohistochemically, both neoplastic cells and multinucleate giant cells
      expressed CD34. Seven patients underwent tumor excision and were well and without
      tumor recurrence upon the clinical follow-up. CONCLUSIONS: Hemangiopericytoma
      solitary fibrous tumor with giant cells is an intermediate soft tissue tumor. It
      typically involves the orbital or extraorbital regions. Histologically, the tumor
      should be distinguished from giant cell fibroblastoma, pleomorphic hyalinzing
      angiectatic tumor of soft part and angiomatoid fibrous histiocytoma.

PMID- 19575853
TI  - [Morphologic and immunophenotypic analysis of angioimmunoblastic T-cell
      lymphoma].
AB  - OBJECTIVE: To study the morphologic and immunophenotypic features of
      angioimmunoblastic T-cell lymphoma (AITL), as well as the origin of the
      proliferative follicular dendritic cells (FDCs) in AITL. METHODS:
      Immunohistochemical study for CD10, CXCL13, bcl-6 and CD21 was performed on 29
      cases of AITL. Double immunostaining for bcl-6/CD3, CD10/CD21 and CD10/CD20 were
      also carried out. Cases of peripheral T-cell lymphoma, unspecified, extranodal
      NK/T-cell lymphoma, nasal-type, enteropathy-type T-cell lymphoma, anaplastic
      large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma and reactive
      lymphoid proliferation were selected as controls. RESULTS: Amongst the 29 cases
      of AITL studied, 75.9% (22/29) showed aberrant expression of CD10, while all
      except one of the controlled cases were negative, 82.8% (24/29) of the AITL cases
      expressed CXCL13, while all cases of peripheral T-cell lymphoma, unspecified were
      negative. As for bcl-6 staining, although the highest percentage of bcl-6
      positive cells was observed in AITL, the expression pattern was not useful in
      differentiating AITL from peripheral T-cell lymphoma, unspecified and lymphoid
      reaction. Besides, all cases of AITL demonstrated the characteristic
      proliferation of follicular dendritic cells. Two of the cases, which contained
      obvious germinal centers, had the follicular dendritic cell meshwork extending
      beyond the lymphoid follicles. CONCLUSIONS: As compared with bcl-6, CD10 and
      CXCL13 are specific and sensitive markers in diagnosing AITL. Part of the
      proliferative FDCs in AITL may originate from the germinal centers.

PMID- 19575854
TI  - [Relationship between hedgehog signaling pathway molecules and HPV16 infection in
      uterine cervical cancers].
AB  - OBJECTIVE: To investigate the significance of sonic hedgehog (Shh), indian
      hedgehog (Ihh), smoothened (Smo) and patched (Ptch) expressions in uterine
      cervical lesions and their relationships with HPV type 16 infection. METHODS:
      Totally 183 cases of cervical lesions, including 32 non-neoplastic cervix, 71
      cervical intraepithelial neoplasia (28 CINI, 18 CINII, and 25 CINIII) and 80
      squamous cell carcinomas (SCC) were selected from the Department of Pathology,
      Yanbian University Hospital, Yanbian Women Hospital, and Yanbian Tumor Hospital.
      Shh, Ihh, Ptch and Smo proteins expression were investigated by
      immunohistochemistry using tissue microarry platform, and the presence of HPV
      type 16 was detected by PCR method. RESULTS: Immunohistochemical staining showed
      that the frequencies of Shh, Ihh, Ptch and Smo expression were rare in normal
      cervical epithelium, but were strongly expressed in cervical cancer and its
      precursor lesions (CINII/III) (P < 0.01, P < 0.01, P < 0.05, P < 0.05,
      respectively). In cervical cancer, the expression rate of Shh (95%) was higher
      than that of CIN (CINI to CINIII) (46.4%, 61.1%, 80.0%, respectively, P < 0.05).
      HPV16 was positive in 77.5% of SCC. In cervical cancer, the expression of Shh was
      related with HPV16 infection (P < 0.05), and the expression of Smo was correlated
      with lymph node metastasis (P < 0.05). CONCLUSIONS: Shh, Ihh, Ptch, and Smo genes
      may play important roles in the development of cervical cancer. Detection of
      Hedgehog signaling pathway molecules seems helpful for the early diagnosis of
      cervical cancer and its precursor lesions, and are potentially therapeutic
      targets as well.

PMID- 19575855
TI  - [Azidothymidine inhibition of telomerase activity and proliferation of TJ905
      human glioblastoma cells].
AB  - OBJECTIVE: To investigate the pharmacological effects and underlying mechanism of
      azidothymidine (AZT) on human glioblastoma cells in vitro. METHODS: The
      telomerase activity of human glioblastoma TJ905 cells was determined by TRAP
      assay after 24 hrs' incubation with 50, 100, 200 micromol/L AZT and control
      vehicle solution. Colony formation efficiencies of the cells were recorded. Cells
      of the 1st, 3rd and 6th generations were harvested, followed by evaluations of
      cyclin A protein expression by Western blot, cell cycle distribution by flow
      cytometry, apoptotic level by single cell gel electrophoresis and proliferation
      index by Ki-67 immunocytochemical staining. RESULTS: AZT inhibited telomerase
      activity of TJ905 cells. Cyclin A expression levels in the cells treated with 50
      and 100 micromol/L AZT were significantly lower than controls (P < 0.01), and
      down-regulation of the expression was in a dose- and time-dependent manner.
      Compared with controls, G(0)/G(1) phase cells were obviously decreased (P < 0.05
      approximately 0.01) and S phase cells significantly increased (P < 0.05
      approximately 0.01) after treatment with 50, 100 and 200 micromol/L AZT. The cell
      numbers of G(0)/G(1) and S phases at the 1st generation of above three treated
      groups changed in a dose-dependent manner, whereas S phase cells increases in all
      AZT treatment groups and G(0)/G(1) phase cell decrease in group treated with 50
      micromol/L AZT were also in a time-dependent manner. Both the apoptotic cells of
      the 1st and 6th generations of all AZT treatment groups were significantly more
      than controls (P < 0.05 approximately 0.01), their numbers of the 6th generations
      of the three groups increased with AZT concentration (P < 0.05 approximately
      0.01), and all of them were more than the 1st and 3rd generations of the same
      dosage group (P < 0.05 approximately 0.01). Colony formation efficiencies and Ki
      67 labeling indexes of the three AZT treatment groups were distinctly lower than
      controls (P < 0.01), and they were also decreased with the elevation of AZT
      concentration and/or the elongation of the incubating time. The difference of any
      above parameter had no significance among the 1st, 3rd and 6th generations of
      control group (P > 0.05). CONCLUSION: AZT blocks S/G(2) conversion of TJ905 cells
      by inhibition of telomerase activity and cyclin A expression, leading to an
      enhancement of apoptosis and suppression of cell proliferation.

PMID- 19575856
TI  - [Endoscopic retrograde cholangiopancreatography-guided brush cytology diagnosis
      of pancreatobiliary tumors].
AB  - OBJECTIVE: To study the cytologic features of pancreatobiliary tumors in
      endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing
      preparations and to evaluate the usefulness of cytology in the diagnosis of
      pancreatobiliary malignancy. METHODS: A retrospective analysis of 212 cases of
      ERCP-guided brush cytology smears performed during the period from January, 2004
      to December, 2006. The cytologic diagnosis was confirmed either by the histologic
      diagnosis or the strict clinical criteria. RESULTS: Two of the cases studied were
      unsatisfactory for diagnosis, with no epithelial cells identified. One hundred
      and thirty-seven smears were diagnosed as "negative", 45 of which subsequently
      confirmed to be malignant (negative predictive value = 60.2%). Six of the 11
      cases with "low-grade atypia" were proven to be malignant (positive predictive
      value = 54.5%), as compared to 19 of 23 cases of "high-grade atypia" (positive
      predictive value = 86.4%). All of the 41 cases with cytologic diagnosis of
      "malignancy" were confirmed to be malignant (positive predictive value = 100%).
      The cytologic features of malignancy in ERCP-guided brushing preparations
      included overlapping nuclei, anisonucleosis, coarse chromatin pattern, poor
      cellular cohesion, tumor diathesis, prominent nucleoli and atypical mitotic
      figures. CONCLUSIONS: The accuracy of ERCP-guided brush cytology relies on good
      specimen preparation and application of morphologic criteria. Grading of
      cytologic atypia is of clinical significance. A "negative" or "low-grade atypia"
      cytologic diagnosis requires further diagnostic workup to rule out the
      possibility of underlying malignancy, while a "high-grade atypia" or "malignant"
      diagnosis is relatively specific in guiding subsequent management of suspected
      pancreatobiliary malignancy.

PMID- 19575857
TI  - [Naso-oropharyneal chordoma: a clinicopathological analysis of 12 cases].

PMID- 19575858
TI  - [Space-occupying lesion of the left occipital lobe].

PMID- 19575859
TI  - [Cystic mass in left temporal bone].

PMID- 19575860
TI  - [Papillary glioneuronal tumor: report of a case].

PMID- 19575861
TI  - [Tubulovillous adenoma of vagina: report of a case].

PMID- 19575862
TI  - [Sarcomatoid carcinoma in urinary bladder: report of a case].

PMID- 19575863
TI  - [Extraskeletal mesenchymal chondrosarcoma of nasal cavity: report of a case].

PMID- 19575864
TI  - [Pyothorax-associated lymphoma: report of a case].

PMID- 19575865
TI  - [Application of new immunohistochemical markers in diagnosis of central nervous
      system tumors].

PMID- 19575868
TI  - [Importance of diagnosis and research on bone and joint pathology].

PMID- 19575866
TI  - [Regulation of transcription factor activator protein 1 cell signaling in tumor
      stroma interaction].

PMID- 19575869
TI  - [Abnormal expression of c-myc, p53, p16 protein and GNAS1 gene mutation in
      fibrous dysplasia].
AB  - OBJECTIVE: To study the significance of c-myc, p53 and p16 protein expression in
      fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to
      explore the property of fibrous dysplasia. METHODS: The expression of c-myc, p53
      and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of
      fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20
      control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA
      extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene
      mutation in 35 cases of fibrous dysplasia. RESULTS: C-myc protein
      immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with
      the negative control group, the difference was significant. P16 positive was
      detected in 34 FD cases (P = 0.001). The difference was significant as compared
      with the positive control group. Positive p53 protein expression was detected in
      the only 1 case of fibrous dysplasia with malignant transformation. PCR
      amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were
      detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud
      syndrome, 1 case was a monostotic lesion. CONCLUSIONS: C-myc could be another
      protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein
      overexpression could be useful in the diagnosis of FD malignancy and in the
      prediction of the prognosis of FD. The abnormal expression of the gene p16 might
      play an important role in the formation of FD. The GNAS1 mutation exist in FD.
      All of the results indicate that FD could be a neoplasia disease, caused by
      multiple factors leading to a dysfunction of bone development.

PMID- 19575870
TI  - [Clinicopathological study of 5 cases of proximal-type epithelioid sarcoma].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis and
      differential diagnoses of proximal-type epithelioid sarcoma (PES). METHODS: Five
      cases of PES were retrieved from pathology files. Clinical, pathologic and
      immunohistochemical features of the tumors were reviewed. RESULTS: One patient
      was female and 4 were male. Ages of the patients ranged from 19 to 46 years. The
      sites of the tumor involvement were vulvar (2 cases), hypogastric zone (1 case),
      anterosuperior iliac spine (1 case) and buttock (1 case). Clinically, the tumor
      masses were painless and progressive solitary nodules. Microscopically, the tumor
      cell growth was infiltrative in nature, nodular in appearance with degenerative
      and necrotic cells at the central areas. The tumors consisted of relatively
      uniform epithelioid cells with round or oval nuclei and eosinophilic cytoplasm.
      Immunohistochemically, the tumor cells were positive for vimentin (5/5), CK
      (4/5), EMA (4/5), beta-catenin (3/5), CD34 (3/5), and S-100 protein (1/5), but
      were negative for SMA, MyoD1, Desmin, HMB-45, CK7 and CK20. CONCLUSION:
      Definitive diagnosis of PES relies on its histopathological characteristics in
      conjunction with appropriate immunohistochemical findings.

PMID- 19575871
TI  - [Low-grade fibromyxoid sarcoma: a clinicopathological analysis of 9 cases].
AB  - OBJECTIVE: To study the clinicopathological features, immnophenotype and
      differential diagnosis of low-grade fibromyxoid sarcoma (LGFMS). METHODS: The
      clinical, radiological and pathological features of 9 cases of LGFMS were
      reviewed. RESULTS: The patients consisted of six males and three females with
      ages ranging from 11 to 65 years (mean 31.4 years). Clinically, most cases
      presented as slowly growing painless masses located in the extremities, trunk and
      neck. Two cases had a history of a rapid recent enlargement. Three cases
      presented with recurrent diseases after incomplete resection. Ultrasound showed
      heterogeneous signal. Precontrast CT and T1-weighted MRI showed a nodular mass of
      low to isodensity, while contrast-enhanced CT and T2-weighted MRI demonstrated
      contrasting zonal areas of hypo/hyperintensity. The tumors measured 3 to 16 cm
      (mean 7.7 cm), with a fibrous to myxoid appearance on cut surface.
      Histologically, they were composed of alternating collagenous and myxoid areas. A
      transition between the two areas could be identified. Giant rosette-like
      structures were observed in 3 cases. The center of the giant rosettes was
      composed of eosinophilic collagen, which showed centrifugal in arrangement. There
      was also gradual transition between the giant rosettes and the fibromyxoid
      component. On high magnification, the tumor was composed of ovoid to spindle
      shaped cells with hyperchromatic nuclei. Nuclear atypia was inconspicuous. The
      tumor cells were arranged mostly in interlacing fascicles or whorls. Vessels were
      not prominent and necrosis was absent. Immunohistochemically, the tumor cells
      showed unique staining for vimentin, consistent with a fibroblastic
      differentiation. CONCLUSIONS: LGFMS is a distinctive low grade fibroblastic
      sarcoma of young adults. Recognizing the characteristics of the rare entity may
      help to avoid misdiagnosis. Wide local excision is recommended to avoid local
      recurrences.

PMID- 19575872
TI  - [Solitary plasmacytoma of spine: a clinical, radiologic and pathologic study of
      13 cases].
AB  - OBJECTIVE: To study the clinical, radiologic and pathologic features of solitary
      plasmacytoma of spine. METHODS: The clinical, radiologic and pathologic features,
      as well as treatment and follow-up data, of 13 solitary plasmacytoma of spine
      cases were retrieved and analyzed. Immunohistochemical study using EnVision
      method for LCA, CD19, CD20, CD79a, CD3, CD7, PC, MUM1, CD138, IgG, IgM, kappa,
      lambda and Ki-67 was carried out. RESULTS: All the tumours were primarily located
      in the vertebrae (including 9 cases in thoracic vertebrae and 4 cases in lumbar
      vertebrae). The male-to-female ratio was 3.3:1. The age of the patients ranged
      from 42 to 69 years (mean age = 56 years). The commonest symptom was pain in the
      surrounding regions. The degree of neurologic disturbance mostly depended on the
      extent of vertebral destruction and structural instability of the spine.
      Radiologic examination showed mainly osteolytic lesions in vertebrae. Magnetic
      resonance imaging demonstrated the presence of heterogeneous intensity inside the
      involved vertebrae (low in T1 weighted and high in T2 weighted images).
      Histologic examination showed diffuse infiltration by malignant cells. In well
      differentiated plasmacytomas, the tumor cells resembled normal plasma cells. In
      poorly differentiated examples, the cellular morphology mimicked that of the
      centroblasts. The interstitial stroma was scanty and contained plenty of vessels,
      sometimes with formation of blood lakes. Amyloid deposition was present in some
      of the cases. Immunohistochemical study showed that the tumor cells were positive
      for CD79a and negative for CD20. Light chain restriction was detected in all the
      13 cases studied. Plasma cell marker PC was expressed in all cases, while IgG was
      positive in 5 cases, IgM in 1 case, MUM1 in 10 cases and CD138 in 8 cases. Ki-67
      index varied from 10% to 50%. All cases were operated, with adjuvant chemotherapy
      and radiotherapy given. CONCLUSIONS: Correlation of clinical, radiologic and
      pathologic features is important in diagnosis of solitary plasmacytoma of spine.
      The possibility of multiple myeloma needs to be excluded. Early detection by
      radiologic examination, local surgical resection, post-operative
      chemoradiotherapy and long-term follow-up are prudent for successful management
      of this condition.

PMID- 19575873
TI  - [Giant cell tumor of bone and malignancies in giant cell tumor: a
      clinicopathologic analysis].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnosis and differential
      diagnosis of malignancies in giant cell tumor (MGCT). METHODS: The
      clinicopathologic features of 13 cases of MGCT were retrospectively reviewed.
      RESULTS: Thirteen cases of MGCT were found amongst a total of 603 cases of giant
      cell tumor encountered. Six of the 13 cases represented concurrent malignancy in
      giant cell tumor while the remaining 7 cases was malignant transformation in
      recurrent giant cell tumor. The age of the patients ranged from 21 to 71 years
      (mean age = 39.5 years) in the first group and from 27 to 52 years (mean age =
      36.7 years) in the second group. In concurrent MGCT, a high-grade sarcoma
      component was present in conjunction with the giant cell tumor component. In
      malignant transformation of recurrent giant cell tumor, the original tumor was
      giant cell tumor and the recurrence showed features reminiscent of malignant
      fibrous histiocytoma. CONCLUSIONS: The diagnosis of malignancies in giant cell
      tumor requires correlation of clinical, radiologic and pathologic features. The
      entities need to be distinguished from other giant cell-rich tumors including
      primary malignant fibrous histiocytoma and giant cell osteosarcoma.

PMID- 19575874
TI  - [Clinicopathologic features and prognostic significance of basal-like breast
      cancer].
AB  - OBJECTIVE: To analyzed a large group of invasive breast cancers with long-term
      follow-up information to evaluate the clinicopathologic, morphological and
      prognostic features of basal-like breast cancers in Chinese population. METHODS:
      Immunohistochemistry was used to detect the expression of ER, HER2, CK5/6, EGFR
      on tissue microarray with 1311 invasive breast cancers. Based on the results,
      these cases were categorized into luminal A, luminal B, basal-like, HER2
      overexpressing and null subtypes. Clinicopathological features and survival rates
      were compared between these groups. RESULTS: Basal-like breast cancers
      constituted 17.0% of 1311 invasive breast cancers with a significantly larger
      size, higher grade and higher incidence of the medullary carcinoma, frequent
      recurrence and infrequent node metastasis. Morphologically, basal-like breast
      cancers showed a significantly more solid architecture and ribbon-like
      architecture associated with necrosis (more geographic necrosis) and central
      scar, a more pushing margin, lymphocytic infiltration and a higher mitosis score,
      more syncytial growth, presence of basaloid cells, spindle cells and squamous
      metaplasia. The disease-free survival and overall survival of basal-like breast
      cancers were significantly poorer than that of luminal A subtype, but similar to
      the other ER-negative subtypes. Basal markers were not independent prognostic
      factors. CONCLUSIONS: Basal-like breast cancers in Chinese population has a
      similar prevalence to that of the western populations. They have distinct
      clinicopathologic features compared to other non-basal breast cancers, but
      overlapping with other ER-negative breast cancers. Morphological features are
      strongly associated with basal-like breast cancers although they are not very
      specific. The survival of basal-like breast cancers is poorer than luminal A, but
      similar to the other ER-negative breast cancers, and basal markers are not
      independent prognostic factors of breast cancers.

PMID- 19575875
TI  - [Small cell variant of peripheral T-cell lymphoma, not otherwise specified: a
      clinicopathologic and immunophenotypic analysis].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      small cell variant of peripheral T-cell lymphoma, not otherwise specified (PTCL,
      NOS). METHODS: The clinicopathologic features of 5 cases of small cell variant of
      PTCL, NOS were retrospectively reviewed, with immunohistochemical study, T-cell
      receptor (TCR) gene rearrangement analysis and evaluation for Epstein-Barr virus
      (EBV) status. RESULTS: All the 5 patients were males. The mean age was 52.6
      years. The median duration before diagnosis was 1 month. Clinically, 3 patients
      presented in stage IV and 2 in stage III. Four of them had generalized
      lymphadenopathy and splenomegaly. Hepatomegaly and massive effusion were found in
      1 and 2 cases, respectively. Marrow involvement was detected in 3 of the 4
      patients with bone marrow biopsy performed and one of them also accompanied by
      lymphocytosis. Histologically, the involved lymph nodes showed partial or
      complete effacement of nodal architecture and replacement by a monomorphous
      population of small lymphoid cells. Scanty large lymphoid cells were also
      identified in 4 cases. Increase in number of blood vessels was noticed in two of
      them as well. Immunohistochemically, the lymphoma cells in all cases expressed
      two or more of the T-cell markers and CD43. The staining for CD20, TdT, CD56 and
      granzyme B was negative. CD99 expression was noted in 3 of the 4 cases. The Ki-67
      index ranged from 5% to 15%. Clonal TCRgamma gene rearrangement was detected in
      the 4 cases studied and one of them also showed TCRbeta gene rearrangement. In
      situ hybridization for EBV-encoded RNA was negative in the 4 cases studied.
      Follow up information was available in 3 of the 5 cases. All of the 3 patients
      died of the disease, with an average survival of 21.7 months. CONCLUSION: Small
      cell variant of PTCL, NOS represents a rare disease entity which often presents
      in advanced tumor stage and carries a poor prognosis.

PMID- 19575876
TI  - [Clinical significance of ZAP-70 protein expression in chronic lymphocytic
      leukemia/small lymphocytic lymphoma].
AB  - OBJECTIVE: To study the clinicopathologic features and prognostic significance of
      ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic
      lymphoma (CLL/SLL). METHODS: The histologic features of 52 cases of CLL/SLL with
      lymph node and/or bone marrow biopsies performed were retrospectively reviewed.
      Immunohistochemical study using EliVision for ZAP-70 protein was adopted.
      RESULTS: The lymph nodes of the 12 cases studied showed effacement of the nodal
      architecture and was replaced by a monotonous infiltration of small lymphoid
      cells. Among them, proliferation centers were identified in 6 cases. Similar
      morphologic pattern was seen in the 40 bone marrow biopsy samples, but no
      proliferation center formation obtained. The infiltration pattern of tumor cells
      in the bone marrow were further subdivided into nodular (n = 9), interstitial (n
      = 3), mixed (n = 9) and diffuse types (n = 19). There was no significant
      difference found on survival rates between the diffuse infiltration and non
      diffuse infiltration groups (Fisher's exact test, P = 0.199). ZAP-70 protein was
      mainly located in the cytoplasm and nuclei of lymphoma cells. There were 21 cases
      (40.4%) positive for ZAP-70 and among them, 11 died of this disease or the
      related infections. On the other hand, ZAP-70 was negative in 31 cases (59.6%)
      and only 4 of them died of this disease or related infections. The overall
      survival in ZAP-70-negative group was higher than that of the ZAP-70-positive
      group (59 months versus 39 months, chi(2) = 6.991, P = 0.008). Follow-up
      information was available in 51 patients. Among the 21 dead cases, 15 died of
      CLL/SLL or the related infection. CONCLUSION: A positive expression of ZAP-70
      protein in CLL/SLL suggests a poor prognosis.

PMID- 19575877
TI  - [Clinicopathologic analyses of non-compaction of ventricular myocardium].
AB  - OBJECTIVE: To investigate the clinicopathologic manifestations of non-compaction
      of ventricular myocardium (NVM). METHODS: Clinical data, electrocardiograms,
      echocardiography images and pathologic changes were studied in five cases of non
      compaction of ventricular myocardium. RESULTS: The patient's ages ranged from 29
      to 57 years old, all were males. Abnormal electrocardiograms were obtained in all
      of the 5 cases. Among them, 3 were diagnosed using echocardiography.
      Histopathologic examination showed that there were abnormally coarse muscle
      trabeculation and deep recesses, interlacing in arrangement, over the inner wall
      of the heart chambers. The compacted myocardium became thinning down gradually
      from the base to the apex of the heart. The non-compacted myocardium bundles
      locating close to the endocardium were coarse and orderless in arrangement,
      nuclei were irregular and abnormal, nevertheless, the arrangement and appearance
      of the muscle bundles near by the pericardium part were essentially normal and
      the cell nuclei were evenly distributed. CONCLUSION: There are no specific
      clinical manifestations obtained in patients with non-compaction of ventricular
      myocardium, however, the pathologic changes are characteristic and a clinical
      diagnosis can be made by using echocardiography.

PMID- 19575878
TI  - [Significance of high-risk human papillomavirus DNA in atypical squamous cells,
      cannot exclude high-grade squamous intraepithelial lesion].
AB  - OBJECTIVE: To explore significance of high-risk human papillomavirus (HR-HPV)
      testing in atypical squamous cells, cannot exclude high grade squamous
      intraepithelial lesion (ASC-H). METHODS: Presence of HR-HPV DNA was examined in
      45 patients with ASC-H using hybrid capture II (HC-II) test. Colposcopic
      examination and biopsy were taken all results were evaluated. RESULTS: Overall,
      33 of 45 (73.3%) ASC-H cases were biopsy proven cervical intraepithelial lesion
      (CIN). 36 of 45 ASC-H cases were HPV-DNA positive, including 19 cases of HSIL and
      over lesion; whereas no HSIL or over was found in 9 HR-HPV negative cases.
      Sensitivity and negativity predictive value of HR-HPV in ASC-H with HSIL and over
      lesion were both 100%. CONCLUSIONS: ASC-H strongly predicts the presence of HSIL,
      HR-HPV may serve as a predict select whether a patient with ASC-H should take
      colposcopic examination immediately, patients with positive HR-HPV should undergo
      immediate colposcopic examination, while negative HR-HPV is an excellent
      predictor of the absence of HSIL.

PMID- 19575879
TI  - [Influence of AKT on survival and apoptosis of gastric adenocarcinoma cells].

PMID- 19575880
TI  - [Study on DNA expression profiles in renal biopsies of patients with IgA
      nephropathy].

PMID- 19575881
TI  - [Soft tissue tumor of the back].

PMID- 19575882
TI  - [Calcifying fibrous tumor in gastric wall: report of a case].

PMID- 19575883
TI  - [Intraneural hemangioma of the median nerve: report of a case].

PMID- 19575884
TI  - [Clear cell papillary cystadenoma of left mesosalpinx associated with von Hippel
      Lindau disease: report of a case].

PMID- 19575885
TI  - [Primary squamous carcinoma of intestine: report of a case].

PMID- 19575886
TI  - [Diffuse capillary hemangiomatosis of spleen: report of a case].

PMID- 19575887
TI  - [Renal papillary adenoma in transplant donor kidney: report of a case].

PMID- 19575889
TI  - [Recent advances and applications of CXCR7].

PMID- 19575888
TI  - [Recent advances in DNA demethylation in tumor therapy].

PMID- 19575890
TI  - [Application of WHO classification and NCCN guidelines in diagnosis of lymphoma].

PMID- 19575891
TI  - [Advances in international classification of Epstein-Barr virus-associated
      lymphoproliferative diseases].

PMID- 19575892
TI  - [Expressions of CXCL13, CD10 and bcl-6 in angioimmunoblastic T-cell lymphoma and
      peripheral T-cell lymphoma, not otherwise specified].
AB  - OBJECTIVE: To study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic
      diagnosis of angioimmunoblastic T-cell lymphoma (AITL). METHODS: One hundred and
      fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise
      specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical
      hyperplasia (RH) encountered during the period from January, 1990 to January,
      2008 were retrieved from the archival files of the Department of Pathology, West
      China Hospital of Sichuan University, China. The morphologic features were
      reviewed and compared. Immunohistochemical study was performed by SP method for
      CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma
      gene rearrangement study was also carried out. RESULTS: Regressed follicles were
      evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3%
      (25/30) of RH cases, respectively. A marked increase of number of arborizing
      venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS
      cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with
      paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were
      restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed
      CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10
      and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115)
      of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular
      meshworks of CD21-positive follicular dendritic cells were found in all the AITL
      cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL
      cases. CONCLUSIONS: AITL is a type of lymphoma originated from the follicular
      helper T cells. Detailed morphologic assessment and use of immunohistochemical
      markers are essential for accurate diagnosis.

PMID- 19575893
TI  - [State of chromosome 3q27 and different subtypes of diffuse large B-cell lymphoma
      and their prognostic correlation].
AB  - OBJECTIVE: To study the immunophenotypic and genetic features of diffuse large B
      cell lymphomas (DLBCLs), and their relationship to prognosis. METHODS: Seventy
      three cases of DLBCLs with follow-up data were studied by using
      immunohistochemistry for CD3, CD10, CD20, bcl-6 and MUM-1. The DLBCLs were
      classified into germinal center B cell-like (GCB) and non-germinal center B cell
      like (non-GCB) subtypes according to Hans' algorithm. Fluorescence in-situ
      hybridization (FISH) for bcl-6 gene expression (located on chromosome 3q27) was
      performed on paraffin-embedded tissues of 54 cases. RESULTS: In the 73 cases
      studied, 16 cases (21.9%) belonged to GCB subtype and 57 cases (78.1%) belonged
      to non-GCB subtype. Breakage of 3q27 was detected in 11 of the 54 cases (20.4%)
      and proliferation was detected in 14 cases (25.9%). The five-year overall
      survival rate of GCB subtype was significantly higher than that of non-GCB
      subtype (78% versus 40%, P = 0.011). The bcl-6-positive cases had a better
      clinical outcome than that of the bcl-6-negative cases (P = 0.041). Breakage of
      3q27 predicted a worse overall survival. CONCLUSIONS: The current study shows
      that the prognosis of GCB subtype of DLBCLs is better than that of non-GCB
      subtype. The expression of bcl-6 protein predicts a better clinical outcome,
      while the breakage of 3q27 predicts a worse overall survival.

PMID- 19575895
TI  - [Clinicopathologic study of splenic marginal zone B-cell lymphoma].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnosis and differential
      diagnosis of splenic marginal zone B-cell lymphoma (SMZL). METHODS: The clinical
      data, histologic findings and immunophenotype of 8 SMZL cases were studied. IgH
      gene rearrangement was performed in 1 case. Follow-up information was available
      in 4 patients. RESULTS: The median age of the patients was 61.5 years (range: 36
      to 75 years). The male-to-female ratio was 1.7:1. All cases presented with
      massive splenomegaly. Five of six cases had abnormal blood counts: neutropenia
      and thrombocytopenia with two of them showing anemia. After splenectomy, the
      blood counts in 3/3 cases returned to normal levels. Post-operative fludarabine
      based chemotherapy was given to 3 patients, two of them achieved complete
      remission and 1 case died during the course of chemotherapy. The average survival
      time was 21.5 months (range: 6 to 60 months). Histologically, all of the 8 cases
      showed micronodular white pulp lesions. Six of them exhibited the classic
      biphasic appearance with central aggregates of small B cells rimmed by a
      peripheral zone of atypical monocytoid B cells. The remaining 2 cases had a
      monomorphous appearance, consisting mainly of atypical monocytoid B cells. There
      was infiltration of tumor cells in the red pulp, sheets in appearance in all 8
      cases. Immuno-histochemical staining showed CD20-positive (8/8), IgD-positive in
      2 of the 4 cases (2/4), CD5-positive in 1 of the 4 cases (1/4), 6 of the 6 cases
      were bcl-2-positive, cyclin D1-negative and bcl-6/CD10-negative, CD43-negative in
      5 of the 6 cases (5/6). The proliferation index, as highlighted by Ki-67
      immunostaining, was low (< 15%). CONCLUSIONS: SMZL is an indolent B-cell non
      Hodgkin lymphoma. The main clinical manifestations are splenomegaly and
      abnormalities in blood counts. The main modality of treatment is splenectomy.
      Adjuvant fludarabine-based chemotherapy helps to achieve complete remission. In
      general, the prognosis of this lymphoma type is good. The lymphoma cells
      predominantly grow in micronodular pattern, with atypical monocytoid B cells
      rimming around the small B cells, which aggregates in the center. The
      differential diagnosis includes other small B-cell lymphomas and lymphoid
      hyperplasia of spleen.

PMID- 19575894
TI  - [Extranodal nasal type NK/T-cell lymphoma: clinicopathologic and prognostic study
      of 55 cases].
AB  - OBJECTIVE: To study the clinicopathologic features and prognostic factors of
      extranodal nasal type NK/T-cell lymphoma (EN-NK/TCL) in Chinese patients.
      METHODS: Fifty-five cases of EN-NK/TCL diagnosed in Chinese patients during the
      period from 1998 to 2007 were studied by light microscopy, immunohistochemistry
      and in-situ hybridization. The follow-up information was analyzed. RESULTS: The
      male-to-female ratio was 1.89:1. The median age of the patients was 38 years. The
      commonest sites of involvement included nasal cavity and adjoining tissue
      (85.5%). Histologically, EN-NK/TCL was composed of small to medium-sized lymphoid
      cells. Angiocentric and angiodestructive growth patterns, coagulative tumor
      necrosis and apoptotic bodies were frequently observed. Immunohistochemical study
      showed that CD20, the B-cell marker, was negative in all cases. The positivity
      rates for T-cell markers CD3epsilon, CD4, CD5 and CD8 were 100% (49/49), 7%
      (3/46), 8% (4/48) and 63% (29/46), respectively. Most cases were also positive
      for NK-cell marker CD56 (79% 42/53). All cases expressed cytotoxic granule
      associated proteins TIA-1 and granzyme B. Only 17% (8/46) of the cases were
      positive for anti-apoptotic protein bcl-2. The proliferation index, as
      demonstrated by Ki-67 immunostain, varied: 30% (14/47) with a low Ki-67
      expression level (< or = 29%), 28% (13/47) with a medium level (30%-59%) and 42%
      with a high level (> or = 60%). There was a significant positive correlation
      between the bcl-2 positive expression and a high Ki-67 expression level. In-situ
      hybridization for EBV-encoded RNA was positive in all cases. Amongst the 41 cases
      with clinical information available, 63.4% presented with Ann Arbor stage I to
      II. The performance status score was 1 in 87.8% cases. High lactate dehydrogenase
      level was demonstrated in some patients (31.8%). Amongst the 27 cases with follow
      up data available, the median survival was 13 months. The overall 1-year, 2-year
      and 5-year survival rates were 52%, 31% and 20%, respectively. In general, cases
      with high proliferation index carried poor prognosis. CONCLUSIONS: EN-NK/TCL is a
      mature T-cell and NK-cell neoplasm which can be accurately diagnosed by
      histologic examination, immunohistochemical study and in-situ hybridization. The
      prognosis is usually not favorable. Proliferation index of the tumor represents
      an independent prognostic factor.

PMID- 19575896
TI  - [Clinicopathologic features of peripheral T-cell lymphoma, unspecified with
      follicular pattern].
AB  - OBJECTIVE: To study the clinicopathologic features of peripheral T-cell lymphoma,
      unspecified (PTL-U) with follicular pattern. METHODS: The clinical data,
      hematoxylin and eosin-stained sections of lymph node biopsies and follow-up data
      of 18 cases of PTL-U associated with follicular growth pattern were reviewed and
      studied. Eight cases of reactive lymphoid hyperplasia were used as controls. Semi
      quantitative observation by retiform micrometer rule was carried out.
      Immunohistochemical study was also performed in all cases. T-cell receptor and
      immunoglobulin heavy chain gene rearrangement studies were conducted by
      polymerase chain reaction-based method. RESULTS: The median age of the patients
      was 53 years. The male-to-female ratio was 1.57:1 in lymphoma group. All of the
      lymphoma patients presented with superficial lymphadenopathy, with (8/18) or
      without B symptoms. Histologically, the lymphoma was characterized by follicles
      of various sizes and shapes. The T zones were expanded by medium-sized lymphoma
      cells which contained clear cytoplasm and irregular nuclei. Mitotic figures were
      commonly identified. Immunohistochemical study confirmed that the lymphoma cells
      were of T-lineage. The proliferative index, as highlighted by Ki-67, was higher
      [average = (38.24 +/- 13.42)%/mm2] than that in the control group. T-cell
      receptor gene rearrangement was demonstrated in 71.4% (10/14) of the lymphoma
      cases. CONCLUSIONS: A definitive diagnosis of PTL-U with follicular pattern can
      be made on the basis of morphologic examination, immunohistochemical assessment
      and clinical features. Cases with atypical features can further be delineated by
      molecular analysis. Long-term follow up of these patients is prudent.

PMID- 19575898
TI  - [Application of BIOMED-2 primers in analysis of T-cell receptor gamma gene
      rearrangements in paraffin-embedded tissue specimens of T-cell lymphoma].
AB  - OBJECTIVE: To evaluate the practical values of PCR detectable T-cell receptor
      (TCR) gene rearrangement in paraffin embedded tissue samples in the diagnosis of
      T-cell malignancies using BIOMED-2 PCR multiplex tubes TCRgamma(A+B). METHODS:
      Traditional phenol-chloroform method was used to extract DNA from 55 cases of
      archival paraffin embedded tissues samples of T-cell malignancies and the DNA
      quality was evaluated by PCR-based amplification of housekeeping gene beta
      globin. The selected BIOMED-2 PCR multiplex tubes TCRgamma(A+B) were used to
      detect TCR gene rearrangement and comparison with the results of universal TCR
      primers (T(VG)/T(JX)) was performed. RESULTS: Positive detection rates by the
      BIOMED-2 multiplex tubes TCRgamma(A+B) and the universal primers (T(VG)/T(JX))
      were 76.4% and 60.0%, respectively. There were not statistical difference between
      the methods (P > 0.05). CONCLUSION: BIOMED-2 multiplex tubes TCRgamma(A+B) is
      suitable for detection of clonal rearrangements of TCR genes in current archival
      paraffin embedded tissue samples of T-cell malignancies.

PMID- 19575899
TI  - [Molecular confirmation of enterovirus type 71 infection: a post-mortem study of
      two cases].
AB  - OBJECTIVE: To investigate the diagnostic application of molecular detection of
      enterovirus type 71 (EV71) infection using post-mortem paraffin-embedded tissue.
      METHODS: Two autopsy cases of EV71 infection were studied by histopathological
      and immunohistochemical methods. Reverse transcription polymerase chain reaction
      (RT-PCR) was performed to detect the viral RNA in paraffin-embedded tissue
      samples. RESULTS: Characteristic features of acute encephalitis were seen in the
      brain, with most prominent lesions found in the brain stem in both cases.
      Inflammatory cells were largely CD68-positive microglia with a few CD15-positive
      neutrophils in the areas of neuronal necrosis. The 5'-untranslated region of EV71
      was detected in the medulla by RT-PCR using paraffin-embedded tissues of both
      cases. Sequencing analysis of the RT-PCR products showed 100% homology to the
      EV71 strain, recently submitted to the GenBank database from Fuyang, Anhui
      province. CONCLUSIONS: Molecular detection of EV71 can be performed on formalin
      fixed, paraffin-embedded tissue samples from fatally infected patients. Timely
      and accurate diagnosis of the infection by such molecular approach is crucial for
      the proper clinical and public health intervention.

PMID- 19575900
TI  - [Effect of KISS-1 on invasive potential and proliferation of esophageal squamous
      carcinoma cell line EC-1].
AB  - OBJECTIVE: To investigate the effect of KISS-1 expression on the potential of
      invasion and proliferation of esophageal squamous carcinoma cell EC-1. METHODS:
      Protein and mRNA expressions of KISS-1 were evaluated by Western blot and RT-PCR
      in four esophageal carcinoma cell lines (EC-1, Eca109, EC9706 and TE-1). Using
      liposome-mediated transfection, an eukaryotic expression vector (pcDNA3.1-KISS-1)
      of KISS-1 gene was transfected into EC-1 cells. Boyden chamber model, MTT and
      clone formation assay were used to detect the potential of invasion and
      proliferation. RESULTS: Western blot and RT-PCR showed a baseline low level of
      expression of KISS-1 protein (0.715 +/- 0.109) and mRNA (0.670 +/- 0.176) in EC-1
      cells. pcDNA3.1-KISS-1 expression vector was successfully transfected into EC-1
      cells. Western blot and RT-PCR showed that the expression of KISS-1 protein
      (1.143 +/- 0.218) and mRNA (0.877 +/- 0.162) in EC-1 cells transfected with
      pcDNA3.1-KISS-1 were significantly higher than those transfected with the control
      vector pcDNA3.1 (0.745 +/- 0.130, 0.685 +/- 0.128; t = 3.850, 2.481, P < 0.05)
      and the control cells (0.855 +/- 0.184, 0.677 +/- 0.138; t = 2.275, 2.306, P <
      0.05). Boyden chamber analysis showed that the invasiveness of the cells
      transfected with KISS-1 at 24 h (91.8 +/- 11.7), 48 h (117.8 +/- 11.1) and 72 h
      (139.2 +/- 11.8) were significantly reduced than that of the cells transfected
      with the control vector pcDNA3.1 (118.1 +/- 14.7, 141.7 +/- 13.2, 162.2 +/- 22.7;
      t = 3.153, 4.215, 3.569, P < 0.01) and the control cells (112.2 +/- 15.6, 138.1
      +/- 13.0, 162.3 +/- 14.0; t = 4.154, 3.797, 2.702, P < 0.05). MTT showed that the
      proliferation potential of cells after transfection with KISS-1 at 48 h (0.517 +/
      0.127) and 72 h (0.394 +/- 0.137) were significantly reduced than that of cells
      transfected with the control vector pcDNA3.1 (0.636 +/- 0.186, 0.513 +/- 0.150; t
      = 2.054, 2.709, P < 0.05) and the control cells (0.646 +/- 0.135, 0.511 +/-
      0.153; t = 2.276, 2.205, P < 0.05). Clone formation assay suggested that cells
      transfected with KISS-1 (157.2 +/- 36.4) showed significantly decreased clone
      formation than cells transfected with the control vector pcDNA3.1 (236.3 +/-
      78.1; t = 3.441, P < 0.01) and the control cells (242.5 +/- 48.6; t = 2.250, P <
      0.05). CONCLUSION: KISS-1 gene inhibits the potential of invasion and
      proliferation of EC-1 cells.

PMID- 19575901
TI  - [Overexpression of Tiam1 gene and its relationship with invasive and metastatic
      ability of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To explore biological aspects of Tiam1 gene expression in
      nasopharyngeal carcinoma cells. METHODS: Tiam1/C1199HA expression plasmids were
      transfected into nasopharyngeal carcinoma cells of C666-1 and CNE1 by
      lipofectamine2000. RT-PCR, real-time PCR and Western blot Analyses were performed
      to evaluate the expression of Tiam1 mRNA and protein levels, respectively. In
      vitro cell adhesion, wound healing and matrigel invasion assays were used to
      study the biological impact of Tiam1 on cell adhesion, mobility and invasion.
      RESULTS: Tiam1 over expression significantly increased the abilities of adhesion,
      migratory and invasion of C666-1 and CNE1 cells, comparing with that of the
      control untransfected cells (P < 0.05). CONCLUSION: Tiam1 expression correlates
      with the invasion and metastasis of nasopharyngeal carcinoma cells.

PMID- 19575902
TI  - [Expression of UCH-L3 in mouse hepatocarcinoma ascites cell lines Hca-F and Hca
      P].

PMID- 19575903
TI  - [Granulomatous slack skin: report of a case].

PMID- 19575904
TI  - [Carcinosarcoma of esophagus with malignant fibrous histiocytoma component:
      report of a case].

PMID- 19575905
TI  - [Goodpasture's syndrome: report of a case].

PMID- 19575906
TI  - [Value of immunohistochemistry in diagnosis and differential diagnosis of ovarian
      tumors].

PMID- 19575909
TI  - [To cognize retinitis pigmentosa with scientific view].
AB  - OBJECTIVE: Retinitis pigmentosa (RP) is the most common inherited eye disease
      that usually leads into blind, and is high simplex and clinical heterogeneity.
      Recent years, some new hereditary forms have been found, such as digenic RP,
      mitochondrial RP, incomplete dominant inheritance RP. The phenotype of RP is
      multiplicity. Incompatible phenomenon between genotype and phenotypes was shown
      in some genes such as peripherin/RDS, RHO, RP2 and RP3. The complicated phenotype
      was shown in the rare RP forms, such as centricity RP, stemma RP, retinitis
      pigmentosa sine pigmento, and retinal degeneration slow. Retinal transplantation,
      retinal implantation, drug and neurotrophic factor therapy, and gene therapy have
      been well studied worldwide and presented some hopeful efficacy. Ophthalmologists
      and practitioners should cognize the new advance and new knowledge on RP therapy
      with a scientific view for better serving the RP patients.

PMID- 19575910
TI  - [Paying attention to the research of apoptosis of retinal photoreceptor cells in
      retinal photochemical damage].
AB  - Many retinal degeneration diseases, such as retinitis pigmentosa and age-related
      macular degeneration, the main pathologic character of such retinal degeneration
      diseases is apoptosis of retinal photoreceptor cells. Recently, It is still short
      of effective treatment. Evidence from epidemiological studies and from
      experiments indicates that excessive light exposure may promote retinal
      degeneration, in which photoreceptor death by apoptosis leads to loss of vision.
      It is, therefore, of critical importance to pay more attention to further
      understanding of retinal photochemical damage and the apoptosis of retinal
      photoreceptor cells.

PMID- 19575911
TI  - [Expression of mouse telomerase reverse transcription in a mouse model of oxygen
      induced retinopathy].
AB  - OBJECTIVE: To establish oxygen-induced retinal neovascularization in mice and to
      detect the expression of mTERT in mice. METHODS: It was an experimental study
      Establishment of oxygen-induced retinal neovascularization in mice. Thirty-two 7
      day-old C57BL/6J mice were divided into oxygen-induced retinopathy group and
      control group without restriction of gender. In oxygen-induced retinopathy group,
      16 mice were exposed to 75% +/- 2% oxygen for 5 days and then to room air; In
      control group, 16 mice were raised in room air. Observation of the retinal
      neovascularization. On the postnatal day 19, The mice's vena caudalis were
      perfused with 2% Evens blue solution. Eyeballs were enucleated and fixed in 4%
      paraformaldehyde for half an hour. Then the retina was separated and flat-mounted
      on the slide. The morphologic changes of retinal vessel were observed and
      captured under fluorescence microscope. Histological observation and vascular
      endothelial cells counting. The eyeballs were enucleated and then fixed. After
      paraffin imbedding, 4 microm serial slices, hematoxylin-eosin staining, select
      one section every 60 microm to count the endothelial cell nucleus that break
      through the inner limiting membrane. Expression of mTERT mRNA were confirmed by
      reverse-transcription polymerase chain reaction (RT-PCR). In the each group, the
      retina were all carefully dissected on the postnatal day 19. The total RNA was
      isolated and cDNA was synthesized before RT-PCR was performed. The PCR products
      were separated by 2% agarose gel electrophoresis and photographed. Expression of
      mTERT mRNA were confirmed by Real-time PCR The total RNA was isolated and cDNA
      was synthesized (The same procedure as RT-PCR). Fluorescent real-time
      quantitative polymerase chain reaction system (total 20 microl) was made. The
      Fluorescent signals were detected at 60 degrees C. The expression of mTERT were
      confirmed by immunohistochemistry. At P19, 4 microm cross sections were made in
      the hyperoxia-exposed and normal retinas. Sections were incubated with rabbit
      anti-Human/Mouse/Rat Telomerase 60 minutes at 37 degrees C. Anti-rabbit
      immunoglobulin G, depending on the primary antibody, was used as a secondary
      antibody for 30 min. Peroxidase activity was detected with the substrate
      diaminobenzidine. Permanent slides were covered with a 1.5 mm thick cover slip,
      examined using a light microscope and photographed. RESULTS: The central retina
      was nonperfused region at P12. The most of the central retina showed almost no
      perfusion and the radial vessels appeared tortuous and dilated at P14. Retinal
      neovascularization occurred at maximum between postnatal day 17 and postnatal day
      19. Paraffin tissue slice with hematoxylin-eosin staining showed that in the
      control group the average counts of vascular endothelial cells which break
      through the inner limiting membrane were hardly seen, but in hyperoxia group were
      noticeably more than in the control group. Reverse-transcription polymerase chain
      reaction (RT-PCR) results: the mRNA of mTERT and bFGF in the retinopathy group
      were higher than in the control group (P < 0.05). Real-time PCR results: the
      expression of mTERT mRNA in the retinopathy group was noticeably higher than in
      the control group (F = 173.104, P < 0.05). Immunohistochemical staining showed
      that mTERT protein were positive in the retinal neovascularization of the
      hyperoxia group, but were negative in the retinal vessel of the control group.
      CONCLUSIONS: Telomerase reverse transcription and angiogenic correlation factors
      were up-regulated in a mouse model of oxygen-induced retinopathy, which may have
      therapeutic potential in the treatment with the neovascularization in
      retinopathy.

PMID- 19575912
TI  - [The expression of vascular endothelial growth factor of vitreous in patients
      with proliferative diabetic retinopathy].
AB  - OBJECTIVE: To explore the expression of vascular endothelial growth factor of
      vitreous in patients with proliferative diabetic retinopathy, and to analyze the
      relative factors. METHODS: It was a case-control study. Data of 50 eyes of 50 PDR
      patients who underwent vitrectomy were retrospectively analyzed. The vitreous
      fluid samples were obtained during surgery. The VEGF level in vitreous fluid was
      determined by enzyme linked immunosorbent assay, and the expression of vascular
      endothelial growth factor of vitreous in patients with proliferative diabetic
      retinopathy was analyzed. The mean follow-up was 9 months with a range from 6 to
      26 months. The VEGF levels in vitreous fluid were compared between PDR patients
      and normal control, and silicone oil tamponade group and without silicone oil
      tamponade group by t-test. The changes of VEGF levels in vitreous fluid in eyes
      with regression, stabilization, and progression were analyzed by analysis of
      variance. The effects of VEGF levels in vitreous fluid on PDR were analyzed by
      analysis of variance. RESULTS: The mean VEGF level of vitreous was (592.4801 +/-
      587.4267) ng/L in PDR patients, and it was (131.3022 +/- 26.9192) ng/L in normal
      control. VEGF level was significantly higher in PDR patients than that in normal
      control (t = 3.2315, P < 0.05). There were 10 eyes (20%) with progression of PDR,
      10 eyes (20%) with stabilization, and 30 eyes (60%) with regression. Vitreous
      level of VEGF was significantly higher in eyes with progression of PDR than that
      in eyes with stabilization or regression of PDR (q = -3.3187, -4.0843; P < 0.05).
      Vitreous level of VEGF was significantly higher in eyes without retinal
      photocoagulation than that in eyes underwent panretinal photocoagulation or local
      photocoagulation (q = -4.2187, -3.9672; P < 0.05). CONCLUSION: There is a
      correlation between the expression of VEGF of vitreous and the severity of PDR.
      The expression of VEGF of vitreous presents a relatively lower level in patients
      with stabilization and regression of PDR.

PMID- 19575913
TI  - [The effect of curcumin on DNA content, mitochondrial transmembrane potential and
      calcium of rabbit cultured retinal pigment epithelial cells].
AB  - OBJECTIVE: To investigate the Change of DNA content (apoptosis rate),
      mitochondrial transmembrane potential (DeltaPsim) and calcium (Ca(2+)) of rabbit
      retinal pigment epithelial (RPE) cells cultured with curcumin. METHODS: It was an
      experimental study. The RPE cells were dissociated from rabbit eyes and cultured.
      The RPE cells in the 4(th) passage were divided into 2 groups: curcumin group and
      control group (10% FBS-EMDM contains 0.05% dimethyl sulfoxide). The curcumin
      group contained 3 mass concentration: 10 mg/L, 15 mg/L and 20 mg/L. The MTT assay
      was used to evaluate the inhibition effect of RPE cells cultured with curcumin
      after 24 h, 48 h, 72 h and 96 h respectively. The IC(50) value in 24 h, 48 h, 72
      h and 96 h were gotten by Linear Regression. Flow cytometry was performed to
      detect the change of DNA content (apoptosis rate), DeltaPsim and Ca(2+) of RPE
      cells cultured with curcumin (15 mg/L) after 8 h, 24 h, 48 h and 72 h
      respectively. RESULTS: RPE cells were significantly inhibited by curcumin in a
      dose dependent and time dependent manner. The IC(50) value of curcumin at 24 h,
      48 h, 72 h and 96 h was 29.31 mg/L, 17.50 mg/L, 13.24 mg/L and 10.99 mg/L
      respectively. Ca(2+) was significantly increased at 8 h, 24 h, 48 h and 72 h
      after cultured with curcumin (15 mg/L) than that of the control group
      respectively (t = 7.50, 10.61, 20.74, 21.14, P < 0.01), and DeltaPsim was
      significantly decreased at 8 h, 24 h, 48 h and 72 h after cultured with curcumin
      (15 mg/L) than that of the control group respectively (t = 7.50, 11.74, 14.91,
      15.29, P < 0.01). There was no change of DNA content in RPE cells at 8h after
      cultured with curcumin (15 mg/L), but significantly lower than that of the
      control group at 24 h, 48 h and 72 h respectively (t = 10.00, 14.68, 13.68, P <
      0.01). CONCLUSION: The apoptosis of RPE cells induced by curcumin is caused by
      increase of Ca(2+) and decrease of DeltaPsim that causes decrease of DNA content.
      The RPE cells are significantly inhibited by curcumin, which may become a
      potential drug to prevent and treat proliferative vitreoretinopathy.

PMID- 19575914
TI  - [The remove of intraocular foreign body by the assistance of the injection of
      silicone oil].
AB  - OBJECTIVE: To evaluate the effect of the injection of silicone oil in helping the
      remove of intraocular foreign body throughout pars plana vitrectomy (PPV).
      METHODS: It was a series case study. This study included 17 eyes with intraocular
      foreign body from June 2007 to April 2008. Intraocular foreign bodies in these
      eyes were hardly removed, and all of the eyes had complicated and severe retinal
      injuries. The intraocular foreign bodies were taken out followed intravitreal
      injection of silicon oil. The retinal protective effects of silicon oil were
      studied. RESULTS: All the intraocular foreign bodies were removed successfully
      without any damage to the retina due to the viscosity of silicon oil and its
      gasket function. CONCLUSIONS: Intravitreal injection of silicon oil was able to
      help the removement of hardly-hold intraocular foreign body with PPV and avoid
      secondary retinal injury in this process.

PMID- 19575915
TI  - [Magnetic resonance imaging of the ocular motor nerves in normal volunteers].
AB  - OBJECTIVE: To display the detail functional anatomy of ocular motor nerves in the
      orbits, cavernous sinus and brainstem by high-resolution MRI. METHODS: Twenty
      normal subjects between 24 and 38 years of age, mean age was 28.25 +/- 4.07 (SD).
      Imaging of the ocular motor nerves at the brainstem was performed in 0.8 mm
      thickness image planes using 3D-FIESTA sequence; nerves in the cavernous sinus
      was imaged with a head coil, the FSE/T(1)WI was obtained in coronal planes;
      nerves to extraocular muscles (EOMs) in the orbits were imaged with FSE/T(1)WI
      oblique-coronal planes using surface coils, and within 2.0 mm thick planes. A
      human orbit was celloidin embedding and serially sectioned at 0.1 mm of thickness
      for HE stain, which would be used to distinguish motor nerves to the EOMs.
      RESULTS: Oculomotor nerves (CN3) and abducens (CN6) of the cisternal segment were
      well demonstrable in all normal subjects. Trochlear nerves (CN4) were depicted
      95%. CN3 could be demonstrated consistently in the cavernous sinus, because of
      their small diameter, CN4 and CN6 not always detectable. The larger inferior
      division of CN3 and branches to the target EOMs and CN6 were demonstrated well in
      all species. The superior division of CN3 was demonstrated 60%, CN4 was showed
      40%. CONCLUSION: 3D-FIESTA Sequence combined with MPR (Multiplanar Reformation)
      could precisely show the ocular motor nerves, as well as the relationships with
      adjacent structures in the cistern. The inferior division of CN3 and the CN6
      could be well depicted in the orbits. But of the small sizes and complicated
      neighboring structures in the orbit, the superior division of the CN3 and the CN4
      could not be demonstrated consistently. The capabilities of MRI can be fully used
      only with thorough knowledge of the complicated topographic relationships in the
      corresponding region.

PMID- 19575916
TI  - [Retrospective analysis of clinical characteristics of toxic anterior segment
      syndrome].
AB  - OBJECTIVE: To investigate the etiology, clinical features, treatment and
      prognosis of toxic anterior segment syndrome (TASS). METHODS: It was a
      retrospective series case study. The clinical data of eight definite diagnosed
      TASS cases were retrospectively analyzed. RESULTS: Among eight TASS cases, seven
      were post cataract surgery cases and one was post cornea penetrating injury.
      Three cases were caused by residual povidone iodine on instruments, 2 cases
      resulted from the misuse of distilled water as intraocular irrigating liquid
      during cataract surgery, 2 cases were produced by the countercurrent of
      antibiotic solution via the cornea-scleral incision into anterior chamber during
      subconjunctival injection at the end of the surgery, and 1 case was induced by
      the injection of the distilled water into the anterior chamber at the end of the
      surgery. Three TASS cases occurred during operation and 5 cases occurred at 1 day
      after operation. All eight cases suffered from the painless blurred vision. Three
      cases occurred during operation presented with decrease of corneal transparency
      and depigmentation of iris. On the first day after operation, all cases had
      diffuse corneal stroma edema and severe anterior uveitis. Dexamethasone 0.1% or
      prednisolone acetate 1% eye drops, three times per day or one time per hour was
      used in all cases. Carteolol 2% eye drop, two times per day, was used for the
      cases with ocular hypertension. The cornea was clear in 6 cases, but corneal
      endothelial decompensation in 2 cases after therapy. CONCLUSION: Various toxic
      agents injected into anterior chamber by misuse can result in TASS. All these
      misuse can be avoided. Early diagnosis and proper management may be important to
      improve the prognosis of TASS.

PMID- 19575917
TI  - [Clinical features and treatment of choroidal metastasis].
AB  - OBJECTIVE: To assess the clinical features and management of choroidal
      metastasis. METHODS: Fundus examination was performed in 49 patients (66 eyes)
      with choroidal metastasis. Fundus fluorescein angiography (FFA) was performed in
      44 cases, combined with indocyanine green angiography (ICGA) examination in 12
      cases. B-scan ultrasound examination was performed in 8 cases. Transpupillary
      thermotherapy (TTT) was performed in 24 eyes, combined with photo-dynamic therapy
      in one eye. Plaque radio-therapy was used in one eye. The parameters of treatment
      for TTT were 1.2 - 3 mm spot size, 450 - 1000 mV, 60 s; 2 sessions of TTT in 2
      eyes and 3 sessions in 3 eyes. RESULTS: Fourteen cases were male and 35 cases
      were female. Both eyes were affected in 17 cases (34.7%). Age ranged from 23 - 74
      years old with an average of 47 years. The visual acuity was 0.05 or less in 13
      eyes; 0.06 - 0.2 in 22 eyes and 0.3 or more in 31 eyes. Primary tumours were
      found in 40 cases (81.6%) (surgical excision in 25 cases), consisting of breast
      carcinoma in 16 cases (32.7%), lung carcinoma in 14 cases (28.6%), hepatoma and
      cholangiocarcinoma in 3 cases, colon and stomach carcinomas in 3 cases,
      gynecologic appendix carcinoma (including 1 case of ovarian mucous cyst
      adenocarcinoma) in 2 cases, nasopharyngeal adenocarcinoma in 1 case, vertebra
      tumor in 1 case, undetected in 5 cases (10.2%) and under detection in 4 cases
      (8.2%). The fundus had 1 lesion in 58 eyes (58/66 = 87.8%), 2 lesions in 4 eyes
      (4/66 = 6.0%), 3 or more lesions in 2 eyes (including 7 lesions in 1 eye).
      According to the location and development status of the lesions, they could be
      divided into solitary type, 39 eyes (39/66 = 59.1%); diffuse type, 19 eyes (19/66
      = 28.8%); and early type, 8 eyes (8/66 = 12.1%). FFA examination: early stage
      lesions showed hypofluorescence and later stage lesions showed moderate to strong
      hyperfluorescence. In 8 cases of solitary lesions, the size of the lesion
      measured by B-scan averaged 11.5 mm x 10.5 mm x 3.6 mm with the maximal height at
      4.9 mm. The tumor became flattened and vision remained stable at 3 months after
      plaque radiotherapy in 1 case. Three cases were followed-up for 2, 3, and 4
      months after TTT treatment. The lesions remained stable with vision unchanged or
      slightly decreased. CONCLUSIONS: The choroidal metastasis has specific clinical
      features. The classification of metastatic lesions into solitary, diffuse and
      early types is helpful for the evaluation of the disease process. The primary
      tumor can be found in 80% of cases. The most common primary cancer is breast
      carcinoma, followed by lung carcinoma. These two cancers account for 75% of
      primary tumors. In solitary type and early type lesions, TTT combines with
      systemic treatment could result in regression of lesions, saving of vision and
      improvement of the life quality.

PMID- 19575918
TI  - [Gene mapping and mutation detection in a family with congenital nuclear
      cataract].
AB  - OBJECTIVE: To map and detect the gene responsible for congenital nuclear cataract
      in a Chinese family. METHODS: Genomic DNA was extracted from the peripheral blood
      samples of members of the pedigree. Gene scan was performed using approximately
      400 microsatellite markers spaced at about 10 cM intervals (ABI). Linkage
      analysis was carried out using a Linkage software package. Additional
      microsatellite markers for the positive region were selected for precise
      targeting, and haplotype data were processed using Cyrillic software to define
      the region of the disease gene. Mutation detection was carried out by sequencing
      candidate genes. RESULTS: Suggestive evidence of linkage was detected at marker
      D2S325 (LOD score [Z] = 2.29, recombination fraction [theta] = 0.00). Precise
      targeting and haplotype analysis traced the disease gene to a 19.04 cM region
      bounded by D2S117 and D2S2382 on chromosome 2q32.3-q35. Direct sequencing of the
      candidate gene cluster revealed a G-->A transversion in exon 3 of CRYGC.
      CONCLUSIONS: The present study has identified a novel nonsense mutation in CRYGC
      associated with congenital nuclear cataracts in a Chinese family.

PMID- 19575919
TI  - [Comparison of contrast sensitivity and wavefront analysis after implantation of
      AcrySof IQ aspherical intraocular lens].
AB  - OBJECTIVE: To determine vision quality when testing two acrylic intraocular
      lenses, AcrySof IQ and AcrySof Natural, after routine cataract extraction and IOL
      implantation. METHOD: Prospective, randomized, double-masked study that 260 eyes
      of patients who underwent cataract extraction and IOL implantation was performed.
      Patients were randomly divided into 2 groups: AcrySof IQ or AcrySof Natural. One
      week, one and three month postoperative evaluations included contrast sensitivity
      and wavefront analysis. The independent-samples T test was used. P < 0.05 was
      considered statistically significant. RESULT: The AcrySof IQ group has
      significantly higher and middle spatial frequency of contrast sensitivity. The
      difference in low spatial frequency was getting significant along with time.
      Patients with AcrySof IQ had a reduction in total high-order aberrations and
      spherical aberration. There were no difference in coma between two groups.
      CONCLUSION: The use of aspheric acrylic AcrySof IQ IOL may improve the quality of
      vision as a result of the reduction of contrast sensitivity and spherical
      aberration.

PMID- 19575920
TI  - [The analysis of fundus fluorescein angiography, indocyanine green angiography
      and hemodynamics of retrobulbar blood vessels in central serous
      chorioretinopathy].
AB  - OBJECTIVE: To analyze the characteristics of the retrobulbar blood vessels'
      hemodynamics changes and the choroidal circulation disorder, and to observe the
      relations between retinal pigment epithelium's (RPE) pathological changes and
      them. METHODS: It was a case control study. For 57 (57 affected eyes and 57
      contralateral eyes) unilateral eye affected patients and 25 (50 eyes) normal
      health adults, we examined ophthalmic arteries (OA), posterior ciliary arteries
      (PCA) and short posterior ciliary arteries (SPCA) by color Doppler flow Imaging
      (CDFI), and recorded the peak systolic velocities (PSV), end diastolic velocities
      (EDV) and resistance indexes (RI) of them. We compared each hemodynamic parameter
      of the normal eyes with it of the affected eyes and contralateral eyes in
      patients group respectively, and contrasted them between affected eyes and
      contralateral eyes of the patients. Fundus fluorescein angiography (FFA) and
      indocyanine green angiography (ICGA) were performed simultaneously on 57 patients
      with Heidelberg retina angiography, and the images were analyzed in contrast. We
      used SPSS 12.0 statistics software was used in the study. To the PSV, EDV and RI
      of the OA, PCA and SPCA in affected eyes and contralateral eyes of the patients,
      we used paired t-test for the same sample to compare their hemodynamic
      parameters; to compare normal health adults' eyes with the affected eyes and the
      contralateral eyes of patients group respectively, we used two-group t-test. When
      the P-value was less than 0.05, there was a statistical significance. RESULTS:
      There was a more significant decrease of the hemodynamic parameters in both PSVs
      and EDVs of temporal PCAs (PSV: t = 3.044, P = 0.005; EDV: t = 3.731, P = 0.001)
      and temporal SPCAs (PSV: t = 2.822, P = 0.008; EDV: t = 3.194, P = 0.003)
      compared the patients group's affected eyes with normal health adults group eyes,
      there was a more significant decrease of them of temporal PCAs (PSV: t = 3.219, P
      = 0.003; EDV: t = 3.807, P = 0.001) and temporal SPCAs (PSV: t = 3.931, P =
      0.000, EDV: t = 3.145, P = 0.003) compared the patients group's contralateral
      eyes with normal health adults group eyes, and there was a statistical
      significance of them (P < 0.05). There was no difference in hemodynamic
      parameters of both PSVs and EDVs of temporal PCAs (PSV: t = 0.608, P = 0.548;
      EDV: t = 0.122, P = 0.904) and temporal SPCAs (PSV: t = 0.730, P = 0.470; EDV: t
      = 0.109, P = 0.914) between affected eyes and contralateral eyes of the patients,
      and there was no statistical significance of them (P > 0.05). The results of FFA
      and ICGA showed that all the RPE's leaks of 57 affected eyes appeared at the
      hypofluorescent regions of relative choroids; 52 cases of 57 affected eyes were
      followed by choroidal vessels dilatation at the early hypofluorescent regions,
      and appeared hyperfluorescence leakages in the late phase images; At the all
      regions of RPE's transmitted fluorescences of affected eyes and contralateral
      eyes, the corresponding choroids showed hyperfluorescence in the late phase
      images in ICGA; There were no RPE's transmitted fluorescences at the regions of
      20 affected eyes and 16 contralateral eyes in FFA, which showed
      hyperfluoresceince leakages in the late phase images of choroids in ICGA.
      CONCLUSIONS: CSC is possibly a bilateral disease associated with systemic
      pathologic conditions. Hypoperfusion and ischemia are the basal characteristics
      of retrobulbar blood vessels' circulation disorder and choroidal ultracirculation
      disorder. The damage of RPE is following to the choroidal circulation disorder.

PMID- 19575921
TI  - [Metabolism and detoxification of the lipid derived aldehyde, 4-Hydroxynonenal in
      diabetic cataractogenesis in rat].
AB  - OBJECTIVE: To study the metabolism of 4-hydroxynonenal (HNE), one of lipid
      derived aldehydes (LDAs), in diabetic rat lens and its role in diabetic cataract
      formation. METHODS: Experimental research. A factor design was used to set up the
      experiment statistically upon two factors: diabetic and normal control as
      treatment factors; day 30, 45 and 70 as the time factors. Normal and diabetic
      rats' lenses were incubated with HNE for 2 hours. HNE metabolites in the culture
      media were studied by high performance liquid chromatography (HPLC). Aldehyde
      dehydrogenase (ALDH) activity in normal and diabetic rat lens (30, 45 and 70 d
      after inducing of cataract) was detected by a spectrophotometer, ALDH protein and
      HNE-protein were detected by Western Blot. All data were analyzed by the
      Bonferroni test using SAS 8.0 software. RESULTS: The major pathway for HNE
      metabolism in normal lens was conjugation with glutathione (GSH) to form GS-HNE
      (45%), followed by HNE's oxidation to 4-hydroxy-2-nonenoic acid (HNA) by ALDH,
      which accounted for approximately 9.1% of HNE. The conjugation of HNE with GSH in
      diabetic lens was decreased approximately 64% at day 30 compared with the
      controls (F = 49.59, P < 0.001). The pathway of HNE oxidation by ALDH in the
      diabetic lens was enhanced approximately 1.7 times at day 70 compared to day 30
      (F = 11.51, P = 0.0442). A higher ALDH activity, greater amount of ALDH protein,
      and less amount of HNE-protein adduct were presented in diabetic rat lens.
      CONCLUSIONS: The pathway of conjugation of HNE with GSH is inhibited in diabetic
      lens which may play a role in the formation of diabetic cataract. The oxidation
      of HNE by ALDH is a compensation process for protecting the lens against diabetic
      damage.

PMID- 19575922
TI  - [Effect on the proliferation of bovine corneal endothelial cells by small hairpin
      RNA interference targeting p27Kip1].
AB  - OBJECTIVE: To clarify the proliferation of bovine corneal endothelial cells
      (bCEC) by interference with the recombinant plasmid of short hairpin RNA (shRNA)
      against p27Kip1, a kind of cyclin-dependent kinase inhibitor (CKI). METHODS: It
      was an experimental study. Three p27Kip1-shRNA template DNA sequences containing
      small hairpin structure were designed and synthesized as experimental groups.
      Plasmid expressing irrelevant shRNA with a random combination was used as
      negative shRNA. The products were inserted into the Pgensil-1 plasmid and the
      recombinant plasmid of Pgenesil-P1, Pgenesil-P2, Pgenesil-P3 and Pgenesil-HK were
      constructed. The recombinant plasmids were transfected into bCEC cells with
      liposome and a blank group. The expression of mRNA and protein of p27Kip1 was
      detected by RT-PCR and Western blot after stable transfection, and the plasmid
      with the best inhibitory effect was selected. The growth of the experimental
      group, Pgenesil-HK group and blank group were assessed by MTT. The influence of
      shRNA-p27Kip1 on bCEC cell cycle was deteceted by flow cytometry (FCM). All
      statistical analyses were performed using one-way ANOVA. RESULTS: Restrictive
      enzyme digestion and sequence analysis showed that four recombinant plamids were
      constructed successfully and the aim sequence was obtained. The expression of
      p27Kip1 mRNA and p27Kip1 protein of Pgenesil-P1 group, Pgenesil-P2 group and
      Pgenesil-P3 group were all lower than that in the control group, including blank
      group and negative siRNA group. The inhibitive rate of mRNA reached 32.71%,
      67.76% and 80.28% (F = 453.102, P = 0.000 in each group) and the inhibitive rate
      of protein reached 29.27%, 64.73% and 76.13% (F = 75.385, P = 0.000 in each
      group) compared with the blank group. As the lowest expression among the three
      positive shRNA group, Pgenesil-P3 was selected for the next steps. There was no
      significant difference between blank group and negative Pgenesil-HK of the
      expression of p27Kip1 protein (P = 0.356) and the express of p27Kip1 mRNA (P =
      0.246). Compared with the control group and the blank group, the growth of the
      bCEC transfected by Pgenesil-P3 was significantly promoted with increased cell
      percent of S-phrase (F = 334.957, P = 0.000) and decreased cell percent of G1
      phrase (F = 134.224, P = 0.000). CONCLUSIONS: shRNA-p27Kip1 can down-regulate the
      expression of bCEC effectively and increase the growth of bCEC. shRNA-p27Kip1 RNA
      interference may be an effective method to promote the proliferation of CEC.

PMID- 19575923
TI  - [Expression of matrix metalloproteinases and inhibitors on the scleral tissue of
      lamina cribrosa in rat with experimental chronic ocular hypertension].
AB  - OBJECTIVE: To investigate the expression of matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) in the sclera of lamina cribrosa
      in rat chronic elevated intraocular pressure (IOP) and its the relationship with
      the pathogenesis of glaucoma. METHODS: It was an experimental study. Chronic
      ocular hypertension (OHT) model was induced in the left eyes of 43 Wistar rats by
      cauterizing episcleral venous while the right eyes were used as control. The rats
      were divided into three groups: 13 for immunohistology, 15 for Western blotting,
      and 15 for RT-PCR by randomly computerized assignment and sacrificed at week 12
      after OHT induction. The expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the
      sclera lamina cribrosa was detected using immunohistology, Western blotting, and
      RT-PCR technique, respectively. Repeated measures ANOVA of two-factor Studies in
      SAS statistic software were used to analyze the data. RESULTS: After 12 weeks,
      compared with control eyes, the IOP of rat OHT eyes was significantly (F =
      1519.67, P < 0.01) elevated. The expression of MMP-2 and MMP-9 was increased in
      cell nucleus and cytoplasm in sclera lamina cribrosa in rat OHT when compared to
      control eyes with negative expression. No expressions of TIMP-1, TIMP-2 in sclera
      lamina cribrosa were found in both OHT and control eyes. The mean gray-scale
      values of MMP-2, MMP-9, TIMP-1, and TIMP-2 in OHT were significantly (F = 405.55,
      F = 436.11, F = 1167.77, and F = 4629.64, P < 0.01) higher than control eye by
      Western blotting (193.88 +/- 8.84 vs 117.38 +/- 10.76, 202.65 +/- 8.37 vs 134.13
      +/- 5.06, 283.63 +/- 5.65 vs 186.88 +/- 7.14, and 284.75 +/- 5.50 vs 183.0 +/-
      5.58), while by RT-PCR (200.50 +/- 3.25 vs 181.88 +/- 9.36, 200.13 +/- 2.95 vs
      181.75 +/- 5.85, 201.88 +/- 3.14 vs 179.25 +/- 9.21, and 195.50 +/- 3.55 vs
      179.75 +/- 7.12), respectively. CONCLUSION: The increased expression of MMP-2,
      MMP-9, TIMP-1, and TIMP-2 in lamina cribrosa in rat OHT eye indicates that MMPs
      and TIMPs may be involved in the pathogenesis of glaucoma.

PMID- 19575929
TI  - [A new change in studies of ophthalmology: translational medicine-from basic to
      clinic].
AB  - Translational medicine is a new concept in the field of international medicine
      that aims to reduce barriers and build relationships between clinical and basic
      research, and to translate scientific knowledge and research production into
      practical applications. Recently, the developments in the study of translational
      medicine in many fields have been reported abroad. However, the development of
      translational medicine is in the initial stage in China. A turning point will be
      brought to ophthalmic research by improving the development of translational
      research. This review introduces the concept and development of translational
      medicine as well as the recent advances in the studies of translational medicine
      in ophthalmology.

PMID- 19575930
TI  - [MicroRNA and progresses in the region of ophthalmology].
AB  - MicroRNAs (miRNAs) consist of a growing class of short non-coding RNAs (ncRNAs)
      that negatively regulate the expression of genes involved in development,
      differentiation, proliferation, apoptosis and other important cellular processes.
      They regulate gene expression at the post-transcriptional level by either
      degradation or translational repression of a target mRNA. Nowadays more than 400
      miRNAs have been identified in the human genome. A growing number of reports have
      established a link between a specific group of microRNAs and tissues in eyes,
      including cornea, len, retina. Here, we describe our current understanding of the
      structure, biogenesis and function of MicroRNAs, as well as their potential as
      novel therapeutic approaches in eye disease.

PMID- 19575931
TI  - [Updates on tissue engineering of the eye].
AB  - Tissue engineering has developed rapidly in the last 20 years and has shown a
      promising future in many aspects of ophthalmology, such as the ocular surface and
      the retina. But also it has been confronted with some major scientific problems.
      Tissue engineering conjunctiva and corneal epithelia have been clinically well
      applied in the reconstruction of the ocular surface; immortalizing corneal
      endothelia may be the key problem in creating tissue engineering cornea; and the
      future of tissue engineering retina may be not as good as that of artificial
      retina. This paper reviews current research and application in some major fields
      of ocular tissue engineering.

PMID- 19575932
TI  - [Correlation of IL-4 and IL-13 gene polymorphisms with asthma and total serum IgE
      levels].
AB  - OBJECTIVE: To investigate the correlation between the single nucleotide
      polymorphisms (SNP) of +33C/T in the promoter region of IL-4 gene and +1923C/T in
      intron-3 region of IL-13 gene and the susceptibility of asthma, and to study the
      impact of these polymorphisms upon total serum IgE levels. METHODS: The 2
      polymorphisms were determined by polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP), in 150 asthmatic subjects (asthma group)
      and 160 healthy controls (healthy control group) of the Han nationality in
      Shandong province enrolled from December 2003 to June 2007. The total serum IgE
      levels were determined by ELISA. RESULTS: The genotype frequencies of CC, CT and
      TT in +33C/T sites of IL-4 gene were 43% (68/160), 35% (56/160), 22% (36/160)
      respectively in the controls, and 18% (27/150), 36% (54/150), 46% (69/150)
      respectively in the asthmatic subjects. The genotype frequencies of CC, CT and TT
      in +1923C/T sites of IL-13 gene were 41% (66/160), 43% (68/160), 16% (26/160)
      respectively in the controls, and 21% (31/150), 38% (57/150), 41% (61/150)
      respectively in the asthmatic subjects. The distribution of genotype in each
      sites between the 2 groups was significantly different (chi(2) = 27.821, 26.544
      respectively, all P < 0.01). The CT and TT genotypes carried higher risks for
      asthma than CC genotypes (chi(2) = 21.870, 14.206 respectively, all P < 0.01).
      The total serum IgE levels of CC, CT and TT in +33C/T sites of IL-4 gene were (92
      +/- 37), (122 +/- 45), (146 +/- 44) KU/L respectively in the controls, and (179
      +/- 40), (294 +/- 51), (341 +/- 80) KU/L respectively in the asthmatic subjects.
      The total serum IgE levels of CC, CT and TT in +1923C/T sites of IL-13 gene were
      (85 +/- 31), (102 +/- 38), (144 +/- 49) KU/L respectively in the controls, and
      (186 +/- 65), (297 +/- 87), (363 +/- 140) KU/L respectively in the asthmatic
      subjects. In these 2 sites, the total serum IgE level of asthmatics was higher
      than that of the controls with the same genotype between the 2 groups (t = 4.653,
      6.547, 7.754; and 4.673, 6.784, 8.157 respectively, all P < 0.01). The total
      serum IgE levels of CT, TT genotypes were higher than CC genotypes in the same
      group (t = 5.748, 6.253 respectively, all P < 0.01). CONCLUSIONS: There was a
      significant correlation between the polymorphisms of +33C/T sites of IL-4 and
      +1923C/T sites of IL-13 gene and susceptibility to asthma and increase of the
      total serum IgE. The IL-4 gene and IL-13 gene may be important candidate genes
      for asthma.

PMID- 19575933
TI  - [Effects of matrine on airway inflammation and early airway remodeling in
      asthmatic mice].
AB  - OBJECTIVE: To observe the influence of matrine on airway inflammation and early
      airway remodeling in asthmatic mice. METHODS: Fifty BALB/c mice were randomly
      divided into 5 groups: a normal control group (A), an asthmatic group (B), a
      dexamethasone (DXM) group (C, 2 mg/kg), a high-dose matrine group (D, 50 mg/kg)
      and a low-dose matrine group (E, 25 mg/kg). The mice model of asthma in the B, C,
      D, and E groups was established by ovalbumin (OVA) intraperitoneal injections and
      aerosolization. Intra-gastric administration of different medications in C, D, E
      groups and 0.9% sodium chloride in B group were carried out 1 hour before
      provocation. 0.9% sodium chloride was used for intraperitoneal injection,
      aerosolization and intra-gastric administration in group A. The lung tissue
      slices were stained, and then the grade of inflammation around the wall of
      bronchi, mucous secretion, and the percentage of goblet-cells were counted. The
      areas of bronchial smooth muscle and of collagen deposition in airway wall were
      analyzed. The transcriptions and protein expressions of transforming growth
      factor-beta(1) (TGF-beta(1)) and connective tissue growth factor (CTGF) were
      measured respectively by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and immunohistochemistry. RESULTS: In the A, B, C, D, E groups, the grades of
      inflammation were 1.5 (1, 2), 4 (4, 5), 2 (1, 3), 2 (2, 3), 3 (2, 3.3),
      respectively; the degrees of mucous secretions were 1.5 (1, 2), 5 (4, 6), 2 (1,
      3), 2 (2.5, 4), 3 (3, 4), respectively. These airway inflammatory parameters in
      group B were significantly higher than in group A (chi(2) = 21.3, 22.6, P all <
      0.01), while they were remarkably decreased in group C compared to group B
      (chi(2) = 13.3, 15.0, P all < 0.01). These parameters in group D and group E were
      also lower than those in group B (chi(2) = 9.1, 10.9; 9.8, 9.7; P all < 0.05).
      The percentage of goblet cells in airway epithelium was (1.7 +/- 0.5)%, (54.7 +/-
      15.5)%, (20.4 +/- 5.9)%, (31.7 +/- 7.6)% and (36.2 +/- 10.8)%, respectively; it
      was significantly higher in group B than in group A (t = 12.0, P < 0.01), and
      remarkably lower in groups C and D than in group B (t = 7.7, 5.1, P all < 0.01),
      and lower in group E than in B group (t = 4.2, P < 0.05). In these 5 groups, the
      area of bronchial smooth muscle was (11.5 +/- 2.1) microm(2)/microm, (30.0 +/-
      3.3) microm(2)/microm, (15.2 +/- 3.1) microm(2)/microm, (22.2 +/- 4.8)
      microm(2)/microm and (26.5 +/- 3.4) microm(2)/microm, respectively; it was
      significantly higher in group B than in group A (t = 11.4, P < 0.01), and
      remarkably lower in groups C, D and E than in group B (t = 9.1, 4.7, 2.2, P all <
      0.01). The area of collagen deposition was (3.9 +/- 1.8) microm(2)/microm, (24.4
      +/- 6.1) microm(2)/microm, (15.4 +/- 3.5) microm(2)/microm, (16.6 +/- 6.0)
      microm(2)/microm and (17.5 +/- 4.4) microm(2)/microm, respectively; it was also
      significantly higher in group B than in group A (t = 9.3, P < 0.01), and
      remarkably lower in groups C and D than in group B (t = 4.1, 3.5, P all < 0.01),
      and lower in group E than in B group (t = 3.2, P < 0.05). The mRNA levels of TGF
      beta(1) were 160 +/- 25, 247 +/- 37, 174 +/- 23, 195 +/- 25 and 207 +/- 42,
      respectively, and those of CTGF were 86 +/- 8, 160 +/- 24, 94 +/- 10, 93 +/- 14
      and 104 +/- 10, respectively in the 5 groups. The levels were remarkably
      increased in group B, as compared to group A (t = 6.1, 11.6, P all < 0.01), and
      the levels in groups C, D and E were remarkably decreased, as compared to group
      B, the difference being significant (t = 3.7, 2.7, 5.1; 10.6, 8.6, 10.3; P all <
      0.01). The protein level of TGF-beta(1) in lung tissues was 21 +/- 5, 36 +/- 8,
      26 +/- 5, 26 +/- 5 and 26 +/- 5, respectively, and that of CTGF was 15 +/- 4, 27
      +/- 5, 21 +/- 4, 22 +/- 3 and 23 +/- 4, respectively in the 5 groups. The levels
      in B group were significantly increased, as compared to group A (t = 5.7, 6.4, P
      all < 0.01), and those in groups C and D were significantly decreased (t = 3.9,
      3.9; 3.2, 2.8, P all < 0.01), and that in group E was also lower (t = 3.8, 2.5, P
      all < 0.05), as compared to group B. In all the groups, the protein levels of TGF
      beta(1) and CTGF were positively correlated with the area of bronchial smooth
      muscle and with the area of collagen deposition (r = 0.435, 0.583, 0.522, 0.590,
      P all < 0.01). CONCLUSIONS: Matrine inhibited airway inflammation and early
      airway remodeling in asthmatic mice. The signal transduction of TGF-beta(1) and
      CTGF maybe involved.

PMID- 19575934
TI  - [Effects of leptin on airway inflammation and the expression of Th1/Th2 cytokines
      in asthmatic rats].
AB  - OBJECTIVE: To investigate the effects of leptin on airway inflammation and the
      expression of Th1/Th2 cytokines. METHODS: The obesity and acute asthma models
      were established in 40 female SD rats, which were randomly divided into a normal
      weight control group (group A), a normal weight asthmatic group (group B), a
      normal weight intervention group (group C), an obese control group (group D) and
      an obese asthmatic group (group E). The airway resistance and airway
      responsiveness were calculated by transpulmonary pressure and gas flow rate. The
      numbers of leukocytes, eosinophils (EOS) and neutrophils (N) in bronchoalveolar
      lavage fluid (BALF) were counted. The concentrations of interleukin-4 (IL-4),
      interferon-gamma (IFN-gamma) and leptin in serum and BALF were determined by
      ELISA. The protein and mRNA expression of leptin was measured by Western blot and
      RT-PCR respectively. RESULTS: The airway resistance in group C and E [(0.890 +/-
      0.106) cm H2Oxml(-1)xs(-1), (1.024 +/- 0.096) cm H2Oxml(-1)xs(-1), (1.129 +/-
      0.107) cm H2Oxml(-1)xs(-1), (0.946 +/- 0.104) cm H2Oxml(-1)xs(-1), (1.124 +/-
      0.095) cm H2Oxml(-1)xs(-1), (1.135 +/- 0.105) cm H2Oxml(-1)xs(-1), respectively.]
      was increased significantly compared to group B [(0.638 +/- 0.128) cm H2Oxml(
      1)xs(-1), (0.745 +/- 0.073) cm H2Oxml(-1)xs(-1), (0.773 +/- 0.090) cm H2Oxml(
      1)xs(-1)] (q = 7.128, 8.712, 8.318, 11.300, 11.258, 11.447, all P < 0.05). The
      numbers of leukocyte and neutrophils in group C and E [(91 +/- 9) x 10(4)/ml,
      (108 +/- 21) x 10(4)/ml, (12.4 +/- 4.0) x 10(4)/ml, (14.2 +/- 5.9) x 10(4)/ml,
      respectively.] were increased significantly compared to group B [(79 +/- 7) x
      10(4)/ml, (2.4 +/- 1.1) x 10(4)/ml] (q = 2.923, 7.063, 8.629, 10.182, all P <
      0.05). The concentrations of IFN-gamma were [(42.3 +/- 3.5) ng/L, (45.1 +/- 4.8)
      ng/L, (19.2 +/- 1.8) ng/L, (20.3 +/- 1.5) ng/L] in group C and E respectively,
      which were significantly higher than those of group B [(16.5 +/- 1.4) ng/L, (9.3
      +/- 1.0) ng/L] (q = 21.607, 23.952, 16.919, 18.799, all P < 0.05). The protein
      and mRNA expression of leptin in lung tissue in group C and E [(0.40 +/- 0.07)
      ng/L, (0.44 +/- 0.05) ng/L, (0.34 +/- 0.06) ng/L, (0.38 +/- 0.04) ng/L,
      respectively.] were remarkably higher than those of group B [(0.31 +/- 0.03)
      ng/L, (0.21 +/- 0.04) ng/L] (q = 4.648, 6.713, 8.222, 10.752, all P < 0.05).
      CONCLUSION: Leptin could aggravate airway inflammation featured by infiltration
      of neutrophils and enhancement of Th1 type inflammation.

PMID- 19575935
TI  - [Effects of leukotriene receptor antagonists on vascular endothelial growth
      factor and its receptors in a sensitized rat model].
AB  - OBJECTIVE: To investigate the effect of montelukast (MK) on airway inflammation
      and remodeling in asthmatic rats, and to explore the regulating role of MK on
      vascular endothelial growth factor (VEGF) and its receptors. METHODS: Twenty-four
      male Sprague-Dawley rats were randomly divided into 3 groups, a control group (n
      = 8), an asthmatic group (n = 8) and a MK treated group (n = 8). The rats were
      sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized
      ovalbumin. Airway reactivity of the animals were measured by animal lung function
      meter. VEGF levels and leukotriene D(4) (LTD(4)) in serum were measured by enzyme
      linked-immunosorbent assay (ELISA). The pathologic changes of bronchi and the
      lung tissue were evaluated, and the expression of VEGF and its acceptors was
      analyzed with immunohistochemistry. The vascular counts and vascular smooth
      muscle thickness were measured by using image analysis system. RESULTS: The
      bronchial provocation test showed that, in the asthmatic group, the average
      expiratory resistance increased remarkably. The serum levels of VEGF and LTD(4)
      in the asthmatic group were 31 +/- 6 and 11 +/- 4 respectively, significantly
      higher than those in the control group (17 +/- 5 and 6.1 +/- 0.7) respectively
      and in the MK group (15 +/- 4 and 9.8 +/- 1.6) respectively. (F 63.78, 39.56 all
      P < 0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR(1) and
      VEGFR(2) in the asthmatic group were increased, as compared to those in the
      control group and the treated group. The vascular counts were 14 +/- 2, 22 +/- 2
      and 16 +/- 4 in the control, the asthmatic, and the treated groups. CONCLUSIONS:
      VEGF and its receptors were over-expressed in the sensitized rat model, and
      involved in angiogenesis and airway remodeling. MK may be effective in reducing
      allergic airway inflammation and airway remodeling through VEGF and VEGFR.

PMID- 19575936
TI  - [The diagnostic value of quantitative measurement of a proliferation-inducing
      ligand mRNA in sputum samples from lung cancer patients].
AB  - OBJECTIVE: To establish a real-time fluorescence quantitative polymerase chain
      reaction (RFQ-PCR) method for quantifying a proliferation-inducing ligand (APRIL)
      mRNA in sputum samples from patients with non-small cell lung cancer (NSCLC), and
      to evaluate its role in the diagnosis of NSCLC. METHODS: Seventy-one cases of
      NSCLC and 62 cases of benign pulmonary disease were enrolled in this study from
      August 2007 to May 2008 in Affiliated Hospital of Nantong University, Jiangsu.
      Sixty-five healthy volunteers served as the control. The fluorescence of the PCR
      products was detected continuously during the amplification by RFQ-PCR. According
      to the standard curves created by plasmid DNA, the expression level of target
      genes in clinical samples was determined using software. The results were
      presented as the ratios of target genes to beta(2)-microglobulin (beta(2)-M)
      mRNA, and compared with those obtained by conventional cytological method.
      RESULTS: The detection range of the assay was from 38 copies/microl to 3.8 x
      10(6) copies/microl. The coefficients of variation values of both intra
      experimental and inter-experimental reproducibility were 8.5% and 13.6%,
      respectively. The expression of APRIL mRNA in tumor sputum was higher than that
      in benign pulmonary disease and healthy volunteers (t = 10.50, 11.32, P < 0.01).
      The positive rate for APRIL mRNA expression was 81.7% (58 of 71) in sputum
      samples of NSCLC, 3.2% (2/62) in benign pulmonary disease and 1.5% (1/65) in
      healthy volunteers when cut-off values for positivity were set at the x(-) +/- 2
      s of mRNA expression in health volunteers. The level of APRIL mRNA of NSCLC was
      not related to sex, age, smoking status, TNM stage and lymph node metastasis (P >
      0.05, respectively), but was related to pathology subtype and the location of
      tumors (P < 0.05, respectively). The APRIL mRNA assay (82%) produced a higher
      detection rate than conventional cytological method (14%) (chi(2) = 67.68, P <
      0.01). CONCLUSION: Measurement of the expression of APRIL mRNA in sputum by RFQ
      PCR showed high sensitivity and specificity, which maybe useful in diagnosing
      NSCLC.

PMID- 19575937
TI  - [Recombinant adeno-associated virus mediated RNA interference of angiogenin
      expression inhibits cell growth of human lung adenocarcinoma].
AB  - OBJECTIVE: To study the inhibition of angiogenin (ANG) expression in human lung
      squamous cancer cell strain-A549 through adeno-associated virus (AAV)-mediated
      RNA-interference, and therefore to observe its effect on the growth of cancer
      cells and tumor formation. METHODS: Recombinant AAV expressing H1-promoter
      induced small-interference- RNA (siRNA) targeting ANG (AAV-shANG) was
      constructed, and then transfected into A549 cells. A549 cells and cells
      transfected with AAV-Null were used as the control groups. The effects of the
      reduced expression of ANG by RNAi from AAV-shANG on the growth, formation,
      reproduction, apoptosis, and microvessel-density of the carcinoma were observed.
      RESULTS: In vitro experiment showed that AAV-shANG was constructed successfully,
      There was an significant decrease in the expression of ANG protein 72 h after
      transfection, compared with the normal A459 cells and AAV-Null cells (P < 0.01).
      Cell cycle analysis showed that the proliferation index (PI) of normal A549
      cells, AAV-Null cells and AAVshANG cells were 0.32 +/- 0.29, 0.35 +/- 0.38 and
      0.31 +/- 0.43, respectively. There was no statistic difference in the PIs among
      the 3 groups (P > 0.05). In vivo experiment using thymus-defect mice showed that,
      there was an remarkable reduction in the mass and volume of tumors in AAV-shANG
      transfected group, compared to the control groups. Microvessel-density was 9.4 +/
      1.5, 9.8 +/- 2.1 and 5.7 +/- 1.9, respectively in the 3 groups, a statistic
      difference among the AAV-shANG-transfected group, the normal A549 group and the
      AAV-Null transfected group. The percentages of apoptotic cells in each group were
      (7.7 +/- 3.1)%, (8.5 +/- 5.4)%, (17.1 +/- 8.6)%, respectively, the experimental
      group being higher than those of the control groups. Positive rates of PCNA were
      (84.8 +/- 9.7)%, (85.8 +/- 9.8)%, and (70.4 +/- 10.1)%, respectively, the AAV
      shANG transfected cancer cells showing a lower PCNA index than the control
      groups. CONCLUSION: AAV-mediated expression of siRNA could reduce the expression
      of ANG in cancer cells, significantly enough to inhibit cell proliferation,
      promote cell apoptosis and inhibit tumor growth.

PMID- 19575938
TI  - [Prevalence of obstructive sleep apnea-hypopnea syndrome in adults aged over 20
      years in Fuzhou city].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of obstructive sleep
      apnea-hypopnea syndrome (OSAHS) in adults aged over 20 years in Fuzhou city,
      there fore to provide epidemiological data for prevention and treatment of the
      disease, and establishing a data base for prospective study. METHODS: A total of
      5500 subjects were derived from a random and cluster sampling of the population
      in 5 districts of Fuzhou city. They were asked to answer the questions from a
      questionnaire at home. According to the degree of snoring, 315 subjects with a
      snoring score > or = 3 degree and 100 subjects with a snoring score = 2 degree
      were selected at random to undergo polysomnography for a whole night. The
      prevalence of the disease was estimated and the risk factors for OSAHS were
      analyzed. RESULTS: 4595 subjects (83.55%) responded, and validated questionnaires
      were obtained from 4286 subjects (effective power 93.28%); of whom 606 (14.14%)
      subjects had habitual snoring. The estimated prevalence of OSAHS defined by apnea
      hypopnea index (AHI) > or = 5 and Epworth sleepiness scale (ESS) > or = 9 was
      4.78%. Multivariate analysis revealed that age, smoking, family snoring, neck
      circumference, waist circumference, and abnormality of the upper airway were
      significant risk factors for OSAHS. CONCLUSIONS: The estimated prevalences of
      snoring and OSAHS in adults aged over 20 years in Fuzhou city was high.
      Strategies based on the epidemiological data in Fuzhou city are needed to cut
      down the prevalence and harm of OSAHS by controlling modifiable risk factors.

PMID- 19575939
TI  - [Study on changes of thrombi and vessel intima in a rat venous thromboembolism
      model].
AB  - OBJECTIVE: To observe the changes of thrombi and vessel intima in a rat model of
      venous thromboembolism (VTE). METHODS: Seventy-eight SD rats were randomly
      divided into deep vein thrombosis (DVT) group (n = 18), deep vein thrombosis
      pulmonary thromboembolism (DVT-PTE) group (n = 54) and control group (n = 6).
      Rats in DVT and DVT-PTE groups were undergoing local blocking of left femoral
      artery with micro vessel clip to cause DVT. One, 4, and 7 days later 6 rats from
      DVT group were killed with their femoral veins observed by light and electron
      microscopy. Rats in DVT-PTE group underwent injection of the thrombi from left
      femoral vein solution in normal saline into the right femoral vein 1, 4, and 7
      days after DVT formation to establish model of DVT-PTE. The 6 rats of each
      subgroup [D(n (1, 4, 7))P(n (1, 4, 7)) subgroups] were killed 1, 4, and 7 days
      after DVT-PTE formation respectively with their lungs observed by light and
      electron microscopy. RESULTS: (1) On day 1 after DVT, the successful rate of DVT
      was 100%. The positive thrombus rate in femoral veins on gross is lower on day 7
      after DVT [42% (10/24)] than that on day 1 after DVT (chi(2) = 19.765, P < 0.01).
      The successful rates of DVT-PTE model were 100% (18/18), 83% (15/18), 44% (8/18)
      in the D(1)P(n), D(4)P(n) and D(7)P(n) subgroups respectively. The successful
      rate of DVT-PTE model is lower in the D(7)P(n) subgroups than that in the
      D(1)P(n) (chi(2) = 13.846, P < 0.01) and D(4)P(n) (chi(2) = 5.900, P < 0.05)
      subgroups. (2) One, 4, and 7 days after DVT, there were reddish, mixed, and
      organized thrombi in femoral veins. The thrombi in pulmonary arteries caused by
      the 4 or 7 days thrombi of DVT showed lower dissolubility than that from one day
      thrombi of DVT. The positive thrombus rate in pulmonary arteries on gross is
      higher in the D(4)P(n) and D(7)P(n) subgroups [73% (11/15) and 100% (8/8)] than
      that in the D(1)P(n) subgroups [39% (7/18, chi(2) = 3.915, P < 0.05; chi(2) =
      8.474, P < 0.01)]. The ratio of vessel wall area and total vessel increased in
      D(1)P(7), D(4)P(4), D(7)P(4) and D(7)P(7) subgroups compared to the control group
      (P = 0.03, 0.00, 0.00, 0.011, respectively). (3) The junctures of femoral venous
      endothelial cells were ruptured and the intra-elastic layers were exposed on the
      1(st) day, then the endothelial cells and intra-elastic layers became to
      disappear on the 7(th) day. The hyperplasia of pulmonary arterial intimal were
      observed on the 4(th) or the 7(th) day after the thrombi in pulmonary arteries
      caused by the 1 or 4 days thrombi of DVT. However, pulmonary arterial endothelial
      cells and intra-elastic layers maybe disappear on the 1(st) day after the thrombi
      in pulmonary arteries caused by the 7 days thrombi of DVT. CONCLUSIONS: The age
      and nature of thrombi before the embolization are related to the outcome of
      emboli and pulmonary arterial intimal alterations. For intimal, there are the
      changes of hyperplasia, intra-elastic layers thickening and even disappearance in
      femoral veins and pulmonary arteries after VTE.

PMID- 19575940
TI  - [The research progress of fibroblast foci in idiopathic pulmonary fibrosis].

PMID- 19575957
TI  - [What else can we do for uveal melanoma].
AB  - Uveal melanoma (UM) is the most common intraocular malignant tumor in the adults.
      So far, known treatments have not been able to effectively improve the prognosis
      of the patients' life and the survival rate. Based on the above issues, it is
      imperative to think of what can we do for uveal melanoma. This paper reviews
      using local preservative therapy in combined treatment of UM, how to predict and
      evaluate the risk of metastasis, how to detect early metastasis, and whether or
      not systemic therapy to UM patients is necessary. We hope that through
      etiological study and through the evaluation of the effects of combined treatment
      of UM by large sample prospective control studies, we can find an effective
      therapy which can save the patients' eye and useful vision while simultaneously
      improving the prognosis, and ultimately, improving clinical diagnosis and
      treatment of UM in China.

PMID- 19575958
TI  - [Emphasis on pathology and hemodynamics based classification of orbital vascular
      lesions].
AB  - Orbital vascular lesions, mainly including hemangioma and vascular malformation,
      are the most common disorders among orbital diseases. Vascular lesions of the
      orbit have clinically complicated presentations and are very hard to deal with.
      Selection of therapeutic modality on orbital vascular lesions requires an
      appropriate classification of them. An improved classification of these lesions
      has been proposed by the Orbital Society based on the pathological types and
      hemodynamic features and has been extensively used in developed countries.
      However, orbital vascular lesions are still being classified based on morphology
      in China. This classification system does not represent the pathological
      difference between hemangioma and vascular malformation of the orbit, nor the
      hemodynamic characteristics among different vascular malformations of the orbit.
      Morphology based classification has hampered scientific dialogue and confused
      clinicians, with occasionally serious consequences for patients. Thus, the use of
      a pathology and hemodynamics based classification of orbital vascular lesions
      should be highly advocated. We can expect that the use of appropriate
      classification can improve the management of these lesions in our country.

PMID- 19575959
TI  - [Clinical manifestation and follow-up of melanocytoma of the optic disc].
AB  - OBJECTIVE: To investigate the clinical manifestation and follow-up of
      melanocytoma of the optic disc. METHODS: Retrospective case series study was
      taken to study the clinical data of the cases with melanocytoma of the optic disc
      at Peking Union Medical College Hospital from 1978 to 2007. The examination
      included direct and indirect ophthalmoscopy, fundus photography, fundus
      fluorescein angiography (FFA), fundus indocyanine green angiography (ICGA),
      optical coherence tomography (OCT) and B-scan. The clinical manifestation and the
      outcome in follow-up period were analyzed. RESULTS: Ten cases aged 31-58 years
      (mean 43 years) were included in this study. Among them, 9 cases were male, 1
      case was female. All cases were unilateral involved, 5 cases were right eye, 5
      cases were left eye. The distribution of the visual acuity was follows: light
      perception in 2 eyes, 20/200 in one eye, 20/20 or above in 7 eyes. The tumor mass
      at the optic disc with extensive serous detachment of retina was detected on B
      scan in one eye. The benign melanocytoma was diagnosed by vitreous fine needle
      biopsy for this eye. In other case, the tumor was found to be enlarged, visual
      field defect deteriorated, pigment granules appeared in the vitreous adjacent to
      the tumor during on year follow-up period. On the patient request, enucleation
      was performed to rule out the malignancy of the tumor. Pathologic study showed
      that the tumor cells were active, but benign state. The tumor size and visual
      acuity in other eight eyes remained stable in the follow-up period with one to 18
      years (mean 3.5 years). On FFA and ICGA, bilateral choroidal nevi were found in
      one eye. CONCLUSIONS: Melanocytoma of the optic disc is a benign tumor that
      rarely causes visual impairment. However, visual acuity may be impaired due to
      enlargement of the tumor or necrosis in tumor. It is important to follow-up every
      case with melanocytoma of the optic disc as long as possible.

PMID- 19575960
TI  - [Clinical characteristics of choroidal metastasis].
AB  - OBJECTIVE: To study the clinical characteristics of choroidal metastasis (CM) to
      promote the early diagnosis and differentiate from other choroidal tumors.
      METHODS: Retrospective clinical observational cases. All patients with choroidal
      metastasis underwent ophthalmologic examination including best corrected visual
      acuity (VA), slit-lamp examination, binocular indirect funduscopy, color
      photography, fundus fluorescein angiography (FFA), indocyanine-green angiography
      (ICGA), optical coherence tomography (OCT), A and B scan ultrasound examination,
      magnetic resonance image (MRI) as well as CT of the thorax, etc. RESULTS: Nine
      eyes of 5 patients with CM were examined. Unilateral choroidal involvement was
      present in 1 patient, bilateral in 4 cases. There were 1 case male and 4 case
      females. The age of these patients ranged from 31 to 56 years, median 45 years.
      Ocular symptoms included reduced vision in 4 patients and visual distortion in 1
      patient. Visual acuity was 20/400- < 20/63 in four eyes; 20/63- < 20/30 in two
      eyes and >or= 20/30 in three eyes. The primary cancer site was in the lung in 3
      patients, in the breast in 1 patient and in the stomach in 1 patient. Fundus
      characteristics: Typical CM was more often in the plateau-shaped than in the dome
      shaped; yellow-white or mottled in color and associated with subretinal fluid and
      retinal detachment. The tumor was found in the macular area and juxtapapillary
      area in 6 eyes, in the area between the macula and the equator in 3 eyes. CM was
      solitary in 5 eyes and showed multiple lesions in 4 eyes. By FA the lesions
      showed mottled hyperfluorescence in early stage and leakage in late stage. By
      ICGA the lesion showed blocked fluorescence and hypofluorescence. Choroidal mass
      showed moderate irregular internal reflectivity in A-scan ultrasound. B-scan
      showed a plateau-shaped solid mass. MRI examination of the lesion revealed
      moderate short T1W and T2W signals. The cancer antigen increased to 16.28 and
      4.95 microg/L in two cases. CA125 increased to 160.5 kU/L in one case.
      CONCLUSIONS: The choroid is the most common site for metastases. CM may precede
      the diagnosis of primary tumor. Evaluation of A, B scan ultrasound, CT of thorax
      and cancer antigen test may be important to exclude primary carcinoma from lung
      and breast in patients with yellow-white in color, plateau-shaped choroidal
      lesions, especially in both eyes, and without known metastatic diseases.

PMID- 19575961
TI  - [Analysis of treatment and prognosis of orbital adenoid cystic carcinoma].
AB  - OBJECTIVE: To summarize the treatment outcomes of orbital adenoid cystic
      carcinoma and to evaluate prognostic factors. METHOD: A retrospective case series
      study was performed on 75 patients with orbital adenoid cystic carcinoma treated
      from 1991 to 2006. RESULTS: The 2- and 5-year local recurrence rate of solid type
      orbital adenoid cystic carcinoma was significantly higher than that of the adeno
      tubiform type [2-year, 85% (17/20) vs 23.53% (8/34), chi(2) = 19.14, P = 0.000; 5
      year, 100% (19/19) vs 64.52% (20/31), Fisher's exact test, P = 0.003]. The
      regional extension and distant metastasis of solid type were more than those of
      adeno-tubiform type. The 5-year local recurrence rate treated by postoperative
      radiation was lower than that treated with only surgical excision [70% (14/20) vs
      92.86% (13/14); Fisher's exact test, P = 0.198]. The 5-year local recurrence rate
      in patients initially treated by orbital evisceration during the first time was
      lower than that of cases which evisceration procedure was used after the
      recurrence [25% (1/4) vs 75% (6/8), Fisher's exact test, P = 0.222]. Tumors may
      extend into intracalvarium, nasal cavity and temporal fossa. They may spread to
      the lung, bone, liver and lymph node. The 5-year metastasis rate was 25.71%
      (9/35). Both of the lung and bone metastasis rates were 33.33% (3/9). The overall
      5-year accumulative survival was 74.29% (26/35), mortality was 25.71% (9/35), and
      rate of survival without tumor recurrence was 37.14% (13/35). The 10-year disease
      free survival rate was 17.14% (6/35). Patients were most likely to die with
      intracranial extension. Surgical excision with postoperative radiation improved
      the 5-year survival rate to 80% (16/20). CONCLUSIONS: Orbital adenoid cystic
      carcinoma is one of the most malignant tumors in the orbit. They have a high
      local recurrence rate and survival rate. Tumor histological types and the
      treatment procedure can influence the prognosis. Combined therapy may decrease
      the recurrence and increase the survival rate.

PMID- 19575962
TI  - [Studies on multidrug resistance associated protein in retinoblastoma].
AB  - OBJECTIVE: To detect the expression of P-glycoprotein (P-gp), lung resistance
      associated protein (LRP) and multidrug resistance associated protein (MRP) in
      retinoblastoma (Rb), to analyze the relationship between the expression of
      multidrug resistant (MDR) markers with clinic-pathological factors, the
      correlations among these three markers, and to study the possible mechanism of
      multidrug resistance in Rb. METHODS: It was an experimental study. Seventy-five
      cases of Rb were studied with immunohistochemical methods using antibodies
      against P-gp, LRP and MRP. The relationship between their expression and the
      clinicopathological features of Rb, and the relationship between the expression
      of these three markers were investigated. RESULTS: The positive expression rates
      of P-gp, LRP and MRP were 64.0%, 25.3%, 36.0% in Rb, respectively. The co
      expression rates of P-gp and LRP, P-gp and MRP, LRP and MRP were 18.7%, 32.0%,
      20.0%, respectively. All tested proteins showed significant correlation to the
      differentiation of the tumor (P = 0.006, 0.000, 0.000, respectively), but no
      correlation was found between the expression of these markers and the age or sex
      of the patients. Significant positive correlations were observed between P-gp and
      MRP expression (P = 0.001), and between LRP and MRP expression (P = 0.000).
      CONCLUSIONS: The intrinsic multidrug resistance of Rb involves the combined
      effects of P-gp, LRP and MRP.

PMID- 19575963
TI  - [Relationship between vasculogenic mimicry and clinical pathological characters
      in retinoblastoma].
AB  - OBJECTIVE: To explore if vasculogenic mimicry (VM) exists in retinoblastoma (Rb)
      and to explore the clinical significance of VM. METHODS: It was an experimental
      study. Sixty Rb specimens with complete clinical and prognostic data were
      collected. Periodic acid-Schif staining and immunohistochemical staining of CD34
      were conducted to explore if VM exists in those Rb specimens. The expression of
      HIF-1alpha and VEGF were examined by immunohistochemical staining. The expression
      of CD34 endothelial antigen was used to label the neo-microvessels. Microvessel
      density (MVD) in retinoblastoma tissues was calculated. RESULTS: In HE staining
      slides, VM was present in Rb specimens and was formed by tumor cells but not
      endothelial cells. Red blood cells were present in the VM. VM existed in 18.33%
      (11/60) of the Rb specimens. Low R-E graded Rb specimens exhibited a higher VM
      positive rate than that in the high R-E graded Rb (chi(2) = 8.861, P < 0.05). The
      positive rate of VM was 4.34% in differentiated type of Rb and was 22.02% in
      undifferentiated type of Rb (chi(2) = 4.872, P < 0.05). HIF-1alpha and VEGF
      expressions in Rb with VM were significantly greater than those in Rb without VM
      (P = 0.001). The density of endothelial vessels correlated with VM. The mean MVD
      was 49.77 +/- 2.05 in Rb without VM and 36.53 +/- 1.15 in Rb with VM (P < 0.05).
      CONCLUSIONS: VM exists in Rb. Highly differentiated Rb exhibits more VM than that
      in less differentiated Rb. Expression of HIF-1alpha and VEGF is greater in Rb
      with VM, indicating that these factors may stimulate the occurrence of VM.

PMID- 19575964
TI  - [Development of stereopsis among children].
AB  - OBJECTIVE: To study the development of stereopsis in children from 30 to 50
      months of age. METHODS: It was a prospective study.We examined the visual acuity
      and stereopsis of 152 normal children from 30 to 50 months of age. The stereopsis
      was examined with Titmus, RPS and TNO. RESULTS: In 152 children, a complete
      examination was performed in 119 children had visual acuity of >or= 0.6; 12
      children had visual acuity of < 0.6; 21 children could not complete the
      examination. The mean age of these 21 children was significantly lower than the
      others. Using Titmus 60'', Titmus 100'' and RPS 60'' as the normal criteria, the
      normal ratio of near stereopsis acuity in the 119 children was correlated to the
      age by chi(2) test. They were divided into four groups by 5 month-age groups. The
      normal ratio in the 46 to 50 month group was significantly greater than that in
      the other three groups. The normal ratios was 89.9%, 94.1% and 95.0% for the
      criteria of Titmus 100'', RPS 200'' and TNO 240'', respectively. CONCLUSIONS: The
      stereopsis in children from 30 to 50 months of age is still in developing status.
      We suggest using 100'' for Titmus, 200'' for RPS and 240'' for TNO as normal
      stereopsis criteria in 3 to 4 year old children. RPS provides a reliable
      procedure for the measurement of stereopsis acuity in preschool children.

PMID- 19575965
TI  - [Clinical research of accommodating intraocular lens].
AB  - OBJECTIVE: To assess the visual outcomes and accommodative amplitude of
      accommodating intraocular lens (AIOL). METHODS: Case control study. Thirty eyes
      of 22 patients with cataracts had undergone phacoemulsification and implantation
      of AIOL. Twenty nine eyes of 22 age- and sex-matched patients with cataracts had
      the same surgery but foldable acrylic IOL were used as the controls. All patients
      were assessed for accommodation amplitude, visual acuity and for change of
      anterior chamber depth (ACD) at 6 and 12 months after surgery. Accommodation
      amplitude was measured using the pushing-up test. The change of ACD was measured
      with OCULUS Pentacam analysis system. RESULTS: During the follow-up time, the
      patients in the test group had better uncorrected near vision acuity (UCNV) and
      distance corrected near vision acuity (DCNVA)(P = 0.000). The test group had the
      same corrected vision acuity as the control group. Six months after surgery, push
      up test showed that the mean accommodative amplitude was (1.60 +/- 0.57) D in the
      test group and (1.10 +/- 0.70) D in the control group. The change of the ACD was
      (0.50 +/- 0.37) mm in the test group and (0.08 +/- 0.06) mm in the control group.
      Twelve months after surgery, push-up test showed that the mean accommodative
      amplitude was (1.38 +/- 0.52) D in the test group and (1.06 +/- 0.61) D in the
      control group. The change of the ACD was (0.30 +/- 0.27) mm in the test group and
      (0.10 +/- 0.09) mm in the control group. CONCLUSIONS: In the present study, the
      Tetraflex AIOL showed greater accommodative amplitude and better near visual
      acuity than those of the control group with conventional IOL. But 6 months later,
      all of these measurements in the test group were decreased.

PMID- 19575966
TI  - [Agreement measurement of ocular wavefront aberrations with three different
      aberrometers].
AB  - OBJECTIVE: To assess the repeatability and difference of ocular wavefront
      aberrations measured with ray-tracing, dynamic skiascopy, and Hartmann-Shack
      aberrometers. METHODS: It was an agreement study. Ocular aberrations data
      obtained by using iTrace (Tracey Technologies), OPD SCAN (Nidek) and WASCA
      (Zeiss) wavefront aberrometers were analyzed. Eighty six eyes of 45 patients were
      measured three times. The difference between the measurement and the mean of
      three consecutive measurements were analyzed to verify the reproducibility. The
      difference in sphere, cylinder, spherical equivalent (SEQ) and high order
      aberration (HOA) errors obtained from different aberrometers were evaluated.
      RESULTS: Repeatability errors of these three wavefront analyzer were found to be
      low. Comparisons on the same eye showed that there was a significant difference
      (P < 0.01) in sphere and cylinder between ray-tracing aberrometer and the others
      in high SEQ group (>or= -6.00 diopter). For HOA, all aberrometers obtained
      similar results in low SEQ group (< -6.00 diopter). In the high SEQ group, the
      ray-tracing aberrometer showed statistically higher data in HOA and coma (P <
      0.01), and there was no significant difference between the skiascopy and the
      Hartmann-Shack aberrometer. The iTrace-OPD and iTrace-WASCA HOA difference
      correlated with spherical equivalent in the high SEQ group (r = -0.418, -0.399, P
      < 0.01). CONCLUSION: All devices produced similar results of reproducibility, but
      showed varying results in the ocular total wavefront reading.

PMID- 19575967
TI  - [Clinical observation of trabeculectomy for primary angle closure glaucoma].
AB  - OBJECTIVE: To evaluate the effect of trabeculectomy on intraocular pressure (IOP)
      and complications in eyes with primary angle closure glaucoma (PACG). METHODS: It
      was retrospective clinical study. PACG was classified as acute primary angle
      closure glaucoma (APACG) group and chronic primary angle closure glaucoma (CPACG)
      group. APACG was then divided into acute attack phase and chronic phase, and
      CPACG was divided into chronic phase and late phase. IOP, best corrected visual
      acuity were compared before and after trabeculectomy in different subgroup of
      PACG. In addition, the incidence of complications of trabeculectomy was assessed.
      Statistical analyses were performed using SPSS 12.0 statistics software.
      Categorical variables such as best corrected visual acuity were compared using
      nonparametric test, continuous variables such as age and IOP were compared
      between the two groups using independent two-sample t-tests. Pre- and
      postoperative IOP were compared using one-way analysis of variance of repeated
      measures. RESULTS: 40 eyes (37 cases) of APACG and 56 eyes (45 cases) of CPACG
      were enrolled in this study. The median follow-up period was 24 and 25 months,
      respectively. IOP was significantly decreased from (53.6 +/- 17.9) mm Hg (1 mm Hg
      = 0.133 kPa, preoperation) to (10.5 +/- 4.9) mm Hg (postoperation) at time of
      discharging from hospital and (14.0 +/- 10.3) mm Hg at time of final follow up in
      APACG (F = 100.783, P < 0.01), respectively, and from (36.8 +/- 13.8) mm Hg to
      (11.7 +/- 4.2) mm Hg at time of discharging from hospital and (13.8 +/- 4.5) mm
      Hg at time of final follow up in CPACG (F = 54.383, P < 0.01), respectively. The
      IOP remained controlled (< or = 21 mm Hg) without antiglaucomatous medication in
      38 eyes (95.0%) of APACG and in 50 eyes (89.3%) of CPACG. Visual acuity was
      significantly (H = 12.316, P < 0.01) decreased after trabeculectomy in all sub
      types of PACG by Kruskal-wallis analysis. Shallow anterior chamber was commonly
      occurred after trabeculectomy. CONCLUSIONS: Trabeculectomy is an effective method
      to control IOP in APACG and CPACG. However, the high proportion of impaired
      vision was found following trabeculectomy in this study and warranted further
      clinical investigation.

PMID- 19575968
TI  - [Normal human bulbar conjunctiva on confocal microscopy in vivo].
AB  - OBJECTIVE: To analyze the morphology of human bulbar conjunctiva by in vivo laser
      scanning confocal microscopy. METHODS: This research was a cross-sectional study.
      From February to July 2008, 50 eyes of 50 healthy subjects were enrolled in this
      study. They had no history of ocular trauma, infection or contact lens wear and
      had no found after routine slit-lamp examinations. In vivo laser scanning
      confocal microscopic examinations were performed on the superior, inferior, nasal
      and temporal bulbar conjunctiva and the images were recorded. The morphology of
      bulbar conjunctiva was analyzed and the density of epithelial cells, dendritic
      cells and goblet cells were calculated. One-way analysis of variance (ANOVA) was
      used to compare the means of epithelial cell densities in different layers and
      goblet cell densities in different positions. Subsequently the datum between two
      groups were analyzed by least significant difference (LSD). RESULTS: Superficial
      epithelial cells of bulbar conjunctiva were characterized as large loose-arranged
      cells with a hyporeflective nucleus. The mean density is (1643 +/- 206)
      cells/mm(2). Intermediate epithelial cells were captured with features of oval
      small tight-arranged cells with a punctiform hyperreflective nucleus. The mean
      density is (4693 +/- 228) cells/mm(2). Basal epithelial cells appeared to be
      polygonal and regular-arranged within hyperreflective cell borders. The mean
      density is (4420 +/- 230) cells/mm(2). There was a significant difference among
      three kinds of conjunctival epithelium (F = 1160.312, P = 0.000). The presumed
      goblet cell was defined as a large hyperreflective oval-shaped cell with
      relatively homogeneous brightness, crowded in groups or mainly dispersed. The
      mean density is (432 +/- 72) cells/mm(2). The dendritic cell appeared to be
      hyperreflective corpuscular particles with dendritic processes scattered among
      conjunctival epithelial cells. The mean density is (22 +/- 25) cells/mm(2). The
      basement membrane, a prominent hyperreflective band, separated epithelial cells
      from subepithelial structure. Bulbar conjunctival substantia propria, beneath the
      basement membrane, was mainly composed of highly vascularized, loose connective
      tissues which were irregularly arranged fibers or a network of fibers, punctiform
      hyperreflective immune cells and sharp flows of blood vessels. CONCLUSION: In
      vivo laser scanning confocal microscopy is a useful tool in the analysis of the
      bulbar conjunctival morphology, which provided a fast and noninvasive method for
      the diagnosis of ocular surface diseases.

PMID- 19575969
TI  - [Prevention of mouse corneal allograft rejection by micromolecular compound J2].
AB  - OBJECTIVE: To investigate the effects of J2 on the prevention of corneal
      allograft rejection in mice. METHODS: Randomized control design was applied. One
      hundred C57BL/6 and thirty eight BALB/c mice were used as donors and recipients,
      respectively, to establish a corneal allograft model. These mice were randomly
      divided into A, B, C and D groups. There were 25 mice in each group. Group A,
      autograft control; Group B, allograft control (placebo was used in this group);
      Group C, allograft and treated with intraperitoneal ciclosporin A (CsA, 10 mg *
      kg(-1) * d(-1)) and Group D, allograft and treated with intraperitoneal J2 (15 mg
      * kg(-1) * d(-1)). All medications were applied on the day of transplantation and
      were continuously administrated for 12 days. Graft survival index, paraffin
      sections with HE staining and immunohistochemical staining of frozen sections
      were observed in each group 1, 2, 3 and 4 weeks after operation. IL-2 and IL-10
      expression of cornea was detected by RT-PCR. One-Way ANOVO analysis was used to
      compare transplant survival time of the corneal allograft of each group. RESULTS:
      The average transplant survival time in the corneal allograft controls was (18.88
      +/- 4.19) d. Treatment with J2 resulted in a significant increase of grafts'
      survival time (33.62 +/- 6.80) d (q = 0.85, P < 0.01). There was no significant
      difference between J2 and CsA groups. Histological examination showed that
      numerous lymphocytes infiltrated into the grafts 21 days after the operation in
      the control groups. Mild lymphocytes infiltration was found in both CsA and J2
      groups. Immunohistochemical studies showed that large amount of CD4(+) and CD8(+)
      T-lymphocytes infiltrated into the grafts of the placebo group at 21 days. J2 and
      CsA groups only showed a small number of CD4(+) and CD8(+) T-lymphocytes in the
      grafts. RT-PCR showed that few IL-2 and IL-10 genes were expressed in the
      autologous transplantation group in the first week, and the expression of these
      two cytokines showed no significant increase during following three weeks. Both
      genes were expressed from the first week in the allogeneic transplantation group
      and significantly increased in the third week. Both genes were expressed from the
      first week in CsA and J2 group, expression was reduced in the second and third
      weeks. Expression of these cytokines in the fourth week was stronger than those
      in previous three weeks. CONCLUSION: J2 can inhibit corneal rejection in
      allograft mice model and its effect is similar to that of CsA.

PMID- 19575970
TI  - [Expression of CD11b in the retinal microglia in chronic hypertension rat].
AB  - OBJECTIVE: To study the expression of CD11b in the retinal microglia in laser
      induced ocular hypertension (OHT) SD rat. METHODS: It was an experimental study.
      OHT was induced by the coagulation of trabecular meshwork using 532-laser in
      sixty SD rats. Intraocular pressure (IOP) was measured by Tonopen-XL, the
      expression of CD11b in retinal microglia detected by immunohistochemistry, and
      retinal ganglion cells (RGCs) were labeled with Dextran Tetramethyl Rhodamine
      (DTR) and counted by Image-Pro Plus Version 6.0 image analysis software at 2
      weeks, 1, 2, 3, 4, 5, and 6 months, respectively. All the numerical data were
      statistically analyzed by SPSS 13.0 software. RESULTS: Although the IOP of
      experimental groups are still the similar level at 2w after coagulation (t =
      1.124, P = 0.287), Compared to control eyes, IOP in lasered eyes was
      significantly (t = 2.487, P = 0.036) increased at 1 month, lasting for 3 months
      and returned to normal from 5 to 6 months (t = 1.103, P = 0.290). The expression
      of CD11b in the retinal microglia in the lasered eyes was significantly more
      intensive than that in control eyes at 1 month (t = 3.333, P = 0.008) and faded
      after 5 months, a similar pattern to IOP response, that two group data shows
      significant dependability (r = 0.891, P = 0.014). The number of RGC was
      significantly reduced from 1 month to 6 months (t = 3.316, P = 0.009), the
      velocity of reducing seems dependability to the advancing of IOP (r = 0.757, P =
      0.021). CONCLUSIONS: The expression of CD11b in retinal microglia is fluctuated
      with chronic OHT pattern and RGCs injury level indicating that the injury
      antigens by microglia are presented in the retina with the increase of IOP and
      activate the immunologic process leading to glaucomatous RGCs damage. It suggests
      that it is important to effectively control the IOP in order to reduce the risk
      of immune induced retinal damage by microglia.

PMID- 19575971
TI  - [Analysis of the academic level and impact of ophthalmological periodicals in
      China].
AB  - OBJECTIVE: To analyse the whole level and impact of ophthalmological periodicals
      in China. METHODS: It was studied by using bibliometrics analysis method.
      According to the data of CAJCCR in 2002 to 2007 and Chinese Citation Database in
      2001 to 2007. The impact factor (IF), non-self-citing impact factor, total cited
      frequency, cited articles, immediacy index, rate of fund papers, web immediacy
      download rate, average value of h index were analysed and the non-self-citing
      rate, h(2)/n, high cited articles were calculated. In addition, the results of
      cited by cole databases at home and abroad. RESULTS: The average value of IF and
      cited frequency of 13 kinds of ophthalmological periodicals were 0.3940 and 657
      respectively in 2001 to 2006, which were higher than that of D part of CAJCCR.
      The periodicals which the five indexes of IF, non-self-citing impact factor,
      total cited frequency, the non-self-citing rate, immediacy index, rate of fund
      papers, web immediacy download rate, average value of h index and h(2)/n, high
      cited articles were Top 5 and cited by five or more than five kinds of the cole
      databases at home and abroad were Chinese Journal of Ophthalmology, Chinese
      Journal of Ocular Fundus Diseases, Practical Chinese Journal of Ophthalmology and
      Chinese Journal of Optometry & Ophthalmology. Most of indexes of Chinese Journal
      of Ophthalmology were the first. CONCLUSIONS: There are big difference between
      the 13 kinds of ophthalmological periodicals. The qualities of some
      ophthalmological periodicals should be improved.

PMID- 19575977
TI  - [Risk factors and the progress of primary open-angle glaucoma].
AB  - The risk factors related to the progress of glaucoma have been investigated and
      revealed the involvement of the systemic factors and ocular factors that include
      intraocular pressure (IOP) and non-IOP factors. Multi-center randomized studies
      have demonstrated that IOP is an important risk factor in the development of
      ocular hypertension (OHT) to the onset of POAG or POAG progress. These large
      scale randomized clinical trials indicate that the only effective way to delay
      the deterioration of progressive optic neuropathy is to low IOP. Establishing a
      target IOP, reducing IOP, and especially controlling nocturnal IOP fluctuation
      are important measures for the prevention of glaucoma progress. While non-IOP
      risk factors come from age, central corneal thickness (CCT), duration of optic
      disc hemorrhage, the degree of severity of glaucoma and glaucoma in both eyes.
      The risk factors affecting glaucoma have also been found in patients with myopia,
      family history of glaucoma, low ocular perfusion pressure, systemic hypotension,
      cardiovascular disease, cerebrovascular disease, systemic hypertension, and high
      blood cholesterol. The efforts to study the glaucoma risk factors offer insight
      into the etiology and clinical development processes of glaucoma and provide an
      improved therapeutic strategy for glaucomatous.

PMID- 19575978
TI  - [Dentin sensitivity: an oral symptom that should not be neglected].

PMID- 19575979
TI  - [Oral health suggestion on dental caries, periodontal diseases, dentin
      hypersensitivity, and malocclusion].

PMID- 19575980
TI  - [Evaluation of preparation of curved root canals using hand-used ProTaper].
AB  - OBJECTIVE: To evaluate the shaping ability of hand-used ProTaper on curved canals
      using Endodontic Cube. METHODS: Fifty-four curved root canals in vitro were
      selected and divided into three groups according to the curved degree (alpha),
      group A: 0 degrees < or = alpha < 25 degrees , group B: 25 degrees < or = alpha <
      40 degrees , group C: 40 degrees < or = alpha < 55 degrees . Endodontic Cube was
      assembled, and each sample was sectioned perpendicular to the axis of the tooth
      into four sections with Isomer-Buhler in low speed. Then the root canals were
      prepared with hand-used ProTaper. Before and after shaping, photograph of all the
      sections were taken under a stereomicroscope. Statistical analyses were
      performed. RESULTS: The dentin cutting quantity of the whole canal prepared with
      ProTaper in group B and C was larger than that of group A. The deviation distance
      of the whole canal prepared by ProTaper in group C was significantly larger than
      that in group A, and the deviation distance in middle portion larger than that in
      group B. The maintaining ability in the middle portion of group C by ProTaper was
      worse than that of group A and B. CONCLUSIONS: The curvature of root canal may
      increase the cutting quantity of the -dentin and reduce the ability of remaining
      original canal shape prepared by ProTaper.

PMID- 19575981
TI  - [Evaluation of root abnormity in patients with aggressive periodontitis].
AB  - OBJECTIVE: To explore a method for classifying root abnormality and to
      investigate the status of root abnormality in patients with aggressive
      periodontitis (AgP). METHODS: A total of 108 patients (2841 teeth) with AgP, 41
      patients (1135 teeth) with chronic periodontitis (CP) and 30 periodontal healthy
      subjects (840 teeth) were included in the study. The abnormality of roots was
      evaluated on a full set of periapical radiographs. A reference parameter of "root
      width" in the middle of root was introduced in this study for classifying various
      types of root abnormality. The root abnormality was categorized into five types:
      cone-root (incisor, premolar), slender-root, curved-root, maladjusted proportion
      of crown and root, and synergetic root. RESULTS: To compare with normal incisor
      root, the parameter of root width in cone-root incisor is much lower [up incisor:
      (0.04 +/- 0.01) and (0.10 +/- 0.03) cm; low incisor: (0.02 +/- 0.02) and (0.07 +/
      0.02) cm, P < 0.001], and root is shorter with maladjusted proportion of crown.
      To compare with normal root, the slender-root in low incisor and premolar cone
      root, the parameters of root width are also lower [low incisors: (0.02 +/- 0.02)
      and (0.07 +/- 0.02) cm; up premolar: (0.03 +/- 0.03) and (0.07 +/- 0.01); low
      premolar: (0.02 +/- 0.01) cm and (0.18 +/- 0.26) cm, P < 0.001]. The number (or
      percentage) of teeth with root abnormality in AgP group, CP group, and control
      group was 407 (14.3%), 57 (5.0%), and 31 (3.7%), respectively. Significant
      differences of percentage of teeth with root abnormality were found among the
      three groups. AgP group had the highest percentages of teeth with root
      abnormality, while the control group had the lowest percentage. CONCLUSIONS: The
      patients with aggressive periodontitis had more teeth with root abnormality than
      the patients with chronic periodontitis or healthy subjects. The root abnormality
      could be a local contributing factor for AgP patients.

PMID- 19575982
TI  - [Biologic effects of advanced oxidative protein products on the human gingival
      fibroblasts].
AB  - OBJECTIVE: To investigate the effects of advanced oxidative protein products
      (AOPP) on the proliferation, apoptosis and matrix metalloproteinase-1 (MMP-1)
      synthesis of the human gingival fibroblast (HGF). To explore the possible
      mechanism of the periodontal destruction acceleration in diabetes through AOPP
      mediated oxidative stress. METHODS: HGF were isolated by both tissue explant
      cultivation technique and enzyme digestion method. The culture media with 5, 50,
      100 mg/L AOPP-HAS were added into each experimental group, but the culture media
      in the control group didn't contain AOPP-HAS. MTT colorimetric assay and ELISA
      were used to measure the changes of HGF proliferation and the levels of MMP-1
      protein from HGF at different time periods, respectively. Seventy-two hours after
      co-culture with 50 mg/L AOPP-HSA, cell apoptosis was detected by flow cytometry
      with Annexin V/PI staining. RESULTS: Compared to the control group, the growth
      inhibition rate of HGF in 5, 50, 100 mg/L AOPP-HSA group was significantly
      different (P < 0.05). The peak value appeared at 48 hours of co-culture [(19.01
      +/- 6.28)%, (30.48 +/- 5.75)%, (39.75 +/- 4.60)%, respectively]. There was a dose
      dependent relationship between the growth inhibition rate and AOPP-HSA. No
      significant difference was detected on the apoptotic level between experimental
      group and the control (P > 0.05). The MMP-1 synthesis in 0.5, 5, 50, 100 mg/L
      AOPP-HAS group [(55.61 +/- 1.06), (65.78 +/- 4.04), (79.24 +/- 3.09), (89.76 +/-
      28.88) mg/L, respectively] was significantly higher than that in the control
      [(34.90 +/- 3.15) mg/L] after 72 hours co-culture (P < 0.05). There was a dose
      dependent relationship between MMP-1 and AOPP-HSA. CONCLUSIONS: AOPP may inhibit
      the proliferation of HGF and such effect was not achieved through apoptosis. AOPP
      may increase collagen degradation by promoting MMP-1 synthesis and thus may
      accelerate periodontal destruction process in diabetes.

PMID- 19575983
TI  - [Effects of gingival fibroblasts transfected with human transform growth factor
      beta1 gene on improving the periodontal tissue regeneration].
AB  - OBJECTIVE: To evaluate the effects of gingival fibroblasts (GF) transfected with
      hTGF-beta1 gene on improving the periodontal tissue regeneration for the repair
      of degree II artificial furcation defects. METHODS: The gingival fibroblasts
      transfected with hTGF-beta1 gene was compounded to the cuttlebone-transformed
      nanometer hydroxyapatite (CBHA) material from the cuttlefish in vitro, the degree
      II furcation defects on the premolars of dogs were produced surgically, and the
      compound was to implanted into the defect (transfected group), and compared with
      the compound of periodontal ligament cells (PDLC) with nanometer HA material and
      the compound of untransfected GF with HA. The results were examined
      histologically 8 weeks after operation. RESULTS: In the transfected group and the
      positive control group, more new attachment was found compared with the negative
      control (P < 0.01), and the NC, NB and NC of the transfected group and the
      positive control group were: (2.97 +/- 0.50), (4.29 +/- 0.26) and (4.73 +/- 0.06)
      mm; (3.09 +/- 0.26), (4.46 +/- 0.25) and (4.69 +/- 0.10) mm, respectively. There
      was no significant difference between the two groups (P > 0.05). Although the
      alveolar bone regeneration was found in the untransfected group [NB = (3.46 +/-
      0.32) mm], the root resorption was observed. The tracing experiment showed that
      the transfected GF were found in the new alveolar bone and the periodontal
      membrane. CONCLUSIONS: GF transfected with hTGF-beta1 gene can significantly
      improve the periodontal tissue regeneration in treatment of degree II furcation
      defects and is involved in the formation of the new alveolar bone and the new
      periodontal membrane.

PMID- 19575984
TI  - [Expression and purification of human amelogenin mature peptide in Escherichia
      coli].
AB  - OBJECTIVE: To establish the expression and purification route for human
      amelogenin mature peptide in Escherichia coli and obtain the purified amelogenin
      (AMG) mature peptide. METHODS: Recombined plasmid pGEX-4T-1-AMG was transformed
      to Escherichia coli BL21. After expression, AMG was purified with glutathione S
      transferase fusion protein purification system (GSTrapFF) column. RESULTS: Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blotting hybridization results showed that 45,000 GST-AMG fusing protein and
      19,000 target AMG mature peptide were obtained successfully. CONCLUSIONS: pGEX-4T
      1-AMG-BL21 system is used successfully to express and purify human AMG mature
      peptide.

PMID- 19575985
TI  - [A pilot study on hypoxia of squamous cell carcinoma in oral cavity].
AB  - OBJECTIVE: To examine the extent of hypoxia in oral squamous cell carcinoma and
      investigate the factors related to the hypoxia. METHODS: An animal model of oral
      squamous cell carcinoma was established and single photon emission computed
      tomography (SPECT) with 99mTc-HL91 used to detect the hypoxia extent of the oral
      squamous cell carcinoma. The expression of hypoxia inducible factor 1 alpha (HIF
      1alpha) was examined by immunohistochemical staining in 42 cases of formalin
      fixed paraffin-embed squamous cell carcinoma. RESULTS: The uptake of 99mTc-HL91
      in the tumor tissue was higher than that in normal tissue and had linear relation
      with the tumor size (P < 0.05). There was no HIF-1alpha expression in the normal
      oral mucosa. The expression of HIF-1alpha was high in oral mucosa carcinoma and
      closely related to the differentiation degree of tumor and metastasis of lymph
      node (P < 0.05). CONCLUSIONS: Tumor tissue had broad hypoxic region. HIF-1alpha
      highly expressed in oral squamous cell carcinoma and may play an important role
      in carcinogenesis and aggression.

PMID- 19575986
TI  - [Correlation between the expression of cytokeratin-18-mRNA and invasion and
      metastasis of oral squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the relationship between the expression of cytokeratin
      (CK)-18 and biological behavior of oral squamous cell carcinoma (OSCC). METHODS:
      Twenty-three patients with OSCC were investigated for the expression of CK-18
      mRNA by semi-quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR). Correlations between clinical stages, pathological differentiation,
      lymphatic metastasis and the expression of CK-18-mRNA were evaluated. CK-18-mRNA
      expression of peripheral blood from the 23 patients and 23 healthy people were
      also examined. During follow-up after operation, the peripheral blood was
      collected again for the expression of CK-19-mRNA. RESULTS: Expression of CK-18
      mRNA was found in 16 patients. The expression of CK-18-mRNA was significantly
      associated with clinical stages, tumor differentiation and lymphatic metastasis.
      CK-18-mRNA was positive in 4 of 23 blood specimens before operation, but during
      follow-up only 1 of 23 patients was still positive in peripheral blood.
      CONCLUSIONS: CK-18 may provide additional information in forecasting the
      metastasis of OSCC and serve as a reference in monitoring recurrence.

PMID- 19575987
TI  - [Ultrasonographic evaluation of tongue movement during swallowing in severe
      skeletal Class III malocclusion in adult patients].
AB  - OBJECTIVE: To investigate the tongue movement during swallowing in skeletal Class
      III adult patients using M-mode ultrasonography combined with cushion scanning
      technique. METHODS: Tongue movement during swallowing in 20 skeletal Class III
      adult patients (11 females, 9 males, mean age 20.5 years) and 11 healthy adults
      (8 females, 3 males, mean age 23.5 years) was examined with M-mode
      ultrasonography combined with cushion scanning technique. The results were
      compared. RESULTS: Compared with mature swallowed, the skeletal Class III adult
      patients had longer phase 2 [(0.24 +/- 0.07) s], phase 3 [(1.17 +/- 0.21) s],
      longer total duration [(1.98 +/- 0.24) s], faster speed in phase 1 [(3.20 +/-
      1.30) mm/s], and smaller range in phase 5 [(0.38 +/- 0.28) mm]. CONCLUSIONS: The
      skeletal Class III adult patients had distinctly different tongue movements
      during swallowing.

PMID- 19575988
TI  - [Three-dimensional finite element analysis of stress distribution in mandible
      advanced with Forsus].
AB  - OBJECTIVE: To construct a three-dimensional finite element model of mandible and
      to analyze the stress distribution in mandible advanced with Forsus. METHODS: One
      growing patient with mandibular retrusion was selected. After leveling and
      aligning with MBT (Mclaughlin Bennett Treriri) straight-wire appliance to achieve
      the request of forsus with the spiral CT, a three-dimensional finite element
      model was constructed and the stress distribution in mandible after advancing at
      1 second, 15 seconds and 300 seconds was analyzed. RESULTS: The three-dimensional
      finite element model included MBT straight-wire appliance. The stress
      concentration areas were located in the front side of the condylar process, the
      sigmoid notch and mandibular molar areas at 15 seconds and 300 seconds after
      mandibular advancement. The maximum stress values were 34.47 MPa and 34.45 MPa,
      respectively. With the extension of loading time, the largest displacement
      increased from 3.30 x 10(-2) mm to 1.15 mm and the region of the largest
      displacement extended backwards along the body of mandible. However, the
      displacement of condyle reduced from 1.65 x 10(-2) mm at 1 second to 3.27 x 10(
      5) mm at 300 seconds after mandibular advancement. CONCLUSIONS: The three
      dimensional finite element model considered the viscoelasticity and
      viscoelasticity of mandibular. The result suggested that the stress distribution
      in the mandible gradually became stable after the application of Forsus and the
      appliance caused downward and forward mandibular modification.

PMID- 19575989
TI  - [The preparation of nano-hydroxyapatite and preliminary observation on its
      effects on the occlusion of dentinal tubule].
AB  - OBJECTIVE: To synthesize nano-hydroxyapatite (nano-HA) and evaluate its effect on
      the occlusion of dentinal tubules in vitro, and therefore provide evidence for
      the clinical application. METHODS: (NH(4))(2)HPO(4) and Ca(NO3)2 were used to
      form nano-HA, which was characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), Fourier transform infrared spectrometer
      (FTIR) and X-ray diffractometer (XRD) respectively. Twenty-four dentin slabs were
      obtained from 8 healthy third molars and randomly divided into 3 groups, which
      were control group, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)
      group, and nano-HA group. After the CPP-ACP and nano-HA were topically applied to
      the slabs of two study groups twice a day for 7 days, the surface of slab dentin
      was observed using SEM. RESULTS: SEM, TEM, FTIR, and XRD tests showed that nano
      HA was synthesized successfully. SEM observations revealed that the sealing of
      dentinal tubules of nano-HA group was extremely high when compared with those of
      control and CPP-ACP group. CONCLUSIONS: In comparison with CPP-ACP, nano-HA could
      occlude dentinal tubules more effectively in vitro.

PMID- 19575990
TI  - [Nav1.8 and Nav1.9 mRNA expression in rat trigeminal ganglion at different
      interval after molar extraction].
AB  - OBJECTIVE: To observe the expression and function of extraction. METHODS: Real
      time reverse transcription PCR paralleled with vitro-established cRNA standard
      curves was applied to measure the expression of Nav1.8, Nav1.9 at 30 min, 2 h, 1
      d, 3 d and 6 d respectively after extraction of rat right mandibular molars. The
      right mandibular molars were used as control. RESULTS: Both Nav1.8 and Nav1.9
      mRNA in right trigeminal ganglion showed little change after 30 min, and
      increased slowly after 2 h. Nav1.8, Nav1.9 mRNA expressions increased by 27% and
      24.5% respectively compared to the left trigeminal ganglion after 3 d, reaching
      the highest level (P < 0.05), and then the expressions began decreasing from 6 d.
      CONCLUSIONS: The pain caused by molar extraction is related to the up-regulation
      of expressions of sodium channels protein Nav1.8 and Nav1.9 mRNA, indicating the
      participation of sodium channels in regulations of peripheral tissue pain after
      molar extraction.

PMID- 19575991
TI  - [Intraoperative vessel thrombosis and its management in free flap transfers in
      head and neck region].

PMID- 19575992
TI  - [Treatment of Crouzon syndrome with combined intra- and extra-cranial approach].

PMID- 19575993
TI  - [Clinical application of ceramic restorations VIII. Clinical application of
      ceramic inlay].

PMID- 19575994
TI  - [Orthodontic treatment for adult: IV. Adjunctive orthodontic treatment prepared
      for final restoration and adult minor tooth movement].

PMID- 19575995
TI  - [Problem solving in endodontic diseases: I. Enamel developmental defects:
      clinical classification and molecular biologic mechanism].

PMID- 19575996
TI  - [Clinical trials in dentistry in the United States: I].

PMID- 19575997
TI  - [Neuroplasticity in patients with implant supported full dentures].
AB  - OBJECTIVE: To investigate the potential mechanism of "osseoperception" which is
      the sensory and motor experience associated with dental implants. METHODS: Twenty
      patients with implant supported full dentures or traditional full dentures were
      recruited in this study. Functional MRI (fMRI) scan covering the whole brain was
      carried out in these patients in clenching. The fMRI data were analyzed with SPM
      99 software. RESULTS: In implant supported removable denture group, increased
      blood oxygen level dependent (BOLD) signals during clenching were found in
      prefrontal cortex, premotor cortex, superior parietal cortex, basal ganglion and
      thalamus. In implant supported fixed denture group, main activations were found
      in prefrontal cortex, primary sensory and motor cortex, Broca's area, premotor
      cortex, superior temporal cortex, insular, basal ganglion, thalamus and
      hippocampus. In traditional full denture group, significant activations were
      mainly found in prefrontal cortex, premotor cortex. Their activation maps showed
      the greatest individually dependent diversity. CONCLUSIONS: Sensory and motor
      feedback of central nervous system in patients with implant support fixed
      dentures is close to that of natural dentition. Mastication with traditional full
      dentures is more likely a process of task learning, memory and adaptation, which
      might be a more individually dependent restoration.

PMID- 19575998
TI  - [Transgenic 4-1-BB ligand therapy induces tumor specific immune response in oral
      squamous cell carcinoma].
AB  - OBJECTIVE: To examine the activation and cytotoxicity of human peripheral blood T
      lymphocyte induced in vitro by human 4-1-BB ligand (4-1-BBL) gene transfected
      into tumor Tca8113 cells. METHODS: The eukaryotic expression vector pEGFP-h4-1
      BBL was transfected into human oral carcinoma cell line Tca8113 by Lipofectamine
      2000. The transfected cells were then selected in medium containing G-418, cloned
      by limited dilution and named as Tca8113-4-1-BBL. Human 4-1-BBL mRNA and protein
      expression of transfected cells was detected by reverse transcriptase-polymerase
      chain reaction (RT-PCR) and western blotting respectively. The tumor cell
      vaccines (TCV) were obtained by treatment with mitomycin (MMC). Human peripheral
      blood mononuclear cells (PBMC) were prepared from lymphoprep, and then stimulated
      with anti-CD-3 mAb and incubated with non-transfected or transfected TCV-Tca8113
      cells, respectively. The proliferation of T cells was evaluated by trypan blue
      exclusion; the CCK-8 was used to detect the cytotoxic effect of T lymphocytes.
      Meanwhile, the secretion of interferon-gamma (IFN-gamma) and interleukin (IL)-2
      in culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The Tca8113 cells transfected by pEGFP-h4-1-BBL could express human 4-1
      BBL efficiently. As compared with wild type Tca8113 cells, the transfected
      Tca8113 cells could markedly promote proliferation, IL-2 and IFN-gamma production
      and cytotoxic activity of lymphocytes. CONCLUSIONS: The transfection of human 4-1
      BBL gene in Tca8113 cells is effective in enhancing its immunogenicity and
      inducing antitumor immune response in vitro.

PMID- 19575999
TI  - [Effects of Ezrin gene on the proliferation and invasion activity of human
      salivary gland adenoid cystic carcinoma].
AB  - OBJECTIVE: To examine the expression of Ezrin in human salivary gland adenoid
      cystic carcinoma and investigate the effects of Ezrin gene silence on cell
      proliferation, apoptosis and invasion of adenoid cystic carcinoma (ACC)-M.
      METHODS: The expression of Ezrin was detected by immunohistochemistry in normal
      salivary gland tissue (n=15), pleomorphic adenoma (n=40) and salivary gland
      adenoid cystic carcinoma (n=43). The Ezrin Stealth RNAi Duplex, containing
      Stealth RNAi Negative Control Duplex were constructed and transfected into ACC-M
      cells by Lipofectamine 2000. The expression levels of Ezrin were detected by RT
      PCR and immunohistochemistry. The cell cycle and apoptosis rate were analyzed by
      flow cytometry (FCM). The cell proliferation was detected by methyl thiazolyl
      tetrazolium (MTT) and cell invasion by Transwell test. RESULTS: The positive rate
      of Ezrin expression in ACC was significantly higher than that in normal salivary
      gland tissue and pleomorphic adenoma (P<0.05). After transfection of Ezrin
      Stealth RNAi Duplex, the mRNA and protein expression of Ezrin were down
      regulated, the cell proliferation activity was inhibited, the G0-G1 Phase cells
      were increased, and the apoptosis rate of Ezrin Stealth RNAi Duplex group was
      higher than that in control groups and cell invasion ability was decreased.
      CONCLUSIONS: Over expression of Ezrin in human salivary gland adenoid cystic
      carcinoma may promote genesis, development and metastasis of tumors. Ezrin
      Stealth RNAi Duplex could efficiently down-regulate the expression of Ezrin gene,
      and partly inhibited proliferation of ACC-M cells, induce apoptosis and decrease
      invasion ability of these cells in vitro.

PMID- 19576000
TI  - [Prevalence of dental erosion and associated drinks in 12-year-old population of
      Beijing].
AB  - OBJECTIVE: To investigate the prevalence of dental erosion and associated drinks
      in 12-year-old adolescence of Beijing. METHODS: A random sample of 12-year-old
      adolescence of Beijing (n=844) was examined for dental erosion and required to
      fill a questionnaire of acidic drink intake. The grade criteria suitable for the
      survey of the dental erosion was used in the study. RESULTS: The prevalence of
      dental erosion was 61.8%, of which mild enamel was 74.1%, severe enamel erosion
      24.9% and dentine erosion 1.0%. Statistic analysis showed that a large amount of
      intake of carbonated drink or juice were risk factors. CONCLUSIONS: Attention
      should be paid to the prevalence of dental erosion among Chinese adolescence.

PMID- 19576001
TI  - [A differential expression proteomic study of human periodontal ligament cell
      during osteogenic differentiation].
AB  - OBJECTIVE: To obtain regulating proteins during human periodontal ligament cell
      (hPDLC) osteogenic differentiation and investigate its underlying molecular
      mechanism. METHODS: Two-dimension difference in gel electrophoresis (2D-DIGE)
      coupled with matrix-assisted laser adsorption ionization-time of flight mass
      spectrometry (MALDI-TOF-MS) analysis was used to identify regulating proteins
      during hPDLC osteogenic differentiation. RESULTS: A differently expressed protein
      profile was obtained 7 days after osteogenic induction, and 61 protein spots with
      significant differences, 29 protein spots were identified by MALDI-TOF-MS,
      including cytoskeleton, cell membrane-bounding, nuclear regulation, matrix
      synthesis, and metabolic enzymes and signal transduction and other proteins. A
      functional class of cytoskeleton proteins showed co-regulation, these proteins
      were intimately involved in the reorganization of the cytoskeleton, cytokinesis
      and migration during PDLC differentiation. CONCLUSIONS: A database of differently
      displayed proteins during hPDLC osteogenic differentiation was established, which
      may be helpful to understand and further study molecular mechanism of PDLC
      osteogenic differentiation.

PMID- 19576002
TI  - [Relationship between the impacted mandibular third molar and the mandibular
      canal on panoramic radiograph and cone beam computed tomography].
AB  - OBJECTIVE: To investigate the actual relationship between the impacted mandibular
      third molars (IMTM) and the mandibular canals on panoramic radiographs and cone
      beam computed tomography (CBCT). METHODS: A cross-sectional study design was used
      and panoramic radiographs of 390 patients (645 sides developed IMTM) were
      included in the present study. The relationship between the IMTM and the
      mandibular canal on panoramic radiographs was defined in three types:
      'untouched', 'touching in point', and 'superimposition or line touching'. The
      IMTM superimposing and line touching with mandibular canals on panoramic
      radiographs were examined by CBCT. RESULTS: The relationship types on panoramic
      radiographs were as follows: 'untouched' type 441 IMTM (68.4%), the type of
      'touching in point' 149 IMTM (23.1%) and the type of 'superimposition and line
      touching' 55 IMTM (8.5%). CBCT showed that 25 (50%) of 50 IMTM of superimposition
      and line touching type impinged on the mandibular canals. CONCLUSIONS: More than
      90% of IMTM which do not have intimate relationship with the mandibular canals
      can be screened out by panoramic radiographs. The IMTM which belong to the line
      touching and superposition type on panoramic radiographs should be examined by
      CBCT.

PMID- 19576003
TI  - [Effects of simvastatin on the immune-related genes of mouse osteoblasts].
AB  - OBJECTIVE: To investigate the expression of immune-related genes during
      osteogenesis stimulated by simvastatin. METHODS: After treated with simvastatin,
      the expression of immune-related genes of mouse osteoblast was examined with gene
      chip (BiostarM-140s). RESULTS: There were 16 differently expressed genes related
      to immune function, with nine down-regulated genes and seven up-regulated genes.
      CONCLUSIONS: After treated with simvastatin, expression of inflammation related
      genes is down-regulated and inflammation inhibitor genes is up-regulated in mouse
      osteoblasts.

PMID- 19576004
TI  - [Gene mutation and expression of SH-3BP-2 in cherubism].
AB  - OBJECTIVE: To detect the mutation and expression of SH-3BP-2 in Chinese patients
      of cherubism and to investigate the possible relationship of gene mutation and
      multinucleated giant cells in lesions. METHODS: Genomic DNA was extracted from
      paraffin-imbedded tissues and peripheral blood samples of 10 cases of cherubism
      (6 familial cherubism and 4 sporadic cherubism). SH-3BP-2 mutations were detected
      by PCR-direct sequencing. The nature of multinucleated giant cells in lesions was
      detected by enzyme histochemical staining and immunohistochemical staining using
      paraffin-imbedded tissues sections. The SH-3BP-2 protein was detected by
      immunohistochemical staining. RESULTS: Three missense mutations (G1520A, G1505A,
      G1505C) in exon 9 of SH-3BP-2 were identified which led to 3 transitions
      (Gly420Glu, Arg415Gln, Arg415Pro). There were no abnormalities in exon 3 of SH
      3BP-2 except 1 case which had not PCR products. The protein SH-3BP-2, the
      calcitonin receptor and the tartrate-resistant acid phosphatase were detected in
      the cytoplasm of all multinucleated giant cells and parts of monokaryon matrix
      cells in 8 paraffin-imbedded samples. CONCLUSIONS: The SH-3BP-2 mutation may
      participate in the differentiation and maturation of osteoclast-like cells in the
      lesion of cherubism.

PMID- 19576005
TI  - [Analysis of the difference in the tissue surfaces between the old and new upper
      complete dentures].
AB  - OBJECTIVE: To investigate the reduction in residual ridges of maxillary
      edentulous models duplicated from old and new complete dentures using the 3-D
      data analysis. METHODS: Twenty-six pairs of maxillary edentulous models copied
      from the fitting surfaces of new and old upper complete dentures were selected
      for this study. The 3-D data were collected with a laser scanning system. The
      data were matched using Geomagic Studio 8 and Rapidform2006 software and then the
      fitting surfaces of new complete dentures were analyzed in comparison with old
      ones. RESULTS: The total amount of morphologic change of fitting surface [(39.8+/
      14.2)%] was greater than the change of width [(28.2+/-16.0)%]; the area reduction
      of the residual ridge in anterior region [(43.0+/-15.2)%] was larger than that in
      posterior region [(36.1+/-14.1)%]; and the area reduction of residual ridge in
      buccal aspect [(42.9+/-13.8)%] was larger than that in lingual aspect [(35.5+/
      15.2)%]. All the differences were statistically significant (P<0.05).
      CONCLUSIONS: The results of this study reveal that 3-D analysis of the whole
      change of the residual ridge is significant and verify that the residual ridge
      resorption of edentulous maxilla in three dimensions is greater in buccal aspect
      than in lingual aspect and greater in anterior region than in posterior region.

PMID- 19576006
TI  - [Effects of magnetron sputtered ZrN on the bonding strength of titanium
      porcelain].
AB  - OBJECTIVE: To investigate the effect of magnetron sputtered ZrN on the bonding
      strength between a low-fusing porcelain (Ti/Vita titankeramik system) and
      commercially pure cast titanium. METHODS: Sixteen specimens were randomly
      assigned to test group and control group (n=8). The control group received no
      surface treated. Magnetron sputtered ZrN film was deposited on the surface of
      specimens in the test group. Then the sixteen titanium-porcelain specimens were
      prepared in a rectangular shape and went through three-point bending test on a
      universal test machine. The bond strength of Ti/porcelain was recorded. The phase
      composition of the specimens was analyzed using X-ray diffraction (XRD). The
      interface at titanium and porcelain and the titanium surface after debonding were
      observed with a scanning electron microscopy (SEM) and analyzed using energy
      depressive spectrum (EDS). RESULTS: New phase of ZrN was found with XRD in the
      test group. Statistical analysis showed higher bond strength following ZrN
      surface treatment in the test group [(45.991+/-0.648) MPa] than that in the
      control group [(29.483+/-1.007) MPa] (P=0.000). Bonded ceramic could be observed
      in test group, the amount of bonded ceramic was more than that in the control
      group. No obvious bonded ceramic in control group was found. CONCLUSIONS:
      Magnetron sputtered ZrN can improve bond strength of Ti/Vita titankeramik system
      significantly.

PMID- 19576008
TI  - [Rights maintenance and self-discipline of practicing dentist: Part XVIII.
      Responsibility for quoting proof in lawsuits for medical care dissension].

PMID- 19576007
TI  - [Effects of tetrapod-like zinc oxide whiskers incorporation on antibacterial
      activity of composite resin].
AB  - OBJECTIVE: To evaluate effects of incorporating tetrapod-like zinc oxide whisker
      (T-ZnOw) antibacterial agent on the antibacterial activity of composite resin,
      compared with that of the silver-based inorganic antibacterial agent. METHODS:
      The minimal inhibitory concentration (MIC) and minimal bactericidal concentration
      (MBC) of the two different antibacterial agents against Streptococcus mutans were
      investigated using the broth dilution test. Then the antibacterial activities of
      the self-cured composite resin specimens with different incorporating
      concentrations of the two antibacterial agents were evaluated using direct
      contact test. And the antibacterial activities of the resin specimens were
      examined again after 3 months of accelerating aging. RESULTS: The MIC (MBC) of
      the T-ZnOw antibacterial agent and silver-based inorganic antibacterial agent
      were 0.15625 (0.3125) g/L and 0.15625 (0.15625) g/L. When the concentrations of T
      ZnOw added to composite resin were 3%, 5%, and 10% (w/w), the antibacterial
      ratios of the resin specimens were (84.85+/-5.16)%, (94.22+/-3.73)%, and (99.43+/
      0.48)% respectively. When the concentrations of the silver-based antibacterial
      agent added to composite resin were 1%, 3%, and 5%, the antibacterial ratios were
      (71.01+/-7.67)%, (90.76+/-5.91)%, and (97.19+/-4.10)% respectively. The
      antibacterial ratios of the resin specimens containing 5% of both antibacterial
      agents were (89.89+/-5.55)% and (78.79+/-7.81)% respectively after 3 months of
      accelerating aging. CONCLUSIONS: Incorporation of the T-ZnOw antibacterial agent
      in composite resin can improve the antibacterial performance of the resin, and
      the resin exhibits better antibacterial performance than that incorporating
      silver-based inorganic antibacterial agent after 3 months of aging.

PMID- 19576009
TI  - [Orthodontic treatment for adult: Part III. Principles and methods of orthodontic
      for adult with temporomandibular disorder].

PMID- 19576010
TI  - [Progresses in studies on association between psychological factors and oral
      lichen plans].

PMID- 19576011
TI  - [Fiber types and transition of jaw-opening and jaw-closing muscles].

PMID- 19576012
TI  - [Pay more attention to prevention and management of dentin hypersensitivity].

PMID- 19576013
TI  - [Diagnosis criteria of oral submucous fibrosis (Draft)].

PMID- 19576014
TI  - [Guideline for the diagnosis and management of dentin hypersensitivity].

PMID- 19576015
TI  - [Research on the correlation of vascular endothelial growth factor and dendritic
      cell in patients with oral squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF)
      on the differentiation, formation and function of the dendritic cell (DC) in
      peripheral blood of patients with oral squamous cell carcinoma (OSCC). METHODS:
      Flow cytometry was used to detect the number of DC in peripheral blood of 81
      patients with OSCC, and ELISA applied to test serum VEGF concentration the OSCC
      patients, and immunohistochemistry used to observe the expression of VEGF in
      primary foci of 57 patients with OSCC. DC from CD-14 peripheral blood mononuclear
      cells were cultured with VEGF(165) in vitro to investigate the cytokine's effect
      on DC. RESULTS: In comparison with controls [(325.70 +/- 117.54) ng/L], the level
      of serum VEGF [(764.33 +/- 263.64) ng/L] was significantly increased (P < 0.01)
      and the DC numbers was significantly decreased (P < 0.01) in patients with OSCC.
      There was a negative correlation between serum VEGF concentration and the level
      of DC (P < 0.01). The expression of VEGF in primary focus was positively
      correlated with serum VEGF concentration, but was negatively correlated with the
      level of peripheral blood DC (P < 0.01). DC cultured in vitro with VEGF(165)
      decreased the expression of CD-1a, CD-40, CD-80, CD-86, CD-83, HLA-DR, and
      revealed a lower ability of stimulating T lymphocyte proliferation but a higher
      ability of uptake, compared to controls. CONCLUSIONS: The overexpressed VEGF in
      patients with OSCC might be one of the important reasons for blocking the
      differentiation and maturation of DC.

PMID- 19576016
TI  - [Celecoxib enhances the lethal effects of bleomycin in human tongue squamous
      carcinoma cell line Tca8113].
AB  - OBJECTIVE: To investigate the role of COX-2 inhibitor celecoxib in enhancing the
      lethal effects of bleomycin in Tca8113 cell line. METHODS: Tca8113 cells were
      treated with different concentrations of celecoxib and bleomycin for 24, 48, 72
      h. Methyl thiazolyl tetrazolium assay was used to calculate cell growth
      inhibition rate and Jin Zheng Jun's method was used to evaluate the interaction
      of celecoxib and bleomycin on Tca8113 cells. Flow cytometry was used to evaluate
      the effects of combined use of celecoxib and bleomycin on cell cycle progress and
      apoptosis. RESULTS: Low dose of celecoxib (10 micromol/L, < IC(50)) combined with
      bleomycin showed synergism or additive lethal effect on Tca8113 cell line.
      Celecoxib could notably enhance the inhibitory effect of bleomycin on Tca8113
      cells by blocking cell cycle progress and thus resulting in the increasing
      G(0)/G(1) cells [(60.93 +/- 0.32)%] distribution and inducing apoptosis [(1.87 +/
      0.11)%]. CONCLUSIONS: Low doses of celecoxib could significantly enhance the
      lethal effect of bleomycin on Tca8113 cells by inhibiting cell growth and
      proliferation through blocking cell cycle progress and inducing apoptosis. The
      ways of these interactions on inhibiting Tca8113 cell growth were synergistic
      or/and additive.

PMID- 19576017
TI  - [Whole-body diffusion weighted imaging manifestation of oral squamous cell
      carcinoma with metastatic lymph nodes].
AB  - OBJECTIVE: To investigate the manifestation of oral squamous cell carcinoma with
      metastatic lymph nodes in whole-body diffusion weighted imaging (WB-DWI) and its
      clinical significance. METHODS: Twenty-one cases of oral squamous cell carcinoma
      with metastatic lymph nodes were examined by WB-DWI, of which 19 were scanned
      with routine MRI, 9 cases examined by positron-emission tomography (PET). All
      cases were confirmed by pathology. MRI scan covered whole body and built whole
      body diffusion image after reconstruction with GE HDe 1.5T MRI scanner. RESULTS:
      There were 139 metastatic lymph nodes, 11 normal lymph nodes, and 21 inflammatory
      lymph nodes exhibited by WB-DWI in 21 cases. Metastatic lymph nodes showed higher
      signal and lower value of apparent diffusion coefficient (ADC). The mean ADC
      value of metastatic lymph nodes (0.78 +/- 0.07) was significantly lower than that
      of inflammatory (1.18 +/- 0.15) and normal nodes (1.78 +/- 0.16), and normal
      nodes showed even higher levels of ADC value. CONCLUSIONS: STIR-EPI-DWI is a new
      promising technique for differentiating normal, inflammatory, and metastatic
      lymph nodes and can provide more useful information on lymph node metastasis.

PMID- 19576018
TI  - [Reliability of venae comitant of facial artery as the donor vein in
      microvascular autologous submandibular gland transfer].
AB  - OBJECTIVE: To analyse the reliability of concomitant venae of facial artery as
      the donor vein in microvascular autologous submandibular gland transfer. METHODS:
      One hundred and seventeen cases with severe keratoconjunctivitis sicca treated by
      microvascular transfer of autogenous submandibular gland transfer from August of
      1999 to November of 2007 were reviewed. The cases were divided into three groups
      according to their different donor veins, with group A using facial veins, group
      B using concomitant venae of facial artery, and group C using a vein near the
      duct. Group A and B were compared in terms of venous thrombosis rate and failure
      rate related to venous thrombosis. RESULTS: Among 117 cases, there were 122 sides
      of submandibular gland transfers, with 93 in group A, 27 in group B, and 2 in
      group C. Postoperative venous thromboses rate was 15% in group A and 7% in group
      B, with significant difference (P < 0.01). The failure rate of transferred gland
      related to venous thrombosis was 8% in group A, and 7% in group B, with no
      significant difference (P > 0.05). CONCLUSIONS: Concomitant venae of facial
      artery can be used as reliable donor vein in microvascular autologous
      submandibular gland transfer.

PMID- 19576019
TI  - [Serum C-reactive protein levels and lipid profiles concentrations in moderate to
      severe periodontitis and coronary heart disease: a comparative study].
AB  - OBJECTIVE: To investigate the correlation between moderate to severe
      periodontitis and coronary heart disease (CHD) and to examine the serum C
      reactive protein (CRP) levels in subjects with CHD and/or moderate to severe
      periodontitis. METHODS: Serum CRP levels, serum lipids [low density lipoprotein
      cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), total
      cholesterol (TC) and triglyceride (TG)] and clinical periodontal parameters
      [clinical attachment loss (CAL), probing depth (PD), and bleeding on probing
      (BOP)] were measured and analyzed in coexistent moderate to severe periodontitis
      and CHD patients (n = 47), CHD patients (n = 28), moderate to severe
      periodontitis patients (n = 40), and healthy subjects (n = 40). RESULTS: The
      serum CRP levels in control group, moderate to severe periodontitis patients, CHD
      patients and patients with both diseases were (1.30 +/- 0.15), (2.44 +/- 0.18),
      (5.99 +/- 0.82) and (6.88 +/- 0.71) mg/L, respectively. The differences among
      these four groups were significant (P < 0.001). The multivariate logistic
      regression revealed that moderate to severe periodontitis patients exhibited
      markedly elevated odds of having CHD (OR = 2.417, 95% CI: 1.126 - 6.659). The
      total cholesterol levels were also significantly different among the four groups
      (P = 0.017). CONCLUSIONS: The moderate to severe periodontitis was associated
      with elevated serum CRP levels which may in turn affect the initiation and
      progression of CHD, and may be a risk factor for CHD.

PMID- 19576020
TI  - [Stress analysis of the all-ceramic crown with a numerical approach].
AB  - OBJECTIVE: To analyze the stress distribution in all-ceramic crowns when it was
      subjected to load. METHODS: A 3D numerical model of the all-ceramic crown of the
      right mandibular first molar was generated from scanned CT images. Finite element
      analysis (FEA) was used to evaluate the stress distribution in the all-ceramic
      crown when it was subjected to 5 load conditions. RESULTS: Stress distributions
      under 5 loading conditions were obtained. Stress concentrations were generally
      found near the loading areas at the veneer and at the lower surface of the core
      beneath the loading areas. In the 5 loading conditions, it was found that when
      the crown was loaded with vertical concentrated load, the tensile stresses around
      the shoulder areas were uniform, while stress concentration with maximum of 32.25
      MPa was found at the shoulder areas in lingual-buccal direction when loads were
      applied at an angle of 10 degrees with the tooth axis on the buccal side. The
      masticatory load which was applied at 20 degrees with the tooth axis on the
      buccal side would cause stress concentration at the shoulder in mesial-distal
      direction. The maximum value could reach 11.29 MPa. CONCLUSIONS: The occlusal
      surface of the all-ceramic crown must be trimmed to increase multiple contact
      zones with the opposite surfaces in antagonist teeth to avoid excessive
      concentrated stress that may cause crown failure.

PMID- 19576021
TI  - [Ultrastructural study of sclerotic dentin surface following the application of
      the Er, Cr: YSGG laser].
AB  - OBJECTIVE: To investigate the ultrastructure character of sclerotic dentin
      surface conditioned by the Er, Cr: YSGG laser and acid etching. METHODS: Sixteen
      human teeth with sclerotic dentin were randomly assigned to 4 groups, and
      conditioned with acid etching (Group A), laser irradiation (Group B), laser
      irradiation after acid etching (Group C), or acid etching after laser irradiation
      (Group D) respectively. The characters of surface ultrastructure were observed
      using scanning electron microscope (SEM). RESULTS: In Group A, the majority of
      dentin tubules were blocked by sclerotic rods. In Group B, the honeycomb-like
      change was found on the sclerotic dentin surface. The surface structure of Group
      C was similar to that of Group B. In group D etching wiped off the honeycomb-like
      structure. CONCLUSIONS: The sclerotic dentin surface treated with laser
      irradiation turns into uniform honeycomb-like structure. The rough surface may be
      beneficial to bonding strength on sclerotic dentin after laser irradiation.

PMID- 19576022
TI  - [A preliminary study of murine hemangioma model by delivery of recombinant adeno
      associated virus mediated human vascular endothelial growth factor-121 gene].
AB  - OBJECTIVE: To investigate the feasibility of establishing a murine hemangioma
      model with injection of recombinant adeo-associated virus mediated human vascular
      endothelial growth factor-121 (rAAV-hVEGF(121)) gene. METHODS: rAAV-hVEGF(121)
      was constructed, identified and then implanted to the left back ear of each mouse
      (1.0 x 10(11)VG in 50 microl per mouse and 10 nude mice received the injection),
      the rights served as controls with an injection of the same volume of phosphate
      buffered solution (PBS). The skin color and swelling of left back ear were
      observed every other day. Histological examination was carried out after mice
      were sacrificed 2, 4, 6, 8, 12 weeks after injection. RESULTS: The rAAV
      hVEGF(121) was correctly constructed and confirmed by restriction endonuclease
      analysis, polymerase chain reaction and DNA sequencing analysis. The skin of left
      back ear became red 2 weeks after injection and gradually exhibited a red lump
      which was at its utmost 12 weeks after injection. Such phenomena were not
      observed in right back ear. Histological examinations showed aggregates of
      endothelial cells by 2 weeks and at 8 weeks the swollen tissue contained many
      cysts filled with a mass of red cells. CD-34 staining suggested most of the newly
      formed cells were endothelial cells. CONCLUSIONS: A hemangioma model was
      established in mice with injection of recombinant rAAV-hVEGF(121) gene.

PMID- 19576023
TI  - [Evaluation of shear bond strengths of self-etching and total-etching dental
      adhesives to enamel and dentin].
AB  - OBJECTIVE: To evaluate the shear bond strengths of four dental adhesives in
      vitro. METHODS: The facial surfaces of 20 human maxillary incisors were prepared
      to expose fresh enamel and randomly divided into four groups, in each group 5
      teeth were bonded with one adhesives: group A (Clearfil Protect Bond, self
      etching two steps), group B (Adper( Prompt, self-etching one step), group C
      (SwissTEC SL Bond, total-etching two steps), group D (Single Bond, total-etching
      two steps). Shear bond strengths were determined using an universal testing
      machine after being stored in distilled water for 24 h at 37 degrees C. RESULTS:
      The bond strengths to enamel and dentin were (25.33 +/- 2.84) and (26.07 +/-
      5.56) MPa in group A, (17.08 +/- 5.13) and (17.93 +/- 4.70) MPa in group B,
      (33.14 +/- 6.05) and (41.92 +/- 6.25) MPa in group C, (22.51 +/- 6.25) and (21.45
      +/- 7.34) MPa in group D. Group C showed the highest and group B the lowest shear
      bond strength to enamel and dentin among the four groups. CONCLUSIONS: The two
      step self-etching adhesive showed comparable shear bond strength to some of the
      total-etching adhesives and higher shear bond strength than one-step self-etching
      adhesive.

PMID- 19576025
TI  - [Puzzle and consideration about educational and degree system in stomatology in
      modern China].

PMID- 19576024
TI  - [Expression of survivin, Bcl-2 and p53 during 4-nitro-quinoline 1-oxide-induced
      rat tongue carcinogenesis].
AB  - OBJECTIVE: To investigate the expression of survivin during oral carcinogenesis
      and its relationship with the expression of Bcl-2 and p53. METHODS: Two-step
      immunohistochemical method was employed to detect the expression of survivin, Bcl
      2 and p53 in 60 rat tongue carcinogenesis specimens induced by 4-nitro-quinoline
      1-oxide (4NQO). RESULTS: Survivin was present in 1/36 cases of normal mucosa,
      6/11 cases of oral epithelial dysplasia and 10/11 cases of oral carcinoma. There
      were significant difference in the expression of survivin among normal mucosa,
      oral epithelial dysplasia and carcinoma (P < 0.001). While in the 17 cases of
      positive expression of survivin, Bcl-2 was present in 12 cases and p53 was
      present in 8 cases. The expression of survivin in oral epithelial dysplasia and
      carcinoma were significantly higher than that in normal oral mucosa (P < 0.01).
      The expression of survivin was positively correlated to the expression of Bcl-2
      and p53 in rat tongue (P < 0.01). CONCLUSIONS: The expression of survivin may
      play an important role in oral carcinogenesis. Survivin, Bcl-2 and p53 may be
      synergetic in the carcinogenesis of oral cancer.

PMID- 19576026
TI  - [Unconventional extraction of trauma-caused root ankylosis of maxillary central
      incisors].

PMID- 19576027
TI  - [Clinical application of ceramic restorations VII. Classification and application
      of ceramic materials].

PMID- 19576028
TI  - [Orthodontic treatment for adult: Part II. Management and treatment for the
      orthodontic patient with periodontal problems].

PMID- 19576029
TI  - [Disinfection of dental impressions].

PMID- 19576030
TI  - [Development of the studies on the antibacterial activity of intra-cellular
      antibiotics].

PMID- 19576031
TI  - [A brief report on the 3rd International Congress on Adhesive Dentistry].

PMID- 19576032
TI  - [Efforts for management of chronic obstructive pulmonary disease should become an
      obligation among Chinese medical workers].

PMID- 19576033
TI  - [Clinical significance of bronchial reversibility test in the diagnosis and
      treatment of chronic obstructive pulmonary disease].

PMID- 19576034
TI  - [New advance in the management for pulmonary hypertension in chronic obstructive
      pulmonary disease].

PMID- 19576035
TI  - [The quality of life of patients with chronic obstructive pulmonary disease and
      correlated factors].
AB  - OBJECTIVE: To evaluate the quality of life (QOL) of patients with chronic
      obstructive pulmonary disease (COPD) and correlated factors. METHODS: Data of 20
      245 patients with COPD were collected from the cross-sectional survey of COPD,
      which was conducted between 2002 and 2004 in urban and rural areas of Beijing,
      Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shanxi for residents aged
      over 40 years old. The recruited populations were interviewed with questionnaire
      and tested for spirometry. The quality of life was assessed with 12-item short
      form health survey questionnaire (SF-12). Those with less than 70% of post
      bronchodilator FEV(1)/FVC were identified as having COPD. The differences between
      groups in SF-12 scores converted by rank were compared using general linear
      model. Stepwise multiple linear regressions were conducted to study the main
      determinants of QOL. RESULTS: Compared to subjects without COPD, those with COPD
      had impaired QOL (56 +/- 7 vs. 57 +/- 6 in mental component scores, F = 4.442, P
      < 0.05; 46 +/- 9 vs. 50 +/- 6 in physical component scores, F = 453.960, P <
      0.05). Among COPD patients, the mental component score was associated with scores
      of dyspnea, BMI, comorbidities, sex and living areas, while the physical
      component score was associated with scores of dyspnea, severity of COPD,
      comorbidities, exposure to dusts/gases/fumes, sex, age, educational level and
      previous diagnosis of respiratory diseases (all P < 0.05). CONCLUSIONS: The QOL
      in patients with COPD was impaired and associated with scores of dyspnea,
      severity of COPD, comorbidities and BMI. Improvement of dyspnea, nutritional
      support, prevention of comorbidities and keeping away from risk factors may
      improve the QOL in COPD patients.

PMID- 19576036
TI  - [Impact of chronic obstructive pulmonary disease on quality of life and economic
      burden in Chinese urban areas].
AB  - OBJECTIVE: To assess the impact of chronic obstructive pulmonary disease (COPD)
      on the quality of life and economic burden in Chinese urban areas. METHODS: COPD
      patients (n = 723) were interviewed face-to-face in outpatient departments in 6
      large cities in China. The questionnaire included social and demographic
      information, current health status, quality of life (SGRQ), and medical
      expenditure on outpatient visit, hospitalization, medicine purchasing in medicine
      stores in the last 12 months, and other expenditures related with COPD were also
      collected. All the data were analyzed using descriptive method. RESULTS: Of the
      723 COPD patients interviewed, 73% were male and the average age was 67 years
      old. The average symptom score of SGRQ was 49 +/- 24, activity score 57 +/- 23,
      impact score 46 +/- 23 and total score 50 +/- 21, which were all higher than
      scores of the healthy populations. The average direct medical cost (including
      outpatient cost, inpatient cost, and medicine purchasing cost) was 11 744 RMB
      yuan annually. The direct non-medical cost (including transportation fee,
      nutrition fee, and nursing fee) was 1570 RMB yuan. 36% of the patients in work
      had an average of 17 working days lost in the last 12 months because of COPD,
      while 17% of their relatives had an average of 14 working days lost for caring
      the patients. CONCLUSIONS: COPD has a serious impact on the quality of life of
      Chinese urban patients and places a heavy economic burden on their family and the
      society. Management of COPD should be improved for patients at stable conditions,
      so as to reduce the incidence and exacerbation of COPD.

PMID- 19576037
TI  - [Costs of the last hospitalization for patients with acute exacerbation of
      chronic obstructive pulmonary disease and patients with lung cancer].
AB  - OBJECTIVE: To examine the cost for patients who died in hospital with acute
      exacerbation of chronic obstructive pulmonary disease (AECOPD) compared with
      those died with lung cancer, and to examine their variations. METHODS: A
      retrospective cohort study was performed. The patients who died in hospital
      between January in 2003 and December in 2007 were enrolled. Statistical analysis
      was performed using the SPSS 13.0. RESULTS: Totally 416 patients were enrolled,
      with 86 COPD patients and 330 lung cancer patients. Patients with COPD were older
      than those with lung cancer. The incidences of co-morbidities such as coronary
      artery disease, hypertension, cerebrovascular disease, respiratory failure and
      lung infection in AECOPD patients were higher than those in lung cancer patients.
      Second malignant neoplasm of important organs was found in 211 patients (63.94%)
      with lung cancer. In the last hospitalization, the total amount of direct medical
      costs was higher for patients with AECOPD than for patients with lung cancer [74
      143 (102 608) RMB vs 37 810 (51 374) RMB], z = 2.48, P < 0.05, especially for the
      treatment cost [(19 324 (61 843) vs 5876 (9764), z = 4.55, P < 0.01] and the
      laboratory cost [7976 (18 397) vs 3397 (4096), z = 5.97, P < 0.01]. There was no
      significant difference in the constituents of the cost between COPD and lung
      cancer patients (chi(2) = 8.23, P > 0.05). The percentage of the drug cost to the
      total cost was the highest, followed by the treatment cost and the auxiliary
      examination cost. The ratio of the drug cost to the total cost was lower in COPD
      patients (37.2 +/- 12.6)% vs (53.8 +/- 17.6)%, t = 7.34, P < 0.01, while the
      constituent ratio of treatment cost was higher in COPD than in lung cancer
      patients CONCLUSIONS: There was significant variability in healthcare resource
      utilization between COPD and lung cancer patients in their last hospitalization
      of life, the main reason of which was the increased costs of maintenance of life.

PMID- 19576038
TI  - [Clinical, pathological and radiological characteristics of 83 cases of pleural
      tuberculoma].
AB  - OBJECTIVE: To investigate the clinical, pathological and radiological
      characteristics of pleural tuberculoma, so as to improve the understanding of
      this disease. METHODS: We retrospectively analyzed the clinical, laboratory,
      pathological and radiological data of 83 cases of pleural tuberculoma diagnosed
      by pathology and(or) bacteriology in Shanghai Pulmonary Hospital Affiliated to
      Tongji University. RESULTS: In the recruited 83 cases, there were 50 males and 33
      females, aged from 7 to 85 years old, with a mean age of 37.8 years. Cough, fever
      and chest pain were common symptoms, but no significant symptoms were seen in 25
      patients (31.3%). Some patients had positive physical signs, such as dullness to
      percussion and low breath sound. Pulmonary tuberculosis was also present in 36
      patients (43.3%) with pleural tuberculoma. A history of tuberculous pleurisy was
      elicited in 80 patients, among whom 45 (56.3%) received delayed antituberculous
      treatment and 42 (52.5%) received nonstandard treatment. Forty-eight cases
      (60.0%) did not receive corticosteroids. Fifty-nine cases underwent CT-guided
      percutaneous biopsy, while 24 underwent thoracoscopic surgery, and tuberculosis
      was pathologically confirmed in 62 (74.7%). Pathological profiles included
      granuloma, coagulation or caseation necrosis, lymphocyte infiltration,
      epithelioid cells, inflammatory cells, histiocytes and scar tissue. Fifteen
      (18.1%) specimens from percutaneous biopsy were anti-fast smear positive, while
      Mycobacterium tuberculosis was obtained by culture in 21 (25.3%) cases. Chest X
      ray showed that solitary lesions were seen in 68 cases, multiple foci in 15. The
      lesions of 46 cases (55.4%) occupied the lower right lobes. Round-like shadows
      were the most common signs, which were present in 63 cases (75.9%). CT
      examination demonstrated homogeneous density in 20, heterogeneous density in 40,
      calcification in 9, central attenuation in 34, and peripheral intensification in
      28 cases. CONCLUSIONS: Pleural tuberculoma is an important sequelae of
      tuberculous pleurisy. Understanding its clinical, pathological and radiological
      characteristics is helpful for the differential diagnosis of pleural and lung
      diseases.

PMID- 19576039
TI  - [The effect of GST M1 and GST T1 gene mutations on anti-tuberculous drug induced
      hepatic injury].
AB  - OBJECTIVE: To study the relationship between the polymorphisms of GST M1 and GST
      T1 genes and anti-tuberculous drug induced hepatic injury (ADIH). METHODS: A 1:1
      matched case-control study was carried out. One hundred and six patients [age (49
      +/- 19) years, 73 men and 33 women] fulfilling the criteria of ADIH during the 3
      month follow-up after the initiation of anti-tuberculous therapy were included,
      while 106 cases [age (49 +/- 19) years, 73 men and 33 women] without any hepatic
      injury served as the controls. The genotypes of GST M1 and GST T1 genetic
      polymorphisms were detected by polymerase chain reaction (PCR) in patients who
      received anti-tuberculosis therapy. Using SPSS 11.5 for windows software,
      univariate and multivariate conditional logistic analyses were conducted for
      studying the relationship between the polymorphisms and ADIH. RESULTS: Univariate
      analysis demonstrated that the "null" genotype of GST M1 gene occurred in 50
      (47.2%) of the cases, more frequent than in the controls [25 (23.6%)], with a
      crude OR (95%CI) 2.786 (1.513 - 5.130). No significant association was observed
      between ADIH and GST T1 polymorphism. Among the risk factors analyzed, body mass
      index and alcohol drinking were significantly associated with ADIH. In the
      multivariate analysis, a significant association between ADIH and the "null"
      genotype of GST M1 existed, after adjusting for body mass index and drinking
      status, adjusted OR (95%CI) being 3.022 (1.540 - 5.926). Again, no significant
      association was observed between GST T1 polymorphism and ADIH. CONCLUSION: This
      study demonstrated that patients carrying GST M1-"null" genotype may be
      susceptible to ADIH.

PMID- 19576040
TI  - [An analysis of the survey data on Hangzhou community physicians' perceptions of
      asthma knowledge and management].
AB  - OBJECTIVE: To evaluate the basic knowledge of asthma, the standardization of
      treatment and the continuing education with community physicians in Hangzhou.
      METHODS: The survey investigated a total of 45 community health service centers
      in Hangzhou, and 2 - 4 western medicine physicians were randomly selected from
      each centre. A questionnaire was completed by totally 114 doctors under
      investigation. RESULTS: Eighty-seven percent of the physicians believed asthma
      was an airway inflammatory disease. Sixty-nine percent chose inhaled
      glucocorticoids as daily first-line drug for persistent asthma and 55% had read
      asthma guidelines. However, only 24% had ever heard China Asthma Alliance (CAA)
      and only 6% had visited its website. Moreover, no one under investigation had
      participated in the CAA organized talks popularizing the standardization of
      asthma treatment. Over the past year, 55% of the respondents did not participate
      in any asthma-related meetings or seminars. Ninety-six percent of those surveyed
      expressed the hope that higher-level hospital doctors would come to the community
      hospital for asthma-related seminars. Among the 45 community health service
      centers, only 2 collected part of the registration data for asthma patients and
      only one conducted health education seminars for asthma patients during the past
      year. CONCLUSION: Community physicians need to be provided more continuing
      education opportunities in order for them to provide standard asthma treatment
      for patients.

PMID- 19576042
TI  - [Changes of the sodium channel in alveolar type II cells in pulmonary water
      transport in rats with oleic acid-induced acute lung injury].
AB  - OBJECTIVE: To determine the capability of alveolar fluid clearance and the
      changes of sodium channel in alveolar type II cells (ATII) in oleic acid-induced
      acute lung injury. METHODS: Forty four male Sprague-Dawley (SD) rats were
      randomized into a control group and an acute lung injury (ALI) group, with 22
      rats in each group. The ALI model was established by oleic acid. The ATII cells
      were acutely isolated and purified, and the ATII cellular ultrastructure was
      observed by transmission electron microscope. In each group, the mRNA expression
      of 3 epithelial sodium channel (ENaC) subunits in acute isolated ATII cells from
      8 rats were detected by reverse transcription-polymerase chain reaction (RT-PCR),
      while the extravascular lung water (EVLW) content was quantified in 7 rats by
      gravimetric measurement, and the lung histopathological changes were studies in 7
      rats. RESULTS: In the ALI group, Smith lung injury score (7.6 +/- 0.8) and EVLW
      (0.80 +/- 0.17) ml were significantly higher than those in the control group
      [Smith score: (1.1 +/- 0.2), t = -20.859, P < 0.01; EVLW: (0.52 +/- 0.10) ml, t =
      -3.851, P < 0.01]. The transmission electron microscopic observation showed that
      there were degeneration, apoptosis, and lamellar body vacuolar changes in the
      ATII cells from the ALI rats. RT-PCR demonstrated that the alpha-subunit of the
      ENaC mRNA expression was the highest among the 3 subunits (F = 4.40, P = 0.02).
      In the ALI group, mRNA expressions of all the 3 ENaC subunits in acutely isolated
      ATII cells were decreased as compared to those in the control group [alpha
      subunit: (51 +/- 9)% vs (82 +/- 7)%, t = 7.61, P < 0.01; beta-subunit: (13 +/-
      7)% vs (25 +/- 4)%, t = 4.53, P < 0.01; gamma-subunit: (31 +/- 15)% vs (40 +/-
      17)%, t = 3.01, P < 0.05; respectively]. CONCLUSIONS: The capacity of alveolar
      fluid clearance was attenuated in oleic acid-induced acute lung injury. The ENaC
      subunit mRNA levels of ATII cells were significantly decreased in ALI rats.

PMID- 19576041
TI  - [Transbronchoscopic balloon detection and selective bronchial occlusion for
      intractable pneumothorax].
AB  - OBJECTIVE: To evaluate the effect, complications and safety of transbronchoscopic
      balloon detection (TBD) and selective bronchus occlusion (SBO) for intractable
      pneumothorax. METHODS: Forty cases of pneumothorax from 5 teaching hospitals in
      Fujian province were included for this study. TBD was performed in all the 40
      cases for whom chest tube drainage had lasted for more than 7days but failed to
      close the pleura fistulae. Bronchi leading to pleura fistulae (the target
      bronchus) were detected by balloon-catheter (Olympus B7-2C) through bronchoscope.
      After the target bronchus was located, SBO procedures were performed. Autologous
      blood (20 ml to 30 ml) was injected into the target bronchus and followed by
      thrombin solution (1000 U) through balloon-catheter. In 10 cases, oxygenation and
      pulse rate were recorded by pulse-oximeter (Healthdyne 920M) during TBD and SBO.
      Another 10 cases undergoing bronchoscope without performing TBD and SBO served as
      the controls. Thorax CT, white blood cell count, neutrophil count and body
      temperature were measured after SBO. RESULTS: Bronchi leading to pleura fistulae
      were located by TBD in 34 out of the 40 cases. Air leakage was stopped after the
      first occlusion in 30 cases, but 5 of which underwent a second occlusion because
      of recurrence in 72 h. Of the 5 cases, air leakage was stopped in 3, and surgery
      was required in 2. Taken together, 28 of the 34 cases were cured by SBO and 6
      failed. There were no statistically differences between the treatment group and
      the control group in oxygenation changes during TBD and SBO procedures. In 10
      cases thorax CT scan was followed up in 7 days after SBO, and no obstructive
      atelectasis was found. In 20 cases peripheral white blood cell count was followed
      up 72 hours after SBO. Leukocytosis (> 10.0 x 10(9)/L) was found in 3, in which
      pulmonary infection was diagnosed, and leukocytosis was present in 2 cases before
      the procedure. Five patients (5/34) experienced mild to moderate fever, which
      resolved quickly. CONCLUSION: TBD/SBO are safe and effective procedures for
      intractable pneumothorax.

PMID- 19576043
TI  - [Effect of peroxisome proliferators activated receptor gamma and its ligand on
      airway mucus hypersecretion in rats].
AB  - OBJECTIVE: To explore the effect and the molecular mechanisms of peroxisome
      proliferators activated receptor gamma (PPAR-gamma) and its ligand on airway
      mucus hypersecretion. METHODS: Thirty-six Sprague-Dawley rats were randomized
      into the following groups: (1) Rats in the saline control group (n = 6) received
      normal saline inhalation; (2) Rats in the rosiglitazone control group (n = 6)
      received inhaled saline and oral rosiglitazone 8 mg/kg simultaneously; (3) Rats
      in the acrolein group (n = 6) received inhaled acronine 3.0 mg/L, 6 h/day, for 12
      days; (4) Rats in the rosiglitazone intervention group (n = 18) received inhaled
      acrolein and oral rosiglitazone 2 mg/kg, 4 mg/kg, 8 mg/kg, respectively, as the
      low dose, the moderate dose and the high dose intervention groups (n = 6 each).
      The lung tissue sections were stained with HE for histopathological examination.
      The changes of airway mucus were examined with AB-PAS. Expressions of MUC5AC and
      PPAR-gamma protein in the bronchial epithelium were detected by
      immunohistochemistry. The expression of mRNA was measured with real time RT-PCR.
      The data were analyzed with SPSS 10.0 software. Variables were compared with One
      Way ANOVA and q test. The correlations between variables were analyzed using
      Pearson's correlation coefficient. RESULTS: The levels of airway mucus were (60.2
      +/- 9.3)%, (4.9 +/- 1.0)%, (53.3 +/- 8.5)%, (26.5 +/- 7.4)%, (12.5 +/- 3.7)%
      respectively in the acrolein group, the saline control group, the low dose
      rosiglitazone intervention group, the moderate dose rosiglitazone intervention
      group, and the high dose rosiglitazone intervention group, the difference being
      significant among groups (F = 93.80, P < 0.01). The protein expressions of MUC5AC
      in the bronchial epithelium examined by immunohistochemistry were 4339 +/- 453,
      1636 +/- 282, 3996 +/- 346, 3048 +/- 331, 2376 +/- 343 respectively in the
      acrolein group, the saline control group, the low dose rosiglitazone intervention
      group, the moderate dose rosiglitazone intervention group, and the high dose
      rosiglitazone intervention group, the difference being significant among groups
      (F = 67.74, P < 0.01). The protein expressions of PPAR-gamma were 1159 +/- 184,
      838 +/- 151, 1272 +/- 189, 1568 +/- 282, 1872 +/- 270 respectively in the
      acrolein group, the saline control group, the low dose rosiglitazone intervention
      group, the moderate dose rosiglitazone intervention group, and the high dose
      rosiglitazone intervention group, the difference being significant among groups
      (F = 21.53, P < 0.01). The mRNA expressions of MUC5AC (the relative copies) were
      35.3 +/- 10.0, 2.2 +/- 0.7, 30.5 +/- 10.2, 18.6 +/- 5.3, 10.8 +/- 2.6
      respectively in the acrolein group, the saline control group, the low dose
      rosiglitazone intervention group, the moderate dose rosiglitazone intervention
      group, and the high dose rosiglitazone intervention group, the difference being
      significant among groups (F = 29.67, P < 0.01). The mRNA expressions of PPAR
      gamma (the relative copies) were 7.8 +/- 1.9, 2.0 +/- 0.6, 9.8 +/- 2.8, 18.6 +/-
      5.3, 31.6 +/- 8.9 in the acrolein group, the saline control group, the low dose
      rosiglitazone intervention group, the moderate dose rosiglitazone intervention
      group, and the high dose rosiglitazone intervention group, the difference being
      significant among groups (F = 39.47, P < 0.01). The expression of MUC5AC mRNA was
      negatively correlated with the protein expression of PPAR-gamma in the acrolein
      group (r = -0.880, P < 0.01). CONCLUSIONS: PPAR-gamma was involved in airway
      mucus hypersecretion induced by acrolein. PPAR-gamma and its ligand rosiglitazone
      inhibited acrolein-induced airway mucus hypersecretion, possibly through
      downregulation of MUC5AC.

PMID- 19576044
TI  - [Overexpression of endothelin-1 induces hypertrophy of rat pulmonary arterial
      microvascular smooth muscle cells via Akt/mTOR pathway].
AB  - OBJECTIVE: To investigate the effects of endothelin-1 (ET-1) overexpression on
      hypertrophy of the rat pulmonary arterial microvascular smooth muscle cells
      (RPMCs) in vitro. METHODS: Lung tissue perfusion method was used to obtain the
      primary RPMCs, and then the cells were transiently transfected with ET-1 plasmids
      or empty vectors via Lipofectamine. Flow cytometry was used to determine the
      distributions of the cell cycle and cell size of RPMCs. Immunofluorescence
      staining and Western blotting were used to determine the level of alpha-smooth
      muscle actin. The ratio of the protein/DNA of the transfected RPMCs was also
      calculated. Western blotting was used to examine the levels of phosphorylations
      of protein kinase B/Akt, mTOR, and ERK1/2. RESULTS: Primary RPMCs were isolated
      successfully. Overexpression of ET-1 resulted in a significant increase in total
      protein synthesis, expression of alpha-SMA, as well as increased cell size.
      Western blotting results showed that overexpression of ET-1 resulted in increased
      phosphorylation of Akt, mTOR and a decreased phosphorylation of ERK1/2 in RPMC.
      CONCLUSIONS: ET-1 overexpression induces RPMC hypertrophy and activation of
      Akt/PKB-mTOR pathway may be involved in the mechanism, with important
      implications for the pathogenesis of vascular remodeling in pulmonary arterial
      hypertension.

PMID- 19576045
TI  - [Corticosteroids in chronic obstructive pulmonary disease: past, present and
      future].

PMID- 19576046
TI  - [Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease].

PMID- 19576058
TI  - [Urgent action needed to raise public awareness of age-related macular
      degeneration in China].
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      developed countries. The impact of AMD to the economics, society and the patients
      are huge. However, the awareness of AMD is alarmingly low. Even in developed
      countries, the awareness of AMD is below 30%. In terms of the risk factors of
      AMD, the awareness is also quite low, e.g., only 32% were aware of the causal
      link between smoking and AMD. Although cataract is the leading cause of the
      blindness in China, as the economic and social progress, as the coming of the
      aging society, as people pursuing higher quality of life, AMD will become a
      unignoring public health problem. Thus, it is urgent to take action now to
      increase the public awareness of AMD.

PMID- 19576057
TI  - [Emphasizes the research of diabetic retinal neurons lesions and retinal
      neuroprotection].
AB  - Diabetic retinopathy includes retinal microangiopathy and retinal neuronopathy.
      Most of the clinical research has been primarily focused on the former. The
      retinal microvascular lesions and its complications has standardized in diagnosis
      and treatment. However, the emphasis on the latter has not been attached to the
      importance in clinic, and it has fewer studies on it. In recent years, studies
      have shown that the functional lesion of the retinal neurons and glial cells
      often can be detected earlier than microangiopathy in diabetic patients.
      Therefore, emphasis on the research of the diabetic retinal neurons lesions and
      retinal neuroprotection is beneficial to understand the essence of diabetic
      retinopathy rightly, and has great practical significance in preventing and
      reversing diabetic retinal neuronopathy in the early stage.

PMID- 19576059
TI  - [Characteristics of age-related macular degeneration in Chinese population].
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      elderly population and threatens the ability of patients to live independently.
      Ethnic differences are evident in the prevalence of AMD, its clinical features,
      as well as treatment responses to photodynamic therapy (PDT), most likely due to
      the differences in genetic backgrounds, disease susceptibility, living
      environments and habits. This article reviewed ethnic/racial differences in AMD,
      paying particular attention to the Chinese population, and highlighted the key
      findings. Compared to Caucasians, the prevalence of early and late stages of AMD
      is relatively lower and the polypoidal choroidal vasculopathy (PCV) is more
      commonly seen in the Chinese population. Regarding genetic susceptibility, the
      complement factor H (CFH) Y402H variant is not associated with exudative AMD in
      Chinese although it is strongly associated with AMD in Caucasians. In addition,
      visual outcome in Chinese patients with AMD seems to be better than that in
      Caucasian patients after PDT at 1 year follow-up.

PMID- 19576060
TI  - [Outcome of pars plana vitrectomy on idiopathic macular hole].
AB  - OBJECTIVE: To assess the efficacy in patients undergoing pars plana vitrectomy
      for the treatment of idiopathic macular hole (IMH). METHODS: Retrospective
      observational case series. Retrospective analysis of vitrectomy for IMH patients
      treated between January 2001 and January 2008 was performed. The statistical
      software SPSS10.0 were used to analyze the data such as surgical technique,
      closure rate, BCVA, hole size and stage etc. The variables in normal distribution
      were compared by independent sample t-tests, the qualitative data were compared
      by R x C table, and the ordered data were compared by nonparametric tests.
      RESULTS: Fifty eight eyes of 57 patients underwent vitrectomy with gas (10%
      C(3)F(8)) injection. Primary closure was achieved in 44 eyes (75.9%) with an
      average hole size of 0.20 mm(2) (0.01 - 0.85 mm(2)), whereas the size in the
      remaining 14 eyes was 0.69 mm(2) (0.08 - 3.16 mm(2)). The closure rate of the 36
      eyes treated with ILM peeling was 80.6% (29/36), and decreased visual acuity was
      not observed in 72.2% of them (26/36). The closure rate of the 22 eyes without
      ILM peeling was 68.2% (15/22), and decreased visual acuity was not observed in
      59.1% of them (13/22). There was a significant difference in the size and the
      change of BCVA between the closed cases and the unclosed cases, and no other
      factors had significant effect on the BCVA. CONCLUSIONS: Vitrectomy was evaluated
      as an useful treatment for IMH. ILM peeling in vitrectomy could not improve the
      closure rate and the visual outcomes. Preoperative hole size may be a sensitive
      predictor for postoperative closure.

PMID- 19576061
TI  - [Scleral buckling combined with intravitreal gas injection for treatment of
      retinal detachment in vitrectomized eyes without silicon oil tamponade].
AB  - OBJECTIVE: To evaluate the effects of scleral buckling combined with intravitreal
      gas injection for the treatment of retinal detachment in selected eyes which had
      undergone vitrectomy but without silicon oil tamponade. METHODS: This was a
      retrospective observational case series. Including 52 eyes of 52 selected
      patients. All patients had undergone vitrectomy without silicon oil tamponade as
      the first surgery for the treatment of various vitreoretinal diseases. After the
      failure of the first surgery, scleral buckling combined with intravitreal gas
      injection were performed for the treatment of retinal detachment in Xijing
      Hospital between January 2001 and May 2004. The scleral buckling was used in all
      surgeries and using radial placement of a silicon sponge or circumferential
      placement of solid silicon combined with an encircling band. During the surgery,
      all breaks were carefully marked to ensure they were on the crest or anterior
      slope of the buckle. Air or C(3)F(8) gas was injected intravitreously. The
      reattachment rate, visual outcome, and postoperative complications were
      investigated. RESULT: After a six-month to three-year follow-up period, the
      reattachment rate was 69.2% (36/52 cases). Further vitrectomy surgeries were
      needed for other 16 eyes. The visual acuity was improved in 32 eyes (61.5%),
      three eyes (23.1%) with no change, and 8 eyes (15.4%) decreased. Macular
      epiretinal membrane happened postoperatively in one eye, and cataract was found
      in another case. There is no serious complications. CONCLUSIONS: Scleral buckling
      combined with intravitreal gas injection is an effective procedure for the
      treatment of retinal detachment in vitrectomized eyes without silicon oil
      tamponade. The rate of secondary vitrectomy also can be reduced.

PMID- 19576062
TI  - [Clinical characteristics of suspected combined hamartoma of the retina and
      retinal pigment epithelium].
AB  - OBJECTIVE: To analyze the clinical presentations, and explore the diagnosis, and
      differential diagnosis of combined hamartomas of the retina and retinal pigment
      epithelium (CHRRPE). METHODS: A retrospective review of five patients with
      suspected CHRRPE presented to Peking Union Medical College Hospital, Chinese
      Academy of Medical Sciences & Peking Union Medical College, from Nov 2001 to July
      2008. The clinical presentations, fundus characteristics, fundus fluorescein
      angiography (FFA), optic coherence tomography (OCT), as well as B ultrasound scan
      examinations were analyzed. RESULTS: The five patients were all male, ranging in
      age from 6 to 18 years (mean 12 years). The lesion was unilateral; there were not
      any associated diseases. Presenting symptoms included painless decrease in
      vision, metamorphopsia, and discovery of strabismus. Initial visual acuity ranged
      from 20/333 to 20/50. Locations of the lesion included on optic disk and adjacent
      retina, and in the macular area. Clinical characteristics were slight elevation
      on optic disk or in retina, different degree of hyperpigmentation, retinal
      vascular tortuosity, as well as epiretinal membrane formation. In arterial phase
      of FFA, there was hypofluorescence of choroid background, retinal vascular was
      tortuous and telangiectatic, and there was leakage from vessels within the lesion
      in venous phase and late phase. OCT showed obscuration of the normal retinal
      layers, elevated lesion with high reflectivity of the inner retina, and
      hyporeflective shadowing of the underlying tissue. B ultrasound scan showed
      slightly elevated solid mass involving the disc or adjacent retina in some
      patients. CONCLUSIONS: CHRRPE may be confused with other masses of the retina and
      choroid. Diagnosis of CHRRPE mainly depends on fundus manifestations, FFA and
      OCT. B ultrasound scan is useful for differential diagnosis.

PMID- 19576063
TI  - [Experimental study on anatomy of adjacent structures of the optic canal].
AB  - OBJECTIVE: To provide microanatomical data for optic canal decompression surgery
      or paranasal sinus surgery through anatomical study on adjacent structures of the
      optic canal. METHODS: It was a experimental study. (1) Fifty dry cadaveric adult
      heads (100 sides) were dissected. The shapes and sizes of ethmoid sinus and
      sphenoid sinus were observed and measured. (2) The distance between the mid-point
      of the lateral wall of the sphenoid sinus and the internal carotid artery, the
      angle between the initial section of the ophthalmic artery and internal carotid
      artery were observed and measured under both naked eye and microscope. The
      distance between the medial margin of bilateral optic nerve at the frontal outlet
      were measured on 15 formalin-fixed wet cadaveric adult heads. The relationships
      between the optic canal and ethmoid sinus and sphenoid sinus were observed on 6
      formalin-fixed cadaveric adult heads by CT scanning; the morphological features
      and adjacent structures were contrasted and observed on 6 ice-frozen cadaveric
      head specimens by CT scanning and corresponding applied sectional anatomy.
      RESULTS: The anterior-posterior diameter of total ethmoid sinus was (39.02 +/-
      4.89) mm. The horizontal diameter of anterior ethmoid sinus was (12.26 +/- 2.12)
      mm. The superior-inferior diameter of anterior ethmoid sinus was (11.89 +/- 2.56)
      mm. The anterior-posterior diameter of sphenoid sinus was (24.08 +/- 4.87) mm.
      The distance between the middle part of the lateral wall of sphenoid sinus and
      internal carotid artery was (1.23 +/- 0.56) mm; the angle between the initial
      section of ophthalmic artery and internal carotid artery was 54.33 degrees +/-
      7.89 degrees . The distance between the medial margin of bilateral optic nerve at
      the frontal outlet was (14.26 +/- 3.23) mm. CONCLUSIONS: (1) When the medial wall
      of the optic canal is opened inside the sphenoid sinus, the depth shouldn't
      exceed 13 mm, otherwise it may damage the internal carotid artery and cause
      severe bleeding even death. (2) The depth should be less than 15 mm and the
      superior-inferior diameter should be less than 12 mm inside the anterior ethmoid
      sinus, otherwise the opposite ethmoid sinus or frontal base may be opened
      accidently. (3) The ophthalmic artery should be specifically protected in order
      not to cause ocular ischemia and blindness.

PMID- 19576064
TI  - [Pharmacologic vitreolysis in diabetic rats].
AB  - OBJECTIVE: To evaluate the efficacy and safety of plasmin or hyaluronidase in the
      inducing of posterior vitreous detachment in diabetic rats. METHODS: Forty SD
      rats were induced diabetes by Streptozotocin (STZ). Four weeks later, these rats
      were randomized into 4 groups: rats in group A received 5 U hyaluronidase
      intravitreal injection in right eyes; rats in group B received 0.5 U plasmin
      intravitreal injection in right eyes; rats in group C received 0.5 U plasmin +5 U
      hyaluronidase intravitreal injection in right eyes; rats in group D received BSS
      (balance salt solution) 2 microl intravitreal injection in right eyes. Clinical
      examination were performed at 1, 3, 7 days after injection. After 1 week,
      scanning electron microscope (SEM) was performed to judge whether the PVD was
      induced. ERG and histology were examined to evaluate the toxicity after the
      intravitreal injection of these two drugs. RESULTS: No PVD was found in SEM
      disclosed group A and group D. Forty percent eyes were induced complete PVD in
      groups B, and one hundred percent eyes were induced complete PVD in group C. ERG
      and histology showed no toxicity changes in any group. CONCLUSION: Intravitreal
      injection of 0.5 U plasmin + 5 U hyaluronidase can induce complete PVD without
      obvious toxicity in diabetic rats. Solo usage of plasmin or hyaluronidase can not
      induce complete PVD.

PMID- 19576065
TI  - [The clinical investigation of dynamic changes of corneal astigmatism and visual
      quality for patients after phacoemulsification surgery through different incision
      and implantation of different designed intraocular lens].
AB  - OBJECTIVE: To compare the corneal astigmatism and wavefront aberration
      differences of patients with cataract coexisting corneal astigmatism after
      phacoemulsification surgery through traditional superior clear corneal incision
      or phacoemulsification surgery through clear corneal incision guided by corneal
      topography and implantation of different spherical aberration intraocular lenses
      (IOL). METHODS: In a prospective randomized sample controlled clinical trial, 90
      patients (90 eyes) with age-related cataract and corneal astigmatism were
      randomly divided into 3 groups: (Group A) traditional superior corneal incision
      phacoemulsification surgery and AcrySof SN60AT IOL implantation, (Group B)
      corneal topography guiding incision phacoemulsification surgery and AcrySof
      SN60AT IOL implantation and (Group C) corneal topography guiding incision
      phacoemulsification surgery and AcrySof SN60WF IOL implantation. Corneal
      topography tests were performed at 1 week, 1 month, 3 months and 6 months
      postoperatively. The Wavefront aberration was measured using a custom built
      Tscherning wavefront sensor-ALLEGRETTO WAVE Analyze at 90 days postoperatively.
      Third-, 4th-, 5th-, total and higher-order aberration (HOA) root-mean-square
      (RMS), spherical aberration and coma aberration were compared at virtual pupil
      diameters of 6 mm postoperatively. Statistical analyses were performed using the
      analysis of chi square test, repeated measurement data analysis of variance, one
      way analysis of variance (ANOVA), and multiple comparisons Students-Newman-Keuls
      test. RESULTS: Corneal topography tests indicated that no significant difference
      for corneal astigmatism was found between these three groups preoperatively (F =
      0.08, P > 0.05). The corneal astigmatism was decomposed into J(0), J(45) and P
      with a Vector-based method, and statistically analyzed. When compared with Group
      B and GroupC, Group A had higher values of corneal J(0) (F = 9.54, P < 0.01) and
      P (F = 18.69, P < 0.01). For corneal J(0) and P, no significant difference was
      found between Group B and Group C (P > 0.05). However groups and times had
      interactions (F = 13.45, 50.22, P < 0.01, respectively). For astigmatic vectors,
      there were statistical significances between different times in 3 groups (F =
      74.33, 92.11, P < 0.01, respectively). Wavefront aberration test results
      indicated that the mean values of RMSg (root mean square of general aberration),
      coma aberration, RMSh, RMS(3), RMS(5) and RMS(6) of Group A were obviously higher
      than that of Group B and C (F = 93.40, 471.94, 176.95, 216.99, 44.37, 37.19, P <
      0.01, respectively). And the values of RMS(4) and spherical aberration in Group A
      were significantly higher than that in Group C (q = 25.30, 26.23, P < 0.01,
      respectively). No statistically significant was found between Group A and Group B
      of RMS(4) and spherical aberration (q = 0.57, 2.34, P > 0.05, respectively). The
      values of RMS(4), RMSh, RMSg and spherical aberration in Group B were
      statistically significantly higher than that in Group C (q = 24.73, 7.90, 6.41,
      23.89, P < 0.01, respectively). CONCLUSIONS: Corneal topography guiding incision
      phacoemulsification surgery and the implantation of negative spherical aberration
      IOL is a more favorable solution for cataract patients coexisting corneal
      astigmatism, which can correct the corneal astigmatism, decrease the spherical
      aberration, high-order aberration and general aberration of pseudophakic eyes and
      therefore improve the visual quality of patients.

PMID- 19576066
TI  - [Preliminary clinical study of Descemet's stripping with endothelial keratoplasty
      for bullous keratopathy].
AB  - OBJECTIVE: To investigate the indications, surgical procedure, clinical efficacy,
      and the prevention and management of complications of Descemet's stripping with
      endothelial keratoplasty (DSEK) for bullous keratopathy. METHODS: In the
      nonrandomized retrospective consecutive case series, 8 patients (8 eyes) with
      bullous keratopathy at Zhongshan Ophthalmic Center between September 2006 and
      October 2007 underwent DSEK surgery. During the surgical procedure, the
      Descemet's membrane and abnormal endothelial layer were stripped from the central
      recipient posterior surface with 7.75 mm diameter, and then a specially designed
      scraper was used to roughen the peripheral recipient posterior stroma. Other
      surgical techniques were the same with routine DSEK surgery. The adherence of the
      donor lenticule to the recipient posterior stroma and postoperative donor
      lenticule dislocation were monitored in the early stage after surgery. Best
      spectacle-corrected visual acuity (BSCVA), graft clearance, corneal astigmatism
      and endothelial cell density (ECD) were observed over a 3-9 months follow-up
      period. RESULTS: All donor lenticules were well adherent to the recipient
      posterior stroma and no graft dislocation occurred postoperatively. One patient
      had papillary block glaucoma at 1-day, and relieved after 48 hours postoperative.
      All grafts remained transparent, and had improved visual acuity. BSCVA was 0.3 -
      0.7 postoperative. Six patients with preoperative pain had been pain free after
      DSEK procedure. Mean corneal astigmatism was (1.90 +/- 0.70) diopter (D). Mean
      ECD was (2014 +/- 192) cells/mm(2). CONCLUSIONS: Compared with deep lamellar
      endothelial keratoplasty (DLEK), DSEK procedure is technically easier and less
      traumatic to recipient cornea and anterior chamber structures. The skill of
      roughening the peripheral recipient posterior stroma should prevent postoperative
      graft dislocation effectively.

PMID- 19576067
TI  - [Preliminary observations of embolization treatment of orbital varices with
      Glubran 2 acrylic glue].
AB  - OBJECTIVE: To evaluate the outcome of embolization via orbital surgical exposure
      for a series of orbital varices. METHODS: This study is a retrospective review of
      28 patients (28 eyes, 11 men, 17 women) which were diagnosed as orbital varix
      from March to December in 2007, in the Institute of Orbital Diseases. Patient's
      age ranged from 11 to 54 years old, mean 32 years old. Right orbit 18 cases, left
      orbit 10 cases. All patients is under general anesthesia, operative approach
      included lateral orbitotomy (9 cases), anterior orbitotomy (11 cases),
      transconjunctival (7 cases) and percutaneous puncture (1 case). During the
      operation, venous malformations were dilatated and punctured with an 20-gauge
      catheter needle, then injected into 33% Glubran 2 with several punctures with
      different orientations of the needle were required to reach the different lobules
      of the venous pouch. RESULTS: Proptosis, visual acuity and eye movement for pre-
      and post-treatment were observed. All the patients treated with 100% efficiency,
      in which 16 cases (57%) were complete resolution of the signs and symptoms, no
      proptosis with Valsalva and correct completely or partially enophthalmos, 12
      cases (43%) marked resolution. Six patients partial resection as lesion was
      stiffen after glue injection, and can touch in anterior part of the orbit.
      Complications included the vision acuity loss (1 case), limitation of ocular
      movement (3 cases), and proptosis (2 cases). CONCLUSION: The embolization with
      Glubran 2 after direct surgical exposure is the safe and effective treatment for
      orbital varix and can correct some enophthalmos.

PMID- 19576068
TI  - [Clinical features and therapy of benign lymphoepithelial lesion].
AB  - OBJECTIVE: To report the clinical features of benign lymphoepithelial lesion and
      to further characterize recommendations for its therapy strategy. METHODS: It was
      a retrospective case sires. Retrospective analyze the clinical characteristics,
      imaging features, pathological manifestation and the treatment effect from the
      clinical materials of 9 cases of patients with benign lymphoepithelial lesion
      presenting to Tianjin Eye Hospital from Jan 2006 to Dec 2007. RESULTS: The 9
      cases, in which 7 cases were female, 7 cases had lesions on both eyes,
      demonstrated unpainful swelling of the lacrimal glands and in different degree of
      salivary glands or had history of tumor resection of salivary glands. Orbital CT
      scanning showed increased homogeneous density with clear boundary in the lacrimal
      gland area. Color doppler ultrasonography displayed elliptical space occupying
      with clear boundary and homogeneous internal echos of the lacrimal gland area.
      Six patients received treatment with large dose of glucocorticoid for 1 - 2
      courses, and the symptoms and signs were significantly alleviated. Three patients
      were operated to excise the lacrimal gland masses due to imperfect treatment
      effect of medication or in order to make definite diagnosis. The postoperative
      pathological results supported the diagnosis of benign lymphoepithelial lesion.
      No recurrence happened in the follow-up. CONCLUSIONS: A clinical condition with
      swelling of either or both lacrimal gland and of any salivary gland, and
      accompanied with systemic relative diseases should be considered benign
      lymphoepithelial lesion. Imaging examinations are helpful to definite diagnosis.
      Most patients are sensitive to the glucocorticoid treatment. The dose of
      glucocorticoid should be large at the beginning of treatment. Surgical excision
      can be applied to the cases insensitive to medications or difficult to be
      diagnosed. The definite diagnosis should be made through pathological
      examinations.

PMID- 19576069
TI  - [Effects of mutant kringle 5 eye drops on the survival time of corneal allografts
      in rat].
AB  - OBJECTIVE: To investigate the preventative effect of mutant kringle 5 (mK5) eye
      drops on corneal allograft rejection. METHODS: It was a experimental study. The
      outbred strain F344 and Lewis rats were used as donors and recipients
      respectively. Sixty Lewis rats were randomly divided into B, C, D and E Group;
      Group A, F344 rats autograft control; Group B, allograft control (the control
      groups were given normal sodium only); Group C and D, allograft groups, were
      treated with 5 mg/L and 10 mg/L mK5 eye drops respectively; Group E, allograft
      group, was treated with 0.1% dexamethasone eye drops. The eye drops were applied
      one drop four times per day for two weeks, the occurrence and development of
      corneal allograft rejection and corneal neovascularization (CNV) was observed
      every other day by slit-lamp microscope, the grafts were evaluated clinically by
      means of Holland's scoring system and the area of CNV was calculated. Nine rats
      per group were killed on the 14th day, and the corneas were taken for
      histopathological examinations. Analysis of variance was used to analyze the
      outcomes. RESULTS: The average graft survival time of Group B, C, D and E was
      (9.3 +/- 2.1), (21.1 +/- 7.3), (23.5 +/- 10.8) and (28.2 +/- 19.1) d
      respectively, Compared with Group B, Group C and D had a statistically
      significant prolongation of survival time (q = 10.24, 13.47; P < 0.05). Though
      treated with 0.1% dexamethasone eye drops (Group E) prolonged transplant survival
      time as compared with mK5 eye drops, but the difference was not statistically
      significant (q = 2.54, 1.49; P > 0.05). The occurrence of CNV in Group A was (3.1
      +/- 0.8) d, Group B (2.6 +/- 0.5) d, Group C (6.4 +/- 0.5) d, Group D (7.8 +/-
      0.7) d and Group E (5.3 +/- 1.0) d. Significant difference (q = 31.58, 51.21,
      19.98; P < 0.05) was found between groups C, D, E and Group A. There were also
      significant difference between groups C, D, E and Group B (q = 43.87, 67.14,
      24.53; P < 0.05). The CNV areas of Group C and Group D were also smaller than
      Group B (q = 30.76, 62.14; P < 0.05). The results was similar compared with Group
      E (q = 15.20, 25.64; P < 0.05). Fewer inflammatory cells and CNV were found in
      the cornea of the groups treated with mK5 eye drops. CONCLUSION: Topical
      application of mK5 eye drops can prevent corneal graft rejection and corneal
      neovascularization in rats.

PMID- 19576070
TI  - [Analysis on the susceptibility of fusidic acid for common gram positive
      bacteria].
AB  - OBJECTIVE: To assess in vitro susceptibility of the fusidic acid, vancomycin,
      tobramycin and ofloxacin for 8 kinds of ocular gram-positive bacteria. METHODS:
      It was an experimental study. One hundred strains of ocular gram-positive
      bacterial isolates selected from Beijing Institute of Ophthalmology, cultivated
      and identified by the routine, were tested for their susceptibilities to fusidic
      acid, vancomycin, tobramycin and ofloxacin, with in vitro by the Kirby-Bauer disk
      diffusion method. Significant differences between groups were evaluated by SPSS
      11.5 chi-square test of four-fold table. RESULTS: In the study, the percentage of
      susceptibility for in vitro gram-positive bacterial isolates to tobramycin,
      ofloxacin, vancomycin and fusidic acid was 55.0%, 65.0%, 98.0% and 53.0%. The
      susceptibility to vancomycin was significantly higher than to tobramycin,
      ofloxacin and fusidic acid (chi(2) = 51.425, 36.113, 54.737; P < 0.05). The
      susceptibility of common staphylococci to fusidic acid (85.5%) was just lower
      than to vancomycin (100.0%) (chi(2) = 6.605, P < 0.05), but was significantly
      higher than to tobramycin (58.2%) and ofloxacin (54.5%) (chi(2) = 10.106, 12.511;
      P < 0.05). The susceptibility of common streptococcus to fusidic acid (0.0%) was
      lower than to vancomycin (100.0%) and ofloxacin (85.0%) (chi(2) = 40.000, 29.565;
      P < 0.05), but the susceptibility to fusidic acid and tobramycin (15.0%) were
      equivalent (chi(2) = 1.441, P > 0.05). The gram-positive bacilli and nocardia
      showed significantly lower susceptibility to fusidic acid (24.0%) than that to
      the other three antibiotics (tobramycin 80.0%, ofloxacin 72.0%, vancomycin 92.0%)
      (chi(2) = 23.727, 22.430, 11.538; P < 0.05). CONCLUSION: The in vitro
      susceptibility of fusidic acid to staphylococci is higher, while to streptococcus
      and gram-positive bacilli is obviously lower than other three kinds of
      antibiotics.

PMID- 19576076
TI  - [Research situation of acute retinal necrosis].
AB  - Acute retinal necrosis is an uncommon but devastating, potentially blinding
      ophthalmopathy characterized by acute uveitis, vitreitis, retinal arteritis and
      full-thickness retinal necrosis, frequently complicated by secondary retinal
      detachment and proliferative vitreoretinopathy in late stages. However, it
      usually cannot be diagnosed and treated promptly, with unfavorable prognosis for
      the lesions tend to a rapid circumferential progression in few days. This review
      summarizes the epidemiology, pathogenesis, clinical features, diagnosis,
      differential diagnosis and recent situation in the study of treatment of acute
      retinal necrosis.

PMID- 19576079
TI  - [Questions on diagnosis and treatment of peripheral T/NK cell lymphomas].

PMID- 19576080
TI  - [Attentions should be paid to the assessment and risk classification in adult
      acute lymphoblastic leukemia].

PMID- 19576081
TI  - [A clinical study of chromosome translocations in extranodal marginal zone
      lymphoma of mucosa-associated lymphoid tissue in Chinese patients].
AB  - OBJECTIVE: To investigate the genetic aberrations in extranodal marginal zone
      lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different
      sites of the body in Chinese patients. METHODS: Two hundred and seventeen
      paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with
      interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21;
      q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1
      and BCL6 gene involved chromosome translocations. RESULTS: These translocations
      were mutually exclusive and detected in 21% (46/217) of the cases, including t
      (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1%
      (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation
      in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18)
      (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from
      lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland
      (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22;
      q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18)
      (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68).
      BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and
      stomach (4%, 3/84). CONCLUSIONS: It is demonstrated that the four translocations
      occur with markedly variable frequencies in MALT lymphoma of different sites in
      Chinese patients. The distributions of these chromosome translocations in Chinese
      patients are slightly different from those reported in western patients.

PMID- 19576082
TI  - [ABVD chemotherapy scheme at day 1 and 8 for treatment of primary Hodgkin's
      lymphomas].
AB  - OBJECTIVE: To explore the effect of adriamycin, bleomycin, vincristine and
      dacarbazinum (ABVD) chemotherapy scheme executed at day 1 and day 8 for primary
      Hodgkin's lymphomas (HL). METHODS: 62 patients with primary HL in stages II - IV
      treated in our department from October 2005 to October 2006 were divided into
      group A and B at random with 31 patients in each group. The patients in group A
      received ABVD chemotherapy scheme executed at day 1 and day 8 for 6 - 8 cycles.
      The patients in group B received ABVD chemotherapy scheme executed at day 1 and
      day 15 for 6 - 8 cycles. The patients of the groups received radiotherapy by the
      same doctor after chemotherapy according to the patients condition and the
      radiotherapy regimens were not affected by the grouping. RESULTS: The complete
      remission rate (CR) in group A after chemotherapy was 90.3% (28/31); the one-year
      and two-year disease free survival (DFS) rates were 87.1% (27/31) and 80.0%
      (20/25) respectively. The CR rate in group B after chemotherapy was 83.9%
      (26/31); the one-year and two-year DFS rates were 80.6% (25/31) and 72.0% (18/25)
      respectively. The discrepancy of CR rates and the one-year and two-year DFS rates
      between the two groups was not significant (P > 0.05). The incidences of
      therapeutic side effects such as myocardial ischemia grade III - IV liver
      function impairment, pulmonary fibrosis and serious marrow inhibition between the
      two groups were not significant too (P > 0.05). Average chemotherapy period for
      the patients in group A was 159 days; it was 69 days shorter than that in group
      B. CONCLUSION: The CR rate, 1-year DFS rate and 2-year DFS rate of ABVD
      chemotherapy scheme executed at day 1 and 8 are similar to those of ABVD
      chemotherapy scheme executed at day 1 and 15 for primary HL in stages II - IV.
      The side-effects of chemotherapy between group A and B are similar too. The
      chemotherapy period in group A is shortened significantly.

PMID- 19576083
TI  - [Blastic plasmacytoid dendritic cell neoplasm: two cases report and review of
      literatures].
AB  - OBJECTIVE: To identify the clinical and pathological features of blastic
      plasmacytoid dendritic cell neoplasm (BPDC). METHODS: The characteristics of BPDC
      hematodermic neoplasm were discussed with a report of two new cases and review
      the literatures. RESULTS: Both patients presented with skin nodules and the
      tumors were CD(4)(+) and CD(56)(+). Lineage specific markers for B- and T-cell
      were negative and the tumors did not express myeloperoxidase. Systemic
      chemotherapy resulted in complete remission, but the disease relapsed quickly and
      were unresponsive to further chemotherapy. The patients died 26 months and 11
      months respectively after diagnosis. CONCLUSION: BPDC hematodermic neoplasm is a
      rare subtype of lymphoma with distinct clinicopathologic and immunophenotypic
      features. The disease often has a fulminant course with a poor prognosis. More
      recent studies suggest that there is a derivation from a plasmacytoid dendritic
      cell precursor.

PMID- 19576084
TI  - [Clinical analysis of 15 patients with Waldenstrom macroglobulinemia].
AB  - OBJECTIVE: To explore the clinical characteristics of Waldenstrom
      macroglobulinemia (WM) and enhance the level of diagnosis and treatment. METHOD:
      The data of 15 patients with WM in our hospital from November 1995 to October
      2007 were retrospectively analyzed. RESULTS: The median age was 68.5 (60 - 79)
      years, male/female = 2.75/1. Main clinical manifestations were fatigue, loss of
      weight, splenomegaly and lymphadenopathy. All the patients accepted the treatment
      of alkylating agents, purine nucleoside analogs, bortezomib or thalidomide
      respectively. The follow-up period for the patients was 4 months to 10 years and
      the median follow-up time was 82 months. CONCLUSION: WM may often be seen in old
      male patients with varied clinical manifestations. The primary treatment is
      chemotherapy, but the disease is incurable. Bortezomib and thalidomide may
      improve the therapeutic effect.

PMID- 19576086
TI  - [A 10 years review of the characteristics of in-hospital ventricular fibrillation
      victim in a single center].
AB  - OBJECTIVE: To study the factors influencing the outcome of patients suffering
      from in-hospital ventricular fibrillation (IHVF), as there have been few studies
      focusing on this topic. METHODS: Patients with IHVF collected in a single cardiac
      center were classified into a successful group and a failure group. Data relevant
      to the predicting factors of the two groups were compared. RESULTS: There were
      206 events in the analysis. The most common underlining disease was coronary
      artery disease (CAD), especially acute myocardial infarction (AMI). On multiple
      logistic regression analysis, it was shown that the independent predictors for
      failure of defibrillation were higher NYHA class (OR 1.7, 95% CI 1.3 - 2.2, P <
      0.001), higher blood potassium level (OR 2.9, 95% CI 1.9 - 4.3, P = 0.007) and
      adrenaline usage (OR 25.0, 95% CI 11.5 - 55.1, P < 0.001). In a AMI sub-group,
      56.9% of the IHVF events occurred within the first day of AMI, and the occurrence
      descended with time going on within 2 weeks. Before the occurrence of IHVF, the
      patients with right coronary artery as the infarction related artery (IRA) often
      suffered from (8/9, 88.9%) bradycardia (R-R interval > 1 s), but those with left
      anterior descending artery as IRA often showed (8/12, 66.7%) tachycardia (RR
      interval < 0.6 s). CONCLUSIONS: The common disease causing IHVF is CAD. The worse
      the heart function, the higher the rate of IHVF and the worse the prognosis. It
      IHVF not induced by hypokalemia and use of adrenaline in resuscitation predict
      lower successful defibrillation rate.

PMID- 19576085
TI  - [A survey of glucose and lipid metabolism and concomitant diseases among
      inpatients in Guangdong province].
AB  - OBJECTIVES: To investigate the epidemiological and clinical characteristics of
      dyslipidemia as well as its treatment and influence on accompanying diseases in
      impaired glucose status among inpatients. METHODS: A cross-sectional survey was
      conducted among the inpatients registered in ten university hospitals of
      Guangdong, China during the week before the Diabetes Day in 2004. The fasting
      blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and
      concomitant disorders of the first screen during the hospitalization period were
      recorded. Those who had FBG level from 5.6 to 6.9 mmol/L and not been previously
      diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTT). RESULTS:
      Of the 8753 inpatients investigated, 1067 cases had complete medical records (CMR
      case) including PDM cases and previously non-diagnosed diabetes ones with FBG >
      or = 5.6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels
      from 5.6 to 6.9 mmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM,
      21.7% was newly diagnosed diabetes mellitus (NDM), 29.1% had impaired glucose
      regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels
      in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05,
      respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those
      in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the
      diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate
      was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P < 0.05,
      respectively). Only 22.8% of the PDM inpatients underwent treatment of
      dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP
      III. BMI was higher and waistline longer in the PDM and NDM inpatients than those
      in the NGT cases (P < 0.05, respectively). Seventy-two point eight percent of the
      PDM inpatients was complicated with more than one type of vascular diseases. Nine
      point seven percent and 0.2% of the NDM inpatients were tormented by diabetic
      nephropathy and diabetic retinopathy respectively. CONCLUSIONS: More inpatients
      with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which
      included hypertriglyceridemia, hypo-high-density lipoproteinemia and metabolic
      syndrome. Concomitant vascular diseases were more frequently found in PDM
      inpatients than in the others. Some of the NDM and IGT inpatients were
      complicated with microvascular diseases.

PMID- 19576087
TI  - [The expression and significance of activator protein-1 and matrix
      metalloproteinases in the human heart post acute myocardial infarction].
AB  - OBJECTIVE: To investigate the expression and significance of activator protein-1
      (AP-1) and matrix metalloproteinases (MMPs) in acute myocardial infarction (AMI)
      subjects. METHODS: Immunohistochemical techniques were used to detect the subunit
      of AP-1 (c-Jun), MMP-2 and MMP-9 in human AMI and normal heart tissue and the
      expressions of c-Jun and MMPs were measured with computer image analysis system.
      RESULTS: (1) There were expressions of c-Jun, MMP-2 and MMP-9 in normal heart
      tissue, mainly in myocardial cells and cardiac fibroblasts, and their expressions
      in AMI myocardial tissues were all significantly higher than those in normal
      myocardial tissues (P < 0.05). (2) The level of MMP-9 expression was
      significantly and positively correlated with c-Jun in AMI heart tissue (r =
      0.773, P < 0.01). CONCLUSIONS: The expressions of AP-1 and MMPs increase in human
      myocardial infarction. These findings suggest that AP-1 transcription activation
      pathway and MMPs may play an important role in ventricular remodeling of
      myocardial infarction.

PMID- 19576088
TI  - [A study on the light microscopic measurement of intercellular space of squamous
      epithelium in lower-esophagus to diagnose gastroesophageal reflux disease].
AB  - OBJECTIVE: To evaluate the significance of dilated intercellular space (DIS) of
      squamous epithelium in lower-esophagus which was measured at light microscopy
      (LM) in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: This
      study was divided into two parts. The first part consists of 133 GERD patients
      with typical symptoms, including 75 erosive esophagitis (EE) and 58 non-erosive
      reflux disease (NERD); the second part consists of 25 healthy volunteers as
      control; ambulatory 24-hr esophageal pH monitoring, endoscopy and biopsies which
      were taken in lower esophagus were performed in all individuals. NERD patients
      with negative ambulatory 24-hr esophageal pH monitoring were undertaken PPI test.
      We selected 43 individuals randomly (4 control, 11 NERD and 28 EE) to measure the
      intercellular space diameter with LM and transmission electronic microscopy (TEM)
      simultaneously. All the samples were observed at immersion objective, taken
      pictures and make the scale at the same time; all the pictures were measured by
      the computer-assisted morphometry and in the samples for one case should be
      measured 100 points and then calculate the mean intercellular space diameter,
      while the TEM has the same procedures. RESULTS: A total of 158 individuals (90
      male, 68 female) were enrolled in this study. The mean intercellular space
      diameter with LM of the controls, the NERD and the EE patients were (0.61 +/-
      0.10) microm, (1.12 +/- 0.61) microm and (1.30 +/- 0.19) microm, respectively,
      with significant differences between the control and NERD group, the control and
      EE group, the EE and NERD group (P < 0.05); the mean intercellular space diameter
      with LM of EE subgroup of LA-A, LA-B, LA-C, LA-D were (1.31 +/- 0.23) microm,
      (1.27 +/- 0.17) microm, (1.31 +/- 0.14) microm, (1.33 +/- 0.11) microm,
      respectively, without significant differences among every two subgroups (P >
      0.05); NERD patients with positive and negative 24-hr ambulatory pH monitoring
      were 40 and 17 cases, and the mean intercellular space diameter with LM were
      (1.12 +/- 0.16) microm, (1.11 +/- 0.31) microm, respectively, without significant
      differences between them (P > 0.05); the cut-off value of mean intercellular
      space diameter with LM was 0.85 microm, if combination the clinical GERD symptom,
      endoscopy and 24-hr ambulatory pH monitoring as gold standard, its sensitivity
      was 95.5% and specificity was 100%; the intercellular space diameter of the
      controls, the NERD patients and the EE patients with TEM were (0.30 +/- 0.14)
      microm, (1.33 +/- 0.28) microm, (1.40 +/- 0.22) microm, respectively, with
      significant differences between the control and NERD group, the control and EE
      group (P < 0.05). It was significant correlation in intercellular space diameter
      between LM and TEM (r = 0.737, P = 0.000). CONCLUSIONS: The intercellular space
      diameter of squamous epithelium in lower esophagus of GERD patients can make
      quantitative study with LM. It is significant correlation with TEM. DIS with LM
      is one of sensitive, specific and objective marker of GERD.

PMID- 19576089
TI  - [The application of ABCD2 Score in evaluation of the prognosis in transient
      ischemic attack].
AB  - OBJECTIVE: To assess the incidence, types and risk factors of atherothrombotic
      events (AT) within 7 days after transient ischemic attack (TIA) with ABCD2 Score
      in Chinese patients. METHODS: With ABCD2 Score, we retrospectively reviewed the
      medical records of 198 TIA patients, which met the inclusion criteria of our
      study. They were divided into a low risk group (ABCD2 < or = 3) and a moderate
      high risk group (ABCD2 > or = 4) and the incidence, types and risk factors of AT
      within 7 days after TIA were evaluated and compared respectively with chi(2) test
      between the two groups. Statistic significance was considered as P < 0.05.
      RESULTS: The order of the frequency of accompanying diseases was hypertension
      68.18% (135/198), diabetes 23.74% (47/198), coronary artery disease 21.72%
      (43/198), ischemic stroke 15.66% (31/198) and hyperlipemia 12.63% (25/198). AT
      within 7 days after TIA was observed in 6.19% (6/97) of the patients in the low
      risk group, all of them were suffering from TIA recurrence. In the moderate-high
      risk group, 14.85% (15/101) of the patients experienced AT, including 2 cases of
      TIA recurrence, 10 cases of ischemic stroke, 1 case of both TIA recurrence and
      ischemic stroke, 1 case of angina pectoris and 1 case of myocardial infarction.
      There was no peripheral vascular disease or death from vascular disease.
      Incidence of AT within 7 days in the moderate-high risk group was significantly
      higher than that in the low risk group (51.70% vs 27.27%, P < 0.05). CONCLUSION:
      TIA patients with ABCD2 > or = 4 are at higher risk of AT within 7 days after TIA
      onset.

PMID- 19576090
TI  - [The value of serum procalcitonin in treatment of community acquired pneumonia in
      outpatient].
AB  - OBJECTIVE: To evaluate the value of serum procalcitonin (PCT) on antibiotic use
      in treatment of community acquired pneumonia (CAP) in outpatient. METHODS: From
      November 2006 to February 2008, a total of 127 patients with CAP in outpatient
      were randomly assigned into two groups: PCT group (n = 63) and control group (n =
      64). PCT levels of all patients were measured after study admission. On the base
      of similarly normal treatment, the control group received antibiotics according
      to the attending physicians and the PCT group were treated with antibiotics
      according to serum PCT levels: antibiotic treatment was applied with PCT level >
      or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical
      efficacy, rate of antibiotics use, duration courses and costs of antibiotics were
      observed. RESULTS: Clinical efficacy of the PCT group was similar with the
      control group (92.1% vs 87.5%, P > 0.05); rate and costs of antibiotics use was
      lower, antibiotic duration of the PCT group was shorter than that of the control
      group (P < 0.05, P < 0.001, P < 0.001). CONCLUSION: PCT could be used in
      treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic
      use, shorten antibiotic duration and lower costs of antibiotic.

PMID- 19576091
TI  - [In vitro activity of daptomycin and other antimicrobial agents against 499
      strains of gram-positive cocci causing bloodstream infection].
AB  - OBJECTIVE: To evaluate the in vitro activity of daptomycin, vancomycin,
      teicoplanin, tigecycline, ceftobiprole and linezolid against 499 strains of blood
      isolated gram-positive cocci. METHODS: Determination of the minimal inhibitory
      concentration (MICs) of daptomycin with microbrothdilution method and the MICs of
      other 9 antimicrobial agents with agar dilution method against 499 strains of
      blood-isolated gram positive cocci was carried out. The data was analyzed with
      WHONET 5.4 software. RESULTS: The susceptibility rates of staphylococci to
      daptomycin, tigecycline, linezolid, ceftobiprole, vancomycin and teicoplanin were
      100%. All staphylococcus strains were inhibited by daptomycin at a MIC of 1 mg/L.
      The MIC(50) and MIC(90) of daptomycin were both 0.5 mg/L against methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus
      coagulase-negative (MRSCoN). Among Enterococcus spp, the highest MIC of
      daptomycin was 4 mg/L. The MIC(50) and MIC(90) of daptomycin were both 2 mg/L
      against E.faecalis, whereas they were 2 mg/L and 4 mg/L against E.faecium. One
      strains of linezolid-resistant E.faecalis (MIC: 8 mg/L) was susceptible to
      daptomycin (MIC: 1 mg/L). Three strains of E.faecium carrying vanA gene with
      vancomycin MICs above 32 mg/L and teicoplanin MICs also 32 mg/L were susceptible
      to daptomycin, tigecycline and linezolid. The MIC range of daptomycin against
      Streptococcus pneumoniae and Streptococcus viridans was 0.032 - 0.25 mg/L and
      0.125 - 1.000 mg/L separately. CONCLUSIONS: Daptomycin has excellent in vitro
      activity against common gram-positive pathogens isolated from blood. It may be a
      good choice for clinicians to treat drug-resistant gram-positive cocci.

PMID- 19576092
TI  - [The role of galactomannan detection in the diagnosis of invasive pulmonary
      aspergillosis in critically ill patients].
AB  - OBJECTIVE: To evaluate the usefulness of serum galactomannan (GM) for the
      diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients.
      METHODS: Study was conducted between February 2007 and July 2008. Included
      patients on admission ICU who suffer from suspected IPA. GM test and culture were
      collected 2 weekly. Clinical feature, mycological evidence and optical density
      index (ODI) were noted. Clinically invasive fungal infection (IFI) were defined
      proven, probable and possible. The patients were classified into neutropenia, non
      neutropenia and treated with immunosuppressive agents, non-neutropenia and non
      immunosuppressive agents. To compared of the sensitivity and specificity of GM in
      different patients. RESULTS: 94 patients were included, 4 patients were proven,
      29 patients were probable, 34 patients were possible IFI, 27 patients were non
      IPA. The positive rate of the GM was 31.9% (30/94). The sensitivity and
      specificity of GM in proven cases and probable cases are 66.7% and 92.6%. GM
      assay tended to become positive earlier than the culture 2 - 10 (5.33 +/- 2.17)
      d. We found that differences in patient diagnosis and selection might account for
      the disparities seen for positive rate for the GM test. There was positive in
      three of the four patients with proven, the positive rate of GM was 65.5% for
      probable cases, for possible cases was 17.6%, for non-IPA cases was 7.4% (P =
      0.001). For patient with neutropenia, treated with immunosuppressive agents and
      without immunosuppressive agents, the positive rate of GM was 52.9% vs 41.7% vs
      34.6% (P = 0.015); the sensitivity was 80.0% vs 70.0% vs 53.8% (P = 0.011), the
      ODI was 1.365 (0.582 - 6.736) vs 1.123 (0.623 - 6.868) vs 0.554 (0.522 - 0.823),
      P = 0.005, respectively. CONCLUSION: These results show that GM test is useful
      for early diagnosis IPA in critically ill patients. Differences in patient
      selection and diagnosis might account for the disparities seen for positive rate
      and sensitivity for the GM test. It has been higher sensitivity and ODI in the
      patient treated by immunosuppressive agents.

PMID- 19576109
TI  - [To pay attention to neurological diseases related to thyroid gland risk
      factors].

PMID- 19576108
TI  - [The past and future of mitochondria medicine].

PMID- 19576110
TI  - [Thoughts on invasive intervention for atrial fibrillation].

PMID- 19576111
TI  - [Focus on fluoroquinolones safety].

PMID- 19576112
TI  - [A study on the expression of anti-mitochondrial antibody in the brain of
      patients with MELAS syndrome].
AB  - OBJECTIVE: To investigate the pathological changes and pathogenesis of the MELAS
      syndrome (mitochondrial encephalopathy lactic acidosis stroke-like episodes) by
      using the method of immunohistochemical staining in the brain biopsy specimens
      with anti-mitochondrial antibody (AMA). METHODS: We performed immunohistochemical
      staining in 3 confirmed MELAS patients' paraffin-imbued brain biopsy specimens.
      RESULTS: Small vessel proliferation and the uneven thickness of the wall were
      found in the 3 MELAS patients. A lot of brown deposits was shown in the wall of
      small vessels and also noted in neurons. CONCLUSIONS: The main pathological
      change in the MELAS brain biopsy immunohistochemical staining with AMA was the
      small vessel proliferation, indicating that abnormal mitochondria accumulated in
      the vascular smooth muscle, endothelial cell and neurons of the lesion sites.
      This finding was consistent with the electron microscopic discovery and valuable
      for the diagnosis of MELAS.

PMID- 19576113
TI  - [The expression of DJ-1 protein in proteomic analysis of late-onset Alzheimer
      disease].
AB  - OBJECTIVE: To investigate the pathogenicity of late-onset Alzheimer disease from
      the viewpoint of comparative proteomic technology and to screen it from diseases
      with related protein markers. METHODS: Cerebral cortex tissue of temporal layer
      of 8 cases of late-onset Alzheimer disease and 5 cases of age-matched autopsied
      controls with normal brain was chosen for this study. Cerebral proteins were run
      through immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the
      first dimension and then vertical SDS-PAGE electrophoresis as the second
      dimension. Differential proteins were identified with visionworks LS and then
      analyzed with matrix assisted laser desorption ionization time of flight mass
      spectrometry (MALDI-TOF-MS) and electrospray ionization mass spectrometry (ESI
      MS). Finally, the protein was identified by searching in the data bank. RESULTS:
      Different 2-dimensional gel electrophoresis maps were obtained for the protein
      spots in the late-onset Alzheimer disease group and the control group gels.11
      protein spots showed a significantly differential expression between the two
      groups of cerebral cortex samples. It was found that the expression of DJ-1
      protein was increased in the late-onset Alzheimer disease group in comparison
      with the control group after searching in the database. CONCLUSION: DJ-1 protein
      may be a potential marker related to Alzheimer disease pathogenicity. This
      finding would be helpful to develop new drugs which focus on this protein and
      prevent neurodegeneration.

PMID- 19576115
TI  - [The correlation of CAGs repeat size with age of onset in patients with Kennedy's
      disease].
AB  - OBJECTIVE: To investigate the correlation of CAGs repeat size and age of onset in
      patients with Kennedy's Disease (KD). METHODS: We detected the number of CAG
      repeats in the androgen receptor genes in 30 patients with KD. The correlation of
      CAGs repeat size with age of onset was analyzed. At the same time, the Appel
      scale that could represent the degree of motor functional impairment was scored
      in every patient. The correlation of Appel scale with CAGs repeat size and the
      course of disease were analyzed. RESULTS: Significant correlation was found
      between the number of CAGs with age of onset (r = -0.671, P < 0.01). There was
      also correlation between the Appel score and the course of disease (r = 0.855, P
      < 0.01), but no correlation between the Appel score and the number of CAGs (r =
      0.100, P = 0.601). CONCLUSIONS: It is found that in Kennedy' disease, as well as
      in other CAG repeat diseases, the length of polyglutamine tract determines the
      age of onset, but has no correlation with the severity of the disease.

PMID- 19576114
TI  - [The statin dosage for achieving goal of cholesterol-lowering based on risk
      stratification in patients with ischemic cerebrovascular diseases].
AB  - OBJECTIVE: To explore statin dosages for targeting goal of LDL-C lowering on the
      basis of stroke risk stratification and the dosage-effective relation of statin
      and LDL-C lowering in Chinese patients with ischemic stroke and transient
      ischemic attack (TIA). METHODS: This is a prospective and open clinical trial
      patients with ischemic stroke/TIA within 6 months were enrolled and the dosages
      of atorvastatin were calculated based on risk stratification according to
      "Chinese Consensus for Prevention of Ischemic Stroke/TIA with Statin" (Chinese
      Consensus). A dose of 10 mg of atorvastatin daily to target LDL-C goal was taken
      as the standard dosage targeting goal (SDTG). Patients taking this dosage of
      atorvastatin constituted a SDTG group. Those who needed a daily dose of 20 mg or
      more of atorvastatin were randomized into an intensive dosage targeting goal
      (IDTG) group (atorvastatin 20 - 80 mg/d) and a standard dosage non-targeting goal
      (SDNTG) group (atorvastatin 10 mg/d without targeting goal). All patients took
      atorvastatin for 12 weeks. The primary outcome was the rate of targeting goal for
      LDL-C lowering at 2, 4 and 12 weeks, respectively and the secondary outcome was
      the occurence of recurrent stroke and other vascular events within 12 weeks. The
      main safety endpoint was serial adverse events including symptomatic intracranial
      hemorrhage. RESULTS: Altogether 102 cases were enrolled and 99 cases were
      followed up for 12 weeks. According to the Chinese Consensus, the rate of high
      risk, very high risk-I and very high risk-II was 44%, 28% and 28%, respectively.
      Targeting rate for LDL-C lowering was 77% - 85% at each time point in the SDTG
      and IDTG groups, being significantly higher than those in the SDNTG group (12% -
      16%, P < 0.01). No significant difference was found concerning the occurrence of
      recurrent stroke, other vascular events and safety endpoints among the three
      groups. The amplitude of LDL-C lowering was 32% - 35%, 46% - 49%, 51% - 52% and
      60% - 65% with corresponding to daily dosage of 10 mg, 20 mg, 40 mg and 80 mg
      atorvastatin. CONCLUSIONS: At least more than half of the patients after ischemic
      stroke/TIA need intensive statin therapy to target the LDL-C lowering goal. The
      dosage-effective relation of atorvastatin and LDL-C lowering in Chinese is
      similar to the reported data in other races.

PMID- 19576116
TI  - [An analysis of clinical factors for coronary artery calcification score].
AB  - OBJECTIVE: To evaluate the correlating clinical factors of coronary artery
      calcification score (CACS). METHODS: 141 patients suspected of coronary artery
      disease were included. They underwent multi-slice row computed tomography, pulse
      wave velocity (PWV), UCG and blood biochemistry within a period of 3 months. The
      subjects were divided into three groups according to CAC score: A (CACS = 0 -
      10), B (CACS = 11 - 400), C (CACS > 400). RESULTS: CACS was significantly
      associated with age, history of hypertension and diabetes mellitus. It was also
      associated with the presence of mitral annular calcification and aortic valve
      calcification, low ankle brachial pressure index (ABI) and high mean artery
      pressure (MAP) as well as high values of brachial ankle PWV (baPWV) and Upstroke
      time (UT). Multifactorial logistic regression analysis showed that the presence
      of aortic valve calcification and mitral annular calcification, the history of
      diabetes mellitus and high value of UT were independently correlated with severe
      coronary artery calcification. CONCLUSIONS: Aortic valve calcification, mitral
      annular calcification, history of diabetes mellitus, high value of UT were
      independently correlated with severe coronary artery calcification. Measurement
      of PWV and UCG should be performed before multi-slicerow computed tomography,
      because the assessment of coronary artery lumen narrowing with multi-slice row
      computed tomography can not be carried out accurately in the presence of severe
      coronary artery calcification.

PMID- 19576117
TI  - [A comparison of clinical and pathologic characteristics between Crohn's disease
      and intestinal tuberculosis].
AB  - OBJECTIVE: To search for the distinctive diagnostic features of Crohn's disease
      and intestinal tuberculosis in clinical manifestations with methods widely used
      clinically. METHODS: A retrospective study enrolled 33 Crohn's disease and 34
      intestinal tuberculosis inpatients in West China Hospital of Sichuan University
      from 1996 to 2007. The clinical characteristics and key points of differential
      diagnosis were analyzed. All the pathological sections were studied again.
      RESULTS: The total duration of symptoms in patients with a diagnosis of Crohn's
      disease was longer than that in patients with intestinal tuberculosis (P < 0.05).
      The incidence of colectomy is significantly higher in Crohn's disease than in
      intestinal tuberculosis because of intestinal obstruction or undefined diagnosis
      (P < 0.05). Hematochezia, extra-intestinal manifestation and ileus occurred
      significantly more in Crohn's disease than in intestinal tuberculosis (P < 0.05).
      Night sweating and hypoalbuminemia occurred significantly more in intestinal
      tuberculosis than in Crohn's disease (P < 0.05). The positive rate of serum
      antibodies to mycobacterium and increased erythrocyte sedimentation rate is
      higher in intestinal tuberculosis than in Crohn's disease (P < 0.05). Cobblestone
      sign and fissure-shape ulcers were only found in Crohn's disease, while circular
      ulcer occurred significantly more in intestinal tuberculosis (P < 0.05). The
      involvement of stomach, jejunum or ileum was significantly more in Crohn's
      disease than in intestinal tuberculosis (P < 0.05).Granulomas were more common in
      intestinal tuberculosis than in Crohn's disease (P < 0.05) and the site of
      granulomas was valuable for differential diagnosis. In all the Crohn's disease
      specimens, lymphoid aggregates in the lamina propria or submucosa were
      significantly more in surgically resected specimens than in endoscopic biopsies
      (P < 0.05). CONCLUSIONS: There are definitely some different features between the
      two diseases. It is essential to review the whole clinical data of the patient.
      The frequency of granulomas and the distribution of chronic inflammation are
      identified as histological parameters that can be used to differentiate
      tuberculosis and Crohn's disease.

PMID- 19576118
TI  - [The mechanisms of thalidomide in treatment of angiodysplasia due to hypoxia].
AB  - OBJECTIVE: To investigate the inhibitory effect of thalidomide on angiodysplasia.
      METHODS: Excisional intestinal specimens were collected and immunohistochemical
      examination was carried out. The human umbilical vein endothelial cells were
      cultured in vitro to exponential phase of growth, divided into six groups and
      synchronized for 24 hours. They were then stimulated with thalidomide (40 - 100
      microg/ml) for 72 hours. MTT assay was used to assess cellular proliferation.
      ELISA, real-time quantitative PCR and western blot were applied to detect the
      expression of VEGF/HIF-1alpha of human umbilical vein endothelial cells (HUVEC).
      RESULTS: Immunohistochemical analysis of intestinal pathological specimens
      demonstrated higher expression of VEGF. ELISA showed that the expression of VEGF
      under hypoxia was obviously higher than that under normoxia [(1199.3 +/- 61.4)
      ng/L vs (864.7 +/- 41.2) ng/L, P < 0.05]. Real-time quantitative PCR and Western
      blot discovered that thalidomide inhibited the expression of VEGF/HIF-1alpha of
      HUVEC (P < 0.05). The effect of thalidomide was dose-dependent. CONCLUSIONS:
      Thalidomide can suppress the expression of HIF-1alpha and VEGF in HUVEC in vitro
      and then inhibit angiodysplasia, which may play a significant role in stopping
      the rebleeding in patients with recurrent gastrointestinal bleeding.

PMID- 19576119
TI  - [The clinical significance of noninvasive inflammatory markers in exhaled breath
      condensate and induced sputum in persistent asthmatic patients].
AB  - OBJECTIVE: To assess the clinical significance of three different noninvasive
      airway inflammatory indices in induced sputum and exhaled breath condensate (EBC)
      from persistent asthmatic patients. METHODS: Moderate and severe asthmatic
      patients were prescribed inhaled corticosteroids combined with long-acting
      beta(2) agonists for a month. The symptom scores and percentage of predicted
      value of forced expiratory volume in one second (FEV(1)) (FEV(1)%pred) were
      measured while the concentrations of H(2)O(2), NO(3)(-)/NO(2)(-), and cysteinyl
      leukotriene E(4) (LTE(4)) in induced sputum and EBC were detected before and
      after therapy. RESULTS: A total of twenty-five subjects with moderate and severe
      asthma were enrolled. By combined therapy for one month the asthma symptoms
      relieved and FEV(1)%pred improved significantly (P < 0.01). The concentrations of
      H(2)O(2), NO(3)(-)/NO(2)(-) and LTE(4) in induced sputum and EBC declined
      significantly (P < 0.01) although the concentrations were still higher than those
      at normal baseline. More marked reduction of H(2)O(2) and NO(3)(-)/NO(2)(-)
      compared to LTE(4) was observed. It was revealed that the concentrations of
      H(2)O(2)and NO(3)(-)/NO(2)(-) but not of LTE(4) in EBC were negatively correlated
      with FEV(1)%pred (P < 0.01) and positively with symptom scores. Such correlations
      were also found in H(2)O(2) in induced sputum with FEV(1)%pred and symptom scores
      as well as NO(3)(-)/NO(2)(-) in induced sputum with FEV(1)%pred. The improvement
      of FEV(1)%pred after treatment was positively correlated with the reduction of
      H(2)O(2) and NO(3)(-)/NO(2)(-) both in induced sputum and EBC. Correlation
      analysis also demonstrated three inflammatory indices were equivalent in induced
      sputum and EBC (correlation coefficient of H(2)O(2), NO(3)(-)/NO(2)(-) and
      LTE(4), 0.759, 0.826 and 0.653, respectively. P < 0.01). CONCLUSIONS: (1)
      Combined therapy with inhaled corticosteroid plus long-acting beta(2) agonist
      significantly improves the clinical symptoms and lung function of patients with
      moderate and severe asthma companies with marked suppression of airway
      inflammation. (2) Both of EBC and induced sputum sampling are valuable
      noninvasive procedures for detecting asthma airway inflammation, however, EBC
      technique is superior in safety and reproducibility. (3) H(2)O(2) and NO(3)(
      )/NO(2)(-) seem to be more sensitive indices in diagnosis and monitoring asthma
      compared to LTE(4).

PMID- 19576120
TI  - [A comparison of efficacy and tolerance of nateglinide and acarbose monotherapy
      in type 2 diabetes mellitus].
AB  - OBJECTIVE: To compare the efficacy and tolerability of nateglinide with those of
      acarbose in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: This multi
      center, randomized, double-blind, parallel-arm study compared the efficacy and
      tolerability of nateglinide (120 mg, 3/d, n = 119) and those of acarbose (100 mg,
      3/d, n = 118) during a 12-week treatment in T2DM patients uncontrolled by diet
      with glycosylated haemoglobin (HbA1c) 6.5% - 11.0%. RESULTS: Monotherapy with
      nateglinide (120 mg, 3/d) or acarbose (100 mg, 3/d) decreased HbA1c to a similar
      extent during 12-week treatment. The mean change from baseline to end-point in
      HbA1c was (-0.90 +/- 0.98)% and (-0.83 +/- 0.81)% in patients receiving
      nateglinide and acarbose, respectively, with no significant difference between
      the two groups (P > 0.05). The decrease in fasting plasma glucose (FPG) was
      similar between nateglinide and acarbose (P > 0.05). The mean change in 2-hour
      postprandial plasma glucose (PG2h) was (-1.45 +/- 2.74) mmol/L and (-2.20 +/-
      2.21) mmol/L in patients receiving nateglinide and acarbose (P = 0.0017). Body
      weight was significantly decreased in both groups at the end-point (P < 0.05),
      although the decrease was more with acarbose than nateglinide [(-0.66 +/- 1.79)
      kg vs (-2.06 +/- 2.00) kg, P = 0.0000]. And the proportion of patients
      experiencing any presumed drug related adverse events was not significantly
      different between the two groups. CONCLUSIONS: Nateglinide (120 mg, 3/d) is
      effective and well tolerated in T2DM patients uncontrolled by diet, demonstrating
      similar HbA1c reductions as compared with acarbose (100 mg, 3/d).

PMID- 19576121
TI  - [The changes of thyrotropin level in euthyroid population: a 5-year follow-up
      study in communities with different iodine intakes].
AB  - OBJECTIVE: To determine the factors that influence the development of abnormal
      thyrotropin (TSH) level in an euthyroid population. METHODS: We conducted a
      follow-up study in 3 communities with different iodine status. Of the 3403
      euthyroid subjects at baseline screened in 1999, 80.1% (n = 2727) was visited and
      sampled in 2004 for measuring TSH, thyroid peroxidase antibody (TPOAb) and
      thyroglobulin antibody (TgAb). RESULTS: Iodine status in the 3 communities were
      stable. Decreased TSH level (< 0.3 mU/L) developed in 2.5% (n = 68) of sampled
      subjects, while raised TSH level (> 4.8 mU/L) in 2.4% (n = 64). A logistic
      analysis showed that risk factors for developing decreased TSH level included
      positive conversion of TPOAb (OR = 5.5), positive TPOAb both in 1999 and in 2004
      (OR = 4.0), positive TgAb in 2004 (OR = 3.7) and TSH < 1.0 mU/L in 1999 (OR =
      2.6). Risk factors involved in developing raised TSH level included iodine status
      of Zhangwu community (OR = 4.1), iodine status of Huanghua community (OR = 3.9),
      positive TgAb in 2004 (OR = 3.7), positive TPOAb both in 1999 and 2004 (OR =
      3.6), positive conversion of TPOAb (OR = 2.7) and TSH > 1.9 mU/L in 1999 (OR =
      2.6). CONCLUSIONS: Exposure to long-term iodine excess imposes danger of
      developing hypothyroidism. The risk will be even higher when exposing to iodine
      adequacy after correction of iodine deficiency. An interval between 1.0 and 1.9
      mU/L of TSH level was optimal with the least probability of developing abnormal
      TSH level.

PMID- 19576122
TI  - [The early diagnosis and clinical analysis of 57 cases of acquired hemophagocytic
      lymphohistiocytosis].
AB  - OBJECTIVE: To explore the significance of NK cell activity, interleukin-2
      receptors (sCD(25)) and glycosylated ferritin in the early diagnostic of acquired
      hemophagocytic lymphohistiocytosis (HLH). METHODS: 57 patients suspected of HLH
      from June 2005 to May 2008 and 25 healthy subjects were enrolled in the study.
      The patients suspected of HLH were divided into three groups i.e. (1) a group
      with diagnosis confirmed at first visit; (2) a group with diagnosis confirmed at
      subsequent visit and (3) a group with diagnosis unconfirmed according to HLH-2004
      diagnostic criteria. Healthy subjects were enrolled as control. NK cell activity
      was determined with a released LDH assay. The percentage of glycosylated ferritin
      was determined with phytohemagglutinin adsorption assay. sCD(25) was examined
      with ELISA double antibody sandwich assay. We compared the coincidence of each
      diagnostic index before and after diagnosis. RESULTS: The median percentage of NK
      cell activity was significantly lower in the first group (18.3 +/- 5.6)% and the
      second (16.7 +/- 6.7)% than that in the third group (33.4 +/- 6.8)% or in the
      controls (36.6 +/- 5.0)%. The median percentage of glycosylated ferritin was also
      significantly lower in the first group (15.4 +/- 2.0)% and the second group (16.9
      +/- 3.4)% than that in the third group (40.4 +/- 3.0)% or in the controls (45.2
      +/- 2.2)%. Meanwhile, the median level of sCD(25) was significantly higher in the
      first group (12 916 +/- 4328) ng/L and the second group (12 117 +/- 5465) ng/L
      than that in the third group (4728 +/- 1482) ng/L or in the controls (3841 +/-
      993) ng/L. Furthermore, NK cell activity, sCD(25) and glycosylated ferritin were
      abnormal in all the patients in the early stage of HLH. CONCLUSION: NK cell
      activity, sCD(25) and glycosylated ferritin may be helpful markers for the early
      diagnosis of HLH.

PMID- 19576124
TI  - [A new prognostic stratification for patients with acute myeloid leukemia].
AB  - OBJECTIVE: To evaluate the impact of the percentage of residual blasts in bone
      marrow at the end of induction chemotherapy (T1) or during myelosuppression phase
      (T2) on prognosis of de novo acute myeloid leukemia (AML) (non M(3)) in 105
      cases. To refine AML risk-stratification by combining the percentage of residual
      blast cells (T1 or/and T2) with cytogenetic data based the South West Oncology
      Group (SWOG) criteria. METHODS: The data of 105 de novo AML (non M(3)) patients
      hospitalized between January 1st 1999 and February 1st 2008 were retrospectively
      reviewed. Results were analyzed with SPSS15.0 software. RESULTS: (1) Patients
      were divided into two subgroups by a cutoff of 5% residual bone marrow blasts at
      T1 or T2 time point. Patients with percentage of residual bone marrow blast cells
      < 5% had better complete remission (CR) rate, relapse-free survival (RFS) and
      overall survival (OS) than the patients with percentage > or = 5% at T1 or T2.
      The percentage of residual bone marrow blast cells at T1 was correlated with that
      at T2. (2) The prognosis of patients with intermediate karyotypes with percentage
      < 5% at T1 or T2 was similar to that of the patients with favorable karyotypes.
      The patients with intermediate karyotypes and percentage of residual bone marrow
      blasts > or = 5% at T1 or T2 are defined as a subgroup with prognosis similar to
      that of patients with unfavorable karyotypes. (3) COX regression analysis showed
      that the percentage of residual bone marrow blasts at T1 or T2 is an independent
      prognostic factor of AML. The percentage of residual bone marrow blasts at T1 may
      be more helpful in prognostication than that at T2. CONCLUSION: AML patients with
      percentage of residual bone marrow blasts < 5% after induction chemotherapy (T1
      or T2) have better CR rate, RFS, OS than the patients with percentage > or = 5%
      at the same time point. Combination of cytogenetics and percentage of residual
      bone marrow blasts at T1 or T2 is helpful to divide patients with intermediate
      karyotypes into two subgroups with different prognosis. Thus, a better decision
      of treatment strategy can be designed.

PMID- 19576143
TI  - Ageing population: status, challenges and opportunities for health care providers
      in Pakistan.

PMID- 19576144
TI  - Attenuation of somatodendritic responses to 8-hydroxy-2-di-npropylamino tetralin
      following long-term dietary sugar consumption in rats.
AB  - OBJECTIVE: To determine changes in response to a selective serotonin-1A receptor
      agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) following long-term
      consumption of sugar as part of meal in rats. STUDY DESIGN: Experimental study.
      PLACE AND DURATION OF STUDY: The Department of Biochemistry, University of
      Karachi, from June to August 2005. METHODOLOGY: The study was conducted on 24
      male albino Wistar rats. Sugar containing diet was prepared by mixing standard
      rodent diet and table sugar in the ratio of 3:1 (w/w) and rats were fed freely on
      this diet. Control rats were fed freely on standard rodent diet. After five weeks
      of treatment, control and sugar diet treated animals were injected with 8-OH
      DPAT, at a dose of 0.5 mg/ml/kg, to monitor the effects of drug on food intake
      and brain serotonin (5-hydroxytryptamine, 5-HT) metabolism. Dissected neural
      tissue was analyzed electrochemically and findings were compared by Newman-Keuls
      test. RESULTS: Administration of 8-OH-DPAT elicited hyperphagia and decreased 5
      HT metabolism in normal diet treated rats. The neurochemical and hyperphagic
      responses to 8-OH-DPAT were smaller in sugar than normal diet treated animals
      suggesting a downregulation of somatodendritic responses in sugar diet treated
      animals. CONCLUSION: A decrease in serotonin metabolism but not an increase in
      the responsiveness of somatodendritic 5-HT-1A receptors is involved in sugar-rich
      diet induced hyperphagia.

PMID- 19576145
TI  - Use of exercise tolerance test and thallium stress test in the diagnosis of
      ischemic heart disease in soldiers.
AB  - OBJECTIVE: To determine the role of Exercise Tolerance Test (ETT) and Thallium
      Stress Test (TST) in the detection of Coronary Artery Disease (CAD) among
      soldiers. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: This
      study was conducted at Combined Military Hospital (CMH), Multan, Pakistan, from
      2002 to 2004. METHODOLOGY: There were 291 male soldiers between ages 30 and 45
      years who presented with chest pain and had normal resting ECG. All patients were
      subjected to ETT. Positive ETT cases had Coronary Angiogram (CA) as the gold
      standard. Negative cases were subjected to TST. Normal CA cases also had TST to
      rule out microvascular disease. Those with normal ETT and positive CAD risk
      factors also had TST. Those with negative TST had CA as service requirement.
      RESULTS: All 291 cases had ETT, 130 cases were found positive, 161 had negative
      ETT. When CA was done on 130 positive cases, 95 had CAD (true positive, TP) and
      35 had normal coronaries (false positive, FP). Out of the 161 negative ETT cases,
      128 had normal coronaries (true negative, TN) and 33 had CAD (false negative,
      FN). TST was conducted on 196 cases, out of which 78 cases were found positive
      and 118 had negative TST. When subjected to CA, out of 78 positive cases, 30 had
      CAD (TP) and 48 had normal coronaries (FP). Out of 118 negative TST cases, 115
      had normal coronaries (TN) and 3 had CAD (FN). ETT was found to have sensitivity
      of 74.2%, specificity of 78.5%, Positive Predictive Value (PPV) of 73.1%,
      Negative Predictive Value (NPV) of 79.5% and test accuracy of 76.6%. TST had
      sensitivity of 90.9%, specificity of 70.6%, PPV of 38.5%, NPV of 97.5% and
      accuracy of 74.0%. CONCLUSION: TST was found to be more sensitive and less
      specific than ETT in the diagnosis of CAD.

PMID- 19576146
TI  - A study of flare-ups following single-visit root canal treatment in endodontic
      patients.
AB  - OBJECTIVE: To determine the frequency of flare-ups in single-visit endodontic
      treatment and the associated factors. STUDY DESIGN: Observational. PLACE AND
      DURATION OF STUDY: Baqai Dental College Hospital, Karachi, from November 2005 to
      May 2006. METHODOLOGY: One hundred patients were assigned for single-visit root
      canal treatment. Patients that defaulted after the first appointment (incomplete
      treatment) were excluded from the study. For each tooth treated, the clinical
      factors and conditions existing before and after the completion of treatment were
      recorded. This data included patient's age, gender, type of tooth, pre-operative
      status of pulp and periapical tissues and recording pain and swelling (flare-ups)
      postoperatively after 1 day, 7 days and 1 month. The significance of results was
      obtained by applying paired-sample t-test and Pearson X2 test. RESULTS: Three of
      one hundred cases showed flare-ups after treated in single appointment. On the
      other hand, a marked number (n=97) of cases did not show flare-ups during the
      study period. None of the studied variables showed any statistically significant
      bearing on rate of flare-ups in single appointment root canal treatment.
      CONCLUSION: The single-visit root canal treatment was safe in terms of endodontic
      flare-ups as far as results of this study are concerned. It was safer in both
      vital and non-vital teeth, and even in teeth with periapical pathosis.

PMID- 19576147
TI  - Transhiatal esophageal surgery for malignancy--a 7-year experience at a tertiary
      care hospital.
AB  - OBJECTIVE: The aim of this study was to determine the outcomes of transhiatal
      esophagectomy for dysphagia for esophageal malignancy in terms of short and long
      term morbidity and mortality and to determine the survival series. STUDY DESIGN:
      Case series study. PLACE AND DURATION OF STUDY: South and West Surgical Ward,
      Mayo Hospital, Lahore, from January 2001 to December 2007. METHODOLOGY: All
      patients referred electively or admitted through OPD presenting with features of
      progressive dysphagia due to malignancy were included in the study. The patients
      were investigated for site of stricture and extent of growth into the surrounding
      structures. All underwent transhiatal esophagectomy and gastric tube or colon was
      used as the conduit to restore continuity. Patients with squamous cell variety
      were referred to oncology department for chemoradiotherapy postoperatively.
      Morbidity and in-hospital mortality were recorded. RESULTS: A total of 42
      patients were operated electively for malignant stricture esophagus through
      transhiatal approach. Site of lesion were 5 (11.9%) upper, 13 (31%) middle and 24
      (58%) at lower end of esophagus. The TNM staging were stage I, IIa, IIb, III and
      IV in zero (0), 5 (11%), 10 (22%), 24 (57.8%) and 3 (7.1%) respectively. Mean
      operating time was 154 minutes and average blood loss of 371 ml. Postoperative
      complications included pneumothorax 16.7%, pulmonary complication (16.7%),
      anastomotic leakage (9.5%), wound infection (3.4%), recurrent laryngeal nerve
      injury (4.8%) and stricture formation (4.8%). Only 3 (7.1%) 30-day in-hospital
      mortality was recorded. CONCLUSION: Transhiatal esophagectomy is the surgical
      treatment of choice for resection of carcinoma esophagus specifically at the
      lower and mid-esophageal levels. The frequency of complications is lower as
      compared to transthoracic approach and the early stage of presentation can lead
      to high 5-year survival ratios.

PMID- 19576148
TI  - Correlation of steatosis with fibrosis and necro-inflammation in chronic
      hepatitis C infection in the absence of confounding factors.
AB  - OBJECTIVE: To assess the frequency and degree of hepatic steatosis in patients of
      chronic hepatitis C infection and determine its correlation with stages of
      fibrosis and necro-inflammatory grades. STUDY DESIGN: Cross-sectional study.
      PLACE AND DURATION OF STUDY: The study was carried out in the Department of
      Pathology (Histopathology), Army Medical College, Rawalpindi, from March 2006 to
      March 2007. METHODOLOGY: Patients who had undergone a liver biopsy for evaluation
      of hepatitis C virus infection were included in the study. Demographic
      characteristics and laboratory data were collected at the time of biopsy. First
      hundred biopsy specimens meeting the inclusion criteria were assessed for
      steatosis, necro-inflammation and fibrosis. RESULTS: Steatosis was present in 46
      patients and graded as mild (41.3%), moderate (54.3%) and severe (4.3%). An
      overall significant correlation was found between grades of steatosis with stage
      of fibrosis (p < 0.0001) but no correlation was found with necro-inflammatory
      grades. Only focal necrosis revealed weak correlation with grades of steatosis (p
      < 0.003). CONCLUSION: These results suggest a possible role of the hepatitis C
      virus itself in the pathogenesis of steatosis and indicate its close relationship
      with fibrosis and focal degeneration in chronic hepatitis C. Necro-inflammation
      seen in liver biopsy is host immune reaction to hepatitis C virus and is not
      related to steatosis.

PMID- 19576149
TI  - Anthropometric and metabolic indicators in hypertensive patients.
AB  - OBJECTIVE: To determine the relationship between anthropometric variables with
      blood glucose and lipid concentrations in different stages of hypertension and
      evaluate the risk factors involved in progression of pre-hypertension stage in to
      clinical hypertension stage-1. STUDY DESIGN: Case-control study. PLACE AND
      DURATION OF STUDY: National Institute of Cardiovascular Disease and General
      Practitioner's Clinics, Karachi, from 2005 to 2007. METHODOLOGY: The study was
      conducted on 276 participants aged 25-65 years and classified into four
      categories of control, prehypertension (pre-HTN), hypertension (HTN) stage I and
      II, according to 7th JNC report. Anthropometric measurements and blood chemistry
      were obtained. The relationship between obesity indices (Body Mass Index [BMI],
      Waist Circumference [WC], Waist Hip Ratio [WHpR], Waist Height Ratio [WHtR],
      Basal Metabolic Rate [BMR] and Cardiovascular Disease [CVD] risk factors [blood
      pressure, serum lipids and glucose levels]) were investigated. The analysis of
      variance and test of Pearson's coefficient correlation were applied to assess
      relationship of all the variables. RESULTS: The mean WHR had significant
      correlation with both systolic and diastolic BP in all groups of HTN, as well as
      with blood glucose level in control and pre-HTN groups. BMI was positively
      correlated with cholesterol (r=0.29) and triglyceride (r=0.25) in HTN stage-1.
      Impaired and high blood glucose levels were found in pre-HTN group; all lipid
      parameters except triglycerides were higher in HTN stage I. CONCLUSION: WHR was
      positively and independently related to occurrence of arterial hypertension.
      Elevated levels of WHR, BMI, fasting blood glucose, total cholesterol and
      triglycerides were responsible for progression of pre-HTN stage in to HTN stage
      1.

PMID- 19576151
TI  - Perinatal outcome in high risk pregnancies.
AB  - OBJECTIVE: To determine the perinatal outcome of high risk pregnancies, in terms
      of perinatal mortality, Apgar score, birth weight and neonatal complications in
      first week after birth. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY:
      Obstetric Department of Sir Syed Trust Hospital, Karachi, from January to
      December 2007. METHODOLOGY: All antenatal patients attending the Outpatient
      Department were interviewed, after informed consent. Those who fulfilled the
      required criteria were grouped in 2 categories; high risk (group A cases) and low
      risk (group B control) pregnancies according to the risk factors identified in
      the history. All singleton pregnancies from 28th weeks of gestation till delivery
      were included in the study. All pregnant women, who had multiple pregnancies or
      congenital malformations were excluded. Patients were followed till delivery and
      neonatal outcome was assessed in both the groups. Outcome measures were recorded.
      RESULTS: There were a total of 282 patients studied. The number of patients in
      group A were 162 and in group B, 120. Anaemia 98 (60.49%), pregnancy induced
      hypertension 24 (14.8%) and preterm labour 26 (16%) were identified as the major
      risk factors in group A. There were 12 (7.40%) stillbirths and 5 (3.08%) early
      neonatal deaths in group A, while there was 1 (0.84%) stillbirth and no neonatal
      death in group B (p=0.004, RR=1.72). There were 58 (35.80%) neonates with low
      birth weight in group A, while the same were only 4 (3.33%) in group B, which was
      statistically significant (p=0.001, RR=1.98). Poor Apgar score of < or = 7 at 1
      minute was observed in 6 (4%) and at 5 min was observed in 5 (3.33%), while none
      of the neonates in group B was born with Apgar score of less < or = 7 at 1 or 5
      minute (p=0.036, RR=1.83; p=0.068, tR=1.82 respectively). Meconium aspiration
      syndrome was observed in 7 (4.3%) cases in group A, and 2 (1.66%) in group B,
      which was statistically insignificant. Complication rate among the neonates was
      statistically not significant between the two groups. CONCLUSION: Perinatal
      mortality was twice as high in high risk group compared to low risk group.
      However, the complications in the neonates were statistically insignificant
      between the two groups.

PMID- 19576150
TI  - Comparison of oral versus injectable vitamin-D for the treatment of nutritional
      vitamin-D deficiency rickets.
AB  - OBJECTIVE: To assess the safety and acceptability of a single dose of vitamin-D
      versus the efficacy of injectable Vitamin-D versus oral vitamin-D. STUDY DESIGN:
      Case control. PLACE AND DURATION OF STUDY: It was carried out at the Department
      of Paediatrics, Kharadar General Hospital, Karachi, from August 2003 to April
      2004. METHODOLOGY: Children of the age of 6 months to 3 years with clinical,
      biochemical and radiological evidence of vitamin- D deficiency rickets were
      included. The history, clinical examination, complete blood picture, serum
      calcium. Phosphorus, alkaline phosphatase and X-ray of wrist joint were done. The
      children were divided into two groups A and B. Group A was given oral vitamin-D
      and group B was given intramuscular injection of vitamin-D on the first day and
      then they were followed for two more visits at 30 and 90 days with clinical,
      biochemical and radiological examinations to assess the outcome. RESULTS: There
      were 50 confirmed cases of rickets in each group. The mean age was 10.9+5.1
      months and 14.7+8.1 months in group A and B respectively. In these children,
      clinical features were weakness, difficulty in walking, frontal bossing, ribcage
      deformity and widening of wrist were seen. After one dose of vitamin-D
      (cholecalciferol), there was appreciable gain of weight and height and raised
      levels of alkaline phosphatase became normal during follow-up. Radiological
      florid rickets and non-florid rickets in both groups healed clinically during
      follow-up period. Oral and injectable forms of vitamin-D (cholecalciferol) were
      effective but injectable form was shown to be statistically significant. There
      were no undesirable side effects and both forms of treatment were well-tolerated.

PMID- 19576152
TI  - Visual outcome and complications after removal of posterior segment intraocular
      foreign bodies through pars plana approach.
AB  - OBJECTIVE: To assess the visual outcome and complications after removal of
      posterior segment retained intraocular foreign bodies through pars plana
      approach. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of
      Ophthalmology, Jinnah Postgraduate Medical Centre, Karachi, from May 2005 to May
      2006. METHODOLOGY: Fifty patients with history of ocular foreign body were
      admitted through outpatient department and emergency. History, visual acuity,
      ocular and general examination was done. The foreign body was localized with the
      radiograph of the skull and ultrasonography. Primary repair was done in patients
      with open wounds. Pars plana vitrectomy, magnetic or forceps extraction of
      foreign body was done as required visual outcomes and complications were noted.
      RESULTS: Among the 50 patients, there were 45 (90%) males and 5 (10%) females.
      Average age of the patients was 31.52 +9.52 (ranging from 20 to 50) years. The
      pre-operatively visual acuity finger counting to perception of light was 78%
      cases. The best corrected final visual acuity was 6/6 in 1 (2%) patient, 6/9 in 5
      (10%) patients, 6/12 in 5 (10%) patients, 6/18 in 3 (6%) patients, 6/24 and 6/36
      in 4 (8%) patients each, 6/60 in 4 (8%) patients, finger counting in 8 (16%)
      patients, hand movement in 4 (8%) patients, projection of light in 9 (18%)
      patients and no projection of light in 3 (6%) patients. The postoperative
      complications were corneal opacity in 8 (16%) patients, anterior chamber
      inflammatory reaction in 6 (12%) patients, increased intraocular pressure in 1
      (2%) patient, silicone oil in anterior chamber in 1 (2%) patient, macular scar in
      7 (14%) patients, cystoid macular edema in 1 (2%) patient, endophthalmitis in 4
      (8%) patients, retinal detachment in 11 (22%) patients and phthisis bulbi in 3
      (6%) patients. CONCLUSION: Acceptable visual results were achieved after the
      removal of posterior segment intraocular foreign bodies by vitrectomy. However,
      multiple complications can be encountered which require meticulate postoperative
      care.

PMID- 19576153
TI  - Intestinal amoebiasis in children and its effect on nutritional status.
AB  - OBJECTIVE: To determine the frequency and clinical presentation of amoebic
      diarrhea in children and its effect on the nutritional status of the affected
      children. STUDY DESIGN: Descriptive. PLACE AND DURATION OF STUDY: Department of
      Diarrhea Treatment Unit (DTU), Dow Medical College and Civil Hospital, Karachi,
      from November 1998 to April 2001. METHODOLOGY: Paediatric patients between the
      ages of > 1 month to 15 years were included, who visited the DTU of the
      department with diarrhea. Stool samples of all these patients were checked under
      microscope for the vegetative forms of Entamoeba Histolytica (E.H.). Patients who
      were positive for E.H. were evaluated for the symtomatology including the type of
      diarrhea {acute watery diarrhea (AWD) or dysentery}, abdominal pain, tenesmus and
      nausea/vomiting. Examination carried out was assessed for state of hydration,
      fever and anaemia and nutritional status of those less than 5 years of age. The
      patients were divided into three age groups to assess the association of the age
      with severity and type of clinical presentation. Chi- square test was applied to
      calculate the p-values. P-values of 0.05 or less were considered statistically
      significant. RESULTS: The stool samples of 3870 patients with diarrhea were
      examined under microscope. Three hundred and twenty eight (8.47%) of these
      samples were positive for E.H. The difference between the number of patients
      presenting with acute watery diarrhea n=157, 47.86% and with dysentery n=171,
      52.13% was found to be statistically non-significant (p=0.364). Two hundred and
      seventy seven (84.45%) patients had tenesmus, while abdominal pain was present in
      287 (87.5%). Fever and malnutrition were present in 169 (51.52%) patients each.
      Malnutrition was significantly most frequent in 1-5 years of age groups (n=98,
      57.98%, p=0.026). The nutritional evaluation of the 272 under-5 children with
      amoebic diarrhea showed a significantly normal status in 123 (45.55%, p-value <
      0.001). All the signs and symptoms followed a similar trend with 1-5 years age
      group being the most affected group. However, the frequency of blood in stools
      increased in direct proportion to the increasing age. CONCLUSION: Although
      dysentery was the more common presenting complaint, almost half of the patients
      presented with watery diarrhea. Most of the patients with dysentery were under
      the age of 5 years. Fever was present in a high number of patients. The age group
      most affected by amoebiasis and malnutrition was 1-5 years.

PMID- 19576154
TI  - Bilateral tension pneumothoraces following coronary artery bypass grafting.
AB  - It is an unusual case of bilateral tension pneumothoraces developing in the
      postoperative period in a patient who underwent total arterial revascularization
      for two vessel coronary artery disease. The patient had been a previous heavy
      smoker and at operation had been noted to have thin walled lung parenchyma with
      multiple small bullae mainly in the left upper lobe. He suddenly developed
      bilateral pneumothoraces following intermittent continuous positive airway
      pressure requiring initially bilateral needle decompression followed by chest
      drain insertion. He recovered well and the air leak sealed after 3 days.

PMID- 19576155
TI  - Gastropleural fistula: an unusual sequel of blunt chest trauma.
AB  - In the October 2005 Earthquake in mountainous Azad Kashmir and adjacent areas in
      Pakistan, a young female sustained crush injury chest and upper abdomen. She
      remained hospitalized with lower chest pain. All initial investigations were
      normal and she was discharged symptom-free on conservative management. Six months
      later, she developed acute left sided chest pain and dyspnoea. Provisional
      diagnosis of empyema was made on X-ray, and tube thoracostomy was done.
      Diagnostic VATS revealed gastropleural fistula secondary to necrosis of herniated
      stomach. Resection of necrosed stomach, repair of diaphragm and decortication and
      transthoracic repair with lower thoracoplasty two months later was performed but
      both were unsuccessful. After another 02 months, a Roux-en-Y gastrojejunostomy at
      fistula site was fashioned which proved curative.

PMID- 19576156
TI  - Primary adrenal lipoma.
AB  - A case report of primary adrenal lipoma is being presented. A 35-year-old male,
      initially presented with pain in right loin and was admitted to Urology Unit of
      Prince Abdullah Bin Abdul Aziz Hospital, Bisha, KSA, for frank hematuria. The
      tumour was suspected on IVU and ultrasound abdomen and confirmed on CT-scan of
      abdomen. Right adrenalectomy was successfully performed and histopathology
      confirmed the diagnosis of adrenal lipoma.

PMID- 19576157
TI  - Distal ileal perforation secondary to ingested foreign bodies.
AB  - A 22-year-old man was admitted with abdominal pain, nausea and vomiting secondary
      to ingestion of multiple foreign bodies. He was found to be in increasing
      distress with an increase in abdominal pain and distention and no passage of
      foreign bodies. Patient underwent a laparotomy. Foreign bodies removed from
      perforated distal ileum included 8 big size (10 cm) plastic clothes pegs, a 10 cm
      pencil, couple of stones, a 10 cm wood nail, nail scissors and a small size
      battery. In case of foreign body ingestion, especially in mentally-ill patients,
      the patient should be carefully examined because of the potential risk of
      obstruction and bowel perforation, more so, if the foreign body is a battery
      which can puncture causing corrosive injury as well.

PMID- 19576158
TI  - Primary intraosseous squamous cell carcinoma of the mandible arising de novo.
AB  - Primary intraosseous squamous cell carcinoma is an odontogenic tumour with
      aggressive behaviour usually noticed in 6th to 7th decades of life. The tumour is
      characterized by progressive swelling of the jaw, pain and loosening of teeth.
      Microscopically, the lesion is showing foci of keratinising cells separated by
      collagenous connective tissue stroma. A case of primary intraosseous squamous
      cell carcinoma of mandible arising de novo in a 40-year-old man is reported.

PMID- 19576159
TI  - Ureteric schistosomiasis with obstructive uropathy.
AB  - A 25-year-old male Nigerian undergraduate who had earlier been treated with
      praziquantel for schistosomal epidydymitis presented with clinical features of
      pyelonephritis, and radiological appearances of bilateral hydroureteronephrosis
      with fibrosis of lower ureters. Surgical resection of the ureters, Boari flap and
      Psoas hitch reconstruction were done. The histology of the resected ureters
      proved schistosomiasis. He was subsequently treated with praziquantel and
      artemether. This case highlights the insidious nature of schistosomiasis
      infection, possibility of progression of primary infection with complications or
      probable reinfection in a previously treated individual. In any case, surgical
      intervention may be necessary in those who present late with severe ureteric
      stricture and also to prevent progressive renal damage.

PMID- 19576160
TI  - Small intestinal tumours.
AB  - Small bowel neoplasms continue to be an enigma to the clinicians. The insidious
      onset, the subtlety of the signs, the lack of definitive pre-operative diagnostic
      tests with often variable efficacies makes them difficult to diagnose. Small
      bowel consciousness is crucial in diagnosing and treating these tumours. This
      review aims to increase awareness of small bowel tumours in terms of
      epidemiology, diagnosis and treatment.

PMID- 19576161
TI  - Variations in powder/liquid ratio of a restorative and luting glass ionomer
      cement in dental clinics.
AB  - A survey was conducted to ascertain the variations practiced in powder/liquid
      (P/L) ratio of Glass Ionomer Cement (GIC) used as restorative and luting material
      in dental clinics of Karachi. It has been observed that in the use of GIC brands,
      33% (Fuji 2) and 36% (Gold Label 2) of the dentists, did not follow the
      recommended P/L ratios for restorative purposes. Similarly, 67% (Fuji 1) and 29%
      (Gold Label 1) did not follow the recommended ratios for luting purposes. The
      wide variations practiced in P/L mixing ratios against the recommended ratio for
      restorative purpose (approximately 1:2) and that for luting purpose (~1:1 to 2:1)
      may affect the performance characteristics of the material.

PMID- 19576163
TI  - Nasoendoscopic surgery in ophthalmology.

PMID- 19576164
TI  - Difference in virulence between Staphylococcus aureus isolates causing gangrenous
      mastitis versus subclinical mastitis in a dairy sheep flock.
AB  - Staphylococcus aureus mastitis in dairy sheep ranges from subclinical mastitis to
      lethal gangrenous mastitis. Neither the S. aureus virulence factors nor the host
      factors or the epidemiological events contributing to the different outcomes are
      known. In a field study in a dairy sheep farm over 21 months, 16 natural isolates
      of S. aureus were collected from six subclinical mastitis cases, one lethal
      gangrenous mastitis case, nasal carriage from eight ewes and one isolate from
      ambient air in the milking room. A genomic comparison of two strains, one
      responsible for subclinical mastitis and one for lethal gangrenous mastitis, was
      performed using multi-strain DNA microarrays. Multiple typing techniques (pulsed
      field-gel-electrophoresis, multiple-locus variable-number, single-nucleotide
      polymorphisms, randomly amplified polymorphic DNA, spa typing and sas typing)
      were used to characterise the remaining isolates and to follow the persistence of
      the gangrenous isolate in ewes' nares. Our results showed that the two strains
      were genetically closely related and they shared 3 615 identical predicted open
      reading frames. However, the gangrenous mastitis isolate carried variant versions
      of several genes (sdrD, clfA-B, sasA, sasB, sasD, sasI and splE) and was missing
      fibrinogen binding protein B (fnbB) and a prophage. The typing results showed
      that this gangrenous strain emerged after the initial subclinical mastitis
      screening, but then persisted in the flock in the nares of four ewes. Although we
      cannot dismiss the role of host susceptibility in the clinical events in this
      flock, our data support the hypothesis that S. aureus populations had evolved in
      the sheep flock and that S. aureus genetic variations could have contributed to
      enhanced virulence.

PMID- 19576165
TI  - Development of an amperometric assay for phosphate ions in urine based on a
      chemically modified screen-printed carbon electrode.
AB  - An amperometric assay for the determination of inorganic phosphate (Pi) in urine
      has been developed without the need for sample preparation. A screen-printed
      carbon electrode modified with the electrocatalyst cobalt phthalocyanine (CoPC
      SPCE) and covered with a cellulose acetate membrane (CAM) serves as the sensor.
      The sensor detects hydrogen peroxide (H(2)O(2)), which is produced as a result of
      the oxidative decarboxylation of pyruvate, catalyzed by pyruvate oxidase (PyOd),
      in the presence of Pi, oxygen, and cofactors. Following optimization of solution
      conditions, and in the presence of a urine sample, a linear range was found to
      exist between the rate of current increase and phosphate concentration over the
      range of 2.27 x 10(-5) to 1.81 x 10(-4)M, and the limit of detection was found to
      be 4.27 x 10(-6)M. The assay was applied to the determination of phosphate ions
      in the urine of a normal subject, and the mean concentration in unspiked urine
      was found to be 3.40 x 10(-5)M with a coefficient of variation of 8.0% (n=5). The
      mean recovery of phosphate added to urine samples was 98.7% with a coefficient of
      variation of 5.5% (n=3). To the authors' knowledge, this is the first report of
      an amperometric assay for Pi that incorporates a CoPC-SPCE as the sensing device.

PMID- 19576167
TI  - Photochemical and photoelectrochemical quenching of chlorophyll fluorescence in
      photosystem II.
AB  - This paper deals with kinetics and properties of variable fluorescence in leaves
      and thylakoids upon excitation with low intensity multi-turnover actinic light
      pulses corresponding with an excitation rate of about 10 Hz. These show a
      relatively small and amply documented rise in the sub-s time range towards the
      plateau level F(pl) followed by a delayed and S-shaped rise towards a steady
      state level F(m) which is between three and four fold the initial dark
      fluorescence level F(o). Properties of this retarded slow rise are i) rate of
      dark recovery is (1-6 s)(-1), ii) suppression by low concentration of
      protonophores, iii) responsiveness to complementary single turnover flash
      excitation with transient amplitude towards a level F(m) which is between five
      and six fold the initial dark fluorescence level F(o) and iv) in harmony with and
      quantitatively interpretable in terms of a release of photoelectrochemical
      quenching controlled by the trans-thylakoid proton pump powered by the light
      driven Q cycle. Data show evidence for a sizeable fluorescence increase upon
      release of (photo) electrochemical quenching, defined as qPE. Release of qPE
      occurs independent of photochemical quenching defined here as qPP even under
      conditions at which qPP = 1. The term photochemical quenching, hitherto
      symbolized by qP, will require a new definition, because it incorporates in its
      present form a sizeable photoelectrochemical component. The same is likely to be
      true for definition and use of qN as an indicator of non photochemical quenching.

PMID- 19576166
TI  - Mitochondrial calcium and the permeability transition in cell death.
AB  - Dysregulation of Ca(2+) has long been implicated to be important in cell injury.
      A Ca(2+)-linked process important in necrosis and apoptosis (or necrapoptosis) is
      the mitochondrial permeability transition (MPT). In the MPT, large conductance
      permeability transition (PT) pores open that make the mitochondrial inner
      membrane abruptly permeable to solutes up to 1500 Da. The importance of Ca(2+) in
      MPT induction varies with circumstance. Ca(2+) overload is sufficient to induce
      the MPT. By contrast after ischemia-reperfusion to cardiac myocytes, Ca(2+)
      overload is the consequence of bioenergetic failure after the MPT rather than its
      cause. In other models, such as cytotoxicity from Reye-related agents and storage
      reperfusion injury to liver grafts, Ca(2+) appears to be permissive to MPT onset.
      Lastly in oxidative stress, increased mitochondrial Ca(2+) and ROS generation act
      synergistically to produce the MPT and cell death. Thus, the exact role of Ca(2+)
      for inducing the MPT and cell death depends on the particular biologic setting.

PMID- 19576168
TI  - Long N-acyl fatty acids on sphingolipids are responsible for miscibility with
      phospholipids to form liquid-ordered phase.
AB  - The structure and thermotropic phase behaviour of aqueous dispersions of
      dipalmitoylphosphatidylcholine and glucosylceramide rich in C-24 fatty acyl
      residues was investigated by synchrotron X-ray diffraction methods. Binary
      mixtures comprised of molar ratios 2.5:100, 6.5:100, 12.6:100, 25:100, 40:100 and
      50:100, glucolipid:phospholipid were examined in heating and cooling scans of 2
      degrees /min between 25 and 85 degrees C. Small-angle reflections indicated
      coexisting lamellar structures over the entire temperature range investigated.
      Reversible thermotropic changes were observed in one lamellar structure that is
      consistent with transitions between gel, ripple and fluid lamellar phases of pure
      phospholipid. The temperature of these transitions, however, were progressively
      shifted up by about 5 degrees C in the mixture containing the highest proportion
      of glucolipid and coincided with a published endothermic peak observed in this
      mixture. A higher-temperature endotherm was associated with molecular
      rearrangements on transition of the gel phase phospholipid to the fluid phase.
      This rearrangement was associated with the appearance of identifiable transient
      intermediate structures in the small-angle scattering region. The glucolipid
      formed stoichiometric mixtures with the phospholipid at all temperatures
      investigated and there was no evidence of phase separation of pure glucolipid.
      Analysis of the wide-angle scattering profiles during an initial heating scan of
      a binary mixture comprised of 40:60 glucolipid:phospholipid was consistent with a
      phase transition of pure phospholipid at about 43 degrees C coexisting with a
      liquid-ordered phase formed from the two lipids. This was confirmed by analysis
      of the small-angle scattering peaks of this mixture recorded at 25 and 65 degrees
      C which showed that a glucolipid-rich phase coexisted with almost pure bilayers
      of phospholipid at both temperatures. The glucolipid-rich phase consisted of
      45:55 mole ratio glucolipid:phospholipid at 25 degrees C with pure phospholipid
      in gel phase and 42:58 mole ratio at 65 degrees C when the phospholipid was in
      the fluid phase. The results are discussed with reference to the role of the
      length of the N-acyl substituent of the sphingolipids in formation of complexes
      with phospholipids.

PMID- 19576169
TI  - Familial amyotrophic lateral sclerosis-linked mutant SOD1 aberrantly interacts
      with tubulin.
AB  - Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause 20-25% of familial
      amyotrophic lateral sclerosis (ALS). Mutant SOD1 causes motor neuron degeneration
      through toxic gain-of-function(s). However, the direct molecular targets of
      mutant SOD1, underlying its toxicity, are not fully understood. In this study, we
      found that alpha/beta-tubulin is one of the major mutant SOD1-interacting
      proteins, but that wild-type SOD1 does not interact with it. The interaction
      between tubulin and mutant SOD1 was detected in the spinal cords of mutant G93A
      SOD1 transgenic mice before the onset of symptoms. Tubulin interacted with amino
      acid residues 1-23 and 116-153 of SOD1. Overexpression of mutant SOD1 resulted in
      the accumulation of tubulin in detergent-insoluble fractions. In a cell-free
      system, mutant SOD1 modulated tubulin polymerization, while wild-type SOD1 did
      not. Since tightly regulated microtubule dynamics is essential for neurons to
      remain viable, alpha/beta-tubulin could be an important direct target of mutant
      SOD1.

PMID- 19576170
TI  - Attenuation of hepatic expression and secretion of selenoprotein P by metformin.
AB  - High serum selenium levels have been associated epidemiologically with increased
      incidence of type 2 diabetes. The major fraction of total selenium in serum is
      represented by liver-derived selenoprotein P (SeP). This study was undertaken to
      test for a hypothesized effect of hyperglycemia and the antihyperglycemic drug
      metformin on hepatic selenoprotein P biosynthesis. Cultivation of rat hepatocytes
      in the presence of high glucose concentrations (25 mmol/l) resulted in increased
      selenoprotein P mRNA expression and secretion. Treatment with metformin dose
      dependently downregulated SeP mRNA expression and secretion, and suppressed
      glucocorticoid-stimulated production of SeP. Moreover, metformin strongly
      decreased mRNA levels of selenophosphate synthetase 2 (SPS-2), an enzyme
      essential for selenoprotein biosynthesis. Taken together, these results indicate
      an influence of metformin on selenium metabolism in hepatocytes. As selenoprotein
      P is the major transport form of selenium, metformin treatment may thereby
      diminish selenium supply to extrahepatic tissues.

PMID- 19576171
TI  - Essential role of Nrf2 in keratinocyte protection from UVA by quercetin.
AB  - Much of the cell injury caused by ultraviolet A (UVA) irradiation is associated
      with oxidative stress. Quercetin is a major natural polyphenol that is known to
      protect cells from UVA-induced damage. Here, we investigated the molecular
      mechanism of this protection. Quercetin pretreatment strongly suppressed UVA
      induced apoptosis in human keratinocyte HaCaT cells, markedly increased protein
      levels of the transcription factor Nrf2, induced the expression of antioxidative
      genes, and dramatically reduced the production of reactive oxygen species
      following UVA irradiation. Importantly, these beneficial effects were greatly
      attenuated by downregulating Nrf2 expression. Thus, quercetin protects cells from
      UVA damage mainly by elevating intracellular antioxidative activity via the
      enhanced accumulation of a transcription factor for antioxidant genes, Nrf2.

PMID- 19576172
TI  - Deregulated expression of E2F1 promotes proteolytic degradation of tumor
      suppressor p73 and inhibits its transcriptional activity.
AB  - The expression of tumor suppressor p73 is regulated at mRNA and protein levels.
      It has been shown that E2F1 acts as a transcriptional activator for p73. In this
      study, we have found that deregulated expression of E2F1 increases the mRNA level
      of p73, however, E2F1 promotes the degradation of p73. Immunoprecipitation
      experiments demonstrated that E2F1 forms a complex with p73 and inhibits the
      transcriptional activity of p73. Enforced expression of E2F1 induces degradation
      of p73 in a proteasome-independent manner. Additionally, the deletion analysis
      showed that E2F1(1-117) has an undetectable effect on p73, whereas E2F1(1-285)
      and E2F1(1-414) have an ability to promote degradation of p73 and inhibition of
      p73 transcriptional activity, suggesting that the region of E2F1 between amino
      acid residues 118 and 285 has a critical role in the regulation of p73. Taken
      together, our present study indicates that E2F1 has a dual role in the regulation
      of p73.

PMID- 19576173
TI  - Pharmacological characterization of INCB3344, a small molecule antagonist of
      human CCR2.
AB  - The chemokine receptor 2 (CCR2) directs migration of monocytes and has been
      proposed to be a drug target for chronic inflammatory diseases. INCB3344 was
      first published as a small molecule nanomolar inhibitor of rodent CCR2. Here, we
      show that INCB3344 can also bind human CCR2 (hCCR2) with high affinity, having a
      dissociation constant (K(d)) of approximately 5nM. The binding of the compound to
      the receptor is rapid and reversible. INCB3344 potently inhibits hCCR2 binding of
      monocyte chemoattractant protein-1 (MCP-1) and MCP-1-induced signaling and
      function in hCCR2-expressing cells, including ERK phosphorylation and chemotaxis,
      and is competitive against MCP-1 in vitro. INCB3344 also blocks MCP-1 binding to
      monocytes in human whole blood, with potency consistent with in vitro studies.
      The whole blood binding assay described here can be used for monitoring
      pharmacodynamic activity of CCR2 antagonists in both preclinical models and in
      the clinic.

PMID- 19576174
TI  - PtdIns5P protects Akt from dephosphorylation through PP2A inhibition.
AB  - Phosphatidylinositol 5-phosphate (PtdIns5P), the most recently discovered
      phosphoinositide, has been proposed to play a role as a lipid mediator of
      intracellular signaling. We have previously shown that PtdIns5P generated by
      IpgD, an effector of the causative agent of dysentery Shigella flexneri,
      activates the PI 3-kinase/Akt pathway. Here, we demonstrate that PtdIns5P is able
      to protect Akt from dephosphorylation. This effect is not due to inhibition of
      the phosphoinositide phosphatase regulating PtdIns(3,4,5)P(3) levels PTEN but
      rather to PtdIns5P-induced phosphorylation and subsequent inhibition of the
      catalytic subunit of PP2A phosphatases. These data shed light on a new mechanism
      used by S. flexneri bacteria to sustain Akt activation to increase survival of
      the host cells during bacterial replication.

PMID- 19576175
TI  - Dihydroavenanthramide D protects pancreatic beta-cells from cytokine and
      streptozotocin toxicity.
AB  - Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring
      avenanthramide, which is the active component of oat. Although its anti
      inflammatory, antiatherosclerotic, and antioxidant effects have been reported,
      the effect of DHAvD on type 1 diabetes is unknown. Therefore, in this study, the
      effect of DHAvD on cytokine- or streptozotocin-induced beta-cell damage was
      investigated. Treatment of RINm5F insulinoma cells or isolated islets with IL
      1beta and IFN-gamma induced beta-cell damage through a NF-kappaB-dependent
      signaling pathway. DHAvD-pretreated RINm5F cells or islets showed resistance to
      cytokine toxicity, namely suppressed nitric oxide (NO) production, reduced the
      inducible form of NO synthase expression, and decreased beta-cell destruction and
      the normal insulin secretion capacity. Furthermore, pretreatment with DHAvD
      blocked the development of type 1 diabetes in streptozotocin-treated mice. Prior
      injection with DHAvD maintained a normal range of plasma glucose and insulin, and
      retained immunoreactivity for insulin in the pancreas. These results suggest that
      DHAvD may be used to preserve functional beta-cell mass.

PMID- 19576176
TI  - Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease
      implications.
AB  - Mutations in the alpha synuclein gene (SNCA) are the most potent cause of
      autosomal dominant Parkinson disease (PD) while mutations in the leucine-rich
      repeat kinase 2 (LRRK2) gene are the most common cause. We hypothesized that a
      direct interaction may exist between their protein products. Here we show that
      full-length Lrrk2 or fragments containing its kinase domain have a significant
      capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such
      phosphorylated Asyn is the major component of pathological deposits in PD. We
      further show that the G2019S mutation in Lrrk2, which is the most common genetic
      determinant of PD, has a significantly greater capacity than wild-type Lrrk2 to
      phosphorylate Asyn. This suggests that the G2019S mutant protein may cause PD by
      generating pathological levels of phosphorylated Asyn. Controlling Lrrk2 Asyn
      phosphokinase activity may be an approach to disease modifying therapy for PD and
      other synucleinopathies.

PMID- 19576177
TI  - Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production
      by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose via blockade of NF-kappaB and STAT1
      activation in the HaCaT cells.
AB  - Keratinocytes, one of major cell types in the skin, can be induced by TNF-alpha
      and IFN-gamma to express thymus- and activation-regulated chemokine (TARC/CCL17),
      which is considered to be a pivotal mediator in the inflammatory responses during
      the development of inflammatory skin diseases, such as atopic dermatitis (AD). In
      this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-beta-d-glucose
      (PGG), isolated from the barks of Juglans mandshurica, on TNF-alpha/IFN-gamma
      induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment
      of HaCaT cells with PGG suppressed TNF-alpha/IFN-gamma-induced protein and mRNA
      expression of CCL17. PGG significantly inhibited TNF-alpha/IFN-gamma-induced NF
      kappaB activation as well as STAT1 activation. Furthermore, pretreatment with PGG
      resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT
      cells treated with IFN-gamma. These results suggest that PGG may exert anti
      inflammatory responses by suppressing TNF-alpha and/or IFN-gamma-induced
      activation of NF-kappaB and STAT1 in the keratinocytes and might be a useful tool
      in therapy of skin inflammatory diseases.

PMID- 19576178
TI  - Frequent promoter hypermethylation and transcriptional downregulation of BTG4
      gene in gastric cancer.
AB  - The BTG4 gene belongs to the BTG family of genes endowed with antiproliferative
      properties. In this study, we have found that BTG4 undergoes promoter CpG island
      hypermethylation-associated inactivation in gastric cancer and 5'-aza-2'
      deoxycytidine (DAC) treatment restores BTG4 expression. We also found BTG4 levels
      were significantly reduced in primary gastric cancer but not in normal gastric
      tissues. BTG4 reexpression in gastric cancer causes growth inhibition of colony
      assays and nude mice. Taken together, our data support BTG4 as a candidate tumor
      suppressor gene that is epigenetically silenced in the majority of gastric
      cancers.

PMID- 19576179
TI  - Enzymatic properties of cytochrome P450 catalyzing 3'-hydroxylation of naringenin
      from the white-rot fungus Phanerochaete chrysosporium.
AB  - We cloned full-length cDNAs of more than 130 cytochrome P450s (P450s) derived
      from Phanerochaete chrysosporium, and successfully expressed 70 isoforms using a
      co-expression system of P. chrysosporium P450 and yeast NADPH-P450 reductase in
      Saccharomyces cerevisiae. Of these P450s, a microsomal P450 designated as
      PcCYP65a2 consists of 626 amino acid residues with a molecular mass of 68.3kDa.
      Sequence alignment of PcCYP65a2 and human CYP1A2 revealed a unique structure of
      PcCYP65a2. Functional analysis of PcCYP65a2 using the recombinant S. cerevisiae
      cells demonstrated that this P450 catalyzes 3'-hydroxylation of naringenin to
      yield eriodictyol, which has various biological and pharmacological properties.
      In addition, the recombinant S. cerevisiae cells expressing PcCYP65a2 metabolized
      such polyaromatic compounds as dibenzo-p-dioxin (DD), 2-monochloroDD, biphenyl,
      and naphthalene. These results suggest that PcCYP65a2 is practically useful for
      both bioconversion and bioremediation.

PMID- 19576180
TI  - Nicotinic acetylcholine receptors as therapeutic targets: emerging frontiers in
      basic research and clinical science--editorial perspective.

PMID- 19576182
TI  - Insight in nAChR subtype selectivity from AChBP crystal structures.
AB  - Nicotinic acetylcholine receptors (nAChRs) display a broad variety of subtypes,
      which in turn present a complex subcellular and regional expression pattern in
      the brain, as well as a specific pharmacological profile. The association of
      these nAChRs with different types of brain disease has turned them into
      interesting drug targets for the treatment of Alzheimer's disease or
      schizophrenia, or for anti-smoking compounds among others. In the same way,
      muscle-type nAChRs present at neuromuscular junctions are also being targeted by
      muscle relaxants. However, to date no high-resolution structural data are
      available on functional pentameric forms of membrane-bound nicotinic receptors.
      Therefore, characterization of the selectivity profiles of different nicotinic
      receptor subtypes, enabling efficient drug design, is a serious issue. Over the
      last eight years various high-resolution structures of acetylcholine binding
      protein (AChBP), which is homologous to the extracellular ligand-binding domain
      of the nicotinic acetylcholine receptor, have been obtained. AChBPs in complex
      with different ligands have provided detailed insight into the neurotransmitter
      binding site of nicotinic acetylcholine receptors. We present here the various
      efforts towards rationalizing subtype specificity in these receptors through the
      structural studies of acetylcholine binding protein-ligand complexes.

PMID- 19576181
TI  - GTS-21 inhibits pro-inflammatory cytokine release independent of the Toll-like
      receptor stimulated via a transcriptional mechanism involving JAK2 activation.
AB  - The vagus nerve can limit inflammation via the alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR). Selective pharmacological stimulation of the alpha7nAChR
      may have therapeutic potential for the treatment of inflammatory conditions. We
      determined the anti-inflammatory potential of GTS-21, an alpha7nAChR-selective
      partial agonist, on primary human leukocytes and compared it with nicotine, the
      nAChR agonist widely used for research into the anti-inflammatory effects of
      alpha7nAChR stimulation. Furthermore, we investigated whether the effects of both
      nicotinic agonists were restricted to specific Toll-like receptors (TLRs)
      stimulated and explored the mechanism behind the anti-inflammatory effect of GTS
      21. GTS-21 and nicotine inhibited the release of pro-inflammatory cytokines in
      peripheral blood mononuclear cells (PBMCs), monocytes and whole blood independent
      of the TLR stimulated, with higher potency/efficacy for GTS-21 compared to
      nicotine. The anti-inflammatory cytokine IL-10 was relatively unaffected by both
      nicotinic agonists. The effects of GTS-21 and nicotine could not be reversed by
      nAChR antagonists, while the JAK2 inhibitor AG490 abolished the anti-inflammatory
      effects. GTS-21 downregulated monocyte cell-surface expression of TLR2, TLR4 and
      CD14. qPCR analysis demonstrated that the anti-inflammatory effect of GTS-21 is
      mediated at the transcriptional level and involves JAK2-STAT3 activation. In
      conclusion, GTS-21 has a profound anti-inflammatory effect in human leukocytes
      and that GTS-21 is more potent/efficacious than nicotine. The absence of a
      blocking effect of nAChR antagonists in human leukocytes might indicate different
      pharmacological properties of the alpha7nAChR in human leukocytes compared to
      other cell types. GTS-21 may be promising from a therapeutic perspective because
      of its suitability for human use.

PMID- 19576184
TI  - PPARalpha activator fenofibrate modulates angiotensin II-induced inflammatory
      responses in vascular smooth muscle cells via the TLR4-dependent signaling
      pathway.
AB  - Angiotensin II (Ang II) is a crucial contributor to inflammatory processes
      involved in development and progression of atherosclerotic lesion. Toll-like
      receptor 4 (TLR4) signaling responsible for the initiation of inflammation also
      participates in pathogenesis of atherosclerosis. The protective effect of
      peroxisome proliferator-activated receptor alpha (PPARalpha) activators on
      atherosclerosis may be due to their impact on vascular inflammation, plaque
      instability and thrombosis. However, mechanisms underlying the inhibitory effects
      of PPARalpha activators on Ang II-induced vascular inflammation and the TLR4
      dependent signaling pathway involved in vascular smooth muscle cells (VSMCs)
      remain unclear. The present study demonstrated that PPARalpha activator
      fenofibrate decreased Ang II-induced generation of pro-inflammatory mediators
      such as TLR4, MMP-9 and TNF-alpha, but enhanced production of anti-inflammatory
      molecules like PPARalpha and 6-keto-PGF(1alpha) both in vivo and in vitro.
      Meanwhile, treatment of VSMCs with the TLR4 inhibitor or TLR4 siRNA showed that
      the inhibitory effects of fenofibrate on Ang II-induced inflammatory responses in
      VSMCs were dependent on TLR4. Furthermore, fenofibrate depressed Ang II-induced
      inflammatory responses in VSMCs by intervening the downstream effector molecules
      of the TLR4-dependent signaling pathway, including interferon-gamma inducible
      protein 10 (IP-10), protein kinases C (PKC) and nuclear factor kappaB (NF
      kappaB). Thus, these findings provide the evidence for beneficial effects of
      PPARalpha activator fenofibrate to counter-regulate vascular inflammation induced
      by Ang II. More importantly, anti-inflammatory action of fenofibrate via
      interfering with the TLR4-dependent signaling pathway (TLR4/IP-10/PKC/NF-kappaB)
      works in concert to protect against atherosclerosis.

PMID- 19576183
TI  - Interference with endothelial cell function by JG-03-14, an agent that binds to
      the colchicine site on microtubules.
AB  - JG-03-14, a novel tetrasubstituted pyrrole with microtubule-depolymerizing and
      anti-proliferative activities, was tested for its effect on endothelial cell (EC)
      functions in vitro. JG-03-14 was a potent inhibitor of EC vessel-like tube
      formation on extracellular matrix (IC(50) of 40nM) and caused the involution of
      established vessels, potential anti-angiogenic and vascular-disrupting
      activities, respectively. These actions were not due to the inhibition of EC
      proliferation or to the induction of apoptosis by JG-03-14. While similar effects
      were observed with the microtubule-depolymerizing and vascular-disrupting drug
      combretastatin-A4 (CoA4), JG-03-14 had a more selective effect on tube formation,
      relative to its cytotoxic actions, than did CoA4. Potential molecular mechanisms
      for JG-03-14's anti-vascular actions were explored. In contrast to the taxanes,
      which also have anti-vascular actions, JG-03-14 did not disrupt focal adhesion
      formation or block VEGF-induced phosphorylation of focal adhesion kinase. It did,
      however, inhibit VEGF-induced phosphorylation of VE-cadherin and reduce the
      association of beta-catenin with VE-cadherin. It caused cell retraction,
      intercellular gaps, and abnormally elongated adherens junctions at low
      concentrations, and prominent, but reversible, plasma membrane blebbing at higher
      concentrations. These results suggest that JG-03-14 may affect vascular
      morphogenesis by disrupting the interaction of adjacent endothelial cells,
      possibly as a consequence of effects on VE-cadherin, beta-catenin, and/or actin.
      They also provide the first report of anti-vascular activity for this class of
      compounds.

PMID- 19576185
TI  - 15-Deoxi-Delta(12,14)-prostaglandin J2 is a tubulin-binding agent that
      destabilizes microtubules and induces mitotic arrest.
AB  - 15-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play an
      important role in the pathophysiology of carcinogenesis, however, the molecular
      mechanisms underlying these effects are not yet fully understood. Recently, we
      have shown that 15d-PGJ(2) is a potent inducer of breast cancer cell death and
      that this effect is associated with a disruption of the microtubule cytoskeletal
      network. Here, we show that treatment of the MCF-7 breast cancer cell line with
      15d-PGJ(2) induces an accumulation of cells in the G(2)/M compartment of the cell
      cycle and a marked disruption of the microtubule network. 15d-PGJ(2) treatment
      causes mitotic abnormalities that consist of failure to form a stable metaphase
      plate, incapacity to progress through anaphase, and failure to complete
      cytokinesis. 15d-PGJ(2) binds to tubulin through the formation of a covalent
      adduct with at least four cysteine residues in alpha- and beta-tubulin, as
      detected by hybrid triple-quadrupole mass spectrometry analysis. Overall, these
      results support the hypothesis that microtubule disruption and mitotic arrest, as
      a consequence of the binding of 15d-PGJ(2) to tubulin, can represent one
      important pathway leading to breast cancer cell death.

PMID- 19576186
TI  - Mechanisms of anti-cancer action and pharmacology of clofarabine.
AB  - Clofarabine, a next-generation deoxyadenosine analogue, was developed on the
      basis of experience with cladribine and fludarabine in order to achieve higher
      efficacy and avoid extramedullary toxicity. During the past decade this is the
      only drug granted approval for treatment of pediatric acute leukemia. Recent
      clinical studies have established the efficacy of clofarabine in treating
      malignancies with a poor prognosis, such as adult, elderly, and relapsed
      pediatric leukemia. The mechanisms of its anti-cancer activity involve a
      combination of direct inhibition of DNA synthesis and ribonucleotide reductase
      and induction of apoptosis. Due to this broad cytotoxicity, this drug is
      effective against various subtypes of leukemia and is currently being tested as
      an oral formulation and for combination therapy of both leukemias and solid
      tumors. In this review we summarize current knowledge pertaining to the molecular
      mechanisms of action and pharmacological properties of clofarabine, as well as
      clinical experiences with this drug with the purpose of facilitating the
      evaluation of its efficacy and the development of future therapies.

PMID- 19576187
TI  - Involvement of mTOR kinase in cytokine-dependent microglial activation and cell
      proliferation.
AB  - Neuroinflammation plays a prominent role in the pathophysiology of several
      neurodegenerative disorders, including Multiple Sclerosis. Reactive microglial
      cells are always found in areas of active demyelination as well as in normal
      appearing white matter. Microglia contribute to initiating and maintaining brain
      inflammation, and once activated release pro-inflammatory mediators potentially
      cytotoxic, like nitric oxide (NO). It is now evident that the mTOR signaling
      pathway regulates different functions in the innate immune system, contributing
      to macrophage activation. More recently, mTOR has been found to enhance the
      survival of EOC2 microglia during oxygen-glucose deprivation and increase NO
      synthase 2 (NOS2) expression during hypoxia in BV2 microglial cell line, thus
      suggesting an involvement in microglial pro-inflammatory activation. In the
      present study, we detected mTOR activation in response to two different stimuli,
      namely LPS and a mixture of cytokines, in primary cultures of rat cortical
      microglia. Moreover, mTOR inhibitors reduced NOS activity and NOS2 expression
      induced by cytokines, but not those induced by LPS. The mTOR inhibitor RAD001, in
      combination with cytokines, also reduced microglial proliferation and the
      intracellular levels of cyclooxygenase. Under basal conditions mTOR inhibition
      significantly reduced microglial viability. Interestingly, mTOR inhibitors did
      not display any relevant effect on astrocyte NOS2 activity or cell viability. In
      conclusion, mTOR selectively controls microglial activation in response to pro
      inflammatory cytokines and appears to play a crucial role in microglial
      viability; thus these drugs may be a useful pharmacological tool to reduce
      neuroinflammation.

PMID- 19576188
TI  - Hemoglobin crystals: a pro-inflammatory potential confounder of rat experimental
      intracerebral hemorrhage.
AB  - In vivo rat hemoglobin crystallization has been reported in lung, liver and
      kidney, but never following central nervous system injury. In the present study,
      we examined hemoglobin crystallization following experimental intracerebral
      hemorrhage (ICH) and its effects on inflammation. Ninety-one rat brains,
      subjected to either autologous or collagenase ICH, and vehicle controls, were
      retrospectively examined. In both models, hemoglobin crystals were present in
      most brains at 24 and 48 h. They were especially prominent at 24 h in autologous
      ICH brains (2.5% of the hematoma vs 0.6% in collagenase animals; p=0.0001) and,
      at 5 h, were only present in autologous ICH brains. Crystals were diminishing at
      48 h and were absent at 7 days. Crystals appeared in clusters around blood
      vessels. In both models, at 24 h, crystals appeared strongly chemotactic for
      neutrophils. This effect was most pronounced in autologous ICH brains (2628+/-182
      neutrophils/mm(2) hematoma crystals vs 327+/-54 neutrophils/mm(2) hematoma;
      p<0.0001). In these animals up to 30% of the total neutrophilic infiltrate was
      located around crystals. A greater overall neutrophilic infiltrate was seen in
      autologous ICHs with higher percentages of crystalline hemoglobin (p=0.04 for
      trend). Although hemoglobin crystallization occurs in both models of ICH, it is
      particularly prominent following autologous ICH. Accordingly, hemoglobin
      crystallization may exaggerate the importance of inflammation in this model.

PMID- 19576189
TI  - Subcellular localization of the carbohydrate Lewis(x) adhesion structure in
      hippocampus cell cultures.
AB  - The Lewis(x) (Le(x)) epitope (Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc-R) has been
      associated with the development of the central nervous system of diverse species
      including human and rodents. In this work, Le(x) has been found in the tetanus
      neurotoxin insensitive vesicle-associated membrane protein (TI-VAMP) compartment
      of rat hippocampus neurons in culture, at 7 days in vitro (DIV), when neurite
      extension is abundant. The TI-VAMP compartment is known to be associated with
      neurite outgrowth. Le(x) was found predominantly in neurites but also in somata
      and in growth cones. Abundant Le(x)-carrier glycoproteins specific to neurons
      have been identified at this stage of differentiation. At a later stage of
      differentiation, at 14 DIV, Le(x) appeared in extrasynaptic sites of GABAergic
      neurons, and in synaptic sites of glutamatergic neurons.

PMID- 19576191
TI  - Cytotoxicity of methoctramine and methoctramine-related polyamines.
AB  - Methoctramine and its analogues are polymethylene tetramines that selectively
      bind to a variety of receptor sites. Although these compounds are widely used as
      pharmacological tools for receptor characterization, the toxicological properties
      of these polyamine-based structures are largely unknown. We have evaluated the
      cytotoxic effects of methoctramine and related symmetrical analogues differing in
      polymethylene chain length between the inner nitrogens against a panel of cell
      lines. Methoctramine caused cell death only at high micromolar concentrations,
      whereas its pharmacological action is exerted at nanomolar level. Increasing the
      spacing between the inner nitrogen atoms resulted in a significative increase in
      cytotoxicity. In particular, an elevated cytotoxicity is associated to a
      methylene chain length of 12 units dividing the inner amine functions (compound
      5). H9c2 cardiomyoblasts were the most sensitive cells, followed by SH-SY5Y
      neuroblastoma, whereas HL60 leukaemia cells were much more resistant.
      Methoctramine and related compounds down-regulated ornithine decarboxylase, the
      first enzyme of polyamine biosynthesis even at non-toxic concentration. Further,
      methoctramine and compound 5 caused a limited up-regulation of
      spermine/spermidine N-acetyltransferase, suggesting that interference in
      polyamine metabolism is not a primary mechanism of toxicity. Methoctramine and
      its analogues bound to DNA with a higher affinity than spermine, but the
      correlation with their toxic effect was poor. The highly toxic compound 5 killed
      the cells in the absence of caspase activation and caused an increase in p53
      expression and ERK1/2 phosphorylation. Compound 5 was directly oxidized by cell
      homogenates producing hydrogen peroxide and its toxic effect was partially
      subdued by the inhibition of its uptake, by the NMDA ligand MK-801, and by the
      antioxidant N-acetylcysteine, suggesting that compound 5 can act at different
      cellular levels and lead to oxidative stress.

PMID- 19576190
TI  - Isolation, characterization and antioxidative effect of phyllanthin against CCl4
      induced toxicity in HepG2 cell line.
AB  - The present study was an attempt to investigate the hepatoprotective and
      antioxidative property of Phyllanthus amarus (P. amarus) extract and phyllanthin.
      Phyllanthin, one of the active lignin present in this plant species was isolated
      from the aerial parts, by silica gel column chromatography employing gradient
      elution with hexane-ethyl acetate solvent mixture. It was obtained in high yields
      (1.23%), compared to reported procedures and the purity was ascertained by HPTLC
      and reversed-phase HPLC analysis. Characterization of phyllanthin was done by mp,
      UV-Visible spectrophotometry, elemental analysis, FT-IR, 1H NMR, 13C NMR and mass
      spectral analysis. Free radical scavenging activity of P. amarus extract and
      phyllanthin was also examined using DPPH assay. The protective effect of P.
      amarus extract and phyllanthin was studied on CCl4-induced toxicity in human
      hepatoma HepG2 cell line. The results indicated that CCl4 treatment caused a
      significant decrease in cell viability. In addition, the toxin treatment
      initiated lipid peroxidation (LPO), caused leakage of enzymes like alanine
      transaminase (ALT) and lactate dehydrogenase (LDH) with a significant decrease in
      glutathione (GSH) levels. It was observed that phyllanthin effectively alleviated
      the changes induced by CCl4 in a concentration-dependent manner, with much
      smaller strengths as compared to P. amarus extract.

PMID- 19576192
TI  - NaCl-dependent formation of the highly crystalline phase in sufficiently hydrated
      dimyristoylphosphatidylglycerol bilayers.
AB  - We investigated the low-temperature phase behavior of
      dimyristoylphosphatidylglycerol (DMPG) bilayers in the presence of high
      concentration of NaCl (>or=100 mM). Differential scanning calorimetry showed that
      the highly crystalline (HC) phase grew after an initial delay period when DMPG
      bilayers were sufficiently hydrated and incubated at 1 degree C in the presence
      of more than 100 mM NaCl. The HC phase formation reached a plateau, the level of
      which depended on NaCl concentration; all the lipids were unable to be in the HC
      phase at the plateau stage without a quite high concentration of NaCl. Since
      electron microscopic observations suggested that the HC phase formed coexists
      with the precursor phases in a closed vesicle, elastic constrain and/or shortage
      of free sodium ions in the inside of the closed vesicle may prevent the complete
      transition into the HC phase.

PMID- 19576193
TI  - Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow
      up of antithyroid drug treated Graves' disease: comparison with the second
      generation human TRAb assay.
AB  - BACKGROUND: We compared the clinical performances of two new M22-based assays for
      TSH-receptor antibody (TRAb) with those of the human TRAb assay (hTRAK) in
      Graves' disease patients at the end of treatment. PATIENTS AND METHODS: Sera were
      obtained from 128 Graves' patients treated for 18 months with antithyroid drugs.
      Sixty-six remained in remission and sixty-two had relapse of hyperthyroidism in a
      3-year follow-up after discontinuing treatment. TRAbs were measured using two M22
      based methods (electrochemiluminescence using the Cobas or ELISA using the
      Medizym TRAb clone) and with the hTRAK. RESULTS: At T18, the results were
      significantly higher by the Cobas assay (median: 2.7 IU/L, range: 1.1-18.5 IU/L)
      or lower by ELISA (median: 0.56 IU/L, range: 0.22-14.8 IU/L) than those obtained
      for the hTRAK (median: 1.5 IU/L, range: 0.9-9.8 IU/L). The use of cut-off limits
      at 1.9 IU/L, 3.2 IU/L and 0.94 IU/L gave similar and higher prevalences of TRAb
      positive patients in the group of relapse as compared to the remission group.
      However, some patients remained misclassified in each remission or relapse group.
      CONCLUSIONS: The M22-based TRAb assays did not improve the predictive value of
      relapse obtained with the hTRAK measured at the end of treatment. High inter
      method variability requires assay harmonization for correct interpretation of
      results.

PMID- 19576194
TI  - TNF-alpha/IL-10 ratio and C-reactive protein as markers of the inflammatory
      response in CAD-prone North Indian patients with acute myocardial infarction.
AB  - BACKGROUND: Cytokines are responsible for the modulation of immunological and
      inflammatory processes and play a significant role in the pathogenesis of
      coronary artery disease (CAD). Tumor necrosis factor (TNF)-alpha is the major pro
      inflammatory cytokine while interleukin-10 (IL-10) is the major anti-inflammatory
      cytokine in patients with CAD. We determined the significance of the TNF/IL-10
      ratio and C-reactive protein (CRP) in patients of acute myocardial infarction as
      a marker for CAD in the atherosclerosis-prone North Indian population. METHODS:
      The study group comprised of 100 patients of acute myocardial infarction (AMI)
      and 100 age and sex matched healthy controls. Lipid profile, apolipoprotein-A
      (Apo-A), apolipoprotein-B (Apo-B) and CRP concentrations were estimated using
      commercially available kits in all patients and control subjects. TNF-alpha,
      lipoprotein (a) (Lp(a)) and IL-10 concentrations were assayed by using
      commercially available ELISA kits. RESULTS: The TNF-alpha concentrations were
      significantly higher in patients with acute myocardial infarction (86.9+/-4.7
      pg/ml), as compared to control subjects (7.1+/-0.67 g/ml). AMI patients also
      exhibited higher serum concentrations of IL-10 (5.74+/-0.82 pg/ml), in comparison
      to the controls (1.22+/-0.06 pg/ml). The ratio of TNF-alpha to IL-10 was
      significantly increased in cases (15.2+/-1.13), in comparison to healthy subjects
      (5.8+/-0.64). CONCLUSIONS: These cytokines underline the role of the immune
      processes during unstable atherosclerosis and in the pathogenesis of coronary
      artery disease in the Indian context.

PMID- 19576195
TI  - HIV-1 clade C infection and progressive disruption in the relationship between
      cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study.
AB  - BACKGROUND: It is well established that there is mutual interaction between the
      neuroendocrines and immune systems and that the disturbance in any one system
      could affect the function of the other. While there is a large body of evidence
      suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B)
      infection on both immune and neuroendocrine systems, the consequence of HIV-1
      clade C infection (with structural differences from HIV-1B virus) on these
      systems is not clearly understood. METHODS: We carried out a 2-year longitudinal
      study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS
      and their relationship with declining CD4+ cell counts in neurologically
      asymptomatic HIV-C infected individuals (N=84) in order to understand the impact
      of HIV-1 clade C infection on adrenocortical dysfunction and its relationship
      with the progressive decline in the cell mediated immunity. RESULTS: We found
      that while plasma cortisol levels increased significantly at baseline in HIV-1C
      infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83+/
      0.39 vs controls, 8.04+/-0.45; p<0.01), there was a significant decrease in DHEAS
      in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02+/-4.9 vs
      185.1+/-12.03, p<0.001), and consequently a significant increase in
      cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19+/-0.002 vs control
      0.058+/-0.006; p<0.001). Moreover, in HIV-1C infected individuals, there was a
      strong positive correlation between DHEAS and CD4 cells (r=0.2; p<0.05), and a
      strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and
      CD4 cells (r=-0.25; p<0.01; and r=-0.31; p<0.001, respectively). CONCLUSIONS:
      These findings suggest the persistent and progressive adrenocortical dysfunction
      during the asymptomatic phase of HIV infection, and that the evaluation of
      increase in plasma cortisol, a decrease in DHEAS, and an increase in
      cortisol:DHEAS ratio may serve as important biomarkers preceding the impending
      down regulation of CD4 cell counts and progressive decline in the immune system
      function in HIV-1C infection. Furthermore, these findings may indicate the
      dysregulation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, the
      enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone
      progesterone pathway, and that it may offer an opportunity for drug discovery
      targeting re-regulation of 3beta-HSD activity for potential therapeutic
      application in HIV-1C infection.

PMID- 19576196
TI  - Vitreous cryopreservation of tissue engineered bone composed of bone marrow
      mesenchymal stem cells and partially demineralized bone matrix.
AB  - Cryopreservation of tissue engineered products by maintaining their structure and
      function is a prerequisite for large-scale clinical applications. In this study,
      we examined the feasibility of cryopreservation of tissue engineered bone (TEB)
      composed of osteo-induced canine bone marrow mesenchymal stem cells (cBMSCs) and
      partially demineralized bone matrix (pDBM) scaffold by vitrification. A novel
      vitreous solution named as VS442 containing 40% dimethyl-sulfoxide (DMSO), 40%
      EuroCollins (EC) solution and 20% basic culture medium (BCM) was developed. After
      being cultured in vitro for 8 days, cell/scaffold complex in VS442 was subjected
      to vitreous preservation for 7 days and 3 months, respectively. Cell viability,
      proliferation and osteogenic differentiation of cBMSCs in TEB after vitreous
      cryopreservation were examined with parallel comparisons being made with those
      cryopreserved in VS55 vitreous solution. Compared with that cryopreserved in
      VS55, cell viability and subsequent proliferative ability of TEB in VS442 after
      being rewarmed were significantly higher as detected by live/dead staining and
      DNA assay. The level of alkaline phosphatase (ALP) expression and osteocalcin
      (OCN) deposition in VS442 preserved TEB was also higher than those in the VS55
      group since 3days post-rewarm. Both cell viability and osteogenic capability of
      the VS55 group were found to be declined to a negligible level within 15 days
      post-rewarm. Furthermore, it was observed that extending the preservation of TEB
      in VS442 to 3 months did not render any significant effect on its survival and
      osteogenic potential. Thus, the newly developed VS442 vitreous solution was
      demonstrated to be more efficient in maintaining cellular viability and
      osteogenic function for vitreous cryopreservation of TEB over VS55.

PMID- 19576197
TI  - Expression of MafA in pancreatic progenitors is detrimental for pancreatic
      development.
AB  - The transcription factor MafA regulates glucose-responsive expression of insulin.
      MafA-deficient mice have a normal proportion of insulin+ cells at birth but
      develop diabetes gradually with age, suggesting that MafA is required for
      maturation and not specification of pancreatic beta-cells. However, several
      studies show that ectopic expression of MafA may have a role in specification as
      it induces insulin+ cells in chicken gut epithelium, reprograms adult murine
      acinar cells into insulin+ cells in combination with Ngn3 and Pdx1, and triggers
      the lens differentiation. Hence, we examined whether MafA can induce
      specification of beta-cells during pancreatic development. When the MafA
      transgene is expressed in Pdx1+ pancreatic progenitors, both pancreatic mass and
      proliferation of progenitors are reduced, at least partially due to induction of
      cyclin kinase inhibitors p27 and p57. Expression of MafA in Pdx1+ cells until
      E12.5 was sufficient to cause these effects and to disproportionately inhibit the
      formation of endocrine cells in the remnant pancreas. Thus, in mice, MafA
      expression in Pdx1+ pancreatic progenitors is not sufficient to specify insulin+
      cells but in fact deters pancreatic development and the differentiation of
      endocrine cells. These findings imply that MafA should be used to enhance
      maturation, rather than specification, of beta-cells from stem/progenitor cells.

PMID- 19576198
TI  - A role for chemokine signaling in neural crest cell migration and craniofacial
      development.
AB  - Neural crest cells (NCCs) are a unique population of multipotent cells that
      migrate along defined pathways throughout the embryo and give rise to many
      diverse cell types including pigment cells, craniofacial cartilage and the
      peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide
      variety of congenital birth defects including craniofacial abnormalities. The
      chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key
      components in the regulation of cell migration in a variety of tissues. Here we
      describe a novel role for the zebrafish chemokine receptor Cxcr4a in the
      development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a,
      but not Cxcr7b, results in aberrant CNCC migration defects in the neurocranium,
      as well as cranial ganglia dysmorphogenesis. Moreover, overexpression of either
      Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic
      craniofacial cartilages. We propose a model in which Sdf1b signaling from the
      pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important
      for both the proper condensation of the CNCCs into pharyngeal arches and the
      subsequent patterning and morphogenesis of the neural crest derived tissues.

PMID- 19576199
TI  - The Ron receptor tyrosine kinase negatively regulates mammary gland branching
      morphogenesis.
AB  - The Ron receptor tyrosine kinase is expressed in normal breast tissue and is
      overexpressed in approximately 50% of human breast cancers. Despite the recent
      studies on Ron in breast cancer, nothing is known about the importance of this
      protein during breast development. To investigate the functional significance of
      Ron in the normal mammary gland, we compared mammary gland development in wild
      type mice to mice containing a targeted ablation of the tyrosine kinase (TK)
      signaling domain of Ron (TK-/-). Mammary glands from RonTK-/- mice exhibited
      accelerated pubertal development including significantly increased ductal
      extension and branching morphogenesis. While circulating levels of estrogen,
      progesterone, and overall rates of epithelial cell turnover were unchanged,
      significant increases in phosphorylated MAPK, which predominantly localized to
      the epithelium, were associated with increased branching morphogenesis.
      Additionally, purified RonTK-/- epithelial cells cultured ex vivo exhibited
      enhanced branching morphogenesis, which was reduced upon MAPK inhibition.
      Microarray analysis of pubertal RonTK-/- glands revealed 393 genes temporally
      impacted by Ron expression with significant changes observed in signaling
      networks regulating development, morphogenesis, differentiation, cell motility,
      and adhesion. In total, these studies represent the first evidence of a role for
      the Ron receptor tyrosine kinase as a critical negative regulator of mammary
      development.

PMID- 19576200
TI  - Enabled and Capping protein play important roles in shaping cell behavior during
      Drosophila oogenesis.
AB  - During development, cells craft an impressive array of actin-based structures,
      mediating events as diverse as cytokinesis, apical constriction, and cell
      migration. One challenge is to determine how cells regulate actin assembly and
      disassembly to carry out these cell behaviors. During Drosophila oogenesis
      diverse cell behaviors are seen in the soma and germline. We used oogenesis to
      explore developmental roles of two important actin regulators: Enabled/VASP
      proteins and Capping protein. We found that Enabled plays an important role in
      cortical integrity of nurse cells, formation of robust bundled actin filaments in
      late nurse cells that facilitate nurse cell dumping, and migration of somatic
      border cells. During nurse cell dumping, Enabled localizes to barbed ends of the
      nurse cell actin filaments, suggesting its mechanism of action. We further
      pursued this mechanism using mutant Enabled proteins, each affecting one of its
      protein domains. These data suggest critical roles for the EVH2 domain and its
      tetramerization subdomain, while the EVH1 domain appears less critical. Enabled
      appears to be negatively regulated during oogenesis by Abelson kinase. We also
      explored the function of Capping protein. This revealed important roles in oocyte
      determination, nurse cell cortical integrity and nurse cell dumping, and support
      the idea that Capping protein and Enabled act antagonistically during dumping.
      Together these data reveal places that these actin regulators shape oogenesis.

PMID- 19576201
TI  - Rho1 has multiple functions in Drosophila wing planar polarity.
AB  - The frizzled (fz) signaling/signal transduction pathway controls planar cell
      polarity in both vertebrates and invertebrates. Previous data implicated Rho1 as
      a component of the fz pathway in Drosophila but it was unclear how it functioned.
      The existence of a G Protein Binding-Formin Homology 3 (GBD-FH3) domain in
      Multiple Wing Hairs, a downstream component of the pathway suggested that Rho1
      might function by binding to and activating Mwh. We re-examined the role of Rho1
      in wing planar polarity and found that it had multiple functions. Aberrant Rho1
      activity led to changes in the number of hairs formed, changes in cell shape and
      F-actin and changes in cellular junctions. Experiments that utilized Rho effector
      loop mutations argued that these phenotypes were mediated by effects of Rho1 on
      the cytoskeleton and not by effects on transcription. We found strong positive
      genetic interactions between Rho1 and mwh, that Rho1 regulated the accumulation
      of Mwh protein and that these two proteins could be co-immunoprecipitated. The
      Mwh GBD:FH3 domain was sufficient for co-immunoprecipitation with Rho1,
      consistent with this domain mediating the interaction. However, further
      experiments showed that Rho1 function in wing differentiation was not limited to
      interacting with Mwh. We established by genetic experiments that Rho1 could
      influence hair morphogenesis in the absence of mwh and that the disruption of
      Rho1 activity could interfere with the zig zag accumulation pattern of upstream
      fz pathway proteins. Thus, our results argue that in addition to its interaction
      with Mwh Rho1 has functions in wing planar polarity that are parallel to and
      upstream of fz. The upstream function may be an indirect one and associated with
      the requirement for normal apical basal polarity and adherens junctions for the
      accumulation of PCP protein complexes.

PMID- 19576202
TI  - Loss of Tbx2 delays optic vesicle invagination leading to small optic cups.
AB  - Tbx2 is a T-box transcription factor gene that is dynamically expressed in the
      presumptive retina during optic vesicle invagination. Several findings implicate
      Tbx2 in cell cycle regulation, including its overexpression in tumours and
      regulation of proliferation during heart development. We investigated the role of
      Tbx2 in optic cup formation by analysing mice with a targeted homozygous mutation
      in Tbx2. Loss of Tbx2 caused a reduced presumptive retinal volume due to
      increased apoptosis, and a delay in ventral optic vesicle invagination leading to
      the formation of small and abnormally shaped optic cups. Tbx2 is essential for
      maintenance, but not induction of expression of the dorsal retinal determinant,
      Tbx5, and acts downstream of Bmp4, a dorsally expressed gene implicated in human
      microphthalmia. The small retina showed a hypocellular ventral region, loss of
      Fgf15, normally expressed in proliferating central retinal cells, and increased
      numbers of mitotic cells in the dorsal region, indicating that Tbx2 is required
      for normal growth and development across the D-V axis. Dorsal expression of
      potential regulators of retinal growth, Cyp1b1 and Cx43, and the topographic
      guidance molecule ephrinB2, was increased, and intraretinal axons were
      disorganised resulting in a failure of optic nerve formation. Our data provide
      evidence that Tbx2 is required for proper optic cup formation and plays a
      critical early role in regulating regional retinal growth and the acquisition of
      shape during optic vesicle invagination.

PMID- 19576203
TI  - Endocardial cells are a distinct endothelial lineage derived from Flk1+
      multipotent cardiovascular progenitors.
AB  - Identification of multipotent cardiac progenitors has provided important insights
      into the mechanisms of myocardial lineage specification, yet has done little to
      clarify the origin of the endocardium. Despite its essential role in heart
      development, characterization of the endocardial lineage has been limited by the
      lack of specific markers of this early vascular subpopulation. To distinguish
      endocardium from other vasculature, we generated an NFATc1-nuc-LacZ BAC
      transgenic mouse line capable of labeling this specific endothelial subpopulation
      at the earliest stages of cardiac development. To further characterize
      endocardiogenesis, embryonic stem cells (ESCs) derived from NFATc1-nuc-LacZ
      blastocysts were utilized to demonstrate that endocardial differentiation in
      vitro recapitulates the close temporal-spatial relationship observed between
      myocardium and endocardium seen in vivo. Endocardium is specified as a cardiac
      cell lineage, independent from other vascular populations, responding to BMP and
      Wnt signals that enhance cardiomyocyte differentiation. Furthermore, a population
      of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors,
      represents a mesodermal precursor of the endocardial endothelium, as well as
      other cardiovascular lineages. Taken together, these studies emphasize that the
      endocardium is a unique cardiac lineage and provides further evidence that
      endocardium and myocardium are derived from a common precursor.

PMID- 19576204
TI  - Fate of HERS during tooth root development.
AB  - Tooth root development begins after the completion of crown formation in mammals.
      Previous studies have shown that Hertwig's epithelial root sheath (HERS) plays an
      important role in root development, but the fate of HERS has remained unknown. In
      order to investigate the morphological fate and analyze the dynamic movement of
      HERS cells in vivo, we generated K14-Cre;R26R mice. HERS cells are detectable on
      the surface of the root throughout root formation and do not disappear. Most of
      the HERS cells are attached to the surface of the cementum, and others separate
      to become the epithelial rest of Malassez. HERS cells secrete extracellular
      matrix components onto the surface of the dentin before dental follicle cells
      penetrate the HERS network to contact dentin. HERS cells also participate in the
      cementum development and may differentiate into cementocytes. During root
      development, the HERS is not interrupted, and instead the HERS cells continue to
      communicate with each other through the network structure. Furthermore, HERS
      cells interact with cranial neural crest derived mesenchyme to guide root
      development. Taken together, the network of HERS cells is crucial for tooth root
      development.

PMID- 19576206
TI  - Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid
      receptor antagonist, regulates obese-related factors in mice.
AB  - Orally active dual mu-/delta-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH(2)
      Ph (MZ-2) was applied to study body weight gain, fat content, bone mineral
      density, serum insulin, cholesterol and glucose levels in female ob/ob (B6.V
      Lep<ob>/J homozygous) and lean wild mice with or without voluntary exercise on
      wheels for three weeks, and during a two week post-treatment period under the
      same conditions. MZ-2 (10mg/kg/day, p.o.) exhibited the following actions: (1)
      reduced body weight gain in sedentary obese mice that persisted beyond the
      treatment period without effect on lean mice; (2) stimulated voluntary running on
      exercise wheels of both groups of mice; (3) decreased fat content, enhanced bone
      mineral density (BMD), and decreased serum insulin and glucose levels in obese
      mice; and (4) MZ-2 (30 microM) increased BMD in human osteoblast cells (MG-63)
      comparable to naltrexone, while morphine inhibited mineral nodule formation.
      Thus, MZ-2 has potential application in the clinical management of obesity,
      insulin and glucose levels, and the amelioration of osteoporosis.

PMID- 19576205
TI  - Rap1 maintains adhesion between cells to affect Egfr signaling and planar cell
      polarity in Drosophila.
AB  - The small GTPase Rap1 affects cell adhesion and cell motility in numerous
      developmental contexts. Loss of Rap1 in the Drosophila wing epithelium disrupts
      adherens junction localization, causing mutant cells to disperse, and
      dramatically alters epithelial cell shape. While the adhesive consequences of
      Rap1 inactivation have been well described in this system, the effects on cell
      signaling, cell fate specification, and tissue differentiation are not known.
      Here we demonstrate that Egfr-dependent cell types are lost from Rap1 mutant
      tissue as an indirect consequence of DE-cadherin mislocalization. Cells lacking
      Rap1 in the developing wing and eye are capable of responding to an Egfr signal,
      indicating that Rap1 is not required for Egfr/Ras/MAPK signal transduction.
      Instead, Rap1 regulates adhesive contacts necessary for maintenance of Egfr
      signaling between cells, and differentiation of wing veins and photoreceptors.
      Rap1 is also necessary for planar cell polarity in these tissues. Wing hair
      alignment and ommatidial rotation, functional readouts of planar cell polarity in
      the wing and eye respectively, are both affected in Rap1 mutant tissue. Finally,
      we show that Rap1 acts through the effector Canoe to regulate these developmental
      processes.

PMID- 19576207
TI  - Single low-dose administration of pharmacological inhibitor of mitogen-activated
      ERK kinase to the adventitia of the injured rat carotid artery suppresses
      neointima formation and inhibits nuclear ERK signaling.
AB  - Arterial injury has been reported to activate the mitogen-activated ERK kinase
      (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway.
      Pharmacological MEK inhibition was previously shown to inhibit injury-induced
      neointima formation in rodent models, but inhibitor compounds were administered
      either locally at a high dose or systemic treatment was performed over an
      extended period of time. Aim of this study was, therefore, to explore the
      efficiency of single low-dose administration of the MEK inhibitor PD98059 on
      neointima formation in the injured rat carotid artery. The second aim of the
      study was to analyse treatment effects on MEK-dependent signaling and protein
      expression. PD98059 (at doses of 10 and 40 nmol) was administered to the
      adventitia immediately after injury using Pluronic gel as drug carrier. Compared
      to untreated controls, PD98059 treatment (10 nmol) resulted in significant
      reductions of neointima-to-media ratio (by 66%) and injury-induced lumen loss (by
      53%). Conversely, lumen was increased by 33% in PD98059-treated arteries. There
      were no significant differences between the 10 and 40 nmol treatment groups. Dual
      ERK1/2 phosphorylation, and also ERK1/2 protein expression, was significantly
      inhibited by PD98059 treatment. Expression of the transcription factor Ets-1, a
      nuclear target protein of ERK1/2 was significantly suppressed in PD98059-treated
      arteries. Attenuation of neointima formation was associated with significantly
      decreased expression of the proliferation marker PCNA. In contrast, we did not
      find biochemical evidence of increased apoptosis in PD98059-treated arteries. Our
      data show that the single adventitial administration of low-dose MEK inhibitor
      PD98059 is sufficient to suppress neointima formation in injured arteries.

PMID- 19576208
TI  - Molecular cloning and characterization of dog TRPA1 and AITC stimulate the
      gastrointestinal motility through TRPA1 in conscious dogs.
AB  - Transient receptor potential ankyrin1 (TRPA1) is a non-selective cation channel
      activated by cold stimuli under 17 degrees C, mechanosensation, and pungent
      irritants such as allyl isothiocyanates (AITC) and cinnamaldehyde (CA). In this
      study, we cloned the dog orthologue of TRPA1 for the first time and induced its
      heterologous expression in HEK293 cells to investigate its functional properties
      using a fluorescence imaging plate reader-based Ca(2+) influx assay. Moreover, we
      examined the effect of AITC on gastrointestinal motility in dogs. At the amino
      acid level, the sequence of dog TRPA1 was 82-83% identical to that of human,
      mouse, and rat orthologues. TRPA1 is strongly expressed in the brain, cerebellum,
      stomach, pancreas, and small and large intestine of dogs. Like other mammalian
      orthologues, TRPA1 agonists, including AITC, CA, allicin, and diallyl disulfide,
      evoked a concentration-dependent increase in intracellular Ca(2+) influx in dog
      TRPA1-expressing cells. AITC stimulated gastric antrum and jejunum motility and
      induced the occurrence of giant migrating contractions in the colon of fasted
      dogs. The effects of AITC were inhibited by ruthenium red, a TRPA1 antagonist.
      These results indicate that AITC stimulated the gastrointestinal motility through
      TRPA1 in conscious dogs.

PMID- 19576209
TI  - Heart-type fatty acid-binding protein is a useful marker for organ dysfunction
      and leptin alleviates sepsis-induced organ injuries by restraining its tissue
      levels.
AB  - Heart-type fatty acid-binding protein (H-FABP) is widely distributed and has been
      used to diagnose certain diseases. However, its alteration during infection
      evoked organ dysfunction, and the potential association between leptin and it in
      injury or infection has not been investigated. In the current study, serum H
      FABP, leptin, C-reactive protein and interleukin-1beta in the patients with
      pulmonary infection-induced multiple organ dysfunction were detected. Moreover, a
      mouse model of sepsis was established, and serum alanine transaminase, uric acid,
      tissue H-FABP, myeloperoxidase, superoxide dismutase activity and histological
      alterations in lung and intestine were investigated. Serum H-FABP and leptin
      increased simultaneously and significantly in the patients, and leptin alleviated
      pulmonary and intestinal injuries by restraining tissue H-FABP secretions in the
      mouse model of sepsis. Other investigated variables showed different but
      independent alterations. In conclusion, H-FABP represents a useful diagnostic
      marker for organ dysfunction, and its association with leptin will be a novel
      target for emergency aid.

PMID- 19576210
TI  - Toxic peptides in Frazer's fraction interact with the actin cytoskeleton and
      affect the targeting and function of intestinal proteins.
AB  - Celiac disease (CD) is a multisystemic autoimmune inflammation of the intestinal
      tract induced by wheat gluten and related cereals in HLA-DQ2/8 positive
      individuals. An essential role in the pathogenesis of CD is played by a fraction
      of the peptic-tryptic digest of gluten, Frazer's Fraction (FF). Here, we
      investigate the effects of FF on the integrity of intestinal cells with
      particular emphasis on brush border membrane (BBM) components, their subsequent
      trafficking and endocytosis. Caco-2 cells were incubated with FF at different
      concentrations. Thereafter, several protein and lipid components of treated and
      untreated cells were analysed at the molecular, functional and cellular levels.
      The control employed tryptic-peptic digests of ovalbumin. Our results show that
      FF directly interacts with actin in an alternating manner eliciting substantial
      alterations in its integrity and extent in the BBM. These alterations lead to an
      impaired trafficking of SI to the apical membrane and reduction in its enzymatic
      function. ApN and DPPIV follow a transcytotic pathway and are only partly
      affected by FF. By contrast, the trafficking of LPH remains unaffected
      concomitant with its actin-independent trafficking pattern. Finally, the
      endocytic pathway is substantially blocked in FF-treated cells leading to an
      accumulation of cholesterol, and sphingolipids in the BBM. We conclude that FF
      deteriorates the actin cytoskeleton in Caco-2 leading to reduced protein sorting
      and hampered endocytic events with subsequent alterations in the protein and
      lipid composition of the BBM. The reduced levels of the disaccharidase SI in the
      BBM suggest a potential pathomechanism of carbohydrate malabsorption in CD.

PMID- 19576211
TI  - Inhibition of thromboxane synthase induces lung cancer cell death via increasing
      the nuclear p27.
AB  - The role of thromboxane in lung carcinogenesis is not clearly known, though
      thromboxane B2 (TXB(2)) level is increased and antagonists of thromboxane
      receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical
      tumor suppressor, is normally sequestered in the nucleus. The increased nuclear
      p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of
      thromboxane synthase (TXS) induces the death of lung cancer cells and that such
      inhibition is associated with the nuclear p27 level. Our experiment showed that
      the inhibition of TXS significantly induced the death or apoptosis in lung cancer
      cells. The activity of TXS was increased in lung cancer. The nuclear p27 was
      remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell
      death and apoptosis of lung cancer cells, likely via the elevation of the nuclear
      p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of
      p27 by its siRNA recovered the cell death induced by TXS inhibition.
      Collectively, lung cancer cells produce high levels of TXB(2) but their nuclear
      p27 is markedly reduced. The inhibition of TXS results in the p27-related
      induction of cell death in lung cancer cells.

PMID- 19576212
TI  - Stabilization of anaphase midzone microtubules is regulated by Rho during
      cytokinesis in human fibrosarcoma cells.
AB  - The dynamics of astral and midzone microtubules (MTs) must be separately
      regulated during cell division, but the mechanism of selective stabilization of
      midzone MTs is poorly understood. Here we show that, in HT1080 cells, activation
      of Rho is required to stabilize midzone MTs, and to maintain the midzone
      structures after anaphase onset or during cytokinesis. Ect2-depleted cells
      undergoing conventional cytokinesis (cytokinesis A) or contractile ring
      independent cytokinesis (cytokinesis B) formed abnormally thin bundles of midzone
      MTs. C3-loaded mitotic cells with inactivated Rho showed similar but more severe
      disorganization of midzone MTs. In addition, the bundles of astral MTs were
      abnormally abundant along the cell periphery in both Ect2-depleted and C3-loaded
      mitotic cells. Mitotic kinesin-like protein 1 (MKLP1), a component of the spindle
      midzone required for bundling of MTs, was localized only in the narrower
      equatorial regions in Ect2-depleted cells, and disappeared from the midzone
      accompanying the progression of the mitotic phase in C3-loaded cells.
      Stabilization of MTs by taxol was sufficient to maintain the midzone structures
      in C3-loaded mitotic cells. These results, when combined with a preceding
      analysis on another, microtubule-associated Rho GEF (C.J. Bakal, D. Finan, J.
      LaRose, C.D. Wells, G. Gish, S. Kulkarni, P. DeSepulveda, A. Wilde, R. Rottapel,
      The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis, Proc.
      Natl. Acad. Sci. U. S. A. 102 (2005) 9529-9534), suggest that mammalian cells
      have two potential steps that require active Rho for the stabilization of midzone
      MTs during mitosis and cytokinesis.

PMID- 19576213
TI  - Naltrexone and insulin are independently effective but not additive in
      accelerating corneal epithelial healing in type I diabetic rats.
AB  - Patients with diabetes are at increased risk for developing corneal disorders,
      termed diabetic keratopathy. Treatments for diabetic keratopathy are limited.
      Preclinical studies have demonstrated that topical administration of either
      naltrexone (NTX) or insulin (INS) accelerates corneal re-epithelialization in
      type I diabetic rats. This study determined whether the combination of NTX and
      INS would have additive effect(s) on the re-epithelialization of corneal
      abrasions in diabetic male Sprague-Dawley rats beyond either agent alone. Type 1
      diabetes (DB) (glucose levels>400mg/dl) was induced with streptozotocin; glycemic
      levels were not controlled with INS. Eight weeks after induction of diabetes, a
      5mm diameter circular abrasion was created in the center of the cornea in one eye
      of each rat. Eye drops (0.05ml) of INS [1U ( approximately 6nM)] and NTX (10(
      5)M) in Vigamox were administered separately 4 times daily for 7 days (NTX/INS);
      DB control rats received drops of sterile vehicle (DB SV) 4 times daily. Two
      other groups of rats were given only NTX (DB NTX) or only INS (DB INS). Re
      epithelialization was monitored by fluorescein staining, and images were recorded
      with a CCD camera. Areal measurements were made using Optimas software, and the
      percentage of epithelial defect over a 40h period was calculated. Twenty-four
      hour after formation of an abrasion ( approximately 21.7+/-0.4mm(2)area), corneal
      wounds in DB rats treated with NTX, INS, or NTX/INS were significantly smaller
      (p<0.001) than those in DB SV rats, with reductions in the size of the defect
      ranging from 24 to 84%. DB rats treated with NTX or INS alone also were observed
      to have reductions in wound size of 22 and 29%, respectively, from subjects in
      the DB SV group at 16h. At 16h both the DB NTX and DB INS groups had defects that
      were 13 and 27%, respectively, smaller than those for the DB NTX/INS group, and
      at 40h the DB INS animals had 78% smaller corneal wounds than in the DB NTX/INS
      group. Therefore, the DB NTX/INS group exhibited some slight delays in wound
      repair compared to the DB NTX and DB INS groups. Topical application of NTX
      and/or INS to the cornea had no effect on non-invasive measures that included
      ocular morphology, intraocular pressure, or corneal thickness. These data
      demonstrate that although NTX or INS accelerates wound healing, concomitant
      application of NTX and INS to corneal abrasions in diabetic animals does not have
      an additive effect on re-epithelialization.

PMID- 19576214
TI  - Reduction in endothelial tip cell filopodia corresponds to reduced intravitreous
      but not intraretinal vascularization in a model of ROP.
AB  - To determine the effect of a vascular endothelial growth factor receptor 2
      tyrosine kinase (VEGFR2) inhibitor on intravitreous neovascularization (IVNV),
      endothelial tip cell filopodia, and intraretinal vascularization in a rat model
      of retinopathy of prematurity (ROP). Within 4h of birth, newborn Sprague-Dawley
      rat pups and their mothers were cycled between 50% and 10% oxygen daily until
      postnatal day (p)12. Pups were given intravitreous injections of VEGFR2
      inhibitor, SU5416, or control (dimethyl sulfoxide, DMSO) and returned to oxygen
      cycling until p14, then placed into room air. Intravitreous neovascularization
      (IVNV), avascular/total retinal areas, and endothelial tip cell filopodial number
      and length were determined in lectin-labeled neurosensory retinal flat mounts.
      Cryosections or fresh tissue were analyzed for phospho-VEGFR1, phospho-VEGFR2,
      activated caspase-3, or phospho-beta3 integrin. Human umbilical venous (HUVECs)
      and human choroidal endothelial cells (ECs) were treated with VEGFR2 inhibitor to
      determine effect on VEGFR2 phosphorylation and on directed EC migration toward a
      VEGF gradient. Filopodial length and number of migrated ECs were also measured.
      Compared to control, the VEGFR2 inhibitor reduced VEGFR2 phosphorylation in
      HUVECs in vitro and clock hours and areas of IVNV but not percent avascular
      retina in vivo. Filopodial length and number of filopodia/EC tip cell were
      reduced in retinal flat mounts at doses that inhibited IVNV, whereas at lower
      doses, only a reduction in filopodial length/EC tip cell was found. There was no
      difference in phosphorylated beta3 integrin and cleaved caspase-3 labeling in
      VEGFR2 inhibitor-treated compared to control in vivo. Doses of the VEGFR2
      inhibitor that reduced filopodial length and number of filopodia/migrating EC
      corresponded to reduced EC migration in in vitro models. VEGFR2 inhibitor reduced
      IVNV and filopodial number and length/EC tip cell without interfering with
      intraretinal vascularization. Reducing the number and length of
      filopodia/endothelial tip cell may reduce guidance cues for endothelial cells to
      migrate into the vitreous without interfering with migration into the retina
      toward a VEGF gradient.

PMID- 19576215
TI  - Altered microRNA expression following traumatic spinal cord injury.
AB  - MicroRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively
      regulate gene expression at the posttranscriptional level by binding to the 3'
      untranslated region of target mRNAs leading to their translational inhibition or
      sometimes degradation. We uncovered a previously unknown alteration in temporal
      expression of a large set of miRNAs following a contusive spinal cord injury
      (SCI) in adult rats using microarray analysis. These altered miRNAs can be
      classified into 3 categories: (1) up-regulation, (2) down-regulation and (3) an
      early up-regulation at 4 h followed by down-regulation at 1 and 7 days post-SCI.
      The bioinformatics analysis indicates that the potential targets for miRNAs
      altered after SCI include genes encoding components that are involved in the
      inflammation, oxidation, and apoptosis that are known to play important roles in
      the pathogenesis of SCI. These findings suggest that abnormal expression of
      miRNAs may contribute to the pathogenesis of SCI and are potential targets for
      therapeutic interventions following SCI.

PMID- 19576216
TI  - Female androgen patterns and within-pair testosterone compatibility in domestic
      geese (Anser domesticus).
AB  - For successfully raising offspring, long-term monogamous pair partners need to be
      behaviorally and hormonally coordinated. In the monogamous, biparental greylag
      geese (Anser anser) a dyadic pairbond-specific measure, 'within-pair testosterone
      compatibility' (TC) indicated how closely synchronized are seasonal androgen
      levels, which co-varied with reproductive output. Males, in particular, were
      assumed to respond to their females' hormonal and fecundity phases. We now
      present experiments with biparental domestic geese (Anser domesticus) kept as
      pairs to ask whether TC occurs also in these generally polygynous animals. We
      further ask how different conditions of mate choice affect TC and whether
      established TC is maintained during a polygynous flock situation. We measured
      androgen metabolites (AM) non-invasively from individual droppings. In females,
      AM was related with gonadal activity as it increased after GnRH but not ACTH
      challenge. Females with preferred partners had higher maximum AM during egg
      laying and higher rates of initiating incubation than randomly paired females.
      Domestic ganders had seasonal AM patterns typical for polygynous males. Within
      pair TC ranged from almost perfectly positive to non-correlated in domestic geese
      but mate choice did not explain TC variation. TC of previous pairs was generally
      reduced in the flock situation, probably confounded by factors of the social
      environment, i.e. mating opportunity and availability of multiple partners. On
      top of the underlying reproductive physiology our results suggest two episodic
      components of TC: a female androgen responsiveness to the preferred partner at
      least during egg formation, and the male's facultative potential to respond to
      her readiness to breed.

PMID- 19576218
TI  - Treatment with arginine vasotocin alters mating calls and decreases call
      attractiveness in male tungara frogs.
AB  - The peptide hormone arginine vasotocin (AVT) and its mammalian homolog arginine
      vasopressin modulate a variety of social behaviors in vertebrates. In anurans,
      AVT influences the production of advertisement calls, the acoustic signals that
      males use to attract females and repel rival males. In this study, we investigate
      the effects of AVT on call characteristics in the tungara frog (Physalaemus
      pustulosus). Tungara frogs produce a "whine" that is important for species
      recognition; they may also produce a second, attractive call component, the
      "chuck". We used a field playback experiment to determine changes in male calling
      behavior following treatment with AVT. A previous study showed that AVT alters
      call rate and the production of chucks; in the current analysis, we focus on
      changes in the whine. Males produce shorter whines with higher initial
      frequencies following treatment with AVT. Call changes do not vary with a social
      stimulus. We also used female phonotaxis experiments to investigate the effects
      of call changes on female mate choice. Females disfavor the calls produced by
      males treated with exogenous AVT. We suggest that AVT influences motivation to
      call and the motor control of call production, but that over-stimulation of the
      vocal system limited the production of attractive calls in this experimental
      context.

PMID- 19576217
TI  - Fecal endocrine profiles and ejaculate traits in black-footed cats (Felis
      nigripes) and sand cats (Felis margarita).
AB  - Information regarding the reproductive biology of black-footed cats (BFC) and
      sand cats (SC) is extremely limited. Our objectives were to: (1) validate fecal
      hormone analysis (estrogens, E; progestagens, P; androgens, T) for noninvasive
      monitoring of gonadal activity; (2) characterize estrous cyclicity, ovulatory
      mechanisms, gestation, and seasonality; and (3) evaluate male reproductive
      activity via fecal androgen metabolites and ejaculate traits. In both species,
      the estrous cycle averaged 11-12 days. In BFC (n=8), estrus lasted 2.2+/-0.2 days
      with peak concentrations of E (2962.8+/-166.3 ng/g feces) increasing 2.7-fold
      above basal concentrations. In SC (n=6), peak concentrations of E (1669.9+/-83.5
      ng/g feces) during estrus (2.9+/-0.2 days) were 4.0-fold higher than basal
      concentrations. Nonpregnant luteal phases occurred in 26.5% (26 of 98) of BFC
      estrous cycles, but were not observed in SC (0 of 109 cycles). In both species, P
      concentrations during pregnancy were elevated (32.3+/-3.0 microg/g feces BFC;
      8.5+/-0.7 microg/g feces SC) approximately 10-fold above basal concentrations.
      Fecal T concentrations in males averaged 3.1+/-0.1 microg/g feces in BFC and
      2.3+/-0.0 microg/g feces in SC. Following electroejaculation, 200 to 250 microl
      of semen was collected containing 29.9 (BFC) to 36.5 (SC)x10(6) spermatozoa with
      40.4 (SC) to 46.8 (BFC)% normal morphology. All females exhibited estrous cycles
      during the study and spermatozoa were recovered from all males on every
      collection attempt, suggesting poor reproductive success in these species may not
      be due to physiological infertility.

PMID- 19576219
TI  - Differential in vivo response of soft-shell clam hemocytes against two strains of
      Vibrio splendidus: changes in cell structure, numbers and adherence.
AB  - Host-pathogen interaction models in aquatic species are useful tools for
      understanding the pathogenicity of diseases in cultured and wild populations. In
      this study we report the differential in vivo response of soft-shell clam (Mya
      arenaria) hemocytes against two strains of Vibrio splendidus. Responses were
      measured 24h after injecting into the posterior adductor muscle either an endemic
      wild-type strain (7SHRW) or a strain associated with oyster mortalities (LGP32
      GFP). Changes in hemocyte structure (percentage of rounded cells) were assessed
      microscopically. Changes in adherence and hemocyte numbers were analyzed by flow
      cytometric cell counting. Increased percentages of rounded cells were found in
      response to both strains. However, values from the group infected with LGP32-GFP
      were significantly higher (p<0.01) than with 7SHRW. The cell adherence was
      markedly diminished (p<0.001) by LGP32-GFP whereas 7SHRW did not change it
      significantly. Increased numbers of hemocytes (p<0.001) were induced by LGP32
      GFP, while no significant changes were found after infection with 7SHRW. These
      results show the regulatory capacity of soft-shell clams hemocytes to perform
      specific responses against different strains of V. splendidus.

PMID- 19576220
TI  - Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD
      simulations.
AB  - alpha-Synuclein is an intrinsically disordered protein that appears in aggregated
      forms in the brains of patients with Parkinson's disease. The conversion from
      monomer to aggregate is complex, and aggregation rates are sensitive to changes
      in amino acid sequence and environmental conditions. It has previously been
      observed that alpha-synuclein aggregates faster at low pH than at neutral pH.
      Here, we combine NMR spectroscopy and molecular simulations to characterize alpha
      synuclein conformational ensembles at both neutral and low pH in order to
      understand how the altered charge distribution at low pH changes the structural
      properties of these ensembles and leads to an increase in aggregation rate. The N
      terminus, which has a small positive charge at neutral pH due to a balance of
      positively and negatively charged amino acid residues, is very positively charged
      at low pH. Conversely, the acidic C-terminus is highly negatively charged at
      neutral pH and becomes essentially neutral and hydrophobic at low pH. Our NMR
      experiments and replica exchange molecular dynamics simulations indicate that
      there is a significant structural reorganization within the low-pH ensemble
      relative to that at neutral pH in terms of long-range contacts, hydrodynamic
      radius, and the amount of heterogeneity within the conformational ensembles. At
      neutral pH, there is a very heterogeneous ensemble with transient contacts
      between the N-terminus and the non-amyloid beta component (NAC); however, at low
      pH, there is a more homogeneous ensemble that exhibits strong contacts between
      the NAC and the C-terminus. At both pH values, transient contacts between the N-
      and C-termini are observed, the NAC region shows similar exposure to solvent, and
      the entire protein shows similar propensities to secondary structure. Based on
      the comparison of the neutral- and low-pH conformational ensembles, we propose
      that exposure of the NAC region to solvent and the secondary-structure propensity
      are not factors that account for differences in propensity to aggregate in this
      context. Instead, the comparison of the neutral- and low-pH ensembles suggests
      that the change in long-range interactions between the low- and neutral-pH
      ensembles, the compaction of the C-terminal region at low pH, and the uneven
      distribution of charges across the sequence are key to faster aggregation.

PMID- 19576221
TI  - Crystal structure of the HEAT domain from the Pre-mRNA processing factor
      Symplekin.
AB  - The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and
      polyadenylation, although in metazoa the replication-dependent histone mRNAs are
      processed by 3'-end cleavage but not polyadenylation. The macromolecular complex
      responsible for processing both canonical and histone pre-mRNAs contains the
      approximately 1160-residue protein Symplekin. Secondary-structural prediction
      algorithms identified putative HEAT domains in the 300 N-terminal residues of all
      Symplekins of known sequence. The structure and dynamics of this domain were
      investigated to begin elucidating the role Symplekin plays in mRNA maturation.
      The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was
      determined to 2.4 A resolution with single-wavelength anomalous dispersion
      phasing methods. The structure exhibits five canonical HEAT repeats along with an
      extended 31-amino-acid loop (loop 8) between the fourth and fifth repeat that is
      conserved within closely related Symplekin sequences. Molecular dynamics
      simulations of this domain show that the presence of loop 8 dampens correlated
      and anticorrelated motion in the HEAT domain, therefore providing a neutral
      surface for potential protein-protein interactions. HEAT domains are often
      employed for such macromolecular contacts. The Symplekin HEAT region not only
      structurally aligns with several established scaffolding proteins, but also has
      been reported to contact proteins essential for regulating 3'-end processing.
      Together, these data support the conclusion that the Symplekin HEAT domain serves
      as a scaffold for protein-protein interactions essential to the mRNA maturation
      process.

PMID- 19576222
TI  - Histone deacetylases regulate multicellular development in the social amoeba
      Dictyostelium discoideum.
AB  - Epigenetic modifications of histones regulate gene expression and lead to the
      establishment and maintenance of cellular phenotypes during development. Histone
      acetylation depends on a balance between the activities of histone
      acetyltransferases and histone deacetylases (HDACs) and influences
      transcriptional regulation. In this study, we analyse the roles of HDACs during
      growth and development of one of the cellular slime moulds, the social amoeba
      Dictyostelium discoideum. The inhibition of HDAC activity by trichostatin A
      results in histone hyperacetylation and a delay in cell aggregation and
      differentiation. Cyclic AMP oscillations are normal in starved amoebae treated
      with trichostatin A but the expression of a subset of cAMP-regulated genes is
      delayed. Bioinformatic analysis indicates that there are four genes encoding
      putative HDACs in D. discoideum. Using biochemical, genetic and developmental
      approaches, we demonstrate that one of these four genes, hdaB, is dispensable for
      growth and development under laboratory conditions. A knockout of the hdaB gene
      results in a social context-dependent phenotype: hdaB(-) cells develop normally
      but sporulate less efficiently than the wild type in chimeras. We infer that HDAC
      activity is important for regulating the timing of gene expression during the
      development of D. discoideum and for defining aspects of the phenotype that
      mediate social behaviour in genetically heterogeneous groups.

PMID- 19576223
TI  - In a head-on collision, two RNA polymerases approaching one another on the same
      DNA may pass by one another.
AB  - Using a template that contains promoters for T3 and T7 RNA polymerases (RNAPs) in
      opposing orientations, and His-tagged derivatives of these RNAPs that allow
      immobilization on solid matrices, we have determined that a T7 elongation complex
      (EC) may be advanced past a halted T3 EC, and that after the collision the halted
      T3 EC may resume transcription. Since RNAPs moving in opposite directions use two
      different strands of the DNA as their templates, it seems likely that they manage
      to pass by one other by temporarily releasing their nontemplate strand while
      maintaining association with their template strand.

PMID- 19576225
TI  - Deciphering membrane insertion of the diphtheria toxin T domain by specular
      neutron reflectometry and solid-state NMR spectroscopy.
AB  - Insertion and translocation of soluble proteins into and across biological
      membranes are involved in many physiological and pathological processes, but
      remain poorly understood. Here, we describe the pH-dependent membrane insertion
      of the diphtheria toxin T domain in lipid bilayers by specular neutron
      reflectometry and solid-state NMR spectroscopy. We gained unprecedented
      structural resolution using contrast-variation techniques that allow us to
      propose a sequential model of the membrane-insertion process at angstrom
      resolution along the perpendicular axis of the membrane. At pH 6, the native
      tertiary structure of the T domain unfolds, allowing its binding to the membrane.
      The membrane-bound state is characterized by a localization of the C-terminal
      hydrophobic helices within the outer third of the cis fatty acyl-chain region,
      and these helices are oriented predominantly parallel to the plane of the
      membrane. In contrast, the amphiphilic N-terminal helices remain in the buffer,
      above the polar headgroups due to repulsive electrostatic interactions. At pH 4,
      repulsive interactions vanish; the N-terminal helices penetrate the headgroup
      region and are oriented parallel to the plane of the membrane. The C-terminal
      helices penetrate deeper into the bilayer and occupy about two thirds of the acyl
      chain region. These helices do not adopt a transmembrane orientation.
      Interestingly, the T domain induces disorder in the surrounding phospholipids and
      creates a continuum of water molecules spanning the membrane. We propose that
      this local destabilization permeabilizes the lipid bilayer and facilitates the
      translocation of the catalytic domain across the membrane.

PMID- 19576224
TI  - The COP9 signalosome mediates beta-catenin degradation by deneddylation and
      blocks adenomatous polyposis coli destruction via USP15.
AB  - The Wnt/beta-catenin signalling pathway has important roles in normal cellular
      proliferation, development and angiogenesis. Many malignant transformations,
      including sporadic colorectal tumours, are caused by constitutive activation of
      the Wnt route due to mutations in the tumour suppressor protein adenomatous
      polyposis coli (APC) or the beta-catenin oncogene, ultimately resulting in
      reduced beta-catenin degradation by the ubiquitin (Ub) proteasome system (UPS).
      The COP9 signalosome (CSN) regulates the UPS by controlling cullin-RING Ub
      ligases (CRLs). We show here that the CSN and the beta-catenin destruction
      complex cooperate in targeting beta-catenin for degradation by the UPS. Together
      with the CRL that ubiquitinates beta-catenin, they form a supercomplex
      responsible for beta-catenin degradation. Wnt3A, glycogen synthase kinase 3beta
      inhibitors or mutation of CSN-mediated deneddylation induce the disassembly of
      the supercomplex and the accumulation of beta-catenin. Likewise, downregulation
      of the CSN in HeLa cells leads to retarded degradation of beta-catenin.
      Additionally, we found that the knockdown of the CSN causes accelerated
      proteolysis of APC, an essential component of the beta-catenin destruction
      complex, which is degraded by the UPS as beta-catenin. We show here that APC is
      stabilised by the Ub-specific protease 15 (USP15) associated with the CSN. This
      is demonstrated by over-expression of siRNA oligonucleotides against USP15 or by
      over-expression of an USP15 mutant, which is unable to degrade poly-Ub chains.
      Thus, the CSN controls the Wnt/beta-catenin signalling by assisting the assembly
      of beta-catenin-degrading supercomplexes by deneddylation and, simultaneously, by
      stabilising APC via CSN-associated USP15. The CSN regulates the balance between
      beta-catenin and APC. Disturbance of this balance can cause cancer by driving
      cell transformation, tumour angiogenesis and metastasis. A model is provided that
      proposes a role of CSN-mediated deneddylation in the formation of the beta
      catenin-degrading supercomplex and the protection of complex-bound APC via CSN
      associated USP15.

PMID- 19576226
TI  - Vancomycin and oritavancin have different modes of action in Enterococcus
      faecium.
AB  - The increasing frequency of Enterococcus faecium isolates with multidrug
      resistance is a serious clinical problem given the severely limited number of
      therapeutic options available to treat these infections. Oritavancin is a
      promising new alternative in clinical development that has potent antimicrobial
      activity against both staphylococcal and enterococcal vancomycin-resistant
      pathogens. Using solid-state NMR to detect changes in the cell-wall structure and
      peptidoglycan precursors of whole cells after antibiotic-induced stress, we
      report that vancomycin and oritavancin have different modes of action in E.
      faecium. Our results show the accumulation of peptidoglycan precursors after
      vancomycin treatment, consistent with transglycosylase inhibition, but no
      measurable difference in cross-linking. In contrast, after oritavancin exposure,
      we did not observe the accumulation of peptidoglycan precursors. Instead, the
      number of cross-links is significantly reduced, showing that oritavancin
      primarily inhibits transpeptidation. We propose that the activity of oritavancin
      is the result of a secondary binding interaction with the E. faecium
      peptidoglycan. The hypothesis is supported by results from (13)C{(19)F}
      rotational-echo double-resonance (REDOR) experiments on whole cells enriched with
      l-[1-(13)C]lysine and complexed with desleucyl [(19)F]oritavancin. These
      experiments establish that an oritavancin derivative with a damaged d-Ala-d-Ala
      binding pocket still binds to E. faecium peptidoglycan. The (13)C{(19)F} REDOR
      dephasing maximum indicates that the secondary binding site of oritavancin is
      specific to nascent and template peptidoglycan. We conclude that the inhibition
      of transpeptidation by oritavancin in E. faecium is the result of the large
      number of secondary binding sites relative to the number of primary binding
      sites.

PMID- 19576227
TI  - Segmented transition pathway of the signaling protein nitrogen regulatory protein
      C.
AB  - Recent advances in experimental methods provide increasing evidence that proteins
      sample the conformational substates that are important for function in the
      absence of their ligands. An example is the receiver domain of nitrogen
      regulatory protein C, a member of the phosphorylation-mediated signaling family
      of "two-component systems." The receiver domain of nitrogen regulatory protein C
      samples both inactive conformation and the active conformation before
      phosphorylation. Here we determine a possible pathway of interconversion between
      the active state and the inactive state by targeted molecular dynamics
      simulations and quasi-harmonic analysis; these methods are used because the
      experimental conversion rate is in the high microsecond range, longer than those
      that are easily accessible to atomistic molecular dynamics simulations. The
      calculated pathway is found to be composed of four consecutive stages described
      by different progress variables. The lowest quasi-harmonic principal components
      from unbiased molecular dynamics simulations on the active state correspond to
      the first stage, but not to the subsequent stages of the transition. The targeted
      molecular dynamics pathway suggests that several transient nonnative hydrogen
      bonds may facilitate the transition.

PMID- 19576229
TI  - Equilibrium mechanics of monolayered epithelium.
AB  - In order to fully understand the epithelial mechanics it is essential to
      integrate different levels of epithelial organization. In this work, we propose a
      theoretical approach for connecting the macroscopic mechanical properties of a
      monolayered epithelium to the mechanical properties at the cellular level. The
      analysis is based on the established mechanical models-at the macroscopic scale
      the epithelium is described within the mechanics of thin layers, while the
      cellular level is modeled in terms of the cellular surface (cortical) tension and
      the intercellular adhesion. The macroscopic elastic energy of the epithelium is
      linked to the energy of an average epithelial cell. The epithelial equilibrium
      state is determined by energy minimization and the macroscopic elastic moduli are
      calculated from deformations around the equilibrium. The results indicate that
      the epithelial equilibrium state is defined by the ratio between the adhesion
      strength and the cellular surface tension. The lower and the upper bounds for
      this ratio are estimated. If the ratio is small, the epithelium is cuboidal, if
      it is large, the epithelium becomes columnar. Importantly, it is found that the
      cellular cortical tension and the intercellular adhesion alone cannot produce the
      flattened squamous epithelium. Any difference in the surface tension between the
      apical and basal cellular sides bends the epithelium towards the side with the
      larger surface tension. Interestingly, the analysis shows that the epithelial
      area expansivity modulus and the shear modulus depend only on the cellular
      surface tension and not on the intercellular adhesion. The results are presented
      in a general analytical form, and are thus applicable to a variety of monolayered
      epithelia, without relying on the specifics of numerical finite-element methods.
      In addition, by using the standard theoretical tools for multi-laminar systems,
      the results can be applied to epithelia consisting of layers with different
      mechanical properties.

PMID- 19576228
TI  - Functional importance of bacteriophage phi29 DNA polymerase residue Tyr148 in
      primer-terminus stabilisation at the 3'-5' exonuclease active site.
AB  - Recent crystallographic resolution of varphi29 DNA polymerase complexes with
      ssDNA at its 3'-5' exonuclease active site has allowed the identification of
      residues Pro129 and Tyr148 as putative ssDNA ligands, the latter being conserved
      in the Kx(2)h motif of proofreading family B DNA polymerases. Single substitution
      of varphi29 DNA polymerase residue Tyr148 to Ala rendered an enzyme with a
      reduced capacity to stabilize the binding of the primer terminus at the 3'-5'
      exonuclease active site, not having a direct role in the catalysis of the
      reaction. Analysis of the 3'-5' exonuclease on primer/template structures showed
      a critical role for residue Tyr148 in the proofreading of DNA polymerisation
      errors. In addition, Tyr148 is not involved in coupling polymerisation to strand
      displacement in contrast to the catalytic residues responsible for the
      exonuclease reaction, its role being restricted to stabilisation of the frayed 3'
      terminus at the exonuclease active site. Altogether, the results lead us to
      extend the consensus sequence of the above motif of proofreading family B DNA
      polymerases into Kx(2)hxA. The different solutions adopted by proofreading DNA
      polymerases to stack the 3' terminus at the exonuclease site are discussed. In
      addition, the results obtained with mutants at varphi29 DNA polymerase residue
      Pro129 allow us to rule out a functional role as ssDNA ligand for this residue.

PMID- 19576230
TI  - Targeting peroxynitrite driven nitroxidative stress with synzymes: A novel
      therapeutic approach in chronic pain management.
AB  - Morphine sulfate and other opiate/narcotic analgesics are the most effective
      treatments for acute and chronic severe pain. However, their clinical utility is
      often hampered by the development of analgesic tolerance. This complex
      pathophysiological cycle contributes significantly to decreased quality of life
      in the growing population of subjects with chronic pain due to oversedation,
      reduced physical activity, respiratory depression, constipation, potential for
      addiction, and other side-effects. Accordingly, there is growing interest in new
      approaches that would maintain opiate efficacy during repetitive dosing without
      engendering tolerance or unacceptable side-effects. Considerable evidence
      implicates nitroxidative stress in the development of pain of several etiologies
      and importantly in opiate antinociceptive tolerance, caused by the presence of
      superoxide, O(2)(-), (SO) nitric oxide, NO (NO) and more recently peroxynitrite,
      ONOO(-) or its conjugate acid ONOOH, (PN) that is the product of their
      interaction. To this end, several antioxidant synthetic enzymes (synzymes) have
      been developed to effectively prevent the formation of PN (superoxide dismutase
      mimetics, SODms) or to decompose PN once it is formed (PN decomposition
      catalysts). The objectives of this mini-review written on PN and morphine
      antinociceptive tolerance are to 1) summarize recent advances made in the
      development of novel synzymes as therapeutics, 2) discuss the importance of
      nitroxidative stress in opiate anatinociceptive tolerance and 3) argue that PN is
      a rational target for therapeutic intervention in pain management. These concepts
      provide a pharmacological basis for developing inhibitors of PN biosynthesis as
      novel non-narcotic analgesics, thus addressing a large and currently unmet
      medical need with major socioeconomic consequences.

PMID- 19576232
TI  - Genetic pathways to colorectal cancer.
AB  - The colorectal cancer paradigm explains how genetic and histological changes lead
      normal epithelial cell to transform into pre-malignant adenomas then progress to
      malignant carcinomas. Using the Genetic Alterations in Cancer Knowledge System
      intragenic allele loss and gene mutation data from approximately 9000 colorectal
      tumors were compared to the model of colorectal tumor development. The
      distribution of mutations along the TP53 codons as a function of tumorigenesis
      also was analyzed. Alterations of APC, KRAS and TP53 were observed in a higher
      percentage of adenocarcinomas compared to adenomas (P<0.05) indicating that the
      alterations accumulated with malignancy. Alterations in BRAF, CTNNB, HRAS and
      NRAS were infrequent regardless of morphology. Differences were observed in the
      distribution of TP53 mutations with tumorigenesis. Mutations (single base
      substitutions) occurred most frequently at codons 175 and 273 in both tumor
      types; however, in adenocarcinomas the mutation incidence at codon 248 was
      approximately three times that reported in adenomas. It is proposed that the
      higher incidence of mutation at codon 248 is a later event in colorectal
      tumorigenesis that occurs as the tumors become malignant.

PMID- 19576231
TI  - Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive
      action of the cannabinoid receptor agonist anandamide.
AB  - AIMS: In this study, we investigated whether the opioid system and the nitric
      oxide pathway were involved in the peripheral antinociception induced by a
      cannabinoid receptor agonist anandamide. MAIN METHODS: Hyperalgesia was induced
      by a subcutaneous injection of carrageenan (250 microg) into the plantar surface
      of the rat's hindpaw and measured by the paw pressure test 3h after injection.
      The weight in grams (g) required to elicit a nociceptive response, paw flexion,
      was determined as the nociceptive threshold. KEY FINDINGS: Anandamide elicited a
      dose-dependent (50, 75, and 100 ng per paw) antinociceptive effect. The highest
      dose of anandamide did not produce antihyperalgesia in the contralateral paw,
      indicating a peripheral site of action. The CB(1) receptor antagonist AM251 (20,
      40, 80 and 160mug per paw) antagonized peripheral antihyperalgesia induced by
      anandamide (100 ng), in a dose-dependent manner, suggesting CB(1) receptor
      activation. Anandamide-induced peripheral antihyperalgesia was reverted by
      blockers of the l-arginine/NO/cGMP pathway N(G)-nitro-l-arginine (NOARG; 24, 36
      and 48 microg per paw) and 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25,
      50 and 100 microg per paw), in a dose-dependent manner. Furthermore, opioid
      receptor antagonist naloxone (12.5, 25 and 50 microg per paw) antagonized the
      peripheral antihyperalgesia induced by anandamide. SIGNIFICANCE: This study
      provides evidence that the peripheral antinociceptive effect of the cannabinoid
      receptor agonist anandamide may result from l-arginine/NO/cGMP pathway activation
      and that the opioid system is also involved.

PMID- 19576233
TI  - DNA double-strand breaks: their production, recognition, and repair in
      eukaryotes.
AB  - Human cells accumulate at least 10,000 DNA lesions every day. Failure to repair
      such lesions can lead to mutations, genomic instability, or cell death. Among the
      various types of damage which can be expressed in a cell, DNA double-strand
      breaks (DSBs) represent the most serious threat. Different kinds of physical,
      chemical, and biological factors have been reported to induce DNA lesions,
      including DSBs. The aim of this review is to provide a basic understanding and
      overview of how DSBs are produced, recognized and repaired, and to describe the
      role of some of the genes and proteins involved in DSB repair.

PMID- 19576234
TI  - Anxiety and spatial attention moderate the electrocortical response to aversive
      pictures.
AB  - Aversive stimuli capture attention and elicit increased neural activity, as
      indexed by behavioral, electrocortical and hemodynamic measures; moreover,
      individual differences in anxiety relate to a further increased sensitivity to
      threatening stimuli. Evidence has been mixed, however, as to whether aversive
      pictures elicit increased neural response when presented in unattended spatial
      locations. In the current study, ERP and behavioral data were recorded from 49
      participants as aversive and neutral pictures were simultaneously presented in
      spatially attended and unattended locations; on each trial, participants made
      same/different judgments about pictures presented in attended locations. Aversive
      images presented in unattended locations resulted in increased error rate and
      reaction time. The late positive potential (LPP) component of the ERP was only
      larger when aversive images were presented in attended locations, and this
      increase was positively correlated with self-reported state anxiety. Findings are
      discussed in regard to the sensitivity of ERP and behavioral responses to
      aversive distracters, and in terms of increased neural processing of threatening
      stimuli in anxiety.

PMID- 19576235
TI  - Voice perception in blind persons: a functional magnetic resonance imaging study.
AB  - Early blind persons have often been shown to be superior to sighted ones across a
      wide range of non-visual perceptual abilities, which in turn are often explained
      by the functionally relevant recruitment of occipital areas. While voice stimuli
      are known to involve voice-selective areas of the superior temporal sulcus (STS)
      in sighted persons, it remains unknown if the processing of vocal stimuli
      involves similar brain regions in blind persons, or whether it benefits from
      cross-modal processing. To address these questions, we used fMRI to measure
      cerebral responses to voice and non-voice stimuli in blind (congenital and
      acquired) and sighted subjects. The global comparison of all sounds vs. silence
      showed a different pattern of activation between blind (pooled congenital and
      acquired) and sighted groups, with blind subjects showing stronger activation of
      occipital areas but weaker activation of temporal areas centered around Heschl's
      gyrus. In contrast, the specific comparison of vocal vs. non-vocal sounds did not
      isolate activations in the occipital areas in either of the blind groups. In the
      congenitally blind group, however, it led to a stronger activation in the left
      STS, and to a lesser extent in the fusiform cortex, compared to both sighted
      participants and those with acquired blindness. Moreover, STS activity in
      congenital blind participants significantly correlated with performance in a
      voice discrimination task. This increased recruitment of STS areas in the blind
      for voice processing is in marked contrast with the usual cross-modal recruitment
      of occipital cortex.

PMID- 19576236
TI  - Costs of pair-bonding and paternal care in male prairie voles (Microtus
      ochrogaster).
AB  - The direct costs of paternal care are relatively well documented in primates,
      however little research has explored these effects in monogamous rodents. The
      present study examines the long-term effects that pairing and parenting have on
      male prairie voles. We hypothesized that there would be a significant weight loss
      over the course of pairing and parenting, presumably from the energetic demands
      that accompany these changes in social condition. In a longitudinal study, we
      followed ten male prairie voles through being housed with their brother; paired
      with a female; and caring for three consecutive litters. We found a significant
      drop in bodyweight across time, with maximum weight loss near the weaning of the
      first litter. At that same time, feeding increased, leading to possible recovery
      in weight; however, leptin levels dropped precipitously across time and did not
      recover. Corticosterone did not change significantly across time points, and
      overall activity levels also did not vary significantly over the course of the
      study. In addition, newly paired males showed a significant increase in
      preference for a 2% sucrose solution during a three-hour test, indicating a
      metabolic need for more calories. A cross-sectional study confirmed leptin and
      corticosterone findings, and showed significant loss of subcutaneous (inguinal)
      fat in males that had cared for a litter of pups, when compared to males housed
      with their brothers or newly paired males. These results suggest that
      cohabitation with a female, and caring for pups, all have costs for male prairie
      voles.

PMID- 19576237
TI  - Sensitivity to spatial frequency and orientation content is not specific to face
      perception.
AB  - Prior work using a matching task between images that were complementary in
      spatial frequency and orientation information suggested that the representation
      of faces, but not objects, retains low-level spatial frequency (SF) information
      [Biederman, I., & Kalocsai, P. (1997). Neurocomputational bases of object and
      face recognition. Philosophical Transactions of the Royal Society of London,
      Series B Biological Sciences, 352, 1203-1219]. In two experiments, we reexamine
      the claim that face perception is uniquely sensitive to changes in SF. In
      contrast to prior work, we used a design allowing the computation of sensitivity
      and response criterion for each category, and in one experiment, equalized low
      level image properties across object categories. In both experiments, we find
      that observers are sensitive to SF and orientation changes for upright and
      inverted faces and non-face objects. Differential response biases across
      categories contributed to a larger sensitivity for faces, but even sensitivity
      showed a larger effect for faces, especially when faces were upright and in a
      front-facing view. However, when objects were inverted, or upright but shown in a
      three-quarter view, the matching of objects and faces was equally sensitive to SF
      changes. Accordingly, face perception does not appear to be uniquely affected by
      changes in spatial filter components.

PMID- 19576239
TI  - Expression of Hsp90 chaperone [corrected] proteins in human tumor tissue.
AB  - The activity of many oncogenic proteins depends on the molecular chaperone Hsp90.
      Recent studies indicate that tumorigenesis is associated with increased
      expression of chaperones, such as Hsp90. However, little is known about the
      isoform dependence and cochaperone contribution on tumor formation. Here we
      report the first systematic expression profiling for Hsp90alpha and Hsp90beta,
      the cochaperones Aha1, Cdc37, p23, Tpr2, and the Hsp90 dependent transcription
      factor HSF1 in a set of different tumor tissue samples. We find that in 10 out of
      17 human tumors the expression level of at least one Hsp90 or Hsp90 cochaperone
      protein is significantly elevated. However, individual tumors show unique
      patterns of expression. Furthermore, Hsp90alpha and Hsp90beta expression levels
      are not related. Our results suggest that expression profiling of Hsp90alpha and
      Hsp90beta and its cochaperone proteins may be useful for cancer diagnosis and
      prognosis as well as for tailoring of drugs that interfere with the Hsp90 system
      in a tumor specific manner.

PMID- 19576238
TI  - Infusions of bicuculline to the ventral tegmental area attenuates sexual,
      exploratory, and anti-anxiety behavior of proestrous rats.
AB  - Actions of 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), in the midbrain
      ventral tegmental area (VTA) modulate sexual receptivity of female rats. Actions
      of 3alpha,5alpha-THP at GABAergic substrates in the VTA are known to modulate
      consummatory aspects of sexual behavior among rodents, such as lordosis. However,
      the extent to which GABA(A) receptors in the VTA are important for appetitive
      (exploratory, anti-anxiety, social) aspects of sexual receptivity is not well
      understood. Proestrous rats were bilaterally-infused with saline or bicuculline
      (100 ng), a GABA(A) receptor antagonist, to the VTA or missed control sites. Rats
      were assessed for exploratory/anti-anxiety (open field/elevated plus maze),
      social (social interaction), and sexual (paced-mating) behavior. Compared to
      saline or missed site controls, intra-VTA bicuculline significantly reduced the
      number of central entries in an open field, time spent on the open arms of an
      elevated plus maze, frequency and intensity of lordosis, anti-aggression towards
      a male, pacing of sexual contacts, and 3alpha,5alpha-THP concentrations in
      midbrain and hippocampus. Bicuculline-infused rats also displayed less
      affiliation with a novel conspecific, fewer sexual solicitations, and had lower
      3alpha,5alpha-THP concentrations in diencephalon and cortex, albeit these were
      not significant differences. Thus, actions at GABA(A) receptors in the midbrain
      VTA are essential for appetitive and consummatory aspects of sexual receptivity
      among rats.

PMID- 19576240
TI  - Atlantic salmon IPS-1 mediates induction of IFNa1 and activation of NF-kappaB and
      localizes to mitochondria.
AB  - The striking difference in evolution of type I IFN genes of fish and mammals
      poses the question of whether these genes are induced through similar or
      different signalling pathways in the two vertebrate groups. Previous work has
      shown that expression of both Atlantic salmon (Salmo salar) IFNa1 and mammalian
      IFN-beta genes is dependent on IRF and NF-kappaB elements in their promoters. In
      mammals, IFN-beta transcription is induced through the RIG-I/MDA5 pathway where
      the adaptor protein IPS-1 plays a key role in the signal transduction. In this
      work we show that an Atlantic salmon homologue of IPS-1 (AsIPS-1) mediates
      activation of the salmon IFNa1 promoter and an NF-kappaB driven promoter. AsIPS-1
      shares only 18% identity in amino acid sequence with human IPS-1, but possesses
      the CARD, proline-rich and transmembrane domains found in mammalian IPS-1.
      Overexpression of AsIPS-1 resulted in induction of an antiviral state in the
      cells apparently due to induction of IFN. Deletion of the CARD and transmembrane
      domains of AsIPS-1 abolished its ability to activate the IFNa1 promoter and the
      NF-kappaB driven promoter, and thus its ability to induce an antiviral state.
      AsIPS-1 is located to mitochondria similar to human IPS-1. Taken together, IPS-1
      plays a key role in the induction of Atlantic salmon IFNa1, which appears to be
      the first and major IFN induced in host cells upon recognition of viral dsRNA.

PMID- 19576241
TI  - Thirteen-year follow-up of patients with tri-ortho-cresyl phosphate poisoning in
      northern suburbs of Xi'an in China.
AB  - Based on reports published so far, organophosphorus (OP) compounds do remarkable
      harm to human health. In 1995 there was an outbreak of organophosphorus-ester
      induced delayed neuropathy (OPIDN) due to tri-ortho-cresyl phosphate (TOCP)
      poisoning in northern suburbs of Xi'an in China. The 74 affected patients were
      treated and followed up after definite diagnosis. 13 years later, all the
      epidemiological data obtained from 61 survivors were evaluated, and 15 patients
      underwent clinical, laboratory, neuroimaging and electrophysiological
      examinations. In addition, a review of the literature about the possible
      mechanism of OPIDN was made. According to our investigation, of 61 survivors, 35
      patients almost regained normal function of limbs and work outside; 23 patients
      walked with bilateral support and could perform housework; and 3 patients could
      not self-care. The patients undergoing examinations presented spasticity and
      minor lower leg muscle atrophy without sensory impairment. Laboratory
      investigations and brain and spinal cord magnetic resonance imaging examinations
      were normal. Neurophysiological investigations also showed normal
      electroencephalogram and visual, brainstem auditory and somatosensory evoked
      potentials. Motor evoked potential (MEP) obtained from the upper limbs had normal
      central motor conduction time (CMCT). However, the CMCT of MEP response recorded
      from the bilateral lower limbs was delayed, or showed even no MEP responses.
      Motor and sensory nerve conduction velocity and electromyography studies were
      normal except for two severely affected patients. TOCP showed long-term effects
      on the nervous system and influenced the quality of life. OP compounds should be
      strictly regulated to prevent similar occurrences.

PMID- 19576243
TI  - Changes in neurotransmitter receptor expression levels in rat brain after 4-week
      exposure to 1-bromopropane.
AB  - 1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, exhibits
      neurotoxicity and reproductive toxicity in animals and humans. The present study
      investigated the effects of exposure to 1-BP on expression of neurotransmitter
      receptor genes in the rat brain to explore possible biomarkers for central
      neurotoxicity and find brain regions sensitive for microarray analysis. Thirty
      six F344 rats were divided at random into four equal groups of nine and exposed
      to 1-BP at 0, 400, 800 and 1000 ppm for 8 h/day; 7 days/week for 4 weeks. Total
      RNA from different brain regions was extracted and real-time PCR was conducted to
      quantify the mRNA levels of serotonin, dopamine and GABA receptors. Western blot
      analysis for specific regions of interest was also carried out to determine the
      protein levels. The mRNAs of 5HTr2a, D2R and GABAa1 were down regulated in a 1-BP
      dose-dependent manner in the hippocampus. The mRNA levels of 5HTr1a, 5HTr2a, D1R
      and GABAa1 were significantly decreased in the cortex of rats exposed to 800 ppm,
      but not to 1000 ppm. The mRNAs of 5HTr1a and 5HTr3a in the pons-medulla were
      decreased in rats exposed to 400 ppm or higher concentrations. The mRNA
      expression of D2R in the hippocampus and 5HTr1a and 5HTr3a in the pons-medulla
      oblongata were the most sensitive indicators of 1-BP neurotoxicity. The results
      suggest that mRNA expression analysis is useful in identifying brain regions
      susceptible to 1-BP, as well as providing potential biomarkers for central
      nervous system toxicity.

PMID- 19576242
TI  - The relation of lead neurotoxicity to the event-related potential P3b component
      in Inuit children from arctic Quebec.
AB  - The event-related potential (ERP) P3b, a cognitive electrophysiological measure
      that has been linked to working memory processing in many experimental paradigms,
      was measured in Inuit children from Nunavik (Arctic Quebec, Canada) to assess
      lead (Pb) neurotoxicity. Visual and auditory oddball paradigms were administered
      at 5 (N=27) and 11 (N=110) years of age, respectively, to elicit this ERP
      component. Pearson correlations and multiple regression analyses were performed
      to examine the associations between Pb levels and P3b parameters (peak latency
      and amplitude). Greater prenatal Pb exposure was related to a decrease in P3b
      amplitude at 5 years of age, and early childhood Pb exposure was associated with
      delayed P3b latency at 5 years. No significant association was observed at 11
      years. These results, in line with those from previous neurobehavioral studies,
      suggest that Pb exposure affects cognitive processing in children even though the
      Pb levels measured in a large majority of our sample were below the threshold
      value for public health intervention used by federal agencies. This study
      strengthens the arguments for reducing sources of Pb exposure in Nunavik and for
      lowering the blood Pb concentrations considered "acceptable" in governmental
      policies.

PMID- 19576245
TI  - WITHDRAWN: Anti-relapse medications: Preclinical models for drug addiction
      treatment.
AB  - This article has been withdrawn at the request of the authors. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 19576244
TI  - Mechanisms underlying the developmental neurotoxic effect of PBDE-47 and the
      enhanced toxicity associated with its combination with PCB153 in rats.
AB  - To explore the mechanisms underlying the developmental neurotoxic effect of PBDE
      47 and its interaction with PCB153, expression levels of mRNA and proteins of the
      x-chromosome-linked inhibitor of apoptosis protein (XIAP), death associated
      protein kinase (DAPK), caspase3, caspase12 and cytochrome C in the hippocampus of
      2-month-old rats exposed to a single oral dose of PBDE-47 and/or PCB153 on post
      natal day (PND) 10 were examined. Four levels of PBDE-47 (0, 1, 5, 10 mg/kg) and
      two levels of PCB153 (0 and 5mg/kg) were added to corn oil in a 4 x 2 factorial
      completely randomized design study. Meanwhile, the ultrastructures of neurons in
      the hippocampal CA1 region were observed and the learning and memory capacities
      were measured in these rats. The results suggested that the mRNA and protein
      expression levels of all examined genes (with the exception of cytochrome C mRNA
      in female rats) were significantly changed at some doses (P<0.05); additionally,
      the total distance swam by rats to reach an escape platform was significantly
      increased and the ratio of distance taken in the platform quadrant to total
      distance was notably decreased in all treated groups in the water maze experiment
      (P<0.05) compared to the control. Numerous alterations were observed in the
      ultrastructure of neurons in PBDE-47 alone or combination of PBDE-47 and PCB153
      groups. Furthermore, an interaction was found between PBDE-47 and PCB153 in
      lengthening the total distance taken to the platform and decreasing the platform
      quadrant ratios in the water maze experiment, as well as in the inducing of
      caspase3, caspase12 and cytochrome C mRNA and protein expression (with exception
      of cytochrome C mRNA in female rats) in the hippocampus. We conclude that PBDE-47
      may induce developmental neurotoxicity in rats via three classic apoptosis
      pathways, and it may interact with PCB153 to enhance developmental neurotoxicity.

PMID- 19576246
TI  - Lipids as targets for novel anti-inflammatory therapies.
AB  - Lipids serve important functions as membrane constituents and also as energy
      storing molecules. Besides these functions certain lipid species have now been
      recognized as signalling molecules that regulate a multitude of cellular
      responses including cell growth and death, and also inflammatory reactions.
      Bioactive lipids are generated by hydrolysis from membrane lipids mainly by
      phospholipases giving rise to fatty acids and lysophospholipids that either
      directly exert their function or are further converted to active mediators. This
      review will summarize the present knowledge about bioactive lipids that either
      promote or attenuate inflammatory reactions. These lipids include polyunsaturated
      fatty acids (PUFA), eicosanoids including the epoxyeicosatrienoic acids (EET),
      peroxisome proliferation activating receptor (PPAR) activators, cannabinoids and
      the sphingolipids ceramide, sphingosine 1-phosphate and
      sphingosylphosphorylcholine.

PMID- 19576247
TI  - A novel method for subarachnoid hemorrhage to induce vasospasm in mice.
AB  - Mouse models take advantage of genetic manipulations that can be achieved in this
      species. There are currently two accepted mouse models of subarachnoid hemorrhage
      (SAH) and cerebral vasospasm (CVs). Both are technically demanding and labor
      intensive. In this study, we report a reproducible and technically feasible
      method to induce SAH, and subsequently CVs, in mice. We tested this model in
      multiple strains of mice that are commonly used for genetic manipulation.
      METHODS: SAH was induced in C57BL/6NCr, FVB, 129S1, BalbC and SJL mice, weighing
      28-32 g, by an intracisternal vessel transection technique. Animals were perfused
      with India ink at 24h postprocedure and vessel diameters were quantified. Brain
      slices were obtained for hematoxylin-eosin staining (H&E) to look for vascular
      changes consistent with CVs. RESULTS: There was no mortality during or after the
      procedure. Four of the five mouse strains showed significant CVs at 24 h
      postprocedure characterized by decreased vessel diameter of the middle cerebral
      artery close to the Circle of Willis. Histologically, the vessel wall displayed
      significant corrugation and thickening, consistent with CVs. CONCLUSION: A novel
      mouse model to induce SAH is described and tested in several mouse strains. Four
      of the five strains used in this study developed CVs after the induction of SAH.
      The procedure is brief, straightforward, reproducible with low mortality, and
      applicable to commonly used background strains for genetically engineered mice.

PMID- 19576249
TI  - Effective inhibition of hepatitis E virus replication in A549 cells and piglets
      by RNA interference (RNAi) targeting RNA-dependent RNA polymerase.
AB  - RNA interference (RNAi) is a natural mechanism for suppressing or silencing
      expression of aberrant or foreign genes. It is a powerful antiviral strategy that
      has been widely employed to protect hosts from viral infection. Hepatitis E (HE)
      is an acute fulminant hepatitis in adults that has particularly high mortality in
      pregnant women. At this point in time, there is no vaccine or antiviral treatment
      that is effective against the infectious agent, HEV. The nonstructural
      polyprotein region possesses an RNA-dependent RNA polymerase (RdRp) that is
      responsible for the replication of the viral RNA genome. RdRp is therefore
      regarded as one of the most attractive candidates for RNA interference (RNAi). In
      the present study, the high efficiency and specificity of siRNA were evaluated by
      Real-Time quantitative PCR and Western blot assays. Protective effects against
      HEV infection were achieved in A549 cells and in piglets. In piglets treated with
      a shRNA-RdRp-1 expression plasmid prior to HEV inoculation, HEV antigens were
      significantly reduced in the liver, spleen, and kidneys, and the activities of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total
      bilirubin (TBIL) were clearly decreased. These results suggested that RNAi is a
      potentially effective antiviral strategy against HEV replication and infection.

PMID- 19576248
TI  - Virucidal activity of polysaccharide extracts from four algal species against
      herpes simplex virus.
AB  - Herpes simplex virus types 1 and 2 (HSV-1, HSV-2) infections are common, but can
      cause serious infections in neonates and the immunocompromised. Drugs currently
      used to treat cutaneous or genital HSV infections are effective in limiting
      disease, but the emergence of drug resistant viruses in immunocompromised
      individuals can be problematic. While the prophylactic oral treatment with
      antiviral drugs can reduce virus shedding and transmission, there is a need for
      topical microbicides that have the potential to limit sexual transmission of the
      virus. Previous reports demonstrated the antiviral activity of complex sulfated
      polysaccharides extracted from various species of marine algae and suggested that
      they interfered with the attachment of virions to host cells. Here, we evaluated
      the antiviral activity of extracts from Undaria pinnatifida, Splachnidium
      rugosum, Gigartina atropurpurea, and Plocamium cartilagineum against HSV-1 and
      HSV-2. These extracts exhibited good activity when added during the first hour of
      viral infection, but were ineffective if added later. Plaque reduction assays,
      when the extracts were added prior to viral inoculation, yielded EC(50) values
      that ranged from 2.5-3.6 microg/ml for HSV-1 and 0.7-6.6 microg/ml for HSV-2.
      None of the extracts exhibited significant toxicity in a neutral red uptake assay
      (IC(50) >100 microg/ml). Subsequent assays showed that the compounds had potent
      virucidal activity and were active at very low concentrations. We conclude that
      these extracts are nontoxic and effective virucidal agents that warrant further
      investigation to examine their potential role in the prevention of HSV infections
      of humans.

PMID- 19576250
TI  - Differential expression of mitogen-activated protein kinase signaling pathway in
      the hippocampus of rats exposed to chronic unpredictable stress.
AB  - Much research has indicated that the mitogen-activated protein kinase (MAPK)-cAMP
      response element-binding protein (CREB) signal transduction pathway is involved
      in the pathophysiological mechanism of depression. But as to the question of
      which MAPKs are more relevant to stress effects, there is no definite answer. In
      the present study, 32 male Sprague-Dawley rats were divided into chronic
      unpredictable stress (CUS) and control groups, with 16 rats in each group. The
      CUS rats were exposed to 21-day chronic unpredictable stressors, and the controls
      were stress-free. After stress, 16 rats (8 in each group) were tested for spatial
      memory using Morris Water Maze, and 16 rats (8 from each group) were decapitated
      for detection of the three most extensively studied subgroups of MAPKs, ERK1/2,
      JNK and P38, and CREB in the hippocampus. The results showed that there was no
      statistical difference in the body weight between the two groups. The CUS rats
      showed impaired spatial memory in MWM. Western blot of hippocampus showed that
      CUS significantly decreased pCREB and pJNK levels, but there was no statistical
      difference between two groups in CREB, ERK1/2, pERK1/2, P38, pP38 and JNK levels.
      Immunohistochemistry showed that the reduced pCREB occurred in the dentate gyrus,
      not in the hippocampus proper. In conclusion, this study highlights that the JNK
      CREB pathway, not the P38-CREB or ERK1/2-CREB pathway, in the hippocampus played
      an important role in the 21-day-CUS, and that the impaired spatial memory
      acquisition in the CUS rats can be restored to the level comparable to the pre
      stressed state.

PMID- 19576251
TI  - Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and
      post-translational modification of gliding-associated protein 45 (PfGAP45).
AB  - Plasmodium falciparum erythrocyte invasion is powered by an actin/myosin motor
      complex that is linked both to the tight junction and to the merozoite
      cytoskeleton through the Inner Membrane Complex (IMC). The IMC association of the
      myosin motor, PfMyoA, is maintained by its association with three proteins:
      PfMTIP, a myosin light chain, PfGAP45, an IMC peripheral membrane protein, and
      PfGAP50, an integral membrane protein of the IMC. This protein complex is
      referred to as the glideosome, and given its central role in erythrocyte
      invasion, this complex is likely the target of several specific regulatory
      effectors that ensure it is properly localized, assembled, and activated as the
      merozoite prepares to invade its target cell. However, little is known about how
      erythrocyte invasion as a whole is regulated, or about how or whether that
      regulation impacts the glideosome. Here we show that P. falciparum erythrocyte
      invasion is regulated by the release of intracellular calcium via the cyclic-ADP
      Ribose (cADPR) pathway, but that inhibition of cADPR-mediated calcium release
      does not affect PfGAP45 phosphorylation or glideosome association. By contrast,
      the serine/threonine kinase inhibitor, staurosporine, affects both PfGAP45
      isoform distribution and the integrity of the glideosome complex. This data
      identifies specific regulatory elements involved in controlling P. falciparum
      erythrocyte invasion and reveals that the assembly status of the merozoite
      glideosome, which is central to erythrocyte invasion, is surprisingly dynamic.

PMID- 19576252
TI  - Controlling subcellular localization to alter function: Sending oncogenic Bcr-Abl
      to the nucleus causes apoptosis.
AB  - Altering the subcellular localization of signal transducing proteins is a novel
      approach for therapeutic intervention. Mislocalization of tumor suppressors,
      oncogenes, or factors involved in apoptosis results in aberrant functioning of
      these proteins, leading to disease. In the case of chronic myelogenous leukemia
      (CML), cytoplasmic Bcr-Abl causes oncogenesis/proliferation. On the other hand,
      nuclear entrapment of endogenous Bcr-Abl (in K562 human leukemia cells) causes
      apoptosis. The goal of this study was to determine whether ectopically expressed
      Bcr-Abl could cause apoptosis of K562 cells when specifically directed to the
      nucleus via strong nuclear localization signals (NLSs). A single NLS from SV40
      large T-antigen or four NLSs were subcloned to Bcr-Abl (1NLS-Bcr-Abl or 4NLS-Bcr
      Abl). When transfected into K562 cells, only 4NLS-Bcr-Abl translocated to the
      nucleus. Bcr-Abl alone was found to localize in the cell cytoplasm, colocalizing
      with actin due to its actin binding domain. 1NLS-Bcr-Abl also localized with
      actin. Apoptosis induced by 4NLS-Bcr-Abl was evaluated 24h post-transfection by
      morphologic determination, DNA staining, and caspase-3 assay. This is the first
      demonstration that altering the location of ectopically expressed Bcr-Abl can
      kill leukemia cells. Multiple NLSs are required to overcome Bcr-Abl binding to
      actin, thus driving it into the nucleus and causing apoptosis.

PMID- 19576253
TI  - A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2
      expressing cells.
AB  - Tie2 receptor is a receptor tyrosine kinase that plays important roles in
      vascular angiogenesis, and also highly expressed by a number of cancer cells. In
      this study, we reported an active targeting liposome system directed by a novel
      peptide ligand PH1 that can improve drug efficacies specifically to Tie2
      expressing cells. The PH1 peptide (TMGFTAPRFPHY) was selected by phage display
      library screening combined with surface plasmon resonance binding assays. It was
      covalently conjugated to the distal end of DSPE-PEG(2000)-Maleimide lipid and
      loaded onto liposome membranes as the targeting ligand. These PH1-PEG-liposomes
      containing the anticancer drug cisplatin were showed to bind tightly to Tie2
      positive cells, mediate active endocytosis of the drug containing liposomes, and
      result in much higher cell specific cytoxicities than mPEG coated liposomes. They
      can be used not only to target vascular endothelial cells for anti-angiogenesis
      effects, but also to improve drug delivery and release in Tie2 expressing cancer
      cells. Such liposome formulation may be developed into a very useful agent for
      metronomic chemotherapy.

PMID- 19576254
TI  - Development and validation of the Infant Feeding Style Questionnaire.
AB  - This study describes and validates the Infant Feeding Style Questionnaire (IFSQ),
      a self-report instrument designed to measure feeding beliefs and behaviors among
      mothers of infants and young children. Categorical confirmatory factor analysis
      was used to estimate latent factors for five feeding styles, laissez-faire,
      restrictive, pressuring, responsive and indulgent, and to validate that items
      hypothesized a priori as measures of each style yielded well-fitting models.
      Models were tested and iteratively modified to determine the best fitting model
      for each of 13 feeding style sub-constructs, using a sample of 154 low-income
      African-American mothers of infants aged 3-20 months in North Carolina. With
      minor changes, models were confirmed in an independent sample of 150 African
      American first-time mothers, yielding a final instrument with 39 questions on
      maternal beliefs, 24 questions on behaviors and an additional 20 behavioral items
      pertaining to solid feeding for infants over 6 months of age. Internal
      reliability measures for the sub-constructs ranged from 0.75 to 0.95. Several sub
      constructs, responsive to satiety cues, pressuring with cereal, indulgent
      pampering and indulgent soothing, were inversely related to infant weight-for
      length z-score, providing initial support for the validity of this instrument for
      assessing maternal feeding beliefs and behaviors that may influence infant weight
      outcomes.

PMID- 19576255
TI  - The effect of exenatide re-exposure on safety and efficacy.
AB  - Exenatide, a synthetic peptide originally isolated from salivary secretions of
      Heloderma suspectum, like other subcutaneously injected peptides, can cause
      antibody formation. Despite that antibody formation has been observed in some
      patients, results from previous clinical trials have not shown safety and
      efficacy concerns in exenatide-naive patients. The objective of this multicenter,
      open-label study was to investigate the response of anti-exenatide antibody
      formation and the incidence of immune-related and hypersensitivity reactions
      after exenatide re-exposure. Fifty-eight patients (57% male; 59+/-10 years;
      weight 85+/-19kg; HbA1c 8.1+/-0.9%; duration of diabetes 10+/-5 years) were
      enrolled. At study initiation, 98.3% of patients were taking 1 or more
      antidiabetes drugs, including oral medication and various types of insulin.
      Treatment-emergent adverse events (TEAEs) at any time during the study were
      observed in 40 and 47% of patients with positive and negative treatment-emergent
      antibodies, respectively. Immune-related AEs were observed in 6 patients (4 were
      antibody positive). These AEs had not been reported in their previous exposure to
      exenatide. Re-exposure to exenatide did not result in increased hypersensitivity
      reactions. Overall, 72% of patients had a baseline to endpoint reduction in HbA1c
      (range -0.1 to -2.8%), and 87% of antibody negative versus 62% of antibody
      positive patients had an HbA1c endpoint reduction. The study design and the
      patients' baseline characteristics, including diabetes treatment at study
      initiation, are confounding factors limiting clinical conclusions on exenatide's
      glycemic effect in this patient population. The study results indicate that anti
      exenatide antibody formation did not increase the incidence of TEAEs in patients
      re-exposed to exenatide.

PMID- 19576256
TI  - Beta-casomorphins-7 in infants on different type of feeding and different levels
      of psychomotor development.
AB  - Casomorphins are the most important during the first year of life, when postnatal
      formation is most active and milk is the main source of both nutritive and
      biologically active material for infants. This study was conducted on a total of
      90 infants, of which 37 were fed with breast milk and 53 were fed with formula
      containing cow milk. The study has firstly indicated substances with
      immunoreactivity of human (irHCM) and bovine (irBCM) beta-casomorphins-7 in blood
      plasma of naturally and artificially fed infants, respectively. irHCM and irBCM
      were detected both in the morning before feeding (basal level), and 3h after
      feeding. Elevation of irHCM and irBCM levels after feeding was detected mainly in
      infants in the first 3 months of life. Chromatographic characterization of the
      material with irBCM has demonstrated that it has the same molecular mass and
      polarity as synthetic bovine beta-casomorphin-7. The highest basal irHCM was
      observed in breast-fed infants with normal psychomotor development and muscle
      tone. In contrast, elevated basal irBCM was found in formula-fed infants showing
      delay in psychomotor development and heightened muscle tone. Among formula-fed
      infants with normal development, the rate of this parameter directly correlated
      to basal irBCM. The data indicate that breast feeding has an advantage over
      artificial feeding for infants' development during the first year of life and
      support the hypothesis for deterioration of bovine casomorphin elimination as a
      risk factor for delay in psychomotor development and other diseases such as
      autism.

PMID- 19576258
TI  - Guanosine-5'-monophosphate induces cell death in rat hippocampal slices via
      ionotropic glutamate receptors activation and glutamate uptake inhibition.
AB  - Guanine derivatives modulate the glutamatergic system through displacement of
      binding of glutamate to its receptors acting as antagonist of glutamate receptors
      in moderate to high micromolar concentrations. Guanosine-5'-monophosphate (GMP)
      is shown to be neuroprotective against glutamate- or oxygen/glucose deprivation
      induced neurotoxicity and also against NMDA-induced apoptosis in hippocampal
      slices. However, in this study we are showing that high extracellular GMP
      concentrations (5mM) reduced cell viability in hippocampal brain slices. The
      toxic effect of GMP was not blocked by dipyridamole, a nucleoside transport
      inhibitor, nor mimicked by guanosine, suggesting an extracellular mode of action
      to GMP which does not involve its hydrolysis to guanosine. GMP-dependent cell
      damage was not blocked by P1 purinergic receptor antagonists, neither altered by
      adenosine A(1) or A(2A) receptor agonists. The blockage of the ionotropic
      glutamate receptors AMPA or NMDA, but not KA or metabotropic glutamate receptors,
      reversed the toxicity induced by GMP. GMP (5mM) induced a decrease in glutamate
      uptake into hippocampal slices, which was reversed by dl-TBOA. Therefore, GMP
      induced hippocampal cell damage involves activation of ionotropic glutamate
      receptors and inhibition of glutamate transporters activity.

PMID- 19576257
TI  - A role for Melanin-Concentrating Hormone in learning and memory.
AB  - The neurobiological substrate of learning process and persistent memory storage
      involves multiple brain areas. The neocortex and hippocampal formation are known
      as processing and storage sites for explicit memory, whereas the striatum,
      amygdala, neocortex and cerebellum support implicit memory. Synaptic plasticity,
      long-term changes in synaptic transmission efficacy and transient recruitment of
      intracellular signaling pathways in these brain areas have been proposed as
      possible mechanisms underlying short- and long-term memory retention. In addition
      to the classical neurotransmitters (glutamate, GABA), experimental evidence
      supports a role for neuropeptides in modulating memory processes. This review
      focuses on the role of the Melanin-Concentrating Hormone (MCH) and receptors on
      memory formation in animal studies. Possible mechanisms may involve direct MCH
      modulation of neural circuit activity that support memory storage and cognitive
      functions, as well as indirect effect on arousal.

PMID- 19576259
TI  - Protective role of melatonin against the mercury induced oxidative stress in the
      rat thyroid.
AB  - Present study investigated the protective role of melatonin (MLT, 5mg/kg body
      wt., ip) against the long term effects of mercuric chloride (MC; 2 and 4 mg/kg
      body wt., po) in the thyroid gland of the rats through certain antioxidative
      indices like superoxide dismutase (SOD), glutathione peroxidase (GPx),
      glutathione reductase (GR), glutathione (GSH), catalase (CAT) and lipid
      peroxidation (LPO), other biochemical parameters such as succinate dehydrogenase
      (SDH), adenosine triphosphatase (ATPase), acid phosphatase (ACPase) and alkaline
      phosphatase (ALPase) were also measured. Antioxidative enzymes and other
      parameters showed a significant reduction while LPO and mercury levels increased
      significantly in a dose dependent manner in MC treated animals as compared to
      control groups. Co-treatment with MLT revealed no significant effect on
      antioxidative and metabolic indices in the thyroid gland of rats. The results of
      present study thus strongly suggest that mercury affected antioxidant defense
      system and other metabolic enzymes of thyroid. Co-administration of melatonin
      exerted a protective effect against mercury induced endocrine toxicity.

PMID- 19576260
TI  - 90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil.
AB  - The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse
      mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat
      feeding study with in utero exposure. The results of the genotoxicity assays were
      all negative. The in utero phase of the 90-day study involved dietary exposure to
      0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a
      high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks
      prior to mating, through mating, gestation and lactation until offspring (F(1))
      weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same
      test and control diets. Statistically significant effects were seen for selected
      histopathology, clinical chemistry and organ weight endpoints; however, other
      than increased absolute and relative monocytes seen in both sexes of high-dose
      rats, the observations were not attributed to treatment for one or more reasons.
      Based on these findings, no adverse treatment-related effects for RAO were seen
      at up to 5% in the diet, equivalent to an overall average RAO intake of 3170
      mg/kg bwt/day. These and similar findings for other refined ARA-rich oils
      establish a strong body of evidence for the safety of this RAO.

PMID- 19576261
TI  - A prepared speech in front of a pre-recorded audience: subjective, physiological,
      and neuroendocrine responses to the Leiden Public Speaking Task.
AB  - This study describes a new public speaking protocol for youth. The main question
      asked whether a speech prepared at home and given in front of a pre-recorded
      audience creates a condition of social-evaluative threat. Findings showed that,
      on average, this task elicits a moderate stress response in a community sample of
      83 12- to 15-year-old adolescents. During the speech, participants reported
      feeling more nervous and having higher heart rate and sweatiness of the hands
      than at baseline or recovery. Likewise, physiological (heart rate and skin
      conductance) and neuroendocrine (cortisol) activity were higher during the speech
      than at baseline or recovery. Additionally, an anticipation effect was observed:
      baseline levels were higher than recovery levels for most variables. Taking the
      anticipation and speech response together, a substantial cortisol response was
      observed for 55% of participants. The findings indicate that the Leiden Public
      Speaking Task might be particularly suited to investigate individual differences
      in sensitivity to social-evaluative situations.

PMID- 19576262
TI  - Androgen receptor and 17beta-HSD type 2 regulation in neonatal mouse lung
      development.
AB  - A QPCR analysis of androgen receptor and several androgen metabolizing genes was
      performed during the saccular and alveolar stages of mouse lung development.
      Androgen receptor expression showed a statistically significant increase during
      the alveolar stage while levels of 17beta-hydroxysteroid dehydrogenase type 2
      (17beta-HSD 2) expression significantly decreased at the end of the saccular
      stage and remained low throughout the alveolar period. 17beta-HSD 1, 17beta-HSD
      5, 5alpha-reductase type 1, and mouse 3alpha-HSD did not present such a
      regulation. The androgen receptor protein was primarily detected in the nucleus
      of airway epithelial cells and of a subset of respiratory epithelial cells.
      17beta-HSD 2 mRNA co-localized with androgen receptor protein during
      saccularization, but was absent from airway epithelium during alveolarization.
      Taken together, our results demonstrate temporal and spatial regulation of
      androgen receptor and 17beta-HSD 2 during the sacculo-alveolar transition period
      of mouse lung development suggesting control of androgen action.

PMID- 19576263
TI  - Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting
      neuronal cell lines.
AB  - Kisspeptins, and their G-protein coupled receptor 54 (GPR54), are key components
      in the regulation of gonadotropin-releasing hormone (GnRH) secretion in humans
      and other mammals. Several studies demonstrate that the central or systemic
      administration of kisspeptin increases GnRH and gonadotropin secretion in both
      prepubertal and adult animals; however, the cellular targets and intracellular
      mechanisms of action in the central reproductive axis are unclear. In this study,
      we documented the presence of GPR54 in two GnRH secreting neuronal cell lines
      (GT1-7 and GN11). Kisspeptin treatment increases GnRH secretion and GnRH mRNA
      levels in a dose and time dependent manner. 10(-9)M kisspeptin maximally
      stimulated GnRH secretion by 2-fold and GnRH mRNA levels up to 4-fold after 4h of
      treatment in both cell lines. Negative regulation by 17beta-estradiol of GnRH
      secretion and GnRH mRNA was antagonized by kisspeptin. Co-treatment with
      kisspeptin and 17beta-estradiol increased GnRH secretion by 2-fold and GnRH mRNA
      by 4-fold over estradiol alone in both cell lines. Intracellular signaling
      pathway studies showed that an ERK1/2 MAPK inhibitor (PD98059) and a PI3K
      inhibitor, LY29402, attenuated the effects of kisspeptin on GnRH mRNA modulation.
      Furthermore, Western blot analysis showed that phosphorylation of both MAPK and
      Akt substrates increased with kisspeptin treatment. This work demonstrates that
      the kisspeptin-GPR54 system plays a significant role stimulating GnRH secretion
      and positive regulation of GnRH mRNA levels in GnRH neurons in culture, and also,
      demonstrates the activation of MAPK and Akt signaling pathways by kisspeptin in
      GT1-7 and GN11 cell lines.

PMID- 19576265
TI  - Coordinated multidisciplinary care for Huntington's disease. An outpatient
      department.
AB  - Huntington's disease is characterised by a complex set of motor, neuropsychologic
      and psychiatric symptoms which start slowly and progress over many years to a
      state of complete dependency. The symptomatic treatment during the ambulatory
      years is divers. In the northern part of the Netherlands coordinated
      multidisciplinary care is offered to patients diagnosed with Huntington's
      disease. A team of a neurologist, psychologist, occupational therapist, speech
      and language therapist, social worker and nursing home doctor monitors the
      patient and companion on a half-year basis and provide them with a plan of care.
      A case manager coordinates the plan of care in the dwelling place of the patient.
      In this article this type of care is outlined and illustrated with case
      histories.

PMID- 19576266
TI  - Neuropathology of Lewy body disorders.
AB  - The spectrum of Lewy body disorders includes not only Parkinson's disease,
      dementia with Lewy bodies and Parkinson's disease associated dementia but also
      Lewy body dysphagia and autonomic failure with Lewy bodies. In the last years an
      increasing number of cases showing Lewy body pathology has been recognised at
      autopsy. In fact, dementia with Lewy bodies is thought to be the second most
      frequent degenerative cause of cognitive decline in elderly after Alzheimer's
      disease, representing about 20% of dementia cases. The clinical diagnosis of
      dementia with Lewy bodies and of Parkinson's disease dementia is determinant for
      prognosis and therapeutic management, namely for avoiding increased sensibility
      to neuroleptics. The recent progress of neuropathology in this field made it
      possible to define clinical and neuropathological guidelines for the diagnosis.
      This review briefly describes the most important data of all Lewy body related
      disorders.

PMID- 19576264
TI  - Projections from auditory cortex to cholinergic cells in the midbrain tegmentum
      of guinea pigs.
AB  - Anterograde and retrograde tracing techniques were used to characterize
      projections from the auditory cortex to the pedunculopontine and laterodorsal
      tegmental nuclei (PPT and LDT, respectively) in the midbrain tegmentum in guinea
      pigs. For anterograde tracing, tetramethylrhodamine dextran (FluoroRuby) was
      injected at several sites within auditory cortex. After sufficient time for
      transport, the brain was processed for immunohistochemistry with anti-choline
      acetyltransferase to reveal presumptive cholinergic cells. Anterogradely labeled
      axons were observed ipsilaterally and, in smaller numbers, contralaterally, in
      both the pedunculopontine and laterodorsal tegmental nuclei. In all four nuclei,
      tracer-labeled boutons appeared to contact immunolabeled (i.e., cholinergic)
      cells. The contacts occurred on cell bodies and dendrites. The results were
      similar following injections that spread across multiple auditory cortical areas
      or injections that were within primary auditory cortex. In order to confirm the
      anterograde results, in a second series of experiments, retrograde tracers were
      deposited in the pedunculopontine tegmental nucleus. These injections labeled
      layer V pyramidal cells in the auditory cortex. The results suggest an excitatory
      projection from primary auditory cortex bilaterally to cholinergic cells in the
      midbrain tegmentum. Such a pathway could allow auditory cortex to activate
      brainstem cholinergic circuits, possibly including the cholinergic pathways
      associated with arousal and gating of acoustic stimuli.

PMID- 19576267
TI  - Rapid antidepressant effects of sleep deprivation therapy correlates with serum
      BDNF changes in major depression.
AB  - Recent reports have suggested that brain-derived neurotrophic factor (BDNF)
      levels are reduced in individuals suffering major depressive disorder and these
      levels normalize following antidepressant treatment. Various antidepressants and
      electroconvulsive therapy are shown to have a positive effect on brain-derived
      neurotrophic factor levels in depressive patients. The aim of this study was to
      assess the effect of total sleep deprivation therapy on BDNF levels in major
      depressive patients. Patients were assigned to two treatment groups which
      consisted of 22 patients in the sertraline group and 19 patients in the total
      sleep deprivation plus sertraline group. Patients in the sleep deprivation group
      were treated with three total sleep deprivations in the first week of their
      treatment and received sertraline. Patients in sertraline group received only
      sertraline. BDNF levels were measured in the two treatment groups at baseline,
      7th, 14th, and 42nd days. Patients were also evaluated using the Hamilton Rating
      Scale for Depression (HAM-D). A control group, consisting of 33 healthy
      volunteers had total sleep deprivation, BDNF levels and depression measured at
      baseline and after the total sleep deprivation. Results showed that serum BDNF
      levels were significantly lower at baseline in both treatment groups compared to
      controls. Decreased levels of BDNF were also negatively correlated with HAM-D
      scores. First single sleep deprivation and a series of three sleep deprivations
      accelerated the treatment response that significantly decreased HAM-D scores and
      increased BDNF levels. Total sleep deprivation and sertraline therapy is
      introduced to correlate with the rapid treatment response and BDNF changes in
      this study.

PMID- 19576269
TI  - Prevention of age-associated dementia.
AB  - The advancement of medical sciences during the last century has resulted in a
      considerable increase in life expectancy. As more people live to old age, one of
      the most fundamental questions of the 21st century is whether the number of
      individuals suffering from dementia will also continue to increase. Alzheimer's
      disease (AD) accounts for the majority of cases of dementia in the elderly, but
      there is currently no curative treatment available. Several strategies have been
      introduced for treatment, the most recent strategy of which was the immunization
      of patients using antibodies against Abeta, which is a naturally occurring, even
      though misfolded peptide in the AD brain. Both active and passive immunization
      routes have been shown to reduce the pathology associated with Abeta accumulation
      in brains of genetically designed animal models. However, despite tremendous
      efforts, no unequivocal proof of therapeutic efficacy could be shown in AD
      patients. Particularly, the persistence of the neurofibrillary tangles in
      immunized brains and the issue of inducing cerebral amyloid angiopathy are major
      limiting factors of antibody therapy. Furthermore, physical activity, a healthy
      immune system and nutritional habits are suggested to protect against the onset
      of age-associated dementia. Thus, accumulative evidence suggests that an early
      integrated strategy, combining pharmacological, immunological, nutritional and
      life-style factors, is the most pragmatic approach to delay the onset and
      progression of age-associated dementia.

PMID- 19576268
TI  - Salt taste inhibition by cathodal current.
AB  - Effects of cathodal current, which draws cations away from the tongue and drives
      anions toward the tongue, depend on the ionic content of electrolytes through
      which the current is passed. To address the role of cations and anions in human
      salt tastes, cathodal currents of -40 microA to -80 microA were applied to human
      subjects' tongues through supra-threshold salt solutions. The salts were sodium
      chloride, sodium bromide, potassium chloride, ammonium chloride, calcium
      chloride, sodium nitrate, sodium sulfate, sodium saccharin, sodium acetate and
      sodium benzoate, which taken together encompass salty, bitter, sour and sweet
      taste qualities. The taste of NaCl, the salty and bitter tastes of the other
      chloride salts and the taste of NaNO(3) was inhibited, suggesting the current
      displaced stimulatory cations from salty and bitter receptors. However, bitter
      tastes of non-halide sodium salts were not inhibited, likely because other bitter
      receptors respond to anions. A discharge current at cathode-off ubiquitously
      evoked a metallic taste reminiscent of anodal taste used in clinical
      electrogustometry. Analogous effects on ambient NaCl responses were recorded from
      the hamster chorda tympani nerve. Increases in tastes of the saccharin and
      benzoate anions were not evoked during current flow, suggesting that cathodal
      current does not carry stimulatory anions to sweet receptors. Cathodal current
      may selectively inhibit salty and bitter-salty tastes for which proximal stimuli
      are cations.

PMID- 19576270
TI  - Colocalization of neuropeptides with calcium-binding proteins in the claustral
      interneurons during postnatal development of the rat.
AB  - The claustrum is a relatively large telencephalic structure, situated close to
      the border of the neo- and allocortical regions. Its neuronal population consists
      of glutamatergic, projecting neurons and GABA-ergic interneurons, characterized
      by occurrence of numerous additional biochemical markers. The postnatal
      development of these latter neurons has not been extensively studied. Revealing
      the characteristic patterns of colocalizations between selected markers may shed
      some light on their function and origin. We investigated the colocalization
      patterns between three neuropeptides: neuropeptide Y, somatostatin, vasoactive
      intestinal polypeptide and three calcium-binding proteins: calbindin D28k,
      calretinin, parvalbumin in the interneurons of the rat claustrum during a four
      month postnatal period (P0-P120; P: postnatal day). Our studies revealed the
      following types of colocalizations: neuropeptide Y with calbindin D28k,
      calretinin or parvalbumin; somatostatin with calbindin D28k; vasoactive
      intestinal polypeptide with calretinin. Only vasoactive intestinal polypeptide-
      and calretinin-containing, double-labeled neurons were present at the day of
      birth, whereas the other double-labeled neurons appeared at later stages of
      development. The ratios of colocalizing neurons to single-labeled neurons in each
      type of colocalization were differentiated and reached the highest value (51%)
      for vasoactive intestinal polypeptide- and calretinin-double-labeled neurons. In
      conclusion, the claustral interneurons represent differentiated population in
      respect to the occurrence of neuropeptides and calcium-binding proteins. The
      expression of studied substances is changing during the postnatal period.

PMID- 19576271
TI  - Effects of anti-histaminic and anti-cholinergic substances on human
      thermoregulation during cold provocation.
AB  - The roles of histaminergic and cholinergic neuron systems in the regulation of
      body temperature have been studied almost exclusively in animals. Recently, we
      have found that motion sickness, i.e. a condition where hippocampal cholinergic
      mismatch signals induce a release of histamine in the vomiting centre,
      accelerates the decline in body temperature in men during exposure to cold. In
      the present study we measured the thermoregulatory effects of two substances
      commonly used against motion sickness, i.e. the histamine (H1) receptor blocker
      dimenhydrinate (DMH) and the muscarine receptor blocker scopolamine (SCOP). In
      three trials, control (CN), DMH and SCOP, 10 male subjects were immersed in 15
      degrees C water for a maximum of 90 min. The trials were separated by a minimum
      of three days and their order was alternated between subjects. In all trials the
      subject received, in a double blind fashion, a transdermal patch (SCOP or
      placebo) 12-14 h before immersion and a tablet (DMH or placebo) 1h before
      immersion. Mean skin temperature, rectal temperature (T(rec)), the difference in
      temperature between the non-immersed right forearm and 3rd finger of the right
      hand (T(ff)), and oxygen uptake (VO(2)) were recorded. The fall in T(rec) was
      smaller in the DMH than in the CN and SCOP conditions. The recordings of T(ff)
      and VO(2) suggest that SCOP attenuates peripheral vasoconstriction while DMH
      increases shivering thermogenesis. Notably, thermal discomfort was reduced in the
      SCOP condition. Findings are thoroughly discussed in the context of animal
      studies on the neuropharmacology and neurophysiology of thermoregulation and
      motion sickness.

PMID- 19576272
TI  - Neuroprotective treatment strategies for poststroke mood disorders: A minireview
      on atypical neuroleptic drugs and selective serotonin re-uptake inhibitors.
AB  - In our minireview we summarize the neuroprotective effect of atypical
      antipsychotic and selective serotonin re-uptake inhibitors after cerebral
      ischemia. In regard of increasing rate of poststroke mood disorders and current
      evidences indicating to an increased rate of cerebrovascular accidents after
      neuroleptic usage by the elderly population we also reviewed the clinical
      relevance of the neuroprotective and mood stabilizing effect of atypical
      antipsychotic agents in the light of basic pathophysiology of stroke.

PMID- 19576273
TI  - Encoding of relative enclosure size in a dynamic three-dimensional virtual
      environment by humans.
AB  - Human participants searched in a dynamic three-dimensional virtual-environment
      rectangular enclosure for a distinctly colored bin located in one of the four
      corners. During test trials, all bins were rendered identical in color, and the
      shape of the rectangular search space either remained the same or was modified to
      a relatively sized contracted rectangle, an expanded rectangle, or a square.
      Participants made one choice response during test trials. In the rectangular
      enclosures, more of participants' choice responses were allocated to the
      geometrically correct corners than to the geometrically incorrect corners. In the
      square enclosure, participants' choice responses were allocated equivalently to
      each of the four corners. Results replicate previous enclosure size studies
      demonstrating encoding of enclosure geometry with human and non-human animal
      subjects conducted in real environments and extend these results to include
      encoding of relative enclosure geometry. Results are discussed with respect to
      theoretical accounts of geometry learning.

PMID- 19576274
TI  - Differences in cue-dependent spatial navigation may be revealed by in-depth
      swimming analysis.
AB  - Several factors can influence allocentric navigation in the Morris water maze
      (MWM), including the number of available distal visual cues. Using in-depth
      analytical measures investigating platform-based and swimming behaviour, we
      examine and compare animals exposed to either one or three distal visual cues
      during MWM acquisition. We demonstrate that, although animals exposed to one cue
      can acquire the task as well as those in a multiple cue condition, several subtle
      differences between the groups' swimming behaviours are noted. Both groups
      actively use cues to guide them to the platform, but changing the number of cues
      alters the animals' patterns of behaviour, wherein exposure to a single cue leads
      to a simpler strategy in which the cue appears to act as a beacon for navigation.

PMID- 19576275
TI  - Uptake of permethrin from impregnated clothing.
AB  - In order to examine exposure and health risks which can arise from permethrin
      impregnated clothing, a controlled trial was conducted. In a study group
      consisting of 187 volunteers in total, a subgroup of 86 persons was equipped with
      permethrin-impregnated battle dress uniforms (BDU) for 28 days. One hundred and
      one persons served as a control group, wearing non-impregnated BDUs throughout
      the entire study period of 56 days. Internal exposure of all participants was
      assessed by determination of urinary permethrin metabolites (cis-DCCA, trans-DCCA
      and 3-PBA) on day 0, 14 and 28 of the wearing period and 28 days after
      termination of wearing. Exposure levels in the control group ranged within
      background exposure of the general German population at all four dates of
      sampling (medians Sigma DCCA+3-PBA were 0.09, 0.13, 0.23 and 0.10mug/l,
      respectively). For the group equipped with impregnated BDUs this applied to day 0
      (0.31mug/l) only, while the following measurements revealed considerably higher
      metabolite concentrations (31.39, 22.01 and 1.44mug/l, respectively), especially
      while wearing impregnated clothing. Due to these results a substantial uptake of
      permethrin from impregnated BDUs has to be assumed. However, since calculations
      reveal a maximum permethrin uptake clearly below the acceptable daily intake
      (ADI), health impairments are rather unlikely.

PMID- 19576276
TI  - Fire fighting trainers' exposure to carcinogenic agents in smoke diving
      simulators.
AB  - It is well known that fire fighters are potentially exposed to various
      carcinogenic agents at a fire scene. An almost unheeded issue, however, is fire
      fighters' exposure to carcinogenic agents in smoke diving simulators.
      Biomonitoring (urinary muconic acid, 1-naphthol and 1-pyrenol), dermal
      (polycyclic aromatic hydrocarbons) and occupational hygiene measurements
      (cyanides, hydrogen cyanide, polycyclic aromatic hydrocarbons, volatile organic
      compounds and formaldehyde) were used to determine how the burning material, the
      type of simulator and protective clothing used affect fire fighting trainers'
      exposure. The highest excretion of 1-pyrenol (sampled 6h after end of exposure,
      in average 4.3-9.2nmol/L) and emissions of benzene (1.0-2.5mg/m(3)) and hydrogen
      cyanide (0.2-0.9mg/m(3)) were measured during the burning of conifer plywood and
      chipboard, and the lowest when pure pine and spruce wood (1.5nmol/L, 0.6mg/m(3),
      and 0.05mg/m(3)) was burned. However the safest burning material seemed to be
      propane (1.0nmol/L, 0.2mg/m(3), and not measured). The type of simulator used
      affected trainers' exposure very clearly. The highest dermal whole body exposures
      to polycyclic aromatic hydrocarbons were measured in the fire house simulator (in
      average 1200ng/cm(2)). Clearly lower exposure levels were measured in container
      training sessions (760ng/cm(2)), where the average dermal exposure level was 35%
      lower than in the fire house. The exposure levels (30ng/cm(2)) in the gas
      simulator in turn, were only 4% of the levels in container training sessions. The
      amount of polycyclic aromatic hydrocarbons decreased by 80% on trainers' hands
      when they used under gloves (in average 8.7ng/cm(2)) compared to those
      (48.4ng/cm(2)) who did not. There was not difference in protection efficiency
      against polycyclic aromatic hydrocarbons between tested fire suits (Brage and
      Bristol).

PMID- 19576277
TI  - Bioavailability of sodium nitrite from an aqueous solution in healthy adults.
AB  - Nitrate intake in humans is high through intake of vegetables such as beets,
      lettuce, and spinach. Nitrate itself is a compound of low toxicity but its
      metabolite, nitrite, formed by bacteria in the oral cavity and gastrointestinal
      tract, has been suspected of potential carcinogenic effects. Nitrite can induce
      systemic toxicity only after having been absorbed from the gastrointestinal
      tract. The aim of this study was to determine the absolute bioavailability of
      nitrite following oral administration in humans. In an open, three-way cross-over
      study, nine subjects received two single oral doses of sodium nitrite (0.12 and
      0.06 mmol NaNO(2)/mmol Hb) and one intravenous sodium nitrite dose (0.12 mmol
      NaNO(2)/mmol Hb). Plasma samples were analysed to assess the nitrite levels, and
      pharmacokinetic parameters were calculated. Nitrate and methaemoglobin levels in
      plasma were also measured as oxidation of nitrite results in the formation of
      these two compounds. Absolute bioavailability of nitrite was 98% after oral
      administration of 0.12 mmol NaNO(2)/mmol Hb, and 95% after oral administration of
      0.06 mmol NaNO(2)/mmol Hb. Minor adverse effects were observed after the 0.12
      mmol NaNO(2)/mmol Hb oral dose. In conclusion, nitrite in solution is highly
      absorbed from the gastrointestinal tract and the first pass effect in the liver
      is low.

PMID- 19576278
TI  - Plants as bioreactors: Recent developments and emerging opportunities.
AB  - In recent years, the use of plants as bioreactors has emerged as an exciting area
      of research and significant advances have created new opportunities. The driving
      forces behind the rapid growth of plant bioreactors include low production cost,
      product safety and easy scale up. As the yield and concentration of a product is
      crucial for commercial viability, several strategies have been developed to boost
      up protein expression in transgenic plants. Augmenting tissue-specific
      transcription, elevating transcript stability, tissue-specific targeting,
      translation optimization and sub-cellular accumulation are some of the strategies
      employed. Various kinds of products that are currently being produced in plants
      include vaccine antigens, medical diagnostics proteins, industrial and
      pharmaceutical proteins, nutritional supplements like minerals, vitamins,
      carbohydrates and biopolymers. A large number of plant-derived recombinant
      proteins have reached advanced clinical trials. A few of these products have
      already been introduced in the market.

PMID- 19576279
TI  - Increased apoptosis and reduced neuronal and glial densities in the hippocampus
      due to nicotine and ethanol exposure in adolescent mice.
AB  - It has been recently shown that nicotine and ethanol interact during adolescence
      affecting memory/learning and anxiety levels. Considering the role of the
      hippocampus in both anxiety and memory/learning, we investigated whether
      adolescent nicotine and/or ethanol administration elicit apoptotic cell death and
      whether this results in neuronal and/or glial density alterations in the
      following regions of the hippocampus: granular layer of the dentate gyrus (GrDG),
      molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day,
      C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or
      ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50mug/ml in 2%
      saccharin to drink) and ETOH (25%, 2g/kg i.p. injected every other day) exposure;
      (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell degeneration
      (TUNEL assay), neuronal and glial densities (optical disector) and region
      thicknesses at the end of the period of exposure. Our results demonstrate that
      ETOH elicited an increase in TUNEL-positive cells relative to the vehicle group
      in all hippocampal regions. NIC elicited less severe region-dependent effects:
      the number of TUNEL-positive cells was significantly increased in the Mol and CA1
      when compared to the vehicle group. These results were paralleled by reductions
      in neuronal and glial cells densities, which indicate that both cell types are
      sensitive to the neurotoxic effects of these drugs. There were no effects on
      region thicknesses. On the other hand, concomitant NIC and ETOH reduced the
      adverse effects of the drugs when administered separately. This ability of
      nicotine and ethanol co-exposure to lessen the adverse effects of nicotine and
      ethanol may contribute to adolescents co-use and co-abuse of tobacco and
      alcoholic beverages.

PMID- 19576280
TI  - alpha-Hydroxynitrile lyase protein from Xylella fastidiosa: Cloning, expression,
      and characterization.
AB  - Xylella fastidiosa is a xylem-restricted plant pathogen that causes a range of
      diseases in several and important crops. Through comparative genomic sequence
      analysis many genes were identified and, among them, several potentially involved
      in plant-pathogen interaction. The experimental determination of the primary
      sequence of some markedly expressed proteins for X. fastidiosa and the comparison
      with the nucleic acids sequence of genome identified one of them as being
      SCJ21.16 (XFa0032) gene product. The comparative analysis of this protein against
      SWISSPROT database, in special, resulted in similarity with alpha-hydroxynitrile
      lyase enzyme (HNL) from Arabidopsis thaliana, causing interest for being one of
      the most abundant proteins both in the whole cell extract as well as in the
      extracellular protein fraction. It is known that HNL enzyme are involved in a
      process termed "cyanogenesis", which catalyzes the dissociation of alpha
      hydroxinitrile into carbonyle and HCN when plant tissue is damaged. Although the
      complete genome sequences of X. fastidiosa are available and the cyanogenesis
      process is well known, the biological role of this protein in this organism is
      not yet functionally characterized. In this study we presented the cloning,
      expression, characterization of recombinant HNL from X. fastidiosa, and its
      probable function in the cellular metabolism. The successful cloning and
      heterologous expression in Escherichia coli resulted in a satisfactory amount of
      the recombinant HNL expressed in a soluble, and active form giving convenient
      access to pure enzyme for biochemical and structural studies. Finally, our
      results confirmed that the product of the gene XFa0032 can be positively assigned
      as FAD-independent HNLs.

PMID- 19576281
TI  - In vitro/in vivo phototoxic risk assessments of griseofulvin based on
      photobiochemical and pharmacokinetic behaviors.
AB  - The present investigation aims to establish efficacious screening strategy to
      clarify the phototoxic potential of pharmaceutical substances and its possible
      pathways by characterizing both photobiochemical properties and pharmacokinetic
      profiles. Photochemical behavior of griseofulvin, as model compounds, was
      evaluated by reactive oxygen species (ROS) assay, and the photogenotoxic
      potential was also assessed by DNA binding assay, DNA photocleavage assay, and
      atomic force microscopy. Pharmacokinetic (PK) study was also carried out after
      dermal and oral administration of griseofulvin in rats. ROS assay suggested the
      phototoxic potential of griseofulvin via type II photochemical pathways, and the
      photogenotoxic risk of griseofulvin was also proposed as evidenced by high
      affinity toward DNA and potent DNA photocleaving activity. PK profiling and in
      vivo phototoxicity testing demonstrated that a highly concentrated griseofulvin
      in the skin might cause phototoxic skin reactions in rats, whereas oral
      administration of griseofulvin in single dosing regimen (20mg/kg) resulted in
      10(3)-fold less skin deposition than phototoxic skin concentration of
      griseofulvin. Upon these findings, the phototoxic potential of griseofulvin might
      not be severe at least in a single oral dosing regimen, whereas it might be
      phototoxic in dermal administration. The combination use of photobiochemical and
      pharmacokinetic data would be valuable to provide reliable prediction on
      phototoxic risk and possible toxic pathways of new drug entities in the early
      stage of drug discovery.

PMID- 19576282
TI  - Transport of a hyaluronan-binding protein in brain tissue.
AB  - Hyaluronan is an unsulfated linear glycosaminoglycan with the ability to nucleate
      extracellular matrices by the formation of aggregates with lecticans. These
      matrices are essential during development of the central nervous system. In the
      prospective white matter of the developing brain hyaluronan is organized into
      fiber-like structures according to confocal microscopy of fixed slices which may
      guide the migration of neural precursor cells [Baier, C., S.L. Baader, J.
      Jankowski, V. Gieselmann, K. Schilling, U. Rauch, and J. Kappler. 2007.
      Hyaluronan is organized into fiber-like structures along migratory pathways in
      the developing mouse cerebellum. Matrix Biol. 26: 348-58]. By using plasmon
      surface resonance, microinjection into brain slices and fluorescence correlation
      spectroscopy, we show that the brain-specific lecticans bind to, but also
      dissociate rather rapidly from hyaluronan. After microinjection into native
      cerebellar slices a GFP-tagged hyaluronan-binding neurocan fragment was enriched
      at binding sites in the prospective white matter, which had a directional
      orientation and formed local stationary concentration gradients in areas where
      binding sites are abundant. Fluorescence correlation spectroscopy measurements at
      fixed brain slices revealed that fiber-bound neurocan-GFP was mobile with
      D(fiber(neurocan-GFP))=4x10(-10)cm(2)/s. Therefore, we propose that hyaluronan
      rich fibers in the prospective white matter of the developing mouse cerebellum
      can guide the diffusion of lecticans. Since lecticans bind a variety of growth
      and mobility factors, their guided diffusion may contribute to the transport of
      these polypeptides and to the formation of concentration gradients. This
      mechanism could serve to encode positional information during development.

PMID- 19576283
TI  - Conformation and topology of amyloid beta-protein adsorbed on a tethered
      artificial membrane probed by surface plasmon field-enhanced fluorescence
      spectroscopy.
AB  - Progressive depositions of cerebral amyloid are primary neuropathologic features
      of Alzheimer's disease (AD). The amyloid is composed of a 39-42 amino acid
      peptide called the amyloid beta-protein (Abeta). Repeated investigation suggests
      that the conformational transition of Abeta from alpha-helix or random coil to
      beta-sheet structure plays a key role in the inappropriate accumulation of
      cerebral amyloid plaques. In this manuscript, we describe a fluorescence-based
      immunoassay technology to investigate the conformation and topology of Abeta
      peptides interacting with peptide-tethered planar lipid bilayers. Dual monoclonal
      antibodies (mAbs) labelled with fluorophores were employed to recognise a linear
      N- and a beta-sheet C-terminus of Abeta peptides on the model membrane,
      respectively. Kinetics of antibody-Abeta binding were determined by surface
      plasmon field-enhanced fluorescence spectroscopy (SPFS). The conformational
      transition of Abeta by melatonin, a defined beta-sheet breaker, was probed using
      paired monoclonal antibodies. The Abeta interaction with the membrane was
      evaluated by carefully analyzing the change in kinetic/affinity parameters in the
      presence or absence of melatonin. These results show that SPFS can be used to
      examine conformational transition of Abeta on an artificial membrane, providing a
      novel and versatile platform for conveniently monitoring protein-membrane
      interaction and screening for new beta-sheet breakers.

PMID- 19576284
TI  - Internodal myelination during development quantitated using X-ray diffraction.
AB  - Characterizing the formation, accretion, and stability of myelin during
      development, maturation, and senescence is important for better understanding
      critical periods in the function of the nervous system in normal growth and
      following environmental insult or genetic mutation. Although there are numerous
      studies on the ultrastructural, biochemical, and genetic aspects of myelin
      development and maturation, few have used X-ray diffraction (XRD), which can
      rapidly provide unique metrics about internodal myelin based on measurements from
      whole, unfixed tissue. Besides periodicity (the classic attribute of internodal
      myelin measured by XRD), other parameters include: relative amount of myelin,
      membrane dimensions, and packing disorder. To provide a baseline for future
      experiments on myelin structural integrity, we used XRD to characterize
      internodal myelin as a function of age (from 5 to 495 days) in the mouse, a
      species increasingly used for developing transgenic models of human neurological
      diseases. As expected, the relative amount of myelin increased with age in both
      PNS and CNS, with the most rapid accumulation occurring in the youngest age
      group. Changes in rate of myelin accretion yielded three distinct age brackets
      during which small but significant changes in structural parameters were
      detected: in PNS, myelin period increased, packing distortion decreased, width of
      extracellular apposition (EXT) decreased, and widths of cytoplasmic apposition
      (CYT) and lipid bilayer (LPG) increased; in CNS, myelin period decreased, packing
      distortion decreased, EXT and CYT decreased, and LPG increased. We propose that
      the data obtained here can serve as a basis for rapidly detecting abnormal
      pathologies during myelination.

PMID- 19576285
TI  - A novel Fas ligand in mollusk abalone: molecular characterization, immune
      responses and biological activity of the recombinant protein.
AB  - Fas ligand is a member of the TNF superfamily that plays an important role by
      inducing apoptosis and homeostasis of immune responses. The gene encoding Fas
      ligand was isolated from a disk abalone (Haliotis discus discus) cDNA library,
      denoted as the AbFas ligand. It contains an 1832bp transcript with a 945bp open
      reading frame, encoding 315 amino acids. The AbFas ligand showed characteristic
      transmembrane and TNF family signature domains. The deduced amino acid comparison
      showed that the AbFas ligand exhibits 22.0, 16.1 and 14.5% identities to human
      Fas ligand, TNF-alpha, and lymphotoxin (LT-alpha), respectively. Phylogenetic
      analysis indicates that the AbFas ligand belongs to the invertebrate TNF family
      and it is closely related to vertebrate Fas ligand counterparts. Quantitative
      real-time PCR analysis results showed that the AbFas ligand transcripts were
      constitutively expressed in abalone hemocytes, gills, mantle, muscle, digestive
      tract and digestive gland in a tissue-specific manner. By immune stimulation,
      AbFas ligand mRNA was significantly (p<0.05) up-regulated after infection with a
      mixture of bacteria (Vibrio alginolyticus, Vibrio parahemolyticus, and Listeria
      monocytogenes), viral haemorrhagic septicaemia virus (VHSV), and
      lipopolysaccharide (LPS) in abalone gills. The recombinant AbFas ligand was over
      expressed in Escherichia coli (E. coli) and purified using a pMAL protein fusion
      system. This recombinant AbFas ligand showed its biological activity by inducing
      both superoxide anion (O(2-) and H(2)O(2) in human THP-1 cells in concentration
      dependant manner. Correlating the AbFas ligand transcriptional up-regulation
      against bacteria, virus and LPS with the biological activity of its recombinant
      protein, we could suggest that the abalone Fas ligand may control microbial
      infection by inducing O(2-), H(2)O(2) and other ROS.

PMID- 19576286
TI  - Penaeus monodon chitin-binding protein (PmCBP) is involved in white spot syndrome
      virus (WSSV) infection.
AB  - White spot syndrome virus (WSSV) can cause the most serious viral disease of
      shrimp and has a wide host range among crustaceans. Although researches show a
      lot about its genome and structure, information concerning the mechanism of how
      WSSV infects' cells is lacking. In this study, some experiments were applied to
      confirm the biological meaning of the protein-protein interaction between WSSV
      envelope protein, VP53A, and Penaeus monodon chitin-binding protein (PmCBP).
      Immunofluorescent study indicated that PmCBP is located on the cell surface of
      host cells. PmCBP amounts of about 34kDa can be detected in both P. monodon and
      Litopenaeus vannamei tissues by Western blotting. In the in vivo neutralization
      experiment, both rVP53A and rPmCBP that were produced by Esherichia coli can
      promote resp. a 40% and 20% survival rate of the shrimp which were challenged by
      WSSV. Furthermore, a yeast-two-hybrid result revealed that PmCBP could interact
      with at least 11 WSSV envelope proteins. Those findings suggest that PmCBP may be
      involved in WSSV infection.

PMID- 19576288
TI  - Pentylenetetrazole as an unconditioned stimulus for olfactory and contextual fear
      conditioning in rats.
AB  - The association of five footshocks with a neutral odor is able to establish an
      olfactory fear conditioning in rats. The present study sought to investigate
      whether the systemic administration of pentylenetetrazole (PTZ; 3.75-15 mg/kg)
      would turn the coffee odor in a conditioned stimulus in the fear conditioning
      paradigm. The results showed that rats started to display risk assessment and
      avoidance after PTZ (15 mg/kg)-coffee odor pairing. When three mild footshocks
      (0.4 mA for 2 s) were delivered during this pairing, the conditioned response
      exhibited was greater than before. In both cases, however, pretreatment with the
      benzodiazepine midazolam (MDZ. 0.5 mg/kg i.p.) fully counteracted the expression
      of these defensive behaviors. Moreover, after being paired with 15 mg/kg of PTZ
      alone or combined with footshocks, the coffee odor was able to promote a new fear
      conditioning related to the context where it was re-exposed. The present findings
      point out the usefulness of PTZ as an unconditioned stimulus to promote fear
      conditioning to olfactory and contextual cues in rats.

PMID- 19576287
TI  - Altered neurometabolites and motor integration in children exposed to
      methamphetamine in utero.
AB  - Methamphetamine (METH) is a neurotoxic drug. This study aimed to evaluate brain
      metabolite levels and cognitive function in young children with prenatal METH
      exposure. 101 children ages 3-4 years were evaluated with neuropsychological
      tests and underwent proton magnetic resonance spectroscopy ((1)H-MRS) without
      sedation. Complete datasets from 49 METH-exposed and 49 controls who completed
      the neuropsychological test battery, and 38 METH-exposed and 37 controls with
      high-quality MR spectra are reported here. Despite similar physical
      characteristics (including head circumference), global cognitive function (on
      Stanford-Binet), parental education, intelligence, mood, and socioeconomic
      status, METH-exposed children had higher total creatine (tCr: +7%, p=0.003), N
      acetyl compounds (NA: +4.3%, p=0.004) and glutamate+glutamine (GLX: +9.6%,
      p=0.02) concentrations in the frontal white matter, but lower myoinositol (MI: 
      7%, p=0.01) and MI/tCr (-7.5%, p=0.03) in the thalamus, than control children.
      The higher frontal white matter NA in the METH-exposed children was due to the
      higher NA in the METH-exposed girls (+10.2%, p=0.003), but not the boys (+0.8%)
      compared to sex-matched controls. Furthermore, the METH-exposed children had
      poorer performance on a visual motor integration (VMI) task, which correlated
      with lower MI in the thalamus (r=0.26, p=0.03). The higher NA, tCr and GLX
      concentrations suggest higher neuronal density or cellular compactness in the
      white matter, especially in the girls, whereas the lower MI suggests lower glial
      content in the thalamus of these METH-expose children. These findings combined
      with their poorer performance on VMI also suggest accelerated but aberrant
      neuronal and glial development in these brain regions.

PMID- 19576289
TI  - Dysgonomonas hofstadii sp. nov., isolated from a human clinical source.
AB  - A Gram-negative staining, facultative anaerobic, cocco-bacillus-shaped organism
      was isolated from a post-operative abdominal wound. Based on morphological and
      biochemical criteria, strain MX 1040 (=CCUG 54731(T)) was tentatively identified
      as Bacteroidaceae but did not correspond to any recognized species of this
      family. Comparative 16S rRNA gene sequencing analysis demonstrated the organism
      to be related to species of the genus Dysgonomonas, although sequence divergence
      values of >5% with the other members of this genus demonstrated the organism to
      represent a novel species. Phylogenetic analysis revealed the novel organism to
      be most closely related to Dysgonomonas gadei. The major long-chain cellular
      fatty acids of the novel species consisted of iso-C(14:0), anteiso-C(15:0),
      C(16:0), and iso-C(16:0). Based on the phenotypic criteria and phylogenetic
      considerations, it is proposed that strain MX 1040 from a human clinical source
      represents a new species of the genus Dysgonomonas, as Dysgonomonas hofstadii sp.
      nov. The type strain of D. hofstadii is CCUG 54731(T) (=CCM 7606(T)).

PMID- 19576290
TI  - Nitrite reduction and superoxide-dependent nitric oxide degradation by
      Arabidopsis mitochondria: influence of external NAD(P)H dehydrogenases and
      alternative oxidase in the control of nitric oxide levels.
AB  - Mitochondria recently have emerged as important sites in controlling NO levels
      within the cell. In this study, the synthesis of nitric oxide (NO) from nitrite
      and its degradation by mitochondria isolated from Arabidopsis thaliana were
      examined. Oxygen and NO concentrations in the reaction medium were measured with
      specific electrodes. Nitrite inhibited the respiration of isolated A. thaliana
      mitochondria, in competition with oxygen, an effect that was abolished or
      potentiated when electron flow occurred via alternative oxidase (AOX) or
      cytochrome c oxidase (COX), respectively. The production of NO from nitrite was
      detected electrochemically only under anaerobiosis because of a superoxide
      dependent process of NO degradation. Electron leakage from external NAD(P)H
      dehydrogenases contributed the most to NO degradation as higher rates of Amplex
      Red-detected H(2)O(2) production and NO consumption were observed in NAD(P)H
      energized mitochondria. Conversely, the NO-insensitive AOX diminished electron
      leakage from the respiratory chain, allowing the increase of NO half-life without
      interrupting oxygen consumption. These results show that the accumulation of
      nitric oxide derived from nitrite reduction and the superoxide-dependent
      mechanism of NO degradation in isolated A. thaliana mitochondria are influenced
      by the external NAD(P)H dehydrogenases and AOX, revealing a role for these
      alternative proteins of the mitochondrial respiratory chain in the control of NO
      levels in plant cells.

PMID- 19576291
TI  - Effects of vitamin B1 (thiamine) deficiency in lake trout (Salvelinus namaycush)
      alevins at hatching stage.
AB  - The objectives of this study were to examine the relationship between thiamine
      concentrations in unfertilized eggs and yolksac individuals of lake trout
      (Salvelinus namaycush), along with any associated histopathological changes in
      the tissues of alevins at the hatching stage. We address these questions in a
      lake trout population from different spawning grounds of Lake Michigan (North and
      South), known for compromised survival due to early mortality syndrome (EMS).
      However, a dichotomous forage base of lake trout spawning stocks, with a dietary
      thiaminase-rich alewife in the North, and dietary low-thiaminase round goby in
      the South, provides the basis for the assumption that different diets may lead to
      differences in severity of EMS between different stocks. Lake trout eggs of 18
      females were collected and fertilized individually with the sperm of several
      males. The eggs, eyed embryos and newly-hatched alevins were sampled to examine
      thiamine utilization during embryogenesis. Progenies of females with low (< 0.73
      nmol/g) and high (> 0.85 nmol/g) levels of thiamine were chosen for histological
      studies. The obtained results showed that total thiamine levels in the body and
      yolk of eyed embryos and alevins at hatching were influenced by thiamine levels
      of unfertilized eggs and it decreased during embryogenesis (to 51% in eyed
      embryos and 28% in newly-hatched alevins in comparison to unfertilized eggs). The
      survival of lake trout until hatching stage does not correlate with the thiamine
      level, however it was affected by collection site and was significantly higher in
      fish from the South site (Julian's Reef). At the hatching stage, no pathological
      changes were observed in the brain, olfactory lobe, retina or liver in embryos
      regardless of thiamine concentrations in unfertilized eggs. It has been concluded
      that an enhanced thiamine requirement for the fast muscle mass growth near the
      swim-up stage is responsible for overt and histopathological signs of EMS.
      Current study confirms earlier findings that lake trout suffering from EMS can be
      successfully treated by immersion in thiamine solution as late as at the swim-up
      stage.

PMID- 19576292
TI  - SoFoCles: feature filtering for microarray classification based on gene ontology.
AB  - Marker gene selection has been an important research topic in the classification
      analysis of gene expression data. Current methods try to reduce the "curse of
      dimensionality" by using statistical intra-feature set calculations, or
      classifiers that are based on the given dataset. In this paper, we present
      SoFoCles, an interactive tool that enables semantic feature filtering in
      microarray classification problems with the use of external, well-defined
      knowledge retrieved from the Gene Ontology. The notion of semantic similarity is
      used to derive genes that are involved in the same biological path during the
      microarray experiment, by enriching a feature set that has been initially
      produced with legacy methods. Among its other functionalities, SoFoCles offers a
      large repository of semantic similarity methods that are used in order to derive
      feature sets and marker genes. The structure and functionality of the tool are
      discussed in detail, as well as its ability to improve classification accuracy.
      Through experimental evaluation, SoFoCles is shown to outperform other
      classification schemes in terms of classification accuracy in two real datasets
      using different semantic similarity computation approaches.

PMID- 19576293
TI  - Specific p38 inhibition in stimulated endothelial cells: a possible new anti
      inflammatory strategy after hypothermia and rewarming.
AB  - To protect immature organ systems during corrective cardiac surgery, patients are
      cooled to a minimal temperature of 17 degrees C during cardiopulmonary bypass
      (CPB). However hypothermic CPB triggers the whole body inflammatory response and
      results in unwanted prolonged inflammation. The present study was designed to
      clarify the hypothermia and rewarming induced mechanisms and examine
      interventional pharmacological strategies that could prevent prolonged
      inflammation. Stimulated primary human umbilical vein endothelial cells (HUVECs)
      were exposed to a dynamic temperature protocol analogous to clinical settings.
      Furthermore endothelial cells were pretreated with methylprednisolone and/or
      tacrolimus as well as with MAPK inhibitors (SB203580, U0126 and SP600125). Cell
      viability, expression of IL-6 and ERK 1/2, p38 and SAPK/JNK were investigated.
      Stimulated endothelial cells secreted significantly higher IL-6 protein 2h after
      rewarming in comparison to normothermic control cells. Moreover, dynamic
      temperature changes lead to increased MAPK phosphorylation. Only the combined pre
      treatment with MP and TAC served to inhibit the IL-6 secretion. As intracellular
      signalling pathway we could demonstrate that SB203580 as specific p38 inhibitor
      most effectively down regulated the unwanted IL-6 release after cooling and
      rewarming. Therefore inhibition of p38 or components of the p38 pathway could be
      a promising and selective antiinflammatory therapeutic target after hypothermic
      CPB.

PMID- 19576294
TI  - Grievous disease.

PMID- 19576295
TI  - Tropical or idiopathic chronic pancreatitis: what is in a name?

PMID- 19576296
TI  - Use the Harmless Acute Pancreatitis Score wisely.

PMID- 19576297
TI  - A randomized controlled trial of enemas in combination with oral laxative therapy
      for children with chronic constipation.
AB  - BACKGROUND & AIMS: After 5 years of intensive oral laxative use, up to 30% of
      constipated children still have an unsuccessful outcome. Children refractory to
      oral laxatives might benefit from regular rectal evacuation by enemas. This
      randomized controlled trial compared the effects of additional treatment with
      rectal enemas (intervention) with conventional treatment alone (oral laxatives,
      control) in severely constipated children. METHODS: In a tertiary hospital in the
      Netherlands, 100 children, aged 8-18 years, with functional constipation for at
      least 2 years were randomly assigned to intervention or control groups. The
      control group received education, behavioral strategies, and oral laxatives. The
      intervention group was also given 3 rectal enemas/week, reduced by 1 enema/week
      every 3 months. Outcome measures were defecation and fecal incontinence frequency
      and overall success at 12, 26, 39, and 52 weeks. Overall success was defined as 3
      or more defecations/week and less than 1 fecal incontinence episode/week,
      irrespective of laxative use. RESULTS: Defecation frequency normalized in both
      groups but was significantly higher in the intervention group compared with
      controls at 26 and 52 weeks (5.6 vs 3.9/week, P = .02, and 5.3 vs 3.9/week, P =
      .02, respectively). There were no significant differences between groups in
      reduction of fecal incontinence episodes (P = .49) and overall success rates (P =
      .67). After 1 year of treatment, the overall success rate was 47.1% in the
      intervention group versus 36.1% in the control group. CONCLUSIONS: There is no
      additional effect of enemas compared with oral laxatives alone as maintenance
      therapy for severely constipated children.

PMID- 19576298
TI  - Revisiting the level of evidence in randomized controlled clinical trials: A
      simulation approach.
AB  - BACKGROUND: The Evidence Based Medicine (EBM) paradigm requires that results from
      Randomized Controlled Trials (RCTs) must be assessed for validity before being
      assimilated. However, evaluating available evidence is often still based on
      intuitive processes rather than on rigorous scientific analysis. OBJECTIVE: To
      establish a hierarchy among the different factors influencing the level of
      evidence of RCT results, using a Monte Carlo simulation. METHODS: The complete
      RCT model involved three submodels: i) the input-output submodel for the
      prediction of events (using the sigmoid dose-response relationship as the basic
      model), ii) the execution submodel for deviations from a randomized, controlled
      two-arm parallel trial related to either patient-specific or investigator
      specific elements or both: placebo or nocebo effect, errors of measurement,
      effect of concomitant therapy, regression to the mean phenomenon, blinding
      process, loss to follow-up and randomization process, iii) the covariate
      distribution submodel. RESULTS: The most important factors influencing
      discrepancies in the true-to-observed odds ratio were the blinding process, the
      measurement errors (affecting either the therapeutic or the adverse effects), the
      placebo effect, the effect of concomitant therapies and to a less extent the
      randomization process. Whereas the randomization process remained the only
      relevant factor in double-blinded trials, the hierarchy of other factors was
      modified according to the type of blinding. CONCLUSION: In RCTs, the hierarchy of
      confounding factors differs according to the type of blinding and the current
      short list of components of the strength of evidence (poorly concealed
      randomization and lack of blinding) appears to be incomplete.

PMID- 19576299
TI  - Issues in the design of a randomized noninferiority clinical trial of telemental
      health psychotherapy for rural combat veterans with PTSD.
AB  - This methodological article provides a description of the design, methods, and
      rationale of the first prospective, noninferiority designed randomized clinical
      trial evaluating the clinical and cost implications of delivering an evidence
      based cognitive-behavioral group intervention specifically treating posttraumatic
      stress disorder (PTSD) with a trauma-focused intervention via video
      teleconferencing (VTC). PTSD is a prevalent mental health problem found among
      returning Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) military
      populations. These returning military personnel often live in rural areas and
      therefore have limited access to care and specialized psychological treatments.
      In the field of mental health, telemental health (TMH) technology has introduced
      a potential solution to the persistent problem of access to care in remote areas.
      This study is enrolling approximately 126 returning veterans with current combat
      related PTSD who are receiving services through the Veteran Administration (VA)
      mental health care clinics on 4 Hawaiian Islands. Cognitive Processing Therapy
      (CPT), an empirically supported manualized treatment for PTSD, is being delivered
      across 9 cohorts. Participants are assigned to either the experimental VTC
      condition or the in-person control condition. Assessments measuring clinical,
      process, and cost outcomes are being conducted at baseline, mid-treatment, post
      treatment, and 3 and 6 months post-treatment. The study employs a noninferiority
      design to determine if the group treatment delivered via VTC is as good as the
      traditional in-person modality. In addition, a cost analysis will be performed in
      order to compare the cost of the 2 modalities. Novel aspects of this trial and
      specific challenges are discussed.

PMID- 19576300
TI  - Age-related changes in total and regional fat distribution.
AB  - Aging is associated with progressive changes in total and regional fat
      distribution that have negative health consequences. Indeed, a preferential
      increase in abdominal fat, in particular visceral fat, combined with a decrease
      in lower body subcutaneous fat are commonly cited in the literature. These age
      related changes in body composition can occur independent of changes in total
      adiposity, body weight or waist circumference, and represent a phenotype closely
      associated with increased morbidity and mortality risk. Tissues such as the
      heart, liver and skeletal muscle in the elderly have increased fat deposition,
      which increases risk for insulin resistance and cardiovascular disease.
      Furthermore, aging is associated with increased fat content within bone marrow,
      which exposes the elderly to fracture risk beyond that associated with low bone
      mineral density alone. Many of the age-associated body compositional changes
      cannot be detected by simple anthropometric measures alone, and the influence of
      gender, race or ethnicity, and physical activity patterns on these changes is
      unclear. This review will explore some of these age-related changes in total and
      regional fat distribution. Consideration will also be given to the strengths and
      limitations associated with some of the anthropometric methodologies employed for
      assessing these changes.

PMID- 19576302
TI  - 4.5 Mb microdeletion in chromosome band 2q33.1 associated with learning
      disability and cleft palate.
AB  - We report a 4.5 Mb deletion of 2q33.1 in an individual with developmental delay
      and cleft palate. There have been various previous reports of deletions of 2q3,
      all with varying breakpoints and all larger than the current case. Whilst there
      is some variation in the phenotypes of patients with 2q3 deletions all share a
      commonly deleted region within 2q33.1 which includes SATB2, a gene previously
      shown to be associated with cleft palate. The phenotypic features of our patient
      are milder than those reported so far.

PMID- 19576303
TI  - De novo 9 Mb deletion of 6q23.2q24.1 disrupting the gene EYA4 in a patient with
      sensorineural hearing loss, cardiac malformation, and mental retardation.
AB  - We report on a patient carrying a de novo interstitial deletion of chromosomal
      region 6q23.2-24.1. Interstitial deletions of 6q are rarely reported in the
      literature. Indeed, only four patients with interstitial deletions overlapping
      partially with the deleted region in our patient are described in the literature.
      The aberration was detected by GTG-banding. The size of the deletion was further
      refined by array-CGH and subsequently fine mapped by quantitative real-time PCR.
      The exact size of the deletion and the sequence composition of the breakpoints
      were determined by breakpoint spanning PCR and subsequent sequencing. The patient
      presented with microcephaly, short stature, patent ductus arteriosus,
      sensorineural hearing loss, mental retardation, reduced speech development, and
      abnormal behaviour. The deletion disrupts the gene EYA4. Mutations within this
      gene are associated with postlingual sensorineural hearing loss. The sequencing
      of the breakpoint indicated non homologous end joining as the most likely
      mechanism leading to the rearrangement.

PMID- 19576301
TI  - Processivity factor of DNA polymerase and its expanding role in normal and
      translesion DNA synthesis.
AB  - Clamp protein or clamp, initially identified as the processivity factor of the
      replicative DNA polymerase, is indispensable for the timely and faithful
      replication of DNA genome. Clamp encircles duplex DNA and physically interacts
      with DNA polymerase. Clamps from different organisms share remarkable
      similarities in both structure and function. Loading of clamp onto DNA requires
      the activity of clamp loader. Although all clamp loaders act by converting the
      chemical energy derived from ATP hydrolysis to mechanical force, intriguing
      differences exist in the mechanistic details of clamp loading. The structure and
      function of clamp in normal and translesion DNA synthesis has been subjected to
      extensive investigations. This review summarizes the current understanding of
      clamps from three kingdoms of life and the mechanism of loading by their cognate
      clamp loaders. We also discuss the recent findings on the interactions between
      clamp and DNA, as well as between clamp and DNA polymerase (both the replicative
      and specialized DNA polymerases). Lastly the role of clamp in modulating
      polymerase exchange is discussed in the context of translesion DNA synthesis.

PMID- 19576304
TI  - An interstitial deletion of 7.1Mb in chromosome band 6p22.3 associated with
      developmental delay and dysmorphic features including heart defects, short neck,
      and eye abnormalities.
AB  - Seven cases with an interstitial deletion of the short arm of chromosome 6
      involving the 6p22 region have previously been reported. The clinical phenotype
      of these cases includes developmental delay, brain-, heart-, and kidney defects,
      eye abnormalities, short neck, craniofacial malformations, hypotonia, as well as
      clinodactyly or syndactyly. Here, we report a patient with a 7.1Mb interstitial
      deletion of chromosome band 6p22.3, detected by genome-wide screening array CGH.
      The patient is a 4-year-old girl with developmental delay and dysmorphic features
      including eye abnormalities, short neck, and a ventricular septum defect. The
      deleted region at 6p22.3 in our patient overlaps with six out of the seven
      previously reported cases with a 6p22-24 interstitial deletion. This enabled us
      to further narrow down the critical region for the 6p22 deletion phenotype to
      2.2Mb. Twelve genes are mapped to the overlapping deleted region, among them the
      gene encoding the ataxin-1 protein, the ATXN1 gene. Mice with homozygous
      deletions in ATXN1 are phenotypically normal but show cognitive delay.
      Haploinsufficiency of ATXN1 may therefore contribute to the learning difficulties
      observed in the patients harboring a 6p22 deletion.

PMID- 19576305
TI  - Selection of TNF-alpha binding affibody molecules using a beta-lactamase protein
      fragment complementation assay.
AB  - Protein fragment complementation assays (PCAs) based on different reporter
      proteins have been described as powerful tools for monitoring dynamic protein
      protein interactions in living cells. The present study describes the
      construction of a PCA system based on genetic splitting of TEM-1 beta-lactamase
      for the selection of proteins specifically interacting in the periplasm of
      Escherichia coli bacterial cells, and its application for the selection of
      affibody molecules binding human tumour necrosis factor-alpha (TNF-alpha) from a
      combinatorial library. Vectors encoding individual members of a naive 10(9)
      affibody protein library fused to a C-terminal fragment of the beta-lactamase
      reporter were distributed via phage infection to a culture of cells harbouring a
      common construct encoding a fusion protein between a non-membrane anchored
      version of a human TNF-alpha target and the N-terminal segment of the reporter.
      An initial binding analysis of 29 library variants derived from surviving
      colonies using selection plates containing ampicillin and in some cases also the
      beta-lactamase inhibitor tazobactam, indicated a stringent selection for target
      binding variants. Subsequent analyses showed that the binding affinities (K(D))
      for three selected variants studied in more detail were in the range 14-27 nm.
      The selectivity in binding to TNF-alpha for these variants was further
      demonstrated in both a cross-target PCA-based challenge and the specific
      detection of a low nm concentration of TNF-alpha spiked into a complex cell
      lysate sample. Further, in a biosensor-based competition assay, the binding to
      TNF-alpha of three investigated affibody variants could be completely blocked by
      premixing the target with the therapeutic monoclonal antibody adalimumab
      (Humira), indicating overlapping epitopes between the two classes of reagents.
      The data indicate that beta-lactamase PCA is a promising methodology for
      stringent selection of binders from complex naive libraries to yield high
      affinity reagents with selective target binding characteristics.

PMID- 19576306
TI  - A Jurkat transcriptional reporter cell line for high-throughput analysis of the
      nuclear factor-kappaB signaling pathway.
AB  - The transcription factor, Nuclear Factor-kappaB (NF-kappaB), regulates many genes
      involved in host immunity and cell survival. Unregulated NF-kappaB activity has
      been linked to many chronic inflammatory diseases and is an important target for
      the identification of inhibitors to better manage these disorders. We present a
      novel screening system to identify NF-kappaB inhibitors that combines sensitive
      fluorescence detection with medium- to high-throughput flow cytometry (HyperCyt).
      To validate this approach, we quantified the activation of NF-kappaB by standard
      flow cytometry and the HyperCyt platform. Results were comparable with regard to
      EC(50) values for TNFalpha-mediated activation; however, the HyperCyt platform
      provided more sensitive signal detection and a greater linear range for
      detection. To demonstrate the usefulness of this screening tool, we identified a
      novel inhibitor of NF-kappaB activation from a resveratrol-based chemical
      library. The inhibition of NF-kappaB activation by analog 6q (IC(50) = 19 microm)
      showed a 3.7-fold improvement over that of resveratrol (IC(50) approximately 70
      microm).

PMID- 19576307
TI  - Characterization of 4-alpha-glucanotransferase from Synechocystis sp. PCC 6803
      and its application to various corn starches.
AB  - A putative 4-alpha-glucanotransferase (alphaGTase) gene from Synechocystis sp.
      PCC 6803 was identified being composed of 1505 nucleotides, and the overexpressed
      protein was purified with an affinity chromatography. The recombinant alphaGTase
      had about 57kDa of molecular mass when judged by SDS-PAGE analysis. The optimum
      reaction condition of the alphaGTase was shown to be pH 7 at 45 degrees C in 50mm
      phosphate buffer. This enzyme displayed transglycosylating activity on various
      maltooligosaccharides, of which the smallest donor and acceptor molecules were
      determined to be maltose and glucose, respectively. Various corn starches
      consisting of different proportions of amylopectin and amylose were incubated
      with the recombinant alphaGTase. The change in molecular weight distribution of
      alphaGTase-modified starch was analyzed by HPSEC. The reaction pattern of
      alphaGTase showed substantial decrease in amylopectin and increase in the peak
      corresponding to cycloamylose (CA). The production yield of CA tended to increase
      from 5 to 30% along with the increase in the apparent amylose content in corn
      starch, which suggested that linear amylose chain would be preferred to produce
      CA in the alphaGTase treatment. The detectable minimum degree of polymerization
      (DP) of CA was shown to be 22 by MALDI-TOF-MS analysis. As another action mode of
      alphaGTase, the rearrangement of amylopectin branch-chain distribution occurred
      without hydrolysis to small oligosaccharides. After isoamylolysis, alphaGTase
      treated starch displayed the increase in DP 4-9 and longer than DP 21 when the
      relative proportion of branch chains in amylopectin was determined by HPAEC.

PMID- 19576308
TI  - Youth Conference on European Life Science Careers - creating a promising future.

PMID- 19576309
TI  - Constrained tibial vibration does not produce an anabolic bone response in adult
      mice.
AB  - Osteoporosis is characterized by low bone mass and increased fracture risk. High
      frequency, low-amplitude whole-body vibration (WBV) has been proposed as a
      treatment for osteoporosis because it can stimulate new bone formation and
      prevent trabecular bone loss. We developed constrained tibial vibration (CTV) as
      a method for controlled vibrational loading of the lower leg of a mouse. We first
      subjected mice to five weeks of daily CTV loading (0.5 G maximum acceleration)
      with loading parameters chosen to independently investigate the effects of strain
      magnitude, loading frequency, and cyclic acceleration on the adaptive response to
      vibration. We hypothesized that mice subjected to the highest magnitude of
      dynamic strain would have the largest bone formation response. We observed a
      slight, local benefit of CTV loading on trabecular bone, as BV/TV was 5.2% higher
      in the loaded vs. non-loaded tibia of mice loaded with the highest bone strain
      magnitude. However, despite these positive differences, we observed significantly
      lower measures of trabecular structure in both loaded and non-loaded tibias from
      CTV loaded mice compared to Sham and Baseline Control animals, indicating a
      negative systemic effect of CTV on trabecular bone. Based on this evidence, we
      conducted a follow-up study wherein mice were subjected to CTV or sham loading,
      and tibias were scanned at the beginning and end of the study period using in
      vivo microCT. Consistent with the findings of the first study, trabecular BV/TV
      in both tibias of CTV loaded and Sham mice was, on average, 36% and 31% lower on
      day 36 than day 0, respectively, compared to 20% lower in Age-Matched Controls
      over the same time period. Contrary to the first study, there were no differences
      between loaded and non-loaded tibias in CTV loaded mice, providing no evidence
      for a local benefit of CTV. In summary, 5 weeks of daily CTV loading of mice was,
      at best, weakly anabolic for trabecular bone in the proximal tibia, while daily
      handling and exposure to anesthesia was associated with significant loss of
      trabecular and cortical bone. We conclude that direct vibrational loading of bone
      in anesthetized, adult mice is not anabolic.

PMID- 19576310
TI  - Anatomic variations of the lacunar-canalicular system influence solute transport
      in bone.
AB  - Solute transport in the lacunar-canalicular system (LCS) is essential for bone
      metabolism and mechanotransduction. Using the technique of fluorescence recovery
      after photobleaching (FRAP) we have been quantifying solute transport in the LCS
      of murine long bone as a function of loading parameters and molecular size.
      However, the influence of LCS anatomy, which varies among animal species, bone
      type and location, age and health condition, is not well understood. In this
      study, we developed a mathematical model to simulate solute convection in the LCS
      during a FRAP experiment under a physiological cyclic flow. We found that the
      transport rate (the reciprocal time constant for refilling the photobleached
      lacuna) increased linearly with canalicular number and decreased with canalicular
      length for both diffusion and convection. As a result, the transport enhancement
      of convection over diffusion was much less sensitive to the variations associated
      with chick, mouse, rabbit, bovine, dog, horse, and human LCS anatomy, when
      compared with the rates of diffusion or convection alone. Canalicular density did
      not affect transport enhancement, while solute size and the lacunar density had
      more complicated, non-linear effects. This parametric study suggests that solute
      transport could be altered by varying LCS parameters, and that the anatomical
      details of the LCS need systemic examination to further understand the etiology
      of aged and osteoporotic bones.

PMID- 19576311
TI  - Impact of optimal medical therapy with or without percutaneous coronary
      intervention on long-term cardiovascular end points in patients with stable
      coronary artery disease (from the COURAGE Trial).
AB  - The main results of the Clinical Outcomes Utilizing Revascularization and
      Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in
      the primary end point of all-cause mortality or nonfatal myocardial infarction
      [MI] or major secondary end points (composites of death/MI/stroke;
      hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year
      follow-up in 2,287 patients with stable coronary artery disease randomized to
      optimal medical therapy (OMT) with or without percutaneous coronary intervention
      (PCI). We sought to assess the impact of PCI when added to OMT on major
      prespecified tertiary cardiovascular outcomes (time to first event), namely
      cardiac death and composites of cardiac death/MI, cardiac
      death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac
      death/MI/ACS/stroke, during study follow-up. There were no significant
      differences between treatment arms for the composite of cardiac death or MI (15%
      in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence
      interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite
      cardiovascular events during long-term follow-up, even after excluding
      periprocedural MI as an outcome of interest. Overall, cause-specific
      cardiovascular outcomes paralleled closely the primary and secondary composite
      outcomes of the trial as a whole. In conclusion, compared with an initial
      management strategy of OMT alone, addition of PCI did not decrease the incidence
      of major cardiovascular outcomes including cardiac death or the composite of
      cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.

PMID- 19576312
TI  - Rate of acute ST-elevation myocardial infarction in the United States from 1988
      to 2004 (from the Nationwide Inpatient Sample).
AB  - Advances in the management of atherosclerosis risk factors have been dramatic in
      the previous 10 years. The goal of this study was to evaluate any decrease in age
      adjusted incidence of acute ST-elevation myocardial infarction (STEMI) in a very
      large database of inpatient admissions from 1988 to 2004. The Nationwide
      Inpatient Sample database was used to calculate the age-adjusted rate for STEMI
      from 1988 to 2004 retrospectively. Specific International Classification of
      Diseases, Ninth Revision, codes for MIs consistent with STEMI were used. Patient
      demographic data were also analyzed and adjusted for age. The Nationwide
      Inpatient Sample database contained 1,352,574 patients >40 years of age who had a
      diagnosis of STEMI from 1988 to 2004. Mean age for these patients was 66.06 +/-
      13.69 years. Men had almost 2 times the age-adjusted STEMI rate as women (men
      62.4%, women 37.6%). From 1988 the age-adjusted rate for all acute STEMIs
      remained steady for 8 years (108.3 per 100,000, 95% confidence interval [CI] 99.0
      to 117.5, in 1988 and 102.5 per 100,000, 95% CI 94.7 to 110.4, in 1996). However,
      from 1996 onward, the age-adjusted incidence of STEMI steadily decreased to 1/2
      the incidence of the previous 8 years (50.0 per 100.000, 95% CI 46.5 to 53.5, by
      2004, p <0.01). This decrease was similar across various races and genders. In
      conclusion, the incidence of STEMI was stable from 1988 to 1996, with a steady
      linear decrease to 1/2 by 2004. The cause of the steady decrease in STEMI rate
      most likely reflects the advancement in management of patients with
      atherosclerosis.

PMID- 19576313
TI  - Frequency of elevated troponin I and diagnosis of acute myocardial infarction.
AB  - This study evaluated the incidence and type of acute myocardial infarction (AMI)
      in a consecutive population with increased troponin I (TnI). AMI has recently
      been redefined and subclassified. Incidence, demographic data, angiographic
      findings, and hospital mortality of patients with various AMI subtypes or an
      increased TnI in the absence of AMI have not been previously reported in a
      prospective study. Over a 3-month period, all patients admitted from an emergency
      room or from in-patient services with >1 TnI level >0.04 ng/ml were evaluated and
      subclassified in AMI subgroups. In-hospital or recent coronary angiograms were
      reviewed. In-hospital mortality was noted. Of 2,944 patients with serial TnI
      measurements, 728 had an increased TnI and 701 (23.8%) were evaluated. Two
      hundred sixteen (30.8% with increased TnI and 42.7% with "rule-out MI" on
      admission) met criteria for AMI. One hundred forty-three (20.4%) had type 1, 64
      (9.1%) had type 2, whereas 461 (65.8%) did not meet criteria for AMI. On
      multivariate analysis, use of angiography, peak TnI level, hyperlipidemia, and
      illicit drug use were independently associated with the diagnosis of AMI. TnI of
      0.28 ng/ml had a 70% sensitivity and specificity for AMI diagnosis. In
      conclusion, a minority admitted with increased TnI have AMI by the universal
      definition. Type 1 is the most common AMI and is associated with higher TnI
      values and these patients are more likely to undergo angiography. Type 2 AMI is
      often associated with illicit drug use.

PMID- 19576314
TI  - Safety of contrast in stress echocardiography in stable patients and in patients
      with suspected acute coronary syndrome but negative 12-hour troponin.
AB  - Limited studies are available demonstrating the safety of contrast agents in
      patients undergoing stress echocardiography and none in patients with suspected
      acute coronary syndrome (ACS). Therefore, we sought to assess the safety profile
      of contrast agents in patients with stable chest pain and in those with suspected
      ACS (nondiagnostic electrocardiogram and negative initial 12-hour cardiac
      troponin test results). During a 4-year period, 3,704 patients underwent stress
      echocardiography (exercise or dobutamine), of whom, 929 (25%) had suspected ACS.
      Contrast agents (SonoVue 46%, Luminity 54%) were used in 1,150 patients (31%). No
      patients died with or without contrast administration. No nonfatal acute
      myocardial infarction occurred in patients administered contrast agents compared
      with 3 cases of acute myocardial infarction in the noncontrast group (p = 0.24).
      Two cases of sustained ventricular tachycardia developed, one in each group (p =
      0.98). Compared with those who did not receive contrast, patients in both the
      stable chest pain and the suspected ACS groups had a greater burden of
      cardiovascular risk factors. The left ventricular function at rest was
      significantly worse in the patients who received contrast than in those who did
      not in the suspected ACS group. Also, a greater ischemic burden was present in
      those receiving contrast than in those not receiving it in both the stable chest
      pain and the suspected ACS groups. In conclusion, despite the presence of greater
      risk features compared with patients undergoing unenhanced stress
      echocardiography, the administration of ultrasound contrast agents (SonoVue and
      Luminity) in those with stable chest pain and those with suspected ACS was not
      associated with excess adverse events.

PMID- 19576315
TI  - Usefulness of left ventricular dyssynchrony after acute myocardial infarction,
      assessed by a tagging magnetic resonance image derived metric, as a determinant
      of ventricular remodeling.
AB  - Development of left ventricular (LV) remodeling after acute myocardial infarction
      (AMI) is a serious medical complication. We investigated the correlation of LV
      dyssynchrony after AMI with LV remodeling using magnetic resonance-myocardial
      tagging (MR-MT) derived dyssynchrony index (circumferential uniformity ratio
      estimate [CURE]). Forty-three patients diagnosed with ST-elevation AMI were
      analyzed. After treatment with primary percutaneous intervention, cardiac
      magnetic resonance imaging was performed to obtain a cine image, a delayed
      enhancement image, and an MR-MT image. CURE as a dyssynchrony index was
      calculated from the MR-MT image using HARP software (CURE 0 to 1 = dyssynchrony
      to synchrony). After 6 months, follow-up cardiac magnetic resonance imaging was
      performed to assess degree of LV remodeling. Sixteen patients (37%) had an
      increased LV end-systolic volume (ESV) >15% compared with baseline. The baseline
      LV dyssynchrony index, CURE, was significantly associated with ESV at 6 months (r
      = -0.49, p <0.001) and weakly correlated with change in ESV (percentage) compared
      with baseline values (r = -0.26, p = 0.08). Multivariate analysis showed that
      CURE was associated only with change in ESV (beta -0.39, p = 0.03). Subgroup
      analysis for patients with nonviable myocardium (infarct thickness >75%, n = 31)
      showed that this correlation was stronger (beta -0.52, p = 0.006), suggesting
      that CURE could predict progression of LV remodeling in patients with AMI and
      nonviable myocardium. LV dyssynchrony immediately after AMI is an important
      determinant of LV remodeling. In conclusion, the MR-MT dyssynchrony index, CURE,
      might be useful for prediction of LV remodeling in patients with AMI.

PMID- 19576316
TI  - Cardiogenic shock without flow-limiting angiographic coronary artery disease:
      (from the Should We Emergently Revascularize Occluded Coronary Arteries for
      Cardiogenic Shock Trial and Registry).
AB  - Myocardial infarction often develops when thrombosis occurs at lesions that have
      not previously been flow limiting. However, the development of cardiogenic shock
      complicating acute myocardial infarction in such circumstances has received
      little attention. The characteristics of 15 patients with cardiogenic shock who
      had no flow-limiting angiographic stenoses were compared with those of 767
      patients with > or =1 stenosis who were enrolled in the Should We Emergently
      Revascularize Occluded Coronary Arteries for Cardiogenic Shock (SHOCK) trial and
      registry. Compared with patients with > or =1 flow-limiting stenosis, patients
      with no flow-limiting stenoses were less likely to have pulmonary edema on chest
      x-ray (29% vs 62%, p = 0.008) and to be white (53% vs 82%, p = 0.011), and they
      had lower median highest creatine kinase levels (702 vs 2,731 U/L, p = 0.018).
      For SHOCK trial patients, 1-year survival was 49% for patients with > or =1 flow
      limiting stenosis and 71% for those with no flow-limiting stenoses (p = 0.268).
      In conclusion, patients with cardiogenic shock without flow-limiting stenosis
      have different characteristics, and potentially disease mechanisms, and they do
      not require revascularization.

PMID- 19576317
TI  - Safety and efficacy of achieving very low low-density lipoprotein cholesterol
      levels with rosuvastatin 40 mg daily (from the ASTEROID Study).
AB  - Clinical trial evidence supports the use of intensive statin therapy for patients
      with coronary artery disease. High doses of potent statins have shown the
      greatest clinical benefit, but concerns persist regarding the efficacy and safety
      of achieving very low levels of low-density lipoprotein (LDL) cholesterol. We
      grouped patients treated with 40 mg of rosuvastatin daily by the LDL cholesterol
      achieved according to previous work (<40, 40 to <60, 60 to <80, 80 to <100, and >
      or =100 mg/dl) and by National Cholesterol Education Program targets (<70, 70 to
      <100, and > or =100 mg/dl) in A Study to Evaluate the Effect of Rosuvastatin on
      Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID). The rates
      of key safety end points, including death, hemorrhagic stroke, and liver and
      muscle enzyme elevations, and key efficacy end points (atheroma burden) were
      compared using chi-square testing or Fisher's exact testing. The analysis
      included 471 patients who had had their LDL cholesterol measured at 3 months, of
      whom 340 (72.2%) had LDL cholesterol of <70 mg/dl, exhibiting excellent
      achievement of even the most stringent guideline-based goals. Of these 471
      subjects, 192 (40.8%) had LDL cholesterol > or =40 mg/dl but <60 mg/dl, and 57
      (12.1%) had LDL cholesterol <40 mg/dl. Adverse events occurred infrequently
      during the trial, and no pattern appeared relating the frequency of any adverse
      event to the achieved LDL cholesterol. Similarly, the on-treatment atheroma
      volume, change in atheroma volume, and high percentage of subjects with atheroma
      regression did not differ by the achieved LDL cholesterol. In conclusion,
      although the power to detect such changes was limited, these data showed no clear
      relation between the LDL cholesterol achieved by intensive statin therapy with
      rosuvastatin and adverse effects. Atheroma regression occurred in most patients
      and was not linked to the LDL cholesterol achieved.

PMID- 19576318
TI  - Timing and duration of myocardial ischemia on Holter monitoring following
      percutaneous coronary intervention and their association with clinical outcomes
      (a PROTECT-TIMI 30 Substudy Analysis).
AB  - In patients with unstable angina, evidence of myocardial ischemia on Holter
      monitoring is associated with an adverse prognosis. However, the association of
      duration and timing of ischemia on Holter monitoring with outcomes after
      percutaneous coronary intervention (PCI) in patients with non-ST-segment
      elevation acute coronary syndromes (NSTEACSs) has not been systematically
      evaluated. PROTECT-TIMI 30 randomized 857 patients with NSTEACSs undergoing PCI
      to eptifibatide plus a heparin product or bivalirudin monotherapy. Patients
      underwent continuous Holter monitoring following PCI, and the association between
      ischemia and clinical outcomes was evaluated retrospectively. Forty-three
      patients (5.0%) had ischemia on Holter after PCI. Any ischemia was associated
      with a significant increase in the incidence of death or myocardial infarction
      (MI) within 48 hours (32.6% vs 6.1%, odds ratio 7.5, 95% confidence interval 3.70
      to 15.10, p <0.001). In patients who developed ischemia, there was a 1.44-fold
      increase in the odds for death or MI for every 30 minutes of ischemia (95%
      confidence interval 1.12 to 1.84, p = 0.004). Duration of ischemic events was
      related to their timing, such that ischemic events that occurred within the first
      4 hours after PCI (median duration 141 minutes, interquartile range 36 to 227.5)
      were significantly longer than events occurring 4 to 24 hours after PCI (median
      duration 32.8 minutes, interquartile range 17.5 to 118, p = 0.041). In
      conclusion, early ischemia after PCI for NSTEACS is of longer duration, and
      longer duration of ischemia recognized by Holter monitoring is associated with an
      increased incidence of death or MI. Holter monitoring may be a useful surrogate
      end point in clinical trials.

PMID- 19576319
TI  - Prognostic value of hemoglobin A1C levels in patients with diabetes mellitus
      undergoing percutaneous coronary intervention with stent implantation.
AB  - The optimal glycosylated hemoglobin (HbA1C) target in diabetic patients is a
      subject of ongoing controversy that may be especially pertinent in diabetic
      patients with coronary artery disease. This study aimed to determine the
      prognostic value of preprocedural HbA1C levels in diabetic patients undergoing
      percutaneous coronary intervention (PCI) with stent implantation. From 2002 to
      2007, a cohort of 952 consecutive diabetic patients underwent PCI with stent
      implantation in our center. We compared patients with a normal preprocedural
      HbA1C (< or = 7%, n = 429) with patients with an increased HbA1C (>7%, n = 523).
      One-year rate of major adverse cardiovascular events (MACEs) including death,
      myocardial infarction, and target vessel revascularization was indexed. Baseline
      characteristics were similar between groups, except for body mass index, which
      was higher in the high HbA1C group (32.2 vs 31.2 kg/m(2), p = 0.03). Patients in
      the high HbA1C group were more likely insulin dependent (45.5% vs 26.3%, p
      <0.001). Rates of MACEs were similar (23.7% vs 20.8%) in the high HbA1C and low
      HbA1C groups (p = 0.45). By multivariate analysis, age, renal failure, clinical
      presentation as myocardial infarction, and history of congestive heart failure
      were independently associated with MACEs. In contrast, HbA1C was not associated
      with patient outcome. In conclusion, this study suggests that HbA1C is not a
      predictor of cardiac events in diabetic patients with advanced coronary artery
      disease. These results could explain, at least in part, recent findings of
      randomized clinical trials that suggest the absence of benefit in macrovascular
      complications of a strict glycemia control.

PMID- 19576320
TI  - Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrel
      resistance after drug-eluting stent implantation in Koreans.
AB  - Clopidogrel is a prodrug that has to be converted to an active metabolite by
      hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation.
      Individual variability of platelet inhibition by clopidogrel suggests a
      possibility for genetic factors having a significant influence on clopidogrel
      responsiveness. In this study, we sought to determine the relation of genetic
      polymorphisms of CYP genes to clopidogrel resistance in Koreans. Four hundred
      fifty patients who underwent successful percutaneous coronary intervention with
      drug-eluting stents were randomly assigned to treatment with dual antiplatelet
      regimen (aspirin plus clopidogrel) or triple antiplatelet regimen (aspirin plus
      clopidogrel plus cilostazol). Clopidogrel resistance using VerifyNow P2Y12 assay
      and genetic analysis were performed in 387 patients. Clopidogrel resistance was
      found in 112 patients (28.9%). In the clopidogrel-responsive group, there was a
      significantly higher proportion of cilostazol use. Because cilostazol showed a
      significant influence on clopidogrel resistance, we examined the association of
      single-nucleotide polymorphisms and clopidogrel resistance in the dual and triple
      antiplatelet therapy groups, respectively. In all subjects, the CYP2C19*3A allele
      was significantly more prevalent in the clopidogrel-resistant group compared with
      the clopidogrel-responsive group. Multiple logistic regression analysis
      demonstrated that CYP2C19*3 is an independent predictor of clopidogrel
      resistance. In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an
      independent risk factor of clopidogrel resistance in Korean subjects with
      coronary artery disease.

PMID- 19576321
TI  - Relation of severe coronary artery narrowing to insulin or thiazolidinedione use
      in patients with type 2 diabetes mellitus (from the Bypass Angioplasty
      Revascularization Investigation 2 Diabetes Study).
AB  - Patients with diabetes continue to die of coronary artery disease (CAD) at rates
      2 to 4 times higher than patients without diabetes, despite advances in treatment
      of cardiovascular disease. The role of glycemic control therapies, independent of
      their glucose-lowering effects, on cardiovascular disease is a recurring
      question. We examined the association of glycemic control therapies with extent
      of CAD as measured by coronary angiogram obtained at baseline in 1,803 subjects
      in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D)
      trial who had type 2 diabetes mellitus, documented moderate to severe CAD, and no
      previous cardiac revascularization procedures. The association between glycemic
      control therapy use recorded at baseline and percent coronary artery stenosis and
      myocardial jeopardy index was analyzed by multiple regression models. Insulin use
      at study entry was associated with 23% fewer highly stenotic lesions (> or =70%)
      (p <0.001) and a significantly lower myocardial jeopardy index compared with
      subjects not on insulin, despite a worse cardiac risk factor profile, more
      unstable angina, and increased inflammatory markers in insulin users. Subjects
      taking thiazolidinediones (TZDs) for > or =6 months had 17% fewer highly stenotic
      lesions (p = 0.02) and significantly lower C-reactive protein, fibrinogen, and
      plasminogen activator inhibitor-1 levels compared with those not taking TZDs. In
      conclusion, this cross-sectional study of patients with type 2 diabetes mellitus
      and CAD showed that treatment with insulin or TZDs was associated with fewer
      highly stenotic lesions, independent of disease duration, glycemic control, and
      other risk factors.

PMID- 19576322
TI  - The American Journal of Cardiology and Journal of Periodontology Editors'
      Consensus: periodontitis and atherosclerotic cardiovascular disease.

PMID- 19576323
TI  - Influence of the metabolic syndrome versus the sum of its individual components
      on left ventricular geometry in young adults (from the Bogalusa Heart Study).
AB  - Current preventive cardiology guidelines strongly recommend identification of
      metabolic syndrome (MS), a constellation of cardiovascular risk factors, in
      clinical practice. These MS risk factors, individually or in a cluster, adversely
      alter left ventricular (LV) geometry. However, it is still unclear whether MS
      predicts risk, above and beyond its individual risk factors, for abnormal LV
      geometry. This aspect was examined in 830 asymptomatic patients (mean age 37
      years, 69% whites, 41% men) as a part of the Bogalusa Heart Study. Patients with
      MS (as defined by the National Cholesterol Education Program Adult Treatment
      Panel III) showed adverse levels of echocardiographic parameters compared with
      patients without MS. With respect to MS components, patients with eccentric
      hypertrophy (EH) or concentric hypertrophy (CH) showed higher values of MS risk
      factors compared with patients with normal geometric pattern but no differences
      were noted between patients with normal and concentric remodeling. Of note,
      patients with concentric remodeling versus EH showed significantly higher
      systolic and diastolic blood pressure and fasting glucose levels. A model
      including only MS strongly predicted risk of EH (odds ratio [OR] 4.16, p <0.0001)
      and CH (OR 13.6, p <0.0001) compared with normal LV geometry. In a model
      including only individual MS risk factors, obesity (EH vs normal OR 14.4, p
      <0.0001), high blood pressure (CH vs normal OR 19.38, p <0.0001), and high
      fasting glucose levels (CH vs normal OR 4.02, p = 0.001) were significant
      predictors of abnormal LV geometry. However, the likelihood ratio test and
      comparisons of C-statistics for models including only individual MS risk factors
      versus models also including the MS variable were not significant. In conclusion,
      MS and its individual risk factors were strongly associated with LV geometry.
      However, MS did not predict risk of abnormal LV geometry independent of its
      individual components.

PMID- 19576324
TI  - Flushing profile of extended-release niacin/laropiprant versus gradually titrated
      niacin extended-release in patients with dyslipidemia with and without ischemic
      cardiovascular disease.
AB  - Niacin has beneficial effects on a patient's lipid and lipoprotein profiles and
      cardiovascular risk, particularly at doses >2 g/day, but is underused due to
      flushing. Laropiprant (LRPT), a selective prostaglandin D(2) receptor-1
      antagonist, decreases flushing associated with extended-release niacin (ERN). We
      compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus
      gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of
      Kos Life Sciences LLC). Patients with dyslipidemia (n = 1,455) were randomized
      1:1 to ERN/LRPT (1 g for 4 weeks advanced to 2 g for 12 weeks) or N-ER (0.5 g for
      4 weeks titrated in 0.5-g increments every 4 weeks to 2 g for the final 4 weeks).
      Aspirin/nonsteroidal anti-inflammatory drugs were allowed to mitigate flushing.
      Flushing severity was assessed using the validated Global Flushing Severity Score
      (GFSS; none 0, mild 1 to 3, moderate 4 to 6, severe 7 to 9, extreme 10). Patients
      on ERN/LRPT, despite more rapid niacin titration, had less flushing than those on
      N-ER, as measured by number of days per week with moderate or greater GFSS across
      the treatment period (p <0.001). More than 2 times as many patients had no
      episodes of moderate, severe, or extreme flushing (GFSS > or =4) with ERN/LRPT
      than with N-ER (47.0% vs 22.0%, respectively) across the treatment period. Fewer
      patients on ERN/LRPT discontinued due to flushing than those on N-ER (7.4% vs
      12.4%, p = 0.002). Other than the decrease in flushing, the safety and
      tolerability profile of ERN/LRPT was similar to that of N-ER. In conclusion,
      improvement in flushing with ERN/LRPT versus gradually titrated N-ER supports a
      rapidly advanced 1-g --> 2-g dosing regimen, allowing patients to start at 1 g
      and quickly reach and tolerate the optimal 2 g dose of ERN.

PMID- 19576325
TI  - Safety and tolerability of dalcetrapib.
AB  - Efficacy and safety data for dalcetrapib (RO4607381/JTT-705) are presented,
      following a report of increased mortality and cardiac events with another
      cholesteryl ester transfer protein inhibitor, torcetrapib, associated with off
      target adverse effects (hypertension and the activation of the renin-angiotensin
      aldosterone system). The efficacy and clinical safety of dalcetrapib 300, 600,
      and 900 mg or placebo were assessed (n = 838) in 4 pooled 4-week phase IIa trials
      (1 monotherapy, n = 193; 3 statin combination, n = 353) and 1 12-week phase IIb
      trial (with pravastatin, n = 292). Nonclinical safety, assessed by the induction
      of aldosterone production and aldosterone synthase (cytochrome P450 11B2)
      messenger ribonucleic acid, was measured in human adrenocarcinoma (H295R) cells
      exposed to dalcetrapib or torcetrapib. Dalcetrapib increased high-density
      lipoprotein cholesterol by up to 36% and apolipoprotein A-I by up to 16%. The
      incidence of adverse events (AEs) was similar between placebo (42%) and
      dalcetrapib 300 mg (50%) and 600 mg (42%), with more events with dalcetrapib 900
      mg (58%) (p <0.05, pooled 4-week studies). Six serious AEs (3 with placebo, 1
      with dalcetrapib 300 mg, and 2 with dalcetrapib 600 mg) were considered
      "unrelated" to treatment. Cardiovascular AEs were similar across treatment
      groups, with no dose-related trends and no clinically relevant changes in blood
      pressure or electrocardiographic results. Findings were similar in the 12-week
      study. In vitro, torcetrapib but not dalcetrapib increased aldosterone production
      and cytochrome P450 11B2 messenger ribonucleic acid levels. In conclusion,
      dalcetrapib alone or in combination with statins was effective at increasing high
      density lipoprotein cholesterol and was well tolerated, without clinically
      relevant changes in blood pressure or cardiovascular AEs and no effects on
      aldosterone production as assessed nonclinically.

PMID- 19576327
TI  - Gender differences of electrophysiological characteristics in focal atrial
      tachycardia.
AB  - Gender differences of supraventricular tachycardias such as atrioventricular
      nodal re-entry, atrioventricular re-entry, and atrial fibrillation have been
      reported. There is little evidence of the effect of gender on focal atrial
      tachycardia (FAT). The study consisted of 298 patients who were referred to this
      institution for radiofrequency catheter ablation of FAT from October 1992 to
      April 2008 and included 156 men (52%) and 142 women (48%). Men were significantly
      older than women (57.9 +/- 18.2 vs 47.2 +/- 19.0 years old, p <0.001). Women had
      more associated arrhythmias (17.0% vs 28.9%, p = 0.01), mostly due to an
      increased incidence of atrioventricular nodal re-entrant tachycardia. Men had
      more cardiovascular co-morbidities (19.9% vs 9.9%, p = 0.02), a mechanism of
      increased automaticity (19.1% vs 8.1%, p = 0.01), and nonparoxysmal tachycardia
      (14.7% vs 4.4%, p = 0.01). No gender differences were noted among FAT number,
      left atrial involvement, shortest tachycardia cycle, success rate of catheter
      ablation, or recurrence rate of FAT. Mean duration of follow-up was 63.2 +/- 47.5
      months. Premenopausal women had a lesser cardiovascular co-morbidity (15.3% vs
      4.3%, p = 0.04) and a greater incidence of a mechanism of increased automaticity
      (13.4% vs 2.9%, p = 0.03). In conclusion, gender differences in
      electrophysiologic characteristics were noted in FAT.

PMID- 19576326
TI  - Relation of multiple inflammatory biomarkers to incident atrial fibrillation.
AB  - Basic and clinical studies have suggested that inflammation predisposes to atrial
      fibrillation (AF). We assessed the association of 12 circulating inflammatory
      biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular
      adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity],
      monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand,
      osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident
      AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD =
      9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women)
      developed incident AF. In the multivariable proportional hazards models, the
      inflammatory biomarker panel was associated with incident AF (p = 0.03). With
      stepwise selection (p <0.01 for entry and retention), log-transformed
      osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95%
      confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial
      infarction or heart failure attenuated the association between osteoprotegerin
      and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p =
      0.09). In conclusion, circulating osteoprotegerin concentration was significantly
      associated with incident AF in our community-based sample, possibly mediated by
      interim cardiovascular events.

PMID- 19576328
TI  - Impact of family hypertension history on exercise-induced cardiac remodeling.
AB  - Left ventricular (LV) hypertrophy is a well-established, but highly variable,
      finding among exercise-trained persons. The causes for the variability in LV
      remodeling in response to exercise training remain incompletely understood. The
      present study sought to determine whether a family history of hypertension is a
      determinant of the cardiac response to exercise training. The cardiac parameters
      in 60 collegiate rowers (30 men/30 women; age 19.8 +/- 1.1 years) with (family
      history positive [FH+], n = 22) and without (family history negative [FH-], n =
      38) a FH of hypertension were studied with echocardiography before and after 90
      days of rowing training. The LV mass increased significantly in both groups.
      However, the LV mass increased significantly more in FH- persons (Delta 17 +/- 5
      g/m(2)) than in FH+ persons (Delta 9 +/- 6 g/m(2), p <0.001) with distinctly
      differently patterns of LV hypertrophy between the 2 groups. FH- athletes
      experienced eccentric LV hypertrophy (relative wall thickness index 0.39 +/- 0.4)
      characterized by LV dilation. In contrast, FH+ athletes developed concentric LV
      hypertrophy (relative wall thickness index 0.44 +/- 0.3; p <0.001) characterized
      by LV wall thickening. Furthermore, the eccentric LV remodeling in FH- athletes
      was associated with a more robust enhancement of LV diastolic function than the
      concentric LV remodeling that occurred in FH+ athletes. In conclusion, these
      findings suggest that patterns of exercise-induced LV remodeling are strongly
      associated with FH history status.

PMID- 19576329
TI  - Age- and gender-related differences in quality of care and outcomes of patients
      hospitalized with heart failure (from OPTIMIZE-HF).
AB  - Previous studies have suggested that female and elderly patients with heart
      failure (HF) are less likely to receive guideline-recommended therapies, but
      these studies have involved select patient populations. We evaluated the
      differences in medical care and patient outcomes by age and gender among a broad
      cohort of hospitalized patients with HF. The Organized Program to Initiate
      Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) is
      a registry and performance-improvement program involving 48,612 patients with HF
      from 259 hospitals. The data were analyzed by gender, age <75 years, and age > or
      =75 years. Appropriate angiotensin-converting enzyme inhibitor/angiotensin
      receptor blocker and beta-blocker use were similar between women and men (p =
      0.244 and p = 0.237, respectively). However, compared with men, fewer women
      received hospital discharge instructions (p <0.001) and the length of stay was
      longer (p <0.001). Risk-adjusted in-hospital and postdischarge mortality were
      similar. All guideline-recommended cardiac medications were prescribed less
      frequently at discharge to eligible patients > or =75 than to those <75 years
      (all p <0.001). Older age was independently associated with in-hospital and
      postdischarge mortality risk increases (76% and 62%, respectively; p <0.001 for
      both). In conclusion, among the OPTIMIZE-HF hospitals, female patients with HF
      generally received similar medical care and had similar risks of adverse clinical
      outcomes compared with male patients. Older patients with HF were less likely to
      receive guideline-recommended therapies and remained at greater risk of adverse
      outcomes.

PMID- 19576330
TI  - Long-term clinical response of cardiac resynchronization after chronic right
      ventricular pacing.
AB  - Chronic right ventricular (RV) pacing might elicit unpredictably deleterious
      effects on left ventricular (LV) function similar to that of native left bundle
      branch block (LBBB). The objective of the present study was to evaluate the
      clinical and echocardiographic response to cardiac resynchronization therapy
      after years of chronic RV pacing. In this prospective observational study of 284
      consecutive patients, cardiac resynchronization therapy was performed in 194
      patients (68%) with a native LBBB and in 90 patients (32%) with a pacing-induced
      LBBB after chronic RV pacing (upgraded group). Echocardiographic and clinical
      parameters were evaluated in both groups at baseline and during 2 years of follow
      up. The clinical response was defined as survival with improvement of > or =1 in
      the New York Heart Association class without heart failure hospitalization.
      Reverse LV remodeling was defined as LV end-systolic volume reduction of > or
      =15%. At baseline, the New York Heart Association class, quality of life, and
      exercise capacity were comparable but the LV ejection fraction was significant
      greater and the LV volumes were significant smaller in the upgraded group.
      Changes with time in the clinical parameters, echocardiographic parameters, and
      clinical response were not significantly different between the 2 groups. Reverse
      LV remodeling was observed in 86% in the upgraded group versus 78% of the native
      LBBB group after 1 year (p = 0.39). Survival was not significantly different
      between the 2 groups. In conclusion, comparable clinical and echocardiographic
      improvement was seen when resynchronization therapy was applied in patients with
      preceding chronic RV pacing compared with patients with a native LBBB.

PMID- 19576331
TI  - Osteoporosis treatment and progression of aortic stenosis.
AB  - A decrease in bone mineral density has been reported to be associated with
      increased progression of aortic stenosis (AS). We hypothesized that osteoporosis
      treatment (OT) is associated with decreased progression of AS. We performed an
      observational study of patients with AS from our echocardiographic database
      comparing 18 patients on OT (bisphosphonates, calcitonin, or estrogen receptor
      modulators) with 37 patients not on OT. All patients had serial echocardiograms.
      Patients with mitral stenosis, aortic valve replacement, renal failure, calcium
      disorders, or left ventricular ejection fraction <40% were excluded. Aortic valve
      area (AVA) was calculated using the continuity equation. There was no significant
      difference in age, gender, renal function, hypertension, statin use, diabetes, or
      calcium level between the 2 groups. Mean baseline AVA was 1.33 cm(2) and not
      significantly different between groups. After a mean of 2.4 +/- 1.0 years, mean
      annual changes in AVA were -0.22 +/- 0.22 cm(2) in those not on OT and -0.10 +/-
      0.18 cm(2) in patients receiving OT (p = 0.025). There was a graded association
      between AS progression rate and OT. In a multivariable analysis including age,
      gender, and statin use, only OT was associated with a change in AVA. In
      conclusion, OT is strongly and independently associated with decreased
      progression of AS. This association warrants investigation in a larger,
      prospective study.

PMID- 19576332
TI  - Bone modifiers and the quest to slow progression of aortic stenosis.
AB  - Aortic stenosis (AS) will likely become increasingly frequent with the aging of
      the American population. The difficulties in treating elderly patients with
      critical AS emphasize the potential value of a strategy to slow the advancement
      of aortic valve calcification. Recent prospective trials of statins and
      angiotensin-converting enzyme inhibitors have been disappointing. New options are
      needed to achieve a truly effective strategy for retarding the advancement of AS.
      In this context, the observations of Skolnick et al appearing in this issue of
      The American Journal of Cardiology are particularly intriguing. In a
      retrospective review of patients followed for mild or moderate AS, these
      investigators found that 18 patients receiving treatment for osteoporosis had
      significantly less decrement in aortic valve area on follow-up echocardiography
      than 37 not receiving such treatment. The most attractive explanation is an
      action of drug therapy for osteoporosis, most often bisphosphonates, to retard
      aortic valve calcification. The mechanism for this action is not clear, although
      numerous possibilities can be postulated on the basis of the multiple complex
      processes controlling tissue calcification. In conclusion, the investigators'
      findings deserve further study to clarify drug impact on aortic valve
      calcification as well as confirm the clinical findings in a larger and more
      diverse population. Such investigation should also assess the role of vitamin D
      and calcium supplementation, common features of treatment for osteoporosis.
      Currently available results are too preliminary to justify the use of
      bisphosphonates or other osteoporosis therapies to slow the progression of AS.

PMID- 19576333
TI  - Ventricular arrhythmia following alcohol septal ablation for obstructive
      hypertrophic cardiomyopathy.
AB  - We sought to assess the risk of sudden cardiac death (SCD) and ventricular
      arrhythmia after alcohol septal ablation (ASA) for obstructive hypertrophic
      cardiomyopathy. ASA is a nonsurgical alternative to septal myectomy for treatment
      of symptomatic, drug-refractory, obstructive hypertrophic cardiomyopathy. The
      effect of ASA on ventricular arrhythmia risk is not well established. We examined
      the rates of SCD among 89 patients treated with ASA. The secondary end point was
      ventricular tachycardia/ventricular fibrillation (VT/VF), appropriate implantable
      cardioverter defibrillator (ICD) therapy, or cardiac arrest after ASA among those
      with implanted ICDs or permanent pacemakers (n = 42). Patients were classified as
      either high-risk or low-risk on the basis of established clinical indications for
      ICD implantation. No mortality was attributable to SCD at a mean follow-up of 5.0
      +/- 2.3 years in the entire cohort. Among the 42 patients with an ICD or
      permanent pacemaker, 9 had documented VT/VF, cardiac arrest, or appropriate ICD
      therapy, resulting in an annual event rate of 4.9%/year. The annual event rate
      for VT/VF, cardiac arrest, or appropriate ICD therapy was 2.8%/year (4 of 29
      patients) in low-risk patients and 13.4% in high-risk patients (5 of 13
      patients). A 10-mm Hg increase in the immediate post-ASA gradient was associated
      with a hazard ratio of 2.66 for arrhythmic events (95% confidence interval 1.55
      to 4.56, p <0.001). In conclusion, ASA was performed in patients with highly
      symptomatic, drug-refractory hypertrophic cardiomyopathy with no mortality
      attributable to SCD and an annual rate of VT/VF, cardiac arrest, or appropriate
      ICD therapy of 4.9%/year.

PMID- 19576334
TI  - Prevalence and clinical characteristics of right ventricular dysfunction in
      transient stress cardiomyopathy.
AB  - Transient stress cardiomyopathy (TSC) is a cause of reversible left ventricular
      (LV) dysfunction that is increasingly recognized. Reports to date have focused
      primarily on LV involvement, with little attention paid to associated right
      ventricular (RV) dysfunction. With other forms of LV dysfunction, RV involvement
      has been shown to confer an adverse prognosis. Prevalence, clinical
      characteristics, and short-term prognosis of RV dysfunction in TSC remain ill
      defined. Presenting echocardiograms of 40 patients with TSC were reviewed. RV
      function was assessed by evaluating regional wall motion and calculating a wall
      motion score index (WMSI). RV dysfunction was defined as a WMSI >1.0. Clinical
      and demographic characteristics of patients with and without RV dysfunction were
      compared. RV dysfunction was identified in 27% of patients (11 of 40). RV WMSI
      was 1.20 +/- 0.30 for the entire cohort compared with 1.72 +/- 0.30 for those
      with RV dysfunction (p <0.05). In each case with RV dysfunction, regional wall
      motion abnormalities involved the apex and spared the base. Patients with RV
      dysfunction had higher B-type natriuretic peptide levels, higher pulmonary artery
      systolic pressures, and longer hospital stays. RV dimensions, clinical
      characteristics, electrocardiographic findings, other biomarkers, and in-hospital
      complications were similar. In conclusion, RV wall motion abnormalities,
      predominantly involving the apex and sparing the base, occur in slightly >1/4 of
      cases of TSC. Although associated with higher B-type natriuretic peptide levels,
      higher pulmonary artery systolic pressures, and longer hospital stays, RV
      dysfunction was not associated with significant differences in short-term cardiac
      morbidity or increased early mortality.

PMID- 19576335
TI  - Plasma N-terminal prohormone brain natriuretic peptide as a marker for
      postoperative cardiac events in high-risk patients undergoing noncardiac surgery.
AB  - This study considered if N-terminal prohormone brain natriuretic peptide (NT
      proBNP) is associated with increased risk for postoperative cardiac events in
      high-risk patients undergoing noncardiac surgery. In addition, this report
      describes how levels of NT-proBNP are affected by noncardiac surgery. The study
      design was a prospective cohort study that enrolled 83 patients age > or =50
      years with > or =1 risk factor for coronary artery disease having intermediate or
      high-risk noncardiac surgery. NT-proBNP levels were measured preoperatively and
      on postoperative days 1 and 3. During the month following surgery, 25 patients
      (33%) had a combined 37 postoperative cardiac events including 15 episodes of
      heart failure (20%), 12 episodes of new dysrhythmia (16%), 7 myocardial
      infarctions (9%), and 3 cardiac arrests (4%). Preoperative NT-proBNP level > or
      =457 pg/ml was significantly associated with occurrence of a postoperative
      cardiac event (odds ratio 10.5, 95% confidence interval 1.9 to 56.6, p = 0.006).
      After surgery, 64 of 72 patients (89%) had an increase in NT-proBNP from their
      preoperative level. In conclusion, this study determined there was a significant
      association between elevated preoperative NT-proBNP and occurrence of a
      postoperative cardiac event. In addition, increased NT-proBNP after noncardiac
      surgery is not uncommon even in the absence of clinically identifiable heart
      failure.

PMID- 19576336
TI  - Meta-analysis of adverse cardiovascular outcomes associated with antecedent
      hypertension after myocardial infarction.
AB  - The aim of this study was to investigate the association of antecedent
      hypertension with adverse cardiovascular outcomes after myocardial infarction. A
      search of Medline and EMBASE was supplemented by manual searches of the
      bibliographies of key retrieved reports. The studies were included if they
      reported antecedent hypertension as a risk factor for adverse outcomes (death,
      stroke, congestive heart failure, recurrent myocardial infarction) in survivors
      of myocardial infarctions. Relative risks (RRs) were pooled using a random
      effects model, and the robustness of the pooled RRs was evaluated in sensitivity
      analyses. Cumulative meta-analysis, by chronologic year of study beginning, was
      also performed. The search yielded 17 studies (n = 56,748 participants) that
      reported antecedent hypertension with adverse outcomes for survivors of
      myocardial infarctions. Randomized clinical trials (n = 8) were pooled separately
      from cohort studies (n = 9). For randomized clinical trials, the pooled RRs were
      1.19 (95% confidence interval [CI] 1.13 to 1.26) for all-cause mortality and 1.29
      (95% CI 1.09 to 1.53) for cardiovascular disease mortality. For cohort studies,
      the pooled RRs were 1.46 (95% CI 1.34 to 1.61) for all-cause mortality and 1.54
      (95% CI 1.22 to 1.93) for cardiovascular disease mortality. Antecedent
      hypertension was also consistently associated with an increased risk for stroke,
      congestive heart failure, and recurrent myocardial infarction. Pooled estimates
      were robust in sensitivity analysis. In conclusion, antecedent hypertension was
      associated with adverse outcomes for survivors of myocardial infarctions, the
      association of antecedent hypertension with all-cause mortality outcomes
      decreased over time, and this decreased association reflects improved treatment
      and management of hypertension in more recent years.

PMID- 19576337
TI  - Relation between inheritance of cyanotic congenital heart disease and persistent
      foramen ovale.
AB  - Cyanotic congenital heart disease (CCHD) usually occurs sporadically, but
      occasionally it is familial without evidence of Mendelian inheritance. The
      investigators previously reported an association between dominant inheritance of
      clinically significant atrial shunts (large persistent foramina ovale and small
      atrial septal defects) and migraine with aura in some families. In 1 family, 4
      patients with CCHD were linked by relatives with atrial shunts. The presence of
      atrial shunts and migraine symptoms was investigated in another family in which 3
      members had CCHD. Contrast echocardiography was used to detect whether atrial
      right-to-left shunts were present in family members. A consultant neurologist,
      who was blinded to cardiac findings, diagnosed and categorized migraine symptoms.
      In this family, relatives with atrial right-to-left shunts linked 3 members who
      had CCHD. There appears to be dominant inheritance of atrial shunts, which is
      linked to inheritance of CCHD in some families. In conclusion, it is possible
      that the gene responsible most often causes an atrial shunt but sometimes causes
      more complex heart disease.

PMID- 19576338
TI  - Usefulness of beta blockers in high-risk patients after myocardial infarction in
      conjunction with captopril and/or valsartan (from the VALsartan In Acute
      Myocardial Infarction [VALIANT] trial).
AB  - Concern has been raised about combining beta blockers with angiotensin-receptor
      blockers in patients with heart failure. The VALsartan In Acute myocardial
      infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction
      complicated by heart failure or documented left ventricular systolic dysfunction.
      These patients were randomly allocated to treatment with valsartan, captopril, or
      both. Physicians were also encouraged to prescribe beta blockers because of
      previous evidence of benefit. The baseline characteristics, treatments, and
      outcomes were compared among 4 groups: patients taking beta blockers at admission
      only, at discharge only, at both admission and discharge, and neither. Patients
      treated with beta blockers were at lower risk than those not treated at any
      period. Those treated with beta blockers at both intervals had a lower 3-year
      mortality rate (17.7%) than those treated only at randomization (30.7%) or only
      at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not
      treated at either point. No statistically significant interaction with prognosis
      was observed between beta-blocker use and treatment with valsartan or valsartan
      plus captopril. Patients discharged with a beta blocker had a significant
      survival advantage after adjustment for differences in baseline characteristics
      and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to
      0.98, p = 0.02). This association was most pronounced in patients prescribed
      consistent beta blockers at randomization and discharge and was present in both
      patients with impaired and those with preserved systolic left ventricular
      function. These results have further confirmed that beta blockers reduce the risk
      of death and nonfatal cardiovascular events in patients with heart failure or
      systolic left ventricular dysfunction after myocardial infarction. In conclusion,
      no evidence was found of adverse interactions between the angiotensin-receptor
      blocker valsartan and beta blockers or of a negative effect of the combination of
      valsartan, captopril, and beta blockers.

PMID- 19576339
TI  - Sudden cardiac death in patients with silent myocardial ischemia after myocardial
      infarction (from the Swiss Interventional Study on Silent Ischemia Type II
      [SWISSI II]).
AB  - The occurrence of sudden cardiac death (SCD) in patients with silent ischemia
      after myocardial infarction (MI) and the factors facilitating SCD are unknown.
      This study aimed to determine the factors facilitating SCD in patients with
      silent ischemia after MI. In the Swiss Interventional Study on Silent Ischemia
      Type II (SWISSI II), 201 patients with silent ischemia after MI were randomized
      to percutaneous coronary intervention (PCI) or medical management. The main end
      point of the present analysis was SCD. Multivariable regression models were used
      to detect potential associations between baseline or follow-up variables and SCD.
      During a mean follow-up of 10.3 +/- 2.6 years, 12 SCDs occurred, corresponding to
      an average annual event rate of 0.6%. On multivariate regression analysis, the
      decline in the left ventricular ejection fraction (LVEF) during follow-up was the
      only independent predictor of SCD (p = 0.011), other than age; however, the
      baseline LVEF was not. The decline in LVEF was greater in patients receiving
      medical management than in those who had received PCI (p <0.001), as well as in
      patients with residual myocardial ischemia or recurrent MI compared with patients
      without these findings (p = 0.038 and p <0.001, respectively). Compared with
      medical management, PCI reduced the rate of residual myocardial ischemia (p
      <0.001) and recurrent MI (p = 0.001) during follow-up. In conclusion, patients
      with silent ischemia after MI are at a substantial risk of SCD. The prevention of
      residual myocardial ischemia and recurrent MI using PCI resulted in better long
      term LVEF and a reduced SCD incidence.

PMID- 19576340
TI  - Clinical significance of borderline elevated troponin I levels across different
      assays in patients with suspected acute coronary syndrome.
AB  - We aimed to elucidate the clinical significance of borderline troponin I (TnI)
      increases and see if such increases are of similar significance across different
      assays. Markedly increased TnI is a strong predictor of adverse cardiac events.
      It is not clear if borderline increases with different commercially available TnI
      assays provide similar prognostic information. From January 2001 to February
      2004, 3 different TnI assays (Beckman Access TnI, Beckman Access AccuTnI, and
      Vitros ECI Troponin) were used to evaluate the peak TnI value in 1,152
      consecutive patients admitted with suspected acute coronary syndrome/non-ST
      elevation myocardial infarction (MI). Recommended cutoffs were used to
      differentiate borderline from marked increases reported as consistent with MI.
      Clinical data and 30-day death/new MIs were determined by chart abstraction.
      Demographics and cardiac risk factors were similar for the 3 groups. Frequency of
      borderline TnI ranged widely among assays (18.7% to 42.1%) but was significantly
      less with the Vitros ECI Troponin assay (p <0.0001). Prognostic significance of
      borderline increased TnI values also varied greatly by assay, with borderline
      Beckman Access AccuTnI increases being predictive of adverse 30-day outcomes
      (odds ratio 4.0, 95% confidence interval 1.46 to 10.97, p = 0.007), but not with
      the other 2 assays. Borderline increases were significantly associated with
      chronic renal insufficiency (CRI; serum creatine >1.5); the relation to adverse
      30-day outcomes and borderline increases persisted after correcting for CRI in a
      multivariate logistic regression model. In conclusion, although borderline
      increased TnI levels are common and significantly associated with CRI, they do
      not all portend the same clinical prognosis. This study highlights the need for
      standardization of TnI levels across different assays.

PMID- 19576341
TI  - Trends in atrial fibrillation complicating acute myocardial infarction.
AB  - Atrial fibrillation (AF) is a common complication of acute myocardial infarction
      (AMI) and this arrhythmia is associated with increased morbidity and mortality in
      patients with AMI. Limited information is available, however, about changing, and
      contemporary, trends in the incidence and death rates associated with AF
      complicating AMI. We examined the magnitude and impact of AF and the risk of
      stroke and hospital and long-term death rates in a population-based study of
      patients hospitalized with AMI. The study population consisted of 7,513 residents
      of the Worcester, Massachusetts, metropolitan area hospitalized with AMI at all
      greater Worcester medical centers during 9 biennial years from 1990 to 2005.
      Overall incidence of AF complicating AMI was 13.3% and rates of AF increased
      during the most recent years under study. Patients who developed AF were at
      greater risk for acute stroke (adjusted odds ratio 2.25, 95% confidence interval
      1.36 to 3.71) and dying during hospitalization (adjusted odds ratio 1.79, 95%
      confidence interval 1.46 to 2.19) compared with patients who did not develop AF
      during hospitalization for AMI. Postdischarge survival was significantly poorer
      in patients who developed AF. Odds of dying after AF did not change appreciably
      over the years under study. In conclusion, results of this study in residents of
      a large New England metropolitan area suggest that AF remains a frequent
      complication of AMI and is associated with a poor prognosis. Increased
      surveillance and targeted therapeutic approaches appear warranted for these high
      risk patients.

PMID- 19576342
TI  - Predictors of early discontinuation of evidence-based medicine after acute
      coronary syndrome.
AB  - Use of evidence-based medicine (EBM) improves outcomes after acute coronary
      syndromes (ACS), yet patients often discontinue prescribed therapies after
      discharge. Although such discontinuation is well documented, patients' reasons
      for medication discontinuation have not been reported. MAINTAIN is a longitudinal
      follow-up registry of CRUSADE/ACTION, which enrolled patients during an ACS
      hospitalization from January 2006 to September 2007. All discharge medications
      were obtained from hospital charts. Patients were interviewed by telephone 3
      months after discharge to determine if EBM classes prescribed at discharge were
      continued (aspirin, clopidogrel, beta blockers, angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, and lipid-lowering medications). If
      discontinuation occurred, patients were asked if it was with provider
      knowledge/input or not (self-discontinuation). A multivariable logistic
      regression model was performed to identify factors associated with self
      discontinuation of prescribed EBM. Of the 1,077 patients interviewed, 1,006
      (93.4%) were discharged on aspirin, 816 (75.8%) on clopidogrel, 982 (91.2%) on
      beta blockers, 745 (69.2%) on angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, and 968 (89.9%) on lipid-lowering
      medications. At 3-month follow-up, 304 patients (28.2%) had discontinued > or =1
      of these prescribed EBM classes. Although many reported provider involvement,
      most discontinuation (61.5%) was self-determined. Factors independently
      associated with self-discontinuation were no pharmacy coinsurance, increasing
      number of medications, not using reminder tools (e.g., pillbox), lower education,
      and dialysis. In conclusion, 1/3 of patients with ACS discontinue > or =1 of
      their prescribed EBMs within 3 months of hospital discharge, and most of this
      discontinuation is without provider involvement. Patient education, better
      prescription drug coverage, and reminder strategies may improve use of EBMs at 3
      months after discharge from ACS admission.

PMID- 19576344
TI  - Utility of the frontal plane QRS axis in identifying non-ST-elevation myocardial
      infarction in patients with poor R-wave progression.
AB  - Poor R-wave progression (PRWP) is a common electrocardiographic phenomenon in
      which the anticipated increase in R-wave amplitude in successive precordial
      leads, V(1) to V(5), fails to occur. PRWP is prevalent in approximately 10% of
      hospitalized adult patients, predominantly in those with coronary artery disease.
      Debate is ongoing on its association with myocardial infarction (MI). However,
      studies that showed no association failed to appraise the significance of the QRS
      axis in relation to PRWP among such patients with MI. In our retrospective study,
      we consecutively identified 150 unselected adult patients with PRWP among 660
      successive admissions to the general medical floors of a tertiary care teaching
      hospital (Saint Vincent Hospital, Worcester, Massachusetts). After excluding
      patients with anterior wall Q-wave MI (defined as the presence of a QS complex or
      Q-wave > or =1 mm deep in V(2) or V(3)), sudden unexpected death, MI after
      percutaneous coronary interventions or coronary artery bypass grafting during
      this hospitalization, Wolff-Parkinson-White syndrome, pacemakers, bundle branch
      blocks, and electrocardiograms that were of poor quality or affected by severe
      motion artifact, inconsistencies with patient identification, or errors in lead
      placement, 137 patients remained. The patients were then screened for non-ST
      segment elevation MI (NSTEMI) during the present admission. The DePace criteria
      for PRWP were systematically used for all patients, and the QRS axis was
      calculated using limb leads based on Einthoven's equilateral triangle (normal was
      considered -30 degrees to 100 degrees ). Of the 137 study patients screened with
      PRWP, 38 had NSTEMI (25.3%). Thirty-one had a normal QRS axis (mean age +/-
      standard deviation 71.3 +/- 12 years), and 7 showed either right or left axis
      deviation (mean age +/- standard deviation 64.3 +/- 15 years). This proved to be
      statistically significant (p <0.0001) within this cohort of NSTEMI patients. In
      conclusion, PRWP determined using the DePace criteria in the presence of a normal
      QRS axis appears to be more significantly associated with the presence of overall
      MI within this cohort of NSTEMI patients.

PMID- 19576345
TI  - Usefulness of combining serum uric acid and C-reactive protein for risk
      stratification of patients with coronary artery disease (Bezafibrate Infarction
      Prevention [BIP] study).
AB  - Combined assessment of serum uric acid (UA) and C-reactive protein (CRP) compared
      with single-marker evaluation in patients with coronary artery disease (CAD) was
      performed. CRP is an independent predictor of cardiac events in patients with or
      without CAD. Data regarding the prognostic value of UA in patients with CAD are
      conflicting. The primary end point (fatal or nonfatal myocardial infarction or
      sudden cardiac death) was related to levels of UA and CRP in 2,966 patients with
      CAD enrolled in the Bezafibrate Infarction Prevention trial who were followed for
      a mean period of 6.2 years. Primary end-point rates were directly related to
      increasing tertiles (from tertile 1 [T1] to tertile 3 [T3]) of UA (12.7%, 12.8%,
      and 17.6% respectively, p for trend <0.0001) and CRP (11.5%, 14.2%, and 17.3%
      respectively, p for trend <0.002). By multivariable analysis, T3 UA (>6.25 mg/dl)
      and T3 CRP (>5.37 mg/dl) were shown to be independently associated with a
      significant increase in risk for the primary end point (hazard ratio 1.30, 1.01
      to 1.68, p = 0.04; hazard ratio 1.31, 1.02 to 1.69, p = 0.03, respectively).
      Primary end-point rates were similarly high in those patients with a combination
      of T3 UA and T1 CRP levels (hazard ratio 1.68, 1.05 to 2.66) or a combination of
      T3 CRP and T1 serum UA levels (hazard ratio 1.64, 1.04 to 2.58) or in patients
      with T3 of the 2 markers (hazard ratio 1.66, 1.07 to 2.59). In conclusion,
      combined assessment of UA and CRP levels provides incremental information for
      risk stratification of patients with CAD with low levels of a single marker.

PMID- 19576343
TI  - Predictors of six-month major adverse cardiac events in 30-day survivors after
      acute myocardial infarction (from the Korea Acute Myocardial Infarction
      Registry).
AB  - Little is known about risk factors for 6-month major adverse cardiac events
      (MACEs) in 30-day survivors after acute myocardial infarction (AMI). We
      investigated predictors of 6-month MACE in 30-day survivors after MI from the
      Korea Acute Myocardial Infarction Registry (KAMIR). From November 2005 to January
      2008, 9,706 patients (6,983 men, mean age 64.0 +/- 12.4 years) who survived >30
      days after AMI were analyzed. The primary end point was 6-month MACEs including
      death, MI, and revascularization. During 6-month follow-up, 317 patients (3.2%)
      had MACEs including 66 (0.6%) deaths, 23 (0.2%) recurrent MIs, and 218 (2.2%)
      revascularizations. In multivariate logistic regression analysis, factors
      reflecting demographics (body mass index), severity of left ventricular systolic
      dysfunction (Killip class >I, in-hospital cardiogenic shock, use of intra-aortic
      balloon pump), residual myocardial ischemia (previous coronary heart disease,
      multivessel disease), and electrical instability (ventricular
      tachycardia/ventricular fibrillation on admission) were independent predictors of
      6-month MACEs after adjustment for clinical, angiographic, and procedural data.
      Plasma level of N-terminal pro-B-type natriuretic peptide provided an additional
      prognostic value predicting 6-month MACEs. In conclusion, this study provides
      useful prognostic information for clinicians to advise patients who have survived
      the acute phase of MI. More intensive management is needed in survivors after MI
      with these high-risk features.

PMID- 19576346
TI  - Relation of bone mineral density to stress test-induced myocardial ischemia.
AB  - Dual-energy x-ray absorptiometric scans of the spine and left hip were performed
      before stress testing for myocardial ischemia in 629 women and 136 men (mean age
      63 years) with chest pain and no previous coronary artery disease. Of the 765
      patients, 254 (33%) had osteoporosis, 260 (34%) had osteopenia, and 251 (33%) had
      normal bone mineral density (BMD). Stress test-induced myocardial ischemia was
      present in 95 of 254 patients (37%) with osteoporosis, in 81 of 260 patients
      (31%) with osteopenia, and in 62 of 251 patients (25%) with normal BMD (p = 0.002
      comparing osteoporosis with normal BMD and p = 0.007 comparing osteoporosis or
      osteopenia with normal BMD). Stepwise logistic regression analysis showed that
      patients with osteoporosis or osteopenia had a 1.7 times higher chance of stress
      test-induced myocardial ischemia than those with normal BMD after controlling the
      confounding effects of systemic hypertension, diabetes mellitus, body mass index,
      and age. In conclusion, patients with chest pain undergoing stress testing have a
      higher prevalence of stress test-induced myocardial ischemia if they have
      osteoporosis or osteopenia than if they have normal BMD.

PMID- 19576348
TI  - Comparison of rapamycin- and paclitaxel-eluting stents in patients undergoing
      primary percutaneous coronary intervention for ST-elevation myocardial
      infarction.
AB  - Compared with bare metal stents, sirolimus- and paclitaxel-eluting stents (SESs
      and PESs, respectively) have been shown to improve angiographic and clinical
      outcomes after percutaneous coronary intervention (PCI) in elective patients and
      those with ST-elevation myocardial infarction (STEMI). The aim of the present
      study was to compare SESs with PESs in patients with STEMI undergoing primary
      PCI. Patients with STEMI were randomized 1:1 to receive SESs (n = 196) or PESs (n
      = 201). The primary end point was late lumen loss at 9-month follow-up by
      quantitative coronary angiography. Secondary end points were major adverse
      cardiac clinical events (death, reinfarction, target vessel revascularization) at
      1 month and 9 and 12 months. Three hundred ninety-seven patients with STEMI were
      randomized. The 2 groups had comparable baseline clinical and angiographic
      characteristics. Mortality was low, 1.5% after 30 days, 2.3% after 9 months, and
      3.1% after 1 year. There was no difference in any clinical outcome at any follow
      up period between the 2 treatment groups. Follow-up angiography was completed in
      272 of 397 patients (69%). Mean +/- SD in-stent late loss was 0.01 +/- 0.42 mm in
      the SES group versus 0.21 +/- 0.50 mm in the PES group (difference -0.20 mm, p =
      0.001). In conclusion, in patients with STEMI, primary PCI with SESs results in
      less late loss compared with PESs. However, these benefits did not translate into
      a significant decrease in major adverse cardiac events at 1-year follow-up.

PMID- 19576347
TI  - Can acute occlusion of the left anterior descending coronary artery produce a
      typical "takotsubo" left ventricular contraction pattern?
AB  - The takotsubo syndrome (TS) takes its name from a distinctive left ventricular
      (LV) contraction abnormality. Patients with this disorder present with clinical
      findings of an acute ischemic event. Despite the absence of obstructive coronary
      artery disease, there is a hallmark LV contraction abnormality, namely
      hypercontractility of the base but akinesia or dyskinesis of the apex. Many
      discount a role for the epicardial coronary arteries in this disorder because the
      LV contraction abnormality appears to overlap >1 vascular territory. To test this
      assumption we analyzed the contraction pattern associated with left anterior
      descending coronary artery (LAD) occlusion. From May to September 2006, 43
      patients underwent primary percutaneous coronary intervention for acute ST
      elevation myocardial infarction due to LAD occlusion. Their left ventriculograms
      were randomly mixed with those of 47 patients clinically labeled as TS. Two
      reviewers unaware of the clinical diagnosis characterized the LV contraction
      pattern of all 90 as typical of TS or not. In 6 of the 43 patients (14%) with
      primary PCI the 2 reviewers considered the pattern to be typical, and in 5 (12%),
      1 of 2 reviewers did. Thus, in 26% >/=1 reviewer believed that the pattern
      associated with LAD occlusion was typical of TS. In conclusion, the
      characteristic TS contraction pattern may be seen in some patients with acute
      occlusion of the LAD. It would be premature to dismiss the possibility of
      transient LAD occlusion as part of the pathogenesis of that disorder.

PMID- 19576349
TI  - Timing, causes, and predictors of death after three years' follow-up in the
      Danish Multicenter Randomized Study of Fibrinolysis versus Primary Angioplasty in
      Acute Myocardial Infarction (DANAMI-2) trial.
AB  - This study evaluated the timing, causes, and predictors of death during long-term
      follow-up after primary angioplasty with stent implantation versus in-hospital
      fibrinolysis with a tissue plasminogen activator (alteplase). We randomized 1,572
      patients with ST-elevation myocardial infarction to primary angioplasty or
      alteplase and followed them for 3 years. The causes of death were prospectively
      assessed by an end point committee unaware of the study treatment. A total of 225
      patients (14.3%) died, 113 within the first 30 days and 112 between 31 days and 3
      years. The mortality and causes of death did not differ between the 2 treatments.
      The causes of death were cardiogenic shock/congestive heart failure (41%), sudden
      death (17%), other cardiac death (10%), cancer (12%), and other noncardiac death
      (20%). Cardiac death was predominant during the first month only (86% of early
      deaths), and noncardiac death and cardiac death were equally frequent after 30
      days (49% and 51% of late deaths, respectively). Independent predictors of death
      after discharge were age, left ventricular ejection fraction, diabetes, Killip
      class, and a lack of treatment with a beta blocker or statin. In conclusion, the
      causes of death did not differ between alteplase treatment and primary
      angioplasty with stent implantation. One half of the deaths within 3 years after
      ST-elevation myocardial infarction occurred during the first 30 days, and cardiac
      death was predominant during the first 30 days only.

PMID- 19576350
TI  - Comparison of outcomes using bare metal versus drug-eluting stents in coronary
      artery disease patients with and without human immunodeficiency virus infection.
AB  - Patients with human immunodeficiency virus (HIV) who undergo percutaneous
      coronary intervention have a substantial risk of subsequent cardiovascular
      events. However, outcome data from HIV-infected patients who receive drug-eluting
      stents (DESs) are limited. We hypothesized that HIV-infected patients treated
      with DESs would have fewer recurrent cardiac events compared with those who
      receive bare metal stents (BMSs). We evaluated 97 HIV-infected patients and 97
      non-HIV control patients who had undergone percutaneous coronary intervention
      between January 2000 and July 2007. Clinical, laboratory, and angiographic data
      were obtained by chart review. Major adverse cardiovascular events (MACE),
      defined as clinically driven coronary revascularization, nonfatal myocardial
      infarction, and cardiovascular death, were adjudicated by 2 independent
      physicians. The mean age of the HIV cohort was 53 years, and all patients were
      men. Compared with non-HIV patients, HIV-infected patients were less likely to
      have hypertension, diabetes mellitus, and previous coronary artery disease and
      were more likely to have been treated with longer stent length and more stents.
      During a mean follow-up of 3.1 years, patients who received a DES had a lower
      rate of MACE compared with those who had received a BMS, regardless of HIV
      status. After multivariate adjustment for baseline characteristic differences,
      non-HIV-DES patients had 65% fewer MACE and HIV-DES patients had 60% fewer MACE
      compared with non-HIV-BMS patients. In conclusion, these data suggest that
      treatment with DESs in the HIV population is safe and efficacious.

PMID- 19576351
TI  - Effect of gradual computerized angioplasty on outcomes of patients undergoing
      coronary stenting.
AB  - Mechanical trauma caused by percutaneous coronary intervention is a major factor
      contributing to subsequent cardiac events, restenosis, and the need for target
      lesion revascularization (TLR). To minimize this trauma, we developed a
      Computerized Angioplasty Pressure Sensor and Inflator Device (CAPSID) for gradual
      inflation. The objective of the present prospective randomized study was to
      examine whether the use of this novel device reduced TLR, as well as cardiac
      events, in patients undergoing stenting. Patients undergoing coronary stenting
      were eligible and randomized to receive CAPSID or standard manual percutaneous
      coronary intervention. In the CAPSID group, slow, gradual balloon inflation was
      performed using a personal computer. Patients with acute ST-elevation myocardial
      infarction or the need for percutaneous coronary intervention for total
      occlusions, left main disease, and vein grafts were excluded. Clinical follow-up
      for major adverse cardiac events, including death, acute myocardial infarction,
      and TLR, was performed at 12 months. A total of 310 patients were enrolled in the
      study. No significant differences were found in the clinical characteristics
      between the CAPSID and control groups. At 1 year of follow-up, the CAPSID group
      had had a significantly lower rate of major adverse cardiac events (8% vs 18%, p
      <0.01) driven by significantly lower rates of acute myocardial infarction (1% vs
      7%, p <0.01) and TLR (5% vs 12%, p <0.05). In conclusion, gradual computerized
      balloon inflation using CAPSID as a platform for angioplasty and stenting
      significantly reduced TLR and major adverse cardiac events at 1 year in patients
      undergoing coronary stenting. The use of this novel device may improve outcomes
      in patients undergoing coronary stenting.

PMID- 19576352
TI  - Assessment, mechanisms, and clinical implication of variability in platelet
      response to aspirin and clopidogrel therapy.
AB  - Antiplatelet therapy is the mainstay of treatment for patients with
      cardiovascular disease. However, some patients experience adverse cardiac events
      despite treatment with single- or dual-antiplatelet (aspirin and clopidogrel)
      therapy. Some of those events could be caused by low responsiveness to aspirin or
      clopidogrel. The frequency of this phenomenon has been reported to range from 1%
      to 45% for the 2 drugs. This wide range arises from the lack of a "gold-standard"
      definition to assess antiplatelet drug response and differences in assays,
      agonist concentrations, and cut-off points. Regardless of the variability in the
      incidence of aspirin or clopidogrel low responsiveness, several studies have
      indicated a clear relation between clopidogrel or aspirin low responsiveness and
      cardiovascular events. The evidence for an association between adverse clinical
      events and the results of ex vivo platelet function tests is stronger for
      clopidogrel than for aspirin. Currently, there is no established therapeutic
      approach for managing low response to aspirin or clopidogrel that has been shown
      in large trials to have clinical benefit. This review focuses on laboratory
      testing of antiplatelet response to aspirin and clopidogrel, the prevalence of
      low response, potential mechanisms, clinical significance, and prognostic value
      of this phenomenon and alternative approaches to optimize treatment in patients
      with low response to the drugs.

PMID- 19576353
TI  - Long-term lipid effects of pioglitazone by baseline anti-hyperglycemia medication
      therapy and statin use from the PROactive experience (PROactive 14).
AB  - Studies have shown that pioglitazone treatment in patients with type 2 diabetes
      mellitus can improve parameters of diabetic dyslipidemia. The aim of this study
      was to examine the effect of pioglitazone on triglycerides, high-density
      lipoprotein cholesterol, and low-density lipoprotein cholesterol levels in
      patients from the Prospective Pioglitazone Clinical Trial in Macrovascular Events
      (PROactive) to determine whether pioglitazone-induced lipid effects were altered
      by different baseline antihyperglycemia medication or statin use. PROactive was a
      long-term, randomized, double-blind, cardiovascular outcomes study in patients
      with type 2 diabetes at high cardiovascular risk who had pioglitazone or placebo
      added to existing treatment. The present post hoc study analyzed lipid results
      from patients who received different baseline antihyperglycemia regimens and the
      presence or absence of baseline statin use. Independent of antihyperglycemia
      medication and statin use, triglyceride levels decreased in all subgroups treated
      with pioglitazone (-9.9% to -12.3%), whereas little change was observed in
      placebo groups. High-density lipoprotein cholesterol increased nearly twice as
      much with pioglitazone (18.1% to 20.3%) as with placebo (8.1% to 11.8%) across
      all subgroups. Low-density lipoprotein cholesterol increased moderately with
      pioglitazone (5.2% to 9.6%) compared with placebo (3.3% to 7.6%) (placebo
      adjusted range 1.11% to 4.37%). In conclusion, long-term pioglitazone therapy led
      to durable improvements in triglyceride and high-density lipoprotein cholesterol
      levels, irrespective of baseline antihyperglycemia therapy or statin use.

PMID- 19576354
TI  - Body composition, cardiorespiratory fitness, and low-grade inflammation in middle
      aged men and women.
AB  - The objective of the present study was to determine the respective contributions
      of visceral adipose tissue (AT) accumulation and cardiorespiratory fitness to
      variation of inflammatory markers in men and women. Circulating levels of C
      reactive protein, tumor necrosis factor-alpha, interleukin-6, and adiponectin
      were obtained with visceral AT (computed tomography) and fitness (physical
      working capacity test) levels in a sample of healthy men (n = 120) and women (n =
      152) covering a wide range of adiposity. An inflammation score was developed
      based on gender-specific percentile values of each inflammatory marker (0 or 1),
      which yielded a score ranging from 0 (low) to 4 (high). Visceral AT was
      positively associated with C-reactive protein and interleukin-6 levels (r > or
      =0.35, p <0.0001), but negatively associated with adiponectin (r = -0.29, p < or
      =0.0003) after adjustment for fitness. After adjusting for visceral AT, fitness
      was not associated with variation in inflammatory markers in women and only with
      adiponectin in men (r = -0.20, p = 0.03). In participants with low visceral AT
      (<130 cm(2) for men and <100 cm(2) for women), prevalences of participants with
      an increased inflammation score were 23.9% and 28.0%, respectively, for
      participants with high and low fitness, whereas in subjects with increased
      visceral AT, prevalences of a high inflammation score were 60.0% and 61.7%,
      respectively, for participants with high and low fitness. In conclusion, these
      results suggest that the previously reported association between poor fitness and
      low-grade inflammation may be largely attributable to increased visceral AT
      accumulation and its associated state of insulin resistance, conditions
      frequently observed in subjects with poor cardiorespiratory fitness.

PMID- 19576356
TI  - Feasibility and safety of same-day home discharge after radiofrequency catheter
      ablation.
AB  - Interventional cardiology in a day-case setting might reduce logistic constraints
      on hospital resources. However, in contrast with coronary angioplasty, few data
      support the feasibility and safety of radiofrequency catheter ablation (RCA). The
      aim of this prospective, multicenter cohort study was to evaluate the feasibility
      and safety of RCA in 1,342 patients (814 men; mean age 57 +/- 17 years)
      considered eligible for ambulatory RCA, according to specific set of criteria,
      for common atrial flutter (n = 632), atrioventricular nodal reentrant tachycardia
      (n = 436), accessory pathways (n = 202), and atrial tachycardia (n = 72).
      Patients suitable for early discharge (4 to 6 hours after uncomplicated RCA) were
      scheduled for 1-month follow-up. Predictive factors for delayed complications
      were studied by multivariate analysis. Of the 1,342 enrolled patients, 1,270
      (94.6%) were discharged the same day and followed for 1 month; no deaths
      occurred, and the readmission rate was 0.79% (95% confidence interval 0.30% to
      1.27%). Six patients had significant puncture complications, 2 presented with
      symptomatic delayed pulmonary embolism, and 2 had new onset of poorly tolerated
      atrial flutter. None of these complications was life threatening. Multivariate
      analysis did not identify any significant independent predictors for delayed
      complications. In conclusion, these data suggest that same-day discharge after
      uncomplicated RCA for routine supraventricular arrhythmias is safe and may be
      applicable in clinical practice. This approach is known to be associated with
      significant patient satisfaction and cost savings and can be considered a first
      line option in most patients who undergo routine ablation procedures.

PMID- 19576355
TI  - Prognostic value of multiple biomarkers in American Indians free of clinically
      overt cardiovascular disease (from the Strong Heart Study).
AB  - Several biomarkers have been documented, singly or jointly, to improve risk
      prediction, but the extent to which they improve prediction-model performance in
      populations with high prevalences of obesity and diabetes has not been
      specifically examined. The aim of this study was to evaluate the ability of
      various biomarkers to improve prediction-model performance for death and major
      cardiovascular disease (CVD) events in a high-risk population. The relations of 6
      biomarkers with outcomes were examined in 823 American Indians free of prevalent
      CVD or renal insufficiency, as were their contributions to risk prediction. In
      single-marker models adjusting for standard clinical and laboratory risk factors,
      4 of 6 biomarkers significantly predicted mortality and major CVD events. In
      multimarker models, these 4 biomarkers-urinary albumin/creatinine ratio (UACR),
      glycosylated hemoglobin, B-type natriuretic peptide, and fibrinogen-significantly
      predicted mortality, while 2-UACR and fibrinogen-significantly predicted CVD. On
      the basis of its robust association in participants with diabetes, UACR was the
      strongest predictor of mortality and CVD, individually improving model
      discrimination or classification in the entire cohort. Singly, all remaining
      biomarkers also improved risk classification for mortality and enhanced average
      sensitivity for mortality and CVD. The addition of > or =1 biomarker to the
      single marker UACR further improved discrimination or average sensitivity for
      these outcomes. In conclusion, biomarkers derived from diabetic cohorts, and
      novel biomarkers evaluated primarily in lower risk populations, improve risk
      prediction in cohorts with prevalent obesity and diabetes. Risk stratification of
      these populations with multimarker models could enhance selection for aggressive
      medical or surgical approaches to prevention.

PMID- 19576357
TI  - Value of orthopnea, paroxysmal nocturnal dyspnea, and medications in prospective
      population studies of incident heart failure.
AB  - Prospective population studies of incident heart failure (HF) are often limited
      by difficulties in assembling HF-free cohorts. In this study, public-use copies
      of the Cardiovascular Health Study (CHS) data sets were used to determine the
      sensitivity, specificity, and positive and negative predictive values of
      orthopnea and paroxysmal nocturnal dyspnea (PND), with and without the use of
      medications used in CHS HF criteria (diuretics plus digoxin or vasodilators), in
      the diagnosis of prevalent HF and in the assembly of a relatively HF-free
      population. Of the 5,771 community-dwelling older adults aged > or =65 years, 803
      had orthopnea, 660 had PND, 1,075 had either symptom, 388 had both symptoms, 547
      were using HF medications, and 4,315 had neither symptom and were not using HF
      medications. Definite HF was centrally adjudicated in 272 participants. The
      sensitivity, specificity, and positive and negative predictive values for either
      orthopnea or PND were 52% (95% confidence interval [CI] 46% to 58%), 83% (95% CI
      82% to 84%), 13% (95% CI 11% to 15%), and 97% (95% CI 97% to 98%), respectively,
      and those for either orthopnea or PND or the use of HF medications were 77% (95%
      CI 72% to 82%), 77% (95% CI 76% to 79%), 14% (95% CI 13% to 16%), and 99% (95% CI
      98% to 99%), respectively. In conclusion, only <20% of those with either
      orthopnea or PND had definite HF, which limits their usefulness in the diagnosis
      of prevalent HF in the community. However, nearly 99% (negative predictive value)
      of those with neither symptom nor using HF medications also did not have HF,
      which may be useful as a simple and inexpensive tool in assembling relatively HF
      free cohorts for prospective population studies of incident HF.

PMID- 19576358
TI  - Relation of dyspnea in patients unable to perform exercise stress testing to
      outcome and myocardial ischemia.
AB  - Limited information exists regarding the significance of dyspnea in patients who
      are unable to exercise and the contribution of myocardial ischemia to this
      symptom. To assess this, we evaluated results of dobutamine stress
      echocardiography (DSE) and long-term outcome of patients with dyspnea referred
      for DSE. We studied 6,376 consecutive patients who were unable to perform an
      exercise test and were referred for DSE. Patients were classified according to
      presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac
      ischemic events (myocardial infarction or revascularization), hospitalization for
      heart failure (HF), and death. Dobutamine stress echocardiogram was positive for
      ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with
      typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate
      analysis, risk of death was increased in dyspneic patients versus asymptomatic
      patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR
      1.20, p <0.001). Hospitalization for HF occurred more often in patients with
      dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain),
      especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain).
      Risk of cardiac ischemic events in patients with dyspnea was similar versus
      asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with
      chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE,
      dyspnea was associated with a poor outcome. This increased hazard seems not to be
      linked to myocardial ischemia, but instead to HF and death.

PMID- 19576359
TI  - Impact of alpha 1-adrenergic antagonist use for benign prostatic hypertrophy on
      outcomes in patients with heart failure.
AB  - Previous clinical trials have shown that alpha(1)-adrenergic antagonists are not
      effective in subjects with heart failure (HF) and might increase HF rates when
      used for hypertension. However, alpha(1)-adrenergic antagonists may be prescribed
      to subjects with HF who have symptomatic benign prostatic hyperplasia. We sought
      to determine any association between alpha(1)-adrenergic antagonist use, commonly
      prescribed for benign prostatic hyperplasia, and the clinical outcomes of
      subjects with HF receiving contemporary therapy. An existing database of 388
      subjects with decompensated HF admissions from 2002 to 2004 at the Veterans
      Affairs Hospital was analyzed according to the use of alpha(1)-adrenergic
      antagonists at discharge. Covariate-adjusted Cox proportional hazard models were
      used to examine any association with future admissions for decompensated HF and
      total mortality. Alpha-1-adrenergic antagonist therapy was prescribed in 25% of
      our HF population, predominantly for benign prostatic hyperplasia, and was not
      associated with significant increases in the combined risk of all-cause mortality
      and rehospitalization for HF (hazard ratio 1.24, 95% confidence interval 0.93 to
      1.65, p = 0.14), HF hospitalization (hazard ratio 1.20, 95% confidence interval
      0.85 to 1.70, p = 0.31), or all-cause mortality (hazard ratio 1.10, 95%
      confidence interval 0.78 to 1.56, p = 0.57). In patients not receiving beta
      blocker therapy, alpha(1)-adrenergic antagonist therapy was significantly
      associated with increased HF hospitalizations (hazard ratio 1.94, 95% confidence
      interval 1.14 to 3.32, p = 0.015). In conclusion, in patients with chronic HF,
      the use of alpha(1)-adrenergic antagonists was significantly associated with more
      HF hospitalizations when prescribed without concomitant beta blockade. Thus,
      background beta-blocker therapy appears to be protective against the potential
      harmful effects of alpha(1)-adrenergic antagonist therapy in patients with HF.

PMID- 19576360
TI  - Comparison of U.S. and Italian experiences with sudden cardiac deaths in young
      competitive athletes and implications for preparticipation screening strategies.
AB  - Controversy has evolved over the most practical and effective strategy for
      preparticipation cardiovascular screening of competitive athletes to detect
      unsuspected cardiovascular disease and prevent sudden death on the athletic
      field. Athlete screening in the Veneto region of Italy is part of a national
      program (with 12-lead electrocardiography) that has reported the detection of
      previously undiagnosed hypertrophic cardiomyopathy and a decrease in the
      cardiovascular death rate in young athletes. In this study, over time periods of
      similar length, cardiovascular-related mortality rates in Veneto athletes were
      compared with those of a demographically similar region of the United States
      (Minnesota) in which screening is limited to history and physical examination.
      There were 55 sudden cardiovascular deaths reported in Veneto over 26 years
      (2.1/year), compared with 22 deaths in 23 years (0.96/year) in Minnesota. Over
      the recent and comparable 11-year period, 1993 to 2004, 12 deaths were reported
      in Veneto and 11 in Minnesota. When analyzed as deaths per 100,000 person-years,
      Veneto exceeded Minnesota for all years combined (1.87 for 1979 to 2004 vs 1.06
      for 1985 to 2007, respectively, p = 0.006), although the 2 regions did not differ
      significantly for 1993 to 2004 (0.87 vs 0.93, respectively, p = 0.88) or most
      recently for 2001 to 2004 (0.43 vs 0.90, respectively, p = 0.38). In conclusion,
      sudden cardiovascular deaths in young competitive athletes occurred at a low rate
      in both Veneto and Minnesota. Despite different preparticipation screening
      strategies, athlete sudden death rates in these demographically similar regions
      of the United States and Italy have not differed significantly in recent years.
      These data do not support a lower mortality rate associated with preparticipation
      screening programs involving routine electrocardiography and examinations by
      specially trained personnel.

PMID- 19576361
TI  - Treating children with idiopathic dilated cardiomyopathy (from the Pediatric
      Cardiomyopathy Registry).
AB  - In 40% of children with symptomatic idiopathic dilated cardiomyopathy (IDC),
      medical therapy fails within 2 years of diagnosis. Strong evidence-based
      therapies are not available for these children, and how evidence-based therapies
      for adults with IDC should be applied to children is unclear. Using data from the
      National Heart, Lung, and Blood Institute's Pediatric Cardiomyopathy Registry, we
      compared practice patterns of initial therapies for children with IDC diagnosed
      from 1990 to 1995 (n = 350) and from 2000 to 2006 (n = 219). At diagnosis, 73%
      had symptomatic heart failure (HF), and 7% had > or =1 family member with IDC.
      Anti-HF medications were most commonly prescribed initially. Anti-HF medication
      use was similar across the 2 periods (84% and 87%, respectively), as was
      angiotensin-converting enzyme inhibitor use (66% and 70%, respectively). These
      medications were used more commonly in children with greater left ventricular
      dilation and poorer left ventricular fractional shortening and functional class
      (p <0.001). Beta-blocker use was 4% to 18% over the 2 periods. Treatments for
      pediatric IDC have changed little over the previous 25 years. Anti-HF medications
      remain the most common treatment, and they are often given to children with
      asymptomatic left ventricular dysfunction. Children with asymptomatic left
      ventricular dysfunction are often not offered angiotensin-converting enzyme
      inhibitors without echocardiographic evidence of advanced disease. In conclusion,
      therapeutic clinical trials are strongly indicated because practice variation is
      substantial and medical outcomes in these children have not improved in the
      previous several decades.

PMID- 19576362
TI  - Usefulness of natriuretic peptide testing for long-term risk assessment following
      acute ischemic stroke.
AB  - Acute-phase levels of B-type natriuretic peptide (BNP) and the N-terminal
      fragment of the BNP prohormone (NT-pro-BNP) have been associated with mortality
      when measured in patients with an acute ischemic stroke; however, data regarding
      the longer-term value of NT-pro-BNP for long-term prognostication after ischemic
      stroke are limited. Two hundred sixteen patients (mean age 67 +/- 13 years) with
      acute ischemic stroke were seen 6 months after index admission at which time a
      structured evaluation including measurement of plasma NT-pro-BNP was performed.
      Patients were followed for 45 months, with all-cause mortality as the clinical
      end point. Median NT-pro-BNP concentration for the entire group was 147 pg/ml
      (10th to 90th percentiles 37 to 869). At follow-up 45 patients (21%) had died. NT
      pro-BNP concentrations were significantly higher in decedents (308 pg/ml, 10th to
      90th percentiles 74 to 2,279) than in the 171 survivors (132 pg/ml, 10th to 90th
      percentiles 35 to 570, p <0.001). Patients with NT-pro-BNP < or =147 pg/ml had a
      significantly improved survival rate on univariate analysis (p <0.001). In
      multivariate analysis after adjustment for age, stroke severity, heart and renal
      failures, levels of NT-pro-BNP were an independent predictor of mortality >6
      months after stroke (adjusted hazard ratio 1.5, 95% confidence interval 1.1 to
      1.9, p = 0.005). In conclusion, NT-pro-BNP concentrations measured during the
      stable phase after acute ischemic stroke are strongly predictive of long-term
      mortality.

PMID- 19576363
TI  - Contribution of bleeding and thromboembolic events to in-hospital mortality among
      patients with thrombocytopenia treated with heparin.
AB  - In a population of patients experiencing thrombocytopenia while treated with
      heparin, bleeding and thromboses are well-appreciated complications, but their
      relative contributions to mortality have been less well described. In this
      population, the aims of this study were (1) to identify the independent
      predictors of bleeding and (2) to compare the incidence and the strength of
      association of bleeding and of new thromboses to in-hospital mortality. The
      independent predictors of bleeding and in-hospital mortality were identified
      using multivariate logistic regression models on the 1,478 patients who developed
      thrombocytopenia after their enrollment in the Complications After
      Thrombocytopenia Caused by Heparin (CATCH) study. The independent predictors of
      bleeding were chronic hematologic disorders, intra-aortic balloon pump,
      congestive heart failure, and platelet count nadir <120 x 10(9)/L. Although
      bleeding (n = 141 [10%]) and thromboembolic complications (n = 135 [9%]) were
      equally prevalent, the former was less strongly associated than the latter with
      in-hospital mortality (odds ratio 1.75, 95% confidence interval 1.01 to 3.03, and
      odds ratio 2.77, 95% confidence interval 1.67 to 4.61, respectively). In
      conclusion, medical management should be directed mainly at the prevention of
      thromboembolic complications, while additionally considering the risk for
      bleeding.

PMID- 19576364
TI  - Ectopic pregnancy in a uterine perforation site.
AB  - Uterine perforation can occur following first-trimester abortion or more commonly
      postpartum after evacuation of retained placental tissues. We report a case of a
      pregnancy at the site of a recent uterine perforation. Possible mechanisms of
      this rare condition and different therapeutic options are mentioned.

PMID- 19576365
TI  - Discussion: 'Microcephaly associated with congenital heart defect' by Barbu et
      al.
AB  - In the roundtable that follows, clinicians discuss a study published in this
      issue of the Journal in light of its methodology, relevance to practice, and
      implications for future research. Article discussed: Barbu D, Mert I, Kruger M,
      Bahado-Singh RO. Evidence of fetal central nervous system injury in isolated
      congenital heart defect: microcephaly at birth. Am J Obstet Gynecol
      2009;201:43.e1-7.

PMID- 19576366
TI  - The state of the American Journal of Obstetrics & Gynecology: 2009.

PMID- 19576367
TI  - The "Vitamin D Council" advertisement.

PMID- 19576368
TI  - Professional integrity, respect for autonomy, and the self-regulation of
      reproductive endocrinology.

PMID- 19576369
TI  - The role of transvaginal ultrasound or endometrial biopsy in the evaluation of
      the menopausal endometrium.
AB  - All postmenopausal women with vaginal bleeding need endometrial assessment.
      Disposable suction piston biopsy devices have virtually replaced dilatation and
      curettage despite little scientific validation. In patients with known carcinoma,
      false-negative rates with such devices range from 2.5-32.4%. Large prospective
      studies have shown that an endometrial thickness <or= 4 mm on transvaginal
      ultrasound in postmenopausal women with bleeding has a risk of malignancy of 1 in
      917. Thus, in postmenopausal patients with bleeding, biopsy is not indicted when
      endometrial thickness is <or= 4 mm. The significance of a thick endometrial echo
      in nonbleeding postmenopausal women has not been validated and need not require
      automatic tissue sampling.

PMID- 19576370
TI  - The California octuplets and the duties of reproductive endocrinologists.
AB  - The recent birth of octuplets unleashed a firestorm of publicity, casting a harsh
      light on the mother and her presumed inadequacies as a parent. It also raised
      questions about the role of reproductive endocrinologists. Herein we consider 3
      aspects of this question: should reproductive endocrinologists consider the
      economic interests of society, should they consider parenting abilities, and
      should the number of embryos transferred be limited? We conclude that the ethical
      obligation of reproductive endocrinologists does not extend to protection of
      society's economic interests; that reproductive endocrinologists, although poorly
      trained and situated to gauge an individual's ability to parent, can in extreme
      circumstances refuse to provide assisted reproductive technology; and that a firm
      limit on the number of transferred embryos is ethically and medically
      appropriate.

PMID- 19576371
TI  - A customized standard to assess fetal growth in a US population.
AB  - OBJECTIVE: The objective of the study was to assess the factors that affect fetal
      growth and birthweight, and to derive coefficients for a customized growth chart
      applicable in an American population. STUDY DESIGN: This was a prospective cohort
      study of 35,235 pregnancies. Coefficients for physiological and pathological
      variables were derived by backward multiple regression. RESULTS: The expected
      birthweight at 40.0 weeks for a standard-size primiparous mother of European
      origin in an uncomplicated pregnancy was 3453.4 g, very similar to the
      standardized birthweight observed in other populations. Physiological
      coefficients were derived for maternal height, weight, parity, ethnic origin, and
      sex of the baby. Smoking, history of preterm delivery, and hypertensive diseases
      in the current pregnancy all had negative effects on birthweight, whereas babies
      of diabetic mothers weighed more. Low as well as high body mass index was
      associated with birthweight deficit at term. CONCLUSION: Coefficients that allow
      determination of the customized growth potential, individually adjusted and
      excluding known pathological factors, have been derived. Babies of obese mothers
      have an increased risk of not reaching their fetal growth potential.

PMID- 19576372
TI  - Adverse pregnancy outcome and association with small for gestational age
      birthweight by customized and population-based percentiles.
AB  - OBJECTIVE: The objective of the study was to investigate the association between
      pregnancy complications and small for gestational age (SGA) birthweight,
      comparing SGA based on the customized growth potential with SGA based on the
      birthweight standard of the same population. STUDY DESIGN: This was a
      retrospective analysis of a database from a US multicenter study. Pregnancy
      complications included threatened preterm labor, antepartum hemorrhage, pregnancy
      induced hypertension, preeclampsia, stillbirth, and early neonatal death.
      RESULTS: Compared with SGA by the birthweight standard, SGA by customized growth
      potential showed higher risk for each of the 6 adverse indicators. A third of the
      SGA group was small by customized centiles but not by population-based centiles,
      yet was strongly associated with each of the pregnancy complications studied.
      This subgroup of unrecognized SGA babies included 26% preterm deliveries. In
      contrast, a subgroup that was SGA by the population standard but not by the
      customized standard (17.2%), was not associated with any of the indicators of
      adverse outcome. CONCLUSION: SGA defined by customized growth potential improves
      the differentiation between physiologically and pathologically small babies.

PMID- 19576373
TI  - High pregnancy weight gain and risk of excessive fetal growth.
AB  - OBJECTIVE: The purpose of this study was too assess whether prepregnancy body
      mass index (BMI) modifies the relationship between pregnancy weight gain and
      large for gestational age (LGA; > 90% of birthweight for gestational age) or
      macrosomia (>or= 4500 g). STUDY DESIGN: This was a population-based cohort study
      of 104,980 singleton, term births from 2000-2005. RESULTS: Prepregnancy BMI
      modified the relationship between weight gain and LGA. Lean women had higher odds
      of LGA than overweight or obese women for weight gain >or= 36 lb. For macrosomia,
      prepregnancy BMI did not modify the association. Compared with women who gained
      15-25 lb, the aOR for a gain of 26-35 lb was 1.5 (95% confidence interval [CI],
      1.2-1.9), for a gain of 36-45 lb was 2.1 (95% CI, 1.7-2.7), and for a gain of
      >or= 46 lb was 3.9 (95% CI, 3.0-5.0). CONCLUSION: Current pregnancy weight gain
      recommendations include weight gain ranges that are associated with increased
      risk of LGA and macrosomia.

PMID- 19576374
TI  - Low pregnancy weight gain and small for gestational age: a comparison of the
      association using 3 different measures of small for gestational age.
AB  - OBJECTIVE: The purpose of this study was to assess associations between pregnancy
      weight gain (PWG) and small for gestational age (SGA) defined by birthweight <
      10th percentile and 2 more restrictive definitions and to assess the proportion
      of SGA attributed to low PWG. STUDY DESIGN: This was a retrospective cohort study
      of 104,980 singleton, term births from the 2000-2005 Pregnancy Risk Assessment
      Monitoring System (PRAMS). RESULTS: Compared with women who gained 15-25 lbs
      during pregnancy, women who gained 1-14 lbs had 1.5 greater odds (95% confidence
      interval, 1.2-1.8) of SGA for the most restrictive definition and 1.2 greater
      odds (95% confidence interval, 1.1-1.4) for the least restrictive definition,
      after adjustments for confounders. Depending upon the definition used, PWG below
      current Institute of Medicine recommendations contributed to 10-15% of SGA,
      representing 0.8-1.2% of all singleton term infants. CONCLUSION: Associations
      between low PWG and SGA varied little by definition of SGA and contributed to
      only a small proportion of term SGA infants.

PMID- 19576375
TI  - Adhesion development and morbidity after repeat cesarean delivery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the development and
      implications of intraabdominal adhesions after repeat cesarean section delivery
      (CS). STUDY DESIGN: We reviewed the charts of 1283 women who underwent repeat CS
      and 203 other women who underwent primary CS. Primary outcome measures were
      incidence and extent of adhesions, incision-to-delivery interval, and operating
      time. RESULTS: No adhesions were found in primary CS. Compared with those women
      with a second CS (24.4%), significantly more women had adhesions after 3 CSs
      (42.8%; 95% confidence interval [CI], 0.84-0.99). Compared with a first CS (7.7
      +/- 0.3 minutes), the delivery time was significantly longer at subsequent CSs
      (second CS, 9.4 +/- 0.1 minutes; 95% CI, 1-2; third CS, 10.6 +/- 0.3 minutes; 95%
      CI, 2-4; >or= 4 CSs, 10.4 +/- 0.1 minutes; 95% CI, 1-2). However, complication
      rates in those women with >or= 2 CSs were comparable with primary CS. CONCLUSION:
      Increased adhesion development and a longer time to delivery were found with each
      subsequent CS.

PMID- 19576376
TI  - Abdominal cerclage for the treatment of recurrent cervical insufficiency:
      laparoscopy or laparotomy?
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of traditional
      abdominal cerclage (AC) with laparoscopic cerclage (LC). STUDY DESIGN: Eligible
      women had at least 1 second trimester pregnancy loss due to cervical
      insufficiency, and had undergone at least 1 failed transvaginal cerclage. A
      prospective cohort of patients undergoing LC was compared with a historical
      control group of patients who had AC. A successful primary outcome was defined as
      delivery of a viable infant with neonatal survival. RESULTS: We were able to
      evaluate 19 pregnancies following unique abdominal cerclage placement, 12
      laparoscopic and 7 at the time of laparotomy. Nine of 12 (75%) undergoing LC and
      5 of 7 (71%) pregnancies undergoing AC successfully delivered a viable infant (P
      = .63). LC during pregnancy was successful in 4 of 5 (80%) cases as compared to 3
      of 5 (60%) cases with AC during pregnancy (P = 1.0). CONCLUSION: Operative
      laparoscopy is a safe and effective alternative to laparotomy for the placement
      of abdominal cerclage.

PMID- 19576377
TI  - Prediction of risk for cesarean delivery in term nulliparas: a comparison of
      neural network and multiple logistic regression models.
AB  - OBJECTIVE: We sought to develop a neural network (NN) to predict the risk for
      cesarean delivery (CD) in term nulliparas. STUDY DESIGN: Using software
      (BrainMaker for Windows, Version 3.0; California Scientific Software, Nevada
      City, CA), we trained an NN with 225 patients obtained by chart review and
      included for nulliparity, singleton vertex > 36 weeks' gestation, and reassuring
      fetal heart rate on admission. Training inputs included several maternal and
      fetal clinical variables. Two logistic regression (LR) models using 225 and 600
      patients (LR225 and LR600, respectively) were developed. The NN and LR models
      were tested for prediction of CD in a set of 100 patients not used for
      development. RESULTS: The NN, LR225, and LR600 correctly predicted 53%, 26%, and
      32% of the patients with CD and 88%, 95%, and 95% of the patients with vaginal
      delivery, respectively. CONCLUSION: Compared with LRs, the NN was slightly better
      in predicting CD and was similar for predicting vaginal delivery in nulliparas
      with term singletons.

PMID- 19576378
TI  - Evaluation of the porcine model to teach various ancillary procedures to
      gynecologic oncology fellows.
AB  - OBJECTIVE: The purpose of this study was to subjectively evaluate the adequacy of
      the porcine model for training gynecologic oncology fellows. STUDY DESIGN:
      Following a defined surgical curriculum, fellow-attending pairs operated on
      female hogs. A predetermined dataset was collected for each procedure. RESULTS:
      Twenty pigs were operated on. The porcine model was determined to be a good model
      for laparoscopic lymphadenectomy (11), ureteroneocystostomy (7), repair of
      vascular injury (11), bowel anastamoses (21), distal pancreatectomy (5),
      nephrectomy (6), partial hepatectomy (5), diaphram stripping (5), and
      diaphragmatic resection (4). Two attendings and 1 fellow judged the porcine model
      to be fair (remaining 11 good) for ileocolonic urinary diversion, mainly due to
      significant differences in anatomy. Liver mobilization (5) and splenectomy (11)
      were determined to be fair or poor models by all participants due to the limited
      attachments in the pig. CONCLUSION: The porcine model is adequate for teaching
      some ancillary gynecologic oncology surgical procedures and is inadequate for
      others.

PMID- 19576380
TI  - Determination of HIV drugs in biological matrices: a review.
AB  - The present paper reviews the recent advances on the determination of
      antiretroviral drugs against the human immunodeficiency virus (HIV). Methods have
      been reviewed with special emphasis on the principal analytical strategies for
      dealing with clinical samples as well as the determination of the newest drugs.
      The most critical steps of the analytical procedures including the sample
      treatment, separation and validation have been discussed. Finally, a brief
      description of representative applications is given.

PMID- 19576381
TI  - Review: bioanalytical applications of biomolecule-functionalized nanometer-sized
      doped silica particles.
AB  - Recent research has looked to develop innovative and powerful novel
      biofunctionalized nanometer-sized silica particles, controlling and tailoring
      their properties in a very predictable manner to meet the needs of specific
      applications. The silica shells of these particles facilitate a wide variety of
      surface reactions and allow conjugation with biomolecules like proteins and DNA.
      There exist a multitude of possible applications of fabricated nanoparticles in
      biotechnology and medicine. In particular, they have proved to be highly useful
      for biosensing, assay labelling, bioimaging, and in research on a variety of
      molecular tags in cellular and molecular biology. Techniques commonly rely on the
      use of silica-coated semiconductor quantum dots, organic dyes, magnetic
      particles, and Raman active particles. Inorganic-biological hybrid particles
      combine the properties of both materials, i.e., the spectroscopic characteristics
      of the entrapped nanocrystal, and the biomolecular function of the conjugated
      entity. Rather than being exhaustive, this review focuses on selected examples to
      illustrate novel concepts and promising applications. Approaches described
      include the encoding of silica nanoparticles with different groups, and
      conjugation with various biological entities. Further, promising applications in
      bioanalysis are considered and discussed.

PMID- 19576382
TI  - Tutorial: the modelling of chemical processes.
AB  - The modelling of chemical processes entails the computation of the concentration
      profiles of all reaction species as a function of the reaction time. The basis
      for the calculations is the system of differential equations (ODE's) that is
      defined by the reaction mechanism. Most textbooks on chemical kinetics
      concentrate on those few reaction mechanisms that lead to ODE's with explicit
      solutions. In this tutorial, we demonstrate that numerical integration is a
      viable alternative, that it can be applied to any mechanism, and that it is easy
      to do so. Matlab example programs illustrate the concepts and they allow the
      reader to explore the effects of changing conditions such as initial
      concentrations or rate constants etc. Example reaction mechanisms include a zero
      th order enzymatic reaction and reactions at non-constant temperature and pH.

PMID- 19576383
TI  - Fermentation condition outweighed truffle species in affecting volatile organic
      compounds analyzed by chromatographic fingerprint system.
AB  - The influences of fermentation conditions and truffle species (i.e., Tuber
      melanosporum, Tuber sinense, Tuber indicum, and Tuber aestivum) on the volatile
      organic compounds (VOCs) originated from truffle fermentation mycelia were
      studied by using chromatographic fingerprint system for the first time. Gas
      chromatography combined with statistical methods including similarity analysis
      and hierarchical cluster analysis was applied to develop chromatographic
      fingerprint system for truffle VOCs evaluation. Fermentation conditions affected
      the VOCs from truffle fermentation mycelia much more significantly than truffle
      species. This indicated that it is possible to adjust the aroma of truffle
      fermentation mycelia similar with the natural fruiting-body through the control
      of fermentation process.

PMID- 19576384
TI  - Two-dimensional wavelet analysis based classification of gas chromatogram
      differential mobility spectrometry signals.
AB  - This study introduces two-dimensional (2-D) wavelet analysis to the
      classification of gas chromatogram differential mobility spectrometry (GC/DMS)
      data which are composed of retention time, compensation voltage, and
      corresponding intensities. One reported method to process such large data sets is
      to convert 2-D signals to 1-D signals by summing intensities either across
      retention time or compensation voltage, but it can lose important signal
      information in one data dimension. A 2-D wavelet analysis approach keeps the 2-D
      structure of original signals, while significantly reducing data size. We applied
      this feature extraction method to 2-D GC/DMS signals measured from control and
      disordered fruit and then employed two typical classification algorithms to
      testify the effects of the resultant features on chemical pattern recognition.
      Yielding a 93.3% accuracy of separating data from control and disordered fruit
      samples, 2-D wavelet analysis not only proves its feasibility to extract feature
      from original 2-D signals but also shows its superiority over the conventional
      feature extraction methods including converting 2-D to 1-D and selecting
      distinguishable pixels from training set. Furthermore, this process does not
      require coupling with specific pattern recognition methods, which may help ensure
      wide applications of this method to 2-D spectrometry data.

PMID- 19576385
TI  - Analysis of the factors that significantly influence the stability of
      fluoroquinolone-metal complexes.
AB  - The aim of the present study was to evaluate factors contributing to the
      differences between the overall stability constants (logbeta(pqr)) of the
      fluoroquinolone-metal ion complexes. The experiments were performed using
      potentiometric titration method in wide pH range. The overall stability constants
      (logbeta(pqr)) were determined using the Hyperquad program. Complexation
      equilibria of eight different fluoroquinolones with six divalent and trivalent
      metal ions were investigated in this study. The authors employed a multifactorial
      ANOVA analysis, fixed effect model to describe the influence of particular
      variables affecting the stability of the analyzed complex species. Four different
      variables were set at different levels labeled. The ligand number (LF) was the
      first factor. LF determined the number of fluorochinolone molecules in the
      complex structure, and could take the values 1, 2 or 3. The second factor (Me)
      was connected with the type of the metal ion bonded in the complex. Since six
      different metal cations were studied, the Me factor was described with six
      levels. The number of hydrogen or hydroxide groups substituted into the complex
      molecule was the third variable (HR) with many levels labeled: q, a, s, d, f and
      g. The last factor FQ described the type of the fluorochinolone used for complex
      formations. All variables analyzed here were statistically significant (p value
      lower than 0.01), which indicates that all of them strongly affect the
      logbeta(pqr) value. Binary interactions (LF-Me, LF-FQ, Me-HR and Me-FQ) between
      variables were also stated, which suggests that the effects of these variables
      were higher than we could calculate based on the effect of each variable alone.
      The ANOVA analysis has shown that the following factors Me, LF and HR were the
      most important for the stability of the fluoroquinolone-metal ion complexes. It
      was also found that according to the FQ factor (type of ligand molecule) all
      analyzed fluoroquinolones formed stable complexes with metals. It was proved that
      the application of ANOVA for the entire complexation profile of analyzed
      fluoroquinolones with polyvalent metal ions was a valid technique for detecting
      the statistically significant differences in the complexation profiles. Such
      information may be very useful for better understanding and interpretation of
      differences in bioavailability of fluoroquinolones and their interactions with
      antacids and other multimineral drugs.

PMID- 19576386
TI  - Fabrication of a new electrochemiluminescent sensor for fentanyl citrate based on
      glassy carbon microspheres and ionic liquid composite paste electrode.
AB  - Due to the high performance of glassy carbon in the aspects of mechanical
      strength, electrical conductivity and high corrosion resistance, etc., glassy
      carbon has been widely used in the electrochemistry. A new form of glassy carbon,
      glassy carbon microsphere, was utilized to couple with ionic liquid in preparing
      a new electrochemiluminescent platform for Ru(bpy)3Cl2. Room temperature ionic
      liquid has been proposed to be very interesting and efficient pasting binder to
      replace the non conductive organic binders for the fabrication of composite paste
      electrode. Attributed to the special characteristics of glassy carbon
      microspheres and room temperature ionic liquid [N-octylpyridium tetrafluoroborate
      (OPFP)], this new electrochemiluminescent sensor exhibited excellent
      electrochemiluminescent performance in Ru(bpy)(3)(2+) solution. We first found
      that fentanyl citrate could increase the ECL of Ru(bpy)(3)(2+), hence an ECL
      approach was developed for the determination of fentanyl citrate based on this
      glassy carbon microspheres based electrochemiluminescent platform with high
      sensitivity. Under the optimized conditions, the enhanced electrochemiluminescent
      intensity versus fentanyl citrate concentration was linear in the range of 1.0 x
      10(-8) to 1.0 x 10(-4) mol L(-1) with a detection limit of 8.5 x 10(-9) mol L(
      1), and the relative standard deviation for 1.0 x 10(-6) mol L(-1) fentanyl
      citrate was 1.90% (n = 10). This protocol has extended the application scopes of
      glassy carbon material and promoted the application of glassy carbon microspheres
      in electroanalysis.

PMID- 19576387
TI  - Comparative studies of neodymium (III)-selective PVC membrane sensors.
AB  - Sensors based on two neutral ionophores, N,N'-bis((1H-pyrrol-2
      yl)methylene)cyclohexane-1,2-diamine (L1) and 3,3'-(cyclohexane-1,2-diylbis(azan
      1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(5-hydroxymethyl)pyridine-2-ol) (L2)
      are described for quantification of neodymium (III). Effect of various
      plasticizers; 2-nitrophenyloctylether (o-NPOE), dibutyl butylphosphonate (DBBP),
      tri-n-butyl phosphates (TBP), dioctylpthalate (DOP) and chloronapthalen (CN) and
      anion excluder, sodiumtetraphenylborate (NaTPB) has been studied. The membrane
      composition of PVC:o-NPOE:ionophore (L1):NaTPB (w/w; mg) of 150:300:5:5 exhibited
      best performance. The sensor with ionophore (L1) exhibits significantly enhanced
      selectivity towards neodymium (III) in the concentration range 5.0 x 10(-7) to
      1.0 x 10(-2) M with a detection limit of 1.0 x 10(-7) M and a Nernstian
      compliance (19.8 +/- 0.3 mV decade(-1) of activity) within pH range 4.0-8.0. The
      response time of sensor was found as 10s. The influence of the membrane
      composition and possible interfering ions has also been investigated on the
      response properties of the electrode. The fast and stable response, good
      reproducibility and long-term stability of the sensor are observed. The sensor
      has been found to work satisfactorily in partially non-aqueous media up to 20%
      (v/v) content of methanol, ethanol or acetonitrile and could be used for a period
      of 3 months. The selectivity coefficients determined by using fixed interference
      method (FIM) indicate high selectivity for neodymium. The proposed electrode
      shows fairly good discrimination of neodymium (III) from other cations. The
      application of prepared sensor has been demonstrated in the determination of
      neodymium (III) in spiked water samples.

PMID- 19576388
TI  - Ultrasonic nebulization extraction coupled with headspace single drop
      microextraction and gas chromatography-mass spectrometry for analysis of the
      essential oil in Cuminum cyminum L.
AB  - A novel method for analysis of essential oil in Cuminum cyminum L. using
      simultaneous ultrasonic nebulization extraction and headspace single drop
      microextraction (UNE-HS-SDME) followed by gas chromatography-mass spectrometry
      was developed. Experimental parameters, including the kind of suspended solvent,
      microdrop volume, sample amount, extraction time, enrichment time and salt
      concentration were examined and optimized. Compared with hydrodistillation (HD),
      UNE-HS-SDME provides the advantages of a small amount of sample (50 mg), time
      saving (20 min), simplicity, cheapness and low toxicity. In addition, UNE-HS-SDME
      also provided higher enrichment efficiency and sensitivity compared with stirring
      extraction (SE)-HS-SDME, ultrasonic assistant extraction (UAE) and UNE. Some
      constituents in the essential oil, were identified and the detection limits for
      beta-pinene, p-cymene and gamma-terpinene range from 6.67 pLL(-1) to 14.8 pLL(
      1). The results indicated that the UNE-HS-SDME is simple and highly efficient
      extraction and enrichment technique.

PMID- 19576389
TI  - Portable microfluidic system for determination of urinary creatinine.
AB  - A simple, low cost and portable microfluidic system based on a two-point alkaline
      picrate kinetic reaction has been developed for the determination of urinary
      creatinine. The creatinine reacts with picric acid under alkaline conditions,
      forming an orange-red colour, which is monitored on PDMS microchip using a
      portable miniature fibre optic spectrometer at 510 nm. A linear range was
      displayed from 0 to 40 mg L(-1) creatinine (r2 = 0.997) with a detection limit of
      3.3 mg L(-1) (S/N = 3). On-chip absorbance signals are reproducible, with
      relative standard deviations (RSDs) of 7.1%, when evaluated with 20 mg L(-1)
      creatinine (n = 10). The standard curves in which the intra-run CVs (4.7-6.8%)
      and inter-run CVs (7.9%) obtained were performed on three different days and
      exhibited good reproducibility. The method was highly correlated with the
      conventional spectrophotometric method when real urine samples were evaluated (r2
      = 0.948; n = 15).

PMID- 19576390
TI  - Dual optoelectronic visual detection and quantification of spectroscopically
      silent heavy metal toxins: a multi-measurand sensing strategy based on Rhodamine
      6G as chromo or fluoro ionophore.
AB  - A novel colorimetric chemo-sensor for the simultaneous visual detection and
      quantification of spectroscopically silent heavy metal toxins viz. cadmium, lead
      and mercury has been developed. This is based on the proposed sequential ligand
      exchange (SLE) mechanism of iodide from Pb-I(-)-Rhodamine 6G ion associate with
      citrate (without affecting ion associates of Cd and Hg) and subsequently from Cd
      I(-)-Rhodamine 6G ion associate with EDTA (without affecting Hg-I(-)-Rhodamine
      6G). Multi-measurand detection and quantification by colorimetry is possible as
      the individual toxins gives identical bathochromic shifts in aqueous solution,
      i.e. from 530 to 575 nm on formation of ternary ion associates in singular,
      binary and ternary mixtures. The visual detection provides a simple, quick and
      sensitive detection method in addition to quantification via spectrophotometry
      with Sandell sensitivities of 1.1, 15 and 2.5 microg dm(-2) for cadmium, lead and
      mercury, respectively. The developed procedure has been successfully tested for
      the analysis of environmental (cast alkali, lead acid battery and zinc
      manufacturing industry effluents) samples. Furthermore, the multi-measurand
      quantification of the above-mentioned heavy metal toxins based on fluorescence
      quenching and use of Pyronine G as chromo-ionophore instead of Rhodamine 6G is
      also described.

PMID- 19576391
TI  - Production and characterization of a broad-specificity polyclonal antibody for
      O,O-diethyl organophosphorus pesticides and a quantitative structure-activity
      relationship study of antibody recognition.
AB  - Polyclonal antibody (PAb) with broad-specificity for O,O-diethyl organophosphorus
      pesticides (OPs) against a generic hapten, 4-(diethoxyphosphorothioyloxy)benzoic
      acid, was produced. The obtained PAb showed high sensitivity to seven commonly
      used O,O-diethyl OPs in a competitive indirect enzyme-linked immunosorbent assay
      (ciELISA) using a heterologous coating antigen, 4-(3
      (diethoxyphosphorothioyloxy)phenylamino)-4-oxobutanoic acid. The 50% inhibition
      value (IC50) was 348 ng mL(-1) for parathion, 13 ng mL(-1) for coumaphos, 22 ng
      mL(-1) for quinalphos, 35 ng mL(-1) for triazophos, 751 ng mL(-1) for phorate,
      850 ng mL(-1) for dichlofenthion, and 1301 ng mL(-1) for phoxim. The limit of
      detection (LOD) met the ideal detection criteria of all the seven OP residues. A
      quantitative structure-activity relationship (QSAR) model was constructed to
      study the mechanism of antibody recognition using multiple linear regression
      analysis. The results indicated that the frontier-orbital energies (energy of the
      highest occupied molecular orbital, E(HOMO), and energy of the lowest unoccupied
      molecular orbital, E(LUMO)) and hydrophobicity (log of the octanol/water
      partition coefficient, log P) were mainly responsible for the antibody
      recognition. The linear equation was log(IC50) = -63.274E(HOMO) + 15.985E(LUMO) +
      0.556 log P-25.015, with a determination coefficient (r2) of 0.908.

PMID- 19576392
TI  - Simultaneous determination of epinephrine, uric acid and xanthine in the presence
      of ascorbic acid using an ultrathin polymer film of 5-amino-1,3,4-thiadiazole-2
      thiol modified electrode.
AB  - This paper describes the simultaneous determination of epinephrine (EP), uric
      acid (UA) and xanthine (XN) in the presence of ascorbic acid (AA) using
      electropolymerized ultrathin film of 5-amino-1,3,4-thiadiazole-2-thiol (p-ATT)
      modified glassy carbon (GC) electrode in 0.2 M phosphate buffer solution (pH 5).
      Although bare GC electrode resolves the voltammetric signals of AA and XN, it
      fails to resolve the voltammetric signals of EP and UA in a mixture. However, the
      p-ATT modified electrode not only separates the voltammetric signals of AA, EP,
      UA and XN with potential difference of 150, 120 and 400 mV between AA-EP, EP-UA
      and UA-XN, respectively but also shows higher oxidation current for these
      molecules. The p-ATT modified electrode exhibits excellent selectivity towards
      the oxidation of EP, UA and XN in the presence of 40-fold higher concentration of
      AA. Further, the p-ATT modified electrode was also used for the selective
      determination of EP in the presence of 40-fold higher concentrations of AA, UA
      and XN. Using amperometric method, we achieved the lowest detection of 40 nM EP
      and 60nM each UA and XN. The amperometric current response was increased linearly
      with increasing EP concentration in the range of 4.0 x 10(-8) to 4.0 x 10(-5) M
      and the detection limit was found to be 27 x 10(-11) M (S/N = 3). The practical
      application of the present modified electrode was demonstrated by determining the
      concentration of EP in epinephrine tartrate injection and XN in human urine
      samples.

PMID- 19576393
TI  - Combination of off-line solid-phase extraction and on-column sample stacking for
      sensitive determination of parabens and p-hydroxybenzoic acid in waters by non
      aqueous capillary electrophoresis.
AB  - For the first time, a procedure based on solid-phase extraction (SPE) for the
      simultaneous extraction of a group of parabens (methyl, ethyl, propyl, butyl and
      benzyl p-hydroxybenzoates) and p-hydroxybenzoic acid (PHBA), from environmental
      water samples has been developed. Analysis of the extracts was performed by non
      aqueous capillary electrophoresis (NACE) coupled with diode array detection
      (DAD), using large-volume sample stacking (LVSS) based on the electroosmotic flow
      pump as on-column preconcentration technique. Several water samples, such as tap,
      river, and wastewater samples, were analyzed using both SPE-NACE-DAD and SPE-LVSS
      NACE-DAD methods. It has been observed that in addition to SPE parameters such as
      sorbent material, sample pH, breakthrough volume, addition of an organic solvent
      and elution solvent, also sample characteristics, such as organic matter content,
      have influence on SPE extraction yields, especially in the case of PHBA. The
      presence of PHBA and some parabens was detected at trace levels in surface water
      samples. Concentrations up to 8.4 ng mL(-1) were found in raw wastewater, with
      the highest levels corresponding to methylparaben, propylparaben, and their main
      degradation product, PHBA.

PMID- 19576394
TI  - Microvolume turbidimetry for rapid and sensitive determination of the acid labile
      sulfide fraction in waters after headspace single-drop microextraction with in
      situ generation of volatile hydrogen sulfide.
AB  - In this work, we demonstrate the feasibility of applying headspace single-drop
      microextraction with in-drop precipitation for the quantitative determination of
      the acid labile sulfide fraction (H2S, HS-, and S2- (free sulfide), amorphous FeS
      and some metal sulfide complexes-clusters as ZnS) in aqueous samples by
      microvolume turbidimetry. The methodology lies in the in situ hydrogen sulfide
      generation and subsequent sequestration into an alkaline microdrop containing
      ZnO(2)(2-) and exposed to the headspace above the stirred aqueous sample. The ZnS
      formed in the drop was then determined by microvolume turbidimetry. The optimum
      experimental conditions of the proposed method were: 2 microL of a microdrop
      containing 750 mg L(-1) Zn(II) in 1 mol L(-1) NaOH exposed to the headspace of a
      20-mL aqueous sample stirred at 1600 rpm during 80 s after derivatization with 1
      mL of 6 mol L(-1) HCl. An enrichment factor of 1710 was achieved in only 80 s.
      The calibration graph was linear in the range of 5-100 microg L(-1) with a
      detection limit of 0.5 microg L(-1). The repeatability, expressed as relative
      standard deviation, was 5.8% (N = 9). Finally, the proposed methodology was
      successfully applied to the determination of the acid labile sulfide fraction in
      different natural water samples.

PMID- 19576395
TI  - Development of a model for the rational design of molecular imprinted polymer:
      computational approach for combined molecular dynamics/quantum mechanics
      calculations.
AB  - A new rational approach for the preparation of molecularly imprinted polymer
      (MIP) based on the combination of molecular dynamics (MD) simulations and quantum
      mechanics (QM) calculations is described in this work. Before performing
      molecular modeling, a virtual library of functional monomers was created
      containing forty frequently used monomers. The MD simulations were first
      conducted to screen the top three monomers from virtual library in each porogen
      acetonitrile, chloroform and carbon tetrachloride. QM simulations were then
      performed with an aim to select the optimum monomer and progen solvent in which
      the QM simulations were carried out; the monomers giving the highest binding
      energies were chosen as the candidate to prepare MIP in its corresponding
      solvent. The acetochlor, a widely used herbicide, was chosen as the target
      analyte. According to the theoretical calculation results, the MIP with
      acetochlor as template was prepared by emulsion polymerization method using N,N
      methylene bisacrylamide (MBAAM) as functional monomer and divinylbenzene (DVB) as
      cross-linker in chloroform. The synthesized MIP was then tested by equilibrium
      adsorption method, and the MIP demonstrated high removal efficiency to the
      acetochlor. Mulliken charge distribution and 1H NMR spectroscopy of the
      synthesized MIP provided insight on the nature of recognition during the
      imprinting process probing the governing interactions for selective binding site
      formation at a molecular level. We think the computer simulation method first
      proposed in this paper is a novel and reliable method for the design and
      synthesis of MIP.

PMID- 19576396
TI  - [Wegener granulomatosis and cocaine-induced midline destructive lesion:
      differential diagnosis].

PMID- 19576397
TI  - The anterior approach for hip reconstruction. Preface.

PMID- 19576398
TI  - The history of the anterior approach to the hip.
AB  - The anterior approach is a safe, reliable, and feasible technique for total hip
      arthroplasty, permitting optimal soft tissue preservation. Since Hueter first
      described this interval, many surgeons have approached the hip anteriorly to
      perform a myriad of surgical procedures. The anterior approach allows optimal
      muscle preservation, and it is a truly internervous approach to the hip. An
      understanding of the evolution of the anterior approach to the hip will help the
      orthopedic community understand these advantages and why so many have used this
      approach in the treatment of hip pathology and for the implantation total hip
      arthroplasty.

PMID- 19576400
TI  - Outcomes following the single-incision anterior approach to total hip
      arthroplasty: a multicenter observational study.
AB  - The authors conducted a retrospective, multicenter cohort study of 1,152 patients
      across nine clinical sites across the United States, evaluating complications and
      function associated with the anterior approach to total hip arthroplasty using an
      orthopedic table. Eligible patients included those with primary diagnosis of hip
      arthritis. Outcomes included hospital stay, use of assistive devices,
      complications, and function. In the cohort of 1,152 patients treated with the
      anterior approach to total hip arthroplasty, the authors found (i) an acceptable
      complication profile with a very low dislocation rate, (ii) an early return to
      function, and (iii) a decline in complications in surgeons with greater than 100
      case experiences.

PMID- 19576399
TI  - Direct anterior approach for total hip arthroplasty.
AB  - This article describes the surgical technique for total hip arthroplasty using
      the single-incision direct anterior approach. The authors believe the direct
      anterior approach has significant advantages, including minimal soft tissue
      trauma, resulting in faster postoperative mobilization and rehabilitation. The
      small incision scar also results in better cosmesis.

PMID- 19576401
TI  - Anterior-supine minimally invasive total hip arthroplasty: defining the learning
      curve.
AB  - The anterior-supine intermuscular approach is a truly muscle-sparing approach to
      total hip arthroplasty with a low complication rate. The advantages include
      improved early recovery and return to everyday activities. The authors found the
      learning curve to be around 40 cases and 6 months in a high-volume joint
      surgeon's practice. This article provides a detailed description of the surgical
      approach, including the use of a standard operating room table and fluoroscopy.
      Cadaver dissections and one-on-one mentoring are recommended when implementing
      this approach in one's practice.

PMID- 19576403
TI  - Hueter anterior approach for hip resurfacing: assessment of the learning curve.
AB  - The results of metal-on-metal hip resurfacing arthroplasty have been very
      encouraging. However, extensile approaches such as the posterior have been
      recommended to ensure proper component placement. This article evaluates the
      safety and the learning curve with the less invasive Hueter hip resurfacing using
      an anterior approach on an orthopedic traction table. The first 50 hip
      resurfacings using this approach are compared with the previous 50 procedures
      performed through a surgical dislocation approach. The authors conclude that it
      is a reasonable alternative to more extensile surgical approaches for a high
      volume resurfacing arthroplasty surgeon. Further long-term studies and
      comparisons to other approaches will determine if the anterior approach provides
      advantages in terms of patient function and time to recovery.

PMID- 19576402
TI  - Simultaneous bilateral supine anterior approach total hip arthroplasty:
      evaluation of early complications and short-term rehabilitation.
AB  - Simultaneous bilateral anterior approach total hip arthroplasty has been a
      successful procedure with high patient demand and good short-term clinical
      results. Complication rates are acceptable and compare favorably with previously
      published series. The anterior approach takes advantage of supine positioning,
      allowing improved intraoperative monitoring and anesthesia care. Short-term
      rehabilitation goals are met early with this technique. Despite these advantages,
      providing this simultaneous approach imposes a large financial burden on the
      hospital and surgeon.

PMID- 19576404
TI  - Comparison of mini-incision total hip arthroplasty through an anterior approach
      and a posterior approach using navigation.
AB  - This study reports on differences in the use of minimally invasive surgery for
      total hip arthroplasty related to the direction of cup insertion against the
      operating table, intraoperative hip range of motion, stability, and a choice of
      cup liners for both a mini-incision posterior approach (MPA) and a mini-incision
      anterior approach (MAA) using Stryker Navigation's CT-Hip system. The MPA group
      consisted of 39 consecutive patients and the MAA group consisted of 33
      consecutive patients. Clinically, there was no significant difference in the
      average Japanese Orthopedic Association hip score or the Oxford hip score
      preoperatively and at 6 months and 2 years follow-up. The intraoperative joint
      stability measurements showed no large difference between the two groups when
      malpositioning of the cup was eliminated.

PMID- 19576405
TI  - Complications of the direct anterior approach for total hip arthroplasty.
AB  - With the direct anterior approach gaining in popularity, it is important to
      appreciate the complications that are specific to it. The authors outline these
      potential complications and offer advice on the ways and the techniques to avoid
      them. This information is especially useful to the surgeon considering using this
      approach for the first time or to the surgeon who may already have encountered
      some of these complications as a result of using this approach.

PMID- 19576406
TI  - Multimodal analgesia for hip arthroplasty.
AB  - Multimodal analgesia incorporates the use of analgesic adjuncts with different
      mechanisms of action to enhance postoperative pain management. Acetaminophen,
      anti-inflammatories, and gabapentinoids provide effective analgesia while
      reducing opioid requirements and opioid-related side effects. Intrathecal
      morphine and periarticular local anesthetic infiltration further enhance dynamic
      analgesia and improve postoperative mobilization. Epidural analgesia, peripheral
      nerve blocks, tramadol, ketamine, and/or clonidine can be added for improved
      benefit in opioid-tolerant individuals.

PMID- 19576407
TI  - Anterior Hueter approach in the treatment of femoro-acetabular impingement:
      rationale and technique.
AB  - In the last decade, femoro-acetabular impingement (FAI) has been recognized as a
      cause of pain and early arthrosis in the young adult hip. Carl Hueter first
      described the anterior approach in 1881. This article discusses the indications
      and diagnostic criteria and the surgical technique and early clinical results for
      the combined arthroscopic/Hueter approach.

PMID- 19576408
TI  - Gait and motion analysis of the lower extremity after total hip arthroplasty:
      what the orthopedic surgeon should know.
AB  - This article presents critical issues related to the interpretation of
      biomechanical findings of the hip joint for patients having undergone hip
      arthroplasty. The use of a gait, or biomechanical, analysis provides objective
      evidence of the efficiency of the treatments or the effectiveness of hip
      replacement approaches. Based on our biomechanical analysis, patients who have
      undergone total hip arthroplasty use a stair ascent and descent strategy allowing
      them to significantly reduce loading at the prosthetic hip joint. Since hip joint
      reaction forces are highly dependent on muscle activation, the THA group have
      adopted a neuromuscular control strategy that is enabling them to reduce loading
      on the prosthetic hip joint. It could also be a joint loading pattern that stems
      from a muscular deficiency emerging either from several years of loading
      avoidance on the affected hip joint or from the surgical procedure. Therefore, a
      biomechanical analysis of human motion is a valuable tool for the orthopedic
      surgeon to objectively quantify joint motion and the forces producing this
      motion.

PMID- 19576409
TI  - Spatiotemporal parameters of gait after total hip replacement: anterior versus
      posterior approach.
AB  - The objective of this preliminary study was to examine possible differences in
      gait characteristics between subjects operated by way of a direct anterior
      approach and a posterior approach for primary total-hip arthroplasty, and age
      matched healthy controls. Fifty-one subjects walked over an instrumented mat at
      two different speeds (self-selected comfortable and faster than normal) and
      spatiotemporal gait parameters were calculated using a validated methodology.
      Despite excellent clinical and radiographic scores, and irrespective of surgical
      approach, patients demonstrated an impaired walking performance (lower velocity
      and shorter step lengths) during fast walking, but not at the self-selected
      comfortable speed compared with healthy controls. Subjects operated with the
      posterior approach reported significantly higher stiffness than anterior
      subjects, but similar pain and function. Six months after total arthroplasty for
      primary osteoarthritis of the hip, gait characteristics were comparable between
      subjects having received the direct anterior approach and the posterior approach.

PMID- 19576410
TI  - Blood management for hip reconstruction surgery.
AB  - Blood conservation techniques are well established and have significant benefits.
      We review the current literature on these techniques and their applicability to
      hip reconstruction surgery and offer a suitable strategy to minimize allogeneic
      red cell transfusion.

PMID- 19576411
TI  - Overview of current venous thromboembolism protocols in hip reconstruction.
AB  - Venous thromboembolic disease continues to be a serious complication of total-hip
      arthroplasty. The use of anticoagulant drugs for preventing this complication has
      repeatedly been proven to be useful. This article reviews the current evidence
      based recommendations for anticoagulant prophylaxis after total-hip arthroplasty
      and provides insight into the current areas of active research and controversy.

PMID- 19576412
TI  - Simultaneously fluorescence detecting thrombin and lysozyme based on magnetic
      nanoparticle condensation.
AB  - In this protocol, a fluorescent aptasensor based on magnetic separation for
      simultaneous detection thrombin and lysozyme was proposed. Firstly, one of the
      anti-thrombin aptamer and the anti-lysozyme aptamer were individually immobilized
      onto magnetic nanoparticles, acting as the protein captor. The other anti
      thrombin aptamer was labeled with rhodamine B and the anti-lysozyme aptamer was
      labeled with fluorescein, employing as the protein report. By applying the
      sandwich detection strategy, the fluorescence response at 515 nm and 578 nm were
      respectively corresponding to lysozyme and thrombin with high selectivity and
      sensitivities. The fluorescence intensity was individually linear with the
      concentration of thrombin and lysozyme in the range of 0.13-4 nM and 0.56-12.3
      nM, and the detection limits were 0.06 nM of thrombin and 0.2 nM of lysozyme,
      respectively. The preliminary study on simultaneous detection of thrombin and
      lysozyme in real plasma samples was also performed. It shows that the proposed
      approach has the good character for simultaneous multiple protein detection.

PMID- 19576413
TI  - Type I collagen-mediated synthesis of noble metallic nanoparticles networks and
      the applications in Surface-Enhanced Raman Scattering and electrochemistry.
AB  - In this paper, we demonstrated an effective environmentally friendly synthesis
      route to prepare noble metallic (Au, Ag, Pt and Pd) nanoparticles (NPs) networks
      mediated by type I collagen in the absence of any seeds or surfactants. In the
      reactions, type I collagen served as stabilizing agent and assembly template for
      the synthesized metallic NPs. The hydrophobic interaction between collagen and
      mica interface as well as the hydrogen bonds between inter- and intra-collagen
      molecules play important roles in the formation of collagen-metallic NPs
      networks. The noble metallic NPs networks have many advantages in the
      applications of Surface-Enhanced Raman Scattering (SERS) and electrochemistry
      detection. Typically, the as-prepared Ag NPs networks reveal great Raman
      enhancement activity for 4-ATP, and can even be used to detect low concentration
      of DNA base, adenine, without any label step. Furthermore, the cyclic
      voltammograms showed Pt NPs networks have good electrocatalytic ability for the
      reduction of O(2).

PMID- 19576414
TI  - Synthesis and photocatalytic applications of Ag/TiO2-nanotubes.
AB  - TiO2- and Ag/TiO2-nanotubes (NTs) were synthesized by hydrothermal methods and
      microwave-assisted preparation, respectively. Scanning electron microscopy, high
      resolution transmission electron microscopy, Brunauer-Emmett-Teller particle
      surface area measurement and X-ray diffraction were used to characterize the
      nanotubes. Rutile TiO2-NTs with Na(2)Ti(5)O(11) crystallinity had a length range
      of 200-400 nm and diameters of 10-20 nm. TiO2- and Ag/TiO2-NTs with a 0.4%
      deposition of Ag had high surface areas of 270 and 169 m(2)g(-1), respectively.
      The evaluation of photocatalytic activity showed that Ag/TiO2-NTs displayed
      higher photocatalytic activity than pure TiO2-NTs and a 60.91% degradation of
      Rhodamine-B with 0.8% deposition of Ag species. Also 60% of Rhodamine-6G was
      physisorbed and 40% chemisorbed on the surface of TiO2-NTs. In addition, the
      photocatalytic degradations of organochlorine pesticides taking alpha
      hexachlorobenzene (BHC) and dicofol as typical examples, were compared using
      Ag/TiO2-NTs, and found that their degradations rates were all higher than those
      obtained from commercial TiO2.

PMID- 19576415
TI  - Improvement of extraction capability of magnetic molecularly imprinted polymer
      beads in aqueous media via dual-phase solvent system.
AB  - In this study, a novel and simple dual-phase solvent system for the improvement
      of extraction capability of magnetic molecularly imprinted polymer (MIP) beads in
      aqueous sample was proposed. The method integrated MIP extraction and micro
      liquid-liquid extraction (micro-LLE) into only one step. A magnetic MIP beads
      using atrazine as template was synthesized, and was applied to aqueous media by
      adding micro-volume of n-hexane to form a co-extraction system. The magnetic MIP
      beads preferred to suspend in the organic phase, which shielded them from the
      disturbance of water molecule. The target analytes in the water sample was
      extracted into the organic phase by micro-LLE and then further bound to the solid
      phase of magnetic MIP beads. The beads specificity was significantly improved
      with the imprinting efficiency of template increasing from 0.5 to 4.4, as
      compared with that in pure aqueous media. The extraction capacity, equilibration
      process and cross-selectivity of the MIP dual-phase solvent extraction system
      were investigated. The proposed method coupled with high-performance liquid
      chromatography was applied to the analysis of atrazine, simazine, propazine,
      simetryn, prometryne, ametryn and terbutryn in complicated sample such as tomato,
      strawberry juice and milk. The method is selective, sensitive and low organic
      solvent-consuming, and has potential to broaden the range of MIP application in
      biological and environmental sample.

PMID- 19576416
TI  - Dual purpose laser ablation-inductively coupled plasma mass spectrometry for
      pulsed laser deposition and diagnostics of thin film fabrication: preliminary
      study.
AB  - PLD (pulsed laser deposition) is an attractive technique to fabricate thin films
      with a stoichiometry reflecting that of the target material. Conventional PLD
      instruments are more or less black boxes in which PLD is performed virtually
      "blind", i.e. without having great control on the important PLD parameters. In
      this preliminary study, for the first time, a 213 nm Nd-YAG commercial laser
      ablation-inductively coupled plasma mass spectrometer (LA-ICPMS) intended for
      microanalysis work was used for PLD under atmospheric pressure and in and ex situ
      ICPMS analysis for diagnostics of the thin film fabrication process. A PLD
      demonstration experiment in a He atmosphere was performed with a
      Sm(13.8)Fe(82.2)Ta(4.0) target-Ta-coated silicon wafer substrate (contraption
      with defined geometry in the laser ablation chamber) to transfer the permanent
      magnetic properties of the target to the film. Although this paper is not dealing
      with the magnetic properties of the film, elemental analysis was applied as a
      means of depicting the PLD process. It was shown that in situ ICPMS monitoring of
      the ablation plume as a function of the laser fluence, beam diameter and
      repetition rate may be used to ensure the absence of large particles (normally
      having a stoichiometry somewhat different from the target). Furthermore, ex situ
      microanalysis of the deposited particles on the substrate, using the LA-ICPMS as
      an elemental mapping tool, allowed for the investigation of PLD parameters
      critical in the fabrication of a thin film with appropriate density, homogeneity
      and stoichiometry.

PMID- 19576417
TI  - Ionic liquids as mobile phase additives in high-performance liquid chromatography
      with electrochemical detection: application to the determination of heterocyclic
      aromatic amines in meat-based infant foods.
AB  - The beneficial effects of several ionic liquids (ILs) as mobile phase additives
      in high-performance liquid chromatography with electrochemical detection for the
      determination of six heterocyclic aromatic amines (HAs) have been evaluated for
      first-time. The studied ionic liquids were 1-butyl-3-methylimidazolium
      tetrafluoroborate (BMIm-BF(4)), 1-hexyl-3-methylimidazolium tetrafluoroborate
      (HMIm-BF(4)) and 1-methyl-3-octylimidazolium tetrafluoroborate (MOIm-BF(4)).
      Several chromatographic parameters have been evaluated in the presence or absence
      of ILs, or using ammonium acetate as the most common mobile phase additive, with
      three different C18 stationary phases. The effect of the acetonitrile content was
      also addressed. In general, best resolution, lower peak-widths (up to 72.1%
      lower) and lower retention factors are obtained when using ILs rather than
      ammonium acetate as mobile phase additives. The main improvement was obtained in
      the baseline noise, being 360% less noisy for BMIm-BF(4), 310% for HMIm-BF(4),
      and 227% for MOIm-BF(4), when compared to ammonium acetate at +1000 mV. Different
      chromatographic methods using the best conditions for each IL were also evaluated
      and compared. Finally, the best chromatographic conditions using 1mM of BMIm
      BF(4) as mobile phase additive, the Nova-Pak C18 column, 19% (v/v) of
      acetonitrile content in the mobile phase, and +1000 mV in the ECD, have been
      applied for the chromatographic analysis of six HAs contained in meat-based
      infant foods. The whole extraction method of meat-based infant foods using
      focused microwave-assisted extraction and solid-phase extraction has also been
      optimized. Extraction efficiencies up to 89% and detection limits ranged between
      9.30 and 0.165 ng g(-1) have been obtained under optimized conditions.

PMID- 19576418
TI  - Pressurized liquid extraction followed by gas chromatography with atomic emission
      detection for the determination of fenbutatin oxide in soil samples.
AB  - A novel method for the determination of the miticide bis[tris(2-methyl-2
      phenylpropyl)tin] oxide, also known as fenbutatin oxide (FBTO), in agricultural
      soils is presented. Pressurized liquid extraction (PLE) followed by analyte
      derivatization and extraction into isooctane was the used sample preparation
      approach. Selective determination was achieved by gas chromatography with atomic
      emission detection (GC-AED). Influence of different parameters on the performance
      of the extraction process is thoroughly discussed; moreover, some relevant
      aspects related to derivatization, determination and quantification steps are
      also presented. As regards PLE, the type of solvent and the temperature were the
      most relevant variables. Under optimized conditions, acetone, without any acidic
      modifier, was employed as extractant at 80 degrees C. Cells were pressurized at
      1500 psi, and 2 static cycles of 1 min each were applied. Acetone extracts (ca.
      25 mL) were concentrated to 1 mL, derivatized with sodium tetraethyl borate
      (NaBEt(4)) and the FBTO derivative, resulting from cleavage of the Sn-O-Sn bond
      followed by ethylation of the hydroxyl fragments, extracted into isooctane and
      determined by GC-AED. Under final working conditions, the proposed method
      provided recoveries from 76 to 99% for spiked soil samples, a limit of
      quantification of 2 ng g(-1) and an acceptable precision. Analysis of samples
      from vineyards sprayed with FBTO, confirmed the persistence of the miticide in
      soil for more than 1 year after being applied.

PMID- 19576419
TI  - Usage of Empore membrane in alcoholic media for copper(II) distribution studies.
AB  - The sorption of copper(II) on a solid, iminodiacetic based, chelating material,
      the Empore membrane, in alcoholic solutions is considered. Determination of the
      acid-base properties, kinetic of metal sorption and complexing properties, in
      solutions with different percentages of ethanol, ranging from 0 to 40% is
      undertaken. The results are compared with those obtained using the classical
      iminodiacetic resin Chelex 100 in beads. No significant differences are found in
      the thermodynamic properties, but the kinetics of the metal sorption on the
      membrane is slower and a dependence of the process rate with the alcoholic
      content is observed. In the present investigation, the detection of copper(II)
      species both in alcoholic Italian distillate "grappa" and in its intermediate
      product ("flemma"), is carried out by the Resin Titration (RT) method using, as
      competitive reagent, the Empore membrane. To validate the procedure, synthetic
      solutions containing different percentages of ethanol are analysed.

PMID- 19576420
TI  - Comparison of several solid-phase extraction sorbents for continuous
      determination of amines in water by gas chromatography-mass spectrometry.
AB  - A semiautomatic method has been proposed for the determination of different types
      of amines in water samples including anilines, chloroanilines, N-nitrosamines and
      aliphatic amines. The analytes were retained on a solid-phase extraction sorbent
      column and after elution, 1 microL of the extract was analysed by gas
      chromatography coupled with electron impact ionization mass spectrometry. A
      systematic overview is given of the advantages and disadvantages of several
      sorbents (LiChrolut EN, Oasis HLB, RP-C(18), graphitized carbon black, fullerenes
      and nanotubes) in the retention of amine compounds and based on sensitivity,
      selectivity and reliability. The retention efficiency for the studied amines was
      higher (ca. 100%) with LiChrolut EN and Oasis HLB than it was with RP-C(18) and
      fullerenes (53 and 62%, respectively, on average). Detection limits of 0.5-16 ng
      L(-1) for the 27 amines studied were obtained when using a sorbent column
      containing 75 mg of LiChrolut EN for 100mL of sample, the RSD being lower than
      6.5%. The method was applied with good accuracy and precision in the
      determination of amines in various types of water including river, pond, tap,
      well, drinking, swimming pool and waste.

PMID- 19576422
TI  - Development of a rapid and automatic optosensor for the determination of cromolyn
      in biological samples.
AB  - Disodium cromoglycate (SCG) is an anti-allergic drug, which is applied locally or
      inhaled. After administration, a very small portion of the drug is absorbed,
      being the most eliminated part unchanged in the urine and bile; therefore, its
      determination in urine is indicative of the dose absorbed. Here, the first
      spectroscopic method for the determination of SCG, making use of a sequential
      injection optosensor with terbium-sensitized luminescence detection, is
      described. The cationic resin Chelex-100 was used as solid support in the
      detection area. The measurements were made at 336/545 nm (lambda(ex)/lambda(em))
      and the system was calibrated for two sample volumes, 150 and 800 microl,
      depending on the samples analyzed. A detection limit of 15 ng ml(-1) and a RSD
      lower than 2% (n=10) were observed using the highest sample volume. The proposed
      method does not use any organic solvent or surfactant, so being environmental
      friendly. The analyte was satisfactorily determined in pharmaceuticals and human
      urine, the latter being spiked at the concentrations found after the
      administration of the drug.

PMID- 19576421
TI  - Liquid-waveguide spectrophotometric measurement of low silicate in natural
      waters.
AB  - This paper describes a robust, sensitive method for measurement of low silicate
      in natural water. The method is based on the reaction of silicate with ammonium
      molybdate to form a yellow silicomolybdate complex, which is then reduced to
      silicomolybdenum blue by ascorbic acid. This method shows no refractive index
      effect and a small salinity effect that can be corrected for seawater samples. It
      was found that the use of poly-vinyl alcohol can prevent the precipitation
      formation in the ammonium molybdate solution and improve the stability of the
      silicomolybdenum blue complex. The sensitivity of this method is substantially
      enhanced by using a liquid-waveguide capillary cell. The detection limit is 0.1
      microM, and working range is 0.1-10 microM for using 2-m liquid-waveguide
      capillary cell (LWCC). The method can be used for both freshwater and seawater
      samples and has been used to study the distribution of silicate in surface
      seawater of Gulf Stream in Florida straight.

PMID- 19576423
TI  - Dynamic hollow-fibre liquid phase microextraction of dinitrophenols from human
      plasma: optimization of an extraction flow system using experimental design
      methodology.
AB  - The utility of a dynamic hollow-fibre liquid phase microextraction method
      (optimized using a four-variable experimental design and response surface
      modelling) for extracting dinitrophenolic compounds from human plasma samples was
      evaluated. The investigated variables were donor phase salt concentration (10-400
      mM), donor phase pH (2-6), acceptor phase pH (7-12), and donor/acceptor phase
      flow rates (30/7.5 to 70/17.5 microL min(-1)). Four dinitrophenol pesticides were
      used as model substances at concentrations of 0.1 microg mL(-1) in spiked human
      plasma samples. Extraction efficiencies ranging from 42 to 77% with RSDs below 9
      were achieved with the optimized method. The flow rate and acceptor pH were shown
      to strongly affect the extraction efficiency for all compounds, while the donor
      phase pH and salt concentration had minor effects. With a well-defined acceptor
      phase pH and flow rate the system exhibited high robustness. The limits of
      quantification for the investigated compounds, using the presented extraction
      method followed by liquid chromatography/electrospray ionization mass
      spectrometry in selected ion monitoring mode, ranged from 0.05 to 0.1 microg mL(
      1) plasma.

PMID- 19576425
TI  - Second-order calibration of excitation-emission matrix fluorescence spectra for
      determination of glutathione in human plasma.
AB  - A rapid non-separative spectroflourimetric method based on the second-order
      calibration of the excitation-emission data matrix was proposed for the
      determination of glutathione (GSH) in human plasma. In the phosphate buffer
      solution of pH 8.0 GSH reacts with ortho-phthaldehyde (OPA) to yield a
      fluorescent adduct with maximum fluorescence intensity at about 420 nm. To handle
      the interfering effects of the OPA adducts with aminothiols other than GSH in
      plasma as well as intrinsic fluorescence of human plasma, parallel factor
      (PARAFAC) analysis as an efficient three-way calibration method was employed. In
      addition, to model the indirect interfering effect of the plasma matrix, PARAFAC
      was coupled with standard addition method. The two-component PARAFAC modeling of
      the excitation-emission matrix fluorescence spectra accurately resolved the
      excitation and emission spectra of GSH, plasma (or plasma constituents). The
      concentration-related PARAFAC score of GSH represented a linear correlation with
      the concentration of added GSH, similar to that is obtained in simple standard
      addition method. Using this standard addition curve, the GSH level in plasma was
      found to be 6.10+/-1.37 micromol L(-1). The accuracy of the method was
      investigated by analysis of the plasma samples spiked with 1.0 micromol L(-1) of
      GSH and a recovery of 97.5% was obtained.

PMID- 19576424
TI  - Poly(3-methylthiophene)/palladium sub-micro-modified sensor electrode. Part II:
      Voltammetric and EIS studies, and analysis of catecholamine neurotransmitters,
      ascorbic acid and acetaminophen.
AB  - Promising voltammetric sensors based on the modification of Pt and poly(3
      methylthiophene) (PMT) electrodes with Pd nanoparticles were achieved for the
      determination of catecholamine neurotransmitters, ascorbic acid and
      acetaminophen. Electrochemistry of the indicated compounds was studied at these
      electrodes and interesting electrocatalytic effects were found. Furthermore,
      simple, easily prepared one electrochemical step Pd-modified Pt electrode (Pt/Pd)
      is reported for the first time. Cyclic voltammetry (CV) and chronocoulometry (CC)
      were used for the determination of the apparent diffusion coefficients in
      different electrolytes at these electrodes and the values are in the range from
      10(-4) to 10(-5)cm(2)s(-1). Furthermore, it was found that the method of polymer
      formation had a substantial effect on the synergism between the polymer film and
      the loaded metal particles towards the oxidation of dopamine (DA) in different
      supporting electrolytes. This was confirmed by the CV, CC and EIS
      (electrochemical impedance spectroscopy) as well as SEM (Scanning Electron
      Microscopy) results. Pt and PMT electrodes modified with Pd nanoparticles showed
      excellent results for the simultaneous determination of tertiary and quaternary
      mixtures of the studied compounds.

PMID- 19576427
TI  - Chaotic parameters and their role in quantifying noise in the output signals from
      UV, TGA and DSC apparatus.
AB  - Two fractal dimensions and the Liapunov exponent (LE) have been applied to detect
      noisy output signals from UV spectrophotometer (UV), thermogravimetric analyzer
      (TGA) and differential scanning calorimeter (DSC) apparatus of 1-ethyl-3
      methylimidazolium ethylsulfate ionic liquid ([emim][EtSO(4)]). The data collected
      from these three pieces of equipment were classified before calculating LE,
      regularization (RD) and box dimensions (BD). The RD and LE are able individually
      to detect and quantify noisy output signals with a mean error value less than 5%
      in all cases tested. Given that the LE can be calculated using a really simple
      method, this chaotic parameter has been selected as the most suitable to detect
      noise of signals from these apparatus.

PMID- 19576426
TI  - Implementation of enhanced correlation maps in near infrared chemical images:
      application in pharmaceutical research.
AB  - Recent developments in Hyperspectral Imaging equipment have made possible the use
      of this analytical technique for fast scanning of sample surfaces. This technique
      has turned out to be especially useful in Pharmacy, where information about the
      distribution of the components in the surface of a tablet can be obtained. One
      particular application of Hyperspectral Chemical Imaging is the search for
      singularities inside pharmaceutical tablets, e.g. coating defects. Nevertheless,
      one problem has to be faced: how to analyze a sample without any previous
      knowledge about it, or having only the minimum information about the tablet. In
      this work a new methodology, based on correlation coefficients, is introduced to
      obtain valuable information about one Hyperspectral Image (detection of defects,
      punctual contaminants, etc.) without any previous knowledge. The methodology
      combines Principal Component Analysis (PCA), correlation coefficient between one
      specific pixel included in the image and the rest of the image; and a new
      enhanced contrast function to obtain more selective chemical and spatial
      information about the image. To illustrate the applicability of the proposed
      methodology, real tablets of ibuprofen have been studied. The proposed
      methodology is presented as a control technique to detect batch variability,
      defects in final tablets and punctual contaminants, being a potential
      supplementary tool for quality controls. In addition, the usefulness of the
      proposed methodology is not exclusive to NIR-CI devices, but to any hyperspectral
      and multivariate image system.

PMID- 19576428
TI  - Selective separation and determination of primidone in pharmaceutical and human
      serum samples using molecular imprinted polymer-electrospray ionization ion
      mobility spectrometry (MIP-ESI-IMS).
AB  - Application of electrospray ionization ion mobility spectrometry (ESI-IMS) as the
      detection technique for separation method based on molecular imprinted polymer
      (MIP) was investigated and evaluated. The method is exhaustively validated,
      including sensitivity, selectivity, recovery, reproducibility, and column
      capacity. The linear dynamic range of 0.02-2.00 microg mL(-1) was obtained for
      primidone analysis with ESI-IMS. The recovery of drug analyzed was calculated to
      be above 90% and the relative standard deviation (RSD), was below 3% for all
      experiments. Various real samples were analyzed with the coupled techniques, and
      the results obtained revealed the efficient clean-up of the samples using MIP
      separation before the analysis by ESI-IMS as a detection technique.

PMID- 19576429
TI  - Determination of naproxen in human urine by high-performance liquid
      chromatography with direct electrogenerated chemiluminescence detection.
AB  - A simple and sensitive liquid chromatographic method coupled with
      electrogenerated chemiluminescence (ECL) was described for the separation and
      quantification of naproxen in human urine. The method was based on the ECL of
      naproxen in basic NaNO(3) solution with a dual-electrode system. Factors affected
      the ECL emission were investigated. Under the optimal conditions, the ECL
      intensity has a linear relationship with the concentration of naproxen in the
      range of 4.0 x 10(-8)g mL(-1) to 2.0 x 10(-6)g mL(-1) and the detection limit was
      1.6 x 10(-8)g mL(-1) (S/N=3). Application of the method to the analyses of
      naproxen in human urine proved feasible.

PMID- 19576430
TI  - Screen-printed immunosensor modified with carbon nanotubes in a continuous-flow
      system for the Botrytis cinerea determination in apple tissues.
AB  - Botrytis cinerea is a plant-pathogenic fungus that produces the disease known as
      grey mould in a wide variety of agriculturally important hosts in many countries.
      This paper describes the development of an immunosensor coupled to carbon-based
      screen-printed electrodes (SPCE) modified with multi-walled carbon nanotubes
      (CNTs), which show a rapid and sensitive determination of B. cinerea in apple
      tissues (Red-delicious) using a competitive immunoassay method. Both the infected
      plant tissue sample and the B. cinerea-specific monoclonal antibody are allowed
      to react immunologically with the B. cinerea purified antigens immobilized on a
      rotating disk. Then, the bound antibodies are quantified by a horseradish
      peroxidise (HRP) enzyme labeled second antibodies specific to mouse IgG, using 4
      tertbutylcatechol (4-TBC) as enzymatic mediators. The HRP, in the presence of
      hydrogen peroxide, catalyses the oxidation of 4-TBC to 4-tertbutyl o
      benzoquinone. The electrochemical reduction back to 4-TBC is detected on SPCE-CNT
      at -0.15 V. The response current is inversely proportional to the amount of the
      B. cinerea antigens present in the fruit sample. The time consumed per assay was
      30 min and the calculated detection limits for electrochemical method and the
      ELISA procedure are 0.02 and 10 microg mL(-1), respectively. Moreover the intra-
      and inter-assay coefficients of variation were below 7%. This electrochemical
      immunosensor promises to be usefully suited to the detection and quantification
      of B. cinerea in apparently healthy plant prior to the development of the
      symptoms.

PMID- 19576431
TI  - Electrochemical study and analytical applications for new biologically active 2
      nitrophenylbenzimidazole derivatives.
AB  - The present study addresses the electrochemical behavior and the analytical
      applications of six 2-nitrophenylbenzimidazole derivatives with activity against
      Trypanosoma cruzi. When studied in a wide range of pH, by differential pulse
      polarography, tast polarography and cyclic voltammetry, these compounds exhibited
      two irreversible cathodic responses. With analytical purposes, the differential
      pulse polarography mode was selected, which exhibited adequate analytical
      parameters of repeatability, reproducibility and selectivity. The percentage of
      recovery was in all cases over 99%, and the detection and quantitation limits
      were at the level of 1 x 10(-7)mol L(-1) and 1 x 10(-6)mol L(-1), respectively.
      In addition, the differential pulse polarography method was successfully applied
      to study the hydrolytic degradation kinetic of one of the tested compounds.
      Activation energy, kinetic rate constants at different temperatures and half-life
      values of such application are reported.

PMID- 19576432
TI  - Multivariate optimization of hydrodistillation-headspace solvent microextraction
      of thymol and carvacrol from Thymus transcaspicus.
AB  - In this paper multivariate response surface methodology (RSM) has been used for
      the optimization of hydrodistillation-headspace solvent microextraction (HD-HSME)
      of thymol and carvacrol in Thymus transcaspicus. Quantitative determination of
      compounds of interest was performed simultaneously using gas chromatography
      coupled with flame ionization detector (GC-FID). Parameters affecting the
      extraction efficiency were assessed and the optimized values were 5 min, 2 microL
      and 3 min for the extraction time, micro-drop volume and cooling time after
      extraction, respectively. The amounts of analyte extracted increased with plant
      weight. The calibration curves were linear in the ranges of 6.25-81.25 and 1.25
      87.50 mg L(-1) for thymol and carvacrol, respectively. Limit of detection (LOD)
      for thymol and carvacrol was 1.87 and 0.23 mg L(-1), respectively. Within-day and
      between-day precisions for both analytes were calculated in three different
      concentrations and recoveries obtained were in the range of 89-101% and 95-116%
      for thymol and carvacrol, respectively.

PMID- 19576433
TI  - Facile detection of proteins on a solid-phase membrane by direct binding of
      dextran-based luminol-biotin chemiluminescent polymer.
AB  - Facile and non-radioactive methods are desired for the sensitive detection and
      quantification of various proteins. Herein we describe a novel chemiluminescence
      (CL)-detection method of particular proteins based on direct binding of a dextran
      luminol-biotin (DLB) CL polymer to the proteins on a poly(vinylidene difluoride)
      membrane. Among 32 kinds of the proteins screened, several proteins such as drug
      metabolizing enzymes, cytochrome p450 (CYP)1A2, CYP2E1, and CYP3A4 had the
      ability to bind directly to the DLB polymer. The binding site in the polymer was
      owing to the framework of the modified dextran, which underwent oxidation and
      reduction procedures. This interaction might be the comprehensive effect of both
      electrostatic interaction and steric complementarities. CL intensity of the
      proteins detected by the polymer could be further enlarged by the mediation of
      avidin. The proposed CL-imaging method possesses potential as a rapid, facile,
      inexpensive and selective detection of the proteins.

PMID- 19576434
TI  - Analytical speciation of mercury in fish tissues by reversed phase liquid
      chromatography-inductively coupled plasma mass spectrometry with Bi(3+) as
      internal standard.
AB  - In this work, the quantification of two mercury species (Hg(2+) and CH(3)Hg(+))
      in fish tissues has been revisited. The originality of our approach relies on the
      use of Bi(3+) as internal standard (IS) and on the modification of typical
      extraction conditions. The IS (125 microl, 1000 microg l(-1) Bi(3+)) was added to
      the aliquot of fresh fish tissue (400-500 mg). A high-speed blender and
      ultrasound-assisted homogenization/extraction was carried out in the presence of
      perchloric acid (1.5 ml, 0.6 mol l(-1)), l-cysteine (500 microl, 0.75 mol l(-1))
      and 500 microl toluene:methanol (1:1). Perchloric acid was used for protein
      denaturation and precipitation, toluene helped to destroy lipid structures
      potentially sequestering CH(3)Hg(+), L-cysteine was used to form water-soluble
      complexes with Bi(3+), Hg(2+) and CH(3)Hg(+). The excess of perchloric acid was
      eliminated by addition of potassium hydroxide (pH 5 with acetic acid). The
      obtained extract, was diluted with the mobile phase (1:1) and introduced (20
      microl) to the reversed phase HPLC-ICP-MS system. The separation was achieved by
      isocratic elution (2.5 mmol l(-1) cysteine, 12.5 mmol l(-1) (NH(4))(2)HPO(4),
      0.05% triethylamine, pH 7.0:methanol (96:4)) at a flow rate 0.6 ml min(-1).
      Column effluent was on-line introduced to ICP-MS for specific detection of
      (202)Hg, (200)Hg and (209)Bi. Analytical signal was defined as the ratio between
      (202)Hg/(209)Bi peak areas. The detection limits evaluated for Hg(2+) and
      CH(3)Hg(+) were 0.8 and 0.7 microg l(-1). Recovery of the procedure, calculated
      as the sum of species concentrations found in the sample with respect to total
      ICP-MS-determined Hg was 91.9% for king mackerel muscle and 89.5% for red snapper
      liver. In the standard addition experiments, the recovery results were 98.9% for
      Hg(2+) and 100.6% for CH(3)Hg(+). It should be stressed that the use of Bi(3+) as
      IS enabled to improve analytical performance by compensating for incomplete
      extraction and for imprecision of sample handling during relatively non-rigorous
      protocol.

PMID- 19576435
TI  - Multi-residue analysis and ultra-trace quantification of 36 priority substances
      from the European Water Framework Directive by GC-MS and LC-FLD-MS/MS in surface
      waters.
AB  - A multi residue analysis was developed for screening, quantification and
      confirmation of 36 priority organic compounds included in the 2000/60/EC European
      Water Framework Directive. The compounds analyzed included 19 pesticides, 8 PAH,
      5 endocrine-disruptors and 4 organochlorine compounds. The method was developed
      in three steps. First, automated off-line solid-phase extraction using Strata X
      cartridges was optimized to trap simultaneously the 36 studied compounds. Second,
      the more volatile compounds were analysed by gas chromatography coupled to mass
      spectrometry with electron impact ionisation in selected ion monitoring mode
      (SIM). Third, the last 20 compounds were detected and quantified, in one run, by
      liquid chromatography coupled to fluorescence detector and tandem mass
      spectrometry. The excellent selectivity and sensitivity allowed us satisfactory
      quantification and confirmation at levels as low as 0.2-67 ng L(-1) with
      recoveries between 59 and 105%. Such methodology was then applied to French
      surface waters: all the waters present organic contaminants, and their
      concentration varied according to the origin and nature of substances.

PMID- 19576436
TI  - Inductively coupled plasma-optical emission spectrometry/mass spectrometry for
      the determination of Cu, Ni, Pb and Zn in seawater after ionic imprinted polymer
      based solid phase extraction.
AB  - The capabilities of a synthesized ionic imprinted polymer (IIP), originally
      prepared for Ni recognition/pre-concentration from seawater, have been evaluated
      for other trace elements pre-concentration. The polymer has been synthesized by
      the precipitation polymerization technique using a ternary pre-polymerization
      complex formed by the template (Ni), the monomer (2-(diethylamino) ethyl
      methacrylate, DEM) and a non-vinylated chelating agent (8-hydroxyquinoline, 8
      HQ). Since the complexing agent (8-HQ) is trapped into the polymeric matrix, but
      is not linked to the polymer chains, specific interactions between the functional
      groups (present in the monomer and the complexing agent) and other trace elements
      rather than Ni may occur. Results have shown that the IIP offers imprinting
      properties for the template (Ni(II)) and also for Cu(II), Pb(II), Zn(II), As(V)
      and Cd(II), with analytical recoveries close to 100% for all elements except for
      As(V) and Cd(II) (around 70%), whereas the non-imprinted polymer (NIP) did not
      show affinity for any trace element. In addition, the polymer does not interact
      with alkaline or alkaline-earth metals, so Na, K, Mg and Ca from the seawater
      salt matrix could be effectively removed. Variables affecting the IIP-solid phase
      extraction (SPE) process (pH, load flow rate and concentration and volume of the
      eluting solution) were completely studied. Inductively coupled plasma-optical
      emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry
      (ICP-MS) have been used as multi-element detectors. Acidified seawater samples
      must only be treated to fix an alkaline pH (8.5+/-0.5) and passed through IIP-SPE
      cartridges. After seawater sample loading (250 mL), analytes were eluted with 2.5
      mL of 2.0M nitric acid, offering a pre-concentration factor of 100. Therefore,
      the limits of detection (LODs) of the method were 0.14, 0.15, 0.18 and 0.03
      microg L(-1), for Ni, Cu, Pb and Zn, respectively, when using ICP-OES detection
      and 0.0022, 0.0065, 0.0040 and 0.009 microg L(-1), for Ni, Cu, Pb and Zn,
      respectively, for ICP-MS detection. Accuracy of the method was assessed by
      analyzing SLEW-3 (estuarine water), and TM-23.3 and TM-24 (lake water) certified
      reference materials.

PMID- 19576437
TI  - A novel tris(2,2'-bipyridine)ruthenium(II)/tripropylamine cathodic
      electrochemiluminescence in acetonitrile for the indirect determination of
      hydrogen peroxide.
AB  - A novel tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)(3)(2+)) cathodic
      electrochemiluminescence (ECL) was generated at -0.78 V at the Pt electrode in
      acetonitrile (ACN), which suggested that the cathodic ECL differed from
      conventional cathodic ECL. It was found that tripropylamine (TPrA) could enhance
      this cathodic ECL and the linear range (log-log plot) was 0.2 microM-0.2mM. In
      addition, hydrogen peroxide (H(2)O(2)) could inhibit the cathodic ECL and was
      indirectly detected with the linear range of 27-540 microM. The RSD (n=12) of the
      ECL intensity in the presence of 135 microM H(2)O(2) was 0.87%. This method was
      also demonstrated for the fast determination of H(2)O(2) in disinfectant sample
      and satisfactory results were obtained.

PMID- 19576438
TI  - Speciation of selenomethionine and selenocystine using online micro-column
      containing Cu(II) loaded nanometer-sized Al2O3 coupled with ICP-MS detection.
AB  - A flow injection online speciation procedure by using micro-column packed with
      Cu(II) loaded nanometer-sized Al(2)O(3) coupled to inductively coupled plasma
      mass spectrometry (ICP-MS) for the separation and determination of
      selenomethionine (SeMet) and selenocystine (SeCys(2)) has been developed. The
      main factors affecting the separation and preconcentration of SeMet and SeCys(2)
      including pH value, sample flow rate, eluent concentration, eluent volume and
      flow rate, and interfering ions have been investigated. It was found that
      SeCys(2) could be selectively retained by micro-column packed with Cu(II) loaded
      nanometer-sized Al(2)O(3) at pH 4.0, and the retained SeCys(2) could be eluted by
      1.0 mol L(-1) HNO(3), while SeMet was not retained and passed through the micro
      column directly at this pH. Both SeMet and SeCys(2) could be quantitatively
      adsorbed by the micro-column at pH 9.0, and the retained SeMet and SeCys(2) could
      be easily eluted with 1.0 mol L(-1) HNO(3). The content of SeMet was obtained by
      subtracting the SeCys(2) from the total content of seleno amino acids. With the
      enrichment factor of 7.8 and 7.7, the limits of detection (LODs) for SeMet and
      SeCys(2) were found to be 24 pg Se mL(-1) and 21 pg Se mL(-1), respectively. The
      relative standard deviations (RSDs) for SeCys(2) and SeMet with seven replicate
      determinations of 1.0 ng mL(-1) SeMet and SeCys(2), were 2.1% and 1.6%,
      respectively, the sampling frequency of 8h(-1) was obtained. The proposed method
      was applied to the speciation of SeMet and SeCys(2) in selenized yeast, human
      urine and serum with satisfactory results.

PMID- 19576439
TI  - Preparation and characterization of monolithic column by grafting pH-responsive
      polymer.
AB  - A novel modified monolithic column with pH-responsive polymer chains was prepared
      by grafting methacrylic acid onto the poly(glycidyl methacrylate-co-ethylene
      dimethacrylate) monolith. The grafting polymerization was achieved in an in situ
      manner which was performed by pumping methacrylic acid directly through an acidic
      hydrolysis monolithic column using potassium peroxydisulfate initiated free
      radical polymerization. The grafted monolithic column was demonstrated to be the
      pH-responsive to the pore structure and the chromatographic characterization. The
      permeability of the column and the retention factors of five benzene homologues
      decreased due to the conformational changes of the polymer chains when the pH of
      mobile phase increased from 4.5 to 7.5. Furthermore, the modified monolithic
      column was used as the pH-responsive stationary phase and exhibited an excellent
      separation of four basic proteins.

PMID- 19576440
TI  - Electrochemically deposited boronate affinity extracting phase for covalent solid
      phase microextraction of cis-diol biomolecules.
AB  - A new format of solid phase microextraction (SPME), boronate affinity SPME, was
      proposed for the first time for covalent extraction of cis-diol containing
      biomolecules. This new SPME format is based on the reversible complex formation
      between boronic acids and 1,2- and 1,3-cis-diols. The complex formation and
      dissociation can be facilely controlled by changing pH. An extracting phase of
      poly-3-aminophenylboronate (polyAPBA) electrochemically deposited on a metal wire
      was employed to demonstrate the concept of this new methodology. Catechol and
      riboflavin were used as the test analytes, and the SPME extraction was combined
      off-line with high-performance liquid chromatographic (HPLC) separation followed
      by UV absorbance or fluorescence detection. Fundamental aspects, such as
      selectivity, extraction/desorption equilibrium, linearity, effect of competing
      compounds, reproducibility and life-time, were first investigated. Then the
      developed method was applied to beer samples since the content of riboflavin
      plays an important role in the flavor stability of beverages. Excellent
      performance of the SPME fibers was observed for both standard and real samples.
      Particularly, the expected excellent features of the polyAPBA extracting phase
      were experimentally verified, which include specific selectivity, eliminated
      matrix effect and manipulable capture/release. The new methodology of SPME can be
      a promising tool since a lot of 1,2- and 1,3-cis-diol-containing compounds are of
      great biological importance.

PMID- 19576441
TI  - Chromatographic retention prediction and octanol-water partition coefficient
      determination of monobasic weak acidic compounds in ion-suppression reversed
      phase liquid chromatography using acids as ion-suppressors.
AB  - Although simple acids, replacing buffers, have been widely applied to suppress
      the ionization of weakly ionizable acidic analytes in reversed-phase liquid
      chromatography (RPLC), none of the previously reported works focused on the
      systematic studies about the retention behavior of the acidic solutes in this ion
      suppression RPLC mode. The subject of this paper was therefore to investigate the
      retention behavior of monobasic weak acidic compounds using acetic, perchloric
      and phosphoric acids as the ion-suppressors. The apparent octanol-water partition
      coefficient (K" ow) was proposed to calibrate the octanol-water partition
      coefficient (K(ow)) of these weak acidic compounds, which resulted in a better
      linear correlation with log k(w), the logarithm of the hypothetical retention
      factor corresponding to neat aqueous fraction of hydroorganic mobile phase. This
      log K" ow-log k w linear correlation was successfully validated by the results of
      monocarboxylic acids and monohydrating phenols, and moreover by the results under
      diverse experimental conditions for the same solutes. This straightforward
      relationship not only can be used to effectively predict the retention values of
      weak acidic solutes combined with Snyder-Soczewinski equation, but also can offer
      a promising medium for directly measuring K(ow) data of these compounds via
      Collander equation. In addition, the influence of the different ion-suppressors
      on the retention of weak acidic compounds was also compared in this RPLC mode.

PMID- 19576442
TI  - Development and validation of a simple stability-indicating high performance
      liquid chromatographic method for the determination of miconazole nitrate in bulk
      and cream formulations.
AB  - A simple and stability-indicating high performance liquid chromatographic method
      was developed and validated for the determination of miconazole nitrate in bulk
      and cream preparations. The extraction step for cream samples consisted in a
      warming, cooling and centrifugation procedure that assures the elimination of the
      lipophilic matrix component, in order to avoid further precipitation in the
      chromatographic system. Separation was achieved on a ZORBAX Eclipse XDB - C18
      (4.6 mm x 150 mm, 5 microm particle size) column, using a mobile phase consisting
      of water, methanol and acetonitrile, in a flow and solvent gradient elution for
      15 min. The column was maintained at 25 degrees C and 10 microL of solutions were
      injected. UV detection was performed at 232 nm, although employment of a diode
      array detector allowed selectivity confirmation by peak purity evaluation. The
      method was validated reaching satisfactory results for selectivity, precision and
      accuracy. Degradation products in naturally aged samples could be simultaneously
      evaluated, without interferences in the quantitative analysis.

PMID- 19576443
TI  - Simultaneous voltammetric determination of prednisone and prednisolone in human
      body fluids.
AB  - A sensitive, rapid and reliable electrochemical method based on voltammetry at
      single wall carbon nanotube (SWNT) modified edge plane pyrolytic graphite
      electrode (EPPGE) is proposed for the simultaneous determination of prednisolone
      and prednisone in human body fluids and pharmaceutical preparations. The
      electrochemical response of both the drugs was evaluated by osteryoung square
      wave voltammetry (OSWV) in phosphate buffer medium of pH 7.2. The modified
      electrode exhibited good electrocatalytic properties towards prednisone and
      prednisolone reduction with a peak potential of approximately -1230 and
      approximately -1332 mV respectively. The concentration versus peak current plots
      were linear for both the analytes in the range 0.01-100 microM and the detection
      limit (3 sigma/slope) observed for prednisone and prednisolone were 0.45 x 10(
      8), 0.90 x 10(-8)M, respectively. The results of the quantitative estimation of
      prednisone and prednisolone in biological fluids were also compared with HPLC and
      the results were in good agreement.

PMID- 19576444
TI  - Highly sensitive fluorescent sensor for mercury ion based on photoinduced charge
      transfer between fluorophore and pi-stacked T-Hg(II)-T base pairs.
AB  - A novel and simple oligodeoxyribonucleotide-based sensor with single fluorophore
      labeled for mercury ion sensing was reported. An oligodeoxyribonucleotide
      poly(dT) was labeled with fluorescein as donor. Based on the specific binding of
      Hg(II) to T-T mismatch base pairs, the formation of pi-stacked [T-Hg(II)-T] with
      "sandwich" structure on the addition of Hg(II) ions facilitates the electron
      transfer via photoinduced charge transfer (PCT), which creates an additional
      nonradiative decay channel for excited fluorophore and triggers the fluorescence
      to be quenched. The pi-stacked [T-Hg(II)-T] functioned not only as mercury ion
      recognition but also as an electron acceptor to quench the donor. A linear
      relationship was observed over the range of 0-1.0 microM with the detection limit
      of 20 nM for mercury ions. The fluorescence quenching phenomenon and quenching
      mechanism, reliability and selectivity of the system were investigated in detail.

PMID- 19576445
TI  - Direct electrochemistry and electrocatalysis of hemoglobin immobilized in a
      magnetic nanoparticles-chitosan film.
AB  - Magnetic nanoparticles (Fe(3)O(4)) were synthesized by a chemical coprecipitation
      method. X-ray diffraction (XRD) and transmission electron microscope (TEM) were
      used to confirm the crystallite structure and the particle's radius. The
      Fe(3)O(4) nanoparticles and chitosan (CS) were mixed to form a matrix in which
      haemoglobin (Hb) can be immobilized for the fabrication of H(2)O(2) biosensor.
      The Fe(3)O(4)-CS-Hb film exhibited a pair of well-defined and quasi-reversible
      cyclic voltammetric peaks due to the redox of Hb-heme Fe (III)/Fe (II) in a pH
      7.0 phosphate buffer. The formal potential of Hb-heme Fe(III)/Fe(II) couple
      varied linearly with the increase of pH in the range of 4.0-10.0 with a slope of
      46.5 mV pH(-1), indicating that electron transfer was accompanied with single
      proton transportation in the electrochemical reaction. The surface coverage of Hb
      immobilized on Fe(3)O(4)-CS film glassy carbon electrode was about 1.13 x 10(
      10)mol cm(-2). The heterogeneous electron transfer rate constant (k(s)) was 1.04
      s(-1), indicating great facilitation of the electron transfer between Hb and
      magnetic nanoparticles-chitosan modified electrode. The modified electrode showed
      excellent electrocatalytic activity toward oxygen and hydrogen peroxide
      reduction. The apparent Michaelis-Menten constant K(M)(app) for H(2)O(2) was
      estimated to be 38.1 micromol L(-1).

PMID- 19576446
TI  - Immunomagnetic separation and rapid detection of bacteria using bioluminescence
      and microfluidics.
AB  - This paper describes an immunomagnetic separation of target bacterial cells from
      others by using magnetic bead. The surface of bead was coated with antibodies
      which can capture specific organism. The binding efficiency of immunomagnetic
      bead (IMB) capturing target bacterial cells was higher than 98% when the
      concentrations of target and interferent bacterial cells were at the same level.
      The concentration of bacteria was determined indirectly by detecting adenosine 5'
      triphosphate (ATP) employing bioluminescence (BL) reaction of firefly luciferin
      ATP. Benzalkonium chloride (BAC) was used as an ATP extractant from living
      bacterial cells. We found that BAC could enhance the light emission when the
      concentration of BAC was less than 5.3 x 10(-2)% (w/v) and the BL intensity
      reached its maximum at the concentration of BAC was 2.7 x 10(-2)%, which was 10
      fold stronger than that without BAC. Based on the principle of the IMB, a
      microfluidic chip combined with immunofluorescence assay for separating and
      detecting bacteria simultaneously was also developed. The IMBs were magnetically
      fixed in the bead-beds of chip channels with a 3-mm diameter of NdFeB permanent
      magnet. The target bacterial cells can be captured magnetically and observed by a
      fluorescent microscope.

PMID- 19576447
TI  - Validation of an environmental friendly segmented flow method for the
      determination of phenol index in waters as alternative to the conventional one.
AB  - Phenolic compounds are a sort of common pollutants in water. Phenol index becomes
      an expedite indicator for the evaluation of the contamination level of water
      samples, in spite of the knowledge of the individual phenol and its derivatives
      are also important. In this work, an environmental friendly method for the
      determination of phenols, using a segmented flow system based on the conventional
      method's reactions without the liquid-liquid extraction step, was validated.
      Three linear dynamic ranges using C(6)H(5)OH: 1-10 microg l(-1), 10-200 microg l(
      1) and 0.2-2.5 mg l(-1), with a coefficient of variation lower than 2%, were
      obtained. Several method's performance parameters were determined: limits of
      detection, limits of quantification, precision through duplicate analysis and
      trueness using the reference materials purchased from LGC Promochem, RTC no. QCI
      043-2 Lot:P1. Measurement uncertainty was evaluated using an interlaboratory
      approach based on proficiency testing data. Relative combined uncertainty for
      phenols in water samples, u(c)(rel)(gamma(sample)), of 0.054 were obtained, in
      according to those imposed by the Portuguese Legislation: target
      u(c)(rel)(gamma(sample))=0.58 for 1 microg l(-1) of phenol (surface waters) and
      target u(c)(rel)(gamma(sample))=0.06 for 500 microg l(-1) of phenol
      (wastewaters). A high efficiency reduction and elimination of reagents and
      wastes, reduction of analysis time and exposition of the analyst were also
      obtained.

PMID- 19576448
TI  - Magnesium effect on the acetylcholinesterase inhibition mechanism: a molecular
      chromatographic approach.
AB  - The acetylcholinesterase enzyme (AChE) was immobilized on a chromatographic
      support to study the effect of magnesium on the binding mechanism of five AChE
      inhibitors (donepezil, tacrine, galanthamine, physostigmine and huperzine). The
      determination of the enthalpy and entropy changes of this binding at different
      magnesium concentration values suggested that van der Waals interactions and
      hydrogen bonds predominated the donepezil and tacrine association to AChE. As
      well, hydrophobic and electrostatic forces seemed to be the major interactions
      controlling the huperzine, galanthamine and physostigmine association with AChE.
      In addition, it appeared that magnesium cation increased the binding affinity of
      galanthamine and physostigmine to the active site gorge of AChE. A comparison of
      the inhibitors hydrophobicity to their relative bound percentage with AChE showed
      an affinity enhanced with the increase in the molecule hydrophobicity and
      confirmed that the hydrophobic forces played an important role in the AChEI-AChE
      binding process. This novel biochromatographic column could be useful to find a
      specific inhibitor for this enzyme and so open new perspectives to be
      investigated.

PMID- 19576449
TI  - The development and inter-laboratory verification of LC-MS libraries for organic
      chemicals of environmental concern.
AB  - The development, verification, and comparison study between LC-MS libraries for
      two manufacturers' instruments and a verified protocol are discussed. Compounds
      in the libraries are among those considered by the U.S. EPA Office of Water as
      threats to drinking water including pesticides, drugs of abuse, and
      pharmaceuticals. The LC-MS library protocol was verified through an inter
      laboratory study that involved Federal, State, and private laboratories. The
      results demonstrated that the libraries are transferable between the same
      manufacturer's product line, and have applicability between manufacturers.
      Although ion abundance ratios within mass spectra were shown to be different
      between the manufacturers' instruments, the NIST search engine match probability
      was at 96% or greater for 64 out of 67 compounds evaluated.

PMID- 19576450
TI  - A practical method for sensitive determination of the fluorescent water-tracer
      uranine by reversed phase HPLC under alkaline conditions.
AB  - A stable and highly sensitive HPLC method for uranine has been developed. Because
      of unstableness of silica-based octadecyl-C18 columns at high pH condition, a
      reversed phase HPLC analysis under alkaline conditions has not necessarily taken
      as a usual method. However, the application for uranine seems to be advantageous,
      since the fluorescence yield of uranine is markedly enhanced at high pH
      condition. The detection limit of the HPLC system was 0.9 pg. The analytical
      consideration was also paid for the solid phase extraction (SPE) prior to the
      HPLC analysis with careful consideration of the recently revised pK(a) values of
      uranine. The recovery rate of uranine by SPE was found to depend on the sample
      volume and a few ml of seawater was applied to SPE in order to maintain the
      recovery rate during SPE. A combination of HPLC and SPE methods achieved
      detection of uranine at concentrations as low as 0.2 ng l(-1) (0.5 pM), which was
      comparable to the background concentration of uranine in coastal water off Japan.
      For the practical use of the detected tracer-uranine concentration values after
      substantial duration after release, the photodegradation of uranine in surface
      water was also evaluated in terms of incident solar radiation dose as an
      exponential rate constant of -0.135 mol photon(-1)m(2).

PMID- 19576451
TI  - Determination of organophosphate flame retardants and plasticizers in sediment
      samples using microwave-assisted extraction and gas chromatography with
      inductively coupled plasma mass spectrometry.
AB  - A procedure for the determination of 10 organophosphates, used as flame
      retardants and plasticizers, in sediment samples is presented. Microwave-assisted
      extraction (MAE) and gas chromatography with inductively coupled plasma mass
      spectrometry (GC-ICP-MS) were used for sample preparation and analytes
      determination, respectively. Influence of different variables on the performance
      of extraction and determination processes is thoroughly discussed. Temperature,
      type and amount of organic solvent showed a major effect on the yield of MAE.
      Regarding GC-ICP-MS detection, the combination of pulsed splitless injection with
      low radio frequency (rf) power, hard extraction conditions (referred to lens
      voltage) and addition of nitrogen (0.03 L min(-1)) to the argon plasma provided
      the best sensitivity. Under final working conditions, recoveries between 78% and
      105%, for samples spiked at different concentration levels, and limits of
      quantification from 2 to 4 ng g(-1) were achieved. Analysis of unspiked sediments
      confirmed the excellent selectivity of the proposed method for real-life polluted
      sample analysis.

PMID- 19576452
TI  - A versatile total internal reflection photometric detection cell for flow
      analysis.
AB  - A total internal reflection (TIR) flow-through cell that is highly tolerant of
      schlieren effects, has limited hydrodynamic dispersion and does not trap gas
      bubbles, and which is suitable for sensitive photometric measurements in flow
      analysis, is described. Light from an optical fibre is introduced into a short
      length of quartz capillary through the sidewall at an incident angle of ca. 53
      degrees. Under this condition, incident light undergoes total internal reflection
      from the external air-quartz interface and is propagated by successive
      reflections from the external walls through the aqueous liquid core of the cell.
      Detection of the transmitted beam is enabled by intentionally introducing an
      optical coupling medium at a predetermined distance along the capillary wall,
      which allows the internally reflected light to be captured by a second optical
      fibre connected to a charge-couple device detector. This configuration embodies a
      number of the desirable features of a liquid core waveguide cell (i.e. total
      internal reflection), a multi-reflection (MR) flow cell (i.e. minimum
      susceptibility to schlieren effects, low hydrodynamic dispersion and little
      tendency to trap bubbles), and a conventional Z-cell (wide dynamic range). When
      employed with a flow injection system, a limit of detection of 2.0 microg PL(-1)
      was achieved for the determination of reactive phosphate using the TIR cell,
      compared with LOD values of 3.8 microg PL(-1) and 4.9 microg PL(-1) obtained
      using the MR and Z-cells with same manifold. The combined advantages of schlieren
      tolerance and lack of bubble entrapment of the MR cell with the higher S/N ratio
      and wider dynamic range of a conventional Z-cell, make the TIR cell eminently
      useful for photometric measurements of samples with widely differing refractive
      indices.

PMID- 19576453
TI  - Metabonomics study of atherosclerosis rats by ultra fast liquid chromatography
      coupled with ion trap-time of flight mass spectrometry.
AB  - An ultra fast liquid chromatography coupled with IT-TOF mass spectrometry
      (UFLC/MS-IT-TOF) metabonomic approach was employed to study the plasma and urine
      metabolic profiling of atherosclerosis rats. Acquired data were subjected to
      principal component analysis (PCA) for differentiating the atherosclerosis and
      the control groups. Potential biomarkers were screened by using S-plot and were
      identified by the accurate mass and MS(n) fragments information obtained from
      UFLC/MS-IT-TOF analysis. 12 metabolites in rat plasma and 8 metabolites in urine
      were identified as potential biomarkers. Concentrations of leucine,
      phenylalanine, tryptophan, acetylcarnitine, butyrylcarnitine, propionylcarnitine
      and spermine in plasma and 3-O-methyl-dopa, ethyl N2-acetyl-L-argininate,
      leucylproline, glucuronate, t6A N(6)-(N-threonylcarbonyl)-adenosine and methyl
      hippuric acid in urine decreased in atherosclerosis rats. Ursodeoxycholic acid,
      chenodeoxycholic acid, LPC (C16:0), LPC (C18:0) and LPC (C18:1) in plasma and
      hippuric acid in urine were in higher levels in atherosclerosis rats. The
      alterated metabolites demonstrated abnormal metabolism of phenylalanine,
      tryptophan, bile acids and amino acids. This research proved that metabonomics is
      a promising tool for disease research.

PMID- 19576454
TI  - Simple and rapid voltammetric determination of morphine at electrochemically
      pretreated glassy carbon electrodes.
AB  - A simple and rapid method for morphine detection has been described based on
      electrochemical pretreatment of glassy carbon electrode (GCE) which was treated
      by anodic oxidation at 1.75 V, following potential cycling in the potential range
      from 0 V to 1.0 V vs. Ag|AgCl reference electrode. The sensitivity for morphine
      detection was improved greatly and the detection limit was 0.2 microM. The
      reproducibility of the voltammetric measurements was usually less than 3% RSD for
      six replicate measurements. Moreover, this method could readily discriminate
      morphine from codeine. And an electrochemical detection of morphine in spiked
      urine sample was succeeded with satisfactory results.

PMID- 19576455
TI  - Establishing linear solvation energy relationships between VOCs and monolayer
      protected gold nanoclusters using quartz crystal microbalance.
AB  - Linear solvation energy relationships (LSERs) have been recognized as a useful
      model for investigating the chemical forces behind the partition coefficients
      between vapor molecules and absorbents. This study is the first to determine the
      solvation properties of monolayer-protected gold nanoclusters (MPCs) with
      different surface ligands. The ratio of partition coefficients/MPC density
      (K/rho) of 18 volatile organic compounds (VOCs) for four different MPCs obtained
      through quartz crystal microbalance (QCM) experiments were used for the LSER
      model calculations. LSER modeling results indicate that all MPC surfaces showed a
      statistically significant (p<0.05) preference to hydrogen-bond acidic molecules.
      Through dipole-dipole attraction, 4-methoxythiophenol-capped MPCs can also
      interact with polar organics (s=1.04). Showing a unique preference for the
      hydrogen bond basicity of vapors (b=1.11), 2-benzothiazolethiol-capped MPCs
      provide evidence of an intra-molecular, proton-shift mechanism on surface of nano
      gold.

PMID- 19576456
TI  - Combined on-line transmission FTIR measurements and BTEM analysis for the kinetic
      study of a consecutive reaction in aqueous-organic phase medium.
AB  - Combined on-line transmission FTIR spectroscopy and band-target entropy
      minimization (BTEM) analysis were employed in order to monitor and analyze the
      kinetics of the alkaline hydrolysis reaction of diethyl phthalate (DEP) in
      aqueous-ethanol solvent mixture. This reaction is irreversible and involves two
      consecutive steps with the formation of the observable mono-ion intermediate
      species. The pure component mid-FTIR spectra of the reactive species involved in
      this reaction, namely DEP, mono-ion intermediate and di-ion product were
      successfully reconstructed using BTEM. Their corresponding concentrations were
      also calculated and subsequently employed to derive the kinetic rate parameters.
      The effect of temperature and the solvent mixture compositions on these two
      consecutive reaction steps were also discussed. The temperature variation study
      showed that both reaction rate coefficients increased with temperature. Both rate
      coefficients were also affected by the solvent mixture compositions and reached
      minimum values at certain water-ethanol solvent composition (circa 60% (v/v)).
      This study shows the utility of combined on-line transmission FTIR spectroscopy
      and chemometric techniques for the present, rather complex, consecutive organic
      reaction. Moreover, the present type of approach could facilitate better
      understanding of a wide variety of organic reactions that are performed in
      aqueous and mixed aqueous-organic solvents.

PMID- 19576457
TI  - Batch and flow measurement of hydrogen ions in highly acidic media using 2-(4
      methoxy phenyl) 6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo [3.1.0] hex-3-ene as
      an H+-selective ionophore.
AB  - A hydrogen ion-selective poly(vinyl chloride) (PVC) membrane electrode was
      developed using 2-(4-methoxy phenyl) 6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo
      [3.1.0] hex-3-ene as ionophore. Effects of experimental parameters such as
      membrane composition, nature and amount of plasticizer, and the amount of
      additive on the potential response of pH sensor were investigated. This H(+)
      selective membrane electrode gave a linear response over the pH range 0-4 (10(-4)
      to 1 mol L(-1) HCl) with slope of 57.4+/-0.3 mV pH(-1) and limit of detection 6.3
      x 10(-5)mol L(-1) at 20 degrees C. Also, hydrofluoric acid did not influence the
      surface of this electrode and thus it was maintained without showing any changes
      in potentials after being used in a hydrofluoric acid solution. The equilibrium
      water content of the electrode was determined in the presence of two different
      plasticizers as membrane solvent. The alkaline cation binding affinity of
      ionophore was very low that prove these cations do not have specific interaction
      with this ionophore. The electrode had fairly low electrical resistance, good
      potential stability and reproducibility. It has a rapid potential response to
      changes of pH (10s), easily used in a single channel wall-jet flow injection
      system with good reproducibility (RSD%=1.67%) and high reversibility. It was used
      as indicator electrode in potentiometric determination of pH in real samples.

PMID- 19576459
TI  - Factors affecting the reactivity of thiol-functionalized mesoporous silica
      adsorbents toward mercury(II).
AB  - Numerous mercaptopropyl-functionalized silica spheres have been prepared by
      either post-synthesis grafting of MCM-41 and MCM-48 or self-assembly co
      condensation of mercaptopropyltrimethoxysilane (MPTMS) or
      mercaptopropyltriethoxysilane (MPTES) and tetraethoxysilane (TEOS) precursors in
      hydroalcoholic medium in the presence of a cationic surfactant as templating
      agent and ammonia as catalyst. These materials of approximately the same particle
      size and morphology featured different functionalization levels, various degrees
      of structural order, and variable distribution of thiol groups in the mesopores.
      Their reactivity in solution has been studied using Hg(II) as model analyte.
      Total accessibility (on a 1:1 S:Hg stoichiometry basis) was demonstrated and
      quantified for well-ordered materials whereas less open and less organized
      structures with high degrees of functionalization were subject to less-than
      complete loadings. Capacities measured at pH 2 were lower than at pH 4 because of
      distinct mercury-binding mechanisms. Kinetics associated to the uptake process
      were studied by in situ electrochemical monitoring of Hg(II) consumption from
      aqueous suspensions containing the various adsorbents. They indicate only little
      difference between materials of the MCM-41 and MCM-48 series at similar
      functionalization levels, fast mass transport in well-ordered mesostructures in
      comparison to the poorly or non-ordered ones (except at pH 2 where charge
      formation induced some restriction in materials characterized by long-range
      structural order), and even faster processes in the wormlike frameworks
      (characterized by shorter range structural order). Hg(II) binding to thiol
      functionalized materials obtained by post-synthesis grafting was found to occur
      more rapidly in the early beginning of the uptake process as a result of a higher
      concentration of binding sites at the pore entrance in comparison to the more
      homogeneous distribution of these groups in the mesochannels of materials
      obtained by co-condensation.

PMID- 19576458
TI  - Comparison of extraction methods for volatile compounds of Muscat grape juice.
AB  - Typical flavour of Muscat d'Alexandrie wines is mainly due to volatile compounds
      coming from grapes of this variety. Therefore, the choice of grapes is crucial to
      obtain musts with a great aromatic potential, which will contribute to the final
      aroma of wines derived from those musts. In this study, three sampling
      techniques, liquid-liquid extraction (LLE), solid phase extraction (SPE) and
      simultaneous distillation-extraction (SDE), were compared for the analysis of
      volatile compounds in Muscat grape juice. Results showed that although the three
      techniques can be recommended for the quantitative analysis of volatile compounds
      from musts, LLE and SPE are better sample preparation techniques than SDE, mainly
      for determination of polar compounds such as acids or alcohols.

PMID- 19576460
TI  - Determining the adulteration of spices with Sudan I-II-II-IV dyes by UV-visible
      spectroscopy and multivariate classification techniques.
AB  - We propose a very simple and fast method for detecting Sudan dyes (I, II, III and
      IV) in commercial spices, based on characterizing samples through their UV
      visible spectra and using multivariate classification techniques to establish
      classification rules. We applied three classification techniques: K-Nearest
      Neighbour (KNN), Soft Independent Modelling of Class Analogy (SIMCA) and Partial
      Least Squares Discriminant Analysis (PLS-DA). A total of 27 commercial spice
      samples (turmeric, curry, hot paprika and mild paprika) were analysed by
      chromatography (HPLC-DAD) to check that they were free of Sudan dyes. These
      samples were then spiked with Sudan dyes (I, II, III and IV) up to a
      concentration of 5 mg L(-1). Our final data set consisted of 135 samples
      distributed in five classes: samples without Sudan dyes, samples spiked with
      Sudan I, samples spiked with Sudan II, samples spiked with Sudan III and samples
      spiked with Sudan IV. Classification results were good and satisfactory using the
      classification techniques mentioned above: 99.3%, 96.3% and 90.4% of correct
      classification with PLS-DA, KNN and SIMCA, respectively. It should be pointed out
      that with SIMCA, there are no real classification errors as no samples were
      assigned to the wrong class: they were just not assigned to any of the pre
      defined classes.

PMID- 19576461
TI  - Indirect chemiluminescence-based detection of mefenamic acid in pharmaceutical
      formulations by flow injection analysis and effect of gold nanocatalysts.
AB  - A highly sensitive flow injection-chemiluminescence detection (FI-CL) method
      based on periodate oxidation of two popular luminescent compounds for the
      determination of mefenamic acid (MFA) is presented. The method is an indirect CL
      detection method based on the CL emission generated during the oxidation of
      Pyrogallol (Pg) or Luminol (Lu) with the excess of periodate that remains after
      oxidation of MFA within the time period of 15 min. The MFA calibration curves
      obtained with either luminescent compounds were linear over a wide concentration
      range, depending on the system employed, offering detection limits in the range
      of low to ultra-low microg L(-1) levels. Gold nanoparticles (Au-NPs) were also
      assessed as means for enhancing the CL signal. Pg-periodate was not affected by
      the presence of gold nanocatalysts as opposed to Lu-periodate CL signal which
      exhibited a significant increase in the presence of citrate synthesized Au-NPs.
      The reproducibility of the method, expressed by the relative standard deviation
      (R.S.D.), was very satisfactory and always below 5% as evidenced by repeated
      measurements (n>or=10) of standard solutions at two concentration levels (2 and
      20 microg L(-1)).

PMID- 19576462
TI  - Determination of low level nitrite and nitrate in biological, food and
      environmental samples by gas chromatography-mass spectrometry and liquid
      chromatography with fluorescence detection.
AB  - Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with
      fluorescence detection (LC-FL) methods have been proposed for the determination
      of low level nitrite and nitrate in biological, food and environmental samples.
      The methods include derivatization of aqueous nitrite with 2,3-diaminonaphthalene
      (DAN), enzymatic reduction of nitrate to nitrite, extraction with toluene and
      chromatographic analyses of highly fluorescent 2,3-naphthotriazole (NAT)
      derivative of nitrite by using GC-MS in selected-ion-monitoring (SIM) mode and LC
      FL. Nitrite and nitrate ions in solid samples were extracted with 0.5M aqueous
      NaOH by sonication. The recoveries of nitrite and nitrate ions based on GC-MS and
      LC-FL results were 98.40% and 98.10% and the precision of these methods, as
      indicated by the relative standard deviations (RSDs) were 1.00% for nitrite and
      1.20% for nitrate, respectively. The limits of detection of the GC-MS in SIM mode
      and LC-FL methods based on S/N=3 were 0.02 and 0.29 pg/ml for nitrite and 0.03
      and 0.30 pg/ml for nitrate, respectively.

PMID- 19576463
TI  - Use of QSAR methods for predicting the chemiluminescent behaviour of organic
      compounds upon reaction with potassium permanganate in an acid medium.
AB  - In previous work, molecular connectivity computations were successfully used to
      predict the chemiluminescent behaviour of organic compounds upon reaction with
      common strong oxidants and the native fluorescence too; both of them in a liquid
      phase. The obtained results were used to develop new analytical procedures to the
      given compounds. For the first time, connectivity methods were used for a purely
      analytical purpose. In this work, we went deeper into the knowledge of direct
      chemiluminescence processes by using molecular connectivity in the form of QSAR
      methods to predict the chemiluminescence intensity produced by reactions between
      organic compounds (pharmaceuticals mainly) and potassium permanganate in a liquid
      phase. The choice of this oxidant was dictated by its being the most active by
      far in producing chemiluminescence. We used discriminant analysis to examine the
      results for 63 substances the emission intensity of which upon reaction with acid
      potassium permanganate was experimentally measured in a continuous-flow manifold.
      Descriptors were chosen by applying stepwise linear dicriminant analysis (LDA) to
      Snedecor F-values, using the smallest Mahalanobis distance, the minimum error on
      the test set and the lowest value of the Wilks'lambda as sorting criterion. The
      theoretical predictions thus obtained were checked against the experimental
      results for a set of 16 compounds not used in the previous theoretical
      computations the chemiluminescent behaviour of which was also experimentally
      assessed. The result was a hit rate of 87.5% in the predictions.

PMID- 19576464
TI  - Hollow fiber-based liquid-phase microextraction (HF-LPME) of ibuprofen followed
      by FIA-chemiluminescence determination using the acidic permanganate-sulfite
      system.
AB  - Hollow fiber-based liquid-phase microextraction (HF-LPME) is a relatively new
      technique employed in analytical chemistry for sample pretreatment which offers
      more selectivity and sensitivity than any traditional extraction technique. This
      paper describes a three-phase HF-LPME method for ibuprofen using a polypropylene
      membrane supporting dihexyl ether followed by a chemiluminescence (CL)
      determination using the CL enhancement on the acidic permanganate-sulfite system
      in a FIA configuration which is the first time that both techniques have been
      combined for analytical purposes. The CL intensity (peak area) was proportional
      to the log of ibuprofen concentration in the donor phase over the range 0.1-20
      microg mL(-1). The detection limit was 0.03 microg mL(-1) of ibuprofen in the
      donor phase. The method was satisfactory reproducible and has been applied to the
      ibuprofen determination in pharmaceuticals and in real human urine samples.

PMID- 19576465
TI  - Extending the working calibration ranges of four hexachlorocyclohexane isomers in
      gas chromatography-electron capture detector by radial basis function neural
      network.
AB  - A radial basis function neural network (RBFNN) method was developed for the first
      time to model the nonlinear calibration curves of four hexachlorocyclohexane
      (HCH) isomers, aiming to extend their working calibration ranges in gas
      chromatography-electron capture detector (GC-ECD). Other 14 methods, including
      seven parametric curve fitting methods, two nonparametric curve fitting methods,
      and five other artificial neural network (ANN) methods, were also developed and
      compared. Only the RBFNN method, with logarithm-transform and normalization
      operation on the calibration data, was able to model the nonlinear calibration
      curves of the four HCH isomers adequately. The RBFNN method accurately predicted
      the concentrations of HCH isomers within and out of the linear ranges in
      certified test samples. Furthermore, no significant difference (p>0.05) was found
      between the results of HCH isomers concentrations in water samples calculated
      with RBFNN method and ordinary least squares (OLS) method (R(2)>0.9990).
      Conclusively, the working calibration ranges of the four HCH isomers were
      extended from 0.08-60 ng/ml to 0.08-1000 ng/ml without sacrificing accuracy and
      precision by means of RBFNN. The outstanding nonlinear modeling capability of
      RBFNN, along with its universal applicability to various problems as a "soft"
      modeling method, should make the method an appealing alternative to traditional
      modeling methods in the calibration analyses of various systems besides the GC
      ECD.

PMID- 19576466
TI  - Determination of tetracyclines in food samples by molecularly imprinted
      monolithic column coupling with high performance liquid chromatography.
AB  - A novel solid phase extraction (SPE) method for determination of tetracyclines
      (TCs) in milk and honey samples by molecularly imprinted monolithic column was
      developed. Using tetracycline (TC) as the template, methacrylic acid (MAA) as the
      functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker,
      methanol as the solvent, cyclohexanol and dodecanol as the mixed porogenic
      solvents, a TC imprinted monolithic column was prepared by in situ molecular
      imprinting technique for the first time, and the optimal synthesis conditions and
      the selectivity of TC imprinted monolithic column were investigated. The
      interfering substances in food samples and TCs can be separated successfully on
      imprinted column. Molecularly imprinted solid phase extraction (MISPE) coupling
      with C18 column was used to determinate the TCs in milk and honey. The recoveries
      of this method for six tetracyclines antibiotics such as tetracycline (TC),
      oxytetracycline (OTC), minocycline (MINO), chlortetracycline (CTC), metacycline
      (MTC) and doxycycline (DTC) were investigated, and high recoveries of 73.3-90.6%
      from milk samples and 62.6-82.3% from honey samples were obtained. A method for
      determination of TCs at low concentration level in milk and honey samples was
      successfully developed by using the monolithic column as the precolumn for solid
      phase extraction of six TCs compounds.

PMID- 19576467
TI  - In situ PEI and formic acid directed formation of Pt NPs/MWNTs hybrid material
      with excellent electrocatalytic activity.
AB  - A hybrid material based on Pt nanoparticles (Pt NPs) and multi-walled carbon
      nanotubes (MWNTs) was fabricated with the assistance of PEI and formic acid. The
      cationic polyelectrolyte PEI not only favored the homogenous dispersion of carbon
      nanotubes (CNTs) in water, but also provided sites for the adsorption of anionic
      ions PtCl(4)(2-) on the MWNTs' sidewalls. Deposition of Pt NPs on the MWNTs'
      sidewalls was realized by in situ chemical reduction of anionic ions PtCl(4)(2-)
      with formic acid. The hybrid material was characterized with TEM, XRD and XPS.
      Its excellent electrocatalytic activity towards both oxygen reduction in acid
      media and dopamine redox was also discussed.

PMID- 19576468
TI  - Non-chromatographic determination of ultratraces of V(V) and V(IV) based on a
      double column solid phase extraction flow injection system coupled to
      electrothermal atomic absorption spectrometry.
AB  - In this work, a non-chromatographic procedure for the on-line determination of
      ultratraces of V(V) and V(IV) is presented. The method involves a solid phase
      extraction-flow injection system coupled to electrothermal atomic absorption
      spectrometry (SPE-FI-ETAAS). The system holds two microcolumns (MC) set in
      parallel and filled with lab-made mesoporous silica functionalized with 3
      aminopropyltriethoxy silane (APS) and mesoporous silica MCM-41, respectively. The
      pre-concentration of V(V) is performed by sorption onto the first MC (C1) filled
      with APS at pH 3, whilst that of V(IV) is performed by sorption onto the second
      column (C2) filled with mesoporous silica MCM-41 at pH 5. Aqueous samples
      containing both analytes are loaded and, after pre-concentration (pre
      concentration factor PCF=10, sorption flow rate=1 mL min(-1), sorption time=10
      min), they are eluted in separate vessels with hydroxylammonium chloride (HC) 0.1
      mol L(-1) in HCl 0.5 mol L(-1) (elution volume=1 mL, elution flow rate=0.5 mL
      min(-1)). Afterwards, both analytes are determined through ETAAS with graphite
      furnace. Under optimized conditions, the main analytical figures of merit for
      V(V) and V(IV) are, respectively: detection limits (3s): 0.5 and 0.6 microg L(
      1), linear range: 2-100 microg L(-1) (both analytes), sensitivity: 0.015 and
      0.013 microg(-1)L and sample throughput: 6h(-1) (both analytes). Recoveries of
      both species were assayed in different water samples. Validation was performed
      through certified reference materials for ultratraces of total vanadium in river
      water.

PMID- 19576469
TI  - Microwave assisted extraction of iodine and bromine from edible seaweed for
      inductively coupled plasma-mass spectrometry determination.
AB  - The feasibility of microwave energy to assist the solubilisation of edible
      seaweed samples by tetramethylammonium hydroxide (TMAH) has been investigated to
      extract iodine and bromine. Inductively coupled plasma-mass spectrometry (ICP-MS)
      has been used as a multi-element detector. Variables affecting the microwave
      assisted extraction/solubilisation (temperature, TMAH volume, ramp time and hold
      time) were firstly screened by applying a fractional factorial design (2(5-1)+2),
      resolution V and 2 centre points. When extracting both halogens, results showed
      statistical significance (confidence interval of 95%) for TMAH volume and
      temperature, and also for the two order interaction between both variables.
      Therefore, these two variables were finally optimized by a 2(2)+star orthogonal
      central composite design with 5 centre points and 2 replicates, and optimum
      values of 200 degrees C and 10 mL for temperature and TMAH volume, respectively,
      were found. The extraction time (ramp and hold times) was found statistically non
      significant, and values of 10 and 5 min were chosen for the ramp time and the
      hold time, respectively. This means a fast microwave heating cycle. Repeatability
      of the over-all procedure has been found to be 6% for both elements, while iodine
      and bromine concentrations of 24.6 and 19.9 ng g(-1), respectively, were
      established for the limit of detection. Accuracy of the method was assessed by
      analyzing the NIES-09 (Sargasso, Sargassum fulvellum) certified reference
      material (CRM) and the iodine and bromine concentrations found have been in good
      agreement with the indicative values for this CRM. Finally, the method was
      applied to several edible dried and canned seaweed samples.

PMID- 19576470
TI  - Mg2+/Na+-doped rutile TiO2 nanofiber mats for high-speed and anti-fogged humidity
      sensors.
AB  - Mg(2+) and Na(+) doped rutile TiO2 nanofibers have been prepared through in situ
      electrospinning technique and calcination with poly(vinyl pyrrolidone) (PVP)
      nanofibers as sacrificed template. The as-prepared composite nanofibers are spin
      coated onto a ceramic substrate with three pairs of carbon interdigital
      electrodes to measure its humidity sensing behaviors. The product exhibits high
      speed response (2s) and recovery (1s) for detecting moisture. Additionally, under
      UV irradiation, a water contact angle (theta) of nearly 0 degrees has been
      observed based on the product, providing our humidity sensor with the anti-fogged
      properties.

PMID- 19576471
TI  - Surface modification of poly(dimethylsiloxane) microchips using a double-chained
      cationic surfactant for efficiently resolving fluorescent dye adsorption.
AB  - This paper described a double-chained cationic surfactant,
      didodecyldimethylammonium bromide (DDAB), for dynamic surface modification of
      poly(dimethylsiloxane) (PDMS) microchips to reduce the fluorescent dyes
      adsorption onto the microchannel. When DDAB with a high concentration was present
      as the dynamic modification reagent in the running and sample buffer, it not only
      reversed the direction of electroosmotic flow, but also efficiently suppressed
      fluorescent dyes pyronine Y (PY) or rhodamine B (RB) adsorption onto the chip
      surface. In addition, vesicles formed by DDAB in the buffer with higher surface
      charge density and electrophoretic mobility could provide wider migration window
      and potential for the separation of compounds with similar hydrophobicity.
      Factors affecting modification, such as pH and concentrations of the buffer, DDAB
      concentration in the buffer were investigated. Compared with commonly used single
      chained cetyltrimethylammonium bromide, DDAB provided a better modification
      performance. Furthermore, PY and RB were separated successfully on a PDMS
      microchip at the appropriate conditions with DDAB.

PMID- 19576472
TI  - Millisecond analysis of double stranded DNA with fluorescent intercalator by
      micro-thermocontrol-device.
AB  - Study of interaction between DNA and intercalator at molecular level is important
      to understand the mechanisms of DNA replication and repair. A micro-fabricated
      local heating thermodevice was adapted to perform denaturation experiments of DNA
      with fluorescent intercalator on millisecond time scale. Response time of
      complete unzipping of double stranded DNA, 16 microm in length, was measured to
      be around 5 min by commercial thermocycler. Response time of quenching of double
      stranded DNA with fluorescent intercalator SYBR Green was measured to be 10 ms.
      Thus, quenching properties owing to strand unzipping and denaturation at base
      pair level were distinguished. This method has provided easy access to measure
      this parameter and may be a powerful methodology in analyzing biomolecules on
      millisecond time scale.

PMID- 19576473
TI  - Evaluation of the suitability of sampling on Tenax TA and polydimethylsiloxane
      for the analysis of combustion gases.
AB  - Two sorbents commonly employed for air sampling were selected for the evaluation
      of their suitability for the analysis of combustion gases namely Tenax TA as
      adsorbent and polydimethylsiloxane (PDMS) as absorbent. Target compounds were
      selected among the gaseous combustion products of polyurethane foam and fire
      retarded polystyrene. The combustion gases were generated by burning test
      materials in the flame of a Bunsen burner. Gaseous combustion products were
      sampled simultaneously with the two sorbents using a two-way adapter, thereby
      exposing each sorbent to the same combustion gas atmosphere. Special attention
      was given to the deterioration encountered in the Tenax TA performance upon
      repeated combustion gas exposure, limiting its use for sampling reactive
      atmospheres.

PMID- 19576474
TI  - Study on homogeneous competitive immune reaction by fluorescence correlation
      spectroscopy: using synthetic peptide as antigen.
AB  - In this paper, fluorescence correlation spectroscopy (FCS) is used for
      investigation of homogeneous immune reaction using synthetic peptide as antigen.
      The binding process of CA125 peptide antigen and its antibody was systematically
      investigated. The dissociation constant and dissociation rate for antigen
      antibody complex were determined, which were k(diss)=0.94+/-0.05 nM and
      k(off)=0.00215+/-0.0001 s(-1), respectively. Under optimal conditions, the
      detection limit of the competitive immunoassay was 4 x 10(-10)M (S/N=3). The good
      recoveries were obtained with human serum samples. Our preliminary results
      demonstrated that the homogeneous competitive immunoassay based on FCS is simple,
      rapid, sensitive and small sample and reagent requirement, and this method maybe
      possess great potential applications in clinical diagnosis, food and
      environmental analyses and biological and biomedical studies.

PMID- 19576475
TI  - [Injection techniques for the upper part of the face: forehead and periocular
      region].
AB  - Botulinum toxin injections are first-line treatment for facial lines in the upper
      part of the face. The relatively easy injection techniques at the forehead, the
      glabellar region, and the periocular region make this treatment advantageous.
      This treatment requires good knowledge of the functional anatomy of the face and
      of the product used. After semeiologic analysis of facial aging, it provides
      results that respect the natural contours of the face, allowing one to adapt the
      treatment to each patient's wishes.

PMID- 19576476
TI  - [Botulinum toxin injection techniques in the lower third and middle of the face,
      the neck and the decollete: the "Nefertiti lift"].
AB  - Although correction of the dynamic wrinkles of the upper part of the face is the
      major indication for botulinum toxin, there are also many possibilities for the
      middle and lower thirds of the face and neck. However, these injections are more
      delicate and require an experienced operator who has excellent knowledge of the
      muscles of these regions, their functions, the antagonist actions exercised on
      other muscles, particularly in terms of the complex equilibrium of the mouth. An
      excessive dose, an inappropriate injection point, or a centering mistake can all
      easily be responsible for undesirable side effects. However, the results
      obtained, often with lower doses than in the superior part of the face, can be
      highly satisfactory, notably in erasing bunny lines, improvement of marionette
      lines, peau d'orange chin, attenuation of peribuccal lines, melomental folds,
      correction of a gummy smile, and facial asymmetries. In the neck it is possible
      to reduce platysmal bands, horizontal lines, and diagonal lines of the neck and
      decollete. The face contours can also be improved by the Nefertiti lift. In the
      mid and lower regions of the face, botulinum toxin is often a complement to other
      esthetic techniques, particularly filling procedures.

PMID- 19576477
TI  - [Botulin toxin injections in cosmetic treatment of men].
AB  - Men are showing increasing interest in nonsurgical esthetic procedures even if
      women account for the vast majority of patients. Botulinum toxin A injections are
      particularly sought by men: this is the most frequently performed nonsurgical
      procedure, with 296,000 injections in the US in 2007 (Fig. 1). Men seek to remain
      natural while retaining their maturity and improving their appearance. The
      classical injection technique does not differ in men and the basics are similar
      to procedures performed in women. However, they often require larger doses. In
      addition, men's facial morphology presents certain specificities that must be
      respected when choosing the injection points.

PMID- 19576478
TI  - [Management of axillary hyperhidrosis].
AB  - Hyperhidrosis is considered as an handicap which affects around of 2.8% of the
      population. It is linked to an extreme, permanent and symetric production of
      sweating because of an hyperactivity of sweat glands independant of thermo
      regulation process. The treatment by botulinum toxin has completely changed the
      treatment of axillary hyperhidrosis. It is an easy, quick, efficient treatment
      which improved quality of life of these patients. This treatment can also be used
      for palmar and plantar hyperhidrosis but it requires regional anesthetic
      technics, so it is done to the hospital.

PMID- 19576479
TI  - [Botulinum toxin in disabling dermatological diseases].
AB  - Botulinum toxin could represent nowadays a new treatment modality especially for
      cutaneous conditions in course of which conventional treatments remain
      unsuccessful. Besides palmar and plantar hyperhidrosis, botulinum toxin has
      demonstrated efficacy in different conditions associated with hyperhidrosis, such
      as dyshidrosis, multiple eccrine hidrocystomas, hidradenitis suppurativa, Frey
      syndrome, but also in different conditions worsened by hyperhidrosis such as
      Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar
      keratoderma, pachyonychia congenital. Moreover, different cutaneous conditions
      associated with sensitive disorders and/or neurological involvements could
      benefit from botulinum toxin, for example anal fissures, leg ulcers, lichen
      simplex, notalgia paresthetica, vestibulitis. Endly, a case of cutis laxa was
      described where the patient was improved by cutaneous injections of botulinum
      toxin.

PMID- 19576480
TI  - [Periocular aging: physiopathogenesis, clinical aspect, and treatment].
AB  - Aging around the eyes plays a considerable role in facial aging. The demand for
      periocular rejuvenation is increasingly frequent. Until the past few years,
      eyelid esthetics was synonymous with blepharoplasty: surgery that consisted in
      resecting the myocutaneous excesses and reducing fatty deposits. The contribution
      of new medical and surgical treatments combined with new and more rigorous
      analysis of the esthetic disorders makes it possible to respond more precisely to
      patient demand and individualize surgical and/or medical treatment that is not
      highly aggressive and only uses products that are well tolerated, biocompatible,
      or resorbable.

PMID- 19576481
TI  - [Hemifacial spasm].
AB  - Hemifacial spasm is one of the two most common craniofacial movement disorders
      (blepharospasm is the second one). It is characterised by unilateral involuntary
      contractions of muscles involved in facial expression that are innervated by the
      facial nerve. Most of the time, hemifacial spasm is a peripherally-induced
      movement disorder caused by vascular compression of the facial nerve near its
      origin from the brainstem. Although it is a benign condition, it can cause
      significant cosmetic and functional disability. It is a chronic disease and
      spontaneous recovery is very rare. The two treatments that are really efficient
      and routinely available are microvascular decompression and botulinum toxin
      muscular injections.

PMID- 19576482
TI  - [Prevention and management of locoregional complications of botulinum A toxin
      injections in cosmetic treatment].
AB  - Botulinum toxin serotype A injections used in treating dynamic wrinkles is one of
      the least invasive cosmetic procedures. High patient satisfaction and low onset
      of always moderate side effects contribute to the growing popularity of botulinum
      toxin injections in cosmetic treatment over the past few years. Years of
      experience and use, in therapeutics [1,2] and esthetics (20 years) have proven
      the efficacy and the safety of this wrinkle treatment. Today, no severe or long
      term side effects have been reported in esthetics. This article discusses only
      the most frequent locoregional effects. They are rare, moderate, transitory, and
      totally reversible. Properly informing and selecting patients will contribute to
      successfully preventing and managing these effects.

PMID- 19576483
TI  - [What's new in aesthetic dermatology: filler and laser treatments].
AB  - In esthetic dermatology, filling and laser treatments are two essential
      techniques. Several recent studies on calcium hydroxyapatite in filling
      treatments and facial volumetry, in esthetics, but also in HIV patients, have
      been published. It was also tested in accentuated melomental folds where it is
      superior to hyaluronic acid. In aging of the skin of the dorsal aspect of the
      hands, hyaluronic acid provides slightly better results than collagen. Filler
      rhinoplasty can correct minor deformations of the nose. Lipofilling is
      advantageous for linear scleroderma of the face, at least in the forehead region,
      and adipocyte stem cells may be a future solution for facial aging or
      lipoatrophy. The risk of local and/or general sarcoid reactions related to
      interferon in patients having undergone filling injections has been reported. In
      the field of laser treatment, fractionated photothermolysis has motivated much
      more research and seem particularly valuable in treating acne scars, aging of the
      dorsal aspect of the hands, and, more anecdotally, in colloid milium and pearly
      penile papules. Laser is also useful in preventing surgical scars where a mini
      diode can also be used. For axillary hyperhidrosis, subdermic Nd-YAG laser
      competes with botulinum toxin, with longer-lasting results. Solutions are
      appearing for treatment of red or white striae cutis distensae. Intense pulsed
      light is the reference technique for poikiloderma of Civatte, and seems
      effective, with new devices, for melasma. However, inappropriately used by
      nonphysicians, IPL can cause serious ocular accidents; one case of uveitis has
      been reported.

PMID- 19576484
TI  - [The Aesthetic and Corrective Dermatology Group of the French Society of
      Dermatology].

PMID- 19576485
TI  - [Introduction. Botulinum toxin].

PMID- 19576486
TI  - [A reminder of the structure and function of the skeletal neuromuscular
      junction].
AB  - The skeletal neuromuscular junction has been considered as a model of chemical
      synapses due to its relatively simple organization. It is made up of three
      cellular partners including the motoneuron nerve terminals, the peri-synaptic
      Schwann cells and a specialized region of skeletal muscle fibers. It has been
      extensively studied revealing its ultrastructural complexity involving many
      molecular actors. The neuromuscular junction is a highly specialized structure,
      optimized for the rapid transmission of information from the presynaptic nerve
      terminal to the post-synaptic muscle fiber. This rapid transmission requires a
      very close apposition of plasmic membranes of pre- and post-synaptic partners,
      and a strict structural and molecular arrangement on both sides of the narrow
      synaptic cleft separating nerve terminal and muscle membranes. In this short
      review, we summarize the knowledge regarding pre- and post-synaptic
      ultrastructural specializations and give an overview of some functional aspects
      of neuromuscular transmission, including the quantal acetylcholine release
      process, which will help to better understand the pharmacological actions of
      botulinum toxins in esthetic and corrective dermatology.

PMID- 19576487
TI  - [Facial anatomy and botulinum toxin: the muscular balances].
AB  - The muscular topographic anatomy of the face has long been known. The functional
      anatomy of the face has been studied by many neurologists, with Duchenne of
      Boulogne one of the first. The possibility of correcting not only wrinkles, but
      also certain regional balances gives botulinum toxin a certain number of
      advantages as well as limitations that should be well known by future injectors
      as well as the more experienced of practitioners who seek to treat the most
      difficult zones.

PMID- 19576488
TI  - [Muscular aging and its involvement in facial aging: the Face Recurve concept].
AB  - Cutaneous ageing is responsible for the increasingly creased appearance of the
      skin, pores opening, skin dyschromia, while the ageing of the structures of the
      face is attributed primarily to the effect of gravity on the tissues. The theory
      expounded below sets out to prove that the main and initial cause of this ageing
      is the repeated contractions of the mimic muscles. This concept attributes only a
      secondary role to gravity in the ageing process, which is initially brought about
      by muscular contractions. An MRI study recently made it possible to demonstrate
      the anterior convexity curve of the mimic muscles in the young subject. This
      curve is due to the existence of a deep fat pad at the back of these muscles.
      While this mass of fat is effectively a mechanical sliding plane, its convexity
      constitutes the founding principle behind this new ageing theory. In the young
      subject, the extent of its convexity and its location give a specific, youthful
      character to the movements, in terms of direction and amplitude, of the facial
      muscles. With age, the muscle gradually straightens and shortens, due to the
      repeated contractions that expel the underlying fat and increase the tonus at
      rest. The structural ageing becomes visible and with time, the expression of the
      subject is consequently more rigid.

PMID- 19576489
TI  - [Mechanisms of action of botulinum toxins and neurotoxins].
AB  - Several bacteria of the Clostridium genus (C. botulinum) produce 150 kDa di
      chainal protein toxins referred as botulinum neurotoxins or BoNTs. They associate
      with non-toxic companion proteins and form a complex termed botulinum toxin.
      BoNTs specifically inhibit vesicular neurotransmitter release. The cellular
      action of BoNTs can be depicted according to a multi-step model : The toxin's
      heavy chain mediates binding to specific receptors comprised of a ganglioside
      moiety and a vesicular protein (SV2 for BoNT type A, synaptotagmin for BoNT type
      B), followed by endocytotic internalisation of the BoNT/receptor complex. Vesicle
      recycling induces BoNT internalisation. Upon acidification of vesicles, the light
      chain of the neurotoxin is translocated into the cytosol. Here, this zinc
      endopeptidase cleaves one or two among three synaptic proteins (VAMP-synapto
      brevin, SNAP25, and syntaxin). As the three protein targets of BoNT play major
      role in fusion of synaptic vesicles at the release sites, their cleavage is
      followed by blockade of neurotransmitter exocytosis. Importantly, as the BoNT
      receptors and intracellular targets are present in all nerve terminals, the BoNTs
      are not specific for cholinergic transmission. Duration of their inhibitory
      action is mainly determined by the the life-time of the toxin's light chain in
      the cytosol. Sprouting of new nerve-endings, which are retracted when the
      poisoned nerve terminals have recovered full functionality, may lead to
      anticipated recovery of the poisoned nerve terminals.

PMID- 19576490
TI  - [Different botulinum toxins and their specifications].
AB  - Botulinum neurotoxin A was the first developed for therapeutic and then esthetic
      uses, Botox first and then Dysport. These two products differ on a few points,
      explaining their nonequivalence of units: American and British tests of the mouse
      LD50 units based on solutions that were not identical and 500microg vs 150microg
      serum albumin dose in the excipient. The neurotoxin- accessory protein complexes
      were also different: 900 kDa homogeneous for Botox, 500 kDa heterogeneous for
      Dysport, giving greater diffusion for Dysport, but this is under debate and could
      result from an excessive conversion ratio. Clinical comparative studies, often
      with weak methodology, have defined an ideal ratio between these two products,
      guaranteeing efficacy, but without an overly pronounced diffusion. In the first
      publications for neurological and ophthalmological indications, the conversion
      ratio between Dysport and Botox was high, 4:1, and sometimes higher. However,
      today, particularly for cosmetic indications, the trend is toward a much lower
      ratio, 2.5:1, or perhaps less for dyshidrosis. This lower ratio has an economic
      incidence: Dysport is less expensive and therefore more competitive. The price of
      Dysport's cosmetic product, Azzalure, compared to the price of Vistabel, which is
      Botox's cosmetic presentation, has not yet been defined in France. The other A
      toxins, Xeomin, and the Asian toxins, MyoBloc (botulinum toxin type B), tested
      compared to Botox, have a slightly lower efficacy.

PMID- 19576491
TI  - [Long-term effects of botulinum toxin treatment].
AB  - Long-term BoNT treatment administration has been assessed in various treatment
      settings (especially in neurology), with the level and duration of BoNT efficacy
      response being maintained with no major safety problems. Most side effects are
      local one and are transient. The incidence of antibody development is low and
      does not induce significant concerns in clinical practice.

PMID- 19576492
TI  - [Controversy: botulinum toxin, does it prevent cutaneous aging?].
AB  - By blocking muscular contraction, even if this effect is reversible, botulinum
      toxin injected early and regularly to prevent aging modifies the facial traits
      and can result in muscular and cutaneous atrophy. Mechanical information is
      indispensable to cell survival and conditions the function of fibroblastic
      synthesis. Aging cannot be reduced to the facial lines; botulinum toxin cannot
      prevent the other parameters of age such as drying, pigmentation problems,
      vascular problems, and loss of volume.

PMID- 19576493
TI  - [Can the botulinum toxin prevent aging?].
AB  - This study wants to prouve that the resting tone is increasing with age. On the
      behalf of the Face Recurve concept, the deep fat is expelled superficially
      because of mimic muscle shortening. Botulinum toxin is proposed for a new
      indication: resting tone decrease in order to slow down muscle shortening and
      consequently structural aging. Injections can be performed very early in the
      ageing process, before the appearance at rest of wrinkle, only when it becomes
      visible in contraction. Precision of the injection is related to the recent
      determination of motor end plate location in every mimic muscle. Two classical
      uses, the maximum strength of contraction and the dermal injection, are
      associated to the action on the resting tone for more evolved cases. Finally, a
      new possibility for botulinum toxin injection is the blockage of muscular
      regeneration to stabilize the section of the age marker fascicules performed in
      the Face Recurve concept. This new indication is also useful in reconstructive
      surgery for treatment of the marginal mandibular lip deformity in patients with
      chronic unilateral facial palsies.

PMID- 19576494
TI  - Ophthalmology in the medical school curriculum: reestablishing our value and
      effecting change.

PMID- 19576495
TI  - A Prospective, randomized, investigator-masked evaluation of the monocular trial
      in ocular hypertension or open-angle glaucoma.
AB  - PURPOSE: To evaluate the clinical value of the monocular therapeutic drug trial
      in predicting long-term intraocular pressure (IOP) reduction. DESIGN:
      Prospective, randomized, investigator-masked trial. PARTICIPANTS: Twenty-six
      subjects with ocular hypertension or open-angle glaucoma. METHODS: Subjects
      attended 5 study visits: 2 on no IOP-lowering therapy, 1 on monocular therapy
      with latanoprost, and 2 on bilateral therapy. The monocular trial eye was
      randomly selected, and study personnel making IOP measurements were masked to
      randomization. The following parameters were calculated: the unadjusted IOP
      change (IOP in the randomized eye at the first on-treatment visit minus IOP in
      the same eye at the initiation of the monocular trial); the adjusted IOP change
      (the unadjusted IOP change minus the comparable IOP change in the untreated
      fellow eye between the same 2 visits); and the long-term IOP change (the
      difference of the mean of the 2 on-treatment IOP values during bilateral use and
      the mean of the 2 pretreatment IOP values). MAIN OUTCOME MEASURE: The
      relationship between short- and long-term IOP reduction, with the coefficient of
      determination (the square of the Pearson correlation coefficient, r) as the
      measure of association. RESULTS: The mean long-term IOP reduction after
      latanoprost therapy was -3.4+/-2.4 mmHg in first-treated eyes (P<0.0001) and 
      3.4+/-2.4 mmHg in second-treated eyes (P<0.0001). The mean unadjusted IOP
      reduction in the monocular trial eye was -3.1+/-3.4 mmHg; the correlation between
      the unadjusted IOP change and the long-term IOP change was weak to moderate
      (coefficient of determination 0.325). The mean adjusted IOP reduction was -2.8+/
      4.3 mmHg; the correlation between the adjusted IOP change and the long-term IOP
      change was also weak to moderate (coefficient of determination 0.279).
      CONCLUSIONS: The practice of adjusting the IOP change in the treated eye by the
      IOP change in the untreated eye--the monocular drug trial--is no more informative
      than using the treated eye's unadjusted IOP change, and both of these methods are
      poor predictors of long-term IOP reduction with latanoprost.

PMID- 19576496
TI  - Recurrent pterygium surgery using pterygium extended removal followed by extended
      conjunctival transplant: recurrence rate and cosmesis.
AB  - OBJECTIVE: To assess the rate of recurrence, complications, and cosmesis after
      recurrent pterygium removal with P.E.R.F.E.C.T. for PTERYGIUM (Pterygium Extended
      Removal Followed by Extended Conjunctival Transplant). DESIGN: A case series
      study of P.E.R.F.E.C.T. for PTERYGIUM was conducted by 1 surgeon with a 1-year
      follow-up to assess the recurrence, complication rate, and cosmesis.
      PARTICIPANTS: A total of 111 consecutive patients with recurrent pterygium
      removals. INTERVENTION: A major modification of conjunctival autograft surgery
      was used to treat recurrent pterygia. MAIN OUTCOME MEASURES: The recurrence rate,
      complications, and cosmesis after excision of recurrent pterygia using
      P.E.R.F.E.C.T. for PTERYGIUM. RESULTS: There were no patients with recurrence in
      111 consecutive patients, and all but 2 patients were followed for at least 1
      year. One patient developed an exotropia that required no treatment, and 1
      patient lost 4 lines of vision as a result of a corneal ulcer. CONCLUSIONS: In
      this series, P.E.R.F.E.C.T. for PTERYGIUM resulted in a zero recurrence rate (2
      patients lost to follow-up) with few complications and a good cosmetic
      appearance.

PMID- 19576498
TI  - In vivo laser confocal microscopy after non-Descemet's stripping automated
      endothelial keratoplasty.
AB  - OBJECTIVE: To investigate in vivo corneal changes in patients with bullous
      keratopathy who underwent non-Descemet's stripping automated endothelial
      keratoplasty (nDSAEK) with the use of laser confocal microscopy. DESIGN: Single
      center, prospective clinical study. PARTICIPANTS: Ten eyes (10 patients; 3 men
      and 7 women; mean age, 73.5+/-6.6 years [mean+/-standard deviation]) with bullous
      keratopathy were evaluated in this study. TESTING: In vivo laser confocal
      microscopy was performed before and 1, 3, and 6 months after nDSAEK. MAIN OUTCOME
      MEASURES: Selected confocal images of corneal layers were evaluated qualitatively
      and quantitatively for degree of haze and density of deposits. RESULTS: Before
      surgery, the following were observed in all patients: corneal epithelial edema,
      subepithelial haze, keratocytes in a honeycomb pattern, and tiny needle-shaped
      materials in the stroma. After nDSAEK, subepithelial haze, donor-recipient
      interface haze, and interface particles were observed in all measurable cases;
      postoperative haze, interface particles, and needle-shaped materials decreased
      statistically significantly (P<0.05) over the course of follow-up. In addition,
      hyperreflective giant interface particles were observed after nDSAEK in all
      patients. CONCLUSIONS: In vivo laser confocal microscopy can identify subclinical
      corneal abnormalities after nDSAEK such as subepithelial haze, host-recipient
      interface haze, host stromal needle-shaped materials, and host-recipient
      interface particles with characteristic giant particles. Further studies with
      this technology in a large number of patients and long-term follow-up are needed
      to understand fully the long-term corneal stromal changes after nDSAEK.

PMID- 19576497
TI  - Herpes simplex virus keratitis: histopathologic inflammation and corneal
      allograft rejection.
AB  - OBJECTIVE: To identify whether histopathologic and immunoassay biomarkers of
      inflammation are predictive for allograft rejection after penetrating
      keratoplasty (PKP) for herpes simplex virus (HSV) keratitis. DESIGN:
      Retrospective, interventional case series with prospective component of
      pathologic evaluation of frozen tissue. PARTICIPANTS: Sixty-two consecutive
      patients with HSV keratitis who underwent PKP. METHODS: A chart review and
      histopathologic examination of the excised host corneal button was performed to
      identify associations between clinical data and histopathologic presence of
      inflammation. Enzyme-linked immunosorbent assay for interleukin (IL)-8 and
      monocyte chemotactic protein-1 (MCP-1) chemokines and immunohistochemical
      staining for human leukocyte antigen (HLA)-DR and intercellular adhesion molecule
      1 (ICAM-1) antigens was also performed in inflamed and noninflamed specimens.
      MAIN OUTCOME MEASURES: To determine whether the presence of subclinical
      inflammation at the time of PKP predicts allograft rejection. RESULTS: Although
      81% of patients had clinically quiescent disease, histopathology revealed that
      74% had active corneal inflammation, a finding that was associated with the
      presence of clinical neovascularization (P = 0.01). Allograft rejections were
      experienced by 34% of the patients in this cohort. The histopathologic presence
      of inflammation was a risk factor for allograft rejection (P = 0.02). Corneal
      specimens demonstrating inflammation had significantly increased IL-8 (P =
      0.0005) and MCP-1 (P = 0.003) levels, and greater immunoreactivity for HLA-DR and
      ICAM-1 when compared with specimens without inflammation. Treatment with IL-10 ex
      vivo significantly inhibited IL-8 (P = 0.006), and MCP-1 (P = 0.01) chemokines,
      and qualitatively substantially reduced HLA-DR, but not ICAM-1, expression.
      CONCLUSIONS: Histopathologic inflammation is a risk factor for corneal allograft
      rejection.

PMID- 19576499
TI  - Endophthalmitis after pars plana vitrectomy a 20- and 25-gauge comparison.
AB  - OBJECTIVE: Recent retrospective analyses have suggested that postoperative
      endophthalmitis may be more frequent with 25- than 20-gauge pars plana vitrectomy
      (PPV). Because the infection risk may depend on the suturing status of the
      sclerotomy, and the perioperative anti-infection protocol, we compared the
      incidence rate of endophthalmitis after sutureless 25-gauge versus sutured 20
      gauge PPV on a large cohort of patients operated with a standardized
      perioperative anti-infection protocol. DESIGN: Retrospective comparative case
      series. PARTICIPANTS: Consecutive patients who underwent 20- or 25-gauge PPVs at
      a single center over a multi-year period. METHODS: We analyzed 3597 consecutive
      PPVs. Patients with a pre-PPV diagnosis of endophthalmitis, PPVs performed for
      implantation of drug delivery devices, or 25-gauge PPVs with all sclerotomies
      sutured closed were excluded. Patients with > or =1 week of follow-up were
      divided into 2 study groups by sclerotomy status at the end of surgery: the 20
      gauge group had 3 sutured 20-gauge sclerotomies, and the 25-gauge group had > or
      =1 unsutured 25-gauge sclerotomy. Endophthalmitis was defined by clinical
      criteria independent of microbiological results. MAIN OUTCOME MEASURES: The
      incidence of endophthalmitis was compared between 25- versus 20-gauge groups.
      RESULTS: Of 3372 PPV surgeries meeting inclusion and exclusion criteria, 1948 and
      1424 surgeries were 20- and 25-gauge PPVs, respectively. Average age (+/-
      standard deviation) of patients was 54.6 (+/- 22.6) and 64.4 (+/- 16.5) years in
      the 20- and 25-gauge PPV groups, respectively (P<0.0001). Median post-PPV follow
      up time was not significantly different between the 2 groups (12.5 vs 13.0
      months; P = 0.69). Endophthalmitis was observed in 1 patient (0.07%; 95%
      confidence interval, 0%-0.21%) from the 25-gauge group and none in the 20-gauge
      group (P = 0.42; Fisher exact test, 2-tailed). The use of air/gas endotamponade
      (P<0.0001) and intravitreal triamcinolone (P<0.001) was more common in 25- versus
      20-gauge PPV. CONCLUSIONS: The incidence of endophthalmitis was low in both
      groups. We were unable to show a significant difference in the incidence of
      endophthalmitis between sutureless 25-gauge and sutured 20-gauge PPV, and
      conclude that a careful perioperative anti-infection protocol may reduce 25-gauge
      PPV endophthalmitis risk to that of 20-gauge PPV.

PMID- 19576500
TI  - Population-based incidence of macular holes.
AB  - PURPOSE: To determine the incidence of full-thickness macular holes in Olmsted
      County, Minnesota. DESIGN: Population-based retrospective chart review (cross
      sectional study). PARTICIPANTS: Ninety-four eyes of 85 patients who were
      residents of Olmsted County, Minnesota. METHODS: A population-based retrospective
      chart review was performed for all diagnoses of macular hole between 1992 and
      2002 among residents of Olmsted County, Minnesota. Yearly incidence rates for
      each given age and sex group were determined by dividing the number of cases
      within that group by the estimated total Olmsted County resident population of
      the group for that given year. MAIN OUTCOME MEASURES: Documented clinical
      diagnosis of a macular hole. RESULTS: Idiopathic macular holes occur at an age-
      and sex-adjusted incidence in 7.8 persons and 8.69 eyes per 100,000 population
      per year in Olmsted County, Minnesota. The female-to-male ratio was determined to
      be 3.3 to 1, and bilateral idiopathic macular holes occurred in 11.7% of patients
      and accounted for 20.9% of the affected eyes. CONCLUSIONS: This study uniquely
      determined the incidence of macular holes in a predominantly Caucasian
      population.

PMID- 19576501
TI  - Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma
      release assay.
AB  - PURPOSE: To determine the role of the QuantiFERON-TB Gold In-Tube (QFT)
      (Cellestis Inc., Carnegie, Australia) assay in the diagnosis of tuberculosis (TB)
      uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: The study included 157
      patients with suspected TB uveitis seen over an 18-month period (August 1, 2006,
      to February 31, 2007) at the Singapore National Eye Center (SNEC) uveitis clinic.
      METHODS: We identified all cases of suspected TB uveitis in the above-mentioned
      time period and reviewed all medical records of the cases. Clinical findings,
      type of treatment instituted, response to treatment, and results of
      investigations such as QFT, tuberculin skin test (TST), and chest x-rays were
      recorded. A novel method of using treatment response to determine the presumed
      diagnosis of TB was used to estimate the accuracy of QFT and TST. MAIN OUTCOME
      MEASURES: The positive likelihood ratio (LR+), negative likelihood ratio (LR-),
      and area under the receiver operator characteristic curve (ROC) of the
      investigations were estimated. RESULTS: QFT is not superior to the TST in
      sensitivity as a screening test or first-line study in TB-related uveitis;
      however, QFT is more specific than the TST in identifying infections by
      Mycobacterium tuberculosis. Negative QFT tests should be interpreted with
      caution, because they do not exclude the diagnosis. CONCLUSIONS: The new QFT is
      only slightly superior to the TST in the diagnosis of TB uveitis. Thus, there is
      an important role for interpreting the QFT together with the TST. This is the
      first and largest study of its kind to evaluate the use of QFT in the clinical
      diagnosis of TB uveitis.

PMID- 19576502
TI  - Degos' disease.

PMID- 19576503
TI  - Angle closure glaucoma.

PMID- 19576505
TI  - Corneal thickness and glaucoma medications.

PMID- 19576507
TI  - Relative efficacy of prostaglandins.

PMID- 19576510
TI  - OCT Interpretation.

PMID- 19576511
TI  - Bilateral endophthalmitis due to dog bite.

PMID- 19576512
TI  - Internet studies.

PMID- 19576513
TI  - Neuroprotection by co-treatment and post-treating with calcitriol following the
      ischemic and excitotoxic insult in vivo and in vitro.
AB  - Several in vivo and in vitro studies have demonstrated the neuroprotective
      potential of pretreatment with 1alpha,25-dihydroxyvitamin D3 (calcitriol). The
      aim of the present study was to determine the effectiveness of calcitriol
      administered in vivo after a brain ischemic episode in the rat model of perinatal
      asphyxia, or when co-applied with or without delay during 24-h exposure of mouse
      hippocampal, neocortical and cerebellar neuronal cultures to glutamate on their
      7th and 12th day in vitro (7 DIV and 12 DIV, respectively). Calcitriol was also
      administered after acute exposure of rat cerebellar neurons to glutamate. In 7
      day-old rat pups subjected to hypoxia-ischemia, acute application of calcitriol
      in a single dose of 2 microg/kg, 30 min after termination of the insult, or
      subchronic, 7-day post-treatment with calcitriol, effectively reduced brain
      damage. The level of neuroprotection exceeded that achieved by hypoxic
      preconditioning used as the reference neuroprotective method. The results of in
      vitro experiments revealed the ability of calcitriol to reduce excitotoxicity in
      a manner dependent on the origin of the neuronal cells, their stage of maturation
      in culture and the duration of exposure to the excitotoxic insult before
      calcitriol application. Calcitriol was neuroprotective when it was administered
      together with glutamate or even after a delay of up to 6h during 24-h excitotoxic
      challenge of hippocampal and neocortical, but not cerebellar neuronal cultures.
      Application of calcitriol to cultured cerebellar granule neurons after acute
      exposure to glutamate was ineffective. In 12 DIV hippocampal cell cultures, 50 nM
      calcitriol inhibited glutamate-induced caspase-3 activity, while only 100 nM
      concentrations were effective in 7 DIV cultures. We ascribe the protective
      effects of calcitriol to the rapid modulation of mechanisms that are instrumental
      in the direct anti-apoptotic, neuroprotective action of this compound.

PMID- 19576514
TI  - Altered expression of tight junction proteins and matrix metalloproteinases in
      thiamine-deficient mouse brain.
AB  - Wernicke's encephalopathy (WE) in humans is a metabolic disorder caused by
      thiamine deficiency (TD). In both humans and experimental animals, TD leads to
      selective neuronal cell death in diencephalic and brainstem structures.
      Neuropathologic features of WE include petechial hemorrhagic lesions, and blood
      brain barrier (BBB) breakdown has been suggested to play an important role in the
      pathogenesis of TD. The goal of the present study was to examine expression of
      the tight junction (TJ) protein occludin, its associated scaffolding proteins
      zona occludens (ZO-1 and ZO-2), and to measure matrix metalloproteinase (MMP)
      levels as a function of regional BBB permeability changes in thiamine-deficient
      mice. TD was induced in 12-week-old male C57Bl/6 mice by feeding a thiamine
      deficient diet and administration of the central thiamine antagonist
      pyrithiamine. BBB permeability was measured by IgG extravasation; expression of
      occludin, ZO-1 and ZO-2 was measured by Western blot analysis and RT-PCR,
      structural integrity of the BBB was assessed using occludin and ZO-1
      immunostaining, and MMPs levels were measured by gelatin zymography and
      immunohistochemistry. Studies were performed in vulnerable (medial thalamus)
      versus spared (frontal cortex) regions of the brain. Hemorrhagic lesions,
      selective increases in brain IgG extravasation, a concomitant loss in protein
      expression of occludin, ZO-1 and ZO-2, as well as decreased and disrupted
      patterns of occludin and ZO-1 immunostaining were observed in the medial thalamus
      of thiamine-deficient mice. MMP-9 levels were also selectively increased in the
      medial thalamus of these animals, and were found to be localized in the vascular
      endothelium, as well as in cells with an apparent polymorphonuclear morphology.
      No changes of TJ gene expression were observed. These results indicate that
      alterations in TJ proteins occur in TD, and offer a plausible explanation for the
      selective increase in BBB permeability in thiamine-deficient animals. They also
      suggest a role for MMP-9 in the initiation of changes to BBB integrity in TD.

PMID- 19576515
TI  - Glutamate-dependent phosphorylation of the mammalian target of rapamycin (mTOR)
      in Bergmann glial cells.
AB  - Glutamate, the major excitatory neurotransmitter in the mammalian central nervous
      system, plays an important role in neuronal development and synaptic plasticity.
      It activates a variety of signaling pathways that regulate gene expression at the
      transcriptional and translational levels. Within glial cells, besides
      transcription, glutamate also regulates translation initiation and elongation.
      The mammalian target of rapamycin (mTOR), a key participant in the translation
      process, represents an important regulatory locus for translational control.
      Therefore, in the present communication we sought to characterize the mTOR
      phosphorylation pattern after glutamate treatment in chick cerebellar Bergmann
      glia primary cultures. A time- and dose-dependent increase in mTOR Ser 2448
      phosphorylation was found. Pharmacological tools established that the glutamate
      effect is mediated through ionotropic and metabotropic receptors and
      interestingly, the glutamate transporter system is also involved. The signaling
      cascade triggered by glutamate includes an increase in intracellular Ca2+ levels,
      and the activation of the p60(Src)/PI-3K/PKB pathway. These results suggest that
      glia cells participate in the activity-dependent change in the brain protein
      repertoire.

PMID- 19576516
TI  - Modification of the cytosolic regions of GABA transporter GAT1 by calpain.
AB  - Cytosolic regions of sodium dependent neurotransmitter transporters regulate
      their surface density and transporting function by interconnecting themselves
      with intracellular signaling pathways. Here we show that calpain activation in
      rat brain synaptosomes leads to cleavage of both N- and C-terminal regions of
      GABA transporter GAT1. In the C-terminal region, calpain removes a short segment
      of amino acids involved in binding of GAT1 to a high-density PDZ anchoring
      matrix. Using a protein pull-down assay, we found that C-terminal truncation of
      GAT1 results in modification of its interacting proteome in vitro. Results
      indicate that calpain activation/inhibition in GABAergic terminals may influence
      the scaffolding and surface expression of GABA transporter GAT1 under normal
      conditions or imbalance GAT1-mediated GABAergic transmission under pathological
      states.

PMID- 19576518
TI  - Release of [3H]D-aspartate induced by K+-stimulation is increased in the cervical
      spinal cord of the wobbler mouse: a model of motor neuron disease.
AB  - The Ca2+-dependent exocytotic release of [3H]D-aspartate and [3H]GABA evoked by
      15 mM KCl depolarization was studied in wobbler mice, an animal model of
      selective motor neuron degeneration in the cervical tract of the spinal cord.
      Neurotransmitters release was studied in superfusion using synaptosomes purified
      from the cervical or lumbar tract of the spinal cord. The early symptomatic stage
      (4 weeks) and the late symptomatic stage (12 weeks) of the disease were
      considered. Results showed that the KCl-induced release of [3H]D-aspartate was
      significantly increased in synaptosomes of the cervical region in wobbler mice
      with respect to healthy control mice, while the basal outflow was unchanged; this
      alteration was present both at 4 and 12 weeks. On the contrary, the KCl-induced
      release of [3H]D-aspartate from the lumbar spinal cord did not differ in wobbler
      and control mice. The KCl-induced release of [3H]GABA from cervical and lumbar
      spinal cord synaptosomes was unmodified at 4 weeks of age while it was moderately
      but significantly reduced in wobbler mice at 12 weeks, selectively in the
      cervical spinal cord. No changes in K(m) and V(max) for [3H]L-glutamate uptake
      were found in spinal cord synaptosomes from wobbler mice, compared to controls,
      both at 4 and 12 weeks of age. Taken together our data indicate the presence of
      an increased glutamate release in the affected region of spinal cord in wobbler
      mice, suggesting a possible involvement of altered glutamate homeostasis already
      in early stages of the wobbler disease, in the absence of appreciable changes in
      the uptake process.

PMID- 19576517
TI  - Differential effects of steroids on the synthesis of polyunsaturated fatty acids
      by human neuroblastoma cells.
AB  - Polyunsaturated fatty acids (PUFA) are crucial for proper functioning of cell
      membranes, particularly in brain. Biologically important PUFA include
      docosahexaenoic acid (n-3 series) and arachidonic acid (n-6 series) which can be
      formed from their respective dietary essential precursors, alpha-linolenic acid
      (ALA) and linoleic acid (LA). Steroid hormones are thought to modulate PUFA
      synthesis in humans but whether they regulate PUFA status in brain and/or in
      neural membranes is unknown. In human neuroblastoma SH-SY5Y cells, we compared
      the effect of estradiol, testosterone, and progesterone on PUFA synthesis. Cells
      were incubated with ALA and/or LA 7 microM in combination with estradiol,
      testosterone, or progesterone at 10 nM without serum. The fatty acid composition
      was determined by gas chromatography and the mRNA expression of genes involved in
      PUFA metabolism by real-time RT-PCR. Estradiol affected both the n-3 and the n-6
      PUFA conversion, the n-3 PUFA pathway being more sensitive to the estradiol
      treatment. In ALA-supplemented cells, estradiol increased while testosterone
      decreased the long-chain n-3 PUFA content (+17% and -15%, respectively) and the
      mRNA expression of the Delta5-desaturase (+11% and -9%), these two events being
      strongly correlated. Progesterone did not affect the PUFA composition. The
      positive effect of estradiol was blocked by the estrogen receptor antagonist ICI
      182,780. We conclude that steroids have differential effects on PUFA synthesis
      and that their mode of action could involve the modulation of the Delta5
      desaturase mRNA expression in neuroblastoma cells. These results help our
      understanding of the regulation of brain PUFA metabolism by steroid hormones.

PMID- 19576519
TI  - Activation of Wnt/beta-catenin/Tcf signaling pathway in human astrocytomas.
AB  - Astrocytomas are the most common form of primary brain tumors. Understanding the
      molecular basis of development and progression of astrocytomas is required to
      develop more effective therapies. Although, over activation of Wnt/beta
      catenin/Tcf pathway is a hallmark of several forms of cancer, little is known
      about its role in human astrocytomas. Here, we report the evidence that Wnt/beta
      catenin/Tcf signaling pathway is constitutively activated in astrocytic tumors.
      In the present study, human astrocytic tumors with different clinical grades were
      analyzed for mRNA expression of Dvl-1, Dvl-2, Dvl-3, beta-catenin, c-myc and
      cyclin D1 and protein levels of beta-catenin, Lef1, Tcf4, c-Myc, N-Myc, c-jun and
      cyclin D1. RT-PCR analysis demonstrated the overexpression of Dvl-3, beta
      catenin, c-myc and cyclin D1 in astrocytomas. Western blotting revealed
      upregulation of beta-catenin, Lef1, Tcf4 and their target proteins in the core
      tumor tissues in comparison to peritumor and normal brain tissues. The protein
      and mRNA levels were positively correlated with the histological malignancy.
      Cytoplasmic and nuclear accumulation of beta-catenin, nuclear localization of
      Lef1, Tcf4, c-Myc, N-Myc, c-jun and cyclin D1 were demonstrated by
      immunohistochemical staining. Our studies tend to suggest that Wnt/beta
      catenin/Tcf signaling pathway is implicated in malignancy of astrocytomas.

PMID- 19576520
TI  - Early long-term exposure with caffeine induces cross-sensitization to
      methylphenidate with involvement of DARPP-32 in adulthood of rats.
AB  - Chronic ingestion of caffeine causes dependence and sleep disturbance in children
      and adolescents. In rodents, the administration of caffeine may produce
      behavioral cross-sensitization to some psychostimulants, such as dopaminergic
      psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in
      pediatric- and adult human populations to manage the symptoms associated with
      attention-deficit hyperactivity disorder (ADHD). Previous studies have suggested
      that dopamine- and cAMP-regulated phosphoproteins of 32 kDa (DARPP-32)
      participate in the manifestation of behavioral activity following ingestion of
      caffeine or MPH. The aim of the present study was to evaluate whether long-term
      administration of low doses of caffeine in rodents during their adolescence
      induces cross-sensitization to MPH challenge in their adulthood and investigate
      the involvement of DARPP-32 in this model. Young rats (P25) consumed water or
      caffeine (0.3 g/L; mean consumption was 7.5 mg/day/kg) for 28 days. The caffeine
      consumption was then suspended for 14 days (washout period) when the animals
      received saline solution or MPH (1, 2, or 10 mg/kg) (P67) intraperitoneally. The
      locomotor activity of these rats was assessed using the open-field test,
      following which the immunocontent of DARPP-32 was evaluated in samples of their
      prefrontal cortex, striatum, or hippocampus. Rats chronically exposed to caffeine
      in their adolescent period and to inactive doses of MPH (1mg/kg) in adulthood
      showed augmented locomotor activity. The behavioral effect observed was
      accompanied by increased levels of DARPP-32 in the striatum and prefrontal cortex
      compared to control groups (saline or caffeine). However, no alteration caused by
      these treatments was noted in the hippocampus. In conclusion, chronic caffeine
      exposure induces likely long-term cross-sensitization to MPH in a DARPP-32
      dependent pathway.

PMID- 19576521
TI  - Simultaneous PKC and cAMP activation induces differentiation of human dental pulp
      stem cells into functionally active neurons.
AB  - The plasticity of dental pulp stem cells (DPSCs) has been demonstrated by several
      studies showing that they appear to self-maintain through several passages,
      giving rise to a variety of cells. The aim of the present study was to
      differentiate DPSCs to mature neuronal cells showing functional evidence of
      voltage gated ion channel activities in vitro. First, DPSC cultures were seeded
      on poly-l-lysine coated surfaces and pretreated for 48h with a medium containing
      basic fibroblast growth factor and the demethylating agent 5-azacytidine. Then
      neural induction was performed by the simultaneous activation of protein kinase C
      and the cyclic adenosine monophosphate pathway. Finally, maturation of the
      induced cells was achieved by continuous treatment with neurotrophin-3, dibutyryl
      cyclic AMP, and other supplementary components. Non-induced DPSCs already
      expressed vimentin, nestin, N-tubulin, neurogenin-2 and neurofilament-M. The
      inductive treatment resulted in decreased vimentin, nestin, N-tubulin and
      increased neurogenin-2, neuron-specific enolase, neurofilament-M and glial
      fibrillary acidic protein expression. By the end of the maturation period, all
      investigated genes were expressed at higher levels than in undifferentiated
      controls except vimentin and nestin. Patch clamp analysis revealed the functional
      activity of both voltage-dependent sodium and potassium channels in the
      differentiated cells. Our results demonstrate that although most surviving cells
      show neuronal morphology and express neuronal markers, there is a functional
      heterogeneity among the differentiated cells obtained by the in vitro
      differentiation protocol described herein. Nevertheless, this study clearly
      indicates that the dental pulp contains a cell population that is capable of
      neural commitment by our three step neuroinductive protocol.

PMID- 19576522
TI  - Sedation and analgesia in the ICU--pharmacology, protocolization, and clinical
      consequences. Preface.

PMID- 19576523
TI  - Pharmacology of commonly used analgesics and sedatives in the ICU:
      benzodiazepines, propofol, and opioids.
AB  - Opioids, benzodiazepines, and propofol remain the mainstay by which to optimize
      patient comfort and facilitate mechanical ventilation in patients who are
      critically ill. Unfortunately none of these agents share all of the
      characteristics of the ideal sedative or analgesic agent: rapid onset, rapid
      recovery, a predictable dose response, a lack of drug accumulation, and no
      toxicity. To optimize care, critical care clinicians should be familiar with the
      many pharmacokinetic, pharmacodynamic, and pharmacogenetic variables that can
      affect the safety and efficacy of these sedatives and analgesics.

PMID- 19576524
TI  - Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil,
      ketamine, volatile anesthetics, and the role of peripheral mu antagonists.
AB  - In this article, the authors discuss the pharmacology of sedative-analgesic
      agents like dexmedetomidine, remifentanil, ketamine, and volatile anesthetics.
      Dexmedetomidine is a highly selective alpha-2 agonist that provides anxiolysis
      and cooperative sedation without respiratory depression. It has organ protective
      effects against ischemic and hypoxic injury, including cardioprotection,
      neuroprotection, and renoprotection. Remifentanil is an ultra-short-acting opioid
      that acts as a mu-receptor agonist. Ketamine is a nonbarbiturate phencyclidine
      derivative and provides analgesia and apparent anesthesia with relative
      hemodynamic stability. Volatile anesthetics such as isoflurane, sevoflurane, and
      desflurane are in daily use in the operating room in the delivery of general
      anesthesia. A major advantage of these halogenated ethers is their quick onset,
      quick offset, and ease of titration in rendering the patient unconscious,
      immobile, and amnestic.

PMID- 19576525
TI  - Current sedation practices: lessons learned from international surveys.
AB  - Patient outcomes are significantly influenced by the choice of sedative and
      analgesic agents, the presence of over- or undersedation, poor pain control, and
      delirium. Individualized sedation management using sedation assessment tools,
      sedation protocols, and daily sedative interruption can improve clinical
      outcomes. Despite the publication of randomized trials and numerous guidelines,
      the uptake of proven strategies into routine practice can be slow. Surveys of
      clinicians' self-reported practice and prospective practice audits characterize
      sedation and analgesia practices and provide directions for education and future
      research. The objective of this review is to present the findings of surveys and
      practice audits, evaluating the management of sedation and analgesia in
      mechanically ventilated adults in the intensive care unit, and to summarize
      international critical care sedation practices.

PMID- 19576526
TI  - Protocolized and target-based sedation and analgesia in the ICU.
AB  - Administering sedative and analgesic medications is a cornerstone of optimizing
      patient comfort and minimizing distress, yet may lead to unintended consequences
      including delayed recovery from critical illness and slower liberation from
      mechanical ventilation. The use of structured approaches to sedation management,
      including guidelines, protocols, and algorithms can promote evidence-based care,
      reduce variation in clinical practice, and systematically reduce the likelihood
      of excessive and/or prolonged sedation. Patient-focused sedation algorithms are
      multidisciplinary, including physician, nurse, and pharmacist development and
      implementation. Key components of sedation algorithms include identification of
      goals and specific targets, use of valid and reliable tools to assess analgesia,
      agitation, and sedation, and incorporation of logical medication selection.
      Sedation protocols generally focus on a) algorithms that incorporate treating
      sedation and analgesia based upon escalation, de-escalation, or changing
      medications according to specific targets, or b) daily interruption of sedative
      and opioid analgesic infusions. Many published sedation protocols have been
      tested in controlled clinical trials, often demonstrating benefit such as shorter
      duration of mechanical ventilation, reduced ICU length of stay, and/or superior
      sedation management compared to usual care. Implementation of sedation algorithms
      in ICUs is a challenging process for which sufficient resources must be
      allocated.

PMID- 19576527
TI  - Sedation and weaning from mechanical ventilation: linking spontaneous awakening
      trials and spontaneous breathing trials to improve patient outcomes.
AB  - Liberation from mechanical ventilation is a vital treatment goal in the
      management of critically ill patients. The duration of mechanical ventilation is
      affected by strategies for ventilator weaning and sedation. The authors review
      literature on weaning from mechanical ventilation and delivery of sedation in
      critically ill patients, including current guidelines recommending the use of
      spontaneous breathing trials and spontaneous awakening trials. Implementation of
      these strategies in a wake-up-and-breathe protocol has demonstrated benefit over
      the use of spontaneous breathing trials alone.

PMID- 19576528
TI  - Altering intensive care sedation paradigms to improve patient outcomes.
AB  - Providing sedation and comfort for intensive care patients has evolved in the
      last few years. New approaches to improving outcomes for intensive care unit
      (ICU) patients include providing analgesia before adding sedation and recognizing
      dangerous adverse effects associated with sedative medications, such as prolonged
      effects of midazolam, propylene glycol toxicity with lorazepam, propofol infusion
      syndrome, the deliriogenic effects of benzodiazepines and propofol, and
      bradycardia with dexmedetomidine. There are now reliable and valid ways to
      monitor pain and delirium in ICU patients. Dexmedetomidine reduces the incidence
      of delirium, reduces the duration of mechanical ventilation, and appears to be
      cost effective.

PMID- 19576529
TI  - Sedation and sleep disturbances in the ICU.
AB  - The need for compassionate care of the critically ill often compels clinicians to
      treat these patients with pharmacologic sedation. Although patients may appear to
      be asleep under the influence of these sedating medications, the relationship
      between sleep and sedation is complex and not fully understood. These medications
      exert their effects at different points along the central nervous system's
      natural sleep pathway, leading to similarities and differences between the two
      states. This relationship is important because critically ill patients sleep
      poorly and this phenomenon has been linked to poor intensive care unit outcomes.
      Therefore, greater awareness of the effects of these medications on sleep may
      lead to sedation protocols that further improve outcomes. This article reviews
      the relationship between sedation and sleep from physiologic and clinical
      perspectives.

PMID- 19576530
TI  - Sedation & immunomodulation.
AB  - The management of critically ill patients necessitates the use of sedatives and
      analgesics to provide patient comfort and cooperation. These drugs exert profound
      effects on all organ systems, not only the central nervous system, and this
      article describes the immunologic effects of the commonly used critical care
      sedatives: propofol, the benzodiazepines, opioids, and alpha(2)-adrenoceptor
      agonists. Benzodiazepines, opioids, and possibly even propofol worsen outcome in
      animal models of infection, whereas preliminary evidence suggests that the
      alpha(2)-adrenoceptor agonist, dexmedetomidine, may improve outcomes in the
      setting of infection. Given the burden of sepsis and secondary infections in
      critical care, choice of sedation may need to be carefully considered to preserve
      immune responses in critically ill patients.

PMID- 19576531
TI  - Pharmacoeconomics of sedation in the ICU.
AB  - Despite considerable information on the pharmacotherapy of sedation in the ICU,
      there is little published on the pharmacoeconomics of sedation in patients who
      are critically ill. The purpose of this article is to discuss the various
      components that contribute to the cost of treating the agitated ICU patient and
      to critically review the articles published since 2000 that evaluated costs and
      cost-effectiveness in ICU patients receiving drugs for agitation and/or pain.
      Clinicians should look beyond the acquisition cost of a sedative and include the
      effect of sedatives on the cost of care when selecting the most appropriate
      sedative.

PMID- 19576532
TI  - Delirium prevention and treatment.
AB  - Delirium occurs in 35% to 80% of critically ill hospitalized patients. Little is
      known of delirium prevention and treatment in the critical care setting. Trials
      emphasizing early mobilization suggest that this nonpharmacologic approach is
      associated with improved outcome as well as "delirium days". Titration and
      reduction of opiate analgesics and sedatives may improve subsyndromal delirium
      rates. All critical care caregivers should rigorously screen for alcohol abuse,
      apply alcohol withdrawal scales in alcoholic patients, and titrate sedative
      drugs. No nonpharmacologic approach or drug has been shown to be beneficial once
      delirium is established. Considering the importance and the consequences of
      delirium in the critical care setting, addiction studies are urgently needed.

PMID- 19576534
TI  - Cognitive functioning, mental health, and quality of life in ICU survivors: an
      overview.
AB  - Critical illness can and often does lead to significant cognitive impairment and
      to the development of psychological disorders. These conditions are persistent
      and, although they improve with time, often fail to completely abate. Although
      the functional correlates of cognitive and psychological morbidity (depression,
      anxiety, and posttraumatic stress disorder) have been studied, they may include
      poor quality of life, inability to return to work or to work at previously
      established levels, and inability to function effectively in emotional and
      interpersonal domains. The potential etiologies of cognitive impairment and
      psychological morbidity in ICU survivors are particularly poorly understood and
      may vary widely across patients. Potential contributors may include the
      potentially toxic effects of sedatives and narcotics, delirium, hypoxia, glucose
      dysregulation, metabolic derangements, and inflammation. Patients with
      preexisting vulnerabilities, including predisposing genetic factors, and frail
      elderly populations may be at particular risk for emergence of acceleration of
      conditions such as mild cognitive impairment.

PMID- 19576533
TI  - Delirium: an emerging frontier in the management of critically ill children.
AB  - The objectives of this article are (1) to introduce pediatric delirium and
      provide understanding of acute brain dysfunction with its classification and
      clinical presentations (2) to understand how delirium is diagnosed and discuss
      current modes of delirium diagnosis in the critically ill adult population and
      translation to pediatrics (3) to understand the prevalence and prognostic
      significance of delirium in the adult and pediatric critically ill population (4)
      to discuss the pathophysiology of delirium as currently understood, and (5) to
      provide general management guidelines for delirium.

PMID- 19576535
TI  - Number of 24-hour diet recalls needed to estimate energy intake.
AB  - PURPOSE: Twenty-four-hour diet recall interviews (24HRs) are used to assess diet
      and to validate other diet assessment instruments. Therefore it is important to
      know how many 24HRs are required to describe an individual's intake. METHOD:
      Seventy-nine middle-aged white women completed seven 24HRs over a 14-day period,
      during which energy expenditure (EE) was determined by the doubly labeled water
      method (DLW). Mean daily intakes were compared to DLW-derived EE using paired t
      tests. Linear mixed models were used to evaluate the effect of call sequence and
      day of the week on 24HR-derived energy intake while adjusting for education,
      relative body weight, social desirability, and an interaction between call
      sequence and social desirability. RESULTS: Mean EE from DLW was 2115 kcal/day.
      Adjusted 24HR-derived energy intake was lowest at call 1 (1501 kcal/day);
      significantly higher energy intake was observed at calls 2 and 3 (2246 and 2315
      kcal/day, respectively). Energy intake on Friday was significantly lower than on
      Sunday. Averaging energy intake from the first two calls better approximated true
      energy expenditure than did the first call, and averaging the first three calls
      further improved the estimate (p=0.02 for both comparisons). Additional calls did
      not improve estimation. CONCLUSIONS: Energy intake is underreported on the first
      24HR. Three 24HRs appear optimal for estimating energy intake.

PMID- 19576536
TI  - Main source of drinking water and familial aggregation of Kashin-Beck disease: a
      population based on case-control family study.
AB  - PURPOSE: Kashin-Beck disease (KBD) is an osteoarthropathy affecting 2.5 million
      of 30 million residents of China's KBD-endemic regions. This study assesses the
      etiologic role of river water as a main source of drinking water, its impact on
      and interaction with KBD familial aggregation. METHODS: From 2006-2007, we
      conducted a population-based case-control study of familial KBD in Linyou County,
      Shaanxi Province, China. Study subjects included 212 case families (1,951
      individuals) and 212 control families (1,897 individuals). Using conditional
      logistic regression to analyze case-control data and second-order generalized
      estimating equation (GEE2) to examine family data, we adjusted for age and gender
      in all marginal regression analyses. RESULTS: The odds ratio (OR) for river water
      intake's association with KBD was 5.97 (95% confidence interval [CI]), 3.32
      10.72). Compared with relatives of controls, proband relatives had a higher risk
      of disease, with a conditional OR = 2.35 (95% CI, 1.05-5.24). When river water
      was controlled in the analyses, association parameters among first- and second
      degree relatives were no longer statistically significant. CONCLUSION: Collective
      river water intake among relatives was likely and predominantly responsible for
      familial KBD aggregation in southwestern China.

PMID- 19576537
TI  - Identifying HIV risk-reduction strategies for Hispanic populations in Broward
      County.
AB  - PURPOSE: To improve the effectiveness of behavioral interventions for Hispanic
      young adults, we studied their perceived risks for HIV infection, lifetime and
      more recent sexual experiences, use of condoms, and HIV-antibody testing
      histories. METHODS: Logistic regression was used to analyze computer-assisted
      telephone-interview surveys of 1,596 randomly selected Hispanic residents of 12
      high AIDS-incidence ZIP-code areas. RESULTS: After we controlled for gender, age,
      marital status, educational attainment, and language of preference, differences
      were found by country of origin. Those coming from Peru (adjusted odds ratio
      [AOR]=3.45; 95%CI=1.85-6.43) and Colombia (AOR=1.94; 95%CI=1.12-3.36) were more
      likely than U.S.-native Hispanics to perceive their risk of acquiring HIV as
      above average. Sexually active Mexicans (AOR=1.80; 95%CI=1.04-3.10) were
      significantly more likely than U.S. natives to have used a condom in the past 12
      months. Young adults coming from Puerto Rico (AOR=0.55; 95%CI=0.33-0.91) were
      less likely than U.S.-native Hispanics to have ever been tested for HIV.
      Virginity and sexual abstinence were unrelated to country of origin, but
      respondents interviewed in Spanish were more likely than those interviewed in
      English to be sexually active (AOR=2.57; 95%=1.39-4.75). CONCLUSIONS: To maximize
      the impact of behavioral interventions, risk-reduction programs must adjust for
      social and cultural differences within the Hispanic-American population.

PMID- 19576538
TI  - Factorial invariance of child self-report across race/ethnicity groups: a
      multigroup confirmatory factor analysis approach utilizing the PedsQL 4.0 Generic
      Core Scales.
AB  - PURPOSE: In order to compare health-related quality of life (HRQOL) research
      findings across race/ethnicity subpopulations, it is important to demonstrate
      factorial invariance, i.e., that the items have equivalent meaning across the
      race/ethnicity groups studied. This study examined the factorial invariance of
      child self-reported HRQOL across race/ethnicity groups for ages 5-18 years
      utilizing the 23-item PedsQL 4.0 Generic Core Scales. METHODS: Multigroup
      confirmatory factor analysis (CFA) was performed, specifying a five-factor model
      across four race/ethnicity groups (White Non-Hispanic, Hispanic, Asian/Pacific
      Islander, Black Non-Hispanic). Multigroup structural equation models were
      proposed in order to compare the factor structure across the four race/ethnicity
      subpopulations. The analyses were based on 5,490 children recruited from clinic,
      school, and community populations. RESULTS: Strict factorial invariance across
      the four race/ethnicity groups was demonstrated based on stability of the
      Comparative Fit Index (CFI) between the models, and several additional indices of
      practical fit including the Root Mean Squared Error of Approximation (RMSEA), the
      Non-Normed Fit Index (NNFI), and the Parsimony Normed Fit Index (PNFI).
      CONCLUSIONS: The findings support an equivalent five-factor structure across the
      four race/ethnicity subpopulations studied. Based on these data, it can be
      concluded that children across the four race/ethnicity groups studied interpreted
      items in a similar manner regardless of their race/ethnicity.

PMID- 19576539
TI  - No relationship between body mass index during adolescence and all-cause
      mortality in Japanese women--a 56.5-year observational study.

PMID- 19576540
TI  - Risk of classic Kaposi sarcoma with residential exposure to volcanic and related
      soils in Sicily.
AB  - PURPOSE: Before AIDS, endemic (African) Kaposi sarcoma (KS) was noted to occur in
      volcanic areas and was postulated to result from dirt chronically embedded in the
      skin of the lower extremities. The primary cause of all KS types is KS-associated
      herpesvirus (KSHV) infection, but cofactors contribute to the neoplasia. We
      investigated whether residential exposure to volcanic or related soils was
      associated with the risk of classic Kaposi sarcoma (cKS) in Sicily. METHODS: Risk
      of incident cKS (N=141) compared with population-based KSHV seropositive controls
      (N=123) was estimated for residential exposure to four types of soil, categorized
      with maps from the European Soil Database and direct surveying. Questionnaire
      data provided covariates. RESULTS: Residents in communities high in luvisols were
      approximately 2.7 times more likely to have cKS than those in communities with no
      luvisols. Risk was not specific for cKS on the limbs, but it was elevated
      approximately four- to five-fold with frequent bathing or tap water drinking in
      communities with high luvisols. Risk was unrelated to communities high in
      andosols, tephra, or clay soils. CONCLUSIONS: Iron and alumino-silicate clay,
      major components of luvisols, may increase cKS risk, but formal investigation and
      consideration of other soil types and exposures are needed.

PMID- 19576541
TI  - Impermanence.

PMID- 19576542
TI  - Coming to terms with a diagnosis of HIV in Iran: a phenomenological study.
AB  - The number of people living with HIV (PLWH) has increased in all Asian regions,
      including Iran. Discovering that one has any serious illness can be a traumatic
      experience, but coming to terms with an HIV diagnosis is made more difficult by
      social constructs and negative reactions to the infection. This interpretative
      phenomenological study was carried out to understand and describe the lived
      experience of HIV-infected Iranians during the period immediately following an
      HIV diagnosis. Audiotaped in-depth semistructured interviews with 13 participants
      were used to collect data, which were analyzed with critical hermeneutics. Two
      main themes emerged: (a) doubt and delay in coming to terms with the diagnosis
      and (b) testing and its associated impacts. Nine subthemes were also found. Many
      challenges face people who need to determine their HIV status, and these are
      compounded by the sociocultural context found in Iran. Iran needs more education,
      counseling, testing facilities, and support programs to encourage people to get
      tested for HIV and to help them deal with a positive test result.

PMID- 19576543
TI  - HIV infection and obesity: a review of the evidence.
AB  - This article provides a review of recent evidence pertinent to the prevalence,
      morbidities, and predictive value of overweight and obesity in PLWH. Implications
      for clinical outcomes are discussed, and recommendations for patient management
      and future research are advanced.

PMID- 19576545
TI  - The effect of prevention messages and self-efficacy skill building with inner
      city women at risk for HIV infection.
AB  - The purpose of this study was to examine the effect of gender-sensitive and
      culturally relevant HIV prevention film messages combined with self-efficacy and
      skill building exercises on self-reported safe sex behaviors, intentions,
      attitudes, and self-advocacy over time. A sample of 131 women of mixed ethnicity
      from inner-city Boston who were living in transitional housing participated in a
      4-week pre/postmeasurement design. Results showed that, despite the short
      duration of the intervention, participants self-reported significantly more use
      of safe sex behaviors and being prepared for sexual intimacy after the
      intervention. The study validated use of an approach originally intended for
      African American women with other women at risk for HIV.

PMID- 19576544
TI  - Knowing kids dying of HIV: a traumatic event for AIDS orphans.
AB  - Data from 755 AIDS orphans living in a rural area of China with high rates of HIV
      infection were used to examine the association between a child's trauma symptoms
      and knowing a peer with HIV infection or one who had died of HIV. Trauma symptoms
      were measured by the Traumatic Symptoms Checklist for Children-Chinese Version
      (TSCC-CV). About 47% of participants reported they knew a child with HIV or one
      who had died of HIV. More orphans living in family-based care reported such
      knowledge, and trauma symptoms were significantly higher in children who reported
      such knowledge. Multivariate analysis showed that such knowledge was
      significantly associated with traumatic symptoms, controlling for gender, age,
      family socioeconomic status, orphan status (double vs. single), and care
      arrangement (family-based vs. institutional care). The results underscored the
      importance of psychosocial support and counseling to orphans in communities with
      high levels of HIV-related mortality.

PMID- 19576546
TI  - Impact of a peer-group intervention on occupation-related behaviors for urban
      hospital workers in Malawi.
AB  - Using a pre- and posttest design with no control group, the authors evaluated the
      impact of a peer-group intervention on work related knowledge and behavior for
      health workers at an urban hospital in Malawi. The authors surveyed unmatched
      random samples of health workers, observed workers on the job, and interviewed
      clients about hospital services at baseline and at 6 months after the
      intervention. Universal precautions knowledge, reported hand washing, and
      reported client teaching were significantly higher at the final evaluation. The
      outcome differences remained robust in multivariate analyses with controls for
      demographic factors of age, gender, education, food security, and job category.
      Observations reported consistently greater use of universal precautions, more
      respectful interactions, and more client teaching at final evaluation. Patient
      surveys reported more discussion with health workers about HIV at the final
      evaluation. Peer-group interventions can prepare health workers in Malawi for HIV
      prevention and offer a potential model for other African countries.

PMID- 19576548
TI  - Telephone nurse counseling improves HIV medication adherence: an effectiveness
      study.
AB  - Antiretroviral therapy remains a challenge for persons living with HIV (PLWH),
      who must maintain high levels of adherence to prevent viral resistance and
      treatment failure. This effectiveness study examined a telephonic nursing program
      to translate well-validated cognitive-behavioral and motivational interviewing
      adherence counseling into routine clinical care. Participants were 98 PLWH who
      were followed for up to 6 months after recruitment from HIV care settings across
      the United States. Each participant received telephone counseling (Mdn =three
      sessions) from a trained nurse who followed up with the participant over time.
      Nurses assessed participants' readiness for adherence, provided support to
      overcome identified barriers, and offered information based on participants'
      questions. At 6 months after the start of treatment, a greater percentage of
      participants had adherence at or above 95% than expected for this population,
      based on a clinical interview. Self-efficacy was related to baseline medication
      adherence, whereas other clinical and demographic variables were not. Attrition
      was a concern but was unrelated to adherence, self-efficacy, or clinical severity
      measures. Telephone counseling was associated with a relatively high percentage
      of participants reaching target antiretroviral therapy adherence levels and may
      be an effective method to disseminate psychologically based counseling into a
      broad range of care settings.

PMID- 19576547
TI  - Risk of sexual HIV transmission among wives left behind and wives of nonmigrant
      men in rural areas of China.
AB  - In rural areas of China where commercial plasma donation used to be common,
      little is known about sexual behaviors and condom use among wives left behind by
      migrating husbands and wives of nonmigrant men. This study investigated sexual
      behaviors and condom use among married women in rural areas of China. A cross
      sectional survey was conducted with 1,873 participants recruited by a cluster
      sampling method. Study results showed that wives left behind had a significantly
      lower mean frequency of sexual intercourse with their husbands in the previous
      month, a higher rate of multiple sexual partners, a higher rate of self-reported
      HIV infection, and a lower rate of condom use when compared with wives of
      nonmigrant men. Also, HIV-infected wives left behind who were infected by their
      husbands had multiple sex partners and did not use condoms consistently. This
      research provides additional insight that may be used to develop effective HIV
      prevention strategies in rural areas of China.

PMID- 19576549
TI  - Selenium supplementation in HIV-infected patients: is there any potential
      clinical benefit?
AB  - In HIV-infected patients undergoing antiretroviral therapy, the question of
      whether selenium supplementation has any therapeutic benefit is still open. With
      recent popular coverage of this issue, many patients have considered using
      selenium. Clinicians have a duty to ensure that the recommendations they make to
      their patients are evidence based. The literature search reported here showed
      that evidence to support standard selenium supplementation in patients with HIV
      is both limited and insufficient. To definitively answer this clinical question,
      the overall effect of selenium supplementation would need to be evaluated in a
      large randomized, controlled trial with solid methodology and strong internal
      validity. Although the available evidence for selenium supplementation is weak,
      its low toxicity and side effect profile seem to pose minimal risks, especially
      at low doses. For patients who want to add selenium to their regimen, discussing
      the potential risks and benefits as well as close follow-up is warranted.

PMID- 19576550
TI  - The third epoch: "kidney plus" transplantation.

PMID- 19576551
TI  - Kidney failure in the shadows of "vital" organ disease.

PMID- 19576552
TI  - Kidney transplantation: the ideal immunosuppression regimen.
AB  - Kidney transplantation today has excellent short-term outcomes, but long-term
      graft survival has not improved in a parallel fashion. The goal of
      immunosuppressive therapy is to balance the beneficial effects of reducing acute
      rejection while minimizing adverse effects from oversuppression including the
      development of infections, malignancy, and cardiovascular risk factors. In
      general, current immunosuppressive protocols use combinations of
      immunosuppressive agents with different mechanisms of action to maximize efficacy
      and minimize the toxicity of each drug. During the past decade, there has been a
      growing interest in identifying regimens that permit the minimization of
      calcineurin inhibitors or corticosteroids in an attempt to decrease
      nephrotoxicity and metabolic side effects. The emergence of new immunosuppressive
      agents and tolerance protocols appear promising as a means to deliver
      immunosuppression without long-term toxicity. Ultimately, the goal of prescribing
      immunosuppression is to transition from empiric therapy to one of individualized
      therapy.

PMID- 19576553
TI  - The epidemiology and prevention of donor-derived infections.
AB  - Donor-derived infectious diseases are infections that are present in an organ
      donor and have the potential to be transmitted to at least 1 transplant
      recipient. Several recent transmissions have been covered by the lay media and in
      the medical literature, including a recent transmission of HIV and hepatitis C
      virus from 1 donor to 4 recipients. These reports have highlighted the importance
      and clinical impact of this rare complication of organ transplantation. Donor
      derived infectious diseases appear to complicate less than 1% of all transplant
      procedures, but, when a transmission occurs, significant morbidity and mortality
      can occur. A number of guidelines and policies define the optimal screening of
      organ donors to prevent the transmission of infectious diseases. Unfortunately,
      there are significant limitations in our screening methods, and only some
      pathogens are screened for routinely. The regulatory framework related to and the
      epidemiology, identification, and management of donor-derived infectious disease
      transmission shall be reviewed.

PMID- 19576554
TI  - Living kidney donors: current state of affairs.
AB  - Living kidney donation continues as the cornerstone of transplantation. In order
      to determine with ever-renewing assurance that living donation is safe for the
      donor, we need to periodically review the literature, review the United Network
      for Organ Sharing database for donor characteristics that may put them in danger,
      and scour databases for donors starting dialysis and/or listed for transplant.
      Additionally, we must encourage financing studies that follow large diverse
      cohorts of donors over their entire lifetimes in order to detect key
      characteristics that influence outcomes. Currently, it can be stated that living
      donation is, on the whole, safe, with few perioperative deaths, complications, or
      long-term medical issues. Additionally, the living donor reflects the
      demographics of the general population including increased rates of obesity with
      some donors having hypertension and low-grade proteinuria. In the long run, death
      rates (for the white donor) are no different than for the general population,
      whereas end-stage renal disease rates are slightly increased over the general
      population, ranging from 0.1% to 1.1%. The higher risk is especially notable in
      the black donor. Preeclampsia in female donors may also be marginally greater
      than in those with 2 kidneys. Thus, the new health age brings a rejuvenated
      responsibility of the medical community and those in governance to design systems
      that allow more complete and continued follow-up of the living kidney donor,
      especially those of color.

PMID- 19576555
TI  - Renal replacement therapy in the liver transplant candidate.
AB  - Since the implementation of the model of end-stage liver disease score to
      prioritize patients for orthotopic liver transplantation (OLT), the number of
      liver transplant candidates with renal failure and on renal replacement therapy
      (RRT) has dramatically increased. This review is intended to discuss the
      indications and implications of RRT initiation, the different RRT modalities, and
      special problems encountered with RRT in OLT candidates.

PMID- 19576556
TI  - Acute kidney injury after liver, heart, and lung transplants: dialysis modality,
      predictors of renal function recovery, and impact on survival.
AB  - Recipients of nonrenal organ transplants including the liver, heart, and lung are
      at risk for developing acute kidney injury (AKI) and chronic kidney disease
      (CKD). Underlying hepatic or cardiopulmonary failure, prolonged intraoperative
      hemodynamic instability, and the use of calcineurin inhibitors and nephrotoxic
      medications have all been suggested to be contributory. The incidence of
      perioperative AKI has been reported to occur in 17% to 95% in liver transplant
      recipients, 5% to 30% in heart transplant recipients, and 5% to 60% in recipients
      of lung transplants. Among those who develop AKI, renal replacement therapy is
      required in 5% to 35%, 5% to 15%, and 8% to 10% in liver, heart, and lung
      transplant recipients, respectively. The current article presents an overview of
      the literature on the choice of dialysis modality and its associated advantages
      and disadvantages in the management of AKI after liver, heart, and lung
      transplants. Predictive factors for renal function recovery and the impact of AKI
      and CKD on survival will also be discussed.

PMID- 19576557
TI  - Simultaneous liver-kidney transplantation in the MELD era.
AB  - Impaired kidney function is common in liver transplant candidates and portends
      heightened risk for both postoperative chronic kidney disease and mortality. The
      weighting of serum creatinine in the Model of End-stage Liver Disease
      classification for liver allocation has been accompanied by a proliferation of
      simultaneous liver-kidney transplants in recent years. In the absence of
      standardized criteria for allocating kidneys in this setting, there is a wide
      variation in combined organ transplants across transplant centers. This review
      discusses the issues surrounding simultaneous liver-kidney transplantation and
      proposes a strategy for selecting patients to receive both organs.

PMID- 19576559
TI  - Combined heart-kidney transplantation: a review of recipient selection and
      patient outcomes.
AB  - Elevated serum creatinine is a common finding among patients awaiting heart
      transplantation because of reduced renal perfusion in the setting of severe heart
      failure as well as overlapping risk factors for chronic kidney disease and heart
      disease. Patients with significant renal dysfunction preoperatively have worse
      outcomes with heart transplantation alone compared with those with normal renal
      function or those with renal dysfunction who undergo combined heart-kidney
      transplantation. Optimizing organ distribution and patient outcomes after cardiac
      transplantation requires appropriate recipient selection, including deciding
      which patients will benefit from combined heart-kidney transplantation. This
      review focuses on the evaluation of patients with chronic kidney disease awaiting
      heart transplantation and the outcomes of combined heart-kidney transplantation.

PMID- 19576558
TI  - Simultaneous pancreas kidney transplantation: a critical appraisal of the risks
      and benefits compared with other treatment alternatives.
AB  - Advances in technical aspects of pancreas transplantation and improvements in
      immunosuppression over the last decade have led to significant improvements in
      pancreas transplant outcomes in the short-term. Simultaneous kidney pancreas
      transplantation remains an attractive option for patients with type 1 diabetes
      (T1DM) and late chronic kidney disease (CKD), with 1-year pancreas graft survival
      rates of 86% in 2004. For the individual patient with T1DM and CKD, the various
      transplant options must be considered carefully, with attention to the timing of
      surgery relative to the need for dialysis, the challenge in managing diabetes
      with noninvasive medical therapy, and the assumption of risks attendant to each
      surgical option. This review summarizes the current status of simultaneous
      pancreas kidney transplantation and compares and contrasts outcomes with other
      potential treatment options.

PMID- 19576560
TI  - [Monitoring the quality of life of end-stage renal disease patients. Quality of
      life report - REIN - Dialysis 2005].

PMID- 19576561
TI  - Identification and characterization of novel immunogenic outer membrane proteins
      of Haemophilus parasuis serovar 5.
AB  - Haemophilus parasuis is the aetiological agent of Glasser's disease, which is
      responsible for cases of fibrinous polyserositis, polyarthritis and meningitis in
      young pigs. To develop more effective vaccines, an immunoproteome-based approach
      was used to analyze the outer membrane proteins of H. parasuis serovar 5. A total
      of 15 proteins with high immunogenicity were identified and all were showed to be
      immunogens for the first time in H. parasuis. Further analyses of 8 selected
      proteins revealed that (1) significantly higher level of serum antibodies against
      6 proteins was detected with convalescent sera and immunized sera; (2) antisera
      against 5 of the selected proteins could effectively inhibit H. parasuis growth
      in mouse blood; and (3) 4 proteins could induce protective response of the
      vaccinated mice against H. parasuis. The results suggest these 4 proteins (PalA,
      Omp2, D15 and HPS_06257) have strong potential to be vaccine candidates.

PMID- 19576562
TI  - Dynamic adjustment of temporal preparation: shifting warning signal modality
      attenuates the sequential foreperiod effect.
AB  - We examined sequential effects in the variable foreperiod (FP) paradigm, which
      refer to the finding that responses to an imperative signal (IS) are fast when a
      short FP trial is repeated but slow when it is preceded by a long FP trial. The
      effect has been attributed to a trace-conditioning mechanism in which individuals
      learn the temporal relationship between a warning signal (WS) and the IS in a
      trial-by-trial manner. An important assumption is that the WS in a current trial
      (i.e., trial FP(n)) acts as a conditioned stimulus, such that it automatically
      triggers the conditioned response at the exact critical moment that was
      imperative in the previous trial (i.e., trial FP(n-1)). According to this
      assumption, a shift from one WS modality in trial FP(n-1) to another modality in
      trial FP(n) is expected to eliminate or at least reduce the sequential FP effect.
      This prediction was tested in three experiments that included a random variation
      of WS modality and FP length within blocks of trials. In agreement with the
      prediction, a shift in WS modality attenuated the asymmetry of the sequential FP
      effect.

PMID- 19576563
TI  - Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa
      type 2.
AB  - Autosomal-recessive cutis laxa type 2 (ARCL2) is a multisystem disorder
      characterized by the appearance of premature aging, wrinkled and lax skin, joint
      laxity, and a general developmental delay. Cutis laxa includes a family of
      clinically overlapping conditions with confusing nomenclature, generally
      requiring molecular analyses for definitive diagnosis. Six genes are currently
      known to mutate to yield one of these related conditions. We ascertained a cohort
      of typical ARCL2 patients from a subpopulation isolate within eastern Canada.
      Homozygosity mapping with high-density SNP genotyping excluded all six known
      genes, and instead identified a single homozygous region near the telomere of
      chromosome 17, shared identically by state by all genotyped affected individuals
      from the families. A putative pathogenic variant was identified by direct DNA
      sequencing of genes within the region. The single nucleotide change leads to a
      missense mutation adjacent to a splice junction in the gene encoding pyrroline-5
      carboxylate reductase 1 (PYCR1). Bioinformatic analysis predicted a pathogenic
      effect of the variant on splice donor site function. Skipping of the associated
      exon was confirmed in RNA from blood lymphocytes of affected homozygotes and
      heterozygous mutation carriers. Exon skipping leads to deletion of the reductase
      functional domain-coding region and an obligatory downstream frameshift. PYCR1
      plays a critical role in proline biosynthesis. Pathogenicity of the genetic
      variant in PYCR1 is likely, given that a similar clinical phenotype has been
      documented for mutation carriers of another proline biosynthetic enzyme,
      pyrroline-5-carboxylate synthase. Our results support a significant role for
      proline in normal development.

PMID- 19576564
TI  - Gene conversion between the X chromosome and the male-specific region of the Y
      chromosome at a translocation hotspot.
AB  - Outside the pseudoautosomal regions, the mammalian sex chromosomes are thought to
      have been genetically isolated for up to 350 million years. However, in humans
      pathogenic XY translocations occur in XY-homologous (gametologous) regions,
      causing sex-reversal and infertility. Gene conversion might accompany
      recombination intermediates that resolve without translocation and persist in the
      population. We resequenced X and Y copies of a translocation hotspot adjacent to
      the PRKX and PRKY genes and found evidence of historical exchange between the
      male-specific region of the human Y and the X in patchy flanking gene-conversion
      tracts on both chromosomes. The rate of X-to-Y conversion (per base per
      generation) is four to five orders of magnitude more rapid than the rate of Y
      chromosomal base-substitution mutation, and given assumptions about the
      recombination history of the X locus, tract lengths have an overall average
      length of approximately 100 bp. Sequence exchange outside the pseudoautosomal
      regions could play a role in protecting the Y-linked copies of gametologous genes
      from degeneration.

PMID- 19576565
TI  - Deficiency of Dol-P-Man synthase subunit DPM3 bridges the congenital disorders of
      glycosylation with the dystroglycanopathies.
AB  - Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important
      subgroup of the muscular dystrophies that have been related to defective O
      mannosylation of alpha-dystroglycan. In many patients, the underlying genetic
      etiology remains unsolved. Isolated muscular dystrophy has not been described in
      the congenital disorders of glycosylation (CDG) caused by N-linked protein
      glycosylation defects. Here, we present a genetic N-glycosylation disorder with
      muscular dystrophy in the group of CDG type I. Extensive biochemical
      investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man)
      synthase activity. Sequencing of the three DPM subunits and complementation of
      DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the
      strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the
      ER membrane. Cotransfection experiments in CHO cells showed a reduced binding
      capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent
      glycosylation pathways in the ER revealed strongly reduced O-mannosylation of
      alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype
      of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3
      mutations is a cause for alpha-dystroglycanopathy, thereby bridging the
      congenital disorders of glycosylation with the dystroglycanopathies.

PMID- 19576566
TI  - PRKCA: a positional candidate gene for body mass index and asthma.
AB  - Asthma incidence and prevalence are higher in obese individuals. A potential
      mechanistic basis for this relationship is pleiotropy. We hypothesized that
      significant linkage and candidate-gene association would be found for body mass
      index (BMI) in a population ascertained on asthma affection status. Linkage
      analysis for BMI was performed on 657 subjects in eight Costa Rican families
      enrolled in a study of asthma. Family-based association studies were conducted
      for BMI with SNPs within a positional candidate gene, PRKCA. SNPs within PRKCA
      were also tested for association with asthma. Association studies were conducted
      in 415 Costa Rican parent-child trios and 493 trios participating in the
      Childhood Asthma Management Program (CAMP). Although only modest evidence of
      linkage for BMI was obtained for the whole cohort, significant linkage was noted
      for BMI in females on chromosome 17q (peak LOD = 3.39). Four SNPs in a candidate
      gene in this region (PRKCA) had unadjusted association p values < 0.05 for BMI in
      both cohorts, with the joint p value for two SNPs remaining significant after
      adjustment for multiple comparisons (rs228883 and rs1005651, joint p values = 9.5
      x 10(-)(5) and 5.6 x 10(-)(5)). Similarly, eight SNPs had unadjusted association
      p values < 0.05 for asthma in both populations, with one SNP remaining
      significant after adjustment for multiple comparisons (rs11079657, joint p value
      = 2.6 x 10(-)(5)). PRKCA is a pleiotropic locus that is associated with both BMI
      and asthma and that has been identified via linkage analysis of BMI in a
      population ascertained on asthma.

PMID- 19576568
TI  - Genome-wide study of families with absolute pitch reveals linkage to 8q24.21 and
      locus heterogeneity.
AB  - Absolute pitch (AP) is the rare ability to instantaneously recognize and label
      tones with their musical note names without using a reference pitch for
      comparison. The etiology of AP is complex. Prior studies have implicated both
      genetic and environmental factors in its genesis, yet the molecular basis for AP
      remains unknown. To locate regions of the human genome that may harbor AP
      predisposing genetic variants, we performed a genome-wide linkage study on 73
      multiplex AP families by genotyping them with 6090 SNP markers. Nonparametric
      multipoint linkage analyses were conducted, and the strongest evidence for
      linkage was observed on chromosome 8q24.21 in the subset of 45 families with
      European ancestry (exponential LOD score = 3.464, empirical genome-wide p =
      0.03). Other regions with suggestive LOD scores included chromosomes 7q22.3,
      8q21.11, and 9p21.3. Of these four regions, only the 7q22.3 linkage peak was also
      evident when 19 families with East Asian ancestry were analyzed separately.
      Though only one of these regions has yet reached statistical significance
      individually, we detected a larger number of independent linkage peaks than
      expected by chance overall, indicating that AP is genetically heterogeneous.

PMID- 19576567
TI  - Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39.
AB  - A gene causing autosomal-recessive, nonsyndromic hearing loss, DFNB39, was
      previously mapped to an 18 Mb interval on chromosome 7q11.22-q21.12. We mapped an
      additional 40 consanguineous families segregating nonsyndromic hearing loss to
      the DFNB39 locus and refined the obligate interval to 1.2 Mb. The coding regions
      of all genes in this interval were sequenced, and no missense, nonsense, or
      frameshift mutations were found. We sequenced the noncoding sequences of genes,
      as well as noncoding genes, and found three mutations clustered in intron 4 and
      exon 5 in the hepatocyte growth factor gene (HGF). Two intron 4 deletions occur
      in a highly conserved sequence that is part of the 3' untranslated region of a
      previously undescribed short isoform of HGF. The third mutation is a silent
      substitution, and we demonstrate that it affects splicing in vitro. HGF is
      involved in a wide variety of signaling pathways in many different tissues, yet
      these putative regulatory mutations cause a surprisingly specific phenotype,
      which is nonsydromic hearing loss. Two mouse models of Hgf dysregulation, one in
      which an Hgf transgene is ubiquitously overexpressed and the other a conditional
      knockout that deletes Hgf from a limited number of tissues, including the
      cochlea, result in deafness. Overexpression of HGF is associated with progressive
      degeneration of outer hair cells in the cochlea, whereas cochlear deletion of Hgf
      is associated with more general dysplasia.

PMID- 19576570
TI  - Regarding "Eagle-eyed visual acuity: an experimental investigation of enhanced
      perception in autism".

PMID- 19576571
TI  - Low cerebrospinal fluid neuropeptide Y concentrations in posttraumatic stress
      disorder.
AB  - BACKGROUND: Neuropeptide Y (NPY), a peptide neurotransmitter that regulates
      stress and anxiety, has been proposed to be a stress resilience factor in humans.
      Posttraumatic stress disorder (PTSD) is a stress-related anxiety disorder. We
      hypothesized that central nervous system NPY is dysregulated in PTSD and sought
      to redress the absence of central NPY data in the disorder. METHODS: We
      determined morning NPY concentrations in cerebrospinal fluid (CSF) from 10 male
      subjects with chronic combat-related PTSD and from 13 healthy men. Neuropeptide Y
      like immunoreactivity was measured by enzyme immunoassay (EIA). RESULTS: As
      compared with the normal comparison subjects, PTSD patients had significantly
      lower concentrations of CSF neuropeptide Y (mean CSF NPY was 360.0 +/- 17.7 pg/mL
      in control subjects but only 233.6 +/- 28.7 pg/mL in PTSD patients [p = .0008]).
      Adjustments for age and body mass index (BMI) still revealed a highly significant
      reduction in CSF NPY in the PTSD group (p = .003). CONCLUSIONS: Men with combat
      related PTSD have low CSF concentrations of the putative resiliency hormone NPY,
      possibly related to the disorder or to extreme stress exposure per se.

PMID- 19576569
TI  - Diverse evolutionary histories for beta-adrenoreceptor genes in humans.
AB  - In humans, three genes--ADRB1, ADRB2 and ADRB3--encode beta-adrenoreceptors
      (ADRB); these molecules mediate the action of catecholamines in multiple tissues
      and play pivotal roles in cardiovascular, respiratory, metabolic, and
      immunological functions. Genetic variants in ADRB genes have been associated with
      widespread diseases and conditions, but inconsistent results have often been
      obtained. Here, we addressed the recent evolutionary history of ADRB genes in
      human populations. Although ADRB1 is neutrally evolving, most tests rejected
      neutral evolution for ADRB2 in European, African, and Asian population samples.
      Analysis of inferred haplotypes for ADRB2 revealed three major clades with a
      coalescence time of 1-1.5 million years, suggesting that the gene is either
      subjected to balancing selection or undergoing a selective sweep. Haplotype
      analysis also revealed ethnicity-specific differences. Additionally, we observed
      significant deviations from Hardy-Weinberg equilibrium (HWE) for ADRB2 genotypes
      in distinct European cohorts; HWE deviation depends on sex (only females are in
      disequilibrium), and genotypes displaying maximum and minimum relative fitness
      differ across population samples, suggesting a complex situation possibly
      involving epistasis or maternal selection. Overall, our data indicate that future
      association studies involving ADRB2 will benefit from taking into account
      ethnicity-specific haplotype distributions and sex-based effects. With respect to
      ADRB3, our data indicate that the gene has been subjected to a selective sweep in
      African populations, the Trp64 variant possibly representing the selection
      target. Given the previous association of the ancestral ADRB3 Arg64 allele with
      obesity and type 2 diabetes, dietary adaptations might represent the underlying
      selective force.

PMID- 19576572
TI  - The delta(1) opioid receptor is a heterodimer that opposes the actions of the
      delta(2) receptor on alcohol intake.
AB  - BACKGROUND: Opioid receptors are clinically important targets for both pain and
      alcohol abuse. Three opioid receptors have been cloned: mu, delta, and kappa, all
      of which effect alcohol consumption in animal models. Naltrexone is a
      nonselective opioid antagonist used for alcoholism, the clinical utility of which
      is limited by poor efficacy and adverse side effects. Here, we demonstrate that
      the therapeutic limitations of naltrexone may reflect its poor selectivity.
      Despite decades of research, several mysteries surround the pharmacology of these
      receptors. For example, two pharmacologically defined subtypes of delta receptors
      exist in vivo. METHODS: Effects of delta subtype-selective ligands (naltrindole,
      naltriben, tan-67, 7-benzylidene naltrexone) were measured on ethanol consumption
      in C57BL/6 wildtype and opioid receptor knockout mice using a limited access two
      bottle choice paradigm. Affinity and efficacy of naltriben, 7
      benzylidenenaltrexone and tan-67 was measured in vitro using radioligand binding
      and Ca(2+)-mobilizationa assays. RESULTS: We show that the subtypes of the delta
      receptor, delta(1) and delta(2), have opposing effects on ethanol consumption. We
      find that these effects are synergistic; thereby suggesting that delta(1) and
      delta(2) receptors are distinct molecular targets. Indeed, we provide both in
      vitro as well as in vivo evidence that the delta(1) subtype is a micro-delta
      heterodimer and that the delta(2) subtype is most likely a delta homomer.
      CONCLUSIONS: Together these data provide insight into the limited actions of the
      clinically important drug naltrexone and identify a novel target with improved
      specificity and efficacy for the development of new therapeutics for the
      treatment of alcoholism.

PMID- 19576573
TI  - Ventro-striatal reductions underpin symptoms of hyperactivity and impulsivity in
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Models of attention-deficit/hyperactivity disorder (ADHD) classically
      emphasize the relevance of executive processes and, recently, reward circuits.
      The neural bases of reward processes have barely been explored in relation to
      this disorder, in contrast to extensive neuroimaging studies that examine
      executive functions in patients with ADHD. To our knowledge, no previous studies
      have analyzed the volume of the ventral striatum, a key region for reward
      processes in ADHD children. METHODS: We used a manual region-of-interest approach
      to examine whether there were volumetric differences in the ventral striatum of
      ADHD children. Forty-two children/adolescents with ADHD (ages 6-18), and 42
      healthy control subjects matched on age, gender, and handedness were selected for
      the study. RESULTS: The ADHD children presented significant reductions in both
      right and left ventro-striatal volumes (t = 3.290, p = .001; and t = 3.486, p =
      .001, respectively). In addition, we found that the volume of the right ventral
      striatum negatively correlated with maternal ratings of hyperactivity/impulsivity
      (r = -.503, p = .003). CONCLUSIONS: Our study provides neuroanatomical evidence
      of alterations in the ventral striatum of ADHD children. These findings coincide
      with previous explicative models as well as with recent reports in behavioral and
      functional neuroimaging studies. Furthermore, the negative correlations we
      observed strongly uphold the relation between the ventral striatum and symptoms
      of hyperactivity/impulsivity.

PMID- 19576576
TI  - Structure of an abequose-containing O-polysaccharide from Citrobacter freundii
      O22 strain PCM 1555.
AB  - The lipopolysaccharide of Citrobacter freundii O22 (strain PCM 1555) was degraded
      under mild acidic conditions and the O-polysaccharide released was isolated by
      gel chromatography. Sugar and methylation analyses along with (1)H and (13)C NMR
      spectroscopy, including two-dimensional (1)H,(1)H ROESY and (1)H,(13)C HMBC
      experiments, showed that the repeating unit of the O-polysaccharide has the
      following structure: alpha-Abep 1 -->3 --> 2)-alpha-D-Manp-(1-->4)-alpha-L-Rhap
      (1-->3)-alpha-D-Galp-(1--> where Abe is abequose (3,6-dideoxy-D-xylo-hexose). SDS
      PAGE and immunoblotting revealed that the O-antigen of C. freundii O22 is
      serologically indistinguishable from those of Salmonella group B serovars
      (Typhimurium, Brandenburg, Sandiego, Paratyphi B) but not related to other
      abequose-containing O-antigens tested (Citrobacter werkmanii O38 and Salmonella
      Kentucky) or colitose (l enantiomer of abequose)-containing O-antigen of
      Escherichia coli O111.

PMID- 19576575
TI  - Discrimination learning, reversal, and set-shifting in first-episode
      schizophrenia: stability over six years and specific associations with medication
      type and disorganization syndrome.
AB  - BACKGROUND: The intradimensional/extradimensional (IDED) task assesses different
      forms of learning from feedback. Limited evidence suggests that attentional set
      shifting deteriorates over time in schizophrenia. We tested this hypothesis and
      examined the specificity of learning impairments identified by this task. METHOD:
      Two hundred sixty-two first-episode patients and 76 healthy control subjects,
      matched for age and premorbid IQ, were tested; 104 patients and 25 control
      subjects were reassessed 1 and 3 years later, and 31 patients were reassessed
      additionally 6 years later. RESULTS: Patients showed impaired set-shifting that
      correlated with current IQ and working memory, but there were no impairments when
      subgroups were matched on current IQ. In contrast, patients showed marked
      impairments in rule reversal learning that survived correction for IQ, were
      present in the context of intact rule abstraction, and correlated with
      disorganization symptoms. Patients prescribed second-generation antipsychotics
      were worse on set-shifting compared with first-generation, a finding not
      explained by demographic data, illness characteristics, or IQ. Patients and
      control subjects showed stable IDED performance over the first 6 years of
      illness, although set-shifting was inconsistent over the first year. Those with
      residual negative symptoms were more likely to fail the set-shifting stage at
      follow-up. CONCLUSIONS: First-episode schizophrenia patients can learn and
      generalize rules but are inflexible when rules change, reflecting reduced
      responsiveness to negative feedback and difficulty in switching attention. Rule
      reversal is a promising target for translational studies, because it is specific,
      clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is
      related to poor function more generally but might be sensitive to medication
      effects and valuable for clinical trials.

PMID- 19576574
TI  - Alcohol consumption indices of genetic risk for alcohol dependence.
AB  - BACKGROUND: Previous research has reported a significant genetic correlation
      between heaviness of alcohol consumption and alcohol dependence (AD), but this
      association might be driven by the influence of AD on consumption rather than the
      reverse. We test the genetic overlap between AD symptoms and a heaviness of
      consumption measure among individuals who do not have AD. A high genetic
      correlation between these measures would suggest that a continuous measure of
      consumption may have a useful role in the discovery of genes contributing to
      dependence risk. METHODS: Factor analysis of five alcohol use measures was used
      to create a measure of heaviness of alcohol consumption. Quantitative genetic
      analyses of interview data from the 1989 Australian Twin Panel (n = 6257
      individuals; M = 29.9 years) assessed the genetic overlap between heaviness of
      consumption, DSM-IV AD symptoms, DSM-IV AD symptom clustering, and DSM-IV alcohol
      abuse. RESULTS: Genetic influences accounted for 30%-51% of the variance in the
      alcohol measures and genetic correlations were .90 or higher for all measures,
      with the correlation between consumption and dependence symptoms among
      nondependent individuals estimated at .97 (95% confidence interval: .80-1.00).
      CONCLUSIONS: Heaviness of consumption and AD symptoms have a high degree of
      genetic overlap even among nondependent individuals in the general population,
      implying that genetic influences on dependence risk in the general population are
      acting to a considerable degree through heaviness of use and that quantitative
      measures of consumption will likely have a useful role in the identification of
      genes contributing to AD.

PMID- 19576577
TI  - A lectin from the Chinese bird-hunting spider binds sialic acids.
AB  - The affinity to sialic acid-containing oligosaccharides of the small-animal
      lectin SHL-I isolated from the venom of the Chinese bird-hunting spider
      Selenocosmia huwena is here described for the first time. By a strategic
      combination of NMR techniques, molecular modeling, and data mining tools it was
      possible to identify the crucial amino acid residues that are responsible for SHL
      I's ability to bind sialic acid residues in a specific way. Furthermore, we are
      able to discuss the role of the functional groups of sialic acid when bound to
      SHL-I. Also the impact of Pro31 in its cis- or trans-form on SHL-I's ligand
      affinity is of special interest, since it answers the question if Trp32 is a
      crucial amino acid for stabilizing complexes between SHL-I and sialic acid. SHL-I
      can be considered as a proper model system that provides further insights into
      the binding mechanisms of small-animal lectins to sialic acid on a sub-molecular
      level.

PMID- 19576578
TI  - Unintended embodiment of concepts into percepts: sensory activation boosts
      attention for same-modality concepts in the attentional blink paradigm.
AB  - This study shows that sensory priming facilitates reports of same-modality
      concepts in an attentional blink paradigm. Participants had to detect and report
      two target words (T1 and T2) presented for 53 ms each among a series of nonwords
      distractors at a frequency of up to 19 items per second. SOA between target words
      was set to 53 ms or 213 ms, with reduced attention expected for T2 under the
      longer SOA (attentional blink) and for T1 under the shorter SOA (lag-1 sparing).
      These effects were found but reduced when the sensory modality of the concepts
      matched that of a sensory stimulation occurring prior to the detection trial.
      Hence, sensory activation increased report for same-modality concepts. This
      finding reveals that grounded cognition effects (1) are involved in conceptual
      processing as soon as a word has reached the point of lexical identification and
      (2) occur independent of intentional access to sensory properties of concepts.

PMID- 19576579
TI  - Categorical structure among shared features in networks of early-learned nouns.
AB  - The shared features that characterize the noun categories that young children
      learn first are a formative basis of the human category system. To investigate
      the potential categorical information contained in the features of early-learned
      nouns, we examine the graph-theoretic properties of noun-feature networks. The
      networks are built from the overlap of words normatively acquired by children
      prior to 2(1/2) years of age and perceptual and conceptual (functional) features
      acquired from adult feature generation norms. The resulting networks have small
      world structure, indicative of a high degree of feature overlap in local
      clusters. However, perceptual features--due to their abundance and redundancy-
      generate networks more robust to feature omissions, while conceptual features are
      more discriminating and, per feature, offer more categorical information than
      perceptual features. Using a network specific cluster identification algorithm
      (the clique percolation method) we also show that shared features among these
      early-learned nouns create higher-order groupings common to adult taxonomic
      designations. Again, perceptual and conceptual features play distinct roles among
      different categories, typically with perceptual features being more inclusive and
      conceptual features being more exclusive of category memberships. The results
      offer new and testable hypotheses about the role of shared features in human
      category knowledge.

PMID- 19576580
TI  - Re-evaluating split-fovea processing in word recognition: effects of fixation
      location within words.
AB  - It has been claimed that word recognition is affected fundamentally by the
      precise location at which a word is fixated because a precise split in
      hemispheric processing at the point of fixation causes all letters to the left
      and right of fixation to project to different, contralateral hemispheres. To
      assess this claim, 5-letter words (and nonwords) were presented for lexical
      decision when participants fixated the space immediately to the left (location 1)
      or right (location 6) of each stimulus, or one of the four possible inter-letter
      spaces (locations 2-5). Fixation location was controlled using an eye-tracker
      linked to a fixation-contingent display and all stimuli were presented entirely
      within foveal vision to avoid confounding influences of extrafoveal hemispheric
      projections. Performance was equally poorest when fixating locations 1 and 6
      (when words were shown entirely to either the right and left of fixation),
      intermediate for location 5, and equally superior for locations 2, 3, and 4.
      Additional word-specific analyses also showed no evidence of the effects of
      fixation location on optimal word recognition predicted by split-fovea
      processing. These findings suggest that, while fixation location influences word
      recognition, word recognition is apparently not affected by a split in
      hemispheric processing at the point of fixation and does not depend critically on
      the precise location at which a word is fixated. Implications of these findings
      for the role of fixation location in word recognition are discussed.

PMID- 19576581
TI  - Diagnosis of colorectal lesions with the magnifying narrow-band imaging system.
AB  - BACKGROUND: Narrow-band imaging (NBI) emphasizes the surface microvasculature of
      the GI tract and may help in detecting small neoplasms. OBJECTIVE: The aim of
      this study was to clarify the value of the NBI system in tissue characterization
      and differential diagnosis. DESIGN: A prospective study. SETTING: Digestive
      Disease Center of Showa University Northern Yokohama Hospital. PATIENTS: The
      subjects were 495 patients who, from January 2006 to June 2007, underwent a
      complete colonoscopic examination. A total of 617 lesions were evaluated in the
      495 patients (33 hyperplastic polyps, 532 adenomas, 52 submucosally invasive [T1]
      cancers). RESULTS: Most hyperplastic polyps showed a faint pattern. The vascular
      patterns of adenomas were mainly the network pattern or the dense pattern. The
      major vascular patterns of cancers were the irregular pattern and the sparse
      pattern. The irregular pattern was characteristic for protruded or flat-elevated
      cancers, whereas the sparse pattern was unique for depressed cancers. When we
      assumed that the faint pattern was diagnostic for hyperplastic polyps, we could
      differentiate between neoplastic and non-neoplastic lesions with a sensitivity of
      90.9% and a specificity of 97.1%. Likewise, irregular and sparse patterns were
      assumed to be indices of massively invasive submucosal cancer, the sensitivity
      was 100%, the specificity was 95.8%, and the accuracy rate was 96.1%.
      LIMITATIONS: This study was performed at a single center. CONCLUSIONS: The NBI
      system was valuable for distinguishing between neoplastic and non-neoplastic
      lesions, as well as between cancers and adenomas. Vascular pattern analysis can
      also be a promising tool for determining treatment selection, either endoscopy or
      surgery.

PMID- 19576582
TI  - H infinity decentralized observation and control of nonlinear interconnected
      systems.
AB  - In this paper, we investigate the problem of H(infinity) decentralized tracking
      control design with a decentralized observer for interconnected nonlinear systems
      which are characterized by the interconnection of N subsystems. Each subsystem is
      modeled by a linear constant part perturbed by an additive nonlinearity which is
      illustrated by the interconnection terms. The proposed feedback control scheme is
      developed to ensure the asymptotic stability of the augmented system, to
      reconstruct the non-measurable state variables of each subsystem, to maximize the
      nonlinearity domain, and to improve the performance of the model reference
      tracking control by using the H(infinity) criterion despite the external
      disturbances. The proposed control approach is formulated in a minimization
      problem and derived in terms of linear matrix inequalities (LMIs) whose
      resolution yields the decentralized control and observation gain matrices. The
      effectiveness of the proposed control scheme is demonstrated through numerical
      simulations on a power system with three interconnected machines.

PMID- 19576583
TI  - "Challenges in the management of fractures in osteopetrosis"! Review of
      literature and technical tips learned from long-term management of seven
      patients.
AB  - Osteopetrosis is a metabolic disorder with diminished bone resorption due to
      osteoclastic abnormality. It causes hard and brittle marble bone which fractures
      easily. Most of these fractures can be treated conservatively. Operative
      intervention when needed presents with unique technical challenges. While
      osteopetrotic hard bone may be penetrated with a drill bit; high friction and
      prolonged drilling can make the drill bit blunt. The heat generated can cause
      bone necrosis and break the drill bit. Besides this, brittleness of bones can
      cause intra-operative fractures. Due to the difficulties during the operation,
      the operative time may be prolonged thereby increasing the risk of post-operative
      infection. There is also a risk of delay in consolidation and non-union owning to
      impaired bone remodelling. We present an account of seven patients treated for
      various fracture related problems occurring throughout their life due to this
      disease. Difficulties encountered during their treatment prompted us to present
      some general management principles.

PMID- 19576584
TI  - Cervical prolapse during pregnancy and Klippel-Trenaunay syndrome.

PMID- 19576585
TI  - Angle of mediolateral episiotomy using the ischial tuberosity as a reference
      point.

PMID- 19576586
TI  - Active matrix metalloproteinases 3 and 9 are independently associated with
      coronary artery in-stent restenosis.
AB  - OBJECTIVE: This study aimed to determine whether plasma levels of active matrix
      metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New
      Zealand patients treated with bare-metal coronary stents. METHODS: A group of 152
      patients with a history of ISR were compared with 151 symptom free 1-year post
      stenting patients (non-ISR). Demographic and angiographic characteristics were
      collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and
      -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based
      isoform sensitive assays. RESULTS: Both active MMP-9 and active MMP-3 were
      independently associated with history of ISR. Elevated levels of both active MMP
      3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for
      association with ISR, with 37% of ISR patients having such levels versus 11% on
      non-ISR. The addition of both of the MMP biomarkers significantly increased the
      area under the curve (AUC) of a receiver operator characteristic (ROC) analysis
      incorporating the significant demographic and angiographic variables (AUC 0.85
      versus 0.78, p<0.005). CONCLUSION: Measures of plasma active MMP isoforms appear
      to be independently associated with ISR, and assessment of multiple MMP markers
      yields cumulative utility.

PMID- 19576587
TI  - Receptor for advanced glycation end products (RAGE) and its inflammatory ligand
      EN-RAGE in non-diabetic subjects with pre-mature coronary artery disease.
AB  - OBJECTIVE: Inflammation participates in atherosclerosis from its inception
      onwards. RAGE (receptor for advanced glycation end products) and its natural pro
      inflammatory ligand, EN-RAGE (extracellular newly identified RAGE-binding
      protein) have been implicated in various inflammatory diseases. In present study,
      we determined the expression of RAGE and EN-RAGE in peripheral blood mononuclear
      cells (PBMCs) of subjects with pre-mature coronary artery disease (CAD) for the
      first time. METHODS AND RESULTS: The study patients were angiographically proven
      non-diabetic patients with pre-mature CAD (Group I; N=100) and control group
      comprised of subjects with coronary risk factors and without coronary artery
      lesions (Group II; N=40). Semi-quantitative RT-PCR was performed to determine
      transcriptional expression of RAGE and EN-RAGE in PBMCs. Soluble RAGE (sRAGE) and
      C-reactive protein (hsCRP) levels were determined in serum of all study subjects
      using immunoassays. A significantly increased transcriptional expression of RAGE
      and EN-RAGE in PBMCs (p<0.01) of Group I patients was observed. Increased
      circulating hsCRP (p<0.01) levels and decreased sRAGE (p<0.01) levels were
      observed in Group I as compared with the Group II subjects. Severity of disease
      determined by Gensini score was found to be positively correlated with
      transcriptional expression of RAGE (r=0.530) and EN-RAGE (r=0.323). EN-RAGE
      expression revealed a strong association with RAGE (r=0.326), hsCRP (r=0.251) and
      a negative association with sRAGE (r=-0.222). CONCLUSIONS: Increased expression
      of RAGE and EN-RAGE in non-diabetic pre-mature CAD and various associations
      discussed may amplify several cellular perturbations and thus significantly
      contribute to the pathophysiology of CAD.

PMID- 19576588
TI  - Electroosmotic pump-assisted capillary electrophoresis of proteins.
AB  - A new method for protein analysis, that is, electroosmotic pump-assisted
      capillary electrophoresis (EOPACE), is developed and demonstrated to possess
      several advantages over other CE-based techniques. The column employed in EOPACE
      consists of two linked sections, poly(vinyl alcohol) (PVA)-coated and uncoated
      capillaries. The PVA-coated capillary column is the section for protein
      electrophoresis in EOPACE. Electroosmotic flow (EOF) is almost completely
      suppressed in this hydrophilic polymer coated section, so protein electrophoresis
      in the PVA-modified capillary is free of irreversible protein adsorption to the
      capillary inner wall. The uncoated capillary section serves as an electroosmotic
      pump, since EOF towards cathode occurs at neutral pH in the naked silica
      capillary. By the separation of a protein mixture containing cytochrome c (Cyt
      c), myoglobin and trypsin inhibitor, we have demonstrated the advantages of
      EOPACE method over other relevant ones such as pressure assisted CE, capillary
      zone electrophoresis (CZE) with naked capillary and CZE with PVA-coated
      capillary. A significant feature of EOPACE is that simultaneous separation of
      cationic, anionic and uncharged proteins at neutral pH can be readily
      accomplished by a single run, which is impossible or difficult to realize by the
      other CE-based methods. The high column efficiency and good reproducibility in
      protein analysis by EOPACE are verified and discussed. In addition, separation of
      tryptic digests of Cyt-c with the EOPACE system is demonstrated.

PMID- 19576589
TI  - Evaluation of various liquid chromatography-quadrupole-linear ion trap-mass
      spectrometry operation modes applied to the analysis of organic pollutants in
      wastewaters.
AB  - The LC-MS/MS analysis of a group of 14 organic pollutants in wastewater-
      including pharmaceuticals (analgesics/anti-inflammatories, lipid regulators and
      diuretics), pesticides (diuron) and disinfectants (chlorophene)--has been carried
      out using a hybrid triple quadrupole-linear ion trap-mass spectrometer (QqLIT).
      In order to take advantage of the capabilities of the QqLIT system, two methods
      have been developed and compared, based on the application of different operation
      modes. One of them uses selected reaction monitoring (SRM), which is the standard
      mode for quantitative LC-MS/MS analysis. The other is based on the use of an
      information dependent acquisition scan function (IDA), which allows the
      combination of a SRM acting as the survey scan and an enhanced product ion scan
      (EPI) as dependent scan within the same analysis. Performance of both methods was
      compared, especially in terms of their limits of detection and identification
      capability. The advantages and limitations of both techniques are discussed.
      Finally, the two methodologies developed were applied to real samples for
      evaluation of effluent wastewater in a treatment plant on the south-eastern
      Mediterranean coast of Spain. The presence of most of the target compounds was
      detected at mean concentrations ranging from 50 ng/L (mefenamic acid) to 3373
      ng/L (hydrochlorothiazide).

PMID- 19576590
TI  - Asymmetrical flow field-flow fractionation with multi-angle light scattering
      detection for the analysis of structured nanoparticles.
AB  - Synthesis and applications of new functional nanoparticles are topics of
      increasing interest in many fields of nanotechnology. Chemical modifications of
      inorganic nanoparticles are often necessary to improve their features as
      spectroscopic tracers or chemical sensors, and to increase water solubility and
      biocompatibility for applications in nano-biotechnology. Analysis and
      characterization of structured nanoparticles are then key steps for their
      synthesis optimization and final quality control. Many properties of structured
      nanoparticles are size-dependent. Particle size distribution analysis then
      provides fundamental analytical information. Asymmetrical flow field-flow
      fractionation (AF4) with multi-angle light scattering (MALS) detection is able to
      size-separate and to characterize nanosized analytes in dispersion. In this work
      we focus on the central role of AF4-MALS to analyze and characterize different
      types of structured nanoparticles that are finding increasing applications in
      nano-biotechnology and nanomedicine: polymer-coated gold nanoparticles,
      fluorescent silica nanoparticles, and quantum dots. AF4 not only size
      fractionated these nanoparticles and measured their hydrodynamic radius (r(h))
      distribution but it also separated them from the unbound, relatively low-M(r)
      components of the nanoparticle structures which were still present in the sample
      solution. On-line MALS detection on real-time gave the gyration radius (r(g))
      distribution of the fractionated nanoparticles. Additional information on
      nanoparticle morphology was then obtained from the r(h)/r(g) index. Stability of
      the nanoparticle dispersions was finally investigated. Aggregation of the
      fluorescent silica nanoparticles was found to depend on the concentration at
      which they were dispersed. Partial release of the polymeric coating from water
      soluble QDs was found when shear stress was induced by increasing flowrates
      during fractionation.

PMID- 19576592
TI  - Effects of glycols on the thermodynamic and micellar properties of TTAB in water.
AB  - Aggregation of tetradecyltrimethylammonium bromide, TTAB, in mixed solvent
      systems containing ethylene glycol, EG, 1,2-propylene glycol, 1,2-PROP, 1,3
      propylene glycol, 1,3-PROP, and tetraethylene glycol, TEG, has been investigated
      by employing conductivity and fluorescence methods. Gibbs energies of
      micellization were determined in order to evaluate the effects of the co-solvent
      on the aggregation process. Information about the influence of the organic
      solvent on the surfactant adsorption at the air-solution interface, on the
      micellar size and on the polarity of the micellar interfacial region was obtained
      by means of surface tension and fluorescence measurements. The study of the
      reaction methyl naphthalene-2-sulfonate + Br(-) in the water-glycol TTAB micellar
      solutions provided information about the characteristics of TTAB micelles as
      microreactors in the water-solvent binary mixtures.

PMID- 19576591
TI  - Multiresidue determination of 11 new fungicides in grapes and wines by liquid
      liquid extraction/clean-up and programmable temperature vaporization injection
      with analyte protectants/gas chromatography/ion trap mass spectrometry.
AB  - A gas chromatographic ion trap mass spectrometry (GC-ITMS) method was developed
      for the determination of 11 new generation fungicides (benalaxyl, benalaxyl-M,
      boscalid, cyazofamid, famoxadone, fenamidone, fluquinconazole, iprovalicarb,
      pyraclostrobin, trifloxystrobin and zoxamide) in grapes and wines. Samples were
      extracted with ethyl acetate:hexane (1:1, v/v) and cleaned-up with graphitized
      carbon black/primary secondary amine (GCB/PSA) solid-phase extraction (SPE)
      cartridges using acetonitrile:toluene (3:1, v/v) as eluent. The addition of
      analyte protectants (3-ethoxy-1,2-propanediol, d-sorbitol and l-gulonic acid
      gamma-lactone) in the final extracts allowed to avoid the matrix-induced response
      enhancement effect on quantitation process with absolute recoveries ca. 100%.
      Precision (expressed as relative standard deviation) was lower than 16% for all
      fungicides. Limits of detection and quantitation were lower than 0.01 mg/kg or
      mg/L, except for cyazofamid, much smaller in all cases than maximum residue
      levels (MRLs) established by European Union for grapes and by Switzerland and
      Italy for wines. The proposed method was applied to determine fungicide residues
      in three different white grapes for vinification produced in Ribeiro area in
      Galicia (NW Spain), as well as in their corresponding final wines.

PMID- 19576593
TI  - Impediments to the accurate structural characterisation of a highly concentrated
      emulsion studied using NMR diffusion diffraction.
AB  - Pulsed gradient spin-echo (PGSE) NMR diffusion studies with subsequent analysis
      using the Gaussian phase distribution (GPD) approach have long been used to
      determine the structure of emulsions. With the increasing availability of
      spectrometers equipped with higher gradient strength generation capabilities it
      is possible to extend PGSE measurements to where diffusive diffraction effects
      become evident. However the GPD approach cannot predict these diffraction-like
      coherence features which can be a rich source of information. With appropriate
      modelling based on the short gradient pulse approximation (SGP) such coherence
      features can provide morphological characteristics such as pore size, tortuosity,
      and connectivity. Further, the deviation of coherence features from ideal cases
      can be used to elucidate additional features such as the polydispersity of
      emulsion droplets which is a fundamental and crucial physical characteristic that
      influences the emulsion stability, rheology, and functionality. In this study
      analysis of PGSE NMR diffusion diffraction coherence features using the multiple
      propagator matrix formalism extension of the SGP approach is used to study
      structural characteristics of a highly concentrated emulsion.

PMID- 19576594
TI  - Amphiphile self-aggregation: an attempt to reconcile the agreement-disagreement
      between the enthalpies of micellization determined by the van't Hoff and
      Calorimetry methods.
AB  - In this article, discrepancies between the enthalpies of micellization of
      amphiphiles in aqueous solution determined by the methods of van't Hoff (VH) and
      calorimetry have been addressed. The contributions of the hydrophobic
      interaction, electrostatic interaction and the micellar size effect have been
      considered to assess the total picture of the amphiphile self-association process
      and related energetic parameters, especially the enthalpy and the specific heat
      capacity. Literature results on 23 amphiphile systems (six nonionics, five
      anionics, and twelve cationics) have been analyzed, and the assessed enthalpies
      by VH method and direct calorimetry have been presented and compared. VH results
      considering participation of 5% of total amphiphile monomer to form micelle at
      cmc have been also compared. In addition to this, the changes in the standard
      specific heat of micellization for all the amphiphile aggregation processes
      evaluated by the VH and calorimetry procedures have been presented. The
      differences between the standard enthalpy of micellization DeltaH(m)(o) by the
      methods of VH and calorimetry are minor for nonionic surfactants but major for
      ionics, whereas the standard specific heat capacities of micellization
      (DeltaC(Pm)(o)) by both the procedures fairly agree for all types of surfactants.
      Like DeltaH(m)(o)-DeltaS(m)(o) compensation observed in kinetic and equilibrium
      processes, a linear correlation between Lt(T-->0)DeltaH(m)(o) and DeltaC(Pm)(o)
      has been observed with no distinction between the VH and calorimetry derived
      results for all the surfactant systems herein dealt with.

PMID- 19576595
TI  - Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis
      for acute ischemic stroke.
AB  - BACKGROUND: The presence of a hyperdense middle cerebral artery sign (HMCAS) on
      baseline brain CT is associated with poor clinical outcome in stroke patients
      treated with intravenous recombinant tissue plasminogen activator (tPA). It
      remains uncertain whether the presence of HMCAS is associated with acute
      neurological deterioration after tPA treatment. OBJECTIVE: To evaluate the effect
      of HMCAS in routinely intravenous tPA-treated patients with anterior circulation
      stroke on acute neurological deterioration, the 3-month functional outcome and
      the occurrence of symptomatic ICH. METHODS: We analyzed data from a single stroke
      unit registry of 384 consecutive patients with anterior circulation infarction,
      treated with intravenous tPA. Logistic regression models were used to assess if
      HMCAS was independently associated with predefined outcome definitions. RESULTS:
      We found a HMCAS in 104 patients (27%). The HMCAS was related to the risk of
      early neurological deterioration (p=0.04) and poor functional outcome (p<0.001)
      on univariate analysis. The incidence of symptomatic ICH was not significantly
      different between patients with and without HMCAS (7% versus 6%, p=0.81). In the
      multivariable analysis, the presence of HMCAS was significantly associated with a
      poor outcome (p=0.004). CONCLUSIONS: The HMCAS is associated with early
      neurological deterioration and poor functional outcome, but not with symptomatic
      ICH.

PMID- 19576597
TI  - [Alcoholic patient with abdominal pain and vomits].

PMID- 19576598
TI  - [Drug-induced lupus].
AB  - Drug-induced lupus (DIL) is syndrome characterised by the occurrence of lupus
      like symptoms and serological findings, following exposure to certain drugs. A
      substantial number of drugs can induce the positivity of antinuclear antibodies
      (ANA) but the diagnosis of DIL cannot be done in the absence of clinical
      features. Most patients with DIL have constitutional symptoms, arthralgia or
      occasionally arthritis, myalgias, fever and weight loss. These features may take
      weeks or months to develop and use to be mild with renal and central nervous
      system happening very rarely. ANA are always positive. They are mainly anti
      histone proteins. Antibodies to ds-DNA are a rare finding and would tend to
      favour a diagnosis of idiopathic SLE. They have been associated with the use of
      tumour necrosis factor inhibitors (ant-TNF) and minocycline. Some drugs can
      induce particular symptoms o serological abnormalities and the diagnosis may be
      more difficult. It is the case of minocycline-induced lupus, which uses to affect
      young women with anti-ds-DNA and p-ANCA antibodies positive and negative anti
      histone antibodies. Treatment with anti-TNF alpha is frequently associated with
      the development of ANA and anti-DNA. The incidence of ANA positive varies between
      23-57% and anti-DNA between 9-33%. However, only a small number of patients will
      develop DIL or vasculitis. Resolution or marked improvement of the symptoms
      generally occurs within 2-5 weeks of the drugs withdrawal although some patients
      may require non-steroid anti-inflammatory drug or low dose steroid.
      Immunosuppressive drugs may be needed in severe cases with renal or neurological
      involvement. Some patients remain ANA positive for long periods of time. No
      treatment is necessary for ANA positive in the absence of clinical features.

PMID- 19576599
TI  - [De novo I172N mutation in a patient with 21-hydroxilase deficiency].

PMID- 19576596
TI  - Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA
      shunt enzymes.
AB  - Seleno-organic compound, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), is a
      substrate with radical-scavenging activity. In this study, we observed the
      neuroprotective effects of ebselen against ischemic damage and on GABA shunt
      enzymes such as glutamic acid decarboxylase 67 (GAD67), GABA transaminse (GABA-T)
      and succinic semialdehyde dehydrogenase (SSADH) in the hippocampal CA1 region
      after 5 min of transient forebrain ischemia in gerbils. For this, vehicle
      (physiological saline) or ebselen was administered 30 min before or after
      ischemia/reperfusion and sacrificed 4 days after ischemia/reperfusion. The
      administration of ebselen significantly reduced the neuronal death in the CA1
      region induced by ischemia/reperfusion. In addition, treatment with ebselen
      markedly elevated GAD67, GABA-T and SSADH immunoreactivity and their protein
      levels compared to that in the vehicle-treated group, respectively. These results
      suggest that ebselen protects neurons from ischemic damage via control of the
      expressions of GABA shunt enzymes to enter the TCA cycle.

PMID- 19576600
TI  - [Giant inguinal lymph node to secondary squamous cell carcinoma of penis].

PMID- 19576602
TI  - [Global prognosis in heart failure: pulmonary hypertension and comorbidity].

PMID- 19576603
TI  - [Kaposi's sarcoma of the stomach with concurrent HIV infection (epidemic form)].

PMID- 19576604
TI  - [Subconjunctival haemorrhage in a 5 year old child from Equatorial Guinea].

PMID- 19576605
TI  - [Update on the use of contrast agents in ultrasonography: a review of the
      clinical guidelines of the European Federation of Societies for Ultrasound in
      Medicine and Biology (EFSUMB)].
AB  - The aim of this article is to review the current indications for the use of
      contrast agents in ultrasonography in imaging departments with reference to the
      guidelines and recommendations recently published by the European Federation of
      Societies for Ultrasound in Medicine and Biology (EFSUMB). The article begins
      with a brief description of currently available contrast agents, of their adverse
      effects and contraindications, and of the specific techniques that enable the
      signal emitted from the microbubbles in the contrast to be detected. Next, we
      review the indications for ultrasound contrast agents both in the liver
      (detecting and characterizing focal lesions as well as guiding and monitoring
      percutaneous treatments) and outside the liver (in the kidney, vesicoureteral
      reflux, pancreas, traumatisms, and cerebral circulation). For each of the
      indications, first we describe the interpretation of the findings, then the
      recommended uses, and finally the limitations of the technique. Finally, we
      review all the other applications that have yet to be included in the EFSUMB
      guidelines.

PMID- 19576606
TI  - Comment on: GB virus infection: a silent anti-HIV panacea within?

PMID- 19576607
TI  - A feasibility study of temperature rise measurement in a tissue phantom as an
      alternative way for characterization of the therapeutic high intensity focused
      ultrasonic field.
AB  - The feasibility that temperature field measurements in vitro as an alternative
      way to characterize the high intensity focused ultrasound (HIFU) field used in
      therapeutic applications has been explored in a phantom study. Thermocouples
      (copper-constantan, diameter 0.125 mm) are embedded in a phantom filled with
      tissue mimicking material that simulates the thermal and acoustic properties of
      soft-tissue. The temperature rises as a function of ultrasound exposure time near
      the focus of a HIFU transducer (1.1 MHz, active radius a=32 mm, geometric focal
      length=62 mm) of various acoustic powers up to 30 W are measured and compared
      with predicted values using a simple nonlinear Gaussian model. The experimental
      results can be explained well by the model if no acoustic cavitation takes place.
      When the acoustic power become higher (>5 W) and the local temperature elevation
      >15 degrees C and the local temperature is >40 degrees C at the focal point,
      cavitation vapor bubbles appear. The presence of the cavitation bubbles may
      increase the temperature rise rate initially. The bubble aggregates may form
      along the beam axis under sonication and then eventually makes the temperature
      elevation reach a saturated value. When acoustic cavitation occurs, the bubble
      assisted enhancement of the initial temperature rise (exposure time t<2s) can
      still be predicted by the theory.

PMID- 19576608
TI  - Detection of Cryptosporidium spp. and Giardia duodenalis in surface water: a
      health risk for humans and animals.
AB  - The objective of the present study was to determine the degree of contamination
      by Cryptosporidium spp. and Giardia duodenalis in a river basin in a livestock
      farming area in Galicia (NW, Spain). Water samples (50 l) were collected at 22
      points in the main basin (including 5 recreational areas), and at the source and
      mouth of the 3 most important rivers and at the mouth of a smaller, secondary
      river. Faecal samples were collected from dairy cattle selected at random from 18
      herds farmed in the area. A total of 139 neonatal calves, 480 heifers and 697
      cows were sampled. The prevalence, intensity of infection and the risk associated
      with the spread of infection by both enteropathogens were determined. Water and
      faecal samples were collected in spring, summer, autumn and winter of 2007. The
      species and genotypes of these parasites present in the water samples were
      identified. In both water and faecal samples, more parasitic stages were
      collected in spring and summer than in autumn and winter. In spring,
      Cryptosporidium spp. oocysts were detected in 33 (9.4%) cows from 13 (72.2%)
      herds, and G. duodenalis cysts were detected in 56 (16.0%) cows from 15 farms
      (83.3%); the intensity of infection ranged from 5 to 7895 G. duodenalis cysts per
      gram of faeces. Infective stages of Cryptosporidium spp. and G. duodenalis were
      also detected in respectively 26 (89.6%) and 27 (93.1%) water samples, in spring.
      The mean concentrations of parasites ranged from 2 to 1200 Cryptosporidium spp.
      oocysts per litre and from 2 to 400 G. duodenalis cysts per litre.
      Cryptosporidium parvum, C. andersoni, C. hominis and assemblages A-I, A-II, E of
      G. duodenalis were detected. The presence of both protozoans must be monitored in
      cattle, in sources of water used for recreational purposes and in artificial
      waterways used by farmers (water channels, animal drinking water and drainage
      systems).

PMID- 19576609
TI  - Simultaneous removal of Cu, Mn and Zn from drinking water with the use of
      clinoptilolite and its Fe-modified form.
AB  - Zeolites have been widely used in water treatment and especially clinoptilolite,
      due to its low cost and high abundance. It has large cation-exchange capacity and
      is capable of removing large quantities of heavy metals from contaminated water
      samples. By loading the surface of clinoptilolite with amorphous Fe-oxide
      species, a total improvement in adsorption capacity could be achieved. Thus, the
      Clin-Fe oxide system is capable of adsorbing significantly higher heavy metal
      concentrations than untreated clinoptilolite with simultaneous noticeable
      decrease in water hardness. Batch adsorption experiments have shown that Clin-Fe
      system has very large Cu, Zn and Mn adsorption capacity and for most of the cases
      the treated water samples were suitable for human consumption or agricultural
      use. New experiments were conducted to study the effectiveness of clinoptilolite
      and of the Clin-Fe system in removal of Cu, Mn, Zn, present simultaneously in
      water samples, so that the study of metal-sorbent chemical behavior and of the
      adsorption selectivity would be feasible. Desorption of metals was also examined
      and an integrated approach of the effectiveness of such materials in drinking
      water treatment is presented.

PMID- 19576611
TI  - Simulated rain events on an urban roadway to understand the dynamics of mercury
      mobilization in stormwater runoff.
AB  - This research focuses on mercury (Hg) mobilization in stormwater runoff from an
      urban roadway. The objectives were to determine: how the transport of surface
      derived Hg changes during an event hydrograph; the influence of antecedent dry
      days on the runoff Hg load; the relationship between total suspended sediments
      (TSS) and Hg transport, and; the fate of new Hg input in rain and its relative
      importance to the runoff Hg load. Simulated rain events were used to control
      variables to elucidate transport processes and a Hg stable isotope was used to
      trace the fate of Hg inputs in rain. The results showed that Hg concentrations
      were highest at the beginning of the hydrograph and were predominantly
      particulate bound (HgP). On average, almost 50% of the total Hg load was
      transported during the first minutes of runoff, underscoring the importance of
      the initial runoff on load calculations. Hg accumulated on the road surface
      during dry periods resulting in the Hg runoff load increasing with antecedent dry
      days. The Hg concentrations in runoff were significantly correlated with TSS
      concentrations (mean r(2)=0.94+/-0.09). The results from the isotope experiments
      showed that the new Hg inputs quickly become associated with the surface
      particles and that the majority of Hg in runoff is derived from non-event surface
      derived sources.

PMID- 19576610
TI  - Inhibition of sulfate-reducing and methanogenic activities of anaerobic sewer
      biofilms by ferric iron dosing.
AB  - Ferric iron is commonly used for sulfide precipitation in sewers, thus achieving
      corrosion and odour control. Its impact on the activities of sulfate-reducing
      bacteria and methanogens in anaerobic sewer biofilms is investigated in this
      study. Two lab-scale rising main sewer systems fed with real sewage were operated
      for 8 months. One received Fe(3+) dosage (experimental system) and the other was
      used as a control. In addition to precipitating sulfide from bulk water, Fe(3+)
      dosage was found to significantly inhibit sulfate reduction and methane
      production by sewer biofilms. The experimental reactor discharged an effluent
      containing a higher concentration of sulfate and a lower concentration of methane
      in comparison with the reference reactor. Batch experiments showed that the
      addition of ferric ions reduced the sulfate reduction and methane production
      rates of the sewer biofilms by 60% and 80%, respectively. The batch experiments
      further showed that Fe(3+) dosage changed the final products of sulfate reduction
      with sulfide accounting for only 54% of the sulfate reduced. The other products
      could not be confirmed, but were not dissolved inorganic sulfur species such as
      sulfite or thiosulfate. The results suggest the addition of Fe(3+) at upstream
      locations would minimize the ferric salts required for achieving the same level
      of sulfide removal. Fe(3+) dosing could also substantially reduce the formation
      of methane, a potent greenhouse gas, in sewers.

PMID- 19576612
TI  - Enhancing the formation and shear resistance of nitrifying biofilms on membranes
      by surface modification.
AB  - Polypropylene (PP) membranes and polyethylene (PE) surfaces were modified to
      enhance formation and shear resistance of nitrifying biofilms for wastewater
      treatment applications. A combination of plasma polymerization and wet chemistry
      was employed to ultimately introduce poly(ethyleneglycol) (PEG) chains with two
      different functional groups (-PEG-NH(2) and -PEG-CH(3)). Biofilm growth
      experiments using a mixed nitrifying bacterial culture revealed that the specific
      combination of PEG chains with amino groups resulted in most biofilm formation on
      both PP and PE samples. Detachment experiments showed similar trends: biofilms on
      -PEG-NH(2) modified surfaces were much stronger compared to the other
      modifications and the unmodified reference surfaces. Electrostatic interactions
      between the protonated amino group and negatively charged bacteria as well as PEG
      chain density which can affect the surface structure might be possible
      explanations of the superiority of the -PEG-NH(2) modification. The success of
      the-PEG-NH(2) modification was independent of the original surface and might,
      therefore, be used in wastewater treatment bioreactors to improve reactor
      performance by making biofilm formation more stable and predictable.

PMID- 19576613
TI  - A hybridized photocatalysis-microfiltration system with iron oxide-coated
      membranes for the removal of natural organic matter in water treatment: effects
      of iron oxide layers and colloids.
AB  - A photocatalysis/microfiltration (MF) hybrid system, with the coating of a
      membrane using iron oxide particles (IOPs), was investigated with respect to
      natural organic matter (NOM) removal and membrane permeability during the
      treatment of various surface waters. A comparison of the performance between bare
      (uncoated) and IOP-coated membranes employed for the photocatalytic hybrid system
      was made. Due to the additional adsorption of NOM onto IOPs on the membrane
      surface, the IOP-coated membrane system always achieved greater DOC removal
      efficiencies during photocatalysis/MF. Particularly, the influence of colloidal
      particles that were present in different water sources with respect to membrane
      fouling was explored. Colloidal fouling occurred to both bare and IOP-coated
      membranes, but the interaction of colloids with IOP coating layers was in close
      association with the characteristics of colloids, such as size distribution,
      resulting in opposing fouling behaviors with varying water sources. The IOP
      coated membrane was able to control fouling properly when a relatively large size
      of colloidal particles existed in raw water, but not for the case of small
      colloids. The IOP coat layer may become denser as small colloids penetrate into
      it, therefore leading to further fouling. The analysis of the hydraulic
      filtration resistances revealed that such fouling was virtually reversible in
      being removed by backwashing processes. Scanning electron microscopic
      observations, however, visualized the existence of several foulants remaining at
      the membrane surface after backwashing when feed water, containing a relatively
      large portion of small-sized colloids, was supplied.

PMID- 19576614
TI  - Application of a molecular biology concept for the detection of DNA damage and
      repair during UV disinfection.
AB  - As nucleic acids are major targets in bacteria during standardised UV
      disinfection (254 nm), inactivation rates also depend on bacterial DNA repair.
      Due to UV-related DNA modifications, PCR-based approaches allow for a direct
      detection of DNA damage and repair during UV disinfection. By applying different
      primer sets, the correlation between amplicon length and PCR amplification became
      obvious. The longer the targeted DNA fragment was, the more UV-induced DNA
      lesions inhibited the PCR. Regeneration of Pseudomonas aeruginosa, Enterococcus
      faecium, and complex wastewater communities was recorded over a time period of 66
      h. While phases of intensive repair and proliferation were found for P.
      aeruginosa, no DNA repair was detected by qPCR in E. faecium. Cultivation
      experiments verified these results. Despite high UV mediated inactivation rates
      original wastewater bacteria seem to express an enhanced robustness against
      irradiation. Regeneration of dominant and proliferation of low-abundant, probably
      UV-resistant species contributed to a strong post-irradiation recovery
      accompanied by a selection for beta-Proteobacteria.

PMID- 19576615
TI  - Degradation of fipronil in anaerobic sediments and the effect on porewater
      concentrations.
AB  - The current study measured the degradation of fipronil in laboratory-spiked silt
      loam sediment under anaerobic conditions at different aging times. The half-life
      of fipronil in anaerobic sediments spiked at 5.8+/-0.049 and 21+/-1.4microg/kg
      dry weight (dw) was 21+/-0.22 and 15+/-0.11d, respectively. Fipronil-sulfide was
      the primary degradation product with fipronil-sulfone detected at lower
      concentrations. No degradation occurred to fipronil-sulfide and fipronil-sulfone
      over 200d in separate systems. A concurrent decline in sediment concentrations
      resulted in a decline of fipronil in sediment porewater with an increase in
      fipronil-sulfide and fipronil-sulfone measured by matrix-solid phase
      microextraction (matrix-SPME). Equilibrium among sediment, porewater, and matrix
      SPME fiber occurred within 138d for fipronil and fipronil-sulfone; however,
      fipronil-sulfide did not reach equilibrium during the test, and modeling
      predicted upwards of 1083d to reach equilibrium. Regardless of the time to reach
      equilibrium, the rapid degradation of fipronil has little ecological significance
      given that fipronil-sulfide and fipronil-sulfone have equal or greater toxicity,
      and exhibit greater environmental stability in both the sediment and porewater,
      thereby becoming bioavailable.

PMID- 19576617
TI  - Development of river biofilms on artificial substrates and their potential for
      biomonitoring water quality.
AB  - This study conducted several approaches to determine development and succession
      of different types of biofilms (i.e., colonization and accumulation biofilms).
      Changes in total metabolic activity, bacterial and algal composition within
      different biofilms from two river ecosystems were analyzed. They were related to
      water quality parameters in order to assess major factors influencing biofilm
      growth. Significant differences in chlorophyll a concentrations in biofilms and
      water between two rivers were due to differences in light intensity, water
      current velocity, and turbidity. Colonization of epilithic algae in biofilms
      mainly resulted from high levels of nutrients (up to 2.8 mgL(-1) of phosphate)
      and water chlorophyll a, and may be caused by attachment of planktonic algae.
      However, epilithic algae may also serve as the source of planktonic algae.
      Oxidizable substrates measured as chemical oxygen demand were found to directly
      increase bacterial growth or indirectly affect growth a week later. One-month
      colonization biofilms were the most sensitive to change of water quality, and had
      the greatest number of significant relationships to physico-chemical and
      biological parameters among three types of biofilms. This suggested that 1-month
      colonization biofilms were applicable for biomonitoring water quality.

PMID- 19576616
TI  - Global environmental cycling of gamma-HCH and DDT in the 1980s--a study using a
      coupled atmosphere and ocean general circulation model.
AB  - A coupled atmosphere-ocean general circulation model, ECHAM5-MPIOM, was used to
      study the multicompartmental cycling and long-range transport of persistent and
      semivolatile organics. Multiphase systems in air and ocean are covered by
      submodels for atmospheric aerosols, HAM, and marine biogeochemistry, HAMOCC5,
      respectively. The model, furthermore, encompasses 2D surface compartments, i.e.
      top soil, vegetation surfaces and sea-ice. The total environmental fate of gamma
      hexachlorocyclohexane (gamma-HCH, lindane) and dichlorophenyltrichloroethane
      (DDT) in agriculture were studied. DDT is mostly present in the soils, the water
      soluble gamma-HCH in soils and ocean. DDT has the longest residence time in
      almost all compartments. Quasi-steady state with regard to substance accumulation
      is reached within a few years in air and vegetation surfaces. In seawater the
      partitioning to suspended and sinking particles contributes to the vertical
      transport of substances. On the global scale deep water formation is, however,
      found to be more efficient. Up to 30% of DDT but only less than 0.2% of gamma-HCH
      in seawater are stored in particulate matter. On the time scale studied (1
      decade) and on global scale substance transport in the environment is determined
      by the fast atmospheric circulation. The meridional transport mechanism, for both
      compounds, is significantly enhanced by multi-hopping. Net meridional transport
      in the ocean is effective only regionally, mostly by currents along the western
      boundaries of Africa and the Americas. The total environmental burdens of the
      substances experience a net northward migration from their source regions, which
      is more pronounced for DDT than for gamma-HCH. Due to the application
      distribution, however, after 10 years of simulation 21% of the global
      environmental burden of gamma-HCH and 12% of DDT have accumulated in the Arctic.

PMID- 19576618
TI  - Can we use stable isotopes for ecotoxicological studies? Effect of DDT on
      isotopic fractionation in Perca fluviatilis.
AB  - Nitrogen and carbon stable isotope analyses are frequently used to assess
      contaminant biomagnification in animals in the wild. Previous studies, mainly on
      plant but also on animal tissues, have shown that chemical stress can lead to
      shifts in delta(15)N. In order to assess if an exposure to DDT at realistic
      concentration disrupted stable isotope signature in animals, delta(15)N and
      delta(13)C were studied in several tissues (liver, muscle, gill) of Perca
      fluviatilis fed with the same commercial diet uncontaminated or contaminated with
      DDT. We observed no DDT effect on the delta(15)N and delta(13)C of fish tissues.
      Our results show that stable isotopes can remain useful for field
      ecotoxicological studies despite food-chain contamination. However, correlations
      between the delta(13)C or delta(15)N values measured in the different organs were
      only found in DDT treated fish, suggesting some disruption of major biochemical
      compound metabolism in tissues.

PMID- 19576619
TI  - Taphonomy of the early Miocene flora, Hiwegi Formation, Rusinga Island, Kenya.
AB  - A fossil flora was collected in situ from early Miocene deposits at site R117 in
      the Hiwegi Formation of Rusinga Island contemporaneous with and in close
      proximity to the sites from where the anthropoid primates were recovered. The
      flora exhibits a spatially and temporally patchy distribution of fruits and
      seeds, mixed with twigs of various sizes, fragments of wood, bark, and leaves,
      all with random orientations and very low depositional dips. There has been
      minimal transport and the flora evidently accumulated as in situ litter beneath
      local vegetation. Based on Nearest Living Relatives (NLR) of fruits and seeds,
      the vegetation represented is a deciduous broad-leaved woodland with continuous
      canopy, with trees, shrubs, lianas, and climbers, reminiscent of the structure of
      the modern vegetation in the steep-sided protected valleys in the Laetoli-Endulen
      area. The interpretation of the vegetation is supported by the presence of twigs,
      wood, and bark fragments from larger diameter axes. Climbers are represented by
      twining stem fragments as well as by a wide variety of distinctive fruits and
      seeds. The proportion of fossilised thorny twigs represents only 3% of the twig
      collections, and there are no unequivocal forest trees amongst the NLR. No
      grasses were present; monocotyledons are only represented by a single date palm
      stone. No conifer seeds or cones have been recovered, and there are no coniferous
      leafy shoots.

PMID- 19576620
TI  - Mercury distribution and speciation in water and fish from abandoned Hg mines in
      Wanshan, Guizhou province, China.
AB  - Concentrations of total mercury (Hg(T)), methylmercury (MeHg), and its speciation
      in water samples as well as fish collected from abandoned Hg mines in Wanshan,
      Guizhou province, China, were measured to show regional dispersion of Hg
      contaminations that are not well known. High Hg(T) and MeHg(T) (total
      methylmercury) concentrations obtained in waters from mining areas, ranged from
      15 to 9300 ng/l and 0.31 to 25 ng/l, respectively. MeHg(T) were not correlated
      with Hg(T), whereas, peak values in both cases were in accord with high
      concentrations of particulate fraction, which appeared to be enhanced during high
      flow regime with ratios reaching to 99%. Elevated Hg concentrations in the
      particulate form indicated that particles released from Hg mining tailings
      (calcines) might be an important pathway of Hg to the aquatic system. The
      concentrations of total Hg in fish muscle were elevated ranging from 0.061 to
      0.68 mg/kg, but MeHg were generally low ranging from 0.024 to 0.098 mg/kg with a
      mean ratio of 28%. The concentrations and distribution patterns of Hg in aquatic
      systems suggested derivation from historic Hg mining sites in the Wanshan area.

PMID- 19576621
TI  - Isolated groin recurrence of vulvar cancer salvaged with multimodality therapy.

PMID- 19576622
TI  - Rapamycin by itself and additively in combination with carboplatin inhibits the
      growth of ovarian cancer cells.
AB  - OBJECTIVE: The current standard treatment for ovarian carcinoma, consisting of
      surgery followed by chemotherapy with carboplatin and paclitaxel, is fraught with
      a high rate of recurrences. We hypothesized that targeted inhibition of specific
      signaling pathways in combination with conventional drugs may increase
      chemotherapeutic efficacy. METHODS: We analyzed the expression and activation
      profiles of various signaling pathways in nine established ovarian cancer cell
      lines (CAOV-3, ES2, PA-1, SKOV-3, NIHOVCAR3, OV90, TOV112D, A1847, A2780) and 24
      freshly procured human ovarian tumors. The PI3 kinase pathway component Akt was
      frequently overexpressed and/or activated in tumor cells. The effect of several
      PI3K pathway inhibitors (rapamycin, LY294002, SH-6) and rapamycin in combination
      with carboplatin on various tumor cell growth characteristics was tested in cell
      lines and fresh tumor-derived transient monolayer and organ cultures. RESULTS:
      Rapamycin by itself and additively with carboplatin inhibited the growth and
      invasion, and increased the sensitivity to anoikis of most of the ovarian cancer
      cell lines and fresh tumors. The additive inhibitory effect may be due to
      enhanced apoptosis as demonstrated by Poly-ADP-Ribose Polymerase (PARP) cleavage
      and Annexin V staining in cells treated with both rapamycin and carboplatin.
      CONCLUSIONS: Rapamycin in combination with standard chemotherapeutic agents may
      improve the efficiency of ovarian cancer treatment.

PMID- 19576623
TI  - Prevention of tamoxifen induced endometrial polyps using a levonorgestrel
      releasing intrauterine system long-term follow-up of a randomised control trial.
AB  - OBJECTIVES: In a RCT, we have previously shown that the levonorgestrel
      intrauterine system (LNG-IUS, Mirena) produces a decidual response protecting the
      endometrium at one year follow-up. We here report on the long-term follow-up of
      this group of women, to test the hypothesis that a LNG-IUS could prevent the pro
      proliferative uterine responses of tamoxifen for up to 4.5 years. METHODS: A
      randomised-controlled trial of postmenopausal women who had taken at least one
      year of adjuvant tamoxifen therapy. RESULTS: One hundred twenty-two women were
      recruited. Nine were found to be ineligible after randomisation. The average
      duration of follow-up was 26.25 months (IQR 14.5-36 months) in the surveillance
      group and 24.2 months (IQR 13.75-32.5 months) in the LNG-IUS group. Women with
      LNG-IUS in situ at the time of final assessment had decidualised endometrium, and
      no polyps. In the surveillance group new polyps arose in 8 cases. There were 3
      new polyps in the group initially randomised to LNG-IUS, one in a patient who did
      not have the device inserted and 2 occurred in patients following the removal of
      the LNG-IUS. Univariate Cox proportional hazards regression models identified
      only endometrial thickness at trial entry as a statistically significant variable
      (HR 1.12, 95% CI 1.02 to 1.22, p=0.01) for the development of polyps. CONCLUSION:
      This study confirms that LNG-IUS induces benign endometrial changes and prevents
      endometrial polyps but only during its use in women taking tamoxifen. Endometrial
      thickness is a risk factor for the development of polyps.

PMID- 19576624
TI  - WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis.
AB  - Metastasis from lung adenocarcinoma can occur swiftly to multiple organs within
      months of diagnosis. The mechanisms that confer this rapid metastatic capacity to
      lung tumors are unknown. Activation of the canonical WNT/TCF pathway is
      identified here as a determinant of metastasis to brain and bone during lung
      adenocarcinoma progression. Gene expression signatures denoting WNT/TCF
      activation are associated with relapse to multiple organs in primary lung
      adenocarcinoma. Metastatic subpopulations isolated from independent lymph node
      derived lung adenocarcinoma cell lines harbor a hyperactive WNT/TCF pathway.
      Reduction of TCF activity in these cells attenuates their ability to form brain
      and bone metastases in mice, independently of effects on tumor growth in the
      lungs. The WNT/TCF target genes HOXB9 and LEF1 are identified as mediators of
      chemotactic invasion and colony outgrowth. Thus, a distinct WNT/TCF signaling
      program through LEF1 and HOXB9 enhances the competence of lung adenocarcinoma
      cells to colonize the bones and the brain. For a video summary of this article,
      see the PaperFlick file available with the online Supplemental Data.

PMID- 19576625
TI  - Changes in extracellular osmolality initiate sperm motility in freshwater teleost
      rosy barb Puntius conchonius.
AB  - The objective was to investigate the effects of extracellular osmolality and
      membrane osmotic-sensitive channels on the initiation of sperm motility and to
      explore mechanisms of sperm initiation in rosy barb (Puntius conchonius). We
      found that (1) sperm were immotile in seminal plasma and remained quiescent in
      electrolyte or nonelectrolyte solutions isotonic to seminal plasma; (2) sperm
      movement was initiated when the sperm were exposed to hypo-osmotic electrolyte or
      hypo-osmotic nonelectrolyte solutions, and that the responsiveness of sperm to
      changes in the extracellular osmolalities (100, 200, 250, 270, and 300 mOsm/kg)
      differed among sperm cells (P<0.05); (3) sperm movement could be initiated and
      terminated repeatedly by decreasing and increasing the osmolality (in increments
      of 100 and 300 mOsm/kg) of a nonelectrolyte mannitol solution, respectively
      (P<0.05); (4) gadolinium (20, 40, and 80 microM) inhibited the initiation of
      sperm motility and abolished the sperm activation caused by the hypo-osmotic
      media treatment in dose- and time-dependent manners (P<0.05); and (5) sperm
      activation in a hypo-osmotic medium and inhibition in an isotonic solution were
      associated with swelling and shrinkage of the sperm sleeves, respectively.
      Therefore, we concluded that osmolality was a critical physiologic signal in
      regulating the initiation and termination of sperm motility in freshwater teleost
      rosy barb. Furthermore, we inferred that rosy barb sperm were hypo-osmotic
      dependent conformers, and the osmotic-sensitive channel could be involved in the
      mechanism of sperm initiation.

PMID- 19576626
TI  - Is the early postnatal rise of testosterone responsible for a later male pattern
      of growth hormone secretion in pigs?
AB  - Sexual differentiation in Placentalia consists of several consecutive steps
      during fetal, postnatal, and premature development. It is known from male rats
      that an elevation in testosterone synthesis is observable within 2 d of birth,
      which leads to a male pattern of growth hormone (GH) secretion with low base
      levels and high amplitudes compared with that in females. In the male pig, a
      transient rise in testosterone concentration occurs about 4 wk after birth, but
      it is unknown whether it results in a later male pattern of GH secretion. In this
      study, male pigs (sus scrofa) were castrated either at 1 wk of age (Group 1, n=8)
      or at 6 wk of age (Group 2, n=8). Blood was sampled daily via cephalic vein
      catheters between 17 and 29 wk of age and analyzed for testosterone, GH, insulin
      like growth factor-1 (IGF-1), and urea. High-frequency blood sampling (every 20
      min over 24h) for determination of GH pulsatility was performed at ages 19 and 24
      wk. Total fat content and protein synthesis were determined at age 25 wk and at
      slaughter, respectively. Comparing Groups 1 and 2, there were no differences in
      daily GH concentrations or pulsatile secretion patterns, but in both groups, mean
      GH levels and pulsatility decreased from Week 19 to Week 24. Consequently, IGF-1,
      protein synthesis, urea, and body fat showed no differences when comparing both
      groups. It is concluded that the postnatal rise of testicular steroidogenesis in
      male pigs is not responsible for the later male pattern of GH secretion.

PMID- 19576627
TI  - Early perception of written syllables in French: An event-related potential
      study.
AB  - The present study examined whether written syllable units are perceived in first
      steps of letter string processing. An illusory conjunction experiment was
      conducted while event-related potentials were recorded. Colored pseudowords were
      presented such that there was a match or mismatch between the syllable boundaries
      and the color boundaries. The results showed that congruent stimuli for which the
      syllable and color boundaries coincided produced a greater positive-going
      waveform than incongruent stimuli for which the syllable and color boundaries did
      not coincide. This syllable-color congruency effect was observed to occur both
      prior to 100 ms, and in a time window commencing at 150 ms. This finding suggests
      that syllable units are perceived in the initial steps of French visual word
      processing. Moreover, this study underlines the specificity of the illusory
      conjunction paradigm as a relevant and powerful tool of investigation of
      sublexical units that are automatically evoked from word perception.

PMID- 19576628
TI  - A human mirror neuron system for language: Perspectives from signed languages of
      the deaf.
AB  - Language is proposed to have developed atop the human analog of the macaque
      mirror neuron system for action perception and production [Arbib M.A. 2005. From
      monkey-like action recognition to human language: An evolutionary framework for
      neurolinguistics (with commentaries and author's response). Behavioral and Brain
      Sciences, 28, 105-167; Arbib M.A. (2008). From grasp to language: Embodied
      concepts and the challenge of abstraction. Journal de Physiologie Paris 102, 4
      20]. Signed languages of the deaf are fully-expressive, natural human languages
      that are perceived visually and produced manually. We suggest that if a unitary
      mirror neuron system mediates the observation and production of both language and
      non-linguistic action, three prediction can be made: (1) damage to the human
      mirror neuron system should non-selectively disrupt both sign language and non
      linguistic action processing; (2) within the domain of sign language, a given
      mirror neuron locus should mediate both perception and production; and (3) the
      action-based tuning curves of individual mirror neurons should support the highly
      circumscribed set of motions that form the "vocabulary of action" for signed
      languages. In this review we evaluate data from the sign language and mirror
      neuron literatures and find that these predictions are only partially upheld.

PMID- 19576629
TI  - Lord Darzi: the reckoning.

PMID- 19576630
TI  - Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic
      crosslinking agents in corneal tissue engineering.
AB  - Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP=ring
      opening metathesis polymerization) of carbohydrate-functionalized norbornenes,
      are investigated as novel collagen crosslinking agents in corneal tissue
      engineering. The neoglycopolymers were incorporated into recombinant human
      collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan
      (GAG) mimics. The purely synthetic nature of these composites is designed to
      reduce susceptibility to immunological and allergic reactions, and to circumvent
      the transmission of animal infectious diseases. The collagen-neoglycopolymer
      biomaterials exhibit higher stability to collagenase-induced biodegradation than
      the control materials, composites of RHC III crosslinked using EDC/NHS (EDC=1
      ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS=N-hydroxysuccinimide). Even at
      this proof of concept stage, the thermal stability, enzymatic resistance, and
      permeability of the neoglycopolymer hydrogels are comparable or superior to those
      of these fully optimized control materials, which have successfully been tested
      clinically. Tensile strength is adequate for transplantation, but lower than that
      of the optimized control materials.

PMID- 19576631
TI  - Brain derived neurotrophic factor and neurotrophin-4 employ different
      intracellular pathways to modulate norepinephrine uptake and release in rat
      hypothalamus.
AB  - Classical actions of the neurotrophin family are related to cellular survival and
      differentiation. Moreover, acute effects of neurotrophins have been reported.
      Although neurotrophins effects on synaptic transmission at central nervous system
      level have been largely studied, acute effects of neurotrophins on hypothalamic
      noradrenergic transmission are still poorly understood. Thus, we have studied the
      effects of the neurotrophin family members nerve growth factor (NGF), brain
      derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) on norepinephrine
      (NE) neuronal uptake and its evoked release, as well as the receptor and the
      intracellular pathways involved in these processes in rat hypothalamus. Present
      results indicate that BDNF increased NE uptake and decreased its evoked release
      through a mechanism that involve Trk B receptor and phospholipase C. Moreover, NT
      4, also through the Trk B receptor, decreased NE uptake and its evoked release by
      activating phosphatidylinositol 3-OH-kinase. These effects were observed in whole
      hypothalamus as well as in the anterior hypothalamic zone. On the other hand, NGF
      did not modify noradrenergic transmission. In conclusion, we showed for the first
      time that BDNF and NT-4 activate two different intracellular signalling pathways
      through a Trk B receptor dependent mechanism. Furthermore, present findings
      support the hypothesis that BDNF and NT-4 acutely applied, could be considered as
      modulators of noradrenergic transmission and thus may regulate hypothalamic
      physiological as well as pathophysiological responses.

PMID- 19576632
TI  - Hazardous effect of tannery solid waste leachates on development and reproduction
      in Drosophila melanogaster: 70kDa heat shock protein as a marker of cellular
      damage.
AB  - Rapid industrialization has increased the burden of chemicals in the environment.
      These chemicals may be harmful to development and reproduction of any organism.
      We therefore analyzed the adverse effects of leachates from a tannery solid waste
      on development and reproduction using Drosophila. We show a significant delay in
      mean emergence of flies observed at the higher concentrations of the leachates,
      indicating their effect on the organism's development. Significant leachate
      induced effect on reproduction of the organism was also observed. Sub-organismal
      analyses revealed Hsp70 expression and tissue damage in a sex-specific manner.
      Refractoriness of Hsp70 expression in accessory glands of male flies and ovaries
      of females was concurrent with tissue damage. Genes encoding certain seminal
      proteins (Acp70A and Acp36DE) from accessory glands were significantly down
      regulated at higher concentrations of the leachates. The study suggests that (i)
      sub-organismal adverse responses are reflected at organismal level, (ii) tannery
      waste leachates cause adverse effects on the expression of genes encoding seminal
      proteins that facilitate normal reproduction and (iii) Hsp70 may be used as a
      marker of cellular damage for reproductive organs.

PMID- 19576633
TI  - Exposure to inhaled THM: comparison of continuous and event-specific exposure
      assessment for epidemiologic purposes.
AB  - Trihalomethanes (THMs) (chloroform, bromoform, dibromochloromethane, and
      bromodichloromethane) are the most abundant by-products of chlorination. People
      are exposed to THMs through ingestion, dermal contact and inhalation. The
      objective of this study was to compare two methods for assessing THM inhalation:
      a direct method with personal monitors assessing continuous exposure and an
      indirect one with microenvironmental sampling and collection of time-activity
      data during the main event exposures: bathing, showering and swimming. This
      comparison was conducted to help plan a future epidemiologic study of the effects
      of THMs on the upper airways of children. 30 children aged from 4 to 10 years
      were included. They wore a 3M 3520 organic vapor monitor for 7 days. We sampled
      air in their bathrooms (during baths or showers) and in the indoor swimming pools
      they visited and recorded their time-activity patterns. We used stainless steel
      tubes full of Tenax to collect air samples. All analyses were performed with Gas
      Chromatography and Mass Spectrometry (GC-MS). Chloroform was the THM with the
      highest concentrations in the air of both bathrooms and indoor swimming pools.
      Its continuous and event exposure measurements were significantly correlated
      (r(s)=0.69 p<0.001). Continuous exposures were higher than event exposures,
      suggesting that the event exposure method does not take into account some
      influential microenvironments. In an epidemiologic study, this might lead to
      random exposure misclassification, thus underestimation of the risk, and reduced
      statistical power. The continuous exposure method was difficult to implement
      because of its poor acceptability and the fragility of the personal monitors.
      These two points may also reduce the statistical power of an epidemiologic study.
      It would be useful to test the advantages and disadvantages of a second sample in
      the home or of modeling the baseline concentration of THM in the home to improve
      the event exposure method.

PMID- 19576634
TI  - Altered cutaneous expression of beta-defensins in dogs with atopic dermatitis.
AB  - Canine atopic dermatitis (AD) is a chronic allergic skin disorder with an
      immunopathogenesis comparable to that in humans with AD. The high frequency of
      recurrent infections with Staphylococcus pseudo intermedius and Malassezia
      pachydermatis may indicate a defective innate immune response in the skin of
      atopic dogs. Production of beta-defensins constitutes an important role in skin
      defense but information on canine beta-defensin localization and regulation is
      scarce. We conducted a gene-expression study of 16 canine beta-defensins (cBDs)
      in 11 tissues of healthy dogs, which revealed a variable expression of cBDs in
      different organ systems of the dog. In skin, three beta-defensins, cBD1, cBD103
      and cBD107, were extensively expressed, while inconsistent expression of five
      other beta-defensins was detected. Using immunohistochemistry abundant expression
      of cBD103 peptide was detected in the epidermis, hair follicles and sebaceous
      glands, comparable to hBD3 expression in human skin. To examine the gene
      expression of beta-defensins in atopic dogs, full thickness skin biopsy specimens
      (non-lesional and lesional) of 10 atopic dogs and 7 healthy dogs were examined
      with real-time PCR. A significant 12-fold increased expression of cBD1 was
      detected in lesional atopic skin compared to healthy skin, while non-lesional
      skin showed a 5-fold increase. Contrary to cBD1, expression of cBD103 was
      slightly (2-fold) downregulated in skin of atopic dogs. Gene-expression levels of
      S100A8, a marker for atopic dermatitis, were also highly upregulated in skin of
      atopic dogs, confirming the diagnostics of the skin biopsies. Taken together
      these results provide new evidence for a possible defect in the innate immune
      response of dogs with atopic dermatitis, and indicate the potential of the dog as
      a model for human AD.

PMID- 19576635
TI  - Transcription factor GATA-3 in Atlantic salmon (Salmo salar): molecular
      characterization, promoter activity and expression analysis.
AB  - GATA-3 is a T cell-specific transcription factor and is essential for the
      development of the T cell lineage and differentiation of T helper type 2 cells.
      We have identified and characterized the full-length Atlantic salmon GATA-3 cDNA
      (3074bp), having two zinc finger domains which are fully conserved within
      teleosts and higher vertebrates. RT-PCR analysis revealed that the Atlantic
      salmon GATA-3 (AsGATA-3) is strongly expressed in gills, thymus, and brain.
      Moreover, the involvement of GATA-3 in Atlantic salmon immune response was
      demonstrated by investigating the early time dependent expression profile of GATA
      3 in spleen and head kidney following intraperitoneal injection of live Aeromonas
      salmonicida, LPS, and beta-glucan. Furthermore, we have determined 1.9kb of
      upstream promoter sequence and found a number of sequence motifs which match
      those of known transcription factor binding sites and the AsGATA-3 promoter is a
      TATA-less promoter. Activities of presumptive regulatory regions of this gene
      were assessed by transfecting different 5' deletion constructs and the result
      showed the basal promoter and positive transcriptional regulator activity of
      AsGATA-3 gene is determined by sequences located between +58 and -199bp upstream
      of the transcriptional start site (TSS). This study provides further insights
      into the transcriptional regulation of AsGATA-3.

PMID- 19576637
TI  - Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype
      19A among children in Barcelona.
AB  - OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease (IPD)
      caused by Streptococcus pneumoniae serotype 19A. METHODS: We studied all children
      and adolescents with IPD caused by serotype 19A who were admitted to a Children's
      Hospital in Barcelona (1997-2007). Serotyping, antibiotic susceptibility and
      clonal analysis were performed. RESULTS: Comparing the pre-vaccine period (1997
      2001) with the early vaccine period (2002-2004) and the late vaccine period (2005
      2007) there was an increase of IPD caused by serotype 19A: 1 of 58 episodes
      (1.7%) vs. 8 of 54 episodes (14.8%) vs. 27 of 123 episodes (21.9%), respectively
      (P = 0.002). All S. pneumoniae serotype 19A isolated in the pre-vaccine and early
      vaccine periods (n = 9) were penicillin susceptible, while in the late vaccine
      period, 12 of 27 (44%) were penicillin nonsusceptible (P = 0.01). A clonal
      analysis revealed 15 different sequence types (STs) expressing serotype 19A. 10
      of them were preexisting STs associated with serotype 19A including the multidrug
      resistant ST320 and ST276. CONCLUSION: There was an increase of IPD caused by S.
      pneumoniae serotype 19A which was mainly related with the emergence of
      preexisting clones several of them closely related with international multidrug
      resistant clones. These results should be considered when selecting the new
      conjugate pneumococcal vaccines.

PMID- 19576636
TI  - Porin of Shigella dysenteriae directly promotes toll-like receptor 2-mediated
      CD4+ T cell survival and effector function.
AB  - Porin of Shigella dysenteriae type 1 up-regulated Toll-like receptor (TLR)2 on
      CD3-stimulated CD4(+) T cells but could not induce the expression of other TLRs.
      TLR2 in association with myeloid differentiating factor 88 (MyD88) triggered the
      downstream signal transduction pathway leading to activation of mitogen-activated
      protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB), and degradation of
      IkappaB, the NF-kappaB inhibitor. TLR2 co-stimulation by porin resulted in T cell
      expansion by inducing both proliferation and survival of the CD4(+) T cells.
      Extracellular signal-regulated kinase (ERK)1/2 activation inhibitor U0126 and NF
      kappaB translocation inhibitor SN-50 significantly inhibited proliferation of T
      cells, highlighting a direct role of ERK and NF-kappaB in the process. However,
      cell survival involving Bcl-X(L) induction was found to be regulated essentially
      by ERK with no significant role of NF-kappaB. Porin-induced proliferation was
      supported by induction of IL-2 and CD25 that are known to play a pivotal role in
      T cell expansion. Apart from inducing T cell proliferation, porin triggered
      effector functions of the cells, evident from TLR2- and MyD88-dependent release
      of type 1 cytokines tumor necrosis factor (TNF) and interferon (IFN)-gamma along
      with the induction of type 1 chemokines macrophage-inflammatory protein (MIP)
      1alpha and MIP-1beta and their receptor CCR5. The proliferation, survival and
      effector function of CD4(+) T cells through TLR2 co-stimulation show the
      capability of porin to directly turn adaptive immunity into action.

PMID- 19576639
TI  - A clinicopathological study of pulmonary mucormycosis in cancer patients:
      extensive angioinvasion but limited inflammatory response.
AB  - OBJECTIVES: Pulmonary mucormycosis (PMM) is an emerging, frequently lethal fungal
      infection in immunosuppressed cancer patients. We sought to characterize the
      histopathologic features of PMM in this population. METHODS: We identified
      patients with PMM who underwent autopsy or lung biopsy between 1990 and 2007.
      Histopathology slides were blindly reviewed by a pathologist and findings were
      scored on standardized forms. Pathologic findings were correlated with
      demographic and clinical data abstracted from patient's medical records. RESULTS:
      Twenty patients with PMM were included in this study. Nineteen patients (95%) had
      hematologic malignancies. High frequencies of angioinvasion (100%), hemorrhagic
      infarction (90%), coagulative necrosis (85%), and intra-alveolar hemorrhage (85%)
      were observed, whereas inflammatory infiltrates were uncommon (30%). Neutropenic
      patients had more extensive angioinvasion compared with non-neutropenic patients
      (77% versus 29%, P=0.06). Allogeneic hematopoietic stem cell transplantation
      (HSCT) recipients, all of whom had graft-versus-host disease, had more
      inflammatory cell infiltration but less intra-alveolar hemorrhage than non-HSCT
      patients (67% versus 14%, P=0.04; 50% versus 100%, P=0.02, respectively).
      CONCLUSIONS: PMM in immunocompromised cancer patients is characterized by
      extensive angioinvasion and coagulative necrosis. The different histopathologic
      features of PMM in neutropenic, non-neutropnic, and HSCT patients may reflect
      differences in the pathobiology of PMM in these populations.

PMID- 19576638
TI  - Molecular characterization of invasive serogroup Y Neisseria meningitidis strains
      isolated in the Latin America region.
AB  - OBJECTIVES: To improve the understanding of serogroup Y invasive meningococcal
      disease (IMD) in Latin America, particularly IMD molecular epidemiology; 166 Y
      serogroup isolates received at the National Reference Laboratories of Argentina,
      Brazil, Chile, Colombia, and Costa Rica during 2000-2006 were characterized by
      their molecular markers. METHODS: This analysis included serological assays to
      determine serogroup/serotype/serosubtype, DNA sequencing and genotyping of the
      porB and/or porA genes, multilocus sequence typing (MLST) and fetA allele
      determination. RESULTS: Sixteen different antigenic combinations were observed.
      Sixty-two (37.3%) isolates were NT:P1.5 and 36 (21.7%) isolates were 14:NST.
      Thirty-two different STs appeared, but 3 STs (ST-1624, ST-23, and ST-5770)
      accounted for 69.9% (116) of the strains. Most of the IMD isolates belonged to
      the ST-23, ST-167 clonal complexes or the group composed by ST-5770 and related
      STs. CONCLUSIONS: Isolates obtained in Colombia and Costa Rica were similar to
      that of the United States, in that most sequence types belonged to the ST-23
      clonal complex. IMD isolates found in Argentina appear to be the result of an
      independent event and did not spread from nearby countries, being the sequence
      type ST-1624 (ST-167 clonal complex) the most frequently found. We were unable to
      correlate an antigenic shift of outer membrane proteins with an increase of
      serogroup Y meningococcal cases in our collection of isolates.

PMID- 19576640
TI  - Evaluation of the NucliSens EasyQ HIV-1 v1.1 and RealTime HIV-1 kits for
      quantitation of HIV-1 RNA in plasma.
AB  - Human immunodeficiency virus type-1 (HIV-1) RNA viral load is an important
      biomarker to evaluate the therapeutic efficacy of antiretroviral drugs and to
      monitor disease progression in HIV-infected individuals. We compared HIV-1 RNA
      quantitation between two different kits, the NucliSens EasyQ HIV-1 v1.1 (EasyQ,
      bioMerieux) and RealTime HIV-1 (RealTime, Abbott), using HIV-1 RNA quality
      control (QC) materials, cell-cultivated viruses, and the plasma samples of 104
      patients with HIV. Correlation between the two kits for HIV RNA-1 quantitation
      with clinical samples was high (R=0.91). Based on results obtained with quality
      control standards, the reproducibility of the RealTime kit was higher than the
      EasyQ kit: the viral load value and coefficient of variation of each kit was
      4.11+/-0.136 and 3.3% for EasyQ and 3.55+/-0.042 and 1.2% for RealTime,
      respectively (P<0.002). This is the first comparative analysis of the detection
      limit and reproducibility of two different quantitation kits using clinical
      plasma samples from Korean HIV-1-infected patients. It will serve a useful
      reference to determine correction values for each HIV-1 RNA quantitation kits and
      to choose an appropriate assay kit for each laboratory.

PMID- 19576641
TI  - Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38
      pathway activation in PMA-induced macrophages.
AB  - BACKGROUND: Overproduction of MMPs (matrix metalloproteinases) and EMMPRIN
      (extracellular matrix metalloproteinase inducer) by monocytes/macrophages leads
      to atherosclerotic plaque rupture by degrading the extracellular matrix. Serum
      MMP-9 levels may therefore represent a novel marker of inflammation in patients
      with known coronary artery disease. The purpose of our study was to determine if
      berberine, a natural extract from Rhizoma coptidis, had any effect on the
      expression of MMP-9 and EMMPRIN in PMA-induced macrophages. METHODS: Human
      monocytic THP-1 cells were pretreated with berberine for 1 h, and then induced by
      PMA for 48 h. Total RNA and protein were collected for Real-time PCR and Western
      blot analysis, respectively. Culture supernatants were collected to determine MMP
      9 activity. RESULTS: In the present study, we demonstrated that berberine
      inhibited the expression of MMP-9 and EMMPRIN at both the mRNA and protein levels
      in a dose-dependent manner in PMA-induced macrophages, and that it also reduced
      MMP-9 activity. Furthermore, berberine also suppressed p38 signaling pathway
      activation in PMA-induced macrophages. CONCLUSIONS: The data indicate that
      berberine reduces MMP-9 and EMMPRIN expression by suppressing the activation of
      p38 pathway in PMA-induced macrophages. This suggests a potential role for
      berberine as a therapeutic aid for stabilizing atherosclerotic plaque.

PMID- 19576642
TI  - Endothelial progenitor cell capture stents--hype or hope?
AB  - The first report of late stent thrombosis leading to acute myocardial infarction
      in patients receiving the new CD34 antibody coated endothelial progenitor cell
      (EPC) capture stent may cast doubts on this technology. In our letter we review
      the potential risks and benefits of these stent types and give a short overview
      of recent alternative stent coatings for in vivo self endothelialization by using
      peptides, magnetic molecules or aptamers. Drawbacks with EPC capture stents
      should not lead to condemning this strategy in general, but rather stimulate
      research efforts to develop more suited capture molecules and more sophisticated
      coatings for the post-DES era towards more biological coatings which mimicry
      progenitor cell homing factors for rapid vascular wall regeneration.

PMID- 19576644
TI  - Copy-number variation: the end of the human genome?
AB  - Copy-number variation (CNV)--the presence of additional or missing segments of
      chromosomes in some individuals--has been found to be abundant in humans and adds
      another dimension of variation to the genome. Copy-number variants have already
      been associated with some diseases and disease susceptibilities and are likely to
      prove as significant as sequence polymorphisms in this respect. Changes in copy
      number of parts of the genome are known to be a feature of many cancers, and
      their analysis is expected to reveal genes involved in carcinogenesis. This
      article will present a somewhat biased and occasionally speculative discussion of
      the current and future significance of CNV with a particular focus on the
      potential of molecular copy-number counting in the analysis of small, damaged or
      heterogeneous samples.

PMID- 19576643
TI  - Bayesian analysis of a mastitis control plan to investigate the influence of
      veterinary prior beliefs on clinical interpretation.
AB  - The fundamental objective for health research is to determine whether changes
      should be made to clinical decisions. Decisions made by veterinary surgeons in
      the light of new research evidence are known to be influenced by their prior
      beliefs, especially their initial opinions about the plausibility of possible
      results. In this paper, clinical trial results for a bovine mastitis control plan
      were evaluated within a Bayesian context, to incorporate a community of prior
      distributions that represented a spectrum of clinical prior beliefs. The aim was
      to quantify the effect of veterinary surgeons' initial viewpoints on the
      interpretation of the trial results. A Bayesian analysis was conducted using
      Markov chain Monte Carlo procedures. Stochastic models included a financial cost
      attributed to a change in clinical mastitis following implementation of the
      control plan. Prior distributions were incorporated that covered a realistic
      range of possible clinical viewpoints, including scepticism, enthusiasm and
      uncertainty. Posterior distributions revealed important differences in the
      financial gain that clinicians with different starting viewpoints would
      anticipate from the mastitis control plan, given the actual research results. For
      example, a severe skeptic would ascribe a probability of 0.50 for a return of < 5
      UK pounds per cow in an average herd that implemented the plan, whereas an
      enthusiast would ascribe this probability for a return of > 20 UK pounds per cow.
      Simulations using increased trial sizes indicated that if the original study was
      four times as large, an initial skeptic would be more convinced about the
      efficacy of the control plan but would still anticipate less financial return
      than an initial enthusiast would anticipate after the original study. In
      conclusion, it is possible to estimate how clinicians' prior beliefs influence
      their interpretation of research evidence. Further research on the extent to
      which different interpretations of evidence result in changes to clinical
      practice would be worthwhile.

PMID- 19576645
TI  - Can we optimize chemo-radiation and surgery in locally advanced stage III non
      small cell lung cancer based on evidence from randomized clinical trials? A
      hypothesis-generating study.
AB  - PURPOSE: Improved local tumor control (LC) improves survival of patients with non
      small cell lung cancer (NSCLC). We estimated the capability of surgical and non
      surgical options to improve LC further in this disease. METHODS: Eligible studies
      were phase III trials reporting 2-year survival data as well as the incidence of
      LC and/or distant metastases. Effect estimates, as well as the statistical
      uncertainty of these, were combined in order to estimate the benefit in terms of
      LC from combining multiple modalities. RESULTS: It was estimated that the highest
      rates of LC can be obtained with high-dose concurrent chemo-radiation followed by
      surgery. In this situation, escalating the pre-operative radiation dose from 45
      to 66 Gy, delivered concurrently with chemotherapy, could increase LC from 58% to
      76%. Toxicity may also be higher, but could not be estimated. Without surgery,
      the gain in LC from concurrent chemo-radiation versus sequential, corresponds to
      a radiation dose increase from 65 to 72 Gy. CONCLUSIONS: We hypothesize that high
      dose concurrent chemo-radiation followed by surgery could be superior to other
      current treatment approaches for selected patients with stage III NSCLC, provided
      toxicity would be low. At present, high-dose concurrent chemo-radiation followed
      by surgery should be considered experimental.

PMID- 19576646
TI  - Effect of selective inhibitors of inflammation on oral mucositis: preclinical
      studies.
AB  - OBJECTIVE: Oral mucositis is a severe, dose-limiting side effect of
      radio(chemo)therapy for head and neck tumors. The epithelial radiation response
      (ulceration) is accompanied by inflammatory changes. Their interaction with the
      epithelial processes remains unclear. The present study was initiated to
      determine the effect of inhibition of TNF-alpha or COX-2 on the epithelial
      radiation response in the mouse tongue model. METHODS: Daily fractionated
      irradiation was given with 5 x 3 Gy/week over one (days 0-4) or two weeks (days 0
      4, 7-11). Each protocol was terminated by graded test doses (5 dose groups, 10
      animals each) to a defined area of the lower tongue surface to generate full dose
      effect curves for mucosal ulceration. A TNF-alpha inhibiting antibody
      (Infliximab) or a COX-2 inhibitor (Celecoxib) was administered. RESULTS: No
      effect of Infliximab or Celecoxib was found in any of the protocols. Isoeffective
      doses for ulcer induction were unchanged. Also, the time course of the response
      was largely unaffected. CONCLUSIONS: Inhibition of TNF-alpha or COX-2, two
      dominating inflammatory pathways, did not result in modulation of the response of
      oral epithelium during fractionated irradiation. This suggests that the
      inflammatory changes mediated through TNF-alpha or COX-2 are not relevant for the
      epithelial radiation response of oral mucosa.

PMID- 19576647
TI  - Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia
      formation in mouse kidneys.
AB  - BACKGROUND AND PURPOSE: Endoglin is a transforming growth factor beta (TGF-beta)
      co-receptor mainly expressed in dividing endothelial cells. It regulates cell
      proliferation and survival and is upregulated at sites of vessel repair.
      Mutations in endoglin have been linked to the vascular disease hereditary
      hemorrhagic telangiectasia (HHT). HHT patients display dilated capillaries
      (telangiectasia) that are prone to rupture. Cancer patients receiving
      radiotherapy develop similar vascular damage in normal tissues lying in the
      irradiation field. If located in the mucosa, irradiation-induced telangiectasia
      can lead to severe bleeding. Therefore, this study was aimed at investigating the
      role of endoglin in radiation-induced telangiectasia formation. MATERIALS AND
      METHODS: Kidneys of endoglin heterozygous (Eng(+/-)) or wild type mice were
      irradiated with 16 Gy. Mice were sacrificed after 20 weeks and changes in gene
      expression and protein levels were analysed. RESULTS: Expression of TGF-beta
      target genes involved in radiation-induced fibrosis and fibrosis development in
      the kidney decreased in Eng(+/-) compared to wild type mice. Unexpectedly, Eng(+/
      ) mice also displayed reduced telangiectasia formation in the irradiated kidney.
      CONCLUSIONS: Endoglin plays an important role in the development of irradiation
      induced normal tissue damage. Future studies will show whether interfering with
      endoglin functions protects tissues from late radiation toxicity.

PMID- 19576648
TI  - Ewing's sarcoma family tumors of the humerus: outcome of patients treated with
      radiotherapy, surgery or surgery and adjuvant radiotherapy.
AB  - BACKGROUND AND PURPOSE: Local treatment for non-metastatic Ewing's sarcoma family
      tumors (ESFTs) is controversial. Results achieved in a single institution in
      patients with ESFT of the humerus are presented. MATERIALS AND METHODS: Patients
      treated between 1983 and 2000 for ESFT of the humerus were included. The impact
      of local treatment (surgery, radiotherapy or both) on outcome was assessed.
      RESULTS: 55 patients: 34 males (62%); 21 females (38%); mean age: 17.9 (range: 3
      40). Local treatment: surgery in 27 patients (49%), radiotherapy in 17 (31%) and
      surgery followed by radiotherapy in 11 (20%). After a mean follow-up of 15 years
      (range: 7-25 years), 27 patients (49%) remained continuously disease free, 27
      (49%) relapsed and one died of chemotherapy toxicity. The local recurrence rate
      was 13% overall: 18% (3/17) after radiotherapy, 7% (2/27) after surgery and 19%
      (2/11) after surgery followed by adjuvant radiotherapy (p=ns). On the contrary,
      the 10-year EFS resulted significantly higher after surgery (64%) than
      radiotherapy (18%, p<0.01). The 10-year EFS after surgery followed by
      radiotherapy was 45%, non-significantly different from EFS of surgery or
      radiotherapy alone. The 3 treatment groups had a similar distribution of the most
      important prognostic variables for ESFT, except for the tumor-bone ratio, which
      was higher for patients who underwent radiotherapy, and surgical margins, more
      frequently inadequate in patients treated with a combination of radiotherapy and
      surgery compared to those managed by surgery alone. CONCLUSIONS: In conclusion
      this study shows that in EFST of the humerus surgery is the best treatment for
      small tumors. Large tumors are probably best treated with surgery too, as long as
      good functional results and quality of life can be expected, and adequate
      surgical margins are achievable. Postoperative radiotherapy is mandatory when
      margins are inadequate. A high local control rate, of more than 80%, can be
      obtained also by means of radiotherapy alone.

PMID- 19576649
TI  - Is heat shock protein 60 associated with type 2 diabetes mellitus?
AB  - AIMS: HSP60 plays a protective role against heat, oxidative injury and
      ultraviolet. Recently, animal and clinical studies have suggested that HSP60
      plays a role in various diseases. However, few epidemiological studies have
      demonstrated an association between HSP60 levels and type 2 diabetes mellitus.
      Therefore, an epidemiological study was conducted to examine the association of
      HSP60 with type 2 diabetes mellitus. METHODS: This study included 83 type 2
      diabetes mellitus patients and 161 controls that were recruited from male
      employees who received annual health check-ups between 2005 and 2007. The serum
      HSP60 levels were measured using the ELISA method. RESULTS: Because the HSP60
      levels were not detectable (<3.125 ng/mL) in 48.0% of the study subjects, HSP60
      levels were divided into two categories (detectable or undetectable). A logistic
      regression analysis showed that the subjects in the undetectable had a 2.03 times
      higher risk of diabetes mellitus than those in the detectable after adjustment
      for age, BMI and rate of hypertension medication. CONCLUSIONS: This study was the
      first epidemiological study to demonstrate an association between type 2 diabetes
      mellitus and HSP60, thus suggesting that HSP60 may play an important role in the
      type 2 diabetes mellitus pathology.

PMID- 19576650
TI  - Implementing evidence based guidelines: unlocking the secrets.

PMID- 19576651
TI  - Modeling the cost-effectiveness of different oral antiviral therapies in patients
      with chronic hepatitis B.
AB  - BACKGROUND/AIMS: Chronic hepatitis B (CHB) is a common disease associated with
      high morbidity, mortality and impact on healthcare costs. Several oral antiviral
      therapies can lead to complete virologic response, which is associated with
      prevention of disease progression. The aim of this study was to estimate the cost
      effectiveness of the oral antiviral treatments lamivudine, adefovir, telbivudine,
      entecavir and tenofovir, in patients with CHB. METHODS: A Markov model was used
      to project the lifetime complications and costs in cohorts of both HBeAg-positive
      and HBeAg-negative CHB patients treated with one of the above drugs or no
      treatment. Rescue therapy with two different combination therapies (adefovir plus
      lamivudine or tenofovir plus entecavir) with their corresponding costs and
      efficacy rates was also considered. The probabilities of disease progression were
      based on serum HBV DNA levels. Disease and complication costs were assessed using
      the perspective of the Spanish National Health System. RESULTS: The highest rate
      of virologic response was obtained with tenofovir, and this translated to its
      higher life years saved (LYS) and quality adjusted life years (QALY) compared
      with the rest of the alternatives in HBeAg-positive and HBeAg-negative patients.
      Tenofovir is associated with lower costs and higher efficacy over entecavir,
      telbivudine and adefovir in HBeAg-positive patients, and telbivudine and
      entecavir in HBeAg-negative patients. The incremental cost-effectiveness ratios
      with respect to the rest of the alternatives are below the common reference
      efficiency threshold of 30,000 euro per LYS/QALY. CONCLUSION: In chronic HBV
      infected patients, tenofovir is a cost-effective or even cost-saving strategy
      compared with other available treatment options for CHB.

PMID- 19576652
TI  - Complications of right lobe living donor liver transplantation.
AB  - BACKGROUND/AIMS: Right lobar living donor liver transplantation (LDLT) has been
      controversial because of donor deaths and widely variable reports of recipient
      and donor morbidity. Our aims were to ensure full disclosure to donors and
      recipients of the risks and benefits of this procedure in a large University
      center and to help explain reporting inconsistencies. METHODS: The Clavien 5-tier
      grading system was applied retrospectively in 121 consecutive adult right lobe
      recipients and their donors. The incidence was determined of potentially (Grade
      III), actually (Grade IV), or ultimately fatal (Grade V) complications during the
      first post-transplant year. When patients had more than one complication, only
      the seminal one was counted, or the most serious one if complications occurred
      contemporaneously. RESULTS: One year recipient/graft survival was 91%/84%. Within
      the year, 80 (66%) of the 121 recipients had Grade III (n=54) Grade IV (n=16), or
      Grade V (n=10) complications. The complications involved the graft's biliary
      tract (42% incidence), graft vasculature (15%), or non-graft locations (9%).
      Complications during the first year did not decline with increased team
      experience, and adversely affected survival out to 5 years. All 121 donors
      survive. However, 13 donors (10.7%) had Grade III (n=9) or IV (n=4) complications
      of which five were graft-related. CONCLUSIONS: Despite the satisfactory recipient
      and graft survival at our and selected other institutions, and although we have
      not had a donor mortality to date, the role of right lobar LDLT is not clear
      because of the recipient morbidity and risk to the donors.

PMID- 19576653
TI  - EASL clinical practice guidelines.

PMID- 19576655
TI  - Metastatic potential of lung squamous cell carcinoma associated with HSPC300
      through its interaction with WAVE2.
AB  - The small protein, HSPC300 (haematopoietic stem/progenitor cell protein 300), is
      associated with reorganization of actin filaments and cell movement, but its
      activity has not been reported in human cancer cells. Here, we investigated the
      association of HSPC300 expression with clinical features of lung squamous cell
      carcinoma. High levels of HSPC300 protein were detected in 84.1% of tumour
      samples, and in 30.8% of adjacent morphologically normal tissues. The number of
      primary tumours with elevated HSPC300 levels was significantly higher in primary
      tumours with lymph node metastases as opposed to those without, and also in
      tumours from patients with more advanced disease. HSPC300 modulates the
      morphology and motility of cells, as siRNA knockdown caused the reorganization of
      actin filaments, decreased the formation of pseudopodia, and inhibited the
      migration of a lung cancer cell line. We further showed that HSPC300 interacted
      with the WAVE2 protein, and HSPC300 silencing resulted in the degradation of
      WAVE2 in vitro. HSPC300 and WAVE2 were co-expressed in approximately 85.7% of
      primary tumours with lymph node metastases. We hypothesize that HSPC300 is
      associated with metastatic potential of lung squamous cell carcinoma through its
      interaction with WAVE2.

PMID- 19576657
TI  - Splicing in the eukaryotic ancestor: form, function and dysfunction.
AB  - Comparative genomics has begun to unravel the evolutionary history of transcript
      splicing in eukaryotes. The last common ancestor of modern eukaryotes is now
      known to have had at least moderately intron-dense genes and two complex
      spliceosomes. For other splicing-related phenomena the evolutionary history is
      less clear. We suggest that frequent mis-splicing is likely to be ancestral to
      eukaryotes, whereas trans-splicing and operon splicing are likely to be more
      recent. The origins of regulated splicing, alternative splicing and splicing of
      untranslated transcript regions are less certain. The data discussed underscore
      the significant genomic complexity of early eukaryotes, and should help to frame
      future questions about the origins of eukaryotic genome structure.

PMID- 19576656
TI  - Age at diagnosis predicts outcomes in gefitinib-treated female patients with non
      small-cell lung cancer.
AB  - We performed this retrospective study to evaluate the association between age at
      diagnosis and outcome in female patients with non-small-cell lung cancer, who
      were treated with gefitinib. We analyzed the outcomes for 162 female patients who
      had received gefitinib monotherapy. Receiver operating characteristic curve
      analysis was performed to select a cutoff value for age with respect to tumor
      response. Patients were categorized as older and younger, with a value of 55
      years. Most of the study population comprised never-smokers (89%) and patients
      with adenocarcinoma (82%). The mean age was 58 years and the response rate was
      47% (76 patients). Older female patients showed higher response rates than
      younger patients (57% and 27%, respectively; P<0.001), whereas there were no
      differences between never-smokers and smokers (P=0.824). Patients with
      adenocarcinoma had better response rates than those with nonadenocarinoma but
      this difference was not significant (50% and 34%, respectively; P=0.139). In
      terms of progression-free survival, older age (P=0.005) and adenocarcinoma
      histology (P=0.008) were favorable factors but never-smoking was not (P=0.316).
      Multivariate analysis confirmed that age predicted progression-free survival
      (hazard ratio, 0.60; P=0.008) and overall survival (hazard ratio, 0.60; P=0.014).
      Our data indicate that age at diagnosis may predict outcomes after gefitinib
      treatment in female patients with non-small-cell lung cancer. When molecular
      tests are not feasible, our results might help physician to select a beneficial
      subgroup in female patients.

PMID- 19576658
TI  - Cell-permeable ceramides act as novel regulators of U937 cell-cell adhesion
      mediated by CD29, CD98, and CD147.
AB  - Ceramides are signaling molecules that regulate differentiation, proliferation,
      and apoptosis of cells. In this study, we report novel modulatory effects of
      ceramides on the functional activation of beta1 integrins (CD29) and their
      associated molecules, such as CD98 and CD147, using U937 cell-cell or cell
      fibronectin (FN) adhesion events. Cell-permeable ceramides (C2- or C6-ceramides)
      effectively blocked monocytic cell-cell adhesion, mediated by CD29, CD98, and
      CD147, and cell-FN adhesion in a dose-dependent manner. The suppressive effect
      was demonstrated with the treatment of only ceramides but not other sphingolipid
      metabolites or analogs, such as sphingosine, dihydrosphingosine, and fumonisin
      B1. Ceramides displayed a distinct inhibitory profile on cell-cell and cell-FN
      adhesions compared with other inhibitors such as PD98059 (an extracellular signal
      related kinase (ERK) inhibitor), SB203580 (a p38 inhibitor), rottlerin (a
      PKCdelta inhibitor), and cytochalasin B (an actin cytoskeleton disruptor).
      Interestingly, C6-ceramide inhibited the phosphorylation of CD29 induced by
      MEM101A treatment and down-regulated surface levels of CD29, CD98, and CD147, as
      well as CD49d. Since there are no reports showing that ceramides act as negative
      regulators of the functional activation of CD29, our results therefore suggest a
      novel possibility that ceramides can be used as a therapeutic drug regarding CD29
      mediated pathological events, including tumor metastasis, inflammatory states,
      granuloma formation, and blood vessel occlusion.

PMID- 19576659
TI  - Abscisic acid regulates root hydraulic conductance via aquaporin expression
      modulation in Nicotiana tabacum.
AB  - Abscisic acid (ABA) modifies the hydraulic properties of roots by increasing root
      water flux. The effects of ABA on aquaporin content and root hydraulic
      conductance are controversial. We addressed these effects via a combination of
      experiments. Tobacco (Nicotiana tabacum) plants were grown hydroponically, and
      ABA (1 microM) was exogenously applied to the roots. Then, the water transport
      properties of tobacco roots and expression of PIP-type aquaporins were examined.
      ABA increased the sap flow rate (Jv) and also the osmotic root hydraulic
      conductance (Lp(r-o)) of excised tobacco roots after 24h. The expression of three
      aquaporin PIP-type genes and PIP1s proteins abundance in tobacco roots were
      analyzed by real-time PCR and protein gel blot analysis, respectively.
      Interestingly, the accumulation of NtAQP1, NtPIP1;1 and NtPIP2;1 transcripts and
      NtPIP1;1 and NtAQP1 proteins abundance was significantly increased. Although the
      antibody used recognize NtPIP1;1 and NtAQP1, most probably it also recognizes
      other PIP1 proteins present in tobacco. Thus, the increase in the expression of
      the three PIP-type genes and other PIP1s proteins abundance caused by ABA were
      correlated with an increase in Lp(r-o) and Jv. ABA therefore facilitated the cell
      to-cell component of water transport across the root cylinder. The subcellular
      localization of NtPIP1;1- and NtPIP2;1-GFP was investigated by protoplast
      transformation with chimeric gene, showing NtPIP2;1 localization in plasma
      membrane and NtPIP1;1 retention in the endoplasmic reticulum (ER). However, ABA
      did not change subcellular localization of NtPIP1;1 from ER to plasma membrane.

PMID- 19576660
TI  - The endogenous level of GA(1) is upregulated by high temperature during stem
      elongation in lettuce through LsGA3ox1 expression.
AB  - Bolting of lettuce is promoted by high temperatures. Gibberellins (GAs) play an
      important role in the bolting of several plant species, and it has been reported
      that exogenous GAs induce bolting and early flowering in lettuce. To clarify the
      role of GAs in this process, we examined the expression of genes involved in GA
      metabolism (LsGA20ox-1 and -2, LsGA3ox-1 and -2, and LsGA2ox-1 and -2) and
      endogenous GAs in lettuce stems. Quantitative reverse-transcription PCR indicated
      that the expression of a GA 3-oxidase gene, LsGA3ox1, is significantly
      upregulated by high (35/25 degrees C) temperature compared to low (25/15 degrees
      C) temperature, whereas transcription of the GA 20-oxidase gene, which is
      upregulated in long-day conditions in arabidopsis and spinach during bolting, is
      not clearly affected. Quantification of GA by liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS) showed that high temperature also
      upregulates the content of GA(1), a bioactive GA in lettuce. Our results suggest
      that LsGA3ox1 is a candidate for the gene responsible for the increase in GA(1)
      during lettuce bolting at high temperatures.

PMID- 19576661
TI  - Health care workers' perceptions of respiratory and gastrointestinal algorithms
      for patient management in emergency care settings.
AB  - BACKGROUND: Patients with respiratory or gastrointestinal illness in emergency
      care settings are often not yet diagnosed but are at risk of transmitting
      disease. Infection control algorithms delineating a standard approach to patient
      management decrease risk of secondary exposure, but few articles document health
      care workers' (HCWs) perceptions as to their effectiveness and ease of
      implementation. METHODS: A cross-sectional survey approach was used to explore
      HCWs perceptions in 2 emergency departments of the current algorithms for
      management of potentially infectious respiratory and gastrointestinal illnesses.
      RESULTS: Surveys from 96 HCWs revealed that algorithms were perceived as
      invaluable in protecting staff, patients, and colleagues. Differences in self
      reported compliance, clarity, and ease of implementation of the respiratory
      algorithm were noted between facilities, likely reflecting variation in the
      physical plant. Physicians scored significantly lower for compliance with the
      respiratory algorithm. CONCLUSION: Algorithms were perceived to offer a clear and
      consistent approach to patient management and protect HCWs in spite of
      environmental and resource limitations.

PMID- 19576663
TI  - Italian nursing students' perception of their clinical learning environment as
      measured with the CLEI tool.
AB  - CONTEXT: The quality of clinical learning environment is an important factor for
      nursing students' clinical experience and it is determined above all by a good
      atmosphere in the ward. The Clinical Environment Inventory (CLEI) has been
      developed to evaluate clinical learning environments. The CLEI has been found to
      be homogeneous and its validity has been established in several countries
      (Australia, England and China). METHODS: An exploratory study about Italian
      nursing students' perceptions of their learning environment was carried out using
      Chan's Clinical Learning Environment Inventory. The CLEI was translated into
      Italian and administered to 232 students from three levels of the nursing program
      in Trento hospital. The tool was administered after they finished the clinical
      placements. RESULTS: All of the questionnaires distributed were returned
      completed. The students overall perceived their clinical learning environment as
      good. Third year's students were extremely satisfied (94%) with activities done
      on the ward, while second year's students reported less satisfaction (88%). All
      the students (99%) agreed that practical work experience was useful and not a
      waste of time. CONCLUSIONS: This study shows that Italian nursing students have a
      positive perception of the clinical learning environment, although there remains
      room for improvement.

PMID- 19576662
TI  - Clinical features and molecular epidemiology of multidrug-resistant Acinetobacter
      calcoaceticus-A baumannii complex in a regional teaching hospital in Taiwan.
AB  - We conducted a case-controlled study in a regional teaching hospital in Taiwan to
      investigate the clinical features and molecular epidemiology of multidrug
      resistant Acinetobacter calcoaceticus-A baumannii (MDR Acb) complex. Case
      patients had higher mortality than controls did. MDR Acb complex acquisition risk
      factors include longer hospital stays, higher ratio of nasogastric tube and Foley
      catheter use, and more carbapenem use. All available isolates were divided into
      36 subtypes by pulsed-field gel electrophoresis. The proportion of the same
      subtypes with their appearance within 1 and 2 months was 62.5% and 87.5%,
      respectively. We concluded that many different MDR Acb complex clones could be
      found in a hospital and that the same clones often spread on a small scale within
      a short period of time if no outbreaks noted.

PMID- 19576664
TI  - Relationships between cardiovascular risk profile, ultrasonographic measurement
      of intra-abdominal adipose tissue, and waist circumference in obese children.
AB  - BACKGROUND & AIMS: Ultrasonographic measurements have been proposed to assess
      intra-abdominal adipose tissue. The aim of this study was to compare the
      relationship between waist circumference (WC), ultrasonographic measurements of
      intra-abdominal adipose tissue (UMA), and cardiovascular risk factors (CRF).
      METHODS: We determined blood pressure (BP), fasting HDL-cholesterol, LDL
      cholesterol, triglycerides, glucose, insulin resistance index HOMA, 2 h glucose
      in oral glucose tolerance test (oGTT), weight status (SDS-BMI), WC, and UMA in 89
      obese children. Furthermore, we analyzed the changes of CRF, SDS-BMI, WC, and UMA
      in 29 obese children participating in a one-year lifestyle intervention. RESULTS:
      In stepwise multivariable regression analysis, waist circumference was
      significantly associated to LDL-cholesterol, triglycerides, HOMA, and systolic
      blood pressure (adjusted variance (AV) 0.05-0.17). SDS-BMI was significantly
      related to triglycerides, HDL-cholesterol, 2 h glucose in oGTT, and diastolic
      blood pressure (AV 0.12-0.15), while UMA was related significantly to HOMA (AV
      0.04). The obese children participating in a lifestyle intervention significantly
      reduced their overweight, which was associated with a significant improvement of
      most CRF and a reduction of WC and UMA. Changes of WC were significantly
      correlated to changes of HDL-cholesterol (r=-0.45), HOMA (r=0.37), glucose
      tolerance (r=0.59), systolic BP (r=0.60), and diastolic BP (r=0.43), while change
      of SDS-BMI and UMA were not significantly related to any CRF. CONCLUSIONS:
      Compared to UMA, WC was stronger related to CRF in obese children. Therefore, the
      simple measurement of WC seems preferable as an indirect marker of CRF.

PMID- 19576665
TI  - Immune interference after sequential alphavirus vaccine vaccinations.
AB  - We compared the effect of order of administration of investigational alphavirus
      vaccines on neutralizing antibody response. Volunteers who received the
      inactivated eastern and western equine encephalitis (EEE and WEE) vaccines before
      live attenuated Venezuelan (VEE) vaccine had significantly lower rates of
      antibody response than those receiving VEE vaccine before EEE and WEE vaccines
      (66.7% vs. 80.6%; p=0.026). The odds of having a VEE antibody non-response among
      those initially receiving EEE and WEE vaccines, adjusted for gender, were
      significant (odds ratio [OR]=2.20; 95% CI=1.2-4.1 [p=0.0145]) as were the odds of
      non-response among females adjusted for group (OR=1.81; 95% CI=1.2-2.7
      [p=0.0037]). Antibody interference and gender effect have major implications for
      vaccine strategy among those receiving multiple alphavirus vaccines and those
      developing next generation vaccines for these threats.

PMID- 19576666
TI  - Clinical relevance of thymidylate synthase (TS) activity for S-1-based
      chemotherapy in squamous cell carcinoma of the oral cavity.
AB  - S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used
      as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma
      (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA
      biosynthetic pathway, and improves clinical response to chemotherapy with
      fluoropyrimidines. We have retrospectively evaluated the predictive value of
      thymidylate synthase activity in 75 patients with oral SCC with an enzyme-linked
      immunosorbent assay (ELISA). Mean (SD) activity (pmol/mg) in the specimens was
      0.078 (0.080) (median 0.059). The median value was taken as the cut-off value
      based on which the patients were divided into high and low activity groups. Both
      the clinical and histopathological responses to chemotherapy and
      radiochemotherapy were higher in the group with low TS activity. The group with
      low TS activity also differed significantly in their clinical response to S-1
      based chemotherapy (p<0.05). However, there was no significant difference in
      cause-specific survival. Measurement of TS activity may aid in predicting the
      clinical response to chemotherapy including S-1 for oral SCC.

PMID- 19576667
TI  - Problems with dental implants that were placed on vertically distracted fibular
      free flaps after resection: a report of six cases.
AB  - We report the clinical outcome of dental implants placed on vertically distracted
      fibular free flaps that were used to reconstruct maxillary and mandibular defects
      after resection. Distraction osteogenesis (DO) of fibular free flaps was used for
      six patients (5 men, 1 woman) a mean of 19 months (range 11-38) after 5
      mandibular and 1 maxillary reconstructions. A mean of 5 months (range 2-11) after
      removal of the distractor, 35 implants were inserted and loaded with implant
      supported fixed prostheses. The mean (range) follow-up period was 39 (17-81)
      months. The course of the DO and the clinical and radiographic outcomes of the
      implants were assessed. Of six vertically distracted fibular free flaps, there
      was one case of vector lingual tipping during the consolidation phase and a
      fracture of the basal fibular cortex that necessitated additional grafting with
      iliac bone to stabilise the distracted area. The mean (range) vertical bone gain
      was 14 (12-15) mm. Four of 35 implants (11%) failed during the follow-up period.
      The mean peri-implant bone resorption was 2.5mm. Cumulative implant survival was
      31/35 (89%) and survival after loading 31/33 (94%). Distraction osteogenesis of
      fibular free flaps caused a remarkable number of complications and pronounced
      resorption of bone around the implants, probably as a result of the formation of
      granulomatous tissue; a careful peri-implant follow-up and the maintenance of
      oral hygiene are essential.

PMID- 19576668
TI  - Continuous CO(2) capture and MSWI fly ash stabilization, utilizing novel dynamic
      equipment.
AB  - Novel dynamic equipment with gas in and out continuously was developed to study
      the capture capacity of CO(2). Municipal solid waste incineration (MSWI) fly ash
      has a high capture rate of CO(2) in CO(2)-rich gas. Fly ash can sequester pure
      CO(2) rapidly, and its capacity is 16.3 g CO(2)/100 g fly ash with no water added
      and 21.4 g CO(2)/100 g fly ash with 20% water added. For simulated incineration
      gas containing 12% CO(2), the capture rate decreased and the capacity was 13.2 g
      CO(2)/100 g fly ash with no water added and 18.5 g CO(2)/100 g fly ash with 20%
      water added. After accelerated carbonation, the C and O contents increased,
      indicating CO(2) capture in the fly ash; CO(2) combines with Ca(OH)(2) to form
      CaCO(3), which increased the CaCO(3) content from 12.5 to 54.3%. The leaching of
      Pb markedly decreased from 24.48 to 0.111 mg/L.

PMID- 19576669
TI  - "Why doesn't she seek help for partner abuse?" An exploratory study with South
      Asian immigrant women.
AB  - This study explores why South Asian immigrant women with experiences of partner
      abuse delay seeking help from professionals. Three focus groups were conducted in
      Hindi language with South Asian immigrant women in Toronto. Twenty-two women
      participated with a mean age of 46 years (range 29-68 years). Thematic analysis
      was conducted on the transcribed data using constant comparison techniques within
      and across the groups. We found that three major themes emerged from the
      discussions: reasons for delayed help-seeking, turning points and talking to
      professionals. Women expressed delaying help-seeking to the point when "Pani sar
      se guzar jata he" (water crosses over your head). Their dominant reasons for
      delayed help-seeking were social stigma, rigid gender roles, marriage
      obligations, expected silence, loss of social support after migration and limited
      knowledge about available resources and myths about partner abuse. Women usually
      turned for help only after experiencing pronounced mental and physical health
      problems. The findings are interpreted in light of participants' immigration
      context and the socio-cultural norms of patriarchy, collectivism and familism.
      Prevention approaches to address partner abuse and delayed help-seeking among
      South Asian immigrant women should include tailored community education, social
      services to reduce vulnerability, and cultural competency of professionals.
      Further research and program evaluation is needed to advance the field.

PMID- 19576670
TI  - Research on social capital and health in Japan. A commentary on Ichida and on
      Fujisawa.

PMID- 19576671
TI  - Preventing mother-to-child transmission of HIV in Vietnam and Indonesia:
      diverging care dynamics.
AB  - How do women and frontline health workers engage in preventing mother-to-child
      HIV transmission (PMTCT) in urban areas of Vietnam and Indonesia, where HIV is
      highly stigmatized and is associated with injecting drug use and sex work? This
      qualitative study explores local dynamics of care, using a mix of observations,
      focus group discussions, and interviews. In Indonesia the study was conducted in
      a community-based PMTCT program run by an NGO, while in Vietnam the study
      explored the care dynamics in routine PMTCT services, implemented by district and
      provincial public health facilities. In both of these PMTCT arrangements (the
      routine provider initiated approach in Vietnam and a more client-oriented system
      in Indonesia), pregnant women value the provision of HIV tests in antenatal care
      (ANC). Concerns are raised, however, by the unhappy few who test positive. These
      women are unsatisfied with the quality of counselling, and the failure to provide
      antiretroviral treatments. Acceptability of HIV testing in ANC is high, but the
      key policy issue from the perspective of pregnant women is whether the PMTCT
      services can provide good quality counselling and the necessary follow-up care.
      We find local level providers of PMTCT are pleased with the PMTCT program. In
      Vietnam, the PMTCT program offers health workers protection against HIV, since
      they can refer women away from the district health service for delivery. In
      Indonesia, community cadres are pleased with the financial incentives gained by
      mobilizing clients for the program. We conclude that achieving the global aims of
      reducing HIV infections in children by 50% requires a tailoring of globally
      designed public health programs to context-specific gendered transmission
      pathways of HIV, as well as local opportunities for follow-up care and social
      support.

PMID- 19576672
TI  - Transverse diffusivity of cerebral parenchyma predicts visual tracking
      performance in relapsing-remitting multiple sclerosis.
AB  - This study investigated the relation between cerebral damage related to multiple
      sclerosis (MS) and cognitive decline as determined by two classical mental
      tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was
      measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal
      and transverse diffusivity were defined in the cerebral parenchyma. Cognitive
      performance of the MS patients was assessed with the oral response format of the
      Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test
      (PASAT). A significant correlation was found between performance on the SDMT and
      the fractional anisotropy in the brain. This correlation was predominantly
      induced by transverse diffusivity. Transverse diffusivity refers to the diffusion
      across fibers rather than along the fibers and is believed to be a specific
      marker for axonal loss and demyelination associated with MS. No significant
      association between DTI-measures and PASAT performance was found and this
      negative finding was mainly attributed to psychometric qualities. These results
      indicate that diffusivity along the non-principal diffusion direction, a possible
      signature of MS-related white matter pathology, contributes to information
      processing speed as measured with the SDMT, a task that requires close visual
      tracking and a widely used clinical marker for cognitive decline in MS.

PMID- 19576673
TI  - The relationship of alcohol dependence and alcohol consumption with
      periodontitis: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the studies about
      the relationship of alcohol dependence and alcohol consumption with
      periodontitis. DATA AND SOURCES: A comprehensive search was performed in the
      Systematic Eletronic (PUBMED Medline, Latin American and Caribean Health Science
      LILACS, Scientific electronic library online-SciELO and Cochrane Central Register
      of Controlled Trials-CCRT literature databases) from January 1965 to July 2008.
      The reference lists of the identified studies were also searched. RESULTS: Of the
      1530 papers identified, 11 cross-sectional and 5 longitudinal observational
      studies met the inclusion criteria. Seven of the 12 studies on alcohol
      consumption and 4 of the 4 studies on alcohol dependence reported positive
      associations between alcohol intake and periodontitis. There was heterogeneity
      among studies concerning the methods of assessment of alcohol dependence, alcohol
      consumption and periodontitis. Therefore no meta-analysis was performed. Although
      smoking was properly addressed in all selected studies, the confounding effect of
      dental plaque was taken into account in only 6 studies. CONCLUSION: Alcohol
      consumption can be considered a risk indicator for periodontitis. Longitudinal
      studies on the association of alcohol dependence and alcohol consumption with
      periodontitis are needed to confirm the association or not.

PMID- 19576674
TI  - Life threatening ventricular fibrillation--an initial manifestation of Graves'
      disease.

PMID- 19576675
TI  - The O-sign.

PMID- 19576676
TI  - Alternating providers during continuous chest compressions for cardiac arrest:
      every minute or every two minutes?
AB  - Studies have shown that the quality of chest compressions for cardiac arrest
      decreases markedly after only a brief time. This is thought to be an important
      contributor to an adverse outcome of resuscitation, which has led to
      recommendations to alternate chest compression providers. This study compared
      alternating rescuers every 1 min versus every 2 min in a manikin simulation.
      Forty pairs of rescuers were randomly assigned to either scenario. The main
      outcome measure was the number of effective compressions. The results were
      analysed using one-way analysis of variance. Over the full 8 min, no significant
      difference was found in the number of effective chest compressions (p=0.707).
      Furthermore, no significant difference was found when comparing each 2 min block.
      An explanation for this may be that the compressions lost due to fatigue in the 2
      min scenario are approximately offset by compressions lost due to the
      practicalities of changing over. Power calculations with these results show that
      an unfeasibly large number of scenarios would be needed to definitively
      demonstrate the superiority of one of the scenarios. It seems reasonable to
      alternate chest compression providers every 2 min, to prevent the loss of
      effective compressions due to fatigue and to minimise interruptions of chest
      compressions. The ideal time to do this would be during the rhythm and pulse
      check as dictated by current guidelines.

PMID- 19576677
TI  - Breast Cancer in Pregnancy: report of 12 cases.

PMID- 19576678
TI  - DNA-binding geometry dependent energy transfer from 4',6-diamidino-2-phenylindole
      to cationic porphyrins.
AB  - The circular and linear dichroism (CD and LD) spectral properties of the meso
      tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP)-DNA complex at a
      [porphyrin]/[DNA] ratio below 0.015 showed that TMPyP intercalates between DNA
      base pairs. Contrarily, when cis-bis(N-methylpyridinium-4-yl)porphyrin (BMPyP) is
      associated with DNA, no CD spectrum was induced and a bisignate LD spectrum was
      observed. These spectral properties of both the TMPyP and BMPyP were essentially
      retained when the minor groove of the DNA was saturated with 4',6-diamidino-2
      phenylindole (DAPI). The fluorescence of the DNA-bound DAPI was effectively
      quenched by BMPyP and TMPyP. The quenching by BMPyP can be described through a
      pure static mechanism while TMPyP quenching produced an upward bending curve in
      the Stern-Volmer plot. Quenching efficiency was by far greater than predicted by
      the "sphere of action model", suggesting that the DNA provides some additional
      processes for an effective energy transfer.

PMID- 19576679
TI  - Biosorption of Cu(2+) and Zn(2+) from aqueous solutions by dried marine green
      macroalga Chaetomorpha linum.
AB  - The biosorption of the heavy metals Cu(2+) and Zn(2+) by dried marine green
      macroalga (Chaetomorpha linum) was investigated. The biosorption capacities of
      the dried alga for copper and zinc were studied at different solution pH values
      (2-6), different algal particle sizes (100-800microm) and different initial metal
      solution concentrations (0.5-10mM). An optimum pH value of 5 was found suitable
      for both metal ions biosorption for both metal ions. At the optimum particle size
      (100-315microm), biosorbent dosage (20g/l) and initial solution pH (pH 5), the
      dried alga produced maximum copper and zinc uptakes values (q(max)) of 1.46 and
      1.97mmol/g respectively (according to the Langmuir model). The kinetic data
      obtained at different initial metal concentrations indicated that the biosorption
      rate was fast and most of the process was completed within 120min. This study
      illustrated an alternative technique for the management of unwanted biological
      materials using processed algal material. C. linum is one of the fast-growing
      marine algae in the lake of Tunis and could be utilized as a biosorbent for the
      treatment of Cu(2+) and Zn(2+) contaminated wastewater streams.

PMID- 19576680
TI  - Drain-blocking techniques on blanket peat: A framework for best practice.
AB  - In recent years there has been a dramatic increase in artificial drain-blocking
      in world peatlands. The UK blanket peatlands have been severely drained over the
      past few decades but now drains are being blocked in an attempt to improve
      peatland environments. The drain-blocking has been a disparate process with
      limited knowledge transfer between organisations and within organisations
      operating in different geographic areas. Consequently, there has been no
      compilation of techniques used and their effectiveness. During this study thirty
      two drain-blocked sites were surveyed and all the key stakeholders interviewed.
      Drain-blocking using peat turf was preferred by practitioners and was also the
      most cost-effective method. Peat turves were successful except on steep slopes,
      in areas of severe erosion, in very wet or very dry locations, or if the mineral
      substrate was exposed. A drain-blocking best practice guide is offered by this
      paper, providing information on the most suitable methods for blocking peatland
      drains under different circumstances. Additional considerations are provided for
      practitioners to ensure peatland drain-blocking is as successful as possible.

PMID- 19576681
TI  - Technique of laparoscopic-endoscopic single-site surgery radical nephrectomy.
AB  - BACKGROUND: Laparoscopic-endoscopic single-site surgery (LESS) represents the
      closest surgical technique to scar-free surgery. OBJECTIVE: To assess the
      feasibility of LESS radical nephrectomy (LESS-RN). DESIGN, SETTING, AND
      PARTICIPANTS: Ten patients with body mass index (BMI) < or = 30 underwent LESS-RN
      for renal tumour by two experienced laparoscopists. SURGICAL PROCEDURE: TriPort
      (Olympus Winter & Ibe, Hamburg, Germany) was inserted through a transumbilical
      incision. A combination of standard laparoscopic instruments and flexible grasper
      and scissors was used. A 5-mm 30 degrees camera was also used. The standard
      laparoscopic transperitoneal nephrectomy technique was performed. MEASUREMENTS:
      Patient demographics, operative details, and final pathology were prospectively
      recorded. Postoperative evaluation of pain and use of analgesic medication were
      recorded. RESULTS AND LIMITATIONS: Ten cases were successfully accomplished (two
      right-sided tumours and eight left-sided tumours; tumour diameter ranges: 4-8
      cm). The mean patient age was 63.5 yr (22-77 yr), and median BMI was 23.56 (18.2
      26.6). The mean operative time was 146.4 min (120-180 min), and the mean blood
      loss was 202 ml (50-900 ml). Pathological examination observed organ-confined T1
      renal cell carcinoma in nine cases and pT3b tumour in one case. One bleeding
      complication occurred. Limitations regarding the intraoperative instrument
      ergonomics and the requirement for ambidexterity of the surgeon were noted.
      CONCLUSIONS: LESS-RN proved to be safe and feasible. Further clinical
      investigation in comparison to the established techniques should take place to
      evaluate the outcome of LESS-RN.

PMID- 19576682
TI  - Recurrence and progression of disease in non-muscle-invasive bladder cancer: from
      epidemiology to treatment strategy.
AB  - CONTEXT: This review focuses on the prediction of recurrence and progression in
      non-muscle invasive bladder cancer (NMIBC) and the treatments advocated for this
      disease. OBJECTIVE: To review the current status of epidemiology, recurrence, and
      progression of NMIBC and the state-of-the art treatment for this disease.
      EVIDENCE ACQUISITION: A literature search in English was performed using PubMed
      and the guidelines of the European Association of Urology and the American
      Urological Association. Relevant papers on epidemiology, recurrence, progression,
      and management of NMIBC were selected. Special attention was given to fluorescent
      cystoscopy, the new World Health Organisation 2004 classification system for
      grade, and the role of substaging of T1 NMIBC. EVIDENCE SYNTHESIS: In NMIBC,
      approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma
      in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of
      cancer in western society and the most expensive cancer per patient. Recurrence
      (in < or = 80% of patients) is the main problem for pTa NMIBC patients, whereas
      progression (in < or = 45% of patients) is the main threat in pT1 and CIS NMIBC.
      In a recent European Organisation for Research and Treatment of Cancer analysis,
      multiplicity, tumour size, and prior recurrence rate are the most important
      variables for recurrence. Tumour grade, stage, and CIS are the most important
      variables for progression. Treatment ranges from transurethral resection (TUR)
      followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes,
      re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients
      to early cystectomy for treatment-refractory high-risk NMIBC. CONCLUSIONS: NMIBC
      is a heterogeneous disease with varying therapies, follow-up strategies, and
      oncologic outcomes for an individual patient.

PMID- 19576683
TI  - Coexistence of cerebral aneurysm and meningioma--pure accident?
AB  - OBJECTIVES: Coexisting intracerebral aneurysms and meningiomas occur relatively
      rarely, without a clear relationship, although an aneurysm can be located within
      a meningioma. The aim of this retrospective study was to identify possible
      explanations for the coexistence of these conditions and to present a rationale
      for treatment strategies. PATIENTS AND METHODS: Ninety-five patients with
      coexistent meningioma and aneurysm were found in the National Library of
      Medicine, and 11 more patients were retrieved from our own database. RESULTS: Co
      occurrence of both pathologies, sometimes solitary, sometimes multiple, was
      mostly found in women (3:1). Clinical symptoms in the majority of patients were
      caused by tumour growth, whereas aneurysm rupture was seen only in a few cases.
      Consequently tumour resection was performed first in 58 out of the 95 patients,
      and aneurysm treatment in 38 patients. From available data, the mortality rate
      three decades before was approximately 40%, but decreased in the last years, due
      to microsurgical and endovascular techniques. All of our patients were alive
      after 1 year of follow-up. In patients with intratumoural aneurysms, only three
      published and one our own case, were treated for both pathologies. CONCLUSIONS:
      The coexistence of meningioma and aneurysm seems to be a coincidence. Treatment
      should primary focus on the cause of presenting symptoms, but in cases with
      intratumoural aneurysm, the aneurysm should be treated first. Due to the
      development of microsurgical and endovascular techniques peri-procedural
      mortality and morbidity has decreased.

PMID- 19576684
TI  - p53 Codon 72 polymorphism is associated with occurrence of cervical carcinoma in
      the Chinese population.
AB  - We investigated the genotype distribution of the p53 Arg72Pro polymorphisms in
      500 cervical carcinoma and 800 normal women in Chinese population. HPV infection
      rates in carcinoma patients and control were 89.4% and 31.0%. Women carrying the
      p53 Arg72Pro or p53 Pro72Pro increased the risk of cervical carcinoma (ORs and
      95% CIs being 3.74 (2.65-5.30), 2.23 (1.49-3.34)). In HPV positive population,
      elevated risks were also associated with p53 Arg72Pro, Pro72Pro (ORs and 95% CIs
      being 3.83 (2.02-7.24), 2.38 (1.14-4.99)). These results suggest that a proline
      in position 72 of p53 increases the risk of cervical carcinoma in Chinese
      population.

PMID- 19576685
TI  - The economy of oil spills: direct and indirect costs as a function of spill size.
AB  - As a rational basis for addressing both ecological and economic consequences of
      oil spills, a combination of simulating and estimating methods is proposed in
      this paper. An integration of the state-of-the-art oil spill contingency
      simulation system OSCAR with economic assessment method leads to realistic oil
      spill scenarios including their biological and economic impacts and the effort
      taken for combat as well as to an estimate for the total oil spill costs. In
      order to derive a simple function of total costs depending on few spill
      characteristics such as size, a number of hypothetical scenarios are simulated
      and evaluated for the German North Sea area. Results reveal that response costs
      of per unit oil spilled as well as integrated costs of oil released are simply
      characterized as two particular power-law functions of spill size. Such
      relationships can be straightforward transferred into decision making for
      efficient prevention and combat strategy in the study area.

PMID- 19576686
TI  - Effectiveness of compost use in salt-affected soil.
AB  - Soil degradation and salinization are two of the utmost threat affecting
      agricultural areas, derived from the increasing use of low quality water and
      inappropriate cultural practices. The problem of low productivity of saline soils
      may be ascribed not only to their salt toxicity or damage caused by excess
      amounts of soluble salts but also arising from the lack of organic matter and
      available mineral nutrients especially N, P, and K. Concerns about salinization
      risk and environmental quality and productivity of agro-ecosystems have
      emphasized the need to develop management practices that maintain soil resources.
      Composted municipal solid waste (MSW) was commonly used to enhance soil
      productivity in the agricultural lands and rebuild fertility. However, their
      application could be also a promising alternative to alleviate the adverse
      effects caused by soil salinization. MSW compost, with high organic matter
      content and low concentrations of inorganic and organic pollutants allow an
      improvement of physical, chemical and biochemical characteristics and constitute
      low cost soil recovery.

PMID- 19576687
TI  - Total oxidation of naphthalene with high selectivity using a ceria catalyst
      prepared by a combustion method employing ethylene glycol.
AB  - During the catalytic combustion of naphthalene, compounds other than CO(2) are
      often obtained. These products, as polymerized polycyclic aromatic hydrocarbons,
      oxygenated aromatic compounds and benzene derivate compounds, are usually more
      toxic than naphthalene. At the present work it is shown a nanocrystalline cerium
      oxide prepared by a combustion method employing a proper ethylene glycol
      concentration that exhibits very high activity in the decomposition of
      naphthalene in the presence of air and, most importantly, a selectivity value
      towards CO(2) of 100% for any range of conversions and/or temperatures used. In
      addition, it has been demonstrated that the amount of ethylene glycol employed in
      the synthesis of the catalyst is determinant to achieve the optimal catalytic
      performance. The catalytic results have been explained in terms of the amount of
      cerium oxide defects.

PMID- 19576688
TI  - A parametric comparative study of electrocoagulation and coagulation using
      ultrafine quartz suspensions.
AB  - This paper attempts to compare electrocoagulation using aluminum anodes and
      stainless steel cathodes with conventional coagulation by aluminum sulfate dosing
      on aqueous suspensions of ultrafine quartz. Several key parameters affecting the
      efficiency of electrocoagulation and coagulation were investigated with
      laboratory scale experiments in search of optimal parameter values. Optimal
      values of the parameters were determined on the basis of the efficiency of
      turbidity removal from ultrafine quartz suspensions. The parameters investigated
      in the study were suspension pH, electrical potential, current density,
      electrocoagulation time, and aluminum dosage. A comparison between
      electrocoagulation and coagulation was made on the basis of total dissolved
      aluminum, revealing that electrocoagulation and coagulation were equally
      effective at the same aluminum dosage for the removal of quartz particles from
      suspensions. Coagulation, however, was more effective in a wider pH range (pH 6
      9) than electrocoagulation which yielded optimum effectiveness in a relatively
      narrower pH range around 9, where, in both methods, these pH values corresponded
      to near-zero zeta potentials of quartz particles. Furthermore, experimental
      results confirmed that electrocoagulation could display some pH buffering
      capacity. The kinetics of electrocoagulation was very fast (<10 min) in
      approaching a residual turbidity, which could be modeled with a second-order rate
      equation.

PMID- 19576689
TI  - Phyto-crystallization of palladium through reduction process using Cinnamom
      zeylanicum bark extract.
AB  - In this paper we studied the potential of nanocrystalline palladium particle
      production using Cinnamom zeylanicum bark extract (CBE) as the biomaterial for
      the first time. We studied the effects of biomaterial dosage, pH and temperature
      on nanoparticle formation; none of these factors had a major effect on the size
      and shape of the nanoparticles formed. Transmission electron microscopy (TEM)
      observations confirmed the synthesis of nano-sized palladium particles. More or
      less uniformly sized palladium nanoparticles were synthesized with an average
      size ranging from 15 to 20 nm. It was found that the zeta potential of these
      formed palladium nanoparticles was negative, and that it increased with an
      increase in pH. Energy dispersive X-ray (EDX) analysis results confirmed the
      significant presence of palladium. Of the palladium ions, 60% were reduced to a
      zero valent form by CBE. Terpenoids are believed to play an important role in
      palladium nanoparticle biosynthesis through the reduction of palladium ions.
      Currently, however, the exact mechanism for the synthesis of palladium
      nanoparticles is unclear. Our protocol for the phyto-synthesis of palladium
      nanoparticles under moderate pH and room temperature offers a new means to
      develop environmentally benign nanoparticles.

PMID- 19576690
TI  - Bioaugmentation of a sequencing batch reactor with Pseudomonas putida ONBA-17,
      and its impact on reactor bacterial communities.
AB  - This study demonstrates the feasibility of using Pseudomonas putida ONBA-17 to
      bioaugment a sequencing batch reactor (SBR) treating o-nitrobenzaldehyde (ONBA)
      synthetic wastewater. To monitor its survival, the strain was chromosomally
      marked with gfp gene. After a transient adaptation, almost 100% degradation of
      ONBA was obtained within 8 days as compared with 23.47% of the non-inoculated
      control. The bioaugmented reactor has a better chemical oxygen demand (COD)
      removal performance (96.28%) than that (79.26%) of the control. The
      bioaugmentation not only enhanced the removal capability of target compound, but
      shortened system start-up time. After the increase in ONBA load, performance
      fluctuation of two reactors was observed, and the final treating effects of them
      were comparable. What is more, denaturing gradient gel electrophoresis (DGGE)
      analysis of 16S rRNA genes via a combination of pattern comparison and sequence
      phylogenetic analysis was performed to uncover changes in sludge microbial
      communities. Only the members of alpha, beta and gamma subdivisions of
      Proteobacteria were identified. To isolate ONBA-degrading relevant
      microorganisms, spread plate was used and four bacterial strains were obtained.
      Subsequent systematic studies on these bacteria characterized their traits which
      to some extent explained why such bacteria could be kept in the system. This
      study will help future research in better understanding of the bioreactor
      bioaugmentation.

PMID- 19576691
TI  - Characterisation of oxidised aluminium powder: validation of a new anodic
      oxidation bench.
AB  - Aluminium powder is of major interest in many applications but it presents a risk
      due to its high explosibility, particularly when dispersed in air. The safety is
      directly linked to the particles oxidation because the Minimum Ignition Energy
      (MIE), which is required to initiate an Al dust explosion, increases with the
      oxide layer thickness. This study provides a controlled method to furnish
      reproducible homogeneous set of powder for such safety studies. Thanks to a new
      experimental bench, the influence on the oxidation rate of seven treatment
      parameters is investigated (current density, time of treatment, acid
      concentration, mass of powder, particles size, stirring, neutralisation by
      ammonia solution). The oxide content is plotted versus the current density, the
      time and the acid concentration to provide reference curves for further
      elaboration of oxidised powder. The particles size of sieved powder is measured
      before and after treatment by different methods (optical and Scanning Electron
      Microscopes, laser measurement). A high refinement of the powder in terms of size
      distribution is achieved thanks to the employed sieving. The present bench and
      the elaborated procedure are of great interest to provide well-calibrated
      oxidised powder directly available for safety studies. The time must be adjusted,
      depending on the wanted oxide content--from 2 to 18 wt.% - and the other
      treatment parameters must be kept constant: acid concentration (5 wt.%), current
      density (1 Adm(-2)), treated powder (20 g). In these conditions, the ratio of the
      oxide layer thickness on the particles diameter is found to be constant for a
      given oxide content whatever the particles size.

PMID- 19576692
TI  - Nickel adsorption by sodium polyacrylate-grafted activated carbon.
AB  - A novel sodium polyacrylate grafted activated carbon was produced by using gamma
      radiation to increase the number of functional groups on the surface. After
      irradiation the capacity for nickel adsorption was studied and found to have
      increased from 44.1 to 55.7 mg g(-1). X-ray absorption spectroscopy showed that
      the adsorbed nickel on activated carbon and irradiation-grafted activated carbon
      was coordinated with 6 oxygen atoms at 2.04-2.06 A. It is proposed that this
      grafting technique could be applied to other adsorbents to increase the
      efficiency of metal adsorption.

PMID- 19576693
TI  - Hazardous potential of manufactured nanoparticles identified by in vivo assay.
AB  - New products of nanotechnologies, including nanoparticles, need to be assessed
      according to their biological reactivity and toxic potential. Given the large
      number of diverse nanomaterials, a tiered approach is favoured. The aim of our
      work presented here is to elaborate an in vivo assay with terrestrial
      invertebrates (Porcellio scaber), which could serve as a first step of hazard
      identification of nanoparticles. We adapted the widely used acridine
      orange/ethidium bromide (AO/EB) assay to be applicable for cell membrane
      stability assessment of entire organ where the animal was exposed in vivo. The
      digestive glands (hepatopancreas) of terrestrial isopods were taken as a model
      test system. The assay was validated with Cu(NO(3))(2) and surfactants. The
      results showed that all tested nanoparticles, i.e. nanosized TiO(2), nanosized
      ZnO and fullerenes (C(60)) have cell membrane destabilization potential. As
      expected, C(60) is the most biologically potent. The AO/EB in vivo assay proved
      to be fast because response is recorded after 30 min of exposure, relatively
      simple because digestive glands are inspected immediately after isolation from
      exposed animals and promising approach because different types of nanoparticles
      could be tested for their biological potential. This assay provides data for the
      identification of hazardous potential of nanoparticles before subsequent steps in
      a tiered approach are decided.

PMID- 19576694
TI  - Removal of mercury(II) from aqueous solution using moss (Drepanocladus revolvens)
      biomass: equilibrium, thermodynamic and kinetic studies.
AB  - The equilibrium, thermodynamics and kinetics of the biosorption of Hg(II) onto
      moss (Drepanocladus revolvens) biomass from aqueous solution were investigated.
      Optimum experimental parameters were determined to be pH 5.5, contact time 60min,
      biomass concentration 4 g L(-1) of solution, and temperature 20 degrees C. From
      the Langmuir model the maximum biosorption capacity of the moss biomass was found
      to be 94.4 mg g(-1). The mean free energy value (10.2 kJ mol(-1)) evaluated by
      using the Dubinin-Radushkevich (D-R) model indicated that the biosorption of
      mercury ions onto D. revolvens was taken place by chemical ion-exchange. The
      kinetic studies indicated that the biosorption process of mercury ions followed
      well pseudo-second-order model. The calculated thermodynamic parameters (DeltaG
      degrees , DeltaS degrees , DeltaH degrees ) showed the biosorption to be
      exothermic and spontaneous with decreased randomness at the solid-solution
      interface. The recovery of the Hg(II) from D. revolvens biomass was found to be
      99% using 1M HCl. It was concluded that the D. revolvens biomass can be used as
      biosorbent for the treatment of wastewaters containing Hg(II) ions.

PMID- 19576696
TI  - An efficient approach to characterize pseudo-merohedral twins by precession
      electron diffraction: application to the LaGaO(3) perovskite.
AB  - Pseudo-merohedral twins are frequently observed in crystals displaying pseudo
      symmetry. In these crystals, many [u v w] zone axis electron diffraction patterns
      are very close and can only be distinguished from intensity considerations. On
      conventional diffraction patterns (selected-area electron diffraction or
      microdiffraction), a strong dynamical behaviour averages the diffracted
      intensities so that only the positions of the reflections on a pattern can be
      considered. On precession electron diffraction patterns, the diffracted beams
      display an integrated intensity and a "few-beam" or "systematic row" behaviour
      prevails which strongly reduces the dynamical interactions. Therefore the
      diffracted intensity can be taken into account. A procedure based on observation
      of the weak extra-reflections connected with the pseudo-symmetry is given to
      identify without ambiguity any zone axis. It is successfully applied to the
      identification and characterization of {1 2 1} reflection twins present in the
      LaGaO(3) perovskite.

PMID- 19576695
TI  - Concerns about the use of colour doppler in the diagnosis of pudendal nerve
      entrapment.

PMID- 19576697
TI  - First-line chemotherapy of non-seminomatous germ cell tumors(NSGCTs).
AB  - Germ cell tumors (GCTs) account for the majority of testicular cancer cases
      occurring in men of young age and are divided into two main histologic groups,
      seminomas and non-seminomas. The introduction of cisplatin in the treatment of
      germ cell tumors was a breakthrough, classifying them among curable diseases. The
      identification of 3 subgroups of patients with non-seminomatous tumors (good
      risk, intermediate and poor-risk), with different profiles concerning prognosis
      and response to treatment, supported clinical trials aiming to assess different
      treatment strategies and recommend the most effective and less toxic regimens.
      This review describes the toxic effects of therapy and the efforts aiming to
      overcome toxicity and improve treatment efficacy, focusing on the trials which
      form the basis of current standard treatment of non-seminomatous germ cell
      tumors.

PMID- 19576698
TI  - Oral phycocyanobilin may diminish the pathogenicity of activated brain microglia
      in neurodegenerative disorders.
AB  - There is considerable evidence that activated microglia play a central role in
      the pathogenesis of many prominent neurodegenerative disorders, including
      Parkinson's and Alzheimer's diseases. The elevated NADPH oxidase activity of
      these microglia contributes importantly to their pathogenic impact, collaborating
      with increased iNOS activity to generate the cytotoxic oxidant peroxynitrite.
      Phycocyanobilin (PCB), a chromophore derived from biliverdin that constitutes up
      to 1% of the dry weight of spirulina, has recently been shown to be a potent
      inhibitor of NADPH oxidase. The possibility that orally administered PCB could
      reach the brain parenchyma in sufficient concentrations to influence microglial
      function is consistent with the findings of two rodent studies: orally
      administered C-phycocyanin (the spirulina holoprotein that includes PCB)
      suppresses the neurotoxic impact of the excitotoxin kainite in rats, and a diet
      high in spirulina ameliorates the loss of dopaminergic neurons in the MPTP
      induced Parkinsonian syndrome in mice. Hence, supplemental PCB may have
      considerable potential for preventing or slowing the progression of a range of
      neurodegenerative disorders. Some of the central physiological effects of PCB may
      also reflect inhibition of neuronal NADPH oxidase, which is now known to have a
      modulatory impact on neuron function, and can mediate neurotoxicity in certain
      circumstances. Neuronal NADPH oxidase activation is an obligate mediator of the
      central pressor effect of angiotensin II, and there is suggestive evidence that
      it may also play a role in inflammatory hyperalgesia; these findings point to
      possible antihypertensive and analgesic applications for PCB. The likely
      favorable effects of PCB on vascular health may also protect the brain by
      decreasing stroke risk, and inhibition of NADPH oxidase in rodents has been shown
      to lessen the neurotoxic impact of temporary cerebral ischemia. PCB may thus have
      versatile potential for preserving the healthful function of the central nervous
      system into advanced old age--albeit optimal neuroprotection may require more
      complex regimens that incorporate PCB along with other well tolerated
      nutraceuticals and drugs, in conjunction with prudent lifestyle modifications.

PMID- 19576699
TI  - NADPH oxidase mediates glucolipotoxicity-induced beta cell dysfunction--clinical
      implications.
AB  - An impairment of glucose-stimulated insulin secretion--reflecting decreased
      glucokinase expression--and a moderate decrease in beta cell mass attributable to
      increased apoptosis, constitute the key features of beta cell failure in type 2
      diabetes. Oxidative stress, provoked by prolonged exposure to excessive levels of
      glucose and/or fatty acids (glucolipotoxicity), appears to be a key mediator of
      these defects. Oxidant-provoked JNK activation induces nuclear export of the PDX
      1 transcription factor, required for expression of glucokinase and other beta
      cell proteins. Conversely, increases in cAMP induced by incretin hormones promote
      the nuclear importation of PDX-1, counteracting the diabetogenic impact of
      oxidant stress; this may explain the utility of measures that slow dietary
      carbohydrate absorption for diabetes prevention. The ability of oxidative stress
      to boost apoptosis in beta cells is poorly understood, but may also entail JNK
      activation. Recent work establishes a phagocyte-type NADPH oxidase as the chief
      source of glucotoxicity-mediated oxidative stress in beta cells. Since bilirubin
      is now known to function physiologically as an inhibitor of NADPH oxidase, and
      phycocyanobilin (PCB) derived from spirulina likewise can inhibit this enzyme
      complex, supplemental PCB may have utility in the prevention and control of
      diabetes, and Gilbert syndrome, associated with chronically elevated free
      bilirubin, may be associated with decreased diabetes risk.

PMID- 19576701
TI  - Interventions for recurrent/persistent carpal tunnel syndrome after carpal tunnel
      release.

PMID- 19576700
TI  - Elbow position affects distal radioulnar joint kinematics.
AB  - PURPOSE: Previous in vivo and in vitro studies of forearm supination-pronation
      suggest that distal radioulnar joint kinematics may be affected by elbow flexion.
      The primary hypotheses tested by this study were that, in vivo, ulnar variance
      changes with elbow flexion and forearm rotation, and the arc of forearm rotation
      changes in relationship to elbow flexion. METHODS: Changes in radioulnar
      kinematics during forearm supination-pronation and elbow flexion (0 degrees to 90
      degrees ) were studied in 5 uninjured subjects using computed tomography, dual
      orthogonal fluoroscopy, and 3-dimensional modeling. Analysis of variance and post
      hoc testing was performed. RESULTS: Proximal translation of the radius was
      greatest with the elbow flexed to 90 degrees with the arm in midpronation. With
      the arm in midpronation, the translation of the radius was significantly greater
      at 0 degrees versus 45 degrees of elbow flexion (0.82 +/- 0.59 mm vs 0.65 +/-
      0.80 mm, F: 4.49, post hoc: 0.055; p = .05) and significantly smaller at 45
      degrees versus 90 degrees of elbow flexion (0.65 +/- 0.80 mm vs 0.97 +/- 0.35 mm,
      F: 4.49, post hoc: 0.048; p = .05). Proximal translation of the radius in
      midpronation was significantly greater than when the forearm was in a supinated
      position when the elbow was at 0 degrees or 90 degrees flexion (F: 14.90, post
      hoc: <0.01; p < .01, F: 19.11, post hoc: <0.01, p < .01). The arc of forearm
      rotation was significantly decreased at 0 degrees compared with 90 degrees of
      elbow flexion (129.3 degrees +/- 22.2 degrees vs 152.8 degrees +/- 14.4 degrees ,
      F: 3.29, post hoc: 0.79; p = .09). The center of rotation shifted volarly and
      ulnarly with increasing elbow extension. CONCLUSIONS: Elbow position affects the
      kinematics of the distal radioulnar joint. The kinematics of the distal
      radioulnar joint are primarily affected by forearm rotation and secondarily by
      elbow flexion. These findings have clinical relevance to our understanding of
      ulnar impaction, and how elbow position affects the proximal-distal translation
      of the radius. These findings have implications for the treatment of ulna
      impaction, radiographic evaluation of the distal ulna, and future biomechanical
      studies.

PMID- 19576702
TI  - Versatility of the reverse dorsoulnar fasciocutaneous flap in coverage of hand
      defects: clinical experience with 36 cases.
AB  - PURPOSE: Local flap reconstruction is often required for soft tissue defects of
      the hand. The optimal reconstruction method should provide thin, supple, well
      vascularized tissue with minimal donor-site morbidity. Short operating time and a
      sizable pedicle for microsurgical anastomosis are helpful. In this study,
      outcomes of hand defects after reconstruction with a reverse dorsoulnar flap were
      retrospectively analyzed. METHODS: Between 2001 and 2008, 36 patients were
      evaluated (28 men, 8 women). Twenty-seven pedicle flaps and 9 free flaps were
      used. Nineteen patients had flexion contractures in their palms and fingers after
      burn injuries, 14 patients had traumatic soft tissue loss, and 3 patients had
      defects after tumor exicision. In 26 cases the defects were on the palm site, and
      in 10 cases the defects were on the dorsum of the hand. Mean follow-up was 12
      months. RESULTS: The success rate was 100%, with satisfactory cosmetic results.
      Functional recovery of the hands showed good results as well as acceptable donor
      healing without complication. CONCLUSIONS: The dorsoulnar flap as either pedicle
      or free flap provides good and reliable skin cover for substantial soft tissue
      defects on the palm, dorsum of the hand, and the fingers.

PMID- 19576703
TI  - [Pregnancy outcome in a group of Cameroonian women with uterine fibroids].
AB  - INTRODUCTION: Uterine fibroids are the most common benign tumor seen in women at
      reproductive age. The association of pregnancy and uterine fibroids is about 0.5
      to 4%. METHODOLOGY: In order to evaluate the complications of this association in
      our milieu, we carried out this prospective study. The main objective was to
      compare the incidence of complications of pregnancy and delivery in two groups of
      women: group 1 (women with uterine fibroids) and group 2 (women without
      fibroids). They were matched (ratio 1/1) on women age (plus or minus one),
      gestational age, gravidity (plus or minus one) and parity. RESULTS: Eighty
      patients in each group 1 were recruited. The mean age was 31.2 years in group 1
      and 30.8 years in group 2. Degeneration of fibroids occurred in 15% of cases. The
      incidence of threatened abortion (51.3% versus 18.8%; RR: 2.7 [1.7-4.5];
      p=0.00002), threaten premature delivery (26.3% versus 10%; RR: 2.6 [1.2-5.6];
      p=0.008), premature delivery (22.5% versus 7.9%; RR: 2.9 [1.2-6.9]), tocolytic
      treatment (48.8% versus 20.0%; RR: 2.4 [1.5-4.0]; p=0.0001) and Caesarean section
      (40% versus 13.8%; RR: 3.1 [1.6-5.9]; p=0.0001) were significantly increased in
      group 1 than in group 2. We also noticed a moderate increased of the incidence of
      abortions (11.3% versus 5%; RR: 2.3 [0.7-7.0]), breech presentation (11.3% versus
      5%; p=0.3); however, the difference was not statistically significant in two
      groups. CONCLUSION: We concluded that pregnancy in women with uterine fibroids is
      a high-risk pregnancy and needs a particular follow-up.

PMID- 19576704
TI  - Virulence of classical swine fever virus isolates from Europe and other areas
      during 1996 until 2007.
AB  - Classical Swine Fever (CSF) has caused several outbreaks in EU Member States with
      grave economic consequences. Several times the diagnosis of CSF was made too late
      partially due to non-specific clinical signs which did not raise suspicion for
      CSF. Virulence of CSF virus isolates (CSFV) still remains a subject of discussion
      and speculation as sufficient knowledge is still not available. Six
      uncharacterised CSFV isolates from 1996 to 2007 were assessed in animal
      experiments for their clinical virulence in order to broaden the knowledge about
      circulating CSFV and thereby assist disease eradication. A clinical (CS) and
      pathological score was applied and further extended by additional parameters to a
      modified CS (mCS) including case fatality, antibody production and leukocyte
      count. The unknown CSFV isolates could be classified as moderately or highly
      virulent. The inclusion of additional parameters, especially case fatality, into
      the mCS gave a more reliable classification of virulence, proving that there are
      clinical signs and laboratory parameters of blood which can be recognised.
      Therefore a subclinical course of infection is unlikely, especially in weaner
      pigs.

PMID- 19576705
TI  - Transmission of different variants of PCV2 and viral dynamics in a research
      facility with pigs mingled from PMWS-affected herds and non-affected herds.
AB  - Post-weaning Multisystemic Wasting Syndrome (PMWS) has been identified in most
      swine-producing countries worldwide. The disease has resulted in significant
      health challenges and economic damage to the swine industry. The aim of this
      study was to determine horizontal transmission of porcine circovirus type 2
      (PCV2) and to examine viral dynamics in pigs in a controlled PMWS transmission
      study. In the study pigs from PMWS-affected herds and non-affected herds were
      permitted to have close contact (same pen), nose-to-nose contact (to pigs in
      neighbouring pens) or no physical contact (pen across the aisle and pens in other
      compartments). By DNA sequence analysis, eight variants of genotype PCV-2b were
      identified in the research facility. From the spread of these PCV2-variants it
      was concluded that PCV2 primarily infects through close contact and nose-to-nose
      contact. PCV2 genome sequences were obtained from selected pigs at arrival to the
      research facility and again when the same pigs developed PMWS. This analysis
      showed that pigs from PMWS-affected herds developed PMWS caused by the same
      variant of PCV2 as they carried when entering the research facility. In contrast,
      pigs from non-affected herds developed PMWS with PCV2-variants identified in pigs
      from PMWS-affected herds. This was probably connected to at least 10(3) higher
      mean serum-titer of PCV2 in pigs from PMWS-affected herds as compared to pigs
      from non-affected herds at the beginning of the transmission study. The study
      further showed that pigs able to control the PCV2 infection, as measured by the
      PCV2-titer in serum, recovered clinically (pigs from PMWS-affected herds) or
      stayed healthy (pigs from non-affected herds). Like this, pigs with a PCV2 titer
      below 5x10(8) copies/ml serum during the study period had a chance of recover
      from the PCV2 infection whereas pigs with PCV2 titers above 5x10(8) copies/ml
      serum at any time point generally died from PMWS.

PMID- 19576706
TI  - Intergenerational birth weight associations by mother's birth order - the
      mechanisms behind the paradox: a population-based cohort study.
AB  - BACKGROUND: Mother's birth order is inversely associated with offspring birth
      weight despite positively associated with the mother's own birth weight. The
      causes behind this relation have not been elucidated. AIMS: To investigate the
      relation between mother's birth order and birth weight of her offspring, with
      emphasis on possible mechanisms behind the findings. STUDY DESIGN: Population
      based cohort study over two generations. SUBJECTS: Data were from the Medical
      Birth Registry of Norway, based on all births in Norway, 1967-2006 (2.3 million
      births). Units where both mothers and offspring were singletons and offspring
      were first born were included, forming 272,674 mother-offspring units for the
      analyses. OUTCOME MEASURE: Birth weight in the second generation. RESULTS:
      Mother's birth weight increased steadily with increasing birth order from 3369 g
      for first born to 3538 g for fourth or later born mothers. In contrast, there was
      a monotonic decrease in offspring mean birth weight with increasing mother's
      birth order (9.1 g per birth order (95% C.I.; 6.8, 11.4)). First born mothers
      tended to be older, to have higher education, to more often be married or
      cohabiting, and to smoke less than later born mothers at the time of their first
      pregnancy. CONCLUSION: The general reduction in mean birth weight among first
      born mothers was not observed in the next generation. We suggest that first born
      mothers have the same biologically potential for achieving similar sized
      offspring as later born mothers, and that social factors account for the inverse
      relation.

PMID- 19576707
TI  - Use of quantum dots in aqueous solution to detect blood fingermarks on non-porous
      surfaces.
AB  - A new and original reagent based on the use of highly fluorescent cadmium
      telluride (CdTe) quantum dots (QDs) in aqueous solution is proposed to detect
      weak fingermarks in blood on non-porous surfaces. To assess the efficiency of
      this approach, comparisons were performed with one of the most efficient blood
      reagents on non-porous surfaces, Acid Yellow 7 (AY7). To this end, four non
      porous surfaces were studied, i.e. glass, transparent polypropylene, black
      polyethylene, and aluminium foil. To evaluate the sensitivity of both reagents,
      sets of depleted fingermarks were prepared, using the same finger, initially
      soaked with blood, which was then successively applied on the same surface
      without recharging it with blood or latent secretions. The successive marks were
      then cut in halves and the halves treated separately with each reagent. The
      results showed that QDs were equally efficient to AY7 on glass, polyethylene and
      polypropylene surfaces, and were superior to AY7 on aluminium. The use of QDs in
      new, sensitive and highly efficient latent and blood mark detection techniques
      appears highly promising. Health and safety issues related to the use of cadmium
      are also discussed. It is suggested that applying QDs in aqueous solution (and
      not as a dry dusting powder) considerably lowers the toxicity risks.

PMID- 19576708
TI  - Detection of human blood by immunoassay for applications in forensic analysis.
AB  - The detection and confirmation of bloodstains as being human in origin is
      important in crime scene investigations. There are a number of blood detection
      methods currently available. The aim of this work was to develop an assay capable
      of detecting the presence of human blood from both liquid blood samples and dried
      bloodstains. A simple, direct competitive ELISA was developed utilising a
      polyclonal antibody against human IgG. Once optimised, the ELISA was found to be
      specific for human IgG, with no cross-reaction observed with pig, sheep, cow,
      goat, horse and rabbit IgG. The assay was also found to be sensitive, with a
      detection limit of 0.1 microg/mL. This compares favourably with leading blood
      detection methods. The assay was able to confirm the presence of human blood in
      blood mixtures, in stains on a variety of surfaces and also gave positive results
      with bloodstains that were up to 1 year old. The assay was simple to use, rapid
      and highly reproducible. The ELISA performance makes it suitable for development
      as a kit to rival currently used methods for the routine detection of human blood
      at crime scenes. Further applications of the anti-human IgG antibody are
      reported, including immunodot assays and a sandwich ELISA format. The methods
      described here are simple, reliable assays for the identification of human blood
      and are presented as viable alternatives to existing techniques for blood
      detection.

PMID- 19576709
TI  - The level of random background glass recovered from fleece jackets of individuals
      who worked in Law enforcement or related professions.
AB  - Fleece jackets are often encountered as items of clothing submitted for
      examination in forensic science laboratories in Scotland. This work examines the
      background glass contamination of garments of this nature in order to inform
      casework conclusions. 44 fleece jackets (100% polyester) from individuals who
      either worked in the Forensic Science laboratory or were police officers who
      regularly attended crime scenes were examined for the random presence of glass
      fragments. The refractive index of recovered fragments was determined using glass
      refractive index measurements. The values obtained were compared with glass
      fragments recovered from garments associated with criminal events and the results
      assessed.

PMID- 19576710
TI  - Long-term results of intranasal laser-assisted dacryocystorhinostomy with the use
      of a surgical microscope.
AB  - OBJECTIVE: To address the long-term results of our method that combines
      intranasal laser-assisted dacryocystorhinostomy with the use of surgical
      microscope. METHODS: The procedure is a modification of the West method. A
      retrospective series of the long-term results are presented in 105 patients that
      underwent 118 DCR procedures, over the past 6 years. Selection criteria were
      mainly acquired idiopathic nasolacrimal duct obstruction. RESULTS: 113 DCR cases
      (95.8%) were free of symptoms postoperatively (mean follow-up: 24 months).
      CONCLUSION: Our method when compared with traditional methods is correlated with
      excellent postoperative long-term results.

PMID- 19576711
TI  - The role of magnetic resonance imaging in determining the proximal extension of
      early stage cervical cancer to the internal os.
AB  - PURPOSE: To study the interobserver variability of MRI for visualization of the
      internal os and measuring the distance between tumor and the internal os in
      patients with early cervical carcinoma and to compare the distance between tumor
      and the internal os measured on MRI with invasion of the internal os determined
      by histopathology. MATERIALS AND METHODS: All T2-weighed MRI examinations between
      January 2003 and December 2007 of patients who underwent hysterectomy, of <=40
      years, with clinical stage IB1 cervix carcinoma and tumor size <=2cm were
      retrieved. 27 patients fulfilled these criteria. Two radiologists retrospectively
      reviewed the images for visualization of the internal os and the distance between
      tumor and the internal os; agreement and intraclass correlation coefficients
      (ICCs) were calculated to determine interobserver variability. The distance
      between tumor and the internal os measured on MRI was compared with invasion of
      the internal os determined by histopathology. RESULTS: In 26 patients,
      visualization of the internal was rated as good or moderate by both radiologists
      (agreement 96%). In 15 patients, both radiologists observed a tumor and the ICC
      for the distance between tumor and the internal os was 0.752 (95%CI: 0.406
      0.909). Assuming 5mm distance between tumor and the internal os on MRI as
      criterion for invasion of the internal os, 1 true-positive, 2 false-positives and
      none false-negatives were observed. Assuming 1cm as criterion increases the
      number of false-positives, respectively 3 and 5 by radiologist 1 and radiologist
      2. CONCLUSION: MRI has high interobserver values for visualization of the
      internal os and no false-negatives for involvement of the internal os.

PMID- 19576712
TI  - Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API
      intermediate using liquid-liquid extraction and GC-MS.
AB  - Dimethyl sulfate (DMS) is an alkylating reagent commonly used in organic
      syntheses and pharmaceutical manufacturing processes. Due to its potential
      carcinogenicity, the level of DMS in the API process needs to be carefully
      monitored. However, in-process testing for DMS is challenging because of its
      reactivity and polarity as well as complex matrix effects. In this short
      communication, we report a GC-MS method for determination of DMS in an API
      intermediate that is a methyl sulfate salt. To overcome the complex matrix
      interference, DMS and an internal standard, d6-DMS, were extracted from the
      matrix with methyl tert-butyl ether. GC separation was conducted on a DB-624
      column (30 m long, 0.32 mm ID, 1.8 microm film thickness). MS detection was
      performed on a single-quad Agilent MSD equipped with an electron impact source
      while the MSD signal was acquired in selected ion monitoring mode. This GC/MS
      method showed a linear response for DMS equivalent from 1.0 to 60 ppm. The
      practical quantitation limit for DMS was 1.0 ppm and the practical detection
      limit was 0.3 ppm. The relative standard derivation for analyte response was
      found as 0.1% for six injections of a working standard equivalent to 18.6 ppm of
      DMS. The spike recovery was ranged from 102.1 to 108.5% for a sample of API
      intermediate spiked with 8.0 ppm of DMS. In summary, the GC/MS method showed
      adequate specificity, linearity, sensitivity, repeatability and accuracy for
      determination of DMS in the API intermediate. This method has been successfully
      applied to study the efficiency of removing DMS from the process.

PMID- 19576713
TI  - Narghile (hookah) smoking and carboxyhemoglobin levels.

PMID- 19576714
TI  - Learning to cope with chronic illness. Efficacy of a multi-component treatment
      for people with chronic fatigue syndrome.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of an out-patient,
      multi-component programme developed for patients with chronic fatigue syndrome
      (CFS). METHODS: Twenty-two patients were assessed before and after six months of
      treatment. Findings were compared with 22 individuals on the waiting list. The
      programme offered medical care as well as information and counselling to help
      patients to understand, accept and cope with their illness. RESULTS: At six
      months, there were significant differences between the groups for fatigue, self
      efficacy and anxiety. Overall, 82% of the treated patients reported feeling
      better and 23% had improved to such a degree that they were discharged from the
      clinic. The gains were maintained at twelve months. CONCLUSION: This programme
      was found to be both helpful and acceptable and may provide a useful first-line
      intervention for many patients with CFS. PRACTICE IMPLICATIONS: Short, pragmatic
      programmes may be as effective as cognitive-behaviour therapy.

PMID- 19576716
TI  - Endovascular repair of traumatic aortic injury in a pediatric patient.
AB  - We present the case of a 14-year-old girl who sustained a traumatic aortic injury
      (TAI) after a motor vehicle collision. Due to the severity of her associated
      injuries, she was not a candidate for open aortic repair. Available options for
      endovascular repair were very limited due to the small aortic diameter (14 mm).
      We performed a successful endovascular repair with an off-label use of an iliac
      limb prosthesis (Excluder, WL Gore, Flagstaff, Ariz). This case demonstrates the
      utility of an iliac limb prosthesis for endovascular repair of TAI in a child as
      a bridge to future open conversion.

PMID- 19576715
TI  - Predictive factors of success following radio-frequency stylet (RFS) ablation of
      incompetent perforating veins (IPV).
AB  - OBJECTIVE: To evaluate potential predictive factors associated with success or
      failure of incompetent perforating veins (IPVs) treated with radio-frequency
      stylet (RFS). METHODS: Over the last 12 months in this observational study, 38
      consecutive patients with various degrees of venous insufficiency and IPVs
      underwent 48 office-based radio-frequency ablation procedures (1 - C 3; 7 - C 4;
      10 - C 5; 30 - C 6) in 44 limbs. There were 21 females and 17 males with a mean
      age of 67 +/- 17 years (38-93 years) who had a total of 93 IPVs (40 calf; 53
      ankle). Eighteen patients (47%) had ipsilateral great saphenous vein (GSV) radio
      frequency closures performed prior to current procedure. The venous flow pattern
      was classified by spectral waveform analysis as "normal" (spontaneous with
      respiratory phasicity) in 33 patients and "pulsatile" (with bidirectional cardiac
      phasicity) in five patients. Follow-up duplex scans were performed from 3 to 7
      days postprocedure. Statistical analyses were performed for determining
      correlation between the various factors such as, age, pulsatile flow, CEAP class,
      prior GSV ablation, vein diameter, reflux, and patency. RESULTS: The mean number
      of ablated IPVs was 1.94 +/- 0.38 ranging from 1-3. Immediate success rate was
      88% (82 cases, 32 patients). IPVs had a duplex measured mean diameter of 3.8 +/-
      1.1 mm (2-6.6 mm). Eleven IPVs remained patent in six patients. There was no
      significant difference between the patent and the obliterated IPV groups
      concerning age (P = 0.75), prior GSV ablation (P = .19), IPV diameter (P = .08)
      and CEAP classification. Conversely, four of the five procedures (80%) performed
      in patients with "pulsatile" venous flow failed, while only two of the remaining
      43 procedures (4.7%) in patients with "normal" venous flow failed (P < .001).
      CONCLUSION: These data show that a pulsatile venous flow pattern is a significant
      predictor of failure following RFS for IPVs.

PMID- 19576717
TI  - Carotid angioplasty and stenting: treatment of postcarotid endarterectomy
      restenosis is at least as safe as primary stenosis treatment.
AB  - OBJECTIVES: This study compared transcranial Doppler (TCD) imaging and outcomes
      of carotid angioplasty and stenting (CAS) in stenosis after carotid
      endarterectomy (CEA) vs primary atherosclerotic stenoses. METHODS: A
      prospectively accumulated database of 812 CAS procedures was analyzed
      retrospectively. Two groups were created. Group 1 had 72 restenoses at a mean of
      71 months (range, 5-245 months) after initial CEA. Group 2 had 740 primary
      stenoses. Clinical end points were cerebral ischemic events and death. TCD end
      points were numbers of isolated microemboli and microembolic showers during five
      procedural phases. RESULTS: Groups 1 and 2 were evenly matched for demographic
      data: median age, 70 vs 71 years; 44 (61%) vs 525 men (71%); 14 (19%) vs 147
      symptomatic (20%). Seven (0.9%) deaths and 10 major (1.2%) and 21 minor (2.6%)
      strokes occurred in group 2 (P = .049). Mean (standard deviation) numbers of
      isolated microemboli for groups 1 vs 2 were wiring, 37.0 (31.1) vs 50.4 (52.6);
      predilation, 14.8 (18.7) vs 21.7 (21.8); stent placement, 58.6 (31.1) vs 64.7
      (38.8); postdilation, 20.4 (16.5) vs 27.2 (34.9), cerebral protection device
      (CPD) use, 44.2 (30.2) vs 37.5 (36.8); total, 134.8 (68.7) vs 175.3 (113.8).
      Microembolic showers: wiring, 1.7 (4.5) vs 2.2 (6.4); predilation, 2.1 (4.1) vs
      3.3 (5.8); stent placement, 21.5 (22.0) vs 26.9 (25.1); postdilation, 5.3 (15.7)
      vs 5.0 (8.1); CPD use, 5.8 (6.9) vs 6.2 (8.9); total, 30.4 (36.0) vs 39.6 (35.0).
      TCD data for CPD use vs without for isolated emboli: wiring, 53.2 (45.1) vs 44.3
      (51.7); predilation, 24.7 (20.2) vs 18.2 (22.5); stent placement, 77.5 (34.8) vs
      53.5 (37.3); postdilation, 33.6 (36.6) vs 20.7 (21.8); CPD use, 38.3 (36.6) vs 0;
      total, 222.5 (113.8) vs 132.3 (89.1). Showers: wiring, 2.4 (6.6) vs 1.9 (5.8);
      predilation, 4.2 (6.4) vs 2.4 (5.0); stent placement, 38.9 (25.8) vs 16.2 (18.7);
      post-dilation, 7.0 (11.2) vs 3.4 (6.4); CPD use, 6.3 (8.9) vs 0; total, 58.4
      (37.7) vs 23.3 (23.1). P = .01 for showers during wiring and P < .001 for all
      other variables. After correction for the difference in CPD use between groups 1
      and 2 (17 out of 72 [24%] vs 369 out of 740 [50%]), no statistically significant
      differences remained in numbers of isolated emboli and embolic showers in the
      procedural phases or for the entire procedure. No statistically significant
      differences were found when TCD-detected microembolic load for early (<3 years
      between CEA and CAS) and late (>5 years) restenoses were compared. CONCLUSIONS:
      CAS for restenosis after CEA has a complication rate lower than primary CAS. The
      time interval between CEA and CAS did not influence micro embolic load.

PMID- 19576718
TI  - Idiopathic aneurysm of the common iliac artery in an 11-year-old child.
AB  - Arterial aneurysms are very rare in children, and aneurysms with an idiopathic
      etiology have been reported in only a few cases. In most cases, aneurysms are
      caused by infection, arteritides, collagen vascular disease, vascular
      malformations, or trauma. We report the case of an 11-year-old girl with an
      idiopathic and symptomatic left common iliac artery aneurysm. The aneurysm was
      resected and replaced by a reversed femoral vein. Because the external iliac
      artery was atrophied, an additional bypass with a reversed great saphenous vein
      was made. In the postoperative work-up, no etiologic cause could be found for the
      development of the aneurysm. The symptoms immediately subsided after the
      operation.

PMID- 19576719
TI  - Early and long-term outcomes of carotid endarterectomy in the very elderly: an 18
      year single-center study.
AB  - OBJECTIVE: To evaluate the perioperative (30-day) and long-term outcomes of
      carotid endarterectomy (CEA) in elderly patients with severe symptomatic and
      asymptomatic carotid disease. Although the efficacy of CEA in preventing stroke
      in selected patients has been clearly demonstrated, concern has been expressed
      about the role of CEA in people over 80 years old. METHODS: An analysis was
      conducted on a prospectively compiled computerized database of all primary CEAs
      performed at our institution from 1990 to 2007. Descriptive demographic data,
      risk factors, surgical details, perioperative strokes and deaths, and other
      complications were recorded. All patients underwent postoperative duplex
      ultrasound scanning and clinical follow-up at one, six, and 12 months, and yearly
      thereafter. Survival analyses were performed using Kaplan-Meier life-tables. Long
      term relative survival after CEA was assessed against age- and gender-matched
      controls. RESULTS: In all, 1769 CEAs were performed in 1562 patients, 193 of them
      (207 CEAs; group I) were > or = 80 years old and 1371 were younger (1562 CEAs;
      group II). All CEA procedures were performed with patients under deep general
      anesthesia with continuous perioperative EEG monitoring for selective shunting.
      No strokes or deaths occurred in group I, whereas there were 11 perioperative
      strokes and three deaths in group II (1%). A complete follow-up (median, 5.2
      years) was obtained in 185 elderly patients: no late occlusions or restenoses
      were detected, while the seven-year freedom from stroke and death were 96.6% and
      52.4%, respectively. The relative seven-year survival rate was 99.8%.
      CONCLUSIONS: CEA in elderly patients proved safe and effective, with an excellent
      long-term durability. The long-term relative survival after CEA in elderly
      patients was better than in an age-and gender-matched population, so the
      likelihood of living long enough to benefit from CEA is not jeopardized by being
      very elderly.

PMID- 19576720
TI  - Hybrid endovascular treatment of aneurysm degeneration in a rare right-aortic
      arch anomaly with Kommerell diverticulum.
AB  - We present a hybrid endovascular approach to a 6.5-cm aneurysm of the right-sided
      aortic arch with an aberrant left subclavian artery arising from a Kommerell
      diverticulum, connected to the left pulmonary artery through the ligamentum
      arteriosum. The two-step procedure consisted of a bilateral carotid-subclavian
      bypass, followed by an ascending aorta-bicarotid bypass and completed by an
      endovascular exclusion of the aneurysms by covering the whole aortic arch and its
      branches. The patient had no complications and is asymptomatic 21 months after
      surgery. Hybrid procedures may be helpful in complex aortic arch pathologies,
      reducing complications of challenging open surgery.

PMID- 19576721
TI  - Endotension after endovascular treatment of abdominal aortic aneurysm:
      percutaneous treatment.
AB  - Endotension is one of the possible specific late complications of endovascular
      treatment of abdominal aortic aneurysm (AAA). We describe the treatment of
      endotension in a small group of 3 patients (all men, aged 58, 70, and 70-years
      old) by translumbar puncture of the aneurysm sac and aspiration of its content.
      It was transudate and its culture was negative. Sac size reduced after aspiration
      in all patients and no subsequent enlargement was seen. Percutaneous translumbar
      puncture of the aneurysm sac with aspiration of sac content could be an easy and
      effective method of treatment in endotension. But a larger group of patients and
      long-term follow-up are needed.

PMID- 19576722
TI  - Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally
      advanced head pancreatic adenocarcinoma.
AB  - BACKGROUND: The most accepted treatment for locally advanced pancreatic
      adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the
      benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated
      by neoadjuvant CRT. METHODS: From January 1996 to December 2006, 64 patients with
      LAPA (borderline, n=49; unresectable, n=15) received 5-fluorouracil-cisplatin
      based CRT. Of the 64 patients, 47 had progressive disease at restaging.
      Laparotomy was performed for 17 patients, and PD was performed in 9 patients
      (resected group). Fifty-five patients had CRT followed by gemcitabine-based
      chemotherapy (unresected group). RESULTS: The median survival and overall 5 years
      survival duration of all 64 patients were 14 months and 12%, respectively. The
      mean delay between diagnosis and surgical resection was 5.5 months. Mortality and
      morbidity from PD were 0% and 33%, respectively. The median survival of the
      resected group vs. the unresected group was 24 months vs. 13 months. Three
      specimens presented a major pathological response at histological examination. No
      involved margins were found and positive lymph nodes were found in one patient.
      Resected patients developed distant metastases. CONCLUSIONS: PD after CRT was
      safe and resected patients had interesting survival rates. However, resected
      patients developed metastatic disease and new neoadjuvant regimens are needed to
      improve the survival of these patients.

PMID- 19576723
TI  - Improving lymph node detection in colon cancer in community hospitals and their
      pathology department in southern Netherlands.
AB  - AIM: The aim was to investigate whether a set of measures directed at increasing
      lymph node (LN) detection among colon cancer patients led to clinically relevant
      changes in LN detection rate. METHODS: Data of all patients with curative colon
      cancer (pT(any) N(any) M0) diagnosed in 1999-2007 whose resection specimens were
      evaluated by the Institute for Pathology and Medical Microbiology in Eindhoven
      (n=1501) were included. Feedback to specialists, increased fixation time, and ex
      vivo injection of the specimen with Patent blue V dye were used to increase LN
      detection rate. Trends in the proportion of patients with insufficient LNs
      examined were investigated; moreover, the Patent blue-stained patients (n=86)
      were compared with a group of unstained patients (n=84). Based on the decrease in
      the proportion of high-risk node-negative patients, a calculation of chemotherapy
      related costs saved was made. RESULTS: The proportion of patients with <12 LNs
      examined decreased from 87% in 1999 to 48% in 2007 (p(trend)<0.0001). In the
      stained group this was 37%, versus 56% for the unstained group (p=0.010). In
      1999, 79% of stage II patients were high-risk compared to 55% in 2007, which
      translates to a saving of almost 1,000,000 euro based on 92 stage II patients
      diagnosed in 2007. CONCLUSION: A diverse set of measures increased the number of
      examined lymph nodes among patients with colon cancer. Large savings can be made
      due to the reduced proportion of high-risk node-negative patients who would
      otherwise have received adjuvant chemotherapy.

PMID- 19576724
TI  - [Medical paediatric simulation: a European survey].
AB  - OBJECTIVE: To present the effective applications of paediatric medical simulation
      in terms of education, evaluation, density, development, goals and constraints.
      STUDY DESIGN: Survey realized within 38 paediatric simulation centres (PSC) in
      Europe, identified by Web search and through the Society in Europe for Simulation
      Applied to Medicine (SESAM. RESULTS: Twenty centers answered the questionnaire
      (52%). Ninety-four percent of the PSC had beforehand acquired an experience of
      adult medical simulation, 94.6% of the PSC were created before 2006. Ninety
      percent of the PSC owned at least one high-fidelity pediatric simulator. The 80%
      of the PSC indicated multiple funding sources. Eighty percent of the PSC had at
      least one specific instructor for the paediatric simulation (average=2.7
      paediatric instructors per centre). The PCS reported to get onto various topics:
      neonatology (25% of the PCS), prehospital medicine (36.8%), paediatric
      anaesthesiology (74%) and paediatric intensive care (89%). Simulation allowed 70%
      of the centers to lead some research project. Ninety-five percent of the centers
      agreed about an European collaboration on research projects or about the
      mutualization of the created scenarios. CONCLUSION: The material, financial and
      human means of the interviewed centres are consequential but heterogeneous in
      Europe. MSP offers numerous and various application fields and generates some
      research activity.

PMID- 19576725
TI  - [Introduction of a bar coding pharmacy stock replenishment system in a
      prehospital emergency medical unit: economical impact].
AB  - OBJECTIVE: To assess economical impact after introduction of a bar coding
      pharmacy stock replenishment system in a prehospital emergency medical unit.
      STUDY DESIGN: Observational before and after study. METHODS: A computer system
      using specific software and bare-code technology was introduced in the pre
      hospital emergency medical unit (Smur). Overall activity and costs related to
      pharmacy were recorded annually during two periods: the first 2 years period
      before computer system introduction and the second one during the 4 years
      following this system installation. RESULTS: The overall clinical activity
      increased by 10% between the two periods whereas pharmacy related costs
      continuously decreased after the start of pharmacy management computer system
      use. Pharmacy stock management was easier after introduction of the new stock
      replenishment system. The mean pharmacy related cost of one patient management
      was 13 Euros before and 9 Euros after the introduction of the system. The overall
      cost savings during the studied period was calculated to reach 134,000 Euros.
      CONCLUSION: The introduction of a specific pharmacy management computer system
      allowed to do important costs savings in a prehospital emergency medical unit.

PMID- 19576726
TI  - [Human longevity: 150 years and more?].

PMID- 19576727
TI  - Implant durability and knee function after total knee arthroplasty in the
      morbidly obese patient.
AB  - This study investigated the effect of body mass index (BMI) on outcomes after
      cemented tricompartmental total knee arthroplasty (TKA). Functional and
      radiographic Knee Society scores in 71 patients (94 knees) with BMI 30 to 39 and
      31 patients (41 knees) with BMI > or =40 were compared with 67 patients (85
      knees) with BMI 20 to 29 at a mean follow-up of 5.4 years. Total knee
      arthroplasty rates of success (79%), complication (17%), and revision (6%) were
      independent of BMI. The BMI > or =40 group, however, was 5.4x (95% confidence
      interval, 2.1-14.7) more likely to develop patellar radiolucencies, had poorer
      hamstring and quadriceps conditioning, and had more patellofemoral symptoms.
      Forty percent of TKAs at BMI > or =40 with patellar radiolucencies failed. In
      conclusion, TKA benefits were realized at all BMI, but at BMI > or =40, more
      rehabilitation and monitoring are recommended.

PMID- 19576728
TI  - Human dermal fibroblasts: a potential cell source for endothelialization of
      vascular grafts.
AB  - BACKGROUND: Recently, there has been an intense ongoing search for suitable cell
      sources for vascular tissue engineering. Previous studies report that cells with
      multilineage potential have been found within the connective stroma of the skin.
      In line with this, preliminary data from our group suggest that human dermal
      fibroblasts have the capacity to alter their phenotype into an endothelial cell
      like phenotype in vitro. As a first step in using these cells in vascular tissue
      engineering, we investigated their ability to form an endothelial cell-like layer
      on a scaffold in vitro. Furthermore, we studied the possibility of seeding dermal
      fibroblasts on a scaffold and later commencing with induction toward an
      endothelial cell-like phenotype. METHODS: Cells cultured in either normal
      fibroblast medium or endothelial induction medium were seeded on a gelatin-based
      scaffold. To study the organization of cells, routine staining was performed.
      Differentiation was confirmed by Western blotting and immunohistochemistry with
      antibodies directed toward molecules commonly used to identify endothelial cells.
      RESULTS AND CONCLUSION: Our data support that human dermal fibroblasts
      differentiated toward endothelial cell-like cells prior to seeding showed
      histological resemblance to mature endothelial cells, while fibroblasts seeded
      and later induced into endothelial differentiation grew in multilayer. However,
      expression of various surface molecules indicative of an endothelial phenotype
      was seen using both techniques. In conclusion, the results presented in this
      study indicate that human dermal fibroblasts differentiated toward an endothelial
      cell-like phenotype may be a novel cell source for endothelialization of vascular
      grafts.

PMID- 19576729
TI  - Decreased VEGF mRNA expression in the dorsolateral prefrontal cortex of
      schizophrenia subjects.

PMID- 19576730
TI  - Circulating levels of adiponectin, oxidized LDL and C-reactive protein in
      Portuguese patients with psoriasis vulgaris, according to body mass index,
      severity and duration of the disease.

PMID- 19576731
TI  - Altered expression and modulation of activity-regulated cytoskeletal associated
      protein (Arc) in serotonin transporter knockout rats.
AB  - A gene variant in the human serotonin transporter (SERT) can increase the
      vulnerability to mood disorders. SERT knockout animals show similarities to the
      human condition and represent an important tool to investigate the mechanisms
      underlying the pathologic condition in humans. Along this line of thinking, we
      used SERT KO rats (SERT(+/-) and SERT(-/-)) to investigate abnormalities in the
      expression and function of the activity-regulated gene Arc (Activity-regulated
      cytoskeletal associated protein) and the early inducible gene Zif-268, (zinc
      finger binding protein clone 268), which are important players in neuronal
      plasticity. We found lower basal Arc mRNA levels in hippocampus and prefrontal
      cortex of mutant rats in comparison with wild-type animals. Moreover SERT mutant
      rats show altered stress responsiveness. Indeed an acute swim stress
      significantly up-regulated the levels of Arc mRNA in hippocampus and prefrontal
      cortex, as well as of Zif-268 in frontal cortex, only in SERT(+/-) and SERT(-/-)
      rats. These alterations may be associated to behavioral traits linked to SERT and
      may contribute to the neuroplastic and morphological changes observed in
      depression.

PMID- 19576732
TI  - A nuclear magnetic resonance study of the phase transitions and electric
      quadrupole Raman processes of M5H3(SO4)4xH2O (M=Na, K, Rb, and Cs) single
      crystals.
AB  - The spin-lattice relaxation times and spin-spin relaxation times for (1)H and M
      in M(5)H(3)(SO(4))(4)xH(2)O (M=Na, K, Rb, and Cs) single crystals grown using the
      slow-evaporation method were measured as functions of temperature. Two kinds of
      protons were identified in the M(5)H(3)(SO(4))(4)xH(2)O structure: acid protons
      and water protons. Our experimental results show that the acid and water protons
      in Cs(5)H(3)(SO(4))(4)xH(2)O are involved in phase transitions of this crystal,
      whereas neither type of proton is involved in the phase transitions of the other
      three crystal type (M(5)H(3)(SO(4))(4)xH(2)O; M=Na, K, and Rb). Moreover, the
      relaxation times for the M (=Na, K, and Rb) nuclei in these crystals were found
      to decrease with increasing temperature and can be described with T(1)(-1)
      proportional, variantT(k) (k=2). The T(1) results for M (=Na, K, and Rb) in
      M(5)H(3)(SO(4))(4)xH(2)O crystals can be explained in terms of a relaxation
      mechanism in which the lattice vibrations are coupled to the nuclear electric
      quadrupole moments.

PMID- 19576733
TI  - Cinnamon zeylanicum bark extract and powder mediated green synthesis of nano
      crystalline silver particles and its bactericidal activity.
AB  - The exploitation of various plant materials for the biosynthesis of nanoparticles
      is considered a green technology as it does not involve any harmful chemicals.
      The present study reports the synthesis of silver (Ag) nanoparticles from silver
      precursor using the bark extract and powder of novel Cinnamon zeylanicum. Water
      soluble organics present in the plant materials were mainly responsible for the
      reduction of silver ions to nano-sized Ag particles. TEM and XRD results
      confirmed the presence of nano-crystalline Ag particles. The pH played a major
      role in size control of the particles. Bark extract produced more Ag
      nanoparticles than the powder did, which was attributed to the large availability
      of the reducing agents in the extract. Zeta potential studies showed that the
      surface charge of the formed nanoparticles was highly negative. The EC(50) value
      of the synthesized nanoparticles against Escherichia coli BL-21 strain was 11+/
      1.72 mg/L. Thus C. zeylanicum bark extract and powder are a good bio
      resource/biomaterial for the synthesis of Ag nanoparticles with antimicrobial
      activity.

PMID- 19576734
TI  - Effect of protein solution components in the adsorption of Herbaspirillum
      seropedicae GlnB protein on mica.
AB  - The adsorption of proteins and its buffer solution on mica surfaces was
      investigated by atomic force microscopy (AFM). Different salt concentration of
      the Herbaspirillum seropedicae GlnB protein (GlnB-Hs) solution deposited on mica
      was investigated. This protein is a globular, soluble homotrimer (36kDa), member
      of PII-like proteins family involved in signal transducing in prokaryote.
      Supramolecular structures were formed when this protein was deposited onto bare
      mica surface. The topographic AFM images of the GlnB-Hs films showed that at high
      salt concentration the supramolecular structures are spherical-like, instead of
      the typical doughnut-like shape for low salt concentration. AFM images of NaCl
      and Tris from the buffer solution showed structures with the same pattern as
      those observed for high salt protein solution, misleading the image
      interpretation. XPS experiments showed that GlnB protein film covers the mica
      surface without chemical reaction.

PMID- 19576735
TI  - A correlation between the virulence and the adhesion of Listeria monocytogenes to
      silicon nitride: an atomic force microscopy study.
AB  - Listeria monocytogenes is a facultative intracellular Gram-positive bacterium
      that is widely distributed in the environment. Despite being pathogenic at the
      species level, L. monocytogenes in fact comprises a diversity of strains from
      pathogenic ones that can result in disease and/or mortality to others that are
      relatively avirulent. The main goal of the current study was to answer the
      question on whether enhanced binding or attachment of L. monocytogenes to inert
      surfaces bears any relationship to pathogenicity in food-borne isolates. To
      answer this question, the nanoscale adhesion forces of eight L. monocytogenes
      strains that vary in their pathogenicity levels to a model surface of silicon
      nitride were quantified using atomic force microscopy. The strains used were the
      highly pathogenic (EGDe, 874, 1002, ATCC 19115), the intermediate pathogenic
      (ATCC 19112, ATCC 19118), and the non pathogenic (ATCC 15313 and HCC25). Our
      results indicate that the average nanoscale adhesion (in nN) and the 50% lethal
      dose (LD50) of strain virulence quantified in mice are logarithmically correlated
      according to: (nN)=-0.032ln(LD50)+1.040, r(2)=0.96. Such correlation indicates
      that nanoscale adhesion could potentially be used as a design criterion to
      distinguish between virulent and avirulent L. monocytogenes strains. Finally,
      stronger adhesion of virulent strains to inert surfaces modeled by silicon
      nitride might be a way for pathogenic strains to survive better in the
      environment and thus increase their likelihood of infecting animals or humans.

PMID- 19576736
TI  - Formation of individual protein channels in lipid bilayers suspended in
      nanopores.
AB  - Free-standing lipid bilayers are formed in regularly arranged nanopores of 200,
      400 and 800 nm in a 300 nm thin hydrophobic silicon nitride membrane separating
      two fluid compartments. The extraordinary stability of the lipid bilayers allows
      us to monitor channel formation of the model peptide melittin and alpha-hemolysin
      from Staphylococcus aureus using electrochemical impedance spectroscopy and
      chronoamperometry. We observed that melittin channel formation is voltage
      dependent and transient, whereas transmembrane heptameric alpha-hemolysin
      channels in nano-BLMs persist for hours. The onset of alpha-hemolysin-mediated
      conduction depends on the applied protein concentration and strongly on the
      diameter of the nanopores. Heptameric channel formation from adsorbed alpha
      hemolysin monomers needs more time in bilayers suspended in 200 nm pores compared
      to bilayers in pores of 400 and 800 nm diameters. Diffusion of sodium ions across
      alpha-hemolysin channels present in a sufficiently high number in the bilayers
      was quantitatively and specifically determined using ion selective electrodes.
      The results demonstrate that relatively small variations of nano-dimensions have
      a tremendous effect on observable dynamic biomolecular processes. Such nanopore
      chips are potentially useful as supports for stable lipid bilayers to establish
      functional assays of membrane proteins needed in basic research and drug
      discovery.

PMID- 19576737
TI  - A monolayer study on phase behavior and morphology of binary mixtures of
      sulfatides with DPPC and DPPE.
AB  - Sulfatides are important constituents of brain myelin membranes and it is thought
      to be involved in lateral domain formation in biological membranes. In this work,
      the interaction of mixed systems of sulfatide with 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) and 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine
      (DPPE), two of the major components in biological membranes, was investigated
      using the monolayer technique at the air-water interface. Based on the regular
      solution theory, the miscibility of the two binary systems in the mixed monolayer
      was evaluated in terms of mean surface area per molecule (A(m)), excess molecular
      area (DeltaA((ex))), surface excess Gibbs energy (DeltaG((ex))), interaction
      parameter (omega) as well as activity coefficients (f(1) and f(2)) of formed
      films. Thermodynamic analysis indicates in the two binary systems with negative
      deviations from the ideal behavior. Accordingly, the values of the Gibbs energy
      of mixing, sulfatide-DPPC form stable mixtures at X(sul)=0.4 (X(sul) is molar
      ratio of sulfatide in binary mixture) for all the selected pressures. As for
      sulfatide/DPPE system, at pi=5 and 30 mN m(-1), the minimum for the Gibbs energy
      of mixing was found at X(sul)=0.6 and 0.2 respectively. But the minimum appeared
      at X(sul)=0.4 for other surface pressures. The activity coefficients (f(1) and
      f(2)) of mixed monolayers were evaluated which show a marked dependence on the
      mole faction of sulfatide X(sul). AFM images could support the above findings as
      well as interpretation.

PMID- 19576738
TI  - Antibacterial effect of essential oils from two medicinal plants against
      Methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Antimicrobial properties of plants essential oils (EOs) have been investigated
      through several observations and clinical studies which purpose them as potential
      tools to overcome the microbial drug resistance problem. The aim of this research
      is to study the antibacterial effect of two traditional plants essential oils,
      Thymus vulgaris and Eucalyptus globulus against clinical isolates of Methicillin
      resistant Staphylococcus aureus (MRSA) and other standard bacterial strains
      through disk diffusion and agar dilution methods. Gas Chromatography (GC) and Gas
      Chromatography/Mass Spectrometry (GC/MS) analysis examined the chemical
      composition of the oils. Results revealed both of oils to possess degrees of
      antibacterial activity against Gram (+) and Gram (-) bacteria. T. vulgaris EO
      showed better inhibitory effects than E. globulus essential oil. GC analysis of
      T. vulgaris resulted in thymol as the oil major compound whereas GC/MS assay
      exhibited eucalyptol as the most abundant constitute of E. globulus EO. These
      results support previous studies on these oils and suggest an additional option
      to treat MRSA infections. Clinical and further analytical trials of these data
      are necessary to confirm the obtained outcomes.

PMID- 19576739
TI  - Monoamine levels in rat striatum after acute intraperitoneal injection of
      strictosidinic acid isolated from Psychotria myriantha Mull. Arg. (Rubiaceae).
AB  - Strictosidinic acid 10mg/kg, isolated from Psychotria myriantha leaves, were
      administered intraperitoneally to Wistar male rats (n=5-6). After 60 minutes,
      striatum was dissected, homogenized and injected onto HPLC-ED chromatographic
      system. It was observed a 28.7% reduction in the 5-HT levels followed up by an
      increase of 5-HIAA levels (29.4%). Furthermore there was a decrease of 8.0% in DA
      levels and an increase in the levels of metabolites DOPAC (21.5%) and HVA
      (52.5%). The results indicate that strictosidinic acid has a promising effect in
      the central nervous system, justifying more studies about the central actions of
      Psychotria compounds.

PMID- 19576740
TI  - Acetylcholinesterase enzyme inhibitory potential of standardized extract of
      Trigonella foenum graecum L and its constituents.
AB  - Ethno pharmacological approach has provided several leads to identify potential
      new drugs from plant sources, including those for memory disorders.
      Acetylcholinesterase inhibitors (AChEI) give a symptomatic relief to some of the
      clinical manifestations of the disease. The main objective of this study is to
      standardize the extract of Trigonella foenum graecum L with trigonelline by HPTLC
      method and determine the in vitro AChE inhibitory activity of Trigonella foenum
      graecum L and its constituents using galanthamine as a reference. Different
      concentrations of hydro alcoholic extract of Trigonella foenum graecum and
      trigonelline were subjected to HPTLC analysis using the mobile phase n propanol,
      methanol and water (4:1:2, v/v). The R(f) of trigonelline was found to be 0.43,
      and the correlation coefficient of 0.99 was indicative of good linear dependence
      of peak area on concentration. The concentration of trigonelline was found to be
      13mgg(-1)w/w in the hydro alcoholic extract of Trigonella foenum graecum. The
      AChE inhibitory activity of crude fenugreek seed extracts, fractions and
      trigonelline was evaluated using Ellman's method in 96-well micro plate's assay
      and TLC bioassay detection. The ethyl acetate fraction of the alcohol extract
      (IC50 53.00 +/- 17.33microg/ml), and total alkaloid fraction (IC50 9.23+/
      6.08microg/ml) showed potential AChE inhibition. Trigonelline showed IC50 233+/
      0.12microM. Galanthamine was used as standard and it showed inhibition of acetyl
      cholinesterase with an IC50 value of 1.27+/-0.21microM.

PMID- 19576742
TI  - Immunomodulatory, analgesic and antipyretic effects of violacein isolated from
      Chromobacterium violaceum.
AB  - Violacein was isolated from Chromobacterium violaceum, a soil Gram negative
      bacterium collected from the forest water body soil sample of Kolli Hills; Tamil
      Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic
      activities of violacein were investigated in wistar rats and mice. Analgesic
      effect was evaluated by acetic acid- induced writhing, formalin induced paw
      licking and hotplate tests. Immunomodulatory effect was investigated by using
      ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)
      induced DTH tests. Antipyretic activity was evaluated by yeast- induced
      hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin.
      Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that
      violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells.
      Violacein also produced significant (p<0.05) analgesic activity in acetic acid
      induced writhing response, formalin induced paw licking response and hot plate
      analysis. Treatment with violacein showed a significant (p<0.05) dose-dependent
      reduction in pyrexia in rats. The results suggest that violacein possesses potent
      immunomodulatory, analgesic and antipyretic activities.

PMID- 19576741
TI  - Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona
      squamosa L. bark.
AB  - Caryophyllene oxide was isolated from an unsaponified petroleum ether extract of
      the bark of Annona squamosa and studied for its analgesic and anti-inflammatory
      activity. Caryophyllene oxide at the doses of 12.5 and 25mg/kg body wt. and
      unsaponified petroleum ether extract at a dose of 50mg/kg body wt. showed
      significant central as well as peripheral analgesic, along with anti
      inflammatory, activity. These activities of caryophyllene oxide were comparable
      with the standard drug used in the respective experiments.

PMID- 19576743
TI  - In vitro anti-leukemic activity of the ethno-pharmacological plant Scutellaria
      orientalis ssp. carica endemic to western Turkey.
AB  - AIM OF THIS STUDY: Within the genus Scutellaria various species are used in
      different folk medicines throughout Asia. Traditional Chinese Medicine (TCM) uses
      S. baicalensis (Labiatae) to treat various inflammatory conditions. The root
      shows strong anticancer properties in vitro and was suggested for clinical trials
      against multiple myeloma. Further, S. barbata was successfully tested against
      metastatic breast cancer in a phase I/II trial. Therefore, we investigated the
      anti-cancer properties of S. orientalis L. ssp. carica Edmondson, an endemic
      subspecies from the traditional medicinal plant S. orientalis L. in Turkey, which
      is used to promote wound healing and to stop haemorrhage. MATERIALS AND METHODS:
      Freeze-dried plant material was extracted with petroleum ether, dichloromethane,
      ethyl acetate, and methanol and the bioactivity of these extracts was analysed by
      proliferation assay, cell death determination, and by investigating protein
      expression profiles specific for cell cycle arrest and apoptosis. RESULTS: The
      strongest anti-leukemic activity was shown by the methanol extract, which
      contained apigenin, baicalein, chrysin, luteolin and wogonin, with an IpC50 of 43
      microg/ml (corresponding to 1.3mg/ml of dried plant material) which correlated
      with cyclin D1- and Cdc25A suppression and p21 induction. At 132 microg/ml (=4
      mg/ml of the drug) this extract caused genotoxic stress indicated by substantial
      phosphorylation of the core histone H2AX (gamma-H2AX) followed by activation of
      caspase 3 and signature-type cleavage of PARP resulting in a 55% apoptosis rate
      after 48 hours of treatment. CONCLUSIONS: Here, we report for the first time that
      S. orientalis L. ssp. carica Edmondson exhibited potent anti-leukaemic properties
      likely through the anti-proliferative effect of baicalein and the genotoxic
      property of wogonin.

PMID- 19576744
TI  - Chemical study, antimalarial and antioxidant activities, and cytotoxicity to
      human breast cancer cells (MCF7) of Argania spinosa.
AB  - INTRODUCTION: In our work, we evaluate the potential antioxidant, antimalarial
      activity and also activity against human breast cancer cells (MCF7) of Argan
      fruit extracts using in vitro models to validate the traditional use of this
      plant. Its chemical composition was also studied to begin the understanding of
      its activities, waiting to find the structure-activity relationship. RESULTS:
      Polyphenols (89.4-218.5 eqGallic acid (mg/g dry)), tannins (39.3-214.0 eqCatechin
      (mg/g dry)), flavonoids (3.4-11.1 eqQuercetin (mg/g dry)) and anthocyanins (0.74
      10.92 eqCyanindin (mug/g dry)) were quantified. A good (ethyl acetate and
      decoction) and moderate (petroleum ether) antioxidant activity were obtained for
      DPPH (IC(50) 32.3-600.8 microg/ml) and ABTS (IC(50) 11.9-988.8 microg/ml) assays.
      In addition, we found a good antimalarial activity (IC(50) 35 to >100 microg/ml)
      and human breast cancer cells activity (IC(50) 42 to >100 microg/ml).
      CONCLUSIONS: The ethyl acetate extract and the decoction show interesting
      antimalarial and antioxidant activities. The results indicate a good correlations
      between anthocyanins quantitiy and the potential antioxidant (R(2)=0.9867) and
      also to antimalarial activity (R(2)=0.8175).

PMID- 19576745
TI  - Nontuberculous mycobacteria isolated during the treatment of pulmonary
      tuberculosis.
AB  - BACKGROUND: The significance of nontuberculous mycobacteria (NTM) isolated from a
      patient during therapy for pulmonary tuberculosis (TB) is uncertain. We
      investigated the frequency and clinical significance of NTM isolated from
      patients receiving anti-TB treatment. METHODS: We conducted a retrospective
      cohort study of all patients with culture-confirmed pulmonary TB, and identified
      patients with respiratory cultures positive for NTM during therapy for pulmonary
      TB. RESULTS: From January 2003 to December 2005, 958 patients were diagnosed with
      culture-confirmed pulmonary TB. NTM were isolated from 113 specimens in 68 (7.1%)
      patients during anti-TB treatment. The most frequently isolated NTM species were
      Mycobacterium abscessus (n=35, 31%), Mycobacterium fortuitum (n=17, 15%),
      Mycobacterium avium complex (n=9, 8%), and Mycobacterium gordonae (n=9, 8%).
      Forty-eight (71%) patients had only one positive culture, while 20 (29%) had two
      or more positive cultures for NTM. Only two (3%) patients who had two or more
      positive culture after anti-TB treatment showed the same NTM species, which were
      M. abscessus. CONCLUSION: The isolation of NTM in patients with pulmonary TB is
      not uncommon during anti-TB treatment. However, this is likely the result of
      colonization, a transient infection, or specimen contamination. The co-existence
      of pulmonary TB and NTM lung disease may be rare but should be considered in
      patients with relatively virulent NTM species such as M. abscessus.

PMID- 19576746
TI  - Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction
      intercellular communication by blocking phosphorylation of connexin 43 via the
      MEK/ERK signaling pathway.
AB  - Cocoa, a good source of dietary antioxidative polyphenols, exhibited
      anticarcinogenic activity in animal models, but the molecular mechanisms of the
      chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction
      intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa
      polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide
      (H(2)O(2))-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE
      inhibited the H(2)O(2)-induced phosphorylation and internalization of connexin
      43, which is a regulating protein of GJIC in RLE cells. The H(2)O(2)-induced
      accumulation of reactive oxygen species and activation of extracellular signal
      regulated kinase were inhibited by CPE treatment. However, CPE did not block
      H(2)O(2)-induced phosphorylation of p38 mitogen-activated protein kinase. An ex
      vivo kinase assay demonstrated that CPE inhibited the H(2)O(2)-induced mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1
      activity in RLE cell lysates. Ex vivo pull-down assay data revealed that CPE
      directly bound with MEK1 to inhibit MEK1 activity. These results indicate that
      CPE protects against the H(2)O(2)-induced inhibition of GJIC through antioxidant
      activity and direct inhibition of MEK activity, which may contribute to its
      chemopreventive potential.

PMID- 19576747
TI  - Gene expression profiling of 3T3-L1 adipocytes exposed to phloretin.
AB  - Adipocyte dysfunction plays a major role in the outcome of obesity, insulin
      resistance and related cardiovascular complications. Thus, considerable efforts
      are underway in the pharmaceutical industry to find molecules that target the now
      well-documented pleiotropic functions of adipocyte. We previously reported that
      the dietary flavonoid phloretin enhances 3T3-L1 adipocyte differentiation and
      adiponectin expression at least in part through PPAR gamma activation. The
      present study was designed to further characterize the molecular mechanisms
      underlying the phloretin-mediated effects on 3T3-L1 adipocytes using microarray
      technology. We show that phloretin positively regulates the expression of
      numerous genes involved in lipogenesis and triglyceride storage, including GLUT4,
      ACSL1, PEPCK1, lipin-1 and perilipin (more than twofold). The expression of
      several genes encoding adipokines, in addition to adiponectin and its receptor,
      is positively or negatively regulated in a way that suggests a possible reduction
      in systemic insulin resistance and obesity-associated inflammation. Improvement
      of insulin sensitivity is also suggested by the overexpression of genes
      associated with insulin signal transduction, such as CAP, PDK1 and Akt2. Many of
      these genes are PPAR gamma targets, confirming the involvement of PPAR gamma
      pathway in the phloretin effects on adipocytes. In light of these microarray
      data, it is reasonable to assume that phloretin may be beneficial for reducing
      insulin resistance, in a similar way to the thiazolidinedione class of
      antidiabetic drugs.

PMID- 19576748
TI  - Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in
      3T3-L1 adipocytes.
AB  - Hydroxytyrosol (HT) in extra-virgin olive oil is considered one of the most
      important polyphenolic compounds responsible for the health benefits of the
      Mediterranean diet for lowering incidence of cardiovascular disease, the most
      common and most serious complication of diabetes. We propose that HT may prevent
      these diseases by a stimulation of mitochondrial biogenesis that leads to
      enhancement of mitochondrial function and cellular defense systems. In the
      present study, we investigated effects of HT that stimulate mitochondrial
      biogenesis and promote mitochondrial function in 3T3-L1 adipocytes. HT over the
      concentration range of 0.1-10 micromol/L stimulated the promoter transcriptional
      activation and protein expression of peroxisome proliferator-activated receptor
      (PPAR) coactivator 1 alpha (PPARGC1 alpha, the central factor for mitochondrial
      biogenesis) and its downstream targets; these included nuclear respiration
      factors 1 and 2 and mitochondrial transcription factor A, which leads to an
      increase in mitochondrial DNA (mtDNA) and in the number of mitochondria.
      Knockdown of Ppargc1 alpha by siRNA blocked HT's stimulating effect on Complex I
      expression and mtDNA copy number. The HT treatment resulted in an enhancement of
      mitochondrial function, including an increase in activity and protein expression
      of Mitochondrial Complexes I, II, III and V; increased oxygen consumption; and a
      decrease in free fatty acid contents in the adipocytes. The mechanistic study of
      the PPARGC1 alpha activation signaling pathway demonstrated that HT is an
      activator of 5'AMP-activated protein kinase and also up-regulates gene expression
      of PPAR alpha, CPT-1 and PPAR gamma. These data suggest that HT is able to
      promote mitochondrial function by stimulating mitochondrial biogenesis.

PMID- 19576749
TI  - Sulforaphane suppresses ultraviolet B-induced inflammation in HaCaT keratinocytes
      and HR-1 hairless mice.
AB  - Ultraviolet B (UVB) irradiation induces skin damage and inflammation. One way to
      reduce the inflammation is via the use of molecules termed photochemopreventive
      agents. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SF), which is found
      in cruciferous vegetables, is known for its potent physiological properties. This
      study was designed to evaluate the effect of SF on skin inflammation in vitro and
      in vivo. In in vitro study using immortalized human keratinocytes (HaCaT), UVB
      caused marked inflammatory responses [i.e., decrease of HaCaT viability and
      increase of production of an inflammatory marker interleukin-6 (IL-6)]. SF
      recovered the cell proliferation and suppressed the IL-6 production. These anti
      inflammatory effects of SF were explained by its ability to reduce UVB-induced
      inflammatory gene expressions [IL-6, IL-1beta and cyclooxgenase-2 (COX-2)].
      Because SF seems to have an impact on COX-2 expression, we focused on COX-2 and
      found that SF reduced UVB-induced COX-2 protein expression. In support of this,
      PGE(2) released from HaCaT was suppressed by SF. Western blot analysis revealed
      that SF inhibited p38, ERK and SAPK/JNK activation, indicating that the
      inhibition of mitogen-activated protein kinases (MAPK) by SF would attenuate the
      expression of inflammatory mediators (e.g., COX-2), thereby reducing inflammatory
      responses. Moreover, we conducted skin thickening assay using HR-1 hairless mice
      and found that UVB-induced skin thickness, COX-2 protein expression and
      hyperplasia were all suppressed by feeding SF to the mice. These results suggest
      that SF has a potential use as a compound for protection against UVB-induced skin
      inflammation.

PMID- 19576750
TI  - Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK,
      JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1
      expression in TNF-alpha- and IFN-gamma-stimulated C6 glioma cells.
AB  - In neurodegenerative disorders, activated glial cells overproduce nitric oxide
      (NO), which causes neurotoxicity. Inducible NO synthase (iNOS) is a potential
      therapeutic target in neurodegenerative diseases. Here, we examined the action of
      fucoidan, a high-molecular-weight sulfated polysaccharide, on tumor necrosis
      factor-alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced NO production
      in C6 glioma cells. Fucoidan suppressed TNF-alpha- and IFN-gamma-induced NO
      production and iNOS expression. In addition, fucoidan inhibited TNF-alpha- and
      IFN-gamma-induced AP-1, IRF-1, JAK/STAT and p38 mitogen-activated protein kinase
      (MAPK) activation and induced scavenger receptor B1 (SR-B1) expression. Blocking
      of SR-B1 did not reverse the inhibitory effect of fucoidan on TNF-alpha- and IFN
      gamma- stimulated NO production. However, inhibition of SR-B1 expression by siRNA
      increased iNOS expression and p38 phosphorylation in TNF-alpha- and IFN-gamma
      stimulated C6 cells. Overall, p38 MAPK, AP-1, JAK/STAT and IRF-1 play an
      important role in the inhibitory effect of fucoidan on TNF-alpha- and IFN-gamma
      stimulated NO production, and intracellular SR-B1 expression may be related to
      the inhibition of iNOS expression by fucoidan via regulation of p38
      phosphorylation. The present results also suggest that fucoidan could be a
      potential therapeutic agent for treating inflammatory-related neuronal injury in
      neurological disorders.

PMID- 19576751
TI  - Differential response to zinc-induced apoptosis in benign prostate hyperplasia
      and prostate cancer cells.
AB  - Zinc concentrations in the prostate are uniquely high but are dramatically
      decreased with prostate cancer. Studies have suggested that increasing zinc in
      the prostate may be a potential therapeutic strategy. The goal of this study was
      to evaluate the antiproliferative effects of zinc in prostate cancer cells (PC-3)
      and noncancerous benign prostate hyperplasia (BPH) cells (BPH-1) and to define
      possible mechanisms. PC-3 and BPH-1 cells were treated with zinc (0-250 microM)
      for 24 and 48 h, and cell growth and viability were examined. Apoptosis was
      assessed by phosphatidylserine externalization, caspase activation and protein
      expression of B-cell CLL/lymphoma 2 (Bcl-2)-associated X protein (BAX):Bcl-2. BPH
      1 cells were more sensitive to the antiproliferative effects of zinc compared to
      PC-3. The response to zinc in PC-3 and BPH-1 cells differed as evidenced by
      opposing effects on Bcl-2:BAX expression. Additionally, different effects on the
      nuclear expression and activity of the p65 subunit of nuclear factor kappa B were
      observed in response to zinc between the two cell types. The differential
      response to zinc in PC-3 and BPH-1 cells suggests that zinc may serve an
      important role in regulating cell growth and apoptosis in prostate cancer and
      hyperplasia cells.

PMID- 19576752
TI  - Phytase supplementation increases bone mineral density, lean body mass and
      voluntary physical activity in rats fed a low-zinc diet.
AB  - Phytic acid forms insoluble complexes with nutritionally essential minerals,
      including zinc (Zn). Animal studies show that addition of microbial phytase (P)
      to low-Zn diets improves Zn status and bone strength. The present study
      determined the effects of phytase supplementation on bone mineral density (BMD),
      body composition and voluntary running activity of male rats fed a high phytic
      acid, low-Zn diet. In a factorial design, rats were assigned to ZnLO (5 mg/kg
      diet), ZnLO+P (ZnLO diet with 1500 U phytase/kg) or ZnAD (30 mg/kg diet) groups
      and were divided into voluntary exercise (EX) or sedentary (SED) groups, for 9
      weeks. SED rats were significantly heavier from the second week, and no catch-up
      growth occurred in EX rats. Feed intakes were not different between groups
      throughout the study. ZnLO animals had decreased food efficiency ratios compared
      to both phytase-supplemented (ZnLO+P) and Zn-adequate (ZnAD) animals (P<.01
      compared to ZnLO). The ZnLO+P and ZnAD rats ran 56-75 km more total distance than
      ZnLO rats (P<.05), with the ZnLO+P rats running more kilometers per week than the
      ZnLO rats by Week 6. In vivo DEXA analyses indicate that rats fed phytase
      supplemented diets had higher lean body mass (LBM) than those fed ZnLO diets; and
      that rats fed the Zn-adequate diets had the highest LBM. Body fat (%) was
      significantly lower in EX rats and was both Zn- and phytase insensitive. Rats fed
      phytase-supplemented diets had higher bone mineral content (BMC), bone area (BA)
      and BMD than rats fed ZnLO diets; and in rats fed ZnAD diets these indices were
      the highest. The dietary effects on BMC, BA and BMD were independent of activity
      level. We conclude that consuming supplemental dietary phytase or dietary Zn
      additively enhances Zn status to increase BMD, LBM and voluntary physical
      activity in rats fed a low-Zn diet. While the findings confirm that bone health
      is vulnerable to disruption by moderate Zn deficiency in rats, this new data
      suggests that if dietary Zn is limiting, supplemental phytase may have beneficial
      effects on LBM and performance activity.

PMID- 19576753
TI  - Comparison of percolation to batch and sequential leaching tests: theory and
      data.
AB  - Leaching tests are becoming more relevant in assessing solid waste material,
      particularly with respect to groundwater risks. In the field, water infiltration
      is the dominant leaching mechanism, which is simulated in the lab with batch and
      column tests. In this study, we compared percolation, through analytical
      solutions of the advection-dispersion equation, to laboratory batch and
      sequential leaching tests. The analytical solutions are supported with
      comprehensive data from various field and laboratory leaching of different
      solutes from waste materials and soils collected in long-term joint research
      projects funded by the German Federal Ministry for Education and Research and the
      Federal Environment Agency. The comparison of theory and data is facilitated if
      concentrations and cumulative release are plotted versus the liquid-solid ratios
      (LS). Both theory and data indicate that leaching behaviour is independent of
      duration and physical dimensions of the leaching tests. This holds even if field
      lysimeters are compared to laboratory columns of different size, different flow
      velocities as well as different contact times. In general, laboratory batch tests
      over predict effluent concentrations (for LS<K(d)). Leaching of solutes from
      solid samples of certain materials (e.g. chloride from incineration ashes or
      sulphate from demolition waste) in column and lysimeter tests compares very well
      and agrees with the analytical solutions. Overall, reproducibility and agreement
      with theory of column tests are better than batch tests, presumably because the
      latter are prone to artefacts (e.g. in liquid-solid separation steps). Theory and
      data fit surprisingly well, despite the fact that the theory is based on the
      local equilibrium assumption; non-linear sorption and chemical reactions in the
      solid waste materials are not considered.

PMID- 19576754
TI  - A novel biofuel cell harvesting energy from activated human macrophages.
AB  - Macrophage phagocytosis activates NADPH oxidase, an electron transport system in
      the plasma membrane. This study examined the feasibility of utilizing electrons
      transferred through the plasma membrane via NADPH oxidase to run a biofuel cell.
      THP-1 human monocytic cells were chemically stimulated to differentiate into
      macrophages. Further they were activated to induce a phagocytic response. During
      differentiation, cells became adherent to a plain gold electrode which was used
      as anode in a two-compartment fuel cell system. The current production in the
      fuel cell always corresponded to the NADPH oxidase activity, which was evaluated
      by the amount of superoxide anion produced upon stimulation in combination with
      the expression levels of the different NADPH oxidase subunits in cells. Moreover,
      our results of different inhibitory tests let us conclude that (i) the current
      observed in the fuel cell originates from NADPH oxidase in activated macrophages
      and (ii) there are multiple electron transport pathways from the cells to the
      electrode. One pathway involves superoxide anions produced upon stimulation,
      additional not yet identified electron transport occurs independently of
      superoxide anions.This type of novel biofuel cell driven by living human cells
      may eventually develop into a battery replacement for small medical devices.

PMID- 19576755
TI  - Real-time monitoring of the strand displacement amplification (SDA) of human
      cytomegalovirus by a new SDA-piezoelectric DNA sensor system.
AB  - Nucleic acid amplification has long been used in biosensor technologies, such as
      DNA sensors, DNA chips and microarrays, due to its advantage of high sensitivity
      in detecting target DNA. However, dynamic monitoring of nucleic acid
      amplifications with traditional DNA sensors in real-time is difficult since a
      constant temperature must be maintained during detection. Thus, the piezoelectric
      sensor, one type of traditional DNA sensor, is not applicable in real-time
      monitoring PCR due to the dramatic change in temperature that occurs during
      reaction. In this study, we introduced strand displacement amplification (SDA),
      an well-developed nucleic acid amplification technique that can work under
      conditions of constant temperature, into the development of a novel piezoelectric
      sensor. Using the new SDA-piezoelectric DNA sensor, we designed a stable system
      for liquid-phase detection, in which the crystal oscillator plate was fixed by an
      easily adjustable screw-threaded clamping mechanism and successfully applied the
      new sensor system to real-time SDA monitoring of human cytomegalovirus (HCMV).
      This new technique overcomes the shortcomings of traditional DNA sensors in real
      time monitoring of nucleic acid amplification. The technique has proved to be a
      markedly simplified procedure with a number of advantages, such as higher
      sensitivity, better time efficiency, and the ability of dynamic real-time
      detection.

PMID- 19576757
TI  - Cowpea mosaic virus nanoscaffold as signal enhancement for DNA microarrays.
AB  - Previous studies have shown that a functionalized viral nanoparticle can be used
      as a fluorescent signal-generating element and enhance detection sensitivity for
      immunoassays and low density microarrays. In this study, we further tested this
      ability in commercial DNA microarrays, including Affymetrix high density
      resequencing microarray. Optimum conditions for NeutrAvidin and dye coupling to a
      double-cysteine mutant of cowpea mosaic virus (CPMV) were found to be comparable
      to the commonly used streptavidin-phycoerythrin (SAPE) for high density
      resequencing microarray. A 3-fold signal enhancement in comparison to Cy5-dCTP
      controls was obtained when using nanoparticles on control scorecard expression
      microarrays. Hybridization results from commercially available 8000 rat
      expression arrays indicate an increment of 14% on the detected features when the
      virus complex was used as the staining reagent in comparison to Cy5-dCTP
      controls. The current work shows the utility of the CPMV-dye nanoparticles as a
      detection reagent in well-established detection platforms.

PMID- 19576758
TI  - Microelectrode array evaluation of gut pacemaker activity in wild-type and W/W(v)
      mice.
AB  - Interstitial cells of Cajal in the myenteric plexus region (ICC-MyP) form a
      network and generate basal pacemaking electrical activity. This morphological
      feature leads us to believe that these cells may be essential for the
      coordinating actions of gastrointestinal (GI) motility. We aim to propose a new
      method for functional assessment of ICC electrical activity and its network.
      Field potentials in a approximately 1 mm(2) region were simultaneously measured
      using an 8x8 microelectrode array (MEA) with a polar distance of 150 microm. The
      extracellular solution contained nifedipine and tetrodotoxin (TTX) to suppress
      activities of smooth muscle cells and neurons, respectively. We compared spatial
      electrical activities between ileal muscle preparations from wild-type (WT) and
      W/W(v) mice. In spatio-temporal analyses, basal electrical activities were well
      synchronized with a propagation delay in WT, while those in W/W(v) were small in
      amplitude and irregular in occurrence. The power spectrum in WT had a prominent
      peak corresponding to the frequency of ICC-MyP pacemaker activity, while that of
      W/W(v) lacked it. Consequently, the ratio of the spectral power in 9.4-27.0 cpm
      was significantly larger in WT than in W/W(v). In conclusion, MEA measurements
      demonstrated that the network-forming ICC-MyP not only generates but also
      coordinates basal electrical activities. Disorders of GI motility based on
      morphological and functional impairments of ICC network with the range of several
      hundreds of micrometers, could be uncovered in future extensive studies.

PMID- 19576759
TI  - Gold nanoparticles based dipstick immunoassay for the rapid detection of
      dichlorodiphenyltrichloroethane: an organochlorine pesticide.
AB  - Gold nanoparticles (GNPs) based dipstick competitive immunoassay was developed to
      detect organochlorine pesticide such as DDT at nanogram level (ppb). GNPs of
      definite size were synthesized and conjugated to anti-DDT antibodies (IgY), which
      served as the detecting reagent. DDA-BSA conjugate (antigen) was immobilized on
      to nitro cellulose (NC) membrane containing strip. GNPs conjugated anti-DDT
      antibodies were treated with different concentrations of free DDT ranging from
      0.7 ng mL(-1) to 1000 ng mL(-1) to form an immunocomplex. This immunocomplex
      solution was further reacted with DDA-BSA conjugate immobilized NC membrane
      containing strips by dipping the strip in the immunocomplex solution. The free
      GNPs conjugated anti-DDT antibodies present in the immunocomplex solution were
      targeted for competitive binding with immobilized DDA-BSA on NC membrane
      containing strip. Depending on the concentration of free DDT in the sample the
      binding of GNPs conjugated anti-DDT antibodies to the immobilized DDA-BSA varied
      and was detected by the development of red color (due to gold nanoparticles) in
      the detection zone of NC membrane containing strips. The intensity of color
      development was inversely proportional to the DDT concentration with maximum
      intensity at zero DDT concentration. The lowest detection limit of DDT was
      determined to be 27 ng mL(-1) with the optimized conditions. The dipstick
      technique based on GNPs is suitable for the detection of several toxins in food
      and environmental samples and can be applied for rapid on-site testing of
      pesticides.

PMID- 19576756
TI  - Nano-bio-chips for high performance multiplexed protein detection: determinations
      of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels.
AB  - The integration of semiconductor nanoparticle quantum dots (QDs) into a modular,
      microfluidic biosensor for the multiplexed quantitation of three important cancer
      markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and Her
      2/Neu (C-erbB-2) was achieved. The functionality of the integrated sample
      processing, analyte capture and detection modalities was demonstrated using both
      serum and whole saliva specimens. Here, nano-bio-chips that employed a
      fluorescence transduction signal with QD-labeled detecting antibody were used in
      combination with antigen capture by a microporous agarose bead array supported
      within a microfluidics ensemble so as to complete the sandwich-type immunoassay.
      The utilization of QD probes in this miniaturized biosensor format resulted in
      signal amplification 30 times relative to that of standard molecular fluorophores
      as well as affording a reduction in observed limits of detection by nearly 2
      orders of magnitude (0.02 ng/mL CEA; 0.11 pM CEA) relative to enzyme-linked
      immunosorbent assay (ELISA). Assay validation studies indicate that measurements
      by the nano-bio-chip system correlate to standard methods at R(2)=0.94 and
      R(2)=0.95 for saliva and serum, respectively. This integrated nano-bio-chip assay
      system, in tandem with next-generation fluorophores, promises to be a sensitive,
      multiplexed tool for important diagnostic and prognostic applications.

PMID- 19576760
TI  - Prostate Cancer. Preface.

PMID- 19576761
TI  - Buffer requirements for enhanced hydrogen production in acidogenic digestion of
      food wastes.
AB  - The requirements for pH buffer addition for hydrogen production and acidogenesis
      in batch acidogenic digestion of a food waste (FW) feedstock with limited
      alkalinity was studied at various initial pH conditions (6.0-8.0). The results
      showed that, without buffer addition, hydrogen production from this feedstock was
      insignificant regardless of the initial pH. With buffer addition, hydrogen
      production improved significantly if the initial pH was greater than 6.0.
      Substantial hydrogen production occurred when the pH at the end of the batch
      digestion was higher than 5.5. The maximum hydrogen production was found to be
      120 mL/g VS added when the initial pH was 6.5 and buffer addition was in the
      range of 15-20 mmol/g VS. The effect of pH buffering on the formation of volatile
      fatty acids (acetic acid, propionic acid and butyric acid) was similar to its
      effect on hydrogen production. The results of this study clearly indicated shifts
      in the metabolic pathways with the pH of fermentation. The changes in metabolic
      pathways impacted upon the dosage of buffer that was required to achieve maximum
      hydrogen generation.

PMID- 19576762
TI  - An accurate and non-labor intensive method for the determination of syringyl to
      guaiacyl ratio in lignin.
AB  - The syringyl to guaiacyl (S:G) ratio of hardwood lignin has long been identified
      as a significant parameter in delignification processes and more recent results
      have shown that it is also important in determining the amount of ethanol that
      can be obtained from fermentation of hydrolyzed wood. Acidolysis of Klason or
      acid insoluble lignin in dioxane/water/HCl was being investigated when syringyl
      and guaiacyl nuclei with a diketone-containing sidechain were observed as the
      major products. The area ratio of the two gas chromatogram peaks appeared to be
      indicative of the S:G ratio. After optimization of the method the relative
      standard deviation was found to be in the range of 0.3-3.76% for Klason lignin
      from a wide range of Eucalyptus grandis grown in South Africa. The method was
      then compared to nitrobenzene oxidation (NBO) using 13 poplars in a double-blind
      study. The respective S:G ratios were used to calculate percentages of S units
      and when these values were plotted against each other a linear correlation was
      obtained with a slope of approximately 1.0 (R(2)=0.86). The largest discrepancy
      for any poplar was 6.9% (62% vs. 58% S units). Both methods convincingly
      demonstrated a significant decrease in lignin content with an increase in the S:G
      ratio. Discussion is presented on a series of reaction that could lead to the
      formation of the two diketones.

PMID- 19576763
TI  - Clonal response to cold tolerance in creeping bentgrass and role of proline
      associated pentose phosphate pathway.
AB  - Single seed origin creeping bentgrass ('Penncross') clonal lines were screened to
      find genetic heterogeneity, which reflected diversity of phenolic production
      linked to cold stress within a cross-pollinated cultivar. In this study, total
      soluble phenolic and antioxidant activity varied among 20 creeping bentgrass
      clonal lines, confirming wide heterogeneity in this cross-pollinated species.
      Correlations between phenolic content and proline-associated pentose phosphate
      pathway were also found among the clonal lines. The active metabolic role of
      proline in cellular metabolic adjustment to cold stress and its support for
      likely energy synthesis via mitochondrial oxidative phosphorylation was inferred
      in creeping bentgrass clonal lines based on the activity of proline
      dehydrogenase. Results of photochemical efficiency of these clonal lines after
      cold temperature treatment (4 degrees C) also indicated a close association
      between stress tolerance and proline-associated pentose phosphate pathway
      regulation for phenolic biosynthesis and antioxidant response. This study
      provides a sound metabolic based rationale to screen bentgrass clonal lines for
      enhanced cold stress tolerance.

PMID- 19576764
TI  - Tannin-based rigid foams: a survey of chemical and physical properties.
AB  - Tannin-based rigid foams, prepared from 95% natural material, are suggested for
      replacing synthetic phenol-formaldehyde foams in various applications. For that
      purpose, a few physical properties were measured and reported here: resistance to
      fire and chemicals, absorption of various liquids, permeability, thermal
      conductivity and mechanical (compressive and tensile) strength. Modifying the
      composition through the use of boric and/or phosphoric acid allowed substantial
      increase of fire resistance. The materials were also found to present good
      resistance to strong acid and bases, and to solvents. High affinity for water,
      but limited one for organic liquids, was also evidenced. Finally, slightly
      anisotropic mechanical properties were measured. The materials present a brittle
      behaviour, whether tested in compression or traction; nevertheless, their
      strengths, as well as their thermal conductivities, are fully comparable with
      those of their phenolic counterparts. We show that such materials of vegetable
      origins can compete with synthetic ones for most of traditional applications.

PMID- 19576765
TI  - Design and synthesis of BACE-1 inhibitors utilizing a tertiary hydroxyl motif as
      the transition state mimic.
AB  - Two series of drug-like BACE-1 inhibitors with a shielded tertiary hydroxyl as
      transition state isostere have been synthesized. The most potent inhibitor
      exhibited a BACE-1 IC(50) value of 0.23 microM.

PMID- 19576766
TI  - Synthesis and SAR studies of 1,4-diazabicyclo[3.2.2]nonane phenyl carbamates-
      subtype selective, high affinity alpha7 nicotinic acetylcholine receptor
      agonists.
AB  - The synthesis and SAR studies about the bicyclic amine, carbamate linker and
      aromatic ring of a 1,4-diazabicyclo[3.2.2]nonane phenyl carbamate series of
      alpha7 nAChR agonists is described. The development of the medicinal chemistry
      strategy and SAR which led to the identification of 5 and 7aa as subtype
      selective, high affinity alpha7 agonists as excellent leads for further
      evaluation is discussed, along with key physicochemical and pharmacokinetic data
      highlighting their lead potential.

PMID- 19576767
TI  - From lead to preclinical candidate: optimization of beta-homophenylalanine based
      inhibitors of dipeptidyl peptidase IV.
AB  - A series of highly potent and selective inhibitors of DPP-4 was optimized for
      ADMET properties. The effort resulted in the discovery of inhibitor 1g, that
      exhibits excellent efficacy in an oral glucose tolerance test and an attractive
      pharmacokinetic profile.

PMID- 19576768
TI  - Gibberellin signaling controls cell proliferation rate in Arabidopsis.
AB  - Plant growth involves the integration of many environmental and endogenous
      signals that together with the intrinsic genetic program determine plant size. At
      the cellular level, growth rate is regulated by the combined activity of two
      processes: cell proliferation and expansion. Gibberellins (GA) are plant-specific
      hormones that play a central role in the regulation of growth and development
      with respect to environmental variability. It is well established that GA promote
      growth through cell expansion by stimulating the destruction of growth-repressing
      DELLA proteins (DELLAs); however, their effects on cell proliferation remain
      unknown. Kinematic analysis of leaf and root meristem growth revealed a novel
      function of DELLAs in restraining cell production. Moreover, by visualizing the
      cell cycle marker cyclinB1::beta-glucuronidase in GA-signaling mutants, we show
      that GA modulate cell cycle activity in the root meristem via a DELLA-dependent
      mechanism. Accordingly, expressing gai (a nondegradable DELLA protein) solely in
      root meristem reduced substantially the number of dividing cells. We also show
      that DELLAs restrain cell production by enhancing the levels of the cell cycle
      inhibitors Kip-related protein 2 (KRP2) and SIAMESE (SIM). Therefore, DELLAs
      exert a general plant growth inhibitory activity by reducing both cell
      proliferation and expansion rates, enabling phenotypic plasticity.

PMID- 19576769
TI  - Flies require bilateral sensory input to track odor gradients in flight.
AB  - Fruit flies make their living "on the fly" in search of attractive food odors.
      Flies balance the strength of self-induced bilateral visual motion and bilateral
      wind cues, but it is unknown whether they also use bilateral olfactory cues to
      track odors in flight. Tracking an odor gradient requires comparisons across
      spatially separated chemosensory organs and has been observed in several walking
      insects, including Drosophila. The olfactory antennae are separated by a fraction
      of a millimeter, and most sensory neurons project bilaterally and also
      symmetrically activate the first-order olfactory relay; both properties would
      seem to constrain the capacity for gradient tracking. Nevertheless, using a
      modified flight simulator that enables maneuvers in the yaw axis, we found that
      flies readily steer directly toward a laterally positioned odor plume. This
      capability is abolished by occluding sensory input to one antenna. Mechanosensory
      input from the Johnston's organ and olfactory input from the third antennal
      segment cooperate to direct small-angle yaw turns up the plume gradient. We
      additionally show that sensory signals from the left antenna contribute
      disproportionately more to odor tracking than signals from the right, providing
      further evidence of sensory lateralization in invertebrates.

PMID- 19576770
TI  - Gibberellin signaling in the endodermis controls Arabidopsis root meristem size.
AB  - Plant growth is driven by cell proliferation and elongation. The hormone
      gibberellin (GA) regulates Arabidopsis root growth by controlling cell
      elongation, but it is currently unknown whether GA also controls root cell
      proliferation. Here we show that GA biosynthetic mutants are unable to increase
      their cell production rate and meristem size after germination. GA signals the
      degradation of the DELLA growth repressor proteins GAI and RGA, promoting root
      cell production. Targeting the expression of gai (a non-GA-degradable mutant form
      of GAI) in the root meristem disrupts cell proliferation. Moreover, expressing
      gai in dividing endodermal cells was sufficient to block root meristem
      enlargement. We report a novel function for GA regulating cell proliferation
      where this signal acts by removing DELLA in a subset of, rather than all,
      meristem cells. We suggest that the GA-regulated rate of expansion of dividing
      endodermal cells dictates the equivalent rate in other root tissues. Cells must
      double in size prior to dividing but cannot do so independently, because they are
      physically restrained by adjacent tissues with which they share cell walls. Our
      study highlights the importance of probing regulatory mechanisms linking
      molecular- and cellular-scale processes with tissue and organ growth responses.

PMID- 19576771
TI  - C. elegans are protected from lethal hypoxia by an embryonic diapause.
AB  - At least 100 mammalian species exhibit embryonic diapause, where fertilized
      embryos arrest development in utero until suitable seasonal or nutritional
      environments are encountered. Delaying maternal investments in producing
      offspring allows these animals to utilize limited resources to survive while
      searching for better conditions and ensures that progeny are not produced when
      they are unlikely to survive. In addition, embryos may be protected from external
      environmental vicissitudes while in utero. Here we demonstrate embryonic diapause
      in C. elegans, and show that this diapause protects embryos from otherwise lethal
      hypoxia. Diapausing embryos in utero require san-1 to survive, indicating that
      hypoxia-induced embryonic diapause may be mechanistically related to suspended
      animation. Furthermore, we show that neuronal HIF-1 activity in the adult
      dictates the O(2) tension at which embryonic diapause is engaged. We suggest that
      the maternal perception of hypoxia stimulates a response to protect embryos in
      utero by inducing diapause, a natural form of suspended animation. This response
      is likely to be an important strategy to improve offspring survival in harsh
      conditions and allow adults to find environments more suitable for reproductive
      success.

PMID- 19576773
TI  - Mushroom bodies regulate habit formation in Drosophila.
AB  - To make good decisions, we evaluate past choices to guide later decisions. In
      most situations, we have the opportunity to simultaneously learn about both the
      consequences of our choice (i.e., operantly) and the stimuli associated with
      correct or incorrect choices (i.e., classically). Interestingly, in many species,
      including humans, these learning processes occasionally lead to irrational
      decisions. An extreme case is the habitual drug user consistently administering
      the drug despite the negative consequences, but we all have experience with our
      own, less severe habits. The standard animal model employs a combination of
      operant and classical learning components to bring about habit formation in
      rodents. After extended training, these animals will press a lever even if the
      outcome associated with lever-pressing is no longer desired. In this study,
      experiments with wild-type and transgenic flies revealed that a prominent insect
      neuropil, the mushroom bodies (MBs), regulates habit formation in flies by
      inhibiting the operant learning system when a predictive stimulus is present.
      This inhibition enables generalization of the classical memory and prevents
      premature habit formation. Extended training in wild-type flies produced a
      phenocopy of MB-impaired flies, such that generalization was abolished and goal
      directed actions were transformed into habitual responses.

PMID- 19576772
TI  - Location-specific cortical activation changes during sleep after training for
      perceptual learning.
AB  - Visual perceptual learning is defined as performance enhancement on a sensory
      task and is distinguished from other types of learning and memory in that it is
      highly specific for location of the trained stimulus. The location specificity
      has been shown to be paralleled by enhancement in functional magnetic resonance
      imaging (fMRI) signal in the trained region of V1 after visual training. Although
      recently the role of sleep in strengthening visual perceptual learning has
      attracted much attention, its underlying neural mechanism has yet to be
      clarified. Here, for the first time, fMRI measurement of human V1 activation was
      conducted concurrently with a polysomnogram during sleep with and without
      preceding training for visual perceptual learning. As a result of predetermined
      region-of-interest analysis of V1, activation enhancement during non-rapid-eye
      movement sleep after training was observed specifically in the trained region of
      V1. Furthermore, improvement of task performance measured subsequently to the
      post-training sleep session was significantly correlated with the amount of the
      trained-region-specific fMRI activation in V1 during sleep. These results suggest
      that as far as V1 is concerned, only the trained region is involved in improving
      task performance after sleep.

PMID- 19576775
TI  - Regulation of centrosome separation in yeast and vertebrates: common threads.
AB  - The assembly of a bipolar spindle is crucial for symmetric partitioning of
      duplicated chromosomes during cell division. Centrosomes (spindle pole body [SPB]
      in yeast) constitute the two poles of this bipolar structure and serve as
      microtubule nucleation centers. A eukaryotic cell enters the division cycle with
      one centrosome and duplicates it before spindle formation. A proteinaceous link
      keeps duplicated centrosomes together until it is severed at onset of mitosis,
      enabling centrosomes to migrate away from each other and assemble a
      characteristic mitotic spindle. Hence, centrosome separation is crucial in
      assembly of a bipolar spindle. Whereas centrosome (or SPB) duplication has been
      characterized in some detail, the separation process is less well understood.
      Here, we review recent studies that uncover new players and provide a greater
      understanding of the regulation of centrosome (or SPB) separation.

PMID- 19576774
TI  - Reward motivation accelerates the onset of neural novelty signals in humans to 85
      milliseconds.
AB  - The neural responses that distinguish novel from familiar items in recognition
      memory tasks are remarkably fast in both humans and nonhuman primates. In humans,
      the earliest onsets of neural novelty effects emerge at about approximately 150
      200 ms after stimulus onset. However, in recognition memory studies with nonhuman
      primates, novelty effects can arise at as early as 70-80 ms. Here, we address the
      possibility that this large species difference in onset latencies is caused
      experimentally by the necessity of using reward reinforcement to motivate the
      detection of novel or familiar items in nonhuman primates but not in humans. Via
      magnetoencephalography in humans, we show in two experiments that the onset of
      neural novelty signals is accelerated from approximately 200 ms to approximately
      85 ms if correct recognition memory for either novel or familiar items is
      rewarded. Importantly, this acceleration is independent of whether the detection
      of the novel or the familiar scenes is rewarded. Furthermore, this early novelty
      effect contributed to memory retrieval because neural reward responses, which
      were contingent upon novelty detection, followed approximately 100 ms later.
      Thus, under the contextual influence of reward motivation, behaviorally relevant
      novelty signals emerge much faster than previously held possible in humans.

PMID- 19576776
TI  - Experimental study on the role of the ankle push off in the walk-to-run
      transition by means of a powered ankle-foot-exoskeleton.
AB  - The goal of this study was to analyse the role of the plantarflexor muscles in
      the walk-to-run transition (WRT) by means of a powered ankle-foot-exoskeleton. 11
      female subjects performed several WRT's on an accelerating treadmill while their
      plantarflexors were assisted or resisted during push off. The WRT speed was lower
      in the resist condition than in the control condition which reinforces hypotheses
      from previous simulations, descriptive and experimental studies. There was no
      increase in WRT speed in the assist condition which is in contrast to another
      study where the plantarflexor push off was assisted indirectly by a horizontal
      traction at waist level. The lack of effect from the assist condition in the
      present study is possibly due to the narrowly focused nature of the experimental
      manipulation.

PMID- 19576777
TI  - Gene Ontology for type III effectors: capturing processes at the host-pathogen
      interface.
AB  - Disease development is determined by the interplay of host defense processes and
      pathogen factors that subvert defenses and remodel the host for parasitic
      benefit. The goal of the Plant-Associated Microbe Gene Ontology (PAMGO) interest
      group is the development of Gene Ontology (GO) terms that capture the range of
      biological processes occurring between hosts and symbionts (from mutualists to
      pathogens). Here, the application of the new GO terms to type III effector
      proteins (T3Es) from the plant pathogen Pseudomonas syringae serves as an example
      to systematically document the available extensive data and to reveal shared
      aspects of interactions with various host plants. Extending the comparison to
      T3Es deployed by animal pathogens further highlights how GO can uncover the
      common strategies employed by diverse symbionts as they exploit the host niche.
      Future application of GO terms to gene products mediating pathogenic or
      mutualistic interactions involving other microbes will enhance researchers'
      abilities to identify fundamental patterns among diverse systems and generate new
      hypotheses based on associations among annotations.

PMID- 19576779
TI  - Describing commonalities in microbial effector delivery using the Gene Ontology.
AB  - Myriad symbiotic microbes, ranging from mutualistic through to pathogenic,
      deliver 'effector' molecules into the cytoplasm or cellular milieu of their hosts
      to facilitate colonization. Among ecologically and evolutionarily diverse taxa,
      analogous processes and structures exist to facilitate effector delivery. These
      include syringe-like injection (bacteria and nematodes), common host-targeting
      signals (oomycetes and protozoans) and specialized intercellular structures
      (fungi and oomycetes). Here, we briefly introduce readers to the Gene Ontology
      (GO), a controlled vocabulary to facilitate comparative genomics of diverse taxa.
      We also summarize and compare selected mechanisms of effector delivery from
      various organisms and show how careful annotation of gene products with GO can
      reveal underlying similarities among diverse taxa.

PMID- 19576778
TI  - What we can learn about Escherichia coli through application of Gene Ontology.
AB  - How we classify the genes, products and complexes that are present or absent in
      genomes, transcriptomes, proteomes and other datasets helps us place biological
      objects into subsystems with common functions, see how molecular functions are
      used to implement biological processes and compare the biology of different
      species and strains. Gene Ontology (GO) is one of the most successful systems for
      classifying biological function. Although GO is widely used for eukaryotic
      genomics, it has not yet been widely used for bacterial systems. The potential
      applications of GO are currently limited by the need to improve the annotation of
      bacterial genomes with GO and to improve how prokaryotic biology is represented
      in the ontology. Here, we discuss why GO should be adopted by microbiologists,
      and describe recent efforts to build and maintain high-quality GO annotation for
      Escherichia coli as a model system.

PMID- 19576780
TI  - Cerebellar swelling after sacrifice of the superior petrosal vein during
      microvascular decompression for trigeminal neuralgia.
AB  - The importance of preserving the deep cerebral venous outflow has been recognized
      in microvascular decompression for trigeminal neuralgia; however, few reports
      have described the details of complications arising from the sacrifice of the
      superior petrosal vein (SPV). During the procedure in a 77-year-old woman, some
      tributaries of the SPV complex were sacrificed to achieve microvascular
      decompression for right trigeminal neuralgia. Postoperatively, the patient was
      conscious and pain free; however, on postoperative day 1 she developed headache
      and nausea followed by a decreased level of consciousness. MRI revealed an
      extensive venous infarction in the right cerebellum. Sacrifice of the SPV may
      lead to serious, potentially life-threatening complications. Neurosurgeons should
      pay close attention to the management of the SPV to reduce the risk of venous
      complications.

PMID- 19576781
TI  - Delayed toxicity from gamma knife radiosurgery to lesions in and adjacent to the
      brainstem.
AB  - The aims of this study were to assess the incidence of, and risk factors for,
      delayed toxicity following gamma knife stereotactic radiosurgery (GKRS) to
      lesions in and adjacent to the brainstem. We retrospectively evaluated the
      delayed toxicity of GKRS following the treatment of 114 lesions in and adjacent
      to the brainstem in 107 patients. The median tumor volume was 6.2 cm(3) and the
      median dose to the tumor margin was 16Gy. The mean follow-up was 40 months.
      Thirteen patients (12%) demonstrated clinical evidence of delayed toxicity, with
      a median latency to the development of toxicity of 6 months. The actuarial
      incidence of toxicity at 1 year and 5 years was 10.2% and 13.8%. Larger tumor
      volume (p=0.02) and larger treatment volume (p=0.04) were associated with an
      increased incidence of delayed toxicity. Large lesions adjacent to the brainstem
      have a higher than previously suspected rate of delayed toxicity.

PMID- 19576782
TI  - Two children with traumatic thoracic spinal epidural hematoma.
AB  - Traumatic spinal epidural hematomas in children are uncommon. Early diagnosis and
      prompt surgical evacuation is critical in these patients. We report two children
      with traumatic thoracic spine epidural hematomas with remarkable neurological
      recovery after surgical evacuation. Epidural hematoma with significant cord
      compression requires early diagnosis and emergency evacuation. This is crucial to
      expedite neurological recovery.

PMID- 19576783
TI  - Epidemiology of joint disorders in Parkinson's disease and their impact on health
      status.

PMID- 19576784
TI  - Epilepsy and temporal lobe injury after skull base proton beam therapy.
AB  - We present three patients who developed temporal lobe injury and epilepsy after
      proton beam therapy to the skull base. This particular form of treatment-related
      toxicity should be considered when treating skull base tumors.

PMID- 19576785
TI  - Potent antitumor bifunctional DNA alkylating agents, synthesis and biological
      activities of 3a-aza-cyclopenta[a]indenes.
AB  - A series of bifunctional DNA interstrand cross-linking agents, bis(hydroxymethyl)
      and bis(carbamates)-8H-3a-azacyclopenta[a]indene-1-yl derivatives were
      synthesized for antitumor evaluation. The preliminary antitumor studies revealed
      that these agents exhibited potent cytotoxicity in vitro and antitumor
      therapeutic efficacy against human tumor xenografts in vivo. Furthermore, these
      derivatives have little or no cross-resistance to either Taxol or Vinblastine.
      Remarkably, complete tumor remission in nude mice bearing human breast carcinoma
      MX-1 xenograft by 13a,b and 14g,h and significant suppression against prostate
      adenocarcinoma PC3 xenograft by 13b were achieved at the maximum tolerable dose
      with relatively low toxicity. In addition, these agents induce DNA interstrand
      cross-linking and substantial G2/M phase arrest in human non-small lung carcinoma
      H1299 cells. The current studies suggested that these agents are promising
      candidates for preclinical studies.

PMID- 19576788
TI  - Extraction of Hg(I), Hg(II) and methylmercury using polyethylene glycol based
      aqueous biphasic system.
AB  - Extraction behavior of three different salts of mercury, HgCl(2), Hg(2)Cl(2) and
      CH(3)HgCl, were studied in a polyethylene glycol based aqueous biphasic
      extraction system (ABS). The results were compared with extraction pattern in a
      liquid-liquid system using methylisobutyl ketone (MIBK), against HCl and a solid
      chelating ion exchanger, Chelex 100. The results showed a variable extent of
      partitioning of different salts of mercury using MIBK and Chelex 100 as ion
      exchangers. However, when ABS was employed, complete extractions of all the three
      species of mercury were achieved irrespective of their chemical form.

PMID- 19576787
TI  - The structure of the scaffold nucleoporin Nup120 reveals a new and unexpected
      domain architecture.
AB  - Nucleocytoplasmic transport is mediated by nuclear pore complexes (NPCs),
      enormous protein assemblies residing in circular openings in the nuclear
      envelope. The NPC is modular, with transient and stable components. The stable
      core is essentially built from two multiprotein complexes, the Y-shaped
      heptameric Nup84 complex and the Nic96 complex, arranged around an eightfold
      axis. We present the crystal structure of Nup120(1-757), one of the two short
      arms of the Y-shaped Nup84 complex. The protein adopts a compact oval shape built
      around a novel bipartite alpha-helical domain intimately integrated with a beta
      propeller domain. The domain arrangement is substantially different from the
      Nup85*Seh1 complex, which forms the other short arm of the Y. With the data
      presented here, we establish that all three branches of the Y-shaped Nup84
      complex are tightly connected by helical interactions and that the beta
      propellers likely form interaction site(s) to neighboring complexes.

PMID- 19576786
TI  - Identification, structure-activity relationships and molecular modeling of potent
      triamine and piperazine opioid ligands.
AB  - Opioid receptors are important targets for pain management. Here, we report the
      synthesis and biological evaluation of three positional scanning combinatorial
      libraries, consisting of linear triamines and piperazines. A highly potent (14
      nM) and selective (IC(50(mu))/IC(50(kappa))=71; IC(50(delta))/IC(50(kappa))=714)
      triamine for the kappa-opioid receptor was found. In addition, non-selective mu
      kappa binders were obtained, with binding affinities of 54 nM and 22 nM for mu-
      and kappa-opioid receptors, respectively. Structure-activity relationships of
      each subset are described. 3D molecular alignments based on shape similarity to
      internal and external query molecules were carried out. For the combinatorial
      chemistry dataset studied here a 1.3 similarity cut-off value was observed to be
      efficient in the rocs-based alignment method. Interactions from the overlays
      analyzed in the binding sites of homology models of the receptors revealed
      specific substitution patterns for enhancing binding affinity in the piperazine
      series. Pharmacophore modeling of the compounds found from the three
      combinatorial libraries was also performed. The pharmacophore model indicated
      that the important feature for receptor binding activity with the mu-receptor was
      the presence of at least one hydrogen bond acceptor and one aromatic hydrophobic
      group. Whereas for the kappa-receptor two binding modes emerged with one set of
      compounds employing the hydrogen bond acceptor and aromatic hydrophobic group,
      and a second set possibly via interactions with the receptor by hydrophobic and
      ionic salt-bridges.

PMID- 19576789
TI  - Leaf photosynthetic and solar-tracking responses of mallow, Malva parviflora, to
      photon flux density.
AB  - Malva parviflora L. (mallow) is a species that occupies high-light habitats as a
      weedy invader in orchards and vineyards. Species of the Malvaceae are known to
      solar track and anecdotal evidence suggests this species may also. How M.
      parviflora responds physiologically to light in comparison with other species
      within the Malvaceae remains unknown. Tracking and photosynthetic responses to
      photon flux density (PFD) were evaluated on plants grown in greenhouse
      conditions. Tracking ability was assessed in the growth conditions and by
      exposing leaves to specific light intensities and measuring changes in the angle
      of the leaf plane. Light responses were also determined by photosynthesis and
      chlorophyll fluorescence. Leaves followed a heliotropic response which was highly
      PFD-dependent, with tracking rates increasing in a curvilinear pattern. Maximum
      tracking rates were up to 20 degrees h(-1) and saturated for light above 1,300
      micromol (photons) m(-2) s(-1). This high-light saturation, both for tracking
      (much higher than the other species), and for photosynthesis, confirmed mallow as
      a high-light demanding species. Further, because there was no photoinhibition,
      the leaves could capture the potential of an increased carbon gain in higher
      irradiance by resorting to solar tracking. Modelling suggested the tracking
      response could increase the annual carbon gain by as much as 25% compared with
      leaves that do not track the sun. The various leaf attributes associated with
      solar tracking, therefore, help to account for the success of this species as a
      weed in many locations worldwide.

PMID- 19576790
TI  - Primary intraosseous squamous cell carcinomas: five new clinicopathologic case
      studies.
AB  - Primary intraosseous squamous cell carcinomas (PIOSCCs) are rare malignant
      tumours which arise from odontogenic epithelial remnants. Herein we report five
      new PIOSCC cases, affecting three female and two male patients with a mean age of
      64.4 years. One case involved the maxilla and four cases occurred in the
      mandible. Typical radiographic findings were ill-defined radiolucencies.
      Histopathologically, four cases were diagnosed as well-differentiated PIOSCCs
      arising de novo or from odontogenic cysts. The remaining case was a moderately
      differentiated de novo PIOSCC. In four cases, treatment consisted of surgical
      removal with perioperative radiotherapy or chemotherapy. To date, there have been
      no recurrences or distant metastases in three cases. The lesion was not locally
      controlled in one case and curative treatments were rejected in another case.
      PIOSCCs are thought to be important among radiolucent jaw lesions, and early
      diagnoses and surgical excision with sufficient margins of safety may allow for
      good prognoses.

PMID- 19576791
TI  - Serum levels of monocyte chemoattractant protein-1 in periodontal health and
      disease.
AB  - OBJECTIVES: Initial research has reported high levels of monocyte chemoattractant
      protein-1 (MCP-1) in gingival crevicular fluid (GCF) of periodontitis patients.
      Present study has been carried out to assess its concentration in serum and to
      find its association with periodontal health and disease. DESIGN: 60 subjects
      were divided into three groups (n=20) based on gingival index (GI), probing
      pocket depth (PPD) and clinical attachment loss (CAL): healthy (group I),
      gingivitis (group II) and chronic periodontitis (group III). A fourth group
      (group IV) consisted of 20 subjects from group III, 6-8 weeks after treatment
      [i.e. scaling and root planing (SRP)]. Serum samples obtained from each patient
      were quantified for MCP-1 using enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The mean MCP-1 concentration in serum was found to be the highest in
      group III i.e. 465.80 pg/ml and lowest in group I i.e. 155.20 pg/ml. For group II
      (251.60 pg/ml) and group IV (263.20 pg/ml) the mean MCP-1 concentrations were
      found to lie in between the concentrations obtained in group I and III.
      CONCLUSIONS: Serum MCP-1 concentration was found to be, approximately one and
      half folds higher in gingivitis patients (group II) and three folds higher in
      chronic periodontitis patients (group III) as compared to healthy subjects (group
      I). Further, the MCP-1 concentration increased proportionally with the severity
      of disease in group II and III showing positive correlation with clinical
      parameters. Thus, its role as an inflammatory biomarker in periodontal disease
      can be proposed.

PMID- 19576792
TI  - Modulation of long-term memory by arousal in alexithymia: the role of
      interpretation.
AB  - Moderate physiological or emotional arousal induced after learning modulates
      memory consolidation, helping to distinguish important memories from trivial
      ones. Yet, the contribution of subjective awareness or interpretation of arousal
      to this effect is uncertain. Alexithymia, which is an inability to describe or
      identify one's emotional and arousal states even though physiological responses
      to arousal are intact, provides a tool to evaluate the role of arousal
      interpretation. Participants scoring high and low on alexithymia (N=30 each)
      learned a list of 30 words, followed by immediate recall. Participants then saw
      either an arousing (oral surgery) or neutral video (tooth brushing). Memory was
      tested 24-h later. Physiological response to arousal was comparable between
      groups, but subjective response to arousal was impaired in high alexithymia. Yet,
      delayed word recognition was enhanced by arousal regardless of alexithymia
      status. Thus, subjective response to arousal, i.e., cognitive appraisal, was not
      necessary for memory modulation to occur.

PMID- 19576793
TI  - Antiepileptic drug treatment of children at a referral centre for epilepsy--does
      admission make a difference?
AB  - PURPOSE: To study the antiepileptic drug treatment of children at a referral
      centre for epilepsy, including a follow-up study three months after discharge.
      MATERIAL AND METHODS: The study includes children admitted to The National Centre
      for Epilepsy in Norway. Data were collected from the medical records of 261
      children, and a questionnaire regarding the pharmacological treatment was sent to
      their parents three months after discharge. RESULTS: The most common reasons for
      admission to the referral centre were medical and diagnostic evaluation. New
      antiepileptic drugs were used more frequently than old, in 251 and 158 cases,
      respectively. 53 and 54% were using polytherapy at admission and discharge,
      respectively. Levetiracetam, valproate and lamotrigine were the most frequently
      used antiepileptic drugs before, during, and after the stay at the centre.
      Levetiracetam was the only drug being more frequently used at discharge/three
      months after discharge than at admission. Dosage adjustments were made in 83% of
      the patients following measurement of serum concentrations and clinical
      evaluation. According to the parents the number of adverse effects had been
      reduced by 20% three months after discharge. Likewise 40% stated that their
      children experienced better seizure control, and 47% that their family
      experienced a better everyday life after the stay. CONCLUSION: Close
      comprehensive follow-up of children admitted to the referral centre, with main
      focus on optimalization of the pharmacological treatment, is of importance
      regarding quality of life aspects both to the children and their families.

PMID- 19576794
TI  - Recognition of 5' triphosphate by RIG-I helicase requires short blunt double
      stranded RNA as contained in panhandle of negative-strand virus.
AB  - Antiviral immunity is triggered by immunorecognition of viral nucleic acids. The
      cytosolic helicase RIG-I is a key sensor of viral infections and is activated by
      RNA containing a triphosphate at the 5' end. The exact structure of RNA
      activating RIG-I remains controversial. Here, we established a chemical approach
      for 5' triphosphate oligoribonucleotide synthesis and found that synthetic single
      stranded 5' triphosphate oligoribonucleotides were unable to bind and activate
      RIG-I. Conversely, the addition of the synthetic complementary strand resulted in
      optimal binding and activation of RIG-I. Short double-strand conformation with
      base pairing of the nucleoside carrying the 5' triphosphate was required. RIG-I
      activation was impaired by a 3' overhang at the 5' triphosphate end. These
      results define the structure of RNA for full RIG-I activation and explain how RIG
      I detects negative-strand RNA viruses that lack long double-stranded RNA but do
      contain blunt short double-stranded 5' triphosphate RNA in the panhandle region
      of their single-stranded genome.

PMID- 19576796
TI  - Role of PSA velocity in predicting pathologic upgrade for Gleason 6 prostate
      cancer.
AB  - BACKGROUND: Pathologic upgrading to Gleason 7 or higher on radical prostatectomy
      (RP) specimens occurs in many patients with Gleason 6 prostate cancer on
      preoperative biopsy. We evaluated whether biopsy characteristics and preoperative
      factors, including preoperative PSA velocity (PSAV), are predictive of pathologic
      upgrading. MATERIALS AND METHODS: We identified 235 consecutive Gleason 6
      prostate cancer patients who underwent biopsies at our institution, had multiple
      pre-biopsy PSA values, and eventually underwent RP. Preoperative biopsy, clinical
      characteristics, and PSAV were analyzed to determine the risk of pathologic
      upgrading or extracapsular extension. These clinical factors were evaluated for
      association with biochemical recurrence following RP. RESULTS: Overall, 48% of
      patients were upgraded to Gleason grade 7 or higher following RP. Median PSAV was
      0.61 ng/mL/y, and PSAV was similar between upgraded and non-upgraded patients
      (1.01 vs. 0.78, P = 0.1). PSA velocity level was not associated with
      extracapsular disease (P = 0.4). PSA velocity > 1 was associated with biochemical
      recurrence (HR 3.23, P = 0.01) but this was not statistically significant in a
      multivariable model. Increasing PSA density (HR 2.18, P < 0.001), bilateral cores
      positive (HR 1.89, P < 0.05), and any biopsy core involvement > 50% (HR 2.52, P <
      0.05) were most associated with pathologic upgrading. On multivariate analysis,
      only bilateral cancer detection at biopsy (HR 1.90, P < 0.05) significantly
      predicted upgrading. CONCLUSIONS: PSAV has a limited role in predicting Gleason 6
      upgrading. Patients with bilateral cancer detected on transrectal biopsy should
      be encouraged to have radical local therapy due to high risk of harboring more
      aggressive disease.

PMID- 19576795
TI  - Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated
      proinflammatory macrophage response in vivo.
AB  - The recognition of viral components by host pattern-recognition receptors
      triggers the induction of the antiviral innate immune response. Toll-like
      receptor 9 (TLR9) and NLRP3 inflammasome were shown to be the principal specific
      sensors of viral double-stranded DNA. Here we present evidence that macrophages
      in vivo activated an innate immune response to a double-stranded DNA virus,
      adenovirus (Ad), independently of TLR9 or NLRP3 inflammasome. In response to Ad,
      macrophage-derived IL-1 alpha triggered IL-1RI-dependent production of a defined
      set of proinflammatory cytokines and chemokines. The IL-1 alpha-mediated response
      required a selective interaction of virus arginine-glycine-aspartic acid (RGD)
      motifs with macrophage beta(3) integrins. Thus, these data identify IL-1 alpha-IL
      1RI as a key pathway allowing for the activation of proinflammatory responses to
      the virus, independently of its genomic nucleic acid recognition.

PMID- 19576797
TI  - A multidisciplinary approach to the management of urologic malignancies: does it
      influence diagnostic and treatment decisions?
AB  - OBJECTIVE: It is recognized that multidisciplinary teams may improve management
      decisions for patients with malignancies. We prospectively studied the effect of
      such a multidisciplinary approach on the diagnosis and treatment decisions of
      patients newly presenting with urologic malignancies. METHODS: Two hundred sixty
      nine consecutive new patients presenting to our institution with an outside
      diagnosis of a urologic malignancy for diagnostic or treatment considerations
      (2007-2008). All cases were reviewed and discussed at a tumor board with all
      members of the different subspecialties present. Reevaluation of the outside
      diagnostic and treatment plan was undertaken. Based on this team review and
      approach, patients were classified based on changes in diagnosis and/or
      treatment. RESULTS: Cohort was comprised of patients with the diagnosis of cancer
      of the prostate (34%), bladder (23%), kidney (35%), testicle (5%), and other
      (1%). Only 35% of patients had no changes in diagnosis or treatment, 38% had a
      change in diagnosis or treatment, 10% required further analysis (i.e., "other"),
      and 17% were N/A. Changes in diagnosis were most common in bladder (23%) and
      renal (17%) cancers. Changes in treatment were most common in bladder cancer
      (44%), followed by kidney (36%), testicular (29%), then prostate (22%) cancers. A
      stage effect on diagnostic and treatment considerations was also noted,
      especially for bladder cancer. CONCLUSIONS: A multidisciplinary team approach
      affects the diagnostic and management decisions in a significant number patients
      with a newly diagnosed urologic malignancy, and thereby seems to have a clinical
      impact for many of our patients with urologic cancers.

PMID- 19576798
TI  - Despite the lack of association between different genotypes and the presence of
      prostate cancer, endothelial nitric oxide synthase a/b (eNOS4a/b) polymorphism
      may be associated with advanced clinical stage and bone metastasis.
AB  - OBJECTIVES: To investigate the relationship between the distribution of
      endothelial NO synthase (eNOS4a/b) gene polymorphism and clinical features of
      prostate cancer (PCa). METHODS AND MATERIALS: One hundred thirty-two patients
      with PCa (mean age 64.10 +/- 7.23 years) and 158 healthy controls (mean age 62.50
      +/- 7.53 years) with normal serum total prostate specific antigen (PSA) levels
      (<4 ng/ml) and digital rectal examinations (DRE) were enrolled in this
      prospectively designed study. PCa patients were classified as clinical T1 and T2
      stages (Group 1), clinical T3 and T4 stages without bone metastasis (Group 2),
      and patients with bone metastasis (Group 3). Genotypes (aa, bb, ab) for eNOS4a/b
      gene polymorphisms were identified by polymerase chain reaction analysis.
      Meanwhile, plasma nitrate and nitrite levels (NO(x)) were used to estimate the
      amounts of endogenous NO formation for both groups of patients. RESULTS: Despite
      lack of statistically significant differences between PCa patients and the
      control group in terms of distribution of genotypes and frequency of alleles,
      plasma NO(x) levels were found to be significantly increased in PCa patients
      compared with controls. Meanwhile, there was no significant difference between
      the group of PCa patients with high and low grade tumors (Gleason score >= 7 vs.
      < 7) in terms of genotype (aa + ab genotypes or a-allele vs. bb genotype)
      distribution. However, bb genotype was observed to be present at a higher
      frequency (85.1% vs. 60%) in Group 1; whereas a-allele was more frequent in Group
      2 (13.3% vs. 5.7%) and Group 3 (26.7 vs. 9.2). In addition, patients with a
      allele had a 3.79-fold risk of having advanced disease and bone metastasis in
      comparison with bb genotype. Moreover, multivariable logistic regression analysis
      revealed that eNOS4a/b polymorphism and plasma NOx levels were predictive factors
      for developing bone metastasis and high stage disease after adjustment for age
      and BMI. CONCLUSIONS: Our data did not reveal any relationship between any of
      these genotypes and the presence of PCa. However, the finding that PCa patients
      with bb genotype generally manifest localized disease and develop bone metastasis
      less frequently in comparison patients with a-allele may indicate an important
      role for this polymorphism in the molecular pathophysiology of PCa.

PMID- 19576799
TI  - Dual targeting of Bcl-2 and VEGF: a potential strategy to improve therapy for
      prostate cancer.
AB  - We previously demonstrated that Bcl-2 overexpression stimulates angiogenesis in
      PC-3 human prostate cancer cells, thus giving these tumors a growth advantage. To
      further elucidate the relationship between Bcl-2 and vascular endothelial growth
      factor (VEGF) in PC-3-Bcl-2 cells, tumorigenicity and angiogenesis were evaluated
      in our in vitro and in vivo model treated with antisense Bcl-2
      oligodeoxynucleotide (ASO) and bevacizumab. In vitro and in vivo angiogenesis
      assays, as well as a xenograft tumor model of the human prostate cancer cell line
      PC-3-Bcl-2, were subjected to ASO alone, bevacizumab alone, or the combination of
      ASO and bevacizumab. Protein-based assays (e.g., immunohistochemical staining and
      enzyme-linked immunosorbent assay [ELISA]) were utilized to detect molecular
      changes. Interestingly, targeting Bcl-2 with ASO resulted in the inhibition of in
      vitro tube formation and inhibition of angiogenesis in Matrigel plugs similar to
      treatment with bevacizumab. In our PC-3-Bcl-2 xenograft model, ASO alone resulted
      in 41% reduction in tumor size, bevacizumab alone resulted in a 50% reduction in
      tumor size, whereas the combination of ASO with bevacizumab was associated with
      >95% reduction in tumor volume. Reduction in tumor size in all groups was
      associated with reduction in Bcl-2 and VEGF expression, induction of apoptosis,
      and inhibition of angiogenesis and its associated chemokine production. These
      findings confirm that Bcl-2 is a pivotal target for cancer therapy and thus,
      further study of this novel combination of Bcl-2 reduction and angiogenic
      targeting in human tumors is warranted.

PMID- 19576800
TI  - A survey of therapy for advanced renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is very resistant to both chemotherapy and
      radiotherapy. Localized disease can be cured by surgery but most patients are
      diagnosed when distant metastases are already present and about 30% of patients
      relapse after nephrectomy. Until 2 years ago, cytokine-based immunotherapy
      (interleukin-2 and interferon-alpha) was the only therapeutic option for advanced
      RCC patients. Fewer than 20% of patients benefit from this treatment, but some of
      these may experience very prolonged complete responses and progression-free
      intervals, suggesting a possibility of cure in a very few cases. Thanks to our
      expanding knowledge of the biology and pathogenesis of RCC, the treatment of this
      disease has recently undergone a major advance, through the development of potent
      angiogenesis inhibitors and targeted agents. Bevacizumab, an antibody directed
      against vascular endothelial growth factor (VEGF), has shown significant activity
      in combination with interferon-alpha (IFN-alpha). Sunitinib and sorafenib,
      multikinase inhibitors with proven antiangiogenic activity, have also been
      approved for the treatment of this tumor. Finally, temsirolimus and everolimus,
      which belong to the family of mammalian target of rapamycin (mTOR), have shown
      some activity in selected patients. The aim of this paper is to review clinical
      trials with these new agents, describing their activity and profiles of toxicity,
      and to evaluate potential future developmental strategies.

PMID- 19576801
TI  - Robotic cystectomy and the Internet: separating fact from fiction.
AB  - INTRODUCTION: Patients commonly use the Internet to acquire health information.
      While a large amount of health-related information is available, the accuracy is
      highly variable. We sought to evaluate the current web-based information that
      exists with regard to robotic cystectomy. METHODS: Two common search engines
      (Google and Yahoo) were used to search the term "robotic cystectomy" and obtain
      the top 50 websites for each. These 100 sites were analyzed with regard to type
      of site, presence and accuracy of information on bladder cancer, and of
      information related to robotic cystectomy outcomes (surgical/oncologic,
      functional, and recovery). In addition, information taken from Intuitive Corp
      website was identified, as was the presence (or absence) and literature-based
      references. RESULTS: Of the 100 sites, 61 were surgeon/provider sites, 23 links
      to articles, 8 news stories, 3 patient support sites, 3 meeting program, and 2
      were the Intuitive site. Analysis of all 61 provider sites showed that 13%
      provided factually accurate information, 7% had both factual and erroneous
      information, and 80% had no information on bladder cancer. With regard to the
      purported benefits and outcomes of the robotic approach, a significant number of
      the sites had nonevidence-based claims with regard surgical/oncologic aspects
      (54%), functional recovery (26%), and surgical recovery (47%). Information taken
      directly from the Intuitive site was found on 33% sites, with 16% sites having a
      direct link. Only 4 provider sites (7%) had listed any references. CONCLUSIONS:
      These findings suggest that surgeons provide the majority of Internet information
      but do not often present evidence-based information and often over-state claims
      and outcomes of the robotic approach. This highlights the need for providers to
      deliver factual and evidence-based information to the public, and not suggest
      untrue/unproven claims that seem to presently occur.

PMID- 19576802
TI  - Complete remission achieved with angiogenic therapy in metastatic renal cell
      carcinoma including surgical intervention.
AB  - BACKGROUND: Former systemic therapy for metastatic renal cell cancer (mRCC) based
      on immunomodulation could achieve complete remissions (CR) in only some patients.
      Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the
      paradigm of treating mRCC based on a doubled progression-free survival (PFS) and
      10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is
      rarely seen. Within our patients we could achieve some CR, which we are
      presenting in this study. PATIENTS AND METHODS: We assessed 194 consecutive
      patients of an institutional database that were treated for mRCC with either
      sorafenib or sunitinib between 05/2006 and 12/2007. Restaging with repeated high
      resolution computed tomography (CT) of thorax and abdomen was performed in an 8
      to 10 weeks interval. Five patients who achieved CR in repeated CT under therapy
      are included in this analysis. RESULTS: Of the patients in whom we achieved CR,
      two were female and three were male. Median age was 63.2 years (range 52-70). All
      patients had clear cell histology. In three of the five patients, CR was achieved
      by surgery after partial remission, and in two patients it was achieved by sole
      medical therapy. All patients remained in CR until now with a median duration of
      CR of 24 months (range 24-29 months). One patient still is on therapy, while four
      patients do not receive any systemic treatment. CONCLUSIONS: We proof long-term
      confirmed CR in mRCC achieved by anti-angiogenic therapy alone or in combination
      with surgery. Combining surgery and anti-angiogenic therapy based on sorafenib
      and sunitinib could render patients free of disease even after repeated cycles of
      systemic treatment.

PMID- 19576803
TI  - The importance of anatomical suitability and fitness for the outcome of
      endovascular repair of ruptured abdominal aortic aneurysm.
AB  - INTRODUCTION: Endovascular repair of aortic aneurysm (EVAR) has a lower mortality
      than open repair. The aim of this study was to assess mortality from EVAR for
      emergency AAA repair and the impact of fitness for operation and adverse anatomy.
      METHODS: One-hundred and forty two patients who had EVAR for a ruptured AAA (80,
      REVAR) or a symptomatic AAA (62, SEVAR) between 1994 and 2007 in a single
      specialist endovascular centre were reviewed. Fitness for surgery was assessed by
      Hardman's index (age>76, loss of consciousness, Hb<9.0, Cr>190, ischaemic ECG).
      CT scans were reviewed, compared with operative images and operation notes for
      adverse anatomy. Details of perioperative complications, and outcome were
      recorded. RESULTS: Overall mortality at 24-h, 30-days and one year were,
      respectively: 17%, 36%, 50% for REVAR and 5%, 8%, 23% for SEVAR. Overall adverse
      anatomy increased 30-day mortality. Hardman's index of three or more increased
      mortality HR=2.59 (1.24-5.41), p=0.01. On Cox regression Univariate analysis
      increasing Hardman's index score and adverse anatomy increased the overall
      mortality over time. In multivariate Cox regression analysis (controlled for the
      Hardman's index) adverse anatomy was associated with significant increase in
      graft related mortality. CONCLUSION: The use of EVAR is feasible in patients who
      present with a ruptured or acutely symptomatic AAA. Care must be taken not to
      extend anatomical or clinical guidelines.

PMID- 19576804
TI  - Smear layer removal with passive ultrasonic irrigation and the NaviTip FX: a
      scanning electron microscopic study.
AB  - OBJECTIVE: The aim of this study was to compare the effect of continuous,
      intermittent passive ultrasonic irrigation (PUI) and active scrubbing of
      irrigants with NaviTip FX (Ultradent, South Jordan, UT) in removing smear layer.
      STUDY DESIGN: Forty single-rooted teeth were randomly divided into 5 test groups
      and subjected to final irrigation with 17% EDTA followed by 2.5% NaOCl for 1
      minute each using different activation methods: no activation (control), brushing
      with NaviTip FX, continuous PUI with irrigant delivered at pulp chamber,
      continuous PUI with irrigant delivered through the ultrasonic unit, and
      intermittent PUI. Specimens were examined under scanning electron microscope, and
      the data were analyzed using Friedman 2-way analysis of variance, Kruskal-Wallis,
      and Mann-Whitney U tests. RESULTS: NaviTip FX and intermittent PUI showed
      significantly lower smear score than other groups at the 3 mm level (P < .05).
      CONCLUSIONS: Both brush and intermittent ultrasonic activation were effective in
      the removal of smear layer from the apical third.

PMID- 19576806
TI  - Homogeneity and adaptation of endodontic fillings in root canals with enlarged
      apical preparation.
AB  - OBJECTIVE: The aim was to compare the homogeneity and adaptation of endodontic
      fillings placed in root canals with wide apical preparation. STUDY DESIGN: One
      hundred twenty root canals were prepared under simulated clinical conditions. The
      range of apical preparation size was 45 (narrow canals) to 60 (wide canals). The
      canals were filled using 4 techniques: Thermafil, GuttaFlow, apical cone, and
      vertical compaction. The root canals were sectioned at 5 levels. The adaptation
      and homogeneity of the filling were evaluated and statistically analyzed.
      RESULTS: The percentage of canal outline in contact with the filling in the
      Thermafil group (91.3% [95% confidence interval (CI) 88.8%-93.6%]) was
      statistically significantly lower than in the other groups. No statistically
      significant differences were found between GuttaFlow (96.6% [95% CI 95.7%
      97.5%]), apical cone (98.6% [95% CI 98.0%-99.3%]), and vertical compaction (98.1%
      [95% CI 96.5%-99.7%]). Similarly, the percentage of void area in Thermafil group
      (4.0% [95% CI 2.6%-5.3%]) was statistically significantly higher than in the
      other groups (GuttaFlow 1.4% [95% CI 0.1%-1.8%], apical cone 1.6% [95% CI 0.7%
      2.4%], and vertical compaction 0.1% [95% CI 0.1%-1.8%]). CONCLUSIONS: The tested
      filling techniques/materials provided similar high values for the homogeneity and
      adaptation to root canal walls after enlarged apical preparation, except for
      Thermafil at the most apical level.

PMID- 19576805
TI  - Myomucosal cheek flaps: applications in intraoral reconstruction using three
      different techniques.
AB  - OBJECTIVE: The use of myomucosal flaps harvested from the cheek area for
      intraoral reconstruction has been recently popularized in the literature. Several
      surgical techniques have been reported, and each study has described the outcomes
      and advantages of each method. However, the literature lacks a summary of the
      various surgical techniques utilizing buccinator myomucosal flaps. This paper
      examines the use of the 3 most important buccinator myomucosal flaps: the
      buccinator musculomucosal flap, the facial artery musculomucosal flap, and the
      buccinator musculomucosal island flap. We clarify the applications of each
      technique in intraoral reconstruction and discuss the indications for, and
      advantages and disadvantages of, each flap. STUDY DESIGN: Forty-six patients who
      underwent surgical resection for malignancies of the oral cavity and
      reconstructions with cheek flaps were retrospectively studied. RESULTS: All flaps
      were harvested and transposed. Complete loss of the flap occurred in only 1 case.
      In 2 cases, marginal necrosis of the flap took place, with complete spontaneous
      healing in 2 weeks. CONCLUSION: Buccinator musculomucosal flaps are a good option
      for reconstruction of moderately sized oral cavity defects. A key point in this
      procedure is flap selection based on not only the size and site of the defect,
      but also the patient's characteristics and type of surgical procedure.

PMID- 19576807
TI  - Epidermoid cyst of the clitoris: an unusual cause of clitoromegaly in a patient
      without history of previous female circumcision.
AB  - STUDY OBJECTIVE: To describe a rare cause of clitoromegaly. SETTING: University
      Medical Center. PARTICIPANTS: Patient. INTERVENTION: Magnetic resonance imaging,
      surgical resection of the cyst, clitoroplasty. RESULTS: Clitoroplasty with
      removal of the intradermal cyst and resolution of pain. CONCLUSIONS: A 17-year
      old immigrant female presented with clitoral pain associated with clitoromegaly.
      Epidermoid cysts are usually solitary, asymptomatic, slow-growing, proliferations
      of epidermal cells that are commonly present on the neck, scalp, face, or trunk.
      There have only been four reported cases of epidermoid cysts of the clitoris not
      associated with female genital mutilation. The cyst in this case was removed by
      local excision, and the patient's pain has resolved.

PMID- 19576808
TI  - Successful pregnancy following surgery in the obstructed uterus in a uterus
      didelphys with unilateral distal vaginal agenesis and ipsilateral renal agenesis:
      case report and literature review.
AB  - SYNOPSIS: After surgical correction of unilateral distal vaginal agenesis, the
      obstructed didelphic uterus was able to harbor 2 subsequent pregnancies.
      BACKGROUND: There was a congenital anomaly syndrome of uterus didelphys,
      unilateral distal vaginal aplasia, and ipsilateral renal aplasia. Intuition
      suggests that later pregnancy would be in the unobstructed uterus. OBJECTIVE: The
      purpose is to report pregnancy occurring twice in a previously obstructed
      didelphic uterus after surgical correction. CASE: A girl aged 13 years, 8 months
      presented with the syndrome of didelphic uterus, upper right hematocolpos, and
      right renal aplasia. Right vaginal marsupialization was done. Subsequently, she
      had 2 pregnancies in the right didelphic uterus. CONCLUSION: Pregnancy occurred
      in the obstructed uterus despite a large hematometra, extensive right pelvic
      peritoneal endometriosis, and hematocolpos. The surgeon should make every effort
      to preserve the obstructed uterus.

PMID- 19576809
TI  - Virilizing luteinized thecoma of the ovary in a 15-year-old female: a case
      report.
AB  - BACKGROUND: Only 30% of luteinized thecomas are found in women under the age of
      30, and they are typically benign. Only 11% of luteinized thecomas show clinical
      signs of androgen production. We present an unusual case of a 15-year-old female
      who presented with secondary amenorrhea and virilization and was subsequently
      diagnosed with a benign luteinized thecoma of the ovary. This is the youngest
      nonmalignant luteinized thecoma reported to date. CASE: A 15-year-old Sri Lankan
      female presented with increasing hair growth, a hoarse voice, and secondary
      amenorrhea. On physical examination, there was marked hirsutism and
      clitoromegaly. Investigations found an elevated free testosterone level and an
      enlarged, homogenous left ovary with absent normal ovarian architecture. A
      laparotomy and unilateral salpingo-oophorectomy was performed. The final
      diagnosis was a luteinized ovarian thecoma, with no evidence of malignancy.
      Postoperatively, testosterone levels normalized and menstrual cycles resumed.
      Although laser treatment helped with her hirsutism, her other virilizing symptoms
      (deepening of voice, clitoromegaly) did not improve postoperatively. CONCLUSION:
      This case of a virilizing ovarian luteinized thecoma emphasizes the need for
      timely evaluation, diagnosis, and treatment of patients presenting with symptoms
      of excess androgen secretion in order to avoid irreversible unwanted effects.
      Possible ovarian causes of excess androgen secretion should not be overlooked
      when considering possible causes of hyperandrogenism and secondary amenorrhea.

PMID- 19576810
TI  - Vaginal burn injury due to alkaline batteries.
AB  - BACKGROUND: Alkaline batteries are known to cause caustic burns to the esophagus
      when ingested. We report a case of alkaline burns to the vagina. CASE: A 13-year
      old female presented to the Emergency Department with abdominal pain. She was
      admitted for necrotic vaginal burns after batteries were removed from her vagina.
      Examination under anesthesia revealed multiple third degree burns without
      perforation into adjoining structures. Management included topical estrogen,
      topical antibiotic, and an oral nonsteroidal anti-inflammatory. She was re
      examined under anesthesia at 5 days, then weekly as an outpatient. Follow-up
      examinations at 5 and 36 months later confirmed complete healing. CONCLUSION: In
      this unique case, we discuss the treatment options and postulate reasons for the
      excellent outcome in this patient.

PMID- 19576811
TI  - Hemangioma of the clitoris presenting as clitoromegaly: a case report.
AB  - A 20-year-old woman with massive clitoral enlargement is presented to discuss the
      differential diagnosis and the treatment of this condition.

PMID- 19576812
TI  - A diagnostic dilemma: functioning noncommunicating uterine horn and elevated
      levels of CA125.
AB  - BACKGROUND: Mullerian duct abnormalities are important to diagnose, considering
      the various clinical manifestations, implications for reproductive life,
      different treatment options, and prognoses. However, they are often difficult to
      diagnose, especially by noninvasive means. Here we discuss the diagnostic
      difficulty incurred in a case of unicornuate uterus with functioning
      noncommunicating horn having a high level of cancer antigen 125 as a presenting
      feature. CASE: Unicornuate uterus with raised serum CA125. CONCLUSIONS: Mullerian
      duct anomaly can be a differential diagnosis in women with adnexal mass and
      elevated CA125.

PMID- 19576813
TI  - Spontaneous rupture of benign ovarian cystic teratoma in a premenarcheal girl.
AB  - BACKGROUND: Spontaneous rupture of benign cystic ovarian teratoma is an unusual
      occurrence. CASE: A 9-year-old girl presented with acute onset of abdominal pain.
      Under a radiological diagnosis of cystic ovarian teratoma, she underwent
      laparoscopic cystectomy, preserving as much ovarian tissue as possible. Direct
      observation of a defect on the tumor surface and the presence of keratinized
      squamous cells in the ascites were important clues for intraperitoneal rupture.
      Pathologically, the defect was surrounded by inflamed tissues adjacent to the
      gastric mucosa, suggesting that autolysis of the wall by proteolytic enzymes
      induced the spontaneous rupture. SUMMARY AND CONCLUSION: We present the youngest
      and first premenarcheal case of spontaneous rupture of cystic ovarian teratoma.
      Early diagnosis and minimally invasive surgical procedure are essential to
      preserve future fertility.

PMID- 19576814
TI  - Massive ovarian edema and contralateral mature cystic teratoma: asymptomatic
      presentation in a premenarchal female.
AB  - BACKGROUND: Massive ovarian edema is a rare entity, which in most cases occurs in
      adult females presenting with abdominal pain. We present an unusual case
      associated with contralateral teratoma in a premenarchal female. CASE: A 13-year
      old asymptomatic female presenting with an abdominopelvic mass was referred to
      the gynecological oncology unit with complex bilateral pelvic masses seen on
      ultrasound. A combination of computed tomography and repeat ultrasound
      demonstrated a solid mass containing numerous subcentimeter cysts inseparable
      from a mature teratoma. Exploratory surgery resulted in unilateral oophorectomy
      and contralateral cystectomy. Pathology confirmed massive ovarian edema and
      contralateral mature teratoma. SUMMARY AND CONCLUSION: Recognition of this rare
      condition is important to avoid overtreatment of massive ovarian edema.
      Intraoperative biopsy is recommended as an alternative to oophorectomy in this
      patient group.

PMID- 19576815
TI  - Uterus didelphys and longitudinal vaginal septum coincident with an obstructive
      transverse vaginal septum.
AB  - A wide variety of Mullerian anomalies has been described in the literature.
      Various combinations of anomalies may coexist in a single subject. Precise
      identification of the various components of the anomaly is paramount in choosing
      and planning the appropriate conservative and surgical treatment. In this report,
      we present a rare case of combined vertical fusion and transverse canalization
      defects in a single subject. A review of the literature along with an overview of
      the pertinent embryologic processes and management concepts for such cases are
      presented.

PMID- 19576816
TI  - Diagnosis of Trichomonas vaginalis in female children and adolescents evaluated
      for possible sexual abuse: a comparison of the InPouch TV culture method and wet
      mount microscopy.
AB  - STUDY OBJECTIVE: To compare the performance of wet mount microscopy and the
      InPouch TV culture method in diagnosing Trichomonas vaginalis in a cohort of
      female children and adolescents evaluated for possible sexual abuse. DESIGN: A
      prospective study in which samples for both wet mount and InPouch TV were
      collected from the vaginal vault of each participant. The wet mount was examined
      microscopically for the presence of motile trichomonads, and the InPouch TV was
      analyzed in accordance with manufacturer specifications. SETTING: A regional,
      university-affiliated sexual abuse center in Nashville, TN. PARTICIPANTS: Females
      (N = 271) aged 10 to 17 years (inclusive) who met screening criteria for sexually
      transmitted infection testing in accordance with Centers for Disease Control
      recommendations, and who exhibited evidence of at least partial hymenal
      estrogenization. MAIN OUTCOME MEASURES: A Trichomonas vaginalis diagnosis either
      via detection of motile trichomonads on wet mount or a positive InPouch TV.
      RESULTS: The median age of the 271 participants was 13.6 years, 88% (235/268)
      were genital Tanner stage 4 or 5, and 66% (173/263) were Caucasian. Trichomonas
      vaginalis was diagnosed by either wet mount or InPouch TV in 4% (12/274) of the
      possible sexually transmitted infection exposures. The sensitivity of wet mount
      was 8/12 = 0.67 (95% confidence interval [CI]: 0.39, 0.86) and specificity was
      262/262 = 1.00 (95% CI: 0.99, 1.00). The false negative rate of wet mount was
      4/12 = 0.33 (95% CI: 0.14, 0.61). CONCLUSIONS: A culture-based method such as
      InPouch TV should be considered for Trichomonas vaginalis diagnosis when
      evaluating children and adolescents in whom sexual abuse is a concern.

PMID- 19576817
TI  - The prevalence of abnormal liver enzymes and metabolic syndrome in obese
      adolescent females with polycystic ovary syndrome.
AB  - OBJECTIVES: We sought to determine the prevalence of abnormal liver enzymes
      suggestive of nonalcoholic steatohepatitis and metabolic syndrome in obese
      adolescent females with polycystic ovary syndrome. DESIGN: A retrospective chart
      review. PARTICIPANTS: Patients included 39 obese (body mass index Z score >/= 2)
      adolescent females with a diagnosis of polycystic ovary syndrome. Clinical and
      biochemical data in these patients were reviewed. MAIN OUTCOME MEASURES:
      Aspartate and alanine aminotransferase levels, lipid panel, blood pressure, body
      mass index, and glucose intolerance were the main outcome measures of the study.
      RESULTS: The study showed that 15.4 % (6 of 39) of patients had elevated
      aminotransferase levels, suggestive of nonalcoholic steatohepatitis, and 43.6 %
      (17 of 39) of patients qualified as having metabolic syndrome. Finally, 10.2 % (4
      of 39) of patients were found to have both liver dysfunction and metabolic
      syndrome. CONCLUSION: Liver dysfunction consistent with nonalcoholic
      steatohepatitis and metabolic syndrome are prevalent in obese adolescent females
      with polycystic ovary syndrome. Therefore, early screening and further work-up
      for both disease states are warranted in cases of young adolescent females with
      polycystic ovary syndrome.

PMID- 19576818
TI  - Reproductive health in Nigeria.
AB  - BACKGROUND: Adolescents have special reproductive health needs, but these
      peculiar needs are often unmet in many cultures and countries. METHODS: A cross
      sectional study involving adolescents in three secondary schools in a northern
      Nigerian setting. Demographic characteristics as well as reproductive health
      issues (adolescent sex, abortion, sexual experience) among the students were
      surveyed. RESULTS: Of the 1070 students that fully participated in the survey,
      539 (50.4%) were girls and 531 (49.6%) boys. They were aged 10 - 27 years (median
      16 Years). Five hundred forty three (50.7%) were Christians and 499 (46.6%)
      Muslims. Nine hundred and four (84.5%) of the students knew about abortion. On
      their view about reasons why adolescents indulge in premarital sex, 574 (53.6%)
      felt it was to please boyfriend/girlfriend, 391 (36.5%) to experiment with sex,
      312 (29.6%) to test fertility and 239 (22.3%) felt it was to stop painful
      menstruation. One hundred thirty five (12.6%) have had sex and 15 - 19 years age
      group were more likely to be sexually active. Twelve (1.1%) of the girls had been
      pregnant once - four times before and all had an abortion. Children of civil
      servants were significantly more likely to be sexually active compared to other
      groups of children (p <0.05). All the respondents knew one or more complication
      of abortion to include inability to get pregnant in future 682 (63.7%), abdominal
      pain 589 (55%) and painful menstruation 427 (39.9%). CONCLUSION: Adolescents are
      unique in every way including issues of reproductive health. The age at sexual
      debut in this setting is early. There is a need to include reproductive health
      education in the curriculum of secondary schools. This should help the
      adolescents to obtain the correct information from the right source.

PMID- 19576819
TI  - Vaginal voiding: a common cause of daytime urinary leakage in girls.
AB  - STUDY OBJECTIVE: To estimate the frequency of vaginal voiding as the cause of
      daytime urinary leakage in girls, and to study the effect of instructions
      intended to alleviate the problem. SETTING: Girls with vaginal voiding were
      identified in a group of girls referred because of daytime urinary leakage. They
      were evaluated by a noninvasive screening protocol. Girls with vaginal voiding
      were instructed on how to achieve better toilet habits. PARTICIPANTS: Twelve
      girls with vaginal voiding. RESULTS: Vaginal voiding was found in 12 of 39 girls
      with daytime urinary leakage. Their age ranged between 8.5 and 13.9 years. They
      all had history of small leakage immediately after voiding. A body mass index
      greater than the corresponding 85th percentile was noted in 5 girls, and labial
      fusion was noted in 2 girls. The complaint disappeared in 10 girls and improved
      in the remaining 2 girls after instructions on how to achieve better toilet
      habits. CONCLUSIONS: Vaginal voiding is common in girls. It occurs in girls at
      risk of overweight, in girls with labial fusion, and in girls adopting a hairpin
      posture while sitting on the toilet. The diagnosis is obtained by an adequate
      history. Proper voiding instructions resolve the problem.

PMID- 19576820
TI  - Juvenile granulosa cell ovarian tumor: a case report and review of literature.
AB  - BACKGROUND: Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that
      frequently present with precocious puberty. Presentation in infants less than a
      year of age is also rare. CASE: We describe a 10-month-old infant who presented
      with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation
      revealed classic elevation of estradiol and inhibin B, and less classic elevation
      of total and free testosterone. Oophorectomy and staging resulted in a diagnosis
      of Stage IA JGCT. SUMMARY AND CONCLUSION: Survival rates are >95% among patients
      diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late
      as 48 months. Therefore, tumor surveillance is warranted for patients with even a
      Stage IA JGCT and involves monitoring serial inhibin B levels along with
      intermittent imaging.

PMID- 19576821
TI  - Genital prolapse in a newborn following resection of sacrococcygeal teratoma.
AB  - Neonatal genital prolapse usually occurs during the first few days of life and
      presents as a tumor mass protruding from the vulva. We present a 15-day-old
      female neonate who developed neonatal genital prolapse following the operation of
      sacral teratoma. We suggest that sacral teratoma operation may be a significant
      predisposing factor for genital prolapse in neonates and the neonatal vaginal
      prolapse may be one of the differential diagnoses of interlabial mass during the
      late neonatal period.

PMID- 19576822
TI  - Practice variation in screening for sexually transmitted infections with nucleic
      acid amplification tests during prepubertal sexual abuse evaluations.
AB  - BACKGROUND: Although recent recommendations for children after suspected sexual
      abuse incorporate nucleic acid amplification tests (NAATs) in algorithms that
      detect sexually transmitted infections (STIs), screening practices in the
      community remain uncertain. STUDY OBJECTIVE: We examined screening practices over
      time and across a variety of pediatric settings for the evaluation of STIs in
      sexually abused children. METHODS: A consecutive cohort of prepubertal children
      younger than 11 years of age who were suspected to have been sexually abused were
      identified between May 2002 and April 2005 at a large tertiary children's
      hospital and its supporting primary care network. Detailed histories and
      examinations based on chart abstraction were linked to hospital laboratory
      records to identify those who were screened for Chlamydia trachomatis and
      Neisseria gonorrhoeae by means of cultures, NAATs, or both. Chi-square and
      logistic regression analyses identified factors associated with screening,
      including the effects of screening location and year of study on the likelihood
      that particular tests were obtained. RESULTS: Among the initial visits of 1068
      children, 32% occurred in the specialty child abuse clinic (CARE Clinic), 62% in
      the emergency department, and 6% in the primary care setting. Follow-up visits
      occurred in only 7% of children. The performance of at least one screening test
      increased each year, from 12% in year 1 to 18% in year 3 (P = 0.01). Among the
      162 children in whom tests were obtained, there was a significant decrease in the
      use of culture techniques over time, from 100% in year 1 to 75% in year 3 (P <
      0.001). At the same time, there was a steady increase in the use of NAATs in
      total (from 2% in year 1 to 41% in year 3, P < 0.001), and in the absence of
      culture techniques (from 0% in year 1 to 26% in year 3, P < 0.001). This growth
      in the use of NAATs alone was particularly seen in the emergency department
      setting, where 33% of children were screened only by NAAT by year 3 (P = 0.001).
      CONCLUSIONS: Screening rates for STIs increased over time, a trend that is
      explained primarily by the use of NAATs in the absence of other tests. The
      increasing use of NAATs will have to be addressed more fully in creating future
      guidelines for this population.

PMID- 19576823
TI  - Hair-thread tourniquet syndrome of labia minor.
AB  - BACKGROUND: Several organs may be damaged by strangulation by hair or strings
      that cause ischemia and necrosis. There have been sporadic case reports of such
      events. Injuries to the hands, feet, and fingers, as well as penile(1-5) and
      clitoral injuries(6-8) have been reported. CASES: Three cases of labia minor
      strangulation by hair are described. A review of the relevant literature is
      included. CONCLUSIONS: Pediatricians, gynecologists, and family physicians must
      be aware of labial tourniquet syndrome. If the diagnosis is missed or remains
      without immediate attention, the hair or string may cause necrosis and the
      resulting amputation of the vital body part.

PMID- 19576824
TI  - Vaginal laceration as a result of blunt vehicular trauma.
AB  - BACKGROUND: Sexual abuse often is the primary diagnosis considered when
      prepubertal girls present with vaginal trauma. Although sexual abuse is very
      concerning and should remain high in the differential diagnosis, a variety of
      accidental injuries also can cause genital injury. CASE: A 5-year-old girl
      presented to the emergency department with genital bleeding after a vehicle
      rolled over her pelvis. She had isolated vaginal lacerations on exam. SUMMARY AND
      CONCLUSION: Extreme pelvic compression is an adequate mechanism of injury in a
      child presenting with vaginal laceration.

PMID- 19576825
TI  - Multicenter study of knowledge about human papilloma virus and attitudes among
      emergency department patients.
AB  - STUDY OBJECTIVE: We sought to evaluate knowledge of human papilloma virus (HPV)
      and attitudes toward the HPV vaccine among emergency department (ED) patients.
      DESIGN: Cross-sectional survey. SETTING: Three Boston EDs. PARTICIPANTS: We
      enrolled consecutive patients during two 24-hour periods at each site.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Knowledge of HPV and attitudes toward
      the HPV vaccine. RESULTS: We enrolled 387 patients (81% of eligible). Overall,
      242 (63%) participants had heard of HPV and 203 (52%) supported state-mandated
      vaccination. In the multivariate model, characteristics associated with lower
      awareness of HPV were: (1) older age (compared to age 18 - 26-years: OR 0.45
      [95%CI, 0.20-0.99] for age 27-44 years, OR 0.26 [95%CI, 0.12-0.56] for age 45-64
      years, and OR 0.10 [95%CI, 0.04-0.28] for age 65 year or older), (2) black race
      (compared to white: OR 0.31 [95%CI, 0.15-0.64]); and (3) lower annual household
      income (OR 0.39 [95%CI, 0.19-0.81] for $40,000 or less). Of those people who had
      heard of HPV, 82% knew of its relationship to cervical cancer, but only 61%
      thought it was a sexually transmitted disease (STD). Support for state-mandated
      vaccination was higher among participants who knew that HPV was an STD (OR 2.9
      [95%CI 1.7-5.0]), but was not higher among those who had heard of HPV (OR 0.64
      [95%CI 0.34-1.2]) or who knew that HPV causes cervical cancer (OR 0.85 [95%CI
      0.45-1.6]). CONCLUSIONS: Support for state-mandated HPV vaccination appears to be
      driven more by the knowledge that HPV is an STD than by its role in cervical
      cancer. Awareness that HPV is transmitted through sexual activity does not
      decrease support for vaccination and may actually enhance it.

PMID- 19576826
TI  - Use of misoprostol for management of unsatisfactory colposcopy in the adolescent:
      a case report and review of the literature.
AB  - STUDY OBJECTIVE: To document the ability to use a prostaglandin analogue to
      achieve satisfactory colposcopy in a patient with cervical stenosis and
      unsatisfactory colposcopy. DESIGN: Case report. RESULTS: Satisfactory colposcopy
      was achieved by using 100mg of Misoprostol orally, administered the night before
      the planned colposcopic evaluation. CONCLUSION: In the presence of persistent
      atypia in an adolescent female with an unsatisfactory colposcopy, consider using
      a prostaglandin analogue for adequate evaluation of the endocervix, prior to
      proceeding with an ablative or excisional therapy.

PMID- 19576827
TI  - Risk factors for epilepsy in children with cerebral palsy.
AB  - The purpose of the study was to identify predictive risk factors for epilepsy
      among children with cerebral palsy. We conducted a retrospective study of the
      clinical characteristics of children with cerebral palsy and epilepsy in
      comparison to those of children with cerebral palsy without epilepsy. The
      examined parameters included: the prevalence and the age of onset of the
      seizures, the clinical subgroup of cerebral palsy and subtype of epileptic
      seizures. We looked for possible risk factors including the presence of neonatal
      seizures, the imaging findings, the gestational age at delivery, the adjusted
      birth weight, the mode of delivery, the Apgar scores, and the head size as well
      as the presence of consanguinity. Epilepsy occurred in 33% of the studied
      children. Almost 50% of the epileptic children had their first seizure within the
      first 12 months of life. Neonatal seizures were strong predictors for epilepsy
      (p<0.001). Presence of at least one abnormal structural finding (particularly
      brain atrophy) was also a significant predictor of epilepsy (p<0.003). Low Apgar
      score at 5 min after birth and birth at term were also found more frequently
      among patients with epilepsy, although when adjusted with other risk factors,
      Apgar score did not reach statistical significance. The mode of delivery, head
      circumference, adjusted birth weight, gender and ethnic group, consanguineous
      marriage and prematurity were not found to be risk factors for the occurrence of
      epilepsy in these children.

PMID- 19576828
TI  - Dielectric inserts for sensitivity and RF magnetic field enhancement in NMR
      volume coils.
AB  - A method for enhancing the signal to noise ratio (SNR) in NMR volume coils is
      described. By introducing inserts made of low-loss, high dielectric constant
      material into specific locations in the coil, the SNR can often be enhanced by up
      to 20%, while B(1) homogeneity is hardly affected. A model for predicting the
      limit of the SNR improvement is also presented. The model accurately predicts the
      SNR gain obtained in both numerical simulations and experiment. An experiment was
      conducted on a mini-MRI system. Experimental results are in very good agreement
      with the simulations in regard to both SNR improvement and B(1) enhancement in
      transmission. Inserts made of ultra high dielectric constant materials can be as
      thin as few millimeters, thus, conveniently fitting into existing coil-sample
      gaps in volume coils.

PMID- 19576829
TI  - Impact of selective excitation on carbon longitudinal relaxation: Towards fast
      solid-state NMR techniques.
AB  - The effect of selective pulses on the apparent carbon longitudinal relaxation is
      investigated in three fully (13)C-labeled systems, histidine as a model system
      and two proteins MerP and YajG. It is shown that the longitudinal relaxation of a
      selectively excited carbon spin is greatly enhanced, mainly because of fast spin
      diffusion. This relaxation enhancement allows reducing the time necessary for
      polarization recovery between two experiments. This effect can be exploited
      either to improve the sensitivity of NMR experiments or to reduce the
      experimental time. Using selective carbon excitation combined with fast pulsing
      on fully (13)C-labeled proteins, a sensitivity improvement of 20-45% over
      standard cross-polarization methods is predicted from the measured relaxation
      times.

PMID- 19576830
TI  - Prevalence of apoptotic epidermal keratinocytes in eosinophilic dermatoses of the
      cat: a retrospective light-microscopic study of 145 skin-biopsy specimens.
AB  - A retrospective light-microscopic study was performed on skin-biopsy specimens
      from 145 cats with eosinophilic inflammatory dermatoses in order to determine the
      prevalence of apoptotic epidermal keratinocytes (AKs), the prevalence of
      eosinophils in close proximity to AKs, and whether there was a difference in the
      prevalence of AKs or the prevalence of eosinophils in close proximity to AKs
      based on histopathological reaction pattern. Overall, 62/145 (43%) specimens had
      AKs. Of the cases in which AKs were seen, 18% had eosinophils in close proximity
      to the AKs. The specimens were divided into three groups based on
      histopathological reaction pattern: perivascular-to-interstitial, diffuse, and
      nodular. No difference in the prevalence of AKs was found among the three
      histological groups. Because the sample size containing eosinophils in close
      proximity to AKs was too small to compare the three histological patterns
      individually, nodular and non-nodular patterns were compared. No difference in
      the presence of eosinophils in close proximity to AKs was found in these two
      subsets. More AKs were present if eosinophils were in close proximity to the AKs
      (range 1-9 with eosinophils near compared to 0-7 without).

PMID- 19576831
TI  - Bilateral laparoscopic subtotal perinephric pseudocyst resection in a cat.
AB  - A 17-year-old castrated male domestic shorthair cat was diagnosed with bilateral
      perinephric pseudocysts (PNPs). Bilateral subtotal resection of the PNPs was
      performed via a laparoscopic approach. There was no regrowth or reformation of
      the PNPs after the procedure and the cat's serum concentration of creatinine
      remained stable for 6 months after surgery. Laparoscopic bilateral subtotal
      resection of PNPs appears to have been an effective treatment option in this cat
      with the advantages of being minimally invasive and requiring only a brief
      hospital stay.

PMID- 19576832
TI  - Low-grade alimentary lymphoma: clinicopathological findings and response to
      treatment in 17 cases.
AB  - Low-grade alimentary lymphoma (LGAL) was diagnosed by histological and
      immunohistochemical evaluation of full-thickness biopsies from multiple regions
      of the gastrointestinal tract collected during exploratory laparotomy in 17 cats.
      The most common clinical signs were weight loss (n=17) and vomiting and/or
      diarrhoea (n=15). Clinical signs were chronic in 11 cases. Abdominal palpation
      was abnormal in 12 cats, including diffuse intestinal thickening (n=8), an
      abdominal mass due to mesenteric lymph node enlargement (n=5) and a focal mural
      intestinal mass (n=1). The most common ultrasonographic finding was normal or
      increased intestinal wall thickness with preservation of layering. Ultrasound
      guided fine-needle aspirates of mesenteric lymph nodes (n=9) were incorrectly
      identified as benign lymphoid hyperplasia in eight cats, in which the
      histological diagnosis from biopsies was lymphoma. There was neoplastic
      infiltration of more than one anatomic region of the gastrointestinal tract in
      16/17 cats. The jejunum (15/15 cats) and ileum (13/14 cats), followed by the
      duodenum (10/12 cats), were the most frequently affected sites. Twelve cats were
      treated with oral prednisolone and high-dose pulse chlorambucil, two with a
      modified Madison-Wisconsin multiagent protocol and three with a combination of
      both protocols. Thirteen of the 17 cats (76%) had complete clinical remission
      with a median remission time of 18.9 months. Cats that achieved complete
      remission had significantly longer median survival times (19.3 months) than cats
      that did not achieve complete remission (n=4) (4.1 months; P=0.019). The
      prognosis for cats with LGAL treated with oral prednisolone in combination with
      high-dose pulse chlorambucil is good to excellent.

PMID- 19576833
TI  - Impact of patient setup error in the treatment of head and neck cancer with
      intensity modulated radiation therapy.
AB  - PURPOSE: To study the impact of setup errors on the dose to the target volume and
      critical structures in the treatment of cancer of nasopharynx with intensity
      modulated radiation therapy (IMRT). METHODS AND MATERIALS: Twelve patients of
      carcinoma of nasopharynx treated by IMRT with simultaneous integrated boost
      technique were enrolled. The gross tumor volume, clinical target volume and low
      risk nodal region were planned for 70, 59.4 and 54 Gy, respectively, in 33
      fractions. Based on the constraints, treatment plans were generated. Keeping it
      as the base plan, the patient setup error was simulated for 3, 5 and 10mm by
      shifting the isocenter in all three directions viz. anterior, posterior,
      superior, inferior, right and left lateral. The plans were evaluated for mean
      dose, maximum dose, volume of PTV receiving >110% and <93% of the prescribed
      dose. For both the parotids, the mean dose and the dose received by >50% of the
      parotid were evaluated. The maximum dose and dose received by 2 cc of spinal cord
      were also analyzed. RESULTS: The dose to the target volume decreases gradually
      with increase in setup error. The superior and inferior shifts play major role in
      tumor under-dosage. A setup error of 3mm along the posterior and lateral
      directions significantly affects the dose to the spinal cord. Similarly, setup
      error along lateral and anterior directions affects the dose to both parotids.
      CONCLUSIONS: The isocenter position should be verified regularly to ensure that
      the goal of IMRT is achieved.

PMID- 19576834
TI  - Presence, characterization, and genotype profiles of Mycobacterium avium
      subspecies paratuberculosis from unpasteurized individual and pooled milk,
      commercial pasteurized milk, and milk products in India by culture, PCR, and PCR
      REA methods.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's
      disease in ruminants, a chronic enteritis evocative of human inflammatory bowel
      disease. In industrialized countries MAP has been cultured from pasteurized milk,
      compounding the increasing concern that MAP may be zoonotic. The purpose of this
      study was to evaluate commercially available unpasteurized and pasteurized milk
      and its products for the presence of viable MAP or MAP DNA from an area of
      northern India with a population of 150 million people. METHODS: We studied 43
      samples (16 unpasteurized, 27 pasteurized) purchased in Mathura, Agra, or New
      Delhi, for the presence of MAP by culture or by PCR for IS900 MAP DNA. Positives
      results were confirmed as MAP by restriction endonuclease analysis and/or DNA
      sequencing. RESULTS: Colonies appeared in 1.5-20 months post-inoculation. Of the
      unpasteurized samples, 44% (7/16) were MAP culture-positive and 6% (1/16) were
      positive for IS900 MAP DNA. Of the pasteurized samples, 67% (18/27) were MAP
      culture-positive and 33% (9/27) were IS900-positive. Subsequently, 100% (25/25)
      of the cultured colonies were IS900 and IS1311 MAP DNA-positive. CONCLUSIONS:
      This is the first report from a developing country of MAP cultured from both
      pasteurized and unpasteurized milk and milk products. Thus we corroborate the
      presence of viable MAP in the food chain reported from industrialized countries.
      With the increasing concern that MAP may be zoonotic, these findings have major
      implications for healthcare in India. The decreased sensitivity in detecting MAP
      DNA by PCR directly from milk should be ascribed to our employing only one set of
      PCR primers.

PMID- 19576835
TI  - Cloxacillin-based therapy in severe septic bursitis: retrospective study of 82
      cases.
AB  - OBJECTIVE: The purpose of this retrospective study was to describe a tertiary
      care center experience with different antibiotic strategies that include
      cloxacillin (C) in patients with severe septic bursitis (SB). METHODS: A severe
      SB was considered when the patient needed hospitalization and/or intravenous
      (i.v.) antibiotics. Patients were treated with bursal aspiration and one of these
      antibiotic options: C, 2 g/4 h per day i.v. until improvement, and afterwards 1
      g/6 h per day v.o. until resolution; (C+G), gentamicin i.v. was added to C for 5
      to 7 days (initial dose 240 mg/d); (C+R), rifampicin was added at a dose of 600
      mg/d v.o. RESULTS: The study comprised 82 patients with severe SB. The mean delay
      to diagnosis was 6.1+/-6.9 days, and the most frequent location was the
      prepatellar bursa. In 67%, the bursal fluid culture yield a positive result,
      being Staphylococcus aureus the most frequent bacteria isolated (94.4%). At
      admission, fever and extensive cellulites were more frequent in the C+G group.
      Patients in the C+G had a longer duration of i.v. antibiotics compared with the C
      group (p=0.008), although the total duration of antibiotics was not different.
      There was a tendency in the C+R group to need more surgery. All patients except
      one had a complete resolution and there were no differences in side effects.
      CONCLUSION: In patients with severe SB without extensive cellulites i.v., C alone
      may be sufficient. In patients with a more severe presentation, C plus gentamicin
      seems to be an appropriate option in the majority of them.

PMID- 19576836
TI  - The effect of bone marrow mononuclear cells on vascularization and bone
      regeneration in steroid-induced osteonecrosis of the femoral head.
AB  - OBJECTIVE: We examined whether implantation of autologous bone marrow mononuclear
      cells (BM-MNC) can augment neovascularization and bone regeneration in steroid
      induced osteonecrosis of the femoral head. METHODS: Sixty-five 28-week-old male
      New Zealand white rabbits were divided into group I (left untreated, N=20), group
      II (core decompression, N=20) and group III (core decompression+autologous bone
      marrow cells implantation, N=25) after receiving an established inductive
      protocol for inducing steroid-associated ON. Four weeks later, these rabbits were
      euthanized, bilateral femora were dissected for micro-CT-based microangiography
      to assess vascularization, and then the osteonecrotic changes and repair
      processes were examined histopathologically. RESULTS: Quantitative analysis
      showed that new vessel formation in group III was significantly greater compared
      with other groups at 4 weeks after treatment. Penetrating capillary vessels
      number vessels number in group III (44.5+/-5.11) was significantly larger than
      that of group II (11.4+/-2.46) and group I (3.10+/-0.33) (p<0.01). The histologic
      and histomorphometric analysis revealed that the new bone volume was
      significantly higher in the group III than in the group I and II, 4 weeks after
      treatment. CONCLUSION: In this animal model, a combination of bone marrow
      mononuclear cells and core decompression enhance the neovascularization and the
      osteoinductive ability, resulting in bone regeneration. These findings confirm
      the preliminary clinical results obtained in humans that the implantation of bone
      marrow mononuclear cells is an effective and feasible method for treating early
      osteonecrosis.

PMID- 19576837
TI  - An enhanced two-step floating catchment area (E2SFCA) method for measuring
      spatial accessibility to primary care physicians.
AB  - This paper presents an enhancement of the two-step floating catchment area
      (2SFCA) method for measuring spatial accessibility, addressing the problem of
      uniform access within the catchment by applying weights to different travel time
      zones to account for distance decay. The enhancement is proved to be another
      special case of the gravity model. When applying this enhanced 2SFCA (E2SFCA) to
      measure the spatial access to primary care physicians in a study area in northern
      Illinois, we find that it reveals spatial accessibility pattern that is more
      consistent with intuition and delineates more spatially explicit health
      professional shortage areas. It is easy to implement in GIS and straightforward
      to interpret.

PMID- 19576838
TI  - Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and
      hypopharynx: prognostic impact may depend on type of treatment and stage of
      disease.
AB  - he purpose of this study was to evaluate the prognostic influence of various
      subtypes of tumour infiltrating lymphocytes (TIL) in head and neck cancer, in
      particular the potential influence of regulatory T cells (Treg) in relation to
      different treatment modalities was addressed. A total of 115 patients with
      squamous cell carcinoma of the oro- and hypopharynx were selected. A low-risk
      group of 62 patients with early disease was treated by primary surgery followed
      by external radiotherapy. A high-risk group of 53 inoperable patients with
      advanced disease was treated by primary radiochemotherapy. Two-hundred and forty
      biopsy samples were evaluated by use of the tissue-micro-array technique
      employing the following markers: CD3, CD4, CD8, CD20, CD68, FOXP3, Granzyme B. In
      the low-risk group high CD20+ infiltration was associated with a significantly
      better NED-survival rate (p=0.02). Contrary, among high-risk patients low CD20+
      counts indicated significantly better survival (p=0.03). Additionally, in the low
      risk group higher numbers of intraepithelial CD8+ TIL (>66.6 per thousand) led to
      improved NED-survival of 95% vs. 52% (p=0.005). The impact of TIL on prognosis in
      patients with head and neck cancer may be affected by type of treatment and stage
      of disease. This finding will influence future studies on the role of TIL in
      human cancers.

PMID- 19576840
TI  - Chasing the structures of small molecules in arbuscular mycorrhizal signaling.
AB  - The arbuscular mycorrhiza (AM) is a symbiosis between most terrestrial plants and
      fungi of the ancient phylum Glomeromycota. AM improves the uptake of water and
      mineral nutrients, such as phosphorus (P) and nitrogen (N), of the host plant in
      exchange for photosynthetically fixed carbon. Successful colonization and a
      functional interaction between host plant and mycobiont are based upon exchange
      of signaling molecules at different stages of symbiosis development.
      Strigolactones, a novel class of plant hormones, are secreted by plant roots
      stimulating presymbiotic growth of AM fungi. Fungi release soluble signaling
      molecules, the enigmatic 'Myc factors', that activate early symbiotic root
      responses. Lysophosphatidylcholine is a lipophilic intraradical mycorrhizal
      signal triggering plant phosphate transporter gene expression late in AM
      development through a P-controlled transcriptional mechanism. This enables uptake
      of orthophosphate released from the AM fungus.

PMID- 19576839
TI  - Differential induction of CYP1A1 and CYP1B1 by benzo[a]pyrene in oral squamous
      cell carcinoma cell lines and by tobacco smoking in oral mucosa.
AB  - Polyaromatic hydrocarbons, including benzo[a]pyrene (BP), are major tobacco
      carcinogens. Their carcinogenic effects require metabolic activation by
      cytochrome p450 (CYP) enzymes. Relative CYP isoform expression is related to
      tissue-specific tobacco-related squamous cell carcinoma (SCC) susceptibility.
      There have been conflicting reports regarding relative CYP1A1 and CYP1B1 oral
      expression, and information regarding CYP1B1 expression in oral tissues is
      limited. To quantify BP- and tobacco-induced CYP1A1 and CYP1B1 expression in oral
      SCC cells and oral mucosa. STUDY DESIGN: Real-time qPCR was performed to measure
      (1) BP-induced CYP1A1 and CYP1B1 mRNA expression in seven oral/other head and
      neck SCC cell lines (2) CYP1A1 and CYP1B1 mRNA expression in gingiva from 22
      smokers and 24 nonsmokers. SCC lines exhibited either similar induction of both
      isoforms or preferential CYP1A1 induction (CYP1A1-to-CYP1B1 ratios 0.8-4.3). In
      contrast, gingival tissues from smokers exhibited preferential CYP1B1 induction.
      Marked interindividual variation in CYP1A1 and CYP1B1 expression was observed
      among smokers. In vitro conditions may not account for factors that modulate
      expression in vivo. Interindividual variation in inducible CYP1A1 and CYP1B1
      expression may account in part for variation in tobacco-related oral SCC risk.

PMID- 19576841
TI  - Virus-host interactions: from systems biology to translational research.
AB  - Research embracing systems biology approaches and careful analysis of the
      critical host response has greatly expanded our understanding of infectious
      diseases. First-generation studies based on genomics and proteomics have made
      significant progress in establishing the foundation for network-based
      investigations on virus-host interactions. More recently, data from complementary
      high-throughput technologies, such as siRNA and microRNA screens and next
      generation sequencing, are augmenting systems level analyses and are providing a
      more detailed and insightful multidimensional view of virus-host networks.
      Together with advances in data integration, systems biology approaches now have
      the potential to provide profound impacts on translational research, leading to
      the more rapid development of new therapeutics and vaccines for infectious
      diseases. In this review, we highlight new high-throughput technologies, a new
      philosophy for studying virus-host interactions, and discuss the potential of
      systems biology to facilitate bench-to-bedside research and create novel
      strategies to combat disease. Can we save the world using these approaches? Read
      on.

PMID- 19576842
TI  - What have RNAi screens taught us about viral-host interactions?
AB  - The blossoming of genomic technologies and miniaturization has opened up the
      field of genomic scale cell-based screening to the study of viral-host
      interactions. RNAi technology, while still at its infancy, is being used to
      identify cellular factors required for various viral infections. This has led to
      the discovery of hundreds of new factors, and has increased our knowledge of the
      host factors that impact viral infection and highlighted the cellular pathways at
      play.

PMID- 19576843
TI  - Prediction of wood property in Chinese Fir based on visible/near-infrared
      spectroscopy and least square-support vector machine.
AB  - A method for the quantification of density of Chinese Fir samples based on
      visible/near-infrared (vis-NIR) spectrometry and least squares-support vector
      machine (LS-SVM) was proposed. Sample set partitioning based on joint x-y
      distances (SPXY) algorithm was used for dividing calibration and prediction
      samples, it is of value for prediction of property involving complex matrices. A
      stepwise procedure is employed to select samples according to their differences
      in both x (instrumental responses) and y (predicted parameter) spaces. For
      comparison, the models were also constructed by Kennard-Stone method, as well as
      by using the duplex and random sampling methods for subset partitioning. The
      results revealed that the SPXY algorithm may be an advantageous alternative to
      the other three strategies. To validate the reliability of LS-SVM, comparisons
      were made among other modeling methods such as support vector machine (SVM) and
      partial least squares (PLS) regression. Satisfactory models were built using LS
      SVM, with lower prediction errors and superior performance in relation to SVM and
      PLS. These results showed possibility of building robust models to quantify the
      density of Chinese Fir using near-infrared spectroscopy and LS-SVM combined SPXY
      algorithm as a nonlinear multivariate calibration procedure.

PMID- 19576844
TI  - Identification of the novel KI and WU polyomaviruses in human tonsils.
AB  - BACKGROUND: Three novel polyomaviruses have been recently discovered: KI, WU and
      MC polyomaviruses. Their role in human pathology is debated while tissue tropism
      and site of latency remain unknown. OBJECTIVE: To test the hypothesis that KI, WU
      and MC polyomaviruses can infect human tonsils. STUDY DESIGN: Archival paraffin
      embedded tonsils from 91 patients affected by different tonsil diseases were
      screened by polymerase chain reaction to detect viral DNA of KIV, WUV, MCV, BKV
      and JCV. Phylogenetic and evolutionary analysis of the identified polyomaviruses
      was carried out. RESULTS: Of the 91 tested specimens, 11 contained KIV DNA (12%),
      4 WUV DNA (4.4%), 5 BKV DNA (5.5%). MCV and JCV were not detected. Phylogenetic
      analysis showed that KIVs identified in tonsils fall into a clade distinct from
      that containing KIVs isolated from respiratory secretions, respiratory tissue and
      feces. Moreover, four positively selected sites (4.5% of t-Ag sites) were found
      under strong positive selection (omega=11.4), with posterior probabilities above
      0.99. All the sites were located in the N-terminal region of the small t antigen.
      CONCLUSIONS: The results suggest that the novel KI and WU polyomaviruses can
      infect human tonsils. Future studies are needed to define their role in tonsil
      diseases.

PMID- 19576845
TI  - Evaluation of the new VERSANT HIV-1 RNA 1.0 Assay (kPCR) for quantitative
      detection of human immunodeficiency virus type 1 RNA.
AB  - BACKGROUND: The VERSANT HIV-1 RNA 1.0 Assay (kPCR) for quantitative detection of
      HIV-1 RNA has recently been introduced. OBJECTIVES: In this study, the
      performance of the VERSANT HIV-1 RNA 1.0 Assay (kPCR) was evaluated and compared
      to the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, version 2.0. STUDY DESIGN:
      Accuracy, linearity, interassay and intra-assay variations were determined, and a
      total of 196 routine clinical samples including a high number of HIV-1 subtype
      non-B samples were investigated. RESULTS: When accuracy of the new kit was
      tested, all of the quantifiable results were found to be within -0.5log(10) unit
      of the expected panel results. Determination of linearity resulted in a
      quasilinear curve up to the initial concentration of 3.4x10(5)copies/mL. The
      interassay variation ranged from 12 to 20%, and the intra-assay variation ranged
      from 8 to 16%. When clinical samples were tested by the VERSANT HIV-1 RNA 1.0
      Assay (kPCR) and the results were compared with those obtained by the COBAS
      AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, the results for 95% of all
      samples with positive results by both tests were found to be within +/-1.0log(10)
      unit. The viral loads for all samples measured by the Siemens and Roche assays
      showed a high correlation (R(2)=0.94); quantitative results obtained by the
      Siemens assay were usually found to be lower than those obtained by the Roche
      assay. CONCLUSIONS: The new VERSANT HIV-1 RNA 1.0 Assay (kPCR) proved to be
      suitable for use in the routine diagnostic laboratory. The time to results was
      similar for both of the assays.

PMID- 19576846
TI  - The first detection of human parechovirus infections in China.

PMID- 19576847
TI  - Cognitive inhibition of number/length interference in a Piaget-like task:
      evidence by combining ERP and MEG.
AB  - OBJECTIVE: We combined event-related potential (ERP) and magnetoencephalography
      (MEG) acquisition and analysis to investigate the electrophysiological markers of
      the inhibitory processes involved in the number/length interference in a Piaget
      like numerical task. METHODS: Eleven healthy subjects performed four gradually
      interfering conditions with the heuristic "length equals number" to be inhibited.
      Low resolution tomography reconstruction was performed on the combined grand
      averaged electromagnetic data at the early (N1, P1) and late (P2, N2, P3(early)
      and P3(late)) latencies. Every condition was analyzed at both scalp and regional
      brain levels. RESULTS: The inhibitory processes were visible on the late
      components of the electromagnetic brain activity. A right P2-related frontal
      orbital activation reflected the change of strategy in the inhibitory processes.
      N2-related SMA/cingulate activation revealed the first occurrence of the stimuli
      processing to be inhibited. Both P3 components revealed the working memory
      processes operating in a medial temporal complex and the mental imagery processes
      subtended by the precuneus. CONCLUSIONS: Simultaneous ERP and MEG signal
      acquisition and analysis allowed to describe the spatiotemporal patterns of
      neural networks involved in the inhibition of the "length equals number"
      interference. SIGNIFICANCE: Combining ERP and MEG ensured a sensitivity which
      could be reached previously only through invasive intracortical recordings.

PMID- 19576848
TI  - Improving the identification of High Frequency Oscillations.
AB  - OBJECTIVE: High Frequency Oscillations (HFOs), including Ripples (80-250Hz) and
      Fast Ripples (250-500Hz), can be recorded from intracranial macroelectrodes in
      patients with intractable epilepsy. We implemented a procedure to establish the
      duration for which a stable measurement of rate of HFOs is achieved. METHODS: To
      determine concordance, Kappa coefficient was computed. The information gained
      when increasing the duration was analyzed in terms of HFO rates and ranking of
      channels with respect to HFO and spike rates. RESULTS: In a group of 30 patients,
      Kappa was 0.7 for ripples, 0.7 for fast ripples and 0.67 for spikes. Five minutes
      provided the same information as 10min in terms of rates in 9/10 patients and
      with respect to ranking of channels in 8/10 patients; 5/30 patients did not
      achieve stable measurements of HFOs or spikes and needed marking for 10min.
      CONCLUSION: We propose that 5min provides in most cases the same information as a
      longer interval when identifying HFOs and spikes in slow wave sleep, and present
      methods to identify when this is not the case. SIGNIFICANCE: This procedure is
      useful to control for consistency between readers and to evaluate if the selected
      interval provides stable information, for automatic and visual identification of
      events.

PMID- 19576849
TI  - Seizure prediction: any better than chance?
AB  - OBJECTIVE: To test whether epileptic seizure prediction algorithms have true
      predictive power, their performance must be compared with the one expected under
      well-defined null hypotheses. For this purpose, analytical performance estimates
      and seizure predictor surrogates were introduced. We here extend the Monte Carlo
      framework of seizure predictor surrogates by introducing alarm times surrogates.
      METHODS: We construct artificial seizure time sequences and artificial seizure
      predictors to be consistent or inconsistent with various null hypotheses to
      determine the frequency of null hypothesis rejections obtained from analytical
      performance estimates and alarm times surrogates under controlled conditions.
      RESULTS: Compared to analytical performance estimates, alarm times surrogates are
      more flexible with regard to the testable null hypotheses. Both approaches have
      similar, high statistical power to indicate true predictive power. For Poisson
      predictors that fulfill the null hypothesis of analytical performance estimates,
      the frequency of false positive null hypothesis rejections can exceed the
      significance level for long mean inter-alarm intervals, revealing an intrinsic
      bias of these analytical estimates. CONCLUSIONS: Alarm times surrogates offer
      important advantages over analytical performance estimates. SIGNIFICANCE: The key
      question in the field of seizure prediction is whether seizures can in principle
      be predicted or whether algorithms which have been presumed to perform better
      than chance actually are unable to predict seizures and simply have not yet been
      tested against the appropriate null hypotheses. Alarm times surrogates can help
      to answer this question.

PMID- 19576850
TI  - Analysis of a reactive agility field test.
AB  - The purpose of this research was to evaluate a reactive agility test by
      determining the relationships between the total time recorded for the test and
      various components. A tester used side-step movements to provide a stimulus for
      the athlete to change direction. By using electronic timing and high speed video
      analysis of the test, three times were recorded. These were the time taken for
      the tester to display the stimulus to change direction (tester time), the time
      taken by the participant to respond to the stimulus (decision time), and the time
      taken by the participant to change direction and sprint to the left or right
      (response movement time). Thirty-one semi-professional Australian Rules football
      players were assessed by analysing the mean of eight trials of the reactive
      agility test. The greatest correlation with total time was r=0.77 for decision
      time (p=0.00), with movement time and tester time producing coefficients of 0.59
      (p=0.00) and 0.37 (p=0.04), respectively. The coefficient of variation for the
      mean tester time was 5.1%. It was concluded that perceptual skill as measured by
      decision time is an important component of the reactive agility test and the
      tester time should be controlled by using high speed video recordings to isolate
      its influence.

PMID- 19576851
TI  - An immunohistochemical procedure to detect patients with paraganglioma and
      phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a
      retrospective and prospective analysis.
AB  - BACKGROUND: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours
      that occur sporadically and in several hereditary tumour syndromes, including the
      phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline
      mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes.
      Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised,
      although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas
      harbour germline SDH-gene mutations. Despite these figures, the screening of
      phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect
      phaeochromocytoma-paraganglioma syndrome is rarely done because of time and
      financial constraints. We investigated whether SDHB immunohistochemistry could
      effectively discriminate between SDH-related and non-SDH-related
      phaeochromocytomas and paragangliomas in large retrospective and prospective
      tumour series. METHODS: Immunohistochemistry for SDHB was done on 220 tumours.
      Two retrospective series of 175 phaeochromocytomas and paragangliomas with known
      germline mutation status for phaeochromocytoma-susceptibility or paraganglioma
      susceptibility genes were investigated. Additionally, a prospective series of 45
      phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining
      followed by SDHB, SDHC, and SDHD mutation testing. FINDINGS: SDHB protein
      expression was absent in all 102 phaeochromocytomas and paragangliomas with an
      SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours
      related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and
      neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and
      paragangliomas with no syndromic germline mutation showed SDHB expression. The
      sensitivity and specificity of the SDHB immunohistochemistry to detect the
      presence of an SDH mutation in the prospective series were 100% (95% CI 87-100)
      and 84% (60-97), respectively. INTERPRETATION: Phaeochromocytoma-paraganglioma
      syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB,
      SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB
      negative tumours. SDHB immunohistochemistry on phaeochromocytomas and
      paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma
      syndrome. FUNDING: The Netherlands Organisation for Scientific Research, Dutch
      Cancer Society, Vanderes Foundation, Association pour la Recherche contre le
      Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC
      grant COMETE 3 for the COMETE network.

PMID- 19576852
TI  - Hit finding: towards 'smarter' approaches.
AB  - Drug discovery is complex and risky, and the chances of success are low. One
      starting point to discover a new drug is the selective screening of a collection
      of high value and good quality compounds. Selection of compounds for screening is
      one of the challenging initial steps in the drug discovery process and is crucial
      for the success of the project. Optimal selection will enhance the chances of
      successful hit finding with regard to both number and quality of hits. Several
      scenarios for compound selection can be envisaged, and are primarily driven by
      knowledge of the target. Deciding the most appropriate scenario is important and
      appropriate software packages and chemoinformatics tools are available for these
      purposes. After screening, researchers may face challenges in selecting the best
      hits for further optimization. Numerous chemoinformatics tools have emerged
      recently to address challenges in hit analysis, prioritization and optimization.

PMID- 19576853
TI  - BP-DBS for dystonia-choreoathetosis cerebral palsy.

PMID- 19576855
TI  - Commentary to "Controversies in the management of vesicoureteral reflux - the
      rationale for the RIVUR study".

PMID- 19576854
TI  - Bilateral pallidal deep brain stimulation for the treatment of patients with
      dystonia-choreoathetosis cerebral palsy: a prospective pilot study.
AB  - BACKGROUND: Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause
      of disability in children and in adults, and responds poorly to medical
      treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus
      pallidus internus (GPi) is an effective treatment for primary dystonia, but the
      effect of this reversible surgical procedure on dystonia-choreoathetosis CP,
      which is a subtype of secondary dystonia, is unknown. Our aim was to test the
      effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP. METHODS: We
      did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia
      choreoathetosis CP who had no cognitive impairment, little spasticity, and only
      slight abnormalities of the basal ganglia on MRI. The primary endpoint was change
      in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as
      assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of
      surgical targeting to the GPi was assessed masked to the results of
      neurostimulation. Analysis was by intention to treat. FINDINGS: The mean Burke
      Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1)
      before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean
      improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and
      mental health-related quality of life were significantly improved. There was no
      worsening of cognition or mood. Adverse events were related to stimulation
      (arrest of the stimulator in one patient, and an adjustment to the current
      intensity in four patients). The optimum therapeutic target was the
      posterolateroventral region of the GPi. Little improvement was seen when the
      neurostimulation diffused to adjacent structures (mainly to the globus pallidus
      externus [GPe]). INTERPRETATION: Bilateral pallidal neurostimulation could be an
      effective treatment option for patients with dystonia-choreoathetosis CP.
      However, given the heterogeneity of motor outcomes and the small sample size,
      results should be interpreted with caution. The optimum placement of the leads
      seemed to be a crucial, but not exclusive, factor that could affect a good
      outcome. FUNDING: National PHRC; Cerebral Palsy Foundation: Fondation
      Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

PMID- 19576857
TI  - Increased lymphocyte viability after non-stimulated peripheral blood mononuclear
      cell (PBMC) culture in patients with X-linked lymphoproliferative disease (XLP).
AB  - Survival of lymphocytes after prolonged culture was studied in two asymptomatic
      XLP patients. Viability of XLP PBMC after 30 days of non-stimulated culture was
      higher than that of normal controls (N), mainly due to the persistence of CD8
      memory lymphocytes. IFNgamma high CD8 T lymphocytes remained higher in XLP than
      in N after 30 days. The number of perforin+ CD8 lymphocytes was markedly reduced
      after 30 days in XLP and in N. Increased viability was not related to CD127, PD
      1, CD27, or CD62L expression. Concerning B lymphocytes, memory CD27+ CD19+ cells
      prevailed over CD27- cells after 30 days in both XLP and N, with far more
      surviving cells in XLP. In N, few CD19+ B lymphocytes were viable after prolonged
      culture. In XLP, these cells were also IgD+, IgM+ and EBNA2+. These results
      demonstrate that IFNgamma-positive memory CD8 T cells persist in XLP after
      prolonged culture in association with a subset of viable memory CD27+ B cells
      expressing latent EBV antigens. The survival advantage of XLP cells might be
      related to increased frequency of extranodal lymphoma in XLP patients.

PMID- 19576856
TI  - Comprehensive seroprofiling of sixteen B. burgdorferi OspC: implications for Lyme
      disease diagnostics design.
AB  - Early diagnosis of Lyme disease (LD) is critical to successful treatment.
      However, current serodiagnostic tests do not reliably detect antibodies during
      early infection. OspC induces a potent early immune response and is also one of
      the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the
      amino acid sequence is conserved among all 21 known OspC types. We performed a
      series of comprehensive seroprofiling studies to select the OspC types that have
      the most cross-reactive immunodominant epitopes. We found that proteins belonging
      to seven OspC types detect antibodies from all three infected host species
      regardless of the OspC genotype of the infecting strain. Although no one OspC
      type identifies all seropositive human samples, combinations of as few as two
      OspC proteins identified all patients that had anti-OspC antibodies.

PMID- 19576858
TI  - Abnormal uterine and post-menopausal bleeding in the acute gynaecology unit.
AB  - Abnormal uterine bleeding is one of the most common presentations in the acute
      gynaecology unit. The general principles of emergency care, including assessment
      of haemodynamic state, symptomatic relief as well as determination of underlying
      aetiology, apply to these women. We review different strategies in the diagnosis
      and investigation of abnormal uterine bleeding in both pre- and post-menopausal
      women. Transvaginal ultrasound (TVS) with colour Doppler is the cornerstone of
      initial management. TVS, in experienced hands, can reliably exclude the most
      common intra-cavitary pathologies including endometrial polyps and submucosal
      fibroids. Their exclusion, in pre-menopausal women, aids in the diagnosis of
      dysfunctional uterine bleeding. In post-menopausal women, the endometrial
      thickness reliably selects those who need further testing. If a thin and regular
      endometrium is visualised, malignancy is most unlikely. To allow for reliable
      evaluation of the endometrium, TVS has to be performed before endometrial
      sampling. Saline infusion sonohysterography (SIS) is most valuable in the
      detection of focal intra-cavitary lesions. TVS with or without SIS can provide
      enough information to avoid an unnecessary hysteroscopy. In this review, we will
      also discuss an evidence-based algorithm for the work-up of women with post
      menopausal bleeding.

PMID- 19576859
TI  - Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is
      maintained by sympathoadrenal catecholamines.
AB  - Although stress plays an important role in chronic widespread pain syndromes,
      such as fibromyalgia, the underlying mechanism has remained elusive. We have
      recently demonstrated, in a model of chronic widespread pain, that prolonged
      enhancement of immune mediator hyperalgesia, induced by unpredictable sound
      stress, requires a contribution of both the sympathoadrenal (epinephrine) and the
      hypothalamic-pituitary adrenal (corticosterone) neuroendocrine stress axes.
      Because this stress protocol produced sustained elevation of plasma epinephrine,
      in the current study we tested the hypothesis that the sympathoadrenal axis also
      plays a role in maintenance of symptoms in this model of chronic widespread pain.
      After establishment, adrenal medullectomy abolished the enhancement of
      epinephrine-induced cutaneous and muscle hyperalgesia. Administration of stress
      levels of epinephrine to adrenal medullectomized rats reconstituted the pain
      phenotype. These observations suggest that the sympathoadrenal stress axis plays
      a major role in the induction as well as maintenance of stress-induced
      enhancement of mechanical hyperalgesia, mediated by prolonged elevation of
      circulating epinephrine. PERSPECTIVE: We present data showing mechanical
      hyperalgesia persisting for up to 28 days after exposure to sound stress, with
      evidence that the sympathoadrenal axis mediator epinephrine plays a major role.
      These findings could have clinical implications with regard to novel potential
      treatments for chronic widespread pain syndromes, such as fibromyalgia.

PMID- 19576860
TI  - Pharmacokinetics of pefloxacin mesylate in human urine using capillary
      electrophoresis electrochemiluminescence detection.
AB  - A novel and simple method to determine pharmacokinetics of pefloxacin mesylate
      (PM) in urine of seven healthy adults was developed. The proposed methodology was
      based on the electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium
      (II) at a platinum electrode. The ECL intensity was found greatly enhanced in the
      presence of PM, which could directly participate in the light-emitting reaction
      as the reductant (in former/unchanged form). Under optimised conditions, the
      calibration curve was linear from 0.02 to 12 mg/L with a detection limit of 0.004
      mg/L (sigma=3). The RSD of the peak height was less than 2.4% (n=6). The
      recoveries in human urine were 96.2% to 98.3%. The highest excretion rate in
      urine was observed during the period 1.5-2 h after oral administration. The
      urinary excretion ratio of PM was 13.6% within 48 h.

PMID- 19576861
TI  - Method validation, comparison and transfer.

PMID- 19576862
TI  - Optical coherence tomography in children with coeliac disease.

PMID- 19576863
TI  - Pulmonary embolism following thrombosis of the brachial vein after shoulder
      arthroscopy. A case report.
AB  - Thromboembolic complications are very rare after arthroscopic surgery of the
      shoulder. We report the case of a 25-year-old who presented thrombophlebitis of
      the brachial vein complicated by pulmonary embolism following arthroscopic
      surgery for posterior instability of the shoulder. No hemostasis impairment was
      found in this patient. The factors arguing in favor of thrombosis that had been
      retained from the literature were the lateral decubitus position with traction of
      the limb in its axis, prolonged surgical time, use of interscalene brachial
      plexus block, and a general condition susceptible to thrombosis (personal or
      family history of thromboembolism, genetic risk factor for thrombosis, smoking,
      obesity, neoplasia). There are currently no guidelines on the need for
      thromboembolism prevention during shoulder arthroscopy.

PMID- 19576864
TI  - Functionalized silicon quantum dots tailored for targeted siRNA delivery.
AB  - For RNA interference (RNAi) mediated silencing of the ABCB1 gene in Caco-2 cells
      biocompatible luminescent silicon quantum dots (SiQDs) were developed to serve as
      self-tracking transfection tool for ABCB1 siRNA. While the 2-3nm sized SiQD core
      exhibits green luminescence, the QD surfaces are completely saturated with
      covalently linked 2-vinylpyridine that may electrostatically bind siRNA. For down
      regulating P-glycoprotein (Pgp) expression of the ABCB1 gene the SiQDs were
      complexed with siRNA. The cellular uptake and allocation of SiQD-siRNA complexes
      in Caco-2 cells were monitored using confocal laser scanning microscopy and
      transmission electron microscopy. The release of siRNA to the cytoplasm was
      verified through real-time PCR quantification of the reduced ABCB1 mRNA level.
      Additional evidence was obtained from time-resolved in situ fluorescence
      spectroscopic monitoring of the Pgp efflux dynamics in transfected Caco-2 cells
      which yielded significantly reduced transporter efficiencies for the Pgp
      substrate Rhodamine 123.

PMID- 19576866
TI  - Inhibitory mechanisms of heterocyclic carboxaldehyde thiosemicabazones for two
      forms of human ribonucleotide reductase.
AB  - Two forms of ribonucleotide reductase (RR), consisting of M1 with M2 subunits and
      M1 with p53R2 subunits, are involved in DNA replication and damage repair,
      respectively. 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3AP), one of
      the heterocyclic carboxaldehyde thiosemicabazones (HCTs), is a potent RR
      inhibitor in clinical trial for cancer treatment. In this study, 3AP and its 7
      derivatives showed 100-1000-fold higher inhibitory potency on KB nasopharyngeal
      carcinoma cells than hydroxyurea and were fully active against hydroxyurea- and
      gemcitabine-resistant KB cells. In vitro RR assays using two recombinant RRs
      showed that all 8 HCTs decreased the activity of both RRs in a dose-dependent
      manner and the efficiency was compatible with that on cell proliferation
      inhibition. Iron has different impact on the behavior of the compounds toward
      RRs. In the absence of iron, the HCTs showed more selective inhibition for p53R2
      M1 than M2-M1, while addition of iron increased their activity but reduced their
      selectivity for two RRs. Radioligand binding assays showed that [(3)H]3AP
      directly bounded to the small subunits. Electron paramagnetic resonance
      measurements demonstrated that these HCTs generated reactive oxygen species with
      ferrous iron, which quenched the diiron-tyrosyl radical co-factor of the small
      subunits and hence the enzyme activity. While the ROS may be a common mediator
      responsible for the potent activity of the HCTs, the different characteristics of
      the small subunit proteins are probably associated with the subunit-selectivity
      of inhibition. Better understanding of the mechanism of action of RR inhibition
      may improve design of new potent and subunit-selective RR inhibitors for cancer
      therapy.

PMID- 19576865
TI  - Nitro-aspirin inhibits MCF-7 breast cancer cell growth: effects on COX-2
      expression and Wnt/beta-catenin/TCF-4 signaling.
AB  - There is current evidence implicating the Wnt/beta-catenin/TCF pathway in breast
      cancer. We investigated the effect of para- and meta-positional isomers of nitric
      oxide-releasing aspirin (NO-ASA), and aspirin (ASA) on MCF-7 human breast cancer
      cell growth and beta-catenin/TCF signaling. The p- and m-NO-ASA isomers strongly
      inhibited cell growth and beta-catenin/TCF transcriptional activity compared to
      ASA; the IC50s for growth inhibition were 57+/-4, 193+/-10 and >5000microM, and
      for transcriptional inhibition they were 12+/-1.8, 75+/-6.5 and >5000microM for p
      , m-NO-ASA and ASA, respectively. p-NO-ASA reduced the expression of Wnt/beta
      catenin downstream target gene cyclin D1, and total cellular beta-catenin levels.
      COX-2 expression was induced by p-NO-ASA, protein kinase C inhibitors reversed
      this induction. p-NO-ASA blocked the cell cycle transition at S to G2/M phase.
      These studies suggest a targeted chemopreventive/chemotherapeutic potential for
      NO-ASA against breast cancer.

PMID- 19576867
TI  - Enhanced nicotine reward in adulthood after exposure to nicotine during early
      adolescence in mice.
AB  - Approximately one million adolescents begin smoking cigarettes every year.
      Studies show that adolescents may be particularly vulnerable to various aspects
      of nicotine dependence. Work on rodents demonstrates parallel findings showing
      that adolescence is a time of changed sensitivity to both rewarding and aversive
      effects of nicotine. However, it is unclear if these effects are long-lasting and
      whether they contribute to a lifetime of nicotine addiction. In this study we
      have characterized the effects of adolescent nicotine exposure on the rewarding
      properties of nicotine in adulthood using the CPP model. Specifically, we have
      addressed whether the phase of adolescence (early, middle, or late adolescence)
      plays a role in the susceptibility to the enhanced rewarding effects of nicotine.
      Furthermore, we have investigated the long-term effects of adolescent nicotine
      exposure on nicotine reward in adulthood and have correlated these behavioral
      adaptations with possible molecular mechanisms. We observed that early
      adolescence in the mouse is a unique phase for elevated sensitivity to nicotine
      reward using a CPP model. In addition, exposure to nicotine during this phase,
      but not during late adolescence or adulthood, resulted in a lasting enhancement
      of reward in adulthood. Finally, we have shown that early adolescent nicotine
      exposure significantly elevates nAChR function in adulthood. Overall, we
      demonstrate that early adolescence represents a period of development, distinct
      from middle and late adolescence, during which nicotine exposure can cause
      persistent changes in behavior and molecular adaptations.

PMID- 19576870
TI  - Fatty acids increase paracellular absorption of aluminium across Caco-2 cell
      monolayers.
AB  - Passive paracellular absorption, regulated by tight junctions (TJs), is the main
      route for absorption of poorly absorbed hydrophilic substances. Surface active
      substances, such as fatty acids, may enhance absorption of these substances by
      affecting the integrity of TJ and increasing the permeability. It has been
      suggested that aluminium (Al) absorption occurs mainly by the paracellular route.
      Herein, we investigated if physiologically relevant exposures of fully
      differentiated Caco-2 cell monolayers to oleic acid and docosahexaenoic acid
      (DHA), which are fatty acids common in food, increase absorption of Al and the
      paracellular marker mannitol. In an Al toxicity test, mannitol and Al absorption
      through Caco-2 cell monolayers were similarly modulated by Al concentrations
      between 1 and 30mM, suggesting that absorption of the two compounds occurred via
      the same pathways. Exposure of Caco-2 cell monolayers to non-toxic concentrations
      of Al (2mM) and (14)C-mannitol in fatty acid emulsions (15 and 30mM oleic acid, 5
      and 10mM DHA) caused a decreased transepithelial electrical resistance (TEER).
      Concomitantly, fractional absorption of Al and mannitol, expressed as percentage
      of apical Al and mannitol retrieved at the basolateral side, increased with
      increasing dose of fatty acids. Transmission electron microscopy was applied to
      assess the effect of oleic acid on the morphology of TJ. It was shown that oleic
      acid caused a less structured morphology of TJ in Caco-2 cell monolayers. Taken
      together our findings indicate that fatty acids common in food increase the
      paracellular intestinal absorption of Al. These findings may influence future
      risk assessment of human Al exposure.

PMID- 19576869
TI  - A positive change in energy balance modulates TrkB expression in the hypothalamus
      and nodose ganglia of rats.
AB  - Brain-derived neurotrophic factor (BDNF) and its TrkB receptor play critical
      roles in the synaptic activity and plasticity of mature neurons and enhance adult
      neurogenesis. Furthermore, treatment with BDNF has been found to attenuate weight
      gain or even cause weight loss and appetite suppression in rats. The aim of this
      study was to look at the effect of nutrient intake on BDNF concentrations and
      cellular proliferation in the brain. Adult male Wistar rats were given one of
      three diets for 6 weeks: high-carbohydrate, high-fat or high-fat pair-fed diets.
      Rats were sacrificed at the end of the feeding period and BDNF concentrations in
      the dorsal vagal complex (DVC), hypothalamus and plasma were measured by ELISA on
      protein extracts of these samples. Cellular proliferation in the DVC was
      quantified by Ki-67 immunohistochemistry. Neither BDNF levels nor proliferation
      were modified by the diet. Secondly, using rats that received the same diets,
      real-time PCR was performed in the DVC, hypothalamus and nodose ganglia in order
      to compare TrkB receptor levels. The results showed significantly lower TrkB
      levels in the hypothalamus and nodose ganglia of fasted rats receiving the high
      fat diet when compared to the other groups. These two complementary
      methodological approaches suggest that there is a relationship between long-term
      dietary intake and BDNF. More precisely, TrkB expression is more responsive to
      energy states than to diet composition. An increment in energy stores thus
      triggers decreased BDNF anorexigenic signaling at the receptor level in the
      hypothalamus and nodose ganglia, but not in the DVC.

PMID- 19576868
TI  - Individual differences in risk preference predict neural responses during
      financial decision-making.
AB  - We investigated the neural correlates of subjective valuations during a task
      involving risky choices about lotteries. Because expected value was held constant
      across all lotteries, decisions were influenced by subjective preferences, which
      manifest behaviorally as risk-seeking or risk-averse attitudes. To isolate
      structures encoding risk preference during choice, we probed for areas showing
      increased activation as a function of selected risk-level. Such response patterns
      were obtained in anterior (ACC) and posterior cingulate cortex (PCC), superior
      frontal gyrus, caudate nucleus, and substantia nigra. Behavioral results revealed
      the presence of risk-averse and risk-neutral individuals. In parallel, brain
      signals revealed modulation of activity by risk attitude during choice.
      Correlations between risk-seeking attitudes and neural activity during risky
      choice were obtained in superior and inferior frontal gyri, medial and lateral
      orbitofrontal cortex, and parahippocampal gyrus, while correlations with risk
      averse attitudes were found in the caudate. The dynamics of neural responses
      relevant to each stage of the task (decision, anticipation, outcome) were
      investigated via timeseries and conjunction analyses. Though the networks engaged
      in each of the task stages were mostly distinct, regions within ACC, PCC and
      caudate were consistently activated during each decision-making phase. These
      results demonstrate (1) that subjective assessments of risk, as well as
      individual attitudes toward risk, play a significant role in modulating activity
      within brain regions recruited during decision-making, and (2) that ACC, PCC and
      caudate are relevant during each phase of a decision-making task requiring
      subjective valuations, strengthening the role of these regions in self
      referential subjective valuations during choice.

PMID- 19576871
TI  - Bioactivation of coumarin in rat olfactory mucosal microsomes: Detection of
      protein covalent binding and identification of reactive intermediates through
      analysis of glutathione adducts.
AB  - The presence of high levels, as well as tissue-specific forms, of cytochrome P450
      enzymes in mammalian olfactory mucosa (OM) has important implications in the
      bioactivation and toxicity of xenobiotics entering the tissue. Previous studies
      have shown that coumarin, a known olfactory toxicant in rats, is bioactivated by
      OM microsomal P450s to a number of products, presumably via coumarin-3,4-epoxide
      and other epoxide intermediates. The aim of the current study was to obtain
      direct evidence for the formation of such reactive intermediates in rat OM
      through the detection of protein covalent binding and glutathione (GSH) adduct
      formation. Protein covalent binding experiments with [(14)C]coumarin (10microM)
      displayed a 7-9-fold higher NADPH-dependent radioactivity binding in rat OM
      microsomes (2.5nmol/mg/30min) compared to those in rat and human liver
      microsomes; the binding value in rat OM microsomes was substantially but not
      completely reduced by the addition of GSH (5mM). LC/MS analyses detected a number
      of GSH adducts in GSH-supplemented coumarin metabolism reaction in rat OM
      microsomes; 3-glutathionyl coumarin was found to be the major one, indicating 3,4
      epoxidation as the main bioactivation pathway. Additional GSH adducts were
      identified, presumably forming via the same pathway or epoxidation on the benzene
      moiety. Our findings provide direct evidence for the formation of multiple
      coumarin reactive intermediates in rat OM, leading to protein covalent binding
      and GSH conjugation.

PMID- 19576872
TI  - Manipulations of metallothionein gene dose accelerate the response to Listeria
      monocytogenes.
AB  - Metallothioneins (MTs) are cysteine-rich proteins that assist in cellular
      homeostasis and protect against oxidant injury. MTs can be induced by heavy
      metals and inflammatory mediators and function as free radical scavengers,
      reservoirs for essential heavy metals, and immunomodulators. In light of MTs'
      roles in responses to stress, we evaluated the in vivo effects of MT gene dose on
      the course of Listeria monocytogenes (LM) infection. LM burden was measured in
      livers and spleens, and flow cytometric assays were used to analyze splenocyte
      surface sulfhydryls, oxidative burst and apoptosis. Our results suggest that
      deviations from the normal complement of MT genes alter the course of LM
      infection. Compared to the wild-type C57BL/6J (B6-WT) strain, a congenic partner
      that carries a larger number of Mt1 genes (B6-MTTGN) and a congenic strain in
      which both Mt1 and Mt2 are disrupted (B6-MTKO) both showed lower bacterial
      burdens three days post-inoculation. This difference was prominent in the first
      48h of infection, after which LM clearance occurred at comparable rates in all
      three strains. Lymphocytes from B6-MTKO mice exhibited increased cell death and
      increased levels of surface sulfhydryls compared to B6-WT and B6-MTTGN mice.
      Lymphocytes from B6-MTTGN mice had increased levels of intracellular oxidants
      compared to B6-WT and B6-MTKO mice. The oxidative burst by macrophages from
      infected B6-MTTGN and B6-MTKO mice was increased, suggesting one mechanism by
      which these strains might reduce the LM burden. These results indicate that MT
      gene dose dramatically influences host-defenses against LM infection.

PMID- 19576873
TI  - Autoantibodies to asialoglycoprotein receptor (ASGPR) measured by a novel ELISA-
      revival of a disease-activity marker in autoimmune hepatitis.
AB  - BACKGROUND: The liver-specific ASGPR is an autoantigen in autoimmune hepatitis
      (AIH) patients. Anti-ASGPR antibody correlates with disease activity, however,
      only in-house assays have been reported so far. METHODS: Rabbit ASGPR was
      purified by affinity chromatography on galactose-Sepharose and used for
      standardised detection of anti-ASGPR by ELISA. Anti-ASGPR IgG was measured in
      sera from 45 patients with AIH, PBC (n=43), alcoholic liver disease (n=13), HBV
      infection (n=35), HCV infection (n=53), and 118 blood donors. Anti-ASGPR was
      correlated with biochemical parameters of disease activity in 22 AIH patients
      with consecutive samples. RESULTS: Twenty-one of 30 untreated (70%) and five of
      15 treated AIH patients (30%) showed elevated anti-ASGPR at first presentation.
      Only one blood donor demonstrated anti-ASGPR. ALD and PBC patients were all
      negative. ROC curve analysis of AIH and disease-control patients revealed a
      sensitivity of 77.8% and a specificity of 99.4%. Three (8.6%) of 35 HBV and 7
      (13.2%) of 53 HCV patients demonstrated elevated anti-ASGPR. In AIH patients,
      anti-ASPGR correlated with liver-transaminases levels. In 22 follow-up patients,
      elevation of anti-ASPGR preceded liver-transaminases increase. CONCLUSIONS: The
      novel anti-ASGPR ELISA is a readily available and specific diagnostic tool for
      anti-ASGPR detection in AIH. Quantification of anti-ASGPR is helpful in
      monitoring disease activity.

PMID- 19576874
TI  - Serum levels of gamma-glutamyl transferase are associated with markers of
      nocturnal hypoxemia in a general adult population.
AB  - BACKGROUND: Serum gamma-glutamyl transferase (GGT) is a well-known marker of
      alcohol consumption and liver dysfunction. GGT is also associated with components
      of metabolic syndrome, cardiovascular risk factors and obstructive sleep apnea.
      In a population-based study, we investigated serum GGT levels in relation to
      markers of nocturnal hypoxemia, adjusting for potential confounders. In addition,
      we investigated the possible relationship between GGT concentrations and serum
      levels of tumour necrosis factor-alpha and interleukin-6. METHODS: Demographic
      data, alcohol consumption, components of metabolic syndrome, serum liver enzymes,
      pro-inflammatory cytokines and nocturnal pulse oximetry were available for 220
      individuals, randomly selected from a general adult population. Of these,
      overnight polysomnography was available for 70. RESULTS: A smoothing regression
      model confirmed that serum GGT levels were associated positively and
      independently with male sex (P<0.001), ageing (P=0.001), heavy smoking (P=0.039),
      alcohol drinking (P<0.001), and body mass index (P=0.019). Serum GGT levels were
      associated negatively and independently with average arterial oxygen saturation
      during sleep (P=0.001). CONCLUSIONS: Serum concentrations of GGT are associated
      with nocturnal arterial oxygen desaturations.

PMID- 19576875
TI  - Development of a rapid and sensitive magnetic chemiluminescent enzyme immunoassay
      for detection of luteinizing hormone in human serum.
AB  - OBJECTIVES: A rapid and sensitive magnetic particles (MPs)-based
      chemiluminescence enzyme immunoassay (MPs-CLEIA) for determination of luteinizing
      hormone (LH) in human serum was developed and validated. DESIGN AND METHODS: The
      method was developed based on a sandwiched immunoreaction format, in which MPs
      served as both the solid phase and separator. The horseradish peroxidase(HRP)
      luminol-H(2)O(2) chemiluminescent system was chosen as the detection system.
      RESULTS: This method had a detection limit of 0.2 mIU/mL and a linear range of
      0.5-200 mIU/mL. The assay showed little cross-reactivity, and the intra- and
      inter-assay coefficients of variation were less than 10%. The recoveries were
      from 101.6% to 104.1%. The method has been successfully applied to detection of
      LH in human serum and showed good correlation compared with radioimmunoassay
      (RIA). CONCLUSION: The MPs-CLEIA provided apparent advantages over RIA, and
      facilitated the development of high-throughput screening and automated operation
      systems in clinical diagnosis.

PMID- 19576876
TI  - Use of cyst fluid CEA, CA19-9, and amylase for evaluation of pancreatic lesions.
AB  - OBJECTIVES: The study goals were development of reference intervals and an
      interpretive algorithm for pancreatic cyst fluid tumor markers. DESIGN AND
      METHODS: 442 pancreatic cyst fluids were tested for CEA, CA19-9, and amylase.
      RESULTS: CEA>30 ng/mL discriminates mucinous from non-mucinous cysts. After CEA
      analysis, amylase and CA19-9 segregate non-mucinous and mucinous subtypes,
      respectively. CONCLUSIONS: Pancreatic cyst fluid tumor markers supplement other
      diagnostic measures. This study provides estimated reference intervals and an
      algorithm for interpretation.

PMID- 19576877
TI  - Prognostic value of serum vascular endothelial growth factor in Egyptian females
      with metastatic triple negative breast cancer.
AB  - OBJECTIVES: The aim of this work was to explore the value of serum vascular
      endothelial growth factor-A (VEGF-A) in patients with metastatic triple negative
      breast cancer (TNBC) treated with chemotherapy. The primary end point was overall
      survival (OS). Secondary end points were response rate (RR), progression-free
      survival (PFS) and VEGF-A level at baseline, mid-therapy and at the end of
      therapy. DESIGN AND METHODS: Female patients aged 18 years or above with
      histologically proven metastatic TNBC were included. Serum VEFG-A levels were
      measured at baseline, after the 3rd and 6th cycles of FAC chemotherapy regimen
      (Fluorourcil, Adriamycin, and Cyclophamide). RESULTS: The overall RR was 57%. The
      median PFS and OS were 7 and 11.2 months, respectively (95% CI: 4.3-9.7 and 3.8
      18.5 months, respectively). Patients whose disease progressed despite therapy had
      a significantly higher baseline VEGF-A level than those who did not progress.
      VEGF-A level did not drop with continuation of therapy. Patients with high VEGF-A
      level had a significantly lower PFS but not OS than patients with low levels.
      CONCLUSION: The outcome of metastatic TNBC is poor with FAC chemotherapy regimen.
      Alternative chemotherapeutic regimens and novel therapeutic approaches including
      targeting of VEGF and/or its receptors are warranted.

PMID- 19576878
TI  - Antagonistic interactions between Arabidopsis K-homology domain genes uncover
      PEPPER as a positive regulator of the central floral repressor FLOWERING LOCUS C.
AB  - Plant floral transition is a major developmental switch regulated by an
      integrated network of pathways. Arabidopsis FLOWERING LOCUS K (FLK), a protein
      with three KH RNA-binding domains, operates in the autonomous flowering-promotive
      pathway by decreasing the transcript levels of the key flowering repressor
      FLOWERING LOCUS C (FLC). Here we report that PEPPER (PEP), an FLK paralog
      previously shown to affect vegetative and pistil development, antagonizes FLK by
      positively regulating FLC. Lack of PEP function rescues the flk late-flowering
      phenotype with a concomitant decrease in FLC RNA levels. Loss of HUA2, another
      FLC activator encoding an RNA-binding protein, further rescues flk, being flk
      hua2 pep triple mutants virtually wild-type regarding flowering time.
      Consistently, PEP overexpression determines high levels of FLC transcripts and
      flowering delay. Genetic and molecular analyses indicate that FLK and PEP act
      independently of FCA, another important FLC repressor in the autonomous pathway.
      In addition, we present data suggesting that PEP may affect FLC expression at
      both transcriptional and post-transcriptional levels. Overall, our results
      uncover PEP as a new factor for FLC upregulation, underscoring the importance of
      RNA-binding activities during developmental timing of flowering.

PMID- 19576879
TI  - Estradiol increases catecholamine levels in the hypothalamus of ovariectomized
      rats during the dark-phase.
AB  - Estrogens modulate critical homeostatic functions of the hypothalamus such as
      temperature regulation, sexual behavior and sleep with the most pronounced
      effects in rats occurring during the dark-phase. The neurochemical signals
      underlying estrogenic regulation of these hypothalamic functions have not been
      clearly identified, possibly due to the fact that previous studies have not
      explored the effects of estrogen treatments on neuronal signaling during the dark
      phase. In the present study, ovariectomized rats received estradiol benzoate (5
      microg/rat for 7 days, s.c.) and norepinephrine and dopamine levels were measured
      in the preoptic area of the hypothalamus across the light/dark cycle using in
      vivo microdialysis. Estradiol benzoate treatment increased extracellular
      norepinephrine and dopamine levels relative to vehicle treatment during the dark
      phase. Increases in norepinephrine and dopamine were first detected by 30 min and
      5.5h after lights-off, respectively. Subsequent increases in norepinephrine and
      dopamine were also noted throughout the 9.5-h collection period. The effect of
      estradiol benzoate on catecholamine release did not correlate with increases in
      either tyrosine hydroxylase (TH) protein expression or activity levels in the
      anterior hypothalamus, although a marked decrease in TH activity correlated with
      a rise in extracellular norepinephrine at the beginning of the dark-phase. We
      conclude that subchronic estradiol benzoate treatment increases extracellular
      catecholamine levels in the preoptic area of the hypothalamus during the dark
      phase without a concomitant increase in neurotransmitter biosynthesis. The
      estradiol benzoate-induced increases in norepinephrine and dopamine levels in the
      preoptic area during the dark-phase may play an important role in modulating
      critical hypothalamic functions.

PMID- 19576880
TI  - In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies.
AB  - Amyloid-beta (Abeta) plaques are a pathological hallmark of Alzheimer's disease
      and a current target for positron emission tomography (PET) imaging agents.
      Whilst [(11)C]-PiB is currently the most widely used PET ligand in clinic, a
      novel family of benzoxazole compounds have shown promise as Abeta imaging agents;
      particularly BF227. We characterised the in vitro binding of [(18)F]-BF227 toward
      alpha-synuclein to address its selectivity for Abeta pathology, to establish
      whether [(18)F]-BF227 binds to alpha-synuclein/Lewy bodies, in addition to Abeta
      plaques. In vitro [(18)F]-BF227 saturation studies were conducted with 200 nM
      alpha-synuclein or Abeta(1-42) fibrils or 100 microg of Alzheimer's disease, pure
      dementia with Lewy bodies or control brain homogenates. Non-specific binding was
      established with PiB (1 microM). In vitro binding studies indicated that [(18)F]
      BF227 binds with high affinity to two binding sites on Abeta(1-42) fibrils (K(D1)
      = 1.31 and K(D2) = 80 nM, respectively) and to one class of binding sites on
      alpha-synuclein fibrils (K(D) = 9.63 nM). [(18)F]-BF227 bound to Abeta-containing
      Alzheimer's disease brain (K(D) = 25 +/- 0.5 nM), but failed to bind to Abeta
      free dementia with Lewy bodies or age-matched control homogenates. Moreover,
      BF227 labelled both Abeta plaques and Lewy bodies in
      immunohistochemical/fluorescence analysis of human Alzheimer's disease and
      Parkinson's disease brain sections, respectively. This study suggests that
      [(18)F]-BF227 is not Abeta-selective. Evaluation of BF227 as a potential
      biomarker for Parkinson's disease is warranted.

PMID- 19576881
TI  - Different antinociceptive effects of botulinum toxin type A in inflammatory and
      peripheral polyneuropathic rat models.
AB  - In addition to inhibition of acetylcholine release in the neuromuscular junction
      botulinum toxin type A (BoNT-A) also inhibits the release of mediators involved
      in pain perception. We have investigated the effect of two types of BoNT-A on
      mechanical hyperalgesia in the rat models of carrageenan-induced hyperalgesia and
      of paclitaxel-induced peripheral neuropathy. A subplantar (s.p.) injection of
      BoNT-A in the ipsilateral hindpaw 3 days before carrageenan administration
      reduced hypersensitivity. Dysport and Botox elicited comparable antihyperalgesic
      effects. Dysport up to 30 U/kg and Botox up to 20 U/kg did not impair the rat
      withdrawal nociceptive reflex or the locomotor performance as assessed by the
      rotarod test. Intraperitoneal administration of the skeletal muscle relaxant
      dantrolene produced, in contrast to BoNT-A, more motor impairment than analgesia.
      Paclitaxel treatment resulted in a peripheral neuropathy that affected the two
      hindpaws. Injection of 20 U/kg (s.p.) Dysport produced a significant
      antihyperalgesic effect in the injected paw of neuropathic animals 3 days after
      administration. Unexpectedly, a similar analgesic effect was observed in the
      contralateral paw. The same results were also observed when Botox was used
      instead of Dysport. In contrast, a contralateral administration of Dysport in the
      carrageenan test was ineffective. We conclude that BoNT-A elicits antinociceptive
      effects independent of the effects on muscular relaxation. Our results suggest
      that different mechanisms of action are responsible for the effect of BoNT-A in
      inflammatory and peripheral polyneuropathic rat models.

PMID- 19576882
TI  - Melatonin protects against alcoholic liver injury by attenuating oxidative
      stress, inflammatory response, and apoptosis.
AB  - Melatonin is reported to exhibit a wide variety of biological effects, including
      antioxidant and anti-inflammatory. Previous studies show that melatonin has a
      protective role in different types of liver injury and fibrosis. But its role in
      the pathogenesis of alcoholic liver injury remains obscure. The present
      investigation was designed to determine the effects of melatonin on alcohol
      induced hepatic injury in mice. The degree of alcoholic liver injury was
      evaluated by measuring serum markers and pathological examination. Treatment with
      melatonin significantly attenuated the increased level of serum aminotransferase,
      reduced the severe extent of hepatic cell damage, steatosis and the immigration
      of inflammatory cells, but had no effects on hepatic expression of lipogenic
      genes. Furthermore, melatonin decreased serum and tissue inflammatory cytokines
      levels, tissue lipid peroxidation, neutrophil infiltration and inhibited the
      apoptosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced
      high amounts of reactive oxygen species and tumor necrosis factor alpha, whereas
      Kupffer cells from melatonin treatment mice produced less reactive oxygen species
      and tumor necrosis factor alpha compared with model alcohol-feeding mice. These
      findings suggest that melatonin may represent a novel, protective strategy
      against alcoholic liver injury by attenuating oxidative stress, inflammatory
      response and apoptosis.

PMID- 19576883
TI  - Comparing the role of glutathione-S-transferase and mitochondrial aldehyde
      dehydrogenase in nitroglycerin biotransformation and the correlation with
      calcitonin gene-related peptide.
AB  - Both glutathione-S-transferase (GST) and mitochondrial aldehyde dehydrogenase
      (ALDH-2) have been reported to participate in the biotransformation of
      nitroglycerin. In this study, we explored which is the major player in
      nitroglycerin biotransformation. In vivo, rats were treated with nitroglycerin,
      the blood pressure and plasma calcitonin gene-related peptide (CGRP) were
      measured. The inhibitor of GST (ethacrynic acid) or ALDH-2 (cyanamide) was given
      before nitroglycerin treatment; In vitro, the isolated aorta rings were incubated
      with nitroglycerin to obtain the concentration-response curve. Ethacrynic acid or
      cyanamide was pre-incubated with the rings before nitroglycerin treatment. The
      release of CGRP from the aorta rings was determined. Both ethacrynic acid and
      cyanamide were able to reverse the depressant action of nitroglycerin while the
      inhibitory effect of cyanamide was more profound. However, combined
      administration of both inhibitors did not produce an additive effect. The change
      of plasma CGRP level positively correlated with the change of nitroglycerin
      induced hypotensive effects. In the isolated aorta rings, vasodilator responses
      to nitroglycerin were reduced in the presence of ethacrynic acid or cyanamide
      while the inhibitory effect of cyanamide was more profound. However, combined
      administration of both inhibitors did not produce an additive effect. The change
      of CGRP release from the rings positively correlated with the nitroglycerin
      induced vasodilator responses. The present results suggest that both GST and ALDH
      2 are involved in nitroglycerin action while ALDH-2 plays a major role, and the
      change of CGRP contents closely correlates with the biotransformation of
      nitroglycerin.

PMID- 19576884
TI  - Tanshinone II(A) elicited vasodilation in rat coronary arteriole: roles of nitric
      oxide and potassium channels.
AB  - Salvia miltiorrhiza has been widely used in the treatment of various
      cardiovascular diseases due to its ability to improve coronary microcirculation
      and increase coronary blood flow. Tanshinone II(A), the major active lipophilic
      ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was
      shown to induce vasodilation in coronary arteries. But its effects on coronary
      arterioles remain unknown. The purpose of this study was to investigate the
      effects of tanshinone II(A) on isolated rat coronary arteriole and the underlying
      mechanisms. Coronary arterioles were carefully dissected, cannulated and
      pressurized. Tanshinone II(A)-elicited vascular inner diameter change was
      recorded by a computerized diameter tracking system. To investigate the
      mechanisms governing the vasodilative effects of tanshinone II(A), the roles of
      endothelium, endothelium-derived vasoactive factors and potassium channels were
      assessed respectively. Endothelium denudation, inhibition of nitric oxide
      synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of
      the large conductance calcium(Ca(2+))-activated potassium channels (BKca)
      significantly decreased the vasodilation elicited by Tanshinone II(A). The
      results indicated that tanshinone II(A) induces an endothelium-dependent
      vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450
      metabolites contribute to the vasodilation; activation of BKca channels plays an
      important role in the vasodilation.

PMID- 19576886
TI  - Involvement of NADPH oxidase and protein kinase C in endothelin-1-induced
      superoxide production in retinal microvessels.
AB  - Redox signaling has been implicated in pathophysiological changes in the vascular
      system. We examined whether endothelin-1 (ET-1) increases the formation of
      superoxide anions in retinal microvessels. Freshly isolated retinal microvessels
      from rats were exposed to ET-1 (100 nM), and the intracellular superoxide
      formation in the retinal pericytes was assessed semi-quantitatively by time-lapse
      fluorometric analyses using hydroethidine. The receptor mechanisms were
      determined by BQ-123 and BQ-788, receptor antagonists for ET(A) and ET(B)
      receptors, respectively, and also by IRL-1620, a selective agonist for ET(B)
      receptors. In addition, the changes induced by adding apocynin (10 microM), myr
      PKC (1.0 microM), allopurinol (100 microM), rotenone (10 microM), or L-NAME (100
      microM) with ET-1 were evaluated. Microvessels were incubated with phorbol 12
      myristate 13-acetate (PMA, 10nM), a protein kinase C (PKC) activator.
      Fluorometric analyses showed ethidium fluorescence-positive regions that
      coincided well with the location of retinal pericytes. The intracellular
      superoxide levels were significantly increased after addition of ET-1 (100 nM),
      and this elevation was suppressed by apocynin or myr-PKC. Other enzyme inhibitors
      including L-NAME had no effect. The ET-1-induced increase of superoxide was
      significantly suppressed by BQ-123 (1.0 microM), while effects of adding BQ-788
      (1.0 microM) were insignificant. IRL-1620 (100 nM) did not increase superoxide
      formation significantly. PMA (10nM) mimicked the effect of ET-1. These results
      suggest that ET-1 increases the formation of superoxides in the retinal
      microvascular pericytes most likely by activating NADPH oxidase through ET(A)
      receptors. The activation of PKC may be involved in the mechanism. Thus, ET-1 may
      augment its vasoconstrictive effects through the formation of superoxide, which
      may impair the bioavailability of nitric oxide in the retinal microvasculature.

PMID- 19576887
TI  - Tissue kallikrein protects cortical neurons against in vitro ischemia
      acidosis/reperfusion-induced injury through the ERK1/2 pathway.
AB  - Human tissue kallikrein (hTK) gene transfer has been shown to protect neurons
      against cerebral ischemia/reperfusion (I/R) injury, and exogenous tissue
      kallikrein (TK) administration can enhance neurogenesis and angiogenesis
      following focal cortical infarction. Previous studies have reported that acidosis
      is a common feature of ischemia and plays a critical role in brain injury.
      However, little is known about the role of TK in ischemia-acidosis-induced
      injury, which is partially caused by the activation of acid-sensing ion channels
      (ASICs). Here we report that pretreatment of cultured cortical neurons with TK
      reduced cell death induced by either acidosis or oxygen and glucose deprivation
      acidosis/reoxygenation (OGD-A/R). Immunocytochemical staining revealed that TK
      largely prevented OGD-A/R-induced neuronal morphological changes. We also
      observed that TK treatment protected cultured neurons from acidosis and OGD-A/R
      insults. TK exerted the neuroprotective effects by reducing production of
      reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential
      (MMP) and inhibiting caspase-3 activation, and thereby attenuating oxidative
      stress and apoptosis. In addition, we found that activation of the extracellular
      signal-regulated kinase1/2 (ERK1/2) signaling cascade but not the PI3K/Akt
      signaling pathway was required for the survival-promoting effect of TK on neurons
      exposed to OGD-A/R. Moreover, blockade of ASICs had effects similar to TK
      administration, suggesting direct or indirect involvement of ASICs in TK
      protection. In conclusion, TK has antioxidant characteristics and is capable of
      alleviating ischemia-acidosis/reperfusion-induced injury, inhibiting apoptosis
      and promoting cell survival in vitro through activating the ERK1/2 signaling
      pathways. Therefore, TK represents a promising therapeutic strategy for ischemic
      stroke.

PMID- 19576888
TI  - GIF-0173 protects against cerebral infarction through DP1 receptor activation.
AB  - The neuroprotective effects and mechanism of action of GIF-0173, a Delta12
      prostaglandin J analogue, were investigated in the early phase of cerebral
      ischemia. GIF-0173 was administered intravenously immediately following middle
      cerebral artery occlusion (MCAO) in photochemically induced thrombosis model of
      rat. Neurological scores and infarct sizes were examined at 24 h after MCAO.
      Cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry for 1 h after
      MCAO. In cultured cortical neurons obtained from 1-day-old rats, the effects of
      GIF-0173 on the excitotoxicity induced by glutamate were examined. Morphological
      changes, neuronal death, and changes in intracellular calcium concentration
      ([Ca(2+)](i)) were also examined. GIF-0173 improved neurological scores and
      reduced the infarct size in a dose-dependent manner following MCAO. But GIF-0173
      did not improve CBF after MCAO. GIF-0173 also prevented glutamate-induced
      neuronal death and acute cellular swelling in primary cultures in a dose
      dependent manner, indicating that it inhibited neuronal necrosis. GIF-0173 dose
      dependently suppressed the glutamate-induced increase in [Ca(2+)](i), but could
      not inhibit NMDA-induced calcium influx. The effects of GIF-0173 against
      glutamate-induced [Ca(2+)](i) increase were reversed by addition of non-specific
      prostaglandin D (PGD(2)) receptor antagonist and were comparable to the effects
      of PGD(2) DP1 receptor agonist, which prevented [Ca(2+)](i) increase and neuronal
      death. We conclude that GIF-0173 reduces cerebral infarction and protects
      cultured neurons against glutamate-induced excitotoxicity by inhibiting
      [Ca(2+)](i) increase through DP1 receptor activation.

PMID- 19576885
TI  - Adenylate cyclase regulates elongation of mammalian primary cilia.
AB  - The primary cilium is a non-motile microtubule-based structure that shares many
      similarities with the structures of flagella and motile cilia. It is well known
      that the length of flagella is under stringent control, but it is not known
      whether this is true for primary cilia. In this study, we found that the length
      of primary cilia in fibroblast-like synoviocytes, either in log phase culture or
      in quiescent state, was confined within a range. However, when lithium was added
      to the culture to a final concentration of 100 mM, primary cilia of synoviocytes
      grew beyond this range, elongating to a length that was on average approximately
      3 times the length of untreated cilia. Lithium is a drug approved for treating
      bipolar disorder. We dissected the molecular targets of this drug, and observed
      that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked
      the effects of lithium on primary cilium elongation. Inhibition of GSK-3beta by
      four different inhibitors did not induce primary cilia elongation. ACIII was
      found in primary cilia of a variety of cell types, and lithium treatment of these
      cell types led to their cilium elongation. Further, we demonstrate that different
      cell types displayed distinct sensitivities to the lithium treatment. However, in
      all cases examined primary cilia elongated as a result of lithium treatment. In
      particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human
      astrocytes, developed long primary cilia when lithium was used at or close to the
      therapeutic relevant concentration (1-2 mM). These results suggest that the
      length of primary cilia is controlled, at least in part, by the ACIII-cAMP
      signaling pathway.

PMID- 19576889
TI  - Neuroprotective effect of transcorneal electrical stimulation on light-induced
      photoreceptor degeneration.
AB  - Direct electrical stimulation of neural tissues is a strategic approach to treat
      injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M.,
      Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed
      and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602-2608] and
      promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al
      Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron
      regeneration and growth-associated gene expression. Exp. Neurol. 205, 347-359].
      Recently, transcorneal electrical stimulation (TCES), a novel less invasive
      method, has been shown to rescue axotomized and damaged retinal ganglion cells
      [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y.,
      2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion
      cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis.
      Sci. 46(6), 2147-2155]. Here, we investigated the neuroprotection of TCES on
      light-induced photoreceptor degeneration and the underlying mechanism. Adult male
      Sprague-Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES)
      intense light exposure. After fourteen days of light exposure, retinal histology
      and electroretinography were performed to evaluate the neuroprotective effect of
      TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2,
      Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived
      neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and
      Western blot analysis. The localization of these gene products in the retinas was
      examined by immunohistochemistry. Both pre- and post-TCES ameliorated the
      progressive photoreceptor degeneration. The degree of rescue depended on the
      strength of the electric charge. Post-TCES showed a relatively better and longer
      term protective effect than pre-TCES. Real-time PCR and Western blot analysis
      revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in
      the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF
      were selectively upregulated in Muller cells. These findings provide a new
      therapeutic method to prevent or delay photoreceptor degeneration through
      activating the intrinsic survival system.

PMID- 19576890
TI  - Drug/nutrition interaction in the developing brain: dipyrone enhances spreading
      depression in rats.
AB  - The abuse of pharmaceutical drugs and the inadequate ingestion of nutrients
      constitute external factors that can alter brain development, both individually
      and in combination. We used cortical spreading depression (CSD) as a
      neurophysiological parameter to investigate the combined effects of the
      antipyretic/analgesic/anti-inflammatory drug dipyrone and malnutrition (M) in the
      developing rat brain. Suckling malnourished rats (M; n=69) and well nourished
      controls (W; n=76) received dipyrone (300 mg/kg/day) or saline per gavage for 7
      consecutive days during the 2nd, 3rd, or 4th postnatal week. At 35-45 days, CSD
      was recorded at 2 points in the parietal region. In both groups, dipyrone
      increased CSD propagation velocities compared to respective saline controls
      (P<0.05). This effect was intensified when dipyrone application during the 4th
      postnatal week intensified the increase compared to the 2nd and 3rd weeks. In
      saline-treated groups, the velocities (mean+/-s.d., in mm/min) were 3.70+/-0.11,
      3.77+/-0.16, and 3.78+/-0.13 (W) and 4.13+/-0.10, 4.16+/-0.10, and 4.14+/-0.09
      (M), for animals treated in the 2nd, 3rd and 4th postnatal weeks. In dipyrone
      treated groups, the respective values were 3.99+/-0.14, 4.03+/-0.16, and 4.30+/
      0.19 (W) and 4.47+/-0.17, 4.70+/-0.31, and 5.01+/-0.28 (M). Results support the
      hypothesis that dipyrone has a CSD-facilitating effect, which is more intense at
      a late brain developmental stage and is facilitated by malnutrition. This may
      help explain the developmental brain excitability changes that are associated
      with pharmacological and nutritional factors.

PMID- 19576892
TI  - Expression of ephrinA5 during development and potential involvement in the
      guidance of the mesostriatal pathway.
AB  - Identifying guidance cues that direct axon growth to their final connections
      during development is of crucial interest if we aim to repair circuits damaged in
      adulthood following neurodegenerative disorders or common traumatic injuries. In
      this work, we set out to determine the ephrinA5 guidance molecule involvement in
      the establishment of the mouse mesostriatal pathway during development. We
      showed, in vitro and in vivo, that a proportion of mesencephalic dopaminergic
      cells express the ephrinA5 receptor, EphA5. Moreover, we observed, using stripe
      assays, that ephrinA5 purified protein has a repulsive effect on most of the
      mesencephalic dopaminergic projections. In vivo, we detected rostro-caudal and
      ventro-dorsal ephrinA5 protein expression gradients in the vicinity of the
      dopaminergic axons in the ventral telencephalon and in the striatum, during the
      embryonic and early postnatal development. In addition, other EphA5 ligands were
      also detected in the mesostriatal pathway. Together, these expression patterns
      suggest that, ephrinAs and more specifically ephrinA5, may be actors in the
      guidance of dopaminergic projections. Further studies will focus on identifying
      the molecular specificity of these guidance cues, taking into account the
      mesencephalic dopaminergic heterogeneous neuronal population. This may help
      increase the integration of neuronal transplants in the mature lesioned brain or
      provide tools to re-establish mesostriatal circuits in vivo.

PMID- 19576893
TI  - Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation.
AB  - NFATc1 is a master regulator of RANKL-induced osteoclast differentiation and
      herein we investigate the regulatory mechanism of NFATc1 in osteoclast
      activation. Inactivation of NFATc1 strongly attenuates RANKL-induced bone
      resorption and overexpression of a constitutively active form of NFATc1 in
      osteoclasts induces formation of actin rings and resorption pits on dentin
      slices. We demonstrate that NFATc1 binds directly to the promoter regions of its
      target genes and induces expression of various genes, including LTBP3, ClC7,
      cathepsin K, MMP9, and c-Src, which are key players in bone resorption. Thus,
      NFATc1 is essential for RANKL-induced osteoclast activation via up-regulation of
      osteoclast-activating genes.

PMID- 19576891
TI  - Differential expression and potential role of SOCS1 and SOCS3 in Wallerian
      degeneration in injured peripheral nerve.
AB  - Pro-inflammatory chemokines and cytokines play an important role in Wallerian
      degeneration (WD) after peripheral nerve injury. These pro-inflammatory signals
      are "turned-off" in a timely manner to ensure that the inflammatory response in
      the injured nerve is limited. The factors that regulate the turning-off of the
      pro-inflammatory state are not fully understood. The suppressors of cytokine
      signaling (SOCS) proteins are potential candidates that could limit the
      inflammatory response by acting to regulate cytokine signaling at the
      intracellular level. In this work we show that the expression SOCS1 and SOCS3
      proteins differ from each other during WD in the mouse sciatic nerve after
      cut/ligation and crush injuries. SOCS1 is mainly expressed by macrophages and its
      expression is inversely correlated with phosphorylation of JAK2 and STAT3
      signaling proteins and the expression of pro-inflammatory cytokines IL-1beta and
      TNFalpha. In addition, treatment of cut/ligated nerves, which express lower
      levels of SOCS1 as compared to crush injury, with a SOCS1 mimetic peptide leads
      to a decrease in macrophage numbers at 14 days post-injury and reduces IL-1beta
      mRNA expression 1 day post-injury. In contrast, SOCS3 expression is restricted
      mainly to Schwann cells and is negatively correlated with the expression of IL-6
      and LIF. These data suggest that SOCS1 and SOCS3 may play different roles in WD
      and provide a better understanding of some of the potential regulatory mechanisms
      that may control inflammation and regeneration in the injured peripheral nerve.

PMID- 19576894
TI  - Electric dipole reorientation in the interaction of botulinum neurotoxins with
      neuronal membranes.
AB  - Botulinum neurotoxins are highly potent toxins capable of rapid and specific
      interaction with the presynaptic membrane. We have hypothesised that: (1) these
      neurotoxins possess an electric dipole with the positive pole on receptor binding
      domain Hc-C and that (2) on approaching the negatively charged presynaptic
      membrane, they reorient themselves and hit the membrane surface with Hc-C; this
      electrostatic effect would contribute efficient binding. Electrostatic
      calculations confirm these hypotheses and strongly indicate that electrostatics
      effects can play an important role in the unique presynaptic membrane binding
      properties of these neurotoxins and generally on the interaction of other plasma
      membrane protein ligands.

PMID- 19576895
TI  - Expression analysis of steroid hormone receptor mRNAs during zebrafish
      embryogenesis.
AB  - We have analyzed by qRT-PCR and/or RT-PCR the abundance and degradation rate of
      maternal mRNAs for nine steroid hormone receptors and their possible replacement
      by corresponding embryonic transcripts in both ovulated oocytes and embryos of
      zebrafish collected at 0, 1, 2, 4, 8, 12, 24 and 48 h post-fertilization (hpf).
      The mRNAs encoded the nuclear receptors for progesterone (pr), androgen (ar),
      estrogen (er alpha, er beta 1 and er beta 2), glucocorticoids (gr),
      mineralocorticoids (mr) and the membrane progestin receptor-alpha and beta (mpr
      alpha and beta). gr mRNA was the most abundant maternal transcript in oocytes and
      early embryos followed by er beta 2 and ar mRNAs. They declined during the first
      8 hpf, being replaced, thereafter, by the embryonic messengers. er beta 1 and mr
      transcript levels were low until 8 hpf, but increased steadily during embryonic
      transcription from 24 to 48 hpf. pr transcripts were detectable only in ovulated
      oocytes and at 24 and 48 hpf. At these stages, there was a slight increase of er
      alpha mRNA that initially was very low. mPr alpha and beta mRNAs were expressed
      in ovulated oocytes and faintly persisted during the first 4 hpf. There was no
      subsequent embryonic expression of these transcripts. The possible involvement of
      maternal mRNAs for glucocorticoid and sex hormone receptors in the programming of
      early zebrafish development is intriguing, since they mainly occur at stages in
      which gene replication predominates over transcription.

PMID- 19576897
TI  - Sand goby (Pomatoschistus minutus) males exposed to an endocrine disrupting
      chemical fail in nest and mate competition.
AB  - Endocrine disrupting chemicals (EDCs) are a widely studied group of chemicals
      that interfere with the endocrinology of organisms. So far, few studies have
      demonstrated the effect of EDCs on the reproductive behavior of aquatic wildlife.
      Here we show that sand goby males' (Pomatoschistus minutus) success in mating
      competition greatly decreases after an exposure for 7 to 24 days to 17alpha
      ethinyl estradiol (EE2, measured concentration 4 ng L(-1)). The sand goby
      exhibits a polygynous mating system with male parental care, in which males
      compete for nest sites and females. The aim of this study was to test how EE2
      exposure affects the ability of males to compete for breeding resources, i.e.
      nest sites and mates. First, EE2 exposed males competed over a nest site against
      a non-exposed, control male of the same size. Secondly, we examined male
      courtship behavior and female mate preferences for EE2 exposed males and similar
      sized non-exposed, control males. In addition to the behavioral experiments we
      determined the zona radiata protein (Zrp) mRNA gene expression and measured
      morphometric indicators of sexual maturation. Our study revealed that EE2 treated
      males were not able to acquire or defend a nest site. Additionally, EE2 treated
      males spent significantly less time in active courtship and nest leading behavior
      than control males. As a result, females clearly preferred to mate with control
      males. However, we found no significant differences in Zrp mRNA expression or the
      morphometric indicators between treatments. Our study illustrates that exposure
      to this EDC can greatly reduce the chances of an individual reproducing
      successfully. Moreover, it demonstrates that severe behavioral effects can be
      seen before any effects are detectable at the molecular or morphometric level.

PMID- 19576898
TI  - Techniques for time-efficient isolation of human skin dendritic cell subsets and
      assessment of their antigen uptake capacity.
AB  - Dendritic cells (DCs) residing in skin are important sentinels for foreign
      antigens. Methods to facilitate studies of subsets of skin DCs are important to
      increase the understanding of various pathogens, allergens, topical treatments or
      vaccine components targeting the skin. In this study, we developed a new DC
      purification method using a skin graft mesher, clinically used for expansion of
      skin grafts, to accelerate processing of skin into nets that allowed efficient
      enzymatic disruption and single cell isolation. The reduction in processing time
      using the skin graft mesher enabled processing of larger skin samples and also
      limited the ex vivo handling of the specimens which is associated with maturation
      of DCs. In addition, a skin explant model to functionally monitor early events of
      antigen uptake by DC subsets in situ was developed. DCs isolated from epidermis
      represented a uniform CD1a(+) HLA-DR(+) CD11c(+) Langerin(+) DC-SIGN(-) DC
      LAMP(int) DEC-205(int) Langerhans cell (LC) population whereas three subtypes of
      HLA-DR(+) CD11c(+) DCs were isolated from dermis based on their varying
      expression of CD1a. Epidermal LCs showed a significantly higher antigen uptake
      capacity of fluorescently-labelled ovalbumin (OVA) and dextran as compared to any
      of the dermal DC (dDC) subsets. In contrast, injection of antigen directly into
      skin explants followed by in situ imaging revealed that the majority of DCs with
      internalized antigen were localized in the dermis, likely as a consequence of the
      anatomical site for antigen delivery. These methods offer potency for various
      applications addressing antigen uptake, microbial DC interactions or other
      antigenic stimulation targeting the skin and can enhance our knowledge of basic
      DC biology in human skin.

PMID- 19576896
TI  - Tamoxifen produces conditioned taste avoidance in male rats: an analysis of
      microstructural licking patterns and taste reactivity.
AB  - Estrogen receptor activation has been shown to reduce body weight and produce a
      conditioned reduction in food intake in male rats that is putatively mediated by
      estradiol's suggested aversive effects. Evidence has shown that the selective
      estrogen receptor modulator tamoxifen used in the prevention and treatment of
      breast cancer may also produce changes in food intake and body weight, which are
      known to impact cancer development and survival. The purpose of the present study
      was to examine whether tamoxifen produces a conditioned reduction in intake
      similar to estradiol by producing a conditioned aversion. A one bottle lickometer
      test was used to examine conditioned changes in sucrose drinking, while the taste
      reactivity test was used to measure rejection reactions, which serve to index
      aversion in rats. A backward conditioning procedure that consisted of 3
      conditioning days and one vehicle test day was used to examine conditioned
      changes in 0.3 M sucrose intake and taste reactivity. Our results show that
      tamoxifen produced a conditioned reduction in sucrose drinking in a one bottle
      fluid intake test that was similar to the effects produced by estradiol (positive
      control); however, no active rejection reactions were produced by either
      tamoxifen (1 and 10 mg/kg) or estradiol. The present results suggest that
      tamoxifen, at the doses used in the present study, acts as an estrogen receptor
      agonist to regulate food intake and that the conditioned reduction in intake
      produced by tamoxifen and estradiol reflects conditioned taste avoidance rather
      than conditioned taste aversion.

PMID- 19576899
TI  - Quantification of amyloid-beta 40 in cerebrospinal fluid.
AB  - BACKGROUND: Truncated forms and full-length forms of the amyloid-beta 40
      (Abeta40) are key molecules in the pathogenesis of dementia, and are detectable
      in CSF. Reliable methods to detect these biomarkers in CSF are of great
      importance for understanding the disease mechanisms and for diagnostic purposes.
      METHODS: VU-alpha-Abeta40, a monoclonal antibody (mAb) specifically detecting
      Abeta40, was generated and characterized by solid and fluid phase ELISA, surface
      plasmon resonance spectroscopy (SPRS), immunoprecipitation (IP),
      immunohistochemical and Western blot (WB) analysis. In addition, an ELISA with VU
      alpha-Abeta40 as catching and 6E10 as detecting mAbs was set up and validated.
      This ELISA was used to measure Abeta40 in CSF of controls (N=27), patients with
      Alzheimer's disease (AD; N=20), frontotemporal lobe dementia (FTLD; N=14),
      noninflammatory (N=15) and inflammatory (N=15) neurological conditions. RESULTS:
      VU-alpha-Abeta40 specifically recognizes Abeta40 with high affinity
      (K(A)=1.3x10(9) M(-1)) and detects Abeta40 in AD brain specimens. The developed
      sandwich ELISA has a detection limit of 0.21 ng/mL, a mean recovery of 90%, and
      an intra- and inter-assay CV of 1.4% and 7.3%. FTLD patients had a lower mean
      level of Abeta40 (8.8 (1.9) ng/mL) than controls (12.0 (1.7) ng/mL); p<0.01).
      CONCLUSIONS: VU-alpha-Abeta40 was successfully implemented in an ELISA which
      enables us to measure Abeta40 accurately in human CSF. Clinical validation
      revealed lower levels of Abeta40 in FTLD patients. This finding opens new
      possibilities for early and differential diagnosis of dementia.

PMID- 19576900
TI  - Negative immunomagnetic selection of T cells from peripheral blood of
      presentation AML specimens.
AB  - To date, studies on T cells in acute myeloid leukemia (AML) have been limited to
      flow cytometric analysis of whole peripheral blood mononuclear cell (PBMC)
      specimens or functional work looking at the impact of AML myeloblasts on normal
      or remission T cells. This lack of information on T cells at the time of
      presentation with disease is due in part to the difficulty in isolating
      sufficiently pure T cells from these specimens for further study. Negative
      immunomagnetic selection has been the method of choice for isolating immune cells
      for functional studies due to concerns that binding antibodies to the cell
      surface may induce cellular activation, block ligand-receptor interactions or
      result in immune clearance. In order specifically to study T cells in
      presentation AML specimens, we set out to develop a method of isolating highly
      pure CD4 and CD8 T cells by negative selection from the peripheral blood (PB) of
      newly diagnosed AML patients. This technique, unlike T cell selection from PB
      from normal individuals or from patients with chronic lymphocytic leukaemia, was
      extremely problematic due to properties of the leukaemic myeloblasts. A
      successful method was eventually optimized requiring the use of a custom antibody
      cocktail consisting of CD33, CD34, CD123, CD11c and CD36, to deplete myeloblasts.

PMID- 19576901
TI  - The limited role of nonnative contacts in the folding pathways of a lattice
      protein.
AB  - Models of protein energetics that neglect interactions between amino acids that
      are not adjacent in the native state, such as the Go model, encode or underlie
      many influential ideas on protein folding. Implicit in this simplification is a
      crucial assumption that has never been critically evaluated in a broad context:
      Detailed mechanisms of protein folding are not biased by nonnative contacts,
      typically argued to be a consequence of sequence design and/or topology. Here we
      present, using computer simulations of a well-studied lattice heteropolymer
      model, the first systematic test of this oft-assumed correspondence over the
      statistically significant range of hundreds of thousands of amino acid sequences
      that fold to the same native structure. Contrary to previous conjectures, we find
      a multiplicity of folding mechanisms, suggesting that Go-like models cannot be
      justified by considerations of topology alone. Instead, we find that the crucial
      factor in discriminating among topological pathways is the heterogeneity of
      native contact energies: The order in which native contacts accumulate is
      profoundly insensitive to omission of nonnative interactions, provided that
      native contact heterogeneity is retained. This robustness holds over a
      surprisingly wide range of folding rates for our designed sequences. Mirroring
      predictions based on the principle of minimum frustration, fast-folding sequences
      match their Go-like counterparts in both topological mechanism and transit times.
      Less optimized sequences dwell much longer in the unfolded state and/or off
      pathway intermediates than do Go-like models. For dynamics that bridge unfolded
      and unfolded states, however, even slow folders exhibit topological mechanisms
      and transit times nearly identical with those of their Go-like counterparts. Our
      results do not imply a direct correspondence between folding trajectories of Go
      like models and those of real proteins, but they do help to clarify key
      topological and energetic assumptions that are commonly used to justify such
      caricatures.

PMID- 19576902
TI  - Dimer interface migration in a viral sulfhydryl oxidase.
AB  - Large double-stranded DNA viruses, including poxviruses and mimiviruses, encode
      enzymes to catalyze the formation of disulfide bonds in viral proteins produced
      in the cell cytosol, an atypical location for oxidative protein folding. These
      viral disulfide catalysts belong to a family of sulfhydryl oxidases that are
      dimers of a small five-helix fold containing a Cys-X-X-Cys motif juxtaposed to a
      flavin adenine dinucleotide cofactor. We report that the sulfhydryl oxidase
      pB119L from African swine fever virus (ASFV) uses for self-assembly surface
      different from that observed in homologs from mammals, plants, and fungi. Within
      a protein family, different packing interfaces for the same oligomerization state
      are extremely rare. We find that the alternate dimerization mode seen in ASFV
      pB119L is not characteristic of all viral sulfhydryl oxidases, as the flavin
      binding domain from a mimivirus sulfhydryl oxidase assumes the same dimer
      structure as the known eukaryotic enzymes. ASFV pB119L demonstrates the potential
      of large double-stranded DNA viruses, which have faster mutation rates than their
      hosts and the tendency to incorporate host genes, to pioneer new protein folds
      and self-assembly modes.

PMID- 19576903
TI  - Coupling molecular dynamics simulations with experiments for the rational design
      of indolicidin-analogous antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) have attracted much interest in recent years
      because of their potential use as new-generation antibiotics. Indolicidin (IL) is
      a 13-residue cationic AMP that is effective against a broad spectrum of bacteria,
      fungi, and even viruses. Unfortunately, its high hemolytic activity retards its
      clinical applications. In this study, we adopted molecular dynamics (MD)
      simulations as an aid toward the rational design of IL analogues exhibiting high
      antimicrobial activity but low hemolysis. We employed long-timescale, multi
      trajectory all-atom MD simulations to investigate the interactions of the peptide
      IL with model membranes. The lipid bilayer formed by the zwitterionic 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine (POPC) was chosen as the model erythrocyte
      membrane; lipid bilayers formed from a mixture of POPC and the negatively charged
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol were chosen to model bacterial
      membranes. MD simulations with a total simulation time of up to 4 micros revealed
      the mechanisms of the processes of IL adsorption onto and insertion into the
      membranes. The packing order of these lipid bilayers presumably correlated to the
      membrane stability upon IL adsorption and insertion. We used the degree of local
      membrane thinning and the reduction in the order parameter of the acyl chains of
      the lipids to characterize the membrane stability. The order of the mixed 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/POPC lipid bilayer reduced
      significantly upon the adsorption of IL. On the other hand, although the order of
      the pure-POPC lipid bilayer was perturbed slightly during the adsorption stage,
      the value was reduced more dramatically upon the insertion of IL into the
      membrane's hydrophobic region. The results imply that enhancing IL adsorption on
      the microbial membrane may amplify its antimicrobial activity, while the degree
      of hemolysis may be reduced through inhibition of IL insertion into the
      hydrophobic region of the erythrocyte membrane. In addition, through simulations,
      we identified the amino acids that are most responsible for the adsorption onto
      or insertion into the two model membranes. Positive charges are critical to the
      peptide's adsorption, whereas the presence of hydrophobic Trp8 and Trp9 leads to
      its deeper insertion. Combining the hypothetical relationships between the
      membrane disordering and the antimicrobial and hemolytical activities with the
      simulated results, we designed three new IL-analogous peptides: IL-K7 (Pro7-
      >Lys), IL-F89 (Trp8 and Trp9-->Phe), and IL-K7F89 (Pro7-->Lys; Trp8 and Trp9-
      >Phe). The hemolytic activity of IL-F89 is considerably lower than that of IL,
      whereas the antimicrobial activity of IL-K7 is greatly enhanced. In particular,
      the de novo peptide IL-K7F89 exhibits higher antimicrobial activity against
      Escherichia coli; its hemolytic activity decreased to only 10% of that of IL. Our
      simulated and experimental results correlated well. This approach-coupling MD
      simulations with experimental design-is a useful strategy toward the rational
      design of AMPs for potential therapeutic use.

PMID- 19576904
TI  - Selection of small peptides, inhibitors of translation.
AB  - Identification of small molecular weight compounds targeting specific sites in
      the ribosome can accelerate development of new antibiotics and provide new tools
      for ribosomal research. We demonstrate here that antibiotic-size short peptides
      capable of inhibiting protein synthesis can be selected by using specific
      elements of ribosomal RNA as a target. The 'h18' pseudoknot encompassing residues
      500-545 of the small ribosomal subunit RNA was used as a target in screening a
      heptapeptide phage-display library. Two of the selected peptides could
      efficiently interfere with both bacterial and eukaryotic translation. One of
      these inhibitory peptides exhibited a high-affinity binding to the isolated small
      ribosomal subunit (K(d) of 1.1 microM). Identification of inhibitory peptides
      that likely target a specific rRNA structure may pave new ways for validating new
      antibiotic sites in the ribosome. The selected peptides can be used as a tool in
      search of novel site-specific inhibitors of translation.

PMID- 19576905
TI  - Molecular mechanisms regulating urogenital expression of nitric oxide synthase in
      spontaneously hypertensive rats.
AB  - AIMS: Although doxazosin, but not nifedipine, can partially prevent a decrease in
      urogenital expression of nitric oxide synthase (NOS) in spontaneously
      hypertensive rats (SHRs), the mechanisms involved in the regulated expression of
      NOS are not known. Therefore, we identified differential gene expression profiles
      in SHRs to elucidate the molecular mechanisms regulating urogenital expression of
      NOS. MAIN METHODS: SHRs and normotensive Wistar-Kyoto (WKY) rats received
      doxazosin (30 mg/kg/day) or nifedipine (30 mg/kg/day) orally for 4 weeks.
      Microarray expression data of key transcripts were verified by real-time reverse
      transcription-polymerase chain reaction (RT-PCR) analysis. KEY FINDINGS: RT-PCR
      data, in accord with the microarray analysis, indicated that untreated SHRs had
      lower mRNA expression levels of cAMP responsive element binding protein 1 (Creb1)
      in the pelvic ganglion and vascular endothelial growth factor A (Vegfa) and
      kinase insert domain protein receptor (Kdr) in the penis, and higher mRNA
      expression levels of brain derived neurotrophic factor and neurotrophin 3 (Ntf3)
      in the bladder and Ntf3, Rho-kinases (Rock1 and Rock2) and caveolin 1 (Cav1) in
      the penis than untreated WKY rats. In SHRs, doxazosin and nifedipine caused a
      significant decrease in penile expression of Rock1 and Rock2, whereas the
      differential alterations in urogenital expression of Creb1, Vegfa, Kdr and Cav1
      were attenuated by treatment with doxazosin, but not nifedipine. SIGNIFICANCE:
      Our data suggest that differential alterations in the expression of several genes
      related to pathways that mediate NOS expression in the urogenital tissues of
      SHRs, which can be attenuated by doxazosin treatment, may play an important role
      in regulating urogenital expression of NOS.

PMID- 19576906
TI  - Micronutrient prenatal supplementation prevents the development of hypertension
      and vascular endothelial damage induced by intrauterine malnutrition.
AB  - AIMS: The premise that intrauterine malnutrition plays an important role in the
      development of cardiovascular and renal diseases implies that these disorders can
      be programmed during fetal life. Here, we analyzed the hypothesis that
      supplementation with mixed antioxidant vitamins and essential mineral in early
      life could prevent later elevation of blood pressure and vascular and renal
      dysfunction associated with intrauterine malnutrition. MAIN METHODS: For this,
      female Wistar rats were randomly divided into three groups on day 1 of pregnancy:
      control fed standard chow ad libitum; restricted group fed 50% of the ad libitum
      intake and a restricted plus micronutrient cocktail group treated daily with a
      combination of micronutrient (selenium, folate, vitamin C and vitamin E) by oral
      gavage. KEY FINDINGS: In adult offspring, renal function and glomerular number
      were impaired by intrauterine malnutrition, and the prenatal micronutrient
      treatment did not prevent it. However, increased blood pressure and reduced
      endothelium-dependent vasodilation were prevented by the micronutrient prenatal
      treatment. Intrauterine malnutrition also led to reduced NO production associated
      with increased superoxide generation, and these parameters were fully normalized
      by this prenatal treatment. SIGNIFICANCE: Our current findings indicate that
      programming alterations during fetal life can be prevented by interventions
      during the prenatal period, and that disturbance in availability of both
      antioxidant vitamins and mineral may play a crucial role in determining the
      occurrence of long-term cardiovascular injury.

PMID- 19576907
TI  - Sequential estimation for prescribed statistical accuracy in stochastic
      simulation of biological systems.
AB  - Stochastic simulation of biological systems proceeds by repeatedly generating
      sample paths or trajectories of the underlying stochastic process, from which
      many relevant and important system properties can be obtained. While a great deal
      of research is targeted towards accelerated trajectory generation, issues
      concerned with the variability across trajectories are often neglected. Advanced
      methods for properly quantifying the statistical accuracy and determining a
      reasonable number of trajectories are hardly addressed formally in the context of
      biological system simulation, though mathematical statistics provides a large
      body of powerful theory. We invoke this theory and show how mathematically well
      founded sequential estimation approaches serve for systematically generating
      enough but not too many trajectories for achieving a certain prescribed accuracy.
      The practical applicability is demonstrated and illustrated by numerical examples
      through simulation studies of an immigration-death process and a gene regulatory
      network.

PMID- 19576908
TI  - All that glisters is not galled.
AB  - Galled trees, evolutionary networks with isolated reticulation cycles, have
      appeared under several slightly different definitions in the literature. In this
      paper, we establish the actual relationships between the main four such
      alternative definitions: namely, the original galled trees, level-1 networks,
      nested networks with nesting depth 1, and evolutionary networks with arc-disjoint
      reticulation cycles.

PMID- 19576909
TI  - SP protects cerebellar granule cells against beta-amyloid-induced apoptosis by
      down-regulation and reduced activity of Kv4 potassium channels.
AB  - The tachykinin endecapeptide substance P (SP) has been demonstrated to exert a
      functional role in neurodegenerative disorders, including Alzheimer's disease
      (AD). Aim of the present study was to evaluate the SP neuroprotective potential
      against apoptosis induced by the neurotoxic beta-amyloid peptide (A beta) in
      cultured rat cerebellar granule cells (CGCs). We found that SP protects CGCs
      against both A beta(25-35)- and A beta(1-42)-induced apoptotic CGCs death as
      revealed by live/dead cell assay, Hoechst staining and caspase(s)-induced PARP-1
      cleavage, through an Akt-dependent mechanism. Since in CGCs the fast inactivating
      or A-type K(+) current (I(KA)) was potentiated by A beta treatment through up
      regulation of Kv4 subunits, we investigated whether I(KA) and the related
      potassium channel subunits could be involved in the SP anti-apoptotic activity.
      Patch-clamp experiments showed that the A beta-induced increase of I(KA) current
      amplitude was reversed by SP treatment. In addition, as revealed by Western blot
      analysis and immunofluorescence studies, SP prevented the up-regulation of Kv4.2
      and Kv4.3 channel subunits expression. These results indicate that SP plays a
      role in the regulation of voltage-gated potassium channels in A beta-mediated
      neuronal death and may represent a new approach in the understanding and
      treatment of AD.

PMID- 19576910
TI  - Effect of non-dopaminergic drug treatment on Levodopa induced dyskinesias in MPTP
      monkeys: common implication of striatal neuropeptides.
AB  - Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA)
      administration that induces dyskinesias are associated with an enhancement of
      basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic
      treatments to Levodopa were shown to reduce and/or prevent dyskinesias. The aim
      of this study was to seek if non-dopaminergic drug treatments to 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkeys combined with L-DOPA to
      prevent dyskinesia were associated with changes of striatal neuropeptides.
      Chronic treatment with Ro 61-8048 a kynurenine hydroxylase inhibitor,
      docosahexaenoic acid (DHA) a polyunsaturated fatty acid (omega-3), naltrexone an
      opioidergic antagonist and CI-1041 an N-methyl-D-aspartate (NMDA) glutamate
      receptor antagonist with L-DOPA prevented dyskinesias to various extents except
      naltrexone whereas all MPTP monkeys treated with L-DOPA alone developed
      dyskinesias. Striatal preproenkephalin (PPE), preprodynorphin (PPD) and
      preprotachykinin A (PPT-A) mRNA levels were measured by in situ hybridization. An
      increase of PPE and PPD mRNA levels was observed in anterior caudate nucleus of L
      DOPA treated MPTP monkeys compared to controls and to Saline-treated MPTP monkeys
      whereas PPT-A mRNA levels were unchanged. Striatal PPE and PPD mRNA levels
      remained elevated in L-DOPA plus naltrexone-treated MPTP monkeys, while co
      treatment with DHA, CI-1041 or Ro 61-8048 prevented their increase to various
      extents. Maximal dyskinesias scores of MPTP monkeys correlated significantly with
      striatal PPE and PPD mRNA levels but not with PPT-A mRNA levels. These results
      show that drugs displaying a wide range of pharmacological activities can
      modulate L-DOPA induced dyskinesias and this activity is correlated with striatal
      PPD and PPE mRNA levels suggesting a convergent mechanism.

PMID- 19576911
TI  - Neuropeptide S attenuates neuropathological, neurochemical and behavioral changes
      induced by the NMDA receptor antagonist MK-801.
AB  - Neuropeptide S (NPS) and its cognate receptor were reported to mediate anxiolytic
      like and arousal effects. NPS receptors are predominantly expressed in the brain,
      especially in limbic structures, including amygdala, olfactory nucleus, subiculum
      and retrosplenial cortex. In contrast, the NPS precursor is expressed in only a
      few brainstem nuclei where it is co-expressed with various excitatory
      transmitters, including glutamate. The current study investigates interactions of
      the NPS system with glutamatergic neurotransmission. It has been suggested that
      dysfunctions in glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA)
      receptors might be involved in the pathophysiology of schizophrenia since NMDA
      receptor antagonists, such as MK-801, have been shown to induce psychotic-like
      behavior in humans and animal models. Also, MK-801 is known to produce
      histological changes such as cytoplasmic vacuoles in retrosplenial cortex neurons
      where NPS receptors are highly expressed. In this study we show that NPS is able
      to alleviate neuropathological, neurochemical and behavioral changes produced by
      NMDA receptor antagonists. NPS treatment attenuated MK-801-induced vacuolization
      in the rat retrosplenial cortex in a dose-dependent manner that can be blocked by
      an NPS receptor-selective antagonist. NPS also suppressed MK-801-induced
      increases of extracellular acetylcholine levels in the retrosplenial cortex. In
      the prepulse inhibition (PPI) assay, animals pretreated with NPS recovered
      significantly from MK-801-induced disruption of PPI. Our study suggests that NPS
      may have protective effects against the neurotoxic and behavioral changes
      produced by NMDA receptor antagonists and that NPS receptor agonists may elicit
      antipsychotic effects.

PMID- 19576913
TI  - Mass spectrometric profiling of (neuro)-peptides in the worker honeybee, Apis
      mellifera.
AB  - The honeybee is the economically most important beneficial insect and a model for
      studying immunity, development and social behavior. Hence, this species was
      selected for genome sequencing and annotation. An intensive interplay between
      bioinformatics and mass spectrometry (MS) resulted in the annotation of 36
      neuropeptide genes (Hummon et al., 2006). Exactly 100 peptides were demonstrated
      by a variety of MS techniques. In this follow-up study we dissected and analysed
      separately all ganglia of the central nervous system (CNS) of adult worker bees
      in three repeats. The combined MALDI-TOF spectra enabled the accurate mapping of
      67 peptides, encoded by 20 precursors. We also demonstrated the expression of an
      additional but already predicted peptide. In addition to putative bioactive
      peptides we also list and discuss spacer peptides, propeptides and truncated
      peptides. The majority of such peptides have a more restricted distribution
      pattern. Their presence provides some information on the precursor turnover
      and/or the location of neural cell bodies in which they are produced. Of a given
      precursor, the (neuro)-peptides with the widest distribution pattern are likely
      to be the best candidates to interact with receptors. The separate analysis of a
      neuroendocrine complex and the mushroom body yields suggestions as to which
      (neuro)-peptides might act as hormones and which neuropeptides might be involved
      in the complex spectrum of non-hormone driven honeybee behaviour, at these sites.
      Our data complement immunohistochemical studies of (neuro)-peptides in the
      honeybee, and form a reference for comparative studies in other insect or
      arthropod models, in particular in the light of recent or upcoming genome
      projects. Finally, they also form a firm basis for physiological, functional
      and/or differential peptidomics studies in the honeybee.

PMID- 19576912
TI  - Activation of somatostatin receptor (sst 5) protects the rat retina from AMPA
      induced neurotoxicity.
AB  - In a recent study, we employed an in vivo model of retinal excitotoxicity to
      investigate the neuroprotective effect of somatostatinergic agents. Intravitreal
      administration of somatostatin and sst(2) selective agonists protected the retina
      from (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide
      (AMPA) induced excitotoxicity. The sst(1) and sst(4) selective ligands had no
      effect (Kiagiadaki and Thermos, 2008). The presence of sst(5) receptors in rat
      retina was only recently reported (Ke and Zhong, 2007). Synthetic agonists that
      activate sst(2) receptors also bind with high affinity to the sst(5) subtype. In
      the present study the putative neuroprotective effects of sst(5) receptor
      activation were investigated. Adult female and male Sprague-Dawley (250-350g)
      rats were employed. Groups of animals received intravitreally PBS (50mM) or AMPA
      (42 nmol/eye) alone or in combination with L-817,818 (sst(5), 10(-5), 10(-4)M).
      To exclude neuroprotective effects via the activation of sst(2) receptors, L
      817,818 (10(-4)M) was coinjected with the sst(2) antagonist CYN-154806 (10(-4)M).
      Immunohistochemistry (IHC) studies using the anti-retinal marker choline
      acetyltransferase (ChAT) and TUNEL staining were employed to examine retinal cell
      loss and protection. IHC and Western blot analysis were also employed to assess
      whether the sst(5) receptors are viable in the AMPA treated tissue as compared to
      control retina. sst(5) receptors were not affected by AMPA. L-817,818 protected
      the retina from the AMPA insult in the dose of 10(-4)M, while CYN-154806 (10(
      4)M) had no effect on the sst(5) neuroprotection. TUNEL staining confirmed the
      AMPA-induced retinal toxicity and the L-817,818 neuroprotection. These results
      demonstrate for the first time that sst(5) receptors are functional in the
      retina, and that sst(5) analogs administered intravitreally protect the retina
      from excitotoxicity. Further studies are essential to ascertain the therapeutic
      relevance of these results.

PMID- 19576914
TI  - Intracerebroventricular infusion of bombesin modulates GIP secretion in conscious
      dogs.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is an incretin with important
      role in glucose homeostasis and energy conservation. Thus far, the neural
      mechanisms involved in the regulation of GIP secretion, have not yet been fully
      elucidated. The aim of this study was to evaluate a possible effect of
      intracerebroventricular administration of Bombesin in the regulation of GIP
      secretion. METHODS: Thirty-two adult dogs were used in this study. In group 1 the
      animals received a bolus icv infusion of 200 ng bombesin or an equivalent amount
      of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a
      continuous icv infusion of bombesin or aCSF over a 3-h period. In group 3 the
      experiment of group 2 was repeated with a simultaneous intraduodenal infusion of
      a glucose load through the Mann-Bollman fistula. Blood samples were taken from
      cannulation of a hind limb and plasma levels of glucose, insulin and GIP were
      assayed. RESULTS: Bolus icv infusion of bombesin produced an increase in glucose
      and GIP levels without a respective increase in plasma insulin levels. Continuous
      icv infusion and the simultaneous infusion of glucose intraduodenally increased
      significantly GIP, glucose and insulin levels. CONCLUSIONS:
      Intracerebroventricular levels of bombesin seems to involve in the neural
      regulation of GIP secretion independently of the presence of nutrients and to
      potentiate GIP secretion during a glucose load.

PMID- 19576916
TI  - Development of highly sensitive quantification method for testosterone and
      dihydrotestosterone in human serum and prostate tissue by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - We developed highly sensitive detection of testosterone (T) and 5alpha
      dihydrotestosterone (DHT) by liquid chromatography-electrospray ionization tandem
      mass spectrometry using high proton affinitive derivatization of 17beta-hydroxyl
      group of T and DHT with picolinic acid, mobile phase consisting of MeCN-MeOH
      H(2)O-formic acid and conventional octadecylsilica (ODS) column. Purification of
      the derivatives was carried out using solid-phase extraction with ODS cartridge.
      By this method, T and DHT were determined simultaneously with limits of
      quantification (LOQs) of 1 pg/0.2 ml in serum, and T and DHT with LOQs of 0.5 pg
      and 1 pg/3mg in prostate tissue, respectively, under acceptable assay performance
      (intra-assay and inter-assay accuracy and precision). The present method provides
      reliable and reproducible results for quantification of T and DHT in small
      volumes of serum and prostate samples for diagnosis in prostatic disorders and
      male climacteric.

PMID- 19576917
TI  - 3-Keto-22-epi-28-nor-cathasterone, a brassinosteroid-related metabolite from
      Cystoseira myrica.
AB  - Bioassay-guided purification of an ethanolic extract of Cystoseira myrica against
      HEPG-2 (liver) and HCT116 (colon) human cancer cell lines led to the isolation of
      3-keto-22-epi-28-nor-cathasterone, 1 and cholest-4-ene-3,6-dione, 2. This finding
      allowed us to report for the first time that a brassinosteroid-related metabolite
      occurs in seaweed. These compounds showed activity in the range of 12.38-1.16
      microM with selective activity of compound 2 to liver cancer cell lines.

PMID- 19576915
TI  - Long-term effects of provided low and high glycemic load low energy diets on mood
      and cognition.
AB  - Energy-restricted low glycemic load diets are being used increasingly for weight
      loss. However, the long-term effects of such regimens on mood and cognitive
      performance are not known. We assessed the effects of low glycemic load (LG) and
      high glycemic load (HG) energy-restricted diets on mood and cognitive performance
      during 6 months of a randomized controlled trial when all food was provided.
      Subjects were 42 healthy overweight adults (age 35+/-5 years; BMI 27.8+/-1.6
      kg/m(2)) with a mean weight loss of 8.7+/-5.0% that did not differ significantly
      by diet randomization. Mood was assessed by using the Profile of Mood States
      (POMS) questionnaire. Cognitive performance was assessed by using computerized
      tests of simple reaction time, vigilance, learning, short-term memory and
      attention, and language-based logical reasoning. Worsening mood outcome over time
      was observed in the HG diet group compared to the LG for the depression subscale
      of POMS (p=0.009 after including hunger as a covariate). There was no significant
      change over time in any cognitive performance values. These findings suggest a
      negative effect of an HG weight loss diet on sub-clinical depression but, in
      contrast to a previous suggestion, provide no support for differential effects of
      LG versus HD diets on cognitive performance.

PMID- 19576919
TI  - Methamphetamine induces heme oxygenase-1 expression in cortical neurons and glia
      to prevent its toxicity.
AB  - The impairment of cognitive and motor functions in humans and animals caused by
      methamphetamine (METH) administration underscores the importance of METH toxicity
      in cortical neurons. The heme oxygenase-1 (HO-1) exerts a cytoprotective effect
      against various neuronal injures; however, it remains unclear whether HO-1 is
      involved in METH-induced toxicity. We used primary cortical neuron/glia
      cocultures to explore the role of HO-1 in METH-induced toxicity. Exposure of
      cultured cells to various concentrations of METH (0.1, 0.5, 1, 3, 5, and 10 mM)
      led to cytotoxicity in a concentration-dependent manner. A METH concentration of
      5 mM, which caused 50% of neuronal death and glial activation, was chosen for
      subsequent experiments. RT-PCR and Western blot analysis revealed that METH
      significantly induced HO-1 mRNA and protein expression, both preceded cell death.
      Double and triple immunofluorescence staining further identified HO-1-positive
      cells as activated astrocytes, microglia, and viable neurons, but not dying
      neurons. Inhibition of the p38 mitogen-activated protein kinase pathway
      significantly blocked HO-1 induction by METH and aggravated METH neurotoxicity.
      Inhibition of HO activity using tin protoporphyrine IX significantly reduced HO
      activity and exacerbated METH neurotoxicity. However, prior induction of HO-1
      using cobalt protoporphyrine IX partially protected neurons from METH toxicity.
      Taken together, our results suggest that induction of HO-1 by METH via the p38
      signaling pathway may be protective, albeit insufficient to completely protect
      cortical neurons from METH toxicity.

PMID- 19576918
TI  - PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation
      of extracellular glutamate and intracellular calcium.
AB  - The human immunodeficiency virus (HIV-1) protein Tat has been implicated in
      mediating neuronal apoptosis, one of the hallmark features of HIV-associated
      dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential
      mechanism for reducing HIV toxicity in the brain. In this study we demonstrated
      that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting
      the role of glutamate in this process. Furthermore, we also found that
      pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity
      by decreasing extracellular glutamate levels. We also demonstrated that
      extracellular calcium chelator EGTA was able to abolish PDGF-mediated
      neuroprotection, thereby underscoring the role of calcium signaling in PDGF
      mediated neuroprotection. We also showed that Erk signaling pathway was critical
      for PDGF-mediated protection of cells. Additionally, blocking calcium entry with
      EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus
      underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in
      the protection of cells against HIV Tat toxicity.

PMID- 19576920
TI  - The phylum Cnidaria and investigations of its toxins and venoms until 1990.
AB  - Cnidarians are the largest phylum of generally toxic animals, yet their toxins
      and venoms have not received as much scientific attention as those of many
      terrestrial (snakes, scorpions, spiders, etc.) and even some marine animals (i.e.
      cone snails). Approximately 13,000 living cnidarian species have been described
      by systematists. A major rationale for their study in the past, besides
      scientific curiosity, was to better treat victims of their envenomation. While
      that goal remains a high priority, it is now appreciated that the toxins of these
      mostly marine animals can be very useful molecular probes for the analysis of ion
      channels involved in electrical signaling, immune responses and other signal
      transduction processes of biomedical interest. For instance, anaphylaxis was
      discovered by Richet (1905) during experiments with sea anemone and hydrozoan
      tentacular extracts. Similarly, it has recently been shown that a toxin from
      another sea anemone is able to potently inhibit T-lymphocyte proliferation in
      models of certain autoimmune diseases. Thus, these natural substances continue to
      be of relevance for understanding and treating human diseases. In addition to
      introducing phylum Cnidaria (Coelenterata), we provide a short history of early
      (until about 1990) research on cnidarian toxins and venoms, to provide a
      perspective for appreciating the scientific advances of the past two decades that
      are summarized in the ensuing 19 papers in this special Toxicon issue.

PMID- 19576921
TI  - Poisoning of sheep by seeds of Crotalaria retusa: acquired resistance by
      continuous administration of low doses.
AB  - Seeds of Crotalaria retusa containing 6.84% (dry weight) of monocrotaline (MCT)
      were administered experimentally to sheep. Three sheep that received 136.8mg
      MCT/kg bw daily for 70 days had no clinical signs. Five out of six sheep
      ingesting single doses of 205.2 and 273.6mg MCT/kg bw died with acute (three
      sheep) or chronic intoxication (two sheep). Acute intoxicated sheep had
      periacinar liver necrosis and chronic intoxicated sheep liver fibrosis and
      megalocytosis. Another three sheep had no clinical signs after the ingestion of
      20 daily doses of 136.8mg MCT/kg, followed by seven doses of 273.6mg MCT/kg, and
      one single dose of 342mg MCT/kg. These experiments demonstrated that sheep are
      susceptible to acute intoxication by MCT being intoxicated by a single oral dose
      of approximately 205.2mg/kg. In contrast, they develop strong resistance to MCT
      after the daily ingestion of non lethal doses (136.8mg/kg). It is suggested that
      chronic poisoning does not occur by the repeated ingestion of non acutely toxic
      doses, but probably by the ingestion of single toxic doses. It is also suggested
      that sheep do not become intoxicated with the ingestion of C. retusa in the
      vegetative non-seeding stage.

PMID- 19576922
TI  - Cnidarian toxins and venoms. Preface.

PMID- 19576923
TI  - Chronic periadolescent cannabinoid treatment enhances adult hippocampal PSA-NCAM
      expression in male Wistar rats but only has marginal effects on anxiety, learning
      and memory.
AB  - Pubertal and adolescent exposure to cannabinoids is associated with enduring
      alterations in anxiety and memory. However, periadolescence virtually remains
      unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult
      Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP
      55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p., 1 daily injection), and we also defined
      their recognition memory in the novel object paradigm and spatial learning and
      memory in the water maze. Additionally, we measured the expression of hippocampal
      PSA-NCAM (Polysialic Acid-Neural Cell Adhesion Molecule) and long-term
      potentiation (LTP) as well as, given their role in mnemonic processing, the
      levels of plasma corticosterone and estradiol. We found that CP had no robust
      effects on anxiety or in recognition memory. In the water maze, only a slight
      decreased percentage of failed trials in the reference memory task and an
      improvement in an indirect index of attention were observed. However, we detected
      an up-regulation of hippocampal PSA-NCAM expression, only in CP-males, although
      this effect was not related to changes in LTP. No hormonal alterations were
      evident. Based on our data, minimal long-term effects on anxiety, learning and
      memory appear to result from cannabinoid exposure during the periadolescent
      period.

PMID- 19576924
TI  - PRX-00023, a selective serotonin 1A receptor agonist, reduces ultrasonic
      vocalizations in infant rats bred for high infantile anxiety.
AB  - To address the development of early anxiety disorders across the lifespan, the
      High USV line of rats was bred based on rates of infant ultrasonic vocalization
      in the 40-50 kHz range of predominant frequencies (USV) to maternal separation at
      postnatal day (P) 10. In this study, rates of USV in High line infants (pups:
      Postnatal Day 11+/-1) were compared to those of randomly-bred controls in
      response to EPIX compound PRX-00023, a unique serotonin (5-HT) agonist, acting
      exclusively at the 5-HT1A receptor, or buspirone, a nonspecific 5HT1A agonist.
      After testing, pups were examined for sedation and other drug-related effects.
      The results indicated that all doses of buspirone reduced USV rates in isolation,
      consistent with other reports. PRX-00023 significantly reduced USV rates at the
      lowest doses (0.01-0.05 mg/kg). None of the PRX-00023 doses produced sedation,
      whereas all but the lowest dose of buspirone (0.1 mg/kg) produced sedation
      effects. The results suggest that this compound alleviates infantile anxiety-like
      behavior with great specificity in rats bred for high anxiety/depressive
      phenotypes by selectively targeting 5-HT1A receptors, possibly by both pre- and
      post-synaptic mechanisms.

PMID- 19576925
TI  - Socioeconomic status and risk factors for obesity and metabolic disorders in a
      population-based sample of adult females.
AB  - OBJECTIVES: The association between lower socioeconomic status (SES), obesity,
      lifestyle choices and adverse health consequences are well documented, however to
      date the relationship between these variables and area-based SES (equivalised for
      advantage and disadvantage) has not been examined simultaneously in one
      population or with more than tertiary divisions of SES. We set out to examine the
      risk factors for obesity and metabolic disorders in the same population across
      quintiles of area-based SES. METHODS: We performed a descriptive cross-sectional
      study using existing data from a population-based random selection of women aged
      20-92 years (n=1110) recruited from the Barwon Statistical Division, South
      Eastern Australia. RESULTS: All measures of adiposity were inversely associated
      with SES, and remained significant after adjusting for age. Lifestyle choices
      associated with adiposity and poorer health, including smoking, larger serving
      sizes of foods, and reduced physical activity, were significantly associated with
      individuals from lower SES groups. CONCLUSIONS: Greater measures of adiposity and
      less healthy lifestyle choices were observed in individuals from lower SES.
      Significant differences in body composition were identified between quintiles 1
      and 5, whereas subjects in the mid quintiles had relatively similar measures. The
      inverse relationship between SES, obesity and less healthy lifestyle underscores
      the possibility that these associations may be causal and should be investigated
      further.

PMID- 19576926
TI  - Personal and clinical tobacco-related practices and attitudes of U.S. medical
      students.
AB  - OBJECTIVES: Medical students' tobacco-related practices particularly matter
      because practicing physicians' smoking predicts their tobacco counseling; the
      objective of this study was to determine when this relationship between personal
      and clinical tobacco practices develops, and to determine predictors of medical
      students' personal smoking habits, and predictors of their patient tobacco
      counseling practices. METHODS: We surveyed the Class of 2003 between 1999 and
      2003, at freshman orientation (n=1836), entrance to wards (n=1616), and senior
      year (n=1441) in a nationally representative sample of 16 U.S. medical schools
      (response rate=80.3%). Tobacco use questions came from Centers for Disease
      Control and Prevention datasets, and tobacco counseling questions from validated
      instruments. RESULTS: 12% of female and 15% of male U.S. medical students report
      smoking, with no differences in usage over time. More tobacco counseling training
      and strongly believing in prevention significantly predicted both more perceived
      counseling relevance and frequency. Additionally, intention to practice primary
      care predicted relevance (OR=3.5, 95% CI: 2.5-4.9), and tobacco users were 77%
      (95% CI: 64%-94%) as likely as non-users to report frequently counseling smokers.
      CONCLUSIONS: U.S. medical students are less likely to smoke than other young U.S.
      adults, but more likely than U.S. physicians, and showed no clear decrease during
      medical school. It is encouraging that medical students with more exposure
      appreciate tobacco counseling's importance more, and are more likely to counsel.
      Students' personal tobacco use was also associated with counseling frequency.
      These data should help educators seeking better methods to reduce tobacco use.

PMID- 19576928
TI  - Promoting physical activity and healthy eating: convergence in framing the role
      of industry.
AB  - This commentary addresses a little explored aspect of prevention, namely, how
      public health practitioners conceptualize the roles of industries whose business
      interests may be at odds with physical activity and eating nutrient-rich foods.
      Taking their cues from successful campaigns in tobacco control, many public
      health advocates have framed obesity as a battle with the food industry. Such
      framing presents problems when it exacerbates existing tensions between
      practitioners in nutrition and physical activity, and alienates potential fitness
      industry partners. Creating healthy environments requires reframing expectations
      of all industries that influence physical activity and inactivity. A broader view
      of the influence of corporate practices on physical and social environments will
      help both physical activity and nutrition advocates identify what they can do
      together, and in partnership with the business sector, to create environments
      that promote activity and nutritious eating.

PMID- 19576927
TI  - Worksite Opportunities for Wellness (WOW): effects on cardiovascular disease risk
      factors after 1 year.
AB  - OBJECTIVE: To evaluate the effectiveness of a worksite health promotion program
      on improving cardiovascular disease risk factors. METHODS: In St Louis, Missouri
      from 2005 to 2006, 151 employees (134 F, 17 M, 81% overweight/obese) participated
      in a cohort-randomized trial comparing assessments + intervention (worksite A)
      with assessments only (worksite B) for 1 year. All participants received personal
      health reports containing their assessment results. The intervention was designed
      to promote physical activity and favorable dietary patterns using pedometers,
      healthy snack cart, WeightWatchers(R) meetings, group exercise classes, seminars,
      team competitions, and participation rewards. Outcomes included BMI, body
      composition, blood pressure, fitness, lipids, and Framingham 10-year coronary
      heart disease risk. RESULTS: 123 participants, aged 45+/-9 yr, with BMI 32.9+/
      8.8 kg/m(2) completed 1 year. Improvements (P< or =0.05) were observed at both
      worksites for fitness, blood pressure, and total-, HDL-, and LDL-cholesterol.
      Additional improvements occurred at worksite A in BMI, fat mass, Framingham risk
      score, and prevalence of the metabolic syndrome; only the changes in BMI and fat
      mass were different between worksites. CONCLUSION: A multi-faceted worksite
      intervention promoted favorable changes in cardiovascular disease risk factors,
      but many of the improvements were achieved with worksite health assessments and
      personalized health reports in the absence of an intervention.

PMID- 19576929
TI  - Design and evaluation of succinylated soy protein tablets as delayed drug
      delivery systems.
AB  - The impact of succinylation on soy proteins as excipients for delayed delivery of
      drugs in the gastrointestinal tract was studied. Succinylation decreased protein
      solubility and protein charge density at pH 1.2 and increased solubility and zeta
      potential at pH above 4.5. Tablet erosion and swelling were decreased at pH 1.2
      and increased at pH 7.5. FTIR analysis indicated polypeptide chain unfolding as a
      result of succinylation. Tablets of protein succinylated 50% or 100% released
      less than 10% of loaded riboflavin or rifampicin in 2h at gastric pH in the
      presence of pepsin but released these compounds rapidly at intestinal pH.
      Succinylated soy protein tablets were thus gastroresistant, suggesting their use
      as excipients for controlled release of medicinal or nutraceutical agents.

PMID- 19576930
TI  - Alpha-synuclein-glucocerebrosidase interactions in pharmacological Gaucher
      models: a biological link between Gaucher disease and parkinsonism.
AB  - A growing body of experimental and clinical literature indicates an association
      between Gaucher disease and parkinsonism, raising the possibility that convergent
      mechanisms may contribute to neurodegeneration in these disorders. The aim of
      this study was to determine whether there is a relationship between alpha
      synuclein (alpha-syn), a key protein in Parkinson's disease pathogenesis, and
      abnormalities in glucocerebroside (GC) catabolism that lead to the development of
      Gaucher disease. We inhibited glucocerebrosidase (GCase) with conduritol B
      epoxide (CBE) in neuroblastoma cells and mice to test whether a biological link
      exists between GCase activity and alpha-syn. After CBE exposure, enhanced alpha
      syn protein was detected in differentiated cells challenged with CBE as compared
      to vehicle, with no change in alpha-syn mRNA. In the mouse model, after one
      injection of CBE, elevated nigral alpha-syn levels were also detected. Analyses
      by Western blot and confocal microscopy revealed that normal alpha-syn
      distribution was perturbed after CBE exposure with its accumulation apparent
      within nigral cell bodies as well as astroglia. These findings raise the
      possibility that alpha-syn may contribute to the cascade of events that promote
      neuronal dysfunction in Gaucher disease and are the first to implicate this
      protein as a plausible biological intersection between Gaucher disease and
      parkinsonism using a pharmacological model.

PMID- 19576931
TI  - Dynamic Causal Models for phase coupling.
AB  - This paper presents an extension of the Dynamic Causal Modelling (DCM) framework
      to the analysis of phase-coupled data. A weakly coupled oscillator approach is
      used to describe dynamic phase changes in a network of oscillators. The use of
      Bayesian model comparison allows one to infer the mechanisms underlying
      synchronization processes in the brain. For example, whether activity is driven
      by master-slave versus mutual entrainment mechanisms. Results are presented on
      synthetic data from physiological models and on MEG data from a study of visual
      working memory.

PMID- 19576932
TI  - A Bayesian statistical analysis of behavioral facilitation associated with deep
      brain stimulation.
AB  - Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease
      and is being investigated as a treatment for chronic depression, obsessive
      compulsive disorder and for facilitating functional recovery of patients in
      minimally conscious states following brain injury. For all of these applications,
      quantitative assessments of the behavioral effects of DBS are crucial to
      determine whether the therapy is effective and, if so, how stimulation parameters
      can be optimized. Behavioral analyses for DBS are challenging because subject
      performance is typically assessed from only a small set of discrete measurements
      made on a discrete rating scale, the time course of DBS effects is unknown, and
      between-subject differences are often large. We demonstrate how Bayesian state
      space methods can be used to characterize the relationship between DBS and
      behavior comparing our approach with logistic regression in two experiments: the
      effects of DBS on attention of a macaque monkey performing a reaction-time task,
      and the effects of DBS on motor behavior of a human patient in a minimally
      conscious state. The state-space analysis can assess the magnitude of DBS
      behavioral facilitation (positive or negative) at specific time points and has
      important implications for developing principled strategies to optimize DBS
      paradigms.

PMID- 19576933
TI  - Burn injury induces the expression of cystine/glutamate transporter (x(c)(-)) in
      mouse T cells.
AB  - System x(c)(-) transporter, formed by the association of CD98 and xCT proteins,
      regulates the import of cystine into cells and is poorly expressed in T
      lymphocytes. Thermal injury is associated with high oxidative stress, decreased
      levels of glutathione (GSH) and protein deficiency, all described as promoters of
      xCT expression and system x(c)(-) activity. T cell dysfunction is a consequence
      of thermal injury and has been related to oxidative stress. In order to evaluate
      if thermal injury induced system x(c)(-) expression in splenic T lymphocytes,
      cells were isolated from sham- and burn-injured mice at day 10 post-burn and
      cultured in 2-mercaptoethanol (2-ME)-rich and -free media. Isolated splenic T
      cells were stimulated and cell proliferation, system x(c)(-) expression and
      cystine transport activity were measured. Our results demonstrate that only burn
      injured T cells express xCT and proliferate in (2-ME)-free media. In these cells,
      viability and CD25 expression was higher than control T cells. x(c)(-) system
      expression was responsible for significantly higher (14)C-cystine uptake by burn
      injured T cells and its inhibition by sulfasalazine (SASP) decreased
      significantly their proliferation. Overall, these results demonstrate that xCT
      expression is induced by thermal injury in T lymphocytes and that cystine import
      by x(c)(-) leads to T cell dysfunction.

PMID- 19576934
TI  - Enhancing the multiplication of nucleopolyhedrovirus in vitro by manipulation of
      the pH.
AB  - Insect nucleopolyhedroviruses (NPVs) are studied widely as agents for biological
      control, as expression vectors for the production of heterologous proteins, and
      as transduction vectors for gene therapy applications. Most of these applications
      rely on the existence of cell lines that allow in vitro multiplication of the
      virus. The influence of pH in the medium culture on the multiplication of SeMNPV,
      HearSNPV and AcMNPV in different cell culture lines was investigated. The study
      showed a strong influence of the medium pH on the virus multiplication with the
      best results at pH 6.5, about half pH unit above the pH of insect culture media
      used most commonly. Additional experiments using a recombinant AcMNPV, expressing
      the green fluorescent protein, suggested that the enhanced virus multiplication
      at pH 6.5 is due mainly to a facilitated entry of the budded virions into the
      cells.

PMID- 19576935
TI  - Preservation of Giardia cysts in stool samples for subsequent PCR analysis.
AB  - Genotyping of Giardia duodenalis cysts in faecal samples has become a regularly
      employed tool by researchers investigating different aspects of the epidemiology
      and pathology of Giardia infection in human and animal populations. However, such
      investigations are often limited to some extent by lack of PCR amplification from
      a proportion of the samples, and this often seems to be associated with the
      storage medium used for the samples. Various different storage media have been
      used in different studies, but investigation of which storage media are most
      appropriate and which may compromise subsequent PCR investigations has not been
      systematically explored to date. In this study, 4 different, commonly used
      storage media were investigated for their effects over time on subsequent PCR
      amplification of DNA from Giardia cysts in stool samples. Microscopic examination
      of the samples and real-time PCR were used to investigate 7 different samples
      over a period of 3 months. Our findings indicate that storage in ethanol or
      potassium dichromate at 4 degrees C gave the best results and, that if
      immunomagnetic separation was used prior to PCR (as may be appropriate for
      samples with low cyst numbers), then storage in potassium dichromate gave the
      best results.

PMID- 19576936
TI  - Increased apoptosis and reduced replication efficiency of the E3 region-modified
      dl309 adenovirus in cancer cells.
AB  - The Adenovirus (Ad) dl309 mutant, which lacks several E3 region genes, has been
      used as the backbone for a number of replication selective cytopathic Ads
      designed to treat tumours. We report that dl309 has enhanced cytopathogenicity in
      a range of different cell lines when compared with Ad5. The E3 region
      modifications found in dl309 contributed to reduced late gene expression in both
      cocksackie-adenovirus receptor (CAR) positive and negative cells. We show that
      completion of the dl309 viral lifecycle was less efficient and apoptosis was
      triggered in the CAR negative K1 thyroid cancer-derived cell line. There was
      increased E1A expression in dl309-infected K1 cells, compared with Ad5, and
      significantly, whereas E1A in Ad5-infected cells was distributed both in the
      nuclear and cytoplasmic compartments, E1A was predominantly nuclear in dl309
      infected K1 cells. From these results we conclude that the regions of dl309 that
      are deleted or otherwise modified can contribute to viral replication and
      inhibition of apoptosis, possibly indirectly by regulating E1A. These data have
      implications in the development of dl309-based Ads for the treatment of tumours
      in vivo.

PMID- 19576937
TI  - Odor attributes change in relation to the time of the year. Cinnamon odor is more
      familiar and pleasant during Christmas season than summertime.
AB  - Aim of the present study was to examine whether odor attributes like pleasantness
      and familiarity change in relation to the time of the year. In the first part of
      the study a total of 100 subjects answered to questions without odor presentation
      whether a certain odor was more related to summertime or Christmas season.
      Another 41 and 51 subjects rated the familiarity and hedonicity of 12 odors
      either during summertime or Christmas season, respectively. Importantly, this
      investigation was performed at the same place within a science museum during
      stable environmental conditions. Subjects reported that rose odor was more
      related to summertime, whereas orange, cinnamon, and cloves were more associated
      with Christmas season with cinnamon being most intimately connected to this time
      of the year. Moreover, subjects showed significantly higher familiarity and
      pleasantness ratings when they smelled cinnamon during the Christmas season than
      during summertime. Taken together, this study demonstrated that attributes of
      some odors change throughout the year.

PMID- 19576938
TI  - Decreased glutathione levels and antioxidant enzyme activities in untreated and
      treated schizophrenic patients.
AB  - There is substantial evidence found in the literature that supports the fact that
      the presence of oxidative stress may play an important role in the
      physiopathology of schizophrenia. Previous studies have reported the occurrence
      of impairments in the glutathione levels and the activities of the antioxidant
      enzymes in patients suffering from schizophrenia. However, most of these studies
      were performed on treated patients. The present study evaluated treated
      schizophrenic patients (n=52) along with neuroleptic-free or untreated
      schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione
      levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized
      glutathione (GSSG) as well as the activities of the antioxidant enzymes:
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)
      were measured. The psychopathology of the patients was assessed through the
      Clinical Global Impressions-severity (CGI-severity). The tests revealed that in
      comparison with the healthy controls, the schizophrenic patients showed
      significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic
      patients, the activities of the antioxidant enzymes SOD and CAT were recorded to
      be significantly lower in untreated patients than in the treated ones. In
      addition, the levels of both GSHt and GSHr were found to be inversely correlated
      with the obtained CGI-severity score. These results evidently suggest that a
      decrease in the glutathione levels and the activities of the antioxidant enzymes
      in patients diagnosed with schizophrenia is not related to neuroleptic treatment
      and could be considered as a biological indicator of the degree of severity of
      the symptoms of schizophrenia.

PMID- 19576939
TI  - Phloridzin-induced melanogenesis is mediated by the cAMP signaling pathway.
AB  - Melanogenesis is a physiological process that results in the synthesis of melanin
      pigments, which play a crucial protective role in protection against skin
      photocarcinogenesis. Phloridzin is a phloretin 2'-glucoside that is found in many
      parts of the apple tree that reportedly increases tyrosinase activity and melanin
      contents through inhibition of protein kinase C (PKC) activity in B16 melanoma
      cells. In this study, we attempted to accurately determine the effects and
      mechanisms of action of phloridzin on melanogenesis. Specifically, we observed
      that phloridzin-induced a dose-dependent increase in tyrosinase activity and
      melanin contents, and that these changes were accompanied by an increase in the
      levels of tyrosinase and the tyrosinase-related proteins, TRP-1 and TRP-2.
      Furthermore, the cAMP-dependent protein kinase A (PKA) inhibitor H89 impaired the
      response of the tyrosinase activity and melanin synthesis to phloridzin.
      Additionally, phloridzin stimulated cAMP production and phosphorylation of the
      cAMP-response element binding protein (CREB). Taken together, the results of this
      study indicate that phloridzin increases tyrosinase gene expression through the
      cAMP signaling pathway, thereby leading to the stimulation of melanogenesis.

PMID- 19576940
TI  - Molecular adjuvants for malaria DNA vaccines based on the modulation of host-cell
      apoptosis.
AB  - Malaria represents a major global health problem but despite extensive efforts,
      no effective vaccine is available. Various vaccine candidates have been developed
      that provide protection in animal models, such as a gene gun-delivered DNA
      vaccine encoding the circumsporozoite protein (CSP) of Plasmodium berghei. A
      common shortcoming of most malaria vaccines is the requirement for multiple
      immunizations leaving room for improvement even for established vaccine
      candidates such as the CSP-DNA vaccine. In this study, we explored whether
      regulating apoptosis in DNA vaccine transfected host cells could accelerate the
      onset of protective immunity and provide significant protection after a single
      immunization. A pro-apoptotic gene (Bax) was used as a molecular adjuvant in an
      attempt to mimic the immunostimulatory apoptosis triggered by viral or virus
      derived vaccines, while anti-apoptotic genes such as Bcl-XL may increase the life
      span of transfected cells thus prolonging antigen production. Surprisingly, co
      delivery of either Bax or Bcl-XL greatly reduced CSP-DNA vaccine efficacy after a
      single immunization. Co-delivery of Bax for three immunizations still had a
      detrimental effect on protective immunity, while repeated co-delivery of Bcl-XL
      had no negative impact. The fine characterization of humoral and cellular immune
      response modulated by these two molecular adjuvants revealed a previously unknown
      effect, i.e., a shift in the Th-profile. These results demonstrate that pro- or
      anti-apoptotic molecules should not be used as molecular adjuvants without
      careful evaluation of the resulting immune response. This finding represents yet
      another example that strategies to enhance vaccine efficacy developed for other
      model systems such as viral diseases cannot easily be applied to any vaccine.

PMID- 19576941
TI  - A relapse of systemic type juvenile idiopathic arthritis after a rubella
      vaccination in a patient during a long-term remission period.
AB  - An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis
      (JIA) had maintained in remission for the previous 4 years while taking only a
      small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart
      failure five days after receiving a live-attenuated rubella vaccine, which was a
      primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies
      increased, and her laboratory findings such as a leukocytosis, elevated serum
      levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the
      findings observed during her previous JIA active stage. After being
      administration of co-therapy with steroid pulse, ibuprofen, methotrexate and
      phosphodiesterase inhibitor gradually improved her clinical symptoms such as
      spiky fever, heart failure and arthralgia. Her intermittent fever and increased
      serum levels of CRP and IL-6, however, have been sustained for more than 2 years,
      and this prolonged active clinical course therefore differed from her previous
      JIA active stage.This abrupt relapse only five days after vaccination was
      suggested not to be directly related with rubella infection, but instead to be
      related with the molecular mimicry between rubella and JIA.

PMID- 19576942
TI  - Effective CD8(+) T cell priming and tumor protection by enterotoxin B subunit
      conjugated peptides targeted to dendritic cells.
AB  - In our previous studies we have shown that bacterial enterotoxin B subunits are
      effective vehicles to deliver antigen into the MHC class I processing route. Here
      we have used the non-toxic Escherichia coli heat labile enterotoxin B subunit
      (EtxB) conjugated to OVA peptide (EtxB-peptide) to address the impact on
      induction of specific CD8(+) T cells in vivo. Although incubation of DCs with
      these EtxB-peptide conjugates as such did not induce DC maturation in vitro MHC
      class I antigen presentation was much more efficient as compared to peptide
      alone. Antigen presentation was further enhanced upon DC maturation with the TLR
      4 ligand LPS. Injection of matured DCs incubated with EtxB-peptide conjugates
      lead to strong induction of OVA-specific CD8(+) T lymphocytes and fully prevented
      the outgrowth of lethal B16 melanoma in wild type mice. Our data demonstrate that
      bacterial non-toxic B subunit-peptide conjugates are potent vaccine vehicles for
      induction of protective CD8(+) T cell responses.

PMID- 19576943
TI  - Evaluating the potential public health impact of a Staphylococcus aureus vaccine
      through use of population-based surveillance for invasive methicillin-resistant
      S. aureus disease in the United States.
AB  - We evaluated the potential effects of a hypothetical vaccine in preventing
      invasive methicillin-resistant Staphylococcus aureus (MRSA) disease in the United
      States. Using an active, population-based surveillance program, we estimated
      baseline disease rates in the United States and compared three distinct
      vaccination strategies which targeted adults > or =65 years of age, persons at
      risk for recurrent invasive infection, and patients at hospital discharge. The
      strategies were projected to reduce the burden of invasive MRSA disease by 12.1%,
      13.9% and 17.6%, respectively; with the strategy of vaccinating both adults > or
      =65 years of age and all adults at hospital discharge having the greatest impact
      per dose. Our data suggest that availability of an effective S. aureus vaccine
      could result in substantial reductions in invasive MRSA disease incidence. As
      candidate vaccines are evaluated, these data will be important in determining the
      optimal vaccination strategy.

PMID- 19576944
TI  - Safety and immunogenicity of sequential pneumococcal immunization in preschool
      asthmatics.
AB  - OBJECTIVE: Respiratory infections are major triggers of exacerbations in
      preschool asthma. Many countries' guidelines recommend immunization against
      pneumococci for patients suffering from chronic airway disease. Beyond infancy,
      however, data on the immunogenicity and safety are scarce. Also, the interval
      between priming and booster is a matter of debate. PATIENTS AND METHODS: Seventy
      preschool asthmatics (2-5-year-old; mild to moderate asthma) underwent sequential
      immunization: one dose of seven-valent pneumococcal conjugate vaccine (PCV-7)
      followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV
      23). We randomly assigned half of the vaccinees to receive PPV-23 eight weeks
      after PCV-7 (group A), and the rest to a 10-month interval (group B).
      Pneumococcal antibody concentrations to serotype 4, 5, 6B, 7, 9V, 14, 18c, 19F
      and 23F were determined initially, after two and 12 months after PCV-7. Local and
      systemic reactions to each vaccine were recorded. RESULTS: Initially, depending
      on the serotype, up to 79.4% (group A) or 80.4% (group B) individuals did not
      reach the protective antibody threshold of 0.35 microg/ml. Sequential
      pneumococcal immunization was immunogenic in preschool asthmatics, inducing
      protection in the majority of our children. Subjects boostered after eight weeks
      had significantly lower antibody levels than those boostered after 10 months.
      Local and systemic adverse events were mild in character and self-limiting.
      CONCLUSIONS: Although both sequential pneumococcal vaccine regimens were safe and
      immunogenic among preschool asthmatics, immunogenicity was higher when the
      booster was given after 10 months.

PMID- 19576945
TI  - The Australian Childhood Immunisation Register-A model for universal immunisation
      registers?
AB  - The Australian Childhood Immunisation Register (ACIR) was established in 1996 as
      an opt-out register built on the platform of Medicare, the universal national
      health insurance scheme. Introduction of financial incentives for providers and
      parents, linked to the ACIR, followed from 1998. Over the subsequent decade,
      national levels for receipt of all vaccines by 12, 24 and 72 months of age have
      risen to 91%, 93%, and 88%, respectively. Conscientious objection to immunisation
      can be registered, with retention of eligibility for incentives. The ACIR has
      been important in implementation of a range of measures to improve childhood
      immunisation coverage in Australia. Linkage of a universal childhood immunisation
      register to national health insurance schemes has potential applicability in a
      variety of settings internationally.

PMID- 19576946
TI  - Dietary catechol causes increased oxidative DNA damage in the livers of mice
      treated with acetaminophen.
AB  - We have shown that direct reaction of catechol with nitric oxide (NO) results in
      generation of reactive oxygen and nitrogen species (RNS) through semiquinone
      radical formation, leading to oxidative DNA damage in rat forestomach. In the
      present study, we investigated whether dietary catechol systemically exerts the
      same effects under NO-rich circumstances, when given before and during induction
      of inflammatory lesions. Male ICR mice were treated with or without 0.8% catechol
      in the diet for 2 weeks followed by acetaminophen (APAP) administration at a dose
      of 300mg/kg by single i.p. injection. Along with several indicators of APAP
      induced hepatitis, 8-hydroxydeoxyguanosine (8-OHdG) levels and
      immunohistochemistry for 3-nitrotyrosine (NO(2)Tyr) in the livers were examined
      at 1.5, 4 and 24h after APAP injection. 8-OHdG was significantly increased at 24h
      in the co-treatment group, but not with either catechol or APAP alone. Elevation
      of serum ALT and AST activities, decrease of reduced glutathione levels and
      histopathological liver changes were observed to the same extents in both APAP
      treated groups. In view of the finding of positive hepatocytes for NO(2)Tyr prior
      to generation of 8-OHdG, the process of oxidative DNA damage might involve RNS
      formation. Precise quantitative analysis of NO(2)Tyr by means of liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) in an additional study
      with the same experimental protocol confirmed increase of RNS due to the reaction
      of catechol with NO produced after APAP-induced hepatitis. The overall data imply
      that antioxidants with a catechol structure can cause oxidative DNA damage under
      inflammatory conditions.

PMID- 19576947
TI  - Spatiotemporal cortical activation underlying dilemma decision-making: an event
      related potential study.
AB  - Event-related brain potentials (ERPs) were measured when 18 Chinese subjects
      performed a dilemma decision task. During this task, subjects were required to
      decide who to rescue when two relatives (FN-FN, e.g., father and mother) or two
      strangers (SN-SN: stranger A and stranger B) were buried in the debris after a
      great earthquake. All subjects had experienced the great Sichuan earthquake on
      May 12th, 2008 in Chengdu city, China. Scalp ERP analysis revealed that FN-FN
      elicited a much more positive deflection (P2) than did SN-SN, which might reflect
      stimulus evaluation and conflict detection in the initiation of decision-making.
      In addition, a greater positivity (P350-450) in FN-FN as compared to SN-SN was
      found between 350 and 450ms post-stimulus, after hearing aftershock information.
      Dipole source analysis of difference wave (FN-FN minus SN-SN) indicated that two
      generators of the P350-450, localized in the parahippocampal gyrus and the
      cuneus, might be involved in dilemma interference resolution processes.

PMID- 19576948
TI  - P3 event-related potential impairments in antisocial and psychopathic
      individuals: a meta-analysis.
AB  - Prior findings on P3 event-related potential deficits in antisocial populations
      are mixed and it has been suggested that these abnormalities may not apply to
      psychopaths. A meta-analysis of 38 studies (total N=2616) was conducted to
      investigate the relationship of P3 measures to antisocial behavior. Reduced P3
      amplitudes (d=0.252, p<.001) and longer P3 latencies (d=0.130, p=.019) were
      significantly associated with antisocial behavior across all electrode sites, and
      when using both normal and non-normal control groups. A significant moderating
      effect of electrode site indicated longer latencies at Fz but not Pz. Compared to
      non-psychopathic offenders, psychopathic offenders showed P3 amplitudes
      impairments in standard oddball tasks, but not other tasks. Findings suggest that
      reduced P3 amplitudes and prolonged P3 latencies may reflect inefficient
      deployment of neural resources in processing cognitive task-relevant information
      in individuals characterized with generic antisocial behavior (i.e., aggression,
      antisocial personality disorder, conduct disorder/oppositional-defiant disorder,
      and psychopathy), whereas this association in psychopaths may be moderated by the
      type of tasks.

PMID- 19576949
TI  - Transcriptional activation of the gamma-globin gene in baboons treated with
      decitabine and in cultured erythroid progenitor cells involves different
      mechanisms.
AB  - OBJECTIVE: To investigate the mechanism(s) responsible for increased gamma-globin
      expression in vivo in decitabine-treated baboons and in vitro in cultured
      erythroid progenitor cells (EPC) from adult baboon bone marrow (BM). MATERIALS
      AND METHODS: Fetal liver, adult BM erythroid cells pre- and post-decitabine, and
      cultured EPCs were analyzed for distribution of RNA polymerase II, histone
      acetylation, and histone H3 (lys4) trimethyl throughout the gamma-globin gene
      complex by chromatin immunoprecipitation. DNA methylation of the gamma-globin
      promoter was determined by bisulfite sequencing. Expression of the baboon Igamma-
      and Vgamma-globin chains was determined by high performance liquid chromatography
      (HPLC). Expression of BCL11A, a recently identified repressor of gamma-globin
      expression, was analyzed by Western blot. RESULTS: Increased gamma-globin
      expression in decitabine-treated baboons and cultured EPC correlated with
      increased levels of RNA polymerase II, histone acetylation, and histone H3 (lys4)
      trimethyl associated with the gamma-globin gene consistent with a transcriptional
      activation mechanism. Cultured EPC expressed the Igamma- and Vgamma-globin chains
      in a pattern characteristic of fetal development. The level of DNA methylation of
      the gamma-globin gene promoter in EPC cultures was similar to BM erythroid cells
      from normal adult baboons. Different BCL11A isoforms were observed in BM
      erythroid cells and cultured EPC. CONCLUSION: The mechanism responsible for
      increased gamma-globin expression in cultured EPC was unexpectedly not associated
      with increased DNA hypomethylation of the gamma-globin gene promoter compared to
      normal BM erythroid cells, in contrast to BM erythroid cells of decitabine
      treated baboons. Rather, increased fetal hemoglobin in EPC cultures was
      associated with a fetal Igamma/Vgamma chain ratio and a difference in the size of
      the BCL11A protein compared to normal BM erythroid cells.

PMID- 19576950
TI  - Stimulated stromal cells induce gamma-globin gene expression in erythroid cells
      via nitric oxide production.
AB  - OBJECTIVE: We have previously shown that nitric oxide (NO) is involved in the
      hydroxyurea-induced increase of gamma-globin gene expression in cultured human
      erythroid progenitor cells and that hydroxyurea increases NO production in
      endothelial cells via endothelial NO synthase (NOS). We have now expanded those
      studies to demonstrate that stimulation of gamma-globin gene expression is also
      mediated by NOS induction in stromal cells within the bone marrow
      microenvironment. MATERIALS AND METHODS: Using NO analyzer, we measured NO
      production in endothelial and macrophage cell cultures. In coculture studies of
      erythroid and stromal cells, we measured globin gene expression during
      stimulation by NO inducers. RESULTS: Hydroxyurea (30-100 microM) induced NOS
      dependent production of NO in human macrophages (up to 1.2 microM). Coculture
      studies of human macrophages with erythroid progenitor cells also resulted in
      induction of gamma-globin mRNA expression (up to threefold) in the presence of
      hydroxyurea. NOS-dependent stimulation of NO by lipopolysaccharide (up to 0.6
      microM) has been observed in human macrophages. We found that lipopolysaccharide
      and interferon-gamma together increased gamma-globin gene expression (up to
      twofold) in human macrophage/erythroid cell cocultures. Coculture of human bone
      marrow endothelial cells with erythroid progenitor cells also induced gamma
      globin mRNA expression (2.4-fold) in the presence of hydroxyurea (40 microM).
      CONCLUSION: These results demonstrate an arrangement by which NO and fetal
      hemoglobin inducers may stimulate globin genes in erythroid cells via the common
      paracrine effect of bone marrow stromal cells.

PMID- 19576952
TI  - Evidence for opioid-induced release of glutamate in guinea pig longitudinal
      muscle-myenteric plexus strip.
AB  - By the use of longitudinal muscle-myenteric plexus (LMMP) strips of the guinea
      pig ileum it should be investigated whether opioids can contribute to an
      excitatory component of the intestinal smooth muscle contractions. LMMP
      preparations were set up in Tyrode solution with 1 micromol/l naloxone present or
      without naloxone from the beginning of tissue preparation. After a 30-min
      equilibration period the twitch contractions evoked by the first and the fifth
      electrical 3-s-stimulus in an 80-s-sequence were significantly higher in the
      tissues prepared and tested without naloxone present. When after continuous
      electrical twitch responses (+) MK-801, an NMDA receptor antagonist (10-100
      micromol/l) was added to the Tyrode solution, the electrically evoked
      contractions were reduced. The inhibition of the twitch response by (+) MK-801
      was less pronounced in the preparations treated continuously with naloxone as
      compared to the otherwise untreated LMMP preparations. Morphine, (1 and 5
      micromol/l), evoked a release of glutamate from this nerve-muscle-preparation. In
      conclusion these experiments provide evidence that endogenously released opioids
      or exogenously applied morphine can release glutamate as an excitatory component
      within the LMMP preparation.

PMID- 19576953
TI  - DNA methyltransferase 3B gene increases risk of early onset schizophrenia.
AB  - OBJECTIVE: Consistent evidence indicated that aberrant DNA methylation may be
      involved in the development of schizophrenia. DNA methyltransferase 3B (DNMT3B)
      is the key methyltransferase in DNA methylation regulations. In this study, we
      investigated the association between DNMT3B polymorphisms and the susceptibility
      of early onset schizophrenia in Chinese Han population. METHODS: Case-control
      (patients=381 and controls=472) and family based (trios=103) study was performed
      through genotyping two tag single nucleotide polymorphisms (rs2424908 and
      rs6119954) covering the whole DNMT3B gene. Single nucleotide polymorphism
      association and haplotype analysis were performed. RESULTS: The frequency of G
      allele of rs6119954 was significantly higher in patients than that in controls
      (P=0.017). Genotype distribution of rs6119954 was significantly different between
      patients and controls (P=0.046). A haplotype-wise analysis revealed a higher
      frequency of the T-G (rs2424908-rs6119954) haplotype in patients than that in
      controls (P=0.033). In the transmission disequilibrium test analysis, G allele of
      rs6119954 was preferentially transmitted in the trios (P=0.030). CONCLUSION: Our
      findings indicate that DNMT3B may be a candidate gene for susceptibility to early
      onset schizophrenia.

PMID- 19576951
TI  - Hematopoietic stem cell origin of adipocytes.
AB  - OBJECTIVE: It has generally been believed that adipocytes are derived from
      mesenchymal stem cells via fibroblasts. We recently reported that
      fibroblasts/myofibroblasts in a number of tissues and organs are derived from
      hematopoietic stem cells (HSCs). In the present study, we tested the hypothesis
      that HSCs also give rise to adipocytes. MATERIALS AND METHODS: Using
      transplantation of a single enhanced green fluorescent protein-positive (EGFP(+))
      HSC and primary culture, we examined generation of adipocytes from HSCs. RESULTS:
      Adipose tissues from clonally engrafted mice showed EGFP(+) adipocytes that
      stained positive for leptin, perilipin, and fatty acid binding protein 4. A diet
      containing rosiglitazone, a peroxisome proliferator-activated receptor-gamma
      agonist, significantly enhanced the number of EGFP(+) adipocytes. When EGFP(+)
      bone marrow cells from clonally engrafted mice were cultured under adipogenic
      conditions, all of the cultured cells stained positive with Oil Red O and Sudan
      Black B and exhibited the presence of abundant mRNA for adipocyte markers.
      Finally, clonal culture- and sorting-based studies of Mac-1 expression of
      hematopoietic progenitors suggested that adipocytes are derived from HSCs via
      progenitors for monocytes/macrophages. CONCLUSION: Together, these studies
      clarify the current controversy regarding the ability of HSCs to give rise to
      adipocytes. Furthermore, our primary culture method that generates adipocytes
      from uncommitted hematopoietic cells should contribute to the studies of the
      mechanisms of early adipocytic differentiation and may lead to development of
      therapeutic solutions for many general obesity issues.

PMID- 19576954
TI  - Cognitive demands impair postural control in developmental dyslexia: a negative
      effect that can be compensated.
AB  - Children with developmental dyslexia exhibit delayed reading abilities and
      various sensori-motor deficits. The way these various symptoms interact remain
      poorly understood. The objective of this study was twofold. First, we aimed to
      investigate whether postural control was impaired in dyslexic children when
      cognitive demands are increased. Second, we checked whether this effect could be
      reduced significantly by a treatment aiming to recalibrate ocular proprioception.
      Twelve dyslexic and fifteen treated dyslexic children (>3 months of treatment)
      were compared with twelve non-dyslexic children in two conditions (mean age:
      11.6+/-2.1, 12.5+/-1.5 and 10.6+/-1.7 years respectively). In a first condition
      they maintained balance while fixating a point in front of them. In the second
      condition the postural task was combined with a silently reading one. Balance was
      assessed by means of a force plate. Results demonstrated that the mean velocity
      (i.e. the total length) of the center of pressure (CoP) displacement was
      increased in the reading task only for the dyslexic group. Interestingly, for the
      treated children, an inverse tendency was observed: the mean velocity (i.e. the
      total length) and the surface of the 90% confidence ellipse of the CoP
      displacement decreased for 13/15 patients and for 12/15 patients respectively,
      while performing the reading task. Values remained similar to those observed for
      the control children. Altogether, these results strongly suggest that cognitive
      demands can impair postural control in developmental dyslexia but this
      interaction could be normalized. These results sustain the hypothesis of a
      cerebellar origin for dyslexia.

PMID- 19576955
TI  - High recurrence of the R1006C NOTCH3 mutation in central Italian patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL).
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a heritable small-vessel disease caused by
      mutations in NOTCH3 gene and clinically characterized by recurrent ischemic
      strokes, migraine with aura, psychiatric symptoms, cognitive decline and
      dementia. Direct sequencing of NOTCH3 gene in 90 Italian patients of sixty-three
      unrelated families identified four heterozygous mutations (R141C and C144F in
      exon 4, G528C in exon 10 and R1006C in exon 19) in fifteen probands and sixteen
      relatives. We detected seventeen heterozygous/homozygous polymorphisms, four of
      them novel. Here we report the high recurrence of R1006C mutation in ten families
      all originate from a restricted area of central Italy, the town of Ascoli Piceno
      and same neighbour villages. We also developed a PCR-Restriction Fragment Length
      Polymorphism (RFLP) assay to analyze the R1006C mutation. Our findings might
      suggest, for this mutation, the presence of a common ancestor.

PMID- 19576956
TI  - Unmyelinated afferents in human skin and their responsiveness to low temperature.
AB  - In humans, there are different types of cutaneous cold-sensitive afferents
      responsible for cold sensation and cold pain. Innocuous cold is primarily
      mediated by a population of slow A delta afferents, based on psychophysical and
      neurophysiological studies. Noxious cold (usually below 15 degrees C) is
      mediated, at least in part, by polymodal nociceptors. There is also a population
      of unmyelinated afferents responsive to innocuous low temperature, some of which
      also respond to heat, whose sensory function has not been completely defined. A
      paradoxical hot/burning evoked by cooling is unmasked by A-fibre block, and
      similar sensations are evoked by applying simultaneous cool and warm stimuli to
      adjacent skin areas. These unmyelinated fibres activated by innocuous cooling
      (and heating) may contribute to this hot/burning sensation, along with other
      thermoregulatory functions.

PMID- 19576957
TI  - Negative BOLD effect on somato-motor inhibitory processing: an fMRI study.
AB  - Inhibiting inappropriate behavior and thoughts in the current context is an
      essential ability for humans, but the neural mechanisms for response inhibitory
      processing are a matter of continuous debate. The aim of this event-related
      functional magnetic resonance imaging (fMRI) study was to evaluate the negative
      blood oxygen level dependent (BOLD) effect on inhibitory processing during go/no
      go paradigms. Fifteen subjects performed two different types of somatosensory
      go/no-go paradigm: (1) button press and (2) count. Go and no-go stimuli were
      presented with an even probability. We observed a common negative activation
      during Movement No-go and Count No-go trials in the right SFG, corresponding to
      BA 8. These findings suggest that the right SFG region was responsible for the
      negative BOLD effect on inhibitory processing, which was independent of the
      required response mode. We hypothesized several possible explanations for the
      deactivation of the SFG during no-go trials.

PMID- 19576958
TI  - Replication of an association of a promoter polymorphism of the dopamine
      transporter gene and Attention Deficit Hyperactivity Disorder.
AB  - Genetic associations for Attention Deficit Hyperactivity Disorder (ADHD), a
      common highly heritable childhood behavioural disorder, require replication in
      order to establish whether they are true positive findings. The current study
      aims to replicate recent association findings from the International Multi-centre
      ADHD Genetics (IMAGE) project in one of the most studied genes related to ADHD,
      the dopamine transporter (DAT1) gene. In a family-based sample of 450 ADHD
      probands, three Single Nucleotide Polymorphism (SNP) markers have been genotyped
      using TaqMan assays. Transmission Disequilibrium Test analysis demonstrates that
      one of three SNP markers (rs11564750) in the 5' promoter region of the gene is
      significantly associated with ADHD (P=0.02). This provides further evidence that
      in addition to the well-known and investigated 3'UTR polymorphism associated with
      ADHD, there is potentially a further association signal emanating from the 5'
      promoter region of the gene. Further replication and functional studies are now
      required to fully understand the consequence of polymorphisms present at both the
      5' and 3' ends of the DAT1 gene and their role in ADHD pathophysiology.

PMID- 19576959
TI  - Microneurography of pruritus.
AB  - Microneurography of human skin nerves has recently contributed detailed
      information on the peripheral input leading to itch sensations. In this context
      it has been demonstrated that itch induced by different agents activates
      different neuronal populations in the PNS. Histamine acts on a specific subgroup
      of mechano-insensitive C-fibers which are also sensitive to other endogenous
      mediators, e.g. prostaglandine E2 and acetylcholine, and to capsaicin. Since
      these agents can also provoke pain, a "selectivity hypothesis" may explain the
      differentiation between the itch and pain pathways. Though histamine seemed to be
      the prototypical itch mediator it plays a minor role in part of the clinical itch
      states. Experimentally, the spicules of mucuna pruriens (cowhage) induce strong
      non-histaminergic itch. It turned out that they excite an entirely different
      population of C-fibers, namely mechano-responsive polymodal nociceptor units
      (CMH) and Adelta units. The neuronal mechanisms of clinically important pruritic
      states, e.g. in uremia are still unexplored.

PMID- 19576960
TI  - Prolonged exposure to ammonia increases extracellular glutamate in cultured rat
      astrocytes.
AB  - Abnormal alteration of brain function is a characteristic complication of hepatic
      encephalopathy in both acute and chronic liver failure. Previous studies suggest
      that the pathogenesis of hepatic encephalopathy involves chronic glial edema with
      subsequent alteration of glioneuronal communication, N-methyl-d-aspartate (NMDA)
      receptor activation, and oxidative/nitrosative stress. In the present study, we
      investigated extracellular glutamate levels in cultured astrocytes under
      prolonged exposure to ammonia. Using an enzyme-linked high-performance liquid
      chromatography assay to detect glutamate, prolonged (48 h) exposure of cultured
      astrocytes to ammonia resulted in a concentration- and time-dependent increase in
      extracellular glutamate. Similar increases were observed when ammonia-containing
      medium (pH 7.8) was adjusted to the pH of control medium (pH 7.4), indicating
      that the effect is not due to pH. Treatment of astrocytes with an antioxidant (l
      ascorbic acid), an NADPH oxidase inhibitor (apocynin), a Ca2+ chelator (BAPTA
      AM), an NMDA receptor antagonist (NK801), or a mitochondrial permeability
      transition inhibitor (cyclosporine A) suppressed the increase of extracellular
      glutamate in response to prolonged ammonia exposure. Prolonged exposure to
      ammonia increased extracellular glutamate through the NMDA receptor, increased
      intracellular Ca2+ levels, and upregulation of excitatory amino acids. The
      addition of ATP further increased extracellular glutamate levels in astrocytes
      subjected to prolonged ammonia treatment (5mM, 48 h) in a dose-dependent manner.
      These results indicate that the deregulation of glutamate release from astrocytes
      may contribute to the dysfunction of glutamatergic neurons in patients with acute
      liver failure (ALF).

PMID- 19576961
TI  - Characteristics of the control of standing posture during pregnancy.
AB  - During pregnancy, the physical and mental states greatly change. We investigated
      the influences of pregnancy and anxiety on postural control in pregnant women (P)
      standing upright in the late trimester. An analysis of posturograms revealed that
      the area of body sway and length of antero-posterior body sway were greater in P
      than those in non-pregnant controls (NP). No difference was found in the medio
      lateral body sway between P and NP. Fast Fourier transform analysis of body sway
      showed that the percentile power of the 1.0-10.0Hz band in the medio-lateral axis
      was smaller in P than in NP irrespective of whether the eyes were open or closed.
      P were divided into a high (HA) and low (LA) anxiety group on the basis of state
      anxiety scored by Spielberger's State- and Trait-Anxiety Inventory. A positive
      correlation was identified between state anxiety and the area of body sway in HA
      standing with eyes open. This correlation was diminished when the eyes were
      closed. Body sway of over 1Hz is generally stabilized by somatosensory input,
      therefore, the results show that body sway in the medio-lateral axis is
      stabilized in P by increasing the sensitivity to somatosensory cues. High anxiety
      during pregnancy destabilizes the standing posture when the eyes are open. The
      correlation between anxiety and body sway revealed by our previous studies in
      college students was also confirmed in P, suggesting that humans with high
      anxiety abstract visual cues differently from those with low anxiety.

PMID- 19576963
TI  - When the brain goes diving: glial oxidative metabolism may confer hypoxia
      tolerance to the seal brain.
AB  - Deep diving mammals have developed strategies to cope with limited oxygen
      availability when submerged. These adaptations are associated with an increased
      neuronal hypoxia tolerance. Brain neurons of the hooded seal Cystophora cristata
      remain much longer active in hypoxic conditions than those of mice. To understand
      the cellular basis of neuronal hypoxia tolerance, we studied neuroglobin and
      cytochrome c in C. cristata brain. Neuroglobin, a respiratory protein typically
      found in vertebrate neurons, displays three unique amino acid substitutions in
      hooded seal. However, these substitutions unlikely contribute to a modulation of
      O(2) affinity. Moreover, there is no significant difference in total neuroglobin
      protein levels in mouse, rat and seal brains. However, in terrestrial mammals
      neuroglobin resided exclusively in neurons, whereas in seals neuroglobin is
      mainly located in astrocytes. This unusual localization of neuroglobin is
      accompanied by a shift in the distribution of cytochrome c. In seals, this marker
      for oxidative metabolism is mainly localized in astrocytes, whereas in
      terrestrial mammals it is essentially found in neurons. Our results indicate that
      in seals aerobic ATP production depends significantly on astrocytes, while
      neurons rely less on aerobic energy metabolism. This adaptation may imbue seal
      neurons with an increased tolerance to hypoxia and potentially also to reactive
      oxygen species, and may explain in part the ability of deep diving mammals to
      sustain neuronal activity during prolonged dives.

PMID- 19576962
TI  - Transcutaneous electrical nerve stimulation at both high and low frequencies
      activates ventrolateral periaqueductal grey to decrease mechanical hyperalgesia
      in arthritic rats.
AB  - Transcutaneous electric nerve stimulation (TENS) is widely used for the treatment
      of pain. TENS produces an opioid-mediated antinociception that utilizes the
      rostroventromedial medulla (RVM). Similarly, antinociception evoked from the
      periaqueductal grey (PAG) is opioid-mediated and includes a relay in the RVM.
      Therefore, we investigated whether the ventrolateral or dorsolateral PAG mediates
      antinociception produced by TENS in rats. Paw and knee joint mechanical
      withdrawal thresholds were assessed before and after knee joint inflammation (3%
      kaolin/carrageenan), and after TENS stimulation (active or sham). Cobalt chloride
      (CoCl(2); 5 mM) or vehicle was microinjected into the ventrolateral
      periaqueductal grey (vlPAG) or dorsolateral periaqueductal grey (dlPAG) prior to
      treatment with TENS. Either high (100 Hz) or low (4 Hz) frequency TENS was then
      applied to the inflamed knee for 20 min. Active TENS significantly increased
      withdrawal thresholds of the paw and knee joint in the group microinjected with
      vehicle when compared to thresholds prior to TENS (P<0.001) or to sham TENS
      (P<0.001). The increases in withdrawal thresholds normally observed after TENS
      were prevented by microinjection of CoCl(2) into the vlPAG, but not the dlPAG
      prior to TENS and were significantly lower than controls treated with TENS
      (P<0.001). In a separate group of animals, microinjection of CoCl(2) into the
      vlPAG temporarily reversed the decreased mechanical withdrawal threshold
      suggesting a role for the vlPAG in the facilitation of joint pain. No significant
      difference was observed for dlPAG. We hypothesize that the effects of TENS are
      mediated through the vlPAG that sends projections through the RVM to the spinal
      cord to produce an opioid-mediated analgesia.

PMID- 19576964
TI  - Differential role of gonadal hormones on kainic acid-induced neurodegeneration in
      medial amygdaloid nucleus of female and male rats.
AB  - Sex hormones contribute to modulating brain functions throughout the life span.
      It has been suggested that estrogen prevents neuronal loss in different areas of
      the CNS such as the hippocampus. However there are less consistent data on its
      effects on the amygdala. Kainic acid (KA) is used to produce seizures that mimic
      those of temporal lobe epilepsy in humans. At high doses in animal models, KA
      induces neurotoxicity, particularly in the medial amygdaloid nuclei (MeA). It is
      uncertain whether the gonadal hormones are protective or not against this
      neurotoxicity in the MeA. Here we show that a single dose of KA induces
      neurodegeneration in the subnuclei of the MeA of rats with different degrees of
      intensity in males and females. A differential neuroprotective effect of the
      gonadal hormones was also observed. In diestrous rats, massive neuronal death
      similar to that in the ovariectomized females was detected. MeA neurons of
      proestrous rats, like the ovariectomized treated with estrogen, were
      significantly less affected by the KA. Testosterone produced a mild
      neuroprotective action, but dihydrotestosterone did not protect. A similar
      pattern was observed in all male groups. Together, the results indicate that
      estrogen protects MeA neurons from KA neurotoxicity. Androgens are only partially
      neuroprotective, with this effect being found only in testosterone, probably
      through its conversion to estrogen by aromatase.

PMID- 19576967
TI  - Acceleration of pentylenetetrazol seizure kindling associated with induction of
      sensitized visual responses evoked by strobe stimulation.
AB  - Exposure of normal adult rats of a variety of species to trains of light flashes
      leads to acquisition of an enduring high amplitude visual cortical response
      [Uhlrich DJ, Manning KA, O'Laughlin ML, Lytton WW (2005) Photic-induced
      sensitization: acquisition of an augmenting spike-wave response in the adult rat
      through repeated strobe exposure. J Neurophysiol 94:3925-3937]. The photically
      induced sensitized response exhibits epileptiform characteristics, including
      spike-wave morphology, tendency to generalize across the brain, and sensitivity
      to the anti-epileptic drug ethosuximide. These findings and anecdotal clinical
      reports raise the possibility that certain sensory stimulation could induce
      neural plastic changes that affect seizures in some individuals. We hypothesize
      that photic-induced sensitization can prime seizure-related neural circuitry,
      resulting in exacerbation of seizures. To test this we compared seizure kindling
      rates using the pentylenetetrazol (PTZ) model of epileptogenesis in sensitized
      and unsensitized adult Sprague-Dawley rats. Experimental group rats were
      sensitized by exposure to repetitive stroboscopic stimulation over 4-6 days until
      the sensitized photic response fully developed and response magnitude stabilized
      at its highest plateau. Rats then received a sub-convulsive injection of PTZ (24
      mg/kg i.p.) every other day until they attained class 5 seizures. Control rats
      were not strobed or sensitized, but were otherwise treated identically. Chronic
      electrodes overlying the dura in occipital cortex recorded the primary visual
      response. Similar electrodes near the border of somatosensory and motor cortex
      (SM) were used to record spread of the sensitized response to a patently non
      visual region. Rat behavior was monitored by direct observation and digital
      audio/video recording. All control rats and seven of 14 photically sensitized
      rats kindled seizures at rates consistent with those reported previously.
      However, the seven other photically sensitized rats displayed markedly
      accelerated seizure kindling. Rats with accelerated kindling showed greater
      spread of the sensitized visual response to somato-motor cortex and, when tested
      in a post hoc experiment, exhibited a higher likelihood of photo-triggered
      seizures. These results indicate that photic-induced sensitization in susceptible
      individuals can prime neural circuitry involved in the generation of PTZ-kindled
      seizures.

PMID- 19576968
TI  - The essential oils of Chamaecyparis obtusa promote hair growth through the
      induction of vascular endothelial growth factor gene.
AB  - Chamaecyparis obtusa (C. obtusa) is a conifer in the cypress family Cupressaceae,
      native to northeast Asia. The essential oils of C. obtusa have antibacterial and
      antifungal effects and several products such as hygienic bands, aromatics, and
      shampoos contain these oils as a natural source of antimicrobial/antifungal
      agents. Interestingly, some consumers suffering from baldness and/or other forms
      of hair loss have reported a hair growth promoting effect of shampoos containing
      these oils. In the present study, the hair growth promoting effect of C. obtusa
      oils was elucidated in an animal model. C. obtusa oils promoted the early phase
      of hair growth in shaved mice. In addition, we examined the molecular effect of
      C. obtusa oils on the regulation of hair morphogenesis and hair growth using the
      human keratinocyte cell line HaCaT. In the current study of hair growth
      regulating genes, the expressions of vascular endothelial growth factor (VEGF),
      transforming growth factor (TGF beta 1), and keratinocyte growth factor(KGF) have
      been analyzed by real-time PCR in HaCaT cells. The essential oils of C. obtusa
      were divided into seven fractions for treatment of HaCaT cells. VEGF transcripts
      were induced by fractions 6 and 7; however, TGF beta 1 and KGF mRNA levels were
      unchanged by C. obtusa oils or fractions. Fraction 7 was separated into seven sub
      fractions and studied further. Sub-fractions E and D significantly increased VEGF
      and KGF gene expression without up-regulating the hair growth inhibition factor,
      TGF beta 1. The components of the two sub-fractions were further analyzed by gas
      chromatography and mass spectrometry. Cuminol, eucarvone, and calamenene were
      common to these two sub-fractions, although the effects of these individual
      components were not determined. Taken together, these results suggest that C.
      obtusa oils promote hair growth in an animal model and a positive regulator of
      hair growth, VEGF, was induced by particular components of these oils.

PMID- 19576965
TI  - The distribution and characterization of endogenous protein arginine N
      methyltransferase 8 in mouse CNS.
AB  - Protein arginine N-methyltransferase (PRMT) 8 was first discovered from a
      database search for genes harboring four conserved methyltransferase motifs,
      which shares more than 80% homology to PRMT1 in amino acid [Lee J, Sayegh J,
      Daniel J, Clarke S, Bedford MT (2005) PRMT8, a new membrane-bound tissue-specific
      member of the protein arginine methyltransferase family. J Biol Chem 280:32890
      32896]. Interestingly, its tissue distribution is strikingly restricted to mouse
      CNS. To characterize the function in the CNS neurons, we raised an antiserum
      against PRMT8 to perform immunohistochemistry (IHC) and Western blot analysis. By
      IHC, the immunoreactivity of endogenous PRMT8 was broadly distributed in the CNS
      neurons with markedly intense signals in the cerebellum, hippocampal formation,
      and cortex, but was not detected in the cerebellar granular layer. In some subset
      of the neurons, the immunoreactivity was observed in the dendrites and axon
      bundles. The subcellular localization of the immunoreactivity was dominantly
      nuclear, arguing against the original report that exogenously expressed PRMT8
      localizes to the plasma membrane via the N-terminal myristoylation. A series of
      the exogenously expressed proteins with different in-frame translation initiation
      codons was tested for comparison with the endogenous protein in molecular size.
      The third initiator codon produced the protein that was equivalent in size to the
      endogenous and showed a similar localizing pattern in PC12 cells. In conclusion,
      PRMT8 is a neuron-specific nuclear enzyme and the N-terminus does not contain the
      glycine end for myristoylation target.

PMID- 19576969
TI  - Tannins and self-medication: Implications for sustainable parasite control in
      herbivores.
AB  - Animals adapt to the variability of the external environment and to their
      changing internal needs not only by generating homeostatic physiological
      responses, but also by operating in the external environment. In this study, we
      determined whether sheep with a gastrointestinal parasite infection increased
      intake of a low-quality food containing a natural antiparasitic agent (tannins)
      relative to non-parasitized sheep. Four groups of lambs (n=8 lambs/group) were
      assigned to a 2 x 2 factorial design with parasitic burden (P=parasites; NP=no
      parasites) and the offer of a supplement containing tannins (yes, no) as the main
      factors. Parasitized lambs ate more of the tannin-containing food than non
      parasitized lambs for the first 12 days of the study, when parasite burdens were
      high, but differences became smaller and disappeared toward the end of the study
      when parasite burdens decreased. This result suggests the lambs detected the
      presence of internal parasites or associated symptoms and modified their
      ingestion of an antiparasitic agent as a function of need.

PMID- 19576970
TI  - Chloroacetonitrile induces oxidative stress and apoptosis in mouse fetal liver.
AB  - Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking
      water. The present study was designed to investigate the potential adverse
      effects of maternal exposure to CAN on fetal liver in mice. Based on an initial
      dose-response experiment, CAN (25mg/(kgday)) was given orally to pregnant mice at
      gestation day (GD) 6, till GD 18. Fetuses were collected and fetal livers were
      used for assessing oxidative status, apoptosis and histopathological changes.
      Maternal exposure to CAN resulted in observed oxidative stress and redox
      imbalance in fetal liver tissues as marked by significant decrease in reduced
      glutathione (GSH) and elevation of oxidized glutathione (GSSG), malondialdehyde
      (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in genomic DNA. Further, CAN
      induced apoptosis as indicated by a significant increase in binding of Hoechst
      reagent to damaged DNA fragments of fetal liver and enhancement of the activity
      of caspase-3 in cytosolic fractions of fetal livers. Histopathological
      examination of fetal livers of CAN-treated mice showed hepatocytes with
      vacuolated cytoplasm, karyolysis and karyorrhexis as well as depletion of their
      glycogen content. In conclusion, maternal exposure to CAN adversely affects mouse
      fetal livers as evidenced by the induction of oxidative stress, apoptosis and
      histopathological changes.

PMID- 19576971
TI  - Investigations on the human hepatic cytochrome P450 isozymes involved in the
      metabolism of 3,4-methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine
      (BDB) enantiomers.
AB  - 3,4-Methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) are
      chiral designer drugs distributed on the illicit drug market and they are also N
      dealkyl metabolites of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy, Adam),
      3,4-methylenedioxyethylamphetamine (MDEA, Eve), and N-methyl-benzodioxolyl
      butanamine (MBDB, Eden), respectively. MDA and BDB are mainly metabolized via
      demethylenation to the corresponding catecholamines. The aim of the present work
      was to elucidate the contribution of the relevant human P450s in the
      demethylenation of the MDA and BDB enantiomers. They were incubated using
      heterologously expressed human P450s and the corresponding metabolites
      dihydroxyamphetamine and 1,2-dihydroxy-4-[2-amino-butyl]benzene were determined.
      Highest contributions to the demethylenation as calculated from the enzyme
      kinetic data were obtained for CYP2D6 (MDA and BDB) and additionally CYP3A4 in
      the case of BDB at substrate concentrations corresponding to plasma
      concentrations of recreational users. A preferred transformation of the S
      enantiomer could be observed for the CYP2D6- and CYP3A4-catalyzed reactions.

PMID- 19576966
TI  - Prozac during puberty: distinctive effects on neurogenesis as a function of age
      and sex.
AB  - Neurogenesis is a possible substrate through which antidepressants alleviate
      symptoms of depression. In adult male rodents and primates, chronic treatment
      with fluoxetine increases neurogenesis in the hippocampal formation. Little is
      known about the effects of the antidepressant on neurogenesis during puberty or
      in female animals at any age. Therefore we examined the effects of chronic
      fluoxetine treatment on cell proliferation and survival in male and female rats
      during puberty and adulthood. Adult and peri-pubescent male and female rats were
      treated chronically with fluoxetine (Prozac, 5 mg/kg) or saline. Subsequently
      rats received a single injection of 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg) to
      label DNA synthesis. Rats were sacrificed 2 h, 24 h, or 28 days after BrdU
      injection to examine cell proliferation, survival and cell fate. Fluoxetine
      increased cell proliferation in adult male rats but not in peri-pubescent males
      or female rats of any age or stage of the estrous cycle. Treatment did not alter
      the number of surviving cells in the male hippocampus but decreased survival in
      the female hippocampus. Thus, fluoxetine has distinctive effects on neurogenesis
      as a function of age and sex. Circulating levels of the stress hormone
      corticosterone were also examined. Treatment of female rats with fluoxetine
      during puberty decreased circulating levels of corticosterone in adults, even in
      the absence of the drug suggesting disruption of maturation of the hypothalamic
      pituitary-adrenal axis.

PMID- 19576972
TI  - Development of a new topical system: drug-in-cyclodextrin-in-deformable liposome.
AB  - A new delivery system for cutaneous administration combining the advantages of
      cyclodextrin inclusion complexes and those of deformable liposomes was developed,
      leading to a new concept: drug-in-cyclodextrin-in-deformable liposomes.
      Deformable liposomes made of soybean phosphatidylcholine (PC) or
      dimyristoylphosphatidylcholine (DMPC) and sodium deoxycholate as edge activator
      were compared to classical non-deformable liposomes. Liposomes were prepared by
      the film evaporation method. Betamethasone, chosen as the model drug, was
      encapsulated in the aqueous cavity of liposomes by the use of cyclodextrins.
      Cyclodextrins allow an increase in the aqueous solubility of betamethasone and
      thus, the encapsulation efficiency in liposome vesicles. Liposome size,
      deformability and encapsulation efficiency were calculated. The best results were
      obtained with deformable liposomes made of PC in comparison with DMPC. The
      stability of PC vesicles was evaluated by measuring the leakage of encapsulated
      calcein on the one hand and the leakage of encapsulated betamethasone on the
      other hand. In vitro diffusion studies were carried out on Franz type diffusion
      cells through polycarbonate membranes. In comparison with non-deformable
      liposomes, these new vesicles showed improved encapsulation efficiency, good
      stability and higher in vitro diffusion percentages of encapsulated drug. They
      are therefore promising for future use in ex vivo and in vivo experiments.

PMID- 19576973
TI  - Engineered chylomicron mimicking carrier emulsome for lymph targeted oral
      delivery of methotrexate.
AB  - The aim of the present study was to develop chylomicron mimicking carrier
      emulsome for oral lymphatic delivery of methotrexate (MTX), an anticancer drug.
      The compritol 888 ATO (CA) was used as lipid core and soya lecithin (PC) as
      stabilizer. The optimized emulsome (1:1.2 mole ratio of CA:PC) showed mean
      particle size of 160.3+/-10.2 nm and with 72.8+/-6.5% drug entrapment efficiency.
      The differential scanning calorimetric studies revealed a depression in
      endothermic onset for MTX loaded emulsome. The rapid burst release of the drug
      was observed in simulated gastric fluid (SGF pH 1.2) with significant increase in
      particle size of emulsome. However in simulated intestinal fluid (SIF, pH 7.4) a
      slow and consistent release of the drug was obtained over period of 24 h. Storage
      stability studies were performed at different temperatures (4+/-1 and 25+/-1
      degrees C) for 3 months which suggested that EML remain more stable when stored
      at refrigerated condition. The in vivo studies were carried out on albino rats
      and response was estimated collecting blood and lymph both. The pharmacokinetic
      parameters C(max), t(max) and AUC(0-->12h) after duodenal administration of
      optimized emulsomal formulation and plain MTX solution were 7.1 and 2.4
      microg/mL, 4 and 1 h, 40.45 and 7.2 h microg/mL respectively. The relative
      bioavailability of MTX was enhanced nearly 5.7 times with optimized EML
      formulation when compared to plain MTX solution with higher uptake and longer
      residence time of MTX molecules in lymphatics. Thus, emulsome could be used as
      lymphotropic carrier for delivery of bioactive(s) and hence for bioavailability
      enhancement.

PMID- 19576974
TI  - Prednisolone multicomponent nanoparticle preparation by aerosol solvent
      extraction system.
AB  - Prednisolone nanoparticles were prepared in the presence of a hydrophilic polymer
      and a surfactant by the aerosol solvent extraction system (ASES). A ternary
      mixture of prednisolone, polyethylene glycol (PEG), and sodium dodecyl sulfate
      (SDS) dissolved in methanol was sprayed through a nozzle into the reaction vessel
      filled with supercritical carbon dioxide. After the ASES process was repeated,
      precipitates of the ternary components were obtained by depressurizing the
      reaction vessel. When a methanolic solution of prednisolone/PEG 4000/SDS at a
      weight ratio of 1:6:2 was sprayed under the optimized ASES conditions, the mean
      particle size of prednisolone obtained after dispersing the precipitates in water
      was observed to be ca. 230 nm. Prednisolone nanoparticles were not obtained by
      the binary ASES process for prednisolone, in the presence of either PEG or SDS.
      Furthermore, ternary cryogenic cogrinding, as well as solvent evaporation, was
      not effective for the preparation of prednisolone nanoparticles. As the ASES
      process can be conducted under moderate temperature conditions, the ASES process
      that was applied to the ternary system appeared to be one of the most promising
      methods for the preparation of drug nanoparticles using the multicomponent
      system.

PMID- 19576975
TI  - Lipopolysaccharide contamination in intradermal DNA vaccination: toxic impurity
      or adjuvant?
AB  - PURPOSE: Lipopolysaccharides (LPS) are known both as potential adjuvants for
      vaccines and as toxic impurity in pharmaceutical preparations. The aim of this
      study was to assess the role of LPS in intradermal DNA vaccination administered
      by DNA tattooing. METHOD: Mice were vaccinated with a model DNA vaccine (Luc-NP)
      with an increasing content of residual LPS. The effect of LPS on systemic
      toxicity, antigen expression and cellular immunity was studied. RESULTS: The
      presence of LPS in the DNA vaccine neither induced systemic toxicity (as
      reflected by IL-6 concentration in serum), nor influenced antigen expression
      (measured by intravital imaging). Higher LPS contents however, appeared to be
      associated with an elevated cytotoxic T-lymphocyte (CTL) response but without
      reaching statistical significance. Interestingly, the DNA tattoo procedure by
      itself was shown to induce a serum cytokine response that was at least as potent
      as that induced by parenteral LPS administration. CONCLUSION: LPS does not show
      toxicity in mice vaccinated by DNA tattooing at dose levels well above those
      encountered in GMP-grade DNA preparations. Thus, residual LPS levels in the
      pharmaceutical range are not expected to adversely affect clinical outcome of
      vaccination trials and may in fact have some beneficial adjuvant effect. The
      observed pro-inflammatory effects of DNA tattoo may help explain the high
      immunogenicity of this procedure.

PMID- 19576976
TI  - Effect of wet milling process on the solid state of indomethacin and simvastatin.
AB  - The aim of this study was to investigate the effect of wet milling on the solid
      state of indomethacin (IMC) and simvastatin (SIM). Wet milling was performed
      using high pressure homogenization (HPH). Polyvinylpyrrolidone-K25 (PVP) and
      poloxamer 407 (P407) were used as suspension stabilizers. Samples were
      characterized before and after wet milling using particle size analyzer, scanning
      electron microscopy (SEM), infrared (IR) spectroscopy and modulated temperature
      differential scanning calorimetry (MTDSC) techniques. After wet milling of IMC,
      physical appearance and IR spectra indicated surface amorphization; however, the
      solid state of SIM remained unaffected. MTDSC could not detect surface
      amorphization in IMC, suggesting that if present, it was only at very low levels.
      These results are in contradiction to the previous reports where dry milling of
      IMC and SIM resulted in amorphization of crystalline particles. Moreover,
      cryogrinding of IMC in the absence of water resulted in an amorphous form while
      presence of water using the same cryogrinding conditions resulted in a solid
      state similar to that obtained after wet milling. These results signify the role
      of water in inhibiting the amorphization during wet milling of crystalline drugs.

PMID- 19576977
TI  - Applications of NIR in early stage formulation development. Part II. Content
      uniformity evaluation of low dose tablets by principal component analysis.
AB  - A near infrared method based on principal component analysis (PCA) was developed
      for predicting content uniformity of low dose tablets manufactured by a direct
      compression process. The work was conducted in early stage formulation
      development. NIR spectra of one hundred and eighty tablets from three feasibility
      batches were used as the pseudo-calibration set. A correlation was established
      between PCA scores and a set of reference values obtained by HPLC analysis. The
      reference values were also used to define a concentration range for the active
      pharmaceutical ingredient to facilitate content uniformity prediction by PCA.
      Analyses of unknown samples were conducted by forming a prediction set that
      included the calibration and unknown samples, followed by PCA. Samples from two
      development batches were predicted using the PCA model and the results were
      consistent with the reference HPLC values. Remarkably, the model was able to
      predict CU for tablets that were prepared using different grades of lactose
      (anhydrous versus monohydrate). Additionally, during this study, the impact of
      spectrum pretreatments on PCA is demonstrated. A brief discussion is given to
      highlight the advantages of PCA over partial least squares (PLS) regression for
      analysis of samples generated in early stage formulation development.

PMID- 19576978
TI  - Physico-chemical analysis of metronidazole encapsulation processes in Eudragit
      copolymers and their blending with amphiphilic block copolymers.
AB  - A physico-chemical analysis of metronidazole-Eudragit copolymers L100 and RLPO (a
      cationic polymeric matrix with an electrophilic character) was carried out in
      order to explore the drug-polymer interaction and its possible effects on the
      encapsulation and release profiles. An oil-in-oil encapsulation procedure was
      designed to obtain more intimate drug-matrix mixtures and to obtain a better
      insight into the details of the interaction. The encapsulation efficiency
      obtained in these cases was high (in the range of 85-95%), but the release rates
      were quite rapid. Solubility and interaction between metronidazole and copolymers
      are discussed in detail with a view to explaining the results. Amphiphilic block
      copolymers of poly(ethylene)-b-(polyethylene oxide) (20, 50 and 80% PEO) were
      tested as a matrix for metronidazole release in order to improve drug profiles.
      The performance of RLPO as the matrix for drug release was improved by blending
      it with amphiphilic block copolymer poly(ethylene)-b-(polyethylene oxide) (20%
      PEO). The release mechanism of metronidazole is governed mainly by the swelling
      of RLPO, yielding a better fit with the second-order Schott equation.

PMID- 19576979
TI  - Meeting commentary--formulating better medicines for children.

PMID- 19576980
TI  - Analgesic and anti-inflammatory activities of ethanol root extract of Mahonia
      oiwakensis in mice.
AB  - AIMS OF THE STUDY: This study investigated the anti-inflammatory and analgesic
      activities, and protoberberine alkaloid contents of ethanol extract of MO roots
      (MOR(EtOH)). MATERIALS AND METHODS: The analgesic activity of MOR(EtOH) was
      determined using acetic acid-induced writhing response and formalin test. The
      anti-inflammatory activity of MOR(EtOH) was determined using the lambda
      carrageenan-induced paw oedema model. The protoberberine alkaloid contents of
      MOR(EtOH) were identified by high-performance liquid chromatography (HPLC).
      RESULTS: MOR(EtOH) (100 and 500 mg/kg) decreased the acetic acid-induced writhing
      responses and licking times of the second phase in the formalin test. Moreover,
      carrageenan-induced paw oedema was significantly reduced in a dose-dependent
      manner by administering MOR(EtOH) (100 and 500 mg/kg) at 3, 4, and 5h after the
      carrageenan injection. The serum levels of tumor necrosis factor-alpha (TNF
      alpha) and nitric oxide (NO) of MOR(EtOH)-treated mice were significantly reduced
      compared with those in the serum of animals administered carrageenan. Notably,
      MOR(EtOH) attenuated the expression of cyclo-oxygenase 2 (COX-2) and inducible
      nitric oxide synthase (iNOS) and neutrophil infiltration in paw tissues injected
      with carrageenan. The anti-inflammatory mechanisms of MOR(EtOH) appear to be
      related to the inhibition of neutrophil infiltration, iNOS and COX-2 protein
      expression, NO release, and the decreasing TNF-alpha level in serum. The
      analytical results showed that the contents of berberine, palmatine and
      jatrorrhizine were 191.45 mg/g extract, 100.15 mg/g extract and 66.45 mg/g
      extract, respectively. CONCLUSION: These experimental results suggest that
      MOR(EtOH) produced both analgesic and anti-inflammatory effects in mice and may
      be a candidate for the development of pharmacological agents used in the
      treatment of inflammatory disorders.

PMID- 19576982
TI  - Sorting nexin 3, a protein upregulated by lithium, contains a novel
      phosphatidylinositol-binding sequence and mediates neurite outgrowth in N1E-115
      cells.
AB  - Lithium, a drug in the treatment of bipolar disorder, modulates many aspects of
      neuronal developmental processes such as neurogenesis, survival, and
      neuritogenesis. However, the underlying mechanism still remains to be understood.
      Here, we show that lithium upregulates the expression of sorting nexin 3 (SNX3),
      one of the Phox (PX) domain-containing proteins involved in endosomal sorting,
      and regulates neurite outgrowth in mouse N1E-115 neuroblastoma cells. The
      inhibition of SNX3 function by its knockdown decreases lithium-induced outgrowth
      of neurites. Transfection of the full-length SNX3 construct into cells
      facilitates the outgrowth. We also find that the C-terminus, as well as the PX
      domain, of SNX3 has a functional binding sequence with phosphatidylinositol
      monophosphates. Transfection of the C-terminal deletion mutant or only the C
      terminus does not have an effect on the outgrowth. These results suggest that
      SNX3, a protein upregulated by lithium, is an as yet unknown regulator of neurite
      formation and that it contains another functional phosphatidylinositol phosphate
      binding region at the C-terminus.

PMID- 19576981
TI  - A 4-oxo-2(E)-nonenal-derived glutathione adduct from 15-lipoxygenase-1-mediated
      oxidation of cytosolic and esterified arachidonic acid.
AB  - 15(S)-Hydroperoxy-[5Z,8Z,11Z,13E]-eicosatetraenoic acid (15(S)-HpETE) undergoes
      homolytic decomposition to bifunctional electrophiles such as 4-oxo-2(E)-nonenal.
      4-Oxo-2(E)-nonenal reacts with glutathione to form a thiadiazabicyclo-4-oxo-2(E)
      nonenal-glutathione adduct (TOG). Therefore, this endogenous glutathione adduct
      can serve as a specific biomarker of lipid hydroperoxide-mediated 4-oxo-2(E)
      nonenal formation. A monocyte/macrophage cell line was generated to
      constitutively express human 15-lipoxygenase-1. In these cells, TOG was formed
      from 15(S)-HpETE-derived 4-oxo-2(E)-nonenal in a nonlinear dose-dependent manner
      upon arachidonic acid treatment. The lipoxygenase inhibitor cinnamyl-3,4
      dihydroxy-alpha-cyanocinnamate abolished arachidonic acid-mediated TOG formation.
      The calcium ionophore A23187 was also used to induce the formation of 15(S)-HpETE
      from esterified arachidonic acid present in the membrane lipids. In the 15
      lipoxygenase-1-expressing cells, the calcium ionophore A23187 significantly
      increased TOG levels compared with mock-transfected cells. This was due to the 15
      lipoxygenase-mediated formation of 15(S)-HpETE in the forms of free fatty acid
      and esterified lipids, which was subsequently converted to 4-oxo-2(E)-nonenal.
      The increase in TOG formation was again abrogated by pretreatment with cinnamyl
      3,4-dihydroxy-alpha-cyanocinnamate. Only 8.7% 15(S)-HETE (both the free fatty
      acid and its esterified form in the cell membrane) was formed after ionophore
      A23187 stimulation compared with that formed after the addition of arachidonic
      acid. In contrast, the TOG levels after treatment with ionophore A23187 or
      arachidonic acid were comparable. Thus, it is likely that esterified 15(S)-HpETE
      underwent homolytic decomposition to 4-oxo-2(E)-nonenal more efficiently than the
      free 15(S)-HpETE that was formed in the cytosol.

PMID- 19576983
TI  - Begin at the beginning: evolution of translational initiation.
AB  - Initiation of protein synthesis, entailing ribosomal recognition of the mRNA
      start codon and setting of the correct reading frame, is the rate-limiting step
      in translation and the main target of translation regulation in all modern cells.
      As efficient selection of the translation start site is vital for survival of
      extant cells, a mechanism for ensuring this may already have been in existence in
      the last universal common ancestor of present-day cells. This article reviews
      known features of the molecular machinery for initiation in the primary domains
      of life, Bacteria, Archaea and Eukarya, and attempts to identify conserved
      features that may be useful for reconstructing a model of the ancestral
      initiation apparatus.

PMID- 19576984
TI  - Synthesis, characterization and evaluation of thiolated quaternary ammonium
      chitosan conjugates for enhanced intestinal drug permeation.
AB  - In a previous report quaternary ammonium-chitosan conjugates (N(+)-Chs) endowed
      with intestinal drug permeability-enhancing properties were described. They are
      characterized by short pendant chains of n adjacent diethyl-dimethylene-ammonium
      groups substituted onto the primary amino group of the chitosan (Ch) repeating
      units. In the present work two N(+)-Chs, one having DS (degree of
      substitution)=59.2+/-4.5%, n=1.7+/-0.1 (N(+)(60)-Ch), the other one having
      DS=40.6+/-1.3%, n=3.0+/-0.2 (N(+)(40)-Ch) were used to synthesize novel
      multifunctional non-cytotoxic Ch derivatives, each carrying thiol along with
      quaternary ammonium groups (N(+)-Ch-SH), with increased potential to enhance
      transepithelial drug transport. They have been obtained by transforming the
      residual free amino groups of N(+)(60)-Ch and N(+)(40)-Ch into 3
      mercaptopropionamide moieties. The former yielded 4.5+/-0.7% thiol-bearing
      groups, the latter, 5.2+/-1.1% of such groups, on a Ch repeating unit basis. The
      multifunctional derivatives have improved the ability of the parent N(+)-Chs to
      enhance the permeability of the water-soluble macromolecular fluorescein
      isothiocyanate dextran, MW 4400 Da (FD4) and that of the lipophilic dexamethasone
      (DMS) across the excised rat intestinal mucosa and Caco-2 cell monolayer,
      respectively. The data from the present work altogether point to a synergism of
      quaternary ammonium and thiol groups to improve the intestinal drug absorption
      enhancing properties of the multifunctional Ch derivatives.

PMID- 19576985
TI  - Occurrence of fungi in combs of fungus-growing termites (Isoptera: Termitidae,
      Macrotermitinae).
AB  - Fungus-growing termites cultivate their mutualistic basidiomycete Termitomyces
      species on a substrate called a fungal comb. Here, the Suicide Polymerase
      Endonuclease Restriction (SuPER) method was adapted for the first time to a
      fungal study to determine the entire fungal community of fungal combs and to test
      whether fungi other than the symbiotic cultivar interact with termite hosts. Our
      molecular analyses show that although active combs are dominated by Termitomyces
      fungi isolated with direct Polymerase Endonuclease Restriction - Denaturing
      Gradient Gel Electrophoresis (PCR-DGGE), they can also harbor some filamentous
      fungi and yeasts only revealed by SuPER PCR-DGGE. This is the first molecular
      evidence of the presence of non-Termitomyces species in active combs. However,
      because there is no evidence for a species-specific relationship between these
      fungi and termites, they are mere transient guests with no specialization in the
      symbiosis. It is however surprising to notice that termite-associated Xylaria
      strains were not isolated from active combs even though they are frequently
      retrieved when nests are abandoned by termites. This finding highlights the
      implication of fungus-growing termites in the regulation of fungi occurring
      within the combs and also suggests that they might not have any particular
      evolutionary-based association with Xylaria species.

PMID- 19576986
TI  - Characterization of endogenous and recombinant forms of laccase-2, a multicopper
      oxidase from the tobacco hornworm, Manduca sexta.
AB  - Laccases belong to the group of multicopper oxidases that exhibit wide substrate
      specificity for polyphenols and aromatic amines. They are found in plants, fungi,
      bacteria, and insects. In insects the only known role for laccase is in cuticle
      sclerotization. However, extracting laccase from the insect's cuticle requires
      proteolysis, resulting in an enzyme that is missing its amino-terminus. To
      circumvent this problem, we expressed and purified full-length and amino
      terminally truncated recombinant forms of laccase-2 from the tobacco hornworm,
      Manduca sexta. We also purified the endogenous enzyme from the pharate pupal
      cuticle and used peptide mass fingerprinting analysis to confirm that it is
      laccase-2. All three enzymes had pH optima between 5 and 5.5 when using N
      acetyldopamine (NADA) or N-beta-alanyldopamine-alanyldopamine (NBAD) as
      substrates. The laccases exhibited typical Michaelis-Menten kinetics when NADA
      was used as a substrate, with K(m) values of 0.46 mM, 0.43 mM, and 0.63 mM,
      respectively, for the full-length recombinant, truncated recombinant, and
      cuticular laccases; the apparent k(cat) values were 100 min(-1), 80 min(-1), and
      290 min(-1). The similarity in activity of the two recombinant laccases suggests
      that laccase-2 is expressed in an active form rather than as a zymogen, as had
      been previously proposed. This conclusion is consistent with the detection of
      activity in untanned pupal wing cuticle using the laccase substrate 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Immunoblot analysis of
      proteins extracted from both tanned and untanned cuticle detected only a single
      protein of 84 kDa, consistent with the full-length enzyme. With NBAD as
      substrate, the full-length recombinant and cuticular laccases showed kinetics
      indicative of substrate inhibition, with K(m) values of 1.9 mM and 0.47 mM,
      respectively, and apparent k(cat) values of 200 min(-1) and 180 min(-1). These
      results enhance our understanding of cuticle sclerotization, and may aid in the
      design of insecticides targeting insect laccases.

PMID- 19576989
TI  - Withdrawn: Feedback Related Negativity Reflects Not Feedback Evaluation But
      Conflict Detection, An ERP Study.

PMID- 19576988
TI  - Purification of an active, oligomeric chitin synthase complex from the midgut of
      the tobacco hornworm.
AB  - Chitin formation depends on the activity of a family II glycosyltransferase known
      as chitin synthase, whose biochemical and structural properties are largely
      unknown. Previously, we have demonstrated that the chitin portion of the
      peritrophic matrix in the midgut of the tobacco hornworm, Manduca sexta, is
      produced by chitin synthase 2 (CHS-2), one of two isoenzymes encoded by the Chs-1
      and Chs-2 genes (also named Chs-A and Chs-B), and that CHS-2 is located at the
      apical tips of the brush border microvilli. Here we report the purification of
      the chitin synthase from the Manduca midgut as monitored by its activity and
      immuno-reactivity with antibodies to the chitin synthase. After gel permeation
      chromatography, the final step of the developed purification protocol, the active
      enzyme eluted in a fraction corresponding to a molecular mass between 440 and 670
      kDa. Native PAGE revealed a single, immuno-reactive band of about 520 kDa, thrice
      the molecular mass of the chitin synthase monomer. SDS-PAGE and immunoblotting
      indicated finally that an active, oligomeric complex of the chitin synthase was
      purified. In summary, the chitin synthase from the midgut of Manduca may prove to
      be a good model for investigating the enzymes' mode of action.

PMID- 19576987
TI  - An insight into the transcriptome and proteome of the salivary gland of the
      stable fly, Stomoxys calcitrans.
AB  - Adult stable flies are blood feeders, a nuisance, and mechanical vectors of
      veterinary diseases. To enable efficient feeding, blood sucking insects have
      evolved a sophisticated array of salivary compounds to disarm their host's
      hemostasis and inflammatory reaction. While the sialomes of several blood sucking
      Nematocera flies have been described, no thorough description has been made so
      far of any Brachycera, except for a detailed proteome analysis of a tabanid (Xu
      et al., 2008). In this work we provide an insight into the sialome of the muscid
      Stomoxys calcitrans, revealing a complex mixture of serine proteases,
      endonucleases, Kazal-containing peptides, anti-thrombins, antigen 5 related
      proteins, antimicrobial peptides, and the usual finding of mysterious secreted
      peptides that have no known partners, and may reflect the very fast evolution of
      salivary proteins due to the vertebrate host immune pressure. Supplemental Tables
      S1 and S2 can be downloaded from
      http://exon.niaid.nih.gov/transcriptome/S_calcitrans/T1/Sc-tb1-web.xls and
      http://exon.niaid.nih.gov/transcriptome/S_calcitrans/T2/Sc-tb2-web.xls.

PMID- 19576990
TI  - Expression, purification and characterization of a functional extracellular
      domain of porcine FcgammaRII.
AB  - FcgammaRs are involved in regulating a multitude of innate and adaptive immune
      responses, which makes them attractive targets for the development of novel
      immunotherapeutic approaches. In this report, we describe a simple method for the
      production of a large quantity of recombinant porcine FcgammaRII. The
      extracellular domain of the porcine FcgammaRII (poFcgammaRII) gene was
      constructed and cloned into the Escherichiacoli expression vector pET-28a. The
      recombinant protein was expressed at high level in E. coil BL21 (DE3) and existed
      mainly as inclusion bodies. The inclusion bodies were solubilized in 6M guanidine
      hydrochloride and purified by Ni-chelation, and refolded by rapid dilution. After
      purification and renaturation, the recombinant soluble protein (rsFcgammaRII)
      coated on high-binding ELISA plates, showed concentration dependent binding of
      porcine IgG and the binding of porcine IgG to the surface bound rsFcgammaRII was
      inhibited in a dose-dependent manner by soluble rsFcgammaRII itself. Then by the
      inhibition assay we evaluated the effectiveness of the rsFcgammaRII in inhibiting
      the IgG binding to the whole molecule of poFcgammaRII expressed on the Marc-145
      cell surface, the rsFcgammaRII inhibited the binding of porcine IgG to the
      transfected Marc-145 cell's surface, with an IC(50) value of 0.87 microM,
      demonstrating that rsFcgammaRII manifests the similar specificity as native
      poFcgammaRII. The method for highly efficient production of biologically active
      poFcgammaRII may be employed for both basic research and potential clinical
      applications.

PMID- 19576991
TI  - Attention effects on sensory gating--intracranial and scalp recordings.
AB  - The function of sensory gating is usually studied in paired-click experiments and
      quantified by the decrease of the event-related potential (ERP) component P50 and
      other ERP components from the 1st to the 2nd stimuli. The impact of attention on
      these gating measures is still not fully resolved. In the current study, the
      impact of attention on sensory gating was studied by scalp and intracranial
      recordings. The study sample consisted of epilepsy and tumor patients undergoing
      presurgical evaluation by means of implanted electrodes. In the unattend
      condition, patients had no overt task. In the active condition, patients had to
      count simultaneously trials with paired clicks, as well as interspersed trials
      with single clicks. The ERPs in the active condition were characterized by an
      underlying negativity both for scalp and neocortical recordings, reaching their
      maximum at the N100 latency of the 2nd stimulus. A time-frequency analysis
      revealed that this attention effect comprised only low frequency signals (<3 Hz).
      In line with that, P50 amplitude and P50 gating were unaffected by attention when
      data were filtered from 10 to 50 Hz. In addition, attention effects were revealed
      for intrahippocampal ERP components and for induced high frequency neocortical
      gamma band activity. Findings indicate that N100 and P200 gating measures can
      potentially be affected by attention and have to be interpreted carefully when
      studying clinical populations.

PMID- 19576992
TI  - Neural mechanisms of concurrent stimulus processing in dual tasks.
AB  - Little is known about how the human brain processes multiple relevant information
      streams competing for behavior. The present study aimed at specifying the
      interaction of the lateral prefrontal cortex (lPFC) with task-relevant sensory
      brain regions during concurrent stimulus processing of two relevant stimuli (S1,
      S2) in a classical dual-task situation. In detail, we tested whether S1
      processing is independent of the task relevance of S2 as has been hypothesised in
      cognitive theories on dual-task processing. Using functional Magnetic Resonance
      Imaging, we tested two neural mechanisms that might reflect effects of S2
      relevance on S1 processing at different temporal overlaps. The results indicate
      that: (1) activity amplitudes in S1-relevant regions in the inferior temporal
      cortex were similarly affected by the temporal overlap between the two stimuli
      when S2 was relevant or irrelevant and (2) only when S2 was relevant in the dual
      task, significant increases in the functional coupling between S1-relevant
      regions and dual-task-related regions in the posterior lPFC were present at high
      temporal overlap. No similar effects were found for S2-relevant regions. These
      findings suggest that concurrent stimulus processing in dual tasks is realised by
      transient changes in functional coupling for stimuli with relatively higher
      priority (S1).

PMID- 19576993
TI  - Phylogenetic relationships of flowerpeckers (Aves: Dicaeidae): novel insights
      into the evolution of a tropical passerine clade.
AB  - Understanding the relationships and evolution of flowerpeckers has been
      challenging, particularly as no phylogenetic study has as yet assessed the group.
      Here, we present a first such analysis of this clade based on sequences of two
      mitochondrial genes and one nuclear intron. Our analyses offer strong support for
      monophyly of the Dicaeidae. Within the family, 4 Dicaeum species (D.
      chrysorrheum, D. melanoxanthum, D. agile, and D. everetii) had closer affinity to
      Prionochilus, although tests of alternative topologies could not reject
      reciprocal monophyly of the two genera. Across the family, overall bill shape
      trends from more stout bills basally to more slender and medium bills, whereas
      sexual dichromatism and plumage patterns show much more homoplasy. Taxonomically,
      generic allocations may need to be changed to reflect historical relationships
      better.

PMID- 19576994
TI  - A new Indo-Malayan member of the Stenostiridae (Aves: Passeriformes) revealed by
      multilocus sequence data: biogeographical implications for a morphologically
      diverse clade of flycatchers.
AB  - Recent molecular studies on passerine birds have highlighted numerous
      discrepancies between traditional classification and the phylogenetic
      relationships recovered from sequence data. Among the traditional families that
      were shown to be highly polyphyletic are the Muscicapidae Old World flycatcher.
      This family formerly included all Old World passerines that forage on small
      insects by performing short sallies from a perch. Genera previously allocated to
      the Muscicapidae are now thought to belong to at least seven unrelated lineages.
      While the peculiarity of most of these lineages has been previously recognized by
      Linnean classification, usually at the rank of families, one, the so-called
      Stenostiridae, a clade comprising three Afrotropical and Indo-Malayan genera, has
      only recently been discovered. Here, we address in greater detail the
      phylogenetic relationships and biogeographic history of the Stenostiridae using a
      combination of mitochondrial and nuclear data. Our analyses revealed that one
      species, Rhipidura hypoxantha, previously attributed to the Rhipiduridae
      (fantails), is in fact a member of the Stenostiridae radiation and sister to the
      South African endemic genus Stenostira (Fairy Flycatcher). Our dating analyses,
      performed in a relative-time framework, suggest that the splits between
      Stenostira/R. hypoxantha and Culicicapa/Elminia occurred synchronously. Given
      that the Stenostiridae assemblage has been consistently recovered by independent
      studies, we clarify its taxonomic validity under the rules of the International
      Code of Zoological Nomenclature.

PMID- 19576995
TI  - Relationship between the resistance to bile salts and low pH with
      exopolysaccharide (EPS) production of Bifidobacterium spp. isolated from infants
      feces and breast milk.
AB  - The purpose of this study was to investigate a possible relation between
      resistance to bile salts and low pH with exopolysaccharide (EPS) producing of
      Bifidobacterium spp. In this study, a total of 31 Bifidobacterium spp. were
      isolated from breast fed infants feces and breast milk samples. As a result of
      the identification tests, isolates were identified as Bifidobacterium breve (15
      strains), B. bifidum (11 strains), B. pseudocatenulatum (3 strains) and B. longum
      (2 strains). Bifidobacterium spp. were determined exopolysaccharide (EPS)
      production. EPS productions observed at chance rations (38.00-97.64 mg/l) among
      of Bifidobacterium spp. Furthermore, Bifidobacterium spp. were determined
      resistance to bile salts and low pH. Positive correlations between production of
      exopolysaccharide and resistance to bile salts (p<0.01) or low pH (p<0.01) were
      found Bifidobacterium spp. This investigation showed that high EPS production of
      Bifidobacteria may be important in the selection of probiotic strains for
      resistance to bile salts and low pH.

PMID- 19576996
TI  - Elimination of marker genes from transformed filamentous fungi by unselected
      transient transfection with a Cre-expressing plasmid.
AB  - A convenient method to remove selectable markers from fungal transformants
      permits the markers to be used for sequential transformations, and should also
      reduce public concerns and regulatory impediments to applications involving
      environmental release of genetically modified fungi. We report a method for
      marker removal that requires no genetic selection. Protoplasts from Neotyphodium
      coenophialum,Neotyphodium uncinatum and Epichloe festucae transformants
      containing a hygromycin B phosphotransferase gene (hph) flanked by loxP sites in
      direct orientation were transiently transfected with a Cre-recombinase expression
      plasmid, and then cultured without selection. The marker was eliminated in 0.5-2%
      of the colonies, leaving a single loxP sequence and no other exogenous DNA in the
      genome. This approach was also applied to the yA gene of Aspergillus nidulans as
      a laboratory exercise to demonstrate multiple principles of transformation and
      genome manipulation. Thus, the Cre-expression plasmid and transient transfection
      approach was rapid, flexible and useful for diverse filamentous fungi.

PMID- 19576997
TI  - Phosphorylation regulates copper-responsive trafficking of the Menkes copper
      transporting P-type ATPase.
AB  - The Menkes copper-translocating P-type ATPase (ATP7A) is a critical copper
      transport protein functioning in systemic copper absorption and supply of copper
      to cuproenzymes in the secretory pathway. Mutations in ATP7A can lead to the
      usually lethal Menkes disease. ATP7A function is regulated by copper-responsive
      trafficking between the trans-Golgi Network and the plasma membrane. We have
      previously reported basal and copper-responsive kinase phosphorylation of ATP7A
      but the specific phosphorylation sites had not been identified. As copper
      stimulates both trafficking and phosphorylation of ATP7A we aimed to identify all
      the specific phosphosites and to determine whether trafficking and
      phosphorylation are linked. We identified twenty in vivo phosphorylation sites in
      the human ATP7A and eight in hamster, all clustered within the N- and C-terminal
      cytosolic domains. Eight sites were copper-responsive and hence candidates for
      regulating copper-responsive trafficking or catalytic activity. Mutagenesis of
      the copper-responsive phosphorylation site Serine-1469 resulted in
      mislocalization of ATP7A in the presence of added copper in both polarized (Madin
      Darby canine kidney) and non-polarized (Chinese Hamster Ovary) cells, strongly
      suggesting that phosphorylation of specific serine residues is required for
      copper-responsive ATP7A trafficking to the plasma membrane. A constitutively
      phosphorylated site, Serine-1432, when mutated to alanine also resulted in
      mislocalization in the presence of added copper in polarized Madin Darby kidney
      cells. These studies demonstrate that phosphorylation of specific serine residues
      in ATP7A regulates its sub-cellular localization and hence function and will
      facilitate identification of the kinases and signaling pathways involved in
      regulating this pivotal copper transporter.

PMID- 19576998
TI  - The complexity of the GABAA receptor shapes unique pharmacological profiles.
AB  - Gamma-amino butyric acid (GABA) is the most abundant inhibitory neurotransmitter
      in the central nervous system (CNS) and many physiological actions are modulated
      by GABA(A) receptors. These chloride channels can be opened by GABA and are a
      target for a variety of important drugs such as benzodiazepines, barbiturates,
      neuroactive steroids, convulsants and anaesthetics. GABA(A) receptors are
      involved in anxiety, feeding and drinking behaviour, circadian rhythm, cognition,
      vigilance, and learning and memory. Moreover, deficits in the functional
      expression of GABA(A) receptors have been implicated in multiple neurological and
      psychiatric diseases. This review aims to discuss the unique physiological and
      pharmacological properties of the multitude of GABA(A) receptor subtypes present
      in the CNS, making this receptor an important target for novel rational drug
      therapy.

PMID- 19576999
TI  - FN3: a new protein scaffold reaches the clinic.
AB  - In the ten years since the first fibronectin type III (FN3) domain library was
      published, FN3 has continued to show promise as a scaffold for the generation of
      stable protein domains that bind to targets with high affinity. A variety of
      display systems, library designs and affinity maturation strategies have been
      used to generate FN3 domains with nanomolar to picomolar affinities. The first
      crystal structures of engineered FN3 molecules in complex with their targets have
      been solved, and structural studies of engineered FN3 have begun to reveal
      determinants of stability and to define zones that accept mutations with minimal
      trade-off between affinity and stability. CT-322, the first engineered FN3 to
      enter clinical development, is now entering Phase II trials for glioblastoma
      multiforme.

PMID- 19577000
TI  - Histone acetyl transferases as emerging drug targets.
AB  - Post-translational modifications, such as acetylation or phosphorylation, play a
      crucial role in the regulation of gene transcription in eukaryotes. Different
      subtypes of histone acetyl transferases (HATs) catalyze the acetylation of
      histones on specific lysine residues. A potential role of HATs in the pathology
      of cancer, asthma, COPD and viral infection has been described. This indicates
      that specific HAT inhibitors are potential tools for pharmacological research and
      might find therapeutic applications. This review focuses on the role of the HATs
      p300, CBP, PCAF and GCN5 in different diseases and the development of small
      molecule inhibitors of these enzymes as potential drugs.

PMID- 19577002
TI  - Allium cepa test in environmental monitoring: a review on its application.
AB  - Higher plants are recognized as excellent genetic models to detect environmental
      mutagens and are frequently used in monitoring studies. Among the plant species,
      Alium cepa has been used to evaluate DNA damages, such as chromosome aberrations
      and disturbances in the mitotic cycle. Employing the A. cepa as a test system to
      detect mutagens dates back to the 40s. It has been used to this day to assess a
      great number of chemical agents, which contributes to its increasing application
      in environmental monitoring. The A. cepa is characterized as a low cost test. It
      is easily handled and has advantages over other short-term tests that require
      previous preparations of tested samples, as well as the addition of exogenous
      metabolic system. Higher plants, even showing low concentrations of oxidase
      enzymes and a limitation in the substrate specification in relation to other
      organism groups, present consistent results that may serve as a warning to other
      biological systems, since the target is DNA, common to all organisms. The A. cepa
      test also enables the evaluation of different endpoints. Among the endpoints,
      chromosome aberrations have been the most used one to detect genotoxicity along
      the years. The mitotic index and some nuclear abnormalities are used to evaluate
      citotoxicity and analyze micronucleus to verify mutagenicity of different
      chemicals. Moreover, the A. cepa test system provides important information to
      evaluate action mechanisms of an agent about its effects on the genetic material
      (clastogenic and/or aneugenic effects). In the face of all the advantages that
      the A. cepa test system offers, it has been widely used to assess the impacts
      caused by xenobiotics, characterizing an important tool for environmental
      monitoring studies, where satisfactory results have been reported.

PMID- 19577003
TI  - Early inhibition of EGFR signaling prevents diabetes-induced up-regulation of
      multiple gene pathways in the mesenteric vasculature.
AB  - Diabetes mellitus is associated with vascular complications including an
      impairment of vascular function and alterations in the reactivity of blood
      vessels to vasoactive hormones. However, the signaling mechanisms leading to
      vascular dysfunction in diabetes are not fully understood. This microarray-based
      study was designed to identify differential gene expression between the normal
      and diabetic mesenteric vasculature and to investigate the effect of inhibiting
      epidermal growth factor receptor (EGFR) signaling on global gene expression in
      the mesenteric bed of streptozotocin (STZ)-induced diabetic rats. Transcriptome
      analysis was performed in triplicate using oligonucleotide microarrays housing
      10,000 rat genes on the mesenteric bed of normal, diabetic, and diabetic rats
      treated with AG1478, a selective inhibitor of EGFR. Four weeks of diabetes led to
      a profound alteration in gene expression within the mesenteric bed with 1167 of
      the 3074 annotated genes being up-regulated and 141 genes down-regulated by at
      least 2-fold. The up-regulated gene ontologies included receptor tyrosine
      kinases, G-protein coupled receptors and ion channel activity. In particular,
      significant overexpressions of colipase, phospholipase A2, carboxypeptidases, and
      receptor tyrosine kinases such as EGFR, erbB2 and fibroblast growth factor
      receptor were observed in diabetes mesenteric vasculature. A 4-week
      intraperitoneal treatment of diabetic animals with AG1478 (1.2 mg/kg/alt diem)
      beginning on the same day as STZ injection prevented up-regulation of the
      majority (approximately 95%) of the genes associated with STZ diabetes including
      those apparently "unrelated" to the known EGFR pathway without correction of
      hyperglycemia. These results suggest that activation of EGFR signaling is a key
      initiating step that leads to induction of multiple signaling pathways in the
      development of diabetes-induced vascular dysfunction. Thus, therapeutic targeting
      of EGFR may represent a novel strategy for the prevention and/or treatment of
      vascular dysfunction in diabetes.

PMID- 19577004
TI  - TW96, a synthetic 1,4-naphthoquinone, differentially regulates vascular and
      endothelial cells survival.
AB  - Vascular smooth muscle cell (VSMCs) proliferation is an essential factor in
      cardiovascular diseases, such as primary atherosclerosis and in-stent restenosis.
      In this study, we examined the effects of the novel synthetic naphthoquinone, 2
      pyrrilidino-3-(p-hydroxyphenylamino)-1,4-naphthoquinone (TW-96), on cultured
      VSMCs and endothelial cells (ECs). Pharmacological concentrations of the
      derivative TW96 were found to induce VSMCs death, probably by increasing ROS
      levels while decreasing mitochondrial potential (DeltaPsi(m)) without affecting
      ECs. Treatment of tissue cultures with ROS is known to induce MAPK activity. Our
      observations showed prolonged phosphorylation and perinuclear accumulation of
      ERK1/2 and p38 simultaneously with an inhibition of MKP1. Increased expression of
      Bax found in TW96-stimulated VSMCs was inhibited by the NADPH oxidase inhibitor
      diphenyliodonium (DPI). An examination of the suppressive effects of TW96 on PDGF
      BB-stimulated VSMCs cycle progression showed that TW96 leads to migration arrest
      at concentrations lower than LC(50). We hope that this prototype derivative will
      establish the basis for creating more specific naphthoquinone derivatives aimed
      at preventing the VSMCs proliferation associated with stenosis and restenosis.

PMID- 19577005
TI  - Do we know what patients want? The doctor-patient communication gap in functional
      gastrointestinal disorders.
AB  - BACKGROUND & AIMS: Understanding patients' expectations at initial consultation
      for functional gastrointestinal disorders (FGIDs) might influence future health
      care utilization. Ideally, patients and doctors would have a common understanding
      of the issues involved. We sought to investigate this with matched
      questionnaires. METHODS: Patients' needs/expectations/understanding were compared
      with gastroenterologists' and general practitioners' awareness of these. Patients
      were followed up to investigate satisfaction with and outcomes of specialist
      consultation. RESULTS: Specialists underestimated the number and severity of
      patients' symptoms (in 43% and 41%, respectively), and patients and specialists
      had quite discordant views on what treatment would best suit their symptoms.
      Strikingly, only 1 of 13 patients available for follow-up agreed with or accepted
      the functional diagnosis, despite all being diagnosed by a specialist as having
      an FGID. CONCLUSIONS: In FGIDs there is a communication gap between patients and
      gastroenterologists. Importantly, at follow-up, patients do not acknowledge their
      FGID diagnosis. This communication gap and lack of acceptance of a functional
      diagnosis are likely to influence future management and health care utilization.

PMID- 19577006
TI  - International consensus guidelines for surgical resection of mucinous neoplasms
      cannot be applied to all cystic lesions of the pancreas.
AB  - BACKGROUND & AIMS: International consensus guidelines, aimed at predicting
      malignancy, are available for surgical resection of mucinous cysts but not for
      other cystic lesions of the pancreas. We sought to determine whether the
      consensus guidelines can be applied to all cystic lesions of the pancreas.
      METHODS: We identified all patients who underwent surgical resection of
      pancreatic cysts from 2001-2007. Pathology analyses of surgical specimens served
      as the reference standard. Surgical resection criteria proposed by the Sendai
      Guidelines and 5 modifications of these criteria were tested to determine their
      accuracy for diagnosis of malignant cysts. RESULTS: Patients with cystic lesions
      of the pancreas (n = 154; mean age, 59.8 years; 64% women) underwent resection
      and met prespecified study criteria. Twenty-one patients had a malignancy. The
      classification cyst size > or = 3 cm had an accuracy of 56%, negative predictive
      value of 84%, and identified only 57% of the malignant cysts. The classification
      cyst size > or = 3 cm or cyst with main pancreatic duct > or = 10 mm had an
      accuracy of 55%, negative predictive value of 86%, and identified 66% of
      malignant cysts. The modified criterion of cyst size > or = 3 cm or cyst with
      main pancreatic duct > 3 mm had an accuracy of 48%, negative predictive value of
      94%, and identified 91% (19/21) of the malignancies. Cyst size (odds ratio, 1.05)
      and pancreatic duct dilation > 3 mm (odds ratio, 10.5) were strong and
      independent predictors of malignancy. CONCLUSIONS: When applied to all cystic
      lesions of the pancreas, the international consensus criteria cause some
      malignant cysts to be missed. Modified criteria could identify most malignant
      cysts, although overall accuracy remains low.

PMID- 19577008
TI  - The impact of narrow band imaging in screening colonoscopy: a randomized
      controlled trial.
AB  - BACKGROUND & AIMS: Narrow band imaging (NBI) is an imaging technique that allows
      a better definition of capillary pattern and improves the contrast between
      adenomas and the surrounding mucosa. Conflicting data exist on the ability of NBI
      to improve detection of colonic neoplasm; the impact of NBI is being tested in
      several screening scenarios. We evaluated whether the routine use of NBI,
      compared with white light (WL), during the withdrawal phase of screening
      colonoscopy improved adenoma detection. METHODS: This randomized controlled study
      included consecutive 50- to 69-year-old patients with positive immunologic fecal
      occult blood tests. They were randomly assigned to groups that were examined with
      WL (n = 108) or NBI (n = 103) during the withdrawal phase of their colonoscopies.
      The primary end point was the adenoma detection rate. The prevalence of non
      polypoid and the total number of adenomas were also evaluated. RESULTS: The
      number of total and mean per-patient adenomas were 201 (1.95 +/- 2.3) and 198
      (1.83 +/- 2.1) in the NBI and WL groups, respectively (P = .69). The adenoma
      detection rates were 57.3% for patients examined by NBI and 58.3% for those
      examined by WL (P = .88). A total of 41 non-polypoid adenomas were identified (26
      in the NBI and 15 in the WL groups, P = .16). The flat adenoma detection rates
      were 21.4% and 9.3% in the NBI and WL groups, respectively (P = .019).
      CONCLUSIONS: The routine use of NBI in screening colonoscopy did not increase the
      adenoma detection rate. NBI seems to improve the detection of flat adenomas,
      although additional studies are necessary.

PMID- 19577009
TI  - A 38-year-old with recurrent colitis. Is it noncompliance?

PMID- 19577007
TI  - Reactivation of hepatitis B with reappearance of hepatitis B surface antigen
      after chemotherapy and immunosuppression.
AB  - BACKGROUND & AIMS: HBV infection may reactivate in the setting of
      immunosuppression, although the frequency and consequences of HBV reactivation
      are not well known. We report 6 patients who experienced loss of serologic
      markers of hepatitis B immunity and reappearance of HBsAg in the serum as a
      result of a variety of acquired immune deficiencies. METHODS: Between 2000 and
      2005, six patients with reactivation of hepatitis B were seen in consultation by
      the Liver Diseases Branch at the Clinical Center, National Institutes of Health.
      The course and outcome of these 6 patients were reviewed. RESULTS: All 6 patients
      developed reappearance of HBsAg and evidence of active liver disease after stem
      cell transplantation (n = 4), immunosuppressive therapy (n = 1), or change in
      human immunodeficiency virus antiretroviral regimen (n = 1), despite having
      antibody to HBsAg (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc)
      without HBsAg before. All 6 patients developed chronic hepatitis B, 2 patients
      transmitted hepatitis B to their spouses, and 1 patient developed cirrhosis. The
      diagnosis of hepatitis B reactivation was frequently missed or delayed and often
      required interruption of the therapy for the underlying condition. None of the
      patients received antiviral prophylaxis against HBV reactivation. CONCLUSIONS:
      Serologic evidence of recovery from hepatitis B infection does not preclude its
      reactivation after immunosuppression. Screening for serologic evidence of
      hepatitis B and prophylaxis of those with positive results by using nucleoside
      analogue antiviral therapy should be provided to individuals in whom
      immunosuppressive therapy is planned.

PMID- 19577010
TI  - A systematic prospective comparison of noninvasive disease activity indices in
      ulcerative colitis.
AB  - BACKGROUND & AIMS: There is no reliable standard of disease activity in
      ulcerative colitis (UC). We performed a prospective study to systematically
      compare all non-invasive disease activity indices in patients with UC and to
      identify cutoff scores that correspond to remission and response. METHODS: The
      study included adults with UC (n = 86; 52% males, mean age 37.6 +/- 13.7 years).
      Items from the following indices were scored: partial Mayo score, Rachmilewitz,
      Lichtiger, Seo, Pediatric Ulcerative Colitis Activity Index (PUCAI), Partial
      Powell-Tuck, Endoscopic-Clinical Correlation, Beattie, and Walmsley. Physician
      and patient global assessments, colonoscopic scores, blood test data, and the
      full Mayo scores were used to assess construct and discriminative validity. A
      follow-up evaluation of 61 patients was used to assess test-retest reliability
      and responsiveness. RESULTS: The Walmsley index and PUCAI were best in assessing
      disease activity, determined by all 4 clinimetric properties. In assessing
      validity, the mean correlation coefficients for the 5 included constructs were r
      = 0.80 and r = 0.79 for the Walmsley and PUCAI, respectively (P < .001 for each).
      The partial Mayo score accurately determined disease activity in 3 of the 4
      clinimetric properties; the Rachmilewitz index accurately assessed patients in 2
      of the properties. Cutoff scores that defined combined clinical-endoscopic
      remission and response were determined using receiver operating characteristic
      curve analyses for all instruments. CONCLUSIONS: The Walmsley index and PUCAI are
      valid, reliable and responsive noninvasive measures to assess disease activity in
      adults with UC. Given their robust clinimetric properties, use of these indices
      might permit less-frequent endoscopic assessment in patients with UC-both in
      research and in clinical practice.

PMID- 19577012
TI  - Performance of five two-sample location tests for skewed distributions with
      unequal variances.
AB  - Tests for comparing the locations of two independent populations are associated
      with different null hypotheses, but results are often interpreted as evidence for
      or against equality of means or medians. We examine the appropriateness of this
      practice by investigating the performance of five frequently used tests: the two
      sample T test, the Welch U test, the Yuen-Welch test, the Wilcoxon-Mann-Whitney
      test, and the Brunner-Munzel test. Under combined violations of normality and
      variance homogeneity, the true significance level and power of the tests depend
      on a complex interplay of several factors. In a wide ranging simulation study, we
      consider scenarios differing in skewness, skewness heterogeneity, variance
      heterogeneity, sample size, and sample size ratio. We find that small differences
      in distribution properties can alter test performance markedly, thus confounding
      the effort to present simple test recommendations. Instead, we provide detailed
      recommendations in Appendix A. The Welch U test is recommended most frequently,
      but cannot be considered an omnibus test for this problem.

PMID- 19577011
TI  - Epidemiology of eosinophilic esophagitis over three decades in Olmsted County,
      Minnesota.
AB  - BACKGROUND & AIMS: Data on secular trends and outcomes of eosinophilic
      esophagitis (EE) are scarce. We performed a population-based study to assess the
      epidemiology and outcomes of EE in Olmsted County, Minnesota, over the last 3
      decades. METHODS: All cases of EE diagnosed between 1976 and 2005 were identified
      using the Rochester Epidemiology Project resources. Esophageal biopsies with any
      evidence of esophagitis and/or eosinophilic infiltration were reviewed by a
      single pathologist. Clinical course (treatment, response, and recurrence) was
      defined using information collected from medical records and prospectively via a
      telephone questionnaire. Incidence rates per 100,000 person years were directly
      adjusted for age and sex to the US 2000 population structure. RESULTS: A total of
      78 patients with EE were identified. The incidence of EE increased significantly
      over the last 3 of the 5-year intervals (from 0.35 [95% confidence interval
      (CI)], 0-0.87] per 100,000 person-years during 1991-1995 to 9.45 [95% CI, 7.13
      11.77] per 100,000 person-years during 2001-2005). The prevalence of EE was 55.0
      (95% CI, 42.7-67.2) per 100,000 persons as of January 1, 2006, in Olmsted County,
      Minnesota. EE was diagnosed more frequently in late summer/fall. The clinical
      course of patients with EE was characterized by recurrent symptoms (observed in
      41% of patients). CONCLUSIONS: The prevalence and incidence of EE is higher than
      previously reported. The incidence of clinically diagnosed EE increased
      significantly over the last 3 decades, in parallel with endoscopy volume.
      Seasonal incidence was greatest in late summer and fall. EE also appears to be a
      recurrent relapsing disease in a substantial proportion of patients.

PMID- 19577013
TI  - Analysis of the phylogenetic relationship of Anopheles species, subgenus Cellia
      (Diptera: Culicidae) and using it to define the relationship of morphologically
      similar species.
AB  - Studies on the relationship of various vectors and non-vectors of malaria from
      the evolutionary point of view are important. Use of molecular methods to define
      phylogeny helps to understand the interrelationship among the members of the
      anophelines and elucidate the ambiguity that has arisen from improper
      classification. It could also help to design molecular markers for species
      differentiation, particularly in those which pose difficulty when classified,
      based on morphological features. In the present study, the phylogenetic
      relationships among the species of the anophelines of subgenus Cellia are
      inferred from the mitochondrial genes COI and COII, the ribosomal RNA gene, in
      particular the D3 region, and Internal Transcribed Spacer 2 (ITS2) region. The
      molecular phylogeny obtained in this work matches with that of the classical
      morphological taxonomy reasonably well, and was useful in properly defining
      species positions and resolving the ambiguity that normally arises due to
      morphological taxonomy. The correct arrangement of the various anopheline taxa as
      per the traditional morphological character-based classification of anophelines
      was there when we considered the D3 region of 28S rRNA gene and ITS2 region of
      rDNA. However, the arrangement of the taxa did not match with that of the
      morphological classification in some aspects, when we considered the COI and COII
      region of mitochondrial DNA. It may have been due to the variable degree of the
      rate of evolution of the different genes within the organism. Thus, a proper
      selection of those particular genes that evolve at the rate that is reflected at
      the species differentiation level, could help to construct the correct
      phylogenetic relationship among the anophelines and could be used to correlate
      with the grouping pattern done from the morphological perspective.

PMID- 19577014
TI  - Physical, structural, and functional properties of the beta1 integrin-like
      fibronectin receptor (beta1EhFNR) in Entamoeba histolytica.
AB  - The presence in Entamoeba histolytica of a fibronectin (FN) receptor, which is
      antigenically related to beta1 integrin-like molecules and shows 99% homology
      with the intermediate subunit-2 of the Gal/GalNAc-specific lectin has been
      described. The E. histolytica genome has been sequenced, and its analysis shows
      no integrin sequences. Here we provide further evidence to demonstrate that this
      molecule behaves as integrin-like in its physical, structural and functional
      properties. The purified beta1EhFNR complex is resolved into three polypeptides
      of 150, 140, and 130 kDa. Transmission electron microscopy showed individual
      complexes consisting of oblong heads of 3 nm x 4 nm and two projecting arms 6-7
      nm in length. In the absence of detergent, these complexes formed aggregates that
      were composed of clusters or "rosettes" of between two and six or more beta1EhFNR
      complexes. The physical properties of the purified beta1EhFNR complexes were:
      R(S)=5.8 nm, S(20)W=8.3, f/f(0)=1.4. This complex was seen in close physical
      association with adhesion plates and phagocytic invaginations, using confocal
      microscopy and the 3C10 mAb that recognizes these three subunits complex.
      Regulation of its surface expression is not dependent on protein synthesis;
      rather it is regulated by inward and outward mobilization of the molecules. The
      presence and antigenic similarity of putative beta1EhFNRs in different strains
      and species of Entamoeba was analyzed using the 3C10 mAb; this mAb recognized the
      complex in all E. histolytica species, however there was no recognition in E.
      dispar, E. invadens, and Laredo strains. Finally, evidence is provided about post
      translational modifications such as tyrosine phosphorylation and glycosylation
      suffered by the beta1EhFNR complex.

PMID- 19577015
TI  - Effect of human immunodeficiency virus type 1 protease inhibitor therapy and
      subtype on development of resistance in subtypes B and G.
AB  - Europe is currently observing a significant rise in non-B subtypes. Consequently,
      the effect of genetic variability on therapy response or genotypic resistance
      interpretation algorithms is an emerging concern. The purpose of this study is to
      investigate the amino acid substitutions selected under drug pressure in the
      protease of human immunodeficiency virus type 1 (HIV-1) subtypes B and G, and
      determine if there are any significant differences. We investigated therapy
      related and subtype-related substitutions in the protease, considering subtype,
      overall protease inhibitor treatment and individual drug exposure. Many mutations
      were significantly related to protease inhibitor (PI) therapy, with mutations
      exclusive to subtype B or subtype G. Some mutations are at positions related to
      resistance in both subtypes, but the amino acid substitution is different. Other
      mutations were significantly associated with subtype and PI selective pressure
      (p<0.05), pointing towards a differential selective pressure in both subtypes. We
      confirmed previous reports on the subtype-dependent selection of D30N and 89I,
      and identified a new mutation with such differential selective pressure: 37D was
      preferentially selected by lopinavir in subtype B. Other novel mutations found
      under therapy pressure were 13A, 35N, K55R, I66F, I72L/T, T74S, 82M and 89I/V.
      Our study indicates that even though in general, drug selective pressure and
      resistance pathways are relatively similar between subtypes B and G, some
      differences do occur, leading to subtype-dependent substitutions.

PMID- 19577016
TI  - Lung volumes and mean apnea duration in obstructive sleep apnea.
AB  - Former studies suggested that lung volumes might play a role in pathomechanisms
      of obstructive sleep apnea (OSA). Mean apnea duration (MAD) is a rarely
      investigated parameter in OSA but is possibly a surrogate of arousal threshold.
      The aim of this study was to evaluate the influence of lung volumes to MAD in
      OSA. In 69 patients with obstructive sleep apnea (51 male und 18 female, BMI
      34.2+/-6.0 kg/m(2), age 53.6+/-9.7 years, AHI 43.1+/-21.1/h) we performed a
      polysomnography and pulmonary function testing in daytime. There was a
      significant correlation between MAD and residual volume (RV) (r=0.51; p<0.001),
      which was the highest correlation we found. In linear regression analysis RV
      remained the only independent variable with significant influence on MAD
      (p<0.001). We could show that RV seems to play a role in the mechanisms of apnea
      termination in terms of MAD. MAD reflects the time until a specific negative
      intrathoracic pressure is reached to induce an arousal. In this process
      dependency on RV could explain our results. Despite some limitations these
      results provide some new aspects in understanding pathophysiology of OSA.

PMID- 19577017
TI  - How microbes tolerate ethanol and butanol.
AB  - New robust biocatalysts are needed to depolymerize or hydrolyze recalcitrant
      heterogeneous lignocellulosic biomass polymers into monomers and to convert the
      mixed substrates into biofuels. The ideal biocatalysts should be able to tolerate
      inhibitory compounds released from biomass hydrolysis and increased
      concentrations of the final products: ethanol or butanol. The solvent tolerance
      trait plays an important role in cost-effective recovery processes. Here we
      provide an overview of the literature of fermenting microbes in response to
      increased ethanol or butanol concentrations, aimed to provide insight on how
      microbes deal with and adapt to the ethanol and butanol stress.

PMID- 19577018
TI  - On "impact of surface type, wheelchair weight, and axle position on wheelchair
      propulsion by novice older adults".
AB  - The mechanical efficiency of propelling manual wheelchairs is a very important
      topic. Wheelchair users, clinicians, manufacturers and payers would all benefit
      from better understanding of mechanical efficiency. However, the measurement of
      the mechanical efficiency is a nontrivial challenge. Cowan et al deserve a lot of
      credit for tackling such a difficult problem in their article "Impact of surface
      type, wheelchair weight, and axle position on wheelchair propulsion by novice
      older adults." The study demonstrated good internal validity in detecting a 4%
      difference in peak propulsion forces in wheelchairs that differed in mass by 9.1
      kg. However, the instrumentation used to measure forces altered both the mass and
      inertia of the wheelchair-occupant system--2 factors that directly affect system
      energy. This approach, therefore, affects external validity, and the results
      cannot be extended to infer differences across wheelchair codes. That said, this
      study adds important information to the body of work into mechanical efficiency
      of wheelchairs. We now have evidence to suggest that addition of 9 kg and an 8 cm
      posterior displacement of axle position adversely affects propulsion biomechanics
      in an elderly cohort. Improved methodology can lead to mechanical efficiency
      measurement of different wheelchair models and different wheelchair options.

PMID- 19577020
TI  - Mild traumatic brain injury and posttraumatic stress disorder and their
      associations with health symptoms.
AB  - OBJECTIVE: To determine the association of various symptoms and psychiatric
      diagnoses with a remote history of mild traumatic brain injury (MTBI) and a
      current diagnosis of posttraumatic stress disorder (PTSD). DESIGN: Cross
      sectional cohort study. SETTING: Nonclinical. PARTICIPANTS: Three groups of
      randomly selected community dwelling male U.S. Army Vietnam-era veterans: healthy
      control (n=3218), those injured in a motor vehicle collision (MVC) but without a
      head injury (MVC injury control; n=548), and those who had an MTBI (n=278).
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence of psychiatric diagnoses,
      physical, cognitive, and emotional symptoms, and course of PTSD across time.
      RESULTS: Logistic regression procedures were used to determine group association
      with symptoms and psychiatric diagnosis after controlling for demographic
      variables, combat intensity, medical disorders, and other current psychiatric
      conditions. MTBI was associated with headaches, memory problems, sleep problems,
      and fainting even after controlling for current psychiatric problems (including
      PTSD), as well as demographic variables, combat intensity, and comorbid medical
      conditions. MTBI also was associated with a current diagnosis of PTSD even
      controlling for other demographic, psychiatric, and medical covariates. MTBI did
      not moderate or mediate the relationship between PTSD and current symptomatology.
      However, MTBI did adversely affect long-term recovery from PTSD (odds ratio=1.59,
      95% CI, 1.07-2.37). PTSD also was associated with physical, cognitive, and
      emotional symptoms, and had a larger effect size than MTBI. CONCLUSIONS: MTBI,
      even in the chronic phase years postinjury, is not a benign condition. It is
      associated with increased rates of headaches, sleep problems, and memory
      difficulties. Furthermore, it can complicate or prolong recovery from preexisting
      or comorbid conditions such as PTSD. Similarly, PTSD is a potent cocontributor to
      physical, cognitive, and emotional symptoms.

PMID- 19577019
TI  - Impact of surface type, wheelchair weight, and axle position on wheelchair
      propulsion by novice older adults.
AB  - OBJECTIVE: To examine the impact of surface type, wheelchair weight, and rear
      axle position on older adult propulsion biomechanics. DESIGN: Crossover trial.
      SETTING: Biomechanics laboratory. PARTICIPANTS: Convenience sample of 53
      ambulatory older adults with minimal wheelchair experience (65-87y); men, n=20;
      women, n=33. INTERVENTION: Participants propelled 4 different wheelchair
      configurations over 4 surfaces: tile, low carpet, high carpet, and an 8% grade
      ramp (surface, chair order randomized). Chair configurations included (1)
      unweighted chair with an anterior axle position, (2) 9.05 kg weighted chair with
      an anterior axle position, (3) unweighted chair with a posterior axle position
      (Delta0.08 m), and (4) 9.05 kg weighted chair with a posterior axle position
      (Delta0.08 m). Weight was added to a titanium folding chair, simulating the
      weight difference between very light and depot wheelchairs. Instrumented wheels
      measured propulsion kinetics. MAIN OUTCOME MEASURES: Average self-selected
      velocity, push frequency, stroke length, peak resultant and tangential force.
      RESULTS: Velocity decreased as surface rolling resistance or chair weight
      increased. Peak resultant and tangential forces increased as chair weight
      increased, as surface resistance increased, and with a posterior axle position.
      The effect of a posterior axle position was greater on high carpet and the ramp.
      The effect of weight was constant, but was more easily observed on high carpet
      and ramp. The effects of axle position and weight were independent of one
      another. CONCLUSION: Increased surface resistance decreases self-selected
      velocity and increases peak forces. Increased weight decreases self-selected
      velocity and increases forces. Anterior axle positions decrease forces, more so
      on high carpet. The effects of weight and axle position are independent. The
      greatest reductions in peak forces occur in lighter chairs with anterior axle
      positions.

PMID- 19577021
TI  - Periodic salbutamol in facioscapulohumeral muscular dystrophy: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects on muscle strength of salbutamol administered
      for 6 months using a periodic regimen in patients presenting with
      facioscapulohumeral muscular dystrophy (FSHD). DESIGN: Placebo-controlled double
      blind randomized study. SETTING: Three clinical centers involved in neuromuscular
      disorders. PARTICIPANTS: Ambulatory patients (N=112), 56 per group, with
      genetically confirmed FSHD, age 18 to 60 years. INTERVENTIONS: Salbutamol
      (sustained released formulation) administered orally at a daily dose of 16 mg
      using a periodic dosage regimen (3 wks on, 1 wk off). MAIN OUTCOME MEASURES:
      Muscle strength was assessed with quantitative muscle testing (QMT), manual
      muscle testing (MMT), and timed motor tests. Patients were evaluated at baseline,
      and 3 and 6 months later. Plasma drug assays were carried out at each visit.
      RESULTS: There was no significant change with periodic use of salbutamol in the
      total composite QMT z-score, MMT score, or timed motor tests. Salbutamol was well
      tolerated. Lack of efficacy did not seem to be related to plasma concentrations,
      which were within the expected range. CONCLUSIONS: Results from this study and
      previous controlled trials preclude at present the use of salbutamol as routine
      treatment for FSHD, even if we cannot exclude improvement from anabolic effects
      with a longer duration of treatment.

PMID- 19577022
TI  - Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate
      neuronal repair: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether repetitive and cumulative exposure to low
      frequency pulsed electromagnetic fields (PEMF) targeting painful feet can reduce
      neuropathic pain (NP), influence sleep in symptomatic diabetic peripheral
      neuropathy (DPN), and influence nerve regeneration. DESIGN: Randomized, double
      blind, placebo-controlled parallel study. SETTING: Sixteen academic and clinical
      sites in 13 states. PARTICIPANTS: Subjects (N=225) with DPN stage II or III were
      randomly assigned to use identical devices generating PEMF or sham (placebo) 2
      h/d to feet for 3 months. INTERVENTIONS: Nerve conduction testing was performed
      serially. MAIN OUTCOME MEASURES: Pain reduction scores using a visual analog
      scale (VAS), the Neuropathy Pain Scale (NPS), and the Patient's Global Impression
      of Change (PGIC). A subset of subjects underwent serial 3-mm punch skin biopsies
      from 3 standard lower limb sites for epidermal nerve fiber density (ENFD)
      quantification. RESULTS: Subjects (N=225) were randomized with a dropout rate of
      13.8%. There was a trend toward reductions in DPN symptoms on the PGIC, favoring
      the PEMF group (44% vs 31%; P=.04). There were no significant differences between
      PEMF and sham groups in the NP intensity on NPS or VAS. Twenty-seven subjects
      completed serial biopsies. Twenty-nine percent of PEMF subjects had an increase
      in distal leg ENFD of at least 0.5 SDs, while none did in the sham group (P=.04).
      Increases in distal thigh ENFD were significantly correlated with decreases in
      pain scores. CONCLUSIONS: PEMF at this dosimetry was noneffective in reducing NP.
      However neurobiological effects on ENFD, PGIC and reduced itching scores suggest
      future studies are indicated with higher dosimetry (3000-5000 G), longer duration
      of exposure, and larger biopsy cohort.

PMID- 19577024
TI  - Prevalence of malingering in patients with chronic pain referred for psychologic
      evaluation in a medico-legal context.
AB  - OBJECTIVE: To provide an empirical estimate of the prevalence of malingered
      disability in patients with chronic pain who have financial incentive to appear
      disabled. DESIGN: Retrospective review of cases. SETTING: A private
      neuropsychologic clinic in a southeastern metropolitan area. PARTICIPANTS:
      Consecutive patients (N=508) referred for psychologic evaluation related to
      chronic pain over a 10-year period (1995-2005). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Prevalence of malingering was examined using 2 published
      clinical diagnostic systems (Malingered Pain-Related Disability and Malingered
      Neurocognitive Dysfunction) as well as statistical estimates based on well
      validated indicators of malingering. RESULTS: The prevalence of malingering in
      patients with chronic pain with financial incentive is between 20% and 50%
      depending on the diagnostic system used and the statistical model's underlying
      assumptions. Some factors associated with the medico-legal context such as the
      jurisdiction of a workers' compensation claim or attorney representation were
      associated with slightly higher malingering rates. CONCLUSIONS: Malingering is
      present in a sizable minority of patients with pain seen for potentially
      compensable injuries. However, not all excess pain-related disability is a result
      of malingering. It is important not to diagnose malingering reflexively on the
      basis of limited or unreliable findings. A diagnosis of malingering should be
      explicitly based on a formal diagnostic system.

PMID- 19577023
TI  - Relationship between diabetes codes that affect Medicare reimbursement (tier
      comorbidities) and outcomes in stroke rehabilitation.
AB  - OBJECTIVES: To examine the extent to which diabetes codes that increase
      reimbursement (tier comorbidities) under the prospective payment system are
      related to length of stay and functional outcomes in stroke rehabilitation.
      DESIGN: Secondary data analysis. SETTING: Inpatient rehabilitation facilities
      (N=864) across the United States. PARTICIPANTS: Patients (N=135,097) who received
      medical rehabilitation for stroke in 2002-2003. INTERVENTION: None. MAIN OUTCOME
      MEASURES: Length of stay, FIM instrument, and discharge setting. Diabetes status
      was assigned to 1 of 3 categories: tier (increases reimbursement), nontier (no
      reimbursement effect), and no diabetes. RESULTS: Mean +/- standard deviation age
      of the sample was 70.4+/-13.4 years, and 31% had diabetes (6% tier, 25% nontier).
      Diabetes status by age demonstrated significant (P<.05) interaction effects,
      which lead to the following age-specific findings. In younger stroke patients
      (60y), tier diabetes was associated with shorter lengths of stay compared with
      both groups, lower FIM discharge scores compared with both groups, and lower odds
      of discharge home relative to the no-diabetes group. In older stroke patients
      (80y), tier diabetes was associated with longer lengths of stay compared with
      both groups and with higher FIM discharge scores compared with the nontier group.
      CONCLUSIONS: The diabetes-related conditions identified as tier comorbidities
      under the prospective payment system are significant predictors of stroke
      rehabilitation outcomes, but these relationships are moderated by patient age.

PMID- 19577025
TI  - A study of bone mineral density in adults with disability.
AB  - OBJECTIVES: To examine prevalence of low bone mineral density (BMD) among adults
      with disability, using World Health Organization diagnostic categories. DESIGN:
      Cross-sectional study. SETTING: National Rehabilitation Hospital, Dublin,
      Ireland. PARTICIPANTS: Patients (N=255; 178 men, 77 women) who were disabled for
      at least 3 months because of acquired brain injury, spinal cord injury, other
      neurologic condition, or lower-limb amputation. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Laboratory investigations including intact parathyroid hormone, 25
      hydroxyvitamin D (25-OHD), and sex hormones; and BMD of lumbar spine and at least
      1 hip, measured by dual-energy x-ray absorptiometry and expressed as T scores and
      z scores. RESULTS: Mean age +/- SD of participants was 48.7+/-15.6 years. Vitamin
      D deficiency, 25-OHD level 50 nmol/L or less, occurred in 154 (62.9%);
      insufficiency, a level between 51 and 72 nmol/L, occurred in 36 (14.7%). Based on
      T scores, 108 participants (42.4%) had osteopenia, and 60 (23.5%) had
      osteoporosis. A z score of -1 or less but more than -2 occurred in 76 (29.8%); a
      further 52 (20.4%) had a z score of -2 or less. On multiple linear regression
      analysis, ambulatory status and duration of disability were independent
      predictors of BMD at neck of femur (beta=.152, P=.007; beta=-.191, P=.001,
      respectively) and total proximal femur (beta=.170, P=.001; beta=-.216, P<.001,
      respectively). CONCLUSIONS: Osteopenia and osteoporosis are very common in adults
      with disability participating in rehabilitation, compared with the general young
      adult population. Duration since onset of disability and mobility status are
      independent predictors of BMD at the hip. Bone health monitoring should form part
      of the long-term follow-up in adults with newly acquired disabilities.

PMID- 19577026
TI  - Mechanical and sensorimotor implications with ankle osteoarthritis.
AB  - OBJECTIVE: To understand the mechanical and sensorimotor adaptations that may
      occur with ankle osteoarthritis (OA). DESIGN: Case-control. SETTING: Biodynamics
      research laboratory. PARTICIPANTS: Subjects with ankle OA (n=8; 4 males, 4
      females) were matched to healthy controls (n=8; 4 males, 4 females).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mechanical joint stability
      was assessed with an instrumented ankle arthrometer. Static balance was measured
      using a force platform during a double-legged stance. Isometric ankle/foot
      complex strength in the sagittal and frontal plane was assessed with a handheld
      dynamometer. Last, subjective level of function was assessed using the foot and
      ankle disability index. RESULTS: There were significant group x side interactions
      for anterior displacement, inversion rotation, eversion rotation, ankle isometric
      strength, and the foot and ankle disability index (P<.05). The affected ankle of
      the OA group demonstrated significantly more mechanical stiffness, more
      impairments in ankle/foot isometric strength, and less subjective level of
      function than the matched controls. Additionally, the ankle OA group exhibited
      significantly more center of pressure displacement, total velocity, and medial
      lateral velocity (P<.05). CONCLUSIONS: These limitations observed in joint
      laxity, postural control, muscle strength, and perceived function provide
      evidence that patients with ankle OA display a number of characteristics that
      affect joint stability and overall function. These identified impairments
      necessitate the need for rehabilitation and exercise programs to be developed to
      help improve joint stability and function in patients with ankle OA.

PMID- 19577027
TI  - Mechanical instability after an acute lateral ankle sprain.
AB  - OBJECTIVE: To examine the natural recovery of mechanical laxity after an ankle
      sprain over an 8-week period. DESIGN: Prospective cohort study. SETTING:
      Biodynamics research laboratory. PARTICIPANTS: Subjects with an acute lateral
      ankle sprain (n=16; 7 men, 9 women; age, 19.5+/-0.7y; mass, 64.6+/-8.1 kg;
      height, 171.9+/-9.6 cm) and healthy controls (n=16; 7 men, 9 women; age, 20.4+/
      1.7y; mass, 76.9+/-11.1 kg; height, 176.5+/-11.1 cm) participated. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Subjects with acute ankle sprains were
      tested 3 days after injury and again 8 weeks later. Anterior and posterior
      displacement (mm) and inversion and eversion rotation ( degrees ) were measured
      with an instrumented arthrometer. For each dependent variable, a 2 x 2 x 2
      repeated-measures multivariate analysis of variance was performed. RESULTS: A
      significant interaction was found between group, time, and side for anterior
      translation (F=4.24, P=.05). There were also significant main effects for group.
      There was significantly more anterior displacement at day 3 (F=19.52, P=.001) and
      at week 8 (F=8.45, P=.010) in the injured group compared with the healthy group.
      There was also significantly more inversion rotation at day 3 (F=2.70, P=.002)
      and at week 8 (F=5.4, P=.033) in the injured group compared with the healthy
      group. CONCLUSIONS: The lack of significant differences in mechanical laxity over
      an 8-week period suggests that natural recovery of laxity takes longer than 8
      weeks. Further research needs to be conducted to examine how long this laxity
      persists and the role ankle rehabilitation plays in mechanical stability
      restoration.

PMID- 19577028
TI  - Analgesic prescribing for musculoskeletal complaints in the ambulatory care
      setting after the introduction and withdrawal of cyclooxygenase-2 inhibitors.
AB  - OBJECTIVE: To evaluate the analgesic prescribing patterns for musculoskeletal
      complaints in a nationally representative sample of ambulatory care visits over a
      dynamic period of pharmaceutical treatments. DESIGN: Sequential cross-sectional
      analysis of complex probabilistic survey data with multivariable logistic
      regression analysis. SETTING: National Ambulatory Medical Care Survey and
      National Hospital Ambulatory Medical Care Survey 1999 to 2005. PARTICIPANTS:
      Visits to ambulatory care physicians in the United States from 1999 to 2005 with
      the reason for visit being a musculoskeletal complaint. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Prescribing of cyclooxygenase-2 (COX-2)
      inhibitors, nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs), opiate
      analgesics, nonnarcotic analgesics, and adjuvant analgesic medications for visits
      related to musculoskeletal complaints. RESULTS: There were 41,804 visits for
      musculoskeletal complaints, representing 789 million visits from 1999 to 2005 in
      the weighted analyses. Prescribing for any nonsteroidal anti-inflammatory drugs
      (NSAIDs) remained relatively stable from 1999 to 2005. It appears that COX-2
      inhibitors were substituted for nsNSAIDs initially. After safety concerns arose
      and select COX-2 inhibitors were withdrawn, there were sharp increases in
      prescribing of nsNSAIDs and nonnarcotic analgesics. Opiate analgesics and
      adjuvant analgesics increased in usage over the study period, although apparently
      not in substitution for NSAIDs. CONCLUSIONS: COX-2 inhibitors may have been
      prescribed as substitutes for nsNSAIDs initially, but nsNSAID prescriptions
      returned to prior levels by 2005 as COX-2 inhibitor prescriptions declined. An
      increase in nonnarcotic analgesic prescribing in 2005 may have been caused by a
      class effect concern for NSAIDs. Prescribing of opiate analgesics and adjuvant
      analgesics increased over the study period, although apparently not in
      substitution for NSAIDs.

PMID- 19577029
TI  - Electromyography of the upper limbs during computer work: a comparison of 2 wrist
      orthoses in healthy adults.
AB  - OBJECTIVE: To examine the effect of wrist orthoses on the electromyography
      activities of the extensor carpi ulnaris, flexor digitorum superficialis, and
      fibers of the upper trapezius muscles during computer work. DESIGN: A randomized,
      3 x 2 factorial design: orthoses (no orthosis, wearing a custom-made orthosis,
      wearing a commercial orthosis) and tasks (typing, using the mouse). SETTING:
      Laboratory for biomechanics and rehabilitation. PARTICIPANTS: Healthy university
      students (N=23), ranging from 18 to 26 years of age. INTERVENTION: Study
      volunteers performed standardized tasks such as typing and using the mouse while
      wearing 1 of 2 types of wrist orthoses or no orthosis. MAIN OUTCOME MEASURES: We
      used surface electromyography and considered 100% maximum voluntary contraction
      to represent the amplitude of electromyographic activity. RESULTS: We observed a
      significant increase in the electromyographic activity of the trapezius (P<.05)
      with the use of orthoses. No significant difference was observed in the
      activities of the flexor digitorum superficialis or extensor carpi ulnaris in
      participants who typed with or without orthoses (P>.05). However, when the
      participants used the mouse, the extensor muscle presented an increase in
      activity with both orthoses, and the same pattern was observed in the flexor
      muscle when the volunteers used the custom-made orthosis. CONCLUSIONS: Wrist
      orthoses affected the muscle activities in the upper limbs of healthy adults who
      were using a computer. Electromyographic activity increased in the trapezius when
      the subjects used either type of orthosis, and the same pattern was observed in
      the extensor carpi ulnaris when the subjects used the mouse. The flexor digitorum
      superficialis presented an increase in activity only when the subjects worked
      with the mouse and used a custom-made splint.

PMID- 19577030
TI  - Effect of acute fatigue of the hip abductors on control of balance in young and
      older women.
AB  - OBJECTIVE: To examine the effects of acute fatigue of the hip abductors on the
      control of balance in young and older women. DESIGN: Pretest-posttest. SETTING:
      University research laboratory. PARTICIPANTS: Healthy young women (n=20; age,
      23.0+/-1.5y; height, 166.52+/-4.5 cm; mass, 65.33+/-10.5 kg) and community
      dwelling older women (n=20; age, 71.65+/-7.2y; height, 162.31+/-3.8 cm; mass,
      71.16+/-11.6 kg) without a fall history. INTERVENTION: Measurements of control of
      single-limb balance before and after fatiguing the hip abductors of the dominant
      leg. MAIN OUTCOME MEASURE: Performance on 3 clinical assessments of control of
      balance: the modified Functional Reach Test in the forward, left, and right
      directions; the Lower-Extremity Reach Test in forward and lateral directions; and
      the Single-Limb Stance Time Test (SLSTT). RESULTS: Although the younger subjects
      showed a significantly greater control of balance than the older women in most
      tests, control of balance after acute fatigue failed to show a significant
      decline in either age group. The only exception to this was the SLSTT in the
      younger women in whom a significant 26% decline was noted (P<.05). CONCLUSIONS:
      Acute fatigue of the hip abductors did not result in a decreased control of
      balance in healthy young or older women without fall history. Despite
      considerable changes in movement strategies used to complete the postfatigue
      tests of balance, quantitative measures of balance did not decrease.

PMID- 19577031
TI  - Reliability of center of pressure measures for assessing the development of
      sitting postural control.
AB  - OBJECTIVES: To determine the reliability of linear and nonlinear tools, including
      intrasession and intersession reliability, when used to analyze the center of
      pressure (COP) time series during the development of infant sitting postural
      control. DESIGN: Longitudinal study. SETTING: University hospital laboratory.
      PARTICIPANTS: Typically developing infants (N=33; mean +/- SD age at entry in the
      study, 152.4+/-17.6d). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Infants were tested twice in 1 week at each of the 4 months of the study. Sitting
      COP data were recorded for 3 trials at each session (2 each month within 1 week).
      The linear COP parameters of root mean square and range of sway for both the
      anterior-posterior and the medial-lateral directions, and the sway path, were
      calculated. The nonlinear parameters of approximate entropy, Lyapunov exponent,
      and correlation dimension for both directions were also calculated. Intrasession
      and intersession reliability was quantified by the intraclass correlation
      coefficient (ICC). RESULTS: The nonlinear tool of approximate entropy presented
      high intrasession and intersession ICC values compared with all other parameters
      evaluated. Generally, intrasession and intersession reliability increased in the
      last 2 months of the data collection and as sitting posture matured. CONCLUSIONS:
      Our results showed that the evaluation of COP data is a reliable method of
      investigating the development of sitting postural control. The present study
      emphasizes the need for establishing COP reliability before using it as a method
      of examining intervention progress directed at improving the sitting postural
      abilities in infants with motor developmental delays.

PMID- 19577032
TI  - Changes in dynamic trunk/head stability and functional reach after hippotherapy.
AB  - OBJECTIVES: To determine if hippotherapy (therapy using a horse) improves
      head/trunk stability and upper extremity (UE) reaching/targeting in children with
      spastic diplegia cerebral palsy (SDCP). DESIGN: Pre-postoperative follow-up with
      a 12-week intervention and 12-week washout period after intervention. SETTING: A
      human performance laboratory with 6 camera video motion capture systems for
      testing. PARTICIPANTS: Eleven children (age 5-13y, average 8y) with SDCP, 8
      children (age 5-13y, average 8y) without disabilities. INTERVENTION: Hippotherapy
      intervention performed at 3 therapeutic horseback riding centers. MAIN OUTCOME
      MEASURES: Video motion capture using surface markers collecting data at 60 Hz, a
      mechanical barrel to challenge trunk and head stability, and functional
      reach/targeting test on static surface. RESULTS: Significant changes with large
      effect sizes in head/trunk stability and reaching/targeting, elapsed time, and
      efficiency (reach/path ratio) after 12 weeks of hippotherapy intervention.
      Changes were retained after a 12-week washout period. CONCLUSIONS: Hippotherapy
      improves trunk/head stability and UE reaching/targeting. These skills form the
      foundation for many functional tasks. Changes are maintained after the
      intervention ceases providing a skill foundation for functional tasks that may
      also enhance occupational performance and participation.

PMID- 19577033
TI  - What's so great about rehabilitation teams? An ethnographic study of
      interprofessional collaboration in a rehabilitation unit.
AB  - OBJECTIVE: To explore team structures, team relationships, and organizational
      culture constituting interprofessional collaboration (IPC) in a particular
      rehabilitation setting; to develop a description of IPC practice that may be
      translated, adapted, and operationalized in other clinical environments. DESIGN:
      An ethnographic study involving: Field observations: 40 hours, over 4 weeks,
      daily activities, 7 interprofessional meetings, 3 care planning meetings, 1
      business meeting, and 3 family meetings; Individual observations: a
      physiotherapist, an occupational therapist, and a social worker individually
      observed for 45 minutes to an hour; and Interviews: 19 participants, 11
      professions, 27 informal, 5 formal interviews. Data analysis consisted of an
      iterative process involving coding field notes for themes by 3 members of the
      research team by qualitative analysis software. SETTING: Single inpatient spinal
      cord rehabilitation care unit in a Canadian urban academic rehabilitation
      hospital. PARTICIPANTS: Purposive convenience sample of core team, more than 40
      professionals: physiatrist, over 21 nurses, 3 physiotherapists, 3 occupational
      therapists, 2 social workers, chaplain, psychologist, therapeutic recreationist,
      program assistant, program manager, pharmacist, advanced practice leader, 6
      students (1 pharmacy, 4 registered nurse, and 1 psychology), and on-site
      community organizations. After university and hospital ethical approvals, all
      staff members were recruited to participate in the study. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Recurrent examples of
      IPC fit 2 dominant themes: team culture (divided into leadership, care
      philosophy, relationships, and the context of practice) and communication
      structures (both formal and informal). CONCLUSIONS: IPC practice in
      rehabilitation care is supported by clinical, cultural, and organizational
      factors. This understanding of daily IPC work may guide initiatives to promote
      IPC in other clinical team settings.

PMID- 19577034
TI  - Factors predicting inpatient rehabilitation length of stay of acute stroke
      patients in Singapore.
AB  - OBJECTIVE: To determine the predictors of hospital length of stay (LOS) of stroke
      patients at the point of admission. DESIGN: A retrospective cohort study.
      SETTING: An acute hospital rehabilitation center in Singapore. PARTICIPANTS:
      Stroke patients (N=491) admitted between March 2005 and December 2006.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Rehabilitation LOS was calculated as
      the total number of rehabilitation days before discharge. We measured the
      functional status of patients by using the Functional Independence Measure (FIM).
      RESULTS: The median LOS was 29 days (mean = 30.8d). Independent clinical and
      sociodemographic characteristics found to significantly predict rehabilitation
      LOS were FIM motor score at admission, the presence of more than 3 comorbid
      conditions at admission, living with nonimmediate relatives before admission, and
      the hospital subsidy status of the patient. In particular, the admission FIM
      motor score explained 43% of the variation in LOS and decreased the LOS by
      approximately 1.1 days for each 1-point increase in score. CONCLUSION: Patients'
      socioeconomic status and family structure was found to influence LOS and should
      be considered in allocating resources and determining treatment need. The extent
      of motor function of patients at admission is an important factor influencing
      rehabilitation LOS and is a useful tool for facilitating rehabilitation resource
      planning for stroke patients.

PMID- 19577035
TI  - A multivariate examination of temporal changes in Berg Balance Scale items for
      patients with ASIA Impairment Scale C and D spinal cord injuries.
AB  - OBJECTIVE: To provide a multivariate examination of the Berg Balance Scale (BBS)
      in patients with spinal cord injury (SCI) as a first step in developing a balance
      tool for the SCI population. DESIGN: Observational cohort. SETTING: The
      NeuroRecovery Network (NRN), a specialized network of treatment centers providing
      standardized, activity-based therapy for patients with SCI. PARTICIPANTS:
      Patients (N=97) with American Spinal Injury Association Impairment Scale C or D
      SCI who were enrolled in the NRN between March 1, 2005, and June 12, 2007.
      INTERVENTIONS: All enrolled patients received 3 to 5 locomotor training sessions
      a week, according to NRN protocol, and were periodically evaluated for progress
      on functional outcome measurements. MAIN OUTCOME MEASURES: Scores on the items of
      the BBS, six-minute walk test distances, ten-meter walk test speeds, and scores
      on the SCI Functional Ambulation Index. Temporal rates of change of the BBS items
      were examined with a principal components and correlation analysis. RESULTS: The
      first principal component accounted for nearly half of the overall variability in
      the BBS, correlated well with rates of change in functional mobility measures,
      and had good stability in its composition as verified by a resampling analysis.
      Further analysis showed that the composition of the first principal component
      varied with the patient's level of recovery. CONCLUSIONS: The BBS captures a
      significant amount of information about balance recovery in persons with SCI and
      may be a good foundation for a balance tool. However, the utility of BBS items
      may be dependent on a patient's level of recovery. A dynamic balance instrument
      for the SCI population may be needed.

PMID- 19577036
TI  - Comparison of single bout effects of bicycle training versus locomotor training
      on paired reflex depression of the soleus H-reflex after motor incomplete spinal
      cord injury.
AB  - OBJECTIVE: To examine paired reflex depression changes post 20-minute bout each
      of 2 training environments: stationary bicycle ergometer training (bicycle
      training) and treadmill with body weight support and manual assistance (locomotor
      training). DESIGN: Pretest-posttest repeated-measures. SETTING: Locomotor
      laboratory. PARTICIPANTS: Motor incomplete SCI (n=12; mean, 44+/-16y); noninjured
      subjects (n=11; mean, 30.8+/-8.3y). INTERVENTION: All subjects received each type
      of training on 2 separate days. MAIN OUTCOME MEASURE: Paired reflex depression at
      different interstimulus intervals (10 s, 1 s, 500 ms, 200 ms, and 100 ms) was
      measured before and after both types of training. RESULTS: (1) Depression was
      significantly less post-SCI compared with noninjured subjects at all
      interstimulus intervals and (2) post-SCI at 100-millisecond interstimulus
      interval: reflex depression significantly increased postbicycle training in all
      SCI subjects and in the chronic and spastic subgroups (P<.05). CONCLUSIONS: Phase
      dependent regulation of reflex excitability, essential to normal locomotion,
      coordinated by pre- and postsynaptic inhibitory processes (convergent action of
      descending and segmental inputs onto spinal circuits) is impaired post-SCI.
      Paired reflex depression provides a quantitative assay of inhibitory processes
      contributing to phase-dependent changes in reflex excitability. Because bicycle
      training normalized reflex depression, we propose that bicycling may have a
      potential role in walking rehabilitation, and future studies should examine the
      long-term effects on subclinical measures of reflex activity and its relationship
      to functional outcomes.

PMID- 19577037
TI  - Reliability of a new classification system for mobility and self-care in spinal
      cord injury rehabilitation: the Spinal Cord Injury-Interventions Classification
      System.
AB  - OBJECTIVE: To investigate the reliability of the Dutch version of the Spinal Cord
      Injury-Interventions Classification System. DESIGN: Descriptive study. SETTING:
      Three Dutch spinal cord injury facilities. PARTICIPANTS: Six physical therapists,
      6 occupational therapists, and 3 sports therapists. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: A 4- or 5-digit code was used to score
      videotaped interventions on 2 occasions in terms of level, category, and type of
      intervention. We examined the percentage of correctly assigned interventions
      (agreement between the researcher and the participants), agreement between the
      first and second measurements (intrarater reliability), and agreement between the
      therapists of the same discipline (interrater reliability). RESULTS: A total of
      252 interventions were assigned. The agreement between the researcher and the
      participants was good: the percentage of correct interventions was high at both
      measurements (91.7% and 94.4%). Intrarater agreement was also good (90.9%). The
      interrater agreement within the physical therapists and the occupational
      therapists was high at both occasions (mean, 92.3% and 87.0%, respectively), but
      lower within the sports therapists (mean, 69.3%). CONCLUSIONS: The study provided
      first evidence for reliability of the classification system. Further research is
      needed to confirm these results and to test the reliability of other language
      versions.

PMID- 19577038
TI  - Age-associated changes in motor unit physiology: observations from the Baltimore
      Longitudinal Study of Aging.
AB  - OBJECTIVE: To examine motor unit characteristics (size and firing rate)
      associated with aging. DESIGN: Cross-sectional, observational. SETTING:
      Community. PARTICIPANTS: Baltimore Longitudinal Study of Aging participants
      (N=102), aged 22.2 to 94.1 years, were studied. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Surface-represented motor unit size and firing rate were
      collected from the vastus medialis during knee extension at 10%, 20%, 30%, and
      50% of each subject's maximum isometric voluntary contraction (MVC). RESULTS: MVC
      declined with older age (P<.0001). Adjusting for differences in MVC, both firing
      rate and motor unit size per newton force generated began to increase in the 6th
      decade of life. Motor unit size increased per newton force to a greater extent
      than firing rate. Those over the age of 75 years also activated significantly
      larger motor units per unit force (P=.04). Relative to force generated, the
      average firing rate began increasing at 57.8+/-3.4 years and between 50.2 and
      56.4 years (+/-4y) for motor unit size. CONCLUSIONS: The size of motor units and
      firing rates used to achieve a given force changes with age, particularly after
      middle age. Whether these changes precede, follow, or occur concurrent to age
      related modifications in muscle structure and contractile properties or
      sarcopenia is not known.

PMID- 19577039
TI  - Right bundle branch block as a screening test for pulmonary embolism in chronic
      spinal cord injury.
AB  - OBJECTIVES: To evaluate right bundle branch block (RBBB) on electrocardiograms
      (ECGs) as a screening tool for the diagnosis of pulmonary embolism (PE) in a
      chronic spinal cord injury (SCI) population and to determine the prevalence of
      PE. DESIGN: Retrospective analysis. SETTING: Boston Veterans Affairs Healthcare
      System. PARTICIPANTS: Consecutive SCI participants (N=112) who were followed at
      this institution until death between 1999 and 2005 at an average age of 71 years,
      a duration of paralysis of 31 years, with a tetraplegic level in 62%, and no
      useful motor function in 84%. INTERVENTION: Not applicable. MAIN OUTCOME
      MEASURES: PE, as a cause of RBBB, was diagnosed by autopsy, a source of
      thromboembolism, imaging, or other ECG signs of PE. Chronic obstructive lung
      disease was diagnosed by pulmonary function tests and myocardial infarction by
      ECG or echocardiogram. RESULTS: Twenty-nine participants (26%) had RBBB (6 with
      incomplete RBBB). Evidence that PE caused RBBB was found in 21 (72%), with 4 (3
      massive) found by autopsy, 4 by the presence of an embolic source, 3 by imaging,
      2 by the intermittent course of RBBB, 1 by abrupt onset of RBBB before death, and
      7 by other ECG signs. RBBB represented chronic obstructive lung disease or
      myocardial infarction in the remaining 8. The onset of RBBB occurred either
      within months of SCI in 5 (1 before SCI) or years after SCI in 24 (6-50y, median
      32y). RBBB was constant in 27 and intermittent in 2. The duration of RBBB ranged
      from 20 minutes to 31 years, median 4 years. CONCLUSIONS: RBBB may be a useful
      initial screening test for PE complicating chronic SCI. PE, often recurrent and
      sometimes fatal, is prevalent in chronic SCI.

PMID- 19577040
TI  - Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses.
AB  - Sporadic cases of recovery from persistent vegetative state (PVS) after
      administration of intrathecal baclofen (ITB) have been reported without giving
      any possible explanation for its paradoxical effect. We summarize our recent
      findings on 5 patients with PVS treated with ITB and make some speculations on
      the mechanisms responsible for the observed clinical improvement. The patients
      developed spasticity and were judged eligible for ITB therapy. Two weeks after
      pump implantation, patients began to show a clinical improvement that, at the end
      of the 6 months' follow-up, was stable in all but 1 patient, ranging from a mere
      increased alertness to a full recovery of consciousness, as revealed by changes
      of the Coma Recovery Scale-Revised (CRS-R) score. Our findings suggest that ITB
      might favor a variable degree of clinical improvement. A proposal for a
      pharmacodynamic explanation of this effect has not been formally put forward. We
      hypothesize 2 possible mechanisms: first, a modulation confined to spinal cord
      segmental activities and to neuronal centripetal outputs reaching the cortex; and
      second, a modulation of sleep-wake cycles that, although present, may be
      dysregulated and interfere with alertness and awareness. Although our research is
      confined to a few subjects, it provides follow-up information by means of the CRS
      R that is a validated standardized neurobehavioral instrument expressly designed
      for use in patients with PVS. Our observations indicate that further systematic
      investigation of the mechanisms and the putative clinical applications of ITB
      should be undertaken.

PMID- 19577041
TI  - Handling stairs in the seated position for people with unilateral lower-limb
      amputations.
AB  - Handling stairs in the seated position for people with unilateral lower-limb
      amputations. The objective of this uncontrolled pilot study was to test the
      hypotheses that the seated stair-handling method enables people with unilateral
      lower-limb amputations to ascend and descend stairs effectively and safely, and
      with an acceptable level of perceived exertion. Eight people with unilateral
      lower-limb amputations each received a single 20-minute education session on
      climbing stairs in the seated position. The main outcome measures, assessed 3
      days after training, were success in ascending and descending a flight of 11
      stairs, safety, and rating of perceived exertion (Borg CR-10 scale, range 0-10).
      Before training, 3 participants (37.5%) were successful in using a variety of
      methods. After training, all 8 (100%) were successful, but only 7 (87.5%) were
      successful when required to use the seated stair-handling method. Two
      participants had difficulty with this method, one as a result of arm weakness and
      the other as a result of aggravation of knee pain. There were no adverse events.
      Ratings of perceived exertion for the seated method (n=7) ranged from 3 to 7.5
      for stair ascent and 1 to 5.5 for descent. The seated stair-handling method is a
      generally effective, safe, and well-tolerated method for people with unilateral
      lower-limb amputations to ascend and descend stairs.

PMID- 19577042
TI  - Where's the fun in that? Broadening the focus on reward function in depression.

PMID- 19577043
TI  - The JTCVS: a year in review.

PMID- 19577045
TI  - Surgery for adults with congenital heart disease should be performed by
      congenital heart surgeons.

PMID- 19577046
TI  - Uric acid levels and outcomes from coronary artery bypass grafting: is it the
      chicken or the egg?

PMID- 19577047
TI  - Man and machine: understanding the complex physiologic interactions to reduce
      complications.

PMID- 19577048
TI  - Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung
      cancer.
AB  - BACKGROUND: The optimal surgical technique for lobectomy in lung cancer is not
      well defined. Proponents of video-assisted thoracic surgery (VATS) hypothesize
      that less trauma leads to quicker recovery, whereas those who advocate
      thoracotomy claim it as an oncologically superior procedure. However, a well
      balanced comparison of the two procedures is lacking in the literature. METHODS:
      All patients who underwent lobectomy for clinical stage 1A lung cancer by
      computed tomographic and positron emission tomographic scan were identified from
      a prospective database. Patient characteristics were compared by the Student t
      test, Pearson chi(2), and Fisher exact test. A propensity score-matched analysis
      was performed. Survival was assessed by Kaplan-Meier and Cox proportional hazards
      analysis. Complications were assessed by a multivariate logistic regression model
      evaluating age, sex, comorbidities, pulmonary function, tumor size, nodal status,
      surgeon, and histologic characteristics. RESULTS: From May 2002 to August 2007,
      398 patients underwent an attempt at VATS lobectomy and 343 underwent
      thoracotomy. An "intent-to-treat" analysis was performed. There was 1
      postoperative death in each group. Survival by Cox model was no different for
      VATS versus thoracotomy (hazard ratio 0.72; P = .12), whereas age (hazard ratio
      1.03; P < .001), larger tumor size (hazard ratio 1.34; P < .001), and higher
      nodal stage (hazard ratio 1.92; P < .001) were associated with worse survival.
      Logistic regression demonstrated fewer complications for VATS lobectomy (odds
      ratio 0.73; P = .06), whereas age (odds ratio 1.04; P < .001) and tumor size
      (odds ratio 1.2; P < .020) correlated with a greater number of complications.
      Patients undergoing VATS lobectomy demonstrated a 2-day shorter length of stay
      than patients undergoing thoracotomy (P < .001). Propensity score-matched
      analysis supported these findings. CONCLUSIONS: VATS lobectomy and thoracotomy
      demonstrated similar 5-year survivals. However, VATS lobectomy was associated
      with fewer complications and shorter length of hospital stay.

PMID- 19577049
TI  - Solitary fibrous tumors of the pleura: results of surgical treatment and long
      term prognosis.
AB  - OBJECTIVE: We sought to define the long-term outcome of surgically treated
      solitary fibrous tumors of the pleura. METHODS: We performed a retrospective
      review from December 1972 through December 2002. RESULTS: There were 84 patients
      (39 men and 45 women) with a median age of 57 years (range, 34-83 years). Forty
      six patients were symptomatic. Surgical resection included pulmonary wedge
      excision in 62 patients, lobectomy in 4 patients, segmentectomy in 2 patients,
      chest wall resection in 3 patients, isolated pleural resection in 7 patients, and
      chest wall resection with pulmonary wedge excision, lobectomy, or pneumonectomy
      in 3, 2, and 1 patients, respectively. Tumors were polypoid in 57 patients,
      sessile in 20 patients, and intrapulmonary in 7 patients. Histopathology was
      benign in 73 and malignant in 11 patients. Nine (82%) patient with malignant
      tumors and 37 (54%) patients with benign tumors were symptomatic (P = .11). The
      median tumor diameters for malignant and benign tumors were 12.0 and 4.5 cm,
      respectively (P = .001). Operative mortality and morbidity occurred in 3 (3.6%)
      and 7 (8.1%) patients, respectively. Median follow-up in survivors was 146 months
      (range, 23-387 months). Median survival for patients with benign and malignant
      tumors was 284 and 55 months, respectively, and 5-year survival was 88.9% and
      45.5%, respectively (P = .0005). Eight (9.5%) patients had recurrent solitary
      fibrous tumors of the pleura. Recurrences were malignant in 6 and benign in 2
      patients. Localized chest recurrences occurred in 3 patients, all of whom had
      reresection, with 2 patients again having recurrence. CONCLUSION: Resection of
      benign solitary fibrous tumors of the pleura carries an excellent prognosis.
      Larger tumors are more likely to be malignant. Both benign and malignant tumors
      can recur. Although prolonged survival after resection of malignant tumors is
      possible, recurrence is common.

PMID- 19577051
TI  - Comparison of patterns of relapse in thymic carcinoma and thymoma.
AB  - OBJECTIVE: Thymic carcinomas are considered to be more aggressive than thymomas
      and carry a worse prognosis. We reviewed our recent experience with the surgical
      management of thymic tumors and compared the outcomes and patterns of relapse
      between patients with thymic carcinoma and those with thymoma. METHODS: We
      performed a single-institution retrospective cohort study. Data included patient
      demographics, stage, treatment, pathologic findings, and postoperative outcomes.
      RESULTS: During the period 1995-2006, 120 patients with thymic tumors underwent
      surgical intervention, including 23 patients with thymic carcinoma and 97
      patients with thymoma, as classified according to the World Health Organization
      2004 histologic classification. The overall 5-year survival was significantly
      different between patients with thymic carcinoma and those with thymoma (thymic
      carcinoma, 53%; thymoma, 89%; P = .01). Data on relapse were available for 112
      patients. The progression-free 5-year survival was also significantly different
      between patients with thymic carcinoma and those with thymoma (thymic carcinoma,
      36%; thymoma, 75%; P < .01). Using multivariate analysis, thymic carcinoma and
      incomplete resection were found to be independent predictors of progression-free
      survival. Relapses in patients with thymic carcinoma tended to occur earlier, and
      occurred significantly more frequently at distant sites than in patients with
      thymoma (60% vs 13%, P = .01). CONCLUSIONS: Patterns of relapse differ
      significantly between patients with thymic carcinoma and those with thymoma, with
      lower progression-free survival, earlier onset, and more distant relapses in
      patients with thymic carcinoma. Given the greater propensity for distant
      failures, the inclusion of systemic therapy in the treatment of thymic carcinoma
      might take on greater importance. Despite significantly higher rates of distant
      relapse, good overall survival in patients with thymic carcinoma can be achieved.

PMID- 19577053
TI  - Composite cervical skin and cartilage flap provides a novel large airway
      substitute after long-segment tracheal resection.
AB  - OBJECTIVE: Airway replacement after long-segment tracheal resection for benign
      and malignant disease remains a challenging problem because of the lack of a
      substitute conduit. Ideally, an airway substitute should be well vascularized,
      rigid, and autologous to avoid infections, airway stenosis, and the need for
      immunosuppression. We report the development of an autologous tracheal substitute
      for long-segment tracheal resection that satisfies these criteria and
      demonstrates excellent short-term functional results in a large-animal study.
      METHODS: Twelve adult pigs underwent long-segment (6 cm, 60% of total length)
      tracheal resection. Autologous costal cartilage strips measuring 6 cm x 2 mm were
      harvested from the chest wall and inserted at regular 0.5-cm intervals between
      dermal layers of a cervical skin flap. The neotrachea was then scaffolded by
      rotating the composite cartilage skin flap around a silicone stent measuring 6 cm
      in length and 1.4 cm in diameter. The neotrachea replaced the long segment of
      tracheal resection, and the donor flap site was closed with a double-Z plasty.
      Animals were killed at 1 week (group I, n = 4), 2 weeks (group II, n = 4), and 5
      weeks (group III, n = 4). In group III the stent was removed 1 week before death.
      Viability of the neotrachea was monitored by means of daily flexible bronchoscopy
      and histologic examination at autopsy. Long-term morbidity and mortality were
      determined by monitoring weight gain, respiratory distress, and survival.
      RESULTS: There was no mortality during the study period. Weight gain was
      appropriate in all animals. Daily bronchoscopy and postmortem histologic
      evaluation confirmed excellent viability of the neotrachea. There was no evidence
      of suture-line dehiscence. Five animals had distal granulomas that were removed
      by using rigid bronchoscopy. In group III 1 animal had tracheomalacia, which was
      successfully managed by means of insertion of a silicon stent. CONCLUSION: Airway
      reconstruction with autologous cervical skin flaps scaffolded with costal
      cartilages is a novel approach to replace long segments of resected trachea. This
      preliminary study demonstrates excellent respiratory function and survival in
      large animals undergoing resection of more than 50% of their native trachea. Use
      of cervical skin flaps buttressed with costal cartilage is a promising solution
      for long-segment tracheal replacement.

PMID- 19577054
TI  - Recurrent intrathoracic thymomas: potential prognostic importance of cell-cycle
      protein expression.
AB  - OBJECTIVE: Recurrent intrathoracic thymomas may have an unpredictable behavior.
      Cell-cycle protein expression has proven useful in predicting outcome in a
      variety of neoplasms. We investigated its potential prognostic importance in
      recurrent intrathoracic thymomas. METHODS: We reviewed the case histories of 25
      consecutive patients operated on between 1987 and 2004 for intrathoracic
      recurrence (7 mediastinal, 18 nonmediastinal) after radical thymomectomy.
      Complete resection was performed in 14 patients. In the other 11 patients
      incomplete resection was followed by chemotherapy and radiotherapy. Expression of
      cell-cycle proteins (p53, p21, and p27) was assessed by immunohistochemistry in
      specimens retrieved from both initial and recurrent thymomas. Univariate and
      multivariate analysis for prognostic factors present at the time of the
      recurrence was performed. RESULTS: Eight of 14 patients who underwent complete
      resection had a second recurrence after a mean free interval of 20 +/- 9 months,
      and a new complete resection was reperformed in 4. After incomplete resection,
      chemotherapy and radiotherapy allowed total remission in 4 subjects and only 1 of
      these had a second recurrence. Survival after surgery of the recurrence was
      negatively influenced by incomplete recurrence resection (P = .03), first disease
      free interval less than 24 months (P = .03), high p53 (P = .04), low p21 (P =
      .02), low p27 (P = .003) expressions, and combination of these proteins (p53
      high, p21 low, p27 low expression) (P = .0001). Multivariate analysis selected
      the triple combination of cell-cycle protein expression as the most significant
      prognostic variable (P = .02, odds ratio = 11.96, 95% confidence interval = 1.39
      102.63). CONCLUSIONS: Cell-cycle protein expression, and namely the combination
      of high p53, low p21, and low p27 expression, may have a potential prognostic
      importance in recurrent intrathoracic thymomas.

PMID- 19577055
TI  - Hybrid endovascular aortic arch repair using branched endoprosthesis: the second
      generation "branched" open stent-grafting technique.
AB  - OBJECTIVE: We advanced the open stent-grafting technique with a branched
      endoprosthesis, which reconstructs simultaneously the cervical branches and
      descending aorta within an acceptably short interval of deep hypothermic
      circulatory arrest. In this study, we evaluated the efficacy of this new
      technique and assessed the early and midterm results. METHODS: From January 2004
      to September 2007, the branched open stent-grafting technique was performed in 69
      cases (55 men, average age 66.2 years, 36 degenerative aneurysms and 33 aortic
      dissections, 13 [18.8%] in emergency, 7 [10.1%] redo cases). Under deep
      hypothermic circulatory arrest, the branched endoprosthesis was delivered through
      the opened proximal aortic arch, and total arch repair was completed. To avoid
      cerebral embolism, retrograde cerebral perfusion was performed at the end of deep
      hypothermic circulatory arrest. RESULTS: Average time of operation,
      cardiopulmonary bypass, and deep hypothermic circulatory arrest was 417, 130, and
      36 minutes, respectively. A total of 124 cervical stent grafts were inserted and
      successfully delivered in 121 (97.6%). Operative mortality within 30 days was 3
      (4.3%). The major postoperative complications involved 4 (5.8%) strokes and 2
      (2.9%) spinal cord injuries. No aorta-related death was observed after discharge
      from hospital, and the survival was 90.9%, 88.8%, and 88.8% at 1, 2, and 3 years,
      respectively. Six (5.0%) cervical stent grafts showed endoleak; however, all
      these cases were successfully treated by additional endovascular repair.
      CONCLUSION: Aortic arch repair with branched open stent grafting is an effective
      technique with satisfactory early results. In midterm analysis, cervical branch
      events were acceptably rare and controllable. This technique could be an
      attractive alternative to conventional total arch replacement.

PMID- 19577057
TI  - Intraoperative bypass graft flow in intra-aortic balloon pump-supported patients:
      differences in arterial and venous sequential conduits.
AB  - BACKGROUND: The intra-aortic balloon pump is used worldwide as an anti-ischemic
      strategy. However, little is known about the modifications of the graft flowmetry
      during use of intra-aortic balloon pump. METHODS: An observational study aimed at
      analyzing transit-time flow measurements during 1:1 intra-aortic balloon pump use
      and during its cessation in 138 consecutive patients using intra-aortic balloon
      pump before coronary artery bypass grafting (n = 442 graft segments) was
      reported. RESULTS: In normally functioning grafts, the mean diastolic and mean
      blood flow improved significantly during 1:1 intra-aortic balloon pump use
      compared with during intra-aortic balloon pump cessation (P < .001), although
      mean and diastolic arterial pressures were significantly lower (P = .001).
      Arterial and sequential saphenous vein grafts showed greater improvements in mean
      diastolic and mean flow compared with single venous grafts. Surplus graft flow
      (defined as mean flow during 1:1 intra-aortic balloon pump use/mean flow with
      intra-aortic balloon pump off) was recorded (surplus graft flow > 1) during 1:1
      intra-aortic balloon pump use in all normally functioning grafts, with higher
      values in single arterial or sequential saphenous vein grafts versus single
      venous grafts (both P < .001). In the 9 cases of graft failure, the mean
      diastolic, mean systolic, and mean flow were significantly lower and the
      pulsatility index greater, compared with normally functioning grafts (all P <or=
      .001). Blood flow did not change appreciably during 1:1 intra-aortic balloon pump
      use in failed bypass grafts; thus the surplus graft flow approached 1.
      CONCLUSION: In this analysis, use of intra-aortic balloon pump was associated
      with improved diastolic and mean blood flow in bypass grafts. Arterial and
      sequential grafts were associated with greater improvements in blood flow and
      surplus graft flow. Graft failure was associated with poor transit-time flow
      results, high pulsatility index values, and absent surplus graft flow.

PMID- 19577058
TI  - Myocardial viability and cardiac dyssynchrony as strong predictors of
      perioperative mortality in high-risk patients with ischemic cardiomyopathy having
      coronary artery bypass surgery.
AB  - OBJECTIVE: Myocardial viability and left ventricular dyssynchrony are important
      predictors of long-term outcomes in patients with ischemic left ventricular
      dysfunction. The objective of this study was to test the hypothesis that
      assessment of myocardial viability and left ventricular dyssynchrony will predict
      perioperative mortality in high-risk patients with ischemic left ventricular
      dysfunction having coronary artery bypass surgery. METHODS: The study consisted
      of 79 consecutive patients with ischemic cardiomyopathy (age 65 +/- 9 years; 81%
      men; ejection fraction 30% +/- 6%) and logistic European system for cardiac
      operative risk evaluation > 10% having coronary artery bypass surgery. Myocardial
      viability was assessed by delayed contrast-enhanced magnetic resonance imaging.
      Left ventricular dyssynchrony was calculated using tissue Doppler from
      measurements of regional electromechanical coupling times in left ventricular
      basal segments before coronary artery bypass surgery. RESULTS: Twenty (25.3%)
      patients died within 30 days following coronary artery bypass surgery. Survivors
      (n = 59) showed a larger extent of viable myocardium (6.9 +/- 3.6 viable segments
      vs 3.4 +/- 3.3 viable segments, P < .001) and smaller left ventricular
      dyssynchrony (75 +/- 5 ms vs 179 +/- 83 ms, P < .001) than nonsurvivors. The
      presence of significant dyssynchrony (>or=105 ms) and absence of myocardial
      viability (<5 viable segments) independently predicted 30-day mortality with
      hazard ratio 3.26, 95% confidence interval 1.61 to 8.33 (P < .01) and hazard
      ratio 1.72, 95% confidence interval 1.59 to 1.89 (P < .01), respectively. All but
      2 patients (94.1%) with viable myocardium and without left ventricular
      dyssynchrony survived coronary artery bypass surgery as compared with only 12
      (52.2%) patients with nonviable myocardium and severe dyssynchrony (P < .001).
      CONCLUSIONS: In high-risk patients with ischemic left ventricular dysfunction
      having coronary artery bypass surgery, both myocardial viability and left
      ventricular dyssynchrony are important predictors of perioperative outcome.
      Assessment of myocardial viability and left ventricular dyssynchrony should be a
      routine part of the preoperative evaluation of these patients.

PMID- 19577059
TI  - Outcomes of double valve surgery for active infective endocarditis.
AB  - OBJECTIVE: In active infective endocarditis the need for operating simultaneously
      on the aortic and mitral valves is frequent. There are no studies in the
      literature documenting long-term outcomes of double valve surgery for active
      endocarditis. METHODS: Ninety patients underwent double valve surgery for active
      endocarditis over a 26-year period (mean age, 53 +/- 16 years; 71% male
      patients). Prosthetic endocarditis was seen in 32 patients. Staphylococcus
      species was isolated in 29%. Forty-six (51%) patients had abscesses. Surgical
      intervention consisted of valve repair or replacement with limited infection or
      radical resection, patch reconstruction, and valve replacement for abscesses.
      Mean follow-up was 5.9 +/- 4.7 years (range, 0-18 years) and was complete.
      RESULTS: There were 14 (15.6%) in-hospital deaths and 29 (32.2%) late deaths.
      Overall survival at 5, 7, and 10 years was 68% +/- 5%, 59% +/- 6%, and 49% +/-
      6%, respectively, and was reduced in those undergoing operations for prosthetic
      compared with native endocarditis (7-year survival, 39% +/- 9% vs 71% +/- 7%; P <
      .001). Freedom from recurrent endocarditis was 84% +/- 5% at 10 years. Freedom
      from reoperation was 91% +/- 4% at 10 years. Event-free survival at 7 and 10
      years was 60% +/- 6% and 47% +/- 7%, respectively. No difference was observed
      between the native and prosthetic groups for recurrent endocarditis, late
      reoperation, or event-free survival. Prosthetic endocarditis, increasing age,
      preoperative shock, and diabetes mellitus were independent predictors of death
      from all causes. CONCLUSIONS: Double valve surgery for active endocarditis
      remains technically challenging and associated with significant morbidity and
      mortality perioperatively and in the longer term. Outcomes are worse in those who
      have prosthetic valve endocarditis.

PMID- 19577060
TI  - Comparison of radial artery patency according to proximal anastomosis site:
      direct aorta to radial artery anastomosis is superior to radial artery composite
      grafting.
AB  - OBJECTIVE: The radial artery is frequently the second graft of choice after the
      left internal thoracic artery in coronary artery bypass graft surgery. However,
      the optimal radial artery proximal anastomosis site remains controversial. The
      aim of the present study was to compare the radial artery patency according to
      its use as either an aorta-radial artery graft or composite radial artery graft
      in coronary artery bypass grafting. METHODS: A total of 1735 patients received
      coronary artery bypass grafting using the radial artery between January 2001 and
      July 2007, of whom 893 received serial computed tomographic coronary
      angiographies; these patients formed the basis of the current study. The patients
      were divided into 2 groups: group I (direct radial artery to aortic anastomosis,
      n = 451 patients) and group II (radial artery composite grafting with the left
      internal thoracic artery, n = 442 patients). The number of distal radial artery
      anastomoses performed in group I was 657 and 749 in group II. Sequential
      bypassing was performed in 399 patients. RESULTS: The early patency rate was
      significantly higher in group I than in group II (98.3% vs 94.5%; P = .004). The
      1-, 2-, and 5-year patency rates were also higher in group I than in group II
      (93.8% +/- 1.2%, 90.5% +/- 1.6%, and 74.3% +/- 6.1%, vs 90.5% +/- 1.4%, 85.3% +/-
      1.9%, and 65.2% +/- 4.2%, respectively; P = .004). Multivariate analysis showed
      composite grafting (P = .02), the degree of target vessel stenosis <90% (P =
      .001), and the target revascularization site (P = .005) to be significant risk
      factors for occlusion. CONCLUSION: The results of the current data showed
      superior early and late patency rates of coronary artery bypass grafting with
      radial artery to aorta anastomosis compared with left internal thoracic artery
      radial artery composite grafting.

PMID- 19577061
TI  - Effective transcatheter valve implantation after pulmonary homograft failure: a
      new perspective on the Ross operation.
AB  - OBJECTIVE: The Ross procedure offers good autograft function and low reoperation
      rates for the neoaortic valve; however, the rate of conduit dysfunction in the
      right ventricular outflow tract remains a concern. This study assessed
      percutaneous pulmonary valve implantation in this setting. METHODS: We
      retrospectively analyzed outcomes of 12 patients (mean age 28 +/- 5 years)
      referred for percutaneous pulmonary valve implantation to treat right ventricle
      pulmonary artery conduit failure 11.1 +/- 3.3 years after Ross procedure.
      RESULTS: Percutaneous pulmonary valve implantation was feasible in all 12
      patients, with no procedural complications (procedure time 99 +/- 16 minutes,
      fluoroscopy time 21 +/- 6 minutes). Right ventricular outflow tract gradient
      during catheterization and pulmonary regurgitant fraction on magnetic resonance
      imaging fell after valve implantation (gradient 34 +/- 6 to 14 +/- 3 mm Hg, P <
      .01, regurgitant fraction 20% +/- 6% to 2% +/- 1%, P < .05). After restoration of
      right ventricular outflow tract function, indexed right ventricular end-diastolic
      volume decreased (91 +/- 13 to 78 +/- 12 mL x beat(-1) x m(-2), P < .01) and
      maximal cardiopulmonary exercise performance improved (peak oxygen consumption
      25.4 +/- 2.3 to 30.8 +/- 3.0 mL x kg(-1) x min(-1), P < .01). During follow-up
      (18.8 +/- 4.6 months), there was 1 device explantation (restenosis). The
      probabilities of freedom from right ventricular outflow tract reoperation were
      100% at 1 year and 90% at 3 years. CONCLUSIONS: Percutaneous pulmonary valve
      implantation provides an effective transcatheter treatment strategy to prolong
      the lifespan of right ventricle-pulmonary artery conduits after the Ross
      procedure, reducing the reoperation burden on patients with aortic valve disease.

PMID- 19577062
TI  - Clinical outcome 5 to 18 years after the Fontan operation performed on children
      younger than 5 years.
AB  - OBJECTIVE: This study assessed clinical condition at midterm follow-up after
      total cavopulmonary connection for a functionally univentricular heart performed
      on children younger than 5 years. METHODS: Thirty-four Fontan patients (median
      age 10.4 years, range 6.8-20.7 years, 22 boys, median follow-up 7.8 years, 5.0
      17.8 years) underwent electrocardiography, Holter monitoring, bicycle exercise
      testing, cardiac magnetic resonance imaging, and N-terminal prohormone brain
      natriuretic peptide (NT-pro-BNP) analysis. RESULTS: Twenty-three patients (68%)
      were in sinus rhythm. Holter monitoring demonstrated normal mean heart rate, low
      maximal heart rate, and no clinically significant arrhythmias or sinus node
      dysfunction. With maximal bicycle ergometry (n = 19), maximum workload (60% of
      normal), maximum heart rate (90% of normal), and maximal oxygen uptake (69% of
      normal) were all significantly lower in the Fontan group than in a control group
      (P < .001). Variables of submaximal exercise indicated less efficient oxygen
      uptake during exercise in all Fontan patients. Ejection fraction was lower than
      in control subjects (59% +/- 13% vs 69% +/- 5%, P < .001). Mean end-diastolic and
      end-systolic volumes and ventricular mass were higher than in control subjects (P
      < .001). Mean NT-pro-BNP levels were increased relative to reference values, but
      only 8 patients had levels above the upper reference limit. CONCLUSION: At
      midterm follow-up, Fontan patients were in acceptable clinical condition, with
      preserved global ventricular function, moderately decreased exercise capacity,
      and NT-pro-BNP levels within reference range. Systemic ventricular mass was
      elevated, however, suggesting contractility-afterload mismatch. Long-term
      consequences for ventricular function merit further investigation.

PMID- 19577063
TI  - Blood flow distribution in a large series of patients having the Fontan
      operation: a cardiac magnetic resonance velocity mapping study.
AB  - OBJECTIVES: Our goal was to determine flow distribution in the cavopulmonary
      connections of patients with and without bilateral superior venae cavae who had
      the Fontan procedure. No large series exists that establishes the flow
      distributions in Fontan patients, which would be an important resource for
      everyday clinical use and may affect future surgical reconstruction. METHODS: We
      studied 105 Fontan patients (aged 2-24 years) with through-plane phase contrast
      velocity mapping to determine flow rates in the inferior and superior venae cavae
      and left and right pulmonary arteries. Superior caval anastomosis type included
      40 bidirectional Glenn shunts (of which 15 were bilateral) and 53 hemi-Fontan
      anastomoses; Fontan type included 69 intra-atrial baffles, 28 extracardiac
      conduits, and 4 atriopulmonary connections. RESULTS: Total caval flow was 2.9 +/-
      1.0 L x min(-1) x m(-2), with an inferior vena cava contribution of 59% +/- 15%.
      Total pulmonary flow was 2.5 +/- 0.8 L x min(-1) x m(-2), statistically less than
      caval flow and not explained by fenestration presence. The right pulmonary artery
      contribution (55% +/- 13%) was statistically greater than the left. In patients
      with bilateral superior cavae, the right cava accounted for 52% +/- 14% of the
      flow, with no difference in pulmonary flow splits (50% +/- 16% to the right). Age
      and body surface area correlated with percent inferior caval contribution (r =
      0.60 and 0.74, respectively). Superior vena cava anastomosis and Fontan type did
      not significantly affect pulmonary flow splits. CONCLUSIONS: Total Fontan cardiac
      index was 2.9 L x min(-1) x m(-2), with normal pulmonary flow splits (55% to the
      right lung). Inferior vena caval contribution to total flow increases with body
      surface area and age, consistent with data from healthy children.

PMID- 19577064
TI  - Risk factors for early pulmonary valve replacement after valve disruption in
      congenital pulmonary stenosis and tetralogy of Fallot.
AB  - OBJECTIVE: Congenital heart defects with a component of pulmonary stenosis are
      often palliated in childhood by disrupting the pulmonary valve, either by means
      of dilation or excision. It is unclear what factors affect a patient's ability to
      tolerate long-term pulmonary insufficiency before requiring pulmonary valve
      replacement. We analyze potential factors that are related to the interval
      between pulmonary valve disruption and pulmonary valve replacement. METHODS: One
      hundred seven patients were analyzed. They had a congenital diagnosis of
      pulmonary stenosis or tetralogy of Fallot, had their first pulmonary valve
      replacement between 2002 and 2008, and had a known interval between pulmonary
      valve disruption and pulmonary valve replacement. The median age at the time of
      surgical intervention was 2 years for pulmonary valve disruption (range, 0-56
      years) and 26 years for pulmonary valve replacement (range, 1-72 years). The
      median interval was 23 years (range, 0-51 years). Potential related factors were
      sex, race, initial diagnosis and procedure, age at pulmonary valve disruption,
      prior shunt operation, presence of branch pulmonary artery stenosis, and degree
      of pulmonary regurgitation. RESULTS: As determined by using univariate analysis,
      male patients had a shorter interval than female patients (median, 16 vs 26
      years; P = .01), and African American patients had a shorter interval than white
      patients (median, 16 vs 25 years; P = .049). A significant correlation was also
      identified between age at the time of pulmonary valve disruption and the
      subsequent interval to pulmonary valve replacement. Overall, the interval tended
      to increase as age at disruption increased (P < .0001). Although the presence of
      branch pulmonary artery stenosis determined by the need for concomitant pulmonary
      arterioplasty was associated with a significantly shorter interval to pulmonary
      valve replacement (21 vs 24 years, P = .02), stenosis determined based on small
      branch pulmonary artery diameter was correlated to a prolonged interval to
      pulmonary valve replacement (P = .009). Initial diagnosis, prior palliative shunt
      operation, and degree of pulmonary regurgitation had no effect on the interval
      between pulmonary valve disruption and subsequent pulmonary valve replacement. As
      determined by using multivariate analysis, only male sex and small pulmonary
      artery diameter remained significant factors. CONCLUSIONS: Male sex appears to
      shorten the interval between pulmonary valve disruption and pulmonary valve
      replacement, whereas small branch pulmonary artery diameter appears to lengthen
      the interval. Knowing which factors are detrimental and which are protective
      might help identify patients who are prone to a more rapid progression of right
      heart failure from free pulmonary insufficiency, possibly steering them toward
      more frequent follow-up or more aggressive heart failure medical regimens.

PMID- 19577065
TI  - Minimally invasive surgical ablation of atrial fibrillation: six-month results.
AB  - BACKGROUND: A minimally invasive surgery for treatment of atrial fibrillation was
      developed with bilateral pulmonary vein isolation, mapping, and ablation of the
      ganglionic plexi and excision of the left atrial appendage. A prospective
      multicenter registry was created to evaluate the outcomes. METHODS: The procedure
      was performed through bilateral minithoracotomies with video assistance. It
      included bilateral pulmonary vein isolation with bipolar radiofrequency with
      documentation of conduction block, location of ganglionic plexi by high-frequency
      stimulation, and appropriate ablation and left atrial appendage
      exclusion/excision. Clinical follow-up at 6 months included monitoring with
      electrocardiogram, Holter, event monitor, or pacemaker interrogation. RESULTS:
      One hundred fourteen patients with 60 (52.6%) paroxysmal, 32 (28.1%) persistent,
      and 22 (19.3%) long-standing persistent atrial fibrillations were treated. The
      mean age was 59.5 +/- 10.6 years, and 69.3% were men. The mean follow-up period
      was 204 +/- 41 days (median 195). There were 2 (1.8%) operative mortalities. At 6
      month follow-up, with long-term monitoring, 52/60 (86.7%) patients with
      paroxysmal fibrillations were in normal sinus rhythm and 43/60 (71.7%) were both
      in normal sinus rhythm and off antiarrhythmic drugs. The patients with persistent
      atrial fibrillation had a lower success rate, with 18/32 (56.3%) being in normal
      sinus rhythm and 46.9% both in normal sinus rhythm and off antiarrhythmic drugs;
      for long-standing persistent cases, 11/22 (50%) were in normal sinus rhythm and
      7/22 (31.9%) were also off antiarrhythmic drugs. CONCLUSIONS: Minimally invasive
      atrial fibrillation surgery is an effective treatment of paroxysmal atrial
      fibrillation at 6 months. Continuous event monitoring is necessary to accurately
      assess treatment results. A more extensive lesion set seems to be required for
      treatment of persistent atrial fibrillation.

PMID- 19577067
TI  - Endovascular treatment of acute and chronic aortic dissection: midterm results
      from the Talent Thoracic Retrospective Registry.
AB  - OBJECTIVE: This study examined midterm results after treatment with the
      endovascular Talent thoracic stent graft (Medtronic/AVE, Santa Rosa, Calif) in
      patients with acute or chronic aortic dissection. METHODS: In the Talent Thoracic
      Retrospective Registry, 180 patients were treated for acute or chronic aortic
      dissection (mean age: 59.6 +/- 13.0 years). Thirty-seven (20.6%) patients had
      acute aortic complications with signs of rupture, distal malperfusion, or
      persistent pain; the remainder were in stable condition. Aortic diameter was 53.5
      +/- 14.3 mm, the distance from the left subclavian artery to the proximal entry
      tear was 44.1 +/- 41.9 mm, and dissection extended beyond the celiac axis in
      88.3% of cases. Length of covered aorta measured 138.9 +/- 45.7 mm, with one
      stent graft used in 125 (69.4%) patients. RESULTS: Procedural success was 98.3%.
      Nine patients died within 30 days, yielding an overall early mortality of 5.0%.
      For in-hospital outcome, multivariate analysis showed that age greater than 75
      years (odds ratio [OR] 4,9; 95% confidence intervals [CI] 1.6-15.1; P = .006),
      American Society of Anesthesiologists class greater than III (OR 2.8; 95% CI 1.0
      7.5; P = .04), and emergency status (OR 3.5; 95% CI 1.3-8.9; P = .01) were
      independent predictors of major adverse events. Compared with electively treated
      patients, emergency status was associated with a higher incidence of in-hospital
      mortality (13.5% vs 2.1%; P = .003) and neurologic events (16.2% vs 4.2%; P =
      .01). However, patients with acute dissection had a smaller baseline diameter and
      were less often identified to have secondary endoleaks and progressive
      enlargement. Average follow-up for hospital survivors was 22.3 +/- 17.0 months
      with an estimated survival of 94.9% +/- 1.7% at 30 days, 90.6% +/- 2.3% at 12
      months, 90.6% +/- 2.3% at 24 months, and 81.8% +/- 4.8 % at 36 months. During
      follow-up, 30 patients required a total of 32 secondary interventions including
      12 open and 20 endovascular procedures, accounting for an estimated 71.5% freedom
      from reinterventions at 36 months. Follow-up imaging revealed stable or
      decreasing thoracic aortic diameter in 80.5% of patients. CONCLUSION:
      Endovascular treatment for aortic dissection is associated with reasonably low
      morbidity and mortality. Long-term surveillance is crucial to define more
      comprehensively the durability of stent graft treatment of aortic dissection and
      to determine which patients are appropriate candidates for stent graft therapy.

PMID- 19577069
TI  - Evaluation of the PAS-Port Proximal Anastomosis System in coronary artery bypass
      surgery (the EPIC trial).
AB  - OBJECTIVE: During coronary surgery, proximal vein graft anastomoses have been
      performed by using an aortic partial occlusion clamp to allow for a hand-sewn
      anastomosis. The purpose of this multicenter, prospective, randomized trial was
      to evaluate the efficacy of the PAS-Port device (Cardica, Inc, Redwood City,
      Calif), which allows an automated proximal anastomosis to be performed without
      aortic clamping. METHODS: Between June 22, 2006, and March 22, 2007, 220 patients
      requiring coronary artery bypass grafting with at least 2 vein grafts were
      enrolled. Within each patient, 1 graft was randomly assigned to receive a PAS
      Port device, and the other was assigned to receive a hand-sewn anastomosis to the
      ascending aorta. The primary end point was angiographic patency (<50% stenosis) 9
      months after surgical intervention. Secondary end points included average time to
      complete each anastomosis and 9-month freedom from major adverse cardiac events.
      RESULTS: One hundred eighty-three patients received matched grafts that were
      angiographically assessed at 9 months. The 9-month graft patency was 82.0%
      (150/183) for hand-sewn and 80.3% (147/183) for PAS-Port grafts. The patency rate
      of PAS-Port anastomoses was statistically noninferior to that of hand-sewn
      anastomoses (95% lower confidence limit for difference, -7.95%). The freedom from
      major adverse cardiac events at 9 months was 97.7% for PAS-Port (95% confidence
      interval, 94.5%-99.0%) and 98.2% for hand-sewn (95% confidence interval, 95.1%
      99.3%) grafts. The PAS-port device was associated with a 4.6 +/- 3.9-minute
      reduction in anastomotic time compared with that seen with a hand-sewn
      anastomosis (P < .001). CONCLUSIONS: The PAS-Port proximal anastomotic device
      produces an effective anastomosis with a 9-month patency rate that is comparable
      with that of a hand-sewn anastomosis. It allows for construction of a proximal
      anastomosis without aortic clamping and requires less time than a hand-sewn
      anastomosis.

PMID- 19577071
TI  - Dysfunction induced by ischemia versus edema: does edema matter?
AB  - OBJECTIVES: Recovery from pediatric cardiac surgery is affected by ischemia
      reperfusion injury, cardiac edema, and in some cases a low cardiac output
      syndrome. Although association has been made between the development of edema and
      dysfunction, modeling is confounded by intercurrent injurious stimuli that also
      cause cardiac edema and dysfunction. We tested whether a true causal relationship
      exists between edema and cardiac dysfunction. METHODS: We induced either ischemia
      or edema alone in isolated cardiomyocytes and whole Langendorff-perfused hearts.
      Function was measured as shortening dynamics and developed pressure,
      respectively. RESULTS: Ischemic injury impaired function in both cardiomyocytes
      and whole hearts. Isolated cells showed significant reduction in peak shortening
      and departure and relaxation velocities. Whole hearts displayed severely reduced
      developed pressures. Hyposmotic solution forced cardiomyocytes to swell to 7%
      greater than their normal size. No significant effect on shortening was seen.
      Similarly, Langendorff-perfused hearts were induced to take on 3% more water than
      control-perfused hearts and 9% more water than nonperfused hearts. This
      additional water was associated with mild dysfunction. CONCLUSIONS: We
      demonstrate the capacity of the heart to tolerate edema greater than that seen in
      clinical settings without residual effect. Ischemia results in ongoing
      contractile dysfunction of both isolated cardiomyocytes and whole hearts. We
      conclude that dysfunction resulting from edema in ex vivo cardiac models is mild
      and suggest review of the importance given to edema-mediated dysfunction after
      cardiac surgery.

PMID- 19577070
TI  - Real-time assessment of cardiac perfusion, coronary angiography, and acute
      intravascular thrombi using dual-channel near-infrared fluorescence imaging.
AB  - OBJECTIVES: We have developed an image-guided surgical system based on invisible
      near-infrared fluorescent light. Presently, the only clinically available near
      infrared fluorophore is indocyanine green, which fluoresces at approximately 800
      nm and is used for coronary angiography. Our objective was to determine whether
      methylene blue, already US Food and Drug Administration approved for other
      indications, has useful near-infrared fluorescence properties for image-guided
      cardiac surgery. METHODS: The optical properties of methylene blue were measured
      after dissolution in 100% serum. Biodistribution and clearance were quantified in
      organs and tissue after intravenous bolus injection of 2 mg/kg methylene blue in
      3 rats. Coronary arteriography and cardiac perfusion were imaged in real time
      after intravenous bolus injection of 1 mg/kg methylene blue in 5 pigs with
      coronary obstructions. Coronary angiography and acute thrombi were assessed by
      using 800-nm fluorophores, indocyanine green, and IR-786-labeled platelets,
      respectively. RESULTS: The peak absorbance and emission of methylene blue as a
      near-infrared fluorophore occur at 667 nm and 686 nm, respectively. After
      intravenous injection, methylene blue provides highly sensitive coronary
      angiography. A lipophilic cation, methylene blue is extracted rapidly into
      tissue, with myocardium displaying unusually high uptake. Methylene blue permits
      real-time visualization and quantitative assessment of myocardial perfusion.
      Because of absent spectral overlap, use of 2 independent fluorophores in our
      imaging system permits simultaneous quantification of perfusion, venous drainage,
      and/or intravascular thrombi. CONCLUSIONS: Methylene blue is an effective near
      infrared fluorophore that provides direct visualization of coronary arteriography
      and cardiac perfusion. In conjunction with approximately 800-nm near-infrared
      fluorophores, important functional assessments during cardiac surgery are also
      possible.

PMID- 19577072
TI  - The effect of biventricular pacing on cardiac function after weaning from
      cardiopulmonary bypass in patients with reduced left ventricular function: a
      pressure-volume loop analysis.
AB  - OBJECTIVE: Patients with severely reduced left ventricular function undergoing
      coronary artery bypass grafting have increased complication rates. We
      hypothesized that temporary postoperative atrial synchronous biventricular pacing
      would improve left ventricular function after cardiopulmonary bypass. METHODS: A
      left ventricular pressure-volume catheter was placed in 21 patients undergoing
      coronary artery bypass grafting (ejection fraction 29% +/- 5%). Pressure-volume
      loops were obtained after weaning from cardiopulmonary bypass with atrial
      synchronous biventricular, left ventricular, and right ventricular outflow tract
      pacing and atrial-only stimulation at 90 beats/min. RESULTS: Steady-state
      systolic and preload-independent parameters were superior for atrial synchronous
      biventricular and left ventricular pacing and atrial-only pacing relative to
      atrial synchronous right ventricular outflow tract pacing (P < .05). Diastolic
      parameters, excepting maximum negative rate of left ventricular pressure change,
      were unaffected. No significant differences were observed between atrial
      synchronous biventricular and left ventricular pacing and atrial-only pacing.
      Systolic dyssynchrony was significantly lower for atrial synchronous
      biventricular pacing (21% +/- 5%), atrial synchronous left ventricular pacing
      (20% +/- 6%), and atrial-only pacing (20% +/- 6%) versus atrial synchronous right
      ventricular outflow tract pacing (25% +/- 7%, P < .05). Atrioventricular interval
      during atrial-only stimulation was positively correlated with difference in
      stroke work between atrial synchronous biventricular pacing and atrial-only
      pacing (r(2) = 0.78, P > .001). CONCLUSION: Postoperative atrial synchronous
      biventricular and left ventricular pacing and atrial-only stimulation
      significantly improve systolic function relative to atrial synchronous right
      ventricular outflow tract pacing. If atrioventricular conduction is prolonged,
      atrial synchronous biventricular pacing is preferable to atrial-only pacing.

PMID- 19577073
TI  - A new de-airing technique that reduces systemic microemboli during open surgery:
      a prospective controlled study.
AB  - OBJECTIVE: We have evaluated a new technique of cardiac de-airing that is aimed
      at a) minimizing air from entering into the pulmonary veins by opening both
      pleurae and allowing lungs to collapse and b) flushing out residual air from the
      lungs by staged cardiac filling and lung ventilation. These air emboli are
      usually trapped in the pulmonary veins and may lead to ventricular dysfunction,
      life-threatening arrhythmias, and transient or permanent neurologic deficits.
      METHODS: Twenty patients undergoing elective true left open surgery were
      prospectively and alternately enrolled in the study to the conventional de-airing
      technique (pleural cavities unopened, dead space ventilation during
      cardiopulmonary bypass [control group]) and the new de-airing technique (pleural
      cavities open, ventilator disconnected during cardiopulmonary bypass, staged
      perfusion, and ventilation of lungs during de-airing [study group]).
      Transesophageal echocardiography and transcranial Doppler continually monitored
      the air emboli during the de-airing period and for 10 minutes after termination
      of the cardiopulmonary bypass. RESULTS: The amount of air embolism as observed on
      echocardiography and the number of microembolic signals as recorded by
      transcranial Doppler were significantly less in the study group during the de
      airing time (P < .001) and the first 10 minutes after termination of
      cardiopulmonary bypass (P < .001). Further, the de-airing time was significantly
      shorter in the study group (10 vs 17 minutes, P < .001). CONCLUSION: The de
      airing technique evaluated in this study is simple, reproducible, controlled,
      safe, and effective. Moreover, it is cost-effective because the de-airing time is
      short and no extra expenses are involved.

PMID- 19577075
TI  - Chronic septal infarction confers right ventricular protection during mechanical
      left ventricular unloading.
AB  - OBJECTIVE: Right ventricular failure manifests in 25% of left ventricular assist
      device recipients because of ventricular coupling mechanism disruption. Septal
      ischemia accentuates this process, but the effect of septal infarction has not
      been elucidated. Right ventricular response to incremental left ventricular
      unloading was studied in sheep with septal infarction. METHODS: Septal infarction
      was induced in 6 sheep using ethanol delivery into the main septal perforating
      artery. Six shams avoided ethanol. Load-independent and in-series right
      ventricular response to incremental (0%-100%) left ventricular unloading was
      measured 4 weeks later. Dimensions of whole heart, wall thickness, and chamber
      volumes were obtained using sonomicrometers. Selective perfusion with
      triphenyltetrazolium quantified septal damage. RESULTS: Right ventricular preload
      recruitable-stroke-work, contractility, and ejection fraction were lower at 75%
      and 100% left ventricular unloading in sham compared with infarcted animals (75%:
      26.3 +/- 3.4, 0.70 +/- 0.15, and 23.9 +/- 4.6 vs 37 +/- 2.6 erg *10;3, 0.99 +/-
      0.18 mm Hg/mL, and 35.5% +/- 3.4%, all P < . 01, 100%: 24.8 +/- 4.5, 0.67 +/-
      0.14, and 23.8 +/- 5.8 vs 36.0 +/- 4.6 erg *10;3, 0.90 +/- 0.09 mm Hg/mL, and
      32.7% +/- 11.0%, all P < . 01). Central venous pressure was higher at 75% and
      100% unloading in sham compared with infarcted animals (75%: 8.6 +/- 1.0 vs 4.5
      +/- 1.0, 100%: 12.4 +/- 0.8 vs 3.4 +/- 1.0 mm Hg, all P < . 01). Right
      ventricular cardiac output was less in shams with 100% unloading (1.2 +/- 0.2
      L/min vs 2.1 +/- 0.3 L/min, P < . 01). End-diastolic and end-systolic right
      ventricular short-axis dimension at 75% and 100% unloading was greater in sham
      compared with infarcted animals (75%: 34.4 +/- 5.5 mm and 29.1 +/- 5.5 mm vs 25.6
      +/- 4.7 mm and 20.5 +/- 4.0 mm; 100%: 37.6 +/- 6.6 mm and 29.9 +/- 5.9 mm vs 25.5
      +/- 3.9 mm and 21.1 +/- 3.8 mm, all P < .01). Prolonged diastolic relaxation
      (Tau) in infarcted animals was normalized with 75% and 100% unloading.
      CONCLUSION: High-level (>or=75%) left ventricular unloading causes right
      ventricular dilatation and compromised function. Chronic septal damage, however,
      confers protection by preserving right ventricular dimensions.

PMID- 19577074
TI  - Signal transducer and activator of transcription 3-stimulated hypoxia inducible
      factor-1alpha mediates estrogen receptor-alpha-induced mesenchymal stem cell
      vascular endothelial growth factor production.
AB  - OBJECTIVE: Vascular endothelial growth factor, a critical factor in angiogenesis,
      mediates stem cell paracrine protective effects on ischemic myocardium. Studies
      on the role of sex in stem cell function have demonstrated that female
      mesenchymal stem cells produce greater vascular endothelial growth factor and
      provide better cardiac protection compared with male mesenchymal stem cells. The
      purpose of this study was to determine the mechanisms by which estrogen affects
      mesenchymal stem cell function as a potential therapeutic measure during ex vivo
      expansion, before therapeutic use. METHODS: A single-step purification method
      using adhesion to cell culture plastic was adopted to isolate mesenchymal stem
      cells from wild-type, estrogen receptor-alpha knockout, estrogen receptor-beta
      knockout, and signal transducer and activator of transcription 3 knockout mice.
      Mesenchymal stem cells were treated with or without 17beta-estradiol, estrogen
      receptor-alpha agonist (propyl pyrazoletriol), and estrogen receptor-beta agonist
      (diarylpropionitrile). RESULTS: 17beta-estradiol significantly increased
      mesenchymal stem cell vascular endothelial growth factor production in a dose
      dependent manner. Both estrogen receptor-alpha and estrogen receptor-beta were
      expressed in mesenchymal stem cells. Administration of 17beta-estradiol or
      estrogen receptor-alpha agonist (not estrogen receptor-beta agonist) elevated
      mesenchymal stem cell vascular endothelial growth factor, hypoxia inducible
      factor-1alpha expression, and signal transducer and activator of transcription 3
      activation. However, these effects were neutralized in estrogen receptor-alpha
      knockout mesenchymal stem cells, not estrogen receptor-beta knockout. Signal
      transducer and activator of transcription 3 knockout abolished estrogen receptor
      alpha-induced hypoxia inducible factor-1alpha and subsequent vascular endothelial
      growth factor production. CONCLUSION: 17beta-estradiol-induced vascular
      endothelial growth factor production from mesenchymal stem cells appears to be
      mediated through estrogen receptor-alpha-activated signal transducer and
      activator of transcription 3-mediated hypoxia inducible factor-1alpha expression.

PMID- 19577076
TI  - Diagnostic value of endobronchial ultrasonography for pulmonary tuberculosis.
AB  - OBJECTIVES: We sought to compare the diagnostic yields of acid-fast bacilli
      smears and Mycobacterium tuberculosis cultures in terms of bronchoalveolar lavage
      fluid and histologic examination of transbronchial lung biopsy specimens for
      pulmonary tuberculosis by using bronchoscopy with versus without endobronchial
      ultrasonography in patients with negative acid-fast bacilli smears or no sputum
      production. METHODS: From June 2005 to July 2006, a total of 451 patients were
      given diagnoses of and treated for pulmonary tuberculosis in a university
      affiliated hospital. Among them, 121 patients who received bronchoscopy because
      of sputum-negative conditions were recruited. Of these, 73 patients received
      bronchoscopy with endobronchial ultrasonography, and 48 patients received
      conventional bronchoscopy. RESULTS: Patients who received bronchoscopy with
      endobronchial ultrasonography had higher diagnostic yields of acid-fast bacilli
      smears (31.5% vs 12.5%, P = .018) in bronchoalveolar lavage fluid, M tuberculosis
      in bronchoalveolar lavage fluid (67.1% vs 47.9%, P = .024), and pathologic
      reports of tuberculosis in transbronchial lung biopsy specimens (32.9% vs 4.2%, P
      < .0001) than patients who received conventional bronchoscopy. With the aid of
      endobronchial ultrasonography, the overall diagnostic yield for tuberculosis by
      using bronchoscopic procedures (smears and cultures of bronchoalveolar lavage
      fluid and transbronchial lung biopsy specimens) was higher (80.8%) than for those
      who did not undergo endobronchial ultrasonography (58.3%, P = .035). CONCLUSIONS:
      The addition of endobronchial ultrasonography to diagnostic bronchoscopy
      increased the sensitivity for proving the presence of tuberculosis in a
      population of patients with negative acid-fast bacilli smears or no sputum
      production.

PMID- 19577077
TI  - Increased vascular permeability after cardiopulmonary bypass in patients with
      diabetes is associated with increased expression of vascular endothelial growth
      factor and hepatocyte growth factor.
AB  - BACKGROUND: Several inflammatory mediators such as vascular endothelial growth
      factor and hepatocyte growth factor are known to play a critical role in the
      regulation of vascular permeability and angiogenesis. We studied the serum levels
      of growth factors and gene expression profiles of genes involved in growth factor
      signaling in the peripheral blood of patients with and patients without diabetes
      following cardiopulmonary bypass and cardioplegic arrest. METHODS: Serum and
      total RNA were obtained from the blood samples collected from patients with
      diabetes and matched patients without diabetes (n = 7 patients each) who had
      coronary artery bypass graft before and 6 hours and 4 days after cardiopulmonary
      bypass/cardioplegic arrest. The cytokine panel, consisting of growth factors such
      as vascular endothelial growth factor, hepatocyte growth factor, fibroblast
      growth factor, and epidermal growth factor, was quantified in patients with
      diabetes and patients without diabetes before and 6 hours and 4 days post
      cardiopulmonary bypass/cardioplegic arrest using multiplex cytokine
      quantification system. cDNA microarray analysis was performed and fold-change was
      calculated. RESULTS: Length of hospitalization (10 vs 6 days; P = .04) and weight
      gain (5 vs 2.5 kg; P = .001) were significantly greater for patients with
      diabetes compared with patients without diabetes. The serum levels of vascular
      endothelial growth factor and hepatocyte growth factor were significantly
      elevated in patients with diabetes when compared with patients without diabetes
      before versus 6 hours post-cardiopulmonary bypass/cardioplegic arrest. In
      addition, significantly elevated mRNA expression of hypoxia-inducible factor
      1alpha, cyclic adenosine monophosphate response element binding protein, and E1A
      binding protein p300 (more than twofold) was observed 4 days post-cardiopulmonary
      bypass/cardioplegic arrest exclusively in patients with diabetes. CONCLUSIONS:
      The differential profile of gene and protein expression of growth factors and
      their related genes in patients with diabetes and patients without diabetes could
      be associated with increased edema and weight gain in patients with diabetes
      after cardiopulmonary bypass/cardioplegic arrest.

PMID- 19577079
TI  - Correlation between plasma osteopontin levels and aortic valve calcification:
      potential insights into the pathogenesis of aortic valve calcification and
      stenosis.
AB  - OBJECTIVE: The inflammatory process of aortic stenosis involves the
      differentiation of aortic valve myofibroblasts into osteoblasts. Osteopontin, a
      proinflammatory glycoprotein, both stimulates differentiation of myofibroblasts
      and regulates the deposition of calcium by osteoblasts. Osteopontin levels are
      increased in patients with such conditions as end-stage renal disease, ectopic
      calcification, and autoimmune disease. We hypothesized that increased plasma
      osteopontin levels might be associated with the presence of aortic valve
      calcification and stenosis. METHODS: Venous blood from volunteers older than 65
      years undergoing routine echocardiographic analysis or aortic valve surgery for
      aortic stenosis was collected. Plasma osteopontin levels were measured by means
      of enzyme-linked immunosorbent assay. The presence of aortic stenosis was defined
      as an aortic valve area of less than 2.0 cm(2). Aortic valve calcification was
      assessed by using a validated echocardiographic grading system (1, none; 2, mild;
      3, moderate; 4, severe). Comparisons were performed with nonpaired t tests.
      RESULTS: Aortic stenosis was present in 23 patients (mean age, 78 years) and was
      absent in 7 patients (mean age, 72 years). Aortic valve calcification scores were
      3.5 +/- 0.6 and 1.3 +/- 0.5 in patients with and without aortic stenosis,
      respectively (P < .001). Patients with no or mild aortic valve calcification had
      lower osteopontin levels compared with patients with moderate or severe aortic
      valve calcification (406.1 +/- 165.8 vs 629.5 +/- 227.5 ng/mL, P = .01).
      Similarly, patients with aortic stenosis had higher osteopontin levels compared
      with patients without aortic stenosis (652.2 +/- 218.7 vs 379.7 +/- 159.9 ng/mL,
      P < .01). CONCLUSION: Increased levels of plasma osteopontin are associated with
      the presence of aortic valve calcification and stenosis. These findings suggest
      that osteopontin might play a functional role in the pathogenesis of calcific
      aortic stenosis.

PMID- 19577078
TI  - The impact of smoking in primary spontaneous pneumothorax.
AB  - BACKGROUND: The crucial role of cigarette smoking in the development of
      pneumothorax is unclear because nonsmokers can also develop primary spontaneous
      pneumothorax. The purpose of this study was to clarify the pathophysiologic
      effects of cigarette smoking and its clinical correlations in primary spontaneous
      pneumothorax. METHODS: Included were 115 specimens of lung tissue from patients
      with primary spontaneous pneumothorax who underwent video-assisted thoracoscopic
      surgery from January 2001 to December 2002. We reviewed the clinical features of
      56 smokers and 59 nonsmokers with an average follow-up of 67 months. The
      pathologic findings of resected lung specimens were analyzed retrospectively.
      RESULTS: There were no statistical differences in sex, age, body height, body
      weight, body mass index, or the presence of blebs/bullae on computed tomography
      scans of the lung or under thoracoscopy between the 2 groups. In the smoking
      group, patients had more extensive respiratory bronchiolitis (P < .001), a high
      prevalence of tobacco pigmentation (P < .001), and a higher recurrence rate
      without or after surgery than the nonsmoking group (57% vs 22%, P = .001 and 8.9%
      vs 1.7%, P = .02, respectively). Patients with extensive respiratory
      bronchiolitis had significantly higher nonoperative and postoperative recurrences
      than patients with nonextensive respiratory bronchiolitis (P = .004 and P < .001,
      respectively). CONCLUSION: Cigarette smoking is associated with the
      pathophysiologic consequences of extensive respiratory bronchiolitis, which had a
      significant impact on the recurrence rates of primary spontaneous pneumothorax.

PMID- 19577080
TI  - Uric acid levels and outcome from coronary artery bypass grafting.
AB  - OBJECTIVE: Elevated uric acid levels have been associated with an adverse
      cardiovascular outcome in several settings. Their utility in patients undergoing
      surgical revascularization has not, however, been assessed. We hypothesized that
      serum uric acid levels would predict the outcome of patients undergoing coronary
      artery bypass grafting. METHODS: The study cohort consisted of 1140 consecutive
      patients undergoing nonemergency coronary artery bypass grafting. Clinical
      details were obtained prospectively, and serum uric acid was measured a median of
      1 day before surgery. The primary end point was all-cause mortality. RESULTS:
      During a median of 4.5 years, 126 patients (11%) died. Mean (+/- standard
      deviation) uric acid levels were 390 +/- 131 micromol/L in patients who died
      versus 353 +/- 86 micromol/L among survivors (hazard ratio 1.48 per 100
      micromol/L; 95% confidence interval, 1.25-1.74; P < .001). The excess risk
      associated with an elevated uric acid was particularly evident among patients in
      the upper quartile (>or=410 micromol/L; hazard ratio vs all other quartiles
      combined 2.18; 95% confidence interval, 1.53-3.11; P < .001). After adjusting for
      other potential prognostic variables, including the European System for Cardiac
      Operative Risk Evaluation, uric acid remained predictive of outcome. CONCLUSION:
      Increasing levels of uric acid are associated with poorer survival after coronary
      artery bypass grafting. Their prognostic utility is independent of other
      recognized risk factors, including the European System for Cardiac Operative Risk
      Evaluation.

PMID- 19577082
TI  - Vascular abnormalities and cardiomyocyte lipofuscin deposits in endomyocardial
      biopsy specimens of heart transplant recipients: are they related to the
      development of cardiac allograft vasculopathy?
AB  - OBJECTIVE: The aim of this study was to assess the predictive value of
      microvascular abnormalities and lipofuscin observed in endomyocardial biopsy
      samples for the development of cardiac allograft vasculopathy. METHODS: The study
      group consisted of 68 cardiac allograft recipients (63 men and 5 women, 43 +/- 12
      years old). We performed a re-evaluation of 1071 endomyocardial biopsy specimens
      to search for microvascular diseases and lipofuscin in cardiocytes.
      Endomyocardial biopsy specimens with an International Society for Heart and Lung
      Transplantation rejection grade of 2 or more and those without arterioles were
      excluded. Abnormalities found in the remaining 517 specimens were correlated with
      the grade of rejection. Biopsy specimens obtained 2 weeks, 12 months, and 36
      months after transplantation were compared with coronary angiography results,
      clinical events of cardiac allograft vasculopathies, and survivals. Kaplan-Meier
      curves were constructed to compare the time to the development of cardiac
      allograft vasculopathy or death. RESULTS: Enlarged endothelial cells, lymphocytes
      inside the arteriolar wall, occluded arteriolar lumen, endothelial vacuolization,
      and hypertrophy of the vascular muscle were significantly correlated with
      rejection grade. Although none of the vascular abnormalities predicted cardiac
      allograft vasculopathy, patients with lipofuscin deposits at the 12-month biopsy
      specimens were characterized by the rapid development of angiography-confirmed
      cardiac allograft vasculopathy (P < .08) and events related to cardiac allograft
      vasculopathy (P < .03, log-rank test). CONCLUSION: Microvascular abnormalities
      correlate with mild cellular rejection, but they do not seem to be predictive for
      development of cardiac allograft vasculopathy detected by angiography. The
      presence of lipofuscin in 12-month endomyocardial biopsy specimens may be
      predictive of development of angiographically confirmed cardiac allograft
      vasculopathy.

PMID- 19577081
TI  - The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative
      stress and inflammatory response in cyanotic pediatric patients undergoing open
      cardiac surgery: a randomized controlled trial.
AB  - OBJECTIVES: This study investigates the effects of controlled reoxygenation
      cardiopulmonary bypass on oxidative stress, inflammatory response, and organ
      function in children undergoing repair of cyanotic congenital heart defects.
      METHODS: Sixty-seven cyanotic patients (median age 15 months, interquartile range
      6-49 months) undergoing corrective cardiac surgery were randomized to receive
      either controlled normoxic (50-0 mm Hg; n = 35) or hyperoxic (150-180 mm Hg; n =
      32) cardiopulmonary bypass. Troponin I and 8-isoprostane, C3a, interleukins 6, 8,
      and 10, cortisol, protein S100, and alpha-glutamate transferase were measured
      preoperatively and 10 and 30 minutes after starting bypass, on removal of the
      aortic crossclamp, and 12 and 24 hours thereafter. RESULTS: Overall, troponin I
      and 8-isoprostane levels were lower in the controlled normoxic group (-29%, 95%
      CI -48% to -3%, P = .03, and -26%, 95% CI -44% to -2%, P = .03, respectively).
      Protein S100 release was also lower in the normoxic group 10 minutes after
      starting bypass (-26%, 95% CI -40% to -9%, P = .005) and 10 minutes after aortic
      crossclamp removal (-23%, 95% CI -38% to -3%, P = .02, respectively), but similar
      at other time points in the two groups (P >or= .17). The alpha-glutamate
      transferase release was significantly lower in the normoxic group 10 minutes
      after aortic crossclamp removal (-28%, 95% CI -44% to -9%, P = .006,
      respectively) but was similar at other times (P >or= .11). Release of C3a,
      interleukins 6, 8, and 10, and cortisol was similar in the two groups throughout
      (P >or= .15). CONCLUSION: Controlled reoxygenation on starting cardiopulmonary
      bypass is associated with reduced myocardial damage, oxidative stress, and
      cerebral and hepatic injury compared with hyperoxic bypass and similar whole body
      inflammatory and stress response in cyanotic children undergoing open cardiac
      surgery.

PMID- 19577083
TI  - Right but not left ventricular function recovers early after living-donor lobar
      lung transplantation in patients with pulmonary arterial hypertension.
AB  - OBJECTIVE: The aim of this study was to evaluate right and left ventricular
      functions in patients with pulmonary arterial hypertension after living-donor
      lobar lung transplantation compared with those without hypertension. METHODS:
      Thirty-three recipients of living-donor lobar lung transplantation were divided
      into two groups: those with pulmonary arterial hypertension (PAH group; n = 12)
      and those without (non-PAH group; n = 21). Their systolic pulmonary artery
      pressure was 93.1 +/- 6.7 mm Hg versus 31.4 +/- 2.9 mm Hg, respectively. Right
      and left ventricular ejection fractions, systolic pulmonary artery pressure, and
      cardiac index were serially measured by radionuclide ventriculography and right
      heart catheterization, respectively. RESULTS: Pretransplant right and left
      ventricular ejection fractions were lower in the PAH group (29.8% +/- 7.0%, 49.9%
      +/- 6.6%) than in the non-PAH group (49.7% +/- 3.3%, 65.2% +/- 1.9%) (P = .010,
      .068). Two months after living-donor lobar lung transplantation, right
      ventricular ejection fraction and systolic pulmonary artery pressure in the PAH
      group (57.3% +/- 5.1%, 25.7 +/- 1.8 mm Hg) improved dramatically, equal to those
      in the non-PAH group. In contrast, left ventricular ejection fraction and cardiac
      index in the PAH group (50.9% +/- 3.7%, 2.66 +/- 0.12 L x min(-1) x m(-2)) were
      still significantly lower than in the non-PAH group (65.4% +/- 2.8%, 3.13 +/-
      0.15 L x min(-1) x m(-2)) (P = .0038, .037). At 6 to 12 months, the PAH group
      demonstrated a significant rise in left ventricular ejection fraction and cardiac
      index that reached similar values in the non-PAH group measured at 2 months.
      These values were stable for up to 3 years. CONCLUSIONS: Right ventricular
      function recovered early after living-donor lobar lung transplantation in the PAH
      group. In contrast, recovery of left ventricular function required 6 to 12
      months. Improved cardiac function was sustained for up to 3 years, suggesting
      long-term durability of cardiac function recovery after living-donor lobar lung
      transplantation.

PMID- 19577084
TI  - Bridging patients after salvage from bridge to decision directly to transplant by
      means of prolonged support with the CentriMag short-term centrifugal pump.
AB  - OBJECTIVE: Optimum strategy for salvage in patients with acutely decompensated
      end-stage heart failure and severe multiorgan dysfunction is complex. We present
      our experience with prolonged CentriMag (Levitronix, Waltham, Mass) support for
      transitioning patients after successful salvage from bridge to decision directly
      to transplant. METHODS: Records of patients who underwent salvage with a
      CentriMag as bridge to decision and later to transplant were reviewed. Between
      June 2003 and June 2008, 4 patients in cardiogenic shock from acute decompensated
      end-stage heart failure and multiorgan dysfunction underwent salvage with
      biventricular CentriMag as bridge to decision. Three were male. Mean age was 39.3
      years (range 24-52 years). Three had dilated cardiomyopathy; 1 had ischemic
      cardiomyopathy. All had preoperative mechanical ventilation, large doses of
      multiple inotropes, and intra-aortic balloon support. All also had acute liver
      and renal failure and metabolic acidosis. RESULTS: After mean postimplant period
      of 43 days (range 7-70 days), patients had reversal of end-organ dysfunction;
      after mean waiting time of 31 days (range 21-67 days), all were transplant
      listed. Mean mechanical circulatory support was 87.7 days (range 26-105 days). No
      thromboembolic or neurologic events or mechanical failures occurred.
      Posttransplant mean ventilation and intensive care unit stay were 2 and 4 days
      (ranges 1-4 and 3-7 days), respectively. All patients were discharged home and
      remain alive and well. CONCLUSION: CentriMag use as long as 3 months appears to
      be safe and cost-effective for bridging selected patients directly to transplant
      after salvage. Further clinical experience is still needed.

PMID- 19577085
TI  - A difficult case: ectopic thyroid, bronchial anomalies, and incidentaloma in a
      patient with lung carcinoma.

PMID- 19577086
TI  - Potential for benefits of aprotinin use to outweigh risks in patients undergoing
      the Ross procedure.

PMID- 19577087
TI  - Left main compression syndrome by idiopathic pulmonary artery aneurysm caused by
      medial necrosis Erdheim-Gsell combined with bicuspid pulmonary valve.

PMID- 19577088
TI  - Aortic pseudoaneurysm compressing the left coronary artery.

PMID- 19577089
TI  - Persistent interstitial pulmonary emphysema requiring pneumonectomy.

PMID- 19577090
TI  - Surgical resection of resectable thoracic metastatic hepatocellular carcinoma
      after liver transplantation.

PMID- 19577091
TI  - Radio-guided surgery for ventricular remodeling in patients with ischemic dilated
      cardiomyopathy: a new tool to discriminate in vivo viable myocardium and scar.

PMID- 19577092
TI  - "Circular clamp" excision: a new technique for lung metastasectomy.

PMID- 19577093
TI  - Combined use of extracorporeal membrane oxygenation and activated protein C for
      severe acute respiratory distress syndrome and septic shock.

PMID- 19577094
TI  - The first self-endothelialized titanium-coated glutaraldehyde-fixed heart valve
      prosthesis within systemic circulation.

PMID- 19577099
TI  - Quality improvement program decreases mortality after cardiac surgery.

PMID- 19577095
TI  - Axillary artery cannulation pitfalls.

PMID- 19577098
TI  - Endoscopic treatment of airway stenosis after lung transplantation.

PMID- 19577101
TI  - Transmission of human T-lymphotropic virus type I by bilateral living-donor lobar
      lung transplantation.

PMID- 19577102
TI  - Does hypercholesterolemia improve operative outcomes in patients without coronary
      artery disease who undergo cardiac surgery?

PMID- 19577104
TI  - Hypoxia-inducible factor-1alpha in stem cell preconditioning: mechanistic role of
      hypoxia-related micro-RNAs.

PMID- 19577105
TI  - The implications of outcome predictors when transitioning from arterial to double
      switch surgery.

PMID- 19577106
TI  - Contegra and extracardiac Fontan.

PMID- 19577107
TI  - Late rupture of expanded polytetrafluoroethylene neochordae used for mitral valve
      repair.

PMID- 19577108
TI  - Biventricular pacing after cardiac surgery.

PMID- 19577109
TI  - Prognostic significance of visceral pleural invasion and tumor size in non-small
      cell lung cancer.

PMID- 19577110
TI  - Percutaneous aortic valve implantation: what does oversizing mean?

PMID- 19577112
TI  - Mechanism of myocardial protection by pressure-volume unloading involves stretch
      induced pathophysiology.

PMID- 19577111
TI  - Serum brain natriuretic peptide for prediction of successful medical treatment of
      patent ductus arteriosus in premature infants.

PMID- 19577113
TI  - Care of the cirrhotic patient. Preface.

PMID- 19577114
TI  - Diagnosis and epidemiology of cirrhosis.
AB  - Cirrhosis is defined histologically as an advanced form of progressive hepatic
      fibrosis with distortion of the hepatic architecture and regenerative nodule
      formation. It may be due to a variety of causes. It can be diagnosed incidentally
      on liver biopsy or hepatic imaging studies, or patients may present clinically
      with one or more features of hepatic failure. This article gives the reader a
      broad overview of the epidemiology, diagnosis, and natural history of cirrhosis;
      laying the foundation for subsequent articles, which will discuss the diagnosis
      and management of each of the specific cirrhosis-related complications.

PMID- 19577115
TI  - Ascites: diagnosis and management.
AB  - Ascites is the pathologic accumulation of fluid in the peritoneal cavity and is a
      common manifestation of liver failure, being one of the cardinal signs of portal
      hypertension. The diagnostic evaluation of ascites involves an assessment of its
      cause by determining the serum-ascites albumin gradient and the exclusion of
      complications eg, spontaneous bacterial peritonitis. Although sodium restriction
      and diuretics remain the cornerstone of ascites management, many patients require
      additional therapy when they become refractory to such medical treatment. These
      include repeated large volume paracentesis and transjugular intrahepatic
      portosystemic shunts. This review article summarizes diagnostic tools and
      provides an evidence-based approach to the management of ascites.

PMID- 19577116
TI  - Hepatic encephalopathy: pathophysiology and emerging therapies.
AB  - Hepatic encephalopathy is characterized by neuropsychiatric abnormalities in
      patients with liver failure. Severe hepatic encephalopathy is an indication for
      liver transplantation as it portends poor outcome. Treatment of hepatic
      encephalopathy involves correction of precipitating factors such as sepsis,
      gastrointestinal bleeding, medications, and electrolyte imbalance. Effective
      therapies include lactulose and antibiotics such as neomycin, metronidazole, and
      rifaximin.

PMID- 19577117
TI  - Portal hypertension and variceal hemorrhage.
AB  - Portal hypertension is a progressively debilitating complication of cirrhosis and
      a principal cause of mortality in patients who have hepatic decompensation. This
      article describes the classification system and pathophysiology of portal
      hypertension. It also discusses a practical approach to prevention of first
      variceal hemorrhage, general management of the acute bleeding episode, and
      secondary prophylaxis to prevent rebleeding. Pharmacologic, endoscopic,
      radiologic, and surgical modalities are all described in detail.

PMID- 19577118
TI  - Renal failure in patients with cirrhosis.
AB  - Renal failure in cirrhosis poses unique diagnostic and therapeutic challenges.
      Laboratory values and predictive equations grossly overestimate renal function in
      patients with cirrhosis. Development of renal failure connotes a worse prognosis;
      mortality is especially high with hepatorenal syndrome. Classification of the
      causes of renal failure in patients with cirrhosis is provided with more
      extensive discussion of selected causes. Finally, a suggested diagnostic approach
      to renal failure in cirrhosis is given.

PMID- 19577119
TI  - Pulmonary complications of cirrhosis.
AB  - Advanced liver disease and portal hypertension produce various intrathoracic
      complications that involve the pleural space, the lung parenchyma, and the
      pulmonary circulation. Dyspnea and arterial hypoxemia are the most common
      symptoms and signs in patients with such complications. This article focuses on
      the diagnosis and management of hepatopulmonary syndrome, portopulmonary
      hypertension, and hepatic hydrothorax. All are pulmonary processes associated
      with end-stage liver disease that lead to significant morbidity and affect the
      quality of life of patients who are suffering from liver cirrhosis.

PMID- 19577120
TI  - Current management of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), one of the most common cancers worldwide,
      continues to increase in incidence in several regions around the world and is
      associated with poor overall survival. Patients with cirrhosis are at the highest
      risk and are candidates for surveillance. Wide implementation of surveillance
      programs and improvement in noninvasive radiologic techniques has led to tumor
      diagnosis at earlier stages. Surgical options that include resection and liver
      transplantation offer the best chance of successful outcomes. Locoregional
      therapies, such as radiofrequency ablation and chemoembolization, provide
      effective local control in those with acceptable hepatic function. A multikinase
      inhibitor, sorafenib, is the first molecular targeted oral therapy that has
      recently been shown to provide a survival benefit in HCC in select patients.

PMID- 19577121
TI  - Health maintenance issues in cirrhosis.
AB  - Caring for patients with cirrhosis requires special consideration. The role of
      the hepatologist is to assist the primary care physician in caring for such
      patients. This involves an active role in immunizations, lifestyle modifications,
      and providing instructions on when to go to the emergency room (ER). There are
      also specific recommendations geared toward the patient with cirrhosis relating
      to slowing down the disease process, maintaining quality of life, and improving
      survival.

PMID- 19577122
TI  - Preoperative risk assessment for patients with liver disease.
AB  - Patients with underlying liver disease often present for non-liver-related
      surgery and are at risk for postoperative decompensation. Several predictive
      models exist to determine the risk of morbidity and mortality after surgery in
      such patients, but the risk depends on the severity of liver disease and also the
      type and urgency of the surgery. Clinicians should be cognizant of the various
      risk assessment tools and incorporate them into their practice when encountering
      patients with liver disease undergoing surgery.

PMID- 19577123
TI  - Liver transplantation: from Child to MELD.
AB  - The widespread availability of transplantation in most major medical centers in
      the United States, together with a growing number of transplant candidates, has
      made it necessary for primary care providers, especially internal medicine and
      family practice physicians to be active in the clinical care of these patients
      before and after transplantation. This review provides an overview of the liver
      transplantation process, including indications, contraindications, time of
      referral to a transplant center, the current organ allocation system, and briefly
      touches on the expanding field of living donor liver transplantation.

PMID- 19577125
TI  - Create your own stimulus package and improve access to care.

PMID- 19577127
TI  - Timely observations on friction and sliding.

PMID- 19577128
TI  - Computed tomography in rapid palatal expansion.

PMID- 19577129
TI  - Understanding friction and sliding.

PMID- 19577132
TI  - Physical properties of root cementum: part 11. Continuous vs intermittent
      controlled orthodontic forces on root resorption. A microcomputed-tomography
      study.
AB  - INTRODUCTION: There is still ambiguity about whether continuous or intermittent
      orthodontic forces produce more root resorption. This prospective randomized
      clinical trial was designed to compare root resorption with these 2 force
      application patterns. METHODS: The sample consisted of 16 maxillary first
      premolars from 8 patients who required bilateral extractions as part of their
      orthodontic treatment. In each subject, a fixed experimental appliance was placed
      on the maxillary teeth on each side, allowing a buccally directed force. The
      force was generated by a segmental wire of beta-titanium-molybdenum alloy. The
      first premolar on 1 side received a buccally directed continuous force, and the
      contralateral premolar received intermittent force. The initial force magnitude
      for both sides was 225 cN. After 14 days of initial continuous force, the
      intermittent force application was obtained with subsequently repeated periods
      until the end of the eighth week of a 3-day rest period followed by a 4-day force
      application period. Force levels were set to 225 cN at each patient visit. After
      the experimental period of 8 weeks, the teeth were extracted under a strict
      protocol to prevent root surface damage and analyzed with a microcomputed
      tomography scan system, and specially designed software was used for direct
      volumetric measurements. RESULTS: Intermittent force produced less root
      resorption than continuous force (P <0.05). Analysis by position showed that the
      buccal-cervical region had significantly more root resorption than the other
      positions (P <0.001), corresponding to a region of compression generated by
      tipping. CONCLUSIONS: The application of intermittent orthodontic forces of 225
      cN for 8 weeks (14 days of force application, 3 days of rest, then 4 days of
      force application repeated for 6 weeks) caused less root resorption than
      continuous forces of 225 cN for 8 weeks. Although it might not be clinically
      practical, compared with continuous forces, intermittent forces might be a safer
      method to prevent significant root resorption. This regimen, however, could
      compromise the efficiency of tooth movement.

PMID- 19577134
TI  - Gastroesophageal reflux symptoms in adults with skeletal Class III malocclusion
      examined by questionnaires.
AB  - INTRODUCTION: Patients with masticatory dysfunction have a higher incidence of
      gastrointestinal disorders including gastroesophageal reflux disease (GERD).
      Masticatory function is significantly lower in patients with skeletal Class III
      malocclusion than in those with normal occlusion. However, GERD symptoms in
      patients with skeletal Class III malocclusion are still unknown. The purpose of
      this study was to examine GERD symptoms and masticatory functions in patients
      with skeletal Class III malocclusion. METHODS: Nineteen adult patients with
      severe skeletal Class III malocclusion (Class III group) and 20 adults with
      normal occlusion (control group) participated in this study. The results of the
      Carlsson-Dent self-administered questionnaire (QUEST) and the frequency scale for
      the symptoms of GERD (FSSG) were compared between the 2 groups, along with
      occlusal contact area, maximal voluntary bite force, and salivary flow rate.
      RESULTS: The QUEST and FSSG scores were significantly higher in the Class III
      group. Occlusal contact area and maximal voluntary bite force were significantly
      smaller in the Class III group. There was no significant difference in the
      salivary flow rates between the groups. CONCLUSIONS: GERD symptoms were observed
      more often in patients with skeletal Class III malocclusion than in normal
      subjects as determined by the questionnaires.

PMID- 19577136
TI  - Influence of thermoplastic appliance thickness on the magnitude of force
      delivered to a maxillary central incisor during tipping.
AB  - INTRODUCTION: The aim of the study was to quantify the forces delivered by
      thermoplastic appliances made of 2 materials with 2 thicknesses to a maxillary
      central incisor during tipping. METHODS: Two materials were tested, each in 2
      thicknesses: Erkodur (Erkodent Erich Kopp GmbH, Pfalzgrafenweiler, Germany) 1.0
      and 0.8 mm, and Biolon (Dreve Dentamid GmbH, Unna, Germany), 1.0 and 0.75 mm. For
      each material, 5 appliances were produced. To measure the forces applied, an
      isolated measuring tooth, part of a standardized resin model, was deflected in
      0.05 degrees steps from 0 degrees to 0.42 degrees in the vestibular and palatine
      directions, after placing the respective appliance on the model. For statistical
      analysis, the force components Fx/tipping and Fz/intrusion at a displacement of
      +/- 0.151 mm from the incisor edge were selected. Means and standard deviations
      were calculated. The Wilcoxon 2-sample test for group pairings was used. RESULTS:
      The norms for the mean Fx forces ranged from 1.62 (SD, 0.41) to 5.35 N (SD,
      0.63). The mean Fz forces were between 0.07 (SD, 0.13) and -2.47 N (SD, 0.34).
      The highest intrusive forces were measured during vestibular displacement of the
      measuring tooth. The forces delivered by the thick appliances were overall
      significantly higher (P <0.0001) than those of the thin materials. The forces
      delivered by the Biolon appliances were generally significantly higher (P
      <0.0001) than those for the Erkodur materials. CONCLUSIONS: The forces applied
      were mostly too high when compared with those stated in the literature as ideal.
      In addition to thickness, the thermoforming process influences the magnitude of
      the force delivered by a thermoformed appliance.

PMID- 19577138
TI  - Effect of dental arch convexity and type of archwire on frictional forces.
AB  - INTRODUCTION: Friction measurements in orthodontics are often derived from models
      by using brackets placed on flat models with various straight wires. Dental
      arches are convex in some areas. The objectives of this study were to compare the
      frictional forces generated in conventional flat and convex dental arch setups,
      and to evaluate the effect of different archwires on friction in both dental arch
      models. METHODS: Two stainless steel models were designed and manufactured
      simulating flat and convex maxillary right buccal dental arches. Five stainless
      steel brackets from the maxillary incisor to the second premolar (slot size, 0.22
      in, Victory, 3M Unitek, Monrovia, Calif) and a first molar tube were aligned and
      clamped on the metal model at equal distances of 6 mm. Four kinds of orthodontic
      wires were tested: (1) A. J. Wilcock Australian wire (0.016 in, G&H Wire,
      Hannover, Germany); and (2) 0.016 x 0.022 in, (3) 0.018 x 0.022 in, and (4) 0.019
      x 0.025 in (3M Unitek GmbH, Seefeld, Germany). Gray elastomeric modules (Power O
      110, Ormco, Glendora, Calif) were used for ligation. Friction tests were
      performed in the wet state with artificial saliva lubrication and by pulling 5 mm
      of the whole length of the archwire. Six measurements were made from each bracket
      wire combination, and each test was performed with new combinations of materials
      for both arch setups (n = 48, 6 per group) in a universal testing machine
      (crosshead speed: 20 mm/min). RESULTS AND CONCLUSIONS: Significant effects of
      arch model (P = 0.0000) and wire types (P = 0.0000) were found. The interaction
      term between the tested factors was not significant (P = 0.1581) (2-way ANOVA and
      Tukey test). Convex models resulted in significantly higher frictional forces
      (1015-1653 g) than flat models (680-1270 g) (P <0.05). In the flat model,
      significantly lower frictional forces were obtained with wire types 1 (679 g) and
      3 (1010 g) than with types 2 (1146 g) and 4 (1270 g) (P <0.05). In the convex
      model, the lowest friction was obtained with wire types 1 (1015 g) and 3 (1142 g)
      (P >0.05). Type 1 wire tended to create the least overall friction in both flat
      and convex dental arch simulation models.

PMID- 19577140
TI  - Comparison of space analysis evaluations with digital models and plaster dental
      casts.
AB  - INTRODUCTION: Diagnostic measurements have traditionally been made on plaster
      dental casts. Now, 3-dimensional digital dental models can be used. The purpose
      of this study was to compare space analysis measurements made on digital models
      with those from plaster dental casts. METHODS: Two sets of 25 alginate
      impressions were taken of patients who had a permanent Class I crowded dentition.
      Each impression was made into a plaster cast and a 3-dimensional virtual
      orthodontic model (OrthoCad, Cadent, Fairview, NJ). Measurements of tooth widths
      at their greatest mesiodistal dimension and arch length were recorded for both
      types of models. Tooth widths were measured on the plaster models with a digital
      caliper, and arch length was measured with a piece of brass wire and a millimeter
      ruler. The virtual models were measured by using OrthoCad's dedicated software.
      The space analysis measurements were calculated for both types of models, and the
      extrapolated amount of crowding for each type of model was accessed. All
      measurements were made by 2 examiners. The resulting values were compared with
      nonparametric statistics, and method errors were calculated. RESULTS: When
      comparing digitized models with conventional plaster dental study models, we
      found a slight (0.4 mm) but statistically significant difference in the space
      analysis measurements on the maxillary models; measurements on the mandibular
      models were not significantly different. No significant difference was found
      between the measurements of the 2 examiners. CONCLUSIONS: The accuracy of the
      software for space analysis evaluation on digital models is clinically acceptable
      and reproducible when compared with traditional plaster study model analyses.

PMID- 19577142
TI  - Accuracy and reliability of linear cephalometric measurements from cone-beam
      computed tomography scans of a dry human skull.
AB  - INTRODUCTION: The purpose of this study was to determine the accuracy and
      reliability of 3-dimensional craniofacial measurements obtained from cone-beam
      computed tomography (CBCT) scans of a dry human skull. METHODS: Seventeen
      landmarks were identified on the skull. CBCT scans were then obtained, with 2
      skull orientations during scanning. Twenty-nine interlandmark linear measurements
      were made directly on the skull and compared with the same measurements made on
      the CBCT scans. All measurements were made by 2 operators on 4 separate
      occasions. RESULTS: The method errors were 0.19, 0.21, and 0.19 mm in the x-, y-
      and z-axes, respectively. Repeated measures analysis of variance (ANOVA) showed
      no significant intraoperator or interoperator differences. The mean measurement
      error was -0.01 mm (SD, 0.129 mm). Five measurement errors were found to be
      statistically significantly different; however, all measurement errors were below
      the known voxel size and clinically insignificant. No differences were found in
      the measurements from the 2 CBCT scan orientations of the skull. CONCLUSIONS:
      CBCT allows for clinically accurate and reliable 3-dimensional linear
      measurements of the craniofacial complex. Moreover, skull orientation during CBCT
      scanning does not affect the accuracy or the reliability of these measurements.

PMID- 19577145
TI  - Survival analyses of surgical miniscrews as orthodontic anchorage.
AB  - INTRODUCTION: The objectives of this study were to determine the survival rate of
      titanium surgical miniscrews and the clinical parameters that posed the highest
      risks for failure. METHODS: Ninety-seven titanium surgical miniscrews (diameter,
      1.2 mm; length, 8-12 mm) were placed in the maxilla of 49 patients, at either a
      high level (nonkeratinized area) or a medium level (mucogingival junction), with
      the 1-stage or the 2-stage surgical technique. Survival time, event of each screw
      (survival or failure), and 7 clinical parameters were gathered for survival
      analysis. Age and latency factors were analyzed with t tests. RESULTS: The
      cumulative survival rates were 85% at 6 months and 57% at 1 year. The Kaplan
      Meier log rank test indicated significant differences in 3 explanatory variables:
      surgical stage, level of placement, and tissue response. Cox proportional hazards
      regression indicated that the 2-stage surgical procedure had a higher risk than
      the 1 stage. Placement at the high level had a greater risk than placement at the
      medium level. Inflammatory hypertrophy tissue reaction showed a higher risk than
      normal or mild inflammation. The t test showed that age and latency period were
      not significant. CONCLUSIONS: Titanium surgical miniscrews can be satisfactorily
      used as orthodontic anchorage. Controlling some aspects of the surgical protocol
      could reduce the failure rate.

PMID- 19577143
TI  - Reliability and accuracy of cone-beam computed tomography dental measurements.
AB  - INTRODUCTION: Dental measurements are an integral part of the orthodontic records
      necessary for proper diagnosis and treatment planning. In this study, we
      investigated the reliability and accuracy of dental measurements made on cone
      beam computed tomography (CBCT) reconstructions. METHODS: Thirty human skulls
      were scanned with dental CBCT, and 3-dimensional reconstructions of the
      dentitions were generated. Ten measurements (overbite, overjet, maxillary and
      mandibular intermolar and intercanine widths, arch length available, and arch
      length required) were made directly on the dentitions of the skulls with a high
      precision digital caliper and on the digital reconstructions with commercially
      available software. Reliability and accuracy were assessed by using intraclass
      correlation and paired Student t tests. A P value of < or = 0.05 was used to
      assign statistical significance. RESULTS: Both the CBCT and the caliper
      measurements were highly reliable (r >0.90). The CBCT measurements tended to
      slightly underestimate the anatomic truth. This was statistically significant
      only for compounded measurements. CONCLUSIONS: Dental measurements from CBCT
      volumes can be used for quantitative analysis. With the CBCT images, we found a
      small systematic error, which became statistically significant only when
      combining several measurements. An adjustment for this error allows for improved
      accuracy.

PMID- 19577146
TI  - Condylar and ramal vertical asymmetry in unilateral and bilateral posterior
      crossbite patients and a normal occlusion sample.
AB  - INTRODUCTION: Our objective was to evaluate the condylar, ramal, and condylar
      plus-ramal mandibular vertical asymmetry in a group of adolescent subjects with
      normal occlusion and unilateral and bilateral posterior crossbite malocclusions.
      METHODS: Mandibular asymmetry index measurements (condylar, ramal, and condylar
      plus-ramal) were made on the panoramic radiographs of 126 subjects (51 boys, 75
      girls). The study groups consisted of 46 unilateral (19 boys, 27 girls; mean age,
      13.06 +/- 3.52 years) and 40 bilateral (16 boys, 24 girls; mean age, 12.72 +/-
      3.22 years) posterior crossbite patients and a group of 40 subjects (16 boys, 24
      girls; mean age, 14.43 +/- 3.05 years) with normal occlusion. One-way analysis of
      variance (ANOVA) was used to determine possible statistically significant
      differences between the groups for condylar, ramal, and condylar-plus-ramal
      asymmetry index measurements at the 95% confidence interval. RESULTS: No group
      showed statistically significant sex- or side-specific differences for posterior
      vertical height measurements (P > 0.05). Asymmetry indexes (condylar, ramal, and
      condylar-plus-ramal) were similar, and no statistically significant differences
      were found among the unilateral and bilateral posterior crossbite groups and the
      normal occlusion sample. CONCLUSIONS: No statistically significant sex- or side
      specific mandibular asymmetry was found among the 3 groups. Condylar asymmetry
      index values were significantly high compared with the 3% threshold value in each
      of the 3 groups, but comparisons between groups were not statistically
      significant.

PMID- 19577147
TI  - Mandibular incisor position changes in relation to amount of bite jumping during
      Herbst/multibracket appliance treatment: a radiographic-cephalometric study.
AB  - INTRODUCTION: The aim of this study was to analyze the effect of the cast
      Herbst/multibracket (MB) appliance on the position of the mandibular incisors in
      relation to the amount of mandibular advancement at the beginning of treatment.
      METHODS: We screened 133 patients with Class II Division 1 malocclusions. The
      subjects were divided into 3 bite-jumping groups: I, 49 subjects with bite
      jumping of <7 mm; II, 44 subjects with bite jumping of 7.5 to 9.5 mm; and III, 40
      subjects with bite jumping of >9.5 mm. Only group I with small (S) and group III
      with large (L) bite jumping were considered. The average ages of the subjects in
      the 2 bite-jumping groups were 13.6 +/- 2.4 years in the S group and 14.7 +/- 4.7
      years in the L group. The average treatment time with the Herbst/MB appliance was
      19 months. Lateral headfilms were evaluated at 3 times: before Herbst treatment,
      after Herbst treatment, and after MB treatment. RESULTS: During the Herbst phase,
      the mandibular incisors were significantly intruded, protruded, and proclined in
      both bite-jumping groups. Larger tooth movements occurred in group L than in
      group S. During the MB phase, comparable relapsing incisor tooth movements were
      seen in the 2 bite-jumping groups. There was moderate correlation between bite
      jumping and incisor position changes during the Herbst and the Herbst/MB
      treatment periods. No associations were found between the amount of bite jumping
      and the changes of sagittal and vertical jaw relationships, age, and treatment
      growth period. CONCLUSIONS: During the Herbst treatment period, there was an
      association between bite jumping and movement of the mandibular incisors: the
      greater the bite jumping, the larger the intrusion, protrusion, and proclination
      of teeth. During the MB treatment period, relapsing incisor tooth movements
      occurred that were independent of the original amount of bite jumping.

PMID- 19577148
TI  - A nonradiographic approach to detect Class III skeletal discrepancies.
AB  - INTRODUCTION: Because of the hereditary nature of Class III malocclusion,
      relatives of affected subjects often ask for a consultation. To estimate the
      degree of skeletal manifestation without exposing them to radiation, an
      alternative to lateral cephalograms would be valuable for preliminary diagnosis.
      Thus, we aimed to assess the validity of profile photographs to detect skeletal
      Class III discrepancy. METHODS: Profile photographs and lateral cephalograms were
      available from 42 young white men, 29 with Class III malocclusion and 13 with
      Class I. A computer-based analysis was performed including hard-tissue variables
      on cephalograms and soft-tissue variables on photographs RESULTS: Soft-tissue
      facial characteristics showed strong correlations with several skeletal
      structures of skeletal Class III subjects (r > or = 0.7, P < 0.001). Thus, soft
      tissue A'N'B', A'N'Pog', and N'A'/A'Pog' were highly related to skeletal ANB,
      ANPog, and NA/APog. Vertically, soft- and hard-tissue lower anterior face heights
      were strongly correlated. A soft-tissue A'N'B' angle of 6 degrees is the critical
      value below which skeletal Class III can be implied (sensitivity, 90.5%;
      specificity, 81.0%). This finding was validated among female subjects.
      CONCLUSIONS: A profile photograph can show with high probability a skeletal Class
      III discrepancy and might be useful for diagnosis during the initial
      consultation.

PMID- 19577149
TI  - Relationship between blood-spot insulin-like growth factor 1 levels and hand
      wrist assessment of skeletal maturity.
AB  - INTRODUCTION: Accurate prediction of the timing of the pubertal growth spurt and
      the amount of remaining growth are factors that affect treatment decisions in
      orthodontics, orthognathic surgery, and dental implantology. For many years,
      medical and dental professionals have considered hand-wrist radiographs the
      method of choice for the assessment of skeletal maturity. Insulin-like growth
      factor 1 (IGF-1) mirrors growth hormone levels and is used by endocrinologists to
      diagnose growth hormone disturbances. METHODS: The objective of this study was to
      establish a relationship between IGF-1 levels collected from blood-spot samples
      and hand-wrist radiographs at various skeletal stages. Eighty-four subjects (45
      female, 39 male) between the ages of 5 and 25 were included in the study. Each
      subject had personal information, a hand-wrist radiograph, and a blood-spot
      sample collected on the same day. RESULTS: The IGF-1 levels were highest at the
      hand-wrist skeletal stages that were previously associated with the greatest
      amount of mandibular growth. These levels were significantly higher than at
      prepubertal and postpubertal stages. In the postpubertal group, the IGF-1 levels
      were lower as the subjects' ages increased and they moved away from the onset of
      puberty. CONCLUSIONS: Longitudinal data are necessary to confirm the usefulness
      of this technique in predicting the timing, the intensity, and the end of the
      growth spurt.

PMID- 19577150
TI  - Comparison of arch dimension changes in 1-phase vs 2-phase treatment of Class II
      malocclusion.
AB  - INTRODUCTION: We compared arch dimension changes in 1-phase and 2-phase treatment
      of Class II malocclusion. This was a prospective randomized clinical trial
      conducted in the Department of Orthodontics at the University of Florida between
      1990 and 2003. METHODS: During phase 1 treatment, 86 subjects were treated with a
      bionator, 93 were treated with headgear/biteplane, and 81 served as the
      observation group. For phase 2, all subjects were then treated with full
      orthodontic appliances. Arch dimensions were followed; maxillary and mandibular
      alginate impressions were taken at baseline, end of early Class II treatment or
      observation, beginning of fixed appliance treatment, end of orthodontic
      treatment, and approximately 3 years posttreatment. Alginate impressions were
      taken of each dental arch at each data collection point. These were poured in
      orthodontic stone, trimmed, and photocopied from the occlusal aspect. These
      images were then scanned and measured. RESULTS: Although differences between the
      treatment groups were found in both the maxillary and mandibular arches after
      phase 1, these differences were no longer evident by the end of full orthodontic
      treatment or after posttreatment retention. CONCLUSIONS: There were no
      differences in arch dimensions after 1-phase or 2-phase treatment of Class II
      malocclusion.

PMID- 19577151
TI  - Early tooth movement with a clear plastic appliance in rats.
AB  - INTRODUCTION: In this preliminary study, we investigated early histologic changes
      of paradental tissues in response to a clear plastic appliance in rats. METHODS:
      Fifteen rats were divided into 3 groups. Group I was the untreated controls;
      group II received a clear plastic appliance made from a model, with the maxillary
      left first molar repositioned mesially 0.5 mm from the origin; and group III had
      a closed-coil spring to move the molar mesially. Specimens were prepared in
      parasagittal sections, and changes in paradental tissues were evaluated on days
      1, 4, and 7 by light microscopy. RESULTS: In group II, the periodontal ligament
      (PDL) was compressed in the bifurcation and apical areas of the roots of the
      molar. On day 7, the PDL of the apical and distal aspects of the roots and the
      bifurcation area showed further compression, with the PDL of the roots stretched
      along the mesial side. In group III, a disorganized and compressed PDL in the
      mesial cervical half and interradicular septum was observed, and the stretched
      fibers were at the distal aspects of the roots after days 4 to 7. CONCLUSIONS:
      Early histologic changes in response to the clear plastic appliance were
      intrusion and distal tipping despite the intended mesial movement. In this rat
      model, the observed histologic changes were subject to the direction and
      magnitude of forces generated by the clear aligner.

PMID- 19577152
TI  - Storage media effect on bond strength of orthodontic brackets.
AB  - INTRODUCTION: In testing bond strengths, various storage media are used. The
      purpose of this study was to determine the effect of 6 storage media and rinsing
      on the shear bond strength of bonded orthodontic brackets. METHODS: Bovine teeth
      were stored in 6 storage media for 7 months before bonding: dry (no medium),
      filtered water, 10% formalin, 1% chloramine T, 10% chloramine T, isotonic saline
      solution, and 70% ethanol. These teeth were further subdivided into 2 groups; 1
      group was rinsed with oil-free air and water spray before bonding orthodontic
      brackets, and the other group not rinsed. All specimens were tested in the shear
      peel mode to failure. RESULTS: The 10% formalin rinsed sample had statistically
      significantly higher bond strength (16.9 +/- 6.56 MPa), and storage in ethanol
      (rinsed, 9.04 +/- 5.61 MPa; not rinsed, 9.08 +/- 3.5 MPa) and dry (8.34 +/- 3.80
      MPa) produced significantly lower bond strengths. No difference was found between
      the other modes of storage or rinsing. The adhesive remnant index values showed
      no statistically significant difference between any groups. CONCLUSIONS: For bond
      strength studies, storage media can have an effect on bond strength results. Dry,
      formalin, and ethanol storage should be avoided. Water, isotonic saline solution,
      and chloramine T storage produced comparable bond strengths. Rinsing or not
      rinsing had no effect on bond strength with these storage media.

PMID- 19577153
TI  - Changes over time in canine retraction: an implant study.
AB  - INTRODUCTION: The objective of this study was to analyze rates of canine movement
      over the first 2 months of continuous retraction, when rate changes are expected.
      METHODS: Ten patients with bone markers placed in the maxilla and the mandible
      had their canines retracted over a 2-month period. Retraction was accomplished
      with beta-titanium alloy T-loop springs. Standardized 45 degrees oblique
      cephalograms where taken initially and every 28 days thereafter. The radiographs
      were scanned and digitized twice (the average was used for the analyses). The
      radiographs were superimposed by using the bone markers and oriented on the
      functional occlusal plane. Paired t tests were used to compare side and jaw
      effects. RESULTS: There were no significant differences between sides. The
      maxillary cusp was retracted 3.2 mm, with less movement during the first (1.1 mm)
      than during the second 4 weeks (2.1 mm). The maxillary apices did not move
      horizontally. There were no significant vertical movements in the cusps and
      apices of the maxillary canines. The mandibular cusp was retracted 3.8 mm-1.1 mm
      during the first and 2.7 mm during the second 4 weeks. The mandibular apices were
      protracted 1.1 mm. The cusps and apices were intruded 0.6 and 0.7 mm,
      respectively. The only difference between jaws was the greater protraction of the
      mandibular apices during the second 4 weeks and in overall movement. CONCLUSIONS:
      The rate of canine cusp retraction was greater during the second than the first 4
      weeks. The mandibular canines were retracted by uncontrolled tipping whereas the
      maxillary canines were retracted by controlled tipping.

PMID- 19577154
TI  - Superimposition of 3-dimensional cone-beam computed tomography models of growing
      patients.
AB  - INTRODUCTION: The objective of this study was to evaluate a new method for
      superimposition of 3-dimensional (3D) models of growing subjects. METHODS: Cone
      beam computed tomography scans were taken before and after Class III malocclusion
      orthopedic treatment with miniplates. Three observers independently constructed
      18 3D virtual surface models from cone-beam computed tomography scans of 3
      patients. Separate 3D models were constructed for soft-tissue, cranial base,
      maxillary, and mandibular surfaces. The anterior cranial fossa was used to
      register the 3D models of before and after treatment (about 1 year of follow-up).
      RESULTS: Three-dimensional overlays of superimposed models and 3D color-coded
      displacement maps allowed visual and quantitative assessment of growth and
      treatment changes. The range of interobserver errors for each anatomic region was
      0.4 mm for the zygomatic process of maxilla, chin, condyles, posterior border of
      the rami, and lower border of the mandible, and 0.5 mm for the anterior maxilla
      soft-tissue upper lip. CONCLUSIONS: Our results suggest that this method is a
      valid and reproducible assessment of treatment outcomes for growing subjects.
      This technique can be used to identify maxillary and mandibular positional
      changes and bone remodeling relative to the anterior cranial fossa.

PMID- 19577156
TI  - Quantitative investigation of palatal bone depth and cortical bone thickness for
      mini-implant placement in adults.
AB  - INTRODUCTION: Cortical bone thickness and overall bone depth are important
      factors to consider when placing an orthodontic mini-implant. The purpose of this
      study was to investigate both variables in the palate quantitatively to aid
      clinicians in planning successful mini-implant placements. METHODS: Thirty dry
      skulls were imaged with cone-beam computed tomography technology. Coronal slices
      were generated on which overall bone depth and cortical bone thickness were
      measured at 4 levels and 34 palatal placement sites. One-way analysis of variance
      (ANOVA) was used for data analysis. RESULTS: Overall bone depth decreased with
      increasing distance from the midsagittal plane and from the anterior to the
      posterior palatal regions. Cortical bone thickness decreased from anterior to
      posterior, but no differences were detectable within measurement levels.
      CONCLUSIONS: Bone depth and cortical bone thickness of the palate were most
      favorable for temporary anchorage device placement at the level of the first and
      second premolars. This information could aid clinicians in choosing suitable
      palatal placement sites for orthodontic mini-implants.

PMID- 19577155
TI  - Cytotoxicity and estrogenicity of Invisalign appliances.
AB  - INTRODUCTION: Our purpose was to study the in-vitro cytotoxic and estrogenic
      properties of Invisalign appliances (Align Technology, Santa Clara, Calif).
      METHODS: Three sets, each consisting of a maxillary and a mandibular appliance,
      of as-received aligners were immersed in normal saline solution for 2 months.
      Samples of eluents were diluted to 3 concentrations (5%, 10%, and 20% vol/vol)
      and tested for cytotoxicity on human gingival fibroblasts and estrogenicity by
      measuring their effect on the proliferation of the estrogen-responsive MCF-7
      breast cancer cells. All assays were repeated 4 times for each maxillary and
      mandibular set, and the results were analyzed with 2-way analysis of variance
      (ANOVA) with appliance and concentration serving as predictors at the .05 level
      of significance; differences among groups were investigated with the Tukey test.
      RESULTS: There was no evidence of cytotoxicity on human gingival fibroblasts and
      no stimulation of proliferation of the MCF-7 cell line at any concentration,
      indicating no estrogenicity of aligner eluents. CONCLUSIONS: The use of
      Invisalign appliances did not seem to induce estrogenic effects under the
      conditions of this experiment.

PMID- 19577158
TI  - Orthodontic correction of a maxillary canine-first premolar transposition.
AB  - Transposition is a form of ectopia, in which 2 adjacent teeth change positions in
      the dental arch or 1 tooth develops in a position occupied by a nonadjacent
      tooth. Transposition can be partial or complete. Despite their low prevalence in
      the general population, transpositions are a challenge to orthodontists,
      especially if treatment aims to correct the order of the teeth. This article
      reports the diagnosis, planning, and treatment of a unilateral maxillary canine
      first premolar transposition in a female patient treated orthodontically without
      premolar extraction and with correction of the transposition. Treatment options,
      advantages and disadvantages of each method, and the mechanics used during the
      treatment are also discussed.

PMID- 19577157
TI  - Orthodontic distalization with rigid plate fixation for anchorage after bone
      grafting and maxillary sinus lifting.
AB  - A 68-year-old woman was treated with an autogenous particulated bone graft from
      the anterior part of the mandible to elevate the right maxillary sinus floor,
      which was next to the alveolar ridge of an edentulous area, to facilitate dental
      implant placement. A rigid plate for anchorage was placed into the zygomatic
      bone. The maxillary right canine and the premolars were moved distally 6 months
      after the implant was placed and osteointegration of the bone graft had occurred.
      The Class II relationship was corrected. After tooth movement, the patient
      underwent multislice computed tomography to determine the mineral density of the
      bone graft and compare it with the opposite side of the maxilla. The mineral
      density showed values above normal for the posterior segment of the maxilla.
      Although the patient was taking bisphosphonate for treatment of osteoporosis, no
      related complications were noted during treatment.

PMID- 19577159
TI  - Intramaxillary and intermaxillary absolute anchorage with an endosseous dental
      implant and rare-earth magnets.
AB  - This case report describes the management of a partially edentulous adult with a
      severe deepbite malocclusion and a collapsed buccal segment because of
      supraeruption of the maxillary second and third molars. The treatment involved
      placement of an endosseous dental implant to achieve absolute intermaxillary and
      intramaxillary anchorage. Rare-earth magnets embedded in acrylic bite-blocks were
      used to intrude the supraerupted maxillary molars on the right side. After use as
      an anchorage device, the implant was restored and brought into occlusion. Good
      occlusal and esthetic results were achieved with this cost-effective treatment.

PMID- 19577160
TI  - Evaluation of the radiographic cephalometry learning process by a learning
      virtual object.
AB  - INTRODUCTION: Radiographic cephalometry is a complex area of study. The
      literature shows a lack of interobserver reproducibility in the definition and
      identification of cephalometric landmarks. The aim of this study was to test a
      learning virtual object (LVO) called ceph learning used in the teaching of
      radiographic cephalometry and to verify whether it improves performance of the
      landmarking process. METHODS: A total of 40 undergraduate students were divided
      into 2 groups. Group A was taught according to the conventional teaching method
      of theory and practical classes, and group B was taught with an LVO. The
      students' learning performance was tested by using a multiple-choice
      questionnaire that covered the knowledge and understanding of cephalometry and by
      the index of correct landmark identification. The Student t test was used to
      check statistical differences between the 2 groups. LVO usability was evaluated
      with a questionnaire based on the system usability scale. RESULTS: In the first
      posttest, the Student t test showed no significant differences (P >0.05).
      However, in the second posttest 15 days later, a decrease was observed in the
      scores of group A, with significant differences (P <0.05). Students approved the
      LVO usability aspects--effectiveness, efficiency, and satisfaction (82.45% +/-
      6.78%). CONCLUSIONS: LVO was shown to be a useful and efficient tool in the
      learning process and might assist the learning of cephalometry.

PMID- 19577161
TI  - Neoplastic hematopathology. Preface.

PMID- 19577162
TI  - Acute myeloid leukemia.
AB  - The evolution of acute myeloid leukemia (AML) classification reflects greater
      understanding of the AML pathogenesis. The 2008 World Health Organization
      classification incorporated cytogenetic and molecular genetic findings and
      introduced important prognostic correlations. In this article, the authors
      discuss the different types of AML and their diagnoses.

PMID- 19577163
TI  - Acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia and lymphoblastic lymphoma constitute a family of
      genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid
      progenitors. Diagnosis is based on morphologic, immunophenotypic, and genetic
      features that allow differentiation from normal progenitors and other
      hematopoietic and nonhematopoietic neoplasms. Current intensive chemotherapy
      regimens have accomplished overall cure rates of 85% to 90% in children and 40%
      to 50% in adults, with outcomes depending on the genetic subtype of disease and
      clinical features at presentation. Therapy is optimized using minimal residual
      disease studies that employ flow cytometric and molecular methodologies, and are
      important determinants of prognosis. Genetic analyses currently underway are
      likely to provide insight into biology, mechanisms of relapse, pharmacogenetics,
      and new potential therapeutic targets, which should aid in further improvement of
      outcome in this disease.

PMID- 19577164
TI  - The myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow
      disorders that affect mostly the elderly and have a variable probability of
      progression to acute leukemia. The diagnosis of MDS rests largely on a critical
      morphologic review of blood and bone marrow slides, with careful correlation with
      other clinical and essential laboratory data, including cytogenetics. This
      article discusses the epidemiology and clinical and pathologic features of MDS
      and pertinent diagnostic and prognostic classifications, with a brief overview of
      treatment options. Other considerations in the differential diagnosis are also
      briefly outlined.

PMID- 19577165
TI  - The myeloproliferative neoplasms: insights into molecular pathogenesis and
      changes in WHO classification and criteria for diagnosis.
AB  - In the 2008 World Health Organization-sponsored classification of hematopoietic
      and lymphoid malignancies, changes were made in the classification and criteria
      for the diagnosis of some of the myeloproliferative disorders. These changes were
      initiated by recent insights into the molecular pathogenesis of these disorders.
      In this article, the changes made to the myeloproliferative neoplasm and the
      basis of the new classification and altered diagnostic criteria are summarized
      and discussed.

PMID- 19577166
TI  - Plasma cell myeloma.
AB  - Plasma cell myeloma is a heterogenous disease with variable clinical presentation
      and outcome. The prognosis is largely determined by tumor biology. Newer
      therapeutic agents are rapidly changing the survival outlook of myeloma patients.

PMID- 19577167
TI  - Atypical lymphoid hyperplasia mimicking lymphoma.
AB  - The distinction between reactive and neoplastic lymphoid infiltrates is a common
      problem in clinical practice and can be problematic. The clinical implications
      for both the patient and the treating clinician are profound. In this article, we
      discuss six of the common entities that can present as atypical lymphoid
      hyperplasia and thus can mimic malignant lymphomas, with emphasis on morphologic
      features, immunophenotypic findings, and molecular correlates that help
      distinguish these disorders from neoplastic conditions. The six conditions to be
      discussed in detail include reactive follicular hyperplasia versus follicular
      lymphoma; progressive transformation of germinal centers versus nodular
      lymphocyte predominant Hodgkin lymphoma; immunoblastic proliferations versus
      diffuse large B-cell lymphomas; variant forms of Castleman disease that may mimic
      a number of lymphoid cancers; Kikuchi's disease versus large cell lymphomas; and
      finally, dermatopathic lymphadenopathy and its distinction from lymph nodes
      showing early involvement by cutaneous T-cell lymphoma (Mycosis fungoides).

PMID- 19577168
TI  - Hodgkin lymphoma.
AB  - Hodgkin disease was first described more than 175 years ago. Clinically and
      histomorphologically, the features of Hodgkin lymphoma are unusual for a lymphoma
      or for other malignancies. The incidence of Hodgkin lymphoma is estimated to be
      7400 new cases per year in the United States, resulting in an age-adjusted yearly
      rate of 2.7 per 100,000 per year. There have been numerous classifications of non
      Hodgkin lymphoma over the years, but the organizational schemes of Hodgkin
      lymphoma have been stable. This article reviews the diagnosis of the various
      types of Hodgkin lymphoma classification, diagnosis and differential.

PMID- 19577169
TI  - Indolent lymphomas of mature B lymphocytes.
AB  - The lymphomas of small B lymphocytes are a biologically diverse group of B cell
      derived neoplasms that includes B cell small lymphocytic lymphoma/chronic
      lymphocytic leukemia; mantle cell lymphoma; follicular lymphoma; nodal, splenic
      and extranodal marginal zone lymphomas; and lymphoplasmacytic lymphoma. They are
      distinguished from one another on clinical, morphological, phenotypic and genetic
      grounds. This article reviews the essential diagnostic and biologic features of
      these clinically indolent B cell malignancies.

PMID- 19577170
TI  - Diffuse large B-cell lymphomas and burkitt lymphoma.
AB  - Diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphoma (BL) account for the
      majority of aggressive lymphomas in adults and children. DLBCLs exhibit marked
      biological heterogeneity and variable clinical presentation and clinical course.
      Conversely, BL is genetically relatively homogeneous but associated with variable
      clinicopathological features. In this article, the authors summarize the recent
      advances pertaining to these B-cell neoplasms, following the latest World Health
      Organization classification and focusing on changes introduced since the previous
      edition. These changes include the addition of variants and subgroups of DLBCLs
      and "borderline" categories for high-grade B-cell neoplasms that show features
      intermediate between DLBCL and classical Hodgkin lymphoma, or between DLBCL and
      BL. In particular, the diagnostic and therapeutic problems related to neoplasms
      with features intermediate between DLBCL and BL will be discussed.

PMID- 19577171
TI  - Peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are malignancies of immunologically mature T
      cells that arise in peripheral lymphoid tissues such as lymph nodes, spleen,
      gastrointestinal tract, and skin. These lymphomas are uncommon as compared with
      the incidence of B-cell lymphomas, and they comprise only 5% to 10% of non
      Hodgkin lymphomas in North America and Western Europe. A variety of specific
      disease entities have been recognized among PTCLs, and they tend to have lymph
      node, extranodal/cutaneous, or mixed leukemic/lymphomatous presentations. Most
      PTCLs have an aggressive clinical course. The clinicopathologic features of the
      various PTCLs are described herein.

PMID- 19577172
TI  - The leukemias of mature lymphocytes.
AB  - The leukemias of mature B cells and T cells are a limited set of diseases in
      which blood and bone marrow are the primary sites of involvement. Although they
      may superficially resemble one another, they have distinct clinical and
      pathologic features and must be distinguished from one another. In this article,
      the major clinical, morphologic, phenotypic, and molecular genetic features of
      the mature B- and T-cell leukemias are reviewed, and differential diagnostic
      considerations are discussed.

PMID- 19577173
TI  - Bone marrow involvement by hodgkin and non-hodgkin lymphomas.
AB  - Bone marrow evaluation plays a critical role in staging and predicting prognosis
      in patients with Hodgkin lymphoma or non-Hodgkin lymphoma. Bone marrow can be the
      initial site of detection of lymphoma in patients with unexplained symptoms or
      cytopenias. A comprehensive evaluation of bone marrow includes complete blood
      counts, blood morphology, bone marrow aspirate, and generous core biopsy
      sections. Specialized testing should be used in a logical fashion on a case by
      case basis.

PMID- 19577174
TI  - Molecular diagnosis of hematopoietic and lymphoid neoplasms.
AB  - This chapter summarizes the significance and molecular diagnostic detection of
      genetic abnormalities commonly associated with hematolymphoid neoplasms.
      Methodologic aspects of laboratory diagnosis are presented, as well as discussion
      of multiparameter genotyping of tumors for prognosis and the role of minimal
      residual disease monitoring in specific neoplasms.

PMID- 19577175
TI  - Lip augmentation and rejuvenation using Dermicol-P35 30G: personal experiences
      from my clinic.
AB  - Predictable changes in the lips caused by aging often prompt women to seek lip
      augmentation and/or rejuvenation. This article describes the clinical experience
      of patients who underwent lip augmentation and rejuvenation procedures using
      Dermicol-P35 30G (Evolence Breeze; Ortho Dermatologics, Skillman, NJ) a novel, D
      ribose cross-linked, porcine collagen dermal filler. The majority of patients
      reported that the improvement afforded by Dermicol-P35 30G was either good or
      very good 3 months after their procedure, with minimal adverse effects.

PMID- 19577176
TI  - Repair of acne scars with Dermicol-P35.
AB  - Acne vulgaris is a prevalent skin condition that can cause disfiguring residual
      scarring. While the complete removal of acne scars is unlikely, several
      treatments exist that can improve the appearance of acne scars. Dermal fillers
      offer a simple, nonsurgical corrective procedure that can provide improved skin
      texture. Dermicol-P35 (Evolence [Ortho Dermatologics, Skillman, NJ]) is a new,
      highly purified, ribose cross-linked, porcine collagen-based dermal filler that
      has demonstrated low immunogenicity and results that persist for at least 12
      months. This article presents the aesthetic results of a male patient treated
      with Dermicol-P35 for severe facial acne scars.

PMID- 19577177
TI  - Nonsurgical hand rejuvenation with Dermicol-P35 30G.
AB  - Aesthetic hand rejuvenation and restoration have been relatively overlooked
      compared with other aesthetic enhancements. Cosmetic dermal fillers provide
      physicians and patients with a nonsurgical option for restoring volume and a
      youthful appearance to the aging and damaged hand. This paper presents the
      clinical experience of patients who received Dermicol-P35 30G (Evolence Breeze;
      Ortho Dermatologics, Skillman, NJ) injection for rejuvenation and restoration of
      the hand.

PMID- 19577179
TI  - The science and technology of Dermicol-P35: utility and safety in aesthetic
      procedures. Introduction.

PMID- 19577178
TI  - The use of Dermicol-P35 dermal filler for nonsurgical rhinoplasty.
AB  - A growing number of patients with congenital or acquired nasal defects is seeking
      nonsurgical procedures to correct the appearance of their nose. The use of
      fillers for the correction of nasal deformities is expanding because of their low
      risk and reversibility compared with surgery. Dermicol-P35 (Evolence; Ortho
      Dermatologics, Skillman, NJ) is a novel crosslinked, fibrillar type I collagen
      isolated from porcine tendons that has not been associated with the same degree
      of immunogenicity as bovine collagen. The use of Dermicol-P35 in this study of 12
      subjects was associated with high tolerance, as well as a high degree of
      satisfaction.

PMID- 19577182
TI  - [The Antoine-Beclere medal. Editorial].

PMID- 19577180
TI  - Cheek augmentation with Dermicol-P35 27G.
AB  - Full and high cheekbones are considered a desirable component of facial
      attractiveness. The aging process can result in a loss of facial volume and
      changes in facial contours. Cheek augmentation can replace lost facial volume,
      rejuvenate facial appearance, enhance cheek prominence, and improve facial
      symmetry. A new, highly purified, porcine-based collagen filler Dermicol-P35 #27G
      (Evolence; Ortho Dermatologics, Skillman, NJ) is now available that does not
      require pretreatment sensitivity testing and has shown a 12-month persistence of
      results in clinical trials. This article discusses the clinical experience of
      patients who received cheek augmentation with Dermicol-P35.

PMID- 19577181
TI  - Correction of tear trough deformity with novel porcine collagen dermal filler
      (Dermicol-P35).
AB  - Deformity of the tear trough region, which can occur during the aging process,
      can result in dark shadows under the eyes and a fatigued appearance. Augmentation
      of the tear trough is challenging because of the thin skin and lack of fat in the
      region. Adding volume to the tear trough region with a dermal filler is a
      nonsurgical procedure with minimal discomfort to the patient. Dermicol-P35
      (Evolence; Ortho Dermatologics, Skillman, NJ) is a new, ribose crosslinked,
      highly purified, porcine-based collagen filler that does not require prior skin
      testing and has shown improved persistence compared with bovine collagen-based
      dermal fillers. In this article, we present the clinical outcomes of patients who
      have received treatment with a novel ribose crosslinked porcine collagen dermal
      filler for the correction of tear trough deformity.

PMID- 19577183
TI  - Methods for energizing cell-free protein synthesis.
AB  - The productivity of cell-free protein synthesis depends critically upon the
      efficiency of ATP regeneration. In addition, the expensive energy sources used in
      the conventional cell-free protein synthesis systems account for the major part
      of the overall cost for the expression of proteins. Therefore, it is essential to
      implement a cheaper and more efficient ATP regeneration method in order to make
      cell-free protein synthesis a viable option for industrial protein production. In
      this article, we review the recent progress in the methodologies for supplying
      ATP during cell-free protein synthesis in E. coli extracts.

PMID- 19577184
TI  - Expression and purification of soluble HIV-1 envelope glycoprotein gp160 mutant
      from Saccharomyces cerevisiae.
AB  - Here we report the expression of HIV-1 gp160 and its mutated proteins in
      Saccharomyces cerevisiae. Two strong hydrophobic regions, aa 511-537 and aa 679
      703, were predicted by GCG Wisconsin Package software and removed to investigate
      the solubility of the mutated gp160 (gp160Delta12). The results showed that
      gp160Delta12 assumes high solubility as to be present in supernatant of cell
      lysate exclusively. The mutant exists as trimeric form in solutions via some
      inter-molecule disulfide bonds, which can be associated to monomer with the
      reduced reaction of DTT. The fermentation procedure was optimized to get high
      cell density yield and expression level as approximately 10 mg/L. After
      purification with electro elution, gp160Delta12 was checked as glycosylation form
      by Endo-H deglycosylating catalysis. The ELISA performed with a panel of human
      sera suggests that the purified gp160Delta12 shares some determinants with gp120
      and gp41, but exposes some distinct epitopes that react with early HIV-infected
      antibody. Thus, we may provide a novel antigen for immunodetection assay, vaccine
      candidate, and other relative research purposes.

PMID- 19577185
TI  - Determination of the in vivo distribution of nuclear matrix attachment regions
      using a polymerase chain reaction-based assay in Arabidopsis thaliana.
AB  - Matrix attachment regions (MARs) are the regions on genomic DNA that are attached
      to the nuclear matrix in eukaryotes. Previous in vitro and in silico MAR analyses
      have shown that MARs distribute at average intervals of about 5 kb on the
      Arabidopsis thaliana genome. However, the in vivo evidence for the distribution
      of MARs in A. thaliana is lacking. Therefore, we have used a polymerase chain
      reaction (PCR)-based method to investigate the in vivo locations of MARs across
      an 80 kb region of A. thaliana genome. This assay indicated that the average
      interval of MARs within this region is 4.7 kb (range 1 to 11 kb), well consistent
      with the previous in vitro and in silico MAR studies. This result suggests that
      average size of the chromatin loop in A. thaliana is smaller when compared with
      the other eukaryotes, in which the sizes are known to vary in the range from 9 to
      100 kb. However, we found that the number of genes per chromatin loop (1-3 genes)
      in A. thaliana is similar to those found in other eukaryotes. Furthermore, as in
      animals' MARs, DNase I hypersensitive sites were also found in the MARs end
      region in A. thaliana. Our results suggest that basic organization of chromatin
      loop in A. thaliana is similar to other eukaryotes in the view that it contains a
      few genes, and that the average size of chromatin loop in eukaryotes is possibly
      determined by genome structure, such as gene density and average gene size.

PMID- 19577186
TI  - Effects of non-B DNA sequences on transgene expression.
AB  - DNA conformation may be an important factor affecting gene transcription. In this
      study, we examined how DNA sequences with unusual conformations affect transgene
      expression. A(30) and (CG)(15) sequences that can adopt the B' and Z
      conformations, respectively, were introduced into a beta-actin promoter.
      Luciferase plasmids containing the manipulated promoter were transfected into
      NIH3T3 cells by electroporation and were delivered into mouse livers with a
      hydrodynamics-based injection. Expression from plasmid with the (CG)(15) sequence
      was multiple times higher than expression from control plasmid DNA. The A(30)
      sequence also tended to enhance expression. These results suggest that non-B DNA
      sequences could improve transgene expression in cells.

PMID- 19577187
TI  - Cloning and expression of GH11 xylanase gene from Aspergillus fumigatus MKU1 in
      Pichia pastoris.
AB  - A xylanase gene, xynf11a of Aspergillus fumigatus MKU1 was cloned and expressed
      in Pichia pastoris X33. Two exons of the xynf11a gene were amplified separately
      and fused by overlap extension PCR. The fused product was cloned in yeast
      expression vector pPICZB and expressed in P. pastoris under the control of the
      AOX1 promoter. P. pastoris transformants expressing recombinant xylanases were
      selected on xylan agar plate and their ability to produce the xylanase was
      evaluated in flask cultures. P. pastoris X33 (pZBxynf11aFP) efficiently secreted
      the recombinant xylanase into the medium and produced the high level of xylanase
      activity (14 U/ml) after 96 h of growth. The recombinant xylanase produced by P.
      pastoris showed maximum activity at pH 6.0 and temperature 60 degrees C. The
      recombinant xylanase did not exhibit any cellulase activity and hence it could be
      potentially used for pretreatment of paper pulp before bleaching.

PMID- 19577188
TI  - Multiple inhibitory factor removal from an Escherichia coli cell extract improves
      cell-free protein synthesis.
AB  - Cell-free protein synthesis systems are generally influenced by the nature of the
      cell extract, which contains various factors on the chromosomal DNA. Some of the
      Escherichia coli cell extract factors are essential, despite their negative
      effects on protein synthesis, because they are required during the cell growth
      and/or extract preparation stage. In this study, modified E. coli strains were
      generated by inserting a streptavidin binding peptide (SBP) tag sequence at the
      3' termini of the genes encoding polynucleotide phosphorylase (PNPase) and/or
      Exodeoxyribonuclease V alpha chain (RecD) on the chromosomal DNA. The SBP-tagged
      target gene products were specifically removed from the cell extract prepared
      from modified E. coli cells using SBP affinity resin. The linear DNA-directed
      cell-free protein synthesis using the treated extract achieved higher
      productivity, especially when removing both the PNPase and RecD factors. Using
      this strategy to remove multiple inhibitory factors in a cell extract will be
      widely applicable to improve cell-free protein synthesis.

PMID- 19577189
TI  - Characterization of a recombinant beta-glucosidase from the thermophilic
      bacterium Caldicellulosiruptor saccharolyticus.
AB  - A recombinant beta-glucosidase from Caldicellulosiruptor saccharolyticus DSM 8903
      with a specific activity of 13 U/mg was purified by heat treatment and His-Trap
      affinity chromatography and identified as a single 54 kDa band on SDS-PAGE. The
      molecular mass of the native enzyme was 108 kDa as a dimer by gel filtration.
      beta-Glucosidase showed optimum activity at pH 5.5 and 70 degrees C for p
      nitrophenyl (pNP)-beta-d-glucopyranoside. The half-lives of the enzyme at 60, 70,
      and 80 degrees C were 250, 24.3, and 0.4 h, respectively. The enzyme exhibited
      catalytic efficiency and specific activity for pNP-beta-d-fucopyranoside, pNP
      beta-d-glucopyranoside, and pNP-beta-d-galactopyranoside in decreasing order
      among aryl-beta-glycosides, but not for aryl-alpha-glycosides. Cello
      oligosaccharides from n = 2 to 5 as substrates using 4 mM each sugar and 3 U/mg
      of enzyme were completely hydrolyzed to glucose at 70 degrees C within 16 h.

PMID- 19577190
TI  - Regioselective hydroxylation of isoflavones by Streptomyces avermitilis MA-4680.
AB  - Screening of bacterial whole cells was performed for regioselective hydroxylation
      of daidzein and genistein. Among the strains examined, Streptomyces avermitilis
      MA-4680 showed high ortho-dihydroxylation activity to produce 3',4',7
      trihydroxyisoflavone and 3',4',5,7-tetrahydroxyisoflavone from daidzein (4',7
      dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), respectively.
      Using 100 mg cells (wet wt.) and 1% (v/v) Triton X100 in 1 ml of total reaction
      volume, where 100 microl of the substrate solution (0.5 mM in 10% (v/v) mixed
      solvent of DMSO:MeOH = 3:7) was added to 900 microl of potassium phosphate buffer
      (100 mM, pH 7.2), a 16% molar conversion yield of 3',4',7-trihydroxyisoflavone
      was obtained from 0.5 mM daidzein after 24 h of reaction time at 28 degrees C and
      200 rpm. Ketoconazole significantly (ca. 90%) inhibited the ortho-hydroxylation
      activity of daidzein, suggesting that cytochrome P450 enzymes putatively play
      roles in regiospecific daidzein hydroxylation. The analysis of the reaction
      products was determined by gas chromatography/mass spectrometry (GC/MS) and (1)H
      NMR.

PMID- 19577191
TI  - beta-carotene production enhancement by UV-A radiation in Dunaliella bardawil
      cultivated in laboratory reactors.
AB  - beta-carotene is an antioxidant molecule of commercial value that can be
      naturally produced by certain microalgae that mostly belong to the genus
      Dunaliella. So far, nitrogen starvation has been the most efficient condition for
      enhancing beta-carotene accumulation in Dunaliella. However, while nitrogen
      starvation promotes beta-carotene accumulation, the cells become non-viable;
      consequently under such conditions, continuous beta-carotene production is
      limited to less than 1 week. In this study, the use of UV-A radiation as a tool
      to enhance long-term beta-carotene production in Dunaliella bardawil cultures was
      investigated. The effect of UV-A radiation (320-400 nm) added to
      photosynthetically active radiation (PAR, 400-700 nm) on growth and carotenoid
      accumulation of D. bardawil in a laboratory air-fluidized bed photobioreactor was
      studied. The results were compared with those from D. bardawil control cultures
      incubated with PAR only. The addition of 8.7 W.m(-2) UV-A radiation to 250 Wm(-2)
      PAR stimulated long-term growth of D. bardawil. Throughout the exponential growth
      period the UV-A irradiated cultures showed enhanced carotenoid accumulation,
      mostly as beta-carotene. After 24 days, the concentration of beta-carotene in UV
      A irradiated cultures was approximately two times that of control cultures.
      Analysis revealed that UV-A clearly induced major accumulation of all-trans beta
      carotene. In N-starved culture media, beta-carotene biosynthesis in UV-A
      irradiated cultures was stimulated. We conclude that the addition of UV-A to PAR
      enhances carotenoid production processes, specifically all-trans beta-carotene,
      in D. bardawil cells without negative effects on cell growth.

PMID- 19577192
TI  - Alkaline pH enhances farnesol production by Saccharomyces cerevisiae.
AB  - External environments affect prenyl alcohol production by squalene synthetase
      deficient mutant Saccharomyces cerevisiae ATCC 64031. Cultivation of the yeast in
      medium with an initial pH ranging from 7.0 to 8.0 increased the amount of
      secreted farnesol (FOH). In contrast, acidic medium with a pH below 4.0 increased
      the intracellular FOH and its isomer nerolidol. These effects of alkaline pH were
      also observed on constant pH cultivation in a jar fermenter. On cultivation for
      133 h, the FOH production reached 102.8 mg/l.

PMID- 19577193
TI  - Analysis of genes encoding the 2,4-dichlorophenoxyacetic acid-degrading enzyme
      from Sphingomonas agrestis 58-1.
AB  - A 2,4-dichlorophenoxy acetic acid (2,4-D)-degrading bacterium, strain 58-1, was
      newly isolated from soil samples collected in the Fukuoka Prefecture, Japan, and
      grown on an enrichment culture medium containing 2,4-D as the sole carbon source.
      Phylogenic analysis identified strain 58-1 as Sphingomonas agrestis. In 2,4-D
      degraders, classes I, II, and III inherit the tfdA, cadA, and tfdAalpha genes,
      respectively, and the results from degenerate-PCR indicated that this strain
      belongs to the class II degraders. A clone that includes the cadA gene homolog of
      S. agrestis 58-1 was screened from a library by using the PCR amplified fragment
      as a DNA probe. The cloned fragment was sequenced and found to consist of 5043
      nucleotides and include 3 open reading frames (orfs). The orf1, orf2, and orf3
      genes encode polypeptides consisting of 412, 448, and 177 amino acids,
      respectively. The Orf2 product shares a high degree of sequence similarity (92%)
      with the large subunit of 2,4-D oxygenase from the Bradyrhizobium sp. strain
      HW13, which belongs to the class III 2,4-D degraders, while the orf3 product
      shared 63% sequence similarity with the small subunit of 2,4-D oxygenase from the
      strain HW13. The results of the functional expression analysis using various
      deletion mutants in Escherichia coli revealed that the expression of both orf2
      and orf3 genes, but not orf1, is essential for the conversion of 2,4-D to 2,4
      DCP. From these results, we conclude the first isolation of 2,4-D oxygenase genes
      from a class II 2,4-D degrader.

PMID- 19577194
TI  - Sugar induces death of the bottom fermenting yeast Saccharomyces pastorianus.
AB  - We confirmed that sugar-induced cell death (SICD) occurs in the bottom fermenting
      yeast Saccharomyces pastorianus under anaerobic conditions and that mitochondrial
      DNA is only partly required for SICD. Fermentation tests using different ratios
      of glucose and non-glucose nutrients demonstrated that SICD is influenced by the
      balance between these nutrients.

PMID- 19577196
TI  - Comparative study of silk fibroin porous scaffolds derived from salt/water and
      sucrose/hexafluoroisopropanol in cartilage formation.
AB  - The purpose of this study is to create a new silk fibroin scaffold with
      sufficient three-dimensional morphology and porous structure for cartilage
      formation. We have applied sucrose particles sized around 300 to 500 microm as
      porogens compared to equal-sized salt particles. After the porogen was leached
      out with water, scaffolds were prepared with fibroin derived from
      sucrose/hexafluoroisopropanol (Su/H) or salt/water (Sa/W) based composites. A
      compression test indicated that the Sa/W fibroin was much harder than the Su/H
      fibroin, but a protease enzyme digested the Sa/W fibroin more quickly than Su/H
      fibroin. Rabbit ear chondrocytes were seeded onto the scaffolds for 4-8 week in
      vitro culture and histological analyses were performed. The distribution of
      cartilage formation in Safranin O staining was more homogenous in Su/H fibroin
      than that of Sa/W fibroin. The overall amount of cartilage was significantly
      better in the Su/H fibroin than that in the Sa/W fibroin. However, the inner
      structure of pore wall in the Sa/W fibroin was rough and microporous with
      cartilage matrix deposition, while that in the Su/H fibroin was thin and
      homogenous. Since mature cartilage gradually regenerates to fill the porous
      space, slowly degradable Su/H fibroin should be a better candidate for cartilage
      formation.

PMID- 19577195
TI  - Enhanced differentiation of mesenchymal stem cells into NP-like cells via 3D co
      culturing with mechanical stimulation.
AB  - This study proposes a three-dimensional co-culturing system of mesenchymal stem
      cells (MSCs) and nucleus pulposus (NP) cells from New Zealand white male rabbits
      to differentiate MSCs into NP-like cells. The preferable ratio of MSCs to NP
      cells and the effects of mechanical stimulation were investigated without
      biochemical reagents. The preferable ratio was investigated without mechanical
      stimulation using five groups: Group I (MSC control); Group II (NP cell control);
      and Groups III, IV, and V, for which the ratios of NP cells to MSCs were 1:1,
      1:2, and 2:1, respectively. During culture for 10 days without stimulation, the
      proliferation of MSCs did not increase after day 4. NP cells proliferated more
      when co-cultured as in Group V. However, the degree of differentiation of MSCs
      increased significantly in Group V. The differentiation of NP cells decreased
      gradually over time. When mechanical stimulation was applied to Groups I, II, and
      V, it contributed to the differentiation of MSCs into NP-like cells, as well as
      to that of NP cells, but did not contribute to the proliferation of either cell
      type. The contribution of mechanical stimulation to differentiation was also
      confirmed by RT-PCR.

PMID- 19577197
TI  - Directional migration of neuronal PC12 cells in a ratchet wheel shaped
      microchamber.
AB  - Directional migration of neuronal cells over long distances is critical for the
      developing and regenerating nervous system. A scaffold, which includes radial
      glia, provides a route between the germinal zone and the destination, with the
      direction of migration being attributed mainly to chemotaxis. However, the
      decrease in chemokine concentration with distance complicates cell guidance
      control over long distances. Our working hypothesis is that neuronal cells
      migrate directionally on an anisotropic and periodic scaffold. We tested this in
      a model involving neuronal PC12 cells cultured in a ratchet wheel-shaped
      microchamber. The microchamber was constructed by printing a patterned, thin film
      of polydimethylsiloxane (PDMS), to which the cells adhere weakly, onto a collagen
      coated dish, to which the cells adhere strongly, using a microcontact printing
      technique. The cells can attach, extend neurites, and migrate on the anisotropic
      and periodic collagen-coated area between the ratchet wheel-shaped outer frame
      and round inner frame of the PDMS. We found that the microchamber geometry
      affected the direction of migration, even though the mean length of the longest
      neurite was independent of microchamber geometry. The time-course trace of cell
      body migration and neurite tips showed that the neurite tips remained around the
      tips of the ratchet teeth. These results suggested that neuronal cells migrate
      directionally on a scaffold, even in the absence of chemokine, and reveal a new
      conceptual framework for neuronal migration.

PMID- 19577198
TI  - Protection of vulnerable adults.

PMID- 19577199
TI  - Safeguarding vulnerable adults in the emergency department.

PMID- 19577200
TI  - Manchester Triage in Sweden - interrater reliability and accuracy.
AB  - INTRODUCTION: This study investigates the interrater reliability and the accuracy
      of Manchester Triage (MTS) at emergency departments in Western Sweden. METHODS: A
      group of 79 nurses from seven emergency departments assessed simulated patient
      cases and assigned triage categories using the same principles as in their daily
      work. K statistics, accuracy, over-triage and under-triage were then analyzed.
      The nurses performed 1027 triage assessments. RESULTS: The result showed an
      unweighted kappa value of 0.61, a linear weighted kappa value of 0.71, and a
      quadratic weighted kappa value of 0.81. The determined accuracy was 92% and 91%
      for the two most urgent categories, but significantly lower for the less urgent
      categories. CONCLUSIONS: Patients in need of urgent care were identified in more
      than nine out of 10 cases. The high level of over-triage and under-triage in the
      less urgent categories resulted in low agreement and accuracy. This may suggest
      that the resources of emergency departments can be overused for non-urgent
      patients.

PMID- 19577201
TI  - Nurse specialist treatment of eye emergencies: five year follow up study of
      quality and effectiveness.
AB  - The role of specialist nurses in triage, diagnosis and management of emergency
      eye conditions is well established, and encouraging reports of the safety and
      effectiveness of such services have been published. Specialist nurses in an
      emergency eye clinic in the UK seeing >7000 patients per year had been found at
      initial evaluation to treat 22% of the 1976 patients seen over a three month
      period without referring on to an ophthalmologist. A repeat of this evaluation
      five years later found this proportion had dropped to 17% (chi(2) = 16.7,
      p<0.01). In addition, the initial evaluation had found no incident of any patient
      having been treated and discharged by the specialist nurses returning to the
      department due to incorrect diagnosis or mismanagement. By contrast, from the
      sample 5 years later, 3 patients were identified who returned to the department
      due to possible misdiagnosis or sub-optimal management. We suggest that provision
      must be made for continuing professional development of nurses in this type of
      extended role, and the commitment to ongoing education should be backed up by a
      system of monitoring and critical incident reporting to facilitate skill
      maintenance and the life long learning process for specialist nurses.

PMID- 19577202
TI  - Emergency department management of penetrating eye injuries.
AB  - Penetrating injuries are rare but important for the patient both visually and
      socioeconomically. This guide intends to provide a structure for emergency
      department personnel to enable targeted history taking, effective examination,
      appropriate investigation and timely referral for those presenting with
      penetrating eye trauma.

PMID- 19577203
TI  - Rapid sequence induction anaesthesia: a guide for nurses in the emergency
      department.
AB  - Emergency rapid sequence induction (RSI) anaesthesia is the cornerstone of
      emergency airway management performed on patients in the emergency department
      (ED). The Royal College of Anaesthetists has stated that anaesthesia should not
      proceed without a skilled, dedicated assistant. It is essential that ED nurses
      are educated, skilled and competent to assist with RSI in the ED.

PMID- 19577204
TI  - Minor injury attendance times to the ED.
AB  - The Health Service Executive (HSE) highlights the need for effective patient
      throughput and management, whilst providing appropriate staffing and therapeutic
      interventions. It acknowledges that patient need is integral to the development
      of a nurse led service and advocates planning staffing levels to reflect arrival
      times of patients. An observational study of all patients who presented to the
      emergency department in July 2005 and February 2006 was undertaken (n=7768). The
      study identified 1577 patients suitable for treatment by the Advanced Nurse
      Practitioner (ANP) in these two months, which represents 20% of all patient
      attendances to the ED in this time period. A data collection tool was devised
      collectively by the ANPs to identify appropriate patients. The findings of the
      study revealed that 73% of patients suitable for the ANP service presented
      between the hours of 0800 and 2000, of which 54% attended between 0800 and 1600
      h. Sunday emerged as the busiest day in July 2005 whereas Monday was found to be
      the busiest day in February 2006. Friday was found to be consistently busy for
      both months.

PMID- 19577205
TI  - Splinting versus casting of "torus" fractures to the distal radius in the
      paediatric patient presenting at the emergency department (ED): a literature
      review.
AB  - AIM: To compare outcomes regarding splinting versus casting of paediatric torus
      fractures in the ED with the aim of establishing the preferred treatment.
      METHODS: Evidence was collated using electronic databases; Pubmed, Ovid, Medline
      and Cochrane library. Search terms included [torus fractures; buckle fractures;
      splinting distal radius fractures; paediatric wrist fractures; paediatric forearm
      fractures/injuries; cast versus splint]. Searches identified papers published
      between 1984 and June 2008. RESULTS: The review demonstrated that children with
      removable splints preferred them to casts, in terms of improved physical
      functioning and lower pain scores reported after initial injury than those with
      casts. Children demonstrated this by using their wrists in the first week after
      injury to shower and bathe more easily. The cast group reported unscheduled
      visits to ED due to problems with the cast, such as discomfort or re-application
      of the cast from getting it wet. Using a splint will have considerable economic
      implications, money was found to be saved in terms of time and resource
      management. Radiographs taken at 4 weeks in both the cast and splint group
      confirmed that all fractures healed without significant change in alignment,
      suggesting that neither clinical nor radiographic follow-up is necessary for
      injury. CONCLUSION: Torus splints in all the studies were consistently better
      than plaster immobilisation in terms of clinical outcome, patient preference and
      cost, with the exceptions of young children or children with special needs who
      can easily remove the device. Splinting torus fractures may reduce cost, time and
      resource management if used instead of casting in the ED.

PMID- 19577206
TI  - Severe toxic methemoglobinemia mimicking septic shock in an infant.

PMID- 19577208
TI  - Outcomes research in cardiovascular imaging: report of a workshop sponsored by
      the National Heart, Lung, and Blood Institute.
AB  - In July of 2008, the National Heart, Lung, and Blood Institute convened experts
      in noninvasive cardiovascular imaging, outcomes research, statistics, and
      clinical trials to develop recommendations for future randomized controlled
      trials of the use of imaging in: 1) screening the asymptomatic patient for
      coronary artery disease; 2) assessment of patients with stable angina; 3)
      identification of acute coronary syndromes in the emergency room; and 4)
      assessment of heart failure patients with chronic coronary artery disease with
      reduced left ventricular ejection fraction. This study highlights several
      possible trial designs for each clinical situation.

PMID- 19577209
TI  - International, multidisciplinary update of the 2006 Appropriateness Criteria for
      cardiac computed tomography.
AB  - BACKGROUND: A multi-society document outlining appropriateness criteria for
      cardiac CT (CCT) was published in 2006. Since then, CCT has experienced rapid
      growth in technologic advances and clinical use. We sought to reassess opinion
      about the appropriate use of CCT among an international group of experts in the
      field. METHODS: Seventy-two international experts in the field of CCT
      independently rated all 39 indications listed in the original 2006
      appropriateness statement. Indications were classified as either "appropriate,"
      "uncertain," or "inappropriate" based on an assessment of the clinical balance
      between risk and benefit to the patient in daily practice. Median rater scores
      were considered to represent current opinion for each indication and were
      compared with the original value in the 2006 document. RESULTS: Survey
      respondents averaged 5.8+/-4.1 years of CCT experience, with a median total of
      1200 contrast-enhanced CCT examinations performed and interpreted. Cardiologists
      (40; 55.6%) and radiologists (32; 44.4%) were included. Five of 12 previously
      "uncertain" indications shifted to "appropriate," resulting in a total of 18
      "appropriate" of 39 possible indications. Conversely, all previously
      "appropriate" indications remained so. Among the 14 previously "inappropriate"
      indications, 10 shifted to "uncertain," none to "appropriate." Overall, 26 of 39
      indications showed increased appropriateness scores (range of shift, 1-4 points;
      median value, 1; interquartile range, 0-2). No significant differences were
      observed between US and non-US expert respondents or between cardiology and
      radiology respondents in the overall appropriateness category ratings.
      CONCLUSIONS: When compared with the 2006 Appropriateness Criteria, opinion
      regarding clinical use of CCT has experienced a significant shift toward
      appropriateness across most indications, similarly judged among international
      cardiology and radiology experts in the field.

PMID- 19577210
TI  - Role of opinion in appropriate use criteria.

PMID- 19577211
TI  - Feasibility of dual-source cardiac CT angiography with high-pitch scan protocols.
AB  - BACKGROUND: Cardiac CT angiography (CCTA) has become a frequently used diagnostic
      tool in clinical practice, but concern remains about the radiation exposure.
      Because of the second x-ray acquisition system, dual-source CT systems might
      allow for high-pitch CT data acquisition and thus for examination of the whole
      heart during a single heart beat, with the potential for radiation dose
      reduction. OBJECTIVE: We assessed the feasibility of a high-pitch scan mode with
      a dual-source CT system. METHODS: High-pitch modes were used in patients
      undergoing CCTA with a dual-source CT system. Diagnostic image quality for
      cardiac structures and coronary arteries was assessed. Radiation dose was
      estimated from the scanner-generated dose-length product (DLP). RESULTS: CCTA was
      performed in 14 patients during a single heart beat applying a pitch value of
      3.4. Mean heart rate during examination was 56.4+/-8.1 beats/min. Diagnostic
      image quality for the assessment of larger cardiac structures was obtained in all
      patients, whereas diagnostic image quality could be achieved in 82% of all
      coronary segments. With a mean DLP of 145+/-47 mGy x cm, the resulting estimated
      radiation dose was 2.0+/-0.7 mSv. CONCLUSIONS: This proof-of-concept study shows
      the ability of dual-source CT scanners to scan the whole heart during one single
      heart beat at low radiation dose.

PMID- 19577212
TI  - High-pitch prospectively electrocardiogram-triggered helical data acquisition: a
      new tool for the cardiac CT toolbox?

PMID- 19577213
TI  - High-definition multidetector computed tomography for evaluation of coronary
      artery stents: comparison to standard-definition 64-detector row computed
      tomography.
AB  - BACKGROUND: The assessment of coronary stents with present-generation 64-detector
      row computed tomography scanners that use filtered backprojection and operating
      at standard definition of 0.5-0.75 mm (standard definition, SDCT) is limited by
      imaging artifacts and noise. OBJECTIVES: We evaluated the performance of a novel,
      high-definition 64-slice CT scanner (HDCT), with improved spatial resolution
      (0.23 mm) and applied statistical iterative reconstruction (ASIR) for evaluation
      of coronary artery stents. METHODS: HDCT and SDCT stent imaging was performed
      with the use of an ex vivo phantom. HDCT was compared with SDCT with both smooth
      and sharp kernels for stent intraluminal diameter, intraluminal area, and image
      noise. Intrastent visualization was assessed with an ASIR algorithm on HDCT
      scans, compared with the filtered backprojection algorithms by SDCT. RESULTS: Six
      coronary stents (2.5, 2.5, 2.75, 3.0, 3.5, 4.0mm) were analyzed by 2 independent
      readers. Interobserver correlation was high for both HDCT and SDCT. HDCT yielded
      substantially larger luminal area visualization compared with SDCT, both for
      smooth (29.4+/-14.5 versus 20.1+/-13.0; P<0.001) and sharp (32.0+/-15.2 versus
      25.5+/-12.0; P<0.001) kernels. Stent diameter was higher with HDCT compared with
      SDCT, for both smooth (1.54+/-0.59 versus1.00+/-0.50; P<0.0001) and detailed
      (1.47+/-0.65 versus 1.08+/-0.54; P<0.0001) kernels. With detailed kernels, HDCT
      scans that used algorithms showed a trend toward decreased image noise compared
      with SDCT-filtered backprojection algorithms. CONCLUSIONS: On the basis of this
      ex vivo study, HDCT provides superior detection of intrastent luminal area and
      diameter visualization, compared with SDCT. ASIR image reconstruction techniques
      for HDCT scans enhance the in-stent assessment while decreasing image noise.

PMID- 19577214
TI  - True high-definition in cardiac imaging will require 4 dimensions of technologic
      innovation.

PMID- 19577215
TI  - First experience with 320-row multidetector CT coronary angiography scanning with
      prospective electrocardiogram gating to reduce radiation dose.
AB  - BACKGROUND: The 320-row multidetector CT (MDCT) provides the capability for
      prospective electrocardiogram-gated cardiac CT angiography. OBJECTIVE: We
      assessed the effective radiation doses of MDCT with a 320-row detector volume
      scanner. METHODS: Two hundred patients underwent clinically directed cardiac
      scanning (100 kVp, n=9 or 120 kVp, n=191; range, 300-580 mA). Effective radiation
      dose (in mSv) was estimated from extended dose-length product. For heart rates
      (HRs) <65 beats/min, exposure phase was 65% up to the end of R wave of the
      cardiac cycle, using a one-heart beat acquisition and half-scan reconstruction.
      HRs from 66 to 79 beats/min and > or =80 beats/min were scanned with either 2- or
      3-heart beat acquisitions, respectively. Patients with arrhythmias were not
      excluded. RESULTS: The mean effective dose was 5.7+/-1.7 mSv (range, 1.6-11.1
      mSv) for 151 patients (75%) scanned with a one-heart beat acquisition.
      Qualitative image quality was assessed to be in good to excellent range, and
      mottle image quality was in low-to-medium mottle range. For patients scanned with
      2- or 3-heart beat acquisition, radiation dose was higher with mean exposures of
      13.0+/-3.3 mSv and 19.5+/-5.3 mSv, respectively. CONCLUSIONS: Low effective
      radiation dose with acceptable image quality on 320-row MDCT can be achieved with
      one-heart beat scan acquisition when HR is <65 beats/min. Further reduction in
      dose can likely also be achieved by modification of the prospective-gated imaging
      parameters.

PMID- 19577216
TI  - Reducing radiation dose in CT angiography with wide-detector and single-heart
      beat acquisition.

PMID- 19577218
TI  - Multislice coronary computed tomographic angiography in emergency department
      presentations of unsuspected acute myocardial infarction.
AB  - BACKGROUND: Coronary computed tomographic angiography (CCTA) is not indicated in
      the setting of acute myocardial infarction in the emergency department (ED).
      Nonetheless, acute coronary syndromes may have atypical presentations, and CCTA
      may be inadvertently performed in this setting. OBJECTIVES: This study was
      designed to determine the frequency and characteristics of CCTA imaging of
      unsuspected acute myocardial infarction in the ED. METHODS: All CCTAs performed
      in the ED at Lenox Hill Hospital were reviewed for clinical indications and
      subsequent course; patients with documented acute myocardial infarction were
      identified. RESULTS: Of the 500 CCTAs performed on ED patients in the Lenox Hill
      laboratory, 5 patients (1%) were imaged during the initial phase of an
      unsuspected acute myocardial infarction; in all cases the CCTAs were key to the
      diagnosis. The imaging characteristics were (1) total or subtotal occlusion and
      (2) transmural hypodensity in the infarct area. CONCLUSION: Although acute
      myocardial infarction on CCTA in ED patients is an infrequent event, proper and
      prompt recognition is critical for appropriate patient care, particularly as
      applications to the ED increase.

PMID- 19577219
TI  - Extensive recurrent cardiac lipoma.
AB  - A 56-year-old woman with a history of surgical removal of a invasive myocardial
      lipoma presented with progressive dyspnea. Transthoracic echocardiogram showed
      severe mitral and tricuspid regurgitation and severely impaired biventricular
      systolic function. Cardiac computed tomography was performed, showing extensive
      biventricular basal and mid-myocardial replacement by an infiltrating tumor that
      had the density of fat resulting in large aneurysms of the basal segments of both
      the ventricles. The patient is currently awaiting orthotopic heart
      transplantation.

PMID- 19577217
TI  - Rationale and design of a randomized controlled trial comparing stress myocardial
      perfusion imaging with coronary CT angiography as the initial imaging study for
      intermediate-risk patients admitted with chest pain.
AB  - BACKGROUND: Noninvasive cardiac imaging plays an important role in the diagnosis
      and management of coronary artery disease (CAD). Prior studies have focused on
      the diagnostic performance of noninvasive modalities using angiographically
      significant stenoses as the reference standard. Recent trends in evidence-based
      medicine and increasing imaging utilization call for validation of diagnostic
      algorithms with well-designed, controlled trials with clinical outcome endpoints.
      OBJECTIVE: To compare the performance of stress radionuclide myocardial perfusion
      imaging (MPI) and coronary computed tomography angiography (CTA) in terms of
      outcomes. METHODS: We designed a single-center, randomized controlled trial that
      compares MPI and CTA as the initial modality for the evaluation of patients
      hospitalized for chest pain without known CAD or acute myocardial infarction.
      Patients with intermediate-risk characteristics and a clinical need for
      noninvasive imaging are included. The primary outcome measured is the incidence
      of conventional angiography not leading to subsequent coronary revascularization
      within 1 year. The study is powered to detect a reduction from 11% to 3% in
      catheterization not leading to an intervention with a sample size of 400.
      Secondary outcomes include procedural complications and posttest renal
      dysfunction (safety outcomes), major adverse cardiovascular events, length of
      hospital stay, subsequent hospitalizations and imaging, changes in medical
      management, and tolerability of the noninvasive test. CONCLUSIONS: The results of
      this trial will further our understanding of the relative appropriateness of CTA
      and MPI in evaluating intermediate-risk patients hospitalized with chest pain. It
      will also have implications for the design and probability of success of
      multicentered trials that are currently being planned.

PMID- 19577221
TI  - President's page.

PMID- 19577222
TI  - Using feature preview to investigate the roles of top-down and bottom-up
      processing in conjunction search.
AB  - The venerable conjunction search paradigm is a widely used tool to investigate
      how we search for items of interest from among visually complex surroundings.
      Models of visual search have long predicted that standard conjunction search is
      guided primarily by top-down processing. Prior attempts to test this claim
      experimentally have done so by altering some aspect of the standard conjunction
      search, whether by manipulating the distractor ratio or by including a feature
      singleton. Although suggestive, these manipulations result in a task that differs
      slightly from standard conjunction search. To leave the standard conjunction
      search paradigm intact, we used the feature preview task developed by Olds and
      Fockler [Olds, E. S., & Fockler, K. A. (2004). Does previewing one stimulus
      feature help conjunction search? Perception, 33, 195-216]. Our results show that
      in standard conjunction search the effect of bottom-up activation is not
      necessarily detrimental to search performance as previously suggested by
      computational models of visual search. Instead, bottom-up activation limits the
      scope of search, thereby boosting the efficiency of standard conjunction
      searches. Subjects also showed a bias to group items by color rather than
      orientation even when color differences were reduced nearly to threshold,
      indicating that the salience advantage of color is complemented by a general
      bottom-up preference for color.

PMID- 19577223
TI  - Implicit and explicit attitude dissociation in spontaneous deceptive behavior.
AB  - Society considers deception to be an improper act but at the same time, people
      deceive each other surprisingly often during interpersonal interactions. In our
      study, this hypocrisy was assumed to be derived from ambivalent attitudes
      stemming from different sources, which we divided into implicit and explicit.
      Using a simulated racing task in a virtual environment, we identified
      participants who chose to be deceptive. Twenty two of the 60 subjects
      spontaneously decided to cheat in order to gain monetary compensation, while the
      other 38 subjects chose to be honest. We compared these two groups' implicit
      beliefs about deception using the Implicit Association Test (Deception-IAT), as
      well as their explicit attitudes about deception and their personalities using
      self-report questionnaires. There was no difference between the two groups in
      explicit attitude or personality; however, the group who cheated on the racing
      task showed their implicit preference for deception more than that of the group
      who acted honestly as measured by the Deception-IAT.

PMID- 19577224
TI  - What you believe is what you want: modeling PTSD-related treatment preferences
      for sertraline or prolonged exposure.
AB  - Despite the known efficacy of various psychotherapies and pharmacotherapies for
      posttraumatic stress disorder (PTSD), we know little about what factors predict
      treatment preference. In the present study, we first developed exploratory path
      models of treatment preference for a psychotherapy or pharmacotherapy (n=273) and
      then conducted confirmatory analyses of these models in a second sample (n=324)
      and in a third generalization sample of trauma-exposed women (n=105). We examined
      demographic and psychopathology factors and treatment-related beliefs (i.e.,
      credibility and personal reactions). Across all samples, treatment-related
      beliefs were the strongest predictors of treatment preference. Further, severity
      of depression directly reduced the likelihood of choosing psychotherapy, and
      severity of PTSD directly increased the likelihood of choosing pharmacotherapy.
      These results underscore the importance of better understanding individual's
      beliefs regarding treatments. With a clearer understanding of these factors, we
      may be able to reduce barriers to treatment and increase access to effective
      treatments for those with trauma-related symptoms.

PMID- 19577225
TI  - Brooding and reflective rumination among suicide attempters: cognitive
      vulnerability to suicidal ideation.
AB  - Previous research suggests that the brooding subtype of rumination is associated
      with increased suicidal ideation, but findings are inconsistent with respect to
      reflection, considered to be the more adaptive form of rumination. This study
      investigated the circumstances under which reflective rumination might be
      associated with increased suicidal ideation by examining whether a suicide
      attempt history moderated the relationship between the ruminative subtypes and
      current suicidal ideation. Thirty-seven young adults who reported a past suicide
      attempt and fifty-nine young adults without a suicide attempt history completed
      measures of rumination and depression symptoms in an initial study session. They
      then completed a measure of suicidal ideation and hopelessness during a second
      study session. Overall, brooding was associated with higher self-reported
      suicidal ideation, whereas reflection was not significantly associated with
      ideation. However, reflection - but not brooding - interacted with suicide
      attempt history to statistically predict suicidal ideation, even after adjusting
      for symptoms of depression and hopelessness, whereas brooding no longer predicted
      ideation after adjusting for these symptoms. These findings qualify earlier
      suggestions that reflection is a more adaptive form of rumination by indicating
      that among vulnerable individuals - in particular those with a history of a
      suicide attempt - a higher degree of reflective rumination is associated with
      increased suicidal ideation.

PMID- 19577228
TI  - Effects of macrophage colony-stimulating factor on microglial responses to
      lipopolysaccharide and beta amyloid.
AB  - A challenge for studies involving microglia cultures is obtaining sufficient
      cells for downstream experiments. Macrophage colony-stimulating factor (M-CSF)
      has been used to improve yield of microglia in culture. However, the effects of M
      CSF on activation profiles of microglia cultures are still unclear. Microglia
      activation is characterised by upregulation of co-stimulatory molecules and an
      inflammatory phenotype. The aim of this study is to demonstrate whether M-CSF
      supplementation alters microglial responses in resting and activated conditions.
      Microglia derived from mixed glia cultures and the BV-2 microglia cell line were
      cultivated with/without M-CSF and activated with lipopolysaccharide (LPS) and
      beta amyloid (Abeta). We show M-CSF expands primary microglia without affecting
      microglial responses to LPS and Abeta, as shown by the comparable expression of
      MHC class II and CD40 to microglia grown without this growth factor. M-CSF
      supplementation in BV-2 cells had no effect on nitric oxide (NO) production.
      Therefore, M-CSF can be considered for improving microglia yield in culture
      without introducing activation artefacts.

PMID- 19577227
TI  - Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced
      neurodegeneration.
AB  - BACKGROUND: Alcoholism may result in severe neurological deficits and cognitive
      impairments. Many of the central effects of ethanol (EtOH) can be explained by
      upregulation of N-methyl-D-aspartate (NMDA) and downregulation of gamma
      aminobutyric acid (GABA) A receptors (GABAA) in response to long-term EtOH
      consumption. Abrupt ethanol withdrawal (EW) may result in neuronal
      hyperexcitability leading to hallucinations, seizures, neurodegeneration, and
      sometimes death. METHODS: Using a multidisciplinary approach in wild-type and
      genetically modified mice, we examined the contribution of the tissue plasminogen
      activator (tPA), plasminogen, and laminin to EW-induced cell death. RESULTS: Here
      we show that EW-induced neurodegeneration is mediated by the tPA/plasmin system.
      During EW, tPA is upregulated in the hippocampus and converts plasminogen to
      plasmin, which in turn degrades an extracellular matrix component laminin,
      leading to caspase-3-dependent cell death. Consequently, mice in which the tPA or
      plasminogen genes have been deleted do not show EW-induced laminin degradation,
      mitochondrial dysfunction, and neurodegeneration. Finally, we demonstrated that
      disruption of the hippocampal laminin gamma-1 renders the mice resistant to
      neurotoxic effects of EW. CONCLUSIONS: Our data identify laminin gamma-1 as a
      novel target to combat neurodegeneration.

PMID- 19577226
TI  - Paternal transmission of complex phenotypes in inbred mice.
AB  - BACKGROUND: Inbred mice are genetically identical but nonetheless demonstrate
      substantial variability in complex behaviors such as activity levels in a novel
      environment. This variability has been associated with levels of parental care
      experienced early in development. Although maternal effects have been reported in
      biparental and uniparental strains, there have been no investigations of paternal
      effects in non-biparental strains in which offspring are reared exclusively by
      mothers. METHODS: In the uniparental inbred Balb/cJ mouse strain, we examined the
      relationship of paternal open-field activity to the activity of both male and
      female offspring in the open-field. Potential mediators of paternal transmission
      of behavior were examined, including maternal care, growth parameters, litter
      characteristics, and time the father was present with the pregnant mother
      prenatally. RESULTS: An association of paternal open-field activity with the open
      field activity of female but not male offspring was found. Variation in maternal
      postnatal care was associated with female but not male offspring activity in the
      open-field but did not mediate paternal effects on offspring behavior. Paternal
      effects on offspring growth parameters were present, but these effects also did
      not mediate paternal effects on behavior. CONCLUSIONS: Paternal transmission of
      complex traits in genetically identical mice reared only by mothers suggests a
      nongenetic mechanism of inheritance potentially mediated by epigenetic factors.
      The exclusion of multiple mediators of paternal effects on offspring suggests the
      possibility of germline paternal inheritance via sperm of complex phenotypes in
      inbred mice. Future studies are required to examine these interesting
      possibilities.

PMID- 19577229
TI  - Histocompatibility testing of cultivated human bone marrow stromal cells - a
      promising step towards pre-clinical screening for allogeneic stem cell therapy.
AB  - Mesenchymal stem cells (MSCs) lack major histocompatibility complex (MHC)-II and
      only show minimal MHC-I expression. Despite MSCs demonstrating T-cell anergy,
      there are no established methods to evaluate their suitability. It is crucial to
      evaluate the complete mismatch of MHC compatibility in view of the hypo
      immunogenic nature and immunomodulatory properties of MSCs with respect to their
      proliferation potential (PP) and utility in terms of passage number. With bone
      marrow (BM) being the major source of MSCs, the use of these cells becomes even
      more complicated, due to many other receptors coming to fore and triggering
      alternative pathways. This prospective study included five BM aspirates for MSC
      cultures and five allogeneic peripheral blood mono nuclear cells (PBMNCs) from
      healthy volunteers. MHC compatibility was assessed by polymerase chain reaction
      sequence specific primer (PCR-SSP). The PP and a T-cell response to MSCs was
      addressed in mixed cultures and evaluated on the basis of their stimulation index
      (SI). Allogeneic circulatory antibodies against the donor MSCs was performed by
      cytotoxicity assay. The PP of MSCs during interactions with PBMNCs (T-cells)
      demonstrated T-cell anergy and the response to circulatory antibodies was
      minimal, in consonance with other published reports. Although, the results are
      encouraging for potential clinical application of MSC transplantation, autologous
      is always preferable to allogeneic, at least until the long-term safety of these
      cells is established in clinical trials.

PMID- 19577231
TI  - [Hepatic pleomorphic sarcoma over a non-parasitic hepatic cyst].

PMID- 19577232
TI  - Proposed guidelines for increasing the reliability and validity of Letournel
      classification system.
AB  - The aim of this study was to improve the reliability of Letournel classification
      system using a guideline algorithm protocol. The study was conducted upon two
      groups of orthopaedic surgeons with different experience and was consisted of two
      observation sessions (A and B). In session A, every observer studied, with no
      instructions or guidelines, a particular set of acetabular fractures on AP and
      Judet oblique views. In session B the observers had to examine the same set of
      radiographs by taking into account a guideline algorithm protocol. The unweighted
      kappa coefficient was utilised to estimate the observers' agreement arising from
      the examination of the given X-rays. Finally, the agreement of the observers,
      related to the intraoperative diagnosis was estimated. The main finding of the
      herein study lies on the improvement of the agreement rate experienced within
      both groups, in session B over session A. It is reasonable to assume that the
      main reason behind this result is the provision of the guideline algorithm
      protocol in the second session. The total agreement rate was increased from 59.9%
      in session A to 72.1% in session B, (p value=0.0267). Our findings confirm the
      reliability of Letournel classification system and the proposed guideline
      algorithm protocol further improve the ability to classify the most complex
      acetabular fractures types.

PMID- 19577230
TI  - Age-related changes in lck-Vav signaling pathways in mouse CD4 T cells.
AB  - Activation of lck-fyn kinases during T cell receptor signaling leads to Vav
      phosphorylation, activation of downstream targets including Rac1, and a transient
      decline in ezrin and moesin phosphorylation. We have shown that age increases
      Rac1 activity and lowers ezrin and moesin phosphorylation in resting mouse CD4
      cells, changes that could be the results of alterations in lck-Vav signaling.
      Analysis of Vav in CD4 cells from old mice shows increases in the phosphorylation
      of two key regulatory residues, Tyr160 and Tyr174, suggesting enhancement of Vav
      GTPase activity. In addition, analysis of lck status also shows age-related
      increases in phosphorylation of two key residues, Tyr394 and Tyr505, which have
      opposite effects on lck function. These changes in lck-Vav signals in resting CD4
      cells may contribute in turn to age-related increases in Rac1 activity and
      declines in phosphorylation of cytoskeletal proteins including Ezrin and Moesin.

PMID- 19577233
TI  - Age at menopause in rural El Salvador.

PMID- 19577234
TI  - Sex trafficking, violence victimization, and condom use among prostituted women
      in Nicaragua.

PMID- 19577235
TI  - Intrapartum translabial ultrasound demonstrating brow presentation during the
      second stage of labor.

PMID- 19577236
TI  - Effect of body mass index on clinical manifestations in patients with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To determine whether there is a correlation between body mass index
      (BMI) and blood pressure or clinical features such as hirsutism in women with
      polycystic ovary syndrome (PCOS). METHOD: In this cross-sectional study, 62 women
      with PCOS were allocated to one of 3 groups according to a BMI range defining
      normal weight, overweight, or obesity. Blood pressure, waist-to-hip ratio,
      Ferriman and Gallwey hirsutism score, and presence of acne were recorded for each
      participant and the means were compared among groups. RESULTS: The overall mean
      age was 35.85+/-5.03 years; BMI, 31.91+/-6.40; systolic and diastolic blood
      pressure, 113.02+/-16.10 mm Hg and 71.79+/-10.04 mm Hg; waist-to-hip ratio,
      0.82+/-0.07; and hirsutism score, 3.63+/-4.35. Acne was present in 24
      participants. Of these, 8 (33.3%) were overweight and 13 (54.2%) obese. When
      groups were compared, a progressive and significant increase in systolic and
      diastolic blood pressure was observed from the normal weight to the obese group.
      CONCLUSION: We observed a significant and progressive correlation between BMI and
      both blood pressure and clinical features in women with PCOS.

PMID- 19577237
TI  - Inner strength--a theoretical analysis of salutogenic concepts.
AB  - BACKGROUND: Theoretical and empirical overlaps between the concepts of
      resilience, sense of coherence, hardiness, purpose in life, and self
      transcendence have earlier been described as some kind of inner strength, but no
      studies have been found that focus on what attributes these concepts have in
      common. OBJECTIVES: The objective of this study was to perform a theoretical
      analysis of the concepts of resilience, sense of coherence, hardiness, purpose in
      life, and self-transcendence, in order to identify their core dimensions in an
      attempt to get an overarching understanding of inner strength. PRINT METHOD: An
      analysis inspired by the procedure of meta-theory construction was performed. The
      main questions underlying the development of the concepts, the major paradigms
      and the most prominent assumptions, the critical attributes and the
      characteristics of the various concepts were identified. RESULTS: The analysis
      resulted in the identification of four core dimensions of inner strength and the
      understanding that inner strength relies on the interaction of these dimensions:
      connectedness, firmness, flexibility, and creativity. These dimensions were
      validated through comparison with the original descriptions of the concepts.
      CONCLUSION: An overarching understanding of inner strength is that it means both
      to stand steady, to be firm, with both feet on the ground and to be connected to;
      family, friends, society, nature and spiritual dimensions and to be able to
      transcend. Having inner strength is to be creative and stretchable, which is to
      believe in own possibilities to act and to make choices and influence life's
      trajectory in a perceived meaningful direction. Inner strength is to shoulder
      responsibility for oneself and others, to endure and deal with difficulties and
      adversities. This knowledge about inner strength will raise the awareness of the
      concept and, in turn, hopefully increase our potential to support people's inner
      strength.

PMID- 19577238
TI  - Gas chromatographic-mass spectrometric fragmentation study of phytoestrogens as
      their trimethylsilyl derivatives: identification in soy milk and wastewater
      samples.
AB  - An analytical method for the identification of eight plant phytoestrogens
      (biochanin A, coumestrol, daidzein, equol, formononetin, glycitein, genistein and
      prunetin) in soy products and wastewater samples was developed using gas
      chromatography coupled with ion trap mass spectrometry (GC/MS-MS). The
      phytoestrogens were derivatized as their trimethylsilyl ethers with
      trimethylchlorosilane (TMCS) and N,O-bis(trimethylsilyl)trifluoroacetamide
      (BSTFA). The phytoestrogens were isolated from all samples with liquid-liquid
      extraction using ethyl acetate. Daidzein-d(4) and genistein-d(4) labeled
      standards were used as internal standards before extraction and derivatization.
      The fragmentation patterns of the phytoestrogens were investigated by isolating
      and fragmenting the precursor ions in the ion-trap and a typical fragmentation
      involved the loss of a methyl and a carbonyl group. Two characteristic fragment
      ions for each analyte were chosen for identification and confirmation. The
      developed methodology was applied to the identification and confirmation of
      phytoestrogens in soy milk, in wastewater effluent from a soy-milk processing
      plant, and in wastewater (influent and effluent) from a treatment plant. Detected
      concentrations of genistein ranged from 50,000 microg/L and 2000 microg/L in soy
      milk and in wastewater from a soy-plant, respectively, to 20 microg/L and <1
      microg/L for influent and effluent from a wastewater treatment plant,
      respectively.

PMID- 19577239
TI  - Temporal variability of colloidal material in agricultural storm runoff from
      managed grassland using flow field-flow fractionation.
AB  - This paper reports the use of flow field-flow fractionation (FlFFF) to determine
      the temporal variability of colloidal (<1mum) particle size distributions in
      agricultural runoff waters in a small managed catchment in SW England during
      storm events. Three storm events of varying intensity were captured and the
      colloidal material in the runoff analysed by FlFFF. The technique had sufficient
      sensitivity to determine directly the changing colloidal profile over the 0.08
      1.0mum size range in the runoff waters during these storm events. Rainfall, total
      phosphorus and suspended solids in the bulk runoff samples were also determined
      throughout one storm and showed significant correlation (P<0.01) with the amount
      of colloidal material. Whilst there are some uncertainties in the resolution and
      absolute calibration of the FlFFF profiles, the technique has considerable
      potential for the quantification of colloidal material in storm runoff waters.

PMID- 19577240
TI  - Analysis of trace levels of domoic acid in seawater and plankton by liquid
      chromatography without derivatization, using UV or mass spectrometry detection.
AB  - Quantitation of trace levels of domoic acid (DA) in seawater samples usually
      requires labour-intensive protocols involving chemical derivatization with 9
      fluorenylmethylchloroformate and liquid chromatography with fluorescence
      detection (FMOC-LC-FLD). Procedures based on LC-MS have been published, but time
      consuming and costly solid-phase extraction pre-concentration steps are required
      to achieve suitable detection limits. This paper describes an alternative, simple
      and inexpensive LC method with ultraviolet detection (LC-UVD) for the routine
      analysis of trace levels of DA in seawater without the use of sample pre
      concentration or derivatization steps. Qualitative confirmation of DA identity in
      dubious samples can be achieved by mass spectrometry (LC-MS) using the same
      chromatographic conditions. Addition of an ion-pairing/acidifying agent (0.15%
      trifluoroacetic acid) to sample extracts and the use of a gradient elution
      permitted the direct analysis of large sample volumes (100 microl), resulting in
      both high selectivity and sensitivity (limit of detection=42 pg ml(-1) by LC-UVD
      and 15 pg ml(-1) by LC-MS). Same-day precision varied between 0.4 and 5%,
      depending on the detection method and DA concentration. Mean recoveries of spiked
      DA in seawater by LC-UVD were 98.8% at 0.1-10 ng ml(-1) and 99.8% at 50-1000 ng
      ml(-1). LC-UVD exhibited strong correlation with FMOC-LC-FLD during inter
      laboratory analysis of Pseudo-nitzschia multiseries cultures containing 60-2000
      ng DA ml(-1) (r(2)>0.99), but more variable results were obtained by LC-MS
      (r(2)=0.85). This new technique was used to confirm the presence of trace DA
      levels in low-toxicity Pseudo-nitzschia spp. isolates (0.2-1.6 ng ml(-1)) and in
      whole-water field samples (0.3-5.8 ng ml(-1)), even in the absence of detectable
      Pseudo-nitzschia spp. cells in the water column.

PMID- 19577241
TI  - Analysis of chlorophenols, bisphenol-A, 4-tert-octylphenol and 4-nonylphenols in
      soil by means of ultrasonic solvent extraction and stir bar sorptive extraction
      with in situ derivatisation.
AB  - A novel method based on ultrasonic solvent extraction and stir bar sorptive
      extraction for the analysis of phenolic organic pollutants including
      chlorophenols, bisphenol-A, 4-tert-octylphenol and 4-nonylphenol in soil samples
      was developed. The different parameters that affect both the extraction of
      analytes from the soil samples, such as solvent selection, extraction time, and
      the partitioning from the solvent/water mix to poly(dimethylsiloxane) (PDMS) were
      studied. The final selected conditions consisted of the extraction of 1g 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 stir bar sorptive extraction
      with in situ derivatisation. The stir bars were analyzed by thermal desorption
      gas chromatography-mass spectrometry (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 and by comparing the analysis of real samples with the
      proposed method and a classical method using pressurized solvent extraction (PSE)
      GC-MS. The main advantage of this method is a substantial solvent reduction. For
      the extraction of only 1g of solid sample allowing limits of detection ranging
      from 0.2 to 1.7 microg kg(-1) dw. Repeatability and reproducibility variation
      were lower than 20% for all investigated compounds. Results of the certified
      reference materials and the real samples verify the high accuracy of this method.

PMID- 19577242
TI  - Determination of hydroxylated metabolites of polycyclic aromatic hydrocarbons in
      human hair by gas chromatography-negative chemical ionization mass spectrometry.
AB  - The study describes the determination of mono-hydroxylated polycyclic aromatic
      hydrocarbons (OH-PAHs), metabolites of PAHs, in human hair. Twelve selected OH
      PAHs from two to four rings, generally determined in urine analysis, were
      investigated as markers of human exposure to PAHs. Following hydrolysis of hair
      specimens of 50-300 mg with 1M NaOH, OH-PAHs were extracted using dichloromethane
      and submitted to an optimized derivatization with (2S,4R)-N-heptafluorobutyryl-4
      heptafluorobutoyloxy-prolyl chloride. Compounds were then analyzed using gas
      chromatography-negative chemical ionization mass spectrometry (GC-NCIMS). The
      average inter-day and intra-day variability was 12% and 17%, respectively. The
      average recovery was 52% and the limits of detection and quantification ranged
      from 20 and 66 pmol/g for 1-OH-phenanthrene (i.e., 3.9 and 12.8 pg/mg) to 311 and
      1030 pmol/g for 2-OH-benzo(c)phenanthrene (i.e., 75.9 and 251 pg/mg). The
      influence of hair washing with water as decontamination step, and enzymatic
      treatment (beta-glucuronidase) to hydrolyze conjugated derivatives were also
      tested. The application of the developed method to the analysis of 30 hair
      specimens (17 from non-smoker and 13 from smoker volunteers) demonstrated inter
      individual qualitative and quantitative variations. According to the easiness of
      hair sampling and based on the extended detection windows provided by hair
      analysis, this method is proposed as a new promising tool for the assessment of
      human chronic exposure to PAHs.

PMID- 19577243
TI  - Calorimetric measurements of proton adsorption onto Pseudomonas putida.
AB  - Having an understanding of the reactive nature of the bacterial surface is
      enhanced when its reactivity is considered in a thermodynamic framework. Towards
      this end, isothermal titration calorimetry was used to measure heats of proton
      adsorption onto Pseudomonas putida, a common gram negative soil bacterium. Proton
      adsorption generated large exothermic heats and proton uptake continued down to
      pH 2.5. Applying a surface complexation model to the calorimetric data allowed
      for the derivation of site-specific enthalpies and entropies of proton
      adsorption. The 4-site non-electrostatic model of Borrok et al. [D.M. Borrok,
      J.B. Fein, J. Colloid Interface Sci. 286 (2005) 110] was chosen to describe
      proton adsorption and enabled derivation of site-specific enthalpies of -2.4+/
      0.3, -3.7+/-0.2, -9.0+/-0.6, and -36.0+/-1.2 kJ/mol for Sites 1-4, respectively.
      Entropies of proton adsorption were calculated to be 51+/-3, 75+/-1, 91+/-2, and
      55+/-4 J/mol K, for Sites 1-4, respectively. Enthalpies and entropies of Sites 1
      and 3 are consistent with that of multifunctional organophosphonic acids, Site 2
      is consistent with multifunctional carboxylic acids, and Site 4 is consistent
      with an amine. Temperature dependence of the acidity constants for Sites 1-3 is
      predicted to be minimal; however, Site 4 is predicted to more substantially
      affected by temperature.

PMID- 19577244
TI  - An unusual case of left anterior descending coronary artery occlusion--anterior
      ST depression and inferior ST elevation.

PMID- 19577245
TI  - Diagnostic accuracy of extended-length electrocardiogram in differentiating
      between athlete's heart and hypertrophic cardiomyopathy.
AB  - BACKGROUND: Standard 12-lead electrocardiogram (ECG) has several limitations in
      solving the differential diagnosis between physiologic left ventricular
      hypertrophy (PLVH) and hypertrophic cardiomyopathy (HCM), given the high rate of
      false-positive results in athletes. The aim of this study was to assess the
      usefulness of several arrhythmic risk indexes in differentiating PLVH from HCM.
      METHODS: A multiparametric ECG analysis (extended-length ECG) was performed on 30
      male athletes with PLVH and 30 male patients with HCM, with homogeneous age
      distribution. RESULTS: The combination of 4 extended-length ECG variables,
      namely, corrected QT interval (Bazett), QT dispersion, mean resting heart rate,
      and low-amplitude signal duration at 25 Hz (low-amplitude signal duration at the
      end of filtered QRS) displayed remarkable diagnostic accuracy (area under
      receiver operating characteristic curve, 94%). The same accuracy was obtained
      replacing QT dispersion with T-wave complexity index. CONCLUSIONS: Extended
      length ECG can be considered an effective, low-cost, and low time-consuming
      clinical tool for distinguishing between PLVH and HCM.

PMID- 19577246
TI  - Noncitrated whole blood is optimal for evaluation of postinjury coagulopathy with
      point-of-care rapid thrombelastography.
AB  - INTRODUCTION: Progressive postinjury coagulopathy has become the fundamental
      rationale for damage control surgery, and the decision to abort operative
      intervention must occur prior to overt laboratory confirmation of coagulopathy.
      Current coagulation testing is most commonly performed for monitoring
      anticoagulation therapy, the results are delayed, and the applicability of these
      tests in the trauma setting is questionable. Point-of-care (POC) rapid
      thrombelastography (r-TEG) provides real time analysis of thrombostatic function,
      which may allow for accurate, goal directed therapy. The test differs from
      standard thrombelastography (TEG) because the clotting process and subsequent
      analysis is accelerated by the addition of tissue factor to the whole blood
      sample, but is limited by the requirement that the analysis be performed within 4
      min of blood draw to prevent clot formation. Consequently, citrated specimens
      have been proposed to obviate this time limitation. We hypothesized that the
      speed of r-TEG analysis following tissue factor addition to citrated blood might
      compromise accurate determinations compared with noncitrated whole blood.
      Additionally, we sought to compare the use of r-TEG with conventional coagulation
      tests in analysis of postinjury coagulopathy. METHODS: We conducted a
      retrospective study of severely injured patients entered into our trauma database
      between January and June 2008 who were at risk for postinjury coagulopathy.
      Patients needed simultaneous conventional coagulation (INR, fibrinogen, platelet
      count) and r-TEG specimens with either fresh or citrated whole blood for
      inclusion in the study. kappa-Statistics were used to determine the agreement
      between the tests in predicting hypocoagulability. McNemar's chi(2) tests were
      used to compare theoretical blood product administration between r-TEG and
      conventional coagulation tests for noncitrated specimens. Therapeutic transfusion
      triggers were: INR (>1.5) and r-TEG ACT (>125 s) for FFP administration;
      fibrinogen (<133 mg/dL) and alpha-angle (<63 degrees ) for cryoprecipitate; and
      platelet count (<100K) and maximum amplitude (MA) (<52 mm) for aphaeresis
      platelets. Statistical significance was established as P<0.05 using two-sided
      tests. RESULTS: Forty-four patients met the inclusion criteria. kappa-Values
      (correlation) were higher in noncitrated versus citrated specimens for all
      comparisons between conventional and r-TEG tests, indicating better performance
      of r-TEG with the noncitrated specimens. FFP would have been administered to
      significantly more patients based on conventional transfusion triggers (61.5% by
      INR transfusion triggers versus 26.9% by r-TEG-ACT triggers, P=0.003). There was
      no statistically significant difference in potential cryoprecipitate or
      aphaeresis platelet administration. CONCLUSION: POC r-TEG is superior when
      performed with uncitrated versus citrated whole blood for evaluation of
      postinjury coagulation status. As a real time measure of total thrombostatic
      function, our preliminary data suggest that r-TEG may effectively guide
      transfusion therapy and result in reduced FFP administration compared with
      conventional coagulation tests.

PMID- 19577247
TI  - Arginine is essential in reversing prostaglandin E(2) T-cell suppression by
      hypertonic saline.
AB  - BACKGROUND: T-cell dysfunction after trauma is characterized by decreased T-cell
      proliferation. Hypertonic saline (HS) restores T-cell proliferation by an unknown
      mechanism. Arginine and regulation of arginine metabolism plays an important role
      in normal T-cell function. We hypothesize that HS restoration of T-cell
      dysfunction is dependent on an arginine mediated mechanism. MATERIAL AND METHODS:
      Jurkat cells were cultured in both 0 mM and 1.14 mM arginine media. Cell
      proliferation was suppressed using prostaglandin E2 (PGE(2)) and treated with HS
      at 20 and 40 mM above isotonicity. Arginase activity was blocked by norNOHA. Cell
      proliferation, arginase activity, and nitrite accumulation were measured.
      RESULTS: PGE(2) caused a 15.0% inhibition of Jurkat cell proliferation compared
      with control (P<0.05). HS reversed PGE(2) suppressed Jurkat cell proliferation to
      normal. PGE(2) suppression decreased mean arginase activity (66.5+/-15
      nmol/min/mg) compared with controls (98.4+/-14 nmol/min/mg) (P<0.05). Cells
      treated with HS had higher arginase activity (123.8+/-38 nmol/min/mg) then PGE(2)
      suppressed cells and controls (P <.05). Conversely, nitrite was decreased by
      14.5% +/- 3.1% in HS treated cells compared with PGE(2) suppression (P<0.05). HS
      did not restore PGE(2) cell suppression when arginase I was blocked by norNOHA,
      nor when cells were cultured in arginine-free media. CONCLUSIONS: Arginine is
      essential in restoring Jurkat cell proliferation by HS. HS may restore T-cell
      dysfunction by increasing arginine transport and arginine metabolism by arginase
      I. HS treatment will not restore suppressed T-cell proliferation without adequate
      extracellular concentrations of arginine.

PMID- 19577249
TI  - Revisiting the role of nonanatomic resection of small (< or = 4 cm) and single
      hepatocellular carcinoma in patients with well-preserved liver function.
AB  - BACKGROUND: Anatomic resection of the liver in patients with hepatocellular
      carcinoma (HCC) is generally recommended. Several previous reports have described
      the potential superiority of anatomic resection. However, no clear evidence of
      long-term survival or other advantages compared with those achieved with limited
      resection exist. We evaluated the oncologic outcomes of nonanatomic resection
      performed as a primary treatment for small (<or=4 cm) and single HCC in patients
      with well-preserved liver function (Child-Pugh class A). MATERIALS AND METHODS:
      From March 1998 to January 2005, 353 consecutive patients underwent resection of
      HCC. Among them, 167 patients with single and small (<or=4 cm) HCC and well
      preserved liver function (Child-Pugh class A) were selected. Twenty-one patients
      (12.6%) underwent nonanatomic resection (Group NA) and 146 (82.4%) underwent
      anatomic resection (Group A). Patient factors, tumor factors, surgery factors,
      disease-free survival, and recurrence patterns were compared between the two
      groups. RESULTS: There were no significantly different preoperative clinical
      characteristics between the two groups (Group NA versus Group A). Only the
      resection margin width (0.8 +/- 0.6 cm versus 2.0 +/- 1.4 cm, P < 0.001) and
      operative time (211.9 +/- 72.9 min versus 251 +/- 80.0 min, P = 0.036) were
      significantly different between the two groups. There was no difference in
      disease-free survival between the two groups, and platelet counts of less than
      100,000/microL (P = 0.038), satellite nodules (P = 0.0164), and microscopic
      portal vein invasion (P < 0.001) were significant prognostic factors predicting
      disease-free survival in univariate analysis. Subsequent Cox-proportional hazards
      models revealed that both microscopic portal vein invasion (Exp {beta} = 3.281, P
      < 0.001) and platelet counts of less than 100,000/microL (Exp {beta} = 1.913, P =
      0.012) adversely affected disease-free survival. Nonanatomic resection did not
      have adverse effects on early recurrence compared to anatomic resection (P =
      0.805). CONCLUSION: Our study showed that nonanatomic resection has no adverse
      effects on the oncologic outcomes of single and small (<or=4 cm) HCC in patients
      with well-preserved liver function (Child-Pugh class A).

PMID- 19577248
TI  - Role of p38 MAPK in burn-induced intestinal barrier breakdown.
AB  - BACKGROUND: Severe burn results in intestinal barrier breakdown, which may lead
      to the generation of a systemic inflammatory response and distant organ injury.
      Intestinal barrier integrity is regulated, in part, by the tight junction protein
      myosin light chain kinase (MLCK). Previous studies in cell culture have shown
      that activation of p38 MAPK plays an important role in modulating intestinal
      barrier function. We hypothesized that (1) severe burn up-regulates p38 MAPK
      activation and results in increased intestinal permeability via augmented
      expression of MLCK, and (2) inhibition of p38 MAPK will prevent the burn-induced
      increase in MLCK expression, resulting in improved intestinal barrier integrity.
      MATERIALS AND METHODS: Male Balb/c mice were subjected to a 30% total body
      surface area (TBSA) full thickness steam burn, then randomized to receive an
      intraperitoneal injection of a p38 MAPK inhibitor (SB203580, 25 mg/kg) or
      vehicle. In vivo intestinal permeability to 4kDa FITC-Dextran was measured.
      Expression of phosphorylated p38 MAPK, total p38 MAPK, MLCK, and phosphorylated
      MLC from intestinal extracts was assessed by immunoblotting. RESULTS: Severe burn
      increased intestinal permeability, which was associated with activation of p38
      MAPK, and increased expression of MLCK. Treatment with SB203580 significantly
      attenuated burn-induced intestinal permeability (212 microg/mL versus 81
      microg/mL, P<0.05), and decreased expression of intestinal MLCK resulting in
      decreased phosphorylation of MLC. CONCLUSION: p38 MAPK plays an important role in
      regulating burn-induced intestinal permeability through activation of MLCK.
      Inhibition of p38 MAPK may be an important therapeutic target aimed at
      attenuating intestinal barrier breakdown by preventing the burn-induced
      alterations in tight junction proteins.

PMID- 19577250
TI  - In-hospital mortality for liver resection for metastases: a simple risk score.
AB  - BACKGROUND: Surgical management of liver metastases from various primaries is
      increasingly common. The mortality of such procedures is not well-defined.
      Accurate predictions for perioperative risk could augment decision-making.
      MATERIALS AND METHODS: The Nationwide Inpatient Sample was queried (1998-2005)
      for patient-discharges for hepatic procedures for metastases. Logistic regression
      and bootstrap methods were used to create an integer score for estimating the
      risk of in-hospital mortality using patient demographics, comorbidities,
      procedure, and hospital type. A randomly selected sample of 80% of the cohort was
      used to create the risk score, with validation of the score in the remaining 20%.
      RESULTS: For the total 50,537 patient-discharges, overall in-hospital mortality
      was 2.6%. Factors included in the model were age, sex, Charlson comorbidity
      score, procedure type, and teaching hospital status. Integer values were assigned
      for calculating an additive score. Four score groups were assembled to stratify
      risk, with a 15-fold gradient of mortality ranging from 0.9% to 14.7% (P<0.0001).
      In the derivation and the validation set, the score discriminated well, with a c
      statistic of 0.72 and 0.72, respectively. CONCLUSION: An integer-based risk score
      can be used to predict in-hospital mortality after hepatic procedure for
      metastases, and may be useful for preoperative patient counseling.

PMID- 19577251
TI  - Laparoscopic exploration of common bile duct with primary closure versus T-tube
      drainage: a randomized clinical trial.
AB  - BACKGROUND: Traditionally, the common bile duct (CBD) is closed with T-tube
      drainage after choledochotomy and removal of CBD stones. However, the insertion
      of a T-tube is not without complication and the patients have to carry it for
      several weeks before removal. In the laparoscopic era, surgery is performed with
      minimally invasive techniques in order to reduce the trauma, hasten recovery, and
      reduce the hospital stay of patients. T-tube insertion seems to negate these
      benefits. This randomized study was designed to compare the two methods applied
      after LCBDE and to determine whether primary closure can be as safe as closure
      with T-tube drainage. METHODS: From May 2000 to January 2008, 93 consecutive
      patients with common bile duct stones (CBDS) and gallbladder in situ were
      enrolled in this randomized study to undergo laparoscopic cholecystectomy with
      laparoscopic common bile duct exploration (LCBDE). Intraoperative findings,
      postoperative complications, postoperative stay, and hospital expenses were
      recorded and analyzed. RESULTS: There was no mortality in both groups. A T-tube
      was inserted in 46 patients and the CBD was closed primarily in 47. There were no
      differences in the demographic characteristics or clinical presentations between
      the two groups. Compared with the T-tube group, the operative time and
      postoperative stay were significantly shorter, the hospital expenses were
      significantly lower, and the incidences of overall postoperative complications
      and biliary complications were statistically and insignificantly lower in the
      primary closure group. CONCLUSION: LCBDE with primary closure without external
      drainage after laparoscopic choledochotomy is feasible and as safe as T-tube
      insertion.

PMID- 19577253
TI  - Constructive remodeling of biologic scaffolds is dependent on early exposure to
      physiologic bladder filling in a canine partial cystectomy model.
AB  - Biologic scaffolds composed of extracellular matrix (ECM) have been used to
      facilitate the constructive remodeling of several tissue types. Previous studies
      suggest that the ECM scaffold remodeling process is dependent on
      microenvironmental factors, including tissue-specific biomechanical loading. The
      objective of the present study was to evaluate the effects of long-term
      catheterization (LTC), with its associated inhibition of bladder filling and
      physiologic biomechanical loading, on ECM scaffold remodeling following partial
      cystectomy in a canine model. Reconstruction of the partial cystectomy site was
      performed using ECM scaffolds prepared from porcine small intestinal submucosa
      (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to
      either a long-term catheterization (LTC) group (n=5, catheterized 28 d) or a
      short-term catheterization group (STC, n=5, catheterized 24 h), and scaffold
      remodeling was assessed by histologic methods at 4 and 12 wk postoperatively. By
      4 wk, animals in the STC group showed a well-developed and highly differentiated
      urothelium, a robust vascularization network, abundant smooth muscle actin (SMA),
      and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and
      many neuronal processes associated with newly formed arterioles. In contrast, at
      4 wk the scaffolds in LTC animals were not epithelialized, and did not express
      neuronal markers. The scaffolds in the LTC group developed a dense granulation
      tissue containing SMA+, smMHC-, spindle-shaped cells that were morphologically
      and phenotypically consistent with myofibroblasts, but not smooth muscle cells.
      By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a
      constructive remodeling response, with a differentiated urothelium and islands of
      smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the
      scaffolds in LTC animals had a remodeling response more consistent with fibrosis
      even though catheters had been removed 8 wk earlier. These findings show that
      early exposure of site-appropriate mechanical loading (i.e., bladder filling)
      mediates a constructive remodeling response after ECM repair in a canine partial
      cystectomy model.

PMID- 19577252
TI  - Irrigant divalent cation concentrations influence bacterial adhesion.
AB  - BACKGROUND: Surgical wounds are frequently contaminated by microbes, but rarely
      become infected if the bacterial burden is low, and irrigation is used to reduce
      contamination. Wound fluids are low in calcium and high in magnesium. We
      hypothesized that manipulating irrigant divalent cation concentrations might
      influence bacterial adhesion. METHODS: Staphylococcus aureus, E. coli, and
      Pseudomonas aeruginosa were stained with fluorescent calcein AM before plating
      onto fibroblast monolayers, collagen I, or uncoated bacteriologic plastic. After
      1 h, wells were washed with HEPES-buffered pH-balanced sterile water without or
      with 5 mM CaCl(2), 5 mM MgCl(2), or 1 mM EDTA+EGTA, and the remaining adherent
      bacteria were assayed fluorometrically. RESULTS: Supplementing the irrigation
      with magnesium or chelators increased but calcium-supplemented irrigation reduced
      bacterial adhesion to collagen or fibroblasts. Nonspecific electrostatic
      bacterial adhesion to uncoated plastic was unaffected by calcium. CONCLUSION:
      Bacterial adhesion to mammalian cells and matrix proteins is influenced by
      divalent cations, and pathogenic bacteria may be adapted to adhere under the low
      calcium high magnesium conditions in wounds. Although these results await
      confirmation for other bacteria, and in vivo validation and safety-testing, they
      suggest that supplementing wound irrigation with 5 mM CaCl(2) may reduce
      bacterial adhesion and subsequent wound infection.

PMID- 19577254
TI  - Correlation of ischemic area and coronary flow with ameroid size in a porcine
      model.
AB  - BACKGROUND: Ameroid constriction has long been used to induce chronic hibernating
      myocardium in animal models. MATERIALS AND METHODS: Thirty-six pigs underwent
      surgical implantation of an ameroid constrictor around their left circumflex
      (LCx) coronary artery. The device had an internal diameter of 2.25 (n=9), 2.50
      (n=16), or 2.75 (n=11) mm. Thrombolysis in Myocardial Infarction (TIMI) grade
      coronary flow was assessed angiographically during device placement and on
      postoperative d 30. The ischemic and total left ventricular (LV) areas were
      measured with endocardial voltage mapping (NOGA) on d 30. RESULTS: For ameroid
      constrictor diameters of 2.25, 2.50, and 2.75 mm, the ratio of the ischemic area
      versus the total LV area averaged 24% +/- 10%, 21% +/- 6%, and 23% +/- 9%,
      respectively (P=NS). Coronary angiography revealed complete LCx occlusion in all
      animals. TIMI grade-1 flow was the statistical mode for all groups and was
      independent of constrictor diameter. Normalization of the device diameter with
      the vessel diameter did not affect the statistical results. CONCLUSIONS: For the
      range of ameroid constrictor sizes evaluated in this study, coronary flow and the
      ischemic LV area were independent of device size. The ischemic area and coronary
      flow created by ameroid constrictor placement were highly homogeneous and
      accurate for an experimental model of hibernating myocardium.

PMID- 19577255
TI  - Preservation solutions alter Mrp2-dependent bile flow in cold ischemic rat
      livers.
AB  - BACKGROUND: Previously, decreased organic anion transport through multidrug
      resistance protein 2 (Mrp2) was observed without any notable cell lysis, even
      when the livers were stored for 8 hours in University of Wisconsin solution (UW).
      The aim of this study was to examine the bile flow and its constituents, markers
      of graft dysfunction without necrosis in cold ischemic livers, using the
      following preservation media: UW, ET-Kyoto solution (ET-K) and histidine
      tryptophan-ketoglutarate solution (HTK). MATERIALS AND METHODS: Rat livers were
      stored at 4 degrees C for 8 hours in the preservation media, and reperfused to
      collect the bile and determine their constituents. Glycyrrhizin (GL) and/or
      glutathione (GSH) were added to the media as necessary. The transport efficiency
      of Mrp2 was assessed by the biliary excretion of 5-carboxyfluorescein (CF), a
      fluoroprobe excreted from Mrp2. The Intracellular distribution of Mrp2 was
      determined by immunostaining. RESULTS: Livers stored for 8 hours exhibited
      significantly decreased bile production and biliary glutathione (GSH) levels
      without notable cell lysis. CF excretion was significantly delayed in all
      solutions. However, these markers were remarkably improved by the redistribution
      of Mrp2 from the cytoplasm to the canalicular membrane, when the livers were
      exposed to UW in the presence of GL. Moreover, livers exposed to the Kyoto and
      HTK solutions increased their bile production and organic anion transport in the
      presence of GL and GSH. CONCLUSION: These results suggest that the addition of GL
      and GSH to preservation solutions improves bile production and biliary organic
      anion transport by increasing Mrp2 localization to the bile canaliculi in post
      cold ischemic livers. (248 words).

PMID- 19577256
TI  - Role of V1a receptor in AVP-induced restoration of vascular hyporeactivity and
      its relationship to MLCP-MLC20 phosphorylation pathway.
AB  - BACKGROUND: Our previous study showed that small dosage of arginine vasopressin
      (AVP) had beneficial effect on shock by improving the shock-induced vascular
      hyporeactivity. But the mechanism is not clear. The objective of the present
      study is to investigate the role of V(1a) and V(2) receptors in AVP-mediated
      restoration of hemorrhage-induced vascular hyporesponsiveness and its
      relationship to protein kinase C (PKC), myosin light chain phosphatase (MLCP),
      and myosin light chain (MLC(20)) phosphorylation signal transduction pathway.
      MATERIALS AND METHODS: We used isolated superior mesenteric artery (SMA) from
      hemorrhagic shock rats (40 mmHg for 2 hours) and 90 minutes hypoxia-treated
      vascular smooth muscle cell (VSMC) to study the effects of V(1a) and V(2)
      receptor inhibitors on AVP-mediated regulation of vascular reactivity and calcium
      sensitivity. Meanwhile the effects of AVP and V(1a) and V(2) receptor antagonists
      on the activity of MLCP and myosin light chain kinase (MLCK), and the
      phosphorylation of MLC(20), and the expression of PKC-alpha, delta, and epsilon
      isoforms were also studied. RESULTS: AVP significantly improved the reactivity of
      SMA to norepinephrine (NE) and Ca(2+) following hemorrhagic shock and increased
      the hypoxia-induced decrease of contractile response of VSMC to NE. The PKC-alpha
      and epsilon expression in particulate fractions of VSMC following hemorrhagic
      shock and hypoxia was also increased by treatment with AVP. V(1a) receptor
      inhibitor significantly antagonized these effects of AVP. AVP treatment resulted
      in a significant increase of MLC(20) phosphorylation in SMA and a significant
      decrease of MLCP activity in VSMC, which was also inhibited by V(1a) receptor
      inhibitor. CONCLUSIONS: V(1a) receptor, not V(2) receptor, played an important
      role in AVP-mediated regulation of vascular reactivity and calcium sensitivity
      following hemorrhagic shock. The mechanism is mainly through PKC-MLCP-MLC(20)
      phosphorylation calcium sensitivity pathway.

PMID- 19577257
TI  - Polyethylene glycol modified-albumin enhances the cold preservation properties of
      University of Wisconsin solution in rat liver and a hepatocyte cell line.
AB  - Liver grafts preserved in cold storage undergo changes mainly manifested by
      morphological modifications of the sinusoidal endothelium that result in poor
      graft function upon reperfusion. The present studies aimed to determine if the
      addition of polyethylene glycol-albumin to University of Wisconsin (Peg-AlbUW)
      solution ameliorates the cold preservation injuries of liver grafts. Rat livers
      were preserved cold with various preservation solutions and evaluated for weight
      changes and endothelial morphology. Solutions that preserved graft weight and
      endothelial morphology were tested in the isolated perfused rat liver model to
      assess graft function. A rat hepatocyte cell line was evaluated for both
      viability and glutathione concentrations emulating cold preservation and
      reperfusion conditions. Liver grafts preserved with Peg-AlbUW maintained their
      initial weight and showed a conserved endothelial morphology compared with liver
      grafts preserved in UW for 30 h (P<0.05). Liver grafts preserved with Peg-AlbUW
      had improved portal blood flow and bile secretion compared with liver grafts
      preserved in UW for 30 h (P<0.05). In vitro we noted comparable hepatocyte
      viability when cells were preserved in Peg-AlbUW versus UW under similar
      preservation conditions (P>0.05); glutathione concentrations (reduced and total)
      were significantly increased in hepatocytes preserved in 3% Peg-AlbUW compared
      with other preservation solutions (P<0.05). The addition of Peg-Alb to UW
      preservation solution ameliorated the cold preservation injuries of rat liver
      grafts as shown by stable liver graft weight, a better preservation of the
      endothelial morphology, improved portal vein blood flow, and increased bile
      secretion. Peg-Alb-UW solution improved the integrity of the glutathione redox
      buffer system of a hepatocyte cell line after cold storage and reperfusion.

PMID- 19577258
TI  - The effect of a hypobaric, hypoxic environment on acute skeletal muscle edema
      after ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Clinicians have postulated that decreased atmospheric pressure during
      air evacuation exacerbates muscle edema and necrosis in injured limbs. The
      present study investigated whether the mild hypobaric, hypoxic conditions of
      simulated flight during muscle reperfusion worsened muscle edema and muscle
      injury in an established animal model. METHODS: Twenty male Sprague-Dawley rats
      underwent tourniquet-induced hind limb ischemia for 2h. After removal of the
      tourniquet, rats were divided into two groups (n=10/group), and exposed to either
      (1) hypobaric, hypoxic conditions (HB) of 522 mm Hg (simulating 10,000 feet, the
      upper limit of normal aircraft cabin pressure), or (2) normobaric, normoxic
      conditions (NB) of 760 mm Hg (sea level), for 6h. Muscle wet weight, muscle
      dry:wet weight ratios, viability, and routine histology were measured on the
      gastrocnemius and tibialis anterior muscles. Blood samples were analyzed for
      percentage hematocrit, leukocyte count, and coagulation status. RESULTS: Ischemia
      resulted in significant edema in both groups (P<0.05). Normobaric normoxia caused
      greater edema in the gastrocnemius compared with hypobaric hypoxia; the tibialis
      anterior was not significantly different between groups. The decrease in body
      weight for NB and HB was 3.4+/-1.4 and 10.7+/-1.2g, respectively (P<0.05).
      Hematocrit was 44.7+/-0.5 and 42.6+/-0.6 (P<0.05). CONCLUSIONS: The hypobaric,
      hypoxic conditions of simulated medical air evacuation were not associated with
      increased muscle edema following 2h of ischemic injury. This suggests that other
      factors, such as resuscitation, may be the cause of muscle edema in flight
      evacuated patients.

PMID- 19577259
TI  - Interleukin-17F-induced pulmonary microvascular endothelial monolayer
      hyperpermeability via the protein kinase C pathway.
AB  - BACKGROUND: Interleukin (IL)-17F is involved in lung inflammation, but the effect
      of IL-17F on endothelial permeability and its signaling pathway remain ill
      defined. The current study sought to investigate the effect of IL-17F on
      endothelium and assess the role of protein kinase C (PKC) and src-suppressed C
      kinase substrate (SSeCKS) in this process. METHODS: Rat pulmonary microvascular
      endothelial monolayers were constructed to determine changes of permeability as
      measured by means of FITC-dextran and Hank's solution flux across monolayers and
      transendothelial electrical resistance with or without IL-17F and PKC inhibitors.
      Additional monolayers were stained using FITC-phalloidin for filamentous actin (F
      actin). The gene expression of SSeCKS was analyzed by the reverse transcription
      polymerase chains. Alterations of SSeCKS protein were investigated by
      immunoblotting and immunoprecipitation. RESULTS: IL-17F increased endothelial
      monolayer permeability in a dose- and time-dependent manner. F-actin staining
      revealed that permeability changes were accompanied by reorganization of
      cytoskeleton. In the presence of PKC inhibitors, the IL-17F-induced
      hyperpermeability and reorganization of F-actin were attenuated. The gene and
      protein expression of SSeCKS were conspicuously elevated after IL-17F challenge.
      The process of SSeCKS phosphorylation followed a time course that mirrored the
      time course of hyperpermeability induced by IL-17F. IL-17F-induced SSeCKS
      phosphorylation was abrogated after PKC inhibitors pretreatment. The
      translocation of SSeCKS from the cytosol to the membrane and a significant
      increase in the SSeCKS association with the cytoskeleton were found after IL-17F
      treatment. CONCLUSIONS: IL-17F is an important mediator of increased endothelial
      permeability. PKC and SSeCKS are integral signaling components essential for IL
      17F-induced hyperpermeability.

PMID- 19577261
TI  - Outcomes of coronary surgery at a Veterans Affairs hospital versus other
      hospitals.
AB  - BACKGROUND: The aim of this study was to compare outcomes of coronary artery
      bypass grafting (CABG) operations at a VA hospital and non-VA hospitals.
      MATERIALS AND METHODS: Using the 2004 Nationwide Inpatient Sample database, we
      identified 48,669 discharge records of patients who underwent CABG in non-VA
      hospitals and compared these patients' outcomes with those of 688 patients who
      underwent CABG at our VA hospital from 2002 to 2006. Student t- tests and chi(2)
      tests were used to identify significant intergroup differences. RESULTS: The VA
      patients were slightly younger than the non-VA patients (62 +/- 8 versus 66 +/-
      11 y, P < 0.0001). The VA patients also had a higher prevalence of prior
      myocardial infarction (60.6% versus 34.6%), congestive heart failure (38.2%
      versus 22.1%), peripheral vascular disease (25.9% versus 7.2%), cerebral vascular
      disease (23.4% versus 5.9%), chronic obstructive pulmonary disease (32.3% versus
      16.6%), and diabetes (41.7% versus 29.7%) (P < 0.0001 for all). Nonetheless, the
      in-hospital mortality rate was significantly lower in VA patients than in non-VA
      patients (1.6% versus 3.0%, P = 0.03). CONCLUSIONS: Despite the higher prevalence
      of comorbidities, patients who underwent CABG at a VA hospital had a
      significantly lower mortality rate than CABG patients in non-VA hospitals.

PMID- 19577260
TI  - The role of VEGF pathways in human physiologic and pathologic angiogenesis.
AB  - BACKGROUND: In preclinical models, VEGF is a potent stimulant of both physiologic
      and pathologic angiogenesis. Conversely, anti-VEGF regimens have successfully
      inhibited angiogenesis both in vitro and in vivo. We hypothesized that VEGF would
      stimulate both physiologic and pathologic angiogenesis in a human-based fibrin
      thrombin clot angiogenesis assay. We further speculated that anti-VEGF regimens
      would inhibit angiogenesis in this assay. METHODS: To test these hypotheses,
      discs of human placental veins (physiologic model) and fragments of human tumors
      (pathologic model) were embedded in fibrin-thrombin clots and treated with either
      VEGF-A165 (VEGF) or anti-VEGF pathway reagents including bevacizumab, IMC-18F1,
      IMC-1121, and PTK787 (n=30 wells per treatment group, multiple concentrations
      tested in each specimen). Angiogenic responses were assessed visually using a
      previously validated grading scheme. The percent of tissue explants that
      developed angiogenic invasion into the clot (% I) as well as the extent of
      angiogenic growth (AI) via a semi-quantitative scale were assessed at set
      intervals. RESULTS: VEGF failed to stimulate angiogenesis in both the physiologic
      and the pathologic model. While anti-VEGF reagents that targeted only one element
      of the VEGF pathway failed to consistently inhibit angiogenesis, PTK787, a
      receptor tyrosine kinase inhibitor that targets multiple VEGF and non-VEGF
      receptors, profoundly inhibited both physiologic and pathologic angiogenesis.
      CONCLUSION: These results suggest that VEGF-related pathways may not be solely
      responsible for stimulating angiogenesis in humans. Targeting the VEGF pathway in
      combination with elements of other growth factor pathways may provide a more
      effective means of inhibiting angiogenesis than targeting VEGF alone.

PMID- 19577262
TI  - Intractable hiccup caused by medulla oblongata lesions: a study of an autopsy
      patient with possible neuromyelitis optica.
AB  - We report the first autopsy verification of medulla oblongata lesions involving
      bilateral nucleus tractus solitarius (NTS) as a cause of intractable hiccup in an
      autopsy patient. The female patient first developed pain and weakness in the
      lower limbs and urinary incontinence at age 48, and was given a diagnosis of
      myelitis. Intractable hiccup was accompanied by urinary retention on the third
      attack. She died of respiratory failure when the fifth attack occurred at age 51.
      Autopsy disclosed severe involvement of the medulla oblongata and entire spinal
      cord. Optic nerve lesions were also identified unexpectedly. Dual involvement of
      the optic nerve and spinal cord, necrotic spinal cord lesions involving not only
      myelin but also neurons and axon, and marked extension of the spinal cord lesions
      in both the longitudinal and transverse directions suggested the diagnosis of
      neuromyelitis optica rather than multiple sclerosis. Although animal experiments
      have shown that NTS is a critical structure in the hiccup reflex, we demonstrated
      for the first time the involvement of the NTS in an autopsy patient with
      intractable hiccup.

PMID- 19577263
TI  - [Clarifications about the diagnosis of pulmonary embolism].

PMID- 19577264
TI  - [Primary pulmonary meningioma].

PMID- 19577265
TI  - Resistance mechanisms and farm-level distribution of fecal Escherichia coli
      isolates resistant to extended-spectrum cephalosporins in pigs in Spain.
AB  - INTRODUCTION: Fecal Escherichia coli isolates showing a phenotype of reduced
      susceptibility or resistance to extended-spectrum cephalosporins are common among
      pigs in Spain. The aim of this study was to describe the main beta-lactam
      resistance mechanisms carried by these strains and their distribution at farm
      level. MATERIALS AND METHODS: Twenty-nine E. coli isolates showing reduced
      susceptibility or resistance to extended-spectrum cephalosporins were collected
      from a sampling frame of 80 pig farms distributed over 13 Spanish provinces. The
      survey was carried out at the slaughterhouse level in 2004. RESULTS: Of the 29
      isolates, 21 (72%) met the criteria for a positive phenotypic confirmatory test
      for extended-spectrum beta-lactamases (ESBL). The following ESBLs were detected:
      SHV-12 (12 isolates, 41%), CTX-M-1 (three isolates, 10%), CTX-M-9 (three
      isolates, 10%), and CTX-M-14 (three isolates, 10%). The remaining eight isolates
      (28%) were phenotypically non-ESBL, with seven of them (24%) showing mutations on
      the chromosomal ampC gene promoter at positions -42 (C-->T), -18 (G-->A), -1 (C-
      >T), and +58 (C-->T). A multiplex PCR for detection of plasmidic class C beta
      lactamases was negative for all isolates. CONCLUSION: Different ESBLs and other
      mechanisms linked to extended-spectrum cephalosporin resistance are widely
      distributed among fecal E. coli from slaughter pigs in Spain.

PMID- 19577267
TI  - Removal of emerging contaminants of concern by alternative adsorbents.
AB  - The effective removal of emerging contaminants of concern (ECCs) such as
      endocrine-disrupting chemicals, pharmaceutically active compounds, personal care
      products, and flame retardants is a desirable water treatment goal. In this
      study, one activated carbon, one carbonaceous resin, and two high-silica zeolites
      were studied to evaluate their effectiveness for the removal of an ECC mixture
      from lake water. Adsorption isotherm experiments were performed with a mixture of
      28 ECCs at environmentally relevant concentrations ( approximately 200-900 ng/L).
      Among the tested adsorbents, activated carbon was the most effective, and
      activated carbon doses typically used for taste and odor control in drinking
      water (<10 mg/L) were sufficient to achieve a 2-log removal for most of the
      tested ECCs. The carbonaceous resin was less effective than the activated carbon
      because this adsorbent had a smaller volume of pores in the size range required
      for the adsorption of many ECCs ( approximately 6-9A). For the removal of ECC
      mixture constituents, zeolites were less effective than the carbonaceous
      adsorbents. Because zeolites contain pores of uniform size and shape, a few of
      the tested ECCs with matching pore size/shape requirements were well removed, but
      the adsorptive removal of others was negligible, even at zeolite doses of 100
      mg/L. The results of this study demonstrate that effective adsorbents for the
      removal of a broad spectrum of ECCs from water should exhibit heterogeneity in
      pore size and shape and a large pore volume in the 6-9A size range.

PMID- 19577268
TI  - The extended Kalman filter for forecast of algal bloom dynamics.
AB  - A deterministic ecosystem model is combined with an extended Kalman filter (EKF)
      to produce short term forecasts of algal bloom and dissolved oxygen dynamics in a
      marine fish culture zone (FCZ). The weakly flushed FCZ is modelled as a well
      mixed system; the tidal exchange with the outer bay is lumped into a flushing
      rate that is numerically determined from a three-dimensional hydrodynamic model.
      The ecosystem model incorporates phytoplankton growth kinetics, nutrient uptake,
      photosynthetic production, nutrient sources from organic fish farm loads, and
      nutrient exchange with a sediment bed layer. High frequency field observations of
      chlorophyll, dissolved oxygen (DO) and hydro-meteorological parameters (sampling
      interval Deltat=1 day, 2h, 1h, respectively) and bi-weekly nutrient data are
      assimilated into the model to produce the combined state estimate accounting for
      the uncertainties. In addition to the water quality state variables, the EKF
      incorporates dynamic estimation of algal growth rate and settling velocity. The
      effectiveness of the EKF data assimilation is studied for a wide range of
      sampling intervals and prediction lead-times. The chlorophyll and dissolved
      oxygen estimated by the EKF are compared with field data of seven algal bloom
      events observed at Lamma Island, Hong Kong. The results show that the EKF
      estimate well captures the nonlinear error evolution in time; the chlorophyll
      level can be satisfactorily predicted by the filtered model estimate with a mean
      absolute error of around 1-2 microg/L. Predictions with 1-2 day lead-time are
      highly correlated with the observations (r=0.7-0.9); the correlation stays at a
      high level for a lead-time of 3 days (r=0.6-0.7). Estimated algal growth and
      settling rates are in accord with field observations; the more frequent DO data
      can compensate for less frequent algal biomass measurements. The present study is
      the first time the EKF is successfully applied to forecast an entire algal bloom
      cycle, suggesting the possibility of using EKF for real time forecast of algal
      bloom dynamics.

PMID- 19577269
TI  - Application of ultrasound-assisted emulsification-micro-extraction for the
      analysis of organochlorine pesticides in waters.
AB  - Ultrasound-assisted emulsification-micro-extraction (USAEME) procedure was
      developed for the determination of different organochlorine pesticides (OCPs) in
      water samples by gas chromatography with mu-electron capture detection (GC
      microECD). After the determination of the most suitable extraction solvent and
      its volume, parameters such as extraction time, centrifugation time and ionic
      strength of the sample were optimized by using a 2(3) factorial experimental
      design. For 10 mL of water sample, the optimized USAEME procedure used 200 microL
      of chloroform as extraction solvent, 15 min of extraction without ionic strength
      adjustment at 25 degrees C and 5 min of centrifugation at 4000 rpm. Limits of
      detection ranged from 0.002 to 0.016 microg L(-1). Mean recoveries of OCPs from
      fortified water samples are over 96% for three different fortification levels
      between 0.5 and 5 microg L(-1) and relative standard deviations of the recoveries
      are below 9%. The developed procedure was successfully applied for real water
      samples (i.e., tap water, well water, surface (lake) water, domestic and
      industrial wastewater). Performance of the procedure was compared with those
      involving traditional liquid-liquid extraction and solid-phase extraction. The
      result demonstrates that the USAEME procedure is viable, rapid and easy to use
      for analysis of OCPs in water samples.

PMID- 19577266
TI  - A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in
      Baka pygmies.
AB  - The global acquired immunodeficiency syndrome (AIDS) pandemic is thought to have
      arisen by the transmission of human immunodeficiency virus (HIV-1)-like viruses
      from chimpanzees in southeastern Cameroon to humans. TRIM5alpha is a restriction
      factor that can decrease the susceptibility of cells of particular mammalian
      species to retrovirus infection. A survey of TRIM5 genes in 127 indigenous
      individuals from southeastern Cameroon revealed that approximately 4% of the Baka
      pygmies studied were heterozygous for a rare variant with a stop codon in exon 8.
      The predicted product of this allele, TRIM5 R332X, is truncated in the
      functionally important B30.2(SPRY) domain, does not restrict retrovirus
      infection, and acts as a dominant-negative inhibitor of wild-type human
      TRIM5alpha. Thus, some indigenous African forest dwellers potentially exhibit
      diminished TRIM5alpha function; such genetic factors, along with the high
      frequency of exposure to chimpanzee body fluids, may have predisposed to the
      initial cross-species transmission of HIV-1-like viruses.

PMID- 19577270
TI  - Impact of nitrate addition on biofilm properties and activities in rising main
      sewers.
AB  - Anaerobic sewer biofilm is a composite of many different microbial populations,
      including sulfate reducing bacteria (SRB), methanogens and heterotrophic
      bacteria. Nitrate addition to sewers in an attempt to control hydrogen sulfide
      concentrations affects the behaviour of these populations, which in turn impacts
      on wastewater characteristics. Experiments were carried out on a laboratory
      reactor system simulating a rising main to determine the impact of nitrate
      addition on the microbial activities of anaerobic sewer biofilm. Nitrate was
      added to the start of the rising main during sewage pump cycles at a
      concentration of 30 mg-N L(-1) for over 5 months. While it reduced sulfide levels
      at the outlet of the system by 66%, nitrate was not toxic or inhibitory to SRB
      activity and did not affect the dominant SRB populations in the biofilm. Long
      term nitrate addition in fact stimulated additional SRB activity in downstream
      biofilm. Nitrate addition also stimulated the activity of nitrate reducing,
      sulfide oxidizing bacteria that appeared to be primarily responsible for the
      prevention of sulfide build up in the wastewater in the presence of nitrate. A
      short adaptation period of three to four nitrate exposure events (approximately
      10 h) was required to stimulate biological sulfide oxidation, beyond which no
      sulfide accumulation was observed under anoxic conditions. Nitrate addition
      effectively controlled methane concentrations in the wastewater. The nitrate
      uptake rate of the biofilm increased with repeated exposure to nitrate, which in
      turn increased the consumption of biodegradable COD in the wastewater. These
      results provide a comprehensive understanding of the impact of nitrate addition
      on wastewater composition and sewer biofilm microbial activities, which will
      facilitate optimization of nitrate dosing for effective sulfide control in rising
      main sewers.

PMID- 19577271
TI  - Effect of Fenton's oxidation on the particle size distribution of organic carbon
      in olive mill wastewater.
AB  - The study evaluated the effect of Fenton's oxidation on the particle size
      distribution (PSD) of significant parameters reflecting the organic carbon
      content of olive oil mill wastewater (OMW). The organic carbon content of the
      studied OMW was characterized by a COD level of around 40,000 mg/L, with 13,500
      mg/L of TOC and 1670 mg/L of total phenols. The corresponding antioxidant
      activity (AOA) was determined as 33,400mg/L. PSD of the selected organic carbon
      parameters was investigated using a sequential filtration/ultrafiltration
      procedure. COD fractionation based on PSD revealed two major components, a
      soluble fraction below 2 nm and a particulate fraction above 1600 nm representing
      49% and 20% of the total COD, respectively. The remaining COD was distributed in
      the colloidal and supracolloidal zones. The PSD of TOC, total phenols and AOA
      exhibited similar profiles with peaks at the two ends of the studied size range.
      Overall COD removals achieved via Fenton's oxidation both at pH=3.0 and pH=4.6
      (the original pH of the OMW) remained in the range of 40-50%. As anticipated, the
      effect of Fenton's treatment was more pronounced in the soluble size range.
      Fenton's oxidation at pH=3.0 resulted in 46% and 63% removals for total phenols
      and AOA, respectively. The results obtained indicated that Fenton's process could
      only be useful as an alternative preliminary treatment option of the required
      full treatment scheme that could involve a sequence of filtration, oxidation
      and/or biological treatment steps.

PMID- 19577272
TI  - Solar treatment of cork boiling and bleaching wastewaters in a pilot plant.
AB  - This paper reports on cork boiling and bleaching wastewaters treatment by solar
      photocatalytic processes, TiO(2)/UV and Fe(2+)/H(2)O(2)/UV (TiO(2)-only for
      bleaching wastewater), in a pilot plant with compound parabolic collectors. The
      photo-Fenton reaction (k=0.12L/kJ(UV), r(0)=59.4 mg/kJ(UV)) is much more
      efficient that TiO(2) photocatalysis and TiO(2)+S(2)O(8)(2-) (k=0.0024 L/kJ(UV),
      r(0)=1.36 mg/kJ(UV)), leading to 94% mineralization of the bleaching wastewater
      after 31.5 kJ(UV)/L, consuming 77.1mM of H(2)O(2) (3.0 mmol/kJ(UV)) and using 20
      mg/L of iron. For the cork boiling wastewater, after a slow initial reaction
      rate, the DOC degradation curve shows a first-order kinetics behaviour (k=0.015
      L/kJ(UV), r(0)=20.8 mg/kJ(UV)) until 173 kJ(UV)/L ( approximately 300 mgC/L).
      According to the average oxidation state (AOS), toxicity profiles, respirometry
      and kinetic results obtained in two solar CPCs plants, the optimal energy dose
      estimated for phototreatment to reach a biodegradable effluent is 15 kJ(UV)/L and
      114 kJ(UV)/L, consuming 33 mM and 151 mM of
      H(2)OT:/PGN/ELSEVIER/WR/web/00007490/(2), achieving almost 49% and 48%
      mineralization of the wastewaters, respectively for the cork bleaching and
      boiling wastewaters.

PMID- 19577273
TI  - Impact of glyphosate on the development, fertility and demography of Chrysoperla
      externa (Neuroptera: Chrysopidae): ecological approach.
AB  - Few ecotoxicological studies have used life table analysis to evaluate the
      toxicity of pesticides on beneficial organisms. This study is the first report of
      the effect of the herbicide glyphosate on a predator insect, Chrysoperla externa,
      using a demographic approach. This predator is associated to soybean pests and
      has a potential role as a biological control agent in the Neotropical Region. The
      objective of this work was to evaluate the side-effects of glyphosate on the
      development, fertility and demography of C. externa, treated orally by ingestion
      of glyphosate-dipped eggs of Sitotroga cerealella in laboratory conditions. The
      data were analyzed using the age-stage, two-sex life table. Development from
      third larval instar to pupae and adult longevity were shorter in glyphosate
      treatment than in the control. Adult pre-reproductive period was longer in
      glyphosate-treatment than in the control. Fecundity and fertility were deeply
      reduced, as well, being fertility greater affected. A high important reduction
      was registered in all population parameters. Most eggs from glyphosate-treated
      cohort looked abnormal, smaller than control, dehydrated and became black 2d
      after oviposition. In addition, adults developed tumours in the abdomen region at
      20d after emergence, being the effect more drastic in females than males. It is
      beyond the scope of our study to speculate on the effects of this herbicide on C.
      externa field populations. However, it seems likely that populations under
      continuous use of glyphosate would be exposed at greater detrimental effects in
      the long term.

PMID- 19577274
TI  - Phosphorus fractionation in membrane-assisted biological nutrient removal
      processes.
AB  - A comparison between a patented novel membrane bioreactor (NMBR) and conventional
      University of Cape Town adapted MBR (UMBR) was conducted using two different
      municipal wastewaters at a total bioreactor hydraulic retention time of 6h and
      sludge retention time of 10d. Total nitrogen removal efficiencies were 73-80% and
      70-77% for the NMBR and UMBR, respectively, with 1-1.7 mgL(-1) lower effluent
      nitrates in the NMBR. The average effluent P in the NMBR and UMBR were 0.5 and
      0.8 mgL(-1), respectively. P uptake by denitrifying phosphate accumulating
      organisms (DPAO) accounted for 37-40% of the total uptake in both systems and
      DPAOs were 40% of PAO. Sludge P fractionation substantiated that poly-P content
      increased from 27-37% to 57-59% of the total phosphorus, with P increasing from
      around 3% to 6% by weight upon the supplementation of the wastewater volatile
      fatty acids.

PMID- 19577275
TI  - DDT polluted meltwater affects reproduction in the mussel Dreissena polymorpha.
AB  - The zebra mussel Dreissena polymorpha was used to follow the recently reported
      DDT pollution of Lake Iseo (N. Italy). Histopathological analyses were performed
      on mussels sampled from March 2005 to April 2006, when high DDT levels were
      found, and results were compared to those from mussels sampled in 2001/2002,
      before the pollution event. During the 2005/2006 reproductive season, the first
      male gamete release happened one month later than the onset of spawning in
      females who showed a high number of specimens with degenerating oocytes, despite
      a regular pattern of gametogenesis. These results indicated a disrupting action
      of DDT on the mechanisms involved in sperm release, and a disturbance in the
      gametogenic phases of the ovary. Pathological pictures in the digestive gland of
      many mussels from both 2001/2002 and 2005/2006 have also been observed, but DDT
      pollution is unable to explain the presence of pathological fields in mussels
      during 2001/2002, for which a previously reported contamination seems to be the
      main cause. A possible role of DDT in skewing the sex ratio towards a
      predominance of females was also discussed, considering the high number of
      females sampled in 2005/2006.

PMID- 19577276
TI  - Experimental and modeling study of the effects of multicomponent gas additives on
      selective non-catalytic reduction process.
AB  - The influence of multicomponent additives on NO reduction by selective non
      catalytic reduction process has been investigated experimentally in an
      electricity-heated tube reactor. The multicomponent additives are composed of two
      species of CO, CH(4) and H(2), and the molar ratio of their two components varies
      from 1/3 to 3/1. The results show that all the investigated additives could
      decrease the optimal temperature for NO reduction effectively, but the
      contributions of their components are different. The performance of
      multicomponent additive composed of CO and CH(4) depends mainly on CH(4)
      component. The function of CO component is shifting the temperature window for NO
      reduction to lower temperature slightly and narrowing the temperature window a
      little. The temperature window with multicomponent additive composed of H(2) and
      CH(4) is distinct from that with its each component, so both H(2) and CH(4)
      component make important contributions. While the fraction of CO is no more than
      that of H(2) in multicomponent additives composed of them, the performance of
      multicomponent additives is dominated by H(2) component; while the fraction of CO
      becomes larger, the influence of CO component becomes notable. Qualitatively the
      modeling results using a detailed chemical kinetic mechanism exhibit the same
      characteristics of the temperature window shift as observed experimentally. By
      reaction mechanism analysis, the distinct influences of CO, CH(4) or H(2)
      component on the property of multicomponent additive are mainly caused by the
      different production rates of (*)OH radical in their own oxidation process.

PMID- 19577277
TI  - Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in
      ovarian cancer.
AB  - OBJECTIVE: Intraperitoneal (IP) chemotherapy has gained enthusiasm in the
      treatment of ovarian cancer. Despite having a better survival advantage than
      intravenous (IV) chemotherapy, IP chemotherapy still poses significant morbidity
      and complications. Identifying the subset of patients who could best benefit from
      IP chemotherapy, and those who would least benefit from this treatment, thus
      avoiding potential complications, is critical. METHODS: Between January 2001 and
      December 2007, 367 patients with stage III epithelial ovarian cancer underwent
      randomized trial for IP/IV chemotherapy were recruited to construct a nomogram,
      which is a graphical representation of Cox proportional hazards model adopting
      six weighted risk factors including age, CA125, IP/IV delivery, stage, histology,
      and upper abdominal metastases. The nomogram was internally validated for
      discrimination and calibration. The concordance index was used for quantifying
      the predictive ability of overall survival with bootstrapping to correct for
      bias. RESULTS: The cycles of completed IP chemotherapy had an impact on overall
      survival (> or =5 vs. < or =4 cycles, P=0.02). A nomogram for predicting median
      survival and 5-year survival probability was constructed with a concordance index
      of 0.72. Upper abdominal tumor metastases (P<0.001) and colon resection (P=0.02)
      predicted increased chances for early discontinuation of IP chemotherapy.
      CONCLUSIONS: At least five IP cycles are needed to achieve better survival.
      Nomogram can help to identify the subset of patients who can least benefit from
      IP chemotherapy, thus avoiding potential IP complications and help to facilitate
      discussion between patient and physician, risk stratification, and help to guide
      clinical care.

PMID- 19577278
TI  - Plasma calprotectin concentrations in women with endometrial carcinoma.
AB  - OBJECTIVES: There is a lack of circulating markers to predict disease outcome,
      therapy effect and monitoring for disease recurrence in endometrial cancer. The
      aim of this study was to explore whether plasma concentration of the inflammatory
      marker calprotectin is elevated in endometrial cancer and related to clinical
      parameters. METHODS: Calprotectin in EDTA-plasma samples from women with primary
      endometrial carcinoma (n=194), from healthy premenopausal (n=20) and
      postmenopausal (n=20) women was analyzed with ELISA. RESULTS: Median plasma
      calprotectin concentration was elevated in the patient group of endometrial
      cancer (3415 microg/L) as compared to the healthy premenopausal (832 microg/L)
      and postmenopausal groups (868 microg/L), both p<0.001. Also, median calprotectin
      concentration was elevated in the endometrial cancer group as compared to women
      with invasive ovarian cancer, borderline ovarian tumor and benign ovarian tumors.
      Calprotectin plasma concentration correlated significantly with poor survival and
      high FIGO stage in endometrial carcinoma. CONCLUSION: Calprotectin is elevated in
      plasma of women with endometrial carcinoma. Further studies are warranted to
      assess its possible value as a clinical tool for evaluating disease progression
      and relapse, as well as in monitoring treatment response.

PMID- 19577279
TI  - Letter to the Editor Re. Paper: "the role of lymphadenectomy in the management of
      preoperative grade 1 endometrial carcinoma".

PMID- 19577280
TI  - Tamoxifen and the risk of ovarian cancer in BRCA1 mutation carriers.
AB  - OBJECTIVE: BRCA1 mutation carriers have a high rate of both breast and ovarian
      cancer. Tamoxifen is a selective estrogen receptor modulator (SERM), which is
      used for the treatment of primary breast cancer and for the prevention of
      contralateral breast cancer. Our objective is to assess if tamoxifen treatment is
      associated with an increase in the subsequent risk of ovarian cancer among women
      with a BRCA1 mutation. METHODS: A matched case-control study was performed. Cases
      were 154 women with ovarian cancer and a previous history of breast cancer.
      Controls were 560 women with no ovarian cancer and a history of breast cancer.
      All cases and controls carry a deleterious BRCA1 mutation. Cases and controls
      were matched for year of birth, age at diagnosis of breast cancer and country of
      residence. The effect of tamoxifen treatment on the risk of subsequent ovarian
      cancer was estimated using conditional logistic regression. RESULTS: The
      unadjusted odds ratio for ovarian cancer, given previous tamoxifen treatment was
      0.89 (95% CI 0.54-1.49, p=0.66). After adjusting for other treatments, the odds
      ratio was 0.78 (95% CI 0.46-1.33, p=0.36). CONCLUSION: Tamoxifen treatment for
      breast cancer does not appear to increase the risk of ovarian cancer in BRCA1
      mutation carriers.

PMID- 19577281
TI  - Development of a novel peptide microarray for large-scale epitope mapping of food
      allergens.
AB  - BACKGROUND: The peptide microarray is a novel assay that facilitates high
      throughput screening of peptides with a small quantity of sample. OBJECTIVE: We
      sought to use overlapping peptides of milk allergenic proteins as a model system
      to establish a reliable and sensitive peptide microarray-based immunoassay for
      large-scale epitope mapping of food allergens. METHODS: A milk peptide microarray
      was developed by using commercially synthesized peptides (20-mers, 3 offset)
      covering the primary sequences of alpha(s1)-casein, alpha(s2)-casein, beta
      casein, kappa-casein, and beta-lactoglobulin. Conditions for printing and
      immunolabeling were optimized using a serum pool of 5 patients with milk allergy.
      Reproducibility of the milk peptide microarray was evaluated using replicate
      arrays immunolabeled with the serum pool, whereas specificity and sensitivity
      were assessed by using serial dilution of the serum pool and a peptide inhibition
      assay. RESULTS: Our results show that epitopes identified by the peptide
      microarray were mostly consistent with those identified previously by SPOT
      membrane technology, but with specific binding to a few newly identified epitopes
      of milk allergens. Data from replicate arrays were reproducible (r > or = 0.92)
      regardless of printing lots, immunolabeling, and serum pool batches. Using the
      serially diluted serum pool, we confirmed that IgE antibody binding detected in
      the array was specific. Peptide inhibition of IgE binding to the same peptide and
      overlapping peptides further confirmed the specificity of the array. CONCLUSION:
      A reliable peptide microarray was established for large-scale IgE epitope mapping
      of milk allergens, and this robust technology could be applied for epitope
      mapping of other food allergens.

PMID- 19577282
TI  - Major increase in allergic sensitization in schoolchildren from 1996 to 2006 in
      northern Sweden.
AB  - BACKGROUND: Time trends for allergic sensitization are poorly known. OBJECTIVE:
      To compare the trends in prevalence of allergic sensitization and associated risk
      factors in children. METHODS: Two cohorts of children (age 7-8 years) were
      invited for skin prick tests (SPTs) 10 years apart, 1996 and 2006. The
      participation rates were 2148 (88%) and 1700 (90%), respectively. The methods
      were identical, and 10 common airborne allergens were used. An expanded
      International Study of Allergy and Asthma in Children questionnaire about
      symptoms and possible risk factors for allergic conditions was completed by the
      parents. RESULTS: The prevalence of any positive SPT increased from 21% in 1996
      to 30% in 2006 (P < .001). The pattern of sensitization remained similar, and
      sensitization to cat was most common both years, 13% and 19%, respectively.
      Sensitization to mites and mold was uncommon in both surveys. A family history of
      allergy was a significant risk factor for a positive SPT both years (odds ratio,
      1.7). Factors that in 1996 had a protective effect, such as rural living and
      having several siblings, had lost this effect in 2006. The prevalence of most
      risk factors remained similar, but respiratory infections and smoking among
      parents decreased significantly. During the same period, there was no significant
      increase in the prevalence of current wheeze (11.9% to 12.4%, P = .636) or
      symptoms of rhinitis or eczema. CONCLUSION: The prevalence of allergic
      sensitization increased significantly from 1996 to 2006, whereas no increase in
      clinical symptoms was found. The parallel decrease in parental smoking and
      respiratory infections indicate a different influence of environmental factors on
      allergic sensitization and clinical symptoms, respectively.

PMID- 19577283
TI  - Clinical efficacy and immune regulation with peanut oral immunotherapy.
AB  - BACKGROUND: Oral immunotherapy (OIT) has been thought to induce clinical
      desensitization to allergenic foods, but trials coupling the clinical response
      and immunologic effects of peanut OIT have not been reported. OBJECTIVE: The
      study objective was to investigate the clinical efficacy and immunologic changes
      associated with OIT. METHODS: Children with peanut allergy underwent an OIT
      protocol including initial day escalation, buildup, and maintenance phases, and
      then oral food challenge. Clinical response and immunologic changes were
      evaluated. RESULTS: Of 29 subjects who completed the protocol, 27 ingested 3.9 g
      peanut protein during food challenge. Most symptoms noted during OIT resolved
      spontaneously or with antihistamines. By 6 months, titrated skin prick tests and
      activation of basophils significantly declined. Peanut-specific IgE decreased by
      12 to 18 months, whereas IgG(4) increased significantly. Serum factors inhibited
      IgE-peanut complex formation in an IgE-facilitated allergen binding assay.
      Secretion of IL-10, IL-5, IFN-gamma, and TNF-alpha from PBMCs increased over a
      period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells
      increased until 12 months and decreased thereafter. In addition, T-cell
      microarrays showed downregulation of genes in apoptotic pathways. CONCLUSION:
      Oral immunotherapy induces clinical desensitization to peanut, with significant
      longer-term humoral and cellular changes. Microarray data suggest a novel role
      for apoptosis in OIT.

PMID- 19577285
TI  - Inhibition of S100A11 gene expression impairs keratinocyte response against
      vaccinia virus through downregulation of the IL-10 receptor 2 chain.
AB  - BACKGROUND: The mechanism that predisposes patients with atopic dermatitis (AD)
      to disseminated vaccinia viral (VV) skin infection after smallpox vaccination is
      unknown. We have demonstrated that expression of S100A11, a calcium-binding
      protein involved in keratinocyte differentiation, is downregulated in AD.
      OBJECTIVE: We investigated whether inhibiting expression of S100A11 increased VV
      replication in human keratinocytes and the mechanism by which S100A11 affects the
      innate immune response of keratinocytes. METHODS: Small interfering RNA duplexes
      were used to reduce gene expression of S100A11 in keratinocytes. VV replication
      was evaluated by real-time PCR and viral plaque assay. VV cytopathic effect was
      assessed by crystal violet staining. Affymetrix GeneChip assay was used to
      compare gene expression profiles. Real time PCR, Western blotting, and
      immunohistochemistry staining assay were used to evaluate gene expression in
      keratinocytes and AD skin biopsies. RESULTS: Keratinocytes with deficient S100A11
      expression supported increased VV replication and manifested augmented VV
      cytopathic effects. Gene microarray analysis revealed that the IL-10 receptor 2
      chain (IL-10R2), which binds IFN-lambdas, was downregulated by 2.26-fold in
      S100A11-silenced keratinocytes. IL-10R2 expression was found to be decreased in
      skin biopsies from patients with acute AD (mean, 25.21 +/- 5.25; n = 20) compared
      with skin from normal healthy subjects (mean, 137.1 +/- 34.46; n = 19; P < .01).
      Furthermore, deficient S100A11 gene expression significantly impaired IL-29 (IFN
      lambda1) responsiveness (2' 5'-oligoadenylate synthetase and Myxovirus [influenza
      virus] resistance induction) and its anti-VV effects in keratinocytes.
      CONCLUSIONS: Inhibition of S100A11 gene expression impairs the ability of
      keratinocytes to control VV replication via downregulation of IFN-lambda receptor
      IL-10R2.

PMID- 19577284
TI  - Indoor allergens in school and day care environments.
AB  - Most studies that have examined exposure to indoor allergens have focused on home
      environments. However, allergen exposures can be encountered in environments
      other than the home. For example, many children spend a large part of their time
      in schools and day care facilities. Over the past 2 decades, a large number of
      studies have been conducted in school and day care environments. However, the
      role of indoor exposures in allergy and asthma development or morbidity in these
      settings is not well characterized. The purpose of this review is to evaluate the
      importance of indoor allergen exposures in school and day care settings. We
      summarize the key findings from recent scientific literature, describe exposure
      characteristics, discuss the role of these exposures in relation to asthma and
      allergy symptoms, and provide information on the effectiveness of published
      interventions.

PMID- 19577287
TI  - Improved parthenogenetic development of vitrified-warmed bovine oocytes activated
      with 9% ethanol plus 6-DMAP.
AB  - The objective was to compare various activation protocols on developmental
      potential of vitrified bovine oocytes. Bovine oocytes matured in vitro for 23 h
      were vitrified with EDFSF30 in open pulled straws. After warming, they were
      cultured in vitro for 1h, followed by parthenogenetic activation. Vitrified
      warmed oocytes had a morphologically normal rate similar to that of controls
      (nonvitrified oocytes cultured in vitro for 24h; 98.6% vs. 100%, P>0.05). When
      vitrified-warmed oocytes were first activated with 7% ethanol for 5 min and then
      incubated in 6-dimethylaminopurin (6-DMAP) for 4h, cleavage and blastocyst rates
      were 41.2% and 23.2%, respectively, which were lower than those of controls
      (77.5% and 42.0%, P < 0.05). Subsequently, we varied the ethanol concentration to
      increase the effectiveness of parthenogenetic activation. When either 5%, 6%, 7%,
      8%, 9%, 10%, or 11% ethanol alone (for 5 min) or in combination with 6-DMAP (4h)
      was used to activate vitrified-warmed oocytes, cleavage rates ranged from 22.3%
      to 61.1% and blastocyst rates ranged from 1.1% to 30.6%. These rates were
      optimized when oocytes were treated with 9% ethanol plus 6-DMAP; this was
      verified in experiments evaluating other activation protocols with 9% ethanol,
      calcium ionophore A23187, or ionomycin alone, or in combination with DMAP or
      cycloheximide (CHX). In conclusion, the oocyte activation protocol affected
      developmental capacity of vitrified bovine oocytes; 9% ethanol (5 min) followed
      by 6-DMAP (4h) promoted optimal parthenogenetic activation.

PMID- 19577289
TI  - Call for global health-systems impact assessments.

PMID- 19577286
TI  - Defects along the T(H)17 differentiation pathway underlie genetically distinct
      forms of the hyper IgE syndrome.
AB  - BACKGROUND: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema,
      recurrent infections, skeletal and connective tissue abnormalities, elevated
      serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant
      and autosomal-recessive forms that manifest common and distinguishing clinical
      features. A majority of those with autosomal-dominant HIES have heterozygous
      mutations in signal transducer and activator of transcription (STAT)-3 and
      impaired T(H)17 differentiation. OBJECTIVE: To elucidate mechanisms underlying
      different forms of HIES. METHODS: A cohort of 25 Turkish children diagnosed with
      HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by
      IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with
      anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell
      differentiation was assessed by measuring the production of IL-17 and IFN-gamma,
      respectively. RESULTS: Six subjects had STAT3 mutations affecting the DNA
      binding, Src homology 2, and transactivation domains, including 3 novel ones.
      Mutation-positive but not mutation-negative subjects with HIES exhibited reduced
      phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1
      activation was unaffected. Both patient groups exhibited impaired T(H)17
      responses, but whereas STAT3 mutations abrogated early steps in T(H)17
      differentiation, the defects in patients with HIES with normal STAT3 affected
      more distal steps. CONCLUSION: In this cohort of Turkish children with HIES, a
      majority had normal STAT3, implicating other targets in disease pathogenesis.
      Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status,
      indicating that different genetic forms of HIES share a common functional
      outcome.

PMID- 19577288
TI  - Three-year randomized clinical trial to evaluate the clinical performance and
      wear of a nanocomposite versus a hybrid composite.
AB  - OBJECTIVES: Compare the 3-year clinical performance (wear as an additional
      parameter) of a nanocomposite and a microhybrid composite, versus ADA guidelines
      (2001) using direct (clinical/USPHS) and indirect (quantitative/3D laser scan and
      qualitative/SEM) methods, in parallel. MATERIALS AND METHODS: 18 Filtek Supreme
      and 17 Z100 restorations were placed in molars (split mouth model) and bonded
      with Single bond Adhesive. Restorations were evaluated at baseline and 6-, 12-,
      24-, 36-months of clinical service according to modified USPHS criteria. The
      gypsum replicas at each recall were used for 3D-Pro-laser scanning to quantify
      wear and the epoxy resin replicas were observed under SEM to study the
      qualitative wear patterns. Repaired restorations were considered functionally
      present and not failed. Restorations were judged as failed, whenever completely
      replaced or when scored Delta due to material related factors impairing clinical
      function. RESULTS: Filtek Supreme appeared better polishable than Z100 (p=0.0078;
      McNemar test). However, there were no significant differences between groups for
      other criteria including wear (p>0.05; Mann-Whitney U test). Qualitatively,
      fatigue wear at heavy occlusal contact areas (OCA), pitting at light OCA and
      scratches/striations along the food escape pathways were evident in almost all
      worn surfaces under SEM. CONCLUSIONS: At 3 years, nanocomposite and microhybrid
      composite meet ADA Acceptance Guidelines (2001) for tooth-colored restorative
      materials for posterior teeth.

PMID- 19577290
TI  - Generating substrate bound functional chemokine gradients in vitro.
AB  - Microcontact printing (mCP) is employed to generate discontinuous microscale
      gradients of active fractalkine, a chemokine expressed by endothelial cells near
      sites of inflammation where it is believed to form concentration gradients
      descending away from the inflamed area. In vivo, fractalkine is a transmembrane
      molecule extending its chemokine domain into the vascular lumen. Substrate bound
      in vitro gradients may thus closely resemble in vivo conditions. Direct mCP of
      sensitive proteins like fractalkine may cause partial protein denaturation and
      will not ensure correct orientation of the biologically active part of the
      molecules. Here, indirect mCP of a capture antibody recognizing a molecular tag
      on the target protein is successfully used to pattern tagged fractalkine in
      microscale gradient patterns. Fractalkine functions as an adhesion molecule for
      leukocytes. Cells expressing the fractalkine receptor are found to attach to the
      gradient structure at a density correlated with the fractional area covered by
      fractalkine. This indicates that the patterned fractalkine maintains its
      biological function. The method can be applied to in vitro studies of cell
      responses to the wide range of naturally surface-bound chemokines (haptotactic
      gradients). The use of a capture antibody facilitates control of the orientation
      of tagged molecules, thereby ensuring a high degree of bio-functionality through
      correct presentation and reduced protein denaturation.

PMID- 19577291
TI  - Proinflammatory and osteoclastogenic effects of beta-tricalciumphosphate and
      hydroxyapatite particles on human mononuclear cells in vitro.
AB  - Particulate wear debris can activate defence cells and osteoclasts at the bone
      implant interface possibly leading to bone resorption and implant failure.
      Cellular responses and inflammatory effects have been reported for particulate
      hydroxyapatite (HA). However, the immunological effects of particulate beta
      tricalciumphosphate (beta-TCP) have not been studied and the question of whether
      beta-TCP is more biocompatible in this regard as is HA remains to be determined.
      Therefore the present work investigates effects of endotoxin-free HA and beta-TCP
      particles of the same size (d(50)=1 microm) and dose (SAR 10:1) on human
      peripheral blood mononuclear cells in vitro. The production of proinflammatory
      cytokines (TNF-alpha, IL-1beta, IL-8) and cytokines connected to osteoclast and
      dendritic cell differentiation (OPG, RANKL, M-CSF, GM-CSF) was determined by
      ELISA. After 6 and 18 h of incubation HA and beta-TCP caused a quite similar
      induction of TNF-alpha, IL-1beta and IL-8. Effects of particles on the production
      of M-CSF and OPG were not detectable. However, in sharp contrast to HA, beta-TCP
      caused less induction of GM-CSF and not any of RANKL, both known for promoting
      dendritic cells and osteoclastogenesis respectively. Therefore these in vitro
      data suggest that wear debris of beta-TCP poses lesser risk of the detrimental
      effects of osteoclast induction known from HA.

PMID- 19577292
TI  - Osteogenic and adipogenic differentiation of rat bone marrow cells on non
      mulberry and mulberry silk gland fibroin 3D scaffolds.
AB  - This study investigates the potential of 3D silk scaffolds fabricated using
      tropical tasar non-mulberry, Antheraea mylitta and mulberry, Bombyx mori silk
      gland fibroin proteins as substrate for osteogenic and adipogenic differentiation
      of rat bone marrow cells (BMCs). The scaffolds are mechanically robust and show
      homogenous pore distribution with high porosity and interconnected pore walls.
      Low immunogenicity of fabricated silk scaffolds as estimated through TNF alpha
      release indicates its potential as future biopolymeric graft material. Rat bone
      marrow cells cultured on scaffolds for 28 days under static conditions in
      osteogenic and adipogenic media respectively led to induction of differentiation.
      Proliferation and spreading of fibroblasts and bone marrow cells on silk
      scaffolds were observed to be dependent on scaffold porosity as revealed through
      confocal microscopic observations. Histological analysis shows osteogenic
      differentiation within silk scaffolds resulting in extensive mineralization in
      the form of deposited nodules as observed through intense Alizarin Red S
      staining. Similarly, adipogenesis was marked by the presence of lipid droplets
      within scaffolds on staining with Oil Red O. Real-time PCR studies reveal higher
      transcript levels for osteopontin (Spp1), osteocalcin (Bglap2) and osteonectin
      (Sparc) genes under osteogenic conditions. Similarly, upregulated adipogenic gene
      expression was observed within A. mylitta and B. mori scaffolds under adipogenic
      conditions for Peroxisome proliferator activated receptor gamma (PPARgamma2),
      lipoprotein lipase (LPL) and adipocyte binding protein (aP2) genes. The results
      suggest suitability of silk fibroin protein 3D scaffolds as natural biopolymer
      for potential bone and adipose tissue engineering applications.

PMID- 19577293
TI  - Polyethylenimine coating to produce serum-resistant baculoviral vectors for in
      vivo gene delivery.
AB  - Recombinant baculoviral vectors efficiently transduce many types of mammalian
      cells. However, their in vivo applications are hampered by the sensitivity of the
      virus to complement-mediated inactivation. Based on our observation that the
      surface charge of baculovirus is negative at neutral pH, we developed a procedure
      to coat baculoviral vectors with positively charged polyethylenimine 25 kDa, a
      commonly tested non-viral gene delivery vector, through electrostatic
      interaction. This coating was effective in protecting baculoviral vectors against
      human and rat serum-mediated inactivation in vitro, providing transduction
      efficiencies comparable with that generated by the control virus used under a
      serum-free condition. Enhanced in vivo gene expression in the liver and spleen
      was observed after tail vein injection of the coated viruses into mice. When
      injected directly into human tumor xenografts in nude mice, the coated viruses
      suppressed tumor development more effectively than uncoated viral vectors. These
      findings demonstrated the usefulness of using a simple coating method to
      circumvent a major obstacle to in vivo application of baculoviral vectors. The
      method may also serve as a flexible platform technology for improved use of the
      vectors, for example introducing a targeting ligand and minimizing immune
      responses.

PMID- 19577294
TI  - Very early twin-to-twin transfusion syndrome and discordant activation of the
      renin-angiotensin system.
AB  - We present evidence of a first-trimester discordant renin-angiotensin system
      (RAS) response and structural abnormalities of the kidneys in twins with twin-to
      twin transfusion syndrome (TTTS). A dark red fetus and a pale fetus were
      spontaneously delivered at 13.5 weeks of gestation following a double intra
      uterine death. Pathological examination confirmed the placentation as
      monochorionic, with arteriovenous anastomoses on the chorionic plate. The donor
      twin had a normal heart and mildly hypoplastic kidneys, and the recipient twin
      had cardiomegaly and hypertrophic kidneys. Immunohistochemical analysis of the
      kidneys showed secretion of renin occurring in the donor but not in the recipient
      twin, more intense expression of angiotensin II receptor type 1 in the donor, and
      modifications of renal architectures in both twins. Renin protein appeared
      qualitatively higher in the placental territory of the recipient compared to that
      of donor. These findings indicate that hemodynamic discordance caused by vascular
      anastomoses may lead to serious physiologic and organic consequences as early as
      the first trimester. To our knowledge, this case presents the earliest first
      trimester TTTS confirmed by a complete anatomopathological examination and is the
      first TTTS case to show a first-trimester discordant RAS response confirmed by
      immunohistochemistry.

PMID- 19577295
TI  - Effectiveness of glyphosate and imazamox on the control of the invasive cordgrass
      Spartina densiflora.
AB  - The south-American cordgrass, Spartina densiflora, has become the dominant plant
      species on recent tidal marsh restorations in the Donana National Park (SW
      Spain). We examined the effect of different doses of glyphosate (720-7200 g a.i.
      ha(-1)) and imazamox (20-68 g a.i. ha(-1)) on growth and photosynthetic apparatus
      of S. densiflora. Imazamox had no effect on neither on growth nor photosynthetic
      apparatus of S. densiflora. On the contrary, glyphosate inhibited photochemical
      efficiency of photosynthesis from day one. Net photosynthetic rate, stomatal
      conductance and photosynthetic pigments and the number of new tillers were
      reduced. Glyphosate at high doses (ca. 7200 g a.i. ha(-1)) could be an
      appropriate method of control, since it has a negative effect over the
      photosynthetic apparatus and growth of S. densiflora. Furthermore, glyphosate and
      its main metabolite, AMPA, were not extracted from the soil, since they were
      retained by the very high iron and aluminum oxide content of this soil.

PMID- 19577296
TI  - Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by
      different dietary selenium status.
AB  - In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice
      exposed in drinking water to 50, 200 or 500microgAs/L for 24 months were
      investigated. All animals were fed low-selenium diet, however half of them were
      supplemented with sodium selenite in drinking water (200microgSe/L) to ensure the
      normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes
      and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18
      months in satellite groups showed considerable decrease in animals from non
      selenium supplemented groups in comparison to supplemented groups. A clear
      arsenic concentration-dependent increase in the number of malignant lymphoma
      associated with increase in the risk of death was observed (hazard ratio=0.91,
      1.46, and 2.24, for 50, 200 and 500microgAs/L, respectively). No significant
      influence of selenium dietary status on arsenic carcinogenicity was shown. A
      significant association between selenium supplementation status and increased
      risk of death of the animals from causes other than malignant tumors was found
      (HR=1.79, p=0.04).

PMID- 19577297
TI  - Effects of zinc exposure on the reproduction of Spodoptera litura Fabricius
      (Lepidoptera: Noctuidae).
AB  - Reproductive toxicity of Zn to insects was investigated in this study. By
      exposing phytophagous insect Spodoptera litura Fabricius to Zn in artificial
      diets of larvae, we investigated the effects of Zn on reproduction at ecological
      and molecular levels. A significantly shorter period of laying eggs was observed
      in S. litura exposed to 300-750mg Zn/kg. The oviposition rate, fecundity and
      hatchability of female adults treated with 750mg Zn/kg were significantly lower
      than those of the controls (31.43%, 20.95% and 52%, respectively, compared to the
      control). The Zn accumulation and vitellin (Vn) content in eggs were tested by
      inductively coupled plasma-atomic emission spectrometry and Bradford combining
      Western-blot, respectively. The results showed that Zn accumulated in the eggs,
      which has affected the weight and Vn content of eggs with significant negative
      correlations. The down-regulated expression levels of vitellogenin (Vg) mRNA were
      detected by real-time polymerase chain reaction (RT-PCR): the relative quantity
      of Vg mRNA was less than half of the controls at higher than 450mg Zn/kg wet
      weight. These results indicated that excess Zn made expression of Vg gene down
      regulated and caused poor accumulation of egg yolk, which led to a reduction in
      egg numbers and failure of eggs to hatch.

PMID- 19577298
TI  - Rethinking the systems of care definition: an indigenous perspective.
AB  - This paper will describe systems of care as a cultural phenomenon by highlighting
      western versus indigenous models of thinking. Inherent within the system of care
      definition are biases and assumptions that result in a highly linear and
      culturally bound process for understanding a "reality" that is not necessarily
      shared by all. Overarching concerns include value-laden language, the development
      of the systems of care principles, and the conceptualization of the changing
      definitions over time. Within the definition of systems of care presented, there
      are biases and embedded assumptions that continue to cause disparities in health
      for culturally diverse communities. The paper will examine these cultural biases
      and assumptions and their link to access, availability, and acceptability of
      services.

PMID- 19577299
TI  - Arterial spin-labeling MRI perfusion in tuberous sclerosis: correlation with PET.
AB  - Neuroimaging using magnetic resonance imaging (MRI) is required for the
      investigation of surgically intractable epilepsy. In addition to the standard MRI
      techniques, perfusion sequences can be added to improve visualization of the
      underlying pathological changes. Also, as arterial spin-labeling (ASL) MRI
      perfusion does not require contrast administration, it may even be advantageous
      in these patients. We report here on three patients with epilepsy and tuberous
      sclerosis who underwent brain MRI with ASL and positron emission tomography
      (PET), both of which were found to correlate with each other and with
      electrophysiological data.

PMID- 19577300
TI  - Assessment of nasal and paranasal sinus masses by diffusion-weighted MR imaging.
AB  - PURPOSE: To assess nasal and paranasal sinus masses by diffusion-weighted
      echoplanar magnetic resonance imaging (MRI). PATIENTS AND METHODS: This
      prospective study included 55 consecutive patients (34 males, 21 females; aged 14
      64 years, mean 39 years) with nasal and paranasal sinus masses. All underwent
      diffusion-weighted MRI using single-shot echoplanar imaging (EPI) with a b factor
      of 0.500 and 1000 s/mm2. Apparent diffusion coefficient (ADC) maps were
      constructed, allowing ADC values of the mass to be calculated and correlated with
      histopathological findings. RESULTS: The mean ADC value of nasal and paranasal
      sinus malignant lesions (1.10+/-0.25x10(-3) mm2/s) was significantly different
      (P=0.001) from that of benign lesions (1.78+/-0.41x10(-3) mm2/s). Also, there was
      a significant ADC difference between carcinoma and sarcoma (P=0.01) as well as
      between well differentiated and poorly differentiated malignancies (P=0.005).
      Using an ADC value of 1.53x10(-3) mm2/s as the threshold value for
      differentiating malignant from benign lesions, the best result obtained had an
      accuracy of 93%, sensitivity of 94%, specificity of 92%, a positive predictive
      value of 92% and negative predictive value of 94%. However, the use of 0.97x10(
      3) mm2/s and 1.16x10(-3) mm2/s as threshold values to differentiate carcinomas
      from sarcomas and poorly differentiated malignancy, respectively, gave the best
      results. CONCLUSION: The ADC value is a non-invasive imaging parameter that can
      be used to assess nasal and paranasal sinus masses, as it can help in the
      differentiation of malignant tumors from benign lesions, and in the
      characterization and grading of malignancies.

PMID- 19577301
TI  - Immunomodulation by duck defensin, Apl_AvBD2: in vitro dendritic cell
      immunoreceptor (DCIR) mRNA suppression, and B- and T-lymphocyte chemotaxis.
AB  - The present study analyzed the immunomodulatory potential of a newly identified
      duck beta-defensin, Apl_AvBD2. Recombinant Apl_AvBD2 expressed in HEK293T cells
      induced a concentration dependent in vitro migration of duck splenocytes, and
      spleen B- and T-lymphocytes, which was specifically inhibited by anti-Apl_AvBD2
      polyclonal antibodies. Among the transcripts of 13 immunologically important
      genes analyzed in cultured splenocytes for the early immunomodulatory effect of
      Apl_AvBD2, dendritic cell immunoreceptor (DCIR) mRNA was found to be
      significantly down-regulated. However, there were no major changes in the
      expression levels of transcripts for cell surface proteins (MHC I, MHC II 2 beta
      chain, TCR-beta, TLR-7, DCAR, CD44, and CD58) and cytokines (IL-2, IFN-gamma,
      RANTES, MIP-1beta-like and MCP-1 like chemokines). Our results reveal chemotactic
      and immunomodulatory properties of Apl_AvBD2, two important functions that would
      help in employing this protein as a molecular adjuvant with avian vaccines.

PMID- 19577302
TI  - A transferrin-like homolog in amphioxus Branchiostoma belcheri: Identification,
      expression and functional characterization.
AB  - Previous studies have shown the universal presence of transferrin (Tf) in both
      invertebrates and vertebrates, but little information is available regarding Tf
      in amphioxus, a protochordate on the evolutionary boundary between invertebrates
      and vertebrates. Here we isolated a Tf-like homolog from Branchiostoma belcheri,
      which encodes a deduced protein, BbTfl, of 1256 amino acids containing a N
      terminal signal peptide, a conserved transferrin domain in its N-terminal lobe,
      with a putative iron-binding site consisting of Asp63 and Try188 and another
      transferrin domain in its C-terminal lobe with an long intervening sequence of
      305 amino acids. Phylogenetic analysis shows BbTfl is grouped together with all
      the invertebrate Tfs and located at the base of melanotransferrins and other Tfs.
      Quantitative PCR analysis reveals that exposure to Escherichia coli and Vibrio
      anguillarum causes a significant increase in BbTfl expression mainly in the gut
      within 12-24h, suggesting that BbTfl is a positive acute phase reactant involved
      in the immune defense of B. belcheri. The recombinant N-terminal lobe, BbTflN, is
      able to bind iron and to inhibit E. coli and Staphylococcus aureus growth.
      Moreover, the antibacterial activity of BbTflN markedly decreases in the presence
      of excess iron. All these results provide a direct empirical evidence
      establishing a definitive link between binding to iron and bacterial growth
      inhibiting activity. It is also shown that BbTfl is expressed in a tissue
      specific manner, with the most abundant expression in the hepatic caecum, hind
      gut and ovary, supporting the idea that the digestive system including the
      hepatic caecum of amphioxus is the primary tissue involved in acute phase
      response.

PMID- 19577303
TI  - Molecular characterization of novel interferon gamma receptor 1 isoforms in
      zebrafish (Danio rerio) and goldfish (Carassius auratus L.).
AB  - Interferon gamma (IFNgamma) is a highly pleotropic pro-inflammatory and anti
      viral cytokine that mediates its effects by binding to a receptor complex
      composed of interferon gamma receptors 1 and 2 (IFNGR1 and IFNGR2). Using gene
      synteny analysis, we identified a distinct isoform of the zebrafish IFNGR1. The
      two zebrafish IFNGR1 called here IFNGR1-1 and IFNGR1-2 were used to identify the
      respective cDNA sequences of the goldfish IFNGR1-1 and IFNGR1-2. Analysis of
      protein sequences revealed that all fish IFNGR1 species have potential JAK1 and
      STAT1 docking sites. Phylogenetically, teleost IFNGR1 proteins grouped separately
      from those of higher vertebrates. Q-PCR analysis revealed that while the
      constitutive mRNA levels of the two zebrafish IFNGR1 isoforms were comparable in
      different tissues examined, the goldfish IFNGR1-1 tissue expression was
      substantially higher than that of IFNGR1-2. Q-PCR analysis of goldfish immune
      cell populations revealed highest expression of both receptor isoforms in
      monocytes. Incubation of goldfish macrophages with recombinant goldfish IFNgamma2
      (rgIFNgamma2) up-regulated expression of both IFNGR1-1 and IFNGR1-2, while
      treatment of cells with rgTNFalpha2 only increased the expression of IFNGR1-1.
      Treatment with rgTGFbeta resulted in more modest increases in expression of both
      receptor isoforms only after prolonged treatment. In vitro binding studies
      indicated that rgIFNGR1-1 bound to rgIFNgamma1 but not rgIFNgamma2, while the
      rgIFNGR1-2 bound to rgIFNgamma2. Thus, unlike mammals that have a single IFNGR1,
      cyprinid fish have two distinct IFNGR1 isoforms that preferentially bind
      corresponding ligands, IFNgamma1 and IFNgamma2, respectively, suggesting that the
      type II interferon system of these fish species is distinct from that of higher
      vertebrates.

PMID- 19577304
TI  - Multimeric and trimeric subunit SP-D are interconvertible structures with
      distinct ligand interaction.
AB  - Surfactant protein-D (SP-D) is a calcium dependent lectin in the innate immune
      system that facilitates clearance of microbes. The protein is associated with
      mucosal surfaces, and also found in bronchoalveolar lavage, serum and amniotic
      fluid. Human SP-D includes trimeric subunits and multimeric assemblies of
      trimeric subunits, which are stabilized by N-terminal interchain disulfide
      crosslinks. An N-terminal structural polymorphism (Met11Thr) and associated O
      glycosylation are previously shown accompanied by incomplete multimerization and
      with a relative low proportion of multimeric Thr11 SP-D compared to Met11 SP-D.
      Multimerization has proven important for enhancement of microbial phagocytosis.
      In the present study defined multimeric forms of Met11Thr SP-D were isolated from
      human amniotic fluid. Implementation of ManNAc-affinity chromatography allowed
      high recovery of natural trimeric SP-D subunits. However, affinity chromatography
      increased the relative proportion of multimers at the expense of natural trimeric
      subunits. Multimeric SP-D partially disassembled to form trimeric subunits. The
      resulting distribution of structural forms was independent of the Met11Thr
      genotype. Trimeric and multimeric SP-D appeared with distinct patterns of
      disulphide crosslinking, which partly changed according to interconversion
      between the structural forms. Solid phase assays demonstrated that trimeric SP-D
      subunits showed greater binding to LPS and PGN, but lower binding to mannan and
      LTA, than SP-D multimers. Trimeric SP-D subunits also showed greater binding to
      endogenous lipoproteins: LDL, oxLDL, and HDL, than multimeric SP-D. In
      conclusion, purified trimeric and multimeric SP-D represent separate and only
      partly interconvertible molecular populations with distinct biochemical
      properties.

PMID- 19577305
TI  - Retinal artery occlusion: associated systemic and ophthalmic abnormalities.
AB  - OBJECTIVE: To investigate systematically the various associated systemic and
      ophthalmic abnormalities in different types of retinal artery occlusion (RAO).
      DESIGN: Cohort study. PARTICIPANTS: We included 439 consecutive untreated
      patients (499 eyes) with RAO first seen in our clinic from 1973 to 2000. METHODS:
      At first visit, all patients underwent detailed ophthalmic and medical history,
      and comprehensive ophthalmic evaluation. Visual evaluation was done by recording
      visual acuity, using the Snellen visual acuity chart, and visual fields with a
      Goldmann perimeter. Initially they also had carotid Doppler/angiography and
      echocardiography. The same ophthalmic evaluation was performed at each follow-up
      visit. MAIN OUTCOME MEASURES: Demographic features, associated systemic and
      ophthalmic abnormalities, and sources of emboli in various types of RAO. RESULTS:
      We classified RAO into central (CRAO) and branch (BRAO) artery occlusion. In both
      nonarteritic (NA) CRAO and BRAO, the prevalence of diabetes mellitus, arterial
      hypertension, ischemic heart disease, and cerebrovascular accidents were
      significantly higher compared with the prevalence of these conditions in the
      matched US population (all P<0.0001). Smoking prevalence, compared with the US
      population, was significantly higher for males (P = 0.001) with NA-CRAO and for
      women with BRAO (P = 0.02). Ipsilateral internal carotid artery had > or =50%
      stenosis in 31% of NA-CRAO patients and 30% of BRAO, and plaques in 71% of NA
      CRAO and 66% of BRAO. An abnormal echocardiogram with an embolic source was seen
      in 52% of NA-CRAO and 42% of BRAO. Neovascular glaucoma developed in only 2.5% of
      NA-CRAO eyes. CONCLUSIONS: This study showed that, in CRAO as well as BRAO, the
      prevalence of various cardiovascular diseases and smoking was significantly
      higher compared with the prevalence of these conditions in the matched US
      population. Embolism is the most common cause of CRAO and BRAO; plaque in the
      carotid artery is usually the source of embolism and less commonly the aortic
      and/or mitral valve. The presence of plaques in the carotid artery is generally
      of much greater importance than the degree of stenosis in the artery. Contrary to
      the prevalent misconception, we found no cause-and-effect relationship between
      CRAO and neovascular glaucoma.

PMID- 19577306
TI  - Bacillus cereus as a biotemplating agent for the synthesis of zinc oxide with
      raspberry- and plate-like structures.
AB  - Currently the development of green chemistry approach with the use of biomaterial
      based activities of microbial cells in the synthesis of various nanostructures
      has attracted a great attention. In this study, we report on the use of
      bacterium, Bacillus cereus as a biotemplating agent for the formation of zinc
      oxide nanoparticles with raspberry- and plate-like structures through a simple
      thermal decomposition of zinc acetate by maintaining the original pH of the
      reaction mixtures. Possible mechanism on the formation of the nanostructures is
      proposed based on the surface chemistry and biochemistry processes involved
      organic-inorganic interactions between zinc oxide and the microbial cells.

PMID- 19577307
TI  - Who is MADD? Mixed anxiety depressive disorder in the general population.
AB  - BACKGROUND: Diagnostic criteria for (subthreshold) mixed anxiety depression
      (MADD) were proposed in DSM-IV. Yet the usefulness of this classification is
      questioned. We therefore assessed the prevalence of MADD, and investigated
      whether MADD adds to separate classifications of pure subthreshold depression and
      anxiety. METHOD: Data of the Netherlands Mental Health and Incidence Study were
      used. RESULTS: The 12-month prevalence of MADD was 0.6%. Between the three
      subthreshold categories few differences were found with regard to socio
      demographic variables, care utilisation and functioning. Course in MADD seems
      more favourable and MADD is not a stable diagnosis over time. LIMITATIONS: The
      MADD criteria used in the present study differed slightly from the proposed
      criteria in DSM-IV and sample sizes were small. CONCLUSIONS: Given these results,
      MADD is not a relevant diagnosis in terms of prevalence and consequences when
      classified according to the currently proposed criteria.

PMID- 19577309
TI  - Re-evaluation of the role of STOX1 transcription factor in placental development
      and preeclampsia.
AB  - Preeclampsia is a common disease of pregnancy, characterized by high blood
      pressure and proteinuria appearing from the second trimester of gestation.
      Preeclampsia has been shown to have a strong genetic component. In 2005 a
      positional cloning project led to the discovery of the STOX1 transcription
      factor, and mutations of this gene were proposed as causal for preeclampsia in
      Dutch families. Despite the publication of three contradictory studies, we have
      shown by analyzing the functional effects of STOX1 that its overexpression in
      choriocarcinoma cells recapitulates several transcriptomic aspects of
      preeclampsia. In this review, the current literature is analyzed to evaluate the
      possible involvement of STOX1 in the pathogenesis of this disease. While
      preeclampsia obviously cannot be considered as a disease caused by mutation in a
      single gene, we argue that STOX1 may be at the center of common pathways leading
      to preeclampsia.

PMID- 19577308
TI  - Dimensional predictors of response to SRI pharmacotherapy in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is clinically heterogeneous.
      Previous studies have reported different patterns of treatment response to
      serotonin reuptake inhibitors (SRI) based on symptom dimension. Our objective was
      to replicate these results in OCD patients who participated in one of four
      randomized, placebo-controlled, clinical trials (RCT). METHODS: A total of 165
      adult OCD subjects participated in one or more eight-week RCT with clomipramine,
      fluvoxamine, or fluoxetine. All subjects were classified as having major or minor
      symptoms in four specific OC symptom dimensions that were derived in a previous
      factor analytic study involving many of these same patients. Ordinal logistic
      regression was used to test the association between OC symptom dimensions and SRI
      response. RESULTS: We found a significant association between the symptom
      dimension involving sexual, religious and harm-related obsessions as well as
      checking compulsions (AGG/SR) and improved SRI response. This increased rate of
      SRI response was experienced primarily by individuals with harm-related
      obsessions. Over 60% of patients with AGG/SR OCD symptoms were rated as very much
      improved after SRI treatment. LIMITATIONS: As some of the RCTs included were
      conducted prior to the development of the Yale-Brown Obsessive-Compulsive Scale
      (Y-BOCS), improvement in OCD severity was assessed using the Clinical Global
      Improvement (CGI) Scale. Data from the double-blind and open-label continuation
      phases of these trials was collapsed together to increase statistical power.
      CONCLUSIONS: Patients with OCD vary in their response to SRIs. The presence of
      AGG/SR symptoms is associated with an initial positive response to SRIs. These
      data add to the growing body of work linking central serotonin systems with
      aggressive behavior.

PMID- 19577310
TI  - MHC haplotypes and response to immunocontraceptive vaccines in the brushtail
      possum.
AB  - The possum is a major invasive pest in New Zealand. One option for its control is
      the use of immunocontraceptive vaccines. Initial trials of vaccines have shown
      individual variation in response. The use of vaccines on wild populations could
      result in the evolution of a resistant population through selection for possums
      that remain fertile because of low or no response. Understanding the basis of
      this variation is therefore important. The major histocompatibility complex (MHC)
      is an important influence on the nature of immune responses. This study has
      investigated the relationship between MHC alleles and individual immune responses
      to immunocontraceptive vaccines comprising zona pellucida peptides. We identified
      MHC alleles and putative haplotypes, and compared these between individuals with
      measured responses to immunocontraceptive vaccines. Two haplotypes were found to
      associate significantly with differences in vaccine response. Possums that
      carried haplotype 6 showed reduced responsiveness to one vaccine, while possums
      that carried haplotype 9 showed increased responsiveness to a separate vaccine.
      The identification of MHC haplotypes associated with different responses to
      immunocontraceptive vaccines offers the opportunity to understand what factors
      trigger non-response and the persistence of fertility in some individuals, and
      may allow vaccines to be optimised to minimise non-responsiveness.

PMID- 19577311
TI  - Effects of exposure to acetochlor on the expression of thyroid hormone related
      genes in larval and adult rare minnow (Gobiocypris rarus).
AB  - Acetochlor is a commonly used herbicide in agricultural environments, which can
      accelerate T(3)-induced metamorphosis in amphibians. However, effects of
      acetochlor on the thyroid system in fish are still unclear at environmentally
      relevant concentrations. In this study, expression profiles of thyroid hormone
      receptor alpha (tralpha), deiodinase (d1 and d2), malic enzyme (me), and sodium
      iodide symporter (nis) genes were determined in larval and adult rare minnow
      (Gobiocypris rarus) after exposure to different levels of acetochlor (20, 200,
      and 2000ng/l) for 21 days, respectively. Furthermore, plasma thyroid hormones
      (THs) levels in adults were evaluated simultaneously. The results showed that d1,
      d2, me, and nis mRNA levels were significantly down-regulated in the larvae.
      Similar expression changes of these genes in female brains were found. However,
      in adult livers, these gene expressions had no significantly effects, except the
      tralpha mRNA level significantly up-regulated. These results indicated that
      exposure to acetochlor could result in tissue-specific alternative expression of
      TH-related genes in adults. Moreover, the expression of d2 and me showed a
      positive correlation with plasma T(4) levels in female brains. Therefore, larval
      development and adult brain of rare minnow could be affected by acetochlor at
      environmentally relevant concentrations.

PMID- 19577312
TI  - Inhibition of thyroidal status related to depression of testicular development in
      Sebastiscus marmoratus exposed to tributyltin.
AB  - Organotin compounds, such as tributyltin (TBT), which have been used as
      antifouling biocides, are still of concern with regard to their effects on marine
      organisms, and especially their reproductive systems. We investigated the
      toxicity of TBT at environmentally relevant concentrations (1, 10, and 100 ng/L)
      on testicular development in a marine fish, Sebastiscus marmoratus. After
      exposure for 50 days, the gonadosomatic index had decreased in a dose-dependent
      manner, and there was a reduced number of mature sperm and an abundance of the
      late stages of spermatocysts in the testes of S. marmoratus. Exposure has also
      caused serious histological damage to the testes including interstitial fibrosis
      and pyknotic nuclei. Analysis of the thyroid status revealed severe damage to the
      thyroid gland, decreased triiodothyronine and thyroxine in the serum and low
      expression of thyroid hormone receptor alpha in the testes at this time. Pearson
      correlation analysis indicated that the levels of thyroxine in the serum were
      significantly correlated with the gonadosomatic index. These results suggest that
      inhibition of thyroidal status induced by TBT might be one of the mechanisms
      affecting testicular development.

PMID- 19577314
TI  - A rare familiar case of hereditary bisalbuminemia and diabetic predisposition: a
      possible predictive link?
AB  - We present a case report of hereditary bisalbuminemia in an Italian family with
      three affected members. Bisalbuminemia represents a genetic variant of the
      albumin, it will then be permanent, or acquired and then be transient. It is
      characterized by the presence of two albumin bands in electrophoresis: the first
      band with the same mobility of the normal albumin, the second band with a fast
      variable or a slow variable. The double band of albumin was detected fortuitously
      on a routine analytical study of an adult woman who was referred to our
      laboratory with an increase of fasting glucose value, this originated the study
      of the rest of the members of the family. Finally, it is like the genetic
      peculiarity of this family core show a possible predictive link between
      bisalbuminemia on one hand and the predisposition to type II diabetes mellitus on
      the other hand. As a result of such high probability we are eager to continue
      further search at our medicine predictive centre.

PMID- 19577315
TI  - Bone marrow cell therapy prevents infarct expansion and improves border zone
      remodeling after coronary occlusion in rats.
AB  - BACKGROUND: Since the cell therapy benefits for myocardial infarction are mainly
      related to infarct reduction by regenerating lost myocardium or increasing
      survival of tissues at risk, we evaluated the effects of bone marrow-derived
      mononuclear cells (MNC), implanted after the completion of necrosis, on infarct
      progression and cardiac remodeling. METHODS: After 48 h of induction of
      myocardial infarction (MI), Lewis-inbred rats were injected with 6 * 10(6) cells
      (MI+MNC) or saline (MI). After six weeks, scar dimension, ventricular morphology
      and function were analyzed by echocardiography followed by histomorphology of the
      infarcted and border zones. RESULTS: After therapy, the relative size of the
      infarct was smaller in MI+MNC (37 +/- 1% of the left ventricle) than in MI (43 +/
      1%). While the MI group exhibited parallel elongation of the infarcted (31.6 +/-
      3.8% increase) and reminiscent ventricular portions (33.5 +/- 3.7%), MNC therapy
      preserved the initial infarct length. Infarcted walls were thicker (979 +/- 31
      mm) in the MNC group than in the untreated group (709 +/- 41 mm), also
      demonstrating an absence of infarct expansion. In the border zones, MNC led to
      increased capillary densities and capillary/myocyte ratios. The cardiac systolic
      function remained depressed in MI, but improved by 19 +/- 5% in MI+MNC which
      reduced the incidence of pulmonary arterial hypertension (37.5% in MI and 6.25%
      in MI+MNC). CONCLUSION: MNC therapy prevented the infarct expansion and thinning
      related to cardiac remodeling and was associated with an improvement of border
      zone microcirculation: as a result, MNC therapy reduced typical MI dysfunctional
      repercussions.

PMID- 19577313
TI  - Multicomponent exercise program improves blood lipid profile and antioxidant
      capacity in older women.
AB  - This study intended to determine the effect of multicomponent exercise on blood
      lipid profile and on antioxidant capacity in older women. Forty women aged 60-80
      years participated in a supervised multicomponent exercise program. Plasma
      contents of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C)
      and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG),
      apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B-100), total antioxidant
      status (TAS) and the enzymatic activities of glutathione reductase (GR) and
      glutathione peroxidase (GPx) were evaluated before and after 8-month training.
      The multicomponent exercise program induced a significant decrease in TG, TC/HDL
      C and Apo B/Apo A-1 and a significant increase in HDL-C and Apo A-1 (p<0.05).
      There was a significant increase in plasma TAS as well as GR and GPx enzyme
      activities. The present data show that an 8-month supervised moderate-intensity
      multicomponent exercise program resulted in beneficial improvements of blood
      lipid profile that were accompanied by positive modulation of antioxidant
      capacity.

PMID- 19577316
TI  - Factors associated with gastrointestinal parasite infection in dogs in Rio de
      Janeiro, Brazil.
AB  - Factors associated with parasitism by helminths and protozoans in 500 dogs
      presented to three veterinary clinics in the municipality of Rio de Janeiro from
      November 2003 to September 2004 were evaluated. Dogs were submitted to physical
      examination and owners were interviewed about the animal's management. One fecal
      sample from each dog was examined by centrifugal flotation and sedimentation
      methods followed by the safranin-methylene blue staining technique. Positive
      results for gastrointestinal parasites were detected in 46.4% of the examined
      samples. Infection with protozoans (29.6%) was more frequent than with helminths
      (23.2%). Cryptosporidium sp. (26.2%) and Ancylostoma sp. (15.2%) were the most
      frequent parasites. Logistic regression analysis showed that age (p<0.001),
      access to soil (p<0.001), hygiene of the environment (p=0.001), illness
      (p=0.007), owner's level of education (p<0.006) and veterinary clinic (p=0.043)
      were associated with gastrointestinal parasite infections in dogs. Treatment and
      control are especially important for puppies. Adult dogs should be submitted to
      fecal examination before treatment, placing special emphasis on those that
      present one or more factors associated with infection.

PMID- 19577317
TI  - Evaluating different PrP genotype selection strategies for expected severity of
      scrapie outbreaks and genetic progress in performance in commercial sheep.
AB  - Stochastic computer simulations were used for quantifying the effect of selecting
      on prion protein (PrP) genotype on the risk of major outbreaks of classical
      scrapie and the rate of genetic progress in performance in commercial sheep
      populations already undergoing selection on performance. The risk of a major
      outbreak on a flock was measured by the basic reproduction ratio (R(0)). The
      effectiveness of different PrP selection strategies for reducing the population
      risk was assessed by the percentage of flocks with R(0)<1. When compared with the
      scenario where there was no selection on PrP genotype, selection against the VRQ
      allele had a minimal impact on genetic progress for performance traits. However,
      this strategy was not sufficient to eliminate the population risk after 15 years
      of selection when the initial frequency of the ARR allele was relatively low.
      More extreme PrP selection strategies aimed at increasing the frequency of the
      ARR allele and decreasing the frequency of the VRQ allele led to decreases in the
      rate of genetic progress for performance but reduced the population risk to very
      low values. The reduction in genetic progress was only large when the initial ARR
      frequency was low and, in general, the risk of major epidemics was very small
      when the frequency of this allele reached 0.7.

PMID- 19577318
TI  - Lower frequency of the 5/5 homozygous CNDP1 genotype in South Asian Surinamese.
AB  - We investigated the frequency of the 5/5 homozygous CNDP1 (carnosinase) genotype,
      which was found to be associated with a reduced risk of developing diabetic
      nephropathy, in three ethnic groups in The Netherlands. Particularly interesting
      were the South Asian Surinamese, who have a high prevalence of diabetic
      nephropathy. Furthermore, we investigated the association between this gene and
      carnosinase activity in South Asian Surinamese and whether carnosinase was
      expressed in the kidney. We genotyped 290 South Asian Surinamese, 532 African
      Surinamese, and 472 White Dutch in a cross-sectional population study.
      Furthermore, an independent cohort of South Asian Surinamese was genotyped. In
      this population, carnosinase activity was measured in serum. Immunostaining and
      in situ hybridization for CNDP1 were performed on kidney tissue. Both South Asian
      populations had lower frequencies of the 5/5 homozygous genotype than African
      Surinamese and White Dutch (23.0%, 27.2%, 38.2%, and 41.3%, respectively; chi
      square, p<0.001). This genotype showed a lower carnosinase activity in South
      Asian Surinamese (Wilcoxon rank-sum, p=0.03). CNDP1 was expressed in the kidney.
      South Asian Surinamese have a lower frequency of the 5/5 homozygous genotype,
      which was associated with lower carnosinase activity. Our study provides an
      indication that South Asian Surinamese are genetically at risk for developing
      diabetic nephropathy.

PMID- 19577319
TI  - Are transposable elements simply silenced or are they under house arrest?
AB  - Despite their role as key players in evolution, it is commonly thought that
      transposable elements are selected against and silenced. However, their
      importance in chromosomal biology and, therefore, cell division suggests that
      their presence in many eukaryote genomes is the result of their having been
      selected as major components of heterochromatin.

PMID- 19577321
TI  - Managed relocation: a nuanced evaluation is needed.

PMID- 19577322
TI  - Cultural evolution and the human predicament.
AB  - For decades, scientists have been calling for action to halt environmental
      degradation, and there has been a substantial (but variable) response from the
      ecological and evolutionary research communities. Nonetheless, the degradation
      continues more rapidly than ever, by almost any biophysical measure. Here I
      briefly summarize and frame the situation, and suggest some major research
      thrusts for our community to accelerate the needed cultural responses, given that
      accumulating human impacts could threaten the collapse of global civilization.

PMID- 19577320
TI  - Clinical characteristics of pleomorphic carcinoma of the lung.
AB  - BACKGROUND: Pleomorphic carcinoma of the lung is a malignant epithelial tumor
      that contains carcinomatous and sarcomatoid components. Due to its rarity, few
      studies have been reported, and its clinical and pathological characteristics
      remain unclear. METHOD: We retrospectively investigated 22 cases of pleomorphic
      carcinoma of the lung. RESULTS: Fifteen cases were diagnosed by surgical
      resection, 4 by autopsy, and 3 by transbronchial biopsy. Nineteen patients were
      male and 3 were female, and their mean age at diagnosis was 68.3 years (+/-10.1).
      Eighteen were current- or ex-smokers with substantial smoking histories (mean
      46.4 pack-years). Sixteen patients had symptoms: hemoptysis and cough were
      commonly seen. Chest computed tomography (CT) findings revealed that the tumors
      were quite large (mean diameter 45.3+/-21.9mm; range 14-110mm), and 21 tumors
      were peripherally located. Positron emission tomography with 18-fluorodeoxy
      glucose (FDG-PET) was performed in 12 patients, and the Standardized Uptake Value
      (SUV) tended to be high (9.44+/-4.98). In the 15 patients who underwent surgical
      resection, recurrence was common; systemic metastases were also frequently found.
      Patients who had received surgical treatment with proper follow-up care survived
      longer than those who did not undergo surgery. Responses to chemotherapy were
      generally poor, although 1 patient exhibited partial response to gefitinib.
      CONCLUSIONS: Pulmonary pleomorphic carcinoma has strong malignant potential with
      frequent distant metastases, as has already been reported. However, this study
      demonstrated that surgical treatment and appropriate follow-up therapy might
      result in better prognoses.

PMID- 19577323
TI  - Assisted colonization is a techno-fix.

PMID- 19577324
TI  - Understanding the role of monocytic cells in liver inflammation using parasite
      infection as a model.
AB  - Uncontrolled inflammation is a major cause of pathogenicity during chronic
      parasite infections. Novel therapies should therefore aim at re-establishing the
      balance between pro- and anti-inflammatory signals during disease to avoid tissue
      damage and ensure survival of the host. In this context, we are intending to
      identify strategies capable of inducing counter-inflammatory activity in injured
      liver and thereby increasing the resistance of the host to African
      trypanosomiasis as a model for parasite infection. Here, recent evidence is
      summarized revealing how monocytic cells recruited to the liver of African
      trypanosome-infected mice develop an M1 or M2 activation status, thereby
      maintaining the capacity of the host to control parasite growth while avoiding
      the development of liver damage, which otherwise culminates in early death of the
      host.

PMID- 19577326
TI  - Long-term safety of repeated administrations of a new formulation of botulinum
      toxin type A in the treatment of glabellar lines: interim analysis from an open
      label extension study.
AB  - BACKGROUND: A new formulation of botulinum toxin type A (BoNT-A) (Dysport) has
      recently been approved in the United States for the treatment of glabellar lines.
      OBJECTIVE: We sought to evaluate the long-term safety of repeated administrations
      of this BoNT-A formulation. METHODS: In all, 768 individuals (1500 planned) from
      phase III clinical trials received as many as 6 repeated treatments of open-label
      BoNT-A (50 U) over 17 months, with a minimum of 85 days between treatments.
      Participants received a telephone call at day 7 postinjection to check for
      adverse event (AE), with clinical evaluations on days 14 and 30, and monthly
      until retreatment, study completion, or early termination. Safety end points were
      AEs, changes in vital signs, and assessment of serum-neutralizing antibodies to
      BoNT-A. RESULTS: Of the 285 participants reporting at least one treatment
      emergent AE at the interim analysis cutoff, only 74 (26%) reported at least one
      possibly or probably related event after 2259 treatments with BoNT-A. The
      incidence of treatment-emergent AEs around the injection sites and eyes was low
      (< or = 3%). Ten participants (1%) experienced 10 instances of ptosis. No
      participants developed neutralizing antibodies to BoNT-A or clinically
      significant changes in vital signs. LIMITATIONS: This is an interim analysis of a
      larger multicenter extension study. CONCLUSIONS: Multiple treatments with BoNT-A
      (50 U) over 17 months were well tolerated.

PMID- 19577325
TI  - Sub-cellular distribution of glutathione in an Arabidopsis mutant (vtc1)
      deficient in ascorbate.
AB  - Glutathione and ascorbate are considered the major redox buffers in plant cells.
      They are implicated in many reactions at the sub-cellular level. However,
      information about the location and quantification of glutathione in the different
      sub-cellular compartments is very scarce and it has been obtained mainly using
      organelle purification and chemical quantification. We have used a glutathione
      antibody to immunolabel and quantify the total glutathione in leaves from wild
      type Arabidopsis thaliana (Col-0) and an A. thaliana mutant (vtc1) deficient in
      ascorbate. Spectrophotometrical quantification has shown that this mutant has a
      higher content of glutathione during plant development compared with Col-0 [Pavet
      V, Olmos E, Kiddle G, Mowla S, Kumar S, Antoniw J, et al. Ascorbic acid
      deficiency activates cell death and disease resistance responses in Arabidopsis.
      Plant Physiology 2005;139:1291-03]. We have observed, using immunolabelling
      techniques, that mitochondria showed the highest density of glutathione labelling
      in both Col-0 and vtc1 plants during all developmental stages and that the lowest
      density occurred in the chloroplasts, for both lines. However, the distribution
      of glutathione in the different sub-cellular compartments indicates that the
      chloroplasts contain about 62-75% of the total cellular glutathione and that the
      mitochondria represent the second greatest pool, with about 15-25% of the total
      cellular glutathione. It has been observed previously that the vtc1 mutant
      exhibits an induction of cell death and disease resistance in the face of
      pathogen attack. The differing distributions and concentrations of glutathione in
      the mitochondria of wild-type A. thaliana and the vtc1 mutant is discussed.

PMID- 19577327
TI  - Neutrophilic dermatosis complicating lenalidomide therapy.
AB  - Lenalidomide, a derivative of thalidomide, is an immunomodulatory agent
      introduced in 2004 for the treatment of multiple myeloma in combination with
      dexamethasone. It is also indicated for the treatment of myelodysplastic syndrome
      and is currently under investigative use for metastatic melanoma. We present a
      case of neutrophilic dermatosis involving predominantly the lower extremities in
      a patient receiving lenalidomide therapy for multiple myeloma.

PMID- 19577328
TI  - Alopecia secondary to mesotherapy.
AB  - Mesotherapy has recently become an advertised method for the treatment of
      different types of alopecia despite the lack of any data regarding its efficacy
      and possible side effects. The substances injected into the scalp include
      "cocktails" of natural plant extracts, homoeopathic agents, vitamins,
      vasodilators, and drugs that may stimulate hair growth, such as finasteride and
      minoxidil. We report two cases of patchy alopecia that developed after
      mesotherapy for the treatment of androgenetic alopecia. In the first patient,
      alopecia developed after injections of the heparinoid vasodilator mesoglycan; the
      3-month follow-up examination revealed a small residual area of cicatricial
      alopecia. The second patient developed reversible alopecia after multiple scalp
      injections of homeopathic agents. These cases underline the possible risks of
      mesotherapy as a therapeutic technique for hair loss.

PMID- 19577329
TI  - Scalp necrosis in giant cell arteritis: case report and review of the relevance
      of this cutaneous sign of large-vessel vasculitis.
AB  - Giant cell arteritis (GCA) is a systemic vasculitis associated with severe
      complications such as loss of vision and, rarely, scalp necrosis. We present a
      patient with GCA who had bilateral scalp necrosis and an erythrocyte
      sedimentation rate of only 21 mm after the first hour. Therapy with systemic
      steroids, which were slowly tapered over 1 year, led to secondary wound healing
      without recurrence. As there are no systematic reviews on the occurrence of scalp
      necrosis in patients with GCA, we performed a literature research and meta
      analysis and discovered 78 cases published between 1946 and 2007. Analysis of the
      data revealed that GCA with scalp necrosis is associated with a higher incidence
      of vision loss (32%) and other visual defects (37.3%) than GCA without scalp
      necrosis (visual disturbances in up to 20%). GCA with scalp necrosis is also
      associated with an increased mortality (standard mortality ratio [SMR], 4.2) in
      contrast to GCA without scalp necrosis, which has no significantly higher
      mortality than age-matched controls (SMR 0.8-1.034). In patients with scalp
      necrosis, the diagnosis of GCA was made about 1 month later than in patients
      without scalp necrosis, and scalp necrosis was never reported to occur after
      onset of therapy with glucocorticoids. Thus, for reasons beyond potential loss of
      vision, physicians should be alert for symptoms of GCA as only timely diagnosis
      and immediate therapy may prevent serious complications and increased mortality.

PMID- 19577330
TI  - Clinical, histopathologic, and immunophenotypic features of lymphomatoid
      papulosis with CD8 predominance in 14 pediatric patients.
AB  - BACKGROUND: Lymphomatoid papulosis (LyP) is a cyclic papulonodular eruption that
      is clinically benign and histologically malignant. Association with hematologic
      neoplasias has been reported in 5% to 20% of all cases. OBJECTIVE: We sought to
      review the clinical and histopathologic features of LyP in pediatric patients.
      METHODS: We searched for the records of all patients with a clinical and
      histopathologic diagnosis of LyP seen at our clinic from January 1991 through
      April 2008. The cases of pediatric patients (aged < 20 years) were reviewed in
      detail. RESULTS: Of 123 patients with LyP identified, 14 (11%) were in the
      pediatric age group. Most were male (64%); mean age of onset was 12 years. Type A
      LyP was identified in 12 patients, one patient had type B, and none had type C
      (type not determined in one case). Ten cases showed CD8 predominance by
      immunohistochemistry. T-cell intracytoplasmic antigen staining was positive in 3
      cases of CD8(+) LyP type A and the one case of LyP type B. Lesional T-cell
      receptor gene rearrangement studies were negative in 9 of 10 patients with LyP
      type A. The average follow-up time was 5.5 years. Lesions improved with treatment
      in most cases, and none of the cases were associated with hematologic
      malignancies. LIMITATIONS: This was a retrospective review. CONCLUSIONS: Among
      our pediatric patients, we noted a predominance of CD8(+) LyP, which does not
      seem to have an aggressive course. Further longitudinal studies are necessary to
      evaluate prognostic differences between CD4(+) and CD8(+) LyP and their
      biological significance.

PMID- 19577332
TI  - Palisaded neutrophilic granulomatous dermatitis associated with systemic lupus
      erythematosus presenting with the burning rope sign.
AB  - Palisaded neutrophilic granulomatous dermatitis is a rare but increasingly
      recognized cutaneous manifestation of connective tissue disorders. It is reported
      most commonly with rheumatoid arthritis but also occasionally in association with
      systemic lupus erythematosus, inflammatory bowel disease, lymphoproliferative
      disorders, and systemic vasculitides. The clinicopathological presentation is
      highly variable, which has led to suggestions that it encompasses a number of
      distinct diseases. Most previous cases have reported only a single clinical and
      histologic manifestation of the condition within an individual. Here, we present
      a case of systemic lupus erythematosus-associated palisaded neutrophilic
      granulomatous dermatitis in which a striking evolution of both clinical and
      histologic features was observed during the course of 7 years, providing
      compelling evidence for the proposal that palisaded neutrophilic granulomatous
      dermatitis represents a disease spectrum rather than separate disease entities.

PMID- 19577331
TI  - The burden of vitiligo: patient characteristics associated with quality of life.
AB  - BACKGROUND: Vitiligo is commonly regarded as a harmless cosmetic skin problem in
      Western societies, and the importance of treating patients with vitiligo is often
      underestimated. OBJECTIVE: We sought to determine the clinical and
      sociodemographic variables that adversely affect the quality of life in adult
      patients with generalized vitiligo so that these variables can be considered in
      the treatment and care. METHODS: A total of 245 adult patients with generalized
      vitiligo completed two quality-of-life questionnaires (the Medical Outcomes Study
      36-Item Short-form General Health Survey and the Skindex-29). Physicians assessed
      sociodemographic and clinical characteristics of these patients. RESULTS: Dark
      skin type, vitiligo located on the chest, and treatment in the past appeared to
      have an adverse impact on the psychosocial domains of quality of life. Moreover,
      itch was reported by 20% of the patients in this study. LIMITATIONS: Psychiatric
      comorbidity was not evaluated in the analyses. CONCLUSION: Generalized vitiligo
      is a serious skin disorder with an adverse impact on the emotional state,
      comparable with that of other major skin diseases.

PMID- 19577333
TI  - Foot or hand malformations related to deep venous system anomalies of the lower
      limb in Klippel-Trenaunay syndrome.
AB  - BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a capillary-lymphatic-venous
      malformation associated with soft tissue and skeletal hypertrophy of one or more
      limbs. Deep venous system (DVS) anomalies are reported to be present in 8% to 18%
      of patients with KTS; approximately 25% of patients with KTS have hand or foot
      malformations. OBJECTIVE: We sought to assess whether the presence of hand or
      foot malformations in KTS is a predictor of DVS anomalies. METHODS: Retrospective
      data were collected from 51 consecutive patients with KTS seen in a university
      hospital between January 2000 and February 2008. Patients with possible Proteus
      syndrome were not included. The presence and patency of the DVS was studied using
      conventional venography, multidetector computed tomography, or fast 3-dimensional
      magnetic resonance imaging venography. RESULTS: Seventeen hand or foot
      malformations were present in 9 patients, consisting of: toe macrodactyly in 5
      patients (two bilateral and one with plantar expansion); toe microdactyly in one
      patient; finger macrodactyly in one patient; finger macrodactyly and ectrodactyly
      in one patient; syndactyly in 4 patients; and clinodactyly with camptodactyly of
      the hand of one patient with lower limb KTS. Eleven patients had DVS anomalies
      (one with aplasia of entire DVS; one with duplication of the superficial femoral
      vein; 7 with hypoplasia of femoral vein; and 7 with aplasia of the popliteal
      vein). All patients with hand or foot malformations also had DVS anomalies (P <
      .001). LIMITATIONS: Small sample size was a limitation. CONCLUSION: The presence
      of hand or foot malformations in KTS may predict the presence of DVS anomalies.

PMID- 19577334
TI  - Emergency department charges for evaluating minimally injured alcohol-impaired
      drivers.
AB  - STUDY OBJECTIVE: The literature on the costs of treating alcohol-impaired motor
      vehicle crash victims is largely based on inpatient data. Less is known about the
      more frequent emergency department (ED) evaluations for those who are discharged
      home. Our objective is to measure the difference in charges and length of stay
      between alcohol-impaired and nonimpaired drivers in this population. METHODS:
      This was a retrospective study of charts and billing data for all drivers in
      motor vehicle crashes, aged 21 to 65 years, treated at an urban Level I trauma
      center in 2005 and discharged home from the ED. Patients were divided into
      alcohol-positive and -negative groups according to alcohol level, documentation
      of recent alcohol use, or clinical intoxication. Itemized charges were tabulated
      and compared across groups. RESULTS: Of 1,618 eligible patients, median charges
      were higher for alcohol-positive patients by $4,538 (95% confidence interval [CI]
      $2,755 to $5,665). Imaging was 69% of the charge differential because of a higher
      frequency of imaging (91% versus 70%) and more expensive studies (median
      difference $2,464; 95% CI $1,507 to $3,400) for alcohol-positive patients. Median
      length of stay was higher for alcohol-positive patients by 3.3 hours (95% CI 2.7
      to 4.1 hours). When stratified by trauma-protocoled triage destination, median
      charges were higher for alcohol-positive versus -negative patients in non
      critical care beds by $2,229 (95% CI $1,039 to $2,693). For patients triaged to
      critical care beds, the difference in charges was only $132 (95% CI -$1,677 to
      $1,233). CONCLUSION: The presence of alcohol substantially increased charges and
      length of stay for ED evaluations of injured drivers discharged home, especially
      for patients who were triaged to non-critical care beds. The magnitudes are
      striking for this minimally injured population and represent an underreported
      burden of alcohol-impaired driving.

PMID- 19577335
TI  - Fatal toxic shock syndrome from an intrauterine device.
AB  - Toxic shock syndrome is a rare toxin-mediated condition that can rapidly produce
      multiorgan failure and severe shock. Toxic shock syndrome has been previously
      recognized in various clinical situations relating to surgery, nasal packing,
      abscesses, burns, and most notably menstrual-related cases. This case report
      describes a previously healthy 33-year-old woman presenting to the emergency
      department with complaints of nausea, vomiting, and diarrhea; vital signs at
      triage were normal. Within hours, she developed shock and cardiopulmonary arrest.
      The patient met all 6 of the Centers for Disease Control and Prevention
      diagnostic criteria for toxic shock syndrome, and her intrauterine device grew
      out Staphylococcus aureus. To our knowledge, this is the first reported case in
      the medical literature of fatal toxic shock syndrome related to an intrauterine
      device.

PMID- 19577337
TI  - [Gastric perforation associated with Candida infection].
AB  - Notable causes of gastroduodenal ulcer are Helicobacter pylori infection, intake
      of non-steroidal anti-inflammatory agents, neoplastic disease, acid
      hypersecretory states and secondary peptic ulcer disease. There are case reports
      of healthy patients or those with risk factors for fungal infection who develop
      gastroduodenal ulcer perforation associated with the presence of fungi in ascitic
      fluid or gastroduodenal ulcer tissue but without the above-mentioned etiological
      factors. Thus, other factors and pathogens may be involved in the pathogenesis of
      perforation. The use of antifungal agents in patients following surgery for a
      perforated gastroduodenal ulcer is controversial. We report two cases of healthy
      patients who underwent surgery for perforated gastroduodenal ulcer, in whom the
      most frequent causes of perforation were excluded. Only the presence of Candida
      in the ulcer was found.

PMID- 19577336
TI  - Peroxiredoxin II preserves cognitive function against age-linked hippocampal
      oxidative damage.
AB  - Reactive oxygen species (ROS), routinely produced in biological reactions,
      contribute to both normal aging and age-related decline in cognitive function.
      However, little is known regarding the involvement of specific antioxidants in
      the underlying mechanism(s). Here, we examined if peroxiredoxin II (Prx II)
      scavenges intracellular ROS that cause age-dependent mitochondrial decay in
      hippocampal CA1 pyramidal neurons and subsequent impairment of learning and
      memory. Age-dependent mitochondrial ROS generation and long-term potentiation
      (LTP) decline were more prominent in hippocampal neurons in Prx II(-/-) than in
      wild-type mice. Additionally, Prx II(-/-) mice failed to activate synaptic
      plasticity-related cellular signaling pathways involving CREB, CaMKII, and ERK,
      or to maintain functional integrity of their mitochondria. Dietary vitamin E
      alleviated Prx II deficiency-related deficits, including mitochondrial decay and
      CREB signaling, resulting in restoration of the abrupt cognitive decline in aged
      Prx II(-/-) mice. These results suggest that Prx II help maintain hippocampal
      synaptic plasticity against age-related oxidative damage.

PMID- 19577338
TI  - [Efficacy and safety of vaccination against hepatitis A and B in patients with
      chronic liver disease].
AB  - Vaccination to protect against hepatitis A and B should be part of the routine
      management of patients with chronic liver disease (CLD). OBJECTIVES: To evaluate
      the efficacy and safety of hepatitis A virus (HAV) and hepatitis B virus (HBV)
      vaccination in a group of patients with CLD and to assess the presence of factors
      predictive of response. PATIENTS AND METHODS: We performed a prospective, single
      center study in 194 patients (123 men, 71 women; mean age, 48.9+/-10.7 years)
      with CLD: 107 with chronic hepatitis (CH) and 87 with hepatic cirrhosis (HC), all
      Child-Pugh class A. The most frequent causes of CLD were HCV infection and
      alcohol. Patients negative for anti-HAV IgG received the HAV vaccination (1440
      ELISA units in two doses) and those with negative HBV serology received the HBV
      vaccination ( three 20 microg doses). Patients with inadequate response to the
      latter vaccine received an additional double dose. Thirty patients received a
      combination vaccine (three doses). RESULTS: Sixty patients (31%) received the HAV
      vaccine and 150 (77%) patients received the HBV vaccine. Seroconversion was
      achieved by 91.6% of patients for HAV and by 57% of the patients for HBV. After
      the additional dose, the response increased to 74%. Efficacy was similar between
      CH and HC. HBV vaccination was less effective in HC than in CH and the
      seroconversion rate was significantly lower in patients with HC and previous
      decompensation. The combination vaccine (30 patients) was highly immunogenic. No
      adverse effects were registered. CONCLUSIONS: HAV vaccination has high efficacy
      in patients with CLD. Patients with HC respond weakly to HBV vaccination compared
      with those with CH and especially if there is prior decompensation. The
      combination vaccine seems particularly effective in patients with CLD. The three
      vaccines are safe.

PMID- 19577340
TI  - [Chemical or immunological tests for the detection of fecal occult blood in
      colorectal cancer screening?].
AB  - Colorectal cancer (CRC) can be prevented by screening programs in the population
      at average risk (men and women aged between 50 and 74 years) and at high risk
      (first degree relatives, CRC hereditary syndromes and chronic inflammatory bowel
      disease). Early CRC (with submucosal invasion) and advanced adenomas (size > or
      =10mm, with severe dysplasia or >20% villous component) produce intermittent
      microscopic blood losses that can be detected through chemical and immunological
      testing for fecal occult blood (C-FOBT and I-FOBT). Among the screening
      strategies in the population at average risk, annual or biannual fecal occult
      blood testing is the most widely used due to its non-invasiveness and low cost.
      Four randomized clinical trials have shown that annual or biannual screening with
      guaiac-based tests (C-FOBT) reduces overall mortality due to CRC by 16% and CRC
      incidence by 20% and 17% respectively. However, these tests have major drawbacks,
      especially their low sensitivity in detecting early CRC and advanced adenoma,
      their lack of specificity in detecting human hemoglobin (Hb), and their high
      fecal Hb detection threshold (>300microgHb/gfeces). In the last few years, major
      developments have occurred in immunological tests (I-FOBT), based on an antigen
      antibody reaction that specifically detects human Hb, and these tests are
      currently available as an alternative to C-FOBT. Their main advantages are as
      follows: firstly, I-FOBT specifically detect human Hb in stools and at much lower
      levels (40-300microgHb/gfeces) than C-FOBT; secondly, automated analysis avoids
      subjectivity in reading qualitative tests and allows large population groups to
      be studied in a short time, making I-FOBT ideal for population-based screening;
      thirdly, I-FOBT fairly accurately selects individuals for colonoscopy so that
      approximately half of patients with an I-FOBT test show clinically significant
      colorectal neoplasia (advanced adenoma or invasive CRC); fourthly, the cut-off
      point for fecal Hb detection can be modified, depending on the availability of
      endoscopic resources; fifthly, when cut-off points for fecal Hb of 50
      150microgHb/gfeces are used, more than twice the number of CRC and advanced
      adenomas are detected than with C-FOBT, with a reasonable false-positive rate;
      and sixthly, I-FOBT are better accepted by the population due to their simplicity
      and ease of use, increasing participation in screening programs. For all these
      reasons, the current recommendation is that the new quantitative I-FOBT tests
      replace C-FOBT tests when the strategy of population-based screening through
      annual or biannual fecal occult blood testing is considered.

PMID- 19577341
TI  - [New techniques to extract impacted partially covered metallic biliary stents].
AB  - One of the problems affecting metallic biliary stents is the difficulty of
      removing them, especially after a period of months or if they have migrated.
      Several approaches have been used to remove both covered and uncovered stents,
      although with different degrees of effectiveness. We report two new approaches to
      removing partially covered stents that migrated proximally and that impacted in
      the papillary area and distal common bile duct. One stent was removed by
      papillectomy and the other by using duodenoscopy-guided controlled radial
      expansion balloon dilation. In both cases, the stents were removed without severe
      complications for the patient, leaving a good caliber in the stenosis.

PMID- 19577339
TI  - [Peritoneal tuberculosis due to Mycobacterium bovis in a cirrhotic patient].
AB  - Isolated peritoneal tuberculosis is an uncommon extrapulmonary form of
      presentation of tuberculosis in industrialized countries. In most cases, this
      disease is the result of reactivation and secondary hematogenous spread of a
      latent infection. Although the suspected diagnosis is given by clinical
      manifestations and analysis of ascitic fluid (lymphocytic predominance, albumin
      gradient between serum and ascitic fluid 1g/dl and adenosine deaminase
      concentration > or = 39 U/L), microbiologic assessment is required for the
      definitive diagnosis. Mycobacterium bovis causes tuberculosis in animals.
      Transmission to humans is rare in developed areas, given that it usually occurs
      through ingestion of unpasteurized contaminated milk. We present a patient with
      cirrhosis who developed ascites caused by an exceptional infection in our
      setting.

PMID- 19577342
TI  - [Effect of restricting amino acids except methionine on mitochondrial oxidative
      stress].
AB  - INTRODUCTION: Protein or methionine restriction in the diet is known to decrease
      reactive oxygen species (ROS) production and mitochondrial oxidative stress and
      to increase maximum longevity in rodents, which could explain how these changes
      also take place in dietary restriction. However, it is not known whether
      restriction of other amino acids is also involved. To clarify this question, we
      studied the effect of restricting all the amino acids, except methionine, of the
      semi-purified diet, AIN 93G, in Wistar rats. MATERIAL AND METHODS: Seven-week old
      male Wistar rats (n=16) were randomly divided into two groups: a control group
      and a group with 40% restriction of dietary amino acids except methionine. After
      7 weeks of dietary treatment, the animals were sacrificed and their livers were
      extracted to isolate mitochondria immediately and measure ROS production and
      oxygen consumption; these data allowed the percentage of free radical leak to be
      calculated. Oxidative damage to mitochondrial DNA was calculated as 8-oxo-7,8
      dihydro-2'-deoxyguanosine by HPLC-EC. RESULTS: At the end of the experimental
      period, a decrease in kidney weight was observed, but the weight of the liver,
      heart and brain was unchanged. ROS production in isolated liver mitochondria was
      unchanged with complex I (pyruvate/malate or glutamate/malate) or complex II
      (succinate) linked substrates. Maximum rates of ROS production significantly
      decreased with glutamate/malate+rotenone but not with pyruvate/malate+rotenone or
      with succinate. There were no changes in oxygen consumption with any substrate
      either in state 4 (resting) or in state 3 (phosphorylating). In agreement with
      the ROS production results, there were no differences between groups in oxidative
      damage to mitochondrial DNA. CONCLUSIONS: Taken together with previous results
      concerning methionine restriction, the results obtained in the present study
      clearly show that the decrease in ingestion of only one molecule, methionine,
      causes the decrease in ROS production and oxidative damage to mitochondrial DNA
      that is observed in dietary restriction in relation to the decrease in the rate
      of aging.

PMID- 19577343
TI  - [Medical short stay unit for geriatric patients in the emergency department:
      clinical and healthcare benefits].
AB  - INTRODUCTION: To evaluate the impact of comprehensive geriatric assessment and
      management of high-risk elders in a medical short stay unit located in the
      emergency department of a general hospital. MATERIAL AND METHODS: We performed a
      descriptive, prospective study of patients admitted to the medical short stay
      unit for geriatric patients of the emergency department in 2006. RESULTS: A total
      of 749 patients were evaluated, with a mean (standard deviation) stay in the unit
      of 37 (16) h. The mean age was 86 (7) years; 57% were women, and 50% had moderate
      severe physical impairment and dementia. Thirty-five percent lived in a nursing
      home. The most frequent reason for admission was exacerbation of chronic
      cardiopulmonary disease. Multiple geriatric syndromes were identified. The most
      frequent were immobility, pressure sores and behavioral disorders related to
      dementia. Seventy percent of the patients were discharged to home after being
      stabilized and were followed-up by the geriatric clinic and day hospital (39%),
      the home care medical team (11%), or the nursing home or primary care physician
      (20%). During the month after discharge, 17% were readmitted and 7.7% died,
      especially patients with more advanced age or functional impairment. After the
      unit was opened, admissions to the acute geriatric unit fell by 18.2%.
      CONCLUSIONS: Medical short stay units for geriatric patients in emergency
      departments may be useful for geriatric assessment and treatment of exacerbations
      of chronic diseases. These units can help to reduce the number of admissions and
      optimize the care provided in other ambulatory and domiciliary geriatric
      settings.

PMID- 19577344
TI  - Heterocyclic replacement of the central phenyl core of diamine-based histamine H3
      receptor antagonists.
AB  - A series of small molecules consisting of a heterocyclic core flanked by two
      basic functionalities were synthesized and screened for in vitro affinity at the
      human histamine H(3) receptor (hH(3)R). Nine of the twenty-eight compounds tested
      were found to possess a hH(3)R K(i) of less than 5 nM and consisted of a diverse
      range of central hetero-aromatic linkers (pyridine, pyrazine, oxazole, isoxazole,
      thiazole, furan, thiophene, and pyrrole). One member of this series, (4-isopropyl
      piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone (37), was found
      to be a high affinity, selective antagonist that crosses the blood-brain barrier
      and occupies H(3) receptors after oral administration in the rat.

PMID- 19577345
TI  - Measuring the radium-226 activity using a multidetector gamma-ray coincidence
      spectrometer.
AB  - The method is based on coincidence counting of the 609 keV photons from two-,
      three- and four-step cascade transitions which follow beta(-)-decay of (214)Bi,
      developed on the six-crystal spectrometer PRIPYAT-2M. As regards the
      determination of the activity of (226)Ra and its decay products, the double
      coincidences mode of counting is the optimum one because of the highest
      spectrometer sensitivity. Minimum detectable radium activity concentration in
      that mode of counting in a soil sample is estimated to be 0.68 Bq kg(-1) for live
      measuring time of 897.4s, while it was 2.03 Bq kg(-1) over 10 002.9s in the case
      of the HPGe spectrometer. Using the double coincidences method, the (226)Ra
      activity was determined in soil and sand samples from the Coastal region of
      Montenegro. The measurements were performed much faster than when an HPGe
      spectrometer is used, and the results showed relatively low level of the radium
      activity concentration.

PMID- 19577346
TI  - A statistical evaluation of the geogenic controls on indoor radon concentrations
      and radon risk.
AB  - ANOVA is used to show that approximately 25% of the total variation of indoor
      radon concentrations in England and Wales can be explained by the mapped bedrock
      and superficial geology. The proportion of the total variation explained by
      geology is higher (up to 37%) in areas where there is strong contrast between the
      radon potential of sedimentary geological units and lower (14%) where the
      influence of confounding geological controls, such as uranium mineralisation, cut
      across mapped geological boundaries. When indoor radon measurements are grouped
      by geology and 1-km squares of the national grid, the cumulative percentage of
      the variation between and within mapped geological units is shown to be 34-40%.
      The proportion of the variation that can be attributed to mapped geological units
      increases with the level of detail of the digital geological data. This study
      confirms the importance of radon maps that show the variation of indoor radon
      concentrations both between and within mapped geological boundaries.

PMID- 19577347
TI  - Proteinuria as a surrogate outcome in CKD: report of a scientific workshop
      sponsored by the National Kidney Foundation and the US Food and Drug
      Administration.
AB  - Changes in proteinuria have been suggested as a surrogate outcome for kidney
      disease progression to facilitate the conduct of clinical trials. This report
      summarizes a workshop sponsored by the National Kidney Foundation and US Food and
      Drug Administration (FDA) with the following goals: (1) to evaluate the strengths
      and limitations of criteria for assessment of proteinuria as a potential
      surrogate end point for clinical trials in chronic kidney disease (CKD), (2) to
      explore the strengths and limitations of available data for proteinuria as a
      potential surrogate end point, and (3) to delineate what more needs to be done to
      evaluate proteinuria as a potential surrogate end point. We review the importance
      of proteinuria in CKD, including the conceptual model for CKD, measurement of
      proteinuria and albuminuria, and epidemiological characteristics of albuminuria
      in the United States. We discuss surrogate end points in clinical trials of drug
      therapy, including criteria for drug approval, the definition of a surrogate end
      point, and criteria for evaluation of surrogacy based on biological plausibility,
      epidemiological characteristics, and clinical trials. Next, the report summarizes
      data for proteinuria as a potential surrogate outcome in 3 broad clinical areas:
      early diabetic kidney disease, nephrotic syndrome, and diseases with mild to
      moderate proteinuria. We conclude with a synthesis of data and recommendations
      for further research. At the present time, there appears to be sufficient
      evidence to recommend changes in proteinuria as a surrogate for kidney disease
      progression in only selected circumstances. Further research is needed to define
      additional contexts in which changes in proteinuria can be expected to predict
      treatment effect. We recommend collaboration among many groups, including
      academia, industry, the FDA, and the National Institutes of Health, to share data
      from past and future studies.

PMID- 19577348
TI  - Acute kidney injury during warfarin therapy associated with obstructive tubular
      red blood cell casts: a report of 9 cases.
AB  - Acute kidney injury (AKI) during warfarin therapy usually is hemodynamic
      secondary to massive blood loss. Here, we report pathological findings in kidney
      biopsy specimens from 9 patients with warfarin overdose, hematuria, and AKI.
      Kidney biopsy specimens from patients on warfarin therapy with AKI were
      identified in our database within a 5-year period. Each kidney biopsy specimen
      was evaluated by using semiquantitative morphometric techniques, and medical
      history was reviewed for conditions explaining AKI. Biopsy specimens with
      morphological findings of active glomerulonephritis and active inflammatory
      lesions were excluded from the study. Biopsy specimens from 9 patients were
      selected. At presentation with AKI, each patient had an abnormal international
      normalized ratio (mean 4.4 +/- 0.7 IU) and increased serum creatinine level
      (mean, 4.3 +/- 0.8 mg/dL). Morphologically, each biopsy specimen showed evidence
      of acute tubular injury and glomerular hemorrhage: red blood cells (RBCs) in
      Bowman space and numerous occlusive RBC casts in tubules. Each biopsy specimen
      showed chronic kidney injury. Six of 9 patients did not recover from AKI. These
      data suggest that warfarin therapy can result in AKI by causing glomerular
      hemorrhage and renal tubular obstruction by RBC casts. Our experience suggests
      that this may be a potentially serious complication of warfarin therapy,
      especially in older patients with underlying chronic kidney injury.

PMID- 19577349
TI  - Shared primacy of sodium and potassium on cardiovascular risk.

PMID- 19577350
TI  - Metabolic and hemodynamic advantages of an acetate-free citrate dialysate in a
      uremic case of congenital methylmalonic acidemia.

PMID- 19577351
TI  - Concurrent and discrete clinicopathological presentations of Wegener
      granulomatosis and anti-glomerular basement membrane disease.
AB  - About 30% of patients with anti-glomerular basement membrane antibody (anti-GBM)
      disease may also have concomitant antineutrophil cytoplasmic antibody (ANCA)
      positivity. Both these processes can affect the kidneys and/or lungs. We report a
      case of a patient with dual positivity for anti-GBM antibodies and ANCAs who
      underwent both pulmonary and kidney biopsies. There is only 1 previous report in
      the literature of a patient with dual positivity for anti-GBM antibodies and
      ANCAs who also underwent both pulmonary and kidney biopsies. Our case is unique
      in that our patient had dual positivity and also had evidence of unique tissue
      injury mediated by both antibodies in both the kidneys and lungs. We discuss the
      significance of dual-antibody positivity based on reported cases.

PMID- 19577352
TI  - Recurrent and relapsing peritonitis: causative organisms and response to
      treatment.
AB  - BACKGROUND: The clinical behavior and optimal treatment of relapsing and
      recurrent peritonitis episodes in patients undergoing long-term peritoneal
      dialysis are poorly understood. STUDY DESIGN: Retrospective study over 14 years.
      SETTING & PARTICIPANTS: University dialysis unit; 157 relapsing episodes (same
      organism or culture-negative episode occurring within 4 weeks of completion of
      therapy for a prior episode), 125 recurrent episodes (different organism, occurs
      within 4 weeks of completion of therapy for a prior episode), and 764 control
      episodes (first peritonitis episode without relapse or recurrence). PREDICTORS:
      Exit-site infection, empirical antibiotics. OUTCOME MEASURES: Primary response
      (resolution of abdominal pain, clearing of dialysate, and peritoneal dialysis
      effluent neutrophil count < 100 cells/mL after 10 days of antibiotic therapy),
      complete cure (resolution by using antibiotics without relapse/recurrence),
      catheter removal (for any cause while on antibiotic therapy), and mortality.
      RESULTS: Compared with the control group, more relapsing episodes were caused by
      Pseudomonas species (16.6% versus 9.4%) and were culture negative (29.9% versus
      16.4%); recurrent infections commonly were caused by Enterococcus species (3.2%
      versus 1.2%) or other Gram-negative organisms (27.2% versus 11.1%) or had mixed
      bacterial growth (17.6% versus 12.7%). There were significant differences in
      primary response, complete cure, and mortality rates among groups (P < 0.001 for
      all comparisons). Compared with the control and relapsing groups, post hoc
      analysis showed that the recurrent group had a significantly lower primary
      response rate (86.4%, 88.5%, and 71.2%, respectively), lower complete cure rate
      (72.3%, 62.4%, and 42.4%, respectively), and higher mortality rate (7.7%, 7.0%,
      and 20.8%, respectively). LIMITATIONS: Retrospective analysis. CONCLUSION:
      Relapsing and recurrent peritonitis episodes are caused by different spectra of
      bacteria and probably represent 2 distinct clinical entities. Recurrent
      peritonitis episodes had a worse prognosis than relapsing ones.

PMID- 19577353
TI  - Social capital and perceived health in Japan: an ecological and multilevel
      analysis.
AB  - Numerous empirical studies, largely conducted in Western societies, have linked
      social capital to health outcomes. However, few studies thus far have been
      conducted in northeastern Asian countries, particularly Japan. Therefore, whether
      social capital is a determinant of health in Japanese society remains unclear.
      This study attempted to provide new evidence for the impact of social capital on
      health in Japan by analyzing original survey data with two different statistical
      models. In total, 1910 subjects were randomly selected from 210 enumeration
      districts (EDs) considered in the 2000 population census. In the present study,
      after excluding missing data on the outcome and predictor variables, we conducted
      an analysis of 1157 individuals nested within 206 EDs. Ecological and multilevel
      regression analyses were performed to examine the association between social
      capital and health, measured by the General Health (GH) perception item (a
      subcategory of Short Form 36 (SF-36)), and to estimate the impact of aggregated
      indicators of social capital on health. We developed an original Japanese version
      of three social capital items (perceived helpfulness, kindness, and greeting)
      based on previous studies and expert opinions and prepared a social cohesion
      index that integrated these three social capital items. The ecological model,
      after adjusting for sociodemographic factors, revealed that perceived helpfulness
      and greeting, along with the social cohesion index, were observed to have
      statistically significant associations with GH. The multilevel model, after
      adjusting for individual social capital perceptions, indicated that the two
      aggregated indicators of community social capital (kindness and greeting), along
      with the social cohesion index, showed a statistically significant association
      with GH. These results showed the existence of a contextual effect of social
      capital on health outcomes, although individual differences in social capital
      perceptions in Japan were considered.

PMID- 19577354
TI  - No role for routine chest radiography in stage I seminoma surveillance.
AB  - BACKGROUND: After orchidectomy, the standard management options available for
      stage I seminoma are surveillance, adjuvant radiotherapy, or adjuvant
      chemotherapy. The optimal follow-up protocol for surveillance is yet to be
      determined but includes frequent chest radiography (CXR) and computed tomography
      (CT) scan of the abdomen and pelvis (CT-AP). OBJECTIVE: The purpose of this study
      was to identify the modality that first detected relapse and to assess the value
      of the CXR in this setting. DESIGN, SETTING, AND PARTICIPANTS: Five hundred
      twenty-seven patients with histologically confirmed stage I testicular seminoma
      were managed with surveillance at our institution between 1982 and 2005. Routine
      CXRs were performed with each CT-AP and were done every 4-6 mo for 7 yr and
      annually thereafter. The median follow-up was 72 mo (range: 1-193). MEASUREMENTS:
      Measurements included the 5-yr relapse rate, overall survival, and disease-free
      survival to determine the modality that first detected relapse disease. RESULTS
      AND LIMITATIONS: The 5-yr actuarial relapse rate for the 527 patients was 14%.
      The 5-yr disease-free survival and overall survival were 85.7% and 98.6%,
      respectively. Seventy-three patients (97.3%) had an abnormal CT-AP and a normal
      CXR at relapse. One patient (1.3%) had an abnormal CT-AP with pulmonary
      metastasis on CXR and CT chest scan, and one patient (1.3%) had a biopsy-proven
      inguinal node metastasis with a normal CXR. No patient had a normal CT-AP or
      physical examination with an abnormal CXR at relapse. This is a single-center
      retrospective study based on a relatively small number of relapses and may be
      subject to bias. Confirmation of these results from other studies would be useful
      for wider clinical applicability. CONCLUSIONS: All except one relapse were
      detected by CT-AP with no relapses detected on CXR alone; therefore, CXR may be
      omitted as routine imaging in surveillance protocols.

PMID- 19577356
TI  - Coma resulting from spontaneous intracranial hypotension treated with the
      epidural blood patch in the Trendelenburg position pre-medicated with
      acetazolamide.
AB  - A 62-year-old man had a new onset of severe, orthostatic headache which
      eventually progressed to a stupor and a coma 3 weeks later. A computed tomography
      (CT) scan showed bilateral chronic subdural haematoma and magnetic resonance
      imaging (MRI) of the brain showed the typical findings of spontaneous
      intracranial hypotension (SIH). After pre-medication with acetazolamide, he was
      treated with three lumbar autologous epidural blood patches (EBPs) and kept in
      the Trendelenburg position, with full recovery. The first lumbar autologous EBP
      was ineffective and the second was only partially effective because of incorrect
      execution of the procedure as shown by spinal neuroimaging examination post-EBP.
      A spinal neuroimaging examination post-EBP is therefore to be recommended in
      order to confirm the correct execution of procedure. Pre-medication with
      acetazolamide and keeping the patient in the Trendelenburg position could reduce
      the flow of spinal cerebrospinal (CSF) leak favouring sealing of the hole.

PMID- 19577355
TI  - Optimizing the approach for lymph node dissection during laparoscopic radical
      cystectomy.
AB  - BACKGROUND: Lymph node dissection (LND) for muscle-invasive bladder cancer is one
      of the integral steps of radical cystectomy. In addition to staging, adequate LND
      has been found to alter both the prognosis for and the course of the disease
      after radical cystectomy. OBJECTIVE: To point out several essential steps that
      provide optimal exposure for LND during laparoscopic radical cystectomy for
      muscle-invasive bladder cancer. DESIGN, SETTING AND PARTICIPANTS: From August
      2006 to September 2008, we performed 10 laparoscopic cystectomies with an
      extended LND using this approach at our institution. Patient and tumor
      characteristics, the anatomic extent of the LND, the number of lymph nodes
      examined, and the postoperative complications encountered were evaluated.
      SURGICAL PROCEDURE: Essential steps include (1) a modified five-trocar
      arrangement; (2) use of a 30 degrees telescope during LND; (3) prior complete
      mobilization of the sigmoid colon, allowing its retraction using an umbilical
      tape; (4) accomplishment of most of the bilateral LND from the right side; and
      (5) performance of LND after removal of the specimen. MEASUREMENTS: The primary
      end points were adequate intraoperative exposure of the template and number of
      lymph nodes retrieved. The secondary end point was evaluation of postoperative
      lymph node recurrence as an assessment of a complete LND. RESULTS AND
      LIMITATIONS: Mean total operative time was 512.5 min (range: 420-660), with a
      mean operative time of 143 min (range: 115-165) for the extended LND. Adequate
      exposure was successful in all 10 patients. The average number of lymph nodes
      examined was 25.5 (range: 19-32), with 4 nodes positive for metastasis. No
      patients had pelvic or lymph node metastasis at a mean follow-up of 14.8 mo
      (range: 4-30). Limitations included an analysis of a small series of patients.
      CONCLUSIONS: This new approach provides optimal exposure for an adequate
      laparoscopic LND during radical cystectomy, without any compromise.

PMID- 19577357
TI  - The planar cell polarity protein Van Gogh-Like 2 regulates tumor cell migration
      and matrix metalloproteinase-dependent invasion.
AB  - Van Gogh-Like 2 (VANGL2) is a planar cell polarity protein essential for
      collective migration during embryonic development, yet its contribution to tumor
      cell motility and invasion are unknown. We report for the first time that loss of
      VANGL2 in human cancer cells promotes efficient collective and directed migration
      and matrix metalloproteinase (MMP)-dependent ECM invasion. We show that VANGL2
      knockdown cells exhibit increased activation of secreted MMP2, higher levels of
      membrane-localized MMP14, and decreased cell-surface fibronectin. These important
      findings support the notion that planar cell polarity proteins act in
      coordination with known regulators of cancer cell migration to influence invasion
      and perhaps metastasis.

PMID- 19577358
TI  - Nutlin-3 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      induced apoptosis through up-regulation of death receptor 5 (DR5) in human
      sarcoma HOS cells and human colon cancer HCT116 cells.
AB  - MDM2 is a critical negative regulator of the p53 tumor suppressor protein.
      Recently, nutlins, small-molecule antagonists of MDM2, have been developed to
      inhibit the p53-MDM2 interaction and activate p53 signaling. The expressions of
      DR4 and DR5, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL) receptors, are regulated by p53. In this study, the combined effects of
      nutlin-3 and TRAIL on apoptosis were investigated in HOS and HCT116 cells, which
      express wild-type p53. Nutlin-3 and TRAIL synergistically enhanced apoptosis
      owing to their intrinsic and extrinsic pathway signals, respectively. The
      increase in the Bid expression level and the decrease in the expression levels of
      anti-apoptotic proteins, c-FLIP and XIAP, were involved in this apoptosis
      enhancement. Furthermore, nutlin-3 activated the DR5 promoter and increased the
      expression levels of DR5 at mRNA and protein levels. These results indicate that
      the combination, treated with nutlin-3 and TRAIL, is useful for apoptosis
      induction in malignant cells expressing wild-type p53.

PMID- 19577360
TI  - Iron-oxidation processes in an electroflocculation (electrocoagulation) cell.
AB  - The processes of iron oxidation in an electroflocculation cell were investigated
      for a pH range of 5-9 and electric currents of 0.05-0.4A (equivalent current
      densities of 8.6-69 A/m(2)). At all pH values and electric currents investigated,
      it was demonstrated and proven that for all practical purposes, the form of iron
      that dissolves from the anode is Fe(2+) (ferrous). The difference between the
      amount of theoretical dissolution as calculated by Faraday's law and the amount
      of observed dissolved iron ions may indicate two phenomena in electrochemical
      cells. The first is possible dissolution of the anode even without the operation
      of an electric current; this led to higher theoretical dissolution rates at lower
      pH. The second is the participation of some of the electrons of the electric
      current in reactions other than anode dissolution which led to lower theoretical
      dissolution rates at higher pH. Those other reactions did not lead to an increase
      in the local oxidation saturation level near the anode and did not affect iron
      oxidation rates in the electroflocculation processes. The oxidation rates of the
      dissolved Fe(2+) (ferrous) to Fe(3+) (ferric) ions in electroflocculation
      processes were strongly dependent on the pH and were similar to the known
      oxidation rates of iron in non-electrochemical cells.

PMID- 19577359
TI  - Zoledronic acid induces apoptosis and changes the TRAIL/OPG ratio in breast
      cancer cells.
AB  - Breast cancer has a propensity to metastasize to bone, thus causing pathological
      fractures. Bisphosphonates are established drugs in the treatment of bone
      metastasis that inhibit osteoclast activity and interrupt the vicious cycle of
      osteoclast-tumor cell interactions. We evaluated the direct effects of zoledronic
      acid on estrogen receptor (ER)-negative MDA-MB-231 and ER-positive MCF-7 breast
      cancer cells. While zoledronic acid (100 microM) inhibited MDA-MB-231 cell
      proliferation after 72 h, and induced apoptosis via activation of caspase-3 and 
      7, it had only minor effects on MCF-7 cells. In addition, zoledronic acid induced
      apoptosis by up-regulating TNF-related apoptosis-inducing ligand (TRAIL) in MDA
      MB-231 cells (p<0.01), but had no effect on the expression of its decoy receptor
      osteoprotegerin (OPG). In MCF-7 cells, both cytokines were suppressed by
      zoledronic acid. In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio
      in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine
      system is a bisphosphonate-responsive target in breast cancer.

PMID- 19577361
TI  - Kinetics and thermodynamics of beta-carotene and chlorophyll adsorption onto acid
      activated bentonite from Xinjiang in xylene solution.
AB  - The kinetics and thermodynamics of beta-carotene and chlorophyll adsorption from
      xylene solution onto acid-activated bentonite (AAB) within the temperature range
      65-95 degrees C were investigated. Adsorption of beta-carotene was described well
      with the Langmuir isotherm, whereas chlorophyll adsorption was determined well
      with the Freundlich isotherm, and the experimental data on chlorophyll adsorption
      were also fitted by the Langmuir isotherm to a certain extent, as reflected by
      correlation coefficients (R(2)) over 0.9865. In addition, the adsorption of beta
      carotene and chlorophyll onto AAB are favorable. The pseudo-second-order model
      was found to explain the kinetics of adsorption of both pigments more
      effectively. Increase of temperature enhanced the adsorption rate and equilibrium
      adsorption capacity of beta-carotene and chlorophyll on AAB. The activation
      energy for the sorption of beta-carotene and chlorophyll on AAB was 19.808 kJ/mol
      and 16.475 kJ/mol, respectively. The thermodynamic parameters DeltaH(theta),
      DeltaS(theta) and DeltaG(theta), computed from K(F) of the adsorption isotherm
      constant, were 21.766 kJ/mol, 92.244 J/ K mol and -9.554 kJ/mol respectively for
      the adsorption of beta-carotene on AAB at 65 degrees C, and for adsorption of
      chlorophyll on AAB at 65 degrees C were 31.051 kJ/mol, 93.549 J/K mol and -0.729
      kJ/mol, respectively. The adsorption of beta-carotene and chlorophyll in xylene
      solution on AAB was a spontaneous and endothermic process with increasing in the
      randomness at the solid-solution interface.

PMID- 19577362
TI  - Evaluation of ammonium removal using a chitosan-g-poly (acrylic acid)/rectorite
      hydrogel composite.
AB  - This paper concerns the removal of ammonium ions (NH(4)(+)) from aqueous solution
      using a hydrogel composite chitosan grafted poly (acrylic acid)/rectorite
      prepared from in situ copolymerization. The effects of rectorite content, contact
      time, pH, NH(4)(+) concentration and temperature on the adsorption capacity were
      discussed. Langmuir, Freundlich, Tempkin and Redlich-Peterson isotherms were used
      to describe the experimental data. The results indicate that the adsorption
      equilibrium can be achieved within 3-5 min and, the hydrogel composite has a
      higher adsorption capacity for NH(4)(+) in a wide pH levels ranged from 4.0 to
      9.0. No significant changes in the adsorption capacity are found over the
      temperature range studied. The adsorption mechanism of NH(4)(+) onto hydrogel
      composite was proposed, and the reusable ability of this hydrogel adsorbent was
      evaluated.

PMID- 19577363
TI  - An overview of landfill leachate treatment via activated carbon adsorption
      process.
AB  - Water scarcity and pollution rank equal to climate change as the most urgent
      environmental issue for the 21st century. To date, the percolation landfill
      leachate into the groundwater tables and aquifer systems which poses a potential
      risk and potential hazards towards the public health and ecosystems, remains an
      aesthetic concern and consideration abroad the nations. Arising from the steep
      enrichment of globalization and metropolitan growth, numerous mitigating
      approaches and imperative technologies have currently drastically been addressed
      and confronted. Confirming the assertion, this paper presents a state of art
      review of leachate treatment technologies, its fundamental background studies,
      and environmental implications. Moreover, the key advance of activated carbons
      adsorption, its major challenges together with the future expectation are
      summarized and discussed. Conclusively, the expanding of activated carbons
      adsorption represents a potentially viable and powerful tool, leading to the
      superior improvement of environmental conservation.

PMID- 19577365
TI  - Central sensitization needs sigma receptors.

PMID- 19577364
TI  - A prospective comparison of post-surgical behavioral pain scales in preschoolers
      highlighting the risk of false evaluations.
AB  - Four behavioral rating scales (BRS) (CHEOPS, CHIPPS, FLACC and OPS) assessing
      postoperative pain in children aged 1-7 years were studied to compare their
      psychometric properties, sensitivity and specificity. One hundred and fifty
      children included in this prospective longitudinal study were videotaped to
      analyze retrospectively peri-operative behaviors. Pain and anxiety were evaluated
      by children or by their parents prospectively. At the end of the study, four
      observers rated the peri-operative videos using the four BRS. Because self
      reporting cannot be used for all the children, facial expression of pain was
      analyzed from the videos to create a Facial Action Summary Score (FASS) which was
      considered as a reference for the study of validity of the four BRS. Internal
      validities were excellent but external validities were mixed. The FLACC seems to
      be better adapted to assess post-surgical pain in children between 1 and 7 years
      old. Nevertheless, it was significantly correlated with anxiety measures.
      Moreover, the analysis of sensitivity and specificity using both self-reporting
      of pain and FASS showed that some children were still under-evaluated. The
      multivariate analysis underlines silence as a high risk factor of misevaluating
      postoperative pain. In conclusion, this study highlights the difficulty of
      discriminating pain intensity from anxiety when using the four BRS and that
      postoperatively, nearly one child in 10 was misevaluated.

PMID- 19577366
TI  - In vivo silencing of the Ca(V)3.2 T-type calcium channels in sensory neurons
      alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy.
AB  - Earlier, we showed that streptozocin (STZ)-induced type 1 diabetes in rats leads
      to the development of painful peripheral diabetic neuropathy (PDN) manifested as
      thermal hyperalgesia and mechanical allodynia accompanied by significant
      enhancement of T-type calcium currents (T-currents) and cellular excitability in
      medium-sized dorsal root ganglion (DRG) neurons. Here, we studied the in vivo and
      in vitro effects of gene-silencing therapy specific for the Ca(V)3.2 isoform of T
      channels, on thermal and mechanical hypersensitivities, and T-current expression
      in small- and medium-sized DRG neurons of STZ-treated rats. We found that
      silencing of the T-channel Ca(V)3.2 isoform using antisense oligonucleotides, had
      a profound and selective anti-hyperalgesic effect in diabetic rats and is
      accompanied by significant down-regulation of T-currents in DRG neurons. Anti
      hyperalgesic effects of Ca(V)3.2 antisense oligonucleotides in diabetic rats were
      similar in models of rapid and slow onset of hyperglycemia following intravenous
      and intraperitoneal injections of STZ, respectively. Furthermore, treatments of
      diabetic rats with daily insulin injections reversed T-current alterations in DRG
      neurons in parallel with reversal of thermal and mechanical hypersensitivities in
      vivo. This confirms that Ca(V)3.2 T-channels, important signal amplifiers in
      peripheral sensory neurons, may contribute to the cellular hyperexcitability that
      ultimately leads to the development of painful PDN.

PMID- 19577368
TI  - Influence of thick crystal effects on ptychographic image reconstruction with
      moveable illumination.
AB  - The properties of the iterative phase-retrieval ptychographical imaging technique
      are modelled. We use the multi-slice method to generate a series of diffraction
      patterns when a small convergent illumination spot is moved across a silicon
      crystal orientated in the 100 direction. These are then used to reconstruct the
      transmission function of the sample by solving the phase of diffraction patterns
      using the ptychographical iterative engine (PIE) algorithm [H.M.L. Faulkner, J.M.
      Rodenburg, Physical Review Letters 93 (2004) 023903], which assumes the object is
      a thin, two-dimensional grating. It is found that to obtain lattice-resolved
      reconstructions, the thickness of the crystal should be smaller than half of the
      corresponding extinction distance, the probe should be highly defocused to obtain
      a planar enough wave front and the movements of the probe should be as small as
      possible to minimize the changes in the transmission function of the sample for
      two adjacent illumination positions.

PMID- 19577367
TI  - Prefrontal cortex and spinal cord mediated anti-neuropathy and analgesia induced
      by sarcosine, a glycine-T1 transporter inhibitor.
AB  - Sarcosine is a competitive inhibitor of glycine type 1 transporter. We
      hypothesized that it may have analgesic and anti-neuropathic efficacy by a dual
      action: affecting neurotransmission in the prefrontal cortex as well as within
      the spinal cord. In rats with spared nerve injury (SNI) oral sarcosine reduced
      mechanical sensitivity for the injured limb (anti-neuropathy or anti-allodynia)
      as well as for the uninjured limb (analgesia), showing better dose efficacy for
      the injured limb. Intrathecal administration of sarcosine was more effective in
      reducing mechanical sensitivity for the uninjured paw. In contrast, prefrontal
      cortex infusions of sarcosine acutely reduced mechanical sensitivity for the
      injured paw. Repeated daily oral sarcosine induced anti-neuropathy, observed only
      after days of repeated treatment; this long-term effect disappeared a few days
      after treatment cessation. The findings indicate that manipulating glycine-T1
      transporter at multiple central sites can induce acute analgesia, as well as
      acute and long-term reduction in neuropathic pain behavior. Analgesic effects
      seem primarily mediated through spinal cord circuitry while anti-neuropathic
      effects seem mediated through prefrontal cortex circuitry, most likely through
      distinct molecular pathways. The results suggest that such an approach may
      provide a novel venue for treating clinical pain conditions.

PMID- 19577370
TI  - High prevalence of Theileria sp. in wild Chinese Water Deer (Hydropotes inermis
      argyropus) in South Korea.
AB  - Wild Chinese Water Deer exist in large numbers in Northeast Asia, including South
      Korea. The deer population is so widespread that they are common even in urban
      areas, resulting in increased contact with humans and domestic animals. The
      purpose of this study was to examine the prevalence of Theileria sp. infection in
      wild Chinese Water Deer in South Korea. Using biomolecular techniques, blood
      samples taken from 18 wild Chinese Water Deer were examined. Thirteen of the 18
      samples (72%) tested positive for infection. In 11 of the deer, a Theileria sp.
      was detected that is nearly identical to the highly pathogenic Theileria sp.
      reported in China. Theileria ovis and Theileria capreoli were also detected
      individually in two deer. These results indicate that there may be a high
      prevalence of Theileria sp. infection in wild Chinese Water Deer, and that the
      deer may act as a reservoir for the Theileria sp. infection of domestic animals.

PMID- 19577369
TI  - Comparative efficacy of oil solution and wettable powder of lambda-cyhalothrin to
      naturally occurring Ornithonyssus sylviarum infestation of chickens.
AB  - The Northern Fowl Mite (NFM), Ornithonyssus sylviarum, is one of the most
      important and common pests of poultry. Most of available pesticides applied in
      the NFM control are formulated as wettable powder or emulsifiable concentrate and
      require to be diluted with water before use. As water has very low affinity to
      bird feathers, a part of the diluted pesticide will fall on the ground, on the
      cages, on feed bins or drift in the air upon application, which becomes a source
      of a potential harm to administrative workers and birds. In contrast to water, an
      oil solution of pesticide has a higher affinity for feathers and can stay on the
      feather for a longer time, and maybe provide a high efficacy and be effective for
      a longer, persistent period against the NFM. In the present study, the efficacy
      of oil solution and wettable powder of lambda-cyhalothrin to NFM in breeders was
      compared; the results showed that while spraying lambda-cyhalothrin wettable
      powder on birds could effectively control NFM, painting lambda-cyhalothrin oil
      solution on birds gave complete control of NFM for at least 6 weeks. In the
      application of lambda-cyhalothrin oil solution, no containment of pesticide to
      cages, feed bin and no pesticide drifting in the air was observed. These results
      indicated that lambda-cyhalothrin oil solution has a potential to become an
      effective and safe formulation to control NFM in breeders.

PMID- 19577371
TI  - Development of a nursing workload measurement instrument in burn care.
AB  - Existing workload measurement instruments fail to represent specific nursing
      activities in a setting where patients are characterized by a diversity of cause,
      location, extent and depth of burns, of age and of history. They also do not
      include educational levels and appropriate time standards. The aim of this study
      was to develop a reliable measurement instrument for nursing workload in burn
      care, in order to match quality of patient care with staffing needs. In the first
      phase, a time study by semi-structured interviews and observations was used to
      assess direct and indirect care activities. A total of 34 nursing activities were
      identified, defined, connected to educational levels and attached to time
      standards. Two independent raters completed a test computer program by assessing
      performed nursing activities in 36 patients. This yielded intra-class
      correlations of 0.82, indicating good reliability. In the second phase, a
      computer program was developed to process quantity and quality of available staff
      and the sum of time standards of nursing activities per patient per day and to
      calculate the balance. After 1 year of running this program, the database was
      used to distinguish patients' care demand into five care categories. This
      instrument justifies the investment of time by nursing staff needed for daily
      activities in the burn unit. It provides quick insight into the balance between
      care demand and staffing needs and can be used to optimise resource planning.

PMID- 19577372
TI  - Burn injuries due to Christian religious customs.

PMID- 19577373
TI  - Wound-healing activity of a proteolytic fraction from Carica candamarcensis on
      experimentally induced burn.
AB  - Carica candamarcensis is a species from the Caricaceae family whose immature
      fruit contains latex with large amounts of cysteine proteinases. In prior
      studies, we isolated two of these enzymes displaying mitogenic activity when
      incubated with L929 fibroblastic cells. One of the fractions containing these
      enzymes (P1G10) was shown to enhance wound healing of skin and to accelerate
      healing of chemically induced gastric ulcer. In this study we evaluate the effect
      of P1G10 on heat-induced, third-degree burn using a rodent model. The results
      show that 0.1% P1G10 accelerates epithelisation while the effect of 1% or 0.01%
      P1G10 is not significantly different to 1% silver sulphadiazine, 2% papain or the
      hydrosoluble vehicle used as control. In a double-blind randomised experiment
      comparing the healing response of 0.1%, 1% and the vehicle alone, we confirmed
      the enhanced healing property of P1G10. Histological analysis of burn-tissue
      sections following treatment with P1G10 support these observations. These results
      extend the healing properties of these groups of enzymes to a different type of
      trauma and open the way to future clinical applications.

PMID- 19577374
TI  - Trapeze-flap plasty: effective method for postburn neck contracture elimination.
AB  - The new method for postburn neck contracture management is presented. The method
      is found to be most effective when using the local flap procedures on patients
      who cannot undergo complex and long surgical procedures that are aimed at both
      contracture elimination and neck skin restoration (children, elderly patients,
      patients with inadequate donor sites, and patients with cosmetically acceptable
      scar appearance). The method consists of the opposite transposition of trapezoid
      scar-fascial flaps which are prepared one on each antero-lateral neck surface.
      Both flaps include scars, fat, platysma and deep cervical fascia. As a result of
      the trapeze-flap plasty, the anterior surface of the neck is lengthened
      approximately by 100-200%, the contracture is eliminated and mentocervical angle
      and head movement are restored. The flaps have reliable blood circulation through
      the superficial cervical artery perforators, therefore flap loss is rare. The
      functional results were good in 24 out of 26 patients. The flaps surface does not
      decrease; therefore, the mild contracture becomes an exception.

PMID- 19577376
TI  - Cerebrospinal fluid oxytocin, life history of aggression, and personality
      disorder.
AB  - BACKGROUND: Data from animal studies have identified oxytocin as an important
      modulator of social aggression. We have previously reported on a relationship
      between cerebrospinal fluid (CSF) levels of vasopressin and life history of
      aggressive behavior, a finding that is consistent with animal data. We
      hypothesized that CSF Oxytocin levels would be inversely related to dimensional
      measures of lifetime aggression. METHODS: Lumbar CSF for morning basal levels of
      oxytocin was obtained from 58 consenting subjects with and without DSM-IV
      personality disorders. Aggression was assessed dimensionally using an interview
      instrument (Life History of Aggression (LHA)). The primary analysis was conducted
      using a linear regression model predicting variance in CSF Oxytocin
      concentration, including the predictors of LHA score, Sex, Height, and the
      presence or absence of personality disorder. RESULTS: The model predicting
      variance in CSF Oxytocin concentration including LHA score was statistically
      significant, after removal of a single multivariate outlier. Inclusion of the
      outlier resulted in a most likely spurious interaction between Sex and LHA score.
      Presence or absence of personality disorder was not associated with variance in
      CSF Oxytocin levels. Exploratory analyses revealed a possible inverse
      relationship between CSF Oxytocin level and history of suicidal behavior.
      CONCLUSIONS: As hypothesized, CSF Oxytocin levels were inversely correlated with
      life history of aggression. This represents the first such report of a
      relationship between oxytocin levels and aggression. The correlational, cross
      sectional study design precludes causal inferences, but the data are consistent
      with the known effects of oxytocin on aggressive behavior in animals.

PMID- 19577377
TI  - A "mini-fast with exercise" protocol for fat loss.
AB  - From the standpoint of promoting leanness, exercise is of most value if oxidation
      of stored fat is maximized during and following the exercise sessions. Bahadori
      has proposed that this can best be achieved if prolonged exercise of moderate
      intensity is performed during a 12-14 h "mini-fast" that entails skipping a meal;
      if subsequent food consumption features low-fat foods, the fat stores expended
      during and after the exercise will not be fully repleted by dietary fat. Thus,
      prolonged compliance with such a regimen should lead to steady loss of body fat
      until a much leaner equilibrium body composition is attained. The feasibility and
      efficacy of this strategy has been examined in an open pilot study. Participants
      were asked to perform prolonged, moderate-intensity aerobic exercise at least 3-5
      times weekly, nesting each exercise session within a 12-14 h mini-fast. No
      restrictions were placed on daily calorie consumption, but low-fat, low-glycemic
      index food choices were recommended. Of the 34 subjects originally enrolled, 27
      returned for follow-up evaluations at 6 and 12 weeks. During the 12 week study,
      the average fat loss in these 27 subjects - 7.4 kg - corresponded to one-quarter
      of their baseline fat mass. Fasting insulin levels likewise fell by 25%. The rate
      of fat loss was at least as great in the second 6 weeks as in the first,
      suggesting that fat loss might have persisted for some time if the study had been
      prolonged. This protocol, combining elements of exercise training, fasting, and
      low-fat eating, is both sustainable and healthful, and in reasonably compliant
      subjects may have considerable potential for promoting and maintaining leanness
      and insulin sensitivity.

PMID- 19577378
TI  - Support for the hypothesis that electro-stimulation is responsible for
      Lipoatrophia semicircularis.
AB  - Lipoatrophia semicircularis (L.s.) is a idiopathic condition characterised by
      semicircular impressions of the skin, usually at the front and sides of both
      thighs. It was first described some 35years ago but only as a case study where a
      few subjects with L.s. were described. Later on some more cases were diagnosed
      and described but their number remained low. It is only over the past ten years
      that an outburst of L.s. was observed. This was first seen in Belgium, later on
      also in other countries (e.g., Spain) where several hundreds of individuals were
      diagnosed with L.s. All these subjects belonged to the administrative personnel
      of diverse companies indicating that this condition is essentially office and job
      related. Afflicted subjects were mainly women working with computers or with
      other electrical devices placed on their desk. Furthermore, L.s. was invariably
      diagnosed after moving into new or renovated office buildings. Hypotheses have
      been put forward to explain the appearance of L. semicircularis. These hypotheses
      involve mechanical pressure, blood circulation problems, disturbance of thermal
      energy exchange and electrostatic discharges or other electric phenomena. In this
      paper, these hypotheses are considered and new data presented in favour of an
      "electric" origin of L.s. Earlier published observations on the influence of
      electric fields from 50Hz, 230V electrical cables and cables for data
      transmission remain valid, whereas other hypotheses seem to be invalidated by
      experience. The fact that for example electric devices are a constant factor in
      the appearance of L.s., that the cable type apparently plays an important role as
      well as the electric conductivity of the desktops on which L.s. subjects are
      sitting and that the presence of ionisators and the ambient relative humidity
      also proved to be determinative are arguments that the electric environment is on
      the origin of the L.s. condition. However, evidence was obtained that L.s. is
      most probably not related to electrostatic discharges but other phenomena of
      electro-stimulation are nevertheless possible. For example, formation of
      atmospheric air ions at the edge of the desk or on dust particles on their
      surface and consequently charging of the skin followed by discharges in the skin
      may be proposed as the main cause of L. semicircularis. This means that it is
      essential to control the electric environment of offices to minimize the risk of
      L. semicircularis.

PMID- 19577375
TI  - Are neuroactive steroids promising therapeutic agents in the management of acute
      and chronic pain?
AB  - Neuroactive steroids with potentiating effects on GABA(A) channels and inhibitory
      effects on T-type Ca2+ channels which are located in peripheral sensory neurons
      are potent modulators of pain perception. The focus of this review is on
      peripheral anti-nociceptive properties of 5alpha- and 5beta-reduced neuroactive
      steroids with either selective or combined modulatory action on GABA(A) and T
      type Ca2+ channel-mediated neurotransmission. We report that these neuroactive
      steroids are very effective in alleviating peripheral nociception in both acute
      and chronic pain conditions in animal models of pain. We believe that promising
      animal data warrant the exploration of their usefulness in clinical settings
      especially considering the fact that chronic pain sufferers are often young and
      otherwise healthy people.

PMID- 19577379
TI  - Potential complementarity of high-flavanol cocoa powder and spirulina for health
      protection.
AB  - Recent studies show that ingestion of flavanol-rich cocoa powder provokes
      increased endothelial production of nitric oxide - an effect likely mediated by
      epicatchin - and thus may have considerable potential for promoting vascular
      health. The Kuna Indians of Panama, who regularly consume large amounts of
      flavanol-rich cocoa, are virtually free of hypertension and stroke, even though
      they salt their food. Of potentially complementary merit is the cyanobacterium
      spirulina, which has been used as a food in certain cultures. Spirulina is
      exceptionally rich in phycocyanobilin (PCB), which recently has been shown to act
      as a potent inhibitor of NADPH oxidase; this effect likely rationalizes the broad
      range of anti-inflammatory, cytoprotective, and anti-atherosclerotic effects
      which orally administered spirulina has achieved in rodent studies. In light of
      the central pathogenic role which NADPH oxidase-derived oxidant stress plays in a
      vast range of disorders, spirulina or PCB-enriched spirulina extracts may have
      remarkable potential for preserving and restoring health. Joint administration of
      flavanol-rich cocoa powder and spirulina may have particular merit, inasmuch as
      cocoa can mask the somewhat disagreeable flavor and odor of spirulina, whereas
      the antioxidant impact of spirulina could be expected to amplify the bioactivity
      of the nitric oxide evoked by cocoa flavanols in inflamed endothelium. Moreover,
      there is reason to suspect that, by optimizing cerebrovascular perfusion while
      quelling cerebral oxidant stress, cocoa powder and spirulina could collaborate in
      prevention of senile dementia. Thus, food products featuring ample amounts of
      both high-flavanol cocoa powder and spirulina may have considerable potential for
      health promotion, and merit evaluation in rodent studies and clinical trials.

PMID- 19577380
TI  - New insights in atherosclerosis: endothelial shear stress as promoter rather than
      initiator.
AB  - The etiology of focal distribution of atherosclerotic lesions has received much
      attention for many years. Current theories focus on mechanical factors such as
      low endothelial shear stress as an initiating factor for atherosclerosis
      formation. However, some evidences revealed that it could not be initiator of
      endothelial damage. We hypothesize that endothelial damage results from the
      fatigue effect of pulse pressure on endothelial layer. In our model, heart rate,
      magnitude of pulse pressure, geometry and chemical environment of endothelial
      layer determine the rate of endothelial damage accumulation, and low endothelial
      shear stress acts as promoter of atherosclerosis rather than initiator. If this
      model is correct, it can provide a framework for speculating about the risk of
      endothelial stress rupture in the population as a whole and in patients undergone
      arterial grafting procedures, and how this might be reduced.

PMID- 19577381
TI  - Primary embryonal spindle cell cardiac rhabdomyosarcoma: case report.
AB  - Primary cardiac tumors are rare. Of all primary heart neoplasms, sarcomas account
      for around 10%, and of these, rhabdomyosarcomas (RMS) constitute a minority. A
      case of primary left atrial RMS, reminiscent of leiomyosarcoma, is reported
      herein. Histologically, the tumor was composed of tightly-packed spindle-shaped
      cells arranged in long fascicles. At immunohistochemistry, the tumor cells
      stained strongly and diffusely with vimentin, muscle-specific actin, desmin and
      myogenin, and focally with fast-myosin and sarcomeric actin. WT-1 showed diffuse
      and intense cytoplasmic staining. Staining for calponin was weak. Staining for
      alpha-SMA, H-caldesmon, CD34, epithelial membrane antigen (EMA), keratin wide
      spectrum (CK w.s.), and S100 protein was negative. Electron microscopy revealed
      poorly differentiated spindle cells, containing contractile filaments with a "Z
      band-like" appearance. The final diagnosis was embryonal RMS, spindle cell
      variant. Conclusively, spindle cell RMS is a well-recognized variant of embryonal
      RMS, typically occurring in soft tissue, with only rare cases described in
      visceral organs. This is the first case of primary cardiac spindle cell RMS ever
      described.

PMID- 19577382
TI  - Mixed ovarian large cell neuroendocrine carcinoma, mucinous adenocarcinoma, and
      teratoma: a report of two cases and review of the literature.
AB  - Large cell neuroendocrine carcinoma of the ovary is a rare recently established
      entity. Few cases have been reported in the literature, and they are usually
      associated with another type of surface epithelial tumor. The association of a
      large cell neuroendocrine carcinoma with a surface epithelial tumor and a
      teratoma is even rarer, with only two cases previously described. We report the
      cases of two patients in their fifties who presented with a growing abdominal
      mass and died of metastatic disease within less than a year. Histological
      assessment revealed large cell neuroendocrine carcinoma admixed with mucinous
      adenocarcinoma and teratoma. Different hypotheses regarding the origin of large
      cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical
      pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the
      composite epithelial tumors originated from the pre-existing teratoma.

PMID- 19577383
TI  - [Does sexuality still have a place for couples treated with assisted reproductive
      techniques?].
AB  - METHOD: This research enabled us to study the links between the diagnosis of
      infertility, medical care and the sexuality of the couples treated with Assisted
      Reproductive Techniques (ART). QUESTIONNAIRE/PATIENTS: The impact of infertility
      has been observed in various fields related to sexual intercourse: sexual desire
      and satisfaction, frequency of intercourse, sexual disorders as well as marital
      relationship and more generally the patient's experience of this medical follow
      up. These effects were studied in the light of various factors, such as sex and
      age, number of children and years of ART as well as the type of protocol and the
      origin of infertility. RESULTS: Our study reveals that the marital relationship
      is preserved as well as the pleasure felt during intercourse. However, the
      couples express a reduction of their sexual desire, linked to a loss of
      spontaneity that can be related to the strategies they set up to maximize their
      chances of pregnancy and to medical care.

PMID- 19577384
TI  - A multiplex RT-PCR assay for the rapid and differential diagnosis of classical
      swine fever and other pestivirus infections.
AB  - Classical swine fever is a highly contagious viral disease causing severe
      economic losses in pig production almost worldwide. All pestivirus species can
      infect pigs, therefore accurate and rapid pestivirus detection and
      differentiation is of great importance to assure control measures in swine
      farming. Here we describe the development and evaluation of a novel multiplex,
      highly sensitive and specific RT-PCR for the simultaneous detection and rapid
      differentiation between CSFV and other pestivirus infections in swine. The
      universal and differential detection was based on primers designed to amplify a
      fragment of the 5' non-coding genome region for the detection of pestiviruses and
      a fragment of the NS5B gene for the detection of classical swine fever virus. The
      assay proved to be specific when different pestivirus strains from swine and
      ruminants were evaluated. The analytical sensitivity was estimated to be as
      little as 0.89TCID(50). The assay analysis of 30 tissue homogenate samples from
      naturally infected and non-CSF infected animals and 40 standard serum samples
      evaluated as part of two European Inter-laboratory Comparison Tests conducted by
      the European Community Reference Laboratory, Hanover, Germany proved that the
      multiplex RT-PCR method provides a rapid, highly sensitive, and cost-effective
      laboratory diagnosis for classical swine fever and other pestivirus infections in
      swine.

PMID- 19577385
TI  - Relation between leptin and estradiol levels in Egyptian lactating Arab mares
      during foaling heat.
AB  - Sixteen Arab lactating mares belonging to Al-Zahraa Arab Horse Stud underwent two
      ultrasound examinations at 3 weeks interval starting from the day of
      demonstration of foaling heat. In addition, daily blood samples were collected
      from parturition until after exhibiting first postpartum estrus (day 11) with
      daily observation of estrous signs. Both leptin and estradiol hormones were
      assayed. Mean day of foaling heat was 8.9+/-0.9 day. Most mares came in foaling
      heat during days 9 and 10 had high conception rate compared to those who came in
      estrus earlier or later. Estradiol levels were high after day of foaling then
      decrease after expression of foaling heat. But leptin levels increase from day 8
      to day 10 compared to other days before and after the first ovulation. A
      significant positive correlation was found between estradiol and leptin (r=0.58,
      p<0.025). The positive correlation between leptin and estradiol led us to suggest
      that leptin hormone plays an important role in ovulation of the first postpartum
      estrus in mares.

PMID- 19577386
TI  - Aromatase inhibitors in breast cancer.
AB  - Estrogens play important roles in breast cancer development and progression. In
      postmenopausal women, traditional endocrine therapies such as tamoxifen have
      sought to inhibit estrogen action by targeting the estrogen receptor itself.
      However, newer treatments are evolving that target estrogen production in
      postmenopausal tissues through inhibition of the aromatase enzyme. Clinical data
      demonstrate that these aromatase inhibitors are superior to tamoxifen as adjuvant
      therapy for breast cancer and have now replaced tamoxifen as first line therapy
      in a number of treatment regimens for postmenopausal breast cancer patients.

PMID- 19577387
TI  - Reference study on the time frame for ossification of the distal radius and ulnar
      epiphyses on the hand radiograph.
AB  - Hand radiographs from 554 male and 288 female subjects aged 10-30 years, which
      had been taken due to traumatological indications, were evaluated. A
      classification into five ossification stages was applied to assess the epiphyseal
      development of distal radius and distal ulna (1: epiphysis not ossified; 2:
      epiphysis ossified, nonunion of the epiphysis and metaphysis; 3: partial union of
      the epiphysis and metaphysis; 4: complete union of the epiphysis and metaphysis,
      epiphyseal scar visible; 5: complete union of the epiphysis and metaphysis,
      epiphyseal scar nondiscernable). It was established that male subjects with an
      ossification stage 4 of the radius or ulna and female subjects with an
      ossification stage 5 of the radius were at least 14 years old. The occurrence of
      ossification stage 5 of the radius proves that a male individual has reached the
      age of 18 years.

PMID- 19577388
TI  - Comparative multibody dynamics analysis of falls from playground climbing frames.
AB  - This paper shows the utility of multibody dynamics in evaluating changes in
      injury related parameters of the head and lower limbs of children following falls
      from playground climbing frames. A particular fall case was used as a starting
      point to analyze the influence of surface properties, posture of the body at
      impact, and intermediate collisions against the climbing frame before impacting
      the ground. Simulations were made using the 6-year-old pedestrian MADYMO rigid
      body model and scaled head contact characteristics. Energy absorbing surfaces
      were shown to reduce injury severity parameters by up to 30-80% of those of rigid
      surfaces, depending on impact posture and surface. Collisions against components
      of a climbing frame during a fall can increase injury severity of the final
      impact of the head with the ground by more than 90%. Negligible changes are
      associated with lower limb injury risks when different surfacing materials are
      used. Computer reconstructions of actual falls that are intended to quantify the
      severity of physical injuries rely on accurate knowledge of initial conditions
      prior to falling, intermediate kinematics of the fall and the orientation of the
      body when it impacts against the ground. Multibody modelling proved to be a
      valuable tool to analyze the quality of eyewitness information and analyze the
      relative injury risk associated with changes in components influencing fall
      injuries from playground climbing frames. Such simulations can also support
      forensic investigations by evaluating alternative hypotheses for the sequence of
      kinematic motion of falls which result in known injuries.

PMID- 19577389
TI  - 3D analysis of spontaneous nystagmus in early stage of vestibular neuritis.
AB  - OBJECTIVE: The pathological localization of vestibular neuritis is still
      controversial. Analyses of the spontaneous nystagmus support the temporal bone
      studies, which indicated the location of the pathology to be in the superior
      vestibular nerve. However, based on the data from the head impulse testing the
      pathology is in the vestibular nerve including the inferior branch. METHODS:
      Twenty-three patients with vestibular neuritis participated in this study. The
      spontaneous nystagmus was recorded within 1 week after the onset of the disease.
      Three-dimensional analysis of the nystagmus was performed using video image
      analysis system. The rotation axis was calculated and compared to the anatomical
      axes of the semicircular canals. RESULTS: The axes of the spontaneous nystagmus
      in all patients were scattered around the axes of horizontal and anterior canals,
      especially between the compound axis of anterior and horizontal canals and the
      axis of horizontal canal. The statistical analysis revealed that in the quite
      early stage of the disease (day 0-2 of the attack), the spontaneous nystagmus
      tended to have more torsional eye movements as compared to the less early stage
      (day 3-6). CONCLUSION: The present study strongly suggests that the pathology of
      vestibular neuritis is in the superior vestibular nerve branch. Also it can be
      speculated that at the early stage of this disease, the pathology is in the whole
      branch of the nerve. Subsequently, the anterior canal branch recovers faster than
      the horizontal canal branch.

PMID- 19577390
TI  - Toxoplasmosis among pregnant women in France: risk factors and change of
      prevalence between 1995 and 2003.
AB  - BACKGROUND: Congenital toxoplasmosis may affect any organ, produce severe
      complications such as hydrocephalus and lead to ocular lesions which can appear
      late after birth. Fetal outcome can be fatal. During pregnancy, the mother can
      become infected, particularly by eating undercooked meat or poorly washed raw
      fruits and vegetables. In France, prevention of congenital toxoplasmosis is based
      on serial serology tests, performed repeatedly until delivery for pregnant women
      who remain negative then at the first prenatal visit. METHODS: We used
      toxoplasmosis serology data collected during national perinatal surveys conducted
      in 1995 and 2003 to estimate toxoplasmosis prevalence, assess risk factors and
      ascertain time trends in prevalence. In each survey, socioeconomic variables as
      well as the serological status for toxoplasmosis were collected for all pregnant
      women who had terminated a pregnancy during a given week period. RESULTS: In
      2003, 15,108 pregnant women were included; the prevalence of Toxoplasma infection
      was 43.8% (95% CI: 43.0-44.6). Prevalence increased with age and was greater for
      those who lived in the Southwest of France, the greater Paris area and in
      overseas districts. In 2003, as in 1995, prevalence increased with education
      level, occupational status of the household and number of pregnancies. Prevalence
      decreased 19% between 1995 and 2003. The decrease was significantly greater for
      pregnant women aged less than 30 years than for those aged more or equal to 30
      years. CONCLUSION: Although it decreased over time, toxoplasmosis prevalence
      remained higher in France than in other European countries. With more than one
      out of two women in France susceptible of having Toxoplasma infection, it is
      important to promote preventive measures to avoid infection during pregnancy.

PMID- 19577391
TI  - [The tree hiding the forest].

PMID- 19577392
TI  - [Haemochromatoses. New understanding, new treatments].
AB  - Haemochromatoses encompass a variety of genetic iron overload diseases. The most
      frequent entity remains HFE-related haemochromatosis. The other syndromes include
      diseases related to mutations of the hemojuvelin, hepcidin, transferrin receptor
      2 and ferroportin genes. Iron excess is due to deficiencies in either hepcidin or
      ferroportin, the two key regulatory proteins of iron metabolism. Diagnosis rests
      essentially upon non invasive clinical, biological and imaging criteria. The
      mainstay of iron overload treatment is venesection therapy in case of hepcidin
      deficiency, the therapeutic approach for the future being hepcidin
      supplementation. In ferroportin deficiency, oral chelation is an interesting
      orientation. The recent creation in France of a reference center and of several
      competence centers for rare genetic iron overload diseases represents a valuable
      organization for improving both the understanding of the diseases and the
      management of the patients.

PMID- 19577393
TI  - Dose and perceived image quality in chest radiography.
AB  - Chest radiography is the most commonly performed diagnostic X-ray examination.
      The radiation dose to the patient for this examination is relatively low but
      because of its frequent use, the contribution to the collective dose is
      considerable. Consequently, optimization of dose and image quality offers a
      challenging area of research. In this article studies on dose reduction,
      different detector technologies, optimization of image acquisition and new
      technical developments in image acquisition and post processing will be reviewed.
      Studies indicate that dose reduction in PA chest images to at least 50% of
      commonly applied dose levels does not affect diagnosis in the lung fields;
      however, dose reduction in the mediastinum, upper abdomen and retrocardiac areas
      appears to directly deteriorate diagnosis. In addition to patient dose, also the
      design of the various digital detectors seems to have an effect on image quality.
      With respect to image acquisition, studies showed that using a lower tube voltage
      improves visibility of anatomical structures and lesions in digital chest
      radiographs but also increases the disturbing appearance of ribs. New techniques
      that are currently being evaluated are dual energy, tomosynthesis, temporal
      subtraction and rib suppression. These technologies may improve diagnostic chest
      X-ray further. They may for example reduce the negative influence of over
      projection of ribs, referred to as anatomic noise. In chest X-ray this type of
      noise may be the dominating factor in the detection of nodules. In conclusion,
      optimization and new developments will enlarge the value of chest X-ray as a
      mainstay in the diagnosis of chest diseases.

PMID- 19577395
TI  - Dependence of the fractional anisotropy in cervical spine from the number of
      diffusion gradients, repeated acquisition and voxel size.
AB  - The aim of this study is to investigate the consequences of using different
      gradient schemes, number of repeated measurements and voxel size on the
      fractional anisotropy (FA) value in a diffusion tensor imaging (DTI) sequence on
      the cervical tract of the spinal cord. Twenty healthy volunteers underwent a
      total of 86 DTI axial acquisitions performed by using different voxel size and
      number of diffusion gradient directions (NDGDs). Three different diffusion
      gradient schemes were applied, named 6, 15 and 32 according to the NDGD.
      Furthermore, some acquisitions were repeated to investigate the effects of image
      averaging on FA value. Our results indicate that the FA value in the cervical
      spinal cord decreases when increasing the NDGD for a fixed spatial resolution, or
      when identical acquisitions are repeated, thus, increasing the acquisition time.
      This effect is observed in all subjects without exceptions, and the differences
      result statistically significant: the average FA obtained from 6, 15 and 32 NDGD
      is 0.84 (range, 0.82-0.87), 0.75 (range, 0.68-0.80) and 0.70 (range, 0.65-0.77),
      respectively, for isotropic 8 mm(3) voxel size. When varying the spatial
      resolution in a volume range of 2 to 8 mm(3) for a fixed NDGD (6 or 15), the
      differences in FA values are smaller albeit still statistically significant: the
      smaller the voxel, the larger the FA. No significant dependence of the FA value
      from the spatial resolution is observed in the 32 NDGD acquisitions in the
      studied volume range. In conclusion, our results indicate that the value of the
      FA in the cervical tract of the spinal cord vary with regularity in intrasubject
      acquisitions when modifying the NDGD and when repeated acquisitions are used;
      these observations confirm that the signal-to-noise ratio introduces a systematic
      error in FA measurements that does not allow simple comparison of quantitative
      results obtained from separated studies.

PMID- 19577394
TI  - Treatment strategies in surgery for rheumatoid arthritis.
AB  - Rheumatoid arthritis due to the chronic inflammation of the synovial joints leads
      to permanent articular cartilage and bone damage. Subsequent instability and
      mutilation of the joint might happen, and the resulting joint pain and stiffness
      cause impaired function. The degree of damage is traditionally assessed by
      radiograph and represents a clinical tool for the evaluation of both disease
      progression and the effectiveness of interventional therapy. The classification
      of destruction is therefore done with radiograph and the assessment of the
      clinical picture. Depending on the radiologic stage different therapy concepts,
      ranging from conservative to operative, are established. It is the goal of
      surgery to restore motion and function in a painless joint. Surgery can be done
      to prevent the joint from further destruction or to replace the joint after
      resection. Different concepts based on radiologic findings are presented in this
      review.

PMID- 19577396
TI  - Elliptical magnetic resonance spectroscopic imaging with GRAPPA for imaging brain
      tumors at 3 T.
AB  - Magnetic Resonance Spectroscopic Imaging (MRSI) is a technique for imaging
      spatial variation of metabolites and has been very useful in characterizing
      biochemical changes associated with disease as well as response to therapy in
      malignant pathologies. This work presents a self-calibrated undersampling to
      accelerate 3D elliptical MRSI and an extrapolation-reconstruction algorithm based
      on the GRAPPA method. The accelerated MRSI technique was tested in three
      volunteers and five brain tumor patients. Acceleration allowed larger spatial
      coverage and consequently, less lipid contamination in spectra, compared to fully
      sampled acquisition within the same scantime. Metabolite concentrations measured
      from the accelerated acquisitions were in good agreement with measurements
      obtained from fully sampled MRSI scans.

PMID- 19577397
TI  - Quantitative assessment of regional systolic and diastolic functions and temporal
      heterogeneity of myocardial contraction in patients with myocardial infarction
      using cine magnetic resonance imaging and Fourier fitting.
AB  - PURPOSE: The objective of this study is to determine regional left ventricle (LV)
      function and temporal heterogeneity of LV wall contraction by analyzing regional
      time-volume curve (TVC) after Fourier fitting and to assess altered systolic and
      diastolic functions and temporal indices of myocardial contraction in infarcted
      segments in comparison with noninfarcted myocardium in patients with myocardial
      infarction (MI). METHODS: Steady-state cine magnetic resonance (MR) and late
      gadolinium-enhanced (LGE) MR images were acquired using a 1.5-T MR system in 60
      patients with MI. Regional LV function was determined by analyzing regional TVC
      in 16 segments. The fitted regional TVC was generated by Fourier curve fitting
      with five harmonics. Regional LV ejection fraction (EF), peak ejection rate
      (PER), peak filling rate (PFR), time to end-systole and time to peak filling
      (TPF) were determined from TVC and the first derivative curve. RESULTS: On LGE MR
      imaging (MRI), MI was observed in 307 of 960 segments (32.0%). Regional EF and
      PER averaged in LGE segments were 49.3+/-14.5% and 2.83+/-0.65 end-diastolic
      volume (EDV)/s, significantly lower than those in normal segments (66.7+/-11.9%
      and 3.63+/-0.60 EDV/s, P<.001 and P<.01, respectively). In addition, regional
      PFR, an index of diastolic function, was significantly reduced in LGE segments
      (1.94+/-0.54 vs. 2.86+/-0.68 EDV/s, P<.01). Time to end-systole and TPF were
      significantly greater in LGE segments (380.2+/-57.6 and 169.3+/-45.4 ms) than in
      normal segments (300.9+/-55.1 and 132.3+/-43.0 ms, P<.01 and P<.01,
      respectively). CONCLUSIONS: Analysis of regional TVC on cine MRI after Fourier
      fitting allows quantitative assessment of regional systolic and diastolic LV
      functions and temporal heterogeneity of LV wall contraction in patients with MI.

PMID- 19577398
TI  - Brain networks responsive to aversive visual stimuli in humans.
AB  - The neural mechanisms subserving recognition of noxious stimuli and empathy for
      pain appear to involve at least in part the cortical regions associated with the
      processing of pain affect. An important issue concerns the specificity of brain
      networks associated with observing and representing painful conditions, in
      comparison with other unpleasant stimuli. Recently, we found both similarities
      and differences between the brain patterns of activity related to the observation
      of noxious or disgusting stimuli delivered to one hand or foot. Overlap regions
      included the perigenual anterior cingulate (pACC), whose activity was related to
      the perceived unpleasantness. We aimed here at revealing how pACC functional
      connectivity changes in relationship to the different experimental conditions,
      using a psychophysiological interaction model. Activity in pACC during the
      observation of painful stimuli was specifically and positively related to regions
      in the right hemisphere, including portions of the prefrontal, midcingulate and
      insular cortex. On the other hand, positive changes in pACC connectivity during
      the vision of disgusting stimuli were present in the right basal ganglia. These
      data suggest that pACC activity is part of different networks involved in the
      recognition of painful or disgusting stimuli.

PMID- 19577399
TI  - Enhancement of abdominal organs on hepatic arterial phase: quantitative
      comparison between 1.5- and 3.0-T magnetic resonance imaging.
AB  - PURPOSE: To compare the extent of enhancement of abdominal organs as shown on
      subphases of hepatic arterial phase quantitatively between 1.5- and 3.0-T MRI
      among patients with various abdominal conditions. MATERIALS AND METHODS: A total
      of 126 patients, of whom 68 were women (age range, 3-82 years; mean age, 48
      years) and 58 were men (age range, 6-73 years; mean age, 50 years), were included
      in the study. Of 126 patients, 98 were scanned at 1.5 T and 28 were scanned at
      3.0 T. The presence of one of three predefined subphases of hepatic arterial
      phase was determined on early post-gadolinium sequence in each patient by two
      reviewers in consensus. Extent of enhancement of the kidney, pancreas, spleen and
      liver on these subphases was determined quantitatively by measuring the signal
      intensities. Mann Whitney-Wilcoxon test was used to compare the contrast
      enhancement of organs on each subphase between 1.5- and 3.0-T MRI. RESULTS: The
      kidney, spleen, pancreas and liver demonstrated 1.79- to 2.45-, 1.65- to 1.97-,
      1.66- to 1.8- and 1.1- to 2.02-fold higher enhancement on the subphases of
      hepatic arterial phase at 3.0 T compared to 1.5 T, respectively. The differences
      in contrast enhancement were significant for the kidney, pancreas and spleen on
      all subphases between 1.5 and 3.0 T. CONCLUSION: The relative enhancement of the
      kidney, spleen and pancreas is consistently and significantly higher at 3.0 T
      than at 1.5 T in matched subphases of hepatic arterial enhancement.

PMID- 19577400
TI  - Evaluation of intracranial stenoses and aneurysms with accelerated 4D flow.
AB  - The aim of this study was to evaluate intracranial arterial stenoses and
      aneurysms with accelerated time-resolved three-dimensional (3D) phase-contrast
      MRI or 4D flow. The 4D flow technique was utilized to image four normal
      volunteers, two patients with intracranial stenoses and two patients with
      intracranial aneurysms. In order to reduce scan time, parallel imaging was
      combined with an acquisition strategy that eliminates the corners of k-space. In
      the two patients with intracranial stenoses, 4D flow velocity measurements showed
      that one patient had normal velocity profiles in agreement with a previous
      magnetic resonance angiogram (MRA), while the second showed increased velocities
      that indicated a less significant narrowing than suspected on a previous MRA, as
      confirmed by catheter angiography. This result may have prevented an invasive
      angiogram. In the two patients with 4-mm intracranial aneurysm, one had a stable
      helical flow pattern with a large jet, while the other had a temporally unstable
      flow pattern with a more focal jet possibly indicating that the second aneurysm
      may have a higher likelihood of rupture. Accelerated 4D flow provides time
      resolved 3D velocity data in an 8- to 10-min scan. In the stenosis patients, the
      addition of 4D flow to a traditional MRA adds the velocity data provided from
      transcranial Doppler ultrasound (TCD) possibly allowing for more accurate grading
      of stenoses. In the aneurysm patients, visualization of flow patterns may help to
      provide prognostic information about future risk of rupture.

PMID- 19577401
TI  - Single-sided mobile NMR apparatus using the transverse flux of a single permanent
      magnet.
AB  - This study presents a simple design for a mobile, single-sided nuclear magnetic
      resonance (NMR) apparatus which uses the magnetic flux parallel to the
      magnetization direction of a single, disc-shaped permanent magnet polarized in
      radial direction. The stray magnetic field above the magnet is approximately
      parallel to the magnetization direction of the magnet and is utilized as the B(0)
      magnetic field of the apparatus. The apparatus weighs 1.8 kg, has a compact
      structure and can be held in one's palm. The apparatus generates a B(0) field
      strength of about 0.279 T at the center of apparatus surface and can acquire a
      clear Hahn echo signal of a pencil eraser block lying on the RF coil in one shot.
      Moreover, a strong static magnetic field gradient exists in the direction
      perpendicular to the apparatus surface. The strength of the static magnetic field
      gradient near the center of the apparatus surface is about 10.2 T/m; one
      dimensional imaging of thin objects and liquid self-diffusion coefficient
      measurements can be performed therein. The available spatial resolution of the
      one-dimensional imaging experiments using a 5 x 5 mm horizontal sample area is
      about 200 mum. Several nondestructive inspection applications of the apparatus,
      including distinguishing between polyethylene grains of different densities,
      characterizing epoxy putties of distinct set times and evaluating the fat content
      percentages of milk powders, are also demonstrated. Compared with many previously
      published designs, the proposed design bears a simple structure and generates a
      B(0) magnetic field parallel to the apparatus surface, simplifying apparatus
      construction and simultaneously rendering the selection of the radiofrequency
      coil relatively flexible.

PMID- 19577403
TI  - Identification of gentamicin impurities by liquid chromatography tandem mass
      spectrometry.
AB  - An HPLC/MS/MS method was developed for identification of impurities in
      gentamicin. The HPLC was performed on a Synergy Hydro-RP column using 50 mM
      trifluoroacetic acid (TFA), pH 2 adjusted with ammonium solution and methanol as
      mobile phase. All impurities in gentamicin were separated from main gentamicin
      components. Atmospheric pressure chemical ionization (APCI) was used and product
      mass spectra of protonated molecules were acquired. Seventeen impurities were
      detected in gentamicin. Reference compounds: gentamicins: C2b, B, B1, G-418,
      sisomicin, garamine and gentamines: C1, C1a, C2, C2a were used for spectra
      interpretation and impurities identification. All MS/MS spectra were interpreted
      and fragmentation transitions for gentamicins and in general for aminoglycoside
      antibiotics (AG) were proposed. All impurities were identified. More than one
      isomere were proposed for three impurities.

PMID- 19577402
TI  - Blood oxygen level-dependent and perfusion magnetic resonance imaging: detecting
      differences in oxygen bioavailability and blood flow in transplanted kidneys.
AB  - Functional magnetic resonance imaging (fMRI) is a powerful tool for examining
      kidney function, including organ blood flow and oxygen bioavailability. We have
      used contrast enhanced perfusion and blood oxygen level-dependent (BOLD) MRI to
      assess kidney transplants with normal function, acute tubular necrosis (ATN) and
      acute rejection. BOLD and MR-perfusion imaging were performed on 17 subjects with
      recently transplanted kidneys. There was a significant difference between
      medullary R2 values in the group with acute rejection (R2=16.2/s) compared to
      allografts with ATN (R2=19.8/s; P=.047) and normal-functioning allografts
      (R2=24.3/s;P=.0003). There was a significant difference between medullary
      perfusion measurements in the group with acute rejection (124.4+/-41.1 ml/100 g
      per minute) compared to those in patients with ATN (246.9+/-123.5 ml/100 g per
      minute; P=.02) and normal-functioning allografts (220.8+/-95.8 ml/100 g per
      minute; P=.02). This study highlights the utility of combining perfusion and BOLD
      MRI to assess renal function. We have demonstrated a decrease in medullary R2
      (decrease deoxyhemoglobin) on BOLD MRI and a decrease in medullary blood flow by
      MR perfusion imaging in those allografts with acute rejection, which indicates an
      increase in medullary oxygen bioavailability in allografts with rejection,
      despite a decrease in blood flow.

PMID- 19577404
TI  - Quantification of CKD-501, lobeglitazone, in rat plasma using a liquid
      chromatography/tandem mass spectrometry method and its applications to
      pharmacokinetic studies.
AB  - CKD-501 (i.e., lobeglitazone), a potent agonist for both PPARalpha/gamma, is a
      new drug that has potential clinical applications in the management of type-2
      diabetes. The objective of this study was to develop a rapid and sensitive method
      for the determination of CKD-501 in rat plasma and to assess the applicability of
      the assay to pharmacokinetic studies. Rat plasma samples were processed using a
      fast flow protein precipitation (FF-PPT) method and then introduced onto an LC
      MS/MS system for quantification. The analyte and rosiglitazone, an internal
      standard, were analyzed by multiple reactions monitoring (MRM) at m/z transitions
      of 482.0-->258.0 for CKD-501 and 358.0-->135.0 for the internal standard. The
      lower limit of quantification (LLOQ) was determined at 50 ng/mL, with an
      acceptable linearity in the range from 50 to 10,000 ng/mL (R>0.999). Validation
      parameters such as accuracy, precision, dilution, recovery, matrix effect and
      stability were found to be within the acceptance criteria of the assay validation
      guidelines, indicating that the assay is applicable to estimating the
      concentration in the range studied. The concentration of CKD-501 was readily
      quantifiable in plasma samples up to 24 h post-dose in rats that had received an
      oral dose of 1 mg/kg. These observations suggest, therefore, that the validated
      assay can be used in pharmacokinetic studies of CKD-501 in small animals such as
      the rat.

PMID- 19577405
TI  - Incentives for retention of pregnant substance users: a secondary analysis.
AB  - Retention of pregnant substance users in treatment is challenging. In a multisite
      clinical trial, 200 pregnant substance users entering outpatient treatment at one
      of four programs were randomized to either three individual sessions of
      Motivational Enhancement Therapy for Pregnant Substance users or three individual
      sessions normally provided. Retail scrip from $25 to $30 was provided for
      attendance of research visits but not treatment visits. A post hoc analysis of
      the non-methadone-maintained participants (n = 175) evaluated the hypotheses that
      monetary reinforcement for attendance would result in more consecutive, and
      overall, weeks of attendance of research versus nonincentivized treatment visits.
      Findings indicate participants were nearly three times as likely to attend 4
      consecutive weeks of research visits versus treatment sessions. There was no
      effect for income while fewer dependents were associated with more consecutive
      weeks of attendance. Incentives in the $25-to-$30 range may serve to
      significantly increase attendance and retention.

PMID- 19577407
TI  - [Acute traumatic haemorrhagic shock and transfusion: the French army policy].

PMID- 19577406
TI  - Buprenorphine adoption in the National Drug Abuse Treatment Clinical Trials
      Network.
AB  - The National Drug Abuse Treatment Clinical Trials Network (CTN), a collaborative
      federal research initiative that brings together universities and community-based
      treatment programs (CTPs), has conducted multiple clinical trials of
      buprenorphine for opioid dependence. Part of the CTN's mission is to promote the
      adoption of evidence-based treatment technologies. Drawing on a data collected
      during face-to-face interviews with administrators from a panel of 206 CTPs, this
      research examines the adoption of buprenorphine over a 2-year period. These data
      indicated that the adoption of buprenorphine doubled between the baseline and 24
      month follow-up interviews. Involvement in a buprenorphine protocol continued to
      be a strong predictor of adoption at the 2-year follow-up, although adoption of
      buprenorphine tripled among those CTPs without buprenorphine-specific protocol
      experience. For-profit CTPs and those offering inpatient detoxification services
      were more likely to adopt buprenorphine over time. A small percentage of programs
      discontinued using buprenorphine. These findings point to the dynamic nature of
      service delivery in community-based addiction treatment and the continued need
      for longitudinal studies of organizational change.

PMID- 19577408
TI  - [Hyaluronidase: Here we go again].
AB  - OBJECTIVE: To summarize the benefits and lateral effects of hyaluronidase (H) use
      in ophthalmologic anaesthesia and to address its unavailability in current
      practice in France. DATA SOURCES: The Medline data bank and the Cochrane database
      were consulted. The keywords employed separately or in combination were: H,
      regional anaesthesia, ophthalmologic surgery, local aneasthetics myotoxicity,
      diplopia. STUDY SELECTION: Original articles since 1949 were selected. We also
      selected isolated clinical cases according to their relevance compared with the
      existing literature. DATA SYNTHESIS: H is a "spreading factor" of animal origin
      used as an adjuvant in ophthalmic anaesthesia for more than half a century. It
      allows a moderate better block quality with a slightly quicker onset. It also
      limits the acute intraocular pressure increase secondary to periocular injection
      and seems to have a protective effect against local anaesthetics myotoxicity
      resulting in postoperative strabismus. However, during these last 50 years,
      numerous studies often ended in divergent results. CONCLUSION: H seems to be a
      useful adjuvant in ophthalmologic anaesthesia in spite of his current
      unavailability in France. Recombinant H could be the solution in the near future.

PMID- 19577409
TI  - BIS response to tamponade and dobutamine in swine varies with hypnotic/opiate
      ratio.
AB  - OBJECTIVES: This study in swine assessed BIS stability in response to decreases
      and increases in cardiac output under two propofol/remifentanil dosage
      combinations, both producing the same depth of surgical anaesthesia. METHODS:
      Eight anaesthetized-paralyzed ventilated adult swine were studied using a random
      order cross-over design. Four received a P low/R high combination (P, 8.4+/-0.9
      mg/kg/h; and R, 0.54+/-0.02 microg/kg/min) and then a P high/R low combination
      (P, 26.7+/-2.1mg/kg/h; and R, 0.34+/-0.01 microg/kg/min). The other four had
      these two combinations in the reverse order. Under each P/R combination, and
      after a 60-minutes steady state, a 15-minute stable cardiac tamponade was induced
      by intrapericardial gelatine infusion. Then, after returning to pre tamponade
      condition, a 15 minutes period with dobutamine was allowed. RESULTS: Tamponade
      induced falls in average mean arterial pressure (MAP) (from 79+/-18 to 47+/-9 mm
      Hg; p<0.05) and cardiac output (Qc) (from 1.90+/-0.46 l/min to 1.20+/-0.38 l/min,
      p<0.05). Conversely, dobutamine increased both MAP and Qc (p<0.05). During each
      type of hemodynamic challenges, changes in anaesthesia depth as assessed by BIS
      differed dramatically between the two drug combinations, despite observing the
      same percent change in P and R effect-site concentration. With P high/R low and
      tamponade, BIS fell from 65+/-5 to 29+/-10 (p<0.05); dobutamine produced opposite
      effects. With P low/R high, in contrast, BIS was not influenced by either of the
      hemodynamic challenges. CONCLUSION: Conversely to a high propofol/low
      remifentanil combination, a low propofol/high remifentanil combination allows
      constant anaesthetic depth in the face of haemodynamic challenges.

PMID- 19577410
TI  - [Hypokaliemic myopathy: a rare complication of hyperemesis gravidarum].

PMID- 19577411
TI  - [Pediatric liver transplantation].
AB  - Liver transplantations (LT) performed in children aged younger than 16 years
      account for 6 to 8% of the total number of LT performed yearly in France.
      Indications for pediatric LT are mainly chronic cholestatic diseases of neonatal
      onset that lead to biliary cirrhosis; the most common is biliary atresia. Because
      most children are very young at transplantation (median age of 2 years), LT is
      performed in most cases with left lateral segments from a deceased donor or a
      related living donor. This increases the rate of postoperative vascular and
      biliary complications, compared with whole-liver transplantation. The principal
      early cause of death is sepsis. Some specific post-LT complications occur more
      frequently in young children than adolescents or adults: EBV-related post
      transplantation lymphoproliferative disease and food allergies in young
      recipients treated with tacrolimus and acquired renal cystic disease, associated
      with renal dysfunction, mostly in children treated with cyclosporine. Despite the
      high rate of early post-LT complications, 10-year survival exceeds 70 to 80% and
      health-related quality of life is close to normal. Only about 10% of children
      will require a late retransplantation, mainly for chronic liver graft rejection,
      which most often results from poor or non-adherence to immunosuppressants,
      especially during adolescence.

PMID- 19577412
TI  - Delirium recognition and sedation practices in critically ill patients: a survey
      on the attitudes of 1015 Brazilian critical care physicians.
AB  - PURPOSE: The aim of the study was to characterize the practices of Brazilian ICU
      physicians toward sedation and delirium. MATERIALS AND METHODS: A cross-sectional
      survey was conducted among a convenience sample of critical care physicians
      between April and June 2008. RESULTS: One thousand fifteen critical care
      physicians responded. Sedation scoring systems were used by 893 (88.3%) of the
      respondents. The Ramsay and Richmond Agitation-Sedation Scale were used by 81.9%
      and 6.8% of the respondents, respectively. Most respondents did not discuss
      sedation targets (62.8%) or practice daily sedative interruption (68.3%) in most
      patients. More than half of the respondents (52.7%) used a sedation protocol, and
      the most used sedatives were midazolam (97.8%), fentanyl (91.5%), and propofol
      (55%). A significant rate of the respondents (42.7%) estimated that more than 25%
      of patients under mechanical ventilation have delirium, but 53.5% occasionally
      assessed patients for delirium. Thirteen percent used specific delirium scales,
      with the Confusion Assessment Method for intensive care unit (ICU) being the most
      applied. Delirium was often treated with haloperidol (88.1%); however, atypical
      antipsychotics (36.3%) and benzodiazepines (42.3%) were also used. CONCLUSIONS:
      Despite the recent advances in knowledge of sedation and delirium, most of them
      are still not translated into clinical practice. Significant variation in
      practice is observed among ICU physicians and represents a potential target for
      future research and educational interventions.

PMID- 19577413
TI  - Factors associated with anemia in patients with cancer admitted to an intensive
      care unit.
AB  - PURPOSE: The study aimed to evaluate the relative impact of clinical and
      demographic factors associated with the prevalence and incidence of anemia
      (hemoglobin [Hb] <12 g/dL) in critically ill patients with cancer. MATERIALS AND
      METHODS: We performed an electronic chart review for demographic and clinical
      data of adult patients with cancer with or without anemia admitted to the
      intensive care unit (ICU). Prevalence of anemia was determined at admission, and
      incidence determined if anemia developed during ICU stay. Anemia was classified
      as mild, moderate, or severe. The additive impact of clinical and demographic
      factors was evaluated by using a hierarchical linear regression model. RESULTS: A
      total of 4705 patients were included in the study. The prevalence and incidence
      of anemia were 68.0% and 46.6%, respectively. In prevalent cases, we found that
      the clinical covariates modified sequential organ failure assessment score,
      admission to the medical ICU, prior chemotherapy, diagnosis of hematologic
      cancer, and length of hospital stay before ICU admission explained 18.7% of the
      variance in the model, whereas the demographic covariates (age, sex, and race)
      explained only an additional 0.6%. The pattern was similar for incidence cases.
      CONCLUSIONS: Clinical factors are more influential than demographic factors in
      the observed rates of prevalence and incidence of anemia in the ICU; thus,
      protocols are needed to identify subgroups of patients with cancer who could
      benefit from novel management strategies.

PMID- 19577414
TI  - Critical care medicine and medical simulation: 6000 years, and counting, of
      lessons from the game of chess.

PMID- 19577416
TI  - Invited Commentary for: Predicting clinical physiology: a Markov chain model of
      heart rate recovery after spontaneous breathing trials in mechanically ventilated
      patients.

PMID- 19577415
TI  - Reliability of intensive care unit admitting and comorbid diagnoses, race,
      elements of Acute Physiology and Chronic Health Evaluation II score, and
      predicted probability of mortality in an electronic intensive care unit database.
AB  - BACKGROUND: Although reliability of severity of illness and predicted probability
      of hospital mortality have been assessed, interrater reliability of the
      abstraction of primary and other intensive care unit (ICU) admitting diagnoses
      and underlying comorbidities has not been studied. METHODS: Patient data from one
      ICU were originally abstracted and entered into an electronic database by an ICU
      nurse. A research assistant reabstracted patient demographics, ICU admitting
      diagnoses and underlying comorbidities, and elements of Acute Physiology and
      Chronic Health Evaluation II (APACHE II) score from 100 random patients of 474
      admitted during 2005 using an identical electronic database. Chamberlain's
      percent positive agreement was used to compare diagnoses and comorbidities
      between the 2 data abstractors. A kappa statistic was calculated for demographic
      variables, Glasgow Coma Score, APACHE II chronic health points, and HIV status.
      Intraclass correlation was calculated for acute physiology points and predicted
      probability of hospital mortality. RESULTS: Percent positive agreement for ICU
      primary and other admitting diagnoses ranged from 0% (primary brain injury) to
      71% (sepsis), and for underlying comorbidities, from 40% (coronary artery bypass
      graft) to 100% (HIV). Agreement as measured by kappa statistic was strong for
      race (0.81) and age points (0.95), moderate for chronic health points (0.50) and
      HIV (0.66), and poor for Glasgow Coma Score (0.36). Intraclass correlation showed
      a moderate-high agreement for acute physiology points (0.88) and predicted
      probability of hospital mortality (0.71). CONCLUSION: Reliability for ICU
      diagnoses and elements of the APACHE II score is related to the objectivity of
      primary data in the medical charts.

PMID- 19577417
TI  - Noninvasive ventilation in patients with malignancies and hypoxemic acute
      respiratory failure: a still pending question.

PMID- 19577418
TI  - Accuracy of clinical diagnosis and decision to commence intravenous prostaglandin
      E1 in neonates presenting with hypoxemia in a transport setting.
AB  - BACKGROUND: Setting goals for monitoring and initiating life-saving interventions
      such as prostaglandins (prostaglandin E(1) [PGE(1)]) during transport
      stabilization are dependent on establishing an accurate clinical diagnosis.
      OBJECTIVE: The aim of this study was to determine the accuracy of clinical
      diagnosis of suspected congenital heart disease (CHD) and the decision to
      initiate PGE(1) in neonates presenting with hypoxemia. METHODS: A retrospective
      cohort study (2002-2004) on hypoxemic neonates who were transported to an outborn
      neonatal intensive care unit (NICU) was conducted. Provisional diagnosis
      established by the transport team was categorized as suspected CHD (group 1),
      suspected persistent pulmonary hypertension of the newborn (group 2), and
      suspected CHD and/or persistent pulmonary hypertension of the newborn (group 3)
      based on history, physical examination, laboratory test, chest radiograph, and
      initial response to treatment. A definitive diagnosis was established on arrival
      to NICU by echocardiography. RESULTS: A total of 115 neonates were included in
      the study. The mean gestational age at birth, median age at admission to NICU,
      and the mean stabilization time were 38.2 (2.4) weeks, 1 (1-26) days, and 217
      (108) hours, respectively. The interventions provided during transport
      stabilization included mechanical ventilation (n = 86, 75%), PGE(1) (n = 70,
      61%), inotropes (n = 41, 36%), and fluid bolus (n = 50, 43%). The accuracy of a
      provisional diagnosis of CHD by transport team was 87.7% and the positive
      predictive value was 88.1%. Sixty neonates (88%) received PGE(1) appropriately.
      Eight neonates (12%) with duct-dependent CHD (n = 68) did not receive PGE(1) and
      were considered as missed opportunities. Ventilated neonates in groups 1 and 3
      were identified as the groups that can potentially benefit from more liberal use
      of PGE(1) and without any adverse effects. CONCLUSION: Although the accuracy of a
      diagnosis of CHD and the decision to initiate PGE(1) was high, 12% of neonates
      with a duct-dependent CHD were transported without commencement of PGE(1). Lower
      thresholds for PGE(1) administration to hypoxemic neonates may potentially
      improve preoperative stabilization and minimize neonatal morbidity.

PMID- 19577419
TI  - Drotrecogin alfa (activated) for severe sepsis: could we consider a shorter
      treatment period in patients with a favorable course?
AB  - PURPOSE: The objective of this study was to develop a model to identify patients
      in whom drotrecogin alfa (activated) (DAA) might be administered for periods
      shorter than the recommended 96 hours. METHODS: We did a retrospective chart
      review of all 124 patients treated with a standard 96-hour infusion of DAA in a
      31-bed department of intensive care. Using a stepwise approach, we identified and
      combined parameters that could help predict outcomes to achieve the best
      sensitivity associated with 100% specificity. RESULTS: Twenty-one (17%) of the
      124 patients had a favorable outcome (left the intensive care unit within 5 days
      of DAA initiation); of these, 11 had an increase in arterial pH in the first 24
      hours of treatment compared with 22 (21%) of the 103 patients with intermediate
      (intensive care unit stay >5 days after DAA initiation) or unfavorable (died
      within 5 days of DAA initiation) outcomes (P = not significant). Eight (72.7%) of
      these 11 patients and no other patient showed a decrease in sequential organ
      failure assessment score of at least 50% during the first 24 hours (P < .001). By
      combining these 2 variables, we could identify, with 100% specificity, 8 of the
      patients with a favorable outcome (38%) who made a prompt recovery. CONCLUSIONS:
      A simple model based on sequential organ failure assessment score and arterial pH
      can help identify patients with a rapid favorable course in whom a shorter
      duration of DAA treatment may be justified.

PMID- 19577420
TI  - Bilateral measurement of bispectral index and mid-latency auditory evoked
      potentials in patients with unilateral brain lesions.

PMID- 19577421
TI  - The brief fatigue inventory: comparison of data collection using a novel audio
      device with conventional paper questionnaire.
AB  - An Electronic Portable Information Collection audio device (EPIC-Vox) has been
      developed to deliver questionnaires in spoken word format via headphones.
      Patients respond by pressing buttons on the device. The aims of this study were
      to determine limits of agreement between, and test-retest reliability of audio
      (A) and paper (P) versions of the Brief Fatigue Inventory (BFI). Two hundred
      sixty outpatients (204 male, mean age 55.7 years) attending a sleep disorders
      clinic were allocated to four groups using block randomization. All completed the
      BFI twice, separated by a one-minute distracter task. Half the patients completed
      paper and audio versions, then an evaluation questionnaire. The remainder
      completed either paper or audio versions to compare test-retest reliability. BFI
      global scores were analyzed using Bland-Altman methodology. Agreement between
      categorical fatigue severity scores was determined using Cohen's kappa. The mean
      (SD) difference between paper and audio scores was -0.04 (0.48). The limits of
      agreement (mean difference+/-2SD) were -0.93 to +1.00. Test-retest reliability of
      the paper BFI showed a mean (SD) difference of 0.17 (0.32) between first and
      second presentations (limits -0.46 to +0.81). For audio, the mean (SD) difference
      was 0.17 (0.48) (limits -0.79 to +1.14). For agreement between categorical
      scores, Cohen's kappa=0.73 for P and A, 0.67 (P at test and retest) and 0.87 (A
      at test and retest). Evaluation preferences (n=128): 36.7% audio; 18.0% paper;
      and 45.3% no preference. A total of 99.2% found EPIC-Vox "easy to use." These
      data demonstrate that the English audio version of the BFI provides an acceptable
      alternative to the paper questionnaire.

PMID- 19577422
TI  - Linking pain items from two studies onto a common scale using item response
      theory.
AB  - This study examined two approaches to linking items from two pain surveys to form
      a single item bank with a common measurement scale. Secondary analysis of two
      independent surveys: Initiative on Methods, Measurement, and Pain Assessment in
      Clinical Trials Survey with Main Survey (959 chronic pain patients; 42 pain
      items) and Pain Module (n=148; 36 pain items), and Center on Outcomes, Research
      and Education Survey (400 cancer patients; 43 pain items). There were common
      items included among the three data sets. In the first approach, all items were
      calibrated to an item response theory (IRT) model simultaneously, and in the
      second approach, items were calibrated separately and then the scales were
      transformed to a common metric. The two approaches produced similar linking
      results across the two sets of pain interference items because there was
      sufficient number of common items and large enough sample size. For pain
      intensity, simultaneous calibration yielded more stable results. Separated
      calibration yielded an unsatisfactory linking result for pain intensity because
      of a single common item with small sample size. The results suggested that a
      simultaneous IRT calibration method produces the more stable item parameters
      across independent samples, and hence, should be recommended for developing
      comprehensive item banks. Patient-reported health outcome surveys are often
      limited in sample sizes and the number of items owing to the difficulty of
      recruitment and the burden to the patients. As a result, the surveys either lack
      statistical power or are limited in scope. Using IRT methodology, survey data can
      be pooled to lend strength to each other to expand the scope and to increase the
      sample sizes.

PMID- 19577423
TI  - Post-trauma symptoms following indirect exposure to the September 11th terrorist
      attacks: the predictive role of dispositional coping.
AB  - Few data prospectively address the role of coping in the development of PTSD. In
      the present study, 308 undergraduates were assessed for coping prior to the 9/11
      WTC attack and for PTSD symptomatology at one and three-months post-9/11.
      Multiple regression analyses indicated that emotion-focused coping was predictive
      of increased symptomatology at Month 1 and Month 3, whereas problem-focused and
      avoidance-focused coping were not. Specifically, analyses predicting PTSD symptom
      factors (Intrusions, Avoidance, Dysphoria, and Hyperarousal) indicated that
      greater emotion-focused coping predicted increased Dysphoria symptoms at both
      time points and, among females, increased levels of Hyperarousal symptoms at
      Month 1. The role of coping style in the development of PTSD symptomatology and
      its clinical implications are discussed.

PMID- 19577424
TI  - Effects of systematically depriving access to computer-based stimuli on choice
      responding with individuals with intellectual disabilities.
AB  - Three adults with intellectual disabilities participated to investigate the
      effects of reinforcer deprivation on choice responding. The experimenter
      identified the most preferred audio-visual (A-V) stimulus and the least preferred
      visual-only stimulus for each participant. Participants did not have access to
      the A-V stimulus for 5 min, 5 and 24h. Following deprivation, responses produced
      1-s access to either stimulus on a concurrent continuous reinforcement continuous
      reinforcement schedule. A combination multi-element/multiple-baseline-across
      participants design showed that two participants emitted fewer responses for the
      preferred A-V stimulus following 5-min deprivation relative to 5- and 24-h
      deprivation. Higher values of deprivation did not increase the proportion of
      choice responses allocated to the A-V stimulus for any participant and could be
      attributed to preference shifts during the study.

PMID- 19577427
TI  - Determinants of prescription drug use by adolescents with intellectual
      disabilities in Taiwan.
AB  - Direct family caregivers of population-based adolescents with intellectual
      disabilities in Taiwan were surveyed regarding their perceptions of the use of
      prescribed medication and its relationship with health-related behaviors, medical
      care and preventive health utilization of people with intellectual disabilities.
      Cross-sectional data on 1419 adolescents 12-17 years of age was collected from
      the 2007 National Survey on Healthy Behaviors and Preventive Health Utilizations
      of People with Intellectual Disabilities in Taiwan. Multiple logistic regression
      models were used to examine risk profiles in relation to the use of prescribed
      medication and other relevant variables: participant characteristics, health
      related behaviors, medical care and preventive health utilization. The results
      indicate that 47.1% of subjects were accompanied by other impairments, the
      morbidity prevalence was 16.5% and 23.8% of subjects were reported to have used
      prescribed medication regularly in the past 6 months. The main reasons for
      medication use were epilepsy (36.9%), psychiatric problems (24.2%) and
      gastrointestinal problems (6.3%). A large majority of caregivers reported that
      the subject's health status was excellent (15.4%), good (38%) or fair (38%), and
      only 6.5% were reported to be in bad health. Finally, data were analyzed using a
      logistic regression model to identify possible reasons for drug use. The
      following factors correlate with the regular use of prescribed medication by
      adolescents with intellectual disabilities: Down syndrome, possession of a Major
      Illness Card, a history of smoking, an additional impairment, reported health
      status, outpatient care and acceptance of other specific medical examinations.
      Our principal conclusion was that these data indicate a need for more education
      on a variety of issues, including predisposition, healthy behavior, medical care
      and preventive health utilization issues as they relate to prescribed medication
      use, and assessment of the long-term effects of drug use on people with
      intellectual disabilities.

PMID- 19577425
TI  - Psychometric evaluation of a questionnaire to measure the quality of life of
      people with profound multiple disabilities (QOL-PMD).
AB  - Because of a shortage of valid instruments to measure the QOL of people with
      profound multiple disabilities (PMD), the QOL-PMD was developed. In the present
      study, possibilities for item reduction as well as the psychometric properties of
      the questionnaire were examined. One hundred and forty-seven informants of people
      with PMD participated in the study. Fifty items were removed from the
      questionnaire on the basis of preset criteria. Internal consistency was good for
      the total questionnaire as well as for the subscales. Evidence of the construct
      validity of the questionnaire was found. Correspondence between the groups of
      informants was moderate. The results of this preliminary analysis of the
      psychometric properties of the QOL-PMD are encouraging, but further validation of
      the measure is warranted.

PMID- 19577426
TI  - Body awareness in children with mental retardation.
AB  - The body awareness of 124 toddlers with mental retardation and of 124 children
      developing normally matched to them on age and gender was examined. Twenty-nine
      of the children with mental retardation were diagnosed as Down syndrome (DS). The
      'Pointing and Naming' Test of Berges and Lezine [Berges, J., & Lezine, I. (1978).
      Test d'imitation de gestes [Imitation test of gestures] (2nd ed.). Paris: Masson]
      was used to measure vocabulary skills on body parts. Results indicated that (a)
      the test used is reliable in terms of internal consistency; (b) children
      developing normally performed better than children with mental retardation on
      this test; (c) there were no significant differences in performance on this test
      between genders for the whole group; (d) children with DS performed as well as
      children with mental retardation of unknown origin on receptive vocabulary. On
      expressive vocabulary, they performed worse.

PMID- 19577428
TI  - Dietary folate and vitamin B12 intake before diagnosis decreases gastric cancer
      mortality risk among susceptible MTHFR 677TT carriers.
AB  - OBJECTIVE: To assess gastric cancer survival in relation to dietary intake of
      methyl donors and the methylenetetrahydrofolate reductase 677C>T (MTHFR 677C>T)
      polymorphism. METHODS: A prospective cohort of 257 incidental, histologically
      confirmed gastric cancer cases was assembled in January 2004 and followed until
      June 2006. Patients were recruited from the main oncology and/or gastroenterology
      units in Mexico City and were queried regarding their sociodemographic
      information, clinical history, and dietary habits 3 y before the onset of their
      symptoms. The intake of methyl donors was estimated with a food-frequency
      questionnaire and the MTHFR 677C>T polymorphisms were determined by polymerase
      chain reaction/restriction fragment length polymorphism analysis. Cox's
      multivariate regression models were used to estimate the mortality risk of
      gastric cancer. RESULTS: MTHFR 677TT carriers with low folate and vitamin B12
      intakes had the lowest survival rate in cases of gastric cancer. High intakes of
      folate and vitamin B12 before diagnosis was associated with decreased gastric
      cancer mortality risk in susceptible MTHFR 677TT carriers (mortality risk for
      folate 0.14, 95% confidence interval 0.04-0.46, P for trend=0.001; mortality risk
      for vitamin B12 0.23, 95% confidence interval 0.08-0.66, P for trend=0.008).
      CONCLUSION: Folate and related B vitamins may be used as an intervention strategy
      to improve the survival outcome of gastric cancer.

PMID- 19577429
TI  - Risk factors for overweight and obesity in French adolescents: physical activity,
      sedentary behavior and parental characteristics.
AB  - OBJECTIVE: We determined the prevalence by age and sex and associated factors of
      overweight and obesity in French adolescents. METHODS: We conducted a cross
      sectional study of 2385 adolescents aged 11-18 y (1213 boys and 1172 girls) from
      middle and high schools in the Aquitaine region (southwest France) in 2004-2005.
      Weight and height were measured, and adolescents filled in a questionnaire about
      their characteristics and those of their parents. Overweight and obesity were
      defined according to the age- and sex-specific body mass index cutoff points of
      the International Obesity Task force. RESULTS: Prevalence of overweight (obesity
      included) was greater in boys and younger children. The odds ratio (OR) for an
      adolescent being overweight increased with parents' being overweight (at least
      one parent overweight, OR 1.97, 1.48-2.62, P<0.0001), low paternal socioeconomic
      status (OR 1.78, 1.22-2.60, P<0.01) and sedentary behavior (22 h/wk, OR 1.33,
      1.02-1.74, P<0.05), and decreased with physical activity of parents (at least one
      parent active, OR 0.67, 0.51-0.89, P=0.01). CONCLUSION: Our data support the
      hypothesis that parental overweight and low socioeconomic status and adolescents'
      sedentary behavior are strong risk factors for adolescent overweight and obesity,
      and that parents active lifestyle is associated with a lower risk of overweight
      in their adolescents.

PMID- 19577430
TI  - Navigation-guided gap arthroplasty in the treatment of temporomandibular joint
      ankylosis.
AB  - Gap arthroplasty, used in the treatment of temporomandibular joint (TMJ)
      ankylosis, is challenging, requiring resecting of massive abnormal bone formation
      at the skull base with complex and distorted anatomy. This study evaluated the
      application of image-guided navigation to gap arthroplasty. Four gap
      arthroplasties were performed on patients with unilateral TMJ ankylosis under
      computer-assisted navigation guidance. After preoperative planning and 3
      dimensional simulation, the normal anatomic structures of the TMJ were created by
      superimposing and comparing the unaffected and affected sides. The amount and
      range of ankylotic bone to be resected was determined and displayed. Registration
      achieved an accurate match between the intra-operative anatomy and the CT virtual
      images. Anatomic structures and the position of surgical instruments were shown
      real time on the screen. In all cases the accuracy of the system measured by the
      computer did not exceed 1mm. No complications occurred and the mean minimal
      thickness of the skull base between middle cranial fossa and reconstructed
      glenoid fossa was 1.97 mm. Using image-guided navigation resulted in safe
      surgical excision of the bony ankylosis from the skull base. Navigation-guided
      resection of the ankylotic bone in the TMJ gap arthroplasty was a valuable and
      safe technique in this potentially complicated procedure.

PMID- 19577431
TI  - Bone grafting and insertion of dental implants followed by Le Fort advancement
      for correction of severely atrophic maxilla in young patients.
AB  - The atrophic maxilla often results in lateral, anteroposterior and vertical
      disproportion of the maxillary arches. This paper presents the case of a 40-year
      old male with a severely atrophic maxilla who underwent oral rehabilitation. He
      was treated with onlay and inlay iliac bone grafts followed by vestibuloplasty
      and dental implant placement 170 days after initial bone grafting. The dental
      implants were uncovered after 4 months of healing. The patient also underwent
      orthognathic surgery for correction of the maxillary basal bone and to improve
      implant positioning. At the 48-month follow-up there were no complications.

PMID- 19577432
TI  - A method for marking histopathological specimens of neck--technical note.
AB  - The authors present a technical note for marking the location of lymph nodes of
      the neck for histopathological examination. A more precise histopathological
      report permits more effective overall management of patients with neoplastic
      disease of the head and neck.

PMID- 19577433
TI  - Radiosurgical treatment of maxillary squamous cell carcinoma.
AB  - The authors report their experience of using the CyberKnife system (Accuray
      Incorporated, Sunnyvale, California, USA), a new radiosurgical device, as a
      treatment option for squamous cell carcinoma (SCC) of the maxillary sinus. A 66
      year-old man with SCC stage T4 was treated using the CyberKnife system.

PMID- 19577434
TI  - Unilateral thalamic lesions and generalized or lateralized spike wave discharges.
AB  - We report four adult patients who had thalamic lesions and lateralized or
      generalized spike wave discharges (SWDs). The first two patients also had
      cortical lesions. The role of the cortex and thalamus in the generation of SWDs
      is discussed. The third patient had a history of idiopathic generalized epilepsy
      (IGE) with intractable seizures. The last patient had partial seizures and
      absences. The coexistence of IGE with refractory focal epilepsy and the relation
      with thalamic lesions are discussed.

PMID- 19577435
TI  - In vitro susceptibility of Burkholderia pseudomallei to antimicrobial peptides.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically
      resistant to many antibiotics, resulting in high mortality rates of 19% in
      Australia and even 50% in Thailand. Antimicrobial peptides (AMPs) possess potent
      broad-spectrum bactericidal activities and are regarded as promising therapeutic
      alternatives in the fight against resistant microorganisms. Moreover, these
      peptides may also affect inflammation, immune activation and wound healing. In
      this study, the in vitro activities of 10 AMPs, including histatin 5 and histatin
      variants, human cathelicidin peptide LL-37 and lactoferrin peptides, against 24
      isolates of B. pseudomallei were investigated. The results showed that the
      antibacterial activities of the individual peptides depended on peptide dose and
      bacterial isolate. Among the 10 peptides tested, LL-37 exhibited the most
      effective killing activity. The smooth type A lipopolysaccharide (LPS) phenotype
      B. pseudomallei appeared to be more susceptible than those expressing the smooth
      type B LPS and the rough type LPS. Four isolates of B. pseudomallei shown to be
      resistant to ceftazidime and trimethoprim/sulfamethoxazole were also highly
      susceptible to LL-37. These data indicate that LL-37 possesses antimicrobial
      activity against all isolates independent of the LPS phenotype and is therefore a
      promising peptide to combat B. pseudomallei infections.

PMID- 19577436
TI  - Outcome of inpatient opiate detoxification treatment in immigrants as compared to
      native Germans.
AB  - BACKGROUND: Immigration is a factor with effects on the course of substance abuse
      and treatment response, however there is little consistent data regarding outcome
      of inpatient opiate detoxification treatment in immigrants as compared to native
      patients. METHODS: Patient history and the success of current detoxification
      treatment were systematically documented in a multicenter study in Germany which
      included 10 psychiatric hospitals with specialized detoxification wards. RESULTS:
      Out of 893 patients, 240 (27%) had a migration history. We further analyzed the
      three main groups (German, n=653; Turkish, n=58; Russian origin, n=103). There
      were significant differences between groups regarding sociodemographic data, drug
      history, treatment experience and success of current treatment. However,
      considering the younger age of patients with Russian origin, analysis of younger
      patients (<31 years) detected only minor group differences. In multiple logistic
      regressions age and center showed statistically significant associations with all
      outcome variables (early dropout, achievement of drug-free urine screen, regular
      completion of detoxification treatment, and referral to further treatment), while
      (Russian) origin was associated only with premature termination of treatment.
      CONCLUSION: Young men were the main problem group regardless of origin.
      Significant center effects raise doubts regarding results from monocenter
      research.

PMID- 19577437
TI  - Response to prophylactic lithium in bipolar disorder may be associated with a
      preservation of executive cognitive functions.
AB  - We assessed performance on the Wisconsin Card Sorting Test (WCST), measuring
      executive functions, in 30 patients showing different prophylactic effect of
      lithium (excellent lithium responders-ER, partial responders-PR and non
      responders-NR), and in fifty persons of their offspring (12 of ER, 26 of PR, and
      12 of NR). Age- and gender head-to-head matched population consisted of 30
      subjects for lithium group and 50 subjects for the offspring of lithium patients.
      In lithium patients, NR had significantly worse results compared to the remaining
      groups and to control subjects on perseverative errors (WCST-P) and conceptual
      responses (WCST-%conc). No differences were observed in the offspring of patients
      with different effect of lithium, however, they showed an impairment on WCST-P
      and WCST-%conc compared to matched healthy controls. Therefore, the favorable
      effect of lithium prophylaxis may be associated with a preservation of executive
      cognitive functions and the offspring of bipolar patients shows an impairment of
      such functions.

PMID- 19577438
TI  - A novel compound N(1),N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine isolated from
      Carthamus tinctorius L. and acting by serotonin transporter inhibition.
AB  - Safflower, the dry flower of Carthamus tinctorius L., has long been applied for
      empirically treating cerebral ischemia and depression in traditional Chinese
      medicine. Pathogenesis of major depression involves monoaminergic transmission.
      The present study assessed whether safflower or its isolate would be effective in
      functionally regulating monoamine transporter using in vitro screening cell
      lines. We discovered that safflower insoluble fraction significantly inhibited
      serotonin uptake in Chinese hamster ovary cells stably expressing serotonin
      transporter (i.e. S6 cells). This fraction went through an activity-guided
      isolation and an active ingredient was obtained, which was subsequently
      elucidated as a novel coumaroylspermidine analog N(1),N(5)-(Z)-N(10)-(E)-tri-p
      coumaroylspermidine using NMR techniques. Pharmacologically, this compound
      potently and selectively inhibited serotonin uptake in S6 cells or in
      synaptosomes, with IC(50) of 0.74+/-0.15 microM for S6 cells or 1.07+/-0.23
      microM for synaptosomes and with a reversible competitive property for the 5HT
      uptake inhibition. The potency of it for 5HT uptake was weaker than that of
      fluoxetine whereas efficacy generally similar for both. Animals treated with this
      testing compound showed a significant decrease in synaptosomal 5HT uptake
      capacity. Thus, N(1),N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine is a novel
      serotonin transporter inhibitor, which could improve neuropsychological disorders
      through regulating serotoninergic transmission.

PMID- 19577439
TI  - Solid state (13)C NMR analysis of human gallstones from cancer and benign gall
      bladder diseases.
AB  - Natural abundance (13)C cross polarized (CP) magic angle spinning (MAS) nuclear
      magnetic resonance (NMR) analysis of human gall bladder stones collected from
      patients suffering from malignant and benign gall bladder disease was carried out
      which revealed different polymorphs of cholesterol in these stones. All gall
      bladder stones in present study had cholesterol as their main constituent. (13)C
      CP-MAS NMR analysis revealed three forms of cholesterol molecules in these
      stones, which are anhydrous form, monohydrate crystalline with amorphous form and
      monohydrate crystalline form. Our study revealed that stones collected from
      patients associated with chronic cholecystitis (CC) disease have mostly different
      polymorph of cholesterol than stones collected from patients associated with gall
      bladder cancer (GBC). Such study will be helpful in understanding the mechanism
      of formation of gallstones which are associated with different gall bladder
      diseases. This is the first study by solid state NMR revealing different crystal
      polymorphism of cholesterol in human gallstones, extending the applicability of
      (13)C CP-MAS NMR technique for the routine study of gallstones.

PMID- 19577440
TI  - Functionalization of silver and gold nanoparticles using amino acid conjugated
      bile salts with tunable longitudinal plasmon resonance.
AB  - The vital bioactivities of bile salts are physiologically important molecules.
      The concept of using bile acids and their conjugates in nanoscience is a novel
      idea, which opens up fascinating prospects and gives way for various versatile
      properties. Here in, we report novel strategy for the synthesis of aqueous
      stable, silver and gold nanoparticles (Ag & AuNPs) using naturally occurring
      amino acid conjugated sodium salt of taurocholate (NaTC) and glycocholate (NaGC)
      as reducing and capping agents. The formation of nanoparticles was kinetically
      monitored using UV-vis spectroscopy at different time intervals. It was noticed,
      that the rate of reduction of AgNO(3) is much faster than the HAuCl(4) at fixed
      concentration of bile salts. Furthermore, the size and shape of the NPs are
      controlled and achieved by changing the nature of bile salts. The synthesized
      nanoparticles were characterized by transmission electron microscopy (TEM) and X
      ray diffraction (XRD) techniques for morphological studies. The interaction
      between nanoparticles with bile salts was investigated using FT-IR spectroscopy,
      cyclic voltammetry (CV) and thermogravimetric analysis (TGA).

PMID- 19577441
TI  - [Severe neuropsychiatric disorders in an asthmatic infant who received repeated
      glucocorticoid treatment: the importance of associated factors].
AB  - Children and adults may experience neuropsychiatric disorders during
      glucocorticoid treatment, most of which are reversible upon drug withdrawal.
      Whereas the occurrence of these disorders is well documented in teenagers, only a
      few cases have been reported in children under 3 years of age. We report on
      severe neuropsychiatric disorders that occurred in a 27-month-old child during
      glucocorticoid treatment for asthma that did not regress when treatment was
      stopped. The psychiatric symptoms suggested autism and were associated with
      deterioration of the child-mother relationship. This led the medical staff to
      initiate a dual therapy (conducted by a psychiatrist and a speech therapist)
      focused on the restoration of the maternal bond. A dramatic improvement in both
      the child's and the mother's behavior was observed within a few months. Severe
      psychiatric disorders induced by glucocorticoids can occur in young children and
      be worsened by environmental factors. The quality of the child-parent
      relationship should be kept in mind during the management of drug-induced
      psychiatric disorders.

PMID- 19577442
TI  - Chemoradiotherapy in gastrointestinal malignancies.
AB  - Over the past 30 years, significant advances have been made in the integration of
      radiation therapy and chemotherapy in the treatment of patients with localised
      gastrointestinal malignancies. The therapeutic goal of chemoradiotherapy is to
      enhance local control resulting in improved survival and outcome of these
      patients. To define the optimal sequence, agents and efficacy of these
      modalities, an array of randomised studies have been conducted in malignancies of
      the oesophagus, stomach, pancreas, colon, rectum and anus. In oesophageal cancer,
      recent studies from Germany and France indicate that patients treated with
      'definitive' chemoradiotherapy have similar survival to patients undergoing
      neoadjuvant chemoradiotherapy followed by surgery. For patients with locally
      advanced rectal cancer undergoing surgery, a phase III trial from Germany showed
      higher rates of local control with less acute and late morbidity for patients
      receiving neoadjuvant chemoradiotherapy vs adjuvant chemoradiotherapy. In
      contrast, the role of chemoradiotherapy in pancreatic cancer patients remains
      unclear and contentious. This overview highlights current results, controversies
      and potential future directions in the chemoradiotherapeutic treatment of
      selected gastrointestinal malignancies.

PMID- 19577443
TI  - Evaluation of in vivo reproductive toxicity of potassium chromate in male mice.
AB  - To evaluate the effects of potassium chromate on mice sperm cells after a short
      term exposure, male ICR-CD1 mice were administered with 5 or 10mgK(2)CrO(4)/bw
      for 4 consecutive days. One group of mice was sacrificed at day 5, starting from
      the beginning of the experiment and another group was sacrificed at day 35.
      Testis and epididymis histology was evaluated by light microscopy and testicular
      cells populations were evaluated by flow cytometry (FCM). Spermatozoa were
      collected from the epididymis and their morphology and several functional
      parameters (density, motility, viability, mitochondrial function, acrosome
      integrity) were evaluated. Furthermore, DNA fragmentation and chromatin status of
      sperm cells were assessed at both experimental periods. Besides a reduction in
      seminiferous tubules diameter, exposure to potassium chromate did not induce
      further histopathological changes in mice testis or epididymis. These results
      were supported by the analysis of testicular cellular subpopulations by FCM.
      Concerning spermatozoa morphology, an increase in the percentage of multiple
      abnormalities and a decrease in the percentage of normal spermatozoa were found
      at days 5 and 35, respectively. Although spermatozoa mitochondrial function or
      viability was not affected, its motility was significantly reduced by potassium
      chromate exposure at both experimental periods. A decrease in acrosome integrity
      was found in mice injected with 10mgK(2)CrO(4)/bw after 35 days. Exposure to
      potassium chromate did not affect either DNA fragmentation or chromatin
      susceptibility to acid denaturation of sperm cells. In this work, we were able to
      show the effects of potassium chromate on spermatozoa physiological parameters
      such as motility, morphology and acrosome status and also demonstrate that the
      doses tested did not induce DNA damage to sperm cells after one spermatogenic
      cycle.

PMID- 19577444
TI  - Isolation, characterization and biological evaluation of bioactive metabolites
      from Nocardia levis MK-VL_113.
AB  - An Actinomycete isolate found to be prominent in the laterite soils of Acharya
      Nagarjuna University (ANU) Campus, Guntur was identified as Nocardia levis MK
      VL_113 by 16S rRNA analysis. Cultural, morphological and physiological
      characteristics of the strain were recorded. Screening of secondary metabolites
      obtained from 4-day old culture broth of the strain led to the isolation of two
      fractions active against a wide variety of Gram-positive, Gram-negative bacteria
      and fungi. The structure of the first active fraction was elucidated using FT-IR,
      EI-MS, (1)H NMR and (13)C NMR spectra and identified as 1-phenylbut-3-ene-2-ol
      which is first time reported as a natural product. The compound exhibited good
      antimicrobial potential against the opportunistic and pathogenic bacteria and
      fungi. The antifungal activity of the strain and its metabolite were further
      confirmed with in vitro and in vivo studies. Evidence for the antagonism of the
      strain against Fusarium oxysporum, causing wilt disease in sorghum was
      demonstrated by the formation of inhibition zone in in vitro plate assay and
      reduction in the incidence of wilt of sorghum plants by using a green house
      trial. Analysis of the rhizosphere soil extracts by high performance liquid
      chromatography also demonstrated the production of the compound by the strain
      under in vivo conditions. As compared to the commercial fungicide mancozeb, the
      bioactive compound, 1-phenylbut-3-ene-2-ol was highly effective in controlling
      wilt of sorghum. Besides, the partially purified second fraction (PPF) subjected
      to gas chromatography-mass spectrometry revealed the presence of phenylethyl
      alcohol, dibutyl phthalate and 1,2-benzenedicarboxylic acid, 3-nitro.

PMID- 19577445
TI  - Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and
      reduces telomerase activity in the HL-60 leukemia cells.
AB  - Crude extract of Scutellaria baicalensis (S. baicalensis) has cytotoxic effect on
      human myelogenous leukemia cells (HL-60). We invesigated which compound from the
      crude extract is responsible for the cytotoxic effect on HL-60 cells. We
      identified 29 compounds from the crude extract using high performance liquid
      chromatography mass spectrometry (HPLC/MS). Two of the compounds, baicalin and
      wogonoside, are converted to baicalein and wogonin, respectively, after treatment
      with beta-glucuronidase. We observed a dose-dependent reduction in cell viability
      when cells with either wogonin or aqueous extract of S. baicalensis. Several of
      the apoptotic features including deoxyribonucleic acid (DNA) fragmentation and
      increased caspase-3 activity were found in cells treated with wogonin and aqueous
      extract. The changes were associated with down-regulation of Bcl-2, and not Bax.
      Furthermore, treatment of HL-60 cells with wogonin or S. baicalensis led to the
      inhibition of human telomerase reverse transcriptase (hTERT), human telomerase
      associated protein 1 (hTP1) and c-myc messenger ribonucleic acid (m-RNA)
      expression. Wogonin and S. baicaleisis down-regulated the telomerase activity.
      Our findings suggest that wogonin may be the major compound in S. baicalensis
      responsible for HL-60 growth inhibition in vitro. The inhibition of HL-60 cell
      growth is mediated partly through the induction of Bax/Bcl-2 apoptosis and by
      telomerase inhibition through suppression of c-myc, which is a promoter of hTERT.

PMID- 19577447
TI  - Effects of Pinus brutia bark extract and Pycnogenol in a rat model of carrageenan
      induced inflammation.
AB  - The present study was conducted to explore the anti-inflammatory activities of
      Pinus brutia bark extract and Pycnogenol in a rat model of carrageenan-induced
      inflammation. Firstly, the compositions of both samples were determined using
      HPLC. Then, carrageenan-induced paw edema was used to assess anti-inflammatory
      activity in mice. Paw volume was measured before and 1, 2, 3, 4, 5 and 6h after
      the injection of carrageenan. Intraperitoneal administration of both the extract
      and Pycnogenol inhibited paw swelling dose-dependently at 2, 3, 4, 5 and 6h after
      carrageenan injection. Both samples exhibited significant anti-inflammatory
      activities at doses of 75 and 100 mg/kg body wt. between 2 and 4 hours after
      administration (p<0.05), respectively. Additionally, P. brutia bark extract
      showed significantly better activity at doses of 75 and 100mg/kg body wt. than
      indomethacine at the dose of 10mg/kg body wt. (p<0.05). No acute toxicity was
      identified in intraplantar injection of the extract at a dose of 2000 mg/kg body
      wt.. Therefore, P. brutia bark extract possessing 3.3-fold more total catechins
      and 9.8-fold more taxifolin than Pycnogenol can be utilized as an anti
      inflammatory agent.

PMID- 19577446
TI  - Topical anti-inflammatory effect of tirucallol, a triterpene isolated from
      Euphorbia lactea latex.
AB  - Latex from Euphorbia lactea (Euphorbiaceae), a native Dominican medicinal plant,
      is claimed to be useful in the treatment of inflammation. Topical application of
      tirucallol, a tetracyclic triterpene isolated from Euphorbia lacteal latex,
      suppressed ear edema in the mouse model in a dose-dependent manner, as well as
      affecting the influx of polymorphonuclear cells in response to topical
      application of 12-O-tetradecanoylphorbol-acetate (TPA) in the mouse ear. In
      addition, the effect of tirucallol, on some macrophage functions was analyzed in
      vitro. Non-toxic concentrations of tirucallol potently inhibited nitrite
      production in lipopolysaccharide-stimulated macrophages. Western blot analysis
      showed that nitric oxide reduction was a consequence of the inhibition of
      inducible nitric oxide synthetase expression although tirucallol slightly
      affected to prostaglandin E(2) (PGE(2)) generation. The results of the study
      revealed that tirucallol (0.3%), present in Euphorbia lactea latex, exerts a
      topical anti-inflammatory effect in vivo, via a mechanism of action related to
      the neutrophil migration. On the other hand, it can be deduced that the mechanism
      of the anti-inflammatory activity of this triterpene is related to the control of
      the production of NO and its effect on the expression of iNOS.

PMID- 19577448
TI  - Effects of Devil's Claw (Harpagophytum procumbens) on the multidrug transporter
      ABCB1/P-glycoprotein.
AB  - Devil's Claw (Harpagophytum procumbens) a plant native to Southern Africa, has
      historically been used in traditional medicine to treat a wide range of diseases
      and currently is widely employed as anti-inflammatory and pain-relieving natural
      remedy in Europe and other parts of the world. AIM OF THE STUDY: Little is known
      about possible herb-drug interactions arising from effects of Devil's Claw on the
      major drug metabolizing enzymes or transporters. This study evaluated in vitro
      the effects of Devil's Claw on the multidrug transporter ABCB1/P-glycoprotein.
      MATERIALS AND METHODS: The effects of three commercially available Devil's Claw
      preparations and that of pure harpagoside were studied in the human kidney (HK-2)
      proximal tubule cell line, constitutively expressing ABCB1/P-glycoprotein (P-gp).
      Pgp activity and expression were tested by the calcein-AM test and by Western
      blotting, respectively. RESULTS: Commercial preparations inhibited P-gp activity,
      even if to a different extent, while pure harpagoside was almost ineffective. In
      cells cultured for three days in the presence of Devil's Claw preparations or
      pure harpagoside, a dose-dependent P-gp upregulation was found. CONCLUSIONS: Our
      results demonstrate for the first time that Devil's Claw may interact with the
      multidrug transporter ABCB1/P-gp, the effect not appearing strictly related to
      the harpagoside relative content. Modulation of both P-gp activity and P-gp
      expression by Devil's Claw raise the possibility of herb-drug interactions, to be
      further explored in depth.

PMID- 19577450
TI  - Hypoglycemic activity of dried extracts of Bauhinia forficata Link.
AB  - Leaves of the pantropical genus Bauhinia (Fabaceae) are known popularly as cow's
      foot, due to their unique characteristic bilobed aspect. The species Bauhinia
      forficata (Brazilian Orchid-tree) is widely used in folk medicine as an
      antidiabetic. The present work investigates the hypoglycemic activity of the
      dried extracts of Bauhinia forficata leaves in vivo, as well as the influence of
      the drying and granulation processes on this activity. The fluid extract was
      dried to generate oven-dried (ODE), spray-dried (SDE) and wet granulation (WGE)
      extracts, with the aid of colloidal silicon dioxide and/or cellulose:lactose
      mixture. The dried extracts were characterized by spectrophotometric,
      chromatographic and photo microscopy image analysis. 200 mg/kg body wt., p.o. of
      each dried product were administered orally to male Wistar rats over 7 days old,
      for biomonitoring of the hypoglycemic activity profile. The effect of the
      extracts was studied in STZ-induced diabetic rats. After 7 days of treatment,
      fasting glucose was determined, and the livers were removed, dried on tissue
      paper, weighed, and stored at -20 degrees C to estimate hepatic glycogen. Our
      results show that spray-drying or oven-drying processes applied to B. forficata
      extracts did not significantly alter its flavonoid profile or its hypoglycemic
      activity. Indeed, the dried extracts of B. forficata act differently from
      glibenclamide. Despite the lower active content in WGE, because of the higher
      concentration of adjuvants, the use of the granulation process improved the
      manufacturing properties of the ODE, making this material more appropriate for
      use in tablets or capsules.

PMID- 19577449
TI  - Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol,
      attenuates mast cell degranulation.
AB  - IgE-targeting therapy could provide significant progress in the treatment of
      allergic inflammation. In this study, we examined the effect of cycloartenyl
      ferulate (cycloartenol ferulic acid ester; CAF), a natural product from rice bran
      oil-derived gamma-oryzanol, on allergic reaction. When CAF and gamma-oryzanol
      were injected intradermally with anti-DNP IgE into the dorsal skin of rats, the
      passive cutaneous anaphylaxis reaction induced by DNP-HSA was attenuated. CAF and
      gamma-oryzanol also inhibited the degranulation of DNP-IgE sensitized RBL-2H3
      mast cells stimulated with anti-DNP-HSA. IgE conjugated with CAF could not be
      detected by anti-IgE antibody in the ELISA analysis. Although incubation of IgE
      with CAF did not decrease the amount of IgE, it was possible to precipitate IgE
      by centrifugation. These results demonstrate that CAF captures IgE, prevents it
      from binding to FcepsilonRI, and attenuates mast cell degranulation.

PMID- 19577451
TI  - Neuroprotective effects of Dendrobium alkaloids on rat cortical neurons injured
      by oxygen-glucose deprivation and reperfusion.
AB  - In this study we investigated the protective effects of alkaloids from Dendrobium
      spez. on cortical neurons injured by oxygen-glucose deprivation/reperfusion
      (OGD/RP) in vitro. Rat primary cultured cerebral cortical neurons were
      investigated at different time points of OGD/RP. The MTT assay and the lactate
      dehydrogenase (LDH) release were used to determine cell viability. The
      concentration of intracellular free calcium [Ca(2+)](i) and mitochondrial
      membrane potential (MMP) were determined to evaluate the degree of neuron damage.
      Morphologic changes of neurons following OGD/RP were examined by electron
      microscope. To evaluate neuron apoptosis, flow cytometry was performed and the
      expressions of caspase-3 and caspase-12 mRNA were examined by real-time
      quantitative PCR during OGD 2h/RP 12h. Treatment with Dendrobium alkaloids (0.025
      approximately 2.5mg/l) significantly attenuated neuronal damage, with evidence of
      increased cell viability, decreased cell apoptosis, and decreased cell
      morphologic impairment. Furthermore, Dendrobium alkaloids inhibited [Ca(2+)](i)
      elevation, increased MMP and decreased the expressions of caspase-3 and caspase
      12 in a concentration-dependent manner at OGD 2h/RP 12h. Dendrobium alkaloids
      have significantly protective effects on OGD/RP-induced neuronal damages in rat
      primary neuron cultures. The protection against OGD/RP-induced apoptosis appears
      to be mediated through blocking the decrease in MMP and increase in [Ca(2+)](i),
      as well as by down-regulating mRNA expression of caspase-3 and caspase-12.

PMID- 19577452
TI  - Activity of (-)alpha-bisabolol against Leishmania infantum promastigotes.
AB  - Many of the drugs used to treat leishmaniasis are associated with numerous
      adverse effects. Agents of natural origin have shown activity against different
      parasites. With this background, an in vitro study was conducted on the activity
      of (-)alpha-bisabolol, the principal component of Chamomilla recutita essential
      oil, against Leishmania infantum promastigotes, the main species responsible for
      human leishmaniasis in Spain. At the two highest concentrations tested (1000 and
      500mug/ml), (-)alpha-bisabolol and pentamidine (control agent) achieved 100%
      inhibition of L. infantum promastigote. These in vitro data can be considered
      promising in support of the therapeutic use of (-)alpha-bisabolol preparations to
      treat leishmaniasis caused by L. infantum species.

PMID- 19577453
TI  - Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype
      selectivity.
AB  - The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese
      medicine, has been applied as a tonic or an aphrodisiac agent and commonly used
      as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our
      study, the estrogen receptor subtype-selective activities of the extracts and
      compounds derived from PCL were analyzed using the HeLa cell assay. The different
      fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH
      extract of PCL showed significant activity in activating either ERalpha or ERbeta
      whereas the n-BuOH fraction showed no estrogenic activity. Further
      chromatographic purification of the active fractions yielded seven compounds
      including the two coumarins isopsoralen and psoralen, the four flavonoids
      isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene
      phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M)
      acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M)
      activated both ERalpha and ERbeta. The estrogenic activities of all compounds
      could be completely suppressed by the pure estrogen antagonist, ICI 182,780,
      suggesting that the compounds exert their activities through ER. Only psoralen
      and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation
      significantly. Although all the compounds have estrogenic activity, they may
      exert different biological effects. In conclusion, both ER subtype-selective and
      nonselective activities in compounds derived from PCL suggested that PCL could be
      a new source for selective estrogen-receptor modulators.

PMID- 19577454
TI  - Evidences for antiosteoporotic and selective estrogen receptor modulator activity
      of silymarin compared with ethinylestradiol in ovariectomized rats.
AB  - Recently, growing multiple uses of silymarin (SIL) as a complementary and
      alternative medicine, for alcohol-induced liver disease, acute and chronic viral
      hepatitis, as well as some other nonhepatic indications have been reported.
      Therefore, more attention should be paid for the hormonal side effects of SIL.
      Since the available data on the possible estrogenic effects of SIL is rather
      rare, this study aimed to further elucidate the different estrogenic effects and
      antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were
      treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and
      body weight were measured in all animals. Biochemical markers of bone formation
      (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin),
      endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle
      stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total
      cholesterol and total lipids were estimated. Formalin fixed femora and uteri
      specimens were used for histopathological examination. In addition, the binding
      property of SIL to the two estrogen receptors (ER) subtypes was tested by
      molecular docking. EE (strong) and SIL (mild) stimulated uterine weight
      (increased uterus hyperplastic endometrial glands) but EE only prevented body
      weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in
      protection of trabecula thickness, decreased serum levels of ALP and increased
      serum levels of both calcium and phosphorus. In contrast to EE, SIL did not
      decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol,
      total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum
      PTH. The docking study revealed a high affinity of SIL towards ERbeta. In
      conclusion, findings derived in the present study presented an overview of SIL
      many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in
      rats induced by OVX with mild proliferative effects in uterus. The observed
      effects may be due to additive beneficial effect of SIL on bone either due to
      direct interaction with ERbeta or increasing bone formation parameters including
      calcium, phosphorus, osteocalcin and PTH.

PMID- 19577455
TI  - Aged garlic extract delays the appearance of infarct area in a cerebral ischemia
      model, an effect likely conditioned by the cellular antioxidant systems.
AB  - Experimental evidence has shown that some garlic-derived products have a
      protective effect against ischemic brain injury. The present study was designed
      to investigate the effect of aged garlic extract (AGE), establish the therapeutic
      window, and determine its protective mechanism in a cerebral ischemia model.
      Animals were subjected to middle cerebral artery occlusion (MCAO) for 2h and
      treated with 1.2ml/kg body wt.(i.p.) of AGE 30min before, at the beginning of
      (0R), or 1h after reperfusion. The 0R treatment significantly reduced the size of
      the infarct area after 2h of reperfusion. Repeated doses subsequent to the 0R
      treatment (at 1, 2, or 3h after reperfusion) had no effect on the temporal window
      of protection. The protective 0R treatment with AGE prevented the increase in
      nitrotyrosine and the decrease in total superoxide dismutase, glutathione
      peroxidase, and extracellular superoxide dismutase activities induced by MCAO.
      These data indicate that AGE delays the effects of ischemia/reperfusion-induced
      neuronal injury. However, this treatment itself was not associated with a
      noticeable improvement in the neurological outcome, or with an effect on the
      inflammatory response. We conclude that the neuroprotective effect of AGE in the
      0R treatment might be associated with control of the free-radical burst induced
      by reperfusion, preservation of antioxidant enzyme activity, and the delay of
      other pathophysiological processes.

PMID- 19577457
TI  - Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro
      and in vivo.
AB  - A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones
      (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula
      diversivittata were studied for their possible inhibitory effects on Epstein-Barr
      virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13
      acetate (TPA). All of the tested compounds were active against EBV-EA activation.
      Among these compounds diversin (IC(50): 7.7) exhibited the strongest inhibitory
      effect and was selected to examine its effects on in vivo two-stage mouse skin
      carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and
      TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited
      papilloma formation up to week 7 and the percentage of papilloma bearers was
      approximately 93.3% at week 20. The average number of papillomas formed per mouse
      was only 5.5 even at week 20. The results of the present investigation indicated
      that diversin might be valuable as a potent cancer chemopreventive agent and its
      potency was comparable with those of curcumin and quercetin, two well-known
      cancer chemopreventive agents.

PMID- 19577456
TI  - Inhibition of warfarin hydroxylation by major tanshinones of Danshen (Salvia
      miltiorrhiza) in the rat in vitro and in vivo.
AB  - Danshen (Salvia miltiorrhiza) is commonly used in the treatment of cardiovascular
      and cerebrovascular diseases. In this study, the effects of a Danshen ethyl
      acetate extract containing the major tanshinones, an aqueous extract containing
      salvianolic acid B and danshensu, and individual tanshinones (tanshinone I,
      tanshinone IIA and cryptotanshinone) on warfarin hydroxylation was investigated.
      In rat liver microsomes study, the ethyl acetate extract of Danshen, tanshinone
      I, tanshinone IIA and cryptotanshinone decreased the formation of 4'-, 6- and 7
      hydroxy-warfarin, mediated by CYP1A1, CYP2C6 and CYP2C11 activities,
      respectively. The aqueous extract of Danshen had no effect on warfarin
      hydroxylation. Both acute and 3-day Danshen treatment significantly decreased
      Cmax and prolonged Tmax of warfarin in the rats. The formation of 4'- and 7
      hydroxywarfarin in vivo was decreased significantly after 3-day danshen
      treatment. In steady state study in vivo, the steady state plasma warfarin
      concentration was increased by 23% when Danshen was co-administered. The results
      suggest that tanshinones inhibited CYP1A1, CYP2C6 and CYP2C11-mediated warfarin
      metabolism both in vitro and in vivo in the rats. The timing of Danshen intake
      relative to warfarin contributed to different pharmacokinetics of the free
      warfarin concentration.

PMID- 19577458
TI  - Aerobic exercise capacity in COPD patients with and without pulmonary
      hypertension.
AB  - Pulmonary hypertension is a common occurrence in advanced COPD, but its effects
      on exercise capacity remain undetermined. Exercise testing and an
      echocardiographic examination were performed in 29 patients with advanced stable
      COPD. Mean pulmonary artery pressure (mPAP) was calculated from the acceleration
      time of pulmonary flow. Exercise capacity was evaluated by the distance walked in
      6 min (6MWD) and by an incremental cardiopulmonary exercise test (CPET). The
      patients had a forced expiratory volume in 1s of 1.13+/-0.49 L, and a 6MWD of
      305+/-66 m (mean+/-SD). The CPET (n=24) showed a: maximum workload of 52+/-25 W,
      a peak O(2) uptake of 13.8+/-4.4 mL/kg/min, a peak heart rate of 127+/-22 bpm, a
      peak respiratory exchange ratio 1.06+/-0.11, a ventilation (V(E))/CO(2)
      production slope of 37+/-11, and a peak O(2) pulse 7.5+/-2.3 mL. The peak V(E)
      was 41+/-15 L/min, and the calculated maximum voluntary V(E) 45+/-20 L/min. There
      was no difference in any of the CPET variables and 6MWD between the patients with
      a mPAP<30 mm Hg (mPAP 22+/-6 mm Hg, n=15) and those with a mPAP>30 mm Hg (mPAP
      38+/-6 mm Hg, n=14). There was no correlation between PAP and any of the exercise
      measurements. These results suggest that exercise capacity in unselected patients
      with advanced COPD and mild to moderate pulmonary hypertension is essentially
      limited by exhaustion of the ventilatory reserve.

PMID- 19577459
TI  - Recycling and recovery routes of plastic solid waste (PSW): a review.
AB  - Plastic solid waste (PSW) presents challenges and opportunities to societies
      regardless of their sustainability awareness and technological advances. In this
      paper, recent progress in the recycling and recovery of PSW is reviewed. A
      special emphasis is paid on waste generated from polyolefinic sources, which
      makes up a great percentage of our daily single-life cycle plastic products. The
      four routes of PSW treatment are detailed and discussed covering primary (re
      extrusion), secondary (mechanical), tertiary (chemical) and quaternary (energy
      recovery) schemes and technologies. Primary recycling, which involves the re
      introduction of clean scrap of single polymer to the extrusion cycle in order to
      produce products of the similar material, is commonly applied in the processing
      line itself but rarely applied among recyclers, as recycling materials rarely
      possess the required quality. The various waste products, consisting of either
      end-of-life or production (scrap) waste, are the feedstock of secondary
      techniques, thereby generally reduced in size to a more desirable shape and form,
      such as pellets, flakes or powders, depending on the source, shape and usability.
      Tertiary treatment schemes have contributed greatly to the recycling status of
      PSW in recent years. Advanced thermo-chemical treatment methods cover a wide
      range of technologies and produce either fuels or petrochemical feedstock.
      Nowadays, non-catalytic thermal cracking (thermolysis) is receiving renewed
      attention, due to the fact of added value on a crude oil barrel and its very
      valuable yielded products. But a fact remains that advanced thermo-chemical
      recycling of PSW (namely polyolefins) still lacks the proper design and kinetic
      background to target certain desired products and/or chemicals. Energy recovery
      was found to be an attainable solution to PSW in general and municipal solid
      waste (MSW) in particular. The amount of energy produced in kilns and reactors
      applied in this route is sufficiently investigated up to the point of operation,
      but not in terms of integration with either petrochemical or converting plants.
      Although primary and secondary recycling schemes are well established and widely
      applied, it is concluded that many of the PSW tertiary and quaternary treatment
      schemes appear to be robust and worthy of additional investigation.

PMID- 19577460
TI  - A microfluidic biosensor based on competitive protein adsorption for
      thyroglobulin detection.
AB  - We report a microfluidic sensing platform for the detection of thyroglobulin (Tg)
      using competitive protein adsorption. Serum Tg is a highly specific biomarker for
      residual thyroid tissue, recurrence and metastases after treatment for
      differentiated thyroid cancer (DTC). Conventional Tg detection techniques require
      complicated immobilization of antibodies and need to form a sandwich assay using
      additional secondary antibodies to enhance the sensitivity. We present a
      fundamentally different sensing technique without using antibody immobilization
      on a microfluidic platform. We engineer two surfaces covered by two known
      proteins, immunoglobulin G (IgG) and fibrinogen, with different affinities onto
      the surfaces. The microfluidic device offers a selective protein sensing by being
      displaced by a target protein, Tg, on only one of the surfaces. By utilizing the
      competitive protein adsorption, Tg displaces a weakly bound protein, IgG;
      however, a strongly bound protein, fibrinogen, is not displaced by Tg. The
      surface plasmon resonance (SPR) sensorgrams show that five human serum proteins,
      albumin, haptoglobin, IgG, fibrinogen and Tg, have different adsorption strengths
      to the surface and the competitive adsorption of individuals controls the
      exchange sequence. The adsorption and exchange are evaluated by fluorescent
      labeling of these proteins. Tg in a protein mixture of albumin, haptoglobin, and
      Tg is selectively detected based on the exchange reaction. By using the
      technique, we obviate the need to rely on antibodies as a capture probe and their
      attachment to transducers.

PMID- 19577461
TI  - Potential oilseed crops from the semiarid region of northeastern Brazil.
AB  - The caatinga semi-arid ecosystem of northeastern Brazil is characterized by a
      dry, spiny and predominantly deciduous shrub/forest vegetation, and many species
      there are potential sources of renewable resources for the oleochemical industry.
      The present research determined the oil content and fatty acid profiles of seeds
      from eight caatinga species. Seed oils were extracted in a Soxhlet system, and
      their fatty acid content identified by GC-MS. Oil content varied between 20.2% in
      Tabebuia impetiginosa (Mart.) Standl. (Bignoniaceae) and 46.4% in Barnebya
      harleyi (W.R. Anderson & B. Gates) Malpighiaceae. Anemopaegma laeve DC.
      (Bignoniaceae) had the highest oleic acid content (63.4%), while high levels of
      linoleic acid were found in Banisteriopsis pubipetala (Juss.) Cuatrec. (42.8%)
      and B. harleyi (31.9%) (both Malpighiaceae). Palmitic acid was the major fatty
      acid (50%) in Hippocratea volubilis (L.) (Celastraceae). High levels of linoleic
      and linolenic acids were found in Croton adamantinus Mull. Arg. (Euphorbiaceae),
      averaging 44.2% and 45.2% respectively. Gadoleic acid in was the most abundant
      fatty acid in the oil produced by Serjania lethalis A. St. Hill. (Sapindaceae),
      averaging 69.6%. B. pubipetala, B. harleyi, C. adamantinus, and H. volubilis were
      identified as promising species for cultivation.

PMID- 19577463
TI  - Effects of UV pretreatment on microbial community structure and metabolic
      characteristics in a subsequent biofilter treating gaseous chlorobenzene.
AB  - To provide insight into effects of UV pretreatment on microorganisms in
      subsequent biofilters, the changes of microbial community structure and metabolic
      characteristics of biofilters with (UV-BF) and without (BF) UV pretreatment were
      studied. The respiratory quinone and BIOLOG methods were used to analyze
      microbial community structure and metabolic characteristics, respectively. The
      results indicated the quinone profiles, the species of dominant quinone and its
      molar fraction of the biofilm in both biofilters showed different behaviors.
      Ubiquinones-8 and menaquinone-9(H(2)) was the dominant quinones in BF and UV-BF
      processes, respectively. The dissimilarity index of two biofilters markedly
      increased to nearly 60 after turning on the UV lamp. The microbial samples from
      UV-BF process showed higher metabolic activities of 0.040 cm(-1) h(-1) than 0.028
      cm(-1) h(-1) in BF process. Moreover, the microorganisms in both biofilters
      demonstrated distinct metabolic characteristics. Further, the performance of
      biofilters showed good correlation with microbial community structure and
      metabolic characteristics.

PMID- 19577462
TI  - Mono fermentation of grass silage by means of loop reactors.
AB  - A loop reactor was operated for mono fermentation of grass silage without manure
      addition under mesophilic conditions (38 degrees C). An averaged specific biogas
      production of 0.50 m(N)(3) per kg volatile solids (VS) with a methane
      concentration of 52% at an organic loading rate of up to 3.5 kg(VS)/(m(3) d) was
      obtained. The retention time varied from 440 days at 1.0 kg(VS)/(m(3) d) to 50
      days at 3.5 kg(VS)/(m(3) d). The degradation level was more than 60% based on VS
      and 75% based on COD. The first-order hydrolysis rate constant of the process was
      estimated to be 0.6 d(-1). Despite the relative high ammonium concentration of up
      to 4 g/l, the system worked stable for an operation period of 310 days. In
      particular the TS content in the fermenter was found to be a key parameter and
      should not exceed 12% in order to avoid instabilities.

PMID- 19577464
TI  - Valorisation of wastepaper using the fibrolytic/hydrogen producing bacterium
      Ruminococcus albus.
AB  - The present study aimed to investigate the biotransformation of different kinds
      of wastepaper to hydrogen by the fibrotylic bacterium Ruminococcus albus. Five
      different types i.e. paper tissue, office paper, illustrated magazine paper,
      paperboard and newspaper, were selected as representatives of the most common
      types of wastepaper found in municipal solid wastes. The percentage of total
      carbohydrates measured as glucose equivalents, ranged from 50% to 100% (w/w),
      whereas the bioconversion by R. albus ranged from 18% to 100% of their initial
      weigh. The only metabolic products detected in all cases were acetate, ethanol,
      formate, hydrogen and carbon dioxide. The hydrogen yields ranged from 46 to 280 L
      H(2)/kg paper, indicating that wastepaper could be a promising candidate for
      second generation biohydrogen production. Subsequently, hydrolysis was
      investigated for paper tissue and paperboard. It was shown that in both cases the
      degradation process could be satisfactory described by zero order kinetics and it
      was identified to be the rate limiting step for the whole process, controlling
      biomass growth and metabolites generation rate.

PMID- 19577465
TI  - Long-term operation of a partial nitritation pilot plant treating leachate with
      extremely high ammonium concentration prior to an anammox process.
AB  - The goal of this work was to demonstrate the feasibility of treating leachate
      with high ammonium concentrations using the SBR technology, as a preparative step
      for the treatment in an anammox reactor. The cycle was based on a step-feed
      strategy, alternating anoxic and aerobic conditions. Results of the study
      verified the viability of this process, treating an influent with concentration
      up to 5000 mg N-NH(4)(+) L(-1). An effluent with about 1500-2000 mg N-NH(4)(+) L(
      1) and 2000-3000 mg N-NO(2)(-) L(-1) was achieved, presenting a nitrite to
      ammonium molar ratio close to the 1.32 required by the anammox. Furthermore,
      taking advantage of the biodegradable organic matter, the operational strategy
      allowed denitrifying about 200 mg N-NO(2)(-) L(-1). The extreme operational
      conditions during the long-term resulted on the selection of a sole AOB
      phylotype, identified by molecular techniques as Nitrosomonas sp. IWT514.

PMID- 19577466
TI  - Short-term impact of dry olive mill residue addition to soil on the resident
      microbiota.
AB  - The short-term response of the resident soil bacterial and fungal communities to
      the addition of 5% (w/w) of either dry olive mill residue (DOR), DOR treated with
      Phlebia sp. (PTDOR) or DOR previously extracted with water (WEDOR) was
      investigated. As opposed to bacteria, the diversity of fungi increased upon the
      amendments as assessed by denaturing gradient gel electrophoresis of 18S rDNA.
      Over the first 30 days, phospholipid fatty acids analyses indicated a gradual
      decrease in the relative abundances of gram(+) bacteria (from 44.8% to 37.9%) and
      a concomitant increase of gram(-) bacteria (from 37.3% to 51.2%) in DOR-amended
      soil. A considerable increase in the fungal/bacterial ratio was observed after 7
      days in DOR, WEDOR and PTDOR-amended soils with respect to the control (0.316,
      0.165 and 0.265, respectively, vs. 0.011). The overall microbial activity was
      stimulated by the amendments as indicated by the higher activity levels of both
      dehydrogenase and fluorescein diacetate hydrolase. These results indicate that
      DOR at the application level examined is not toxic on soil microorganisms.

PMID- 19577467
TI  - Synthesis, radiolabeling and preliminary in vivo evaluation of [18F]FE-PE2I, a
      new probe for the dopamine transporter.
AB  - A new dopamine transporter (DAT) ligand, (E)-N-(3-iodoprop-2-enyl)-2beta
      carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane (FE-PE2I, 6), derived from
      PE2I (1), was prepared and found to be a potent inhibitor of rodent DAT in vitro.
      Compound 6 was radiolabelled with fluorine-18 (t(1/2)=109.8 min) for PET studies
      in monkeys. In vivo PET measurements showed a regional distribution in brain that
      corresponds to the known distribution of DAT. This binding was specific,
      reversible and the kinetics of [(18)F]6 binding in brain were faster than for its
      lead compound, [(11)C]1. The possible presence of a hydroxymethyl-radiometabolite
      formed by oxidation in the 3beta-benzylic position of [(18)F]6 warrants further
      detailed evaluation of the metabolism of [(18)F]6. [(18)F]6 is a potential
      radioligand for imaging DATs in the human brain with PET.

PMID- 19577468
TI  - The identification of potent, orally bioavailable tricyclic CGRP receptor
      antagonists.
AB  - A series of tricyclic CGRP receptor antagonists was optimized in order to improve
      oral bioavailability. Attenuation of polar surface area and incorporation of a
      weakly basic indoline nitrogen led to compound 5, a potent antagonist with good
      oral bioavailability in three species.

PMID- 19577471
TI  - Controlled vocabularies for microbial virulence factors.
AB  - Knowledge about pathogenesis is increasing dramatically, and most of this
      information is stored in the scientific literature or in sequence databases. This
      information can be made more accessible by the use of ontologies or controlled
      vocabularies. Recently, several ontologies, controlled vocabularies and databases
      have been developed or adapted for virulence factors and their roles in
      pathogenesis. Here, we discuss these systems, how they are being used in research
      and the challenges that remain for developing and applying ontologies for
      virulence factors.

PMID- 19577469
TI  - Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD)
      inhibitors.
AB  - Two structurally distinct series of SCD (Delta9 desaturase) inhibitors (1 and 2)
      have been previously reported by our group. In the present work, we merged the
      structural features of the two series. This led to the discovery of compound 5b
      (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay
      (IC(50)=6nM). This compound has 78% oral bioavailability in rats and is
      preferentially distributed into liver (76 times vs plasma) with relatively low
      brain penetration. In a five-day study (sucrose fed rats) compound 5b
      significantly reduced SCD activity in a dose-dependent manner as determined by GC
      analysis of fatty acid composition in plasma and liver, and significantly reduced
      liver triglycerides versus the control group ( approximately 50%).

PMID- 19577470
TI  - Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based
      inhibitors of human neutrophil elastase.
AB  - The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3
      yl)-benzo[d][1,3]oxazin-4-one is described. A structure-activity relationship
      study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5
      ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl
      piperazin-1-yl)-pyridin-3-yl] derivatives of this core were shown to yield HNE
      inhibitors of similar potency with significantly different stabilities in rat
      plasma.

PMID- 19577473
TI  - Applying the Gene Ontology in microbial annotation.
AB  - The ever-increasing number of microbial sequencing projects necessitates a
      standardized system for the capture of genomic data to ensure that the flood of
      information produced can be effectively utilized. The Gene Ontology (GO) provides
      the standard for gene product annotations in the areas of molecular function,
      biological process and cellular component. A recent effort by the Plant
      Associated Microbe Gene Ontology (PAMGO) Consortium has produced more than 800
      new GO terms specific for annotating interactions between microbes and their
      hosts and other symbiotic interactions. In addition, there have been changes and
      additions to the GO annotation format and evidence storage system to reflect the
      needs of the microbial annotation community. The capture of annotation
      information with systems like the GO is absolutely essential to enable the
      efficient mining of annotation information across diverse genomes and thus to
      further biological research in meaningful ways.

PMID- 19577472
TI  - Functional annotations for the Saccharomyces cerevisiae genome: the knowns and
      the known unknowns.
AB  - The quest to characterize each of the genes of the yeast Saccharomyces cerevisiae
      has propelled the development and application of novel high-throughput (HTP)
      experimental techniques. To handle the enormous amount of information generated
      by these techniques, new bioinformatics tools and resources are needed. Gene
      Ontology (GO) annotations curated by the Saccharomyces Genome Database (SGD) have
      facilitated the development of algorithms that analyze HTP data and help predict
      functions for poorly characterized genes in S. cerevisiae and other organisms.
      Here, we describe how published results are incorporated into GO annotations at
      SGD and why researchers can benefit from using these resources wisely to analyze
      their HTP data and predict gene functions.

PMID- 19577474
TI  - Understanding animal viruses using the Gene Ontology.
AB  - Understanding the effects of viral infection has typically focused on specific
      virus-host interactions such as tissue tropism, immune responses and
      histopathology. However, modeling viral pathogenesis requires information about
      the functions of gene products from both virus and host, and how these products
      interact. Recent developments in the functional annotation of genomes using Gene
      Ontology (GO) and in modeling functional interactions among gene products,
      together with an increased interest in systems biology, provide an excellent
      opportunity to generate global interaction models for viral infection. Here, we
      review how the GO is being used to model viral pathogenesis, with a focus on
      animal viruses.

PMID- 19577475
TI  - Manifestation, management and outcome of subclinical pituitary adenoma apoplexy.
AB  - The objective of this study was to investigate the clinical features, diagnosis,
      treatment and outcomes of subclinical pituitary adenoma apoplexy (SPAA) in 185
      consecutive patients between January 1990 and May 2007. Of the 185 patients, 133
      (71.89%) underwent transsphenoidal tumor decompression and the remaining 52
      patients (28.11%) underwent transcranial surgery. Preoperative and postoperative
      endocrinological hormone concentrations were measured in all patients. Pituitary
      imaging was obtained by CT scans or MRI. Follow-up outcomes were obtained from
      the records of outpatient visits and by telephone interviews. Visual disturbance,
      headache and pituitary function impairment improved significantly in all
      patients. Prolactinoma was the most frequent type of pituitary adenoma in our
      series (51.89%). SPAA usually occurred in patients with large or giant adenomas
      (85.95%). Postoperative follow-up ranged from 1 year to 17 years with a mean of
      7.4+/-1.6 years. The tumor recurred in 23 patients, 18 of whom were treated with
      postoperative radiotherapy for either residual tumors (n=8) or recurrence (n=10).
      Long-term thyroid hormone replacement was necessary in eight patients and steroid
      hormone replacement in six patients. The incidence of SPAA is relatively high
      compared with that of acute pituitary apoplexy. The exact pathogenic mechanism of
      SPAA remains unknown. MRI is significantly better than CT scans for detection of
      SPAA. Transsphenoidal decompression is safe and effective. Surgical decompression
      should be performed as early as possible.

PMID- 19577477
TI  - Silicone spaghetti.
AB  - Migration of ventriculoperitoneal shunt catheters, although infrequent, is well
      reported. We report the unusual event of a patient who, after having had three
      shunt revisions over a 15-year period, presented with a per-oral extrusion of her
      original distal catheter.

PMID- 19577476
TI  - Olfactory groove meningiomas: approaches and complications.
AB  - Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial
      meningiomas. We report 21 patients with OGMs. Tumors were operated on using three
      surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and
      fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved
      in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%.
      The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%.
      We preferred to use the pterional approach, which provides quick access to the
      tumor with less brain exposure. It also allows complete drainage of cisternal
      cerebrospinal fluid, providing a good level of brain relaxation during surgery.
      However, for long, thin tumors, hemostasis can be difficult using this approach.

PMID- 19577478
TI  - Evoked magnetic fields as a tool to optimize therapeutic electrical stimulation
      of the sacral surface.
AB  - Magnetoencephalography (MEG) was used to measure the somatosensory evoked fields
      in six healthy males undergoing sacral surface therapeutic electrical
      stimulation, a recently introduced treatment for chronic urinary dysfunction.
      This study was performed to investigate the utility of MEG to optimize the
      stimulation parameters. Strong or weak electrical stimuli were applied to small
      or large surface electrodes placed over the bilateral sacral surfaces. The peak
      latency and strength of the equivalent current dipole were evaluated at the first
      peak originating from the primary somatosensory cortex (M30). There was no
      difference in M30 latency in response to stimulation intensity or electrode size.
      However, a larger equivalent current dipole strength was obtained in response to
      higher stimulus intensities, which indicated a more effective stimulus on the
      sacral surface. The present MEG study shows that stronger stimuli given through
      large electrodes evoke larger responses than small stimuli through small
      electrodes. The study also suggests that MEG can be used as an objective tool to
      monitor whether therapeutic stimulation parameters are appropriate.

PMID- 19577479
TI  - An evaluation of Compton suppression neutron activation analysis for
      determination of trace elements in some geological samples.
AB  - Compton suppressed neutron activation analysis has been used for a variety of
      applications, but never has a detailed discussion of its use in far more complex
      matrices, such as geological samples, been fully addressed. This investigation
      seeks to serve as a qualitative evaluation of Compton suppression neutron
      activation analysis (CSNAA) and to illustrate the benefits of using Compton
      suppression with thermal and epithermal neutrons for the analysis of several
      geological specimens.

PMID- 19577481
TI  - The role of immunity in elderly cancer.
AB  - The increased incidence of malignancies in elderly patients living in
      industrialized countries has led to both identify the causes that alter the
      normal homeostatic balance in elderly and designate the specific treatments. The
      progressive decline of the immune system (immunosenescence) involving cellular
      and molecular alterations impact both innate and adaptive immunity. The
      immunosenescence leads to increased incidence of infectious diseases morbidity
      and mortality as well as heightened rates of other immune disorders such as
      autoimmunity, cancer, and inflammatory conditions. Here, we summarize the
      knowledge on the major changes in the immune system associated with aging in
      primary lymphoid organs as well as a description of molecular mechanisms, and the
      impact on cancer development.

PMID- 19577480
TI  - A 4-year retrospective study of facial fractures on Jeju, Korea.
AB  - A number of researchers from various regions have reported statistical and
      clinical studies of facial fractures. The results of those studies show slight
      differences depending on regional, cultural, social and economic backgrounds.
      This report presents a statistical analysis of facial fractures occurring over 4
      years on Jeju, Korea. The statistics come from the 318 patients who presented to
      Cheju National University Hospital for facial fractures, and ours is a
      retrospective study analyzing patient ages, gender, fracture etiology, alcohol
      involvement and the anatomical site of the fracture. The most common cause of
      facial fractures on Jeju was violence (40.9%), followed by traffic accidents
      (17%). The most frequently fractured site was the nasal bone (42.5%). According
      to the Jeju Statistics Agency, the people of Jeju are highly dependent on alcohol
      and previous research has reported the close relationship between alcohol
      consumption and violence. We paid close attention to violence as a primary cause
      for facial fractures in the cultural and social context of Jeju. Data analysis
      regarding facial fractures may provide crucial information for recognition of
      causes and planning for prevention.

PMID- 19577482
TI  - Influence of frequent nocturnal home hemodialysis on food preference.
AB  - OBJECTIVE: Dialysis patients frequently report a change of taste that is
      reversible after renal transplantation, suggesting that uremic toxins may
      negatively influence taste. Currently, frequent nocturnal home hemodialysis
      (NHHD) is the most effective method of hemodialysis, and is associated with the
      lowest levels of uremic toxins. We studied preferences for various foods as an
      indicator of taste perception. We questioned whether food preference differs
      between NHHD patients and those on conventional hemodialysis. DESIGN AND
      PATIENTS: In this transverse, cross-sectional pilot study, we assessed food
      preference by means of a questionnaire for patients on NHHD (n=6; 8 hours of
      dialysis per night, for 5 or 6 nights a week) and 3 age-matched and sex-matched
      control groups: chronic home hemodialysis patients (HHD; n=9; 4 to 5 hours of
      dialysis per day, 3 days a week), chronic in-center hemodialysis patients (CHD;
      n=18; 4 to 5 hours of dialysis per day, 3 days a week), and healthy control
      subjects (HC; n=23). RESULTS: Mean scores for food preference did not differ
      between groups (P=.32). Similarly, the preference for product groups did not
      differ between groups. On an individual product level, we found only minor
      differences. The NHHD patients had a preference for savory snacks, as did the HC
      and CHD groups, whereas the HHD group had a preference for sweet snacks (P <
      .05). Hemodialysis patients reported dry mouth more often than did the HC
      patients (P < .05). CONCLUSIONS: Frequent NHHD has no major impact on food
      preference. The change in taste reported by NHHD patients is not related to their
      particular food preferences.

PMID- 19577483
TI  - Effects of soy consumption on oxidative stress, blood homocysteine, coagulation
      factors, and phosphorus in peritoneal dialysis patients.
AB  - OBJECTIVE: We studied the effects of soy consumption on oxidative stress, blood
      homocysteine, coagulation factors, and phosphorus in peritoneal dialysis
      patients. DESIGN: This was an unblinded, randomized clinical trial. SETTING: This
      study involved peritoneal dialysis centers in Tehran, Iran. PATIENTS: We included
      40 peritoneal dialysis patients (20 males and 20 females). INTERVENTION:
      Peritoneal dialysis patients were randomly assigned to either a soy or control
      group. Patients in the soy group received 28 g/day textured soy flour (containing
      14 g of soy protein) for 8 weeks, whereas patients in the control group received
      their usual diet, without any soy. MAIN OUTCOME MEASURES: Blood oxidized low
      density lipoprotein (ox-LDL), homocysteine, phosphorus, fibrinogen
      concentrations, and the activities of coagulation factors VII, IX, and X were
      measured at baseline and at the end of week 8 of the study. RESULTS: The
      percentage of plasma coagulation factor IX activity decreased significantly by
      17% in the soy group at the end of week 8 compared with baseline (P < .01), and
      the reduction was significant compared with the control group (P < .05). There
      were no significant differences between the two groups in mean changes of blood
      ox-LDL, homocysteine, phosphorus, fibrinogen concentrations, and the activities
      of coagulation factors VII and X. CONCLUSION: Soy consumption reduces plasma
      coagulation factor IX activity, which is a risk factor for thrombosis in
      peritoneal dialysis patients.

PMID- 19577484
TI  - Rationale for propofol use in cardiac surgery.

PMID- 19577485
TI  - Use of inhaled epoprostenol in transition to extubation in a patient after
      implantation of a ventricular assist device.

PMID- 19577486
TI  - Risk factors for mortality and ischemic heart disease in patients with long-term
      type 1 diabetes.
AB  - AIMS: The purpose of this study is to evaluate the effect of glycemic regulation,
      dyslipidemia, and renal dysfunction on mortality (all-cause and cardiovascular)
      and ischemic heart disease (IHD) in a long-term follow-up of a population-based
      cohort of Danish type 1 diabetic patients with at least 20 years of diabetes.
      METHODS: A population-based cohort of type 1 diabetic patients was identified as
      of July 1, 1973 (n=727). In 1993 to 1996, the cohort was reassessed and baseline
      data were collected from blood and urine samples in 389 patients. Mean (glycemic
      regulation and lipids) and highest values (creatinine and albuminuria) of the
      baseline period were used to predict mortality and IHD between baseline and 2006.
      Data of mortality and morbidity were provided by the Danish Civil Registration
      System, the Danish Causes of Death Registry, and the Danish National Patient
      Registry. RESULTS: At the follow-up in 2006, 256 patients (65.8%) were still
      alive. In a statistical model adjusted for age, sex and duration of diabetes, the
      following parameters were related to all-cause mortality and cardiovascular
      mortality: glycemic regulation, triglycerides, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol (inversely), total cholesterol,
      creatinine, and macroalbuminuria. Furthermore, all markers except
      macroalbuminuria were associated with IHD. Microalbuminuria at baseline was not
      related to any of the endpoints. CONCLUSIONS: Glycemic regulation, dyslipidemia,
      and renal dysfunction were all related to mortality and IHD in a 13-year follow
      up of long-term Danish type 1 diabetic patients. These results underscore the
      better outcome for tightly regulated type 1 diabetic patients, even in long-term
      survivors.

PMID- 19577487
TI  - Prevalence of impaired fasting glucose and analysis of risk factors in Han
      adolescents.
AB  - OBJECTIVE: To evaluate the prevalence of impaired fasting glucose (IFG) and its
      relationship with cardiovascular risk factors in Han adolescents aged 13 to 18
      years. METHODS: Step 1: A cross-sectional study was conducted on 3937 Han
      adolescents. IFG was defined as a fasting glucose of 5.6 to 7.0 mmol/l.
      Measurements included anthropometric measurements, fasting plasma glucose (FPG),
      and serum lipids. Step 2: We identified 60 adolescents with IFG from the IFG
      group using a random number table, and 60 adolescents with normal fasting glucose
      (NFG) were matched for age and gender with the random IFG sample. Serum true
      insulin (TI) was further measured. RESULTS: (1) The prevalence of IFG was 3.5%
      and was similar in boys and girls (3.9% vs. 3.1%, P=.177). The prevalence of IFG
      in adolescents with a family history of type 2 diabetes (FHD) was higher than in
      adolescents without FHD (6.3% vs. 2.5%, P=.000). (2) In logistic regression, the
      clustering of cardiovascular risk factors among adolescents with IFG was 1.889
      (95% CI: 1.125-3.171, P=.016) times compared with adolescents with NFG adjusted
      by age and gender. (3) Multiple linear regression analysis using FPG as the
      dependent variable showed that waist circumference (beta=0.003, P=.000) was a
      significant independent predictor. (4) In Step 2, the IFG group showed
      significantly higher levels of lnTI and lnHOMA-IR than the NFG group (P<.01). FPG
      was a significant independent predictor for lnTI (beta=0.478, P=.000) and lnHOMA
      IR (beta=0.671, P=.000). CONCLUSION: We found a high prevalence of IFG in Han
      adolescents. Genetic susceptibility and abdominal obesity were the main factors
      causing adolescent IFG. Adolescents with IFG increased the clustering of
      cardiovascular risk factors.

PMID- 19577488
TI  - The 1674+11C>T polymorphism of CHRNA4 is associated with juvenile myoclonic
      epilepsy.
AB  - The alpha4 subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor
      (nAChR), linked to an idiopathic partial epilepsy, autosomal dominant nocturnal
      frontal lobe epilepsy (ADNFLE), may also play a key role in the development of
      the idiopathic generalized epilepsy syndrome (IGE), juvenile myoclonic epilepsy
      (JME). This study was designed to explore an association of four polymorphisms of
      the CHRNA4 with JME in Polish children and young patients. The study included 92
      JME patients and 222 unrelated healthy individuals. In each group the frequencies
      of the CHRNA4 c.555C>T, c.594C>T, 1674(+11)C>T, and 1674(+14)A>G polymorphisms
      were determined using PCR-RFLP analyses. An association between the 1674(+11)C>T
      polymorphism of the CHRNA4 and JME was evidenced. Allele T (the risk factor)
      appeared with a significantly higher frequency in the JME patients than in the
      controls (p=0.0299). The patients harboring the 1674(+11)CT+TT genotypes showed
      an increased risk of JME (CT+TT versus CC: OR=1.925; 95% CI=1.021-3.629;
      p=0.0408). No association was found for the other CHRNA4 polymorphisms tested.
      The CHRNA4 1674(+11)C>T polymorphism may be a susceptibility factor for epilepsy,
      and its higher frequency in patients with juvenile myoclonic epilepsy suggests
      that the CHRNA4 may be one of the candidate genes for this epileptic syndrome.

PMID- 19577489
TI  - Essential oils as a cause of breakthrough seizure after temporal lobectomy.
AB  - Breakthrough seizures are often encountered in patients with well-controlled
      epilepsy for no obvious reason. We report a case of a breakthrough seizure after
      temporal lobectomy secondary to topical administration of essential oils. We
      recommend inquiring about the use of essential oils in patients with well
      controlled epilepsy who experience breakthrough seizures.

PMID- 19577491
TI  - Vascular access in the lower limb.

PMID- 19577490
TI  - Influence of warfarin on the success of endovenous laser ablation (EVLA) of the
      great saphenous vein (GSV).
AB  - BACKGROUND: Although warfarin is routinely stopped prior to varicose vein surgery
      the absence of incisions may make this unnecessary prior to EVLA. Nevertheless
      continuing therapy may compromise ablation rates resulting in treatment failure.
      Since EVLA is particularly suitable for older patients with co-morbidities this
      study investigates whether warfarin influences outcome. METHOD: A prospective
      observational cohort study was designed to assess ablation rates (1 year, duplex
      ultrasound), Aberdeen varicose vein symptom severity scores (AVVSS) and patient
      satisfaction following GSV EVLA in 22 patients ("warfarin group": 12 female, 10
      male; 24 limbs) taking warfarin and 24 age/sex and disease-severity matched
      controls who were not taking anticoagulants ("no-warfarin group"). RESULTS:
      Complete ablation of the treated-length of GSV was achieved in 20/24 (83%) limbs
      in the "warfarin group" versus 23/24 (96%) in the "no-warfarin" group (p=0.347,
      chi squared). Suboptimal energy densities were delivered to 3/4 failures in the
      "warfarin group". A similar, significant (p<0.001, Wilcoxon) improvement in AVVSS
      occurred in both groups [warfarin: median 14.6 (inter-quartile range 8.9-19.1) to
      3.8 (1.9-6.2), no-warfarin: median 13.9 (IQR 7.6-20.1) to 3.5 (2.2-6.4)].
      Patients were equally satisfied with outcomes (warfarin=92%, no-warfarin=90%;
      p=0.391, Mann-Whitney). No major complications occurred. CONCLUSIONS: EVLA in
      patients taking warfarin is safe and effective. Since cessation of therapy is
      unnecessary it should provide a valuable alternative to surgery in these
      patients.

PMID- 19577492
TI  - A pilot study of a simple screening technique for estimation of salivary flow.
AB  - OBJECTIVES: The purpose of this study was to develop a simple screening technique
      for estimation of salivary flow and to test the usefulness of the method for
      determining decreased salivary flow. STUDY DESIGN: A novel assay system
      comprising 3 spots containing 30 microg starch and 49.6 microg potassium iodide
      per spot on filter paper and a coloring reagent, based on the color reaction of
      iodine-starch and theory of paper chromatography, was designed. We investigated
      the relationship between resting whole salivary rates and the number of colored
      spots on the filter produced by 41 hospitalized subjects. RESULTS: A significant
      negative correlation was observed between the number of colored spots and the
      resting salivary flow rate (n = 41; r = -0.803; P < .01). For all complaints of
      decreased salivary flow (n = 9) having cutoff values <100 microL/min for the
      salivary flow rate, 3 colored spots appeared on the paper, whereas for healthy
      subjects there was < or =1 colored spot. CONCLUSION: This novel assay system
      might be effective for estimation of salivary flow not only in healthy but also
      in bedridden and disabled elderly people.

PMID- 19577493
TI  - Evaluation of the radiopacity of different root canal sealers.
AB  - OBJECTIVE: The aims of this study were to compare the radiopacity of 8 root canal
      sealers relative to gutta-percha and dentin in standard discs and to evaluate the
      effect of these sealers on the radiopacity of root canal fillings in simulated
      canals. STUDY DESIGN: Radiographs were taken of 1-mm-thick specimens of 8 root
      canal sealers (Diaket, Endion, MTA, Endofil, Roeko Seal, Sealite, AH26, AH Plus)
      and gutta-percha, a 1-mm-thick human tooth slice, and aluminum
      stepwedge.Simulated canals were used to evaluate the effect of the sealer on
      radiopacity of the root fillings. After enlargement of the simulated canals with
      ProTaper instrument, root canals were filled with these 8 sealers alone and with
      single ProTaper gutta-percha cone. Radiographs of all filled simulated canals
      were taken with an aluminum stepwedge. RESULTS: All the sealers demonstrated
      greater radiopacity than dentin (0.7940 mm Al) (P < .001). AH Plus showed the
      highest radiopacity in the standard disc group (Group 1) (8.9881 mm Al) (P <
      .001), and in the sealer group in simulated canals (Group 2) (9.2100 mm Al) (P <
      .001). In the sealer plus gutta-percha group in simulated canals (Group 3),
      Sealite plus gutta-percha showed greater radiopacity (8.4460 mm Al) (P < .001).
      CONCLUSION: Whether the opacity of the sealers alone is more or less than 3 mm
      Al, their radiopacity is increased when they are used in combination with gutta
      percha, because of its higher radiopacity. However, when sealers are used in
      conjunction with gutta-percha, they can affect the radiopacity of the root canal
      filling according to their type and thickness.

PMID- 19577494
TI  - Molecular characterization of thalassemia intermedia, due to co-inheritance of
      homozygous alpha triplication and IVSI-5 beta-thalassemia.

PMID- 19577495
TI  - A novel mutation in the flavin-containing monooxygenase 3 gene (FMO3) of a
      Norwegian family causes trimethylaminuria.
AB  - Loss-of-function mutations in the flavin-containing monooxygenase 3 gene (FMO3)
      cause the inherited disorder trimethylaminuria (TMAuria), or fish-odour syndrome.
      Here we describe the identification in a family from northern Norway of a novel
      causative mutation of TMAuria. A female child within the family presented with a
      TMAuria-like phenotype. The child and her mother were found to be heterozygous
      for a novel mutation (R238Q) in exon 6 of FMO3. The child's father lacked this
      mutation, but was heterozygous for a double polymorphic variant, E158K/E308G,
      which was not present in the child. During a consultation with her doctor the
      mother mentioned an uncle whom she remembered as having a strong body odour. This
      discussion led to genetic counselling of the uncle and analysis of his DNA showed
      him to be homozygous for the R238Q mutation. Analysis of the mutant FMO3
      expressed in bacteria revealed that the R238Q mutation abolished catalytic
      activity of the enzyme and is thus a causative mutation for TMAuria. The
      specificity constant (k(cat)/K(M)) of the K158/G308 variant was 43% of that of
      ancestral FMO3. Because the child is heterozygous for the R238Q mutation and no
      other mutation known to cause TMAuria was detected in her DNA she is predicted to
      suffer from transient childhood TMAuria, whereas her great-uncle has primary
      TMAuria.

PMID- 19577496
TI  - Human directed aggression in Brazilian domestic cats: owner reported prevalence,
      contexts and risk factors.
AB  - Aggression by cats towards humans is a serious behavioural, welfare and public
      health problem, although owners may believe it is an inevitable part of cat
      ownership. There has been little scientific investigation of the risk factors
      associated with this problem. One hundred and seven owners in the Sao Paulo
      region of Brazil, took part in a survey aimed at investigating the perceived
      prevalence of the problem, defining the most common contexts of human directed
      aggression and identifying associated potential risk factors. Human directed
      aggression occurred in 49.5% of cats and was most commonly associated with
      situations involving petting and play, followed by protection of a resource, when
      startled, when observing an unfamiliar animal and least commonly when unfamiliar
      people were present. Pedigree status, neuter status, a history of early trauma,
      sensitivity to being stroked, the absence of other cats in the home, relationship
      with other animals, level of background activity at home, access to the outside
      and tendency to be alone (meaning tendency to staying far from the family
      members) were all associated with an increased risk in one or more context.
      However, sex, age, age when acquired, source of pet, attachment to a specific
      household member, type of domestic accommodation, relationship with another cat
      if present and contact with other animals did not appear to increase the risk.
      The results suggest sensitivity to being stroked and background levels of stress
      in the home are the most pervasive risk factors, and future research should aim
      to investigate these factors further. These data are of relevance when advising
      owners about the risk and development of this problem.

PMID- 19577498
TI  - Thermal antinociception after dexmedetomidine administration in cats: a
      comparison between intramuscular and oral transmucosal administration.
AB  - Dexmedetomidine 40microg/kg was administered either intramuscularly (IM) or oral
      transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal
      nociceptive thresholds and visual analogue scale (VAS) sedation scores were
      obtained before and at regular intervals up to 24h after test drug
      administration. The summary measures of overall mean threshold, overall mean VAS
      sedation plus onset, offset and duration of analgesia were investigated using a
      univariate general linear model. There were no significant differences between
      treatment groups. Data are presented as mean+/-standard deviation: delta T mean
      increase over time (IM 6 degrees C+/-3 degrees C, OTM 6 degrees C+/-2 degrees C);
      overall mean VAS (IM 43+/-9 OTM 39+/-1); onset (IM 35+/-32 and OTM 30+/-40min);
      offset (IM 96+/-56 and OTM 138+/-135min); duration (IM 61+/-47 OTM 99+/-124min).
      Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM
      administration of dexmedetomidine 40microg/kg produced similar overall sedative
      and antinociceptive effects.

PMID- 19577497
TI  - Feline herpesvirus 1 and feline calicivirus infections in a heterogeneous cat
      population of a rescue shelter.
AB  - Feline herpesvirus 1 (FeHV-1) and feline calicivirus (FCV), associated with upper
      respiratory tract disease, are highly prevalent in cats worldwide. With the aim
      to investigate the importance of feline respiratory viruses in a heterogeneous
      population of cats, samples were taken in a rescue shelter in Liege, Belgium,
      between March 2005 and August 2006. Reverse transcription polymerase chain
      reaction (RT-PCR) and polymerase chain reaction (PCR) were performed to diagnose
      FCV and FeHV-1 infection in the sampled cats. The prevalence rate (33.1%) was
      higher for FCV than for FeHV-1 (20.1%) whereas prevalence rate of co-infection
      with both viruses was 10%. Gingivitis was more common in FCV infections (odds
      ratio (OR)=2.83) whereas respiratory signs were more often observed with FeHV-1
      infections. The average age was significantly higher in FCV positive cats (38
      months) than in FeHV-1 positive cats (29.9 months). The second and the fourth
      quarters of the year and the two first quarters were significantly more at risk
      than the others in the case of FeHV-1 and FCV infection, respectively. Age was
      found to be a confounding factor. High prevalence of both infections strengthens
      the importance of applying hygienic and preventive measures in rescue shelters
      where cats with an unknown status of vaccination are introduced.

PMID- 19577500
TI  - [How I do... the management of fourth degree perineal injury following vaginal
      delivery?].

PMID- 19577501
TI  - [Cervical cancer screening: restoration or reconstruction?].

PMID- 19577499
TI  - [Feasibility of the sentinel node biopsy in breast cancer in case of histological
      multifocality diagnosis].
AB  - OBJECTIVES: The use of sentinel node biopsy (SNB) has replaced axillary lymph
      node dissection (ALND) as the new standard of care in early unifocal breast
      cancer. In multifocal breast cancer, this procedure remains controversial. The
      real problem is when a multifocal tumor is discovered during or after the
      surgery, with a SNB negative which has been already done. Should we do an
      additional ALND or not? PATIENTS AND METHODS: We performed a retrospective study
      of 43 multifocal breast cancer patients who underwent SNB. RESULTS: The mean
      histological primary tumor size was 16.8 mm (range, 1-52 mm). The mean number of
      SN removed was 2.07 (range, 1 to 5). Sixteen (34.1%) of the 43 patients had at
      least one positive SN. Twenty-seven patients had subsequent axillary dissection.
      Negative predictive value of SN procedure was 100% (95% confidence interval: 87.1
      100%) with a FN rate of 0%. Moreover, not any patient has developed axillary
      recurrence with a mean follow-up of 20.8 months (1-77). DISCUSSION AND
      CONCLUSION: Our data are not powerful enough to validate the SNB in multifocal
      breast tumor discovered after an initial surgery. However, the FN rate of 0% is
      encouraging and prospective studies with a systematic ALND can help surgeons to
      respond to the question.

PMID- 19577502
TI  - [Breast density: a major parameter to follow during hormone replacement therapy].
AB  - Mammographic density is a risk factor for breast cancer and it reflects
      variations in the tissue composition of the breast. It is notably influenced by
      body mass index and by endogenous hormones as well as hormone replacement therapy
      (HRT). The pathways that are responsible for the increase in mammographic density
      following exposure to hormones and those that increase risk of breast cancer are
      probably not the same. Careful clinical and mammographic follow-up is appropriate
      in women undergoing HRT because an increase in density is not only a risk factor
      for breast cancer but it also reduces screening sensitivity. We present a case in
      which mammographic density decreased after menopause, then dramatically increased
      after HRT and finally, surgical biopsy allowed the diagnosis of an infiltrative
      breast carcinoma. We discuss appropriate HRT changes in case of increasing
      mammographic density.

PMID- 19577503
TI  - Solvent free synthesis of 1,3-diaryl-2-propenones catalyzed by commercial acid
      clays under ultrasound irradiation.
AB  - This paper presents a novel solvent free method of synthesis of trans-chalcones.
      The method was based on ultrasound irradiation of the reagents (aryl methyl
      ketones and aryl aldehydes) in presence of commercial acid-montmorillonites as
      catalysts. The trans-chalcones were synthesized in high yields (85-95%) and
      excellent selectivity in a short reaction time.

PMID- 19577504
TI  - Validation of a numerical 3-D fluid-structure interaction model for a prosthetic
      valve based on experimental PIV measurements.
AB  - A numerical 3-D fluid-structure interaction (FSI) model of a prosthetic aortic
      valve was developed, based on a commercial computational fluid dynamics (CFD)
      software program using an Arbitrary Eulerian Lagrangian (ALE) formulation. To
      make sure of the validity of this numerical model, an equivalent experimental
      model accounting for both the geometrical features and the hydrodynamic
      conditions was also developed. The leaflet and the flow behaviours around the
      bileaflet valve were investigated numerically and experimentally by performing
      particle image velocimetry (PIV) measurements. Through quantitative and
      qualitative comparisons, it was shown that the leaflet behaviour and the velocity
      fields were similar in both models. The present study allows the validation of a
      fully coupled 3-D FSI numerical model. The promising numerical tool could be
      therefore used to investigate clinical issues involving the aortic valve.

PMID- 19577505
TI  - Geographic variability in geocoding success for West Nile virus cases in South
      Dakota.
AB  - Geocoding, the process of assigning each case a set of coordinates that closely
      approximates its true location, is an important component of spatial
      epidemiological studies. The failure to accurately geocode cases adversely
      affects the validity and strength of conclusions drawn from the analysis. We
      investigated whether there were differences among geographic locations and
      demographic classes in the ability to successfully geocode West Nile virus (WNV)
      cases in South Dakota. We successfully geocoded 1354 cases (80.8%) to their
      street address locations and assigned all 1676 cases to ZIP code tabulation areas
      (ZCTAs). Using spatial scan statistics, significant clusters of non-geocoded
      cases were identified in central and western South Dakota. Geocoding success
      rates were lower in areas of low population density and on Indian reservations
      than in other portions of the state. Geocoding success rates were lower for
      Native Americans than for other races. Spatial epidemiological studies should
      consider the potential biases that may result from excluding non-geocoded cases,
      particularly in rural portions of the Great Plains that contain large Native
      American populations.

PMID- 19577508
TI  - Fungal adaptation to the host environment.

PMID- 19577506
TI  - The validity and utility of classifying genes as 'essential'.

PMID- 19577509
TI  - Study of the luminescence properties of a novel rare earth complex
      Tb(DPC)(2)2H2O.
AB  - Rare earth complex Tb(DPC)(2)2H(2)O was synthesized by introducing Pyridine-2,6
      dicarboxylic acid(H(2)DPC) as the ligand and characterized by UV, fluorescent and
      infrared spectra as well as elemental analysis. The complex exhibited ligand
      sensitized green emission, and it has the higher sensitized luminescent
      efficiency and longer lifetime. The effect and mechanism of the ligand (H(2)DPC)
      on the luminescence properties of terbium complex was discussed. In device
      ITO/PVK/Tb(DPC)(2)2H(2)O/Al, Tb(3+) may be excited by intramolecular energy
      transfer from ligand as observed by electroluminescence. The main emitting peak
      at 545 nm can be attributed to the transition of (5)D(4)-->(7)F(5) of Tb(3+) ion
      and this process results in the enhancement of green emission from
      electroluminescence device.

PMID- 19577510
TI  - Infrared and infrared emission spectroscopy of gallium oxide alpha-GaO(OH)
      nanostructures.
AB  - Infrared spectroscopy has been used to study nano- to micro-sized gallium
      oxyhydroxide alpha-GaO(OH), prepared using a low temperature hydrothermal route.
      Rod-like alpha-GaO(OH) crystals with average length of approximately 2.5 microm
      and width of 1.5 microm were prepared when the initial molar ratio of Ga to OH
      was 1:3. beta-Ga(2)O(3) nano and micro-rods were prepared through the calcination
      of alpha-GaO(OH). The initial morphology of alpha-GaO(OH) is retained in the beta
      Ga(2)O(3) nanorods. The combination of infrared and infrared emission
      spectroscopy complimented with dynamic thermal analysis were used to characterise
      the alpha-GaO(OH) nanotubes and the formation of beta-Ga(2)O(3) nanorods. Bands
      at around 2903 and 2836 cm(-1) are assigned to the -OH stretching vibration of
      alpha-GaO(OH) nanorods. Infrared bands at around 952 and 1026 cm(-1) are assigned
      to the Ga-OH deformation modes of alpha-GaO(OH). A significant number of bands
      are observed in the 620-725 cm(-1) region and are assigned to GaO stretching
      vibrations.

PMID- 19577511
TI  - WITHDRAWN: Viral Hepatitis: global goals for vaccination.
AB  - This article has been withdrawn at the request of the author. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 19577512
TI  - Experimental study of a late response recorded from the thoracic wall after
      phrenic nerve stimulation.
AB  - OBJECTIVES: The phrenic nerve cervical stimulation induces an early motor
      diaphragmatic M response that may be recorded from the 7th ipsilateral
      intercostal space (ICS). Some responses with prolonged latency and of unclear
      origin can be recorded from the same recording site. The aim of the study was to
      determine the electrophysiological characteristics and the neuroanatomical
      pathways underlying the long-latency responses (LLRs) recorded from the 7th ICS.
      METHODS: We studied seven healthy volunteers, five patients with spinal cord
      injury and five patients with diaphragmatic palsy. All underwent phrenic nerve
      conduction study. An LLR was sought for at different stimulation sites using
      various stimulus intensities. RESULTS: A polyphasic LLR was recorded from the 7th
      ICS in all healthy subjects. It was mainly elicited by nociceptive stimulations,
      not only of the phrenic, but also of the median nerves. Its latency was longer
      than 70ms, with a wide inter- and intra-individual variability. Amplitude was
      highly variable and some habituation phenomenon occurred. The LLR was retained in
      most tetraplegic patients after phrenic nerve stimulation, but absent otherwise.
      It was present in all patients with diaphragmatic palsy after phrenic nerve
      stimulation. CONCLUSION: The LLR is likely to be produced by both intercostal and
      diaphragm muscles. It is a polysynaptic and multisegmental spinal response,
      probably conveyed by small-diameter nociceptive A-delta and/or C fibres and
      modulated by a supraspinal control. SIGNIFICANCE: The LLR recorded from the chest
      wall may constitute, by analogy with the nociceptive component of the lower limb
      flexion reflex in humans, a protective and withdrawal spinal reflex response.

PMID- 19577513
TI  - Sensorimotor processing in the grip-lift task: the impact of maximum wrist
      flexion/extension on force scaling.
AB  - OBJECTIVE: To evaluate the effect of wrist angulation on the grip force (GF)
      scaling in healthy subjects. METHODS: The first experiment investigated if
      hyperflexion or hyperextension of the wrist affects the scaling of GF. Subjects
      performed sets of 10 lifts with the wrist positioned in (i) a self-chosen,
      regular, slightly extended angulation, (ii) a hyperextended angulation and (iii)
      a hyperflexed angulation. The second experiment tested if wrist angulation
      applied during a preceding lift influenced GF scaling when lifting the object
      with a predefined wrist angulation. RESULTS: Compared with the regular and
      hyperflexed wrist angulations, subjects generated an overshoot of GF when lifting
      the object with the wrist hyperextended. Irrespective of the wrist angulation
      applied in the preceding lift, subjects generated an overshoot of GF when lifting
      the object with the wrist hyperextended, but not during lifts with the wrist in a
      regular or hyperflexed angulation. CONCLUSIONS: We demonstrate that a change in
      the horizontal angulation of the wrist of the grasping hand interferes with the
      scaling of GF. SIGNIFICANCE: We interpret these data to reflect a very basic
      strategic response of the motor system to changes in the geometry of the hand in
      order to ensure grasp stability.

PMID- 19577514
TI  - Characterising the slope of the distance-time relationship in swimming.
AB  - The aim of the present study was to assess whether the critical speed calculated
      by the slope of the distance-time relationship (S(d-t)) represents the boundary
      between the heavy and severe intensity domains in swimming and would be
      sustainable during intermittent exercise. Nine competitive male swimmers (mean+/
      SD: aged 21.2+/-2.6 yrs; peak (.)VO2 of 3866+/-529 mL min(-1)) performed, (a)
      four fixed-distance (100-200-400-800 m) all-out efforts to determine S(d-t) and
      peak (.)VO2; (b) three constant-speed efforts to exhaustion (TTE) at and 5% above
      and below S(d-t) (S(d-t)(+5%) and S(d-t)(-5%), respectively); (c) a set of 10 x
      400 m at S(d-t) with 40-s recovery in between. Capillary blood lactate
      concentration ([La](B)), oxygen uptake ((.)VO2), and RPE remained stable at S(d
      t)(-5%) (TTE=48.9+/-14.1 min) with end values of 3.8+/-1.9 mmol L(-1), 87+/-14%
      peak (.)VO2, and 4.7+/-1.3. TTE decreased at S(d-t)(+5%) (8.6+/-3.1 min), with
      end [La](B) of 10.2+/-1.9 mmol L(-1). Peak (.)VO2 was reached at exhaustion.
      Similarly, S(d-t) could only be maintained for 24.3+/-7.7 min with an increase in
      RPE and [La](B), (.)VO2 reaching its peak (95+/-5% peak VO2). RPE increased but
      [La](B) remained stable throughout the ten 400 m blocks performed at S(d-t)
      (overall time of 53.9+/-2.7 min). The physiological responses when swimming 5%
      below and 5% above S(d-t) are those characterising the heavy and severe intensity
      domain, respectively. While S(d-t) lies within the severe intensity domain,
      intermittent swims at this intensity induce [La](B) steady state alongside high
      rates of perceived exertion.

PMID- 19577515
TI  - Meeting the needs of young people with cancer: a lesson in change.

PMID- 19577516
TI  - Contrasting parental perspectives with those of teenagers and young adults with
      cancer: comparing the findings from two qualitative studies.
AB  - PURPOSE: To compare and contrast the issues raised in narrative data gathered
      from parents of teenagers and young adults with cancer with interview data
      gathered from young adults being treated for cancer. METHODS: A narrative
      correspondence method elicited contributions from the parents of 28 young adults
      with cancer. In-depth qualitative interviews were undertaken with 28 young adults
      in treatment for cancer or soon after their treatment. KEY RESULTS: The secondary
      analysis of the two data sets illuminates contrasting familial perspectives.
      While some of the topics raised by parents are also addressed by young people,
      their perspectives differ thus offering a 'mirror image' of the same issue. The
      contrast in priorities can contribute to stress within the family and can
      increase the danger of conflict over key decisions that may impact upon the
      health of the young adult with cancer. CONCLUSIONS: If the potential conflicts
      are anticipated and understood and as a consequence handled with skill by
      professionals in the setting of care, this can benefit family relationships which
      can be thrown into crisis by the illness. It is thus important that a model of
      care that incorporates such an understanding is widely implemented in order to
      mitigate the negative impact on family dynamics when cancer is diagnosed in young
      adulthood.

PMID- 19577517
TI  - Inflammation, cancer, and bone loss.
AB  - Skeletal distortions impose grave health disparities with potentially devastating
      consequences, including bone pain, immobility, and morbidity. Bone erosion is
      chiefly caused by hyperactive osteoclasts summoned to bone in response to
      circulating factors produced by tumor and inflammatory cells. Intense research in
      the past two decades has identified crucial elements and intricate circulatory
      systems that maintain and exacerbate inflammatory osteolysis. This progress led
      to better understanding of the mechanisms underlying this response and to
      developing advanced therapeutic interventions. Nevertheless, the multifactorial
      causes of inflammatory osteolysis continue to impose a great challenge for these
      therapies. This article provides an overview of some of the prominent facets
      contributing to this process.

PMID- 19577519
TI  - Implications of the Turing completeness of reaction-diffusion models, informed by
      GPGPU simulations on an XBox 360: cardiac arrhythmias, re-entry and the Halting
      problem.
AB  - In the arsenal of tools that a computational modeller can bring to bare on the
      study of cardiac arrhythmias, the most widely used and arguably the most
      successful is that of an excitable medium, a special case of a reaction-diffusion
      model. These are used to simulate the internal chemical reactions of a cardiac
      cell and the diffusion of their membrane voltages. Via a number of different
      methodologies it has previously been shown that reaction-diffusion systems are at
      multiple levels Turing complete. That is, they are capable of computation in the
      same manner as a universal Turing machine. However, all such computational
      systems are subject to a limitation known as the Halting problem. By constructing
      a universal logic gate using a cardiac cell model, we highlight how the Halting
      problem therefore could limit what it is possible to predict about cardiac
      tissue, arrhythmias and re-entry. All simulations for this work were carried out
      on the GPU of an XBox 360 development console, and we also highlight the great
      gains in computational power and efficiency produced by such general purpose
      processing on a GPU for cardiac simulations.

PMID- 19577518
TI  - The DosR regulon of M. tuberculosis and antibacterial tolerance.
AB  - Adaptation of Mycobacterium tuberculosis to an anaerobic dormant state that is
      tolerant to several antibacterials is mediated largely by a set of highly
      expressed genes controlled by DosR. A DosR mutant was constructed to investigate
      whether the DosR regulon is involved in antibacterial tolerance. We demonstrate
      that induction of the regulon is not required for drug tolerance either in vivo
      during a mouse infection or in vitro during anaerobic dormancy. Thus, drug
      tolerance observed in these models is due to other mechanisms such as the bacilli
      simply being in a non-replicating or low metabolic state. Our data also
      demonstrate that the DosR regulon is not essential for virulence during chronic
      murine infection. However, decreased lung pathology was observed in the DosR
      mutant. We also show that the DosR regulon genes are more highly conserved in
      environmental mycobacteria, than in pathogenic mycobacteria lacking a latent
      phase or environmental reservoir. It is possible that the DosR regulon could
      contribute to drug tolerance in human infections; however, it is not the only
      mechanism and not the primary mechanism for tolerance during a mouse infection.
      These data suggest that the regulon evolved not for pathogenesis or drug
      tolerance but for adaptation to anaerobic conditions in the environment and has
      been adapted by M. tuberculosis for survival during latent infection.

PMID- 19577520
TI  - Botulinum toxin type A for neurogenic detrusor overactivity due to spinal cord
      lesions in children: a retrospective study of seven cases.
AB  - OBJECTIVE: To assess the effectiveness and safety of intradetrusor injections of
      botulinum toxin type A (BTA) used to treat neurogenic detrusor overactivity in
      children. PATIENTS AND METHODS: We retrospectively reviewed the records of seven
      children treated at least once (7/7: one injection; 4/7: two and three
      injections; 2/7: four injections; 1/7: five injections) with intradetrusor BTA
      injections in 2005-2008, for neurogenic detrusor overactivity with incontinence
      despite timed bladder catheterizations and anticholinergic agents. Clinical,
      urodynamic, and imaging study data at baseline were collected. Clinical efficacy
      criteria were the urinary tract infection (UTI) rate, continence, and need for
      anticholinergic agents. The following urodynamic data were assessed: maximum
      catheterized volume without leakage, reflex volume, maximum detrusor pressure,
      and bladder compliance. RESULTS: Seven children received 18 injections. Social
      continence was achieved from the first injection. No further recurrent lower UTIs
      occurred. Maximum catheterized volume and reflex volume increased, and maximum
      detrusor pressure decreased. Detrusor compliance became interpretable and
      increased. Grade II right vesicoureteral reflux, present at baseline in one
      patient, resolved after BTA therapy. UTIs were the only adverse effects.
      CONCLUSION: Injection with BTA proved effective and safe in the short term. This
      may be an alternative to surgery in children with neurogenic detrusor
      overactivity.

PMID- 19577521
TI  - Immunization against angiotensins for the treatment of hypertension.
AB  - Current vaccination approaches against hypertension target angiotensin I and
      angiotensin II, key components of the renin-angiotensin system. The effectiveness
      and long-term safety of blockade of the renin-angiotensin system with
      antihypertensive small-molecule drugs is well documented. Phase I/II testing of
      the angiotensin I vaccine PMD3117 demonstrated safety and immunogenicity in
      humans. While angiotensin I-specific antibodies were induced blood pressure was
      not lowered, presumably due to insufficient antibody levels. A second vaccine,
      which targets angiotensin II, has been clinically tested. Administration of
      CYT006-AngQb to subjects with mild to moderate hypertension was safe and well
      tolerated. After three administrations of 300 microg of the vaccine, ambulatory
      blood pressure was significantly reduced compared to placebo. The vaccine was
      particularly effective early in the morning as systolic and diastolic blood
      pressure were lowered by -25 mm Hg and -13 mm Hg, respectively. Further studies
      are required to show long-term safety and to assess how robust and long-lived the
      blood pressure reduction is. It will also be important to ascertain whether the
      strong reduction of blood pressure in the early morning, when most cardiovascular
      events occur, might result in long-term benefits over current therapies.

PMID- 19577523
TI  - Quantitative analysis of mitragynine in human urine by high performance liquid
      chromatography-tandem mass spectrometry.
AB  - Mitragynine is the primary active alkaloid extracted from the leaves of Mitragyna
      speciosa Korth, a plant that originates in South-East Asia and is commonly known
      as kratom in Thailand. Kratom has been used for many centuries for their
      medicinal and psychoactive qualities, which are comparable to that of opiate
      based drugs. Kratom abuse can lead to a detectable content of mitragynine residue
      in urine. Ultra trace amount of mitragynine in human urine was determined by a
      high performance liquid chromatography coupled to an electrospray tandem mass
      spectrometry (HPLC-ESI/MS/MS). Mitragynine was extracted by methyl t-butyl ether
      (MTBE) and separated on a HILIC column. The ESI/MS/MS was accomplished using a
      triple quadrupole mass spectrometer in positive ion detection and multiple
      reactions monitoring (MRM) mode. Ajmalicine, a mitragynine's structure analog was
      selected as internal standard (IS) for method development. Quality control (QC)
      performed at three levels 0.1, 1 and 5 ng/ml of mitragynine in urine gave mean
      recoveries of 90, 109, and 98% with average relative standard deviation of 22, 12
      and 16%, respectively. The regression linearity of mitragynine calibration ranged
      from 0.01 to 5.0 ng/ml was achieved with correlation coefficient greater than
      0.995. A detection limit of 0.02 ng/ml and high precision data within-day and
      between days analysis were obtained.

PMID- 19577522
TI  - Quantitative LC-MS/MS method for the sensitive and simultaneous determination of
      natural hormones in bovine serum.
AB  - We have developed a liquid chromatography tandem mass spectrometric (LC-MS/MS)
      method for the simultaneous quantitative analysis of several free forms of
      steroid hormones in bovine serum [pregnenolone (P(5)), progesterone (P(4)),
      17hydroxyP(5), 17hydroxyP(4), testosterone (T), dehydroepiandrosterone (DHEA),
      androstenedione (A), estrone (E(1)), 2, 4 and 16 hydroxyE(1), 2 and 4
      methoxyE(1)]. Deuterated analogs were used as internal standards. Serum proteins
      were eliminated with acetonitrile. Oxime derivatives of steroids were extracted
      with tert-butylmethylether and analyzed in positive MRM mode. Methodology was
      validated in accordance with the European Commission Decision 2002/657/EC.
      Performance characteristics permit the use of this methodology for steroid
      determination in animal serum samples.

PMID- 19577524
TI  - Determination of the antifungal agent posaconazole in human serum by HPLC with
      parallel column-switching technique.
AB  - Posaconazole is a new broad-spectrum antifungal agent that is currently only
      available as an oral suspension and shows high intra- and inter-individual
      differences in oral bioavailibility. Pre-existing methods for the determination
      of the substance involve the use of internal standards or require a quite
      complicated and time-consuming sample pre-treatment. Our HPLC method is fast and
      fully-automated and there is no need for any manual sample pre-treatment. On-line
      transfer of posaconazole from the extraction column was followed by
      chromatographic separation on a C18 column and fluorescence detection
      (lambda(ex): 261 nm, lambda(em): 357 nm). Retention time of posaconazole was
      about 11.7 min, the lower limit of quantification was found to be 0.1 mg/l. A
      linear calibration curve was obtained over the concentration range of 0.1-5 mg/l
      using a 50 microl sample (r(2)=0.999). The relative standard deviations of intra
      day variations ranged from 2.3% to 9.4%, intra-day accuracy from 88.8% to 114.8%.

PMID- 19577525
TI  - Cost-effective plastic surgery skills training.

PMID- 19577526
TI  - One-stage vermilion switch flap procedure for the correction of thin lips in
      patients with bilateral cleft lips.
AB  - In this article, we describe the operative method for correction of thin lips in
      patients with bilateral cleft lips. Two transverse triangular flaps were designed
      in the lower vermilion and elevated along with the labial arteries and the
      surrounding tissues. These flaps were inserted into the recipient site on the
      upper vermilion through the subcutaneous tunnels at the oral commissure through a
      one-stage process; the donor site was closed directly. Two patients with
      bilateral cleft lip underwent this operation for thin lips, and satisfying
      results with less morbidity were obtained. The upper lip retained its volume
      postoperatively, and the donor-site scar was inconspicuous. Our method enabled
      both the augmentation of the upper vermilion and the reduction of the lower
      vermilion in a one-stage procedure.

PMID- 19577527
TI  - Craniofacial reconstruction with bone and biomaterials: review over the last 11
      years.
AB  - This review aims to compare bone grafts and different biomaterials for
      reconstruction of craniofacial bones in congenital defects, after trauma, and
      after tumour surgery. A Pubmed search was performed and publications over the
      last 11 years describing reconstructions of craniofacial bones in non-load
      bearing areas were reviewed. Only human studies using bone grafts and
      biomaterials were included. Studies on skull base reconstruction, distraction
      osteogenesis, free and pedicled bone flaps and bone-anchored epithesis were
      excluded. Out of 83 studies, three were prospective, 65 retrospective and 15
      studies were case reports. There were seven comparative studies found and some
      efforts on statistical analysis were made. Except for a few studies, the
      statistical significant differences in outcomes were found to be related to size
      and location of bone defects rather than reconstruction method and biomaterial
      used. An increasing number of alloplastic materials have been available as
      alternatives to the gold standard autologous bone transplantation for
      craniofacial bone repair. Comparative studies with statistical analyses on
      differences in success rates between different biomaterials or bone grafts for
      specific indications are needed.

PMID- 19577529
TI  - Heterotopic ossification of a temporal fascial flap pedicle in ear
      reconstruction.

PMID- 19577528
TI  - Macrovascular arteriovenous shunts (MAS): a newly identified structure in the
      abdominal wall with implications for thermoregulation and free tissue transfer.
AB  - Microscopic arteriovenous anastomoses are known structures that have many
      clinical implications, with disease states such as Reynaud's phenomenon and
      erythromelalgia known consequences of their abnormal functioning. These pre
      capillary arteriovenous communications result in increased regional blood flow at
      the time of capillary filling. Recent advances in imaging technology, providing
      physiological and anatomical data, have identified a previously undescribed
      anatomical structure, that of large-vessel (macroscopic) arteriovenous
      communications, with profoundly different implications. Computed tomographic
      angiography (CTA) of the abdominal wall vasculature was undertaken in 140
      patients prior to reconstructive surgery. All scans were arterial phase,
      demonstrating functional arteriovenous communications in all patients. These
      communications identified vascular shunting occurring prior to capillary filling.
      Fine-cut slices were able to visualise the structures, demonstrate their size as
      macroscopic (>1 mm diameter) and map the course of the arteriovenous
      communications. The potential clinical implications and therapeutic possibilities
      in a range of medical and surgical conditions are described.

PMID- 19577530
TI  - Declarations, declarations.

PMID- 19577531
TI  - Genetic variability in geographical populations of Culex quinquefasciatus Say
      (Diptera: Culicidae) from India based on random amplified polymorphic DNA
      analysis.
AB  - Genetic variability and environmental factors may influence the refractiveness,
      propagation of pathogen and transmission of disease. Random amplified polymorphic
      DNA (RAPD) is one of the widely used molecular markers for population genetic
      diversity studies. In present study, RAPD is used to ascertain the genetic
      variability in Culex quinquefasciatus populations collected from various Indian
      geographical locations. Out of 50 RAPD primers screened, 14 primers exhibited
      clear, concrete and distinct banding pattern showing up to 100% polymorphism.
      Primer OPBD3 was tested with DNA of 14 geographical populations from India
      (including one laboratory population) showed 21 loci representing 14 populations
      with 100% polymorphism. The genetic diversity among the populations indicated the
      Shannon index (I) and gene diversity index (H(ST)), 0.48 and 0.31, respectively
      among the population, displaying rich genetic variation among the Cx.
      quinquefasciatus populations. Consensus tree showed two clusters indicating the
      genetic variation among the various geographical populations. The findings of
      this study may be useful to understand the population variation under different
      ecological conditions and development of effective vector management strategies.

PMID- 19577532
TI  - Socio-environmental conditions, intestinal parasitic infections and nutritional
      status in children from a suburban neighborhood of La Plata, Argentina.
AB  - We analyzed intestinal parasitic infections in children aged 1-12 years from a
      poor neighborhood in La Plata, Argentina, and determined the correlations with
      their nutritional status and socio-environmental conditions. We performed
      parasitological analyses with anal brushed technique (for Enterobius vermicularis
      eggs) and fecal samples, employing the techniques of Ritchie, Carles Barthelemy
      and Willis. The worm burdens of nematodes were estimated by means of Kato Katz
      technique. Low weight-for-age (underweight), height-for-age (stunting) and weight
      for-height (wasting) were calculated based on the 5th centile of the WHO 2006
      (children under 5) and CDC 2000 (older children and adolescents) growth
      references. We also analyzed samples of soil, water, and canine feces and
      surveyed other domestic and environmental data using structured questionnaires to
      each child's parents. To associate the parasitological, anthropometric and socio
      environmental data, a categorical analysis of principal components (catPCA) was
      conducted. In the first axis of catPCA, the correlations among socio
      environmental variables showed a gradient of "relative welfare". The eigenvectors
      showed the most influential variables in the analysis were promiscuity (0.0765),
      father's education (-0.741), crowding (0.727), wastewater disposal (-0.658),
      mother's education (-0.574), and flooding (-0.409). The 85% of children were
      parasitized and 79.6% polyparasitized. The 27.7% of children had deficit in some
      nutritional status indicator, being the stunting the most prevalent deficit
      (16.8%). There also found parasites in 42% of the dog feces, 53% of the soil
      samples, and non-pathogenic amoebae in the water samples. The SEV was mainly
      associated with geohelminths and stunting, especially among the poorest children.
      The study evidences that living conditions are variable within this population.
      Part of these variations could be linked to the differences in the extent to
      which parents are able to use their scant resources to influence their children's
      morbidity. Further studies need to be done from a qualitative approach.

PMID- 19577533
TI  - Identification of Nile red as a fluorescent substrate of the Candida albicans ATP
      binding cassette transporters Cdr1p and Cdr2p and the major facilitator
      superfamily transporter Mdr1p.
AB  - Clinically relevant azole resistance in the fungal pathogen Candida albicans is
      most often associated with the increased expression of plasma membrane efflux
      pumps, specifically the ATP-binding cassette (ABC) transporters CaCdr1p and
      CaCdr2p and the major facilitator superfamily (MFS) transporter CaMdr1p.
      Development of potent pump inhibitors that chemosensitize cells to azoles is a
      promising approach to overcome antifungal resistance. Here we identify Nile red
      as a new fluorescent substrate for CaCdr1p, CaCdr2p, and CaMdr1p. Nile red was
      effluxed efficiently from Saccharomyces cerevisiae cells heterologously
      expressing these transporters. Enniatin selectively inhibited the efflux of Nile
      red from S. cerevisiae cells expressing CaCdr1p or CaMdr1p but not from cells
      expressing CaCdr2p. This indicates that Nile red can be used for the
      identification of inhibitors specific for particular transporters mediating
      antifungal resistance in pathogenic yeast.

PMID- 19577534
TI  - Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in
      oxidative catalysis.
AB  - Nitronate monooxygenase (NMO), formerly referred to as 2-nitropropane
      dioxygenase, is an FMN-dependent enzyme that uses molecular oxygen to oxidize
      (anionic) alkyl nitronates and, in the case of the enzyme from Neurospora crassa,
      (neutral) nitroalkanes to the corresponding carbonyl compounds and nitrite. Over
      the past 5 years, a resurgence of interest on the enzymology of NMO has driven
      several studies aimed at the elucidation of the mechanistic and structural
      properties of the enzyme. This review article summarizes the knowledge gained
      from these studies on NMO, which has been emerging as a model system for the
      investigation of anionic flavosemiquinone intermediates in the oxidative
      catalysis of organic molecules, and for the effect that branching of reaction
      intermediates has on both the kinetic parameters and isotope effects associated
      with enzymatic reactions. A comparison of the catalytic mechanism of NMO with
      other flavin-dependent enzymes that oxidize nitroalkane and nitronates is also
      presented.

PMID- 19577535
TI  - Localization of cytochrome b6f complexes implies an incomplete respiratory chain
      in cytoplasmic membranes of the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The cytochrome b(6)f complex is an integral part of the photosynthetic and
      respiratory electron transfer chain of oxygenic photosynthetic bacteria. The core
      of this complex is composed of four subunits, cytochrome b, cytochrome f, subunit
      IV and the Rieske protein (PetC). In this study deletion mutants of all three
      petC genes of Synechocystis sp. PCC 6803 were constructed to investigate their
      localization, involvement in electron transfer, respiration and photohydrogen
      evolution. Immunoblots revealed that PetC1, PetC2, and all other core subunits
      were exclusively localized in the thylakoids, while the third Rieske protein
      (PetC3) was the only subunit found in the cytoplasmic membrane. Deletion of petC3
      and both of the quinol oxidases failed to elicit a change in respiration rate,
      when compared to the respective oxidase mutant. This supports a different
      function of PetC3 other than respiratory electron transfer. We conclude that the
      cytoplasmic membrane of Synechocystis lacks both a cytochrome c oxidase and the
      cytochrome b(6)f complex and present a model for the major electron transfer
      pathways in the two membranes of Synechocystis. In this model there is no proton
      pumping electron transfer complex in the cytoplasmic membrane. Cyclic electron
      transfer was impaired in all petC1 mutants. Nonetheless, hydrogenase activity and
      photohydrogen evolution of all mutants were similar to wild type cells. A reduced
      linear electron transfer and an increased quinol oxidase activity seem to
      counteract an increased hydrogen evolution in this case. This adds further
      support to the close interplay between the cytochrome bd oxidase and the
      bidirectional hydrogenase.

PMID- 19577537
TI  - Prediction of efficacy of anti-TNF biologic agent, infliximab, for rheumatoid
      arthritis patients using a comprehensive transcriptome analysis of white blood
      cells.
AB  - Introduction of biologics, such as infliximab, to the therapy of rheumatoid
      arthritis (RA) patients has revolutionized the treatment of this disease.
      However, biomarkers for predicting the efficacy of the drug at an early phase of
      treatment for selecting real responders have not been found. We here present
      predictive markers based on a thorough transcriptome analysis of white blood
      cells from RA patients. RNA from whole blood cells of consecutive 42 patients
      before the first infusion was analyzed with microarrays for training studies.
      Samples from the subsequent 26 consecutive patients were used for a prospective
      study. We categorized the results into no inflammation and residual inflammation
      groups using the serum C-reactive protein (CRP) level at 14weeks after the first
      infusion. The accuracy of prediction in our study was 65.4%.

PMID- 19577536
TI  - Restoration of cyclin D2 has an inhibitory potential on the proliferation of
      LNCaP cells.
AB  - Despite well known oncogenic function of G1-S cell-cycle progression, cyclin D2
      (CCND2) is often silenced epigenetically in prostate cancers. Here we show that
      CCND2 has an inhibitory potential on the proliferation of androgen receptor (AR)
      dependent prostate cancer LNCaP cells. Forced expression of CCND2 suppressed the
      proliferative ability and induced cell death in LNCaP cells in a cdk-independent
      manner. Knocking down CCND2 restored the proliferation of LNCaP subclones with
      relatively high CCND2 expression and low proliferative profiles.
      Immunoprecipitation using deletion mutants of CCND2 indicated that a central
      domain of CCND2 is required for binding to AR. A deletion mutant lacking the
      central domain failed to hinder LNCaP cells. Collectively, our results indicated
      that CCND2 inhibits cell proliferation of AR-dependent prostate cancer through
      the interaction with AR. Our study suggests that restoration of CCND2 expression
      potentially prevents the carcinogenesis of prostate cancer, which is mostly AR
      dependent in the initial settings.

PMID- 19577538
TI  - Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA
      fragmentation factor-alpha-like effector A, in rat interscapular brown adipose
      tissue by sympathetically activated beta3-adrenoreceptors.
AB  - The thermogenic activity of brown adipose tissue (BAT) largely depends on the
      mitochondrial uncoupling protein 1 (UCP1), which is up-regulated by environmental
      alterations such as cold. Recently, CIDEA (cell death-inducing DNA fragmentation
      factor-alpha-like effector A) has also been shown to be expressed at high levels
      in the mitochondria of BAT. Here we examined the effect of cold on the mRNA and
      protein levels of CIDEA in interscapular BAT of conscious rats with regard to the
      sympathetic nervous system. Cold exposure (4 degrees C for 3h) elevated the
      plasma norepinephrine level and increased norepinephrine turnover in BAT. Cold
      exposure resulted in down-regulation of the mRNA and protein levels of CIDEA in
      BAT, accompanied by up-regulation of mRNA and protein levels of UCP1. The cold
      exposure-induced changes of CIDEA and UCP1 were attenuated by intraperitoneal
      pretreatment with propranolol (a non-selective beta-adrenoreceptor antagonist)
      (2mg/animal) or SR59230A (a selective beta(3)-adrenoreceptor antagonist)
      (2mg/animal), respectively. These results suggest that acute cold exposure
      resulted in down-regulation of CIDEA in interscapular BAT by sympathetically
      activated beta(3)-adrenoreceptor-mediated mechanisms in rats.

PMID- 19577539
TI  - Black shank resistant tobacco by silencing of glutathione S-transferase.
AB  - A glutathione S-transferase gene was amplified from cDNA of Nicotiana tabacum
      roots infected with Phytophthora parasitica var. nicotianae. The gene was cloned
      in sense and anti-sense orientation to an RNAi vector for induced gene silencing,
      and reduced expression of the gene was detected by RT-PCR. A statistically
      significant increase in resistance of N. tabacum to infection following gene
      silencing was found for glutathione S-transferase-silenced plants compared with
      control plants. Some defense genes were up-regulated in glutathione S-transferase
      silenced plants during the interaction with the pathogen. This is the first
      evidence of the role of glutathione S-transferase as negative regulator of
      defense response.

PMID- 19577540
TI  - Protein splicing of the three Pyrococcus abyssi ribonucleotide reductase inteins.
AB  - An intein is a polypeptide that interrupts the functional domains of a protein,
      called the exteins. The intein can facilitate its own excision from the exteins,
      concomitant with the ligation of the exteins, in a process called protein
      splicing. The alpha subunit of the ribonucleotide reductase of the extreme
      thermophile Pyrococcus abyssi is interrupted by three inteins in separate
      insertion sites. Each intein can facilitate protein splicing when over-expressed
      in Escherichia coli, with affinity domains serving as the exteins. The influence
      of the N-terminal flanking residue on the efficiency of splicing is specific to
      each intein. Each intein has a different downstream nucleophilic residue, and
      cannot tolerate substitution to a residue of lesser or equal nucleophilicity. The
      influence of the conserved penultimate His also differs between the inteins.

PMID- 19577541
TI  - Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta
      catenin dependent Wnt signaling pathway together with Wnt5a.
AB  - Correct Wnt signaling is required for adipogenesis and alterations occur in Type
      2 diabetes mellitus (T2DM). Gene expression studies showed that beta-catenin
      independent Wnt5b was down-regulated in T2DM preadipocytes, while its paralog
      Wnt5a was unchanged. Our study aimed at defining the expression profile and
      function of Wnt5a and Wnt5b during adipogenesis by determining their effect on
      aP2 and PPARgamma expression and assessing the level of beta-catenin
      translocation in mouse 3T3-L1 preadipocytes. Additionally, we explored the effect
      on adipogenic capacity by Wnt5b overexpression in combination with stimulation of
      the beta-catenin dependent or beta-catenin independent Wnt signaling. Expression
      of Wnt5b was, like Wnt5a, down-regulated upon induction of differentiation and
      both inhibit beta-catenin dependent Wnt signaling at the initiation of
      adipogenesis. Wnt5b additionally appears to be a potent enhancer of adipogenic
      capacity by stimulation of PPARgamma and aP2. Down-regulation of Wnt5b could
      therefore contribute to decreased adipogenesis observed in T2DM diabetic
      subjects.

PMID- 19577542
TI  - Mechanosensitive promoter region in the human HB-GAM gene.
AB  - Mechanical loading is essential for maintaining bone mass in the adult skeleton.
      However, the underlying process of the transfer of the physical stimulus into a
      biochemical response, which is termed mechanotransduction is poorly understood.
      Mechanotransduction results in the modulation of gene expression through specific
      transcription factor binding sites in the promoter region of mechanosensitive
      genes. In the present study, we demonstrate that the expression of HB-GAM, which
      is known to have stimulating effects on osteogenic differentiation, is rapidly
      induced by mechanical loading in hMSC-TERT4 cells. Analysis of the human HB-GAM
      gene upstream regulatory region with luciferase reporter gene assays revealed
      that the upregulation of HB-GAM expression occurred at the transcriptional level
      and was mainly dependent on the HB-GAM promoter region most upstream containing
      three potential AP-1 binding motifs.

PMID- 19577543
TI  - CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects
      with TNF-alpha.
AB  - Our previous data show that CKLF-like MARVEL transmembrane domain-containing
      member 5 (CMTM5) is a potential tumor suppressor gene, but its function in
      pancreatic cancer is unknown. Herein we first report that CMTM5 is also absent in
      pancreatic cancer cell lines with promoter methylation. Compared with normal
      pancreatic tissues, CMTM5 is significantly decreased in cancer tissues.
      Restoration of CMTM5-v1 not only induces MIA PaCa-2 cell apoptosis with
      activation of caspase 3, 8 and 9, but also has synergistic effects with TNF
      alpha. Thus, CMTM5 may play a role in the pancreatic cancer.

PMID- 19577544
TI  - Immuno-PCR assays for immunogenicity testing.
AB  - The administration of therapeutic proteins often induces immunogenic response and
      thus formation of anti-drug antibodies (ADA), which can neutralize the drug's
      therapeutic effect and may even cause serious health problems. We here report on
      the employment of the ultra-sensitive immuno-PCR (IPCR) method to facilitate
      immunogenicity testing using two established assay formats. In a "bridging
      assay", in which ADA forms a bridge to immobilize a signal-generating drug
      reporter probe, IPCR detection enabled an at least 1000-fold increase in
      sensitivity, as compared to the analogous ELISA, along with a high drug tolerance
      value. Moreover, we demonstrate that interfering effects of the biological matrix
      can be omitted by a simple dilution of analytical samples without loss in assay
      performance. In a cell-free "neutralizing assay", in which a labeled drug
      reporter probe competes for binding to either surface-bound receptors or
      neutralizing ADA, the IPCR assay also revealed high sensitivity. These results
      suggest that IPCR has the potential to become a standard methodology in
      immunogenicity testing.

PMID- 19577545
TI  - A reversible model of the cognitive impairment associated with schizophrenia in
      monkeys: potential therapeutic effects of two nicotinic acetylcholine receptor
      agonists.
AB  - In monkeys proficient in the performance of a computer-assisted delayed response
      task, administration of sub-sedative doses of ketamine significantly impaired
      task performance after the 2mg/kg dose, producing a decrease in accuracies across
      all four delay intervals. Ketamine elicited occasional and inconsistent increases
      in task latencies. But in general processing speed was not dramatically affected
      by the test dose. Pretreatment with the alpha7 nicotinic receptor agonist GTS-21
      (DMXB-A) [3-[(3E)-3-[(2,4-dimethoxyphenyl) methylidene]-5,6-dihydro-4H-pyridin-2
      yl]pyridine] produced a dose-dependent attenuation of ketamine-induced decreases
      in task accuracies. In fact, the best dose of GTS-21 completely reversed the
      effects of ketamine. The nicotine metabolite cotinine is a cognitive-enhancer,
      and active in models predictive of antipsychotic activity. Pretreatment with
      cotinine did not reverse the task deficits produced by ketamine, and selection of
      a best dose was necessary to show the activity of cotinine. However, the best
      dose of cotinine, like GTS-21, completely reversed the ketamine-induced task
      deficits. Task accuracies were increased relative to their non-ketamine baselines
      during sessions run 24h later. The cotinine-ketamine order of administration was
      reversed to provide a more clinically relevant model, and cotinine post-treatment
      regimen produced a clear reversal of the ketamine-induced task deficits. The
      protracted task improvement also was still evident. The DMTS task impairment
      induced by ketamine was capable of being completely reversed by two compounds
      that are known to improve working memory and cognition. The model could provide a
      means of late stage preclinical evaluation of new compounds that address the
      cognitive impairment associated with major psychotic disease.

PMID- 19577547
TI  - Neural correlates of dual-task effect on belief-bias syllogistic reasoning: a
      near-infrared spectroscopy study.
AB  - Recent dual-process reasoning theories have explained the belief-bias effect, the
      tendency for human reasoning to be erroneously biased when logical conclusions
      are incongruent with beliefs about the world, by proposing a belief-based
      automatic heuristic system and logic-based demanding analytic system. Although
      these claims are supported by the behavioral finding that high-load secondary
      tasks enhance the belief-bias effect, the neural correlates of dual-task
      reasoning remain unknown. The present study therefore examined the relationship
      between dual-task effect and activity in the inferior frontal cortex (IFC) during
      belief-bias reasoning by near-infrared spectroscopy (NIRS). Forty-eight subjects
      participated in this study (MA=23.46 years). They were required to perform
      congruent and incongruent reasoning trials while responding to high- and low-load
      secondary tasks. Behavioral analysis showed that the high-load secondary task
      impaired only incongruent reasoning performance. NIRS analysis found that the
      high-load secondary task decreased right IFC activity during incongruent trials.
      Correlation analysis showed that subjects with enhanced right IFC activity could
      perform better in the incongruent reasoning trials, though subjects for whom
      right IFC activity was impaired by the secondary task could not maintain better
      reasoning performance. These findings suggest that the right IFC may be
      responsible for the dual-task effect in conflicting reasoning processes. When
      secondary tasks impair right IFC activity, subjects may rely on the automatic
      heuristic system, which results in belief-bias responses. We therefore offer the
      first demonstration of neural correlates of dual-task effect on IFC activity in
      belief-bias reasoning.

PMID- 19577546
TI  - The roles of sex and serotonin transporter levels in age- and stress-related
      emotionality in mice.
AB  - Mood disorders are influenced by genetic make-up and differentially affect men
      and women. The s/l promoter polymorphism in the serotonin transporter (SERT) gene
      moderates both trait emotion and the vulnerability to develop depressive states
      in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated
      emotionality phenotype. We now report that the SERT-KO phenotype is maintained
      throughout late-adulthood, and that female KO mice develop a larger emotionality
      phenotype with increasing age. Thus, to test the hypothesis that these findings
      reflected a putative sexual dimorphism in SERT-mediated modulation of
      emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and
      KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral
      changes. In males, the elevated SERT-KO emotion-related behavior converged with
      other groups after UCMS. Conversely, female SERT-KO displayed a normal non
      stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed
      variable and intermediate phenotypes in both experiments. Thus, consistent
      results across different biological modalities (age, stress) revealed a high
      contribution of SERT genotype for baseline "trait" emotionality in males, and low
      contribution for females. In contrast, age-correlated and stress-induced
      behavioral changes resulted in a high SERT genotype-mediated behavioral variance
      in females, but low in males. This suggests that high emotionality states
      associated with low SERT were differentially achieved in males (high
      baseline/trait) compared to females (increased vulnerability to develop high
      emotionality). This sex-by-SERT double dissociation provides a framework to
      investigate molecular substrates of emotionality regulation in concert with
      serotonin function and may contribute to the sexually dimorphic features of mood
      disorders.

PMID- 19577548
TI  - Histological studies of the effects of chronic implantation of ceramic-based
      microelectrode arrays and microdialysis probes in rat prefrontal cortex.
AB  - Chronic implantation of neurotransmitter measuring devices is essential for
      awake, behavioral studies occurring over multiple days. Little is known regarding
      the effects of long term implantation on surrounding brain parenchyma and the
      resulting alterations in the functional properties of this tissue. We examined
      the extent of tissue damage produced by chronic implantation of either ceramic
      microelectrode arrays (MEAs) or microdialysis probes. Histological studies were
      carried out on fixed tissues using stains for neurons (cresyl violet), astrocytes
      (GFAP), microglia (Iba1), glutamatergic nerve fibers (VGLUT1), and the blood
      brain barrier (SMI-71). Nissl staining showed pronounced tissue body loss with
      microdialysis implants compared to MEAs. The MEAs produced mild gliosis extending
      50-100 microm from the tracks, with a significant change in the affected areas
      starting at 3 days. By contrast, the microdialysis probes produced gliosis
      extending 200-300 microm from the track, which was significant at 3 and 7 days.
      Markers for microglia and glutamatergic fibers supported that the MEAs produce
      minimal damage with significant changes occurring only at 3 and 7 days that
      return to control levels by 1 month. SMI-71 staining supported the integrity of
      the blood-brain barrier out to 1 week for both the microdialysis probes and the
      MEAs. This data support that the ceramic MEA's small size and biocompatibility
      are necessary to accurately measure neurotransmitter levels in the intact brain.
      The minimal invasiveness of the MEAs reduce tissue loss, allowing for long term
      (>6 month) electrochemical and electrophysiological monitoring of brain activity.

PMID- 19577551
TI  - Brain networks of bottom-up triggered and top-down controlled shifting of
      auditory attention.
AB  - During functional magnetic resonance imaging (fMRI), our participants selectively
      attended to tone streams at the left or right, and occasionally shifted their
      attention from one stream to another as guided by a centrally presented visual
      cue. Duration changes in the to-be-attended stream served as targets. Loudness
      deviating tones (LDTs) occurred infrequently in both streams to catch attention
      in a bottom-up manner, as indicated by their effects on reaction times to
      targets. LDTs activated the right temporo-parietal junction (TPJ), posterior
      parts of the left inferior/middle frontal gyrus (IFG/MFG), ventromedial parts of
      the superior parietal lobule (SPL), and left frontal eye field/premotor cortex
      (FEF/PMC). In addition, LDTs in the to-be-ignored sound stream were associated
      with enhanced activity in the ventromedial prefrontal cortex (VMPFC) possibly
      related to evaluation of the distracting event. Top-down controlled cue-guided
      attention shifts (CASs) activated bilateral areas in the SPL, intraparietal
      sulcus (IPS), FEF/PMC, TPJ, IFG/MFG, and cingulate/medial frontal gyrus, and crus
      I/II of the cerebellum. Thus, our results suggest that in audition top-down
      controlled and bottom-up triggered shifting of attention activate largely
      overlapping temporo-parietal, superior parietal and frontal areas. As the IPS,
      superior parts of the SPL, and crus I/II were activated specifically by top-down
      controlled attention shifts, and the VMPFC was specifically activated by bottom
      up triggered attention shifts, our results also suggest some differences between
      auditory top-down controlled and bottom-up triggered shifting of attention.

PMID- 19577550
TI  - Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-3 through
      NFkB and MAPK dependent pathways in rat astrocytes [corrected].
AB  - The chemokines CCL2 and CCL7 are upregulated in the brain during several
      neurodegenerative and acute diseases associated with infiltration of peripheral
      leukocytes. Astrocytes can respond to inflammatory cytokines like IL-1beta and
      TNF-alpha by producing chemokines. This study aims to test the ability of IL
      1beta and TNF-alpha to stimulate CCL2 and CCL7 protein production in rat
      astrocyte cultures, and to elucidate signaling pathways involved in the cytokine
      stimulated chemokine upregulation. Astrocytes were stimulated with IL-1beta or
      TNF-alpha, and CCL2 and CCL7 levels determined by ELISA. Our results show that IL
      1beta and TNF-alpha each stimulate production of the chemokines CCL2 and CCL7 in
      astrocytes in a concentration- and time-dependent manner, with CCL2 showing a
      more rapid and robust response to the cytokine treatment than CCL7. As a first
      step to determine the signaling pathways involved in CCL2 and CCL7 upregulation,
      we stimulated astrocytes with IL-1beta or TNF-alpha in the presence of selective
      inhibitors of MAPK pathways (SB203580 and SB202190 for p38, SP600125 for JNK, and
      U0126 for ERK) or NFkappaB pathways (MG-132 and SC-514). We found that NFkappaB
      pathways are important for the cytokine-stimulated CCL2 and CCL7 production,
      whereas MAPK pathways involving p38 and JNK, but not ERK, may also contribute but
      to a lesser extent. These data document for the first time that CCL7 protein
      production can be stimulated in astrocytes by cytokines, and that the
      upregulation may involve NFkappaB- and p38/JNK-regulated pathways. In addition,
      our results suggest that CCL2 and CCL7 share similarities in the signaling
      pathways necessary for their upregulation.

PMID- 19577552
TI  - Gallic acid ester derivatives induce apoptosis and cell adhesion inhibition in
      melanoma cells: The relationship between free radical generation, glutathione
      depletion and cell death.
AB  - Malignant melanoma is a lethal disease, and the incidence and mortality
      associated with it are increasing worldwide. It has a significant tendency to
      develop both metastasis and resistance to chemotherapy. The tumor cells show
      abnormal redox regulation, and although the molecular mechanisms involved are not
      well characterized, they seem to be related to oxidative stress. In a previous
      study, we showed the antitumoral properties of gallic acid ester derivatives in
      leukemia cells. Here, we show the effect of octyl, decyl, dodecyl and tetradecyl
      gallates on B16F10 cells, a melanoma cell line. All compounds induced cytotoxic
      effects, and the IC(50) values obtained were between 7microM and 17microM after
      48h of incubation. Cell death occurred through apoptosis, as demonstrated by the
      genomic DNA fragmentation pattern. The gallates were able to induce significant
      production of free radicals, deplete both glutathione and ATP, activate NF-kappaB
      and promote the inhibition of cell adhesion under the experimental conditions.
      The glutathione depletion induced by these compounds was related to the
      inhibition of gamma-glutamylcysteine synthase activity. These results suggest
      that gallates induce tumoral cell death through apoptosis as a consequence of
      oxidative stress, though they use different mechanisms to do so. These findings
      are important since melanoma cells are resistant to death because of their high
      level of antioxidant defense, adhesion capability and propensity to metastasize.

PMID- 19577553
TI  - Sodium arsenite-induced DAPK promoter hypermethylation and autophagy via ERK1/2
      phosphorylation in human uroepithelial cells.
AB  - Arsenic compounds or arsenicals are well-known toxic and carcinogenic agents. The
      toxic effects of arsenic that are of most concern to humans are those that occur
      from chronic, low-level exposure, and are associated with various human
      malignancies, including skin, lung and bladder cancers. In addition, arsenic
      could induce cell death, including apoptosis or autophagy in malignant cells.
      Previously, we have demonstrated that arsenite can induce autophagy and death
      associated protein kinase (DAPK) promoter hypermethylation in the SV-40
      immortalized human uroepithelial cell line (SV-HUC-1). However, the underlying
      mechanism of arsenite-induced autophagy is still unclear. In the present study,
      we demonstrate that arsenite can activate the extracellular signaling-regulated
      protein kinase 1/2 (ERK1/2) signaling pathway after treatment in SV-HUC-1 cells
      by using immunocytochemistry and Western blotting. In addition, our results also
      show an increase of autophagosomes was produced in arsenite-treated SV-HUC-1
      cells by using electron microscopy. We found that, by incrementally increasing
      the dosages, microtubule-associated protein light chain 3B (LC3B) and Beclin-1
      are important regulators for the formation of autophagosomes, in a dose-dependent
      manner. When the cells were pretreated with inhibitors 5-aza-CdR or U0126 for
      24h, the effect of arsenite on ERK1/2, LC3B, Beclin-1 and DAPK proteins
      expression is suppressed. Furthermore, our results support the notion that
      arsenite can induce the ERK1/2 signaling pathway to stimulate autophagy and DAPK
      promoter hypermethylation in human uroepithelial SV-HUC-1 cells. These findings
      may contribute to a better understanding of the carcinogenesis of arsenite.

PMID- 19577549
TI  - Glucocorticoid status affects antidepressant regulation of locus coeruleus
      tyrosine hydroxylase and dorsal raphe tryptophan hydroxylase gene expression.
AB  - Brainstem monoaminergic nuclei express glucocorticoid receptors (GR), and
      glucocorticoids have been shown to inhibit expression of enzymes involved in
      monoamine synthesis. Monoamine deficits have been implicated in depression
      pathology. However, it is unknown if antidepressants regulate brainstem GR, and
      if glucocorticoids might influence antidepressant effects on monoamine
      synthesizing enzymes. Our lab has found opposing effects of the monoamine oxidase
      inhibitor phenelzine and the tricyclic antidepressant imipramine on HPA activity
      and forebrain GR gene expression. We therefore hypothesized that phenelzine and
      imipramine would also affect brainstem GR gene expression differentially, and
      that antidepressant-induced changes in GR expression would correlate with effects
      on monoamine-synthesizing enzyme expression. Using in situ hybridization, we
      measured effects of chronic antidepressant treatment on brainstem GR, locus
      coeruleus and ventral tegmental area (VTA) tyrosine hydroxylase (TH), and dorsal
      raphe tryptophan hydroxylase (TPH2) gene expression in male C57BL/6 mice that
      were adrenalectomized and replaced with defined levels of corticosterone. GR
      expression was decreased by phenelzine in the locus coeruleus and decreased by
      imipramine in the dorsal raphe. Phenelzine increased locus coeruleus TH and
      imipramine increased dorsal raphe TPH2 gene expression in a glucocorticoid
      dependent manner, suggesting that increases in these enzymes were due to relief
      of inhibitory glucocorticoid signaling. We did not find antidepressant effects on
      GR or TH expression in the VTA or on mineralocorticoid receptor (MR) expression
      in any of the nuclei examined. Our findings represent a potential mechanism
      through which antidepressants and glucocorticoids could alter both HPA activity
      and mood via effects on brainstem GR, norepinephrine, and serotonin.

PMID- 19577554
TI  - Modification of phosphatidylserine by hypochlorous acid.
AB  - The binding of the heme enzyme myeloperoxidase to phosphatidylserine epitopes on
      the surface of non-vital polymorphonuclear leukocytes and other cells at
      inflammatory sites favours modifications of this phospholipid by myeloperoxidase
      products. As detected by MALDI-TOF mass spectrometry hypochlorous acid and the
      myeloperoxidase-hydrogen peroxide-chloride system convert 1,2-dipalmitoyl-sn
      glycero-3-phosphoserine into 1,2-dipalmitoyl-sn-glycero-3-phosphoacetaldehyde and
      1,2-dipalmitoyl-sn-glycero-3-phosphonitrile. A transient chlorimine derivative
      was detected using 4-chloro-alpha-cyanocinnamic acid as matrix in mass
      spectrometry only at short incubation times and supplying HOCl in two-fold
      excess. The decay of transient chlorinated products was followed by changes in
      absorbance spectra using O-phospho-l-serine to model the behavior of the serine
      head group in phosphatidylserine. N-Chlorimine and N-monochloramine derivatives
      decayed with half-life times of 1.5 and 57 min, respectively, at 22 degrees C and
      pH 7.4. N-Dichloramines decayed within few seconds under these conditions.

PMID- 19577555
TI  - Involvement of nitric oxide in 3-nitropropionic acid-induced depression of spinal
      reflexes in neonatal rat spinal cord in vitro.
AB  - The objective of the present investigation is to study the involvement of nitric
      oxide (NO) in 3-nitropropionic acid (3-NPA)-induced depression of spinal
      reflexes. Experiments were conducted on preparations of hemisected spinal cord
      isolated from 4 to 8 day old rats. Stimulation of a dorsal root evoked reflex
      potentials (monosynaptic, MSR; polysynaptic, PSR) in the corresponding segmental
      ventral root. Superfusion of 3-NPA (3.4 mM) depressed the spinal reflexes in a
      time-dependent manner and the reflexes were abolished after 35 min. The time
      required to produce 50% depression of the reflexes (T-50) was 17.8+/-5.3 min for
      MSR and 17.5+/-2.1 min for PSR. L-NAME (Nomega-nitro-L-arginine methyl ester; 100
      microM), a nitric oxide synthase inhibitor, antagonized the 3-NPA (3.4 mM)
      induced depression of reflexes and increased the T-50 values (34 and 30 min for
      MSR and PSR, respectively) significantly (P<0.05). In addition, hemoglobin (Hb,
      100 microM), a NO scavenger, blocked the 3-NPA-induced depression of reflexes
      significantly (P<0.05). T-50 values in Hb pretreated cords were 57 and 45 min for
      MSR and PSR, respectively which were greater than the cords pretreated with L
      NAME. The nitrite (NO(2)(-)) content of the 3-NPA exposed cords was 84 microM/g
      of tissue which was significantly greater than the control (13 microM/g; P<0.05).
      Pretreatment of cords with L-NAME or Hb antagonized the 3-NPA-induced increase in
      NO(2)(-). The results indicate that NO produced by 3-NPA is involved in the 3-NPA
      induced depression of spinal reflexes.

PMID- 19577556
TI  - Inverse relationship between Sec14l3 mRNA/protein expression and allergic airway
      inflammation.
AB  - Bronchial asthma is an inflammatory disease of the airways. The Sec14l3 gene,
      encoding a 45-kDa secretory protein, is specifically expressed in airway
      epithelium. Here, we report on the kinetics of Sec14l3 expression following
      allergic inflammation of the lung. Brown Norway rats were sensitized by
      intraperitoneal injection of ovalbumin, followed by challenge with aerosolized
      ovalbumin after a 3-week interval. This animal model showed many features similar
      to human allergic asthma: an increase in inflammatory cells such as eosinophils,
      lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid and
      histopathological alteration of lung tissue, exhibiting infiltration of these
      inflammatory cells and degeneration and necrosis of alveolar epithelium. These
      parameters reached their maximal level 24h after allergen challenge. In contrast,
      quantitative polymerase chain reaction analyses demonstrated a rapid and
      significant reduction of Sec14l3 mRNA in lung tissue and maximum reduction (to
      1.4% of the control) was observed at 24h. Pretreatment with dexamethasone
      significantly suppressed both the Sec14I3 mRNA reduction and all of the
      inflammatory changes. The 45-kDa secretory protein was identified in the
      supernatant of BAL fluids. Two-dimensional gel images of the supernatant proteome
      also revealed down-regulation of the protein following inflammation (to
      approximately 30% of the control at 24h). Thus, Sec14l3 expression is highly and
      inversely associated with the progression of airway inflammation. Sec14l3 mRNA
      and protein may function in the homeostasis of airway epithelial cells under
      normal conditions.

PMID- 19577557
TI  - Suppression of PC-1/ENPP-1 expression improves insulin sensitivity in vitro and
      in vivo.
AB  - Plasma cell membrane glycoprotein-1, or ectonucleotide
      pyrophosphatase/phosphodieterase (PC-1/ENPP1) has been shown to inhibit insulin
      signaling in cultured cells in vitro and in transgenic mice in vivo when
      overexpressed. Furthermore, both genetic polymorphism and increased expression of
      PC-1 have been reported to be associated with type 2 diabetes in humans. Thus it
      was proposed that PC-1 inhibition represents a potential strategy for the
      treatment of type 2 diabetes. However, it has not been proven that suppression of
      PC-1 expression or inhibition of its function will actually improve insulin
      sensitivity. We show in the current study that transient overexpression of PC-1
      inhibits insulin-stimulated insulin receptor tyrosine phosphorylation in HEK293
      cells, while knockdown of PC-1 with siRNA significantly increases insulin
      stimulated Akt phosphorylation in HuH7 human hepatoma cells. Adenoviral vector
      expressing a short hairpin RNA against mouse PC-1 (PC-1shRNA) was utilized to
      efficiently knockdown PC-1 expression in the livers of db/db mice. In comparison
      with db/db mice treated with a control virus, db/db mice treated with the PC
      1shRNA adenovirus had approximately 80% lower hepatic PC-1 mRNA levels,
      approximately 30% lower ambient fed plasma glucose, approximately 25% lower
      fasting plasma glucose, and significantly improved oral glucose tolerance. Taken
      together, these results demonstrate that suppression of PC-1 expression improves
      insulin sensitivity in vitro and in an animal model of diabetes, supporting the
      proposition that PC-1 inhibition is a potential therapeutic approach for the
      treatment of type 2 diabetes.

PMID- 19577559
TI  - Pharmacological properties of ATP-sensitive purinergic receptors expressed in
      human G292 osteoblastic cells.
AB  - We characterized the pharmacological properties of P2 receptors expressed in G292
      osteoblastic cells by studying the responses or changes in intracellular Ca(2+)
      level to P2 receptor agonists, antagonists and modulators. ATP induced robust
      responses in a concentration-dependent manner with EC(50) of 0.5+/-0.07 microM.
      While alpha,beta-methylene-ATP (alphabetameATP) and 2',3'-O-(4-benzoylbenzoyl)
      ATP (BzATP) were ineffective, ADP mimicked the action of ATP with EC(50) of 0.7+/
      0.2 microM. UTP and UDP also evoked responses with EC(50) of 2.0+/-0.4 microM and
      0.5+/-0.1 microM respectively, but their responses were much smaller, resulting
      in an order of the response magnitude: ATP~ADP>>UTP~UDP. The responses evoked by
      ATP and ADP were blocked by pyridoxal-5'-phosphate-6-azophenyl-2,4,-disulfonate
      (PPADS) with IC(50) of 3.0+/-0.05 microM and 5.0+/-0.4 microM respectively, but
      not by suramin up to 30 microM. ATP-evoked responses were insensitive to
      inhibition by trinitrophenyl-ATP (TNP-ATP) and brilliant blue G. ADP-evoked
      responses were significantly inhibited by 2'-deoxy-N(6)-methyladenosine-3',5'
      biphosphate (MRS2179) and 2-chloro-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine
      3',5'-bisphosphate (MRS2279) with IC(50) of 48+/-1.9 microM and 7.7+/-0.9 microM
      respectively. Taken together, these results provide strong evidence for
      functional expression of ATP-sensitive P2Y receptors and particularly P2Y(1)-like
      receptor in G292 cells.

PMID- 19577558
TI  - 17beta-Nitro-5alpha-androstan-3alpha-ol and its 3beta-methyl derivative:
      neurosteroid analogs with potent anticonvulsant and anxiolytic activities.
AB  - Many 17-substituted androstan-3alpha-ol analogs act as positive allosteric
      modulators of GABA(A) receptors and exert anticonvulsant and anxiolytic-like
      activity actions in animal models. The endogenous neurosteroid allopregnanolone
      (17beta-acetyl; 1) is among the most potent of these. Here we demonstrate that
      3alpha-hydroxy-17beta-nitro-5alpha-androstane (2b) and its 3beta-methyl analog
      (3alpha-hydroxy-3beta-methyl-17beta-nitro-5alpha-androstane; 2c) modulate GABA(A)
      receptors as assessed by [(35)S]t-butylbicyclo-phosphorothionate and
      [(3)H]flunitrazepam binding with potencies equivalent to or greater than 1. These
      compounds also had potencies equivalent to or greater than 1 in the
      pentylenetetrazol and 6Hz seizure models in the mouse. Furthermore, 2b exhibited
      anxiolytic-like activity in the elevated zero maze. The 3beta-hydroxy, 3alpha
      desmethyl analog (2a) was devoid of activity on GABA(A) receptors in vitro but
      had moderate activity in the seizure models, possibly as a result of
      epimerization in vivo at the 3-position. This conclusion was supported by the
      lack of in vivo activity of the 3beta-hydroxy, 3alpha-methyl analog (2d), which
      is not expected to undergo epimerization. We conclude that nitro can serve as a
      bioisostere for acetyl at the 17beta-position of 5alpha-androstan-3alpha-ol, such
      that the nitro analog fully retains the bioactivity of the endogenous
      neurosteroid at GABA(A) receptors.

PMID- 19577560
TI  - Protective effect of naringin against ischemic reperfusion cerebral injury:
      possible neurobehavioral, biochemical and cellular alterations in rat brain.
AB  - The present study was conducted with an aim to explore the possible role of
      naringin against ischemia reperfusion induced-neurobehavioral alterations,
      oxidative damage, cellular and histopathological alterations in cortex, striatum,
      hippocampus areas of brain. Male Wistar rats (200-220 g) were subjected to
      bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to
      induce reperfusion (I/R) cerebral injury. Naringin (50, 100 mg/kg, i.p.) was
      administered for 7 days continuously before animals were subjected to ischemia
      reperfusion injury. Various behavioral tests [locomotor activity, neurological
      score (inclined beam test), transfer latency, resistance to lateral push] and
      biochemical parameters (lipid peroxidation, nitrite level, reduced glutathione,
      superoxide dismutase and catalase activity), mitochondrial enzyme dysfunctions
      (Complex I, II, III and IV) in cortex, striatum, hippocampus of brain and
      histopathological alterations were assessed subsequently. Seven days naringin (50
      and 100 mg/kg) treatment significantly improved neurobehavioral alterations
      (improved locomotor activity, inclined beam walking and reduced resistance to
      lateral push, transfer latency) as compared to control ischemia reperfusion.
      Naringin (50 mg/kg and 100 mg/kg) treatment significantly attenuated oxidative
      damage as indicated by reduced lipid peroxidation, nitrite concentration,
      restored reduced glutathione and catalase activity and mitochondrial enzyme
      activities in cortex, striatum, cerebellum as compared to control (ischemia
      reperfusion) animals. In addition, naringin treatment significantly reversed
      histopathological alterations in cortex, striatum, hippocampus areas as compared
      to control (ischemia reperfusion). Present study suggests the protective effect
      of naringin and its therapeutic potential against ischemia reperfusion induced
      and related behavioral alterations in rats.

PMID- 19577562
TI  - Effect of laminin tyrosine-isoleucine-glycine-serine-arginine peptide on the
      growth of human prostate cancer (PC-3) cells in vitro.
AB  - The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide,
      corresponding to the 929-933 sequence of beta1 chain, is known to inhibit tumor
      growth and metastasis. In the present study, we observed that YIGSR not only
      inhibited the growth and migration of prostate cancer cells in a dose-dependent
      manner but also decreased mitochondrial membrane potential, inhibited ATP
      synthesis and increased caspase-9 activity. Investigation into the interaction of
      YIGSR with 67LR, the receptor for laminin and polyphenol (-) epigallocatechin-3
      gallate (EGCG) employing MVD (Molegro Virtual Docker, an integrated platform for
      predicting protein ligand interactions), revealed that the binding site of YIGSR
      was the same as that of EGCG that explains as to why YIGSR is able to inhibit the
      cytotoxicity of EGCG against PC-3 cells.

PMID- 19577563
TI  - Evaluation of the impacts of antibiotic drugs on PON 1; a major bioscavenger
      against cardiovascular diseases.
AB  - Paraoxonase 1 (PON1) is an antiatherogenic enzyme which is also an
      organophosphate hydrolyzer. It has crucial roles in detoxification of highly
      toxic substances and protecting LDL against oxidation. Decrease in the levels of
      this enzyme is a great risk for the patients with cardiovascular diseases,
      diabetes mellitus, chronic renal failure, rheumatoid arthritis, hyperthyroidism,
      and age-related macular degeneration. Therefore, inhibitors and activators of
      PON1 must be well-characterized, and drug studies would be a good starting point
      in this regard. Moreover, purification of PON1 has been a challenge for
      scientists due to its tight association with HDL. Here we report the purification
      of human serum PON1 using very simple methods and investigation of the
      interactions between the enzyme and some commonly used antibiotics. We purified
      PON1 from human serum with a high specific activity, and used the pure enzyme for
      inhibition studies. We observed that some antibiotics inhibit the enzyme at very
      low doses while some are efficient at higher doses. The antibiotics exhibited
      different inhibition mechanisms. We concluded that usage of these antibiotics
      would be very dangerous in some cases.

PMID- 19577561
TI  - Swertiamarin: a lead from Enicostemma littorale Blume. for anti-hyperlipidaemic
      effect.
AB  - We have investigated the hypolipidemic effects of swertiamarin an active lead
      isolated from a perennial herb Enicostemma littorale Blume. in high cholesterol
      fed rats. Swertiamarin (50 and 75 mg/kg) and atorvastatin (50 mg/kg) was given
      orally daily for seven consecutive day to the high cholesterol feed rats. Serum
      total cholesterol, triglycerides, low density lipoprotein and very low density
      lipoprotein were found to be markedly elevated in the high cholesterol fed
      control rats and these changes were significantly prevented in swertiamarin
      treated animals. However, there was no significant effect on serum high density
      lipoprotein level. The 3-hydroxy 3-methyl glutaryl Co A (HMG-Co A) reductase
      activity was significantly inhibited in swertiamarin and atorvastatin treated
      groups compared to high cholesterol fed control group. Swertiamarin was also
      found to increased excretion of fecal bile acid and total sterols compared to
      control animals. In conclusion our data suggest that swertiamarin possess high
      antiatherogenic potential and an effective cholesterol lowering agent and
      inhibition of HMG-Co A reductase may be one of the main mechanisms of
      hypolipidemic effect of swertiamarin.

PMID- 19577565
TI  - A novel SULF1 splice variant inhibits Wnt signalling but enhances angiogenesis by
      opposing SULF1 activity.
AB  - The importance of SULF1 in modulating the activities of multiple signalling
      molecules is now well established. Several studies, however, reported little or
      no effect of Sulf1 null mutations, questioning the relevance of this gene to in
      vivo development. The failure of SULF1 deletion to influence development may be
      predicted if one considers the involvement of a naturally occurring SULF1
      antagonist, generated by alternative splicing of the same gene. We demonstrate
      that while the previously described SULF1 (SULF1A) enhances Wnt signalling, the
      novel shorter isoform (SULF1B) inhibits Wnt signalling. Our studies show
      developmental stage specific changes in the proportions of SULF1A and SULF1B
      isoforms at both the mRNA and protein levels in many developing tissues, with
      particularly pronounced changes in developing and adult blood vessels. Unlike
      SULF1A, SULF1B promotes angiogenesis and is highly expressed in endothelial cells
      during early blood vessel development while SULF1A predominates in mature
      endothelial cells. We propose that the balance of two naturally occurring SULF1
      variants, with opposing functional activities, may regulate the overall net
      activities of multiple secreted factors and the associated signalling cascades
      essential for normal development and maintenance of most tissues.

PMID- 19577564
TI  - Deacetylase inhibition increases regulatory T cell function and decreases
      incidence and severity of collagen-induced arthritis.
AB  - Collagen-induced arthritis (CIA) is an established mouse model of disease with
      hallmarks of clinical rheumatoid arthritis. Histone/protein deacetylase
      inhibitors (HDACi) are known to inhibit the pathogenesis of CIA and other models
      of autoimmune disease, although the mechanisms responsible are unclear.
      Regulatory T cell (Treg) function is defective in rheumatoid arthritis. FOXP3
      proteins in Tregs are present in a dynamic protein complex containing histone
      acetyltransferase and HDAC enzymes, and FOXP3 itself is acetylated on lysine
      residues. We therefore investigated the effects of HDACi therapy on regulatory T
      cell function in the CIA model. Administration of an HDACi, valproic acid (VPA),
      significantly decreased disease incidence (p<0.005) and severity (p<0.03) in CIA.
      In addition, VPA treatment increased both the suppressive function of
      CD4(+)CD25(+) Tregs (p<0.04) and the numbers of CD25(+)FOXP3(+) Tregs in vivo.
      Hence, clinically approved HDACi such as VPA may limit autoimmune disease in vivo
      through effects on the production and function of FOXP3(+) Treg cells.

PMID- 19577566
TI  - Activity of plasma membrane beta-galactosidase and beta-glucosidase.
AB  - Human fibroblasts produce ceramide from sialyllactosylceramide on the plasma
      membranes. Sialidase Neu3 is known to be plasma membrane associated, while only
      indirect data suggest the plasma membrane association of beta-galactosidase and
      beta-glucosidase. To determine the presence of beta-galactosidase and beta
      glucosidase on plasma membrane, cells were submitted to cell surface
      biotinylation. Biotinylated proteins were purified by affinity column and
      analyzed for enzymatic activities on artificial substrates. Both enzyme
      activities were found associated with the cell surface and were up-regulated in
      Neu3 overexpressing cells. These enzymes were capable to act on both artificial
      and natural substrates without any addition of activator proteins or detergents
      and displayed a trans activity in living cells.

PMID- 19577567
TI  - The GroEL/GroES cis cavity as a passive anti-aggregation device.
AB  - The GroEL/GroES chaperonin folding chamber is an encapsulated space of
      approximately 65 A diameter with a hydrophilic wall, inside of which many
      cellular proteins reach the native state. The question of whether the cavity wall
      actively directs folding reactions or is playing a passive role has been open. We
      review past and recent observations and conclude that the chamber functions as a
      passive "Anfinsen cage" that prevents folding monomers from multimolecular
      aggregation.

PMID- 19577570
TI  - Targeted metabolomics identifies glucuronides of dietary phytoestrogens as a
      major class of MRP3 substrates in vivo.
AB  - BACKGROUND & AIMS: The physiologic function of the efflux transporter Multidrug
      Resistance Protein 3 (MRP3) remains poorly defined. In vitro, MRP3 transports
      several glucuronidated compounds, but the compounds transported under physiologic
      conditions are unknown. Knowledge of the compounds transported by MRP3 in vivo
      would greatly contribute to the elucidation of the physiologic function of this
      transport protein. METHODS: We used targeted metabolomics to identify substrates
      of MRP3 in vivo. Liquid chromatography coupled to mass spectrometry was used to
      specifically screen in plasma and urine of mice for compounds containing a
      glucuronic acid moiety. RESULTS: We found that several highly abundant compounds
      containing a glucuronic acid moiety have a much lower abundance in plasma and
      urine of Mrp3((-/-)) than of wild-type mice. We identified these as phytoestrogen
      glucuronides, and we show that MRP3 transports these compounds at high rates and
      with high affinity in vitro. CONCLUSIONS: We have identified the efflux
      transporter MRP3 as a major factor in the disposition of phytoestrogens, a class
      of compounds to which mammals are exposed via food of plant origin. Our targeted
      metabolomics approach is not restricted to MRP3 but applicable to many other
      transport proteins for which knockout mouse models are available. Similar screens
      could be developed for sulpho- and glutathione-conjugates, further increasing the
      potential of identifying new physiologic transporter substrates.

PMID- 19577568
TI  - Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a
      clinical outcome of human colon carcinoma.
AB  - BACKGROUND & AIMS: Regulatory T cells (Tregs) express the forkhead box
      transcription factor (FoxP3) and suppress the antitumor immune response. We
      investigated whether the intratumoral densities of FoxP3(+) and effector CD3(+)
      lymphocytes are associated with prognosis of patients with colon cancer. METHODS:
      FoxP3 and CD3 expression and location were determined in stage II and III colon
      carcinomas (n = 160) and normal mucosa (n = 25) by immunohistochemistry; CD4 and
      FoxP3 were localized by dual immunofluorescence microscopy. T-cell markers were
      compared with pathological variables, DNA mismatch repair status, and patient
      survival using Cox proportional hazards models. RESULTS: FoxP3(+) and CD3(+) T
      cell densities were increased in carcinomas compared with autologous normal
      mucosa (P < .0001). An increase in intraepithelial FoxP3(+) cells was associated
      with poor tumor differentiation (P = .038), female sex (P = .028), and advanced
      patient age (P = .042). FoxP3(+) cell density was not prognostic, yet patients
      with tumors with reduced intraepithelial CD3(+) T-cell densities had reduced
      disease-free survival (DFS) rates (hazard ratio [HR], 1.87 [95% confidence
      interval, 1.10-3.16]; P = .018). A low intraepithelial CD3(+)/FoxP3(+) cell ratio
      predicted reduced DFS (46.2% vs 66.7% survival at 5 years; HR, 2.17 [95%
      confidence interval, 1.11-4.23]; P = .0205). The prognostic impact of these
      markers was maintained when tumors were stratified by mismatch repair status. By
      multivariate analysis, a low CD3(+)/FoxP3(+) cell ratio (P= .0318) and low
      numbers of CD3(+) T cells (P = .0397) predicted shorter DFS times and were
      stronger prognostic variables than tumor stage or number of lymph node
      metastases. CONCLUSIONS: A low intraepithelial CD3(+)/FoxP3(+) cell ratio and
      reduced numbers of CD3(+) T cells were associated with shorter patient survival
      time, indicating the importance of an effector to Treg cell ratio in colon cancer
      prognosis.

PMID- 19577571
TI  - Evolution in a multi-host parasite: chronobiological circadian rhythm and
      population genetics of Schistosoma japonicum cercariae indicates contrasting
      definitive host reservoirs by habitat.
AB  - Schistosomiasis japonica is a disease of profound medical and veterinary
      importance which has remained endemic in many regions and has re-emerged where
      previously controlled in China. Although over 40 mammalian species are suspected
      as reservoirs for Schistosoma japonicum, their relative roles, particularly
      wildlife, remain to be ascertained. As cercarial emergence is a heritable trait
      shaped by the definitive hosts' behaviour, three chronobiological trials of
      cercarial emergence from field-collected snails from two contrasting ecological
      regions within China were performed, followed by genetic analyses of the
      parasites. Two distinct modes were identified, with late afternoon emergence
      mainly found in the hill region, compatible with a nocturnal rodent reservoir,
      and early emergence within the marshland consistent with a diurnal cattle
      reservoir. Furthermore, genetic analyses pointed to a clear separation between
      cercariae with different biological traits. The phenotypic and genotypic
      differentiation of the parasites identified here between and within two regions
      may indicate a strain complex. Such parasite diversity could, in turn, provide an
      explanation for the different infection scenarios observed between the two
      regions, and hence have important applied implications in terms of targeted
      control of key reservoirs.

PMID- 19577569
TI  - Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in
      nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Repair responses define the ultimate outcomes of liver
      disease. This study evaluated the hypothesis that fibrogenic repair in
      nonalcoholic fatty liver disease (NAFLD) is mediated by Hedgehog (Hh) pathway
      activation and consequent induction of epithelial-to-mesenchymal transitions
      (EMT) in ductular-type progenitors. METHODS: Immature ductular cells were exposed
      to Sonic hedgehog (Shh) in the presence or absence of the Hh inhibitor
      cyclopamine to determine whether Hh-pathway activation directly modulates EMT in
      liver progenitors. Potential biologic correlates of progenitor cell EMT were
      assessed using mice fed methionine-choline-deficient + ethionine (MCDE) diets
      with or without cyclopamine. The effects of increased Hh signaling on EMT and
      fibrogenic repair during diet-induced NAFLD were also compared in wild-type (WT)
      and Patched haplo-insufficient (Ptc(+/-)) mice. Finally, evidence of Hh-pathway
      activation and EMT was examined in liver sections from patients with NAFLD.
      RESULTS: In cultured progenitors, Shh repressed expression of epithelial genes
      and EMT inhibitors but induced genes that are expressed by myofibroblasts.
      Cyclopamine reversed these effects. In mouse NAFLD models, Hh-pathway activation,
      EMT, expansion of myofibroblastic populations, and liver fibrosis occurred.
      Cyclopamine inhibited Hh-pathway activation and induction of EMT. Ptc(+/-) mice,
      which have an overactive Hh pathway, exhibited sustained overinduction of Hh
      target genes and more EMT, myofibroblast accumulation, and fibrosis than WT mice.
      Numbers of Shh-producing cells and Hh-responsive ductular cells that expressed
      EMT markers increased in parallel with liver fibrosis in patients with NAFLD.
      CONCLUSIONS: Hh-mediated EMT in ductular cells contributes to the pathogenesis of
      cirrhosis in NAFLD.

PMID- 19577573
TI  - Structural insights into antibody recognition of mycobacterial polysaccharides.
AB  - Mycobacteria are major human pathogens responsible for such serious and
      widespread diseases as tuberculosis and leprosy. Among the evolutionary
      adaptations essential for pathogenicity in mycobacteria is a complex carbohydrate
      rich cell-wall structure that contains as a major immunomodulatory molecule the
      polysaccharide lipoarabinomannan (LAM). We report here crystal structures of
      three fragments from the non-reducing termini of LAM in complex with a murine
      antibody Fab fragment (CS-35Fab). These structures reveal for the first time the
      three-dimensional structures of key components of LAM and the molecular basis of
      LAM recognition at between 1.8- and 2.0-A resolution. The antigen-binding site of
      CS-35Fab forms three binding pockets that show a high degree of complementarity
      to the reducing end, the branch point and one of the non-reducing ends of the Y
      shaped hexasaccharide moiety found at most of the non-reducing termini of LAM.
      Structures of CS-35Fab bound to two additional tetrasaccharides confirm the
      general mode of binding seen in the hexasaccharide and indicate how different
      parts of LAM are recognized. Altogether, these structures provide a rational
      basis for understanding the overall architecture of LAM and identify the key
      elements of an epitope that may be exploited for the development of novel and
      more effective anti-mycobacterial vaccines. Moreover, this study represents the
      first high-resolution X-ray crystallographic investigation of oligofuranoside
      protein recognition.

PMID- 19577572
TI  - Cardiac extracellular matrix remodeling: fibrillar collagens and Secreted Protein
      Acidic and Rich in Cysteine (SPARC).
AB  - The cardiac interstitium is a unique and adaptable extracellular matrix (ECM)
      that provides a milieu in which myocytes, fibroblasts, and endothelial cells
      communicate and function. The composition of the ECM in the heart includes
      structural proteins such as fibrillar collagens and matricellular proteins that
      modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine
      (SPARC), a collagen-binding matricellular protein, serves a key role in collagen
      assembly into the ECM. Recent results demonstrated increased cardiac rupture,
      dysfunction and mortality in SPARC-null mice in response to myocardial infarction
      that was associated with a decreased capacity to generate organized, mature
      collagen fibers. In response to pressure overload induced-hypertrophy, the
      decrease in insoluble collagen incorporation in the left ventricle of SPARC-null
      hearts was coincident with diminished ventricular stiffness in comparison to WT
      mice with pressure overload. This review will focus on the role of SPARC in the
      regulation of interstitial collagen during cardiac remodeling following
      myocardial infarction and pressure overload with a discussion of potential
      cellular mechanisms that control SPARC-dependent collagen assembly in the heart.

PMID- 19577574
TI  - Modulation of calmodulin plasticity by the effect of macromolecular crowding.
AB  - In vitro biochemical reactions are most often studied in dilute solution, a poor
      mimic of the intracellular space of eukaryotic cells, which are crowded with
      mobile and immobile macromolecules. Such crowded conditions exert volume
      exclusion and other entropic forces that have the potential to impact chemical
      equilibria and reaction rates. In this article, we used the well-characterized
      and ubiquitous molecule calmodulin (CaM) and a combination of theoretical and
      experimental approaches to address how crowding impacts CaM's conformational
      plasticity. CaM is a dumbbell-shaped molecule that contains four EF hands (two in
      the N-lobe and two in the C-lobe) that each could bind Ca(2+), leading to
      stabilization of certain substates that favor interactions with other target
      proteins. Using coarse-grained molecular simulations, we explored the
      distribution of CaM conformations in the presence of crowding agents. These
      predictions, in which crowding effects enhance the population of compact
      structures, were then confirmed in experimental measurements using fluorescence
      resonance energy transfer techniques of donor- and acceptor-labeled CaM under
      normal and crowded conditions. Using protein reconstruction methods, we further
      explored the folding-energy landscape and examined the structural characteristics
      of CaM at free-energy basins. We discovered that crowding stabilizes several
      different compact conformations, which reflects the inherent plasticity in CaM's
      structure. From these results, we suggest that the EF hands in the C-lobe are
      flexible and can be thought of as a switch, while those in the N-lobe are stiff,
      analogous to a rheostat. New combinatorial signaling properties may arise from
      the product of the differential plasticity of the two distinct lobes of CaM in
      the presence of crowding. We discuss the implications of these results for
      modulating CaM's ability to bind Ca(2+) and target proteins.

PMID- 19577575
TI  - Uropathogenic E. coli adhesin-induced host cell receptor conformational changes:
      implications in transmembrane signaling transduction.
AB  - Urinary tract infection is the second most common infectious disease and is
      caused predominantly by type 1-fimbriated uropathogenic Escherichia coli (UPEC).
      UPEC initiates infection by attaching to uroplakin (UP) Ia, its urothelial
      surface receptor, via the FimH adhesins capping the distal end of its fimbriae.
      UP Ia, together with UP Ib, UP II, and UP IIIa, forms a 16-nm receptor complex
      that is assembled into hexagonally packed, two-dimensional crystals (urothelial
      plaques) covering >90% of the urothelial apical surface. Recent studies indicate
      that FimH is the invasin of UPEC as its attachment to the urothelial surface can
      induce cellular signaling events including calcium elevation and the
      phosphorylation of the UP IIIa cytoplasmic tail, leading to cytoskeletal
      rearrangements and bacterial invasion. However, it remains unknown how the
      binding of FimH to the UP receptor triggers a signal that can be transmitted
      through the highly impermeable urothelial apical membrane. We show here by cryo
      electron microscopy that FimH binding to the extracellular domain of UP Ia
      induces global conformational changes in the entire UP receptor complex,
      including a coordinated movement of the tightly bundled transmembrane helices.
      This movement of the transmembrane helix bundles can cause a corresponding
      lateral translocation of the UP cytoplasmic tails, which can be sufficient to
      trigger downstream signaling events. Our results suggest a novel pathogen-induced
      transmembrane signal transduction mechanism that plays a key role in the initial
      stages of UPEC invasion and receptor-mediated bacterial invasion in general.

PMID- 19577577
TI  - A chimeric fusion protein engineered with disparate functionalities-enzymatic
      activity and self-assembly.
AB  - The fusion of protein domains is an important mechanism in molecular evolution
      and a valuable strategy for protein engineering. We are interested in creating
      fusion proteins containing both globular and structural domains so that the final
      chimeric protein can be utilized to create novel bioactive biomaterials.
      Interactions between fused domains can be desirable in some fusion protein
      applications, but in this case the optimal configuration will enable the
      bioactivity to be unaffected by the structural cross-linking. To explore this
      concept, we have created a fusion consisting of a thermostable aldo-keto
      reductase, two alpha-helical leucine zipper domains, and a randomly coiled
      domain. The resulting protein is bifunctional in that (1) it can self-assemble
      into a hydrogel material as the terminal leucine zipper domains form interprotein
      coiled-coil cross-links, and (2) it expresses alcohol dehydrogenase and aldo-keto
      reductase activity native to AdhD from Pyrococcus furiosus. The kinetic
      parameters of the enzyme are minimally affected by the addition of the helical
      appendages, and rheological studies demonstrate that a supramolecular assembly of
      the bifunctional protein building blocks forms a hydrogel. An active hydrogel is
      produced at temperatures up to 60 degrees C, and we demonstrate the functionality
      of the biomaterial by monitoring the oxidation and reduction of the native
      substrates by the gel. The design of chimeric fusion proteins with both globular
      and structural domains is an important advancement for the creation of bioactive
      biomaterials for biotechnology applications such as tissue engineering,
      bioelectrocatalysis, and biosensing and for the study of native assembled enzyme
      structures and clustered enzyme systems such as metabolons.

PMID- 19577576
TI  - Chromophore packing leads to hysteresis in GFP.
AB  - Green fluorescent protein (GFP) possesses a unique folding landscape with a dual
      basin leading to the hysteretic folding behavior observed in experiment. While
      theoretical data do not have the resolution necessary to observe details of the
      chromophore during refolding, experimental results point to the chromophore as
      the cause of the observed hysteresis. With the use of NMR spectroscopy, which
      probes at the level of the individual residue, the hysteretic intermediate state
      is further characterized in the context of the loosely folded isomerized native
      like state {N(iso)} predicted in simulation. In the present study, several
      residues located in the lid of GFP indicate heterogeneity of the native states.
      Some of these residues show chemical shifts when the native-like intermediate
      {N(iso)} responsible for GFP's hysteretic folding behavior is trapped. Observed
      changes in the chromophore are consistent with increased flexibility or
      isomerization in {N(iso)} as predicted in recent theoretical work. Here, we
      observed that multiple chromophore environments within the native state are
      averaged in the trapped intermediate, linking chromophore flexibility to
      mispacking in the trapped intermediate. The present work is experimental evidence
      for the proposed final "locking" mechanism in GFP folding forming an incorrectly
      or loosely packed barrel under intermediate (hysteretic) folding conditions.

PMID- 19577578
TI  - Pathways and mechanisms for product release in the engineered haloalkane
      dehalogenases explored using classical and random acceleration molecular dynamics
      simulations.
AB  - Eight mutants of the DhaA haloalkane dehalogenase carrying mutations at the
      residues lining two tunnels, previously observed by protein X-ray
      crystallography, were constructed and biochemically characterized. The mutants
      showed distinct catalytic efficiencies with the halogenated substrate 1,2,3
      trichloropropane. Release pathways for the two dehalogenation products, 2,3
      dichloropropane-1-ol and the chloride ion, and exchange pathways for water
      molecules, were studied using classical and random acceleration molecular
      dynamics simulations. Five different pathways, denoted p1, p2a, p2b, p2c, and p3,
      were identified. The individual pathways showed differing selectivity for the
      products: the chloride ion releases solely through p1, whereas the alcohol
      releases through all five pathways. Water molecules play a crucial role for
      release of both products by breakage of their hydrogen-bonding interactions with
      the active-site residues and shielding the charged chloride ion during its
      passage through a hydrophobic tunnel. Exchange of the chloride ions, the alcohol
      product, and the waters between the buried active site and the bulk solvent can
      be realized by three different mechanisms: (i) passage through a permanent
      tunnel, (ii) passage through a transient tunnel, and (iii) migration through a
      protein matrix. We demonstrate that the accessibility of the pathways and the
      mechanisms of ligand exchange were modified by mutations. Insertion of bulky
      aromatic residues in the tunnel corresponding to pathway p1 leads to reduced
      accessibility to the ligands and a change in mechanism of opening from permanent
      to transient. We propose that engineering the accessibility of tunnels and the
      mechanisms of ligand exchange is a powerful strategy for modification of the
      functional properties of enzymes with buried active sites.

PMID- 19577579
TI  - Immune impairment in HIV infection: existence of risky and immunodeficiency
      thresholds.
AB  - Results of several studies show that some DC populations are susceptible to HIV.
      Modulation of DCs by HIV infection, in particular interference of the antigen
      presenting function of DCs, is a key aspect in viral pathogenesis and contributes
      to viral evasion from immunity because the loss of the DC function engenders some
      impairment effects for a proliferation of CTL responses, which play an important
      role in the immune response to HIV. As described herein, we use a simple
      mathematical model to examine virus-immune dynamics over the course of HIV
      infection in the context of the immune impairment effects. A decrease of the DC
      number and function during the course of HIV-1 infection is observed. Therefore,
      we simply assumed that the immune impairment rate increases over the HIV
      infection. Under the assumption, four processes of the disease progression
      dynamics of our model are classifiable according to their virological properties.
      It is particularly interesting a typical disease progression presents a "risky
      threshold" and an "immunodeficiency threshold". Regarding the former, the immune
      system might collapse when the impairment rate of HIV exceeds a threshold value
      (which corresponds to a transcritical bifurcation point). For the latter, the
      immune system always collapses when the impairment rate exceeds the value (which
      corresponds to a saddle-node bifurcation point). To test our theoretical
      framework, we investigate the existence and distribution of these thresholds in
      10 patients.

PMID- 19577580
TI  - Mutate now, die later. Evolutionary dynamics with delayed selection.
AB  - We analyze here the evolutionary consequences of selection with delay in a
      population genetics context. In the classical works on evolutionary dynamics, an
      individual produces off-springs in direct proportion to its fitness, a process in
      which mutations may occur. In the present scenario of delayed selection,
      individuals that acquire deleterious mutations can still reproduce unharmed for
      several generations. During this time delay, the damage passed on to off-springs
      can potentially be repaired by subsequent compensatory mutations. In the absence
      of such a repair, the individual becomes sterile. Here we study the population
      genetic effects of such a time delay by means of both numerical simulations and
      theoretical modeling. The results show that delayed selection lowers the
      extinction threshold, endangering the survival of the population. Surprisingly,
      however, no traces of this delay effect are encountered in the sequence diversity
      of the population. These conclusions suggest that delayed selection is hard to
      detect in genetic data and thus could be a wide-spread but rarely detected
      phenomenon.

PMID- 19577581
TI  - Tripartite synapses: roles for astrocytic purines in the control of synaptic
      physiology and behavior.
AB  - Astrocytes are known to release several transmitters to impact neuronal activity.
      Cell-specific molecular genetic attenuation of vesicular release has shown that
      ATP is a primary astrocytic transmitter in situ and in vivo. In this review, we
      discuss the biology of astrocytic ATP release highlighting the exciting discovery
      that lysosomes might be primary stores for the release of this gliotransmitter.
      In addition, we discuss the role of ATP and its metabolite adenosine on synaptic
      transmission and the coordination of synaptic networks. Finally, we discuss the
      recent elucidation of the involvement of this form of glial signaling in the
      modulation of mammalian behavior. By controlling neuronal A1-receptor signaling,
      astrocytes modulate mammalian sleep homeostasis and are essential for mediating
      the cognitive consequences of sleep deprivation. These discoveries begin to paint
      a new picture of brain function in which slow-signaling glia modulate fast
      synaptic transmission and neuronal firing to impact behavioral output. Because
      these cells have privileged access to synapses, they may be valuable targets for
      the development of novel therapies for many neurological and psychiatric
      conditions.

PMID- 19577583
TI  - How barn owls (Tyto alba) visually follow moving voles (Microtus socialis) before
      attacking them.
AB  - The present study focused on the movements that owls perform before they swoop
      down on their prey. The working hypothesis was that owl head movements reflect
      the capacity to efficiently follow visually and auditory a moving prey. To test
      this hypothesis, five tame barn owls (Tyto alba) were each exposed 10 times to a
      live vole in a laboratory setting that enabled us to simultaneously record the
      behavior of both owl and vole. Bi-dimensional analysis of the horizontal and
      vertical projections of movements revealed that owl head movements increased in
      amplitude parallel to the vole's direction of movement (sideways or away
      from/toward the owl). However, the owls also performed relatively large
      repetitive horizontal head movements when the voles were progressing in any
      direction, suggesting that these movements were critical for the owl to
      accurately locate the prey, independent of prey behavior. From the pattern of
      head movements we conclude that owls orient toward the prospective clash point,
      and then return to the target itself (the vole) - a pattern that fits an
      interception rather than a tracking mode of following a moving target. The large
      horizontal component of head movement in following live prey may indicate that
      barn owls either have a horizontally narrow fovea or that these movements serve
      in forming a motion parallax along with preserving image acuity on a horizontally
      wide fovea.

PMID- 19577582
TI  - Increased O-GlcNAc causes disrupted lens fiber cell differentiation and
      cataracts.
AB  - Diminished proteolytic functionality in the lens may cause cataracts. We have
      reported that O-GlcNAc is an endogenous inhibitor of the proteasome. We
      hypothesize that in the lens there is a cause-and-effect relationship between
      proteasome inhibition by O-GlcNAc, and cataract formation. To demonstrate this,
      we established novel transgenic mouse models to over-express a dominant-negative
      form of O-GlcNAcase, GK-NCOAT, in the lens. Expression of GK-NCOAT suppresses
      removal of O-GlcNAc from proteins, resulting in increased levels of O-GlcNAc in
      the lenses of our transgenic mice, along with decreased proteasome function. We
      observed that transgenic mice developed markedly larger cataracts than controls
      and lens fiber cell denucleation was inhibited. Our study suggests that increased
      O-GlcNAc in the lens could lead to cataract formation and attenuation of lens
      fiber cell denucleation by inhibition of proteasome function. These findings may
      explain why cataract formation is a common complication of diabetes since O
      GlcNAc is derived from glucose.

PMID- 19577584
TI  - Physiological and pathophysiological applications of sensitive ELISA methods for
      urinary deoxycorticosterone and corticosterone in rodents.
AB  - Deoxycorticosterone (DOC: a weak mineralocorticoid) is the precursor to
      corticosterone (B: the major glucocorticoid in rodents) and aldosterone (the
      major mineralocorticoid). The genes Cyp11b1 and Cyp11b2 that encode the enzymes
      responsible for DOC to B (11beta-hydroxylase) and DOC to aldosterone (aldosterone
      synthase) conversions are located on the same chromosome. The aim of this study
      was to develop sensitive and specific ELISA methods to quantify urinary DOC and B
      concentrations to assess the physiological and genetic control of the Cyp11b1/b2
      locus. Antibodies raised in rabbits against DOC and B and horse radish peroxidase
      goat anti-rabbit IgG enzyme tracer were used to develop the assays. Urine samples
      collected from mice held in metabolic cages were extracted with dichloromethane
      and reconstituted in assay buffer. The assays were validated for specificity,
      sensitivity, parallelism, accuracy and imprecision. Cross-reactivities with major
      interfering steroids were minimal: DOC assay (progesterone=0.735% and
      corticosterone=0.045%), and for B assay (aldosterone=0.14%, 11-dehydro-B=0.006%,
      cortisol=0.016% and DOC=0.04%) and minimum detection limit for DOC ELISA was 2.2
      pg/mL (6.6 pmol/L), and for B ELISA was 6.2 pg/mL (17.9 pmol/L). The validity of
      urinary DOC and B ELISAs was confirmed by the excellent correlation between the
      results obtained before and after solvent extraction and HPLC (DOC ELISA:
      Y=1.092X-0.054, R(2)=0.988; B ELISA: Y=1.047X-0.226, R(2)=0.996). Accuracy
      studies, parallelism and imprecision data were determined and all found to be
      satisfactory. The methods were used in a series of metabolic cage studies which
      demonstrated that (i) females produce more DOC and corticosterone than males;
      (ii) DOC and corticosterone respond to ACTH treatment but not dietary sodium
      restriction; (iii) DOC:B ratios in Cyp11b1 null mice were >200-fold greater than
      wild type.

PMID- 19577586
TI  - Altered integrity and decreased expression of hepatocyte tight junctions in
      rifampicin-induced cholestasis in mice.
AB  - Rifampicin is a well-known hepatotoxicant, but little is known about the
      mechanism of rifampicin-induced hepatotoxicity. The aim of this study was to
      characterize the expression and localization of hepatocyte tight junctions in
      rifampicin-induced cholestasis in mice. Cholestasis was induced by administration
      of rifampicin (200 mg/kg) for 7 consecutive days or treatment with a single dose
      of rifampicin (200 mg/kg) by gastric intubation. The expression of mRNA for
      hepatic zonula occludens (ZO)-1, ZO-2, ZO-3, occludin and claudin-1 was
      determined using RT-PCR. Localization of ZO-1 and occludin was detected using
      immunofluorescence. Results showed that there was an 82-fold increase in the
      conjugated bilirubin in serum in rifampicin-treated mice. In addition, an 8-fold
      increase in total bile acid in serum was observed after a seven-day
      administration of rifampicin. The integrity of hepatocyte ZO-1 and occludin was
      altered by a seven-day administration of rifampicin. Importantly, the integrity
      and intensity of hepatocyte tight junctions were altered as early as 30 min after
      a single dose of rifampicin. The expression of hepatic ZO-1 and ZO-2 mRNA was
      significantly decreased, beginning as early as 30 min and remaining a lower level
      12 h after a single dose of rifampicin. Taken together, these results suggest
      that the altered integrity and internalization of hepatocyte tight junctions are
      associated with rifampicin-induced cholestasis.

PMID- 19577585
TI  - The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA
      analogues on short term and long term memory in the mouse.
AB  - Neurosteroids have been reported to modulate memory processes in rodents. Three
      analogues of dehydroepiandrosterone (DHEA), two of them previously described
      (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta
      hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were
      evaluated on memory. This study examined their effects on long term and short
      term memory in male (6 weeks old) NMRI mice in comparison with the reference
      drug. Long term memory was assessed using the passive avoidance task and short
      term memory (spatial working memory) using the spontaneous alternation task in a
      Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion
      were measured. In all tests, DHEA and analogues were injected at three equimolar
      doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered
      immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved
      retention in passive avoidance test. Without effect per se in the spatial working
      memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)
      induced deficit in spontaneous alternation. These data suggested an action of
      DHEA and analogues in consolidation of long term memory particularly when
      emotional components are implied. Moreover, data indicated that pharmacological
      modulation of DHEA as performed in this study provides derivatives giving the
      same mnemonic profile than reference molecule.

PMID- 19577587
TI  - Effect of heparin treatment on the expression and activity of different ion
      motive P-type ATPase isoforms from mouse extensor digitorum longus muscle during
      degeneration and regeneration after Bothrops jararacussu venom injection.
AB  - Ca(2+) ions are essential to myonecrosis, a serious complication of snake
      envenomation, and heparin seems to counteract this effect. We investigated the
      effect of local injection of Bothrops jararacussu venom in mouse fast-twitch
      extensor digitorum longus (EDL) muscle, without or with heparin, on
      functional/molecular alterations of two central proteins involved in
      intracellular Ca(2+) homeostasis, sarco(endo)plasmic reticulum Ca(2+)-ATPase
      (SERCA) and Na(+)/K(+)-ATPase. EDL-specific SERCA1 isoform expression dropped
      significantly just after venom administration (up to 60% compared to control EDL
      values at days 1 and 3; p<0.05) while SERCA2 and Na(+)/K(+)-ATPase alpha(1)
      isoform expression increased at the same time (3-6- and 2-3-fold, respectively;
      p<0.05). Although not significant, Na(+)/K(+)-ATPase alpha(2) isoform followed
      the same trend. Except for SERCA2, all proteins reached basal levels at the 7th
      day. Intravenous heparin treatment did not affect these profiles. Ca(2+)-ATPase
      activity was also decreased during the first days after venom injection, but here
      heparin was effective to reinstate activity to control levels within 3 days. We
      also showed that B. jararacussu venom directly inhibited Ca(2+)-ATPase activity
      in a concentration-dependent manner. Our results indicate that EDL SERCA and
      Na(+)/K(+)-ATPase are importantly affected by B. jararacussu venom and heparin
      has protective effect on activity but not on protein expression.

PMID- 19577588
TI  - Lonomia obliqua caterpillar envenomation causes platelet hypoaggregation and
      blood incoagulability in rats.
AB  - Envenomation caused by Lonomia obliqua is a public health hazard in Southern
      Brazil. Envenomed victims present severe hemorrhagic syndrome that can progress
      to intracranial hemorrhage and death. To understand the mechanisms that lead to
      hemorrhage, we investigated the platelet dysfunction and blood coagulation
      disturbances following experimental envenomation in rats. L. obliqua bristle
      extract was injected (s.c.) and blood collected at different times post-venom
      administration for determination of platelet response and analysis of blood
      coagulation. Rats presented hypofibrinogenemia and platelet hypoaggregation in
      platelet rich plasma (PRP). After addition of exogenous fibrinogen to PRP,
      platelet hypoaggregation was not corrected. Interestingly, normoaggregation was
      observed when platelets were separated from plasma. In addition, incubation of
      plasma from envenomed rats inhibits aggregation response of normal washed
      platelets. These results indicate that an aggregation inhibitor is generated in
      plasma during envenomation. Moreover, rats presented an increase in nitric oxide
      plasmatic levels which coincided with maximum inhibition in platelet aggregation.
      Animals also showed blood incoagulability and a significant increase in thrombin,
      plasmin and urokinase plasmatic activities. Despite this intravascular thrombin
      generation, only a slight decrease in platelet numbers was detected. Certainly,
      the platelet hypoaggregation and blood incoagulability described herein
      contribute to systemic bleeding observed in patients.

PMID- 19577589
TI  - The role of monocularly visible regions in depth and surface perception.
AB  - The mainstream of binocular vision research has long been focused on
      understanding how binocular disparity is used for depth perception. In recent
      years, researchers have begun to explore how monocular regions in binocularly
      viewed scenes contribute to our perception of the three-dimensional world. Here
      we review the field as it currently stands, with a focus on understanding the
      extent to which the role of monocular regions in depth perception can be
      understood using extant theories of binocular vision.

PMID- 19577590
TI  - Adaptation to objects in the lateral occipital complex (LOC): shape or semantics?
AB  - A change in the basic-level class when viewing a sequence of two objects produces
      a large release from adaptation in LOC compared to when the images are identical.
      Is this due to a change in semantics or shape? In an fMRI-adaptation experiment,
      subjects viewed a sequence of two objects and judged whether the stimuli were
      identical in shape. Different-shaped stimuli could be from the same or different
      basic-level classes, where the physical similarities of the pairs in the two
      conditions were equated by a model of simple cell similarity. BOLD responses in
      LOC for the two conditions were equivalent, and higher than that of the identical
      condition, indicating that LOC is sensitive to shape rather than to basic-level
      semantics.

PMID- 19577591
TI  - Dr. Jekyll and Mr. Hyde: a short history of anthrax.
AB  - The anthrax letters crisis, following the discovery of a major bacterial warfare
      program in the USSR and the realization that Irak had been on the verge of using
      anthrax as a weapon during the first Gulf war, had the consequence of putting
      anthrax back on the agenda of scientists. Fortunately, although it was mostly
      unknown by the public before these events, it was far from unknown by
      microbiologists. Already mentioned in the bible as a disease of herbivores, it
      remained a major cause of death for animals all over the planet until the end of
      the 19th century, with occasional, sometimes extensive, contamination of human
      beings. The aetiological agent, Bacillus anthracis, was identified by French and
      German scientists in the 1860s and 1870s. This was the first time that a disease
      could be attributed to a specific microorganism. The discovery by Koch that this
      bacterium formed spores greatly contributed to the understanding of the disease
      epidemiology. Studies on the pathophysiology of anthrax led to the identification
      of two major virulence factors, the capsule, protecting the bacilli against
      phagocytosis, and a tripartite toxin. The latter consists of two toxins with a
      common component (protecting antigen, PA) that allows the binding to and
      penetration into cells of two enzymes, the oedema factor EF, a calmodulin
      dependent adenylate cyclase, and the lethal factor LF, a specific zinc
      metalloprotease. The primary targets of these toxins would seem to be cells of
      innate immunity that would otherwise impair multiplication of the bacilli. If
      detected early enough, B. anthracis infections can be stopped by using
      antibiotics such as ciprofloxacin. Infection of animals can be prevented by the
      administration of vaccines, the first of which was developed by Pasteur after an
      historical testing at Pouilly-le-Fort which marked the beginning of the science
      of vaccines.

PMID- 19577592
TI  - Maternal transfer and transcriptional onset of immune genes during ontogenesis in
      Atlantic cod.
AB  - The immune system in teleosts is not completely developed during embryonic and
      larval stages and immune competence is assumed to be restricted. This study is
      the first to address whether immune transcripts are maternally transferred to
      offspring and when immune genes are transcriptionally active in Atlantic cod
      (Gadus morhua). In unfertilised eggs, transcripts encoding lysozyme and
      cathelicidin were found indicating maternal transfer of antibacterial
      transcripts. Lysozyme activity was also present at this stage suggesting the
      presence of a functional protein. Transcripts of two other putative antibacterial
      genes (hepcidin and pentraxin) and antiviral genes (ISG15 and LGP2) were absent
      in unfertilised eggs. The transcriptional onset of these genes occurred during
      the gastrula period. Transcripts of the heavy chain constant regions of the
      immunoglobulin (Ig) D, membrane-associated and secreted form of IgM were absent
      in unfertilised eggs. Transcription of the heavy chain locus commenced at low
      levels during the segmentation period indicating the onset of B-cell development.
      Most innate immune genes showed an increase in transcription around hatch and
      first feeding, indicating a preparation for increased pathogen exposure at this
      time. Prior to and during metamorphosis all genes showed a pronounced elevation
      in transcript levels indicating a further maturation of the immune system during
      this period.

PMID- 19577593
TI  - Comparison of effects of green tea catechins on apicomplexan hexose transporters
      and mammalian orthologues.
AB  - Here we have investigated the inhibitory properties of green tea catechins on the
      Plasmodium falciparum hexose transporter (PfHT), the Babesia bovis hexose
      transporter 1 (BboHT1) and the mammalian facilitative glucose transporters, GLUT1
      and GLUT5, expressed in Xenopus laevis oocytes. (-)-Epicatechin-gallate (ECG) and
      (-)-epigallocatechin-gallate (EGCG) inhibited D-glucose transport by GLUT1 and
      PfHT, and D-fructose transport by GLUT5, with apparent K(i) values between 45 and
      117 microM. BboHT1 was more potently inhibited by the ungallated catechins (-)
      epicatechin (EC) and (-)-epigallocatechin (EGC), with apparent K(i) values of 108
      and 168 microM, respectively. Site-directed mutagenesis experiments provided
      little further support for previously reported models of catechin binding to
      hexose transporters. Furthermore, P. falciparum growth inhibition by catechins
      was not affected by the external D-glucose concentration. Our results provide new
      data on the inhibitory action of catechins against sugar transporters but were
      unable to elucidate the antimalarial mechanism of action of these agents.

PMID- 19577594
TI  - Analysis of Swedish Bordetella pertussis isolates with three typing methods:
      characterization of an epidemic lineage.
AB  - Three Bordetella pertussis typing methods, pulsed-field gel electrophoresis
      (PFGE), multi-locus sequence typing (MLST), and multi-locus variable number
      tandem repeat analysis (MLVA) were compared using a collection of Swedish
      strains. Of the three typing methods used, PFGE was found to be the most
      discriminatory. MLVA and MLST were less discriminatory, but may be valuable for
      strain discrimination when culture is not possible as they are based on PCR. The
      combination of MLVA/MLST was found to be equally discriminatory as PFGE and
      should therefore also be considered. The relationship between predominant
      lineages in Sweden and The Netherlands, characterized by the PFGE type BpSR11 and
      the allele for the pertussis toxin promoter ptxP3, respectively, was
      investigated. Linkage was found between the PFGE type BpSR11 and ptxP3 in that
      all BpSR11 strains carried ptxP3. On the other hand ptxP3 was found in several
      other PFGE-types. The presence of the ptxP3 allele in different genetic
      backgrounds may indicate horizontal gene transfer within B. pertussis or
      homoplasy. Alternatively, this observation may be due to convergence of PFGE
      types.

PMID- 19577595
TI  - Up-regulation of cocaine- and amphetamine-regulated transcript (CART) in the rat
      nucleus accumbens after repeated electroconvulsive shock.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide regulates appetite,
      reward, and mood. CART expression is regulated via the protein kinase A (PKA)
      pathway, and electroconvulsive shock (ECS), an efficient antipsychotic and
      antidepressant measure, activates PKA-related signaling. Thus, we hypothesized
      that ECS may regulate the expression of CART. ECS given daily for five
      consecutive days increased CART mRNA and protein in the rat nucleus accumbens
      (NAc), accompanied by an increase in CREB phosphorylation. Our results suggest
      that ECS-induced CART up-regulation might be associated with PKA-CREB signaling,
      but the causal direction remains to be elucidated in future studies.

PMID- 19577596
TI  - Isolation of cobalt hyper-resistant mutants of Saccharomyces cerevisiae by in
      vivo evolutionary engineering approach.
AB  - Cobalt is an important element with magnetic properties used in various
      industrial applications, but is also needed for biological activity. Very little
      is known about the cellular response of living systems to cobalt stress. Towards
      investigating this mechanism, we isolated individual Saccharomyces cerevisiae
      cells resistant to high cobalt concentrations up to 8 mmoll(-1), by employing
      four different 'in vivo' evolutionary engineering strategies: selection under
      constant or gradually increasing stress levels, and selection under continuous or
      pulse exposure to cobalt stress. Selection under continuous exposure to gradually
      increasing cobalt stress levels yielded the most resistant cell population to
      cobalt. However, the resistance was highly heterogeneous within the mutant
      populations ranging from 3- to 3700-fold survival rate of isolated individuals to
      8 mmoll(-1) CoCl2 in the most resistant population. Moreover, cobalt-resistant
      individual colonies were associated with 2-4-times lower intracellular cobalt
      contents as compared to wild-type, and with cross-resistance to metals such as
      nickel, zinc, manganese, but not to copper and chromium ions. Contrary to mutants
      evolved under continuous exposure to cobalt, those isolated by pulse exposure
      strategy also exhibited resistance to heat shock and hydrogen peroxide stress.
      Taken together, this study reinforced the fact that evolutionary engineering is
      useful in selecting strains with very specific phenotypes, and further
      illustrated the importance of the strategy chosen to isolate the best evolved
      strain.

PMID- 19577597
TI  - Dry-coated microprojection array patches for targeted delivery of
      immunotherapeutics to the skin.
AB  - Dry-coated microprojections (MPs) deliver vaccine to abundant immunogenic cells
      within the skin to induce immune responses. Success in this targeted vaccine
      delivery relies on overcoming the challenges of dry-coating the vaccine onto the
      very small (<or=90 microm length) and densely packed (approximately 20,000 cm(
      2)) MPs. In this paper, we show that a gas-jet drying coating method achieves the
      desired uniform coating. The coating approach is robustly demonstrated on
      compounds representative of a range of immunotherapeutics (e.g. DNA, proteins),
      with each uniformly coated on thousands of MPs. Furthermore, the dry-coating
      remains intact during skin insertion, and then releases within the wet skin
      cellular environment within 3 min. Finally, we applied ovalbumin protein coated
      MP patches to immunise mice, achieving comparable antibody levels (p=0.08) with
      needle and syringe intramuscular injection. In summary, this paper presents a
      simple, practical and versatile method to achieve uniform coating on very small
      and densely packed MPs for a needle-free and targeted vaccine delivery
      technology.

PMID- 19577598
TI  - Release, biological potency, and biochemical integrity of recombinant human
      platelet-derived growth factor-BB (rhPDGF-BB) combined with Augment(TM) Bone
      Graft or GEM 21S beta-tricalcium phosphate (beta-TCP).
AB  - Over 10 million surgical procedures are performed annually in the United States
      to treat musculoskeletal injuries, and a significant portion of these involve
      orthopedic bone grafting. The goals of the study were to evaluate the in vitro
      and in vivo release kinetics, biological potency and biochemical integrity of
      rhPDGF-BB combined with large (1000-2000 microm) and small (250-1000 microm) beta
      TCP particles. Recombinant human platelet-derived growth factor B homodimer
      (rhPDGF-BB) is a protein growth factor under development as a therapeutic for
      accelerating bone healing. Release of the protein was monitored in vitro by
      ELISA, and in vivo by measurement of radioactive rhPDGF-BB implanted in rat
      calvarial defects. Biological activity was measured using a cell-based bioassay,
      and biochemical integrity was determined by SDS-PAGE and high pressure size
      exclusion chromatography (HPSEC). Release of rhPDGF-BB occurred rapidly from beta
      TCP both in vitro and in vivo. Almost 100% of the rhPDGF-BB was recovered from
      large and small beta-TCP after 90 min in vitro. Approximately 90% of the rhPDGF
      BB was depleted from calvarial defect sites within 72 h of implantation. RhPDGF
      BB retained 100% of its biological potency compared to reference standard rhPDGF
      BB, manifested as a single band at ~30 kDa by SDS-PAGE and a single peak eluted
      after 13 min by HPSEC following release from beta-TCP. RhPDGF-BB is rapidly
      released from large and small beta-TCP particles and is biochemically unaltered
      following release.

PMID- 19577599
TI  - CPP-protein constructs induce a population of non-acidic vesicles during
      trafficking through endo-lysosomal pathway.
AB  - The major limitation in the application of bioactive molecules is their low
      permeation across plasma membrane. Effective transporters - cell-penetrating
      peptides (CPPs) - are utilized to enhance uptake of various cargo upon attachment
      to its sequences. Still, information about relevance of different endocytic
      routes during CPP-cargo internalization is ambiguous and underlying mechanism(s)
      of intracellular trafficking is even less understood. We first defined
      involvement of recycling pathway in trafficking of 3 different CPPs -
      transportan, oligoarginine and Tat - complexed to avidin-TexasRed in Cos-7 cells
      in relation to trans-Golgi network spatially constraining recycling endosomes. By
      confocal microscopy, only a negligible fraction of complexes-containing vesicles
      were found inside trans-Golgi ring suggesting its marginal role in CPP-mediated
      delivery. Secondly, we characterized engagement of endo-lysosomal pathway to
      assess acidity of complexes-containing vesicles. CPPs induced 3 different
      populations of complexes-containing vesicles which size and proportion depended
      on CPP, time and concentration. In time, more complexes were targeted to low-pH
      structures. However, a population of complexes-containing vesicles was observed
      to retain rather neutral pH. Induction of vesicles with non-acidic pH generated
      i.e. by caveolin-dependent endocytosis or by CPPs themselves during intracellular
      trafficking could be the key step in inducement of escape of complexes from
      endosomal structures, a limiting step in effective cargo delivery by CPPs.

PMID- 19577601
TI  - Dating and eating. Beliefs about dating foods among university students.
AB  - Dating is an important courtship activity in the U.S., and food consumption is
      part of dating events. Students use dating scripts to guide decisions and
      behaviors on dates, and perform scripts on dates to construct positive impression
      management. This study examined how students conceptualized dating foods. A
      questionnaire was administered in one large university class, and data from 301
      students were analyzed. Students were asked to name three dating foods, three
      foods that are not dating foods, what makes foods dating foods, and what makes
      foods not dating foods. Findings revealed that both common and uncommon foods
      were named as dating and not dating foods. Alcoholic beverages were sometimes
      named as dating foods. Women often named feminine foods (considered appropriate
      for females) as dating foods, but men were not more likely to name masculine
      foods (considered appropriate for males) as dating foods. Neat and easy-to-eat
      foods were often named as dating foods, while pungent foods and foods causing bad
      breath were named as not dating foods. These findings support the conception that
      dating scripts guide thinking about food choices to enhance impression
      management. Dating food choices are important for current health and as potential
      precursors for long-term eating relationships like marriage.

PMID- 19577600
TI  - L-Asparaginase encapsulated intact erythrocytes for treatment of acute
      lymphoblastic leukemia (ALL).
AB  - As a primary drug for the treatment of acute lymphoblastic leukemia (ALL),
      encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been
      popular to circumvent immunogenicity from the exogenous protein. Unlike existing
      methods that perturbs RBC membranes, we introduce a novel method of RBC
      incorporation of proteins using the membrane-translocating low molecular weight
      protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a
      model protein conjugate, has shown significant fluorescence inside RBCs. Surface
      morphology by scanning electron microscopy of the RBCs loaded with LMWP-ASNase
      was indistinguishable with normal RBCs. These drug loaded RBCs also closely
      resembled the profile of the native erythrocytes in terms of osmotic fragility,
      oxygen dissociation and hematological parameters. The in vivo half-life of enzyme
      activity after administering 8 units of RBC/LMWP-ASNase in DBA/2 mice was
      prolonged to 4.5+/-0.5 days whereas that of RBCs loaded with ASNase via a
      hypotonic method was 2.4+/-0.7 days. Furthermore, the mean survival time of DBA/2
      mice bearing mouse lymphoma cell L5178Y was improved by approximately 44%
      compared to the saline control group after treatment with the RBC loaded enzymes.
      From these data, an innovative, novel method for encapsulating proteins into
      intact and fully functional erythrocytes was established for potential treatment
      of ALL.

PMID- 19577602
TI  - Clematis montana lectin, a novel mannose-binding lectin from traditional Chinese
      medicine with antiviral and apoptosis-inducing activities.
AB  - A novel mannose-binding lectin (designated CML) was isolated from Clematis
      montana Buch.-Ham stem (Ranunculaceae) using ion exchange and gel filtration
      chromatographies on DEAE-Sepharose and Sephacryl S-100. The purified C. montana
      lectin was a homodimer of 11,968.9 Da subunits as determined by gel filtration
      and MS. The hemagglutinating activity of CML was inhibited by branched
      oligomannosides. The N-terminal 15-amino acid sequence of CML, DNVKYSGQVKNTGSA,
      has not been reported for other lectins. Also, the peptide mass fingerprinting
      assay confirmed that there is no match result of similar plant lectins for CML,
      indicating CML may be a novel plant lectin. CML showed marked antiviral activity
      against various viruses in cell culture. Subsequently, CML was also found to
      exhibit remarkable inhibitory effect on L929, HeLa, MCF7 and HepG2 cells.
      Furthermore, CML specially induced L929 cell apoptosis in dose-dependent manner
      as evidenced by MTT, fluorescent microscopy, LDH activity-based cytotoxicity
      assays and DNA ladder. Moreover, due to both caspase inhibitors and Western blot
      analyses, caspase was also found to play the important role in the potential
      apoptotic mechanism of CML. When the carbohydrate-binding site was fully
      inhibited by sugars, cytotoxicity was abruptly decreased and apoptotic phenomenon
      in L929 cells was not observed, suggesting a significant correlation between
      mannose-binding-specific activity and the antineoplastic mechanism.

PMID- 19577603
TI  - Angiotensin-(1-7) antagonist, A-779, microinjection into the caudal ventrolateral
      medulla of renovascular hypertensive rats restores baroreflex bradycardia.
AB  - In the present study we evaluated the effect of caudal ventrolateral medulla
      (CVLM) microinjection of the main angiotensin (Ang) peptides, Ang II and Ang-(1
      7), and their selective antagonists on baseline arterial pressure (AP) and on
      baroreceptor-mediated bradycardia in renovascular hypertensive rats (2K1C).
      Microinjection of Ang II and Ang-(1-7) into the CVLM of 2K1C rats produced
      similar decrease in AP as observed in Sham rats. In both Sham and 2K1C, the
      hypotensive effect of Ang II and Ang-(1-7) at the CVLM was blocked, for up to 30
      min, by previous CVLM microinjection of the Ang II AT1 receptor antagonist,
      Losartan, and Ang-(1-7) Mas antagonist, A-779, respectively. As expected, the
      baroreflex bradycardia was lower in 2K1C in comparison to Sham rats. CVLM
      microinjection of A-779 improved the sensitivity of baroreflex bradycardia in
      2K1C hypertensive rats. In contrast, Losartan had no effect on the baroreflex
      bradycardia in either 2K1C or Sham rats. These results suggest that Ang-(1-7) at
      the CVLM may contribute to the low sensitivity of the baroreflex control of heart
      rate in renovascular hypertensive rats.

PMID- 19577604
TI  - Ghrelin receptor agonist, GHRP-2, attenuates burn injury-induced MuRF-1 and MAFbx
      expression and muscle proteolysis in rats.
AB  - Thermal injury results in hypermetabolism, loss of body weight, and skeletal
      muscle wasting in mice and rats. Our earlier studies have demonstrated that
      ghrelin injection stimulates food intake and growth hormone release and inhibits
      skeletal muscle proteolysis in rats with thermal injury. We sought to develop a
      lower molecular weight, stable and longer acting peptide to combat the catabolic
      responses caused by thermal injury. Towards this goal, we examined the role of
      the hexapeptide mimetic of ghrelin, growth hormone-releasing peptide-2 (GHRP-2),
      on expression of E3 ubiquitin ligases and breakdown of muscle protein in rats
      with thermal injury. Slow in vivo release of GHRP-2 through minipump for 24h
      attenuated the thermal injury-induced increase in mRNA expression of IL-6 and of
      the E3 ubiquitin ligases, MuRF-1 and MAFbx, in rat skeletal muscle. Furthermore,
      burn-induced increases in total and myofibrillar protein breakdown from rat EDL
      muscle were attenuated by GHRP-2. These findings suggest that catabolic responses
      resulting from thermal injury can be attenuated by GHRP-2.

PMID- 19577605
TI  - Influence of Indole-3-butyric acid on antioxidant defense systems in various
      tissues of rats at subacute and subchronic exposure.
AB  - This study was carried out to investigate the effects of Indole-3-butyric acid
      (IBA), a plant growth regulator (PGR), on antioxidant defense systems (ADS) such
      as reduced glutathione (GSH) level and Glutathione-S-transferase (GST),
      glutathione peroxidase (GSH-Px) superoxide dismutase (SOD) enzymes activity in
      various tissues of rats exposed to 25 and 50 ppm dosages of IBA for 20 and 45
      days. Results showed that the administrations of IBA fluctuated GSH levels in
      some tissues of rats treated with both dosages and periods. With regard to the
      ADS enzymes, SOD and GST activities increased significantly in the most of the
      tissues in rats treated with both dosages and periods of IBA. Also, GSH-Px
      activity fluctuated after subacute and subchronic exposure with both dosages in
      some of the tissues in rats compared to that the control rats. The observations
      presented led us to conclude that the administrations of IBA at subacute and
      subchronic affected the ADS system in various tissues of rats. This may reflect
      the potential role of these parameters as useful biomarkers for toxicity of IBA.

PMID- 19577606
TI  - Minimum tolerable exposure period and maximum threshold dietary intake of
      ochratoxin A for causing renal cancer in male Dark Agouti rats.
AB  - In rats fed dietary ochratoxin A (5 ppm for 3, 6 or 9 months) no renal tumours
      occurred throughout natural life of the group treated for 3 months, during which
      the ochratoxin dose was 3 times that in the high dose group of the NTP study.
      Bilateral renal carcinoma occurred in one rat in the 6 month group. Four rats
      treated for 9 months developed unilateral renal carcinoma. Overall latency
      between ceasing toxin exposure and discovering tumours was 35-97 weeks.
      Experimental verification of a 'no observable effect level' was made for feed
      containing 400 ppb, equivalent to approximately 7 microg ochratoxin A/day for
      Dark Agouti rats for up to 2 years, during which mean daily dose commenced at
      approximately 50 microg/kg, but later for adults was in the range 30-20
      microg/kg. This data doubles the daily in vivo threshold dose from the NTP study
      ( approximately 15 microg/kg), and could influence human risk assessment. An at
      least 3 month threshold period for exposure to exceptionally high daily OTA
      intake (90 microg; 640-450 microg/kg) raises doubts over interpretation of
      experimental molecular data for OTA exposure at lower dose for up to 3 months in
      studies aimed at understanding carcinogenic mechanism.

PMID- 19577607
TI  - Cytoprotective activity of amifostine on cultured human lymphocytes exposed to
      irinotecan.
AB  - Irinotecan (camptothecin, CAM) is a topoisomerase-I inhibitor with a well
      established action in the chemotherapy of colorectal and ovarian cancer.
      Hematological and intestinal toxicity are commonly noted in patients treated with
      CAM. In this study, we examined the cytoprotective efficacy of amifostine
      (ethyol, ETH) against chromosomal damage induced by this drug on cultured
      peripheral human lymphocytes. Cultured lymphocytes were exposed to CAM (50 and
      100 ng/ml of final concentrations) without or with ETH (in concentrations varying
      between 40 and 800 microg/ml of final culture volume). CAM's genotoxicity was
      quantified by counting the Sister Chromatid Exchange (SCEs) rate. The mitotic
      index (MI) and proliferation rate index (PRI) were also assessed. The SCE rate
      was increased following incubation with CAM, but the combined treatment of CAM
      with ETH significantly reduced the SCE formation, especially when ETH added at
      high concentrations. The MIs and PRIs remained also unaltered in cultures with
      CAM, but MIs were reduced with the combined treatment at high ETH concentrations.
      Clinical studies are required to assess the predicted benefits from ETH in
      patients receiving CAM.

PMID- 19577608
TI  - Effect of methimazole treatment on doxorubicin-induced cardiotoxicity in mice.
AB  - The major limiting factor in long-term administration of doxorubicin is the
      development of cumulative dose-dependent cardiomyopathy and congestive heart
      failure that limit the use of this drug. The present study was undertaken to find
      out the chemo protective role of methimazole against doxorubicin-induced
      cardiotoxicity in experimental animals. In the present study, doxorubicin
      treatment in a dose of 3mg/kg, i.p., every other day for six doses showed a
      significant 2.6-, 3- and 10.5-fold increase in the cardiac enzyme activities CK
      MB and LDH and troponin-I, respectively, in the serum of the animals.
      Histopathological investigation of heart tissues showed swollen muscle fibers
      with interstitial edema and inflammatory exudate. Pretreatment of the animals
      with methimazole at a dose level of 40 mg/kg, i.p., 30 min before doxorubicin,
      returned the cardiac enzyme levels to nearly normal value with partial reversal
      of the inflammatory lesions and the swollen muscle fibers induced by doxorubicin.
      Moreover, methimazole pretreatment, decreased the doxorubicin level in the heart
      tissues with a significant increase in plasma level and non significant effect on
      doxorubicin level in tumor cells. At the same time, methimazole pretreatment did
      not significantly interfere with the antitumor activity of doxorubicin.

PMID- 19577609
TI  - Antihepatotoxic effect of corn peptides against Bacillus Calmette
      Guerin/lipopolysaccharide-induced liver injury in mice.
AB  - Hepatitis is a severe disease with a high incidence rate around the world [Hwang,
      J.M., Tseng, T.H., Tsai, Y.Y., Lee, H.J., Chou, F.P., Wang, C.J., Chu, C.Y.,
      2005. Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic
      toxicity in rat hepatocytes. J. Biomed. Sci. 12, 389-397]. Corn gluten meal is a
      byproduct of starch industry with abundant protein. However, the application of
      corn protein is limited because of its low solubility and short of essential
      amino acids such as lysine and tryptophan. The hepatoprotective activity of corn
      peptides (CP) from corn gluten meal hydrolysate was evaluated against Bacillus
      Calmette-Guerin (BCG)/lipopolysaccharide (LPS) induced immunological liver injury
      (ILI) in mice. Results showed that ILI was manifested by a significant increase
      in levels of serum aspartate aminotransferase (AST)/alanine aminotransferase
      (ALT) and liver malondialdehyde (MDA)/nitric oxide (NO) levels (p<0.01), and by a
      significant decrease in levels of superoxide dismutase (SOD)/glutathione
      peroxidase (GPX) and glutathione (GSH) in liver (p<0.01). Pretreatment of mice
      with CP reversed these altered parameters to normal values. The effect of CP was
      further demonstrated by histopathological examination of liver sections. The best
      hepatoprotective effect of CP treatment was observed at the dose of 600 mg/kg bw,
      which was evidenced from biochemical parameters and liver histopathological
      characters. Results of this study revealed that CP could afford a significant
      protection against BCG/LPS-induced hepatocellular injury. It will broaden the
      application and increase the value of corn gluten meal, byproduct from starch
      industry.

PMID- 19577610
TI  - Ethylacetate extract from Draconis Resina inhibits LPS-induced inflammatory
      responses in vascular smooth muscle cells and macrophages via suppression of ROS
      production.
AB  - Draconis Resina (DR) is a type of dragon's blood resin obtained from Daemomorops
      draco BL. (Palmae). DR has long been used as a traditional Korean herbal
      medicine, and is currently used in traditional clinics to treat wounds, tumors,
      diarrhea, and rheumatism, insect bites and other conditions. In this study, we
      evaluated fractionated extracts of DR to determine if they inhibited the
      production of interleukin-1beta (IL-1beta) and the expression of cyclooxygenase
      (COX)-2. The results of this analysis revealed that the ethylacetate extract of
      Draconis Resina (DREA) was more potent than that of other extracts. Moreover,
      DREA inhibited the production of nitric oxide (NO), reactive oxygen species
      (ROS), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), IL-8
      and IL-6 in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells
      (HASMC) and RAW 264.7 macrophages. Furthermore, treatment with an NADPH oxidase
      assembly inhibitor, AEBSF, efficiently blocked LPS-induced mitogen-activated
      protein kinases (MAPKs) activation, as did DREA. These findings indicate that
      DREA inhibits the production of NO, PGE(2), TNF-alpha, IL-8, and IL-6 by LPS via
      the inhibition of ROS production, which demonstrates that DREA inhibits LPS
      induced inflammatory responses via the suppression of ROS production. Taken
      together, these results indicate that DREA has the potential for use as an anti
      atherosclerosis agent.

PMID- 19577611
TI  - Impact of acute psychosocial stress on peripheral blood gene expression pathways
      in healthy men.
AB  - We investigated peripheral blood mononuclear cell gene expression responses to
      acute psychosocial stress to identify molecular pathways relevant to the stress
      response. Blood samples were obtained from 10 healthy male subjects before,
      during and after (at 0, 30, and 60 min) a standardized psychosocial laboratory
      stressor. Ribonucleic acid (RNA) was extracted and gene expression measured by
      hybridization to a 20,000-gene microarray. Gene Set Expression Comparisons (GSEC)
      using defined pathways were used for the analysis. Forty-nine pathways were
      significantly changed from baseline to immediately after the stressor (p<0.05),
      implicating cell cycle, cell signaling, adhesion and immune responses. The
      comparison between stress and recovery (measured 30 min later) identified 36
      pathways, several involving stress-responsive signaling cascades and cellular
      defense mechanisms. These results have relevance for understanding molecular
      mechanisms of the physiological stress response, and might be used to further
      study adverse health outcomes of psychosocial stress.

PMID- 19577612
TI  - Di-codon usage for classification of genes.
AB  - Genes are often classified into biologically related groups so that inferences on
      their functions can be made. This paper demonstrates that the di-codon usage is a
      useful feature for gene classification and gives better classification accuracy
      than the codon usage. Our experiments with different classifiers show that
      support vector machines performs better than other classifiers in classifying
      genes by using di-codon usage as features. The method is illustrated on 1841 HLA
      sequences which are classified into two major classes, HLA-I and HLA-II, and
      further classified into the subclasses of major classes. By using both codon and
      di-codon features, we show near perfect accuracies in the classification of HLA
      molecules into major classes and their sub-classes.

PMID- 19577613
TI  - On the evolution of scale-free topologies with a gene regulatory network model.
AB  - A novel approach to generating scale-free network topologies is introduced, based
      on an existing artificial gene regulatory network model. From this model,
      different interaction networks can be extracted, based on an activation
      threshold. By using an evolutionary computation approach, the model is allowed to
      evolve, in order to reach specific network statistical measures. The results
      obtained show that, when the model uses a duplication and divergence
      initialisation, such as seen in nature, the resulting regulation networks not
      only are closer in topology to scale-free networks, but also require only a few
      evolutionary cycles to achieve a satisfactory error value.

PMID- 19577614
TI  - Mouse carnitine-acylcarnitine translocase (CACT) is transcriptionally regulated
      by PPARalpha and PPARdelta in liver cells.
AB  - BACKGROUND: Hepatic PPARalpha acts as the primary mediator of the adaptive
      response to fasting by upregulation of a number of genes involved in fatty acid
      catabolism. Whether carnitine-acylcarnitine translocase (CACT), which mediates
      the import of acylcarnitines into the mitochondrial matrix for subsequent beta
      oxidation of fatty acid moieties, is also regulated by PPARalpha in the liver has
      not yet been investigated. METHODS AND RESULTS: Herein, we observed that hepatic
      mRNA abundance of CACT was increased by both, fasting and treatment with
      PPARalpha agonist WY-14,643 in wild-type mice but not PPARalpha-knockout mice
      (P<0.05). Cell culture experiments revealed that CACT mRNA abundance was higher
      in liver cells treated with either WY-14,643 or PPARdelta agonist GW0742, but not
      with PPARgamma agonist troglitazone (TGZ) than in control cells (P<0.05). In
      addition, reporter assays revealed activation of mouse CACT promoter by WY-14,643
      and GW0742, but not TGZ. Moreover, deletion and mutation analyses of CACT
      promoter and 5'-UTR revealed one functional PPRE in the 5'-UTR of mouse CACT.
      GENERAL SIGNIFICANCE: CACT is upregulated by PPARalpha and PPARdelta, probably by
      binding to a functional PPRE at position +45 to +57 relative to the transcription
      start site. The upregulation of CACT by PPARalpha and PPARdelta, which are both
      important for the regulation of fatty acid oxidation in tissues during fasting,
      may increase the import of acylcarnitine into the mitochondrial matrix during
      fasting.

PMID- 19577615
TI  - bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression
      and modulates the migration capacity of fibrosarcoma cells.
AB  - BACKGROUND: Hyaluronan (HA) a glycosaminoglycan, is capable of transmitting
      extracellular matrix derived signals to regulate cellular functions. In this
      study, we investigated whether the changes in HT1080 and B6FS fibrosarcoma cell
      lines HA metabolism induced by basic fibroblast growth factor (bFGF) are
      correlated to their migration. METHODS: Real-time PCR, in vitro wound healing
      assay, siRNA transfection, enzyme digestions, western blotting and
      immunofluorescence were utilized. RESULTS: bFGF inhibited the degradation of HA
      by decreasing hyaluronidase-2 expression in HT1080 cells (p=0.0028), increased HA
      synthase-1 and -2 expression as we previously found and enhanced high molecular
      weight HA deposition in the pericellular matrix. Increased endogenous HA
      production (p=0.0022) and treatment with exogenous high molecular weight HA
      (p=0.0268) correlated with a significant decrease of HT1080 cell migration
      capacity. Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized
      high molecular weight HA regulates HT1080 cell motility. Induced degradation of
      the HA content by hyaluronidase treatment and addition of low molecular weight
      HA, resulted in a significant stimulation of HT1080 cells' motility (p<0.01). In
      contrast, no effects on B6FS fibrosarcoma cell motility were observed.
      CONCLUSIONS: bFGF regulates, in a cell-specific manner the migration capability
      of fibrosarcoma cells by modulating their HA metabolism. HA metabolism is
      suggested to be a potential therapeutic target in fibrosarcoma.

PMID- 19577616
TI  - Marsupial-specific microRNAs evolved from marsupial-specific transposable
      elements.
AB  - Using a direct miRNA cloning strategy we previously identified fourteen marsupial
      or species-specific microRNAs in the marsupial species Monodelphis domestica. In
      the present study we examined each of the pre-miRNAs and their flanking sequences
      and demonstrate that half of these miRNAs evolved from marsupial-specific
      transposable elements. These findings reinforce the view that transposable
      elements are a previously unappreciated source of new, lineage-specific
      microRNAs.

PMID- 19577617
TI  - A novel NADPH-dependent aldehyde reductase gene from Saccharomyces cerevisiae
      NRRL Y-12632 involved in the detoxification of aldehyde inhibitors derived from
      lignocellulosic biomass conversion.
AB  - Aldehyde inhibitors such as furfural, 5-hydroxymethylfurfural, anisaldehyde,
      benzaldehyde, cinnamaldehyde, and phenylaldehyde are commonly generated during
      lignocellulosic biomass conversion process for low-cost cellulosic ethanol
      production that interferes with subsequent microbial growth and fermentation. In
      situ detoxification of the aldehyde inhibitors is possible by the tolerant
      ethanologenic yeast that involves multiple genes including numerous functional
      reductases. In this study, we report a novel aldehyde reductase gene clone Y63
      from ethanologenic yeast Saccharomyces cerevisiae NRRL Y12632, representing the
      uncharacterized ORF YGL157W, which demonstrated NADPH-dependent reduction
      activities toward at least 14 aldehyde substrates. The identity of gene clone Y63
      is the same with YGL157W of SGD since a variation of only 35 nucleotides in
      genomic sequence and three amino acid residues were observed between the two that
      share the same length of 347 residues in size. As one among the highly induced
      genes, YGL157W of Y-12632 showed significantly high levels of transcript
      abundance in response to furfural and HMF challenges. Based on the deduced amino
      acid sequence and the most conserved functional motif analyses including closely
      related reductases from five other yeast species to this date, YGL157W was
      identified as a member of the subclass 'intermediate' of the SDR (short-chain
      dehydrogenase/reductase) superfamily with the following typical characteristics:
      the most conserved catalytic site to lie at Tyr(169)-X-X-X-Lys(173); an
      indispensable reduction catalytic triad at Ser(131), Tyr(169), and Lys(173), and
      an approved cofactor-binding motif at Gly(11)-X-X-Gly(14)-X-X-Ala(17) near the N
      terminus. YGL039W, YDR541C, and YOL151W (GRE2) appeared to be the similar type of
      enzymes falling into the same category of the intermediate subfamily.

PMID- 19577618
TI  - Endogenous retroviral LTRs as promoters for human genes: a critical assessment.
AB  - Gene regulatory changes are thought to be major factors driving species
      evolution, with creation of new regulatory regions likely being instrumental in
      contributing to diversity among vertebrates. There is growing appreciation for
      the role of transposable elements (TEs) in gene regulation and, indeed,
      laboratory investigations have confirmed many specific examples of mammalian
      genes regulated by promoters donated by endogenous retroviruses (ERVs) or other
      TEs. Bioinformatics studies have revealed hundreds of additional instances where
      this is likely to be the case. Since the long terminal repeats (LTRs) of
      retroviruses naturally contain abundant transcriptional regulatory signals, roles
      for ERV LTRs in regulating mammalian genes are eminently plausible. Moreover, it
      seems reasonable that exaptation of an LTR regulatory module provides
      opportunities for evolution of new gene regulatory patterns. In this Review we
      summarize known examples of LTRs that function as human gene alternative
      promoters, as well as the evidence that LTR exaptation has resulted in a pattern
      of novel gene expression significantly different from the pattern before LTR
      insertion or from that of gene orthologs lacking the LTR. Available data suggest
      that, while new expression patterns can arise as a result of LTR usage, this
      situation is relatively rare and is largely restricted to the placenta. In many
      cases, the LTR appears to be a minor, alternative promoter with an expression
      pattern similar to that of the native promoter(s) and hence likely exerts a
      subtle overall effect on gene expression. We discuss these findings and offer
      evolutionary models to explain these trends.

PMID- 19577619
TI  - Ethylendiamine core PAMAM dendrimers/siRNA complexes as in vitro silencing
      agents.
AB  - We have screened the formation of complexes between ethylendiamine (EDA) core
      polyamidoamine (PAMAM) dendrimers (D) and a short interfering RNA (siRNA) as a
      function of three variables: the ionic strength of the medium (lacking or
      containing 150 mM NaCl), the D generation (G4, G5, G6 and G7) and the N/P ratio
      (nitrogen amines in D/phosphate in siRNA). It was observed that all D formed
      complexes with siRNA, being the size of the complexes strictly dependent on the
      ionic strength of the media. The strong electrostatic interactions occurring in
      NaCl lacking medium made siRNA-D complexes (siRNA-D) smaller than those obtained
      in NaCl containing medium (30-130 nm, +25 mV zeta potential vs. several microm
      800 nm, 0 zeta potential, respectively). Not surprisingly, both the uptake and
      inhibition of EGFP expression in cell culture, resulted dependent on siRNA-D
      size. siRNA-D prepared in NaCl containing medium were poorly captured and
      presented a basal activity on phagocytic (J-774-EGFP) cells, being inactive on
      non-phagocytic cells (T98G-EGFP). However, the smaller siRNA-D prepared in NaCl
      lacking medium were massively captured, exhibiting the highest inhibition of EGFP
      expression at 50 nM siRNA (non-cytotoxic concentration). Remarkably, siRNA-G7
      produced the highest inhibition of EGFP expression both in T98G-EGFP (35%) and J
      774-EGFP (45%) cells, in spite of inducing a lower protection of siRNA against
      RNase A degradation. Taken together, our results showed that modifying the
      chemical structure of D is not the only way of achieving siRNA-D suitable for
      silencing activity. The simple use of a low ionic strength preparation media has
      been critical to get small siRNA-D that could be captured by cells and in
      particular, siRNA-G7 but not those formed by lower generation D, possessed
      structural constraints other than size that could favor its silencing activity.

PMID- 19577620
TI  - Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced
      pain in rats.
AB  - To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was
      loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA
      NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat
      formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the
      Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar
      injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic
      activity to typical BV acupuncture during the late phase, compared with saline
      treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was
      also effective in alleviating the edema induced by allergens in bee venom. These
      results indicate that PLGA-encapsulation provided a more prolonged effect of BV
      acupuncture treatment, while maintaining a comparable therapeutic effect.

PMID- 19577621
TI  - Mechanisms of Panax ginseng in preventing rat pheochromocytoma cells from
      apoptosis.
AB  - AIMS OF THE STUDY: Although ginseng root possesses dominant central therapeutic
      effects and has recently undergone investigations for treating different neuronal
      diseases, most of its mechanisms are still unknown. Therefore, the
      neuroprotective mechanisms of ginseng were studied. MATERIALS AND METHODS: The
      protection afforded by different methanol extracts of Panax ginseng (PG) was
      tested in a serum deprivation-induced apoptotic model using neuronal-like
      pheochromocytoma (PC12) cells. An MTT assay, annexin V-FITC staining, and Western
      blots were, respectively, applied to identify the viability of cells, the
      apoptotic form of cell death, and the activity of antiapoptotic signaling.
      RESULTS: The known antiapoptotic PI3-K/Akt and MEK/ERK pathways in this system
      were ruled out due to failure of LY 294002 and PD 98059 to block the protection
      by PG. A protein kinase A (PKA) inhibitor was found to block the protection by PG
      and PG-induced CREB phosphorylation, suggesting that the PKA/CREB pathway
      mediates the protective effect of PG. Downregulation of classical and novel PKCs
      failed to block the protection by PG, while an atypical PKC inhibitor blocked
      protection by PG. CONCLUSIONS: PKA and atypical PKC are important for the
      protection afforded by PG in preventing serum deprivation-induced PC12 cell
      apoptosis.

PMID- 19577623
TI  - Gomisin A induces Ca2+-dependent activation of eNOS in human coronary artery
      endothelial cells.
AB  - AIM OF THE STUDY: Gomisin A (GA) is a small molecular weight lignan contained in
      Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used
      as a tonic in traditional Korean medicine. We previously demonstrated that GA
      induces endothelium-dependent and -independent relaxation in rat thoracic aorta,
      however the signaling pathways involved was not clarified. In this study, we
      examined whether GA could actually induce nitric oxide (NO) production and
      clarified the mechanism in cultured human coronary artery endothelial cells
      (HCAEC). RESULTS: Treatment of HCAEC with GA induced NO production in a time- and
      concentration-dependent manner in association with an enhanced endothelial NO
      synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both
      GA-induced NO production and eNOS activation were attenuated by pretreatment of
      the cells with EGTA, an extracellular Ca(2+) chelator, and BAPTA-AM, an
      intracellular Ca(2+) chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor,
      suggesting involvement of Ca(2+). Furthermore, GA rapidly increased the
      intracellular Ca(2+) concentration, which was abolished in Ca(2+) free media.
      CONCLUSION: Taken together, our results suggest that GA induces Ca(2+)-dependent
      activation and translocation of eNOS in HCAEC, events linked to NO production and
      thereby endothelial-dependent vasorelaxation.

PMID- 19577622
TI  - Antiplasmodial activity of Punica granatum L. fruit rind.
AB  - AIM OF THE STUDY: Sun-dried rind of the immature fruit of Punica granatum L.
      (Punicaceae) (Pg) is presently used as a herbal formulation (OMARIA) in Orissa,
      India, for the therapy and prophylaxis of malaria. The aims of this study were
      (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of
      a tannin enriched fraction and of compounds/metabolites of the antimalarial
      plant, (ii) to estimate the curative efficacy of the Pg extracts and (iii) to
      explore the mechanism of action of the antiplasmodial compounds. Urolithins, the
      ellagitannin metabolites, were also investigated for antiplasmodial activity.
      MATERIALS AND METHODS: Chloroquine-susceptible (D10) and -resistant (W2) strains
      of Pf were used for in vitro studies and the rodent malaria model Plasmodium
      berghei-BALB/c mice was used for in vivo assessments. Recombinant plasmepsins 2
      and 4 were used to investigate the interference of Pg compounds with the
      metabolism of haemoglobin by malaria parasites. RESULTS: The Pg methanolic
      extract (Pg-MeOH) inhibited parasite growth in vitro with a IC(50) of 4.5 and 2.8
      microg/ml, for D10 and W2 strain, respectively. The activity was found to be
      associated to the fraction enriched with tannins (Pg-FET, IC(50) 2.9 and 1.5
      microg/ml) in which punicalagins (29.1%), punicalins, ellagic acid (13.4%) and
      its glycoside could be identified. Plasmepsin 2 was inhibited by Pg-MeOH extract
      and by Pg-FET (IC(50) 7.3 and 3.0 microg/ml), which could partly explain the
      antiparasitic effect. On the contrary, urolithins were inactive. Both Pg-MeOH
      extract and Pg-FET did not show any in vivo efficacy in the murine model.
      CONCLUSIONS: The in vitro studies support the use of Pg as antimalarial remedy.
      Possible explanations for the negative in vivo results are discussed.

PMID- 19577624
TI  - Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum
      trilobum in a cell screening assay.
AB  - AIM OF THE STUDY: The purpose of the study was to assess the anti-inflammatory
      effects of the mushroom Inonotus obliquus (Chaga), Polygala senega (Senega) and
      Viburnum trilobum (Cranberry) bark extract fractions from locally produced
      materials in lipopolysaccharide (LPS) induced murine macrophage RAW 164.7 cells.
      MATERIALS AND METHODS: Four fractions from each of the three extracts were
      obtained: (80% ethanol extracted; Fa), (water-soluble polysaccharide fraction;
      Fb), (Polyphenolic fraction; Fc) and (ETOAc/H(2)O extracted fraction; Fd). These
      extract fractions were tested in the cell screening system at 50,100 and 500
      microg/ml for their ability to inhibit LPS induced inflammatory cytokines IL
      1beta, TNFalpha and IL-6. Supernatants from LPS alone treated cells were used as
      control. The cytokines in the cell culture supernatants following treatments with
      extract fractions were quantified by ELISA method, using 96 well ELISA plates.
      RESULTS: All fractions of the extracts significantly inhibited (p<0.05) the
      levels of IL-1beta, IL-6 and TNFalpha except the polyphenolic Fc fraction of
      Senega which showed an increased production of IL-6. Furthermore, each fraction
      showed a dose-dependant anti-inflammatory effect. Nitric oxide production was not
      affected by cranberry and senega, while Chaga significantly reduced NO production
      in murine macrophage cell assay. CONCLUSIONS: These results demonstrate that the
      extracts obtained from the root of Polygala senega L., bark of Viburnum trilobum,
      and the mushroom Inonotus obliquus possess anti-inflammatory properties when
      tested in a RAW 264.7 macrophage cell system.

PMID- 19577625
TI  - Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS
      activated RAW 264.7 macrophages.
AB  - AIM OF THE STUDY: The root of Scutellaria baicalensis Georgi (Labiatae), also
      known as Scutellariae Radix, possesses anticancer, antiviral, and anti
      inflammatory properties. And it is one of the most widespread herbal remedies
      used in Oriental medicine. In the present study, we investigated the effects of
      Scutellariae Radix water extract (SR) on proinflammatory mediators secreted from
      lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIAL AND METHODS:
      Cell viability was assessed by MTT assay and nitric oxide (NO) concentration in
      the cultured medium was determined by the Griess reaction. Various Cytokines
      released from LPS-induced Raw 264.7 cells were measured in the cell culture
      supernatants using a multiplex bead array assay based on xMAP technology.
      RESULTS: We found that SR significantly inhibited the production of NO,
      interleukin (IL)-3, IL-6, IL-10, IL-12p40, IL-17, interferon-inducible protein
      (IP)-10, keratinocyte-derived chemokine (KC), and vascular endothelial growth
      factor (VEGF) in LPS-induced RAW 264.7 cells at the concentrations of 25, 50,
      100, 200 microg/ml (p<0.05). CONCLUSIONS: These results suggest that SR has anti
      inflammatory activity related with its inhibition of NO, cytokine, chemokine, and
      growth factor production in macrophages.

PMID- 19577626
TI  - Modeling cellulase kinetics on lignocellulosic substrates.
AB  - The enzymatic hydrolysis of cellulose to glucose by cellulases is one of the
      major steps involved in the conversion of lignocellulosic biomass to yield
      biofuel. This hydrolysis by cellulases, a heterogeneous reaction, currently
      suffers from some major limitations, most importantly a dramatic rate slowdown at
      high degrees of conversion. To render the process economically viable, increases
      in hydrolysis rates and yields are necessary and require improvement both in
      enzymes (via protein engineering) and processing, i.e. optimization of reaction
      conditions, reactor design, enzyme and substrate cocktail compositions, enzyme
      recycling and recovery strategies. Advances in both areas in turn strongly depend
      on the progress in the accurate quantification of substrate-enzyme interactions
      and causes for the rate slowdown. The past five years have seen a significant
      increase in the number of studies on the kinetics of the enzymatic hydrolysis of
      cellulose. This review provides an overview of the models published thus far,
      classifies and tabulates these models, and presents an analysis of their basic
      assumptions. While the exact mechanism of cellulases on lignocellulosic biomass
      is not completely understood yet, models in the literature have elucidated
      various factors affecting the enzymatic rates and activities. Different
      assumptions regarding rate-limiting factors and basic substrate-enzyme
      interactions were employed to develop and validate these models. However, the
      models need to be further tested against additional experimental data to validate
      or disprove any underlying hypothesis. It should also provide better insight on
      additional parameters required in the case that more substrate and enzyme
      properties are to be included in a model.

PMID- 19577627
TI  - Yeast flocculation: New story in fuel ethanol production.
AB  - Yeast flocculation has been used in the brewing industry to facilitate biomass
      recovery for a long time, and thus its mechanism of yeast flocculation has been
      intensively studied. However, the application of flocculating yeast in ethanol
      production garnered attention mainly in the 1980s and 1990s. In this article,
      updated research progress in the molecular mechanism of yeast flocculation and
      the impact of environmental conditions on yeast flocculation are reviewed.
      Construction of flocculating yeast strains by genetic approach and utilization of
      yeast flocculation for ethanol production from various feedstocks were presented.
      The concept of self-immobilized yeast cells through their flocculation is
      revisited through a case study of continuous ethanol fermentation with the
      flocculating yeast SPSC01, and their technical and economic advantages are
      highlighted by comparing with yeast cells immobilized with supporting materials
      and regular free yeast cells as well. Taking the flocculating yeast SPSC01 as an
      example, the ethanol tolerance of the flocculating yeast was also discussed.

PMID- 19577628
TI  - Mechanisms in the serotype-independent pneumococcal immunity induced in mice by
      intranasal vaccination with the cell wall polysaccharide.
AB  - We previously reported that cell wall polysaccharide (CWPS) given to mice
      intranasally with adjuvant induces serotype-independent immunity to pneumococci.
      Some strains make CWPS with one phosphocholine group (CWPS/1), but most express
      two per tetrasaccharide repeat unit (CWPS/2). Here, CWPS/1 and CWPS/2 were
      equally protective against colonization by CWPS/2-type pneumococci, but the
      related Streptococcus mitis polymer lacking phosphocholine was non-protective.
      Previously the protection was shown to be CD4+T cell-dependent, abrogated by
      antiserum to interleukin (IL)-17A, and demonstrable in antibody-defective mice.
      Here, CWPS failed to protect IL-17A receptor knockout mice, further indicating IL
      17A-dependence. When commercial CWPS/1 was size-fractionated preparatively, the
      larger exceeded the smaller molecules in their capacity to prime for IL-17A
      responses, and only the larger protected against pneumococcal colonization.
      However, a CWPS-tetanus toxoid conjugate - despite raising high titers of
      phosphocholine antibody - was non-protective, confirming the irrelevance of
      humoral immunity in this model. The results strengthen the concept that IL-17A
      mediated T cell immunity is inducible by zwitterionic polysaccharides with
      sufficient chain length to provide coiled secondary structure. Coupling CWPS to
      protein, which paradoxically prevents protection, may occlude this regular linear
      conformation. We suggest that mucosal immunization with CWPS primes T(H)17 cells,
      which - upon contact with the phosphocholine of colonizing pneumococci -
      elaborate IL-17A, enhancing phagocytosis.

PMID- 19577629
TI  - Transepidermal water loss for probing full-thickness skin barrier function:
      correlation with tritiated water flux, sensitivity to punctures and diverse
      surfactant exposures.
AB  - Skin barrier function is a key parameter to consider when performing in vitro
      percutaneous absorption studies. Whilst tritiated water flux measurements were
      often used to assess skin integrity, recent decades have witnessed the emergence
      of the more rapid and user-friendly transepidermal water loss (TEWL) approach.
      Yet to date, the nature of the correlation between TEWL and skin barrier function
      in vitro has still not been comprehensively established. In this study, a novel
      TEWL device, operating on a cold-induced vapour sink principle, was used to probe
      the barrier function of full-thickness porcine skin. The method was sufficiently
      sensitive to show the influence of punctures on barrier function although the
      observed non-linear pattern suggested tissue swelling processes and/or capillary
      action could be occurring. The results of various surfactant application
      experiments strongly suggested that TEWL was indeed largely predictive of skin
      sample integrity. A key finding was that basal TEWL was linearly correlated with
      basal tritiated water flux (r(2)=0.80, n=63). Thus, a dedicated TEWL method can
      be used as a good alternative to water flux measurements for assessing full
      thickness skin barrier function.

PMID- 19577631
TI  - Developmental toxicity of brominated flame retardants, tetrabromobisphenol A and
      1,2,5,6,9,10-hexabromocyclododecane, in rat offspring after maternal exposure
      from mid-gestation through lactation.
AB  - To evaluate developmental exposure effects of two brominated flame retardants,
      tetrabromobisphenol A (TBBPA) and 1,2,5,6,9,10-hexabromocyclododecane (HBCD),
      pregnant Sprague-Dawley rats were administered either chemical at doses of 100,
      1000 or 10,000 ppm in a soy-free diet from gestation day 10 until the day 20
      after delivery. Offspring exposed to TBBPA showed dose-unrelated slight decreases
      of serum triiodothyronine (T(3)) concentration at postnatal day 20, and there was
      no evidence of hypothyroidism-related neuronal mismigration and impaired
      oligodendroglial development as judged by morphometric analyses of NeuN
      immunoreactive neuronal distribution in the hippocampal CA1, and area of corpus
      callosum as well as density of 2',3'-cyclic nucleotide 3'-phosphodiesterase
      (CNPase)-immunoreactive oligodendrocytes in the cingulate deep cortex at the
      adult stage. On the other hand, HBCD exerted a weak hypothyroidism evident with
      increases in thyroid weight, thyroid follicular cell hypertrophy and serum
      concentrations of thyroid-stimulating hormone as well as decreases of serum T(3)
      concentrations in offspring at 10,000 ppm at weaning. Increased thyroid weights
      and decreased serum T(3) concentrations were also observed in the adult stage
      from 1000 ppm. With regard to the effect on brain development, HBCD reduced
      density of CNPase-positive oligodendrocytes at 10,000 ppm, suggesting an impaired
      oligodendroglial development. Results thus suggest that TBBPA did not exert
      developmental brain effects, while HBCD did, and 100 ppm was determined to be the
      no-observed-adverse-effect level of HBCD from changes in thyroid parameters at
      the adult stage by maternal exposure, translating into 8.1-21.3mg/kg-d.

PMID- 19577630
TI  - LPS-induced indoleamine 2,3-dioxygenase is regulated in an interferon-gamma
      independent manner by a JNK signaling pathway in primary murine microglia.
AB  - Inflammation-induced activation of the tryptophan catabolizing enzyme indoleamine
      2,3-dioxygenase (IDO) causes depressive-like behavior in mice following acute
      activation of the innate immune system by lipopolysaccharide (LPS). Here we
      investigated the mechanism of IDO expression induced by LPS in primary cultures
      of microglia derived from neonatal C57BL/6J mice. LPS (10 ng/ml) induced IDO
      transcripts that peaked at 8h and enzymatic activity at 24h, resulting in an
      increase in extracellular kynurenine, the catabolic product of IDO-induced
      tryptophan catabolism. This IDO induction by LPS was accompanied by synthesis and
      secretion of the proinflammatory cytokines TNFalpha and IL-6, but without
      detectable IFNgamma expression. To explore the mechanism of LPS-induced IDO
      expression, microglia were pretreated with the c-Jun-N-terminal kinase (JNK)
      inhibitor SP600125 for 30 min before LPS treatment. We found that SP600125
      blocked JNK phosphorylation and significantly decreased IDO expression induced by
      LPS, which was accompanied by a reduction of LPS-induced expression of TNFalpha
      and IL-6. Collectively, these data extend to microglia the property that LPS
      induces IDO expression via an IFNgamma-independent mechanism that depends upon
      activation of JNK. Inhibition of the JNK pathway may provide a new therapy for
      inflammatory depression.

PMID- 19577633
TI  - Effects of in utero exposure to di-n-hexyl phthalate on the reproductive
      development of the male rat.
AB  - Recently, the plasticizer di-n-hexyl phthalate (DnHP) has been demonstrated to be
      teratogenic and adversely affect the reproductive tract in male rat fetuses. This
      study was undertaken to determine the long-term effects of an in utero exposure
      to DnHP on the reproductive development of the male offspring. Di-2-ethylhexyl
      phthalate (DEHP), another phthalate ester known to disrupt the androgen-dependent
      sexual differentiation in the male rat, was used as a positive control. Pregnant
      Sprague-Dawley rats were administered DnHP or DEHP, by gavage on gestation Days
      12-21, at doses of 0, 50, 125, 250, or 500 mg DnHP/kg-d and 500 mg DEHP/kg-d.
      DnHP had no significant effect on maternal body weight gain and pup weights
      during lactation. The proportion of live pups on postnatal day 1 was slightly,
      but not significantly, lower than control at 250 and 500 mg DnHP/kg-d. Male
      offspring displayed reduced anogenital distance on postnatal day 1 (PND) at 125
      mg DnHP/kg-d and above, and areola/nipple retention before weaning and at
      adulthood at 250 and 500 mg DnHP/kg-d. At necropsy on PND 70-78 or PND 111-120,
      severe malformations of the reproductive tract were observed in young adult males
      at 125 mg DnHP/kg-d and higher doses. They mainly consisted of hypospadias,
      underdeveloped testis, and undescended testis. Additionally, histopathological
      examination revealed seminiferous tubule degeneration at the two high doses. Our
      results showed that prenatal exposure to DnHP caused permanent and dose-related
      alterations of the male rat reproductive development, with a similar profile as
      DEHP.

PMID- 19577632
TI  - Neonatal exposure to bisphenol A alters estrogen-dependent mechanisms governing
      sexual behavior in the adult female rat.
AB  - This study examines the effects of neonatal exposure to the endocrine disruptor
      bisphenol A (BPA) on the hypothalamic circuitry controlling the female sexual
      behaviors of adult rats. From postnatal day 1 (PND1) to PND7, pups were injected
      with corn oil (control) or BPA (BPA20: 20mg/kg-d; BPA.05: 0.05 mg/kg-d) and at
      PND85 the rats were bilaterally ovariectomized (OVX). At PND100, OVX-rats
      received estradiol alone or estradiol and progesterone to evaluate estrogen
      dependent gene expression in the hypothalamus and sexual behavior. In BPA-exposed
      females, estrogen receptor alpha (ER alpha) expression was down-regulated in both
      the medial preoptic (MPN) and ventromedial nucleus (VMHvl), while repressor of
      estrogen receptor activity (REA) expression was up-regulated in the VMHvl.
      Interestingly, BPA-exposed females displayed significantly lower levels of
      proceptive behavior. Our results show that BPA permanently alters the
      hypothalamic estrogen-dependent mechanisms that govern sexual behavior in the
      adult female rat.

PMID- 19577634
TI  - A CASCADE of effects of bisphenol A.

PMID- 19577635
TI  - A methodological approach to scaling up fermentation and primary recovery
      processes to the manufacturing scale for vaccine production.
AB  - As the fermentation process is scaled up, the mass-transfer and nutritional
      requirements are to be maintained in improving antigen yields upon scale-up. A
      methodology is adopted to scale-down the processes at the laboratory level in
      order to further optimize the hydrodynamic and nutritional requirements of the
      bacteria prior to scaling up. For recovery of bacterial proteins, several micro
      filtration techniques are discussed. An optimized process consisting of cross
      flow micro-filtration, homogenization and batch clarification using ion-exchange
      resins is used.

PMID- 19577637
TI  - Comparative analysis of Salmonella enterica serovar Enteritidis mutants with a
      vaccine potential.
AB  - If any new live Salmonella vaccine is introduced in the future, it is quite
      probable that detailed characterisation of its attenuation will be required. In
      this study we therefore compared 34 isogenic mutants of S. Enteritidis in aroA,
      aroD, galE, ssrA, sseA, phoP, rpoS, ompR, htrA, clpP, lon, rfaL, rfaG, rfaC, hfq,
      sodCI, hilA, sipA, avrA, sopB, sopA, sopE, sifA, shdA, fliC, fur, relA, spoT, rel
      spoT, misL, rmbA, STM4258, STM4259 and spvBC genes for their resistance to
      stresses likely to be expected in the host and for their virulence and
      immunogenicity in Balb/C mice. We found that the cold and bile resistances
      essentially did not correlate with the resistances to other stress factors.
      Resistance to acid pH, heat, polymyxin and serum correlated with each other and
      also with the attenuation. When the residual virulence and immunogenicity were
      both considered, mutants in htrA, ompR, aroA, aroD and lon performed the best in
      mice. Furthermore, when a detailed comparison of polymyxin and serum sensitive
      mutants was performed, the serum sensitive mutants were more immunogenic.

PMID- 19577636
TI  - Safety and immunogenicity of a subvirion inactivated influenza A/H5N1 vaccine
      with or without aluminum hydroxide among healthy elderly adults.
AB  - A total of 600 healthy adults > or =65 years were randomized to receive 2
      vaccinations 1 month apart of a subvirion avian influenza A/H5N1 vaccine
      containing 3.75, 7.5, 15, or 45microg of hemagglutinin (HA) with or without
      aluminum hydroxide (AlOH). All formulations were safe. Groups given the vaccine
      with AlOH had more injection site discomfort. Dose-related increases in antibody
      responses were noted after the second vaccination. Antibody responses to the
      vaccine were not enhanced by AlOH at any HA dose level. A microneutralization
      titer > or =40 was observed in 36% and 40% of subjects who received 45microg of
      HA with or without AlOH, respectively.

PMID- 19577638
TI  - Kinetic feasibility of nitroxyl reduction by physiological reductants and
      biological implications.
AB  - Nitroxyl (HNO), the one-electron reduced and protonated congener of nitric oxide
      (NO), is a chemically unique species with potentially important biological
      activity. Although HNO-based pharmaceuticals are currently being considered for
      the treatment of chronic heart failure or stroke/transplant-derived ischemia, the
      chemical events leading to therapeutic responses are not established. The
      interaction of HNO with oxidants results in the well-documented conversion to NO,
      but HNO is expected to be readily reduced as well. Recent thermodynamic
      calculations predict that reduction of HNO is biologically accessible. Herein,
      kinetic analysis suggests that the reactions of HNO with several mechanistically
      distinct reductants are also biologically feasible. Product analysis verified
      that the reductants had in fact been oxidized and that in several instances HNO
      had been converted to hydroxylamine. Moreover, a theoretical analysis suggests
      that in the reaction of HNO with thiol reductants, the pathway producing
      sulfinamide is significantly more favorable than that leading to disulfide.
      Additionally, simultaneous production of HNO and NO yielded a biphasic oxidative
      capacity.

PMID- 19577639
TI  - Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the
      mitochondrial permeability transition and cytochrome c release.
AB  - Cardiolipin oxidation is emerging as an important factor in mitochondrial
      dysfunction as well as in the initial phase of the apoptotic process. We have
      previously shown that exogenously added peroxidized cardiolipin sensitizes
      mitochondria to Ca(2+)-induced mitochondrial permeability transition (MPT) pore
      opening and promotes the release of cytochrome c. In this work, the effects of
      intramitochondrial cardiolipin peroxidation on Ca(2+)-induced MPT and on the
      cytochrome c release from mitochondria were studied. The effects of melatonin, a
      compound known to protect the mitochondria from oxidative damage, on both of
      these processes were also tested. tert-Butylhydroperoxide (t-BuOOH), a lipid
      soluble peroxide that promotes lipid peroxidation, was used to induce
      intramitochondrial cardiolipin peroxidation. Exposure of heart mitochondria to t
      BuOOH resulted in the oxidation of cardiolipin, associated with an increased
      sensitivity of mitochondria to Ca(2+)-induced MPT and with the release of
      cytochrome c from the mitochondria. All these processes were inhibited by
      micromolar concentrations of melatonin. It is proposed that melatonin inhibits
      cardiolipin peroxidation in mitochondria, and this effect seems to be responsible
      for the protection afforded by this agent against the MPT induction and
      cytochrome c release. Thus, manipulating the oxidation sensitivity of cardiolipin
      with melatonin may help to control MPT and cytochrome c release, events
      associated with cell death, and thus, be used for treatment of those disorders
      characterized by mitochondrial cardiolipin oxidation and Ca(2+) overload.

PMID- 19577640
TI  - Oxidative stress in the pathogenesis of psoriasis.
AB  - Psoriasis is a chronic immune-mediated hyperproliferative inflammatory skin
      disease in which a cytokine network concept is well established. Skin is a major
      target of oxidative stress mainly due to reactive oxygen species (ROS)
      originating from the environment and skin metabolism itself. Although endogenous
      antioxidants attenuate the harmful effects of ROS, increased or prolonged
      presence of free radicals can override ROS defense mechanisms and mediate
      numerous cellular responses that contribute to the development of a variety of
      skin disorders, including psoriasis. Regarding psoriasis, antioxidant strategies
      have proven to be beneficial therapeutics. The cellular signaling pathways such
      as mitogen-activated protein kinase/activator protein 1, nuclear factor kappaB,
      and Janus kinase-signal transducers and activators of transcription are known to
      be redox sensitive and proven to be involved in the progress of psoriasis. This
      review summarizes the current knowledge of the role of the redox system in
      regulating these signaling pathways related to the pathogenesis of psoriasis.

PMID- 19577642
TI  - Phospholipase A2 subclasses in acute respiratory distress syndrome.
AB  - Phospholipases A2 (PLA2) catalyse the cleavage of fatty acids esterified at the
      sn-2 position of glycerophospholipids. In acute lung injury-acute respiratory
      distress syndrome (ALI-ARDS) several distinct isoenzymes appear in lung cells and
      fluid. Some are capable to trigger molecular events leading to enhanced
      inflammation and lung damage and others have a role in lung surfactant recycling
      preserving lung function: Secreted forms (groups sPLA2-IIA, -V, -X) can directly
      hydrolyze surfactant phospholipids. Cytosolic PLA2 (cPLA2-IVA) requiring Ca2+ has
      a preference for arachidonate, the precursor of eicosanoids which participate in
      the inflammatory response in the lung. Ca(2+)-independent intracellular PLA2s
      (iPLA2) take part in surfactant phospholipids turnover within alveolar cells.
      Acidic Ca(2+)-independent PLA2 (aiPLA2), of lysosomal origin, has additionally
      antioxidant properties, (peroxiredoxin VI activity), and participates in the
      formation of dipalmitoyl-phosphatidylcholine in lung surfactant. PAF-AH degrades
      PAF, a potent mediator of inflammation, and oxidatively fragmented phospholipids
      but also leads to toxic metabolites. Therefore, the regulation of PLA2 isoforms
      could be a valuable approach for ARDS treatment.

PMID- 19577641
TI  - Transduced human PEP-1-catalase fusion protein attenuates ischemic neuronal
      damage.
AB  - Antioxidant enzymes are considered to have beneficial effects against various
      diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by
      both oxidative stress and changes in the antioxidant defense system. Catalase
      (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells
      counteract the deleterious effects of ROS. To investigate the protective effects
      of CAT, we constructed PEP-1-CAT cell-permeative expression vectors. When PEP-1
      CAT fusion proteins were added to the culture medium of neuronal cells, they
      rapidly entered the cells and protected them against oxidative stress-induced
      neuronal cell death. Immunohistochemical analysis revealed that PEP-1-CAT
      prevented neuronal cell death in the hippocampus induced by transient forebrain
      ischemia. Moreover, we showed that the protective effect of PEP-1-CAT was
      observed in neuronal cells treated with PEP-1-SOD. Therefore, we suggest that
      transduced PEP-1-CAT and PEP-1-SOD fusion proteins could be useful as therapeutic
      agents for various human diseases related to oxidative stress, including stroke.

PMID- 19577643
TI  - Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective
      delivery system for paclitaxel.
AB  - Paclitaxel (PTX) is an effective anti-cancer drug currently used to treat a wide
      variety of cancers. Unfortunately, nonaqueous vehicle containing Cremophor EL is
      associated with serious clinical side effects. This work aimed to evaluate the
      ability of polymeric micelles to (i) solubilize PTX without Cremophor EL and to
      be used as a (ii) safe and (iii) effective delivery system for PTX. Hence, we
      developed novel self-assembling poly(ethyleneglycol)(750)-block-poly(epsilon
      caprolactone-co-trimethylenecarbonate) (PEG-p-(CL-co-TMC)) polymeric micelles
      which form micelles spontaneously in aqueous solution. The solubility of PTX
      increased up to three orders of magnitude. The PTX-loaded micelles showed a slow
      release of PTX with no burst effect. The HeLa cells viability assessed by the MTT
      test was lower for PTX-loaded micelles than for Taxol (IC(50) 10.6 vs. 17.6
      microg/ml). When solubilized in micelles, PTX induced apoptosis comparable with
      Taxol. The maximum tolerated doses (MTD) of PTX-loaded micelles and Taxol in mice
      were 80 mg/kg and 13.5mg/kg, respectively, after intraperitoneal administration;
      and 45 mg/kg and 13.5mg/kg, respectively, after intravenous administration.
      Similar anti-tumor efficacy of PTX-loaded micelles and Taxol was observed at the
      dose of 13.5mg/kg on TLT-tumor-bearing mice, while the body weight loss was only
      observed in Taxol group. However, as higher dose was tolerated (80 mg/kg - IP), a
      higher growth delay was induced with PTX-loaded micelles. These results
      demonstrated that PTX-loaded self-assembling micelles present a similar anti
      tumor efficacy as Taxol, but significantly reduced the toxicity allowing the
      increase in the dose for better therapeutic response.

PMID- 19577644
TI  - Classification of lyophilised mixtures using multivariate analysis of NIR
      spectra.
AB  - Excipient selection is critically affecting the processing and the stability of a
      lyophilised product. Near infra-red (NIR) spectroscopy was applied to investigate
      freeze-dried samples containing varying ratios of the commonly used excipients
      mannitol and sucrose. Further variation in the formulation was achieved by adding
      NaCl, CaCl(2) and histidine and by exposing the samples to different conditions.
      Untreated NIR spectra are strongly affected by the physical nature of samples and
      can thus be useful for detecting production outliers. Applying standard normal
      variate (SNV) transformation highlights chemical information. The obtained NIR
      spectra of the freeze-dried samples were clustered by principal component
      analysis (PCA) after applying SNV correction in the range from 4200 to 7400cm(-1)
      (1350-2380nm). Relative humidity under storage and the mannitol/sucrose ratio
      were clearly represented in the first two principal components, while influence
      of other excipients was observed in the 3rd and 4th principal component. It was
      investigated whether this could be due to an influence of the excipients on the
      mannitol crystallisation behavior. Performing PCA with two principal components
      of SNV-corrected spectra in the range 4200-4500cm(-1) (2220-1380nm) led to the
      following observation: while the 1st principal component closely resembled the
      spectra of beta-mannitol, the 2nd principal component contained additional
      features that were not attributable to beta-mannitol but correlated well to the
      main absorbance band of delta-mannitol and mannitol hemihydrate. Therefore, it
      seems feasible that NIR can analyse versatile freeze-dried samples and classify
      these according to composition, water content and solid-state properties.

PMID- 19577646
TI  - Muscle relaxant and neurotoxic activities of intrathecal baclofen in rats.
AB  - Intrathecal baclofen therapy by the continuous intrathecal infusion of baclofen
      has been shown to be an effective treatment for spasticity in patients with
      spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis
      and other disorders. To demonstrate the efficacy and safety of intrathecal
      baclofen therapy, we investigated the muscle relaxant and neurotoxic activities
      of intrathecal baclofen in rats, compared with intravenous baclofen. Intrathecal
      and intravenous administration of baclofen dose-dependently inhibited the anemic
      decerebrate rigidity with ED(50) values of 0.31microg/animal (=1.1-1.3microg/kg)
      and 0.43mg/kg, respectively. Intrathecal administration of baclofen induced no
      noticeable changes in a spontaneous electroencephalogram at 30microg/animal.
      Intravenous administration of baclofen induced an abnormal electroencephalogram
      with flat waves in all the animals and the no-observed-effect level was estimated
      to be 5mg/kg. In some animals, intravenous administration of baclofen induced
      sporadic spikes or sharp waves with background flat waves, indicating inhibitory
      and excitatory effects on the central nervous system. In conclusion, intrathecal
      administration of baclofen dose-dependently inhibited anemic decerebrate rigidity
      in rats and the effective dose was more than 300 times lower than that of
      intravenous baclofen. The safety margin of intrathecal baclofen was greater than
      that of intravenous baclofen (> or =97 versus 12). These results suggest that
      intrathecal baclofen therapy is superior to systemic baclofen therapy in both
      efficacy and safety.

PMID- 19577645
TI  - Site controlled transgenic mice validating increased expression from human matrix
      metalloproteinase (MMP-1) promoter due to a naturally occurring SNP.
AB  - Matrix metalloproteinases (MMPs) comprise a family of more than 20 members, each
      with the ability to degrade components of the extracellular matrix. The
      interstitial collagenases have the unique capacity to degrade the stromal
      collagens, types I, II and III, the body's most abundant proteins. These
      collagenases include MMP-1, MMP-8, MMP-13 and MMP-14. MMP-1, with a very broad
      expression pattern, has major roles in mediating matrix destruction in many
      diseases. We have described a single nucleotide polymorphism (SNP) in the MMP-1
      promoter that augments transcription. This SNP is the presence or absence of an
      extra guanine (G) at -1607 bp, which creates the sequence 5'-GGAA-3'(2G allele),
      and which is an ETS binding site. Compared to the 1G allele (5'-GAA-3'), the 2G
      SNP is associated with enhanced transcription of MMP-1 and increased enzymatic
      activity. Although murine systems are often used to model human diseases, mice
      have only distant homologues of human MMP-1. Therefore, we used a technique for
      the targeted insertion of a single copy of a gene at the HPRT locus to compare
      expression of the 1G and 2G alleles. We generated transgenic mice with -4372 bp
      of the human MMP-1 promoter containing either the 1G or 2G SNP in front of the
      lac Z (E.coli ss-galactosidase) gene. We measured the relative expression of the
      transgenes in vitro in embryonic stem (ES) cells and in fibroblasts derived from
      embryonic mice. Our data show modest constitutive expression of ss-galactosidase
      mRNA and protein from these alleles, with the 2G allele more transcriptionally
      active than the 1G allele. We conclude that these mice represent a model for
      integration of a single copy of the human MMP-1 promoter into the murine genome,
      and could be used to study MMP-1 gene expression in a murine system.

PMID- 19577649
TI  - Optimization of in vivo high-resolution DTI of non-human primates on a 3T human
      scanner.
AB  - Magnetic resonance (MR) diffusion tensor imaging (DTI) has emerged as a unique
      technique to reveal small anatomical structures of brain by characterizing the
      diffusion process of water molecules within an image voxel. Combined with fiber
      tractography techniques, DTI can be further used to reveal white matter fibers
      and connectivity in the brain non-invasively. The non-human primate brain study
      provides important supplemental means for human brain exploration since the two
      species share close anatomical and functional similarities. There is therefore
      increasing interest in in vivo non-human primate DTI studies. However, several
      technical challenges need to be addressed to perform non-human primate brain DTI
      and fiber tractography. We have established an imaging protocol together with a
      post-acquisition procedure for high-resolution in vivo non-human primate DTI
      studies using a 3T human clinical scanner. Data acquired with this procedure is
      appropriate for accurate diffusion tensor quantification and fiber tractography,
      and is accessible within an acceptable scan time. We investigated in detail the
      effects of spatial resolution and SNR on diffusion tensor-derived quantities and
      fiber tractography. Our results should be of general utility for implementation
      of in vivo non-human primate DTI studies.

PMID- 19577648
TI  - Methods of MRI-based structural imaging in the aging monkey.
AB  - Rhesus monkeys, whose typical lifespan can be as long as 30 years in the presence
      of veterinary care, undergo a cognitive decline as a function of age. While
      cortical neurons are largely preserved in the cerebral cortex, including primary
      motor and visual cortex as well as prefrontal association cortex there is marked
      breakdown of axonal myelin and an overall reduction in white matter predominantly
      in the frontal and temporal lobes. Whether the myelin breakdown is diffuse or
      specific to individual white matter fiber pathways is important to be known with
      certainty. To this end the delineation and quantification of specific
      frontotemporal fiber pathways within the frontal and temporal lobes is essential
      to determine which structures are altered and the extent to which these
      alterations correlate with behavioral findings. The capability of studying the
      living brain non-invasively with MRI opens up a new window in structural
      functional and anatomic-clinical relationships allowing the integration of
      information derived from different scanning modalities in the same subject. For
      instance, for any particular voxel in the cerebrum we can obtain structural T1-,
      diffusion- and magnetization transfer- magnetic resonance imaging (MRI) based
      information. Moreover, it is thus possible to follow any observed changes
      longitudinally over time. These acquisitions of multidimensional data in the same
      individual within the same MRI experimental setting would enable the creation of
      a data base of integrated structural MRI-behavioral correlations for normal aging
      monkeys to elucidate the underlying neurobiological mechanisms of functional
      senescence in the aging non-human primate.

PMID- 19577650
TI  - Attentional modulation of stimulus representation in human fronto-parietal
      cortex.
AB  - Evidence from primates suggests that prefrontal and parietal regions selectively
      represent information that is relevant for current behavior. In humans, whilst
      functional imaging has shown that fronto-parietal areas are activated by a range
      of different cognitive demands, the actual content of representation remains
      unclear. The current report describes two studies designed to address this issue
      using fMRI adaptation. In both studies, participants completed a delayed matching
      task where they attended to either the color or the shape of a series of sample
      stimuli and indicated whether occasional test stimuli matched the preceding
      sample on the attended dimension. Whole brain contrasts showed that changes to
      the value of the currently attended dimension produced significantly greater
      responses in frontal and parietal areas than events where the value was repeated.
      In addition, prefrontal and parietal regions of interest showed strong
      interactions between the currently attended dimension and the type of stimulus
      change, reflecting an attentional modulation of responses to stimulus change.
      Further comparisons suggested that the differences between attended changes and
      stimulus repetitions carried information about specific stimulus values, and did
      not simply reflect a generic response to attended changes.

PMID- 19577647
TI  - New insights into the role of brain-derived neurotrophic factor in synaptic
      plasticity.
AB  - Substantial evidence indicates that brain-derived neurotrophic factor (BDNF)
      plays a crucial role in synaptic plasticity. Long-lasting synaptic plasticity is
      restricted to active synapses and requires new protein synthesis. Recent work has
      identified local protein synthesis as an important source for new protein during
      the expression of enduring synaptic plasticity. This review discusses recent
      progress in understanding the mechanisms that restrict the action of BDNF to
      active synapses and by which BDNF mediates chemical and structural modifications
      of individual synapses, placing an emphasis on the role of local protein
      synthesis in these processes.

PMID- 19577652
TI  - Bootstrap quantification of cardiac pulsation artifact in DTI.
AB  - While several studies have shown the benefit of cardiac gating in diffusion MRI
      with single-shot EPI acquisition, cardiac gating is still not commonly used. This
      is probably because it requires additional time and many investigators may not be
      convinced that cardiac gating is worth the extra effort. Here, we tested a
      clinically feasible protocol with a minimal increase in scan time, and quantified
      the effect of cardiac gating under partial or full Fourier acquisition. Eight
      volunteers were scanned on a 3 T scanner with a SENSE 8-channel head coil.
      Diffusion-weighted, single-shot spin-echo EPI images were acquired along 32
      gradient directions, with or without cardiac gating and with partial or full
      Fourier acquisition. Vectorcardiography (VCG) was used to trigger acquisition at
      a minimum delay (30 ms). The uncertainties of DTI derived parameters were
      estimated using residual bootstrap. With partial Fourier, cardiac gating reduced
      the uncertainties, and better efficiency in reducing DTI parameter variability
      was also achieved even allowing for the increase in total scan time. For full
      Fourier acquisition, minimum time gating slightly decreased the uncertainties but
      the efficiency was worse. A minimum trigger delay might not be the optimal scheme
      to avoid the majority of systole but it allows clinically acceptable scan times.
      We have demonstrated that cardiac gating, especially of partial Fourier
      acquisitions, can reduce the uncertainties of DTI derived parameters in a time
      efficient manner.

PMID- 19577653
TI  - A mitogenomic perspective on the phylogeny and biogeography of living caecilians
      (Amphibia: Gymnophiona).
AB  - The caecilians, members of the amphibian Order Gymnophiona, are the least known
      Order of tetrapods, and their intra-relationships, especially within its largest
      group, the Family Caeciliidae (57% of all caecilian species), remain
      controversial. We sequenced thirteen complete caecilian mitochondrial genomes,
      including twelve species of caeciliids, using a universal primer set strategy.
      These new sequences, together with eight published caecilian mitochondrial
      genomes, were analyzed by maximum parsimony, partitioned maximum-likelihood and
      partitioned Bayesian approaches at both nucleotide and amino acid levels, to
      study the intra-relationships of caecilians. An additional multiple gene dataset
      including most of the caecilian nucleotide sequences currently available in
      GenBank produced phylogenetic results that are fully compatible with those based
      on the mitogenomic data. Our phylogenetic results are summarized as follow. The
      caecilian family Rhinatrematidae is the sister taxon to all other caecilians.
      Beyond Rhinatrematidae, a clade comprising the Ichthyophlidae and Uraeotyphlidae
      is separated from a clade containing all remaining caecilians (Scolecomorphidae,
      Typhlonectidae and Caeciliidae). Within this large clade, Scolecomorphidae is the
      sister taxon of Typhlonectidae and Caeciliidae but this placement did not receive
      strong support in all analyses. Caeciliidae is paraphyletic with regard to
      Typhlonectidae, and can be divided into three well-supported groups: Caeciliidae
      group 1 contains the African caeciliids Boulengerula and Herpele; Caeciliidae
      group 2 contains Caecilia and Oscaecilia and it is the sister taxon of
      Typhlonectidae; Caeciliidae group 3 comprises the remaining species of
      caeciliids. The mitochondrial genome data were also used to calculate divergence
      times for caecilian evolution using the penalized likelihood method implemented
      in the program R8S. The newly obtained dating results are compatible with (but a
      little older than) previous time estimates mainly based on nuclear gene data. The
      mitogenomic time tree of caecilians suggests that the initial diversification of
      extant caecilians most probably took place in Late Triassic about 228 (195-260)
      Ma. Caeciliids currently distributed in India and the Seychelles diverged from
      their African and American relatives most probably in Late Jurassic about 138
      (112-165) Ma, fairly close to the time (approximately 130Ma) when Madagascar
      India-Seychelles separated from Africa and South America. The split between the
      Indian caeciliid Gegeneophis and Seychellean caeciliids occurred about 103 (78
      125) Ma, predated the rifting of India and the Seychelles (approximately 65Ma).

PMID- 19577654
TI  - Lack of a genetic bottleneck in a recent Lessepsian bioinvader, the blue-barred
      parrotfish, Scarus ghobban.
AB  - The present study investigates the genetic diversity of Scarus ghobban, a
      recently introduced parrotfish in the Mediterranean Sea via the Suez Canal. Two
      mitochondrial and one nuclear DNA regions were sequenced and phylogenetic
      relationships investigated, from samples collected from Lebanon and across its
      natural range. Scarus ghobban clustered in two major clades, Pacific Ocean and
      Indian Ocean, indicating strong population structure, or cryptic speciation.
      Expectedly, Mediterranean samples clustered with Indian Ocean-Red Sea
      individuals. However, unlike other recent Lessepsian invaders, S. ghobban
      displayed high genetic diversity. These results underscore that genetic diversity
      is a poor predictor of success of an invasive species.

PMID- 19577655
TI  - Expanded phylogenies of canonical and non-canonical types of methionine
      adenosyltransferase reveal a complex history of these gene families in
      eukaryotes.
AB  - Most eukaryotes possess the highly-conserved enzyme methionine
      adenosyltransferase (MAT) that produces S-adenosyl-l-methionine, a molecule
      essential to a variety of cellular processes. However, a recent study revealed
      that genomes of a very few eukaryote lineages encode a highly divergent type of
      MAT (called MATX), instead of the canonical MAT enzyme. Since MATX-containing
      eukaryotes are phylogenetically interspersed with MAT-containing organisms, it is
      likely that the MATX gene was spread into the MAT-containing groups via multiple
      eukaryote-to-eukaryote lateral gene transfer events. Here, we further investigate
      the evolutionary history of these gene families by vastly increasing the sampling
      of species containing MAT (22 new taxa) and MATX (8 new taxa). Our expanded
      analyses reveal the first example of lateral transfer of a MAT gene between the
      pelagophycean alga Aureococcusanophagefferens and a cryptomonad. The increased
      MATX sampling also provided new insights into the evolution of MATX.
      Specifically, our MATX phylogeny robustly grouped the haptophyte homologues with
      the Aureococcus homologue to the exclusion of the diatom homologues, suggesting a
      transfer of the MATX gene between haptophytes and pelagophytes. Various scenarios
      of MAT and MATX gene family evolution in diatoms are re-evaluated in light of the
      new data.

PMID- 19577651
TI  - Age-related cognitive gains are mediated by the effects of white matter
      development on brain network integration.
AB  - A fundamental, yet rarely tested premise of developmental cognitive neuroscience
      is that changes in brain activity and improvements in behavioral control across
      adolescent development are related to brain maturational factors that shape a
      more efficient, highly-interconnected brain in adulthood. We present the first
      multimodal neuroimaging study to empirically demonstrate that maturation of
      executive cognitive ability is directly associated with the relationship of white
      matter development and age-related changes in neural network functional
      integration. In this study, we identified specific white matter regions whose
      maturation across adolescence appears to reduce reliance on local processing in
      brain regions recruited for conscious, deliberate cognitive control in favor of a
      more widely distributed profile of functionally-integrated brain activity.
      Greater white matter coherence with age was associated with both increases and
      decreases in functional connectivity within task-engaged functional circuits.
      Importantly, these associations between white matter development and brain system
      functional integration were related to behavioral performance on tests of
      response inhibition, demonstrating their importance in the maturation of optimal
      cognitive control.

PMID- 19577656
TI  - Detection and characterization of circulating endothelial progenitor cells in
      normal rat blood.
AB  - INTRODUCTION: There are currently few widely accepted noninvasive detection
      methods for drug-induced vascular damage. Circulating endothelial progenitor cell
      (EPC) enumeration in humans has recently gained attention as a potential
      biomarker of vascular injury/endothelial damage/dysfunction. The rat is commonly
      used in preclinical drug development toxicity testing and lacks consensus
      noninvasive methodologies for immunophenotypic identification of EPCs.
      Identification of immunophenotypic markers of EPCs in the rat would enable
      transfer of technologies used in human for potential development of biomarkers
      for vascular injury the rat. Therefore, the aim of this work was to develop
      methods to consistently identify a discreet population of EPCs from rat
      peripheral blood. METHODS: EPCs were identified phenotypically from rat blood
      using cell culture, immunolabeling, fluorescence microscopy, and flow cytometry.
      EPCs isolated using immunolabeling coupled with magnetic separation and flow
      cytometric cell sorting were characterized genotypically using mRNA analysis.
      RESULTS: A modified colony forming unit (CFU)-Hill assay confirmed existence of
      immature EPCs in peripheral blood. Extended in vitro culture resulted in a
      morphology and immunophenotype consistent with mature endothelial cells as noted
      by positive staining for CD31, von Willebrand factor, rat endothelial cell
      antigen, and negative staining for smooth muscle cell alpha-actin. The majority
      of the cells identified as LDL+/CD11b/c(-) did not stain positively for either
      vWF or CD31. EPC populations isolated using magnetic separation and cell sorting
      were consistently positive for PECAM1, EDN1, FLK1, VWF, ITGAD, CCR1, IP30, and
      MMP2 mRNA expression. Cells identified as EPCs express cell-surface and gene
      expression markers consistent with endothelial cells and endothelial progenitor
      cell populations. DISCUSSION: Vascular trauma induces transient mobilization of
      EPCs in humans and their enumeration and characterization have been proposed as a
      surrogate biomarker for assessment of vascular injury. Potential exists for using
      rat circulating EPCs as a surrogate sampling population for biomarker development
      in drug-related injury in preclinical toxicity studies. A prerequisite to
      biomarker development is the ability to consistently identify a discreet
      population of EPCs from peripheral rat blood. This work describes novel methods
      for isolation and validation of phenotypically and genotypically consistent
      populations of rat EPCs from peripheral blood. These methods are well suited for
      potential future use in validation of enumeration and/or biomarker development
      methods in the rat.

PMID- 19577657
TI  - The use of X-ray scattering techniques to quantify the orientation and
      distribution of collagen in the corneal stroma.
AB  - The bulk of the corneal stroma is comprised of a layered network of fibrillar
      collagen. Determining the architecture of this unique structure may help us to
      better understand the cornea's biomechanical and optical function. The analysis
      of diffraction patterns obtained when X-rays are passed through the regularly
      arranged collagen molecules and fibrils of the stromal matrix yields quantitative
      data on fibrillar organisation, including the orientation and distribution of
      collagen lamellae within the corneal plane. In recent years, by exploiting the
      radiation from powerful synchrotron sources, techniques have been developed to
      enable the mapping of collagen fibril, and therefore lamellar, directions across
      whole corneas. This article aims to summarise the use of X-ray diffraction to map
      the orientation and distribution of collagen in the corneal stroma. The
      implications of the knowledge gained so far are discussed in relation to the
      optical and biomechanical properties of the cornea, and their alteration due to
      disease and surgical intervention.

PMID- 19577659
TI  - Pam17 and Tim44 act sequentially in protein import into the mitochondrial matrix.
AB  - Import of proteins into the matrix is driven by the Tim23 presequence translocase
      associated import motor PAM. The core component of PAM is the mitochondrial
      chaperone mtHsp70, which ensures efficient translocation of proteins across the
      inner membrane through interactions with the J-protein complex Pam16-Pam18 (Tim16
      Tim14) and its cochaperone Tim44. The recently identified non-essential Pam17 is
      a further member of PAM. Genetic and biochemical analyses reveal synthetic
      interactions between PAM17 and TIM44. Pam17 is involved in an early stage of
      protein translocation whereas Tim44 assists in a later step of transport,
      suggesting that both proteins can cooperate in a complementary manner in protein
      import.

PMID- 19577660
TI  - Apoptosis signaling in cancer stem cells.
AB  - Since the discovery of specific populations of cells with stem-like
      characteristics in human leukemias, phenotypically and/or functionally similar
      tumor-promoting cells have been identified in a variety of human cancers. By dint
      of the similarities to normal human stem cells in terms of self-renewal,
      differentiation, long life span, and proliferative capacity, these defined
      populations of cells within the bulk tumor are referred to as "cancer stem cells
      (CSCs)". The presence of CSCs has challenged the age-old dogma of carcinogenesis,
      which posits that all cells within a tissue retain the capacity to generate
      tumors. With respect to the frequency of CSCs, there is still a lack of consensus
      as in some recent models the notion that these cells constitute a very small
      proportion within the tumor has been challenged. Another issue that remains
      unresolved is the existence of a "global" marker, although reference has been
      made to the CD133(+), CD34(+)CD38(-), and CD44(+)CD24(-) populations as the
      functional stem-like cells in different cancers. Nevertheless, the identification
      of this sub-set within the bulk tumor and its contribution to chemotherapy
      resistance suggest that the CSCs could be the Achilles heel in terms of
      chemosensitization. Therefore, a paradigm is emerging that an effective
      therapeutic approach against cancers is to target this critical pool of cells
      that have the capacity to self-renew and proliferate as well as evade death
      signals. Here we provide a brief review of the literature vis a vis the various
      mechanisms of defective apoptotic signaling in CSCs with potential for
      therapeutic intervention.

PMID- 19577658
TI  - Protein kinase C epsilon is involved in ionizing radiation induced bystander
      response in human cells.
AB  - Our earlier study demonstrated the induction of PKC isoforms (betaII, PKC
      alpha/beta, PKC-theta) by ionizing radiation induced bystander response in human
      cells. In this study, we extended our investigation to yet another important
      member of PKC family, PKC epsilon (PKCepsilon). PKCepsilon functions both as an
      anti-apoptotic and pro-apoptotic protein and it is the only PKC isozyme
      implicated in oncogenesis. Given the importance of PKCepsilon in oncogenesis, we
      wished to determine whether or not PKCepsilon is involved in bystander response.
      Gene expression array analysis demonstrated a 2-3-fold increase in PKCepsilon
      expression in the bystander human primary fibroblast cells that were co-cultured
      in double-sided Mylar dishes for 3h with human primary fibroblast cells
      irradiated with 5Gy of alpha-particles. The elevated PKCepsilon expression in
      bystander cells was verified by quantitative real time PCR. Suppression of
      PKCepsilon expression by small molecule inhibitor Bisindolylmaleimide IX (Ro 31
      8220) considerably reduced the frequency of micronuclei (MN) induced both by 5Gy
      of gamma-rays (low LET) and alpha-particles (high LET) in bystander cells.
      Similar cytoprotective effects were observed in bystander cells after siRNA
      mediated silencing of PKCepsilon suggestive of its critical role in mediating
      some of the bystander effects (BE). Our novel study suggests the possibility that
      PKC signaling pathway may be a critical molecular target for suppression of
      ionizing radiation induced biological effects in bystander cells.

PMID- 19577661
TI  - Anti-HLA I antibodies induce VEGF production by endothelial cells, which
      increases proliferation and paracellular permeability.
AB  - Anti-human leukocyte antigen class I (HLA I) antibodies were shown to activate
      several protein kinases in endothelial cells (ECs), which induces proliferation
      and cell survival. An important phenomenon in antibody-mediated rejection is the
      occurrence of interstitial edema. We investigated the effect of anti-HLA I
      antibodies on endothelial proliferation and permeability, as one possible
      underlying mechanism of edema formation. HLA I antibodies increased the
      permeability of cultured ECs isolated from umbilical veins. Anti-HLA I antibodies
      induced the production of vascular endothelial growth factor (VEGF) by ECs, which
      activated VEGF receptor 2 (VEGFR2) in an autocrine manner. Activated VEGFR2 led
      to a c-Src-dependent phosphorylation of vascular endothelial (VE)-cadherin and
      its degradation. Aberrant VE-cadherin expression resulted in impaired adherens
      junctions, which might lead to increased endothelial permeability. This effect
      was only observed after cross-linking of HLA I molecules by intact antibodies.
      Furthermore, our results suggest that increased endothelial proliferation
      following anti-HLA I treatment occurs via autocrine VEGFR2 activation. Our data
      indicate the ability of anti-HLA I to induce VEGF production in ECs.
      Transactivation of VEGFR2 leads to increased EC proliferation and paracellular
      permeability. The autocrine effect of VEGF on endothelial permeability might be
      an explanation for the formation of interstitial edema after transplantation.

PMID- 19577662
TI  - A pan-PPAR ligand induces hepatic fatty acid oxidation in PPARalpha-/- mice
      possibly through PGC-1 mediated PPARdelta coactivation.
AB  - Tetradecylthioacetic acid (TTA) is a hypolipidemic modified fatty acid and a
      peroxisome proliferator-activated receptor (PPAR) ligand. The mechanisms of TTA
      mediated effects seem to involve the PPARs, but the effects have not been
      assigned to any specific PPAR subtype. PPARalpha-/- mice were employed to study
      the role of PPARalpha after TTA treatment. We also performed in vitro
      transfection assays to obtain mechanistic knowledge of how TTA affected PPAR
      activation in the presence of PPARgamma coactivator (PGC)-1 and steroid receptor
      coactivators (SRC)-1 and SRC-2, which are associated with energy balance and
      mitochondrial biogenesis. We show that TTA increases hepatic fatty acid beta
      oxidation in PPARalpha-/- mice. TTA acts as a pan-PPAR ligand in vitro, and PGC
      1, SRC-1 and SRC-2 have cell type and PPAR-specific effects together with TTA. In
      the absence of exogenous ligands, SRC-1 did not induce PPAR activity, while PGC-1
      was the most potent PPAR coactivator. When the coactivators were overexpressed,
      pronounced effects of TTA were observed especially for PPARdelta and PPARgamma.
      We conclude that PPARalpha is involved in, but not required for, the
      hypolipidemic mechanisms of TTA. It appears that the activity of PPARdelta, with
      substantial contribution of nuclear receptor coactivators, PGC-1 in special, is
      conducive to TTA's mechanism of action.

PMID- 19577663
TI  - Transfection of HGF gene enhances endothelial progenitor cell (EPC) function and
      improves EPC transplant efficiency for balloon-induced arterial injury in
      hypercholesterolemic rats.
AB  - Risk factors for coronary heart disease can reduce the number of endothelial
      progenitor cells (EPCs) and impair EPC function, thus hindering their utility in
      the treatment of cardiovascular diseases. In the present study, we began
      exploring the feasibility of genetic modification of EPCs with hepatocyte growth
      factor (HGF) to counter the effects of these risk factors and enhance the
      biological functions of EPCs. The effects of HGF transfection on proliferation,
      migration and angiogenesis of EPCs were investigated. Additionally, the role of
      ERK1/2 in this process was evaluated through the observation of ERK1/2 and ERK1/2
      phosphorylation as well as by pharmacological analysis. Finally, we evaluated the
      effect of HGF-transfected EPCs (HGF-EPCs) on neointima formation after balloon
      induced arterial injury in hypercholesterolemic rats. Our data showed that EPCs
      transfected with the HGF gene released high levels of soluble HGF protein, which
      were maintained for at least nine days. Transfection with HGF also enhanced the
      proliferative, migratory and angiogenic capabilities of EPCs, and promoted the
      activation of ERK1/2 without affecting its expression. ERK1/2 blockade by the
      chemical inhibitor PD98059 partially inhibited these effects. In
      hypercholesterolemic rats, HGF-EPCs homed to the site of vascular injury at a
      significantly higher rate than did EPCs without the exogenous HGF gene.
      Furthermore, systemically applied HGF-EPCs were more effective in decreasing
      neointima formation and increasing re-endothelialization. These data suggest that
      gene delivery combined with EPC transplant may be a practical and promising
      therapy for the prevention of neointimal formation after vascular injury.

PMID- 19577664
TI  - Expression and localization of clathrin heavy chain in Drosophila melanogaster.
AB  - Clathrin-coated vesicles mediate cellular endocytosis of nutrients and molecules
      that are involved in a variety of biological processes. Basic components of the
      vesicle coat are clathrin heavy chain (Chc) and clathrin light chain molecules.
      In Drosophila melanogaster the chc gene function has been analyzed in a number of
      previous studies mainly using genetic approaches. However, the chc mRNA and
      protein expression patterns have not been studied systematically. We have
      generated an antibody that specifically recognizes Chc and we have analyzed chc
      RNA and protein expression patterns throughout embryonic and larval stages. We
      found that chc mRNA and protein are highly expressed from early stages of
      embryogenesis onwards, consistent with genetic studies predicting a maternal
      contribution of the gene function. During subsequent stages mRNA and protein are
      co-expressed in all embryonic cells; however we found an up-regulation in
      specific tissues including the gut, the salivary glands, tracheal system and the
      epidermis. In addition the central nervous system and the nephrocyte-like garland
      cells show strong Chc expression at late embryogenesis. In larvae Chc is highly
      expressed in garland cells, imaginal discs, fat body, salivary glands and the
      ring gland. Subcellularly, we found Chc protein in a vesicle-like pattern within
      the cytoplasm and at the plasma membrane. Co-labeling studies show that Chc is
      partially in contact with the trans-Golgi network and co-localizes with markers
      for early endocytosis. Together, the antibody may serve as a new tool to study
      the function of Chc in clathrin-dependent cellular processes, such as
      endocytosis.

PMID- 19577665
TI  - Medaka dead end encodes a cytoplasmic protein and identifies embryonic and adult
      germ cells.
AB  - dead end (dnd) was identified in zebrafish as a gene encoding an RNA-binding
      protein essential for primordial germ cell (PGC) development and gametogenesis in
      vertebrates. The adult dnd RNA expression has been restricted to the ovary in
      Xenopus or to the testis in mouse. Its protein product is nuclear in chicken germ
      cells but both cytosolic and nuclear in mouse cell cultures. Here we report the
      cloning and expression pattern of Odnd, the medakafish (Oryzias latipes) dnd
      gene. Sequence comparison, gene structure, linkage analysis and expression
      demonstrate that Odnd encodes the medaka Dnd orthologue. A systematic comparison
      of Dnd proteins from five fishes and tetrapod representatives led to the
      identification of five previously unidentified conserved regions besides the RNA
      recognition motif. The Odnd RNA is maternally supplied and preferentially
      segregated with PGCs. Its adult expression occurs in both sexes and is restricted
      to germ cells. In the testis, Odnd is abundant in spermatogonia and meiotic cells
      but absent in sperm. In the ovary, Odnd RNA persists throughout oogenesis.
      Furthermore, we developed a dual color fluorescent in situ hybridization
      procedure allowing for precise comparisons of expression and distribution
      patterns between two genes in medaka embryos and adult tissues. Importantly, this
      procedure co-localized Odnd and Ovasa in testicular germ cells and PGCs.
      Surprisingly, by cell transfection and embryo RNA injection we show that ODnd is
      cytoplasmic in cell cultures, cleavage embryos and PGCs. Therefore, medaka dnd
      encodes a cytoplasmic protein and identifies embryonic and adult germ cells of
      both sexes.

PMID- 19577666
TI  - The protein-solvent glass transition.
AB  - The protein dynamical transition and its connection with the liquid-glass
      transition (GT) of hydration water and aqueous solvents are reviewed. The protein
      solvation shell exhibits a regular glass transition, characterized by steps in
      the specific heat and the thermal expansion coefficient at the calorimetric glass
      temperature T(G) approximately 170 K. It implies that the time scale of the
      structural alpha-relaxation has reached the experimental time window of 1-100 s.
      The protein dynamical transition, identified from elastic neutron scattering
      experiments by enhanced amplitudes of molecular motions exceeding the vibrational
      level, probes the alpha-process on a shorter time scale. The corresponding liquid
      glass transition occurs at higher temperatures, typically 240 K. The GT is
      generally associated with diverging viscosities, the freezing of long-range
      translational diffusion in the supercooled liquid. Due to mutual hydrogen
      bonding, both, protein- and solvent relaxational degrees of freedom slow down in
      paralleled near the GT. However, the freezing of protein motions, where surface
      coupled rotational and librational degrees of freedom are arrested, is better
      characterized as a rubber-glass transition. In contrast, internal protein modes
      such as the rotation of side chains are not affected. Moreover, ligand binding
      experiments with myoglobin in various glass-forming solvents show, that only
      ligand entry and exit rates depend on the local viscosity near the protein
      surface, but protein-internal ligand migration is not coupled to the solvent. The
      GT leads to structural arrest on a macroscopic scale due to the microscopic cage
      effect on the scale of the intermolecular distance. Mode coupling theory provides
      a theoretical framework to understand the microscopic nature of the GT even in
      complex systems. The role of the alpha- and beta-process in the dynamics of
      protein hydration water is evaluated. The protein-solvent GT is triggered by
      hydrogen bond fluctuations, which give rise to fast beta-processes. High
      frequency neutron scattering spectra indicate increasing hydrogen bond braking
      above T(G).

PMID- 19577667
TI  - Microstructure, elastic properties and deformation mechanisms of horn keratin.
AB  - The structure and mechanical properties of the horns from a desert bighorn sheep,
      Ovis canadensis, were examined. Horns must be strong and durable as they are
      subjected to extreme loading impacts, making them superior structural materials.
      Horns are composed of alpha-keratin, a fibrous, structural protein found in hair,
      nails, claws and hooves. Horns have a lamellar structure (2-5microm in thickness)
      stacked in the radial direction with tubules (approximately 40x100microm in
      diameter) dispersed between the lamellae, extending along the length of the horn
      in the growth direction. Compression and bending tests were conducted in both
      rehydrated and ambient dried conditions. The yield strength and elastic modulus
      are anisotropic and are correlated with the orientation of the tubules.
      Rehydrated samples showed significant loss of strength and modulus. Microscopy of
      fractured samples revealed several toughening mechanisms: delamination and
      ligament bridging in bending and delamination and microbuckling of the lamellae
      in compression.

PMID- 19577668
TI  - Development and characterization of titanium-containing hydroxyapatite for
      medical applications.
AB  - Hydroxyapatite containing levels of titanium (TiHA) of up to 1.6 wt.% has been
      produced via a chemical co-precipitation route. The distribution of Ti was seen
      by transmission electron microscopy/energy-dispersive X-ray analysis to be
      uniform throughout as-prepared nanosized TiHA particles (20 nm x 100 nm). The
      incorporation of Ti into the HA structure was found to influence the ceramic
      microstructure on sintering and the grain size was found to decrease from 0.89
      microm with HA to 0.63 microm with 0.8 wt.% TiHA (0.8 TiHA) and 0.45 microm with
      1.6 wt.% TiHA (1.6 TiHA). Rietveld refinement analysis showed that there was a
      proportional increase in both the a and c axis with incorporation of Ti into the
      HA lattice structure, leading to an increase in the cell volume with the addition
      of Ti. Fourier transform-Raman analysis showed a slight increase in the ratio of
      O-H/P-O peaks on TiHA, in comparison with HA. A bone-like apatite layer was
      formed on the surface of TiHA after immersion in simulated body fluid for 3 days,
      which demonstrated the high in vitro bioactivity of TiHA. In vitro culture with
      primary human osteoblast (HOB) cells revealed that TiHA was able to support the
      growth and proliferation of HOB cells in vitro, with a significantly higher cell
      activity being observed on 0.8 TiHA after 7 days of culture in comparison with
      that on HA. Well-organized actin cytoskeletal protein was developed after 1 day
      of culture, and an increase in cell filopodia (attachment) was observed on TiHA
      sample surfaces. The results indicate that TiHA has great potential for
      biomedical applications.

PMID- 19577669
TI  - A 56-year-old female patient with facio-oculo-acoustico-renal syndrome (FOAR)
      syndrome. Report on the natural history and of a novel mutation.
AB  - The facio-oculo-acoustico-renal syndrome (FOAR) is a rare autosomal recessive
      syndrome characterized by the presence of dysmorphic facial features, ocular
      anomalies, sensorineural hearing loss, and proteinuria. Diaphragmatic hernia,
      exomphalos, absent or abnormal corpus callosum, and myopia, can also be part of
      the syndrome. The disorder is caused by mutations of the LRP2 gene located on
      chromosome 2q23.3-q31.1. We hereby report the case of a 56-year-old female
      patient with typical FOAR features. Molecular study of the LRP2 gene revealed the
      presence of a novel splice-site mutation. In addition to what was reported in
      FOAR syndrome, this patient had a megadolichocolon complicated by a volvulus and
      a late-onset renal failure which necessitated hemodyalisis and renal
      transplantation. Reporting aging patients with genetic syndromes will provide
      information about their special needs and lead to improvements in their follow
      up.

PMID- 19577670
TI  - A new mutation in COG7 extends the spectrum of COG subunit deficiencies.
AB  - We describe a patient homozygous for a novel mutation in COG7, coding for one of
      the subunits of the Conserved Oligomeric Golgi complex, involved in retrograde
      vesicular trafficking. His brother showed a similar clinical syndrome and
      glycosylation defect but no DNA could be obtained from this patient. This
      mutation, c.170-7A > G, activates a cryptic splice acceptor and leads to the
      insertion of 2 amino acids at protein level (p.56-57insAT). The insertion
      disturbs the structure and function of the Conserved Oligomeric Golgi complex. In
      comparison to the previously described patients with a different COG7 mutation,
      intrauterine growth retardation and dysmorphic features were absent and there was
      a longer survival.

PMID- 19577671
TI  - Serum hyaluronic acid as a potential marker with a predictive value for further
      radiographic progression of hand osteoarthritis.
AB  - OBJECTIVE: To compare serum levels of hyaluronic acid (HA) between patients with
      erosive and non-erosive hand osteoarthritis (HOA), and investigate its
      association with morphological changes and radiographic progression over 2 years.
      METHODS: Fifty-five women with erosive and 33 women with non-erosive HOA were
      included in this study. All underwent clinical examination, which included
      assessment of pain, swelling, deformity and deviation of small hand joints and
      completed health assessment questionnaires. Serum levels of HA were measured by
      ELISA. Three-phase bone scintigraphy was performed at baseline. Radiographs of
      both hands were performed at baseline and after 2 years and scored according
      Kallman grading scale. RESULTS: Serum levels of HA were significantly higher in
      patients with erosive than with non-erosive HOA (P<0.01). It correlated
      significantly with the number of hand joints with deviations and deformities. HA
      adjusted for age and disease duration significantly correlated with radiographs
      at baseline and after 2 years in all patients with HOA (r=0.560 and r=0.542,
      P<0.01 for both correlations). Although there was an association between HA and
      radiographic score in erosive disease, after adjustment for confounders it
      remained no longer significant. HA adjusted for confounders correlated
      significantly with the late phase in all patients with HOA (r=0.412, P<0.01) and
      in patients with erosive disease (r=0.320, P<0.05). CONCLUSION: HA is increased
      in patients with erosive HOA and could be proposed as a surrogate marker with a
      predictive value for further radiographic progression of HOA in general. Further
      investigation is necessary to confirm these results.

PMID- 19577672
TI  - Intra- and inter-observer reproducibility of volume measurement of knee cartilage
      segmented from the OAI MR image set using a novel semi-automated segmentation
      method.
AB  - OBJECTIVE: We developed a semi-automated method based on a graph-cuts algorithm
      for segmentation and volumetric measurements of the cartilage from high
      resolution knee magnetic resonance (MR) images from the Osteoarthritis Initiative
      (OAI) database and assessed the intra- and inter-observer reproducibility of
      measurements obtained via this method. DESIGN: MR image sets from 20 subjects of
      varying Kellgren-Lawrence (KL) grades (from 0 to IV) on fixed flexion knee
      radiographs were selected from the baseline double-echo and steady-state (DESS)
      knee MR images in the OAI database (0.B.1 Imaging Data set). Two trained
      radiologists independently performed the segmentation of knee cartilage twice
      using the semi-automated method. The volumes of segmented cartilage were computed
      and compared. The intra- and inter-observer reproducibility were determined by
      means of the coefficient of variation (CV%) of repeated cartilage segmented
      volume measurements. The subjects were also divided into the low- (0, I or II)
      and high-KL (III or IV) groups. The differences in cartilage volume measurements
      and CV% within and between the observers were tested with t tests. RESULTS: The
      mean (+/-SD) intra-observer CV% for the 20 cases was 1.29 (+/-1.05)% for observer
      1 and 1.67 (+/-1.14)% for observer 2, while the mean (+/-SD) inter-observer CV%
      was 1.31 (+/-1.26)% for session 1 and 1.79 (+/-1.72)% for session 2. There was no
      significant difference between the two intra-observer CV%'s (P=0.272) and between
      the two inter-observer CV%'s (P=0.353). The mean intra-observer CV% of the low-KL
      group was significantly smaller than that for the high-KL group for observer 1
      (0.83 vs 1.86%: P=0.025). The segmentation processing times used by the two
      observers were significantly different (observer 1 vs 2): (mean 49+/-12 vs 33+/
      6min) for session 1 and (49+/-8 vs 32+/-8min) for session 2. CONCLUSION: The semi
      automated graph-cuts method allowed us to segment and measure cartilage from high
      resolution 3T MR images of the knee with high intra- and inter-observer
      reproducibility in subjects with varying severity of OA.

PMID- 19577675
TI  - Rectal prolapse: a historical perspective.

PMID- 19577676
TI  - Strengthening research capacity in Africa.

PMID- 19577677
TI  - Where are we now with indigenous health?

PMID- 19577678
TI  - UK falling behind on cancer care.

PMID- 19577679
TI  - G8 Summit 2009: what approach will Italy take to health?

PMID- 19577680
TI  - Venice statement: global health initiatives and health systems.

PMID- 19577681
TI  - End to whaling ban?

PMID- 19577682
TI  - Marlene Kong: one of Australia's few Indigenous doctors. Interview by Priya
      Shetty.

PMID- 19577683
TI  - Crisis in the Swat Valley of Pakistan: need for international action.

PMID- 19577684
TI  - Crisis in the Swat Valley of Pakistan: need for international action.

PMID- 19577685
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577686
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577687
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577688
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577689
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577690
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577691
TI  - Rosuvastatin, C-reactive protein, LDL cholesterol, and the JUPITER trial.

PMID- 19577693
TI  - Buried data and the UK Healthcare Commission's legacy.

PMID- 19577694
TI  - Dietary fibre: refining a definition.

PMID- 19577695
TI  - Indigenous health part 1: determinants and disease patterns.
AB  - The world's almost 400 million Indigenous people have low standards of health.
      This poor health is associated with poverty, malnutrition, overcrowding, poor
      hygiene, environmental contamination, and prevalent infections. Inadequate
      clinical care and health promotion, and poor disease prevention services
      aggravate this situation. Some Indigenous groups, as they move from traditional
      to transitional and modern lifestyles, are rapidly acquiring lifestyle diseases,
      such as obesity, cardiovascular disease, and type 2 diabetes, and physical,
      social, and mental disorders linked to misuse of alcohol and of other drugs.
      Correction of these inequities needs increased awareness, political commitment,
      and recognition rather than governmental denial and neglect of these serious and
      complex problems. Indigenous people should be encouraged, trained, and enabled to
      become increasingly involved in overcoming these challenges.

PMID- 19577696
TI  - Indigenous health part 2: the underlying causes of the health gap.
AB  - In this Review we delve into the underlying causes of health disparities between
      Indigenous and non-Indigenous people and provide an Indigenous perspective to
      understanding these inequalities. We are able to present only a snapshot of the
      many research publications about Indigenous health. Our aim is to provide
      clinicians with a framework to better understand such matters. Applying this
      lens, placed in context for each patient, will promote more culturally
      appropriate ways to interact with, to assess, and to treat Indigenous peoples.
      The topics covered include Indigenous notions of health and identity; mental
      health and addictions; urbanisation and environmental stresses; whole health and
      healing; and reconciliation.

PMID- 19577697
TI  - Neuroleptic malignant syndrome versus malignant disease: idiosyncratic or
      synchronous?

PMID- 19577698
TI  - Professional associations and conflict of interest.

PMID- 19577699
TI  - Addressing spouses' unique needs after cardiac surgery when recovery is
      complicated by heart failure.
AB  - BACKGROUND: Cardiac surgery places extensive stress on spouses who often are more
      worried than the patients themselves. Spouses can experience difficult and
      demanding situations when the partner becomes critically ill. OBJECTIVES: To
      identify, describe, and conceptualize the individual needs of spouses of patients
      with complications of heart failure after cardiac surgery. METHODS: Grounded
      theory using a mix of systematic coding, data analysis, and theoretical sampling
      was performed. Spouses, 10 women and 3 men between 39 and 85 years, were
      interviewed. RESULTS: During analysis, the core category of confirmation was
      identified as describing the individual needs of the spouses. The core category
      theoretically binds together three underlying subcategories: security, rest for
      mind and body, and inner strength. Confirmation facilitated acceptance and
      improvement of mental and physical health among spouses. CONCLUSIONS: By
      identifying spouses' needs for security, rest for mind and body, and inner
      strength, health care professionals can confirm these needs throughout the caring
      process, from the critical care period and throughout rehabilitation at home.
      Interventions to confirm spouses' needs are important because they are vital to
      the patients' recovery.

PMID- 19577700
TI  - Dyadic benefit finding after myocardial infarction: a qualitative investigation.
AB  - OBJECTIVE: The aim of this study was to explore the process of dyadic benefit
      finding after myocardial infarction. METHODS: For the purposes of the study, a
      qualitative methodology using intepretative phenomenologic analysis was used.
      Semistructured interviews were conducted with 11 couples. Patients were
      predominantly male, aged between 50 and 70 years, and partners were aged between
      45 and 64 years. All couples were married. RESULTS: In terms of the patients, the
      following themes emerged: a catalyst for change/wake-up call; change of life
      philosophy; being protected/being invincible; humanistic attitudes. With regard
      to the spouses, the following themes emerged: active search for benefit/failure
      to find benefit and improvement of relationship. CONCLUSION: The study revealed
      no compatibility in the process of benefit finding between patients and spouses.
      Clinical implications for cardiac rehabilitation interventions are discussed.

PMID- 19577701
TI  - Health consequences of partner distress in couples coping with heart failure.
AB  - BACKGROUND: Chronic heart failure (HF) is associated with psychologic distress
      for patients and their spouses. Although research indicates that a patient's
      distress can influence the course of illness, less is known about possible
      effects of a spouse's distress on the patient or of a patient's distress on the
      health of the spouse. METHODS AND RESULTS: Baseline home interviews of 60
      patients with HF (43 men, 17 women) and their spouses included assessments of
      each partner's psychologic distress (Hopkins Symptom Checklist-25) and perceived
      general health (Short Form-36 Questionnaire), as well as severity of patients' HF
      symptoms. We repeated the health and HF-symptom assessments in follow-up
      interviews 6 months later. As hypothesized, the spouse's distress at baseline
      predicted an unfavorable course of patients' HF symptoms and general health over
      the next 6 months, independently of the patient's own baseline distress. There
      were no prospective effects of the patient's distress on the spouse's health,
      however, suggesting that partner distress had asymmetric health consequences for
      patients and spouses. CONCLUSION: The results complement other evidence linking
      marital quality to the course of HF and highlight the importance of looking
      beyond the patient to improve prediction of health outcomes.

PMID- 19577702
TI  - Social support, depression, functional status, and gender differences in older
      adults undergoing first-time coronary artery bypass graft surgery.
AB  - BACKGROUND: Older adults have more difficulty with coronary artery bypass graft
      (CABG) surgery than younger adults, partly because of depression and social
      isolation. During hospitalization, older adult patients undergoing CABG name
      nurses as their primary source of social support. METHODS: A secondary analysis
      was used to investigate the relationships among social support, depression,
      functional status, and postoperative length of stay. Included were 70 patients
      undergoing first-time CABG. Patients had a mean age of 72 years and were
      primarily white (94%) and male (66%). Complete data were collected on 63
      participants. RESULTS: Social support was not related to any other variable.
      Preoperative depression and low functional status persisted postoperatively.
      Female patients had greater depression and poorer functional status than male
      patients both preoperatively and postoperatively. No other gender differences
      were found. CONCLUSION: Depression and functional status are amenable to
      intervention. The outcomes of older adult patients (especially female) undergoing
      CABG might improve if nurses preoperatively assess for and intervene to improve
      depression and functional status.

PMID- 19577703
TI  - Patients' and significant others' health-related quality of life one month after
      coronary artery bypass grafting predicts later health-related quality of life.
AB  - OBJECTIVE: To describe and compare the health-related quality of life (HRQoL) of
      patients (N = 367) and significant others (N = 367) and to identify factors
      associated with HRQoL after coronary artery bypass grafting (CABG). METHODS:
      HRQoL was measured by the 15D in 3 stages: 1, 6, and 12 months after CABG. The
      focus in this study is on HRQoL at the second (6 months) and third (12 months)
      stages of the recovery process. Stepwise linear regression analysis was used to
      identify the associations of independent variables with HRQoL. RESULTS: Patients
      had a lower HRQoL than significant others in both stages after CABG. The HRQoL of
      patients and significant others was explained by their HRQoL 1 month after the
      operation. Other significant explanatory factors among patients were cardiac
      symptoms on physical exertion and other additional diseases. Among significant
      others, chronic diseases were associated with HRQoL. CONCLUSION: The HRQoL of
      patients and significant others differed from each other at both 6 and 12 months
      after CABG. Previous HRQoL affects later HRQoL in both patients and significant
      others.

PMID- 19577704
TI  - Information from health care professionals about sexual function and coexistence
      after myocardial infarction: a Swedish national survey.
AB  - BACKGROUND: After a myocardial infarction (MI), many patients and their partners
      experience problems with marital and sexual life. METHODS: A Swedish national
      survey was carried out to obtain knowledge on the information provided by cardiac
      health care professionals on the subject of sexual function and coexistence after
      an MI. It consisted of a questionnaire that was designed, tested, and sent to 121
      coronary care units. RESULTS: The coronary care unit teams rarely provided oral
      or written information about sexual function and coexistence to patients with MI
      or their partners. The health care professionals lacked competence in these
      areas. CONCLUSION: It is essential that health care professionals are educated on
      and inform the patient with MI about the significance of sexual function and
      coexistence. Further research is required regarding patients' and their partners'
      need for information and support in this area.

PMID- 19577705
TI  - Correlation between the Sedation-Agitation Scale and the Bispectral Index in
      ventilated patients in the intensive care unit.
AB  - BACKGROUND: Oversedation masks neurologic changes and increases
      mortality/morbidity, whereas undersedation risks prolonged stress mobilization
      and patient injury. In situations such as deep sedation/analgesia, the Bispectral
      Index (BIS) has potential use as an adjunct to clinical assessment of sedation to
      help determine depth of sedation. Determining the correlation between clinical
      and BIS measures of sedation will help to determine the correct role of BIS in
      intensive care unit (ICU) practice settings. OBJECTIVE: To evaluate the
      correlation between the clinical assessment of sedation using the Sedation
      Agitation Scale (SAS) and the assessment using BIS in ventilated and sedated ICU
      patients. METHODS: ICU patients requiring mechanical ventilation and sedation
      were monitored using the SAS and BIS. Nurses initiated event markers with BIS at
      the time of SAS assessment but were blinded to BIS scores. RESULTS: Data were
      collected on 40 subjects generating 209 paired readings. Moderate positive
      correlation between BIS and SAS values was shown with a Spearman Rank coefficient
      r value of .502 and an r(2) of .252 (P < .0001). Wide ranges of BIS scores were
      observed, especially in very sedated patients. Strong positive correlation was
      noted between BIS and electromyography with an r value of .749 (P < .0001). Age
      and gender significantly influenced BIS/SAS correlations. CONCLUSION: In
      situations in which the clinical assessment is equivocal, BIS monitoring may have
      an adjunctive role in sedation assessment. BIS values should be interpreted with
      caution, however, because electromyography activity and other factors seem to
      confound BIS scores. More research is necessary to determine the role of BIS
      monitoring in ICU practice.

PMID- 19577706
TI  - Transpulmonary thermodilution and pulse pressure variations in a septic patient
      with heterotopic cardiac transplantation.

PMID- 19577707
TI  - Fever of unknown origin (FUO) due to cyclic neutropenia with relative
      bradycardia.
AB  - Fever of unknown origin (FUO) is the diagnosis associated with a variety of
      infectious, neoplastic, or rheumatic/inflammatory disorders. FUOs are associated
      with fevers of > or = 101 degrees F for > or = 3 weeks that remain undiagnosed
      after intensive in-hospital or ambulatory investigation. Many FUOs caused by
      rheumatic/inflammatory disorders are particularly difficult to diagnose because
      of the lack of specific diagnostic tests for many of these disorders. Several
      causes of obscure rheumatic/inflammatory fevers with a genetic ethnic or
      geographic disposition can be eliminated by history alone. Among the obscure
      rheumatic/inflammatory causes of FUO is cyclic neutropenia. Cyclic neutropenia is
      a rare disorder that may occur with autosomally dominant transmission or
      sporadically. As a cause of FUO, cyclic neutropenia is exceedingly rare. The
      clinical diagnosis of cyclic neutropenia is made by recognizing fever cycle
      periodicity as multiples of 7 days, that is, most commonly at 21 or 28-day
      intervals. The severity of cyclic neutropenia symptoms varies; a severe attack
      may be preceded by 1 or more less-severe attacks. If cyclic neutropenia is
      suspected and attacks occur at 21 or 28-day intervals, then the clinician should
      try to relate leukopenia to symptoms. Patients with cyclic neutropenia may have
      myalgias, fever, pharyngitis, oral ulcers, or bilateral anterior cervical
      adenitis. Fever may be accompanied by a pulse-temperature deficit, that is,
      relative bradycardia, which may provide an additional clue to the diagnosis of
      cyclic neutropenia. The diagnosis of cyclic neutropenia is straightforward if
      leukopenia is present when the patient is symptomatic. With cyclic neutropenia,
      clinicians should keep in mind that neutropenia may precede the patient's
      symptoms by 3 to 5 days and a complete blood cell count should be obtained to
      detect neutropenia 3 to 5 days before episodes and at the onset of symptoms. We
      believe this is the first reported case of FUO caused by cyclic neutropenia with
      relative bradycardia.

PMID- 19577708
TI  - Severe Q fever community-acquired pneumonia (CAP) mimicking Legionnaires'
      disease: Clinical significance of cold agglutinins, anti-smooth muscle antibodies
      and thrombocytosis.
AB  - Atypical community-acquired pneumonia (CAP) may be caused by zoonotic or
      nonpulmonary pathogens. However, atypical pathogens are systemic infectious
      disease accompanied by pneumonia in contrast with typical bacterial pathogens
      with infection limited to the lungs and absent extrapulmonary findings.
      Clinically and radiologically, the atypical CAP pathogens that most closely
      resemble each other are psittacosis, Q fever, and Legionnaires' disease.
      Psittacosis can usually be readily suspected or eliminated on the basis of a
      recent psittacine bird contact history. The 2 atypical pneumonias that most
      closely resemble each other clinically are Q fever and Legionnaires' disease. The
      epidemiology of Q fever is related to livestock, and sporadic cases are related
      to contact to parturient cats. In nonendemic areas, Q fever CAP mimics
      Legionnaires' disease most closely. Both Q fever and Legionella CAP have several
      clinical and laboratory features in common. However, there are subtle but
      important differences that allow the astute clinician to differentiate between
      these 2 disorders on the basis of clinical and nonspecific laboratory findings
      before definitive diagnostic tests results are reported. We report a case of
      severe Q fever CAP mimicking Legionnaires' disease in a young adult normal host.
      Her initial zoonotic contact history was negative, and her clinical presentation
      suggested Legionnaires' disease as the most likely diagnosis. Against the
      diagnosis of Legionnaires' disease was the patient's age and occurrence of the
      disease in spring time. In contrast, Legionnaires' disease is usually an
      infection of older individuals and occurs in late summer/fall. Although the
      patient did not have splenomegaly, a common finding in Q fever CAP, she did have
      mild hepatomegaly. Hepatomegaly is a uncommon in Q fever CAP but is not a feature
      of Legionnaires' disease. In the absence of a positive zoonotic contact history,
      the cardinal findings pointing to the diagnosis of Q fever in this case were
      "multiple round opacities" on chest computed tomography scan and thrombocytosis
      during her hospitalization. Against the diagnosis of Legionnaires' disease was
      the absence of hypophosphatemia and highly elevated ferritin levels. In patients
      with atypical pneumonias in whom the clinical presentation and nonspecific
      laboratory findings suggest Legionnaires' disease, but in addition have findings
      not associated with Legionnaires' (eg, hepatomegaly, thrombocytosis), Q fever
      serology should be ordered. We conclude that Q fever may closely mimic
      Legionnaires' disease. Severe atypical CAP with "multiple round opacities" on
      chest x-ray/computed tomography chest scan with elevated anti-smooth muscle
      antibodies or thrombocytosis should suggest the diagnosis of Q fever and prompt
      specific testing for Q fever. Rarely, Q fever CAP may be associated with elevated
      cold agglutinin titers.

PMID- 19577710
TI  - Feedback mechanism between blood vessels and astrocytes in retinal vascular
      development.
AB  - To meet tissue requirements for oxygen, blood vessels are efficiently distributed
      throughout the body. Multiple interactions between the vasculature and
      surrounding tissues are involved in this process. Retinal vascular development is
      controlled by interactions between ganglion cells, astrocytes, and endothelial
      cells. In particular, reciprocal feedback between endothelial cells and
      astrocytes is crucial for proper vascular patterning. Hypoxia-induced vascular
      endothelial growth factor expression in astrocytes plays a key role in retinal
      vascular growth. Recently, leukemia inhibitory factor secreted from endothelial
      cells was shown to act cooperatively with oxygen as a negative feedback signal.
      This reciprocal feedback mechanism provides a promising target for novel
      antiangiogenic strategies against ocular neovascular diseases and cancers. Here,
      we briefly review what is currently known about the molecular events involved in
      the cellular interactions between ganglion cells, astrocytes, and endothelial
      cells that control retinal vascular patterning.

PMID- 19577709
TI  - Cyclooxygenase-2 inhibition and hypoxia-induced pulmonary hypertension: effects
      on pulmonary vascular remodeling and contractility.
AB  - Pulmonary arterial hypertension (PAH) is a significant disease process
      characterized by elevated pulmonary vascular resistance leading to increased
      right ventricular afterload and ultimately progressing to right ventricular
      dysfunction and often death. Irreversible remodeling of the pulmonary vasculature
      is the hallmark of pulmonary hypertension and frequently leads to progressive
      functional decline in patients with PAH despite treatment with currently
      available therapies. Metabolites of the arachidonic acid cascade play an
      important homeostatic role in the pulmonary vasculature, and dysregulation of
      pathways downstream of arachidonic acid plays a central role in the pathobiology
      of PAH. Cyclooxygenase-2 (COX-2) is up-regulated in pulmonary artery smooth
      muscle cells (PASMC) and inflammatory cells during hypoxia and plays a protective
      role in the lung's response to hypoxia. We recently demonstrated that absence of
      COX-2 was detrimental in a mouse model of hypoxia-induced pulmonary hypertension.
      Exposure of COX-2 null mice to hypoxia resulted in severe pulmonary hypertension
      characterized by enhanced pulmonary vascular remodeling and significant up
      regulation of the endothelin-1 receptor ET(A)R in the lung after hypoxia. Absence
      of COX-2 in vitro led to enhanced contractility of PASMC after exposure to
      hypoxia, which could be attenuated by iloprost, a prostaglandin I(2) analog.
      These findings suggest that selective inhibition of COX-2 may have detrimental
      pulmonary vascular consequences in patients with preexisting pulmonary
      hypertension or underlying hypoxemic lung diseases. Here, we discuss our recent
      data demonstrating the adverse consequences of COX-2 inhibition on pulmonary
      vascular remodeling and PASMC contractility.

PMID- 19577711
TI  - The Carney complex gene PRKAR1A plays an essential role in cardiac development
      and myxomagenesis.
AB  - Cardiac myxomas are the most common primary tumors of the heart, although little
      is known about their etiology. Mutations of the protein kinase A regulatory
      subunit gene PRKAR1A cause inherited myxomas in the setting of the Carney complex
      tumor syndrome, providing a possible window for understanding their pathogenesis.
      We recently reported that cardiac-specific knockout of this gene causes
      myxomatous changes in the heart, although the mice die during gestation from
      cardiac failure. In this review, we discuss these findings and place them in the
      larger understanding of how protein kinase A dysregulation might affect cardiac
      function and cause myxomagenesis.

PMID- 19577712
TI  - Cardiac consequences to skeletal muscle-centric therapeutics for Duchenne
      muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal disease of muscle deterioration.
      Duchenne muscular dystrophy affects all striated muscles in the body, including
      the heart. Recent advances in palliative care, largely directed at improving
      respiratory function, have extended life but paradoxically further unmasked
      emergent heart disease in DMD patients. New experimental strategies have shown
      promise in restoring dystrophin in the skeletal muscles of dystrophin- deficient
      animals. These strategies often have little or no capacity for restitution of
      dystrophin in the hearts of these animals. This article draws on both clinical
      data and recent experimental data to posit that effective skeletal muscle
      restricted therapies for DMD will paradoxically heighten cardiomyopathy and heart
      failure in these patients.

PMID- 19577713
TI  - Prokineticin receptors in cardiovascular function: foe or friend?
AB  - Prokineticins are small secreted bioactive peptides, comprising two classes:
      prokineticin-1 and prokineticin-2. They exert their biological activity by
      binding to two G-protein-coupled receptors: prokineticin receptor (PKR) 1 and 2.
      Recent data have demonstrated that PKR1 induces postnatal neovasculogenesis by
      activating adult epicardial-derived progenitor cell differentiation, whereas
      myocardial PRK2 signaling confers detrimental actions on cardiomyocytes, leading
      to dilated cardiomyopathy and release of an unknown paracrine factor to induce
      capillary fenestration and vascular leakage. The knowledge gained from these
      studies leads to a model in which PKR1 and PKR2 signaling exert opposing actions
      in heart physiology and pathophysiology and facilitate the discovery of specific
      agonists and antagonists targeting PKR1 and PKR2 for possible use in treatment of
      cardiovascular diseases.

PMID- 19577715
TI  - Bioethics and the foot and ankle surgeon.

PMID- 19577716
TI  - Correction of metatarsus primus varus with an opening wedge plate: a review of 18
      procedures.
AB  - The opening base wedge osteotomy is a safe and useful surgical alternative for
      correction of moderate to severe hallux valgus deformities with substantial
      metatarsus primus varus. The authors combine the modified McBride bunionectomy
      with a proximal first metatarsal opening base wedge osteotomy. Osteotomy
      stabilization was achieved without bone grafting with a titanium fixation plate
      specifically designed for opening proximal osteotomies. To assess outcomes
      achieved by the use of this fixation device, we reviewed the records of 18
      procedures (16 patients). Preoperative and postoperative weight-bearing
      radiographs were measured to compare changes in the following radiographic
      variables: intermetatarsal angle 1-2, hallux valgus angle, the first metatarsal
      protrusion distance, and the Seiberg Index. The mean follow-up duration was 11
      months (range, 6-17 months). The median intermetatarsal angle decreased by 9
      degrees (range, 2 degrees-15 degrees), the hallux valgus angle decreased by 13.5
      degrees (range, 0 degrees-56 degrees), and the change in first metatarsal
      protrusion distance was +2.6 mm (range, -0.8 to 6.6 mm), and all of these changes
      were statistically significant (P < or = .001). The preoperative to postoperative
      change in the Seiberg Index was not statistically significant (P = .17). In
      regard to the American Orthopaedic Foot and Ankle Society Hallux
      Metatarsophalangeal-Interphalangeal score, the postoperative scores were
      statistically significantly higher than the preoperative scores (P < .001).
      Complications included 2 (11.11%) recurrences, and 1 (5.56%) case of deep vein
      thrombosis. Fourteen patients (16/18 feet, 88.89%) reported satisfaction with the
      surgical results. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577717
TI  - Determining the strongest orientation for "Lisfranc's screw" in transverse plane
      tarsometatarsal injuries: a cadaveric study.
AB  - The treatment of tarsometatarsal joint fracture-dislocations generally consists
      of realignment followed by stabilization with rigid internal fixation. The
      purpose of this study was to determine the strongest orientation for the
      "Lisfranc's screw" for repair of disruption of the articulation between the first
      and second metatarsals and the medial and intermediate cuneiforms. To this end,
      Lisfranc's ligament was sectioned in 6 pairs of fresh-frozen, human cadaver feet,
      after which a 3.5-mm partially threaded, cannulated screw was placed across the
      Lisfranc joint in 1 of 2 opposing directions. In one group, the screw was
      oriented in the more traditional medial cuneiform to second metatarsal base
      direction. In the other group, the screw was oriented from the second metatarsal
      base to the medial cuneiform. After fixation, each construct was pulled to
      transverse plane failure at the tarsometatarsal joint with a servohydraulic
      mechanical testing system. The overall force to failure was 157.04 +/- 54.79 N
      (range, 96.8-249.2 N). For the traditional medial cuneiform to second metatarsal
      base screw orientation group, the mean force to failure was 148.97 +/- 54.93 N,
      whereas for the second metatarsal base to medial cuneiform group the mean force
      to failure was 165.12 +/- 58.57 N, and this difference was not statistically
      significant (P = .2475). Although not statistically significantly different in
      regard to force to failure strength, the authors describe an alternative approach
      to the orientation of "Lisfranc's screw" for stabilization of the relationship of
      the medial cuneiform to the second metatarsal. LEVEL OF CLINICAL EVIDENCE: 5.

PMID- 19577714
TI  - Sulfonylurea receptor 1 subunits of ATP-sensitive potassium channels and
      myocardial ischemia/reperfusion injury.
AB  - K(ATP) channels are generally cardioprotective under conditions of metabolic
      impairment, consisting of pore-forming (Kir6.1 and/or Kir6.2) and sulphonylurea
      binding, modulatory subunits [sulfonylurea receptor (SUR) 1, 2A, or 2B].
      Cardiovascular K(ATP) channels are generally thought to consist of Kir6.2/SUR2A
      subunits (in the case of heart muscle) or Kir6.1/SUR2B subunits (smooth muscle),
      whereas SUR1-containing channels have well-documented roles in pancreatic insulin
      release. Recent data, however, demonstrated the presence of SUR1 subunits in
      mouse cardiac tissue (particularly in atria) and a surprising protection from
      myocardial ischemia/reperfusion in SUR1-null mice. Here, we review some of the
      extra-pancreatic roles assigned to SUR1 subunits and consider whether these might
      be involved in the sequelae of ischemia/reperfusion.

PMID- 19577718
TI  - Thermal properties of first metatarsal osteotomies.
AB  - Heat is generated whenever osteotomies are created, Kirschner wires are inserted,
      holes are drilled, and when bone is reduced with a burr. Although previous
      investigators have determined the combination of time and temperature necessary
      to cause bone injury, to our knowledge, no one has yet specifically studied
      whether the heat generated when osteotomies are performed in the foot reaches
      sufficient levels to damage osseous tissue. Toward that end, the authors designed
      an experiment to measure the change in cadaveric first metatarsal temperature,
      and the time associated with the rise and fall of the bone temperature, in
      response to osteotomies performed with and without concomitant saline solution
      irrigation of the saw blade. The study was conducted on matched pairs
      (contralateral limbs) of cadaveric bone, with one side being irrigated with
      normal saline solution and the other side being osteotomized without saline
      solution irrigation. Osteotomies were created dorsally and plantarly at 3 sites
      in the first metatarsal specimens, specifically at the head, mid-diaphysis, and
      base; and a total of 112 osteotomies were included in the analyses. Regardless of
      whether saline solution irrigation was used, none of the bone specimens reached a
      temperature known to be associated with thermal injury during osteotomy. The use
      of saline solution irrigation did, however, provide a reduction in peak bone
      temperature during osteotomy, and the duration of sustained temperature elevation
      was also shortened with the use of irrigation. LEVEL OF CLINICAL EVIDENCE: 5.

PMID- 19577719
TI  - Treatment of acute Achilles tendon rupture: fibrin glue versus fibrin glue
      augmented with the plantaris longus tendon.
AB  - In the surgical repair of Achilles tendon ruptures, suturing is standard,
      although fibrin glue also has been used for repair since the 1980s. Augmentation
      with the plantaris longus tendon is also a popular technique; however, no study
      has yet compared the outcome of augmented versus only glued repair of ruptured
      Achilles tendons. This study compares the long-term results of surgical repair of
      Achilles tendon rupture with fibrin glue versus fibrin glue augmented with the
      plantaris longus tendon. Forty patients who had undergone Achilles tendon repair
      with fibrin glue took part in a follow-up examination after an average of 11.5
      years. The fibrin group consisted of 16 patients and the fibrin glue augmented
      with plantaris longus tendon group consisted of 15 patients. The modified
      Thermann score (adapted from Weber) and results of an isokinetic force
      measurement were the same in both groups, whereas complications in the 2 groups
      also did not differ. We conclude that augmentation with the plantaris longus
      tendon is not necessary when operatively treating acute ruptured Achilles tendons
      with fibrin glue. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 19577720
TI  - Surgical correction of Haglund's triad using complete detachment and reattachment
      of the Achilles tendon.
AB  - Haglund's triad consists of the simultaneous presentation of the following
      clinical entities: Achilles tendinosis, Haglund's deformity, and retrocalcaneal
      bursitis. In this retrospective study, we review outcomes following the surgical
      treatment of Haglund's triad by means of complete detachment and reattachment of
      the Achilles tendon, removal of the retrocalcaneal exostosis, and excision of the
      retrocalcaneal bursa through a medial J-shaped approach. Patients were identified
      via chart review, and sent consent forms and a questionnaire consisting of a
      visual analog scale (VAS), a satisfaction survey, and the Maryland Foot Score.
      Seventeen patients (22 feet) met the inclusion criteria and returned the consent
      and questionnaires. Their mean age was 51.6 +/- 11.6 years, and the mean duration
      of postoperative follow-up was 40.1 +/- 27.0 months. The mean preoperative VAS
      was 7.9 +/- 2.3, and the postoperative VAS was 1.6 +/- 1.3 (P < .001). The mean
      postoperative Maryland Foot Score was 91.5 +/- 9.1, with 16 good to excellent
      results. Of the 17 patients, 16 were satisfied and only 1 was somewhat
      unsatisfied. Four complications were observed, and 1 of these required further
      surgical intervention. The outcome of this study demonstrated that surgical
      correction of Haglund's triad using a medial "J" approach, complete detachment
      and reattachment of the Achilles tendon, exostectomy, and retrocalcaneal
      bursectomy provided patient satisfaction with limited complications. LEVEL OF
      CLINICAL EVIDENCE: 4.

PMID- 19577721
TI  - A report of two cases of tuberculous arthritis of the ankle.
AB  - Tuberculosis (TB) is a major global health problem, and musculoskeletal TB occurs
      in approximately 10% of extrapulmonary cases. In this article we describe 2 cases
      of ankle joint tuberculous arthritis. Both of the patients were immunocompromised
      and presented with chronic pain and swelling. Both patients described a history
      of antecedent ankle trauma. The clinical presentations were consistent with
      chronic septic arthritis and were nonspecific as to a particular etiology. The
      pathology and microbiology results revealed infection with Mycobacterium
      tuberculosis. Tuberculous infection of bone and joint must be considered when
      predisposing epidemiological factors are present to avoid delay in therapy.
      Further exploration into the relationship of trauma to tuberculosis recrudescence
      is warranted. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577722
TI  - Closed rupture of the tibialis anterior tendon: a report of 2 cases.
AB  - Closed rupture of the tibialis anterior tendon is a rare injury, and it usually
      affects individuals older than 50 years of age. This rare injury tends to occur
      spontaneously, and this often delays diagnosis and adequate treatment. Although
      direct surgical repair of the ruptured tibialis anterior tendon is generally
      considered the treatment of choice, nonanatomic repair, tendon lengthening, or
      tendon transfer might be necessary in cases where shortening of the muscle-tendon
      unit has taken place. In this report, we describe 2 cases that involved the
      surgical repair of closed ruptures of the tibialis anterior tendon. In the first
      case, direct repair was undertaken at approximately 6 months after the onset of
      symptoms, and in the second case repair of the tibialis anterior tendon required
      augmentation tenodesis with the extensor retinaculum. LEVEL OF CLINICAL EVIDENCE:
      4.

PMID- 19577723
TI  - Acute isolated dorsal midtarsal (Chopart's) dislocation: a case report.
AB  - Isolated midtarsal (Chopart's) joint dislocations are rare, although cases
      involving medial, lateral, plantar, and dorsal displacement have been reported.
      These dislocations are often associated with osteochondral fractures. To the best
      of our knowledge, isolated dorsal midtarsal dislocation owing to plantarflexion
      of the forefoot on the hindfoot with the ankle in a neutral or dorsiflexed
      position is rare. In this article, we describe a case of isolated Chopart's
      dorsal dislocation and discuss the mechanism of injury, management, and outcome.
      The patient was treated with open reduction and repair of ligamentous structures,
      and Kirschner wire transfixation. At approximately 96 weeks following treatment,
      the patient was walking without aid, despite the development of posttraumatic
      degenerative changes at the calcaneocuboid joint. In retrospect, primary
      arthrodesis of the calcaneocuboid joint may have been more beneficial for the
      patient. We also describe the unusual mechanism whereby a plantarflexory force
      applied to the forefoot, without ankle plantarflexion, results in dorsal
      dislocation of the midtarsal joint. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577724
TI  - Compression peroneal nerve palsy causing isolated extensor hallucis longus
      dysfunction.
AB  - The authors describe a case of compression-induced peroneal nerve palsy with
      isolated extensor hallucis longus dysfunction that resulted in hallux lag without
      gross drop foot deformity. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577725
TI  - Use of a posterior antiglide plate in a pediatric ankle fracture: a case report.
AB  - The authors describe the case of a 13-year-old male with a Salter-Harris II
      fracture-subluxation of the fibula. Open reduction and internal fixation with a
      posterior antiglide plate achieved mortise stability and avoided penetration of
      the fibular physis by fixation devices. After searching the Medline, EMBASE,
      CINAHL, and the Cochrane Library databases, to our knowledge, there have been no
      published reports describing the advantages associated with the use of a
      posterior antiglide plate for fixation of the immature fibula.

PMID- 19577726
TI  - An unusual cause of foot pain in a child: osteochondrosis of the intermediate
      cuneiform.
AB  - Osteochondrosis of the intermediate cuneiform is a rare entity that may cause
      foot pain and limping in children. We report a case of osteochondrosis of the
      intermediate cuneiform in a child who underwent a spontaneous recovery after
      conservative treatment. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577727
TI  - Peripheral nerve sheath tumor of the medial plantar nerve without tarsal tunnel
      syndrome: a case report.
AB  - Peripheral nerve sheath tumors are relatively uncommon soft tissue tumors, and
      the incidence of peripheral nerve sheath tumors localized to the plantar surface
      of the foot, without symptoms of tarsal tunnel syndrome, is even more rare. In
      this report, we present the rare case of a patient with a peripheral nerve sheath
      tumor originating from the medial plantar nerve in the plantar vault. The tumor
      was enucleated and fully excised under microscopic inspection using fine-tipped
      instrumentation, without en bloc resection of the associated nerve trunk.
      Surgeons should consider peripheral nerve sheath tumor as a cause of plantar foot
      pain, despite the rarity of this disorder. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577728
TI  - First metatarsal head osteoarticular transfer system for salvage of a failed
      hemicap-implant: a case report.
AB  - Osteochondral defects are frequently seen in patients with hallux limitus.
      Historically, such patients have been treated with cheilectomy, arthroplasty,
      osteotomy, fusion, and other joint destructive procedures. We present a case of a
      54-year-old man who presented with a failed hemicap implant of the first
      metatarsal head. Seven months after his initial implant surgery, the patient was
      still experiencing pain and limited function despite conservative treatment
      efforts. In an effort to salvage the joint, an osteoarticular transfer system
      procedure was undertaken. After removal of the 12-mm hemicap implant, a 15 x 12
      mm osteochondral plug was taken from the ipsilateral femoral condyle and press
      fit into the defect in the first metatarsal head. At 6 weeks postoperatively,
      complete consolidation of the graft was observed radiographically. By 6 months
      postoperatively, the patient was able to walk more than 15 miles per week without
      pain while wearing regular shoes. He was subsequently discharged at 1-year
      postoperatively, at which time he neither described nor demonstrated any signs or
      symptoms related to hallux limitus/rigidus. To our knowledge, this particular
      technique has not been previously reported for lesions of this size in the first
      metatarsal head. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577729
TI  - Gradual digital lengthening with autologous bone graft and external fixation for
      correction of flail toe in a patient with Raynaud's disease.
AB  - Iatrogenic flail toe is a complication of hammertoe surgery that occurs when an
      overaggressive resection of the proximal phalanx occurs. This can cause both
      functional and cosmetic concerns for the patient. We present a case report of the
      correction of a flail second toe in a patient with Raynaud's disease. The
      correction was achieved by means of gradual soft tissue lengthening with external
      fixation and an interposition autologous bone graft digital arthrodesis. After 5
      months, this 2-stage procedure lengthened, stabilized, and restored the function
      of the toe. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577730
TI  - Resection and reconstruction of an osteochondroma of the hallux: a review of
      benign bone tumors and a description of an unusual case.
AB  - Osteochondroma, which is also known as exostosis, is the most common benign bone
      tumor. Although foot and hand surgeons frequently encounter the subungual
      exostosis, exostoses commonly localize to other areas of the skeleton as well. In
      this review, we describe the clinical and diagnostic imaging characteristics of
      benign bone tumors and, in particular, the osteochondroma and its surgical
      management. We also report the case of a patient who experienced an unusual pedal
      digital osteochondroma-like lesion. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19577731
TI  - The Cotton osteotomy: a technical guide.
AB  - The authors in this study hope to offer a summation of the classic and recent
      literature while offering a detailed illustrated technique guide for the medial
      cuneiform, or "Cotton osteotomy." Usually performed as an ancillary procedure,
      the Cotton osteotomy offers the surgeon an additional option for correction of
      various distal medial column deformities while preserving midfoot articular
      surfaces.

PMID- 19577732
TI  - Use of a tibial ACL guide for precision reaming in ankle arthrodesis nailing.
AB  - The correct placement of hindfoot arthrodesis nails can be difficult, especially
      when a nail with valgus banding is used. The authors describe a simple and
      inexpensive technique to facilitate the alignment in tibiotalocalcaneal
      arthrodesis.

PMID- 19577733
TI  - An adaptation of Weil's osteotomy of the lesser metatarsal neck.
AB  - Weil's osteotomy is a useful technique for the treatment of central metatarsalgia
      and lesser metatarsophalangeal joint dislocation. In this report, we describe a
      technical maneuver that involves predrilling and tapping holes that can be used
      to guide translocation of the capital fragment of the metatarsal. This configures
      the final hole that will be used for single screw placement to secure the
      osteotomy in the position of correction. This technical tip is useful in regard
      to establishing the intraoperative orientation of the osteotomy and screw
      placement, and enables the use of a single, generic screw for stabilization of
      the realigned metatarsal.

PMID- 19577734
TI  - Limb salvage versus amputation in the setting of an amended calcaneal bone biopsy
      report.
AB  - Limb salvage is a common and often challenging aspect of lower extremity surgery.
      In some cases, the surgeon's efforts to preserve anatomy and function may
      conflict with patient expectations and lead to situations that require surgeons
      to take into consideration a variety of ethical issues. This can be particularly
      true in a case where an inaccurate diagnosis alters the patient's prognosis.

PMID- 19577735
TI  - The nuclear transport machinery in Caenorhabditis elegans: A central role in
      morphogenesis.
AB  - Our full understanding of the various roles for the nuclear transport machinery
      has come from a variety of model organisms including yeast, nematodes, fruit
      flies and vertebrates. Using the nematode Caenorhabditis elegans, it has been
      shown that the karyopherin family of nuclear transporters and the components of
      the Ran cycle have roles not only in nuclear protein transport, but also in
      mitotic spindle formation and regulation, and in nuclear envelope assembly. These
      studies have also demonstrated a role for nuclear transport factors in cellular
      differentiation and development, particularly for the formation of germ cells.
      This review highlights the small number of studies in C. elegans that have been
      critical to our understanding of this important cellular process.

PMID- 19577737
TI  - The effect of accountability on loss aversion.
AB  - This paper investigates the effect of accountability-the expectation on the side
      of the decision maker of having to justify his/her decisions to somebody else-on
      loss aversion. Loss aversion is commonly thought to be the strongest component of
      risk aversion. Accountability is found to reduce the bias of loss aversion. This
      effect is explained by the higher cognitive effort induced by accountability,
      which triggers a rational check on emotional reactions at the base of loss
      aversion, leading to a reduction of the latter. Connections to dual-processing
      models are discussed.

PMID- 19577738
TI  - Emotional dysregulation in dysphoria: support for Emotion Context Insensitivity
      in response to performance-based feedback.
AB  - The Emotion Context Insensitivity (ECI) hypothesis predicts that individuals
      experiencing a sad mood will show diminished reactivity to emotionally evocative
      stimuli and will not differentiate emotional responses across contexts. Previous
      work has primarily been limited to studying depressed individuals' emotional
      responses to film clips, images, and autobiographical memories. The current study
      builds upon this work by examining emotional reactivity of dysphoric (n=47) and
      non-dysphoric (n=54) individuals to positive and negative feedback about their
      performance on a task they were led to believe measured social intelligence.
      Overall, dysphoric individuals reported higher negative emotion and lower
      positive emotion than non-dysphoric individuals before, during, and after
      feedback. However, consistent with ECI, dysphoric individuals displayed
      attenuated emotional reactivity to negative feedback compared to controls.
      Further, dysphoric individuals' emotional response did not differ to positive and
      negative feedback, whereas the non-dysphoric group appropriately differentiated
      their emotional response across these contexts. Findings support the ECI
      hypothesis and broaden its scope to include emotional reactivity to self-relevant
      performance feedback.

PMID- 19577736
TI  - Nuclear pore proteins and cancer.
AB  - Nucleocytoplasmic trafficking of macromolecules, a highly specific and tightly
      regulated process, occurs exclusively through the nuclear pore complex. This
      immense structure is assembled from approximately 30 proteins, termed
      nucleoporins. Here we discuss the four nucleoporins that have been linked to
      cancers, either through elevated expression in tumors (Nup88) or through
      involvement in chromosomal translocations that encode chimeric fusion proteins
      (Tpr, Nup98, Nup214). In each case we consider the normal function of the
      nucleoporin and its translocation partners, as well as what is known about their
      mechanistic contributions to carcinogenesis, particularly in leukemias. Studies
      of nucleoporin-linked cancers have revealed novel mechanisms of oncogenesis and
      in the future, should continue to expand our understanding of cancer biology.

PMID- 19577739
TI  - Automated measurement of permethylated serum N-glycans by MALDI-linear ion trap
      mass spectrometry.
AB  - The use of N-glycan mass spectrometry for clinical diagnostics requires the
      development of robust high-throughput profiling methods. Still, structural
      assignment of glycans requires additional information such as MS(2) fragmentation
      or exoglycosidase digestions. We present a setting which combines a MALDI
      ionization source with a linear ion trap analyzer. This instrumentation allows
      automated measurement of samples thanks to the crystal positioning system,
      combined with MS(n) sequencing options. 2,5-Dihydroxybenzoic acid, commonly used
      for the analysis of glycans, failed to produce the required reproducibility due
      to its non-homogeneous crystallization properties. In contrast, alpha-cyano-4
      hydroxycinnamic acid provided a homogeneous crystallization pattern and
      reproducibility of the measurements. Using serum N-glycans as a test sample, we
      focused on the automation of data collection by optimizing the instrument
      settings. Glycan structures were confirmed by MS(2) analysis. Although sample
      processing still needs optimization, this method provides a reproducible and high
      throughput approach for measurement of N-glycans using a MALDI-linear ion trap
      instrument.

PMID- 19577740
TI  - [Metastatic intestinal perforation secondary to a primary lung tumour].

PMID- 19577741
TI  - Percutaneous endoscopic suturing: an effective treatment for gastrocutaneous
      fistula.
AB  - BACKGROUND: Development of persistent gastrocutaneous fistula and leakage after
      the removal of a PEG tube is a well-known complication. Various treatments
      including medications to alter gastric pH, prokinetic agents, endoscopic
      clipping/suturing, electric and chemical cauterization, argon plasma coagulation,
      and fibrin sealant, have been used with variable success. Although surgical
      closure is the current treatment of choice, most of the elderly patients are poor
      surgical candidates because of multiple comorbid conditions. OBJECTIVE: We
      describe a method of endoscopic suturing of a gastrocutaneous fistula that is a
      safe and cost-effective alternative to surgical closure. DESIGN: Individual case.
      SETTING: Community hospital. PATIENT: One elderly patient. INTERVENTIONS: By
      using a trocar, we placed multiple, long monofilament sutures from the skin
      around the gastrocutaneous fistula in criss-cross fashion. Gastric ends of these
      sutures were pulled from the stomach with a snare under endoscopic visualization.
      Suture knots were made at the gastric end of the sutures and then were pulled
      back from the cutaneous side. Multiple biopsy specimens were obtained from both
      ends of the fistula to promote granulation tissue. Final knots were made at skin
      level to obliterate the fistula. RESULT: Our procedure resulted in complete
      closure of a large, persistently leaking gastrocutaneous fistula in an elderly
      patient within 7 days. The patient tolerated the optimal rate of enteral
      nutrition without further leakage. LIMITATION: Only 1 patient. CONCLUSION: We
      believe that this method of endoscopic suturing along with de-epithelialization
      of the fistula tract for persistent gastrocutaneous fistula is a safe and cost
      effective alternative to surgical closure.

PMID- 19577742
TI  - EUS-guided transesophageal, transgastric, and transcolonic drainage of intra
      abdominal fluid collections and abscesses.
AB  - BACKGROUND: The therapeutic role of EUS is evolving. We report our experience
      with EUS-guided transesophageal, transgastric, and transcolonic drainage of
      various intra-abdominal fluid collections. OBJECTIVE: To determine the technical
      feasibility and clinical outcomes of EUS-guided drainage. DESIGN: Prospective
      case series. SETTING: Academic tertiary referral center. PATIENTS: Patients
      referred for endoscopic drainage of intra-abdominal fluid collections; pancreatic
      pseudocysts amenable to conventional transgastric or transduodenal drainage were
      excluded. INTERVENTIONS: Single-step EUS-guided drainage of fluid collections by
      using a therapeutic linear-array echoendoscope with fluoroscopic guidance. MAIN
      OUTCOME MEASUREMENTS: Technical success, relief of symptoms, and procedural
      complications. RESULTS: Nine consecutive patients deemed appropriate for EUS
      guided drainage of intra-abdominal fluid collections included transesophageal
      drainage of pseudocysts (n = 2), transgastric drainage of biloma (n = 2) and
      upper intra-abdominal abscesses (n = 2), transcolonic drainage of diverticular
      abscess (n = 1), Crohn's abscess (n = 1), and postoperative hematoma (n = 1).
      Endoscopic drainage was successful in all patients. Confirmation of complete
      resolution of the target fluid collection and symptom relief was achieved in 8
      (89%) of 9 patients. Pneumothorax and mediastinitis developed in 1 patient after
      transesophageal drainage, which resolved with chest tube and medical therapy.
      During multiple stent placement, one of the stents was fully deployed into the
      abscess cavity in 2 patients; both were successfully retrieved either
      endoscopically (Crohn's abscess) or at the time of primary colonic resection
      (diverticular abscess). LIMITATION: Limited number of patients. CONCLUSIONS: EUS
      guided transenteric drainage of bilomas, hematomas, abscesses, and inflammatory
      fluid collections is technically feasible and generally results in complete
      drainage and symptom relief. Procedural complications may be minimized with more
      experience.

PMID- 19577743
TI  - Radiation microsphere-induced GI ulcers after selective internal radiation
      therapy for hepatic tumors: an underrecognized clinical entity.
AB  - BACKGROUND: Intra-arterial infusion of yttrium-90 (Y-90) microspheres is
      locoregional radiation therapy for unresectable hepatic neoplasms. Literature on
      GI complications of this novel therapy is sparse. OBJECTIVES: Clinically and
      pictorially characterize selective internal radiation therapy (SIRT)-induced GI
      injury and review the published literature. DESIGN: Retrospective chart analysis.
      SETTING: Single-center tertiary referral community hospital. PATIENTS: One
      hundred three patients treated with SIRT for hepatic neoplasms between 2006 and
      2008. INTERVENTIONS: SIRT for unresectable hepatic neoplasms followed by upper
      endoscopy with biopsy in symptomatic patients. OUTCOME MEASURES: GI ulcers after
      SIRT. RESULTS: Five patients with suspected GI injury after SIRT were identified.
      Significant postprocedural symptoms included nausea/vomiting, odynophagia,
      hematemesis, and melena. Radiation ulcers occurred mostly in the gastric antrum,
      pylorus, and duodenum. Biopsy specimens of ulcer margins in 4 patients showed
      pathognomonic radiation microspheres. Angiographic review of the fifth patient
      revealed a previously unrecognized arterial branch supplying the corresponding
      region of GI ulceration noted on endoscopy. LIMITATIONS: Small retrospective
      study and follow-up limited by terminal disease states in most patients.
      CONCLUSIONS: The reported incidence of GI complications after SIRT for hepatic
      neoplasia varies from 3% to 24% of patients. Incidence can be minimized by strict
      adherence to published SIRT protocols. Diagnosis requires a high degree of
      clinical suspicion along with endoscopy and biopsy of ulcer margins.
      Characteristic radiation microspheres in biopsy specimens are pathognomonic.
      Gastroenterologists and pathologists must be cognizant of this complication.

PMID- 19577744
TI  - EUS in pediatric patients.
AB  - BACKGROUND: The knowledge of EUS use in children is limited. OBJECTIVE: We
      investigated the indications, feasibility, safety, and clinical utility of EUS in
      the management of pediatric GI, pancreatobiliary, and mediastinal diseases.
      DESIGN: Retrospective study. SETTING: Two tertiary referral university hospitals.
      PATIENTS: Consecutive children age younger than 18 years referred over a 7-year
      period for EUS evaluation. RESULTS: Forty EUS scans were performed in 38 children
      with a mean age of 13.5 years. The indications for pancreatobiliary
      endosonography were pancreatitis (n = 10), solid pancreatic mass (n = 7), cystic
      pancreatic mass (n = 1), cyst in the setting of chronic pancreatitis (n = 1),
      suspected annular pancreas (n = 1), celiac plexus block (n = 1), suspected common
      bile duct stone (n = 1), abdominal pain and atrophic pancreas (n = 1), ampullary
      adenoma (n = 1), and abnormal MRCP in a patient with jaundice (n = 1). The
      indications for gastric EUS were mucosal lesions (n = 2) and subepithelial
      lesions (n = 4). The indications for mediastinal endosonography were mediastinal
      masses/lymph nodes (n = 5). The remaining evaluations were performed for
      esophageal stricture (n = 1), unexplained abdominal pain (n = 1), unexplained
      abdominal pain with celiac axis block (n = 1), and perirectal fluid collection (n
      = 1). EUS-guided FNA (EUS-FNA) was performed in 12 (30%) cases and established
      the correct diagnosis in 9 (75%). EUS-guided fine-needle injections for celiac
      axis block were performed in 2 (5%) cases. The procedure was successful in all
      patients, and no complications related to sedation, EUS, or EUS-FNA were
      encountered. LIMITATION: Retrospective study. CONCLUSION: EUS and EUS-FNA are
      feasible and safe and have a significant impact on the management of pediatric
      GI, pancreatobiliary, and mediastinal diseases.

PMID- 19577745
TI  - EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a
      randomized, double-blind study.
AB  - BACKGROUND: Surgery for pancreatic cysts is associated with significant
      morbidity. A pilot study previously demonstrated the safety of EUS-guided ethanol
      lavage of pancreatic cysts. OBJECTIVE: To determine whether EUS-guided ethanol
      lavage would decrease pancreatic cyst size more than saline solution lavage.
      DESIGN: Prospective, multicenter, randomized trial. SETTING: Two tertiary
      referral hospitals in the United States. PATIENTS: Patients referred for EUS with
      a 1- to 5-cm unilocular pancreatic cyst were randomized to blinded ethanol or
      saline solution lavage. Three months later, the cyst diameter was remeasured by
      EUS, and a second unblinded ethanol lavage was performed. INTERVENTIONS: EUS
      guided pancreatic cyst lavage. MAIN OUTCOME MEASUREMENTS: Cyst ablation based on
      size changes from follow-up EUS, CT, and histology of resected specimens.
      RESULTS: Of 58 patients randomized, 16 were excluded and 42 underwent initial
      ethanol (n = 25) or saline solution (n = 17) lavage. Ethanol lavage resulted in a
      greater mean percentage of decrease in cyst surface area (-42.9; 95% CI, -58.4 to
      -27.4) compared with saline solution alone (-11.4; 95% CI, -25.0 to 2.2; P =
      .009). Nineteen (76.0%) of 25 and 14 (82.3%) of 17 patients randomized to ethanol
      and saline solution, respectively, underwent a second ethanol lavage. A follow-up
      CT scan demonstrated resolution in 12 (33.3%) of 36 cysts. Histology of 4
      resected cysts demonstrated epithelial ablation ranging from 0% (saline solution
      alone) to 50% to 100% (1 or 2 ethanol lavages). Complication rates were similar
      in all groups. LIMITATION: Short-term follow-up. CONCLUSIONS: EUS-guided ethanol
      lavage results in a greater decrease in pancreatic cyst size compared with saline
      solution lavage with a similar safety profile. Overall CT-defined complete
      pancreatic cyst ablation was 33.3%.

PMID- 19577746
TI  - Hymenolepis nana infection of the colon in an adult male.

PMID- 19577747
TI  - Systemic air embolism after ERCP: a case report and review of the literature
      (with video).

PMID- 19577748
TI  - Long-term outcomes of endoscopic submucosal dissection for superficial esophageal
      squamous cell neoplasms.
AB  - BACKGROUND: The long-term outcomes of endoscopic submucosal dissection (ESD) for
      superficial esophageal squamous cell neoplasms (ESCNs) have not been evaluated to
      date. OBJECTIVE: Assess the long-term outcomes of ESD for ESCNs from our
      consecutive cases. DESIGN AND SETTING: Retrospective study from a single
      institution. PATIENTS AND INTERVENTION: From January 2002 to July 2008, 107
      superficial ESCNs in 84 patients were treated by ESD. The enrolled patients were
      divided into 2 groups based on the lesion with the deepest invasion in each
      patient: group A, intraepithelial neoplasm or invasive carcinoma limited to the
      lamina propria mucosa and group B, invasive carcinoma deeper than the lamina
      propria mucosa. MAIN OUTCOME MEASUREMENTS: Rates of en bloc resection, complete
      resection, and complication were evaluated as short-term outcomes. Overall
      survival, cause-specific survival, and postoperative stricture rates were
      evaluated as long-term outcomes. RESULTS: The rates of en bloc resection and
      complete resection were 100% and 88%, respectively. Perforation accompanied by
      mediastinal emphysema was observed in 4 (4%) patients. No patient experienced
      massive bleeding. During the median observation of 632 days (range 8-2358), 15
      (18%) patients experienced benign esophageal stricture with dysphagia, which was
      successfully managed by balloon dilation for a median of 2 sessions (range 1-20).
      One patient had local recurrence 6 months after ESD. In 2 patients with
      intramucosal invasive carcinomas in the muscularis mucosa, distant metastases
      were observed 9 and 18 months after ESD. During the observation period, 3
      patients died of esophageal carcinoma. The 5-year cause-specific survival rates
      of groups A and B were 100% and 85%, respectively. LIMITATIONS: This was a
      retrospective study with a relatively short follow-up and a small number of
      patients from a single institution. CONCLUSION: This long-term follow-up study
      revealed that ESD is a potentially curative treatment for superficial ESCNs.
      There were substantial risks of perforation and stricture that were successfully
      managed endoscopically.

PMID- 19577749
TI  - Lubiprostone neither decreases gastric and small-bowel transit time nor improves
      visualization of small bowel for capsule endoscopy: a double-blind, placebo
      controlled study.
AB  - BACKGROUND: Lubiprostone, a selective activator of type 2 chloride channels, is
      approved for treatment of chronic idiopathic constipation and recently
      constipation-predominant irritable bowel syndrome. It has been suggested that
      lubiprostone has a prokinetic effect. OBJECTIVE: This investigation was designed
      to evaluate lubiprostone as a preparation and propulsive agent for small-bowel
      capsule endoscopy. The PillCam Small Bowel capsule endoscopy system with the
      PillCam SB1 capsule and Rapid 5 software platform were used. DESIGN: The study
      was designed as a double-blind, placebo-controlled trial. PATIENTS: Forty healthy
      adults. MAIN OUTCOME MEASURES: Gastric transit time (GTT), small-bowel transit
      time (SBTT), and adequacy of small-bowel cleansing preparation. INTERVENTIONS:
      The study subjects received 24 mug lubiprostone or placebo 30 minutes before
      PillCam capsule ingestion. METHODS: Capsule endoscopy studies were read by 2
      independent investigators unaware of the study medication received, and
      differences in interpretation were resolved by consensus. Anatomical landmarks
      were identified, and GTT and SBTT were calculated. Overall preparation quality
      assessment of the proximal, mid, and distal small bowel was determined by using a
      4-step scale. The percentage of visualized bowel was determined by review of 10
      minute video segments at 1-hour intervals after the capsule passed through the
      pylorus. RESULTS: In the lubiprostone group (n = 20), 2 subjects did not pass the
      capsule through the pylorus in the 8-hour battery life of the capsule. An
      additional 3 capsules did not pass into the colon. In the placebo group (n = 20),
      all capsules passed into the small bowel, but 1 did not pass into the colon. The
      subjects in whom the capsule did not pass into the small bowel were excluded from
      the small-bowel analysis. In the subjects in whom the capsule did reach the
      colon, the SBTT could not be calculated and they were excluded from SBTT
      analysis. The mean GTT in the lubiprostone group was 126 minutes and 43 minutes
      in the placebo group (P = .0095). The mean SBTT in the lubiprostone group was 188
      minutes and 219 minutes in the placebo group (P = .130). The overall preparation
      assessment of the small bowel was not statistically significant between the 2
      groups in the proximal, mid, or distal small bowel (proximal, P = .119; mid, P =
      .118; distal, P = .121). There was no significant difference in lubiprostone
      compared with placebo in the percentage of visualized small bowel. LIMITATIONS:
      Some capsules did not leave the stomach or reach the cecum. CONCLUSION:
      Lubiprostone produced a significant increase in GTT but did not result in a
      significant decrease in SBTT compared with placebo. The administration of
      lubiprostone before capsule ingestion did not result in improved overall
      preparation of the small bowel for capsule endoscopy or increase the percentage
      of visualized small bowel. (The trial was registered at www.clinicaltrials.gov,
      identifier NCT00746395.).

PMID- 19577750
TI  - Dissatisfaction with traditional birth attendants in rural Tanzania.
AB  - OBJECTIVE: To assess women's satisfaction with traditional birth attendants
      (TBAs) in rural Tanzania. METHOD: A population-representative sample of
      households in Kasulu district was used to collect data on demographics,
      childbirth history, and perception of TBAs and doctors/nurses from women who had
      recently had a child and from their partners. RESULTS: Two-thirds of women who
      gave birth in a health facility reported being very satisfied with the
      experience, compared with 21.2% of women who delivered at home with TBAs. A
      sizeable proportion of women felt that TBAs had poor medical skills (23.1%),
      while only 0.3% of women felt the same about doctors' and nurses' skills. Of
      women who delivered with a TBA, 16.0% reported that TBAs had poor medical skills
      whereas 0.5% stated the same for doctors and nurses. CONCLUSION: Although many
      women delivered at home in this rural study district, women and their partners
      reported higher confidence in doctors and nurses than in TBAs. Policymakers and
      program managers should not assume that women prefer TBAs to trained
      professionals for delivery but should consider system barriers to facility
      delivery in interventions aimed at reducing maternal mortality.

PMID- 19577751
TI  - Development and psychometric evaluation of the Dialysis patient-perceived
      Exercise Benefits and Barriers Scale.
AB  - BACKGROUND: Perceptions of exercise benefits and barriers affect exercise
      behavior. Because of the clinical course and treatment, dialysis patients differ
      from the general population in their perceptions of exercise benefits and
      barriers, especially the latter. At present, no valid instruments for assessing
      perceived exercise benefits and barriers in dialysis patients are available.
      OBJECTIVES: Our goal was to develop and test the psychometric properties of the
      Dialysis patient-perceived Exercise Benefits and Barriers Scale (DPEBBS).
      METHODS: A literature review and two focus groups were conducted to generate the
      initial item pool. An expert panel examined the content validity. Then, 269
      Chinese hemodialysis patients were recruited by convenience sampling. Exploratory
      and confirmatory factor analyses were used to test construct validity. Finally,
      internal consistency and test-retest reliability were assessed. RESULTS: The
      expert panel determined that the content validity index was satisfactory. The
      final 24-item scale consisted of six factors explaining 57% of the total variance
      in the data. Confirmative factor analysis supported the six-factor structure and
      a higher-order model. Cronbach's alpha was 0.87 for the total scale, and 0.84 for
      test-retest reliability. CONCLUSION: The DPEBBS was a valid and reliable
      instrument for evaluating dialysis patients' perceived benefits and barriers to
      exercise. The application value of this scale remains to be investigated by
      increasing the sample size and evaluating patients undergoing different dialysis
      modalities and coming from different regions and cultural backgrounds.

PMID- 19577752
TI  - Person-centred interactions between nurses and patients during medication
      activities in an acute hospital setting: qualitative observation and interview
      study.
AB  - BACKGROUND: There is increasing emphasis on person-centred care within the
      literature and the health care context. It is suggested that a person-centred
      approach to medication activities has the potential to improve patient
      experiences and outcomes. OBJECTIVES: This study set out to examine how nurses
      and patients interact with each other during medication activities in an acute
      care environment with an underlying philosophy of person-centred care. DESIGN: A
      qualitative approach was used comprising naturalistic observation and semi
      structured interviews. SETTING: The study setting was an acute care ward with a
      collaboratively developed philosophy of person-centre care, in an Australian
      metropolitan hospital. PARTICIPANTS: Eleven nurses of varying levels of
      experience were recruited to participate in observations and interviews. Nurses
      were eligible to participate if they were employed on the study ward in a role
      that incorporated direct patient care, including medication activities. A
      stratified sampling technique ensured that nurses with a range of years of
      clinical experience were represented. Patients who were being cared for by
      participating nurses during the observation period were recruited to participate
      unless they met the following exclusion criteria: those less than 18 years of
      age, non-English speaking patients, and those who were unable to give informed
      consent. Twenty-five patients were observed and 16 of those agreed to be
      interviewed. RESULTS: The results of the study generated insights into the nature
      of interactions between nurses and patients where person-centred care is the
      underlying philosophy of care. Three major themes emerged from the findings:
      provision of individualised care, patient participation and contextual barriers
      to providing person-centred care. While the participating nurses valued a person
      centred approach and perceived that they were conducting medication activities in
      a person-centred way, some nurse-patient interactions during medication
      activities were centred on routines rather than individualised patient assessment
      and management. These interactions were based on nurses' perceptions of what was
      important for the patient and did not provide opportunities for patient
      participation. Two main contextual barriers in relation to a person-centred
      approach to medication activities were identified as multidisciplinary
      communication and time constraints. CONCLUSIONS: While some nurse-patient
      interactions during medication activities were consistent with the principles of
      person-centred care, the study results highlighted factors that influence the
      nature of these interactions, and identified opportunities to improve nursing
      practice. To ensure person-centred care is applied to medication activities,
      nurses should undertake ongoing assessment of patients' needs in relation to
      their medications and encourage opportunities for increased patient
      participation.

PMID- 19577753
TI  - Neopterin levels and left ventricular dysfunction in patients with chronic stable
      angina pectoris.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is the strongest predictor
      of survival in patients with chronic stable angina (CSA). Inflammation plays a
      key role in the pathogenesis of atherosclerosis and an enhanced inflammatory
      status has a negative impact on patient outcome. It is not known whether a
      relationship exists between inflammation and LV function in patients with CSA. We
      therefore sought to investigate whether C reactive protein (CRP) and neopterin
      correlate with LV dysfunction in patients with CSA. METHODS: We assessed 181
      patients with CSA who underwent diagnostic coronary angiography in our
      institution. High-sensitivity CRP and neopterin serum concentrations were
      measured immediately before angiography. RESULTS: Baseline neopterin levels - but
      not CRP - showed a significant inverse correlation with LVEF (r=-0.222; p=0.003
      and r=-0.097; p=0.194, respectively). After adjustment for relevant confounders
      which included, among others, the extent and severity of coronary disease,
      neopterin was found to be independently associated with LVEF (B -2.36, CI 95% 
      4.560 to -0.176, p=0.034). Moreover, high neopterin levels were an independent
      predictor of LV dysfunction (LVEF <45%) (OR, 8.52, CI 95% 1.10-65.64; p=0.040).
      Receiver operating characteristic analysis for neopterin showed an area under the
      curve of 0.736 (CI 95% 0.59-0.87, p<0.009) for prediction of LV dysfunction.
      CONCLUSION: Increased serum neopterin concentrations inversely correlate with
      LVEF values and high neopterin levels are a predictor of LV dysfunction in
      patients with CSA, irrespective of the extent and severity of coronary artery
      disease. Neopterin may thus be clinically useful for patient risk stratification.

PMID- 19577754
TI  - Impact of the metabolic syndrome on high-sensitivity C reactive protein levels in
      patients with acute coronary syndrome.
AB  - OBJECTIVE: Underlying predisposition for a heightened inflammatory response is
      postulated as one of the mechanisms for elevated high-sensitivity C reactive
      protein (hs-CRP) levels in patients with acute coronary syndrome (ACS). It is
      unclear whether metabolic syndrome (MetS) may cause a predisposition for
      heightened hs-CRP response in patients with ACS. The aim of this study is to
      investigate the interaction between hs-CRP levels and presence of MetS in
      patients with and without ACS. METHODS: Two hundred and seventy-three consecutive
      patients presenting with a first ACS event and 261 MetS patients without any ACS
      event were included to the study. The study participants were divided into three
      groups as MetS (+) ACS (-) [n=261], MetS (-) ACS (+) [n=110], and MetS (+) ACS
      (+) [n=163]. Median levels of hs-CRP were compared between and within the three
      groups. RESULTS: Hs-CRP levels were lowest in MetS (+) ACS (-) subjects and
      highest in MetS (+) ACS (+) patients. Factors associated with hs-CRP levels were
      troponin elevation, presence of ACS, body mass index (BMI), and presence of MetS
      (R(2)=0.26, p<0.01). Predictors of elevated hs-CRP levels (>0.3mg/dl) were the
      presence of ACS (OR=3.6, 95% CI=1.9-6.5, p<0.01), presence of MetS (OR=2.1, 95%
      CI=1.0-4.0, p=0.02), troponin elevation (OR=5.7, 95% CI=2.8-11.5, p<0.01) and BMI
      (OR=1.1, 95% CI=1.0-1.1, p<0.01). CONCLUSIONS: The presence of MetS had an impact
      on the increase in hs-CRP levels observed with an ACS event in the study
      population. These findings suggested that a heightened baseline inflammatory
      status of MetS may predispose ACS patients to an augmented hs-CRP response.

PMID- 19577755
TI  - Novel separation medium spongy monolith for high throughput analyses.
AB  - Sponge-like material was utilized as novel chromatographic media for high
      throughput analyses. The pore size of the sponge-like material was several dozen
      micrometer, and was named spongy monolith because it consists of continuous
      structured copolymers, which was made of poly(ethylene-co-vinyl acetate), such as
      monolithic materials including silica monoliths and organic polymer monoliths.
      The spongy monolith was packed into a stainless steel column (100 mm x 4.6 mm
      I.D.) and evaluated in liquid chromatography (LC) with an on-line column
      switching LC concentration system. The results indicate that the packed column
      could be used with high flow rates and low back pressure (9.0 mL/min at 0.5 MPa).
      Furthermore, bisphenol A was quantitatively recovered by on-line column-switching
      LC concentration with the spongy monolithic column. Additionally, the adsorption
      capacity and physical strength of the media was enhanced via chemical
      modification of spongy monoliths using glycerol dimethacrylate. The results
      compared with original spongy monolith demonstrated that a higher adsorption
      capacity was achieved on a shorter column, and a stable low back pressure was
      obtained at high throughput elution even with a longer column.

PMID- 19577756
TI  - Programmed temperature vaporizer based method for the sensitive determination of
      trihalomethanes and benzene, toluene, ethylbenzene and xylenes in soils.
AB  - A methodology based on the coupling of a headspace autosampler with a GC and a MS
      detector operating in SIM mode has been developed for the determination of
      volatile organic compounds (THMs and BTEX) in soils. The GC device used is
      equipped with a programmable temperature vaporizer (PTV) packed with Tenax-TA to
      introduce the samples (the injection mode used was solvent vent), and a modular
      accelerated column heater (MACH) to control column temperature. The proposed
      measurement procedure reduces the sample pretreatment step to a minimum. Combined
      use of solvent vent injection mode and mass spectrometry detection allows a
      highly sensitive method to be proposed, with limits of detection of the order of
      ng/kg for all the target compounds. Furthermore, the capillary column used allows
      rapid separations of compounds in less than 4.60 min, affording a very short
      total analysis cycle time of 9 min.

PMID- 19577757
TI  - Does improving mood in depressed patients alter factors that may affect
      cardiovascular disease risk?
AB  - To determine if improvement in mood would ameliorate autonomic dysregulation, HPA
      dysfunction, typical risk factors and C-reactive protein in depressed patients
      with elevated cardiovascular disease risk (CVD), 48 depressed participants with
      elevated cardiovascular risk factors were randomized to a cognitive behavioral
      intervention (CBT) or a waiting list control (WLC) condition. Twenty non
      depressed age and risk-matched controls were also recruited. Traditional risk
      factors (e.g., lipids, blood pressure) and C-reactive protein were assessed pre-
      and post-treatment six months later. Subjects also underwent a
      psychophysiological stress test while cardiovascular physiology was measured.
      Salivary cortisol was measured during the day and during the psychological stress
      test. At post-treatment, the CBT subjects were significantly less depressed than
      WLC subjects. There was no significant difference in change scores on any of the
      traditional risk factors or C-reactive protein, cortisol measures, or
      cardiovascular physiology, except for triglyceride levels and heart rate, which
      were significantly lower in treatment compared to control subjects. The normal
      controls exhibited no change in the variables measured during the same time. A
      significant improvement in mood may have little impact on most traditional or
      atypical risk factors, cortisol or cardiophysiology.

PMID- 19577758
TI  - Effects of half-solid nutrients on gastroesophageal reflux in beagle dogs with or
      without cardioplasty and intrathoracic cardiopexy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has become an important
      modality to provide enteral access for long-term nutritional support.
      Nevertheless, aspiration of liquid nutrients due to vomiting and reflux
      esophagitis caused by gastroesophageal reflux (GER) is a significant problem
      associated with tube feeding by PEG. MATERIALS AND METHODS: First, gastrostomy as
      an access for enteral nutrition and esophagostomy for gastroesophageal pH and
      Bilitec monitoring were performed in eight beagle dogs, in which the influence of
      viscosity of an enteral formula on the degree of GER was investigated using a
      commercially available liquid meal and a nearly isocaloric half-solid diet that
      was prepared by adding a solution mixed with dextrin, pectin, and calcium
      lactate. Second, similar studies were accomplished in seven beagle dogs that
      underwent cardioplasty and intrathoracic cardiopexy (a model of GER disease
      [GERD]). RESULTS: There was no difference in the degree of GER evaluated by
      Bilitec monitoring between liquid and half-solid nutrients in eight normal dogs,
      whereas solidifying nutrients significantly reduced the frequency of reflux
      during the feeding periods (P=0.0180) and post-feeding periods (P=0.0277) in a
      model of GERD. CONCLUSION: The use of half-solid nutrients for enteral feeding
      reduced the frequency of reflux in a dog model of GERD.

PMID- 19577759
TI  - Outcomes of malignant CNS ependymomas: an examination of 2408 cases through the
      Surveillance, Epidemiology, and End Results (SEER) database (1973-2005).
AB  - BACKGROUND: Determine the role of surgery and radiation therapy for patients with
      malignant CNS ependymomas. METHODS: The Surveillance, Epidemiology, and End
      Results (SEER) database (1973-2005) was queried. RESULTS: Overall, a total of
      2408 cases of malignant ependymomas were identified. Of these, 2132 cases (88.5%)
      were identified as WHO grade II ependymomas and 276 cases (11.5%) as WHO grade
      III (anaplastic) ependymomas. The annual incidence of ependymomas was
      approximately 1.97 cases per million in 2005. Overall median survival for all
      patients was 230 mo, with a significant difference between women and men (262 mo
      versus196 mo, respectively) (P=0.004). Median age at diagnosis was 37 y among
      females and 34 y in males. Patients who successfully underwent surgical resection
      had a considerably longer median survival (237 mo versus 215 mo, P<0.001) as well
      as a significantly improved five-year survival (72.4% versus 52.6%, P<0.001).
      Univariate analysis demonstrated that age, gender, ethnicity, primary tumor site,
      WHO grade and surgical resection were significant predictors of improved survival
      for ependymoma patients. Multivariate analysis identified that a WHO grade III
      tumor, male gender, patient age, intracranial tumor locations and failure to
      undergo surgical resection were independent predictors of poorer outcomes.
      Multivariate analysis of partially resection cases revealed that lack of
      radiation was a sign of poor prognosis (HR 1.748, P=0.024). CONCLUSION: Surgical
      extirpation of ependymomas is associated with significantly improved patient
      survival. For partially resected tumors, radiation therapy provides significant
      survival benefit.

PMID- 19577760
TI  - Diurnal expression and function of peptide transporter 1 (PEPT1).
AB  - BACKGROUND: Protein is absorbed primarily as di/tripeptides, which are
      transported into the enterocyte exclusively by H(+)/peptide cotransporter 1
      (PEPT1). Diurnal changes in expression and function of several other mucosal
      transporters occur in rat. Diurnal variations in mRNA, protein, and transport
      function of PEPT1 occur in rat duodenum and jejunum, but not in ileum. METHODS:
      Mucosal levels of mRNA and protein were determined at 9 AM, 3 PM, 9 PM, and 3 AM
      (n=6 each) by real time RT-PCR and Western blotting, respectively, in rats
      maintained in a 12-h light/dark room [light 6 AM to 6 PM]; transporter-mediated
      uptake of dipeptide (Gly-Sar) was also measured by everted sleeve technique.
      RESULTS: mRNA transcripts of PEPT1 and Gly-Sar uptake varied diurnally in
      duodenum and jejunum (peak at 3 PM, P<0.05), but not in ileum; maximal uptake was
      in jejunum. V(max) (nmol/cm/min) was greater at 3 PM and 9 PM compared with 9 AM
      (3 PM versus 9 AM: 104 versus 62 in duodenum, and 185 versus 101 in jejunum;
      P<0.03); K(m) was unchanged across time points or locations. Protein levels
      varied minimally in jejunum and ileum with peaks at 9 PM and 3 AM. CONCLUSION:
      Gene expression and transport function of PEPT1 vary diurnally in duodenum and
      jejunum in temporal association with nocturnal feeding of rats.

PMID- 19577761
TI  - Setting the stage: Surgery patients' expectations for greetings during routine
      office visits.
AB  - BACKGROUND: The need for surgeons to exhibit adequate communication skills is
      paramount to providing exemplary patient care. The manner in which patients are
      greeted by their surgeon sets the stage for the remainder of the clinical
      encounter. This study examined patients' expectations for greetings upon meeting
      a surgeon for the first time. MATERIALS AND METHODS: A convenience sample of 152
      English-speaking patients (> or =21 y of age) attending a university-based
      vascular surgery clinic were recruited to participate in this study. Eligible
      patients were interviewed prior to their consultation using valid and reliable
      questionnaires to obtain data about sociodemographic characteristics and
      expectations for greetings upon meeting a surgeon for the first time. RESULTS:
      Patients' mean age was 61.4 +/- 14.6 approximately half (n = 81;54.3%) were male,
      and most were Caucasian (n = 148; 97.4%). Most (n = 132; 86.8%) patients wanted
      the surgeon to shake their hand, 113 (74.3%) wanted their first name to be used
      when a surgeon greets them, and 86 (56.6%) wanted a surgeon to introduce
      him/herself using his/her last name. Patients also desired for surgeons to be
      attentive/calm and make patient feel like a priority, adjust vocabulary and/or
      explain better, and be friendly, personable, polite, respectful, and/or
      courteous. CONCLUSIONS: Surgeons should shake hands, use patients' first names,
      and introduce themselves using their last names when greeting patients for the
      first time. They should also be pleasant, personable, and make the patient feel
      like a priority. Additionally, surgeons should be cognizant of the way in which
      they present information to patients and verify understanding.

PMID- 19577762
TI  - Suppression of acute and chronic cardiac allograft rejection in mice by
      inhibition of chemokine receptor 5 in combination with cyclosporine A.
AB  - BACKGROUND: Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor
      expressed on activated T cells, is an effective antiviral therapy in patients
      with HIV infection, but its efficacy in modulating inflammation and immunity is
      only just beginning to be investigated. In this study we examined the inhibition
      of CCR5 in combination with the treatment with cyclosporine A in acute and
      chronic rejection in cardiac transplantation. MATERIALS AND METHODS: Eighty fully
      MHC-mismatched murine cardiac allograft models were randomized to four groups.
      Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B
      were given anti-CCR5 mAb alone, animals in group C were administered only CsA,
      and group D were the control group with PBS. Acute and chronic rejection was
      investigated on day 7 and day 45 post-transplant, respectively. RESULTS:
      Allografts treated with anti-CCR5 mAb plus CsA showed significantly prolonged
      survival (44.73 +/- 0.258 d, P < 0.01) compared with PBS-treated group (11.067 +/
      0.707 d). Treatment with anti-CCR5 mAb plus CsA significantly inhibited the
      progression of CAV. CONCLUSIONS: Our findings demonstrated that anti-CCR5 mAb in
      combination with CsA can prolong the survival of allograft and alleviate both
      acute and chronic allograft rejection. Thus, combined administration of anti-CCR5
      mAb and CsA may become a new therapeutic approach for the prevention of cardiac
      graft failure that has not been obviated by conventional immunosuppressive
      agents.

PMID- 19577763
TI  - Transient lower esophageal sphincter relaxation and esophageal motor response.
AB  - BACKGROUND: Gastroesophageal reflux is caused by transient lower esophageal
      sphincter relaxations (TLESRs) in healthy individuals and in most patients with
      gastroesophageal reflux disease (GERD). Refluxate is normally propelled by
      pharyngeally induced swallowing events, but TLESRs may also be accompanied by
      retrograde esophageal motor responses (EMRs). These contractions have not
      previously been investigated and their effect on esophageal clearance is not
      known. The aim of this study was to assess the frequency of EMRs after TLESR in
      healthy individuals and GERD patients and to develop an animal model for further
      investigation of EMRs. MATERIALS AND METHODS: The frequency of TLESRs and
      esophageal body contractions after TLESRs was assessed using ambulatory manometry
      in five healthy individuals and five GERD patients. An animal model was developed
      for reproducible provocation of TLESRs and subsequent EMRs. RESULTS: Patients
      with GERD have significantly more TLESRs than healthy individuals. However, post
      TLESR EMRs were not more frequent in the GERD group. All post-TLESR EMRs
      presented as simultaneous contractions of the esophagus. The feline model allowed
      reproducible initiation of the esophageal motor response after TLESR, showing
      that EMRs can be induced by external mechanoreceptor stimulation simultaneously
      with LES relaxation. This experimental design imitates the conditions after
      fundoplication in humans. CONCLUSIONS: The study demonstrated that GERD patients
      have significantly more TLESRs in comparison with healthy individuals, but these
      were only incidental to EMRs. Further research is needed to improve our
      understanding of esophageal motility disorders. The animal model presented offers
      a feasible tool for investigating TLESR-induced esophageal motility.

PMID- 19577764
TI  - Reducing surgical morbidity by pre-emptive management.

PMID- 19577765
TI  - Traumatic anterior cruciate ligament tear and its implications on meniscal
      degradation: a preliminary novel lapine osteoarthritis model.
AB  - BACKGROUND: Injury patterns of the meniscus following impact trauma resulting in
      anterior cruciate ligament (ACL) rupture are not well understood. This study
      explored the spatial and temporal distribution of meniscal tears in a novel in
      vivo lapine model. METHODS: Skeletally mature Flemish Giant rabbits were
      subjected to either tibiofemoral impaction resulting in ACL rupture or surgical
      ACL transection. Meniscal damage was assessed acutely and after 12 wk for
      traumatically torn, and after 12 wk in ACL transected animals. Morphological
      grading was assessed using previously established criteria, and descriptions of
      meniscal damage were diagnosed by a Board certified orthopedist. Histological
      assessment was also made on 12 wk traumatically torn and ACL transected animals
      using Fast-Green/Safranin-O staining. RESULTS: Traumatic ACL rupture resulted in
      acute tears predominately in the lateral menisci. Animals subjected to both
      surgical transection and traumatic ACL rupture experienced degradation of the
      lateral and medial menisci 12 wk after injury. However, traumatic ACL rupture
      resulted in acute lateral damage and chronic degradation of the menisci, as well
      as more severe degradation of the menisci 12 wk after injury. CONCLUSIONS: This
      study showed that unconstrained high-intensity impacts on the tibiofemoral joint
      lead to meniscal damage in conjunction with ACL ruptures. Both acute and chronic
      changes to the menisci following traumatic impaction were observed. This research
      has implications for the future use of lapine models for osteoarthritis, as it
      incorporates traumatic loading as a more realistic mode contributing to the
      progression of osteoarthritis (OA) compared to surgically transected models.

PMID- 19577766
TI  - Laparoscopy-assisted gastrectomy for early gastric cancer is safe and effective
      in elderly patients.

PMID- 19577767
TI  - CHRNA5 gene D398N polymorphism in Japanese lung adenocarcinoma.
AB  - BACKGROUND: Recently, to identify genetic factors that modify lung cancer risk,
      CHRNA5 non-synonymous variant amino acid position 398 (D398N) was identified. The
      site was a highly conserved in the second cellular loop of the nicotinic
      acetylcholine receptor subunit protein. MATERIALS AND METHODS: We have
      investigated CHRNA5 gene polymorphism status in 302 surgically treated lung
      adenocarcinoma cases from Nagoya City University Hospital. The presence or
      absence of CHRNA5 polymorphism was analyzed by direct sequences. EGFR mutations
      status was already investigated and reported. RESULTS: We detected nine cases
      (2.98%) of CHRNA5 polymorphism (D398N) in our cohort. Total EGFR mutations were
      present in 129 patients (42.7%). The polymorphism statuses were not correlated
      with gender (women; 2.1% versus men; 3.7%, P = 0.5119), smoking status (never
      smoker; 2.0% versus smoker; 4.0%, P = 0.3339), pathological stages (stage I; 2.6%
      versus stage II-IV; 3.8%, P = 0.7246), and EGFR mutation status of the lung
      adenocarcinomas (mutation; 2.3% versus wild type; 3.7%, P = 0.7373). In this
      analysis, CHRNA5 polymorphism (D398N) patients had significantly worse prognosis
      (5/9 were dead; mean survival = 27.1 mo) than the patients with CHRNA5 wild type
      (74/293 were dead; mean survival = 113.9 mo) (log-rank test; P = 0.0146).
      CONCLUSION: Although CHRNA5 polymorphism is rare from Japanese lung cancer,
      polymorphism status might be correlated with shorter survival.

PMID- 19577768
TI  - Outcomes of surgically managed pediatric thyroid cancer.
AB  - BACKGROUND: Thyroid cancer is the most common carcinoma in children, and compared
      with adults, generally present with more advanced disease. Management is similar
      between populations, primarily consisting of total thyroidectomy. With similar
      treatment despite disease severity, we chose to explore the surgical outcome of
      pediatric patients with thyroid malignancy. METHODS: A review of medical records
      at two academic institutions revealed 68 patients<19 y of age who underwent
      surgical resection of a malignant thyroid nodule between 1962 and 2008. RESULTS:
      Of 68 pediatric surgery patients identified with thyroid malignancy, 50 patients
      (74%) had a total thyroidectomy. Minor complications were noted in 21% of
      surgeries with 19% temporary hypocalcemia. Risk of complication was not
      associated with type of surgery. Patients receiving a lobectomy or subtotal
      thyroidectomy were at greater risk for needing a second surgical procedure,
      required by 14 patients (21%). CONCLUSIONS: There was no significant increase in
      surgical complications with respect to type of surgery, however, patients
      receiving less than total thyroidectomy were at increased risk of repeat surgery.
      Total thyroidectomy is recommended as the standard of care for the management of
      pediatric thyroid cancer.

PMID- 19577769
TI  - Acute care surgery program: mentoring fellows and patient outcomes.
AB  - BACKGROUND: Acute care surgery programs have demonstrated that trauma patient
      outcomes have not changed with the addition of emergency general surgery (EGS)
      responsibilities. EGS patient outcomes and the mentoring of fellows on EGS
      service have not been previously studied. We hypothesize that EGS patient
      outcomes would not differ by provider on a service driven by evidence-based
      medicine (EBM) protocols. PATIENTS AND METHODS: Retrospective study of
      prospectively collected EGS repository. academic level I trauma center, and
      regional EGS referral center from 2003 to 2007. There were 14 faculty and seven
      fellows during the study period. EGS coverage is a full week, with weeknight
      coverage by the in-house trauma/EGS faculty. Fellows are mentored by designated
      faculty while on service, who discuss patients, assist in the OR, or assume care
      if necessary. Data collected included age, gender, LOS, ICU LOS, ventilator days,
      disposition (home/rehab), and infectious complications(IC) (VAP, BSI, UTI, SSI).
      Primary outcome was mortality. RESULTS: 1769 patients met study criteria. The
      mean age was 47.1 (+/-18), 47% were males. The average ICU LOS was 2.9 d (+/
      7.9), ventilator d 2.6 (+/-7.6); 82.1% were discharged home and 13.7% were
      referred to rehab. There was no statistical difference in mortality, LOS, ICU
      LOS, disposition, ventilator d, and IC between faculty and fellow providers.
      CONCLUSIONS: An EGS service with EBM protocols assures consistency in patient
      outcomes independent of provider level: faculty or fellows. Our model for
      mentoring fellows did not decrease EGS patient outcomes.

PMID- 19577770
TI  - Despite the increasing use of nonoperative management of firearm trauma, shotgun
      injuries still require aggressive operative management.
AB  - BACKGROUND: The energy dissipation between gunshot and shotgun blasts is very
      different. Injuries from shotgun blasts vary depending on the distance of the
      victim from the shooter, the choke of the shotgun, the pellet load, and the wad
      of the ammunition. We postulated that gunshot and shotgun blasts create different
      injury patterns that dictate different treatment plans. METHODS: Medical records
      of patients with gunshot and shotgun trauma were reviewed from 1998 through 2007
      at our university-based trauma center. Statistical comparisons were made via
      Fisher's test or t-test calculations. RESULTS: We evaluated 2833 patients injured
      by firearms; of these 61 had shotgun wounds (2.2%). The remainder sustained
      gunshot wounds. Mortality between shotgun and gunshot trauma patients was similar
      (7% versus 9%, respectively, P=0.8). There was no difference in the mean Injury
      Severity Score (ISS) (13.7+/-1.6 versus 12.9+/-0.2; P=0.6). Overall, 61% of
      patients underwent operative intervention after shotgun injuries versus 36% of
      patients with gunshot wounds (P<0.0001). Patients surviving shotgun injuries had
      a longer length of stay (10.1+/-2.0 d versus 5.9+/-0.21, P<0.05). CONCLUSIONS:
      Although the injury severity was similar, injuries from shotguns required more
      operations and resource utilization. Shotgun blasts can create impressive
      superficial injuries as well as significant deep organ damage. An aggressive
      operative approach to managing shotgun trauma is advantageous.

PMID- 19577772
TI  - Effect of therapeutic pulsed ultrasound on lipoperoxidation and fibrogenesis in
      an animal model of wound healing.
AB  - Evidence from the literature has shown that the wound healing process is enhanced
      by ultrasound therapy. In the present study, we measured thiobarbituric acid
      reactive substances (TBARS; index of lipoperoxidation) and hydroxyproline (index
      of collagen synthesis) levels in wounds after therapeutic pulsed ultrasound (TPU)
      treatment. Male Wistar rats were submitted to skin ulceration, and three doses of
      TPU (0.4, 0.6, and 0.8W/cm(2)) were used. A circular area of skin was removed
      with a punch biopsy from the medial dorsal region. After TPU for 10 days, TBARS
      (Draper and Hadley [21]) and hydroxyproline (Woessner [22]) levels were measured
      in the tissue around the wound. Results showed that TPU improved wound healing,
      since the wound size was significantly smaller 5 and 10 days after ulceration in
      groups submitted to this treatment. Moreover, TBARS levels were decreased in the
      0.4, 0.6, and 0.8W/cm(2) TPU groups, and hydroxyproline levels were increased in
      the 0.6 and 0.8W/cm(2) TPU groups. These findings indicate that TPU presents
      beneficial effects on the wound healing process, probably by speeding up the
      inflammatory phase and inducing collagen synthesis.

PMID- 19577771
TI  - Wnt5a knock-out mouse as a new model of anorectal malformation.
AB  - BACKGROUND: Anorectal malformations (ARM) represent a variety of congenital
      disorders that involve abnormal termination of the anorectum. Mutations in Shh
      signaling and Fgf10 produce a variety of ARM phenotypes. Wnt signaling has been
      shown to be crucial during gastrointestinal development. We therefore
      hypothesized that Wnt5a may play a role in anorectal development. METHODS: Wild
      type (WT), Wnt5a(+/-) and Wnt5a(-/-) embryos were harvested from timed pregnant
      mice from E15.5 to E18.5, and analyzed for anorectal phenotype. Tissues were
      processed for whole-mount in situ hybridization and histology. RESULTS: Wnt5a is
      expressed in the embryonic WT colon and rectum. Wnt5a(-/-) mutants exhibit
      multiple deformities including anorectal malformation. A fistula between the
      urinary and intestinal tracts can be identified as early as E15.5. By E18.5, the
      majority of the Wnt5a(-/-) mutants display a blind-ending pouch of the distal
      gut. CONCLUSIONS: The expression pattern of Wnt5a and the ARM phenotype seen in
      Wnt5a(-/-) mutants demonstrate the critical role of Wnt5a during anorectal
      development. This study establishes a new model of ARM involving the Wnt5a
      pathway.

PMID- 19577773
TI  - Superior divisional vestibular paresis in anterior inferior cerebellar artery
      infarction.
AB  - A 74-year-old woman with sudden vertigo and dysarthria showed spontaneous
      nystagmus beating rightward, upward and clockwise. She also exhibited dysfunction
      of the left utricle and superior and horizontal canals, which was documented by
      head impulse and heave tests, measurements of ocular torsion and subjective
      visual vertical tilt, bithermal caloric tests, and rotation axis analysis of the
      spontaneous nystagmus. In contrast, functions of the left posterior canal,
      saccule, and cochlea were remained intact, as evidenced by normal head impulse
      test, audiometry and vestibular evoked myogenic potential. MRI revealed an acute
      infarction in the left lateral pons of anterior inferior cerebellar artery (AICA)
      territory. Our patient with AICA infarction showed isolated damage to the
      superior vestibular labyrinth or its afferents with preservation of the inferior
      vestibular labyrinth and auditory function. Our patient provides further evidence
      that isolated damage to the superior vestibular labyrinth or its afferents may be
      a mechanism of isolated vascular vertigo.

PMID- 19577774
TI  - Serial retinal fluorescein angiography and immune therapy in Susac's syndrome.
AB  - We report a patient with Susac's disease presenting classically in a young female
      with an encephalopathy and visual disturbance with later deafness and tinnitus.
      Her encephalopathy settled, but subsequent serial fluorescein angiograms allowed
      sensitive monitoring of continuing sub-clinical disease activity, and provide
      evidence of a clear therapeutic response to immune suppression with tacrolimus
      (but not steroids alone)--and of a lack of efficacy of nimodipine and aspirin. We
      believe this single case study has both pathogenetic and useful practical
      implications: the apparently favourable response to immunosuppression lends
      support to the hypothesis that Susac's Syndrome is an immune-mediated disease;
      while the presence during symptomatic clinical remission of sporadic, multi-focal
      episodes of hyper-fluorescence, suggestive of breakthrough vasculopathy despite
      treatment, underlines the fact that the natural history of this rare condition is
      still not fully understood. Fluorescein angiography is proposed as a sensitive
      and important approach to the monitoring of sub-clinical disease activity, and so
      optimising immune suppressive treatment.

PMID- 19577775
TI  - Occurrence of brominated flame retardants, polycyclic musks, and chlorinated
      naphthalenes in seal blubber from Antarctica: comparison to organochlorines.

PMID- 19577776
TI  - [A patient from Maghreb with dysphagia].

PMID- 19577777
TI  - [Giant cell tumor of the distal humerus].

PMID- 19577779
TI  - [Polyostotic fibrous dysplasia of the thoracic spine. A case study and review of
      the literature].
AB  - Polyostotic fibrous dysplasia of the thoracic spine is extremely rare and
      considered a benign disease. We report the case of a 46-year-old woman admitted
      to the emergency department for subacute paraplegia. The spinal X-ray showed a
      spontaneous fracture at the T4-T5 level. The CT scan revealed a tumor
      infiltration of the vertebral body responsible for lysis. Spinal MRI confirmed
      the neoplasia also located in the epidural space with spinal cord compression.
      The patient underwent an emergency laminectomy associated with transpedicular
      screw fixation between the T2 and T6 levels. At 2 months, she had evolved to a
      normal gait. In the second session, a transthoracic approach was used for a bone
      graft-assisted fusion procedure to achieve long-term stabilization. At 4 years,
      the bone fusion was excellent and the patient was able to resume
      socioprofessional activities. The diagnosis of fibrous dysplasia is usually made
      histologically on surgical biopsy but MRI and CT scan sometimes provide a
      preliminary indication. Although a consensus for management of this disease has
      not been achieved, the authors recommend radical removal of all involved tissues
      accompanied by internal fixation and bone-graft-assisted fusion.

PMID- 19577778
TI  - Evaluation of gremlin 1 (GREM1) as a candidate susceptibility gene for
      albuminuria-related traits in Mexican Americans with type 2 diabetes mellitus.
AB  - Several novel genes that are up-regulated in the kidney in diabetes have been
      identified including GREM1, which encodes gremlin 1. GREM1 maps to human
      chromosome 15q12, a region previously found to be linked to albumin to creatinine
      ratio (ACR) in Mexican Americans. The objective of this study is to investigate
      whether genetic variants in GREM1, a positional candidate gene, contribute to
      variation in ACR. By sequencing 32 individuals for both exons and 2-kilobase
      putative promoter region of GREM1, we identified 19 genetic variants including 5
      in the promoter region and 13 in the 3' untranslated region. Of 19 polymorphisms
      identified, 13 polymorphisms were genotyped in the entire cohort (N = 670, 39
      large families) either by restriction fragment length polymorphism or by TaqMan
      (Applied Biosystems, Foster City, CA) assays. Association analyses between the
      genotypes and ACR, type 2 diabetes mellitus, and related phenotypes were carried
      out using a measured genotype approach as implemented in the variance component
      analytical tools (SOLAR). Of the variants examined for association, none
      exhibited statistically significant association with ACR after accounting for the
      effects of covariates such as age, sex, diabetes, duration of diabetes, systolic
      blood pressure, and antihypertensive medications. However, 2 novel variants at
      the 3' untranslated region showed significant association with estimated
      glomerular filtration rate (P = .010 and P = .049) and body mass index (P = .013
      and P = .019) after accounting for trait-specific covariate influences.
      Furthermore, a novel variant located in the promoter exhibited a significant
      association with systolic (P = .038) and diastolic blood pressure (P = .005)
      after adjusting for the effects of age, sex, diabetes, and antihypertensive
      medications. In conclusion, the variants examined at GREM1 are not significant
      contributors to variation in ACR in Mexican Americans, although they appear to
      minimally influence risk factors related to ACR.

PMID- 19577780
TI  - Benzoxazinoid biosynthesis, a model for evolution of secondary metabolic pathways
      in plants.
AB  - Benzoxazinoids are secondary metabolites that are effective in defence and
      allelopathy. They are synthesised in two subfamilies of the Poaceae and
      sporadically found in single species of the dicots. The biosynthesis is fully
      elucidated in maize; here the genes encoding the enzymes of the pathway are in
      physical proximity. This "biosynthetic cluster" might facilitate coordinated gene
      regulation. Data from Zea mays, Triticum aestivum and Hordeum lechleri suggest
      that the pathway is of monophyletic origin in the Poaceae. The branchpoint from
      the primary metabolism (Bx1 gene) can be traced back to duplication and
      functionalisation of the alpha-subunit of tryptophan synthase (TSA). Modification
      of the intermediates by consecutive hydroxylation is catalysed by members of a
      cytochrome P450 enzyme subfamily (Bx2-Bx5). Glucosylation by an UDP
      glucosyltransferase (UGT, Bx8, Bx9) is essential for the reduction of
      autotoxicity of the benzoxazinoids. In some species 2,4-dihydroxy-1,4-benzoxazin
      3-one-glucoside (DIBOA-glc) is further modified by the 2-oxoglutarate-dependent
      dioxygenase BX6 and the O-methyltransferase BX7. In the dicots Aphelandra
      squarrosa, Consolida orientalis, and Lamium galeobdolon, benzoxazinoid
      biosynthesis is analogously organised: The branchpoint is established by a
      homolog of TSA, P450 enzymes catalyse hydroxylations and at least the first
      hydroxylation reaction is identical in dicots and Poaceae, the toxic aglucon is
      glucosylated by an UGT. Functionally, TSA and BX1 are indole-glycerolphosphate
      lyases (IGLs). Igl genes seem to be generally duplicated in angiosperms.
      Modelling and biochemical characterisation of IGLs reveal that the catalytic
      properties of the enzyme can easily be modified by mutation. Independent
      evolution can be assumed for the BX1 function in dicots and Poaceae.

PMID- 19577781
TI  - High frequency shear horizontal plate acoustic wave devices.
AB  - It has been shown recently that shear horizontal acoustic waves propagating in
      piezoelectric plates whose thickness h is much less than the acoustic wavelength
      lambda possess a number of attractive properties for use in sensor and signal
      processing applications. In order to exploit the potential benefits of these
      waves, however, one needs to fabricate devices on very thin plates. We have
      developed a suitable fabrication method which can be used to realize devices on
      such thin plates. In this method, the device is first fabricated on a plate of
      normal thickness (approximately 500 microm) and the substrate is then lapped from
      the back side to reduce the thickness. The technique has been utilized to realize
      devices on plates of thickness less than 70 microm. A shear horizontal plate
      acoustic wave (SH-PAW) delay line of fundamental resonant frequency greater than
      25 MHz and insertion loss less than 7 dB has been realized on a 60 microm thick Y
      -cut, X--propagation lithium niobate substrate. The device also shows strong
      response near the third harmonic frequency of 75 MHz.

PMID- 19577782
TI  - Host-dependent roles of the viral 5' untranslated region (UTR) in RNA
      stabilization and cap-independent translational enhancement mediated by the 3'
      UTR of Red clover necrotic mosaic virus RNA1.
AB  - The genome of Red clover necrotic mosaic virus (RCNMV) consists of RNA1 and RNA2,
      both lacking a cap structure and a poly(A)tail. RNA1 has a translational enhancer
      element (3'TE-DR1) in the 3' untranslated region (UTR). In this study, we
      analyzed the roles of 5' and 3' UTRs of RNA1 in 3'TE-DR1-mediated cap-independent
      translation in cowpea and tobacco BY-2 protoplasts using a dual-luciferase (Luc)
      reporter assay system. Most mutations introduced into RNA1 5' UTR in reporter Luc
      mRNA abolished or greatly reduced cap-independent translation in BY-2
      protoplasts, whereas those mutations had no or much milder effects if any on
      translational activity in cowpea protoplasts. Our results suggest that a stem
      loop structure predicted in the 5' proximal region of RNA1 plays important roles
      in both translation and RNA stability. We also show that 3'TE-DR1-mediated cap
      independent translation relies on a ribosome-scanning mechanism in both
      protoplasts.

PMID- 19577783
TI  - Impact of natural organic matter and divalent cations on the stability of aqueous
      nanoparticles.
AB  - The stability of nanoparticles in aquatic environment plays an important role in
      determining their environmental implication and potential risk to human health.
      This research studied the impact of natural organic matter (NOM) and divalent
      cations (Ca(2+)) on the stability of engineered metal oxide nanoparticles (e.g.
      ZnO, NiO, TiO(2), Fe(2)O(3) and SiO(2)). When nanoparticles were present in
      neutral water, a relatively weak electrolyte concentration (0.01 M KCl) could
      result in their aggregation; however, with the addition of 1 mg/L NOM, the
      negative surface charge of nanoparticles increased significantly and therefore
      their propensity to aggregate is reduced. 4 mg/L NOM stabilized most
      nanoparticles by producing -30 mV or higher zeta potentials. On the other hand,
      the negative charge that NOM imparted to nanoparticles could be neutralized by
      divalent cations (calcium ions). 0.04 M-0.06 M Ca(2+) induced the aggregation of
      NOM-coated nanoparticles. It should be noted that among all the studied
      nanoparticles, SiO(2) exhibited the unique stability due to its low NOM
      adsorption capacity and small Hamaker constant. SiO(2) remained stable no matter
      whether the solution contained NOM or Ca(2+).

PMID- 19577784
TI  - Chloroform in indoor swimming-pool air: monitoring and modeling coupled with the
      effects of environmental conditions and occupant activities.
AB  - Human exposure to chloroform in indoor swimming pools has been recognized as a
      potential health concern. Although environmental monitoring is a useful technique
      to investigate chloroform concentrations in indoor swimming-pool air, in
      practice, the interpretations of measured data would inevitably run into
      difficulties due to the complex interactions among the numerous variables,
      including environmental conditions and occupant activities. Considering of the
      relevant variables of environmental conditions and occupant activities, a
      mathematical model was first proposed to predict the chloroform concentration in
      indoor swimming-pool air. The developed model provides a straightforward,
      conceptually simple way to predict the indoor air chloroform concentration by
      calculating the mass flux, J, and the Peclet number, Pe, and by using a heuristic
      value of the indoor airflow recycle ratio, R. The good agreement between model
      simulation and measured data demonstrates the feasibility of using the presented
      model for indoor air quality management, operational guidelines and health
      related risk assessment.

PMID- 19577785
TI  - Stabilization of highly concentrated suspensions of iron nanoparticles using
      shear-thinning gels of xanthan gum.
AB  - Nanoscale zerovalent iron (NZVI) particles have recently become subject of great
      interest in the field of groundwater remediation for their ability to treat a
      wide variety of organic and inorganic contaminants. However, the field
      application of this technology is strongly hindered by the lack of stability of
      NZVI water suspensions. This study demonstrates that highly concentrated NZVI
      slurries (15g/L) can be stabilized for more than 10 days adding 6g/L of xanthan
      gum biopolymer. Stability against aggregation and sedimentation was achieved in
      the range of ionic strength 6 x 10(-3)-12 mM and is mainly due to the formation
      of a viscous gel characterized by shear-thinning behaviour.

PMID- 19577786
TI  - Preparation and evaluation of iron-chitosan composites for removal of As(III) and
      As(V) from arsenic contaminated real life groundwater.
AB  - A study on the removal of arsenic from real life groundwater using iron-chitosan
      composites is presented. Removal of arsenic(III) and arsenic(V) was studied
      through adsorption at pH 7.0 under equilibrium and dynamic conditions. The
      equilibrium data were fitted to Langmuir adsorption models and the various model
      parameters were evaluated. The monolayer adsorption capacity from the Langmuir
      model for iron chitosan flakes (ICF) (22.47+/-0.56 mg/g for As(V) and 16.15+/
      0.32 mg/g for As(III)) was found to be considerably higher than that obtained for
      iron chitosan granules (ICB) (2.24+/-0.04 mg/g for As(V); 2.32+/-0.05 mg/g for
      As(III)). Anions including sulfate, phosphate and silicate at the levels present
      in groundwater did not cause serious interference in the adsorption behavior of
      arsenate/arsenite. The column regeneration studies were carried out for two
      sorption-desorption cycles for both As(III) and As(V) using ICF and ICB as
      sorbents. One hundred and forty-seven bed volumes of As(III) and 112 bed volumes
      of As(V) spiked groundwater were treated in column experiments using ICB,
      reducing arsenic concentration from 500 to <10 microg/l. The eluent used for the
      regeneration of the spent sorbent was 0.1M NaOH. The adsorbent was also
      successfully applied for the removal of total inorganic arsenic down to <10
      microg/l from real life arsenic contaminated groundwater samples.

PMID- 19577787
TI  - Identification and chemical characterization of specific organic constituents of
      petrochemical effluents.
AB  - Based on extensive GC/MS screening analyses, the molecular diversity of
      petrochemical effluents discharged to a river in North Rhine-Westphalia was
      characterised. Within a wide spectrum of organic wastewater constituents,
      specific compounds that might act as source indicators have been determined. This
      differentiation was based on (i) the individual molecular structures, (ii) the
      quantitative appearance of organic compounds in treated effluents and (iii) the
      information on their general occurrence in the technosphere and hydrosphere.
      Principally, site-specific indicators have been distinguished from candidates to
      act as general petrochemical indicators. Further on, monitoring the environmental
      behaviour of target organic contaminants in an aquatic system shortly after their
      release into the river allowed a first evaluation of the impact of the petrogenic
      emission in terms of the quantity and spatial distribution. The identification of
      petrogenic contaminants was not restricted to constituents of the effluents only,
      but comprised the compounds circulating in the wastewater systems within a
      petrochemical plant. A number of environmentally relevant and structurally
      specific substances that are normally eliminated by wastewater treatment
      facilities were identified. Insufficient wastewater treatment, careless waste
      handling or accidents at industrial complexes are potential sources for a single
      release of the pollutants. This study demonstrates the relevance of source
      specific organic indicators to be an important tool for comprehensive assessment
      of the potential impact of petrochemical activities to the contamination of an
      aquatic environment.

PMID- 19577788
TI  - Performance of CHROMagar Staph aureus and CHROMagar MRSA for detection of
      Staphylococcus aureus in seawater and beach sand--comparison of culture,
      agglutination, and molecular analyses.
AB  - Beach seawater and sand were analyzed for Staphylococcus aureus and methicillin
      resistant S. aureus (MRSA) for samples collected from Avalon, and Doheny Beach,
      CA. Membrane filtration followed by incubation on CHROMagar Staph aureus (SCA)
      and CHROMagar MRSA (C-MRSA) was used to enumerate S. aureus and MRSA,
      respectively. Media performance was evaluated by comparing identification via
      colony morphology and latex agglutination tests to PCR (clfA, 16S, and mecA
      genes). Due to background color and crowding, picking colonies from membrane
      filters and streaking for isolation were sometimes necessary. The specificity of
      SCA and C-MRSA was improved if colony isolates were identified by the presence of
      a matte halo in addition to mauve color; however routine agglutination testing of
      isolates did not appear warranted. Using the appearance of a colony on the
      membrane filter in conjunction with isolate appearance, the positive % agreement,
      the negative % agreement, and the % positive predictive accuracy for SCA was 84%,
      95%, and 99% respectively, and for C-MRSA it was 85%, 98%, and 92%, respectively.
      Sensitivity and specificity of SCA and C-MRSA with membrane-filtered beach
      samples were optimized through identification experience, control of filter
      volume and incubation time, and isolation of colonies needing further
      identification. With optimization, SCA and C-MRSA could be used for enumeration
      of S. aureus and MRSA from samples of beach water and sand. For the sites studied
      here, the frequency of detection of S. aureus ranged from 60 to 76% and 53 to 79%
      for samples of beach seawater and sand, respectively. The frequency of detection
      of MRSA ranged from 2 to 9% and 0 to 12% for samples of seawater and sand,
      respectively.

PMID- 19577789
TI  - Proteomic analysis of chromate-induced modifications in Pseudokirchneriella
      subcapitata.
AB  - In this work, we have analyzed the changes in the protein expression profile
      elicited by chromium (Cr) exposure in the freshwater green alga
      Pseudokirchneriella subcapitata, a well known bio-indicator of water pollution.
      We tested two experimental conditions, namely 0.2 and 1ppm of potassium
      dichromate; this concentration range includes the environmentally-relevant
      concentrations. Results show that neither concentration of potassium dichromate
      tested inhibited algal growth. However, the proteomic approach allowed the
      identification of relevant modifications in protein expression. In fact, among
      800 protein spots detected by two-dimensional electrophoresis, 16 Cr-regulated
      proteins, including predicted and novel ones, were identified using tandem mass
      spectromic protein analysis. The results demonstrate a Cr-specific action in
      altering several photosynthetic proteins, such as ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO), RuBisCO activase, Light Harvesting Chla/b
      protein complex, and stress related Chla/b binding protein1. Although Cr toxicity
      with respect to photosynthesis has been already documented, here we have
      identified, for the first time, the target proteins of this toxicity. Cr also
      induced a modulation of some proteins involved in the metabolism of the amino
      acids glutamine, arginine and methionine. These data are supported by changes in
      cellular polyamine (PA) accumulation. Present findings provide new insight into
      the molecular mechanisms underlying Cr toxicity in P. subcapitata.

PMID- 19577790
TI  - Effects of 2,4-dichlorophenoxyacetic acid formulation on medulla spinalis of
      Poecilia reticulata: a histopathological study.
AB  - This study investigated the possible effects of a commonly used foliar herbicide
      2,4-dichlorophenoxyacetic acid (2,4-D) formulation on medulla spinalis of
      lebistes. Fish were exposed to 2,4-D (15, 30, 45 mg L(-1)), behavioral changes
      were monitored. Fish were fixed, histopathological examination was carried out on
      sections taken from the upper parts of the fish body. Histopathology showed
      increase in neuronal loss, swelling indicating formation of intracellular edema,
      vacuolization noticed as the formation of vacuoles within or adjacent to cells,
      deformation in the Nissl granules, pyknosis and gliosis in medulla spinalis.
      Behavioral changes were decreased general activity, grouping, shortness in
      breath, sudden rotations and jumping, loss of equilibrium and colour. In
      conclusion, this commercial formulation of 2,4-D is considerably neurotoxic to
      lebistes. Fish constitute the last link in the chain of the feeding cycle in
      aquatic eco-system, number of studies investigating acute and chronic
      neurotoxicity of various herbicides in fish should be increased.

PMID- 19577791
TI  - Characterizing the release of different composition of dissolved organic matter
      in soil under acid rain leaching using three-dimensional excitation-emission
      matrix spectroscopy.
AB  - Although excitation-emission matrix spectroscopy (EEMS) has been widely used to
      characterize dissolved organic matter (DOM), there has no report that EEMS has
      been used to study the effects of acid rain on DOM and its composition in soil.
      In this work, we employed three-dimensional EEMS to characterize the compositions
      of DOM leached by simulated acid rain from red soil. The red soil was subjected
      to leaching of simulated acid rain of different acidity, and the leached DOM
      presented five main peaks in its EEMS: peak-A, related to humic acid-like (HA
      like) material, at Ex/Em of 310-330/395-420nm; peak-B, related to UV fulvic acid
      like (FA-like) material, at Ex/Em of 230-280/400-435nm; peak-C and peak-D, both
      related to microbial byproduct-like material, at Ex/Em of 250-280/335-355nm and
      260-280/290-320nm, respectively; and peak-E, related to simple aromatic proteins,
      at Ex/Em of 210-240/290-340nm. EEMS analysis results indicated that most DOM
      could be lost from red soil in the early phase of acid rain leaching. In addition
      to the effects of the pH of acid rain, the loss of DOM also depended on the
      properties of its compositions and the solubility of their complexes with
      aluminum. HA-like and microbial byproduct-like materials could be more easily
      released from red soil by acid rain at both higher pH (4.5 and 5.6) and lower pH
      (2.5 and 3) than that at middle pH (3.5). On the contrary, FA-like material lost
      in a similar manner under the action of different acid rains with pH ranging from
      2.5 to 5.6.

PMID- 19577792
TI  - Comparison of UASB and EGSB performance on the anaerobic biodegradation of 2,4
      dichlorophenol.
AB  - The anaerobic degradation of 2,4-dichlorophenol (2,4-DCP) in upflow anaerobic
      sludge blanket (UASB) and expanded granular sludge bed (EGSB) reactors using
      glucose as main carbon source was studied. The performance of both systems was
      compared in terms of 2,4-DCP and COD removal efficiencies, methane production,
      stability, granular sludge adaptability as well as reversion of the bacterial
      inhibition. Both organic and 2,4-DCP loading rates were incrementally varied
      through the experiments. With loading rates of 1.9 gCODL(-1)d(-1) and 100mg 2,4
      DCP L(-1)d(-1), 75% and 84% removal efficiencies of this compound, accompanied by
      COD consumption efficiencies of 61% and 80% were achieved in the UASB and EGSB
      reactors, respectively. In these conditions, methane production reached 0.088 L
      CH(4)g(-1) COD in the EGSB reactor whereas in the UASB reactor was almost
      negligible. Decreasing the 2,4-DCP loading rate to 30 mgL(-1)d(-1) an improvement
      in the methane production was observed in both reactors (methanogenic activity of
      0.148 and 0.192 L CH(4)g(-1) COD in UASB and EGSB reactors, respectively).
      Efficiency of dechlorination was improved in both reactors from around 30% to 80%
      by reducing to one-half the COD due to a decreasing of the 4-chlorophenol
      concentration accumulated in the effluents of both reactors. The dechlorination
      efficiency of the UASB reactor was dramatically inhibited at a 2,4-DCP feed
      concentration above around 210 mgL(-1) because of 2,4-DCP accumulation in the
      effluent. SEM studies revealed no significant morphological changes in the sludge
      granules.

PMID- 19577793
TI  - Influence of temperature and soil type on the toxicity of three pesticides to
      Eisenia andrei.
AB  - Expansion of agriculture in the tropics has increased the use of pesticides that
      may affect the soil ecosystems. Few studies so far determined the effects of
      pesticides in the tropics and tropical risk assessment therefore often relies on
      data from temperate conditions. Hence we compared the toxicity of chlorpyrifos,
      carbofuran and carbendazim to the earthworm Eisenia andrei at two different
      temperatures reflecting temperate and tropical conditions. The toxicity of the
      three pesticides in both conditions decreased in the order
      carbendazim>carbofuran>chlorpyrifos. For chlorpyrifos and carbofuran, but not for
      carbendazim, survival was more sensitive at the higher temperature, probably due
      to increased earthworm activity. Sub-lethal effects (reproduction and growth)
      however, varied inconsistently with temperature and soil types. We conclude that
      toxicity of pesticides in tropics may not be predicted from data generated under
      temperate conditions, even within the same species.

PMID- 19577794
TI  - Applying indoor and outdoor modeling techniques to estimate individual exposure
      to PM2.5 from personal GPS profiles and diaries: a pilot study.
AB  - Impacts of individual behavior on personal exposure to particulate matter (PM)
      and the associated individual health effects are still not well understood. As
      outdoor PM concentrations exhibit highly temporal and spatial variations,
      personal PM exposure depends strongly on individual trajectories and activities.
      Furthermore, indoor environments deserve special attention due to the large
      fraction of the day people spend indoors. The indoor PM concentration in turn
      depends on infiltrated outdoor PM and indoor particle sources, partially caused
      by the activities of people indoor. We present an approach to estimate PM2.5
      exposure levels for individuals based upon existing data sources and models. For
      this pilot study, six persons kept 24-hour diaries and GPS tracks for at least
      one working day and one weekend day, providing their daily activity profiles and
      the associated geographical locations. The survey took place in the city of
      Munster, Germany in the winter period between October 2006 and January 2007.
      Environmental PM2.5 exposure was estimated by using two different models for
      outdoor and indoor concentrations, respectively. For the outdoor distribution, a
      dispersion model was used and extended by actual ambient fixed site measurements.
      Indoor concentrations were modeled using a simple mass balance model with the
      estimated outdoor concentration fraction infiltrated and indoor activities
      estimated from the diaries. A limited number of three 24-hour indoor measurements
      series for PM were performed to test the model performance. The resulting average
      daily exposure of the 14 collected profiles ranged from 21 to 198 microg m(-3)
      and showed a high variability over the day as affected by personal behavior. Due
      to the large contribution of indoor particle sources, the mean 24-hour exposure
      was in most cases higher than the daily means of the respective outdoor fixed
      site monitors. This feasibility study is a first step towards a more
      comprehensive modeling approach for personal exposure, and therefore restricted
      to limited data resources. In future, this model framework not only could be of
      use for epidemiological research, but also of public interest. Any individual
      operating a GPS capable device may become able to obtain an estimate of its
      personal exposure along its trajectory in time and space. This could provide
      individuals a new insight into the influence of personal habits on their exposure
      to air pollution and may result in the adaptation of personal behavior to
      minimize risks.

PMID- 19577795
TI  - The value of perioperative imaging in patients with uterine sarcomas.
AB  - OBJECTIVE: To explore the yield and impact of perioperative imaging on management
      among patients undergoing surgical resection and treatment of uterine sarcomas.
      METHODS: A retrospective chart review was done for women with histologically
      confirmed uterine sarcomas treated at Barnes Jewish Hospital/Washington
      University from 2001 to 2007. Descriptive statistics, Cox multivariate models,
      and Kaplan-Meier plots were used to evaluate associations and survival. RESULTS:
      A total of 92 patients were identified and 55 (60%) were diagnosed with stage III
      IV disease. Perioperative imaging was obtained in 84 (91%) cases, including chest
      X-ray in 66 (72%), computerized tomography (CT) of the abdomen and pelvis in 59
      (64%), chest CT in 33 (36%), positron emission tomography (PET) in 8 (9%), and CT
      of the head, pelvic magnetic resonance imaging (MRI), or bone scan in a total of
      2 (2.2%). Imaging identified abnormalities concerning for metastases in 30 (32%)
      studies. Thirty-four recurrences have been documented, and 21 (62%) of these
      treatment failures were extrapelvic. Multivariate analysis of this series noted
      that tomographic evidence of extrauterine disease predicted recurrence (p=0.028)
      and incomplete surgical resection (p=0.003, HR 6.0 95% CI 1.9-19.9) predicted
      disease-free survival. Imaging contributed to change in surgical and post
      surgical treatment decisions in 8 (9%) patients. CONCLUSION: Pretreatment imaging
      studies change management in a minority of patients with newly diagnosed uterine
      sarcomas.

PMID- 19577796
TI  - Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant
      ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group
      trial.
AB  - BACKGROUND: 2-Methoxyestradiol (Panzem, 2ME2) is an endogenous metabolite of
      estradiol that destabilizes microtubules and exerts anti-angiogenic properties.
      This study was conducted to determine the activity and safety of 2ME2
      administered as a NanoCrystal dispersion (NCD) formulation in patients with
      recurrent, platinum-resistant epithelial ovarian cancer (EOC). METHODS: Eligible
      patients had relapsed, platinum-resistant or refractory EOC with measurable or
      detectable disease. There was no limit on the number of prior treatment regimens.
      2ME2 NCD 1000 mg orally four times daily (q.i.d.) was administered continuously
      during 4 week cycles. The primary endpoint was objective response rate (ORR).
      Secondary endpoints were assessment of toxicity, rate of clinical benefit defined
      as the number of patients experiencing an objective response, a CA125 response or
      stable disease (SD) >3 months, mean change in CA-125, progression-free survival
      (PFS), and pharmacokinetic analyses of 2ME2. RESULTS: Eighteen patients were
      enrolled. Median age was 65.5 (range 40-73). Patients had received a median of
      five prior treatments. The most common adverse events were fatigue (78%), nausea
      (78%), diarrhea (39%), neuropathy (50%), edema (39%), and dyspnea (44%), the
      majority being grade 1-2. There were no objective responses, but seven patients
      had SD as best response. Of those, two patients had SD for greater than 12
      months. The rate of clinical benefit was 31.3%. Fairly stable plasma levels of
      2ME2 ranging within the predicted therapeutic window were observed. CONCLUSIONS:
      The NCD formulation of 2ME2 is well tolerated in patients with heavily pretreated
      EOC. Few of these heavily pretreated patients had sustained stable disease.

PMID- 19577797
TI  - Urinary hormone analysis assists reproductive monitoring and sex identification
      of bell frogs (Litoria raniformis).
AB  - With the world currently facing a global amphibian extinction crisis, the
      development of techniques to help meet the needs of conservation managers and
      researchers studying the reproductive biology of amphibians is needed. Here, we
      developed enzyme immunoassays to measure estrone, testosterone, and progesterone
      hormone metabolites in the urine of Litoria raniformis, the southern bell frog.
      Concentrations of urinary estrone, testosterone, and progesterone increased
      during the breeding season for females (P<0.05). Concentrations of urinary
      testosterone and progesterone increased for males during the breeding season
      compared with that for months where no reproductive behaviors were observed
      (P<0.05). Furthermore, urinary estrone concentrations proved to be a reliable
      sexing tool for adult frogs, with no overlap between the sexes in 98% of cases,
      regardless of season. There was no difference in estrone (P=0.204) or
      testosterone (P=0.485) metabolite concentrations between samples taken
      immediately upon capture and those taken 12 to 24h later from the same
      individual. Progesterone metabolite concentrations were lower on Day 2 than upon
      collection (P=0.004). This is the first study to show that urinary hormone
      analysis can be a useful technique for reproductive monitoring in an amphibian.
      Additionally, hormone metabolite measures offer promise as sex identification
      tools for monomorphic species and for those whose secondary sex characteristics
      are visible only during the breeding season.

PMID- 19577799
TI  - NSAIDs and aspirin: notorious or FAMOUS?

PMID- 19577798
TI  - Famotidine for the prevention of peptic ulcers and oesophagitis in patients
      taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: There are few therapeutic options for the prevention of
      gastrointestinal mucosal damage caused by low-dose aspirin. We therefore
      investigated the efficacy of famotidine, a well-tolerated histamine H(2)-receptor
      antagonist, in the prevention of peptic ulcers and erosive oesophagitis in
      patients receiving low-dose aspirin for vascular protection. METHODS: Adult
      patients (aged >/=18 years) from the cardiovascular, cerebrovascular, and
      diabetes clinics at Crosshouse Hospital, Kilmarnock, UK, were eligible for
      enrolment in this phase III, randomised, double-blind, placebo-controlled trial
      if they were taking aspirin 75-325 mg per day with or without other
      cardioprotective drugs. Patients without ulcers or erosive oesophagitis on
      endoscopy at baseline were randomly assigned by computer-generated randomisation
      sequence to receive famotidine 20 mg twice daily (n=204) or placebo twice daily
      (n=200). Patients had a final endoscopic examination at 12 weeks. The primary
      endpoint was the development of new ulcers in the stomach or duodenum or erosive
      oesophagitis at 12 weeks after randomisation. Analysis was by intention to treat,
      including all randomised patients who received at least one dose of study drug
      (famotidine or placebo). This trial is registered as an International Standard
      Randomised Clinical Trial, number ISRCTN96975557. FINDINGS: All randomised
      patients received at least one dose and were included in the ITT population. 82
      patients (famotidine, n=33; placebo, n=49) did not have the final endoscopic
      examination and were assumed to have had normal findings; the main reason for
      participant withdrawal was refusal to continue. At 12 weeks, comparing patients
      assigned to famotidine with patients assigned to placebo, gastric ulcers had
      developed in seven (3.4%) of 204 patients compared with 30 (15.0%) of 200
      patients (odds ratio [OR] 0.20, 95% CI 0.09-0.47; p=0.0002); duodenal ulcers had
      developed in one (0.5%) patient compared with 17 (8.5%; OR 0.05, 0.01-0.40;
      p=0.0045); and erosive oesophagitis in nine (4.4%) compared with 38 (19.0%; OR
      0.20, 0.09-0.42; p<0.0001), respectively. There were fewer adverse events in the
      famotidine group than in the placebo group (nine vs 15); four patients in the
      placebo group were admitted to hospital with upper gastrointestinal haemorrhage.
      The other most common adverse event was angina (famotidine, n=2; placebo, n=4).
      INTERPRETATION: Famotidine is effective in the prevention of gastric and duodenal
      ulcers, and erosive oesophagitis in patients taking low-dose aspirin. These
      findings widen the therapeutic options for the prevention of gastrointestinal
      damage in patients needing vascular protection. FUNDING: Merck Laboratories and
      Astellas Pharma.

PMID- 19577800
TI  - Regulation of polyurethane hemocompatibility and endothelialization by tethered
      hyaluronic acid oligosaccharides.
AB  - Current synthetic vascular grafts possess a significant mechanical mismatch
      compared to the native vasculature and do not permit endothelialization; both of
      these deficiencies contribute to the relatively high rate of failure of many
      synthetic grafts. In this communication, we report the modification of
      polyurethane (PU)-based materials to impart hemocompatibility, support
      endothelial growth, and display vascular-appropriate mechanics. This modification
      was achieved by incorporating branched polyethylenimine (PEI) into the PU
      backbone, followed by covalent attachment of either hyaluronic acid (HA; 4.7, 64,
      and 104 kDa), heparin, or poly(ethylene glycol) (PEG; used as a non-adhesive
      control) to the PEI. This grafting chemistry resulted in comparatively dense
      immobilization of HA and heparin (0.062 and 2.3 microg/cm(2), respectively) to
      the PU-PEI surfaces. PU materials modified with HA were more effective than
      either PEG- or heparin-grafted materials with respect to limiting protein
      adsorption and platelet adhesion. Confluent, morphologically-healthy cultures of
      endothelial cells were achieved only on materials grafted with low molecular
      weight HA, but not high MW HA, heparin, or PEG. These modifications in PU
      chemistry were performed while retaining material mechanics in the range of
      native vascular tissue. Thus, this study describes the generation of materials
      that possess the unique ability to display excellent hemocompatibility while
      simultaneously supporting extensive endothelialization and retaining vascular
      appropriate mechanics. The bioactivity of these materials was regulated by the
      molecular weight of the grafted HA, and their physical and biological properties
      make them promising for use as vascular grafts.

PMID- 19577801
TI  - Elaboration of radiopaque iodinated nanoparticles for in situ control of local
      drug delivery.
AB  - Drug delivery systems can benefit from intrinsic radiopacity as this property
      will allow following up the diffusion path of the nanoparticles containing the
      therapeutic drug after their local administration. Herein, we report the
      synthesis of iodinated derivatives of cellulose acetate (CA) and their
      formulation into aqueous radiopaque nanoparticle suspensions. Modification and
      purification of CA with mono- or tri-iodobenzoyl chloride were characterized by
      NMR spectroscopy and elemental analysis of iodine. In particular, measurements of
      diffusion coefficients by the DOSY 2D NMR method allowed controlling the complete
      elimination of non-grafted iodinated materials. Pure radiopaque CA was
      successfully achieved with an iodine content varying between 14 and 32%. Aqueous
      suspensions of nanoparticles were successfully formed, characterized by being
      spherical, <100 nm in size and stable as a suspension over 3 months. The degree
      of substitution, in particular the triiodo moieties, imparted a good level of
      radiopacity whether in dry powder form (2627 HU) or as a nanoparticle suspension
      (298 HU). These values are comparable to radiopacity of systems reported in
      literature to be in vivo visible. Loading of paclitaxel was successfully
      attempted, suggesting that the developed radiopaque nanoparticles can ultimately
      function as a drug delivery system.

PMID- 19577802
TI  - The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and
      their suppression of cytotoxicity.
AB  - Among various hydrogels able to form monodisperse and stable nanoparticles (20-30
      nm) are those with pullulan-bearing cholesteryl moieties (CHP). These
      nanoparticles can interact with soluble proteins through hydrophobic bonding. The
      objectives of this study were to investigate whether CHP nanogels would interact
      with oligomeric forms of the 42 amino acid variant of beta-amyloid (Abeta(1-42))
      and if the formation of CHP-Abeta(1-42) oligomer entities will reduce
      cytotoxicity of Abeta(1-42) in primary cortical cells and microglial (N9) cells.
      By employing fluorescent CHP analogs with different charges we provide evidence
      that, (i) both neutral and positively charged CHP nanoparticles interact with
      Abeta(1-42) monomers and oligomers, (ii) neutral CHP is non-toxic, but positively
      charged derivatives (CHPNH2) are toxic, particularly in primary cortical
      cultures, and (iii) binding of both monomeric and oligomeric Abeta(1-42) to CHP
      significantly reduces Abeta(1-42) toxicity in both the primary cortical and
      microglial cells. These results suggest that CHP nanogels could provide a valid
      complementary approach to antibody immunotherapy in neurological disorders
      characterized by the formation of soluble toxic aggregates, such as those in
      Alzheimer's disease (AD).

PMID- 19577804
TI  - On the kinetics and impact of tetragonal to monoclinic transformation in an
      alumina/zirconia composite for arthroplasty applications.
AB  - Latest trends in load-bearing materials for arthroplastic applications involve
      the development of highly fracture resistant alumina/zirconia composites, as an
      alternative choice to alumina and zirconia monolithic ceramics. Composite
      materials are designed from both chemical and microstructural viewpoints in order
      to prevent environmental degradation and fracture events in vivo, whose shadow
      yet hampers the full exploitation of ceramic materials in the field of
      arthroplasty. The aim of this paper is to evaluate the resistance to
      environmental degradation in an alumina/zirconia composite (Biolox Delta), which
      represents a primary candidate for hip and knee joint applications. Our approach
      consists first in the experimental determination of an activation energy value
      for environmentally driven tetragonal to monoclinic (t-m, henceforth) polymorphic
      transformation in the zirconia phase of the material; then, based on such an
      experimental value, a prediction is given for the long-term in vivo environmental
      resistance of prostheses made of the composite material. The present evaluation
      clarifies the in vivo performance of this new composite for orthopedic
      applications.

PMID- 19577803
TI  - Bioengineered silk protein-based gene delivery systems.
AB  - Silk proteins self-assemble into mechanically robust material structures that are
      also biodegradable and non-cytotoxic, suggesting utility for gene delivery. Since
      silk proteins can also be tailored in terms of chemistry, molecular weight and
      other design features via genetic engineering, further control of this system for
      gene delivery can be considered. In the present study, silk-based block
      copolymers were bioengineered with poly(L-lysine) domains for gene delivery.
      Ionic complexes of these silk-polylysine based block copolymers with plasmid DNA
      (pDNA) were prepared for gene delivery to human embryonic kidney (HEK) cells. The
      material systems were characterized by agarose gel electrophoresis, atomic force
      microscopy, and dynamic light scattering. The polymers self-assembled in solution
      and complexed plasmid DNA through ionic interactions. The pDNA complexes with 30
      lysine residues prepared at a polymer/nucleotide ratio of 10 and with a solution
      diameter of 380 nm showed the highest efficiency for transfection. The pDNA
      complexes were also immobilized on silk films and demonstrated direct cell
      transfection from these surfaces. The results demonstrate the potential of
      bioengineered silk proteins as a new family of highly tailored gene delivery
      systems.

PMID- 19577805
TI  - Inhibition of mitochondrial calcium uptake rather than efflux impedes calcium
      release by inositol-1,4,5-trisphosphate-sensitive receptors.
AB  - Mitochondria modulate cellular Ca2+ signals by accumulating the ion via a
      uniporter and releasing it via Na+- or H+-exchange. In smooth muscle, inhibition
      of mitochondrial Ca2+ uptake inhibits Ca2+ release from the sarcoplasmic
      reticulum (SR) via inositol-1,4,5-trisphosphate-sensitive receptors (IP(3)R). At
      least two mechanisms may explain this effect. First, localised uptake of Ca2+ by
      mitochondria may prevent negative feedback by cytosolic Ca2+ on IP(3)R activity,
      or secondly localised provision of Ca2+ by mitochondrial efflux may maintain
      IP(3)R function or SR Ca2+ content. To distinguish between these possibilities
      the role of mitochondrial Ca2+ efflux on IP(3)R function was examined. IP(3) was
      liberated in freshly isolated single colonic smooth muscle cells and
      mitochondrial Na+-Ca2+ exchanger inhibited with CGP-37157 (10microM).
      Mitochondria accumulated Ca2+ during IP(3)-evoked [Ca2+](c) rises and released
      the ion back to the cytosol (within approximately 15s) when mitochondrial Ca2+
      efflux was active. When mitochondrial Ca2+ efflux was inhibited by CGP-37157, an
      extensive and sustained loading of mitochondria with Ca2+ occurred after IP(3)
      evoked Ca2+ release. IP(3)-evoked [Ca2+](c) rises were initially unaffected, then
      only slowly inhibited by CGP-37157. IP(3)R activity was required for inhibition
      to occur; incubation with CGP-37157 for the same duration without IP(3) release
      did not inhibit IP(3)R. CGP-37157 directly inhibited voltage-gated Ca2+ channel
      activity, however SR Ca2+ content was unaltered by the drug. Thus, the gradual
      decline of IP(3)R function that followed mitochondrial Na+-Ca2+ exchanger
      inhibition resulted from a gradual overload of mitochondria with Ca2+, leading to
      a reduced capacity for Ca2+ uptake. Localised uptake of Ca2+ by mitochondria,
      rather than mitochondrial Ca2+ efflux, appears critical for maintaining IP(3)R
      activity.

PMID- 19577806
TI  - The role of estrogenic compounds in the etiology of pediatric leukemia.

PMID- 19577807
TI  - Wild juvenile Dicentrarchus labrax L. liver antioxidant and damage responses at
      Aveiro Lagoon, Portugal.
AB  - The Aveiro Lagoon, at the north-western coast of Portugal, has been under
      considerable anthropogenic pressure for the last 5 decades. In order to perform
      an adequate survey of the effects induced by the contaminants in presence, wild
      juveniles Dicentrarchus labrax (sea bass) were selected. Thus, sea bass was
      captured at five sites: Torreira (TOR, as reference site), Gafanha (GAF), Rio
      Novo Principe (RIO), Laranjo (LAR) and Vagos (VAG) in autumn 2005. Liver defence
      responses such as catalase (CAT), glutathione peroxidase (GPx), glutathione
      reductase (GR), glutathione S-transferase (GST), total glutathione (GSHt), total
      non-protein thiols (NP-SH) and metallothioneins (MT) were measured. Liver damage
      was determined as lipid peroxidation (LPO) and DNA integrity loss. RIO, LAR and
      VAG presented lower CAT, GR, GST activities and NP-SH and GSHt depletion in
      comparison to TOR. VAG and LAR showed higher GPx activity when compared to TOR.
      The highest MT level was found at GAF and VAG. The NP-SH and DNA integrity
      decreased at GAF compared to TOR. This field study demonstrated that not only
      antioxidant induction but also inhibitory responses must be considered as a
      signal of contamination.

PMID- 19577808
TI  - Randomized comparison of ultra-brief bifrontal and unilateral electroconvulsive
      therapy for major depression: cognitive side-effects.
AB  - OBJECTIVE: The cognitive side-effects of bifrontal (BF) and right unilateral (UL)
      ultra-brief pulse (0.3 ms) electroconvulsive therapy (ECT) were compared, in the
      treatment of patients with a depressive episode. METHOD: Neuropsychological
      functioning in patients with a medication refractory depressive episode, that
      were treated with a course of BF ultra-brief ECT at 1.5 times seizure threshold
      (ST) or UL ultra-brief ECT at 6 times ST, by random assignment, was assessed
      before treatment, and 1 and 6 weeks after the treatment course, by a blinded
      rater. RESULTS: Of the 64 patients that were included, 32 (50%) received BF ECT,
      and 32 (50%) received UL ECT, by random assignment. Neuropsychological testing 1
      and 6 weeks after treatment was performed by 30 (93.75%) and 19 (59.37%)
      patients, respectively, in the BF-group and 29 (90.62%) and 20 (62.50%),
      respectively, in the UL-group. There was no deterioration in any of the
      neuropsychological measures. Patients rated their memory as clearly improved
      after treatment. There were no significant differences between the patients given
      BF ECT and those given UL ECT. CONCLUSIONS: Ultrabrief pulse ECT, used either in
      combination with a UL electrode position and a stimulus of 6 times ST, or a BF
      electrode position with a stimulus of 1.5 times ST, are effective antidepressant
      techniques, that do not have a deleterious effect on cognitive function.

PMID- 19577809
TI  - Chronic use of the immunomodulating tripeptide feG-COOH in experimental feline
      asthma.
AB  - We have previously documented that a single dose of feG-COOH prior to allergen
      challenge significantly decreased eosinophilic airway inflammation in cats with
      experimental asthma, but did not result in complete resolution of airway
      inflammation. This study was undertaken to determine if a chronic (2 weeks)
      course of feG-COOH in experimentally asthmatic cats would induce complete
      remission of airway inflammation and clinical signs of asthma. Experimental
      asthma was induced using Bermuda grass allergen (BGA) and cats were randomly
      selected to receive either feG-COOH (1mg/kg, PO) or saline for 2 weeks, followed
      by a 2-week washout period. Cats then received the alternate treatment. Aerosol
      challenge with BGA was performed weekly throughout the study and bronchoalveolar
      lavage fluid (BALF) and blood were collected prior to and after each of the 2
      week treatment periods. Regular use of feG-COOH had no significant effect on
      airway inflammation, BALF and plasma TNF bioactivity or a clinical sign compared
      to placebo. Regular use of feG-COOH can thus not be recommended as the sole
      therapy for feline allergic asthma.

PMID- 19577810
TI  - Systemic response to low-dose endotoxin infusion in cats.
AB  - Sepsis is a common problem in feline patients and is associated with substantial
      morbidity and mortality. There has been little research investigating the
      physiologic response to bacterial infection in cats, in part because appropriate
      models have not been developed. The objective of this study was to characterize
      the response to low-dose LPS infusion in conscious, healthy cats. Measures of
      systemic inflammation, hemodynamic stability, coagulation, metabolic function,
      and organ damage were compared between placebo and low-dose LPS infusion
      (2mcg/kg/hx4h, IV) in cats, with each cat serving as its own control. Markers of
      systemic inflammation including temperature, plasma TNF activity, IL-6, CXCL-8
      and IL-10 concentrations were significantly increased and white blood cell counts
      were significantly decreased after LPS infusion. A biphasic hypotensive response
      was observed after initiation of LPS infusion without concurrent tachycardia.
      Additionally, LPS administration significantly increased blood glucose, lactate
      and creatinine concentrations. Patchy alveolar congestion, multifocal acute
      alveolar epithelial necrosis, and mild pulmonary edema were noted in the lungs
      along with acute centrilobular hepatocellular necrosis, and mild lymphocyte
      apoptosis in the spleen and/or intestinal Peyer's patches. No biologically
      significant alterations in coagulation parameters developed after LPS infusion.
      Low-dose LPS infusion in cats induced systemic inflammation, hemodynamic
      derangement, metabolic alterations and mild organ damage. Low-dose endotoxin
      infusion is a viable pre-clinical model to study naturally developing sepsis in
      cats.

PMID- 19577812
TI  - Assessment of left ventricular diastolic events interrelations: an integrated
      approach.
AB  - BACKGROUND: Left ventricular (LV) diastolic function represents a complex
      performance that involves long axis displacement, myocardial lengthening
      velocities as well as cavity filling. The aim of this study was to assess the
      various diastolic event interrelations in a group of patients with different
      degrees of diastolic dysfunction. METHODS: 128 consecutive subjects with various
      degrees of diastolic impairment were studied by Doppler echocardiography. The
      amplitude of early diastolic (El) and late diastolic (Al) long axis lengthening
      was measured by M-mode and corresponding myocardial velocities (Ea and Aa) by
      Tissue Doppler. LV filling velocities were also acquired by spectral pulsed wave
      Doppler. RESULTS: Early diastolic long axis amplitudes and velocities correlated
      (r=0.73, P<0.0001) as did late diastolic ones (r=0.67, P<0.0001). El of <=5.6 mm
      was 80.6% sensitive and 70.5% specific in predicting Ea of <8.0 cm/s, a feature
      of LV impaired relaxation. El/Al correlated with Ea/Aa (r=0.78, P<0.0001), as did
      E/El with E/Ea ratios (r=0.74, P<0.0001). An E/El ratio>17.3 cm/s/mm had 94.1%
      sensitivity and 87.4% specificity for predicting an E/Ea ratio>15, a marker for
      raised LV filling pressures. El<=6.8 mm, total amplitude of diastolic motion
      (El+Al)<=11.5 mm, and E/El>14.2 cm/s/mm were the best criteria to discriminate
      between normal diastolic function and pseudonormal/restrictive LV filling.
      CONCLUSION: Diastolic LV components of motion, amplitude and velocities are not
      independent, neither from each other nor from filling pressures. An integrated
      approach towards using them all in assessing diastolic function, particularly in
      patients with raised filling pressure should be of great clinical value.

PMID- 19577813
TI  - Preliminary investigation of a humoral and cell-mediated immunity ratio for
      diagnosis of paratuberculosis in beef cattle.
AB  - One thousand three hundred and twenty-four adult beef cattle were tested for
      paratuberculosis using 2 antibody enzyme-linked immunosorbent assays (ELISA), an
      interferon-gamma (INF-gamma) ELISA, and radiometric bacterial culture of feces
      from 5 populations. Two populations of cattle (n=226) had data available to
      calculate a ratio of humoral to cell-mediated immunity based on results from one
      antibody test and the INF-gamma ELISA. Latent class analysis was used to estimate
      accuracy of the 4 paratuberculosis assays within a Bayesian framework.
      Determination of test accuracy and paratuberculosis prevalence in the latent
      class analysis allowed for estimation of predictive value positive (PVP)
      functions. The estimated PVP functions were used to iteratively assign
      paratuberculosis status to sampled cattle. Accuracy of the immunity ratio, an
      antibody ELISA, and the INF-gamma ELISA were determined for multiple cutoffs
      based on probabilistically assigned paratuberculosis status. Area under the
      receiver-operating characteristic (ROC) curves (95% probability interval) were
      estimated as 0.78 (0.66, 0.89), 0.81 (0.68, 0.92), and 0.59 (0.47, 0.71) for the
      immunity ratio, antibody ELISA, and INF-gamma ELISA, respectively. The Youden
      index (sensitivity+specificity-1) peaked at immunity ratios of 0.5 (J=0.48) and
      1.0 (J=0.46). Sensitivity and specificity (95% probability interval) at an
      immunity ratio cutoff of 0.5 were 0.65 (0.44, 0.85) and 0.83 (0.78, 0.88),
      respectively. Sensitivity and specificity (95% probability interval) at the 1.0
      cutoff were 0.55 (0.33, 0.77) and 0.91 (0.87, 0.95), respectively. An immunity
      ratio could be used to diagnosis paratuberculosis in beef cattle but requires
      further investigation.

PMID- 19577814
TI  - Potential of silica bodies (phytoliths) for nanotechnology.
AB  - Many plant systems accumulate silica in solid form, creating intracellular or
      extracellular silica bodies (phytoliths) that are essential for growth,
      mechanical strength, rigidity, predator and fungal defence, stiffness and
      cooling. Silica is an inorganic amorphous oxide formed by polymerization
      processes within plants. There has been much research to gain new insights into
      its biochemistry and to mimic biosilicification. We review the background on
      plant silica bodies, silica uptake mechanisms and applications, and suggest
      possible ways of producing plant silica bodies with new functions. Silica bodies
      offer complementary properties to diatoms for nanotechnology, including large
      scale availability from crop wastes, lack of organic impurities (in some),
      microencapsulation and microcrystalline quartz with possibly unique optical
      properties.

PMID- 19577811
TI  - Neuroprotective effects of the complement terminal pathway during demyelination:
      implications for oligodendrocyte survival.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system that is mediated by activated lymphocytes,
      macrophages/microglia, and complement. In MS, the myelin-forming oligodendrocytes
      (OLGs) are the targets of the immune attack. Experimental evidence indicates that
      C5b-9 plays a role in demyelination during the acute phase of experimental
      allergic encephalomyelitis (EAE). Terminal complement C5b-9 complexes are capable
      of protecting OLGs from apoptosis. During chronic EAE complement C5 promotes
      axonal preservation, remyelination and provides protection from gliosis. These
      findings indicate that the activation of complement and C5b-9 assembly can also
      have protective roles during demyelination.

PMID- 19577815
TI  - Main microorganisms involved in the fermentation of Ugandan ghee.
AB  - Ghee is widely produced from a traditional fermented butter-like product named
      mashita in western Uganda. However, no detailed studies have been done to
      identify the microorganisms involved in mashita fermentation. The aim of this
      study was to identify the microorganisms present at the end of mashita ripening
      using culture-dependent and culture-independent techniques. The most commonly
      identified species of lactic acid bacteria (LAB) in mashita using culture
      dependent techniques were Lactobacillus paracasei, Lactobacillus helveticus,
      Lactobacillus plantarum and Lactobacillus perolens constituting 37.3%, 10.1%,
      8.1% and 7.7% of total bacterial colonies isolated respectively. L. paracasei was
      the only bacterial species identified in all mashita samples by culture-dependent
      technique. Two of the four most commonly isolated LAB species (L. helveticus and
      L. plantarum) were also identified in mashita by a culture-independent method
      (PCR-DGGE). Other main LAB species identified in mashita by PCR-DGGE were
      Bifidobacterium sp., Enterococcus faecium, Lactobacillus brevis, Lactobacillus
      acetotolerans, Lactobacillus sp., Lactococcus raffinolactis, Lactococcus lactis
      subsp. lactis and Streptococcus salivarius. The main species of acetic acid
      bacteria (AAB) identified in the mashita using PCR-DGGE method were Acetobacter
      aceti, Acetobacter lovaniensis, Acetobacter orientalis and Acetobacter
      pasteurianus. PCR-DGGE identification of yeasts showed that Brettanomyces
      custersianus, Candida silvae, Geotrichum sp., Issatchenkia occidentalis,
      Issatchenkia orientalis, Kluyveromyces marxianus, Saccharomyces cerevisiae, and
      Trichosporon asahii were main yeast species in mashita. A. lovaniensis, A. aceti,
      and I. orientalis were identified in all the six mashita samples analyzed using
      PCR-DGGE method. Other microbial species were only found in some samples. These
      results indicate that LAB and yeasts, as in similar fermentation products, but
      also AAB are main microbial groups involved in mashita fermentation.

PMID- 19577816
TI  - Pemetrexed in the treatment of advanced non-squamous lung cancer.
AB  - Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase
      and other folate-dependent enzymes. Firstly, pemetrexed was approved in
      combination with cisplatin for the treatment of malignant pleural mesothelioma.
      Successively, it has been studied, as single-agent, in phase II and III trials
      for second-line therapy of non-small cell lung cancer (NSCLC). Based on these
      results, pemetrexed has been registered for the treatment of recurrent NSCLC. The
      next step was to test pemetrexed plus cisplatin versus gemcitabine plus
      cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non
      inferiority, randomized trial. This trial reported the pemetrexed plus cisplatin
      regimen to be not inferior, in terms of activity and efficacy, to the control arm
      but statistically better tolerated. The role of pemetrexed as maintenance therapy
      after first-line therapy for advanced NSCLC is currently being evaluated into a
      phase III trial. The consistency of the results of these recent studies has
      identified a predictive effect of NSCLC non-squamous histology for pemetrexed. To
      date, pemetrexed is registered, at the dose of 500 mg/m(2) on day 1 of a 3-week
      schedule, in combination with cisplatin, for first-line therapy and, as single
      agent, for second-line treatment of patients with non-squamous NSCLC.This review
      shows the latest and indicates the future developments of pemetrexed in the
      treatment of advanced NSCLC patients.

PMID- 19577817
TI  - Invasive species, ecosystem services and human well-being.
AB  - Although the effects of invasive alien species (IAS) on native species are well
      documented, the many ways in which such species impact ecosystem services are
      still emerging. Here we assess the costs and benefits of IAS for provisioning,
      regulating and cultural services, and illustrate the synergies and tradeoffs
      associated with these impacts using case studies that include South Africa, the
      Great Lakes and Hawaii. We identify services and interactions that are the least
      understood and propose a research and policy framework for filling the remaining
      knowledge gaps. Drawing on ecology and economics to incorporate the impacts of
      IAS on ecosystem services into decision making is key to restoring and sustaining
      those life-support services that nature provides and all organisms depend upon.

PMID- 19577818
TI  - Role of ovarian hormones in age-associated thymic involution revisited.
AB  - A commonly held view that ovarian hormones are causally involved in age
      associated thymic involution has been recently challenged. In particular, their
      relevance in the progression of thymic involution has been disputed. To reassess
      this issue 10-month-old rats with well advanced thymic involutive changes were
      ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development
      and levels of recent thymic emigrants (RTEs) were examined in peripheral blood
      and spleen. In addition, the distribution of major conventional and regulatory T
      cell subsets was analyzed in the same peripheral lymphocyte compartments.
      Ovariectomy increased thymic weight and cellularity above the levels in both 10
      month-old and age-matched controls indicating that ovarian hormone ablation not
      only prevented further progression of thymic involution, but also reversed it.
      The increased thymic cellularity was accompanied by altered thymocyte
      differentiation/maturation culminating in increased thymic output of naive T
      cells as indicated by elevated levels of both CD4+ and CD8+ RTEs in peripheral
      blood and spleen. The changes in T-cell development produced: (i) a
      disproportional increase in cellularity across thymocyte subsets, so that
      relative proportions of cells at all maturational stages preceding the CD4+CD8+ T
      cell receptor (TCR)alphabeta(low) stage were reduced; the relative numbers of
      CD4+CD8+ TCRalphabeta(low) cells entering positive selection and their immediate
      CD4+CD8+ TCRalphabeta(high) descendents were increased, while those of the most
      mature CD4+CD8- and CD4-CD8+ TCRalphabeta(high) cells remained unaltered; (ii)
      enhanced cell proliferation across all thymocyte subsets and (iii) reduced
      apoptosis of cells within the CD4+CD8+ thymocyte subset. The augmented thymic
      output of naive T cells in Ovx rats most likely reflected an early disinhibition
      of thymocyte development followed by increased positive/reduced negative
      selection, at least partly, due to raised thymocyte surface Thy-1 expression. The
      greater number of CD4+CD25+Foxp3+ cells in both thymus and peripheral blood
      suggested augmented thymic production of these cells. In addition, an increased
      CD4+/CD8+ cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone
      ablation led not only to increased diversity of the T-cell repertoire, but also
      to a new balance among distinct T-cell subsets in the periphery.

PMID- 19577819
TI  - Engagement of BDCA-2 blocks TRAIL-mediated cytotoxic activity of plasmacytoid
      dendritic cells.
AB  - Plasmacytoid dendritic cells (PDC) are a functionally distinct lineage of
      dendritic cells characterized by the release of large amounts of type I
      interferon (IFN I). IFN I release is efficiently triggered by viral infection and
      modulates several aspects of immune reactions including the activation of
      cytotoxic mechanisms finalized to the elimination of infected cells. In this
      study, we report that TLR7 and TLR9 ligands can induce the secretion of
      biologically active TNF-related apoptosis-inducing ligand (TRAIL) by PDC.
      Accordingly, PDC supernatant is endowed with TRAIL-mediated cytotoxic activity
      when tested on a TRAIL-sensitive Jurkat cell line. TRAIL production is only
      partially dependent on the autocrine production of IFN I as documented by the use
      of a blocking anti-IFNRA antibody and the stimulation with exogenous IFN I.
      Importantly, both TRAIL secretion and cytotoxic activity of PDC supernatants are
      completely abolished by BDCA2 ligation. These results provide further insights
      into the biological role of BDCA-2 and document a negative regulatory pathway of
      PDC cytotoxic activity that may be relevant in pathological situations such as
      tumors and autoimmune diseases.

PMID- 19577820
TI  - The psychiatric profile of patients with psychogenic excoriation.
AB  - BACKGROUND: Psychogenic excoriation describes patients who excoriate without
      apparent primary skin abnormality. OBJECTIVE: This study compares the psychiatric
      profile of patients with psychogenic excoriation with a control group. METHODS:
      Fifty consecutive patients with psychogenic excoriation were matched with 50
      control patients and given a questionnaire related to psychiatric history.
      RESULTS: Study and control groups differed significantly in relation to
      psychiatric comorbidity, use of psychotropic drugs, history of depression, and
      history of bipolar disorder. Psychogenic excoriation was not associated with
      personal history of other psychiatric disorders or family history of psychiatric
      comorbidity, except alcoholism. LIMITATIONS: Nonpsychiatrists may have made the
      psychiatric diagnoses. CONCLUSION: Psychogenic excoriation is significantly
      associated with psychiatric comorbidity, especially depression and bipolar
      disorder. Awareness by the patient of a link between the psychiatric disorder and
      the cutaneous condition may help patients in dealing with the distress caused by
      the unknown nature of the excoriating behavior.

PMID- 19577821
TI  - Reduced levels of human apoE4 protein in an animal model of cognitive impairment.
AB  - The APOE4 allele is the most common genetic determinant for Alzheimer's disease
      (AD) in the developed world. APOE genotype specific differences in brain
      apolipoprotein E protein levels have been observed in numerous studies since the
      discovery of APOE4's link to AD. Since the human apoE4 targeted replacement mice
      display characteristics of cognitive impairment we sought to determine if reduced
      levels of apoE might provide one explanation for this impairment. We developed a
      novel mass spectrometry method to measure apoE protein levels in plasma.
      Additionally, we developed an ELISA that replicates the mass spectrometry data
      and enables the rapid quantitation of apoE in plasma, brain and cerebrospinal
      fluid. We detected a significant decrease in plasma, brain and cerebrospinal
      fluid apoE levels in the apoE4 mice compared to apoE2 and E3 mice. We also
      measured a small (~19%) decrease in brain apoE levels from aged, non-demented
      APOE4 carriers. Our findings suggest that a fraction of APOE4-linked AD may be
      due to insufficient levels of functional apoE required to maintain neuronal
      health.

PMID- 19577822
TI  - [The future of geriatrics].

PMID- 19577823
TI  - [Commentary: Integrating dimensions in the intervention with older adults].

PMID- 19577824
TI  - Synthesis, crystal structure, DNA interaction and antioxidant activities of two
      novel water-soluble Cu2+ complexes derivated from 2-oxo-quinoline-3-carbaldehyde
      Schiff-bases.
AB  - Two novel 2-oxo-quinoline-3-carbaldehyde (4'-hydroxybenzoyl) hydrazone,
      thiosemicarbazone ligands and its corresponding Cu(2+) complexes were
      synthesized, and the two complexes' structures were determined by X-ray single
      crystal diffraction. The interaction of the two Cu(2+) complexes with calf thymus
      DNA (CT-DNA) was investigated by electronic absorption spectroscopy, fluorescence
      spectroscopy and viscosity measurement. The experimental evidences indicated that
      the two water-soluble Cu(2+) complexes could strongly bind to CT-DNA via an
      intercalation mechanism. The intrinsic binding constants of complexes 1 and 2
      with CT-DNA were 7.31 x 10(6) and 2.33 x 10(6)M(-1), respectively. Furthermore,
      the antioxidant activities (hydroxyl radical and superoxide) of the two water
      soluble metal complexes were determined by hydroxyl radical and superoxide
      scavenging method in vitro.

PMID- 19577825
TI  - Synthesis, crystal structures and antibacterial activity studies of aza
      derivatives of phytoalexin from cotton plant--gossypol.
AB  - Using Gossypol (GOS) extracted from cotton seeds, a series of its Schiff bases (1
      18) and hydrazones (19-27) have been synthesized and evaluated for their
      antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria
      and yeast-like organisms. Of the 27 aza-derivatives of gossypol, 11 have been
      found active against the microorganisms tested, similar to gossypol. Crystal
      structures of the new Schiff base (compound 7) and hydrazone (compound 25) of
      gossypol reveal the presence of two different tautomers within two types of the
      aza-derivatives studied. The newly synthesized aza-derivatives of gossypol are
      characterized by the FT-IR, NMR and MS methods.

PMID- 19577826
TI  - [Increase of CXCL10 serum level in systemic sclerosis interstitial pneumonia].
AB  - INTRODUCTION: CXCL10, a gamma-interferon-induced chemokine seems to play a
      relevant role in lung involvement that occurs in systemic sclerosis (SSc). The
      objective of this study was to assess the serum level of CXCL10 in interstitial
      lung disease (ILD) associated with SSc. METHODS: Serum level of CXCL10 was
      assayed in 23 healthy volunteers (60.0 years; 58.0-67.3) and 29 SSc patients
      (63.1 years; 60.1-69.4) by ELISA method. Pulmonary function tests (PFTs), lung CT
      scan and echocardiogram were also performed in the patients. Serum levels from
      patients and healthy controls were compared and a comparison among SSc patients
      between those with and without ILD, as documented by lung CT-scan, was also
      performed. RESULTS: Median CXCL10 level from patients with SSc was significantly
      higher than that from healthy volunteers (110.0 pg/ml; 60.8-223.8 versus 52.0;
      41.3-65.8; p<0.001). Fifteen out of the 29 patients had ILD on lung CT-scan; the
      median CXCL10 level from SSc patients with ILD was significantly higher than that
      from SSc patients without ILD (210.0 pg/ml; 115.0-307.5 versus 76.0; 55.0-110.0;
      p=0.02). CONCLUSION: Our findings suggest that CXCL10 is specifically increased
      in the lung involvement of SSc and plays a role in scleroderma lung disease.

PMID- 19577827
TI  - Head and neck chondrosarcoma: analysis of 16 cases.
AB  - OBJECTIVE: Head and neck chondrosarcomas are rare, accounting for less than 12%
      of all chondrosarcomas. Few studies with larger series approach the
      clinicopathological characteristics of these tumours. The aim of this study was
      describe clinical findings, management and outcome of 16 cases of head and neck
      chondrosarcoma from a single institution. STUDY DESIGN: The files of the Cancer
      Hospital A.C. Camargo were reviewed, and data from patients with head and neck
      chondrosarcoma were collected. RESULTS: Mean age was 36 years, with slight male
      predilection. The most common site affected was maxilla (43%). Surgery was the
      main modality treatment performed in 10 patients. Overall 5-year survival rate
      was 56.4%. Although it was not statistically significant, the most important
      factor affecting overall survival was tumour size. CONCLUSION: Early diagnosis
      and adequate surgical resection are important to get better survival rates.

PMID- 19577828
TI  - Accuracy of maxillary positioning in bimaxillary surgery.
AB  - The aim of the study was to investigate the accuracy of a modified pin system for
      the vertical control of maxillary repositioning in bimaxillary osteotomies. The
      preoperative cephalograms of 239 consecutive patients who were to have
      bimaxillary osteotomies were superimposed on the postoperative films. Planned and
      observed vertical and horizontal movements of the upper incisor were analysed
      statistically. The mean deviations of -0.07 mm (95% confidence intervals (CIs) 
      0.17 to 0.04 mm) for the vertical movement and 0.12 mm (95% CI -0.06 to 0.30 mm)
      for the horizontal movement did not differ significantly from zero. Comparison of
      the two variances between intrusion and extrusion of the maxilla did not differ
      significantly either (p=0.51). These results suggest that the modified pin system
      for vertical control combined with interocclusal splints provides accurate
      vertical positioning of the anterior maxilla in orthognathic surgery.

PMID- 19577829
TI  - Randomised controlled trial of the effectiveness of using foot reflexology to
      improve quality of sleep amongst Taiwanese postpartum women.
AB  - OBJECTIVE: to examine the effectiveness of using foot reflexology to improve
      sleep quality in postpartum women. DESIGN AND SETTING: randomised controlled
      trial, conducted at two postpartum centres in northern Taiwan. PARTICIPANTS: 65
      postpartum women reporting poor quality of sleep were recruited from July 2007 to
      December 2007. INTERVENTIONS: participants were assigned randomly to either an
      intervention or a control group. Participants in both groups received the same
      care except for reflexology therapy. The intervention group received a single 30
      minute foot reflexology session at the same time each evening for five
      consecutive days. Sessions were administered by a certified nurse reflexologist.
      MEASURES AND FINDINGS: the outcome measure was the Pittsburgh sleep quality index
      (PSQI), and this was performed at baseline and post test. Mean PQSI scores for
      both groups declined over time between baseline and post test. Using a
      generalised estimation equation to control several confounding variables, the
      changes in mean PSQI were found to be significantly lower in the intervention
      group (beta=-2.24, standard error=0.38, p<0.001) than in the control group.
      CONCLUSION: an intervention involving foot reflexology in the postnatal period
      significantly improved the quality of sleep. IMPLICATIONS FOR PRACTICE: midwives
      should evaluate maternal sleep quality and design early intervention programmes
      to improve quality of sleep in order to increase maternal biopsychosocial well
      being. Midwives interested in complementary therapies should be encouraged to
      obtain training in reflexology and to apply it in clinical settings if it is
      allowed.

PMID- 19577830
TI  - Dissecting the spatial scales of mercury accumulation in Ontario lake sediment.
AB  - Total mercury concentration was analyzed in 171 lakes from pre-industrial (>30 cm
      depth; Hg(pre-industrial)) and present-day sediments (0.5-1 cm; Hg(present-day)).
      Numerous hot or cold spots of sediment mercury enrichment (Hg EF; Hg(pre
      industrial)/Hg(present-day)) were evident as determined by local tests of
      autocorrelation, although in most cases, the maximum correlation among sites was
      not the nearest neighbor, indicating a strong influence of watershed
      characteristics. Hg EF was correlated with the area of open water (ha) (r = 0.91,
      p = 0.035), mine tailings (r = 0.94, p = 0.019), and organic deposits in
      surficial geology of the watershed (r = -0.91, p = 0.034). Through use of local
      rather than global regression coefficients, R(2) increased from 0.20 (p = 0.005)
      to 0.60 (p = 0.013). A broad spatial pattern (>500 km) observed only in Hg(pre
      industrial) was best explained by mean annual precipitation (shared variance =
      3.5%), while finer spatial patterns only observed in Hg(present-day) and Hg EF
      were best explained by pH (average shared variance = 10.8%).

PMID- 19577831
TI  - Clinical and laboratory assessment of the subjective experience of drug craving.
AB  - Measures of subjective drug craving - often defined as the experience of an
      intense or compelling urge or desire - may be used to predict relapse, evaluate
      psychological and pharmacological treatments, and test theories of addiction and
      craving. This review summarizes both direct self-report questionnaires and
      indirect behavioral, physiological and reaction time measures designed to assess
      craving for alcohol, amphetamines, cocaine, heroin, marijuana, and tobacco. Multi
      item questionnaires have typically been based on one of four underlying
      conceptualizations of addiction or craving (obsessive-compulsive, approach
      avoidance, multi-dimensional, intensity-frequency-duration). Most multi-item self
      report questionnaires have high internal consistency, correlate significantly
      with single-item craving ratings, and demonstrate several aspects of construct
      validity. Proposed indirect or proxy measures of craving include drug dreams,
      speed of drug consumption, willingness to work for drug access, selection of
      monetary rewards over drug access, psychophysiological reactivity, and
      attentional bias to drug cues. These proxy measures of craving are presumed to
      obviate self-report biases, to be less subject to conscious self-control, and to
      reflect craving which the person may not be able to articulate; however, there
      have been too few demonstrations of their validity and they have too many
      practical limitations to supplant self-report measures of craving at this time.

PMID- 19577832
TI  - Women, mothers and HIV care in resource-poor settings.

PMID- 19577833
TI  - The reproductive needs and rights of people living with HIV in Argentina: health
      service users' and providers' perspectives.
AB  - This article focuses on the contraceptive and reproductive experiences and needs
      of people living with HIV and on public health services' responses to them in
      Argentina. Data collected through a national survey amongst people living with
      HIV (N=841) and semi-structured interviews (N=89) explored the perspectives of
      both health-care users and HIV/AIDS program coordinators and providers. The
      survey revealed that 55% of women and 30% of men had had children after their HIV
      diagnosis and that half of those pregnancies had been unintended. At the time of
      the survey in 2006, 73% of men and 64% of women did not want a (new) pregnancy.
      The vast majority report systematic condom use, but acknowledge difficulties
      complying with this recommendation. Dual protection (i.e., condom use plus
      another method) is low among those who do not want children or another pregnancy
      (8% of women and 9% of men reported using it). Mostly women and heterosexual men
      without children either expressed their wish or were seeking to be parents.
      Institutional and cultural barriers to friendly and/or effective contraceptive
      and reproductive counselling were identified. Most physicians encourage only
      condom use while a minority refers patients to family planning providers or talk
      with them about contraception. A lack of updated information about interactions
      between antiretroviral drugs and hormonal contraception and/or intrauterine
      devices was not infrequent among providers. Users reported having being
      discouraged or blamed by health professionals when they revealed they wanted to
      have (or were expecting) a baby. Professionals and program directors' attitudes
      regarding reproduction range from not acknowledging people's wishes, to providing
      useful information or referral. Whether wanted or unexpected, parenthood is a
      challenge for many of the people living with HIV. Social and biomedical responses
      still need to be refined in order to fully respect people's rights and succeed in
      preventing (re)infection as well as unwanted pregnancies. Drawing on study
      results, recommendations to enhance the provision of adequate information and
      services to help people prevent unwanted pregnancies or reproduce as safely as
      possible are discussed.

PMID- 19577834
TI  - Illness careers and continuity of care in mental health services: a qualitative
      study of service users and carers.
AB  - Continuity of care is considered by patients and clinicians as an essential
      feature of good quality care in long-term disorders, yet there is general
      agreement that it is a complex concept and the lack of clarity in its
      conceptualisation and operationalisation has been linked to a deficit of user
      involvement. In this paper we utilise the concept of the 'patient career' to
      frame patient accounts of their experiences of the mental health care system. We
      aimed to capture the experiences and views of users and carers focusing on the
      meanings associated with particular (dis)continuities and transitional episodes
      that occurred over their illness career. As part of a large longitudinal study of
      continuity of care in mental health a sub-sample of 31 users was selected
      together with 14 of their carers. Qualitative interviews framed around the
      service user's illness career explored general experiences of relationship with
      services, care, continuity and transition from both user and carer perspectives.
      Five key themes emerged: relational (dis)continuity; depersonalised transitions;
      invisibility and crisis; communicative gaps and social vulnerability. One of the
      important findings was the fragility of continuity and its relationship to levels
      of satisfaction. Supportive, long-term relationships could be quickly undermined
      by a range of factors and satisfaction levels were often closely related to
      moments of transition where these relationships were vulnerable. Examples of
      continuity and well managed transitions highlighted the importance of
      professionals personalising transitions and situating them in the context of the
      daily life of service users. Further research is required to identify how best to
      negotiate these key points of transition in the future.

PMID- 19577835
TI  - Interplay between fluoride and abrasivity of dentifrices on dental erosion
      abrasion.
AB  - OBJECTIVES: Eroded teeth are more susceptible to toothbrushing wear than sound
      teeth. We tested the hypothesis that fluoride and abrasivity of dentifrices can
      interact, modulating the development of erosive-abrasive lesions. METHODS: Human
      enamel and root dentin specimens were submitted to cycles of demineralization,
      remineralization and toothbrushing using six dentifrices formulated with three
      different abrasivity levels: low (L), medium (M) and high (H); with (+F) and
      without (-F) fluoride. Surface loss was quantified by optical profilometry and
      compared among groups (alpha=0.05). RESULTS: In dentin, it was ranked: L<M<H, for
      both +F and -F dentifrices. In enamel, +F dentifrices had similar results;
      however for -F formulations, M and H did not differ. Fluoride reduced surface
      loss in enamel, at all abrasive levels. In dentin, the same fluoride effect was
      observed but only for the low abrasive formulation. CONCLUSIONS: Both fluoride
      and abrasivity were important modulators of enamel surface loss, while abrasivity
      had a higher impact than fluoride on dentin.

PMID- 19577836
TI  - Preterm birth and low birth weight among in vitro fertilization singletons: a
      systematic review and meta-analyses.
AB  - Our objective was to determine the risks of preterm birth (PTB) and low birth
      weight (LBW) in singletons conceived through in vitro fertilization (IVF)+/
      intracytoplasmic sperm injection (ICSI) compared to spontaneously conceived
      singletons after matching or controlling for at least maternal age. The MOOSE
      guidelines for meta-analysis of observational studies were followed. Medline and
      Embase were searched using comprehensive search strategies. Bibliographies of
      identified articles were reviewed. English language studies examining LBW or PTB
      in singletons conceived by IVF or IVF/intracytoplasmic sperm injection, compared
      with spontaneously conceived singletons, that matched or controlled for at least
      maternal age. Two reviewers independently assessed titles, abstracts, full
      articles and study quality and extracted data. Dichotomous data were meta
      analyzed using relative risks (RR) as measures of effect size with a random
      effects model and for continuous data weighted mean difference was calculated.
      Seventeen studies were included with 31,032 singletons conceived through IVF (+/
      ICSI) and 81,119 spontaneously conceived singletons. After matching or
      controlling for maternal age and often other factors, compared to spontaneously
      conceived singletons, IVF singletons had increased risks of our two primary
      outcomes, PTB (RR 1.84, 95% CI 1.54, 2.21) and LBW (<2500 g, RR 1.60, 95% CI
      1.29, 1.98). Singletons conceived through IVF or IVF/ICSI were at increased risk
      for late PTB (32-36 weeks, RR 1.52, 95% CI 1.01, 2.30), moderate PTB <32-33 weeks
      (RR 2.27, 95% CI 1.73, 2.97), very LBW (<1500 g, RR 2.65, 95% CI 1.83, 3.84), and
      intrauterine growth restriction (RR 1.45, 95% CI 1.04, 2.00), lower birth weights
      (-97 g, 95% CI -161 g, -33 g) and shorter mean gestations (-0.6 weeks, 95% CI 
      0.9 weeks, -0.4 weeks). In conclusion, IVF singletons have significantly
      increased risks of PTB, LBW and other adverse perinatal outcomes compared to
      spontaneously conceived singletons after matching or controlling for maternal age
      at least.

PMID- 19577837
TI  - Photo degradation of methyl orange by attapulgite-SnO2-TiO2 nanocomposites.
AB  - Photocatalytic removal of methyl orange under ultraviolet radiation has been
      studied using attapulgite (ATT) composites, which were synthesized by depositing
      SnO(2)-TiO(2) hybrid oxides on the surface of ATT to form a composite
      photocatalyst (denoted ATT-SnO(2)-TiO(2)) using an in situ sol-gel technique.
      Results showed that SnO(2)-TiO(2) nanocomposite particles with average size of
      about 10nm were loaded successfully on to the surface of ATT fibers and were
      widely dispersed. Correspondingly, the photocatalytic activity of ATT was
      improved significantly by loading SnO(2)-TiO(2). The photoactivity of the
      composite photocatalyst decreased in the sequence ATT-SnO(2)-TiO(2)>ATT
      SnO(2)>ATT-TiO(2)>ATT. In order to achieve the best photocatalyst, the molar
      ratio of SnO(2) and TiO(2) in the ATT-SnO(2)-TiO(2) composites was adjusted to
      give a series with proportions r=n(Ti)/(n(Ti)+n(Sn))=0.0, 0.25, 0.33, 0.50, 0.67,
      0.75, 0.80, 0.82, 0.86, 1.0. Results indicated that the proportion of SnO(2) and
      TiO(2) had a critical effect on the photocatalytic activity, which increased as
      the content of TiO(2) increased to r<or=0.82 and decreased when r>0.82. The
      highest degradation rate of methyl orange was 99% within 30 min obtained by using
      ATT-SnO(2)-TiO(2) with r=0.82. The repeated use of the composite photocatalyst
      was also confirmed.

PMID- 19577838
TI  - Capturing 1,3-butadiene by the highly ordered Al-containing SBA-15.
AB  - This investigation examined the instantaneous adsorption of 1,3-butadiene by
      aluminum-modified mesoporous silica SBA-15 at ambient temperature. To efficiently
      trap the 1,3-butadiene pollutant in environment, alumina was incorporated in SBA
      15 through various pathways such as one-pot synthesis, solid state grinding and
      impregnation, and the property-function relation of resulting composites were
      characterized with XRD, N(2) adsorption-desorption, FTIR and NH(3)-TPD
      techniques. Adsorption of N-nitrosopyrrolidine (NPYR) was employed for the first
      time to reveal the difference between the mesoporous silica with the same Al
      content but prepared with different methods, providing a potential method for the
      delicate characterization. Modification with alumina significantly increased the
      capability of SBA-15 to adsorb 1,3-butadiene, and the one-pot synthesized sample
      exhibited a higher activity than the post-modified samples, resulting from the
      formation of Bronsted acidic sites and reservation of silianol groups on SBA-15
      host.

PMID- 19577839
TI  - A comparison of arsenic tolerance, uptake and accumulation between arsenic
      hyperaccumulator, Pteris vittata L. and non-accumulator, P. semipinnata L.--a
      hydroponic study.
AB  - The differences in arsenic (As) tolerance, uptake and accumulation between Pteris
      vittata (an As hyperaccumulator) and P. semipinnata (nonaccumulator) were
      investigated under hydroponic conditions. The results showed that As uptake by P.
      vittata was significantly higher (p<0.05) than that of P. semipinnata.
      Significantly higher concentrations of As accumulated in the fronds of P.
      vittata, while in the roots of P. semipinnata. The short-term (<24h) uptake
      kinetics were fitted a hyperbolic equation which could be divided into linear and
      saturable components (described by Michaelis-Menten kinetics/model). The increase
      in hydrogen peroxide (H(2)O(2)) content in both plant species significantly
      correlated (p<0.05) with increasing As content in the plants and As exposure
      time, especially for midrib of P. semipinnata. P. semipinnata showed higher
      concentrations of H(2)O(2) than those of P. vittata. The relative electrical
      conductivity (REC, %) values in the root and pinnae followed a similar trend as
      plant H(2)O(2) contents, increasing with As exposure, especially for P.
      semipinnata. Significantly higher REC (%) values (p<0.05) were observed in the
      root than that in pinnae of P. semipinnata. The results indicated that high doses
      of As produced oxidative damages in both plant species.

PMID- 19577840
TI  - Extraction behavior of As, Pb, and Zn from mine tailings with acid and base
      solutions.
AB  - The aim of this study was to investigate the extraction behavior of As, Pb, and
      Zn from mine tailings for considering the feasibility of soil washing. Extraction
      of metals was studied for different extractant doses, solid/liquid ratios, and
      equilibrium times. Generally, high extraction efficiency was achieved with HCl,
      H(3)PO(4), and H(2)SO(4), while H(2)SO(4) proved to be problematic with respect
      to Pb. NaOH was found to be favorable in removing As, while it was not effective
      at extracting Pb and Zn. With optimum conditions, which were a 1:5 solid-liquid
      ratio and 2h of extraction time, 0.5M of HCl extracted 21.1-72.5%, 9.9-86.5%, and
      6.1-74.1% of As, Pb, and Zn, respectively. The power and Elovich function were
      adequate to describe adsorption kinetics. These results suggest that HCl and NaOH
      could be used to effectively extract all metals without selectivity and As with
      selectivity, respectively, in mine tailings and could be used for the design of
      soil washing process.

PMID- 19577841
TI  - Arsenic accumulation in Scutellaria baicalensis Georgi and its effects on plant
      growth and pharmaceutical components.
AB  - Scutellaria baicalensis Georgi is a traditional Chinese medicinal plant. The
      effects of arsenic (As) on the growth and the formation of pharmaceutical
      components of S. baicalensis, and the uptake and accumulation of As by S.
      baicalensis were investigated using a field pot-culture experiment. The results
      show that spiking low concentrations of As (</=100mgkg(-1)) into soils can hasten
      the growth and development of the roots. High levels of As, however, reduced
      plant growth. The concentrations of five flavone components were not
      significantly affected by spiking low concentrations of As (</=200mgkg(-1)) into
      soils. High levels of As inhibited the generation of baicalin and wogoninside,
      but facilitated the generation of baicalein, wogonin and oroxylin A in S.
      baicalensis Georgi. The concentration of As in each part of the plant was
      proportional to the concentration of As spiked into the soil. The application of
      phosphorus (P) to the soil promoted the uptake and accumulation of As in the
      roots of the plant, but this synergistic effect became weaker with the
      incremental addition of P. Dry biomass did not change in response to low levels
      of P addition (</=200mgkg(-1)) to soils, but it increased significantly under
      high levels of P. Based on the results of both this pot-culture experiment and
      human health risk assessments, maximum safety limits of 2.0mgkg(-1) of As in the
      roots of S. baicalensis Georgi and 70mgkg(-1) of As in cultivated soils are
      suggested.

PMID- 19577842
TI  - Biological decolorization of the reactive dyes Reactive Black 5 by a novel
      isolated bacterial strain Enterobacter sp. EC3.
AB  - Studies were carried out on the decolorization of the reactive dye Reactive Black
      5 by a newly isolated bacterium, EC3. Phenotypic characterization and
      phylogenetic analysis based on 16S rDNA sequence comparisons indicate that this
      strain belonged to the genus Enterobacter. The optimal conditions for the
      decolorizing activity of Enterobacter sp. EC3 were anaerobic conditions with
      glucose supplementation, at pH 7.0, and 37 degrees C. The maximum decolorization
      efficiency against Reactive Black 5 achieved in this study was 92.56%. Ultra
      violet and visible (UV-vis) analyses before and after decolorization and the
      colorless bacterial biomass after decolorization suggested that decolorization
      was due to biodegradation, rather than inactive surface adsorption. The bacterial
      strain also showed a strong ability to decolorize various reactive textile dyes,
      including both azo and anthraquinone dyes. To our knowledge, it is the first time
      that a bacterial strain of Enterobacter sp. has been reported with decolorizing
      ability against both azo and anthraquinone dyes.

PMID- 19577843
TI  - Photoelectrocatalytic degradation of tetracycline by highly effective TiO2
      nanopore arrays electrode.
AB  - The widely utilization of pharmaceutical and personal care products (PPCPs) in
      the pharmaceutical therapies and agricultural husbandry has led to the worldwide
      pollution in the environment. In this study, the photoelectrocatalytic (PEC)
      behaviors of typical PPCPs, tetracycline (TC), were performed via a highly
      effective TiO(2) nanopore arrays (TNPs) electrode, comparing with electrochemical
      (EC) and photocatalytic (PC) process. A significant photoelectrochemical
      synergetic effect in TC degradation was observed on the TNPs electrode and the
      rate constant for the PEC process of TNPs electrode was approximately 6.7 times
      as high as its PC process. The TC removal rate achieved approximately 80% within
      3h PEC reaction by TNPs electrode, which is approximately 25% higher than that
      obtained for a conventional coated TiO(2) nanofilm electrode fabricated by sol
      gel method. The possible mechanism involved in the PEC degradation of TC by TNPs
      electrode was discussed. Furthermore, the TNPs electrode also shows enhanced
      photocurrent response compared with that for the coated TiO(2) nanofilm
      electrode. Such kind of TiO(2) nanopores will have many potential applications in
      various areas as an outstanding photoelectrochemical material.

PMID- 19577844
TI  - Response surface modeling of Pb(II) removal from aqueous solution by Pistacia
      vera L.: Box-Behnken experimental design.
AB  - A three factor, three-level Box-Behnken experimental design combining with
      response surface modeling (RSM) and quadratic programming (QP) was employed for
      maximizing Pb(II) removal from aqueous solution by Antep pistachio (Pistacia vera
      L.) shells based on 17 different experimental data obtained in a lab-scale batch
      study. Three independent variables (initial pH of solution (pH(0)) ranging from
      2.0 to 5.5, initial concentration of Pb(II) ions (C(0)) ranging from 5 to 50 ppm,
      and contact time (t(C)) ranging from 5 to 120 min) were consecutively coded as
      x(1), x(2) and x(3) at three levels (-1, 0 and 1), and a second-order polynomial
      regression equation was then derived to predict responses. The significance of
      independent variables and their interactions were tested by means of the analysis
      of variance (ANOVA) with 95% confidence limits (alpha=0.05). The standardized
      effects of the independent variables and their interactions on the dependent
      variable were also investigated by preparing a Pareto chart. The optimum values
      of the selected variables were obtained by solving the quadratic regression
      model, as well as by analysing the response surface contour plots. The optimum
      coded values of three test variables were computed as x(1)=0.125, x(2)=0.707, and
      x(3)=0.107 by using a LOQO/AMPL optimization algorithm. The experimental
      conditions at this global point were determined to be pH(0)=3.97, C(0)=43.4 ppm,
      and t(C)=68.7 min, and the corresponding Pb(II) removal efficiency was found to
      be about 100%.

PMID- 19577845
TI  - Charge compensation by in-situ heating for insulating ceramics in scanning
      electron microscope.
AB  - With a steady temperature increase under high vacuum (HV) in an environmental
      scanning electronic microscope, we observed charge-free characterization and fine
      secondary electron (SE) images in focus for insulating ceramics (alumina (Al2O3),
      aluminum nitride (AlN), pure magnesium silicate (Mg2SiO4)). The sample current
      I(sc) increased from -8.18 x 10(-13) to 2.76 x 10(-7)A for Al2O3 and -9.28 x 10(
      12) to 2.77 x 10(-6)A for AlN with the temperature increased from 298 to 633K.
      The surface conductance sigma increased from 5.6 x 10(-13) to 5.0 x 10(-11)/Omega
      for Al2O3 and 1.1 x 10(-12) to 1.0 x 10(-7)/Omega for AlN with the temperature
      increased from 363 to 593K. The SE image contrast obtained via heating approach
      in high vacuum with an Everhart-Thornley SE-detector was better than that via
      conventional approach of electron-ion neutralization in low vacuum (LV) with a
      gaseous SE-detector. The differences of compensation temperatures for charge
      effects indicate dielectric and thermal properties, and band structures of
      insulators. The charge compensation mechanisms of heating approach mainly relate
      to accelerated release of trapped electrons on insulating surface and to increase
      of electron emission yield by heating.

PMID- 19577846
TI  - Initial experimental results on a magnetic beam separator spectrometer for the
      SEM.
AB  - This article describes preliminary experiments to test the concept of scanning
      electron microscope (SEM) using a round magnetic beam separator to perform energy
      spectroscopy. Two experiments with an add-on attachment inside a conventional SEM
      were performed, one to estimate the sector image aberrations and the other to
      capture an energy spectrum of scattered electrons. The experiments show that the
      sector image aberrations lie well below 2 nm and that it is possible to capture
      the energy spectrum of secondary electrons.

PMID- 19577847
TI  - Fourier-ratio deconvolution techniques for electron energy-loss spectroscopy
      (EELS).
AB  - We discuss several ways of using Fourier-ratio deconvolution to process low-loss
      spectra. They include removal of the tail arising from the zero-loss peak,
      extraction of the spectrum of a particle from data recorded from the particle on
      a substrate, separation of the bulk and surface components in spectra recorded
      from samples of the same composition but different thickness, and investigation
      of interface energy-loss modes. We also demonstrate the use of a Bayesian
      equivalent procedure based on the Richardson-Lucy algorithm.

PMID- 19577848
TI  - Effect of imiquimod on partial-thickness burns.
AB  - BACKGROUND: Burns can result in substantial morbidity through fibroblast
      proliferation and contracture. Imiquimod (IMQ), an immune response modifier and
      upregulator of endogenous cytokine expression, has been shown to suppress
      fibroblast proliferation. It is widely used in the treatment of viral, neoplastic
      and non-neoplastic skin conditions and has recently been tested in the reduction
      of hypertrophic scarring and keloids. To our knowledge, no other study has so far
      evaluated the effect of IMQ on cutaneous burns. METHODS: Partial-thickness burns
      were produced on the dorsum of 32 Wistar rats. Right-sided wounds received saline
      and left-sided wounds received 5% IMQ cream three times/week following injury.
      Photographs taken on post-burn days (PBD) 4, 7, 14 and 21 were evaluated for
      wound appearance using a clinical assessment scale and a visual analog scale.
      Scars were measured by digital planimetry. Samples stained with hematoxylin-eosin
      were submitted to conventional histological analysis. Samples stained with Sirius
      Red were analyzed under polarized light for collagen morphometry. RESULTS: Visual
      scores were higher in the saline group on PBD 21 (p<0.05). Wound edge migration
      rates were lower (p<0.05) and conventional histology showed accentuated
      inflammation and delayed reepithelialization in the IMQ group. Type-I and type
      III collagen deposition increased in the saline group and decreased in the IMQ
      group. Conversely, the proportion between type-I and type-III collagen differed
      significantly between treatments on PBD 4 and 21 (p<0.05 in both cases).
      CONCLUSIONS: Short-term topical imiquimod treatment of partial-thickness burns in
      rats did not improve clinical appearance and scarring but rather decreased
      fibrosis. Significant differences in collagen deposition were observed between
      the treatments.

PMID- 19577849
TI  - Involving burn survivors in agenda setting on burn research: an added value?
AB  - BACKGROUND AND AIM: The role of burn survivors in burn research is usually
      restricted to being objects of study and beneficiaries of research results, while
      decision-making on research is traditionally the domain of a small group of
      experts, mainly scientists. In this article we compare the research priorities of
      burn survivors and professionals and investigate to what extent it is possible to
      come to a joint research agenda. METHODOLOGY: The project followed the Dialogue
      Model for research agenda setting. Initially burn survivors and professionals
      were consulted separately and group-specific lists of research priorities were
      established, using a literature survey, exploratory interviews (n=10), focus
      groups (n=58), a questionnaire (n=224) and Delphi rounds (n=12). Subsequently, in
      a dialogue meeting burn survivors and professionals presented and discussed their
      priorities, developed one integrated list, and prioritized the 15 most important
      topics on this list. RESULTS: Considerable overlap was observed between the
      research priorities of burn survivors and professionals, particularly with
      respect to biomedical and clinical research on wound healing and scar management.
      However, differences were also observed, e.g. treatment of itching and oedema on
      scars and donor places. CONCLUSION: The model proved useful in eliciting research
      priorities from both professionals and burn survivors, and in stimulating a
      meaningful dialogue between these groups. The involvement of burn survivors
      identified burn research areas that are currently not the focus of research in
      The Netherlands.

PMID- 19577850
TI  - Cell-phone based multimedia messaging service (MMS) and burn injuries.

PMID- 19577851
TI  - Evidence for a key role of steroids in the modulation of pain.
AB  - Neurotransmitters such as glutamate, substance P, serotonin and gamma
      aminobutyric acid pivotally control pain mechanisms. It is also well known that
      inflammatory and/or neuropathic pain may depend on the action of diverse
      cytokines and other molecules including eicosanoids, endorphins, calcitonin-gene
      related peptide, free radicals and transcription factors. Because steroids
      control the development, activities and plasticity of the nervous system, these
      compounds are of particular interest in the modulation of pain. The paper
      discusses various data supporting the existence of key regulatory effects of
      steroids in the control of pain. In particular, we analyzed three categories of
      observations which historically contributed to demonstrate that endogenous and
      synthetic steroids play a crucial role in the regulation of neurobiological
      processes involved in pain sensation. The first series of data, which present the
      chemical characteristics enabling steroids to act on several tissues, also
      summarize pertinent results supporting the modulation of pain sensation by
      steroidal compounds. The second category of data evokes psychosocial, fundamental
      and clinical results suggesting the existence of sex steroid-based differences in
      pain perception. Finally, we discuss recent evidence showing the endogenous
      production of neurosteroids and their effects in the spinal cord which crucially
      controls pain transmission. Taken together, the data reviewed herein suggest that
      future investigations aiming to develop effective steroid-based strategies
      against chronic pain must integrate in a complementary manner anti-inflammatory
      properties of steroids, sex steroid-induced dimorphism in pain perception and
      regulatory effects exerted by endogenous neurosteroids in pain neural circuits.

PMID- 19577852
TI  - A combination of PPAR-gamma agonists and HMG CoA reductase inhibitors (statins)
      as a new therapy for the conservative treatment of AAS (aortic aneurysm
      syndromes).
AB  - The aetiology of aortic aneurysms (AAs) is the subject of intense clinical
      investigation. One of the critical points in their pathogenesis is the disruption
      of the balance between vascular extracellular matrix deposition and degradation.
      AAs are common features in some genetically determined diseases of the connective
      tissue, such as Marfan and Loeys-Dietz Syndromes. Acquired factors determining an
      enhanced inflammatory state of the arterial wall also play a key role. Previous
      studies have determined the role of TGF-beta as the principal mediator of the
      pathogenesis of the alterations of the arterial wall homeostasis in aneurysms.
      The current medical management of any AA is mainly focused on the use of
      pharmacological agents that reduce hemodynamic stress of aortic wall, since
      hypertension is the major risk factor for the enlargement and rupture of the AAs.
      Thus, this approach is useful to reduce the risk of aneurysm rupture but is far
      from being a comprehensive pathophysiology-based therapeutic approach. Drugs with
      the potential of reducing the action of TGF-beta, which activation and expression
      has been reported to have a major role in the molecular pathogenesis of the
      aneurysms, improving matrix repair, decreasing the proteolytic pattern and
      inhibition of angiotensin converting enzyme as well as preventing angiotensin II
      induced AT1R (angiotensin type 1 receptor) activation, can represent new options
      in the medical therapy of AAs. We propose that a combination of statins and PPAR
      gamma agonist could be a useful adjunctive therapy in this condition. The new
      pathophysiology-based therapeutic approach, involving the pathological patterns
      and mechanisms leading to the rupture of the AAs, could represent an interesting
      additional tool in combination with the current established anti-hypertensive
      therapy.

PMID- 19577853
TI  - The expression of p63 and p53 in keratoacanthoma and intraepidermal and invasive
      neoplasms of the skin.
AB  - p53 is a well-known tumor suppressor gene, and its mutation is a common event in
      intraepidermal and invasive neoplasms of the skin. p63 is a homologue of the
      tumor suppressor gene p53, which is expressed in human basal squamous epithelium,
      and despite its homology to p53, it is considered to act as an oncogene. We
      evaluated p63 and p53 expression in usual skin cancers, including basal cell
      carcinoma (BCC), squamous cell carcinoma (SCC), keratoacanthoma (KA), and
      intraepidermal neoplasms, including Bowen's disease (BD), actinic keratosis (AK),
      malignant melanoma in situ (MM in situ), and Paget's disease (PD) to clarify the
      putative role of p63 and p53 in the development and differential diagnosis of
      these lesions. Seventeen SCC, 23 BCC, 16 KA, 26 AK, 22 BD, 7 MM in situ, and 6 PD
      were included in this study. We determined decreasing p63 staining in BD, AK,
      BCC, SCC, and KA, respectively. None of the MM in situ and PD was positive for
      p63. The mean p53 staining was highest in BD, followed by AK, SCC, PD, KA, BCC,
      and normal skin. There was no correlation between the groups in terms of p63 and
      p53 staining. Based on our findings, analysis of p63 expression may be helpful in
      the differential diagnosis of BD and AK versus MM in situ and PD, particularly in
      small biopsies.

PMID- 19577854
TI  - Spontaneous hepatic hemorrhage secondary to prolonged use of oral contraceptives.
AB  - Oral contraceptive pills (OCP) are the most commonly used form of contraception
      throughout the United States of America. The prolonged usage of oral
      contraceptives leads to a variety of complications, ranging from subclinical
      modifications of liver function tests to the development of benign and malignant
      tumors of the liver. Spontaneous hepatic hemorrhage secondary to oral
      contraceptive use was only reported once in the early 1980s. We report a case of
      spontaneous hepatic hemorrhage secondary to prolonged ingestion of combined OCPs
      followed by multiple pulmonary emboli without underlying thrombophilia.

PMID- 19577855
TI  - Impact of fraction size on lung radiation toxicity: hypofractionation may be
      beneficial in dose escalation of radiotherapy for lung cancers.
AB  - PURPOSE: To assess how fraction size impacts lung radiation toxicity and
      therapeutic ratio in treatment of lung cancers. METHODS AND MATERIALS: The
      relative damaged volume (RDV) of lung was used as the endpoint in the comparison
      of various fractionation schemes with the same normalized total dose (NTD) to the
      tumor. The RDV was computed from the biologically corrected lung dose-volume
      histogram (DVH), with an alpha/beta ratio of 3 and 10 for lung and tumor,
      respectively. Two different (linear and S-shaped) local dose-effect models that
      incorporated the concept of a threshold dose effect with a single parameter
      D(L50) (dose at 50% local dose effect) were used to convert the DVH into the RDV.
      The comparison was conducted using four representative DVHs at different NTD and
      D(L50) values. RESULTS: The RDV decreased with increasing dose/fraction when the
      NTD was larger than a critical dose (D(CR)) and increased when the NTD was less
      than D(CR). The D(CR) was 32-50 Gy and 58-87 Gy for a small tumor (11 cm(3)) for
      the linear and S-shaped local dose-effect models, respectively, when D(L50) was
      20-30 Gy. The D(CR) was 66-97 Gy and 66-99 Gy, respectively, for a large tumor
      (266 cm(3)). Hypofractionation was preferred for small tumors and higher NTDs,
      and conventional fractionation was better for large tumors and lower NTDs.
      Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80
      90 Gy, especially if the D(L50) is small (20 Gy). CONCLUSION: This computational
      study demonstrated that hypofractionated stereotactic body radiotherapy is a
      better regimen than conventional fractionation in lung cancer patients with small
      tumors and high doses, because it generates lower RDV when the tumor NTD is kept
      unchanged.

PMID- 19577856
TI  - Whole-brain radiotherapy with simultaneous integrated boost to multiple brain
      metastases using volumetric modulated arc therapy.
AB  - PURPOSE: Volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems,
      Palo Alto, CA) allows for the generation of intensity-modulated dose
      distributions by use of a single gantry rotation. We used RA to plan and deliver
      whole-brain radiotherapy (WBRT) with a simultaneous integrated boost in patients
      with multiple brain metastases. METHODS AND MATERIALS: Composite RA plans were
      generated for 8 patients, consisting of WBRT (20 Gy in 5 fractions) with an
      integrated boost, also 20 Gy in 5 fractions, to the brain metastases, and
      clinically delivered in 3 patients. Summated gross tumor volumes were 1.0 to 37.5
      cm(3). RA plans were measured in a solid water phantom by use of Gafchromic films
      (International Specialty Products, Wayne, NJ). RESULTS: Composite RA plans could
      be generated within 1 hour. Two arcs were needed to deliver the mean of 1,600
      monitor units with a mean "beam-on" time of 180 seconds. RA plans showed
      excellent coverage of planning target volume for WBRT and planning target volume
      for the boost, with mean volumes receiving at least 95% of the prescribed dose of
      100% and 99.8%, respectively. The mean conformity index was 1.36. Composite plans
      showed much steeper dose gradients outside the brain metastases than plans with a
      conventional summation of WBRT and radiosurgery. Comparison of calculated and
      measured doses showed a mean gamma for double-arc plans of 0.30, and the area
      with a gamma larger than 1 was 2%. In-room times for clinical RA sessions were
      approximately 20 minutes for each patient. CONCLUSIONS: RA treatment planning and
      delivery of integrated plans of WBRT and boosts to multiple brain metastases is a
      rapid and accurate technique that has a higher conformity index than conventional
      summation of WBRT and radiosurgery boost.

PMID- 19577858
TI  - Radiotherapy can decrease locoregional recurrence and increase survival in
      mastectomy patients with T1 to T2 breast cancer and one to three positive nodes
      with negative estrogen receptor and positive lymphovascular invasion status.
AB  - PURPOSE: To define a subgroup of patients at high risk of locoregional recurrence
      (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast
      cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2
      N1). METHODS AND MATERIALS: Between April 1991 and December 2005, 544 patients
      with T1-2 N1 invasive breast cancer were treated with modified radical
      mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and
      161 patients (29.6%) received radiotherapy. We retrospectively compared these two
      patient groups. RESULTS: With a median follow-up of 40.3 months, LRR occurred in
      40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04),
      negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular
      invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with
      a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and
      presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with
      statistical significance in the multivariate analysis. Radiotherapy reduced the
      LRR in patients with the following characteristics: age <40 years, T2 stage, high
      nuclear grade, negative ER status, and presence of LVI. For 41 patients with
      negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25
      (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to
      87.1%. CONCLUSION: Radiotherapy can reduce LRR and increase survival in T1-2 N1
      breast cancer patients with negative ER status and presence of LVI.

PMID- 19577857
TI  - Oropharyngeal squamous cell carcinoma treated with radiotherapy or
      radiochemotherapy: prognostic role of TP53 and HPV status.
AB  - PURPOSE: To study the prognostic value of the TP53 mutation and human papilloma
      virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND
      MATERIALS: The TP53 mutation and HPV status were analyzed in 78 cases of
      locoregionally advanced OPSCC. The possible correlation of these factors with
      locoregiownal control, relapse-free survival, disease-specific survival, and
      overall survival (OS) was also investigated. RESULTS: Of these 78 cases, 22 had
      disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34
      cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV
      positive (HPV+) cases carried a functional p53 protein, except for 1 case that
      had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-)
      patients in terms of all survival parameters, with highly statistically
      significant differences between the groups. Specifically, no distant metastases
      were observed in the HPV+ patients, whereas they occurred in 17% of the HPV-
      patients. However, no difference was observed between the WT TP53 and mutation
      group, even when this was analyzed in terms of disruptive and non-disruptive
      mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS
      rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the
      mutation group showed improvement in all survival parameters. In addition, the
      second tumor-free 5-year survival rate was 72% in HPV- cases, but no second
      tumors were observed in HPV+ and WT p53 cases. CONCLUSIONS: Patients with HPV+
      OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based
      chemotherapy may not confer a satisfactory outcome, especially in WT cases,
      thereby justifying the additional or alternative use of taxanes and epidermal
      growth factor receptors inhibitors. Uncommon distant metastases and second tumors
      in the HPV+ group may be cause for clinicians to review the follow-up policies in
      these patients.

PMID- 19577859
TI  - Measuring time to biochemical failure in the TROG 96.01 trial: when should the
      clock start ticking?
AB  - PURPOSE: We sought to determine whether short-term neoadjuvant androgen
      deprivation (STAD) duration influences the optimal time point from which Phoenix
      fail (time to biochemical failure; TTBF) should be measured. METHODS AND
      MATERIALS: In the Trans-Tasman Radiation Oncology Group 96.01 trial, men with
      locally advanced prostate cancer were randomized to 3 or 6 months STAD before and
      during prostatic irradiation (XRT) or to XRT alone. The prognostic value of TTBF
      measured from the end of radiation (ERT) and randomization were compared using
      Cox models. RESULTS: Between 1996 and 2000, 802 eligible patients were
      randomized. In 436 men with Phoenix failure, TTBF measured from randomization was
      a powerful predictor of prostate cancer-specific survival and marginally more
      accurate than TTBF measured from ERT in Cox models. Insufficient data were
      available to confirm that TTBF measured from testosterone recovery may also be a
      suitable option. CONCLUSIONS: TTBF measured from randomization (commencement of
      therapy) performed well in this trial dataset and will be a convenient option if
      this finding holds in other datasets that include long-term androgen deprivation
      data.

PMID- 19577860
TI  - On the importance of accounting for competing risks in pediatric cancer trials
      designed to delay or avoid radiotherapy: I. Basic concepts and first analyses.
AB  - PURPOSE: In trials designed to delay or avoid irradiation among children with
      malignant brain tumor, although irradiation after disease progression is an
      important event, patients who have disease progression may decline radiotherapy
      (RT), or those without disease progression may opt for elective RT. To accurately
      describe the cumulative need for RT in such instances, it is crucial to account
      for these distinct events and to evaluate how each contributes to the delay or
      advancement of irradiation via a competing risks analysis. METHODS AND MATERIALS:
      We describe the summary of competing events in such trials using competing risks
      methods based on cumulative incidence functions and Gray's test. The results
      obtained are contrasted with standard survival methods based on Kaplan-Meier
      curves, cause-specific hazard functions and log-rank test. RESULTS: The Kaplan
      Meier method overestimates all event-specific rates. The cause-specific hazard
      analysis showed reduction in hazards for all events (A: RT after progression; B:
      no RT after progression; C: elective RT) among children with ependymoma. For
      event A, a higher cumulative incidence was reported for ependymoma. Although
      Gray's test failed to detect any difference (p = 0.331) between histologic
      subtypes, the log-rank test suggested marginal evidence (p = 0.057). Similarly,
      for event C, the log-rank test found stronger evidence of reduction in hazard
      among those with ependymoma (p = 0.005) as compared with Gray's test (p = 0.086).
      CONCLUSIONS: To evaluate treatment differences, failing to account for competing
      risks using appropriate methodology may lead to incorrect interpretations.

PMID- 19577861
TI  - Consideration of the role of radiotherapy for abdominal lymph node metastases in
      patients with recurrent gastric cancer.
AB  - PURPOSE: To evaluate the outcome of external beam radiotherapy for abdominal
      lymph node (LN) metastases in patients with recurrent gastric cancer. METHODS AND
      MATERIALS: The clinical data of 79 patients with abdominal LN metastases
      developing after curative resection of gastric tumor were retrospectively
      analyzed. Of the 79 patients, 37 received radiation (40-60 Gy in fractions of 2.0
      Gy daily, five times weekly; termed the radiation group), and 42 received
      chemotherapy or supportive care (the nonradiation group). The Kaplan-Meier method
      was used to evaluate survival, and a Cox regression model was used to identify
      predictors of prognosis. RESULTS: After radiation, complete response and partial
      response were observed in 29.7% and 54.1% of patients, respectively. Clinical
      symptoms were relieved in 19 of 21 patients (90.5%) after completing radiation.
      Median survival time was 11.4 months in the radiation group and 4.8 months in the
      nonradiation group. Overall survival for patients with and without radiation was
      43.2% and 19.0% at 1 year and 27.6% and 4.1% at 2 years, respectively (p =
      0.002). Multivariate analysis showed that the relative risk of death in the
      radiation group from the time of diagnosis of LN metastases was 0.253 (p <
      0.001). The most common adverse effect of radiation was gastrointestinal
      toxicity, but it was mild in most patients. CONCLUSIONS: Abdominal LN metastases
      from gastric cancer are sensitive to radiation. Delivery of 50 Gy is effective as
      palliative treatment and may prolong overall survival.

PMID- 19577862
TI  - Comparison of methods to reduce dose to swallowing-related structures in head and
      neck cancer.
AB  - INTRODUCTION: Emerging data suggest that reduction of dose to the larynx and
      pharyngeal constrictor may lower the risk of swallowing complications such as
      long-term gastrostomy dependence and aspiration. Organ avoidance becomes
      difficult when the primary tumor or involved nodes are present at the level of
      the larynx. MATERIALS AND METHODS: Fifteen patients with Stage III-IV squamous
      cell carcinoma of the head and neck with high-dose target volume at the level of
      the larynx (but not involving the glottic larynx) were planned with whole-field
      IMRT (WF-IMRT), as well as a low anterior neck field dynamically matched to an
      IMRT plan (D-SCLV). Plans were compared with respect to coverage of targets and
      sparing of normal tissues including the larynx, inferior pharyngeal constrictor
      (IPC), parotid, and cord. RESULTS: There was no significant difference between
      the two techniques in coverage of the high- or intermediate-dose planning target
      volumes (PTVs). Coverage of the elective nodal PTV was inferior with the D-SCLV
      technique, with a mean of 96.5% vs. 86.3% of the volume receiving the
      prescription dose (p = 0.001) compared with WF-IMRT plans. However, the D-SCLV
      technique significantly reduced mean dose to the larynx (43.7 vs. 46.7 Gy, p =
      0.05) and IPC (39.1 vs. 46.1 Gy, p = 0.002). There was no significant difference
      in dose to the parotid or cord. CONCLUSION: Given the steep dose responses seen
      in studies examining the association between swallowing toxicity and dose to the
      larynx and IPC, dose reductions using the D-SCLV technique may be clinically
      significant.

PMID- 19577863
TI  - Primary tumor necrosis predicts distant control in locally advanced soft-tissue
      sarcomas after preoperative concurrent chemoradiotherapy.
AB  - PURPOSE: Various neoadjuvant approaches have been evaluated for the treatment of
      locally advanced soft-tissue sarcomas. This retrospective study describes a
      uniquely modified version of the Eilber regimen developed at the University of
      Chicago. METHODS AND MATERIALS: We treated 34 patients (28 Stage III and 6 Stage
      IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and
      2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2
      per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions),
      sandwiched between various chemotherapy regimens. Postoperatively, 47% received
      further adjuvant chemotherapy. RESULTS: Most tumors (94%) were Grade 3, and all
      were T2b, with a median size of 10.3 cm. Wide excision was performed in 29
      patients (85%), and 5 required amputation. Of the resected tumor specimens, 50%
      exhibited high (> or =90%) treatment-induced necrosis and 11.8% had a complete
      pathologic response. Surgical margins were negative in all patients. The 5-year
      survival rate was 42.3% for all patients and 45.2% for Stage III patients. For
      limb-preservation patients, the 5-year local control rate was 89.0% and
      reoperation was required for wound complications in 17.2%. The 5-year freedom
      from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom
      from distant metastasis was superior if treatment-induced tumor necrosis was 90%
      or greater (84.6% vs. 19.9%, p = 0.02). CONCLUSIONS: This well-tolerated
      concurrent chemoradiotherapy approach yields excellent rates of limb preservation
      and local control. The resulting treatment-induced necrosis rates are predictive
      of subsequent metastatic risk, and this information may provide an opportunity to
      guide postoperative systemic therapies.

PMID- 19577864
TI  - Phase II study of vinorelbine and estramustine in combination with conformational
      radiotherapy for patients with high-risk prostate cancer.
AB  - PURPOSE: To evaluate the efficacy and safety profile of vinorelbine and
      estramustine in combination with three-dimensional conformational radiotherapy
      (3D-CRT) in patients with localized high-risk prostate cancer. METHODS AND
      MATERIALS: Fifty patients received estramustine, 600 mg/m(2) daily, and
      vinorelbine, 25 mg/m(2), on days 1 and 8 of a 21-day cycle for three cycles in
      combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy
      fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received
      luteinizing hormone-releasing hormone analogs for 3 years. RESULTS: All patients
      were evaluated for response and toxicity. Progression-free survival at 5 years
      was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only
      biochemical relapse. The most frequent severe toxicities were cystitis (16% of
      patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia
      (8% of patients), and proctitis (8% of patients). Six patients (12%) did not
      complete study treatment due to the patient's decision (n = 1) and to adverse
      events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial
      infarction. CONCLUSIONS: Vinorelbine and estramustine in combination with 3D-CRT
      is a safe and effective regimen for patients with localized high-risk prostate
      cancer. A randomized trial is needed to determine whether the results of this
      regimen are an improvement over the results obtained with radiotherapy and
      androgen ablation.

PMID- 19577865
TI  - Long-term toxicity following 3D conformal radiation therapy for prostate cancer
      from the RTOG 9406 phase I/II dose escalation study.
AB  - PURPOSE: To update the incidence of late toxicity of RTOG 9406, a three
      dimensional conformal radiation therapy (3DCRT) dose escalation trial for
      prostate cancer. METHODS AND MATERIALS: A total of 1,084 men were registered to
      this Phase I/II trial of 3DCRT (eligible patients, 1,055). The dose for level I
      was 68.4 Gy; 73.8 Gy for level II; 79.2 Gy for level III; 74 Gy for level IV; and
      78 Gy for level V. Patients in levels I to III received 1.8 Gy/fraction, and
      those in levels IV to V received 2.0 Gy/fraction. Disease group I patients were
      treated at the prostate only, group 2 patients were treated at the prostate and
      at the seminal vesicles with a prostate boost, and group 3 patients were treated
      at the prostate and seminal vesicles. The median follow-up period for surviving
      patients was 6.1 y (level V) to 12.1 y (level I). RESULTS: The incidence rates of
      RTOG grade 3 or less gastrointestinal or genitourinary toxicity were 3%, 4%, 6%,
      7%, and 9% in group 1 and 6%, 2%, 6%, 9%, and 12% in group 2 at dose levels of I,
      II, III, IV, and V, respectively. In group 1, level V patients had a higher
      probability of grade 2 late or greater gastrointestinal or genitourinary toxicity
      than those in levels I, II, and III (hazard ratio [HR] = 1.93, p = 0.0101; HR =
      2.29, p = 0.0007; HR = 2.52, p = 0.0002, respectively). In group 2, dose level V
      patients had a higher probability of grade 2 or greater late gastrointestinal or
      genitourinary toxicity than those in dose levels II, III, and IV (HR = 2.61, p =
      0.0002; HR = 2.22, p = 0.0051; HR = 1.60, p = 0.0276, respectively). CONCLUSIONS:
      Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade
      2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to
      79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.

PMID- 19577866
TI  - True local recurrence rate in the conserved breast after magnetic resonance
      imaging-targeted radiotherapy.
AB  - PURPOSE: Better accuracy of local radiotherapy may substantially improve local
      control and thus long-term breast cancer survival. Magnetic resonance imaging
      (MRI) has high resolution and sensitivity in breast tissue and may depict the
      tumor bed more accurately than conventional planning techniques. A postoperative
      complex (POCx) comprises all visible changes thought to be related to surgery
      within the breast and acts as a surrogate for the tumor bed. This study reports
      on local recurrence rates after MRI-assisted radiotherapy planning to ensure
      adequate coverage of the POCx. METHODS AND MATERIALS: Simple opposed tangential
      fields were defined by surface anatomy in the conventional manner in 221
      consecutive patients. After MRI, fields were modified by a single radiation
      oncologist to ensure encompassment of the POCx with a 10-mm margin. Genetic
      analysis was performed on all local relapses (LRs) to distinguish true
      recurrences (TRs) from new primaries (NPs). RESULTS: This was a high risk cohort
      at 5 years: only 9.5% were classified as low risk (St Gallen): 43.4% were Grade 3
      and 19.9% had surgical margins <1 mm; 62.4% of patients received boosts.
      Adjustments of standard field margins were required in 69%. After a median follow
      up of 5 years, there were 3 LRs (1.3%) as the site of first relapse in 221
      patients, comprising two TRs (0.9%) and one NP (0.4%). CONCLUSIONS: Accurate
      targeting of the true tumor bed is critical. MRI may better define the tumor bed.

PMID- 19577867
TI  - Hypothyroidism as a consequence of intensity-modulated radiotherapy with
      concurrent taxane-based chemotherapy for locally advanced head-and-neck cancer.
AB  - PURPOSE: To conduct a retrospective review of 168 consecutively treated locally
      advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated
      radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for
      developing hypothyroidism. METHODS AND MATERIALS: Intensity-modulated
      radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and
      56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of
      IMRT plans were used to determine radiation dose to thyroid and were compared
      with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of
      these same patients randomly selected for replanning and with DVHs of 16 patients
      in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30
      mg/m(2)) and carboplatin area under the curve-1 were given concurrently with
      IMRT. RESULTS: Sixty-one of 128 evaluable patients (47.7%) developed
      hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9
      years). Age and volume of irradiated thyroid were associated with hypothyroidism
      development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose
      constraints resulted in significantly higher minimum, maximum, and median dose (p
      < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05).
      Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median
      dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but
      higher minimum and maximum dose (p < 0.005). CONCLUSIONS: If not protected, IMRT
      for LAHNC can result in higher radiation to the thyroid than with conventional 3D
      RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT
      are achievable and recommended.

PMID- 19577868
TI  - Fertility after post-cervical artificial insemination with cryopreserved sperm
      from boar ejaculates of good and poor freezability.
AB  - This study compared the field fertility outcomes in frozen-thawed (FT) sperm from
      boar ejaculates with different freezability (good, GFE/poor, PFE) while testing
      the reliability of the post-cervical artificial insemination (post-CAI) in FT
      sperm. The assay was conducted over eight months with 86 weaned sows being
      inseminated by post-CAI. Every ejaculate in a total of 26 from 15 Pietrain boars
      was divided into a refrigerated semen portion (FS; control treatment) and a
      cryopreserved portion (FT sperm), and the ejaculates were in turn classified as
      GFE or PFE in function of the sperm progressive motility and viability at 240min
      post-thaw. As result, one of four possible treatments was randomly given to each
      sow: FS-GFE, FS-PFE, FT-GFE and FT-PFE. The number of pregnant and farrowing sows
      in FT-GFE did not significantly differ from those of FS control treatments.
      Contrarily, the probabilities of pregnancy were two times lower after
      inseminations with FT-PFE (P<0.05) compared to FT-GFE, which indicates that
      ejaculates with high post-thaw sperm progressive motility and viability are more
      likely to result in pregnancies than those with poor in vitro sperm function.
      There were no differences in litter size or the risk of backflow among
      treatments. Further trials are required to determine the optimal volume and
      concentration of FT sperm in post-CAI to obtain a more reliable method for
      farmers interested in cryopreserved sperm.

PMID- 19577869
TI  - Pregnancy and conception rate after two intravaginal inseminations with dog semen
      frozen either with 5% glycerol or 5% ethylene glycol.
AB  - The primary goal of this study was to compare the effects of 5% ethylene glycol
      (EG) and 5% glycerol (G) on fertility of frozen-thawed dog semen following
      intravaginal insemination. The sperm-rich fraction of the ejaculate of three male
      dogs was collected, pooled and divided into two aliquots, and then frozen with a
      Tris-glucose-egg yolk-citric acid extender containing either 5% G or 5% EG. A
      total of 10 bitches were inseminated twice, five with G-frozen-thawed semen and
      five with EG-frozen-thawed semen; intravaginal inseminations were performed the
      4th and the 5th day after the estimated LH peak; four straws, thawed in a 37
      degrees C water bath for 1 min and diluted in a Tris buffer, were used for
      insemination (200 x 10(6) spermatozoa); the insemination dose was introduced in
      the cranial vagina of the bitch using a sterile plastic catheter.
      Ovariohysterectomy was performed in all bitches between days 29 and 31 after the
      calculated LH surge, and pregnancy status, and the number of conceptuses and
      corpora lutea were recorded. All bitches were pregnant. Neither the number of
      conceptuses, nor the ratio of conceptuses to corpora lutea (conception rate) was
      significantly different between groups. In this first screening, with a limited
      number of bitches, EG-frozen semen did not show a higher fertility than G-frozen
      semen when used for two intravaginal inseminations. Irrespective of the semen
      used, conception rate was 0.50.

PMID- 19577871
TI  - Hepatitis B: liver fibrosis and hepatocellular carcinoma.
AB  - Chronic hepatitis B virus (HBV) infection is estimated to be the cause of 55-60%
      of hepatocellular carcinoma (HCC) in the world. It has been estimated that up to
      40% of HBV-related HCC occur in persons who do not have cirrhosis while almost
      all cases of hepatitis C virus (HCV)-related HCC occur in the setting of
      cirrhosis. Data on the performance of non-invasive tests for liver fibrosis in
      patients with hepatitis B are limited. FibroTest may be superior to the Forns
      index, APRI, Goteborg University Cirrhosis Index (GUCI) and Hui model in
      detecting significant fibrosis (Metavir>F2) or cirrhosis (Metavir F4) but an
      algorithm that uses APRI for screening, FibroTest for confirmation, and biopsy
      for indeterminate cases has the greatest accuracy. Liver stiffness correlates
      with fibrosis stages but may be influenced by necroinflammatory activity with
      falsely high values in patients with alanine aminotransferase (ALT) flares and
      falsely low values in patients with viral suppression and ALT normalization
      during antiviral therapy. Therefore, additional studies are needed to determine
      the clinical settings in which liver stiffness measurement can accurately predict
      liver fibrosis and to establish cutoff values for differentiating different
      stages of fibrosis or cirrhosis. These studies should also compare the
      performance of liver stiffness measurement with serum markers of fibrosis in
      patients with varying degrees of necroinflammation and in untreated patients as
      well as patients receiving antiviral therapy. Until recently, older age, male
      gender and cirrhosis were the major risk factors associated with HCC development.
      Recent studies showed that HBV replication status, HBV genotype and mutations in
      the basal core promoter region play an important role in HCC development. These
      data indicate that algorithms incorporating demographics, viral factors, degree
      of necroinflammation and extent of fibrosis may be more accurate in predicting
      the risk of HBV-related HCC than fibrosis staging alone.

PMID- 19577870
TI  - New insight into the bony labyrinth: a microcomputed tomography study.
AB  - OBJECTIVES: To visualize and quantify the morphology and mineralization of the
      developing fetal human bony labyrinth, using 3D-microcomputed tomography (3D
      microCT) imaging. METHODS: Eleven right temporal bones from late second and third
      trimester fetuses were used in this prospective pilot study. After fixation in
      10% formalin solution, all samples underwent a microcomputed tomography (microCT)
      scan, permitting the 3D imaging of the bony labyrinth as well as the quantitative
      assessment of mineral density, angular distances and dimensions of inner ear
      components the progression of ossification was precised with histological
      observations. RESULTS: Our findings show different rates of growth among the
      semicircular canals, the vestibular aqueduct, the oval window, the round window
      and the cochlea. The final sizes of the cochlea and round window are achieved at
      23 weeks of gestation, with heights of 5mm and 2mm, respectively. The oval window
      reaches adult size at 35 weeks, whereas the vestibular aqueduct will attain adult
      size after birth. An increasing degree of torsion of each semicircular canal is
      observed during fetal development. The superior semicircular canal achieves adult
      size at 24 weeks, before the posterior and the lateral canals (25 weeks). The
      time-course of ossification and mineralization observed in structures and
      confirmed by histology. CONCLUSIONS: During this developmental period poorly
      studied until now, our findings suggest that each part of the bony labyrinth
      follows distinct growth and ossification kinetics trajectories, some of these
      reaching their adult size only after birth.

PMID- 19577872
TI  - Temporal subtraction chest radiography.
AB  - Radiologist are commonly required to compare a sequence of two or more chest
      radiographs of a given patient obtained over a period of time, which may range
      from a few hours to many years. In such cases, the task is one of detecting
      interval change. In the case of patients who have had a previous chest
      radiograph, an opportunity exists to enhance selectively areas of interval
      change, including regions with new or altered pathology, by using the previous
      radiographs as a subtraction mask. With temporal subtraction, the previous image
      is superimposed and registered with the current image, using automated two
      dimensional warping to compensate for any differences in positioning. A
      "difference image" is then created, by subtracting the previous from the current
      radiograph. In this temporal subtraction image, areas that are unchanged appear
      as uniform gray, while regions of new opacity, such as due to pneumonia or
      cancer, appear as prominent dark foci on a lighter background. By cancelling out
      the complex anatomical background, temporal subtraction can provide dramatically
      enhanced visibility of new areas of disease.

PMID- 19577873
TI  - Computer tomography in pulmonary invasive aspergillosis in hematological patients
      with neutropenia: an useful tool for diagnosis and assessment of outcome in
      clinical trials.
AB  - BACKGROUND AND OBJECTIVE: The exact timing of the evolution of lesion volumes of
      invasive pulmonary aspergillosis (IPA) on CT scan images could be helpful in the
      management of hematological patients but has never been evaluated in a
      prospective study. We analyzed the CT scan data from the prospective Combistrat
      trial. DESIGN AND METHODS: Volumes of aspergillosis lesions from 30 patients
      (including 24 acute myeloid leukaemia) with probable (n=26) or proven (n=4) IPA
      according to the EORTC-MSG modified criteria, were measured prospectively on the
      thoracic CT scans at the enrolment in the study on day 0 (D0), D7, D14 and end of
      treatment (EOT). RESULTS: For the overall population, the volume of pulmonary
      aspergillosis lesions increased significantly from D0 to D7 (1.6 fold; p=0.003).
      Then this volume decreased significantly from D7 to D14 (1.36 fold at D14 with
      p=0.003 for D14 vs. D7, but with p=0.56 for D14 vs. D0). At EOT (= D17, median
      value), the volume of lesions was significantly lower than D14 (0.76 fold the
      initial volume; p<0.001) but it was not significantly different when compared to
      D0 (p=0.11). CONCLUSIONS: The results of this prospective study suggest that the
      sequential analysis of CT scan in neutropenic patients with IPA depicts more
      precisely the evolution of lesion volumes than comparison to baseline images.
      Moreover, the systematic use of chest CT appears to be a useful tool for
      diagnosis and outcome evaluation of IPA in clinical trials.

PMID- 19577874
TI  - Meiothermus rufus sp. nov., a new slightly thermophilic red-pigmented species and
      emended description of the genus Meiothermus.
AB  - Four red-pigmented isolates, with optimum growth temperatures of approximately 55
      60 degrees C and an optimum pH for growth between 7.5 and 8.5, were recovered
      from hot springs in Central France. Phylogenetic analysis of the 16S rRNA gene
      sequences showed that these organisms represented a new species of the genus
      Meiothermus. The new isolates could be distinguished from other strains of the
      species of the genus Meiothermus primarily by the glycolipid profile and fatty
      acid composition because these organisms lacked the hydroxy fatty acids and the
      glycolipid variant GL-1a found in all other isolates of the species of
      Meiothermus examined. On the basis of the results presented here we propose the
      name Meiothermus rufus for the new species, which is represented by strains CAL
      4(T) (=DSM 22234(T)=LMG 24878(T)) and CAL-12 (=DSM 22235=LMG 24879). We also
      propose emending the genus Meiothermus to include strains that have only one
      glycolipid instead of two glycolipid variants.

PMID- 19577875
TI  - NMR analysis, protonation equilibria and decomposition kinetics of tolperisone.
AB  - The rate constants of spontaneous and hydroxide-catalyzed decomposition and the
      tautomer-specific protonation constants of tolperisone, a classical muscle
      relaxant were determined. A solution NMR method without any separation techniques
      was elaborated to quantitate the progress of decomposition. All the rate and
      equilibrium constants were determined at four different temperatures and the
      activation parameters were calculated. The molecular mechanism of decomposition
      is proposed.

PMID- 19577876
TI  - Determination of dexmedetomidine in human plasma using high performance liquid
      chromatography coupled with tandem mass spectrometric detection: application to a
      pharmacokinetic study.
AB  - A rapid, sensitive and selective high performance liquid chromatography
      electrospray ionization-tandem mass spectrometry method (HPLC-ESI-MS/MS) was
      developed and validated for the determination and pharmacokinetic investigation
      of dexmedetomidine (DMED) in human plasma. Dexmedetomidine and the internal
      standard (ondansetron) were extracted in a single step with diethyl-ether from
      1.0 mL of alkalinized plasma. The mobile phase was a mixture of acetonitrile and
      0.5% formic acid solution (30:70, v/v) at a flow rate of 0.2 mL min(-1). The
      detection was performed on a triple quadrupole tandem mass spectrometer in the
      selected reaction monitoring (SRM) mode using the respective [M+H]+ ions m/z
      201.0-->95.1 for DMED and m/z 294.1-->170.1 for the IS. The assay exhibited a
      linear dynamic range of 5-5000 pg mL(-1) with the correlation coefficient above
      0.9995. The lower limit of quantification (LLOQ) was 5 pg mL(-1) with a relative
      standard deviation of less than 15%. Acceptable precision and accuracy were
      obtained for concentrations over the standard curve range. The validated HPLC
      MS/MS method has been successfully applied to study the pharmacokinetics of three
      level doses of DMED in Chinese healthy volunteers.

PMID- 19577877
TI  - HERG1 gene expression as a specific tumor marker in colorectal tissues.
AB  - INTRODUCTION: Colorectal carcinomas exhibit a frequent recurrence after curative
      surgery, which may partially be due to histopathologically inconspicuous minimal
      residual disease. Reliable markers for tumor cells in colorectal tissue are still
      missing. Therefore, in this study we compared the predictive value of the
      putative tumor markers carcinoembryonic antigen (CEA), cytokeratin-19 (CK19) and
      cytokeratin-20 (CK20) to that of a novel marker, the human ether-a-go-go-related
      gene (HERG1) K(+) channel, a suggested regulator of tumor cell proliferation.
      MATERIALS AND METHODS: Using RT-PCR we studied HERG, CEA, CK19 and CK20
      expression in colorectal carcinomas and non-carcinoma controls. HERG1
      immunhistochemistry was performed in a total of 66 specimens, in colorectal
      carcinoma (n = 23), in matched histopathologically negative samples (n = 23)
      taken near the excision site from the same tumor patients and in healthy control
      biopsies (n = 20). In order to verify the relevance of HERG1 for tumor
      proliferation we studied the effect of HERG1 inhibition in the Colo-205 colon
      cancer carcinoma cell line using the MTT-assay. RESULTS: HERG1 was expressed in
      all tumor samples regardless of their stage and in adenomas larger than 0.4 cm,
      but absent in small adenomas, sigmadiverticulitis specimen and healthy
      histopathologically negative samples, except for one which developed a tumor
      recurrence. In contrast, CEA, CK19 and CK20 were absent in some tumors. The
      selective HERG1 inhibitor E-4031 dose-dependently impaired tumor growth in the
      proliferation assays. DISCUSSION: Our data indicate that HERG1, but not CEA, CK19
      or CK20, is a highly sensitive and reliable tumor biomarker that may constitute a
      novel molecular target for tumor treatment.

PMID- 19577878
TI  - [Centropontine myelinolysis and extrapontine myelinolysis complicating the quick
      correction of a hyponatremia].

PMID- 19577879
TI  - Distal interlocking screws with a modular revision stem for revision total hip
      arthroplasty in severe bone defects.
AB  - A prospective study of 15 patients was designed to examine whether the modular
      cementless revision stem (Revitan curved; Zimmer GmbH, Winterthur, Switzerland)
      is suitable for stem revisions with a defective isthmus when distal interlocking
      screws are also used for fixation. During a follow-up period of 35.4 +/- 11.4
      months (24-70 months), there was one stem loosening with screw breakage in a case
      of a stem that was too thin. According to Engh et al, bony ingrowth fixation of
      the stem occurred in 12 cases and stable fibrous fixation in 2 cases. The Harris
      Hip Score rose continuously from 44.7 +/- 12.9 points preoperatively to 75 +/- 10
      points at 24 months. This concept of additional stem fixation with distal
      interlocking screws represents a useful treatment option for revision
      arthroplasty in rare cases of a defective isthmus.

PMID- 19577880
TI  - Primitive results after medial-pivot knee arthroplasties: a minimum 5-year follow
      up study.
AB  - Paradoxical anterior movement of the femoral condyles after total knee
      arthroplasty (TKA) often attenuates the extension mechanism and causes a
      suboptimal outcome. The medial-pivot implant design aimed to confine anterior
      movement and emulate physiologic knee kinematics. In our study, a consecutive
      series of 58 medial-pivot TKA were enrolled with a minimum 5-year follow-up. The
      Knee Society score improved from 30.5 to 91.1 in objective and from 36.7 to 82.3
      in functional scale. The average range of motion was 115.4 degrees . The medial
      pivot TKA provided significant improvement in the postoperative range of motion,
      objective Knee Society score, pain scale, and functional score (P < .05)
      statistically. A larger sample and longer follow-up are recommended to draw
      definitive conclusions of this new implant design.

PMID- 19577881
TI  - Outcomes of routine use of antibiotic-loaded cement in primary total knee
      arthroplasty.
AB  - The routine use of antibiotic-loaded bone cement (ALBC) in primary total knee
      arthroplasty (TKA) is controversial. Outcomes were recorded in patients who
      underwent primary TKA from May 2003 to March 2007 using a community-based total
      joint registry. Infection rates were compared in patients undergoing TKA with
      ALBC and regular cement. A total of 22 889 primary TKA were performed, with 2030
      cases (8.9%) using ALBC. Two thousand four hundred forty-nine patients were
      diabetic (10.7%), with ALBC used in 295 cases (12%). The rate of deep infection
      was 1.4% for ALBC TKA (28 cases) and 0.7% (154 cases) with regular cement (P =
      .002). Among patients with diabetes, the infection rate was 1.7% (5 cases) with
      ALBC and 0.9% (19 cases) with regular cement (P = .199). In patients whom
      surgeons considered higher risk for infection, ALBC did not appear to reduce TKA
      infection rates. The routine use of antibiotic-laden cement warrants further
      investigation.

PMID- 19577882
TI  - Neurostenalgia of the femoral nerve: a treatable cause of intractable hip pain in
      a young adult.
AB  - Neurostenalgia of the femoral nerve is a compressive neuropathy that can result
      in debilitating pain. It often presents as hip pain, may coexist with other
      pathologic condition, and may be missed. Diagnosis and treatment affords great
      relief of symptoms. We present a patient with hip pain that persisted for 10
      years, despite multiple orthopedic interventions including pelvic osteotomy and
      arthroplasty. Femoral neurostenalgia was eventually identified, and pain was
      relieved after decompression of the nerve.

PMID- 19577883
TI  - Retrieval analysis of failed constrained acetabular liners.
AB  - Despite the large loads placed upon constrained acetabular liners, little is
      known of their mechanical performance. We analyzed retrieved liners to determine
      wear and other damage modes and assess associations between types and severity of
      damage and clinical, radiographic, and implant variables. Outer rim impingement
      frequency and severity were higher than that for the inner rim. The 20 degrees
      elevation was most frequently affected by impingement. Inner rim impingement was
      more frequent with small heads. Outer bearing surface wear scores were higher
      than inner bearing scores. Liners removed for infection or stem failure had
      similar damage compared with other groups, demonstrating the complex relationship
      of impingement and wear with clinical performance. No association was found
      between liner damage and clinical and radiographic variables.

PMID- 19577884
TI  - Adverse events after total knee arthroplasty: a national Medicare study.
AB  - Adverse events from 2033 total knee arthroplasty patients were documented by
      nonphysician abstractors. The annual rate of adverse events from 2002 to 2004 was
      9.2%, 6.4%, and 5.8%, respectively. Congestive heart failure (odds ratio, 2.1;
      95% confidence interval, 1.2-3.5; P < .01) and chronic obstructive pulmonary
      disease (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) were
      associated with a significantly increased risk of experiencing any adverse event
      during the index hospitalization. The 30-day postprocedure rate of readmission
      for all causes was 5.5%. Experiencing an adverse event during the index
      hospitalization increased the length of stay (P < .001). The rate of symptomatic
      venous thromboembolism 30 days postprocedure was 1.7%. The 30-day postprocedure
      mortality rate was 0.3%. Experiencing any adverse event was associated with an
      increased 30-day postprocedure mortality (P < .001). Compared with previous
      studies of Medicare claims, these data reveal a substantial decrease in the
      mortality rate, an increased readmission rate, and no substantial change in the
      rate of venous thromboembolism.

PMID- 19577885
TI  - Intraoperative muscle damage in total hip arthroplasty.
AB  - Tenderness in the medial and posterior thigh is sometimes observed during the
      early postoperative period after total hip arthroplasty (THA). In this study, the
      possible correlations of preoperative hip range of motion, surgical approach, and
      limb lengthening with postoperative muscle strain injury in THA were
      investigated. Sixty primary THA patients given the posterolateral approach or
      direct-lateral approach were examined. For comparison of the muscle strain injury
      in the 2 groups, we used magnetic resonance imaging. There were significant
      differences in postoperative thigh pain between cases in the posterolateral group
      with reduction of internal rotation and those with no reduction, and between
      cases in the direct-lateral group with reduction of external rotation and those
      with no reduction.

PMID- 19577886
TI  - Cemented polished tapered stems in patients less than 50 years of age: a minimum
      10-year follow-up.
AB  - We report the outcome of 58 consecutive polished tapered stems in 47 patients
      younger than 50 years, with a minimum of 10 years of follow-up. No stems were
      revised for aseptic loosening or osteolysis. The Harris hip scores were good or
      excellent in 76% of the patients. There was excellent preservation of proximal
      bone. Despite higher patient weight and frequent previous surgery, the outcome of
      polished tapered stems in patients younger than 50 years is comparable to the
      general population undergoing total hip arthroplasty and superior to other non
      polished tapered stem designs in young patients. Cup wear and cup failure were
      significantly worse in this group, with a higher incidence of periarticular
      osteolysis. Polished tapered stem designs are the benchmark for comparison to
      other arthroplasty options in young patients.

PMID- 19577887
TI  - Ceramic-on-ceramic total hip arthroplasty.
AB  - Ceramic bearing surfaces have been introduced to prevent bone loss after
      osteolysis seen with conventional polyethylene bearing surfaces. One hundred
      three ceramic-on-ceramic total hip arthroplasties in 97 patients were
      retrospectively reviewed. Average follow-up was 50.4 months. Preoperative Harris
      Hip Score was 49.5 points, which improved to 87.2 postoperatively (P < .05). Pain
      score improved from 13.7 points preoperatively to 40.6 points postoperatively (P
      < .05). Functional score improved from 30 points preoperatively to 41 points
      postoperatively (P < .05). No fractures, dislocations, infections, or osteolysis
      was observed on radiographs. Five patients (4.9%), at 11, 16, 30, 38, and 60
      months postoperatively, presented with "squeaky" hips that continue to perform
      well. Long-term studies will be required to determine the true efficacy of these
      hard bearing surfaces.

PMID- 19577888
TI  - Percutaneous in situ cementation of a loose femoral stem.
AB  - This case report describes a patient with aseptic loosening of the femoral
      component of her total hip arthroplasty 33 years after the initial implantation.
      The patient was treated with a percutaneous cementation technique using Cortoss
      (Orthovita, Malvern, Pa) synthetic cortical bone void filler.

PMID- 19577889
TI  - Polyethylene exchange in a second-generation cementless acetabular component.
AB  - Some have suggested that isolated polyethylene exchange in a well-fixed Harris
      Galante II acetabular component (Zimmer, Warsaw, Ind) necessitates cementing the
      liner or complete revision because the locking mechanism is suboptimal. We
      reviewed 29 hip revisions during which the polyethylene was exchanged using the
      native locking mechanism. Mean follow-up was 5.1 years (2-13 years). Of the 29
      patients, one had a disengagement of the revision polyethylene at 2.5 years. At
      the time of this patient's original revision, one of the tines was fractured, but
      a direct exchange was performed. There were 4 other revisions (one for loosening
      and 3 for instability). There were no other complications attributable to the
      direct polyethylene exchange and no further reoperations. This series suggests
      that polyethylene exchange with the Harris-Galante II prosthesis can be performed
      safely using the native locking mechanism in the absence of fractured tines.

PMID- 19577890
TI  - Decreased dislocation after revision total hip arthroplasty using larger femoral
      head size and posterior capsular repair.
AB  - The purpose of this study was to determine if the use of both a larger femoral
      head size and a posterior capsular repair would lead to a decreased incidence of
      dislocation following revision total hip arthroplasty (THA). Two hundred forty
      two consecutive revision THAs with posterolateral approach were performed between
      2000 and 2005. Group 1 had 132 revision THAs with posterolateral approach and 28
      mm head size without posterior capsule repair. Group 2 had 100 revision THAs with
      a 32-mm head size and repair of the remaining hip capsule. There were no
      statistically significant differences in the two groups. Group 1 had 14
      dislocations (10.6%). Group 2 had 3 dislocations (2.7%) (P < .05). Based on the
      results of this retrospective review, the authors recommend the use of both
      larger femoral head sizes and repair of any posterior capsular tissue available
      in patients undergoing revision hip arthroplasty.

PMID- 19577891
TI  - Long-term results of cemented total hip arthroplasty in developmental dysplasia
      with acetabular bulk bone grafts after improving operative techniques.
AB  - We present the long-term results (mean follow-up, 11.8 years; range, 6.3-15.4
      years) of cemented total hip arthroplasty with acetabular bulk bone grafting in
      147 dysplastic hips using improved surgical techniques. Operations were performed
      through a direct lateral approach with partial trochanteric osteotomy to avoid
      nonunion of the greater trochanter. Bioresorbable poly(l-lactide) screws were
      used for fixation of the acetabular bone grafts to prevent any possible delayed
      remodeling. Preoperative planning using computer simulation was performed to
      estimate the optimal size and position of the acetabular component. Analysis
      predicted rates of survival of the acetabular component of 96% and 91% at 15
      years, with revision for aseptic loosening and radiologic loosening as the end
      points, respectively. Our results indicate excellent long-term clinical and
      radiographic survivorship of a cemented acetabular component with bulk autograft
      for acetabular dysplasia.

PMID- 19577892
TI  - Undetected fracture of an alumina ceramic on ceramic hip prosthesis.
AB  - An unusual case of undetected ceramic fracture was discovered by coincidence
      during total hip arthroplasty revision for sepsis. To our knowledge, this kind of
      fracture has never been described before. The cup liner was broken in 2 parts,
      consisting of a large outer annulus and a smaller round central piece that was
      detached from the superior and posterior part of the cup, creating a hole in the
      cup. The analysis of the retrievals suggests that the fracture occurred during
      walking at the contact point between the head and the cup. The ceramic breakage
      was asymptomatic with no mechanical disorder, suggesting that some ceramic
      fracture may be tolerated in vivo. However, any evidence of a fractured ceramic
      component should cause the surgeon to strongly consider revision.

PMID- 19577893
TI  - A new technique of subtrochanteric shortening in total hip replacement for Crowe
      type 3 to 4 dysplasia of the hip.
AB  - A new technique of femoral fixation that uses a transverse osteotomy for
      subtrochanteric shortening and derotation in total hip arthroplasty for Crowe
      type 3 to 4 dysplasia of the hip is described. This series included 21 cases in
      12 women and 2 men, with a mean age of 42.3 years. Follow-up averaged 41.2
      months. Bone pegs prepared from the resected femoral segment were seated in the
      medullary canal around the stem for femoral fixation. Merle d'Aubigne scores for
      pain, motion, and walking improved from 2.9, 4.4, and 3.7 to 5.2, 5.4, and 5.5,
      respectively. Radiographic union was detected within 12 +/- 3.4 (range, 6-24)
      weeks in all cases. Complications were early dislocation in 2 cases. This
      technique allows correction of anteversion, provides excellent rotational
      stability, and eliminates the need for additional osteosynthesis regardless of
      the stem design.

PMID- 19577894
TI  - Long-term outcome of total knee arthroplasty in Charcot joint: a 10- to 22-year
      follow-up.
AB  - The results of 11 total knee arthroplasties in 9 patients with a Charcot joint
      secondary to neurosyphilis were reviewed. The mean age was 60.1 years, and follow
      up averaged 12.3 years. Endomodel rotating hinge prostheses (Waldemar Link GMBH
      and Co, Hamburg, Germany) were implanted in all knees. The mean knee score
      increased from 44.9 before surgery to 95.0 at the final follow-up, and the mean
      function score increased from 45.0 before surgery to 93.6 at the final follow-up.
      Complications were noted in 3 knees, including 2 dislocations of the knee and 1
      deep infection. The clinical results of total knee arthroplasty were satisfactory
      in most cases of Charcot joint. Rotating hinge prostheses are strongly
      recommended for use in Charcot joint. However, the procedure is technically
      demanding, and there were considerable complications.

PMID- 19577895
TI  - Learning curve with minimally invasive unicompartmental knee arthroplasty.
AB  - This study examined 445 consecutive minimally invasive unicompartmental knee
      arthroplasties (UKAs) from one institution to determine whether revision and
      reoperation rates would decrease as the number of cases performed increased,
      indicating the presence of a learning curve with this procedure. At a mean of
      3.25 years, 26 knees required revision yielding an overall revision rate of 5.8%;
      survivorship at 2 years with revision as an end point was 96% +/- 1.7%. Both
      revisions and reoperations decreased over time but not significantly. For the
      first half of UKA cases performed vs the second half, revision rates fell from
      5.0% to 2.5%, and reoperation rates fell from 8.1% to 5.4%. These data
      demonstrate that despite modifications made to improve surgical technique across
      time, a substantial complication rate with this procedure persists.

PMID- 19577896
TI  - Comparison of steady state femoral head penetration rates between two highly
      cross-linked polyethylenes in total hip arthroplasty.
AB  - Given that the manufacture of highly cross-linked polyethylene (HXLPE) is not
      standardized, the behavior of these materials may vary. Our study compares
      minimum 5-year steady state femoral head penetration rates using the Martell
      method, in 2 HXPLEs produced by different manufacturers. Patients received a
      primary hip arthroplasty using an uncemented acetabular component with an HXLPE
      liner and a 28-mm femoral head. Forty-seven patients in group A received an HXLPE
      liner (Reflection XLPE, Smith and Nephew Inc, Memphis, Tenn), and 36 patients in
      group B received a different HXLPE liner (Longevity, Zimmer Inc, Warsaw, Ind).
      Average follow-up was 6.42 years in group A and 7.64 years in group B. The steady
      state head penetration rates were not significantly (P > .05) different between
      the HXPLE groups over the midterm with 0.026 mm/y and 0.025 mm/y in groups A and
      B, respectively.

PMID- 19577898
TI  - Clinical efficacy of mechanical thromboprophylaxis without anticoagulant drugs
      for elective hip surgery in an Asian population.
AB  - To evaluate the clinical efficacy of mechanical thromboprophylaxis after elective
      hip surgery, we reviewed 3016 patients who underwent hip surgery at 5 centers.
      Primary total hip arthroplasty (THA), revision THA, and pelvic or femoral
      osteotomies were performed in 2648, 298, and 70 patients, respectively. Epidural
      anesthesia, intraoperative calf bandage, early mobilization, and intermittent
      pneumatic compression postoperatively with additional use of elastic stockings
      were the basic regimen for thromboprophylaxis. Postoperatively, no cases of fatal
      pulmonary embolism (PE) were encountered. One symptomatic PE and 4 symptomatic
      deep vein thrombosis cases were identified, all of which were successfully
      treated using heparin and warfarin. By 6 months, no deaths had occurred. We
      conclude that mechanical thromboprophylaxis without anticoagulant drugs is safe
      and effective for elective hip surgeries in our patient population.

PMID- 19577897
TI  - Computer-assisted total knee arthroplasty for arthritis with extra-articular
      deformity.
AB  - Forty extra-articular deformities (22 femoral and 18 tibial) in 34 patients (mean
      age, 63.1 years) were studied. Mean coronal extra-articular deformity was 9.3
      degrees ; mean preoperative limb alignment was 166.7 degrees . Three limbs
      underwent simultaneous corrective osteotomy; the rest were treated with intra
      articular correction during computer-assisted total knee arthroplasty (TKA). Mean
      postoperative limb alignment was 179.1 degrees . At a mean follow-up of 26.4
      months, the Knee Society knee score improved from a mean preoperative score of
      49.7 to 90.4 points postoperatively; function score improved from 47.3 to 84.9
      points. Computer-assisted TKA is a useful alternative to conventional TKA for
      knee arthritis with extra-articular deformity where accurate restoration of limb
      alignment may be challenging because of the presence of a deformed tibia or femur
      or in the presence of hardware.

PMID- 19577899
TI  - Hurricane Katrina and youth anxiety: the role of perceived attachment beliefs and
      parenting behaviors.
AB  - This study sought to examine the role of attachment beliefs and parenting
      behaviors on youth's anxious response to disaster by testing a theoretical model
      which posits youths' perceptions of attachment beliefs and parenting behaviors as
      moderators of the relation between pre and post disaster anxiety symptoms.
      Seventy-four youth (ages 6-17 years) and their parents exposed to Hurricane
      Katrina participated in pre and post disaster assessments. Results indicated that
      both youths' pre disaster perceived attachment beliefs (i.e., trust and
      communication) and perceptions of parenting behaviors (i.e., acceptance and firm
      control) moderated the relation between pre and post Katrina anxiety symptoms.
      Exploratory analyses demonstrated no age, gender, or ethnicity differences in
      post Katrina anxiety symptoms. Findings are discussed in terms of how parents may
      influence youths' pre and post disaster anxiety symptoms in the face of natural
      disasters and the implications for intervention.

PMID- 19577900
TI  - Selecting features for BCI control based on a covert spatial attention paradigm.
AB  - Covert attention to spatial locations in the visual field is a relatively new
      control signal for brain-computer interfaces. Previous EEG research has shown
      that trials can be classified by thresholding based on left and right hemisphere
      alpha power in covert spatial attention paradigms. We reexamine the covert
      attention paradigm based on MEG measurements for fifteen subjects. It is shown
      that classification performance can be improved by applying sparse logistic
      regression in order to select a subset of the sensors specific to each subject as
      the basis for classification. Furthermore, insight is gained into how
      classification performance changes as a function of the length of the attention
      period and as a function of the number of trials. Classification performance
      steadily increases as the length of the attention period over which is averaged
      is increased, although this does not necessarily translate into higher bit rates.
      Good classification performance using early components of the attention period
      may be related to evoked response. With regard to the number of used trials,
      classification performance became maximal after 150 samples had been obtained,
      requiring a training time of approximately eleven minutes under the current
      experimental paradigm.

PMID- 19577901
TI  - Adaptive ultrasound imaging of the lumbar spine for guidance of epidural
      anesthesia.
AB  - Ultrasound imaging can help in choosing the needle trajectory for epidural
      anesthesia but anatomical features are not always clear. Spatial compounding can
      emphasize structures; however, features in the beam-steered images are not
      aligned due to varying speeds of sound. A non-rigid registration method, called
      warping, shifts pixels of the beam-steered images to best match the reference
      image. Linear prediction is used to find the warping vectors and decrease
      computational cost. An adaptive median-based combination technique for
      compounding is also investigated. The algorithms are tested on a spine phantom
      and human subjects. The results show a significant improvement in quality when
      using warping with adaptive median-based compounding.

PMID- 19577902
TI  - Use of nasal packs and intranasal septal splints following septoplasty.
AB  - The aim of this study was to compare the efficacy of a trans-septum suturing
      technique with conventional nasal packing and intranasal splints in the classic
      septoplasty operation. The study is a prospective, randomized clinical trial. 114
      patients underwent septoplasty for septal deviation and ensuing nasal
      obstruction. These patients were divided into two groups: packing (using
      intranasal septal splints and antibiotic meshes at the end of the operation) and
      non-packing (using four separate trans-septum through and through horizontal
      mattress sutures without any mesh or intranasal splint insertion). Randomization
      was performed using the four block randomization system. Patients who failed the
      regular follow-up were excluded, and the two groups were compared for
      postoperative bleeding, hematoma, perforation and synechiae. Patients were asked
      to record pain levels using a visual analogue scale. The authors found no
      significant statistical differences between the two groups in the parameters
      studied, but significantly higher pain levels were noted in the patients in the
      packing group. The final results confirmed that patients who underwent
      septoplasty, intranasal packing and septal splint insertion did not benefit more
      than those who had trans-septum through and through suturing.

PMID- 19577904
TI  - Dynamic surface tension of saliva: general relationships and application in
      medical diagnostics.
AB  - Maximum bubble pressure and pendent drop profile analysis tensiometry are used to
      study the dynamic surface tension and rheological characteristics of saliva
      samples taken from volunteers of various sexes and age, and children with caries.
      The tensiometric characteristics of the secretions released by parotid,
      submandibular and sublingual glands are studied, and age-related and sex-related
      changes of some tensiometric characteristics of saliva are found. The differences
      are most essential for the tensiometric characteristics of saliva samples taken
      from caries-free children as compared with those taken from children with caries.
      Thus, the dynamic interfacial tensiometry is very sensitive and capable of
      providing information additional to the biochemical data about the properties of
      saliva, and could be recommended for the development of new diagnostic methods in
      dentistry.

PMID- 19577903
TI  - The antinociceptive properties of reboxetine in acute pain.
AB  - The antinociceptive effects of the selective noradrenaline reuptake inhibitor
      antidepressant reboxetine and its interaction with various opioid and
      noradrenaline receptor subtypes were evaluated. Reboxetine (i.p.) induced a weak
      dose-dependent antinociceptive effect in acute pain, using the hotplate model.
      The reboxetine-induced antinociception was significantly inhibited by the opioid
      receptor antagonists naloxone, nor-BNI, naltrindole and b-FNA, implying a non
      selective role for the opioid receptors in the reboxetine's antinociceptive
      effect. The adrenergic antagonists yohimbine and phentolamine attenuated to some
      extent the reboxetine-induced antinociception, implying a minor adrenergic
      mechanism of antinociception. The addition of opioid or alpha2 agonists, did not
      potentiate the antinociception effect of reboxetine. Thus, it seems that
      reboxetine possesses a weak antinociceptive effect, mediated by non-selective
      opioid receptors and influenced somewhat by noradrenaline alpha2 receptors. These
      results suggest that reboxetine as monotherapy does not have sufficient efficacy
      in the management of acute pain. However, further research is needed in order to
      establish its possible use alone or in combination with other antidepressants or
      analgesics in the amelioration of chronic pain disorders.

PMID- 19577905
TI  - A novel "green" synthesis of starch-capped CdSe nanostructures.
AB  - This paper reports a "green" facile, room temperature, one-pot synthesis of
      starch-capped CdSe nanostructures with an obvious quantum confinement effect via
      a novel non-organometallic method. It is found that by simply tuning the Cd:Se
      molar ratio, dots and elongated particles of high aspect ratio could be prepared
      selectively in the presence of the same ligand concentration without any post
      treatment. Spherical particles were produced at 1:1 ratio, while elongated
      particles were produced at 0.5:1 Cd:Se ratio. The X-ray diffraction (XRD)
      analysis showed that the particles were predominantly of wurtzite structure, with
      sharp diffraction patterns regardless of their size and shapes. We inferred that
      the elongated particles are formed by self-reorganisation occurring via adhesion
      between the spherical nanoparticles as a result of dipole-dipole interactions.

PMID- 19577906
TI  - [Nasal foreign body in infants].
AB  - AIMS: Provide a descriptive analysis of children admitted to a tertiary care
      pediatric emergency department (PED) for a nasal foreign body (NFB) and describe
      the current knowledge and management of such accidents. MATERIAL AND METHODS: A
      retrospective study was conducted from January 2003 to May 2008, including all
      patients aged less than 15 years admitted for a NFB. The data collected were age,
      sex, geographic origin, time and day of admission, duration in PED, duration of
      NFB insertion, nostril location, symptoms and clinical signs, prehospital
      extraction attempts, facial x-ray, extraction mode, referral to an ENT
      specialist, progression, and complications. For statistical analysis, the data
      were entered in Microsoft Excel spreadsheets. The data were analyzed with
      StatView 5.1 (SAS Institute) and EpiInfo 6.04fr (VF, ENSP Epiconcept). In the
      descriptive analysis, the data are presented as mean values with standard
      deviation, median with extreme values or with 95% confidence intervals where
      appropriate, unless otherwise indicated. To compare qualitative variables, a
      chi(2) test (Mantel-Haenszel) was used and the two-tailed Fisher exact test if
      the expected value was 5 or less. Statistical significance was set at p<0.05.
      RESULTS: A total of 388 patients were included (393 NFB). The annual mean number
      of cases was 68. The annual distribution showed a higher number in January,
      March, April, and October following Christmas, Easter and Halloween celebrations,
      totaling 40% of all NFB admissions. The sex-ratio was 0.95. Children aged less
      than 4 years accounted for 71% of the studied population. The mean age was 3.5+/
      1.6 years (range, 1.4-13 years). The majority of accidents occurred at home
      (95%). The length of time spent in the PED was 78+/-57 min. The NFB duration of
      insertion was unknown in one-quarter of cases, present for less than 4 h in 65%
      of cases. No symptoms were described in most cases (88%). When symptoms were
      described, bleeding, pain or nasal discomfort, and foul nasal odor were the
      principal symptoms. The right nostril was the predominant location (60%). This
      difference tended to disappear in the group of children aged less than 4 years.
      Five children had bilateral NFB. Nonorganic compounds accounted for 80% of the
      NFB: plastic beads or balls (39%), plastic or toy parts (20%), stones or pebbles
      (11%), and paper (6%). The extraction was instrumental in 82% of cases, and 26%
      of patients were referred to an ENT specialist when PED attempts were
      unsuccessful. One child needed hospitalization for extraction under general
      anesthesia of two beads located deep in the same nostril. No complication
      occurred. Five children had repeated accidents within an average delay of 6
      months. CONCLUSION: Often benign, this frequent accident can be serious in case
      of batteries or neodymium magnet insertion: the extraction becomes an emergency
      because of risks of nasal mucosa necrosis and/or nasal septum perforation. In
      other cases, positive pressure techniques (the parent's kiss or its variants)
      could be tried first in the emergency department or at home at the time of a call
      to emergency services before a medical visit.

PMID- 19577907
TI  - [How to assess the correct position of intraosseous access? A case report].

PMID- 19577908
TI  - [Factors related to extubation failure in premature infants less than 32 weeks of
      gestation].
AB  - Even though ventilatory support for preterm infants has improved over the past
      few decades, about 30% of intubated preterm infants fail an extubation attempt.
      There are still no simple standards to determine the optimal extubation time for
      those infants. OBJECTIVE: To identify factors related to extubation success or
      failure in preterm infants less than 32 weeks of gestation (WG). POPULATION AND
      METHODS: Retrospective study including 162 newborns less than 32 WG, requiring
      mechanical ventilation within the first 24h of life. Successful extubation was
      defined as no need for reintubation for any reason at least 7 days after the
      first extubation attempt. RESULTS: Forty-one infants failed extubation (25.3%);
      149 infants (92%) had mechanical ventilation in their first 30min of life. These
      infants had a lower gestational age (p<0.001) and a lower birth weight (p=0.003).
      They required a higher FiO(2) (p<0.001) and maximum inspiratory pressure
      (p=0.002). The infants who failed extubation had a lower pH (p=0.001) and
      hematocrit (p=0.032), and a higher PCO(2) (p=0.003). CONCLUSION: As previously
      described, a low gestational age is a major factor predicting the extubation
      failure. However, our data suggests that ventilator settings and blood gas should
      also be considered when attempting extubation, following written guidelines.

PMID- 19577909
TI  - [Acute poststreptoccocal chorea: an atypical postoperative reaction following
      cardiac surgery for mitral valvulopathy].
AB  - We report on a 12-year-old patient from Congo who presented acute chorea
      following cardiac surgery for poststreptococcal mitral valvulopathy. She showed
      severe and asymmetrical chorea, associated with motor impersistence and
      agitation. Biological investigations disclosed inflammatory signs and brain MRI
      was normal. Due to the negative results of the biological and morphological
      investigations, the diagnosis of Sydenham chorea was suspected. High doses of
      oral steroids resulted in a dramatic improvement of the chorea as well as the
      behavior disturbance within 1 month. Sydenham chorea is not an unusual
      complication of rheumatic fever. Usually, patients develop chorea a few weeks
      after beta-hemolytic streptococcal pharyngitis. Details on its pathophysiology
      remain to be determined. Our case highlights its possible onset in the
      postoperative period if alternative etiologies of infantile chorea have been
      excluded.

PMID- 19577910
TI  - Identification of two vicinal operons for the degradation of 2
      aminobenzenesulfonate encoded on plasmid pSAH in Alcaligenes sp. strain O-1.
AB  - Alcaligenes sp. strain O-1 inducibly deaminates 2-aminobenzenesulfonate (ABS) via
      dioxygenation to 3-sulfocatechol, which is desulfonated during meta ring-cleavage
      to yield 2-hydroxymuconate. This intermediate is transformed through the
      oxalocrotonate-branch of the sulfocatechol meta-pathway (Scm). The complete
      pathway is encoded on the 180-kb plasmid pSAH, 20kb of which was sequenced.
      Twenty open reading frames (ORFs) were detected. Two clusters (abs and scm) with
      degradative genes were surrounded by several transposon-related ORFs. The six
      genes of the abs cluster were shown to be co-transcribed, and contained the genes
      for two characterised subunits of the oxygenase component of the ABS-dioxygenase
      system, and genes putatively encoding ABS-transport functions with similarities
      to (a) an ABC-type transporter system and (b) a putative major facilitator
      superfamily transporter. No gene encoding the reductase for the oxygenase system
      was present in the abs gene cluster, but a candidate gene was found in the scm
      cluster. The seven-gene scm cluster was also transcribed as single polycistronic
      message. Functions could be attributed to the gene products, but one enzyme,
      which was shown to be present, 2-hydroxymuconate isomerase, was not encoded in
      the scm cluster. No transcriptional regulator was found. This genetic information
      on the degradation of ABS in strain O-1 provides another example of both split
      operons and dispersed pathway genes.

PMID- 19577911
TI  - A novel mosquitocidal Bacillus thuringiensis strain LLP29 isolated from the
      phylloplane of Magnolia denudata.
AB  - Eleven Bacillus thuringiensis isolates were recovered from phylloplanes of
      Magnolia denudata, a specific source of new strains of B. thuringiensis. Among
      these, a new strain, LLP29, was found to be most toxic to mosquitoes based on the
      results of preliminary toxicity analysis. Phase contrast microscopy,
      mosquitocidal activity, polymerase chain reaction (PCR) analysis and parasporal
      inclusion were performed to learn more about the characteristics of this novel
      mosquitocidal isolate. The LC(50) values of LLP29 against Aedes albopictus and
      Culex quinquefasciatus were 0.33 and 0.04 ng of protein/ml, respectively. The
      cyt1 gene, which encodes the Cyt protein that is toxic to mosquitoes, was
      subsequently detected, cloned, sequenced and expressed in acrystalliferous Bt
      HD73 Cry(-). The results indicated that it might be a member of the cyt1Aa gene
      group. The novel strain LLP29 appears to be a new subspecies of B. thuringiensis
      and should prove useful in the control of mosquitoes and mosquito-borne diseases.

PMID- 19577912
TI  - The protective efficacy of magnolol in hind limb ischemia-reperfusion injury.
AB  - We investigated the protective effects of magnolol, an active antioxidant and
      free radical scavenger extracted from Magnolia officinalis, in a hind limb
      ischemic-reperfusion animal model. Adult male Sprague-Dawley rats were subjected
      to hind limb ischemic insult for 2 hours and were intravenously treated with
      magnolol at 0.01 mg/kg (n=8), 0.3 mg/kg (n=8) mg/kg or 1 mg/kg (n=8) mg/kg, or
      vehicle (n=8). At 24 h post-insult, the levels of nitrite/nitrate (NOX),
      malondialdehyde (MDA) and myeloperoxidase (MPO), as well as the degree of muscle
      damage, were assessed. Relative to controls, animals treated with magnolol (0.3
      and 1 mg/kg) had attenuated muscular inflammation, edema and damage. Magnolol
      (0.3-1 mg/kg) also effectively reduced postischemic rises in the MDA, NOx and MPO
      levels (p<0.05, respectively). Magnolol administrated at 0.01 mg/kg, however,
      failed to protect against the ischemic-perfusion limb injury. In addition,
      magnolol (0.01-1 mg/kg) did not affect local muscular blood reperfusion or other
      physiological parameters, including hematocrit, glucose, arterial blood gases and
      mean arterial blood pressure. Thus, intravenous administration with magnolol at
      0.3-1 mg/kg protects against ischemic limb damage in rats. This cytoprotection
      may be attributed to its antioxidant, anti-nitrosative and anti-inflammatory
      actions.

PMID- 19577913
TI  - Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B
      irradiation-induced skin damage in melanin-possessing hairless mice.
AB  - Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a
      dietary pigment and spice, and has been traditionally used for the treatment of
      inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese
      medicine. Although the topical application or oral administration of turmeric is
      used to improve skin trouble, there is no evidence to support this effect. The
      aim of this study was to clarify whether turmeric prevents chronic ultraviolet B
      (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on
      skin damage including changes in skin thickness and elasticity, pigmentation and
      wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin
      possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily)
      prevented an increase in skin thickness and a reduction in skin elasticity
      induced by chronic UVB exposure. It also prevented the formation of wrinkles and
      melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and
      length of skin blood vessels and in the expression of matrix metalloproteinase-2
      (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the
      inhibition of increases in MMP-2 expression caused by chronic irradiation.

PMID- 19577914
TI  - Reevaluation of the DHA requirement for the premature infant.
AB  - The long-chain polyunsaturated fatty acid (LC-PUFA) intake in preterm infants is
      crucial for normal central nervous system development and has the potential for
      long-lasting effects that extend beyond the period of dietary insufficiency.
      While much attention has focused on improving their nutritional intake, many
      premature infants do not receive an adequate DHA supply. We demonstrate that
      enterally fed premature infants exhibit daily DHA deficit of 20mg/kg.d,
      representing 44% of the DHA that should have been accumulated. Furthermore, the
      DHA content of human milk and current preterm formulas cannot compensate for an
      early DHA deficit which may occur during the first month of life. We recommend
      breast-feeding, which supplies preformed LC-PUFA, as the preferred method of
      feeding for preterm infants. However, to fulfill the specific DHA requirement of
      these infants, we recommend increasing the DHA content of human milk either by
      providing the mothers with a DHA supplement or by adding DHA directly to the
      milk. Increasing the DHA content above 1% total fatty acids appears to be safe
      and may enhance neurological development particularly that of infants with a
      birth weight below 1250 g. We estimate that human milk and preterm formula should
      contain approximately 1.5% of fatty acid as DHA to prevent the appearance of a
      DHA deficit and to compensate for the early DHA deficit.

PMID- 19577916
TI  - Production of lightweight aggregate from industrial waste and carbon dioxide.
AB  - The concomitant recycling of waste and carbon dioxide emissions is the subject of
      developing technology designed to close the industrial process loop and
      facilitate the bulk-re-use of waste in, for example, construction. The present
      work discusses a treatment step that employs accelerated carbonation to convert
      gaseous carbon dioxide into solid calcium carbonate through a reaction with
      industrial thermal residues. Treatment by accelerated carbonation enabled a
      synthetic aggregate to be made from thermal residues and waste quarry fines. The
      aggregates produced had a bulk density below 1000 kg/m(3) and a high water
      absorption capacity. Aggregate crushing strengths were between 30% and 90%
      stronger than the proprietary lightweight expanded clay aggregate available in
      the UK. Cast concrete blocks containing the carbonated aggregate achieve
      compressive strengths of 24 MPa, making them suitable for use with concrete
      exposed to non-aggressive service environments. The energy intensive firing and
      sintering processes traditionally required to produce lightweight aggregates can
      now be augmented by a cold-bonding, low energy method that contributes to the
      reduction of green house gases to the atmosphere.

PMID- 19577917
TI  - Rapid and sensitive detection of microcystin by immunosensor based on nuclear
      magnetic resonance.
AB  - A stable and sensitive toxin residues immunosensor based on the relaxation of
      magnetic nanoparticles was developed. The method was performed in one reaction
      and offered sensitive, fast detection of target toxin residues in water. The
      target analyte, microcystin-LR (MC-LR) in Tai lake water, competed with the
      antigens on the surface of the magnetic nanoparticles and then influenced the
      formation of aggregates of the magnetic nanoparticles. Accordingly, the magnetic
      relaxation time of the magnetic nanoparticles was changed under the effect of the
      target analyte. The calibration curve was deduced at different concentrations of
      the target analyte. The limit of detection (LOD) of MC-LR was 0.6 ng g(-1) and
      the detection range was 1-18 ng g(-1). Another important feature of the developed
      method was the easy operation: only two steps were needed (1) to mix the magnetic
      nanoparticle solution with the sample solution and (2) read the results through
      the instrument. Therefore, the developed method may be a useful tool for toxin
      residues sensing and may find widespread applications.

PMID- 19577915
TI  - Vps-C complexes: gatekeepers of endolysosomal traffic.
AB  - Genetic studies in yeast, plants, insects, and mammals have identified four
      universally conserved proteins, together called Vps Class C, that are essential
      for late endosome and lysosome assembly and for numerous endolysosomal
      trafficking pathways, including the terminal stages of autophagy. Two Vps-C
      complexes, HOPS and CORVET, incorporate diverse biochemical functions: they
      tether membranes, stimulate Rab nucleotide exchange, guide SNARE assembly to
      drive membrane fusion, and possibly act as ubiquitin ligases. Recent studies
      offer new insight into the complex relationships between Vps-C complexes and
      their cognate Rab small GTP-binding (G-)proteins at endosomes and lysosomes.
      Accumulating evidence supports the view that Vps-C complexes implement a
      regulatory logic that governs endomembrane identity and dynamics.

PMID- 19577918
TI  - Graphitized macroporous carbon microarray with hierarchical mesopores as host for
      the fabrication of electrochemical biosensor.
AB  - A novel graphitized ordered macroporous carbon (GMC, pore size approximately 380
      nm) with hierarchical mesopores (2-30 nm) and high graphitization degree was
      prepared by nickel-catalyzed graphitization of polystyrene arrays. The obtained
      GMC possessed high specific surface area, large pore volume, and good electrical
      conductivity, which was explored for the enzyme entrapment and biosensor
      fabrication by a facile method. With advantages of novel nanostructure and good
      electrical conductivity, direct electrochemistry of hemoglobin (a model protein)
      was observed on the GMC-based biocomposite with a formal potential of -0.36 V
      (vs. Ag/AgCl) and an apparent heterogeneous electron transfer rate constant
      (k(s)) of 1.2 s(-1) in pH 7.0 buffer. Comparative studies revealed that GMC
      offered significant advantages over carbon nanotubes (CNTs) in facilitating
      direct electron transfer of entrapped Hb. The fabricated biosensor exhibited good
      sensitivity (101.6 mA cm(-2) M(-1)) and reproducibility, wide linear range (1-267
      microM), low detection limit (0.1 microM), and good long-term stability for
      H(2)O(2) detection. GMC proved to be a promising matrix for enzyme entrapment and
      biosensor fabrication, and may find wide potential applications in biomedical
      detection and environmental analyses.

PMID- 19577920
TI  - A simple method to determine bioethanol content in gasoline using two-step
      extraction and liquid scintillation counting.
AB  - A simple method for determining bioethanol content in gasoline containing
      bioethanol (denoted as E-gasoline in this study) is urgently required. Liquid
      scintillation counting (LSC) was employed based on the principle that (14)C
      exists in bioethanol but not in synthetic ethanol. Bioethanol was extracted in
      two steps by water from E-gasoline containing 3% (E3) or 10% (E10) bioethanol.
      The (14)C radioactivity was measured by LSC and converted to the amount of
      bioethanol. The bioethanol content in E-gasoline was determined precisely from
      the partition coefficient in the extraction and the amount of bioethanol in the
      water phases: 2.98+/-0.10% for E3 and 10.0+/-0.1% for E10 (means+/-SD; n=3). It
      appears that this method can be used to determine bioethanol content in E
      gasoline quickly and easily.

PMID- 19577919
TI  - Mass spectrometry in the analysis of N-linked and O-linked glycans.
AB  - Mass spectrometry (MS) continues to play a vital role in defining the structures
      of N-glycans and O-glycans in glycoproteins via glycomic and glycoproteomic
      methodologies. The former seeks to define the total N-glycan and/or O-glycan
      repertoire in a biological sample whilst the latter is concerned with the
      analysis of glycopeptides. Recent technical developments have included
      improvements in tandem mass spectrometry (MS/MS and MS(n)) sequencing
      methodologies, more sensitive methods for analysing sulfated and polysialylated
      glycans and better procedures for defining the sites of O-glycosylation. New
      tools have been introduced to assist data handling and publicly accessible
      databases are being populated with glycomics data. Progress is exemplified by
      recent research in the fields of glycoimmunology, reproductive glycobiology, stem
      cells, bacterial glycosylation and non-mucin O-glycosylation.

PMID- 19577921
TI  - Generation and identification of DNA sequence flanking T-DNA integration site of
      Trichoderma atroviride mutants with high dichlorvos-degrading capacity.
AB  - A protocol for efficient Agrobacterium tumefaciens-mediated transformation (ATMT)
      of biocontrol fungus Trichoderma atroviride strain T23 was developed to construct
      mutants with improved dichlorvos-degradation ability. A transformation frequency
      of 5x10(-6) was achieved. Among 110 genetically stable T-DNA transformants of T.
      atroviride T23, two transformants, AMT-12 and AMT-28, confirmed by Southern blot
      analysis to have single-copy inserts of T-DNA, showed an increase in dichlorvos
      degradation ability of more than 10% compared to that of the wild type, exhibited
      similar tolerance to the pesticide, but lower spore formation ability. Five
      transformants exhibited a reduction in degradation of more than 70%, exhibited
      wild-type spore formation, and tolerated up to 800 microg/mL of dichlorvos. The
      left-flanking sequence of the insertion site in AMT-12 was cloned as a 1845-bp
      fragment and shown to have 89% identity to the DNA from T. atroviride IMI 206040;
      however, the involvement of this DNA in dichlorvos degradation remains still to
      be determined. This study can promote both a more efficient isolation of DNA
      sequence flanking T-DNA integration site in T. atroviride mutants and a more
      rational utilization of these transformants in dichlorvos degradation.

PMID- 19577922
TI  - Anaerobic digestion foaming causes--a review.
AB  - Anaerobic digestion foaming has been encountered in several sewage treatment
      plants in the UK. Foaming has raised major concerns for the water companies due
      to significant impacts on process efficiency and operational costs. Several
      foaming causes have been identified over the past few years by researchers.
      However, the supporting experimental information is limited and in some cases
      absent. The present report aims to provide a detailed review of the current
      anaerobic digestion foaming problem and to identify gaps in knowledge regarding
      the theory of foam formation in anaerobic digesters.

PMID- 19577923
TI  - Maximum use of resources present in domestic "used water".
AB  - Environmental protection and the sustainable management of natural resources
      stand at the foreground of economic and technological activities worldwide.
      Current sewage technologies, however, deal with diluted wastes and do not focus
      on recovery and are therefore not sustainable. Here, the most promising methods
      available for the recovery of nutrients (nitrogen, phosphorus), organic material
      and energy from "used waters" are examined both at the decentralised and
      centralised level. Novel approaches for water processing, not implementing
      aerobic biological treatment as a core technology, are conceived and critically
      evaluated regarding efficiency, diffuse emissions and requisite costs. By
      implementing up-concentration of dilute wastewaters, the concentrated stream
      becomes suitable for the waste-to-energy strategy. The approach of up
      concentration of municipal effluent at arrival at the water treatment plant
      followed by anaerobic digestion of organics and maximal reuse of the mineral
      nutrients and water is estimated to have a total cost of the order 0.9
      euros/m(3); the latter is comparable to that of conventional aerobic treatment
      technologies which has little or no reuse. It is argued that in view of the fact
      that recovered nutrients will become of increasing economic and ecological value,
      this new conceptual design for the treatment of "used water" will become feasible
      in the next decade.

PMID- 19577924
TI  - Process of simultaneous hydrogen sulfide removal from biogas and nitrogen removal
      from swine wastewater.
AB  - The feasibility of a new flowchart describing simultaneous hydrogen sulfide
      removal from biogas and nitrogen removal from wastewater was investigated. It
      took 30 days for the reactor inoculated with aerobic sludge to attain a removal
      rate of 60% for H(2)S and NO(x)-N simultaneously. It took 34 and 48 days to
      attain the same removal rate for the reactor without inoculated sludge and the
      reactor inoculated with anaerobic sludge respectively. The reactor without
      inoculated sludge still operated successfully, despite requiring a slightly
      longer startup time. The packing material was capable of enhancing the removal
      efficiency of reactors. Based on the concentration of NO(x)-N and H(2)S in the
      effluent, the loading rate and the ability of the system to resist shock loading,
      the performance of the reactor filled with hollow plastic balls was greater than
      that of the reactor filled with elastic packing and the reactor filled with Pall
      rings.

PMID- 19577925
TI  - Production of lactic acid from paper sludge using acid-tolerant, thermophilic
      Bacillus coagulan strains.
AB  - Production of lactic acid from paper sludge was studied using thermophilic
      Bacillus coagulan strains 36D1 and P4-102B. More than 80% of lactic acid yield
      and more than 87% of cellulose conversion were achieved using both strains
      without any pH control due to the buffering effect of CaCO(3) in paper sludge.
      The addition of CaCO(3) as the buffering reagent in rich medium increased lactic
      acid yield but had little effect on cellulose conversion; when lean medium was
      utilized, the addition of CaCO(3) had little effect on either cellulose
      conversion or lactic acid yield. Lowering the fermentation temperature lowered
      lactic acid yield but increased cellulose conversion. Semi-continuous
      simultaneous saccharification and co-fermentation (SSCF) using medium containing
      100 g/L cellulose equivalent paper sludge without pH control was carried out in
      serum bottles for up to 1000 h. When rich medium was utilized, the average lactic
      acid concentrations in steady state for strains 36D1 and P4-102B were 92 g/L and
      91.7 g/L, respectively, and lactic acid yields were 77% and 78%. The average
      lactic acid concentrations produced using semi-continuous SSCF with lean medium
      were 77.5 g/L and 77.0 g/L for strains 36D1 and P4-102B, respectively, and lactic
      acid yields were 72% and 75%. The productivities at steady state were 0.96 g/L/h
      and 0.82 g/L/h for both strains in rich medium and lean medium, respectively. Our
      data support that B. coagulan strains 36D1 and P4-102B are promising for
      converting paper sludge to lactic acid via SSCF.

PMID- 19577926
TI  - The effect of ozone on tannery wastewater biological treatment at demonstrative
      scale.
AB  - This paper reports the results obtained during an investigation aimed at
      transferring to the demonstrative scale an aerobic granular biomass system (SBBGR
      -Sequencing Batch Biofilter Granular Reactor) integrated with ozonation for the
      efficient treatment of tannery wastewater. The results show that the integrated
      process was able to achieve high removal efficiencies for COD, TSS, TKN,
      surfactants and colour with residual concentrations much lower than the current
      discharge limits. Furthermore, the process was characterised by a very low sludge
      production (i.e., 0.1 kg dry sludge/m(3) of treated wastewater) with interesting
      repercussions on treatment costs (about 1 euro per m(3) of wastewater).

PMID- 19577927
TI  - Infection strategies of filamentous microbes described with the Gene Ontology.
AB  - Filamentous microbes that form highly developed symbiotic associations (ranging
      from pathogenesis to mutualism) with their hosts include fungi, oomycetes and
      actinomycete bacteria. These organisms share many common features in growth,
      development and infection and have evolved similar strategies for neutralizing
      host defense responses to establish symbioses. Recent advances in sequencing
      technologies have led to a remarkable increase in the number of sequenced genomes
      of filamentous organisms. Analysis of the available genomes has provided useful
      information about genes that might be important for host infection and
      colonization. However, because many functional similarities among these organisms
      have arisen by convergent evolution, sequence-based genomic comparisons will miss
      many genes that are functionally analogous. In the absence of sequence
      similarity, annotating genes with standardized terms from the Gene Ontology (GO)
      can facilitate functional comparisons. Here, we review common strategies employed
      by filamentous organisms during colonization of their hosts, with reference to GO
      terms that best describe the processes involved.

PMID- 19577929
TI  - Viewing the microbial world through the lens of the Gene Ontology.

PMID- 19577930
TI  - Efficacy of surgery and type of fusion in patients with degenerative lumbar
      spinal stenosis.
AB  - Degenerative lumbar spinal stenosis (DLSS) can be treated by several surgical
      procedures. However, the choice of procedure and use of instrumentation remain
      controversial. In this retrospective study of 81 patients with DLSS, 43 patients
      received decompression and posterolateral fusion without instrumentation, and the
      surgery for 38 patients was supplemented with posterior transpedicular screw
      fixation. Both surgeon-based (Fischgrund criteria) and patient-based (Medical
      Outcome Trust Short-Form 36 [SF-36] questionnaire) standards were used to assess
      the clinical outcomes. An excellent to good result was achieved in 71.6% of
      patients and there was no significant difference 6.2 years later between groups
      with or without instrumentation (Z=0.0358, p>0.05). SF-36 data revealed
      significant postoperative improvement (p<0.01), and there was no significant
      difference between the two groups (t=1.67, p>0.05). Successful fusion occurred in
      87% of patients with instrumentation versus 67% of the patients without
      instrumentation (chi(2)=4.23, p<0.05). Thus, surgical treatment of DLSS generally
      results in satisfactory outcomes. Transpedicular screw fixation may not improve
      clinical outcomes and the use of posterior instrumentation should be adopted
      cautiously.

PMID- 19577928
TI  - Gene Ontology and the annotation of pathogen genomes: the case of Candida
      albicans.
AB  - The Gene Ontology (GO) is a structured controlled vocabulary developed to
      describe the roles and locations of gene products in a consistent manner and in a
      way that can be shared across organisms. The unicellular fungus Candida albicans
      is similar in many ways to the model organism Saccharomyces cerevisiae but, as
      both a commensal and a pathogen of humans, differs greatly in its lifestyle. With
      an expanding at-risk population of immunosuppressed patients, increased use of
      invasive medical procedures, the increasing prevalence of drug resistance and the
      emergence of additional Candida species as serious pathogens, it has never been
      more crucial to improve our understanding of Candida biology to guide the
      development of better treatments. In this brief review, we examine the importance
      of GO in the annotation of C. albicans gene products, with a focus on those
      involved in pathogenesis. We also discuss how sequence information combined with
      GO facilitates the transfer of knowledge across related species and the
      challenges and opportunities that such an approach presents.

PMID- 19577931
TI  - N-terminal-prolonged vinyl ester-based peptides as selective proteasome beta1
      subunit inhibitors.
AB  - The synthesis and biological properties of vinyl ester peptide-based molecules
      bearing linear N-terminal amino acids are reported. Compounds were tested in
      vitro for their capacity to inhibit the chymotryptic-, tryptic-like, and post
      acidic activities of the proteasome. Some analogues showed selective inhibition
      of post-acidic (PGPH) activity, which is attributed to the beta1 subunit.
      Interestingly, active compounds demonstrated higher inhibitory activity toward
      'standard' proteasomes than toward immunoproteasomes. The inhibitory potency was
      found to be related to the amino acidic sequence and to the length of the N
      terminal residues. The new inhibitors demonstrated resistance to plasmatic
      proteases and a good capacity to permeate the cell membrane.

PMID- 19577932
TI  - 'Novel alkyl side chain sulfone 1alpha,25-dihydroxyvitamin D3 analogs: a
      comparison of in vitro antiproliferative activities and in vivo calcemic
      activities'.
AB  - The replacement of a t-butyl group with a trifluoromethyl group has profound
      effects on the biological profile of 1alpha,25-dihydroxyvitamin D(3) sulfone
      analogs. Investigation of whether the improved biological activities are due to
      steric and electronic factors of the trifluoromethyl group led to the design,
      synthesis and biological evaluation of two analogous alkyl sulfone molecules,
      methyl sulfone (AU-16-ene-25-SO(2)-CH(3)) and isopropyl sulfone (AU-16-ene-25
      SO(2)-i-Pr). These alkyl sulfones are sterically comparable to, but
      electronically very different from a trifluoromethyl group. The syntheses,
      antiproliferative activities and calcemic activities of these new alkyl sulfones
      are presented herein. In comparing the in vitro antiproliferative profiles of the
      new alkyl sulfone 1alpha,25-dihydroxyvitamin D(3) analogs with the
      trifluoromethylsulfone and an analogous t-butyl sulfone, the activities increase
      in the following order: CH(3) < t-Bu approximately = i-Pr < CF(3). In contrast to
      the calcemic t-butyl sulfone, the novel alkyl sulfones and trifluoromethyl
      sulfone display desirable low calcemic levels.

PMID- 19577933
TI  - Discriminatory synergistic effect of Trp-substitutions in superagonist
      [(Arg/Lys)(14), (Arg/Lys)(15)]nociceptin on ORL1 receptor binding and activation.
AB  - ORL1 is an endogenous G protein-coupled receptor for neuropeptide nociceptin.
      [(R/K)(14), (R/K)(15)]nociceptin is a superagonist that strongly activates the
      ORL1 receptor. We have previously found that substituting with Trp can reproduce
      the potentiation induced by Arg or Lys at position 14. In the present study, in
      order to ensure the effect of Trp-substitution on the activities of [(R/K)(14),
      (R/K)(15)]nociceptin, we synthesized [W(14), (R/K)(15)]nociceptin and [(R/K)(14),
      W(15)]nociceptin. [W(14), (R/K)(15)]nociceptin was found to exhibit threefold
      higher binding activity and 10-fold greater potency in a functional
      [(35)S]GTPgammaS functional assay as compared to wild-type nociceptin. However,
      when only Trp was placed in position 15, the resulting analogues, [(R/K)(14),
      W(15)]nociceptin, showed only a moderate enhancement of binding and biological
      activity (2-3 fold in both). These results indicate that the placement of Trp at
      position 14, unlike at position 15, enhances in a synergistic fashion the
      interaction of nociceptin with the ORL1 receptor. The results indicate that
      specific interactions feasible for Arg/Lys and Trp in common must be there for
      aromatic residues in ORL1, thus forming a cation/pi interaction or pi/pi
      hydrophobic interaction. The necessity for a favorable electrostatic interaction
      appears strict in position 15.

PMID- 19577934
TI  - Molecular characterization of an ethephon-induced Hsp70 involved in high and low
      temperature responses in Hevea brasiliensis.
AB  - Hsp70s have been shown to play important roles in helping cells to cope with
      adverse environments, especially in response to temperature. In this study a
      novel ethephon-induced Hsp gene, designated as HbHsp70, was isolated from Hevea
      brasiliensis. The HbHsp70 cDNA contained a 1965 bp open reading frame encoding
      655 amino acids. The deduced HbHsp70 protein showed high identities to Hsp70s
      from other plants. Expression studies revealed more significant accumulation of
      HbHsp70 transcripts in leaves and stems than in roots, barks and latex. The
      transcription of HbHsp70 was induced by ethephon, heat treatment and low
      temperature stress, whereas jasmonic acid had little effects. Recombinant HbHsp70
      was expressed in Escherichia coli and purified by Ni-NTA affinity chromatography.
      Measuring the light scattering of luciferase (Luc) revealed that HbHsp70 prevents
      the aggregation of luc during high-temperature stress. In vitro experiments
      showed that HbHsp70 had protective functions not only against heat stress but
      also against chilling stress. All these data suggest that HbHsp70 may play roles
      in responses to heat shock and low temperature in H. brasiliensis.

PMID- 19577935
TI  - Top-down proteomics reveals novel protein forms expressed in Methanosarcina
      acetivorans.
AB  - Using both automated nanospray and online liquid chromatography mass spectrometry
      LC-MS strategies, 99 proteins have been newly identified by top-down tandem mass
      spectrometry (MS/MS) in Methanosarcina acetivorans, the methanogen with the
      largest known genome [5.7 mega base pairs (Mb)] for an Archaeon. Because top-down
      MS/MS was used, 15 proteins were detected with mispredicted start sites along
      with an additional five from small open reading frames (SORFs). Beyond
      characterization of these more common discrepancies in genome annotation, one
      SORF resulted from a rare start codon (AUA) as the initiation site for
      translation of this protein. Also, a methylation on a 30S ribosomal protein
      (MA1259) was localized to Pro59-Val69, contrasting sharply from its homologue in
      Escherichia coli (rp S12) known to harbor an unusual beta-thiomethylated aspartic
      acid residue.

PMID- 19577937
TI  - Centro-median stimulation yields additional seizure frequency and attention
      improvement in patients previously submitted to callosotomy.
AB  - RATIONALE: Deep brain stimulation (DBS) has been increasingly used in the
      treatment of refractory epilepsy over the last decade. We report on the outcome
      after thalamic centro-median (CM) DBS in patients with generalized epilepsy who
      had been previously treated with extended callosal section. METHODS: Four
      consecutive patients with generalized epilepsy who were previously submitted to
      callosal section and had at least 1 year of follow-up after deep brain
      implantation were studied. Age ranged from 19 to 44 years. All patients were
      submitted to bilateral CM thalamic DBS. Post-operative CT scans documented the
      electrode position in all patients. All patients had pre- and post-stimulation
      prolonged interictal scalp EEG recordings, including spike counts. Attention
      level was evaluated by means of the SNAP-IV questionnaire. The pre-implantation
      anti-epileptic drug regimen was maintained post-operatively in all patients.
      RESULTS: Post-operative CT documented that all electrodes were correctly located.
      There was no morbidity or mortality. Seizure frequency reduction ranging from 65
      to 95% and increased attention level was seen in all patients. Interictal spiking
      frequency was reduced from 25 to 95%, but their morphology remained the same.
      There was re-synchronization of interictal discharges during slow-wave sleep in 2
      patients. CONCLUSION: All patients benefit from the procedure. The CM seems to
      play a role in modulating the epileptic discharges and attention in these
      patients. On the other hand, it is not the generator of the epileptic abnormality
      and appeared not to be involved in non-REM sleep-related interictal spiking
      modulation.

PMID- 19577936
TI  - Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus
      independent of weight changes.
AB  - BACKGROUND: Pioglitazone (Pio) treatment induces weight gain in Type 2 diabetes
      mellitus (T2DM), which could worsen hepatic lipid accumulation, and alter
      adiponectin and high-sensitivity C-reactive protein (hs-CRP). OBJECTIVE: To
      compare changes in hepatic lipid, serum adiponectin and hs-CRP in diabetics
      treated with Pio (with and without weight gain) against metformin (Met)
      treatment, which produces weight loss. DESIGN: Fifty-one men and women with T2DM,
      naive to thiazolidinediones, entered a 16-week, open-label, parallel arm study,
      where participants were randomized to one of three groups: (1) Pio plus the
      American Diabetes Association diet (Pio+ADA); (2) Pio plus a portion control
      weight loss diet (Pio+PC), or (3) metformin plus ADA diet (Met+ADA). METHODS:
      Hepatic lipid was assessed with abdominal computed tomography (CT) and the serum
      adiponectin and hs-CRP by enzyme-linked immunosorbent assay at baseline and study
      end. RESULTS: Forty-eight subjects completed the study. The Pio+ADA group gained
      (mean+/-S.E.M.) 2.15+/-1.09 kg, while Pio+PC and Met+ADA group lost -2.59+/-1.25
      and -3.21+/-0.7 kg, respectively. Pio-treated groups (Pio+ADA and Pio+PC)
      significantly decreased hepatic fat as indicated by increased liver density on CT
      scan [10.1+/-2.4: 11.4+/-1.0 Hounsfield units (HU)], compared with Met+ADA group
      (-2.4+/-3.1 HU). The Pio groups demonstrated significantly increased serum
      adiponectin, (8.6+/-1.5; 7.4+/-1.6 microg/ml) independent of weight change,
      compared to Met+ADA (-0.14+/-0.6 microgm/ml) group which lost weight. Serum hs
      CRP decreased in groups showing weight loss (Pio+PC, -3.1+/-1.7 mg/l; Met+ADA, 
      1.5+/-1.2 mg/l) compared to Pio+ADA (1.8+/-3.0 mg/l) group that gained weight.
      CONCLUSIONS: Pio treatment in T2DM significantly reduced hepatic lipid and
      increased adiponectin independent of weight change, while decreasing hs-CRP with
      weight loss.

PMID- 19577938
TI  - Reference values for quantitative ultrasonography (QUS) of radius and tibia in
      healthy greek pediatric population: clinical correlations.
AB  - The aim of this study was to provide reference standards for measurements of
      quantitative ultrasonography (QUS) of radius and tibia in normative Greek
      pediatric population. Analysis was performed in 1549 healthy subjects (814 girls
      and 735 boys) with a mean decimal age of 11.41+/-3.52 yr (range: 3.78-18.33 yr).
      Results showed a gradual increase of absolute values of radial and tibial speed
      of sound (SOS), with aging and with pubertal progressing, in both girls and boys.
      Gender comparison showed significantly increased SOS values measured both at
      radius and at tibia in girls more than 13 yr of age compared with aged-matched
      boys. Significant but mild correlation was noted between standard deviation
      scores (SDS) of SOS at radius and at tibia (r = 0.259, p < 0.001). Additionally,
      tibial SOS SDS were significantly negatively correlated with body mass index
      (BMI) SDS (r = -0.230, p < 0.001). Finally, subjects that spend more than 3h of
      daily "screen time" (television and personal computer) showed significantly
      decreased SOS values measured both at radius and at tibia. On the contrary, no
      correlation was observed between SOS values and the amount of physical activity
      reported.

PMID- 19577939
TI  - Quantitative computed tomography reveals the effects of race and sex on bone size
      and trabecular and cortical bone density.
AB  - To examine the effects of race and sex on bone density and geometry at specific
      sites within the proximal femur and lumbar spine, we used quantitative computed
      tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men,
      30 CA women, and 17 AA women aged 35-45 yr. Volumetric integral bone mineral
      density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in
      the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric
      cortical BMD (cBMD) was also measured in the femur regions of interest.
      Differences were ascertained using a multivariate regression model. Overall, AA
      subjects had denser bones than CA subjects, but there were no racial differences
      in bone size. Men had larger femoral necks but not larger vertebrae than women.
      The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women
      had higher femoral tBMD but not higher femoral cBMD than CA women. These data
      support the idea that higher hip fracture rates in women compared with men are
      associated with smaller bone size. Lower fracture rates in AA elderly compared
      with CA elderly are consistent with higher peak bone density, particularly in the
      trabecular compartment, and potentially lower rates of age-related bone loss
      rather than larger bone size.

PMID- 19577941
TI  - [Evolution of surgical operations for female for stress urinary incontinence in
      gynaecology departments of Parisian public hospitals between 2002 and 2006].
AB  - OBJECTIVE: To appreciate the evolution of the current surgical practice for
      female for stress urinary incontinence (SUI) in the gynaecologic surgery
      departments of Parisian public hospitals in three different periods of 12 months
      (2002-2003, 2003-2004, and 2006). PATIENTS AND METHODS: The 16 departments were
      surveyed by postal questionnaire about their surgical practice for the treatment
      of female SUI. The number, the type of operation, the type of suburethral tapes
      and their surgical routes were detailed. RESULTS: The participation rate in the
      survey was 87.5% (14/16) for the first two studied periods and 75% (12/16) for
      the last one. The number of SUI procedure decreases between the three periods
      (586, 505, and 263 procedures, respectively; p<0.001). Suburethral slings
      represent the technique of choice for SUI (86.2% in 2002-2003; 92.7% in 2003
      2004, and 98.1% in 2006). Other practices are exceptional. The transobturator
      approach has widely progressed and became the preferred one in 2006 (31.1%;
      64.5%; 95.4% in 2006; p<0.001). No transobturator route was privileged. TVT
      procedures have decreased between the three studied periods (48.3%, 36.5%, and
      4.6% in 2006; p<0.001). TVT-O is the preferred sling in 2006 (120/258, 46.5% of
      suburethral tapes). DISCUSSION AND CONCLUSION: Suburethral tape placement is
      nowadays the main surgical treatment for female SUI amongst members in
      gynaecology departments in Parisian public hospitals. The transobturator approach
      is preferred.

PMID- 19577940
TI  - Polygenic association with total homocysteine in the post-folic acid
      fortification era: the CARDIA study.
AB  - Elevated plasma concentration of total homocysteine (tHcy) has been linked with
      many diseases. tHcy is associated with a variety of factors, including
      polymorphisms in genes involved in homocysteine metabolism. It is not clear
      whether US-mandated fortification of grain products with folic acid has affected
      the association of genetic variants with tHcy levels. We determined tHcy
      concentrations in sera from 997 Caucasians and 692 African Americans participants
      in the Coronary Artery Risk Development in Young Adults (CARDIA) study before and
      after folic acid fortification. DNA was genotyped for variants present in four
      genes involved in homocysteine metabolism: cystathionine beta-synthase (CBS)
      844ins68, methionine synthase (MS) 2756A>G; methionine synthase reductase (MTRR)
      66A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C. A
      greater number of African Americans were homozygous for the MS 2756GG, MTRR 66GG
      and CBS 844ins68 genotypes compared to Caucasians, while prevalence of MTHFR
      677TT and 1298CC genotypes was substantially lower in African Americans compared
      to Caucasians. The overall variance in tHcy levels at y 0, 7 and 15 that can be
      explained by the combined presence of all five variants increased slightly over
      time in Caucasians (17%, y 0; 21%, y 7; and 26%, y 15) and in African Americans
      (13%, y 0; 17% y 7; and 18% y 15) largely due to decrease in tHcy variance.

PMID- 19577942
TI  - [How I perform... the closure of laparoscopic port sites with the Reverdin
      needle].

PMID- 19577943
TI  - [Human embryonic stem cells: from the human embryo transgressed to the
      regenerative medicine of tomorrow].
AB  - Human embryonic stem cells (hESC) are derived from the inner cell mass (ICM) of
      the human blastocyst at day 5 or 6 of the early embryo development. These cells
      display two cardinal features: they are able to differentiate into cell types
      from many if not all human tissue (pluripotency) and they proliferate strongly
      and indefinitely without senescence in vitro. Therefore, hESC are a source of
      choice for stem cells for regenerative medicine and are a reference model to
      study the biology of pluripotency. Since 2004, the French law (loi de Bioethique)
      authorizes hESC research under certain conditions.

PMID- 19577944
TI  - [Should cervical cancer screening undergo some changes?].

PMID- 19577946
TI  - Preparation of ZnO particle with novel nut-like morphology by ultrasonic
      pretreatment and its luminescence property.
AB  - Novel nut-like zinc oxide crystal has been prepared by a low temperature
      hydrothermal method with the presence of Cu(2+) ion. It seemed that the
      ultrasonic pretreatment was the key factor during the preparation process. SEM
      observations revealed that the as-prepared ZnO crystal exhibited nut shape
      showing well-defined crystallographic facets. The cross-section of the ZnO
      crystal was hexagonal of about 800 nm-1 microm in diameter, and the aspect ratio
      was a little smaller than 1:1. The room temperature photoluminescence behavior of
      the nut-like zinc oxide crystal was much stronger than the reference samples.

PMID- 19577945
TI  - [Laparoscopy during pregnancy: experience of the French university hospital of
      Clermont-Ferrand].
AB  - OBJECTIVE: To describe perioperative management and perinatal outcome for
      patients undergoing laparoscopy during pregnancy. PATIENTS AND METHODS: We
      conducted a retrospective study of all cases of laparoscopy during pregnancy
      performed in our university hospital over a period of six years (from February
      2000 to February 2006). RESULTS: We observed 34 cases managed from five to 30
      weeks of gestation (11 cases of adnexal torsion, ten adnexal masses, eight
      appendicitis, one cholecystitis, one sigmoid volvulus, one pelvic peritonitis,
      two heterotopic pregnancies). Open laparoscopy was used in 12 cases. Conversion
      was required in two cases mainly due to adherences (one borderline lesion at 16
      weeks and one tubal cyst torsion at 24 weeks). No maternal complication was
      observed. One miscarriage occurred at Day 1 (peritonitis, five weeks of
      gestation) and one patient opted for abortion. No threatened preterm labour
      occurred after the perioperative course and no neonate required admission in
      neonatology unit. DISCUSSION AND CONCLUSION: This study illustrates safety and
      efficacy of laparoscopy in management of surgical diseases in the gravid patient.
      Emergent indications are the most common, highlighting the need for all
      physicians to know specific recommendations related to laparoscopy during
      pregnancy.

PMID- 19577947
TI  - Collective efficacy in Denver, Colorado: Strengthening neighborhoods and health
      through community gardens.
AB  - Community gardens are viewed as a potentially useful environmental change
      strategy to promote active and healthy lifestyles but the scientific evidence
      base for gardens is limited. As a step towards understanding whether gardens are
      a viable health promotion strategy for local communities, we set out to examine
      the social processes that might explain the connection between gardens, garden
      participation and health. We analyzed data from semi-structured interviews with
      community gardeners in Denver. The analysis examined social processes described
      by community gardeners and how those social processes were cultivated by or
      supportive of activities in community gardens. After presenting results
      describing these social processes and the activities supporting them, we discuss
      the potential for the place-based social processes found in community gardens to
      support collective efficacy, a powerful mechanism for enhancing the role of
      gardens in promoting health.

PMID- 19577949
TI  - Signal transduction regulates schistosome reproductive biology.
AB  - Schistosome parasites exhibit separate sexes and with the evolution of sex they
      have developed an intricate relationship between the male and female worms such
      that signals between the male and female that are initiated at the time of
      mating, regulate female reproductive development and subsequent egg production.
      As the egg stage is responsible for pathogenesis and transmission, understanding
      the molecular mechanisms of female reproductive development may identify novel
      targets for the control of transmission and morbidity of this major world public
      health problem. Recent data have demonstrated that the pairing process,
      proliferation, and differentiation of vitelline cells, expression of female
      specific genes and egg embryogenesis are regulated by the TGFbeta pathway and
      protein tyrosine kinases.

PMID- 19577950
TI  - Mechanisms controlling glideosome function in apicomplexans.
AB  - The glideosome is a unique attribute of the Apicomplexa phylum. This myosin-based
      machine powers parasite motility, migration across biological barriers, host cell
      invasion and egress from infected cells. The timing, duration and orientation of
      gliding motility are tightly regulated to assure establishment of infection.
      Control of glideosome function occurs at several levels. The assembly of the
      molecular motor complex is governed by posttranslational modifications resulting
      from a calcium-dependent signalling cascade. The spatially controlled
      polymerization of actin filaments crucially impacts motility. The relocation of
      glycolytic enzymes in close proximity of the glideosome may enhance the local
      production of energy to sustain movement.

PMID- 19577951
TI  - Molecular and cellular approaches to understanding pathogen-host interactions in
      neglected diseases.

PMID- 19577952
TI  - Synthesis and optical behaviors of 2-(9-phenanthrenyl)-, 2-(9-anthryl)-, and 2-(1
      pyrenyl)-1-alkylimidazole homologues.
AB  - Eight 2-(9-phenanthrenyl)-, 2-(9-anthryl)- and 2-(1-pyrenyl)-1-alkyl
      benzimidazole compounds, three 2-(9-anthryl)-1-alkylphenanthroimidazole compounds
      and five 4,5-diphenyl-1-alkyl-2-(9-anthryl)imidazole compounds were synthesized
      by alkylation reactions of the corresponding benzimidazole, phenanthroimidazole
      or imidazole compounds. 2-(10-Bromo-9-anthryl)-1-alkyl-benzimidazole compounds
      were prepared by bromination reaction of 2-(9-anthryl)-1-alkylbenzimidazole
      compounds. All the synthesized compounds were characterized by elemental
      analysis, (1)H NMR, (13)C NMR, MS or HRMS; their absorption coefficients
      (epsilon), maximum absorption lambda(amax), fluorescence emission maximum
      lambda(em), Stokes shifts and fluorescence quantum yields (Phi(F)) in ethyl
      acetate were determined; their fluorescent lifetimes (T(1) and T(2)) were
      measured in ethyl acetate and in solid state, respectively. The crystal structure
      of 2-(9-anthryl)-1-n-butyl-4,5-diphenylimidazole (12a) was determined to be
      triclinic, space group P-1 types, using single crystal X-ray crystallography
      technique. The results showed that these compounds exhibited moderate
      fluorescence-emission abilities and higher solubility in most organic solvents
      than their corresponding starting materials. The relationships between the
      optical behaviors and structures for these compounds were discussed.

PMID- 19577953
TI  - EPR and optical absorption studies of Cr3+ ions in d-gluconic acid monohydrate.
AB  - EPR studies are carried out on Cr(3+) ions doped in d-gluconic acid monohydrate
      (C(6)H(12)O(7)*H(2)O) single crystals at 77 K. From the observed EPR spectra, the
      spin Hamiltonian parameters g, |D| and |E| are measured to be 1.9919, 349 (x 10(
      4)) cm(-1) and 113 (x 10(-4)) cm(-1), respectively. The optical absorption of the
      crystal is also studied at room temperature. From the observed band positions,
      the cubic crystal field splitting parameter Dq (2052 cm(-1)) and the Racah
      interelectronic repulsion parameter B (653 cm(-1)) are evaluated. From the
      correlation of EPR and optical data the nature of bonding of Cr(3+) ion with its
      ligands is discussed.

PMID- 19577954
TI  - Conformational conversion of DNA G-quadruplex induced by a cationic porphyrin.
AB  - The interactions between cationic meso-tetrakis(4-(N-methylpyridiumyl))porphyrin
      (TMPyP4) and the G-quadruplex (G4) of human telomeric single-strand
      oligonucleotide d(TTAGGG)(2) (S12) have been investigated by means of circular
      dichroism (CD), UV-visible absorption and fluorescence spectroscopies. It is
      found that TMPyP4 can preferentially induce the conformational conversion of the
      G4 structure from the parallel type to the parallel/antiparallel mixture in the
      presence of K(+), and that it can directly induce the formation of antiparallel
      G4 structure from the single-strand oligonucleotide S12 in the absence of K(+).
      Furthermore, the comparable experiments of TMPyP4 with two single-strand
      oligonucleotides S6 d(TTAGGG) and S24 d(TAGGG(TTAGGG)(3)T) in the absence of K(+)
      show that TMPyP4 can also induce the formation of antiparallel G4 from S24 but
      not from S6, indicating that the end-loops of the G4 structure are the key
      factors for the formation of G4 induced by TMPyP4.

PMID- 19577955
TI  - Synthesis and characterization of thiosalicylic acid stabilized gold
      nanoparticles.
AB  - We report the synthesis of photoluminescent Au nanoparticles of varying sizes
      stabilized with a carboxylate group terminated aromatic thiol, thiosalicylic
      acid. The formation of Au nanoparticles and its stabilization with the thiol has
      been characterized by different spectroscopic and thermal methods. The water
      solubility, along with the low degree of aggregation and photoluminescence,
      enhances their suitability for biological applications. The photoluminescence may
      be due to charge transfer of the Au core with the stabilizing ligand.

PMID- 19577956
TI  - Factors affecting health care workers' adoption of a website with infection
      control guidelines.
AB  - GOAL: To identify factors that could affect health care workers' (HCWs) adoption
      of a website for communicating infection control guidelines. METHODS: In total,
      20 semi-structured interviews were conducted with HCWs in 5 different
      occupational groups and 4 different hospitals in the Netherlands and Germany. A
      website communicating guidelines for the prevention and control of Methicillin
      Resistant Staphylococcus aureus served as a casus. The HCWs, the majority of whom
      had prior experience with the website, were asked to give their opinions about
      factors that hinder or facilitate adoption of the website in practice. The
      interviews were based on the PRECEDE (Predisposing, Reinforcing, and Enabling
      Causes in Educational Diagnosis and Evaluation) model complemented by quality
      criteria for health-related websites. This model encompasses different categories
      of factors relevant to technology adoption in health care. RESULTS: A total of
      361 interview statements were relevant to the four main categories of the PRECEDE
      model, yielding the following observations: (1) Technological factors (72
      statements): The usability, design, and relevance of the website were positively
      valued. The website enabled HCWs to access contextually relevant information
      quickly. The website's credibility was evaluated rather negatively, as
      respondents perceived that the website's guidelines were not in concurrence with
      the best available evidence and it was not clear to HCWs who created the website.
      (2) Individual factors (85 statements): Respondents, particular infection control
      professionals, showed individual resistance to the website because they preferred
      to use their personal knowledge and experience (and communication with
      colleagues) over online sources. (3) Work-related factors (53 statements):
      Respondents perceived high work pressure during working hours as an impediment to
      consulting the website. In contrast, respondents thought the website might lower
      work pressure for infection control professionals, as they will receive fewer
      questions from HCWs. (4) Organizational factors (131 statements): Interpersonal
      (face-to-face) communication between HCWs from different occupational groups in
      both a formal (training) and informal (feedback) manner was seen as the most
      stimulating factor behind website use. The respondents identified infection
      control nurses as the most important opinion leaders. CONCLUSION: Factors from
      multiple categories determine HCWs' adoption of web-based guidelines, but the
      organization appeared to be a paramount reinforcer of initiation and maintenance
      of technology adoption among HCWs. In order eliminate resistance and create
      ownership among HCWs toward the website, leading to a willingness to integrate
      the website into routine care, it is essential to more actively involve HCWs in
      the early phases of the design process.

PMID- 19577958
TI  - Night and day morphologies in a planktonic dinoflagellate.
AB  - We describe remarkable diurnal changes in the morphology of the planktonic
      dinoflagellate Ceratium ranipes. The species is distinguished by the unusual
      appendages, known as toes or fingers, protruding from its horns. Varieties have
      been described based on the characteristics of the fingers. We discovered that
      cultures, maintained on a 12:12 photoperiod, when examined during the dark period
      were composed of 'finger-less' cells. Monitoring of isolated cells revealed a
      diurnal cycle of distinct changes in morphology with daytime cells showing
      appendages, well-stocked with chlorophyll, and the absence of the fingers at the
      end of the photoperiod. Fingers are absorbed at the end of the light period and
      re-grown at the end of the dark period. Sampling the Bay of Villefranche, we
      found the distinct morphologies in a natural population at night and during the
      day.

PMID- 19577957
TI  - Molecular typing of clinical adenovirus specimens by an algorithm which permits
      detection of adenovirus coinfections and intermediate adenovirus strains.
AB  - BACKGROUND: Epidemiological data suggest that clinical outcomes of human
      adenovirus (HAdV) infection may be influenced by virus serotype, coinfection with
      multiple strains, or infection with novel intermediate strains. In this report,
      we propose a clinical algorithm for detecting HAdV coinfection and intermediate
      strains. STUDY DESIGN: We PCR amplified and sequenced subregions of the hexon and
      fiber genes of 342 HAdV-positive clinical specimens obtained from 14 surveillance
      laboratories. Sequences were then compared with those from 52 HAdV prototypic
      strains. HAdV-positive specimens that showed nucleotide sequence identity with a
      corresponding prototype strain were designated as being of that strain. When
      hexon and fiber gene sequences disagreed, or sequence identity was low, the
      specimens were further characterized by viral culture, plaque purification,
      repeat PCR with sequencing, and genome restriction enzyme digest analysis.
      RESULTS: Of the 342 HAdV-positive clinical specimens, 328 (95.9%) were single
      HAdV strain infections, 12 (3.5%) were coinfections, and 2 (0.6%) had
      intermediate strains. Coinfected specimens and intermediate HAdV strains
      considered together were more likely to be associated with severe illness
      compared to other HAdV-positive specimens (OR=3.8; 95% CI=1.2-11.9). CONCLUSIONS:
      The majority of severe cases of HAdV illness cases occurred among
      immunocompromised patients. The analytic algorithm we describe here can be used
      to screen clinical specimens for evidence of HAdV coinfection and novel
      intermediate HAdV strains. This algorithm may be especially useful in
      investigating HAdV outbreaks and clusters of unusually severe HAdV disease.

PMID- 19577959
TI  - Physiological attributes of triathletes.
AB  - Triathlons of all distances can be considered endurance events and consist of the
      individual disciplines of swimming, cycling and running which are generally
      completed in this sequential order. While it is expected that elite triathletes
      would possess high values for submaximal and maximal measures of aerobic fitness,
      little is known about how these values compare with those of single-sport
      endurance athletes. Earlier reviews, conducted in the 1980s, concluded that
      triathletes possessed lower V(O2(max)) values than other endurance athletes. An
      update of comparisons is of interest to determine if the physiological capacities
      of elite triathletes now reflect those of single-sport athletes or whether these
      physiological capacities are compromised by the requirement to cross-train for
      three different disciplines. It was found that although differences in the
      physiological attributes during swimming, cycling and running are evident among
      triathletes, those who compete at an international level possess V(O2(max))
      values that are indicative of success in endurance-based individual sports.
      Furthermore, various physiological parameters at submaximal workloads have been
      used to describe the capacities of these athletes. Only a few studies have
      reported the lactate threshold among triathletes with the majority of studies
      reporting the ventilatory threshold. Although observed differences among
      triathletes for both these submaximal measures are complicated by the various
      methods used to determine them, the reported values for triathletes are similar
      to those for trained cyclists and runners. Thus, from the limited data available,
      it appears that triathletes are able to obtain similar physiological values as
      single-sport athletes despite dividing their training time among three
      disciplines.

PMID- 19577960
TI  - Policy and practice in teenage and young adult cancer care in England: looking to
      the future.
AB  - This paper outlines the current policy and service developments for the provision
      of cancer care for teenagers, young adults and their families in England. Key
      implications in terms of the settings and place of care, the centrality of the
      multidisciplinary team, the improvement of outcomes in TYA cancer care together
      with psychosocial issues are examined in more depth alongside the existing
      evidence base. In terms of the development of high quality, accessible specialist
      TYA cancer care and the development of a rigorous evidence base for the practice
      of TYA cancer care the next few years are crucial. The way forward is complex and
      challenging but the framework is in place in England to comprehensively improve
      the care and outcomes of teenagers and young adults with cancer.

PMID- 19577961
TI  - Biomarkers of premature atherosclerosis.
AB  - C-reactive protein (CRP) is an acute phase protein and a biochemical marker with
      important prognostic value for cardiovascular events. Interleukins IL-1 and IL-6
      are implicated in the pathogenesis of atherosclerosis and are associated with
      CRP. Apolipoproteins ApoA-I and ApoB are the main lipid metabolic markers
      implicated in the development and progression of atherosclerosis. Fibrinogen has
      also been proposed to be a major independent risk factor for cardiovascular
      events. Because premature atherosclerosis precedes the development of
      cardiovascular disease, identification of the associated biomarkers is of great
      importance. However, further studies will be needed to determine whether or not
      these markers are useful predictors of future cardiovascular events. Here, we
      review the roles of specific biomarkers that have been implicated in premature
      atherosclerosis.

PMID- 19577963
TI  - The BASICS of treating symptomatic basilar artery thrombosis.

PMID- 19577964
TI  - A novel technique for demonstrating the real-time subsurface tissue thermal
      profile of two energized surgical instruments.
AB  - Currently the primary methods for obtaining hemostasis during minimally invasive
      surgery include systems that incorporate either ultrasonic or radiofrequency
      energy. Although the use of improved energy systems has dramatically facilitated
      laparoscopic dissection and hemostasis, the threat of thermal collateral damage
      remains and detracts from the usefulness of these devices. Traditionally the
      thermal spread from these instruments has been determined with a combination of
      in situ dynamic thermography and histopathologic studies that result in varying
      degrees of cross-correlation. The ability to obtain a real-time subsurface tissue
      thermal profile without the use of thermography in either an electrosurgical or
      ultrasonic device is feasible with a microthermistor placed at a predetermined
      distance and depth from the instrument tool edge. A comparison with traditional
      thermographic measurements and their correlation with histologic study are
      warranted with future studies.

PMID- 19577965
TI  - A risk-based analysis of the AAPS conference report on quantitative bioanalytical
      methods validation and implementation.
AB  - The 3rd American Association of Pharmaceutical Scientists (AAPS)/Food and Drug
      Administration (FDA) Bioanalytical workshop in 2006 concluded with several new
      recommendations regarding the validation of bioanalytical methods in a report
      published in 2007. It was aimed to conciliate or adapt validation principles for
      small and large molecules and an opportunity to revisit some of the major
      decision rules related to acceptance criteria given the experience accumulated
      since 1990. The purpose here is to provide a "risk-based" reading of the
      recommendations of 3rd AAPS/FDA Bioanalytical Workshop. Five decision rules were
      compared using simulations: the proposed pre-study FDA and Total Error Rules, the
      rules based on the beta-Expectation Tolerance and beta-gamma-Content Tolerance
      Interval and, finally, the 4-6-20 rule for in-study acceptance of runs. The
      simulation results demonstrated that the beta-Expectation Tolerance Rule controls
      appropriately the risk. The beta-gamma-Content Tolerance Interval was found to be
      too conservative, depending on the objective, and to lead to a high rate of
      rejection of procedures that could be considered as acceptable. On the other
      side, the FDA and the AAPS/FDA workshop Total Error Rule, combined or not, did
      not achieve their intended objective. With these rules, the risk is high to
      deliver results in study that would not meet the targeted acceptance criteria.
      This can be explained because, first, there is confusion between the quality of a
      procedure and the fitness of purpose of the results it could produce and, second,
      between the initial performances of a procedure, for example evaluated during pre
      study validation and the quality of the future results.

PMID- 19577962
TI  - Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery
      International Cooperation Study (BASICS): a prospective registry study.
AB  - BACKGROUND: Treatment strategies for acute basilar artery occlusion (BAO) are
      based on case series and data that have been extrapolated from stroke
      intervention trials in other cerebrovascular territories, and information on the
      efficacy of different treatments in unselected patients with BAO is scarce. We
      therefore assessed outcomes and differences in treatment response after BAO.
      METHODS: The Basilar Artery International Cooperation Study (BASICS) is a
      prospective, observational registry of consecutive patients who presented with an
      acute symptomatic and radiologically confirmed BAO between November 1, 2002, and
      October 1, 2007. Stroke severity at time of treatment was dichotomised as severe
      (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was
      less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a
      modified Rankin scale score of 4 or 5, or death. Patients were divided into three
      groups according to the treatment they received: antithrombotic treatment only
      (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary
      intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis;
      or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical
      thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR)
      for treatment effects were adjusted for age, the severity of neurological
      deficits at the time of treatment, time to treatment, prodromal minor stroke,
      location of the occlusion, and diabetes. FINDINGS: 619 patients were entered in
      the registry. 27 patients were excluded from the analyses because they did not
      receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were
      analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall,
      402 (68%) of the analysed patients had a poor outcome. No statistically
      significant superiority was found for any treatment strategy. Compared with
      outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the
      same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after
      IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with
      IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe
      deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88,
      0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar
      after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION:
      Most patients in the BASICS registry received IAT. Our results do not support
      unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in
      patients with an acute BAO needs to be assessed in a randomised controlled trial.
      FUNDING: Department of Neurology, University Medical Center Utrecht.

PMID- 19577967
TI  - Impact on outcome of the route of conduit transposition after transhiatal
      oesophagectomy: A randomized controlled trial.
AB  - AIM: To assess the influence of the route of conduit transposition after
      transhiatal oesophagectomy on the postoperative morbidity and mortality and late
      outcome at 6 months. METHODS: Patients with oesophageal carcinoma, undergoing
      transhiatal oesophagectomy (gastric conduit), were randomized to either anterior
      or posterior route of conduit transposition. Patients with advanced tumour,
      distant metastasis, extensive invasion of the stomach, previous gastric surgery,
      any anterior mediastinal abnormality detected on preoperative imaging, ASA grade
      III/IV and poor preoperative pulmonary function were excluded. Intraoperative
      complications, postoperative morbidity and mortality and late outcomes were
      compared. RESULTS: Of the 49 patients (34 men), 24 patients were randomized to
      the anterior mediastinal route and 25 to the posterior. The mean duration of the
      operative procedure (anterior: 235min; posterior: 225min) and the mean blood loss
      (anterior: 531ml; posterior: 538ml) were not statistically different. The most
      common complications were pulmonary and cardiac and comparable in both groups.
      Four patients died postoperatively. At 6-month follow-up the incidence of
      dysphagia, anastomotic stricture, anastomotic recurrence, aspiration and reflux
      symptoms and weight gain were similar. CONCLUSIONS: The route of conduit
      transposition did not affect the outcome. However, an individualized approach
      depending upon the operative findings, radicality of the procedure, and perceived
      need for postoperative adjuvant therapy may be useful.

PMID- 19577968
TI  - Pitta Vac: a quick and easy technique for upper and lower limb vacuum therapy.

PMID- 19577969
TI  - Repositioning of the malpositioned ear with a new technique of fascia lata
      suspension.

PMID- 19577970
TI  - Herpes zoster in the median nerve distribution.

PMID- 19577966
TI  - Endocytic proteins in the regulation of nuclear signaling, transcription and
      tumorigenesis.
AB  - Accumulating evidence argues that many proteins governing membrane sorting during
      endocytosis participate also in nuclear signaling and transcriptional regulation,
      mostly by modulating the activity of various nuclear factors. Some adaptors and
      accessory proteins acting in clathrin-mediated internalization, as well as
      endosomal sorting proteins can undergo nuclear translocation and affect gene
      expression directly, while for others the effects may be more indirect. Although
      it is often unclear to what extent the endocytic and nuclear functions are
      interrelated, several of such proteins are implicated in the regulation of cell
      proliferation and tumorigenesis, arguing that their dual-function nature may be
      of physiological importance.

PMID- 19577971
TI  - A practical approach to managing flipped tissue expander valves.

PMID- 19577972
TI  - Aplasia cutis congenita. A case of scalp defect repair using two opposing
      bipedicled local flaps.
AB  - Aplasia cutis congenita is a rare congenital condition characterised by the
      absence of some or all layers of the skin. It may also be associated with absence
      of underlying muscle and bone. Where dura is exposed there exists a risk of
      ulceration and haemorrhage and thus primary closure is indicated. We report a
      case of cutis aplasia successfully closed with opposing bipedicled flaps. To our
      knowledge this is a novel approach which offers a simple safe technique that can
      be applied in the neonate.

PMID- 19577973
TI  - Magnetic resonance angiography to evaluate septocutaneous perforators in free
      fibula flap transfer.
AB  - BACKGROUND: In harvesting free fibula composite flaps, preoperative knowledge of
      the lower limb vascular anatomy is essential to prevent ischaemic complications
      or flap failure. Magnetic resonance angiography (MRA) allows imaging of the
      septocutaneous perforators (< or = 1-2mm diameter) of the peroneal artery used in
      the free fibula flap. METHODS: We investigated seven patients undergoing the free
      fibula flap preoperatively with high-resolution MRA images to study the
      following: 1) tibio-peroneal anatomy, 2) peripheral artery disease, 3) the
      positions of the perforator vessels on the peroneal artery and their course in
      the posterolateral intermuscular septum and 4) the cutaneous distribution of the
      perforators, and to compare them to surgical findings. RESULTS: MRA demonstrated
      tibio-peroneal anatomy in sufficient detail to exclude anatomic variants and
      significant peripheral vascular disease, detected septocutaneous perforators
      arising from the peroneal artery coursing in the posterolateral intermuscular
      septum and determined the skin terminus of the septocutaneous perforators. All
      septocutaneous perforators found during surgery were detected prospectively on
      high-resolution MRA. CONCLUSION: Lower leg vascular anatomy assessment with high
      resolution MRA determined the location of the septocutaneous perforators of the
      peroneal artery preoperatively with accuracy and precision. This anatomical
      knowledge provides for a safer procedure and the opportunity to plan surgical
      details preoperatively.

PMID- 19577974
TI  - [Ophthalmic manifestations in Wegener's granulomatosis. Review of literature
      about an observation].
AB  - Wegener's granulomatosis mainly affects the upper respiratory tract, the lungs
      and the kidneys but many other organs and tissues may be affected, as well
      including any eye structures. Ocular and orbital structures involvement is
      frequently encountered, sometimes inaugural, with or without obvious systemic
      manifestations, sometimes leading to visual loss. The most frequent ophthalmic
      lesions are inflammatory orbital disease, (necrotising) scleritis with or without
      keratopathy, episcleritis, conjunctivitis and even conjunctival ulcer,
      nasolacrimal ducts obstruction, uveitis, retinal vasculitis and even central
      retinal vascular occlusion, optic neuritis. These ocular lesions result either
      from extensive granulomatous inflammation or from focal vasculitis. These
      complications need to be recognized as soon as possible so that an early
      diagnosis may allow the appropriate treatment meant to keep both visual and even
      general prognosis.

PMID- 19577977
TI  - On the current epidemic outburst of meta-analytic rage in interventional
      cardiology.

PMID- 19577978
TI  - Transcatheter aortic valve implantation (TAVI): how to interpret the data and
      what data is required?

PMID- 19577979
TI  - Clinical endpoints in transcatheter aortic valve implantation: a call to ARC for
      standardised definitions.

PMID- 19577980
TI  - Counting the score: the SYNTAX Score and coronary risk.

PMID- 19577981
TI  - Sustain Health development in Africa through Responsible Education (SHARE).

PMID- 19577982
TI  - Percutaneous coronary intervention for bifurcation lesions: 2008 consensus
      document from the fourth meeting of the European Bifurcation Club.

PMID- 19577983
TI  - Assessment of the SYNTAX score in the Syntax study.
AB  - AIMS: The SYNTAX score has been designed to better anticipate the risks of
      percutaneous or surgical revascularisation, taking into account the functional
      impact of the coronary circulation with all its anatomic components including the
      presence of bifurcations, total occlusions, thrombus, calcification, and small
      vessels. The purpose of this paper is to describe the baseline assessment of the
      SYNTAX score in the Syntax randomised trial, the corelab reproducibility, the
      potential difference in score assessment between the investigator and the
      corelab, and to ascertain the impact on one-year outcome after either
      percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG)
      in patients with complex coronary artery disease. METHODS AND RESULTS: To assess
      the reliability of Syntax scoring, 100 diagnostic angiograms from the Syntax
      trial were randomly selected and assessed independently by two observers. Intra
      observer variability was assessed by analysing 91 sets of angiograms after an
      interval of at least eight weeks by one of the observers. Clinical outcomes in
      the randomised cohort of the Syntax trial up to one year are presented with
      stratification by tertile group of the SYNTAX score. The weighted kappa value for
      the inter-observer reproducibility on the global score was 0.45, while the intra
      observer weighted kappa value was 0.59. The SYNTAX score as calculated by
      investigators consistently underscored the corelab score by 3.4 points. When the
      Syntax randomised cohort was stratified by tertiles of the SYNTAX score, there
      were similar or non-significantly different MACCE rates in those with low or
      intermediate scores; however in the top tertile the MACCE rate was greater in
      those receiving PCI compared to CABG. CONCLUSIONS: The SYNTAX score is a visual
      coronary score with an acceptable corelab reproducibility that has an impact on
      the one-year outcome of those having PCI, whereas it has no effect on the one
      year outcome following surgical revascularisation. The SYNTAX score tool is
      likely to be useful in a wide range of patients with complex coronary disease.

PMID- 19577984
TI  - Patient selection to enhance the long-term benefit of first generation drug
      eluting stents for coronary revascularisation procedures. Insights from a large
      multicentre registry.
AB  - AIMS: To evaluate the long-term clinical outcome after drug-eluting stents (DES)
      implantation, and to test if patient selection could enhance their net clinical
      benefit. METHODS AND RESULTS: We assessed the incidence of major adverse cardiac
      events (MACE=death, acute myocardial infarction, and target vessel
      revascularisation, TVR) and angiographic stent thrombosis (ST) during 3-year
      follow-up in a prospective multicentre registry. Propensity-score analysis to
      adjust for different clinical, angiographic and procedural characteristics was
      performed. Overall, 14,115 patients enrolled in the registry received solely BMS
      (n=9,565) or DES (n=4,550). The incidence of definite ST was 0.6% for BMS and
      1.3% for DES (p=0.003). The propensity-score adjusted incidence of cardiac death
      and myocardial infarction was similar between the two groups (DES 11.9% vs. BMS
      12.1%, HR 0.90, 95% CI 0.77-1.04), whereas DES were associated with lower rates
      of TVR (DES 11.6% vs. BMS 15.2%, HR 0.67, 95% CI 0.59-0.76). The efficacy of DES
      in reducing TVR increased with increasing likelihood of TVR at baseline.
      CONCLUSIONS: The beneficial effect of DES in reducing new revascularisations
      compared to BMS extends out to three years without a significantly worse overall
      safety profile. The benefit seems more evident in patients with the highest
      baseline risk of clinical restenosis.

PMID- 19577986
TI  - Anatomo-pathological analysis after CoreValve Revalving system implantation.
AB  - AIMS: Significant technological improvements have made percutaneous aortic valve
      replacement (PAVR) simpler and safer, but the behaviour of the implanted valve
      over time remains unknown. We report the anatomo-pathological analysis of
      patients who died at different time intervals post PAVR with the CoreValve
      Revalving System. METHODS AND RESULTS: In our early experience, 21 patients
      underwent CoreValve implantation between 12/2005 and 02/2007. Among the 11 deaths
      at one year follow-up, four patients had an autopsy with macro and microscopic
      analysis. The device was divided in three parts during pathological assessment:
      the lower portion (area 1), the leaflets (area 2) and the upper part (area 3).
      The CoreValves were implanted for 3, 13, 104 and 350 days. Gross examination
      showed neointimal tissue covering most of the frame struts in contact with the
      aortic wall, but areas of high velocity blood flow were bare. Histopathology
      examination demonstrated fibrin deposition and inflammatory response early after
      valve implantation, followed by neointimal coverage with progressive regression
      of the inflammatory response over time. CONCLUSIONS: While waiting for results of
      longer term PAVR echocardiographic follow-up, the anatomic assessment is
      encouraging with neointimal coverage of the native valve site and no excessive
      pannus formation occurring over the valve leaflets.

PMID- 19577987
TI  - Percutaneous suture edge-to-edge repair of the mitral valve.
AB  - AIMS: To describe a new approach to percutaneous mitral valve repair and an
      illustrative first-in-man experience, we introduce a suture mediated "double
      orifice", "edge-to-edge" procedure which can be an effective surgical therapy for
      mitral regurgitation (MR) in selected patient. METHODS AND RESULTS: We describe a
      novel percutaneous approach to double orifice mitral repair utilising an intra
      cardiac suture based system. The procedure was performed in 15 patients in four
      international centres. Endovascular suture based double orifice mitral repair was
      feasible with an acute reduction in the severity of MR by > or = 1 grade in nine
      of 15 patients. At 30 days improvement in MR appeared durable in six patients.
      Clinical utility was limited by technical difficulties, the inadequacies of
      current imaging modalities and suture dehiscence. CONCLUSIONS: Percutaneous
      endovascular suture based cardiac repair is feasible. However, in utilising the
      current device clinical benefit was limited and the repair not durable. In the
      future, similar endovascular approaches may enable more complex cardiac repair.

PMID- 19577985
TI  - Expanded use of the TAXUS Express Stent: two-year safety insights from the 7,500
      patient ARRIVE Registry programme.
AB  - AIMS: We report 2-year outcomes in a large unselected drug-eluting stent
      population (N=7,492) in the TAXUS Express2 ARRIVE post-market surveillance
      programme (101 U.S. sites). METHODS AND RESULTS: No specific inclusion/exclusion
      criteria were mandated; patients enrolled at procedure initiation. Two-year
      follow-up was 94%, with independent adjudication of major cardiac events,
      monitoring of patients with cardiac events and an additional 10-20% sample by
      site. Most ARRIVE cases (64%, n=4,794) typified expanded use based on
      patient/lesion characteristics outside the simple use (single vessel/stent)
      pivotal trial populations. These expanded use patients had higher 2-year rates
      than simple use patients for mortality (7.8% vs. 4.2%, P<0.001), myocardial
      infarction (MI, 3.9% vs. 2.2%, P<0.001), target lesion revascularisation (TLR,
      9.2% vs. 5.4%, P<0.001), and stent thrombosis (3.3% vs. 1.4%, P<0.001). Among
      subgroups with renal disease, chronic total occlusion (CTO), lesion >28 mm,
      reference vessel diameter (RVD) <2.5 mm, multivessel stenting, acute MI,
      bifurcation, vein graft, or in-stent restenosis, TLR ranged from 3.8% to 8.9% in
      year one, and from 1.3% to 6.0% during year two. CONCLUSIONS: Mortality and stent
      related events were higher in expanded use than simple use patients in the
      pivotal trials. ARRIVE provides a detailed estimate of procedural and 2-year
      outcomes in such real-world patients.

PMID- 19577988
TI  - A multicentre evaluation of the safety of intracoronary optical coherence
      tomography.
AB  - AIMS: Optical coherence tomography (OCT) is increasingly being applied to the
      coronary arteries. However, the risks associated with the imaging procedure are
      not yet well defined. The purpose of the present multicentre registry was to
      assess the acute complications associated with the clinical use of intra-coronary
      OCT in a large number of patients. METHODS AND RESULTS: Consecutive patients from
      six centres who had OCT examination were retrospectively included. All adverse
      events and complications, even if transient, were noted. Risks were categorised
      into: 1) self-limiting 2) major complications including major adverse cardiac
      events (MACE) and 3) mechanical device failure. A total of 468 patients underwent
      OCT examination for evaluation of: plaque (40.0%), percutaneous coronary
      intervention (28.2%) or follow-up stent tissue coverage (31.8%). OCT was
      performed using a non-occlusive flush technique in 45.3% with a mean contrast
      volume of 36.6+/-9.4ml. Transient chest pain and QRS widening/ST
      depression/elevation were observed in 47.6% and 45.5% respectively. Major
      complications included five (1.1%) cases of ventricular fibrillation due to
      balloon occlusion and/or deep guide catheter intubation, 3 (0.6%) cases of air
      embolism and one case of vessel dissection (0.2%). There were no cases of
      coronary spasm or MACE during or within the 24 hour period following OCT
      examination. CONCLUSIONS: OCT is a specialised technique with a relatively steep
      learning curve. Major complications are uncommon and can be minimised with
      careful procedural planning and having an awareness of the potential contributory
      risks, especially deep guide catheter intubation during contrast flushing.
      Upcoming developments will make OCT more practical and less procedurally
      demanding, also potentially conserving contrast volume considerably.

PMID- 19577989
TI  - Ex vivo analysis of human coronary bifurcation anatomy: defining the main vessel
      to-side-branch transition zone.
AB  - AIMS: Defining vessel diameters and angles that comprise coronary side-branch
      intersections could assist in tailoring treatments to match anatomy, improve
      haemodynamic flow, and minimise mechanical trauma. We sought to characterise
      intersections of main vessels and side-branches by measuring actual diameters,
      angles, and shapes at the ostia in human coronary arteries. METHODS AND RESULTS:
      Polymer casts were created using coronary trees from 23 adult cadaver hearts.
      Seventy-five arterial intersections between main vessels and side-branches were
      captured using the combination of a microscope (Smartscope MVP100) and computer
      program (Gage-X metrology software) specifically calibrated for video-based
      inspection and measurement (34-fold magnification). The intersection between main
      vessels and side-branches was a multifaceted, curvilinear transition rather than
      a bisecting angle. The shape of the ostia was typically elliptical rather than
      circular. Mean diameters were 2.88 mm in proximal main vessels, 2.34 mm in ostia,
      and 2.00 mm in side-branches (first-level branches). Obtuse proximal (150
      degrees) and distal (111 degrees) angles with accentuated side-branch taper
      create a "barn door" effect with wider curvature at the bottom. CONCLUSIONS:
      Matching treatments to these various forms of asymmetry at the main vessel-to
      side-branch intersection may minimise injury and optimise scaffolding, and
      haemodynamic flow.

PMID- 19577990
TI  - Long-term clinical and angiographic outcomes of the sleeve technique on non-left
      main coronary bifurcation lesions.
AB  - AIMS: The purpose of this study was to examine the long-term results of the
      sleeve technique, which is a modification of the crush technique and capable of
      increasing the success of final kissing balloon inflation (FKB) in the treatment
      of non-left-main coronary bifurcation lesions. METHODS AND RESULTS: Forty-five
      patients with 45 non-left-main coronary bifurcation stenoses were treated with
      drug-eluting stents (DES) using the sleeve technique and prospectively evaluated.
      Follow-up angiography was performed on 41 patients (91%) at nine months. The mean
      age of patient was 65 years with predominance of male (73%); FKB was successfully
      performed in all patients. Post-procedure myocardial infarction was observed in
      four patients, leading to an in-hospital major adverse cardiac event (MACE) rate
      of 9%. At angiographic follow-up, the late loss in the main vessel and side
      branch was 0.18+/-0.26 mm and 0.29+/-0.27 mm, respectively. Binary angiographic
      restenosis was seen in two patients (4.7%) at main vessel and one patient (2.4%)
      at side-branch. At 1-year follow-up, there were two non-cardiac deaths and three
      patients needed revascularisation. CONCLUSIONS: The use of the sleeve technique
      and DES in the treatment of non-left-main coronary bifurcation lesions is
      associated with a low angiographic restenosis, particularly at side branch
      ostium, and long-term safety.

PMID- 19577991
TI  - PRO-Kinetic: results from an "all-comers" single centre clinical experience.
AB  - AIMS: To conduct a clinical registry of consecutive "real world" patients treated
      using the PRO-Kinetic stent at Rabin Medical Centre between January 2006 and
      March 2008. METHODS AND RESULTS: Our study included 515 consecutive patients
      treated for 540 lesions. We had a 100% follow-up rate at six months. The
      patients' characteristics are noted as having a 43% rate of diabetics and a 17%
      renal insufficiency. Indications for angioplasty included patients with either
      stable or unstable clinical scenarios and 60% of the lesions were of class B2/C.
      The mean RVD was 2.81 mm and lesions length was 12.6 mm prior to PCI and with
      angiographic success in 99.8% of treated lesions. The six month clinical outcome
      data were as follow: MACE rate of 8.7% with 3.5% total mortality, 1.9% cardiac
      mortality, 1.4% of any MI and TVR rate of 6.4% per treated patient and 6.7% per
      treated lesion and 0.4% rate of stent thrombosis. CONCLUSIONS: Based on our
      findings, 1) The PRO-Kinetic clinical data shows excellent results on a large
      group of coronary patients, treated consecutively. 2) The data should emphasise
      the remaining role of 'state of the art' non DES platforms (i.e. such as PRO
      Kinetic) for patients with a wide variety of characteristics and/or clinical
      syndromes.

PMID- 19577992
TI  - Choice of arterial access site and outcomes in patients with acute coronary
      syndromes managed with an early invasive strategy: the ACUITY trial.
AB  - AIMS: The purpose of this study was to evaluate the impact of arterial access
      site on bleeding and ischaemic outcomes, overall and by treatment strategy, in
      patients with acute coronary syndromes (ACS). METHODS AND RESULTS: In the ACUITY
      trial, 13,819 patients with moderate and high-risk ACS were randomised to either
      heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor
      (GPI), bivalirudin plus a GPI, or bivalirudin alone. Per operator choice, femoral
      access was utilised in 11,989 patients (93.8%) and radial access in 798 patients
      (6.2%). There was no significant difference in composite ischaemia between the
      radial and femoral approaches at 30 days (8.1% vs 7.5%, p=0.18) or 1 year (14.7%
      vs 15.5%, p=0.77), although fewer major bleeding complications occurred with the
      use of radial access (3.0%vs4.8%, p=0.03). Use of bivalirudin monotherapy was
      associated with significantly less 30-day major bleeding than heparin plus GPI
      after femoral access (3.0% vs 5.8%, p<0.0001), but not with radial access (4.2%
      vs 2.2%, P=0.19). Major or minor organ bleeding was reduced with bivalirudin
      monotherapy compared to heparin plus GPI to a similar extent with both femoral
      (4.1% vs 7.4%, P<0.0001) and radial (4.9% vs 7.2%, P=0.26) access. CONCLUSIONS:
      Transradial compared to femoral arterial access is associated with similar rates
      of composite ischaemia and with fewer major bleeding complications in patients
      with ACS managed invasively. Bivalirudin monotherapy compared to heparin plus
      GPIs significantly reduces access site related major bleeding complications with
      femoral but not radial artery access, though non-access site related bleeding is
      reduced by bivalirudin monotherapy in all patients.

PMID- 19577993
TI  - Very late changes in the dilated lesion following coronary balloon angioplasty: a
      17 year serial quantitative angiographic study.
AB  - AIMS: Limited data are available on the changes that occur at the dilated site
      many years after coronary balloon angioplasty. The development of bioabsorbable
      stents may increase the importance of understanding the long term changes that
      occur in an unscaffolded coronary artery following balloon-mediated injury.
      METHODS AND RESULTS: This study evaluated, by serial quantitative angiography,
      the natural history of changes that occurred in the dilated segment between early
      (mean seven months), late (mean 4.5 years) and very late (mean 17 years) follow
      up after balloon angioplasty. Of 127 consecutive patients (174 lesions) with
      successful coronary angioplasty, 125 underwent early, 84 late and 47 very late
      angiographic follow-up (75% of eligible survivors). The mean lesion diameter
      stenosis decreased from 36+/-11% at early to 26+/-15% at late follow-up
      (p<0.0001), and then increased again to 35+/-25% by very late follow-up
      (p=0.003). Although stenosis severity at early follow-up angiography predicted
      lesion regression at late follow-up, there was no significant correlation between
      late and very late follow-up lesion severity. CONCLUSIONS: After coronary
      angioplasty, lesion regression at the dilated site from 7 months to 4.5 years is
      followed by slow lesion progression over the next 12 years.

PMID- 19577995
TI  - Characterisation of atherosclerotic plaque by spectral similarity of
      radiofrequency intravascular ultrasound signals.
AB  - AIMS: The aim of this paper is to report a method of atherosclerotic plaque
      tissue characterisation based on pattern recognition and assess its accuracy
      under conditions of potential clinical relevance. METHODS AND RESULTS: Excised
      saline infused human arteries were imaged using IVUS with RF acquisition. 40% of
      the vessels were re-imaged with human blood infusion. A database of approximately
      12000 image regions-of-interest (ROIs) of histologically established types was
      used to design a pattern recognition algorithm to predict the tissue type of a
      given ROI by comparing its RF-spectrum against the database, and also to estimate
      the confidence of prediction. Ex vivo validation demonstrated accuracies at the
      highest level of confidence as: 97%, 98%, 95%, and 98% for necrotic, lipidic,
      fibrotic and calcified regions respectively. Good agreement with histology was
      shown in an in vivo swine animal model. CONCLUSIONS: Ex vivo validation
      demonstrated the ability to characterise plaque tissue using an IVUS+RF system
      and a method incorporating (1) full spectral information (2) spectral similarity
      (3) estimating confidence of characterisation and, (4) ability to characterise
      plaque imaged through blood. Promising results were demonstrated in a live animal
      model. This approach may have potential for accurate and reproducible plaque
      characterisation in vivo.

PMID- 19577994
TI  - Three-dimensional reconstruction allows accurate quantification and length
      measurements of coronary artery stenoses.
AB  - AIMS: The aim of this prospective study was to evaluate the feasibility and
      accuracy of a recently developed 3D system (CardiOp-B; Paieon Medical Ltd.,
      Israel) as compared to a validated quantitative coronary angiography (QCA) system
      (Siemens Quantcor, Siemens Medical Solutions). METHODS AND RESULTS: In patients
      scheduled for heart catheterisation, minimal lumen diameter (MLD) and diameter
      derived percent stenosis (DPS) were obtained for CAS (>50%) using both QCA and
      the 3D-system. To estimate stenosis length, a non-inflated balloon was inserted
      into the stenosis and the distance between balloon markers was measured using
      both methods and then compared to the known distance between the markers. In 61
      patients 79 lesions were analysed. MLD measurements showed a good agreement
      between QCA and 3D with a mean difference of 0.08+/-0.035 mm. Reference diameter
      was 2.61+/-0.67 for 3D and 2.42+/-0.61 mm for QCA and 54.79+/-9.20% vs. 58.75+/
      8.15% for the %-stenosis range, respectively. The mean true balloon length was
      12.8 mm+/-3.8 mm. Lengths determined by the 3D system were 13.0+/-4.0 mm and
      11.3+/-3.8 mm by QCA, respectively. CONCLUSIONS: Evaluation of CAS using the
      novel 3D system was feasible and showed equivalent results to validated QCA
      measurements. Length measurements seemed to be more accurate by the 3D system as
      compared to QCA. Therefore, this 3D-system can be used to guide decisions in
      interventional cardiology.

PMID- 19577996
TI  - Porcine models of coronary atherosclerosis and vulnerable plaque for imaging and
      interventional research.
AB  - Animal models facilitate our understanding of human disease by providing a
      controlled environment permitting testing of mechanisms of disease, diagnostic
      technologies and therapeutic interventions. The ideal animal model should display
      coronary lesions resembling those seen in human atherosclerosis. No suitable
      large animal model of high-risk (vulnerable) plaque exists. Lack of such a model
      has hampered studies designed to validate imaging technologies and to scrutinise
      the effects of therapeutic interventions in atherosclerotic arteries. Several
      porcine models of advanced human-like coronary atherosclerosis exist. In this
      review some of the most promising porcine models are discussed, focusing on their
      applicability in the development and validation of coronary imaging technologies
      and interventional devices. In the evolving era of technological development, the
      availability and use of such animal models of advanced human-like coronary
      atherosclerosis and vulnerable plaque will become critically important in the
      preclinical testing of emerging technologies in interventional cardiology.

PMID- 19577998
TI  - Coating irregularities of durable polymer-based drug-eluting stents as assessed
      by scanning electron microscopy.
AB  - AIMS: To classify and quantify post-expansion irregularities in durable polymer
      based coatings of drug-eluting stents (DES). METHODS AND RESULTS: Taxus Liberte,
      Endeavor Sprint, Endeavor Resolute and Xience V DES (three samples of each) were
      explored by light microscopy and scanning electron microscopy (SEM) following
      expansion at 14 atm in water. Incidence and size of irregularities were measured
      during thorough quantitative examinations of a 360 SEM images. DES types examined
      showed a significant difference in the incidence of irregularities (p<0.0001;
      6.6+/-4.2/image at 60-fold magnification) with typical patterns specific for each
      DES. All types showed areas with bare metal-aspects, but incidence, shape, and
      size differed largely: Sprint showed the largest areas. Cracks were only found in
      Sprint and Resolute, while wrinkles were seen exclusively in Taxus Liberte and
      Xience V (p<0.0001). The coating of each DES type showed some inhomogeneity of
      distribution, but the incidence differed (p<0.0001) and was least in Taxus
      Liberte, which, on the other hand, was the only DES that showed webbing with
      large bare-metal exposure. CONCLUSIONS: The incidence and size of various coating
      irregularities on different types of DES varied widely. These data may be
      considered in ongoing discussions on the differences between DES and may serve as
      reference to compare novel DES.

PMID- 19577997
TI  - Validation of in vivo plaque characterisation by virtual histology in a rabbit
      model of atherosclerosis.
AB  - AIMS: Most acute coronary syndromes are caused by plaque rupture. The risk of
      plaque rupture is related to plaque composition. The purpose of this study was to
      validate VH-IVUS for in vivo plaque characterisation. METHODS AND RESULTS: Six
      rabbits were fed a cholesterol-supplemented diet for 12 to 18 months. Thereafter,
      VH-IVUS imaging of the aorta was performed. After sacrifice, the VH-IVUS images
      were matched to the corresponding histological cross sections. A total of 260
      atherosclerotic plaques were analysed. VH-IVUS had a high sensitivity,
      specificity and positive predictive value for the detection of non-calcified thin
      cap fibroatheroma (88%, 96%, 87%, respectively) and calcified thin cap
      fibroatheroma (95%, 99%, 93%, respectively). These values were respectively 82%,
      94%, 85% for non-calcified fibroatheroma and 78%, 98%, 84% for calcified
      fibroatheroma. The lowest values were obtained for pathological intimal
      thickening (74%, 92%, 70%, respectively). For all plaque types, VH-IVUS had a
      kappa-value of 0.79. Linear regression analysis and Bland-Altman plots showed a
      strong correlation between VH-IVUS and histology for fibrous tissue, fibrofatty
      tissue, necrotic calcified tissue and confluent necrotic core. CONCLUSIONS: VH
      IVUS showed a good accuracy for in vivo plaque characterisation and is a
      promising technique for the detection of the vulnerable plaque.

PMID- 19577999
TI  - Multifocal arterial fibromuscular dysplasia causing coronary artery dissection
      following coronary angiography.

PMID- 19578002
TI  - Antiplatelet medications in hemodialysis patients: a systematic review of
      bleeding rates.
AB  - BACKGROUND AND OBJECTIVES: Patients with end stage renal disease (ESRD) are often
      prescribed antiplatelet medications. However, these patients are also at
      increased risk of bleeding compared with the general population, and an aim was
      made to quantify this risk with antiplatelet agents. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A systematic review of the literature (Medline,
      EMBASE, Cochrane CENTRAL and Google Scholar databases) was done to determine the
      bleeding risk in ESRD patients prescribed antiplatelet therapy. The secondary
      outcome was the effect on access thrombosis. All case series, cohort studies and
      clinical trials were considered if they included ten or more ESRD patients,
      assessed bleeding risk with antiplatelet agents, and lasted for more than 3 mo.
      RESULTS: Sixteen studies, including 40,676 patients, were identified that met
      predefined inclusion criteria. Due to study heterogeneity and weaknesses in
      methodology, bleeding rates were not pooled across studies. However, the bleeding
      risk appears to be increased for hemodialysis patients treated with combination
      antiplatelet therapy. The results are mixed for studies using a single
      antiplatelet agent. Antiplatelet agents appear to be effective in preventing
      shunt and central venous catheter thrombosis, but not for preventing thrombosis
      of arteriovenous grafts. CONCLUSION: The risks and benefits of antiplatelet
      agents in ESRD patients remain poorly defined. Until a clinical trial addresses
      this in the dialysis population, individual risk stratification taking into
      account the increased risk of bleeding should be considered before initiating
      antiplatelet agents, especially in combination therapy.

PMID- 19578003
TI  - Calcium, parathyroid hormone, and vitamin D: major determinants of chronic pain
      in hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Pain is a frequent complaint of hemodialysis (HD)
      patients, yet information regarding its causes and frequency is relatively
      scarce. The aim of this study was to evaluate the frequency and possible causes
      of chronic pain in patients who are on long-term HD. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We prospectively enrolled 100 patients who were
      undergoing maintenance HD for at least 3 mo. Pain was evaluated using the Brief
      Pain Inventory. Data collected on each participant included age, gender, ethnic
      origin, body mass index, smoking habits, time on dialysis, type of blood access,
      comorbidities, and biochemical and hematologic parameters. RESULTS: The average
      age was 64.5 yr; the average time on dialysis 40.4 mo. Forty-five patients were
      male. Thirty-one participants were of Arabic origin. Fifty-three patients had
      diabetes, 36 of whom had diabetic retinopathy. Although 51 patients experienced
      chronic pain, only 19.6% described the pain as severe. Musculoskeletal pain,
      neuropathic pain, and headache were the most prevalent forms of pain. The
      presence of diabetic retinopathy and neuropathy (but not diabetes per se) and
      levels of intact parathyroid hormone, calcium, and calcitriol (but not 25
      hydroxyvitamin D(3)) differed significantly between those who experienced chronic
      pain and those who did not. On a logistic regression model, higher serum calcium
      levels and intact parathyroid hormone levels >250 pg/ml were independently
      associated with chronic pain, as well as the presence of diabetic retinopathy.
      Calcitriol had a marginal effect. CONCLUSIONS: Disturbed mineral metabolism is
      strongly associated with chronic pain in long-term HD patients, along with
      microangiopathy.

PMID- 19578004
TI  - Rituximab treatment of adult patients with steroid-resistant focal segmental
      glomerulosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Isolated case reports have shown a beneficial effect
      of rituximab on pediatric patients with primary FSGS, but there is no information
      about rituximab treatment of FSGS in adults. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: All patients who had biopsy-proven FSGS and were treated with
      rituximab in Spain were identified, independent of their positive or negative
      response, among the nephrology departments that belong to the Spanish Group for
      the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome
      after rituximab treatment were studied. RESULTS: Eight patients were identified.
      Rituximab failed to improve nephrotic syndrome in five of eight patients, who
      continued to show massive proteinuria and exhibited a rapidly deteriorating renal
      function in two cases. Among the remaining three patients, two of them showed an
      improvement of renal function and a remarkable proteinuria reduction and one
      experienced a beneficial but transitory effect after rituximab. There were no
      differences in clinical or laboratory characteristics or in the CD20 B lymphocyte
      count after rituximab between these three patients and the five who had a
      negative response. The only difference was in the regimen of rituximab
      administration: Whereas the five patients with a negative response received only
      four weekly consecutive infusions of 375 mg/m(2), the three remaining patients
      received additional doses of rituximab. CONCLUSIONS: Only a minority (three of
      eight) of patients in our series of adult patients with FSGS showed a positive
      influence of rituximab. More studies are necessary to characterize further the
      optimal dosages and the mechanisms of action of rituximab in FSGS.

PMID- 19578005
TI  - Does idiopathic hypercalciuria trigger calcium-sensing receptor-mediated
      protection from urinary supersaturation?

PMID- 19578006
TI  - Podocyte glutamatergic signaling contributes to the function of the glomerular
      filtration barrier.
AB  - Podocytes possess the complete machinery for glutamatergic signaling, raising the
      possibility that neuron-like signaling contributes to glomerular function. To
      test this, we studied mice and cells lacking Rab3A, a small GTPase that regulates
      glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-d
      aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of
      Rab3A and blockade of NMDAR both associated with an increased urinary
      albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of
      ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A
      null podocytes displayed a dysregulated release of glutamate with higher rates of
      spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in
      freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism
      led to profound cytoskeletal remodeling and redistribution of nephrin in cultured
      podocytes; the addition of the agonist NMDA reversed these changes. In summary,
      these results suggest that glutamatergic signaling driven by podocytes
      contributes to the integrity of the glomerular filtration barrier and that
      derangements in this signaling may lead to proteinuric renal diseases.

PMID- 19578008
TI  - The role of podocalyxin in health and disease.
AB  - Podocalyxin, a sialomucin most closely related to CD34 and endoglycan, is
      expressed by kidney podocytes, hematopoietic progenitors, vascular endothelia,
      and a subset of neurons; aberrant expression has recently been implicated in a
      range of cancers. Through interactions with several intracellular proteins and at
      least one extracellular ligand, podocalyxin regulates both adhesion and cell
      morphology. In the developing kidney, podocalyxin plays an essential role in the
      formation and maintenance of podocyte foot processes, and its absence results in
      perinatal lethality. Podocalyxin expression in the hematopoietic system
      correlates with cell migration and the seeding of new hematopoietic tissues. In
      addition, it is abnormally expressed in subsets of breast, prostate, liver,
      pancreatic, and kidney cancer as well as leukemia. Strikingly, it is often
      associated with the most aggressive cases, and it is likely involved in
      metastasis. Thus, a thorough investigation of the normal activities of
      podocalyxin may facilitate the development of new cancer treatment strategies.

PMID- 19578007
TI  - Pirfenidone is renoprotective in diabetic kidney disease.
AB  - Although several interventions slow the progression of diabetic nephropathy,
      current therapies do not halt progression completely. Recent preclinical studies
      suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the
      mechanisms underlying its antifibrotic action are incompletely understood. Here,
      we evaluated the role of PFD in regulation of the extracellular matrix. In mouse
      mesangial cells, PFD decreased TGF-beta promoter activity, reduced TGF-beta
      protein secretion, and inhibited TGF-beta-induced Smad2-phosphorylation, 3TP-lux
      promoter activity, and generation of reactive oxygen species. To explore the
      therapeutic potential of PFD, we administered PFD to 17-wk-old db/db mice for 4
      wk. PFD treatment significantly reduced mesangial matrix expansion and expression
      of renal matrix genes but did not affect albuminuria. Using liquid chromatography
      with subsequent electrospray ionization tandem mass spectrometry, we identified
      21 proteins unique to PFD-treated diabetic kidneys. Analysis of gene ontology and
      protein-protein interactions of these proteins suggested that PFD may regulate
      RNA processing. Immunoblotting demonstrated that PFD promotes dosage-dependent
      dephosphorylation of eukaryotic initiation factor, potentially inhibiting
      translation of mRNA. In conclusion, PFD is renoprotective in diabetic kidney
      disease and may exert its antifibrotic effects, in part, via inhibiting RNA
      processing.

PMID- 19578010
TI  - Suppression of ICAM-1 in retinal and choroidal endothelial cells by plasmid small
      interfering RNAs in vivo.
AB  - PURPOSE: Leukocytes play a critical role in ocular diseases such as uveitis,
      diabetic retinopathy, and choroidal neovascularization. Intercellular adhesion
      molecule (ICAM)-1 is essential for the migration of leukocytes. Control of ICAM-1
      expression may lead to therapies for these diseases. Small-interfering
      ribonucleic acids (siRNAs) are efficient specific modulators of endogenous gene
      expression. The authors describe the application of siRNA to suppress ICAM-1
      expression on the murine neurosensory retina or retinal pigment epithelial (RPE)
      cells using a hydrodynamics-based transfection technique (HT) and intravitreal
      injection (IV) in vivo. METHODS: ICAM-1-specific plasmid siRNAs designed from the
      murine gene sequence were transfected into the retina using HT and IV in vivo.
      Green fluorescent protein (GFP) expression plasmid vector is used as a
      transfection marker in the retinal cells. ICAM-1 expression was analyzed by
      enzyme-linked immunosorbent assay and flow cytometry. ICAM-1 upregulation was
      induced by retinal laser photocoagulation and streptozotocin (STZ). RESULTS:
      After the administration of GFP expression plasmid with HT and IV, histologic
      analysis showed GFP fluorescence in every layer of the murine retina. After
      photocoagulation, ICAM-1 expression in the neurosensory retina or RPE cells
      transferred with plasmid ICAM-1 siRNA was significantly decreased compared with
      cells that were not transfected or cells transferred with scrambled control
      siRNA. Plasmid siRNAs silenced ICAM-1 expression after STZ administration
      compared with control or naked siRNA injection. CONCLUSIONS: SiRNA expression
      mediated by this plasmid causes efficient and specific downregulation of ICAM-1
      expression, suggesting that it can be silenced by plasmid siRNA in murine retina
      in vivo. This technology may lead to novel concepts to reduce retinal neovascular
      disease by inhibiting leukocyte infiltration.

PMID- 19578009
TI  - Nitric oxide inhibits glomerular TGF-beta signaling via SMOC-1.
AB  - Cytokines and nitric oxide (NO) stimulate rat mesangial cells to synthesize and
      secrete inflammatory mediators. To understand better the signaling pathways that
      contribute to this response, we exposed rat mesangial cells to the prototypic
      inflammatory cytokine IL-1beta and analyzed the changes in the pattern of gene
      expression. IL-1beta downregulated the gene encoding the matricellular
      glycoprotein secreted modular calcium-binding protein 1 (SMOC-1) in mesangial
      cells. Inflammatory cytokines attenuated SMOC-1 mRNA and protein expression
      through endogenous production of NO, which activated the soluble guanylyl
      cyclase. Silencing SMOC-1 expression with small interfering RNA decreased the
      formation of TGF-beta, reduced SMAD binding to DNA, and decreased mRNA expression
      of genes regulated by TGF-beta. In a rat model of anti-Thy-1 glomerulonephritis,
      glomerular SMOC-1 mRNA and protein decreased and inducible NO synthase expression
      increased simultaneously. Treatment of nephritic rats with the inducible NO
      synthase-specific inhibitor l-N(6)-(1-iminoethyl)-lysine prevented SMOC-1
      downregulation. In summary, these data suggest that NO attenuates SMOC-1
      expression in acute glomerular inflammation, thereby limiting TGF-beta-mediated
      profibrotic signaling.

PMID- 19578011
TI  - Comparison of the histology, gene expression profile, and phenotype of cultured
      human limbal epithelial cells from different limbal regions.
AB  - PURPOSE: To investigate whether human limbal epithelial cells (HLECs) derived
      from various regions of the limbus exhibit differences in gene expression and
      epithelial characteristics. METHODS: HLECs were derived from explants taken from
      the superior, nasal, inferior, and temporal limbus and cultured for 21 days.
      Whole genome transcript profiling was performed with a gene microarray. The
      microarray results were validated by using RT-PCR. Epithelial morphology was
      studied with light microscopy and transmission electron microscopy, and phenotype
      was evaluated by immunohistochemistry. RESULTS: Epithelial outgrowth was present
      in most cultures of superior origin (88%) in contrast to cultures of temporal
      origin (38%). The epithelial thickness and number of cell layers were
      significantly greater in cultures of superior origin than in cultures from
      inferior and temporal areas. TRIM36, OSR2, and RHOU, which are involved in
      morphogenesis, were significantly differentially expressed in the superior
      region, compared with the other regions. Proposed limbal stem cell, progenitor,
      and differentiation markers were not differentially expressed. The uniform gene
      expression of ocular surface markers correlated with homogeneous immunostaining
      of corresponding protein markers in HLEC cultures from all regions, demonstrating
      an undifferentiated phenotype (p63(+), DeltaNp63alpha(+), ABCG2(+), K19(+),
      vimentin(+), integrin beta1(+), nestin(-), K3(-), K5(+), and E-cadherin(+)).
      CONCLUSIONS: No major transcriptional or phenotypic differences were observed in
      cultured HLECs derived from different regions of the limbus. However, explants of
      superior origin demonstrated the highest outgrowth success rate and generated
      epithelia with greater epithelial thickness and number of cell layers, which may
      prove useful for transplantation purposes.

PMID- 19578012
TI  - Mitochondrial proteomics in experimental autoimmune uveitis oxidative stress.
AB  - PURPOSE: Photoreceptor mitochondrial oxidative stress is the initial pathologic
      event in experimental autoimmune uveitis. In this study, the authors determined
      alterations in retinal mitochondrial protein levels in response to oxidative
      stress during the early phase of experimental autoimmune uveitis (EAU). METHODS:
      Retinal mitochondrial fractions during early EAU were prepared and subjected to
      two-dimensional difference in gel electrophoresis (2D-DIGE). Protein spots
      showing differential expression were excised and subjected to matrix-assisted
      laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) for
      peptide identification. Levels of these proteins were also confirmed by Western
      blot analysis. mRNA expression of these proteins was confirmed by real-time PCR.
      TUNEL staining was performed to detect apoptosis. RESULTS: 2D-DIGE analysis
      revealed differential expression of 13 proteins. Ten proteins were overexpressed,
      including manganese-SOD, alphaA crystallin, beta crystallin, and four proteins
      were downregulated, including adenosine triphosphate (ATP) synthase, malate
      dehydrogenase, and calretinin. Increased levels of alphaA crystallin, betaB2
      crystallin, MnSOD, and aconitase and decreased levels of ATP synthase were
      confirmed by Western blot analysis. qPCR also confirmed the increased expression
      of alphaA crystallin, betaB2 crystallin, MnSOD, and Hsp70. Apoptosis was absent
      during this phase. CONCLUSIONS: The presence of mitochondrial-specific oxidative
      stress-related proteins in the early EAU retina along with the downregulation of
      ATP synthase provides early evidence of stress-related retinal damage. The
      presence of high levels of alphaA and betaB2 crystallin in the mitochondria may
      prevent cell death during early EAU.

PMID- 19578013
TI  - Neuronal activity influences hemodynamics in the paraoptic short posterior
      ciliary arteries: a comparison between healthy and glaucomatous subjects.
AB  - PURPOSE: Perfusion of the retina adapts to metabolic demand by neurovascular
      coupling. The present study was an investigation of the presence of neurovascular
      coupling in the anterior part of the optic nerve in healthy subjects and patients
      with glaucoma. METHODS: Retrobulbar blood flow velocities were determined by
      color Doppler imaging (CDI). Peak systolic and end diastolic velocities (PSVs and
      EDVs) in the central retinal artery (CRA) or the short posterior ciliary artery
      (SPCA) were the primary readout. CDI measurements were performed shortly before,
      during, immediately after, 60 seconds after, and 120 seconds after a 10-Hz
      flicker stimulation of the retina. RESULTS: Thirty-five patients with glaucoma
      and 44 healthy control subjects were included in the study. In the SPCA of
      healthy control subjects, flicker stimulation led to an increase in PSV from 9.7
      +/- 0.8 to 12.5 +/- 0.8 cm/s (P < 0.001; n = 24) and of EDV from 2.4 +/- 0.3 to
      3.6 +/- 0.3 cm/s (P < 0.001; n = 24). This effect was not detectable in patients
      with glaucoma. In the CRA, flicker light led to an increase in EDV from 2.1 +/-
      0.2 to 3.0 +/- 0.3 cm/s (P = 0.002; n = 20) in healthy volunteers and from 1.3 +/
      0.2 to 2.0 +/- 0.2 cm/s in patients with glaucoma (P = 0.004; n = 15). PSV was
      not affected by flicker stimulation in either the healthy volunteers or patients
      with glaucoma. CONCLUSIONS: The data indicate the presence of neurovascular
      coupling in the vascular bed supplied by the paraoptic SPCA. The response pattern
      to the flicker stimulus differs between healthy subjects and individuals with
      glaucoma.

PMID- 19578014
TI  - Increased hypoxia following vessel targeting in a murine model of retinoblastoma.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of vessel
      targeting and chemotherapy agents on inducing hypoxic regions in LH(BETA)T(AG)
      murine retinal tumors. METHODS. Twelve- and 16-week-old LH(BETA)T(AG) transgenic
      retinoblastoma mice were treated with periocular injections to the right eye only
      of saline (n = 42), anecortave acetate (a single injection; 300 microg/20 microL;
      n = 42), or carboplatin (two injections per week for 3 weeks; 62.5 microg/20
      microL; n = 42). Eyes were enucleated 1 day, 1 week, and 1 month after injection.
      To assess hypoxia, mice received 60 mg/kg pimonidazole via intraperitoneal
      injection. Eyes were enucleated, and tumor sections were analyzed. RESULTS:
      Levels of hypoxia significantly increase in 16-week-old animals 1 day and 1 week
      after treatment with anecortave acetate, a known angiostatic agent. Eyes treated
      with anecortave acetate showed a 28% (P < 0.001) increase in hypoxic regions in
      comparison with the saline-treated control group 1 day after injection and a 17%
      (P < 0.001) increase 1 week after injection. In early tumors of 12-week-old
      animals, levels of hypoxia increased by 2.0% (P = 0.011) 1 day after anecortave
      acetate injection compared to controls. Levels of hypoxia significantly decrease
      in 16-week-old animals 1 week and 1 month after treatment with carboplatin, a
      chemotherapeutic agent. Eyes treated with carboplatin showed a 21.7% (P = 0.017)
      decrease in hypoxic regions in comparison with the saline-treated control group 1
      week after injection and a 4.51% (P < 0.001) decrease 1 month after injection. In
      early tumors of 12-week-old animals, levels of hypoxia decreased by 0.0429% (P <
      0.001) 1 month after carboplatin injection compared with controls. CONCLUSIONS:
      Treatment with a vessel-targeting agent results in changes in the tumor
      microenvironment as early as 1 day after treatment. By increasing hypoxia in
      tumors, vessel-targeting agents can be combined with glycolytic inhibitors which
      have been shown previously to target hypoxic regions in this transgenic model.
      This approach may have benefits for children with this disease and should be
      further investigated.

PMID- 19578015
TI  - Study of gene-targeted mouse models of splicing factor gene Prpf31 implicated in
      human autosomal dominant retinitis pigmentosa (RP).
AB  - PURPOSE: Pre-mRNA processing factor 31 (PRPF31) is a ubiquitous protein needed
      for the assembly of the pre-mRNA splicing machinery. It has been shown that
      mutations in this gene cause autosomal dominant retinitis pigmentosa 11 (RP11),
      which is characterized by rod-cell degeneration. Interestingly, mutations in this
      ubiquitously expressed gene do not lead to phenotypes other than retinal
      malfunction. Furthermore, the dominant inheritance pattern has shown incomplete
      penetrance, which poses interesting questions about the disease mechanism of
      RP11. METHODS: To characterize PRPF31 function in the rod cells, two animal
      models have been generated. One was a heterozygous knock-in mouse
      (Prpf31(A216P/+)) carrying a point mutation p.A216P, which has previously been
      identified in RP11 patients. The second was a heterozygous knockout mouse
      (Prpf31(+/-)). Retinal degeneration in RP11 mouse models was monitored by
      electroretinography and histology. RESULTS: Generation of the mouse models is
      presented, as are results of ERGs and retinal morphology. No degenerative
      phenotype on fundus examination was found in Prpf31(A216P/+) and Prpf31(+/-)
      mice. Prpf31(A216P/A216P) and Prpf31(-/-) genotypes were embryonic lethal.
      CONCLUSIONS: The results imply that Prpf31 is necessary for survival, and there
      is no compensation mechanism in mouse for the lack of this splicing factor. The
      authors suggest that p.A216P mutation in Prpf31 does not exert a dominant
      negative effect and that one Prpf31 wild-type allele is sufficient for
      maintenance of the healthy retina in mice.

PMID- 19578016
TI  - The natural history of stargardt disease with specific sequence mutation in the
      ABCA4 gene.
AB  - PURPOSE: To determine longitudinal changes in fundus appearance and visual
      function in patients with Stargardt with at least one allelic mutation
      (Gly1961Glu) in the ABCA4 gene. METHODS: Sixteen patients with a diagnosis of
      Stargardt disease and a Gly1961Glu mutation were enrolled. All patients underwent
      a complete ocular examination including best corrected visual acuity, Goldmann
      visual field (GVF), and full-field ERG examinations. The percentage of patients
      who showed at least a doubling in the log of the minimum angle of visual
      resolution (logMAR) between their initial and most recent visits was determined,
      as was the percentage of patients who showed a doubling in the size of the
      central scotoma over this duration. RESULTS: Nine patients had at least a
      doubling of the logMAR visual acuity in their right eyes and 10 patients in their
      left eyes, over a mean follow-up (FU) period of 18.6 years. Of 15 patients, 46.7%
      had equal to or more than a doubling of the central scotoma area in response to a
      II2e test stimulus in the right eye and 60.0% in the left eyes. Among 10 patients
      whose ERGs were initially normal for rod and cone responses, 8 remained normal at
      their most recent FU visit. CONCLUSIONS: In these patients with Stargardt disease
      and a Gly1961Glu mutation, most showed a clinical phenotype characterized by
      fundus changes localized to the foveal and parafoveal regions, normal ERG
      amplitudes, absence of a silent or masked choroid, and a mean age at initial
      presentation in the third decade.

PMID- 19578017
TI  - Comparison between macular pigment optical density measurements using two
      wavelength autofluorescence and heterochromatic flicker photometry techniques.
AB  - PURPOSE: The association of macular pigment (MP) with age-related macular
      degeneration has been extensively studied in recent years, and interest in a
      rapid, objective, and accurate technique to measure MP optical density (MPOD) has
      increased. The purpose of this study was to compare the MPOD values at specific
      loci around the fovea using the heterochromatic flicker photometry (HFP) and the
      two-wavelength autofluorescence (AF) methods in a young, healthy population.
      METHODS: Ten patients (20 eyes) were enrolled. Subjects with any ocular or
      systemic disease were excluded. All patients underwent HFP and AF examination.
      The AF examination was performed using a modified scanning laser ophthalmoscope.
      Values for both devices were measured at four eccentricities around the fovea
      (0.25 degrees , 0.5 degrees, 1.0 degrees, and 1.75 degrees). Each eye was tested
      three times with each METHOD: Statistical analysis was based on paired t-test and
      linear regression analysis. RESULTS: At all retinal eccentricities, the HFP
      values were consistently lower than the HRA values (P < 0.001). There was,
      however, a significant correlation at almost all locations. The strongest
      correlation between two methods was found at 1.75 degrees from the center of the
      fovea (r = 0.73). CONCLUSIONS: The modified-HRA AF method for MPOD generated
      results that were highly correlated with the standard HPF method but consistently
      higher at all eccentricities. These findings suggest that HRA can be reliably
      used in patients unable to perform HPF, which is important for wider clinical
      application of MP testing.

PMID- 19578018
TI  - Metamorphopsia assessment before and after vitrectomy for macular hole.
AB  - PURPOSE: To evaluate the degree of metamorphopsia in 42 patients before and 6
      months after vitrectomy for idiopathic unilateral macular hole. METHODS:
      Semicircular test and reference stimuli of variable diameters were applied in a
      binocular test that measured interocular size disparity in patients with
      unilateral macular hole. The test was applied 1 day before surgery and repeated
      after 6 months. RESULTS: Before surgery, mean disparity was 0.34 degrees at 1
      degrees visual field eccentricity declining to a plateau value of approximately
      0.2 degrees between 3 degrees and 5 degrees of eccentricity. Six months after
      successful hole closure, interocular disparity was practically constant, with a
      median disparity below 0.1 and no significant effect of eccentricity. Baseline
      interocular disparities lower than 0.35 degrees at 1 degrees eccentricity were
      associated with nine EDTRS letters of better visual outcome compared with higher
      disparities (P < 0.001). CONCLUSIONS: Metamorphopsia was consistently reduced
      after macular hole surgery, supporting that the intervention was successful in
      repositioning displaced photoreceptors toward their original location. Final best
      corrected visual acuity was related to the degree of preoperative disparity in
      spatial projection between receptive units with a shared perceptual projection in
      visual space in the two eyes. (ClinicalTrials.gov number, NCT00302328.).

PMID- 19578019
TI  - In vivo imaging of microscopic structures in the rat retina.
AB  - PURPOSE: The ability to resolve single retinal cells in rodents in vivo has
      applications in rodent models of the visual system and retinal disease. The
      authors have characterized the performance of a fluorescence adaptive optics
      scanning laser ophthalmoscope (fAOSLO) that provides cellular and subcellular
      imaging of rat retina in vivo. METHODS: Enhanced green fluorescent protein (eGFP)
      was expressed in retinal ganglion cells of normal Sprague-Dawley rats via
      intravitreal injections of adeno-associated viral vectors. Simultaneous
      reflectance and fluorescence retinal images were acquired using the fAOSLO.
      fAOSLO resolution was characterized by comparing in vivo images with subsequent
      imaging of retinal sections from the same eyes using confocal microscopy.
      RESULTS: Retinal capillaries and eGFP-labeled ganglion cell bodies, dendrites,
      and axons were clearly resolved in vivo with adaptive optics. Adaptive optics
      correction reduced the total root mean square wavefront error, on average, from
      0.30 microm to 0.05 microm (measured at 904 nm, 1.7-mm pupil). The full width at
      half maximum (FWHM) of the average in vivo line-spread function (LSF) was
      approximately 1.84 microm, approximately 82% greater than the FWHM of the
      diffraction-limited LSF. CONCLUSIONS: With perfect aberration compensation, the
      in vivo resolution in the rat eye could be approximately 2x greater than that in
      the human eye because of its large numerical aperture (approximately 0.43).
      Although the fAOSLO corrects a substantial fraction of the rat eye's aberrations,
      direct measurements of retinal image quality reveal some blur beyond that
      expected from diffraction. Nonetheless, subcellular features can be resolved,
      offering promise for using adaptive optics to investigate the rodent eye in vivo
      with high resolution.

PMID- 19578020
TI  - Morphologic indication for proprioception in the human ciliary muscle.
AB  - PURPOSE: To search for proprioceptive nerve terminals in human ciliary muscle.
      METHODS: In 48 human donor eyes, histologic and ultrathin sections cut in
      different planes and wholemounts of the ciliary muscle were studied.
      Immunohistochemical staining with antibodies against pan-neuronal antigens and
      antigens reported as markers for sensory terminals in other organs was performed.
      RESULTS: Among the markers for proprioceptive terminals, only calretinin was
      present in the ciliary body. Calretinin-immunoreactive (IR) nerve terminals
      surrounded the posterior and reticular ciliary muscle tips and their elastic
      tendons. Terminals in that region contained mitochondria and neurofilaments. At
      the anterior tips larger terminals with numerous membrane-filled vesicles were
      located between the muscle fibers. The most elaborate network of calretinin-IR
      nerve fibers was present in the ground plate covering the circular muscle
      portion. Here calretinin-IR neurons with morphologic features of mechanoreception
      were present. Within the circular muscle portion numerous calretinin-IR ganglion
      cells were found. Their processes were connected to the calretinin-IR network but
      also surrounded ciliary muscle cells and NADPH-diaphorase-positive ganglion
      cells. CONCLUSIONS: These morphologic findings indicate that there are
      proprioreceptors in the ciliary muscle that morphologically and presumably
      functionally differ at different locations. At the posterior muscle tips, the
      receptors could measure stretch of the tendons, whereas the large receptor organs
      located at the anterior muscle tips morphologically resemble mechanoreceptors
      measuring shear stress. The presence of the numerous intrinsic nerve cells
      indicates that contraction of the circular muscle portion can be modulated
      locally via a self-contained reflex arc.

PMID- 19578021
TI  - Pro-photoreceptor activity of chick neurogenin1.
AB  - PURPOSE: Better understanding of photoreceptor fate specification may lead to
      efficient production of photoreceptors for cell replacement studies. The authors
      investigated the role of proneural bHLH gene neurogenin1 (ngn1) in photoreceptor
      genesis using the chick retina. METHODS: In situ hybridization was used to
      delineate the spatial and temporal pattern of ngn1 expression. RCAS retrovirus
      was used to drive overexpression of ngn1 in retinal cells, and siRNA was used to
      reduce ngn1 expression in loss-of-function experiments. RESULTS: Chick ngn1 was
      transiently expressed during early phases of retinal neurogenesis, from embryonic
      day (E)3 to E6, with cells expressing ngn1 confined to the apical side of the
      retinal neuroepithelium. The time window and the anatomic location of ngn1
      expression coincided with photoreceptor genesis and differed from those of other
      transiently expressed proneural bHLH genes, such as ash1, ath3, ath5, and ngn2.
      Most ngn1-expressing cells lacked BrdU incorporation and lacked phosphorylated
      histone H3. In low-density cell culture, ngn1 overexpression increased neuroD
      expression and expanded the photoreceptor population but reduced the ganglion
      population. Treatment of dissociated retinal cells with siRNA against ngn1 mRNA
      specifically reduced the photoreceptor population. Overexpression of ngn1 in the
      retina reduced the expression of ash1, ath5, chx10, and ngn2. CONCLUSIONS: The
      data suggest that ngn1 participates in a complex transcriptional network and may
      play a role in guiding a progenitor cell to the photoreceptor pathway.

PMID- 19578022
TI  - The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated
      accumulation of swollen autofluorescent subretinal macrophages.
AB  - PURPOSE: Drusen, which are defined clinically as yellowish white spots in the
      outer retina, are cardinal features of age-related macular degeneration (AMD).
      Ccl2-knockout (Ccl2(-/-)) mice have been reported to develop drusen and
      phenotypic features similar to AMD, including an increased susceptibility to
      choroidal neovascularization (CNV). This study was conducted to investigate the
      nature of the drusenlike lesions in vivo and further evaluate the Ccl2(-/-) mouse
      as a model of AMD. METHODS: The eyes of 2- to 25-month-old Ccl2(-/-) and C57Bl/6
      mice were examined in vivo by autofluorescence scanning laser ophthalmoscopy (AF
      SLO) and electroretinography, and the extent of laser-induced CNV was measured by
      fluorescein fundus angiography. The retinal morphology was also assessed by
      immunohistochemistry and quantitative histologic and ultrastructural morphometry.
      RESULTS: The drusenlike lesions of Ccl2(-/-) mice comprised accelerated
      accumulation of swollen CD68(+), F4/80(+) macrophages in the subretinal space
      that were apparent as autofluorescent foci on AF-SLO. These macrophages contained
      pigment granules and phagosomes with outer segment and lipofuscin inclusions that
      may account for their autofluorescence. Only age-related retinal pigment
      epithelium (RPE) damage, photoreceptor loss, and sub-RPE deposits were observed
      but, despite the accelerated accumulation of macrophages, we identified no
      spontaneous development of CNV in the senescent mice and found a reduced
      susceptibility to laser-induced CNV in the Ccl2(-/-) mice. CONCLUSIONS: These
      findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking
      defect during aging and to an impaired recruitment of these cells to sites of
      laser injury. Other, previously described features of Ccl2(-/-) mice that are
      similar to AMD may be the result of aging alone.

PMID- 19578024
TI  - Differential effects of TGFbeta and vitreous on the transformation of retinal
      pigment epithelial cells.
AB  - PURPOSE: In proliferative vitreoretinopathy retinal pigment epithelial (RPE)
      cells undergo epithelial-mesenchymal transformation (EMT). Vitreous and
      transforming growth factor-beta (TGFbeta) have been implicated in this EMT. The
      role of TGFbeta in the vitreous-mediated transformation of low-passage human RPE
      cells was investigated. METHODS: Cells were treated with vitreous or TGFbeta2.
      SB431542 was used to inhibit TGFbeta signaling. Morphology was investigated using
      phase-contrast or confocal microscopy. Motility was measured using a monolayer
      wounding assay. Invasion was determined using basement membrane matrix-based
      assays. Gene expression was measured by quantitative PCR, immunohistochemistry,
      or immunoblotting. RESULTS: Changes in phosphorylation or cellular localization
      of Smad -2, -3, or -4 indicated a TGFbeta-like activity in vitreous. Cortical
      actin filaments in untreated cells were replaced by stress fibers after TGFbeta
      treatment, but peripheral actin aggregates were seen in vitreous-treated cells.
      SB431542 did not block the morphologic change induced by vitreous. Vitreous
      treated cells exhibited increased motility and invasion, whereas TGFbeta-treated
      cells did not. However, SB431542 decreased vitreous-meditated changes in motility
      and invasion. The levels of mRNA for genes indicative of myofibroblast
      differentiation (alpha-SMA and CTGF) were increased by treatment with TGFbeta but
      suppressed by vitreous. TGFbeta or vitreous caused increased expression of
      Snail1. CONCLUSIONS: Vitreous or TGFbeta caused a fibroblast-like morphology and
      induced Snail1, a marker of EMT. TGFbeta activity in vitreous was necessary but
      not sufficient for the vitreous-induced motile, invasive phenotype. However,
      differences in the cytoskeletal organization and in the expression of CTGF and
      alpha-SMA suggested that TGFbeta-treatment caused differentiation along a
      myofibroblast pathway, whereas vitreous treatment suppressed myofibroblast
      formation.

PMID- 19578023
TI  - Genotyping microarray for CSNB-associated genes.
AB  - PURPOSE: Congenital stationary night blindness (CSNB) is a clinically and
      genetically heterogeneous retinal disease. Although electroretinographic (ERG)
      measurements can discriminate clinical subgroups, the identification of the
      underlying genetic defects has been complicated for CSNB because of genetic
      heterogeneity, the uncertainty about the mode of inheritance, and time-consuming
      and costly mutation scanning and direct sequencing approaches. METHODS: To
      overcome these challenges and to generate a time- and cost-efficient mutation
      screening tool, the authors developed a CSNB genotyping microarray with arrayed
      primer extension (APEX) technology. To cover as many mutations as possible, a
      comprehensive literature search was performed, and DNA samples from a cohort of
      patients with CSNB were first sequenced directly in known CSNB genes.
      Subsequently, oligonucleotides were designed representing 126 sequence variations
      in RHO, CABP4, CACNA1F, CACNA2D4, GNAT1, GRM6, NYX, PDE6B, and SAG and spotted on
      the chip. RESULTS: Direct sequencing of genes known to be associated with CSNB in
      the study cohort revealed 21 mutations (12 novel and 9 previously reported). The
      resultant microarray containing oligonucleotides, which allow to detect 126 known
      and novel mutations, was 100% effective in determining the expected sequence
      changes in all known samples assessed. In addition, investigation of 34 patients
      with CSNB who were previously not genotyped revealed sequence variants in 18%, of
      which 15% are thought to be disease-causing mutations. CONCLUSIONS: This
      relatively inexpensive first-pass genetic testing device for patients with a
      diagnosis of CSNB will improve molecular diagnostics and genetic counseling of
      patients and their families and gives the opportunity to analyze whether, for
      example, more progressive disorders such as cone or cone-rod dystrophies underlie
      the same gene defects.

PMID- 19578025
TI  - Toxicity assessment of intravitreal triamcinolone and bevacizumab in a retinal
      explant mouse model using two-photon microscopy.
AB  - PURPOSE: Intravitreal drug administration leads to high intraocular
      concentrations with potentially toxic effects on ocular tissues. This study was
      an assessment of the toxicity of triamcinolone and bevacizumab in living retinal
      explants using two-photon (2P) microscopy. METHODS: Wild-type mice received
      intravitreal injections of triamcinolone, bevacizumab, or vehicle. Ten and 45
      days after injection, wholemounted retinal explants were incubated with the
      fluorescent dye sulforhodamine 101 (SR101) to analyze morphology and tissue
      damage with 2P microscopy ex vivo. Retinas that received the same treatment were
      stained for apoptosis (TUNEL) and glial activation (GFAP). An intravitreal
      injection of NMDA (N-methyl-d-aspartate) was used as a positive control to ensure
      the fidelity of detection of retinal damage with ex vivo 2P microscopy. RESULTS:
      Overall retinal morphology was undisturbed after all procedures and time points.
      NMDA injection resulted in a strong increase in the number of SR101-labeled cells
      and increased apoptosis and glial activation when compared with sham-injected
      eyes. This result was in contrast to exposure to bevacizumab, which caused no
      appreciable damage. After triamcinolone treatment, marked damage in the inner
      retina was observed. However, damaged cells were restricted to sharply demarcated
      areas, and only mild changes in TUNEL-positive cells and GFAP activation was
      observed when compared to sham-injected eyes. CONCLUSIONS: 2P microscopy in
      combination with SR101 staining allows fast morphologic assessment of living
      retinal explants and can be used to evaluate adverse effects on retinal viability
      of test substances. Bevacizumab treatment did not cause any detectable retinal
      damage, whereas triamcinolone was associated with substantial, although spatially
      restricted, damage.

PMID- 19578026
TI  - Synergistic divergence: a distinct ocular motility dysinnervation pattern.
AB  - PURPOSE: To summarize the clinical, neuroradiologic, and genetic observations in
      a group of patients with unilateral synergistic divergence (SD). METHODS: Five
      unrelated patients with unilateral SD underwent ophthalmic and orthoptic
      examinations; three of them also had magnetic resonance imaging of the brain and
      orbits. Three patients underwent genetic evaluation of genes known to affect
      ocular motility: KIF21A, PHOX2A, HOXA1, and ROBO3. RESULTS: The patients did not
      meet the clinical criteria for CFEOM types 1, 2, or 3. Each patient had severe
      adduction weakness on the affected side and large-angle exotropia in primary gaze
      that increased on attempted contralateral gaze because of anomalous abduction.
      Magnetic resonance imaging revealed a much smaller medial rectus muscle in the
      involved SD orbit. Oculomotor cranial nerves were present in the one patient
      imaged appropriately. Genetic sequencing in three patients revealed no mutations
      in KIF21A, PHOX2A, HOXA1, or ROBO3. CONCLUSIONS: SD should be classified as a
      distinct congenital ocular motility pattern within congenital cranial
      dysinnervation disorders. It may be caused by denervation of the medial rectus
      with dysinnervation of the ipsilateral lateral rectus by the oculomotor nerve
      precipitated by genetic abnormalities (some currently identified) or by local
      environmental, teratogenic, or epigenetic disturbances.

PMID- 19578027
TI  - CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner
      retinopathy.
AB  - PURPOSE: To define the phenotype of the retinal degeneration associated with
      mutations in the CERKL gene. METHODS: Six patients (ages, 26-54 years) from three
      unrelated families with CERKL mutations were studied clinically and by
      electroretinography, kinetic, and chromatic static perimetry, autofluorescence
      (AF) imaging, and optical coherence tomography (OCT). RESULTS: Three siblings
      were homozygotes for p.R257X mutation; two siblings were compound heterozygotes
      for p.R257X and a novel p.C362X mutation; and one patient had only p.R257X
      mutation identified to date. There was a spectrum of severity: from mild visual
      acuity loss to light perception; from full kinetic fields with relative central
      scotomas to remnant peripheral islands; from reduced ERGs (some with negative
      waveforms) to nondetectable signals. Maculopathy showed residual foveal islands
      or extensive central rod and cone scotomas. With AF imaging, there was evidence
      of hyperautofluorescence at earlier and hypoautofluorescence at later disease
      stages. Peripheral function was generally less affected than central function.
      With OCT there were small foveal islands of outer nuclear layer (ONL) in those
      with preserved acuity. Eccentric to an annular region with no discernible ONL,
      there could be ONL in the midperiphery. At early disease stages, ganglion cell
      layer thickness was less affected than ONL. Later disease stages were accompanied
      by inner nuclear layer and nerve fiber layer abnormalities. CONCLUSIONS: CERKL
      mutations are associated with widespread retinal degeneration with prominent
      maculopathy. The clinical presentation is that of an autosomal recessive cone-rod
      dystrophy. Photoreceptor loss appears at all stages of disease and inner
      laminopathy complicates the phenotype at later stages.

PMID- 19578028
TI  - Reduced corneal thickness and enlarged anterior chamber in a novel ColVIIIa2G257D
      mutant mouse.
AB  - PURPOSE: The purpose of this study was the morphologic and genetic
      characterization of the novel eye size mutant Aca23 in the mouse. METHODS: The
      eyes of the mutants were characterized in vivo by optical low-coherence
      interferometry, Scheimpflug imaging, and funduscopy. Visual acuity was examined
      using a virtual optomotor system. Morphology was studied by histology, in situ
      hybridization, and immunohistochemistry. Linkage analysis was performed using
      genomewide scans with single nucleotide polymorphisms and microsatellite markers.
      RESULTS: Aca23 is a new semidominant eye size mutant that was discovered in an
      ENU mutagenesis screen. The phenotype includes increased anterior chamber depths,
      extended axial lengths, and reduced thickness of corneal layers. Aca23 was mapped
      to chromosome 4. A G-->A point mutation was identified at cDNA position 770 of
      Col8a2 encoding collagen VIII alpha2. The transition results in a G257D amino
      acid exchange affecting a highly conserved glycine residue in the collagenous
      domain. Proliferation of corneal endothelium, eye fundus, and visual acuity are
      not affected. CONCLUSIONS: The mouse mutant Aca23 described here offers the first
      point mutation of the Col8a2 gene in the mouse. The results of this study suggest
      that a functional collagen VIII alpha2 is essential for the correct assembly of
      the Descemet's membrane and for corneal stability. Aca23 might be used as a novel
      model for keratoglobus.

PMID- 19578029
TI  - From the margins to the center: ethnic minority women and the mental health
      effects of sexual assault.
AB  - The trauma of sexual assault is heightened for many women by the interlocking
      experience of societal traumas such as racism, sexism, and poverty. The mental
      health effects of sexual assault are mediated by race and ethnicity. The
      investigators explore the experiences of African American, Asian American,
      Latina, and Native American female survivors of sexual assault. The
      sociohistorical context of intergenerational trauma in the lives of ethnic
      minorities is a part of the context for the contemporary experience of sexualized
      violence. Racial and ethnic dynamics related to sexual assault prevalence, mental
      health effects, and disclosure are examined. Literature related to cultural
      beliefs, community attitudes, and perceived social support in relation to
      sexualized violence are also reviewed. Finally, practice, research, and policy
      implications are discussed.

PMID- 19578030
TI  - Genetic basis of aboveground productivity in two native Populus species and their
      hybrids.
AB  - Demonstration of genetic control over riparian tree productivity has major
      implications for responses of riparian systems to shifting environmental
      conditions and effects of genetics on ecosystems in general. We used field
      studies and common gardens, applying both molecular and quantitative techniques,
      to compare plot-level tree aboveground net primary productivity (ANPP(tree)) and
      individual tree growth rate constants in relation to plant genetic identity in
      two naturally occurring Populus tree species and their hybrids. In field
      comparisons of four cross types (Populus fremontii S. Wats., Populus angustifolia
      James, F(1) hybrids and backcross hybrids) across 11 natural stands, productivity
      was greatest for P. fremontii trees, followed by hybrids and lowest in P.
      angustifolia. A similar pattern was observed in four common gardens across a 290
      m elevation and 100 km environmental gradient. Despite a doubling in productivity
      across the common gardens, the relative differences among the cross types
      remained constant. Using clonal replicates in a common garden, we found
      ANPP(tree) to be a heritable plant trait (i.e., broad-sense heritability), such
      that plant genetic factors explained between 38% and 82% of the variation in
      ANPP(tree). Furthermore, analysis of the genetic composition among individual
      tree genotypes using restriction fragment length polymorphism molecular markers
      showed that genetically similar trees also exhibited similar ANPP(tree). These
      findings indicate strong genetic contributions to natural variation in ANPP with
      important ecological implications.

PMID- 19578031
TI  - Housing repossessions, evictions and common mental illness in the UK: results
      from a household panel study.
AB  - BACKGROUND: The numbers of housing repossessions and evictions in the UK are
      increasing. This study investigates whether repossessions and evictions increase
      the likelihood of common mental illness and examine patterns over time. METHODS:
      Data come from the core longitudinal panel of the British Household Panel Survey
      (N = 12,390) of adults living in private households. Multivariate fixed-effects
      regression models are used with weighted data. Common mental illness is measured
      by the 12-item General Health Questionnaire. RESULTS: Housing repossession is
      associated with an increased risk of common mental illness (adjusted odds ratio
      1.61, 95% confidence interval 1.10 to 2.36), whereas eviction from rented
      property shows no increased risk (0.97, 0.76 to 1.20). The pattern over time
      shows a clear increase in the years before repossession. CONCLUSIONS:
      Repossession of owned property, although a relatively rare event in the panel,
      significantly increases the risk of common mental illness immediately after the
      event. In contrast, eviction from rented property is a more common event but is
      not associated with an increased risk of common mental illness. This difference
      in association may be due to losing the security of owned housing and the often
      transitory nature of the rented housing population.

PMID- 19578032
TI  - Endovascular stent-grafts for the treatment of abdominal aortic aneurysms: NICE
      technology appraisal guidance.

PMID- 19578033
TI  - Ethnicity-related differences in left ventricular function, structure and
      geometry: a population study of UK Indian Asian and European white subjects.
AB  - OBJECTIVES: The authors studied healthy UK Indian Asian and European white
      subjects to assess whether functional, structural and geometrical properties of
      the left heart are intrinsically related to ethnicity. BACKGROUND: Quantitative
      assessment of cardiac function and structure is necessary to diagnose heart
      failure syndromes and is validated to refine risk prediction. A better
      understanding of the demographic factors that influence these variables is
      required. METHODS: 458 healthy subjects were recruited from the London Life
      Sciences Prospective Population (LOLIPOP) study. They underwent 2-D and tissue
      Doppler echocardiography for quantification of left ventricular (LV) function, LV
      volumes, left atrial volume index (LAVI), left ventricular mass index (LVMI) and
      relative wall thickness (RWT). RESULTS: Indian Asians had attenuated mitral
      annular systolic velocity (8.9 cm/s vs 9.5 cm/s, p<0.001), lower mitral annular
      early diastolic velocity (10.3 cm/s vs 11.0 cm/s, p<0.001) and higher E/Ea ratio
      (7.9 vs 7.0, p<0.001) compared to European white subjects. Although Indian Asians
      had significantly smaller left heart volumes and LVMI, they had a significantly
      higher RWT (0.37 vs 0.35, p<0.001). After adjustment for covariates, these
      ethnicity-related differences remained highly significant (p<0.001). CONCLUSION:
      Compared to European white people, Indian Asians had attenuated longitudinal LV
      function, higher LV filling pressure and demonstrated a greater degree of
      concentric remodelling independent of other demographic and clinical parameters.

PMID- 19578034
TI  - The unfolding clinical spectrum of POLG mutations.
AB  - BACKGROUND: Mutations in the DNA polymerase-gamma (POLG) gene are a major cause
      of clinically heterogeneous mitochondrial diseases, associated with mtDNA
      depletion and multiple deletions. OBJECTIVE: To determine the spectrum of POLG
      mutations in our Dutch patient cohort, to evaluate the pathogenicity of novel
      mutations, and to establish genotype-phenotype correlations. RESULTS: The authors
      identified 64 predominantly recessive mutations in 37 patients from a total of
      232 patients, consisting of 23 different mutations. The substitution p.A467T was
      most frequently observed (n = 23), but was as frequent in childhood cases as in
      adult cases. Five new pathogenic recessive mutations, p.Lys925ArgfsX42, p.R275X,
      p.G426S, p.A804T and p.R869Q were identified. The known dominant chronic
      progressive external ophthalmoplegia (CPEO) mutation p.R943H was for the first
      time associated with premature ovarian failure as well. In 19 patients the
      authors identified only a single recessive mutation, or a sequence variant with
      unclear clinical significance. The data substantiate earlier observations that in
      POLG patients a fatal status epilepticus and liver failure can be triggered by
      sodium valproate. It is therefore important to exclude POLG mutations before
      administering this treatment. CONCLUSION: The clinical features of the patient
      are the most important features to select putative POLG mutation carriers and not
      the presence of mtDNA deletions or OXPHOS (oxidative phosphorylation) activity.
      The authors conclude that POLG mutations are an important cause of heterogeneous
      mitochondrial pathology and that more accurate genotype-phenotype correlations
      allow a more rapid genetic diagnosis and improved prognosis for mutation
      carriers.

PMID- 19578035
TI  - Enhancer deletions of the SHOX gene as a frequent cause of short stature: the
      essential role of a 250 kb downstream regulatory domain.
AB  - BACKGROUND: Mutations and deletions of the homeobox transcription factor gene
      SHOX are known to cause short stature. The authors have analysed SHOX enhancer
      regions in a large cohort of short stature patients to study the importance of
      regulatory regions in developmentally relevant genes like SHOX. METHODS: The
      authors tested for the presence of copy number variations in the pseudoautosomal
      region of the sex chromosomes in 735 individuals with idiopathic short stature
      and compared the results to 58 cases with Leri-Weill syndrome and 100 normal
      height controls, using fluorescence in situ hybridisation (FISH), single
      nucleotide polymorphism (SNP), microsatellites, and multiplex ligand dependent
      probe amplification (MLPA) analysis. RESULTS: A total of 31/735 (4.2%)
      microdeletions were identified in the pseudoautosomal region in patients with
      idiopathic short stature; eight of these microdeletions (8/31; 26%) involved only
      enhancer sequences residing a considerable distance away from the gene. In 58
      Leri-Weill syndrome patients, a total of 29 microdeletions were identified;
      almost half of these (13/29; 45%) involve enhancer sequences and leave the SHOX
      gene intact. These deletions were absent in 100 control persons. CONCLUSION: The
      authors conclude that enhancer deletions in the SHOX gene region are a relatively
      frequent cause of growth failure in patients with idiopathic short stature and
      Leri-Weill syndrome. The data highlights the growing recognition that regulatory
      sequences are of crucial importance in the genome when diagnosing and
      understanding the aetiology of disease.

PMID- 19578036
TI  - Segregation of enlarged vestibular aqueducts in families with non-diagnostic
      SLC26A4 genotypes.
AB  - BACKGROUND: Hearing loss with enlarged vestibular aqueduct (EVA) can be inherited
      as an autosomal recessive trait caused by bi-allelic mutations of SLC26A4.
      However, many EVA patients have non-diagnostic SLC26A4 genotypes with only one or
      no detectable mutant alleles. METHODS AND RESULTS: In this study, the authors
      were unable to detect occult SLC26A4 mutations in EVA patients with non
      diagnostic genotypes by custom comparative genomic hybridisation (CGH) microarray
      analysis or by sequence analysis of conserved non-coding regions. The authors
      sought to compare the segregation of EVA among 71 families with two (M2), one
      (M1) or no (M0) detectable mutant alleles of SLC26A4. The segregation ratios of
      EVA in the M1 and M2 groups were similar, but the segregation ratio for M1 was
      significantly higher than in the M0 group. Haplotype analyses of SLC26A4-linked
      STR markers in M0 and M1 families revealed discordant segregation of EVA with
      these markers in eight of 24 M0 families. CONCLUSION: The results support the
      hypothesis of a second, undetected SLC26A4 mutation that accounts for EVA in the
      M1 patients, in contrast to non-genetic factors, complex inheritance, or
      aetiologic heterogeneity in the M0 group of patients. These results will be
      helpful for counselling EVA families with non-diagnostic SLC26A4 genotypes.

PMID- 19578037
TI  - Novel FOXG1 mutations associated with the congenital variant of Rett syndrome.
AB  - BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder representing
      one of the most common genetic causes of mental retardation in girls. The classic
      form is caused by MECP2 mutations. In two patients affected by the congenital
      variant of Rett we have recently identified mutations in the FOXG1 gene encoding
      a brain specific transcriptional repressor, essential for early development of
      the telencephalon. METHODS: 60 MECP2/CDKL5 mutation negative European Rett
      patients (classic and variants), 43 patients with encephalopathy with early onset
      seizures, and four atypical Rett patients were analysed for mutations in FOXG1.
      RESULTS AND CONCLUSIONS: Mutations have been identified in four patients,
      independently classified as congenital Rett variants from France, Spain and
      Latvia. Clinical data have been compared with the two previously reported
      patients with mutations in FOXG1. In all cases hypotonia, irresponsiveness and
      irritability were present in the neonatal period. At birth, head circumference
      was normal while a deceleration of growth was recognised soon afterwards, leading
      to severe microcephaly. Motor development was severely impaired and voluntary
      hand use was absent. In contrast with classic Rett, patients showed poor eye
      contact. Typical stereotypic hand movements with hand washing and hand mouthing
      activities were present continuously. Some patients showed abnormal movements of
      the tongue and jerky movements of the limbs. Brain magnetic resonance imaging
      showed corpus callosum hypoplasia in most cases, while epilepsy was a variable
      sign. Scoliosis was present and severe in the older patients. Neurovegetative
      symptoms typical of Rett were frequently present.

PMID- 19578038
TI  - Efficient stochastic simulation of reaction-diffusion processes via direct
      compilation.
AB  - We present the Stochastic Simulator Compiler (SSC), a tool for exact stochastic
      simulations of well-mixed and spatially heterogeneous systems. SSC is the first
      tool to allow a readable high-level description with spatially heterogeneous
      simulation algorithms and complex geometries; this permits large systems to be
      expressed concisely. Meanwhile, direct native-code compilation allows SSC to
      generate very fast simulations.

PMID- 19578039
TI  - Antimony: a modular model definition language.
AB  - MOTIVATION: Model exchange in systems and synthetic biology has been standardized
      for computers with the Systems Biology Markup Language (SBML) and CellML, but
      specialized software is needed for the generation of models in these formats.
      Text-based model definition languages allow researchers to create models simply,
      and then export them to a common exchange format. Modular languages allow
      researchers to create and combine complex models more easily. We saw a use for a
      modular text-based language, together with a translation library to allow other
      programs to read the models as well. SUMMARY: The Antimony language provides a
      way for a researcher to use simple text statements to create, import, and combine
      biological models, allowing complex models to be built from simpler models, and
      provides a special syntax for the creation of modular genetic networks. The
      libAntimony library allows other software packages to import these models and
      convert them either to SBML or their own internal format. AVAILABILITY: The
      Antimony language specification and the libAntimony library are available under a
      BSD license from http://antimony.sourceforge.net/.

PMID- 19578040
TI  - TreeTime: an extensible C++ software package for Bayesian phylogeny
      reconstruction with time-calibration.
AB  - MOTIVATION: For the estimation of phylogenetic trees from molecular data, it is
      worthwhile to take prior paleontologic knowledge into account, if available. To
      calibrate the branch lengths of the tree with times assigned to geo-historical
      events or fossils, it is necessary to select a relaxed molecular clock model to
      specify how mutation rates can change along the phylogeny. RESULTS: We present
      the software TreeTime for Bayesian phylogeny estimation. It can take prior
      information about the topology of the tree and about branching times into
      account. Several relaxed molecular clock models are implemented in TreeTime.
      TreeTime is written in C++ and designed to be efficient and extensible.
      AVAILABILITY: TreeTime is freely available from
      http://evol.bio.lmu.de/statgen/software/treetime under the terms of the GNU
      General Public Licence (GPL, version 3 or later).

PMID- 19578041
TI  - FBA-SimVis: interactive visualization of constraint-based metabolic models.
AB  - FBA-SimVis is a VANTED plug-in for the constraint-based analysis of metabolic
      models with special focus on the visual exploration of metabolic flux data
      resulting from model analysis. The program provides a user-friendly environment
      for model reconstruction, constraint-based model analysis, and interactive
      visualization of the simulation results. With the ability to quantitatively
      analyse metabolic fluxes in an interactive and visual manner, FBA-SimVis supports
      a comprehensive understanding of constraint-based metabolic flux models in both
      overview and detail. AVAILABILITY: Software with manual and tutorials are freely
      available at http://fbasimvis.ipk-gatersleben.de/

PMID- 19578042
TI  - Negation of the cancer-preventive actions of selenium by over-expression of
      protein kinase Cepsilon and selenoprotein thioredoxin reductase.
AB  - Selenium prevents cancer in some cases but fails to do so in others. Selenium's
      failure in this respect may be due to the development of resistance to its
      chemopreventive actions. Selenocompounds induce a variety of cancer-preventive
      actions in tumor cells, but these actions may be limited by the low
      concentrations of free selenocompounds able to reach cells from the plasma.
      Therefore, we have sought to identify the chemopreventive action requiring the
      lowest concentration of the redox-active form of selenium, methylseleninic acid
      (MSA). At submicromolar concentrations, MSA inhibited the malignant
      transformation of RWPE-1 prostate epithelial cells. In contrast, in already
      transformed prostate cancer cells, selenium in the micromolar range was required
      to inhibit cell growth and invasion and to induce apoptosis. The role of protein
      kinase C (PKC) in these cellular processes, especially the moderately selenium
      sensitive PKCepsilon, was demonstrated using PKC-specific inhibitors and small
      interfering RNA. PKCepsilon levels inversely correlated with cellular sensitivity
      to MSA. An over-expression of PKCepsilon minimized MSA-induced inhibition of RWPE
      1 cell transformation and induction of apoptosis. Thioredoxin reductase (TR), a
      selenoprotein, reversed the MSA-induced inactivation of PKC isoenzymes. High TR
      expression in advanced prostate cancer cells correlated with resistance to MSA.
      Furthermore, inhibition of TR by its specific inhibitor, auranofin, resulted in
      increased sensitivity of prostate cancer cells to MSA. Collectively, these
      results suggest that the cancer-preventive actions of selenium may be negated
      both by an over-expression of PKCepsilon, which is a redox-sensitive target for
      MSA, and by the selenoprotein TR, which reverses PKC sulfhydryl redox
      modification.

PMID- 19578043
TI  - (-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at
      Ser1046/1047 by p38 MAPK in colon cancer cells.
AB  - We previously reported that (-)-epigallocatechin gallate (EGCG) in green tea
      alters plasma membrane organization and causes internalization of epidermal
      growth factor receptor (EGFR), resulting in the suppression of colon cancer cell
      growth. In the present study, we investigated the detailed mechanism underlying
      EGCG-induced downregulation of EGFR in SW480 colon cancer cells. Prolonged
      exposure to EGCG caused EGFR degradation. However, EGCG required neither an
      ubiquitin ligase (c-Cbl) binding to EGFR nor a phosphorylation of EGFR at
      tyrosine residues, both of which are reportedly necessary for EGFR degradation
      induced by epidermal growth factor. In addition, EGCG induced phosphorylation of
      p38 mitogen-activated protein kinase (MAPK), a stress-inducible kinase believed
      to negatively regulate tumorigenesis, and the inhibition of p38 MAPK by SB203580,
      a specific p38 MAPK inhibitor, or the gene silencing using p38 MAPK-small
      interfering RNA (siRNA) suppressed the internalization and subsequent degradation
      of EGFR induced by EGCG. EGFR underwent a gel mobility shift upon treatment with
      EGCG and this was canceled by SB203580, indicating that EGCG causes EGFR
      phosphorylation via p38 MAPK. Moreover, EGCG caused phosphorylation of EGFR at
      Ser1046/1047, a site that is critical for its downregulation and this was also
      suppressed by SB203580 or siRNA of p38 MAPK. Taken together, our results strongly
      suggest that phosphorylation of EGFR at serine 1046/1047 via activation of p38
      MAPK plays a pivotal role in EGCG-induced downregulation of EGFR in colon cancer
      cells.

PMID- 19578044
TI  - Cisplatin overcomes Bcl-2-mediated resistance to apoptosis via preferential
      engagement of Bak: critical role of Noxa-mediated lipid peroxidation.
AB  - Increased expression of antiapoptotic Bcl-2 proteins confers therapeutic
      resistance in various cancer types. Targeting Bcl-2 proteins by small molecules
      or activating alternative pathways to bypass Bcl-2-mediated protection to promote
      apoptosis are two approaches to overcoming therapeutic resistance. Here, we show
      that cisplatin triggers a Bak-dependent pathway to induce apoptosis in Bcl-2
      overexpressing MCF-7 cells. p53-mediated induction of Noxa expression, generation
      of lipid peroxidation end products and induction of Noxa-Mcl-1 interaction are
      necessary for this pathway to function. Although Puma is also induced by
      cisplatin treatment, it is not required for apoptosis. Similarly, reactive oxygen
      species production by cisplatin did not have any effect on cisplatin-induced
      apoptosis in MCF-7 Bcl-2 cells. Furthermore, p53 promotes cisplatin-induced
      apoptosis by directly binding and counteracting Bcl-x(L) antiapoptotic function.
      In conclusion, our findings suggest a novel mode of action for cisplatin to
      overcome Bcl-2-mediated protection against apoptosis, which requires preferential
      activation of Bak and p53-mediated upregulation of Noxa protein levels and lipid
      peroxidation.

PMID- 19578045
TI  - Elastofibromatous changes in tissues from spinal biopsies. A degenerative process
      afflicting a small but important subset of patients operated for spinal canal
      compression: report of 18 cases.
AB  - Elastofibroma is a tumorlike lesion occurring usually in the subscapular region
      of elderly females. In this study, 18 cases of elastofibromatous tissue retrieved
      from the spinal canal were analyzed to elucidate its frequency and possible
      clinical associations. The patients included 8 men and 10 women with a mean age
      of 63.4 years (range, 40-84 years). The elastic nature of the material was
      confirmed by Weigert's elastic stain and immunohistochemically. Elastofibroma was
      diagnosed in 6 patients, and elastofibroma-like tissue was found in 11 samples.
      The finding of elastofibromatous tissue was associated with clinical diagnosis of
      juxtaarticular cysts (3 cases), thickening of ligamentum flavum (4 cases),
      extradural expansion (2 cases), metastatic involvement of the dorsal spine (3
      cases), and a vertebral fracture (1 case). Two cases were located above the
      transpedicular fixation. Elastofibromatous tissue may be found in approximately
      2.6% of all spinal biopsies and it may take part in compression of spinal cord
      and nerve roots.

PMID- 19578046
TI  - Comparison of subtypes of penile squamous cell carcinoma from high and low
      incidence geographical regions.
AB  - There is a worldwide geographical variation in the incidence of penile squamous
      cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while
      others (keratinizing variants) are not. The aims of this study were to compare
      the distribution of different histological subtypes of PSCC from regions of low
      (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and
      compare tumors with and without warty and/or basaloid morphology. The
      distribution of subtypes in the Paraguayan and the American series was: usual,
      49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9
      and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5
      and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC
      was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual
      warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and
      5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no
      geographical difference in the incidence of histological subtypes (p = 0.6501),
      mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical
      variation may be the result of staging variation at clinical presentation or of
      pathological diagnosis. The identification of similar histological subtypes in
      both series validates this classification approach for penile cancer. The
      tendency for typical SCC to mix with verrucous and papillary carcinomas and of
      the basaloid to preferentially mix with benign condyloma and condylomatous
      (warty) carcinomas would support the hypothesis of the existence of an
      etiologically different dual population of penile tumors.

PMID- 19578047
TI  - High-grade astrocytomas show increased Nestin and Wilms's tumor gene (WT1)
      protein expression.
AB  - Wilms's tumor gene (WT1) is overexpressed in a variety of hematologic
      malignancies and solid tumors. Recently, WT1 protein has been considered as a
      molecular target of cancer immunotherapy for several solid tumors and as a tool
      for monitoring minimal residual disease in leukemia patients. There are only few
      investigations on WT1 expression in central nervous system neoplasms, which
      suggest that the WT1 gene may play an important role in tumorigenesis of primary
      astrocytic tumors and that high-grade tumors express high levels of WT1 proteins.
      We examined 50 low-grade and high-grade gliomas using tissue microarray and
      immunohistochemical methods to identify WT1 protein, P53, Ki-67, GFAP, NFP, EGFR,
      nestin, and Neu-N expression. WT1 and nestin shared overlapping expression in all
      gliomas and were increased in high-grade examples, highlighting their potential
      use as diagnostic and prognostic tumor markers. Our results support the combined
      role of WT1 and nestin in glial tumorigenesis and progression.

PMID- 19578048
TI  - Skip lesion of DIN (DCIS) in the nipple in a case of breast cancer.
AB  - The authors present a case of breast cancer with a skip lesion of DIN 1 (ductal
      carcinoma in situ [DCIS] grade 1) in the nipple, leaving the base of the nipple
      free of disease. During the surgical procedure of nipple-sparing mastectomy (NSM)
      a frozen section evaluation of the base of the nipple and areola complex is often
      carried out to ascertain absence of any intraepithelial (in situ) or invasive
      neoplasms that could lead to nipple recurrences if left behind. This case
      illustrates a situation where a frozen section would have given a false-negative
      prediction of nipple involvement if the patient had been selected for NSM. This
      case illustrates the need to adhere to strict criteria for selecting patients
      eligible for NSM and to consider the use of additional preoperative and
      intraoperative measurements and methods to refine the selection of candidates for
      NSM and enhance the oncological safety of the procedure.

PMID- 19578049
TI  - Thyroid transcription factor-1 and "basal marker"--expressing small cell
      carcinoma of the breast.
AB  - Small cell carcinoma of the breast is a very rare entity that is histologically
      indistinguishable from small cell carcinomas of other organs. The presence of an
      in situ component is the most important feature that indicates the primary nature
      of the breast tumor. Thyroid transcription factor-1 (TTF-1) is a marker specific
      to lung and thyroid but is also expressed in small cell carcinoma of pulmonary
      and extrapulmonary origin. TTF-1 expression in breast small cell carcinoma has
      been reported only rarely. This reported case is unique because of the
      characteristic morphological features and immunohistochemical profile. The
      invasive tumor demonstrated neuroendocrine differentiation morphologically and
      immunohistochemically, expressed by TTF-1, EGFR, and basal-type cytokeratins. An
      unequivocal in situ component was identified intimately admixed with the invasive
      carcinoma. To the authors' knowledge, this is the first report of breast small
      cell carcinoma showing the expression of "basal markers."

PMID- 19578050
TI  - Pathologic and clinical features of Hodgkin lymphoma--like posttransplant
      lymphoproliferative disease.
AB  - Because of its rarity, pathologic and clinical features of Hodgkin lymphoma-like
      posttransplant lymphoproliferative disorder (HL-like PTLD) are not well
      understood, and it is unclear whether its biological behavior is more closely
      related to classical Hodgkin disease or to monomorphic B-cell PTLD. The authors
      compared 6 cases of HL-like PTLD with 5 cases of monomorphic B-cell PTLD for
      differences in histology, immunophenotype, and clinical behavior. Histologically,
      all cases of HL-like PTLD resembled classical HL with typical Reed-Sternberg (RS)
      cells and a cellular background mimicking mixed cellularity subtype. CD45 was
      absent on RS-like cells, but the expression pattern of B-cell-associated markers
      Oct-2 and BOB.1 resembled monomorphic B-cell PTLD. Whereas Epstein-Barr virus
      early RNA expression is normally restricted to RS cells of classical HL, it was
      expressed in both RS-like cells and background lymphocytes in HL-like PTLD.
      Although all patients diagnosed with monomorphic B-cell PTLD show no evidence of
      disease following treatment, half of the patients with HL-like PTLD relapsed or
      died, indicating a more aggressive clinical behavior. The findings suggest that
      HL-like PTLD represents a distinct clinicopathologic entity with an aggressive
      clinical course.

PMID- 19578051
TI  - Complementary value of the Ki-67 proliferation index to the oncotype DX
      recurrence score.
AB  - Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen
      receptor-positive breast cancer, which is expressed as the recurrence score (RS).
      Studies have shown that patients with a high-risk RS will most likely benefit
      from adjuvant chemotherapy, but there is no proven advantage for patients with a
      low-risk RS who still face an average recurrence risk of 7%. In this study, the
      relationship between the RS and the cell cycle-related antigen Ki-67 was assessed
      in 32 breast carcinomas and evaluated for a potential association. Comparison of
      the RS with tumor type, grade, and the Ki-67 proliferation index (PI) revealed an
      overall concordance. However, some tumors with a low RS revealed a surprisingly
      high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas
      that recur. Therefore, the authors propose a combined evaluation of the RS and Ki
      67 PI to identify tumors with high recurrence potential from the low-risk and
      intermediate-risk RS groups.

PMID- 19578052
TI  - CDX2 expression in yolk sac component of testicular germ cell tumors.
AB  - CDX2 has been detected in the majority of colorectal adenocarcinoma cases and may
      be useful in determining the sites of origin of tumors. In this study, the
      authors evaluated CDX2 expression in germ cell tumors (GCTs) by
      immunohistochemistry. Forty cases of testicular GCTs and 8 cases of metastatic
      GCTs were retrieved for study. In the 40 cases of testicular GCTs, 13 were pure
      seminomas and 27 mixed GCTs. Yolk sac tumor (YST) was identified by morphology
      and glypican 3 staining in 20 testicular mixed GCTs. Of these 20 cases, 8 cases
      showed 1+ positivity for CDX2. Other primitive components of GCTs were negative.
      For the 6 cases of metastatic mixed GCT with YST, 4 cases were positive, 2+ in 2
      cases and 1+ in 2 cases. The positivity of CDX2 in GCTs warrants including YST in
      the differential diagnosis of adenocarcinoma of unknown origin.

PMID- 19578053
TI  - Local wisdom and health promotion: barrier or catalyst?
AB  - The respectful, appropriate use of local wisdom (LW) in health promotion
      increases penetration and longevity of positive behavior change. Collaborations
      based on mutual respect, flexibility and trust between health program organizers,
      traditional and local practitioners, and the communities being served are the
      goal for public health physicians in our modern, globalized world. This meta
      analysis reviewed literature from the past 18 years drawn from a wide range of
      sources. This investigations proposes a grassroots, material shift toward
      regarding health promotion interventions as partnerships when planning,
      executing, and evaluating health promotion projects. This holistic approach would
      be based on the premise that LW is equal to expert opinion. This article endorses
      the integration of LW at every stage of the health promotion process concluding
      that it is through empowerment and involvement of local communities, their
      culture and specific environmental conditions that best-practice health promotion
      can be achieved.

PMID- 19578055
TI  - Rectourethral fistula stenting: a technique for better fistula visualization and
      efficient repair.
AB  - In this study, the authors present a technical tip for better and easier
      visualization of rectourethral fistula both during dissection and fistula
      closure. In this technique, a small-caliber ureteral catheter is used for
      catheterization of the fistulous tract under direct urethroscopic guidance. Five
      cases were treated using this technique. All cases had either brachytherapy as a
      monotherapy or combined brachytherapy and external beam radiotherapy. All cases
      had the fistula completely healed except for one failed case that had a 2-cm
      fistula.

PMID- 19578054
TI  - Implementation of a direct-from-recovery-room discharge pathway: a process
      improvement effort.
AB  - BACKGROUND: The authors describe a process improvement effort to achieve direct
      from-recovery-room discharge for elective laparoscopic cholecystectomy patients-
      without prior patient selection. METHODS: The authors developed and implemented a
      new pathway, and then measured the learning curve (ie, success rate over time for
      direct discharge) and compared patients achieving direct discharge with patients
      admitted after surgery. RESULTS: The learning curve between the first patient and
      steady-state performance was 56 patients. A total of 80% of patients achieved
      direct discharge. Directly discharged patients were younger (P<.001), had lower
      ASA physical status classifications (P<.005), and left the recovery room earlier
      in the day (P<.0001). However, elderly patients and those with high ASA scores
      frequently could be directly discharged from the recovery room. CONCLUSIONS:
      Through small team based rapid cycle process improvement, direct-from-recovery
      room discharge of laparoscopic cholecystectomy patients can be achieved in an
      unselected patient population with a short learning curve.

PMID- 19578056
TI  - Pacemaker-mediated tachycardia with varying cycle length: what is the mechanism?
AB  - As new algorithms are being developed to promote intrinsic atrioventricular
      conduction in preventing the deleterious effects of right ventricular pacing,
      more complex rhythm strips can be encountered. In our patient with a dual-chamber
      implantable cardioverter-defibrillator, such an algorithm resulted in a pacemaker
      mediated tachycardia with several changes in cycle length.

PMID- 19578057
TI  - Electrophysiology: it is time to simplify!

PMID- 19578058
TI  - Long-term mortality predictors in patients with chronic bifascicular block.
AB  - AIMS: To evaluate the long-term mortality rate and to determine independent
      mortality risk factors in patients with bifascicular block (BFB). Patients with
      BFB are known to have a higher mortality risk than the general population, not
      only related to progression to atrio-ventricular block but also due to the
      presence of malignant ventricular arrhythmias. Previous observational and
      epidemiological studies including a high proportion of patients with structural
      heart disease have shown an important cardiac mortality rate and may not reflect
      the real outcome of patients with BFB. METHODS AND RESULTS: From March 1998 until
      December 2006, we prospectively studied 259 consecutive BFB patients, 213 (82%)
      of whom presenting with syncope/pre-syncope, undergoing electrophysiological
      study. After a median follow-up of 4.5 years (P25:2.16-P75:6.41), 53 patients
      (20.1%) died, 19 (7%) of whom due to cardiac aetiology. Independent total
      mortality predictors were age [hazard ratio (HR) 1.04, 95% confidence interval
      (CI) 1.01-1.09], NYHA class>or=II (HR 2.17, 95% CI 1.05-4.5), atrial fibrillation
      (HR 2.96, 95% CI 1.1-7.92), and renal dysfunction (HR 4.26, 95% CI 2.04-9.01). An
      NYHA class of >or=II (HR 5.45, 95% CI 2.01-14.82) and renal failure (HR 3.82, 95%
      CI 1.21-12.06) were independent predictors of cardiac mortality. No independent
      predictors of arrhythmic death were found. CONCLUSION: Total mortality,
      especially of cardiac cause, is lower than previously described in BFB patients.
      Advanced NYHA class and renal failure are predictors of cardiac mortality.

PMID- 19578059
TI  - Fractionated extracellular potentials: indicators of the arrhythmogenic
      substrate?

PMID- 19578060
TI  - Discovery of protein-DNA interactions by penalized multivariate regression.
AB  - Discovering which regulatory proteins, especially transcription factors (TFs),
      are active under certain experimental conditions and identifying the
      corresponding binding motifs is essential for understanding the regulatory
      circuits that control cellular programs. The experimental methods used for this
      purpose are laborious. Computational methods have been proven extremely effective
      in identifying TF-binding motifs (TFBMs). In this article, we propose a novel
      computational method called MotifExpress for discovering active TFBMs. Unlike
      existing methods, which either use only DNA sequence information or integrate
      sequence information with a single-sample measurement of gene expression,
      MotifExpress integrates DNA sequence information with gene expression measured in
      multiple samples. By selecting TFBMs that are significantly associated with gene
      expression, we can identify active TFBMs under specific experimental conditions
      and thus provide clues for the construction of regulatory networks. Compared with
      existing methods, MotifExpress substantially reduces the number of spurious
      results. Statistically, MotifExpress uses a penalized multivariate regression
      approach with a composite absolute penalty, which is highly stable and can
      effectively find the globally optimal set of active motifs. We demonstrate the
      excellent performance of MotifExpress by applying it to synthetic data and real
      examples of Saccharomyces cerevisiae. MotifExpress is available at
      http://www.stat.illinois.edu/~pingma/MotifExpress.htm.

PMID- 19578061
TI  - In vitro characterization of a miR-122-sensitive double-helical switch element in
      the 5' region of hepatitis C virus RNA.
AB  - It has been proposed that the hepatitis C virus (HCV) internal ribosome entry
      site (IRES) resides within a locked conformation, owing to annealing of its
      immediate flanking sequences. In this study, structure probing using Escherichia
      coli dsRNA-specific RNase III and other classical tools showed that this region
      switches to an open conformation triggered by the liver-specific microRNA, miR
      122. This structural transition, observed in vitro, may be the mechanistic basis
      for the involvement of downstream IRES structural domain VI in translation, as
      well as providing a role of liver-specific miR-122 in HCV infection. In addition,
      the induced RNA switching at the 5' untranslated region could ultimately
      represent a new mechanism of action of micro-RNAs.

PMID- 19578062
TI  - Qri7/OSGEPL, the mitochondrial version of the universal Kae1/YgjD protein, is
      essential for mitochondrial genome maintenance.
AB  - Yeast Qri7 and human OSGEPL are members of the orthologous Kae1(OSGEP)/YgjD
      protein family, the last class of universally conserved proteins without assigned
      function. Phylogenetic analyses indicate that the eukaryotic Qri7(OSGEPL)
      proteins originated from bacterial YgjD proteins. We have recently shown that the
      archaeal Kae1 protein is a DNA-binding protein that exhibits apurinic
      endonuclease activity in vitro. We show here that the Qri7/OSGEPL proteins
      localize in mitochondria and are involved in mitochondrial genome maintenance in
      two model eukaryotic organisms, Saccharomyces cerevisiae and Caenorhabditis
      elegans. Furthermore, S. cerevisiae Qri7 complements the loss of the bacterial
      YgjD protein in Escherichia coli, suggesting that Qri7/OSGEPL and YgjD proteins
      have retained similar functions in modern organisms. We suggest to name members
      of the Kae1(OSGEP)/YgjD family UGMP, for Universal Genome Maintenance Proteins.

PMID- 19578063
TI  - Large, sequence-dependent effects on DNA conformation by minor groove binding
      compounds.
AB  - To determine what topological changes antiparasitic heterocyclic dications can
      have on kinetoplast DNA, we have constructed ligation ladders, with phased A5 and
      ATATA sequences in the same flanking sequence context, as models. Bending by the
      A5 tract is observed, as expected, while the ATATA sequence bends DNA very
      little. Complexes of these DNAs with three diamidines containing either furan,
      thiophene or selenophene groups flanked by phenylamidines were investigated along
      with netropsin. With the bent A5 ladder the compounds caused either a slight
      increase or decrease in the bending angle. Surprisingly, however, with ATATA all
      of the compounds caused significant bending, to values close to or even greater
      than the A5 bend angle. Results with a mixed cis sequence, which has one A5 and
      one ATATA, show that the compounds bend ATATA in the same direction as a
      reference A5 tract, that is, into the minor groove. These results are interpreted
      in terms of a groove structure for A5 which is largely pre-organized for a fit to
      the heterocyclic amidines. With ATATA the groove is intrinsically wider and must
      close to bind the compounds tightly. The conformational change at the binding
      site then leads to significant bending of the alternating DNA sequence.

PMID- 19578064
TI  - Crystal structure and assembly of the functional Nanoarchaeum equitans tRNA
      splicing endonuclease.
AB  - The RNA splicing and processing endonuclease from Nanoarchaeum equitans (NEQ)
      belongs to the recently identified (alphabeta)(2) family of splicing
      endonucleases that require two different subunits for splicing activity. N.
      equitans splicing endonuclease comprises the catalytic subunit (NEQ205) and the
      structural subunit (NEQ261). Here, we report the crystal structure of the
      functional NEQ enzyme at 2.1 A containing both subunits, as well as that of the
      NEQ261 subunit alone at 2.2 A. The functional enzyme resembles previously known
      alpha(2) and alpha(4) endonucleases but forms a heterotetramer: a dimer of two
      heterodimers of the catalytic subunit (NEQ205) and the structural subunit
      (NEQ261). Surprisingly, NEQ261 alone forms a homodimer, similar to the previously
      known homodimer of the catalytic subunit. The homodimers of isolated subunits are
      inhibitory to heterodimerization as illustrated by a covalently linked catalytic
      homodimer that had no RNA cleavage activity upon mixing with the structural
      subunit. Detailed structural comparison reveals a more favorable hetero- than
      homodimerization interface, thereby suggesting a possible regulation mechanism of
      enzyme assembly through available subunits. Finally, the uniquely flexible active
      site of the NEQ endonuclease provides a possible explanation for its broader
      substrate specificity.

PMID- 19578065
TI  - DNA melting by RNA polymerase at the T7A1 promoter precedes the rate-limiting
      step at 37 degrees C and results in the accumulation of an off-pathway
      intermediate.
AB  - The formation of a transcriptionally active complex by RNA polymerase involves a
      series of short-lived structural intermediates where protein conformational
      changes are coupled to DNA wrapping and melting. We have used time-resolved
      KMnO(4) and hydroxyl-radical X-ray footprinting to directly probe conformational
      signatures of these complexes at the T7A1 promoter. Here we demonstrate that DNA
      melting from m12 to m4 precedes the rate-limiting step in the pathway and takes
      place prior to the formation of full downstream contacts. In addition, on the
      wild-type promoter, we can detect the accumulation of a stable off-pathway
      intermediate that results from the absence of sequence-specific contacts with the
      melted non-consensus -10 region. Finally, the comparison of the results obtained
      at 37 degrees C with those at 20 degrees C reveals significant differences in the
      structure of the intermediates resulting in a different pathway for the formation
      of a transcriptionally active complex.

PMID- 19578066
TI  - The MmeI family: type II restriction-modification enzymes that employ single
      strand modification for host protection.
AB  - The type II restriction endonucleases form one of the largest families of
      biochemically-characterized proteins. These endonucleases typically share little
      sequence similarity, except among isoschizomers that recognize the same sequence.
      MmeI is an unusual type II restriction endonuclease that combines endonuclease
      and methyltransferase activities in a single polypeptide. MmeI cuts DNA 20 bases
      from its recognition sequence and modifies just one DNA strand for host
      protection. Using MmeI as query we have identified numerous putative genes highly
      similar to MmeI in database sequences. We have cloned and characterized 20 of
      these MmeI homologs. Each cuts DNA at the same distance as MmeI and each modifies
      a conserved adenine on only one DNA strand for host protection. However each
      enzyme recognizes a unique DNA sequence, suggesting these enzymes are undergoing
      rapid evolution of DNA specificity. The MmeI family thus provides a rich source
      of novel endonucleases while affording an opportunity to observe the evolution of
      DNA specificity. Because the MmeI family enzymes employ modification of only one
      DNA strand for host protection, unlike previously described type II systems, we
      propose that such single-strand modification systems be classified as a new
      subgroup, the type IIL enzymes, for Lone strand DNA modification.

PMID- 19578068
TI  - VEGF therapy: a timely retreat.

PMID- 19578067
TI  - Dissociation of FKBP12.6 from ryanodine receptor type 2 is regulated by cyclic
      ADP-ribose but not beta-adrenergic stimulation in mouse cardiomyocytes.
AB  - AIMS: Beta-adrenergic augmentation of Ca(2+) sparks and cardiac contractility has
      been functionally linked to phosphorylation-dependent dissociation of FK506
      binding protein 12.6 (FKBP12.6) regulatory proteins from ryanodine receptors
      subtype 2 (RYR2). We used FKBP12.6 null mice to test the extent to which the
      dissociation of FKBP12.6 affects Ca(2+) sparks and mediates the inotropic action
      of isoproterenol (ISO), and to investigate the underlying mechanisms of cyclic
      ADP-ribose (cADPR) regulation of Ca(2+) sparks. METHODS AND RESULTS: Ca(2+)
      sparks and contractility were measured in cardiomyocytes and papillary muscle
      segments from FKBP12.6 null mice, and western blot analysis was carried out on
      sarcoplasmic reticulum microsomes prepared from mouse heart. Exposure to ISO
      resulted in a three- and two-fold increase in Ca(2+) spark frequency in wild-type
      (WT) and FKBP12.6 knockout (KO) myocytes, respectively, and Ca(2+) spark kinetics
      were also significantly altered in both types of cells. The effects of ISO on
      Ca(2+) spark properties in KO cells were inhibited by pre-treatment with
      thapsigargin or phospholamban inhibitory antibody, 2D12. Moreover, twitch force
      magnitude and the rate of force development were not significantly different in
      papillary muscles from WT and KO mice. Unlike beta-adrenergic stimulation, cADPR
      stimulation increased Ca(2+) spark frequency (2.8-fold) and altered spark
      kinetics only in WT but not in KO mice. The effect of cADPR on spark properties
      was not entirely blocked by pre-treatment with thapsigargin or 2D12. In voltage
      clamped cells, cADPR increased the peak Ca(2+) of the spark without altering the
      decay time. We also noticed that basal Ca(2+) spark properties in KO mice were
      markedly altered compared with those in WT mice. CONCLUSION: Our data demonstrate
      that dissociation of FKBP12.6 from the RYR2 complex does not play a significant
      role in beta-adrenergic-stimulated Ca(2+) release in heart cells, whereas this
      mechanism does underlie the action of cADPR.

PMID- 19578069
TI  - A new transmyocardial degradable stent combined with growth factor, heparin, and
      stem cells in acute myocardial infarction.
AB  - AIMS: We developed a new method-transmyocardial drilling revascularization (TMDR)
      with absorbable stent incorporated with basic fibroblast growth factor (bFGF) and
      heparin. The present study tested the effect of this method with transplantation
      of bone marrow-derived stem cells (BMSCs) in acute myocardial infarction. METHODS
      AND RESULTS: Infarction was produced in mini-swine by ligating the left anterior
      descending (LAD) coronary artery. TMDR of 3.0 mm in diameter was made by
      mechanical drilling in the infarcted area. The animals that had LAD ligation were
      divided into six groups according to the procedures followed (n = 6 in each):
      control; T (TMDR); C (cell implantation); TS (TMDR+stent implantation); TC
      (TMDR+cell implantation); TSC (TMDR+stent implantation+cell implantation). Left
      ventricular (LV) function, myocardial perfusion, vascular density, and
      histological and morphological analyses were evaluated pre-operatively and at 30
      min and 6 weeks post-operatively. Six weeks after operation, the above indices
      were significantly better in the TSC group than in other groups (P < 0.001
      compared with the control group, and P < 0.05 or 0.01 compared with the TS and TC
      groups), although TS and TC also showed better results than the control group (P
      < 0.05). CONCLUSION: We have demonstrated in a pig model that an intramyocardial
      stent implanted with slow release of bFGF, heparin, and BMSC transplantation may
      significantly increase LV function, cardiac blood flow, and vascular density.
      Therefore, the present study may provide a new method for the surgical treatment
      of myocardial infarction.

PMID- 19578070
TI  - Maintenance of adrenergic vascular tone by MMP transactivation of the EGFR
      requires PI3K and mitochondrial ATP synthesis.
AB  - AIMS: G-protein-coupled receptors (GPCRs) modulate vascular tone, at least in
      part, via matrix metalloproteinase (MMP) transactivation of the epidermal growth
      factor receptor (EGFR). We previously have identified novel signalling pathways
      downstream of the EGFR suggestive of mitogen-activated protein kinase and
      mitochondrial redox control of vascular tone. In the present study, we examined
      whether MMP modulation of vascular tone involves phosphoinositide 3-kinase (PI3K)
      and mitochondrial ATP synthesis. METHODS AND RESULTS: To determine whether PI3K
      is required for the maintenance of adrenergic vascular tone, we first constricted
      rat small mesenteric arteries with phenylephrine (PE) and then perfused with PI3K
      inhibitors, LY294002 and wortmannin, both of which produced a dose-dependent
      vasodilatation. Next, to investigate whether MMPs modulate PI3K activity, we
      cultured rat aortic vascular smooth muscle cells (VSMCs) and stimulated them with
      GPCR agonists such as PE and angiotensin II. Inhibition of MMPs (by GM6001) or
      EGFR (by AG1478) or suppressing the expression of MMP-2 or MMP-7 or the EGFR by
      small interfering RNA blunted the PI3K phosphorylation of Akt induced by PE.
      Further, in VSMCs, PI3K inhibitors reduced the PE-induced increase in ATP
      synthesis and glucose transporter-4 translocation, an effect that was also
      observed with MMP and the EGFR inhibitors. Further, the PE-induced increase in
      ATP synthesis activated MMP-7 by mechanisms involving purinergic (P2X) receptors
      and calcium. CONCLUSION: These data suggest that the maintenance of adrenergic
      vascular tone by the MMP-EGFR pathway requires PI3K activation and ATP synthesis.
      Further, our data support the view that elevated levels of GPCR agonists
      exaggerate the MMP transactivation of EGFR response and contribute to enhanced
      vascular tone and development of cardiovascular disease such as hypertension.

PMID- 19578071
TI  - Bone marrow-derived cells do not repair endothelium in a mouse model of chronic
      endothelial cell dysfunction.
AB  - AIMS: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the
      circulation replace damaged vascular endothelium. We assessed the hypothesis that
      a BM transplant from healthy animals would restore normal arterial endothelium
      and prevent hypertension in young endothelial nitric oxide synthase-deficient
      (eNOS(-/-)) mice. METHODS AND RESULTS: Radiation or busulfan-induced BM ablation
      in eNOS(-/-) mice on day 6, day 14, or day 28 was followed by a BM transplant
      consisting of enhanced green fluorescent protein positive (EGFP(+)) cells from
      C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4
      months after BM transplant. Molecular assays of heart, kidney, and liver revealed
      low-level chimerism in all treatment groups, consistent with residual circulating
      EGFP(+) blood cells. When aorta, coronary, renal, hepatic, and splenic arteries
      in BM-transplanted eNOS(-/-) mice were examined by confocal microscopy, there
      were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any
      of the treatment groups. Likewise, telemetry did not detect any reduction in
      blood pressure. Thus, no differences were observed in our measurements using
      several different treatment protocols. CONCLUSION: We found no evidence for BM
      derived EPC renewal of endothelium in this eNOS-deficient mouse model of a
      chronic vascular disease or in wild-type mice during postnatal growth. Hence,
      renewal of chronic dysfunctional endothelium and endothelial homeostasis may be
      dependent on resident vascular progenitor cells.

PMID- 19578072
TI  - Cx43 phosphorylation and cardioprotection.

PMID- 19578074
TI  - Protein degradation systems in viral myocarditis leading to dilated
      cardiomyopathy.
AB  - The primary intracellular protein degradation systems, including the ubiquitin
      proteasome and the lysosome pathways, have been emerging as central regulators of
      viral infectivity, inflammation, and viral pathogenicity. Viral myocarditis is an
      inflammatory disease of the myocardium caused by virus infection in the heart.
      The disease progression of viral myocarditis occurs in three distinct stages:
      acute viral infection, immune cell infiltration, and cardiac remodelling. Growing
      evidence suggests a crucial role for host proteolytic machineries in the
      regulation of the pathogenesis and progression of viral myocarditis in all three
      stages. Cardiotropic viruses evolve different strategies to subvert host protein
      degradation systems to achieve successful viral replication. In addition, these
      proteolytic systems play important roles in the activation of innate and adaptive
      immune responses during viral infection. Recent evidence also suggests a key role
      for the ubiquitin-proteasome and lysosome systems as the primary effectors of
      protein quality control in the regulation of cardiac remodelling. This review
      summarizes the recent advances in understanding the direct interaction between
      cardiotropic viruses and host proteolytic systems, with an emphasis on
      coxsackievirus B3, one of the primary aetiological agents causing viral
      myocarditis, and highlights possible roles of the host degradation systems in the
      pathogenesis of viral myocarditis and its progression to dilated cardiomyopathy.

PMID- 19578075
TI  - Cardiorespiratory fitness and the metabolic syndrome in firefighters.
AB  - BACKGROUND: The leading cause of mortality in on-duty firefighters is sudden
      cardiac death. While the reason for this remains unclear, low cardiorespiratory
      fitness and the metabolic syndrome have been associated with increased risk of
      cardiovascular disease-related events. AIMS: To document the levels of
      cardiorespiratory fitness and the metabolic syndrome, as well as to determine if
      there is a relationship between these variables, in firefighters. METHODS:
      Maximal cardiorespiratory fitness was assessed using the Bruce treadmill protocol
      in 214 male firefighters from Colorado. As part of a comprehensive cardiovascular
      disease risk evaluation, each firefighter was also screened for the metabolic
      syndrome using the National Cholesterol Education Program/Adult Treatment Panel
      III (NCEP/ATP III) guidelines. RESULTS: At the time of their evaluation, 32
      firefighters (15%) met the NCEP/ATP III diagnostic criteria for the metabolic
      syndrome, and 54 firefighters (25%) failed to achieve a generally accepted
      minimum cardiorespiratory fitness level of 42.0 ml/kg/min. A significant inverse
      trend of increasing cardiorespiratory fitness with decreasing metabolic
      abnormalities was found (P < 0.001). CONCLUSIONS: Increased levels of
      cardiorespiratory fitness are associated with an improved metabolic profile in
      male firefighters. Comprehensive cardiovascular disease risk factor management
      and cardiorespiratory fitness improvement are essential for firefighter health
      and safety.

PMID- 19578073
TI  - Proteasome inhibitors and cardiac cell growth.
AB  - Activation of the ubiquitin-proteasome system has been described in different
      models of cardiac hypertrophy. Cardiac cell growth in response to pressure or
      volume overload, as well as physiological adaptive hypertrophy, is accompanied by
      an increase in protein ubiquitination, proteasome subunit expression, and
      proteasome activity. Importantly, an inhibition of proteasome activity prevents
      and reverses cardiac hypertrophy and remodelling in vivo. The focus of this
      review is to provide an update about the mechanisms by which proteasome
      inhibitors affect cardiac cell growth in adaptive and maladaptive models of
      cardiac hypertrophy. In the first part, we summarize how the proteasome affects
      both proteolysis and protein synthesis in a context of cardiac cell growth. In
      the second part, we show how proteasome inhibition can prevent and reverse
      cardiac hypertrophy and remodelling in response to different conditions of
      overload.

PMID- 19578076
TI  - Non-Hodgkin lymphoma and occupational radiation exposure assessed using local
      data.
AB  - BACKGROUND: Our previous investigation of occupational exposure to ionizing
      radiation using a Finnish job-exposure matrix (JEM) showed no association with
      non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia.
      AIMS: To determine whether occupational exposure to ionizing radiation assessed
      using an Australian JEM is associated with NHL. METHODS: We analysed 694 NHL
      cases, first diagnosed between 1 January 2000 and 31 August 2001 and 694 controls
      from south-eastern Australia, matched by age, sex and region of residence. A
      detailed occupational history was obtained using a lifetime calendar and a
      telephone interview. Exposure to radiation was assessed using the ionizing
      radiation component of an Australian JEM. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated from logistic regression models that included the
      matching variables as covariates. RESULTS: The OR for workers ever exposed to
      ionizing radiation was 0.86 (95% CI = 0.52-1.40). Dividing the subjects into
      tertiles of exposure also found ORs that were close to or below the null for each
      exposure group. CONCLUSIONS: The application of an Australian JEM did not provide
      evidence for an association between NHL and occupational exposure to ionizing
      radiation and is consistent with previous analyses.

PMID- 19578077
TI  - Noise-induced hearing loss in French police officers.
AB  - BACKGROUND: There is a lack of data about police officers' hearing thresholds and
      the risk of noise-induced hearing loss (NIHL) associated with this occupation. In
      France, 129,000 national police officers, 96,000 state police force members and
      16000 municipal police officers may be affected by occupational noise exposure.
      AIMS: To evaluate the association between police employment and NIHL. METHODS: We
      undertook a cross-sectional study using review of medical records. Audiometric
      and otological data and information on potential confounders were extracted from
      medical records. Global hearing loss and selective 4000 Hz hearing loss were
      analysed. RESULTS: Of total, 1692 subjects (887 policemen and 805 civil servants)
      participated in the study. After adjusting for potential cofounders, police
      officers were 1.4 times more likely to have a selective 4000 Hz hearing loss than
      civil servants (95% CI 1.1-1.9). This difference was greater between motorcycle
      police officers and civil servants (OR = 3; 95% CI 1.4-6.3). CONCLUSIONS: These
      data suggest that occupational noise exposure in police work, particularly in
      motorcycle police officers, may induce hearing loss. Noise sources need to be
      more accurately defined to confirm high-level noise exposures, to better define
      significant sources of noise and to identify effective solutions.

PMID- 19578078
TI  - Endothelium-dependent and -independent vasodilation is more attenuated in
      ischaemic than in non-ischaemic heart failure.
AB  - AIMS: Endothelial dysfunction in chronic heart failure (CHF) contributes to
      vasoconstriction. Underlying atherosclerosis may increase vascular abnormalities
      in ischaemic CHF. We aimed to compare flow-mediated dilation (FMD) and
      nitroglycerin-mediated dilation (NMD) of the brachial artery between patients
      with ischaemic and non-ischaemic CHF. METHODS AND RESULTS: A total of 57 patients
      with systolic CHF participated in the study (mean age 59 +/- 8 years, 81% male).
      Patients were in stable NYHA class II (40 patients, 70%) and III (17 patients,
      30%). Ischaemic aetiology of CHF was confirmed by coronary angiography in 34
      (60%) patients and ruled out in 23 (40%). Flow-mediated dilation and NMD of the
      brachial artery was assessed by high-resolution ultrasound. Endothelium-dependent
      vasodilation was markedly reduced in patients with ischaemic CHF compared with
      those with non-ischaemic aetiology of CHF-mean absolute change in artery diameter
      (Deltad) 0.09 +/- 0.07 mm in ischaemic group vs. 0.18 +/- 0.07 mm in non
      ischaemic (P < 0.0001). Nitroglycerin-mediated vasodilation was also
      significantly different-Deltad = 0.14 +/- 0.06 mm in ischaemic vs. 0.31 +/- 0.10
      mm in non-ischaemic CHF (P < 0.0001). CONCLUSION: Endothelium-dependent and 
      independent vascular response is more attenuated in ischaemic than in non
      ischaemic CHF.

PMID- 19578079
TI  - Contribution of efflux to antibiotic resistance in Campylobacter isolated from
      poultry in Senegal.

PMID- 19578080
TI  - In vitro activity of ceftaroline, ceftobiprole and cethromycin against clinical
      isolates of Streptococcus pneumoniae collected from across Canada between 2003
      and 2008.

PMID- 19578081
TI  - High fosfomycin concentrations in bone and peripheral soft tissue in diabetic
      patients presenting with bacterial foot infection.
AB  - OBJECTIVES: Appropriate antimicrobial therapy and surgical intervention may be
      required in diabetic patients presenting with severe bacterial foot infection.
      Methicillin-resistant Staphylococcus aureus (MRSA) agents such as fosfomycin are
      increasingly in demand because of recent concern regarding vancomycin and
      daptomycin efficacy and constant use. Intravenous fosfomycin is approved for the
      therapy of severe soft tissue infections and is highly active against methicillin
      susceptible S. aureus and MRSA. in the present study we investigated fosfomycin's
      ability to penetrate bone tissue in diabetic patients suffering from severe
      bacterial foot infection. PATIENTS AND METHODS: The well established
      microdialysis technique was utilized to determine fosfomycin concentrations in
      metatarsal bone in nine patients scheduled for partial bone resection due to
      bacterial foot infection and osteomyelitis. Plasma and unaffected subcutaneous
      adipose tissue served as reference compartments. RESULTS: After a single
      intravenous dose of approximately 100 mg of fosfomycin per kg of body weight, the
      mean C(max), T(max) and AUC(0-6) for bone were 96.4 mg/L, 3.9 h and 330.0 mg x
      h/L, respectively. The degree of tissue penetration as determined by the ratios
      of the AUC(0-6) for bone to plasma and for subcutaneous adipose tissue to plasma
      were 0.43 +/- 0.04 and 0.76 +/- 0.05, respectively. CONCLUSIONS: On the basis of
      relevant pharmacokinetic-pharmacodynamic indices, it seems that fosfomycin is an
      effective antibiotic for the treatment of deep-seated diabetic foot infections
      with osseous matrix involvement.

PMID- 19578082
TI  - Evolving perspectives on HIV-associated lipodystrophy syndrome: moving from
      lipodystrophy to non-infectious HIV co-morbidities.
AB  - This article will provide insight into the evolving perspectives on HIV-related
      lipodystrophy syndrome: recent changes in epidemiology, a shifting focus from
      individual component assessment towards a more comprehensive risk evaluation for
      organ dysfunction and disease, the impact of patient-related outcomes in heath
      related quality of life and the integration of this syndrome into a wider
      scenario of a premature ageing process in HIV-infected people will be discussed.
      The time has come to proceed beyond lipodystrophy studies based on blood
      concentrations of lipids and glucose and body fat evaluation. Surrogate markers
      of organ disease associated with lipodystrophy better identify patients
      vulnerable to non-infectious co-morbidities (NICMs) rather than statistical risk
      algorithms. In this evolving perspective NICMs take the place of lipodystrophy in
      the description of the clinical spectrum of HIV disease and allow integration of
      this syndrome into the wider scenario of a premature ageing process in HIV
      infected people. Management of NICMs needs to be considered as part of a multi
      disciplinary holistic approach that accommodates the increasing number of factors
      influencing non-infectious HIV-related outcomes.

PMID- 19578083
TI  - Identification of multidrug- and carbapenem-resistant Acinetobacter baumannii in
      Canada: results from CANWARD 2007.
AB  - OBJECTIVES: Multidrug-resistant (MDR) Acinetobacter baumannii is a growing
      concern in many countries. This report describes patient demographics,
      antimicrobial susceptibilities and molecular characteristics of A. baumannii
      cases identified through the Canadian Ward Surveillance Study (CANWARD). In
      addition, clinical cases involving MDR carbapenem-resistant A. baumannii are also
      detailed in this report. METHODS: From January to December 2007, 12 hospital
      centres across Canada submitted pathogens from clinics, emergency rooms,
      intensive care units and medical/surgical wards as part of the CANWARD study.
      MICs were determined using microbroth dilution (CLSI). PCR and sequence analysis
      identified OXA genes among carbapenem-resistant isolates. PFGE was used to
      determine genetic relatedness and compare representatives of the Midlands 2
      strain, OXA-23 clone 1 or 2, T strains and isolates collected from military
      sources. RESULTS: This study identified A. baumannii in 0.33% (n = 26) of
      infections. The majority of isolates remained susceptible to the antimicrobials
      tested, however, 7.7% (n = 2) displayed an MDR phenotype, including resistance to
      carbapenems. In one isolate bla(OXA-58) was found to be the likely cause of
      carbapenem resistance while the other isolate had an insertion sequence element
      upstream of its intrinsic bla(OXA-51). The clinical data of these two isolates
      suggest that one is travel-related while the source of the other remains unknown.
      CONCLUSIONS: A. baumannii infections from Canadian hospitals were relatively low.
      Carbapenem-resistant MDR A. baumannii were also rare and unrelated to previously
      observed isolates from military sources. Continued surveillance in Canada is
      suggested in order to determine if such organisms will become a problem.

PMID- 19578084
TI  - Imuunosuppressants, mortality, and risk of cancer.

PMID- 19578085
TI  - Cow's milk allergy in children.

PMID- 19578086
TI  - Lithium and chronic kidney disease.

PMID- 19578090
TI  - BMA meeting: Doctors urge government to lower age limit for cervical cancer
      screening.

PMID- 19578087
TI  - Overall and cancer related mortality among patients with ocular inflammation
      treated with immunosuppressive drugs: retrospective cohort study.
AB  - CONTEXT: Whether immunosuppressive treatment adversely affects survival is
      unclear. OBJECTIVE: To assess whether immunosuppressive drugs increase mortality.
      DESIGN: Retrospective cohort study evaluating overall and cancer mortality in
      relation to immunosuppressive drug exposure among patients with ocular
      inflammatory diseases. Demographic, clinical, and treatment data derived from
      medical records, and mortality results from United States National Death Index
      linkage. The cohort's mortality risk was compared with US vital statistics using
      standardised mortality ratios. Overall and cancer mortality in relation to use or
      non-use of immunosuppressive drugs within the cohort was studied with survival
      analysis. SETTING: Five tertiary ocular inflammation clinics. Patients 7957 US
      residents with non-infectious ocular inflammation, 2340 of whom received
      immunosuppressive drugs during follow up. Exposures Use of antimetabolites, T
      cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors. MAIN
      OUTCOME MEASURES: Overall mortality, cancer mortality. RESULTS: Over 66 802
      person years (17 316 after exposure to immunosuppressive drugs), 936 patients
      died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to
      immunosuppressive treatment, risks of death overall (standardised mortality ratio
      1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to
      1.29) were similar to those of the US population. Patients who used azathioprine,
      methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or
      dapsone had overall and cancer mortality similar to that of patients who never
      took immunosuppressive drugs. In patients who used cyclophosphamide, overall
      mortality was not increased and cancer mortality was non-significantly increased.
      Tumour necrosis factor inhibitors were associated with increased overall
      (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality
      (adjusted HR 3.83, 1.13 to 13.01). CONCLUSIONS: Most commonly used
      immunosuppressive drugs do not seem to increase overall or cancer mortality. Our
      results suggesting that tumour necrosis factor inhibitors might increase
      mortality are less robust than the other findings; additional evidence is needed.

PMID- 19578092
TI  - UK government predicts 100,000 new A/H1N1 flu cases a day by September.

PMID- 19578094
TI  - Evaluation of creatinine-based formulas in dosing adjustment of cancer drugs
      other than carboplatin.
AB  - BACKGROUND: Glomerular filtration rate (GFR) is often used to determine initial
      dosing of renally excreted cancer drugs. GFR can be calculated using the
      Cockcroft-Gault (CG) or the modified diet in renal diseases (MDRD) study
      formulas, both of which are based on serum creatinine levels. The MDRD formula is
      more accurate in noncancer patients, does not require patient weight, and is
      reported automatically by all laboratories in British Columbia, Canada. We
      previously showed that the CG and MDRD formulas have similar accuracy for
      carboplatin dosing in patients with gynecological malignancies. We now examine
      dosing of all renally excreted cancer drugs in the general cancer population.
      Since this setting does not include routine measurement of GFR, we report the
      concordance of estimates of GFR derived from the CG and MDRD formulas. METHODS:
      Patient data were collected retrospectively at the BC Cancer Agency. The primary
      outcome was the proportion of patients who would have received a different
      initial dose due to difference in the GFR. Each patient's dose was determined
      from dose adjustment tables stated in specific treatment protocols. The secondary
      outcome was concordance of the GFR derived from CG and MDRD, using the method of
      Bland and Altman. A difference of >30% was assumed to be clinically significant
      because this difference would usually lead to dose adjustment based on
      reclassification of renal function. RESULTS: A total of 313 patients were
      evaluated, with 40% male. The median age was 56 years, weight 67.5 kg, height 166
      cm, and serum creatinine 74 micromol/L (0.84 mg/dL). The median GFR derived from
      the CG and MDRD formulas were 86.8 mL/min (mean 91 mL/min, SD +/- 30 mL/min) and
      87.6 mL/min (mean 88 mL/min, SD +/- 26 mL/min), respectively. A total of 8.6%
      (27/313) of patients would have received a different dose due to difference in
      the GFR; of these, 67% (18/27) would have received a higher dose. A difference of
      >30% in GFR was found in 17.9% (56/313) of patients. CONCLUSIONS: There is good
      concordance of the GFR derived from the CG and MDRD formulas for most cancer
      patients, with less than 10% of patients expected to receive a different initial
      dose of chemotherapy. The MDRD formula may be a reasonable alternative to the CG
      formula for dosing of cancer drugs which are renally excreted or nephrotoxic.

PMID- 19578095
TI  - Downregulation of peroxisome proliferator-activated receptor alpha and its
      coactivators in liver and skeletal muscle mediates the metabolic adaptations
      during lactation in mice.
AB  - Previous studies have shown that genes involved in fatty acid uptake, fatty acid
      oxidation, and thermogenesis are downregulated in liver and skeletal muscle of
      rats during lactation. However, biochemical mechanisms underlying these important
      metabolic adaptations during lactation have not yet been elucidated. As all these
      genes are transcriptionally regulated by peroxisome proliferator-activated
      receptor alpha (Pparalpha), we hypothesized that their downregulation is mediated
      by a suppression of Pparalpha during lactation. In order to investigate this
      hypothesis, we performed an experiment with lactating and nonlactating Pparalpha
      knockout and corresponding wild-type mice. In wild-type mice, lactation led to a
      considerable downregulation of Pparalpha, Ppar coactivators Pgc1alpha and
      Pgc1beta, and Pparalpha target genes involved in fatty acid uptake, fatty acid
      oxidation, and thermogenesis in liver and skeletal muscle (P<0.05). Pparalpha
      knockout mice had generally a lower expression of all these Pparalpha target
      genes in liver and skeletal muscle. However, in those mice, lactation did not
      lower the expression of genes involved in fatty acid utilization and
      thermogenesis in liver and skeletal muscle. Expression levels of Pparalpha target
      genes in lactating wild-type mice were similar than in lactating or nonlactating
      Pparalpha knockout mice. In conclusion, the present findings suggest that
      downregulation of Pparalpha and its coactivators in tissues with high rates of
      fatty acid catabolism is responsible for the reduced utilization of fatty acids
      in liver and skeletal muscle and the reduced thermogenesis occurring in the
      lactating animal, which aim to conserve energy and metabolic substrates for milk
      production in the mammary gland.

PMID- 19578096
TI  - Cellular approaches to central nervous system remyelination stimulation: thyroid
      hormone to promote myelin repair via endogenous stem and precursor cells.
AB  - Brain and spinal cord repair is a very difficult task in view of the extremely
      limited repair capability of the mature central nervous system (CNS). Thus,
      cellular therapies are regarded as a new frontier for both acute and chronic
      neurological diseases characterized by neuron or oligodendroglia degeneration.
      Although cell replacement has been considered as the primary goal of such
      approaches, in recent years greater attention has been devoted to the possibility
      that new undifferentiated cells in damaged nervous tissue might also act in
      autocrine-paracrine fashion, regulating the micro-environment through the release
      of growth factor and cytokines, also regulating immune response and local
      inflammation. In this review, repair of demyelinating disease using endogenous
      cells will be discussed in view of the critical role played by thyroid hormones
      (THs) during developmental myelination, focusing on the following points: 1)
      endogenous stem and precursor cells during demyelinating diseases; 2) TH
      homeostasis in the CNS; 3) cellular and molecular mechanism regulated by TH
      during developmental myelination and 4) a working hypothesis to develop a
      rationale for the use of THs to improve remyelination through endogenous stem and
      precursor cells in the course of demyelinating diseases.

PMID- 19578097
TI  - Kidney function and future risk for adverse pregnancy outcomes: a population
      based study from HUNT II, Norway.
AB  - BACKGROUND: Current knowledge on prepregnancy reduced kidney function and the
      risk of adverse pregnancy outcomes mainly relies on small studies in selected
      populations. We aim to investigate whether reduced kidney function is associated
      with the risk of adverse pregnancy-related outcomes in the general population.
      METHODS: A population-based study linking all women attending the Second Health
      Study in Nord-Trondelag, Norway (1995-97) and subsequent pregnancies registered
      in the Medical Birth Registry. Multivariable random-effect logistic regression
      analysis was used to explore the association between renal function and study
      outcome. RESULTS: The mean eGFR among 3405 women was 107.6 +/- 19.4 ml/min/1.73
      m(2) at baseline; 18.8% and 0.1% had eGFR of 60-89 and <60, respectively. Over
      the next 11 years, they gave birth to 5655 singletons of whom 885 (17.7%) were
      complicated with preeclampsia, small for gestational age (SGA) or preterm birth.
      Women with eGFR 60-89 were not at increased risk for this combined outcome
      compared to women with eGFR > or =90, although women with eGFR 60-74 tended to
      have an increased risk. Neither was reduced kidney function a risk factor among
      women with microalbuminuria, but those with an eGFR of 60-89 plus hypertension
      had a significantly increased risk: odds ratios for preeclampsia, SGA or preterm
      birth were 2.58 (95% CI 1.40-4.75, P < 0.001) and 10.09 (95% CI 2.38-42.87, P <
      0.001) in hypertensive women with eGFR 75-89 and 60-74, respectively. Relative
      excess risk due to interaction between reduced kidney function and hypertension
      was 2.23 (95% CI 1.35-3.10, P < 0.001). Women with a reduced kidney function were
      not at increased risk for other pregnancy complications like caesarean section,
      maternal bleeding, dystocia, pre-labour rupture of membranes, Apgar score < or
      =7, stillbirth or congenital malformations. CONCLUSIONS: Women with eGFR 60-89
      ml/min/1.73 m(2) were not at increased risk for preeclampsia, SGA or preterm
      birth unless they were also hypertensive.

PMID- 19578098
TI  - Environmentally induced responses co-opted for reproductive altruism.
AB  - Reproductive altruism is an extreme form of altruism best typified by sterile
      castes in social insects and somatic cells in multicellular organisms. Although
      reproductive altruism is central to the evolution of multicellularity and
      eusociality, the mechanistic basis for the evolution of this behaviour is yet to
      be deciphered. Here, we report that the gene responsible for the permanent
      suppression of reproduction in the somatic cells of the multicellular green alga,
      Volvox carteri, evolved from a gene that in its unicellular relative,
      Chlamydomonas reinhardtii, is part of the general acclimation response to various
      environmental stress factors, which includes the temporary suppression of
      reproduction. Furthermore, we propose a model for the evolution of soma, in which
      by simulating the acclimation signal (i.e. a change in cellular redox status) in
      a developmental rather than environmental context, responses beneficial to a
      unicellular individual can be co-opted into an altruistic behaviour at the group
      level. The co-option of environmentally induced responses for reproductive
      altruism can contribute to the stability of this behaviour, as the loss of such
      responses would be costly for the individual. This hypothesis also predicts that
      temporally varying environments, which will select for more efficient acclimation
      responses, are likely to be more conducive to the evolution of reproductive
      altruism.

PMID- 19578100
TI  - Rituximab in systemic lupus erythematosus: A systematic review of off-label use
      in 188 cases.
AB  - The complexity of the therapeutic approach in systemic lupus erythematosus (SLE)
      is increased by the large number of patients who do not respond to the first-line
      therapies and by relapses after initial clinical remission. In these patients,
      second-line drugs are often prescribed according to individual clinical
      decisions. The emergence of biological therapies has increased the therapeutic
      armamentarium available in these complex situations, but their use is limited by
      the lack of licensing. Available data on the use of rituximab in SLE rely on a
      large number of case reports and some observational studies. We analyzed current
      evidence on the therapeutic use of rituximab in adult SLE patients by a
      systematic review of reports included in the PubMed database between 2002 and
      2007. A total of 188 SLE patients treated with rituximab were identified; 171
      (91%) patients showed a significant improvement in one or more of the systemic
      SLE manifestations. There were 103 patients with lupus nephritis, with an overall
      rate of therapeutic response of renal involvement of 91%. Adverse events were
      reported in 44 (23%) patients; the most frequent were infections (19%). Although
      it is not yet possible to make definite recommendations, the global analysis of
      all cases reported to date support the off-label use of rituximab in severe,
      refractory SLE cases, whereas its use as a first-line therapy or in patients with
      a predominantly mild form of the disease is not advised.

PMID- 19578099
TI  - Abnormal fluid homeostasis in apelin receptor knockout mice.
AB  - The apelinergic system, comprised of apelin and its G protein-coupled receptor
      (APJ; APLNR as given in MGI Database), is expressed within key regions of the
      central nervous system associated with arginine vasopressin (AVP) synthesis and
      release as well as in structures involved in the control of drinking behaviour,
      including the magnocellular neurones of the hypothalamus, circumventricular
      organs, and the pituitary gland. This localisation is indicative of a possible
      functional role in fluid homeostasis. We investigated a role for APJ in the
      regulation of fluid balance using mice deficient for the receptor. Male APJ wild
      type and knockout (APJ(-/-)) mice were housed in metabolic cages to allow
      determination of water intake and urine volume and osmolality. When provided with
      free access to water, APJ(-/-) mice drank significantly less than wild-types,
      while their urine volume and osmolality did not differ. Water deprivation for 24
      h significantly reduced urine volume and increased osmolality in wild-type but
      not in APJ(-/-) mice. Baseline plasma AVP concentration increased comparably in
      both wild-type and APJ(-/-) mice following dehydration; however, APJ(-/-) mice
      were unable to concentrate their urine to the same extent as wild-type mice in
      response to the V2 agonist desmopressin. Analysis of c-fos (Fos as given in MGI
      Database) mRNA expression in response to dehydration showed attenuation of
      expression within the subfornical organ, accentuated expression in the
      paraventricular nucleus, but no differences in expression in the supraoptic
      nucleus nor median pre-optic nucleus in APJ(-/-) mice compared with wild-type.
      These findings demonstrate a physiological role for APJ in mechanisms of water
      intake and fluid retention and suggest an anti-diuretic effect of apelin in vivo.

PMID- 19578101
TI  - Dyspnoea in a young woman with active systemic lupus erythematosus.
AB  - Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of
      systemic lupus erythematosus (SLE). We present the case of a 24-year-old
      Cambodian woman with SLE followed in the Brigham and Women's Hospital Lupus
      Center in Boston, Massachusetts. She presented with dyspnoea and chest pain and
      was found to have DAH that required a prolonged hospitalization that was
      complicated by recurrent DAH episodes and multiple infections. We discuss the
      diagnostic approach and management of patients with SLE-associated DAH as well as
      treatment options for refractory disease. Emerging therapies include
      plasmapheresis, the anti-CD20 monoclonal antibody rituximab and recombinant
      activated Factor VII therapy. In addition, we review the literature to date and
      compile what is known about the epidemiology, presenting features, diagnostic
      findings, management and outcomes in this condition. We found that DAH has been
      reported in 1.9% of patients with SLE. These patients were mostly female (88%)
      and young (mean age 30.2 years). Common presenting features included dyspnoea
      (94%), anaemia (97%) and new radiographic chest infiltrate (99%). Bronchoscopy,
      when performed, identified DAH in 90% of cases. Corticosteroids were the mainstay
      of care, and usage of cyclophosphamide varied by report. Despite recent advances
      in therapy, mortality has not improved substantially (48% overall survival versus
      53% survival in reports published since 1993).

PMID- 19578102
TI  - Increased T-lymphocyte apoptosis in lupus correlates with disease activity and
      may be responsible for reduced T-cell frequency: a cross-sectional and
      longitudinal study.
AB  - Apoptosis of lymphocytes is increased in patients with lupus. This may be
      pathogenic leading to increased load of autoantigens or may be a bystander effect
      of immune activation. A major unresolved issue is whether apoptosis is related to
      disease activity. Also its association with lymphocyte frequencies, anti
      nucleosomal antibodies and serum IL 10 levels needs to be explored further. The
      aims of this study are to measure T- and B-lymphocyte apoptosis in patients with
      lupus and look at the effect of disease activity in a cross-sectional and
      longitudinal design and to determine frequency of T and B cells, level of anti
      nucleosomal antibodies and serum IL 10 and assess their relationship with
      apoptosis. This study included 41 patients with SLE and 20 controls. A cutoff
      value of 4 in systemic lupus erythematosus disease activity index (SLEDAI) was
      used to separate active from inactive SLE. The frequency and degree of apoptosis
      of T and B lymphocyte were enumerated by flow cytometry using peripheral blood
      mononuclear cells (PBMCs) stained with CD3/CD19 and annexin V/PI. The data for
      T/B cell frequency are represented as % of these cells in the PBMC population,
      whereas percentage of apoptotic cells is out of total T or B cells. Serum anti
      nucleosomal antibodies and IL 10 were assayed using ELISA. A repeat assessment of
      these parameters was carried out in 11 active patients when they became inactive.
      We found higher T-lymphocyte apoptosis in patients with SLE versus controls (14.8
      +/- 9.2, 7.2 +/- 3.0; P < 0.05) and a lower frequency of T cells (72.7 +/- 12.6,
      79.9 +/- 5.8; P < 0.05). T-lymphocyte apoptosis was higher in patients with
      active disease compared with inactive (18.5 +/- 11.3, 11.6 +/- 5.4; P = 0.05).
      Further, T-lymphocyte apoptosis directly correlated with SLEDAI (r = 0.37, P <
      0.05) and inversely with T-cell frequency (r = -0.29, P < 0.05). Anti-nucleosomal
      antibodies correlated with SLEDAI but not apoptosis. On longitudinal follow-up, a
      decline in T-cell apoptosis was seen in patients with SLE, however this was not
      statistically significant. We confirmed a higher degree of apoptosis in T
      lymphocytes in patients with SLE and found a direct correlation of T-cell
      apoptosis with disease activity. Patients had reduced T-cell frequency, which
      inversely correlated with T-cell apoptosis and may suggest a cause-effect
      relationship.

PMID- 19578103
TI  - Serologic follow-up of children born to mothers with Ro/SSA autoantibodies.
AB  - Neonatal lupus erythematosus (NLE) develops in foetuses of mothers with Ro/SSA
      and La/SSB antibodies and may include foetal atrioventricular block and
      dermatologic manifestations. In this study, we investigated postnatal Ro and La
      IgG, IgA and IgM antibody levels up to 1 year of age in 32 children born to
      Ro/SSA positive mothers. Antibody levels were correlated with NLE manifestations,
      and the role of breast feeding in transfer of autoantibodies from mother to child
      was evaluated. Ro52, Ro60 and La IgG antibodies all transferred from the mothers
      to their foetus in utero and were present in the infant at birth as detected by
      enzyme-linked immunosorbent assay using recombinant antigens and a synthetic
      peptide. A significant decrease in Ro52, Ro60 and La IgG autoantibody levels of
      the infants was observed from birth to 4-5 weeks of age (P < 0.05, P < 0.05 and P
      < 0.01). Ro- and La-specific IgA and IgM antibodies were detected in the serum
      from a subset of mothers. However, Ro- and La-specific IgA and IgM antibody
      levels were low or non-detectable in children raised both with and without
      breastfeeding. Furthermore, NLE skin lesions developed independently of
      breastfeeding. Our findings support a role for placental materno-foetal transfer
      of IgG autoantibodies in the pathogenesis of NLE and indicate that refraining
      from breastfeeding does not protect from NLE skin involvement.

PMID- 19578105
TI  - The causes and clinical significance of fever in systemic lupus erythematosus: a
      retrospective study of 487 hospitalised patients.
AB  - The causes of fever in systemic lupus erythematosus (SLE) are complicated.
      Differential diagnosis of fever in SLE is crucial for optimal management of these
      patients. To better understand the causes and characteristics of fever in SLE,
      the medical records of 1949 consecutive patients hospitalised for SLE from
      January 2002 to May 2007 were reviewed. A total of 487 SLE-hospitalised patients
      with fever were identified and retrospectively analysed. Among them, 265 patients
      had fever from infection, 206 had fever related to SLE, 8 had fever caused by
      both SLE activity and infections, 4 had fever caused by malignancies and 4 had
      fever ascribed to miscellaneous causes. The most common sites of infection were
      the respiratory tract (62.6%), urinary tract (8.6%), skin and mucosa (8.3%). A
      prednisone dose of <or=100 mg/d was able to suppress SLE fever in 80.6% of the
      patients, usually within 1-5 days. Compared to patients with infection fever,
      those with SLE fever were more likely to have lower serum complement C3 and a
      higher SLE Disease Activity Index score. Infection fever was found to be
      associated with the use of azathioprine within the last six months. In
      conclusion, infection and disease activity are the most common causes of fever in
      SLE. Those patients for whom SLE fever could not be suppressed by a higher dose
      of steroids usually had severe lupus encephalopathy or hemophagocytic syndrome.

PMID- 19578104
TI  - Adipocytokines in systemic lupus erythematosus: relationship to inflammation,
      insulin resistance and coronary atherosclerosis.
AB  - We tested the hypothesis that concentrations of adipocytokines are altered in SLE
      and associated with coronary atherosclerosis, insulin resistance and
      inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were
      measured in 109 patients with SLE and 78 control subjects. Coronary calcification
      was measured using electron beam-computed tomography, and insulin resistance was
      defined by the homeostasis model assessment index. Concentrations of adiponectin
      (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs
      19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL,
      P < 0.001) were higher in patients with SLE than in controls. These differences
      remained significant after adjustment for age, race, sex and body mass index
      (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/-
      5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with
      SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin
      resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P =
      0.002), whereas adiponectin was negatively associated with the same factors (rho
      = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively).
      None of the adipocytokines were associated with coronary atherosclerosis in SLE.
      In conclusion, patients with SLE have increased concentrations of adiponectin,
      leptin and visfatin. Lower concentrations of adiponectin and higher
      concentrations of leptin are associated with insulin resistance, BMI and CRP in
      patients with SLE.

PMID- 19578106
TI  - Long-term follow-up after non-myeloablative transplant of bone and marrow in BXSB
      mice.
AB  - We present long-term outcomes of BXSB mice after non-myeloablative bone marrow
      transplants using major histocompatability complex (MHC)-matched cells. Groups
      differed in sources of donor lymphocytes or mesenchymal stromal cells (MSC).
      Unfractionated marrow cells from green fluorescent protein (GFP) transgenic (Tg)
      mice (BMT group) or from RAG1-/- B6 mice (RAG group) were injected intravenously
      (i.v.) into irradiated (550 cGy) hosts. As a source of mesenchymal cells, bone
      chips from GFP-Tg were injected intraperitoneally alone (MSC group) or along with
      i.v. bone marrow cells (BMT + MSC group). Controls were untreated mice (UnTx) or
      mice exposed to radiation only (Rad Cont). At 62 weeks post-transplant, surviving
      mice were harvested for histopathology, flow cytometry and real time polymerase
      chain reaction (RT-PCR). The mice from BMT + MSC group had the best outcomes for
      survival rates (71.4% vs. 43.8%), renal scores (2.9% vs. 28.8% glomerular
      sclerosis) and percent splenic monocytes (4.2 vs. 11.3%) compared with mice from
      Rad Cont. Improvement in RAG and BMT groups was less prominent but were
      comparable with one another. Although MSC alone were not sufficient to control
      the renal pathology, it limited the expansion of CD4(-)CD8(-) T cell populations
      without a change in Foxp3 expression. The results suggest the importance of the
      innate immune system in disease pathogenesis and a role for MSC in
      immunomodulation.

PMID- 19578108
TI  - Glomerular expression of toll-like receptor-9 in lupus nephritis but not in
      normal kidneys: implications for the amplification of the inflammatory response.
AB  - Toll-like receptors recognising self-derived nucleic acids may participate in the
      pathogenesis of autoimmune diseases. Following the description of an enhanced
      population of toll-like receptor-9 (TLR-9) expressing auto-antibody producing B
      lymphocytes in active lupus, we explored the expression of TLR-9 in the renal
      tissue of patients with lupus. TLR-9 expression was studied in the kidneys of 12
      lupus and 10 control samples from macroscopically unaffected areas of patients
      with renal adenocarcinoma by immunohistochemistry. A semiquantitative score was
      assigned separately for tubular, interstitial and glomerular expression. TLR-9
      was expressed in the renal tubules and interstitial tissue in both patients with
      lupus and controls. Six of 12 patients with lupus with proliferative or
      membranous nephritis - as compared to none of the controls - exhibited both
      tubulointerstitial and glomerular TLR-9 expression. Biopsies with glomerular TLR
      9 expression had a higher activity index (mean +/- SD, 6.3 +/- 3.5 in the
      presence of TLR-9 glomerular expression as compared to 1.3 +/- 1.8 in its
      absence, P = 0.015, t-test). This study documents for the first time the up
      regulation of TLR-9 within the glomerulus of patients with lupus nephritis.
      Activation of TLR-9 expressing glomerular cells by endogenous nucleic acids
      (nucleosomes) may amplify the inflammatory response.

PMID- 19578107
TI  - Time to neuropsychiatric damage occurrence in LUMINA (LXVI): a multi-ethnic lupus
      cohort.
AB  - The aims of this study were to examine the predictors of time to neuropsychiatric
      (NP) damage and its impact on mortality in 632 systemic lupus erythematosus
      African-American, Hispanic and Caucasian LUpus in MInorities: NAture versus
      Nurture (LUMINA) patients, age >or= 16 years and disease duration <or=5 years at
      baseline (T0). Time-to-NP damage and its impact on mortality were examined by Cox
      proportional hazards regressions. A total of 185 (29.3%) patients developed NP
      damage over a mean (SD) disease duration of 5.6 (3.7) years. After adjusting for
      NP manifestations present, older age [Hazard ratio (HR) = 1.02; 95% Confidence
      interval (CI) 1.00-1.04], Caucasian ethnicity (HR = 1.87; 95% CI, 1.22-2.87),
      disease activity over the disease course (HR = 1.16; 95% CI, 1.12-1.21), diabetes
      (HR = 3.47; 95% CI, 1.44-8.38) and abnormal illness-related behaviours (HR =
      1.05; 95% CI, 1.02-1.08) were associated with a shorter time-to-NP damage.
      Photosensitivity (HR = 0.65; 95% CI, 0.44-0.95), anaemia (HR = 0.56; 95% CI, 0.31
      0.98), Raynaud's phenomenon (HR = 0.49; 95% CI, 0.34-0.72), a medium dose of
      prednisone (HR = 0.56; 95% CI, 0.35-0.92) and hydroxychloroquine use (HR = 0.58;
      95% CI, 0.36-0.93) were associated with a longer time. NP damage did not
      contribute to mortality. Older age, Caucasian ethnicity, disease activity and
      abnormal illness-related behaviours are associated with a shorter time-to-NP
      damage; hydroxychloroquine and a medium dose of prednisone with a longer time.

PMID- 19578109
TI  - Third cranial nerve palsy or pseudo 3rd nerve palsy of myasthenia gravis? A
      challenging diagnosis in systemic lupus erythematosus.
AB  - Diplopia is frequently encountered in neurological practice and may occur as part
      of the clinical spectrum of 3rd cranial nerve palsy. Correct localization of the
      underlying problem is the first step in making an accurate diagnosis. Pathologies
      affecting the supranuclear structures, cranial nerves and nuclei, extraocular
      muscles and the neuromuscular junction may cause or simulate 3rd nerve palsy. We
      report a case of a patient with longstanding quiescent SLE who presented with
      sudden onset of diplopia and discuss possible aetiologies including ischemia,
      demyelination, neuromuscular conditions and medication-induced.

PMID- 19578110
TI  - Primary antiphospholipid syndrome with thrombotic thrombocytopenic purpura: a
      very unusual association.
AB  - This report considers the rare situation in which primary antiphospholipid
      syndrome (PAPS) is linked with thrombotic thrombocytopenic purpura (TTP). It
      describes the case of a young lady with PAPS, characterized by recurring cerebro
      vascular abnormalities and marked livedo reticularis, combined with circulating
      anticardiolipin and lupus anticoagulant antibodies. On follow-up, while on oral
      anticoagulation, she developed severe thrombocytopenia associated with hematuria,
      microangiophatic anaemia and neurological manifestations consistent with a
      diagnosis of TTP. The patient was treated with pulses of methylprednisolone and
      plasmapheresis with plasma exchange. The result was a favourable outcome. To our
      knowledge, this is the seventh report on this rare association in the English
      language literature of this field.

PMID- 19578111
TI  - Childhood stroke in a child with familial Mediterranean fever carrying several
      prothrombotic risk factors.
AB  - Familial Mediterranean fever (FMF) was recently associated with a hypercoagulable
      state. However, clinically overt thrombosis remains a rare event limited to
      patients with other predisposing factors. We herein present a child with FMF who
      experienced a stroke. An extensive thrombophilia work-up revealed multiple
      inherited and acquired risk factors. In areas with high prevalence of
      prothrombotic mutations and in children who are products of consanguineous
      marriages, early screening for concurrent thrombotic risk factors is warranted;
      as this may help design an optimal management plan and prevent unfavourable
      outcomes.

PMID- 19578112
TI  - Survival analysis and prognostic indicators of systemic lupus erythematosus in
      Pakistani patients.
AB  - To aim of this study is to analyse the survival rate and prognostic indicators of
      systemic lupus erythematosus (SLE) in Pakistani population. A total of 198
      patients with SLE diagnosed between 1992 and 2005 were reviewed retrospectively.
      Clinical features at presentation, subsequent evolving features, autoantibody
      profile, damage scores and mortality data were obtained. Prognostic factors for
      survival were studied by statistical analysis. Of 198 SLE patients studied, 174
      were women and 24 were men. The women to men ratio was 7.2:1. Mean age at
      presentation was 31 years (range 14-76). Mean duration of symptoms before
      diagnosis was 2.8 years. Mean duration of follow-up was 34.21 months (+/-33.69).
      Mean disease duration was 15.6 years. At diagnosis, arthritis, malar rash, oral
      ulcers and alopecia were the commonest features. During the follow-up, the
      prevalence of nephritis, arthritis, neurological and hematological disease
      increased significantly. About 76% (n = 151) of the patients had organ damage at
      the time of data analysis, and renal disease was the commonest cause. Univariate
      analysis revealed that renal disease (P = 0.000), seizures (P = 0.048), pleural
      involvement (P = 0.019), alopecia (P = 0.000) and discoid lesions (P = 0.005)
      were predictors for damage. Multivariate model, however, revealed that only renal
      disease was independent risk factor for damage (P = 0.002). During the study
      period, 47 patients (24%) died (five due to disease-related complications and
      rest as a result of infections). The 3-, 5-, 10-, 15- and 20-year survival rates
      of our cohort were 99, 80, 77, 75 and 75%, respectively. Cox regression analysis
      revealed that renal involvement (P = 0.002) and infections (P = 0.004) were
      independent risk factors for mortality. The survival of our Pakistani SLE
      patients was significantly lower compared to that of the Caucasian series
      reported in last decade. Nephritis not only contributes to organ damage but also
      acts a major determinant for survival. Infection remains the commonest cause of
      death. Renal involvement and infections are independent risk factors for
      mortality. Judicious use of immunosuppressive agents is necessary to improve the
      short-term survival of lupus patients.

PMID- 19578113
TI  - The case of SLE associated Sneddon-Wilkinson pustular disease successfully and
      safely treated with infliximab.

PMID- 19578114
TI  - Antilaminin-1 antibodies in cutaneous lupus erythematosus patients.

PMID- 19578115
TI  - Chemotherapy-induced subacute lupus erythematosus.

PMID- 19578116
TI  - Identification and characterization of ambroxol as an enzyme enhancement agent
      for Gaucher disease.
AB  - Gaucher disease (GD), the most prevalent lysosomal storage disease, is caused by
      a deficiency of glucocerebrosidase (GCase). The identification of small molecules
      acting as agents for enzyme enhancement therapy is an attractive approach for
      treating different forms of GD. A thermal denaturation assay utilizing wild type
      GCase was developed to screen a library of 1,040 Food and Drug Administration
      approved drugs. Ambroxol (ABX), a drug used to treat airway mucus hypersecretion
      and hyaline membrane disease in newborns, was identified and found to be a pH
      dependent, mixed-type inhibitor of GCase. Its inhibitory activity was maximal at
      neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH
      of lysosomes. The pH dependence of ABX to bind and stabilize the enzyme was
      confirmed by monitoring the rate of hydrogen/deuterium exchange at increasing
      guanidine hydrochloride concentrations. ABX treatment significantly increased
      N370S and F213I mutant GCase activity and protein levels in GD fibroblasts. These
      increases were primarily confined to the lysosome-enriched fraction of treated
      cells, a finding confirmed by confocal immunofluorescence microscopy.
      Additionally, enhancement of GCase activity and a reduction in glucosylceramide
      storage was verified in ABX-treated GD lymphoblasts (N370S/N370S).
      Hydrogen/deuterium exchange mass spectrometry revealed that upon binding of ABX,
      amino acid segments 243-249, 310-312, and 386-400 near the active site of GCase
      are stabilized. Consistent with its mixed-type inhibition of GCase, modeling
      studies indicated that ABX interacts with both active and non-active site
      residues. Thus, ABX has the biochemical characteristics of a safe and effective
      enzyme enhancement therapy agent for the treatment of patients with the most
      common GD genotypes.

PMID- 19578117
TI  - Molecular requirements for sorting of the chemokine interleukin-8/CXCL8 to
      endothelial Weibel-Palade bodies.
AB  - Sorting of proteins to Weibel-Palade bodies (WPB) of endothelial cells allows
      rapid regulated secretion of leukocyte-recruiting P-selectin and chemokines as
      well as procoagulant von Willebrand factor (VWF). Here we show by domain swap
      studies that the exposed aspartic acid in loop 2 (Ser(44)-Asp(45)-Gly(46)) of the
      CXC chemokine interleukin (IL)-8 is crucial for targeting to WPB. Loop 2 also
      governs sorting of chemokines to alpha-granules of platelets, but the fingerprint
      of the loop 2 of these chemokines differs from that of IL-8. On the other hand,
      loop 2 of IL-8 closely resembles a surface-exposed sequence of the VWF
      propeptide, the region of VWF that directs sorting of the protein to WPB. We
      conclude that loop 2 of IL-8 constitutes a critical signal for sorting to WPB and
      propose a general role for this loop in the sorting of chemokines to compartments
      of regulated secretion.

PMID- 19578118
TI  - Sac3 is an insulin-regulated phosphatidylinositol 3,5-bisphosphate phosphatase:
      gain in insulin responsiveness through Sac3 down-regulation in adipocytes.
AB  - Insulin-regulated stimulation of glucose entry and mobilization of fat/muscle
      specific glucose transporter GLUT4 onto the cell surface require the
      phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P(2)) pathway for optimal
      performance. The reduced insulin responsiveness observed under ablation of the
      PtdIns(3,5)P(2)-synthesizing PIKfyve and its associated activator ArPIKfyve in
      3T3L1 adipocytes suggests that dysfunction of the PtdIns(3,5)P(2)-specific
      phosphatase Sac3 may yield the opposite effect. Paradoxically, as uncovered
      recently, in addition to turnover Sac3 also supports PtdIns(3,5)P(2) biosynthesis
      by allowing optimal PIKfyve-ArPIKfyve association. These opposing inputs raise
      the key question as to whether reduced Sac3 protein levels and/or hydrolyzing
      activity will produce gain in insulin responsiveness. Here we report that small
      interfering RNA-mediated knockdown of endogenous Sac3 by approximately 60%, which
      resulted in a slight but significant elevation of PtdIns(3,5)P(2) in 3T3L1
      adipocytes, increased GLUT4 translocation and glucose entry in response to
      insulin. In contrast, ectopic expression of Sac3(WT), but not phosphatase
      deficient Sac3(D488A), reduced GLUT4 surface abundance in the presence of
      insulin. Endogenous Sac3 physically assembled with PIKfyve and ArPIKfyve in both
      membrane and soluble fractions of 3T3L1 adipocytes, but this remained insulin
      insensitive. Importantly, acute insulin markedly reduced the in vitro C8
      PtdIns(3,5)P(2) hydrolyzing activity of Sac3. The insulin-sensitive Sac3 pool
      likely controls a discrete PtdIns(3,5)P(2) subfraction as the high pressure
      liquid chromatography-measurable insulin-dependent elevation in total
      [(3)H]inositol-PtdIns(3,5)P(2) was minor. Together, our data identify Sac3 as an
      insulin-sensitive phosphatase whose down-regulation increases insulin
      responsiveness, thus implicating Sac3 as a novel drug target in insulin
      resistance.

PMID- 19578119
TI  - The direct binding of insulin-like growth factor-1 (IGF-1) to integrin
      alphavbeta3 is involved in IGF-1 signaling.
AB  - It has been proposed that ligand occupancy of integrin alphavbeta3 with
      extracellular matrix ligands (e.g. vitronectin) plays a critical role in insulin
      like growth factor-1 (IGF-1) signaling. We found that expression of alphavbeta3
      enhanced IGF-1-induced proliferation of Chinese hamster ovary cells in serum-free
      conditions (in the absence of vitronectin). We hypothesized that the direct
      integrin binding to IGF-1 may play a role in IGF-1 signaling. We demonstrated
      that alphavbeta3 specifically and directly bound to IGF-1 in cell adhesion,
      enzyme-linked immunosorbent assay-type binding, and surface plasmon resonance
      studies. We localized the amino acid residues of IGF-1 that are critical for
      integrin binding by docking simulation and mutagenesis. We found that mutating
      two Arg residues at positions 36 and 37 in the C-domain of IGF-1 to Glu (the
      R36E/R37E mutation) effectively reduced integrin binding. Interestingly, although
      the mutant still bound to IGF1R, it was defective in inducing IGF1R
      phosphorylation, AKT and ERK1/2 activation, and cell proliferation. Furthermore
      wild type IGF-1 mediated co-precipitation of alphavbeta3 and IGF1R, whereas the
      R36E/R37E mutant did not, suggesting that IGF-1 mediates the interaction between
      alphavbeta3 and IGF1R. These results suggest that the direct binding to IGF-1 to
      integrin alphavbeta3 plays a role in IGF-1 signaling through ternary complex
      formation (alphavbeta3-IGF-IGF1R), and integrin-IGF-1 interaction is a novel
      target for drug discovery.

PMID- 19578121
TI  - The epitope regions of H1-subtype influenza A, with application to vaccine
      efficacy.
AB  - The recent emergence of H1N1 (swine flu) illustrates the ability of the influenza
      virus to create antigens new to the human immune system, even within a given
      hemagglutinin and neuraminidase subtype. This new H1N1 strain is sufficiently
      distinct, for example, from the A/Brisbane/59/2007 (H1N1)-like virus strain of
      influenza in the 2008/09 Northern hemisphere vaccine that protection is not
      expected to be substantial. The human immune system responds primarily to the
      five epitope regions of the hemagglutinin protein. By determining the fraction of
      amino acids that differ between a vaccine strain and a viral challenge strain in
      the dominant epitope regions, a measure of antigenic distance that correlates
      with epidemiological studies of H3 influenza A vaccine efficacy in humans with
      R(2) = 0.81 is derived. This measure of antigenic distance is called p(epitope).
      The relation between vaccine efficacy and p(epitope) is given by E = 0.47 - 2.47
      x p(epitope). We here identify the epitope regions of H1 hemagglutinin, so that
      vaccine efficacy may be reliably estimated for H1N1 influenza A.

PMID- 19578122
TI  - Correction.

PMID- 19578120
TI  - Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice.
AB  - Kallikrein 4 (Klk4) is believed to play an essential role in enamel
      biomineralization, because defects in KLK4 cause hypomaturation amelogenesis
      imperfecta. We used gene targeting to generate a knockin mouse that replaces the
      Klk4 gene sequence, starting at the translation initiation site, with a lacZ
      reporter gene. Correct targeting of the transgene was confirmed by Southern blot
      and PCR analyses. Histochemical X-gal (5-bromo-4-chloro-3-indolyl-beta-d
      galactopyranoside) staining demonstrated expression of beta-galactosidase in
      maturation stage ameloblasts. No X-gal staining was observed in secretory stage
      ameloblasts or in odontoblasts. Retained enamel proteins were observed in the
      maturation stage enamel of the Klk4 null mouse, but not in the Klk4 heterozygous
      or wild-type mice. The enamel layer in the Klk4 null mouse was normal in
      thickness and contained decussating enamel rods but was rapidly abraded following
      weaning, despite the mice being maintained on soft chow. In function the enamel
      readily fractured within the initial rod and interrod enamel above the parallel
      enamel covering the dentino-enamel junction. Despite the lack of Klk4 and the
      retention of enamel proteins, significant levels of crystal maturation occurred
      (although delayed), and the enamel achieved a mineral density in some places
      greater than that detected in bone and dentin. An important finding was that
      individual enamel crystallites of erupted teeth failed to grow together,
      interlock, and function as a unit. Instead, individual crystallites seemed to
      spill out of the enamel when fractured. These results demonstrate that Klk4 is
      essential for the removal of enamel proteins and the proper maturation of enamel
      crystals.

PMID- 19578123
TI  - Rare pathogenic microdeletions and tandem duplications are microhomology-mediated
      and stimulated by local genomic architecture.
AB  - Genomic copy number variation (CNV) plays a major role in various human diseases
      as well as in normal phenotypic variability. For some recurrent disease-causing
      CNVs that convey genomic disorders, the causative mechanism is meiotic, non
      allelic, homologous recombination between breakpoint regions exhibiting extensive
      sequence homology (e.g. low-copy repeats). For the majority of recently
      identified rare pathogenic CNVs, however, the mechanism is unknown. Recently, a
      model for CNV formation implicated mitotic replication-based mechanisms, such as
      (alternative) non-homologous end joining and fork stalling and template
      switching, in the etiology of human pathogenic CNVs. The extent to which such
      mitotic mechanisms contribute to rare pathogenic CNVs remains to be determined.
      In addition, it is unexplored whether genomic architectural features such as
      repetitive elements or sequence motifs associated with DNA breakage stimulate the
      formation of rare pathogenic CNVs. To this end, we have sequenced breakpoint
      junctions of 30 rare pathogenic microdeletions and eight tandem duplications,
      representing the largest series of such CNVs examined to date in this much
      detail. Our results demonstrate the presence of (micro)homology ranging from 2 to
      over 75 bp, in 79% of the breakpoint junctions. This indicates that microhomology
      mediated repair mechanisms, including the recently reported fork stalling and
      template switching and/or microhomology-mediated break-induced replication,
      prevail in rare pathogenic CNVs. In addition, we found that the vast majority of
      all breakpoints (81%) were associated with at least one of the genomic
      architectural features evaluated. Moreover, 75% of tandem duplication breakpoints
      were associated with the presence of one of two novel sequence motifs. These data
      suggest that rare pathogenic microdeletions and tandem duplications do not occur
      at random genome sequences, but are stimulated and potentially catalyzed by
      various genomic architectural features.

PMID- 19578124
TI  - The monogenic primary dystonias.
AB  - Presently, 17 distinct monogenic primary dystonias referred to as dystonias 1- 4,
      5a,b, 6-8, 10-13 and 15-18 (loci DYT 1-4, 5a,b, 6-8, 10-13, 15-18) have been
      recognized. Twelve forms are inherited as autosomal dominant, four as autosomal
      recessive and one as an X-linked recessive trait. Three additional autosomal
      dominant forms (DYT9, DYT19 and DYT20) might exist based on linkage mapping to
      regions apparently different from, yet in close proximity to or overlapping with
      the known loci DYT18, DYT10 and DYT8. Clinically, this group of movement
      disorders includes pure dystonias and dystonia plus syndromes. In addition,
      dyskinesias (paroxysmal dystonias), although phenotypically distinct from
      classical dystonias, are discussed within this group. In pure dystonias, dystonia
      is occasionally accompanied by tremor. In dystonia plus syndromes, dystonia as
      the prominent sign concurs with other movement abnormalities such as myoclonus
      and parkinsonism. In the dyskinesias, dystonia occurs as a paroxysmal sign in
      association with other movement anomalies and sometimes seizures. While gross
      neuropathological changes are absent in most primary dystonias, including the
      paroxysmal forms, striking morphological alterations are found in some, such as
      in the X-linked dystonia-parkinsonism syndrome (DYT3). Neuropathological findings
      at the microscopic level have also been reported in several cases of dystonia 1
      and 5, both of which were previously thought to be morphologically normal. One
      locus, DYT14 had been erroneously assigned, by linkage mapping, in a family with
      dystonia 5. There are two forms of dystonia 5, one autosomal dominant and one
      autosomal recessive. These forms are designated here as dystonia 5a and dystonia
      5b (DYT5a, DYT5b), respectively. The disease gene has been identified in 10
      primary dystonias, seven autosomal dominant (TOR1A/DYT1, GCH1/DYT5a, THAP1/DYT6,
      PNKD1/MR-1/DYT8, SGCE/DYT11, ATP1A3/DYT12 and SLC2A1/DYT18), two autosomal
      recessive (TH/DYT5b and PRKRA/DYT16) and one X-chromosomal recessive (TAF1/DYT3).
      This article summarizes all known aspects on each of the monogenic primary
      dystonias, including phenotype, neuropathology, imaging, inheritance, mapping,
      molecular genetics, molecular pathology, animal models and treatment. Suggestions
      for the diagnostic procedure in primary dystonias are given. Although much is now
      known about the molecular basis of primary dystonias, treatment of patients is
      still mainly symptomatic. The only exceptions are dystonias 5a and 5b with their
      excellent long-term response to L-dopa substitution.

PMID- 19578125
TI  - Two-dimensional strain as a marker of subclinical anterior ischaemia in anomaly
      of left coronary artery arising from pulmonary artery.
AB  - A 13-year-old boy was admitted to our department after an out-of-hospital cardiac
      arrest during physical exertion. Transitory ST-segment elevation in the anterior
      chest leads was noted after defibrillation. At 48 h, initial evaluation was
      performed. Twelve-lead EKG and telemetry were normal. Transthoracic
      echocardiography showed normal left ventricle (LV) size and global function.
      Segmental two-dimensional (2D) longitudinal strain of the anterior wall was
      significantly decreased when compared with the other segments, and was associated
      with post-systolic shortening. Coronary angiography and 64-slice computed
      tomography revealed an anomalous origin of the left coronary artery from the
      pulmonary artery (ALCAPA). ALCAPA is a rare congenital malformation. The usual
      clinical course is a severe left-sided heart failure and mitral valve
      insufficiency presenting during the first months of life. In some cases,
      collateral blood supply from the right coronary artery is sufficient and symptoms
      may be subtle or even absent. However, ventricular arrhythmias or sudden cardiac
      death during exercise may be the first clinical presentation in patients with
      ALCAPA. Indirect evidence suggests that myocardial ischaemia is the underlying
      aetiology of cardiac ventricular ischaemia in patients with ALCAPA. Post-systolic
      shortening and altered longitudinal strain have recently been described as
      potential useful markers of ischaemic dysfunction in patients with ischaemic
      heart disease. In this case report, we demonstrate the usefulness of 2D strain as
      a non-invasive tool to assess subclinical myocardial ischaemia in patients with
      an ALCAPA. This provides further supportive evidence for the role of cardiac
      ischaemia in aetiology of ventricular arrhythmia in this rare condition.

PMID- 19578126
TI  - Sympathetic-mediated hypertension of awake juvenile rats submitted to chronic
      intermittent hypoxia is not linked to baroreflex dysfunction.
AB  - In the present study, we evaluated the mechanisms underpinning the hypertension
      observed in freely moving juvenile rats submitted to chronic intermittent hypoxia
      (CIH). Male juvenile Wistar rats (20-21 days old) were submitted to CIH (6% O(2)
      for 40 s every 9 min, 8 h day(1)) for 10 days while control rats were maintained
      in normoxia. Prior to CIH, baseline systolic arterial pressure (SAP), measured
      indirectly, was similar between groups (86 +/- 1 versus 87 +/- 1 mmHg). After
      exposure to CIH, SAP recorded directly was higher in the CIH (n = 28) than in the
      control group (n = 29; 131 +/- 3 versus 115 +/- 2 mmHg, P < 0.05). This higher
      SAP of CIH rats presented an augmented power of oscillatory components at low
      (10.05 +/- 0.91 versus 5.02 +/- 0.63 mmHg(2), P < 0.05) and high (respiratory
      related) frequencies (12.42 +/- 2.46 versus 3.28 +/- 0.61 mmHg(2), P < 0.05) in
      comparison with control animals. In addition, rats exposed to CIH also exhibited
      an increased cardiac baroreflex gain (3.11 +/- 0.08 versus 2.1 +/- 0.10 beats
      min(1) mmHg(1), P < 0.0001), associated with a shift to the right of the
      operating point, in comparison with control rats. Administration of hexamethonium
      (ganglionic blocker, i.v.), injected after losartan (angiotensin II type 1
      receptor antagonist) and [beta-mercapto-beta,beta-cyclopenta
      methylenepropionyl(1), O-Me-Tyr(2), Arg(8)]-vasopressin (vasopressin type 1a
      receptor antagonist), produced a larger depressor response in the CIH (n = 8)
      than in the control group (n = 9; 49 +/- 2 versus 39 +/- 2 mmHg, P < 0.05).
      Fifteen days after the cessation of exposure to CIH, the mean arterial pressure
      of CIH rats returned to normal levels. The data indicate that the sympathetic
      mediated hypertension observed in conscious juvenile rats exposed to CIH is not
      secondary to a reduction in cardiac baroreflex gain and exhibits a higher
      respiratory modulation, indicating that an enhanced respiratory-sympathetic
      coupling seems to be the major factor contributing to hypertension in rats
      exposed to CIH.

PMID- 19578127
TI  - Maternal anaemia and preterm birth: a prospective cohort study.
AB  - BACKGROUND: The role of maternal anaemia in preterm birth remains poorly defined,
      and the association between anaemia and preterm birth clinical subtypes remain
      unclear. We examined if maternal anaemia exposure both within and across
      trimesters during gestation is associated with preterm birth. METHODS: This was a
      secondary analysis of data from a population-based prospective cohort study in 13
      counties of East China (1993-96). All singleton live births delivered at 20-44
      weeks to women with at least one haemoglobin measure during pregnancy were
      included (n = 160 700). Risk of preterm birth (<37 weeks) was examined by
      clinical subtypes, namely, preterm premature rupture of membranes (PROM),
      spontaneous preterm labour and medically indicated preterm birth. Haemoglobin
      changes across trimesters were assessed as proxy of haemo-dilution and haemo
      concentration. Multivariable Cox proportional hazards regression models were
      fitted. RESULTS: Preterm birth rates of preterm birth were 4.1% for anaemic and
      5% for non-anaemic women (P < 0.05). Compared with haemoglobin of 11 g/dl
      (reference), values <or=5 g/dl in the first trimester were associated with
      increased risk for preterm PROM [hazard ratio (HR) 3.3, 95% confidence interval
      (CI) 1.4-7.7], whereas low haemoglobin in the third trimester was associated with
      reduced risk of spontaneous preterm labour. Haemodilution was associated with
      reduced risk for preterm birth. CONCLUSIONS: Anaemia in early pregnancy was found
      to be associated with increased risk for preterm PROM, whereas exposure in late
      pregnancy was associated with reduced risk for spontaneous preterm labour.

PMID- 19578128
TI  - Evaluation of a rapid immunochromatography strip test for detection of astrovirus
      in stool specimens.

PMID- 19578129
TI  - Neurofibromatosis type 1 with overlap Turner syndrome and Klinefelter syndrome.
AB  - Turner's syndrome is a sex chromosome disorder. Klinefelter's syndrome is one of
      the most severe genetic diseases. Neurofibromatosis is an autosomal dominant
      disorder characterized by cafe-au-lait spots and fibromatous tumors of the skin.
      In this article, we report the overlap of neurofibromatosis-1 with Turner and
      Klinefelter syndromes. Thus, these disorders might overlap within the same
      patient. Due to these cases, we suggest that each patient with Turner-like
      symptoms or Klinefelter's-like syndrome, be carefully examined for cafe au lait
      macules before the initiation of hormone replacement treatment.

PMID- 19578130
TI  - APOB gene signal peptide deletion polymorphism is not associated with infertility
      in Indian men.
AB  - Apolipoprotein B (APOB) plays a key role in lipoprotein metabolism and plasma
      lipid transport. It has been shown that about two-thirds of male mice
      heterozygous for ApoB were infertile. Moreover, a 3-codon deletion polymorphism
      (rs11279109) in the signal peptide region of the APOB gene has been shown to be a
      risk factor for infertility in Slovenian men, but its association with
      infertility in Indian men has not been evaluated to date. Hence, in the present
      study, we have genotyped this polymorphism in 545 Indian men, including 294
      infertile and 251 fertile men. Our results show that the distribution of this
      deletion polymorphism was consistent with the Hardy-Weinberg equilibrium in both
      infertile and fertile men. No statistically significant difference was observed
      in the distribution of the APOB signal peptide deletion polymorphism between
      infertile and fertile men (chi(2) = 0.156, P = .925 for genotypes; chi(2) =
      0.015, P = .903 for alleles). Moreover, no significant difference was observed
      when infertile and fertile men were categorized on the basis of presence (D/D and
      D/W genotypes) or absence (W/W genotypes) of deletion (odds ratio, 0.955; 95%
      confidence interval, 0.644-01.418; P = .820). Our study concludes that the APOB
      gene deletion polymorphism is not a risk factor for the development of
      infertility in Indian men.

PMID- 19578131
TI  - Viability tests, active caspase-3 and -7, and chromatin structure in ram sperm
      selected using the swim-up procedure.
AB  - Swim-up (SU) is a technique that permits the obtaining of motile sperm. Based on
      the sperm motility of neat ejaculates, we analyzed functional parameters,
      cytoplasmic esterases, and mitochondrial dehydrogenases of ram sperm using
      calcein acetomethylester and resazurin, respectively. Active caspase-3 and -7 and
      chromatin structure were evaluated in ram sperm before and after the SU process.
      There were no changes in any of the viability parameters after SU in neat semen
      samples with less or more than 25% motility. The percentage of active caspase-3
      and -7 decreased after SU (68.8 +/- 4.6 vs 54.2 +/- 6.0), whereas a small but
      significant increase of chromatin structural abnormalities was observed (DNA
      fragmentation index [DFI], 287.3 +/- 3.1 vs 297.2 +/- 2.4). For the first time,
      the location of active caspase-3 and -7 was described for ram sperm. Notably, we
      found active caspases in the implantation fossa region. The presence of active
      caspases in neat ejaculates and the diminished presence of active caspases in SU
      processed ejaculates suggest a role for caspases in motility and possibly in male
      fertility. The results of this study indicate that the evaluation of more than
      one cell-function marker is necessary to appropriately evaluate sperm quality.
      Furthermore, in semen samples with low motility, a lower percentage of sperm with
      active caspases is obtained after SU, although these sperm present increased
      values of DFI.

PMID- 19578132
TI  - Fifty-two-week treatment with diet and exercise plus transdermal testosterone
      reverses the metabolic syndrome and improves glycemic control in men with newly
      diagnosed type 2 diabetes and subnormal plasma testosterone.
AB  - Men with the metabolic syndrome (MetS) and type 2 diabetes (T2D) often have low
      testosterone levels. Elevating low testosterone levels may improve features of
      the MetS and glycemic control. In a single blind, 52-week randomized clinical
      trial, the effects of supervised diet and exercise (D&E) with or without
      transdermal testosterone administration on components of the MetS in hypogonadal
      men with the MetS and newly diagnosed T2D were assessed. A total of 32
      hypogonadal men (total testosterone <12.0 nmol/L) with newly diagnosed T2D and
      with the MetS as defined by the Adult Treatment Panel III and the International
      Diabetes Federation received supervised D&E, but 16 received it in combination
      with testosterone gel (50 mg) once daily (n = 16). No glucose-lowering agents
      were administered prior to or during the study period. Outcome measures were
      components of the MetS as defined by the Adult Treatment Panel III and the
      International Diabetes Federation. Serum testosterone, glycosylated hemoglobin
      (HbA(1c)), fasting plasma glucose, high-density lipoprotein cholesterol,
      triglyceride concentrations, and the waist circumference improved in both
      treatment groups after 52 weeks of treatment. Addition of testosterone
      significantly further improved these measures compared with D&E alone. All D&E
      plus testosterone patients reached the HbA(1c) goal of less than 7.0%; 87.5% of
      them reached an HbA(1c) of less than 6.5%. Based on Adult Treatment Panel III
      guidelines, 81.3% of the patients randomized to D&E plus testosterone no longer
      matched the criteria of the MetS, whereas 31.3% of the D&E alone participants
      did. Additionally, testosterone treatment improved insulin sensitivity,
      adiponectin, and high-sensitivity C-reactive protein. Addition of testosterone to
      supervised D&E results in greater therapeutic improvements of glycemic control
      and reverses the MetS after 52 weeks of treatment in hypogonadal patients with
      the MetS and newly diagnosed T2D.

PMID- 19578133
TI  - Measurement of testicular volume in smaller testes: how accurate is the
      conventional orchidometer?
AB  - The aim of this study was to evaluate the accuracy of different methods,
      including the Seager orchidometer (SO) and ultrasonography (US), for assessing
      testicular volume of smaller testes (testes volume less than 18 mL). Moreover,
      the equations used for the calculations--the Hansen formula (length [L] x width
      [W](2) x 0.52, equation A), the prolate ellipsoid formula (L x W x height [H] x
      0.52, equation B), and the Lambert equation (L x W x H x 0.71, equation C)--were
      also examined and compared with the gold standard testicular volume obtained by
      water displacement (Archimedes principle). In this study, 30 testes from 15 men,
      mean age 75.3 (+/-8.3) years, were included. They all had advanced prostate
      cancer and were admitted for orchiectomy. Before the procedure, all the testes
      were assessed using SO and US. The dimensions were then input into each equation
      to obtain the volume estimates. The testicular volume by water displacement was
      8.1 +/- 3.5 mL. Correlation coefficients (R(2)) of the 2 different methods (SO,
      US) to the gold standard were 0.70 and 0.85, respectively. The calculated
      testicular volumes were 9.2 +/- 3.9 mL (measured by SO, equation A), 11.9 +/- 5.2
      mL (measured by SO, equation C), 7.3 +/- 4.2 mL (measured by US, equation A), 6.5
      +/- 3.3 mL (measured by US, equation B) and 8.9 +/- 4.5 mL (measured by US,
      equation C). Only the mean size measured by US and volume calculated with the
      Hansen equation (equation A) and the mean size measured by US and volume
      calculated with the Lambert equation (equation C) showed no significant
      differences when compared with the volumes estimated by water displacement (mean
      difference 0.81 mL, P = .053, and 0.81 mL, P = .056, respectively). Based on our
      measurements, we categorized testicular volume by different cutoff values (7.0
      mL, 7.5 mL, 8.0 mL, and 8.5 mL) to calculate a new constant for use in the Hansen
      equation. The new constant was 0.59. We then reexamined the equations using the
      new 0.59 constant, and found that the equation Volume (V) = L x W(2) x 0.59 was
      the best for describing testicular volume among our subjects (difference between
      the new equation and the gold standard of water displacement = 0.19 mL, P =
      .726). We also found that US was more precise in measuring testicular dimensions.
      We propose a new formula, V = L x W(2) x 0.59, to assess the volumes of smaller
      testes.

PMID- 19578134
TI  - Identification of rat prostatic secreted proteins using mass spectrometric
      analysis and androgen-dependent mRNA expression.
AB  - Rats have been used to study the function and development of the mammalian
      prostate. Identification of prostatic secreted proteins is important in order to
      better understand their physiological function. Previous investigations have
      showed that prostatein, cysteine-related protein 1, and kallikrein S3 are in the
      ventral prostate (VP), whereas the proteins probasin, prostate secretory peptide
      94, transglutaminase 4, and carbonic anhydrase II are produced in the lateral
      prostate, dorsal prostate (DP), and anterior prostate. They are also useful
      markers when looking at androgen dependency as well as prostate-specific
      expression. Although some of the rat prostatic proteins have been investigated
      well, the overall protein expression profile of the prostate has not been
      examined. In the present study, the secretions from the rat prostate were
      subjected to 2-dimensional gel electrophoresis followed by mass spectrometric
      analysis. In addition to the previously known proteins, proteome analysis
      revealed several new secreted proteins, including spermine-binding protein and a
      protein similar to immunoglobulin-binding protein. In addition, epididymal
      secreted protein 1 and peroxiredoxin 6 were found in the DP, while glucose
      regulated protein 78 was identified in all lobes of the prostate. Castration of
      the animals led to a decrease in the mRNAs of all of these secreted proteins.
      While the mRNAs of prostatic proteins became almost completely absent in the VP,
      the reductions in the other lobes were limited. A novel view of rat prostate
      secretion from our results should contribute to an understanding of the
      biological functions of the prostate gland.

PMID- 19578135
TI  - Comment on: British Society for Rheumatology and British Health Professionals in
      Rheumatology guideline for the management of rheumatoid arthritis (after the
      first 2 years).

PMID- 19578136
TI  - Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and
      psoriasis treated with methotrexate.
AB  - OBJECTIVE: MTX hepatotoxicity is considered to occur more frequently in patients
      with psoriasis than in patients with RA. However, toxicity guidelines are based
      on reports from studies with small sample sizes and limited follow-up periods.
      The current study's objective was to examine the long-term risk of MTX
      hepatotoxicity based on a database review of patients with RA or psoriasis, and
      to examine whether the two populations differed. METHODS: We conducted a
      retrospective cohort review among members of a large health maintenance
      organization (HMO) in Israel who were diagnosed with either RA (n = 119) or
      psoriasis (n = 690) and who had purchased at least one dose of MTX. Liver
      function analyses were performed serially in these patients during the follow-up.
      All abnormal assays were recorded in the computerized database of the HMO.
      RESULTS: Both groups had hepatic enzyme elevation; the pre-disposing factors
      predictive of liver damage were female gender and a higher cumulative dose of MTX
      (hazard ratios, 1.46 and 1.07, respectively, P < 0.001). Age, concurrent diseases
      and type of disease had no influence on susceptibility to liver damage. No
      statistically significant difference was detected in any abnormal liver function
      test among patients with either RA or psoriasis. CONCLUSION: Our study did not
      corroborate previous findings of significant differences between psoriasis
      patients and RA patients concerning susceptibility to hepatotoxicity from MTX
      therapy. The only significant factor predicting a higher risk of hepatic damage
      was female gender.

PMID- 19578137
TI  - The psychosocial impact of completing childhood cancer treatment: a systematic
      review of the literature.
AB  - OBJECTIVE: To review the results of any published research study examining the
      psychosocial functioning of children who have recently completed cancer
      treatment. METHODS: Five electronic databases were searched (from 1978 to 2008).
      Of 1,734 identified articles, 19 met all inclusion criteria. Four articles
      utilized a qualitative methodology, thirteen utilized a quantitative methodology,
      and two used mixed methods. RESULTS: Children may experience positive
      psychosocial outcomes on treatment completion, including high self-worth, good
      behavioral conduct, and improved mental health and social behavior. However, they
      may also experience significant negative outcomes, including lower levels of
      psychological well-being, mood, liveliness, self-esteem, and motor and physical
      functioning, as well as increased anxiety, problem behaviors, and sleeping
      difficulties. CONCLUSIONS: Completing treatment can be a psychologically complex
      time for children as they wait to make the transition from "cancer patient" to
      long-term "cancer survivor." Further high-quality research targeting the needs of
      these children is warranted.

PMID- 19578138
TI  - Brief report: Don't kiss a sleeping dog: the first assessment of "the blue dog"
      bite prevention program.
AB  - OBJECTIVE: The authors attempted to remedy the current lack of empirically
      evaluated dog-bite prevention programs for children under 7 by assessing
      children's learning success with the "Blue Dog" CD. METHODS: Ninety-six 3-, 4-, 5
      , and 6-year-old children used the interactive CD in an initial exposure phase, a
      training and a testing phase. Half received verbal feedback, and the other half
      additional practice with parents. All children were re-tested after 2 weeks.
      RESULTS: There were significant increases in safe choices after the training
      phase at all ages, with older children performing better than younger children.
      Children still retained their ability to make safe choices after 2 weeks.
      Interestingly, children practicing with parents performed better than others when
      under 6 years. Verbal feedback did not play a role, the CD is equally effective
      without. CONCLUSIONS: Children learned successfully about safe behavior with
      dogs; thus, the CD can help educate children about dog-bite prevention.

PMID- 19578139
TI  - Does low birth weight confer a lifelong respiratory disadvantage?

PMID- 19578140
TI  - Endothelial function in COPD.

PMID- 19578141
TI  - Improved vitamin D status despite allocation to placebo in a tuberculosis
      treatment trial: contamination bias?

PMID- 19578142
TI  - Long-term weight loss and maintenance in morbidly obese individuals with
      obstructive sleep apnea.

PMID- 19578143
TI  - Does itraconazole improve quality of life in severe asthma with fungal
      sensitization?

PMID- 19578144
TI  - Visceral obesity and different phenotypes of COPD.

PMID- 19578148
TI  - Comparative studies on [Pasteurella] testudinis and [P.] testudinis-like bacteria
      and proposal of Chelonobacter oris gen. nov., sp. nov. as a new member of the
      family Pasteurellaceae.
AB  - A collection of 12 strains, isolated from diseased tortoises and tentatively
      identified as [Pasteurella] testudinis-like based on phenotypic characters, was
      compared with three reference strains of [P.] testudinis. All strains could be
      separated from the reference strains with respect to 16S rRNA gene sequences,
      partial sequences of the rpoB housekeeping gene and by phenotypic characters.
      Based upon differences in 16S rRNA and rpoB gene sequences, the new isolates are
      suggested to represent a novel species in a new genus of the family
      Pasteurellaceae Pohl 1981, for which the name Chelonobacter oris gen. nov., sp.
      nov. is proposed. The type strain is 1662(T) (=CCUG 55632(T)=DSM 21392(T)). beta
      Haemolysis and acid production from (+)-l-arabinose, dulcitol, (-)-d-mannitol,
      (+)-d-mannose, trehalose and salicin separated the new strains from members of
      existing genera of the family Pasteurellaceae, in addition to the beta
      galactosidase, urease and alpha-glucosidase reactions. Differences in indole
      production, phosphatase, beta-glucosidase and production of acid from dulcitol
      and trehalose separated C. oris from [P.] testudinis. Several phenotypic
      characters separated C. oris from Bisgaard's taxa 14 and 32.

PMID- 19578149
TI  - Serratia nematodiphila sp. nov., associated symbiotically with the
      entomopathogenic nematode Heterorhabditidoides chongmingensis (Rhabditida:
      Rhabditidae).
AB  - A novel red-pigmented, Gram-negative, motile, fluorescent, rod-shaped strain,
      DZ0503SBS1(T), with a single lateral flagellum, was isolated from the intestine
      of the nematode Heterorhabditidoides chongmingensis. Comparative 16S rRNA gene
      sequence analysis indicated that the strain is a member of the genus Serratia,
      sharing highest sequence similarities with Serratia marcescens subsp. sakuensis
      JCM 11315(T) (99.8 %), S. marcescens subsp. marcescens DSM 30121(T) (99.5 %) and
      Serratia ureilytica LMG 22860(T) (98.3 %). Similarities between the rpoB gene
      sequence of strain DZ0503SBS1(T) and those of S. marcescens subsp. sakuensis JCM
      11315(T), S. marcescens subsp. marcescens DSM 30121(T) and S. ureilytica LMG
      22860(T) were 98.0, 97.4 and 98.3 %, respectively. DNA-DNA hybridization values
      of strain DZ0503SBS1(T) with S. marcescens subsp. sakuensis JCM 11315(T), S.
      marcescens subsp. marcescens DSM 30121(T) and S. ureilytica LMG 22860(T) were
      68.2, 65.1 and 53.0 %, respectively. The major isoprenoid quinone of strain
      DZ0503SBS1(T) was Q-8 and the predominant fatty acids were C(16 : 0) (34.76 %),
      cyclo-C(17 : 0) (20.03 %) and cyclo-C(19 : 0)omega8c (17.24 %). The cyclo-C(19 :
      0)omega8c content (17.24 %) was significantly different from those found in S.
      marcescens subsp. sakuensis JCM 11315(T) and S. marcescens subsp. marcescens DSM
      30121(T). Some characteristics of strain DZ0503SBS1(T), i.e. fluorescence and its
      symbiotic association with nematodes, have not been reported previously in any
      species of the genus Serratia. Phenotypic and biochemical characteristics and
      molecular data show that strain DZ0503SBS1(T) represents a novel species, for
      which the name Serratia nematodiphila sp. nov. is proposed; the type strain is
      DZ0503SBS1(T) (=KCTC 22130(T) =CGMCC 1.6853(T)).

PMID- 19578150
TI  - Enterobacter oryzae sp. nov., a nitrogen-fixing bacterium isolated from the wild
      rice species Oryza latifolia.
AB  - Twelve facultatively anaerobic, endophytic diazotrophs were isolated from surface
      sterilized roots of the wild rice species Oryza latifolia and characterized by
      phenotypic and molecular methods. Six isolates were grouped together as group A
      by phenotypic characters, and this grouping was confirmed by SDS-PAGE whole-cell
      protein patterns and insertion sequence-based PCR (IS-PCR) methods. Phylogenetic
      analysis of the 16S rRNA gene sequence indicated that group A, represented by
      strain Ola 51(T), is closely related to Enterobacter radicincitans D5/23(T) (98.9
      % similarity, except that E. radicincitans D5/23(T) has a 70 bp insertion) and
      Enterobacter cloacae (98.0 % similarity to the type strain). rpoB gene sequence
      analysis also showed strain Ola 51(T) has the highest sequence similarity to E.
      radicincitans DSM 16656(T) (98.3 %), but supported the distinct position.
      Biological and biochemical tests, protein patterns, genomic DNA fingerprinting,
      antibiotic resistance and comparison of cellular fatty acids showed differences
      among group A, E. radicincitans DSM 16656(T) and E. cloacae ATCC 13047(T). DNA
      DNA hybridization distinguished strain Ola 51(T) from closely phylogenetically
      related Enterobacter species. Based on these data, the novel species Enterobacter
      oryzae sp. nov. is proposed, with strain Ola 51(T) (=LMG 24251(T) =CGMCC
      1.7012(T)) as the type strain.

PMID- 19578151
TI  - Spirochaeta dissipatitropha sp. nov., an alkaliphilic, obligately anaerobic
      bacterium, and emended description of the genus Spirochaeta Ehrenberg 1835.
AB  - A novel obligately anaerobic, mesophilic, alkaliphilic spirochaete, strain
      ASpC2(T), was isolated from an anaerobic sediment of alkaline, hypersaline Owens
      Lake in California, USA. The Gram-negative cells are motile, helical in shape and
      0.23 x 8.0-18.0 mum. Growth occurs within the following ranges: 13-41 degrees C,
      with optimal growth at 35 degrees C; 1-3 % (w/v) NaCl, with optimal growth at 2 %
      (w/v) NaCl; and pH 7.8-10.5, with optimal growth at pH 10.0. The novel isolate is
      strictly alkaliphilic and requires high concentrations of carbonate ions in the
      medium. It utilizes some sugars, some organic acids, some amino acids, Casamino
      acids, yeast extract and peptone. The main end products of glucose fermentation
      are CO(2) and acetate. Strain ASpC2(T) is resistant to kanamycin and rifampicin,
      but sensitive to ampicillin, chloramphenicol, gentamicin and tetracycline. The
      DNA G+C content of the new isolate is 43.8 mol%, its genome size is 6 x 10(8) Da
      and the melting temperature of its genomic DNA is 71 degrees C. DNA-DNA
      hybridization experiments demonstrated 46 % similarity with the phylogenetically
      most closely related species, Spirochaeta asiatica Z-7591(T). On the basis of
      physiological and molecular properties, the new isolate belongs taxonomically to
      a novel species within the genus Spirochaeta, for which the name Spirochaeta
      dissipatitropha sp. nov. is proposed (type strain, ASpC2(T)=ATCC BAA-1083(T)=JCM
      12856(T)). S. dissipatitropha ASpC2(T) is the second strain in the genus (after
      Spirochaeta smaragdinae SEBR 4228(T)) that is able to use proteolysis products as
      the sole energy source, and additional tests have shown that other halo
      alkaliphilic spirochaetes (Spirochaeta americana, Spirochaeta alkalica and
      Spirochaeta africana) are also able to grow on yeast extract alone; therefore, an
      emended description for the genus Spirochaeta is given.

PMID- 19578152
TI  - Using MIMIC models to examine the relationship between current smoking and early
      smoking experiences.
AB  - INTRODUCTION: The present study expands previous research on early experiences
      with tobacco by using a Multiple Indicator Multiple Causes (MIMIC) model, which
      permits combining indicators tapping into pleasant experiences into one latent
      construct and those indicators of unpleasant experiences into another latent
      construct. METHODS: A sample of 458 participants was recruited via newspaper
      advertisements. Response to early experimentation with cigarettes was assessed
      using the Early Smoking Experiences questionnaire, in which participants were
      asked the following question: "The first time you tried cigarettes, did you
      experience any of the following? (pleasurable and displeasurable sensations
      [overall], pleasurable rush or buzz, dizziness, relaxation, nausea, cough,
      difficulty inhaling)." These experiences were rated on a scale ranging from 1 =
      none to 4 = intense. RESULTS: The MIMIC model revealed that current smoking
      status and age of initial experimentation with cigarettes were significantly
      associated with both early pleasant and unpleasant experiences (p < .05). African
      Americans were less likely than Whites to have early unpleasant experiences (p <
      .05). No association was found between race and early pleasant experiences.
      DISCUSSION: Our findings are consistent with the inferences that pleasant
      experiences in response to early experimentation with smoking lead to regular
      smoking and that positive experiences play a stronger role than negative
      experiences in the transition to regular smoking. Our study also demonstrates
      that the MIMIC model is pertinent and practicable in nicotine and smoking
      research. We recommend it as a useful tool for identifying endophenotypes related
      to nicotine dependence and tobacco use latent constructs.

PMID- 19578153
TI  - Olfactory nerve recovery following mild and severe injury and the efficacy of
      dexamethasone treatment.
AB  - To investigate factors that influence the degree of neural regeneration and
      recovery, we studied 2 olfactory nerve injury models. Transection of the
      olfactory nerves along the surface of the olfactory bulb was performed in OMP-tau
      lacZ mice using either a flexible Teflon blade (mild injury) or a stainless steel
      blade (severe injury). Histological assessment of recovery within the olfactory
      bulb was made at 5, 14, and 42 days after injury. We used X-gal staining to label
      the degenerating and regenerating olfactory nerve fibers and immunohistochemical
      staining to detect the presence of reactive astrocytes and macrophages. Areas of
      injury-associated tissue were significantly smaller in the mild injury model, and
      at 42 days, the regenerated nerves had reestablished connections to the
      glomerular layer of the bulb. With severe injury, there were larger areas of
      injury-associated tissue, more astrocytes and macrophages, and a decrease in
      regenerated nerve fibers. When dexamethasone (DXM) was injected after severe
      injury, there was a significant reduction in injury-associated tissue, better
      nerve recovery, and fewer astrocytes and macrophages. These results demonstrate
      that recovery in the olfactory system varies with the severity of injury and that
      DXM treatment may have therapeutic value by reducing injury-associated tissue and
      improving recovery outcome.

PMID- 19578154
TI  - Inhibition of p38-MAPK potentiates cisplatin-induced apoptosis via GSH depletion
      and increases intracellular drug accumulation in growth-arrested kidney tubular
      epithelial cells.
AB  - We were interested in analyzing the regulation by mitogen-activated protein
      kinases (MAPKs) of cisplatin-provoked toxicity in epithelial renal tubule cell
      lines, when assayed under culture conditions (cell confluence plus serum
      deprivation), which mimic the characteristics of a nonproliferating epithelium.
      Under these restrictive growth conditions, cisplatin induced apoptosis with lower
      efficacy than in exponentially growing cells, and decreased p38-MAPK
      phosphorylation in NRK-52E and other (LLC-PK1, MDCK, HK2) cell lines. Moreover,
      cisplatin-provoked apoptosis was potentiated by cotreatment with p38-MAPK
      specific inhibitors (SB203580, SB220025) or transfection with a kinase-negative
      mutant of MKK6, whereas c-Jun NH2-terminal kinase or extracellular signal
      regulated kinase/MAPK and ERK Kinase inhibitors were ineffective. By contrast,
      when applied to exponentially growing cells, cisplatin stimulated p38-MAPK
      phosphorylation and apoptosis, was attenuated by kinase inhibitors. Treatment of
      confluent/serum-deprived cells with cisplatin caused mitochondrial transmembrane
      potential disruption and activated the mitochondrial apoptotic pathway, as
      indicated by the decrease in Bcl-X(L) expression, increase in Bax expression and
      cytochrome c release, and these effects were potentiated by cotreatment with
      SB203580. Treatment of confluent/serum-deprived cells with cisplatin plus
      SB203580 decreased the intracellular reduced glutathione (GSH) content, and
      increased intracellular cisplatin accumulation as well as cisplatin binding to
      DNA. Cotreatment with the GSH-depleting agent D,L-buthionine-R,S-sulfoximine also
      potentiated cisplatin-provoked apoptosis. In summary, p38-MAPK inhibition
      potentiates cisplatin-provoked apoptosis in growth-arrested epithelial renal
      tubule cells, a result that may be explained at least in part by GSH depletion
      and drug transport alteration.

PMID- 19578155
TI  - A profound role for the expansion of trypsin-like serine protease family in the
      evolution of hematophagy in mosquito.
AB  - The trypsin-like serine protease (Tryp_SPc) family is ubiquitous in animals and
      plays diverse roles, especially in the digestive system, in different phyla. In
      the mosquito, some Tryp_SPc proteases make important contributions to the
      digestion of the blood meal. Here, we have defined the complete Tryp_SPc gene
      repertoire in the genome of the malaria mosquito, a repertoire that has expanded
      remarkably compared with that of Drosophila. Phylogenetic analysis also indicates
      that the large-scale lineage-specific expansion occurred leading to mosquitoes.
      Expression of Tryp_SPc genes elevates after a blood meal, and the expression
      level of genes that belong to subfamilies that specifically expanded on the
      mosquito lineage increased significantly more than genes that belong to
      subfamilies that did not expand in number, suggesting a profound role for the
      Tryp_SPc genes, especially the expanded subfamilies, in the hematophagous trait
      of the mosquito. The mosquito Tryp_SPc genes are mostly distributed in a tandem
      manner on chromosomes, suggesting a role for tandem duplication in the expansion
      of the subfamilies. Furthermore, evidence for positive selection was found for
      some genes. Structural modeling indicates that the positively selected sites
      locate to the surface that is conjugated by protein inhibitors. Our results
      suggest that the expansion and diversification of the Tryp_SPc domain family in
      mosquito was driven by positive selection and helps to explain the adaptive
      hematophagy of the mosquito.

PMID- 19578156
TI  - Evolution of plant MADS box transcription factors: evidence for shifts in
      selection associated with early angiosperm diversification and concerted gene
      duplications.
AB  - Phylogenomic analyses show that gene and genome duplication events have led to
      the diversification of transcription factor gene families throughout the
      evolutionary history of land plants and that gene duplications have played an
      important role in shaping regulatory networks influencing key phenotypic
      characters including floral development and flowering time. A molecular
      evolutionary investigation of the mode and tempo of selection acting on the
      angiosperm MADS box AP1/SQUA, AP3/PI, AG/AGL11, and SEP gene subfamilies revealed
      site-specific patterns of shifting evolutionary constraint throughout angiosperm
      history. Specific positions in the four canonical MADS box gene regions,
      especially K domains and C-terminal regions of all four of these MADS box gene
      subfamilies exhibited clade-specific shifts in selective constraint following
      concerted duplication events. Moreover, the frequency of site-specific shifts in
      constraint was correlated with gene duplications and early angiosperm
      diversification. We hypothesize that coevolution among interacting MADS box
      proteins may be responsible for simultaneous increases in the ratio of
      nonsynonymous to synonymous substitutions (d(N)/d(S) = omega) early in angiosperm
      history and following concerted duplication events.

PMID- 19578157
TI  - Interrogating 11 fast-evolving genes for signatures of recent positive selection
      in worldwide human populations.
AB  - Different signatures of natural selection persist over varying time scales in our
      genome, revealing possible episodes of adaptative evolution during human history.
      Here, we identify genes showing signatures of ancestral positive selection in the
      human lineage and investigate whether some of those genes have been evolving
      adaptatively in extant human populations. Specifically, we compared more than
      11,000 human genes with their orthologs in chimpanzee, mouse, rat, and dog and
      applied a branch-site likelihood method to test for positive selection on the
      human lineage. Among the significant cases, a robust set of 11 genes was then
      further explored for signatures of recent positive selection using single
      nucleotide polymorphism (SNP) data. We genotyped 223 SNPs in 39 worldwide
      populations from the HGDP-CEPH diversity panel and supplemented this information
      with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on
      each gene. After exploring the allele frequency spectrum, population
      differentiation and the maintenance of long unbroken haplotypes, we found signals
      of recent adaptative phenomena in only one of the 11 candidate gene regions.
      However, the signal of recent selection in this region may come from a different,
      neighboring gene (CD5) rather than from the candidate gene itself (VPS37C). For
      this set of positively selected genes in the human lineage, we find no indication
      that these genes maintained their rapid evolutionary pace among human
      populations. Based on these data, it therefore appears that adaptation for human
      specific and for population-specific traits may have involved different genes.

PMID- 19578158
TI  - Mitochondrial insertions into primate nuclear genomes suggest the use of numts as
      a tool for phylogeny.
AB  - Homoplasy-free characters are a valuable and highly desired tool for molecular
      systematics. Nuclear sequences of mitochondrial origin (numts) are fragments of
      mitochondrial DNA that have been transferred into the nuclear genome. numts are
      passively captured into genomes and have no transposition activity, which
      suggests they may have utility as phylogenetic markers. Here, five fully
      sequenced primate genomes (human, chimpanzee, orangutan, rhesus macaque, and
      marmoset) are used to reconstruct the evolutionary dynamics of recent numt
      accumulation in a phylogenetic context. The status of 367 numt loci is used as
      categorical data, and a maximum parsimony approach is used to trace numt
      insertions on different branches of the taxonomically undisputed primate
      phylogenetic tree. The presence of a given numt in related taxa implies
      orthologous integration, whereas the absence of a numt indicates the
      plesiomorphic condition prior to integration. An average rate of 5.65 numts per 1
      My is estimated on the tree, but insertion rates vary significantly on different
      branches. Two instances in which the presence-absence pattern of numts does not
      agree with the phylogenetic tree were identified. These events may be the result
      of either lineage sorting or reversal. Using the numts reported here to
      reconstruct primate phylogeny produces the canonical primate tree topology with
      high bootstrap support. Moreover, numts identified in gorilla Supercontigs were
      used to test the human-chimp-gorilla trichotomy, yielding a high level of support
      for the sister relationship of human and chimpanzee. These analyses suggest that
      numts are valuable phylogenetic markers that can be used for molecular
      systematics. It remains to be tested whether numts are useful at deeper
      phylogenetic levels.

PMID- 19578159
TI  - The chloroplast genomes of the green algae Pedinomonas minor, Parachlorella
      kessleri, and Oocystis solitaria reveal a shared ancestry between the
      Pedinomonadales and Chlorellales.
AB  - The green algae belonging to the Chlorophyta-the lineage sister to that
      comprising the land plants and their charophycean green algal relatives
      (Streptophyta)-have been subdivided into four classes (Prasinophyceae,
      Ulvophyceae, Trebouxiophyceae, and Chlorophyceae). Yet the Pedinomonadales, an
      assemblage consisting of tiny, naked uniflagellates with a second basal body, has
      no clear affiliation with these classes and the branching order of the crown
      chlorophytes remains unknown. To gain an insight into the phylogenetic position
      of the Pedinomonadales and the relationships among the recognized chlorophyte
      classes, we have sequenced the chloroplast genomes of Pedinomonas minor
      (Pedinomonadales) and of two trebouxiophyceans belonging to the Chlorellales,
      Parachlorella kessleri (Chlorellaceae) and Oocystis solitaria (Oocystaceae), and
      compared these genomes with those of previously examined streptophytes and
      chlorophytes, including Chlorella vulgaris (Chlorellaceae). Unlike their
      Chlorella homolog, the three newly investigated chloroplast DNAs (cpDNAs) carry a
      large rRNA-encoding inverted repeat (IR) that divides the genome into large and
      small single-copy regions. In contrast to the situation found for ulvophycean and
      chlorophycean cpDNAs, the gene contents of the IR and single-copy regions are
      strikingly similar to that inferred for the common ancestor of chlorophytes and
      streptophytes. The intronless 98,340-bp Pedinomonas genome is among the
      chlorophyte cpDNAs featuring the smallest size and most ancestral gene
      organization. All 105 conserved genes encoded by this genome are included in the
      gene repertoires of Oocystis (111 genes) and Chlorella (113 genes), with just
      trnR(ccg) missing from Parachlorella cpDNA. Trees inferred from 71 cpDNA-encoded
      genes/proteins of 16 chlorophytes and nine streptophytes showed that Pedinomonas
      is nested in the Chlorellales, a group of algae lacking flagella. This
      phylogenetic conclusion is independently supported by uniquely shared gene
      linkages. We hypothesize that chlorellalean and pedinomonadalean green algae are
      reduced forms of a distant biflagellate ancestor that might have also given rise
      to the other known trebouxiophycean lineages. Our structural cpDNA data suggest
      that the Chlorellales and Pedinomonadales represent a deep branch of core
      chlorophytes, strengthening the notion that the Trebouxiophyceae emerged before
      the Ulvophyceae and Chlorophyceae. Our results further emphasize the importance
      of secondary reduction at both the cellular and genome levels during chlorophyte
      evolution.

PMID- 19578160
TI  - Sialic acid content of tissue-specific gp96 and its potential role in modulating
      gp96-macrophage interactions.
AB  - Cancer-derived heat shock protein gp96 induces a tumor-specific protective immune
      response primarily mediated by cytotoxic T lymphocytes (CTL) directed toward
      cancer-associated peptides associated with gp96. Both innate and adaptive immune
      responses have been demonstrated using a cell culture-based signaling mechanism.
      When used as an extraneous vaccine, one critical interaction which must occur for
      an immune response to be generated is the interaction between gp96 and the
      antigen presenting cell (APC) surface receptors (CD91, SR-A, TLR-2, and TLR-4).
      Our previous study concluded that gp96 purified from various rat and human
      prostate cancers is differentially glycosylated based on the amino and neutral
      monosaccharide content, and it was postulated that the monosaccharides may play a
      role in its biological activity. In this report, we report differences in the
      cancer-specific sialic acid content of gp96 purified from normal rat prostate
      compared to two rat prostate cancers, MAT-LyLu and Dunning G, as well as between
      two human prostate cancer cells, LnCaP and DU145. We also examined the modulatory
      effect of sialic acid residues on the binding of gp96 to APCs and its subsequent
      activation. Our results supported the contention that significant differences in
      the sialic acid content exist between Dunning G, MAT-LyLu, and normal rat
      prostate gp96, which affected its binding and biochemical activity to APCs. We
      therefore postulate that varied glycans of HPS96, a hitherto neglected structural
      component, may play a pivotal role in its anticancer activity. We suggest that
      construction of the glycan tree is a key to identification of the necessary and
      sufficient elements in the structure-function activity of HSP96.

PMID- 19578162
TI  - Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses
      COX-2 expression.
AB  - Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis,
      plays a key role in inflammation and circulatory homeostasis. Peroxisome
      proliferator-activated receptors (PPARs) are ligand-dependent transcription
      factors belonging to the nuclear receptor superfamily and are involved in the
      control of COX-2 expression, and vice versa. Here, we show that COX-2 promoter
      activity was suppressed by essential oils derived from thyme, clove, rose,
      eucalyptus, fennel, and bergamot in cell-based transfection assays using bovine
      arterial endothelial cells. Moreover, from thyme oil, we identified carvacrol as
      a major component of the suppressor of COX-2 expression and an activator of
      PPARalpha and gamma. PPARgamma-dependent suppression of COX-2 promoter activity
      was observed in response to carvacrol treatment. In human macrophage-like U937
      cells, carvacrol suppressed lipopolysaccharide-induced COX-2 mRNA and protein
      expression, suggesting that carvacrol regulates COX-2 expression through its
      agonistic effect on PPARgamma. These results may be important in understanding
      the antiinflammatory and antilifestyle-related disease properties of carvacrol.

PMID- 19578161
TI  - Contributions of quantitative proteomics to understanding membrane microdomains.
AB  - Membrane microdomains, e.g., lipid rafts and caveolae, are crucial cell surface
      organelles responsible for many cellular signaling and communication events,
      which makes the characterization of their proteomes both interesting and
      valuable. They are large cellular complexes comprised of specific proteins and
      lipids, yet they are simple enough in composition to be amenable to modern
      LC/MS/MS methods for proteomics. However, the proteomic characterization of
      membrane microdomains by traditional qualitative mass spectrometry is
      insufficient for distinguishing true components of the microdomains from
      copurifying contaminants or for evaluating dynamic changes in the proteome
      compositions. In this review, we discuss the contributions quantitative
      proteomics has made to our understanding of the biology of membrane microdomains.

PMID- 19578163
TI  - Cholesterol absorption and synthesis markers in individuals with and without a
      CHD event during pravastatin therapy: insights from the PROSPER trial.
AB  - Cholesterol homeostasis, defined as the balance between absorption and synthesis,
      influences circulating cholesterol concentrations and subsequent coronary heart
      disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in
      cholesterol biosynthesis and is efficacious in lowering CHD events and mortality.
      Nonetheless, CHD events still occur in some treated patients. To address
      differences in outcome during pravastatin therapy (40 mg/day), plasma markers of
      cholesterol synthesis (desmosterol, lathosterol) and fractional cholesterol
      absorption (campesterol, sitosterol) were measured, baseline and on treatment, in
      the Prospective Study of Pravastatin in the Elderly at Risk trial participants
      with (cases, n = 223) and without (controls, n = 257) a CHD event. Pravastatin
      therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL
      cholesterol concentrations to a similar extent in cases and controls. Decreased
      concentrations of the cholesterol synthesis markers desmosterol (-12% and -11%)
      and lathosterol (-50% and -56%) and increased concentrations of the cholesterol
      absorption markers campesterol (48% and 51%) and sitosterol (25% and 26%) were
      observed on treatment, but the magnitude of change was similar between cases and
      controls. These data suggest that decreases in cholesterol synthesis in response
      to pravastatin treatment were accompanied by modest compensatory increases in
      fractional cholesterol absorption. The magnitude of these alterations were
      similar between cases and controls and do not explain differences in outcomes
      with pravastatin treatment.

PMID- 19578164
TI  - C-reactive protein improves risk prediction in patients with acute coronary
      syndromes.
AB  - AIMS: Elevated C-reactive protein level is a risk marker in patients with acute
      coronary syndromes (ACSs), but current risk score systems do not consider this
      factor. We studied the incremental predictive value of adding C-reactive protein
      to the Global Registry of Acute Coronary Events (GRACE) risk score. METHODS AND
      RESULTS: Characteristics, treatments and 30-day mortality were recorded for
      1408/1901 consecutive ACS patients. Changes in global model fit, discrimination,
      calibration, and reclassification were evaluated upon addition of C-reactive
      protein to the GRACE risk score. High-C-reactive protein patients (C-reactive
      protein >22 mg/L, 4th quartile of C-reactive protein) were older, had more
      comorbidities and worse haemodynamic conditions, received less recommended
      treatment, and had a four-fold higher 30 day mortality. Multivariable analysis
      demonstrated high-C-reactive protein as an important and independent predictor of
      mortality. Addition of high-C-reactive protein in the GRACE model modestly
      improved global fit, discriminatory capacity (c-statistic from 0.795 to 0.823),
      and calibration. Patients were divided into four groups according to GRACE risk
      score prediction: <1, 1 to <5, 5 to <10, and >or=10%. The model with high-C
      reactive protein allowed adequate reclassification in 12.2%. CONCLUSION: Elevated
      C-reactive protein level is a modest but independent predictive factor of 30-day
      mortality in ACS patients, even after adjustment for co-morbidities, haemodynamic
      conditions, and treatment. Combined with the GRACE risk score, C-reactive protein
      information improves risk classification.

PMID- 19578165
TI  - Magnetic resonance imaging and response to cardiac resynchronization therapy:
      relative merits of left ventricular dyssynchrony and scar tissue.
AB  - AIM: To assess the relative value of a novel measure of left ventricular (LV)
      dyssynchrony derived from magnetic resonance imaging (MRI) and the extent of scar
      tissue for prediction of response to cardiac resynchronization therapy (CRT).
      METHODS AND RESULTS: Thirty-five heart failure patients scheduled for CRT were
      included. Left ventricular dyssynchrony was defined as the standard deviation of
      16 segment time-to-maximum radial wall thickness (SDt-16) obtained from a cine
      set of short-axis slices. Delayed-enhanced MRI was performed for scar analysis.
      Echocardiography was used to determine response to CRT (reduction > or =15% in LV
      end-systolic volume 6 months after implantation). At follow-up, 21 patients (60%)
      were classified as responders. On MRI, SDt-16 was significantly higher in
      responders compared with non-responders (median 97 vs. 60 ms, P < 0.001), whereas
      the total extent of scar was larger in non-responders (median 35% vs. 3% in
      responders, P < 0.001). At the logistic regression analysis, SDt-16 was directly
      associated (OR = 6.3, 95% CI 3.1-9.9, P < 0.001) and the total extent of scar was
      inversely associated (OR = 0.52, 95% CI 0.43-0.87, P < 0.001) with response to
      CRT. CONCLUSION: Magnetic resonance imaging offers the unique opportunity to
      assess LV dyssynchrony and scar extent in a single session. Both these parameters
      are important predictors of echocardiographic response to CRT.

PMID- 19578166
TI  - First locus for primary pulmonary vein stenosis maps to chromosome 2q.
AB  - AIMS: Primary pulmonary vein stenosis (PVS) is a rare cardiac abnormality that
      exhibits a high morbidity and mortality rate. The disease is characterized by
      obstruction of the pulmonary venous blood flow owing to congenital hypoplasia of
      individual extra-pulmonary veins. We describe a consanguineous Turkish family
      with four affected siblings with primary PVS in association with prenatal
      lymphatic abnormalities. We aimed to map the first gene for primary PVS. METHODS
      AND RESULTS: Patients had extensive cardiological examinations including
      electrocardiograms, echocardiograms, ventilation-perfusion scans, and cardiac
      catheterizations. All patients died before the age of 16 months because of severe
      progressive primary PVS. Chromosomal analysis revealed normal karyotypes. We
      performed a genome-wide linkage analysis using 250 K single nucleotide
      polymorphism arrays and found the first locus for primary PVS on chromosome 2q35
      2q36.1 [multipoint logarithms (base 10) of odds (LOD) scores 3.6]. By fine
      mapping with microsatellite markers, we confirmed the homozygous region that
      extended 6.6 Mb (D2S164-D2S133). Sequencing 12 (188 exons) of the 88 genes from
      the region revealed no disease-causing sequence variations. CONCLUSION: Our
      findings open perspectives for the identification of the genetic cause(s) leading
      to PVS, which might contribute to elucidate the pathological mechanisms involved
      in this disorder.

PMID- 19578168
TI  - Doing the right thing at the right time: is there more to pulmonary valve
      replacement than meets the eye?

PMID- 19578167
TI  - Increase in end-systolic volume after exercise independently predicts mortality
      in patients with coronary heart disease: data from the Heart and Soul Study.
AB  - AIMS: The predictive value of changes in global left ventricular (LV) size after
      exercise has not been studied. Left ventricular end-systolic volume (ESV) is a
      relatively load-independent echocardiographic marker of contractility that is
      easily measured. We investigated the role of the change in ESV at rest and after
      peak exercise on mortality among patients with stable coronary heart disease
      (CHD). METHODS AND RESULTS: We performed exercise treadmill testing with stress
      echocardiography in 934 ambulatory subjects with CHD. End-systolic volume was
      measured immediately before and after exercise using 2D echocardiography. We
      defined ESV reversal as an increase in ESV after exercise, and we examined the
      association of ESV reversal with all-cause mortality during a median follow-up of
      3.92 years. Of the 934 participants, 199 (21%) had ESV reversal. At the end of
      follow-up, mortality was higher among participants with ESV reversal than those
      without (26 vs. 11%; P < 0.001). After adjustment for clinical covariates, ESV
      reversal remained predictive of all-cause mortality (HR 2.0; 95% CI 1.4-2.9; P =
      0.001). The association of ESV reversal with mortality also persisted after
      adjustment for exercise-induced wall-motion abnormalities (HR 1.7; 95% CI 1.1
      2.3, P = 0.006). To determine if the effect of ESV reversal was independent from
      other echocardiographic measurements, we created a separate model adjusting for
      resting LV ejection fraction, ESV, end-diastolic volume, and LV mass. End
      systolic volume reversal was the only significant predictor of mortality in this
      model (HR 2.1, 95% CI 1.4-3.0, P < 0.001). CONCLUSION: End-systolic volume
      reversal is a novel parameter that independently predicts mortality in patients
      with CHD undergoing exercise treadmill echocardiography, even after adjustment
      for a wide range of clinical, echocardiographic, and treadmill exercise
      variables. Because measurement of ESV is simple, reproducible, and requires no
      additional imaging views, identification of ESV reversal during exercise
      echocardiography can provide useful complementary information for risk
      stratification.

PMID- 19578169
TI  - Pollen-specific SKP1-like proteins are components of functional scf complexes and
      essential for lily pollen tube elongation.
AB  - The ubiquitin-proteasome pathway mediates protein degradation and is involved in
      diverse aspects of plant development and differentiation, including pollen tube
      elongation and self-incompatibility. We characterized three lily (Lilium
      longiflorum) SKP1-like genes, LSK1-LSK3, that are specifically expressed in late
      pollen developmental stages and the elongating pollen tube. The encoded peptide
      sequences reveal that LSK1-LSK3 share high identity with Arabidopsis ASK1 and
      contain a putative N-terminal CUL1- and a C-terminal F-box-interacting domain.
      Yeast two-hybrid and in vitro affinity binding assays revealed that the LSKs
      associate with lily CULLIN1. In addition, the LSK genes can functionally
      complement the yeast skp1 deletion mutant YDR328C. To investigate their
      biological functions in pollen tube elongation, an in vivo approach for green
      fluorescent protein (GFP)-tagged dominant-negative LSK1-LSK3 was developed.
      Microprojectile bombardment with N-terminally truncated LSK1-LSK3 (LSK1-LSK3Delta
      GFP) significantly retarded pollen tube elongation in both in vitro germination
      and in vivo self- and cross-pollination after >12 h incubation. Interestingly,
      elongation of pollen tubes harboring overexpressed LSK2Delta-GFP and LSK3Delta
      GFP was substantially inhibited within the self-pollinated styles. The elongation
      of most LSK2Delta-GFP-transformed pollen tubes could germinate only on the
      stigmatic surface of self style and showed statistically significant growth
      arrest as compared with control pollen tubes. Lily exhibits typical gametophytic
      self-incompatibility via an unknown mechanism, but LSK2 and LSK3 may be involved
      in this complex machinery. These results suggest critical roles for LSK1-LSK3 in
      regulating fundamental pollen tube elongation in vitro and in vivo and that the
      26S proteasome-mediated protein pathway plays an important role in pollen tube
      elongation.

PMID- 19578170
TI  - DYNAMIK: a software environment for cell DYNAmics, Motility, and Information
      tracKing, with an application to Ras pathways.
AB  - The emergence of new microscopy techniques in combination with the increasing
      resource of bioimaging data has given fresh impetus to utilizing image processing
      methods for studying biological processes. Cell tracking studies in particular,
      which are important for a wide range of biological processes such as embryonic
      development or the immune system, have recently become the focus of attention.
      These studies typically produce large volumes of data that are hard to
      investigate manually and therefore call for an automated approach. Due to the
      large variety of biological cells and the inhomogeneity of applications, however,
      there exists no widely accepted method or system for cell tracking until today.
      In this article, we present our publicly available DYNAMIK software environment
      that allows users to compute a suit of cell features and plot the trajectory of
      multiple cells over a sequence of frames. Using chemotaxis and Ras pathways as an
      example, we show how users can employ our software to compute statistics about
      cell motility and other cell information, and how to evaluate their test series
      based on the data computed. We see that DYNAMIK's segmentation and tracking
      compares favorably with the output produced by other software packages.

PMID- 19578171
TI  - Comments on sequence normalization of tiling array expression.
AB  - MOTIVATION: Methods to improve tiling array expression signals are needed to
      accurately detect genome features. Royce et al. provide statistical
      normalizations of tile signal based on probe sequence content that promises
      improved accuracy, and should be independently verified. RESULTS: Assessment of
      the sequence content normalization methods identified a problem: confounding of
      probe sequence content with gene structure (intron/exon) sequence content.
      Normalization obscured tile signal changes at gene structure boundaries. This and
      other evidence suggests that simple sequence normalization does not improve
      detection of genes from tile expression data.

PMID- 19578173
TI  - FRED--a framework for T-cell epitope detection.
AB  - Over the last decade, immunoinformatics has made significant progress.
      Computational approaches, in particular the prediction of T-cell epitopes using
      machine learning methods, are at the core of modern vaccine design. Large-scale
      analyses and the integration or comparison of different methods become
      increasingly important. We have developed FRED, an extendable, open source
      software framework for key tasks in immunoinformatics. In this, its first
      version, FRED offers easily accessible prediction methods for MHC binding and
      antigen processing as well as general infrastructure for the handling of antigen
      sequence data and epitopes. FRED is implemented in Python in a modular way and
      allows the integration of external methods. AVAILABILITY: FRED is freely
      available for download at http://www-bs.informatik.uni
      tuebingen.de/Software/FRED.

PMID- 19578172
TI  - Cross-scale, cross-pathway evaluation using an agent-based non-small cell lung
      cancer model.
AB  - We present a multiscale agent-based non-small cell lung cancer model that
      consists of a 3D environment with which cancer cells interact while processing
      phenotypic changes. At the molecular level, transforming growth factor beta
      (TGFbeta) has been integrated into our previously developed in silico model as a
      second extrinsic input in addition to epidermal growth factor (EGF). The main aim
      of this study is to investigate how the effects of individual and combinatorial
      change in EGF and TGFbeta concentrations at the molecular level alter tumor
      growth dynamics on the multi-cellular level, specifically tumor volume and
      expansion rate. Our simulation results show that separate EGF and TGFbeta
      fluctuations trigger competing multi-cellular phenotypes, yet synchronous EGF and
      TGFbeta signaling yields a spatially more aggressive tumor that overall exhibits
      an EGF-driven phenotype. By altering EGF and TGFbeta concentration levels
      simultaneously and asynchronously, we discovered a particular region of EGF
      TGFbeta profiles that ensures phenotypic stability of the tumor system. Within
      this region, concentration changes in EGF and TGFbeta do not impact the resulting
      multi-cellular response substantially, while outside these concentration ranges,
      a change at the molecular level will substantially alter either tumor volume or
      tumor expansion rate, or both. By evaluating tumor growth dynamics across
      different scales, we show that, under certain conditions, therapeutic targeting
      of only one signaling pathway may be insufficient. Potential implications of
      these in silico results for future clinico-pharmacological applications are
      discussed.

PMID- 19578174
TI  - Are complications of implantable defibrillators under-estimated and benefits over
      estimated?

PMID- 19578175
TI  - Mechanism of paroxysmal supraventricular tachycardia with ventriculoatrial
      conduction block.
AB  - Supraventricular tachycardia (SVT) with ventriculoatrial (VA) block. We report
      the case of a 25-year-old patient with paroxysmal SVT and intermittent VA block.
      Atrioventricular nodal re-entrant tachycardia with upper common pathway block and
      orthodromic nodoventricular or nodofascicular re-entrant tachycardia was
      considered in the differential diagnosis. Diagnostic characteristics were most
      compatible with non-re-entrant junctional tachycardia. The arrhythmia was cured
      by ablation at the right atrial posterior septum.

PMID- 19578176
TI  - Acute and long-term outcome of cryoablation therapy of typical atrioventricular
      nodal reentrant tachycardia.
AB  - AIMS: The purpose of this study was to evaluate the safety and efficacy of
      cryoablation in a large series of patients with typical (slow-fast)
      atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS:
      Between 2003 and 2007, 312 patients with typical AVNRT--median age of 53 years
      (range 10-92), 200 women (64%)--underwent cryoablation, using exclusively a 6 mm
      tip catheter tip. Acute success was achieved in 309 of 312 patients (99%). The
      overall recurrence rate was 18 of 309 (5.8%) during a mean follow-up of 673 +/-
      381 days. Sixteen of these patients (89%) were successfully reablated. The
      recurrence rate was 9% in patients with residual dual atrioventricular (AV) nodal
      pathway post-ablation compared with 4% in those with complete elimination of slow
      pathway conduction (P = 0.05). No patient developed permanent AV block.
      CONCLUSION: Cryoablation of AVNRT can be achieved with a high acute success rate
      and a reasonable recurrence rate at long-term follow-up. Complete abolition of
      slow pathway conduction seems to predict better late outcome.

PMID- 19578177
TI  - Cardiac output response to changes of the atrioventricular delay in different
      body positions and during exercise in patients receiving cardiac
      resynchronization therapy.
AB  - AIMS: The aim of this study was to study the haemodynamic effect of
      atrioventricular delay (AVD) modifications within a narrow range in different
      body positions and during exercise in patients receiving cardiac
      resynchronization therapy (CRT). METHODS: The previously optimized AVD was
      shortened and prolonged by 40 ms in 27 CRT patients and 9 controls without heart
      failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as
      the average over different body positions (left-lateral, supine, sitting,
      standing, and exercise). In eight CRT patients with an implantable haemodynamic
      monitor, the estimated pulmonary artery diastolic pressure (ePAD) was analysed.
      RESULTS: The magnitude of CO response to AVD changes was greater in CRT patients
      than in controls (0.25 vs. 0.20 L/min, P<0.05), varied substantially between
      individuals (range: 0.12-0.56 L/min), and correlated with left atrial size
      (r=0.61, P<0.001). On average, AVD shortening decreased CO slightly (0.07+/-0.17
      L/min) and increased ePAD (1.1+/-0.8 mmHg, both P<0.05), whereas prolongation had
      no significant effect. CONCLUSION: The haemodynamic response to AVD modifications
      within a narrow range is larger in CRT patients than in normal controls and
      varies substantially between individuals. These findings suggest that optimal AVD
      tuning is clinically important in selected patients.

PMID- 19578178
TI  - Resistant mutants of Mycobacterium tuberculosis selected in vitro do not reflect
      the in vivo mechanism of isoniazid resistance.
AB  - OBJECTIVES: The high prevalence of isoniazid-resistant Mycobacterium tuberculosis
      is often explained by a high mutation rate for this trait, although detailed
      information to support this theory is absent. We studied the development of
      isoniazid resistance in vitro, making use of a laboratory strain of M.
      tuberculosis. METHODS: Spontaneous isoniazid-resistant mutants were characterized
      by molecular methods allowing identification of the most commonly encountered
      resistance-conferring mutations. Additionally, we determined the in vitro
      mutation rates for isoniazid and rifampicin resistance, and characterized the
      genome of a triple-resistant strain. RESULTS: Results confirm that the in vitro
      mutation rate for isoniazid resistance (3.2 x 10(-7) mutations/cell division) is
      much higher than the rate for rifampicin resistance (9.8 x 10(-9) mutations/cell
      division). However, in the majority of the in vitro mutants katG was partially or
      completely deleted and neither of the two most common in vivo mutations, katG
      S315T or inhA-C(-)15T, were found in 120 isogenic mutants. This implies that
      clinically prevalent resistance mutations were present in <0.8% of isoniazid
      resistant strains selected in vitro (95% CI 0%-2.5%). The triple-resistant strain
      had acquired isoniazid resistance via a 49 kbp deletion, which included katG.
      Apart from previously identified resistance-conferring mutations, three
      additional point mutations were acquired during sequential selection steps.
      CONCLUSIONS: These outcomes demonstrate that the in vivo mechanism of isoniazid
      resistance is not reflected by in vitro experiments. We therefore conclude that
      the high in vitro mutation rate for isoniazid resistance is not a satisfactory
      explanation for the fact that isoniazid monoresistance is significantly more
      widespread than monoresistance to rifampicin.

PMID- 19578179
TI  - A genome-wide association study of acenocoumarol maintenance dosage.
AB  - Several genome-wide association studies have been performed on warfarin. For
      acenocoumarol, the most frequently used coumarin in many countries worldwide,
      pharmacodynamic influences are expected to be comparable. Pharmacokinetics
      however might differ. We aimed to confirm known or identify new genetic variants
      contributing to interindividual variation on stabilized acenocoumarol dosage by a
      GWAS. The index population consisted of 1451 Caucasian subjects from the
      Rotterdam study and results were replicated in 287 subjects from the Rotterdam
      study extended cohort. Both cohorts were genotyped on the Illumina 550K Human Map
      SNP array. From polymorphisms tested for association with acenocoumarol dosage,
      35 single nucleotide polymorphisms (SNPs) on chromosome 16 and 18 SNPs on
      chromosome 10 reached genome-wide significance. The SNP with the lowest P-value
      was rs10871454 on chromosome 16 linked to SNPs within the vitamin K epoxide
      reductase complex subunit 1 (VKORC1) (P = 2.0 x 10(-123)). The lowest P-value on
      chromosome 10 was obtained by rs4086116 within cytochrome P450 2C9 (CYP2C9) (P =
      3.3 x 10(-24)). After adjustment for these SNPs, the rs2108622 polymorphism
      within cytochrome P450 4F2 (CYP4F2) gene on chromosome 19 reached genome-wide
      significance (P = 2.0 x 10(-8)). On chromosome 10, we further identified genetic
      variation in the cytochrome P450 2C18 (CYP2C18) gene contributing to variance of
      acenocoumarol dosage. Thus we confirmed earlier findings that acenocoumarol
      dosage mainly depends on polymorphisms in the VKORC1 and CYP2C9 genes. Besides
      age, gender, body mass index and target INR, one polymorphism within each of the
      VKORC1, CYP2C9, CYP4F2 and CYP2C18 genes could explain 48.8% of acenocoumarol
      dosage variation.

PMID- 19578188
TI  - Equine disease surveillance, January to March 2009.

PMID- 19578180
TI  - Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse.
AB  - Following a screen for neuromuscular mouse mutants, we identified ostes, a novel
      N-ethyl N-nitrosourea-induced mouse mutant with muscle atrophy. Genetic and
      biochemical evidence shows that upregulation of the novel, uncharacterized
      transient receptor potential polycystic (TRPP) channel PKD1L2 (polycystic kidney
      disease gene 1-like 2) underlies this disease. Ostes mice suffer from chronic
      neuromuscular impairments including neuromuscular junction degeneration,
      polyneuronal innervation and myopathy. Ectopic expression of PKD1L2 in transgenic
      mice reproduced the ostes myopathic changes and, indeed, caused severe muscle
      atrophy in Tg(Pkd1l2)/Tg(Pkd1l2) mice. Moreover, double-heterozygous mice
      (ostes/+, Tg(Pkd1l2)/0) suffer from myopathic changes more profound than each
      heterozygote, indicating positive correlation between PKD1L2 levels and disease
      severity. We show that, in vivo, PKD1L2 primarily associates with endogenous
      fatty acid synthase in normal skeletal muscle, and these proteins co-localize to
      costameric regions of the muscle fibre. In diseased ostes/ostes muscle, both
      proteins are upregulated, and ostes/ostes mice show signs of abnormal lipid
      metabolism. This work shows the first role for a TRPP channel in neuromuscular
      integrity and disease.

PMID- 19578189
TI  - Effects of variations in the environment, length of journey and type of trailer
      on the mortality and morbidity of pigs being transported to slaughter.
AB  - The month, average air temperature, relative humidity, number of pigs of each sex
      per trailer load, journey time, type of trailer and bedding, and waiting time at
      the processing plant were recorded from 16,323 trailers transporting 2,730,754
      pigs to a packing plant in the USA during a year, together with the numbers of
      pigs that were dead on arrival, injured or unable to walk. The percentage of pigs
      dead on arrival increased at temperatures above 20 degrees C, and the percentage
      of pigs unable to walk increased at temperatures of 5 degrees C or below. The
      journey time and waiting time at the processing plant influenced the percentages
      of dead and injured pigs and pigs unable to walk.

PMID- 19578191
TI  - Comparison of analyses of respiratory gases made with the K4b2 portable and Quark
      laboratory analysers in horses.
AB  - Measurements of minute ventilation (VE) and expired oxygen and carbon dioxide
      fractions (FeO2 and FeCO2) were measured at rest and during exercise in seven
      warmblood horses performing two consecutive standardised incremental treadmill
      exercise tests at submaximal speed, using the portable K4b2 telemetric unit and
      the laboratory Quark metabolic cart in random order. Oxygen consumption (VO2) and
      carbon dioxide production (VCO2) were estimated using the Haldane equation. There
      were no significant differences between the measurements made with the two
      devices. However, VE was overestimated when the horses were cantering at 10 m/s
      in comparison with values available in the literature.

PMID- 19578190
TI  - Pharmacokinetics and efficacy of teicoplanin against intramammary infections in
      sheep.
AB  - The pharmacokinetics of teicoplanin were evaluated in 10 healthy sheep. After
      intravenous injection it showed monophasic behaviour, with a short mean (sd)
      elimination half-life (5 [0.24] hours). After intramuscular injection its
      bioavailability was 100 per cent but it was absorbed slowly; its elimination half
      life was satisfactorily slow (9.23 [0.74] hours). Its efficacy was evaluated in
      26 crossbreed sheep with milk positive to strains of Staphylococcus aureus,
      coagulase-negative staphylococci and Streptococcus agalactiae, and clinical signs
      of disease. In 19 of them a single intramuscular dose of 6 mg/kg bodyweight
      resulted in a complete resolution of the clinical signs, and no microorganisms
      were detected in milk by the fifth day; in the other seven sheep, with more
      severe intramammary infections, three consecutive daily intramuscular doses of 6
      mg/kg bodyweight were necessary. There were no local or systemic side effects and
      no relapses during 30 days after the treatments in any of the sheep.

PMID- 19578192
TI  - Bacterial carriage of computer keyboards in veterinary practices in Scotland.

PMID- 19578193
TI  - Laparoscopic castration in a cryptorchid pygmy goat.

PMID- 19578194
TI  - Endocarditis in a British heifer due to Erysipelothrix rhusiopathiae infection.

PMID- 19578195
TI  - Proposed veterinary union.

PMID- 19578196
TI  - Angiostrongylus vasorum in dogs in the UK.

PMID- 19578197
TI  - Tail docking and microchips.

PMID- 19578198
TI  - Proposed veterinary union.

PMID- 19578199
TI  - Defra's management of bluetongue vaccine stocks.

PMID- 19578200
TI  - Necrotising encephalopathy and porencephaly in lambs.

PMID- 19578202
TI  - [Treatment of abdominal hernias by cellular endoprosthesis].
AB  - Abdominal hernias are the most common conditions requiring surgery. The
      objectives of abdominal hernial repair are to minimize recurrence of the disease.
      The prosthetic hernioplasty, which was introduced by Stoppa and Rives, became one
      of the widely accepted. Long-term results of the surgical treatment using new
      modification of Rives-Stoppa technique were presented. The medical records were
      reviewed of 143 patients who underwent hernial repair. The decrease of
      complications such as infections, seromas, and hematomas, and tissue inflammation
      were reported. This technique is safe with a low risk of complications and a low
      rate of recurrence.

PMID- 19578201
TI  - [Our experience of treatment inguinal hernia].
AB  - Inguinal hernia is the most common of all of all hernia surgical procedures.
      Surgery has generally been recommended for all inguinal hernias. The original
      method of reconstruction of the transverse fascia in patients with inguinal
      hernia was introduced. Treatment results in 1200 patients with inguinal hernias
      were analyzed and 558 (46,5%) cases of right-side inguinal hernia, 426 (35,5 %) -
      left-side inguinal hernia, 96 (8%) - both-sided inguinal hernia, 78 (6,5%) -
      recurrent inguinal hernias, 42 (3,5%) - multiple recurrent hernias, 608 (51%) -
      oblique inguinal hernia, 452 (38%) - straight inguinal hernia, 52 (4%) - oblique
      and straighten duct inguinal hernia, 51 (4%) - combined inguinal hernia (oblique
      and straight ) on one side, 29 (2%) - combined inguinal hernia (oblique on one
      side and straight on the other side), 777 (65%) - free inguinal hernia were
      revealed. Transversal fascia by prolen mesh technique is pathogenetically
      relevant and has shown good results.

PMID- 19578203
TI  - [The peculiarities of formation repetitive AV-fistula].
AB  - The issues concerning the formation of an arteriovenous fistula (AV-fistula)
      remain to be one of the most important in modern vascular surgery and nephrology.
      193 surgically treated patients in the terminal stage of chronic renal
      insufficiency have been analyzed and examined. 136 operations and 57 repeated
      procedures of surgical correction of vascular access or formation of new access
      were performed. The conical vascular prosthesis (diameter 4-6 mm and 5-7 mm;
      length - 40 cm and 60) for appropriate hemodialysis is recommended. In case of
      failure of vascular access for hemodialysis PTFE vascular access grafts as the
      most suitable are recommended.

PMID- 19578204
TI  - [Treatment of postoperative abdominal hernias with polypropylene endoprosthesis].
AB  - The results of the surgical treatment of 82 patients with postoperative abdominal
      hernias were analysed. All of the patients underwent surgery with polypropylene
      endoprosthesis. The choice of a hernioplasty method depended on relative volume
      of postoperative hernia. Middle-sized hernias were indications for reconstructive
      surgery (complete adaptation of muscular and aponeurotic layers was maintained).
      The large and gigantic hernias were indications for correcting surgery (specified
      diastasis of muscular and aponeurotic layers was maintained). In case of lacking
      of peritoneum (30 patients) greater omentum was used for isolation of the net
      from intestinal loops. It is concluded that greater omentum provides good
      extraperitonisation of transplant from intestinal loop and prevents complications
      due to contact of net with abdominal organs. Postoperative complications mainly
      were local and seen in 29% cases. There were no lethal outcomes.

PMID- 19578205
TI  - [Analysies of different methods of treatment of osteoarticular system disorders].
AB  - The aim of the present work was the analyses of different methods of treatment of
      patients with osteoarticular system disorders. The case histories of 80 patients
      aged 25-85 with long cortical bone and backbone damages were studied to reveal
      the best method of treatment. The investigation covered the period from 2004
      2008. It was revealed that osteosynthesis allows to avoid the development of
      osteoporosis and promotes bone reconstruction.

PMID- 19578206
TI  - Detection of tolerance against human chorionic gonadotropin at malignant and
      benign tumors of female reproduction system.
AB  - The main aim of this study was to investigate the possibility of hCG synthesis
      during malignant gynecological tumors and establish the level of tolerance
      against hCG in malignant and benign tumors. We have examined peripheral blood of
      86 patients with malignant and benign tumors of reproductive system and healthy
      donors, aged 42-65 for detection of anti-hCG auto-antibodies and possibility of
      hCG synthesis. Investigation have shown that in case of malignant tumors as auto
      antibody concentration is low and hCG level is high, hCG plays a role of
      autocrine growth factor for tumor cells and maintains the malignancy and tumor
      growth. The existence of auto-antibody indicates that immune system is not
      completely tolerant to hCG. During studies on the effectiveness of anti-tumor
      vaccine, this fact should be taken into consideration.

PMID- 19578207
TI  - [Using Camelyn in stomatology, results and vistas].
AB  - In article are presented results of clinical study treatment of inflammatory
      diseases of parodentium, (gingivitis and periodontitis) with medicine Camelyn.
      Camelyn is local product which was (received) produced from the special sort of
      honey and contains biological high active products. Camelyn possesses with
      immunostimulation, anti- inflammatory action, activates regeneration process, has
      analgesic effect. 56 patients with various forms of disease, with gingivitis 25
      patient, with parodontitis 31 were under clinical observation. Estimation of anti
      inflammatory action of Camelyn was based on dynamics of parameters of PMA index.
      Index was defined before beginning of research as well at the end of observation.
      Had been concluded: (in case of gingivitis and periodontitis) It is more
      functional to use topical-application of Camelyn. 5% ointment was used
      independently - separately as well in combine with other medicine. Observation
      has shown reduction of PMA indexes parameter in average on 1,43-time, and
      reduction of treatment's term on 1-2 days in comparison with control group. The
      received results have confirmed clinical appropriateness to use Camelyn for
      gingivitis, parodontitis and periodontitis in combined treatment.

PMID- 19578208
TI  - [Statistical analysis of stationary treatment of traumatic damages of maxilla
      facial area in free and paid medical care conditions].
AB  - The stationary treatment of traumatic damages of maxilla-facial area in free and
      paid medical treatment is analyzed. The archive data of case histories of 1208
      patients with the traumatic damages of maxilla-facial area in 1977-1991 and in
      1992-2006 years were analyzed. Comparative characteristics of the main
      statistical indicators of treatment in conditions of paid and free medical care
      is given. Deterioration of all main indicators was observed during paid medical
      care (from 1992 to 2006 years) in the background of decline of conditions of
      lives. Since 1991 the increase of civilian trauma (domestic trauma) and decrease
      of sporting accidents and industrial injuries has been mentioned. The rates of
      urgent hospitalization decreased and late hospitalization increased
      significantly.

PMID- 19578209
TI  - [Advantan for therapy of atopic dermatitis].
AB  - Atopic dermatitis is a common, chronic skin disease characterized by dry, itchy
      and easily irritated skin. It occurs most commonly in infants and young children,
      but can persist into adulthood. Severe cases can lead to sleep deprivation,
      chronic bacterial infections, and depression. Along with other allergic diseases,
      its prevalence has grown significantly in recent years. Topical medicines are the
      most common and effective treatment for atopic dermatitis. Drugs taken orally and
      used to suppress the immune system have been converted into an ointment or cream.
      These topical immunosuppressive agents are being used now to treat eczema.
      Advantan (0.1% methylprednisolone aceponate) is indicated for the treatment of
      eczema and other inflammatory skin disorders as a highly effective topical
      corticosteroid. The effect of Advantan in the treatment of atopic dermatitis was
      studied. A clinical study of Advantan ointment involved 26 patients aged between
      6 and 56 years with atopic dermatitis. Positive therapeutic effect was achieved
      in the overwhelming majority of the patients (n=25). It was concluded that
      Advantan ointment produced by Schering AC had marked antiinflammatory and
      antipruritic action. It was convenient to use and well tolerated by the patients.
      It is concluded that Advantan may be used for the treatment of patients with
      atopic dermatitis.

PMID- 19578210
TI  - [Efficacy of lamysil dermgel in treatment of tinea versicolor].
AB  - The fungi of the genus Malassezia are part of normal mycobiota of human and
      mammal skin. As a representative of the normal mycobiota skin warm-blooded
      animals and humans, under certain conditions they can cause pathological process
      including tinea versicolor - a common skin infection. In spite of existence of
      broad-spectrum antibiotics and antifungals for the treatment of skin diseases the
      efficacy of drugs aren't always successful. The aim of the study was to estimate
      efficacy of lamysil dermgel in comparison with clotrimazole in the treatment of
      tinea versicolor. The study population included 43 patients of both sex. The
      diagnosis of tinea versicolor was confirmed by assessment of signs and symptoms,
      test-positive by Balzer and by microscopy, which revealed the presence of fungus
      of the Malassezia genus. By the post treatment examination treatment success had
      been achieved in both groups, but significantly higher percentages was achieved
      in lamysil dermgel group. Treatment success rate in lamysil dermgel group:
      clinical cure - 21 patients (95,45%), mycologic cure - 19 patients (86,3%), full 
      18 patients (81,81%). In clotrimazole group: clinicaly cure - 17 patients
      (80,95%), mycologic cure - 13 patients (61,9%), full - 13 patients (61,9%).The
      results of our study confirm highly antifungal activity of lamysil dermgel
      against tinea versicolor and suggest that it may be more effective then
      clotrimazole, therefore it will be approved for treatment of this dermatosis.

PMID- 19578211
TI  - [Psychological aspects of psychosomatic pathology of large intestine].
AB  - One of the most widespread aspects of psychosomatic pathology of gastrointestinal
      tract is irritable bowel syndrome (IBS). Over 70% of functional pathology of
      large intestine falls at IBS. The aim of the investigation was the assessment of
      depression rate in patients with IBS. Taking into consideration the age of
      individuals, 100 patients 50 men and 50 women aged 21 to 75 years were examined
      by using clinical, psychological and statistic (correlation) analysis to
      determine whether there were relations between clinical manifestations of the
      irritable bowel syndrome and personality. Diarrhea variant of IBS syndrome was
      detected in 17 (34%) men and in 21 (42%) females. Diarrhea and pain variant of
      IBS syndrome was detected in 12 (24%) men and 17 (34%) female. Pain variant of
      IBS syndrome was detected in 5 (10%) men and 12 (24%) females. Constipation
      variant was detected in 16 (32%) men and 3 (6%) female. In 84% of patients with
      IBS was found dysphoria; weight loss and bed appetite - in 44%, insomnia - in
      40%, general lethargy and adynamia - in 80%; loss of interest - in 38%; asthenia 
      in 70%, devoured by guilt - 43%, uncertainty - 80%. Depression in patients with
      IBS was treated with serotonin selective antidepressants. Investigation revealed
      that the best result is achieved with serotonin-selective antidepressant therapy.

PMID- 19578212
TI  - [Serotonin and suicide].
AB  - Suicide has been actual medico-social problem in the majority of countries. The
      impact of the socioeconomic variables on suicide is great. It was determined the
      decrease of the frequency of suicide in the post-Soviet countries in the period
      of "Perestroyka" (1984-1986), and permanent increase in late 80s and in the
      beginning of 90s. The aim of the research is to study depression, suicide
      thoughts and blood serotonin in 30 healthy people (15 females and 15 males from
      20 to 70 years old) by means of BECK questionnaire. The following was determined:
      no depression in 40 % of healthy people; moderate depression of 40% of healthy
      people; light depression in 20 % of healthy people. Suicide thoughts were
      displayed in 30% of healthy people; no suicide readiness was determined. Blood
      serotonin was decreased in 85% of the able people; average level of blood
      serotonin was in 12%, and very high in 3% of healthy people. It is concluded that
      introduction of blood serotonin investigation in clinical laboratories is very
      important for monitoring of many diseases.

PMID- 19578213
TI  - [Relationship between serum blood serotonin and tension--type headache].
AB  - Tension - type headache is one of the widely spread types of idiopathic
      headaches. The pathogenesis of the disease includes depression and change in
      brain serotonin level. The aim of the research is to study the characteristics of
      ache and the level of serotonin in blood serum in tension-type headache. The
      intensity of ache, complex psychometric parameters and the level of serotonin in
      blood serum were investigated in 100 patients (75% females and 25% males from 17
      to 55 years old) with tension-type headache. The average period of the illness
      was 6-5 years. The diagnosis has been determined according to MKGB (2003)
      criteria. According to the duration of anamnesis of ache the patients were
      divided into 3 groups: the first - 66 patients, the second - 24 patients, the
      third - 10 patients with tension-type headache and migraine. Ache status and its
      impact on different spheres of activity were assessed according to international
      150 millimeters visual analogous scale. The research showed that all patients
      with tension-type headache had moderate ache syndrome, depression and anxiety of
      the middle or high rate which were in inverse dependence on serotonin rate in the
      blood. Intensity of episodic tension-type headache (n=24) was 52 mm according to
      visual analogous scale, the high rate of anxiety (51,08+/-4,2 scores), moderate
      rate of depression (12,9 scores according to Bek scale) and tendency of serotonin
      decreasing in blood (205,72+/-6,74 ng ml) was noted. The research of 76 patients
      with chronic tension-type headache with cephalgy intensity according to VASH 62
      mm the high indicators of reactive (46,81+/-2,68 scores) and personal anxiety,
      the rate of depression (22,4+/-1,64 according to Bek scale) were associated with
      the displayed decreasing of serotonin amount in blood (119,38+/-9,42 ng/ml). It
      was concluded that, tension-type headache and moderate ache syndrome leads to
      depression decreased self-control of pain and life quality. The quality of
      serotonin in blood decreases in patients with tension-type headache. The
      relationship between the intensity of pain syndrome, decrease of work capacity,
      life quality, and quantity of serotonin in patients with ageing was revealed. It
      is concluded that serotonin level in blood serum may be considered as pain
      intensity, degree of depression and index of efficacy of depression treatment.
      Serotonin is an extremely important neurohormone and its metabolism further study
      will show new characteristic features of its activity in cerebral neurochemical
      processes. Scientists thought, that the increased activity caused the
      psychological disorder, changes in the mood and depression. But the results of
      the last studies show that the person with the abnormal activity of serotonin
      does not realize the sense of danger and accordingly the main instinct of self
      preservation is broken.

PMID- 19578214
TI  - [Anxiety state in patients during postinsult period with old cerebral
      infarction].
AB  - According to ICD-10 International Statistical Classification of Diseases anxiety
      state is different combination of somatic and mental symptoms of anxiety of
      absence of real menace that is onset attack-like or permanently. Anxious disorder
      is observed in 5-10% of the population, twice more often at woman than at men.
      The lengthening of the postinsult period is observed more often in the structure
      of the patient with old cerebral infarction that is complicated with anxious
      disorder. Diagnostics, treatment and prevention of anxious disorder in the
      postinsult period require elaboration of new approaches by the doctors. It is
      announced that anxious disorder in the postinsult period at such patient may
      reach 60-70%. Researches have been held on the basis of the clinic "Medina" in
      Batumi. The main group consisted of 30 out-patients (14 women and 16 men) between
      41 and 73 years old who experienced cerebral infarction of 3-18 months
      prescription. Patients with pancreatic diabetes and unstable accompanying somatic
      diseases were excluded. Computer or magnetic - resonant tomography of the brain
      was performed to all patients during insult in order to verify the diagnosis; the
      clinical-and-psychological and neurological check up was also performed using
      neurological scale NIH NINDS in order to identify severity of insult as well as
      using the scale "Renkin" to assess the degree of impairment of vital functions.
      Depression was assessed with the help of HDRS (Hamilton depression ration scale).
      The level and presence of anxiety were determined by the scale that assesses the
      level of reactive and personal - anxiety. The following initial data were
      received as a result of research from the patients of the comparing groups before
      treatment: an average age of patients was 55,1+/-1,9 years; prescription of
      cerebral infarction was 6,35+/-1,0 months; severity of cerebral infarction on
      scale NIH NINDS was 2,7+/-0,25 points; invalidation degree on "Renkin" scale was
      1,95+/-0,25 points. Personal anxiety was 85,4+/-7,27 points according to self
      assessment scale, reactive anxiety equaled 86,3+/-7,1 points. Depression evidence
      in comparing groups turned out to be initially high and equaled 14,5+/-2,1
      points. The study revealed cognitive functions according to MMSE at 4 men.
      Therefore, a long effecting social stress leads to development of depression.
      Unemployed people working under constant pressure, living in overpopulated areas
      are the most subject to stress as well as those whose mutual relation with
      associates are broken and who more often gets in disputed situations. The first
      condition in treatment of the anxious disorders is detailed knowledge of the
      patient and his understanding the essence of illness. The necessary information
      and the elementary receptions of treatment for overcoming anxiety and panic
      attacks are given by the doctor. Frequently, the relief comes only that the
      patient realizes that it not illness that is unknown and dangerous to a life, but
      curable anxious disorder. Whenever possible the doctor will advise a relevant
      method of psychotherapy which will help to cope with the problems caused by
      prolonged panic disorder.

PMID- 19578215
TI  - Biogerontologic study of population in some districts of Ajara Autonomous
      Republic.
AB  - The study of genetic markers of aging is of current importance in gerontology.
      Data of long-liver residents of Ajara Autonomous Republic have been investigated
      with the aim of establishing genetic markers associated with longevity. 10 blood
      antigens - A, B, C, c, D, E, e, K, M, N of ABO, Rh-Hr, K, MN blood group systems
      have been investigated. The investigation made it possible to single out group
      erythrocyte pheno- and genotypic variants being in correlative relation with
      longevity. In particular O(I), A(II), K+, M+ belong to such phenotypic groups.
      Distribution of blood groups among different age groups was analysed. Rh antigens
      C, D, E were found to be associated with longevity.

PMID- 19578216
TI  - [Interleukin 2 (Ronkoleukin) and its effect on immune state in children with
      acute hematogenous osteomyelitis].
AB  - The object of the present research was to study the effect of recombinant
      interleukin-2 (Ronkoleikin) on immune system in children with acute hematogenous
      osteomyelitis of long cortical bones. The investigation was conducted on 13-15
      year old 30 patients with acute hematogenous osteomyelitis of long cortical
      bones. It was found that Ronkoleukin in sick children with acute hematogenous
      osteomyelitis of long cortical bones leads to improvement in humoral immune
      system. The pro- and anti inflammatory cytokine content is normalized.

PMID- 19578217
TI  - [Classification and the composition of food fibers].
AB  - Fiber promotes the contractions that keep food moving through the intestine.
      Also, high-fiber foods expand the inside walls of the colon and eases the passage
      of waste. The food and fiber research was conducted. In the article, the
      classification and the composition of food fibers are presented. Multifunctional
      properties of food fiber in the process of digestion are discussed. The
      physiological value of food fibers for the human organism is stressed. Diets high
      in fiber during the entire life are recommended. If a person can't consume enough
      fiber in diet alone, certain stool softening and bulking agents are recommended.
      They can be very useful in preventing and treating digestive tract disorders. The
      analysis of high fiber food sources and world production and consumption of food
      fiber is also presented.

PMID- 19578218
TI  - [Plant the raw material--source of the high-quality food fibers].
AB  - A technology has been developed for obtaining food pectin from the waste products
      (citrus fruits and apples) remaining after juice extraction by the ecologically
      clean and reagent-free method - electrodialysis. Reagent-free, eco-pure
      electrodialysis method made it possible to solve two key problems: ecological -
      withdrawal problems and economic - without the consumption of reagents high
      quality pectin from the worthless raw material is obtained. It's 30% cheaper than
      imported. Studies suggest that to achieve detoxification of the body, it is
      necessary to consume soluble fiber (soluble pectin), ie take lemons and/or
      oranges, as well as all studied apple varieties in the state of technical
      maturity and storage for 6 months. It is advised for the normal functioning of
      the gastrointestinal tract to consume fruits at the state of their technical
      maturity. Moreover, it should be noted that the positive effect in this case will
      be achieved through consumption of raw fruits.

PMID- 19578219
TI  - [The condition of oxidation-antioxidation balance of kidney and suprarenal tissue
      in experimental traumatic shock with white rats and the influence of Plaferon
      LB].
AB  - The aim of the work is the study of the oxidation-ant oxidation balance of kidney
      and suprarenal tissue and the influence on them of Plapherone LB preparation. The
      objects for experiment were 30 white rats which weigh was about 200gr. The
      traumatic shock was reproduced according to Kennon. White rats were divided into
      two groups. In 15 minutes after shock intraperitonealy were made: first group -
      0,3 ml of physiologic solution, second group - Plapherone LB 0,06 mg on 0,3 mg of
      physiologic solution. Separately was studied control group of animals. The
      tissues were studied by the method of electronic paramagnet resonance on RE-1304
      radiometer (Russia). The rough upset of oxidation-antioxidation balance was
      revealed. The use of Plapherone LB in this case promotes the optimization of
      these changes.

PMID- 19578220
TI  - [Influence of antioxidants under polytrauma during traumatic sickness].
AB  - To study protective effect of Plapheron LB during grave traumatic sickness.
      Studied 94 patients with grave polytrauma, who were divided in to two groups of
      47 patients. To I-st group was prescribed ordinary program of intensive therapy
      and to the II-nd group of patients additionally to the ordinary program of
      intensive therapy was made Plapheron LB in dose of 0.028 mg/kg two times a day
      sublingually during ten days. Grave condition of the patient was fixed by RTS
      scale and grave of shock by Skinner scale. Stated that each group was different
      in grave traumatic and shock conditions. Separately was studied group of health
      patients. The study was held by the method of electro-paramagnetic resonance of
      venous blood to admitted to hospital patients and on fifth day of intensive
      therapy. Noted: NO, FeS-NO, Fe(3+)-transpherin, Fe(2+) and Met-Hb. From
      immunology cytokin TNF-alpha was studied by the method of immunopherment. Results
      of study and discussion: Plapheron LB promotes decrease of the process of
      peroxide oxidation of lipids, increases activation of antioxidant ferments,
      stimulates production of nitric oxide and decreases the quantity of
      pyoinflammatory complication from those organs and systems which has no frequent
      effect of medical manipulation.

PMID- 19578221
TI  - [The changes of content of TNF-alpha, nitric oxide and FeS-NO in patients blood
      with traumatic shock under Plaferon LB influence].
AB  - There were examined 40 patients with traumatic shock and 10 healthy blood-donor
      (1-st group). The patients were divided into two groups: patients with traumatic
      shock based on standard program of intensive therapy and patients with traumatic
      shock based on standard program of intensive therapy plus Plaferone LB. The blood
      test was made on 1st and 5th day of stationary treatment. TNF-alpha was examined
      in blood plasma by immunophermetic method and NO, FeS-NO by electro-paramagnetic
      resonance method. It was revealed, that Plapherone LB has no affect on TNF-alpha
      concentration, but it modulates NO concentration.

PMID- 19578222
TI  - [Creation of phytovaleologic drugs].
AB  - This is a new field of knowledge in medical sciences that means "Healthy Way of
      Life". Based on the data of medical plants and on the results of Phytochemical
      and Pharmacological studies, carried out in preliminary experiments, there are
      cultivated compositions of Valeological substances, potentially having radio
      protective activity. As the basis for the selection of raw materials and their
      correlation in mixture, there were taken the data of spontaneous analysis of
      chemical composition having pharmacological (radio protective) activity of
      various compositions. As the result, the types of studied raw materials and their
      parties by weight in total mixture have been defined: Valeological substances 1:
      1. Tea (leaves); 2. Common plantain (leaves); 3. Horse gowan (flowers); 4.
      Blackberry (leaves) 5. Hips; 6. Peppermint (leaves). Valeological substances 2:
      1. Tea (leaves); 2. Dandelion (leaves); 3. Horse gowan (flowers); 4. Knotgrass
      (herbage); 5. Hips; 6. Peppermint (leaves) Experimental studies revealed that the
      most optimal way of brewing tea is rational method. Valeological substances 1 and
      2 (tea with radio protective activity) "Protector" and "Adjara" -
      correspondingly. Technical conditions and technological instructions for radio
      protective tea "Protector" and "Adjara" are created. Pharmacological studies of
      tea "Protector" and "Adjara" have taken place in the Branch of Biological
      University of Buryatia (Academy of Science of Russian Federation) under the
      supervision of Prof. S. M. Nikolaev. Radio protective teas "Protector" and
      "Adjara" is approved by the Ministry of Health Sciences.

PMID- 19578223
TI  - [Radio protective drug production from fresh leaves of Aloe arborescens Mill].
AB  - Nowadays, phytogenous drugs are wildly used as radio protective substances. The
      aim of the research was to study radio protective characteristics of aloe juice
      fraction and to develop new technology for radio protective drug production.
      Technological scheme for getting the drug in two stages. The first stage -
      extraction of juice from fresh leaves; the second stage - extracting bagasse have
      been developed and optimal environment for bagasse extraction are defined:
      Infusion of bagasse with 96 % ethyl spirit (1:1) during 30 minutes, continuation
      of extracting with water on correlation to raw materials 10:1 at temperature of
      70 degrees C during 30 minutes. For the basis of the first series of balanced
      loading there are taken the optimal parameters of extracting process, on the
      basis of which in its turn was developed technological scheme of getting dry
      extract of aloe. Dry extract is a fine-dispersed reddish-yellow (brownish-yellow)
      powder, which can be easily dissolved in warm (40-60 degrees C) water.
      Pharmacological researches were conducted in the Institute of General and
      Experimental Biology, Siberian Branch, Russian. Academy of Sciences. The
      remarkable radio protective effect of the drug was revealed.

PMID- 19578224
TI  - Intermittent or daily short course chemotherapy for tuberculosis in children:
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To compare the effectiveness of intermittent with daily chemotherapy
      (both containing rifampicin) in childhood tuberculosis (age 16yrs) in achieving
      cure significant improvement. DESIGN: Systematic Review and Meta-analysis.
      METHODS: MEDLINE and the Cochrane Library were searched for randomized trials of
      antitubercular regimens containing rifampicin, in children 16 yrs or less with
      tuberculosis. Two reviewers independently assessed trial eligibility and quality.
      Data from full articles of selected studies were independently extracted by two
      authors and analyzed. The odds ratio was obtained for the pooled data in two
      groups (intermittent and daily therapy). OUTCOME VARIABLES: Cure/significant
      improvement, relapse rate and adverse events. RESULTS: Four randomized controlled
      trials comparing twice weekly and daily therapy including 466 children (pulmonary
      439; extrapulmonary 27) met the inclusion criteria. Baseline data were
      comparable. On quality assessment, 3 studies scored 2 and one study scored 3 out
      of 5 points. Per protocol analysis showed that children receiving intermittent
      regimen were less likely to be cured than those receiving daily therapy (OR 0.27;
      95% CI: 0.14, 0.51). The results of intention to treat analysis suggest similar
      trend towards lower cure rates with twice weekly regimen (OR 0.66; 95% CI: 0.23
      1.84). CONCLUSION: Twice weekly intermittent short course therapy is less likely
      to cure tuberculosis in children as compared to daily therapy. There is a need
      for better quality randomized controlled trials for assessing efficacy of
      alternate schedule for intermittent therapy for childhood tuberculosis.

PMID- 19578225
TI  - Cost-effectiveness of supplementary immunization for measles in India.
AB  - OBJECTIVE: This study aims to estimate the incremental cost effectiveness of a
      supplementary immunization activity (SIA) for measles in a district of India with
      measles vaccine coverage equivalent to the National average. DESIGN: A state
      transition model is used to estimate the effect of routine vaccination with
      measles vaccine as well as with measles vaccine during the SIA. The model follows
      each sub-cohort in the target population at respective age (1-5 years) to five
      years of age, using age specific incidence rate and vaccination rate to determine
      the number of cases of measles. Using age specific incidence rates and
      complication rates for measles; deaths and disability adjusted life year (DALY)
      averted is estimated. RESULTS: Using base-case assumptions, an estimated 65479
      cases of measles and 1637 deaths due to measles will be prevented in a span of
      four years from a single supplementary immunization activity in a pediatric
      population (1-5 years of age) of size 839,473. The cost per measles vaccine dose
      delivered is INR 30. Using base case analysis the cost to avert a death is INR
      15381 and the cost per disability adjusted life year (DALY) averted is INR 430.
      CONCLUSIONS: Supplementary immunization activity for measles is cost-effective.
      However, this cannot be considered superior to a second dose of measles in
      routine immunization.

PMID- 19578226
TI  - Bubble CPAP for respiratory distress syndrome in preterm infants.
AB  - OBJECTIVES: To ascertain the immediate outcome of preterm infants with
      respiratory distress syndrome (RDS) on Bubble CPAP and identify risk factors
      associated with its failure. STUDY DESIGN: Prospective analytical study.
      SUBJECTS: Inborn preterm infants (gestation 28 to 34 weeks) admitted to the NICU
      with respiratory distress and chest X ray suggestive of RDS. INTERVENTION: Bubble
      CPAP with bi-nasal prongs. PRIMARY OUTCOME: CPAP failures infants requiring
      ventilation in the first one week. RESULTS: 56 neonates were enrolled in the
      study. 14 (25%) babies failed CPAP. The predictors of failure were; no or only
      partial exposure to antenatal steroids, white-out on the chest X-ray, patent
      ductus arteriosus, sepsis/pneumonia and Downes score > 7 or FiO2 > or = 50% after
      15-20 minutes of CPAP. Other maternal and neonatal variables did not influence
      the need for ventilation. Rates of mortality and duration of oxygen requirement
      was significantly higher in babies who failed CPAP. Only two infants developed
      pneumothorax. No baby had chronic lung disease. CONCLUSION: Infants with no or
      partial exposure to antenatal steroids, white-out chest X-ray, patent ductus
      arteriosus, sepsis/pneumonia and those with higher FiO2 requirement after initial
      stabilization on CPAP are at high risk of CPAP failure (needing mechanical
      ventilation). Bubble CPAP is safe for preterm infants with RDS.

PMID- 19578227
TI  - Light emitting diodes versus compact fluorescent tubes for phototherapy in
      neonatal jaundice: a multi center randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether light-emitting diode (LED) phototherapy is as
      efficacious as compact fluorescent tube (CFT) phototherapy for the treatment of
      non-hemolytic jaundice in healthy term and late preterm neonates. STUDY DESIGN:
      Multi centre open label randomized controlled trial. SETTING: Four tertiary care
      neonatal units. SUBJECTS: Healthy term and late preterm neonates with non
      hemolytic jaundice. INTERVENTION: Single-surface LED or CFT phototherapy. PRIMARY
      OUTCOME VARIABLE: Duration of phototherapy. RESULTS: A total of 272 neonates were
      randomized to receive LED (n=142) or CFT (n=130) phototherapy. The baseline
      demographic and biochemical variables were similar in the two groups. The median
      duration of phototherapy (IQR) in the two groups was comparable (26 (22-36) h vs.
      25(22-36) h; P=0.44). At any time point, a similar proportion of neonates were
      under phototherapy in the two groups (log-rank test, P=0.38). The rate of fall of
      serum total bilirubin (STB) during phototherapy and the incidence of failure of
      phototherapy were also not different. An equal proportion of neonates had a
      rebound increase in STB needing restarting of phototherapy. Side effects were
      rare, comparable in the two groups and included hypothermia, hyperthermia, rash,
      skin darkening and dehydration. CONCLUSIONS: LED and CFT phototherapy units were
      equally efficacious in the management of non-hemolytic hyperbilirubinemia in
      healthy term and late preterm neonates.

PMID- 19578228
TI  - Oxidative stress and anti-oxidative defense in schoolchildren residing in a
      petrochemical industry environment.
AB  - OBJECTIVE: To evaluate the possible relationship between industrial air pollution
      and oxidative stress in schoolchildren by comparing parameters from children
      residing in two nearby localities with contrasting environmental conditions.
      PARTICIPANTS: 42 schoolchildren (12-15 years) from Pancevo (site of Serbias
      largest petrochemical installation) formed the exposed group. 82 schoolchildren
      from Kovacica village, located 30 km north of Pancevo, formed the non-exposed
      group. METHODS: Oxidative stress status, anti-oxidative defense parameters,
      paraoxonase-1 status, lipid status, glucose concentration and leukocyte counts
      were compared in two groups. RESULTS: The children from Pancevo showed higher
      level of oxidative stress demonstrated by an elevated malondialdehyde
      concentration (P <0.001) and decreased superoxide dismutase activity (P<0.01) in
      comparison to the non-exposed group. CONCLUSIONS: The results suggested a
      relationship between the presence of air pollutants and increased oxidative
      stress in schoolchildren residing in an industrial environment.

PMID- 19578229
TI  - Single dose azithromycin versus ciprofloxacin for cholera in children: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the clinical and bacteriological success of single dose
      treatment with azithromycin and ciprofloxacin in children with cholera. DESIGN:
      Randomized, open labelled, clinical controlled trial. SETTING: Tertiary care
      hospital. PARTICIPANTS: 180 children between 2-12 years, having watery diarrhea
      for < or = 24 hr and severe dehydration, who tested positive for Vibrio cholerae
      by hanging drop examination or culture of stool. INTERVENTION: Azithromycin 20
      mg/kg single dose (n=91) or Ciprofloxacin 20 mg/kg single dose (n=89).
      Dehydration was managed according to WHO guidelines. MAIN OUTCOME MEASURES:
      Clinical success (resolution of diarrhea within 24 hr) and bacteriological
      success (cessation of excretion of Vibrio cholerae by day 3). Secondary outcome
      variables included duration of diarrhea, duration of excretion of Vibrio cholerae
      in stool, fluid requirement, and proportion of children with clinical or
      bacteriological relapse. RESULTS: The rate of clinical success was 94.5% (86/91)
      in children treated with Azithromycin and 70.7% (63/89) in those treated with
      Ciprofloxacin [RR (95% CI)=1.34 (1.16-1.54); P< 0.001]. Bacteriological success
      was documented in 100% (91/91) children in Azithromycin group compared to 95.5%
      (85/89) in Ciprofloxacin group [RR (95% CI)=1.05 (1.00 -1.10); P=0.06]. Patients
      treated with Azithromycin had a shorter duration of diarrhea [mean(SD) 54.6
      (18.6) vs 71.5 (29.6) h; mean difference (95% CI) 16.9 (9.6 -24.2); P<0.001] and
      lesser duration of excretion of Vibrio cholerae [mean(SD) 34.6 (16.3) vs 52.1
      (29.2) h; mean difference (95% CI) 17.5 (0.2 -24.7), P<0.001] in children treated
      with Azithromycin vs Ciprofloxacin. The amount of intravenous fluid requirement
      was significantly less among subjects who received Azithromycin as compared to
      those who received Ciprofloxacin [mean(SD) 4704.7(2188.4) vs 3491.1(1520.5) mL;
      Mean difference (95% CI) 1213(645.3 - 1781.9); P<0.001]. Proportion of children
      with bacteriological relapse was comparable in two groups [6.7% (6/89) vs 2.2%
      (2/91); RR (95% CI) 0.95 (0.89 -1.01); P=0.16]. None of the children in either
      group had a clinical relapse. CONCLUSION: Single dose azithromycin is superior to
      ciprofloxacin for treating cholera in children.

PMID- 19578230
TI  - Effect of albumin administration prior to exchange transfusion in term neonates
      with hyperbilirubinemia--a randomized controlled trial.
AB  - OBJECTIVE: To determine the role of intravenous administration of human albumin
      prior to blood exchange in term neonates for reduction of total serum bilirubin
      (TSB). DESIGN: Randomized controlled trial. SETTING: Neonatal Unit of Nemazee
      Hospital, affiliated with Shiraz University of Medical Sciences, southern Iran.
      PATIENTS: Fifty out-born term neonates with gestation age <37 weeks, birth weight
      <2500 g, otherwise healthy with TSB > or =25 mg/dL requiring blood exchange due
      to intensive phototherapy failure. INTERVENTION: Intervention group (n=25)
      received intravenous human albumin 20% (1 g/kg) one hour before exchange while
      the control group (n=25) underwent a blood exchange. OUTCOME MEASURES: TSB level
      at 6 and 12 hours post-exchange, total duration of phototherapy, need for a
      second exchange transfusion and adverse effects. RESULTS: The mean TSB level in
      albumin-treated group was significantly lower than that in the control group at 6
      and 12 hours post-exchange (P<0.001). Mean duration of phototherapy was
      significantly reduced in the albumin-treated group, compared to that in the
      control group (8.6+/-2.4 vs. 25+/-8.2 hours) (P<0.001). None of the neonates in
      albumin-treated group needed exchange transfusion again and no side effects were
      observed. CONCLUSION: Infusion of 20% albumin (1 g/kg) one hour prior to blood
      exchange can significantly reduce the post-exchange total serum bilirubin and
      duration of phototherapy.

PMID- 19578231
TI  - Validation of CRIB II for prediction of mortality in premature babies.
AB  - OBJECTIVE: Validation of Clinical Risk Index for Babies (CRIB II) score in
      predicting the neonatal mortality in preterm neonates < or = 32 weeks gestational
      age. DESIGN: Prospective cohort study. SETTING: Tertiary care neonatal unit.
      SUBJECTS: 86 consecutively born preterm neonates with gestational age < or = 32
      weeks. METHODS: The five variables related to CRIB II were recorded within the
      first hour of admission for data analysis. The receiver operating characteristics
      (ROC) curve was used to check the accuracy of the mortality prediction. HL
      Goodness of fit test was used to see the discrepancy between observed and
      expected outcomes. RESULTS: A total of 86 neonates (males 59.6% mean birthweight:
      1228 +/- 398 grams; mean gestational age: 28.3 +/- 2.4 weeks) were enrolled in
      the study, of which 17 (19.8%) left hospital against medical advice (LAMA) before
      reaching the study end point. Among 69 neonates completing the study, 24 (34.8%)
      had adverse outcome during hospital stay and 45 (65.2%) had favorable outcome.
      CRIB II correctly predicted adverse outcome in 90.3% (Hosmer Lemeshow goodness of
      fit test P=0.6). Area under curve (AUC) for CRIB II was 0.9032. In intention to
      treat analysis with LAMA cases included as survivors, the mortality prediction
      was 87%. If these were included as having died then mortality prediction was
      83.1%. CONCLUSION: The CRIB II score was found to be a good predictive instrument
      for mortality in preterm infants < or = 32 weeks gestation.

PMID- 19578232
TI  - Antiviral treatment for chronic hepatitis C in illicit drug users: a systematic
      review.
AB  - According to recent World Health Organization data, approximately 170-200 million
      people worldwide are infected with hepatitis C virus (HCV). At present, illicit
      drug users (IDUs) constitute the largest group of individuals infected with HCV
      in industrial countries. Between 50% and 90% of IDUs are estimated to be positive
      for anti-HCV antibodies and most of the new infections occur in IDUs. The aim of
      our review is to focus on tertiary prevention of HCV infection among IDUs. We
      review strategies to prevent HCV infection and disease progression, attitude to
      antiviral treatment, access to specific HCV therapy and data of efficacy and
      safety of antiviral treatment among IDUs.

PMID- 19578233
TI  - Hypophosphataemia: an easy strategy for diagnosis and treatment in HIV patients.
AB  - Because HIV infection has become a chronic disease, it is crucial that metabolic
      complications secondary to HIV infection or prolonged therapy be diagnosed and
      managed appropriately over time. Therefore the optimal follow-up becomes complex
      and time consuming. Our review aimed to provide physicians in charge of HIV
      infected patients with key data helping them to diagnose and understand
      hypophosphataemia in HIV patients. Hypophosphataemia is frequent and sometimes
      secondary to renal phosphate wasting. It is very rarely a component of a complex
      proximal tubular disorder, such as Fanconi syndrome. When isolated,
      hypophosphataemia is easy to rule out and treat. In rare cases, prolonged
      hypophosphataemia, when related to renal phosphate wasting and tubular
      dysfunction, might have potential consequences on bone outcome, however, more
      studies are needed. HIV infection by itself might be a risk factor for bone
      metabolism abnormalities; antiretroviral drugs might also be involved. Therefore,
      it seems valuable for patients that the minimal screening should be performed
      routinely, in order to prevent long-term disabilities.

PMID- 19578234
TI  - A review of the natural history of chronic hepatitis B in the era of transient
      elastography.
AB  - Understanding the natural history of chronic hepatitis B is important in order to
      predict the prognosis, to stratify the risk of hepatocellular carcinoma and to
      select appropriate candidates for antiviral treatment. Liver fibrosis is the
      pathogenic process that leads to liver cirrhosis. The study of liver fibrosis in
      the past has largely been hampered by the invasive nature of a liver biopsy. Most
      liver biopsy series represent biased populations with more active disease.
      Transient elastography is a reliable and non-invasive measurement of liver
      fibrosis that allows the study of liver fibrosis among patients without clinical
      indication for liver biopsy. Large studies using transient elastography in
      patients with predominantly normal alanine aminotransferase levels have been
      reported recently. The different roles of patient age, hepatitis B virus DNA and
      alanine aminotransferase levels in the risk stratification for advanced liver
      fibrosis have been defined in hepatitis B e antigen-positive and hepatitis B e
      antigen-negative chronic hepatitis B patients. The relationship between metabolic
      syndrome and chronic hepatitis B is also explored. In this review, new insights
      from studies using transient elastography on the natural history of chronic
      hepatitis B with special focus on liver fibrosis will be summarized and
      discussed.

PMID- 19578235
TI  - Virological response at 4 weeks to predict outcome of hepatitis C treatment with
      pegylated interferon and ribavirin.
AB  - BACKGROUND: Viral kinetics during therapy provides information on how to
      individualize treatment. To determine the benefit of assessing positive
      predictive values (PPVs) and negative predictive values (NPVs) of rapid
      virological responses (RVRs) and early virological responses (EVRs), on-treatment
      outcomes in chronic hepatitis C patients were examined. METHODS: A total of 408
      patients (221 treatment-naive) treated with pegylated interferon-alpha2b and
      ribavirin were included. Hepatitis C virus (HCV) RNA was measured at baseline, 4
      weeks and 12 weeks. RVR was defined as undetectable HCV RNA at 4 weeks and EVR as
      >/=2 log(10) decrease in HCV RNA at 12 weeks. The additive value of RVR on
      predicting sustained virological response (SVR) was assessed with receiver
      operating characteristic (ROC) curves. RESULTS: SVR, RVR and EVR were observed in
      46%, 23% and 78% of patients, respectively. PPVs of RVR were 96%, 100% and 100%
      in treatment-naive patients, relapsers and non-responders, respectively. NPVs of
      failure to achieve EVR were 97%, 75% and 91%, in treatment-naive patients,
      relapsers and non-responders, respectively. At 4 weeks, patients with RVR had the
      highest probability to achieve SVR (odds ratio 44.98 in the entire population and
      32.95 in treatment-naive patients). ROC curves showed the area under the ROC
      curve to be 0.758 versus 0.832 in the entire population and 0.795 versus 0.858 in
      treatment-naive patients at baseline versus week 4, respectively. CONCLUSIONS:
      RVR is a strong predictor of SVR (PPV>96%) and failure to achieve EVR is a strong
      predictor of non-SVR (NPV>75%), independent of patients' pretreatment status.
      Added to baseline characteristics, RVR increased the accuracy to predict SVR. The
      combination of RVR and EVR provided complementary information, and thus provides
      a key opportunity to individualize treatment and improve the benefit/risk ratio
      of therapy.

PMID- 19578236
TI  - Immunological and mutagenic actions of ribavirin monotherapy preceding
      combination therapy with interferon for patients with chronic hepatitis C.
AB  - BACKGROUND: We aimed to investigate the effects of ribavirin on hepatitis C virus
      (HCV). Immunological and virological effects were analysed in patients undergoing
      treatment with ribavirin monotherapy prior to the initiation of combination
      therapy with interferon-alpha. METHODS: A total of 25 patients with chronic HCV
      infection were enrolled in this study. All patients received ribavirin for 4
      weeks during monotherapy; subsequently, interferon-alpha2b was additionally given
      as combined therapy. Patients were divided into two groups according to
      virological response. A rapid viral responder (RVR) was defined as a patient in
      whom HCV RNA became undetectable within 4 weeks after combination therapy. The
      changes of the T-helper (Th)1/Th2 subset of peripheral blood CD4(+) T-cells,
      serum cytokine levels and the alignment of the interferon sensitivity-determining
      region (ISDR) during ribavirin monotherapy were analysed by flow cytometry,
      ELISAs and sequencing methods. RESULTS: A total of 17 patients were classed as
      RVR. In the RVR group, the mean +/-sd serum alanine aminotransferase levels
      significantly decreased (before treatment 103 +/-92 IU/l and after treatment 57
      +/-46 IU/l; P<0.05) during ribavirin monotherapy. The mean +/-sd Th1/Th2 ratio
      significantly increased (before treatment 13.9 +/-5.1 and after treatment 16.7 +/
      6.2; P<0.05), but did not change in the non-RVR group. The levels of Th2
      cytokines (interleukin-10 and soluble CD30) significantly decreased, especially
      in the RVR group. The mean +/-sd mutation rates of ISDR at the nucleotide level
      increased in the RVR group (before treatment 2.6 +/-0.9 sites/clone and after
      treatment 3.9 +/-1.6 sites/clone; P<0.05), but did not change in the non-RVR
      group. CONCLUSIONS: Ribavirin administration might increase the efficacy of
      interferon therapy for patients with chronic hepatitis C by stimulating the host
      immune system and promoting HCV gene mutation.

PMID- 19578237
TI  - HIV type-1 clade C resistance genotypes in treatment-naive patients and after
      first virological failure in a large community antiretroviral therapy programme.
AB  - BACKGROUND: This study aimed to evaluate HIV type-1 (HIV-1) drug resistance
      pretreatment and in those failing first-line non-nucleoside reverse transcriptase
      inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. METHODS:
      This was an observational cohort. Genotypic resistance testing was performed on
      treatment-naive individuals and those failing first-line ART (confirmed HIV-1
      RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002-2007).
      Resistance profiles and mutations relative to timing of known virological failure
      were examined. RESULTS: In total, 230 patients (120 treatment-naive and 110 with
      virological failure) were included: 98% had clade C virus. Among treatment-naive
      patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0
      5.3). Three patients had one significant reverse transcriptase mutation: K65R,
      Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had
      therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C
      (9%). The M184V mutation was the most common mutation, found in 86 (78%)
      patients. In total, 10 (9%) patients had the K65R mutation. More individuals
      tended to develop thymidine analogue mutations when sampling occurred after 6
      months of detected therapy failure (10/31 [32%] individuals) compared with those
      who had genotyping before 6 months (15/79 [19%] patients; P=0.246). CONCLUSIONS:
      Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected
      individuals in South Africa was low during the study period. Patients failing
      first-line ART most often developed resistance to NNRTIs and nucleoside reverse
      transcriptase inhibitors, the two drug classes used in first-line therapy. Viral
      load monitoring in this setting is crucial and individual genotypes in those
      failing first-line therapy should be considered.

PMID- 19578238
TI  - Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)
      infected cells in patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis.
AB  - BACKGROUND: This study was conducted to construct a basis for a therapeutic
      strategy against human T-lymphotropic virus type-I (HTLV-I)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained
      a disulfide moiety, prosultiamine, which is a homologue of allithiamine
      originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I
      infected cells. METHODS: First, we analysed the apoptotic pathway in allicin or
      prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived
      from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated
      the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro
      treatment and in a clinical trial in HAM/TSP patients by quantitative PCR
      analysis of HTLV-I proviral load. RESULTS: Prosultiamine, like allicin, induced
      caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of
      mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1
      cells with prosultiamine treatment suggested that prosultiamine can induce
      caspase-dependent apoptosis through the mitochondrial pathway. On the basis of
      data showing that prosultiamine in vitro treatment against peripheral blood
      CD4(+) T-cells of HAM/TSP patients induced a significant decrease of HTLV-I
      proviral copy numbers by apoptosis of HTLV-I-infected cells, we treated six
      HAM/TSP patients with intravenous administration of prosultiamine for 14 days. As
      a result of this treatment, the copy numbers of HTLV-I provirus in peripheral
      blood decreased to approximately 30-50% of their pretreatment levels with some
      clinical benefits in all patients. CONCLUSIONS: Our results suggest that
      prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I
      infected cells in HAM/TSP.

PMID- 19578239
TI  - The effects of HIV type-1 viral suppression and non-viral factors on quantitative
      proteinuria in the highly active antiretroviral therapy era.
AB  - BACKGROUND: Proteinuria is associated with progressive renal disease and overall
      mortality in HIV-infected patients; however, the prevalence and correlates of
      quantitative proteinuria in the highly active antiretroviral therapy era are
      unknown. METHODS: Spot urine protein to creatinine (P/Cr) ratios, an accepted
      measure of quantitative daily proteinuria, were measured annually since 2002 in
      participants of the AIDS Clinical Trials Group Longitudinal Linked Randomized
      Trials cohort. We used linear regression models with general estimating equations
      to identify factors associated with the abnormal P/Cr thresholds of >/=0.2 and
      >/=1.0. RESULTS: Of the 2,857 participants (most of whom were receiving
      antiretroviral therapy) analysed, 16% and 3% had P/Cr levels >/=0.2 and >/=1.0,
      respectively, at first measurement. P/Cr levels did not change during a median
      follow-up of 3 years (interquartile range 2-4). Factors associated with
      P/Cr>/=0.2 at any measurement included greater age, lower glomerular filtration
      rate, female sex, antiretroviral therapy prior to entry into parent randomized
      trial, HIV type-1 RNA level >/=400 copies/ml, lower CD4(+) T-cell count and
      history of hypertension, diabetes or hepatitis C coinfection (all P<0.04). Black
      race and higher non-high-density lipoprotein cholesterol levels were associated
      with P/Cr levels >/=1.0, but not with P/Cr levels >/=0.2. Hepatitis B coinfection
      and current use of adefovir, indinavir and tenofovir were not associated with
      either of the P/Cr thresholds. CONCLUSIONS: Both HIV-1 and non-HIV-1-related
      factors are associated with abnormal levels of proteinuria and identify those who
      are at a greater risk of worse clinical outcomes. Several of these factors are
      differentially associated with lower and higher proteinuria thresholds.

PMID- 19578240
TI  - HIV type-1 transmission dynamics in recent seroconverters: relationship with
      transmission of drug resistance and viral diversity.
AB  - BACKGROUND: HIV type-1 (HIV-1) has been shown to be frequently transmitted by
      acutely infected patients. We investigated the relationship between the dynamics
      of HIV-1 transmission within recently infected patients, the HIV-1 variability
      and the transmission of antiretroviral drug resistance. METHODS: We included
      patients infected between 1996 and 2006, with a plasma sample obtained <18 months
      after seroconversion and prior to antiretroviral therapy initiation. Reverse
      transcriptase (RT) and protease sequences were determined by direct population
      sequencing from plasma samples. Genotypic resistance was interpreted with the
      Agence Nationale de Recherches sur le SIDA et les Hepatites Virales 2006
      algorithm and International AIDS Society-USA list. Phylogenetic analysis
      (neighbour-joining and maximum likelihood methods) of RT sequences was used to
      determine the HIV-1 subtype and the interrelationship between sequences. RESULTS:
      Genotypic resistance was detected in 37/263 (14.1%) patients. Patients were
      infected by HIV-1 clade B in 222 (84%) cases and with non-B subtypes in 41 (16%).
      A total of 80 (30.4%) RT sequences were segregated in 24 clusters with bootstrap
      values >98% for 22 clusters. The frequency of grouping in clusters was higher
      within B sequences compared with non-B sequences (35.1% versus 4.9%; P<2.10(-4)).
      Drug-resistant isolates were retrieved in only 3 clusters, but the prevalence of
      resistance in clustering viruses (10/80, 12.5%) was not different than in
      isolated sequences. CONCLUSIONS: The segregation into clusters suggested frequent
      forward transmission events in patients infected with HIV-1 subtype B, including
      the possibility of transmission of drug-resistant isolates. These findings
      warrant increasing prevention efforts and serological screening in the at-risk
      populations.

PMID- 19578241
TI  - Adefovir dipivoxil resistance patterns in patients with lamivudine-resistant
      chronic hepatitis B.
AB  - BACKGROUND: Lamivudine (3TC)-resistant chronic hepatitis B patients demonstrated
      a higher rate of adefovir dipivoxil (ADV) resistance compared with nucleoside
      naive patients. This study describes ADV mutation patterns in 3TC-resistant
      patients treated with ADV+3TC or ADV monotherapy, investigating whether mutations
      selected during 3TC therapy predispose to ADV resistance. Risk factors for ADV
      resistance were also evaluated. METHODS: A total of 60 3TC-experienced patients
      were treated with (or switched to) ADV monotherapy (30 patients) or ADV+3TC
      combination therapy (30 patients), and followed for at least 12 months. In all
      patients the hepatitis B virus reverse transcriptase (RT) region was amplified
      and directly sequenced before initiating ADV. The RT sequence was reevaluated for
      virological breakthrough patients and phenotypic analysis was performed for
      several patients. RESULTS: In total, 14 (23%) patients showed virological
      breakthrough (10/30 on ADV monotherapy and 4/30 on ADV+3TC). ADV resistance
      mutations (rtA181V/T and rtN236T) were detected alone or in combination for 11/14
      patients, whereas novel substitutions were present in 3 patients. Before ADV
      treatment, apart from 3TC resistance signature mutations, additional changes were
      found, including the rtA181T mutation, which was already present in 2/14 ADV
      resistant patients. CONCLUSIONS: Although most patients showed virological
      breakthrough because of the well known rtA181V/T and rtN236T substitutions, more
      complex patterns were also found. ADV monotherapy, dose reduction and suboptimal
      virological response after 48 weeks of therapy were significantly associated with
      ADV resistance.

PMID- 19578242
TI  - Incidence rate and risk factors for loss to follow-up in HIV-infected patients
      from five French clinical centres in Northern France - January 1997 to December
      2006.
AB  - BACKGROUND: Our goal was to determine the incidence rate and risk factors for
      loss to follow-up (LTFU) of HIV-infected patients in Northern France. METHODS: We
      estimated the incidence rate of LTFU in 1,007 HIV-infected patients under care
      from January 1997 to December 2006. We then investigated potential risk factors
      for LTFU at inclusion and during follow-up. RESULTS: The incidence of LTFU was
      estimated to be 3.5 per 100 person-years. Risk factors for LTFU at enrolment in a
      multivariate Cox model were age <30 years (hazard ratio [HR] 1.66 versus >40
      years, 95% confidence interval [CI] 1.04-2.64), transmission by injection drug
      use (HR 5.26 versus men who have sex with men, 95% CI 2.90-9.52), no phone number
      provided (HR 5.4, 95% CI 3.6-8.2), no primary care physician (HR 2.10, 95% CI
      1.25-3.52) and sub-Saharan African origin (HR 2.09, 95% CI 1.36-3.22). Patients
      with CD4(+) T-cell counts <200 cells/mm(3) (HR 0.49 versus >/=350 cells/mm(3),
      95% CI 0.32-0.76) and 200-349 cells/mm(3) at baseline (HR 0.63 versus >/=350
      cells/mm(3), 95% CI 0.41-0.98) had a decreased risk of LTFU. During follow-up,
      the risk of LTFU increased when the most recent CD4(+) T-cell count was <200
      cells/mm(3) (HR 2.06, 95% CI 1.16-3.66), the patient was not on highly active
      antiretroviral therapy (HAART; HR 4.20, 95% CI 2.66-6.61) and the patient was on
      HAART but had a detectable viral load (HR 1.92, 95% CI 1.19-3.01). CONCLUSIONS:
      Our findings will help clinicians recognize patients who require additional
      support for retention in care, including younger patients, injection drug users,
      people of sub-Saharan African origin, patients who are healthier at enrolment and
      patients who do not adhere to HAART during follow-up.

PMID- 19578243
TI  - The pattern of pegylated interferon-alpha2b and ribavirin treatment failure in
      cirrhotic patients depends on hepatitis C virus genotype.
AB  - BACKGROUND: Failure of anti-hepatitis C therapy encompasses both primary non
      response and post-treatment relapse. Treatment failure to pegylated interferon
      (PEG-IFN)-alpha2b and ribavirin (RBV) largely depends upon virus genotype, but
      the interaction between genotype, cirrhosis and pattern of treatment failure is
      unclear. We aimed to assess whether cirrhosis modifies the pattern of PEG-IFN
      alpha2b and RBV treatment failure. METHODS: A total of 471 treatment-naive
      patients with histologically proven chronic hepatitis C virus (HCV) infection
      (106 with cirrhosis; 185 with HCV genotype 1 [HCV-1], 157 with HCV genotype 2
      [HCV-2], 92 with HCV genotype 3 [HCV-3] and 37 with HCV genotype 4 [HCV-4]) were
      consecutively treated with PEG-IFN-alpha2b 1.5 microg weekly and weight-based
      RBV. RESULTS: The sustained virological response (SVR) rates were 31% in HCV-1
      and HCV-4, 80% in HCV-2 and 72% in HCV-3, and were lower in cirrhotic than in non
      cirrhotic HCV-1 and HCV-4 (17% versus 36%; P=0.01), and HCV-3 (33% versus 79%;
      P=0.001), but not HCV-2 (69% versus 83%; P=0.1) patients. Treatment failure was
      the consequence of lower end-of-treatment response rates (37% versus 53%; P=0.06)
      plus higher post-treatment relapse rates (55% versus 31%; P=0.07) in cirrhotic
      HCV-1 and HCV-4 patients and higher rates of post-treatment relapse in HCV-2 (29%
      versus 10%; P=0.01) and HCV-3 cirrhotic patients (61% versus 12%; P<0.001). By
      multivariate analysis, HCV-1 and HCV-4 (odds ratio [OR] 7.44, 95% confidence
      interval [CI] 4.87-11.36), and cirrhosis (OR 3.00, 95% CI 1.80-5.00) were
      independent predictors of treatment failure. CONCLUSIONS: Cirrhosis is an
      important moderator of SVR, accounting for different patterns of treatment
      failure in patients infected with different genotypes.

PMID- 19578244
TI  - Clinical and virological responses to clevudine therapy in chronic hepatitis B
      patients: results at 1 year of an open-labelled prospective study.
AB  - BACKGROUND: A previous clinical study of oral clevudine monotherapy for 24 weeks
      demonstrated that it has potent sustained antiviral effects without inducing drug
      resistance. The aim of this study was to evaluate the antiviral effects and
      safety of clevudine monotherapy for 12 months. METHODS: In this open-labelled
      prospective study, 45 treatment-naive chronic hepatitis B patients treated with
      30 mg clevudine once daily for 12 months were monitored at baseline and at 3
      month intervals during treatment. RESULTS: At baseline, the mean age of patients
      was 42 years, 32 were hepatitis B e antigen (HBeAg)-positive and 15 had liver
      cirrhosis. After 12 months of clevudine therapy, the mean serum hepatitis B virus
      (HBV) DNA level in HBeAg-positive patients had decreased by 4.6 log(10) IU/ml.
      Serum HBV DNA was undetectable in 68.7% of patients. HBeAg loss or seroconversion
      was observed in five patients (15.6%) and serum alanine aminotransferase (ALT)
      level had normalized after 12 months of treatment in 75% of patients. In all 13
      HBeAg-negative patients, serum HBV DNA level was undetectable after 12 months of
      therapy and ALT level was normal in 61.5% of patients. Viral breakthrough
      occurred in one patient after 9 months of clevudine treatment. This patient had
      an HBV polymerase mutation, rtM204I. There were no serious adverse events.
      CONCLUSIONS: One-year clevudine therapy is effective for suppressing serum HBV
      DNA level and for normalization of ALT level. Viral breakthrough associated with
      the rtM204I mutation in the HBV polymerase gene occurs during long-term clevudine
      treatment.

PMID- 19578245
TI  - Rapid decrease of wild-type hepatitis C virus on telaprevir treatment.
AB  - BACKGROUND: Telaprevir (TVR) is a hepatitis C virus (HCV) NS3.4A protease
      inhibitor that has exhibited antiviral activity in patients with HCV genotype 1
      infection. The viral dynamics in patients dosed with TVR were compared with those
      reported for patients treated with interferon (IFN). METHODS: The dynamics of
      wild-type HCV genotype 1 in patients dosed with TVR monotherapy (n=36) and TVR
      plus pegylated interferon (PEG-IFN)-alpha2a (n=8) were quantified using a
      biphasic viral dynamic model. RESULTS: Patients dosed with either TVR monotherapy
      or TVR plus PEG-IFN-alpha2a had median first and second phase decreases of 12 per
      day and 1.1 per day, respectively. The second phase decrease was approximately 10
      fold higher than reported values for IFN-based treatments (P<0.0001). Patients
      dosed with TVR plus PEG-IFN-alpha2a had a median remaining viral production after
      blockage (1-epsilon) of -2.37 log(10). In patients dosed with TVR monotherapy,
      increased TVR dosage of the same schedule was related to better blockage.
      CONCLUSIONS: These results suggested that TVR-based regimens for chronic HCV
      infection will lead to an early and more rapid viral decrease that could
      potentially result in higher sustained viral response rates as well as offer the
      potential for a reduced duration of treatment.

PMID- 19578246
TI  - In vivo selection by enfuvirtide of HIV type-1 env quasispecies with optimal
      potential for phenotypic expression of HR1 mutations.
AB  - BACKGROUND: HIV type-1 (HIV-1) resistance to enfuvirtide (ENF) is mediated by
      mutations in the HR1 domain of gp41. We have previously shown that some of these
      mutations are selected in the context of env backgrounds that are not dominant
      before exposure to ENF, suggesting that particular env environments could
      facilitate phenotypic expression of HR1-mediated ENF resistance. METHODS:
      Envelope clones, representing the viral quasi-species present in the longitudinal
      follow-up of a patient who failed ENF-based salvage therapy, were tested for ENF
      susceptibility and Env-related replicative capacity. ENF resistance mutations in
      HR1 were introduced or back-mutated in representative clones to evaluate their
      phenotypic effect in different genetic contexts. RESULTS: The ENF resistance
      levels produced by the introduction of mutation V38A in pretherapeutic env
      sequences were significantly lower than those of env clones harvested after viral
      escape, and in which V38A was naturally selected. Back-mutation of V38A from
      these clones resulted in a strong loss in ENF resistance, but these clones
      retained significant residual resistance, again strongly suggesting the role of
      determinants outside of HR1 in HIV-1 resistance to ENF. By contrast with changes
      in resistance, addition or removal of HR1 mutations in env clones had little
      effect on viral replicative capacity. CONCLUSIONS: The development of ENF
      resistance in vivo is a concerted coevolutionary process whereby HR1 mutations
      are selected within env variants that permit their optimal phenotypic expression.

PMID- 19578247
TI  - Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir
      treatment in HIV-1-infected children.
AB  - BACKGROUND: Once-daily lopinavir/ritonavir (LPV/r) is not approved for treatment
      of HIV paediatric patients. Once daily treatment in children might serve the same
      goals of patient comfort and adherence as in adults. METHODS: HIV type-1-infected
      children aged 6 months to 18 years, who were virologically suppressed on an LPV/r
      containing regimen, were eligible. Treatment 1 consisted of once-daily LPV/r
      460/115 mg/m(2), plus two nucleoside reverse transcriptase inhibitors (NRTIs).
      Treatment 2 consisted of twice-daily LPV/r 230/57.5 mg/m(2) plus two NRTIs.
      Patients were randomized either to start with treatment 1 followed by treatment 2
      or vice versa. Full pharmacokinetic profiles were analysed for lopinavir and
      ritonavir with a validated HPLC tandem mass spectrometry assay. RESULTS: Seven
      patients (five girls and two boys) were included in the study. Median age was 9.8
      years (range 5.8-15.5). For the once-daily treatment, the median (range)
      lopinavir 24 h area under the plasma -concentration-time curve (AUC(24 h)),
      maximum plasma concentration (C(max)) and 24 h plasma concentration (C(24 h))
      were 214.6 h*mg/l (114.2-289.2), 13.5 mg/l (8.3-17.5) and 3.4 mg/l (0.6-7.4),
      respectively. For the twice-daily treatment the median (range) lopinavir 12 h
      area under the plasma concentration-time curve (AUC(12 h)), C(max) and 12 h
      plasma concentration (C(12 h)) were 80.9 h*mg/l (23.3-135.9), 9.8 mg/l (3.4-15.2)
      and 5.7 mg/l (1.7-9.7), respectively. CONCLUSIONS: This study suggests that the
      pharmacokinetics of lopinavir after twice-daily and once-daily dosing are
      similar, with no observable difference in tolerability, in this group of patients
      between 5 and 15 years old.

PMID- 19578248
TI  - Dipotassium trimanganese(II) tetrakis(hydrogenphosphite), K2[Mn3(HPO3)4].
AB  - The title compound is a new mixed alkali/3d metal phosphite. It exhibits a
      layered structure formed by linear Mn(3)O(12) trimer units which contain face
      sharing MnO(6) octahedra interconnected by (HPO(3))(2-) phosphite oxoanions. The
      K(+) cations located between the anionic [Mn(3)(HPO(3))(4)](2-) sheets are
      ninefold coordinated. The presence of the alkaline ion leads to the highest
      symmetry and shortest interlayer distance compared with two previous compounds
      showing the same anionic framework and having ammonium salts as cations. The
      compound crystallizes in the space group R3m, with two crystallographically
      independent Mn atoms occupying sites of 3m and 3m symmetry. All the other atoms,
      except for the phosphite O atoms, are located on special positions with 3m
      symmetry.

PMID- 19578249
TI  - The first three-dimensional vanadium hypophosphite.
AB  - The title synthesized hypophosphite has the formula V(H(2)PO(2))(3). Its
      structure is based on VO(6) octahedra and (H(2)PO(2))(-) pseudo-tetrahedra. The
      asymmetric unit contains two crystallographically distinct V atoms and six
      independent (H(2)PO(2))(-) groups. The connection of the polyhedra generates
      [VPO(6)H(2)](6-) chains extended along a, b and c, leading to the first three
      dimensional network of an anhydrous transition metal hypophosphite.

PMID- 19578250
TI  - Dicopper(II) trihydroxide cyanoureate dihydrate.
AB  - The title compound, poly[[mu-cyanoureato-tri-mu-hydroxido-dicopper(II)]
      dihydrate], {[Cu(2)(C(2)H(2)N(3)O)(OH)(3)].2H(2)O}(n), is a new layered
      copper(II) hydroxide salt (LHS) with cyanoureate ions and water molecules in the
      interlayer space. The three distinct copper(II) ions have distorted octahedral
      geometry: one Cu (symmetry 1) is coordinated to six hydroxide groups (4OH + 2OH),
      whilst the other two Cu atoms (symmetries 1 and 1) are coordinated to four
      hydroxides and two N atoms from nitrile groups of the cyanoureate ions (4OH +
      2N). The structure is held together by hydrogen-bonding interactions between the
      terminal -NH(2) groups and the central cyanamide N atoms of organic anions
      associated with neighbouring layers.

PMID- 19578251
TI  - The centrosymmetric metal metaborate KCdB3O6.
AB  - The title compound, potassium cadmium metaborate, crystallizes in a monoclinic
      cell, featuring infinite one-dimensional CdO(5) chains and trigonal planar B
      atoms in hexagonal B(3)O(6) metaborate ions. The trigonal bipyramidal CdO(5)
      chains and metaborate ions are interlinked to form a three-dimensional framework,
      creating channels running parallel to the [101] direction in which the potassium
      ions reside.

PMID- 19578252
TI  - catena-Poly[[[aqua(ethylenediamine-kappa2N,N')(nitrato-kappaO)copper(II)]-mu-4,4'
      dithiodipyridine-kappa2N:N'] nitrate monohydrate].
AB  - The title compound,
      {[Cu(NO(3))(C(2)H(4)N(2))(C(10)H(8)N(2)S(2))(H(2)O)]NO(3).H(2)O}(n), is composed
      of a one-dimensional linear coordination polymer involving cis-protected
      copper(II) ions and a 4,4'-dithiodipyridine bridging ligand. The polymeric chains
      run along the c-axis direction. N-H...O and O-H...O hydrogen bonds involving the
      coordinating amine groups, nitrate ions and water molecules, as well as
      cocrystallized noncoordinating nitrate ions and water molecules, generate a three
      dimensional structure.

PMID- 19578253
TI  - Di-mu-chlorido-bis[chlorido(4'-p-tolyl-2,2':6',2''-terpyridine
      kappa3N,N',N'')nickel(II)]: a supramolecular system constructed by C-H...Cl
      interactions.
AB  - The title complex, [Ni(2)Cl(4)(C(22)H(17)N(3))(2)], was synthesized
      solvothermally. The molecule is a centrosymmetric dimer with the unique Ni(II)
      centre in a distorted octahedral N(3)Cl(3) coordination environment. The chloride
      bridges are highly asymmetric. In the 4'-p-tolyl-2,2':6',2''-terpyridine ligand,
      the p-tolyl group is perfectly coplanar with the attached pyridine ring, and this
      differs from the situation found in previously reported compounds; however, there
      are no pi-pi interactions between the ligands. The terminal Cl atom forms four
      intermolecular C-H...Cl hydrogen bonds with one methyl and three methine groups.
      The methyl group also forms intermolecular C-H...pi interactions with a pyridine
      ring. These nonclassical hydrogen bonds extend the molecule into a three
      dimensional network.

PMID- 19578254
TI  - Two polymeric structures with a benzene-1,2,4,5-tetracarboxylate ligand acting in
      mu2- and mu4-bridging modes.
AB  - catena-Poly[[tetraaquabis(1H-pyrazole-kappaN(2))nickel(II)] [[diaquabis(1H
      pyrazole-kappaN(2))nickel(II)]-mu-benzene-1,2,4,5-tetracarboxylato
      kappa(2)O(1):O(4)] tetrahydrate],
      {[Ni(C(3)H(4)N(2))(2)(H(2)O)(4)][Ni(C(10)H(2)O(8))(C(3)H(4)N(2))(2)(H(2)O)(2)].4H
      2)O}(n), (I), and poly[[(mu(4)-benzene-1,2,4,5-tetracarboxylato
      kappa(4)O(1):O(2):O(4):O(5))octakis(1H-pyrazole-kappaN(2))dicobalt(II)]
      tetrahydrate], {[Co(2)(C(10)H(2)O(8))(C(3)H(4)N(2))(8)].4H(2)O}(n), (II), are
      polymeric compounds crystallizing in the space group P1, with two independent
      metallic cations and one benzene-1,2,4,5-tetracarboxylate (btc) anion, each lying
      on symmetry centres. Individual coordination polyhedra are regular and the main
      differences are in the way the btc anion binds [mu(2) in (I) and mu(4) in (II)],
      promoting a 'chain-like' one-dimensional structure in (I) and a 'sieve-like' two
      dimensional motif in (II).

PMID- 19578255
TI  - Two different one-dimensional structural motifs in [catena
      {Cu(tacn)}2Pd(CN)4]Br2.[catena-Cu(tacn)Pd(CN)4]2.H2O (tacn is 1,4,7
      triazacyclononane).
AB  - The title compound, catena-poly[[bis[(triazacyclononane
      kappa(3)N,N',N'')copper(II)]-di-mu-cyanido-kappa(4)N:C-palladate(II)-di-mu
      cyanido-kappa(4)C:N] dibromide bis[[(triazacyclononane
      kappa(3)N,N',N'')copper(II)]-mu-cyanido-kappa(2)N:C-[dicyanidopalladate(II)]-mu
      cyanido-kappa(2)C:N] monohydrate],
      {[Cu(2)Pd(CN)(4)(C(6)H(15)N(3))(2)]Br(2).[Cu(2)Pd(2)(CN)(8)(C(6)H(15)N(3))(2)].H(
      )O}(n), (I), was isolated from an aqueous solution containing tacn.3HBr (tacn is
      1,4,7-triazacyclononane), Cu(2+) and tetracyanidopalladate(2-) anions. The
      crystal structure of (I) is essentially ionic and built up of 2,2-electroneutral
      chains, viz. [Cu(tacn)(NC)-Pd(CN)(2)-(CN)-], positively charged 2,4-ribbons
      exhibiting the composition {[Cu(tacn)(NC)(2)-Pd(CN)(2)-Cu(tacn)](2n+)}(n),
      bromide anions and one disordered water molecule of crystallization. The O atom
      of the water molecule occupies two unique crystallographic positions, one on a
      centre of symmetry, which is half occupied, and the other in a general position
      with one-quarter occupancy. One of the tacn ligands also exhibits disorder. The
      formation of two different types of one-dimensional structural motif within the
      same structure is a unique feature of this compound.

PMID- 19578256
TI  - Two polymeric nickel(II) complexes with aromatic benzene-1,2,4,5-tetracarboxylate
      and pyridine-2,5-dicarboxylate linkers.
AB  - (Mu-benzene-1,2,4,5-tetracarboxylato-kappa(2)O(1):O(4))bis[aquabis(2,2
      methylpropane-1,3-diamine-kappa(2)N,N')nickel(II)] methanol disolvate
      tetrahydrate, [Ni(2)(C(10)H(2)O(8))(C(5)H(14)N(2))(4)(H(2)O)(2)].2CH(4)O.4H(2)O,
      (I), is dinuclear, with elemental units built up around an inversion centre
      halving the benzene-1,2,4,5-tetracarboxylate (btc) anion, which bridges two
      symmetry-related Ni(II) cations. The octahedral Ni polyhedron is completed by two
      chelating 2,2-methylpropane-1,3-diamine (dmpda) groups and a terminal aqua
      ligand. Two methanol and four water solvent molecules are involved in a number of
      N-H...O and O-H...O hydrogen bonds which define a strongly bound two-dimensional
      supramolecular structure. The structure of catena-poly[[[bis(2,2-methylpropane
      1,3-diamine-kappa(2)N,N')nickel(II)]-mu-pyridine-2,5-dicarboxylato
      kappa(3)O(5):N,O(2)-[(2,2-methylpropane-1,3-diamine-kappa(2)N,N')nickel(II)]-mu
      pyridine-2,5-dicarboxylato-kappa(3)N,O(2):O(5)] octahydrate],
      {[Ni(2)(C(7)H(3)NO(4))(2)(C(5)H(14)N(2))(3)].8H(2)O}(n), (II), is polymeric,
      forming twisted chains around three independent Ni centres, two of which lie on
      inversion centres and the third in a general position. There are three chelating
      dmpda ligands (one disordered over two equally populated positions), which are
      each attached to a different cation, and two pyridine-2,5-dicarboxylate (pdc)
      anions, both chelating the Ni centre in general positions through an -O-C-C-N-
      loop, while acting as bridges to the remaining two centrosymmetric Ni atoms.
      There are, in addition, eight noncoordinated water molecules in the structure,
      some of which are disordered.

PMID- 19578257
TI  - Two 18e Ti(IV) eta5-Cp-tris(sec-amido)-type complexes derived from 1H-imidazol-2
      yl side-chain functionalized cyclopentadienes.
AB  - Achiral {2-[2-(eta(5)-cyclopentadienyl)-2-methylpropyl]-1H-imidazolyl
      kappaN(1)}bis(N,N-diethylamido-kappaN)titanium(IV),
      [Ti(C(4)H(10)N)(2)(C(12)H(14)N(2))], (I), and closely related racemic (SR)-{2
      [(eta(5)-cyclopentadienyl)(phenyl)methyl]-1H-imidazolyl-kappaN(1)}bis(N,N
      diethylamido-kappaN)titanium(IV), [Ti(C(4)H(10)N)(2)(C(15)H(12)N(2))], (II), have
      been prepared by direct reactions of Ti(NEt(2))(4) and the corresponding 1H
      imidazol-2-yl side-chain functionalized cyclopentadienes. In compound (II), there
      are two crystallographically independent molecules of very similar geometries
      connected by a noncrystallographic pseudosymmetry operation akin to a 2(1) screw
      axis. All Ti-ligating N atoms in both (I) and (II) are in planar environments,
      which is indicative of an additional N-->Ti ppi-dpi donation. This fact and the
      18e nature of both (I) and (II) are additionally supported by quantum chemical
      single-point density functional theory (DFT) computations.

PMID- 19578258
TI  - Bis(di-2-pyridylamine-kappa2N2,N2')(nitrato-kappa2O,O')nickel(II) nitrate.
AB  - In the ionic title compound, [Ni(NO(3))(C(10)H(9)N(3))(2)]NO(3), the central
      Ni(II) atom exhibits cis-NiN(4)O(2) octahedral coordination with three chelating
      ligands, viz. one nitrate anion and two di-2-pyridylamine (dpya) molecules. A
      second nitrate group acts as a counter-ion. The complex cations and the nitrate
      anions are also linked by N-H...O hydrogen bonds. The compound was prepared in
      two different reproducible ways: direct synthesis from Ni(NO(3))(2) and dpya
      yielded systematically twinned crystals (the twinning law is discussed), while
      single crystals were obtained unexpectedly from the Ni(NO(3))(2)/dpya/maleic
      acid/NaOH system.

PMID- 19578259
TI  - Different intermolecular interactions in azido[2-(diphenylphosphino)benzaldehyde
      semicarbazonato-kappa2P,N1,O]nickel(II).
AB  - The title compound, [Ni(C(20)H(17)N(3)OP)(N(3))], is the first complex with a
      semicarbazide-based ligand having a P atom as one of the donors. The influence of
      the P atom on the deformation of the coordination geometry of the Ni(II) ion is
      evident but less expressed than in the cases of complexes with analogous seleno-
      and thiosemicarbazide ligands. The torsion angles involving the two bonds formed
      by the P atom within the six-membered chelate ring have the largest values [C-P
      Ni-N = 24.3 (2) degrees and C-C-P-Ni = -24.2 (4) degrees ], suggesting that the P
      atom considerably influences the conformation of the ring. Two types of N-H...N
      hydrogen bond connect the complex units into chains.

PMID- 19578260
TI  - Poly[[diaqua(mu3-2,2-dimethylmalonato)cadmium(II)] tetrahydrate].
AB  - In the title complex, {[Cd(C(5)H(6)O(4))(H(2)O)(2)].4H(2)O}(n), the
      dimethylmalonate-cadmium metal-organic framework co-exists with an extended
      structure of water molecules, which resembles a sodalite-type framework. In the
      asymmetric unit, there are five independent solvent water molecules, two of which
      are in special positions. The Cd atoms are eight-coordinated in a distorted
      square-antiprismatic geometry by six O atoms of three different dimethylmalonate
      groups and by two water molecules, and form a two-dimensional honeycomb layer
      parallel to the bc plane. Two such layers sandwich the hydrogen-bonded water
      layer, which has a sodalite-type structure with truncated sodalite units composed
      of coordinated and solvent water molecules. This work is the first example of a
      dimethylmalonate cadmium complex containing truncated sodalite-type water
      clusters.

PMID- 19578261
TI  - Trinitratobis{N'-[1-(2-pyridyl)ethylidene]isonicotinohydrazide}cerium(III): a
      three-dimensional cerium-organic supramolecular structure.
AB  - The Ce(III) ion in the title complex, [Ce(NO(3))(3)(C(13)H(12)N(4)O)(2)], is 12
      coordinated by six chelating nitrate O atoms and six donors (2 O and 4 N atoms)
      of two N'-[1-(2-pyridyl)ethylidene]isonicotinohydrazide ligands, exhibiting a
      bicapped pentagonal-antiprism-type coordination geometry. The title complex
      possesses C(2) point symmetry and is located on a twofold crystallographic axis.
      Each molecule is linked with four surrounding molecules by four N-H...N hydrogen
      bonds, resulting in an extended two-dimensional layer parallel to the ab plane,
      while pi-pi interactions between pyridine rings from neighboring complex
      molecules connect the two-dimensional layers into a three-dimensional cerium
      organic supramolecular structure.

PMID- 19578262
TI  - 1,2,3-Trimethoxy-4-[(E)-2-phenylvinyl]benzene and (E,E)-1,4-bis(2,3,4
      trimethoxyphenyl)buta-1,3-diene.
AB  - The stilbene derivative 1,2,3-trimethoxy-4-[(E)-2-phenylvinyl]benzene,
      C(17)H(18)O(3), (I), and its homocoupling co-product (E,E)-1,4-bis(2,3,4
      trimethoxyphenyl)buta-1,3-diene, C(22)H(26)O(6), (II), both have double bonds in
      trans conformations in their conjugated linkages. In the structure of stilbene
      (I), the aromatic rings deviate significantly from coplanarity, in contrast with
      coproduct (II), the core of which is rigorously planar. The deviation in stilbene
      (I) seems to be driven by intermolecular electrostatic interactions. Diene (II)
      sits on a crystallographic inversion centre, which bisects the conjugated
      linkage.

PMID- 19578263
TI  - Structural effects on the solid-state photodimerization of 2-pyridone derivatives
      in inclusion compounds.
AB  - The structures of six crystalline inclusion compounds between various host
      molecules and three guest molecules based on the 2-pyridone skeleton are
      described. The six compounds are 1,1'-biphenyl-2,2'-dicarboxylic acid-2-pyridone
      (1/2), C(14)H(10)O(4).2C(5)H(5)NO, (I-a), 1,1'-biphenyl-2,2'-dicarboxylic acid-4
      methyl-2-pyridone (1/2), C(14)H(10)O(4).2C(6)H(7)NO, (I-c), 1,1'-biphenyl-2,2'
      dicarboxylic acid-6-methyl-2-pyridone (1/2), C(14)H(10)O(4).2C(6)H(7)NO, (I-d),
      1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol-1-methyl-2-pyridone (1/2),
      C(30)H(22)O(2).2C(6)H(7)NO, (II-b), 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol-4
      methy-2-pyridone (1/2), C(30)H(22)O(2).2C(6)H(7)NO, (II-c), and 4,4',4''-(ethane
      1,1,1-triyl)triphenol-6-methyl-2-pyridone-water (1/3/1),
      C(20)H(18)O(3).3C(6)H(7)NO.H(2)O, (III-d). In two of the compounds, (I-a) and (I
      d), the host molecules lie about crystallographic twofold axes. In two other
      compounds, (II-b) and (II-c), the host molecules lie across inversion centers. In
      all cases, the guest molecules are hydrogen bonded to the host molecules through
      O-H...O=C hydrogen bonds [the range of O...O distances is 2.543 (2)-2.843 (2) A.
      The pyridone moieties form dimers through N-H...O=C hydrogen bonds in five of the
      compounds [the range of N...O distances is 2.763 (2)-2.968 (2) A]. In four
      compounds, (I-a), (I-c), (I-d) and (II-c), the molecules are arranged in extended
      zigzag chains formed via host-guest hydrogen bonding. In five of the compounds,
      the guest molecules are arranged in parallel pairs on top of each other, related
      by inversion centers. However, none of these compounds underwent
      photodimerization in the solid state upon irradiation. In one of the crystalline
      compounds, (III-d), the guest molecules are arranged in stacks with one
      disordered molecule. The unsuccessful dimerization is attributed to the large
      interatomic distances between the potentially reactive atoms [the range of
      distances is 4.027 (4)-4.865 (4) A] and to the bad overlap, expressed by the
      lateral shift between the orbitals of these atoms [the range of the shifts from
      perfect overlap is 1.727 (4)-3.324 (4) A]. The bad overlap and large distances
      between potentially photoreactive atoms are attributed to the hydrogen-bonding
      schemes, because the interactions involved in hydrogen bonding are stronger than
      those in pi-pi interactions.

PMID- 19578264
TI  - 2-Methoxy-3-methyl-6-oxo-4-(2,3,4-tri-O-acetyl-beta-D-xylopyranosylamino)-1,6
      dihydropyrimidine-5-carbaldehyde 0.065-hydrate and 2-methylsulfanyl-6-oxo-4
      (2,3,4-tri-O-acetyl-beta-D-xylopyranosylamino)-1,6-dihydropyrimidine-5
      carbaldehyde: hydrogen-bonded structures in one or three dimensions.
AB  - The organic components of 2-methoxy-3-methyl-6-oxo-4-(2,3,4-tri-O-acetyl-beta-D
      xylopyranosylamino)-1,6-dihydropyrimidine-5-carbaldehyde 0.065-hydrate,
      C(18)H(23)N(3)O(10).0.065H(2)O, (I), which crystallizes with Z' = 2 in the space
      group P2(1)2(1)2(1), are linked into a three-dimensional framework structure by a
      combination of four C-H...O hydrogen bonds. In 2-methylsulfanyl-6-oxo-4-(2,3,4
      tri-O-acetyl-beta-D-xylopyranosylamino)-1,6-dihydropyrimidine-5-carbaldehyde,
      C(17)H(21)N(3)O(9)S, (II), where the pyrimidine fragment is disordered with two
      different conformations for the methylsulfanyl substituent, molecules are linked
      into chains of rings by a combination of N-H...O and C-H...O hydrogen bonds.

PMID- 19578265
TI  - Conformational and configurational disorder in 6-(3,4,5-trimethoxyphenyl)-6,7
      dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8(5H)-one and 6-(1,3-benzodioxol-5-yl)-6,7
      dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8-one: a hydrogen-bonded chain of rings and
      pi-stacked hydrogen-bonded chains.
AB  - In 6-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8(5H)
      one, C(19)H(19)NO(6), (I), the six-membered heterocyclic ring adopts a
      conformation intermediate between envelope and half-chair forms; it is disordered
      over two enantiomeric configurations, with occupancies of 0.879 (3) and 0.121
      (3), leading to positional disorder of the 3,4,5-trimethoxyphenyl unit. In 6-(1,3
      benzodioxol-5-yl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8-one,
      C(17)H(13)NO(5), (II), the molecules are similarly disordered, with occupancies
      of 0.866 (4) and 0.134 (4). The molecules in (I) are linked by one three-centre N
      H...(O)(2) hydrogen bond and one two-centre C-H...O hydrogen bond to form a
      complex chain of rings whose formation is reinforced by two independent aromatic
      pi-pi stacking interactions. In (II), a single N-H...O hydrogen bond links the
      molecules into a simple chain, and pairs of chains are linked by a single
      aromatic pi-pi stacking interaction.

PMID- 19578266
TI  - 'Segmented' crystals solved using synchrotron radiation: (2S,3R,4S,5R)-4-(10,10
      dimethyl-3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.0(1,5)]decan-4-ylcarbonyl)
      2,6-diphenylperhydropyrrolo[3,4-c]pyrrole-1,3-dione.
AB  - The title compound, C(29)H(31)N(3)O(5)S, forms needle-shaped ;segmented'
      crystals, thereby inhibiting successful single-crystal data collection using
      conventional laboratory facilities. One crystallite of dimensions 0.15 x 0.03 x
      0.01 mm yielded sufficent single-crystal diffraction data on the Australian
      Synchrotron PX1 beamline. The two independent molecules in the asymmetric unit
      are nearly superimposable and show only minor conformational deviations from
      closely related compounds. The molecules pack using one N-H...O hydrogen bond and
      several phenyl C-H...O(=S), phenyl C-H...O(=C) and methylene C-H...O(=C) hydrogen
      bonds and weak C-H...pi interactions.

PMID- 19578267
TI  - Dipolar S=O...C=O and C-H...O interactions in the molecular organization of 4,6
      di-O-acetyl-2-O-tosyl-myo-inositol 1,3,5-orthoesters.
AB  - In the absence of conventional hydrogen bonding, the molecules of 4,6-di-O-acetyl
      2-O-tosyl-myo-inositol 1,3,5-orthoformate, C(18)H(20)O(10)S, (I), and 4,6-di-O
      acetyl-2-O-tosyl-myo-inositol 1,3,5-orthobenzoate, C(24)H(24)O(10)S, (II), are
      associated via C-H...O interactions. Molecules of (II) are additionally linked
      via dipolar S=O...C=O contacts. It is interesting to note that the sulfonyl O
      atom involved in the dipolar S=O...C=O contacts does not take part in any other
      interaction, indicating the competitive nature of this contact relative to the
      weak hydrogen-bonding interactions.

PMID- 19578268
TI  - Hydrogen-bonded network in the trichloroacetate salts of 2-amino-5
      chloropyridinium and 2-methyl-5-nitroanilinium monohydrate.
AB  - In the crystal structures of 2-amino-5-chloropyridinium trichloroacetate,
      C(5)H(6)ClN(2)(+).C(2)Cl(3)O(2)(-), (I), and 2-methyl-5-nitroanilinium
      trichloroacetate monohydrate, C(7)H(9)N(2)O(2)(+).C(2)Cl(3)O(2)(-).H(2)O, (II),
      the protonated planar 2-amino-5-chloropyridinium [in (I)] and 2-methyl-5
      nitroanilinium [in (II)] cations interact with the oppositely charged
      trichloroacetate anions to form hydrogen-bonded one-dimensional chains in (I)
      and, together with water molecules, a three-dimensional network in (II). The
      crystals of (I) exhibit nonlinear optical properties. The second harmonic
      generation efficiency in relation to potassium dihydrogen phosphate is 0.77. This
      work demonstrates the usefulness of trichloroacetic acid in crystal engineering
      for obtaining new materials for nonlinear optics.

PMID- 19578269
TI  - 4-Benzoyl-3,4-dihydro-2H-1,4-benzoxazine-2-carbonitrile: refinement using a
      multipolar atom model.
AB  - The structural model for the title compound, C(16)H(12)N(2)O(2), was refined
      using a multipolar atom model transferred from an experimental electron-density
      database. The refinement showed some improvements of crystallographic statistical
      indices when compared with a conventional spherical neutral-atom refinement. The
      title compound adopts a half-chair conformation. The amide N atom lies almost in
      the plane defined by the three neighbouring C atoms. In the crystal structure,
      molecules are linked by weak intermolecular C-H...O and C-H...pi hydrogen bonds.

PMID- 19578270
TI  - A structural systematic study of four isomers of difluoro-N-(3-pyridyl)benzamide.
AB  - The four isomers 2,4-, (I), 2,5-, (II), 3,4-, (III), and 3,5-difluoro-N-(3
      pyridyl)benzamide, (IV), all with formula C(12)H(8)F(2)N(2)O, display molecular
      similarity, with interplanar angles between the C(6)/C(5)N rings ranging from
      2.94 (11) degrees in (IV) to 4.48 (18) degrees in (I), although the amide group
      is twisted from either plane by 18.0 (2)-27.3 (3) degrees. Compounds (I) and (II)
      are isostructural but are not isomorphous. Intermolecular N-H...O=C interactions
      form one-dimensional C(4) chains along [010]. The only other significant
      interaction is C-H...F. The pyridyl (py) N atom does not participate in hydrogen
      bonding; the closest H...N(py) contact is 2.71 A in (I) and 2.69 A in (II).
      Packing of pairs of one-dimensional chains in a herring-bone fashion occurs via
      pi-stacking interactions. Compounds (III) and (IV) are essentially isomorphous
      (their a and b unit-cell lengths differ by 9%, due mainly to 3,4-F(2) and 3,5
      F(2) substitution patterns in the arene ring) and are quasi-isostructural. In
      (III), benzene rotational disorder is present, with the meta F atom occupying
      both 3- and 5-F positions with site occupancies of 0.809 (4) and 0.191 (4),
      respectively. The N-H...N(py) intermolecular interactions dominate as C(5) chains
      in tandem with C-H...N(py) interactions. C-H...O=C interactions form R(2)(2)(8)
      rings about inversion centres, and there are pi-pi stacks about inversion
      centres, all combining to form a three-dimensional network. By contrast, (IV) has
      no strong hydrogen bonds; the N-H...N(py) interaction is 0.3 A longer than in
      (III). The carbonyl O atom participates only in weak interactions and is
      surrounded in a square-pyramidal contact geometry with two intramolecular and
      three intermolecular C-H...O=C interactions. Compounds (III) and (IV) are
      interesting examples of two isomers with similar unit-cell parameters and gross
      packing but which display quite different intermolecular interactions at the
      primary level due to subtle packing differences at the atom/group/ring level
      arising from differences in the peripheral ring-substitution patterns.

PMID- 19578271
TI  - Three solvates of a bis-mesoionic fluorescent yellow pigment.
AB  - p-Phenylenebis(2-oxo-3-phenyl-1,2-dihydropyrido[1,2-a]pyrimidin-5-ium-4-olate),
      C(34)H(22)N(4)O(4), is a bis-mesoionic yellow pigment that shows fluorescence in
      the solid state. During a polymorph screening, single crystals of three solvates
      were grown and their crystal structures determined. Solvent-free crystals were
      not obtained. A solvate with N-methylpyrrolidone (NMP) and propan-2-ol,
      C(34)H(22)N(4)O(4).2C(5)H(9)NO.C(3)H(8)O, (Ia), and an NMP trisolvate,
      C(34)H(22)N(4)O(4).3C(5)H(9)NO, (Ib), crystallize with pigment molecules on
      inversion centres. The NMP/propan-2-ol mixed solvate (Ia) forms O-H...O hydrogen
      bonds between the different solvent molecules. In both structures, at least one
      of the solvent molecules is disordered. A third solvate structure,
      C(34)H(22)N(4)O(4).0.5C(5)H(9)NO.C(4)H(10)O, (Ic), was obtained by
      crystallization from NMP and butan-1-ol. In this case, there are two symmetry
      independent pigment molecules, both situated on inversion centres. The solvent
      molecules are heavily disordered and their contribution to the scattering was
      suppressed. This solvate displays a channel structure, whereas the other two
      solvates form layer structures.

PMID- 19578272
TI  - A pair of diastereomeric 1:1 salts of (S)- and (R)-2-methylpiperazine with
      (2S,3S)-tartaric acid.
AB  - The structures of diastereomeric pairs consisting of (S)- and (R)-2
      methylpiperazine with (2S,3S)-tartaric acid are both 1:1 salts, namely (S)-2
      methylpiperazinium (2S,3S)-tartrate dihydrate, C(5)H(14)N(2)(2+).C(4)H(4)O(6)(2
      ).2H(2)O, (I), and (R)-2-methylpiperazinium (2S,3S)-tartrate dihydrate,
      C(5)H(14)N(2)(2+).C(4)H(4)O(6)(2-).2H(2)O, (II), which reveal the formation of
      well defined ammonium carboxylate salts linked via strong intermolecular hydrogen
      bonds. Unlike the situation in the more soluble salt (II), the alternating
      columns of tartrate and ammonium ions of the less soluble salt (I) are packed
      neatly in a grid around the a axis, which incorporates water molecules at regular
      intervals. The increased efficiency of packing for (I) is evident in its lower
      'packing coefficient', and the hydrogen-bond contribution is stronger in the more
      soluble salt (II).

PMID- 19578273
TI  - 4-Aminopyridinium 4-aminobenzoate dihydrate and 4-aminopyridinium nicotinate.
AB  - In the title compounds, 4-aminopyridinium 4-aminobenzoate dihydrate,
      C(7)H(6)NO(2)(-).C(5)H(7)N(2)(+).2H(2)O, (I), and 4-aminopyridinium nicotinate,
      C(5)H(7)N(2)(+).C(6)H(4)NO(2)(-), (II), the aromatic N atoms of the 4
      aminopyridinium cations are protonated. In (I), the asymmetric unit is composed
      of two 4-aminopyridinium cations, two 4-aminobenzoate anions and four water
      molecules, and the compound crystallizes in a noncentrosymmetric space group. The
      two sets of independent molecules of (I) are related by a centre of symmetry
      which is not part of the space group. In (I), the protonated pyridinium ring H
      atoms are involved in bifurcated hydrogen bonding with carboxylate O atoms to
      form an R(1)(2)(4) ring motif. The water molecules link the ions to form a two
      dimensional network along the (101) plane. In (II), an intramolecular bifurcated
      hydrogen bond generates an R(1)(2)(4) ring motif and inter-ion hydrogen bonding
      generates an R(4)(2)(16) ring motif. The packing of adduct (II) is consolidated
      via N-H...O and N-H...N hydrogen bonds to form a two-dimensional network along
      the (102) plane.

PMID- 19578274
TI  - Bubble technique for evaluating effective dose of diagnostic X-rays: a
      feasibility study.
AB  - This study examined the feasibility of applying the bubble technique to evaluate
      effective dose for diagnostic X-rays. A BTI-GAMMA bubble detector from Bubble
      Technology Industries was used for gamma detection. A multi-slab acrylic (PMMA)
      phantom was fabricated to quantify the effective dose E based on an ICRP-60
      report. Accordingly, the bubble detectors were evaluated through preliminary
      tests to ascertain both the reproducibility of specific X-ray doses and the
      linearity of multiple X-ray doses. Qualified bubble detectors were then inserted
      into a multi-slab acrylic phantom. The positions of the inserted bubbles closely
      corresponded with the position of represented organs or tissues. The effective
      dose E of X-ray was determined in 12 organ and tissue samples. The bubble
      detector was maintained at either 21.5 degrees C (for abdomen AP) or 22 degrees C
      (for chest PA) to optimize counting, and the assessed effective doses for males
      and females were 66.75 +/- 10.23 microSv and 66.47 +/- 9.89 microSv,
      respectively, for each chest PA X-ray exposure. The abdominal AP X-ray exposure
      doses were 1183.73 +/- 124.29 microSv and 976.70 +/- 120.13 microSv for males and
      females, respectively. Controlling and holding the bubble detector at an optimal
      ambient temperature during X-ray exposure was the most important issue in
      practical application, and the optimal temperature had to be adjusted slightly
      with incident X-ray to effectively suppress the largest bubbles to enable easy
      reading.

PMID- 19578275
TI  - Etiological and biological characteristics of Erysipelothrix rhusiopathiae
      isolated between 1994 and 2001 from pigs with swine erysipelas in Japan.
AB  - We investigated 66 Erysipelothrix rhusiopathiae strains isolated from pigs
      affected with swine erysipelas in Japan from 1994 to 2001 for serotype,
      pathogenicity towards mice, protection in vaccinated mice and antimicrobial
      susceptibility. Most of the isolates (84.8%) were serotype 1 or 2. For the first
      time, strains belonging to serotype 21 were isolated from cases of septicemia.
      Fifty isolates (75.8%) were highly virulent, 12 isolates (18.2%) were weakly
      virulent and 4 isolates were avirulent strains. All the mice vaccinated with the
      Koganei 65-0.15 vaccine strain survived challenge exposure with 50 highly
      virulent isolates. Six isolates (9.1%) grew on TPB-T80 agar containing 0.02% of
      acriflavine, and this was identical to the growth of the vaccine strain. Forty
      seven isolates (71.2%) were resistant to oxytetracycline. The number of strains
      resistant to oxytetracycline among field isolates increased rapidly each year.
      Tylosin-resistant strains were also isolated (6.1%). These results suggest that
      certain characteristics, particularly antimicrobial susceptibility of E.
      rhusiopathiae isolates, change yearly in the field. Therefore, further
      investigation of the characteristics of E. rhusiopathiae field isolates is
      necessary.

PMID- 19578276
TI  - Development of a chromatographic strip assay for detection of porcine antibodies
      to 3ABC non-structural protein of foot-and-mouth disease virus serotype O.
AB  - A chromatographic strip assay was developed for rapid detection of serum
      antibodies to non-structural protein of foot-and-mouth disease virus. The assay
      was based on Escherichia coli-expressed 3ABC non-structural protein and an
      immunochromatographic technique, which shortened the detection time to about one
      hour. The sensitivity of the assay was determined to be 96.8% for infected pigs;
      its specificity was 100% for naive pigs and 98.8% for vaccinated pigs. In the
      experimentally infected pigs, anti-3ABC antibodies were detectable from eight
      days post-infection until the end of the study, 34 days post-infection. The
      performance of this assay was comparable to that of two commercial ELISA kits,
      Ceditest FMDV-NS and UBI FMDV NS EIA, and was better than that of CHEKIT FMD-3ABC
      po. Given its advantages of instant testing and quantitative measurement, this
      assay has potential as a useful tool for rapid on-farm diagnosis of foot-and
      mouth disease.

PMID- 19578277
TI  - Vaccination effects of recombinant chitinase protein from the hard tick
      Haemaphysalis longicornis (Acari: Ixodidae).
AB  - The success of immunological method for the control of ticks depend on the use of
      potential key antigens as tick vaccine candidates. Chitinase is induced by
      ecdysteroids to degrade the older chitin at the time of molting. Previously, we
      cloned a gene encoding 113 kDa protein (CHT1) of Haemaphysalis longicornis, and
      identified the CHT1 as a protein of chitinase (You et al. 2003). In this study,
      the recombinant CHT1 (rCHT1) expressed in Escherichia coli was used to immunize
      mice. The mice were challenge-infested with ticks at different developmental
      stages of the same species. The rCHT1 stimulated a specific protective anti-tick
      immune response in the mice as evidenced by the significant longer feeding
      periods in the larval ticks and significant difference in the egg weights. The
      molting periods in the ticks fed on the rCHT1-immunized mice tended to be longer
      than those of the controls. Nymphal ticks fed on the rCHT1-immunized mice showed
      lower molting rate (76.7%) compared to 96.7% for the control. These results
      demonstrated that the rCHT1-immunized mice sera implicated on molting step,
      suggesting that the rCHT1 might be a useful vaccine candidate antigen for
      biological control of the tick.

PMID- 19578278
TI  - Therapeutic and preventive effects of methotrexate on zymosan-induced arthritis
      in SKG mice.
AB  - The purpose of this study was to investigate the pathology of zymosan-induced
      arthritis in the SKG mouse model of rheumatoid arthritis in humans, and to
      validate this model as a reliable drug screening system. To achieve this purpose,
      methotrexate (1 or 10 mg/kg, once daily) or vehicle only was administered
      intraperitoneally to SKG mice with zymosan-induced arthritis. Histologically,
      this arthritis was characterized by the presence of granulation tissue rich in
      granulocytes. Methotrexate suppressed the development of arthritis in ankle and
      wrist joints in both clinical and histological studies. These results indicated
      that methotrexate has not only prophylactic, but also therapeutic effects on
      zymosan-induced arthritis developed in SKG mice and may thus be a promising
      control agent for drug research in the SKG mouse model of rheumatoid arthritis.

PMID- 19578279
TI  - Expression analysis of early response-related genes in rat liver epithelial cells
      exposed to thioacetamide in vitro.
AB  - Thioacetamide (TA) is a potent hepatotoxicant known to affect liver metabolism,
      inhibit mRNA transport and induce immune suppression. The genetic mechanism
      underlining this biological toxic compound is well understood using microarray
      technology. Thus, we used high-throughput rat genome oligonucleotide microarrays
      containing approximately 22,000 genes to investigate the genetic components of TA
      related cytotoxicity in WB-F344 rat liver epithelial (WB-F344) cells. We treated
      cells with TA (two concentrations over five time periods, ranging from 1 to 24
      hr), isolated total RNA at 1, 3, 6, 12 and 24 hr following TA treatment and
      hybridized the RNA to microarrays. Clustering analysis distinguished two groups
      of genes, early (1 and 3 hr) and late (6, 12 and 24 hr) phase genes. In total,
      2,129 and 2,348 differentially-expressed genes were identified following
      treatment with low and high concentrations of TA, respectively. A common set of
      1,229 genes that were differentially expressed following treatment with both low
      (1,000 muM) and high (10,000 muM) concentrations of TA had similar expression
      patterns. Interestingly, 1,410 genes at the low concentration and 1,858 genes at
      the high concentration were differentially expressed in the early phases,
      suggesting that these genes associated with the early response to TA may be
      useful as early markers of hepatotoxicity.

PMID- 19578281
TI  - Quercetin prevents cardiac hypertrophy induced by pressure overload in rats.
AB  - Inhibition of cardiac hypertrophy leads to a significant reduction in
      cardiovascular mortality and morbidity. Quercetin is by far the most abundant
      flavonoid and believed to ameliorate cardiovascular disease. Therefore, we
      investigated whether quercetin supplementation could attenuate the development of
      cardiac hypertrophy induced by pressure overload. Three weeks after suprarenal
      transverse abdominal aortic constriction, heart to body weight (HW/BW) ratio
      increased compared to the sham group (3.40 +/- 0.06 mg/g versus 2.83 +/- 0.02
      mg/g, P<0.001). The quercetin administered group showed complete inhibition of
      cardiac hypertrophy (2.85 +/- 0.01 mg/g, P<0.001). Malonyldialdehyde production
      induced by pressure overload was suppressed by quercetin. The activities of
      extracellular signal-regulated kinase (ERK1/2), p38 MAP kinase, Akt and GSK-3beta
      were significantly increased with pressure overload and attenuated by quercetin
      treatment. We conclude that quercetin appears to block the development of cardiac
      hypertrophy induced by pressure overload in rats and that these effects may be
      mediated through reduced oxidant status and inhibition of ERK1/2, p38 MAP kinase,
      Akt and GSK-3beta activities.

PMID- 19578280
TI  - Sustained efficacy of erythropoietin with a hydroxyapatite carrier administered
      in mice.
AB  - For chronic kidney disease patients with renal anemia, recombinant human
      erythropoietin (rHuEPO) is a very effective drug; however, the treatment regime
      is troublesome, requiring multiple administrations each week. In the present
      study, we examined the efficiency of hydroxyapatite (HAp) as a drug delivery
      carrier for the sustained release of erythropoietin (EPO) to reduce the frequency
      of administration. Spray-dried HAp microparticles, formed from zinc-containing
      HAp (Zn-HAp) and Zn-HAp calcined at 400 degrees C, were used as carriers of EPO,
      and five Zn-HAp formulation samples incorporating EPO were prepared; no
      formulation, poly-L-lactic acid (PLA) formulation, zinc (Zn) formulation, Zn/PLA
      formulation, and calcined/Zn/PLA formulation. ICR mice were administered these
      samples or commercial rHuEPO (Epogin) as a control from dorsal neck subcutaneous,
      and hematological and histopathological analyses, including enzyme-linked
      immunosorbent assay for plasma EPO concentration, were performed. An increase in
      the blood EPO level was detected on days 3 and 8 post-administration. Peak
      hematopoiesis was delayed and higher hematological values were obtained on day 14
      post-administration with no serious adverse reactions compared with the control.
      The Zn/PLA formulation sample was found to be most effective in reducing the
      initial peak while sustaining the delayed release of EPO. In conclusion, the Zn
      HAp formulation samples were considered to be useful carriers for the sustained
      release of EPO, and the Zn/PLA formulation appears to be the most effective of
      five Zn-HAp formulation samples in sustaining EPO release.

PMID- 19578282
TI  - Histoplanimetrical study on the relationship between cellular kinetics of
      epithelial cells and proliferation of indigenous bacteria in the rat colon.
AB  - The aim of this study was to clarify the regulatory effects of epithelial
      kinetics on indigenous bacterial proliferation in the large intestine. The
      lifespan, migration speed and proliferation rate of crypt epithelial cells in the
      initial 20% of the colon (proximal colon) and the 50% of the colon (middle colon)
      in bromodeoxyuridine-administrated rats were histoplanimetrically and
      chronologically compared. The proximal colon possessed well-developed mucosal
      folds and a large amount of indigenous bacteria which filled the crypt lumen,
      whereas no folds or bacteria were found to occupy the crypt lumen in the middle
      colon. The cell lifespans were 32.2, 42.5 and 33.6 hr in the apical and the basal
      parts of the mucosal folds of the proximal colon, and in the middle colon,
      respectively. The migration speeds were 4.2, 2.1 and 3.3 microm/hr, respectively,
      while the appearance frequencies of proliferating cell nuclear antigen (PCNA)
      positive crypt epithelial cells were 35.0, 24.6 and 33.8%. These findings suggest
      that the lifespan was shortened and the migration speed increased in the most
      luminal mucosa of colon, contributing to the elimination of the adhered bacteria
      from the most luminal mucosa. By contrast, the elongation of the lifespan and
      deceleration of the migration of epithelial cells in the basal parts of the
      mucosal folds might contribute to reliable settlement of indigenous bacteria,
      resulting in the maintenance of a large amount of indigenous bacteria in the
      lumen of the proximal colon.

PMID- 19578283
TI  - Effects of high cholesterol diet on newly generated cells in the dentate gyrus of
      C57BL/6N and C3H/HeN mice.
AB  - In this study, we observed and compared the effects of a high cholesterol diet
      (HCD) on cell proliferation and differentiation in the subgranular zone of the
      dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant
      strain) mice. Ki67 (a marker for cell proliferation) positive cells) were
      significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and
      C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a
      marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed
      B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H
      mice. These results suggest that B6 strains are sensitive to HCD, which impairs
      cell proliferation and differentiation.

PMID- 19578284
TI  - Visualization of the thoracic duct with injections of dyes or contrast media into
      the testicular parenchyma in the rabbit.
AB  - The thoracic duct drains lymph from the caudal part of the body to the venous
      system. The visualization of the thoracic duct is important for diagnosis of
      chylothorax, which may be caused by the damage of the duct. However, it is not
      easy to visualize the thoracic duct by injecting dyes and/or contrast media into
      peripheral lymph nodes and mesenteric lymphatics. In the present study, we
      examined whether the thoracic duct can be visualized by injecting dyes and
      contrast media directly into the testicular parenchyma. Under deep pentobarbital
      anesthesia, 14 male Japanese White rabbits were percutaneously injected with dyes
      (India ink or methylene blue) or contrast media (iohexol 240, 300, or
      Lipiodol(TM)) into the testicular parenchyma. Then, we grossly observed the
      stained thoracic duct or took radiographs and CT images of the duct. In all cases
      with dyes injections, the thoracic duct was successfully visualized. We observed
      stained lymphatic vessels from the testis to the duct. In case of contrast media
      injections, the thoracic duct was visualized with X-ray and CT imaging, when 1.5
      2.0 ml per one testis of iohexol 240 at 37 degrees C were injected into the right
      or both testes. The duct was most clearly visible, 3-5 min after the injections.
      The results show that the thoracic duct is reliably visualized simply by
      injecting dyes or contrast media into the testicular parenchyma. Our
      visualization method may also be applicable to the diagnosis of chylothorax in
      male animals.

PMID- 19578285
TI  - The effects of different anesthetic agents on short electroretinography protocol
      in dogs.
AB  - The purpose of this article was to investigate the effects of sedatives and
      general anesthetics, such as tiletamine-zolazepam, medetomidine, and isoflurane
      on the short ERG protocol. Six healthy mongrel dogs were assessed by a convenient
      short ERG protocol with the owners' consent. The amplitudes of a-wave and b-wave,
      as well as the implicit time of ERG under different anesthesia statuses, were
      recorded and analyzed. The amplitudes of ERG waves were not significantly
      different between tiletamine-zolazepam and medetomidine groups, except in b-wave
      after 5 min dark adaptation (140 +/- 42 microV in tiletamine-zolazepam and 101 +/
      32 microV in medetomidine, p<0.01). The amplitude of ERG recorded in isoflurane
      (5 +/- 3 microV of a-wave and 12 +/- 6 microV of b-wave under light adaptation;
      41 +/- 19 microV of b-wave after 1 min dark adaptation; 28 +/- 15 microV of a
      wave and 58 +/- 32 microV of b-wave after 5 min dark adaptation) were
      significantly different from tiletamine-zolazepam (8 +/- 2 microV of a-wave and
      24 +/- 9 microV of b-wave under light adaptation; 117 +/- 44 microV of b-wave
      after 1 min dark adaptation; 59 +/- 18 microV of a-wave and 140 +/- 42 microV of
      b-wave after 5 min dark adaptation), except in a-wave after 1 min dark adaptation
      (39 +/- 13 microV in tiletamine-zolazepam and 34 +/- 17 microV in isoflurane).
      Comment-General anesthesia had significantly lower amplitudes in the dark-adapted
      group compared with the sedation group. Therefore, tiletamine-zolazepam is a
      desirable choice for the short ERG protocol in dogs.

PMID- 19578286
TI  - Aberrations of the FHIT gene and Fhit protein in canine lymphoma cell lines.
AB  - The fragile histidine triad (FHIT) gene is a tumor-associated gene, and aberrant
      FHIT gene and protein expression have been described in many types of human
      tumors. Furthermore, it has been reported that FHIT gene inactivation is induced
      by hypermethylation of 5' CpG islands in the gene or by genomic deletion around
      the open reading frame (ORF). In this study, we explored the aberrations in the
      canine FHIT gene and Fhit protein expression and assessed the methylation status
      and genomic deletions by using 5 canine lymphoma cell lines. We found that the
      decrease in the expression of the Fhit protein in canine lymphoma cell lines was
      similar to that in human tumors. The expression of the wild-type FHIT transcript
      was reduced in all 5 cell lines. However, we could not confirm the involvement of
      aberrant methylation events in the 5' CpG islands of the canine FHIT gene. We
      were able to identify homozygous or heterozygous deletions in the canine FHIT
      genes in all 5 cell lines. Moreover, a widespread genomic deletion of the FHIT
      gene, which included the ORF region, was detected in 1 cell line. In the present
      study, we detected aberrations in the FHIT gene and Fhit protein expression in
      all 5 canine lymphoma cell lines, and this phenomenon might be an important
      factor in promoting canine lymphoma.

PMID- 19578287
TI  - Scanning electron microscopic observation of ultrastructure of Dirofilaria
      immitis microfilaria.
AB  - Ultrastructure of Dirofilaria immitis microfilaria(Mf) was imaged through
      scanning and transmission electron microscopies. Transverse annular striations
      covered all over the surface of the whole body. Two small pores on the cephalic
      disk and the mouth-like cavity at a ventral side of the first striation next to
      the cephalic disk were observed. A single triangular hook was projected from the
      upper palate. The excretory pore was observed at the 80th annulus from the
      anterior end, and the anal pore at the 90th annulus from the posterior end. The
      both pores were located at the ventral side of the body. This study first
      demonstrated that a large number of nuclear column cells were distributed in the
      body cavity. These cells were spherical and about 1 microm in diameter. Each of
      the cells contained a spherical nucleus and was connected to each other by micro
      strings that were running radially. Many flattened muscle cells were located at
      the inside of the hypodermis of the whole body. The tail contained only a single
      longitudinal muscle cell.

PMID- 19578288
TI  - Cutaneous nocardiosis in a cat.
AB  - A 4-year-old spayed female domestic shorthair cat was presented to us for
      swelling of all foot pads. The skin lesions were histopathologically diagnosed as
      suppurative pyogranulomatous panniculitis. The lesions did not respond to
      cephalexin, prednisolone or itraconazole. However, complete resolution of the
      skin lesions was obtained with doxycycline. A littermate living in the same
      household developed similar skin lesions that were also successfully treated with
      doxycycline. Polymerase chain reaction analysis detected the 16S ribosomal RNA
      gene of Nocardia spp. in DNA extracted from lesion pus, and direct nucleotide
      sequencing analysis revealed 100% homology with Nocardia elegans. We diagnosed
      this case as nocardiosis.

PMID- 19578289
TI  - Gene expression of adrenomedullin in canine normal tissues and diseased hearts.
AB  - The purposes of this study were to determine the tissue distribution of canine
      adrenomedullin (AM) and to determine whether increased canine AM mRNA expression
      is associated with congestive heart failure (CHF) due to mitral regurgitation
      (MR). Canine AM mRNA expression was detectable in various normal tissues,
      including cardiovascular tissues. In addition, the AM mRNA expression in the left
      atrium of dogs with MR was significantly higher than that in normal subjects. In
      conclusion, AM is a potential neurohumoral factor in dogs with CHF due to MR.

PMID- 19578290
TI  - A retrospective survey of the prevalence of complex vertebral malformation
      carriers in 9 Holstein dairy herds in Hokkaido, Japan.
AB  - The carrier rates of Complex Vertebral Malformation (CVM) in 9 Holstein dairy
      herds in Hokkaido, number of usages of CVM carrier semen for breeding and gene
      frequencies of CVM carriers were measured. The mean CVM carrier rates of 140 cows
      from 4 herds in 1994 and 315 cows from 5 herds in 2003 were 10.8%(range 4.7
      30.0%) and 5.1%(range 0.0-6.1%), respectively. The rate of use of CVM carrier
      semen in the Hokkaido district was 5.6% in 2002. The gene frequencies calculated
      from CVM carriers among the 315 cows and number of CVM carrier semen samples used
      were 0.032 and 0.028, and the occurrence of homozygous CVM in 2003 was estimated
      to be 0.1% in the local districts of Hokkaido, Japan.

PMID- 19578291
TI  - Prevalence of Leptospira spp. in the kidneys of wild boars and deer in Japan.
AB  - We surveyed the prevalence of Leptospira spp. from 2005 to 2008 in wild boars and
      deer in Japan using polymerase chain reaction. Leptospiral flaB was detected in
      the kidneys of wild boars (positive ratio, 15.2%; 22 of 145) from 9 prefectures
      and a deer (1.1%; 1 of 94) from 1 prefecture in Japan. There was no annual change
      in the prevalence of positive animals during the investigation period (chi
      squared test, p=0.94) or in the prevalence in male and female wild boars in the
      2007 to 2008 season (Fisher's exact test, P=0.45). The Leptospira species
      harbored by these animals were deduced to be L. interrogans (from 22 animals) and
      L. borgpetersenii (from 1 animal).

PMID- 19578292
TI  - Bovine viral diarrhea virus 2 infection activates the unfolded protein response
      in MDBK cells, leading to apoptosis.
AB  - Bovine viral diarrhea virus 2 (BVDV-2) strains are divided into cytopathic and
      non-cytopathic biotypes based on the ablity to induce cytopathic effects in
      cultured cells. The mechanism of cytopathogenicity of BVDV-2 is not well
      understood. We examined cytopathogenesis in MDBK cells resulting from BVDV-2
      infections by microscopic examinations and microarray analysis. We found that
      BVDV-2 activates endoplasmic reticulum (ER) stress signaling pathways that
      contribute to apoptosis of infected cells. We also monitored the expression of ER
      stress marker gene by RT-PCR during BVDV-2 infection and demonstrated that
      infection of MDBK cells with a cytopathic strain of BVDV-2 induces glucose
      regulated protein 78 expression. Infection with BVDV-2 also induces DNA-damage
      inducible transcript 3 expression and downregulates the lectin-galactoside
      binding soluble 1 level. These results show that cytopathic strains of BVDV-2
      induce an ER stress response resulting in apoptosis.

PMID- 19578293
TI  - Comparison of the alkalizing effects of bicarbonate precursors in calves with
      experimentally induced metabolic acidosis.
AB  - The aims of this study were to confirm whether commercial acetated Ringer's
      solution, which contains 28 mM of sodium acetate, is superior to commercial
      lactated Ringer's solution in alkalizing effects in calves with experimentally
      induced metabolic acidosis. Twenty calves with experimentally induced mild
      acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated
      or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The
      acetated Ringer's solution induced a significantly greater increase in venous
      HCO(3)(-) and base excess concentrations than the other fluids during the early
      phases of extracellular fluid replacement in mild metabolic acidosis. Therefore,
      the alkalizing effect of commercial acetated Ringer's solution is superior to
      commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic
      acidosis in calves.

PMID- 19578294
TI  - Influence of the time between removal and cooling of the canine epididymis on
      post-thaw caudal epididymal sperm quality.
AB  - The effects of the time period between canine epididymis removal and cooling on
      post-thaw caudal epididymal sperm quality were investigated. Sperm recovered from
      the epididymis stored for 6 hr at 4 or 20 degrees C exhibited similar motility.
      However, when the epididymis was stored for 12 hr or longer at 20 degrees C,
      sperm motility was significantly lower than that at 4 degrees C (p<0.01). The
      post-thawed qualities of sperm recovered from the caudal epididymides that had
      been stored at 20 degrees C for 0 or 6 hr and then at 4 degrees C for 24 hr after
      removal were not significantly different. Therefore, leaving the canine
      epididymis at 20 degrees C for up to 6 hr after its removal may have little
      effect on the post-thaw quality of recovered caudal epididymal sperm.

PMID- 19578295
TI  - Disseminated histiocytic sarcoma with excessive hemophagocytosis in a cat.
AB  - A 10-year-old Japanese domestic cat was presented with anorexia and weight loss.
      Severe anemia and thrombocytopenia were detected. Abdominal radiography and
      ultrasonography revealed the presence of multiple masses in the spleen.
      Cytological analyses of the masses revealed several atypical histiocytic cells
      and considerable hemophagocytosis. A splenectomy was performed, and the mass was
      diagnosed as histiocytic sarcoma on the basis of histopathological, cytochemical
      and immunohistochemical analyses. Further, abnormal hemophagocytosis was observed
      in the bone marrow. The cat was administered prednisolone and lomustine, and it
      survived for 107 days after admission. An autopsy revealed the presence of
      neoplastic histiocytic cells in the bone marrow, liver, pancreatic lymph node and
      glomeruli. This is the first case of histiocytic sarcoma in a cat to be reported
      in Japan.

PMID- 19578296
TI  - Dimensions of the foot muscles in the lowland gorilla.
AB  - We dissected the hindlimb of a female western lowland gorilla and determined the
      muscle dimensions (mass, fascicle length, and physiological cross-sectional area:
      PCSA). Comparisons of the muscle parameters of the measured gorilla with
      corresponding reported human data demonstrated that the triceps surae muscles
      were larger and had more capacity to generate force than the other muscle groups
      in both species, but this tendency was more prominent in the human, probably as
      an adaptation to strong toe-off during bipedal walking. On the other hand, PCSAs
      of the extrinsic pedal digital flexors and digiti minimi muscles were larger in
      the western lowland gorilla, suggesting that the foot, particularly the fifth
      toe, has a relatively high grasping capability in the lowland gorilla.

PMID- 19578297
TI  - Rabies immune status of dogs brought into the Hyogo Prefecture Animal Well-being
      Center, Japan.
AB  - Stray dogs are a public health risk factor when canine rabies is endemic. The
      Rabies Prevention Law has introduced measures to control stray dogs, but many
      dogs are still captured in Japan. In order to estimate the immune status of stray
      dogs for the purposes of risk management, we conducted a serological survey at
      the Hyogo Prefecture Animal Well-being Center. Only 27.7% of dogs brought into
      the Center (n=166) had protective immune status. This result suggests that there
      is the potential for reintroduction of canine rabies into stray dogs, leading to
      endemic rabies and its transmission to humans. Continued removal of stray dogs,
      education on rabies prevention and vaccination of dogs therefore remain important
      public health issues.

PMID- 19578298
TI  - Rhabdomyosarcoma with posterior paresis and megaesophagus in a Holstein heifer.
AB  - A 7-month-old Holstein heifer presented with posterior paresis and megaesophagus.
      At post mortem examination, a nodular tumor was found attached to the thoracic
      wall and the eighth to eleventh thoracic vertebrae, adjacent to the left
      posterior pulmonary lobe. The tumor was diagnosed as rhabdomyosarcoma by
      histology. This is a very rare case of spinal infiltration of rhabdomyosarcoma in
      cattle.

PMID- 19578299
TI  - Kaposi-like vascular tumor of the urinary bladder in a cow.
AB  - Kaposiform hemangioendothelioma is a rare human vascular neoplasm. In veterinary
      medicine this tumor type was only recognized in the dog. Here we describe an
      unusual case arising in the urinary bladder of a Holstein-Friesian adult cow.
      Histologically the tumor presented a nodular proliferation of spindle cells,
      forming angular slits, often containing extravasated erythrocytes.
      Peripherically, well-formed vascular channels were seen. These cells were
      positive to vimentin and to factor VIII-related antigen by immunohistochemical
      stain. Based on its characteristics, it was classified as kaposiform
      hemangioendothelioma and as far as we know, it is the first case described in
      cattle.

PMID- 19578300
TI  - A case report: a dog with acute onset of Hepatozoon canis infection.
AB  - We present a clinical overview of a dog with acute onset of Hepatozoon canis
      infection. A stray female beagle dog of unknown age was referred to Kagoshima
      University showing anemia. Blood tests revealed the presence of anemia,
      thrombocytopenia, hyperproteinemia, polyclonal gammopathy, hypoalbuminemia, and
      elevated creatine kinase and alkaline phosphatase activities. In addition,
      capsule-like organisms were detected in the cytoplasm of approximately 50% of
      neutrophils in blood smears. H. canis infection was confirmed by polymerase chain
      reaction and DNA sequencing analyses. Amplified DNA fragments revealed 100%
      identity to the 18S ribosomal RNA gene of H. canis. The clinical symptoms
      improved after the administration of antibiotics. Hepatozoonosis in dogs is rare,
      but veterinarians should be alert to its possible acute onset.

PMID- 19578301
TI  - PCR detection of four virulence-associated genes of Campylobacter jejuni isolates
      from Thai broilers and their abilities of adhesion to and invasion of INT-407
      cells.
AB  - Campylobacter jejuni is a major cause of food borne pathogens in humans and a
      major reservoir for this pathogen is poultry. The C. jejuni in broilers was
      investigated from in the caeca of broilers. Twenty broiler/flock samples from 7
      flocks were assessed. The average prevalence of C. jejuni was 65% in the broiler
      flocks. The adhesion and invasion ability of 48 strains of C. jejuni on INT 407
      were studied. The adhesion and invasion ability of 48 Campylobacter isolates from
      caecal contents were analyzed with Human embryonic intestine (INT-407) cells
      being used as a gentamicin resistance assay. The caecal isolates exhibited a wide
      range of adherence and invasion ability. There was a significant correlation
      (p<0.01) between the adherence and the invasion ability of the Campylobacter
      isolates. Each of the virulence-associated genes: dnaJ, cadF, pldA and ciaB was
      detected by polymerase chain reaction from 100, 76, 31 and 41% of the
      Campylobacter strains, respectively. All of four virulence-associated genes were
      detected in 11 isolates. However, there was unclear association between the
      invasion ability and the presence of virulence-associated genes in this
      experiment, suggesting that more genes may be involved in the invasion process.

PMID- 19578302
TI  - Application of a reservoir-type calcitriol transdermal patch in dairy cattle.
AB  - Our objective was to evaluate the effects of a reservoir-type calcitriol (5
      mg/animal) transdermal patch on plasma calcitriol and calcium (Ca) concentrations
      in dairy cattle. A group of six heifers received three different types of
      patches: an encapsulated reservoir solution containing calcitriol alone (CAL),
      calcitriol with dodecylamine (CAL+D), or vehicle (CONT). The patches were applied
      to the skin of the tail for duration of 2 days at intervals of at least 3 weeks.
      Cattle that received CAL or CAL+D showed significant increases in plasma
      calcitriol and Ca concentrations on day 2 and days 2 and 3, respectively. The
      areas under the plasma concentration-time curve (AUC) values for plasma
      calcitriol and Ca in the CAL and CAL+D groups increased significantly compared to
      the CONT group. The data of this study describe evidence of measurable
      transdermal absorption of exogenous calcitriol from a patch and its sufficient
      biological action to elevate plasma Ca concentrations.

PMID- 19578303
TI  - Slime production and antibiotic resistance of Enterococcus faecalis isolated from
      arthritis in chickens.
AB  - Slime factor production and antibiotic resistance of 67 Enterococcus faecalis
      strains isolated from chicken arthritis were investigated in this study. Slime
      factor productions of enterococci were found as 59.7%. The antibiotic resistances
      were investigated by testing gentamycin, penicillin, streptomycin, vancomycin,
      danofloxacin, and enrofloxacin. The resistance rates were found as 62.68%,
      76.11%, 67.16%, 13.43%, 47.76%, 43.28%, respectively. For slime factor positive
      enterococci, the antibiotic resistance rates were found as follows respectively;
      82.50%, 87.50%, 92.50%, 17.50%, 72.50%, and 60.00%. In conclusion; the slime
      factor might play a role as a colonization factor for chicken arthritis and slime
      factor positive enterococci were found to be more resistant to these antibiotics.
      The resistance rates between slime factor positive and negative enterococci
      against the tested antibiotics except for vancomycin were found statistically
      significant (p<0.05).

PMID- 19578304
TI  - [Natural history and long-term outcome of ulcerative colitis].

PMID- 19578305
TI  - [Current treatment for severe ulcerative colitis].

PMID- 19578306
TI  - [Long-term results after proctocolectomy with ileal pouch-anal anastomosis for
      ulcerative colitis].

PMID- 19578307
TI  - [Pouchitis].

PMID- 19578308
TI  - [Controversy in surveillance for ulcerative colitis].

PMID- 19578309
TI  - [Interface of surgery and internal medicine in the treatment of ulcerative
      colitis: discussion].

PMID- 19578310
TI  - [A case of the oldest old patient with advanced esophageal cancer responding
      completely to the combination chemotherapy of docetaxel/5-fluorouracil/nedaplatin
      with radiation].
AB  - An 86-year-old man was admitted with dysphagia. Endoscopic examination revealed
      an advanced esophageal cancer located in the lower thoracic esophagus.
      Histological analysis revealed moderately differentiated squamous cell carcinoma.
      The clinical stage was diagnosed as T2N0M0, stage II. He received radiation
      therapy in combination with chemotherapy using docetaxel, 5-fluorouracil and
      nedaplatin. After chemoradiotherapy (CRT), the carcinoma could not be detected by
      CT or endoscopy, and endoscopic biopsy revealed no cancer cells in categorization
      as resulting complete response. Adverse event consisted of grade 2 in leukopenia.
      We could not detect relapse, metastases or late side effect of CRT at present, 24
      months after CRT.

PMID- 19578311
TI  - [Isolated spontaneous dissection of the superior mesenteric artery in two cases
      treated with conservative therapy].
AB  - We report two cases of isolated spontaneous dissection of the superior mesenteric
      artery (SMA). Both patients complained of abdominal pain with sudden onset and
      were given diagnoses of dissection of the SMA based on abdominal CT scanning. CT
      showed dissention of the SMA with thrombosis of the false lumen and narrowing of
      the true lumen. Therefore there were no symptoms of bowel ischemia, and after
      hospitalization both cases received conservative therapy with anticoagulation and
      antiplatelet therapy. Spontaneous dissection of the SMA without aortic dissection
      is very rare, and only 53 cases have been recorded in Japan.

PMID- 19578312
TI  - [A case of diffuse hepatic arteriovenous fistulae with hepatic encephalopathy,
      postprandial abdominal pain and biliary injury].
AB  - A 60-year-old woman with hepatic encephalopathy was admitted to our hospital.
      Ultrasonography, computed tomography and hepatic arteriography revealed diffuse
      hepatic arteriovenous fistulae (HAVF). Overt portosystemic shunt could not be
      identified. Right heart catheterization showed increased cardiac output. However
      the patient had never shown any signs of heart failure. Other than that, marked
      hepatopetal arterial flow from some branches of the superior mesenteric artery
      was detected and mesenteric arterial flow remarkably decreased. Extensive HAVF
      can lead to significant complications, including high output heart failure,
      pulmonary hypertension, portal hypertension, hepatic encephalopathy, biliary
      ischemia, cirrhosis, postprandial abdominal pain, and reduced liver function.
      Embolization or ligation of the hepatic artery provides temporal improvement of
      clinical symptoms, but long-term results are unsatisfactory because of the
      development of collateral circulation and the risk of refractory intrahepatic
      cholangitis, subsequently leading to liver failure. Liver transplantation offers
      another therapeutic option and can be a successful curative treatment.

PMID- 19578313
TI  - [A case of surgical treatment for solitary lymph node recurrence of
      hepatocellular carcinoma simultaneously developed in the mediastinum and
      abdominal cavity].
AB  - We report a surgically treated case of lymph node recurrence from hepatocellular
      carcinoma (HCC) that occurred simultaneously but individually in the mediastinum
      and abdominal cavity with no metastasis. A 52-year-old man had undergone left
      lateral segmentectomy for poorly differentiated HCC. Three months after surgery,
      abdominal computed tomography revealed an enlarged solitary lymph node along the
      common hepatic artery. Another isolated mediastinal lymph node was also positive
      on whole body 18F-fluorodeoxyglucose positron emission tomography. Because no
      other metastatic lesions were identified, we resected these two lymph nodes under
      a diagnosis of lymph node metastases from HCC. Histopathologically, both of them
      were classified as poorly differentiated HCC with solid growth. No further
      recurrence has been found during 20-month follow-up period. Our experience
      suggested that even though metastatic lymph nodes of HCC were present in the
      mediastinum and abdominal cavity, resection may provide survival benefit if each
      metastasis is individually solitary.

PMID- 19578314
TI  - [A case of ruptured giant liver cyst complicated by Candida infection].
AB  - A 75-year-old woman who had been given a diagnosis of a giant liver cyst
      occupying the right hepatic lobe was admitted to our hospital complaining of
      abdominal pain. CT examination revealed the size of cyst was smaller than before
      and the level of CRP was elevated, suggesting the development of peritonitis due
      to rupture of the cyst. As Candida albicans was detected from both ascites and
      the cyst, we treated her with continuous percutaneous transhepatic drainage and
      antimycotic agents. The cyst markedly diminished, and she became free of
      infection and peritonitis, suggesting drainage was exceedingly effective.

PMID- 19578315
TI  - [Carcinoma of the gallbladder which progress on the mucosa of choledochocolonic
      fistula].
AB  - A 70-year-old man was admitted to our hospital for further examination of
      pneumobilia and atrophy in the gallbladder. Abdominal CT scan and EUS revealed
      that the atrophic gallbladder was occupied by a tumor lesion. In addition, ERCP
      showed choledochocolonic fistula. Colonoscopy revealed an elevated lesion in the
      colonic side of fistula, and biopsy of the elevated lesion revealed
      adenocarcinoma. Cholecystectomy and right hemicolectomy was performed under a
      preoperative diagnosis of gallbladder carcinoma with choledochocolonic fistula.
      Pathologically, most of the tumor was localized in the gallbladder, and grew
      along the mucosa of choledchocolonic fistula. This case was of interest with
      regard to the relationship between the choledochocolonic fistula and gallbladder
      carcinoma.

PMID- 19578316
TI  - [A case of pancreatic endocrine tumor developing from intraductal papillary
      mucinous neoplasm (IPMN)].
AB  - In March, 2004, a 64-year-old man was given a diagnosis of IPMN of the pancreas
      in postoperative CT of left shoulder blade chondrosarcoma. In October, 2007,
      because a tumor in the pancreas body was found, distal pancreatectomy was
      performed a diagnosis of the poorly differentiated adenocarcinoma.
      Histopathologic diagnosis revealed as pancreatic endocrine tumor and immunity
      dyeing was useful for differential diagnosis. A case of pancreatic endocrine
      tumor developing from IPMN has a possibility not rare for frequency, but few
      reports are available so far.

PMID- 19578317
TI  - [A case of solitary fibrous tumor of the pancreas].
AB  - A 58-year-old woman without any clinical symptoms had a routine health check-up,
      during which a mass in the head of the pancreas was detected by US. Abdominal US
      showed a round, hypoechogenic nodule of the pancreatic head. The tumor measured
      3cm in diameter and contained an anechoic area. CT revealed a well-demarcated
      tumor in the pancreatic head. The tumor was partially enhanced by contrast
      medium, but the left portion of the tumor, which US had shown to be an anechoic
      area was not enhanced. Imaging findings suggested an endocrine tumor with cystic
      changes. A pylorus-preserving pancreatoduodenectomy was performed. The tumor was
      composed of spindle-shaped cells. There was a typical patternless growth of short
      fascicles and a short storiform arrangement of cells in the stroma with varying
      degrees of collagenization. Immunohistochemically, the tumor cells were positive
      for CD34 and Bcl-2. Based on the light microscopic morphology and immunostaining
      profile, the tumor was classified as a solitary fibrous tumor (SFT) of the
      pancreas.

PMID- 19578318
TI  - Fever control in the neuro-ICU: why, who, and when?
AB  - PURPOSE OF REVIEW: Fever in the neurocritical care setting is very common and has
      a negative impact on outcome of all disease types. Recent advances have made
      eliminating fever and maintaining normothermia feasible. However, important
      questions regarding indications and timing remain. The purpose of this review is
      to analyze the data surrounding the impact of fever across a range of neurologic
      injuries to better understand the optimal timing and duration of fever control.
      RECENT FINDINGS: Meta-analyses have demonstrated that fever at onset and in the
      acute setting after ischemic brain injury, intracerebral hemorrhage, and cardiac
      arrest have a negative impact on morbidity and mortality. There are data to
      support that the impact of fever is sustained for longer durations after
      subarachnoid hemorrhage and traumatic brain injury. However, there are currently
      no prospective randomized trials demonstrating the benefit of fever control in
      these patient populations. SUMMARY: The negative impact of fever after neurologic
      injury is well understood. Prospective randomized trials are needed to determine
      whether the beneficial impact of secondary injury prevention is outweighed by the
      potential infectious risk of prolonged fever control.

PMID- 19578319
TI  - Medical management of acute intracerebral hemorrhage.
AB  - PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) is the most serious but least
      treatable form of stroke, with prognosis critically dependent on both the size
      and degree of hematoma expansion. Treatments that target hematoma expansion offer
      potential to improve outcomes. This review analyzes the recent literature
      pertaining to the medical management of ICH. RECENT FINDINGS: Modern imaging
      studies have confirmed the dynamic nature of ICH. At least one-third of patients
      experience significant continued bleeding and hematoma expansion in the first few
      hours after onset, more so in warfarin-related ICH. Despite a strong biological
      rationale for benefit, a large clinical trial of recombinant activated factor VII
      failed to show any treatment effects on substantive outcomes despite clear
      attenuation of hematoma growth. The impact of recombinant activated factor VII is
      therefore severely restricted because of uncertain efficacy, definite hazard, and
      high cost. Accumulating evidence indicates beneficial effects from the early
      normalization of international normalized ratio levels and replacement of
      coagulation factors in warfarin-related ICH. Although high blood pressure (BP) is
      common and associated with poor outcomes in ICH, there is insufficient evidence
      to recommend a specific early BP management strategy, although recent randomized
      evidence indicates that such treatment is well tolerated and readily incorporated
      into routine clinical practice. Definitive evidence to support a low-cost, widely
      applicable treatment is urgently required for a condition in which therapy is
      primarily supportive. SUMMARY: In patients with acute ICH, rapid intensive BP
      lowering treatment may provide protection against hematoma growth without
      concerns about safety and tolerability. How well such treatment can translate
      into overall benefits to patients is yet to be determined. At present,
      recombinant activated factor VII cannot be recommended for routine use, although
      BP lowering should generally follow conservative guidelines.

PMID- 19578320
TI  - Continuous EEG monitoring: is it ready for prime time?
AB  - PURPOSE OF REVIEW: Continuous electroencephalography (cEEG) is being used more
      frequently in intensive care units to detect epileptic activity and ischemia.
      This review analyzes clinical applications and limitations of cEEG as a routine
      neuromonitoring tool. RECENT FINDINGS: cEEG is primarily used to detect
      nonconvulsive seizures, which are frequent and possibly associated with harm.
      Cerebral ischemia, such as that from vasospasm after subarachnoid hemorrhage, can
      be detected earlier by EEG and quantitative EEG (qEEG). Highly skilled
      technicians and subspecialty-trained physicians are needed to generate good
      quality EEG and to interpret these data. qEEG allows more efficient
      interpretation of large amounts of EEG and may trigger prespecified alarms.
      Currently, there is little high-quality data on cEEG to define indications, cost
      saving potential, and impact on outcome. A few studies have demonstrated how cEEG
      can be integrated into multimodality brain monitoring of severely brain-injured
      patients. SUMMARY: cEEG should be considered as an integral part of multimodality
      monitoring of the injured brain, particularly in patients at risk for
      nonconvulsive seizure or ischemia. Automated alarms may help establish cEEG
      monitoring as an integral part of brain monitoring. All neurological ICUs that
      routinely care for patients with refractory status epilepticus should have the
      capability to perform cEEG monitoring. Further research determining the impact on
      outcome and making EEG monitoring more user friendly may help move this technique
      out of the subspecialized ICU setting into the general ICU environment. In the
      future, it may be possible to use specific EEG parameters as endpoints for
      therapeutic interventions.

PMID- 19578322
TI  - Management of cardiac arrest patients to maximize neurologic outcome.
AB  - PURPOSE OF REVIEW: Each year, hundreds of thousands of people will be
      resuscitated after a cardiac arrest. A significant portion of these patients will
      lapse into a disease state which is the product of modern emergency and critical
      care medicine: the postcardiac arrest syndrome. The ability to return a patient
      to his or her prior state of health after cardiac arrest, once completely beyond
      the capacities of clinicians, is now one of the most important areas of medical
      science. Much of this ability depends on preserving the nervous system from a
      complicated sequence of secondary injuries, which ensue from global ischemia.
      RECENT FINDINGS: The International Liaison Committee On Resuscitation has
      recently given new direction to the care of patients after cardiac arrest by
      addressing the variety of medical problems encountered after resuscitation as a
      single postcardiac arrest syndrome. This paradigm centers on supportive care to
      optimize neurological outcomes and especially focuses on therapeutic hypothermia.
      SUMMARY: This study reviews the latest advances in treating patients after
      cardiac arrest in the emergency department and critical care unit environments.

PMID- 19578323
TI  - Hemicraniectomy for malignant middle cerebral artery infarction.
AB  - PURPOSE OF REVIEW: Space-occupying, malignant hemispheric infarction is one of
      the most devastating forms of ischemic stroke. Several case series had suggested
      decompressive hemicraniectomy as a life-saving therapy, but, until recently,
      there was no proof for this procedure from randomized controlled trials. RECENT
      FINDINGS: In 2007, results from a pooled analysis of three European trials as
      well as data from two of these trials were published and yield compelling
      evidence for the benefit of hemicraniectomy. SUMMARY: Data from the published
      trials leave no doubt about the benefit especially the life-saving character of
      hemicraniectomy for malignant hemispheric infarction. However, some open
      questions (i.e. timing of surgery, age limit for hemicraniectomy) remain to be
      answered in the future.

PMID- 19578321
TI  - Microdialysis: is it ready for prime time?
AB  - PURPOSE OF REVIEW: This review highlights recent advances in cerebral
      microdialysis for investigational and clinical neurochemical monitoring in
      patients with critical neurological conditions. RECENT FINDINGS: Use of
      microdialysis with other methods, including PET, electrophysiological monitoring
      and brain tissue oximetry in traumatic brain injury, subarachnoid hemorrhage with
      vasospasm, and infarction with refractory increased intracranial pressure have
      been reported. Potentially adverse neurochemical effects of nonconvulsive status
      epilepticus and cortical slow depolarization waves, both of which are
      increasingly recognized in traumatic brain injury and stroke patients, have been
      reported. The explosive growth in the use of cerebral oximetry with targeted
      management of brain tissue oxygen levels is leading to greater understanding of
      derangements of cerebral bioenergetics in the critically ill brain, but there
      remain unresolved basic issues. Understanding of the analytes that are measurable
      at the bedside - glucose, lactate, pyruvate, glutamate and glycerol - continues
      to evolve with glucose, lactate, pyruvate and the lactate-pyruvate ratio taking
      center stage. Analytes including inflammatory biomarkers such as cytokines and
      metabolites of nitric oxide are presently investigational, but hold promise for
      future application in advancing our understanding of basic pathophysiology,
      therapeutic target selection and prognostication. Growing consensus on
      indications for use of clinical microdialysis and advances in commercially
      available equipment continue to make microdialysis increasingly 'ready for prime
      time.' SUMMARY: Cerebral microdialysis is an established tool for neurochemical
      research in the ICU. This technique cannot be fruitfully used in isolation, but
      when combined with other monitoring methods provides unique insights into the
      biochemical and physiological derangements in the injured brain.

PMID- 19578324
TI  - When should stress ulcer prophylaxis be used in the ICU?
AB  - PURPOSE OF REVIEW: To discuss the risk factors and underlying illnesses that play
      a role in the pathophysiology of stress ulcer, and to evaluate the evidence
      pertaining to stress ulcer-related bleeding prophylaxis in critically ill
      patients. RECENT FINDINGS: The use of stress ulcer prophylaxis is common in
      critical care medicine and is a major challenge to physicians in the ICU. The
      mechanism of stress ulcer is believed to be multifactorial, yet remains
      incompletely understood. The most widely used drugs for stress ulcer prophylaxis
      are intravenous histamine2-receptor antagonists. They raise gastric pH, but are
      associated with the development of tolerance, possible drug interactions, and
      neurologic manifestations. Sucralfate, which can be administered by the
      nasogastric route, can protect the gastric mucosa without raising pH, but may
      decrease absorption of concomitantly administered oral medications. Proton pump
      inhibitors are the most potent acid-inhibiting pharmacologic agents available.
      Proton pump inhibitors are at least as effective as histamine2-receptor
      antagonists, as a limited number of clinical trials have demonstrated. However,
      these trials were small, lacked an active comparator, varied in the number of
      risk factors, and used a different definition of clinically important bleeding
      than previously established. SUMMARY: Routine prophylaxis against stress ulcers
      in the ICU is not well justified by current evidence. Patients at risk of stress
      ulcer-related bleeding are most likely to benefit from prophylaxis. Thus,
      healthcare professionals should continue to evaluate risk and assess the need for
      stress ulcer-related prophylaxis.

PMID- 19578325
TI  - Clostridium difficile infection: current perspectives.
AB  - PURPOSE OF REVIEW: Clostridium difficile infection (CDI), long-associated with
      morbidity and mortality in healthcare settings, has evolved in recent years with
      unprecedented clinical manifestations. Today, CDI is characterized by unusually
      toxigenic and resistant subtypes, expanded epidemiology, and a growing list of
      risk factors. In this article, we discuss current trends and research for CDI in
      critical care settings, and new controversies that influence clinical practice.
      RECENT FINDINGS: CDI is the focus of intense and comprehensive research. For the
      critical care practitioner, relevant knowledge includes diagnosis of CDI,
      defining the severity of disease, the role of proton pump inhibitors, and
      treatment options for refractory or relapsing disease. SUMMARY: Annually, CDI
      adds billions of dollars to US healthcare costs compared with just a few years
      ago, and reflects a new and profound pattern of morbidity and mortality. As this
      disease changes, our knowledge and practice patterns must adjust to meet the
      current challenge of CDI.

PMID- 19578326
TI  - Practical management of acute liver failure in the Intensive Care Unit.
AB  - PURPOSE OF REVIEW: Acute liver failure is an uncommon condition affecting about
      2500 patients each year in the United States. Optimal medical management in the
      ICU is one of the more important factors impacting survival with or without liver
      transplantation. This review focuses on the practical aspects of the management
      of patients with acute liver failure in the ICU. RECENT FINDINGS: The important
      topics of fluid disturbances, role of the liver biopsy, administration of N
      acetylcysteine, role of hypothermic therapy and management of intracranial
      hypertension, coagulopathy and infection are discussed. Finally, the evaluation,
      management and recent outcomes of liver transplantation candidates are described.
      SUMMARY: The careful management of the patient in the ICU with acute liver
      failure improves the likelihood of survival.

PMID- 19578327
TI  - A Tactile Automated Passive-Finger Stimulator (TAPS).
AB  - Although tactile spatial acuity tests are used in both neuroscience research and
      clinical assessment, few automated devices exist for delivering controlled
      spatially structured stimuli to the skin. Consequently, investigators often apply
      tactile stimuli manually. Manual stimulus application is time consuming, requires
      great care and concentration on the part of the investigator, and leaves many
      stimulus parameters uncontrolled. We describe here a computer-controlled tactile
      stimulus system, the Tactile Automated Passive-finger Stimulator (TAPS), that
      applies spatially structured stimuli to the skin, controlling for onset velocity,
      contact force, and contact duration. TAPS is a versatile, programmable system,
      capable of efficiently conducting a variety of psychophysical procedures. We
      describe the components of TAPS, and show how TAPS is used to administer a two
      interval forced-choice tactile grating orientation test.

PMID- 19578328
TI  - The microfluidic probe: operation and use for localized surface processing.
AB  - Microfluidic devices allow assays to be performed using minute amounts of sample
      and have recently been used to control the microenvironment of cells.
      Microfluidics is commonly associated with closed microchannels which limit their
      use to samples that can be introduced, and cultured in the case of cells, within
      a confined volume. On the other hand, micropipetting system have been used to
      locally perfuse cells and surfaces, notably using push-pull setups where one
      pipette acts as source and the other one as sink, but the confinement of the flow
      is difficult in three dimensions. Furthermore, pipettes are fragile and difficult
      to position and hence are used in static configuration only. The microfluidic
      probe (MFP) circumvents the constraints imposed by the construction of closed
      microfluidic channels and instead of enclosing the sample into the microfluidic
      system, the microfluidic flow can be directly delivered onto the sample, and
      scanned across the sample, using the MFP. . The injection and aspiration openings
      are located within a few tens of micrometers of one another so that a microjet
      injected into the gap is confined by the hydrodynamic forces of the surrounding
      liquid and entirely aspirated back into the other opening. The microjet can be
      flushed across the substrate surface and provides a precise tool for localized
      deposition/delivery of reagents which can be used over large areas by scanning
      the probe across the surface. In this video we present the microfluidic probe
      (MFP). We explain in detail how to assemble the MFP, mount it atop an inverted
      microscope, and align it relative to the substrate surface, and finally show how
      to use it to process a substrate surface immersed in a buffer.

PMID- 19578329
TI  - Born normalization for fluorescence optical projection tomography for whole heart
      imaging.
AB  - Optical projection tomography is a three-dimensional imaging technique that has
      been recently introduced as an imaging tool primarily in developmental biology
      and gene expression studies. The technique renders biological sample optically
      transparent by first dehydrating them and then placing in a mixture of benzyl
      alcohol and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution). The
      technique renders biological samples optically transparent by first dehydrating
      them in graded ethanol solutions then placing them in a mixture of benzyl alcohol
      and benzyl benzoate in a 2:1 ratio (BABB or Murray s Clear solution) to clear.
      After the clearing process the scattering contribution in the sample can be
      greatly reduced and made almost negligible while the absorption contribution
      cannot be eliminated completely. When trying to reconstruct the fluorescence
      distribution within the sample under investigation, this contribution affects the
      reconstructions and leads, inevitably, to image artifacts and quantification
      errors.. While absorption could be reduced further with a permanence of weeks or
      months in the clearing media, this will lead to progressive loss of fluorescence
      and to an unrealistically long sample processing time. This is true when
      reconstructing both exogenous contrast agents (molecular contrast agents) as well
      as endogenous contrast (e.g. reconstructions of genetically expressed fluorescent
      proteins).

PMID- 19578330
TI  - Dendra2 photoswitching through the Mammary Imaging Window.
AB  - In the last decade, intravital microscopy of breast tumors in mice and rats at
      single-cell resolution has resulted in important insights into mechanisms of
      metastatic behavior such as migration, invasion and intravasation of tumor cells,
      angiogenesis, and immune cells response. We have recently reported a technique to
      image orthotopic mammary carcinomas over multiple intravital imaging sessions in
      living mice. For this, we have developed a Mammary Imaging Window (MIW) and
      optimized imaging parameters for Dendra2 photoswitching and imaging in vivo.
      Here, we describe the protocol for the manufacturing of MIW, insertion of the MIW
      on top of a tumor and imaging of the Dendra2- labeled tumor cells using a custom
      built imaging box. This protocol can be used to image the metastatic behavior of
      tumor cells in distinct microenvironments in tumors and allows for long term
      imaging of blood vessels, tumor cells and host cells.

PMID- 19578331
TI  - Using the horseshoe crab, Limulus Polyphemus, in vision research.
AB  - The American horseshoe crab, Limulus Polyphemus is one of the oldest creatures on
      earth, and the animal continues to play an indispensable role in biomedical
      research. Not only does their blood contain special cells that scientists use to
      detect bacteriotoxins in our medicines, but their eyes also contain a neural
      network that has provided much insight about physiological processes operating in
      our visual system, such as light adaptation and lateral inhibition. The horseshoe
      crab remains an attractive model for vision research because the animal is large
      and hardy for an invertebrate, its retinal neurons are big and easily accessible,
      its visual system is compact and extensively studied, and its visual behavior is
      well defined. Moreover, the structure and function of the eyes are modulated on a
      daily basis by a circadian clock in the animal s brain. In short, the visual
      system of horseshoe crabs is simple enough to be understood yet complex enough to
      be interesting. In this video we present three electrophysiological paradigms for
      investigating the neural basis of vision that can be performed in vivo with
      Limulus. They are electroretinogram recording, optic nerve recording, and
      intraretinal recording. Electroretinogram (ERG) recordings measure with a surface
      electrode the summed electrical response of all cells in the eye to a flash of
      light. They can be used to monitor the overall sensitivity of the eye for prolong
      periods of time. Optic nerve recordings measure the spiking activity of single
      nerve fibers with an extracellular microsuction electrode. They can be used to
      study visual messages conveyed from the eye to the brain as well as circadian
      clock messages fed back from the brain to the eye. Intraretinal recordings
      measure with an intracellular microelectrode the voltage fluctuations induced by
      light in individual cells of the eye. They can be used to elucidate cellular
      mechanisms of retinal processing.

PMID- 19578334
TI  - Plasmonic analogue of electromagnetically induced transparency at the Drude
      damping limit.
AB  - In atomic physics, the coherent coupling of a broad and a narrow resonance leads
      to quantum interference and provides the general recipe for electromagnetically
      induced transparency (EIT). A sharp resonance of nearly perfect transmission can
      arise within a broad absorption profile. These features show remarkable potential
      for slow light, novel sensors and low-loss metamaterials. In nanophotonics,
      plasmonic structures enable large field strengths within small mode volumes.
      Therefore, combining EIT with nanoplasmonics would pave the way towards
      ultracompact sensors with extremely high sensitivity. Here, we experimentally
      demonstrate a nanoplasmonic analogue of EIT using a stacked optical metamaterial.
      A dipole antenna with a large radiatively broadened linewidth is coupled to an
      underlying quadrupole antenna, of which the narrow linewidth is solely limited by
      the fundamental non-radiative Drude damping. In accordance with EIT theory, we
      achieve a very narrow transparency window with high modulation depth owing to
      nearly complete suppression of radiative losses.

PMID- 19578332
TI  - Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac
      cell lineages.
AB  - The dual-specificity phosphatase 6 (Dusp6) functions as a feedback regulator of
      fibroblast growth factor (FGF) signaling to limit the activity of extracellular
      signal-regulated kinases (ERKs) 1 and 2. We have identified a small-molecule
      inhibitor of Dusp6-(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1
      one (BCI)-using a transgenic zebrafish chemical screen. BCI treatment blocked
      Dusp6 activity and enhanced FGF target gene expression in zebrafish embryos.
      Docking simulations predicted an allosteric binding site for BCI within the
      phosphatase domain. In vitro studies supported a model in which BCI inhibits
      Dusp6 catalytic activation by ERK2 substrate binding. We used BCI treatment at
      varying developmental stages to uncover a temporal role for Dusp6 in restricting
      cardiac progenitors and controlling heart organ size. This study highlights the
      power of in vivo zebrafish chemical screens to identify new compounds targeting
      Dusp6, a component of the FGF signaling pathway that has eluded traditional high
      throughput in vitro screens.

PMID- 19578333
TI  - Bacillithiol is an antioxidant thiol produced in Bacilli.
AB  - Glutathione is a nearly ubiquitous, low-molecular-mass thiol and antioxidant, but
      it is conspicuously absent from most Gram-positive bacteria. We identify here the
      structure of bacillithiol, a newly described and abundant thiol produced by
      Bacillus species, Staphylococcus aureus and Deinococcus radiodurans. Bacillithiol
      is the alpha-anomeric glycoside of L-cysteinyl-D-glucosamine with L-malic acid
      and most probably functions as an antioxidant. Bacillithiol, like the
      structurally similar mycothiol, may serve as a substitute for glutathione.

PMID- 19578335
TI  - Organic electronics for precise delivery of neurotransmitters to modulate
      mammalian sensory function.
AB  - Significant advances have been made in the understanding of the pathophysiology,
      molecular targets and therapies for the treatment of a variety of nervous-system
      disorders. Particular therapies involve electrical sensing and stimulation of
      neural activity, and significant effort has therefore been devoted to the
      refinement of neural electrodes. However, direct electrical interfacing suffers
      from some inherent problems, such as the inability to discriminate amongst cell
      types. Thus, there is a need for novel devices to specifically interface nerve
      cells. Here, we demonstrate an organic electronic device capable of precisely
      delivering neurotransmitters in vitro and in vivo. In converting electronic
      addressing into delivery of neurotransmitters, the device mimics the nerve
      synapse. Using the peripheral auditory system, we show that out of a diverse
      population of cells, the device can selectively stimulate nerve cells responding
      to a specific neurotransmitter. This is achieved by precise electronic control of
      electrophoretic migration through a polymer film. This mechanism provides several
      sought-after features for regulation of cell signalling: exact dosage
      determination through electrochemical relationships, minimally disruptive
      delivery due to lack of fluid flow, and on-off switching. This technology has
      great potential as a therapeutic platform and could help accelerate the
      development of therapeutic strategies for nervous-system disorders.

PMID- 19578336
TI  - Three-dimensional nanopillar-array photovoltaics on low-cost and flexible
      substrates.
AB  - Solar energy represents one of the most abundant and yet least harvested sources
      of renewable energy. In recent years, tremendous progress has been made in
      developing photovoltaics that can be potentially mass deployed. Of particular
      interest to cost-effective solar cells is to use novel device structures and
      materials processing for enabling acceptable efficiencies. In this regard, here,
      we report the direct growth of highly regular, single-crystalline nanopillar
      arrays of optically active semiconductors on aluminium substrates that are then
      configured as solar-cell modules. As an example, we demonstrate a photovoltaic
      structure that incorporates three-dimensional, single-crystalline n-CdS
      nanopillars, embedded in polycrystalline thin films of p-CdTe, to enable high
      absorption of light and efficient collection of the carriers. Through experiments
      and modelling, we demonstrate the potency of this approach for enabling highly
      versatile solar modules on both rigid and flexible substrates with enhanced
      carrier collection efficiency arising from the geometric configuration of the
      nanopillars.

PMID- 19578337
TI  - Engineering light absorption in semiconductor nanowire devices.
AB  - The use of quantum and photon confinement has enabled a true revolution in the
      development of high-performance semiconductor materials and devices. Harnessing
      these powerful physical effects relies on an ability to design and fashion
      structures at length scales comparable to the wavelength of electrons
      (approximately 1 nm) or photons (approximately 1 microm). Unfortunately, many
      practical optoelectronic devices exhibit intermediate sizes where resonant
      enhancement effects seem to be insignificant. Here, we show that leaky-mode
      resonances, which can gently confine light within subwavelength, high-refractive
      index semiconductor nanostructures, are ideally suited to enhance and spectrally
      engineer light absorption in this important size regime. This is illustrated with
      a series of individual germanium nanowire photodetectors. This notion, together
      with the ever-increasing control over nanostructure synthesis opens up tremendous
      opportunities for the realization of a wide range of high-performance, nanowire
      based optoelectronic devices, including solar cells, photodetectors, optical
      modulators and light sources.

PMID- 19578338
TI  - Milestone: neurology's growth factor: 100 years of Rita Levi-Montalcini.

PMID- 19578339
TI  - Epilepsy: is localization-related epilepsy a progressive disorder? Maybe...

PMID- 19578340
TI  - Dementia: what is behavioral variant frontotemporal dementia?

PMID- 19578341
TI  - Pain: clinical pain assessment: from bedside to better treatment.

PMID- 19578342
TI  - Alzheimer disease: hippocampal volume loss and Alzheimer disease progression.

PMID- 19578343
TI  - Management of new-onset epilepsy in the elderly.
AB  - The incidence of new-onset epilepsy is high among elderly patients. Seizures can
      present differently to and with more subtle semiology than those in younger
      adults. This difference in presentation frequently poses a diagnostic challenge.
      Elderly patients also often have comorbidities, are usually on multiple
      medications that can interact, have altered medication pharmacokinetics, and tend
      to be particularly sensitive to adverse effects of medication. Seizures in the
      elderly tend, however, to respond better to antiepileptic drugs than those in
      younger individuals, and can often be appropriately controlled with monotherapy.
      After the diagnosis of epilepsy is confirmed, treatment should be started with a
      single medication at a low dose, with subsequent gradual upward titration until
      seizures are controlled. First-generation antiepileptic drugs should be avoided
      in the elderly in view of poor tolerability. A large trial has shown that
      lamotrigine and gabapentin are better tolerated than carbamazepine. In elderly
      patients whose seizures remain uncontrolled on antiepileptic medications, surgery
      can be considered if excellent results are predicted and the risks are low.

PMID- 19578344
TI  - Critical illness polyneuropathy and myopathy in the intensive care unit.
AB  - Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are
      major complications that occur in severely ill patients who require intensive
      care treatment. CIP and CIM affect the limb and respiratory muscles, and, as a
      consequence, they characteristically complicate weaning from the ventilator,
      increase the length of stay on the intensive care unit, and prolong physical
      rehabilitation. The basic pathophysiology of both disorders is complex and
      involves metabolic, inflammatory and bioenergetic alterations. It is unclear at
      present whether CIP and CIM are distinct entities, or whether they just represent
      different 'organ' manifestations of a common pathophysiological mechanism. This
      article provides an overview of the clinical and diagnostic features of CIP and
      CIM and discusses current pathophysiological and therapeutic concepts relating to
      these neuromuscular disorders.

PMID- 19578348
TI  - Surgery: centers of excellence for penile prosthesis: yes or no?

PMID- 19578347
TI  - Urinary incontinence: oxybutynin topical gel for overactive bladder.

PMID- 19578346
TI  - Lumbar spinal stenosis: syndrome, diagnostics and treatment.
AB  - Lumbar spinal stenosis (LSS) comprises narrowing of the spinal canal with
      subsequent neural compression, and is frequently associated with symptoms of
      neurogenic claudication. To establish a diagnosis of LSS, clinical history,
      physical examination results and radiological changes all need to be considered.
      Patients who exhibit mild to moderate symptoms of LSS should undergo multimodal
      conservative treatment, such as patient education, pain medication, delordosing
      physiotherapy and epidural injections. In patients with severe symptoms, surgery
      is indicated if conservative treatment proves ineffective after 3-6 months.
      Clinically relevant motor deficits or symptoms of cauda equina syndrome remain
      absolute indications for surgery. The first randomized, prospective studies have
      provided class I-II evidence that supports a more rapid and profound decline of
      LSS symptoms after decompressive surgery than with conservative therapy. In the
      absence of a valid paraclinical diagnostic marker, however, more evidence-based
      data are needed to identify those patients for whom the benefit of surgery would
      outweigh the risk of developing complications. In this Review, we briefly survey
      the underlying pathophysiology and clinical appearance of LSS, and explore the
      available diagnostic and therapeutic options, with particular emphasis on
      neuroradiological findings and outcome predictors.

PMID- 19578345
TI  - Epileptogenesis in the immature brain: emerging mechanisms.
AB  - Epileptogenesis is defined as the process of developing epilepsy-a disorder
      characterized by recurrent seizures-following an initial insult. Seizure
      incidence during the human lifespan is at its highest in infancy and childhood.
      Animal models of epilepsy and human tissue studies suggest that epileptogenesis
      involves a cascade of molecular, cellular and neuronal network alterations.
      Within minutes to days following the initial insult, there are acute early
      changes in neuronal networks, which include rapid alterations to ion channel
      kinetics as a result of membrane depolarization, post-translational modifications
      to existing functional proteins, and activation of immediate early genes.
      Subacute changes occur over hours to weeks, and include transcriptional events,
      neuronal death and activation of inflammatory cascades. The chronic changes that
      follow over weeks to months include anatomical changes, such as neurogenesis,
      mossy fiber sprouting, network reorganization, and gliosis. These epileptogenic
      processes are developmentally regulated and might contribute to differences in
      epileptogenesis between adult and developing brains. Here we review the factors
      responsible for enhanced seizure susceptibility in the developing brain, and
      consider age-specific mechanisms of epileptogenesis. An understanding of these
      factors could yield potential therapeutic targets for the prevention of
      epileptogenesis and also provide biomarkers for identifying patients at risk of
      developing epilepsy or for monitoring disease progression.

PMID- 19578349
TI  - Clinical trials: nationally representative data in urology.

PMID- 19578350
TI  - Risk factors: improved risk stratification for prostate cancer.

PMID- 19578351
TI  - Genetics: susceptibility loci in a molecular subtype of prostate cancer.

PMID- 19578352
TI  - Clinical guidelines: should 5 alpha-reductase inhibitors be used for prostate
      disease?

PMID- 19578353
TI  - Pain: easing the pain: local anesthesia for prostate biopsy.

PMID- 19578354
TI  - Surgery: laparoscopic prostatectomy: learning curve and cancer control.

PMID- 19578355
TI  - Prostate kallikrein markers in diagnosis, risk stratification and prognosis.
AB  - The kallikrein, prostate-specific antigen (PSA), is one of the world's most
      frequently used disease biomarkers. After almost two decades of research and
      clinical experience, the diagnostic and monitoring limitations of PSA are
      beginning to be understood. Most physicians are aware of PSA's low specificity
      for cancer among older men with benign prostatic conditions; fewer are aware of
      recent data, which show that a prior negative biopsy or a prior PSA value below
      the threshold for biopsy might compromise the predictive accuracy of PSA even
      further. Furthermore, a subtle increase in serum PSA level during early middle
      age is strongly correlated with clinically important prostate cancer. We review
      current and past reports on the prostate kallikreins PSA and hK2 in relation to
      pathology and epidemiology.

PMID- 19578356
TI  - A G-CSF-secreting adrenal carcinoma with rhabdoid-like differentiation causing
      leukocytosis.
AB  - BACKGROUND: A 57-year-old African American man presented to a tertiary care
      center with a 6-month history of fatigue and worsening abdominal pain. He had
      lost 9.1 kg in weight in the 3 months leading up to presentation, and described
      subjective fevers and night sweats for 1 month with a nonproductive cough and
      blurred vision for several weeks before presentation. He had chronic renal
      insufficiency, sleep apnea, hypertension, and peripheral vascular disease.
      INVESTIGATIONS: Physical examination, complete blood count, peripheral blood
      smear, leukocyte alkaline phosphatase score, bone marrow biopsy, CT of the chest,
      abdomen, and pelvis, MRI of the abdomen and pelvis, measurement of plasma and
      urine metanephrines, 24 h urine testing for cortisol and 17-ketosteroids,
      measurement of serum granulocyte colony-stimulating factor (G-CSF) level,
      histopathologic examination and immunohistochemical staining of resected tumor.
      DIAGNOSIS: G-CSF-secreting adrenal carcinoma with rhabdoid-like differentiation.
      MANAGEMENT: En bloc surgical resection of kidney, suprarenal mass and spleen was
      performed, followed by initiation of mitotane chemotherapy 3 months later.

PMID- 19578357
TI  - A management algorithm for hematospermia.
AB  - The presence of blood in the semen--hematospermia--is an anxiety-provoking but
      usually self-limiting condition. Its exact incidence remains unclear. The risk of
      underlying malignancy, despite being very low, drives evaluation. There is
      confusion amongst clinicians as to how best to refer, evaluate and treat men with
      hematospermia. We have reviewed the literature in an attempt to present a
      cohesive view of the etiologies and diagnostic and management strategies in
      patients with this condition.

PMID- 19578358
TI  - miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.
AB  - MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a
      single miRNA that can efficiently differentiate multipotent stem cells into a
      specific lineage or regulate direct reprogramming of cells into an alternative
      cell fate has been elusive. Here we show that miR-145 and miR-143 are co
      transcribed in multipotent murine cardiac progenitors before becoming localized
      to smooth muscle cells, including neural crest stem-cell-derived vascular smooth
      muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum
      response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5)
      and were downregulated in injured or atherosclerotic vessels containing
      proliferating, less differentiated smooth muscle cells. miR-145 was necessary for
      myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and
      sufficient to induce differentiation of multipotent neural crest stem cells into
      vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a
      network of transcription factors, including Klf4 (Kruppel-like factor 4),
      myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote
      differentiation and repress proliferation of smooth muscle cells. These findings
      demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and
      miR-143 function to regulate the quiescent versus proliferative phenotype of
      smooth muscle cells.

PMID- 19578359
TI  - Partial penetrance facilitates developmental evolution in bacteria.
AB  - Development normally occurs similarly in all individuals within an isogenic
      population, but mutations often affect the fates of individual organisms
      differently. This phenomenon, known as partial penetrance, has been observed in
      diverse developmental systems. However, it remains unclear how the underlying
      genetic network specifies the set of possible alternative fates and how the
      relative frequencies of these fates evolve. Here we identify a stochastic cell
      fate determination process that operates in Bacillus subtilis sporulation mutants
      and show how it allows genetic control of the penetrance of multiple fates.
      Mutations in an intercompartmental signalling process generate a set of discrete
      alternative fates not observed in wild-type cells, including rare formation of
      two viable 'twin' spores, rather than one within a single cell. By genetically
      modulating chromosome replication and septation, we can systematically tune the
      penetrance of each mutant fate. Furthermore, signalling and replication
      perturbations synergize to significantly increase the penetrance of twin
      sporulation. These results suggest a potential pathway for developmental
      evolution between monosporulation and twin sporulation through states of
      intermediate twin penetrance. Furthermore, time-lapse microscopy of twin
      sporulation in wild-type Clostridium oceanicum shows a strong resemblance to twin
      sporulation in these B. subtilis mutants. Together the results suggest that noise
      can facilitate developmental evolution by enabling the initial expression of
      discrete morphological traits at low penetrance, and allowing their stabilization
      by gradual adjustment of genetic parameters.

PMID- 19578360
TI  - A role for Lin28 in primordial germ-cell development and germ-cell malignancy.
AB  - The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in
      the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell
      specification. stella (also called Dppa3) marks the rare founder population of
      the germ lineage. Here we differentiate mouse embryonic stem cells carrying a
      stella transgenic reporter into putative PGCs in vitro. The Stella(+) cells
      possess a transcriptional profile similar to embryo-derived PGCs, and like their
      counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory
      RNAs to screen candidate genes for effects on the development of Stella(+) cells
      in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA
      processing, is essential for proper PGC development. Furthermore, we show that
      Blimp1 (also called Prdm1), a let-7 target and a master regulator of PGC
      specification, can rescue the effect of Lin28 deficiency during PGC development,
      thereby establishing a mechanism of action for Lin28 during PGC specification.
      Overexpression of Lin28 promotes formation of Stella(+) cells in vitro and PGCs
      in chimaeric embryos, and is associated with human germ-cell tumours. The
      differentiation of putative PGCs from embryonic stem cells in vitro recapitulates
      the early stages of gamete development in vivo, and provides an accessible system
      for discovering novel genes involved in germ-cell development and malignancy.

PMID- 19578361
TI  - Structure of a prokaryotic virtual proton pump at 3.2 A resolution.
AB  - To reach the mammalian gut, enteric bacteria must pass through the stomach. Many
      such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by
      mounting extreme acid-resistance responses, one of which, the arginine-dependent
      system of Escherichia coli, has been studied at levels of cellular physiology,
      molecular genetics and protein biochemistry. This multiprotein system keeps the
      cytoplasm above pH 5 during acid challenge by continually pumping protons out of
      the cell using the free energy of arginine decarboxylation. At the heart of the
      process is a 'virtual proton pump' in the inner membrane, called AdiC, that
      imports L-arginine from the gastric juice and exports its decarboxylation product
      agmatine. AdiC belongs to the APC superfamily of membrane proteins, which
      transports amino acids, polyamines and organic cations in a multitude of
      biological roles, including delivery of arginine for nitric oxide synthesis,
      facilitation of insulin release from pancreatic beta-cells, and, when
      inappropriately overexpressed, provisioning of certain fast-growing neoplastic
      cells with amino acids. High-resolution structures and detailed transport
      mechanisms of APC transporters are currently unknown. Here we describe a crystal
      structure of AdiC at 3.2 A resolution. The protein is captured in an outward
      open, substrate-free conformation with transmembrane architecture remarkably
      similar to that seen in four other families of apparently unrelated transport
      proteins.

PMID- 19578362
TI  - The AP-1 transcription factor Batf controls T(H)17 differentiation.
AB  - Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of
      JUN, FOS, MAF and activating transcription factor (ATF) family proteins
      characterized by basic region and leucine zipper domains. Many AP-1 proteins
      contain defined transcriptional activation domains, but BATF and the closely
      related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are
      considered to be inhibitors of AP-1 activity. Here we show that Batf is required
      for the differentiation of IL17-producing T helper (T(H)17) cells. T(H)17 cells
      comprise a CD4(+) T-cell subset that coordinates inflammatory responses in host
      defence but is pathogenic in autoimmunity. Batf(-/-) mice have normal T(H)1 and
      T(H)2 differentiation, but show a defect in T(H)17 differentiation, and are
      resistant to experimental autoimmune encephalomyelitis. Batf(-/-) T cells fail to
      induce known factors required for T(H)17 differentiation, such as RORgamma t
      (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of
      IL21 nor the overexpression of RORgamma t fully restores IL17 production in Batf(
      /-) T cells. The Il17 promoter is BATF-responsive, and after T(H)17
      differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f
      locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results
      demonstrate that the AP-1 protein BATF has a critical role in T(H)17
      differentiation.

PMID- 19578363
TI  - New common variants affecting susceptibility to basal cell carcinoma.
AB  - In a follow-up to our previously reported genome-wide association study of
      cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility
      variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5)
      gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near
      CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P
      = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR =
      1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental
      origin of the risk allele. None of these variants were found to be associated
      with melanoma or fair-pigmentation traits. A melanoma- and pigmentation
      associated variant in the SLC45A2 gene, L374F, is associated with risk of both
      BCC and squamous cell carcinoma. Finally, we report conclusive evidence that
      rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects
      against melanoma.

PMID- 19578364
TI  - Genome-wide association study identifies three loci associated with melanoma
      risk.
AB  - We report a genome-wide association study of melanoma conducted by the GenoMEL
      consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336
      controls, with replication in an additional two cohorts (1,149 selected cases and
      964 controls from GenoMEL, and a population-based case-control study in Leeds of
      1,163 cases and 903 controls). The genome-wide screen identified five loci with
      genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were
      replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322),
      11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent
      to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are
      associated with pigmentation, freckling and cutaneous sun sensitivity, well
      recognized melanoma risk factors. Common variants within the 9p21 locus have not
      previously been associated with melanoma. Despite wide variation in allele
      frequency, these genetic variants show notable homogeneity of effect across
      populations of European ancestry living at different latitudes and show
      independent association to disease risk.

PMID- 19578365
TI  - Genome-wide association study identifies variants at 9p21 and 22q13 associated
      with development of cutaneous nevi.
AB  - A high melanocytic nevi count is the strongest known risk factor for cutaneous
      melanoma. We conducted a genome-wide association study for nevus count using
      297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107
      individuals. We identified strongly associated variants in MTAP, a gene adjacent
      to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, combined
      P = 3.4 x 10(-15)), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4
      x 10(-8)). In addition, variants in these two loci showed association with
      melanoma risk in 3,131 melanoma cases from two independent studies, including
      rs10757257 at 9p21, combined P = 3.4 x 10(-8), OR = 1.23 (95% CI = 1.15-1.30) and
      rs132985 at 22q13.1, combined P = 2.6 x 10(-7), OR = 1.23 (95% CI = 1.15-1.30).
      This provides the first report of common variants associated to nevus number and
      demonstrates association of these variants with melanoma susceptibility.

PMID- 19578366
TI  - Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma
      susceptibility.
AB  - The causes of glioblastoma and other gliomas remain obscure. To discover new
      candidate genes influencing glioma susceptibility, we conducted a principal
      component-adjusted genome-wide association study (GWAS) of 275,895 autosomal
      variants among 692 adult high-grade glioma cases (622 from the San Francisco
      Adult Glioma Study (AGS) and 70 from the Cancer Genome Atlas (TCGA)) and 3,992
      controls (602 from AGS and 3,390 from Illumina iControlDB (iControls)). For
      replication, we analyzed the 13 SNPs with P < 10(-6) using independent data from
      176 high-grade glioma cases and 174 controls from the Mayo Clinic. On 9p21,
      rs1412829 near CDKN2B had discovery P = 3.4 x 10(-8), replication P = 0.0038 and
      combined P = 1.85 x 10(-10). On 20q13.3, rs6010620 intronic to RTEL1 had
      discovery P = 1.5 x 10(-7), replication P = 0.00035 and combined P = 3.40 x 10(
      9). For both SNPs, the direction of association was the same in discovery and
      replication phases.

PMID- 19578367
TI  - Genome-wide association study identifies five susceptibility loci for glioma.
AB  - To identify risk variants for glioma, we conducted a meta-analysis of two genome
      wide association studies by genotyping 550K tagging SNPs in a total of 1,878
      cases and 3,670 controls, with validation in three additional independent series
      totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma
      at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P =
      2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33
      (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x
      10(-8)). These data show that common low-penetrance susceptibility alleles
      contribute to the risk of developing glioma and provide insight into disease
      causation of this primary brain tumor.

PMID- 19578368
TI  - Identification of a human helper T cell population that has abundant production
      of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells.
AB  - Interleukin 22 (IL-22) is a member of the IL-10 cytokine family that is involved
      in inflammatory and wound healing processes. Originally considered a T helper
      type 1 (T(H)1)-associated cytokine, IL-22 has since been shown to be produced
      mainly by IL-17-producing helper T cells (T(H)-17 cells). Here we describe a
      previously uncharacterized IL-22-producing human helper T cell population that
      coexpressed the chemokine receptor CCR6 and the skin-homing receptors CCR4 and
      CCR10. These cells were distinct from both T(H)-17 cells and T(H)1 cells.
      Downregulation of either the aryl hydrocarbon receptor (AHR) or the transcription
      factor RORC by RNA-mediated interference affected IL-22 production, whereas IL-17
      production was affected only by downregulation of RORC by RNA-mediated
      interference. AHR agonists substantially altered the balance of IL-22- versus IL
      17-producing cells. This subset of IL-22-producing cells may be important in skin
      homeostasis and pathology.

PMID- 19578369
TI  - Production of interleukin 22 but not interleukin 17 by a subset of human skin
      homing memory T cells.
AB  - Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T
      cells and NK-22 subset of natural killer cells that acts on epithelial cells and
      keratinocytes and has been linked to skin homeostasis and inflammation. Here we
      characterize a population of human skin-homing memory CD4(+) T cells that
      expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but
      neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this
      population produced IL-22 only and had low or undetectable expression of the T(H)
      17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The
      differentiation of T cells producing only IL-22 was efficiently induced in naive
      T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor
      dependent way. Our findings delineate a previously unknown subset of human CD4(+)
      effector T cells dedicated to skin pathophysiology.

PMID- 19578370
TI  - Reversible acetylation of the chromatin remodelling complex NoRC is required for
      non-coding RNA-dependent silencing.
AB  - The SNF2h (sucrose non-fermenting protein 2 homologue)-containing chromatin
      remodelling complex NoRC silences a fraction of ribosomal RNA genes (rDNA) by
      establishing a heterochromatic structure at the rDNA promoter. Here we show that
      the acetyltransferase MOF (males absent on the first) acetylates TIP5, the
      largest subunit of NoRC, at a single lysine residue, K633, adjacent to the TIP5
      RNA-binding domain, and that the NAD(+)-dependent deacetylase SIRT1 (sirtuin-1)
      removes the acetyl group from K633. Acetylation regulates the interaction of NoRC
      with promoter-associated RNA (pRNA), which in turn affects heterochromatin
      formation, nucleosome positioning and rDNA silencing. Significantly, NoRC
      acetylation is responsive to the intracellular energy status and fluctuates
      during S phase. Activation of SIRT1 on glucose deprivation leads to deacetylation
      of K633, enhanced pRNA binding and an increase in heterochromatic histone marks.
      These results suggest a mechanism that links the epigenetic state of rDNA to cell
      metabolism and reveal another layer of epigenetic control that involves post
      translational modification of a chromatin remodelling complex.

PMID- 19578371
TI  - BCOR regulates mesenchymal stem cell function by epigenetic mechanisms.
AB  - The BCL-6 co-repressor (BCOR) represses gene transcription by interacting with
      BCL-6 (Refs 1, 2). BCOR mutation is responsible for oculo-facio-cardio-dental
      (OFCD) syndrome, which is characterized by canine teeth with extremely long
      roots, congenital cataracts, craniofacial defects and congenital heart disease.
      Here we show that BCOR mutation increased the osteo-dentinogenic potential of
      mesenchymal stem cells (MSCs) isolated from a patient with OFCD, providing a
      molecular explanation for abnormal root growth. AP-2alpha was identified as a
      repressive target of BCOR, and BCOR mutation resulted in abnormal activation of
      AP-2alpha. Gain- and loss-of-function assays suggest that AP-2alpha is a key
      factor that mediates the increased osteo-dentinogenic capacity of MSCs. Moreover,
      we found that BCOR maintained tissue homeostasis and gene silencing through
      epigenetic mechanisms. BCOR mutation increased histone H3K4 and H3K36 methylation
      in MSCs, thereby reactivating transcription of silenced target genes. By studying
      a rare human genetic disease, we have unravelled an epigenetic mechanism for
      control of human adult stem cell function.

PMID- 19578374
TI  - Welcoming the best and the brightest from everywhere.

PMID- 19578372
TI  - Mitochondrial fission factor Drp1 is essential for embryonic development and
      synapse formation in mice.
AB  - Mitochondrial morphology is dynamically controlled by a balance between fusion
      and fission. The physiological importance of mitochondrial fission in vertebrates
      is less clearly defined than that of mitochondrial fusion. Here we show that mice
      lacking the mitochondrial fission GTPase Drp1 have developmental abnormalities,
      particularly in the forebrain, and die after embryonic day 12.5. Neural cell
      specific (NS) Drp1(-/-) mice die shortly after birth as a result of brain
      hypoplasia with apoptosis. Primary culture of NS-Drp1(-/-) mouse forebrain showed
      a decreased number of neurites and defective synapse formation, thought to be due
      to aggregated mitochondria that failed to distribute properly within the cell
      processes. These defects were reflected by abnormal forebrain development and
      highlight the importance of Drp1-dependent mitochondrial fission within highly
      polarized cells such as neurons. Moreover, Drp1(-/-) murine embryonic fibroblasts
      and embryonic stem cells revealed that Drp1 is required for a normal rate of
      cytochrome c release and caspase activation during apoptosis, although
      mitochondrial outer membrane permeabilization, as examined by the release of
      Smac/Diablo and Tim8a, may occur independently of Drp1 activity.

PMID- 19578373
TI  - Histone levels are regulated by phosphorylation and ubiquitylation-dependent
      proteolysis.
AB  - Histone levels are tightly regulated to prevent harmful effects such as genomic
      instability and hypersensitivity to DNA-damaging agents due to the accumulation
      of these highly basic proteins when DNA replication slows down or stops. Although
      chromosomal histones are stable, excess (non-chromatin bound) histones are
      rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in
      Saccharomyces cerevisiae. Here we demonstrate that excess histones associate with
      Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation
      and polyubiquitylation, before their proteolysis by the proteasome. We have
      identified the Tyr 99 residue of histone H3 as being critical for the efficient
      ubiquitylation and degradation of this histone. We have also identified the
      ubiquitin conjugating enzymes (E2) Ubc4 and Ubc5, as well as the ubiquitin ligase
      (E3) Tom1 (temperature dependent organization in mitotic nucleus 1), as enzymes
      involved in the ubiquitylation of excess histones. Regulated histone proteolysis
      has major implications for the maintenance of epigenetic marks on chromatin,
      genomic stability and the packaging of sperm DNA.

PMID- 19578375
TI  - WDR5, a complexed protein.

PMID- 19578376
TI  - Energetics of protein hydrogen bonds.

PMID- 19578378
TI  - Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin
      type B at 2.0 A resolution.

PMID- 19578379
TI  - Representation of internal models of action in the autistic brain.
AB  - Children with autism spectrum disorder (ASD) have deficits in motor control,
      imitation and social function. Does a dysfunction in the neural basis of
      representing internal models of action contribute to these problems? We measured
      patterns of generalization as children learned to control a novel tool and found
      that the autistic brain built a stronger than normal association between self
      generated motor commands and proprioceptive feedback; furthermore, the greater
      the reliance on proprioception, the greater the child's impairments in social
      function and imitation.

PMID- 19578380
TI  - Genetic identification of an embryonic parafacial oscillator coupling to the
      preBotzinger complex.
AB  - The hindbrain transcription factors Phox2b and Egr2 (also known as Krox20) are
      linked to the development of the autonomic nervous system and rhombomere-related
      regulation of breathing, respectively. Mutations in these proteins can lead to
      abnormal breathing behavior as a result of an alteration in an unidentified
      neuronal system. We characterized a bilateral embryonic parafacial (e-pF)
      population of rhythmically bursting neurons at embryonic day (E) 14.5 in mice.
      These cells expressed Phox2b, were derived from Egr2-expressing precursors and
      their development was dependent on the integrity of the Egr2 gene. Silencing or
      eliminating the e-pF oscillator, but not the putative inspiratory oscillator
      (preBotzinger complex, preBotC), led to an abnormally slow rhythm, demonstrating
      that the e-pF controls the respiratory rhythm. The e-pF oscillator, the only one
      active at E14.5, entrained and then coupled with the preBotC, which emerged
      independently at E15.5. These data establish the dual organization of the
      respiratory rhythm generator at the time of its inception, when it begins to
      drive fetal breathing.

PMID- 19578381
TI  - Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo
      cerebellar motor learning.
AB  - Although feedforward inhibition onto Purkinje cells was first documented 40 years
      ago, we understand little of how inhibitory interneurons contribute to cerebellar
      function in behaving animals. Using a mouse line (PC-Deltagamma2) in which
      GABA(A) receptor-mediated synaptic inhibition is selectively removed from
      Purkinje cells, we examined how feedforward inhibition from molecular layer
      interneurons regulates adaptation of the vestibulo-ocular reflex. Although
      impairment of baseline motor performance was relatively mild, the ability to
      adapt the phase of the vestibulo-ocular reflex and to consolidate gain
      adaptations was strongly compromised. Purkinje cells showed abnormal patterns of
      simple spikes, both during and in the absence of evoked compensatory eye
      movements. On the basis of modeling our experimental data, we propose that
      feedforward inhibition, by controlling the fine-scale patterns of Purkinje cell
      activity, enables the induction of plasticity in neurons of the cerebellar and
      vestibular nuclei.

PMID- 19578382
TI  - Disparity- and velocity-based signals for three-dimensional motion perception in
      human MT+.
AB  - How does the primate visual system encode three-dimensional motion? The macaque
      middle temporal area (MT) and the human MT complex (MT+) have well-established
      sensitivity to two-dimensional frontoparallel motion and static disparity.
      However, evidence for sensitivity to three-dimensional motion has remained
      elusive. We found that human MT+ encodes two binocular cues to three-dimensional
      motion: changing disparities over time and interocular comparisons of retinal
      velocities. By varying important properties of moving dot displays, we
      distinguished these three-dimensional motion signals from their constituents,
      instantaneous binocular disparity and monocular retinal motion. An adaptation
      experiment confirmed direction selectivity for three-dimensional motion. Our
      results indicate that MT+ carries critical binocular signals for three
      dimensional motion processing, revealing an important and previously overlooked
      role for this well-studied brain area.

PMID- 19578383
TI  - Mass spectrometry of membrane transporters reveals subunit stoichiometry and
      interactions.
AB  - We describe a general mass spectrometry approach to determine subunit
      stoichiometry and lipid binding in intact membrane protein complexes. By
      exploring conditions for preserving interactions during transmission into the gas
      phase and for optimally stripping away detergent, by subjecting the complex to
      multiple collisions, we released the intact complex largely devoid of detergent.
      This enabled us to characterize both subunit stoichiometry and lipid binding in 4
      membrane protein complexes.

PMID- 19578384
TI  - Conditional and reversible disruption of essential herpesvirus proteins.
AB  - Elucidating the function of essential proteins of complex pathogenic viruses is
      impeded by a paucity of complementing systems. By fusing a destabilizing domain
      of the FK506-binding protein to essential cytomegalovirus proteins, we generated
      virus mutants in which amounts of fusion proteins and viral growth can be
      regulated by the synthetic ligand shield-1. This conditional approach will
      greatly facilitate the analysis of gene functions of herpesviruses and viruses of
      other families.

PMID- 19578385
TI  - Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the
      TNFRSF11A gene in a Chinese family.
AB  - AIM: A previous study showed that individuals of Japanese descent affected by
      early onset familial Paget's disease of bone (PDB) carried a 27-bp duplication at
      position 75 (75dup27) in the TNFRSF11A gene encoding RANK. Here we report the
      identification of a novel mutation (78dup27) in exon 1 of TNFRSF11A in a Chinese
      family with early onset PDB. METHODS: We conducted clinical and genetic studies
      in a non-consanguineous Chinese family with early onset PDB. The entire coding
      region of TNFRSF11A was amplified and directly sequenced directly. RESULTS: A
      novel 27-bp duplication in exon 1 (78dup27) in TNFRSF11A was found in four
      affected individuals and one asymptomatic individual. Although this duplication
      was the same length as the previously identified mutation (27 bp, from bases 78
      to 104), in our patients the nine duplicated amino acids in the RANK signal
      peptide were LLLLCALLA. The phenotypes of affected individuals in this family
      overlapped with both early onset PDB and classic PDB, but several distinguishing
      features were found in our patients. The key difference between our familial PDB
      and the Japanese early onset PDB was the age of onset, which in most of our
      patients was during their late 20s (except for the propositus' niece). Another
      notable difference was that the propositus' son (24 years old), who carried the
      78dup27 mutation, had no clinical symptoms or bone abnormalities, except for
      increased serum ALP, OC and CTX. CONCLUSION: Our findings may provide a better
      understanding of the clinical features of early onset PDB and support the notion
      of a hot spot for mutations in exon 1 of the TNFRSF11A gene.

PMID- 19578386
TI  - Silibinin inhibits prostate cancer invasion, motility and migration by
      suppressing vimentin and MMP-2 expression.
AB  - AIM: Silibinin is known to exert growth inhibition and cell death together with
      cell cycle arrest and apoptosis in human prostate cancer cells. Whether silibinin
      could inhibit the invasion, motility and migration of prostate cancer cells
      remains largely unknown. This study was designed to evaluate this efficacy and
      possible mechanisms using a novel highly bone metastatic ARCaP(M) cell model.
      METHODS: Four prostate cancer cell lines, LNCaP, PC-3, DU145, and ARCaP(M), were
      used in this study. These cells were treated with increasing concentrations of
      silibinin (50, 100, and 200 micromol/L) for different periods of time. After
      treatment, cell viabilities of four prostate cancer cells were compared by MTT
      assay. Alterations of ARCaP(M) cell invasion, motility and migration were
      assessed by cell invasion, motility and wound healing assays. The changes of
      vimentin expression were observed by Western blotting and immunofluorescence
      staining, and the expression of MMP-2, MMP-9, and uPA was analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: ARCaP(M) cells showed
      less sensitivity to the growth inhibition of pharmacological doses of silibinin
      than LNCaP, PC-3, and DU145 cells. However, silibinin exerted significant dose-
      and time-dependent inhibitory effects on the invasion, motility and migration of
      ARCaP(M) cells. Furthermore, the expression of vimentin and MMP-2, but not MMP-9
      or uPA, was down-regulated in a dose- and time-dependent manner after treatment
      of silibinin. CONCLUSION: This study shows that silibinin could inhibit the
      invasion, motility and migration of ARCaP(M) cells via down-regulation of
      vimentin and MMP-2 and therefore may be a promising agent against prostate cancer
      bone metastasis.

PMID- 19578387
TI  - Transformation of human liver L-O2 cells mediated by stable HBx transfection.
AB  - AIM: To explore the mechanism of hepatocarcinogenesis associated with the
      hepatitis B virus X protein (HBx), we investigated the role of HBx in
      transformation using human liver L-O2 cells stably transfected with HBx as a
      model. METHODS: Plasmids encoding HBx were stably transfected into immortalized
      human liver L-O2 cells and rodent fibroblast NIH/3T3 cells. The expression of
      alfa-fetoprotein (AFP), c-Myc, HBx, and survivin in the engineered cells was
      examined by Western blotting. The malignant phenotype of the cells was
      demonstrated by anchorage-independent colony formation and tumor formation in
      nude mice. RNA interference assays, Western blotting, luciferase reporter gene
      assays and flow cytometry analysis were performed. The number of centrosomes in
      the L-O2-X cells was determined by gamma-tubulin immunostaining. The effect of
      HBx on the transcriptional activity of human telomerase reverse transcriptase
      (hTERT) and hTERT activity in L-O2-X cells and/or 3T3-X cells was detected by the
      luciferase reporter gene assay and telomerase repeat amplification protocol
      (TRAP). RESULTS: Stable HBx transfection resulted in a malignant phenotype in the
      engineered cells in vivo and in vitro. Meanwhile, HBx was able to increase the
      transcription of the NF-kappaB, AP-1, and survivin genes and to upregulate the
      expression levels of c-Myc and survivin. Abnormal centrosome duplication and
      activated hTERT were responsible for the transformation. CONCLUSION: Stable HBx
      transfection leads to genomic instability of host cells, which is responsible for
      hepatocarcinogenesis; meanwhile, transactivation by the HBx protein contributes
      to the development of hepatocellular carcinoma (HCC). The L-O2-X cell line is an
      ideal model for investigating the mechanism of HBx-mediated transformation.

PMID- 19578388
TI  - Novel 16-substituted bifunctional derivatives of huperzine B: multifunctional
      cholinesterase inhibitors.
AB  - AIM: To design novel bifunctional derivatives of huperzine B (HupB) based on the
      concept of dual binding site of acetylcholinesterase (AChE) and evaluate their
      pharmacological activities for seeking new drug candidates against Alzheimer's
      disease (AD). METHODS: Novel 16-substituted bifunctional derivatives of HupB were
      synthesized through chemical reactions. The inhibitory activities of the
      derivatives toward AChE and butyrylcholinesterase (BuChE) were determined in
      vitro by modified Ellman's method. Cell viability was quantified by the reduction
      of MTT. RESULTS: A new preparative method was developed for the generation of 16
      substituted derivatives of HupB, and pharmacological trials indicated that the
      derivatives were multifunctional cholinesterase inhibitors targeting both AChE
      and BuChE. Among the derivatives tested, 9c, 9e, 9f, and 9i were 480 to 1360
      times more potent as AChE inhibitors and 370 to 1560 times more potent as BuChE
      inhibitors than the parent HupB. Further preliminary pharmacological trials of
      derivatives 9c and 9i were performed, including examining the mechanism of AChE
      inhibition, the substrate kinetics of the enzyme inhibition, and protection
      against hydrogen peroxide (H2O2)-induced cytotoxicity in PC12 cells. CONCLUSION:
      Preliminary pharmacological evaluation indicated that 16-substituted derivatives
      of HupB, particularly 9c and 9i, would be potentially valuable new drug
      candidates for AD therapy, and further exploration is needed to evaluate their
      pharmacological and clinical efficacies.

PMID- 19578389
TI  - High K+-induced contraction requires depolarization-induced Ca2+ release from
      internal stores in rat gut smooth muscle.
AB  - AIM: Depolarization-induced contraction of smooth muscle is thought to be
      mediated by Ca2+ influx through voltage-gated L-type Ca2+channels. We describe a
      novel contraction mechanism that is independent of Ca2+ entry. METHODS:
      Pharmacological experiments were carried out on isolated rat gut longitudinal
      smooth muscle preparations, measuring isometric contraction strength upon high K+
      induced depolarization. RESULTS: Treatment with verapamil, which presumably leads
      to a conformational change in the channel, completely abolished K+-induced
      contraction, while residual contraction still occurred when Ca2+ entry was
      blocked with Cd2+. These results were further confirmed by measuring
      intracellular Ca2+ transients using Fura-2. Co-application of Cd2+ and the
      ryanodine receptor blocker DHBP further reduced contraction, albeit incompletely.
      Additional blockage of either phospholipase C (U 73122) or inositol 1,4,5
      trisphophate (IP3)receptors (2-APB) abolished most contractions, while sole
      application of these blockers and Cd2+ (without parallel ryanodine receptor
      manipulation) also resulted in incomplete contraction block. CONCLUSION: We
      conclude that there are parallel mechanisms of depolarization-induced smooth
      muscle contraction via (a) Ca2+ entry and (b) Ca2+ entry-independent,
      depolarization-induced Ca2+-release through ryanodine receptors and IP3, with the
      latter being dependent on phospholipase C activation.

PMID- 19578390
TI  - Anticitrullinated protein/peptide antibodies in rheumatoid arthritis.

PMID- 19578391
TI  - The serological diagnosis of rheumatoid arthritis: antibodies to citrullinated
      antigens.
AB  - BACKGROUND: This article provides an overview of modern serological diagnostic
      testing for rheumatoid arthritis (RA) involving the detection of antibodies
      against citrullinated peptides/proteins (ACPA). Recommendations are also given
      for differential diagnosis and sequential testing in rheumatoid arthritis, with a
      view towards improving early diagnosis, so that irreparable joint damage can be
      avoided. METHODS: Selective literature research, with consideration of the
      authors' own publications. RESULTS: Two different, adequately evaluated testing
      systems, involving the detection of anti-CCP antibodies and of anti-MCV
      antibodies, are now commercially available and enable routine, relatively highly
      specific diagnostic testing for RA. Two point-of-care tests (POCT) for the early
      diagnosis of RA constitute the latest development in serologic diagnostic
      testing. CONCLUSIONS: The two ACPA assays now on the market are equally useful
      for the diagnosis of rheumatoid arthritis. The correlation between RA disease
      activity and stratification with ACPA has only been demonstrated to date through
      the detection of anti-MCV antibodies.

PMID- 19578392
TI  - Sleep-disordered breathing in patients with atrial fibrillation and normal
      systolic left ventricular function.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is more common in patients with atrial
      fibrillation (AFib). Recently, an additional association between central sleep
      apnea/Cheyne-Stokes respiration (CSA/CSR) and AFib has been described. The aim of
      this study was to investigate the prevalence and type of sleep-disordered
      breathing in patients with AFib and normal systolic left ventricular function.
      METHODS: 150 patients (110 men and 40 women, aged 66.1 +/- 1.7 years) underwent
      cardiorespiratory polygraphy, capillary blood gas analysis, measurement of NT
      proBNP, and echocardiography to determine the diameter of the left atrium (LAD)
      and the peak systolic pulmonary artery pressure (PAP). RESULTS: Sleep-disordered
      breathing was documented in 74% of all patients with AFib (43% had OSA and 31%
      had CSA/CSR). Patients with CSA/CSR had a higher PAP, a higher apnea-hypopnea
      index, a greater LAD, and a lower capillary blood pCO(2) than patients with OSA.
      CONCLUSIONS: Patients with AFib were found to have not only a high prevalence of
      obstructive sleep apnea, as has been described previously, but also a high
      prevalence of CSA/CSR. It remains unknown whether CSA/CSR is more common in AFib
      because of diastolic dysfunction or whether phenomena associated with CSA/CSR
      predispose to AFib. Further research on this question is needed.

PMID- 19578393
TI  - Re: Management of patients with aortic dissection. Etiology was incomplete.

PMID- 19578395
TI  - Re: Management of patients with aortic dissection. New insights.

PMID- 19578396
TI  - Re: Mastocytosis--a disease of the hematopoietic stem cell. Problematic criteria.

PMID- 19578398
TI  - Positional cloning of zinc finger domain transcription factor Zfp69, a candidate
      gene for obesity-associated diabetes contributed by mouse locus Nidd/SJL.
AB  - Polygenic type 2 diabetes in mouse models is associated with obesity and results
      from a combination of adipogenic and diabetogenic alleles. Here we report the
      identification of a candidate gene for the diabetogenic effect of a QTL
      (Nidd/SJL, Nidd1) contributed by the SJL, NON, and NZB strains in outcross
      populations with New Zealand Obese (NZO) mice. A critical interval of distal
      chromosome 4 (2.1 Mbp) conferring the diabetic phenotype was identified by
      interval-specific congenic introgression of SJL into diabetes-resistant C57BL/6J,
      and subsequent reporter cross with NZO. Analysis of the 10 genes in the critical
      interval by sequencing, qRT-PCR, and RACE-PCR revealed a striking allelic
      variance of Zfp69 encoding zinc finger domain transcription factor 69. In NZO and
      C57BL/6J, a retrotransposon (IAPLTR1a) in intron 3 disrupted the gene by
      formation of a truncated mRNA that lacked the coding sequence for the KRAB
      (Kruppel-associated box) and Znf-C2H2 domains of Zfp69, whereas the diabetogenic
      SJL, NON, and NZB alleles generated a normal mRNA. When combined with the B6.V
      Lep(ob) background, the diabetogenic Zfp69(SJL) allele produced hyperglycaemia,
      reduced gonadal fat, and increased plasma and liver triglycerides. mRNA levels of
      the human orthologue of Zfp69, ZNF642, were significantly increased in adipose
      tissue from patients with type 2 diabetes. We conclude that Zfp69 is the most
      likely candidate for the diabetogenic effect of Nidd/SJL, and that
      retrotransposon IAPLTR1a contributes substantially to the genetic heterogeneity
      of mouse strains. Expression of the transcription factor in adipose tissue may
      play a role in the pathogenesis of type 2 diabetes.

PMID- 19578399
TI  - Interactions between cells with distinct mutations in c-MYC and Pten in prostate
      cancer.
AB  - In human somatic tumorigenesis, mutations are thought to arise sporadically in
      individual cells surrounded by unaffected cells. This contrasts with most current
      transgenic models where mutations are induced synchronously in entire cell
      populations. Here we have modeled sporadic oncogene activation using a transgenic
      mouse in which c-MYC is focally activated in prostate luminal epithelial cells.
      Focal c-MYC expression resulted in mild pathology, but prostate-specific deletion
      of a single allele of the Pten tumor suppressor gene cooperated with c-MYC to
      induce high grade prostatic intraepithelial neoplasia (HGPIN)/cancer lesions.
      These lesions were in all cases associated with loss of Pten protein expression
      from the wild type allele. In the prostates of mice with concurrent homozygous
      deletion of Pten and focal c-MYC activation, double mutant (i.e. c-MYC+;Pten
      null) cells were of higher grade and proliferated faster than single mutant (Pten
      null) cells within the same glands. Consequently, double mutant cells outcompeted
      single mutant cells despite the presence of increased rates of apoptosis in the
      former. The p53 pathway was activated in Pten-deficient prostate cells and
      tissues, but c-MYC expression shifted the p53 response from senescence to
      apoptosis by repressing the p53 target gene p21(Cip1). We conclude that c-MYC
      overexpression and Pten deficiency cooperate to promote prostate tumorigenesis,
      but a p53-dependent apoptotic response may present a barrier to further
      progression. Our results highlight the utility of inducing mutations focally to
      model the competitive interactions between cell populations with distinct genetic
      alterations during tumorigenesis.

PMID- 19578400
TI  - Mitochondrial 2,4-dienoyl-CoA reductase deficiency in mice results in severe
      hypoglycemia with stress intolerance and unimpaired ketogenesis.
AB  - The mitochondrial beta-oxidation system is one of the central metabolic pathways
      of energy metabolism in mammals. Enzyme defects in this pathway cause fatty acid
      oxidation disorders. To elucidate the role of 2,4-dienoyl-CoA reductase (DECR) as
      an auxiliary enzyme in the mitochondrial beta-oxidation of unsaturated fatty
      acids, we created a DECR-deficient mouse line. In Decr(-/-) mice, the
      mitochondrial beta-oxidation of unsaturated fatty acids with double bonds is
      expected to halt at the level of trans-2, cis/trans-4-dienoyl-CoA intermediates.
      In line with this expectation, fasted Decr(-/-) mice displayed increased serum
      acylcarnitines, especially decadienoylcarnitine, a product of the incomplete
      oxidation of linoleic acid (C(18:2)), urinary excretion of unsaturated
      dicarboxylic acids, and hepatic steatosis, wherein unsaturated fatty acids
      accumulate in liver triacylglycerols. Metabolically challenged Decr(-/-) mice
      turned on ketogenesis, but unexpectedly developed hypoglycemia. Induced
      expression of peroxisomal beta-oxidation and microsomal omega-oxidation enzymes
      reflect the increased lipid load, whereas reduced mRNA levels of PGC-1alpha and
      CREB, as well as enzymes in the gluconeogenetic pathway, can contribute to stress
      induced hypoglycemia. Furthermore, the thermogenic response was perturbed, as
      demonstrated by intolerance to acute cold exposure. This study highlights the
      necessity of DECR and the breakdown of unsaturated fatty acids in the transition
      of intermediary metabolism from the fed to the fasted state.

PMID- 19578401
TI  - Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal
      independent origins for embryonic and regeneration melanocytes.
AB  - Adult stem cells are responsible for maintaining and repairing tissues during the
      life of an organism. Tissue repair in humans, however, is limited compared to the
      regenerative capabilities of other vertebrates, such as the zebrafish (Danio
      rerio). An understanding of stem cell mechanisms, such as how they are
      established, their self-renewal properties, and their recruitment to produce new
      cells is therefore important for the application of regenerative medicine. We use
      larval melanocyte regeneration following treatment with the melanocytotoxic drug
      MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC) regulation. In
      this paper, we show that the receptor tyrosine kinase, erbb3b, is required for
      establishing the adult MSC responsible for regenerating the larval melanocyte
      population. Both the erbb3b mutant and wild-type fish treated with the ErbB
      inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate
      melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at
      different time points, we show that ErbB signaling is only required for
      regeneration prior to MoTP treatment and before 48 hours of development,
      consistent with a role in establishing MSCs. We then show that overexpression of
      kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs,
      resulting in overproliferation of melanocytes. Furthermore, kitla overexpression
      can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is
      required to promote the progression and specification of the MSC from a pre-MSC
      state. This study provides evidence that ErbB signaling is required for the
      establishment of adult MSCs during embryonic development. That this requirement
      is not shared with the embryonic melanocytes suggests that embryonic melanocytes
      develop directly, without proceeding through the ErbB-dependent MSC. Moreover,
      the shared requirement of larval melanocyte regeneration and metamorphic
      melanocytes that develops at the larval-to-adult transition suggests that these
      post-embryonic melanocytes develop from the same adult MSC population. Lastly,
      that kitla overexpression can recruit the MSC to develop excess melanocytes
      raises the possibility that Kit signaling may be involved in MSC recruitment
      during regeneration.

PMID- 19578402
TI  - Enhanced disease susceptibility 1 and salicylic acid act redundantly to regulate
      resistance gene-mediated signaling.
AB  - Resistance (R) protein-associated pathways are well known to participate in
      defense against a variety of microbial pathogens. Salicylic acid (SA) and its
      associated proteinaceous signaling components, including enhanced disease
      susceptibility 1 (EDS1), non-race-specific disease resistance 1 (NDR1),
      phytoalexin deficient 4 (PAD4), senescence associated gene 101 (SAG101), and
      EDS5, have been identified as components of resistance derived from many R
      proteins. Here, we show that EDS1 and SA fulfill redundant functions in defense
      signaling mediated by R proteins, which were thought to function independent of
      EDS1 and/or SA. Simultaneous mutations in EDS1 and the SA-synthesizing enzyme
      SID2 compromised hypersensitive response and/or resistance mediated by R proteins
      that contain coiled coil domains at their N-terminal ends. Furthermore, the
      expression of R genes and the associated defense signaling induced in response to
      a reduction in the level of oleic acid were also suppressed by compromising SA
      biosynthesis in the eds1 mutant background. The functional redundancy with SA was
      specific to EDS1. Results presented here redefine our understanding of the roles
      of EDS1 and SA in plant defense.

PMID- 19578403
TI  - Run-off replication of host-adaptability genes is associated with gene transfer
      agents in the genome of mouse-infecting Bartonella grahamii.
AB  - The genus Bartonella comprises facultative intracellular bacteria adapted to
      mammals, including previously recognized and emerging human pathogens. We report
      the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most
      prevalent Bartonella species in wild rodents. Comparative genomics revealed that
      rodent-associated Bartonella species have higher copy numbers of genes for
      putative host-adaptability factors than the related human-specific pathogens.
      Many of these gene clusters are located in a highly dynamic region of 461 kb.
      Using hybridization to a microarray designed for the B. grahamii genome, we
      observed a massive, putatively phage-derived run-off replication of this region.
      We also identified a novel gene transfer agent, which packages the bacterial
      genome, with an over-representation of the amplified DNA, in 14 kb pieces. This
      is the first observation associating the products of run-off replication with a
      gene transfer agent. Because of the high concentration of gene clusters for host
      adaptation proteins in the amplified region, and since the genes encoding the
      gene transfer agent and the phage origin are well conserved in Bartonella, we
      hypothesize that these systems are driven by selection. We propose that the
      coupling of run-off replication with gene transfer agents promotes
      diversification and rapid spread of host-adaptability factors, facilitating host
      shifts in Bartonella.

PMID- 19578404
TI  - A targeted constitutive mutation in the APC tumor suppressor gene underlies
      mammary but not intestinal tumorigenesis.
AB  - Germline mutations in the adenomatous polyposis coli (APC) gene are responsible
      for familial adenomatous polyposis (FAP), an autosomal dominant hereditary
      predisposition to the development of multiple colorectal adenomas and of a broad
      spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate
      limiting and initiating role in the majority of sporadic colorectal cancers.
      Notwithstanding its multifunctional nature, the main tumor suppressing activity
      of the APC gene resides in its ability to regulate Wnt/beta-catenin signaling.
      Notably, genotype-phenotype correlations have been established at the APC gene
      between the length and stability of the truncated proteins encoded by different
      mutant alleles, the corresponding levels of Wnt/beta-catenin signaling activity
      they encode for, and the incidence and distribution of intestinal and extra
      intestinal tumors. Here, we report a novel mouse model, Apc1572T, obtained by
      targeting a truncated mutation at codon 1572 in the endogenous Apc gene. This
      hypomorphic mutant allele results in intermediate levels of Wnt/beta-catenin
      signaling activation when compared with other Apc mutations associated with
      multifocal intestinal tumors. Notwithstanding the constitutive nature of the
      mutation, Apc(+/1572T) mice have no predisposition to intestinal cancer but
      develop multifocal mammary adenocarcinomas and subsequent pulmonary metastases in
      both genders. The histology of the Apc1572T primary mammary tumours is highly
      heterogeneous with luminal, myoepithelial, and squamous lineages and is
      reminiscent of metaplastic carcinoma of the breast in humans. The striking
      phenotype of Apc(+/1572T) mice suggests that specific dosages of Wnt/beta-catenin
      signaling activity differentially affect tissue homeostasis and initiate
      tumorigenesis in an organ-specific fashion.

PMID- 19578405
TI  - Clustering of codons with rare cognate tRNAs in human genes suggests an extra
      level of expression regulation.
AB  - In species with large effective population sizes, highly expressed genes tend to
      be encoded by codons with highly abundant cognate tRNAs to maximize translation
      rate. However, there has been little evidence for a similar bias of synonymous
      codons in highly expressed human genes. Here, we ask instead whether there is
      evidence for the selection for codons associated with low abundance tRNAs. Rather
      than averaging the codon usage of complete genes, we scan the genes for windows
      with deviating codon usage. We show that there is a significant over
      representation of human genes that contain clusters of codons with low abundance
      cognate tRNAs. We name these regions, which on average have a 50% reduction in
      the amount of cognate tRNA available compared to the remainder of the gene, RTS
      (rare tRNA score) clusters. We observed a significant reduction in the
      substitution rate between the human RTS clusters and their orthologous chimp
      sequence, when compared to non-RTS cluster sequences. Overall, the genes with an
      RTS cluster have higher tissue specificity than the non-RTS cluster genes.
      Furthermore, these genes are functionally enriched for transcription regulation.
      As genes that regulate transcription in lower eukaryotes are known to be involved
      in translation on demand, this suggests that the mechanism of translation level
      expression regulation also exists within the human genome.

PMID- 19578406
TI  - Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a whole
      genome duplication.
AB  - Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life
      threatening infection characterized by rapid angioinvasive growth with an overall
      mortality rate that exceeds 50%. As a representative of the paraphyletic basal
      group of the fungal kingdom called "zygomycetes," R. oryzae is also used as a
      model to study fungal evolution. Here we report the genome sequence of R. oryzae
      strain 99-880, isolated from a fatal case of mucormycosis. The highly repetitive
      45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising
      approximately 20% of the genome. We predicted 13,895 protein-coding genes not
      overlapping TEs, many of which are paralogous gene pairs. The order and genomic
      arrangement of the duplicated gene pairs and their common phylogenetic origin
      provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD
      resulted in the duplication of nearly all subunits of the protein complexes
      associated with respiratory electron transport chains, the V-ATPase, and the
      ubiquitin-proteasome systems. The WGD, together with recent gene duplications,
      resulted in the expansion of multiple gene families related to cell growth and
      signal transduction, as well as secreted aspartic protease and subtilase protein
      families, which are known fungal virulence factors. The duplication of the
      ergosterol biosynthetic pathway, especially the major azole target, lanosterol
      14alpha-demethylase (ERG11), could contribute to the variable responses of R.
      oryzae to different azole drugs, including voriconazole and posaconazole.
      Expanded families of cell-wall synthesis enzymes, essential for fungal cell
      integrity but absent in mammalian hosts, reveal potential targets for novel and
      R. oryzae-specific diagnostic and therapeutic treatments.

PMID- 19578407
TI  - The genomics of speciation in Drosophila: diversity, divergence, and
      introgression estimated using low-coverage genome sequencing.
AB  - In nature, closely related species may hybridize while still retaining their
      distinctive identities. Chromosomal regions that experience reduced recombination
      in hybrids, such as within inversions, have been hypothesized to contribute to
      the maintenance of species integrity. Here, we examine genomic sequences from
      closely related fruit fly taxa of the Drosophila pseudoobscura subgroup to
      reconstruct their evolutionary histories and past patterns of genic exchange.
      Partial genomic assemblies were generated from two subspecies of Drosophila
      pseudoobscura (D. ps.) and an outgroup species, D. miranda. These new assemblies
      were compared to available assemblies of D. ps. pseudoobscura and D. persimilis,
      two species with overlapping ranges in western North America. Within inverted
      regions, nucleotide divergence among each pair of the three species is
      comparable, whereas divergence between D. ps. pseudoobscura and D. persimilis in
      non-inverted regions is much lower and closer to levels of intraspecific
      variation. Using molecular markers flanking each of the major chromosomal
      inversions, we identify strong crossover suppression in F(1) hybrids extending
      over 2 megabase pairs (Mbp) beyond the inversion breakpoints. These regions of
      crossover suppression also exhibit the high nucleotide divergence associated with
      inverted regions. Finally, by comparison to a geographically isolated subspecies,
      D. ps. bogotana, our results suggest that autosomal gene exchange between the
      North American species, D. ps. pseudoobscura and D. persimilis, occurred since
      the split of the subspecies, likely within the last 200,000 years. We conclude
      that chromosomal rearrangements have been vital to the ongoing persistence of
      these species despite recent hybridization. Our study serves as a proof-of
      principle on how whole genome sequencing can be applied to formulate and test
      hypotheses about species formation in lesser-known non-model systems.

PMID- 19578408
TI  - Risk Factors and Event Rates in Patients With Atherothrombotic Disease in
      Germany: Results of the REACH Registry.
AB  - INTRODUCTION: The aim of the international Reduction of Atherothrombosis for
      Continued Health (REACH) registry was to identify prospectively characteristics,
      risk factors, treatments, and cardiovascular event rates in stable outpatients
      with atherothrombotic disease, as well as in asymptomatic patients with risk
      factors for atherothrombotic disease. METHODS: A total of 512 physicians in
      Germany enrolled 4986 outpatients with documented atherothrombotic disease, as
      well as 608 asymptomatic patients with at least three risk factors for
      atherothrombotic disease, in the REACH registry. Patients will be followed for up
      to four years, with assessments being performed at regular intervals; the results
      of the one-year follow-up are presented here. RESULTS: The documented risk
      factors were hypertension (58.2%), hypercholesterolemia (74.6%), diabetes
      (37.6%), and obesity (28.1%). A large percentage of patients did not reach the
      therapeutic target values specified in current German and European S1 guidelines.
      After 1 year, 2.1% of the patients with symptomatic atherothrombotic disease and
      1.5% of the patients with at least three cardiovascular risk factors had died of
      a cardiovascular event, whereas 5.8% of the former and 2.5% of the latter patient
      group had reached a combined endpoint consisting of cardiovascular death,
      nonfatal myocardial infarction, and nonfatal stroke. CONCLUSION: The traditional
      risk factors are common in patients with coronary heart disease, cerebrovascular
      disease (stroke and/or transient ischemic attack), or peripheral arterial
      occlusive disease. Many patients with these conditions or associated risk factors
      are not treated according to current guidelines. This may explain, at least in
      part, the high rates of cardiovascular events observed after one year.

PMID- 19578409
TI  - Posterior tarsal tunnel syndrome: diagnosis and treatment.
AB  - BACKGROUND: Posterior tarsal tunnel syndrome is an uncommon clinical entity which
      is sometimes misdiagnosed in patients with pain of the retromalleolar region and
      the plantar aspect of the foot. Surgical intervention is recommended for
      correctly diagnosed posterior tarsal tunnel syndrome. METHODS: Selective
      literature review. RESULTS: Surgical treatment is indicated in the presence of
      dysesthesias refractory to conservative treatment or of neurological deficits. If
      a neural tumor or tarsal tunnel ganglion is suspected, diagnostic imaging (MRI,
      neurosonography) should precede surgery. Division of the flexor retinaculum
      (ligamentum laciniatum) in the tarsal tunnel must always include distal
      decompression of the end branches of the tibial nerve posterior to the fascia of
      the abductor hallucis muscle. Only extensive exposure of the nerve guarantees
      adequate release. CONCLUSION: Accurate diagnosis requires the evaluation of
      relevant clinical, neurological, and neurophysiological findings along with the
      careful consideration of other possible diagnoses. High success rates of 44% to
      91% are reported after operative treatment. The results are better in idiopathic
      than in posttraumatic cases. If surgery fails, re-operation is indicated only in
      patients with inadequate release.

PMID- 19578410
TI  - Treatment of depressive disorders.
AB  - INTRODUCTION: A confusing variety of options are available for the treatment of
      depressive disorders. METHOD: Selective literature review under consideration of
      current guidelines. RESULTS: The treatment of depression can be divided into
      acute, maintenance and prophylactic phases. The basic forms of treatment are
      pharmacotherapy, psychotherapy, and supportive strategies. The approximately 30
      antidepressants currently on the market differ mainly with respect to their side
      effect profiles. Of the specific types of psychotherapy, cognitive behavioral
      therapy, psychodynamic therapy, and psychoanalysis are funded by the statutory
      health insurance providers in Germany. All treatment strategies (except for sleep
      deprivation) show a latency of onset of several weeks and a nonresponse rate of
      about 30% to 50%. In clinical practice it is essential to follow a stepwise
      procedure and to perform a standardized evaluation of response after the latency
      period. In the event of nonresponse, the next step of treatment should be
      initiated. DISCUSSION: Depressive disorders have a good prognosis provided one
      takes best advantage of the available treatment options. Preconditions are
      continuation of treatment for an appropriate length of time (for antidepressants
      ca. 4 to 6 weeks, for psychotherapy ca. 4 to 12 weeks) and standardized
      evaluation of response thereafter.

PMID- 19578411
TI  - Sleep disorders in children beginning school: their causes and effects.
AB  - BACKGROUND: Sleep disorders are a common problem among children beginning school
      and may be associated both with impaired school performance and with behavioral
      difficulties. Because these disorders manifest themselves highly variably among
      children of any given age, and even in an individual affected child, they need an
      appropriate diagnostic evaluation so that the many environmental and background
      factors that may be relevant to the further course of the problem can be
      assessed. METHODS: Extensive data were obtained on approximately 1400 children
      who were tested before beginning school in 2005 by means of a special sleep
      questionnaire and another screening instrument that is used to assess behavioral
      strengths and difficulties (the SDQ, Strengths and Difficulties Questionnaire).
      RESULTS: Five percent of the children were found to have difficulty falling
      asleep, difficulty staying asleep, or nocturnal awakening. Less frequent problems
      included parasomnias such as pavor nocturnus (0.5%), sleepwalking (0.1%), and
      frequent nightmares (1.7%). CONCLUSION: Sleep disorders increase the risk of
      daytime fatigue and of psychological problems in general, including both
      hyperactivity and excessive emotional stress. These results imply that sleep
      problems and emotional disturbances are intimately connected and underscore the
      importance of diagnosing sleep problems in young children.

PMID- 19578412
TI  - Reconstructive oral and maxillofacial surgery.
AB  - BACKGROUND: The incidence of malignancies in the head and neck region is rising.
      Head and neck tumors are the eighth most frequent type of malignancy in German
      men, forming 3.3% of the total. As a result, the demand for functionally
      successful and esthetically pleasing reconstructions has increased. METHODS:
      Review based on a selective analysis of the pertinent literature and the
      guidelines of the German Association of Oral and Maxillofacial Surgery as well as
      the authors' clinical and scientific experience. RESULTS: Microsurgical flap
      transfer has become the most important type of reconstruction, with a more than
      90% rate of success, i.e., complete integration of the transplant in the
      recipient site. The most frequent complications are thromboses of the vein or
      artery of the pedicle. For each specific defect constellation, the most
      appropriate donor sites have been identified. Some donor sites are used for more
      than one defect. The principal risk factors for flap loss are prior operations on
      the neck, atherosclerosis, and previous radiation treatment. New developments
      include the use of perforator flaps, which can be anastomosed to very small
      vessels in the face, and wrist-carriers, which offer complete independence from
      head and neck vessels. CONCLUSION: The treatment, rehabilitation, and follow-up
      care of patients with tumors of the head and neck must be carried out by an
      interdisciplinary team. Full awareness of the available options for
      reconstruction helps the radiation therapist, oncologist, psychooncologist,
      general practitioner, and dentist to coordinate their efforts and advise their
      often mutilated and sometimes suicidal patients effectively.

PMID- 19578413
TI  - Correspondence (reply): In Reply.

PMID- 19578414
TI  - Correspondence (letter to the editor): Effective Measure.

PMID- 19578415
TI  - Correspondence (letter to the editor): Interdisciplinary Diagnostic System.

PMID- 19578416
TI  - Correspondence (letter to the editor): Inappropriate Simplification.

PMID- 19578417
TI  - Correspondence (reply): In Reply.

PMID- 19578418
TI  - Correspondence (letter to the editor): Special Motivation.

PMID- 19578419
TI  - Overweight, obesity and high waist circumference: regional differences in
      prevalence in primary medical care.
AB  - INTRODUCTION: The prevalence of obesity and elevated waist circumference in
      Germany is high. However, there are insufficient data on the situation in primary
      care and on regional distribution to support medical preventive measures.
      METHODS: The German Metabolic and Cardiovascular Risk Project (GEMCAS) is a
      national cross-sectional study including 1511 primary care practices and 35 869
      patients. Height, weight, waist circumference, laboratory values, and type 2
      diabetes were documented. RESULTS: The crude prevalence of obesity was 23.9% (95%
      CI 23.4 to 24.3) (standardized 22.8% [95% CI 22.3 to 23.2]), with a minimum in
      Bremen (19.8% [95% CI 15.1 to 24.5]) and a maximum in Saxony-Anhalt (28.3% [95%
      CI 25.4 to 31.1]). The crude prevalence of high waist circumference (> 102/88 cm)
      was 39.5% (95% CI 39.0 to 40.0) (standardized 36.5% [95% CI 36.0 to 36.9]), with
      a minimum in Hamburg (30.5% [95% CI 26.2 to 34.8]) and a maximum in Saxony-Anhalt
      (42.1% [95% CI 39.2 to 45.1]). The prevalence of obesity as assessed by BMI was
      higher in men than in women, but greater in women as assessed by waist
      circumference. Nationwide, 50 out of every 100 patients with obesity had type 2
      diabetes, and 32 of 100 patients with a high waist circumference had type 2
      diabetes. CONCLUSIONS: The prevalence of obesity is higher in northeastern
      Germany than in the southwest. Overall, abdominal obesity is considerably more
      frequent than obesity based on BMI. Surprisingly, a high prevalence of obesity in
      some federal states does not automatically mean a higher number of people with
      type 2 diabetes.

PMID- 19578421
TI  - Correspondence (letter to the editor): Common Constellation.

PMID- 19578420
TI  - Gender identity disorders in childhood and adolescence: currently debated
      concepts and treatment strategies.
AB  - INTRODUCTION: Gender identity disorders (GID) can appear even in early infancy
      with a variable degree of severity. Their prevalence in childhood and adolescence
      is below 1%. GID are often associated with emotional and behavioral problems as
      well as a high rate of psychiatric comorbidity. Their clinical course is highly
      variable. There is controversy at present over theoretical explanations of the
      causes of GID and over treatment approaches, particularly with respect to early
      hormonal intervention strategies. METHODS: This review is based on a selective
      Medline literature search, existing national and international guidelines, and
      the results of a discussion among experts from multiple relevant disciplines.
      RESULTS: As there have been no large studies to date on the course of GID, and,
      in particular, no studies focusing on causal factors for GID, the evidence level
      for the various etiological models that have been proposed is generally low. Most
      models of these disorders assume that they result from a complex biopsychosocial
      interaction. Only 2.5% to 20% of all cases of GID in childhood and adolescence
      are the initial manifestation of irreversible transsexualism. The current state
      of research on this subject does not allow any valid diagnostic parameters to be
      identified with which one could reliably predict whether the manifestations of
      GID will persist, i.e., whether transsexualism will develop with certainty or, at
      least, a high degree of probability. CONCLUSIONS: The types of modulating
      influences that are known from the fields of developmental psychology and family
      dynamics have therapeutic implications for GID. As children with GID only rarely
      go on to have permanent transsexualism, irreversible physical interventions are
      clearly not indicated until after the individual's psychosexual development ist
      complete. The identity-creating experiences of this phase of development should
      not be restricted by the use of LHRH analogues that prevent puberty.

PMID- 19578423
TI  - Correspondence (reply): In Reply.

PMID- 19578422
TI  - Correspondence (reply): In Reply.

PMID- 19578424
TI  - Correspondence (letter to the editor): End Points insufficiently Evaluated.

PMID- 19578425
TI  - Correspondence (reply): In Reply.

PMID- 19578426
TI  - Correspondence (letter to the editor): Blunt Projections.

PMID- 19578427
TI  - Investigating the conformational stability of prion strains through a kinetic
      replication model.
AB  - Prion proteins are known to misfold into a range of different aggregated forms,
      showing different phenotypic and pathological states. Understanding strain
      specificities is an important problem in the field of prion disease. Little is
      known about which PrP(Sc) structural properties and molecular mechanisms
      determine prion replication, disease progression and strain phenotype. The aim of
      this work is to investigate, through a mathematical model, how the structural
      stability of different aggregated forms can influence the kinetics of prion
      replication. The model-based results suggest that prion strains with different
      conformational stability undergoing in vivo replication are characterizable in
      primis by means of different rates of breakage. A further role seems to be played
      by the aggregation rate (i.e. the rate at which a prion fibril grows). The
      kinetic variability introduced in the model by these two parameters allows us to
      reproduce the different characteristic features of the various strains (e.g.,
      fibrils' mean length) and is coherent with all experimental observations
      concerning strain-specific behavior.

PMID- 19578428
TI  - Drug discovery using chemical systems biology: repositioning the safe medicine
      Comtan to treat multi-drug and extensively drug resistant tuberculosis.
AB  - The rise of multi-drug resistant (MDR) and extensively drug resistant (XDR)
      tuberculosis around the world, including in industrialized nations, poses a great
      threat to human health and defines a need to develop new, effective and
      inexpensive anti-tubercular agents. Previously we developed a chemical systems
      biology approach to identify off-targets of major pharmaceuticals on a proteome
      wide scale. In this paper we further demonstrate the value of this approach
      through the discovery that existing commercially available drugs, prescribed for
      the treatment of Parkinson's disease, have the potential to treat MDR and XDR
      tuberculosis. These drugs, entacapone and tolcapone, are predicted to bind to the
      enzyme InhA and directly inhibit substrate binding. The prediction is validated
      by in vitro and InhA kinetic assays using tablets of Comtan, whose active
      component is entacapone. The minimal inhibition concentration (MIC(99)) of
      entacapone for Mycobacterium tuberculosis (M.tuberculosis) is approximately 260.0
      microM, well below the toxicity concentration determined by an in vitro
      cytotoxicity model using a human neuroblastoma cell line. Moreover, kinetic
      assays indicate that Comtan inhibits InhA activity by 47.0% at an entacapone
      concentration of approximately 80 microM. Thus the active component in Comtan
      represents a promising lead compound for developing a new class of anti
      tubercular therapeutics with excellent safety profiles. More generally, the
      protocol described in this paper can be included in a drug discovery pipeline in
      an effort to discover novel drug leads with desired safety profiles, and
      therefore accelerate the development of new drugs.

PMID- 19578429
TI  - A compact representation of drawing movements with sequences of parabolic
      primitives.
AB  - Some studies suggest that complex arm movements in humans and monkeys may
      optimize several objective functions, while others claim that arm movements
      satisfy geometric constraints and are composed of elementary components. However,
      the ability to unify different constraints has remained an open question. The
      criterion for a maximally smooth (minimizing jerk) motion is satisfied for
      parabolic trajectories having constant equi-affine speed, which thus comply with
      the geometric constraint known as the two-thirds power law. Here we empirically
      test the hypothesis that parabolic segments provide a compact representation of
      spontaneous drawing movements. Monkey scribblings performed during a period of
      practice were recorded. Practiced hand paths could be approximated well by
      relatively long parabolic segments. Following practice, the orientations and
      spatial locations of the fitted parabolic segments could be drawn from only 2-4
      clusters, and there was less discrepancy between the fitted parabolic segments
      and the executed paths. This enabled us to show that well-practiced spontaneous
      scribbling movements can be represented as sequences ("words") of a small number
      of elementary parabolic primitives ("letters"). A movement primitive can be
      defined as a movement entity that cannot be intentionally stopped before its
      completion. We found that in a well-trained monkey a movement was usually
      decelerated after receiving a reward, but it stopped only after the completion of
      a sequence composed of several parabolic segments. Piece-wise parabolic segments
      can be generated by applying affine geometric transformations to a single
      parabolic template. Thus, complex movements might be constructed by applying
      sequences of suitable geometric transformations to a few templates. Our findings
      therefore suggest that the motor system aims at achieving more parsimonious
      internal representations through practice, that parabolas serve as geometric
      primitives and that non-Euclidean variables are employed in internal movement
      representations (due to the special role of parabolas in equi-affine geometry).

PMID- 19578430
TI  - What a plant sounds like: the statistics of vegetation echoes as received by
      echolocating bats.
AB  - A critical step on the way to understanding a sensory system is the analysis of
      the input it receives. In this work we examine the statistics of natural complex
      echoes, focusing on vegetation echoes. Vegetation echoes constitute a major part
      of the sensory world of more than 800 species of echolocating bats and play an
      important role in several of their daily tasks. Our statistical analysis is based
      on a large collection of plant echoes acquired by a biomimetic sonar system. We
      explore the relation between the physical world (the structure of the plant) and
      the characteristics of its echo. Finally, we complete the story by analyzing the
      effect of the sensory processing of both the echolocation and the auditory
      systems on the echoes and interpret them in the light of information
      maximization. The echoes of all different plant species we examined share a
      surprisingly robust pattern that was also reproduced by a simple Poisson model of
      the spatial reflector arrangement. The fine differences observed between the
      echoes of different plant species can be explained by the spatial characteristics
      of the plants. The bat's emitted signal enhances the most informative spatial
      frequency range where the species-specific information is large. The auditory
      system filtering affects the echoes in a similar way, thus enhancing the most
      informative spatial frequency range even more. These findings suggest how the
      bat's sensory system could have evolved to deal with complex natural echoes.

PMID- 19578431
TI  - The Gene Ontology's Reference Genome Project: a unified framework for functional
      annotation across species.
AB  - The Gene Ontology (GO) is a collaborative effort that provides structured
      vocabularies for annotating the molecular function, biological role, and cellular
      location of gene products in a highly systematic way and in a species-neutral
      manner with the aim of unifying the representation of gene function across
      different organisms. Each contributing member of the GO Consortium independently
      associates GO terms to gene products from the organism(s) they are annotating.
      Here we introduce the Reference Genome project, which brings together those
      independent efforts into a unified framework based on the evolutionary
      relationships between genes in these different organisms. The Reference Genome
      project has two primary goals: to increase the depth and breadth of annotations
      for genes in each of the organisms in the project, and to create data sets and
      tools that enable other genome annotation efforts to infer GO annotations for
      homologous genes in their organisms. In addition, the project has several
      important incidental benefits, such as increasing annotation consistency across
      genome databases, and providing important improvements to the GO's logical
      structure and biological content.

PMID- 19578432
TI  - Analysis of pools of targeted Salmonella deletion mutants identifies novel genes
      affecting fitness during competitive infection in mice.
AB  - Pools of mutants of minimal complexity but maximal coverage of genes of interest
      facilitate screening for genes under selection in a particular environment. We
      constructed individual deletion mutants in 1,023 Salmonella enterica serovar
      Typhimurium genes, including almost all genes found in Salmonella but not in
      related genera. All mutations were confirmed simultaneously using a novel
      amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter,
      introduced during the construction of each mutant, followed by hybridization of
      this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability
      to identify fitness phenotypes using our pool of mutants, the pool was subjected
      to selection by intraperitoneal injection into BALB/c mice and subsequent
      recovery from spleens. Changes in the representation of each mutant were
      monitored using T7 transcripts hybridized to a novel inexpensive minimal
      microarray. Among the top 120 statistically significant spleen colonization
      phenotypes, more than 40 were mutations in genes with no previously known role in
      this model. Fifteen phenotypes were tested using individual mutants in
      competitive assays of intraperitoneal infection in mice and eleven were
      confirmed, including the first two examples of attenuation for sRNA mutants in
      Salmonella. We refer to the method as Array-based analysis of cistrons under
      selection (ABACUS).

PMID- 19578433
TI  - The dynamics of EBV shedding implicate a central role for epithelial cells in
      amplifying viral output.
AB  - To develop more detailed models of EBV persistence we have studied the dynamics
      of virus shedding in healthy carriers. We demonstrate that EBV shedding into
      saliva is continuous and rapid such that the virus level is replaced in < or =2
      minutes, the average time that a normal individual swallows. Thus, the mouth is
      not a reservoir of virus but a conduit through which a continuous flow stream of
      virus passes in saliva. Consequently, virus is being shed at a much higher rate
      than previously thought, a level too high to be accounted for by replication in B
      cells in Waldeyer's ring alone. Virus shedding is relatively stable over short
      periods (hours-days) but varies through 3.5 to 5.5 logs over longer periods, a
      degree of variation that also cannot be accounted for solely by replication in B
      cells. This variation means, contrary to what is generally believed, that the
      definition of high and low shedder is not so much a function of variation between
      individuals but within individuals over time. The dynamics of shedding describe a
      process governing virus production that is occurring independently < or =3 times
      at any moment. This process grows exponentially and is then randomly terminated.
      We propose that these dynamics are best explained by a model where single B cells
      sporadically release virus that infects anywhere from 1 to 5 epithelial cells.
      This infection spreads at a constant exponential rate and is terminated randomly,
      resulting in infected plaques of epithelial cells ranging in size from 1 to 10(5)
      cells. At any one time there are a very small number (< or =3) of plaques. We
      suggest that the final size of these plaques is a function of the rate of
      infectious spread within the lymphoepithelium which may be governed by the
      structural complexity of the tissue but is ultimately limited by the immune
      response.

PMID- 19578434
TI  - Evidence for a "wattle and daub" model of the cyst wall of entamoeba.
AB  - The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen
      Entamoeba histolytica, is composed of fibrils of chitin and three chitin-binding
      lectins called Jacob, Jessie3, and chitinase. Here we show chitin, which was
      detected with wheat germ agglutinin, is made in secretory vesicles prior to its
      deposition on the surface of encysting Ei. Jacob lectins, which have tandemly
      arrayed chitin-binding domains (CBDs), and chitinase, which has an N-terminal
      CBD, were each made early during encystation. These results are consistent with
      their hypothesized roles in cross-linking chitin fibrils (Jacob lectins) and
      remodeling the cyst wall (chitinase). Jessie3 lectins likely form the mortar or
      daub of the cyst wall, because 1) Jessie lectins were made late during
      encystation; 2) the addition to Jessie lectins to the cyst wall correlated with a
      marked decrease in the permeability of cysts to nucleic acid stains (DAPI) and
      actin-binding heptapeptide (phalloidin); and 3) recombinant Jessie lectins,
      expressed as a maltose-binding proteins in the periplasm of Escherichia coli,
      caused transformed bacteria to agglutinate in suspension and form a hard pellet
      that did not dissociate after centrifugation. Jessie3 appeared as linear forms
      and rosettes by negative staining of secreted recombinant proteins. These
      findings provide evidence for a "wattle and daub" model of the Entamoeba cyst
      wall, where the wattle or sticks (chitin fibrils likely cross-linked by Jacob
      lectins) is constructed prior to the addition of the mortar or daub (Jessie3
      lectins).

PMID- 19578435
TI  - NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to
      Mycobacterium tuberculosis.
AB  - While the recognition of microbial infection often occurs at the cell surface via
      Toll-like receptors, the cytosol of the cell is also under surveillance for
      microbial products that breach the cell membrane. An important outcome of
      cytosolic recognition is the induction of IFNalpha and IFNbeta, which are
      critical mediators of immunity against both bacteria and viruses. Like many
      intracellular pathogens, a significant fraction of the transcriptional response
      to Mycobacterium tuberculosis infection depends on these type I interferons, but
      the recognition pathways responsible remain elusive. In this work, we demonstrate
      that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that
      responds to bacterial peptidoglycan, and this event requires membrane damage that
      is actively inflicted by the bacterium. Unexpectedly, this recognition triggers
      the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This
      response is only partially impaired by the loss of Irf3 and therefore, differs
      fundamentally from those stimulated by bacterial DNA, which depend entirely on
      this transcription factor. This difference appears to result from the unusual
      peptidoglycan produced by mycobacteria, which we show is a uniquely potent
      agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to
      recognize bacteria that actively perturb host membranes and is remarkably
      sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure
      exerted by these pathogens on the mammalian immune system.

PMID- 19578436
TI  - Chemical genetics reveals bacterial and host cell functions critical for type IV
      effector translocation by Legionella pneumophila.
AB  - Delivery of effector proteins is a process widely used by bacterial pathogens to
      subvert host cell functions and cause disease. Effector delivery is achieved by
      elaborate injection devices and can often be triggered by environmental stimuli.
      However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system
      cannot be detected until the bacterium encounters a target host cell. We used
      chemical genetics, a perturbation strategy that utilizes small molecule
      inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot
      activity. From a collection of more than 2,500 annotated molecules we identified
      specific inhibitors of effector translocation. We found that L. pneumophila
      effector translocation in macrophages requires host cell factors known to be
      involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin.
      Moreover, we found that L. pneumophila phagocytosis and effector translocation
      also specifically require the receptor protein tyrosine phosphate phosphatases
      CD45 and CD148. We further show that phagocytosis is required to trigger effector
      delivery unless intimate contact between the bacteria and the host is
      artificially generated. In addition, real-time analysis of effector translocation
      suggests that effector export is rate-limited by phagocytosis. We propose a model
      in which L. pneumophila utilizes phagocytosis to initiate an intimate contact
      event required for the translocation of pre-synthesized effector molecules. We
      discuss the need for host cell participation in the initial step of the infection
      and its implications in the L. pneumophila lifestyle. Chemical genetic screening
      provides a novel approach to probe the host cell functions and factors involved
      in host-pathogen interactions.

PMID- 19578437
TI  - RNAi targeting of West Nile virus in mosquito midguts promotes virus
      diversification.
AB  - West Nile virus (WNV) exists in nature as a genetically diverse population of
      competing genomes. This high genetic diversity and concomitant adaptive
      plasticity has facilitated the rapid adaptation of WNV to North American
      transmission cycles and contributed to its explosive spread throughout the New
      World. WNV is maintained in nature in a transmission cycle between mosquitoes and
      birds, with intrahost genetic diversity highest in mosquitoes. The mechanistic
      basis for this increase in genetic diversity in mosquitoes is poorly understood.
      To determine whether the high mutational diversity of WNV in mosquitoes is driven
      by RNA interference (RNAi), we characterized the RNAi response to WNV in the
      midguts of orally exposed Culex pipiens quinquefasciatus using high-throughput,
      massively parallel sequencing and estimated viral genetic diversity. Our data
      demonstrate that WNV infection in orally exposed vector mosquitoes induces the
      RNAi pathway and that regions of the WNV genome that are more intensely targeted
      by RNAi are more likely to contain point mutations compared to weakly targeted
      regions. These results suggest that, under natural conditions, positive selection
      of WNV within mosquitoes is stronger in regions highly targeted by the host RNAi
      response. Further, they provide a mechanistic basis for the relative importance
      of mosquitoes in driving WNV diversification.

PMID- 19578438
TI  - Isolation and characterization of adenoviruses persistently shed from the
      gastrointestinal tract of non-human primates.
AB  - Adenoviruses are important human pathogens that have been developed as vectors
      for gene therapies and genetic vaccines. Previous studies indicated that human
      infections with adenoviruses are self-limiting in immunocompetent hosts with
      evidence of some persistence in adenoid tissue. We sought to better understand
      the natural history of adenovirus infections in various non-human primates and
      discovered that healthy populations of great apes (chimpanzees, bonobos,
      gorillas, and orangutans) and macaques shed substantial quantities of infectious
      adenoviruses in stool. Shedding in stools from asymptomatic humans was found to
      be much less frequent, comparable to frequencies reported before. We purified and
      fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from
      macaques. Analyses of the new ape adenovirus sequences (as well as the 4
      chimpanzee adenovirus sequences we have previously reported) together with 22
      complete adenovirus genomes available from GenBank revealed that (a) the ape
      adenoviruses could clearly be classified into species corresponding to human
      adenovirus species B, C, and E, (b) there was evidence for intraspecies
      recombination between adenoviruses, and (c) the high degree of phylogenetic
      relatedness of adenoviruses across their various primate hosts provided evidence
      for cross species transmission events to have occurred in the natural history of
      B and E viruses. The high degree of asymptomatic shedding of live adenovirus in
      non-human primates and evidence for zoonotic transmissions warrants caution for
      primate handling and housing. Furthermore, the presence of persistent and/or
      latent adenovirus infections in the gut should be considered in the design and
      interpretation of human and non-human primate studies with adenovirus vectors.

PMID- 19578439
TI  - The alphaGal epitope of the histo-blood group antigen family is a ligand for
      bovine norovirus Newbury2 expected to prevent cross-species transmission.
AB  - Among Caliciviridae, the norovirus genus encompasses enteric viruses that infect
      humans as well as several animal species, causing gastroenteritis. Porcine
      strains are classified together with human strains within genogroup II, whilst
      bovine norovirus strains represent genogroup III. Various GI and GII human
      strains bind to carbohydrates of the histo-blood group family which may be shared
      among mammalian species. Genetic relatedness of human and animal strains as well
      as the presence of potentially shared ligands raises the possibility of norovirus
      cross-species transmission. In the present study, we identified a carbohydrate
      ligand for the prototype bovine norovirus strain Bo/Newbury2/76/UK (NB2).
      Attachment of virus-like particles (VLPs) of the NB2 strain to bovine gut tissue
      sections showed a complete match with the staining by reagents recognizing the
      Galalpha1,3 motif. Alpha-galactosidase treatment confirmed involvement of a
      terminal alpha-linked galactose. Specific binding of VLPs to the alphaGal epitope
      (Galalpha3Galbeta4GlcNAcbeta-R) was observed. The binding of Galalpha3GalalphaOMe
      to rNB2 VLPs was characterized at atomic resolution employing saturation transfer
      difference (STD) NMR experiments. Transfection of human cells with an
      alpha1,3galactosyltransferase cDNA allowed binding of NB2 VLPs, whilst inversely,
      attachment to porcine vascular endothelial cells was lost when the cells
      originated from an alpha1,3galactosyltransferase KO animal. The alphaGal epitope
      is expressed in all mammalian species with the exception of the Hominidaea family
      due to the inactivation of the alpha1,3galactosyltransferase gene (GGTA1).
      Accordingly, the NB2 carbohydrate ligand is absent from human tissues. Although
      expressed on porcine vascular endothelial cells, we observed that unlike in cows,
      it is not present on gut epithelial cells, suggesting that neither man nor pig
      could be infected by the NB2 bovine strain.

PMID- 19578440
TI  - Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with
      Toxoplasma gondii.
AB  - To better understand the initiation of CD8(+) T cell responses during infection,
      the primary response to the intracellular parasite Toxoplasma gondii was
      characterized using 2-photon microscopy combined with an experimental system that
      allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T
      cells. Infection with T. gondii induced localization of both these populations to
      the sub-capsular/interfollicular region of the draining lymph node and DCs were
      required for the expansion of the T cells. Consistent with current models, in the
      presence of cognate antigen, the average velocity of CD8(+) T cells decreased.
      Unexpectedly, infection also resulted in modulation of the behavior of non
      parasite specific T cells. This TCR-independent process correlated with the re
      modeling of the lymph node micro-architecture and changes in expression of CCL21
      and CCL3. Infection also resulted in sustained interactions between the DCs and
      CD8(+) T cells that were visualized only in the presence of cognate antigen and
      were limited to an early phase in the response. Infected DCs were rare within the
      lymph node during this time frame; however, DCs presenting the cognate antigen
      were detected. Together, these data provide novel insights into the earliest
      interaction between DCs and CD8(+) T cells and suggest that cross presentation by
      bystander DCs rather than infected DCs is an important route of antigen
      presentation during toxoplasmosis.

PMID- 19578442
TI  - Sporting activity, prevalence of overweight, and risk factors: cross-sectional
      study of more than 12 500 participants aged 16 to 25 years.
AB  - BACKGROUND: Recent studies show that habits detrimental to health are becoming
      established ever earlier in life. Because most of these investigations focus on
      adolescents up to the age of 18 years, it is largely unknown whether and to what
      extent negative behavioral modifications are intensified in young adults.
      METHODS: Within the cross-sectional study "Fit furs Leben" (Fit for Life) 12 835
      volunteers aged 16 to 25 years were anthropometrically investigated and
      interviewed about their lifestyle and habits (sporting activity, nutrition and
      health-related behavior). RESULTS: Data on anthropometric (BMI, waist
      circumference, body fat) and health-relevant (lack of exercise, smoking)
      characteristics as well as the frequency of cardiovascular risk factors show a
      clear increase in unhealthy attributes, particularly among those aged 20 to 25
      years. Fifty percent of 25-year-old men are overweight, 60% smoke, and around one
      third do not participate in sport. Although only one quarter of women aged 16 to
      25 years are overweight, women engage in sport much less frequently. Only one
      quarter of all study participants display none of the investigated cardiovascular
      risk factors. DISCUSSION: The health-detrimental tendencies increase considerably
      after the age of 20. Efficient cross-institutional prevention campaigns are
      urgently necessary to promote and continually support a health-conscious life
      style.

PMID- 19578441
TI  - Differential gene expression patterns of EBV infected EBNA-3A positive and
      negative human B lymphocytes.
AB  - The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited
      set is expressed in EBV-growth transformed B cells, termed lymphoblastoid cell
      lines (LCLs). These cells proliferate via the concerted action of EBV nuclear
      antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate
      limiting to establish a stable homeostasis of growth promoting and anti-apoptotic
      activities. We show here that EBV mutants, which lack the EBNA-3A gene, are
      impaired but can still initiate cell cycle entry and proliferation of primary
      human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and
      in contrast to previous reports, these viral mutants are attenuated in growth
      transformation assays but give rise to permanently growing EBNA-3A negative B
      cell lines which exhibit reduced proliferation rates and elevated levels of
      apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129
      down-regulated and 167 up-regulated genes, which are significantly enriched for
      genes involved in apoptotic processes or cell cycle progression like the tumor
      suppressor gene p16/INK4A, or might contribute to essential steps of the viral
      life cycle in the infected host. In addition, EBNA-3A cellular target genes
      remarkably overlap with previously identified targets of EBNA-2. This study
      comprises the first genome wide expression profiles of EBNA-3A target genes
      generated within the complex network of viral proteins of the growth transformed
      B cell and permits a more detailed understanding of EBNA-3A's function and
      contribution to viral pathogenesis.

PMID- 19578443
TI  - Eosinophilia in returning travelers and migrants.
AB  - INTRODUCTION: Eosinophilia in travelers returning from tropical countries is
      often caused by helminths. The high eosinophil counts arise particularly from
      tissue migration of invasive larvae. METHODS: Review of literature selected by
      means of a Medline search using the MeSH terms "eosinophilia" and "helminth."
      RESULTS: The patient's geographic and alimentary history may suggest infection
      with particular parasitic worms. A targeted diagnostic approach is suggested. The
      physician should concentrate on the principal signs and be guided by the
      geographic and alimentary history. Elaborate diagnostic measures are seldom
      indicated. DISCUSSION: Although eosinophilia alone has low positive predictive
      value for a worm infection, it points clearly to helminthosis if the patient has
      recently returned from the tropics and the eosinophilia is new.

PMID- 19578444
TI  - Correspondence (reply): In Reply.

PMID- 19578445
TI  - Correspondence (letter to the editor): Pointed Comment.

PMID- 19578447
TI  - Assisted reproduction: an important review of the literature on the risk of
      malformation after in vitro fertilization and intracytoplasmic sperm injection.

PMID- 19578446
TI  - Cardiovascular risk factors and signs of subclinical atherosclerosis in the Heinz
      Nixdorf Recall Study.
AB  - INTRODUCTION: Modern investigation modalities allow markers of atherosclerosis to
      be detected at a subclinical stage. The aim of the study was to analyze the
      prevalence of these markers in relation to traditional risk factors. METHODS: The
      population based study included 4814 participants, aged 45 to 75 years, with a
      response rate of 55.8% of those contacted. The patients' history, psychosocial
      and environmental risk factors were assessed. RESULTS: The prevalence of obesity
      was 26.2% in men and 28.1% in women, 26% of men and 21% of women were smokers.
      Hypertension was found in 46% of men and 31% of women, diabetes in 9.3% of men
      and 6.3% of women. Markers of subclinical peripheral arterial disease were found
      in 6.4% of men and 5.1% of women, of subclinical carotid artery disease in 43.2%
      and 30.7%, and of subclinical coronary artery calcification in 82.3% and 55.2%,
      respectively. The prevalence of coronary calcification measured using an Agatston
      Score >100 was in 40% in men and 15% in women, using a score >400, 16.8% and
      4.5%, respectively. DISCUSSION: A high prevalence of subclinical atherosclerosis
      was found in the older population. The follow-up period will demonstrate whether
      the detection of markers of subclinical atherosclerosis will improve risk
      stratification beyond that offered by traditional risk factors.

PMID- 19578448
TI  - The risk of malformation following assisted reproduction.
AB  - INTRODUCTION: Intracytoplasmatic sperm injection (ICSI) is currently the most
      frequently used human reproductive technology in Germany. ICSI was introduced as
      routine, insurance-funded medical care in 2002 by the Federal Joint Committee. A
      re-evaluation of published literature on malformation rates in children born of
      ICSI pregnancies within a period of three years formed part of the committee's
      decision. The analysis investigated whether ICSI increases the risk of
      malformation in the offspring, compared to in vitro fertilization (IVF) and
      natural conception. METHODS: Systematic literature review. RESULTS: 929 studies
      were identified. Three meta-analyses, 15 studies investigating malformations, and
      12 studies analyzing imprinting disorders were included. The risk of malformation
      was not significantly different in nine studies comparing ICSI versus IVF. Two
      meta-analyses and three of eight cohort studies and retrospective analysis showed
      significantly more severe malformations after assisted reproduction than after
      natural conception. The remaining five studies displayed no significant results.
      Current evidence does not show a higher risk of major malformations in the
      offspring resulting from the use of ICSI compared to IVF. However, there is
      evidence that both techniques increase the risk for major malformations
      considerably, compared to natural conception, and further research is needed. The
      validity of the results is low since the studies were heterogeneous and the
      cohorts used in the studies had limited comparability.

PMID- 19578449
TI  - Complete caval thrombosis secondary to an implanted venous port--a case study.
AB  - HISTORY AND CLINICAL FINDINGS: We report the case of a woman who presented to the
      medical emergency room with upper thoracic inlet syndrome six months after being
      treated for cancer of the left breast with surgery, radiation, and chemotherapy.
      A port-related occlusion of the superior vena cava was diagnosed on the basis of
      the history, physical findings, and diagnostic images. METHODS: The local
      standards for the handling of port systems are presented. DISCUSSION: Implanted
      port systems facilitate the treatment of the chronically ill by enabling easy and
      safe venous access. As the number of patients with such systems is growing, there
      is an increased need for optimized handling and care, awareness of the risks
      (such as catheter occlusion, thrombosis, and infection), and recognition of
      complications when they arise.

PMID- 19578450
TI  - Reduction in cervical cancers proven?

PMID- 19578451
TI  - Low efficacy.

PMID- 19578452
TI  - Efficacy unproven.

PMID- 19578454
TI  - The cost debate.

PMID- 19578455
TI  - The treatment of deep vein thrombosis in the pelvis and leg.
AB  - INTRODUCTION: Deep vein thrombosis is associated with a risk of pulmonary
      embolism and post thrombotic syndrome (PTS). METHODS: Selective literature review
      with special reference to the American College of Chest Physicians' current
      guidelines and the German S2 interdisciplinary guideline. RESULTS AND DISCUSSION:
      The most important therapeutic measure is prompt and adequate anticoagulation
      with heparin or fondaparinux. Thrombolysis or thrombectomy is only indicated in
      highly selected severe cases. The risk of PTS can be reduced by immediate ongoing
      treatment with compression stockings. Prevention of relapse is achieved using
      vitamin K antagonists with a target INR of 2.0 to 3.0. The duration of
      anticoagulation should be tailored to the localisation and etiology of the
      thrombosis, from at least three months to indefinite treatment. The ongoing risk
      of bleeding secondary to anticoagulation should be reevaluated at regular
      intervals as a cost-benefit analysis. New anticoagulants for acute and long term
      treatment will soon be available for clinical use.

PMID- 19578456
TI  - Analysis of airborne betula pollen in Finland; a 31-year perspective.
AB  - In this 31-year retrospective study, we examined the influence of meteorology on
      airborne Betula spp. (birch) pollen concentrations in Turku, Finland. The
      seasonal incidence of airborne birch pollen in Turku occurred over a brief period
      each year during spring (April 30 - May 31). Mean peak concentrations were
      restricted to May (May 5 to 13). Statistically significant increases in the
      annual accumulated birch pollen sum and daily maximum values were observed over
      the study period. Birch pollen counts collected in April were retrospectively
      shown to increase over the duration of the study. Increases in April temperature
      values were also significantly associated with the earlier onset of the birch
      pollen season. Furthermore, the number of days where daily birch pollen
      concentrations exceeded 10 and 1,000 grains/m(3) also increased throughout the
      study period. These data demonstrate that increases in temperature, especially
      during months preceding the onset of the birch pollen season, favor preseason
      phenological development and pollen dispersal. Birch pollen derived from other
      geographical locations may also contribute to the aerospora of Turku, Finland. To
      date, the public health burden associated with personal exposure to elevated
      birch pollen loads remains unclear and is the focus of future epidemiological
      research.

PMID- 19578457
TI  - The built environment and health: introducing individual space-time behavior.
AB  - Many studies have examined the relationship between the built environment and
      health. Yet, the question of how and why the environment influences health
      behavior remains largely unexplored. As health promotion interventions work
      through the individuals in a targeted population, an explicit understanding of
      individual behavior is required to formulate and evaluate intervention
      strategies. Bringing in concepts from various fields, this paper proposes the use
      of an activity-based modeling approach for understanding and predicting, from the
      bottom up, how individuals interact with their environment and each other in
      space and time, and how their behaviors aggregate to population-level health
      outcomes.

PMID- 19578458
TI  - Calibrating self-reported measures of maternal smoking in pregnancy via bioassays
      using a Monte Carlo approach.
AB  - Maternal smoking during pregnancy is a major public health problem that has been
      associated with numerous short- and long-term adverse health outcomes in
      offspring. However, characterizing smoking exposure during pregnancy precisely
      has been rather difficult: self-reported measures of smoking often suffer from
      recall bias, deliberate misreporting, and selective non-disclosure, while single
      bioassay measures of nicotine metabolites only reflect recent smoking history and
      cannot capture the fluctuating and complex patterns of varying exposure of the
      fetus. Recently, Dukic et al. have proposed a statistical method for combining
      information from both sources in order to increase the precision of the exposure
      measurement and power to detect more subtle effects of smoking. In this paper, we
      extend the Dukic et al. method to incorporate individual variation of the
      metabolic parameters (such as clearance rates) into the calibration model of
      smoking exposure during pregnancy. We apply the new method to the Family Health
      and Development Project (FHDP), a small convenience sample of 96 predominantly
      working class white pregnant women oversampled for smoking. We find that, on
      average, misreporters smoke 7.5 cigarettes more than what they report to smoke,
      with about one third underreporting by 1.5, one third under-reporting by about
      6.5, and one third underreporting by 8.5 cigarettes. Partly due to the limited
      demographic heterogeneity in the FHDP sample, the results are similar to those
      obtained by the deterministic calibration model, whose adjustments were slightly
      lower (by 0.5 cigarettes on average). The new results are also, as expected, less
      sensitive to assumed values of cotinine half-life.

PMID- 19578459
TI  - Hazards faced by young designated drivers: in-car risks of driving drunken
      passengers.
AB  - This qualitative study explored the risk in the practice of young designated
      drivers transporting drunken peers. Young drivers 18-29 years old in Alberta,
      Canada participated in 12 focus groups (N = 146). Interviews were semi
      structured. A key finding is that when highly intoxicated youth are driven by a
      designated driver who is a peer, they are likely to behave in ways that are
      unsafe. Unsafe actions of drunken passengers in the vehicle include physical
      "rough-housing" with the driver, creating stress for the driver that leads to
      high risk driving situations and disrupting safe driving through nausea and in
      car vomiting.

PMID- 19578460
TI  - Biological effects and safety in magnetic resonance imaging: a review.
AB  - Since the introduction of Magnetic Resonance Imaging (MRI) as a diagnostic
      technique, the number of people exposed to electromagnetic fields (EMF) has
      increased dramatically. In this review, based on the results of a pioneer study
      showing in vitro and in vivo genotoxic effects of MRI scans, we report an updated
      survey about the effects of non-ionizing EMF employed in MRI, relevant for
      patients' and workers' safety. While the whole data does not confirm a risk
      hypothesis, it suggests a need for further studies and prudent use in order to
      avoid unnecessary examinations, according to the precautionary principle.

PMID- 19578461
TI  - Peer pressure, psychological distress and the urge to smoke.
AB  - BACKGROUND: Psychology and addiction research have found that cigarette smokers
      react with subjective and automatic responses to stimuli associated with smoking.
      This study examines the association between the number of cigarettes smokers
      consume per month and their response to cues derived from peer and psychological
      distress. METHODS: We studied 1,220 adult past and current smokers drawn from a
      national face-to-face interview survey administered in 2004. We defined two types
      of cues possibly triggering a smoker to have a cigarette: peer cues and
      psychological cues. We used ordinary least square linear regressions to analyze
      smoking amount and response to peer and psychological distress cues. RESULTS: We
      found a positive association between amount smoked and cue response: peer cues
      (1.06, 95%CI: 0.74-1.38) and psychological cues (0.44, 95%CI = 0.17-0.70).
      Response to psychological cues was lower among male smokers (-1.62, 95%CI = -2.26
      (-)0.98), but response to psychological cues were higher among those who had
      senior high school level education (0.96, 95%CI = 0.40-1.53) and who began
      smoking as a response to their moods (1.25, 95%CI = 0.68-1.82). CONCLUSIONS:
      These results suggest that both peer cues and psychological cues increase the
      possibility of contingent smoking, and should, therefore, be addressed by anti
      smoking policies and anti-smoking programs. More specifically, special attention
      can be paid to help smokers avoid or counter social pressure to smoke and to help
      smokers resist the use of cigarettes to relieve distress.

PMID- 19578462
TI  - Pattern of smoking habit among Greek blue and white collar workers.
AB  - The aim of our study was to investigate the prevalence of smoking in a Greek
      working population. A questionnaire regarding smoking habit was collected from
      1,005 out of 1,200 blue and white-collar employees (response rate: 84%). The
      overall smoking prevalence was 48.4% and did not differ by sex, age, education,
      and occupation. The mean cigarette consumption per day was 25.54, with no
      difference observed by occupation. The above-mentioned findings, if confirmed by
      further research, are alarming and inconsistent with the prevalent pattern of
      smoking habits in the West.

PMID- 19578463
TI  - The role of health kiosks in 2009: literature and informant review.
AB  - Kiosks can provide patients with access to health systems in public locations,
      but with increasing home Internet access their usefulness is questioned. A
      literature and informant review identified kiosks used for taking medical
      histories, health promotion, self assessment, consumer feedback, patient
      registration, patient access to records, and remote consultations. Sited
      correctly with good interfaces, kiosks can be used by all demographics but many
      'projects' have failed to become routine practice. A role remains for: (a)
      integrated kiosks as part of patient 'flow', (b) opportunistic kiosks to catch
      people's attention. Both require clear 'ownership' to succeed.

PMID- 19578465
TI  - A service-oriented healthcare message alerting architecture in an Asia medical
      center: a case study.
AB  - This paper illustrates how our development team has used some information
      technologies to let physicians obtain an instant abnormal laboratory result
      report for critical patient care services. We have implemented a healthcare
      message alerting system (HMAS) on a healthcare short message service (HSMS)
      engine and the distributed healthcare-oriented service environment (DiHOSE) in
      the National Taiwan University Hospital (NTUH). The HSMS engine has a general
      interface for all applications which could easily send any kind of alerting
      messages. Fundamentally, the DiHOSE uses HL7 standard formats to process the
      information exchange behaviors and can be flexibly extended for reasonable user
      requirements. The disease surveillance subsystem is an integral part of NTUH new
      hospital information system which is based on DiHOSE and the disease surveillance
      subsystem would send alerting messages through the HSMS engine. The latest cell
      phone message alerting subsystem, a case study, in NTUH proved that the DiHOSE
      could integrate the user required functions without much work. We concluded that
      both HSMS and DiHOSE can generalize and extend application demands efficiently.

PMID- 19578464
TI  - Tobacco control: visualisation of research activity using density-equalizing
      mapping and scientometric benchmarking procedures.
AB  - BACKGROUND: Tobacco smoking continues to be a major preventable cause of death
      and disease and therefore tobacco control research is extremely important.
      However, research in this area is often hampered by a lack in funding and there
      is a need for scientometric techniques to display research efforts. METHODS: The
      present study combines classical bibliometric tools with novel scientometric and
      visualizing techniques in order to analyse and categorise research in the field
      of tobacco control. RESULTS: All studies related to tobacco control and listed in
      the ISI database since 1900 were identified by the use of defined search terms.
      Using bibliometric approaches, a continuous increase in qualitative markers such
      as collaboration numbers or citations were found for tobacco control research.
      The combination with density equalizing mapping revealed a distinct global
      pattern of research productivity and citation activity. Radar chart techniques
      were used to visualize bi- and multilateral research cooperation and
      institutional cooperation. CONCLUSIONS: The present study supplies a first
      scientometric approach that visualises research activity in the field of tobacco
      control. It provides data that can be used for funding policy and the
      identification of research clusters.

PMID- 19578466
TI  - Health risk and biological effects of cardiac ionising imaging: from epidemiology
      to genes.
AB  - Cardiac diagnostic or therapeutic testing is an essential tool for diagnosis and
      treatment of cardiovascular disease, but it also involves considerable exposure
      to ionizing radiation. Every exposure produces a corresponding increase in cancer
      risk, and risks are highest for radiation exposure during infancy and
      adolescence. Recent studies on chromosomal biomarkers corroborate the current
      radioprotection assumption showing that even modest radiation load due to cardiac
      catheter-based fluoroscopic procedures can damage the DNA of the cell. In this
      article, we review the biological and clinical risks of cardiac imaging employing
      ionizing radiation. We also discuss the perspectives offered by the use of
      molecular biomarkers in order to better assess the long-term development of
      health effects.

PMID- 19578467
TI  - Fish, mercury, selenium and cardiovascular risk: current evidence and unanswered
      questions.
AB  - Controversy has arisen among the public and in the media regarding the health
      effects of fish intake in adults. Substantial evidence indicates that fish
      consumption reduces coronary heart disease mortality, the leading cause of death
      in developed and most developing nations. Conversely, concerns have grown
      regarding potential effects of exposure to mercury found in some fish. Seafood
      species are also rich in selenium, an essential trace element that may protect
      against both cardiovascular disease and toxic effects of mercury. Such protective
      effects would have direct implications for recommendations regarding optimal
      selenium intake and for assessing the potential impact of mercury exposure from
      fish intake in different populations. Because fish consumption appears to have
      important health benefits in adults, elucidating the relationships between fish
      intake, mercury and selenium exposure, and health risk is of considerable
      scientific and public health relevance. The evidence for health effects of fish
      consumption in adults is reviewed, focusing on the strength and consistency of
      evidence and relative magnitudes of effects of omega-3 fatty acids, mercury, and
      selenium. Given the preponderance of evidence, the focus is on cardiovascular
      effects, but other potential health effects, as well as potential effects of
      polychlorinated biphenyls and dioxins in fish, are also briefly reviewed. The
      relevant current unanswered questions and directions of further research are
      summarized.

PMID- 19578468
TI  - Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a
      review.
AB  - Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar
      to the inhibitory neurotransmitter gamma-aminobutyric acid. Clinical trials have
      demonstrated that 50-100 mg/kg of GHB fractioned into three or six daily doses is
      able to suppress alcohol withdrawal symptoms and facilitates the maintenance of
      abstinence from alcohol. These studies have also shown that GHB craving episodes
      are a very limited phenomenon (about 10-15%). Thus, physicians with access should
      consider the clinical efficacy of GHB as a valid pharmacological tool for the
      treatment of alcohol addiction.

PMID- 19578470
TI  - Let's Talk About Race, Baby! When Whites' and Blacks' Interracial Contact
      Experiences Diverge.
AB  - The present study investigated whether the conditions that make interracial
      contact anxiety-provoking for Whites differ from those that make it anxiety
      provoking for Blacks. Specifically, the present work examined interracial anxiety
      as a function of discussant race (i.e., White or Black) and discussion topic
      (i.e., race-related or race-neutral). To that end, we examined the non-verbal
      behavior of White and Black participants during brief interpersonal interactions.
      Consistent with previous research, White participants behaved more anxiously
      during interracial than same-race interactions. Additionally, White participants
      of interracial interaction behaved more anxiously than their Black interaction
      partners. Furthermore, whereas White participants of interracial interactions
      found race-related discussions no more stressful than race-neutral discussions,
      Black participants of interracial interactions found race-related discussions
      less stressful than race-neutral discussions. The implications of these racial
      and contextual differences in interracial anxiety for improving interracial
      contact and race relations, more broadly, are discussed.

PMID- 19578469
TI  - The Development of Novel Therapies for Rheumatoid Arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory
      disease that affects approximately 0.5 to 1 percent of the adults worldwide and
      commonly results in joint destruction and significant impairment in the quality
      of life. RA is considered as an autoimmune disease with unknown etiology. Many
      pathogenic pathways of RA have been revealed recently, which led to development
      of various novel therapies. OBJECTIVE: The current treatments of RA include 4
      categories: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, non
      biologic disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. In
      this review, we will discuss some of the most recent development in antirheumatic
      therapies. METHODS: Using SciFinder Scholar and PubMed as main searching tools,
      we evaluated various newly developed therapies for RA. Under each drug category,
      emphases are placed on the mode of action, limitation of the drugs and new drug
      candidates from the patents search. Those well-established therapies will only be
      reviewed briefly. CONCLUSION: During the past 20 years, most of the development
      of new therapies is in DMARDs, especially biological DMARDs. With the discovery
      of new pathways and the application of drug delivery strategies, more growth is
      anticipated in this research field.

PMID- 19578471
TI  - Effect of Processing Parameters on Pore Structure and Thickness of Anodic
      Aluminum Oxide (AAO) Tubular Membranes.
AB  - Nanoporous anodic aluminum oxide (AAO) tubular membranes were fabricated from
      aluminum alloy tubes in sulfuric and oxalic acid electrolytes using a two-step
      anodization process. The membranes were investigated for characteristics such as
      pore size, interpore distance and thickness by varying applied voltage and
      electrolyte concentration. Morphology of the membranes was examined using light
      optical and scanning electron microscopy and characterized using ImageJ software.
      Results showed that membranes having narrow pore size and uniform pore
      distribution with parallel channel arrays were obtained. The pore sizes were
      ranging from 14 to 24 nm and the wall thicknesses as high as 76 microm. It was
      found that the pore size increased in direct proportion with the applied voltage
      and inversely with the electrolyte concentration while the interpore distance
      increased linearly with the applied voltage. It was also observed that increase
      in acid concentration increased tubular membrane wall thickness that improved
      mechanical handling. By using anodic alumina technology, robust ceramic tubes
      with uniformly distributed pore-structure and parallel nano-channels of lengths
      and sizes practical for industrial applications were reliably produced in
      quantity.

PMID- 19578472
TI  - Synthesis of Complexable Fluorescent Superparamagnetic Iron Oxide Nanoparticles
      (FL SPIONs) and Cell Labeling for Clinical Application.

PMID- 19578473
TI  - Expanding the Concepts in Protein Structure-Function Relationships and Enzyme
      Kinetics: Teaching using Morpheeins.
AB  - A morpheein is a homo-oligomeric protein that can exist as an ensemble of
      physiologically significant and functionally different alternate quaternary
      assemblies. Morpheeins exist in nature and utilize conformational equilibria
      between different tertiary structures to form distinct oligomers as a means of
      regulating their function. Notably, alternate morpheeins are not misfolded forms
      of a protein; they are differently assembled native states that contain alternate
      subunit conformations. Transitions between alternate morpheein assemblies involve
      oligomer dissociation, conformational change in the dissociated state, and
      reassembly to a different oligomer. These transitions occur in response to the
      protein's environment, e.g., effector molecules, and represent a new model of
      allosteric regulation. The unique features of morpheeins are being revealed
      through detailed characterization of the prototype enzyme, porphobilinogen
      synthase, which exists in a dynamic equilibrium of a high activity octamer, a low
      activity hexamer, and two dimer conformations. Morpheeins are likely far more
      common than previously appreciated. There are, however, both intellectual and
      experimental barriers to recognizing proteins as morpheeins. These barriers
      derive from the way we were taught and continue to teach about protein folding,
      protein purification, protein structure-function relationships, and enzyme
      kinetics. This article explores some of these limitations and encourages
      incorporation of morpheeins into both introductory and advanced biochemistry
      classes.

PMID- 19578474
TI  - Effects of the reinforcement morphology on the fatigue properties of
      hydroxyapatite reinforced polymers.
AB  - The objective of this study was to examine the effects of the hydroxyapatite (HA)
      reinforcement morphology and content on the fatigue behavior of HA reinforced
      high density polyethylene (HDPE). To this end, HDPE was reinforced with 20 and 40
      vol% of either HA whiskers or an equiaxed HA powder, and tested in four-point
      bending fatigue under simulated physiological conditions. The fatigue life,
      mechanical property degradation and failure surfaces were compared between
      experimental groups. HDPE reinforced with HA whiskers exhibited a four- to five
      fold increase (p < 0.001, T-test) in fatigue life compared to an equiaxed powder
      for either the 20 and 40 vol% reinforcement level. Composites containing 40 vol%
      HA exhibited decreased fatigue life compared to those with 20 vol% HA for either
      reinforcement morphology (p < 0.0001, ANOVA). HA whisker reinforced HDPE
      exhibited less stiffness loss, permanent deformation (creep) and energy
      dissipation at a given number of cycles compared to HA powder. Thus, HA whisker
      reinforced HDPE was more tolerant of fatigue damage due to either microcracking
      or polymer plasticity. Scanning electron microscopy of failure surfaces and
      surface microcracks showed evidence of toughening by uncracked ligaments, crack
      tip plasticity, polymer fibril bridging and HA whisker pullout. The results of
      this study suggest that the use of HA whiskers, in place of HA powder, is a
      straightforward means to improve the fatigue life and damage tolerance of HA
      reinforced polymers for synthetic bone substitutes.

PMID- 19578475
TI  - Neighborhood History as a Factor Shaping Syringe Distribution Networks Among Drug
      Users at a U.S. Syringe Exchange.
AB  - Throughout the US, high-visibility drug markets are concentrated in neighborhoods
      with few economic opportunities, while drug buyers/users are widely dispersed. A
      study of Pittsburgh Syringe Exchange participants provides data on travel between
      and network linkages across neighborhoods with different levels of drug activity.
      There are distinct racial patterns to syringe distribution activity within
      networks and across neighborhoods. Pittsburgh's history suggests these patterns
      emerge from historical patterns of social and economic development. Study data
      demonstrate the ability of IDUs to form long term social ties across racial and
      geographic boundaries and use them to reduce the risk of HIV transmission.

PMID- 19578476
TI  - Multifunctional Particles: Magnetic Nanocrystals and Gold Nanorods Coated with
      Fluorescent Dye-Doped Silica Shells.
AB  - Multifunctional colloidal core-shell nanoparticles of magnetic nanocrystals (of
      iron oxide or FePt) or gold nanorods encapsulated in silica shells doped with the
      fluorescent dye, Tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate (Rubpy)
      were synthesized. The as-prepared magnetic nanocrystals are initially hydrophobic
      and were coated with silica using a microemulsion approach, while the as-prepared
      gold nanorods are hydrophilic and were coated with silica using a Stober-type of
      process. Each approach yielded monodisperse nanoparticles with uniform
      fluorescent dye-doped silica shells. These colloidal heterostructures have the
      potential to be used as dual-purpose tags-exhibiting a fluorescent signal that
      could be combined with either dark-field optical contrast (in the case of the
      gold nanorods), or enhanced contrast in magnetic resonance images (in the case of
      magnetic nanocrystal cores). The optical and magnetic properties of the
      fluorescent silica-coated gold nanorods and magnetic nanocrystals are reported.

PMID- 19578478
TI  - New Strategy for the Search of Natural Biologically Active Substances.
AB  - The modern pharmaceutics actively screens an immense diversity of substances
      occurring in plants and other natural resources in the search for new effective
      medicinal agents. The Global Institute for Bioexploration (GIBEX) established by
      joint efforts of Rutgers University and the University of Illinois (United
      States) represents the organizational core of international scientific community
      whose activity is directed towards the search and development of new medicinal
      preparations from natural raw materials. The basis of GIBEX activity is the
      transfer of modern screening technologies to countries and geographical regions
      characterized by remarkable biodiversity. The GIBEX goals are to encourage the
      search for new natural biologically active substances, to maintain biodiversity,
      and to monitor the natural resources conservation.

PMID- 19578477
TI  - Concepts in the pathogenesis of rabies.
AB  - Rabies is a zoonotic disease that remains an important public health problem
      worldwide and causes more than 70,000 human deaths each year. The causative agent
      of rabies is rabies virus (RV), a negative-stranded RNA virus of the rhabdovirus
      family. Neuroinvasiveness and neurotropism are the main features that define the
      pathogenesis of rabies. Although RV pathogenicity is a multigenic trait involving
      several elements of the RV genome, the RV glycoprotein plays a major role in RV
      pathogenesis by controlling the rate of virus uptake and trans-synaptic virus
      spread, and by regulating the rate of virus replication. Pathogenic street RV
      strains differ significantly from tissue culture-adapted RV strains in their
      neuroinvasiveness. Whereas street RV strains are highly neuroinvasive, most
      tissue culture-adapted RV strains have either no or only limited ability to
      invade the CNS from a peripheral site. The high neuroinvasiveness of pathogenic
      street RVs is, at least in part, due to their ability to evade immune responses
      and to conserve the structures of neurons. The finding that tissue culture
      adapted RV strains replicate very fast and induce strong innate and adaptive
      immune responses opens new avenues for therapeutic intervention against rabies.

PMID- 19578479
TI  - The Relation of Rigidity Across Relationships With Symptoms and Functioning: An
      Investigation With the Revised Central Relationship Questionnaire.
AB  - The belief that rigidity across relationships is related to greater symptoms and
      poorer functioning commonly informs the practice of many psychodynamic and
      interpersonal therapists. Using a profile correlation approach, we tested this
      hypothesis in a sample of 250 clients and 90 undergraduate control participants.
      Symptoms and functioning were assessed with the Inventory of Interpersonal
      Problems (IIP), Global Assessment of Functioning scale, and Brief Symptom
      Inventory. A revised version of the empirically-derived Central Relationship
      Questionnaire (CRQ) was used to measure interpersonal patterns. Revisions were
      made to the CRQ to increase the interpersonal dimensions it captured, reduce its
      length, and model a higher-order factor structure. The psychometric properties of
      the revised CRQ were found to be adequate. Rigidity as measured with the CRQ was
      not related to rigidity measured with the IIP (amplitude) and did not differ
      significantly among individuals with different interpersonal problems or DSM-IV
      diagnoses. Contrary to theory, however, greater rigidity across relationships was
      related to fewer symptoms and interpersonal problems. These relations did not
      appear due to the valence or the extremeness of the interpersonal patterns used
      in the estimation of rigidity.

PMID- 19578480
TI  - MICROPATTERNING OF GOLD SUBSTRATES BASED ON POLY(PROPYLENE SULFIDE-BL-ETHYLENE
      GLYCOL), (PPS-PEG) BACKGROUND PASSIVATION AND THE MOLECULAR-ASSEMBLY PATTERNING
      BY LIFT-OFF (MAPL) TECHNIQUE.
AB  - Poly(propylene sulfide-bl-ethylene glycol (PPS-PEG) is an amphiphilic block
      copolymer that spontaneously adsorbs onto gold from solution. This results in the
      formation of a stable polymeric layer that renders the surface protein resistant
      when an appropriate architecture is chosen. The established molecular assembly
      patterning by lift-off (MAPL) technique can convert a prestructured resist film
      into a pattern of biointeractive chemistry and a noninteractive background.
      Employing the MAPL technique, we produced a micron-scale PPS-PEG pattern on a
      gold substrate, and then characterized the patterned structure with Time-of
      Flight Secondary Ion Mass Spectrometry (TOF-SIMS) and Atomic Force Microscopy
      (AFM). Subsequent exposure of the PPS-PEG/gold pattern to protein adsorption
      (full human serum) was monitored in situ; SPR-imaging (i-SPR) shows a selective
      adsorption of proteins on gold, but not on PPS-PEG areas. Analysis shows a
      reduction of serum adsorption up to 93% on the PPS-PEG areas as compared to gold,
      in good agreement with previous analysis of homogenously adsorbed PPS-PEG on
      gold. MAPL patterning of PPS-PEG block copolymers is straightforward, versatile
      and reproducible, and may be incorporated into biosensor-based surface analysis
      methods.

PMID- 19578481
TI  - Cost-effective screening for breast cancer worldwide: current state and future
      directions.
AB  - Affordability of healthcare is highly limited by its skyrocketing cost. Access to
      screening and diagnostic medical equipment and medicine in developing countries
      is inadequate for the majority of the population. There is a tremendous worldwide
      need to detect breast cancer at its earliest stage. These needs must be balanced
      by the ability of countries to provide breast cancer screening technology to
      their populations. We reviewed the diagnostic accuracy, procedure cost and cost
      effectiveness of currently available technique for breast screening and diagnosis
      including clinical breast examination, mammography, ultrasound, magnetic
      resonance imaging, biopsy and a new modality for cancer diagnostics termed
      elasticity imaging that has emerged in the last decade. Clinical results
      demonstrate that elasticity imaging even in its simplest and least sophisticated
      versions, like tactile imaging, has significant diagnostic potential comparable
      and exceeding that of conventional imaging techniques. In view of many countries
      with limited resources, effective yet less expensive modes of screening must be
      considered worldwide. The tactile imaging is one method that has the potential to
      provide cost-effective breast cancer screening and diagnostics.

PMID- 19578483
TI  - EMPLOYING TOPOGRAPHICAL HEIGHT MAP IN COLONIC POLYP MEASUREMENT AND FALSE
      POSITIVE REDUCTION.
AB  - CT Colonography (CTC) is an emerging minimally invasive technique for screening
      and diagnosing colon cancers. Computer Aided Detection (CAD) techniques can
      increase sensitivity and reduce false positives. Inspired by the way radiologists
      detect polyps via 3D virtual fly-through in CTC, we borrowed the idea from
      geographic information systems to employ topographical height map in colonic
      polyp measurement and false positive reduction. After a curvature based filtering
      and a 3D CT feature classifier, a height map is computed for each detection using
      a ray-casting algorithm. We design a concentric index to characterize the
      concentric pattern in polyp height map based on the fact that polyps are
      protrusions from the colon wall and round in shape. The height map is optimized
      through a multi-scale spiral spherical search to maximize the concentric index.
      We derive several topographic features from the map and compute texture features
      based on wavelet decomposition. We then send the features to a committee of
      support vector machines for classification. We have trained our method on 394
      patients (71 polyps) and tested it on 792 patients (226 polyps). Results showed
      that we can achieve 95% sensitivity at 2.4 false positives per patient and the
      height map features can reduce false positives by more than 50%. We compute the
      polyp height and width measurements and correlate them with manual measurements.
      The Pearson correlations are 0.74 (p=0.11) and 0.75 (p=0.17) for height and
      width, respectively.

PMID- 19578485
TI  - The Kinematic Basis of ACL Reconstruction.
AB  - The goals of anterior cruciate ligament (ACL) reconstruction are to restore knee
      stability and function and to preserve joint health. Static tests for antero
      posterior laxity (e.g. Lachman test or KT-1000 arthrometer) have typically shown
      restoration of normal or near-normal laxity with a variety of modern ACL
      reconstruction techniques. However, ACL reconstruction has failed to prevent
      early onset of osteoarthritis, and there is growing evidence that traditional
      single-bundle ACL reconstruction does not restore normal knee mechanics under
      functional loading conditions. ACL reconstruction may fail to restore normal
      rotational stability during the pivot shift. Abnormal internal-external rotation
      and ab/adduction have been reported after ACL reconstruction during normal daily
      activities like walking and running. Recently, cadaveric studies have shown the
      potential superiority of ACL double bundle (DB) reconstruction for restoring
      anatomy and mechanical function. However, clinical data demonstrating the clear
      superiority of DB reconstruction is lacking, due to the absence of well
      controlled clinical studies. Additionally, dynamic knee function after anatomic
      DB ACL has yet to be assessed comprehensively.

PMID- 19578482
TI  - VASCULAR INFLAMMATION AND ATHEROGENESIS ARE ACTIVATED VIA RECEPTORS FOR PAMPs AND
      SUPPRESSED BY REGULATORY T CELLS.
AB  - Despite significant advances in identifying the risk factors and elucidating
      atherosclerotic pathology, atherosclerosis remains the leading cause of morbidity
      and mortality in industrialized society. These risk factors independently or
      synergistically lead to chronic vascular inflammation, which is an essential
      requirement for the progression of atherosclerosis in patients. However, the
      mechanisms underlying the pathogenic link between the risk factors and
      atherosclerotic inflammation remain poorly defined. Significant progress has been
      made in two major areas, which are determination of the roles of the receptors
      for pathogen-associated molecular patterns (PAMPs) in initiation of vascular
      inflammation and atherosclerosis, and characterization of the roles of regulatory
      T cells in suppression of vascular inflammation and atherosclerosis. In this
      review, we focus on three related issues: (1) examining the recent progress in
      endothelial cell pathology, inflammation and their roles in atherosclerosis; (2)
      analyzing the roles of the receptors for pathogen-associated molecular patterns
      (PAMPs) in initiation of vascular inflammation and atherosclerosis; and (3)
      analyzing the advances in our understanding of suppression of vascular
      inflammation and atherosclerosis by regulatory T cells. Continuous improvement of
      our understanding of the risk factors involved in initiation and promotion of
      artherogenesis, will lead to the development of novel therapeutics for ischemic
      stroke and cardiovascular diseases.

PMID- 19578487
TI  - Evidence-based management strategies for treatment of chronic wounds.
AB  - The care and management of patients with chronic wounds and their far-reaching
      effects challenge both the patient and the practitioner. Further complicating
      this situation is the paucity of evidence-based treatment strategies for chronic
      wound care. After searching both MEDLINE and Cochrane databases, we reviewed
      currently available articles concerning chronic wound care. Utilizing this
      information, we have outlined a review of current, evidence-based concepts as
      they pertain to the treatment of chronic wounds, focusing on fundamental
      treatment principles for the management of venous, arterial, diabetic, and
      pressure ulcers. Individualized treatment options as well as general wound
      management principles applicable to all varieties of chronic wounds are
      described. Classification and treatment guidelines as well as the adoption of the
      TIME acronym facilitate an organized conceptional approach to wound care. In so
      doing, individual aspects of generalized wound care such as debridement,
      infection, and moisture control as well as attention to the qualities of the
      wound edge are comprehensively evaluated, communicated, and addressed. Effective
      adjuvant agents for the therapy of chronic wounds including nutritional and
      social support measures are listed, as is a brief review of strategies helpful
      for preventing recurrence. An appreciation of evidence-based treatment pathways
      and an understanding of the pathophysiology of chronic wounds are important
      elements in the management of patients with chronic wounds. To achieve effective
      and long-lasting results, a multidisciplinary approach to patient care, focused
      on the education and coordination of patient, family as well as medical and
      support staff can prove invaluable.

PMID- 19578486
TI  - Modifying skin pigmentation - approaches through intrinsic biochemistry and
      exogenous agents.
AB  - Rates of skin cancer continue to increase despite the improved use of traditional
      sunscreens to minimize damage from ultraviolet radiation. The public perception
      of tanned skin as being healthy and desirable, combined with the rising demand
      for treatments to repair irregular skin pigmentation and the desire to increase
      or decrease constitutive skin pigmentation, arouses great interest
      pharmaceutically as well as cosmeceutically. This review discusses the intrinsic
      biochemistry of pigmentation, details mechanisms that lead to increased or
      decreased skin pigmentation, and summarizes established and potential hyper- and
      hypo-pigmenting agents and their modes of action.

PMID- 19578489
TI  - Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths
      worldwide. Effective treatment of HCC patients is hampered by the lack of
      sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP), the
      currently used HCC marker, misses 30%-50% of HCC patients, who therefore remain
      undiagnosed and untreated. In order to identify novel diagnostic markers that can
      be used individually or in combination with AFP, we used an antibody array
      platform to detect the levels of candidate proteins in the plasma of HCC patients
      (n = 48) and patients with chronic hepatitis B or C viral infections (n = 19)
      (both of which are the major risk factors of HCC). We identified 7 proteins that
      significantly differentiate HCC patients from hepatitis patients (p < 0.05) (AFP,
      CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1). Importantly, we also identified 8
      proteins that significantly differentiate HCC patients with 'normal' levels of
      AFP (< 20 ng/ml) from hepatitis patients (p < 0.05) (IL1RN, IFNG, CDKN1A, RETN,
      CXCL14, CTNNB, FGF2, and SELL). These markers are potentially important
      complementary markers to AFP. Using an independent immunoassay method in an
      independent group of 23 HCC patients and 22 hepatitis patients, we validated that
      plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020). In
      conclusion, we used an antibody array platform to identify potential circulating
      diagnostic markers of HCC, some of which may be valuable when used in combination
      with AFP. The clinical utility of these newly identified HCC diagnostic markers
      needs to be systematically evaluated.

PMID- 19578488
TI  - An Evaluation of the Clinical Evidence on the Role of Inflammation and Oxidative
      Stress in Smoking-Mediated Cardiovascular Disease.
AB  - The number of fatalities due to cardiovascular disease (CVD) continues to be far
      ahead of loss of human life caused by any other type of disease worldwide.
      According to the WHO, the annual global tobacco death toll is already 8.4 million
      and will reach 10 million by the year 2025. However, in contrast to other
      modifiable primary risk factors for CVD such as obesity, primary prevention
      strategies for smokers unable to quit are not available to date. This Review, by
      adopting the principles of evidence-based medicine, summarizes the most recent
      clinical studies on CVD in smokers, and concludes by suggesting a novel primary
      prevention strategy for CVD in smokers unable to quit. Evidence gathered from
      mechanistic studies involving basic research as well as large population-based
      approaches point to oxidative stress as the major insult imposed by cigarette
      smoke (CS), and a state of systemic inflammation, as signified by increased hs
      (high sensitivity) CRP levels in smokers, as the decisive pro-atherogenic
      response of the body to the initial insult. Since we identified oxidative stress
      induced by heavy metals as a significant pro-atherogenic activity of CS,
      strategies aimed at detoxifying heavy metals and combating inflammation appear as
      plausible approaches to counteract the accelerated onset of CVD in smokers. For
      this purpose, we discuss metal chelating agents and statins as promising novel
      primary prevention strategies in smokers unable to quit.

PMID- 19578490
TI  - Marker of Bone Resorption in Acute Response to Exogenous or Endogenous
      Parathyroid Hormone.
AB  - Parathyroid hormone (PTH) changes morphology of osteoclasts within minutes after
      its systemic administration. The aim of our study was to test in healthy men
      whether both exogenous and endogenous PTH could change acutely (minutes to hours)
      the serum cross-linked C-telopeptide of type I collagen (beta CTX), which is
      released during osteoclastic resorption of bone. Twelve healthy men (age range 24
      34 yr) were each studied during 180 min on a control period, after a single
      subcutaneous injection of teriparatide, and after 30 min EDTA infusion to
      stimulate endogenous PTH secretion. The tests were started after overnight fast,
      3 h after a standard calcium load. The EDTA infusion induced a significant
      decrease in serum ionized calcium (by 8.5% at 33 min) and a significant increase
      in plasma PTH (by 305% at 33 min). Both the EDTA and teriparatide resulted in a
      significant increase in beta CTX (p < 0.001) with maximum increases of 64% and
      80%, respectively. A mild, but significant decrease in beta CTX was observed
      during the control test period. In conclusion, single-dose teriparatide injection
      as well as a stimulation of endogenous PTH in healthy men results in an acute
      increase of the bone resorption marker.

PMID- 19578491
TI  - Sample Stability and Protein Composition of Saliva: Implications for Its Use as a
      Diagnostic Fluid.
AB  - Saliva is an easy accessible plasma ultra-filtrate. Therefore, saliva can be an
      attractive alternative to blood for measurement of diagnostic protein markers.
      Our aim was to determine stability and protein composition of saliva. Protein
      stability at room temperature was examined by incubating fresh whole saliva with
      and without inhibitors of proteases and bacterial metabolism followed by Surface
      Enhanced Laser Desorption/Ionization (SELDI) analyses. Protein composition was
      determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) fractionation of saliva proteins followed by digestion of excised bands and
      identification by liquid chromatography tandem mass spectrometry (LC-MS/MS).
      Results show that rapid protein degradation occurs within 30 minutes after sample
      collection. Degradation starts already during collection. Protease inhibitors
      partly prevented degradation while inhibition of bacterial metabolism did not
      affect degradation. Three stable degradation products of 2937 Da, 3370 Da and
      4132 Da were discovered which can be used as markers to monitor sample quality.
      Saliva proteome analyses revealed 218 proteins of which 84 can also be found in
      blood plasma. Based on a comparison with seven other proteomics studies on whole
      saliva we identified 83 new saliva proteins. We conclude that saliva is a
      promising diagnostic fluid when precautions are taken towards protein breakdown.

PMID- 19578492
TI  - Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth
      Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages.
AB  - YKL-39 is a Glyco_18 domain containing chitinase-like protein which is currently
      recognized as a biomarker for the activation of chondrocytes and the progress of
      the osteoarthritis in human. YKL-39 was identified as an abundantly secreted
      protein in primary culture of human articular chondrocytes. Two biological
      activities of YKL-39 might contribute to the disease progression. One is the
      induction of autoimmune response and second is the participation in tissue
      remodeling. Other mammalian chitinase-like proteins including chitotriosidase, SI
      CLP, YKL-40 and YM1 are expressed by macrophages in various pathological
      conditions. In contrast, YKL-39 was never reported to be produced by macrophages.
      We used in vitro model of human monocyte-derived macrophage differentiation to
      analyse regulation of YKL-39 expression. Expression of YKL-39 was examined by
      real-time RT-PCR. CD14+ MACS sorted human monocytes differentiated for 6 days
      under different stimulations including IFNgamma, IL-4, dexamethasone and TGF
      beta. We found that both IL-4 and TGF-beta have weak stimulatory effect on YKL-39
      expression in all donors tested (3.2 +/- 1.7 fold, p = 0.006 and 6.3 +/- 3.1
      fold, p = 0.014 respectively). However the combination of IL-4 and TGF-beta had
      strong stimulatory effect on the expression of YKL-39 in all analysed individual
      macrophage cultures (34 +/- 36 fold, p = 0.05). IFN-gamma did not show
      statistically significant effect of YKL-39 mRNA expression. Presence of
      dexamethasone almost completely abolished the stimulatory effects of IL-4 and TGF
      beta. In summary, we show here for the first time, that human cells of monocyte
      origin are able to produce YKL-39. Maturation of monocyte derived macrophages in
      the presence of Th2 cytokine IL-4 and TGF-beta leads to the strong activation of
      YKL-39 expression. Thus elevated levels of YKL-39 observed during chronic
      inflammations can not be attributed solely to the activity of chondrocytes. In
      perspective, YKL-39 might serve as a useful biomarker to detect macrophage
      specific response in pathologies like tumour, atherosclerosis and Alzheimer
      disease.

PMID- 19578493
TI  - Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure
      in Early-Stage Cervical Cancer.
AB  - Tumor hypoxia is associated with adverse outcome in many malignancies. The goal
      of this study was to determine if elevated expression of carbonic anhydrase IX
      (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical
      cancer. The charts of all patients with early-stage cervical cancer, primarily
      FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were
      reviewed. Adequate pathologic specimens from patients who recurred or who had at
      least three years follow-up and remained disease-free were stained for CAIX. An
      immunohistochemical score (IHC) was generated from the extent/intensity of
      staining. Outcome, as measured by freedom from recurrence (FFR), distant
      metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age,
      IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76
      non-relapsing patients were evaluated. In univariate analysis, +LN, though not
      IHC or histology, was a significant predictor of any recurrence. Both +LN and
      higher IHC were associated with decreased FFDM but not FFLR. Patients with both
      +LN and elevated IHC more frequently exhibited distant metastases as first site
      of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither
      feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis,
      only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p =
      0.0015) though there was a strong trend with elevated CAIX expression (p =
      0.069). Elevated CAIX expression is associated with more frequent distant
      metastases in early-stage cervical cancer, suggesting that patients with this
      characteristic may benefit from more aggressive treatment.

PMID- 19578494
TI  - Cellular Adhesion Molecules in Healthy Subjects: Short Term Variations and
      Relations to Flow Mediated Dilation.
AB  - The objective was primarily to describe short term intra-individual variation in
      serum levels of soluble adhesion molecules (sCAMs: E-selectin, P-selectin,
      intercellular adhesion molecule-1(sICAM-1) and vascular cellular adhesion
      molecule-1(sVCAM-1)) in healthy subjects. Secondly, sCAMs were correlated to
      brachial artery flow mediated vasodilation (FMD).Forty healthy subjects aged 24
      66 years had sCAMs measured twice with 4 week intervals and short-term intra
      individual variation was estimated as variation in the paired measurements after
      correcting for the analytical precision of the used method. At baseline, brachial
      FMD was measured.No difference was observed in mean sCAMs in the whole study
      group. Estimated intra-subject variations in sCAMs were 7.6-11.3%. In a
      regression analysis, significant negative association was found between sE
      selectin and FMD after controlling for possible confounders (p < 0.04) while no
      significant correlation could be demonstrated between the other sCAMs and FMD.In
      conclusion, short term intra-individual variations in sCAMs were 7.6-11.3% in
      healthy subjects. We also found a significant negative association between sE
      selectin and FMD, indicating an possible association between inflammation and
      dysfunction of the vascular endothelium; however further studies are required to
      confirm this preliminary finding.

PMID- 19578495
TI  - Candidate List of yoUr Biomarker (CLUB): A Web-based Platform to Aid Cancer
      Biomarker Research.
AB  - CLUB ("Candidate List of yoUr Biomarkers") is a freely available, web-based
      resource designed to support Cancer biomarker research. It is targeted to provide
      a comprehensive list of candidate biomarkers for various cancers that have been
      reported by the research community. CLUB provides tools for comparison of marker
      candidates from different experimental platforms, with the ability to filter,
      search, query and explore, molecular interaction networks associated with cancer
      biomarkers from the published literature and from data uploaded by the community.
      This complex and ambitious project is implemented in phases. As a first step, we
      have compiled from the literature an initial set of differentially expressed
      human candidate cancer biomarkers. Each candidate is annotated with information
      from publicly available databases such as Gene Ontology, Swiss-Prot database,
      National Center for Biotechnology Information's reference sequences, Biomolecular
      Interaction Network Database and IntAct interaction. The user has the option to
      maintain private lists of biomarker candidates or share and export these for use
      by the community. Furthermore, users may customize and combine commonly used sets
      of selection procedures and apply them as a stored workflow using selected
      candidate lists. To enable an assessment by the user before taking a candidate
      biomarker to the experimental validation stage, the platform contains the
      functionality to identify pathways associated with cancer risk, staging,
      prognosis, outcome in cancer and other clinically associated phenotypes. The
      system is available at http://club.bii.a-star.edu.sg.

PMID- 19578496
TI  - Genomic and Proteomic Biomarker Discovery in Neurological Disease.
AB  - Technology for high-throughout scanning of the human genome and its encoded
      proteins have rapidly developed to allow systematic analyses of human disease.
      Application of these technologies is becoming an increasingly effective approach
      for identifying the biological basis of genetically complex neurological
      diseases. This review will highlight significant findings resulting from the use
      of a multitude of genomic and proteomic technologies toward biomarker discovery
      in neurological disorders. Though substantial discoveries have been made, there
      is clearly significant promise and potential remaining to be fully realized
      through increasing use of and further development of -omic technologies.

PMID- 19578497
TI  - Repeatedly Heading a Soccer Ball Does Not Increase Serum Levels of S-100B, a
      Biochemical Marker of Brain Tissue Damage: an Experimental Study.
AB  - OBJECTIVES: The aim of the study was to analyse whether the controlled heading of
      soccer balls elicits increased serum concentrations of a biochemical marker of
      brain tissue damage S-100B. METHODS: Nineteen male soccer players were randomly
      divided into two groups, A and B. Group A headed a soccer ball falling from 18 m
      five times, while group B served as controls (no heading). Blood samples were
      taken before and 0.5 h, 2 h and 4 h after the heading for analysis of S-100B.
      RESULTS: No statistically significant (p > 0.05) increases in serum
      concentrations of S-100B were encountered in group A at 0.5 h (0.109 +/-0.024
      mug/L), 2 h (0.098 +/- 0.026 mug/L), and 4 h (0.113 +/- 0.035 mug/L) when the
      blood samples obtained before and after the heading were compared (0.157 +/-
      0.134 mug/L). No statistically significant difference was found when the serum
      concentrations of S-100B were compared between groups A and B either before or
      after heading. CONCLUSIONS: Heading a soccer ball dropped from a height of 18 m
      five times was not found to cause an increase in serum concentrations of S-100B,
      indicating that the impact was not sufficient to cause biochemically discernible
      damage of brain tissue.

PMID- 19578498
TI  - Novel Biomarkers Associated with Deep Venous Thrombosis: A Comprehensive Review.
AB  - Primary and recurrent venous thromboembolic disease (VTE, deep venous thrombosis
      and pulmonary embolism) remain a significant source of morbidity and mortality in
      the hospitalized patient. Non-specific subjective complaints and lack of specific
      objective findings related to acute deep venous thrombosis (DVT) and pulmonary
      embolism (PE) complicate the diagnosis. There remains no single serum marker
      available to exclusively confirm the diagnosis of VTE. While D-dimer is highly
      sensitive and useful for diagnostic exclusion, it lacks the specificity necessary
      for diagnostic confirmation resulting in the need for a variety of additional
      studies (i.e.: duplex ultrasound, venography, V/Q scanning, helical thoracic and
      pelvic CT scans and pulmoary angiography). There is evolving research supporting
      the utility of various plasma markers as novel "biomarkers" for VTE including
      selectins, microparticles, interleukin-10 and other cytokines. This review
      attempts to examine recent literature assessing the utility of P-selectin,
      microparticles, D-dimer, E-selectin, thrombin, interleukins and fibrin monomers
      in the diagnosis and guidance of therapy for VTE.

PMID- 19578501
TI  - Serum and Ascitic Fluid Superoxide Dismutase and Malondialdehyde Levels in
      Patients with Cirrhosis.
AB  - SUMMARY: Serum and ascitic fluid superoxide dismutase (SOD) and malondialdehyde
      (MDA) levels were measured in 43 patients with cirrhosis and in a 10 healthy
      control group. Compensated cirrhotic patients had no clinically detectable
      ascites, but decompensated patients had massive ascites. Cirrhotic patients were
      divided into three groups: patients with compensated cirrhosis (n = 16), patients
      with decompensated cirrhosis with Spontaneous bacterial peritonitis (SBP) (n =
      14), and patients with decompensated cirrhosis without SBP (n = 13). All
      cirrhotic patients in the experimental group had significantly higher serum SOD
      (p < 0.001) and MDA levels (p < 0.01) than those in the control group. There were
      no significant differences with respect to serum SOD and MDA levels among the
      three different groups of patients. There was no remarkable difference in ascitic
      fluid SOD and MDA levels between decompensated cirrhotic patients with and
      without SBP (p > 0.05). These results suggest that the increase in serum SOD and
      MDA levels are not related to the presence of SBP and the status of liver
      cirrhosis. To sum up, clarifying the impact of increased serum SOD and MDA levels
      in cirrhotic patients needs further investigation.

PMID- 19578500
TI  - Biomarkers in Acute Kidney Injury.

PMID- 19578499
TI  - Proteomic Biomarkers of Atherosclerosis.
AB  - SUMMARY: Biomarkers provide a powerful approach to understanding the spectrum of
      cardiovascular diseases. They have application in screening, diagnostic,
      prognostication, prediction of recurrences and monitoring of therapy. The "omics"
      tool are becoming very useful in the development of new biomarkers in
      cardiovascular diseases. Among them, proteomics is especially fitted to look for
      new proteins in health and disease and is playing a significant role in the
      development of new diagnostic tools in cardiovascular diagnosis and prognosis.
      This review provides an overview of progress in applying proteomics to
      atherosclerosis. First, we describe novel proteins identified analysing
      atherosclerotic plaques directly. Careful analysis of proteins within the
      atherosclerotic vascular tissue can provide a repertoire of proteins involved in
      vascular remodelling and atherogenesis. Second, we discuss recent data concerning
      proteins secreted by atherosclerotic plaques. The definition of the atheroma
      plaque secretome resides in that proteins secreted by arteries can be very good
      candidates of novel biomarkers. Finally we describe proteins that have been
      differentially expressed (versus controls) by individual cells which constitute
      atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages
      and foam cells) as well as by circulating cells (monocytes, platelets) or novel
      biomarkers present in plasma.

PMID- 19578502
TI  - Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE
      Deficient Mice.
AB  - BACKGROUND: Current drug therapy of atherosclerosis is focused on treatment of
      major risk factors, e.g. hypercholesterolemia while in the future direct disease
      modification might provide additional benefits. However, development of medicines
      targeting vascular wall disease is complicated by the lack of reliable
      biomarkers. In this study, we took a novel approach to identify circulating
      biomarkers indicative of drug efficacy by reducing the complexity of the in vivo
      system to the level where neither disease progression nor drug treatment was
      associated with the changes in plasma cholesterol. RESULTS: ApoE-/- mice were
      treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor
      simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques
      in brachiocephalic arteries, however simvastatin paradoxically stimulated
      atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood
      and vascular samples were obtained from the same animals. In the whole blood RNA
      samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic
      drug effects. In the plasma, several proteins, e.g. IL-1beta, IL-18 and MMP9
      followed similar trends while protein readout was less sensitive than RNA
      analysis. CONCLUSION: In this study, we have identified inflammation-related
      whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of
      ramipril and pro-atherogenic effects of simwastatin in a mouse model of
      atherosclerosis. This opens an opportunity for early, non-invasive detection of
      direct drug effects on atherosclerotic plaques in complex in vivo systems.

PMID- 19578504
TI  - Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene.
AB  - Benzene is used as a general purpose solvent. Benzene metabolism starts from
      phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by
      benzene still remains a toxicologic problem. Tumor related genes and immune
      responsive genes have been studied in patients suffering from benzene exposure.
      However, gene expression profiles and pathways related to its hepatotoxicity are
      not known. This study reports the results obtained in the liver of BALB/C mice
      (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six
      days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji.,
      Japan). Histopathological observations were made to support gene expression data.
      c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After
      six days of benzene exposure, twenty five genes were down regulated whereas
      nineteen genes were up-regulated. These gene expression changes were found to be
      related to pathways of biotransformation, detoxification, apoptosis, oxidative
      stress and cell cycle. It has been shown for the first time that genes
      corresponding to circadian rhythms are affected by benzene. Results suggest that
      gene expression profile might serve as potential biomarkers of hepatotoxicity
      during benzene exposure.

PMID- 19578503
TI  - Chemical Biomarkers of Human Breast Milk Pollution.
AB  - Human milk is, without question, the best source of nutrition for infants
      containing the optimal balance of fats, carbohydrates and proteins for developing
      babies. Breastfeeding provides a range of benefits for growth, immunity and
      development building a powerful bond between mother and her child. Recognition of
      the manifold benefits of breast milk has led to the adoption of breast-feeding
      policies by numerous health and professional organizations such as the World
      Health Organization and American Academy of Pediatrics.In industrially developed
      as well as in developing nations, human milk contamination by toxic chemicals
      such as heavy metals, dioxins and organohalogen compounds, however, is widespread
      and is the consequence of decades of inadequately controlled pollution. Through
      breastfeeding, the mother may transfer to the suckling infant potentially toxic
      chemicals to which the mother has previously been exposed.In the present review,
      environmental exposure, acquisition and current levels of old and emerging
      classes of breast milk pollutants are systematically presented. Although
      scientific evidences indicated that the advantages of breast-feeding outweigh any
      risks from contaminants, it is important to identify contaminant trends, to
      locate disproportionately exposed populations, and to take public health measures
      to improve chemical BM pollution as possible.

PMID- 19578506
TI  - Excision Repair Cross-Complementation Group 1 Enzyme as a Molecular Determinant
      of Responsiveness to Platinum-Based Chemotherapy for non Small-Cell Lung Cancer.
AB  - Although platinum-based chemotherapy remains the "standard" in advanced non small
      cell lung cancer, not all patients derive clinical benefit from such a treatment.
      Hence, the development of predictive biomarkers able to identify lung cancer
      patients who are most likely to benefit from cisplatin-based chemotherapy has
      become a scientific priority. Among the molecular pathways involved in DNA damage
      control after chemotherapy, the nucleotide excision repair (NER) is a critical
      process for the repair of DNA damage caused by cisplatin-induced DNA adducts.
      Many reports have explored the role of the excision repair cross-complementation
      group 1 enzyme (ERCC1) expression in the repair mechanism of cisplatin-induced
      DNA adducts in cancer cells.Using immunohistochemistry in resected tumors from
      patients included in the International Adjuvant Lung Cancer Trial, the study of
      important biomarkers showed that high ERCC1 protein expression was associated
      with improved survival in chemo-naive patients. On the contrary, the benefit of
      adjuvant cisplatin-based chemotherapy was more profound in patients with low
      ERCC1 expression. In a prospective cohort studying mRNA expression in tumor
      biopsies from patients receiving customized therapy with cisplatin and
      gemcitabine depending on the molecular profile of the tumour, results showed that
      patients with low ERCC1 mRNA expression had a longer median survival compared to
      those with high expression. These data suggest the potent use of ERCC1 as a
      molecular predictor of clinical resistance to platinum-based chemotherapy in the
      adjuvant setting of NSCLC. Nevertheless, optimization of methodology, including
      standardization of technical procedures, as well as validation of ERCC1 protein
      expression in large prospective cohorts, seem necessary before any routine
      immunohistochemical validation of ERCC1 can be implemented in daily practice.

PMID- 19578507
TI  - Comparison of the Calibration Standards of Three Commercially Available Multiplex
      Kits for Human Cytokine Measurement to WHO Standards Reveals Striking
      Differences.
AB  - Serum parameters as indicators for the efficacy of therapeutic drugs are
      currently in the focus of intensive research. The induction of certain cytokines
      (or cytokine patterns) is known to be related to the status of the immune
      response e.g. in regulating the T(H)1/T(H)2 balance. Regarding their potential
      value as surrogate parameters in clinical trials and subsequently for the
      assignment of treatment efficacy, the accurate and reliable determination of
      cytokines in patient serum is mandatory. Because serum samples are precious and
      limited, test methods-like the xMAP multiplex technology-that allow for the
      simultaneous determination of a variety of cytokines from only a small sample
      aliquot, can offer great advantages.We here have compared multiplex kits from
      three different manufactures and found striking differences upon standardizing
      using WHO standards for selected cytokines. We therefore extended our xMAP
      multiplex measurements investigations to an ex-vivo situation by testing serum
      samples and found that the cytokine amounts measured was critically influenced by
      the actual kit used. The presented data indicate that statements regarding the
      quantitive determination of cytokines-and therefore their use as biomarkers-in
      serum samples have to be interpreted with caution.

PMID- 19578505
TI  - Useulness of B Natriuretic Peptides and Procalcitonin in Emergency Medicine.
AB  - Congestive heart failure (CHF) is the main cause of acute dyspnea in patients
      presented to an emergency department (ED), and it is associated with high
      morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide,
      released by ventricular myocytes directly proportional to wall tension, for
      lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP
      and the biologically inactive NT-proBNP have similar accuracy. Threshold values
      are higher in elderly population, and in patients with renal dysfunction. They
      might have also a prognostic value. Studies demonstrated that the use of BNP or
      NT-proBNP in dyspneic patients early in the ED reduced the time to discharge,
      total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours
      a day, because literature strongly suggests the beneficial impact of an early
      appropriate diagnosis and treatment in dyspneic patients.Etiologic diagnosis of
      febrile patients who present to an ED is complex and sometimes difficult.
      However, new evidence showed that there are interventions (including early
      appropriate antibiotics), which could reduce mortality rate in patients with
      sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C
      reactive protein. Thus, because of its excellent specificity and positive
      predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates
      ongoing and potentially severe systemic infection, which needs early antibiotics
      (e.g. meningitis). In lower respiratory tract infections, CAP or COPD
      exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic
      treatment duration.

PMID- 19578509
TI  - DICER1 and PRKRA in Colon Adenocarcinoma.
AB  - Differential microRNA expression in colon adenocarcinoma (CA) was previously
      reported. MicroRNA biogenesis and function requires a set of proteins designated
      as the microRNA machinery, which includes DICER1 and PRKRA. Loss of
      heterozygosity at 14q32.13 DICER1 locus was detected in up to 60% of CA cases.
      The in silico gene array analysis of CA showed down-regulation of DICER1 and an
      up-regulation of PRKRA. Immunohistochemically, DICER1 expression was abnormal in
      65% of CA (95 of 147 cases). PRKRA was deregulated in 70% of CA (32 of 46 cases).
      Expression of DICER1 and PRKRA was correlated with clinicopathologic features of
      CA. DICER1 up-regulation was seen more commonly in women. Only 10 of 46 cases
      immunostained for both DICER1 and PRKRA showed normal levels of both DICER1 and
      PRKRA. Microsatellite status of 32 cases was determined. Microsatellite instable
      cases showed DICER1 up-regulation more commonly when compared to microsatellite
      stable cases; however, this trend was not statistically significant. Abnormal
      DICER1 and/or PRKRA expression might explain the observed changes in microRNA
      profile. The status of the endogenous DICER1 and PRKRA in CA may help to predict
      the response to future RNA interference-based therapy.

PMID- 19578510
TI  - Biomarkers of Ovarian Reserve.
AB  - The primary function of the female ovary is the production of a mature and viable
      oocyte capable of fertilization and subsequent embryo development and
      implantation. At birth, the ovary contains a finite number of oocytes available
      for folliculogenesis. This finite number of available oocytes is termed "the
      ovarian reserve". The determination of ovarian reserve is important in the
      assessment and treatment of infertility. As the ovary ages, the ovarian reserve
      will decline. Infertility affects approximately 15%-20% of reproductive aged
      couples. The most commonly used biomarker assay to assess ovarian reserve is the
      measurement of follicle stimulating hormone (FSH) on day 3 of the menstrual
      cycle. However, anti-mullerian hormone and inhibin-B are other biomarkers of
      ovarian reserve that are gaining in popularity since they provide direct
      determination of ovarian status, whereas day 3 FSH is an indirect measurement.
      This review examines the physical tools and the hormone biomarkers used to
      evaluate ovarian reserve.

PMID- 19578511
TI  - Dendritic Cells Promoted by Ginseng Saponins Drive a Potent Th1 Polarization.
AB  - Dendritic cells (DC) play a pivotal role in the initiation of T-cell-mediated
      immune responses, making them an attractive cellular adjuvant for use in cancer
      vaccines. The interaction of T cells with DC is crucial for directing T cell
      differentiation towards the Th1, Th2 or Th17 type, and several factors
      determining the direction of the T cell polarization. IL-12 plays a central role
      in the immune system, not only by augmenting the cytotoxic activity of T cells
      and NK cells and regulating IFN-gamma production, but also by the capacity of IL
      12 to promote the development of Th1 cells. Therefore, it is important to
      identify factors that might affect the differentiation, maturation and function
      of DC. Ginseng is a medicinal herb widely used in Asian countries, and many of
      its pharmacological actions are attributed to the ginsenosides. Moreover, T
      cadinol and calamenene are sesquterpenes isolated from the heartwood of
      Cryptomeria japonica being pharmacologically active substances. We investigated
      whether M1 and M4, end products of steroidal ginseng saponins metabolized in
      digestive tracts, as well as T-cadinol and calamenene can drive DC maturation
      from human monocytes in vitro. Human monocytes were cultured with GM-CSF and IL-4
      for 6 days under standard conditions, followed by another 2 days in the presence
      of M1, M4, T-cadinol or calamenene. The expression levels of CD1a, CD80, CD83,
      CD86 and HLA-DR on M1-primed DC, M4-primed DC, T-cadinol-primed DC and calamenene
      primed DC were enhanced with a concomitant decrease in endocytic activity. M1
      primed DC, M4-primed DC, T-cadinol-primed DC or calamenene-primed DC enhanced the
      T cell stimulatory capacity in an allo MLR (allogeneic mixed lymphocyte
      reaction). Naive T cells co-cultured with allogeneic M1-primed DC, M4-primed DC,
      T-cadinol-primed DC or calamenene-primed DC turned into typical Th1 cells, which
      produced large quantities of IFN-gamma and released small amounts of IL-4
      depending on IL-12 secretion. In the CTL assay (cytotoxic T-lymphocyte assay),
      the production of IFN-gamma and (51)Cr release on M4-primed DC was more augmented
      than of immature DC or TNF-alpha-primed DC. These results suggest that M1, M4, T
      cadinol and calamenene appear to be a good factor to induce DC maturation, or
      even better in some respect, for the use in clinical DC therapy to induce strong
      Th1 type immune responses.

PMID- 19578512
TI  - A Rapid and Simple Bioassay Method for Herbicide Detection.
AB  - Chlamydomonas reinhardtii, a unicellular green alga, has been used in bioassay
      detection of a variety of toxic compounds such as pesticides and toxic metals,
      but mainly using liquid culture systems. In this study, an algal lawn-agar system
      for semi-quantitative bioassay of herbicidal activities has been developed.
      Sixteen different herbicides belonging to 11 different categories were applied to
      paper disks and placed on green alga lawns in Petri dishes. Presence of herbicide
      activities was indicated by clearing zones around the paper disks on the lawn 2-3
      days after application. The different groups of herbicides induced clearing zones
      of variable size that depended on the amount, mode of action, and chemical
      properties of the herbicides applied to the paper disks. This simple, paper-disk
      algal system may be used to detect the presence of herbicides in water samples
      and act as a quick and inexpensive semi-quantitative screening for assessing
      herbicide contamination.

PMID- 19578508
TI  - What is New on Thyroid Cancer Biomarkers.
AB  - Thyroid cancer harbours in about 5% of thyroid nodules. The majority of them are
      well-differentiated cancers originating from the follicular epithelium, and are
      subdivided into papillary and follicular carcinomas. Undifferentiated carcinomas
      and medullary thyroid carcinomas arising from C cells are less common.Although
      most thyroid nodules are benign, distinguishing thyroid cancer from benign
      lesions is crucial for an appropriate treatment and follow-up. The fine needle
      aspiration cytology (FNAC) allows the diagnosis of nature of thyroid nodules in
      the majority of cases. However, FNAC has some limitations, particularly in the
      presence of follicular lesions which can appear dubious in rare instances even at
      histology.In an effort to improve diagnostic accuracy and offer new prognostic
      criteria, several immunohistochemical and molecular markers have been proposed.
      However, most of them have to be validated on large series before being used in
      routine practice.

PMID- 19578513
TI  - Biomarkers and Bioassays for Cardiovascular Diseases: Present and Future.
AB  - Stratification of cardiac patients arriving at the emergency department is now
      being made according to the levels of acute cardiac biomarkers (i.e. cardiac
      troponin (cTn) or creatine kinase myocardial band (CK-MB)). Ongoing efforts are
      undertaken in an attempt to identify and validate additional cardiac biomarkers,
      for example, interleukin-6, soluble CD40L, and C-reactive protein, in order to
      further risk stratify patients with acute coronary syndrome. Several studies have
      also now shown an association of platelet transcriptome and genomic single
      nucleotide polymorphisms with myocardial infarction by using advanced genomic
      tools. A number of markers, such as myeloid-related protein 14 (MRP-14),
      cyclooxygenase-1 (COX-1), 5-lipoxygenase activating protein (FLAP), leukotriene
      A(4) hydrolase (LTA4H) and myocyte enhancing factor 2A (MEF2A), have been linked
      to acute coronary syndromes, including myocardial infarction. In the future,
      these novel markers may pave the way toward personalized disease-prevention
      programs based on a person's genomic, thrombotic and cardiovascular profiles.
      Current and future biomarkers and bioassays for identifying at-risk patients will
      be discussed in this review.

PMID- 19578514
TI  - MUC1 as a Putative Prognostic Marker for Prostate Cancer.
AB  - MUC1 is expressed on the apical surface of glandular epithelium. With functions
      including protection, adhesion and signaling, MUC1 has been implicated in
      prostate cancer. There are many splice variants, the best characterized of which
      are MUC1/1 and MUC1/2 which are determined by a SNP (rs4072037, 3506G>A).Blood
      DNA from the general population, BPH, sporadic and hereditary prostate cancer
      subjects were genotyped for the rs4072037 SNP. G allele frequencies were
      significantly reduced in hereditary prostate cancer (15%) compared to population,
      BPH or sporadic prostate cancer samples (27%, 39% and 26% respectively). In
      addition, the G allele was lost from 3 of 8 heterozygous sporadic prostate tumor
      samples compared to matched blood DNA. Bioinformatics analysis of MUC1 protein
      sequences provides insight into differences between the variants which may be
      functionally relevant. The literature indicates discrepancies between immuno
      histochemical studies, possibly due to the variety of MUC1 epitopes targeting
      diverse regions of the molecule. The contradictory findings in cell lines
      highlight the problem associated with inadequate experimental systems.This is the
      first report of genetic differences in MUC1 between blood and prostatic cancer
      tissue. This finding is important as proof of principle, given that many
      association studies focus on blood DNA rather than on the tumor DNA. As yet,
      potential functional differences between splice variants has been paid little
      attention. Antibodies which discriminate between the variants and standardization
      of methods would help to clarify whether there is a role for MUC1 as a prognostic
      marker.

PMID- 19578515
TI  - Alzheimer's Disease, Diagnosis and the Need for Biomarkers.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder of aging
      that presents with memory loss, disorientation, confusion and a reduction in
      cognitive ability. Although a definite diagnosis of the disorder can only be made
      post-mortem by histopathological analysis, a number of methods are currently
      available for the in vivo assessment of AD including psycho-metric tests and
      neuro-imaging. However, these clinical assessments are relatively nonspecific and
      imaging is very costly. Genetic testing can be performed if familial AD is
      suspected, although such cases represent a very small minority of total AD cases.
      Apolipoprotein E genotype provides a measure for analysing the risk of developing
      AD, but does not act as an absolute predictive biomarker for AD. Therefore there
      is a need for an accurate, universal, specific and cost-effective biomarker to
      facilitate not only ante-mortem diagnosis of AD, but also to allow progression of
      the disease and response to therapy to be monitored. This is the ultimate goal
      that our group is pursuing through the pan-European AddNeuroMed project.

PMID- 19578516
TI  - Proteomics Discovery of Disease Biomarkers.
AB  - Recent technological developments in proteomics have shown promising initiatives
      in identifying novel biomarkers of various diseases. Such technologies are
      capable of investigating multiple samples and generating large amount of data end
      points. Examples of two promising proteomics technologies are mass spectrometry,
      including an instrument based on surface enhanced laser desorption/ionization,
      and protein microarrays. Proteomics data must, however, undergo analytical
      processing using bioinformatics. Due to limitations in proteomics tools including
      shortcomings in bioinformatics analysis, predictive bioinformatics can be
      utilized as an alternative strategy prior to performing elaborate, high
      throughput proteomics procedures. This review describes mass spectrometry,
      protein microarrays, and bioinformatics and their roles in biomarker discovery,
      and highlights the significance of integration between proteomics and
      bioinformatics.

PMID- 19578517
TI  - Tracking Differential Gene Expression in MRL/MpJ Versus C57BL/6 Anergic B Cells:
      Molecular Markers of Autoimmunity.
AB  - BACKGROUND: Anergy is a key mechanism controlling expression of autoreactive B
      cells and a major site for failed regulation in autoimmune diseases. Yet the
      molecular basis for this differentiated cell state remains poorly understood. The
      current lack of well-characterized surface or molecular markers hinders the
      isolation of anergic cells for further study. Global gene profiling recently
      identified transcripts whose expression differentiates anergic from naive B cells
      in model mouse systems. The objective of the current study was to evaluate the
      molecular and cellular processes that differentiate anergic cells that develop in
      the healthy C57BL/6 (B6) milieu from those that develop in the autoimmune-prone
      MRL/MpJ (MRL) background. This approach takes advantage of B6 and MRL mice
      bearing an anti-laminin Ig transgene with a well characterized anergic B cell
      phenotype. RESULTS: Global gene expression was evaluated in purified transgenic B
      cells using Operon version 3.0 oligonucleotide microarray assaying >31,000
      oligoprobes. Genes with a 2-fold expression difference in B6 as compared to MRL
      anergic B cells were identified. Expression of selected genes was confirmed using
      quantitative RT-PCR. This approach identified 43 probes corresponding to 37
      characterized genes, including Ptpn22, CD74, Birc1f/Naip, and Ctla4, as
      differentially expressed in anergic B cells in the two strains. Gene Ontology
      classification identified differentiation, cell cycle, proliferation,
      development, apoptosis, and cell death as prominently represented ontology
      groups. Ingenuity Pathway Analysis identified two major networks incorporating 27
      qualifying genes. Network 1 centers on beta-estradiol and TP53, and Network 2
      encompasses RB1, p38 MAPK, and NFkB cell growth, proliferation, and cell cycle
      signaling pathways. CONCLUSION: Using microarray analysis we identified 37
      characterized genes and two functional pathways engaged in maintenance of B cell
      anergy for which expression is distorted by underlying autoimmune genetic
      susceptibility. This approach identifes a new biological role for multiple genes
      and potential new therapeutic targets in autoimmunity.

PMID- 19578518
TI  - Activation of Tissue Remodeling Precedes Obliterative Bronchiolitis in Lung
      Transplant Recipients.
AB  - Obliterative bronchiolitis (OB) and Bronchiolitis Obliterans Syndrome (BOS) are
      frequent complications in the lung transplant recipient, and are the leading
      cause of mortality after transplantation. The mechanisms responsible for OB
      remain elusive, but inflammatory and tissue remodeling responses are implicated.
      We hypothesized that alterations in markers of tissue remodeling in BALF of lung
      transplant recipients could predict development of OB. To test this, we
      identified 13 lung transplant recipients who developed both BOS and histologic OB
      (OB group) at median post-operative day (POD) 485 (range 73-2070).
      Bronchoalveolar lavage fluid (BALF) was obtained at median POD 387 (range 45
      2205), which preceded the onset of OB and BOS by a median of 140 days (range 60
      365). As a control, BALF was also obtained from a group of 21 stable recipients
      without OB (non-OB group) at median POD 335 (range 270-395). BALF was examined
      for gelatinolytic activity, fibronectin gene transcription, and transforming
      growth factor-beta1 (TGF-beta1) expression. Gelatin zymography of BALF from the
      OB group showed increased matrix metalloproteinase-9 (MMP-9) activity over that
      of the non-OB group (p < 0.005). Similarly, BALF from the OB group induced
      greater fibronectin expression in fibroblasts compared to the non-OB group (p <
      0.03). The induction of fibronectin also correlated with the amount of TGF-beta1
      protein in BALF (r = 0.71) from the OB group. We conclude that activation of
      tissue remodeling precedes the onset of OB, and analysis of gelatinolytic and/or
      fibronectin-inducing activity in BALF can serve as an early, pre-clinical marker
      for OB.

PMID- 19578519
TI  - Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A
      Prospective Study in a Population at Risk.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related death
      in Europe and its prognosis is largely dependent on stage at diagnosis.
      Currently, there are no suitable tumour markers for early detection of CRC. In a
      retrospective study we previously found discriminative CRC serum protein profiles
      with surface enhanced laser desorption ionisation-time of flight mass
      spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these
      profiles. Additionally, we assessed their applicability for follow-up after
      surgery and investigated tissue protein profiles of patients with CRC and
      adenomatous polyps (AP). Serum and tissue samples were collected from patients
      without known malignancy with an indication for colonoscopy and patients with AP
      and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients
      with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52)
      and CRC (n = 47) were analysed as described previously. Peak intensities were
      compared by non-parametric testing. Discriminative power of differentially
      expressed proteins was assessed with support vector machines (SVM). We confirmed
      the decreased serum levels of apolipoprotein C-1 in CRC in the current
      population. No differences were observed between CON and AP. Apolipoprotein C-I
      levels did not change significantly within 1 month post-surgery, although a
      gradual return to normal levels was observed. Several proteins differed between
      AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1.
      This peak was increased in CRC compared to AP. Although we prospectively
      validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles
      did not yield SVM classifiers with suitable sensitivity and specificity for
      classification of our patient groups.

PMID- 19578520
TI  - Effects of Cyclooxygenase Inhibitors on Apoptotic Neuroretinal Cells.
AB  - Glaucoma is characterized by a loss of retinal ganglion cells (RGC) which is
      associated with a decrease of visual function. Neuroprotective agents as a new
      therapeutic strategy could prevent the remaining neurons from apoptotic cell
      death. Previous studies have shown the involvement of the Cyclooxygenase (COX)-2
      signalling in the apoptotic death of neurons. Herein we investigated the
      neuroprotective effect of COX-1/COX-2- and selective COX-2- inhibitors on
      apoptotic. R28, a neuroretinal cell line and determined the PGE(2) levels by
      ELISA. Furthermore we investigated differences in protein expression in the cells
      after exposure to elevated pressure compared to untreated cells by ProteinChip
      analysis.In addition, a protein profiling study of the cells after exposure to
      elevated pressure was performed. The protein expression profiles were measured by
      SELDI-TOF (Surface Enhanced Laser Desorption/Ionization-time of flight) Protein
      Chips. The protein identification was performed by mass spectrometry (MS).It
      could be shown that COX-2 inhibition significantly prevented the cells from
      apoptosis and reduced the PGE(2) concentrations. Selective COX-2 inhibitors were
      significant more potent than non-selective inhibitors or COX-1 inhibitors. We
      found differently expressed protein patterns in neuroretinal cells cultured at
      atmospheric pressure compared to those cells exposed to elevated pressure with or
      without celecoxib respectively. We identified three biomarkers, ubiquitin, HSP10
      and NDKB, which were differently expressed in the groups. However, our data
      indicates a distinct neuroprotective effect of COX-2 inhibition. The local
      treatment with selective COX-2 inhibitors might provide an innovative strategy of
      therapeutic intervention for glaucoma.

PMID- 19578521
TI  - Hematopoietic Lineage Transcriptome Stability and Representation in PAXgene
      Collected Peripheral Blood Utilising SPIA Single-Stranded cDNA Probes for
      Microarray.
AB  - Peripheral blood as a surrogate tissue for transcriptome profiling holds great
      promise for the discovery of diagnostic and prognostic disease biomarkers,
      particularly when target tissues of disease are not readily available. To
      maximize the reliability of gene expression data generated from clinical blood
      samples, both the sample collection and the microarray probe generation methods
      should be optimized to provide stabilized, reproducible and representative gene
      expression profiles faithfully representing the transcriptional profiles of the
      constituent blood cell types present in the circulation. Given the increasing
      innovation in this field in recent years, we investigated a combination of
      methodological advances in both RNA stabilisation and microarray probe generation
      with the goal of achieving robust, reliable and representative transcriptional
      profiles from whole blood. To assess the whole blood profiles, the transcriptomes
      of purified blood cell types were measured and compared with the global
      transcriptomes measured in whole blood. The results demonstrate that a
      combination of PAXgene() RNA stabilising technology and single-stranded cDNA
      probe generation afforded by the NuGEN Ovation RNA amplification system V2()
      enables an approach that yields faithful representation of specific hematopoietic
      cell lineage transcriptomes in whole blood without the necessity for prior sample
      fractionation, cell enrichment or globin reduction. Storage stability assessments
      of the PAXgene() blood samples also advocate a short, fixed room temperature
      storage time for all PAXgene() blood samples collected for the purposes of global
      transcriptional profiling in clinical studies.

PMID- 19578522
TI  - Serum Concentrations of F2-Isoprostanes and 4-Hydroxynonenal in Hemodialysis
      Patients in Relation to Inflammation and Renal Anemia.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing hemodialysis
      (HD) are apparently exposed to enhanced oxidative stress and to inflammation. It
      was the aim of this study to characterize the state of systemic oxidative stress
      of ESRD patients before and following HD using highly specific biomarkers, F(2)
      isoprostanes and 4-hydroxynonenal (HNE). Furthermore the question should be
      answered, if there are associations between inflammation and systemic oxidative
      stress and/or between systemic oxidative stress and renal anemia, which is more
      or less typical for HD patients. PATIENTS AND METHODS: Concentrations of F(2)
      isoprostanes, HNE, C-reactive protein (CRP) as marker of inflammation, and
      hemoglobin were measured in serum samples of patients with ESRD before and after
      HD and of healthy control persons for comparison. Total (esterified plus free)
      F(2)-isoprostanes were quantified by highly sensitive gas chromatography/mass
      spectrometry technique, HNE by thin layer chromatography and HPLC/UV detection,
      CRP by immunoturbidimetry and hemoglobin by clinico-chemical routine assay.
      RESULTS: 1. HD patients showed significantly higher serum concentrations of F(2)
      isoprostanes and HNE than healthy human control subjects. 2. Total (esterified
      plus free) F(2)-isoprostane levels before HD were not significantly different
      from those after HD, whereas HNE levels were significantly decreased in patients
      after HD. 3. F(2)-isoprostane concentrations in HD patients correlated with the
      levels of CRP, whereas HNE concentrations inversely correlated with the content
      of hemoglobin. CONCLUSION: Both, F(2)-isoprostanes and HNE serum concentrations
      are useful oxidative stress parameters in ESRD patients undergoing HD. Whereas
      HNE strongly correlates with the severity of renal anemia, leading to left heart
      insufficiency, F(2)-isoprostanes (sum of free plus esterified) highly correlate
      with the degree of inflammation.

PMID- 19578523
TI  - Clinical Performance of a Salivary Amylase Activity Monitor During Hemodialysis
      Treatment.
AB  - The hemodialysis procedure is thought to be a physical stressor in the majority
      of hemodialyzed patients. Previous studies suggest that elevated salivary amylase
      level may correlate with increased plasma norepinephrine level under
      psychological and physical stress conditions. In this study, we investigated
      biological stress reactivity during hemodialysis treatment using salivary amylase
      activity as a biomarker. Seven patients (male/female = 5/2, age: 67.7+/-5.9
      years) who had been receiving regular 4 h hemodialysis were recruited. Salivary
      amylase activity was measured using a portable analyzer every hour during the
      hemodialysis session. Salivary amylase activity was shown to be relatively stable
      and constant throughout hemodialysis, whereas there were significant changes in
      systolic blood pressure and pulse rate associated with blood volume reduction.
      Our results show that hemodialysis treatment per se dose not affect salivary
      amylase activity.

PMID- 19578524
TI  - Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen.
AB  - Carcinoembryonic antigen (CEA), highly expressed in many cancer types, is an
      important target for cancer diagnosis and therapy. Radionuclide-based imaging
      techniques (gamma camera, single photon emission computed tomography [SPECT] and
      positron emission tomography [PET]) have been extensively explored for CEA
      targeted cancer imaging both preclinically and clinically. Briefly, these studies
      can be divided into three major categories: antibody-based, antibody fragment
      based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the
      earliest among the three categories, typically gave suboptimal tumor contrast due
      to the prolonged circulation life time of intact antibodies. Subsequently, a
      number of engineered anti-CEA antibody fragments (e.g. Fab', scFv, minibody,
      diabody and scFv-Fc) have been labeled with a variety of radioisotopes for CEA
      imaging, many of which have entered clinical investigation. CEA-Scan (a (99m)Tc
      labeled anti-CEA Fab' fragment) has already been approved by the United States
      Food and Drug Administration for cancer imaging. Meanwhile, pretargeting
      strategies have also been developed for CEA imaging which can give much better
      tumor contrast than the other two methods, if the system is designed properly. In
      this review article, we will summarize the current state-of-the-art of
      radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short
      half-lives (e.g. (18)F and (99m)Tc) are more suitable for labeling small
      engineered antibody fragments while the isotopes with longer half-lives (e.g.
      (123)I and (111)In) are needed for antibody labeling to match its relatively long
      circulation half-life. With further improvement in tumor targeting efficacy and
      radiolabeling strategies, novel CEA-targeted agents may play an important role in
      cancer patient management, paving the way to "personalized medicine".

PMID- 19578525
TI  - Biomarkers in Acute Coronary Syndrome.
AB  - BACKGROUND: Evaluation of patients who present to the hospital with acute
      undifferentiated chest pain or other symptoms and signs suggestive of Acute
      Coronary Syndrome (ACS) is often a clinical challenge. The initial assessment,
      requiring a focused history (including risk factors analysis), a physical
      examination, an electrocardiogram (EKG) and serum cardiac marker determination,
      is time-consuming and troublesome. Recent investigations have indicated that
      increases in biomarkers of necrosis, inflammation, ischemia and myocardial
      stretch may provide earlier assessment of overall patient risk, help in
      identifying the adequate diagnostic and therapeutic management for each patient
      and allow for prevention of substantial numbers of new events. APPROACH AND
      CONTENT: The purpose of this review is to provide an overview of the
      characteristics of several biomarkers that may have potential clinical utility to
      identify ACS patients. Patho-physiology, analytical and clinical characteristics
      have been evaluated for each marker, underlying the properties for potential
      routine clinical use. SUMMARY: The biomarkers discussed in this review are
      promising and might lead to improved diagnosis and risk stratification of
      patients with ACS, however their clinical application requires further studies.
      It is important to define their clinical role as diagnostic markers, their
      predictive value and the specificity, standardization and detection limits of the
      assays.

PMID- 19578527
TI  - Smokefree environments in Latin America: on the road to real change?
AB  - Latin American countries are experiencing an increasing burden of tobacco-related
      diseases. Smoke free policies are cost-effective interventions to control both
      exposure of nonsmokers to the toxic chemicals in secondhand tobacco smoke and to
      reduce the prevalence of smoking and its consequent morbidity and mortality. The
      World Health Organization Framework Convention on Tobacco Control has created
      momentum in Latin America to implement meaningful tobacco control policies. As of
      August 2007, Uruguay, two provinces and three cities in Argentina, and one state
      in Venezuela, had passed, regulated, and enforced 100% smokefree legislation. The
      tobacco industry, working through local subsidiaries, has been the strongest
      obstacle in achieving this goal and has prevented progress elsewhere in the
      region. During the 1990s, transnational tobacco companies Philip Morris
      International and British American Tobacco developed voluntary initiatives
      ("Courtesy of Choice" and "Environmental Tobacco Smoke Consultancy" programs) to
      prevent effective smokefree policies. Another important barrier in the region has
      often been a weak and fragmented local civil society. Opportunities in the region
      that should be taken into account are a high public support for smokefree
      environments and increasing capacity building available from international
      collaboration on tobacco control. Policymakers and tobacco control advocates
      should prioritize the implementation of smokefree policies in Latin America to
      protect nonsmokers, reduce smoking prevalence with its economic and disease
      burden in the region.

PMID- 19578526
TI  - Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by
      proteomic studies of animal models.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      affects motor neurons and causes progressive muscle weakness and atrophy. The
      etiology and pathogenesis of ALS are largely unknown and no effective treatment
      is presently available. About 10% of patients have the familial or inherited form
      of the disease (fALS), among which 20% is linked to mutations with Cu(2+)/Zn(2+)
      superoxide dismutase (mSOD1). Transgenic animals expressing human mSOD1 are
      excellent models for understanding not only fALS but sporadic ALS as well.
      Pathological features in both ALS patients and mSOD1 transgenic animals' spinal
      cords share commonalties including the accumulation of misfolded protein
      inclusions. Recent proteomic investigations on ALS animal models have discovered
      alterations in protein expression, protein-protein interactions and post
      translational modifications. These efforts have revealed aspects of potential
      pathogenic mechanisms and identified probable therapeutic targets. The present
      review summarizes the major findings of proteomics studies performed on the mSOD1
      mice with particular emphasis on the spinal cord proteome. These results are
      compared with those reported using cell cultures or specimens obtained from ALS
      patients. The convergence of pathogenic processes on protein chaperone function,
      and its relationship to protein degradation, metabolic dysfunction and oxidative
      signaling events is discussed.

PMID- 19578528
TI  - 14-Month-Old Infants Form Novel Word-Spatial Relation Associations.
AB  - This study explored 14-month-old infants' ability to form novel word-spatial
      relation associations. During habituation, infants heard 1 novel word (e.g.,
      teek) while viewing dynamic containment events (i.e., Big Bird placed in a box)
      and, on other habituation trials, a second novel word (e.g., blick) while viewing
      dynamic support events (i.e., Big Bird placed on the box). Each novel word was
      presented in a sentence (e.g., "She's putting Big Bird teek the box"). During the
      test, infants discriminated an event that maintained the habituation word
      relation pairing from one that presented a switch in this pairing. The results
      indicate that 14-month-olds can learn to form word-relation associations quickly,
      requiring only a few minutes of experience with each word-relation pairing.

PMID- 19578529
TI  - Refining the Conceptualization of an Important Future-Oriented Self-Regulatory
      Behavior: Proactive Coping.
AB  - Proactive coping, directed at an upcoming as opposed to an ongoing stressor, is a
      new focus in positive psychology research. However, two differing
      conceptualizations of this construct create confusion. This study compared how
      each operationalization of proactive coping relates to well-being. Participants
      (N = 281) facing an upcoming college examination completed the Proactive Coping
      Inventory (PCI; consisting of two subscales that each assess one of the
      conceptualizations), the Proactive Competence Scale (PCS; that assesses the
      proactive coping process), and measures of well-being. The results demonstrated
      that conceptualizing proactive coping as a positively-focused striving for goals
      was predictive of well-being (the shared variance from affect, subjective well
      being and physical symptoms), whereas conceptualizing proactive coping as focused
      on preventing a negative future was not. The first conceptualization of proactive
      coping's unique association with well-being was explained by two of the proactive
      competencies, use of resources and realistic goal setting, and the remaining
      variance in well-being was explained by the first factor of optimism. These
      results demonstrated that aspiring for a positive future is distinctly predictive
      of well-being and that research should focus on accumulating resources and goal
      setting in designing interventions to promote proactive coping.

PMID- 19578530
TI  - The environmental dimensions of the HIV/AIDS pandemic: a call for scholarship and
      evidence-based intervention.
AB  - The HIV/AIDS pandemic has had dramatic influence on the demographic dynamics of
      many of the world's less economically developed regions. Today, an estimated 33
      million individuals are living with HIV, and recent data suggest that, every day,
      over 6800 persons become HIV-infected and over 5700 persons die from AIDS (UNAIDS
      2006). The age profile of HIV infection is well known, with new cases impacting
      primarily prime-age adults. Sub-Saharan Africa remains the world's most affected
      region with recent population-based surveys suggesting that adult prevalence
      rates (age 15-49) reaches as high as 25% in Botswana and over 23% in Lesotho
      (UNAIDS 2006). Still, HIV/AIDS also impacts children, with over 2 million HIV+
      individuals under age 15 in sub-Saharan Africa; And the disease profile now
      includes many individuals over age 50 due to the positive impact on life
      expectancy of recent treatment advances (UNAIDS 2006).Of course, HIV/AIDS'
      impacts at the individual and household levels are difficult to discern from
      aggregate data although ethnographic research provides insights into nuanced
      household survival strategies (e.g., Evans 2005; Schatz and Ogunmefun 2007). Such
      work reveals household efforts to maintain a sense of "normality" in response to
      the impacts of HIV/AIDS, otherwise known as "the disease" (Bohman et al. 2007).

PMID- 19578531
TI  - Regioselectivity of Pictet-Spengler Cyclization Reactions to Construct the
      Pentacyclic Frameworks of the Ecteinascidin-Saframycin Class of
      Tetrahydroisoquinoline Antitumor Antibiotics.
AB  - The regiochemical outcome of Pictet-Spengler cyclization reactions directed
      toward the preparation of the pentacyclic core of the ecteinascidin class of
      antitumor antibiotics has been investigated on two different phenolic substrates.
      In one substrate, the assistance of an incipient benzylamine group at C-4 is
      postulated to direct the cyclization in favor of the pentacyclic framework of ET
      743, which bears a hydroxyl group at C-18. Conversely, cyclization of an
      alternative substrate lacking a heteroatom at C-4 favors the opposite
      regiochemical outcome, primarily affording an unnatural pentacyclic core bearing
      a hydroxyl group at C-16.

PMID- 19578532
TI  - Peculiarities of the continuous glucose monitoring data stream and their impact
      on developing closed-loop control technology.
AB  - Therapeutic advances in type 1 diabetes (T1DM) are currently focused on
      developing a closed-loop control system using a continuous glucose monitor (CGM),
      subcutaneous insulin delivery, and a control algorithm. Because a CGM assesses
      blood glucose indirectly (and therefore often inaccurately), it limits the
      effectiveness of the controller. In order to improve the quality of CGM data, a
      series of analyses are suggested. These analyses evaluate and compensate for CGM
      errors, assess risks associated with glucose variability, predict glucose
      fluctuation, and forecast hypo- and hyperglycemia. These analyses are illustrated
      with data collected using the MiniMed CGMS(r) (Medtronic, Northridge, CA) and
      Freestyle Navigator(TM) (Abbott Diabetes Care, Alameda, CA). It is important to
      remember that traditional statistics do not work with CGM data because
      consecutive CGM readings are highly interdependent.

PMID- 19578533
TI  - Efficient Hybrid EM for Linear and Nonlinear Mixed Effects Models with Censored
      Response.
AB  - Medical laboratory data are often censored, due to limitations of the measuring
      technology. For pharmacokinetics measurements and dilution-based assays, for
      example, there is a lower quantification limit, which depends on the type of
      assay used. The concentration of HIV particles in the plasma is subject to both
      lower and upper quantification limit. Linear and nonlinear mixed effects models,
      which are often used in these types of medical applications, need to be able to
      deal with such data issues. In this paper we discuss a hybrid Monte Carlo and
      numerical integration EM algorithm for computing the maximum likelihood estimates
      for linear and non-linear mixed models with censored data. Our implementation
      uses an efficient block-sampling scheme, automated monitoring of convergence, and
      dimension reduction based on the QR decomposition. For clusters with up to two
      censored observations numerical integration is used instead of Monte Carlo
      simulation. These improvements lead to a several-fold reduction in computation
      time. We illustrate the algorithm using data from an HIV/AIDS trial. The Monte
      Carlo EM is evaluated and compared with existing methods via a simulation study.

PMID- 19578534
TI  - A method of external fixation to offload and protect the foot following
      reconstruction in high-risk patients: the SALSAstand.
AB  - INTRODUCTION: The course of wound healing in high-risk patients with diabetes,
      particularly those with peripheral arterial disease and renal failure, is often
      prolonged and fraught with complications. Traditional methods of offloading the
      posterior foot or holding correction in place following diabetic foot
      reconstruction include various padded and bolstering devices. METHODS: In this
      article, we describe a method (SALSAstand) to effectively elevate, offload, and
      protect the foot with an external fixation device, while also promoting flap
      healing, maintaining tendon correction, and limiting the tendon retraction and
      contracture that is commonly seen following a foot-salvage procedure in high-risk
      patients. RESULTS: Not applicable. DISCUSSION: The SALSAstand device has been
      successfully utilized on many patients in our service to accomplish the
      aforementioned goals in this most challenging patient population.

PMID- 19578536
TI  - Precocious locomotor behavior begins in the egg: development of leg muscle
      patterns for stepping in the chick.
AB  - BACKGROUND: The chicken is capable of adaptive locomotor behavior within hours
      after hatching, yet little is known of the processes leading to this precocious
      skill. During the final week of incubation, chick embryos produce distinct
      repetitive limb movements that until recently had not been investigated. In this
      study we examined the leg muscle patterns at 3 time points as development of
      these spontaneous movements unfolds to determine if they exhibit attributes of
      locomotion reported in hatchlings. We also sought to determine whether the deeply
      flexed posture and movement constraint imposed by the shell wall modulate the
      muscle patterns. METHODOLOGY/PRINCIPAL FINDINGS: Synchronized electromyograms for
      leg muscles, force and video were recorded continuously from embryos while in
      their naturally flexed posture at embryonic day (E) 15, E18 and E20. We tested
      for effects of leg posture and constraint by removing shell wall anterior to the
      foot. Results indicated that by E18, burst onset time distinguished leg muscle
      synergists from antagonists across a 10-fold range in burst frequencies (1-10
      Hz), and knee extensors from ankle extensors in patterns comparable to locomotion
      at hatching. However, burst durations did not scale with step cycle duration in
      any of the muscles recorded. Despite substantially larger leg movements after
      shell removal, the knee extensor was the only muscle to vary its activity, and
      extensor muscles often failed to participate. To further clarify if the
      repetitive movements are likely locomotor-related, we examined bilateral
      coordination of ankle muscles during repetitive movements at E20. In all cases
      ankle muscles exhibited a bias for left/right alternation.
      CONCLUSIONS/SIGNIFICANCE: Collectively, the findings lead us to conclude that the
      repetitive leg movements in late stage embryos are locomotor-related and a
      fundamental link in the establishment of precocious locomotor skill. The
      potential importance of differences between embryonic and posthatching locomotion
      is discussed.

PMID- 19578538
TI  - Pulse wave analysis in normal pregnancy: a prospective longitudinal study.
AB  - BACKGROUND: Outside pregnancy, arterial pulse wave analysis provides valuable
      information in hypertension and vascular disease. Studies in pregnancy using this
      technique show that vascular stiffness is raised in women with established pre
      eclampsia. We aimed to establish normal ranges for parameters of pulse wave
      analysis in normal pregnancy and to compare different ethnic groups.
      METHODOLOGY/PRINCIPAL FINDINGS: This prospective study was conducted at The
      Homerton University Hospital, London between January 2006 and March 2007. Using
      applanation tonometry, the radial artery pulse waveform was recorded and the
      aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at
      heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated. We
      recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia
      (n = 24, 3.6%) or gestational hypertension (n = 36, 5.4%) were excluded. We also
      excluded 47 women with other pregnancy complications or incomplete follow-up,
      leaving 541 healthy normotensive pregnant women for subsequent analysis. In the
      overall group of 541 women, there were no significant changes in AP or AIx-75 as
      pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell
      significantly from the first to the second trimester, then rose again in the
      third (P<0.001). The two main ethnic groups represented were Caucasian (n = 229)
      and Afrocaribbean (n = 216). There were no significant differences in AP or AIx
      75 in any trimester between these two ethnic groups. CONCLUSIONS: This study is
      the largest to date of pulse wave analysis in normal pregnancy, the first to
      report on a subset of women studied longitudinally, and the first to investigate
      the effect of ethnicity. These data provide the foundation for further
      investigation into the potential role of this technique in vascular disorders in
      pregnancy.

PMID- 19578537
TI  - Modulation of gene expression in Actinobacillus pleuropneumoniae exposed to
      bronchoalveolar fluid.
AB  - BACKGROUND: Actinobacillus pleuropneumoniae, the causative agent of porcine
      contagious pleuropneumonia, is an important pathogen of swine throughout the
      world. It must rapidly overcome the innate pulmonary immune defenses of the pig
      to cause disease. To better understand this process, the objective of this study
      was to identify genes that are differentially expressed in a medium that mimics
      the lung environment early in the infection process. METHODS AND PRINCIPAL
      FINDINGS: Since bronchoalveolar lavage fluid (BALF) contains innate immune and
      other components found in the lungs, we examined gene expression of a virulent
      serovar 1 strain of A. pleuropneumoniae after a 30 min exposure to BALF, using
      DNA microarrays and real-time PCR. The functional classes of genes found to be up
      regulated most often in BALF were those encoding proteins involved in energy
      metabolism, especially anaerobic metabolism, and in cell envelope, DNA, and
      protein biosynthesis. Transcription of a number of known virulence genes
      including apxIVA and the gene for SapF, a protein which is involved in resistance
      to antimicrobial peptides, was also up-regulated in BALF. Seventy-nine percent of
      the genes that were up-regulated in BALF encoded a known protein product, and of
      these, 44% had been reported to be either expressed in vivo and/or involved in
      virulence. CONCLUSIONS: The results of this study suggest that in early stages of
      infection, A. pleuropneumoniae may modulate expression of genes involved in
      anaerobic energy generation and in the synthesis of proteins involved in cell
      wall biogenesis, as well as established virulence factors. Given that many of
      these genes are thought to be expressed in vivo or involved in virulence,
      incubation in BALF appears, at least partially, to simulate in vivo conditions
      and may provide a useful medium for the discovery of novel vaccine or therapeutic
      targets.

PMID- 19578539
TI  - Conserved amino acid sequence features in the alpha subunits of MoFe, VFe, and
      FeFe nitrogenases.
AB  - BACKGROUND: This study examines the structural features and phylogeny of the
      alpha subunits of 69 full-length NifD (MoFe subunit), VnfD (VFe subunit), and
      AnfD (FeFe subunit) sequences. METHODOLOGY/PRINCIPAL FINDINGS: The analyses of
      this set of sequences included BLAST scores, multiple sequence alignment,
      examination of patterns of covariant residues, phylogenetic analysis and
      comparison of the sequences flanking the conserved Cys and His residues that
      attach the FeMo cofactor to NifD and that are also conserved in the alternative
      nitrogenases. The results show that NifD nitrogenases fall into two distinct
      groups. Group I includes NifD sequences from many genera within Bacteria,
      including all nitrogen-fixing aerobes examined, as well as strict anaerobes and
      some facultative anaerobes, but no archaeal sequences. In contrast, Group II NifD
      sequences were limited to a small number of archaeal and bacterial sequences from
      strict anaerobes. The VnfD and AnfD sequences fall into two separate groups, more
      closely related to Group II NifD than to Group I NifD. The pattern of perfectly
      conserved residues, distributed along the full length of the Group I and II NifD,
      VnfD, and AnfD, confirms unambiguously that these polypeptides are derived from a
      common ancestral sequence. CONCLUSIONS/SIGNIFICANCE: There is no indication of a
      relationship between the patterns of covariant residues specific to each of the
      four groups discussed above that would give indications of an evolutionary
      pathway leading from one type of nitrogenase to another. Rather the totality of
      the data, along with the phylogenetic analysis, is consistent with a radiation of
      Group I and II NifDs, VnfD and AnfD from a common ancestral sequence. All the
      data presented here strongly support the suggestion made by some earlier
      investigators that the nitrogenase family had already evolved in the last common
      ancestor of the Archaea and Bacteria.

PMID- 19578540
TI  - Structure-function analysis of nucleolin and ErbB receptors interactions.
AB  - BACKGROUND: The ErbB receptor tyrosine kinases and nucleolin are major
      contributors to malignant transformation. Recently we have found that cell
      surface ErbB receptors interact with nucleolin via their cytoplasmic tail.
      Overexpression of ErbB1 and nucleolin leads to receptor phosphorylation,
      dimerization and anchorage independent growth. METHODOLOGY/PRINCIPAL FINDINGS: In
      the present study we explored the regions of nucleolin and ErbB responsible for
      their interaction. Using mutational analyses, we addressed the structure-function
      relationship of the interaction between ErbB1 and nucleolin. We identified the
      ErbB1 nuclear localization domain as nucleolin interacting region. This region is
      important for nucleolin-associated receptor activation. Notably, though the
      tyrosine kinase domain is important for nucleolin-associated receptor activation,
      it is not involved in nucleolin/ErbB interactions. In addition, we demonstrated
      that the 212 c-terminal portion of nucleolin is imperative for the interaction
      with ErbB1 and ErbB4. This region of nucleolin is sufficient to induce ErbB1
      dimerization, phosphorylation and growth in soft agar. CONCLUSIONS/SIGNIFICANCE:
      The oncogenic potential of ErbB depends on receptor levels and activation.
      Nucleolin affects ErbB dimerization and activation leading to enhanced cell
      growth. The C-terminal region of nucleolin and the ErbB1 NLS-domain mediate this
      interaction. Moreover, when the C-terminal 212 amino acids region of nucleolin is
      expressed with ErbB1, it can enhance anchorage independent cell growth. Taken
      together these results offer new insight into the role of ErbB1 and nucleolin
      interaction in malignant cells.

PMID- 19578541
TI  - Hair sheep blood, citrated or defibrinated, fulfills all requirements of blood
      agar for diagnostic microbiology laboratory tests.
AB  - BACKGROUND: Blood agar is used for the identification and antibiotic
      susceptibility testing of many bacterial pathogens. In the developing world,
      microbiologists use human blood agar because of the high cost and inhospitable
      conditions for raising wool sheep or horses to supply blood. Many pathogens
      either fail to grow entirely or exhibit morphologies and hemolytic patterns on
      human blood agar that confound colony recognition. Furthermore, human blood can
      be hazardous to handle due to HIV and hepatitis. This study investigated whether
      blood from hair sheep, a hardy, low-maintenance variety of sheep adapted for hot
      climates, was suitable for routine clinical microbiology studies. METHODS AND
      FINDINGS: Hair sheep blood obtained by jugular venipuncture was anticoagulated by
      either manual defibrination or collection in human blood bank bags containing
      citrate-phosphate-dextrose. Trypticase soy 5% blood agar was made from both forms
      of hair sheep blood and commercial defibrinated wool sheep blood. Growth
      characteristics, colony morphologies, and hemolytic patterns of selected human
      pathogens, including several streptococcal species, were evaluated. Specialized
      identification tests, including CAMP test, reverse CAMP test, and satellite
      colony formation with Haemophilus influenzae and Abiotrophia defectiva were also
      performed. Mueller-Hinton blood agar plates prepared from the three blood types
      were compared in antibiotic susceptibility tests by disk diffusion and E-test.
      CONCLUSIONS: The results of all studies showed that blood agar prepared from
      citrated hair sheep blood is suitable for microbiological tests used in routine
      identification and susceptibility profiling of human pathogens. The validation of
      citrated hair sheep blood eliminates the labor-intensive and equipment-requiring
      process of manual defibrination. Use of hair sheep blood, in lieu of human blood
      currently used by many developing world laboratories and as an alternative to
      cost-prohibitive commercial sheep blood, offers the opportunity to dramatically
      improve the safety and accuracy of laboratory diagnosis of pathogenic bacteria in
      resource-poor countries.

PMID- 19578542
TI  - A conserved ethylene biosynthesis enzyme leads to andromonoecy in two cucumis
      species.
AB  - Andromonoecy is a widespread sexual system in angiosperms, characterized by
      plants carrying both male and bisexual flowers. Monoecy is characterized by the
      presence of both male and female flowers on the same plant. In cucumber, these
      sexual forms are controlled by the identity of the alleles at the M locus. In
      melon, we recently showed that the transition from monoecy to andromonoecy result
      from a mutation in 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene,
      CmACS-7. To isolate the andromonoecy gene in cucumber we used a candidate gene
      approach in combination with genetical and biochemical analysis. We demonstrated
      co-segregation of CsACS2, a close homolog of CmACS-7, with the M locus. Sequence
      analysis of CsACS2 in cucumber accessions identified four CsACS2 isoforms, three
      in andromonoecious and one in monoecious lines. To determine whether the
      andromonoecious phenotype is due to a loss of ACS enzymatic activity, we
      expressed the four isoforms in Escherichia coli and assayed their activity in
      vitro. Like in melon, the isoforms from the andromonoecious lines showed reduced
      to no enzymatic activity and the isoform from the monoecious line was active.
      Consistent with this, the mutations leading andromonoecy were clustered in the
      active site of the enzyme. Based on this, we concluded that active CsACS2 enzyme
      leads to the development of female flowers in monoecious lines, whereas a
      reduction of enzymatic activity yields hermaphrodite flowers. Consistent with
      this, CsACS2, like CmACS-7 in melon, is expressed specifically in carpel
      primordia of buds determined to develop carpels. Following ACS expression, inter
      organ communication is likely responsible for the inhibition of stamina
      development. In both melon and cucumber, flower unisexuality seems to be the
      ancestral situation, as the majority of Cucumis species are monoecious. Thus, the
      ancestor gene of CmACS-7/CsACS2 likely have controlled the stamen development
      before speciation of Cucumis sativus (cucumber) and Cucumis melo (melon) that
      have diverged over 40 My ago. The isolation of the genes for andromonoecy in
      Cucumis species provides a molecular basis for understanding how sexual systems
      arise and are maintained within and between species.

PMID- 19578543
TI  - Interactions between beta subunits of the KCNMB family and Slo3: beta4
      selectively modulates Slo3 expression and function.
AB  - BACKGROUND: The pH and voltage-regulated Slo3 K(+) channel, a homologue of the
      Ca(2+)- and voltage-regulated Slo1 K(+) channel, is thought to be primarily
      expressed in sperm, but the properties of Slo3 studied in heterologous systems
      differ somewhat from the native sperm KSper pH-regulated current. There is the
      possibility that critical partners that regulate Slo3 function remain
      unidentified. The extensive amino acid identity between Slo3 and Slo1 suggests
      that auxiliary beta subunits regulating Slo1 channels might coassemble with and
      modulate Slo3 channels. Four distinct beta subunits composing the KCNMB family
      are known to regulate the function and expression of Slo1 Channels.
      METHODOLOGY/PRINCIPAL FINDINGS: To examine the ability of the KCNMB family of
      auxiliary beta subunits to regulate Slo3 function, we co-expressed Slo3 and each
      beta subunit in heterologous expression systems and investigated the functional
      consequences by electrophysiological and biochemical analyses. The beta4 subunit
      produced an 8-10 fold enhancement of Slo3 current expression in Xenopus oocytes
      and a similar enhancement of Slo3 surface expression as monitored by YFP-tagged
      Slo3 or biotin labeled Slo3. Neither beta1, beta2, nor beta3 mimicked the ability
      of beta4 to increase surface expression, although biochemical tests suggested
      that all four beta subunits are competent to coassemble with Slo3. Fluorescence
      microscopy from beta4 KO mice, in which an eGFP tag replaced the deleted exon,
      revealed that beta4 gene promoter is active in spermatocytes. Furthermore,
      quantitative RT-PCR demonstrated that beta4 and Slo3 exhibit comparable mRNA
      abundance in both testes and sperm. CONCLUSIONS/SIGNIFICANCE: These results argue
      that, for native mouse Slo3 channels, the beta4 subunit must be considered as a
      potential interaction partner and, furthermore, that KCNMB subunits may have
      functions unrelated to regulation of the Slo1 alpha subunit.

PMID- 19578544
TI  - The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency
      virus-1 are critical to protein stability.
AB  - Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key
      role in initiating viral replication and is an important target for developing
      anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in
      the turn RT (Gln(269)-Arg(277)) abrogated viral replication, but the replication
      capacity and RT activity was discordant. In this study, we further investigated
      why alanine substitutions at these two sites would affect viral replication. We
      found that both RT activity and RT protein were almost undetectable in viral
      particles of these two mutants, although the Pr160(gag-pol) mutants were properly
      expressed, transported and incorporated. Using protease inhibition assay, we
      demonstrated a correlation between the degradation of the RT mutants and the
      activity of viral protease. Our native gel analysis indicated that the mutations
      at 271 and 274 amino acids might cause conformational changes, leading to the
      formation of higher order oligomers instead of dimers, resulting in increased
      protein instability and susceptibility to viral protease. Thus, residues 271 and
      274 are critical to RT stability and resistance to viral protease. The
      conservation of the two amino acid residues among different strains of HIV-1 lent
      further support to this conclusion. The knowledge gained here may prove useful in
      drug design.

PMID- 19578545
TI  - Mimicking mussel adhesion to improve interfacial properties in composites.
AB  - The macroscale properties of polymer-matrix composites depend immensely on the
      quality of the interaction between the reinforcement phase and the bulk polymer.
      This work presents a method to improve the interfacial adhesion between metal
      oxides and a polymer matrix by performing surface-initiated polymerization (SIP)
      by way of a biomimetic initiator. The initiator was modeled after 3,4-dihydroxy-L
      phenylalanine (dopa), an amino acid that is highly concentrated in mussel foot
      adhesive proteins. Mechanical pull out tests of NiTi and Ti-6Al-4V wires from
      poly (methyl methacrylate) (PMMA) were performed to directly test the interfacial
      adhesion. These tests demonstrated improvements in maximum interfacial shear
      stress of 116% for SIP-modified NiTi wires and 60% for SIP-modified Ti-6Al-4V
      wires over unmodified specimens. Polymer chain growth from the metal oxides was
      validated using x-ray photoemission spectroscopy (XPS), ellipsometry, scanning
      electron microscopy (SEM), and contact angle analysis.

PMID- 19578546
TI  - The National Food and Nutrient Analysis Program: A decade of progress.
AB  - The National Food and Nutrient Analysis Program (NFNAP) was designed to expand
      the quantity and improve the quality of data in the United States Department of
      Agriculture (USDA) food composition databases through the collection and analysis
      of nationally representative samples of foods and beverages. This paper describes
      some of the findings from the NFNAP and its impact on the food composition
      databases produced by USDA. The NFNAP employs statistically valid sampling plans,
      comprehensive quality control, and USDA analytical oversight as part of the
      program to generate new and updated analytical data for food components. USDA
      food consumption and composition data were used to target those foods that are
      major contributors of nutrients of public health significance to the U.S. diet
      (454 Key Foods). Foods were ranked using a scoring system, divided into
      quartiles, and reviewed to determine the impact of changes in their composition
      compared to historical values. Foods were purchased from several types of
      locations, such as retail outlets and fast food restaurants in different
      geographic areas as determined by the sampling plan, then composited and sent for
      analysis to commercial laboratories and cooperators, along with quality control
      materials. Comparisons were made to assess differences between new NFNAP means
      generated from original analytical data and historical means. Recently generated
      results for nationally representative food samples show marked changes compared
      to database values for selected nutrients from unknown or non-representative
      sampling. A number of changes were observed in many high consumption foods, e.g.
      the vitamin A value for cooked carrots decreased from 1,225 to 860 RAE/100g; the
      fat value for fast food French fried potatoes increased by 13% (14.08 to 17.06
      g/100g). Trans fatty acids in margarine have decreased as companies reformulate
      their products in response to the required addition of trans fatty acids content
      on the nutrition label. Values decreased from 19.7 g/100 in 2002 to 14.8 g/100 in
      2006 for 80%-fat stick margarines and to 4.52 g/100 g for 80%-fat tub margarines.
      These changes reflect improved strategies for sampling and analysis of
      representative food samples, which enhance the reliability of nutrient estimates
      for Key Foods and subsequent assessments of nutrient intake.

PMID- 19578547
TI  - A pox on the mind: Disjunction of attention and memory in the processing of
      physical disfigurement.
AB  - The unfavorable treatment of people with physical disfigurements is well
      documented, yet little is known about basic perceptual and cognitive responses to
      disfigurement. Here, we identify a specialized pattern of cognitive processing
      consistent with the hypothesis that disfigurements act as heuristic cues to
      contagious disease. Disfigurements are often invariant across time and difficult
      to conceal, and thus observers can detect the presence of such cues without
      necessarily remembering the particular individuals bearing these cues. Indeed,
      despite the fact that disfigured faces were especially likely to hold disease
      sensitive perceivers' attention (Study 1), disfigured individuals were often
      confused with one another and thus not well remembered later (Study 2), revealing
      a disjunction of the typical relationship between elevated attention and elevated
      memory. We discuss the implications of our results for stigmatization of people
      with and without physical abnormalities and suggest the possibility that
      cognitive mechanisms for processing social information may be functionally tuned
      to the variant nature of important cues.

PMID- 19578548
TI  - Niemann-Pick type C disease proteins: orphan transporters or membrane rheostats?
AB  - Niemann-Pick type C (NPC) disease is a panethnic lysosomal lipidosis, which
      results in severe cerebellar impairment and death, and is proposed to be a
      consequence of defective metabolite transport. Numerous models of this disorder
      have defined the phenotypic impact of misfunction of the NPC proteins, however,
      their mechanism of action and definition of substrate(s) remain vague and
      disputed. The proteins may be lipid chaperones, nonspecific transporters, orphan
      transporters or membrane-sensing regulators ('rheostats') of other transport
      reactions. These issues pertain to the nature or even existence of a toxic
      metabolite as causative to this disorder and thus ultimately to treatment of the
      disease. This review will present the issues that underpin NPC disease and
      current or future avenues of treatment.

PMID- 19578552
TI  - A serum- and feeder-free technique of culturing human corneal epithelial stem
      cells on amniotic membrane.
AB  - PURPOSE: To describe a simple technique of cultivating human corneal epithelial
      stem cells using an Epilife culture medium under serum- and feeder-free
      conditions. METHODS: Cadaveric donor limbal corneal epithelial cells were
      cultured on denuded amniotic membranes using an explant technique that was free
      of serum and feeder cells in the Epilife medium containing a growth supplement of
      defined composition. These cells were assessed by phase contrast microscope. The
      expressions of the proposed corneal epithelial stem cell markers (p63, ATP
      binding cassette member 2 (ABCG2), and cytokeratin 15 and 19) and differentiation
      markers (cytokeratin 3, 12, connexin 43, and p75) were analyzed using reverse
      transcription polymerase chain reaction (RT-PCR) and immunocytochemical staining.
      RESULTS: Successful cultures were obtained, resulting in a monolayer to double
      layer cell sheets with a cobblestone-like morphology. RT-PCR and
      immunocytochemistry disclosed an expression of both putative limbal stem cell
      (LSC) markers and differentiation-associated markers in the cultured cells. Most
      of the cultured corneal epithelial cells that were immunopositive for putative
      LSC markers were smaller, more uniform, and closer to the limbal explant than
      cells positively stained with differentiation-associated markers. CONCLUSIONS: A
      serum- and feeder-free culture system using Epilife medium may grow human corneal
      epithelial equivalents, minimizing the risk of contamination during culture. The
      technique may also be useful for the clinical application of limbal stem cell
      culture.

PMID- 19578553
TI  - Association of polymorphisms in APOE, p53, and p21 with primary open-angle
      glaucoma in Turkish patients.
AB  - PURPOSE: To investigate the association between Apolipoprotein E (APOE), tumor
      suppressor protein p53 (p53), and cyclin-dependent kinase inhibitor 1A (p21)
      genes and primary open-angle glaucoma (POAG) in a cohort of Turkish subjects.
      METHODS: Seventy-five POAG patients (49 women, 26 men) and 119 healthy subjects
      (67 women, 52 men) were genotyped with polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). Allele and genotype frequencies between
      healthy subjects and glaucoma patients were compared by the chi(2) test, and
      intraocular pressure (IOP), cup/disc ratio (C/D) and visual field indices (MD and
      PSD) were compared among different APOE, p53, and p21 genotypes in POAG group. A
      p value <0.05 was considered as statistically significant. RESULTS: The mean ages
      were 63.8+/-9.5 and 61.8+/-10.2 years in POAG and control groups, respectively
      (p=0.18). There were no significant differences in the distribution of APOE, p53,
      and p21 genotypes between the healthy subjects and POAG patients (p=0.38, p=0.12,
      and p=0.2, respectively). There were no significant differences in maximum IOP,
      MD, and PSD values among different groups of p53 and p21 genotypes (p>0.05). POAG
      subjects with the epsilon2epsilon3 genotype had a worse PSD value (median=2.2)
      than those with the epsilon3epsilon4 genotype (median=1.77; p=0.01) and POAG
      subjects with the epsilon3epsilon3 genotype had worse MD and PSD values (median= 
      7.4 and 3.4, respectively) than those with the epsilon3epsilon4 genotype (median=
      -4.1 and 1.77, respectively; p=0.034 and 0.028, respectively). CONCLUSIONS: Our
      study found no link between polymorphisms in APOE, p53, and p21 genes and POAG in
      Turkish patients, although a larger sample is required to elucidate the role of
      these polymorphisms in the pathogenesis and course of glaucoma.

PMID- 19578555
TI  - Purification and characterization of enterocin 62-6, a two-peptide bacteriocin
      produced by a vaginal strain of Enterococcus faecium: Potential significance in
      bacterial vaginosis.
AB  - A bacteriocin produced by a vaginal isolate of Enterococcus faecium strain 62-6,
      designated enterocin 62-6, was characterized following purification and DNA
      sequence analysis and compared to previously described bacteriocins. Enterocin 62
      6 was isolated from brain heart infusion (BHI) culture supernatants using
      ammonium sulfate precipitation followed by elution from a Sepharose cation
      exchange column using a continuous salt gradient (0.1-0.7 M NaCl). SDS-PAGE of an
      active column fraction resulted in an electrophoretically pure protein, which
      corresponded to the growth inhibition of the sensitive Lactobacillus indicator
      strain in the gel overlay assay. Purified enterocin 62-6 was shown to be heat-
      and pH-stable, and sensitive to the proteolytic enzymes alpha-chymotrypsin and
      pepsin. Results from mass spectrometry suggested that it comprised two peptides
      of 5206 and 5219+/-1 Da, which was confirmed by DNA sequence analysis. The
      characteristics of enterocin 62-6 as a small, heat- and pH-stable, cationic,
      hydrophobic, two-peptide, plasmid-borne bacteriocin, with an inhibitory spectrum
      against a broad range of Gram-positive but not Gram-negative bacteria, were
      consistent with its classification as a class IIc bacteriocin. Furthermore, its
      wide spectrum of growth inhibitory activity against Gram-positive bacteria of
      vaginal origin including lactobacilli, and stability under the acidic conditions
      of the vagina, are consistent with our hypothesis that it could have potential
      significance in disrupting the ecology of the vaginal tract and pave the way for
      the establishment of the abnormal microbiota associated with the vaginal syndrome
      bacterial vaginosis. This is the first class IIc bacteriocin produced by a strain
      of E. faecium of vaginal origin to be characterized.

PMID- 19578556
TI  - Stress and Binge Drinking: A Daily Process Examination of Stressor Pile-up and
      Socioeconomic Status in Affect Regulation.
AB  - The goal of this study was to enhance understanding of the interconnections
      between stress, negative mood, and alcohol use. To achieve this goal, daily diary
      data collected over eight consecutive nights from a nationally representative
      adult cohort were used to identify if: 1) both daily stress and stress pile-up
      were associated with increased risk of binge drinking, 2) negative affect
      mediated associations between stressor variables and binge drinking, and 3)
      associations among stress, negative affect and binge drinking were moderated by
      educational attainment as an indicator of socioeconomic status. Results from
      hierarchical linear models indicated that the odds of binge drinking was higher
      on days that individuals experienced more severe stressors in contrast to no
      stress days. Further, the odds of binge drinking also increased as stressors
      piled-up over consecutive days. There was no evidence indicating that negative
      affect mediated the effect of stressor exposure on binge drinking. Associations
      between stressor exposure (both daily stress and stress pile-up) and binge
      drinking were moderated by educational attainment. The findings of this study are
      consistent with previous daily process studies examining the association between
      stress and alcohol. However, the pattern of results from this study suggest that
      affect regulation researchers need to handle "stress" in a multidimensional way
      and better situate stressors and individuals stress responses within their social
      context.

PMID- 19578554
TI  - Expression of muscarinic receptors in human and mouse sclera and their role in
      the regulation of scleral fibroblasts proliferation.
AB  - PURPOSE: To determine the expression of muscarinic receptor subtypes (mAChRs) in
      human and mouse scleral fibroblasts (SFs), to investigate the mechanism that
      mediate the role mAChRs play in cell proliferation, and to explore the underlying
      intracellular signaling pathways involved in mouse SFs with treatment of
      muscarinic agents. METHODS: Reverse transcription polymerase chain reaction (RT
      PCR) was used to detect mRNA expression of mAChRs in the human and mouse sclera.
      Western blot analysis and immunocytochemistry were used to detect proteins of
      mAChRs in the cultured SFs. An immunohistochemical study was used to further
      detect the presence of mAChR proteins in frozen scleral sections. BrdU (5-bromo-2
      deoxyuridine ) cell proliferation assay was performed to measure DNA synthesis.
      Enzyme linked immunosorbent assay (ELISA) was used to measure in vitro kinase
      activity for epidermal growth factor receptor (EGF-R), fibroblast growth factor
      (FGF-2), transforming growth factor (TGF)-beta1, and extracellular signal
      regulated kinase (ERK)1/2. Expressions of epidermal growth factor-receptor (EGF
      R); protein kinase C (PKC); Proline-rich tyrosine kinase 2 (Pyk-2), v-raf murine
      sarcoma viral oncogene homolog B1 (B-Raf), Rat Sarcoma (Ras), c-Jun N-terminal
      kinases (JNK1/2), and ERK1/2 were detected by immunoblot. RESULTS: mAChR for
      subtypes M(1)-M(5) were detected in both mouse and human SFs by protein,
      cellular, and mRNA analysis. EGF-R, PKC, Pyk-2, B-Raf, Ras, JNK1/2, and ERK1/2
      were activated after treatment by agonists and antagonists, indicated by changes
      in phosphorylation of these proteins. Atropine abolished the carbachol-induced
      activation of SF cell proliferation in a concentration-dependent manner.
      Carbachol also activated p42/44 mitogen-activated protein kinase (MAPK) and Ras
      in a time-dependent manner. Muscarinic agents also modulated fibroblast growth
      factor expression in these cells. CONCLUSIONS: This study confirms the presence
      and functional role of all five mAChRs in human and mouse SFs. These results show
      that proliferative responses of SFs to muscarinic receptor stimulation are
      mediated via the activation of the classical MEK-ERK-MAPK cascade.

PMID- 19578557
TI  - QUANTITATIVE CELL MOTILITY FOR IN VITRO WOUND HEALING USING LEVEL SET-BASED
      ACTIVE CONTOUR TRACKING.
AB  - Quantifying the behavior of cells individually, and in clusters as part of a
      population, under a range of experimental conditions, is a challenging
      computational task with many biological applications. We propose a versatile
      algorithm for segmentation and tracking of multiple motile epithelial cells
      during wound healing using time-lapse video. The segmentation part of the
      proposed method relies on a level set-based active contour algorithm that
      robustly handles a large number of cells. The tracking part relies on a detection
      based multiple-object tracking method with delayed decision enabled by multi
      hypothesis testing. The combined method is robust to complex cell behavior
      including division and apoptosis, and to imaging artifacts such as illumination
      changes.

PMID- 19578558
TI  - Teacher-Student Support, Effortful Engagement, and Achievement: A 3-Year
      Longitudinal Study.
AB  - Measures of teacher-student relationship quality (TSRQ), effortful engagement,
      and achievement in reading and math were collected once each year for 3
      consecutive years, beginning when participants were in 1st grade, for a sample of
      671 (53.1% male) academically at-risk children attending 1 of 3 school districts
      in Texas. In separate latent variable structural equation models, the authors
      tested the hypothesized model, in which Year 2 effortful engagement mediated the
      association between Year 1 TSRQ and Year 3 reading and math skills. Conduct
      engagement was entered as a covariate in these analyses to disentangle the
      effects of effortful engagement and conduct engagement. Reciprocal effects of
      effortful engagement on TSRQ and of achievement on effortful engagement were also
      modeled. Results generally supported the hypothesized model. Year 1 variables had
      a direct effect on Year 3 variables, above year-to-year stability. Findings
      suggest that achievement, effortful engagement, and TSRQ form part of a dynamic
      system of influences in the early grades, such that intervening at any point in
      this nexus may alter children's school trajectories.

PMID- 19578559
TI  - A Sensemaking Approach to Ethics Training for Scientists: Preliminary Evidence of
      Training Effectiveness.
AB  - In recent years, we have seen a new concern with ethics training for research and
      development professionals. Although ethics training has become more common, the
      effectiveness of the training being provided is open to question. In the present
      effort, a new ethics training course was developed that stresses the importance
      of the strategies people apply to make sense of ethical problems. The
      effectiveness of this training was assessed in a sample of 59 doctoral students
      working in the biological and social sciences using a pre-post design with follow
      up, and a series of ethical decision-making measures serving as the outcome
      variable. Results showed that this training not only led to sizable gains in
      ethical decision-making, but that these gains were maintained over time. The
      implications of these findings for ethics training in the sciences are discussed.

PMID- 19578560
TI  - RACE, INCOME, AND ENVIRONMENTAL INEQUALITY IN THE UNITED STATES.
AB  - This article asks whether the relationship between neighborhood and household
      income levels and neighborhood hazard levels varies according to neighborhood and
      household racial composition. Using a national, census tract-level data set, the
      authors find that black, white, and Hispanic households with similar incomes live
      in neighborhoods of dissimilar environmental quality, that the association
      between neighborhood and household income levels and neighborhood hazard levels
      varies according to neighborhood and household racial composition, and that
      increases in neighborhood and household income levels are more strongly
      associated with declining hazard levels in black neighborhoods and households
      than in white neighborhoods and households. These findings contradict Wilson's
      claim that the significance of race has declined in the modern industrial period
      and demonstrate that environmental racial inequality is not the product of racial
      income inequality. In addition, these findings suggest that the impact of higher
      incomes on black/white proximity to environmental hazards has less to do with
      increases in white geographic mobility (relative to black geographic mobility)
      than with the ability of higher income blacks to escape the highly polluted,
      disorganized, and deteriorated neighborhoods to which so many low-income blacks
      are confined.

PMID- 19578561
TI  - Quality Child Care Supports the Achievement of Low-Income Children: Direct and
      Indirect Pathways Through Caregiving and the Home Environment.
AB  - Existing studies of child care have not been able to determine whether higher
      quality child care protects children from the effects of poverty, whether poverty
      and lower quality child care operate as dual risk factors, or whether both are
      true. The objective of the current study was to test two pathways through which
      child care may serve as a naturally occurring intervention for low-income
      children: a direct pathway through child care quality to child outcomes, and an
      indirect pathway through improvements in the home environment. Children were
      observed in their homes and child care settings at 6, 15, 24, and 36 months. An
      interaction between family income-to-needs ratio and child care quality predicted
      School Readiness, Receptive Language, and Expressive Language, as well as
      improvements in the home environment. Children from low-income families profited
      from observed learning supports in the form of sensitive care and stimulation of
      cognitive development, and their parents profited from unobserved informal and
      formal parent supports. Policy implications are discussed.

PMID- 19578562
TI  - Up Versus Down: The Role of Intersensory Redundancy in the Development of
      Infants' Sensitivity to the Orientation of Moving Objects.
AB  - According to the intersensory redundancy hypothesis (IRH), during early
      development, perception of nonredundantly specified properties is facilitated in
      unimodal stimulation as compared with bimodal stimulation. Later in development,
      attention becomes more flexible and infants can detect nonredundantly specified
      properties in both unimodal and bimodal stimulation. This study tested these
      predictions by assessing the development of infants' sensitivity to the
      orientation of an object striking a surface, information that is nonredundantly
      specified in visual and in audiovisual stimulation. Infants of 3, 5, and 8 months
      were habituated to unimodal visual or bimodal, synchronous, audiovisual films of
      a hammer tapping a rhythm in 1 of 2 orientations (upward vs. downward). Results
      demonstrated an Age * Condition interaction, where younger infants (3 and 5
      months) detected the orientation change in unimodal but not bimodal stimulation,
      whereas older infants (8 months) detected the change in both types of
      stimulation. Further, in a control study, 3-month-olds detected the orientation
      change when bimodal stimulation was asynchronous, demonstrating that temporal
      synchrony impaired performance in the bimodal condition. These findings converge
      with those of prior studies and support predictions of the IRH.

PMID- 19578563
TI  - DIFFERENT STROKES FOR DIFFERENT GANGS? AN ANALYSIS OF CAPITAL AMONG LATINO AND
      ASIAN GANG MEMBERS.
AB  - Gang activity and membership were noted to be significantly related to financial
      rewards. As such, gang membership and gang activity should also be understood
      from an economic perspective. In this article, Pierre Bourdieu's framework of
      capital is used to analyze two separate samples of Latino and Asian gang members.
      Stark contrasts in socioeconomic backgrounds are recorded among the two samples
      of gang members, and gang membership and activities are also noticeably
      dissimilar. Accessibility to economic, cultural, and social capital is argued to
      affect gang membership and activities. The results suggest that the availability
      of legitimate and illegitimate capital greatly affects the trajectory and the
      length of gang involvement. Also, gangs provide significant material and social
      capital for the respondents of the study.

PMID- 19578564
TI  - The strategic role of Fiocruz in the context of Brazil's National Policy for
      Science, Technology, and Innovation in Health.

PMID- 19578565
TI  - [Interventions to solve overcrowding in hospital emergency services: a systematic
      review].
AB  - This review discusses interventions aimed at solving the problem of overcrowding
      in hospital emergency services (HES), characteristic of low organizational
      effectiveness. In free-access and restricted-access databases, the target
      descriptors were 'overcrowding; emergency; medicine; first aid'. The survey
      identified 66 citations of interventions, grouped in 47 related interventions.
      The majority of the studies used observational designs that evaluated the results
      before and after interventions. Of the 47 related interventions, 34 had results
      for organizational performance. Four were the most frequently cited:
      implementation of an observation unit for patients already hospitalized and
      awaiting diagnosis or clinical stabilization; designation of a dedicated nursing
      station for the patient's admission, discharge, or transfer; establishment of
      protocols with indicators of operational saturation and implementation of an
      emergency care unit. Analyzing 21 interventions that were intended to solve
      overcrowding in HES and with positive results for length-of-stay, 15 were related
      to patient stream improvement, interfering actively and positively in patient
      stream. Interventions that increased access barriers or that merely improved the
      HES structure were ineffective.

PMID- 19578566
TI  - [Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): cross
      cultural adaptation for use in Brazil].
AB  - This article presents the results of the translation and cross-cultural
      adaptation of the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE) and the test-retest reliability of a version to be used in Brazil. An
      instrument review committee analyzed the conceptual and item equivalence. In
      order to analyze semantic equivalences, three translations and three back
      translations were performed; a summary version was devised and pre-tested, and a
      test version elaborated. The Cronbach's +/- coefficient and intraclass
      correlation coefficient (ICC) were used to measure the internal consistency and
      test-retest reliability, respectively. Of the 169 informants assessed, 97 were
      retested. A Cronbach's +/- of 0.94 and an ICC of 0.92 were found. The reliability
      levels lead to the conclusion that the IQCODE-BR version is easy to comprehend.
      Satisfactory equivalence to the original version was observed.

PMID- 19578567
TI  - Factors associated with stages of change for red meat and vegetable intake by
      Japanese-Brazilians.
AB  - Stages of change assess individual motivation for lifestyle changes, contributing
      to the development of more effective intervention strategies. The objective of
      the present study was to identify factors associated with stages of change for
      lower intake of red meat and higher intake of vegetables in a cross-sectional
      analysis of 578 Japanese-Brazilians aged 30-90 years. In adjusted logistic
      regression models, the odds ratios for women (OR = 1.89; 95%CI: 1.154; 3.103) and
      physically active individuals (OR = 1.00; 95%CI: 1.000; 1.001) were positively
      associated with stage of 'action' for the higher intake of vegetables. Inverse
      associations were observed between central obesity (OR = 0.5; 95%CI: 0.351;
      0.887) and highest tertile of red meat intake (OR = 0.50; 95%CI: 0.302; 0.817),
      as well as a positive association between age (OR = 1.04; 95%CI: 1.020; 1.070)
      and the stage of 'action' to the lower intake of meat were verified. Motivation
      for Japanese-Brazilians to change their food intake was linked to lifestyle.
      Stage of change is an important factor in mediating food intake behavior change.

PMID- 19578568
TI  - [Compression of mortality: a study on the variability of age at death in the
      State of Sao Paulo, Brazil, 1980-2005].
AB  - In the present study, changes in the population mortality structure in the State
      of Sao Paulo, Brazil, were analyzed from 1980 to 2005, aimed at identifying the
      effects of these changes on the variability of age at death. Evidence of a change
      in the distribution of deaths toward more advanced ages was found, and the mean
      lifespan for the overall population increased by seven years during the period.
      Two different scenarios were observed. The first (1980-1995) showed an increase
      in the variability of age at death. The second (1995-2005) showed a downward
      trend in variability. Estimates beyond a given quartile of the death distribution
      by age indicated that compression of mortality took place throughout the entire
      period. However, variability of age at death was lower for males as compared to
      females.

PMID- 19578569
TI  - [Malaria and hematological aspects among residents to be impacted by reservoirs
      for the Santo Antonio and Jirau Hydroelectric Power Stations, Rondonia State,
      Brazil].
AB  - In Rondonia State, Brazil, two new hydroelectric plants, Santo Antonio and Jirau,
      are scheduled for construction on the Madeira River, upriver from the State
      capital, Porto Velho. The current study analyzes malaria prevalence before the
      construction and provides information on the possible impacts of malaria burden
      related to the influx of thousands of persons attracted by direct and indirect
      employment opportunities. According to the findings, malaria is present
      throughout the region, with varying prevalence rates. The existence of potential
      asymptomatic malaria carriers among the local population may be epidemiologically
      relevant and should be considered in the malaria control programs organized by
      public authorities and companies responsible for building the power plants, aimed
      at early diagnosis and treatment, vector control, water supply, and
      infrastructure in the urban areas.

PMID- 19578570
TI  - [Exploring breast cancer risk factors in Kaingang women in the Faxinal Indigenous
      Territory, Parana State, Brazil, 2008].
AB  - This study analyzes the health of Kaingang women in the Faxinal indigenous
      territory in Parana State, Brazil, with regard to risk factors for breast cancer.
      A descriptive and exploratory investigation was undertaken that included 95.4% of
      females 20 years or over. Data showed that 92.3% of Kaingang women reported
      breastfeeding for more than one year; 41.4% had more than 5 children; mean age at
      menarche was 13.4 years; 61.5% had never heard of breast cancer; breast self
      examination was only performed by 2.9%; 81.7% reported no clinical breast
      examination by a physician; 99% had never had a mammogram. No cases of breast or
      non-breast cancer were reported. The study highlights protective factors against
      carcinogenesis and the absence of key risk factors like hormone replacement
      therapy for more than five years and alcohol consumption in most Kaingang women.

PMID- 19578571
TI  - [Utilization of fully Bayesian modeling to detect patterns in relative risk
      variation for infant mortality in Rio Grande do Sul State, Brazil].
AB  - The infant mortality rate is one of the key indicators used to measure a
      population's quality of life. The State of Rio Grande do Sul has a social and
      economic indicator called the Socioeconomic Development Index (IDESE). Most
      studies analyze the infant mortality rate in relation to risk factors, visually
      aided by maps. This study presents the methodology and an application of a
      Spatial Epidemiology method called the ecological correlation, using hierarchical
      Bayesian procedures. The article discusses the main problems found in ecological
      correlations, such as spatial autocorrelation and the estimator's instability for
      small areas. To overcome these difficulties, the relative risk estimate obtained
      by spatial regression analysis using fully Bayesian estimation is presented. The
      infant mortality rate is analyzed in all 496 municipalities of Rio Grande do Sul
      for the years 2001 to 2004. Several models with spatial component and different
      variables from the IDESE/2003 were compared. The model using spatial structure
      along with the variable 'education' was considered the best choice. With this
      methodology, it was possible to obtain a more interpretable pattern of infant
      mortality risk in Rio Grande do Sul.

PMID- 19578572
TI  - [Knowledge on risk factors for chronic diseases: a population-based study].
AB  - The aim of the present study was to evaluate public awareness of the association
      between four behavioral factors (sedentary lifestyle, smoking, alcohol abuse, and
      inadequate diet) and eight diseases (diabetes, hypertension, AIDS, osteoporosis,
      lung cancer, depression, liver cirrhosis, and acute myocardial infarction). We
      conducted a population-based cross-sectional study including 2,096 individuals 10
      years or older. A random clustered sampling strategy was used. For each
      behavioral factor, a knowledge score was constructed, ranging from zero to eight
      points. The highest mean score was observed for inadequate diet (5.3), followed
      by smoking (5.1), sedentary lifestyle (4.7), and alcohol abuse (4.5). Overall,
      higher knowledge scores were observed among people with high socioeconomic status
      and more schooling, and in intermediate age groups. Government health promotion
      strategies are needed to raise public awareness of risk factors for chronic
      diseases.

PMID- 19578573
TI  - [Contributions by Conversation Analysis to healthcare studies: reflections based
      on patients' attributions].
AB  - This study is part of a larger research project aimed at investigating physician
      patient interactions in women's health. In this article, by looking at
      naturalistic data, which consists of 144 fully transcribed audio recordings of
      face-to-face interactions between gynecologists/obstetricians and female
      patients, we propose to: (1) present the theoretical and methodological approach
      of Conversation Analysis to health studies in Brazil; (2) discuss how
      Conversation Analysis can reveal how 'macro' questions (e.g. National Policy for
      the Humanization of Healthcare) are (or are not) translated into interactional
      practices at the 'micro' level and, thus, emphasize the issues of language and
      communication, only briefly discussed in the HumanizaSUS documents; and (3)
      analyze how a specific interactional phenomenon, 'attribution' (i.e. voluntary
      explanations about the possible causes of their problems), might describe
      ordinary and concrete humanization practices in healthcare services.

PMID- 19578574
TI  - Vulnerability and self-perceived health status among light and heavy smokers: the
      relationship to short-term fear appeal tobacco control messages.
AB  - It is important to stimulate smokers to acquire some level of risk perception
      associated with their current behavior in order to motivate smoking cessation.
      The present article attempts to understand how the content of short-term fear
      appeal government tobacco messages may interact with different levels of daily
      cigarette consumption in order to affect smokers' vulnerabilities, expressed by
      self-perceived health status. A Poisson model was used to estimate the prevalence
      ratio of fair or poor self-perceived health status (FPHS) according to daily
      cigarette consumption. We also calculated the proportions of smokers who stated
      that selected health warning pictures on cigarette packets encourage people to
      quit smoking, stratified by self-perceived health status and daily cigarette
      consumption. The proportion of smokers with FPHS was 25% higher among those who
      smoked > 20 cigarettes/day (p = 0.01). Among smokers with FPHS, heavy smokers
      showed the highest proportions of responses in favor of selected warning pictures
      most closely related to losses in ordinary daily living, such as shortness of
      breath and being bothered by cigarette addiction. Short-term loss-framed tobacco
      control messages seem to have raised awareness of vulnerability among heavier
      smokers.

PMID- 19578575
TI  - Factors associated with the incidence of urban visceral leishmaniasis: an
      ecological study in Teresina, Piaui State, Brazil.
AB  - The objective of this study was to identify socioeconomic and environmental
      factors associated with the incidence of visceral leishmaniasis in the city of
      Teresina, Piaui State, Brazil. This was an ecological study based on 1,744 cases
      reported from 1991 to 2000, and the city's neighborhoods served as the unit of
      analysis. Mean annual incidence rates were related to socioeconomic and
      demographic indicators and a vegetation index derived from remote sensing images
      by means of spatial multiple linear regression models. The neighborhoods with the
      highest incidence rates were mostly located in the city's peripheral areas.
      Multivariate analysis identified an interaction between population growth and the
      vegetation index, so that areas with high population growth and abundant
      vegetation showed the highest incidence rates. The percentage of households with
      piped water was inversely associated with visceral leishmaniasis incidence.
      Spatial distribution of visceral leishmaniasis in Teresina during the 1990s was
      heterogeneous, and incidence of the disease was associated with the peripheral
      neighborhoods with the heaviest vegetation cover, subject to rapid occupation and
      lack of adequate sanitation infrastructure.

PMID- 19578576
TI  - [Linkage between live birth and infant death records in a municipality in
      Northeast Brazil: quality of the information system].
AB  - The objective was to analyze the quality of the information systems for live
      births (SINASC) and mortality (SIM) based on database linkages. SINASC contained
      11,182 certificates of live birth (CLB) from Jan. 1, 2000, to Dec. 31, 2002, and
      the SIM database recorded 233 death certificates (DC) for infants (< one year of
      age) from Jan. 1, 2000, to Dec. 31, 2003, 207 infant death investigations from
      Jan. 1, 2000, to Dec. 31, 2004, and 17 CLB attached to infant death
      investigations. Each DC was matched with a CLB through manual review. Of the
      11,182 births in SINASC, 69 duplicate CLB and 3 CLB without the mother's name
      were eliminated. The 211 SIM/infant death investigations showed the following: 25
      CLB (35.2% of deaths), 33 CLB (55.9% of deaths), 57 CLB (75% of deaths), and 4
      CLB (80% of deaths). For 92 DC (43.6% of 211 deaths), matching was not possible,
      since there was no CLB. Infant death investigations were an important
      complementary source of 53 DC and 17 CLB. The study contributed to evaluation of
      the data quality and identification of flaws, favoring the reliability of birth
      and infant death records.

PMID- 19578577
TI  - [Prevalence of burnout syndrome in nursing staff in a large hospital in south of
      Brazil].
AB  - Burnout syndrome is a chronic adaptive disorder that affects workers and is
      characterized by three forms of psychological distress: emotional exhaustion,
      depersonalization, and a sense of low personal fulfillment. A cross-sectional
      quantitative design was used to apply questionnaires including socio-cultural
      data and the Maslach Burnout Inventory in 151 nurses and nurse technicians,
      representing 54.1% of this professional category in a large general hospital in
      Tubarao, Santa Catarina State, Brazil. Mean scores were: emotional exhaustion
      (17), depersonalization (7.79), and low personal fulfillment (36.6). According to
      the criterion proposed by Ramirez et al., no cases of burnout were diagnosed.
      According to the criteria by Grunfeld et al., 35.7% of the interviewees displayed
      burnout. The standard profile of workers with burnout identified in the study
      was: nurse technicians, female gender, age 26-35 years, married, with no
      children, and with five or more years in the profession. Hospital wards or areas
      with the highest proportion of nursing staff with burnout were the grouped
      hospital sectors (42.6%), ICU (25.9%), and neonatal ICU (18.5%). There was no
      statistically significant association between ward or hospital area and burnout.

PMID- 19578578
TI  - [Obesity prevalence and associated factors in the elderly in Pelotas, Rio Grande
      do Sul State, Brazil: obesity classification according to two cutoff points for
      body mass index].
AB  - The aim of this study was to estimate obesity prevalence and associated factors
      in the elderly, according to two cutoff points for body mass index (BMI). This
      was a cross-sectional, population-based study of a sample of 596 elderly
      residents in Pelotas, southern Brazil. Nutritional status was evaluated through
      BMI based on self-reported weight and stature. Poisson multiple regression with
      hierarchical analysis was applied, with two dependent variables for definition of
      obesity: BMI > 27 kg/m(2) and BMI > or =30 kg/m(2), the cutoff points proposed by
      Lipschitz and the World Health Organization, respectively. Prevalence of obesity
      was 48.7% (95%CI: 44.6-52.7) for BMI > 27 kg/m2 and 25.3% (95%CI: 21.9-29.0) for
      BMI > or =30 kg/m(2). Two multiple regression models showed an association
      between obesity and female gender and age. BMI > 27 kg/m(2) showed an association
      with age and smoking and BMI > or =30 kg/m(2) with sedentary lifestyle. Obesity
      prevalence was high in this group of elderly. For the Brazilian elderly
      population and from a public health perspective, the study suggests the use of a
      more sensitive cutoff point, namely BMI > 27 kg/m(2).

PMID- 19578579
TI  - [A population-based study on cost-related underuse of medicines by the elderly in
      Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil].
AB  - The aim of this study was to estimate the prevalence of cost-related underuse of
      medicines and associated factors in a representative sample of 1,134 elderly
      individuals in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil.
      Prevalence of cost-related underuse was 12.9%. After adjustments in the
      multivariate model, cost-related underuse was higher in individuals with income
      less than twice the minimum wage (PR = 0.57; 95%CI: 0.34-0.97), without health
      plan coverage (PR = 0.68; CI95%: 0.46-0.99), with low frequencies of physician
      patient dialogue concerning health/treatment (rarely/never, PR = 1.79; 95%CI:
      1.10-2.90), with fair to poor self-rated health (PR = 1.66; 95%CI: 0.95-2.90 and
      PR = 2.49; 95%CI: 1.38-4.48, respectively), and with multiple comorbidities (one,
      PR = 2.51; 95%CI: 0.99-6.35; two, PR = 3.51; 95%CI: 1.40-8.72 and three or more,
      PR = 4.52; 95%CI: 1.79-11.41). Our results suggest adherence problems within this
      population due to a communication gap between seniors and physicians on treatment
      related aspects and to the lack of health plan coverage. Especially worrisome is
      the high risk of cost-related underuse among elderly with poor health.

PMID- 19578580
TI  - [Aspects related to choice of type of delivery: a comparative study of two
      maternity hospitals in Sao Luis, State of Maranhao, Brazil].
AB  - This study aimed to analyze aspects related to choice of type of delivery in two
      maternity hospitals, one public and the other private, in Sao Luis, Maranhao
      State, Brazil. This cross-sectional study compared 163 primiparous women in a
      public maternity hospital and 89 in a private hospital, with mean ages of 21.63
      +/- 5.24 and 28.8 +/- 5.41 years, respectively. In the public hospital, 79.1% of
      the women reported preferring vaginal deliveries, while in the private hospital
      67.4% of the women preferred cesareans (p < 0.0001). Cesareans were performed in
      46% of the women in the public maternity hospital and 97.8% of those in the
      private hospital (p < 0.0001). Patient satisfaction was high for both modes of
      delivery, but the desire to repeat the same mode was reported more frequently by
      women with vaginal deliveries (71.6% vs. 41.3% in the public maternity hospital
      and 100% vs. 65.5% in the private). In the public maternity hospital, the
      cesarean subgroup included more white and higher-income women. The cesarean rate
      was thus high in both maternity hospitals and was significantly higher in the
      private hospital; the study also showed a preference for vaginal delivery in the
      public hospital and cesareans in the private.

PMID- 19578581
TI  - User satisfaction with pharmacy services in the Brazilian National STD/AIDS
      Program: validity and reliability issues.
AB  - The objective of this study is to evaluate the psychometric properties of a user
      satisfaction scale regarding the Brazilian National STD/AIDS Program,
      specifically related to dispensing AIDS medicines. The scale was developed and
      applied in a study covering 10 Brazilian States that evaluated the quality of
      medicine dispensing. The questionnaire was answered by 1,412 people living with
      HIV and undergoing antiretroviral therapy. Construct validation involved two
      stages of factor analysis. The item-total correlation matrix was analyzed, and
      tests for associations between the target variable, socio-demographic variables,
      and related constructs were performed. Reliability was studied by means of the
      sub-scales' internal consistency, estimated by Cronbach's alpha. Five relevant
      satisfaction dimensions were identified. A moderate level of internal consistency
      was found for these dimensions, suggesting they were adequate. The results of the
      association tests agreed with other studies reported in the literature. We
      conclude that the instrument is appropriate for application in similar
      populations with adequate psychometric characteristics and serves to measure
      users' assessments of the pharmaceutical services received and helps to orient
      improvements in such services.

PMID- 19578582
TI  - [Forum: twenty years of experience and the challenge with the Unified National
      Health System. Introduction].
AB  - This Introduction presents the Forum on the 20 years of experience with the
      Unified National Health System (SUS), consisting of 3 articles and a postscript.
      The first article provides a historical overview of the implementation of the
      SUS, in light of the Constitutional provisions pertaining to health. It discusses
      the context and main issues underlying the creation of the SUS in Brazil and
      proposes a renewed linkage between health sector policies and an expanded project
      for Brazilian society. The second article analyzes the SUS' dynamics; strides in
      access to and comprehensiveness of care; and challenges for the achievement of
      its objectives, in light of factors that are external to the system, involving
      the need for greater politicization of analyses on the issue. The third article
      approaches social and political processes that developed from 1988 to 2008. It
      mainly analyzes the history of two collegiate bodies under the SUS at the Federal
      level: the National Health Council and the Tripartite Inter-Managers' Commission.
      Despite the complexity identified by the authors and the important obstacles they
      identify, the reflections indicate that the SUS has been a successful social
      policy, besides contributing to the consolidation of democracy in Brazil.

PMID- 19578583
TI  - [Reflections on Brazilian National Health Reform after 20 years of experience
      with the Unified National Health System].
AB  - This article provides some reflections on the challenges that have arisen during
      20 of experience with the implementation of Brazil's Unified National Health
      System and the significance of Constitutional provisions related to health for
      both academic research and health sector managers. The article discusses the main
      issues during these 20 years and how they are currently managed, and concludes by
      inquiring into the need for reconnecting health sector projects to a broader
      project for Brazilian society, without which the original proposals for health
      run the risk of becoming merely managerial ones.

PMID- 19578584
TI  - [The Unified National Health System, 20 years: assessment and perspectives].
AB  - This article reviews the strides and challenges of the Brazilian Unified National
      Health System (SUS), based on an assessment of the results achieved and the
      constraints for effective consolidation of it objectives. The article focuses on
      three issues: the process of implementing the SUS, highlighting the institutional
      and political constraints, some of which as effects of previous policies; strides
      towards more accessible and comprehensive care, with an impact on some health
      indicators, and institutional innovations with positive impacts on the system's
      management; and challenges for consolidating the objectives, as a result of
      exogenous factors in relation to the SUS, emphasizing the need for its
      politicization and greater legitimization.

PMID- 19578585
TI  - [The Unified National Health System: decision-making forums and the political
      arena in health].
AB  - This article analyzes the creation of new political arenas in the Brazilian
      health sector as well as shifts in power relations among state and social
      political actors in the context of public health system reform, focusing on the
      last two decades. The three main conclusions are the following: The creation of
      forums in which government actors can establish agreements that allow the shared
      national, State, and municipal coordination of management measures have
      strengthened the positions of these actors in the health political arena. Social
      actors, led by representatives of professional health societies, were both urged
      (and also took the initiative) to submit their demands and proposals through
      participatory forums that dealt mainly with secondary political issues, thus
      steadily losing the capacity to influence the real decision-making process in the
      sector. Market stakeholders took little part in the participatory forums, rather
      preferring to exert their influence directly on public decision-makers and to
      implement adaptive strategies to increase their profits.

PMID- 19578586
TI  - [Forum: twenty years of experience and the challenge with the Unified National
      Health System. Postscript].

PMID- 19578587
TI  - [Evaluation of the Brazilian National Dengue Control Plan].
AB  - This study aimed to describe and evaluate dengue patterns after the
      implementation of the National Dengue Control Plan (PNCD). Incidence rates were
      analyzed and correlated with previous rates and climatic, demographic, and
      socioeconomic variables for the Brazilian municipalities that were targeted for
      priority dengue control. We conducted descriptive studies of epidemiological
      indicators after the implementation of the national plan and a statistical
      analysis considering the incidence rates from the previous period and climatic,
      demographic, and socioeconomic variables, using multiple linear regression. We
      found a significant association between dengue incidence during the period
      following implementation of the PNCD (2003-2006) as compared to pre
      implementation (2001-2002), after adjusting for geographic and climatic
      indicators. Our findings suggest that the plan's objectives were not fully
      achieved. In conclusion, the persistent occurrence of dengue epidemics requires
      changes and reevaluation of current strategies, along with improvements in the
      dengue surveillance system.

PMID- 19578588
TI  - Dissemination of information on visceral leishmaniasis from schoolchildren to
      their families: a sustainable model for controlling the disease.
AB  - A model for the dissemination of information on visceral leishmaniasis from
      schoolchildren to their families was evaluated in two schools in Caete, Minas
      Gerais State, Brazil. Age ranged from 9 to 17 years in the two schools, one
      receiving the intervention (with 92 students) and the other serving as the
      control (96 students). All the students attended a class and received a pamphlet
      on visceral leishmaniasis. The intervention consisted of a homework assignment in
      which the student discussed the class content and pamphlet with a family member.
      Knowledge by family members (n = 100) on visceral leishmaniasis was evaluated
      with a pre and post-intervention questionnaire applied by a health agent, who
      also completed a form on hygiene around the household as observed during the home
      visit. A significant improvement was observed in knowledge and hygiene (e.g.,
      sweeping of leaves, fruit, and branches from the yards) among the families that
      were exposed to the intervention (p < 0.05). The spread of information on
      visceral leishmaniasis by schoolchildren can contribute to measures for
      preventing the disease.

PMID- 19578589
TI  - High-dose radioiodine outpatient therapy.

PMID- 19578590
TI  - [Markers of endothelial function in hypothyroidism].
AB  - The role of the endothelium in human disease has become the focus of scientific
      investigation and recently noninvasive and less expensive measures of endothelial
      function have become available. The endothelium modulates the vascular tonus and
      participates in inflammatory processes, platelet aggregation and thrombosis.
      Consequently, endothelial dysfunction has been implicated as an important event
      in the pathogenesis of atherosclerosis. Hypothyroidism is associated with an
      increased cardiovascular risk, and the assessment of endothelial function holds a
      great deal of promise as an assessment tool for the detection of preclinical
      cardiovascular alterations associated with thyroid dysfunction. Some recent
      studies have demonstrated a relationship between thyroid status and endothelial
      function, but large multicenter, placebo-controlled prospective trials are
      necessary to address this issue and the effect of levothyroxine replacement
      treatment in endothelial function. The objective of this work is to discuss the
      perspective picture in endothelium and thyroid function relationship.

PMID- 19578591
TI  - [Body mass regulation by estrogen and physical activity].
AB  - Female steroid hormones deficiency leads to a significant increase in body mass,
      but the possible central and peripheral mechanisms involved in increased food
      ingestion and fat accumulation in this situation are still unknown. In animal
      models, the specific lack of estrogen or its action produce progressive body mass
      gain, clearly demonstrating the possible role of this hormone in overweight after
      menopause. Obesity and overweight correspond to a relevant human health problem
      that can lead to premature death. Therefore unraveling the mechanisms underlying
      body mass gain is of great relevance, as well as the development of strategies to
      prevent its establishment. Energy balance regulation is associated with the
      control of body mass, and physical exercise is an important modulator of this
      homeostatic parameter. However, the influence of physical exercise in mass gain
      development during estrogen deficiency is controversial and depends on the
      exercise protocol used. In this study, we intend to review the data on the
      effects of estrogen deficiency on body mass gain in humans and animal models.

PMID- 19578592
TI  - [Radioiodine therapy of differentiated thyroid cancer: radiologic impact of out
      patient treatment with 100 to 150 mCi Iodine-131 activities].
AB  - PURPOSE: To evaluate exposure and dosimetry to family members and environment due
      to outpatient radioiodine therapy of differentiated thyroid carcinoma. METHODS:
      Twenty patients were treated with 100-150mCi of iodine-131 on an out-patient
      basis. Family members dosimetry (n = 27) and potential doses inside the house
      were measured with thermoluminescent dosimeters. Surface contamination and
      radioactive wastes were also monitored. RESULTS: Less than 1.0 mSv doses were
      found in 26 co-habitants and 2.8 mSv in a single case (inferior to the acceptable
      value of 5.0 mSv/procedure). Potential doses in the houses were inferior to 0.25
      mSv, excluding the patients bedroom (mean value = 0.69 mSv). Surface
      contamination (mean = 4.2 Bq.cm-2) were below clearance levels. Radioactive
      wastes generated had a volume of 2.5 liters and a total activity estimated in 90
      microCi, with a calculated exposure close to the background radiation levels.
      CONCLUSIONS: No radiological impact was detected after iodine therapy with 100
      150 mCi on an out-patient basis followed by experienced professionals.

PMID- 19578593
TI  - Analysis of glucose-dependent insulinotropic peptide receptor (GIPR) and
      luteinizing hormone receptor (LHCGR) expression in human adrenocortical
      hyperplasia.
AB  - OBJECTIVE: To analyze the aberrant expression of the GIPR and LHCGR in different
      forms of adrenocortical hyperplasia: ACTH-independent macronodular adrenal
      hyperplasia (AIMAH), primary pigmented nodular adrenocortical disease (PPNAD) and
      diffuse adrenal hyperplasia secondary to Cushing's disease (DAHCD). METHODS: We
      quantified GIPR and LHCGR expressions using real time PCR in 20 patients with
      adrenocortical hyperplasia (seven with AIMAH, five with PPNAD, and eight with
      DAHCD). Normal adrenals tissues were used as control and the relative expression
      was compared with beta-actin. RESULTS: GIPR and LHCGR expressions were
      demonstrated in all tissues studied. Median GIPR and LHCGR mRNA levels were 1.6;
      0.4; 0.5 and 1.3; 0.9; 1.0 in adrenocortical tissues from AIMAH, PPNAD and DAHCD
      respectively. There were no differences between GIPR and LHCGR expressions in all
      tissues studied. CONCLUSIONS: GIPR and LHCGR overexpression were not identified
      in the studied cases, thus suggesting that this molecular mechanism is not
      involved in adrenocortical hyperplasia in our patients.

PMID- 19578594
TI  - [Factors associated with insulin resistence in rural populations].
AB  - This study explores the relations of anthropometric, body composition
      assessments, biochemical and hemodynamic parameters with insulin resistance in
      two rural communities. Sample was composed by adults aged 18 or older, both
      sexes. Participants were excluded if pregnant and diabetic. Data collection
      included demographic lifestyle, hemodynamic, anthropometric and biochemical
      variables. From the 567 subjects, 50.4% were men and 49.6%, women. Most of the
      sample was non-white (75.7%), lived with partner (69.3%) and had low educational
      level. Overweight and obesity prevalences were 17.4% and 5.5%, respectively.
      Multivariate analysis found risk factors associated to insulin resistance for non
      diabetic adults with low income and educational level: overweight, obesity,
      elevated waist-to-hip ratio, C-reactive protein and skin color.

PMID- 19578595
TI  - Impact of abdominal fat and insulin resistance on arterial hypertension in non
      obese women.
AB  - OBJECTIVE: To evaluate the impact of abdominal fat and insulin resistance on
      arterial hypertension of non-obese women. METHODS: Thirty-five non-obese women
      (NO), age 35-68 years were studied, and divided into two groups according to the
      presence of hypertension (BP >or= 140 x 90 mmHg) (HT = hypertensive; NT =
      normotensive). Leptin measurement and oral glucose tolerance test (OGTT) to
      assess insulin were performed in these patients. A CT-scan was used to evaluate
      visceral (VF) and subcutaneous abdominal fat (SCF). The Central fat distribution
      index (CDI) was proposed to evaluate the impact of subcutaneous abdominal fat on
      central fat distribution in hypertensive patients. RESULTS: When compared to NT
      NO (n = 17) group, HT-NO (n = 18) showed higher blood pressure levels (systolic
      and diastolic), greater VF area (84.40 +/- 55.70 versus 37.50 +/- 23.00 cm(2); p
      = 0.036), greater SCF area (174.30 +/- 83.00 versus 79.80 +/- 27.40 cm(2); p =
      0.030), higher HOMAr index (1.59 +/- 0.72 versus 0.93 +/- 0.48 mmol*mU/L(2); p =
      0.006), higher CDI index (12.67 +/- 7.04 versus 6.19 +/- 2.57 cm(2)/kg) and
      higher leptin level (19.1 +/- 9.6 versus 7.4 +/- 3.5 ng/mL; p = 0.028).
      CONCLUSIONS: Arterial hypertension in non-obese women is associated with insulin
      resistance, central fat distribution and higher leptin levels.

PMID- 19578596
TI  - [Analysis of fingerstick capillary glycemia versus alternative site: Results and
      patients preferences].
AB  - This paper evaluate the efficacy and patients preferences of glucose monitoring
      in alternatives sites: ear lobe, forearm and calf against conventional
      fingerstick. We studied 89 patients (39 M/ 50 F) with type 2 diabetes mellitus
      (DM2). Glucose monitoring was measured using a digital glucosimeter (ACCU - CHEK
      Performa, Roche), and ACCU-CHEK Multiclix lancetador, with grade 5 on the distal
      phalange on the right hand's third finger, inferior part of right ear lobe, right
      forearm and right calf. There was not statistical significance on the comparative
      analyzes of fingerstick and alternatives sites. There was more pain in
      fingerstick. The patients preferred the fingerstick and the ear lobe. Glucose
      monitoring in alternative sites is as simple, safe and efficient as fingerstick.

PMID- 19578597
TI  - [Periodontal status in children and adolescents with type 1 diabetes mellitus].
AB  - OBJECTIVE: To evaluate periodontal condition of diabetic children and its related
      factors. METHODS: The plaque index (PI), sites with bleeding on probing (BOP),
      probing depth (PD) and clinical attachment level (CAL) were evaluated in all
      occlusion permanent teeth of 168 non smoking type 1 diabetic children, 13 +/- 3.5
      years old. The PI and BOP evaluations were also performed in deciduous teeth.
      RESULTS: It was observed a prevalence of 20.8% of gingivitis and 5.9% of
      periodontitis. Those individuals with poor metabolic control had higher
      percentage of affected sites on PD (p = 0.004) and on CAL (p = 0.014). Patients
      having more than five years with diabetes mellitus type 1 showed higher
      percentual of affected sites on PD (p = 0.002), on BOP (p < 0.001) and on CAL (p
      = 0.007). CONCLUSIONS: DM1 duration and poor glycemic control were significantly
      associated with periodontal disturbances suggesting higher susceptibility of this
      population in developing DP.

PMID- 19578598
TI  - [Diabetes immersion training as teaching method to medical practitioners].
AB  - This study evaluated the effectiveness of theoretical and practical teaching
      method in diabetes and doctors' position about feasibility of intensive blood
      glucose control. Forty-eight internal medicine or endocrinology residents
      participated in a two-day diabetes immersion course. The participants received
      training on self-blood glucose monitoring, techniques of insulin administration
      and carbohydrate counting. They were also instructed to behave as patients with
      diabetes and to follow individual medical prescription. They were assessed
      through questionnaires. In knowledge assessment, a significant increase of 12%
      was observed between the beginning and the end of the course (61.2% and 73.2%,
      respectively, with p < 0.0001). Before the course, 70.8% and 89.6% of the
      participants believed there were complications in performing carbohydrate
      counting and blood glucose monitoring, respectively. After the experience, 82.9%
      of them had difficulties in carbohydrate counting and 80.8% in self-monitoring;
      40.4% took all medications prescribed and 36.1% monitored blood glucose
      correctly. These results show that the methodology of this course is an effective
      way to disseminate knowledge and that it contributes to doctors becoming more
      sensitive to daily problems faced by patients with diabetes melito concerning the
      acceptance of medical recommendations.

PMID- 19578599
TI  - [Reliability of the classification of nutritional status obtained through the BMI
      and three different methods of body fat percentage in patients with type 1
      diabetes mellitus].
AB  - OBJECTIVE: To assess the reliability of classification of nutritional status (NS)
      obtained through the body mass index (BMI) and three different methods of body
      composition (BC) in individuals type 1 diabetics (T1D) and non-diabetic subjects.
      METHODS: 84 patients with T1D and 37 controls were evaluated. Anthropometric data
      was collected to calculate BMI and assessment of BC was performed through the
      methods of skinfold thickness (SF), bipolar (BI) and tetrapolar (TT)
      bioelectrical impedance. The agreement between the scores of each method was
      determined by Kappa (K) coefficient. RESULTS: Considering all the patients, only
      48 (57.1%) presented classification of BMI that agreed with the SF method, 58
      (69%) with the BI and 45 (53.5%) with the TT. The K results for individuals with
      T1D was DC = 0.261, BI = 0.320 and TT = 0.174. The controls had higher values (DC
      = 0.605, BI = 0.360 and TT = 0.400). However, all values were considered low.
      CONCLUSIONS: The method of BMI showed little sensitivity to BC changes in
      patients with T1D. Appropriated methods for the assessment of BC should be used
      to classify the NS of this population.

PMID- 19578600
TI  - Type 1 diabetes susceptibility determined by HLA alleles and CTLA-4 and insulin
      genes polymorphisms in Brazilians.
AB  - INTRODUCTION: Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in
      which genetic and environmental aspects are important to its development. The
      association of genetic variations with disease has been demonstrated in several
      studies; however, the role of some gene loci has not yet been fully elucidated.
      OBJECTIVE: To compare the frequency of HLA alleles and polymorphism in CTLA-4 and
      insulin genes in Brazilians with T1ADM and individuals without the disease, as
      well as to identify genetic markers that are able to discriminate between
      diabetic and non-diabetic individuals. METHODS: The presence of HLA DQB1, DQA1
      and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and
      49 A/G in the CTLA-4 gene were identified by the 'Time-resolved fluorometer'
      technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb
      (III). RESULTS: The DQB1 *0302 and DQA1 *03 alleles were identified as
      predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect
      against the disease.The DQA1 label proved to be able to differentiate between
      71.13% of the diabetic and non-diabetic individuals.This value increased to
      82.47% when the DQB1 label was added. No significant difference in the frequency
      of polymorphisms in the insulin and CTLA-4 genes was observed between the two
      groups. CONCLUSIONS: The genetic markers that best characterized and
      discriminated diabetic and non-diabetic individuals were the HLA DQA1 and
      DQB1.alleles.

PMID- 19578601
TI  - [Necrotizing vasculitis as a manifestation of hypersensitivity to
      propylthiouracil].
AB  - Propylthiouracil (PTU), a thyonamide class drug commonly used to treat
      hyperthyroidism has been reported to cause adverse reactions in 3% to 12% of
      patients. The side effects have been described more frequently as mild, but
      ocasionally severe fatal reactions may occur. We report the case of a fourteen
      years old patient in use of PTU for the last three years who presented with
      fever, hemorrhagic blisters, necrotic ulcers, and that developed purpuric lesions
      and nodules in lower extremities. Laboratory and histopathologic findings were
      compatible with skin leukocytoclastic vasculitis, a pattern found in
      hypersensitivity reaction vasculitis. Suspension of PTU and introduction of
      prednisone, induced complete remission of symptoms and healing of the skin
      lesions. The importance of this study is to call attention to the occurrence of
      serious cutaneous manifestation with a mortality rate that might reach 10%,
      associated with a systemic drug frequently used in internal medicine. Early
      diagnosis and withdrawal of the suspected medication is mandatory. Administration
      of corticosteroids and/or immunosuppressives agents must be considered.

PMID- 19578602
TI  - Tumor-induced osteomalacia: a case report.
AB  - Tumor-induced osteomalacia (TIO) is a rare paraneoplasic syndrome with
      overproduction of fibroblast growth factor 23 as a phosphaturic agent, leading to
      chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately
      normal or low levels of 1,25-dihydroxyvitamin D. Diagnosis of this disease is
      often challenging. The following case report described a middle-aged man with
      symptoms of bone pain and severe muscle weakness, who was found to have TIO. The
      tumor responsible for the symptoms was localized on his thigh and its resection
      resulted in normalization of blood chemistry and complaints. Subsequent
      microscopic examination revealed a phosphaturic mesenchymal tumor, mixed
      connective tissue type. The authors reinforce the importance of recognition of
      this disease, as severe disability and even death can be avoided with the
      surgical removal of the causative tumor.

PMID- 19578603
TI  - Fenofibrate-induced rhabdomyolysis in a patient with chronic kidney disease: an
      unusual presenting feature of hypothyroidism.
AB  - Clinical and most often moderate skeletal muscle involvement is a frequent
      problem in adults with hypothyroidism, and includes a number of different
      manifestations. Severe involvement with rhabdomyolysis, however, is very rare,
      and only a few cases have been reported to date, most of them with an additional
      factor of muscle injury. We described a patient with stage 3 chronic kidney
      disease who presented with rhabdomyolysis while taking fenofibrate, and was found
      to have hypothyroidism. We also highlighted the importance of excluding the
      diagnosis of thyroid dysfunction before treatment with lipid-lowering agents.

PMID- 19578605
TI  - [Virtual colonoscopy, colonic polyps and acromegaly].

PMID- 19578606
TI  - [The importance of evidence-based medicine concepts for the clinical
      practitioner].
AB  - The acceptance or refusal of new therapies and technologies pose a formidable
      problem for the daily practice of the gastroenterologist. It is of utmost
      importance to adopt clear strategies to select the true evidences from the huge
      amount of new medical information. Gathering fundamental concepts of clinical
      epidemiology and medical informatics, evidence-based medicine (EBM) build up
      those strategies keeping the patient as the main objective of its application.
      The evidence-based medicine movement values the randomized controlled clinical
      trials, with adequate sample size and clear and valid outcomes. Facing
      conflicting results from those trials, evidence-based medicine values the
      systematic review and whenever possible its statistical counterpart, the meta
      analysis. Evidence-based medicine provides valuable tools for the ethic and less
      subjective incorporation of new treatments and technologies in gastroenterology.

PMID- 19578607
TI  - Performance of computed tomographic colonography for the screening of colorectal
      polyp in acromegalic patients: a prospective study.
AB  - CONTEXT: Acromegalic patients have better chances to develop colorectal polyps
      and cancer and, considered a high-risk group, need to undergo frequent screening
      examinations. Moreover, in acromegalia, the increased bowel length and the
      intestinal loop complexity can lead to higher levels of technical difficulties
      and increase the risks of complications at conventional colonoscopy. Computed
      tomographic colonography, also known as virtual colonoscopy, is an innovative and
      secure technology which is revolutionizing the diagnosis of colon and rectum
      neoplasias. OBJECTIVE: To analyze computed tomographic colonography performance
      for the screening of colorectal polyps in acromegalic patients. METHODS: A
      prospective study of 21 asymptomatic acromegalic patients, 12 male and 9 female,
      average age 49, who underwent computed tomographic colonography and conventional
      colonoscopy. Computed tomographic colonography was performed with a GE Helical
      Multislice Computed Tomography Apparatus. Conventional colonoscopy was performed
      in the same day, without previous knowledge of the computed tomographic
      colonography diagnostics. The study evaluated the capacity of computed
      tomographic colonography to detect patients with colorectal polyps and identify
      each colorectal lesion described by the colonoscopy. RESULTS: In two patients
      (2/21), conventional colonoscopy was incomplete. However, in all patients
      computed tomographic colonography was complete. In Phase I ('per patient'),
      computed tomographic colonography diagnosed eight of the nine patients with
      colorectal polyps and showed 88% sensitivity, 75% specificity and 81% accuracy.
      In Phase II ('per polyp'), out of the 21 acromegalic patients included in this
      study, 12 presented normal findings at conventional colonoscopy. A total of 19
      polyps were identified in 9 patients. Ten of the 19 polyps were smaller than 10
      mm, and 9 were equal to or larger than 10 mm. Computed tomographic colonography
      identified 7 of the 9 polyps >10 mm described by conventional colonoscopy and
      only 6 of the 10 small polyps identified at conventional colonoscopy were
      detected by computed tomographic colonography. The histological analysis of
      resected lesions revealed 12 tubular adenomas, 6 hyperplastic polyps and 1
      colonic tubulo-villous adenoma with an adenocarcinoma focus. CONCLUSION: The
      authors present the first reports of computed tomographic colonography in the
      screening of colorectal polyps in acromegalic patients. In this study, computed
      tomographic colonography was performed without complications and a complete and
      safe colorectal evaluation was possible in all acromegalic patients. Moreover,
      computed tomographic colonography presented good sensitivity, specificity and
      accuracy for the identification of acromegalic patients with polyps of any size
      and better results in the diagnosis of large polyps, when they were compared to
      small polypoid lesions.

PMID- 19578608
TI  - Seroprevalence of Helicobacter pylori in patients with colon adenomas in a
      Brazilian university hospital.
AB  - CONTEXT: The association between Helicobacter pylori infection and colon
      neoplasia has been the subject of recent investigations which have produced
      controversial results. OBJECTIVE: To evaluate the prevalence of H. pylori
      infection in patients with colonic adenomas and also in patients whose
      colonoscopy exams were normal. METHODS: After colonoscopy, the individuals were
      distributed into two groups: patients with colon adenomas (cases) and patients
      whose colons were normal (controls). The groups were similar regarding age and
      gender. The individuals of both groups were subjected to a dosage of IgG antibody
      against H. pylori. The dosage was applied according to the solid phase,
      chemiluminescent immunometric assay. The chi-square test was used to analyze the
      data. RESULTS: There were 30 men and 64 women in each group (94 cases and 94
      controls). The mean age of the cases was 59.79 +/- 12.25 years and that of the
      controls was 58.98 +/- 11.55 years. The H. pylori serology was positive for 66
      (70.21%) of the cases and for 51 (54.25%) of the controls. There was a
      significant difference (P = 0.024). The odds ratio was 1.98 (CI 95%, 0.82-3.15).
      The prevalence of H. pylori in cases and controls according to gender,
      histological type and location of the colon lesions showed a significant
      difference only among women (P = 0.03), among patients with tubular adenomas (P =
      0.03), and in those with distal adenomas (P = 0.038). CONCLUSION: There is a
      positive association between H. pylori infection and colonic adenomas. This
      association is more evident in women, especially for tubular adenomas and distal
      colonic location.

PMID- 19578609
TI  - Terminal ileum of patients who underwent colonoscopy: endoscopic, histologic and
      clinical aspects.
AB  - CONTEXT: For the diagnosis of the diseases which affect the terminal ileum, the
      colonoscopy allows macroscopic evaluation and the performing of biopsies. Studies
      with criteria for the endoscopic and histological characterization of this
      segment are scarce and there are still some doubts about the need of biopsies in
      patients with normal ileoscopy. OBJECTIVE: Study the terminal ileum of patients
      who underwent colonoscopy considering: endoscopic and histological correlation;
      agreement between results of the initial histological evaluation and slides
      review, and the chance of subjects with normal ileoscopy with abdominal pain
      and/or chronic diarrhea to show histological alterations. METHODS: In a
      prospective study, 111 patients who presented smooth mucosa without enanthema in
      the endoscopic exam of the terminal ileum were selected. Biopsies of the ileal
      mucosa of such patients were performed, being the slides routinely examined and
      reviewed afterwards. RESULTS: The correlation between patients with normal
      ileoscopy and ileum with preserved histological architecture was of 99.1%. The
      agreement between initial histological evaluation and slides review calculated by
      the Kappa test was 0.21. In patients with abdominal pain and/or chronic diarrhea,
      the chance of showing histological alterations was 2.5 times higher than the
      others. CONCLUSIONS: The correlation between endoscopic and histological findings
      was high. The agreement between the initial histologic evaluation and slides
      review was not satisfactory. The chance of subjects with normal ileoscopy with
      abdominal pain and/or chronic diarrhea, showing histological alterations was
      higher in relation to the asymptomatic ones or with other symptoms, although the
      clinical importance of this datum was not evaluated.

PMID- 19578610
TI  - Morphometric digital measurement of the luminal opening area of colonic crypts
      (pits) can differentiate the adenomas from other colonic lesions.
AB  - CONTEXT: Differential diagnosis of hyperplastic vs adenomatous lesions is of
      crucial importance on the daily practice of colonoscopy. OBJECTIVES: This study
      aimed at quantifying digital morphometric characteristics of colonoscopic images
      obtained with magnification and chromoscopy of three different types of colonic
      lesions: hyperplastic, adenomas and carcinomas, and the normal mucosa surrounding
      the lesions. METHODS: A total of 2,177 consecutive colonoscopies were analyzed
      and 105 images were chosen for analysis, divided into 37 hyperplastic lesions, 42
      adenomas and 26 carcinomas. Specific digital morphometry was used, to measure the
      diameter and area of the pits from hyperplastic lesions, adenomatous and
      carcinomatous lesions, always comparing them with the normal mucosa surrounding
      pits. RESULTS: Different morphometric measures were performed via image analysis
      software to measure the mean pit opening diameters and their respective area. The
      mean pit opening diameters and corresponding area measurements were statistically
      significant for all groups of lesions examined. CONCLUSIONS: The morphometric
      characteristics of colonoscopy images allowing the observer to compare
      differences between hyperplastic and adenomatous polyps and colorectal carcinoma
      lesions. Digital morphometric studies are feasible like the present study shows.
      This can help the colonoscopist in clinical decisions. A software with
      morphometric measures can apply and will permit the digital morphometric
      analysis. The data generated from the application of software, can provide
      valuable points in differentiation of various lesions, guiding the conduct
      clinical, already during the endoscopic procedure. Morphometric analysis is more
      an instance of decision to the colonoscopist and it has important value not for
      being subjective, but for being objective, since it generates digits of its
      measures. In these aspects, and among different characteristics, the measure of
      the area showed to be the most important measure in the differential aspect.
      Different lesions have different patterns of morphometric measures and theses
      patterns can be obtained from the study of the characteristics in databases. The
      endoscopic removal of adenomatous polyps (polypectomy), or a more detailed study
      of the neoplastic lesions for helping the decision if endoscopic removal
      (mucosectomy) or surgical resection, and a conservative position in hyperplastic
      lesions, are proceedings that morphometrics, with another parameters, can help to
      decide.

PMID- 19578611
TI  - [Comparative study between MBI (FICE) and magnification chromoendoscopy with
      indigo carmine in the differential diagnosis of neoplastic and non-neoplastic
      lesions of the colorectum].
AB  - CONTEXT: Multiband imaging (MBI)/Fuji Intelligent Color Enhancement (FICE) is a
      spectral image processing technology that helps in vivo diagnosis of colorectal
      neoplasias. OBJECTIVE: To compare the diagnostic accuracy of the magnification
      with either the electronic chromoendoscopy or indigo carmine dye in the
      differential diagnosis of neoplastic and non-neoplastic colorectal lesions.
      METHODS: Seventy five patients with 157 colorectal lesions were prospectively
      evaluated. The capillary pattern, as well as the pit pattern according to the
      Kudo classification, of colorectal lesions were evaluated by means of the FICE
      system. Absence and presence of meshed capillary networks were labeled as non
      neoplastic and neoplastic lesions, respectively. Afterwards, indigo carmine 0.8%
      was instilled and a new evaluation of the pit pattern was carried out. RESULTS:
      One hundred and sixteen of the 157 lesions were classified as positive meshed
      capillary network, 115 of them were confirmed histologically as neoplasia. Other
      32 lesions out of 41 with negative meshed capillary network were non-neoplastic.
      Sensitivity, specificity and accuracy were, respectively, 92.7%, 97% and 93.6%.
      Pit patterns I and II were confirmed as non-neoplastic lesions, and patterns III
      to V were confirmed as neoplasias. Sensitivity, specificity and accuracy for the
      electronic chromoendoscopy were, respectively, 94.4%, 97% and 94.9%. Meanwhile,
      the figures for the magnification with indigo carmine were, respectively, 97.6%,
      93.9% and 96.8%. CONCLUSIONS: Both methods, either the MBI/FICE system or the use
      of indigo carmine dye with magnification, achieved a high accuracy for the
      differential diagnosis between neoplastic and non-neoplastic colorectal lesions.

PMID- 19578612
TI  - Ki67 and p53 in gastrointestinal stromal tumors--GIST.
AB  - CONTEXT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal
      tumor. Cellular proliferation and apoptosis is gaining importance for predicting
      prognosis in several cancers. OBJECTIVE: To investigate the Ki67 and p53
      immunostaining in GISTs. METHODS: Specimens from 40 patients with GIST were
      assessed for immunohistochemical expression of Ki67 and p53. The tumors were
      divided according the risk of recurrence in two groups: I with high or
      intermediate risk and; II with low or very low risk. RESULTS: Among the 40
      patients, 21 were men, the mean age was 56 years, 16 occurred in the small
      intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or
      rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from
      group II. Half of the patients developed recurrence, being 90% of the group I (P
      = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level
      0.12). This index was marginally higher in the group I patients with recurrence
      (P = 0.09) compared to the patients of the same group without recurrence. p53
      staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67
      had been found in the group I tumors when compared to the other group (P = 0.022;
      OR = 8.00 - IC 95%: 1.32-48.65). CONCLUSION: The most common site was the small
      intestine and 80% had a malignant potential justifying the high recurrence
      observed. No significant correlation was found between p53 and overall outcome of
      the patients. In group I patients, the evaluation Ki67LI may be a marker of
      prognosis. The positivity of both markers is higher among the patients with worst
      prognosis than in the others.

PMID- 19578613
TI  - [Preoperative progressive pneumoperitoneum in voluminous abdominal wall hernias].
AB  - CONTEXT: Correction of voluminous hernias and large abdominal wall defects is a
      big challenge in surgical practice due to technical difficulties and the high
      incidence of respiratory and cardiovascular complications. OBJECTIVES: To present
      the authors experience with inducing progressive pneumoperitoneum preoperative to
      surgical treatment of voluminous hernias of the abdominal wall. METHODS:
      Retrospective study of six patients who presented voluminous hernias of the
      abdominal wall and were operated after installation of a pneumoperitoneum. The
      procedure was performed by placing a catheter in the abdominal cavity at the
      level of the left hypochondrium with ambient air insufflation for 10 to 15 days.
      RESULTS: Four of the six patients were female and two male. Ages ranged from 42
      to 62 years. Hernia duration varied from 5 to 40 years. Four patients had
      incisional, one umbilical, and one inguinal hernias. Mean pneumoperitoneum time
      was 11.6 days. There were no complications related to pneumoperitoneum
      installation and maintenance. All hernias were corrected without technical
      difficulties. The Lichtenstein technique was used to correct the inguinal hernia,
      peritoneal aponeurotic transposition for one of the incisional hernias, with the
      rest corrected using polypropylene mesh. One death and one wall infection were
      observed post operatively. No recurrences were reported until now, in 4 to 36
      months of follow-up. CONCLUSION: Preoperative progressive pneumoperitoneum is a
      safe and easy executed procedure, which simplifies surgery and reduces post
      operative respiratory and cardiovascular complications. It is indicated for
      patients with hernias that have lost the right of domain in the abdominal cavity.

PMID- 19578614
TI  - Immunoreactivity of cytokeratins 7 and 20 in goblet cells and columnar blue cells
      in patients with endoscopic evidence of Barrett's esophagus.
AB  - CONTEXT: Barrett's esophagus is characterized by the presence of goblet cells.
      However, when alcian-blue is utilized, another type of cells, called columnar
      blue cells, is frequently present in the distal esophagus of patients with
      endoscopic evidence of Barrett's esophagus. Cytokeratin 7 and 20 immunoreactivity
      has been previously studied in areas of intestinal metaplasia at the
      esophagogastric junction. However, the expression of these cytokeratins in
      columnar blue cells has not been characterized. OBJECTIVE: To compare the
      expression of cytokeratin 7 and 20 in goblet cells and columnar blue cells in
      patients with endoscopic evidence of Barrett's esophagus. METHODS: Biopsies from
      86 patients with endoscopic evidence of Barrett's esophagus were evaluated. The
      biopsies were stained for cytokeratin 7 and 20. RESULTS: Goblet cells were
      present in 75 cases and columnar blue cells in 50 cases. Overall, cytokeratin 7
      expression was similar in goblet cells and columnar blue cells (P = 0.25), while
      cytokeratin 20 was more common in goblet cells (P <0.001). In individuals with
      both cell types, however, cytokeratin 7 staining was the same in goblet and
      columnar blue cells in 95% of the cases, and cytokeratin 20 staining was the same
      in 77%. CONCLUSION: Goblet cells and columnar blue cells have similar
      immunohistochemical staining patterns for cytokeratins 7 and 20 in patients with
      endoscopic evidence of Barrett's esophagus.

PMID- 19578616
TI  - [Clinical and endoscopic outcome after Nissen fundoplication for gastroesophageal
      reflux disease].
AB  - CONTEXT: The surgical treatment of gastroesophageal reflux disease is indicated
      in patients with a chronic condition when proton pump inhibitors therapy is
      ineffective or when symptoms are persistently recurrent. Fundoplication failure
      occurrence has been detected in some patients and highlights a needing of
      monitoring esophageal post-surgical condition since that clinical symptoms are
      not sensitive enough for indicating fundoplication failure. AIMS: To identify the
      frequency of a disrupted wrap in the postoperative period and to evaluate
      esophageal complications related with gastroesophageal reflux recurrence in
      children and adolescents. METHODS: The study was cross-sectional, prospective and
      descriptive, including 45 patients (16 months-16.9 years) who had undergone
      Nissen fundoplication in a school hospital. Twenty six patients (57.8%) were
      neurologically impaired. Upper gastrointestinal endoscopy was performed in order
      to determine fundoplication integrity, endoscopic and histopathological
      esophageal condition. Upper gastrointestinal endoscopies were performed from 12
      up to 30 months after surgery. RESULTS: Patent wrap was identified in 41 patients
      (91.1%). Recurrent peptic esophagitis was found in 6 of 45 patients, 2 of which
      required a second fundoplication and other two had Barrett esophagus. Endoscopic
      peptic esophagitis was associated with a defective wrap (P = 0.005). Conclusions 
      Fundoplication was effective for treating esophagitis, even in patients with
      previous esophageal stenosis. Endoscopic follow up may detect surgery failure in
      children undergone anti-reflux surgery even in asymptomatic patients.

PMID- 19578615
TI  - [Alpha-interferon versus peg-interferon associated to ribavirin in the treatment
      of genotype 1 hepatitis C virus and human immunodeficiency virus coinfected
      patients].
AB  - CONTEXT: It has been suggested that coinfected patients HCV/HIV must be treated
      with pegylated interferon associated to ribavirin (PEG+RBV), because of better
      taxes of sustained virological response when compared to those treated with
      conventional interferon associated to ribavirin (IFN+RBV). There are few studies
      in the literature comparing these two treatments options in this population.
      OBJECTIVE: To evaluate the sustained virological response to the treatment with
      IFN+RBV versus PEG+RBV in coinfected patients HCV/HIV genotype 1, in a public
      health program. METHODS: It is a cohort study, where the data of the coinfected
      patients treated with IFN+RBV (before 2002) or PEG+RBV (from 2002) during 48
      weeks in the Brazilian Health Ministry program were reviewed. Demographic
      characteristics were evaluated (age, gender and weight), CD4 cell count and
      histopathology - inflammatory activity (A) and fibrosis grade, by METAVIR
      classification. The significance level adopted was 5%. RESULTS: Eighty one
      patients were evaluated, 22 treated with IFN+RBV and 59 treated with PEG+RBV.
      Both were similar relating to age, gender, weight, CD4 cell count and fibrosis
      grade. Those treated with IFN+RBV presented a greater proportion of A2+A3
      patients than those treated with PEG+RBV (P<0.01). The sustained virological
      response was 14% versus 23% in those using IFN+RBV or PEG+RBV respectively (P =
      0.54). The Odds Ratio was 1.9 (0.5 to 7.3). CONCLUSION: Coinfected patients
      HCV/HIV genotype 1 treated with PEG+RBV presented 1.9 more chance to obtain
      sustained virological response than those treated with IFN+RBV, however without
      statistical significance.

PMID- 19578617
TI  - Recalled and recorded bowel habits confirm early onset and high frequency of
      constipation in day-care nursery children.
AB  - CONTEXT: Mothers recall early-onset constipation in children attending
      gastroenterology clinics. OBJECTIVES: To study the bowel habit of young children
      in the community to determine, first, whether early-onset constipation is
      confirmed in this setting and, second, the agreement between recalled and
      recorded bowel habit. METHODS: Defecation data of 57 children aged 6.0-40.7 mo
      were obtained by maternal recall (questionnaire on predominant stool
      characteristics) and by record (1,934 defecations registered prospectively at
      home and in the nursery). The bowel habit was classified according to stool
      frequency and proportion of stool characteristics (soft, hard and/or runny). Two
      criteria were used to classify recorded data, since the cutoff point for hard
      stools to identify constipation is undefined in children: predominant criterion
      and adult criterion, respectively with >50% and >25% of stools with altered
      consistency. Bowel habit categories were: adequate, constipation, functional
      diarrhea and 'other bowel habit'. Nonparametric statistics, and the Kappa index
      for agreement between recalled and recorded bowel habit, were used. RESULTS:
      Constipation occurred in 17.5%, 10.5%, 19.3% of the children by recall, the
      predominant and the adult criteria, respectively. Constipation was the main
      recalled alteration, vs 12.3% 'other bowel habit'. Only one child classified as
      having functional diarrhea (by the adult criterion). Agreement between recalled
      and recorded bowel habit was fair for constipation, by the predominant and the
      adult criteria (K = 0.28 and 0.24, respectively), but only slight (K <0.16) for
      other bowel habit categories. Individual data, however, pointed to a better
      relationship between recalled constipation and the adult rather than the
      predominant criterion. CONCLUSIONS: Frequent early-onset constipation was
      confirmed. Fair agreement between recalled and recorded constipation by the two
      used criteria indicates that recalled data are quite reliable to detect
      constipation.

PMID- 19578618
TI  - En-bloc pancreatoduodenectomy and right hemicolectomy for treating locally
      advanced right colon cancer (T4): a series of five patients.
AB  - A series of five cases of right-colon adenocarcinoma that invaded the proximal
      duodenum is presented. All patients underwent successful en-bloc
      pancreatoduodenectomy plus right hemicolectomy by General Surgery Service of the
      Teaching Hospital of the ABC Medical School, Santo Andre, SP, Brazil. The study
      was conducted between 2000 and 2007. There were two major complications but no
      mortality. Three patients did not present any recurrence over the course of 15 to
      54 months of follow-up. Multivisceral resection with en-bloc
      pancreatoduodenectomy should be considered for patients who are fit for major
      surgery but do not present distant dissemination. Long-term survival may be
      attained.

PMID- 19578619
TI  - [Contraception and pregnancy after liver transplantation: an update overview].
AB  - CONTEXT: Successful liver transplantation not only treats the underlying liver
      disease but also restores libido and fertility in female recipients. Although
      reports of successful pregnancy after liver transplantation continue to increase,
      these pregnancies are considered of high-risk because they are associated with
      increase maternofetal morbidity. EVIDENCE ACQUISITION: A MEDLINE search (1978
      2007) was conducted using the terms 'liver transplantation', 'pregnancy',
      'immunosuppressive agents', 'sexual function'. Reviews, retrospective series,
      long-term clinical follow-up of case series and original articles containing
      basic scientific observations were included. RESULTS: Although no formal
      guidelines have been established there are some 'golden rules' to improve the
      probability of favorable maternal and fetal outcome. Most transplant centers
      recommend to delay pregnancy for at least 1-year after transplantation. The
      recipient should be on a stable immunosuppression regimen, with good graft
      function and no evidence of renal dysfunction or uncontrolled arterial
      hypertension. Considering the increased incidence of prematurity, low birth
      weight, hypertension and preeclampsia reported during pregnancy post-LT, these
      high-risk patients should be managed by a multidisciplinary team, including an
      obstetrician specialized in high-risk pregnancies. Carefully monitoring of
      immunosuppressive drugs serum level is prudent to avoid graft rejection episodes
      and drugs with teratogenic potential should be discontinued. Breastfeeding is
      usually not recommended. CONCLUSIONS: Successful pregnancies are the rule after
      liver transplantation. A carefully monitoring by an experience multidisciplinary
      team increases the chances of favorable maternofetal outcome.

PMID- 19578620
TI  - Blastocystis infection in patients with chronic renal disease.

PMID- 19578621
TI  - Clinical, endoscopic and prognostic aspects of primary gastric non-hodgkin's
      lymphoma associated with acquired immunodeficiency syndrome.
AB  - Primary gastric non-Hodgkin's lymphoma (NHL) is a co-morbidity that can be
      observed during the clinical course of acquired immunodeficiency syndrome (AIDS).
      We evaluated the prevalence, clinical-evolutive aspects and form of endoscopic
      presentation of primary gastric NHL associated with AIDS. Two hundred and forty
      three HIV patients were submitted to upper digestive endoscopy, with evaluation
      of clinical, endoscopic and histological data. A CD4 count was made by flow
      cytometry and viral load was determined in a branched-DNA assay. Six cases (five
      men; mean age: 37 years; range: 29-46 years) of primary gastric NHL were
      detected. The median CD4 count was 140 cells/mm(3) and the median viral load was
      40,313 copies/mL. Upper digestive endoscopy revealed polypoid (in four patients)
      ulcero-infiltrative (two patients) and ulcerated (two patients) lesions and
      combined polypoid and ulcerated lesions (two patients). Histology of the gastric
      lesions demonstrated B cell NHL (four patients) and T cell NHL (two patients).
      Five of the six patients died of complications related to gastric NHL. We
      concluded that primary gastric NHL is an important cause of mortality associated
      with AIDS.

PMID- 19578622
TI  - Frequency of mental disturbances in HTLV-1 patients in the state of Bahia,
      Brazil.
AB  - Viral infections and chronic diseases have been associated with psychiatric
      disorders. Among these, increased depression has been reported in HTLV-1
      patients. However, no studies on the prevalence of other mental disturbances have
      been carried out in these patients. Salvador is the city with the highest rate of
      infection with HTLV-1 in Brazil and it is estimated that approximately 40,000
      inhabitants are infected. In our cross sectional study, we examined the frequency
      of mental disturbances in 50 HTLV-1 seropositive patients followed at the Centro
      Integrativo e Multidisciplinar de HTLV e Hepatites Virais (CHTLV) of the Escola
      Bahiana de Medicina e Saude Publica (EBMSP) in Salvador from January to November
      2007. We used a questionnaire to collect clinical-epidemiologic data and the Mini
      International Neuropsychiatric Interview Brazilian Version 5.0.0 (M.I.N.I.) to
      evaluate the psychiatric disorders. The Statistical Package for Social Sciences
      (SPSS) was used for the analyses. Twenty-one (42%) HTLV-1 patients had a
      psychiatric co-morbidity; 17(34%) had mood disorders, 11 (22%) were anxious and
      one (2%) was an alcoholic. We found a high frequency of mental disturbances among
      HTLV-1 infected individuals, suggesting a possible association of this infection
      with psychiatric diseases.

PMID- 19578623
TI  - Estimating HIV-1 incidence using the serologic testing algorithm for recent HIV
      infections at HIV counseling and testing centers in the city of Sao Paulo,
      Brazil.
AB  - The network of HIV counseling and testing centers in Sao Paulo, Brazil is a major
      source of data used to build epidemiological profiles of the client population.
      We examined HIV-1 incidence from November 2000 to April 2001, comparing
      epidemiological and socio-behavioral data of recently-infected individuals with
      those with long-standing infection. A less sensitive ELISA was employed to
      identify recent infection. The overall incidence of HIV-1 infection was
      0.53/100/year (95% CI: 0.31-0.85/100/year): 0.77/100/year for males (95% CI: 0.42
      1.27/100/year) and 0.22/100/ year (95% CI: 0.05-0.59/100/year) for females.
      Overall HIV-1 prevalence was 3.2% (95% CI: 2.8-3.7%), being 4.0% among males (95%
      CI: 3.3-4.7%) and 2.1% among females (95% CI: 1.6-2.8%). Recent infections
      accounted for 15% of the total (95% CI: 10.2-20.8%). Recent infection correlated
      with being younger and male (p = 0.019). Therefore, recent infection was more
      common among younger males and older females.

PMID- 19578624
TI  - Xerostomy, dental caries and periodontal disease in HIV+ patients.
AB  - We studied xerostomy and its correlation with periodontal and dental cavity
      diseases in HIV patients, through measurement of salivary flow and through
      variables such as saliva buffer capacity, salivary pH, periodontal index, MDF
      index, dental carie risk and risk of periodontal disease. One hundred patients
      were analyzed. They were distributed into two groups: Group I (test) - 50
      patients evidently HIV+, from whom information was collected and analyzed
      regarding age, gender, skin color, habits, general and oral diseases, levels of T
      CD4 lymphocytes, viral load and highly active antiretroviral therapy (HAART); and
      Group II - (control) 50 HIV- patients, from whom information was collected and
      analyzed regarding age, gender, skin color, habits, general and oral diseases. In
      both groups, measurement of salivary flow, pH and buffer capacity was made. Group
      I presented high MDF, bacteria plaque and bleeding, with a greater susceptibility
      to the risks of oral cavities and periodontal disease. The salivary flow and the
      buffering capacity of the saliva were low, indicating a high level of xerostomy.
      Two important modifying factors influence these pathologies in an incisive way:
      one is immunossuppression and the other is HAART therapy. The control exhibited
      results that are closer to normality; it had better oral-health conditions.

PMID- 19578625
TI  - Neurotoxoplasmosis diagnosis for HIV-1 patients by real-time PCR of cerebrospinal
      fluid.
AB  - Encephalitis caused by Toxoplasma gondii is the most common cause of central
      nervous system damage in patients with acquired immunodeficiency syndrome (AIDS).
      Toxoplasma may infect any of the brain cells, thus leading to non-specific
      neurotoxoplasmosis clinical manifestations including focused or non-focused signs
      and symptoms of central nervous system malfunction. Clinical development ranges
      from insidious display during weeks to experiencing acute general confusion or
      ultimately fatal onset. Cerebral toxoplasmosis occurs in advanced stages of
      immunodeficiency, and the absence of anti-toxoplasmosis antibodies by the
      immunofluorescence method does not allow us to rule out its diagnosis. As
      specific therapy begins, diagnosis confirmation is sought through clinical and
      radiological response. There are few accurate diagnosis methods to confirm such
      cases. We present a method for T. gondii DNA detection by real time PCR
      Multiplex. Fifty-one patients were evaluated; 16 patients had AIDS and a
      presumptive diagnosis for toxoplasmosis, 23 patients were HIV-positive with
      further morbidities except neurotoxoplasmosis, and 12 subjects were HIV-negative
      control patients. Real time PCR-Multiplex was applied to these patients'
      cephalorachidian liquid with a specific T. gondii genome sequence from the 529bp
      fragment. This test is usually carried out within four hours. Test sensitivity,
      specificity, positive predictive value, and negative predictive value were
      calculated according to applicable tables. Toxoplasma gondii assay by real time
      Multiplex of cephalorachidian fluid was positive for 11 out of 16 patients with
      AIDS and a presumptive diagnosis for cerebral toxoplasmosis, while none of the 35
      control patients displayed such a result. Therefore, this method allowed us to
      achieve 68.8% sensitivity, 100% specificity, 100% positive predictive value, and
      87.8% negative predictive value. Real time PCR on CSF allowed high specificity
      and good sensitivity among patients who presumably had cerebral toxoplasmosis.
      Since this is a low invasive method, it could be included in the diagnosis
      algorithm of patients with AIDS and central nervous system damage.

PMID- 19578626
TI  - Structure-function analysis of two variants of mumps virus hemagglutinin
      neuraminidase protein.
AB  - A point mutation from guanine (G) to adenine (A) at nucleotide position 1081 in
      the hemagglutinin-neuraminidase (HN) gene has been associated with neurovirulence
      of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid
      (E) to lysine (K) change at position 335 in the HN glycoprotein. We have
      experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and
      HN-G1081) differ in neurotropism, sialic acidbinding affinity and neuraminidase
      activity. In the present study, we performed a structure-function analysis of
      that amino acid substitution; the structures of HN protein of both Urabe AM9
      strain variants were predicted. Based on our analysis, the E/K mutation changes
      the protein surface properties and to a lesser extent their conformations, which
      in turn reflects in activity changes. Our modeling results suggest that this E/K
      interchange does not affect the structure of the sialic acid binding motif;
      however, the electrostatic surface differs drastically due to an exposed short
      alpha helix. Consequently, this mutation may affect the accessibility of HN to
      substrates and membrane receptors of the host cells. Our findings appear to
      explain the observed differences in neurotropism of these vaccine strains.

PMID- 19578627
TI  - Genotypes and clinical data of respiratory syncytial virus and metapneumovirus in
      brazilian infants: a new perspective.
AB  - The aim of this study was to determine if there was a correlation between
      respiratory syncytial virus (RSV) and metapneumovirus (MPV) genotypes and
      clinical data of Brazilian infants hospitalized for acute lower respiratory
      infection. The viruses in the patients' nasopharyngeal secretions were studied
      using the polymerase chain reaction and phylogenetic analysis. The study assessed
      144 infants; 31.9% were RSV positive and 5.6% were MPV positive. Statistical
      analysis was performed using the chi-squared test, Fisher's test, Odds ratio,
      univariate logistic regression, non-conditional multivariate logistic regression
      and the forward - stepwise method. Multivariate analysis confirmed a significant
      relationship between a positive PCR test for RSV and hospitalization during the
      month of May and with pulse oximetry less than 90%. The phylogenetic analysis
      indicated the genotypes GA2, GA5, SAA1 (Group A), SAB1, SAB3 and BA (Group B) for
      RSV and Group B, subgroup B1, for MPV.

PMID- 19578628
TI  - Impact of psychiatric disorders on the quality of life of brazilian HCV-infected
      patients.
AB  - The aim of our study was to determine the impact of psychiatric comorbidities on
      the health-related quality of life of HCV-infected patients. Assessment of
      clinical, socio-demographic and quality of life data of the patients followed up
      at a Hepatology unit was performed by using a standard questionnaire and the SF
      36 instrument. Psychiatric diagnoses were confirmed by using the Mini
      International Neuropsychiatric Interview, Brazilian version 5.0.0 (MINI Plus).
      Evaluation using the MINI plus demonstrated that 46 (51%) patients did not have
      any psychiatric diagnosis, while 44 (49%) had at least one psychiatric diagnosis.
      Among patients with a psychiatric comorbidity, 26 (59.1%) had a current mental
      disorder, out of which 22 (84.6%) had not been previously diagnosed. Patients
      with psychiatric disorders had lower scores in all dimensions of the SF-36 when
      compared to those who had no psychiatric diagnosis. Scores of physical
      functioning and bodily pain domains were lower for those suffering from a current
      psychiatric disorder when compared to those who had had a psychiatric disorder in
      the past. Females had lower scores of bodily pain and mental health dimensions
      when compared to males. Scores for mental health dimension were also lower for
      patients with advanced fibrosis. The presence of a psychiatric comorbidity was
      the variable that was most associated with the different scores in the SF-36,
      compared to other variables such as age, gender, aminotransferase levels, and
      degree of fibrosis.

PMID- 19578629
TI  - Increased levels of IL-10, IL-12, and IFN- in patients with visceral
      leishmaniasis.
AB  - Visceral leishmaniasis remains a serious public health problem in developing
      countries. Cytokines have a crucial role in the pathogenesis of this disease. We
      evaluated plasma levels of IL-10, IL-12 and IFN- in 32 patients with active
      visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal
      individuals in an endemic area to look for correlations between the clinical
      outcome of infection and the plasma cytokine levels. An analysis was made with a
      skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with
      the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were
      significantly higher in the patients than in the control groups. We concluded
      that normalization of the plasma level of IFN- can serve as a reliable parameter
      for considering the patient as cured.

PMID- 19578630
TI  - Comparison of serological and parasitological methods for cutaneous leishmaniasis
      diagnosis in the state of Parana, Brazil.
AB  - We evaluated the effectiveness of serological and parasitological methods for
      cutaneous leishmaniasis (CL) diagnosis in patients from the central region of
      Parana state, southern Brazil. Five groups were compared: clinical diagnosis,
      parasitological diagnosis, communicants, inhabitants of a non-endemic area and
      carriers of other etiologies. Two antigens were prepared from promastigotes of
      Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis for
      indirect immunofluorescence assay, ELISA and immunoblotting. The parasitological
      approaches detected 79.3% of the patients with a clinical diagnosis; the
      parasites were identified by PCR as L. (V.) braziliensis. Serological methods
      showed 95% sensitivity for homologous antigens. Immunoblotting revealed specific
      proteins for diagnosis of CL and detected 96.6% of the patients when L. (V.)
      braziliensis was used as an antigen, and 83.3% with L. (L.) amazonensis. This
      study demonstrated the importance of differential diagnosis for leishmaniasis;
      the association of two or more indirect methods increased diagnosis sensitivity.

PMID- 19578631
TI  - A study of IgA antibody response to different mycobacterium tuberculosis antigens
      in the diagnosis and monitoring of pulmonary tuberculosis.
AB  - We evaluated the performance of the ELISA technique in the detection of IgA
      antibodies against different Mycobacterium tuberculosis antigenic preparations in
      serum samples from 49 patients with pulmonary tuberculosis collected before and
      after the start of specific treatment. The controls consisted of serum samples
      from healthy patients without any prior contact with the bacteria and serum
      samples from patients with other pneumopathies. Glycolipid antigen gave the best
      diagnostic performance, with a sensitivity of 88% and specificities varying from
      88 to 100% in the control groups. These antigens constitute a powerful tool for
      the diagnosis and monitoring of patients with pulmonary tuberculosis.

PMID- 19578632
TI  - The public health implications of melioidosis.
AB  - Melioidosis, which is caused by the bacterium Burkholderia pseudomallei, is a
      potentially fatal tropical infection, little known outside its main endemic zone
      of Southeast Asia and northern Australia. Though it has received more attention
      in recent years on account of its claimed suitability as a biological weapon
      agent, the principal threat from melioidosis is a result of naturally occurring
      events. Occasional case clusters, sporadic cases outside the known endemic zone
      and infections in unusual demographic groups highlight a changing epidemiology.
      As melioidosis is the result of an environmental encounter and not person-to
      person transmission, subtle changes in its epidemiology indicate a role
      environmental factors, such as man-made disturbances of soil and surface water.
      These have implications for travel, occupational and tropical medicine and in
      particular for risk assessment and prevention. Practical problems with definitive
      laboratory diagnosis, antibiotic treatment and the current lack of a vaccine
      underline the need for prevention through exposure avoidance and other
      environmental health measures. It is likely that the increasing population burden
      of the tropical zone and extraction of resources from the humid tropics will
      increase the prevalence of melioidosis. Climate change-driven extreme weather
      events will both increase the prevalence of infection and gradually extend its
      main endemic zone.

PMID- 19578633
TI  - Description of an HIV-1 BC recombinant virus identified in a pediatric patient in
      the city of Sao Paulo.
AB  - This case report refers to a 10-year-old HIV-1 infected patient, who was found to
      harbor a BC recombinant virus. This child lives in Sao Paulo and was infected by
      the mother-to-child route. Phylogenetic analyses revealed that this mosaic virus
      shares common breakpoints in the polymerase region with the recently published
      CRF31_BC.

PMID- 19578634
TI  - Vertical transmission of HIV and toxoplasma by reactivation in a chronically
      infected woman.
AB  - Prevention of mother-to-child transmission of HIV and Toxoplasma dual infections
      in the immunocompromised patient remains a healthcare challenge. We report a case
      of congenital toxoplasmosis resulting from reactivation of latent infection in a
      severely immunodepressed HIV-infected pregnant woman, who had poor adherence to
      therapy; this case illustrates the difficulties encountered in management of such
      a rare condition.

PMID- 19578635
TI  - Hemophagocytic syndrome associated with cytomegalovirus infection in a severely
      immunocompromised AIDS patient: case report.
AB  - Hemophagocytic syndrome is a clinical condition characterized by the infiltration
      of the bone marrow and reticuloendothelial system by macrophages and activated
      histiocytes, leading to uncontrolled phagocytosis of platelets, erythrocytes,
      lymphocytes and precursor cells. It is a severe inflammatory and aggressive
      condition, characterized by high fever, hepatosplenomegaly, lymphadenopathy and
      cytopenia, and it may lead to organ dysfunction. This syndrome is classified as
      familial or acquired; the latter is more frequent and is associated with diverse
      conditions, such as infections, malignancies and rheumatic diseases. We report a
      case of HLH associated with cytomegalovirus infection in a patient with acquired
      immunodeficiency syndrome and Burkitt's lymphoma.

PMID- 19578636
TI  - Acute acalculous cholecystitis in a teenager with hepatitis a virus infection: a
      case report.
AB  - Acute viral hepatitis A is a common systemic infection in children, especially in
      developing countries. Acute acalculous cholecystitis in the course of this
      infection is a rare and poorly reported event that needs to be diagnosed because
      of the possibility of complications, such as gangrene and perforation of the
      gallbladder wall. We present the case of a 16-year-old teenager with clinical and
      ultrasonographic findings of acalculous cholecystitis during an episode of
      hepatitis A virus infection, which took place December 2007 in Plantadores de
      Cana Hospital.

PMID- 19578637
TI  - Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: case
      report and literature review.
AB  - We report a case of severe hemolytic anemia following Mycoplasma pneumoniae
      infection in a 29-year-old male patient who was treated with azithromycin. Direct
      Coombs' test was strongly positive and the cold agglutinin titer was high, with
      anti-I specificity. Antimycoplasma antibody titer by complement fixation was high
      1:10,240. The patient was discharged after 12 days of hospitalization in good
      health. He remains clinically well with no recurrence of jaundice.

PMID- 19578638
TI  - Candida tropicalis in the peripheral blood of a surgical patient.

PMID- 19578639
TI  - Identifying reasons for failure in biomedical research and publishing.
AB  - The regular assessment of Brazilian scientific output means that individual
      university departments need to constantly improve the quantity and quality of
      their scientific output. A significant proportion of this output involves the
      work of Master's and Doctoral students, but getting this work published in a
      suitable journal can often prove to be a challenge. Although students' lack of
      fluency in English is a contributing factor, many of the problems observed have
      an early origin in the formulation of the research problem and its relevance to
      current research trends in the international literature. In short, more time
      needs to be spent in the library and less in the laboratory, and more effort
      needs to be made in teaching students basic research skills such as the effective
      use of bibliographic databases like PubMed, Web of Science and Scopus.

PMID- 19578640
TI  - Effect of postnatal malnutrition on hyperoxia-induced newborn lung development.
AB  - Several factors are associated with bronchopulmonary dysplasia. Among them,
      hyperoxia and lung immaturity are considered to be fundamental; however, the
      effect of malnutrition is unknown. Our objective was to evaluate the effects of 7
      days of postnatal malnutrition and hyperoxia on lung weight, volume, water
      content, and pulmonary morphometry of premature rabbits. After c-section, 28-day
      old New Zealand white rabbits were randomized into four groups: control diet and
      room air (CA, N = 17), control diet and > or = 95% O2 (CH, N = 17), malnutrition
      and room air (MA, N = 18), and malnutrition and > or = 95% O2 (MH, N = 18).
      Malnutrition was defined as a 30% reduction of all the nutrients provided in the
      control diet. Treatments were maintained for 7 days, after which histological and
      morphometric analyses were conducted. Lung slices were stained with hematoxylin
      eosin, modified orcein-resorcin or picrosirius. The results of morphometric
      analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 +/
      0.19; CH: 0.96 +/- 0.28; MA: 0.65 +/- 0.17; MH: 0.79 +/- 0.22 g) and water
      content, as well as the number of alveoli (CA: 12.43 +/- 3.07; CH: 8.85 +/- 1.46;
      MA: 7.33 +/- 0.88; MH: 6.36 +/- 1.53 x 10-3/mm) and elastic and collagen fibers.
      Hyperoxia reduced the number of alveoli and increased septal thickening and the
      mean linear intercept. The reduction of alveolar number, collagen and elastic
      fibers was intensified when malnutrition and hyperoxia were associated. These
      data suggest that dietary restriction enhances the magnitude of hyperoxia-induced
      alveolar growth arrest and lung parenchymal remodeling. It is interesting to
      consider the important influence of postnatal nutrition upon lung development and
      bronchopulmonary dysplasia.

PMID- 19578642
TI  - Human papillomavirus infection and its association with cervical dysplasia in
      Ecuadorian women attending a private cancer screening clinic.
AB  - Women living in Latin American countries bear a disproportionate burden of
      cervical cancer, a condition caused by infection with the human papillomavirus
      (HPV). We performed a study in Santa Elena, Guayas (currently Santa Elena
      Province), Ecuador, to determine how often HPV could be detected in women
      attending a private cancer screening clinic. Participants underwent a Pap test,
      and vaginal and cervical swabs were performed for HPV testing by the polymerase
      chain reaction (PCR). Each participant completed a verbally administered survey.
      The mean age of 302 participants was 37.7 years (range 18 to 78 years). The
      majority of cervical and vaginal specimens contained sufficient DNA to perform
      PCR. Overall, 24.2% of the participants had either a cervical or vaginal swab
      that tested positive for HPV. In general, there was a good correlation between
      the HPV types detected in the cervical and vaginal swabs from the participants,
      but vaginal swabs were more likely to contain HPV DNA than were cervical swabs.
      The high-risk HPV types 16, 52, 58, and 59 and the low-risk HPV types 62, 71, 72,
      and 83 were the most frequently detected HPV types. The number of lifetime sexual
      partners was positively associated with detection of any HPV type, detection of
      oncogenic HPV, and abnormal Pap smears. Further studies are needed to determine
      if these results are representative of all Ecuadorian women and to determine if
      cervical cancers in Ecuadorian women are caused by the same HPV types found in
      the swab specimens obtained in this study.

PMID- 19578641
TI  - Effect of melatonin and time of administration on irradiation-induced damage to
      rat testes.
AB  - The effect of ionizing irradiation on testes and the protective effects of
      melatonin were investigated by immunohistochemical and electron microscopic
      methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats
      in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy,
      either to the total body or abdominopelvic region using a 60Co source at a focus
      of 80 cm away from the skin in the morning or evening together with vehicle (20%
      ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20
      mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity
      was increased in the irradiated group compared to control (P < 0.05). Melatonin
      treated groups showed less apoptosis as indicated by a considerable decrease in
      caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed
      that all spermatogenic cells, especially primary spermatocytes, displayed
      prominent degeneration in the groups submitted to total body and abdominopelvic
      irradiation. However, melatonin administration considerably inhibited these
      degenerative changes, especially in rats who received abdominopelvic irradiation.
      Total body and abdominopelvic irradiation induced identical apoptosis and
      testicular damage. Chronobiological assessment revealed that biologic rhythm does
      not alter the inductive effect of irradiation. These data indicate that melatonin
      protects against total body and abdominopelvic irradiation. Melatonin was more
      effective in the evening abdominopelvic irradiation and melatonin-treated group
      than in the total body irradiation and melatonin-treated group.

PMID- 19578643
TI  - A novel polar-based human face recognition computational model.
AB  - Motivated by a recently proposed biologically inspired face recognition approach,
      we investigated the relation between human behavior and a computational model
      based on Fourier-Bessel (FB) spatial patterns. We measured human recognition
      performance of FB filtered face images using an 8-alternative forced-choice
      method. Test stimuli were generated by converting the images from the spatial to
      the FB domain, filtering the resulting coefficients with a band-pass filter, and
      finally taking the inverse FB transformation of the filtered coefficients. The
      performance of the computational models was tested using a simulation of the
      psychophysical experiment. In the FB model, face images were first filtered by
      simulated V1- type neurons and later analyzed globally for their content of FB
      components. In general, there was a higher human contrast sensitivity to radially
      than to angularly filtered images, but both functions peaked at the 11.3-16
      frequency interval. The FB-based model presented similar behavior with regard to
      peak position and relative sensitivity, but had a wider frequency band width and
      a narrower response range. The response pattern of two alternative models, based
      on local FB analysis and on raw luminance, strongly diverged from the human
      behavior patterns. These results suggest that human performance can be
      constrained by the type of information conveyed by polar patterns, and
      consequently that humans might use FB-like spatial patterns in face processing.

PMID- 19578644
TI  - How auditory temporal processing deficits relate to dyslexia.
AB  - Studies have shown that dyslexic children present a deficiency in the temporal
      processing of auditory stimuli applied in rapid succession. However, discussion
      continues concerning the way this deficiency can be influenced by temporal
      variables of auditory processing tests. Therefore, the purpose of the present
      study was to analyze by auditory temporal processing tests the effect of temporal
      variables such as interstimulus intervals, stimulus duration and type of task on
      dyslexic children compared to a control group. Of the 60 children evaluated, 33
      were dyslexic (mean age = 10.5 years) and 27 were normal controls (mean age =
      10.8 years). Auditory processing tests assess the abilities of discrimination and
      ordering of stimuli in relation to their duration and frequency. Results showed a
      significant difference in the average accuracy of control and dyslexic groups
      considering each variable (interstimulus intervals: 47.9 +/- 5.5 vs 37.18 +/-
      6.0; stimulus duration: 61.4 +/- 7.6 vs 50.9 +/- 9.0; type of task: 59.9 +/- 7.9
      vs 46.5 +/- 9.0) and the dyslexic group demonstrated significantly lower
      performance in all situations. Moreover, there was an interactive effect between
      the group and the duration of stimulus variables for the frequency-pattern tests,
      with the dyslexic group demonstrating significantly lower results for short
      durations (53.4 +/- 8.2 vs 48.4 +/- 11.1), as opposed to no difference in
      performance for the control group (62.2 +/- 7.1 vs 60.6 +/- 7.9). These results
      support the hypothesis that associates dyslexia with auditory temporal
      processing, identifying the stimulus-duration variable as the only one that
      unequally influenced the performance of the two groups.

PMID- 19578645
TI  - Antinociceptive effects of the essential oil of Mentha x villosa leaf and its
      major constituent piperitenone oxide in mice.
AB  - Mentha x villosa Huds (Labiatae) is an aromatic herb widely used in folk
      medicine. Since the essential oil of the herb has many pharmacological
      activities, including antispasmodic effects, we determined whether the oil and
      its major constituent, piperitenone oxide (PO), have antinociceptive activity.
      The essential oil of M. x villosa (EOMV) and PO administered orally at 200 mg/kg
      (vehicle: 0.1% Tween 80 in water) significantly reduced the writhings induced by
      acetic acid from control values of 59.5 +/- 3.1 s (N = 10) to 31.9 +/- 2.8 s (N =
      10) and 23.8 +/- 3.4 s (N = 10), respectively. When administered at 100 and 200
      mg/kg, EOMV reduced the paw licking time for the second phase of the formalin
      test from the control value of 20.6 +/- 2.1 s (N = 13) to 5.3 +/- 2.2 s (N = 12)
      and 2.7 +/- 1.2 s (N = 18), respectively. At 100 and 200 mg/kg, PO reduced this
      second phase to 8.3 +/- 2.7 s (N = 12) and 3.0 +/- 1.2 s (N = 10), respectively.
      This effect of EOMV and PO was not reversed by naloxone. EOMV and PO had no
      significant effect on the first phase of the formalin test. As evaluated by the
      hot-plate and tail immersion test, EOMV and PO, at doses up to 200 mg/kg, showed
      no analgesic activity. These results show that EOMV and PO have antinociceptive
      activity and suggest that this effect is probably an indirect anti-inflammatory
      effect, which does not involve the central nervous system.

PMID- 19578646
TI  - The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment
      outcome in rheumatoid arthritis.
AB  - Despite the availability of several new agents for the treatment of rheumatoid
      arthritis (RA), sulfasalazine remains the mainstay because of both cost and
      experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved
      in folate metabolism and several polymorphisms have been described in the MTHFR
      gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with
      altered enzyme activity. To examine the association between 677C>T and 1298A>C
      MTHFR polymorphisms and sulfasalazine efficacy for the treatment of RA, a total
      of 117 RA patients treated with sulfasalazine (1 g daily; duration of treatment
      17 +/- 5 months) were analyzed. The 677C>T and 1298 A>C polymorphisms were
      detected using a PCR-RFLP method. RA was diagnosed according to the criteria of
      the American College of Rheumatology (ACR). The remission of RA symptoms was
      evaluated according to the ACR 20% response criteria. Allele and genotype
      frequencies were compared by the two-sided Fisher exact test. The frequency of
      remission was 47.2% and 44.6% in carriers of 677T and 1298C alleles, compared to
      40.7% and 42.0% in carriers of 677C and 1298A alleles, respectively. These
      differences were statistically non-significant. When the multivariate analysis
      was additionally adjusted for patients' age, gender and RA duration, the
      association of the MTHFR 677T allele with increased frequency of remission was
      statistically significant. Although RA remission rate in carriers of the MTHFR
      677T and 1298C alleles was more frequently observed, it does not seem that 677C>T
      and 1298A>C MTHFR polymorphisms have a major influence on treatment outcome in RA
      patients treated with sulfasalazine.

PMID- 19578647
TI  - Estimation procedures affect the center of pressure frequency analysis.
AB  - Even though frequency analysis of body sway is widely applied in clinical
      studies, the lack of standardized procedures concerning power spectrum estimation
      may provide unreliable descriptors. Stabilometric tests were applied to 35
      subjects (20-51 years, 54-95 kg, 1.6-1.9 m) and the power spectral density
      function was estimated for the anterior-posterior center of pressure time series.
      The median frequency was compared between power spectra estimated according to
      signal partitioning, sampling rate, test duration, and detrending methods. The
      median frequency reliability for different test durations was assessed using the
      intraclass correlation coefficient. When increasing number of segments,
      shortening test duration or applying linear detrending, the median frequency
      values increased significantly up to 137%. Even the shortest test duration
      provided reliable estimates as observed with the intraclass coefficient (0.74
      0.89 confidence interval for a single 20-s test). Clinical assessment of balance
      may benefit from a standardized protocol for center of pressure spectral analysis
      that provides an adequate relationship between resolution and variance. An
      algorithm to estimate center of pressure power density spectrum is also proposed.

PMID- 19578648
TI  - Method for automatic detection of wheezing in lung sounds.
AB  - The present report describes the development of a technique for automatic
      wheezing recognition in digitally recorded lung sounds. This method is based on
      the extraction and processing of spectral information from the respiratory cycle
      and the use of these data for user feedback and automatic recognition. The
      respiratory cycle is first pre-processed, in order to normalize its spectral
      information, and its spectrogram is then computed. After this procedure, the
      spectrogram image is processed by a two-dimensional convolution filter and a half
      threshold in order to increase the contrast and isolate its highest amplitude
      components, respectively. Thus, in order to generate more compressed data to
      automatic recognition, the spectral projection from the processed spectrogram is
      computed and stored as an array. The higher magnitude values of the array and its
      respective spectral values are then located and used as inputs to a multi-layer
      perceptron artificial neural network, which results an automatic indication about
      the presence of wheezes. For validation of the methodology, lung sounds recorded
      from three different repositories were used. The results show that the proposed
      technique achieves 84.82% accuracy in the detection of wheezing for an isolated
      respiratory cycle and 92.86% accuracy for the detection of wheezes when detection
      is carried out using groups of respiratory cycles obtained from the same person.
      Also, the system presents the original recorded sound and the post-processed
      spectrogram image for the user to draw his own conclusions from the data.

PMID- 19578649
TI  - Endogenous angiotensin II modulates nNOS expression in renovascular hypertension.
AB  - Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal
      nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is
      modulated by endogenous angiotensin II, an inhibitor of NO function. We tested
      the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated
      by NADPH oxidase contribute to the modulation of renal nNOS expression in two
      kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male
      Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham
      operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N
      = 9) was compared by Western blotting to that of 2K1C rats treated with low doses
      of the AT1 antagonist losartan [10 mg x kg(-1) x day(-1); N = 5] or the
      superoxide scavenger tempol [0.2 mmol x kg(-1) x day(-1); N = 5], which still
      remain hypertensive. After 28 days, nNOS expression was significantly increased
      by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped
      kidneys of 2K1C rats compared with sham rats, but was normalized by losartan.
      With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys
      and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in
      nNOS expression were not followed by changes in the enzyme activity, as measured
      indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress
      seem to be primary stimuli for increased nNOS expression, but this up-regulation
      does not result in higher enzyme activity.

PMID- 19578651
TI  - Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose for initial
      staging of hodgkin lymphoma: a single center experience in Brazil.
AB  - BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET) is a well established
      functional imaging modality for the initial staging of Hodgkin lymphoma (HL) in
      patients from Western Europe and North America. The reliability of FDG-PET in
      populations of different ethnic groups is unclear, as all investigations
      published to date have come from developed countries. PURPOSE: The aim of the
      present study was to investigate the effectiveness of FDG-PET in the initial
      staging of HL patients in a Brazilian population. METHODS: Eighty-two patients
      with newly diagnosed HL were prospectively included in the study. All patients
      were staged with both conventional clinical staging (CCS) methods, including
      computed tomography (CT) and whole-body FDG-PET methods. A standard of reference
      for the nodal regions and the extranodal organs was determined using all
      available information, including the CCS methods, FDG-PET, the diagnostic
      histology and the follow-up examinations. The results of the CCS were then
      compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher
      for nodal staging than that of CT (87.8% vs. 61.6%, respectively). FDG-PET was
      also more sensitive than CT in regard to evaluating the extranodal organs for
      lymphomatous involvement (96.2% vs. 40.0%, respectively). FDG-PET detected all 16
      patients who were characterized by a positive bone marrow biopsy and identified
      an additional 4 patients with bone marrow disease. The incorporation of FDG-PET
      coupled with CCS in the staging procedure upstaged 20% (17/82) of the patients
      and downstaged 11% (9/82) of the patients. As a result of these changes in
      staging, 15% (13/82) of the patients would have received a different therapeutic
      regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of
      nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the
      disease was the most common result (20% of patients) brought about by the
      addition of PET to the staging algorithm, even in a population of patients with a
      high incidence of advanced disease. However, changes in stages based on FDG-PET
      results should be confirmed by biopsy.

PMID- 19578652
TI  - Endobronchial ultrasound application for diagnosis of tracheobronchial tree
      invasion by esophageal cancer.
AB  - INTRODUCTION: Esophageal cancer staging has been performed through bronchoscopy,
      computerized tomography (CT), positron emission tomography (PET), and endoscopic
      ultrasound (EUS). Whereas CT and PET scan provide assessments of distant
      metastasis, bronchoscopy importantly diagnoses tracheobronchial involvement,
      complementing chest CT findings. EUS is the most accurate examination for T and N
      staging but is technically limited when tumoral stenoses cannot be traversed.
      Endobronchial ultrasound (EBUS) appears to present greater accuracy than EUS, CT,
      and bronchoscopy for assessing tracheobronchial wall involvement. EBUS has been
      recently associated with EUS for esophageal cancer staging in our unit.
      OBJECTIVE: To compare EBUS findings in esophageal cancer patients without evident
      signs of tracheobronchial invasion on conventional bronchoscopy with EUS and CT.
      METHODS: Fourteen patients with esophageal cancer underwent CT, conventional
      bronchoscopy, EUS, and EBUS for preoperative staging. All patients underwent EBUS
      and EUS with an Olympus(R) MH-908 echoendoscope at 7.5 MHz. Seven patients were
      eligible for the study according to the inclusion criteria. RESULTS: The
      echoendoscope could not traverse tumoral esophageal stenosis to perform EUS in
      two patients, and invasion was effectively diagnosed by EBUS. In 4 (57%) of 7
      patients EBUS revealed additional information to staging. In the remaining 3
      cases the invasion findings were the same under both EUS and EBUS. CONCLUSION:
      EBUS showed signs of tracheobronchial invasion not observed by conventional
      bronchoscopy, adding information to staging in most of the cases when compared
      with CT and EUS.

PMID- 19578653
TI  - Effects of isoflavones on the skin of postmenopausal women: a pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of isoflavones on
      the skin of postmenopausal women. DESIGN: A prospective study was performed with
      30 postmenopausal women before and immediately after the end of treatment with
      100 mg/day of an isoflavones-rich, concentrated soy extract for six months. A
      skin punch was performed in the gluteal region for sample collection before and
      immediately after the treatment program. Morphometric determination of epidermal
      thickness, the papillary index (wrinkling), and the amount of dermal elastic and
      collagen fibers was assessed. In addition, the number of blood vessels in the
      sample was also evaluated. The paired Student's t-test was used for statistical
      analysis (P < 0.05). RESULTS: Isoflavone treatment resulted in a 9.46% increase
      in the thickness of the epidermis in 23 patients. In addition, the papillary
      index was reduced in 21 women. The papillary index was inversely proportional to
      skin wrinkling, i.e., there were a large number of papillae after treatment. The
      amount of collagen in the dermis was increased in 25 women (86.2%). In 22 women
      (75.8%) we observed that the number of elastic fibers increased. The number of
      dermal blood vessels was significantly increased in 21 women. CONCLUSION: Our
      data show that the use of a concentrated, isoflavone-rich soy extract during six
      consecutive months caused significant increases in epithelial thickness, the
      number of elastic and collagen fibers, as well as the blood vessels.

PMID- 19578654
TI  - Sequential allocation to balance prognostic factors in a psychiatric clinical
      trial.
AB  - OBJECTIVE: This paper aims to describe and discuss a minimization procedure
      specifically designed for a clinical trial that evaluates treatment efficacy for
      OCD patients. METHOD: Aitchison's compositional distance was used to calculate
      vectors for each possibility of allocation in a covariate adaptive method. Two
      different procedures were designed to allocate patients in small blocks or
      sequentially one-by-one. RESULTS: We present partial results of this allocation
      procedure as well as simulated data. In the clinical trial for which this
      procedure was developed, successful balancing between treatment arms was
      achieved. Separately, in an exploratory analysis, we found that if the arrival
      order of patients was altered, most patients were allocated to a different
      treatment arm than their original assignment. CONCLUSION: Our results show that
      the random arrival order of patients determine different assignments and
      therefore maintains the unpredictability of the allocation method. We conclude
      that our proposed procedure allows for the use of a large number of prognostic
      factors in a given allocation decision. Our method seems adequate for the design
      of the psychiatric trials used as models. Trial registrations are available at
      clinicaltrials.gov NCT00466609 and NCT00680602.

PMID- 19578655
TI  - Spirometric assessment of lung transplant patients: one year follow-up.
AB  - OBJECTIVE: The purpose of this study was to compare spirometry data between
      patients who underwent single-lung or double-lung transplantation the first year
      after transplantation. INTRODUCTION: Lung transplantation, which was initially
      described as an experimental method in 1963, has become a therapeutic option for
      patients with advanced pulmonary diseases due to improvements in organ
      conservation, surgical technique, immunosuppressive therapy and treatment of post
      operative infections. METHODS: We retrospectively reviewed the records of the 39
      patients who received lung transplantation in our institution between August 2003
      and August 2006. Twenty-nine patients survived one year post-transplantation, and
      all of them were followed. RESULTS: The increase in lung function in the double
      lung transplant group was more substantial than that of the single-lung
      transplant group, exhibiting a statistical difference from the 1st month in both
      the forced expiratory volume in one second (FEV1) and the forced vital capacity
      (FVC) in comparison to the pre-transplant values (p <0.05). Comparison between
      double-lung transplant and single lung-transplant groups of emphysema patients
      demonstrated a significant difference in lung function beginning in the 3rd month
      after transplantation. DISCUSSION: The analyses of the whole group of transplant
      recipients and the sub-group of emphysema patients suggest the superiority of
      bilateral transplant over the unilateral alternative. Although the pre-transplant
      values of lung function were worse in the double-lung group, this difference was
      no longer significant in the subsequent months after surgery. CONCLUSION:
      Although both groups demonstrated functional improvement after transplantation,
      there was a clear tendency to greater improvement in FVC and FEV1 in the
      bilateral transplant group. Among our subjects, double-lung transplantation
      improved lung function.

PMID- 19578656
TI  - Comparison between measurements obtained with three different perineometers.
AB  - OBJECTIVE: To analyze the results obtained in the evaluation of intra-vaginal
      pressure using three different brands of perineometers in nulliparous volunteers.
      MATERIALS AND METHODS: Twenty nulliparous women with no anatomical alterations
      and/or dysfunction of the pelvic floor were enrolled in our study. All the women
      had the ability to voluntarily contract their PFM (Pelvic Floor Muscles), as
      assessed by digital palpation. The intra-vaginal pressure was assessed using
      three different brands of perineometer (Neurodyn Evolution, SensuPower and
      Peritron). Each volunteer was evaluated on three alternate days by a single
      examiner using a single brand of perineometer on each day. In the assessment, the
      volunteers were required to pull (contract) their PFM in and up as strongly as
      possible 3 times and to sustain the contraction for 5 seconds, with an interval
      of 30 seconds between each pull. For the statistical analysis, a concordance
      correlation coefficient was used to compare the values that were obtained with
      each brand of perineometer. RESULTS: A moderate concordance (0.51) was found
      between the results from the Peritron and Neurodyn perineometers, a fair
      concordance (0.21) between the Peritron and SensuPower brands and a poor
      concordance (0.19) between the Neurodyn and SensuPower brands. CONCLUSION: The
      concordance of the measurements of the intra-vaginal pressure ranged from poor to
      moderate, suggesting that perineometers of different brands generate different
      results.

PMID- 19578657
TI  - Surgical resection of lung metastases: results from 529 patients.
AB  - OBJECTIVE: The aim of this study is to determine clinical, pathological, and
      treatment-relevant variables associated with long-term (90-month) overall
      survival in patients with lung metastases undergoing pulmonary metastasectomy.
      METHODS: A retrospective review was performed of patients who were admitted with
      lung metastases, and who underwent thoracotomy for resection, after treatment of
      a primary tumor. Data were collected regarding demographics, tumor features,
      treatment, and outcome. RESULTS: Patients (n = 529) were submitted to a total of
      776 thoracotomies. Median follow-up time across all patients was 21.6 months
      (range: 0-192 months). The postoperative complication rate was 9.3%, and the 30
      day mortality rate was 0.2%. The ninety-month overall survival rate for all
      patients was 30.4%. Multivariate analysis identified the number of pulmonary
      nodules detected on preoperative CT-scan, the number of malignant nodules
      resected, and complete resection as the independent prognostic factors for
      overall survival. CONCLUSION: These results confirm that lung metastasectomy is a
      safe and potentially curative procedure for patients with treated primary tumors.
      A select group of patients can achieve long-term survival after resection.

PMID- 19578658
TI  - Long-term surgical outcomes of primary congenital glaucoma in China.
AB  - OBJECTIVE: To evaluate the long-term outcomes of three surgical procedures for
      the treatment of primary congenital glaucoma (PCG). INTRODUCTION: PCG is one of
      the main causes of blindness in children. There is a paucity of contemporary data
      on PCG in China. METHODS: A retrospective study of 48 patients (81 eyes) with PCG
      who underwent primary trabeculectomy, trabeculotomy, or combined trabeculotomy
      and trabeculectomy (CTT). RESULTS: All patients were less than 4 years (yrs) of
      age, with a mean age of 2.08 +/- 1.23 yrs. The mean duration of follow-up was
      5.49 +/- 3.09 yrs. The difference in success rates among the three surgical
      procedures at 1, 3, 6 and 9 yrs was not statistically significant (p = 0.492).
      However, in patients with over 4 yrs of follow-up, Kaplan-Meier survival analysis
      revealed that the success rates of trabeculectomy and CTT declined more slowly
      than that of trabeculotomy. Among the patients, 66.22% acquired good vision (VA >
      0.4), 17.57% acquired fair vision (VA = 0.1 - 0.3), and 16.22% acquired poor
      vision (VA < 0.1). The patients with good vision were mostly in the successful
      surgery group. Myopia was more prevalent postoperatively (p = 0.009). Reductions
      in the cup-disc ratio and corneal diameter were only seen in the successful
      surgery group (p = 0.000). In addition, the successful surgery group contained
      more patients that complied with a regular follow-up routine (p = 0.002).
      DISCUSSION: Our cases were all primary surgeries. Primary trabeculectomy was
      performed in many cases because no treatment was sought until an advanced stage
      of disease had been reached. CONCLUSIONS: In contrast to most reports, in the
      present study, trabeculectomy and CTT achieved higher long-term success rates
      than trabeculotomy. The patients with successful surgical results had better
      vision. Compliance with a routine of regular follow-up may increase the chances
      of a successful surgical outcome.

PMID- 19578659
TI  - The role of invasive therapies in elderly patients with acute myocardial
      infarction.
AB  - INTRODUCTION: In elderly patients with acute myocardial infarction, very little
      is known about the role of surgical myocardial revascularization and percutaneous
      coronary intervention (invasive therapies--IT), especially in the context of long
      term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with
      MI who had been included prospectively in a databank and followed for up to 7.5
      years. In this population, 548 patients were >70 years old (elderly group--EG),
      and 1040 were <70 years of age (younger group--YG); 1088 underwent IT during
      hospitalization, and the remaining 500 were treated medically (conservative
      therapy--CT). Patients were monitored either by visit or by phone at least once a
      year. A standard questionnaire was administered to all patients. The impact of IT
      was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of
      the follow-up period, the survival rates for the IT and CT groups were,
      respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55,
      P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8%
      versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the
      hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG
      (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of
      patients with myocardial infarction revealed that IT during the in-hospital phase
      was at least as effective in elderly patients as in younger patients.

PMID- 19578660
TI  - Radio frequency electromagnetic radiation (RF-EMR) from GSM (0.9/1.8GHz) mobile
      phones induces oxidative stress and reduces sperm motility in rats.
AB  - INTRODUCTION: Mobile phones have become indispensable in the daily lives of men
      and women around the globe. As cell phone use has become more widespread,
      concerns have mounted regarding the potentially harmful effects of RF-EMR from
      these devices. OBJECTIVE: The present study was designed to evaluate the effects
      of RF-EMR from mobile phones on free radical metabolism and sperm quality.
      MATERIALS AND METHODS: Male albino Wistar rats (10-12 weeks old) were exposed to
      RF-EMR from an active GSM (0.9/1.8 GHz) mobile phone for 1 hour continuously per
      day for 28 days. Controls were exposed to a mobile phone without a battery for
      the same period. The phone was kept in a cage with a wooden bottom in order to
      address concerns that the effects of exposure to the phone could be due to heat
      emitted by the phone rather than to RF-EMR alone. Animals were sacrificed 24
      hours after the last exposure and tissues of interest were harvested. RESULTS:
      One hour of exposure to the phone did not significantly change facial temperature
      in either group of rats. No significant difference was observed in total sperm
      count between controls and RF-EMR exposed groups. However, rats exposed to RF-EMR
      exhibited a significantly reduced percentage of motile sperm. Moreover, RF-EMR
      exposure resulted in a significant increase in lipid peroxidation and low GSH
      content in the testis and epididymis. CONCLUSION: Given the results of the
      present study, we speculate that RF-EMR from mobile phones negatively affects
      semen quality and may impair male fertility.

PMID- 19578661
TI  - Effects of the histamine H2 receptor antagonist famotidine on the healing of
      colonic anastomosis in rats.
AB  - BACKGROUND: Failure of anastomotic healing is one of the major complications in
      colorectal surgery. Because histamine plays an important role in immune and
      inflammatory reactions, we demonstrate the effects of famotidine on the healing
      of colonic anastomosis in rats. METHODS: Twenty-eight Sprague-Dawley rats were
      used in the study. Excision and end-to-end anastomosis was performed in the
      distal colon of the rat. The Famotidine Group received 2 mg/kg/day famotidine;
      the Control Group received the same amount of saline. Bursting pressure of
      anastomoses and hydroxyproline content of perianastomotic tissues were evaluated
      on the third and seventh days following surgery. RESULTS: Bursting pressures and
      hydroxyproline contents for the Famotidine Group were significantly lower than
      the equivalent parameters for the Control Group on both the third and seventh
      days post-surgery. CONCLUSIONS: According to our findings, famotidine exerts
      detrimental effects on the anastomotic bursting pressure and hydroxyproline
      content of perianastomotic tissues in the colon of rats.

PMID- 19578662
TI  - Assessing the scientific research productivity of a Brazilian healthcare
      institution: a case study at the Heart Institute of Sao Paulo, Brazil.
AB  - INTRODUCTION: The present study was motivated by the need to systematically
      assess the research productivity of the Heart Institute (InCor), Medical School
      of the University of Sao Paulo, Brazil. OBJECTIVE: To explore methodology for the
      assessment of institutional scientific research productivity. MATERIALS AND
      METHODS: Bibliometric indicators based on searches for author affiliation of
      original scientific articles or reviews published in journals indexed in the
      databases Web of Science, MEDLINE, EMBASE, LILACS and SciELO from January 2000 to
      December 2003 were used in this study. The retrieved records were analyzed
      according to the index parameters of the journals and modes of access. The number
      of citations was used to calculate the institutional impact factor. RESULTS: Out
      of 1253 records retrieved from the five databases, 604 original articles and
      reviews were analyzed; of these, 246 (41%) articles were published in national
      journals and 221 (90%) of those were in journals with free online access through
      SciELO or their own websites. Of the 358 articles published in international
      journals, 333 (93%) had controlled online access and 223 (67%) were available
      through the Capes Portal of Journals. The average impact of each article for
      InCor was 2.224 in the period studied. CONCLUSION: A simple and practical
      methodology to evaluate the scientific production of health research institutions
      includes searches in the LILACS database for national journals and in MEDLINE and
      the Web of Science for international journals. The institutional impact factor of
      articles indexed in the Web of Science may serve as a measure by which to assess
      and review the scientific productivity of a research institution.

PMID- 19578663
TI  - Histomorphometric analysis of cutaneous remodeling in the early stage of the
      scleroderma model.
AB  - INTRODUCTION/OBJECTIVES: Systemic sclerosis, or scleroderma, is a rheumatic
      disease characterized by autoimmunity, vasculopathy, and fibrosis of the skin and
      several internal organs. In the present study, our aim was to assess the skin
      alterations in animals with scleroderma during the first stages of disease
      induction. METHODS: To induce scleroderma, female New Zealand rabbits (n = 12)
      were subcutaneously immunized with 1 mg/ml of collagen V (Col V) in complete
      Freund's adjuvant, twice with a thirty-day interval. Fifteen days later, the
      animals received an intramuscular booster with type V collagen in incomplete
      Freund's adjuvant, twice with a fifteen-day interval. The control group was
      inoculated with 1 ml of 10 mM acetic acid solution diluted with an equal amount
      of Freund's adjuvant. Serial dorsal skin biopsies were performed at 7, 15, and 30
      days and stained with H&E, Masson's trichrome and Picrosirius for morphological
      and morphometric analyses. RESULTS: Immunized rabbits presented a significant
      increase in collagen in skin collected seven days after the first immunization
      (p=0.05). CONCLUSION: The results from this experimental model may be very
      important to a better understanding of the pathogenic mechanisms involved in the
      beginning of human SSc. Therapeutic protocols to avoid early remodeling of the
      skin may lead to promising treatments for SSc in the future.

PMID- 19578664
TI  - Evaluating humidity recovery efficiency of currently available heat and moisture
      exchangers: a respiratory system model study.
AB  - OBJECTIVES: To evaluate and compare the efficiency of humidification in available
      heat and moisture exchanger models under conditions of varying tidal volume,
      respiratory rate, and flow rate. INTRODUCTION: Inspired gases are routinely
      preconditioned by heat and moisture exchangers to provide a heat and water
      content similar to that provided normally by the nose and upper airways. The
      absolute humidity of air retrieved from and returned to the ventilated patient is
      an important measurable outcome of the heat and moisture exchangers' humidifying
      performance. METHODS: Eight different heat and moisture exchangers were studied
      using a respiratory system analog. The system included a heated chamber (acrylic
      glass, maintained at 37 degrees C), a preserved swine lung, a hygrometer,
      circuitry and a ventilator. Humidity and temperature levels were measured using
      eight distinct interposed heat and moisture exchangers given different tidal
      volumes, respiratory frequencies and flow-rate conditions. Recovery of absolute
      humidity (%RAH) was calculated for each setting. RESULTS: Increasing tidal
      volumes led to a reduction in %RAH for all heat and moisture exchangers while no
      significant effect was demonstrated in the context of varying respiratory rate or
      inspiratory flow. CONCLUSIONS: Our data indicate that heat and moisture
      exchangers are more efficient when used with low tidal volume ventilation. The
      roles of flow and respiratory rate were of lesser importance, suggesting that
      their adjustment has a less significant effect on the performance of heat and
      moisture exchangers.

PMID- 19578666
TI  - Prosthesis for open pleurostomy versus open thoracic window.

PMID- 19578665
TI  - Hyperkalemia accompanies hemorrhagic shock and correlates with mortality.
AB  - OBJECTIVE: This study was designed to evaluate the effects of terlipressin versus
      fluid resuscitation with normal saline, hypertonic saline or hypertonic
      hyperoncotic hydroxyethyl starch, on hemodynamics, metabolics, blood loss and
      short-term survival in hemorrhagic shock. METHOD: Twenty-nine pigs were subjected
      to severe liver injury and treated 30 min later with either: (1) 2 mg
      terlipressin in a bolus, (2) placebo-treated controls, (3) 4 mL/kg 7.5%
      hypertonic NaCl, (4) 4 mL/kg 7.2% hypertonic-hyperoncotic hydroxyethyl starch
      200/0.5, or (5) normal saline at three times lost blood volume. RESULTS: The
      overall mortality rate was 69%. Blood loss was significantly higher in the
      hypertonic-hyperoncotic hydroxyethyl starch and normal saline groups than in the
      terlipressin, hypertonic NaCl and placebo-treated controls groups (p<0.005).
      Hyperkalemia (K>5 mmol/L) before any treatment occurred in 66% of the patients
      (80% among non-survivors vs. 22% among survivors, p=0.019). Post-resuscitation
      hyperkalemia occurred in 86.66% of non-survivors vs. 0% of survivors (p<0.001).
      Hyperkalemia was the first sign of an unsuccessful outcome for the usual
      resuscitative procedure and was not related to arterial acidemia. Successfully
      resuscitated animals showed a significant decrease in serum potassium levels
      relative to the baseline value. CONCLUSION: Hyperkalemia accompanies hemorrhagic
      shock and, in addition to providing an early sign of the acute ischemic insult
      severity, may be responsible for cardiac arrest related to hemorrhagic shock.

PMID- 19578668
TI  - Isolated primary breast tuberculosis: report of three cases and review of the
      literature.

PMID- 19578669
TI  - [Current situation and new perspectives on the early diagnosis of ovarian
      cancer].

PMID- 19578670
TI  - [Amniotic fluid volume associated with fetal anomalies diagnosed in a reference
      center in the Brazilian Northeast].
AB  - PURPOSE: to determine factors associated to amniotic fluid volume and frequencies
      of fetal anomalies, in a reference center in Pernambuco. METHODS: a transversal
      study performed in high-risk pregnant women submitted to obstetrical
      morphological ultrasound, from March 2002 to March 2006, at an institution from
      Recife, Pernambuco, Brasil. The intrauterine diagnosis was confirmed after birth.
      Sociodemographic and obstetrical characteristics, amniotic liquid volume and
      presence of fetal anomalies were the variables studied. Fisher's exact, chi2, and
      Student's t tests, at a significance level of 5% were applied to verify the
      correlation among the variables. Prevalence rate and confidence interval at 95%
      were calculated. Multiple logistic regression analysis was performed at a
      significance level of 5%. RESULTS: Two hundred and fifty-seven pregnant women
      (56.2%) with congenital anomalies and 200 (43.8%) without anomalies, confirmed in
      the postnatal, were included in the study. The average of maternal ages and
      gestation periods were 24.8+/-6.5 years and 35.9+/-3.7 weeks, respectively. The
      fetal anomalies were discovered in the central nervous system (50.6%) and
      genitourinary tract (23.0%). The presence of congenital anomalies were
      significantly linked with reduced liquid/oligohydramnios (p=0.0002) and increased
      liquid/polyhydramnios (p<0.0001). Intrauterine mortality was more frequent in the
      group with anomalies, as compared to the healthy fetuses (10.5 versus 2.5%;
      p<0.01). CONCLUSIONS: The rate of congenital anomalies in the high-risk pregnant
      women group was 56.2%. Most of the central nervous system malformations were
      diagnosed intrauterus. Changes in the amniotic fluid were the factors more
      strongly associated with congenital anomalies.

PMID- 19578667
TI  - Mammary and extramammary Paget's disease: a study of 14 cases and the associated
      therapeutic difficulties.

PMID- 19578671
TI  - [Geoprocessing to identify the pattern of birth profile in Vale do Paraiba].
AB  - PURPOSE: to apply geoprocessing techniques for the spatial birth profile analysis
      of each municipality. METHODS: ecological and exploratory study, using data from
      the Health Information System about born alive babies in 2004, and using
      geoprocessing techniques. The spatial autocorrelations of the variables: cesarean
      section, mother's schooling, low birth weight, Apgar score at five minutes,
      prematurity, number of medical appointments and adolescent mothers, besides the
      map with the index of human development were estimated. For the detection of
      spatial events aggregates, Moran's I M statistics, through the program Terra View
      3.13 (developed by INPE and available to the public) was used. Spatial maps with
      those variables were built, and Pearson's correlation coefficients, estimated.
      RESULTS: results have shown that the rate of born alive babies, from mothers with
      school level over primary school and from cesarean sections, presented a spatial
      pattern visually identifiable and significant spatial self-correlation. Low birth
      weight, prematurity, Apgar score, number of pre-natal appointments and adolescent
      mothers have presented a random spatial pattern, showing that, in this analysis
      scale, those markers have not discriminated the risk groups, despite their
      unquestionable predictive value for children's morbidity-mortality at individual
      level. There has been a positive correlation between cesarean section and
      schooling, and between cesarean section and human development index; and a
      negative correlation between adolescent mothers and human development index, with
      statistical significance (p<0.05). CONCLUSIONS: this methodology has allowed us
      to identify spatial clusters for the variables cesarean section and mother's
      schooling, besides deepening our knowledge on birth profile in the
      municipalities, presenting good potential on how to direct actions for specific
      areas.

PMID- 19578672
TI  - [Phenotypic characterization of yeasts isolated from the vaginal mucosa of adult
      women].
AB  - PURPOSE: to characterize, phenotypically, yeasts isolated from the vaginal
      content of 223 symptomatic (S) and asymptomatic (A) adult women with
      vulvovaginitis, and to determine the clinical indicators which may lead to the
      appearance of signs and symptoms related to the mucosa involvement by this
      pathology. METHODS: a questionnaire with open and closed questions on
      epidemiological clinical data was applied initially. Then, mycological diagnosis
      with sowing in Chrom Agar Candida was done, followed by micro-morphological and
      biochemical identification. Specific methods for the detection of the virulence
      factors, proteinase and phospholipase were employed. Statistical analysis was
      performed through chi2 and Pearson's chi2 tests. RESULTS: the most prevalent
      species found was Candida albicans (87%, S and 67%, A) followed by Candida
      glabrata (4%, S e 17% A). The number of women reporting the use of contraceptives
      was higher among the symptomatic, 77%. In the two groups studied, about 87% of
      the women presented regular menstrual cycles and 57% were married with ages
      between 30 to 40 years old. Concerning the sexual practices, there has been
      concomitance among anal, oral and vaginal habits from the patients. Only Candida
      albicans produced the virulence factor phospholipase in 37.5% of them. Proteinase
      has been detected in Candida albicans, Candida glabrata and Candida parapsilosis.
      This latter virulence factor was mainly associated to isolates from symptomatic
      patients. CONCLUSIONS: it is a fact that the vaginal mucosa can be colonized and
      infected by yeasts, with several Candida species present. Nevertheless, Candida
      albicans is the most prevalent in the vaginal mucosa of adult women. It is
      evident the emergence of non-albicans Candida species, some of them with
      intrinsic resistance to azolics, such as Candida glabrata, Candida parapsilosis,
      Candida tropicalis, and Candida guillermondii, which can be explained by the
      inadequate use of medicines and empirical treatment.

PMID- 19578673
TI  - [Obesity as a risk factor to Burch surgery failure].
AB  - PURPOSE: to observe the impact of obesity and other risk factors on the rate of
      failure in patients submitted to Burch's surgery for the treatment of urinary
      incontinence. METHODS: cases study of patients submitted to Burch's surgery, from
      1992 to 2003. Patients were evaluated at the second post-surgery appointment
      (average 66 days) and after one-year follow-up, and classified in two groups:
      Continent and Non-continent. Variables analyzed were: age, parity, body mass
      index (BMI), menopause duration, duration of hormonal therapy, urodynamic
      evaluation, history of urinary tract infection, previous urinary incontinence
      surgery, diabetes, cystocele and uterine prolapse, time spent in hospital,
      necessity of self-probing, post-surgical spontaneous micturition, and surgical
      wound. Data were analyzed with the Statistical Package for Social Sciences 14.0
      statistical package. For the comparison of continuous variables, Student's t-test
      or Mann-Whitney test were used, and Fisher exact and chi2 tests, for the
      categorical variables (p<0.05). RESULTS: at the second post-surgical evaluation,
      there was no significant difference between the two groups, concerning the
      variables analyzed. After one-year follow-up, from a total of 97 patients, 81
      were continent and 16, non-continent, BMI and height being different between the
      groups. In the continent group, average BMI was 27.1 and height, 1.57 m, and,
      among the non-continent, 30.8 (p=0.02) and 1.52 m (p=0.01). The BMI>30 Odds Ratio
      was 3.7 (CI95%=1.2-11.5). CONCLUSIONS: obesity has shown to be an important risk
      factor for the surgery failure in the first follow-up year. Results show that
      patients with BMI>30 have 3.7 times more chance of being non-continent one-year
      after Burch's surgery than non-obese patients.

PMID- 19578674
TI  - [Prevalence and characterization of vaginal lactobacillus species in women at
      reproductive age without vulvovaginitis].
AB  - PURPOSE: to identify species of lactobacillus isolated from the vaginal contents
      of healthy and asymptomatic women, determining the most prevalent species and
      characterizing them phenotypically. METHODS: lactobacillus have been isolated in
      selective milieu from samples of the vaginal contents of 135 women without
      complaints of vaginal secretion, and with negative laboratorial diagnosis of
      vaginal infection, followed up at an outpatient clinic. After being identified by
      multiplex PCR, the isolates have been submitted to RNAr 16S gene sequencing, when
      necessary. They have also been evaluated concerning the production of lactic
      acid, H2O2, bacteriocins and the ability to adhere to epithelial cells. RESULTS:
      eight-three lactobacillus strains were isolated and identified, L. crispatus
      (30.1%), L. jensenii (26.5%), L. gasseri (22.9%) e L. vaginalis (8.4%), being the
      prevalent species. Only 20 of those isolates did not present H2O2 production, in
      detectable amounts. From the 37 strains selected for the test of adhesion to the
      epithelial cells, 12 presented 50 to 69% of adhesion, 10 presented 70% or more,
      and the remaining, little or no adhesion at all. None of the tested strains
      produced bacteriocins. CONCLUSIONS: the lactobacillus species more prevalent in
      women without vulvovaginitis, isolated in selective culture milieu and identified
      by molecular methods were L. crispatus, L. jensenii and L. gasseri. Besides the
      fact of being more prevalent, these strains also presented better production of
      H2O2, and reached lower pH values in the culture milieu.

PMID- 19578675
TI  - [Quality of life in postmenopausal women, users and non-users of hormone
      therapy].
AB  - PURPOSE: to evaluate the quality of life of post-menopause women, users and non
      users of hormonal therapy (HT), in a Healthcare Unit in Franca, Sao Paulo,
      Brazil. METHODS: a clinical transversal study, carried out with 250 post
      menopausal women, with ages from 45 to 70 years old, attended to in Healthcare
      Units, from September 2007 to August 2008. Participants were divided into two
      groups: HT users (n=70) and non-users (n=180). Women making continuous HT use for
      at least six months were considered as users. Sociodemographic and clinical
      characteristics have been evaluated. Blatt-Kupperman's menopausal index has been
      applied to assess climacteric symptoms, and the Women's Health Questionnaire
      (WHQ), to assess their quality of life. Fisher's exact test or chi2 and Mann
      Whitney and Kruskal-Wallis's tests have been used for the statistical analysis.
      RESULTS: no significant difference has been found in the comparison of groups,
      concerning age, menarche, menopause, parity and body mass index. It has been seen
      that 67.2% of the women were married, 83.2% had attended primary school and 53.2%
      were housewives, with no difference between the groups. HT users reported lower
      frequency of climacteric symptoms (BKMI) with moderate and marked intensity, as
      compared to non-users (p<0.001). Even though HT users presented lower average
      score in cognitive deficit (p<0.001), vasomotor symptoms (p=0.04), sleeping
      problems (p<0.001), attractiveness (p=0.02) from the WHQ, there has been no
      difference in the total score, as compared to non-users. CONCLUSIONS: post
      menopausal women, HT users and non-users, admitted at Healthcare Units, have not
      presented differences in global quality of life.

PMID- 19578676
TI  - [Risk predictors for preterm birth].
AB  - Among the clinical factors for preterm birth, some confer substantial increased
      risk, including a history of preterm birth, multiple gestation and vaginal
      bleeding in the second trimester. However, these factors are present only in a
      minority of women who ultimately deliver preterm and thus have low sensitivity.
      Cervical dilatation, effacement and position as determined by manual examination
      have been related to an increased risk of preterm birth but also suffer from low
      sensitivity and positive predictive values. Cervical length measured with
      transvaginal ultrasound has also been related to an increased risk of preterm
      birth as cervical length decreases. The reported sensitivity is better than other
      tests, but positive predictive value is low. The principal utility of the fetal
      fibronectin assay lies in its negative predictive value in symptomatic women.
      Increased sensitivity has been reported when cervical length is used in
      combination with fetal fibronectin.

PMID- 19578677
TI  - [The National Science and Technology Institute in Child and Adolescence
      Developmental Psychiatry: a new paradigm for Brazilian psychiatry focused on our
      children and their future].

PMID- 19578678
TI  - Coping strategies for craving management in nicotine dependent patients.
AB  - OBJECTIVE: The aim of this study was to investigate the association between the
      intensity of craving and the types of coping skills used by nicotine-dependent
      patients. METHOD: This was an experimental study. The sample comprised 201
      subjects, mean age 38.15 years. The participants were randomly divided into
      groups of zero, 30 and 60 minutes of nicotine abstinence. The following
      instruments were administered: the Chart of Sociodemographic Data, the Fagerstrom
      Test for Nicotine Dependence, the Questionnaire of Smoking Urges, and the Coping
      Strategies Inventory. RESULTS: The most frequently used coping strategies are
      presented in descending order: accepting responsibility, self-control and
      distancing. There was a positive correlation between the confrontive coping
      strategy and the total score on the Questionnaire of Smoking Urges (rs = 0.146; p
      = 0.045) and the score on Factor 1 (rs = 0.165; p = 0.023). CONCLUSION: The most
      intense craving can lead nicotine-dependent individuals to use confrontive coping
      strategies that make them unable to control their emotions or to face the
      situations of high risk of relapse. This finding demonstrates that the treatment
      of smokers should include psychological education about the pitfalls of using
      these types of strategy and should teach them new types of coping strategies for
      craving management.

PMID- 19578679
TI  - Knowledge and attitudes related to drug abuse and prevention displayed by public
      school educators.
AB  - OBJECTIVE: To investigate the connection between knowledge about and the
      attitudes towards drug abuse by students displayed by public school educators in
      Brazil. METHOD: Cross-sectional study, with probabilistic sampling encompassing
      20% of the municipal elementary schools located in the city of Sao Paulo from
      which educators were enrolled to answer three questionnaires: 1) professional and
      personal data; 2) assessment of their attitudes in drug abuse situations; 3)
      assessment of their knowledge on drug abuse. RESULTS: Considering possible values
      between -17 and +21, professionals scored 11.5 +/- 3.8 in the Attitudes scale.
      These values correspond to more empathic attitudes. Scores in the Knowledge on
      Drugs Scale were 55.2 +/- 12.5 (possible values: 0 to 100). Correlation between
      the Attitudes Scale and the time spent working as education professionals was 
      0.288 (p < 0.01). The difference in the means in the Attitude Scale according to
      professional academic qualifications was statistically significant (-1.93, t =
      2.26; gl = 80; p < 0.05). CONCLUSION: The level of knowledge about drugs
      displayed by educators was average and not influenced by the professional's
      academic qualifications. In contrast, their attitudes were predominantly empathic
      and directly associated to their academic qualifications and inversely associated
      to the amount of time they had spent in that position.

PMID- 19578680
TI  - Seasonality of suicide in the city of Sao Paulo, Brazil, 1979-2003.
AB  - OBJECTIVE: To evaluate suicide seasonality in the city of Sao Paulo within an
      urban area and tropical zone. METHOD: Suicides were evaluated using the chi
      square test and analysis of variance (ANOVA) by comparing monthly, quarterly and
      half-yearly variations, differentiating by gender. Analyses of time series were
      carried out using the autocorrelation function and periodogram, while the
      significance level for seasonality was confirmed with the Fisher's test. RESULTS:
      The suicides of the period between 1979 and 2003 numbered 11,434 cases.
      Differences were observed in suicides occurring in Spring and Autumn for the
      total sample (ANOVA: p-value = 0.01), and in the male sample (ANOVA: p-value =
      0.02). For the analysis of time series, seasonality was significant only for the
      period of 7 months in the male sample (p-value = 0.04). DISCUSSION: In this
      study, no significant seasonal differences were observed in the occurrences of
      suicides, with the exception of the male sample. The differences observed did not
      correspond with the pattern described in studies carried out in temperate zones.
      Some of the climatic particularities of the tropical zone might explain the
      atypical pattern of seasonality of suicides found in large populations within an
      urban area and tropical zone.

PMID- 19578681
TI  - Influence of depression and early adverse experiences on illicit drug dependence:
      a case-control study.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      depression and illicit drug dependence among a Latin-American population. METHOD:
      illicit drug dependent patients (n = 137) and controls (n = 274) were interviewed
      using the Diagnostic Interview for Genetic Studies, in order to detect lifetime
      and current depressive disorder and illicit (cocaine, cannabis or inhalants)
      substance dependence. A regression analysis was used to estimate the odds ratio
      for drug dependence according to the diagnosis of depression. RESULTS: The
      lifetime diagnosis of depression (p = 0.001; OR = 4.9; 95% CI, 1.9-12.7) predicts
      illegal drugs dependence. Sociodemographic variables such as male gender (p <
      0.001; OR = 36.8; 95% CI, 11.8-114) and occupational situation (p = 0.002; OR =
      5.0; 95% CI, 1.8-13) as well as alcohol dependence (p = 0.01; OR = 3.4; 95% CI,
      1.3-8.7) significantly influenced depression and drug dependence. Additional
      influent factors detected were having parents (p = 0.006; OR = 18.9; 95% CI, 2.3
      158) or friends (p < 0.001; OR = 64.4; 95% CI, 6.5-636) who are illicit drugs
      dependents. CONCLUSION: although a causal relationship between dependence on
      illicit drugs and depression cannot be determined, comparison of the sequence of
      events point to the occurrence of depression later in life than dependence. It
      remains to be determined whether depression is a comorbidity of dependence,
      sharing etiological factors, or a consequence of drug abuse and/or abstinence.

PMID- 19578682
TI  - Bipolar disorder first episode and suicidal behavior: are there differences
      according to type of suicide attempt?
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that the
      polarity of the first mood episode may be a marker for suicidal behavior,
      particularly the violent subtype. METHOD: One hundred and sixty-eight patients
      diagnosed with bipolar disorder (DSM-IV) were grouped according to type of first
      episode: depression or manic/hypomanic. Groups were compared for demographic and
      clinical variables. We performed logistic regression in order to test the
      association between first episode polarity and suicidal behavior. RESULTS: We
      found that depressed patients have a lifetime history of more suicide attempts.
      However, univariate analysis of number of suicide attempts showed that the best
      model fits the bipolar II subtype (mean square = 15.022; p = 0.010) and lifetime
      history of psychotic episodes (mean square = 17.359; p = 0.021). Subgrouping the
      suicide attempts by subtype (violent or non-violent) revealed that
      manic/hypomanic patients had a greater tendency toward attempting violent suicide
      (21.2 vs. 14.7%, X(2) = 7.028, p = 0.03). Multiple logistic regression analysis
      confirmed this result. CONCLUSION: Depressed patients had more suicide attempts
      over time, which could be explained by the higher prevalence of bipolar II
      subtype in this group, whereas manic/hypomanic patients had a lifelong history of
      more frequent violent suicide attempts, not explained by any of the variables
      studied. Our results support the evidence that non-violent suicide attempters and
      violent suicide attempters tend to belong to different phenotypic groups.

PMID- 19578683
TI  - Health-related quality of life predictors during medical residency in a random,
      stratified sample of residents.
AB  - OBJECTIVE: To evaluate the quality of life during the first three years of
      training and identify its association with sociodemographicoccupational
      characteristics, leisure time and health habits. METHOD: A cross-sectional study
      with a random sample of 128 residents stratified by year of training was
      conducted. The Medical Outcome Study -short form 36 was administered. Mann
      Whitney tests were carried out to compare percentile distributions of the eight
      quality of life domains, according to sociodemographic variables, and a multiple
      linear regression analysis was performed, followed by a validity checking for the
      resulting models. RESULTS: The physical component presented higher quality of
      life medians than the mental component. Comparisons between the three years
      showed that in almost all domains the quality of life scores of the second year
      residents were higher than the first year residents (p < 0.01). The mental
      component scores remained high for third year residents (p < 0.01). Predictors of
      higher quality of life were: second or third year of residency, satisfaction with
      the training program, sufficient time for leisure, and care of critical patients
      for less than 30 hours per week. CONCLUSION: The mental component of quality of
      life was the most impaired component, indicating the importance of caring for
      residents' mental health, especially during their first year and when they are
      overloaded with critical patients.

PMID- 19578684
TI  - Highly reported prevalence of drinking and driving in Brazil: data from the first
      representative household study.
AB  - OBJECTIVE: Brazil lacks information about driving under the influence of alcohol
      (DUI) originated from representative samples obtained from the general
      population. METHOD: 333 subjects with a valid driver's license and drinking in
      the last 12 months were drawn from a multistaged sample of 2,346 adults from the
      first Brazilian Household Survey of Patterns of Alcohol Use. A multivariate
      analysis was conducted to understand the associations between risk factors and
      driving after drinking three or more drinks. RESULTS: the overall DUI prevalence
      reported in the sample was 34.7% - 42.5% among males and 9.2% among females.
      Being male (OR = 6.0, 95% CI 2.9-12.6), having a previous DUI accident (OR = 7.9,
      95% CI 2.5-24.9), binging in the last year (OR = 2.2, 95% CI 1.03-4.5) and having
      an unfavorable opinion towards policies (OR = 2.9, 95% CI 1.4-6.2) remained
      associated with heavy drinking and driving after model adjustments. DISCUSSION:
      This was the first study evaluating driving under the influence of alcohol in a
      representative sample of the Brazilian population. The prevalence of DUI found is
      alarming, and possibly underestimated in the sample. Results demonstrate the need
      for more studies on this association and show directions towards preventive
      strategies for the specific high-risk group of male drivers with previous
      problems with alcohol and unfavorable opinions about prevention policies.

PMID- 19578685
TI  - Association study between the -62A/T NFKBIL1 polymorphism and obsessive
      compulsive disorder.
AB  - OBJECTIVE: Evidence from family and molecular genetic studies support the
      hypothesis of involvement of immunologic mechanisms in the pathophysiology of
      obsessive-compulsive disorder. The nuclear factor of kappa light polypeptide gene
      enhancer in B-cells inhibitor-like 1 (NFKBIL1) has been suggested as a modulator
      of the immunological system. Given the importance of NFKBIL1 in the immunological
      response, the present study investigated the -62A/T polymorphism (rs2071592),
      located in the promoter region of its gene (NFKBIL1), as a genetic risk factor
      for the development of obsessive-compulsive disorder. METHOD: The -62A/T NFKBIL1
      polymorphism was investigated in a sample of 111 patients who met DSM-IV criteria
      for obsessive-compulsive disorder and 272 healthy age- and gender-matched
      controls. RESULTS: There were no differences in genotypic distributions between
      patients and controls (chi2 = 0.98; 2 d.f.; p = 0.61). DISCUSSION: Despite these
      negative findings, more comprehensive polymorphism coverage within the NFKBIL1 is
      warranted in larger samples. Populations with different ethnic backgrounds should
      also be studied. CONCLUSION: The results of the present investigation do not
      provide evidence for the association between the -62A/T NFKBIL1 polymorphism and
      obsessive-compulsive disorder in this Brazilian sample.

PMID- 19578686
TI  - Brain-derived neurotrophic factor gene val66met polymorphism and executive
      functioning in patients with bipolar disorder.
AB  - OBJECTIVE: In the present study, we investigate the association between the
      val66met polymorphism of the brain-derived neurotrophic factor (BNDF) and the
      performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian
      patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder
      were assessed and their performance on the Wisconsin Card Sorting Test was
      compared with the allele frequency and genotype of the val66met polymorphism of
      the brain-derived neurotrophic factor. RESULTS: The percentage of non
      perseverative errors was significantly higher among patients with the val/val
      genotype. There was no association between (BNDF) genotype frequency and other
      Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate
      previous descriptions of an association between a worse cognitive performance and
      the presence of the met allele of the val66met brain-derived neurotrophic factor
      gene polymorphism.

PMID- 19578687
TI  - Neuropsychological differences between attention deficit hyperactivity disorder
      and control children and adolescents referred for academic impairment.
AB  - OBJECTIVE: To compare the performances of children and adolescents with attention
      deficit hyperactivity disorder with a group of control comparison subjects, both
      taken from a large clinical sample, using some of the most widely employed
      attention-based Brazilian tests. METHOD: The performances of 186 children and
      adolescents with attention deficit hyperactivity disorder were compared to that
      of 80 control individuals based on attention and working memory scores. Both
      groups had been referred due to academic impairment. All individuals were
      submitted to the TAVIS-3 sustained, shifted and focused attention tests, as well
      as to the working memory tests that make up the WISC-III Freedom from
      Distractibility Index (Digit Span and Arithmetic). RESULTS: The control group was
      slightly older than the attention deficit hyperactivity disorder group (p =
      0.07); IQ and schooling did not differ between groups (p = 0.34 and p = 0.38,
      respectively). While performing a test requiring sustained attention for a longer
      period of time, the attention deficit hyperactivity disorder group showed a
      significantly higher number of commission errors compared to the controls, thus
      presenting sustained attention deficits (p = 0.003); when the influence of IQ,
      age and schooling was reduced, the attention deficit hyperactivity disorder group
      also made more omission errors during a sustained attention task in comparison to
      the control group, thus achieving a borderline significance level (p = 0.08); the
      attention deficit hyperactivity disorder group also performed worse in Digit Span
      forward and backward (p = 0.013 and p = 0.01, respectively) and in Arithmetic (p
      = 0.008). Other scores did not achieve significance. CONCLUSION: Our findings
      suggest that some of the most commonly used Brazilian attention-based tests -
      especially the sustained attention and working memory tests - may be useful to
      help distinguish subjects with attention deficit hyperactivity disorder from
      control subjects.

PMID- 19578688
TI  - The psychiatric side-effects of rimonabant.
AB  - OBJECTIVE: Experimental evidence has suggested that drugs that enhance
      cannabinoid type-1 (CB1) receptor activity may induce anxiolytic and
      antidepressant effects, whilst the opposite has been reported with antagonists.
      Thus, the objective of the present review is to discuss the potential psychiatric
      side-effects of CB1 receptor antagonists, such as rimonabant, which has been
      recently marketed in several countries for the treatment of smoking cessation,
      obesity and associated metabolic disorders. METHOD: Literature searches were
      performed in PubMed and SciELO databases up to February 2009. The terms searched
      were 'obesity', 'rimonabant', 'cannabinoids', 'unwanted effects', 'diabetes',
      'smoking cessation' and 'side-effects'. RESULTS: Clinical trials have revealed
      that rimonabant may promote weight loss in obese patients, although it may also
      induce symptoms of anxiety and depression. DISCUSSION: Patients taking CB1
      receptor antagonists should be carefully investigated for psychiatric side
      effects. These drugs should not be prescribed for those already suffering from
      mental disorders. Nevertheless, the development of new compounds targeting the
      endocannabinoid system for the treatment of several conditions would be necessary
      and opportune.

PMID- 19578689
TI  - A review of psychiatric genetics research in the Brazilian population.
AB  - OBJECTIVE AND METHOD: A large increase in the number of Brazilian studies on
      psychiatric genetics has been observed in the 1970's since the first publications
      conducted by a group of researchers in Brazil. Here we reviewed the literature
      and evaluated the advantages and difficulties of psychiatric genetic studies in
      the Brazilian population. CONCLUSION: The Brazilian population is one of the most
      heterogeneous populations in the world, formed mainly by the admixture between
      European, African and Native American populations. Although the admixture process
      is not a particularity of the Brazilian population, much of the history and
      social development in Brazil underlies the ethnic melting pot we observe
      nowadays. Such ethnical heterogeneity of the Brazilian population obviously
      brings some problems when performing genetic studies. However, the Brazilian
      population offers a number of particular characteristics that are of major
      interest when genetic studies are carried out, such as the presence of isolated
      populations. Thus, differences in the genetic profile and in the exposure to
      environmental risks may result in different interactions and pathways to
      psychopathology.

PMID- 19578690
TI  - [Systematized physical activity and cognitive performance in elderly with
      Alzheimer's dementia: a systematic review].
AB  - OBJECTIVE: Despite the growing evidence of the benefits of physical exercise for
      cognition, there is a controversy about the systematic practice of physical
      activity in patients with Alzheimer's disease. Therefore, the objective of this
      study was to procedure a systematic review of studies that analyzed the effect of
      systematized physical activity on cognitive performance in elderly individuals
      with Alzheimer's disease. METHOD: We conducted a search in PsycINFO, Biological
      Abstracts, Medline, Web of Science, Physical Education and SPORTDiscus Index from
      1990 to 2008, using the following keywords: 'physical activity', 'physical
      therapy', 'exercise', 'fitness', 'aerobic', 'strength', 'intervention',
      'cognition', 'cognitive performance', 'Alzheimer's disease', 'Alzheimer's
      dementia', 'Alzheimer's', and cross-references of selected articles. RESULTS:
      There were found eight studies that met inclusion criteria adopted for the
      present work. These studies showed that systematized physical activity
      contributed to at least improve temporarily some cognitive functions of patients
      with Alzheimer's disease, particularly, attention, executive functions and
      language. CONCLUSION: Unable to establish a protocol of recommendations about the
      type and intensity of systematized physical activity required to produce benefits
      in cognitive functioning. However, the practice of regular systematized physical
      activity appears to contribute to the preservation or improvement of cognitive
      functions in patients with Alzheimer's disease.

PMID- 19578691
TI  - Facial emotion recognition in bipolar disorder: a critical review.
AB  - OBJECTIVE: Literature review of the controlled studies in the last 18 years in
      emotion recognition deficits in bipolar disorder. METHOD: A bibliographical
      research of controlled studies with samples larger than 10 participants from 1990
      to June 2008 was completed in Medline, Lilacs, PubMed and ISI. Thirty-two papers
      were evaluated. RESULTS: Euthymic bipolar disorder presented impairment in
      recognizing disgust and fear. Manic BD showed difficult to recognize fearful and
      sad faces. Pediatric bipolar disorder patients and children at risk presented
      impairment in their capacity to recognize emotions in adults and children faces.
      Bipolar disorder patients were more accurate in recognizing facial emotions than
      schizophrenic patients. DISCUSSION: Bipolar disorder patients present impaired
      recognition of disgust, fear and sadness that can be partially attributed to mood
      state. In mania, they have difficult to recognize fear and disgust. Bipolar
      disorder patients were more accurate in recognizing emotions than depressive and
      schizophrenic patients. Bipolar disorder children present a tendency to misjudge
      extreme facial expressions as being moderate or mild in intensity. CONCLUSION:
      Affective and cognitive deficits in bipolar disorder vary according to the mood
      states. Follow-up studies re-testing bipolar disorder patients after recovery are
      needed in order to investigate if these abnormalities reflect a state or trait
      marker and can be considered an endophenotype. Future studies should aim at
      standardizing task and designs.

PMID- 19578692
TI  - Post-therapy group for pathological gamblers: improvement beyond symptoms.

PMID- 19578693
TI  - Fluoxetine associated with severe extrapyramidal symptoms in a patient with basal
      ganglia lesion.

PMID- 19578694
TI  - [Neuropsychological aspects of bipolar disorder].

PMID- 19578695
TI  - [Internet addiction: perspectives on cognitive-behavioral therapy].

PMID- 19578696
TI  - [Huntington's disease: a negative family history case report demonstrating
      reduction of psychiatric symptoms with olanzapine].

PMID- 19578697
TI  - [Morbid jealousy and obsessive-compulsive disorder (OCD)].

PMID- 19578698
TI  - Sexual compulsion and HIV transmission: a case report.

PMID- 19578699
TI  - Specific language impairment in an adult with type I bipolar disorder: a case
      report.

PMID- 19578703
TI  - High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical
      spastic paraparesis, is also detected in patients with infective dermatitis
      associated with HTLV-1.
AB  - Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus
      type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general
      population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety
      of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis
      associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood
      exudative and infective dermatitis involving mainly the scalp, neck and ears. It
      has recently been observed that 30% of patients with IDH develop juvenile
      HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult
      HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the
      proviral load of 28 children and adolescents with IDH not associated with HAM/TSP
      was determined and the results were compared to those obtained in 28 HTLV-1 adult
      carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients
      was similar to that of patients with HAM/TSP and much higher than that found in
      HTLV-1 carriers. The high levels of proviral load in IDH patients were not
      associated with age, duration of illness, duration of breast-feeding, or activity
      status of the skin disease. Since proviral load is associated with neurological
      disability, these data support the view that IDH patients are at high risk of
      developing HAM/TSP.

PMID- 19578704
TI  - The first report in Brazil of severe infection caused by community-acquired
      methicillin-resistant Staphylococcus aureus (CA-MRSA).
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an
      emergent pathogen in Brazil. However, there are no data on the prevalence of CA
      MRSA. We report here the first well-characterized case of severe life-threatening
      CA-MRSA infection in a child living in Rio de Janeiro city. The patient had many
      complications including hematogenous osteomyelitis and involvement of multiple
      sites requiring drainage of soft-tissue abscess, and pleural and pericardial
      empyema. The MRSA isolates recovered were genotyped using PFGE, SCCmec typing and
      multilocus sequence typing. Disk diffusion tests were performed following
      Clinical and Laboratory Standards Institute recommendations. In addition, the
      presence of Panton-Valentine leukocidin (PVL) was assessed by PCR amplification,
      using specific primers for lukF-pv (encoding for the F subunit of the PVL). The
      bacterial isolates were related to the ST30-SCCmecIV lineage (Oceania Southwest
      Pacific clone), a PVL producer CA-MRSA previously detected in Porto Alegre, RS,
      Brazil. Also, the isolates analyzed were susceptible to all non-beta-lactam
      antibiotics tested. The present report demonstrates that disseminated CA-MRSA
      disease is also occurring in Rio de Janeiro. Thus, the empirical treatment of
      moderate or severe infections suspected of being associated with CA-MRSA needs to
      be reviewed in order to allow prompt initiation of an effective therapy that also
      covers these microorganisms.

PMID- 19578705
TI  - Update on lower urinary tract symptoms.
AB  - Management of incontinence is forever changing, evolving as our understanding of
      the pathophysiology improves. It sometimes feels like a sand castle, as the
      principles of therapy of yesterday are replaced by new modalities, without
      leaving a trace of treatments in which we so firmly believed. This special issue
      of TheScientificWorldJOURNAL: TSW Urology was aimed at new treatments, including
      terminology, the assessment of symptoms and need for urodynamics, pharmacologic
      therapy in the elderly, use of injectable materials, biomaterials to correct
      pelvic organ prolapse and stress urinary incontinence, clinical experiences
      including the costs involved in trying to reduce morbidity, the application of
      techniques to improve long-term outcomes, the use of robotics, and
      neuromodulation of bladder over activity. It is never easy to project what will
      be new and exciting, yet have clinical relevance, as well as some evidence of
      success to put together this special issue on incontinence that offers meaningful
      information.

PMID- 19578706
TI  - A rare case of renal gastrinoma.
AB  - We present a rare case of renal gastrinoma. To the best of our knowledge, only
      one case of renal gastrinoma has been reported in the literature so far. An
      African American male was diagnosed with Zollinger Ellison syndrome at the age of
      15 years, when he underwent surgery for peritonitis secondary to duodenal ulcer
      perforation. Further evaluation was deferred and proton pump inhibitors were
      prescribed. Later evaluation showed a left renal mass. Serum gastrin levels were
      4,307 pg/ml. A CAT scan of the abdomen showed 4- x 4-cm heterogeneous solid mass
      in the interpolar region of the left kidney with central hypodensity.
      Somatostatin scintigraphy confirmed a receptor-positive mass in the same
      location. Nephrectomy was done and the tumor was diagnosed on histopathological
      examination as a gastrinoma. At 6-month follow-up, gastrin levels were 72 pg/ml.
      After a follow-up of 6 years, the patient has no recurrent symptoms.

PMID- 19578707
TI  - Incisional hernia involving the neobladder: technical considerations to avoid
      complications.
AB  - The management of incisional hernia following radical cystectomy (RC) and
      neobladder diversion poses a special challenge. Mesh erosion into the neobladder
      is a potential complication of hernia repair in this setting. We describe our
      experience and steps to avoid this complication. Three patients developed
      incisional hernias following RC involving the neobladder. The incisional hernias
      were repaired by the same surgeon. A systematic dissection and repair of the
      hernias with an onlay dual-layer mesh (made of polyglactin and polypropylene) was
      carried out. The critical steps were placing the polyglactin side of the mesh
      deeper and positioning of an omental flap anterior to the neobladder. The omental
      flap adds a protective layer that prevents adhesions between the neobladder and
      abdominal wall, and prevents erosion of the mesh into the fragile neobladder
      wall. All of these patients had received two cycles of neoadjuvant chemotherapy
      prior to RC. The time duration from RC to the repair of hernia was 7, 42, and 54
      months. No intraoperative injury to the neobladder or other complication was
      noted during hernia repair. The patients were followed after hernia repair for
      20, 22, and 42 months with no recurrence, mesh erosion, or other complications.
      Careful understanding and attention to details of the technique can minimize the
      risk of complications, especially incisional hernia recurrence, injury to the
      neobladder, and erosion of mesh into the neobladder wall.

PMID- 19578708
TI  - The influence of various morphologic and hemodynamic carotid plaque
      characteristics on neurological events onset and deaths.
AB  - A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age
      65.42 +/- 9.21, and a group of 36 patients with 58 symptomatic carotid stenoses
      (SCS), mean age 67.63 +/- 8.79, were analyzed prospectively during a 3-year
      follow-up period. All patients underwent color duplex scan sonography (CDS),
      carotid arteriography, computed tomography (CT) scan, and neurological
      examination. The aim of the study was to analyze the correlation between echo
      plaque morphology (degree and plaque quality), local hemodynamic plaque
      characteristics, ischemic CT findings, and onset of new neurological events and
      deaths. The results analysis showed significantly more ACS in the group of 30-49%
      stenosis (p < 0.001), but significantly more SCS in the group of 70-89% (p <
      0.0001) and > or = 90% stenosis (p < 0.05). Fibrous plaque was more frequent in
      the ACS group (p < 0.001), while ulcerated and mixed plaques were more frequent
      in the SCS group (both p < 0.0001). In the SCS group, a significantly higher
      frequency of increased peak systolic and end diastolic velocities was noted at
      the beginning and end of the study (both p < 0.01), as well as for contralateral
      common (CCA) or internal carotid artery (ICA) occlusion (p < 0.05 and p < 0.01,
      respectively), but reduced carotid blood flow volume (p < 0.05) only at the end
      of the study. In the ACS group, the best correlation with new neurological events
      and deaths was shown with positive CT findings, peak systolic flow velocity over
      210 cm/sec, end diastolic flow velocity over 110 cm/sec, plaque stenosis > or =
      70%, plaque ulceration, mixed plaque (all p < 0.0001); stenosis > or = 50% (p <
      0.001); and reduced carotid blood flow volume (p < 0.05).

PMID- 19578709
TI  - Angiotensin-(1-7) and its effects in the kidney.
AB  - Angiotensin-(1-7) (Ang-[1-7]) is a heptapeptide member of the renin-angiotensin
      system (RAS), and acts as a vasodilator and antagonist of angiotensin II (Ang II)
      in the vasculature. The role of Ang-(1-7) in regulating kidney function is not
      well understood. Within the kidneys, Ang-(1-7) is generated by angiotensin
      converting enzyme 2 (ACE2)-mediated degradation of Ang II, sequential cleavage of
      the precursor angiotensin I (Ang I) by ACE2 and ACE, or the actions of brush
      border membrane peptidases on Ang I. Ang-(1-7) mediates its effects via binding
      to kidney Mas receptors, although some actions may occur via Ang II AT1 or AT2
      receptors. In vitro studies suggest that Ang-(1-7) is an intrarenal vasodilator.
      Ang-(1-7) has been reported to induce either natriuresis/diuresis or sodium and
      water retention, via modulation of sodium transporters in the proximal tubule and
      loop of Henle, and collecting duct water transport. In the proximal tubule, Ang
      (1-7) antagonizes growth-promoting signaling pathways via activation of a protein
      tyrosine phosphatase, whereas in mesangial cells, Ang-(1-7) stimulates cell
      growth via activation of mitogen-activated protein kinases. The phenotype of the
      Mas gene knockout mouse suggests that Ang-(1-7)-signaling events exert
      cardiovascular protection by regulating blood pressure, and by limiting
      production of reactive oxygen species and extracellular matrix proteins. Ang-(1
      7) also protects against renal injury in the renal wrap hypertension model,
      independent of effects on blood pressure. In diabetic nephropathy, however, the
      role of Ang-(1-7) on disease progression remains unclear. In summary, Ang-(1-7)
      and its receptor Mas have emerged as important components of the intrarenal RAS.
      The signaling and downstream effects of Ang-(1-7) in the kidney are complex and
      appear to be cell specific. The body of evidence suggests that Ang-(1-7) is
      protective against endothelial dysfunction or Ang II-stimulated proximal tubular
      injury, although the overall effects on glomerular function require further
      study.

PMID- 19578710
TI  - The rise of environmental analytical chemistry as an interdisciplinary activity.
AB  - Modern scientific endeavour is increasingly delivered within an interdisciplinary
      framework. Analytical environmental chemistry is a long-standing example of an
      interdisciplinary approach to scientific research where value is added by the
      close cooperation of different disciplines. This editorial piece discusses the
      rise of environmental analytical chemistry as an interdisciplinary activity and
      outlines the scope of the Analytical Chemistry and the Environmental Chemistry
      domains of TheScientificWorldJOURNAL (TSWJ), and the appropriateness of TSWJ's
      domain format in covering interdisciplinary research. All contributions of new
      data, methods, case studies, and instrumentation, or new interpretations and
      developments of existing data, case studies, methods, and instrumentation,
      relating to analytical and/or environmental chemistry, to the Analytical and
      Environmental Chemistry domains, are welcome and will be considered equally.

PMID- 19578711
TI  - Effectiveness of the Tier 1 Program of the Project P.A.T.H.S.: findings based on
      the first 2 years of program implementation.
AB  - The Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) is a curricular-based program that attempts
      to promote positive youth development in Hong Kong. In the second year of the
      Full Implementation Phase, 20 experimental schools (N = 2,784 students) and 23
      control schools (N = 3,401 students) participated in a randomized group trial.
      Analyses of covariance and linear mixed models, controlling for differences
      between the two groups in terms of Wave 1 pretest scores, personal variables, and
      random effect of schools, showed that participants in the experimental schools
      had significantly higher positive youth development levels than did participants
      in the control schools at post-test, based on different indicators derived from
      the Chinese Positive Youth Development Scale. The students in the experimental
      schools also displayed a lower level of delinquency, but better school adjustment
      than did students in the control schools. Differences between experimental and
      control participants were also found when students who joined the Tier 1 Program
      and perceived the program to be beneficial were employed as participants of the
      experimental schools.

PMID- 19578712
TI  - Assessment of problem gambling in a Chinese context: the Chinese G-MAP.
AB  - There is a severe lack of instruments to assess problem gambling in Chinese
      people. This study examined the psychometric properties of the Chinese version of
      the Maroondah Assessment Profile for Problem Gambling (Chinese G-MAP), based on
      the responses of eight problem gamblers and 125 pathological gamblers seeking
      help from a problem gambling treatment center. Reliability analyses showed that
      the G-MAP and its related domains and scales were generally internally
      consistent. There are also several lines of evidence suggesting that the Chinese
      G-MAP and the various domains are valid: (a) the various G-MAP domain and scale
      measures were significantly correlated among themselves, (b) the G-MAP measures
      were significantly correlated with pathological gambling behavior assessed by the
      4th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      IV), and (c) the G-MAP total scale and domain measures were able to discriminate
      problem gamblers and pathological gamblers. The present study suggests that the
      Chinese G-MAP possesses acceptable psychometric properties that can be used in
      research and practice settings.

PMID- 19578713
TI  - The pre-capillary segment of the blood-brain barrier and its relation to
      perivascular drainage in Alzheimer's disease and small vessel disease.
AB  - The blood-brain barrier (BBB) is the border between the brain tissue and the
      blood and consists of a pre- and post-capillary and a capillary segment. At
      capillaries protein transport is possible via receptor-mediated endocytosis
      through endothelial cells. At the arteries and veins the BBB is thicker and there
      is, under physiological conditions, no direct transport from the brain tissue to
      the blood or vice versa. Here, extracellular fluid is drained into the
      perivascular space, which is a fluid-filled space between the border of the brain
      tissue, the glia limitans, and that of the vessel wall, the adventitia as well as
      along basement membranes within the vessel wall. In the event of degenerative
      changes in the arterial vessel wall, known as small vessel disease (SVD), leakage
      of plasma proteins into the vessel wall and into the perivascular space occurs.
      Thus, the pre-capillary segment of the BBB is altered and drainage of
      extracellular fluid from the brain tissue competes with the leaking plasma for
      perivascular drainage. Since the amyloid beta-protein (Abeta) is subject of this
      perivascular drainage and accumulates in the brains of Alzheimer's disease (AD)
      patients, an alteration of this drainage system in the course of SVD may support
      the accumulation of Abeta within the brain and, in so doing, the development of
      AD.

PMID- 19578714
TI  - Hypercholesterolemia and 3-hydroxy 3-methylglutaryl Coenzyme A reductase
      regulation during ageing.
AB  - We present here a brief description of the path that cholesterol covers from its
      intestinal absorption to its effect exerted on some enzyme regulation. Some
      mechanisms underlying hypercholesterolemia onset and, in particular, the role and
      the regulation of 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR) during
      adult life and during aging, have been described. In addition some
      pharmacological interventions to control proper HMGR regulation and, in turn,
      cholesterol homeostasis maintenance will be introduced.

PMID- 19578715
TI  - Cardiac expression of Tnnt1 requires the GATA4-FOG2 transcription complex.
AB  - Previous work by us and others has shown that the loss of interaction between
      GATA4 and FOG2 protein partners is embryonic lethal due to heart failure at
      embryonic day (E) 13.5; however, the role of this important protein duo in
      various cardiac compartments (e.g., myocardial, endocardial, or epicardial cells)
      remains to be understood. Although a dual role (both as an activator and a
      repressor) for the GATA4-FOG2 transcriptional complex has been put forward, the
      specific genes under GATA4-FOG2 control in the developing heart have remained
      largely elusive. Since the myocardial-restricted Fog2 re-expression in the Fog2
      null embryos is sufficient to extend their life span, identification of GATA4
      FOG2 target genes in cardiomyocytes could shed light on the molecular mechanism
      of GATA4-FOG2 action in these cells. We report here that cardiac expression of
      slow skeletal troponin T (Tnnt1) strictly depends on the physical interaction
      between GATA4-FOG2 in the myocardium of both atria and ventricles.

PMID- 19578716
TI  - Bmi-1, stem cells and cancer.
AB  - Bmi-1, a polycomb gene family member, plays an important role in cell cycle
      regulation, cell immortalization, and cell senescence. Recently, numerous studies
      have demonstrated that Bmi-1 is involved in the regulation of self-renewal and
      differentiation of stem cells. However, the molecular mechanism underlying this
      biological process remains largely unclear. In the present review, we summarized
      the function of Bmi-1 as a transcriptional regulator of gene expression, with
      particular reference to stem cells.

PMID- 19578718
TI  - Dynamic regulation of glutamic acid decarboxylase 65 gene expression in rat
      testis.
AB  - Glutamate decarboxylase 65 (GAD65) produces gamma-aminobutyric acid, the main
      inhibitory neurotransmitter in adult mammalian brain. Previous experiments,
      performed in brain, showed that GAD65 gene possesses two TATA-less promoters,
      although the significance is unknown. Here, by rapid amplification of cDNA ends
      method, two distinct GAD65 mRNA isoforms transcribed from two independent
      clusters of transcription start sites were identified in post-natal rat testis.
      RT-PCR results revealed that the two mRNA isoforms had distinct expression
      patterns during post-natal testis maturation, suggesting that GAD65 gene
      expression was regulated by alternative promoters at the transcription level. By
      using GAD65-specific antibodies, western blotting analysis showed that the 58-kDa
      GAD65, N-terminal 69 amino acids truncated form of full-length GAD65 protein, was
      developmentally expressed during post-natal testis maturation, suggesting that
      GAD65 gene expression in testis may also be regulated by post-translational
      processing. Confocal immunofluorescence microscopy revealed that GAD65 protein
      was presented in Leydig cells of Day 1 testis, primary spermatocytes and
      spermatids of postnatal of Day 90 testis. The above results suggested that GAD65
      gene expression is dynamically regulated at multiple levels during post-natal
      testis maturation.

PMID- 19578717
TI  - Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co
      activator.
AB  - Mouse zinc finger CCHC domain containing 12 gene (ZCCHC12) has been identified as
      a transcriptional co-activator of bone morphogenetic protein (BMP) signaling, and
      human ZCCHC12 was reported to be related to non-syndromic X-linked mental
      retardation (NS-XLMR). However, the details of how human ZCCHC12 involve in the
      NS-XLMR still remain unclear. In this study, we identified a novel nuclear
      localization signal (NLS) in the middle of human ZCCHC12 protein which is
      responsible for the nuclear localization. Multiple-tissue northern blot analysis
      indicated that ZCCHC12 is highly expressed in human brain. Furthermore, in situ
      hybridization showed that ZCCHC12 is specifically expressed in neuroepithelium of
      forebrain, midbrain, and diencephalon regions of mouse E10.5 embryos. Luciferase
      reporter assays demonstrated that ZCCHC12 enhanced the transcriptional activities
      of activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as
      a coactivator. In conclusion, we identified a new NLS in ZCCHC12 and figured out
      that ZCCHC12 functions as a transcriptional co-activator of AP-1 and CREB.

PMID- 19578719
TI  - Treatment of hepatitis C virus core-positive hepatocytes with the transfer of
      recombinant caspase-3 using the 2',5'-oligoadenylate synthetase gene promoter.
AB  - Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity
      and mortality throughout the world. There is no vaccine available and current
      therapy is only partially effective. Since HCV infects only a minority of
      hepatocytes, we hypothesized that induction of apoptosis might be a promising
      approach for the treatment of hepatitis C. In the present study, recombinant
      caspase-3 gene (re-caspase-3) was used because it has the ability to induce
      apoptosis that is independent of the initiator caspases. An HCV-specific promoter
      is required to regulate the cytotoxic caspase-3 expression in HCV-infected cells.
      It has been reported that HCV core protein can specifically activate the 2',5'
      oligoadenylate synthetase (OAS) gene promoter in human hepatocytes. Therefore, we
      constructed an expression vector consisting of the re-caspase-3 under the OAS
      gene promoter (pGL3-OAS-re-caspase-3) and then investigated its effect on HCV
      core-positive liver cells. It was found that the pGL3-OAS-re-caspase-3 construct
      induced apoptosis in HCV core-positive liver cells, but not in normal liver
      cells. These results strongly suggested that the transfer of the re-caspase-3
      gene under the OAS promoter was a novel targeting approach for the treatment of
      HCV infection.

PMID- 19578720
TI  - cDNA microarray reveals the alterations of cytoskeleton-related genes in
      osteoblast under high magneto-gravitational environment.
AB  - The diamagnetic levitation as a novel ground-based model for simulating a reduced
      gravity environment has been widely applied in many fields. In this study, a
      special designed superconducting magnet, which can produce three apparent gravity
      levels (0, 1, and 2 g), namely high magneto-gravitational environment (HMGE), was
      used to simulate space gravity environment. The effects of HMGE on osteoblast
      gene expression profile were investigated by microarray. Genes sensitive to
      diamagnetic levitation environment (0 g), gravity changes, and high magnetic
      field changes were sorted on the basis of typical cell functions. Cytoskeleton,
      as an intracellular load-bearing structure, plays an important role in gravity
      perception. Therefore, 13 cytoskeleton-related genes were chosen according to the
      results of microarray analysis, and the expressions of these genes were found to
      be altered under HMGE by real-time PCR. Based on the PCR results, the expressions
      of WASF2 (WAS protein family, member 2), WIPF1 (WAS/WASL interacting protein
      family, member 1), paxillin, and talin 1 were further identified by western blot
      assay. Results indicated that WASF2 and WIPF1 were more sensitive to altered
      gravity levels, and talin 1 and paxillin were sensitive to both magnetic field
      and gravity changes. Our findings demonstrated that HMGE can affect osteoblast
      gene expression profile and cytoskeleton-related genes expression. The
      identification of mechanosensitive genes may enhance our understandings to the
      mechanism of bone loss induced by microgravity and may provide some potential
      targets for preventing and treating bone loss or osteoporosis.

PMID- 19578721
TI  - Study on docetaxel-loaded nanoparticles with high antitumor efficacy against
      malignant melanoma.
AB  - Docetaxel (Doc) has extraordinary activities against a variety of solid tumors.
      However, the clinical efficacy of Doc is limited due to its poor solubility, low
      selective distribution, fast elimination in vivo, etc. In the present study, Doc
      was incorporated into the core-shell structure of nanoparticles prepared based on
      our previous work. The obtained docetaxel-loaded nanoparticles (DOCNP) were
      characterized with various biophysical methodologies, and its antitumor efficacy
      against malignant melanoma was evaluated both in vitro and in vivo. Our results
      indicated that Doc could be incorporated into the nanoparticles with high
      encapsulation efficiency (>90%). The incorporated Doc can be released from DOCNP
      in a sustained manner. In vitro cytotoxicity studies indicated that DOCNP could
      effectively kill B16 cells and show a dose- and time-dependent efficacy.
      Furthermore, intratumoral administration revealed that DOCNP has significantly
      higher antitumor effect and lower toxicity to normal cells and tissues than free
      Doc. These results suggest that DOCNP may be a promising drug delivery system in
      therapy for malignant melanoma.

PMID- 19578722
TI  - Regulation of CD11b transcription by decreasing PRC2 and increased acH4 level
      during ATRA-induced HL-60 differentiation.
AB  - Polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27
      on histone H3 (K27me3), plays an important role in many types of stem cell
      differentiation. Here, we try to reveal how PRC2, PRC2-mediated repressive
      histone marker H3K27me3, and active histone marker histone H4 acetylation (acH4)
      regulate the CD11b transcription during alltrans retinoic acid (ATRA)-induced HL
      60 leukemia cell differentiation. By using quantitative real-time polymerase
      chain reaction (qPCR) and western blot analysis, we found that the mRNA and
      protein expression levels of two members of PRC2 were decreased during ATRA
      induced HL-60 differentiation, respectively. When treated with ATRA for 72 h, the
      EZH2 and SUZ12 mRNA levels were decreased to 35% and 38% of the control group,
      respectively. At the same time, the granulocytic mature surface marker CD11b
      expression was increased significantly at mRNA level detected by qPCR and protein
      level detected by flow cytometry. By using chromatin immunoprecipitation assay,
      we compared the local changes in SUZ12 binding and PRC2-mediated H3K27me3 at the
      promoter of CD11b during ATRA-induced HL-60 differentiation. Both the levels of
      SUZ12 binding and PRC2-mediated H3K27me3 at the promoter of CD11b were decreased
      for 4.1 and 3.8 folds, respectively. And we also found the increase in the acH4
      level up to 4 folds after 72 h of ATRA treatment. These results suggested that
      the histone modification including PRC2-mediated repressive histone marker
      H3K27me3 and active histone marker acH4 may involve in CD11b transcription during
      HL-60 leukemia cells reprogramming to terminal differentiation.

PMID- 19578723
TI  - Functional analysis of ScSwi1 and CaSwi1 in invasive and pseudohyphal growth of
      Saccharomyces cerevisiae.
AB  - Here we reported that, in Saccharomyces cerevisiae, deleting Swi1 (ScSwi1), a
      core component in Swi/Snf complex, caused defects of invasive growth,
      pseudohyphal growth, FLO11 expression, and proper cell separation. Re
      introduction of SWI1 into the swi1 mutants could suppress all defects observed.
      We also showed that overproducing Swi1 could suppress the defect of flo8 cells in
      pseudohyphal growth in diploids, but not invasive growth in haploids.
      Overexpression of SWI1 could not bypass the requirement of Ste12 or Tec1 in
      invasive growth or pseudohyphal growth. We concluded that the Swi/Snf complex was
      required for FLO11 expression and proper cell separation, and both the FLO8 and
      STE12 genes should be present for the complex to function for the invasive growth
      but only the STE12 gene was required for the pseudohyphal growth. Ectopic
      expression of Candida albicans SWI1 (CaSWI1) could partially complement the
      defects examined of haploid Scswi1 mutants, but failed to complement the defects
      examined of diploid Scswi1/ Scswi1 mutants. Overexpressing CaSwi1 mitigated
      invasive and pseudohyphal growth defects resulting from deletions in the MAP
      kinase and cAMP pathways. The integrity of S. cerevisiae Swi/Snf complex is
      required for invasive and filamentous growth promoted by overexpressing CaSwi1.

PMID- 19578724
TI  - BMPRII is a direct target of miR-21.
AB  - MicroRNAs (miRNAs) are a type of small non-coding RNAs that regulate cognate mRNA
      expressions at the post-transcriptional stage. Although several miRNAs are known
      to be involved in various biological processes, including developmental timing,
      patterning, embryogenesis, differentiation and organogenesis, growth control, and
      apoptosis, many target genes and the functions of most miRNAs are still unclear.
      Since there is only a partial complementarity between miRNAs and their targets in
      animal cells, it is difficult to identify the specific target genes for a given
      miRNA and elucidate its function. In this study, we confirmed that bone
      morphogenetic protein receptor II (BMPRII) is a direct target of miR-21, and also
      showed that the protein level of BMPRII correlates inversely with the amount of
      miR-21 in PC3 and Lncap cells. These findings suggest that miR-21 may have a
      potential role in regulating the malignancy and metastatic abilities of prostate
      cancer cells and in self-renewal of stem cells by regulating the expression of
      BMPRII.

PMID- 19578725
TI  - Functional and structural alterations induced by copper in xanthine oxidase.
AB  - Xanthine oxidase (XO), a key enzyme in purine metabolism, produces reactive
      oxygen species causing vascular injuries and chronic heart failure. Here,
      copper's ability to alter XO activity and structure was investigated in vitro
      after pre-incubation of the enzyme with increasing Cu(2+) concentrations for
      various periods of time. The enzymatic activity was measured by following XO
      catalyzed xanthine oxidation to uric acid under steady-state kinetics conditions.
      Structural alterations were assessed by electronic absorption, fluorescence, and
      circular dichroism spectroscopy. Results showed that Cu(2+) either stimulated or
      inhibited XO activity, depending on metal concentration and pre-incubation
      length, the latter also determining the inhibition type. Cu(2+)-XO complex
      formation was characterized by modifications in XO electronic absorption bands,
      intrinsic fluorescence, and alpha-helical and beta-sheet content. Apparent
      dissociation constant values implied high- and low-affinity Cu(2+) binding sites
      in the vicinity of the enzyme's reactive centers. Data indicated that Cu(2+)
      binding to high-affinity sites caused alterations around XO molybdenum and flavin
      adenine dinucleotide centers, changes in secondary structure, and moderate
      activity inhibition; binding to low affinity sites caused alterations around all
      XO reactive centers including FeS, changes in tertiary structure as reflected by
      alterations in spectral properties, and drastic activity inhibition. Stimulation
      was attributed to transient stabilization of XO optimal conformation. Results
      also emphasized the potential role of copper in the regulation of XO activity
      stemming from its binding properties.

PMID- 19578726
TI  - How bad is accelerated senescence in consumers of drugs of abuse?
AB  - The aging or senescence process that follows maturation is characterized by time
      related functional decline due to genetic, biochemical, physiological and
      anatomical degeneration in tissues and organ systems with time. Oxidative damage
      to mitochondrial DNA (mtDNA) in the heart and brain is inversely related to
      maximum life span of mammals, suggesting that accumulation of mtDNA damage is
      involved in the various disorders associated with aging, cancer and
      neurodegeneration. The suppression of stem/progenitor cell proliferation also
      contributes to the aging process, by reducing tissue regeneration and repair and
      ultimately reducing longevity. Another important factor is the intracellular
      deposition of lipofuscin granules (age pigment), a non-degradable polymeric
      material accumulated within lysosomes, which ultimately exacerbate oxidative
      stress levels in senescent cells. Drugs of abuse can strongly contribute to these
      senescence accelerating factors in the brain. Methylenedioxymethamphetamine
      ('ecstasy') and methamphetamine were shown to promote deletions in brain mtDNA.
      Concerning stem/progenitor cells, it has been shown that several opiates and
      psychostimulants, including ecstasy, decrease the self-renewal capacity of the
      hippocampus by diminishing the rate of proliferation of neural progenitors and/or
      by impairing the long-term survival of neural precursors. Chronic alcohol
      consumption induces lipofuscin deposition in neurons and heart cells. These facts
      provide interesting hints on the potential of these drugs in accelerating brain
      senescence. While the extent and severity of the contribution of drugs of abuse
      for accelerated senescence remain uncertain, these putative aging effects add up
      to the dark side of drug addiction and undoubtedly require a strong research
      effort in the near future.

PMID- 19578727
TI  - [Influence of personality disorders and consumption patterns on the efficacy of a
      relapse-prevention program for the treatment of alcoholism].
AB  - The purpose of this study is to analyze to efficacy of a cognitive-behavioral
      treatment program, in individual and group format, for people with alcohol
      problems, and to determine the role of some personality variables in the process
      of therapeutic recovery. The sample was made up of 80 patients diagnosed as
      alcoholics, 83.8% of whom were men (n=67) and 16.3% were women (n=13). Mean age
      was 42.73 years, with a standard deviation of 9.63 years. Basically, we found a
      high incidence of obsessive-compulsive personality disorder and consumption
      patterns that change as a function of the presence or absence of personality
      disorders. We also observed that the results varied in relation to physiological
      variables and environmental situations associated with the presence of craving
      responses. Treatment of such patients with dual pathology demands greater effort
      from the therapist to promote treatment adherence, an aspect crucial to
      completion of treatment programs and to achieve therapeutic success. Cognitive
      behavioral intervention for relapse prevention was observed to produce
      satisfactory results in patients with personality disorders. Neither consumption
      patterns nor personality disorders predict the type of treatment termination.

PMID- 19578728
TI  - [Impact of a training in brief intervention. Differences in the hospital approach
      of tobacco and alcohol consumption].
AB  - OBJECTIVE: To evaluate th e impact of a training intervention To evaluate the
      impact of a training intervention for health care professionals on inpatients'
      smoking and alcohol consumption and to compare the hospital intervention for the
      two substances. METHODS: Through two parallel studies, we compared, using auto
      administered questionnaires, the referred clinical behaviour on smoking of 66
      health care professionals and the intervention received by 169 patients, with the
      clinical behaviour on hazardous drinking of other 38 professionals and other 118
      patients from different hospital wards before and after attending a training in
      brief intervention on smoking cessation and hazardous alcohol drinking
      respectively. RESULTS: We only found slight differences between alcohol and
      tobacco concerning professionals' behaviour. Professionals declared to assist
      more often patients with alcohol risk consumption than smoking (36.4% vs 10.9%
      [p<.0001]) although with patients those differences haven't been confirmed. They
      just told to have been asked more often about alcohol consumption than about
      smoking (43.6% vs 30.8% [p<.05]). There were no differences after the training
      sessions. DISCUSSION: Before and after training, health professionals hardly
      intervene in patients with alcohol or tobacco consumption even we observed higher
      detection and assist for alcohol risk consumption. It is necessary to examine
      other barriers to the application of the knowledge gained.

PMID- 19578729
TI  - [Neuropsychological profile in cocaine addiction: issues about addict's social
      environment and predictive value of cognitive status in therapeutic outcomes].
AB  - INTRODUCTION AND OBJECTIVE: This study analyses the neuropsychological profile of
      a sample of cocaine addicts and compares it with a control group from the same
      social environment. Also, it explores the predictive power of some
      neuropsychological tests on treatment outcome six months after the exploration.
      PARTICIPANTS AND METHOD: We administered a neuropsychological battery to 30
      patients with a diagnosis of cocaine abuse or cocaine dependence, and to 30
      control participants with no history of drug abuse from the same social
      environment. RESULTS: Verbal learning (p<0.001), immediate visual memory
      (p<0.05), attentional resources management (p<0.05), phonologic fluency (p<0.01),
      abstraction (p<0.001), complex problem-solving (p<0.05) and mental flexibility
      (p<0.05) are the functions most affected by cocaine use. DISCUSSION AND
      CONCLUSIONS: The alterations found in the addict participants were small and non
      pathognomonic, though the deficits can be correlated with impact on quality of
      life and on everyday occupational performance. The neuropsychological exploration
      showed a certain predictive capacity of abstinence after 6 months (the addict
      participants with better verbal mnesic performance and greater mental flexibility
      at the beginning of the treatment seem to benefit more from this). Finally, the
      results suggest that addicts live in a cognitively poor social environment. It is
      suggested that drug use increases previous deficits, probably of an educational
      or environmental origin, that are common to their immediate social context.

PMID- 19578730
TI  - [Christmas work dinners. A pattern of recreational use of alcohol and other
      drugs?].
AB  - The aim of this study was to develop an exploratory approach to characterizing
      the pattern of recreational abuse of alcohol and other drugs abuse at Christmas
      work dinners. An adaptation of the rapid assessment methodology RARE was carried
      out through the combination of quantitative (rapid assessment surveys, n=444) and
      qualitative (observations and semistructured interviews, n=8) techniques. The
      fieldwork was carried out at 13 restaurants in Valencia and Alicante (Spain) in
      December 2007. In general we observed a marked increase in the use of alcohol and
      other substances compared to the rest of the year, though restaurant staff
      perceived a decrease in alcohol abuse attributable to new road traffic
      legislation. Cocaine is perceived as the illicit substance most widely used at
      such events. Younger coworkers initiate older ones in the use of illicit drugs,
      and the the latter may use this behaviour as a means of feeling younger and more
      uninhibited. Christmas work dinners propitiate a recreational substance-use
      pattern that requires adapted preventive and restrictive interventions, such as
      the introduction of suitable transport initiatives and the restriction of alcohol
      serving hours.

PMID- 19578731
TI  - [Benzodiazepine use in a sample of patients on a treatment program with opiate
      derivatives (PTDO)].
AB  - OBJECTIVES: Benzodiazepines (BZ) are widely prescribed drugs, but their use is
      controversial in patients who present a disorder caused by substance use/abuse,
      due to the risk of tolerance and abuse/dependence. The purpose of this work is to
      determine the levels of BZ use in patients treated with methadone and to compare
      them with findings from the current literature. METHODOLOGY: a sample of 43
      patients was selected; inclusion criterion was being on the PTDO (treatment
      program with opiate derivatives) at the UAD (Drug-dependence unit) in Monforte de
      Lemos (Lugo-Spain). Demographic and use variables were analyzed. Data collection
      and subsequent analysis were carried out using the statistical program SPSS 12.0.
      RESULTS: 46.5% of the patients take BZ, and of these, 60% are over age 45. The
      most widely used of these is alprazolam (p<0.001), and 70% take just one active
      ingredient. The main prescriber is the general practitioner, and the most
      frequent indication is insomnia. DISCUSSION AND CONCLUSIONS: BZ-use data and
      their relationship to time spent on methadone are similar to those of other
      published studies. Despite the recommendation to use long half-life BZ in
      patients with substance abuse disorders, it is striking that in the case studied
      here the most widely prescribed type is alprazolam.

PMID- 19578732
TI  - [Relationship between physical self-concept and alcohol and tobacco use
      behaviours in adolescents].
AB  - The purpose of this study was to analyze the effects of gender, alcohol use,
      smoking behaviour and the practice of sport on physical self-concept among
      Spanish students of physical education. A total of 1,008 students (M age=15.94,
      SD=89) participated in the study, and completed the physical self-concept
      questionnaire (PSQ). The results revealed that physical self-concept was related
      to gender, alcohol use, smoking behaviour and the practice of sport. The best
      perception of body image was found in women who did not smoke and participants
      (male and female) who did not do sport. On the other hand, being male and
      practicing sport predicted general physical self-concept. This study shows the
      relevance of the belief that smoking is associated with good body image and that
      sport is practiced to improve physical appearance.

PMID- 19578733
TI  - [Spanish version of the Dysexecutive Questionnaire (DEX-Sp): psychometric
      properties in addicts and non-clinical sample].
AB  - OBJECTIVE: Several studies have shown evidence of executive function impairment
      associated with substance abuse. This suggests the potential usefulness of a
      baseline assessment measure to screen for dysexecutive impairments in individuals
      beginning treatment. The Dysexecutive Questionnaire (DEX) is a test widely used
      to estimate executive dysfunction. The main objective of this work is to study
      the psychometric properties of the Spanish version of the Dysexecutive
      Questionnaire (DEX-Sp). A complementary goal is to study its potential utility
      for initial screening in addicted individuals seeking treatment. METHOD: A sample
      of 131 non-clinical and 127 clinical individuals meeting the DSM-IV-TR substance
      abuse or dependence criteria were recruited. RESULTS: Internal consistency of the
      questionnaire was assessed (Cronbach's Alfa=0.91), as well as other reliability
      indicators. Exploratory and confirmatory factor analysis offers four- and five
      factor solutions. Also tested were the dimensionality and structural model and
      its convergent and discriminant validity with other instruments. Differences
      between clinical and non-clinical individuals and total scores were also
      analyzed. CONCLUSIONS: The data suggest that the Spanish version of the DEX is a
      useful measure for assessing general symptoms of dysexecutive syndrome, and a
      valid, reliable and adequate screening test for estimating cognitive impairment
      associated with substance abuse.

PMID- 19578734
TI  - [Concomitant lithium and methadone treatment in a bipolar patient: a case
      report].
AB  - Dual diagnosis requires complex therapeutic approaches to adapt treatment to the
      dual nature of the problem. It is important to understand the drug effects and
      the drug interactions that may be observed during the integral treatment of these
      pathologies. Given the scarcity of data on the effects of lithium and methadone
      treatment, the aim of this clinical case report is to explain the interactions
      produced between methadone and lithium carbonate, in a female patient with
      medical multi-pathology, opioid-dependent and with comorbid bipolar disorder, who
      was treated with both drugs. The most common adverse effects for each drug are
      described. Drug interactions and temporal correspondence of the two drugs, as
      well as their dosages, are described through review of the retrospective chart
      and prospective follow-up of the patient. After one year of follow-up the patient
      had experienced no interactions in the concomitant lithium and methadone
      treatment. It should be noted that treatment of bipolar patients with dual
      diagnosis is complex, and should only be carried out by experts.

PMID- 19578735
TI  - The 'timely' development of Rexin-G: first targeted injectable gene vector
      (review).
AB  - In an age where we can i) know precisely where a misplaced automobile resides by
      its global positioning, ii) send mechanistic probes to Mars with pinpoint
      accuracy, iii) calculate exactly how many mutations are required to create (i.e.,
      to transform) a cancer cell, and iv) determine how many fewer genes it takes to
      develop a human being than it does a rice plant, it is difficult to fathom the
      previously unanswered question: 'Whatever happened to the promise and potential
      of cancer gene therapy?' This review answers that question with a resounding
      clinical denouement. In addition, it provides a 'Cooks tour' of applied molecular
      genetics and nanotechnology as these fields relate to the development of Rexin-G
      the world's first tumor-targeted genetic medicine to be fully validated in the
      clinic. The commentary will expose certain fallacies and ideologies that have
      retarded the progress of cancer gene therapy as it advances our instruments and
      understanding of the finespun fabric of our nature.

PMID- 19578736
TI  - The role of hepatocyte growth factor activator inhibitor-1 (HAI-1) as a
      prognostic indicator in cervical cancer.
AB  - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type serine
      protease inhibitor that has a broad inhibitory spectrum against serine proteases.
      This is the first study to investigate the role of HAI-1 and its clinical
      importance in cervical cancer. We attempted to investigate the inhibitory effects
      of HAI-1 using cervical carcinoma cell lines SiHa with integrated human
      papillomavirus (HPV) 16 and HeLa with integrated HPV 18. HAI-1 expression in
      cervical cancer (n=91) were assessed by immunohistochemistry. HAI-1 was found to
      be a potential inhibitory effects mediated by reduction of hepsin, matriptase and
      prostasin expression. This led to apoptosis through a reduction in the levels of
      Bcl-2, Bcl-xL, MUPP-1 and MAGI-3 in cervical cancer cell lines. There were
      significant correlations between HAI-1 expression and stage (p=0.013), tumor size
      (p=0.002), stromal invasion (p<0.001), vaginal invasion (p=0.031), parametrial
      invasion (p=0.012), lymph-node metastasis (p=0.019), and LVS involvement
      (p=0.002). The disease-free and overall survival rates of patients exhibiting
      high HAI-1 expression were significantly higher than those of patients exhibiting
      low HAI-1 expression (p=0.022 and p=0.011, respectively). The present study
      proposes that these findings may be considered HAI-1 as a therapeutic target for
      treatment and identify as a favorable prognostic marker for cancer patients of
      cervical cancer.

PMID- 19578737
TI  - Anti-tumor effects of fusion cells of type 1 dendritic cells and Meth A tumor
      cells using hemagglutinating virus of Japan-envelope.
AB  - It has been reported that the fusion cells of dendritic cells (DCs) and tumor
      cells have anti-tumor effects. In this experiment, we examined the anti-tumor
      effects of fusion cells of bone marrow-derived DC type 1 (DC1) and irradiated
      tumor cells using a newly commercially available hemagglutinating virus of Japan
      envelope (HVJ-E) after cell fusion, in a mouse model. To induce DC1, bone marrow
      cells (BMCs) from BALB/c mice were cultured with GM-CSF, IL-12 and IFN-gamma. BMC
      derived DC1 were fused with 20-Gy-irradiated Meth A cells (BALB/c-derived
      fibrosarcoma) using HVJ-E. We subcutaneously injected: i) the BMC-derived DC1, or
      ii) the fusion cells of the DC1 and the irradiated Meth A cells, into Meth A
      bearing BALB/c mice. The injection of only DC1 showed a moderate anti-tumor
      effect, as we previously described. However, the fusion cells were more effective
      in not only suppressing tumor growth but also prolonging survival. These results
      suggest that the fusion cells of DC1 and the irradiated tumor cells using HVJ-E
      were more effective in tumor suppression than DC1 alone.

PMID- 19578739
TI  - The feasibility of using biopsy samples from esophageal cancer for comprehensive
      gene expression profiling.
AB  - Advanced esophageal cancer has been recently treated by multimodal therapy
      including preoperative chemotherapy or chemoradiotherapy and surgery. A biopsy
      sample provides a valuable specimen for understanding the biological
      characteristics of individual esophageal cancer. Pretreatment prediction of the
      response to chemotherapy or radiotherapy based on biological characteristics
      using biopsy samples is a desirable goal. In using biopsy samples for molecular
      analysis, there are two problems; the proportion of cancer cells and the
      intratumor heterogeneity. This study was conducted to investigate the feasibility
      of using endoscopic biopsy samples of esophageal squamous cell cancer (ESCC) for
      comprehensive gene expression profiling (GEP). Comprehensive GEP was performed in
      40 bulky ESCC specimens and 10 normal esophageal epithelial specimens from
      patients who underwent esophageal resection and 52 endoscopic ESCC biopsy samples
      from 26 patients (two samples per one patient). Unsupervised hierarchical cluster
      analysis showed distinct profiles between the bulky ESCC specimens and normal
      epithelial specimens. Also, unsupervised hierarchical cluster analysis revealed
      distinct profiles between the biopsy ESCC samples and normal epithelial
      specimens. Moreover, a couple of biopsy samples taken from different locations of
      the same tumor were closely clustered together. That is, biopsy ESCC samples were
      distinguished from normal esophageal epithelial specimens and the intratumor
      heterogeneity of GEP was smaller than intertumor heterogeneity. GEP using biopsy
      ESCC samples is feasible and has the potential to represent the biological
      properties.

PMID- 19578738
TI  - MMP-2 downregulation mediates differential regulation of cell death via ErbB-2 in
      glioma xenografts.
AB  - The epidermal growth factor receptor (EGFR) family (also known as the ErbB
      protein family) is comprised of four structurally-related receptor tyrosine
      kinases. Insufficient ErbB signaling in humans is associated with the development
      of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's
      disease. In contrast, excessive ErbB signaling is associated with the development
      of a wide variety of solid tumors. ErbB-1 and -2 are found in many human cancers
      and their excessive signaling may be critical factors in the development and
      malignancy of solid tumors. Several molecular strategies have been developed
      recently to modulate either EGFR or the downstream signal beyond the cell surface
      receptor. In the present study, we used human EGFR-overexpressing glioma
      xenograft cells 4910 and 5310 and targeted MMP-2 expression using an adenoviral
      RNAi construct. We observed that the RNAi-mediated downregulation of MMP-2 causes
      the upregulation of ErbB-2 in certain EGFR-overexpressing glioma xenograft cells
      both in vitro and in vivo. Targeted MMP-2 downregulation was observed in a dose
      dependent manner with no apparent off-target effects in these xenograft cells. We
      also noted that the overexpression of ErbB-2 induced by MMP-2 downregulation is
      consistent with p50-mediated cell death in 5310 cells but not in 4910 cells. In
      addition, APAF-1 expression levels increased in correlation with increased ErbB-2
      expression after MMP-2 downregulation in vitro and in vivo. Our results suggest
      that MMP-2 may play a role in a hitherto unknown signaling pathway mediated via
      ErbB-2 in certain cancer cell types.

PMID- 19578740
TI  - Resistance to cytotoxic chemotherapy-induced apoptosis in side population cells
      of human oral squamous cell carcinoma cell line Ho-1-N-1.
AB  - Side population (SP) cells are isolated from various tissues and cell lines based
      on the exclusion of DNA-binding dye Hoechst 33,342 and exhibit potent stem cell
      characteristics. There have been few previous reports of SP cells in head and
      neck cancer cell lines. Thus, we isolated SP cells from oral squamous cell
      carcinoma cell line, Ho-1-N-1. Ho-1-N-1 contained 3.0% SP cells. Ho-1-N-1 SP
      cells showed self-renewal capacity, generating both SP and non-SP cells. Next, we
      analyzed differentially expressed genes between Ho-1-N-1 SP and non-SP cells
      using GeneChip microarray and quantitative real-time RT-PCR. SP cells expressed
      high levels of ATP-binding cassette transporters with related multidrug
      resistance (MDR) genes. The expression of ABCB1 and ABCG2 were significantly up
      regulated in Ho-1-N-1 SP cells. In addition, the expression of CFLAR, BCL2 and
      BCL2A1 which are associated with anti-apoptosis, were also significantly
      increased in the SP cells. Chemoresistance to anticancer agents, including 5
      fluorouracil and carboplatin, were compared between Ho1-N-1 SP and non-SP cells
      using flow cytometry and tetrazolium salt microtiter plate assay. Ho-1-N-1 SP
      cells survived significantly longer and SP ratio remarkably increased after
      anticancer agent treatment compared to non-SP cells. Immunocytochemical staining
      and apoptosis assay validated these results, and suggested an anti-apoptotic
      potential for Ho-1-N-1 SP cells. Ho-1-N-1 SP cells survived with various agents
      which were not only probably due to high level expression of ABC transporters,
      but also anti-apoptotic proteins. These observations indicated that Ho-1-N-1 SP
      cells were MDR phenotype and should be the main target for effective cancer
      therapy.

PMID- 19578741
TI  - Polymer-conjugated guanidine is a potentially useful anti-tumor agent.
AB  - Guanidine compounds have important biochemical properties. Aminoguanidine, as an
      example, is an anti-oxidant, a nitric oxide synthase inhibitor (NOS) which
      prevents nitric oxide formation, and an inhibitor of advanced glycosylation end
      products (AGEs). As an anti-oxidant, aminoguanidine may affect the formation of
      atherosclerotic lesions through protection from LDL oxidation. Inhibition of AGEs
      could have a preventive effect on the tissue damage caused by diabetes where AGEs
      are considered to be an important factor. The role of NO in cancer is complex and
      not fully understood, but it may have influence on growth and progression. In
      this study, the tumor growth inhibitory effect of conjugated guanidine (i.e. a
      polyguanidine) was investigated. The effect on tumor cell growth was studied in
      cultures of prostate, breast, bladder and renal cell cancer, and a fluorometric
      cytotoxicity assay was performed. Guanidine conjugates were prepared by reacting
      aminoguanidine or agmatine with periodate oxidized dextran followed by reductive
      amination. The cytotoxic effect was compared with an anthracycline (adriamycin).
      The dextran-guanidine conjugates were cytotoxic at low micromolar concentrations,
      and the dextran-aminoguanidine conjugate (GDC) had the highest efficacy, being
      more efficient than adriamycin, in all of the tested tumor cell lines. Breast and
      prostate cancer cells were the most sensitive. At 0.5 microM, GDC killed >95% of
      the breast cancer cells compared to 25% for Adriamycine. In prostate cancer
      cells, GDC killed approximately 55% of the cells at 0.1 microM and 100% of the
      cells at 0.5 microM compared to approximately 22 and approximately 62%,
      respectively, for adriamycin. Unconjugated aminoguanidine and agmatine did not
      seem to affect tumor cell growth even at high concentrations (mM). Polymer-
      conjugated guanidine is a potentially useful template for the construction of
      therapeutic tumor targeting cytotoxic agents.

PMID- 19578742
TI  - Cholangiocarcinomas associated with long-term inflammation express the activation
      induced cytidine deaminase and germinal center-associated nuclear protein
      involved in immunoglobulin V-region diversification.
AB  - Cholangiocarcinoma (CCA) represents a model of tumor development after long-term
      inflammation which causes DNA damage or impairs DNA repair mechanism. AID and
      GANP, both appearing in antigen-driven B cells, are involved in affinity
      maturation of the immunoglobulin V-region with increased somatic mutation. A
      normal cholangiocyte line showed the induction of AID transcripts after
      stimulation with TNF-alpha, whereas ganp transcripts appeared constitutively in
      this cell line. Next, we examined the expression of AID and GANP in clinical CCA
      specimens to obtain information whether their expression levels are associated
      with the malignant grade of CCA. AID expression was similarly detected in the
      clinical cases of both well-differentiated and poorly-differentiated CCAs. On the
      contrary, GANP expression was detected in CCA cells at a higher level in the
      nucleus of poorly-differentiated CCAs with shorter survivals than in that of well
      differentiated CCAs. The high and low cases of nuclear GANP expression showed no
      change in the frequency of the TP53 mutations, however, further investigation by
      in vitro experiment demonstrated that the high GANP expression caused the
      increased number of gammaH2AX foci after DNA damage by ionizing-irradiation.
      These results suggest that GANP is involved in regulation of DNA repair mechanism
      and the abnormal over-expression of GANP together with AID might be associated
      with rigorous DNA damage, potentially causing the malignant development of CCAs
      during long-term inflammation.

PMID- 19578743
TI  - Lymphatic metastasis of breast cancer cells is associated with differential gene
      expression profiles that predict cancer stem cell-like properties and the ability
      to survive, establish and grow in a foreign environment.
AB  - Although lymphatic dissemination is a major route for breast cancer metastasis,
      there has been little work to determine what factors control the ability of tumor
      cells to survive, establish and show progressive growth in a lymph node
      environment. This information is of particular relevance now, in the era of
      sentinel lymph node biopsy, where smaller intranodal tumor deposits are being
      detected earlier in the course of disease, the clinical relevance of which is
      uncertain. In this study, we compared differentially expressed genes in cell
      lines of high (468LN) vs. low (468GFP) lymphatic metastatic ability, and related
      these to clinical literature on genes associated with lymphatic metastatic
      ability and prognosis, to identify genes of potential clinical relevance. This
      approach revealed differential expression of a set of genes associated with
      'cancer stem cell-like' properties, as well as networks of genes potentially
      associated with survival and autonomous growth. We explored these differences
      functionally and found that 468LN cells have a higher proportion of cells with a
      cancer stem cell-like (CD44+/CD24-) phenotype, have a higher clonogenic potential
      and a greater ability to survive, establish and grow in a foreign (lymph node and
      3D Matrigel) microenvironment, relative to 468GFP cells. Differentially expressed
      genes which reflect these functions provide candidates for investigation as
      potential targets for therapy directed against early lymphatic metastasis.

PMID- 19578744
TI  - Human papillomavirus type 16 oncoprotein E7 suppresses cadherin-mediated cell
      adhesion via ERK and AP-1 signaling.
AB  - Human papillomaviruses (HPV) are the main etiological factor for cervical
      carcinoma. HPV-16 is the most prevalent high-risk HPV-genotype found in HPV
      associated cancers. We studied the effect of HPV-16 E7 oncoprotein on cadherin
      mediated cell adhesion. The expression of E7 strongly suppressed the cadherin
      mediated cell adhesion in the rat fibroblast cell line 3Y1. This suppression was
      associated with the decreased expression of N-cadherin at the transcriptional
      level. The treatment of 3Y1 cells that express E7 (E7-3Y1) with MEK inhibitor
      recovered the cadherin-mediated cell adhesion together with the accumulation of N
      cadherin at the cell-cell contact site. Moreover, the suppression of c-Jun, which
      is the element of AP-1 transcriptional factor, leads to the recovery of N
      cadherin expression and cadherin-mediated cell adhesion in E7-3Y1 cells. Taken
      together, our results demonstrate that E7 regulates cadherin-mediated cell
      adhesion through the modulation of cadherin expression via the MEK-ERK and AP-1
      signaling pathway.

PMID- 19578746
TI  - Chromosomally and microsatellite stable colorectal carcinomas without the CpG
      island methylator phenotype in a molecular classification.
AB  - We hypothesized that in a comprehensive analysis of colorectal carcinomas (CRC)
      the three currently known major molecular mechanisms of carcinogenesis (i.e.,
      chromosomal instability, microsatellite instability, and CpG island methylator
      phenotype, CIMP) would associate with the molecular features indicative of these
      pathways, allowing a molecular classification. A prospectively collected
      clinicopathologically well-characterized series of 130 CRCs was tested for
      chromosomal instability (DNA-flow cytometry and analysis of allelic imbalance
      with microsatellite markers 5q21, 8p21, 9q21, 17p13, and 18q21), microsatellite
      instability (Bethesda panel), CIMP (MethyLight), and mutations of K-ras, B-raf,
      APC, and p53. Morphology was reviewed, and nuclear beta-catenin translocation was
      assessed by immunohistochemistry. Based on the molecular features, sporadic high
      degree microsatellite instable tumours, tumours of the hereditary non-polyposis
      coli carcinoma syndrome, and 'sporadic standard-type' CRC could be delineated
      (14, 4, and 55, respectively). However, overlap between classes was seen for 46
      of the remaining tumours where widespread or occasional methylations (excluding
      MLH1) were observed, and the majority had chromosomal instability. Importantly, a
      group of 11 tumours was observed without either microsatellite or chromosomal
      instability, nor any methylation. Morphologically, these tumours were without any
      distinguishing features, all had tumour budding and 10 showed nuclear beta
      catenin translocation. Overall, the data give an overview of the molecular
      classes in CRC that should be taken into account in studies on carcinogenesis and
      clinicopathological studies. Specifically, the absence of CIN, MSI, and CIMP in
      an 8.46% fraction of tumours delineates a group to be aware of.

PMID- 19578745
TI  - Halofuginone mediated protection against radiation-induced leg contracture.
AB  - Fibrosis of normal tissues often accompanies radiation treatment of cancer.
      Activation of the transforming growth factor-beta (TGF-beta) signaling pathway is
      thought to play a major role in radiation-induced fibrosis and has prompted the
      development and assessment of low molecular weight inhibitors of the pathway.
      Previous studies with halofuginone have shown it to inhibit TGF-beta signaling in
      vitro and protect mice from radiation-induced leg contraction (a model for soft
      tissue fibrosis). The current study confirms these findings for HaCaT cells
      stimulated with exogenous TGF-beta treatment. Reducing the halifuginone treatment
      from 7 days/week (used previously) to 5 days/week post-radiation exposure
      provided significant protection against radiation-induced leg contraction in mice
      3 and 4 months post-radiation treatment. Halofuginone treatment was shown to
      attenuate TGF-beta signaling molecules taken from irradiated skin including TGF
      betaRII, pSmad3, Smad7, and TSP1. The latter, TSP1, a co-activator of TGF-beta
      may serve as a suitable biomarker for monitoring the efficacy of halofuginone
      should it be evaluated in a clinical setting for protection against radiation
      induced fibrosis.

PMID- 19578747
TI  - hTERT promotes the invasion of telomerase-negative tumor cells in vitro.
AB  - Telomerase activation is a common feature of most types of human cancers.
      Although several studies have shown that activation of telomerase might
      participate in the progression of tumors, the mechanism by which telomerase
      activation causes the invasion and metastasis of tumors remains unclear. In this
      study, we transfected a vector containing the full-length cDNA of hTERT into a
      telomerase-negative osteosarcoma cell line U2OS (hTERT/U2OS). Vacant vector
      transfected U2OS cells served as a control (EGFP/U2OS). We then compared the
      biological and vitodynamic changes in these transfected and untransfected U2OS
      cells. The hTERT protein was detected in hTERT/U2OS cells by Western blot
      analysis and immunochemistry assay. The telomere length in hTERT/U2OS cells was
      longer than that in EGFP/U2OS and untransfected U2OS cells. We also found using
      vacuum micropipette aspiration that hTERT transfection did not only promote the
      proliferation of hTERT-transfected U2OS cells but also increased the cellular
      adhesion capacity to the extracellular matrix. Transwell matrigel assay confirmed
      an increased invasion ability in hTERT/U2OS cells. These results strongly suggest
      that hTERT transfection promotes the invasion of telomerase-negative cells.
      Telomerase-mediated telomere maintenance enables these cells to achieve a fully
      malignant endpoint, including invasion and metastasis.

PMID- 19578748
TI  - MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and
      invasion.
AB  - Signal transducer and activator of transcription 3 (STAT3) is aberrantly
      activated in human cancer including lung cancer and has been implicated in
      transformation, tumorigenicity, and metastasis. One putative downstream gene
      regulated by Stat3 is MUC1 which also has important roles in tumorigenesis. We
      determined if Stat3 regulates MUC1 in lung cancer cell lines and what function
      MUC1 plays in lung cancer cell biology. We examined MUC1 expression in non-small
      cell lung cancer (NSCLC) cell lines and found high levels of MUC1 protein
      expression associated with higher levels of tyrosine phosphorylated STAT3. STAT3
      knockdown downregulated MUC1 expression whereas constitutive STAT3 expression
      increased MUC1 expression at mRNA and protein levels. MUC1 knockdown induced
      cellular apoptosis concomitant with reduced Bcl-XL and sensitized cells to
      cisplatin treatment. MUC1 knockdown inhibited tumor growth and metastasis in an
      orthotopic mouse model of lung cancer by activating apoptosis and inhibiting cell
      proliferation in vivo. These results demonstrate that constitutively activated
      STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and
      metastasis in vitro and in vivo. MUC1 appears to be a cooperating oncoprotein
      with multiple oncogenic tyrosine kinase pathways and could be an effective target
      for the treatment of lung cancer.

PMID- 19578749
TI  - Use of IHC and newly designed matriptase inhibitors to elucidate the role of
      matriptase in pancreatic ductal adenocarcinoma.
AB  - Matriptase, also known as MT-SP1, is a type II transmembrane serine protease
      strongly implicated in both the development and progression of a variety of
      epithelial cancers. Evidence comes from studies of its expression in human
      cancers and from mouse models of spontaneous cancer. Matriptase is considered to
      be a major activator of two key stimulators of invasive growth, namely hepatocyte
      growth factor/scatter factor and urokinase-type plasminogen activator. The aim of
      this study was to examine the role of matriptase in pancreatic ductal
      adenocarcinoma by expression analysis and functional assays in vitro.
      Immunohistochemical analysis of matriptase performed on microtissue arrays and
      large samples of 55 pancreatic ductal adenocarcinomas and on 31 samples of normal
      pancreatic ducts revealed that although matriptase expression differed greatly in
      both malignant and normal ductal pancreatic tissue, matriptase scores were
      significantly (p=0.02) elevated in pancreatic ductal adenocarcinoma compared to
      normal pancreatic ducts. To evaluate the role of matriptase during development of
      pancreatic cancer, we studied the effects of newly designed matriptase inhibitors
      on the processing of the zymogen of urokinase-type plasminogen activator in the
      human adenocarcinoma cell lines AsPC-1 and BxPC-3. In both cell lines, at 1
      microM, all matriptase inhibitors completely prevented zymogen activation. At
      lower inhibitor concentrations, the degree of inhibition of zymogen processing
      correlated with the affinities of the inhibitors towards matriptase indicating
      that this is a specific result of matriptase inhibition. Furthermore, matriptase
      inhibitors reduced the phosphorylation of the HGF receptor/cMet and the overall
      cellular invasiveness of the human pancreatic adenocarcinoma cell line AsPC-1.
      Our findings demonstrate for the first time that matriptase may be involved in
      the progression of pancreatic ductal adenocarcinoma and that matriptase
      inhibition may contribute to preventing the progression of this devastating
      disease.

PMID- 19578750
TI  - Down-regulation of the apoptosis-inducing factor or Bcl-2 inhibitor of
      transcription by RNA interference can alleviate TAp63gamma-induced apoptosis in
      esophageal squamous carcinoma EC9706 cells.
AB  - In this communication, the roles of apoptosis-inducing factor (AIF) and Bcl-2
      inhibitor of transcription (Bit1) in TAp63gamma-induced apoptosis were
      investigated in human esophageal squamous cancer EC9706 cells. Positive RNA and
      protein expressions of AIF and Bit1 in these cells were verified. However, no
      TAp63gamma could be detected. Transfection of expression vector pcDNA3.1
      TAp63gamma into EC9706 resulted in TAp63gamma expression, and peak level
      apoptosis was observed 24 h after the transfection disclosed by DNA fragmentation
      assay. In addition, it was found with Western blot that AIF and Bit1 were
      released into cytosol from mitochondria, and AIF was further translocated into
      nucleus, during the stage of TAp63gamma-induced cell apoptosis. Down-regulation
      of either AIF or Bit1 by RNA interference could, however, alleviate TAp63gamma
      induced cell apoptosis. In conclusion, TAp63gamma could induce apoptosis in human
      esophageal squamous cancer EC9706 cells, through at least releasing AIF and Bit1
      from mitochindria into cytosol and nucleus, where apoptotic cascade takes place.
      These findings indicate that mitochondria-released proapoptotic proteins, AIF and
      Bit1, are important factors in a TAp63gamma-induced EC9706 cell apoptosis
      pathway.

PMID- 19578751
TI  - Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine
      needle aspiration biopsy.
AB  - Fine needle aspiration biopsy (FNAB) is the preferred technique for the initial
      diagnostic evaluation of thyroid lesions, which nevertheless poses a diagnostic
      challenge for all clinicians involved. The latter necessitates the use of
      molecular markers on thyroid cytology. MIB-1 is a molecular marker already used
      in the cytological evaluation of various tumors. In this study, we assessed
      whether MIB-1 proliferation index adds diagnostic information to the conventional
      cytological analysis of thyroid nodules and prognostic information in thyroid
      cancers. MIB-1 index for various thyroid lesions was retrospectively reviewed in
      a series of 504 patients. Furthermore, the prognostic value of MIB-1 index was
      investigated for 183 of the patients with papillary thyroid cancer (PTC). MIB-1
      index was significantly higher in anaplastic thyroid cancer (ATC) compared to
      other tumor types (p<0.01). No significant difference in MIB-1 index was observed
      between thyroid adenomas and follicular carcinomas. In PTC, MIB-1 index equal to
      or >4% was found to be an independent factor significantly associated with higher
      risk of distant metastasis and disease-related mortality (p<0.05). Conclusively,
      this study shows that preoperative MIB-1 index assessment in FNAB of thyroid
      nodules offers little diagnostic information as far as follicular tumors are
      concerned. In cases of PTC, though, MIB-1 may serve as a prognostic indicator of
      disease spreading and poor survival and hence influence the planning of the
      overall treatment scheme.

PMID- 19578752
TI  - Small interference RNA-mediated suppression of overexpressed cyclin E protein
      restores G1/S regulation in NIH-OVCAR-3 ovarian cancer cells.
AB  - The development of ovarian cancer, unlike that of most human tumors, is rarely
      dependent upon the mutually exclusive loss of RB and p16 cell cycle proteins.
      RB+/p16+ ovarian cancer cell lines are, however, insensitive to the growth
      suppressive effects of ectopically expressed p16 protein, which suggests that
      they harbor as yet unidentified defects that compromise cell cycle regulation in
      late G1/S. In the current study, we used Western blotting to analyze cyclin E
      protein expression in a panel of normal and tumor ovarian tissues and ovarian
      cancer cell lines (including the p16-insensitive RB+/p16+ ovarian cancer cell
      line, NIH-OVCAR-3). Both the NIH-OVCAR-3 cell line and 70% of RB+/p16+ ovarian
      tumors showed abnormally elevated levels of the full-length cyclin E protein
      (EL1) in addition to several low molecular weight (LMW) isoforms of cyclin E.
      Using small interference RNA (siRNA), we have inhibited the synthesis of cyclin
      EL1 protein by approximately 80% and eliminated the LMW isoforms in NIH-OVCAR-3
      ovarian cancer cells. Associated with the down-regulation of cyclin E expression,
      we observed both a marked shift in RB protein expression to the active,
      hypophosphorylated state and barely detectable expression of cyclin A (which is
      usually expressed upon entry into S-phase). Consistent with the protein
      expression data, cell cycle distribution analysis indicated that the NIH-OVCAR-3
      cells had undergone a marked accumulation in G1 phase of the cell cycle. These
      data indicate the therapeutic potential of targeted RNA interference in the
      treatment of ovarian cancer patients whose tumors overexpress cyclin E protein.

PMID- 19578753
TI  - Molecular analysis of a collection of clinical specimens stored at 4 degrees C as
      an alternative to snap-freezing.
AB  - It is critical for both basic and clinical translational cancer research to use
      high quality DNA, RNA and proteins from specimens with clinical outcome in order
      to validate novel diagnostic biomarkers and to monitor successful treatments for
      patients. However, using current standard procedures, the collection of specimens
      is often limited by the availability of liquid nitrogen in some hospitals and
      liquid nitrogen can be hazardous to transport. These problems would be eased if
      the tissue could be stored unfixed at 4 degrees C, conditions that are readily
      available in hospitals. Thus the effect of storing tissue specimens at 4 degrees
      C on the quality of DNA, RNA and protein has been examined. Clinical tissue
      samples were halved and kept either at 4 degrees C for up to 24 h or snap-frozen
      in liquid nitrogen within 30 min of removal from the patient. The results show
      that the quality of RNA, DNA and protein isolated from the specimens stored at 4
      degrees C up to overnight is equal to that obtained from snap-frozen material. In
      conclusion, simplifying the collection procedure may allow for greater
      flexibility of conducting studies in units where liquid nitrogen is not readily
      available.

PMID- 19578754
TI  - CBP-mediated post-translational N-glycosylation of BRCA2.
AB  - CREB binding protein (CBP) is a transcriptional cofactor with intrinsic histone
      acetyl transferase activity (HAT). We have observed that CBP interacts with BRCA2
      and mediates post-translational glycosylation of BRCA2. The binding of CBP to the
      amino-terminal region of BRCA2 is necessary for the glycosylation at residue 272
      of BRCA2. Digestion with peptide N-glycosidase F indicates that the glycosylation
      of BRCA2 is N-linked. It is possible that this novel CBP-mediated post
      translational N-glycosylation activity alters the conformation of CBP-interacting
      proteins, leading to regulation of gene expression, cell growth and
      differentiation.

PMID- 19578755
TI  - Altered expression of selected microRNAs in melanoma: antiproliferative and
      proapoptotic activity of miRNA-155.
AB  - Altered expression of microRNAs (miRNAs) has been detected in cancer, suggesting
      that these small non-coding RNAs can act as oncogenes or tumor suppressor genes.
      In the present study, we investigated the expression of miRNA-17-5p, miRNA-18a,
      miRNA-20a, miRNA-92a, miRNA-146a, miRNA-146b and miRNA-155 by real-time
      quantitative RT-PCR in a panel of melanocyte cultures and melanoma cell lines and
      explored the possible role of miRNA-155 in melanoma cell proliferation and
      survival. The analyzed miRNAs were selected on the basis of previous studies
      strongly supporting their involvement in cancer development and/or progression.
      We found that miRNA-17-5p, miRNA-18a, miRNA-20a, and miRNA-92a were
      overexpressed, whereas miRNA-146a, miRNA-146b and miRNA-155 were down-regulated
      in the majority of melanoma cell lines with respect to melanocytes. Ectopic
      expression of miRNA-155 significantly inhibited proliferation in 12 of 13
      melanoma cell lines with reduced levels of this miRNA and induced apoptosis in 4
      out of 4 cell lines analyzed. In conclusion, our data further support the finding
      of altered miRNA expression in melanoma cells and establish for the first time
      that miRNA-155 is a negative regulator of melanoma cell proliferation and
      survival.

PMID- 19578756
TI  - Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated
      with p53-dependent and p53-independent responses.
AB  - Cisplatin is a first-line chemotherapeutic agent and a powerful component of
      standard treatment regimens for several human malignancies including bladder
      cancer. DNA-Pt adducts produced by cisplatin are mainly responsible for cellular
      toxicity and induction of apoptosis. Identification of the mechanisms that
      control sensitivity to cisplatin is central to improving its therapeutic index
      and to successfully encountering the acquired resistance frequently emerging
      during therapy. In the present study, using MTT-based assays, Western blotting
      and semi-quantitative RT-PCR, we examined the apoptosis-related cellular
      responses to cisplatin exposure in two human urinary bladder cancer cell lines
      characterized by different malignancy grade and p53 genetic status. Both RT4
      (grade I; wild-type p53) and T24 (grade III; mutant p53) cell types proved to be
      vulnerable to cisplatin apoptotic activity, albeit in a grade-dependent and drug
      dose-specific manner, as demonstrated by the proteolytic processing profiles of
      Caspase-8, Caspase-9, Caspase-3, and the Caspase repertoire characteristic
      substrates PARP and Lamin A/C, as well. The differential resistance of RT4 and
      T24 cells to cisplatin-induced apoptosis was associated with an RT4-specific
      phosphorylation (Ser15; Ser392) pattern of p53, together with structural
      amputations of the Akt and XIAP anti-apoptotic regulators. Furthermore, cisplatin
      administration resulted in a Granzyme B-mediated proteolytic cleavage of Hsp90
      molecular chaperone, exclusively occurring in RT4 cells. To generate functional
      networks, expression analysis of a number of genes, including Bik, Bim, Bcl-2,
      FAP-1, Fas, FasL, TRAIL, Puma, Caspase-10, ATP7A, ATP7B and MRP1, was performed,
      strongly supporting the role of p53-dependent and p53-independent transcriptional
      responses in cisplatin-induced apoptosis of bladder cancer cells.

PMID- 19578757
TI  - TCDD mediates inhibition of p53 and activation of ERalpha signaling in MCF-7
      cells at moderate hypoxic conditions.
AB  - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is known to promote cancer initiation
      and progression and accumulates in mammary fat tissue. Effects of TCDD are
      mediated by the aryl hydrocarbon receptor (AhR). Physiological conditions of
      moderate hypoxia in breast cancer also activate another transcription factor,
      hypoxia-inducible factor-1 alpha (HIF-1alpha). In addition, the transcription
      factors p53 and the estrogen receptor alpha (ERalpha) are important key players
      in breast cancer progression. Here, human breast cancer cells cultured under mild
      hypoxic conditions were exposed to TCDD and analyzed for regulation of p53
      signaling and ERalpha transactivation. Simultaneous exposure to TCDD and hypoxia
      resulted in a moderate but reproducible inhibition of p53 expression. Both the
      direct activation of the ERalpha and the transcriptional regulation of Hdm2
      mediated this inhibition. As consequence the p53-mediated target gene expression
      (Dusp5) was reduced. Silencing of Dusp5 by simultaneous exposure of TCDD and
      hypoxia or by RNAi led to increased phosphorylation of ERK1/2. This increase
      resulted in transactivation of ERalpha and induction of ERalpha-mediated
      transcription of Hdm2 and SOCS3. Specificity of ERalpha-transactivation by ERK1/2
      was confirmed by treatment with MAPKK-inhibitor PD98059. The combination of
      inhibition of functional p53 protein and induction of ERalpha signaling could
      serve as a model for the operational sequence of TCDD effects to prevent cell
      death and promote breast tumor progression.

PMID- 19578758
TI  - Suppression of cell invasiveness by periostin via TAB1/TAK1.
AB  - We have previously shown that the expression of periostin is significantly
      downregulated in human bladder cancer tissues and that periostin suppresses cell
      invasiveness and metastasis of cancer cells. To clarify the molecular mechanism
      of this suppression by periostin, we searched for periostin-binding proteins and
      identified TAB1, which interacts with and activates TAK1, by mass analysis of
      proteins co-precipitated with periostin in 293T cells expressing periostin. The
      association between periostin and TAB1 was confirmed by a pulldown assay in 293T
      cells co-tranfected with expression plasmids of periostin, TAB1 and TAK1. TAK1
      was also co-precipitated with periostin in this assay. Co-transfection
      experiments in 293T also showed that periostin could activate TAK1. Introduction
      of siRNA for TAB1 suppressed TAK1 activation by periostin. Analyses with deletion
      mutants of periostin revealed that the C-terminal region of periostin was
      necessary and sufficient for the association with TAB1 and the TAK1 activation.
      The suppression of invasiveness by periostin was attenuated by siRNA targeting
      TAK1 or TAB1 in 293T (human embryonic kidney) and T24 (human bladder carcinoma)
      cell lines. These findings indicate that periostin is involved in the suppression
      of cell invasiveness via the TAB1/TAK1 signaling pathway.

PMID- 19578760
TI  - Epigenetic alterations associated with cholangiocarcinoma (review).
AB  - Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the
      biliary tract epithelium. Chronic inflammatory conditions, including primary
      sclerosing cholangitis, liver fluke infestation, and hepatolithiasis, are
      considered risk factors, but the cause is still unknown in most cases. Recent
      advances in molecular pathogenesis have highlighted the importance of epigenetic
      alterations, including promoter hypermethylation and histone deacetylation, in
      the process of cholangiocarcinogenesis. More recently, research interest has been
      focusing on microRNA (mir), a major subtype of non-coding RNA. Mir is highly
      conserved among species and regulates the expression of specific target genes by
      binding to the 3'-untranslated regions of messenger RNA. The number of studies on
      a possible link between mir and various cancers is growing. This review provides
      a comprehensive overview of the genes currently known to be hypermethylated in
      CCA and their putative roles in cholangiocarcinogenesis. The epigenetic role of
      mir in the pathogenesis of CCA is also discussed.

PMID- 19578761
TI  - Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the
      ovary (review).
AB  - Epithelial ovarian cancer (EOC) is the leading cause of death in women with
      gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and
      endometrioid adenocarcinoma (EAC) differ from the other histological types with
      respect to their clinical characteristics and carcinogenesis. Both tumor types
      are often associated with endometriosis. EAC is recently reported to be
      characterized by K-RAS activation and PTEN dysfunction. However, the molecular
      changes in CCC remain largely unknown. The aim of this review is to summarize the
      current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The
      present article reviews the English language literature for biological,
      pathogenetic and pathophysiological studies on endometriosis-associated CCC of
      the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss,
      comparative genomic hybridization, mutation, methylation status, microarray gene
      expression profiling and proteomics are discussed in the context of CCC biology.
      Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors,
      such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A
      histologically normal ectopic endometrium bears genetic damages caused by iron
      dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a
      critical factor in the carcinogenic process. LOH studies have implicated the
      involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q).
      Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K
      RAS (late event) genes may be involved in CCC carcinogenesis. The molecular
      pathology of CCC is heterogeneous and involves various putative precursor lesions
      and multiple pathways of development, possibly via genetic alteration by
      oxidative stress.

PMID- 19578762
TI  - Antitumor activity of bevacizumab in combination with capecitabine and
      oxaliplatin in human colorectal cancer xenograft models.
AB  - To understand the mechanisms of the effects of combination treatments, we
      established animal models showing antitumor activity of bevacizumab as a
      monotherapy and in combination with capecitabine or capecitabine and oxaliplatin
      and measured thymidine phosphorylase (TP) and vascular endothelial growth factor
      (VEGF) levels. Tumor-inoculated nude mice were treated with bevacizumab,
      capecitabine, and oxaliplatin, alone or in combination, after tumor growth was
      confirmed and volume and microvessel density (MVD) in tumors were evaluated.
      Levels of TP and VEGF in the tumor were examined by ELISA. Bevacizumab showed
      significant antitumor activity as a monotherapy in three xenograft models (COL-16
      JCK, COLO 205 and CXF280). The MVD in tumor tissues treated with bevacizumab was
      lower than that of the control. Antitumor activity of bevacizumab in combination
      with capecitabine was significantly higher than that of each agent alone (COL-16
      JCK, COLO 205). Furthermore, the antitumor activity of bevacizumab in combination
      with capecitabine + oxaliplatin was significantly superior to that of
      capecitabine + oxaliplatin (COL-16-JCK). TP and VEGF levels were not increased by
      bevacizumab or capecitabine, respectively, suggesting there are other potentially
      efficacious mechanisms involved. In the present study we established human
      colorectal cancer xenograft models which reflect the efficacy of clinical
      combination therapies, capecitabine + bevacizumab and capecitabine + oxaliplatin
      + bevacizumab. We will further investigate the mechanisms of the combination
      therapies using these models.

PMID- 19578763
TI  - hnRNP U interacts with the c-Myc-Max complex on the E-box promoter region
      inducing the ornithine decarboxylase gene.
AB  - The promoter of the ornithine decarboxylase (ODC) gene contains two E-boxes,
      which are critical sites for transcriptional activation by the binding of c-Myc
      Max heterodimers. We have identified heterogeneous nuclear ribonuclear protein U
      (hnRNP U) as a component of the complex formed on the E-box-containing promoter
      region of the ODC gene by using DNA-affinity chromatography, immunoprecipitation
      and chromatin immunoprecipitation assays. The N-terminal domain of hnRNP U was
      responsible for the association with c-Myc-Max complex. Down-regulation of hnRNP
      U with RNA interference blocked the induction of the ODC gene and cell growth by
      serum stimulation, suggesting that hnRNP U is a coactivator of the c-Myc-Max
      complex and essential for cell proliferation. Electrophoretic mobility-shift
      assays revealed that the segment between the two E-boxes in the promoter is the
      primary binding site of hnRNP U. The putative binding sequence was narrowed-down
      to a 13-nucleotide segment by comparing the sequence between the E-boxes with the
      binding sites of hnRNP U, which were recently identified in the promoter of
      Bmal1, a core component of the circadian molecular oscillator. These findings
      increase our knowledge of how the c-Myc-Max complex exerts its transcriptional
      regulatory role and suggest that hnRNP U may be a coactivator of this
      transcriptional activator complex.

PMID- 19578764
TI  - Proliferation of estrogen-responsive mouse tumor cell line B-1F stimulated by
      Saiboku-to, but inhibited by Scutellaria baicalensis, a component of Saiboku-to.
AB  - We have demonstrated that the proliferation of estrogen-responsive mouse Leydig
      tumor cell line B-1F is induced via suppression of 5-lipoxygenase activity
      followed by decrease of leukotrienes (LTs). Additionally, it has been reported
      that LTD4 induces apoptosis in B-1F cells. In this study, we examined effects of
      Saiboku-to, a traditional Chinese medicine having suppressive activities for LT
      production and release, on the proliferation. Saiboku-to promoted, but
      Scutellaria baicalensis, one of components (herbs) of Saiboku-to, significantly
      inhibited the proliferation of B-1F cells in vitro and in vivo. The action of
      Scutellaria baicalensis in B-1F cells was studied in more detail. Although
      Scutellaria baicalensis consists of flavonoids, iridoids, volatile oils and
      others, it and its major constituents had no direct effect on estrogen binding
      sites in B-1F cells. B-1F cells treated with Scutellaria baicalensis showed
      morphological changes such as nuclear aggregation and fragmentation. DNA
      fragmentation was also observed, indicating that Scutellaria baicalensis induces
      apoptosis in B-1F cells and that it or its constituents might be a good resource
      for searching new drugs, especially anti-cancer drugs. Moreover, Saiboku-to
      promoted B-1F cell proliferation, but Scutellaria baicalensis inhibited it,
      showing complexity of action of traditional Chinese medicines.

PMID- 19578765
TI  - Differences in expression between transcripts using alternative promoters of
      hMLH1 gene and their correlation with microsatellite instability.
AB  - hMLH1 is involved in DNA mismatch repair and its defects cause hereditary non
      polyposis colorectal cancer (HNPCC) as well as other types of cancer. A defective
      DNA mismatch repair system results in genetic instability, also referred to as
      microsatellite instability (MSI), which is a good indicator of HNPCC. Using in
      silico analysis of oligo-capping cDNA sequences, we initially identified a
      splicing (variant type 2) whose second exon is 5 bp shorter than that of a
      genuine hMLH1 transcript (variant type 1) and a transcript using alternative
      promoter (variant type 3) whose transcription starts about 300 bases downstream
      of variant type 1. We then compared the expression level of variant types 1 and 3
      among six colorectal cancer cell lines using real-time PCR. As a result, we found
      that the cell lines that completely suppress the expression of variant type 1 by
      hypermethylation expressed variant type 3 to a certain extent. This result
      suggests that the expression of variant types 1 and 3 did not completely follow
      the same transcription mechanism. We also found that the cell lines showing MSI
      to be positive either expressed variant type 3 more than type 1 or expressed only
      variant type 3. These results showed the potential applicability of mRNA
      expression analysis to molecular diagnostic tests of MSI-positive cancer types.

PMID- 19578766
TI  - A low number of tumor-infiltrating FOXP3-positive cells during primary systemic
      chemotherapy correlates with favorable anti-tumor response in patients with
      breast cancer.
AB  - Cancer cells induce proliferation and local accumulation of immunosuppressive
      cells, such as FOXP3-positive cells known as regulatory T cells (Tregs), leading
      to tumor-induced immune tolerance. Although cancer chemotherapy is usually
      considered immunosuppressive, some chemotherapeutic agents activate an anticancer
      immune response. Therefore, we postulated that the number of tumor-infiltrating
      FOXP3-positive cells during primary systemic chemotherapy (PSC) correlates with
      therapeutic outcomes in patients with breast cancer. Between September 2000 and
      January 2005, we examined 93 patients with breast cancer diagnosed by core-needle
      biopsy and treated with PSC. Core-needle biopsy (CNB) and surgical resected
      specimens were stained with a FOXP3 mouse monoclonal antibody to compare the
      numbers of FOXP3-positive cells in the tumors before and after PSC. A median cut
      off value of >16.3/high power field (HPF) and >6.6/HPF defined high numbers of
      Tregs in CNB and in surgical specimens, respectively. We then assigned the
      patients into 4 groups (HH, high number of FOXP3-positive cells in both CNB and
      surgical specimen; LL, low number in both specimens; HL, high in CNB and low in
      the surgical specimen; LH, low in CNB and high in surgical specimen). Lymph
      vessel invasion-positive, clinically non-responder and ER-negative tumors
      contained significantly more FOXP3-positive cells after PSC (p=0.04, p=0.03 and
      p=0.04, respectively). Prognosis was better among patients with low numbers than
      high numbers of FOXP3-positive cells both in CNB and in surgically resected
      specimens. In multivariate analysis, LL group demonstrated significantly better
      recurrence-free survival with risk ratio of 5.81 (95%CI, 1.09-107.5; p=0.04)
      rather than that of non-LL group (LH, HL and HH). These findings suggest that the
      number of FOXP3-positive cells identified during PSC represents a promising
      predictive factor that might also be an important therapeutic target for breast
      cancer.

PMID- 19578767
TI  - Cancerous, but not stromal, thrombospondin-2 contributes prognosis in pulmonary
      adenocarcinoma.
AB  - Thrombospondin (TSP)-2 is known to be an endogenous negative regulator of
      vascularization in human cancer. However, it is unclear whether TSP-2 expression
      is related to neovascularization and prognosis in non-small cell lung cancer. In
      this study, we quantitatively examined the expression of TSP-2 mRNA by real-time
      reverse transcription-polymerase chain reaction (RT-PCR) in 102 pulmonary
      adenocarcinomas. All 102 carcinoma specimens expressed TSP-2 mRNA. The expression
      of TSP-2 mRNA in carcinoma was significantly higher than normal lung tissues
      (p<0.0001, Kruskal-Wallis test). Sizes of tumors were significantly correlated
      with TSP-2 gene expression (p=0.0179, Kruskal-Wallis test). The TSP-2 expression
      levels of the stage II/III pulmonary carcinomas were significantly increased as
      compared to those of stage I (p=0.0136, Kruskal-Wallis test). Thirty-five
      patients with high TSP-2 mRNA expression showed poor prognosis in survival
      (p=0.0139, log-rank test). We examined TSP-2 protein localizations in the
      pulmonary adenocarcinoma overexpressing TSP-2 mRNA. The TSP-2 localizations were
      categorized in two patterns: cancerous TSP-2 expression pattern (TSP-2 expression
      in the cancerous cells) and non-cancerous TSP-2 expression pattern (TSP-2
      expression in the stromal lymphoid cells). Pulmonary adenocarcinoma patients with
      cancerous TSP-2 expression pattern showed good prognosis (p=0.0322; Fisher's
      probability exact test). Pulmonary adenocarcinoma patients with non-cancerous TSP
      2 expression pattern showed poor prognosis (p=0.0220; Fisher's probability exact
      test). Non-cancerous TSP-2 expressions may reflect secondary reactions in the
      cancerous stroma. The stromal TSP-2 expression is not enough to suppress growth
      of pulmonary adenocarcinoma, while the cancerous TSP-2 expression directly
      inhibits growth of the carcinoma.

PMID- 19578768
TI  - Angiogenesis in cervical cancer is mediated by HeLa metabolites through
      endothelial cell tissue kallikrein.
AB  - High vascularity correlates with poor clinical outcome in cancer of the uterine
      cervix. We investigated whether human cervical cancer cell (HeLa) metabolites
      influenced endothelial cell proliferation through the serine protease, tissue
      kallikrein. The angiogenic potential of tissue kallikrein is proposed due to its
      proteolytic, mitogenic and invasive properties. Under pre-defined conditions, we
      examined the regulation of tissue kallikrein simultaneously in both endothelial
      and HeLa cells using immunochemistry, ELISA, cell proliferation assays and in
      situ RT-PCR. In an endothelial-cervical carcinoma conditioned-medium model, HeLa
      metabolites caused a dramatic decrease in endothelial cellular tissue kallikrein
      and a concomitant proliferation of endothelial cells. ELISA on the conditioned
      media showed a dose-dependent increase of tissue kallikrein, while in situ RT-PCR
      demonstrated no change in tissue kallikrein mRNA in both endothelial and HeLa
      cells when challenged with each other's metabolites. This demonstration of the
      ability of cervical cancer to simultaneously manipulate both tissue kallikrein
      processing within endothelial cells and angiogenesis is novel. Should this occur
      in vivo, the tissue kallikrein released from the endothelial cells into the
      microenvironment may simultaneously degrade the matrix and elicit a mitogenic
      effect by promoting angiogenesis. Pre-treatment with TK inhibitors and/or anti
      angiogenic therapies may prove to benefit future cervical cancer patients.

PMID- 19578769
TI  - Immunoexpression of inhibitors of apoptosis proteins and their antagonist
      SMAC/DIABLO in colorectal carcinoma: correlation with apoptotic index, cellular
      proliferation and prognosis.
AB  - The inhibitors of apoptosis proteins (IAPs) act by directly blocking cleaved
      caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of
      XIAP activity or the increase of SMAC activity might improve the therapeutic
      response of the patients. This work evaluated the immunoexpression of IAPs and
      SMAC in colorectal carcinoma and their correlation with apoptotic index (AI),
      cellular proliferation, p53 protein immunoexpression and patient survival rate.
      TMA paraffin blocks were made with colorectal cancer tissue and adjacent non
      tumorous mucosa of 130 patients, not submitted to radio or chemotherapy. Sections
      of 4 microm were processed by immunohistochemistry for survivin, XIAP, cIAP-1,
      cIAP-2 and SMAC, and the immunoexpression scores were obtained. They were
      correlated between each other and with the AI obtained by anti-cleaved caspase-3
      and M30 (cleaved cytokeratin-18) antibodies, the cellular proliferation index,
      p53 protein immunoexpression and patient survival data. Direct correlation
      occurred between the four IAPs studied in tumor and non-tumorous mucosa tissues.
      SMAC, survivin, cIAP-1 and cIAP-2 were positively correlated with tumoral tissue
      AI. Cellular proliferation and p53 immunoexpression was positively correlated
      with XIAP, SMAC and cIAP-1 scores. Low cIAP-1 immunoexpression showed a tendency
      for correlation with shorter patient survival. Equilibrium between the activities
      of IAPs and SMAC was demonstrated by the direct correlation between their
      immunoexpression. Correlation between SMAC and AI confirmed the pro-apoptotic
      activity of this protein. XIAP showed no inverse correlation with AI. XIAP, SMAC
      and cIAP-1 play a role in colorectal tumorigenesis, as demonstrated by their
      direct correlation with cellular proliferation and p53 protein. The tendency for
      correlation between low cIAP-1 immunoexpression and survival might indicate a
      role for this protein as a prognostic marker in colorectal cancer.

PMID- 19578770
TI  - Chromosomal imbalances, 11q21 rearrangement and MECT1-MAML2 fusion transcript in
      mucoepidermoid carcinomas of the salivary gland.
AB  - The aim of this study was to determine genetic alterations in mucoepidermoid
      carcinomas of the salivary gland in association with clinical and
      histopathological parameters. Nineteen formalin-fixed, paraffin-embedded tumors
      were analysed by using comparative genomic hybridization (CGH), fluorescence in
      situ hybridization (FISH) on interphase nuclei and reverse transcriptase
      polymerase chain reaction (RT-PCR) for detection of MECT1-MAML2 fusion
      transcript. The CGH analysis showed an overrepresentation of chromosome X and
      losses of entire chromosomes or regions on chromosome 1, 2, and 15 as the most
      frequent copy number changes. In 37% of the analysed tumors a MAML2-rearrangement
      by interphase FISH was detected, whereas 58% of the samples showed expression of
      MECT1-MAML2 fusion transcript. We conclude that the presence of MAML2
      rearrangement as well as of MECT1-MAML2 fusion transcript may reflect a more
      favourable prognosis and may be a useful marker for clinical prediction of the
      biological behavior of these tumors as previously reported.

PMID- 19578771
TI  - The regulatory effect of the p38 signaling pathway on valdecoxib-induced
      apoptosis of the Eca109 cell line.
AB  - Valdecoxib is a second generation selective COX-2 inhibitor that can induce cell
      apoptosis in a variety of cell types, but its precise regulatory mechanism is
      unknown. Apoptosis of Eca109 cells and p38 mRNA expression were investigted. The
      expression of p-p38MAPK, Fas and FasL proteins were detected by
      immunohistochemical staining and FCM. Valdecoxib increased the apoptosis rate of
      Eca109 cells. Fas and FasL protein expression was up-regulated in the valdecoxib
      groups, while SB203580 partly inhibited the valdecoxib-induced overexpression.
      Valdecoxib increased p38MAPK expression, while SB203580 inhibited the
      overexpression of this protein and the apoptosis rate decreased. The expression
      of Fas, FasL and p38MAPK protein were positively correlated with the apoptotic
      rate. In conclusion, valdecoxib activates the p38MAPK pathway, thus up-regulating
      expression of the Fas and FasL proteins, which may be one of the mechanisms
      through which valdecoxib induces apoptosis.

PMID- 19578772
TI  - Paclitaxel encapsulated in cationic liposomes: a new option for neovascular
      targeting for the treatment of prostate cancer.
AB  - Neovascular targeting is an established approach for the therapy of prostate
      cancer (PCa). Cationic liposomes have been shown to be absorbed by immature
      vascular endothelial cells due to negative electric charge of their outer cell
      membrane. We aimed to evaluate the antitumoural efficacy of paclitaxel
      encapsulated in cationic liposomes for the treatment of PCa. Tumours were
      generated by subcutaneous injection of 10(6) MatLu tumour cells into the right
      hind leg of 21 male Copenhagen rats. After tumour growth, the animals were
      treated by an i.v. infusion with either 5% glucose (Gl), paclitaxel (Pax),
      cationic liposomes (CL) or paclitaxel encapsulated in cationic liposomes (EndoTAG
      1) on days 12, 14, 16 and 19. Treatment was initiated on day 12 after tumour
      inoculation at mean tumour volumes of 0.31+/-0.13 mm(3). On the last day of
      treatment, animals treated with EndoTAG-1 had the significantly lowest tumour
      volumes with 2.49+/-0.84 cm(3) vs. Pax (5.59+/-0.45 cm(3)) vs. CL (3.87+/-1.25
      cm(3)) vs. GL (5.17+/-1.70 cm(3)). The quantification of MVD showed the lowest
      count for EndoTAG-1-treated tumours (11.78+/-2.68 vessels/mm(2)) followed by Gl
      (15.64+/-6.68 vessels/mm(3)), Pax (18.22+/-9.50 vessels/mm(3)) and CL (40.9+/
      32.8 vessels/mm(3)). The data confirm that neovascular targeting with EndoTAG-1
      is a promising new method for the treatment of PCa by reducing the primary tumour
      mass and demonstrating benefits in the suppression of angiogenesis in comparison
      with the conventional treatment.

PMID- 19578773
TI  - Androgen deprivation therapy regulation of beta1C integrin expression in prostate
      cancer.
AB  - The beta1C integrin is an alternatively spliced variant of the beta1 integrin
      subfamily that at variance with its wild-type counterpart, i.e., the beta1A
      integrin, inhibits cell proliferation in prostate cancer cells. We have recently
      shown that transcriptional, translational and post-translational processes
      contribute to the selective loss of beta1C integrin during prostate malignant
      transformation. Here, we investigated whether androgen deprivation therapy (ADT)
      may affect beta1C mRNA expression in prostate cancer. Neoplastic prostates were
      obtained from patients undergoing radical prostatectomy who had received
      neoadjuvant ADT. The beta1C mRNA level was measured by Northern hybridization
      experiments and compared to normal prostates obtained from patients who underwent
      radical cystoprostatectomy for bladder cancer. Furthermore, the beta1C integrin
      gene transcriptional activity was measured by nuclear Run-on assays. We found an
      increase of beta1C mRNA expression (208+/-11%; p<0.01) in patients who received
      ADT in comparison to those who did not. Furthermore, we demonstrated an increase
      of gene transcriptional activity (360+/-10%; p<0.01) possibly partially or
      completely responsible for the regulation of the beta1C integrin mRNA levels.
      Short-term administration of ADT seems to interfere with beta1C integrin
      expression, suggesting the existence of androgen-mediated pathways involving
      beta1C. Precise characterization of the mechanisms that regulate the expression
      of this factor in cancer cells will provide further insight into the molecular
      mechanisms involved in tumor progression and possibly contribute to the
      identification of molecular targets for the development of new therapeutic
      strategies.

PMID- 19578774
TI  - Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a
      combination of dendritic cell fusion hybrids and regulatory T cell depletion in
      pancreatic cancer.
AB  - Regulatory T cells (Tregs) play an important role in immunological self-tolerance
      and protect the host from autoimmune disease. However, in cancer immunity, Tregs
      might block anti-tumor immune responses. Therefore, the depletion of Tregs using
      a specific agent that suppresses its function or population, such as an anti-CD25
      antibody, could promote anti-tumor immune responses. In the present study, a
      cytotoxicity assay, enzyme-linked immunosorbent spot (ELISPOT) assay and
      measuring cytokine secretion, were used to study the efficacy of Treg depletion
      by anti-CD25 antibody added to a dendritic cell/tumor cell (DC/TC) fusion hybrid
      vaccine in a murine pancreatic cancer model. All the mice treated with the
      combined therapy of fusion hybrid vaccine and Treg depletion rejected tumor
      growth in a challenging test, although the rejection rate was 20% both for mice
      that received the fusion hybrids alone or Treg depletion alone. In addition,
      combined therapy showed a significantly improved survival in comparison to other
      treatment or control groups. The NK cell activity for DC/TC fusion + Treg
      depletion was significantly higher than that for the other treatment groups.
      Cytotoxic T lymphocyte (CTL) activity for DC/TC could potentially be enhanced by
      the addition of Treg depletion therapy. The treatments including DC/TC fusion
      induced IFN-gamma secreting effector cells in ELISPOT assays. Furthermore, a
      cytometric beads array assay used to measure cytokine secretion showed that DC/TC
      fusion + Treg depletion stimulated the highest levels of IFN-gamma Th1/Th2 ratios
      and Th17. These results demonstrate that Treg depletion combined with DC/TC
      fusion hybrid vaccine enhanced the efficacy of immunotherapy in pancreatic cancer
      by activating CTLs and NK cells.

PMID- 19578775
TI  - Survival after cytotoxic chemotherapy in patients with advanced hormone-resistant
      prostate cancer: a phase II study.
AB  - In the past, it was believed that when advanced-stage prostate cancer became
      resistant to hormonal management, no chemotherapy should be administered, as
      survival was not prolonged. Mitoxanthrone and prednisone were mostly
      administered, while recently, other agents such as docetaxel or paclitaxel have
      been tested both with and without hormonal treatment. The objective of the
      present phase II study was to determine the survival and the response rate of
      patients after the chemotherapy was administered. Sixty-five patients with
      advanced prostate cancer were included. The inclusion criteria involved
      histological confirmation of adenocarcinoma and resistance to hormonal therapy.
      The majority of the patients had stage IVa or IVb disease and a performance
      status of 0-1 to 2. The treatment involved chemotherapy in combination with a
      luteinizing hormone-releasing hormone (LHRH) or dexamethasone or estramustine.
      The hormone treatment preceded the cytotoxic administration and no amelioration
      in the patients nor prostate serum antigen (PSA) reduction was observed. The
      initial cytotoxic agents administered were docetaxel 75 mg/m(2) in 25 patients,
      mitoxanthrone 10 mg/m(2) in 15 patients, epirubicin 75 mg/m(2) in 15 patients and
      paclitaxel 175 mg/m(2) in 10 patients, all repeated every 3 weeks. The response
      rate was documented by bone scan, CT scan of the abdomen (and occasionally of the
      chest) and by the PSA serum value. Clinical benefit was also estimated. Thirty
      three (50.77%) patients achieved a partial response; stable disease was observed
      in 24 (36.92%) patients and disease progression in 8 (12.31%). Twenty-two
      (33.85%) experienced clinical benefit. A significant PSA reduction was seen in 35
      (53.85%) patients. The median survival was 18 months and the range 3-84 months.
      One, 2, 3 and five-year survival was 75.38, 23.07, 12.30 and 4.66%, respectively.
      Toxicity was well-tolerated. Patients with hormone-resistant advanced prostate
      cancer do have good prospects for receiving substantial benefit with the addition
      of chemotherapy, as observed in the present trial.

PMID- 19578776
TI  - Growth inhibitory activity of ethanol extracts of Chinese and Brazilian propolis
      in four human colon carcinoma cell lines.
AB  - More than 300 bio-active compounds have been identified from bee propolis in
      various regions of the world. The objective of this study was to examine whether
      the ethanol extracts of Chinese and Brazilian propolis may exert anticancer
      activities in four human colon carcinoma cell lines, namely CaCo2, HCT116, HT29
      and SW480. Propolis samples were extracted with ethanol, and the crude extracts
      were dissolved in dimethylsulfoxide and used for the experiments. In HCT116, HT29
      and SW480 cell lines, the extracts of both Chinese and Brazilian propolis caused
      a marked dose-dependent growth inhibition, with IC50 values in the range of 4-41
      microg/ml. In HCT116 cell line, Chinese propolis extract induced apoptosis in the
      cells after 72 h of treatment. In addition, Chinese propolis extract caused a
      dose-dependent increase in the cellular mRNA levels of p21CIP1 and p53 in the
      HCT116 cell line. These findings indicate that the ethanol extracts of propolis
      contain components that may have anticancer activity. Thus, propolis and related
      products may provide a novel approach to the chemoprevention and treatment of
      human colon carcinoma.

PMID- 19578777
TI  - Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor
      blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic
      activities.
AB  - Pancreatic cancer is one of the leading causes of cancer death, and represents a
      challenging chemotherapeutic problem. The crucial role of angiogenesis in tumor
      growth has been widely recognized, and several reports have revealed that the
      combination treatment of the conventional chemotherapeutic drugs and anti
      angiogenic agents exerted synergistic anti-cancerous effects. It has been
      reported that the clinically used angiotensin type-1 receptor blocker (ARB)
      exerted potent anti-angiogenic activity. The aim of our current study was to
      examine the combination effect of gemcitabine (GEM), a widely used conventional
      chemotherapeutic drug against pancreas cancer, and losartan (Lo), an ARB, on
      murine pancreatic tumor growth, especially in conjunction with angiogenesis. When
      used individually, GEM and Lo at clinically comparable low doses moderately
      suppressed pancreatic tumor development. The combination treatment with GEM and
      Lo exerted a marked inhibitory effect as compared with single agent treatments
      even after the tumor was fully established. Neovascularization and the expression
      of the vascular endothelial growth factor (VEGF), a central angiogenic factor, in
      the tumor were both markedly suppressed in a magnitude similar to the inhibitory
      effects against the tumor growth. Since both agents are widely used in the
      clinical practice, the combination regimen of GEM and Lo may represent a
      potential new therapeutic strategy for pancreatic cancer in the future.

PMID- 19578778
TI  - Tubulin inhibitor AEZS 112 inhibits the growth of experimental human ovarian and
      endometrial cancers irrespective of caspase inhibition.
AB  - AEZS 112 is an orally active small molecule anticancer drug which inhibits the
      polymerization of tubulin at low micromolar concentrations. The current study
      investigates the anti-tumor effect and the mechanism of action of AEZS 112 in in
      vitro models of human ovarian and endometrial cancers. Four human ovarian and 2
      endometrial cancer cell lines were incubated with increasing concentrations of
      AEZS 112 with and without multi-caspase inhibitor zVAD-FMK for 72 hours.
      Cytotoxic effects of AEZS 112 were analyzed using crystal violet staining, FACS
      analysis of DNA content as well as Annexin V/propidium iodide-double staining.
      AEZS 112 displayed anti-tumor activity in all six cell lines. The EC50 determined
      after 72-h incubation for Ishikawa and HEC 1A was 0.0312 and 0.125 microm,
      respectively. The EC50 was 5 microm for SKOV 3 cells, 1 microm for 0.5 microm for
      OAW 42 cells, 0.125 microm for OvW 1 cells and 0.0312 microm for PA 1 cells.
      Cytotoxic effects of AEZS 112 could not be abrogated by caspase inhibition with
      pan-caspase inhibitor zVAD-fmk. Annexin V/propidium iodide-double staining after
      treatment with AEZS 112 was indicative of necrosis-like cell death. AEZS 112 dose
      dependently increased non-vital hypodiploid cells and the cytotoxic effect was
      least pronounced in G2 phase of the cell cycle, indicating cell death during
      mitosis, as determined by FACS analysis. The orally active small molecule tubulin
      inhibitor AEZS 112 showed anti-tumor activity in human ovarian and endometrial
      cancer cell lines at low micromolar concentrations, which could not be abrogated
      by caspase inhibition and is therefore a good candidate for in vivo studies in
      these tumors.

PMID- 19578779
TI  - Alterations of glycosaminoglycan disaccharide content and composition in
      colorectal cancer: structural and expressional studies.
AB  - The glycosaminoglycans are implicated in many processes important in the growth
      and progression of malignant tumors. In the present study glycosaminoglycans were
      purified from healthy, macroscopically normal and cancerous specimens of
      different anatomic sites and different stages of cancer and analyzed by FACE
      after chondroitinases and sulfatases digestion. The cancerous samples contained
      increased levels of 6-sulfated unsaturated disaccharides compared to
      macroscopically normal and healthy samples, the increase being stage-related. The
      differences in sulfation were found to be related to the anatomic site and the
      stage of cancer. RT-PCR analysis of 4-sulfotransferase mRNA revealed its presence
      in decreasing amounts as the stage of the cancer increased. Furthermore, the
      percent content of hyaluronan disaccharides was elevated in macroscopically
      normal samples compared to the cancerous, and in addition, it was much more
      elevated than that of healthy samples. Haluronan levels increase with stage in
      cancerous tissues. Therefore, it could be concluded that the glycosaminoglycans
      in colorectal cancer are biosynthetically directed to contribute in different
      ways depending on the cancer stage and anatomical site.

PMID- 19578780
TI  - Serenoa repens induces growth arrest and apoptosis of human multiple myeloma
      cells via inactivation of STAT 3 signaling.
AB  - Serenoa repens, a palm species native to the Southeastern United States, is one
      of the widely used phytotherapeutic agents in benign prostatic hyperplasia. In
      this study, we found for the first time that Serenoa repens induced growth arrest
      of a variety of human leukemia cells including U266 and RPMI 8226 multiple
      myeloma cells as measured by mitochondrial-dependent conversion of the 3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. TUNEL assays showed
      that Serenoa repens induced apoptosis of U266 cells in a time- and dose-dependent
      manner. Serenoa repens also increased the expression of cleaved-PARP or p27
      protein in different human leukemia cell lines. In addition, we found that
      Serenoa repens down-regulated basal level of phosphorylated form of signal
      transducer and activator of transcription 3 (STAT 3) and Interleukin-6 induced
      level of phosphorylated form of STAT 3 and extracellular signal-related kinase
      (ERK) were also reduced after Serenoa repens treatment in U266 cells.
      Furthermore, we found that inhibition of STAT 3 signaling by Serenoa repens or
      Janus family of tyrosine kinase (JAK) inhibitor of AG490 enhanced the ability of
      docetaxel to inhibit the growth of U266 and RPMI 8226 cells, as measured by
      trypan blue exclusion test. These results indicate that Serenoa repens might be
      useful for the treatment of individuals with multiple myeloma.

PMID- 19578781
TI  - The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate
      or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to
      cell growth, reactive oxygen species and glutathione.
AB  - Antimycin A (AMA) inhibits mitochondrial electron transport between cytochrome b
      and c. We recently demonstrated that AMA inhibits the growth of lung cancer Calu
      6 cells and the changes of reactive oxygen species (ROS) and glutathione (GSH)
      levels affect apoptosis in Calu-6 cells. Here, we examined the effects of N
      acetyl-cysteine (NAC, a well known antioxidant), L-buthionine sulfoximine (BSO,
      an inhibitor of GSH synthesis), diethyl-dithiocarbamate (DDC, an inhibitor of Cu,
      Zn-SOD) or 3-amino-1,2,4-triazole (AT, an inhibitor of catalase) on AMA-treated
      Calu-6 cells in relation to cell death, ROS and GSH levels. Treatment with AMA
      induced cell growth inhibition, apoptosis and the loss of mitochondrial membrane
      potential (MMP) (DeltaPsim) in Calu-6 cells. While the intracellular ROS level
      was decreased in 50 microM AMA-treated Calu-6 cells, O2.- levels among ROS were
      significantly increased. AMA also induced GSH depletion in Calu-6 cells.
      Treatment with NAC showed decreasing effect on O2.- levels in AMA-treated cells
      preventing apoptosis, MMP (DeltaPsim) loss and GSH depletion in these cells. BSO
      significantly increased GSH depletion and apoptosis in AMA-treated cells. While
      both DDC and AT increased ROS levels in AMA-treated Calu-6 cells, only DDC
      intensified GSH depletion and apoptosis. BSO and AT increased the ROS level in
      Calu-6 control cells, but these agents did not induce apoptosis and GSH
      depletion. In conclusion, our results suggest that GSH depletion rather than ROS
      level in AMA-treated Calu-6 cells is more tightly related to apoptosis.

PMID- 19578782
TI  - Small polydispersed circular DNA contains strains of mobile genetic elements and
      occurs more frequently in permanent cell lines of malignant tumors than in normal
      lymphocytes.
AB  - Small polydispersed circular DNA (spcDNA) belongs to the extrachromosomal pool of
      DNA and is composed of heterogeneous DNA circles. Whether spcDNA has a special
      function is currently unclear but their occurrence was suggested to be linked to
      genetic instability. In this study we investigated as to whether human
      lymphocytes from healthy volunteers also harbour spcDNA and whether spcDNA is
      present in all permanent cell lines from human normal and malignant tissues.
      Moreover, we were interested to see whether spcDNA contains sequences of mobile
      genetic elements. Our results show that spcDNA is present in all samples
      investigated yet the amount is lower in normal lymphocytes when compared to
      cancer cell lines (5.4 vs. 17.8%). Alu sequences were present in 12/16 cancer
      cell lines whereas LINE-1 (L1) sequences were present in 15 of them. Six tumor
      cell lines also contained telomeric sequences. In contrast to that, spcDNA of
      normal lymphocytes contains Alu and L1 sequences only in 3/16 cases and no
      telomeric sequences at all. Our findings suggest a direct dependency of the
      amount of Alu and L1 sequences on that of spcDNA. Beside these repetitive
      sequences, sequencing of spcDNA revealed in most cases chromosomal sequences of
      almost all chromosomes without an increased frequency of single regions. We
      suggest that the whole spcDNA including retrotranspositional elements and
      telomeric sequences may play a role for chromosomal rearrangements and genomic
      instability.

PMID- 19578783
TI  - Identification of two new serum protein profiles for renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most lethal urological cancer, and survival
      greatly depends on early diagnosis. Therefore, reliable, new biomarkers for
      detection of RCC are required. We assessed serum protein profiles of samples from
      two institutes with SELDI-TOF MS in duplicate on CM10 chips at pH 6.0 (set 1: 37
      RCC + 32 healthy controls (HC), set 2: 20 RCC + 25 HC). Mean peak intensities of
      detected proteins were compared between RCC and HC with non-parametric testing.
      Classification trees were built with discriminating peaks using one sample set as
      training set and the other as independent validation set. We found 15 peaks
      significantly different (p<0.01) between RCC and HC. Two classification trees
      could be built with these peaks. Tree A achieved 75% sensitivity and 85%
      specificity for cross-validation and 76 and 65% for independent validation. Tree
      B had 71 and 62% sensitivity and specificity for cross-validation and 83 and 82%
      for independent validation. Although two serum protein profiles comprising 5
      protein peaks were found that could separate RCC from HC, the sensitivity and
      specificity is not sufficient to recommend large scale use. Upon structural
      identification and quantitative validation, however, these proteins might prove
      suitable markers in the follow up of RCC patients.

PMID- 19578784
TI  - Divergent effects of taurolidine as potential anti-neoplastic agent: inhibition
      of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo.
AB  - We investigated taurolidine (TRD) against various human bladder cell lines and
      the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in
      ascending concentrations depending on different incubation times on cell
      proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested
      cell lines. Increasing concentrations and longer incubation times decreased the
      proliferation depending on the primary quantities of cells. For in vivo studies,
      an orthotopic rat bladder carcinoma was used. The animals were treated
      intravenously or intravesically and the tumors were harvested and weighted after
      the study. In contrast to other authors we could not find any anti-proliferative
      effect, we actually showed that instillation into the rat urinary bladder
      enhanced tumor growth.

PMID- 19578785
TI  - Stereotactic radiotherapy in recurrent gynecological cancer: a case series.
AB  - Scarce data are available on the use of extracranial stereotactic radiotherapy in
      recurrent gynecological tumors. The aim of this report was to analyze the results
      of our preliminary experience with extracranial stereotactic radiotherapy in
      locally or distantly recurrent gynecological tumors. Extracranial stereotactic
      radiotherapy was planned by the Precise-Plan treatment planning system. Patients
      were immobilized using the Stereotactic Body-Frame. Five consecutive daily
      fractions were delivered; dose/fraction and total dose were defined based on an
      institutional dose-escalation protocol. A class solution with 4 non-coplanar
      fixed beams based on the tetrad configuration was used in all patients. Eleven
      patients (12 lesions), were included in the analysis. Stereotactic radiotherapy
      was delivered as first radiotherapy treatment (5 patients), or as retreatment (6
      patients). Complete clinical response was achieved in 8/12 lesions (66.6%), while
      partial response was documented in 2/12 lesions (16.6%). With a median follow-up
      of 19 months (range, 2-37 months), 7 patients (63%) experienced local and/or
      distant progression of disease. The 2-year local progression-free survival was
      81.8%, while the 2-year metastases-free survival was 54.4%. The 2-year overall
      survival was 63.6%. Acute and late toxicities were grade 2 or less. There was no
      difference in quality of life scores between the data collected before
      extracranial stereotactic radiotherapy and at first follow-up evaluation.
      Fractionated extracranial stereotactic radiotherapy administered up to a dose of
      30 Gy in five fractions is well tolerated. Further studies of extracranial
      stereotactic radiotherapy and novel radiotherapy techniques are warranted in the
      challenging setting of recurrent gynecological tumors.

PMID- 19578786
TI  - Prognostic index reflecting genetic alteration related to disease-free time for
      gastric cancer patient.
AB  - The study purpose was to develop a patient's prognostic index (PI) reflecting the
      genetic information in cDNA microarray-based CGH experiment data for estimating a
      gastric cancer patient's survival time. The developed methodology was fit to and
      validated using data from the Cancer Metastasis Research Center at Yonsei
      University; 30 pairs of gastric tumors and normal gastric tissues were used in
      the cDNA microarray-based CGH. The cDNA microarrays containing 17,000 sequence
      verified human gene probes were directly compared. Genetic alteration score (GAS)
      was constructed based on the genes that had a high frequency of alteration among
      all the genes displaying small variations across the arrays. GAS was determined
      using a technique that finds linear combinations of the original variables that
      best account for the variability in the data. When classifying cancer patients
      with the PI predicted by the model incorporating GAS, the correct classification
      rate for recurrence was 83.33%. In conclusion, GAS allowed for providing an
      independent patient's PI that reflects the genetic information for prognosis on
      hazard rate of recurrence, which was capable of distinguishing a patient's
      recurrence status, survival status and cancer stage status. The predicted PI also
      provided each patient's estimated disease-free survival rate. In this study, 82
      genes were selected for analysis based on a high frequency of alteration and
      small variations across the arrays. In addition, 13 genes displaying a possible
      relationship with disease-free survival time were identified. GAS was found to be
      associated with the recurrence status and survival status.

PMID- 19578787
TI  - Matrix metalloproteinases and their inhibitors as markers of inflammation and
      fibrosis in chronic liver disease (Review).
AB  - Chronic liver disease (CLD) is a cause of morbidity and mortality worldwide, due
      to haemodynamic and metabolic complications of liver cirrhosis. During CLD the
      extracellular matrix undergoes a process of remodelling, leading to new collagen
      formation and deposition. Tissue remodelling is regulated by fine molecular
      mechanisms, involving proteases, inhibitors and growth factors. The major role in
      matrix degradation is played by matrix metalloproteinases (MMPs), a class of zinc
      and calcium-dependent enzymes, and their tissue inhibitors (TIMPs). Along with
      the progress in diagnostic techniques, leading to more precise and less invasive
      methods, the concept of monitoring has gained importance for the clinical
      management of CLD. At the present state of our knowledge, liver biopsy still
      represents an essential procedure for staging liver disease. However, despite its
      importance, liver biopsy presents some limitations: the risk of a disease
      underestimation is the most significant one, as hepatic lesions are often
      irregularly located within the liver. Parallel to the limitations of liver
      biopsy, clinical needs for an early identification of progressive fibrosis
      require additional non-invasive techniques to be developed. In this review we
      discuss the major problems concerning this important clinical necessity.
      Moreover, we focus on the role of MMPs and TIMPs in the pathogenesis of CLD, as
      well as their possible use as non-invasive serum markers for inflammation and
      fibrosis in this pathology.

PMID- 19578788
TI  - UVB radiation induces human lens epithelial cell migration via NADPH oxidase
      mediated generation of reactive oxygen species and up-regulation of matrix
      metalloproteinases.
AB  - Ultraviolet (UV) radiation is one of the important cataract risk factors. The
      migration of human lens epithelial cells (HLECs) plays a crucial role in the
      remodeling of lens capsule and cataract formation. The purpose of the present
      study was to investigate the molecular mechanisms of UV-induced lens cell
      migration. We found that UVB radiation induces cell migration in cultured human
      lens epithelial cells. Further, we observed that UVB radiation induces NADPH
      oxidase activity and ROS generation which are inhibited by NADPH oxidase
      inhibitor diphenylene iodonium or DPI and antioxidant epigallocatechin gallate
      (EGCG). In addition, DPI and EGCG also block UVB irradiation-induced MMP-2, and 
      9 activity and expression and nuclear translocation of NF-kappaB. Collectively,
      our data suggest that NADPH oxidase may be a major source for the UVB-induced ROS
      generation, and it plays an essential role in the activation of NF-kappaB, which
      is involved in the activities of MMP-2 and MMP-9 and cell migration induced by
      UVB in HELCs. Understanding the cell signaling pathways may constitute potential
      therapeutic targets in for UVB-induced cataract.

PMID- 19578789
TI  - Reciprocal regulation of IL-6 and IL-10 balance by HGF via recruitment of heme
      oxygenase-1 in macrophages for attenuation of liver injury in a mouse model of
      endotoxemia.
AB  - Acute liver injury is a clinical hallmark of endotoxemia regarding the features
      of septic organ failure. In this process, interleukin (IL)-6 and IL-10 are key
      contributors for eliciting pro- and anti-inflammatory responses, respectively. In
      contrast, heme oxygenase-1 (HO-1) provides a defense mechanism against
      endotoxemia by controlling the IL-6/IL-10 balance, but how higher levels of HO-1
      are sustained under pathological conditions remains unknown. Using a mouse model
      of endotoxemia, we provide evidence to show that hepatocyte growth factor (HGF)
      enhances HO-1 expression in macrophages, thereby up-regulating IL-10 and down
      regulating IL-6 productions. Lipopolysaccharide (LPS)-treated mice manifested
      acute liver injury similar to that observed in septic patients, while
      administration of recombinant HGF enhanced expression of HO-1 by hepatic
      macrophages in vivo. As a result, HGF blocked the onset of hepatic injuries in
      LPS-treated mice. More importantly, when an HO-1 inhibitor (Sn-PP) was
      administered with HGF into LPS-treated mice, the protective effects of HGF
      against hepatic injury were attenuated. Furthermore, Sn-PP partially restored the
      HGF-mediated decrease in plasma IL-6 levels, while it inhibited the HGF
      stimulated increase in plasma IL-10 levels. In the culture of macrophages
      (Raw264.7), HGF enhanced the LPS-mediated HO-1 induction, and this effect was
      abolished by cycloheximide, but not by actinomycin-D, thus suggesting that a post
      transcriptional pathway is involved in HGF-mediated up-regulation of HO-1. Based
      on the current data, we conclude that up-regulation of HO-1 plays an important
      role in HGF-mediated hepatoprotection during endotoxemia, by favoring production
      of IL-10 over IL-6.

PMID- 19578790
TI  - Pro-oxidant-mediated hepatic fibrosis and effects of antioxidant intervention in
      murine dietary steatohepatitis.
AB  - The mechanistic significance of oxidative stress to fibrogenesis in the
      methionine and choline-deficient (MCD) diet-induced model of steatohepatitis was
      evaluated by antioxidant intervention, using either vitamin E or L-2
      oxothiazolidine-4-carboxylate (OTC), a cysteine precursor that promotes
      glutathione synthesis. Significant depletion of hepatic reduced glutathione (GSH)
      and elevation of thiobarbituric acid reactive substances (TBARS) occurred from
      week 3 in association with hepatic injury in mice fed the MCD diet. Hepatic
      stellate cell (HSC) activation and increased collagen alpha1(I) mRNA expression,
      together with morphologic fibrosis were evident from week 5. Vitamin E repleted
      GSH, reduced TBARS, steatosis, inflammation, HSC activation and collagen
      alpha1(I) mRNA expression, and ameliorated fibrosis. Vitamin E did not effect the
      expression of either profibrogenic cytokines (transforming growth factor-beta 1,
      connective tissue growth factor) or matrix remodeling enzymes (tissue inhibitor
      of metalloproteinase-1 and -2, matrix metalloproteinase-2 and -13). Despite
      repletion of hepatic GSH in OTC-supplemented mice, the initial benefit in the
      reduction of hepatic TBARS and inhibition of collagen alpha1(I) mRNA expression
      at week 5, failed to protect these mice from hepatic injury or fibrosis at later
      time points. Oxidative stress or products of lipid peroxidation mediate HSC
      activation and collagen gene expression directly in the MCD model of
      steatohepatitis. Vitamin E but not glutathione augmentation can interrupt this
      pathogenic process.

PMID- 19578791
TI  - CR1 genotype and haplotype involvement in coronary artery disease: the pivotal
      role of hypertension and dyslipidemia.
AB  - Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and
      coronary syndromes. Atherosclerosis is a complex multifactorial disorder. Data
      indicate that the complement proteins play a crucial role in the link between
      inflammation and atherogenesis. Thus, there is evidence supporting the role of
      complement activation in atherogenesis. Complement receptor 1 (CR1) is a membrane
      protein found on different cells involved in various activities of the complement
      system. We demonstrated the possible involvement of CR1 in atherosclerosis
      studying the allele and genotype frequencies of the CR1 Pro1827Arg, CR1
      His1208Arg exon 22 and int27 HindIII polymorphisms in a sample of patients with
      angiographically documented coronary artery disease (CAD) (n=550) and in healthy
      controls (n=380) matched for age, gender and ethnicity. Our data showed no
      significant deviations between the two groups with regard to either allele or
      genotype frequencies. After stratification according to risk factors, our
      analysis revealed a reduced frequency of the GG genotype of the Pro1827Arg
      polymorphism in patients with CAD and dyslipidemia vs the controls (p=0.031) and
      of the GG and LL genotypes in CAD patients with dyslipidemia vs CAD patients
      without dyslipidemia regarding the Pro1827Arg and CR1 HindIII intron 27
      polymorphisms (GG, p=0.019; LL, p=0.184). We analyzed the haplotype frequencies
      of CR1. A decrease in CAD patients carrying the CAC haplotype compared to
      controls (p=0.043) and a decrease in the CAC haplotype in CAD patients with
      hypertension vs healthy controls (p=0.029) were demonstrated. Our data showed a
      possible involvement of CR1 gene polymorphisms in the predisposition to the
      development of this disease.

PMID- 19578792
TI  - Realgar-mediated growth inhibition on HaCaT human keratinocytes is associated
      with induction of apoptosis.
AB  - Traditional Chinese medicine has long been used to treat a variety of ailments
      including skin diseases. Our previous study has revealed the ethanolic extract of
      realgar, a common ingredient used in psoriasis treatment in Chinese medicine, to
      possess potent anti-proliferative action on cultured HaCaT cells of human
      keratinocyte origin. In the present study, the mechanisms of action of the
      observed growth inhibitory action of realgar were investigated. Several bioassay
      methods were employed to elucidate whether cellular apoptosis is involved in the
      realgar-induced growth inhibition of the skin cells. Morphologically, nuclear
      condensation and DNA fragmentation were observed when HaCaT cells were exposed to
      the realgar extract. DNA fragmentation induced by the treatment of realgar was
      also evident as detected by gel electrophoresis and the TUNEL method. Cell cycle
      analysis by propidium iodide (PI) staining demonstrated the appearance of sub-G1
      peak and cell cycle arrest at the G1 phase upon realgar treatment. Quantitative
      analysis by annexin V-PI staining revealed that the realgar-induced apoptotic
      event was dose-dependent. Furthermore, realgar was able to activate caspase-3
      expression when examined by Western blot analysis. Our experimental data
      unambiguously confirm that induction of cellular apoptosis is mainly responsible
      for the observed growth inhibition brought about by realgar on the HaCaT
      keratinocytes, and this finding helps place the traditional use of this mineral
      for psoriasis treatment on a scientific footing.

PMID- 19578793
TI  - (-)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by
      sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt
      pathway in osteoblasts.
AB  - We previously reported that sphingosine 1-phosphate stimulates the induction of
      heat shock protein 27 (HSP27) through p38 mitogen-activated protein (MAP) kinase
      and phosphatidylinositol 3-kinase/Akt in osteoblast-like MC3T3-E1 cells. In the
      present study, we investigated whether (-)-epigallocatechin gallate (EGCG), the
      major polyphenol found in green tea, affects the induction of HSP27 in these
      cells and its mechanism, since it was previously reported that catechin,
      including EGCG, suppresses bone resorption. EGCG significantly reduced the
      induction of HSP27 stimulated by sphingosine 1-phosphate in a dose-dependent
      manner between 10 and 30 microM. Immunofluorescence microscopy studies revealed
      that sphingosine 1-phosphate certainly stimulated the induction of HSP27 in the
      cytosol of these cells, and that EGCG clearly suppressed its induction. However,
      sphingosine 1-phosphate-stimulated phosphorylation of p38 MAP kinase or MAPKAP-2
      was not affected by EGCG. By contrast, EGCG markedly suppressed the
      phosphorylations of both Akt and glycogen synthase kinase-3beta stimulated by
      sphingosine 1-phosphate. These results strongly suggest that EGCG suppresses the
      induction of HSP27 stimulated by sphingosine 1-phosphate via attenuation of, not
      the p38 MAP kinase pathway, but of the phosphatidylinositol 3-kinase/Akt pathway
      in osteoblasts.

PMID- 19578794
TI  - Systemic cell-cycle suppression by Apicidin, a histone deacetylase inhibitor, in
      MDA-MB-435 cells.
AB  - Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of
      potential anti-cancer agents for the treatment of solid and hematological
      malignancies. However, the best characterized HDAC function concerns the control
      of gene expression via the regulation of transcription activation or repression.
      To understand the genome-wide effects of HDAC inhibition on gene regulation, we
      performed serial gene expression analyses from 0 to 48 h after treating MDA-MB
      435, a melanoma-derived highly metastatic tumor cell line, with Apicidin, a HDAC
      inhibitor. Combined-transcriptomic analysis of large-scale molecular changes
      induced by Apicidin resulted in the identification of 631 outlier genes that were
      continuously up- or down-regulated during the 48 h study period. When the 631
      outlier genes were mapped to known biological processes, cell-cycle suppression
      emerged as the function most elicited by Apicidin. In addition comprehensive
      negative cell-cycle regulation by Apicidin was dissected using gene expression
      data and validated by Western blot analysis. We suggest the 631 outlier genes as
      a characteristic molecular signature for Apicidin, and propose concurrent
      transcriptional suppression of major components of cell-cycle regulatory circuit
      as potent anti-tumor mechanism of Apicidin. Genetic elements identified during
      this study also provide the possibility of novel therapeutic interventions in
      tumor metastasis.

PMID- 19578795
TI  - Activity of the 5-HT1A receptor is involved in the alteration of glucocorticoid
      receptor in hippocampus and corticotropin-releasing factor in hypothalamus in SPS
      rats.
AB  - Rats exposed to single-prolonged stress (SPS) showed enhanced inhibition of the
      hypothalamic-pituitary-adrenal (HPA) system and alteration in the
      glucocorticoid/mineralocorticoid receptor. Dysfunction of the HPA axis is one of
      the core neuroendocrine abnormalities of post-traumatic stress disorder (PTSD).
      Serotonergic receptor, glucocorticoid receptor (GR) and corticotropin-releasing
      factor (CRF) have been proposed to play major roles in dysfunction of the HPA
      axis. However, the precise molecular mechanism is unknown. In this study, we
      investigated the relationships between the changes of GR in hippocampus as well
      as CRF in hypothalamus and the activity of 5-HT1A receptor in SPS rats. We
      exposed rats to SPS with or without prior treatment with WAY100635 (the 5-HT1A
      receptor antagonist), and observed behavioral changes, GR levels in the
      hippocampus and CRF levels in the hypothalamus by immunohistochemistry, Western
      blotting and RT-PCR seven days after SPS. Our results demonstrate that SPS
      increases expression of GR and CRF, which were partially inhibited by WAY-100635.

PMID- 19578796
TI  - Association of genetic variants with chronic kidney disease in individuals with
      different lipid profiles.
AB  - The purpose of the present study was to identify genetic variants that confer
      susceptibility to chronic kidney disease (CKD) in individuals with low or high
      serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)
      cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing
      to the personalized prevention of CKD in such individuals. The study population
      comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated
      glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 4238 controls
      (eGFR>or=60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate
      genes were determined. The Chi-square test, multivariable logistic regression
      analysis with adjustment for covariates, and a stepwise forward selection
      procedure revealed that seven different polymorphisms were significantly
      (P<0.005) associated with the prevalence of CKD in individuals with low or high
      serum concentrations of TG or HDL- or LDL-cholesterol: the Aright curved arrow G
      (Glu23Lys) polymorphism of KCNJ11 and the 125592Cright curved arrow A (Thr431Asn)
      polymorphism of ROCK2 in individuals with low serum TG; the 734Cright curved
      arrow T (Thr254Ile) polymorphism of ACAT2 and the Cright curved arrow G
      (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the 
      1607/1Gright curved arrow 2G polymorphism of MMP1 in individuals with low serum
      HDL-cholesterol; the Gright curved arrow A (Val158Met) polymorphism of COMT in
      individuals with low serum LDL-cholesterol; the 584Gright curved arrow A
      (Gln192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol.
      No polymorphism was associated with CKD in individuals with high serum HDL
      cholesterol. These results suggest that polymorphisms associated with CKD may
      differ among individuals with different lipid profiles. Stratification of
      subjects according to lipid profiles may thus be important for personalized
      prevention of CKD based on genetic information.

PMID- 19578797
TI  - Integrative genomic analyses of WNT11: transcriptional mechanisms based on
      canonical WNT signals and GATA transcription factors signaling.
AB  - We and others previously cloned and characterized vertebrate WNT11 orthologs,
      which are involved in gastrulation, neurulation, cardiogenesis, nephrogenesis,
      and chondrogenesis during fetal development. WNT11 orthologs activate both
      canonical and non-canonical WNT signaling cascades depending on the expression
      profile of WNT receptors, such as Frizzled family members, LRP6, ROR2, and RYK.
      Human WNT11 is expressed in breast cancer, gastric cancer, esophageal cancer,
      colorectal cancer, neuroblastoma, Ewing sarcoma, and prostate cancer. Canonical
      WNT signals and GATA family members are involved in WNT11 transcription during
      embryogenesis of model animals; however, precise mechanisms of WNT11 expression
      remain unclear. Here, refined integrative genomic analyses of WNT11 are carried
      out to elucidate the mechanisms of WNT11 transcription. The WNT11 gene was found
      to encode two isoforms by using alternative first exons. WNT11 isoform A
      (NM_004626.2 RefSeq) consists of exons 2, 3, 4, 5 and 6, whereas WNT11 isoform B
      consists of exons 1, 2, 3, 4, 5 and 6. We identified double TCF/LEF-binding sites
      within the proximal promoter regions -48-bp position from the TSS of human WNT11
      isoform B and -43-bp position from the TSS of human WNT11 isoform A), and also
      double GATA-binding sites within intron 2 of human WNT11 gene (+933-bp and +5001
      bp positions from TSS of human WNT11 isoform A). Double TCF/LEF- and double GATA
      binding sites within the regulatory regions of human WNT11 gene were conserved in
      other mammalian WNT11 orthologs. These facts indicate that canonical WNT signals
      and GATA family members directly upregulate WNT11 transcription. Canonical WNT
      induced WNT11 activates non-canonical WNT signaling cascades to induce cellular
      movement, and also activates the Ca2+-MAP3K7-NLK signaling cascade to break the
      canonical WNT signaling. Canonical WNT-to-WNT11 signaling loop is involved in
      cellular migration during embryogenesis as well as tumor invasion during
      carcinogenesis.

PMID- 19578798
TI  - Growth inhibition of estrogen receptor positive human breast cancer cells by
      Taheebo from the inner bark of Tabebuia avellandae tree.
AB  - Selective estrogen receptor (ER) modulators are used as a therapy for ER+
      clinical breast cancer, but they exhibit adverse effects. Herbal medicines may
      provide an alternative or complementary approach. Taheebo, extracted from the
      inner bark of the Tabebuia avellandae tree found in the Brazilian Amazon,
      exhibits selective anti-proliferative effects in carcinoma cell lines. The
      present study identifies the mechanistic leads for the inhibitory effects of
      Taheebo. Human breast carcinoma derived ER+MCF-7 cells were used as the model.
      Aqueous extract of Taheebo was the test compound. Cell cycle analysis, clonogenic
      assay, and global gene expression profiles were the quantitative parameters.
      Taheebo treatment resulted in a dose/time-dependent growth inhibition (S phase
      arrest, reduced clonogeneticity) and initiation of apoptosis (chromatin
      condensation). A 6-h treatment with 1.5 mg/ml Taheebo modulated the gene
      expression of G2 specific cyclin B1 (-2.0-fold); S phase specific PCNA (-2.0
      fold) and OKL38 (+11.0-fold); apoptosis specific GADD-45 family (+1.9-5.4-fold),
      Caspases (+1.6-1.7-fold), BCL-2 family (-1.5-2.5-fold), estrogen responsive ESR1
      (-1.5-fold), and xeno-biotic metabolism specific CYP 1A1 (+19.8 fold) and CYP 1B1
      (+7.9-fold). The anti-proliferative effects of Taheebo correlate with down
      regulated cell cycle regulatory and estrogen responsive genes, and up-regulated
      apoptosis specific and xeno-biotic metabolism specific genes. These data validate
      a rapid mechanistic approach to prioritize efficacious herbal medicines, thereby
      complementing the existing endocrine therapy for breast cancer.

PMID- 19578799
TI  - The effects of buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4
      triazole on propyl gallate-treated HeLa cells in relation to cell growth,
      reactive oxygen species and glutathione.
AB  - Propyl gallate (PG) as a synthetic antioxidant is widely used in processed food
      and medicinal preparations. It also exerts a variety of effects on tissue and
      cell functions. In the present study, we investigated the effects of L-buthionine
      sulfoximine (BSO, an inhibitor of GSH synthesis), diethyldithiocarbamate (DDC, an
      inhibitor of Cu/Zn-SOD) or 3-amino-1,2,4-triazole (AT, an inhibitor of catalase)
      on PG-treated HeLa cells in relation to cell growth, reactive oxygen species
      (ROS) and glutathione (GSH). Treatment with PG induced growth inhibition, the
      loss of mitochondrial membrane potential [MMP (DeltaPsim)] and apoptosis in HeLa
      cells. ROS levels including O2.- were increased or decreased in PG-treated HeLa
      cells depending on the incubation times. PG caused depletion in GSH content in
      HeLa cells. While BSO enhanced the growth inhibition of PG-treated HeLa cells at
      4 h, DDC and AT did not. All the agents down-regulated MMP (DeltaPsim) levels in
      PG-treated cells. Although BSO, DDC or AT slightly increased ROS or O2.- levels
      in PG-treated cells at 1 h, these enhancements of ROS did not intensify apoptosis
      in these cells. In addition, BSO, DDC or AT slightly reduced GSH level in PG
      treated HeLa cells at 1 h, but this reduction did not affect cell death of HeLa.
      Furthermore, PG induced a G1 phase arrest of the cell cycle. BSO, DDC or AT
      significantly inhibited the G1 phase arrest in PG-treated cells. Conclusively,
      the changes of ROS and GSH levels by BSO, DDC or AT in PG-treated HeLa cells did
      not strongly affect the cell growth and death.

PMID- 19578800
TI  - The metabolic syndrome of omega3-depleted rats. III. Brain phospholipids.
AB  - Rats exposed from 7 weeks after birth and for the ensuing 3 to 7 months to a diet
      depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed
      as a new animal model for the metabolic syndrome. The present study aimed mainly
      at investigating whether, in this new model, the perturbation of the fatty acid
      total content and pattern of brain phospholipids simulates that previously
      documented in second-generation omega3-depleted rats. Such was indeed the case,
      with the apparent exception of changes in the C18:1omega9, C20:0, C22:0 and C24:0
      relative content of brain phospholipids. Moreover, the C22:5omega3 content of
      such phospholipids was unexpectedly lower in the present model than in the second
      generation omega3-depleted rats. The changes in brain phospholipids were also
      monitored when the rats deprived of omega3 fatty acids for 7 months were given
      access for 2 to 4-5 weeks to a flaxseed oil-enriched diet. Most phospholipid
      variables were rapidly normalized under the latter experimental conditions. The
      results obtained under these conditions suggest that an increase in the brain
      phospholipid C22:5omega3 content may play a key role in the orexigenic effects of
      exogenous omega3 fatty acids supplied to omega3-depleted animals.

PMID- 19578801
TI  - First episode psychosis and the trail to secondary care: help-seeking and health
      system delays.
AB  - BACKGROUND: People experience delays in receiving effective treatment for many
      illnesses including psychosis. These delays have adverse consequences in heart
      disease and cancer, and their causes have been the subject of much research but
      only in recent years have pathways to care in psychosis received such attention.
      We sought to establish if, when and where people seek help in the early phase of
      psychosis in a representative sample. METHODS: One hundred and sixty-five people
      with first episode psychosis, referred from community-based psychiatric services
      and a private psychiatric facility to an early intervention service over 18
      months, were interviewed with the Structured Clinical Interview for DSM-IV
      diagnoses. Symptoms were measured using the Schedule for the Assessment of
      Positive Symptoms, Schedule for the Assessment of Negative Symptoms and the
      Calgary Scale. Duration of untreated illness (DUI) and duration of untreated
      psychosis (DUP) were established using the Beiser Scale. Pathways to mental
      health services were systematically detailed through interviews with patients and
      their families. RESULTS: The final sample consisted of 142 (88M, 54F) cases after
      those with psychosis due to a general medical condition and those without pathway
      and DUP data were excluded. Less than half of participants initiated help seeking
      themselves. Of those who did seek help (n = 57) 25% did so during the DUI. Those
      who had a positive family history of mental illness and poorer premorbid
      adjustment were significantly less likely to seek help for themselves and those
      who did not seek help were more likely to require hospitalisation. Families were
      involved in help seeking for 50% of cases and in 1/3 of cases did so without the
      affected individual participating in the contact. Being younger and having more
      negative symptoms were associated with having one's family involved in help
      seeking. Delays to effective treatment from the onset of psychosis were evenly
      split between "help-seeking delays" and "health-system delays". Having a family
      member involved in help seeking and better premorbid adjustment were
      independently associated with shorter help-seeking delays when measured from the
      onset of psychosis. Being female, having better premorbid adjustment and fewer
      negative symptoms were associated with shorter help-seeking delays from the onset
      of illness. Those with a non-affective psychosis had significantly longer system
      delays. CONCLUSION: Many people with first episode psychosis do not initiate help
      seeking for themselves particularly those with a relative affected by mental
      illness. Those with poor premorbid adjustment are at particular risk of longer
      delays. Poor premorbid adjustment compounded by long delays to effective
      treatment reduces the likelihood of a good outcome. Families play a vital role in
      hastening receipt of effective treatment.

PMID- 19578802
TI  - Oral hormonal contraceptives affect the concentration and composition of urinary
      glycosaminoglycans in young women.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary glycosaminoglycans (uGAG) have protective
      effects against urinary tract disorders. Here we investigated whether oral
      hormonal contraceptives (OC) affect uGAG excretion. METHODS: Urine specimens were
      from young women regularly taking: ethinyl estradiol + drospirenone, n = 9;
      ethinyl estradiol + cyproterone acetate, n = 9; and ethinyl estradiol +
      gestodene, n = 7. Controls were from ten women not taking OC. Total uGAG was
      assayed as hexuronic acid/urinary creatinine. Sulfated uGAG species was
      determined by electrophoresis. RESULTS: Unlike controls, total uGAG in the two
      halves of the menstrual cycle was similar in the OC groups. Whole cycle uGAG was
      higher in the OC groups (p < 0.01), especially for ethinyl estradiol +
      cyproterone acetate (p < 0.005). The three OC produced decreases of approximately
      50% in heparan sulfate (p < 0.02) and dermatan sulfate (p < 0.02), and a
      approximately 100% increase in chondroitin sulfate (p < 0.004). CONCLUSIONS: uGAG
      excretion is changed in women taking OC, and this might enhance the protective
      effects of these molecules against urinary tract disorders.

PMID- 19578803
TI  - Validation of the Prolapse Quality-of-Life Questionnaire (P-QoL) in Portuguese
      version in Brazilian women.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study is to validate the Portuguese
      translated version of the Prolapse Quality-of-Life Questionnaire (P-QoL).
      METHODS: Ninety-eight women completed the P-QoL questionnaire translated into
      Portuguese at baseline and on the second visit, 2 weeks later. Clinical data and
      Pelvic Organ Prolapse Quantification Index (POP-Q) according to the International
      Continence Society were obtained. Psychometric properties of the questionnaire
      were assessed. RESULTS: Sixty-eight symptomatic and 30 asymptomatic women for POP
      symptoms were studied. Most patients presented POP-Q > 2. The P-QoL demonstrated
      good psychometric properties. The test-retest reliability confirmed a highly
      significant stability between the total scores for each domain (P < 0.0001). The
      construct validation distinguished differences in P-QoL questionnaire scores
      between symptomatic and asymptomatic women. CONCLUSION: The Portuguese version of
      the P-QoL questionnaire is a valid and reliable instrument to assess quality of
      life in Brazilian women with pelvic organ prolapse.

PMID- 19578805
TI  - Morphometry of sacral hiatus and its clinical relevance in caudal epidural block.
AB  - BACKGROUND: Sacral approach to epidural space produces reliable and effective
      block of sacral nerves. It is necessary to have a detailed knowledge of sacral
      hiatus (SH) for optimal access into sacral epidural space. This study was
      undertaken to evaluate various landmarks of SH. METHODS: One hundred and fourteen
      adult dry human sacral bones were examined for morphometric analysis using
      vernier caliper. SH was categorized on the basis of shape. RESULTS: Most commonly
      encountered shape of hiatus was inverted U (40.35%). Its apex and base were most
      commonly observed against fourth and fifth sacral vertebrae, respectively.
      Various defects in dorsal wall of sacral canal were recorded. Height and
      anteroposterior depth at the apex of hiatus were ranged 4.30-38.60 and 1.90-10.40
      mm, respectively. Mean intercornual distance at base was 11.95 +/- 2.78 mm. The
      triangle formed by right and left posterior superior iliac spines and apex of SH
      was found equilateral in 45% cases only. Sacral cornua were marked by their
      bilateral presence in 55.26% and impalpable in 21.05% cases. Minimum distance
      between S2 and apex was 7.25 mm which suggested that it would not be safe to push
      the needle beyond 7 mm into sacral canal so as to avoid dural puncture. In 8.77%
      cases, depth of hiatus was less than 3 mm. CONCLUSIONS: Single bony landmark may
      not help in locating SH because of anatomical variations. Depth of hiatus less
      than 3 mm may be one of the causes for failure of needle insertion. Surrounding
      bony irregularities, different shapes of hiatus and defects in dorsal wall of
      sacral canal should be taken into consideration before undertaking caudal
      epidural block so as to avoid its failure.

PMID- 19578804
TI  - Relationship between the mandibular inferior cortex and bone stiffness in elderly
      Japanese people.
AB  - SUMARRY: This study assessed the relationship between the mandibular inferior
      cortex (MIC) and bone stiffness in elderly Japanese subjects. Results suggest
      that MIC classification may be useful for screening patients for the possibility
      of osteoporosis by measuring bone stiffness with ultrasound bone densitometry.
      INTRODUCTION: The prevention of fractures is a priority for patients with
      osteoporosis. Dental panoramic radiographs are frequently taken for the
      examination of teeth and jaws in general dental practice worldwide. This study
      assessed the relationship between the mandibular inferior cortex (MIC) and bone
      stiffness in elderly Japanese subjects. METHODS: This study included 519 healthy
      subjects (263 men and 256 women) aged 70 years old. We evaluated the relationship
      between MIC classification and bone stiffness using Scheffe's multiple comparison
      test. Multiple linear regression analysis was used to assess the relationship
      between MIC classification and bone stiffness after controlling for confounding
      factors. RESULTS: A significant correlation was found between MIC classification
      and bone stiffness in men (C1 vs C2: p < 0.05) and women (C1 vs C2: p = NS, C1 vs
      C3: p < 0.01, C2 vs C3: p < 0.05). MIC classification was significantly
      associated with bone stiffness on multiple linear regression analysis after
      controlling for sex, body mass index, regular exercise, and smoking (beta = 
      0.11, p < 0.01, R(2) = 0.387, p < 0.001). CONCLUSIONS: Our study suggests that
      MIC classification may be useful for screening patients for the possibility of
      osteoporosis by measuring bone stiffness with ultrasound bone densitometry.

PMID- 19578806
TI  - Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered
      mental status.
AB  - The authors present a case of a 56-year-old man with altered mental status.
      Magnetic resonance imaging (MRI) of the brain revealed non-enhancing
      abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum.
      Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After
      treatment with methotrexate, he improved clinically without focal sensorimotor
      deficits and with improving orientation. MRI showed almost complete resolution of
      brainstem and cerebral lesions. To the authors' knowledge, there are only five
      previous reports of primary central nervous system T-cell lymphoblastic lymphoma.
      Since treatable, it deserves consideration in patients with altered mental status
      and imaging abnormalities that include diffuse, non-enhancing changes with
      increased signal on T2-weighted images.

PMID- 19578807
TI  - High weight or body mass index increase the risk of vertebral fractures in
      postmenopausal osteoporotic women.
AB  - In the general population, low body weight and body mass index (BMI) are
      significant risk factors for any fracture, but the specific association between
      body weight, BMI, and prevalence of vertebral fractures in osteoporotic women is
      not fully recognized. Hence, the association between body weight, BMI, and
      prevalent vertebral fractures was investigated in 362 women with never-treated
      postmenopausal osteoporosis. All participants underwent measurement of BMI, bone
      mineral density (BMD), and semiquantitative assessment of vertebral fractures.
      Thirty percent of participants had > or =1 vertebral fracture. Body weight and
      BMI were associated with L1-L4 BMD (R = 0.29, P < 0.001 and R = 0.17, P = 0.009,
      respectively). In logistic regression analysis, BMI was positively associated
      with the presence of vertebral fractures independent of age and other traditional
      risk factors for fractures. Including weight and height instead of BMI in the
      multivariate model, showed weight as a positive and significant covariate of the
      presence of vertebral fractures (OR = 1.045; P = 0.016; 95% CI 1.008-1.084). BMI
      was associated with the number of vertebral fractures (rho = 0.18; P = 0.001),
      this association being confirmed also in the multivariate analysis (beta = 0.14;
      P = 0.03) after correction for smoking, early menopause, family history of
      fragility fractures and BMD. In conclusion, among postmenopausal women with
      osteoporosis, body weight and BMI are associated with a higher likelihood of
      having a vertebral fracture, irrespective of the positive association between
      weight and BMD.

PMID- 19578808
TI  - Normochromic normocytic anemia in a postmenopausal woman with severe osteoporosis
      treated with intermittent parathyroid hormone.
AB  - Intermittent exogenous parathyroid hormone (PTH) is a potent osteoanabolic agent
      used for the treatment of severe osteoporosis. Two molecules of recombinant PTH
      are commercially available: the full-length PTH (PTH 1-84) and teriparatide (PTH
      1-34). We present the first report of PTH-induced mild, asymptomatic,
      normochromic normocytic anemia in a postmenopausal woman treated sequentially
      with PTH 1-84 and PTH 1-34. Anemia was more pronounced with PTH 1-84 compared to
      PTH 1-34 and was reversed with each regimen discontinuation. We suggest
      monitoring of hematocrit and hemoglobin in PTH-treated patients, especially when
      PTH 1-84 is used.

PMID- 19578810
TI  - Inflammatory cytokines, endothelial markers and adhesion molecules in rheumatoid
      arthritis: effect of intensive anti-inflammatory treatment.
AB  - Tumour necrosis factor alpha (TNF-alpha) and interlekin-6 (IL-6) are key
      inflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA), a
      disease also associated with endothelial perturbation and increased serum levels
      of adhesion molecules. As relationships between these processes and molecules are
      unclear, we tested the hypotheses (a) that TNF-alpha and IL-6 are linked to
      endothelial activation/damage and levels of soluble adhesion molecules, and (b)
      that intensive anti-inflammatory treatment improves levels of these indices. We
      recruited 66 patients with RA, 48 community controls (CC), and 25 disease
      controls (DC). Plasma TNF-alpha and IL-6 were compared to markers of vascular
      biology (vWF, sE-sel), soluble adhesion molecules (sICAM, sVCAM) and routine
      inflammatory markers (CRP and ESR). Blood was obtained at baseline and at 1 week
      and again 4 weeks after anti-inflammatory treatment in a subgroup of 29 patients
      with RA. With the exception of sE-selectin, RA patients had increased levels of
      all plasma markers compared to the HCs, whilst levels in the DCs were largely
      intermediate between RA and the CCs. Within the RA group, sEsel correlated with
      both CRP and ESR whilst TNF-alpha correlated with sVCAM (all r > 0.32, P < 0.01).
      After 1 week of combined anti-inflammatory therapy, only CRP, ESR, sEsel and
      sVCAM were significantly reduced (all P < 0.05). In RA, endothelial activation
      (as sEsel) correlates with classical markers of inflammation and is reduced by
      intensive anti-inflammatory medications.

PMID- 19578811
TI  - Immunomodulation by statins: mechanisms and potential impact on autoimmune
      diseases.
AB  - Statins are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) and they are the most effective agents for lowering cholesterol in clinical
      practice for the treatment of cardiovascular diseases. However, it has become
      clear that statins also have pleiotropic immunomodulatory effects in addition to
      their lipid-lowering properties. As a result, much attention has been focused on
      their potential as therapeutic agents for the treatment of inflammatory
      autoimmune diseases. In this review the effect of statins on the expression and
      function of a variety of immune-relevant molecules will be discussed alongside
      the underlying mechanisms that contribute to the immunomodulatory effects of
      statins.

PMID- 19578812
TI  - Innate immunity: a key player in the mobilization of hematopoietic
      stem/progenitor cells.
AB  - The mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow
      into peripheral blood (PB) is still not fully understood. Different chemokines,
      cytokines, growth factors, and neurotransmitters have been described that
      facilitate this process. However, mounting evidence suggests that mobilization of
      HSPCs is a part of the immune response and is mediated by innate immunity. We
      discuss evidence showing that complement system cleavage fragments play a crucial
      role in both the retention and mobilization of HSPCs by modulating their
      responsiveness to stromal-derived growth factor-1 (SDF-1) gradient (by C3-derived
      anaphylatoxins) and by modulating the release of granulocytes into PB that
      subsequently facilitate the egress of HSPCs (by C5-derived anaphylatoxins).

PMID- 19578813
TI  - Pathogenicity of the family Legionellaceae.
AB  - The Legionellae are Gram-negative bacteria able to survive and replicate in a
      wide range of protozoan hosts in natural environments, but they also occur in man
      made aquatic systems, which are the major source of infection. After transmission
      to humans via aerosols, Legionella spp. can cause pneumonia (Legionnaires'
      disease) or influenza-like respiratory infections (Pontiac fever). In children,
      Legionnaires' disease is uncommon and is mainly diagnosed in children with
      immunosuppression. The clinical picture of Legionella pneumonia does not allow
      differentiation from pneumonia caused by others pathogens. The key to diagnosis
      is performing appropriate microbiological testing. The clinical presentation and
      the natural course of Legionnaires' disease in children are not clear due to an
      insufficient number of samples, but morbidity and mortality caused by this
      infection are extremely high. The mortality rate for legionellosis depends on the
      promptness of an appropriate antibiotic therapy. Fluoroquinolones are the most
      efficacious drugs against Legionella. A combination of these drugs with
      macrolides seems to be promising in the treatment of immunosuppressed patients
      and individuals with severe legionellosis. Although all Legionella species are
      considered potentially pathogenic for humans, Legionella pneumophila is the
      etiological agent responsible for most reported cases of community-acquired and
      nosocomial legionellosis.

PMID- 19578814
TI  - Serological characterization of the core region of lipopolysaccharides of rough
      Proteus sp. strains.
AB  - INTRODUCTION: Both smooth and rough Proteus sp. strains can be found. The latter
      are characterized by their lack of an O-polysaccharide chain in the
      lipopolysaccharide (LPS) molecule, which makes them suitable for obtaining anti
      core sera. Using this kind of material enables identifying fragments of the
      Proteus LPS core region that might be involved in cross-reactions. To date only a
      few similar epitopes have been established for the genus Proteus. MATERIALS AND
      METHODS: Polyclonal rabbit antisera directed against three rough strains of
      Proteus sp. were tested by enzyme-linked immunosorbent assay (ELISA) with a set
      of LPSs. The reactivity of the selected cross-reactive and homologous systems was
      checked by the Western blot technique and by a passive immunohemolysis assay
      preceded by the absorption of each antiserum with appropriate cross-reactive and
      homologous alkalized LPSs. RESULTS: On the basis of the ELISA results, 19 cross
      reactive antigens were selected among which both smooth and rough LPS forms were
      found. All the observed reactions involved the core region of the LPS. Using the
      antisera absorbed with the appropriate LPSs allowed identification of four groups
      of antigens with serologically identical core regions. CONCLUSIONS: Comparing the
      results of the serological studies with the known chemical structures of the core
      regions of the LPSs used enabled the identification of a few core oligosaccharide
      fragments probably involved in the observed cross-reactions. All were located in
      the most distal part of LPS core region, which made them more easily recognized
      by specific antibodies.

PMID- 19578815
TI  - Immunohistochemical localization of metallothionein and p53 protein in pancreatic
      serous cystadenomas.
AB  - INTRODUCTION: The objective of this study was to determine the expression levels
      of metallothionein (MT) and p53 protein, recognized neoplastic transformation
      markers, in pancreatic serous cystadenomas (SCA) and adenomocarcinomas. MATERIALS
      AND METHODS: Neoplastic pancreatic tissue was taken from 20 patients with
      diagnosed benign (SCA: 5 cases) or malignant tumors (adenomocarcinomas: 15 cases)
      and control pancreatic tissue from healthy persons who had died in car accidents.
      Sections were stained with hematoxylin-eosin. Immunohistochemical localization of
      MT and p53 protein was carried out by LSAB2-HRP using specific antibodies against
      MT and p53. RESULTS: Metallothionein expression was observed only in the
      epithelial cells of the neoplastic tissue of SCAs. MT expression in the
      cystadenomas was weaker than in the healthy pancreatic tissue. No tissue was
      found with p53 protein expression. In the adenomocarcinomas, positive staining
      for MT was observed in 67% and p53 was positive in the carcinoma cells.
      CONCLUSION: The weak MT expression and lack of p53 protein expression in
      pancreatic SCAs confirms the lack of local invasive potential of the neoplastic
      lesion. Increased expressions of MT and p53 were observed in the less
      differentiated tumors. Thus the expression of MT may be a potential prognostic
      marker for tumors.

PMID- 19578816
TI  - Platelet influence on T- and B-cell responses.
AB  - Understanding the adaptive immune response is an area of research critically
      important in medicine. Several positive regulators of B- and T-cell activation
      exist to eliminate pathogens, in which CD40 ligand (CD154) plays a fundamental
      role. It is well documented that CD154 expressed by CD4 T helper cells can be
      critical in the proper activation of dendritic cells for the productive
      stimulation of CD8 T cells and is required for proper T-dependent B-cell
      immunity. However, platelets are an abundant and systemic source of CD154. While
      classically known to be important for hemostasis and inflammation, several lines
      of evidence suggest that platelet-derived ligands can modulate the adaptive
      immune compartment.

PMID- 19578817
TI  - Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal
      cancer patients.
AB  - INTRODUCTION: The aim of the study was to describe the levels of circulating
      monocyte/macrophage pro-inflammatory cytokines (TNF-alpha, IL-1beta IL-6, and IL
      8) and an anti-inflammatory cytokine (IL-10) in inflammatory bowel disease (IBD)
      and colorectal cancer (CRC) patients and healthy controls. MATERIALS AND METHODS:
      The study was conducted on 15 healthy individuals, 20 patients with ulcerative
      colitis (UC), 12 with Crohn's disease (CD), and 15 with CRC (Dukes' stage B).
      Blood serum cytokine levels were measured by ELISA. RESULTS: The patients with UC
      had significantly higher levels of the pro-inflammatory cytokines and of
      circulating IL-10 than the healthy controls. The patients with CD and CRC had the
      same specific pattern of serum cytokines of significantly elevated levels of the
      pro-inflammatory cytokines, but the IL-10 levels were within the range found in
      the healthy individuals. CONCLUSIONS: Thus our results demonstrate that both IBD
      and CRC are linked with an intensified production of a wide array of
      monocyte/macrophage pro-inflammatory cytokines which is not accompanied by
      elevated levels of circulating IL-10, except for its insufficiently inhibitory
      elevation in UC patients.

PMID- 19578818
TI  - Barriers and facilitators to shared decision-making among African-Americans with
      diabetes.
AB  - INTRODUCTION: Shared decision-making (SDM) between patients and their physicians
      is associated with improved diabetes health outcomes. African-Americans have less
      SDM than Whites, which may contribute to diabetes racial disparities. To date,
      there has been little research on SDM among African-Americans. OBJECTIVE: We
      explored the barriers and facilitators to SDM among African-Americans with
      diabetes. METHODS: Qualitative research design with a phenomenological
      methodology using in-depth interviews (n = 24) and five focus groups (n = 27).
      Each interview/focus group was audio-taped and transcribed verbatim, and coding
      was conducted using an iterative process. PARTICIPANTS: We utilized a purposeful
      sample of African-American adult patients with diabetes. All patients had
      insurance and received their care at an academic medical center. RESULTS:
      Patients identified multiple SDM barriers/facilitators, including the
      patient/provider power imbalance that was perceived to be exacerbated by race.
      Patient-related factors included health literacy, fear/denial, family experiences
      and self-efficacy. Reported physician-related barriers/facilitators include
      patient education, validating patient experiences, medical knowledge,
      accessibility and availability, and interpersonal skills. DISCUSSION:
      Barriers/facilitators of SDM exist among African-Americans with diabetes, which
      can be effectively addressed in the outpatient setting. Primary care physicians,
      particularly academic internists, may be uniquely situated to address these
      barriers/facilitators and train future physicians to do so as well.

PMID- 19578819
TI  - Disclosing medical errors to patients: it's not what you say, it's what they
      hear.
AB  - BACKGROUND: There is consensus that patients should be told if they are injured
      by medical care. However, there is little information on how they react to
      different methods of disclosure. OBJECTIVE: To determine if volunteers' reactions
      to videos of physicians disclosing adverse events are related to the physician
      apologizing and accepting responsibility. DESIGN: Survey of viewers randomized to
      watch videos of disclosures of three adverse events (missed mammogram,
      chemotherapy overdose, delay in surgical therapy) with designed variations in
      extent of apology (full, non-specific, none) and acceptance of responsibility
      (full, none). PARTICIPANTS: Adult volunteer sample from the general community in
      Baltimore. MEASUREMENTS: Viewer evaluations of physicians in the videos using
      standardized scales. RESULTS: Of 200 volunteers, 50% were <40 years, 25% were
      female, 80% were African American, and 50% had completed high school. For
      designed variations, scores were non-significantly higher for full
      apology/responsibility, and lower for no apology/no responsibility. Perceived
      apology or responsibility was related to significantly higher ratings (chi
      square, 81% vs. 38% trusted; 56% vs. 27% would refer, p < 0.05), but inclination
      to sue was unchanged (43% vs. 47%). In logistic regression analyses adjusting for
      age, gender, race and education, perceived apology and perceived responsibility
      were independently related to higher ratings for all measures. Inclination to sue
      was reduced non-significantly. CONCLUSIONS: Patients will probably respond more
      favorably to physicians who apologize and accept responsibility for medical
      errors than those who do not apologize or give ambiguous responses. Patient
      perceptions of what is said may be more important than what is actually said.
      Desire to sue may not be affected despite a full apology and acceptance of
      responsibility.

PMID- 19578820
TI  - Are opioid dependence and methadone maintenance treatment (MMT) documented in the
      medical record? A patient safety issue.
AB  - BACKGROUND: Opioid-dependent patients often have co-occurring chronic illnesses
      requiring medications that interact with methadone. Methadone maintenance
      treatment (MMT) is typically provided separately from medical care. Hence,
      coordination of medical care and substance use treatment is important to preserve
      patient safety. OBJECTIVE: To identify potential safety risks among MMT patients
      engaged in medical care by evaluating the frequency that opioid dependence and
      MMT documentation are missing in medical records and characterizing potential
      medication-methadone interactions. METHODS: Among patients from a methadone
      clinic who received primary care from an affiliated, but separate, medical
      center, we reviewed electronic medical records for documentation of methadone,
      opioid dependence, and potential drug-methadone interactions. The proportions of
      medical records without opioid dependence and methadone documentation were
      estimated and potential medication-methadone interactions were identified.
      RESULTS: Among the study subjects (n = 84), opioid dependence documentation was
      missing from the medical record in 30% (95% CI, 20%-41%) and MMT documentation
      was missing from either the last primary care note or the last hospital discharge
      summary in 11% (95% CI, 5%-19%). Sixty-nine percent of the study subjects had at
      least 1 medication that potentially interacted with methadone; 19% had 3 or more
      potentially interacting medications. CONCLUSION: Among patients receiving MMT and
      medical care at different sites, documentation of opioid dependence and MMT in
      the medical record occurs for the majority, but is missing in a substantial
      number of patients. Most of these patients are prescribed medications that
      potentially interact with methadone. This study highlights opportunities for
      improved coordination between medical care and MMT.

PMID- 19578821
TI  - Simvastatin improves wound strength after intestinal anastomosis in the rat.
AB  - BACKGROUND: Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitor commonly known as a cholesterol-lowering drug with additional
      pleiotropic effects. Also, it is demonstrated that it prevents postoperative
      peritoneal adhesions in rat. This study was designed to assess its effects on the
      healing process of colonic anastomosis. METHODS: Thirty-two male Wistar albino
      rats were randomized into two groups and subjected to colonic anastomosis. The
      study group was treated with simvastatin and the control group received only tap
      water instead. The rats were killed 3 and 7 days postoperatively. Wound
      complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were
      recorded. Four types of assessment were performed: bursting pressure,
      hydroxyproline content, histopathology, and biochemical analysis. RESULTS:
      Compared to the control group, simvastatin-treated rats displayed a higher
      bursting pressure (p < 0.001) and anastomotic hydroxyproline content (p < 0.05).
      Simvastatin treatment leads to a significant decrease in malondealdehyde levels
      (p < 0.05) and increase in paraoxonase activity (p < 0.001) at both time points.
      Histopathological analysis revealed that simvastatin administration leads to a
      better anastomotic healing in terms of reepithelialization, decreased granuloma
      formation, reduced ischemic necrosis, and inflammatory infiltration to muscle
      layer. CONCLUSION: Clinically relevant doses of simvastatin do not have a
      negative impact on colonic anastomosis but improve intestinal wound healing in
      rats.

PMID- 19578822
TI  - Therapeutic effect of organic gallium on ovariectomized osteopenic rats by
      decreased serum minerals and increased bone mineral content.
AB  - The purpose of this study was to verify the effect of organic gallium on
      ovariectomized osteopenic rats. Thirty Wistar female rats used were divided into
      three groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats
      with osteopenia, and (3) OVX rats with osteopenia treated with organic gallium.
      Treatments were performed over an 8-week period. At sacrifice, the fifth lumbar
      vertebral body, one tibia, one femur, and the fourth lumbar vertebrae were
      removed, subjected to micro-CT for determination of trabecular bone structure,
      and then processed for histomorphometry to assess bone turnover. The femoral neck
      was used for mechanical compression testing. Treatment with organic gallium
      increased bone volume in OVX animals. Organic gallium-treated animals had
      significant increases in trabecular and cortical thickness and bone strength. The
      plasma total calcium and inorganic phosphate concentrations in OVX rats decreased
      and bone mineral content in the lumbar vertebrae and femur increased after
      treatment with organic gallium. These data provide an important proof of concept
      that organic gallium may represent a powerful approach to treating or reversing
      severe osteoporosis in humans.

PMID- 19578823
TI  - An experimental study of the effect of strontium pre-treatment on calcium release
      from carious and non-carious teeth.
AB  - The administration of strontium salt is known to be beneficial for bones in
      preventing calcium loss and osteoporosis. Therefore, we decided to study if
      strontium treatment affects calcium release from teeth in vitro. Extracted
      carious as well as non-carious teeth were washed, cleaned, and dried. These were
      individually immersed in 25 ml of 1% lactic acid at 37 degrees C for 24 h, and
      the amount of calcium released was measured. The rate of calcium release from
      these teeth was again determined after their exposure to M/4 strontium chloride
      for 1 month at 37 degrees C. It was found that: (1) the rate of calcium release
      from non-carious teeth was significantly higher than carious teeth, possibly
      because there was more calcium present, (2) the rate of calcium release was
      almost halved after strontium treatment in both groups of teeth, (3) the Vicker's
      microhardness of non-carious teeth was higher than those of carious teeth, and
      (4) strontium treatment did not affect hardness. Strontium treatment may be
      beneficial in reducing loss of calcium from intact teeth-non-carious as well as
      carious-and this beneficial effect of strontium is unrelated to change in teeth
      hardness.

PMID- 19578824
TI  - [Thromboembolism and pulmonary hypertension].
AB  - Chronic thrombembolic pulmonary hypertension (CTEPH) represents a common type of
      pulmonary hypertension and is associated with significant morbidity and
      mortality. The prognosis of this condition reflects the degree of associated
      right ventricular dysfunction. Unresolved thrombemboli and possible in situ
      thrombosis lead to obstruction of pulmonary arteries resulting in elevated
      pressures in those areas of the vasculature that were spared from thromboembolic
      occlusion. This can resemble pathomechanisms in patients with pulmonary arterial
      hypertension. However the understanding of pulmonary vascular remodeling in
      patients with CTEPH is incomplete. Pulmonary endarterectomy of the obstructing
      thromboembolic material should be performed in patients who are accessible to
      surgery. In patients who are judged inoperable or with persistent pulmonary
      hypertension treatment with pulmonary arterial hypertension medications can be
      considered. This could contribute to improved clinical outcome and survival,
      whereas further controlled studies are required addressing this question.

PMID- 19578825
TI  - Hibernation and daily torpor minimize mammalian extinctions.
AB  - Small mammals appear to be less vulnerable to extinction than large species, but
      the underlying reasons are poorly understood. Here, we provide evidence that
      almost all (93.5%) of 61 recently extinct mammal species were homeothermic,
      maintaining a constant high body temperature and thus energy expenditure, which
      demands a high intake of food, long foraging times, and thus exposure to
      predators. In contrast, only 6.5% of extinct mammals were likely heterothermic
      and employed multi-day torpor (hibernation) or daily torpor, even though torpor
      is widespread within more than half of all mammalian orders. Torpor is
      characterized by substantial reductions of body temperature and energy
      expenditure and enhances survival during adverse conditions by minimizing food
      and water requirements, and consequently reduces foraging requirements and
      exposure to predators. Moreover, because life span is generally longer in
      heterothermic mammals than in related homeotherms, heterotherms can employ a 'sit
      and-wait' strategy to withstand adverse periods and then repopulate when
      circumstances improve. Thus, torpor is a crucial but hitherto unappreciated
      attribute of small mammals for avoiding extinction. Many opportunistic
      heterothermic species, because of their plastic energetic requirements, may also
      stand a better chance of future survival than homeothermic species in the face of
      greater climatic extremes and changes in environmental conditions caused by
      global warming.

PMID- 19578826
TI  - Recilia banda Kramer (Hemiptera: Cicadellidae), a vector of Napier stunt
      phytoplasma in Kenya.
AB  - Napier grass (Pennisetum purpureum) is the most important fodder crop in
      smallholder dairy production systems in East Africa, characterized by small zero
      grazing units. It is also an important trap crop used in the management of cereal
      stemborers in maize in the region. However, production of Napier grass in the
      region is severely constrained by Napier stunt disease. The etiology of the
      disease is known to be a phytoplasma, 16SrXI strain. However, the putative insect
      vector was yet unknown. We sampled and identified five leafhopper and three
      planthopper species associated with Napier grass and used them as candidates in
      pathogen transmission experiments. Polymerase chain reaction (PCR), based on the
      highly conserved 16S gene, primed by P1/P6-R16F2n/R16R2 nested primer sets was
      used to diagnose phytoplasma on test plants and insects, before and after
      transmission experiments. Healthy plants were exposed for 60 days to insects that
      had fed on diseased plants and acquired phytoplasma. The plants were then
      incubated for another 30 days. Nested PCR analyses showed that 58.3% of plants
      exposed to Recilia banda Kramer (Hemiptera: Cicadellidae) were positive for
      phytoplasma and developed characteristic stunt disease symptoms while 60% of R.
      banda insect samples were similarly phytoplasma positive. We compared the
      nucleotide sequences of the phytoplasma isolated from R. banda, Napier grass on
      which these insects were fed, and Napier grass infected by R. banda, and found
      them to be virtually identical. The results confirm that R. banda transmits
      Napier stunt phytoplasma in western Kenya, and may be the key vector of Napier
      stunt disease in this region.

PMID- 19578827
TI  - Biotransformations of (+/-)-geosmin by terpene-degrading bacteria.
AB  - Two terpene-degrading bacteria able to transform (+/-)-geosmin have been
      identified. Pseudomonas sp. SBR3-tpnb, following growth on gamma-terpinene,
      converts (+/-)-geosmin to several products; the major products are ketogeosmins.
      Rhodococcus wratislaviensis DLC-cam, isolated on D-camphor, also converts (+/-)
      geosmin to several oxidation products, primarily ketogeosmins identical to those
      produced by strain SBR3-tpnb as well as hydroxygeosmins. This conversion appears
      to be inducible by (+/-)-geosmin and not by D-camphor.

PMID- 19578828
TI  - High-rate nitrogen removal from livestock manure digester liquor by combined
      partial nitritation-anammox process.
AB  - In this study, combination of a partial nitritation reactor, using immobilized
      polyethylene glycol (PEG) gel carriers, and a continuous stirred granular anammox
      reactor was investigated for nitrogen removal from livestock manure digester
      liquor. Successful nitrite accumulation in the partial nitritation reactor was
      observed as the nitrite production rate reached 2.1 kg-N/m(3)/day under aerobic
      nitrogen loading rate of 3.8 kg-N/m(3)/day. Simultaneously, relatively high free
      ammonia concentrations (average 50 mg-NH(3)/l) depressed the activity of nitrite
      oxidizing bacteria with nitrate concentration never exceeding 3% of TN
      concentration in the effluent of the partial nitritation reactor (maximum 35.2
      mg/l). High nitrogen removal rates were achieved in the granular anammox reactor
      with the highest removal rate being 3.12 kg-N/m(3)/day under anaerobic nitrogen
      loading rate of 4.1 kg-N/m(3)/day. Recalcitrant organic compounds in the digester
      liquor did not impair anammox reaction and the SS accumulation in the granular
      anammox reactor was minimal. The results of this study demonstrated that partial
      nitritation-anammox combination has the potential to successfully remove nitrogen
      from livestock manure digester liquor.

PMID- 19578829
TI  - Gene-specific markers for the wheat gene Lr34/Yr18/Pm38 which confers resistance
      to multiple fungal pathogens.
AB  - The locus Lr34/Yr18/Pm38 confers partial and durable resistance against the
      devastating fungal pathogens leaf rust, stripe rust, and powdery mildew. In
      previous studies, this broad-spectrum resistance was shown to be controlled by a
      single gene which encodes a putative ATP-binding cassette transporter. Alleles of
      resistant and susceptible cultivars differed by only three sequence polymorphisms
      and the same resistance haplotype was found in the three independent breeding
      lineages of Lr34/Yr18/Pm38. Hence, we used these conserved sequence polymorphisms
      as templates to develop diagnostic molecular markers that will assist selection
      for durable multi-pathogen resistance in breeding programs. Five allele-specific
      markers (cssfr1-cssfr5) were developed based on a 3 bp deletion in exon 11 of the
      Lr34-gene, and one marker (cssfr6) was derived from a single nucleotide
      polymorphism in exon 12. Validation of reference genotypes, well characterized
      for the presence or absence of the Lr34/Yr18/Pm38 resistance locus, demonstrated
      perfect diagnostic values for the newly developed markers. By testing the new
      markers on a larger set of wheat cultivars, a third Lr34 haplotype, not described
      so far, was discovered in some European winter wheat and spelt material. Some
      cultivars with uncertain Lr34 status were re-assessed using the newly derived
      markers. Unambiguous identification of the Lr34 gene aided by the new markers has
      revealed that some wheat cultivars incorrectly postulated as having Lr34 may
      possess as yet uncharacterised loci for adult plant leaf and stripe rust
      resistance.

PMID- 19578830
TI  - Estimating maize genetic erosion in modernized smallholder agriculture.
AB  - Replacement of crop landraces by modern varieties is thought to cause diversity
      loss. We studied genetic erosion in maize within a model system; modernized
      smallholder agriculture in southern Mexico. The local seed supply was described
      through interviews and in situ seed collection. In spite of the dominance of
      commercial seed, the informal seed system was found to persist. True landraces
      were rare and most informal seed was derived from modern varieties (creolized).
      Seed lots were characterized for agronomical traits and molecular markers. We
      avoided the problem of non-consistent nomenclature by taking individual seed lots
      as the basis for diversity inference. We defined diversity as the weighted
      average distance between seed lots. Diversity was calculated for subsets of the
      seed supply to assess the impact of replacing traditional landraces with any of
      these subsets. Results were different for molecular markers, ear- and
      vegetative/flowering traits. Nonetheless, creolized varieties showed low
      diversity for all traits. These varieties were distinct from traditional
      landraces and little differentiated from their ancestral stocks. Although
      adoption of creolized maize into the informal seed system has lowered diversity
      as compared to traditional landraces, genetic erosion was moderated by the
      distinct features offered by modern varieties.

PMID- 19578831
TI  - High-resolution melting analysis of cDNA-derived PCR amplicons for rapid and cost
      effective identification of novel alleles in barley.
AB  - An original method has been established for the identification of novel alleles
      of eukaryotic translation initiation factor 4E (eIF4E) gene, which is required
      for resistance to agronomically important bymoviruses, in barley germplasm. This
      method involves scanning for sequence variations in cDNA-derived PCR amplicons
      using High-resolution melting (HRM) followed by direct Sanger sequencing of only
      those amplicons which were predicted to carry nucleotide changes. HRM is a
      simple, cost-effective, rapid and high-throughput assay, which so far has only
      been widely used in clinical pathology for molecular diagnostic of diseases and
      patient genotyping. Application of HRM allowed significant reduction in the
      amount of expensive Sanger sequencing required for allele mining in plants. The
      method described here involved an investigation of total cDNA rather than genomic
      DNA, thus permitting the analyses of shorter (up to 300-bp) and fewer overlapping
      amplicons to cover the coding sequence. This strategy further reduced the allele
      mining costs. The sensitivity and accuracy of HRM for predicting genotypes
      carrying a wide range of nucleotide polymorphisms in eIF4E approached 100%.
      Results of the current study are promising and suggest that this method could
      also potentially be applied to the discovery of superior alleles controlling
      other important traits in barley as well in other model and crop plant species.

PMID- 19578832
TI  - Diurnal variation of melatonin and cortisol is maintained in non-septic intensive
      care patients.
AB  - OBJECTIVE: To study the diurnal variation of melatonin and cortisol in critically
      ill patients and to assess whether the severity of organ dysfunction, sedation
      and sympathetic activity correlate with the production of these hormones. DESIGN:
      Prospective clinical study. SETTING: Surgical intensive care unit in a university
      hospital. PATIENTS: Forty non-septic patients without brain injury and treatment
      with adrenergic agonists or corticosteroids. Twenty-five of the patients were
      sedated with benzodiazepines. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The
      pattern of melatonin production was monitored by the determination of 6
      sulphatoxymelatonin (aMT6s) in urine. The 12-h aMT6s excretions at nights (11.8
      +/- 8.9 microg, mean +/- SD) were higher than in the daytime (6.8 +/- 7.5 microg;
      P < 0.0001), and benzodiazepine treatment did not abolish the diurnal periodicity
      of aMT6s excretion during the entire 3-day study period. Serum cortisol
      concentrations at noon (524 +/- 276 nmol/l, mean +/- SD) were higher than at
      midnight (415 +/- 172 nmol/l; P < 0.0001), and the decrease at midnight was
      significant also in the patients treated with benzodiazepines. Sympathetic
      activity was monitored with urine vanillylmandelic acid (VMA). The 12-h VMA
      excretions did not show a diurnal variation, but a significant positive
      relationship between the 12-h VMA and aMT6s excretions was observed. The severity
      of organ dysfunction did not correlate either with the aMT6s and VMA excretion or
      with serum cortisol concentration. CONCLUSIONS: The diurnal variation of
      melatonin and cortisol is maintained in non-septic intensive care unit patients.
      Benzodiazepines do not impair the diurnal variation of melatonin and cortisol.

PMID- 19578833
TI  - Determination of dimethyl fumarate and other potential allergens in desiccant and
      antimould sachets.
AB  - A method for the determination of dimethyl fumarate (DMF), benzothiazole (BT) and
      tert-butylphenol (TBP) in desiccant and antimould agents employed for protecting
      consumer products from humidity and mould has been developed. The method is based
      on ultrasound-assisted extraction (UAE) followed by GC-MS analysis. Parameters
      that could affect the extraction of the compounds have been optimised using a
      multivariate approach. In the final conditions, the extraction is performed using
      only 0.5 or 1 mL ethyl acetate and applying ultrasound energy for 5 min.
      Simultaneous extractions could also be carried out in 5 min without losing
      efficiency. The method was validated showing good linearity (R2 >0.995). Both
      intra- and inter-day precisions were studied at several concentration levels,
      being satisfactory in all cases (RSD <10%). Recovery was evaluated in four real
      desiccant samples at different compound concentrations, ranging between 87% and
      109%. Limits of detection and quantification were in the low nanogramme per
      gramme level, thus allowing the determination of DMF at concentrations well below
      the limit established by the recent EU Directive (0.1 microg/g). The proposed
      procedure was applied to the determination of the target compounds in several
      desiccant and antimould samples. Although most of them were simply labelled as
      "silica gel", more than 70% of the tested samples contained high amounts of DMF,
      many of them at the high microgram per gramme level. Many samples also showed the
      presence of the other two potential allergens. These results demonstrate that the
      content of the "desiccant" sachets and tablets in consumer products does not
      usually belong with the label of the desiccant, and hence, the high risk of
      exposition to the powerful allergen DMF and other potentially harmful chemicals
      through consumer goods should be a matter of concern.

PMID- 19578834
TI  - Dielectrophoresis for manipulation of micro/nano particles in microfluidic
      systems.
AB  - Dielectrophoretic (DEP) force is exerted when a neutral particle is polarized in
      a non-uniform electric field, and depends on the dielectric properties of the
      particle and the suspending medium. The integration of DEP and microfluidic
      systems offers numerous applications for the separation, trapping, assembling,
      transportation, and characterization of micro/nano particles. This article
      reviews the applications of DEP forces in microfluidic systems. It presents the
      theory of dielectrophoresis, different configurations, and the applications of
      such systems for particle manipulation and device fabrication.

PMID- 19578835
TI  - Gradient HPLC separation of dehydroepiandrosterone (DHEA) from its metabolites
      and biological congeners: role of tetrahydrofuran in the chromatographic
      mechanism.
AB  - A three-step gradient reversed-phase high-performance liquid chromatography (RP
      HPLC) method was developed for the separation of dehydroepiandrosterone (DHEA),
      its sulfate ester (DHEA-S), its three C7-oxidized metabolites (7alphaOH-DHEA,
      7betaOH-DHEA, 7-keto-DHEA), and its biosynthetic congeners (androstenedione,
      testosterone, estradiol, pregnenolone). This new method allows the quantitative
      characterization of DHEA metabolism and biosynthetic transformation under given
      physiological, pathological, or therapeutically influenced circumstances.
      Tetrahydrofuran probably acts as a proton acceptor coadsorbent, while isopropanol
      behaves as a proton donor during the separation of testosterone, estradiol, and
      the stereoisomers of 7-OH-DHEA.

PMID- 19578836
TI  - Molecular aspects of milk allergens and their role in clinical events.
AB  - Milk allergy is the most frequent food allergy in childhood. Even though cases of
      newly developed milk allergy in adulthood are known, this allergy is less
      frequent in adults since it is normally outgrown by children during the first
      years of life. One of the reasons why allergy to cow's milk shows its highest
      prevalence in children is its early introduction into the diets of babies when
      breast feeding is not possible. The major allergens are caseins and beta
      lactoglobulin, but allergies to other minor proteins (immunoglobulins, bovine
      serum albumin) have also been reported. Milk allergenicity can be reduced by
      various treatments (mainly hydrolysis), meaning that formulas based on cow's milk
      can often be safely fed to children allergic to milk proteins. Cross-reactivity
      has been described between different mammalian milks and between milk and meat or
      animal dander. Cross-contamination can result from inadequate cleaning of
      industrial equipment and constitutes a hidden danger for allergic subjects who
      unknowingly ingest milk proteins.

PMID- 19578837
TI  - Calibration-free concentration determination of charged colloidal nanoparticles
      and determination of effective charges by capillary isotachophoresis.
AB  - Although colloidal nanoparticles show an electrophoretic heterogeneity under the
      conditions of capillary electrophoresis, which can be either due to the particle
      size distribution and/or the particle shape distribution and/or the zeta
      potential distribution, they can form correct isotachophoretic zones with sharp
      moving boundaries. Therefore, the technique of isotachophoresis permits to
      generate plugs in which the co-ions and counter ions of the original colloidal
      solution are removed and replaced by the buffering counter ions of the leading
      electrolyte. It is shown that analytical isotachophoresis can be used to measure
      directly, without calibration, the molar (particle) concentration of dispersed
      ionic colloids provided that the transference number and the mean effective
      charge number of the particles (within the isotachophoretic zone) can be
      determined with adequate accuracy. The method can also be used to measure
      directly the effective charge number of biomacromolecules or colloidal particles,
      if solutions with known molar (particle) concentration can be prepared. The
      validity of the approach was confirmed for a model solution containing a known
      molar concentration of bovine serum albumin.

PMID- 19578838
TI  - Motor unit firing variability and synchronization during short-term light-load
      training in older adults.
AB  - We compared motor unit synchronization and firing rate variability within and
      across synergistic hand muscles during a pinching task following short-term light
      load training to improve force steadiness in older adults. A total of 183 motor
      unit pairs before training and 158 motor unit pairs after training were recorded
      with intramuscular fine-wire electrodes within and across the first dorsal
      interosseous (FDI) and adductor pollicis (AdP) muscles during a pinch task
      performed by ten older adults before and after a 4-week short-term light-load
      training program. Nine younger adults performed the same experimental sessions 4
      weeks apart with no training intervention. Two-minute sustained contractions of
      2, 4, 8, and 12% maximal voluntary contraction (MVC) were performed with the non
      dominant hand. The coefficient of variation (CV) of force was greater in older
      than in younger adults and was lower at the 2 and 4% MVC levels in both the
      finger (0.12 +/- 0.01 vs. 0.08 +/- 0.01, and 0.08 +/- 0.01 vs. 0.05 +/- 0.01,
      respectively) and thumb (0.11 +/- 0.01 vs. 0.08 +/- 0.01, and 0.09 +/- 0.01 vs.
      0.05 +/- 0.01, respectively) compared to higher force levels following training
      in the older adults. There were no changes in CIS or k'-1 values following
      training. Motor unit firing rate variability significantly decreased at low force
      levels in the FDI muscle and also tended to decrease with training in the AdP
      muscle (p = 0.06). No changes occurred in the younger control group. These
      findings are the first to show that motor unit synchronization does not change
      during light-load training. Thus, it is likely that force steadiness in older
      adults improves by reducing motor unit firing variability rather than by changing
      motor unit synchronization.

PMID- 19578839
TI  - The effects of bottom-up target luminance and top-down spatial target
      predictability on saccadic reaction times.
AB  - Saccadic reaction times (SRT) are composed of the sum of multiple processes,
      including bottom-up sensory processing, top-down goal oriented processing, and
      afferent and efferent conduction delays. In order to determine the timing
      dependencies and potential interactions between bottom-up and top-down processes
      on SRTs, we trained monkeys to perform several variants of visually guided
      saccade tasks. Bottom-up components of SRT were manipulated by varying target
      luminance from near detection threshold to supra-threshold ranges (i.e., 0.001
      42.5 cd/m(2)). There was a significant reduction of mean SRT with increases in
      target luminance up to 3.5-17.5 cd/m(2). Luminance increases above these ranges
      produced significant increases in SRT when the target was within 6 degrees from
      the fovea. Top-down components were assessed by manipulating spatial target
      predictability across blocks of trials using either 1, 2, 4 or 8 possible target
      locations. Decreasing spatial target predictability increased SRT across target
      luminances from 1 to 4 targets in the gap task, but then paradoxically decreased
      SRT again when there were 8 possible targets in both the gap and step tasks.
      Finally, a gap task (200 ms gap) was used to determine the dependence of target
      luminance on the magnitude of the gap effect. Decreasing target luminance
      significantly reduced the magnitude of the gap effect indicating that the gap
      effect is strongly influenced by bottom-up factors.

PMID- 19578840
TI  - Multiple timescales in postural dynamics associated with vision and a secondary
      task are revealed by wavelet analysis.
AB  - Discrete wavelet analysis is used to resolve the center of pressure time series
      data into several timescale components, providing new insights into postural
      control. Healthy young and elderly participants stood quietly with their eyes
      open or closed and either performed a secondary task or stood quietly. Without
      vision, both younger and older participants had reduced energy in the long
      timescales, supporting the concept that vision is used to control low frequency
      postural sway. Furthermore, energy was increased at timescales corresponding to
      closed-loop (somatosensory and vestibular) and open-loop mechanisms, consistent
      with the idea of a shift from visual control to other control mechanisms.
      However, a relatively greater increase was observed for older adults. With a
      secondary task a similar pattern was observed-increased energy at the short and
      moderate timescales, decreased energy at long timescales. The possibility of a
      common strategy-at the timescale level-in response to postural perturbations is
      considered.

PMID- 19578841
TI  - Angular momentum synergies during walking.
AB  - We studied the coordination of body segments during treadmill walking.
      Specifically, we used the uncontrolled manifold hypothesis framework to quantify
      the segmental angular momenta (SAM) synergies that stabilize (i.e., reduce the
      across trials variability) the whole body angular momentum (WBAM). Seven male
      subjects were asked to walk over a treadmill at their comfortable walking speed.
      A 17-segment model, fitted to the subject's anthropometry, was used to
      reconstruct their kinematics and to compute the SAM and WBAM in three dimensions.
      A principal component analysis was used to represent the 17 SAM by the magnitudes
      of the first five principal components. An index of synergy (DeltaV) was used to
      quantify the co-variations of these principal components with respect to their
      effect on the WBAM. Positive values of DeltaV were observed in the sagittal plane
      during the swing phase. They reflected the synergies among the SAM that
      stabilized (i.e., made reproducible from stride to stride) the WBAM. Negative
      values of DeltaV were observed in both frontal and sagittal plane during the
      double support phase. They were interpreted as "anti-synergies", i.e., a
      particular organization of the SAM used to adjust the WBAM. Based on these
      results, we demonstrated that the WBAM is a variable whose value is regulated by
      the CNS during walking activities, and that the nature of the WBAM control
      changed between swing phase and double support phase. These results can be linked
      with humanoid gait controls presently employed in robotics.

PMID- 19578842
TI  - Direct-puncture approach to the extraconal portion of the superior ophthalmic
      vein for carotid cavernous fistulae.
AB  - INTRODUCTION: The transvenous approach via the superior ophthalmic vein (SOV) is
      an available approach for carotid cavernous fistula (CCF), especially in the
      event that there is no other suitable approach route to the fistula. Surgical
      exposure of the peripheral roots of the SOV is commonly used; however, often, the
      SOV is often not accessible because of anatomical problems and/or complications.
      In this paper, we present and discuss our original direct-puncture approach to
      the extraconal portion of the SOV. METHODS: An attempt on three patients with
      traumatic CCF failed with the transarterial approach and the conventional venous
      approach via the inferior petrosal sinus; therefore, the patients were treated
      with the direct-puncture approach to the extraconal portion of the SOV using two
      dimensional digital subtraction angiography with local anesthesia. RESULTS: All
      cases that had tortuous and partially stenotic division of the SOV were treated
      successfully with this approach and without complications. CONCLUSION: This
      approach will become an alternate approach, especially when the peripheral roots
      of the SOV are focally narrowed and tortuous, making it impossible to insert a
      catheter.

PMID- 19578843
TI  - Production of individual ganoderic acids and expression of biosynthetic genes in
      liquid static and shaking cultures of Ganoderma lucidum.
AB  - Two-stage culture was efficient in enhancing total ganoderic acid (GA) production
      by Ganoderma lucidum (Fang and Zhong, Biotechnol Prog 18:51-54, 2002). As
      different GAs have different bioactivities, it is critical to understand the
      kinetics of individual GA production during fermentation, but no related
      information is yet available. To understand the regulation of GA biosynthesis,
      investigation of the accumulation of intermediate (lanosterol) and by-product
      (ergosterol) and of the expression of three important biosynthetic genes was also
      conducted in liquid shaking and static cultures of G. lucidum. The results showed
      that the content of individual GAs increased rapidly in the liquid static
      culture, and their maximum value was 6- to 25-fold that of shaking culture while
      lanosterol content in the former was lower than the latter. The transcript of
      squalene synthase (SQS), lanosterol synthase and 3-hydroxy-3-methylglutaryl
      coenzyme A reductase in liquid static culture was 4.3-, 2.1-, and 1.9-fold that
      of the shaking culture, respectively. Higher GA content in liquid static culture
      was related to increased transcription of those genes especially SQS. The work is
      helpful to the production of individual GAs and provided an insight into why the
      liquid static culture was superior to the shaking culture in view of biosynthetic
      gene expression.

PMID- 19578844
TI  - Sequence-specific bacterial growth inhibition by peptide nucleic acid targeted to
      the mRNA binding site of 16S rRNA.
AB  - Peptide nucleic acid (PNA) targeted to the functional domains of 23S rRNA can
      inhibit translation and cell growth. However, effective inhibition of translation
      and cell growth using 16S rRNA-targeted PNA has still not been achieved. Here, we
      report that PNA targeted to the functional site of 16S rRNA could inhibit both
      gene expression in vitro and bacterial growth in pure culture with sequence
      specificity. We used 10-mer PNAs conjugated with a cell-penetrating peptide,
      which targeted the mRNA binding site at the 3' end of 16S rRNA. Using 0.6 microM
      of the peptide-PNAs, cell-free ss-galactosidase production decreased by 50%,
      whereas peptide-PNAs with one or two mismatches to the target sequence showed
      much weaker inhibition effects. To determine the growth inhibition and
      bactericidal effects of the peptide-PNA conjugate, we performed OD measurement
      and viable cell counting. We observed dose- and sequence-dependent inhibition of
      cell growth and bactericidal effects. These growth inhibitory effects are
      observed both in the Gram-negative bacterium of Escherichia coli and the Gram
      positive bacteria Bacillus subtilis and Corynebacterium efficiens, although
      inhibitory concentrations were different for each bacterial species. These
      results present possibilities for 16S rRNA sequence-based specific bacterial
      growth inhibition using a peptide-PNA conjugate.

PMID- 19578845
TI  - Biotransformation of steriodal saponins in Dioscorea zingiberensis C. H. Wright
      to diosgenin by Trichoderma harzianum.
AB  - Diosgenin is an important starting material in the steroidal hormone industry.
      Traditionally, diosgenin is mainly produced by acid hydrolysis of Dioscorea
      zingiberensis C. H. Wright (DZW) tubers. This method yields numerous byproducts
      that can cause serious pollution. In this study, diosgenin was obtained by
      biotransformation of steroidal saponins in DZW afforded by Trichoderma harzianum
      CGMCC 2979. The medium was optimized for maximum diosgenin production. The
      addition of phosphate buffer, surfactant Tween-85, and Fe(2+) increased the yield
      of diosgenin by 50.28%, 33.35%, and 22.07%, respectively. The optimum medium
      obtained by response surface methodology was composed of 60 mmol l(-1) phosphate
      buffer, 0.07% (w/v) Tween-85, and 0.93 mmol l(-1) Fe(2+). Under these conditions,
      a maximum diosgenin yield of 30.05 +/- 0.59 mg g(-1) was achieved, which was
      slightly higher than that obtained from traditional acid hydrolysis. By
      hydrolyzing the un-transformed steroidal saponins after biotransformation, the
      total diosgenin yield increased by 35% compared to traditional method. Moreover,
      chemical oxygen demand and residual reduced sugar in the wastewater produced by
      this integrated process were only 3.72% and 0.3%, respectively, that of the
      traditional acid hydrolysis method.

PMID- 19578846
TI  - Bioremediation of the organochlorine pesticides, dieldrin and endrin, and their
      occurrence in the environment.
AB  - Dieldrin and endrin are persistent organic pollutants that cause serious
      environmental problems. Although these compounds have been prohibited over the
      past decades in most countries around the world, they are still routinely found
      in the environment, especially in the soil in agricultural fields.
      Bioremediation, including phytoremediation and rhizoremediation, is expected to
      be a useful cleanup method for this soil contamination. This review provides an
      overview of the environmental contamination by dieldrin and endrin, along with a
      summary of our current understanding and recent advances in bioremediation and
      phytoremediation of these pollutants. In particular, this review focuses on the
      types and abilities of plants and microorganisms available for accumulating and
      degrading dieldrin and endrin.

PMID- 19578847
TI  - Recent advances in the biological production of mannitol.
AB  - Mannitol is a fructose-derived, 6-carbon sugar alcohol that is widely found in
      bacteria, yeasts, fungi, and plants. Because of its desirable properties,
      mannitol has many applications in pharmaceutical products, in the food industry,
      and in medicine. The current mannitol chemical manufacturing process yields
      crystalline mannitol in yields below 20 mol% from 50% glucose/50% fructose
      syrups. Thus, microbial and enzymatic mannitol manufacturing methods have been
      actively investigated, in particular in the last 10 years. This review summarizes
      the most recent advances in biological mannitol production, including the
      development of bacterial-, yeast-, and enzyme-based transformations.

PMID- 19578848
TI  - Efficacy of rituximab in autoimmune hemolytic anemia associated with splenic
      marginal zone lymphoma.

PMID- 19578849
TI  - Differential effects of interleukin-12 and interleukin-15 on expansion of NK cell
      receptor-expressing CD8+ T cells.
AB  - The cytolytic activity of cells expressing natural killer cell receptors (NKRs)
      depends on the balance between stimulatory and inhibitory signals. We
      investigated both inhibitory NK receptor (CD94/NKG2A) expression and stimulatory
      NKR (NKG2D) expression on T cells after stimulation with cytokines (IL-12 or IL
      15). Cytolytic NKR-expressing CD8(+) T cells were expanded from normal adult
      peripheral blood mononuclear cells using anti-CD3 monoclonal antibody and
      cytokines (IL-12 or IL-15). The proportion and absolute number of CD94/NKG2A
      expressing T cells expanded by IL-12 were significantly larger than those of the
      cells expanded by IL-15. On the other hand, the proportion and absolute number of
      NKG2D-expressing T cells expanded by IL-15 were significantly larger than those
      of the cells expanded by IL-12. The proportions of NKG2D and intracellular
      granzyme A expression in CD94-expressing cells were much more increased in PBMCs
      cultured with IL-15 than those of cells cultured with IL-12. A real-time
      polymerase chain reaction assay showed that there was a 1.68-fold increase in
      NKG2D mRNA expression level and a 1.37-fold increase in DAP10 mRNA expression
      level in CD94-expressing cells expanded by IL-15 compared with those of the cells
      expanded by IL-12. The cytolytic activity levels of purified CD94-expressing
      cells from 8-day culture with IL-15 tested against (51)Cr-labeled K562 cells by
      standard 4-h (51)Cr release assays without prior sensitization were much higher
      than those of cells from 8-day culture with IL-12. IL-15 appears to be able to
      enhance the cytolytic activity of CD94/NKG2A-expressing cells through induction
      of NKG2D and intracellular granzyme expression much more efficiently than does IL
      12.

PMID- 19578850
TI  - A multicenter phase II study of gemcitabine and S-1 combination chemotherapy in
      patients with unresectable pancreatic cancer.
AB  - PURPOSE: To confirm the efficacy and toxicity of gemcitabine and S-1 combination
      chemotherapy when used as a first-line therapy in patients with unresectable
      pancreatic cancer. METHODS: Patients with locally advanced or metastatic or
      recurrent pancreatic adenocarcinoma, which was histologically or cytologically
      proven, with at least one measurable lesion were eligible for the study.
      Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days
      1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1
      to 14, and the cycle was repeated every 3 weeks. The objective response rate,
      which was assessed according to RECIST criteria, was the primary end point.
      RESULTS: A total of 38 patients were enrolled between June 2006 and June 2007.
      The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients
      were evaluable for response. Although no complete response was seen, partial
      responses were achieved in 11 patients, resulting in an overall response rate of
      32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0
      months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months
      (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI
      5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia
      (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The
      major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis
      (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%). CONCLUSIONS:
      Gemcitabine and S-1 combination chemotherapy was effective and tolerable in
      patients with unresectable pancreatic cancer.

PMID- 19578851
TI  - A case of primary Sjogren's syndrome with pulmonary-limited Wegener's
      granulomatosis.
AB  - A 60-year-old woman had a history of dyspnea for 5-6 weeks. The chest radiograph
      and computed tomography scans revealed bilateral patchy reticulonodular pattern.
      The patient had positive test results for antineutrophil cytoplasmic antibody
      against proteinase-3 (c-ANCA), antinuclear antibody and anti-Ro antibody.
      According to European Study Group on Classification Criteria for Sjogren's
      Syndrome, the patient was diagnosed as primary Sjogren's syndrome based on the
      presence of clinical features, positive findings on Schirmer's test and parotis
      scintigraphy. Lung biopsy obtained by wedge resection showed granulomatous
      inflammation with extensive multinuclear giant cells involving the lung
      parenchyma and vascular structures. There was neither upper airway nor renal
      involvement. Thus, the patient was simultaneously diagnosed as pulmonary-limited
      Wegener's granulomatosis. With this unique case, we would like to emphasize that
      the awareness of ANCA-associated vasculitis as a diagnostic possibility in
      primary Sjogren's syndrome is important during the work-up of lung lesions.

PMID- 19578852
TI  - Prevalence of positive ppd in a cohort of rheumatoid arthritis patients.
AB  - The main objective of this study is to determine the prevalence of positive and
      anergic tuberculin skin test (ppd) in a rheumatoid arthritis cohort of patients
      (RA) and assess the association among ppd results and clinical and treatment
      variables. Patients with RA diagnosis were included. The ppd was done by Mantoux
      method. Positive result was considered when indurations were equal or greater
      than 5 mm. Anergic reaction was defined when the indurations was 0 mm. We
      included 105 patients (N = 105). The prevalence of positive ppd was 12.4% (n =
      13), while the 87.6% (n = 92) presented a negative result. The 69.5% (n = 73) of
      the population were anergic to ppd. Patients with negative result received higher
      steroids dosages than patients with positive ppd (p < 0.04). In the multivariable
      model, the steroids dosage was a significant and independent predictor of
      negative ppd (p = 0.021, OR 0.72, 95% CI 0.55-0.95). Anergic and non-anergic
      patients were separated in groups, and a new analysis was done. The higher dosage
      of methotrexate was associated to tuberculine anergy (p = 0.025). In the
      multivariable model, the methotrexate dosage was a significant and independent
      predictor of tuberculine anergy (p = 0.005, OR 1.14, 95% CIs 1.04-1.24). In
      conclusion, in our cohort, the prevalence of positive ppd was lower than others
      studies. Among analyzed variables, the high steroid dose was a significant and
      independent predictor of negative ppd. The methotrexate treatment and dose were
      associated with ppd anergy.

PMID- 19578853
TI  - Erdheim-Chester disease: a pitfall in DXA measurements.

PMID- 19578854
TI  - Phenotypic and molecular evaluation of cotton hairy roots as a model system for
      studying nematode resistance.
AB  - Agrobacterium rhizogenes-induced cotton (Gossypium hirsutum L.) hairy roots were
      evaluated as a model system for studying molecular cotton-nematode interactions.
      Hairy root cultures were developed from the root-knot nematode (RKN) (Meloidogyne
      incognita [Kofoid and White] Chitwood, race 3)-resistant breeding line M315 and
      from the reniform nematode (RN) (Rotylenchulus reniformis Linford & Oliveira)
      resistant accession GB713 (G. barbadense L.) and compared to a nematode
      susceptible culture derived from the obsolete cultivar DPL90. M315, GB713, and
      DPL90 hairy roots differed significantly in their appearance and growth
      potential; however, these differences were not correlated with transcript levels
      of the A. rhizogenes T-DNA genes rolB and aux2 which help regulate hairy root
      initiation and proliferation. DPL90 hairy roots were found to support both RKN
      and RN reproduction in tissue culture, whereas M315 and GB713 hairy roots were
      resistant to RKN and RN, respectively. M315 hairy roots showed constitutive up
      regulation of the defense gene MIC3 (Meloidogyne Induced Cotton3) compared to
      M315 whole-plant roots and DPL90 hairy roots. Our data show the potential use of
      cotton hairy roots in maintaining monoxenic RKN and RN cultures and suggest hairy
      roots may be useful in evaluating the effect of manipulated host gene expression
      on nematode resistance in cotton.

PMID- 19578855
TI  - Sexually mature transgenic American chestnut trees via embryogenic suspension
      based transformation.
AB  - The availability of a system for direct transfer of anti-fungal candidate genes
      into American chestnut (Castanea dentata), devastated by a fungal blight in the
      last century, would offer an alternative or supplemental approach to conventional
      breeding for production of chestnut trees resistant to the blight fungus and
      other pathogens. By taking advantage of the strong ability of embryogenic
      American chestnut cultures to proliferate in suspension, a high-throughput
      Agrobacterium tumefaciens-mediated transformation protocol for stable integration
      of foreign genes into the tree was established. Proembryogenic masses (PEMs) were
      co-cultivated with A. tumefaciens strain AGL1 harboring the plasmid pCAMBIA 2301,
      followed by stringent selection with 50 or 100 mg/l Geneticin. A protocol
      employing size-fractionation to enrich for small PEMs to use as target material
      and selection in suspension culture was applied to rapidly produce transgenic
      events with an average efficiency of four independent transformation events per
      50 mg of target tissue and minimal escapes. Mature somatic embryos, representing
      18 transgenic events and derived from multiple American chestnut target
      genotypes, were germinated and over 100 transgenic somatic seedlings were
      produced and acclimatized to greenhouse conditions. Multiple vigorous transgenic
      somatic seedlings produced functional staminate flowers within 3 years following
      regeneration.

PMID- 19578856
TI  - Laparoscopic ureteral reimplantation: prospective evaluation of medium-term
      results and current developments.
AB  - OBJECTIVE: Laparoscopic ureteral reimplantation is a feasible method for treating
      ureteral pathology with good preliminary results in the literature. In this
      study, we review our medium-term results for laparoscopic ureteral reimplantation
      and discuss current developments of this procedure. MATERIALS AND METHODS: Twenty
      four laparoscopic ureteral reimplantations were performed between August 2003 and
      December 2008 for ureteral strictures or ureteral injuries. The mean age was 53.5
      years (8 men, 16 women). Patient demographics, preoperative symptoms,
      radiological imaging, complications, and postoperative outcomes were analyzed.
      Ten patients underwent vesicopsoas-hitch, nine patients had a vesicopsoas-hitch
      combined with Boari-flap, and five had Lich-Gregoir extravesical ureteral
      reimplantations. Success was defined as relief of obstruction on postoperative
      imaging studies, as well as symptomatic relief. RESULTS: Laparoscopic ureteral
      reimplantations were successfully performed in all patients. The mean operative
      time was 215 min (131-351). Mean estimated blood loss was 283 ml (50-550). One
      patient had an intraoperative bowel injury which was managed laparoscopically
      during the same procedure. There were two postoperative complications; two
      prolonged ileus and one deep venous thrombosis (DVT). Mean hospital stay was 8.7
      days. Average time to return to normal activity was 2.6 weeks. Postoperative
      radiological imaging studies showed good drainage, without hydronephrosis, in 23
      patients (success rate 95.8 %) at a median follow up interval of 35 months.
      CONCLUSIONS: Laparoscopic ureteral reimplantation is an effective procedure with
      good medium-term results. We believe that this procedure will become an
      established treatment option.

PMID- 19578857
TI  - [Anterior surface breakdown following evisceration : "Classic", "scleral
      modification", and "scleral patch techniques"].
AB  - BACKGROUND: To evaluate the frequency of anterior surface breakdown for three
      techniques of evisceration with primary implant placement: the "classic"
      technique, the "scleral modification" technique, and the novel "scleral patch"
      technique. METHODS: Retrospective comparative case series with 73 consecutive
      eviscerations with primary implants that were performed in the Eye Clinic
      Rotterdam between January 2003 and January 2007. RESULTS: The operations involved
      the classic technique for 55% of the patients, scleral modification for 29%, and
      the novel scleral patch technique for 16%. In all, 9.6% of the patients had
      conjunctival breakdown: six in the classic group and one in the patch group.
      Although the frequency of this complication was higher in the classic group, the
      difference was not significant (P>0.05, chi-square test). Anterior surface
      breakdown was not related to implant size or prior eye surgery. CONCLUSION:
      Compared with the scleral modification and scleral patch techniques, conjunctival
      breakdown and implant extrusion were seen more frequently after classic
      evisceration with implant placement. Implant size or indication for surgery were
      not related to the frequency of these complications.

PMID- 19578858
TI  - Lifetime- and caste-specific changes in flight metabolic rate and muscle
      biochemistry of honeybees, Apis mellifera.
AB  - Honeybees, Apis mellifera, who show temporal polyethism, begin their adult life
      performing tasks inside the hive (hive bees) and then switch to foraging when
      they are about 2-3 weeks old (foragers). Usually hive tasks require little or no
      flying, whereas foraging involves flying for several hours a day and carrying
      heavy loads of nectar and pollen. Flight muscles are particularly plastic organs
      that can respond to use and disuse, and accordingly it would be expected that
      adjustments in flight muscle metabolism occur throughout a bee's life. We thus
      investigated changes in lifetime flight metabolic rate and flight muscle
      biochemistry of differently aged hive bees and of foragers with varying foraging
      experience. Rapid increases in flight metabolic rates early in life coincided
      with a switch in troponin T isoforms and increases in flight muscle maximal
      activities (V (max)) of the enzymes citrate synthase, cytochrome c oxidase,
      hexokinase, phosphofructokinase, and pyruvate kinase. However, further increases
      in flight metabolic rate in experienced foragers occurred without additional
      changes in the in vitro V (max) of these flight muscle metabolic enzymes.
      Estimates of in vivo flux (v) compared to maximum flux of each enzyme in vitro
      (fractional velocity, v/V (max)) suggest that most enzymes operate at a higher
      fraction of V (max) in mature foragers compared to young hive bees. Our results
      indicate that honeybees develop most of their flight muscle metabolic machinery
      early in life. Any further increases in flight metabolism with age or foraging
      experience are most likely achieved by operating metabolic enzymes closer to
      their maximal flux capacity.

PMID- 19578859
TI  - Effect of pectin feeding on monocarboxylate transporters in rat adrenal gland.
AB  - We have recently proved the expression and localization of seven monocarboxylate
      transporters (MCT1, MCT2, MCT3, MCT4, MCT5, MCT7, and MCT8) in the rat adrenal
      gland. So far, there are no data reporting possible regulation of any MCT isoform
      in the adrenal gland. Pectin is a soluble dietary fiber that is known to exert a
      hypocholesterolemic effect and increases the short chain fatty acids production
      in the large intestine. This work aimed to study the effect of pectin feeding on
      the expression of MCTs (MCT1-MCT5, MCT7, and MCT8) and their cellular
      distribution in rat adrenal gland. Western blotting demonstrated significant
      increase in the expression levels of MCT1, MCT2, MCT4, MCT5, and MCT7 in pectin
      fed rats in comparison with the controls. Immunohistochemistry revealed extended
      distribution and distinctive increase in the immunoreactivities of MCT1, MCT2,
      MCT4, MCT5, and MCT7 in the adrenal cortical zones, besides the increase in the
      immunoreactive intensity of MCT5 and MCT7 in the adrenal medulla of pectin-fed
      versus control rats. Interestingly, zona glomerulosa which did not show any
      reactivity for MCT1 or MCT2 in controls, exhibited marked immunopositivities for
      both MCT1 and MCT2 in pectin-fed rats. MCT3 and MCT8, however, did not show
      significant changes in their expression levels between pectin-fed and control
      rats. Our data is the first to describe the up regulation of various MCTs in rat
      adrenal gland under the influence of pectin feeding. This up regulation might be
      a compensatory response to the hypocholesterolemic effect of pectin in order to
      maximize the intracellular availability of acetate. This article suggests that
      monocarboxylate transporters have an important physiological role in the
      regulation of adrenal hormones as well as in cholesterol homeostasis.

PMID- 19578860
TI  - Anterior fundoplication at the time of congenital diaphragmatic hernia repair.
AB  - PURPOSE: The loss of normal anatomic barriers in neonates with congenital
      diaphragmatic hernia (CDH) can predispose children to gastroesophageal reflux
      (GER). In an attempt to improve post-operative feeding, we have added a modified
      anterior fundoplication to restore natural gastric and esophageal positioning.
      METHODS: The institutional review board of both participating centers approved
      this study. Between 1997 and 2008, 13 neonates with high-risk anatomy underwent
      repair of CDH combined with an anterior fundoplication (Boix-Ochoa). The anatomic
      indications for concomitant fundoplication were absence of an intra-abdominal
      esophagus, an obtuse angle of His, and a small, vertically oriented stomach.
      RESULTS: Ten patients survived to discharge and eight were on full oral
      nourishment. One required partial gastrostomy feedings for an improving oral
      aversion and quickly progressed to full oral feedings. One patient with
      chromosomal anomalies and swallowing dysfunction remained on long-term bolus
      gastrostomy feedings. Two with progressive symptoms of GER and failure to thrive
      required conversion to a 360 degrees wrap after 18 months of medical management.
      This was performed in conjunction with a planned, staged muscle flap
      reconstruction in one patient. There were no complications related to the
      fundoplication. CONCLUSION: Anatomic predictors of severe GER can be efficiently
      countered at the time of CDH repair. A modified fundoplication should be
      considered in the operative management of high-risk infants.

PMID- 19578861
TI  - [Antibodies against citrullinated peptides in clinical practice and research].
AB  - Since their original description ten years ago, antibodies against citrullinated
      peptide antigens (ACPA) have become increasingly important in the diagnosis of
      rheumatoid arthritis (RA). They are now considered superior to the rheumatoid
      factor because they can be detected earlier in the course of the disease and are
      more specific while showing a comparable sensitivity. However, they seem to be
      less suitable for monitoring specific responses to therapies and for predicting
      extra-articular manifestations as well as disease activity. Recent research
      activities center around using ACPA to further elucidate the pathogenesis of RA.

PMID- 19578862
TI  - Quadriceps force in relation of intrinsic anteroposterior stability of TKA
      design.
AB  - PURPOSE: Decreased quadriceps strength and fatigue is suspected to be one of the
      contributing factors for anterior knee pain and malfunction after total knee
      arthroplasty (TKA). The purpose of this in vitro study was to investigate the
      amount of quadriceps force required to extend the knee isokinetically after TKA
      in dependence of different prosthesis designs and the state of the posterior
      cruciate ligament (PCL). MATERIALS AND METHODS: Eight fresh frozen human knee
      specimens underwent testing in a kinematic device simulating an isokinetic knee
      extension cycle from 120 degrees  of flexion to full extension. The quadriceps
      force was measured after implantation of a cruciate retaining (CR) TKA (Genesis
      II, Smith&Nephew, Memphis, TN, USA) applying a conventional CR (11 mm) and a
      highly conforming (deep dished, DD) polyethylene (PE) inlay consecutively before
      and after resection of the PCL. Finally, tests were repeated with a posterior
      stabilized (PS) design. RESULTS: Simulating a physiological knee extension, no
      significant differences in the average quadriceps force were detected between the
      cruciate preserving inlays (CR 1,146.57 +/- 88.04 N, DD 1,150.19 +/- 97.54 N, P =
      0.86) as long as the PCL was intact. After resection of the PCL, the required
      quadriceps force increased significantly for both designs (CR 1,203.17 +/- 91.51
      N, P < 0.01 and DD 1,191.88 +/- 80.07 N, P < 0.03). After implantation of the
      posterior stabilized femoral component quad force decreased to its initial levels
      with forces significantly lower compared to the PCL deficient knees provided with
      a CR or DD (PS 1,130.91 +/- 107.88 N, P < 0.01) inlay. With a deficient PCL there
      were no statistical differences for the DD design in comparison with CR in mean
      quad forces (CR 1,203.17 +/- 91.51 N vs. DD 1,191.88 +/- 80.07 N, P = 0.50) nor
      in peak forces (CR 1,729.44 +/- 161.86 N, DD 1,688.66 +/- 123.18 N, P = 0.17).
      DISCUSSION: At intact PCL peak quad forces and mean forces beyond 70 degrees  of
      flexion could be shown to be significantly lower with a PS TKA design in
      comparison with cruciate preserving designs such as CR and DD. In the PCL
      deficient knee quad forces with a highly conforming implant (DD) and CR were
      significantly higher than with a PS TKA. The use of PS implants in all PCL
      deficient knees seems to be advisable

PMID- 19578863
TI  - Patellofemoral pressure after TKA in vitro: highly conforming vs. posterior
      stabilized inlays.
AB  - INTRODUCTION: When highly conforming polyethylene inlays were introduced into
      total knee arthroplasty (TKA), they were characterized as adding anteroposterior
      stability to the reconstructed knee. The aim of this study was to examine the
      patellofemoral pressure with the designs of a highly conforming and a posterior
      stabilized inlay. The patellofemoral pressure depends among other factors on the
      anteroposterior stability of the knee joint. MATERIALS AND METHODS: Eight fresh
      frozen human knee specimens underwent testing in a kinematic device. Knee motion
      was driven by a hydraulic cylinder at an extension moment of 31 Nm. The
      patellofemoral contact pressure was measured using a pressure sensitive film
      (Tekscan((R)), Inc., Boston, USA). First, this was assessed after implantation of
      a cruciate retaining (CR) TKA with a highly conforming polyethylene insert before
      and after resection of the posterior cruciate ligament. After that, the same
      measurements were performed with a similar posterior stabilized prosthesis.
      RESULTS: Patellofemoral contact pressures in the CR prosthesis using the highly
      conforming inlay were not significantly different before and after resection of
      the posterior cruciate ligament. However, after implantation of a posterior
      stabilized prosthesis peak pressure was significantly lower [Mean: 6.12, (SD
      2.37) MPa] in comparison to the highly conforming type [7.12, (SD 2.53) MPa, P <
      0.01] at a preserved posterior cruciate ligament. Further to that, the mean
      contact pressure turned out to be lower with the posterior stabilized design (P <
      0.006). CONCLUSION: The results of this study suggest that a posterior stabilized
      prosthesis design reduces the patellofemoral peak and mean pressure in comparison
      with a high conforming design. The better reproducible femoral rollback with a
      posterior stabilized model at a tibial ventral shift could serve as a possible
      explanation.

PMID- 19578864
TI  - Effect of erythromycin A and its new derivative EM201 on type I collagen
      production by cultured dermal fibroblasts.
AB  - Thinning of the dermis is the principal histological change in atrophic skin
      disorders and aged skin. It is caused due to a decreased amount of collagen in
      the dermis. Macrolides have been reported to exert various pharmacological
      activities, including anti-inflammatory activity, tumor angiogenesis inhibition
      and growth inhibition of fibroblasts, in addition to antimicrobial activity. In
      this study, we investigated the effects of erythromycin A (EMA) and its new
      derivative EM201 on type I collagen production by cultured dermal fibroblasts.
      Dermal fibroblasts were cultured with 10(-9) M-10(-5) M EMA or EM201, and
      collagen production was measured by incubation with radioactive proline, SDS
      polyacrylamide gel electrophoresis and fluorography. mRNA levels were measured by
      Northern blots analysis, and to investigate transcriptional levels luciferase
      assays were also performed. The results showed that both EMA and EM201 increased
      collagen production and type I collagen mRNA level (to a maximum of 200% with EMA
      and 250% with EM201) in a dose-dependent manner in cultured dermal fibroblasts.
      Transcription of the type I collagen gene was also increased by both macrolides.
      These results suggest that EMA and EM201 have the potential to improve the
      thinning of the dermis in atrophic skin disorders and aged skin.

PMID- 19578866
TI  - Diffusion-weighted magnetic resonance imaging in the management of cholesteatoma.
AB  - Diffusion-weighted (DW) MRI has recently increasingly gained popularity in the
      diagnosis of post-operative cholesteatoma. The aim of this study is to
      prospectively evaluate the usefulness of echo-planar imaging (EPI) for the
      diagnosis of residual cholesteatoma. Fifty patients underwent DW-EPI before
      surgery. Fifteen patients had a scan before their first surgery and 35 patients
      underwent neuroimaging prior to their second look surgery. In the first
      preoperative group of 15 patients, DW-EPI confirmed cholesteatoma in all the
      patients. In the post-operative group DW-EPI identified or excluded cholesteatoma
      correctly in 29 out of 35 patients. Our study has demonstrated a sensitivity of
      83% and specificity of 82% of DW-EPI for the diagnosis of residual cholesteatoma.
      DW-EPI can be a value imaging modality and may help the surgeon in selecting
      patients for revision surgery.

PMID- 19578865
TI  - Toll like receptor agonists augment HPV 11 E7-specific T cell responses by
      modulating monocyte-derived dendritic cells.
AB  - Impaired local cellular immunity is one of the mechanisms responsible for
      condyloma acuminatum (CA) recurrence. The activation of dendritic cells (DCs) is
      important in vaccine development. We investigated the effect of different toll
      like receptor (TLR) agonists including LPS (TLR4 agonist), polyinosinic acid
      polycytidylic acid (PIC, TLR3 agonist), CpG oligonucleotide (TLR9 agonist), and
      imiquimod (TLR7 agonist) on human monocyte-derived dendritic cells (mdDCs)
      loading of human papillomavirus (HPV) type 11 E7 epitope. As a result, we found
      that mdDCs loading HLA-A*0201-restricted HPV 11 E7 CTL epitope peptide could
      respond to the TLR agonists, especially LPS and PIC. This was characterized by an
      enhanced expression of CD40, CD80, CD86, CD83 and HLA-DR, and a high level of IL
      12 production. TLR agonists, especially PIC, enhanced the ability of E7-loaded
      mdDCs to induce IFN-gamma-secretion CD4(+) naive T cells. Moreover, E7-loaded
      mdDCs exposed to TLR agonists augmented autologous T cell responses including
      effector cytokines production and specific cytotoxic T lymphocyte (CTL)
      responses. In addition, the inhibitory effect of IL-10 on mdDCs maturation could
      be partially restored by LPS, PIC or imiquimod. Taken together, these results
      demonstrate that TLR agonists promoted the maturation of E7-loaded mdDCs and
      their ability to induce T help type 1 polarization and augment E7-specific T cell
      responses. These data also indicated that TLR3/4 agonists might be effective
      adjuvants of mdDC-based vaccines against CA.

PMID- 19578867
TI  - Zeste can facilitate long-range enhancer-promoter communication and insulator
      bypass in Drosophila melanogaster.
AB  - The looping model of enhancer-promoter interactions predicts that these specific
      long-range interactions are supported by a certain class of proteins. In
      particular, the Drosophila transcription factor Zeste was hypothesized to
      facilitate long-distance associations between enhancers and promoters. We have re
      examined the role of Zeste in supporting long-range interactions between an
      enhancer and a promoter using the white gene as a model system. The results show
      that Zeste binds to the upstream white promoter region and the enhancer that is
      responsible for white activation in the eyes. We have confirmed the previous
      finding that Zeste is not required for the activity of the eye enhancer and the
      promoter when they are located in close proximity to each other. However,
      inactivation of Zeste markedly affects the enhancer-promoter communication in
      transgenes when the eye enhancer and the white promoter are separated by a 3-kb
      spacer or the yellow gene. Zeste is also required for insulator bypass by the eye
      enhancer. Taken together, these results show that Zeste can support specific long
      range interactions between enhancers and promoters.

PMID- 19578868
TI  - Impact of fibronectin on surface properties of intraocular lenses.
AB  - PURPOSE: Physical properties of intraocular lens (IOL) surfaces determine
      biocompatibility. IOL hydrophobicity of commercially available IOLs with and
      without fibronectin (FN) coating can be determined by surface contact angle (SCA)
      measurements. SCA data of IOLs may allow for a rational selection of an IOL type
      as a function of underlying eye disease. SETTING: University Hospital of
      Saarland, Homburg (Saar), Germany METHODS: Thirteen IOL types were tested. IOLs
      were made of poly(methyl methacrylate)(PMMA), acrylate, or silicone. Select IOLs
      were surface modified by the manufacturer with heparin or a polysaccharide
      coating. SCA values of IOLs, either uncoated or precoated with FN, were
      determined using the sessile water drop method. RESULTS: SCA values ranged from
      61.3 to 116.1 degrees for unmodified IOLs, with PMMA IOLs being more hydrophilic
      (median SCA, 74.1 degrees ), silicone IOLs more hydrophobic (median SCA, 113.3
      degrees ), and acrylate IOLs intermediate (median SCA, 86.6 degrees ). Upon FN
      coating, all genuine acrylate lenses became significantly more hydrophilic while
      this effect was either nonsignificant or opposite on some PMMA and silicon IOLs.
      Heparin or polysaccharide surface modification resulted in significantly reduced
      SCA values. On acrylate IOLs, SCA values did not correlate with the aqueous
      content of the material. CONCLUSIONS: This study associates IOL materials,
      surface modifications, and the role of FN preadsorption with SCA values
      reflecting surface hydrophobicity versus hydrophilicity. It provides a rationale
      for specific IOL selection as a function of the clinical setting, and a basis for
      IOL development using tailored surface physicochemistry to enhance
      biocompatibility and to reduce susceptibility to implant infection.

PMID- 19578870
TI  - Assessment of cerebral oxygenation during prolonged simulated driving using near
      infrared spectroscopy: its implications for fatigue development.
AB  - Information on cerebral oxygenation during prolonged driving in healthy humans
      may help to explain the cause and development of central fatigue and its effects
      on cortex activities. The objective of this study is to investigate the time
      course of cerebral oxygenation during a prolonged driving task. Forty healthy
      male subjects were randomly divided into two groups: task group (Task) and
      control group (CNL). All subjects were required to rest well prior to the
      experiment. For the task group, subjects were required to perform the simulated
      driving task for 3 h. Cerebral oxygenation signal was monitored from the left
      frontal lobe using near infrared spectroscopy throughout the entire experiment.
      Significant increases in the concentrations of HbO(2) (DeltaCHbO(2)) and HbT
      (DeltaCHbT) were recorded at the start of driving task compared with the resting
      value (p < 0.01). The cerebral oxygen saturation in the Task group was found to
      be significantly lower following three hours of driving compared with that in the
      CNL (F = 16.95, p < 0.001). In addition, a significant difference in selective
      reaction time was observed between the Task group and CNL during the post-task
      period (p = 0.023). The results demonstrated that the cerebral oxygenation is
      closely related to the mental stress. The decrease in the cerebral oxygen
      saturation may indicate reduced cerebral oxygen delivery, and this may be an
      important factor affecting central fatigue development during prolonged driving.

PMID- 19578869
TI  - Microtubule-dependent formation of the stigmoid body as a cytoplasmic inclusion
      distinct from pathological aggresomes.
AB  - The stigmoid body (STB) is a neurocytoplasmic inclusion containing huntingtin
      associated protein 1 (HAP1), an interactor of huntingtin, and its formation is
      induced by transfection of HAP1-cDNA into cultured cells. Although STB is
      believed to play a protective role in polyglutamine diseases, including
      Huntington's disease and spinal and bulbar muscular atrophy, by sequestering the
      causative proteins, huntingtin and androgen receptor, respectively, its
      physiological function and formation remain poorly understood. Therefore, STB is
      occasionally confused with another cytoplasmic inclusion observed in
      polyglutamine diseases, the aggresome. Here we examined the subcellular dynamics
      of STB and compared it immunohistochemically and cytochemically with the
      aggresome in the rat brain and COS-7 or HeLa cells transfected with HAP1 and/or
      polyglutamine disease-associated genes. In time-lapse image analysis of HAP1
      transfected cells, the HAP1-induced STB is formed from multiple fusions of small
      HAP1 inclusions characterized by vigorous cytoplasmic movement. In HAP1
      transfected cells treated with a microtubule-depolymerizing drug, although the
      formation of small HAP1 inclusions was not affected, their fusion was critically
      inhibited. Immunohistochemistry and cytochemistry revealed the absence of
      association between STB and aggresomal markers, such as ubiquitin/proteasome,
      intermediate filaments, and the centrosome. Taken together, we concluded that STB
      is formed by a two-step process comprising microtubule-independent formation of
      small HAP1 inclusions and microtubule-dependent fusion of these inclusions, and
      that STB is distinct from pathological aggresomes.

PMID- 19578871
TI  - Preoperative 99Tc(m)-sestamibi scintigraphy with SPECT localizes most pathologic
      parathyroid glands.
AB  - BACKGROUND AND AIMS: Surgery is the only curative treatment for primary
      hyperparathyroidism. Focused surgical techniques are being practiced with
      increasing frequency. Preoperative imaging, such as scintigraphy, is a
      prerequisite for focused surgery. There is controversy about which preoperative
      imaging method should be used. The sensitivity reported for parathyroid
      scintigraphy varies considerably. This study was designed to determine the
      accuracy of the preoperative imaging routinely used at our institution. MATERIAL
      AND METHODS: This retrospective study included consecutive patients who underwent
      a routine dual-phase sestamibi-SPECT (single photon emission computed tomography)
      scintigraphy and subsequent operation with follow-up. Scintigraphy results were
      evaluated by comparing the results to surgical findings and histopathology.
      RESULTS: Two hundred and sixty-four individuals entered the study. Sensitivity
      for scintigraphy was 84%, specificity 91%, positive predictive value 91%, and
      negative predictive value 84%. CONCLUSIONS: Sestamibi-SPECT scintigraphy is a
      sensitive preoperative modality with high positive predictive value. Scintigraphy
      is a good indicator for when to perform a focused surgical approach and could
      often correctly guide the actual operation.

PMID- 19578872
TI  - Photorespiratory 2-phosphoglycolate metabolism and photoreduction of O2 cooperate
      in high-light acclimation of Synechocystis sp. strain PCC 6803.
AB  - In cyanobacteria, photorespiratory 2-phosphoglycolate (2PG) metabolism is
      mediated by three different routes, including one route involving the glycine
      decarboxylase complex (Gcv). It has been suggested that, in addition to
      conversion of 2PG into non-toxic intermediates, this pathway is important for
      acclimation to high-light. The photoreduction of O(2) (Mehler reaction), which is
      mediated by two flavoproteins Flv1 and Flv3 in cyanobacteria, dissipates excess
      reductants under high-light by the four electron-reduction of oxygen to water.
      Single and double mutants defective in these processes were constructed to
      investigate the relation between photorespiratory 2PG-metabolism and the
      photoreduction of O(2) in the cyanobacterium Synechocystis sp. PCC 6803. The
      single mutants Deltaflv1, Deltaflv3, and DeltagcvT, as well as the double mutant
      Deltaflv1/DeltagcvT, were completely segregated but not the double mutant
      Deltaflv3/DeltagcvT, suggesting that the T-protein subunit of the Gcv (GcvT) and
      Flv3 proteins cooperate in an essential process. This assumption is supported by
      the following results: (1) The mutant Deltaflv3/DeltagcvT showed a considerable
      longer lag phase and sometimes bleached after shifts from slow (low light, air
      CO(2)) to rapid (standard light, 5% CO(2)) growing conditions. (2)
      Photoinhibition experiments indicated a decreased ability of the mutant
      Deltaflv3/DeltagcvT to cope with high-light. (3) Fluorescence measurements showed
      that the photosynthetic electron chain is reduced in this mutant. Our data
      suggest that the photorespiratory 2PG-metabolism and the photoreduction of O(2),
      particularly that catalyzed by Flv3, cooperate during acclimation to high-light
      stress in cyanobacteria.

PMID- 19578874
TI  - Febrile seizures: a cloudy issue.

PMID- 19578873
TI  - Evaluation of the toxicity of stress-related aldehydes to photosynthesis in
      chloroplasts.
AB  - Aldehydes produced under various environmental stresses can cause cellular injury
      in plants, but their toxicology in photosynthesis has been scarcely investigated.
      We here evaluated their effects on photosynthetic reactions in chloroplasts
      isolated from Spinacia oleracea L. leaves. Aldehydes that are known to stem from
      lipid peroxides inactivated the CO(2) photoreduction to various extents, while
      their corresponding alcohols and carboxylic acids did not affect photosynthesis.
      alpha,beta-Unsaturated aldehydes (2-alkenals) showed greater inactivation than
      the saturated aliphatic aldehydes. The oxygenated short aldehydes
      malondialdehyde, methylglyoxal, glycolaldehyde and glyceraldehyde showed only
      weak toxicity to photosynthesis. Among tested 2-alkenals, 2-propenal (acrolein)
      was the most toxic, and then followed 4-hydroxy-(E)-2-nonenal and (E)-2-hexenal.
      While the CO(2)-photoreduction was inactivated, envelope intactness and
      photosynthetic electron transport activity (H(2)O --> ferredoxin) were only
      slightly affected. In the acrolein-treated chloroplasts, the Calvin cycle enzymes
      phosphoribulokinase, glyceraldehyde-3-phosphate dehydrogenase, fructose-1,6
      bisphophatase, sedoheptulose-1,7-bisphosphatase, aldolase, and Rubisco were
      irreversibly inactivated. Acrolein treatment caused a rapid drop of the
      glutathione pool, prior to the inactivation of photosynthesis. GSH exogenously
      added to chloroplasts suppressed the acrolein-induced inactivation of
      photosynthesis, but ascorbic acid did not show such a protective effect. Thus,
      lipid peroxide-derived 2-alkenals can inhibit photosynthesis by depleting GSH in
      chloroplasts and then inactivating multiple enzymes in the Calvin cycle.

PMID- 19578875
TI  - Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of
      5-aza-2'-deoxycytidine against synovial sarcoma cell lines.
AB  - PURPOSE: In this study, the methylation status of RASSF1A in synovial sarcomas
      and the effect of demethylation on synovial sarcoma were examined. METHODS: The
      methylation status in 74 soft tissue sarcomas (STSs) including 21 synovial
      sarcomas was determined by methylation specific PCR. The effect of the de
      methylating agent 5-aza-20-deoxycytidine (5-Aza-dC) on synovial sarcoma was
      examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II). RESULTS: RASSF1A
      methylation was observed in 10 (47.6%) of 21 synovial sarcomas and in 10 (18.9%)
      of 53 the other STSs (P = 0.0295). De-methylation of the cells by treatment with
      5-Aza-dC induced re-expression of RASSF1A and growth suppression of the cells.
      The calculated IC50 of 5-Aza-dC against the SYO-1 and the HS-SYII cells were 0.9
      and 1.3 lM (96 h), respectively. With twice weekly administration of 1 or 10
      mg/kg 5-Aza-dC, the growth of the mouse xenograft tumors of SYO-1 was
      significantly suppressed in comparison to the controls (P?0.01). CONCLUSION: This
      is the first report showing the anti-tumor effect of 5-Aza-dC on synovial
      sarcoma. 5-Aza-dC is suggested to have a good therapeutic potential against
      synovial sarcoma.

PMID- 19578877
TI  - Hydrophobic modification of sodium alginate and its application in drug
      controlled release.
AB  - Sodium alginate was hydrophobically modified by coupling of polybutyl
      methacrylate onto the alginate. The polybutyl methacrylate was previously
      prepared through polymerization of butyl methacrylate in the presence of 2-amino
      ethanethiol as a chain transfer agent. The structure of the product was
      characterized by Fourier-transformed infrared spectrometry, nuclear magnetic
      resonance ((1)HNMR) and thermogravimetry. The result of fluorescence analysis
      showed that the hydrophobicity of the modified alginate was obviously increased.
      The modified alginate conjugate was used for immobilization of bovine serum
      albumin in the presence of calcium chloride. In addition, the release behavior of
      the drug-loaded alginate in deionized water and Tris-HCl buffer solution (pH 7.2)
      was investigated. It was found that the modified sodium alginate possessed
      prolonged release behavior compared to unmodified sodium alginate, and it had
      potential application in controlled release as a drug carrier.

PMID- 19578876
TI  - The ERAP2 gene is associated with preeclampsia in Australian and Norwegian
      populations.
AB  - Preeclampsia is a heritable pregnancy disorder that presents new onset
      hypertension and proteinuria. We have previously reported genetic linkage to
      preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ)
      familial cohort. This current study centered on identifying the susceptibility
      gene(s) at the 5q locus. We first prioritized candidate genes using a
      bioinformatic tool designed for this purpose. We then selected a panel of known
      SNPs within ten prioritized genes and genotyped them in an extended set of the
      Aust/NZ families and in a very large, independent Norwegian case/control cohort
      (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a
      genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene
      (rs3734016, P (uncorr) = 0.009) and for the endoplasmic reticulum aminopeptidase
      2 (ERAP2) gene (rs2549782, P (uncorr) = 0.004). In the Norwegian cohort we
      identified evidence of a genetic association for ERAP1 (rs34750, P (uncorr) =
      0.011) and for ERAP2 (rs17408150, P (uncorr) = 0.009). The ERAP2 SNPs in both
      cohorts remained statistically significant (rs2549782, P (corr) = 0.018;
      rs17408150, P (corr) = 0.039) after corrections at an experiment-wide level. The
      ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood
      pressure regulation and essential hypertension in addition to innate immune and
      inflammatory responses. Perturbations within vascular, immunological and
      inflammatory pathways constitute important physiological mechanisms in
      preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus,
      ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder.

PMID- 19578878
TI  - Kinetic and redox properties of MnP II, a major manganese peroxidase isoenzyme
      from Panus tigrinus CBS 577.79.
AB  - A manganese peroxidase (MnP) isoenzyme from Panus tigrinus CBS 577.79 was
      produced in a benchtop stirred-tank reactor and purified to apparent homogeneity.
      The purification scheme involving ultrafiltration, affinity chromatography on
      concanavalin-A Sepharose, and gel filtration led to a purified MnP, termed "MnP
      II," with a specific activity of 288 IU mg(-1) protein and a final yield of 22%.
      The enzyme turned out to be a monomeric protein with molecular mass of 50.5 kDa,
      pI of 4.07, and an extent of N-glycosylation of about 5.3% of the high-mannose
      type. The temperature and pH optima for the formation of malonate manganic
      chelates were 45 degrees C and 5.5, respectively. MnP II proved to be poorly
      thermostable at 50 and 60 degrees C, with half-lives of 11 min and 105 s,
      respectively. K (m) values for H(2)O(2) and Mn(2+) were 16 and 124 microM,
      respectively. Although MnP II was able to oxidize veratryl alcohol and to
      catalyze the Mn(2+)-independent oxidation of several phenols, it cannot be
      assigned to the versatile peroxidase family. As opposed to versatile peroxidase
      oxidation, veratryl alcohol oxidation required the simultaneous presence of
      H(2)O(2) and Mn(2+); in addition, low turnover numbers and K (m) values higher
      than 300 microM characterized the Mn(2+)-independent oxidation of substituted
      phenols. Kinetic properties and the substrate specificity of the enzyme markedly
      differed from those reported for MnP isoenzymes produced by the reference strain
      P. tigrinus 8/18. To our knowledge, this study reports for the first time a
      thorough electrochemical characterization of a MnP from this fungus.

PMID- 19578879
TI  - Abstracts of the 14th International Conference on Biological Inorganic Chemistry.
      July 25-30, 2009. Nagoya, Japan.

PMID- 19578912
TI  - Contact mechanics and rubber friction for randomly rough surfaces with
      anisotropic statistical properties.
AB  - In this paper we extend the theory of contact mechanics and rubber friction
      developed by one of us (B.N.J. Persson, J. Chem. Phys. 115, 3840 (2001)) to the
      case of surfaces with anisotropic surface roughness. As an application we
      calculate the viscoelastic contribution to the rubber friction. We show that the
      friction coefficient may depend significantly on the sliding direction, while the
      area of contact depends weakly on the sliding direction. We have carried out
      experiments for rubber blocks sliding on unidirectionally polished steel
      surfaces. The experimental data are in a good qualitative agreement with the
      theory.

PMID- 19578911
TI  - Members of the Dof transcription factor family in Triticum aestivum are
      associated with light-mediated gene regulation.
AB  - DNA binding with One Finger (Dof) protein is a plant-specific transcription
      factor implicated in the regulation of many important plant-specific processes,
      including photosynthesis and carbohydrate metabolism. This study has identified
      31 Dof genes (TaDof) in bread wheat through extensive analysis of current
      nucleotide databases. Phylogenetic analysis suggests that the TaDof family can be
      divided into four clades. Expression analysis of the TaDof family across all
      major organs using quantitative RT-PCR and searches of the wheat genome array
      database revealed that the majority of TaDof members were predominately expressed
      in vegetative organs. A large number of TaDof members were down-regulated by
      drought and/or were responsive to the light and dark cycle. Further expression
      analysis revealed that light up-regulated TaDof members were highly correlated in
      expression with a number of genes that are involved in photosynthesis or sucrose
      transport. These data suggest that the TaDof family may have an important role in
      light-mediated gene regulation, including involvement in the photosynthetic
      process.

PMID- 19578913
TI  - The UV-vis absorption spectrum of the flavonol quercetin in methanolic solution:
      A theoretical investigation.
AB  - The UV-vis absorption spectrum of the solvated quercetin molecule in methanol was
      investigated theoretically by means of an elegant type of QM/MM scheme better
      known as sequential Monte Carlo/quantum mechanics (S-MC/QM) methodology. A set of
      125 uncorrelated Monte Carlo molecular liquid structures were properly selected
      through the autocorrelation function of the energy in order to be used in the
      quantum mechanical calculations. These molecular liquid structures were obtained
      by means of the radial and minimum distance distribution functions. A detailed
      account of the pattern of hydrogen bond structures obtained in this study is also
      available. The computed results obtained here were directly compared with the
      available experimental data in order to validate our theoretical model and
      through this comparison a very good conformity between theoretical and available
      experimental results was found.

PMID- 19578914
TI  - Evaluating patient-specific abdominal aortic aneurysm wall stress based on flow
      induced loading.
AB  - In this paper, we develop a physiologic wall stress analysis procedure by
      incorporating experimentally measured, non-uniform pressure loading in a patient
      based finite element simulation. First, the distribution of wall pressure is
      measured in a patient-based lumen cast at a series of physiologically relevant
      steady flow rates. Then, using published equi-biaxial stress-deformation data
      from aneurysmal tissue samples, a nonlinear hyperelastic constitutive equation is
      used to describe the mechanical behavior of the aneurysm wall. The model accounts
      of the characteristic exponential stiffening due to the rapid engagement of
      nearly inextensible collagen fibers and assumes, as a first approximation, an
      isotropic behavior of the arterial wall. The results show a complex wall stress
      distribution with a localized maximum principal stress value of 660 kPa on the
      inner surface of the posterior surface of the aneurysm bulge, a considerably
      larger value than has generally been reported in calculations of wall stress
      under the assumption of uniform loading. This is potentially significant since
      the posterior wall has been suggested as a common site of rupture, and the
      aneurysmal tensile strength reported by other authors is of the same order of
      magnitude as the maximum stress value found here.

PMID- 19578916
TI  - Regression analysis for peak designation in pulsatile pressure signals.
AB  - Following recent studies, the automatic analysis of intracranial pressure (ICP)
      pulses appears to be a promising tool for forecasting critical intracranial and
      cerebrovascular pathophysiological variations during the management of many
      disorders. A pulse analysis framework has been recently developed to
      automatically extract morphological features of ICP pulses. The algorithm is able
      to enhance the quality of ICP signals, to segment ICP pulses, and to designate
      the locations of the three ICP sub-peaks in a pulse. This paper extends this
      algorithm by utilizing machine learning techniques to replace Gaussian priors
      used in the peak designation process with more versatile regression models. The
      experimental evaluations are conducted on a database of ICP signals built from
      700 h of recordings from 64 neurosurgical patients. A comparative analysis of
      different state-of-the-art regression analysis methods is conducted and the best
      approach is then compared to the original pulse analysis algorithm. The results
      demonstrate a significant improvement in terms of accuracy in favor of our
      regression-based recognition framework. It reaches an average peak designation
      accuracy of 99% using a kernel spectral regression against 93% for the original
      algorithm.

PMID- 19578915
TI  - Influence of selecting EPI readout-encoding bandwidths on arterial spin labeling
      perfusion MRI.
AB  - OBJECT: The objective of this study was to investigate effects of varying readout
      bandwidths on the arterial spin labeling (ASL)-perfusion MRI measurements at a
      high magnetic field MRI system. MATERIALS AND METHODS: Brain perfusion studies
      were performed on nine volunteers (four males, five females) using flow sensitive
      alternating inversion recovery (FAIR) ASL single-shot echo-planar imaging (EPI)
      MRI. To investigate EPI bandwidth effects on the time-series perfusion-weighted
      imaging (PWI) data, two regions-of-interest (ROI) were placed outside the brain
      to determine the level of noise and another ROI inside the brain to determine the
      level of signal. Coefficients of variations (CoV) were calculated for the time
      series PWI data. One-way analysis of variance (ANOVA) was used to investigate
      voxel-wise differences in the time-series PWI data between two different
      bandwidth values. RESULTS: At the level of ROI, there was no significant effect
      of changing EPI bandwidths on the time-series PWI data in any of the volunteers
      (P > 0.031). In contrast, CoV values over the dynamic PWI data varied with
      depending on selecting EPI bandwidths and voxel-based tests showed that N2
      ghosting, modulated by EPI bandwidth, can appear in some brain regions,
      especially in areas that overlap with the spatial distribution of N2 ghosting
      artifacts. CONCLUSIONS: Although N2 ghosting can be reduced by adjusting the
      bandwidth of EPI on the time-series of PWI data, the effects cannot be entirely
      eliminated. In particular, N2 ghosting can bias CBF quantification if EPI control
      scans to determine the equilibrium-state signal are confounded by N2 ghosting.
      Therefore, careful tuning of the bandwidth of EPI is necessary to avoid artifacts
      in the ASL signal from N2-ghosting.

PMID- 19578917
TI  - Association of ER-alpha gene polymorphism with metabolic phenotypes in Chinese
      Hans.
AB  - Recently, two polymorphisms (rs1884052 and rs3778099) of estrogen receptor alpha
      (ER-alpha) gene were identified as being associated with primary quantitative
      bone mineral density (BMD) in a genome-wide association (GWA) study in Framingham
      cohorts. In this study we aimed at investigating the association of rs1884052 and
      rs3778099, and another polymorphism (rs2234693) located at intron 1 of the ER
      alpha gene with BMD, body mass index (BMI), glucose, triglyceride, and total
      cholesterol (CHO) levels in Chinese Hans. We recruited 425 consecutive adult
      volunteers who had a physical examination in the Jinan Maternity and Child Care
      Hospital. We did not observe significant association of rs1884052 and rs3778099
      with BMD, BMI, glucose, triglyceride, and total cholesterol (CHO) levels. For
      rs2234693, increased levels of BMD for hip, spine or whole-body regions were
      consistently observed in TT/TC genotype carriers than in CC genotype carriers,
      although the board line significance diminished after adjusting for age and
      gender. However, significant association of rs2234693 with glucose and CHO levels
      were observed in our sample. Subjects with TC/CC genotypes were associated with
      an increased level of glucose (p = 0.013) and CHO (p = 0.032) levels than
      subjects with TT genotypes. In conclusion, we did not confirm the association of
      rs1884052 and rs3778099 with BMD originally discovered in a GWA study; however,
      we made novel discoveries that rs2234693 was associated with glucose and CHO
      levels in Chinese Hans.

PMID- 19578922
TI  - Hydatid disease of right ventricle and pulmonary arteries: a rare cause of
      pulmonary embolism--computed tomography and magnetic resonance imaging findings
      (2009: 5b).
AB  - Hydatid disease can occur anywhere in the body and can demonstrate different
      imaging features that vary according to growth stage, associated complications,
      and affected tissue. Cardiovascular system involvement of hydatid disease is very
      rare. In this article, we present the cardiac magnetic resonance (MR) and thorax
      computed tomography (CT), MR angiography (MRA) findings of hydatid cysts located
      in the right ventricle and pulmonary arteries after surgical removal of hepatic
      hydatid cysts.

PMID- 19578924
TI  - The Val/Met functional polymorphism in COMT confers susceptibility to bipolar
      disorder: evidence from an association study and a meta-analysis.
AB  - The COMT gene is considered as one of the prominent candidate genes for
      susceptibility to BP, and most studies focused a functional polymorphism in the
      gene: the Val/Met polymorphism (rs4680). However, results from these studies are
      sometimes contradictory, due to small sample size or heterogeneity. In this
      study, we first investigate the possible association between the Val/Met
      polymorphism in COMT and bipolar disorder in the Han population, which has never
      been done before. Then a systematic meta-analysis was conducted to determine if
      the low-activity allele (Met) increases the risk of BP in different ethnic
      groups. A total of 478 BP patients and 469 healthy subjects were recruited in our
      case/control study. MIX software package was employed to perform the meta
      analysis on 19 studies after careful search and selection. We observed
      statistically-significant differences in allele (p = 0.00060) and genotype (p =
      0.00203) frequencies between patients and controls in our samples. The meta
      analysis also provided a significant pooled OR for association of the Met allele
      in rs4680 with BP in the total population (p = 0.0223) and in the Asian
      population (p = 0.0232). Although a significant pooled OR was also found for the
      Caucasian population (p = 0.0409) after one of the studies as discussed below was
      removed, the role for Val/Met polymorphism in BP in Caucasian ethnicity was not
      yet to be confirmed. In conclusion, the low-activity allele (Met) of rs4680 in
      COMT gene possibly confers risk for bipolar disorder in the Han population, while
      it needs further evidence for concluding its association with BP in the Caucasian
      population.

PMID- 19578926
TI  - The complete nucleotide sequence of an isolate of Asian prunus virus 1 from peach
      [Prunus persica (L) Batch].

PMID- 19578927
TI  - Characterization of anti-idiotypic antibodies mimicking antibody- and receptor
      binding sites on hepatitis A virus.
AB  - Two anti-idiotypic monoclonal antibodies (mAb2s; named 94-2 and 94-7), were
      generated from a BALB/c mouse immunized with human monoclonal anti-hepatitis A
      virus (HAV) neutralizing antibody KF94. We characterized the properties of the
      mAb2s and determined interactions between mAb2s, KF94 and HAV using enzyme-linked
      immunosorbent assay, immunofluorescence assay and HAV infectivity assay.
      Inactivated HAV inhibited mAb2 binding to KF94, indicating that the mAb2s
      mimicked the HAV neutralization site that was complementary to the paratope of
      KF94. MAb2 94-7 competed with an anti-HAV cellular receptor antibody for binding
      to HAV-susceptible cells and partially blocked virus infection. We speculated
      that mAb2 94-7 mimicked a portion of the HAV receptor-binding site. The ability
      to generate mAb2 implies that HAV receptor-binding sites are exposed on the
      surface of HAV, permitting antibody access.

PMID- 19578928
TI  - Genetic analysis of avian influenza A viruses isolated from domestic waterfowl in
      live-bird markets of Hanoi, Vietnam, preceding fatal H5N1 human infections in
      2004.
AB  - The first known cases of human infection with highly pathogenic avian influenza
      (HPAI) H5N1 viruses in Vietnam occurred in late 2003. However, HPAI H5N1 and low
      pathogenic avian influenza (LPAI) H5N2 and H9N3 viruses were isolated from
      domestic waterfowl during live-bird market (LBM) surveillance in Vietnam in 2001
      and 2003. To understand the possible role of these early viruses in the genesis
      of H5N1 strains infecting people, we performed sequencing and molecular
      characterization. Phylogenetic analysis revealed that the hemagglutinin (HA)
      genes of two geese HPAI H5N1 strains belonged to clade 3, and their surface
      glycoprotein and replication complex genes were most closely related (98.5-99.7%
      homologous) to A/duck/Guangxi/22/01 (H5N1) virus, detected contemporarily in
      southern China, whilst the M and NS genes were derived from an A/duck/Hong
      Kong/2986.1/00 (H5N1)-like virus. The H5 HA gene of the duck HPAI H5N1 strain
      belonged to clade 5 and acquired a gene constellation from
      A/quail/Shantou/3846/02 (H5N1), A/teal/China/2978.1/02 (H5N1) and
      A/partridge/Shantou/2286/03 (H5N1)-like viruses. The phylogenetic analysis
      further indicated that all eight gene segments of goose and duck HPAI H5N1 and
      LPAI H5N2 viruses were distinct from those of H5N1 clade-1 viruses known to have
      caused fatal human infections in Vietnam since late 2003. The duck H9N3 isolates
      derived genes from aquatic-bird influenza viruses, and their H9 HA belonged to
      the Korean lineage. The PB2 gene of A/duck/Vietnam/340/01 (H9N3) virus had lysine
      at position 627. Based on the molecular characterization of specific amino acid
      residues in the surface and relevant internal protein-coding genes, the
      Vietnamese H5N1 and H9N3 virus isolates indicated specificity to avian cell
      surface receptor and susceptibility for currently licensed anti-influenza A virus
      chemotherapeutics. Our findings suggest that the H5N1 and H5N2 viruses that
      circulated among geese and ducks in LBMs in Hanoi, Vietnam, during 2001 and 2003
      were not the immediate ancestors of the clade-1 viruses associated with fatal
      human infections in Vietnam. The clade-1 HPAI H5N1 viruses were independently
      introduced into Vietnam.

PMID- 19578929
TI  - Selection of a cold-adapted bacterium for bioremediation of wastewater at low
      temperatures.
AB  - Amongst more than 1000 isolates collected in various cold environments, the
      strain Arthrobacter psychrolactophilus Sp 31.3 has been selected for its ability
      to grow and to produce exoenzymes at low temperatures, its inability to grow at
      37 degrees C, its non-halophilic character and its growth versatility on various
      media. This non-pathogenic strain displays a strong resistance to desiccation and
      storage at room temperature and is suitable for the production of freeze-dried
      bacterial starters. When grown in a synthetic wastewater at 10 degrees C, the
      strain induces a complete clarification of the turbid medium and efficiently
      hydrolyses proteins, starch and lipids in the broth. Furthermore, this strain has
      a remarkable capacity to improve the biodegradability of organic compounds in
      wastewater as indicated by a BOD(5)/COD ratio of 0.7.

PMID- 19578925
TI  - Molecular mechanisms underlying synergistic effects of SSRI-antipsychotic
      augmentation in treatment of negative symptoms in schizophrenia.
AB  - Negative symptoms in schizophrenia respond poorly to antipsychotics, but may
      improve when these are augmented with selective serotonin reuptake inhibitors
      (SSRIs). The molecular mechanisms underlying the augmentation are unclear.
      Nevertheless, significant progress has been made, pointing to some candidate
      systems which may be involved in SSRI-antipsychotic synergism. Thus, the enhanced
      dopamine release by SSRI-antipsychotic treatment is modulated by specific
      serotonergic receptors and by tyrosine hydroxylase. There are modifications in
      gamma-aminobutyric acid system via glutamate decarboxylase 67, protein kinase C
      beta and the receptor for activated C-kinase 1 (Rack1). Some studies indicate the
      input of transcription and neurotrophic factors as phospho-cyclic adenosine
      monophosphate response element-binding protein, Fos and fibroblast growth factor
      2. Alterations in calcium signaling (neurogranin, regulator of G-protein
      signaling and Rack1) and in cytokine receptors for interleukin-8 and chemokine
      have also been reported. While as yet limited in scope, the evidence suggests
      definable molecular targets which may be implicated in drug development based on
      SSRI-antipsychotic synergistic actions.

PMID- 19578931
TI  - QT dispersion and transmural dispersion of repolarization in patients with
      familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is a disease characterized by sporadic,
      paroxysmal attacks of fever and serosal inflammation. QT dispersion (QTd) and
      transmural dispersion of repolarization (TDR), simple noninvasive arrhythmogenic
      markers, that can be used to assess homogeneity of cardiac repolarization, have
      not been studied in FMF patients before. The aim of our study was to evaluate the
      QTd and TDR in FMF patients without overt cardiac involvement. A total of 50
      patients with FMF (30 men, 20 women, 29.4 +/- 11.8 years) and 50 controls (30
      men, 20 women; mean age 31.3 +/- 11.9 years) were included. QTd, corrected QTd
      (cQTd), maximum QT (QTmax), maximum corrected QT (cQTmax), minimum QT (QTmin),
      and minimum corrected QT intervals (cQTmin) and TDR were measured from standard
      12-lead electrocardiography (ECG). We found that QTd, QTmax, and TDR were greater
      in FMF patients than in the control group (36.0 +/- 11.4 vs. 20 +/- 11.2, P <
      0.001 and 354.8 +/- 30.9 vs. 342.8 +/- 18.0, P = 0.02; 62.0 +/- 16.0 vs. 49.0 +/-
      9.5 P < 0.001, respectively), as were cQTd and cQTmax (40.4 +/- 13.5 vs. 21.9 +/-
      12.4, P < 0.001 and 397.7 +/- 40.2 vs. 375.5 +/- 25.4 P = 0.001). A modest
      positive correlation was found between cQTd and C-reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR) (r = 0.30, P < 0.001; r = 0.40, P < 0.001;
      respectively). QTd, which is an index of inhomogeneity of ventricular
      repolarization and an important predictor of cardiovascular mortality, and TDR,
      which is a better marker of cardiac repolarization, increased in FMF patients
      similarly as in other rheumatologic diseases.

PMID- 19578930
TI  - How long is strict bed rest necessary after renal biopsy?
AB  - BACKGROUND: No consensus exists on the amount of bed rest required after renal
      biopsy. Moreover, forced prolonged bed rest can be uncomfortable in patients
      undergoing renal biopsy. OBJECTIVE: To evaluate whether the length of strict bed
      rest affects the incidence of pain and other complications after renal biopsy.
      STUDY DESIGN, FACILITY, AND PATIENTS: This single-center retrospective
      observational study was conducted in 94 consecutive patients undergoing biopsy of
      a native kidney between November 2005 and December 2006 at Mie University
      Hospital. The control group was composed of 317 patients who underwent biopsy of
      a native kidney between January 2001 and October 2005. METHODS: The incidence of
      biopsy-related complications was compared between two periods of strict bed rest:
      2 h of strict bed rest with no abdominal bandage (November 2005 to December 2006)
      and 7 h of strict bed rest with an abdominal bandage (January 2001 to October
      2005). The primary outcome was the incidence of back pain requiring analgesics.
      The secondary outcomes were: need for transfusion or hemostatic intervention,
      decrease of >/=10% in hemoglobin (Hb) after biopsy, macroscopic hematuria,
      infection possibly related to biopsy, need for single or indwelling bladder
      catheterization, and other biopsy-related complications. RESULTS: The incidence
      of back pain requiring analgesics decreased with a shorter period of strict bed
      rest [7.5% versus 21.1%, odds ratio (OR) 0.30, 95% confidence interval (95% CI)
      0.12-0.64, p = 0.004]. Even after adjustment for age, sex, perinephric hematoma
      size, and number of biopsy punctures, the incidence of back pain decreased
      significantly (OR 0.34, 95% CI 0.14-0.73, p = 0.01). With a shorter period of
      strict bed rest, there were no significant differences in bleeding complications
      (need for transfusion or other hemostatic intervention), decrease of >or=10% in
      Hb or macroscopic hematuria. However, the need for indwelling bladder
      catheterization decreased significantly (36.2% versus 50.5%, OR 0.55, 95% CI 0.34
      0.88, p = 0.013). CONCLUSIONS: Shortening the period of strict bed rest after
      renal biopsy from 7 h to 2 h decreased the incidence of back pain, but there was
      no increase in bleeding or other biopsy-related complications. Our findings
      suggest that a shorter period of strict bed rest can safely reduce discomfort in
      renal biopsy patients.

PMID- 19578932
TI  - Prediction of DAS28-ESR remission at 6 months by baseline variables in patients
      with rheumatoid arthritis treated with etanercept in Japanese population.
AB  - We tried to determine which baseline variables are responsible for remission
      induction at 6 months in unselected rheumatoid arthritis (RA) patients of
      Japanese population treated with etanercept. One hundred forty-one patients with
      RA who were administered etanercept were registered. Thirty-four patients were
      started on etanercept monotherapy, 60 patients on cotherapy with methotrexate
      (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX
      nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy).
      None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at
      entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR
      remission at 6 months. We examined association of gender, DAS at baseline, MTX
      cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at
      baseline with achievement of remission at 6 months by logistic regression
      analysis. All subjects were classified as having high (N = 109) or moderate
      disease activity (N = 32) at entry. One hundred twenty out of 141 patients
      (85.1%) continued treatment with etanercept at 6 months. Continuation rate was
      statistically higher in MTX cotherapy (93.3%) compared with etanercept
      monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%).
      Logistic regression analysis identified that MTX cotherapy at entry and moderate
      disease activity at entry were independent variables for remission induction at 6
      months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX
      cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a
      lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with
      etanercept monotherapy. In this study of unselected patients, use of MTX and
      moderate disease activity at entry were associated with higher likelihood of
      response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA
      patients administrated etanercept who are intolerant to MTX.

PMID- 19578934
TI  - Abundant conserved microRNA target sites in the 5'-untranslated region and coding
      sequence.
AB  - Recent studies have shown that miRNAs can target the promoter and CDS region.
      Thus, we predicted miRNA target sites in the 5'-UTR, CDS and 3'-UTR of Homo
      sapiens, Mus musculus and Drosophila melanogaster using miRanda and TargetScan.
      Target-site densities normalized with the average region length were higher in
      the 5'-UTR than 3'-UTR in all three organisms but were lower in the negative data
      set. Interestingly, the putative target sites were more conserved than non-target
      regions in both the 5'-UTR and 3'-UTR, implying that target sites in the 5'-UTR
      are subject to high selective pressure and might be functional. In Drosophila, 48
      of 78 (61.5%) miRNAs showed high similarities with predicted siRNAs. Based on the
      results of previous experimental studies and a large-scale statistical analysis,
      we conclude that miRNA-mediated regulation is not limited to the 3'-UTR. However,
      the functionality of target sites in the 5'-UTR and CDS requires thorough
      investigation.

PMID- 19578935
TI  - Lay interpersonal sources for health information related to beliefs about the
      modifiability of cancer risk.
AB  - OBJECTIVE: Causal beliefs about cancer may influence preventive behaviors and
      medical care. We examined the relationship between beliefs about causation for
      lung, colon, and skin cancer and the use of lay interpersonal sources of health
      information (community organizations, family, friends). METHODS: Data from a
      nationally representative sample of 5,119 adult respondents to the 2005 Health
      Information National Trends Survey were analyzed. RESULTS: About 40% of
      respondents reported that community organizations provided them with health
      information, while 15% discussed health information "very frequently" with their
      family or friends. In multivariate models, individuals who never spoke with
      family or friends about health were more likely to believe that colon cancer risk
      is not modifiable; those provided with health information by community
      organizations were less likely to believe that skin cancer risk is not
      modifiable. Speaking with family or friends about health was also associated with
      endorsing the belief that skin cancer is caused by behavior or lifestyle.
      CONCLUSION: These findings showed that lay interpersonal health information
      sources are associated with beliefs about the modifiability of colon and skin
      cancer risk. Future research is needed to investigate whether and how such
      information sources might influence decisions about engaging in preventive
      behaviors.

PMID- 19578937
TI  - Identification and developmental expression of Dec2 in zebrafish.
AB  - The involvement of Dec2, a member of the basic helix-loop-helix (bHLH) family, in
      cellular differentiation, hypoxia response, and circadian regulation has been
      investigated. Here we report the previously unknown spatiotemporal expression of
      Dec2 in zebrafish embryogenesis. Dec2 is dynamically expressed in zebrafish
      pineal gland, tract of the postoptic commissure, brain, notochord, heart, common
      cardinal vein (CCV), axial vein, pronephric duct, swim bladder, and early somites
      during embryogenesis, which implies that Dec2 is involved in zebrafish central
      nervous system development, cardiogenesis, and internal organs and somites
      formation. The embryonic expression patterns of zebrafish Dec2 and its homolog
      Dec1 partially overlap, but are distinct from each other. The Dec2 expression
      level was lower than that of Dec1 during zebrafish embryogenesis. Although Dec1
      also contributed to zebrafish somites formation, cardiogenesis, and internal
      organs and central nervous system development, the two Dec genes were not likely
      to be simply redundant during zebrafish embryogenesis. Our results imply that
      Dec2, like its homolog Dec1, is involved in zebrafish cardiogenesis, central
      nervous system development, and internal organs and somites formation with
      distinct developmental roles.

PMID- 19578936
TI  - Dairy intake and 1,25-dihydroxyvitamin D levels in men at high risk for prostate
      cancer.
AB  - OBJECTIVE: Dairy food intake has been associated with prostate cancer in previous
      work, but the mechanism by which this occurs is unknown. Dairy calcium may
      suppress circulating levels of potentially cancer-protective 1,25-hydroxyvitamin
      D (1,25(OH)2D). We examined the associations of dairy, milk, calcium, and vitamin
      D intake with plasma 1,25(OH)2D levels among 296 men (194 black, 102 non-black)
      enrolled in a high risk program for prostate cancer from 10/96 to 10/07. METHODS:
      All participants completed diet and health history questionnaires and provided
      plasma samples, which were assessed for levels of 25-hydroxyvitamin D and
      1,25(OH)2D. We used multivariate linear regression to examine associations with
      1,25(OH)2D. RESULTS: After adjustment for age, race, energy intake, BMI, and
      alcohol intake, we observed no associations for any of our variables of interest
      with 1,25(OH)2D, or any meaningful differences in estimates by race or vitamin D
      status. CONCLUSION: Our findings, in a sample including a large proportion of
      black participants, do not confirm previous findings showing an inverse
      association between calcium intake and 1,25(OH)2D levels. As such, they suggest
      that future work should explore other mechanisms by which dairy foods and calcium
      might increase prostate cancer risk.

PMID- 19578938
TI  - Pectoral fins of Micropogonias furnieri: a histochemical and ultrastructural
      study.
AB  - The myotomal fibres of the pectoral fins of white croaker (Micropogonias
      furnieri) have been studied using histochemical techniques and transmission
      electron microscopy (TEM). Succinic dehydrogenase (SDH) for mitochondria,
      periodic acid Schiff (PAS) for glycogen, Sudan Black for lipids and myosin
      adenosintriphosphatase (mATPase) pre-incubated at alkaline and acid pHs were used
      to visualize the contraction velocity. Three zones were determined: superficial
      (SZ), medium (MZ) and deep (DZ). Staining for SDH, PAS and Sudan Black was
      positive only in the SZ. The level of alkaline mATPase was the highest in fibres
      from the DZ, intermediate in the MZ and low in the SZ; at an acid pH, the reverse
      was obtained. Fibres from the SZ were small with large quantities of
      subsarcolemmal mitochondria, scarce intermyofibrilar mitochondria and a well
      developed sarcoplasmic reticulum; the myofibrils displayed a polygonal
      distribution along the entire length of the fibre. Fibres in the MZ were larger
      than those in the SZ, the myofibrils were densely packed, mitochondria prevailed
      under the sarcolemma and the sarcoplasmic reticulum was not abundant. Fibres from
      the DZ were the largest, with ribbon-shaped myofibrils and scarce mitochondria.
      The intercellular space was abundant and nervous endings were frequently
      observed.

PMID- 19578939
TI  - Expression pattern of prmt5 in adult fish and embryos of medaka, Oryzias latipes.
AB  - DNA methylation is an important biochemical epigenetic determinant of gene
      expression in cells and therefore actively involved in gene regulation,
      chromosomal conformation, and protein activity. Protein arginine
      methyltransferases (PRMTs) play a major role in the methylation of proteins that
      have an arginine residue, catalyzing both the asymmetric dimethylation of
      arginine (aDMA) and symmetric dimethylation of arginine (sDMA). PRMT5, a type II
      PRMT which catalyzes sDMA, has been shown to have a pivotal role in pole plasm
      assembly and germ cell development in Drosophila and also to be an associate
      factor of Blimp1 for germ cell development in mouse. Here, we report a homolog of
      prmt5 identified in medaka, Oryzias latipes, which was detected in the brain,
      gill, muscle, heart, liver, spleen, intestine, testis and ovary of adult fish by
      reverse transcriptase-PCR. The expression of prmt5 in the gonads is restricted to
      oocytes of the ovary, spermatogonia, and spermatocytes of testis. The prmt5
      transcripts were detected as early as the one-cell stage and in all the tissues
      of embryos during embryogenesis. In summary, prmt5 is a maternal determinant
      factor of embryogenesis of medaka, possibly playing an important role in
      oogenesis and spermatogenesis in adult medaka.

PMID- 19578940
TI  - Polymorphisms within promoter of Japanese flounder (Paralichthys olivaceus) ovary
      cytochrome P450-c19 (CYP19a) gene associated with reproductive traits.
AB  - Cytochrome P450 aromatase, which is encoded by the CYP19a gene, converts
      androgens to estradiol. Considerable evidence suggests that estrogens play an
      important role in fish reproductive process. Therefore CYP19a is an excellent
      candidate gene for reproductive traits. Variants in the promoter of the CYP19a
      gene might also be involved in the control of aromatase expression and affect
      regulatory mechanism linking cholesterol metabolism to the synthesis of sex
      steroids. In this study, nine single-nucleotide polymorphisms (SNPs) were
      detected with polymerase chain reaction-single stranded conformational
      polymorphism (PCR-SSCP), namely A-680G, G-672A, AGTAGT-649 inserting or deleting,
      T-623C, C-410A, T7-454A, T-402C, TTTCCAGACTGA-345 inserting or deleting, and G
      297C. Nine SNPs within the promoter of the CYP19a gene were tested for
      association with four reproductive traits [serum testosterone (T), serum 17beta
      estradiol (E(2)), hepatosomatic index (HSI), and gonadosomatic index (GSI)] in a
      population of 50 female Japanese flounder individuals. A locus, P3 (TTTCCAGACTGA
      345 inserting or deleting, G-297C), was significantly associated with 17beta
      estradiol (E(2)) level (P < 0.05) in female Japanese flounder. In addition, there
      was significant association between one diplotype based on nine SNPs and
      reproductive trait. The genetic effect for E(2) level of diplotype D3 was
      significantly higher than those of other diplotypes (P < 0.05). Results indicate
      that these genetic effects of those variants on E(2) level may help to explain
      CYP19a gene status in the reproductive endocrinology of Japanese flounder.

PMID- 19578941
TI  - Application of molecular topology to the prediction of mosquito repellents of a
      group of terpenoid compounds.
AB  - A topological-mathematical model based on multilinear regression analysis has
      been built to search new terpenoid actives as mosquito repellents. The structural
      depiction was performed using topological indices, and a four-variable model for
      the prediction of corrected repellent ratio (r (2) = 0.9672, Q (2) = 0.9435) was
      selected. The model was checked by cross-validation, internal validation, and
      randomization test. The results confirm its capability to predict the property
      analyzed. After carrying out a virtual screening upon such a model, new
      structures with potential repellent activity against mosquitoes are proposed.

PMID- 19578943
TI  - Diastereoselective synthesis of fused [1,3]oxazines from ethyl pyruvate,
      activated acetylenes and N-heterocycles.
AB  - The 1:1 zwitterionic intermediates obtained from the reaction between
      isoquinoline, quinoline, pyridine, or N-methylimidazole with activated acetylenes
      are trapped by ethyl pyruvate to produce highly functionalized fused
      [1,3]oxazines in good yields.

PMID- 19578944
TI  - Synthesis of new tripodal Hantzsch 1,4-dihydropyridines under solvent-free
      condition and their conversion to the corresponding tripodal pyridines.
AB  - A mixture of beta-ketoester and tri-aldehydes in the presence of ammonium
      fluoride was converted to their corresponding tripodal 1,4-dihydropyridines under
      solvent-free condition with good yields. The obtained tripodal 1,4
      dihydropyridines were also aromatized with oxone((r))/NaNO(2)/wet SiO(2) system
      under mild and heterogeneous conditions quantitatively.

PMID- 19578945
TI  - Diversity-oriented synthesis of benzimidazole, benzoxazole, benzothiazole and
      quinazolin-4(3H)-one libraries via potassium persulfate-CuSO4-mediated oxidative
      coupling reactions of aldehydes in aqueous micelles.
AB  - Libraries of 2-substituted-benzimidazoles, benzoxazoles, benzothiazoles as well
      as quinazolin-4(3H)-ones were synthesized via potassium persulfate-CuSO(4)
      mediated oxidative coupling of aldehydes with o-phenylenediamines, o
      aminophenols, o-aminothiophenols, and anthranilamide, respectively, in aqueous
      micelles. The strategy opens a way for rapid generation of libraries of small
      heterocycles for biological screening. The reagent is commercially available,
      cheap, and highly chemoselective. The yields were superior in aqueous micelles to
      those in organic solvents. Short reaction times, large-scale synthesis, excellent
      chemoselectivity, excellent yields, as well as environmental friendliness are the
      main advantages of this diversity-oriented synthesis.

PMID- 19578942
TI  - QSAR for RNases and theoretic-experimental study of molecular diversity on
      peptide mass fingerprints of a new Leishmania infantum protein.
AB  - The toxicity and low success of current treatments for Leishmaniosis determines
      the search of new peptide drugs and/or molecular targets in Leishmania pathogen
      species (L. infantum and L. major). For example, Ribonucleases (RNases) are
      enzymes relevant to several biologic processes; then, theoretical and
      experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs)
      of RNases is useful for drug design. This study introduces a methodology that
      combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy
      (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We
      illustrate this approach by investigating for the first time the PMFs of a new
      protein of L. infantum. Here we report and compare new versus old predictive
      models for RNases based on Topological Indices (TIs) of Markov Pseudo-Folding
      Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include:
      Spectral moments pi ( k )(x,y), Mean Electrostatic potentials xi ( k )(x,y), and
      Entropy measures theta ( k )(x,y). The accuracy of the models (training/cross
      validation) was as follows: xi ( k )(x,y)-model (96.0%/91.7%)>pi ( k )(x,y)-model
      (84.7/83.3) > theta ( k )(x,y)-model (66.0/66.7). We also carried out a 2D-E
      analysis of biological samples of L. infantum promastigotes focusing on a 2D-E
      gel spot of one unknown protein with M<20, 100 and pI <7. MASCOT search
      identified 20 proteins with Mowse score >30, but not one >52 (threshold value),
      the higher value of 42 was for a probable DNA-directed RNA polymerase. However,
      we determined experimentally the sequence of more than 140 peptides. We used QSAR
      models to predict RNase scores for these peptides and BLAST alignment to confirm
      some results. We also calculated 3D-folding TIs based on MD experiments and
      compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular
      diversity of these peptides. This combined strategy may be of interest in drug
      development or target identification.

PMID- 19578946
TI  - Evaluation of HSP70, 27 and TNF-alpha expression [corrected] in different canine
      cutaneous and gland diseases.

PMID- 19578947
TI  - Phenotypic expression of 2b myosin heavy chain isoform: a comparative study among
      species and different muscles.

PMID- 19578948
TI  - Analysis of a candidate gene for behavioural trait variability in horses:
      catechol-O-methyltransferase (COMT).

PMID- 19578949
TI  - Study on the application of an interspecific competition model for the prediction
      of microflora behaviour during the fermentation process of S. Angelo PGI salami.

PMID- 19578950
TI  - Evaluation of the shelf life of vacuum- and modified atmosphere packaged
      Dicentrarchus labrax fillets.

PMID- 19578951
TI  - Protein breakdown and volatile profile of low-acid sausages from crossbreed pigs.

PMID- 19578952
TI  - Monitoring of levels of polycyclic aromatic hydrocarbons in bees caught from
      beekeeping: remark 1.

PMID- 19578954
TI  - Assessment of a gel column technique for feline blood typing.

PMID- 19578953
TI  - Specificity and sensitivity of ultrasonography and endoscopy for the diagnosis of
      exercise-induced pulmonary haemorrhage (EIPH) in 157 race horses.

PMID- 19578955
TI  - Involvement of the kallikrein-kinin system in a model of hyperalgesia in low
      kallikrein rats.

PMID- 19578956
TI  - Use of magnetic resonance imaging in the diagnosis of bone marrow edema in the
      equine distal limb: six cases.

PMID- 19578957
TI  - Cellular immune response and immunotoxicity induced by DON (deoxynivalenol) in
      piglets.

PMID- 19578958
TI  - Cutaneous lymphomatoid granulomatosis (angiotropic lymphoma) in a dog:
      immunophenotyping analysis.

PMID- 19578959
TI  - Three-dimensional microvasculature remodeling study of pig periovulatory
      follicles using vascular corrosion casts.

PMID- 19578960
TI  - Dog assisted interventions in a specialized centre and potential concerns for
      animal welfare.

PMID- 19578961
TI  - In vivo study of the behaviour of matrix metalloproteinases (MMP-2, MMP-9) in
      mechanical, hypoxic and septic-induced acute lung injury.

PMID- 19578962
TI  - Functional identification of bovine mammary epithelial stem/progenitor cells.

PMID- 19578963
TI  - Expression of alpha-transducin, a chemoreceptive molecule, in endocrine and non
      endocrine cells of the pig gastrointestinal tract.

PMID- 19578964
TI  - Stanniocalcin 1 is a potential physiological modulator of steroidogenesis in the
      swine ovarian follicle.

PMID- 19578965
TI  - Plant derived veterinary vaccines.
AB  - Infectious diseases remain one of the main causes of death and economic losses in
      animals despite the fact that prophylactic vaccination has been extremely
      successful in disease prevention. New effective viral, bacterial and parasitic
      vaccines are needed, but unfortunately production costs still remain prohibitive.
      In this respect plants can offer a valid alternative. Production of antigenic
      proteins in plants relies on a well developed and proven technology, several
      expression platforms are available and many different plant species can be
      utilized. Plant based veterinary vaccine studies have addressed protection issues
      in model animals and, more interestingly, some of them have examined the relevant
      challenge model in the specific species of interest. A general overview of the
      topic will be outlined together with a few selected promising examples.

PMID- 19578966
TI  - Echinococcus multilocularis in Europe--state of the art.
AB  - New information has become available on the epidemiological situation of
      Echinococcus multilocularis in Europe. Additional endemic areas have been
      identified, and, in some areas, prevalences in foxes have drastically increased.
      In addition, some neozootic mammals may by now be involved in the lifecycle. The
      parasite is now widespread in urban and suburban areas in central Europe. The
      number of human cases of alveolar echinococcosis is small, but still
      underreported, and is likely to increase in the near future. Trials to counteract
      the spread of this parasite have been performed by application of anthelmintics
      to foxes via baits, and gave encouraging results on different spatial scales.

PMID- 19578967
TI  - Chemical-nutritional characteristics of diets in aquaculture.
AB  - After a brief discussion on the chemical-nutritional characteristics of the diets
      currently used in aquaculture, the authors focus attention on the problems
      associated with the replacement of fish meals with vegetable protein sources. The
      chemical composition of vegetable sources has a high variability and it is
      necessary to know the exact energy content and digestibility of amino-acids for
      each source. Another question is the occurrence of anti-nutritional factors in
      vegetable protein sources and their effect on diet palatability. The authors also
      underline that the use of high levels of vegetable sources increases the risk of
      contamination by mycotoxins of which the effects on the health of fish are not
      yet completely clear. Finally, brief considerations are reported on the
      relationship between the chemical-nutritional characteristics of diets and that
      of the resulting fish fillets.

PMID- 19578968
TI  - Natural history of CKD stage 4 and 5 patients following referral to renal
      management clinic.
AB  - BACKGROUND: CKD patients referred to a renal management clinic are looked after
      by a multidisciplinary team whose care may improve outcome and delay the
      progression of kidney disease. This paper describes our experience and the
      results obtained in 940 patients with CKD stage 4 and 5 patients from two renal
      management clinics (RMC). SUBJECTS AND METHODS: We collected and analyzed the
      data from 940 patients with CKD stage 4 and 5 at the RMCs of the Toronto General
      Hospital (TGH), University Health Network and The Scarborough General Hospital
      (TSH) from January 2000 to November 2007. Inclusion criteria for the study
      required at least three measurements of serum creatinine over a minimum follow-up
      of 6 months. We calculated the change of slope of the estimated GFR by linear
      regression analysis. The slopes were further subdivided into five groups:
      improved eGFR (eGFR slope >or=+5 ml/min/year); mild improvement (slope >+1 to <+5
      ml/min/year); stable (slope <+1 to >-1 ml/min/year); slow progression (i.e.,
      deterioration; slope <-1 to >-5 ml/min/year) and rapid progression (slope >-5
      ml/min/year). RESULTS: During a median follow-up of 1.57 year (range 0.5-8.7
      year) of stage 4 patients, eGFR improved in 10.6%, showed mild improvement in
      24.2%, was stable in 27.5%, showed slow progression in 28.8% and rapid
      progression in 8.9% of patients. During a median follow-up of 1.4 year (range 0.5
      8 year) of CKD stage 5 patients, eGFR improved in only 1.3%, showed mild
      improvement in 4.3%, remained stable in 35.6%; showed slow progression in 19.7%
      and rapid progression in 39.1%. Between the two hospitals (TGH and TSH) there was
      a statistically significant difference in the number of visits per year for CKD
      stage 4 patients during the first, second and third year. However, the number of
      visits per year had no effect on the rate of decline. On univariate analysis,
      factors predicting non-progression in eGFR slope were eGFR at referral, the use
      of ACE inhibitors-ARBs and absence of cardiovascular disease. However, in
      logistic multivariate regression analysis, after adjusting for confounding
      factors only the eGFR at referral and ACE inhibitors-ARBs were independent
      factors for non-progression in eGFR. A significant percentage of CKD stage 4
      patients attending a renal management clinic (RMC) showed non-progression or
      improvement in their kidney function. Although only few stage 5 CKD patients had
      improvement in their eGFR, 32% of them maintained their eGFR on conservative
      treatment for over 2 years delaying the initiation of dialysis.

PMID- 19578969
TI  - Equilibration kinetics in isolated and membrane-bound photosynthetic reaction
      centers upon illumination: a method to determine the photoexcitation rate.
AB  - Kinetics of electron transfer, following variation of actinic light intensity,
      for photosynthetic reaction centers (RCs) of purple bacteria (isolated and
      membrane-bound) were analyzed by measuring absorbance changes in the primary
      photoelectron donor absorption band at 865 nm. The bleaching of the primary
      photoelectron donor absorption band in RCs, following a sudden increase of
      illumination from the dark to an actinic light intensity of I(exp), obeys a
      simple exponential law with the rate constant alphaI(exp) + k(rec), in which
      alpha is a parameter relating the light intensity, measured in mW/cm(2), to a
      corresponding theoretical rate in units of reciprocal seconds, and k(rec) is the
      effective rate constant of the charge recombination in the photosynthetic RCs. In
      this work, a method for determining the alpha parameter value is developed and
      experimentally verified for isolated and membrane-bound RCs, allowing for
      rigorous modeling of RC macromolecule dynamics under varied photoexcitation
      conditions. Such modeling is necessary for RCs due to alterations of the forward
      photoexcitation rates and relaxation rates caused by illumination history and
      intramolecular structural dynamics effects. It is demonstrated that the classical
      Bouguer-Lambert-Beer formalism can be applied for the samples with relatively low
      scattering, which is not necessarily the case with strongly scattering media or
      high light intensity excitation.

PMID- 19578971
TI  - A tribute to Achim Trebst, a friend.
AB  - I honor here a friend, Achim Trebst, on his 80th birthday on June 9, 2009. I have
      known his outstanding research, on the biochemistry of photosynthesis, for years.
      My brief tribute, which includes personal, scientific and a cultural component,
      is followed by excellent tributes by Volker ter Meulen and Rudolf K. Thauer, by
      Heinrich Strotmann, and by Walter Oettmeier (this issue).

PMID- 19578970
TI  - Ultrafast transient absorption spectroscopy: principles and application to
      photosynthetic systems.
AB  - The photophysical and photochemical reactions, after light absorption by a
      photosynthetic pigment-protein complex, are among the fastest events in biology,
      taking place on timescales ranging from tens of femtoseconds to a few
      nanoseconds. The advent of ultrafast laser systems that produce pulses with
      femtosecond duration opened up a new area of research and enabled investigation
      of these photophysical and photochemical reactions in real time. Here, we provide
      a basic description of the ultrafast transient absorption technique, the laser
      and wavelength-conversion equipment, the transient absorption setup, and the
      collection of transient absorption data. Recent applications of ultrafast
      transient absorption spectroscopy on systems with increasing degree of
      complexity, from biomimetic light-harvesting systems to natural light-harvesting
      antennas, are presented. In particular, we will discuss, in this educational
      review, how a molecular understanding of the light-harvesting and photoprotective
      functions of carotenoids in photosynthesis is accomplished through the
      application of ultrafast transient absorption spectroscopy.

PMID- 19578972
TI  - Celebrating Achim Trebst's 80th birthday.
AB  - At the invitation of Govindjee, we reprint here the English translation of the
      letter, in German, that we sent, on behalf of the Senate and the Presidium as
      well as the members of the German Academy of Sciences Leopoldina, from Halle
      (Saale), to Professor Dr. Dr. h.c.mult. Achim Trebst on his 80th birthday. The
      original of this letter written in German will appear in Jahrbuch 2009, Deutsche
      Akademie der Naturforscher Leopoldina, Halle (Saale), Wissenschaftliche
      Verlagsgesellschaft mbH Stuttgart.

PMID- 19578973
TI  - A tribute to Achim Trebst at the time of his doctor honoris causa, University of
      Dusseldorf.
AB  - On June 9, 2009, we celebrate the 80th birthday of Achim Trebst. I present below
      the "Tribute" (Laudatio) that I read on February 11, 2000 on the occasion of his
      receiving Doctor honoris causa of the Faculty of Mathematics and Natural Sciences
      of the Heinrich Heine University in Dusseldorf. The text below is a translation
      from the original German to English with minor editorial changes by Govindjee.

PMID- 19578974
TI  - Achim Trebst, my senior, and our joint research.
AB  - In this tribute, I offer my best wishes to Achim Trebst on his 80th birthday on
      June 9, 2009. At the invitation of Govindjee, I present here a perspective of
      some of our joint research during 1970s through 2000s.

PMID- 19578975
TI  - Molecular cloning and characterization of five genes encoding pentatricopeptide
      repeat proteins from Upland cotton (Gossypium hirsutum L.).
AB  - The pentatricopeptide repeat (PPR) protein family is one of the largest and most
      complex families in plants. These proteins contain multiple 35-amino acid repeats
      that are proposed to form a super helix capable of binding RNA. PPR proteins have
      been implicated in many crucial functions broadly involving organelle biogenesis
      and plant development. In this study, we identified many genes encoding PPR
      protein in Upland cotton through an extensive survey of the database of Gossypium
      hirsutum. Furthermore, we isolated five full-length cDNA of PPR genes from G.
      hirsutum 0-613-2R which were named GhPPR1-GhPPR5. Domain analysis revealed that
      the deduced amino acid sequences of GhPPR1-5 contained from 5 to 10 PPR motifs
      and those PPR proteins were divided into two different PPR subfamilies. GhPPR1-2
      belonged to the PLS subfamily and GhPPR3-5 belonged to the P subfamily.
      Phylogenetic analysis of the five GhPPR proteins and 18 other plant PPR proteins
      also revealed that the same subfamily clustered together. All five GhPPR genes
      were differentially but constitutively expressed in roots, stems, leaves,
      pollens, and fibers based on the gene expression analysis by real-time
      quantitative RT-PCR. This study is the first report and analysis of genes
      encoding PPR proteins in cotton.

PMID- 19578976
TI  - Efficient isolation of high quality nucleic acids from different tissues of Taxus
      baccata L.
AB  - Improved and efficient methods were developed for isolating high quality DNA and
      RNA from different sources of Iranian Yew (Taxus baccata L.). The methods were
      based on CTAB extraction buffer added with high levels of polyvinylpyrrolidone
      (PVP) and beta-mercaptoethanol to properly remove polysaccharides and prevent
      oxidation of phenolics. The pellets obtained by ethanol precipitation were washed
      only with Chloroform: isoamyl alcohol (24:1). So, we could successfully eliminate
      the dangerous phenol/chloroform extraction steps from the isolation procedure.
      Both spectrophotometric (A(260)/A(280) and A(260)/A(230) ratios) and agarose
      electrophoresis analysis of isolated nucleic acids (DNA and RNA) indicated good
      results. DNA with the average yield of 100-300 microg/g leaf and stem tissue and
      total RNA with an average yield of 20-30 microg/g cell culture and 80-100
      microg/g leaf and stem tissue of Iranian yew could be obtained. Successful
      amplification of pam and pds by PCR and RT-PCR, showed the integrity of isolated
      DNA and RNA, respectively.

PMID- 19578977
TI  - Identification and expression analysis of two zebrafish E2F5 genes during
      oogenesis and development.
AB  - During the process of screening genes that are preferentially expressed in
      zebrafish germ cells, we isolated an E2F family member zE2F5b, which is a
      truncated isoform of zebrafish E2F5a. The E2F transcription factors are thought
      to play an essential role in cell cycle progression. Reverse transcription
      polymerase chain reaction and whole mount in situ hybridization analyses have
      demonstrated that both zE2F5a and zE2F5b mRNAs are predominantly expressed in
      stage I and II oocytes. In early development, the two zE2F5 transcripts are
      expressed by many parts of the embryo and are then restricted to the brain area.
      Interestingly, zE2F5b mRNA is detected later in the lens and optic tectum while
      zE2F5a mRNA is absent. Our data suggests that E2F5 may play important roles in
      zebrafish brain, eye and ovarian development.

PMID- 19578978
TI  - The mitochondrial genome of Euphausia superba (Prydz Bay) (Crustacea:
      Malacostraca: Euphausiacea) reveals a novel gene arrangement and potential
      molecular markers.
AB  - Euphausiid krill are dominant organisms in the zooplankton population and play a
      central role in marine ecosystems. In this paper, we described the gene
      organization, gene rearrangement and codon usage in the mitochondrial genome of
      Euphausia superba Dana 1852 (sampling from Prydz Bay, PB). The mitochondrial
      genome of E. superba is more than 15,498 bp in length (partial non-coding region
      was not determined). Translocation of four tRNAs (trnL ( 1 ), trnL ( 2 ), trnW
      and trnI) and duplication of one tRNA (trnN) were founded in the mitochondrial
      genome of E. superba when comparing its genome with the pancrustacean ground
      pattern. To investigate the phylogenetic relationship within Malacostraca,
      phylogenetic trees based on currently available malacostracan mitochondrial
      genomes were built with the maximum likelihood and the Bayesian models. All
      analyses based on nucleotide and amino acid data strongly support the monophyly
      of Stomatopoda, Penaeidae, Caridea, and Brachyura, which is consistent with
      previous research. However, the taxonomic position of Euphausiacea within
      Malacostraca is unstable. From comparing the mitochondrial genome between E.
      superba (PB) and E. superba (sampling from Weddell Sea, WS), we found that nad2
      gene contains maximal variation with 61 segregating sites, following by nad5 gene
      which has 12 segregating sites. Thus, nad2 and nad5 genes may be used as
      potential molecular markers to study the inherit diversity among different E.
      superba groups, which would be helpful to the exploitation and management of E.
      superba resources.

PMID- 19578979
TI  - Mycophenolic acid inhibits albumin-induced MCP-1 expression in renal tubular
      epithelial cells through the p38 MAPK pathway.
AB  - Proteinuria is a well-established exacerbating factor in chronic kidney disease.
      Although the mechanisms of albumin-induced tubulointerstitial damage have been
      extensively studied, the influence of mycophenolic acid (MPA) on tubular
      epithelial cells has not been sufficiently elucidated. MPA, the active metabolite
      of mycophenolate mofetil, is a potent, non-competitive, and reversible inhibitor
      of inosine-5'-monophosphate dehydrogenase, the rate-limiting enzyme for de novo
      purine synthesis. Monocyte chemoattractant protein 1 (MCP-1) is a 76-amino-acid
      chemokine thought to be the major chemotactic factor for monocytes. MCP-1 is
      found in macrophage-rich areas of atherosclerotic lesions. However, the
      mechanisms regulating MCP-1 expression by MPA in renal tubular epithelial cells
      were still unclear. In this study, the inhibitory effect of MPA on MCP-1
      expression by albumin-induced renal tubular epithelial cells was investigated,
      and the roles of p38 mitogen-activated protein kinase (p38 MAPK) pathway were
      explored. MPA attenuated albumin-induced expression of MCP-1 mRNA and protein.
      The experiment suggested that MPA actively inhibited protein of MCP-1. The
      inhibitory effect of MPA on MCP-1 expression was mediated by the sequential
      attenuation of p38 MAPK expression. These inhibitory effects were partially
      inhibited by SB203580, a specific inhibitor of p38 MAPK. Taken together, these
      results suggest that the negative modulation of MCP-1 by MPA is partly dependent
      on p38 MAPK pathway.

PMID- 19578980
TI  - Serum level of soluble 70-kD heat shock protein is associated with high mortality
      in patients with colorectal cancer without distant metastasis.
AB  - Many findings indicate that measuring the serum concentration of soluble 70-kD
      heat shock protein (soluble HSP70) may provide important information in
      cardiovascular, inflammatory, and pregnancy-related diseases; however, only
      scarce data are available in cancer. Therefore, using a commercial ELISA kit, we
      measured soluble HSP70 concentration in the sera of 179 patients with colorectal
      cancer. We investigated the relationship between soluble HSP70 concentration and
      mortality, during 33.0 (24.4-44.0) months long follow-up. High (>1.65 pg/ml,
      median concentration) soluble HSP70 level was a significant (hazard ratio: 1.88
      (1.20-2.96, p = 0.005) predictor of mortality during the follow-up period. When
      we compared the soluble HSP70 levels in patients with non-resected primary tumors
      as compared to those who were recruited into the study 4-6 weeks after the tumor
      resection they were found to be significantly (p = 0.020) higher in the former
      group. Since the patients with non-resected primary tumors had also distant
      metastasis and died early, we limited the further analysis to 142 patients with
      no distant metastasis at the beginning of the follow-up. This association
      remained significant even after multiple Cox-regression analysis had been
      performed to adjust the data for age and sex (p = 0.028); age, sex, and TNM-T
      stage (p = 0.041); age, sex, and TNM-N stage (p = 0.021); age, sex, and
      histological grade (p = 0.023); or age, sex, and tumor localization (p = 0.029).
      Further analysis showed that the significant association between high HSP70
      levels and poor survival is in the strongest in the group of <70-year-old female
      patients (HR: 5.52 (2.02-15.15), p = 0.001), as well as in those who were in a
      less advanced stage of the disease at baseline. These novel findings indicate
      that the serum level of soluble HSP70 might prove a useful, stage-independent
      prognostic marker in colorectal cancer without distant metastasis.

PMID- 19578981
TI  - High expression of claudin-1 protein in papillary thyroid tumor and its regional
      lymph node metastasis.
AB  - Claudins, known as major contributors in the formation of the tight junction, are
      differentially expressed in malignant tumors as compared to the corresponding
      healthy tissues. Therefore, they are thought to play a role in carcinogenesis and
      tumor progression. Altered expression of claudin-1 has been reported in several
      tumor types including endometrial, papillary renal cell and colonic carcinoma,
      and increased claudin-1 mRNA levels have been observed in papillary thyroid
      carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1
      expression in various types of thyroid lesions at the protein level and
      investigating the immunolocalization of beta-catenin reported to regulate claudin
      1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph
      node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid
      carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by
      quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was
      detected in the majority of PTC/PMC primary tumors and lymph node metastases
      (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1
      expression in any of the FA and FTC cases or peritumoral non-malignant thyroid
      tissues. Our data prove that high claudin-1 protein expression is specific for
      PTC and its regional lymph node metastases, while we failed to verify that
      claudin-1 is regulated by beta-catenin in thyroid tumors. Based on these results,
      claudin-1 may be a useful tumor marker for PTC.

PMID- 19578982
TI  - A new strategy for assembling multifunctional nanocomposites with iron oxide and
      amino-terminated PAMAM dendrimers.
AB  - A new strategy for assembling multifunctional nanocomposites with magnetic
      particles and amino dendrimers was reported. In this strategy, the amino
      terminated PAMAM G5.0 and Fe(3)O(4) NPs prepared by co-deposition method and
      further modified by aminosilane by two sol-gel processes were combined with the
      hydrophilic spacer of PEG dicarboxylate by amidation. The nanocomposites were
      characterized by means of X-ray diffraction (XRD), transmission electron
      microscopy (TEM), X-ray photoelectron spectroscopy (XPS), atom force microscopy
      (AFM), superconducting quantum interference device (SQUID) magnetometer, and
      hydrophilicity analysis. The results showed that the multifunctional
      nanocomposites were spherical with the mean diameter of 180 nm and exhibited good
      dispersion and hydrophilicity. The new strategy put forward here provides an
      effective route to functionalizing Fe(3)O(4) NPs with various amino dendrimers
      for drug and gene delivery as well as biological detection.

PMID- 19578983
TI  - Is video-game playing a risk factor for pathological gambling in Australian
      adolescents?
AB  - Very little research has been conducted to examine the relationship between video
      game playing and gambling in adolescence. In this study, 2,669 adolescents aged
      13-17 years were surveyed to obtained details of their involvement in gambling
      and video-game playing as well as a measure of pathological gambling (the DSM-IV
      J). The results showed that, the frequency of video game playing was
      significantly related to pathological gambling, but that the effect size was very
      small and largely accounted for by the greater popularity of both activities
      amongst boys. There was some evidence for stronger associations between
      technologically similar activities, namely arcade video games and an interest in
      gaming machines, but other factors discussed in the paper may also account for
      this association. In summary, the findings suggested that playing video-games is
      unlikely to be a significant risk factor for pathological gambling during
      adolescence.

PMID- 19578984
TI  - The influence of substance dependence and mood disorders on outcome from
      pathological gambling: five-year follow-up.
AB  - A prospective study of the role of comorbid substance abuse and dependence and
      mood disorders in the outcome from pathological gambling. A naturalistic sample
      of pathological gamblers who had recently quit gambling (N = 101) was followed
      and data were available for 83% of participants at 3 months, 80% at 12 months,
      and 52% at 5 years. Those participants with a drug diagnosis during their
      lifetime were less likely to have a minimum 3 month period of abstinence, and
      those who had been involved in gambling treatment were more likely to have a
      minimum 12 months of continuous abstinence. Lifetime gambling problem severity
      and involvement in gambling treatment were most commonly associated with a
      shorter time to achieving a period of abstinence of any length. Lifetime history
      of a mood disorder also predicted a longer time to reach a minimum 3 months of
      continuous abstinence. Both gambling treatment and an alcohol diagnosis follow up
      predicted an increase in the odds of experiencing a relapse from a minimum 6
      month period of abstinence. Overall, comorbid mental health disorders are
      predictive of shorter term but not longer term outcome.

PMID- 19578985
TI  - Target-mediated drug disposition model: relationships with indirect response
      models and application to population PK-PD analysis.
AB  - The paper focuses on approximations of the target-mediated drug disposition
      (TMDD) model as applied to pharmacodynamic (target kinetics) modeling. The TMDD
      equation for the total target concentration is shown to coincide with the
      indirect response model with stimulation or inhibition of elimination. This
      correspondence allows estimation of pharmacodynamic TMDD parameters and
      unobservable free target concentrations using indirect-response models. The
      ability of the TMDD model and its approximations to estimate the unobservable
      free target concentration is investigated by simulation. Pharmacokinetic
      parameters used for simulations were parameters typical for monoclonal
      antibodies. TMDD binding and target turnover parameters were similar to those
      estimated for omalizumab. Free drug and total target concentrations were
      measured. The simulated population PK-PD study demonstrated that for drugs with
      TMDD, indirect-response models are in fact mechanistic models that can be used to
      estimate TMDD model parameters and unobservable free target concentrations that
      are important for pharmacodynamic modeling.

PMID- 19578986
TI  - Fluorescent biological label for recognizing human ovarian tumor cells based on
      fluorescent nanoparticles.
AB  - In this paper, we report a method for recognizing human ovarian tumor (HOT) cells
      using fluorescent biological label based on core-shell nanoparticles. The
      luminescent nanoparticles were synthesized with a water-in-oil (W/O)
      microemulsion technique. The fluorescent silica core-shell nanoparticles modified
      with anti-HER2 antibody using bifunctional cross-linker glutaraldehyde targeted
      the corresponding tumor antigen in the cell surface of the SKOV3 ovarian cancer
      cells. The specific immunoreactivity of antibody-nanoparticles with cells was
      characterized by laser scanning microscopy (LSM) and scanning electron microscope
      (SEM). The results showed that the method offered potential advantages of
      sensitivity and simplicity due to high binding efficiency between nanoparticles
      and cells and provided an alternative method for the detection of HOT.

PMID- 19578987
TI  - Synthesis, crystal structure, DNA-binding properties and cytotoxic activity of
      the copper (II) complex involving xanthone.
AB  - 1, 8-(3, 6, 9-Trioxaundecane-1, 11-diyldioxy)xanthone (L), and its new Cu (II)
      complex [Cu.L.(CH3CN)2](ClO4)2 have been synthesized and characterized by 1H NMR,
      electrospray mass spectra (ESI-MS), elemental analyses, infrared spectra (IR) and
      X-ray single crystal diffraction. The crystal structure of complex shows that Cu
      (II) ion is encapsulated within the macrocycle of L. The geometry around copper
      is a distorted square bipyramid with two acetonitrile molecules at axial
      position, and four macrocyclic oxygens including the carbonyl oxygen on the
      equatorial positions. The interaction of Cu (II) complex with calf thymus DNA (ct
      DNA) has been investigated by spectrophotometric titrations, ethidium bromide
      (EB) displacement experiments, circular dichroism (CD) spectra and viscosity
      measurements. Results indicate that Cu (II) complex can intercalate into the DNA
      base pairs by the plane of xanthone ring. Furthermore, the Cu (II) complex was
      tested against tumor cell lines including ECA109, SGC7901 and GLC-82 by MTT
      (microculture tetrazolium) method. The studies of DNA-binding agree with the
      effects on the inhibition of tumor cells in vitro.

PMID- 19578988
TI  - Identification of camelid specific residues in mitochondrial ATP synthase
      subunits.
AB  - ATP synthase is an enzyme involved in oxidative phosphorylation from prokaryotic
      to eukaryotic cells. In mammals it comprises at least 16 subunits from which the
      mitochondrial encoded ATP6 and ATP8 are essential. Mitochondrial genes variations
      have been suggested to allow rapid human and animal adaptation to new climates
      and dietary conditions (Mishmar et al. 2003). Camelidae taxa are uniquely adapted
      to extremely hot and dry climates of African-Asian territories and to cold and
      hypoxic environments of the South American Andean region. We sequenced and
      analyzed ATP6 and ATP8 genes in all camelid species. Based on the available
      structural data and evolutionary conservation of the deduced proteins we
      identified features proper of the group. In Old World camels the ATP8, important
      in the assembly of the F0 complex, showed a number of positively charged residues
      higher than in the other aligned species. In ATP6 we found the camelid specific
      substitutions Q47H and I106V that occur in sites highly conserved in other
      species. We speculate that these changes may have functional importance.

PMID- 19578989
TI  - Recurrent networks with short term synaptic depression.
AB  - Cortical circuitry shows an abundance of recurrent connections. A widely used
      model that relies on recurrence is the ring attractor network, which has been
      used to describe phenomena as diverse as working memory, visual processing and
      head direction cells. Commonly, the synapses in these models are static. Here, we
      examine the behaviour of ring attractor networks when the recurrent connections
      are subject to short term synaptic depression, as observed in many brain regions.
      We find that in the presence of a uniform background current, the network
      activity can be in either of three states: a stationary attractor state, a
      uniform state, or a rotating attractor state. The rotation speed can be adjusted
      over a large range by changing the background current, opening the possibility to
      use the network as a variable frequency oscillator or pattern generator. Finally,
      using simulations we extend the network to two-dimensional fields and find a rich
      range of possible behaviours.

PMID- 19578990
TI  - Using patient DNA to optimize therapy in heart failure patients: a move toward
      perfection.

PMID- 19578992
TI  - Microfabricated glass devices for rapid single cell immobilization in mouse
      zygote microinjection.
AB  - This paper presents the design and microfabrication of a vacuum-based cell
      holding device for single-cell immobilization and the use of the device in mouse
      zygote microinjection. The device contains many through-holes, constructed via
      two-sided glass wet etching and polydimethylsiloxane (PDMS)-glass bonding.
      Experimental results of mouse zygote immobilization and microinjection
      demonstrate that the device is effective for rapid cell immobilization and does
      not produce negative effect on embryonic development.

PMID- 19578991
TI  - Anti-convulsant effect and mechanism of Astragalus mongholicus extract in vitro
      and in vivo: protection against oxidative damage and mitochondrial dysfunction.
AB  - Astragalus mongholicus (AM) is a traditional medicinal herb used as a
      neuroprotective agent for its anxiolytic, antidepressant, antiamnestic, and
      antiaggresive effects. However, the mechanisms underlying its anti-convulsant
      properties are not well studied. In the present study, we examined the
      anticonvulsant effects on pentylenetetrazol (PTZ)-induced seizures in mice and
      the possible mechanisms of protection against oxidative damage and mitochondrial
      dysfunction in vitro. The behavioral studies showed that the root extract of AM
      had powerful anticonvulsant effects against seizures induced by PTZ and the
      biochemical studies showed that root extract of AM inhibited PTZ-induced increase
      in lipid peroxidation, protein oxidation and reactive oxygen species, and
      enhanced mitochondrial function. Electron spin resonance spectroscopy studies
      demonstrated that the extracts from the root and aerial parts of AM possess
      potent effects on scavenging hydroxyl and lipid free radicals. We found that AM
      extract significantly protected malondialdehyde-induced oxidative damage by
      ameliorating activities of the mitochondrial complexes I, II, malate
      dehydrogenase and mitochondrial membrane potential. These data suggest that the
      anti-convulsant effects of AM extract may be mediated by its protective actions
      against oxidative damage and amelioration of mitochondrial dysfunction.

PMID- 19578993
TI  - Antibacterial activity of Hylomecon hylomeconoides against methicillin-resistant
      Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is serious clinical urgent
      problems worldwide. In the present study, the antibacterial activity of Hylomecon
      hylomeconoides was investigated. The EtOH extract and its fraction (n-hexane,
      CH(2)Cl(2), EtOAc, and H(2)O) were investigated against MRSA. The most active
      extract (CH(2)Cl(2)) led to the isolation of 6-methoxydihydrosanguinarine (6-MS),
      6-acetonylhydrosanguinarine, and dihydrosanguinarine. These compounds were very
      active against MRSA strains with minimum inhibitory concentrations (MICs) ranging
      from 1.95 to 250 microg/ml. Our study did however focus on 6-MS as it appeared to
      be the most active with MICs in the range of 1.9 to 3.9 microg/ml. These results
      encourage us to think that 6-MS can be used as a natural antibacterial agent.

PMID- 19578994
TI  - Characterization of alcohol dehydrogenase from permeabilized brewer's yeast cells
      immobilized on the derived attapulgite nanofibers.
AB  - Alcohol dehydrogenase (ADH) from permeabilized brewer's yeast was immobilized on
      derived attapulgite nanofibers via glutaraldehyde covalent binding. The effect of
      immobilization on ADH activity, optimum temperature and pH, thermal, pH and
      operational stability, reusability of immobilized ADH, and bioreduction of ethyl
      3-oxobutyrate (EOB) to ethyl(S)-3-hydroxybutyrate ((S)-EHB) by the immobilized
      ADH were investigated. The results show the immobilized ADH retained higher
      activity over wider ranges of pH and temperature than those of the free. The
      optimum temperature and pH were 7.5 and 35 degrees C, respectively, and 58% of
      the original activity was retented after incubation at 35 degrees C for 32 h.
      More importantly, in bioreduction of EOB mediated by immobilized ADH, the
      conversion of substrate and enantiomeric excess (ee) of product reached 88% and
      99.2%, respectively, within 2 h and retained about 42% of the initial activity
      after eight cycles.

PMID- 19578995
TI  - Dopamine D1 receptor gene expression studies in unilateral 6-hydroxydopamine
      lesioned Parkinson's rat: effect of 5-HT, GABA, and bone marrow cell
      supplementation.
AB  - Parkinson's disease is the second most common neurodegenerative disorder and
      remains incurable. Many potential compensatory mechanisms have now been proposed;
      these are both dopaminergic, focused on enhancing effects or exposure to existing
      dopamine, and non-dopaminergic, being focused on reducing activity of the
      indirect striatal output pathway. In the present study, the effects of serotonin,
      gamma-aminobutyric acid, and bone marrow cell supplementation intranigrally to
      the substantia nigra on unilateral 6-hydroxydopamine-infused rats were analyzed
      individually. Dopaminergic binding parameters were done by Scatchard analysis of
      dopamine D(1) receptor-binding assay using [(3)H]SCH 23390. In the corpus
      striatum, 6-hydroxydopamine-infused rats showed a significant decrease in B (max)
      (P < 0.001), and in cerebral cortex, they showed a significant increase in B
      (max) (P < 0.001) compared to control. Real-time polymerase chain reaction
      amplification of dopamine D(1) was downregulated (P < 0.001) in the corpus
      striatum of 6-hydroxydopamine-infused rats compared to control, whereas in the
      cerebral cortex, it showed a significant upregulation (P < 0.001). Behavioral
      studies were carried out to confirm the biochemical and molecular studies.
      Serotonin and gamma-aminobutyric acid supplementation reversed these changes to
      control. The bone marrow cell-treated group of our studies does not show much
      significant change as compared to the serotonin and gamma-aminobutyric acid
      supplemented groups. The alterations in dopamine D(1) receptor-binding parameters
      and gene expression during Parkinson's model were reversed by serotonin and gamma
      aminobutyric acid supplementation in our experiments, which has clinical
      significance in the management of the disease.

PMID- 19578996
TI  - Sjogren syndrome or sjogren disease? The histological and immunological bias
      caused by the 2002 criteria.
AB  - The current 2002 classification criteria do not cover the broad clinical and
      immunological heterogeneity of primary Sjogren syndrome (SS), since five of the
      six criteria focus exclusively on glandular involvement and the remaining
      criterion is the mandatory presence of anti-Ro/La antibodies. The aim of this
      study was to analyze the clinical features of patients with a well-established
      diagnosis of primary SS who do not fulfill the 2002 classification criteria. Five
      hundred seven patients diagnosed with primary SS (1993 criteria) were
      consecutively included and followed up. Two hundred twenty-one (44%) patients did
      not fulfill the 2002 criteria. These patients were older at diagnosis (p < 0.001)
      and had a lower frequency of parotid enlargement (p = 0.002), fever (p = 0.041),
      arthritis (p = 0.041), vasculitis (p = 0.050), peripheral neuropathy (p = 0.002),
      cranial nerve involvement (p = 0.015), raised erythrocyte sedimentation rate (
      ESR) levels (p < 0.001), anemia (p < 0.001), leukopenia (p = 0.037),
      hypergammaglobulinemia (p < 0.001), positive rheumatoid factor ( RF; p = 0.002),
      and cryoglobulinemia (p = 0.049) in comparison with those fulfilling 2002
      criteria. However, there were no significant differences in the prevalence of
      sicca features, diagnostic tests, overall systemic involvement, antinuclear
      antibodies , complement levels, development of B-cell lymphoma, or survival.
      Patients with anti-Ro antibodies had the highest frequencies of systemic
      features, hematological abnormalities, and altered immunological markers. In
      conclusion, patients fulfilling the 2002 criteria, who have either a specific
      histological diagnosis (lymphocytic infiltration) or highly specific
      autoantibodies (Ro/La), might well be considered to have Sjogren "disease." In
      contrast, etiopathogenic mechanisms other than lymphocytic-mediated epithelial
      damage could be involved in patients with negative Ro and negative biopsy, in
      whom the term Sjogren "syndrome" seems more adequate.

PMID- 19578998
TI  - Single nucleotide polymorphisms and haplotypic diversity in the bovine PRKAB1
      gene.
AB  - The AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of
      cellular and systemic energy balance. PRKAB1, the gene that encodes the beta1
      regulatory subunit of AMPK, has been shown to be highly involved in the glycogen
      metabolism. To date, several mutations affecting function of human PRKAB1 have
      been identified but few studies have shown a complete description of the
      variability of bovine PRKAB1. In the present study, we report the investigation
      of PRKAB1 genetic polymorphism in a sample of 811 Chinese indigenous bovine
      individuals. The screening of the coding regions with their intron-exon
      boundaries and the proximal flanking regions was performed using a PCR-SSCP
      strategy. Following sequence analysis revealed 29 single nucleotide polymorphisms
      (SNPs) of bovine PRKAB1 gene. Four were in the 5'-UTR; eight were in the coding
      region, among which one was nonsense mutant,one was missense mutant, six were
      synonymous mutation; and seventeen were in the introns. We also investigated
      haplotype frequencies and linkage disequilibrium (LD) coefficients for these SNPs
      in three Chinese indigenous cattle breeds. Three LD blocks were found in Nanyang
      cattle and four common haplotypes were identified based on five SNPs, with the
      most common haplotypes (GGTCC) occurring at a frequency of 82.7%. In Qinchuan
      cattle, one major block and two of the four possible haplotypes were found, one
      main haplotypes (CG) accounted for 93.8% of all possible marker combinations. In
      Jiaxian cattle, two LD blocks were found and four common haplotypes were
      identified based on four SNPs, the most common haplotypes (CCGT) accounted for
      77.4% of the total. Variations detected here might have an impact on PRKAB1
      activity and function and underpin the development of gene markers for bovine
      energy balance and in the glycogen metabolism.

PMID- 19578997
TI  - Insights into the role of the calcium sensing receptor in epidermal
      differentiation in vivo.
AB  - While the important role of calcium (Ca(++)) signaling is fundamental in
      epidermal cell physiology, a detailed knowledge of precisely how epidermal cells
      respond to Ca(++) levels is not clear. Using peptide-specific antibodies that we
      generated, we set out to evaluate the temporal and spatial distribution pattern
      of the Ca(++)-sensing receptor (CaSR) during epidermogenesis and to assess its
      involvement in the mature epidermis (e.g., in acute injury and tumorigenesis).
      Our data indicate a developmentally regulated expression of CaSR: up-regulation
      occurs in specific epidermal cells and cell layers in normal development or in
      response to injury when epidermal cells are induced to undergo commitment and
      early differentiation events, and down-regulation occurs in terminal
      differentiation stages. These results provide a new perspective on the role of
      the CaSR in these processes and describe a novel tool for evaluating Ca(++)
      mediated epidermal differentiation.

PMID- 19578999
TI  - Influence of parasitism on trace element contents in tissues of red fox (Vulpes
      vulpes) and its parasites Mesocestoides spp. (Cestoda) and Toxascaris leonina
      (Nematoda).
AB  - Bioaccumulation of cadmium, chromium, copper, manganese, nickel, lead, and zinc
      in 56 foxes (Vulpes vulpes) and their parasites Mesocestoides spp. (Cestoda) and
      Toxascaris leonina (Nematoda) was studied. The levels of heavy metals were
      determined in the livers and kidneys of the animals depending on parasitism in
      the following ranges: Pb, 0.029-3.556; Cd, 0.055-9.967; Cr, 0.001-0.304; Cu, 4.15
      41.15; Mn, 1.81-19.94; Ni: 0.037-0.831; Zn, 52.0-212.9 microg/g dry weight (dw).
      Cd in parasites (0.038-3.678 microg/g dw) were comparable with those in the
      livers of the host and lower than in the kidneys (0.095-6.032 microg/g dw).
      Contents of Pb, Cr, Cu, Mn, Ni, and Zn in cestodes were predominantly higher than
      those in the kidney and liver of the host. Median lead levels in Mesocestoides
      spp. (45.6 microg/g dw) were 52-fold higher than in the kidney and liver of the
      red fox (Vulpes vulpes) infected by both parasites and median Pb values in T.
      leonina (8.98 microg/g dw) were 8-fold higher than in the tissues of the
      parasitized red fox. Bioaccumulation factors of copper, zinc, nickel, and
      manganese are lower than those of lead and mostly range from 1.9 to 24 for
      Mesocestoides spp. and from 1.5 to 6 for nematode T. leonina depending on the
      tissue of host and element. A significant decrease in the content of Pb was found
      in the kidney of animals infected by T. leonina (0.260 microg/g dw) as well as
      those infected by Mesocestoides spp. (0.457 microg/g dw) in comparison with the
      lead content (0.878 microg/g dw) in the kidneys of the nonparasitized red fox.
      Regardless of a bioaccumulation of copper and manganese in the parasites, a
      significant increase of the concentrations of Mn and Cu was observed in the
      host's livers infected predominantly by Mesocestoides spp.

PMID- 19579001
TI  - Pregabalin for treating paroxysmal painful symptoms in multiple sclerosis: a
      pilot study.

PMID- 19579000
TI  - Risperidone and haloperidol promote survival of stem cells in the rat
      hippocampus.
AB  - Altered neuroplasticity contributes to the pathophysiology of schizophrenia.
      However, the idea that antipsychotics may act, at least in part, by normalizing
      neurogenesis has not been consistently supported. Our study seeks to determine
      whether hippocampal cell proliferation is altered in adult rats pretreated with
      ketamine, a validated model of schizophrenia, and whether chronic administration
      with neuroleptic drugs (haloperidol and risperidone) affect changes of cell
      genesis/survival. Ketamine per se has no effect on cell proliferation. Its
      withdrawal, however, significantly induced cell proliferation/survival in the
      hippocampus. Risperidone and haloperidol supported cell genesis/survival as well.
      During ketamine withdrawal, however, their application did not affect cell
      proliferation/survival additionally. TUNEL staining indicated a cell-protective
      potency of both neuroleptics with respect to a ketamine-induced cell death. As RT
      PCR and Western blot revealed that the treatment effects of risperidone and
      haloperidol seemed to be mediated through activation of VEGF and MMP2. The mRNA
      expression of NGF, BDNF, and NT3 was unaffected. From the respective receptors,
      only TrkA was enhanced when ketamine withdrawal was combined with risperidone or
      haloperidol. Risperidone also induced BCL-2. Ketamine withdrawal has no effect on
      the expression of VEGF, MMP2, or BCL-2. It activated the expression of BDNF. This
      effect was normalized by risperidone or haloperidol. The findings indicate a
      promoting effect of risperidone and haloperidol on survival of young neurons in
      the hippocampus by enhancing the expression of the anti-apoptotic protein BCL-2
      and by activation of VEGF/MMP2, whereby an interference with ketamine and thus a
      priority role of the NMDA system was not evident.

PMID- 19579002
TI  - Cysteine, thiourea and thiocyanate interactions with clays: FT-IR, Mossbauer and
      EPR spectroscopy and X-ray diffractometry studies.
AB  - The present study examined the adsorption of cysteine, thiourea and thiocyanate
      on bentonite and montmorillonite at two different pHs (3.00, 8.00). The
      conditions used here are closer to those of prebiotic earth. As shown by FT-IR,
      Mossbauer and EPR spectroscopy and X-ray diffractometry, the most important
      finding of this work is that cysteine and thiourea penetrate into the interlayer
      of the clays and reduce Fe(3+) to Fe(2+), and as consequence, cystine and c,c'
      dithiodiformamidinium ion are formed. This mechanism resembles that which occurs
      with aconitase. This is a very important result for prebiotic chemistry; we
      should think about clays not just sink of molecules, but as primitive vessels of
      production of biomolecules. At pH 8.00, an increasing expansion was observed in
      the following order for both minerals: thiourea > thiocyanate > cysteine. At pH
      3.00, the same order was not observed and thiourea had an opposite behavior,
      being the compound producing the lowest expansion. Mossbauer spectroscopy showed
      that at pH 8.00, the proportion of Fe(2+) ions in bentonite increased, doubling
      for thiourea, or more than doubling for cysteine, in both clays. However, at pH
      3.00, cysteine and thiourea did not change significantly the relative amount of
      Fe(2+) and Fe(3+) ions, when compared to clays without adsorption. For
      thiocyanate, the amount of Fe(2+) produced was independent of the pH or clay
      used, probably because the interlayers of clays are very acidic and HSCN formed
      does not reduce Fe(3+) to Fe(2+). For the interaction of thiocyanate with the
      clays, it was not possible to identify any potential compound formed. For the
      samples of bentonite and montmorillonite at pH 8.00 with cysteine, EPR
      spectroscopy showed that intensity of the lines due to Fe(3+) decreased because
      the reaction of Fe(3+)/cysteine. Intensity of EPR lines did not change when the
      samples of bentonite at pH 3.00 with and without cysteine were compared. These
      results are in accordance with those obtained using Mossbauer and FT-IR
      spectroscopy.

PMID- 19579003
TI  - Thermostable lipases from the extreme thermophilic anaerobic bacteria
      Thermoanaerobacter thermohydrosulfuricus SOL1 and Caldanaerobacter subterraneus
      subsp. tengcongensis.
AB  - Two novel genes encoding for heat and solvent stable lipases from strictly
      anaerobic extreme thermophilic bacteria Thermoanaerobacter thermohydrosulfuricus
      (LipTth) and Caldanaerobacter subterraneus subsp. tengcongensis (LipCst) were
      successfully cloned and expressed in E. coli. Recombinant proteins were purified
      to homogeneity by heat precipitation, hydrophobic interaction, and gel filtration
      chromatography. Unlike the enzymes from mesophile counterparts, enzymatic
      activity was measured at a broad temperature and pH range, between 40 and 90
      degrees C and between pH 6.5 and 10; the half-life of the enzymes at 75 degrees C
      and pH 8.0 was 48 h. Inhibition was observed with 4-(2-aminoethyl)
      benzenesulfonyl fluoride hydrochloride and phenylmethylsulfonylfluorid indicating
      that serine and thiol groups play a role in the active site of the enzymes. Gene
      sequence comparisons indicated very low identity to already described lipases
      from mesophilic and psychrophilic microorganisms. By optimal cultivation of E.
      coli Tuner (DE3) cells in 2-l bioreactors, a massive production of the
      recombinant lipases was achieved (53-2200 U/l) Unlike known lipases, the purified
      robust proteins are resistant against a large number of organic solvents (up to
      99%) and detergents, and show activity toward a broad range of substrates,
      including triacylglycerols, monoacylglycerols, esters of secondary alcohols, and
      p-nitrophenyl esters. Furthermore, the enzyme from T. thermohydrosulfuricus is
      suitable for the production of optically pure compounds since it is highly S
      stereoselective toward esters of secondary alcohols. The observed E values for
      but-3-yn-2-ol butyrate and but-3-yn-2-ol acetate of 21 and 16, respectively, make
      these enzymes ideal candidates for kinetic resolution of synthetically useful
      compounds.

PMID- 19579004
TI  - Comparison of the photodynamic fungicidal efficacy of methylene blue, toluidine
      blue, malachite green and low-power laser irradiation alone against Candida
      albicans.
AB  - This study was to evaluate specific effects of photodynamic therapy (energy
      density 15.8 J/cm(2), 26.3 J/cm(2) and 39.5 J/cm(2)) using methylene blue,
      toluidine blue and malachite green as photosensitizers and low-power laser
      irradiation on the viability of Candida albicans. Suspensions of C. albicans
      containing 10(6) cells/ml were standardized in a spectrophotometer. For each dye,
      120 assays, divided into four groups according to the following experimental
      conditions, were carried out: laser irradiation in the presence of the
      photosensitizer; laser irradiation only; treatment with the photosensitizer only;
      no exposure to laser light or photosensitizer. Next, serial dilutions were
      prepared and seeded onto Sabouraud dextrose agar for the determination of the
      number of colony-forming units per milliliter (CFU/ml). The results were
      subjected to analysis of variance and the Tukey test (P < 0.05). Photodynamic
      therapy using the photosensitizers tested was effective in reducing the number of
      C. albicans.. The number of CFU/ml was reduced by between 0.54 log(10) and 3.07
      log(10) and depended on the laser energy density used. Toluidine blue, methylene
      blue and malachite green were effective photosensitizers in antimicrobial
      photodynamic therapy against C. albicans, as was low-power laser irradiation
      alone.

PMID- 19579005
TI  - Toluidine blue-mediated photodynamic therapy of oral wound infections in rats.
AB  - The purpose of this study was to examine the effect of toluidine blue (TB)
      mediated photodynamic therapy (PDT) on oral wound infections in rats. The study
      called for a combination treatment of a 1mg/ml solution of TB with a red light at
      three intensity settings of 12 J/cm(2), 24 J/cm(2) and 48 J/cm(2). In the group
      that was given the highest light dose of 48 J/cm(2), an average kill rate of
      approximately 97% was achieved. A lesser killing effect was achieved in the group
      that was subjected to the lowest light dose of 12 J/cm(2), where an average of
      approximately 25% of the bacteria survived. After PDT, the lesions were allowed
      to develop, and the peak size of the lesions was larger in the control group than
      in the test groups, especially for the 48 J/cm(2) group. We also observed that in
      the 24 J/cm(2) and 48 J/cm(2) groups the lesions were of significantly smaller
      size. Our study demonstrated that combined TB-PDT therapy can successfully treat
      oral wound infections in rats. These promising results recommend the use of this
      treatment as a possible alternative to topical anti-microbials in future clinical
      applications.

PMID- 19579006
TI  - Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in
      vivo.
AB  - We previously showed that, in vitro, hyperforin from St. John's wort (Hypericum
      perforatum) inhibits 5-lipoxygenase (5-LO), the key enzyme in leukotriene
      biosynthesis. Here, we demonstrate that hyperforin possesses a novel and unique
      molecular pharmacological profile as a 5-LO inhibitor with remarkable efficacy in
      vivo. Hyperforin (4 mg/kg, i.p.) significantly suppressed leukotriene B(4)
      formation in pleural exudates of carrageenan-treated rats associated with potent
      anti-inflammatory effectiveness. Inhibition of 5-LO by hyperforin, but not by the
      iron-ligand type 5-LO inhibitor BWA4C or the nonredox-type inhibitor ZM230487,
      was abolished in the presence of phosphatidylcholine and strongly reduced by
      mutation (W13A-W75A-W102A) of the 5-LO C2-like domain. Moreover, hyperforin
      impaired the interaction of 5-LO with coactosin-like protein and abrogated 5-LO
      nuclear membrane translocation in ionomycin-stimulated neutrophils, processes
      that are typically mediated via the regulatory 5-LO C2-like domain. Together,
      hyperforin is a novel type of 5-LO inhibitor apparently acting by interference
      with the C2-like domain, with high effectiveness in vivo.

PMID- 19579008
TI  - Purification of Schwann cells from adult rats by differential detachment.
AB  - Differential detachment by collagenase treatment is a new and efficient method
      for Schwann cell (SC) purification. As its effect on adult animals remains
      unclear, we have investigated the possibility of SC purification from adult rats.
      To avoid any systematic bias, Schwann cell purity before and after purification
      were compared by morphology, immunostaining of P75(NTR) and S100 and flow
      cytometric analysis. The final SC purities reached 99% as confirmed by three
      independent analyses SC purity and the cell yields were above 10(6) cells after
      two rounds of purification. The method of differential detachment is also
      suitable for SC purification in adult rats and could be useful for research and
      clinical applications.

PMID- 19579007
TI  - Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production
      by chondrocytes.
AB  - OBJECTIVE AND DESIGN: This study aims to investigate the effects of curcumin
      (Cur) on the extracellular matrix protein metabolism of articular chondrocytes
      and on their production of inflammatory mediators. METHODS: Human chondrocytes in
      alginate beads and human cartilage explants were cultured in the absence or in
      the presence of interleukin (IL)-1beta (10(-11) M) and with or without Cur (5-20
      microM). Nitric oxide (NO) synthesis was measured by the Griess
      spectrophotometric method; prostaglandin (PG) E(2) by a specific
      radioimmunoassay; and IL-6, IL-8, aggrecan (Agg), matrix metalloproteinase (MMP)
      3, and tissue inhibitor of metalloproteinase (TIMP)-1 by specific enzyme
      amplified immunoassays. Proteoglycan degradation was evaluated by the release of
      (35)S-glycosaminoglycans (GAG) from human cartilage explants. RESULTS: In
      alginate beads and cartilage explant models, Cur inhibited the basal and the IL
      1beta-stimulated NO, PGE(2), IL-6, IL-8, and MMP-3 production by human
      chondrocytes in a concentration-dependent manner. The TIMP-1 and the Agg
      productions were not modified. In the basal condition, (35)S-GAG release from
      cartilage explants was decreased by Cur. CONCLUSIONS: Curcumin was a potent
      inhibitor of the production of inflammatory and catabolic mediators by
      chondrocytes, suggesting that this natural compound could be efficient in the
      treatment of osteoarthritis.

PMID- 19579009
TI  - Enhancing immune responses against SARS-CoV nucleocapsid DNA vaccine by co
      inoculating interleukin-2 expressing vector in mice.
AB  - The immunogenicity of SARS-CoV nucleocapsid DNA vaccine and the immunoregulatory
      activity of interleukin-2 (IL-2) were investigated. DNA vaccine plasmids, pcDNA-N
      and pcDNA-IL2, were constructed and inoculated into BALB/c mice with or without
      pcDNA-IL2 by intramuscular injection. Cellular and humoral immune responses were
      assessed by indirect ELISA, lymphocyte proliferation assays, ELISPOT and FACS.
      The nucleocapsid DNA vaccine had good immunogenicity and can induce specific
      humoral and cellular immunity in BALB/c mice, while IL-2 plays an immunoadjuvant
      role and enhances specific immune responses. This study provides a frame of
      reference for the design of DNA vaccines against SARS-CoV.

PMID- 19579010
TI  - Design and characterization of a maltose binding protein-linked growth factor for
      matrix engineering.
AB  - The maltose-binding protein (MBP), which possesses a large number of exposed
      hydrophobic zones, can be used as a link for the immobilization of growth
      factors. The amount of immobilized MBP-vascular endothelial growth factors
      (VEGFs) for polystyrene surface was increased with respect to increasing protein,
      showing 1019 ng/cm(2) at 100 microg protein/ml. The phosphorylation of VEGF
      receptors in the MBP-VEGF stimulated HEK293/KDR cells as depicted from western
      blot analysis. Cell adhesion to a MBP-VEGF immobilized surface was mediated by
      the VEGF-VEGFR interaction. These results suggest that MBP-VEGFs are active and a
      MBP immobilization system can then anchor various bioactive proteins to
      hydrophobic surfaces.

PMID- 19579011
TI  - Molecular phylogeny, long-term evolution, and functional divergence of flavin
      containing monooxygenases.
AB  - Flavin-containing monooxygenases (FMOs) metabolize xenobiotic compounds, many of
      which are clinically important, as well as endogenous substrates as part of a
      discrete physiological process. The FMO gene family is conserved and ancient with
      representatives present in all phyla so far examined. However, there is a lack of
      information regarding the long-term evolution and functional divergence of these
      proteins. This study represents the first attempt to characterize the long-term
      evolution followed by the members of this family. Our analysis shows that there
      is extensive silent divergence at the nucleotide level suggesting that this
      family has been subject to strong purifying selection at the protein level.
      Invertebrate FMOs have a polyphyletic origin. The functional divergence of FMOs 1
      5 started before the split between amphibians and mammals. The vertebrate FMO5 is
      more ancestral than other four FMOs. Moreover, the existence of higher levels of
      codon bias was detected at the N-terminal ends, which can be ascribed to the
      critical role played by the FAD binding motif in this region. Finally, critical
      amino acid residues for FMO functional divergence (type I & II) after gene
      duplication were detected and characterized.

PMID- 19579012
TI  - Treatment of venous thromboembolism: guidelines translated for the clinician.
AB  - Venous thromboembolism is a major cause of morbidity and mortality affecting over
      2 million people in the United States each year. The American College of Chest
      Physicians (ACCP) published their first consensus statement on antithrombotic
      therapy in 1986, and the most recent guidelines from the ACCP on this topic were
      released in 2008. We aim to summarize the most recent ACCP guidelines on therapy
      for venous thromboembolism with practical application and interpretation for the
      practicing physician. We will briefly review the rating system used in the
      guidelines for the level of evidence and the strength of the recommendation. We
      will then discuss the recommendations for initial anticoagulant therapies
      including low molecular weight heparin, unfractionated heparin, and fondaparinux
      for patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). A
      discussion of the guidelines on duration of anticoagulant therapy with a vitamin
      K antagonist is also included. In addition, we will address the use of
      thrombolytic therapy and inferior vena cava filter placement for DVT and PE.
      Prevention of postphlebitic syndrome is discussed as well. We will conclude with
      a brief discussion of future directions including several novel therapeutic
      anticoagulants.

PMID- 19579013
TI  - Anatomic and metabolic imaging of venous thromboembolism mimicking thyroid
      carcinoma extension.
AB  - Tumor thrombus arising from malignancies has been well recognized by both
      anatomic and metabolic imaging modalities, including FDG-PET. Recently, venous
      thromboembolism accumulating FDG has also been reported by a few literatures.
      However, blood thrombus accumulating radioiodine has never been reported by now.
      This case presents a follicular thyroid carcinoma patient with venous
      thromboembolism in the left brachiocephalic vein and superior vena cava, which
      could accumulate both FDG and radioiodine, mimicking thyroid carcinoma extension.

PMID- 19579014
TI  - Small (< or = 2 cm) atypical hepatic haemangiomas in the non-cirrhotic patient:
      pattern-based classification scheme for enhancement at triple-phase helical CT.
AB  - PURPOSE: The aim of this study was to determine by triplephase helical computed
      tomography (CT) the appearance of atypical small (< or = 2 cm) hepatic
      haemangiomas (HHs) in the non-cirrhotic patient. MATERIALS AND METHODS: We
      retrospectively reviewed the hepatic arterial-dominant phase (HAP), portal venous
      phase (PVP) and delayed-phase (DP) helical CT images of 47 patients with 52
      atypical small (< or = 2 cm) HHs associated with 34 typical small HHs. Images
      were assessed to identify the patterns of enhancement of atypical HHs and
      correlate their appearance with that of typical small HHs in the delayed phase.
      Interobserver variability and kappa value were calculated. Statistical
      significance was calculated by the Fisher exact test. RESULTS: The 52 atypical
      small HHs were categorised as follows: type 1a (hyperattenuating in the HAP,
      n=17), type 1b [hyperattenuating with transient hepatic attenuation difference
      (THAD) around the lesion in the HAP, n=12], type 2a (homogeneously
      hypoattenuating in the HAP or PVP, n=9), type 2b (hypoattenuating with "bright
      dot" sign in the HAP or PVP, n=13) and type 3 (hypoattenuating with central
      enhancing area, n=1). Interobserver agreement was perfect for HHs of types 1a,
      1b, 2a and 3. On DP images, the appearance of atypical small HHs was identical to
      that of typical small HHs in all cases (p<0.0001), with lesions showing
      homogeneous isoattenuation to the aorta or liver parenchyma without peripheral
      capsule. CONCLUSIONS: Triple-phase helical CT scans can distinguish several types
      of atypical small HHs. The demonstration of patterns similar to those of typical
      forms on DP CT is fundamental for the diagnosis.

PMID- 19579015
TI  - Accuracy of early and delayed FDG PET-CT and of contrast-enhanced CT in the
      evaluation of lung nodules: a preliminary study on 30 patients.
AB  - PURPOSE: The aim of our prospective study was to compare the diagnostic accuracy
      of early, delayed and dual-time-point positron emission tomography (PET)
      acquisition with contrast enhanced computed tomography (CT) within a PET-CT
      examination in the evaluation of pulmonary solitary nodules (SPNs). MATERIALS AND
      METHODS: Thirty patients were enrolled in the study. All the patients underwent a
      dual-time-point PET-CT examination. Whole-body PET images were acquired at 50 min
      after fluorine18-fluorodeoxyglucose ((18)F-FDG) administration (early), followed
      by a chest acquisition (delayed). Lung nodules with maximum standardised uptake
      value SUVmax > or =2.5 were considered malignant. SUVmax was calculated on early
      and delayed images; SUV increasing > or =10% (Delta SUVmax) was considered
      suggestive of malignancy. Absence of significant lung nodule enhancement (<15
      Delta HU) at CT was considered strongly predictive of benignity. For the CT
      morphological assessment, the irregularity of the shape of each lesion was rated.
      PET-CT results were related to histological assays and clinical records.
      Diagnostic accuracy was assessed by area under the receiveroperarting
      characteristic (ROC) curves analysis. RESULTS: Early and delayed SUVmax of
      malignant nodules were significantly higher than those of benign disease. Early
      SUVmax sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) were 77%, 91%, 79.5% and 66.7%; delayed SUVmax
      corresponding values were 77%, 66%, 74% and 66%; dual-time-point SUVmax values
      were 83%, 67%, 75% and 74%; DeltaHU values were 94%, 34%, 67%, 96%; CT
      morphologic evaluation values were 61%, 46%, 60%, 47%. Area under the curve (AUC)
      for early SUVmax was 0.79, for delayed SUVmax 0.80, for dual-time-point SUVmax
      0.85, for DeltaHU 0.63 and for CT morphologic assessment 0.58. CONCLUSIONS: In
      our small series of patients, early and delayed SUVmax showed comparable
      accuracies, whereas morphological and contrast enhanced CT evaluations showed the
      lowest accuracies. Dual-time-point SUVmax showed the largest AUC. However, dual
      time-point SUVmax was most sensitive, whereas single-time-point SUVmax was most
      specific.

PMID- 19579017
TI  - Potato virus X coat protein fusion to human papillomavirus 16 E7 oncoprotein
      enhance antigen stability and accumulation in tobacco chloroplast.
AB  - Cervical cancer linked to infection with human papillomavirus (HPV) is the third
      cause of cancer-related death in women. As the virus cannot be propagated in
      culture, vaccines have been based on recombinant antigens with inherited high
      cost production. In a search of alternative cheap production system, E7 HPV type
      16 protein, an attractive candidate for anticancer vaccine development, was
      engineered to be expressed in tobacco chloroplast. In addition, E7 coding
      sequence was fused to potato virus X coat protein (CP) to compare expression
      level. Results show that E7CP transcript accumulation reached lower levels than
      non-fused E7. However, antigen expression levels were higher for fusion protein
      indicating that CP stabilizes E7 peptide in the chloroplast stroma. These results
      support viability of transplastomic plants for antigen production and the
      relevance of improving recombinant peptide stability for certain transgenes to
      enhance protein accumulation in this organelle.

PMID- 19579016
TI  - Leukocyte recruitment and ischemic brain injury.
AB  - Leukocytes are recruited into the cerebral microcirculation following an ischemic
      insult. The leukocyte-endothelial cell adhesion manifested within a few hours
      after ischemia (followed by reperfusion, I/R) largely reflects an infiltration of
      neutrophils, while other leukocyte populations appear to dominate the adhesive
      interactions with the vessel wall at 24 h of reperfusion. The influx of rolling
      and adherent leukocytes is accompanied by the recruitment of adherent platelets,
      which likely enhances the cytotoxic potential of the leukocytes to which they are
      attached. The recruitment of leukocytes and platelets in the postischemic brain
      is mediated by specific adhesion glycoproteins expressed by the activated blood
      cells and on cerebral microvascular endothelial cells. This process is also
      modulated by different signaling pathways (e.g., CD40/CD40L, Notch) and cytokines
      (e.g., RANTES) that are activated/released following I/R. Some of the known risk
      factors for cardiovascular disease, including hypercholesterolemia and obesity
      appear to exacerbate the leukocyte and platelet recruitment elicited by brain
      I/R. Although lymphocyte-endothelial cell and -platelet interactions in the
      postischemic cerebral microcirculation have not been evaluated to date, recent
      evidence in experimental animals implicate both CD4+ and CD8+ T-lymphocytes in
      the cerebral microvascular dysfunction, inflammation, and tissue injury
      associated with brain I/R. Evidence implicating regulatory T-cells as
      cerebroprotective modulators of the inflammatory and tissue injury responses to
      brain I/R support a continued focus on leukocytes as a target for therapeutic
      intervention in ischemic stroke.

PMID- 19579018
TI  - The cytotoxic activity of the phage E protein suppress the growth of murine B16
      melanomas in vitro and in vivo.
AB  - Novel treatment modalities, including gene therapy, are needed for patients with
      advanced melanoma. The E gene from the phage varphiX174 encodes a 91-aa protein
      which lyses Escherichia coli by formation of a transmembrane tunnel structure. To
      evaluate whether this E gene has a cytotoxic impact on melanoma cells in vitro
      and in vivo, and could therefore be used as a new therapeutic strategy for this
      tumor type, we selected the B16-F10 murine melanoma cell line as a model. We used
      a nonviral gene delivery approach (pcDNA3.1/E plasmid) to study the inhibition of
      melanoma cells' proliferation in vitro and direct intratumoral injection of
      pcDNA3.1/E complexed with jetPEI to deliver E cDNA to rapidly growing murine
      melanomas, and found that the E gene has both a strong antiproliferative effect
      in B16-F10 cells in vitro and induces an efficient decrease in melanoma tumor
      volume in vivo (90% in 15 days). Interestingly, the GFP-E fusion protein
      expressed in melanoma cells was located in the mitochondria. In vitro and in vivo
      analysis demonstrated significant functional and morphological mitochondrial
      alterations accompanied by a significant increase of cytochrome c and active
      caspase-3 and -9 in transfected cells, which suggests that tumoral cell death is
      mediated by the mitochondrial apoptotic pathway. These results show that E gene
      expression in melanoma cells has an extraordinary antitumor effect, which means
      it may be a new candidate for an effective strategy for melanoma treatment.

PMID- 19579019
TI  - Rapid analysis of organic farming insecticides in soil and produce using ultra
      performance liquid chromatography/tandem mass spectrometry.
AB  - A new method for the analysis of three ecological insecticides, namely
      azadyrachtin, spinosad (sum of spinosyn A and spinosyn D) and rotenone, in
      produce and soil samples is presented. Investigated compounds are one of the most
      significant insecticides authorized for organic farming crop protection in many
      countries. Extraction of the pesticides from plant and soil matrices was
      performed by using a modified quick, easy, cheap, effective, rugged, and safe
      (QuEChERS) method. The method entailed a single extraction of the investigated
      compounds with acidified acetonitrile followed by a dispersive solid-phase
      extraction cleanup step prior to the final determination by reverse-phase ultra
      performance liquid chromatography/tandem quadrupole mass spectrometry (UPLC
      MS/MS). Validation studies were carried out on cabbage, tomato and soil samples.
      Recoveries of the spiked samples were in the range between 67% and 108%,
      depending on the matrix and the spiking level. Relative standard deviations for
      all matrix-compound combinations did not exceed 12%. The limits of quantification
      were < or = 0.01 mg kg(-1) in all cases, except for azadirachtin. The developed
      method was applied to the analysis of real samples originating from organic
      farming production.

PMID- 19579020
TI  - Use of Fourier transform infrared spectroscopy and chemometrics to discriminate
      clinical isolates of bacteria of the Burkholderia cepacia complex from different
      species and ribopatterns.
AB  - A methodology for the discrimination of Burkholderia cepacia complex (Bcc)
      clinical isolates at the species level and at the ribopattern level using Fourier
      transform infrared (FTIR) spectroscopy and chemometrics analysis was assessed in
      this study. Different Bcc sequential isolates collected at the Santa Maria
      Hospital (HSM), in Portugal, from clinically infected cystic fibrosis (CF)
      patients were previously classified by established molecular methods at the
      species level and differentiated at the strain level, based on their
      ribopatterns. A set of 185 of these isolates, representing four different Bcc
      species (Burkholderia cepacia, Burkholderia cenocepacia (recA lineages III-A and
      III-B), Burkholderia multivorans and Burkholderia stabilis), was analyzed by FTIR
      and results were processed with chemometric methods. Ten reference strains of
      these species were used to test the FTIR method. The discrimination at the
      species level led to misclassification error rates of 10% and 32% for the HSM
      isolates and reference strains, respectively, clearly indicating that the FTIR
      classification method was unable to generalize results for the reference strains.
      Infrared spectra of HSM isolates were further analyzed in terms of the
      discrimination according to the ribopattern. Results showed misclassification
      error rates of 4%, 2%, and 8% for B. cepacia, B. cenocepacia III-A, and B.
      cenocepacia III-B ribopatterns, respectively. These results demonstrated good
      FTIR spectroscopy discrimination capacity at the ribopattern level, for the HSM
      isolates but showed difficulty at the species level, especially when the
      reference strains were included. Remarkably, this methodology was found to
      discriminate isolates belonging to the same species and ribopattern that were
      collected from the same patient during prolonged colonization, opening the door
      to the identification of chemical modifications resulting from adaptation
      strategies to the CF lung stressing environment, in particular to aggressive and
      prolonged antibiotic therapy.

PMID- 19579021
TI  - Tactile perception of roughness: raised-dot spacing, density and disposition.
AB  - Recently, we showed that tactile speed estimates are modified by the spatial
      parameters of moving raised-dot surfaces, specifically dot spacing but not dot
      disposition (regular, irregular) or density. The purpose of this study was to
      determine the extent to which tactile roughness perception resembles tactile
      speed with respect to its dependence and/or independence of the spatial
      properties of raised-dot surfaces. Subjects scaled the roughness of surfaces
      displaced under the finger. Dot spacing (centre-to-centre) ranged from 1.5 to 8.5
      mm in the direction of the scan (longitudinal). Mean dot density varied from 2.2
      to 46.2 dots/cm2. Dot disposition was varied: repeating rows (periodic) or quasi
      random (non-periodic). In the first experiment (n = 8), the periodic and non
      periodic surfaces were matched for mean dot density. Roughness showed a monotonic
      increase with 1/dot density, but non-periodic surfaces were judged to be smoother
      than the periodic surfaces. Subjective equality was obtained when the data were
      re-expressed relative to longitudinal SP. In the second experiment (n = 7), the
      periodic and non-periodic surfaces were matched for longitudinal dot spacing.
      Perceptual equivalence was observed when the results were plotted relative to dot
      spacing, but not 1/dot density. Dot spacing in the orthogonal direction
      (transverse) was excluded as a contributing factor. Thus, as found for tactile
      speed scaling, roughness is critically dependent on longitudinal dot spacing, but
      independent of dot disposition and dot density (over much of the tested range).
      These results provide a set of predictions to identify cortical neurones that
      play critical roles in roughness appreciation.

PMID- 19579022
TI  - Probing the membrane potential of living cells by dielectric spectroscopy.
AB  - In this paper we demonstrate a quantitative way to measure the membrane potential
      of live cells by dielectric spectroscopy. We also show that the values of the
      membrane potential obtained using our technique are in good agreement with those
      obtained using traditional methods-voltage-sensitive dyes. The membrane potential
      is determined by fitting the experimental dielectric dispersion curves with the
      dispersion curves obtained from a theoretical model. Variations in the membrane
      potential were induced by modifying the concentration of potassium chloride in
      the solution of the cell suspension in the presence of valinomycin. For
      exemplification of the method, E. coli was chosen for our experiments.

PMID- 19579023
TI  - Critical stresses for cancer cell detachment in microchannels.
AB  - We present experiments involving cancer cells adhering to microchannels,
      subjected to increasing shear stresses (0.1-30 Pa). Morphological studies were
      carried out at different shear stresses. Cells exhibit spreading patterns similar
      to those observed under static conditions, as long as the shear stress is not too
      high. At critical wall shear stresses (around 2-5 Pa), cell-substrate contact
      area decreases until detachment at the larger stresses. Critical shear stresses
      are found to be lower for higher confinements (i.e. smaller cell height to
      channel height ratio). Fluorescent techniques were used to locate focal adhesions
      (typically 1 lm(2) in size) under various shearing conditions, showing that cells
      increase the number of focal contacts in the region facing the flow. To analyze
      such data, we propose a model to determine the critical stress, resulting from
      the competition between hydrodynamic forces and the adhesive cell resistance.
      With this model, typical adhesive stresses exerted at each focal contact can be
      determined and are in agreement with previous works.

PMID- 19579024
TI  - Multicenter phase 2 study of induction chemotherapy with docetaxel and nedaplatin
      for oral squamous cell carcinoma.
AB  - PURPOSE: To determine the clinical and hisotological efficacy and toxicities of
      induction chemotherapy with docetaxel (DOC) and nedaplatin (CDGP) for oral
      squamous cell carcinoma (OSCC) in the preoperative setting. METHODS: A total of
      30 patients with locally advanced but operable OSCC were enrolled. Combination
      induction chemotherapy consisted of DOC 60 mg/m2 followed by CDGP 100 mg/m2.
      RESULTS: All patients received one cycle of chemotherapy. In the clinical
      assessment, ten patients achieved partial response for an overall response rate
      of 33.3% (95% CI, 16.4-50.2%). Histological assessment of surgical specimens
      showed an overall response rate of 56.6% (95% CI, 38.9-74.3%). Although severe
      neutropenia was observed in 90% of patients, only one patient (3.3%) experienced
      severe infection. Toxicities associated with this regimen did not interfere with
      planned radical surgery. CONCLUSIONS: A single cycle of preoperative combination
      chemotherapy with DOC and CDGP showed moderate histological activity with an
      acceptable safety profile for the planned radical surgery. Further studies
      testing more cycles before surgery might be more appropriate.

PMID- 19579025
TI  - CYP1A2 genotype and rheumatoid arthritis in Koreans.
AB  - Cytochrome P540 (CYP) 1A2 plays a role in the production of reactive oxygen
      species (ROS), which have been implicated in the development of rheumatoid
      arthritis (RA). The objective of this study was to investigate the association
      between a common polymorphism in the CYP1A2 gene with risk and severity of RA in
      a Korean population. Cases (n = 1321) with RA and controls (n = 1037) were
      genotyped for the CYP1A2 -163 A>C polymorphism by real-time PCR. HLA-DRB1 typing
      and further subtyping of all alleles was performed by PCR, sequence-specific
      oligonucleotide probe hybridization and direct DNA sequencing analysis. The odds
      ratio (OR) [(95% confidence interval (CI)] of RA associated with the low
      inducible C allele was 1.11 (0.80-1.55) among non-shared epitope (SE) carriers,
      0.82 (0.56-1.20) among heterozygotes and 0.32 (0.10-1.04) among individuals
      homozygous for the SE (P = 0.03 for CYP1A2-SE interaction). A protective effect
      of the low inducibility CYP1A2 C allele among carriers of the SE suggests that a
      product of CYP1A2-mediated metabolism, such as ROS, may be involved in the
      development of RA.

PMID- 19579026
TI  - Abatacept as an option therapy in difficult to treat psoriatic arthritis.
AB  - Psoriatic arthritis (PA) is an inflammatory arthritis associated with cutaneous
      psoriasis. Treatment consists of non-steroidal anti-inflammatory drugs,
      corticosteroids at low doses and disease-modifying anti-rheumatic drugs. We
      relate a case of PA that after the fault of the handlings convecionais to sick we
      opted for an empiric treatment with Abatacept, based on the current knowledge on
      the physiopathology of PA and its low hepatotoxicity found in an animal model.

PMID- 19579027
TI  - MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA.
AB  - PFAPA is a periodic fever disease, of unknown etiology, characterized by aphthous
      stomatitis, pharyngitis and cervical adenitis. To inquire whether genes
      implicated in other auto-inflammatory diseases might be involved in its
      pathogenesis, predominant mutations in the genes causing familial Mediterranean
      fever, TNF receptor-associated periodic fever syndrome, Crohn's disease and
      Muckel-Wells syndrome were analyzed in PFAPA patients. Patients (n = 57) with
      PFAPA, according to previously published criteria were recruited, at the Meyer
      Children Hospital during 2006-2007. Clinical information was complemented during
      physicians-parents encounter. Predominant mutations in MEFV, TNF1rA, CARD15/NOD2
      and NLRP3 genes were tested. Mean age at diagnosis was 30.64 +/- 16.4 months.
      Boys (n = 33; 58%) were diagnosed earlier than girls (n = 21; 42%) at 26.18 +/-
      13.83 and 36.41 +/- 18.32 months, respectively (P = 0.05). Fifteen patients (27%)
      carried an MEFV mutation; two patients (3.6%) a CARD15 mutation, one patient
      (1.8%) a variance in TNF1rA and another had both an MEFV and a CARD15 mutation.
      Clinical symptoms were equally manifested in carriers and non-carriers. The high
      carrier rate of MEFV mutations in our PFAPA cases compares well with that of the
      general population in Israel. It is debated whether MEFV mutations, when mediated
      by the presence of additional modifiers, may expose a transient fever condition,
      namely PFAPA.

PMID- 19579028
TI  - Myocarditis as a form of relapse in two patients with adult Still's disease.
AB  - Still's disease is a subset of juvenile idiopathic arthritis (JIA) that usually
      presents with intermittent fever, rash, and arthritis. Extra-articular flares can
      occur several years after disease onset. We report two cases of adult Still's
      disease with myocarditis after several years of being in remission. A 34-year-old
      Caucasian man with history of systemic juvenile arthritis in remission since age
      13 was admitted in hospital with 10 days history of fever, odynophagia, and
      arthralgias. Chest X-ray and cardiac ultrasound showed cardiac enlargement. An
      endomyocardial biopsy revealed acute myocarditis. He was treated with
      methylprednisolone and intravenous gammaglobulin, with improvement of his general
      condition and cardiac parameters. A 16-year-old Caucasian male patient with
      history of systemic JIA in remission for the last 7 years was admitted with 7
      days history of fever, odynophagia, arthralgias, and myalgias. Two days after
      admission, he developed chest pain and pericardial rubbing was found on
      examination. Cardiac ultrasound showed left ventricular dilatation with impaired
      systolic function, and posterior, inferior and apical-septal wall hypokinesia.
      Blood test showed elevated creatine phosphokinase levels. He was treated with IV
      methylprednisolone with normal follow-up cardiac ultrasound. Cardiac involvement
      in patients with systemic JIA can be the first symptom of disease reactivation,
      even after many years of disease remission.

PMID- 19579029
TI  - Association of chronic non-bacterial osteomyelitis with Crohn's disease but not
      with CARD15 gene variants.
AB  - Chronic non-bacterial osteomyelitis (CNO) is an inflammatory, non-infectious
      disorder of the skeletal system with unknown etiology. Besides bone-inflammation,
      patients may present with inflammatory involvement of other tissues. Chronic
      recurrent multifocal osteomyelitis (CRMO) is the most severe form of CNO. We
      describe the occurrence of Crohn's disease (CD) in four patients, previously
      diagnosed with CRMO. Mutations in CARD15, encoding the NOD2 protein, have
      recently been found in patients with CD. Based on the occurence of CNO and CD in
      these four and several reported patients, we hypothesized that CD and CRMO might
      share a common autoinflammatory process. Thus, we searched for CD associated
      CARD15 gene variants R702W, G908R and 1007fs in 29 CNO patients, 4 of them
      additionally diagnosed with CD. In the latter one out of the four showed compound
      heterozygosity for the gene variants R702W and 1007fs. The allele frequency in
      the 25 patients diagnosed with CNO but not CD was not different from that already
      reported in healthy people (R702W 4.0%, G908R 2.0%, 1007fs 2.0%). The occurrence
      of non-bacterial bone inflammation and granulomatous intestinal inflammation
      seems to represent an extended phenotype of CD, which partly might be explained
      by potential disease causing mutations in CARD15. However, CNO without intestinal
      inflammation is not associated with common CARD15 gene variants. Therefore, other
      variants of genes coding for proteins involved in innate immunity and
      inflammation might predispose for the occurrence of CNO.

PMID- 19579030
TI  - Glaucoma detection and evaluation through pattern recognition in standard
      automated perimetry data.
AB  - BACKGROUND: Perimetry remains one of the main diagnostic tools in glaucoma, and
      it is usually used in conjunction with evaluation of the optic nerve. This study
      assesses the capability of automatic pattern recognition methods, and in
      particular the support vector machines (SVM), to provide a valid clinical
      diagnosis classification of glaucoma based solely upon perimetry data. METHODS:
      Over 2,200 patient records were reviewed to produce an annotated database of
      2,017 eyes. Visual field (VF) data were obtained with HFA II perimeter using the
      24-2 algorithm. Ancillary information included treated and untreated intraocular
      pressure, cup-to-disk ratio, age, sex, central corneal thickness and family
      history. Ophthalmic diagnosis and classification of visual fields were provided
      by a consensus of at least two glaucoma experts. The database includes normal
      eyes, cases of suspect glaucoma, pre-perimetric glaucoma, and glaucoma with
      different levels of severity, as well as 189 eyes with neurologic or neuro
      ophthalmologic defects. Support vector machines were trained to provide multi
      level classifications into visual field and glaucoma diagnosis classes. RESULTS:
      Numerical validation indicates 70-90% expected agreement between multi-stage
      classifications provided by the automated system, using a hierarchy of SVM
      models, and glaucoma experts. Approximately 75% accuracy for the classification
      of glaucoma suspect and pre-perimetric glaucoma (which by definition do not
      exhibit glaucomatous defects) indicates the ability of the numerical model to
      discern subtle changes in the VF associated with early stages of glaucoma. The
      Glaucoma Likelihood Index provides a single number summary of classification
      results. CONCLUSIONS: Automatic classification of perimetry data may be useful
      for glaucoma screening, staging and follow-up.

PMID- 19579032
TI  - Modelled temperature-dependent excitability behaviour of a generalised human
      peripheral sensory nerve fibre.
AB  - The objective of this study was to determine if a recently developed human
      Ranvier node model, which is based on a modified version of the Hodgkin-Huxley
      model, could predict the excitability behaviour in human peripheral sensory nerve
      fibres with diameters ranging from 5.0 to 15.0 microm. The Ranvier node model was
      extended to include a persistent sodium current and was incorporated into a
      generalised single cable nerve fibre model. Parameter temperature dependence was
      included. All calculations were performed in Matlab. Sensory nerve fibre
      excitability behaviour characteristics predicted by the new nerve fibre model at
      different temperatures and fibre diameters compared well with measured data.
      Absolute refractory periods deviated from measured data, while relative
      refractory periods were similar to measured data. Conduction velocities showed
      both fibre diameter and temperature dependence and were underestimated in fibres
      thinner than 12.5 microm. Calculated strength-duration time constants ranged from
      128.5 to 183.0 micros at 37 degrees C over the studied nerve fibre diameter
      range, with chronaxie times about 30% shorter than strength-duration time
      constants. Chronaxie times exhibited temperature dependence, with values
      overestimated by a factor 5 at temperatures lower than body temperature. Possible
      explanations include the deviated absolute refractory period trend and inclusion
      of a nodal strangulation relationship.

PMID- 19579031
TI  - TRPV2 expression in rat oral mucosa.
AB  - The oral mucosa is a highly specialised, stratified epithelium that confers
      protection from infection and physical, chemical and thermal stimuli. The non
      keratinised junctional epithelium surrounds each tooth like a collar and is
      easily attacked by foreign substances from the oral sulcus. We found that TRPV2,
      a temperature-gated channel, is highly expressed in junctional epithelial cells,
      but not in oral sulcular epithelial cells or oral epithelial cells. Dual or
      triple immunolabelling with immunocompetent cell markers also revealed TRPV2
      expression in Langerhans cells and in dendritic cells and macrophages. Electron
      microscopy disclosed TRPV2 immunoreactivity in the unmyelinated and thinly
      myelinated axons within the connective tissue underlying the epithelium. TRPV2
      labelling was also observed in venule endothelial cells. The electron-dense
      immunoreaction in junctional epithelial cells, macrophages and neural axons
      occurred on the plasma membrane, on invaginations of the plasma membrane and in
      vesicular structures. Because TRPV2 has been shown to respond to temperature,
      hypotonicity and mechanical stimuli, gingival cells expressing TRPV2 may act as
      sensor cells, detecting changes in the physical and chemical environment, and may
      play a role in subsequent defence mechanisms.

PMID- 19579034
TI  - Small-scale indirect effects determine the outcome of a tripartite plant
      disperser-granivore interaction.
AB  - The microhabitat in which plants grow affects the outcome of their interactions
      with animals, particularly non-specialist consumers. Nevertheless, as most
      research on this topic has dealt with either mutualists or antagonists, little is
      known about the indirect effects of plant microhabitats on the outcome of
      tripartite interactions involving plants and both mutualists (e.g. seed
      dispersers) and antagonists (e.g. granivores). During three consecutive years, we
      analysed small-scale variations in the interaction of a perennial myrmecochore,
      Helleborus foetidus, with its seed dispersers and consumers as a function of the
      intensity of plant cover. Most seeds were released during the day and were
      rapidly removed by ants. Nevertheless, the proportion of ant-removed seeds was
      higher for plants located in open microhabitats than for plants surrounded by
      dense vegetation and rocky cover. Ant sampling revealed that seed removers were
      equally abundant, irrespective of the level of cover. By contrast, a few tiny ant
      species that feed on the reward without transporting the seeds were more abundant
      in highly covered microhabitats, irrespective of hellebore diaspore availability.
      These "cheaters" decrease the chance of removal by removers and increase the
      probability of seeds remaining on the ground until night, when granivore mice
      Apodemus sylvaticus become active. Mice also preferred foraging in covered
      microhabitats, where they consumed a larger proportion of seeds. Therefore, the
      density of cover indirectly increased seed predation risk by attracting more seed
      predators and cheater ants that contribute to increase seed availability for seed
      predators. Our results emphasize the importance of considering the indirect
      effects of plant microhabitat on their dispersal success. They highlight the
      indirect effect of cheaters that are likely to interfere in mutualisms and may
      lead to their collapse unless external factors such as spatio-temporal
      heterogeneity in seed availability constrain their effect.

PMID- 19579033
TI  - Identification and characterization of HTD2: a novel gene negatively regulating
      tiller bud outgrowth in rice.
AB  - Tiller number is highly regulated by controlling the formation of tiller bud and
      its subsequent outgrowth in response to endogenous and environmental signals.
      Here, we identified a rice mutant htd2 from one of the 15,000 transgenic rice
      lines, which is characterized by a high tillering and dwarf phenotype. Phenotypic
      analysis of the mutant showed that the mutation did not affect formation of
      tiller bud, but promoted the subsequent outgrowth of tiller bud. To isolate the
      htd2 gene, a map-based cloning strategy was employed and 17 new insertions
      deletions (InDels) markers were developed. A high-resolution physical map of the
      chromosomal region around the htd2 gene was made using the F(2) and F(3)
      population. Finally, the gene was mapped in 12.8 kb region between marker HT41
      and marker HT52 within the BAC clone OSJNBa0009J13. Cloning and sequencing of the
      target region from the mutant showed that the T-DNA insertion caused a 463 bp
      deletion between the promoter and first exon of an esterase/lipase/thioesterase
      family gene in the 12.8 kb region. Furthermore, transgenic rice with reduced
      expression level of the gene exhibited an enhanced tillering and dwarf phenotype.
      Accordingly, the esterase/lipase/thioesterase family gene (TIGR locus Os03g10620)
      was identified as the HTD2 gene. HTD2 transcripts were expressed mainly in leaf.
      Loss of function of HTD2 resulted in a significantly increased expression of
      HTD1, D10 and D3, which were involved in the strigolactone biosynthetic pathway.
      The results suggest that the HTD2 gene could negatively regulate tiller bud
      outgrowth by the strigolactone pathway.

PMID- 19579035
TI  - Dispersal and life history strategies in epiphyte metacommunities: alternative
      solutions to survival in patchy, dynamic landscapes.
AB  - Host trees for obligate epiphytes are dynamic patches that emerge, grow and fall,
      and metacommunity diversity critically depends on efficient dispersal. Even
      though species that disperse by large asexual diaspores are strongly dispersal
      limited, asexual dispersal is common. The stronger dispersal limitation of
      asexually reproducing species compared to species reproducing sexually via small
      spores may be compensated by higher growth rates, lower sensitivity to habitat
      conditions, higher competitive ability or younger reproductive age. We compared
      growth and reproduction of different groups of epiphytic bryophytes with
      contrasting dispersal (asexual vs. sexual) and life history strategies
      (colonists, short- and long-lived shuttle species, perennial stayers) in an old
      growth forest stand in the boreo-nemoral region in eastern Sweden. No differences
      were seen in relative growth rates between asexual and sexual species. Long-lived
      shuttles had lower growth rates than colonists and perennial stayers. Most groups
      grew best at intermediate bark pH. Interactions with other epiphytes had a small,
      often positive effect on growth. Neither differences in sensitivity of growth to
      habitat conditions nor differences in competitive abilities among species groups
      were found. Habitat conditions, however, influenced the production of
      sporophytes, but not of asexual diaspores. Presence of sporophytes negatively
      affected growth, whereas presence of asexual diaspores did not. Sexual species
      had to reach a certain colony size before starting to reproduce, whereas no such
      threshold existed for asexual reproduction. The results indicate that the
      epiphyte metacommunity is structured by two main trade-offs: dispersal distance
      vs. reproductive age, and dispersal distance vs. sensitivity to habitat quality.
      There seems to be a trade-off between growth and sexual reproduction, but not
      asexual. Trade-offs in species traits may be shaped by conflicting selection
      pressures imposed by habitat turnover and connectivity rather than by species
      interactions.

PMID- 19579036
TI  - Decreased renal uptake of (99m)Tc-DMSA in patients with tubular proteinuria.
AB  - Although technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) renal scans are
      widely used to evaluate renal tubular mass function, the mechanism by which renal
      uptake of DMSA occurs is still the subject of debate. Patients with various
      proximal tubular disorders show markedly decreased renal DMSA uptake, even when
      there is normal creatinine clearance. We measured the renal uptake of (99m)Tc
      DMSA 3 h after its injection in 13 patients with Dent disease or Lowe syndrome,
      both of which are typical proximal tubular disorders with defective megalin and
      cubilin-mediated endocytosis. Serial images of three patients were also obtained
      at 0.5, 1, 2 and 3 h post-injection. The correlations between renal uptake of
      (99m)Tc-DMSA and creatinine clearance and the degrees of acidemia and tubular
      proteinuria were then evaluated. The renal uptake of (99m)Tc-DMSA was markedly
      decreased in all patients, and the decreased uptake was detected in all serial
      images. In contrast, bladder radioactivity was higher than normal in all of the
      serial images when compared to renal radioactivity. Additionally, the uptake of
      (99m)Tc-DMSA was inversely proportional to the amount of urine beta(2)
      microglobulin. These results strongly suggest that DMSA is filtered in the
      glomeruli and subsequently undergoes megalin- and cubilin-mediated endocytosis in
      the proximal tubules.

PMID- 19579037
TI  - Social and psychological determinants of participation in internet-based cancer
      support groups.
AB  - PURPOSE: In this study, we identified the social and psychological
      characteristics of Danish cancer patients that determine use of the internet for
      support. MATERIALS AND METHODS: We invited 230 cancer patients taking part in a
      public rehabilitation program to participate in an internet module comprising
      training in the retrieval of cancer-related information from the internet and
      self-support groups. Persons who were motivated to join the internet groups (N =
      100; 47%) were compared with persons who chose not to participate (N = 111) on
      the basis of self-reported baseline questionnaire data. Nineteen persons either
      did not return the questionnaire or had missing values in confounding variables.
      RESULTS: Cancer patients who were motivated to participate in internet support
      groups belong to higher socioeconomic groups (based on household income and
      employment) compared to non-participants. We observed no difference between the
      two groups in quality of life or psychological well-being, while coping to some
      extent seemed related to participation in internet support groups. CONCLUSION:
      This study adds to the discussion on social inequality in internet use by cancer
      patients, showing that patients who are not inclined to use internet-based
      interventions are characterized by social position and employ more passive coping
      strategies.

PMID- 19579038
TI  - Landmark use by Clark's nutcrackers (Nucifraga columbiana): influence of
      disorientation and cue rotation on distance and direction estimates.
AB  - Many species have been shown to encode multiple sources of information to orient.
      To examine what kinds of information animals use to locate a goal we manipulated
      cue rotation, cue availability, and inertial orientation when the food-storing
      Clark's nutcracker (Nucifraga columbiana) was searching for a hidden goal in a
      circular arena. Three groups of birds were used, each with a different goal
      landmark distance. As the distance between the goal and the landmark increased,
      nutcrackers were less accurate in finding the correct direction to the goal than
      they were at estimating the distance (Experiment 1). To further examine what cues
      the birds were using to calculate direction, the featural cues within the
      environment were rotated by 90 degrees and the birds were either oriented when
      searching (Experiments 2 and 3) or disoriented (Experiment 3). In Experiment 4,
      all distinctive visual cues were removed (both internal and external to the
      environment), a novel point of entry was used and the birds were either oriented
      or disoriented. We found that disorienting the nutcrackers so that they could not
      use inertial cues did not influence the birds' total search error. The birds
      relied heavily but not completely on cues within the environment, as rotating
      available cues caused them to systematically shift their search behavior. In
      addition, the birds also relied to some extent on Earth-based cues. These results
      show the flexible nature of cue use by the Clark's nutcracker. Our study shows
      how multiple sources of spatial information may be important for extracting
      multiple bearings for navigation.

PMID- 19579039
TI  - Physical model for the width distribution of axons.
AB  - The distribution of widths of axons was recently investigated, and was found to
      have a distinct peak at an optimized value. The optimized axon width at the peak
      may arise from the conflicting demands of minimizing energy consumption and
      assuring signal transmission reliability. The distribution around this optimized
      value is found to have a distinct non-Gaussian shape, with an exponential "tail".
      We propose here a mechanical model whereby this distribution arises from the
      interplay between the elastic energy of the membrane surrounding the axon core,
      the osmotic pressure induced by the neurofilaments inside the axon bulk, and
      active processes that remodel the microtubules and neurofilaments inside the
      axon. The axon's radius of curvature can be determined by the cell's control of
      the osmotic pressure difference across the membrane, the membrane tension or by
      changing the composition of the different components of the membrane. We find
      that the osmotic pressure, determined by the neurofilaments, seems to be the
      dominant control parameter.

PMID- 19579040
TI  - Activating function of needle electrodes in anisotropic tissue.
AB  - We present an analytical solution for the electrical potential and activating
      function (AF) established by cylindrical needle electrodes in anisotropic tissue.
      We compare this activating function to (1) AF computed assuming line-source
      electrodes and (2) AF computed using a finite element program. The results show
      that when the fiber is two needle diameters away from the electrodes, the maximum
      of the AF for needle electrodes is 1.43-times larger than for line-source
      electrodes, which results in lower thresholds for stimulation and
      electroporation. Therefore, for fibers that are close to the stimulating
      electrodes, one would benefit from using the formula that accounts for the
      electrodes' geometry.

PMID- 19579041
TI  - Non-contact determination of parasympathetic activation induced by a full stomach
      using microwave radar.
AB  - In order to evaluate parasympathetic activation which causes driving errors,
      without placing any burden on the monitored individuals, we conducted a non
      contact parasympathetic activation monitoring through the back of a chair using a
      compact 24-GHz microwave-radar. We measured the high-frequency (HF, 0.15-0.4 Hz)
      power spectrum of heart rate variability (HRV) which reflects parasympathetic
      activation, induced by a full stomach. All participants had a large all-you-can
      eat meal with beverages for lunch within 20 min. Before and after the large meals
      for durations of 10 min, the non-contact measurement was conducted for seven
      healthy male volunteers (mean age: 23 +/- 1-year-old). In both non-contact
      (microwave radar) and contact (ECG as a reference) measurement, HF shows similar
      variations before and after large meal. Large meal significantly (p < 0.05)
      increased non-contact-derived HF from 1,026 +/- 510 to 1,893 +/- 613 ms(2) (922
      +/- 628 to 1,861 +/- 940 ms(2), p < 0.05). This technique allows parasympathetic
      activation monitoring for safety precautions.

PMID- 19579043
TI  - Marine two-headed sphingolipid-like compound rhizochalin inhibits EGF-induced
      transformation of JB6 P+ Cl41 cells.
AB  - Rhizochalin [(2R,3R,26R,27R)-2,27-diamino-3-hydroxy-26-[(2R,3R,4S,6R)-3,4,5
      trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy]octacosan-11-one], an
      antimicrobial and cytotoxic marine two-headed sphingolipid-like natural product,
      isolated from the sponge Rhizochalina incrustata, and some related compounds were
      studied as anticarcinogenic and proapoptotic agents. The corresponding effects
      were tested on the mouse skin epidermal JB6 P(+) Cl 41 cell line, its stable
      transfectants, THP-1, HeLa, and SNU-C4 human tumor cells using a variety of
      assessments, including cell viability (MTS), flow cytometry, anchorage
      independent soft agar, and luciferase assays. At 5-10 muM concentrations,
      rhizochalin was effective as an inhibitor of the malignant transformation of JB6
      P(+) Cl 41 cells or colony formation of human tumor cells, which exerted its
      action, at least in part, through the induction of p53-dependent apoptosis.
      Structure-activity relationship study showed aglycon of rhizochalin to be the
      most active while peracetylated aglycon was the least active among the compounds
      studied.

PMID- 19579044
TI  - Phosphorylation of native porcine olfactory binding proteins.
AB  - The identification of various isoforms of olfactory binding proteins is of major
      importance to elucidate their involvement in detection of pheromones and other
      odors. Here, we report the characterization of the phosphorylation of OBP
      (odorant binding protein) and Von Ebner's gland protein (VEG) from the pig, Sus
      scrofa. After labeling with specific antibodies raised against the three types of
      phosphorylation (Ser, Thr, Tyr), the phosphate-modified residues were mapped by
      using the beta-elimination followed by Michael addition of dithiothreitol (BEMAD)
      method. Eleven phosphorylation sites were localized in the pOBP sequence and nine
      sites in the VEG sequence. OBPs are secreted by Bowman's gland cells in the
      extracellular mucus lining the nasal cavity. After tracking the secretion pathway
      in the rough endoplasmic reticulum of these cells, we hypothesize that these
      proteins may be phosphorylated by ectokinases that remain to be characterized.
      The existence of such a regulatory mechanism theoretically increases the number
      of OBP variants, and it suggests a more specific role for OBPs in odorant coding
      than the one of odorant solubilizer and transporter.

PMID- 19579042
TI  - Involvement of lipids in dimethoate-induced inhibition of testosterone
      biosynthesis in rat interstitial cells.
AB  - The mechanism involved in the inhibition of testosterone (Te) biosynthesis after
      a sub-chronic exposure to low doses of dimethoate (D) was studied in rat
      interstitial cells (IC). Expression of COX-2 in IC isolated from D-treated rats
      increased by 44% over C data, while transcription of StAR decreased by approx.
      50% and the expression of this protein was diminished by approximately 40%.
      PGE(2) and PGF(2alpha) were increased by 61 and 78%, respectively. Te
      concentration decreased by 49% in IC homogenates. Concomitantly, plasma
      concentration of LH and FSH both increased. Araquidonate (ARA) and C(22) fatty
      acyl chains in phospholipids from IC mitochondrial fraction decreased by approx.
      30% after D treatment. Protein carbonyls, lipoperoxides and nitrite content
      increased while alpha-tocopherol and the antioxidant capacity of the soluble
      cellular fraction decreased significantly. Stimulation with h-CG 10 nM overnight
      failed to overcome the inhibition caused by D on both Te biosynthesis and 3beta-
      and 17beta-hydroxysteroid dehydrogenases. Decreased Te biosynthesis may be
      attributed to (1) inhibition of StAR protein activity due to the stimulation of
      COX-2 and the overproduction of PGF(2alpha), (2) decreased stimulatory effect of
      ARA on StAR with a subsequent reduction in the availability of CHO for the
      androgenic pathway, and/or (3) indirect inhibition of steroidogenic enzymes by a
      lower transcriptional rate caused by elevated PGF(2alpha). Rofecoxib
      administration prevents the deleterious effect(s) exerted by D.

PMID- 19579045
TI  - A two-component female-produced pheromone of the spider Pholcus beijingensis.
AB  - Chemical signaling plays an important role in spider sexual communication, yet
      the chemistry of spider sex pheromones remains poorly understood. Unlike insects
      and mammals, the identification of spider pheromones has seldom been attempted,
      and no multicomponent pheromones have been found. Empty webs of sexually
      receptive females of Pholcus beijingensis were more attractive to male
      conspecifics as compared to webs of sexually unreceptive females or to mature
      males. Coincidently, chemical analysis revealed that (E,E)-farnesyl acetate,
      diisobutyl phthalate, and hexadecyl acetate of the spider webs exhibited higher
      relative abundances in sexually receptive females than in sexually unreceptive
      females or males, indicative of possible pheromone components. Two-choice
      behavioral assays verified that the blend of (E,E)-farnesyl acetate and hexadecyl
      acetate (w/w: 2:1) attracted males at a dosage equivalent to the amounts of these
      compounds in one spider web, whereas neither compound alone aroused males. In
      addition, diisobutyl phthalate (a likely contaminant from contact with plastic)
      alone or in combination with either of the acetates did not evoke the males'
      attraction. The behavioral data suggest that (E,E)-farnesyl acetate and hexadecyl
      acetate comprise a two-component female-produced sex pheromone in P.
      beijingensis, the first multicomponent pheromone found in spiders.

PMID- 19579046
TI  - The influence of eastern North American autumnal migrant monarch butterflies
      (Danaus plexippus L.) on continuously breeding resident monarch populations in
      southern Florida.
AB  - In Florida, the eastern North American population of the monarch butterfly
      exhibits geographic variability in population structure and dynamics. This
      includes the occurrence of migrants throughout the peninsula during the autumnal
      migration, occasional overwintering clusters that form along the Gulf Coast,
      remigrants from Mexico that breed in north-central Florida during the spring, and
      what have been assumed to be year-round, resident breeding populations in
      southern Florida. The work reported here focused on two monarch populations west
      of Miami and addressed four questions: Are there permanent resident populations
      of monarchs in southern Florida? Do these breed continuously throughout the year?
      Do they receive northern monarchs moving south during the autumn migration? Do
      they receive overwintered monarchs returning via Cuba or the Yucatan during the
      spring remigration from the Mexican overwintering area? Monthly collections and
      counts of spermatophores in the bursa copulatrices of females established that a
      resident population of continuously breeding monarchs exists year-round in
      southern Florida. It was determined through cardenolide fingerprinting that most
      of the butterflies had bred on the local southern Florida milkweed species,
      Asclepias curassavica. During the autumn migration period, however, some monarchs
      had fed on the northern milkweed, Asclepias syriaca. It appears that instead of
      migrating to Mexico, these individuals travel south through peninsular Florida,
      break diapause, mate with and become incorporated into the resident breeding
      populations. None of the monarchs captured in spring had the A. syriaca
      cardenolide fingerprint, which is evidence against the southern Florida
      populations receiving overwintered remigrants from Cuba, Central America or
      Mexico.

PMID- 19579047
TI  - Violent patient behavior is associated with bodily pain and a high burden on
      informal caregivers.
AB  - BACKGROUND: There have been no studies of the relationship between violent
      behavior by older patients and the physical and mental health of caregivers.
      OBJECTIVE: To evaluate the influence of violent behavior in vulnerable elderly
      patients on bodily pain and caregiver burden in their informal caregivers.
      DESIGN: Cross-sectional study. SUBJECTS: One hundred thirty-seven patients aged >
      or =40 years old with limited activity and mobility in ten facilities providing
      home-care services in Japan. MEASUREMENTS: Degree of caregiver-perceived violent
      patient behavior and caregivers' bodily pain derived from a self-administered
      questionnaire, and caregiver burden assessed using scores from both the Burden
      Index of Caregivers and the Zarit Burden Interview. RESULTS: The mean age of the
      137 patients enrolled in this study was 80.9 years. Of these patients, 31.4% were
      men, and 34.3% had violent behavior. The mean caregiver age was 65.0 years, and
      29.2% were men. Caregivers who looked after violent patients experienced
      significantly higher odds of having bodily pain [AOR = 3.51; 95% confidence
      interval (CI): 1.81 to 6.85]. Caregivers of violent patients also reported
      significant caregiver burden as assessed by the Burden Index of Caregivers (beta
      coefficient = 4.92; 95% CI: 1.95 to 7.88) and the Zarit Burden Interview (beta
      coefficient = 5.81; 95% CI: 2.92 to 8.70). CONCLUSIONS: Violent behavior among
      older patients is associated with significant increases in both physical and
      psychological burden in their informal caregivers.

PMID- 19579048
TI  - Brief depression screening with the PHQ-2 associated with prognosis following
      percutaneous coronary intervention with paclitaxel-eluting stenting.
AB  - BACKGROUND: Depression is associated with adverse prognosis in cardiac patients,
      warranting the availability of brief and valid instruments to identify depressed
      patients in clinical practice. OBJECTIVES: We examined whether the two-item
      Patient Health Questionnaire (PHQ-2) was associated with adverse events in
      percutaneous coronary intervention (PCI) patients treated with paclitaxel-eluting
      stenting (using the continuous score and various cutoffs), overall and by gender.
      DESIGN: Prospective follow-up study. PARTICIPANTS: Consecutive PCI patients (n =
      796) seen at a university medical centre. MEASUREMENTS: PHQ-2 at baseline. The
      study endpoint was an adverse event, defined as a combination of death or non
      fatal myocardial infarction (MI) at follow-up (mean of 1.4 years). RESULTS: At
      follow-up, 47 patients had experienced an adverse event. Using the continuous
      score of the PHQ-2 and the recommended cutoff > or =3, depressive symptoms were
      not associated with adverse events (ps > 0.05). Using a cutoff > or =2,
      depressive symptoms were significantly associated with adverse events (HR: 1.89;
      95% CI: 1.06-3.35) and remained significant in adjusted analysis (HR: 1.90; 95%
      CI: 1.05-3.44). Depressive symptoms were associated with an increased risk of
      adverse events in men (HR: 2.69; 95% CI: 1.36-5.32) but not in women (HR: 0.76;
      95% CI: 0.24-2.43); these results remained in adjusted analysis. CONCLUSIONS:
      Depression screening with a two-item scale and a cutoff score of > or =2 was
      independently associated with adverse events at follow-up. The PHQ-2 is a brief
      and valid measure that can easily be used post PCI to identify patients at risk
      for adverse health outcomes.

PMID- 19579049
TI  - Association between hand-off patients and subject exam performance in medicine
      clerkship students.
AB  - BACKGROUND: Teaching hospitals increasingly rely on transfers of patient care to
      another physician (hand-offs) to comply with duty hour restrictions. Little is
      known about the impact of hand-offs on medical students. OBJECTIVE: To evaluate
      the impact of hand-offs on the types of patients students see and the association
      with their subsequent Medicine Subject Exam performance. DESIGN: Observational
      study over 1 year. PARTICIPANTS: Third-year medical students in an Inpatient
      Medicine Clerkship at five hospitals with night float systems. MEASUREMENTS: 
      PRIMARY OUTCOME: Medicine Subject Exam at the end of the clerkship; explanatory
      variables: number of fresh (without prior evaluation) and hand-off patients,
      diagnoses, subspecialty patients, and full evaluations performed during the
      clerkship, and United Stated Medical Licensing Examination (USMLE) Step I scores.
      MAIN RESULTS: Of the 2,288 patients followed by 89 students, 990 (43.3%) were
      hand-offs. In a linear regression model, the only variables significantly
      associated with students' Subject Exam percentile rankings were USMLE Step I
      scores (B = 0.26, P < 0.001) and the number of full evaluations completed on
      fresh patients (B =0.20, P = 0.048; model r (2) = 0.58). In other words, for each
      additional fresh patient evaluated, Subject Exam percentile rankings increased
      0.2 points. For students in the highest quartile of Subject Exam percentile
      rankings, only Step I scores showed a significant association (B = 0.22, P =
      0.002; r (2) = 0.5). For students in the lowest quartile, only fresh patient
      evaluations demonstrated a significant association (B = 0.27, P = 0.03; r (2) =
      0.34). CONCLUSIONS: Hand-offs constitute a substantial portion of students'
      patients and may have less educational value than "fresh" patients, especially
      for lower performing students.

PMID- 19579050
TI  - Prevalence of thrombophilias in patients presenting for bariatric surgery.
AB  - BACKGROUND: The rise in bariatric surgery has driven an increased number of
      complications from venous thromboembolism (VTE). Evidence supports obesity as an
      independent risk factor for VTE, but the specific derangements underlying the
      hypercoagulability of obesity are not well defined. To better characterize VTE
      risk for the purpose of tailoring prophylactic strategies, we developed a
      protocol for thrombophilia screening in patients presenting for bariatric surgery
      at our institution. METHODS: Between April 2004 and April 2006, 180 bariatric
      surgery candidates underwent serologic screening for inherited thrombophilias
      (Factor V-Leiden mutation, low Protein C activity, low Protein S activity, Free
      Protein S deficiency) and acquired thrombophilias (D-Dimer elevation, Fibrinogen
      elevation, elevation of coagulation factors VIII, IX, and XI, elevation of Lupus
      anticoagulants and homocysteine level, and Antithrombin III deficiency).
      Prevalence rate of each thrombophilia in the subject group was compared to the
      actual prevalence rate of the general population. RESULTS: Most plasma markers of
      both inherited and acquired thrombophilias were identified in higher than
      expected proportions, including D-Dimer elevation in 31%, Fibrinogen elevation in
      40%, Factor VIII elevation in 50%, Factor IX elevation in 64%, Factor XI
      elevation in 50%, and Lupus anticoagulant in 13%. CONCLUSIONS: Obesity is a well
      described demographic risk factor for VTE. In bariatric surgery candidates
      routinely screened for serologic markers, both inherited and acquired
      thrombophilias occurred more frequently than in the general population, and may
      therefore prove to be useful for individualized VTE risk assessment and
      prophylaxis.

PMID- 19579051
TI  - Transumbilical single-port laparoscopic adjustable gastric band placement with
      liver suture retractor.
AB  - BACKGROUND: The evolution of single-incision laparoscopic surgery (SILS) has no
      doubt been impacted by the decrease or elimination of incisions seen with natural
      orifice transluminal endoscopic surgery (NOTES). SILS upholds the principal
      advantages of minimal access surgery including shortened hospital stays, the
      potential for decreased postoperative pain, and cosmetically acceptable scars by
      reducing large or multiple incisions to a relatively small, single one. METHODS:
      As opposed to NOTES, SILS does not violate a natural orifice and so the potential
      for contamination is identical to that of laparoscopy. SILS also utilizes
      familiar technology regarding ports and instruments which make technical
      adaptation easier and costs remain essentially unchanged. Standard laparoscopic
      techniques for gastric band placement use up to six ports in various
      configurations to safely accomplish this procedure. We describe a 40-year-old
      female with a body mass index of 41 who underwent placement of a gastric band for
      weight reduction via a single incision. A novel liver retractor technique
      eliminated one of the typical incisions utilized in other described "single
      incision" techniques. RESULTS: The total number of trocars used at the sole,
      transumbilical incision was three. The operative time was 58 min. There were no
      intraoperative or postoperative complications. The patient was discharged on
      postoperative day 1. CONCLUSIONS: Single-incision transumbilical placement of
      gastric band is safe and technically feasible. Evolution of this technique with
      improved instrumentation will facilitate its adoption.

PMID- 19579052
TI  - Cigarette smoking and risk of prostate cancer among Singapore Chinese.
AB  - Prospective epidemiologic studies conducted in Western populations support an
      association between current smoking and aggressive subtypes of prostate cancer.
      In Singapore, where prostate-specific antigen is not used for population-wide
      screening, prostate cancer incidence has tripled within the past two decades.
      Using Cox regression methods, we examined the relationship between smoking and
      prostate cancer established between 1993 and 1998 in a cohort of 27,293 Singapore
      Chinese men. As of December 2006, 250 incident prostate cancer cases were
      diagnosed. In our cohort, 42.2% reported never smoking cigarettes, 15.7% quit
      over 5 years ago (long-term former), 5.7% quit within the past 5 years (recent
      former), and 36.4% were current smokers. From multivariable models, we observed
      no association with smoking status, age at starting to smoke, years smoked, or
      number of cigarettes per day. Among recent former and current smokers combined,
      we observed a small positive association for earlier age at starting to smoke
      that was somewhat stronger for nonadvanced disease (hazard ratio = 1.63, 95%
      confidence interval: 0.85, 3.12, for <15 years versus nonsmokers). Smoking was
      not a major risk factor for prostate cancer in our Singapore Chinese cohort, a
      traditionally low risk population with parallel increases in incidence and
      mortality.

PMID- 19579053
TI  - Multivariate analysis for characteristics of heat tolerance in horses in Brazil.
AB  - The environment in which the horse is reared affects its ability to maintain
      thermal balance which is in turn related to thermal characteristics and
      regulatory physiological mechanisms. In this study a multivariate analysis of
      physiological traits in relation to heat tolerance in horses was carried out in
      the Federal District, Brazil. The aim was to test the ability of these analyses
      to separate groups of animals and determine which physiological traits are most
      important in the adaptation to heat stress. Forty adult horses (4 to 13 years)
      were used, ten from each of four different genetic groups (English thoroughbred,
      Brazilian showjumper, crossbred and Breton). The traits examined included heart
      and breathing rate, rectal temperature as well as blood parameters. The data
      underwent multivariate statistical analysis including cluster, discriminate and
      canonical using Statistical Analysis System - SAS (R) procedures CLUSTER,
      STEPDISC, CANCORR and DISCRIM. The tree diagram showed clear distances between
      groups studied and canonical analysis was able to separate individuals in groups.
      The discriminate analysis identified the variables which were most important in
      separating these groups. The multivariate analysis was able to separate the
      animals into groups with RR, HR and RT being important in this separation.

PMID- 19579054
TI  - Influence of major genes for crested-head, frizzle-feather and naked-neck on body
      weights and growth patterns of indigenous chickens reared intensively in Kenya.
AB  - The influence of major genes for crested-head (Cr), frizzle-feather (Fr) and
      naked-neck (Na) on body weights and growth patterns of indigenous chickens reared
      intensively was investigated and compared with normal-feather (na) gene. Birds
      were individually weighed at hatch and every two weeks up to 30 weeks of age.
      Growth patterns were modelled using the Gompertz-Laird function. The genes
      influenced body weights and growth patterns at various ages. The Cr gene had
      significant (P < 0.05) negative effects on body weights (between 52.2 g and 112.3
      g) from 18 weeks onwards and low absolute growth rate from 10 to 22 weeks than
      na, but higher initial specific growth and maturation rates than the Na gene. The
      Fr gene had significant negative effects on body weights (between 28.2 g and 75.1
      g) from 8 to 16 weeks than na, but a higher relative growth rate than Cr from 12
      to 16 weeks. The Na gene had significant negative effects on body weights
      (between 24.7 g and 134.6 g) from 8 weeks onwards than na. It was concluded that
      Frfr and Nana genotypes are not ideal for cool environments in Kenya and
      indigenous chicken genotypes have varied growth potentials and patterns that can
      be improved to increase production.

PMID- 19579055
TI  - An evaluation of the integration of standards and guidelines in community
      pharmacy practices.
AB  - OBJECTIVE: To explore the usefulness and implementation of practice standards in
      community pharmacy practice regarding contemporary core services. SETTING:
      Community pharmacies in South East Queensland, Australia. METHOD: During August
      and September 2006 semi-structured interviews with community pharmacists explored
      practice processes and procedures and the utilisation of endorsed standards and
      guidelines. Thematic content analysis of the interviews, inductive analysis and
      continual comparison of categories and concepts enabled common and distinct
      themes to be clarified. MAIN OUTCOME MEASURE: Usefulness and integration of
      practice standards in the provision of core pharmacy services, utilisation of
      support staff, record keeping and overall risk management processes in community
      pharmacy. RESULTS: Seventeen community pharmacists participated, representing a
      wide range of demographics, experience and pharmacy types. Staff utilisation and
      record keeping practices were analysed as well as two core services, namely: (1)
      the supply of over-the-counter medicines, and (2) the dispensing of
      prescriptions. The procedures followed concerning the supply of over-the-counter
      medicines varied. The majority of participants did not regard this as a
      pharmacist's immediate role, but rather relied on support staff to identify when
      the supply required a pharmacist's intervention. Whilst all participants involved
      dispensary assistants in the dispensing process, the delegation of procedures
      differed. Most participants did not clearly differentiate between pharmacists'
      and dispensary assistants' activities. Dispensing processes and the involvement
      of pharmacists in the provision of patient advice varied. Pharmacist intervention
      record keeping was uncommon and records of 'near misses' were not routinely kept
      by any of the participants. CONCLUSION: A lack of integration of practice
      standards indicated a need to review the standards for relevance. Additionally,
      pharmacists need to re-evaluate workflow models and the delegation of tasks in
      the light of new roles and responsibilities.

PMID- 19579056
TI  - Mutational analysis of Arabidopsis PP2CA2 involved in abscisic acid signal
      transduction.
AB  - The homozygous T-DNA mutant of the PP2CA2 gene in Arabidopsis thaliana was
      identified at DNA and RNA levels. The semi-quantitative RT-PCR analysis showed
      expression of PP2CA2 was induced by NaCl and ABA. When grown in presence of
      increasing concentration of exogenous ABA the pp2ca2 mutant showed a significant
      loss of ABA sensitivity in terms of seed germination, efficiency of post
      germination growth and root growth. In presence of all ABA and NaCl
      concentrations tested the germination percentage of wild-type seeds was lower
      than that of mutant ppca2 seeds. Furthermore, in the presence of exogenous ABA,
      the pp2ca2 seeds showed higher germination percentages than wild-type at
      different stages of development and the pp2ca2 seedlings showed a reduced
      inhibition of root growth compared with wild-type plants. The above results
      indicated that the pp2ca2 was an ABA-hyposensitive mutant.

PMID- 19579059
TI  - Bax inhibitor-1 mediates apoptosis-resistance in human nasopharyngeal carcinoma
      cells.
AB  - Bax inhibitor-1 (BI-1), a newly identified apoptosis inhibitor, has recently been
      found to be overexpressed in several human carcinomas and its specific down
      regulation by RNA interference (RNAi) could lead to cell death. The purpose of
      this study is to investigate the role of BI-1 in apoptosis-resistance and the
      underlying mechanisms in human nasopharyngeal carcinoma (NPC) cells. Our results
      showed that BI-1 was expressed in two different human NPC cell lines, CNE-2Z and
      CNE-1, and specific inhibition of BI-1 expression by siRNA caused a significant
      increase in spontaneous apoptosis in both cell lines. Mechanistically, we
      demonstrated that down-regulation of BI-1 protein expression decreased the ratio
      of Bcl-X(L)/Bcl-2 with Bax protein as determined by Western blot and increased
      the activity of caspase-3 by colorimetric analysis, thus leading to the
      activation of the associated cell death pathways. Taken together, these results
      have provided evidence that BI-1 could serve as an important molecular target
      gene for the development of new therapeutic strategy against human NPCs.

PMID- 19579058
TI  - Primary large cell neuroendocrine carcinoma of the kidney.
AB  - We report a case of a 56-year-old male with a primary large cell neuroendocrine
      renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that
      measured 145 x 125 x 100 mm. Histologically, the tumor consisted of large cells
      with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were
      irregular, some of them with finely or coarsely granular chromatin, others with
      vesicular chromatin and prominent nucleoli. The tumor cells showed multiple
      mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were
      arranged in solid sheets; however, the predominant pattern was solid-alveolar,
      trabecular and cribriform. Large areas of tumor necrosis were found.
      Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and
      CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally.
      Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin
      CAM5.2, cytokeratin 34betaE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin
      20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and
      insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney
      is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this
      type have been reported to date.

PMID- 19579057
TI  - Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions
      with components of the actin and intermediate filament cytoskeleton.
AB  - Thiolutin is a dithiole synthesized by Streptomyces sp. that inhibits endothelial
      cell adhesion and tumor growth. We show here that thiolutin potently inhibits
      developmental angiogenesis in zebrafish and vascular outgrowth from tissue
      explants in 3D cultures. Thiolutin is a potent and selective inhibitor of
      endothelial cell adhesion accompanied by rapid induction of HSPB1 (Hsp27)
      phosphorylation. The inhibitory effects of thiolutin on endothelial cell adhesion
      are transient, potentially due to a compensatory increase in Hsp27 protein
      levels. Accordingly, heat shock induction of Hsp27 limits the anti-adhesive
      activity of thiolutin. Thiolutin treatment results in loss of actin stress
      fibers, increased cortical actin as cells retract, and decreased cellular F
      actin. Mass spectrometric analysis of Hsp27 binding partners following
      immunoaffinity purification identified several regulatory components of the actin
      cytoskeleton that associate with Hsp27 in a thiolutin-sensitive manner including
      several components of the Arp2/3 complex. Among these, ArpC1a is a direct binding
      partner of Hsp27. Thiolutin treatment induces peripheral localization of
      phosphorylated Hsp27 and Arp2/3. Hsp27 also associates with the intermediate
      filament components vimentin and nestin. Thiolutin treatment specifically ablates
      Hsp27 interaction with nestin and collapses nestin filaments. These results
      provide new mechanistic insights into regulation of cell adhesion and
      cytoskeletal dynamics by Hsp27.

PMID- 19579061
TI  - Formulation and characterization of glass-ceramics based on Na2Ca2Si3O9
      Ca5(PO4)3F-Mg2SiO4-system in relation to their biological activity.
AB  - Glasses having a chemical composition based on combeite [Na(2)Ca(2)Si(3)O(9)]
      fluoroapatite [Ca(5)(PO(4))(3)F] and forsterite [Mg(2)SiO(4)] system were
      crystallized through controlled heat-treatment. Two forms of sodium calcium
      silicate e.g. combeite Na(2)Ca(2)Si(3)O(9) and pectolite Na(2)CaSi(3)O(8), were
      formed together with diopside (CaMgSi(2)O(6)) and monticellite (CaMgSiO(4)) in
      addition to fluoroapatite (Ca(5)(PO(4))(3)F) phases by thermal treatment of the
      glasses. Selected glass-ceramics were exposed to a simulated body fluid solution
      (SBF) which is close to human plasma for 3 weeks. Energy dispersive X-ray
      analysis (EDX) and inductive coupled plasma (ICP) analysis confirmed the
      formation of an apatite layer which indicate bioactivity in the all crystallized
      sample. A decreasing of surface bioactivity with increasing
      Mg(2)SiO(4)/Na(2)Ca(2)Si(3)O(9) replacement was observed as indicated by the
      decrease in the amount of apatite layer on the surface of the crystallized
      specimens. The Vicker's microhardness of the studied glass-ceramic materials are
      between 5,047 and 6,781 MPa.

PMID- 19579060
TI  - Phosphorylation of translation factors in response to anoxia in turtles,
      Trachemys scripta elegans: role of the AMP-activated protein kinase and target of
      rapamycin signalling pathways.
AB  - Long-term survival of oxygen deprivation by animals with well-developed anoxia
      tolerance depends on multiple biochemical adaptations including strong metabolic
      rate depression. We investigated whether the AMP-activated protein kinase (AMPK)
      could play a regulatory role in the suppression of protein synthesis that occurs
      when turtles experience anoxic conditions. AMPK activity and the phosphorylation
      state of ribosomal translation factors were measured in liver, heart, red muscle
      and white muscle of red-eared slider turtles (Trachemys scripta elegans)
      subjected to 20 h of anoxic submergence. AMPK activity increased twofold in white
      muscle of anoxic turtles compared with aerobic controls but remained unchanged in
      liver and red muscle, whereas in heart AMPK activity decreased by 40%.
      Immunoblotting with phospho-specific antibodies revealed that eukaryotic
      elongation factor-2 phosphorylation at the inactivating Thr56 site increased six-
      and eightfold in red and white muscles from anoxic animals, respectively, but was
      unchanged in liver and heart. The phosphorylation state of the activating Thr389
      site of p70 ribosomal protein S6 kinase was reduced under anoxia in red muscle
      and heart but was unaffected in liver and white muscle. Exposure to anoxia
      decreased 40S ribosomal protein S6 phosphorylation in heart and promoted
      eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) dephosphorylation in
      red muscle, but surprisingly increased 4E-BP1 phosphorylation in white muscle.
      The changes in phosphorylation state of translation factors suggest that organ
      specific patterns of signalling and response are involved in achieving the anoxia
      induced suppression of protein synthesis in turtles.

PMID- 19579062
TI  - Mechanical properties of three different compositions of calcium phosphate
      bioceramic following immersion in Ringer's solution and distilled water.
AB  - Dissolution tests were carried out to compare the mechanical properties of
      calcium phosphate based bioceramics with different compositions, before and after
      ageing for various time periods in Ringer's solution (pH 7.2) or distilled water
      (pH 7.2 and 4.0) at 37 degrees C. The results indicate that the sample
      composition seems to have more of an effect on the mechanical properties than
      does the storage environment. No obvious decrease in mechanical properties was
      found after samples had been aged in the various solutions during the different
      time periods. This indicates that these samples could be of significant clinical
      interest as their good structural properties were retained.

PMID- 19579063
TI  - Sequence analysis of the prion protein gene in Mongolian gazelles  (Procapra
      gutturosa).
AB  - Prion diseases are a group of human and animal neurodegenerative conditions,
      which are caused by the deposition of an abnormal isoform prion protein (PrPSc)
      encoded by a single copy prion protein gene (Prnp). In sheep, genetic variations
      of Prnp were found to be associated with the incubation period, susceptibility,
      and species barrier to the scrapie disease. We investigated the sequence and
      polymorphisms of the prion protein gene of Mongolian gazelles (gPrnp). gPrnp gene
      sequence analysis of blood samples from 26 Mongolian gazelles showed high
      identity within species. The gPrnp gene was closely related to the Prnp genes of
      Thomson's gazelle, blackbuck, and cattle with 100, 100, and 98.5% identity,
      respectively, whereas the gPrnp gene with a deletion was closely related to the
      Prnp genes of wildebeest, Western roe deer, and sheep with 99.3, 99.3, and 98.9%
      identity, respectively. Polymorphisms of the open reading frame of Prnp as amino
      acid substitutions were detected at codons 119(N --> S), 143(S --> G) or 160(Y -
      > H), 172(V --> A), 182(N --> S) and 221(V --> A). There was also deletion of one
      octapeptide repeat at the N-terminal octapeptide repeat region. The polymorphisms
      of gPrnp will assist the study of prion disease pathogenesis, resistance, and
      cross species transmission.

PMID- 19579064
TI  - Mitochondrial DNA variation in the CoxI-CoxII intergenic region among Turkish and
      Iranian honey bees (Apis mellifera L.).

PMID- 19579065
TI  - Unhealthy partnerships: the tobacco industry and African American and Latino
      labor organizations.
AB  - The tobacco industry in the 1980s began to form relationships with outside groups
      for assistance on key policy issues due to its own poor credibility in the policy
      arena. This strategy allowed the industry to advance its own interests while
      seeming to match the agendas of very different organizations. Between 1988 and
      1998, the tobacco industry developed coalitions with the A. Philip Randolph
      Institute (APRI), representing African American trade unionists, and the Labor
      Coalition on Latin American Advancement (LCLAA), representing Latino trade
      unionists. APRI and LCLAA each adopted resolutions supporting industry positions
      on smokefree worksites and excise taxes, issues on which they had not previously
      taken positions, and promoted these positions to their members, political leaders
      and the public. They also supported the industry's youth programs. This research
      relied upon a review of background literature and document searches through the
      Legacy Tobacco Documents Library and Tobacco Documents Online to examine the
      development of the excise tax coalition. The tobacco industry built support with
      APRI and LCLAA by framing policy positions in line with the organizations'
      interests, creating institutional arrangements that circumvented direct funding
      from the industry, and enhancing the industry's ability to influence excise tax
      debates indirectly. Although tobacco control advocates do not have the financial
      resources of the tobacco industry at their disposal, they can learn from tobacco
      industry techniques as they seek to build coalitions with people of color in the
      labor movement. Tobacco control advocates can both counter tobacco industry issue
      frames and also align their interests with those of working people of color by
      working on other issues of interest to this population, including health care and
      worker health and safety.

PMID- 19579067
TI  - Protection against in vivo focal myocardial ischemia/reperfusion injury-induced
      arrhythmias and apoptosis by hesperidin.
AB  - Among the heart diseases, ischemia and reperfusion (I/R) induced arrhythmias
      contribute to episodes of sudden death. Cardiac arrhythmias during ischemia
      reperfusion are believed to be related to oxidative stress. Therefore, the aim of
      this study was to examine whether treatment with hesperidin alleviates
      arrhythmias and infarct size in experimentally-induced myocardial I/R injury
      using an in vivo rat model. In this study haemodynamics parameters, markers of
      inflammation, biomarkers of oxidative stress and tissue nitrite level and infarct
      size of the heart were estimated in various groups. I/R showed a significant
      decrease in tissue nitrite and antioxidant level and significant increase in
      arrhythmias, inflammation and myocardial cell apoptosis. Treatment with
      hesperidin showed a significant increase in tissue nitrite, antioxidant level and
      reduction in inflammation, arrhythmias and apoptosis. In conclusion, the
      protecting effect of hesperidin in I/R induced arrhythmias is due to reduction in
      inflammation and oxidative stress.

PMID- 19579066
TI  - Patient attitudinal and behavioral factors associated with warfarin non-adherence
      at outpatient anticoagulation clinics.
AB  - BACKGROUND: Warfarin is an anticoagulant effective in preventing stroke, but it
      has a narrow therapeutic range requiring optimal adherence to achieve the most
      favorable effects. PURPOSE: The goal of this study was to examine specific
      patient factors that might help explain warfarin non-adherence at outpatient
      anticoagulation clinics. METHOD: In a prospective cohort study of 156 adults, we
      utilized logistic regression analyses to examine the relationship between the
      five Treatment Prognostics scales from the Millon Behavioral Medicine Diagnostic
      (MBMD), as well as three additional MBMD scales (Depression, Future Pessimism,
      and Social Isolation), and daily warfarin non-adherence assessed using electronic
      medication event monitoring systems caps over a median of 139 days. RESULTS: Four
      of the five Treatment Prognostic scales and greater social isolation were
      associated with warfarin non-adherence. When controlling for pertinent
      demographic and medical variables, the Information Discomfort scale remained
      significantly associated with warfarin non-adherence over time. CONCLUSION:
      Although several factors were related to warfarin non-adherence, patients
      reporting a lack of receptivity to details regarding their medical illness seemed
      most at risk for warfarin non-adherence. This information might aid in the
      development of interventions to enhance warfarin adherence and perhaps reduce
      adverse medical events.

PMID- 19579068
TI  - Public health requirements for rapid progress in global health.
AB  - Effective public health interventions can save hundreds of millions of lives in
      developing countries, as well as create broad social and economic benefits.
      Unfortunately, public health approaches and solutions applied in developed
      countries are often assumed to be inappropriate or unattainable in developing
      countries. This has sometimes forestalled effective interventions in parts of the
      world where they are most needed, despite conditions that now facilitate lasting
      solutions to both long-standing and emerging global public health problems. Core
      public health functions are similar regardless of a country's income level.
      Although some resource-intensive approaches from industrialised nations are
      inappropriate in less developed countries, many basic public health measures
      achieved decades ago in developed countries are urgently needed, highly
      appropriate, extremely cost-effective and eminently attainable in developing
      countries today. About half of the disease burden in low and middle-income
      countries is now from non-communicable diseases, but non-communicable disease
      epidemics that will otherwise increase rapidly in the developing world can be
      avoided or reversed. Progress of public health in developing countries is
      possible, but will require sufficient funding and human resources; improved
      physical plant and information systems; effective programme implementation and
      regulatory capacity; and, most importantly, political will at the highest levels
      of government.

PMID- 19579070
TI  - Repetitive 50 Hz pulsed electromagnetic field ameliorates the diabetes-induced
      impairments in the relaxation response of rat thoracic aorta rings.
AB  - PURPOSE: To evaluate the characteristic features of mechanical responses and the
      membrane potential changes induced by repetitive pulsed electromagnetic field
      (PEMF, 50 Hz, 5 mT) in thoracic aorta rings obtained from streptozotocin-induced
      diabetic and healthy control rats to determine if PEMF could ameliorate problems
      associated with diabetes. METHODS: Sixty male Wistar rats weighing 250-290 g were
      randomly divided into two experimental groups, each containing 30 animals.
      Streptozotocin was given via tail vein to produce diabetes mellitus (DM) in the
      first group rats. The second group rats were treated only with % 0.9 saline and
      considered as non-DM group. Both groups were also divided into two subgroups as
      DM + PEMF, DM + sham, PEMF and sham, each containing 15 animals. Although the DM
      + PEMF and PEMF groups were treated, the DM + sham and sham groups were not
      treated with PEMF. The PEMF treatment occurred four times daily for 30 min at 15
      min intervals repeated daily for 30 days. Thoracic aorta rings from both DM and
      non-DM rats exposed to PEMF were evaluated for contraction and relaxation
      responses and membrane potential changes in the presence or absence of chemical
      agents that were selected to test various modes of action. RESULTS: Relaxation
      response of thoracic aorta rings was significantly reduced in DM than non-DM
      group. PEMF treatment significantly increased the relaxation response of the
      diabetic rings to acetylcholine, and reduced the concentration response to
      phenylephrine. Resting membrane potential was significantly higher in DM than in
      non-DM group. Inhibitors of nitric oxide (NO), both nitro-L-arginine (L-NO-ARG)
      and L-NO-ARG + indometacin combination, produced a significant transient
      hyperpolarisation in all groups. Inhibitors of potassium channel activity,
      charybdotoxin or apamine, produced a membrane depolarisation. However, PEMF did
      not induce any significant effect on the membrane potential in DM group.
      CONCLUSIONS: Diabetes reduced the relaxation response of thoracic aorta rings. It
      also affected the membrane potentials of the rings. Treatment with PEMF
      ameliorated the diabetes-induced impairments in the relaxation response of these
      rings.

PMID- 19579071
TI  - Conversations on psoriasis--what patients want and what physicians can provide: a
      qualitative look at patient and physician expectations.
AB  - BACKGROUND: The role of the patient-physician relationship is a key issue in the
      management of lifelong, chronic conditions such as psoriasis, with each side
      bringing different perspectives. OBJECTIVE: To explore areas of congruence and
      disconnection in the relationship between psoriasis patients and dermatologists,
      with a focus on communication issues. METHODS: Three discussion group sessions
      were held in four centers across the United States with dermatologists, patients,
      and a follow-up of the dermatologists after watching the patient discussion.
      RESULTS: Patients want more information on psoriasis, fast treatments, clear
      expectations from the onset of therapy, and recognition of the emotional burden.
      Dermatologists found that patients do not receive or internalize adequate
      information and need further explanation of treatment regimens to increase
      compliance and patient satisfaction. LIMITATIONS: This was a qualitative study
      assessing the range of responses and was not a quantitative study designed to
      test specific hypotheses. The study may not be informative about the experiences
      of people with psoriasis not actively seeing a physician. CONCLUSIONS: Encounters
      between physicians and psoriasis patients can be enhanced by providing
      information on what psoriasis is, choosing fast-acting treatments that patients
      are willing to use, and providing written materials about the disease and
      treatment plan.

PMID- 19579069
TI  - Response of heterogeneous ribonuclear proteins (hnRNP) to ionising radiation and
      their involvement in DNA damage repair.
AB  - PURPOSE: To determine the relationship between heterogeneous nuclear
      ribonucleoproteins (hnRNP) and DNA repair, particularly in response to ionising
      radiation (IR). MATERIALS AND METHODS: The literature was examined for papers
      related to the topics of hnRNP, IR and DNA repair. RESULTS: HnRNP orchestrate the
      processing of mRNA to which they are bound in response to IR. HnRNP A18, B1,
      C1/C2 and K interact with important proteins from DNA Damage Response (DDR)
      pathways, binding DNA-dependent protein kinase (DNA-PK), the Ku antigen (Ku) and
      tumour suppressor protein 53 (p53) respectively. Notably, irregularities in the
      expression of hnRNP A18, B1, K, P2 and L have been linked to cancer and
      radiosensitivity. Sixteen different hnRNP proteins have been reported to show
      either mRNA transcript or protein quantity changes following IR. Various protein
      modifications of hnRNP in response to IR have also been noted: hnRNP A18, C1/C2
      and K are phosphorylated; hnRNP C1/C2 is a target of apoptotic proteases; and
      hnRNP K degradation is controlled by murine double minute ubiquitin ligase
      (MDM2). Evidence points to a role for hnRNP A1, A18, A2/B1, C1/C2, K and P2 in
      regulating double-stranded break (DSB) repair pathways by promoting either
      homologous recombination (HR) or non-homologous end rejoining (NHEJ) repair
      pathways following IR. CONCLUSIONS: HnRNP proteins play a pivotal role in
      coordinating repair pathways following exposure to IR, through protein-protein
      interactions and transcript regulation of key repair and stress response mRNA. In
      particular, several hnRNP proteins are critical in coordinating the choice of HR
      or NHEJ to repair DSB caused by IR.

PMID- 19579072
TI  - Longitudinal myelitis associated with yellow fever vaccination.
AB  - Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever
      vaccine-associated neurotropic disease. This terminology includes postvaccinal
      encephalitis, acute disseminated encephalomyelitis, and Guillain-Barre syndrome.
      The objective of this communication is to report a patient who received a YF
      vaccine in Argentina and subsequently developed longitudinal myelitis with a
      symptom that had previously gone unreported in the literature. A 56-year-old man
      began with progressive paraparesia, urinary retention, and constipation 48 h
      previous to admission. The patient received YF vaccine 45 days prior to the onset
      of the symptoms. There was no history of other immunization or relevant
      condition. MR of the spine showed longitudinal intramedullary hyperintense signal
      (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM
      vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests
      for other flavivirus were negative. A diagnosis of longitudinal myelitis without
      encephalitis associated with YF vaccine was performed and symptoms improved 5
      days later. This is the first report dealing with longitudinal myelitis as a
      serious adverse event associated with YF vaccination in which confirmation of the
      presence of antibodies in CSF was found. To date, it is also the first report
      with serological confirmation in Argentina and in South America. We consider that
      the present investigation will raise awareness in the region in the reporting of
      adverse events related to YF vaccine and improve our knowledge of adverse
      reactions to the vaccine.

PMID- 19579073
TI  - Clinical and laboratory characterization of a large cohort of patients with
      Castleman disease retrospectively collected from a single center.
AB  - The clinical, pathological treatment, and prognostic data of 55 patients with
      Castleman disease (CD) were collected retrospectively from a single medical
      center. Thirty-four cases were classified as uni-centric; the remaining 21 cases
      were diagnosed as multi-centric CD. Regarding pathological classification, 38
      cases were hyaline vascular type, account for 69.1% of all patients. Nine cases
      were diagnosed as plasmacytic type and eight cases as mixed cellularity type.
      Several prominent clinical complications were noted in this group of patients
      with CD: the skin, internal organs, and hematopoietic system were involved
      individually or concurrently. Clinical complications were distinct between
      different clinical and pathological subtypes of CD. The unique clinical and
      laboratory features of patients with paraneoplastic pemphigus suggests this
      diagnosis should be characterized as an independent disease entity. The presence
      of clinical complications is an independent prognostic factor in all patients
      with CD. More effective initial therapy should be considered in patients with CD
      with complications to improve the overall survival.

PMID- 19579074
TI  - Long term outcome of localized aggressive non-Hodgkin lymphoma treated with a
      short weekly chemotherapy regimen (doxorubicin, cyclophosphamide, bleomycin,
      vincristine, and prednisone) and involved field radiotherapy: result of a Gruppo
      Italiano Multiregionale per lo Studio dei Linfomi e Leucenie (GIMURELL) study.
AB  - Recently, management of limited stage diffuse large cell lymphoma (DLCL) is
      trending toward a low intensity chemotherapy approach. Since 1993 we have used a
      brief weekly (6 weeks) chemotherapy scheme (Doxorubicin, Cyclophosphamide,
      Bleomycin, Vincristine, and Prednisone = ACOP-B) followed by involved field
      radiotherapy in 207 consecutive patients with well defined localized DLCL without
      age limit (median 57 years, range 18-85). Treatment was completed as designed in
      183 of 207 patients (88%). One hundred and ninety-nine patients (96%) achieved
      complete remission. At a median follow-up of 66 months 170 patients are alive
      (82%), 168 of them free of disease. Twenty-nine patients experienced relapse
      after achieving a complete remission. Kaplan-Meier, risk of relapse was 24% after
      13 years. Thirty (14.5%) patients have died, 14 (6.8%) due to lymphoma
      progression, one due to regimen toxicity and 15 (7.2%) from other causes while
      remaining in complete remission. The probability of overall survival and event
      free survival at 13 years was 78% (95% CI 70-87%) and 63% (95% CI 50-75),
      respectively. Crude rate of secondary malignancy was 5.26 /1000 person-years. The
      ACOP-B regimen plus involved field radiotherapy is well tolerated both short and
      long term and is an effective chemotherapy scheme for very well defined limited
      stage aggressive non-Hodgkin lymphomas in all age categories.

PMID- 19579075
TI  - Genetic rearrangement MLL/AF4 is most frequent in children with acute
      lymphoblastic leukemias in Mexico City.
AB  - One of the highest incidences of acute lymphoblastic leukemia (ALL) in the world
      has been reported in Mexico City. In the current study (26 cases), the
      frequencies of the most frequent genetic rearrangements TEL-AML1, MLL/AF4, BCR
      ABL (major and minor) in ALL in children from Mexico City were determined. For
      the ALL, the frequency of MLL/AF4 was 65.4%, for TEL-AML1 and that of BCR/ABL was
      3.8%. Only 6 of the 17 children with the MLL/AF4 rearrangement were less than 26
      months old. The frequency reported for MLL/AF4 in Mexican children with ALL is
      one of the highest worldwide. These findings could potentially explain the higher
      frequency of ALL with poor prognosis for children in Mexico City.

PMID- 19579076
TI  - Clinical profile and home management of sickle cell-related pain: the Enugu
      (Nigeria) experience.
AB  - OBJECTIVE: To document the pattern of and ability of sickle cell anemic patients
      to manage painful crises at home. SUBJECT AND METHODS: Confirmed HbSS patients or
      caregivers attending the University of Nigeria Teaching Hospital (UNTH), Enugu,
      Nigeria, were interviewed, using a questionnaire, on their last painful episode.
      RESULTS: The limbs were involved in all ages, but involvement of the joints,
      ribs, and spine was uncommon in patients under 5 years old. Pain started between
      6 pm and 12 midnight in 33.3%. Analgesics with or without massage or hydration
      was mostly used at home. 29% of subjects required hospitalization. CONCLUSION:
      Patients need better access to more potent analgesics to reduce the burden on the
      health system.

PMID- 19579077
TI  - The benefit of ATG in immunosuppressive therapy of children with moderate
      aplastic anemia.
AB  - BACKGROUND: Previous studies specifically focused on the immunosuppressive
      therapy (IST) of children with moderate aplastic anemia (MAA) are rare. The aim
      of this study was to evaluate the advantage of using antithymocyte globulin (ATG)
      in the IST and its outcome of children with MAA. METHODS: Forty-two children
      diagnosed with moderate aplastic anemia from 1993 to 2006 were retrospectively
      reviewed. Eighteen patients treated with ATG, cyclosporin A (CSA), and androgen
      are defined as the ATG group, the other 24 patients treated with CSA and androgen
      are defined as the non-ATG group. Survival and hematological response of the two
      groups were studied. RESULTS: Response rate and transfusion-independent survival
      of the ATG group were both significantly higher than those of the non-ATG group
      (83.33 vs. 41.7%, p = .006; and 83.33 vs. 50%, p = .043, respectively). Compared
      with non-ATG group, fewer patients in ATG group progress to severe aplastic
      anemia (p = .03). CONCLUSION: Immunosuppressive therapy including ATG benefits
      children with moderate aplastic anemia.

PMID- 19579078
TI  - Rhabdomyosarcoma of the extremities: a focus on tumors arising in the hand and
      foot.
AB  - BACKGROUND: Extremities are peculiar sites of origin for rhabdomyosarcomas (RMS)
      and are usually associated with an unfavorable outcome. METHODS: The authors
      reviewed the clinical data on 60 patients <21 years old with limb RMS treated at
      the Pediatric Oncology Unit of the Istituto Nazionale Tumori of Milan, in Italy,
      over a 30-year period. Twelve patients had tumors arising in the hand and foot.
      RESULTS: Complete tumor resection was achieved in 21 patients (but in only 1 case
      of hand/foot RMS); all patients received chemotherapy and 43 also had
      radiotherapy. The alveolar subtype was identified in 62% of cases. Half of the
      hand/foot cases had metastatic disease at onset. Overall survival at 5 years was
      33% among the hand/foot cases and 56% for the others. Most of the relapsing cases
      had distant metastases. CONCLUSIONS: A particularly poor survival was observed
      for RMS of the hand/foot due its marked tendency to spread. Surgical resection is
      particularly difficult in such cases and a multimodality treatment approach seems
      crucial to improving their outcome.

PMID- 19579079
TI  - Incidence of primary central nervous system tumors among children in Belgrade
      (Serbia), 1991-2004.
AB  - The aim of this survey was to estimate the incidence of primary CNS tumors among
      children aged 0-14 in Belgrade during the period 1991-2004. Incidence rates were
      age-adjusted according to the world standard population. The average age-adjusted
      incidence rates were 3.4/100,000 for boys, 2.4/100,000 for girls, and 2.9/100,000
      for both genders. There was a nonsignificant tendency toward increased CNS tumor
      incidence (y = 2.547 + 0.052 x, p = .549). The age-specific incidence rates were
      3.0/100,000 (0-4 years), 2.2/100,000 (5-9 years), and 3.8/100,000 (10-14 years).
      Among the population aged between 0 and 14, the cumulative probability of
      acquiring primary CNS tumors was 1 per 1961 for boys and 1 per 2778 for girls.
      Astrocytoma was the most common pathohistological type of primary CNS tumors
      accounting for 41.5% of cases.

PMID- 19579080
TI  - Panel reactive antibody in thalassemic serum inhibits proliferation and
      differentiation of cord blood CD34+ cells in vitro.
AB  - Thalassemic children are at a high risk of graft rejection in cord blood
      transplantation. To investigate this possible mechanism, the authors evaluated
      the effect of panel reactive antibody on the growth of CD34(+) cells in vitro. On
      semisolid medium, CD34(+) cells derived from cord blood were incubated with
      thalassemic serum, and colony-forming units were counted after 10 days of
      culture. After incubation with serum-specific panel reactive antibody, profound
      decreases were found in the numbers of CFU-GM, CFU-GEMM and BFU-E compared with
      controls. The results indicated that serum-specific panel reactive antibody might
      have an apparent inhibition effect on proliferation and differentiation of cord
      blood CD34(+) cells.

PMID- 19579081
TI  - Allogeneic stem cell transplantation for myelodysplastic syndromes in children: a
      report from the Spanish Working Party for Blood and Marrow Transplantation in
      Children (GETMON).
AB  - INTRODUCTION: Experience with the use of allogeneic hemopoietic stem
      transplantation (AHSCT) in pediatric myelodisplastic syndrome (MDS) in Spain is
      reviewed. METHODS AND PATIENTS: Twenty-four children with MDS were analyzed
      retrospectively. Median age of the patients was 10 years. Twenty patients
      received a bone marrow graft and 4 an unrelated cord blood (UCB) transplant; 12
      bone marrow grafts were from a matched related donor (MRD) and 8 from a matched
      unrelated donor (MUD). Conditioning regimen consisted of chemotherapy alone in 17
      patients (busulfan and cyclophosphamide +/- melfalan) Seven patients received TBI
      and cyclophosphamide. RESULTS: Ten patients died from transplant-related toxicity
      and 4 had relapse or disease progression post-AHSCT. Nine patients are alive and
      event-free with a median follow-up of 120 months. EFS rate in the MRD group was
      0.48 (SE 0.13) versus 0.25 (SE 0.12) in the MUD/UCB group (p = .07). Lansky score
      in survivors is >or=90%. CONCLUSIONS: In this historical series of children with
      MDS, in spite of severe transplant-related toxicity, encouraging EFS outcomes
      have been achieved after AHSCT with good quality of life.

PMID- 19579082
TI  - Severe hypochromic microcytic anemia in a patient with congenital
      atransferrinemia.
AB  - Congenital atransferrinemia or hypotransferrinemia is a very rare autosomal
      recessive disorder, characterized by a deficiency of transferrin, resulting in
      hypochromic, microcytic anemia and hemosiderosis. The authors describe a 10-year
      old Iranian girl with hypochromic microcytic anemia. The age presentation of
      anemia was 3 months. Further evaluations indicate severe hypochromic microcytic
      anemia with decreased serum levels of iron, TIBC, and increased serum level of
      ferritin in this patient. The serum level of transferrin was decreased. The
      diagnosis of atransferrinemia was confirmed. Although atransferrinemia is a rare
      condition, it should be considered in the cases with hypochromic microcytic
      anemia, decreased serum levels of iron, TIBC, and increased serum level of
      ferritin.

PMID- 19579083
TI  - Effect of somatostatin analogue octreotide in medulloblastoma in xenograft and
      cell culture study.
AB  - BACKGROUND: The effect and possible timing of nonradiolabeled somatostatin
      analogue octreotide are still not determined in the treatment of medulloblastoma,
      while the presence of somatostatin receptor type-2 (SSTR2) is proved in the
      majority of medulloblastoma by several authors. PROCEDURES: Daoy, SSTR2A positive
      medulloblastoma cell culture was tested with octreotide in monotherapy and
      combined with cisplatin, etoposide, and vincristine. Daoy medulloblastoma mice
      xenograft was treated with octreotide alone. RESULTS: In monolayer cell culture
      high-dose octreotide (44 microM) resulted in mitotic inhibition with parallel
      increment of apoptosis. Combination with cytostatic drugs did not result in
      additive or synergistic effect, but vincristine was partially antagonized. In
      medulloblastoma xenograft, octreotide monotherapy (100 microg/kg/day for 10 days)
      resulted in partial tumor growth inhibition. CONCLUSIONS: High concentration of
      nonradiolabeled octreotide may have role in the treatment of medulloblastoma by
      long-term administration. Concomitant administration of octreotide with widely
      used cytostatic drugs against medulloblastoma will not have beneficial impact.

PMID- 19579084
TI  - Successful treatment of Kasabach-Merritt syndrome with vincristine and diagnosis
      of the hemangioma using three-dimensional imaging.
AB  - Kasabach-Merritt syndrome is a life-threatening congenital disorder characterized
      by an enlarging hemangioma, thrombocytopenia, and consumption coagulopathy. We
      report the case of a one-month male infant who presented with a large cutaneous
      tumor in his right axilla with ecchymosis, thrombocytopenia, and chronic
      consumption coagulopathy. Three-dimensional computed tomography was useful for
      accurate diagnosis of the cutaneous tumor and for determining the precise
      vascular constitution of the hemangioma, suggesting the efficacy of this method
      for diagnosing Kasabach-Merritt syndrome. Although administration of a
      corticosteroid was not effective, additional administration of vincristine
      resulted in the reversal of thrombocytopenia and coagulopathy with reduction of
      the hemangioma.

PMID- 19579086
TI  - Diabetes mellitus is associated with increased ex vivo-platelet aggregation and
      decreased response to aspirin - antithrombotic potential of ACE-inhibitors and
      AT1-antagonists.

PMID- 19579085
TI  - A novel L218P mutation in NADH-cytochrome b5 reductase associated with type I
      recessive congenital methemoglobinemia.
AB  - The presence of central cyanosis that is unrelated to cardiopulmonary causes
      alerts clinicians to a possible diagnosis of methemoglobinemia. Congenital
      methemoglobinemia due to deficiency of nicotinamide-adenine dinucleotide (NADH)
      cytochrome b5 reductase (cb(5)r) is an autosomal recessive disorder characterized
      by life long cyanosis. Here we report a six-year old boy who presented with
      central cyanosis and upon examination revealed a methemoglobin level of 19.0%.
      Sequencing the CYB5R3 gene identified a homozygous T-->C transition at base
      c.653, which changed codon 218 from leucine to proline (L218P) in cb(5)r protein.
      Treatment with ascorbic acid relieved the cyanosis and returned methemoglobin
      levels to normal.

PMID- 19579087
TI  - Qualitative research interviews.
AB  - After presenting a brief overview of the complexity of the qualitative
      interviewing process used by psychotherapy researchers, the authors discuss some
      of the major ideas that psychotherapy researchers using such interviews must
      consider both before and during the interview process. They then offer thoughts
      regarding approaches to strengthen qualitative interviews themselves.

PMID- 19579088
TI  - From single-case studies to practice-based knowledge: aggregating and
      synthesizing case studies.
AB  - Recent developments in case study methodology reflect a rising interest that
      clinicians and researchers share in building a clinically useful and empirically
      sound knowledge base from single-case studies. The present article describes
      three types of single-case studies (clinical, experimental, systematic) and
      examines their potential contributions to psychotherapy research. It then lays
      out three ways in which single-case studies can be aggregated and synthesized to
      enhance clinical understanding: (a) a case database that allows clinicians to
      efficiently search for relevant cases, (b) a metasynthesis of single-case studies
      that integrates common themes across similar cases, and (c) an individual case
      comparison method in which closely matched cases are compared to identify both
      therapeutic and hindering processes.

PMID- 19579089
TI  - Achieving trustworthiness in qualitative research: a pan-paradigmatic
      perspective.
AB  - In this article, as two researchers from different traditions in qualitative
      research (consensual qualitative research and grounded theory), the authors
      present their shared views on the critical elements of trustworthiness in
      qualitative data. In addition to making specific recommendations about the
      integrity of data, the balance between participant meaning and researcher
      interpretation, and clear communication and application of the findings, they
      identify ways in which these issues are difficult to negotiate within and across
      different qualitative approaches. The authors present examples from various
      qualitative studies, emphasize the need for a shared language to reduce confusion
      between qualitative traditions and with researchers from a more strictly
      quantitative orientation, and recommend particular approaches to establishing
      trustworthiness in qualitative research.

PMID- 19579090
TI  - Potential effects of a national consensus statement on optimal treatment of early
      rheumatoid arthritis in Ontario.

PMID- 19579091
TI  - Decreased amygdala activation during risk taking in non-dependent habitual
      alcohol users: A preliminary fMRI study of the stop signal task.
AB  - BACKGROUND AND OBJECTIVES: Habitual alcohol use is prodromal to alcohol
      dependence. It has been suggested that impairment in impulse control contributes
      to habitual drinking. Little is known whether neural processes associated with
      impulse control is altered in non-dependent social drinkers. The current
      preliminary study combined functional magnetic resonance imaging and the stop
      signal task (SST) to address this issue. METHODS: We compared non-dependent
      non/light (n = 12) and moderate/heavy (n = 9) young adult alcohol drinkers in a
      SST, in which they were required to exercise inhibitory control during the stop
      trials and were engaged in a speed/accuracy trade-off during trial-to-trial go
      responses. Our previous studies identified neural correlates of inhibitory
      control and risk taking during the SST ( [10] , [11] ). Furthermore, alcohol
      dependent patients showed altered brain activation both during inhibitory control
      and risk taking, compared to healthy controls ( [12] ). RESULTS: We showed that
      moderate/heavy alcohol drinkers were decreased in amygdala activation during risk
      taking, while indistinguishable in neural measures of inhibitory control, when
      compared to non/light drinkers. CONCLUSIONS AND SIGNIFICANCE: Altered amygdala
      activation during risk taking may be a key neural process underlying early
      habitual alcohol use and a potential marker mediating transition to alcohol
      dependence.

PMID- 19579092
TI  - Treatment entry among individuals on a waiting list for methadone maintenance.
AB  - BACKGROUND: Many methadone programs in the United States have waiting lists for
      care. OBJECTIVES: To examine specific predictors of treatment entry among
      individuals on a waiting list for methadone maintenance. METHODS: Heroin users
      placed on a waiting list for methadone treatment (n = 120) were administered a
      urine screen for drug use and assessed with a battery of measures at study entry
      and at 4 month follow-up as part of a larger clinical trial. Logistic regression
      was used to examine hypothesized predictors of treatment entry. Outcomes for
      those failing to enter treatment were also examined. RESULTS: Only 25 individuals
      (20.8%) entered treatment within four months of being placed on a waiting list.
      Intravenous drug users were more likely to enter treatment (p <.05) whereas
      cocaine users were less likely to do so (p <.01). Motivation did not predict
      treatment entry, and cocaine use did not moderate this relationship. There were
      some improvements in heroin use among those who did not enter treatment.
      CONCLUSIONS: Additional research is needed on the relationship between motivation
      and treatment entry. Programs may need to make special efforts to facilitate
      entry for treatment-seeking heroin users who also use cocaine. SCIENTIFIC
      SIGNIFICANCE: These findings have implications for improving access to methadone
      treatment.

PMID- 19579093
TI  - Does taking steps to control one's drug use predict entry into treatment?
AB  - BACKGROUND: Treatment readiness has been shown to predict entry and success in
      drug treatment programs. OBJECTIVE: To examine the association between treatment
      readiness (defined as engaging in activities to control one's drug use) and
      enrolling in drug treatment. METHODS: Longitudinal data collected through face-to
      face interviews (March 2004-February 2007, NIDA-funded) from 585 injectors in
      Baltimore were analyzed. RESULTS: Avoiding buying drugs and drug-related people
      and places were associated with entering treatment at follow-up. Also, the more
      activities one engaged in, the greater likelihood of entering drug treatment.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These findings suggest that practicing
      behaviors to control one's drug use may be a beneficial strategy for getting
      ready for treatment.

PMID- 19579096
TI  - Dental and skeletal growth in early fossil hominins.
AB  - Early fossil hominins have often been assigned a chronological age on the basis
      of modern human data for tooth eruption. Better data and more sophisticated
      methods are now available to estimate their chronological age from modern human
      standards for stages of mineralization of individual teeth developing within the
      jaws. However, while comparisons with modern human dentitions are interesting,
      they can also be misleading as early hominin teeth and dentitions did not grow
      like modern human teeth. Chronological age can also be estimated using the
      microanatomy of tooth enamel and root dentine. Counts of incremental markings in
      enamel predict much younger ages at death for early fossil hominins than those
      based on modern human radiographic standards of dental development. Comparative
      evidence from the skeleton suggests that a greater proportion of adult body mass
      and stature was achieved earlier in the growth period of fossil hominins than it
      is in modern humans. The combined skeleto-dental evidence provides the basis for
      a hypothesis that the earliest hominins grew more like modern great apes, but
      that Homo erectus had a slightly more prolonged period of growth, and which was
      still not totally modern human-like in its pattern or timing.

PMID- 19579097
TI  - Creating Futures.

PMID- 19579098
TI  - Creating better futures: when the theory fails and the future is no more.
AB  - OBJECTIVE: The aim of this paper is to advance and enrich innovative thinking
      about mental health issues from an Indigenous perspective, through consideration
      of the gap between Indigenous mental health research and Indigenous mental health
      practice.

PMID- 19579099
TI  - A human rights based approach to social and emotional wellbeing.
AB  - From July 2004 Tom Calma has been the Aboriginal and Torres Strait Islander
      Social Justice Commissioner at the Australian Human Rights Commission. This role
      was created in 1992 to provide an ongoing monitoring agency for the human rights
      of Indigenous Australians and involves, inter alia, producing the Social Justice
      Report, an annual account to the Federal parliament on the status of enjoyment
      and exercise of human rights by Indigenous Australians. Commissioner Calma gave
      the opening oration to the 2006 Creating Futures conference and returned to open
      the conference in 2008 on 22 September in St Albans Anglican Church, located in
      the Aboriginal community of Yarrabah, 60 kilometres from Cairns. This is the text
      of that speech.

PMID- 19579100
TI  - 'Living between two worlds': who is living in whose worlds?
AB  - OBJECTIVE: Indigenous people have often been depicted as 'living between two
      worlds'. They have been described as living neither in their 'Indigenous' world
      nor in the 'Western' world but in some middle, liminal, or in-between 'world'.
      People in such situations are often described as 'caught' or 'suspended' and with
      obvious negative social, emotional and health consequences. What is this cultural
      space that is often described as 'being between two worlds'? Can Indigenous
      people develop their identity within the demands and values of contemporary
      Australian society? CONCLUSIONS: Most people who live within the context of
      modernity move across a mixture of different social, spiritual and cultural
      'worlds'. By projecting particular and negative meanings onto Indigenous people
      and their journey of identity, non-Indigenous people diminish the value of
      Indigenous energies and initiatives in attempting to cope with life's diverse
      pressures and expectations. The perpetuation of such attitudes serves to
      undermine the efforts that Indigenous people make to engage modernity while at
      the same time attempting to maintain values that are of critical importance for
      their health and wellbeing. Consequently, non-Indigenous people can end up
      diminishing the importance of their own life transitions.

PMID- 19579094
TI  - Dysregulation of maternal serum adiponectin in preterm labor.
AB  - OBJECTIVE: Intra-amniotic and systemic infection/inflammation have been causally
      linked to preterm parturition and fetal injury. An emerging theme is that adipose
      tissue can orchestrate a metabolic response to insults, but also an inflammatory
      response via the production of adipocytokines, and that these two phenomenons are
      interrelated. Adiponectin, an insulin-sensitising, anti-inflammatory
      adipocytokine, circulates in multimeric complexes including low-molecular weight
      (LMW) trimers, medium-molecular weight (MMW) hexamers and high-molecular weight
      (HMW) isoforms. Each of these complexes can exert differential biological
      effects. The aim of this study was to determine whether spontaneous preterm labor
      (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is
      associated with changes in maternal serum circulating adiponectin multimers.
      STUDY DESIGN: This cross-sectional study included patients in the following
      groups: (1) normal pregnant women (n=158); (2) patients with an episode of
      preterm labor and intact membranes without IAI who delivered at term (n=41); (3)
      preterm labor without IAI who delivered preterm (n=27); and (4) preterm labor
      with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW,
      MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics
      were used for analyses. RESULTS: (1) Preterm labor leading to preterm delivery or
      an episode of preterm labor that does not lead to preterm delivery was associated
      with a lower median maternal serum concentration of total and HMW adiponectin, a
      lower median HMW/total adiponectin ratio and a higher median LMW/total
      adiponectin ratio than normal pregnancy; (2) among patients with preterm labor,
      those with IAI had the lowest median concentration of total and HMW adiponectin,
      as well as the lowest median HMW/total adiponectin ratio; (3) the changes in
      maternal adiponectin and adiponectin multimers remained significant after
      adjusting for confounding factors such as maternal age, BMI, gestational age at
      sampling and parity. CONCLUSION: (1) Preterm labor is characterised by a change
      in the profile of adiponectin multimers concentrations and their relative
      isoforms. These changes were observed in patients with an episode of preterm
      labor not leading to preterm delivery, in patients with intra-amniotic
      inflammation, or in those without evidence of intra-amniotic inflammation. (2)
      The changes in adiponectin multimer concentrations reported in preterm labor are
      different from those previously reported in spontaneous labor at term, suggesting
      that there is a fundamental difference between preterm labor and labor at term.
      (3) The findings reported herein provide the first evidence for the participation
      of adiponectin multimer in preterm parturition. We propose that adiponectins and
      adipokines in general provide a mechanism to organise the metabolic demands
      generated by the process of preterm parturition regardless of the nature of the
      insult (intra-amniotic inflammation or not).

PMID- 19579101
TI  - Who is not coping with colonization? Laying out the map for decolonization.
AB  - OBJECTIVE: This paper explores reasons for using decolonization as a method for
      improving Indigenous health status. Decolonization is a method required to shift
      the current paradigm of Western dominance and colonial amnesia that constructs
      and maintains Indigenous poor health status. CONCLUSION: Decolonization requires
      every Australian to examine the impact colonization has upon their past and
      present in order to formulate a future that does not reinstate the past. To take
      these steps requires a balance of histories, informing our current political and
      social context, critical reflexive practice and open communication with
      Aboriginal and Torres Strait Islander peoples.

PMID- 19579102
TI  - The experience of collective trauma in Australian Indigenous communities.
AB  - OBJECTIVE: The concept of collective trauma has predominantly been applied in the
      context of natural and human disasters. This paper seeks to explore whether
      collective trauma offers a respectful way in which to explore and respond to
      mental health and wellbeing issues for Aboriginal families and communities.
      METHOD: A review of the international literature was undertaken in order to
      determine the elements of collective and mass trauma studies which may have
      relevance for Indigenous communities in Australia. RESULTS: Findings support the
      proposition that the patterns of human responses to disasters, particularly in
      protracted traumas such as war-zones, shows strong parallels to the contemporary
      patterns of experience and responses articulated by Aboriginal people affected by
      colonization and its sequelae in Australia. CONCLUSION: Adopting evidence
      informed principles of family and community healing developed internationally in
      disaster situations may provide helpful ways of conceptualizing and responding in
      a coordinated way to mental health and wellbeing issues for Indigenous people
      within Australia.

PMID- 19579103
TI  - A psychoanalytic exploration of collective trauma among Indigenous Australians
      and a suggestion for intervention.
AB  - OBJECTIVE: Psychoanalysis is used to explore the effects of the annihilation of
      culture and how this leads to a loss of identification with a collective
      subjectivity and triggers catastrophic symptoms including loss of collective
      hope, the rise of addictive and self-destructive behaviours, and the
      intergenerational transmission of trauma among Indigenous Australian communities.
      CONCLUSIONS: I propose restorative educational interventions for young Indigenous
      children that seek to engage them with ancestral memory, cultural narratives, and
      a sense of purpose so that healing from historically transmitted trauma may be
      initiated and a grounded sense of subjectivity restored.

PMID- 19579104
TI  - Boys becoming men: what makes a difference?
AB  - OBJECTIVE: In 1983 an Under 17 Australian Rules Football team visited Melbourne.
      They came from Townsville in North Queensland and the majority were Aboriginal
      and Torres Strait Islander. For several months prior to the trip they worked to
      raise the money and resources they needed for the trip. This paper describes the
      preliminary results of a research project that looked at the health of this group
      25 years later. What can we learn from their experience in 1983? What can they
      tell us about the health of the next generation of young Aboriginal and Torres
      Strait Islander men? METHOD: The research project used a mixture of quantitative
      and qualitative research methods. It included a questionnaire, interviews,
      workshop and a focus group. RESULTS: All of those involved in 1983 are still
      alive. Over a range of social and economic indicators many score very well but
      there are signs, as with other Aboriginal and Torres Strait Islander men, of
      underlying health issues. CONCLUSIONS: Sport can provide for young Aboriginal and
      Torres Strait Islander men a culturally 'safe' place where important values
      across generations are developed and sustained.

PMID- 19579105
TI  - The insidious problem inside: mental health problems of Aboriginal and Torres
      Strait Islander People in custody.
AB  - OBJECTIVE: Despite recognition of the extremely high rates of mental illness
      among custodial populations and the fact that Indigenous people represent around
      one-quarter of Australia's custodial population, little is known about the mental
      health of Aboriginal and Torres Strait Islander people in custody. Mental health
      is an important component of social and emotional wellbeing for Indigenous people
      and this paper considers current evidence regarding the mental health status of
      Indigenous Australians in custody. METHOD: A systematic review was undertaken of
      the quantitative literature relating to the mental health problems of Indigenous
      people in custody in Australia. RESULTS: Despite high incarceration rates for
      Indigenous people and evidence that both mental health problems and rates of
      mental illness are extremely high in this group, studies in this area are few and
      limited in scope. CONCLUSION: The first step toward addressing the marked social
      and mental health problems for Indigenous people in custody is to systematically
      identify the nature and extent of these problems.

PMID- 19579107
TI  - Ethical research in partnership with an Indigenous community.
AB  - OBJECTIVE: The aim of this paper is to describe the implementation of the
      Community Safety Research Project (CSRP) focusing on violence prevention among
      Aboriginal communities in western NSW in order to examine how practice converges
      with contemporary ethical guidelines. METHOD: A comparison was made of key
      project elements with the principles outlined in existing ethical guidelines,
      outlining the concrete issues that need to be confronted in practice. RESULTS:
      The approach being pursued is consonant with the principles of contemporary
      guidelines; the results of the first phase qualitative study inquiring into
      workers' perceptions of violence revealed some differences in the understanding
      of violence between Aboriginal and non-Aboriginal workers, with some ethical
      implications. CONCLUSIONS: Ethical approaches to research among Aboriginal
      communities include, but extend well beyond, the principle of avoiding harm. A
      comprehensive approach to ethical research requires significant ongoing
      expenditure of effort and resources with implications for project development,
      management and funding.

PMID- 19579106
TI  - The importance and challenges of assessing cognition in Indigenous Australians.
AB  - OBJECTIVES: The aim of this paper was to investigate the importance and
      challenges involved in conducting serial cognitive assessments among healthy
      Indigenous adolescents. METHOD: Cognitive assessments were conducted at
      fortnightly intervals for 2 months and again at 6 and 12 months among a group of
      Indigenous students from a boarding school in the Northern Territory. These
      students were to be the healthy control group in a long-term study of substance
      abuse. Recruitment and attrition rates were reviewed and related challenges for
      assessing participants were identified. RESULTS: From the recruited sample
      (n=49), 18% reported heavy or frequent use of alcohol, cannabis or petrol. Males
      were more likely to have used these substances compared to females. Attrition
      increased as the follow-up interval increased with 49 recruits reducing to 32 in
      the first 2 months and only 15 and 13 of the initial group remaining for the 6
      and 12 month follow-ups respectively. CONCLUSIONS: Main challenges included (i)
      appropriateness of tests and assessment processes, (ii) high rates of substance
      abuse and other illness in the control group and (iii) high attrition rates. The
      importance of assessing cognition appropriately is highlighted by a lack of
      information regarding mental health issues in Indigenous populations.

PMID- 19579108
TI  - Listening, sharing understanding and facilitating consumer, family and community
      empowerment through a priority driven partnership in Far North Queensland.
AB  - OBJECTIVES: This paper provides an example of a mental health research
      partnership underpinned by empowerment principles that seeks to foster strength
      among community organizations to support better outcomes for consumers, families
      and communities. It aims to raise awareness among researchers and service
      providers that empowerment approaches to assist communities to address mental
      health problems are not too difficult to be practical but require long-term
      commitment and appropriate support. METHODS: A collaborative research strategy
      that has become known as the Priority Driven Research (PDR) Partnership emerged
      through literature review, consultations, Family Wellbeing Program delivery with
      community groups and activities in two discrete Indigenous communities. Progress
      to date on three of the four components of the strategy is described. RESULTS:
      The following key needs were identified in a pilot study and are now being
      addressed in a research-based implementation phase: (i) gaining two-way
      understanding of perspectives on mental health and promoting universal awareness;
      (ii) supporting the empowerment of carers, families, consumers and at-risk groups
      through existing community organizations to gain greater understanding and
      control of their situation; (iii) developing pathways of care at the primary
      health centre level to enable support of social and emotional wellbeing as well
      as more integrated mental health care; (iv) accessing data to enable an ongoing
      process of analysis/sharing/planning and monitoring to inform future activity.
      CONCLUSION: One of the key learnings to emerge in this project so far is that
      empowerment through partnership becomes possible when there is a concerted effort
      to strengthen grassroots community organizations. These include social health
      teams and men's and women's groups that can engage local people in an action
      orientation.

PMID- 19579109
TI  - 'Bringing back respect': the role of participatory action research in
      transferring knowledge from an Aboriginal men's group to youth programs.
AB  - OBJECTIVE: This case study describes the efforts of an Aboriginal men's group to
      facilitate and support the empowerment of young people in their community. It is
      part of a broader participatory action research (PAR) study of men's groups.
      METHOD: Data was derived from quarterly reflective PAR sessions with men's and
      youth workers and steering committee members, interviews with workers, and focus
      groups with young people. The data was coded and categorized, with five themes
      identified. RESULTS: Key opportunities and challenges related to building staff
      capacity, engaging young people, giving voice to young people and reconciling
      diverse community views. Emerging outcomes included young people's definition of
      vision and values, social cohesion, personal achievements and recognition. The
      youth projects also resulted in local employment, improvements in workforce
      capacity and proposals to extend the empowerment model in Yarrabah and transfer
      it to another community. CONCLUSION: PAR frameworks provide a useful tool for
      facilitating and sustaining empowerment outcomes. They can be used to support the
      transfer of knowledge and skills from one Aboriginal community group to another.

PMID- 19579111
TI  - Reflections on a community and university research collaboration.
AB  - OBJECTIVE: This paper reflects on the collaborative research relationship between
      university and community researchers. It identifies emergent themes expressed in
      the words of researchers and recommends strategies to assist with other research
      collaborations. CONCLUSIONS: Emergent themes included: Initial reticence by
      community members followed by positive experiences; the value of empowerment
      frameworks in research; building trust between community and university
      researchers; capacity building, management, and workloads; and community
      politics, misunderstandings and wealth disparity. The paper recommends strategies
      for successful research collaborations and identifies challenges to research
      collaborations.

PMID- 19579110
TI  - The healing journey: empowering Aboriginal communities to close the health gap.
AB  - OBJECTIVES: This paper presents two arguments relevant to both past and present
      efforts to improve Indigenous health. It advocates for ways of thinking about and
      doing health promotion that begin with empowerment to help people gain a greater
      level of control over their lives and circumstances. CONCLUSION: A combination of
      the strengths of different approaches is in fact an empowering, dialectical view
      that can be achieved by considering Aboriginal people not as children in need,
      but as capable and efficacious individuals.

PMID- 19579112
TI  - Using policy and workforce development to address Aboriginal mental health and
      wellbeing.
AB  - OBJECTIVE: The aim of this paper is to discuss the New South Wales (NSW)
      Aboriginal Mental Health and Well Being Policy and its key workforce initiative,
      the NSW Aboriginal Mental Health Workforce Training Program. CONCLUSIONS: The
      Policy provides a strong framework guiding the development of Aboriginal mental
      health and wellbeing programs throughout NSW Mental Health Services. However, the
      effectiveness of the Policy will be determined by the success of its
      implementation. The NSW Aboriginal Mental Health Workforce Training Program will
      support implementation of the Policy by growing an Aboriginal mental health
      workforce in NSW.

PMID- 19579113
TI  - The development of an 'Indigenous team' in a mainstream mental health service in
      South Australia.
AB  - The Social Justice Report 2005 recommended that the governments of Australia
      commit to achieving equal health status for all Australians "within a
      generation". Improving the accessibility of mainstream health services for
      Aboriginal people is highlighted as a central requirement. This paper describes
      the establishment, roles and functions of the 'Indigenous team' embedded within
      the South Australian Rural and Remote Mental Health Service (RRMHS) as one
      strategy to improve access and responsiveness of mental health services to
      Aboriginal patients in South Australia. We report on our progress to date and
      possible future directions for the team.

PMID- 19579114
TI  - Working with a community controlled health organization to develop an evidence
      base for their practice models.
AB  - OBJECTIVE: The aim of this paper is to present a model of working with a
      community controlled health organization to develop an evidence base that will be
      used to inform program development and delivery. RESULTS: Through the examination
      of this and other models health professionals can find answers to questions
      around how to gather evidence of how interventions work (or do not work), for
      whom and in what circumstances. Using evidence of this kind to inform planning
      processes and decision making will facilitate improved, sustained health outcomes
      for Aboriginal and Torres Strait Islander peoples in the future.

PMID- 19579115
TI  - Widening the circle: making Mental Health Review Tribunal hearings accessible in
      Indigenous, rural and remote settings.
AB  - OBJECTIVE: The aim of this paper is to overview the history, structure and
      activities of the Queensland Mental Health Review Tribunal in relation to
      Indigenous patients. RESULTS: The Mental Health Review Tribunal is an independent
      statutory body established under the Mental Health Act 2000 (MHA2000) to
      safeguard the rights of patients receiving involuntary treatment under the
      Queensland MHA2000. In the period from when the Tribunal commenced in 2002 to end
      of June 2008, people of Aboriginal and Torres Strait Islander background
      represent 2.3% of all patient registrations with the Tribunal. The Tribunal has
      established a range of strategies to encourage Aboriginal and Torres Strait
      Islander patients to attend and participate in their hearing. This includes
      widening the Tribunal's body of knowledge, strategies to inform patients about
      the Tribunal, culturally sensitive hearing practices, and widening the circle of
      participation in the hearing. CONCLUSIONS: The future direction for the Tribunal
      in this strategy will be influenced by more formal evaluation of the outcomes and
      by further development of a model for the provision of cultural advice.

PMID- 19579117
TI  - "The Sergeant wants to acupuncture me": a personal lens into the introduction of
      a traditional Eastern therapy to Indigenous Australians.
AB  - OBJECTIVE: This paper introduces a project established between the Emotional,
      Social Wellbeing Centre and the Goldfields Ngunytju Tjitji Pirni (Caring for
      Women and Children) and the Western Australia Police in Kalgoorlie, Western
      Australia. CONCLUSIONS: Members of the Indigenous community of Kalgoorlie have
      found benefit through consultation and treatment involving the use of
      acupuncture, dietary and lifestyle counselling. In addition, Indigenous persons
      have found benefit in an alternative means of accessing police services outside
      of a typical police environment.

PMID- 19579116
TI  - The Napranum social and emotional wellbeing week.
AB  - OBJECTIVE: A week-long intensive outreach project to the Indigenous community of
      Napranum was undertaken by a Community Forensic Mental Health Service with the
      aim of developing the community's capacity for primary and secondary prevention
      of forensic mental health problems. METHOD: The process of developing and
      implementing the project is described. The outcome is evaluated by means of
      qualitative feedback from community members and participants. RESULTS: The
      project was requested by the local community; planning involved extensive
      consultation between Queensland Health, community leaders and local service
      providers; and it was delivered with extensive contributions from other
      Queensland Health services, various non-government organizations, Indigenous
      opinion-leaders and public media, and an NRL football team. The outcomes are
      sustainable at a local level. CONCLUSIONS: This form of community engagement may
      contribute to destigmatization of mental illness in Indigenous communities,
      increased engagement between these communities and mental health service
      providers, and increased cohesiveness and morale of these communities.

PMID- 19579118
TI  - Undertaking a Fellowship in Indigenous mental health.
AB  - OBJECTIVE: The aim of this paper is to report the experiences of the author
      during her Advanced Training Fellowship year in Indigenous mental health and
      consultation-liaison psychiatry through the Royal Australian and New Zealand
      College of Psychiatry. The description will include a discussion of how such a
      Fellowship may complement the key learning objectives of advanced training in
      psychiatry. CONCLUSIONS: A Fellowship in Indigenous mental health can offer a
      variety of experiences for the psychiatry trainee, including clinical work,
      research and teaching. The planning and collaboration with Aboriginal health
      organizations, key clinicians and Ethics committees provides a unique opportunity
      to learn invaluable communication and consultancy skills.

PMID- 19579119
TI  - Social and emotional wellbeing training of psychiatrists in Victoria: preliminary
      communication.
AB  - OBJECTIVES: The aim of this paper is to document the processes towards ensuring
      that all psychiatrists in training in Victoria have appropriate Indigenous mental
      health experience and training. CONCLUSIONS: This paper describes the process of
      implementation of the 2004 Indigenous Mental Health Royal Australian and New
      Zealand College of Psychiatrists (RANZCP) Training By-Laws within Victoria. It is
      likely that the challenges of ensuring access to this training experience, within
      the Victorian RANZCP Training Program, have been experienced to varying degrees
      within other Australian training programs. The vertical integration of Indigenous
      health curriculum extends work being done in all undergraduate medical schools in
      Australia and New Zealand, and which the Australian Medical Council have
      incorporated into their accreditation of medical schools.

PMID- 19579120
TI  - Whakaora nga moemoea o nga tupuna--living the dreams of the ancestors. Future
      planning in a Kaupapa Maori CAMHS team.
AB  - OBJECTIVE: The aim of this study was to identify and operationalize aspects of a
      future planning process for sustainable delivery of Kaupapa Maori (Specialist
      Maori) mental health from a team called He Kakano, within Child and Adolescent
      Mental Health Services in South Auckland, New Zealand. METHODS: A 2-day hui
      (meeting) was held with members of the team and a facilitator, Whaea Moe Milne.
      Review of background national epidemiological data, local data, information from
      community, carer and tangata whaiora (consumer) stakeholders and the existing He
      Kakano Model of Care was undertaken. Use of tikanga (Maori protocol and
      practices) was evident throughout the hui. RESULTS: A number of aspects of
      tikanga were identified as essential to the positive outcomes of the future plan.
      This paper reports one in particular, that of whakatauaki (proverbs where the
      originator is known). "Whakaora nga moemoea o nga tupuna--living the dreams of
      the ancestors" is a whakatauaki articulated by Whaea Moe Milne, which was
      identified as helpful in influencing the strategic planning thinking and decision
      making process for He Kakano. This whakatauaki enabled the identification of
      shared goals, values, beliefs, behaviours and an action plan. The existing and
      ongoing relationship with Whaea Moe Milne was identified as an important element
      in the way in which the whakatauaki was received and reflected on. CONCLUSIONS:
      Use of tikanga Maori, in this case, whakatauaki, was helpful in developing future
      planning for He Kakano. This suggests that use of tikanga may be beneficial in
      other settings where planning for sustainable Maori responsive services is
      undertaken. Further work in this area is likely to benefit service development,
      strategic planning, workforce development and have an impact on improving health
      outcomes for Maori.

PMID- 19579121
TI  - Promoting traditions: an evaluation of a wilderness activity among First Nations
      of Canada.
AB  - OBJECTIVES: Several native American communities face serious social problems
      brought about by the loss of culture. Many First-Nation communities organize
      traditional activities in a wilderness setting to promote culture and prevent
      social problems, among them suicide. The activities evaluated in this study were
      organized by the Atikamek community of Manawan (Quebec, Canada) for adolescents
      aged between 14 and 17 years. The main goals of these activities were to increase
      self-esteem, re-establish cultural continuity, encourage pro-social behaviours
      among the participants and ultimately empower and mobilize the community.
      METHODS: Within the context of an honours thesis project, this research assessed
      the process and the effects of these traditional activities on a group of First
      Nation youth. The evaluation used a mixed methodology consisting of two self
      esteem scales and participatory observation. The results of this evaluative study
      show that this type of traditional activity is an innovative tool to increase
      cultural pride, foster pro-social behaviour and empower First-Nation youth.
      CONCLUSIONS: Obstacles met during the course of this research project highlight
      the importance of developing methodologies able to capture the rich and specific
      outcomes of traditional activities in an Aboriginal context.

PMID- 19579122
TI  - Informing and implementing policy to advance mental health and wellbeing through
      action research in a rural remote community mental health setting.
AB  - OBJECTIVES: The aim of this study was to work collaboratively with a rural
      Community Mental Health Team (CMHT) to examine the issue of workplace stress and
      address issues specified by the group. METHOD: A five stage action research
      method following the Susman and Evered Model of Change was implemented for this
      research with four distinct cycles completed. RESULTS: A cyclic process of action
      research established that organizational policies, clinical skills and
      educational levels of staff were inadequate. Two overarching themes drove the
      research cycles: staff safety and inadequate education of nursing staff to assess
      and appropriately manage consumers with mental health issues. CONCLUSIONS: This
      study found that unsafe environmental conditions in the health workplace and
      limited staff knowledge contributed to workplace stress. Staff identified as
      vital strategies to manage aggressive or potentially aggressive incidents
      effectively and ensure staff and client safety. Managers, policy makers and
      government officials need awareness of the threats to healthy workforces. Tools
      to guide practice and staff education were implemented to address the identified
      problems.

PMID- 19579124
TI  - The promise of online cognitive behavioural therapy training for rural and remote
      mental health professionals.
AB  - OBJECTIVE: The aim of this paper is to indicate how online cognitive behavioural
      therapy (CBT) training for rural and remote health professionals can enhance
      access to evidence-based treatments in rural communities and address
      psychotherapy training shortfalls for rural practitioners treating Australians
      with high prevalence psychological disorders. CONCLUSIONS: Issues of cost,
      distance and disruption to services have meant that, until now, it has been very
      difficult to provide really effective training in evidence-based therapies (in
      the main, CBT) for Australian rural and remote health professionals. The recent
      development of online CBT training provides new opportunities. Online training,
      supplemented by regular supervision, can fulfil many of the functions of face-to
      face training at significantly reduced cost. While face-to-face residential
      workshops will still be necessary to embed new skills, we estimate that online
      training can reduce the face-to-face time required by at least 50%.

PMID- 19579123
TI  - Enhancing the knowledge and skills of Advisory and Extension Agents in mental
      health issues of farmers.
AB  - OBJECTIVES: The aim of this study was to increase knowledge and skills of
      Advisory and Extension Agents (AEAs) in recognizing the symptoms of mental
      disorders, providing initial help, and offering the referral pathway for
      appropriate professional help. METHOD: Mental Health First Aid (MHFA) training
      was provided to AEAs and knowledge and skills pre-training were compared to 6
      months post-training. RESULTS: The MHFA training improved the AEAs' ability to
      recognize a mental disorder, it increased their confidence level in providing
      help to someone with a mental health problem, it decreased social distances and
      positively changed their beliefs about treatment. CONCLUSION: MHFA training is
      effective in enhancing the mental health knowledge and skills of AEAs. The
      agents, who are a main line of contact of farmers, are able to recognize mental
      disorders of people and help them appropriately. They are more willing to work
      with stigmatized people and know who to refer people to for help.

PMID- 19579125
TI  - Incorporating sociocultural beliefs in mental health services in Kwaio, Solomon
      Islands.
AB  - OBJECTIVE: The aim of this paper is to describe the newly established mental
      health services at Atoifi Adventist Hospital, Solomon Islands, the sociocultural
      context in which it operates, and illustrate how the service is engaging with the
      Kwaio community to understand and incorporate local sociocultural beliefs into
      prevention, treatment and recovery journeys. METHOD: Five remote hamlets in East
      Kwaio, Malaita Province were visited in early 2008. Interviews were undertaken
      with 20 people with a history of buru spirit possession and 30 of their family
      members. RESULTS: Buru is a category of wild and malevolent spirits that possess
      people in East Kwaio and induce antisocial and unexpected behaviour. Signs of
      buru possession include mutism, suicidal ideas, delusion, aggression and social
      isolation. Traditional healers practice indigenous treatments with 50% of people
      receiving treatments described as cured, 30% temporary cured and 20% no effect
      from treatment. CONCLUSIONS: The new mental health service at Atoifi is taking
      steps to incorporate sociocultural beliefs, including of people possessed by
      buru, into routine practice. This provides a greater potential to support
      prevention, treatment and recovery journeys to advance the community's social,
      emotional and spiritual wellbeing.

PMID- 19579126
TI  - Dua sakit (double sick): trauma and the settlement experiences of West Papuan
      refugees living in North Queensland.
AB  - There is mounting evidence of systematic abuses, including torture, rape and
      extrajudicial killings directed against independence activists as well as the
      civilian population in Indonesian occupied West Papua. Refugees from West Papua
      have sought safety in neighbouring Australia, experiencing hazardous journeys
      during their flight. We report early observations from a mental health study
      among West Papuan refugees living in North Queensland, Australia. The project
      includes qualitative methods aimed at gathering histories of trauma and human
      rights violations as well as standard mental health assessments and indices of
      acculturation and resettlement stresses. We consider the emerging data from the
      vantage point of the Adaptation and Development After Persecution and Trauma
      model that identifies five psychosocial domains that require repair following
      exposure to gross human rights violations and refugee trauma. The model
      emphasizes the inter-relatedness of key challenges, the compounding of adversity,
      and the bivalent effects of complex experiences, with both positive and negative
      elements shaping the adaptive trajectory of displaced persons. Refugee groups
      have their own approaches to conceptualizing the complexity of their problems,
      with the term dua sakit representing the expression used by West Papuans to
      identify the multiple challenges they face. The study highlights the importance
      of assessing each refugee group within its unique social and cultural context,
      taking into account such diverse factors as geographical location, employment,
      and ongoing conflict in the homeland in designing appropriate interventions.

PMID- 19579127
TI  - Applied theatre: performing the future.
AB  - OBJECTIVE: This paper provides an introduction to applied theatre and performance
      as a body of practice that may enhance the wellbeing of Indigenous communities.
      Applied theatre forms are conceptualized along a continuum from 'performance
      oriented' to 'participant-oriented'. Participant reflections are reported from a
      pilot workshop in Papua New Guinea, as a contribution to the evolution of theory
      and practice of applied theatre for health promotion in Indigenous communities.
      METHODS: Twelve Papua New Guinean nationals engaged in health promotion
      participated in the workshop. Participants were invited to reflect on the
      potential application of the theatre forms for their own health promotion
      practice. The workshop was qualitatively evaluated through a focus group at the
      conclusion of the workshop. RESULTS: Participants identified specific theatre
      forms which they could use in their own health promotion practice. Several
      participants articulated a view that participant-oriented forms were more likely
      to influence health-related behaviour than performance-oriented forms, in their
      cultural context. CONCLUSIONS: The theatre-for-development literature does not
      yet clearly articulate how specific theatre forms may be more or less efficacious
      in terms of influencing health-related behaviour across cultural contexts. More
      extensive research into this question will yield significant benefits in terms of
      focusing practice culturally.

PMID- 19579128
TI  - Building communities through performance: emerging approaches to
      interculturality.
AB  - OBJECTIVE: Changing definitions of culture are modifying approaches to
      intercultural education and training. This paper outlines the principal features
      of these emerging models for innovation and capacity building in communities.
      METHODS: Semiotics provides a theoretical frame for the interdisciplinary
      analysis of research on cultural competency, especially regarding recent studies
      on "cultural intelligence", performance and creativity. RESULTS:
      Interdisciplinary research on cultural literacy is shifting from cultural
      knowledge to intercultural know-how. This know-how translates into the
      individual's capacity to innovate and illustrates the influence of culture on
      individual and group performance. CONCLUSIONS: Research on cultural intelligence,
      performance and creativity provides promising new models for capacity building in
      communities. These approaches constitute a synthesis of previous research on
      cultural competency and provide new avenues for innovative social action through
      intercultural exchange.

PMID- 19579129
TI  - How the all fruits salad creates sweeter futures in rural and remote mental
      health.
AB  - OBJECTIVE: This paper outlines evidence of efficacious outcomes from mixing
      people living with diverse mental health challenges and/or intellectual
      disability. The intention was to show how mixing up people who are differently
      challenged can be efficacious in (re)habilitation terms. Two separate experiences
      of sharing personal narratives were involved, along with creative expressions in
      music, art and filming, combined with group gatherings providing discerning
      feedback for each other on members' day-to-day progress. After 12 months of 'open
      urban tribe' gatherings in Sydney, where participants formed a community of
      belonging, the model was adapted for use in Alice Springs. The original group
      developed a cycle of interactive ritual rhythms, and these became a special
      feature of their self-help, peer support approach. The Sydney project modelled
      community-based rehabilitation, and that process then informed the processes
      initiated in a rural, remote location. METHODS: Regular whole tribe gatherings
      'in the circle' combined with mentoring 'aunties and uncles'. By sharing stories
      and giving personal feedback on their progress, participants developed skills and
      confidence in self expression. Relating to each other and the group, and sharing
      creative expressions (group craft activities, dancing, small group performing)
      added depth to the experience of participants. Stories and celebrations were
      filmed, along with meetings to discuss progress and reflect on how to improve our
      process of sharing together. Ways for individuals to work on improving their life
      experiences were shared across the group, which generated a combination of forms
      of inquiry: supportive, collaborative and appreciative. These were combined with
      reflexive qualitative ethnographic recording by the researcher, to report and
      reflect on the whole process. RESULTS: The original 12 month open urban tribe
      formation (May 2004-June 2005) in Sydney led to regular gatherings where
      participants sought to come together and celebrate their being with each other
      until 2007. From that model further work was undertaken in Alice Springs in early
      2008, applying a smaller version of this approach to a new community group. The
      narrative testimony and witnessing in the first group formed one element of what
      participants called 'the magic', which they commented on throughout their time
      together. It was their way of just being together (what this author calls their
      'metaphorical energetic presence' alongside each other) that carried the power of
      this tribe's interactions. Mirroring and feeding back messages to each other that
      they belonged, that they had an identity, role and purpose together, was a key
      influence on wellness. That they were seen and loved by all participants was a
      vital element in the dynamic. These combined to create an effect dubbed 'Working
      the Business of Life' (WTBOL), a group sharing process providing practical
      feedback on how to maintain balance in life. By giving everyone a sense of being
      nurtured in their day-to-day lives, WTBOL showed that people of mixed
      consciousness can assist each other's healing, growth and development. The value
      in mixing people of different challenges was that it created a rich field of
      exchange of their beingness, and mutual appreciation and support. Each had
      compassion for the other's challenge, and this helped their own process of
      growing beyond their own challenges. The process has now been successfully
      applied in Peer Support Training Workshops for Consumers and Carers (November
      2008 in Alice Springs). CONCLUSIONS: Arising from this work, the All Fruits
      Theory (AFT) argues that mixing people of diverse consciousness, in contexts of
      trust and safety with each other, can lead to enriching personal acknowledgement
      and a sense of belonging. By sharing stories, joining celebratory activities, it
      is possible to generate interactive rhythmical ritual cycles of companionship,
      celebration, communion and contemplation. The project thus stimulated purposeful
      motivation and intention to engage in new activities. Individual and group social
      and emotional wellbeing were enhanced by participating. The author argues that
      these results show that, just as biodiversity is essential for ecological
      sustainability, 'onto-diversity' (i.e. valuing diverse ways of being and knowing)
      is what is needed in rehabilitation settings. When applied across cultures,
      ethnicity, gender, class and capability differences, these wiser ways of knowing
      can lead to more sustainable ways of being (i.e. what this author calls 'onto
      diversity for suss-tainability', playing on the modern slang term for 'sussing
      things out'--meaning gaining better understanding of what's really going on).

PMID- 19579130
TI  - Creative Recovery: art for mental health's sake.
AB  - OBJECTIVE: This paper describes the background to, implementation of and
      evaluation challenges associated with an innovative, arts-based, wellbeing and
      mental health recovery project in a remote Indigenous setting. RESULTS: Creative
      Recovery is a community-based arts initiative for Indigenous people with mental
      health problems. It has been rolled out as a pilot project in a remote Cape York
      community and is aimed at promoting wellbeing and recovery. The theoretical basis
      for the initiative is modelled on ideas of the role that social capital plays in
      improving mental health. This involves both the beneficial impact community
      participation and the social cohesion it creates can have, not only on an
      individual's mental health, but also on the social and emotional wellbeing of the
      communities they are part of. Such initiatives have already been adopted as an
      integral part of mental health promotion in countries such as the UK, and in
      other Australian states such as Victoria and Western Australia. The following
      paper will locate Creative Recovery in the current field of mental health
      promotion theory and Indigenous social and emotional wellbeing, and will discuss
      some of the evidence for and challenges inherent in adopting such initiatives.

PMID- 19579131
TI  - Art therapy: promoting wellbeing in rural and remote communities.
AB  - Art therapy encompasses both preventative and curative activities and aims to
      improve ways of engaging those who might be reticent in seeking more traditional
      forms of psychological support offered through 'talking therapies'. The Longreach
      base of the Royal Flying Doctor Service in Queensland provides mental health
      support to people living in rural and remote locations in central western
      Queensland and has been complemented since 2006 by the addition of a full-time
      art therapist. This paper provides an overview of art therapy and a description
      of this innovative approach to addressing mental health needs in a rural and
      remote setting.

PMID- 19579132
TI  - Pride and performance: evaluation challenges of a multimedia and information
      technologies project in remote Aboriginal Australia.
AB  - OBJECTIVES: This paper explores an approach to an evaluation challenge: to
      demonstrate the impact of an initiative drawing on innovative use of
      information/multimedia technology and performance to address perceived social
      needs within a disadvantaged, remote Indigenous Australian community. RESULTS:
      The approach is described and preliminary data are presented supporting the
      importance of local production and participation.

PMID- 19579133
TI  - Out of a digital chrysalis: NIHNMF (pronounced nymph--the National Indigenous
      Health and New Media Forum).
AB  - In conjunction with the Creating Futures conference, the inaugural meeting of the
      National Indigenous Health and New Media Forum (NIHNMF--pronounced as 'nymph')
      was held at the Tanks Gallery in Cairns, Queensland, Australia. This paper
      describes the background to this innovative meeting of media minds. It also
      explores an emerging vision for addressing Indigenous health disparities through
      digital inclusion to overcome the 'digital divide' between mainstream and
      Indigenous Australians that constrains the delivery of appropriate health
      promotion to this health priority population.

PMID- 19579134
TI  - Exploring new kinds of relationships using generative music-making software.
AB  - This project focuses upon the use of jam2jam, a generative computer system, to
      increase access to improvization experiences for children and to facilitate new
      kinds of relationships with artists. The network jamming system uses visual and
      audio cultural materials to enable communities to be expressive with artistic
      materials that they value as a community. As the system is part of a network,
      performances can be shared between communities at great distances and recordings
      of performances can be uploaded to a digital social network
      (http://www.jam2jam.com/) and shared both locally and with the wider community.
      This paper examines a preliminary project where artwork made by Indigenous mental
      health clients in Far North Queensland was digitized and given to a group of 8-12
      year-old urban Indigenous children to 'improvize' with and make music/video clips
      using the jam2jam instrument. It seeks to generate a discussion and identify
      applications within creative arts-led community health settings to facilitate new
      kinds of relationships with self, peers, local community, culture and artists
      through collaborative improvization.

PMID- 19579135
TI  - Poetry--recovery and beyond.
AB  - OBJECTIVE: The aim of this paper is to illustrate through poetry that self
      directed recovery from mental illness is possible, and that through vigilance and
      a supportive network of family and mental health workers, life beyond recovery
      can be full and rewarding for any consumer. CONCLUSIONS: Through positive choice,
      a consumer can break the cycle of admission and realize self-empowerment, which
      can lead to a full and complete life.

PMID- 19579137
TI  - A simple and efficient method for generating Nurr1-positive neuronal stem cells
      from human wisdom teeth (tNSC) and the potential of tNSC for stroke therapy.
AB  - BACKGROUND AIMS: We have isolated human neuronal stem cells from exfoliated third
      molars (wisdom teeth) using a simple and efficient method. The cultured neuronal
      stem cells (designated tNSC) expressed embryonic and adult stem cell markers,
      markers for chemotatic factor and its corresponding ligand, as well as neuron
      proteins. The tNSC expressed genes of Nurr1, NF-M and nestin. They were used to
      treat middle cerebral artery occlusion (MCAO) surgery-inflicted Sprague-Dawley
      (SD) rats to assess their therapeutic potential for stroke therapy. METHODS: For
      each tNSC cell line, a normal human impacted wisdom tooth was collected from a
      donor with consent. The tooth was cleaned thoroughly with normal saline. The
      molar was vigorously shaken or vortexed for 30 min in a 50-mL conical tube with
      15-20mL normal saline. The mixture of dental pulp was collected by centrifugation
      and cultured in a 25-cm(2) tissue culture flask with 4-5mL Medium 199
      supplemented with 5-10% fetal calf serum. The tNSC harvested from tissue culture,
      at a concentration of 1-2x10(5), were suspended in 3 microL saline solution and
      injected into the right dorsolateral striatum of experimental animals inflicted
      with MCAO. RESULTS: Behavioral measurements of the tNSC-treated SD rats showed a
      significant recovery from neurologic dysfunction after MCAO treatment. In
      contrast, a sham group of SD rats failed to recover from the surgery.
      Immunohistochemistry analysis of brain sections of the tNSC-treated SD rats
      showed survival of the transplanted cells. CONCLUSIONS: These results suggest
      that adult neuronal stem cells may be procured from third molars, and tNSC thus
      cultivated have potential for treatment of stroke-inflicted rats.

PMID- 19579138
TI  - Circulating TNFRI and TNFRII levels correlated with the disease activity score
      (DAS28) in rheumatoid arthritis.
AB  - OBJECTIVE: To measure levels of soluble tumour necrosis factor alpha (TNFalpha)
      receptor type I (sTNFRI) and type II (sTNFRII) in order to correlate them with C
      reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate
      (ESR), and disease activity score (DAS28) in RA patients. METHODS: We recruited
      41 RA patients classified according to American College of Rheumatology (ACR)
      criteria and 38 healthy subjects (HS). sTNFRI and sTNFRII were measured using an
      enzyme-linked immunosorbent assay (ELISA) kit. Clinical activity in RA patients
      was evaluated using the Disease Activity Score using 28 joint counts (DAS28). The
      statistical analysis was realized using SPSS version 10.0. RESULTS: Soluble TNFRI
      and TNFRII levels were higher in RA patients (p = 0.04 and 0.001, respectively)
      than HS. Serum levels of sTNFRI correlated with sTNFRII (r = 0.699, p < 0.0001).
      sTNFRII correlated with DAS28 (r = 0.375, p = 0.017), RF (r = 0.505, p = 0.004),
      and ESR (r = 0.323, p = 0.042). CONCLUSION: The increased levels of both sTNFRI
      and sTNFRII suggest a secondary event related to the inflammatory state observed
      in RA, whereas the correlation of sTNFRII with RF, ESR, and DAS28 reflects the
      preferential TNFRII shedding induced by TNFalpha. sTNFRII may be useful as an
      additional inflammatory marker in RA.

PMID- 19579139
TI  - Test-retest intra-rater reliability of vaginal measurement of pelvic floor muscle
      strength using Myomed 932.
AB  - OBJECTIVES: To investigate test-retest intra-rater reliability of measurements of
      pelvic floor muscle (PFM) strength using Myomed 932 (Enraf-Nonius, Delft, the
      Netherlands). DESIGN: Test-retest intra-rater reliability test with a 2-7 day
      interval. SETTING: Physiotherapy outpatient clinic in association with the
      Department of Physiotherapy, University of Iceland. POPULATION: Twenty healthy
      female volunteers in Reykjavik metropolitan area, Iceland, with a mean age of
      43.8 (SD 9.8) years, mean body mass index (BMI) 26.2 (SD 5.3), and mean parity
      2.1 children (SD 1.0). MAIN OUTCOME MEASURES: PFM strength during two attempts of
      maximal voluntary contraction (MVC) measured as vaginal squeeze pressure in
      hectoPascals (hPa). RESULTS: Mean MVC was 34.45 hPa (95% CI: 26.07-42.83) on Day
      1 and 34.05 hPa (95% CI: 26.66-41.44) on Day 2. The measurements ranged from 5-74
      hPa interindividually on Day 1 and 5-62 hPa on Day 2. Intraclass Correlation
      Coefficient (ICC) was 0.97; p < 0.001 and coefficient of variation (CV%) was
      11.09%. There was no significant difference between the first and second tests (p
      = 0.74). CONCLUSION: This test-retest intra-rater reliability study for Myomed
      932 showed a very good reliability using ICC. The CV%, however, indicated some
      degree of intra-individual variation. We suggest that this device can be used
      both in practice and clinical trials for assessing female PFM strength.

PMID- 19579140
TI  - The relation between urinary incontinence and steroid hormone levels in
      perimenopausal women. A report from the Women's Health in the Lund Area (WHILA)
      study.
AB  - OBJECTIVE: To outline possible associations between urinary incontinence (UI) and
      serum levels of steroid hormones in middle-aged women. DESIGN AND SETTING:
      Community-based observational study. SAMPLE: All women aged 50-59 living in the
      Lund area by December 1995 were invited to a screening procedure. Sixty-four
      percent (n = 6,917) attended the screening that included physical and laboratory
      examinations and questionnaires. METHODS: Serum levels of cortisol, testosterone,
      androstendione, SHBG (sex hormone-binding globulin), and estradiol were analyzed
      and the 2,221 (32%) women who reported urinary leakage causing a social or
      hygienic problem were compared to those who denied incontinence. MAIN OUTCOME
      MEASURE: Possible differences in serum levels of steroid hormones in continent
      and incontinent women. RESULTS: There were no significant differences between
      continent and incontinent women regarding serum levels of cortisol, testosterone,
      androstendione, or testosterone + androstendione combined. Serum estradiol
      adjusted for body mass index, parity, smoking, and hysterectomy was significantly
      higher in incontinent women (87.1 +/- 138.4 pmol/l vs. 78.0 +/- 118.5 pmol/l, p =
      0.005), whereas the ratio estradiol/SHBG was not. These differences persisted
      when the group of women not on hormonal treatment was analyzed. CONCLUSIONS: UI
      in middle-aged women seems related to higher serum estradiol levels. This
      corroborates with studies showing a higher incidence and/or prevalence of UI in
      women on hormone therapy. No association between UI and serum levels of cortisol,
      testosterone, or androstendione was found.

PMID- 19579141
TI  - Prevalence and incidence of dental caries and related risk factors in 70- to 76
      year-olds.
AB  - OBJECTIVE: The prevalence of caries and various risk factors was studied cross
      sectionally in two cohorts of 72-year-olds over the course of 20 years. Incidence
      was also studied over a period of 6 years. MATERIAL AND METHODS: Samples of two
      dentate subjects from cohorts of 70 to 72-year-olds were included; cohort III
      (n=135), born 1911-12, and cohort VI (n=139), born 1930. Cohort III was also
      examined at 70 years of age and re-examined after 6 years. An interview and
      clinical examination, including DMFS, plaque and gingival bleeding indices,
      pocket depth, and secretion rate for stimulated whole saliva, were carried out.
      RESULTS: The mean numbers of teeth in cohorts III and VI were 14 and 21,
      respectively. On average, 2.1 tooth surfaces were decayed (DS) in cohort III
      compared with 1.3 in cohort VI (p<0.05). 49% of the individuals in cohort III did
      not develop any new DS, while 19% developed >=3 DS during the 6-year follow-up
      period. The prevalence of caries was related to plaque and gingival bleeding
      indices, as well as a pocket depth of >=4 mm, at ages 70 and 72. Moreover, the
      incidence of caries was related to the same factors. CONCLUSIONS: The numbers of
      remaining teeth increased and the prevalence of caries decreased over the 20-year
      period. The incidence of caries over the follow-up period of 6 years was
      moderate. The results indicate that the prevalence of plaque, gingival bleeding,
      and a pocket depth of >=4 mm are predictive factors for both prevalence and
      incidence of caries.

PMID- 19579142
TI  - In vitro shear bond strength of dual-curing resin cements to two different high
      strength ceramic materials with different surface texture.
AB  - OBJECTIVE: The purpose of this study was to evaluate the shear bond strength
      (SBS) of two dual-curing resin cements to two high-strength ceramics with
      different surface texture. MATERIAL AND METHODS: Composite cylinders were bonded
      to aluminum oxide (A) and zirconium oxide (Z) ceramic disks with six different
      surfaces. Investigated surfaces were for both ceramics: dry-pressed Procera Crown
      (A1, Z1), machined Procera Bridge (A2, Z2), airborne particle abraded Procera
      bridge (A3, Z3). Additional surfaces were, for alumina, dry-pressed Procera
      Laminate (A4) and, for zirconia, two modified surfaces (Z4, Z5). Two adhesive
      resin cements were used (Clearfil Esthetic and RelyX ARC). SBS was tested in a
      universal testing machine before and after artificial aging by thermal cycling.
      RESULTS: Mean SBS ranged from 6.1 to 38.4 MPa before and from 0.0 to 41.4 MPa
      after aging. Clearfil Esthetic in A3, A4, and Z3 performed better than RelyX ARC.
      Aging decreased SBS, except for Z1, Z4, and Z5. For alumina, A4 was higher in SBS
      than A2, but similar to A1 and A3. For zirconia, Z5 showed the highest SBS. Z4
      was higher than Z2 and Z3, but similar to Z1. CONCLUSIONS: Shear bond strength to
      alumina and zirconia increases with surface roughness. The modified zirconia
      surface Z5 provides stable long-term shear bond strength and can be bonded to
      either of the two used cements.

PMID- 19579143
TI  - The value of scutum erosion in the diagnosis of temporal bone cholesteatoma.
AB  - CONCLUSIONS: Scutum erosion has an important role in the diagnosis of attic
      cholesteatoma, but it does not appear in other types of cholesteatoma in temporal
      bone. Without scutum erosion, the existence of cholesteatoma cannot be excluded.
      OBJECTIVE: To evaluate the value of scutum erosion in the diagnosis of
      cholesteatoma in temporal bone and its limitations. SUBJECTS AND METHODS: CT
      scanning and otoscopy were used in all patients who were suspected of developing,
      or were probably diagnosed with, cholesteatoma in temporal bone. The condition of
      the scutum was recorded by otoscopy, CT scanning and surgical findings in all
      patients with cholesteatomas. RESULTS: Scutum erosion can be shown in attic
      retraction with cholesteatoma at an early stage, but not in marginal perforation
      or with posterior retraction with cholesteatoma, or in central perforation or
      intact tympanic membrane with cholesteatoma, even in relatively late stages.

PMID- 19579144
TI  - Does vertigo disappear only by rolling over? Rehabilitation for benign paroxysmal
      positional vertigo.
AB  - CONCLUSION: We propose that the rolling-over maneuver (ROM) is as effective as
      the canalith repositioning maneuver (CRP) for the treatment of benign paroxysmal
      positional vertigo (BPPV). ROM involves easy movements, with only a small load.
      This therapy is suitable for most BPPV patients, even for those without an
      indication for CRP. OBJECTIVES: BPPV is a common vestibular disorder. CRP is
      known to be an effective therapy for the treatment of BPPV. Because of its
      various movements of the head and body, it is impossible to perform CRP in BPPV
      patients with orthopedic impairments or in the elderly. For these patients, we
      perform a maneuver called ROM, which involves easy movements. In this study, we
      compared the efficacy of ROM with that of CRP in patients with posterior
      semicircular canal-type BPPV. PATIENTS AND METHODS: The study included 22
      patients with BPPV who were randomized and divided into the following 2 groups:
      1) those treated by the modified Epley maneuver as CRP; and 2) those treated by
      ROM. RESULTS: We found no significant difference between the two groups in the
      number of days from onset to remission of both nystagmus and vertigo.

PMID- 19579146
TI  - Nuclear staining with alum hematoxylin.
AB  - The hematoxylin and eosin stain is the most common method used in anatomic
      pathology, yet it is a method about which technologists ask numerous questions.
      Hematoxylin is a natural dye obtained from a tree originally found in Central
      America, and is easily converted into the dye hematein. This dye forms
      coordination compounds with mordant metals, such as aluminum, and the resulting
      lake attaches to cell nuclei. Regressive formulations contain a higher
      concentration of dye than progressive formulations and may also contain a lower
      concentration of mordant. The presence of an acid increases the life of the
      solution and in progressive solutions may also affect selectivity of staining. An
      appendix lists more than 60 hemalum formulations and the ratio of dye to mordant
      for each.

PMID- 19579145
TI  - Mechanisms of hearing loss from trauma and inflammation: otoprotective therapies
      from the laboratory to the clinic.
AB  - This article reviews a series of in vitro and in vivo studies that examined the
      otoprotective efficacy of locally delivered dexamethasone and explored the
      mechanisms by which dexamethasone protects auditory hair cells. These studies
      used auditory threshold testing in response to pure tone stimuli, organ of Corti
      explant cultures, FITC-phalloidin-stained explants, and surface preparations to
      determine hair cell density, osmotic pump delivery of dexamethasone into the
      scala tympani, an animal model of electrode insertion trauma (EIT)-induced
      hearing loss, and real-time RT-PCR studies of gene expression levels. Local
      delivery of two different formulations of dexamethasone conserved hearing and
      protected hair cells in an animal model of cochlear implantation. Dexamethasone
      treatment protected hair cells in organ of Corti explants exposed to an ototoxic
      level of an inflammatory cytokine, and gene expression studies showed that this
      protection was accomplished by increased expression levels of anti-apoptosis
      genes (e.g. Bcl-2) and decreased levels of pro-apoptosis genes (e.g. Bax). We
      conclude that dexamethasone is an effective otoprotective drug for both the
      conservation of hearing and preservation of hair cells against trauma-induced
      losses. Locally delivered dexamethasone is a promising therapeutic approach for
      the conservation of hearing during the process of cochlear implantation.

PMID- 19579147
TI  - Feasibility of intravenous glucose tolerance testing prior to puberty.
AB  - OBJECTIVES: 1) Report the feasibility of completing the 180-minute Frequently
      Sampled Intravenous Glucose Tolerance Test (FSIVGTT) in healthy weight,
      overweight and obese pre-pubertal children and, 2) describe the finalized FSIVGTT
      protocol after addendums were implemented to decrease the frequency of mild
      adverse events and improve test completion rates. METHODS: Insulin sensitivity
      was determined by FSIVGTT. RESULTS: FSIVGTT was attempted in a total of 22 study
      participants. Insulin sensitivity was successfully assessed in 15 study
      participants (8 males, 7 females, 10 Caucasian, 4 African American, 1 Pacific
      Islander, age range 7-9 years). Mean insulin sensitivity was 15.1+/-9.8
      (mmicro/l)(-1) min(-1) range 4.4-43.2 (mmicro/l)(-1) min(-1). However, seven
      study participants experienced mild adverse events of hypoglycemia. Several
      addendums were made to the FSIVGTT protocol to ensure study participants' comfort
      and safety, and to decrease the frequency of mild adverse events and increase
      test completion rates. CONCLUSIONS: Addendums made to FSIVGTT protocol allowed
      successful completion of FSIVGTT in 15 (68%) of the 22 children. These results
      demonstrate that FSIVGTT is challenging, yet feasible in healthy lean and obese
      pre-pubertal children.

PMID- 19579148
TI  - Clinical and microbiological analysis of Elizabethkingia meningoseptica
      bacteremia in adult patients in Taiwan.
AB  - A limited number of reports have documented bacteremia caused by Elizabethkingia
      meningoseptica (Chryseobacterium meningosepticum) in adults. Most cases have
      occurred in Taiwan. This study investigated the clinical features and risk
      factors for mortality from E. meningoseptica bacteremia and the antimicrobial
      susceptibilities of the isolates. Patients with E. meningoseptica bacteremia were
      retrospectively analyzed at a medical center/teaching hospital in northern Taiwan
      over a 3-y period. We analyzed clinical features and outcomes of patients and
      antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE)
      results of the isolates. 28 patients had nosocomial bacteremia and 4 patients had
      healthcare associated bacteremia. The isolates exhibited variable
      susceptibilities to levofloxacin, ciprofloxacin, piperacillin-tazobactam,
      tigecycline, and trimethoprim-sulfamethoxazole. PFGE demonstrated that most
      isolates were epidemiologically unrelated. The 28-d mortality rate was 41%.
      Multivariate analysis indicated that shock and use of inappropriate antibiotics
      were independent risk factors for mortality. In conclusion, nosocomial
      bloodstream infection due to E. meningoseptica is an increasing problem in
      Taiwan. Our study indicates that patients with E. meningoseptica bacteremia face
      poor prognoses, with shock and use of inappropriate antibiotics as the main risk
      factors for mortality. Further clinical study is needed to establish the optimal
      therapy for E. meningoseptica bacteremia.

PMID- 19579149
TI  - Estimating the incidence, prevalence and clinical burden of hepatitis C over time
      in Italy.
AB  - Our objective was to estimate HCV clinical burden over time in Italy. A national
      age-specific HCV prevalence in 1995 was obtained from studies conducted in
      general population samples and intravenous drug users. Age profile of new HCV
      infections and trend of incidence since 1985 were derived from a database of
      reported acute HCV infections. These incidence and prevalence data were used to
      estimate HCV burden from 1950 to 2030 by mathematical modelling. Different rates
      of HCV related liver disease progression were tested to assess the robustness of
      estimates. It is estimated that HCV had a major spread in Italy in 1945-1969. HCV
      RNA-positive subjects peaked around 1970; their prevalence in 2005 was 3.2%, 58%
      of them being >65 y of age. The number of individuals with HCV related cirrhosis
      and that of HCV liver related deaths peaked in 1980-1985. In 2005, they were
      approximately 230,000 (range 150,000-240,000, according to lower or higher
      disease progression rates) and approximately 7,000 (range 2200-12,300),
      respectively: both will be halved by 2025. In conclusion, unlike other
      industrialized countries, the burden of clinically relevant HCV-positive cases in
      Italy is already on the decline and will further reduce in the future. This is
      due to differences in the age-specific prevalence, most of HCV-positive Italians
      currently being >65 y of age.

PMID- 19579150
TI  - Recurrent tonsillitis and tonsillectomy in juvenile idiopathic arthritis.
AB  - OBJECTIVES: To compare the clinical and bacteriological features of recurrent
      tonsillitis between patients with and without juvenile idiopathic arthritis
      (JIA). METHODS: A total of 122 participants, aged 2-18 years, were consecutively
      recruited into four groups: (i) JIA and recurrent tonsillitis; (ii) JIA; (iii)
      recurrent tonsillitis; and (iv) healthy. All the patients with recurrent
      tonsillitis underwent tonsillectomy. Swabs from tonsillar surface crypts of all
      children and samples from tonsillar core tissue in case of tonsillectomy were
      processed for culturing. Mycoplasma pneumoniae was determined by polymerase chain
      reaction (PCR). RESULTS: Significantly lower rates of recurrences but more
      frequent tonsillar detritus, paratonsillar scars, and more intensive bleeding
      during tonsillectomy were found in patients with JIA and recurrent tonsillitis,
      versus patients with recurrent tonsillitis without arthritis. In JIA patients
      with recurrent tonsillitis, Staphylococcus aureus was cultured from the tonsillar
      surface in 36%, and from the core tissue in 92% of cases (p = 0.0000). In
      patients suffering from recurrent tonsillitis alone, this pathogen was cultured
      from the core in 55.9% of cases (p = 0.0066 compared to JIA patients with
      recurrent tonsillitis). No M. pneumoniae was revealed by PCR in samples from the
      tonsillar surface and the core tissue. CONCLUSIONS: The increased rate of S.
      aureus in the core tissue of tonsils, the higher frequency of tonsillar detritus,
      the more pronounced paratonsillar scarring, and more intensive bleeding during
      tonsillectomy, associated with the lower frequency of tonsillitis recurrences,
      are characteristic for recurrent tonsillitis in JIA as compared to recurrent
      tonsillitis without arthritis.

PMID- 19579151
TI  - Immune-mediated skin lesions in patients treated with anti-tumour necrosis factor
      alpha inhibitors.
AB  - OBJECTIVE: To describe immune-mediated skin lesion (IMSL) development in patients
      during anti-tumour necrosis factor (TNF) therapy. METHODS: Two hundred and fifty
      two patients with rheumatoid arthritis (RA) and 183 with spondyloarthropathies
      (SpA) treated with anti-TNF inhibitors were analysed to identify IMSLs. RESULTS:
      Of the 252 patients with RA (146 treated with infliximab, 72 with adalimumab, and
      34 with etanercept), 32 developed IMSLs. Eleven patients developed psoriatic skin
      lesions, 10 presented with granuloma annulare (GA), five had skin vasculitis, two
      alopecia areata, two discoid lupus erythematosus, one lichenoid eruption (lichen
      planus), and one vitiligo. Of the 183 patients with SpA (138 treated with
      infliximab, 37 with etanercept, and eight with adalimumab), 10 cases with IMSLs
      were identified. All were treated with infliximab. More specifically, six
      patients with ankylosing spondylitis (AS) developed psoriatic skin lesions, one
      developed GA, one lichen planus, and one alopecia areata. In addition, one
      patient with psoriatic arthritis (PsA) developed skin vasculitis. The occurrence
      of these IMSLs ranged from 3 to 36 months with a median of 20 months. Of all the
      patients with IMSL development, two with psoriatic skin lesions, two with GA, and
      one with vasculitis stopped anti-TNF therapy because of the extent and severity
      of the skin lesions. CONCLUSIONS: Our results on patients treated with TNF
      antagonists strongly support a link between TNF inhibition and IMSL development.
      Although these clinical complications are rare, clinicians should be aware of
      their occurrence and should recognize them.

PMID- 19579152
TI  - Low back pain and determinants of sickness absence.
AB  - BACKGROUND: Low back pain (LBP) is a frequent diagnosis for sickness absence. The
      process of sick-listing is complex, and the doctor must integrate information
      from several levels in the decision. OBJECTIVE: The aim of this paper is to
      describe the main determinants of sickness absence for LBP. METHODS: We conducted
      a non-systematic search in Medline and personal files to identify determinants of
      sickness absence, and structured these into four levels of the sick-listing
      process. These levels are characteristics of 1) the sick-listed worker, 2) the
      sick-listing doctor, 3) the workplace, and 4) the cultural and economic
      conditions of the society. RESULTS: Important characteristics of the sick-listed
      person seem to be poor mental health, including negative beliefs about LBP. Also,
      comorbidity and lack of coping abilities are found associated to sickness
      absence. The impact of the doctors' personal beliefs about LBP is not clear.
      Doctors in general seem to be frustrated by their gatekeeper role and the
      influence of other healthcare providers on the sick-listing decision. The
      workplace is an important factor in the sick-listing process, but the impact of
      physical working conditions is of less importance than social support, job
      control, and demands. On the society level, the economic awards in sickness
      absence and the general acceptance of being sick listed seem to be of importance
      for the individual's decision to claim sick leave. CONCLUSION: The sick-listing
      process for LBP is complex, and the determinants are mostly non-medical. It seems
      important to adopt a broad perspective of how a worker copes with pain and how
      these coping strategies interact with cultural, economic, and societal
      determinants of sickness certification.

PMID- 19579153
TI  - The relation between care giving and the mental health of caregivers of demented
      relatives: a cross-sectional study.
AB  - BACKGROUND: Increasing numbers of family caregivers are confronted with caring
      for a demented, community-dwelling relative. Living with, caring for, and
      supervising a demented older relative places a heavy burden on the involved
      family members. In particular, primary caregivers report increased strain,
      feelings of depression, and decreased general wellbeing as a direct consequence
      of care giving. Since the most common cause of failure of a home-care situation
      appears to be caregiver burnout, detecting critical, negative changes in the
      wellbeing of the caregiver is important. METHODS: In a nationwide, cross
      sectional study by the Belgium Social Security Board, a population of demented
      older patients and their care-giving relatives was investigated. The care
      situation and characteristics of demented, older patients and their caregivers
      were inventoried, and their effects on the wellbeing of caregivers were
      evaluated. RESULTS: Approximately 30% (n = 28) of caregivers of demented, older
      relatives were depressed. Depression occurred independently of objective care
      characteristics and the mental and physical state of the demented patient.
      Rather, it was related to coping mechanisms and to the perceived burden reported
      by the caregiver. CONCLUSION: Offering support and counsel to caregivers is an
      important issue in efficiently maintaining home-care situations.

PMID- 19579154
TI  - American society of clinical oncology - 45th annual meeting. Part 1.

PMID- 19579155
TI  - American society of clinical oncology - 45th annual meeting. Part 2.

PMID- 19579156
TI  - International society for antiviral research - 22nd international conference.
      Part 1.

PMID- 19579157
TI  - International society for antiviral research - 22nd international conference.
      Part 2.

PMID- 19579158
TI  - Association for research in vision and ophthalmology - 2009 annual meeting.
      Reducing disparities in eye disease and treatment: part 1.

PMID- 19579159
TI  - Association for research in vision and ophthalmology - 2009 annual meeting.
      Reducing disparities in eye disease and treatment: part 2.

PMID- 19579160
TI  - Clinical Microbiology and Infectious Diseases - 19th European Congress. New
      antimicrobials against resistant Staphylococcus aureus.

PMID- 19579161
TI  - International society for the study of xenobiotics - 11th European meeting.

PMID- 19579162
TI  - Translational biomarkers for accelerating drug development: From preclinical to
      clinical - AAPS Workshop.

PMID- 19579163
TI  - World stem cells & regenerative medicine - Terrapinn's Fourth Annual Congress.

PMID- 19579164
TI  - HIV vaccine development: Lessons from the past, informing the future.
AB  - In September 2007, a clinical trial (STEP trial) evaluating the candidate HIV
      vaccine MRK Ad5 HIV-1 gag/pol/nef from Merck & Co Inc was halted at the first
      interim analysis because the vaccine demonstrated no positive impact on virus
      acquisition or virus load following infection. Additionally, there was an
      increased rate of HIV infection in vaccinees who had prior immunity to adenovirus
      type 5 (Ad5) and/or were circumcised. This failure of the vaccine, as well as the
      apparent harm caused to some study participants, generated a massive pessimism
      regarding HIV vaccine development. Concerns regarding the future of HIV vaccine
      research led to a summit convened by the NIAID in March 2008 to provide new
      directions in HIV vaccine research. A shift in emphasis focused on three areas:
      discovery research, animal models and clinical research. In each of these areas,
      notable new activities have occurred: a wealth of information has emerged from
      the STEP trial, promising results have been reported on assay development for
      markers of vaccine-induced immune function, and evaluations of promising new
      experimental vaccines have occurred in nonhuman primates. Overall, the progress
      in the field of HIV vaccine research since September 2007 has reinforced the need
      for a balanced approach between basic vaccine discovery and development, as well
      as the importance of addressing questions in nonhuman primate studies and
      clinical trials. This article discusses how past product failures have
      invigorated the field of HIV vaccine research by addressing critical questions
      and suggesting additional possible approaches to follow. As a result of the
      insight gained, a new sense of optimism exists in the field of HIV vaccine
      research.

PMID- 19579165
TI  - The challenges of immunogenicity in developing biosimilar products.
AB  - Unwanted immunogenicity is a significant issue affecting most biotherapeutic
      products, including subsequent entry biological (SEB) medicines. Such
      immunogenicity can be associated with adverse reactions and can cause impaired
      clinical responses to the biotherapeutic. This feature article provides an
      overview of the challenges facing the biotechnology industry with regard to the
      prediction and assessment of immunogenicity of SEBs and, in particular,
      biosimilar products. In addition, the available guidance on assessing the
      immunogenicity of biotherapeutic products is discussed.

PMID- 19579166
TI  - Trabedersen, a TGFbeta2-specific antisense oligonucleotide for the treatment of
      malignant gliomas and other tumors overexpressing TGFbeta2.
AB  - Trabedersen (AP-12009), which is being developed by Antisense Pharma GmbH, is a
      synthetic antisense oligodeoxynucleotide designed to block the production of
      TGFbeta2, a secreted protein that can exert protumor effects. Trabedersen is
      indicated for the treatment of malignant brain tumors and other solid tumors
      overexpressing TGFbeta2, such as those of the skin, pancreas and colon.
      Preclinical studies demonstrated that trabedersen reduced the secretion of
      TGFbeta2 in cultured tumor cells and exhibited antitumor activity ex vivo. It was
      also demonstrated that chronic intracerebral or intravascular administration of
      trabedersen did not cause life-threatening side effects in animals. This
      observation was confirmed in early clinical trials in patients with advanced
      cancer. In a phase IIb trial, improved survival was observed in patients with
      brain tumors who were intratumorally administered trabedersen, compared with
      patients receiving standard chemotherapy. However, this observation requires
      validation by an ongoing large-scale, phase III, randomized, controlled trial.
      Meanwhile, continued research on trabedersen should help to determine the roles
      of TGFbeta2 in cancer and also further the development of antisense technology.

PMID- 19579167
TI  - Let's get some structure into neuroscience drug discovery.

PMID- 19579168
TI  - Vascular cognitive impairment: dementia biology and translational animal models.
AB  - Relationships between cardiovascular risk and disease, and dementia have been
      identified, and the term vascular cognitive impairment (VCI) is used to describe
      individuals with significant cognitive impairments produced by cerebrovascular
      disease (CVD). VCI is the second most prevalent form of dementia and is composed
      of a heterogeneous pathology. Risk factors for VCI are similar to those of the
      most prevalent form of dementia, Alzheimer's disease (AD). In addition, recent
      data suggest that VCI can contribute significantly to the progression of AD, and
      AD can contribute to VCI. Translational animal models of VCI are necessary to
      further understand CVD mechanisms contributing to impaired cognition. This review
      describes animal models of cerebrovascular insufficiency (ie, chronic
      hypoperfusion and hypertension) that produce experimental VCI, including their
      relationships to human VCI and, when appropriate, to AD. The use of these models
      is expected to help discover biomarkers and disease mechanism-linked targets for
      diagnostic and therapeutic purposes, thus facilitating early identification and
      intervention in VCI.

PMID- 19579169
TI  - The role of IL-2 and soluble IL-2R in depression and antidepressant response.
AB  - Cytokines are widely studied in the context of the pathogenesis and treatment of
      major depression. This review focuses on the potential importance of IL-2 and
      soluble IL-2R in major depression, as well as on their role in the mediation of
      the effects of antidepressant treatment. In general, there has been no consistent
      pattern in the associations observed between cytokine concentration, or changes
      thereof, and clinical indices of major depression. One intriguing question is
      whether pretreatment levels of immune system markers, such as IL-2R alpha, can be
      used to predict responses to antidepressant treatment. Based on the currently
      available data, this issue remains unresolved. This review also highlights
      certain methodological problems pertaining to the measurement of IL-2 and IL-2R
      in the context of depression and presents ideas for further research in this
      field.

PMID- 19579170
TI  - Injury and repair mechanisms in ischemic stroke: considerations for the
      development of novel neurotherapeutics.
AB  - Ischemic stroke triggers a complex and highly interconnected cascade of cellular
      and molecular events. Early events induced following ischemic injury, including
      excitotoxicity, calcium overload and oxidative stress, rapidly result in cell
      death in the infarct core. Later events, such as neuroinflammation and apoptosis,
      are relevant to the death of the ischemic penumbra. Drugs that limit delayed
      injury events have a wide therapeutic window for protection; however, the
      damaging events of the ischemic cascade will eventually prevail if reperfusion is
      not achieved within minutes after ischemia. The combination of thrombolytics with
      protective drugs may provide a promising therapy in the management of stroke.
      Targeting all components of the neurovascular unit, rather than just the neuron,
      should be a priority in stroke research, and agents that block multiple events of
      the injury cascade are more likely to provide cerebroprotection. Understanding
      when the brain begins the transition from injury to repair could have important
      implications for stroke therapy. Several ischemic mediators have dual roles, with
      detrimental acute effects, but beneficial effects in the repair phase; therefore,
      extending experimental stroke investigations to an analysis of the long-term
      outcome is important. This review provides a critical evaluation of promising
      therapeutic strategies for ischemic stroke, and a translational perspective on
      how to improve success in the development of novel pharmaceuticals for cerebral
      ischemia.

PMID- 19579171
TI  - TRP channel antagonists for pain--opportunities beyond TRPV1.
AB  - There is emerging evidence that transient receptor potential (TRP) ion channels
      expressed in sensory neurons are important for the transduction of chemical,
      thermal and mechanical signals. Increasing research efforts are directed at
      understanding the roles of sensory TRP channels in acute and chronic pain.
      Studies using RNAi techniques to reduce the levels of individual TRP channels or
      genetically modified mice lacking specific channels are being complemented with
      pharmacological studies using newly discovered investigational compounds. These
      studies are providing evidence that drugs that interfere with the function of
      TRPA1, TRPM8, TRPV4 or TRPV3 may be useful in treating pain.

PMID- 19579173
TI  - The role of RAGE in amyloid-beta peptide-mediated pathology in Alzheimer's
      disease.
AB  - This review discusses current knowledge of the complex interactions between
      amyloid-beta (A beta) peptide, the receptor for advanced glycation endproducts
      (RAGE), and inflammatory mediators, focusing on the roles of such interactions in
      the pathogenesis of Alzheimer's disease. As a ubiquitous cell-surface receptor,
      RAGE demonstrates enhanced expression in an A beta-rich environment; the effects
      of RAGE on microglia, the blood-brain barrier and neurons are mediated through
      various signaling pathways. Relevant preclinical models illustrate that the A
      beta-RAGE interaction amplifies neuronal stress and the accumulation of A beta,
      impairs memory and learning, and exaggerates neuroinflammation. These findings
      suggest that RAGE may mediate a common proinflammatory pathway in
      neurodegenerative disorders.

PMID- 19579174
TI  - Central regulation of ejaculation and the therapeutic role of serotonergic agents
      in premature ejaculation.
AB  - Premature ejaculation (PE) is characterized by a short ejaculatory latency time,
      poor control over ejaculation and a negative impact on quality of life. The
      process of ejaculation is under central control, and serotonin (5-HT) is a key
      mediator; therefore, SSRIs and tricyclic antidepressants, including paroxetine,
      sertraline and clomipramine, are commonly used with chronic daily dosing in the
      treatment of PE. Dapoxetine, a short-acting SSRI that acts supraspinally to
      inhibit ejaculation, has been approved in several European countries for on
      demand treatment of PE. With a range of centrally acting treatment options,
      treatment should be tailored to meet the needs and preferences of individual
      patients.

PMID- 19579172
TI  - Evidence for IL-1 receptor blockade as a therapeutic strategy for the treatment
      of depression.
AB  - Uncontrollable stress, a major precipitant of depression in humans and in animal
      paradigms, impairs hippocampal neurogenesis, which is necessary for the
      behavioral effects of antidepressants in models of depression that require
      chronic treatment. However, the mechanisms underlying these anti-neurogenic and
      behavioral effects of stress have not been elucidated. Proinflammatory cytokines
      are thought to be contributing factors to stress and have been implicated in
      stress-related mood disorders such as major depression. In particular, IL-1 beta
      has been proposed to be a key mediator in a variety of behavioral actions of
      stress. Notably, the administration of a IL-1 receptor antagonist (IL-1Ra) blocks
      the stress-like effects of IL-1 beta in both cellular and behavioral models. This
      review highlights the increasing interest in the relationship between IL-1 beta,
      neurogenesis, stress and depression, and discusses the potential of IL-1Ra or
      other cytokine antagonists as new candidates for the treatment of depression.

PMID- 19579175
TI  - Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian
      rhythm sleep disorders.
AB  - Tasimelteon, developed by Vanda Pharmaceuticals Inc under license from Bristol
      Myers Squibb Co, is a melatonin receptor agonist. Because of the high density of
      melatonin receptors in the circadian pacemaker, the suprachiasmatic nucleus,
      melatonergic actions can phase-shift circadian rhythms and promote sleep.
      Tasimelteon was effective in reducing sleep onset latency (in phase II and III
      clinical trials) and in resetting the circadian melatonin rhythm (in phase II
      trials), which indicated its potential suitability as treatment for jet lag,
      shift work and circadian rhythm sleep disorders. Statistically significant
      improvements in sleep maintenance have also been observed with the drug.
      Tasimelteon has been claimed to be useful in the treatment of depression, and
      preclinical evidence in this respect is to be confirmed in a phase II clinical
      trial, which was ready to be initiated at the time of publication. It is
      plausible that the drug may be effective in the treatment of depressive
      disorders, at least those that are related to circadian dysfunction, and that it
      may attenuate sleep problems in depressed patients of different subtypes. A
      general suitability in mitigating other symptoms of major depressive disorder
      cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1
      and MT2. The drug is well tolerated, does not induce impairment of next-day
      functioning or dependence, and seems to be safe in short-term treatment; however,
      toxicological data would be required for assessing its long-term safety.

PMID- 19579176
TI  - NGX-4010, a high-concentration capsaicin dermal patch for lasting relief of
      peripheral neuropathic pain.
AB  - NeurogesX Inc is developing NGX-4010, a rapid-delivery dermal patch application
      system that contains high-concentration trans-capsaicin, for the treatment of
      peripheral neuropathic pain. Capsaicin evokes a lasting and reversible refractory
      state in primary sensory neurons involved in the generation and maintenance of
      neuropathic pain. NGX-4010 can be applied to the painful skin area up to a total
      surface area of 1120 cm2. In phase I clinical trials, NGX-4010 increased the
      threshold for warmth detection, reduced epidermal sensory nerve fiber density and
      was well tolerated. In phase II trials, NGX-4010 was effective in reducing pain
      in patients with post-herpetic neuralgia (PHN), HIV-associated distal sensory
      neuropathy (HIV-DSP) and painful diabetic neuropathy (PDN). Data from phase III
      trials in patients with PHN demonstrated that significantly more pain relief was
      achieved by NGX-4010 (30 to 32% reduction from baseline) compared with a low
      concentration capsaicin active control (20 to 24% reduction); however, only one
      of two studies involving patients with HIV-DSP met the primary endpoint. NGX-4010
      appears to have the potential to be an effective adjunctive or a stand-alone
      therapy for PHN, as well as potentially for HIV-DSP and PDN. NGX-4010 has been
      granted approval by the European Commission and an NDA has been accepted for
      filing by the FDA.

PMID- 19579177
TI  - Telcagepant, a calcitonin gene-related peptide antagonist for the treatment of
      migraine.
AB  - Telcagepant is an oral calcitonin-gene related peptide (CGRP) receptor antagonist
      that is being developed by Merck & Co Inc for the treatment of migraine. This
      compound blocks CGRP receptors and may block the dilation of dural vessels and
      reduce neurotransmission in the CNS, resulting in pain relief. Telcagepant does
      not cause vasoconstriction, one of the major limitations in the use of triptans,
      which are considered to be the standard of care for migraine. Data from phase II
      and III clinical trials suggest that the use of telcagepant for the acute
      treatment of migraine was comparable with the use of triptan compounds and was
      superior to placebo in all primary endpoints, including pain relief and freedom
      from pain at 2 h. However, recent data reported elevated transaminase levels when
      telcagepant was dosed daily rather than acutely. It was concluded that, if these
      hepatic toxicities are not observed in ongoing/future trials of the acute use of
      telcagepant, then this agent may offer an alternative to triptan therapy for the
      treatment of migraine.

PMID- 19579178
TI  - Semagacestat, a gamma-secretase inhibitor for the potential treatment of
      Alzheimer's disease.
AB  - Eli Lilly & Co is developing semagacestat, an inhibitor of the gamma-secretase
      enzyme. This enzyme is pivotal in the generation of beta-amyloid (A beta), a
      neurotoxic endogenous peptide believed to be involved in the pathogenesis of
      Alzheimer's disease (AD). In animals, semagacestat reduced A beta levels in the
      plasma, CSF and brain; however, studies have not reported on cognitive effect of
      this compound. Phase I clinical trials in healthy volunteers have evaluated doses
      ranging from 5 to 140 mg/day and phase II trials in patients with AD have
      evaluated doses ranging from 30 to 140 mg/day for up to 14 weeks. Trials in both
      healthy volunteers and patients with AD have demonstrated a dose-dependent
      inhibition of plasma A beta levels, and a recent trial in healthy volunteers
      demonstrated a robust, dose-dependent inhibition of newly generated A beta in the
      CSF after single oral doses. The main adverse events involved the
      gastrointestinal tract. In 2008, two large phase III clinical trials in patients
      with mild-to-moderate AD were initiated by Eli Lilly. Semagacestat is the most
      advanced gamma-secretase inhibitor and represents a major hope among therapies
      designed to slow the rate of cognitive decline of patients with AD.

PMID- 19579179
TI  - Inhibition of neutral endopeptidase 24.11 does not potentiate the improvement in
      glycemic control obtained with dipeptidyl peptidase-4 inhibition in diabetic Goto
      Kakizaki rats.

PMID- 19579180
TI  - Regulation of glucose-6-phosphatase gene expression by insulin and metformin.
AB  - The biguanide derivative metformin is a potent anti-diabetic drug widely used in
      the treatment of type 2 diabetes mellitus. Its major effect on glucose metabolism
      consists in the inhibition of hepatic glucose production. Since the mechanisms of
      metformin action are only partially understood at the molecular level, we studied
      the regulation of the gene promoter activity of glucose-6-phosphatase (G6Pase),
      the central hepatic gluconeogenic enzyme, by this drug. We have found that both
      metformin and insulin inhibit the basal and dexamethasone/cAMP-stimulated G6Pase
      promoter activity in hepatoma cells. Since one of the pharmacological targets of
      metformin is AMP-activated protein kinase (AMPK) and activation of AMPK is known
      to inhibit hepatic glucose production by the suppression of G6Pase gene
      transcription, we studied the effect of AMPK in this context. Under nonstimulated
      conditions, the inhibitory effect of both insulin and metformin was partially
      counteracted to a similar extent by treatment with compound C, a specific
      inhibitor of AMPK. In contrast, under conditions of stimulation with
      dexamethasone and cAMP, treatment with compound C reversed the inhibitory effect
      of metformin on G6Pase promoter activity to a similar extent as compared to
      nonstimulated conditions, whereas the effect of insulin was almost resistant to
      treatment with the AMPK-antagonist. These data indicate a differential AMPK
      dependent regulation of G6Pase gene expression by insulin and metformin under
      basal and dexamethasone/cAMP-stimulated conditions.

PMID- 19579181
TI  - Escin, a natural mixture of triterpene saponins, exhibits antitumor activity
      against hepatocellular carcinoma.
AB  - Escin, a mixture of triterpene saponins extracted from Aesculus wilsonii Rehd.,
      was used to analyze the antitumor effect in hepatocellular carcinoma in vivo and
      in vitro. At a dose of 2.8 mg/kg, escin had a rather high inhibition ratio (43.5
      %) on mice H22 tumor growth in vivo. The results of the SRB cell viability assay
      showed that escin could induce significant concentration- and time-dependent
      inhibition of HepG (2) cell viability. Disruption of the G (1)/S phase of cell
      cycle progression accompanied by the induction of apoptosis were also observed in
      HepG (2) cells following escin treatment. The results of pulse-field gel
      electrophoresis and Western blot analysis show the induction of caspase
      independent apoptosis by escin. This study provides evidence that escin induces
      cell cycle checkpoint arrest and caspase-independent cell death in HepG (2)
      cells, in support of its efficacious potential as a chemopreventive agent.

PMID- 19579182
TI  - Antioxidative phenylpropanoid-substituted epicatechin glycosides from Parabarium
      huaitingii.
AB  - Three new phenylpropanoid-substituted epicatechin glycosides, namely
      parabarosides A - C ( 1- 3), together with three known compounds, 5
      caffeoylquinic acid (4), 5-caffeoylshikimic acid (5), and 3,4-dicaffeoylquinic
      acid (6), were obtained from the plant Parabarium huaitingii. Their structures
      were determined and full assignments of (1)H- and (13)C-NMR spectroscopic data
      were achieved by analyses of 1D- and 2D-NMR, mass, and CD spectra. The oxygen
      radical absorbance capacity (ORAC) assay was applied to evaluate their
      antioxidative capacity in vitro, which revealed that 1- 6 showed strong
      antioxidative properties.

PMID- 19579183
TI  - cis-Clerodane diterpenoids from the liverwort Gottschelia schizopleura and their
      cytotoxic activity.
AB  - Two new and three previously known CIS-clerodane diterpenoids were isolated from
      the wild liverwort Gottschelia schizopleura (Jungermanniales, Jungermanniaceae).
      Their structures were established on the basis of spectroscopic analysis,
      especially 1D and 2D NMR data. The cytotoxic activities of compounds 1- 5 were
      evaluated against liver hepatoblastoma (HEP-G2), lung carcinoma (A549), breast
      ductal carcinoma (MDA-MB-435), and colon adenocarcinoma (LOVO) cell lines.
      Compound 1 showed moderate inhibition against MDA-MB-435 and LOVO cells.

PMID- 19579184
TI  - Chemical constituents of Dracocephalum forrestii.
AB  - A systematic phytochemical examination of the whole plant Dracocephalum forrestii
      led to the isolation of 4 new and 65 known chemical constituents. By detailed 1D
      and 2D NMR spectroscopic analyses, the new compounds were identified as 4-hydroxy
      3-methoxyphenylethanol 8- O-[(6- O-syringoyl)- beta- D-glucopyranoside] (1),
      3,4,5-trimethoxyphenylethanol beta- D-glucopyranoside ( 2), 4- O-[ beta- D
      glucopyranosyl-(1 --> 3)- alpha- L-rhamnopyranosyl]phenylethylcinnamamide (3),
      and 9''- O- N-butyl lithospermate (4). The new isolates were evaluated for
      inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages.
      Compound 2 revealed a moderate effect without any cytotoxicity under the assayed
      concentrations.

PMID- 19579185
TI  - In vitro anticancer potential of tree extracts from the Walloon Region forest.
AB  - Forty-eight extracts from 16 common Belgian trees from the Walloon Region forest
      were evaluated for in vitro growth inhibitory activity against the human LoVo
      colon cancer, PC3 prostate cancer, and U373 glioblastoma cell lines. Our study
      was performed with the aim of selecting plant candidates in order to later
      isolate new anticancer compounds from an easily affordable tree material.
      Extracts from Alnus glutinosa (stem bark), Carpinus betulus (leaves and stem
      bark), Castanea sativa (stem bark), Fagus sylvatica (leaves), Ilex aquifolium
      (leaves), Larix decidua (leaves), Quercus petraea (stem bark), and Quercus robur
      (leaves) showed for the first time potent in vitro growth inhibitory activity and
      could become easily affordable sources of potential new anticancer agents. Root
      extracts from Robinia pseudoacacia, already known for containing cytotoxic
      lectins, also showed interesting activity.

PMID- 19579186
TI  - Single Port Access (SPATM) Minimal Access Surgery Through a Single Incision.
AB  - The practice of surgical techniques is constantly improving and evolving. In the
      last two decades, minimally invasive surgery has gained widespread acceptance.
      Virtually all procedures can now be performed laparoscopically. This trend not
      only provides better cosmesis, but offers decreased recovery times as well. The
      initial trend from open to laparoscopic surgery was to use smaller incisions. The
      natural continuation of this is to now decrease the number of incisions necessary
      to perform minimal access surgery. To this end, the authors have seen a
      constantly evolving stream of technology and instrumentation in laparoscopy. New
      venues, such as robotics and Natural Orifice. Transluminal Endoscopic Surgery
      (NOTES), have developed as well. As part of this evolution, the authors developed
      Single Port Access (SPATM) surgery in April 2007 as a novel and innovative
      platform of minimal access surgery. Its acceptance through our training programs,
      as well as the subsequent development of modified Single Port techniques,
      demonstrates the potential to develop a new platform of minimal access surgery.
      The SPATM technique is a method of abdominal entry for a wide spectrum of
      laparoscopic procedures performed by multiple surgical specialties. Using the
      access techniques we developed, the authors have performed nearly 200 general
      surgical and gynecologic procedures through a single incision, often <2 cm in
      length and hidden within the umbilicus. In addition, the development of SPATM
      surgery has been focused on using current and standard instrumentation, as well
      as currently practiced surgical techniques already familiar to surgeons in
      standard multiport laparoscopy. The "Independence of Motion" attained in this
      access technique, without the need for any new access or operative devices,
      allows up to four instruments to be place through a single incision<2 cm in
      length. We have striven to maintain safety principles of multiport laparoscopy,
      as well, and have continued to improve the technique to increase the availability
      and broad application of SPATM surgery. Out technique and its application, across
      a broad range of surgical procedures and surgical specialties, are presented
      herein.

PMID- 19579187
TI  - Notes: technical aspects - hype or hope?
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is currently an intensely
      discussed topic. The debate is extremely controversial, ranging from euphoric
      visions to complete refusal, and the future clinical role of natural orifice
      surgery is difficult to describe. This chapter analyzes the current technological
      status, and addresses the question of whether to enrich the surgical procedures
      will become an option. A literature research was undertaken using Medline and
      Pubmed. Personal experiences and communications were also included in this state
      of-the-art report. The individual barriers currently impeding the clinical use,
      as defined by the NOSCAR group, are addressed in detail. With the exception of
      the vaginal access, no natural orifice-entering technique is already clinically
      mature. The selective use-potentially in combination-in a more refined technique
      than currently, is likely to provide a breakthrough. Most of the remaining
      obstacles are just a matter of further progress in advanced medical engineering.
      However, it should not be forgotten that the problems to be solved are less than
      trivial, and close cooperation between engineers and surgeons is essential. NOTES
      is still in the early stages of development. Currently available tools and
      techniques remain in the pioneer stage. However, worldwide activities in research
      and development will lead to promising solutions, which certainly will help to
      overcome the existing barriers. Whether "pure NOTES" or hybrid procedures only,
      surgery will take another step forward toward a less-invasive discipline.

PMID- 19579188
TI  - Automation in surgery: a systematic approach.
AB  - This chapter proposes a classification of surgical assistance systems with
      respect to their type and level of automation. This classification is based on
      previous work in the field of human factors and takes two aspects into
      consideration, the type of information-processing function of the surgeon that is
      supported by the system, as well as the type of function allocation between
      surgeon and systems. With respect to the former, three basic functions are
      distinguished, referred to as information acquisition and analysis, decision
      making and planning, and execution of surgical action. With respect to the type
      of function allocation, the status of being either "passive" or "active" comes
      into consideration for both objects of reference (i.e. the surgeon and the
      machine), depending on whether a given function is mainly performed by the
      surgeon, by the system, or collaboratively by both. Hence, a classification
      results for intraoperative assistance systems in six categories, each of these
      representing a different degree of automation. The classification scheme is
      explained and illustrated on the basis of examples of surgical assistance systems
      from various fields.

PMID- 19579189
TI  - Novel propylene oxide-treated bovine pericardium as soft tissue repair material
      and potential scaffold for tissue engineering.
AB  - In contrast with autographic or allographic repair materials, the use of a
      xenographic soft tissue repair material could improve patient outcomes following
      surgery, since such a material would not require a second surgical site and could
      reduce the risk of human-to-human disease transmission. Veritas(c) Collagen
      Matrix (Veritas) is a novel, non-crosslinked soft tissue repair material derived
      from bovine pericardium. Physical property testing shows this material is strong,
      malleable, of uniform thickness, and easily sutureable. Biocompatibility testing,
      as well as viral safety and extractable deoxyribonucleic acid (DNA) studies
      demonstrate the acellularity, safety, and immunological inertness of the
      material. Animal studies in pigs and rabbits, in a variety of surgical procedures
      that include abdominal wall implant, unilateral hysterectomy, urethral sling
      implant, and dural substitute studies demonstrate Veritas does not adhere readily
      to tissues of the chest wall or abdomen under conditions that promote adhesions.
      In addition, these studies show that Veritas is remodelable and, in time, becomes
      histologically indistinguishable from the host tissue. These findings indicate
      Veritas is an ideal soft tissue repair material and it may serve as an ideal
      scaffold for tissue engineering.

PMID- 19579190
TI  - Neurosurgical applications of laser technology.
AB  - Although lasers have been used in clinical neurosurgery for over 40 years,
      technological advancements have expanded their use and improved technical
      application. Originally applied to brain tumors to confer destructive oncolysis,
      lasers have been used over the last few decades to incise, fenestrate, and repair
      tissues and now are being used for cerebrovascular bypass techniques. In this
      chapter, a brief history on the evolution of lasers in neurosurgery will be
      discussed, and technical and clinical aspects of current applications will
      presented. Such applications include: laser scalpel for spinal cord tumors and
      lipomas, fenestration of arachnoid cysts, cerebrovascular bypass with the ELANA
      device, laser-induced interstitial thermotherapy for brain tumors, laser tissue
      soldering for dural repair, and percutaneous laser disc decompression.

PMID- 19579191
TI  - Robotic laparoscopic surgery with the da Vinci(r) system: an early experience.
AB  - Theoretically, robotic surgery is likely to overcome the intrinsic limitations of
      laparoscopic surgery, such as a view not under the direct surgeon's control, two
      dimensional imaging, and limited motion of instruments. In this chapter, the
      preliminary experience with a robotic laparoscopic surgery system in the Surgical
      Department of the Alessandria Hospital, Italy, is reported. From November 2005 to
      August 2007, a total of 162 laparoscopic robotic operations were performed, in
      which robotic surgery was found to be feasible and safe. It takes a longer time
      than standard laparoscopy but seems able to reduce the need of a steep learning
      curve.

PMID- 19579192
TI  - Use of oxidized cellulose hemostats (SurgicelTM) to support parenchymal closure
      and achieve hemostasis following partial nephrectomy.
AB  - Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) has gained
      general acceptance as an alternative to radical nephrectomy. To achieve
      hemostasis without risk of local ischemia and necrosis of kidney parenchyma after
      standard hemostatic suturing, we investigated oxidized cellulose hemostats'
      efficacy and safety as atraumatic hemostatic treatment and for the closure of a
      large parenchymal defect after kidney tumor resection. Our approach has been
      particularly helpful for repairing large and irregular renal parenchymal defects.
      This study demonstrates the use of oxidized cellulose hemostats is effective for
      rapid, hemostatic closure of the kidney in association with partial nephrectomy.

PMID- 19579193
TI  - Implementing the general use of dissection devices in thyroid surgery from
      prospective randomized trial to daily use.
AB  - Routine use of vascular sealing and dissecting devices was implemented in our
      Tertiary Center of Endocrine Surgery with a high volume of thyroid operations.
      Beginning with a prospective randomized trial on 82 patients that compared
      thyroid surgery with assistance of a new, high-frequency-powered electrothermal
      device (PreciseTM, Covidien, Boulder, Colorado) to conventional thyroid surgery,
      approximately 30% of operation time was saved in the group using the device.
      Surgeons were then free to decide whether to use LigaSure (PreciseTM), an
      ultrasonic device (FocusTM, Ethicon Endo Surgery, Cincinnati, Ohio), or the
      classic tie-and-knotting procedure. This change of procedure resulted in an
      increase of surgery with devices, when compared to classic procedures from 20.2%
      to 98.4%, during a period of 5 years with 2,591 patients. The equal results of
      device-supported thyroid surgery were demonstrated when 100 consecutive patients
      with PreciseTM and FocusTM were compared, by measuring time of surgery (-36% or
      43 min) and postoperative morbidity. The authors advocate the use of vascular
      sealing and dissecting devices for thyroid operations and, especially, for
      surgical units with high operative frequency.

PMID- 19579194
TI  - Functional response imaging following neoadjuvant therapy for rectal cancer.
AB  - Neoadjuvant therapy has become the standard of care in locally advanced
      resectable rectal cancer. Increasingly, anti-angiogenic agents are incorporated
      into neoadjuvant therapy regimens. There is a need for the availability of
      biomarkers that allow one to select and monitor therapy. Functional imaging using
      dynamic MRI or PET in combination with mathematical modeling allows the
      monitoring of early vascular effects of therapy. In parallel, molecular imaging
      targeting a variety of tumor angiogenesis-associated moieties is under
      preclinical development. This chapter addresses the rationale, methods, and
      clinical data related to functional imaging of therapy response in rectal cancer.

PMID- 19579195
TI  - Experimental comparison of the stapled intestinal anastomotic techniques.
AB  - Various techniques of stapled intestinal anastomoses are performed in
      gastroenterological surgery. Little is known about which technique is optimal.
      The intestines of a domestic pig were used in this study. Stapled intestinal
      anastomoses of three types-functional end-to-end anastomosis (FETEA), stapled
      side-to-end anastomosis (STEA), and stapled end-to-end anastomosis (EEA)-were
      constructed using pig intestines. The times for constructing anastomoses, length
      of the completed anastomosed intestine, strength of anastomoses, and bursting
      locations were measured and recorded on each group. The times required to
      construct FETEAs (60 S.D. 1.4 sec) were significantly less than those required
      for STEAs (191.5 S.D. 46.4 sec) and EEAs (274.5 S.D. 54.5 sec). The mean lengths
      of the completed anastomosed intestine were significantly different for FETEAs
      (89 S.D. 8.2 mm), STEAs (135 S.D. 6.1 mm), and EEAs (156 S.D. 6.5 mm). The
      bursting pressures were not significantly different among the three groups.
      FETEAs are superior in terms of requiring less surgical time. EEAs are superior
      in terms of the length of anastomosed intestines. In conclusion, anastomotic
      techniques should be selected properly in consideration of these features.

PMID- 19579196
TI  - Double-loop puborectoplasty: novel technique for the treatment of fecal
      incontinence.
AB  - The treatment of neurogenic and traumatic fecal incontinence (FI) as may result
      from severe anal sphincteric destruction is problematic. A novel technique for
      the treatment of these cases is presented. The study comprised 44 patients, which
      included 28 with neurogenic and 16 with traumatic FI. Patients were divided into
      two equal groups. Two fascia lata slings (FLS) were applied in Group 1, while one
      sling was used in Group 2. Investigations comprised manometric and
      electromyographic studies. The procedure consisted of performing a curvilinear
      incision behind the anal orifice, and the supralevator region was entered. The
      middle of an FLS was sutured to the back of the upper part of anal canal. Each of
      the two limbs of the sling was passed forward through an incision on the pubic
      ramus and was sutured to the periosteum of the pubic ramus. This was preformed in
      Groups 1 and 2. A second FLS was added in Group 1. Its center was sutured to the
      front of the mid anal canal and its two limbs to the coccyx. Satisfactory results
      (continence scores 1 and 2) were obtained in 63.6% of Group 1 and 36.4% of Group
      2. Significant postoperative anal pressure increase occurred in scores 1 to 3 in
      Group 1 and in scores 1 to 2 in Group 2. Anal pressure increase was more
      prominent in Group 1 than in Group 2. The continent effect of the operation
      appears to be due to the increase of anal pressure, anal canal elongation, and
      recto-anal angulation. The operation is indicated in FI of the idiopathic or
      traumatic type with excessive sphincteric loss. It is simple and easy and
      performed under no cover of colostomy.

PMID- 19579197
TI  - Use of albumin polymers during breast cancer surgery improves postoperative
      seroma outcome.
AB  - The effect of an albumin polymer instillation (Bioglue(r) Cryolife, Inc.,
      Kenneaw, GA, USA) during breast cancer surgery on postoperative seroma formation
      was evaluated. Two groups of 34 consecutive patients, treated during operation
      with and without polymer, were followed postoperatively by weekly ultrasound and
      clinical evaluation. Seroma was aspirated when the volume exceeded 250 mL.
      Statistical comparison between 33 of the patients with adhesive- and 32 with non
      adhesive-treated patients showed that the former patient group clearly
      outperformed the latter in production (p<0.001) and duration (p<0.01) of seroma.
      Seroma outcome depended on body mass index (BMI) (>30 & <30, p<0.007), not on
      patient age (p<0.240) or nodes ratio (p<0.613). Repeated aspirations were made in
      37.5% non-polymer treated- and 21.21% polymer-treated patients. The findings
      demonstrated that use of albumin polymers during breast cancer surgery lowers
      postoperative seroma outcome significantly.

PMID- 19579198
TI  - Critical issues in groin hernia management.
AB  - Today's surgeon faces multiple decisions for each patient who presents with an
      inguinal hernia. The natural history of an untreated inguinal hernia is still
      unclear for a particular individual. Given the low risk of emergency and death
      from an inguinal hernia, observation alone is now becoming an acceptable approach
      for many. For those that desire or require repair, the age of the patient and
      their comorbidities will influence the choices of anesthetic and surgical
      technique. Despite our rapid advances in surgical technology, a consensus can not
      be reached locally or globally on one solution for inguinal hernia repair.
      Currently, more than six uniquely different surgical techniques are used for the
      repair of an inguinal hernia. Through the 1980s, the endpoint focused on by
      hernia surgeons was the incidence of recurrence. Though many experienced
      operators proved to have near-flawless results with a given technique, it has
      been difficult to duplicate these results by all surgeons. Over the past 10
      years, there has been a greater emphasis on the prevention of postoperative pain
      and potential long-term mesh-related issues. Laparoscopic technique and the use
      of flat, lightweight mesh are showing promise in improving inguinal hernia repair
      results.

PMID- 19579199
TI  - Less pain intensity after lichtenstein-repair by using BioGlueTM for mesh
      fixation.
AB  - A pre-trial was conducted to investigate the reliability of using the surgical
      adhesive, BioGlueTM (CryoLife(r), Inc., Kennesaw, Georgia, USA) for mesh fixation
      in Lichtenstein repair of inguinal hernia. From February to August 2008, 60
      patients with unilateral inguinal hernia underwent a Lichtenstein repair. In 30
      of the patients, BioGlueTM was used for mesh fixation and in the other 30 cases a
      conventional suture was used. The patients were sorted into two groups (BioGlueTM
      group and suture-group). No differences were noted in demographic
      characteristics. The main criteria for dropout were incarceration, relapse,
      operation, and/or scrotal hernia. Twenty-four hours postoperative, pain intensity
      was measured with a numeric analogous scale (NAS) that reached from 0 (no pain)
      to 10 (heavy pain). The pain intensity in the BioGlueTM-group was 2.4 points and
      4.3 points in the suture-group. The cut-suture time was 30 minutes in the
      BioGlueTM-group and 56 minutes in the suture-group. In the first nine months, no
      relapses, no mesh infections, nor serom-formations were reported; however, one
      superficial wound infection did occur in the BioGlueTM-group. Lichtenstein-repair
      using BioGlueTM for mesh-fixation is a safe, new method without early recurrences
      and less pain-intensity in relation to suture-supported Lichtenstein repair.

PMID- 19579200
TI  - Critical issues in groin hernia management.
AB  - Access to the posterior inguinal wall is a fundamental part of inguinal hernia
      repair. The approach to the inguinal canal may affect the course and outcome of
      the operation. The aim of this study is to compare posterior approach (PA) repair
      with the standard anterior approach (AA). The study included 91 low-risk
      unilateral primary inguinal hernia patients who randomly received AA repair or PA
      repair. Various outcome measures in both groups were compared, and the mean
      operating time was longer for the AA repair group. Intra-operative complications
      were the same in both groups. Postoperative complications were more frequent in
      the AA repair group. The at-rest mean visual analog score (VAS), 24 hours
      postoperatively, seemed to be higher in the AA repair group. AA patients were
      able to postoperatively walk sooner than PA patients. Inguinal hernia repair
      through a PA seems to be less painful, less debilitating, and more easily
      applicable than the AA. Such advantages may be the reasons to select it as a
      standard procedure of choice.

PMID- 19579201
TI  - Pre-clinical evaluation of a next-generation spray adhesion barrier for multiple
      site adhesion protection.
AB  - Intra-abdominal adhesions represent a major cause of postoperative morbidity,
      including chronic or recurrent pelvic pain and infertility in a significant
      percent of patients. The SprayShieldTM Adhesion Barrier System (Covidien,
      Waltham, MA) is a next-generation sprayable adhesion barrier to prevent
      postoperative adhesions. Initially sprayed as a liquid, SprayShieldTM solidifies
      within 2 seconds of contact with tissue through a polyethylene glycol (PEG) ester
      Trilysine reaction to form an adherent, internal tissue barrier that protects the
      underlying tissues for several days after surgery. After tissue begins to heal,
      the adhesion barrier liquefies via hydrolysis and completely absorbs within 7
      days. Safety testing has shown the product to be nongenotoxic, noncytotoxic,
      nonsensitizing, and nonirritating. SprayShieldTM has been shown to adhere well to
      tissue, with the mechanism of adherence believed to be mainly due to tissue
      surface mechanical interlocking. In studies that compared SprayShieldTM to good
      surgical technique, virgin hogs were randomized to receive SprayShieldTM or good
      surgical technique (Control). Compared to Controls, SprayShieldTM demonstrated a
      statistically significant reduction in the number of adhesions (46%, p=0.04) and
      in the area of adhesions (83%, p=0.012) to injured sites. With its ease of
      application, biocompatibility and adhesion prevention efficacy, SprayShieldTM may
      be an effective next-generation adhesion prevention product for open and
      laparoscopic abdominopelvic procedures as an adjunct to good surgical technique.

PMID- 19579202
TI  - Adhesions following surgery: pathogenesis and current experience with adhesion
      barriers.
AB  - Postoperative adhesions are a serious consequence of any type of intra-abdominal
      surgery and can result in infertility, pain, or bowel obstruction. Unfortunately,
      the paradox with adhesiolysis is that surgery performed to remove adhesions often
      results in further adhesion formation, so the problem persists and symptoms
      return and complications recur. Laparoscopic surgery with adherence to
      microsurgical techniques such as minimal tissue handling, rigorous attention to
      hemostasis, and copious irrigation was initially thought to minimize adhesion
      formation but such hopes have not been validated by clinical studies.

PMID- 19579203
TI  - Minimally invasive treatment for female stress urinary incontinence (SUI): a
      review including TVT, TOT, and mini-sling.
AB  - Treatment for female stress urinary incontinence (SUI) has progressed rapidly
      over the past ten years in the search for less invasive methods to treat this
      disease. There have been over 100 procedures described in the literature to date
      to treat female SUI; however, only two procedures have stood the test of time and
      have adequate cure rates: the retropubic colposuspension (Burch, MMK) and the
      sling. The laparoscopic approach to minimize the Burch procedure was described in
      the 1990s, but the evolution of the retropubic tension-free vaginal tape sling
      (TVT) in the late 1990s revolutionized the treatment of female SUI. More
      recently, the transobturator technique (TOT) and the single-incision mini-sling
      have been reported in attempts to further reduce the risks of sling placement.
      The current chapter reviews the history of treatment of female SUI and the
      development of these newer, less-invasive techniques. The procedures themselves
      are described, the risks of mesh complications reviewed, and the literature
      reviewed for current data on the different approaches and procedures.

PMID- 19579204
TI  - The Rotarex(r) and Aspirex(r) mechanical thrombectomy devices.
AB  - The Rotarex(r) and Aspirex(r) are newly developed over-the-wire rotational
      thrombectomy catheters. These devices combine mechanical clot fragmentation and
      active negative-pressure removal of thrombus particles to prevent distal
      embolization. Several successful in vitro studies have been followed by the
      pursuit of different applications, and the device has been used successfully in
      the treatment of acute to chronic thrombo-embolic arterial occlusions in the
      limbs, hemodialysis access grafts, bypasses, stents, pulmonary artery occlusion,
      and inferior vena cava and aortohepatic bypass occlusions. Widespread clinical
      use so far has not been achieved, and more specific indications must be
      identified to extend the experience with the Rotarex(r) and Aspirex(r) devices.

PMID- 19579205
TI  - Early results of the Birmingham mid-head resection arthroplasty.
AB  - We report the early results of 10 consecutive metal-on-metal resurfacing
      arthroplasties performed between May 2006 and July 2007 in young, active patients
      with gross femoral head defects. Failure was classified as revision for any
      reason. The mean age of our cohort at the time of surgery was 42.8 years and the
      minimal period of follow-up was 6.9 months. No patients were lost to follow-up.
      Up to the time of last review, there were no failures and all patients have
      returned to their preoperative levels of activity. This study shows promising
      early results of a bone-conserving, hydroxyapatite-coated, uncemented metal-on
      metal bearing prosthesis in young, active patients with bony defects of the
      femoral head.

PMID- 19579206
TI  - A new single-incision, soft tissue sparing approach to total hip arthroplasty: a
      case report.
AB  - Over the past decade, the development of modified instrumentation and navigation
      assistance (permitting in-situ bone excision) have stimulated advances in
      minimally invasive total hip arthroplasty techniques. These techniques have been
      developed with an objective to reduce perioperative morbidity, hospitalization
      expenses, and total rehabilitation time. Furthermore, a concomitant increase in
      the promotion of these techniques by both industry and orthopaedic surgeons
      themselves has fueled patient demand. However, the most common minimally invasive
      techniques used require two incisions and either prevent or limit the surgeon's
      ability to directly visualize the bony structures of the hip. In this chapter,
      the authors present a case study that describes a single-incision, soft-tissue
      sparing, minimally invasive technique for total hip arthroplasty.

PMID- 19579207
TI  - Effects of coronal plane conformity on tibial loading in TKA: a comparison of
      AGC(c) flat versus conforming articulations.
AB  - Conforming articulations potentially decrease polyethylene contact stresses in
      total knee arthroplasty (TKA); however, less is known about the effect of coronal
      geometry on tibial loading and clinical failure. This study examined the
      relationship between coronal plane geometry and loading patterns in the proximal
      tibia. Composite tibiae were implanted with modular, metal-backed tibial trays
      and were compressively loaded with conforming and nonconforming ultra-high
      molecular weight polyethylene (UHMWPE) tibial bearings and comparable femoral
      components. Changes in strain on the proximal tibia were quantified using a
      photoelastic strain analysis method. In balanced loading, coronally dished
      components created a strain increase in the anterior medial tibia while creating
      a significant strain decrease in the posterior tibia. Proximal tibial strains
      were decreased and centralized in conforming versus flat articulations. This
      centralization of loading may lead to a reduction in edge loading during gait.
      Lower strains were observed with coronally dished implants in key regions
      corresponding to the clinical overload of the tibia leading to aseptic loosening.

PMID- 19579208
TI  - The use of a Type-I lyophilisate collagen as an osteoinductive factor in
      pseudarthroses of the forearm.
AB  - The purpose of this study was to assess the use of a novel bone void filler
      consisting of Type I collagen and various growth factors (VEGF, TGFbeta-1,
      TGFbeta-2, IGF-1, BMP-2, BMP-3, and BMP-7) and surgical fixation to treat
      diaphyseal forearm pseudarthroses. Eleven patients underwent an osteosynthesis
      procedure for isolated pseudarthrosis fractures of the forearm (six radial and
      five ulnar diaphysis). The mean duration between the initial failed surgical
      fixation and re-operation was 38 weeks. Radiographic signs of fracture healing
      after the application of the bone void filler were noted at a mean of 5 weeks,
      and complete fracture consolidation was achieved at a mean of 6 weeks. All
      patients demonstrated improved range of motion and grip strength. Additionally,
      all patients were pain-free by 6 weeks. The combination of a novel bovine bone
      derived bone void filler and stable internal fixation led to union and rapid
      healing of forearm pseudarthroses.

PMID- 19579209
TI  - Achieving 360 degrees  fusion in high-grade spondylolisthesis using HMA screws.
AB  - Circumferential (360 degrees ) fusion yields better long-term outcome in patients
      with high-grade spondylolisthesis. This result may be achieved by combined
      anterior and posterior techniques or by an all-posterior approach. As the
      anterior approach is fraught with numerous complications, many surgeons prefer
      the all-posterior approach to achieve circumferential fusion. We have described
      in this chapter the technique of using HMA screws to achieve posterior interbody
      fusion in situ, to be combined with posterolateral fusion and pedicle screw
      instrumentation to provide the 360 degrees  fusion in high-grade
      spondylolisthesis. This technique not only provides an increased chance of
      interbody fusion because of cancellous bone but also avoids the donor site
      morbidity associated with cortical fibular strut graft.

PMID- 19579210
TI  - Three-dimensional cultures of osteogenic and chondrogenic cells: a tissue
      engineering approach to mimic bone and cartilage in vitro.
AB  - Capturing the complexity of bone and cartilage into three-dimensional in vitro
      models remains one of the most important challenges in the field of the tissue
      engineering. Indeed, the development and the optimization of novel culture
      systems may be necessary to face the next questions of bone and cartilage
      physiology. The models should faithfully mimic these tissues, resembling their
      organization, their mechanical properties and their physiological response to
      different stimuli. Here we review the recent advances in the field of the three
      dimensional cultures of both osteogenic and chondrogenic cells. In particular, we
      highlight the most important studies that, to our knowledge, have investigated
      the response of the cells to the three-dimensional environment provided by the
      diverse types of scaffold.

PMID- 19579211
TI  - Screening for glucose-triggered modifications of glutathione.
AB  - Nonenzymatic protein glycation is caused by a Schiff's base reaction between the
      aldehyde groups of reducing sugars and the primary amines of proteins. These
      structures may undergo further Amadori rearrangement and free radical-mediated
      oxidation to finally generate irreversible advanced glycation end products
      (AGEs). One of the factors known to modulate the glycation of proteins is
      glutathione, the most abundant nonprotein thiol tripeptide with the gamma
      linkage, H-Glu(Cys-Gly-OH)-OH (GSH). Screening for products formed by GSH with D
      glucose is an essential step in understanding the participation of GSH in
      glycation (the Maillard) reaction. Under the conditions used in these studies we
      observed N-(1-deoxy-D-fructos-1-yl)-pyroglutamic acid as the major glycation
      product formed in the mixtures of GSH and glucose in vitro. A RP HPLC/MS and
      tandem MS analyses of the GSH/glucose mixtures revealed that cleavage of the N
      terminal glutamic acid and the formation of pyroglutamic acid-related Amadori
      product were accompanied by generation of Cys-Gly-derived Amadori and
      thiazolidine compounds.

PMID- 19579212
TI  - Cationic oligopeptides with the repeating sequence L-lysyl-L-alanyl-L-alanine:
      conformational and thermal stability study using optical spectroscopic methods.
AB  - The infrared (IR), vibrational circular dichroism (VCD), and electronic circular
      dichroism (ECD) spectra of short cationic sequential peptides (L-Lys-L-Ala-L
      Ala)(n) (n = 1, 2, and 3) were measured over a range of temperatures (20-90
      degrees C) in aqueous solution at near-neutral pH values in order to investigate
      their solution conformations and thermally induced conformational changes. VCD
      spectra of all three oligopeptides measured in the amide I' region indicate the
      presence of extended helical polyproline II (PPII)-like conformation at room
      temperature. UV-ECD spectra confirmed this conclusion. Thus, the oligopeptides
      adopt a PPII-like conformation, independent of the length of the peptide chain.
      However, the optimized dihedral angles phi and psi are within the range -82 to 
      107 degrees and 143-154 degrees , respectively, and differ from the canonical
      PPII values. At elevated temperatures, the observed intensity and bandshape
      variations in the VCD and ECD spectra show that the PPII-like conformation of the
      Lys-Ala-Ala sequence is still preferred, being in equilibrium with an unordered
      conformer at near-neutral pH values within the range of temperatures from 20 to
      90 degrees C. This finding was obtained from analysis of the temperature
      dependent spectra using the singular value decomposition method. The study
      presents KAA-containing oligopeptides as conformationally stable models of
      biologically important cationic peptides and proteins.

PMID- 19579213
TI  - Aerobic capacity in patients with rheumatoid arthritis: a comparison of two
      submaximal test methods.
AB  - BACKGROUND: In a clinical setting it is important to evaluate aerobic capacity in
      individuals with rheumatoid arthritis (RA) and to have a choice between tests,
      owing to disability of varying severity. Two submaximal tests, a bicycle
      ergometer test and a treadmill walking test, are commonly used. Despite expected
      differences in the results, these tests have been used interchangeably. The aim
      of the current study was to compare the results of the two tests, the size of the
      difference and factors expected to influence the results. METHODS: Fifty-two
      outpatients with RA performed the two tests. Agreement and correlations between
      the results of the tests were calculated. Multivariate analysis was used to study
      the relationships between gender, weight, health assessment questionnaire, global
      health assessment and the difference between the tests. RESULTS: Sixty per cent
      of the subjects exhibited a higher estimated value of maximum oxygen uptake
      (VO(2max)) in the treadmill test. The limits of agreement for the estimated
      VO(2max) values between the two methods ranged from -13.4 to +18.4 ml x min(-1) x
      kg(-1), and the intraclass correlation coefficient (ICC(Two-way mixed)) was 0.34
      (95% confidence interval [CI] 0.07, 0.56). Body weight was independently
      associated with the difference between the two tests (regression coefficient 0.3;
      95% CI 0.14, 0.42). A higher body weight had a greater impact on the results of
      the bicycle test (R(2) = 0.28; regression coefficient -0.3; 95% CI -0.47, -0.17)
      than on the treadmill walking test (R(2) = 0.02; regression coefficient -0.06;
      95% CI -0.14, 0.03). CONCLUSIONS: It is not advisable to use the two submaximal
      methods interchangeably. Weight influenced the difference between the two tests,
      and to a higher degree in the bicycle test than the treadmill walking test.

PMID- 19579214
TI  - Selection of cell death-deficient p53 mutants in Saccharomyces cerevisiae.
AB  - The budding yeast Saccharomyces cerevisiae is a useful system for the detection
      and transcriptional evaluation of mutant p53 in cancer. In previous work we
      showed that the overexpression of wild-type p53 induces yeast cell death on
      minimal medium; however, the R248W p53 mutant was completely inactive, and we
      suggested that ROS production is a key event in p53-induced yeast cell death. In
      this study we explored the effect of other p53 mutants, such as the hot-spot
      mutant R282W and the double mutant N268S::I332V. Unexpectedly, both mutants
      behaved inversely to R248W, as they completely inhibited yeast growth on minimal
      medium and induced ROS production. This phenotype 'yeast cell death on minimal
      medium' allowed for the subsequent screening of intragenic p53-inactivating
      mutations. In all cases, the 'revertant yeast clones' display a complete p53
      inactivation through either gross deletion or nonsense mutations. More
      interestingly, missense mutations were also found: the deletion of I255 or
      substitution of R337G completely inactivated the p53 mutant R282W in the yeast
      context. Taken together, these results suggest that p53 tumour-derived mutants
      could be classified according to their ability to induce yeast cell death and not
      uniquely by their transcriptional activity on a selected target reporter gene.

PMID- 19579215
TI  - Two-stage design of clinical trials involving recurrent events.
AB  - Mixed Poisson models are often used for the design of clinical trials involving
      recurrent events since they provide measures of treatment effect based on rate
      and mean functions and accommodate between individual heterogeneity in event
      rates. Planning studies based on these models can be challenging when there is a
      little information available on the population event rates, or the extent of
      heterogeneity characterized by the variance of individual-specific random
      effects. We consider methods for adaptive two-stage clinical trial design, which
      enable investigators to revise sample size estimates using data collected during
      the first phase of the study. We describe blinded procedures in which the group
      membership and treatment received by each individual are not revealed at the
      interim analysis stage, and a 'partially blinded' procedure in which group
      membership is revealed but not the treatment received by the groups. An EM
      algorithm is proposed for the interim analyses in both cases, and the performance
      is investigated through simulation. The work is motivated by the design of a
      study involving patients with immune thrombocytopenic purpura where the aim is to
      reduce bleeding episodes and an illustrative application is given using data from
      a cardiovascular trial.

PMID- 19579216
TI  - Drug safety alert generation and overriding in a large Dutch university medical
      centre.
AB  - PURPOSE: To evaluate numbers and types of drug safety alerts generated and
      overridden in a large Dutch university medical centre. METHODS: A disguised
      observation study lasting 25 days on two internal medicine wards evaluating alert
      generation and handling of alerts. A retrospective analysis was also performed of
      all drug safety alerts overridden in the hospital using pharmacy log files over
      24 months. RESULTS: In the disguised observation study 34% of the orders
      generated a drug safety alert of which 91% were overridden. The majority of
      alerts generated (56%) concerned drug-drug interactions (DDIs) and these were
      overridden more often (98%) than overdoses (89%) or duplicate orders (80%). All
      drug safety alerts concerning admission medicines were overridden.Retrospective
      analysis of pharmacy log files for all wards revealed one override per five
      prescriptions. Of all overrides, DDIs accounted for 59%, overdoses 24% and
      duplicate orders 17%. DDI alerts of medium-level seriousness were overridden more
      often (55%) than low-level (22%) or high-level DDIs (19%). In 36% of DDI
      overrides, it would have been possible to monitor effects by measuring serum
      levels. The top 20 of overridden DDIs accounted for 76% of all DDI overrides.
      CONCLUSIONS: Drug safety alerts were generated in one third of orders and were
      frequently overridden. Duplicate order alerts more often resulted in order
      cancellation (20%) than did alerts for overdose (11%) or DDIs (2%). DDIs were
      most frequently overridden. Only a small number of DDIs caused these overrides.
      Studies on improvement of alert handling should focus on these frequently
      overridden DDIs.

PMID- 19579217
TI  - Changing from computing grid to knowledge grid in life-science grid.
AB  - Grid computing has a great potential to become a standard cyber infrastructure
      for life sciences that often require high-performance computing and large data
      handling, which exceeds the computing capacity of a single institution. Grid
      computer applies the resources of many computers in a network to a single problem
      at the same time. It is useful to scientific problems that require a great number
      of computer processing cycles or access to a large amount of data.As
      biologists,we are constantly discovering millions of genes and genome features,
      which are assembled in a library and distributed on computers around the
      world.This means that new, innovative methods must be developed that exploit the
      re-sources available for extensive calculations - for example grid computing.This
      survey reviews the latest grid technologies from the viewpoints of computing
      grid, data grid and knowledge grid. Computing grid technologies have been matured
      enough to solve high-throughput real-world life scientific problems. Data grid
      technologies are strong candidates for realizing a "resourceome" for
      bioinformatics. Knowledge grids should be designed not only from sharing explicit
      knowledge on computers but also from community formulation for sharing tacit
      knowledge among a community. By extending the concept of grid from computing grid
      to knowledge grid, it is possible to make use of a grid as not only sharable
      computing resources, but also as time and place in which people work together,
      create knowledge, and share knowledge and experiences in a community.

PMID- 19579218
TI  - A simple and robust algorithm for microarray data clustering based on gene
      population-variance ratio metric.
AB  - With the advent of the microarray technology, the field of life science has been
      greatly revolutionized, since this technique allows the simultaneous monitoring
      of the expression levels of thousands of genes in a particular organism. However,
      the statistical analysis of expression data has its own challenges, primarily
      because of the huge amount of data that is to be dealt with, and also because of
      the presence of noise, which is almost an inherent characteristic of microarray
      data. Clustering is one tool used to mine meaningful patterns from microarray
      data. In this paper, we present a novel method of clustering yeast microarray
      data, which is robust and yet simple to implement. It identifies the best
      clusters from a given dataset on the basis of the population of the clusters as
      well as the variance of the feature values of the members from the cluster
      center. It has been found to yield satisfactory results even in the presence of
      noisy data.

PMID- 19579219
TI  - Lysozyme-lysozyme self-interactions as assessed by the osmotic second virial
      coefficient: impact for physical protein stabilization.
AB  - The purpose of the presented study is to understand the physicochemical
      properties of proteins in aqueous solutions in order to identify solution
      conditions with reduced attractive protein-protein interactions, to avoid the
      formation of protein aggregates and to increase protein solubility. This is
      assessed by measuring the osmotic second virial coefficient (B(22)), a parameter
      of solution non-ideality, which is obtained using self-interaction
      chromatography. The model protein is lysozyme. The influence of various solution
      conditions on B(22) was investigated: protonation degree, ionic strength,
      pharmaceutical relevant excipients and combinations thereof. Under acidic
      solution conditions B(22) is positive, favoring protein repulsion. A similar
      trend is observed for the variation of the NaCl concentration, showing that with
      increasing the ionic strength protein attraction is more likely. B(22) decreases
      and becomes negative. Thus, solution conditions are obtained favoring attractive
      protein-protein interactions. The B(22) parameter also reflects, in general, the
      influence of the salts of the Hofmeister series with regard to their salting
      in/salting-out effect. It is also shown that B(22) correlates with protein
      solubility as well as physical protein stability.

PMID- 19579220
TI  - Molecular facets of sphingolipids: mediators of diseases.
AB  - Sphingolipids constitute a biologically active lipid class that is significantly
      important from both structural and regulatory aspects. The manipulation of
      sphingolipid metabolism is currently being studied as a novel strategy for cancer
      therapy. The basics of this therapeutic approach lie in the regulation property
      of sphingolipids on cellular processes, which are important in a cell's fate,
      such as cell proliferation, apoptosis, cell cycle arrest, senescence, and
      inflammation. Furthermore, the mutations in the enzymes catalyzing some specific
      reactions in the sphingolipid metabolism cause mortal lysosomal storage diseases
      like Fabry, Gaucher, Niemann-Pick, Farber, Krabbe, and Metachromatic
      Leukodystrophy. Therefore, the alteration of the sphingolipid metabolic pathway
      determines the choice between life and death. Understanding the sphingolipid
      metabolism and regulation is significant for the development of new therapeutic
      approaches for all sphingolipid-related diseases, as well as for cancer. An
      important feature of the sphingolipid metabolic pathway is the
      compartmentalization into endoplasmic reticulum, the Golgi apparatus, lysosome
      and plasma membrane, and this compartmentalization makes the transport of
      sphingolipids critical for proper functioning. This paper focuses on the
      structures, metabolic pathways, localization, transport mechanisms, and diseases
      of sphingolipids in Saccharomyces cerevisiae and humans, and provides the latest
      comprehensive information on sphingolipid research.

PMID- 19579222
TI  - Proteomic analysis of irregular, bullet-shaped magnetosomes in the sulphate
      reducing magnetotactic bacterium Desulfovibrio magneticus RS-1.
AB  - Recent molecular studies on magnetotactic bacteria have identified a number of
      proteins associated with bacterial magnetites (magnetosomes) and elucidated their
      importance in magnetite biomineralisation. However, these analyses were limited
      to magnetotactic bacterial strains belonging to the alpha-subclass of
      Proteobacteria. We performed a proteomic analysis of magnetosome membrane
      proteins in Desulfovibrio magneticus strain RS-1, which is phylogenetically
      classified as a member of the delta-Proteobacteria. In the analysis, the
      identified proteins were classified based on their putative functions and
      compared with the proteins from the other magnetotactic bacteria,
      Magnetospirillum magneticum AMB-1 and M. gryphiswaldense MSR-1. Three magnetosome
      specific proteins, MamA (Mms24), MamK, and MamM, were identified in strains RS-1,
      AMB-1, and MSR-1. Furthermore, genes encoding ten magnetosome membrane proteins,
      including novel proteins, were assigned to a putative magnetosome island that
      contains subsets of genes essential for magnetosome formation. The collagen-like
      protein and putative iron-binding proteins, which are considered to play key
      roles in magnetite crystal formation, were identified as specific proteins in
      strain RS-1. Furthermore, genes encoding two homologous proteins of Magnetococcus
      MC-1 were assigned to a cryptic plasmid of strain RS-1. The newly identified
      magnetosome membrane proteins might contribute to the formation of the unique
      irregular, bullet-shaped crystals in this microorganism. 

PMID- 19579223
TI  - Comparative proteomic profiles of the hepatopancreas in Fenneropenaeus chinensis
      response to hypoxic stress.
AB  - Hypoxia, as one suboptimal environmental condition, can affect the physiological
      state of shrimp during pond aquaculture. To better understand the mechanism of
      response to hypoxic stress in Chinese shrimp Fenneropenaeus chinensis, proteome
      research approach was utilized. Differentially expressed proteins of
      hepatopancreas in adult Chinese shrimp between the control and hypoxia-stressed
      groups were screened. By 2-DE analysis, 67 spots showed obvious changes after
      hypoxia. Using LC-ESI-MS/MS, 51 spots representing 33 proteins were identified
      including preamylase, arginine kinase, phosphopyruvate hydratase, citrate
      synthase, ATP synthase alpha subunit, chymotrypsin BI, chitinase, ferritin, C
      type lectin receptors, transketolase, formylglutathione hydrolase,
      formyltetrahydrofolate dehydrogenase, aldehyde dehydrogenase, glutathione
      peroxidase, cytosolic manganese superoxide dismutase, protein disulfide
      isomerase, beta-actin, oncoprotein nm23, crustacyanin-C1 and so on. These
      proteins could be functionally classified into several groups such as proteins
      related to energy production, metabolism-related proteins, immune-related
      proteins, antioxidant proteins, chaperones, cytoskeleton proteins and ungrouped
      proteins. The transcription levels of ten selected genes encode the identified
      proteins were analyzed by real-time PCR at different sampling times of hypoxia.
      This study is the first analysis of differentially expressed proteins in the
      hepatopancreas of shrimp after hypoxia and provides a new insight for further
      study in hypoxic stress response of shrimp at the protein level. 

PMID- 19579224
TI  - Quantitative correlation between mRNA secondary structure around the region
      downstream of the initiation codon and translational efficiency in Escherichia
      coli.
AB  - Translational efficiency in Escherichia coli is known to be strongly influenced
      by the secondary structure around the ribosome-binding site and the initiation
      codon in the translational-initiation region of the mRNA. Several quantitative
      studies have reported that translational efficiency is attributable to effects on
      ribosome accessibility predominantly caused by the secondary structure
      surrounding the ribosome-binding site. However, the influence of mRNA secondary
      structure around regions downstream of the initiation codon on translational
      efficiency after ribosome-binding step has not been quantitatively studied. Here,
      we quantitatively analyzed the relationship between secondary structure of mRNA
      surrounding the region downstream of the initiation codon, referred to as the
      downstream region (DR), and protein expression levels. Modified hairpin
      structures containing the initiation codon were constructed by site-directed
      mutagenesis, and their effects on expression were analyzed in vivo. The minimal
      folding free energy (DeltaG) of a local hairpin structure was found to be
      linearly correlated with the relative expression level over a range of fourfold
      change. These results demonstrate that expression level can be quantitatively
      controlled by changing the stability of the secondary structure surrounding the
      DR.

PMID- 19579225
TI  - A statistical model for the dependence between progression-free survival and
      overall survival.
AB  - Among the surrogate endpoints for overall survival (OS) in oncology trials,
      progression-free survival (PFS) is more and more taking the leading role.
      Although there have been some empirical investigations on the dependence
      structure between OS and PFS (in particular between the median OS and the median
      PFS), statistical models are almost non-existing. This paper aims at filling this
      gap by introducing an easy-to-handle model based on exponential time-to-event
      distributions that describe the dependence structure between OS and PFS. Based on
      this model, explicit formulae for individual correlations are derived together
      with a lower bound for the correlation of OS and PFS, which is given by the
      fraction of the two medians for OS and PFS. Two methods on how to estimate the
      parameter of the model from real data are discussed. One method is based on a
      maximum-likelihood estimator whereas the other method uses a plug-in approach.
      Three examples from non-small cell lung cancer are considered. In the first
      example, the parameters of the model are determined and the estimated survival
      curce is compared with the observed one. The second example explains how to
      obtain sample size estimates for OS based on assumptions on median PFS and OS.
      Finally, the third example provides a way of modelling and quantifying
      confounding effects that might explain a levelling of differences in OS although
      a difference in PFS is observed.

PMID- 19579226
TI  - Designs for dose-escalation trials with quantitative responses.
AB  - In a dose-escalation trial for a new drug, each successive dose is tested on a
      new cohort of volunteer subjects, so that if any dose produces severe adverse
      reactions then higher doses are not tested. However, if there are other
      differences between the cohorts, such as differences in environmental health
      factors, type of person or experimental procedure, then these differences may
      obscure the differences between doses. Therefore, cohorts should be fitted in the
      analysis, as either fixed or random effects. I suggest that, if this is done,
      then there are three simple principles that reduce variance (i) allocating no
      more than half the subjects in any cohort to any single dose; (ii) subject to
      safety constraints, using as many different doses as possible in each cohort;
      (iii) using one more cohort than the number of doses, without increasing the
      total number of subjects. Using these principles, I propose some new designs that
      conform to the safety rules of traditional dose-escalation trials while reducing
      the variance of the estimators of differences between the doses by a factor of
      two or more, for the same number of subjects.

PMID- 19579227
TI  - Intention to treat, per protocol, as treated and instrumental variable estimators
      given non-compliance and effect heterogeneity.
AB  - We consider the behaviour of three approaches to efficacy estimation--using so
      called 'as treated' (AT), 'per protocol' (PP) and 'instrumental variable' (IV)
      analyses--and of the Intention to Treat estimator, in a two-arm randomized
      treatment trial with a Normally distributed outcome when there is treatment
      effect heterogeneity and non-random compliance with assigned treatment. Formulae
      are derived for the bias of estimators when used either to estimate average
      treatment effect (ACE) or to estimate complier average treatment effect (CACE)
      under several models for the relationship between compliance and potential
      outcomes. These enable the expected values of AT, PP and IV estimators to be
      ranked in relation to ACE, and show that AT and PP estimators are generally
      biased for both ACE and CACE even under homogeneity. However, we show that the
      difference between any pair of (AT, PP, IV) estimates can be used to estimate the
      correlation between the latent variable determining compliance behaviour and one
      potential outcome. In the absence of measures that predict compliance, bounds for
      ACE can only be set given strong assumptions. Regarding the Intention to Treat
      estimator, while this is 'biased towards the null' if viewed as a measure of
      CACE, we show that it is not always so in relation to ACE. Finally we discuss the
      behaviour of the estimators under weak and strong null hypotheses.

PMID- 19579228
TI  - Analysis of differential proteomes in pathogenic and non-pathogenic Leptospira:
      potential pathogenic and virulence factors.
AB  - Leptospirosis is a bacterial zoonotic disease caused by spirochetes in the genus
      Leptospira. To date, factors determining the pathogenicity and virulence of
      leptospires remain unclear. We performed a gel-based proteomic analysis to
      evaluate differential leptospiral proteomes in the pathogenic L. interrogans
      (serovars Australis, Bratislava, Autumnalis, and Icterohaemorrhagiae) and the non
      pathogenic L. biflexa (serovar Patoc). Quantitative proteome analysis and MS
      protein identification revealed 42 forms of 33 unique proteins whose levels were
      significantly greater in the pathogenic serovars compared with the non-pathogenic
      serovar. Among the four pathogenic serovars, the more virulent serovar
      Icterohaemorrhagiae (which is most commonly associated with severe leptospirosis
      in patients) had significantly greater levels of 14 forms of 12 unique proteins,
      when compared with the other three pathogenic serovars. Some of these identified
      proteins may serve as the pathogenic and/or virulence factors of leptospirosis.

PMID- 19579229
TI  - Analysis of the membrane proteome of canine pancreatic rough microsomes
      identifies a novel Hsp40, termed ERj7.
AB  - The rough ER (rER) plays a central role in the biogenesis of most extracellular
      and many organellar proteins in eukaryotic cells. Cells that are specialized in
      protein secretion, such as pancreatic cells, are particularly rich in rER. In the
      process of cell homogenization, the rER is converted into ribosome-studded
      vesicles, the so-called rough microsomes. Here we report on a membrane proteomic
      analysis of canine pancreatic rough microsomes. Special emphasis was placed on
      components involved in the various aspects of protein biogenesis, such as protein
      transport, protein folding, protein modification, and protein degradation. Our
      results indicate that the Hsp70-chaperone network that is present in the
      pancreatic ER is even more complex than previously thought, and suggest that the
      pancreatic rER has a significant capacity for protein degradation.

PMID- 19579230
TI  - Comparison of oxidative capacity among leg muscles in humans using gated 31P 2-D
      chemical shift imaging.
AB  - In many small animals there are distinct differences in fiber-type composition
      among limb muscles, and these differences typically correspond to marked
      disparities in the oxidative capacities. However, whether there are similar
      differences in the oxidative capacity among leg muscles in humans is less clear.
      The purpose of this study was to compare the rate of phosphocreatine (PCr)
      recovery, a functional in vivo marker of oxidative capacity, in the lateral and
      medial gastrocnemius, soleus, and the anterior compartment of the leg (primarily
      the tibialis anterior) of humans. Subjects performed plantar flexion and
      dorsiflexion gated exercise protocols consisting of 70 sets of three rapid
      dynamic contractions (<2.86 s) at 20 s intervals (total: 23.3 min). Starting
      after the sixth set of contractions, (31)P 2-D CSI (8 x 8 matrix, 14-16 cm FOV, 3
      cm slice, TR 2.86 s) were acquired via a linear transmit/receive surface coil
      using a GE 3T Excite System. The CSI data were zero-filled (32 x 32) and a single
      FID was produced for each time point in the lateral and medial gastrocnemius,
      soleus, and anterior compartment. The time constant for PCr recovery was
      calculated from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in
      PCr due to contraction during the steady-state portion of the protocol, D the
      additional drop in PCr from rest, and Deltat is the interval between
      contractions. The tau of PCr recovery was longer (p < 0.05) in the anterior
      compartment (32 +/- 3 s) than in the lateral (23 +/- 2 s) and medial
      gastrocnemius muscles (24 +/- 3 s) and the soleus (22 +/- 3 s) muscles. These
      findings suggest that the oxidative capacity is lower in the anterior compartment
      than in the triceps surae muscles and is consistent with the notion that fiber
      type phenotypes vary among the leg muscles of humans.

PMID- 19579233
TI  - Magnetism in nanoparticles: beyond the effect of particle size.
AB  - A set of investigations on selected samples of nanosized cobalt ferrite are
      reviewed, aimed at studying the various factors affecting the magnetic properties
      of nanoparticles. Specifically, the effects of inter-particle interactions, of
      structural and magnetic order, both in the core and on the surface of the
      particle, have been examined. All factors render the control of the magnetic
      properties of nanosystems quite difficult, but, at the same time, they also offer
      the opportunity of tuning them properly, so that materials for specific
      applications may be created.

PMID- 19579231
TI  - Phosphoproteomic analysis of the human pathogen Trypanosoma cruzi at the
      epimastigote stage.
AB  - Trypanosoma cruzi is the etiologic agent of Chagas disease, which affects
      millions of people in Latin America and has become a public health concern in the
      United States and areas of Europe. The possibility that kinase inhibitors
      represent novel anti-parasitic agents is currently being explored. However,
      fundamental understanding of the cell-signaling networks requires the detailed
      analysis of the involved phosphorylated proteins. Here, we have performed a
      comprehensive MS-based phosphorylation mapping of phosphoproteins from T. cruzi
      epimastigote forms. Our LC-MS/MS, dual-stage fragmentation, and multistage
      activation analysis has identified 237 phosphopeptides from 119 distinct
      proteins. Furthermore, 220 phosphorylation sites were unambiguously mapped: 148
      on serine, 57 on threonine, and 8 on tyrosine. In addition, immunoprecipitation
      and Western blotting analysis confirmed the presence of at least seven tyrosine
      phosphorylated proteins in T. cruzi. The identified phosphoproteins were
      subjected to Gene Ontology, InterPro, and BLAST analysis, and categorized based
      on their role in cell structure, motility, transportation, metabolism,
      pathogenesis, DNA/RNA/protein turnover, and signaling. Taken together, our
      phosphoproteomic data provide new insights into the molecular mechanisms governed
      by protein kinases and phosphatases in T. cruzi. We discuss the potential roles
      of the identified phosphoproteins in parasite physiology and drug development.

PMID- 19579234
TI  - New mechanistic aspects of the Fenton reaction.
AB  - The kinetics of the Fenton reaction was studied in detail. A second reaction step
      in the presence of excess H2O2 is attributed to formation of the complex Fe(III)(
      O2H)(aq). Therefore, the reaction of Fe(H2O)(6)(2+) with Fe(III)(-O2H)(aq) in the
      presence of Fe(II) to form Fe(III)(aq) (k=(7.7+/-1.5) x 10(5) M(-1) s(-1)) may
      contribute to the overall Fenton reaction, and could account for some of the
      debate in the literature concerning its detailed mechanism. If this is correct
      for LFe(III)(-O2H)(aq) also, then it might be of significant biological
      importance. The activation parameters DeltaH(not equal), DeltaS(not equal), and
      DeltaV(not equal) for the Fenton reaction were measured under various
      experimental conditions, and are used in the mechanistic interpretation.

PMID- 19579232
TI  - O-Glycosylated 24 kDa human growth hormone has a mucin-like biantennary
      disialylated tetrasaccharide attached at Thr-60.
AB  - MS was used to characterize the 24 kDa human growth hormone (hGH) glycoprotein
      isoform and determine the locus of O-linked oligosaccharide attachment, the
      oligosaccharide branching topology, and the monosaccharide sequence. MALDI-TOF/MS
      and ESI-MS/MS analyses of glycosylated 24 kDa hGH tryptic peptides showed that
      this hGH isoform is a product of the hGH normal gene. Analysis of the
      glycoprotein hydrolysate by high-performance anion-exchange chromatography with
      pulsed amperometric detection and HPLC with fluorescent detection for N-acetyl
      neuraminic acid (NeuAc) yielded the oligosaccharide composition (NeuAc(2), N
      acetyl galactosamine(1), Gal(1)). After beta-elimination to release the
      oligosaccharide from glycosylated 24 kDa hGH, collision-induced dissociation of
      tryptic glycopeptide T6 indicated that there had been an O-linked oligosaccharide
      attached to Thr-60. The sequence and branching structure of the oligosaccharide
      were determined by ESI-MS/MS analysis of tryptic glycopeptide T6. The mucin-like
      O-oligosaccharide sequence linked to Thr-60 begins with N-acetyl galactosamine
      and branches in a bifurcated topology with one appendage consisting of galactose
      followed by NeuAc and the other consisting of a single NeuAc. The oligosaccharide
      moiety lies in the high-affinity binding site 1 structural epitope of hGH that
      interfaces with both the growth hormone and the prolactin receptors and is
      predicted to sterically affect receptor interactions and alter the biological
      actions of hGH.

PMID- 19579235
TI  - Position-dependent effects of fluorinated amino acids on the hydrophobic core
      formation of a heterodimeric coiled coil.
AB  - Systematic model investigations of the molecular interactions of fluorinated
      amino acids within native protein environments substantially improve our
      understanding of the unique properties of these building blocks. A rationally
      designed heterodimeric coiled coil peptide (VPE/VPK) and nine variants containing
      amino acids with variable fluorine content in either position a16 or d19 within
      the hydrophobic core were synthesized and used to evaluate the impact of
      fluorinated amino acid substitutions within different hydrophobic protein
      microenvironments. The structural and thermodynamic stability of the dimers were
      examined by applying both experimental (CD spectroscopy, FRET, and analytical
      ultracentrifugation) and theoretical (MD simulations and MM-PBSA free energy
      calculations) methods. The coiled coil environment imposes position-dependent
      conformations onto the fluorinated side chains and thus affects their packing and
      relative orientation towards their native interaction partners. We find evidence
      that such packing effects exert a significant influence on the contribution of
      fluorine-induced polarity to coiled coil folding.

PMID- 19579237
TI  - Temperature-dependent guest-driven single-crystal-to-single-crystal ligand
      exchange in a two-fold interpenetrated Cd(II) grid network.
AB  - A doubly interpenetrated square-grid coordination polymer
      {[Cd(ImBNN)(2)(CF(3)SO(3))(2)])guest}(n) (1) (guest = C(7)H(8) and ImBNN = 2,5
      bis[4'-(imidazol-1-yl)phenyl]-3,4-diaza-2,4-hexadiene) that contains cavities
      able to accommodate toluene guest molecules has been assembled by the reaction of
      the Schiff base ligand ImBNN and Cd(CF(3)SO(3))(2). The framework 1 shows
      dynamism in either temperature-dependent expansion and shrinkage or cooperatively
      temperature-dependent guest-driven ligand exchange at the metal center. Studies
      of guest removal/uptake by heating in a vacuum, cooling in air, and then heating
      in toluene at reflux have revealed a series of single-crystal-to-single-crystal
      structural transformations: complex 1 lost toluene guests and captured water
      molecules to give guest-free 1 b via a proposed metastable phase 1 a, and 1 b
      could readsorb toluene guests to give 1', which represents a restored 1. These
      structural changes establish an indirect recoverable process that involves ligand
      exchange in the coordination sphere and guest exchange in the cavity accompanied
      by the cleavage/formation of Cd-O bonds and CF(3)SO(3)(-) anion-shifting. In
      contrast, direct heating of 1 in the absence of a vacuum resulted in thermostable
      1 c, confirmed by X-ray powder diffraction as a new phase that could not be
      converted back into 1 and that had lost the ability of readsorbing toluene
      guests.

PMID- 19579236
TI  - A kinetic and structural investigation of DNA-based asymmetric catalysis using
      first-generation ligands.
AB  - The recently developed concept of DNA-based asymmetric catalysis involves the
      transfer of chirality from the DNA double helix in reactions using a
      noncovalently bound catalyst. To date, two generations of DNA-based catalysts
      have been reported that differ in the design of the ligand for the metal. Herein
      we present a study of the first generation of DNA-based catalysts, which contain
      ligands comprising a metal-binding domain linked through a spacer to a 9
      aminoacridine moiety. Particular emphasis has been placed on determining the
      effect of DNA on the structure of the Cu(II) complex and the catalyzed Diels
      Alder reaction. The most important findings are that the role of DNA is limited
      to being a chiral scaffold; no rate acceleration was observed in the presence of
      DNA. Furthermore, the optimal DNA sequence for obtaining high
      enantioselectivities proved to contain alternating GC nucleotides. Finally, DNA
      has been shown to interact with the Cu(II) complex to give a chiral structure.
      Comparison with the second generation of DNA-based catalysts, which bear
      bipyridine-type ligands, revealed marked differences, which are believed to be
      related to the DNA microenvironment in which the catalyst resides and where the
      reaction takes place.

PMID- 19579238
TI  - Neutral pentacoordinate silicon(IV) complexes with silicon-chalcogen (S, Se, Te)
      bonds.
AB  - The neutral pentacoordinate silicon(IV) complexes 1 (SiS2ONC skeleton), 2
      (SiSeSONC), 3 (SiTeSONC), 6/9 (SiSe2O2C), 7 (SiSe2S2C), and 8/10 (SiSe4C) were
      synthesized and structurally characterized by using single-crystal X-ray
      diffraction and multinuclear solid-state and solution-state (except for 6-9) NMR
      spectroscopy. With the synthesis of compounds 1-3 and 6-10, it has been
      demonstrated that pentacoordinate silicon compounds with soft chalcogen ligand
      atoms (S, Se, Te) can be stable in the solid state and in solution.

PMID- 19579239
TI  - Helical chiral pyridine N-oxides: a new family of asymmetric catalysts.
AB  - Optically active chiral alkyl chlorides are valuable compounds because of their
      bioactivity and versatile synthetic utility. Accordingly, the ring opening of
      epoxides with a chloride nucleophile stands as an important goal in asymmetric
      catalysis. We describe herein recent advances in the design and development of
      chiral pyridine N-oxide catalysts for the enantioselective synthesis of
      chlorohydrins.

PMID- 19579240
TI  - Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse
      polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase
      inhibitory properties.
AB  - The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars
      generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-alpha
      substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is
      reported. L-fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate
      aldolase (RhuA) from E. coli were used as biocatalysts to generate
      configurational diversity on the iminosugars. Alkyl linear substitutions at C
      alpha were well tolerated by FucA catalyst (i.e., 40-70 % conversions to aldol
      adduct), whereas no product was observed with C-alpha-alkyl branched
      substitutions, except for dimethyl and benzyl substitutions (20 %). RhuA was the
      most versatile biocatalyst: C-alpha-alkyl linear groups gave the highest
      conversions to aldol adducts (60-99 %), while the C-alpha-alkyl branched ones
      gave moderate to good conversions (50-80 %), with the exception of dimethyl and
      benzyl substituents (20 %). FucA was the most stereoselective biocatalyst (90-100
      % anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2
      aminoaldehydes (90-100 % syn (i.e., 3R,4S) adduct), whereas those with R
      configuration gave mixtures of anti/syn adducts. For iPr and iBu substituents,
      RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high
      stereoselectivity. Molecular models of aldol products with iPr and iBu
      substituents and as complexes with the RhuA active site suggest that the anti
      adducts could be kinetically preferred, while the syn adducts would be the
      equilibrium products. The polyhydroxylated pyrrolidines generated were tested as
      inhibitors against seven glycosidases. Among them, good inhibitors of alpha-L
      fucosidase (IC50=1-20 microM), moderate of alpha-L-rhamnosidase (IC50=7-150
      microM), and weak of alpha-D-mannosidase (IC50=80-400 microM) were identified.
      The apparent inhibition constant values (Ki) were calculated for the most
      relevant inhibitors and computational docking studies were performed to
      understand both their binding capacity and the mode of interaction with the
      glycosidases.

PMID- 19579241
TI  - A click-click approach for the preparation of functionalized [5:1]-hexaadducts of
      C60.

PMID- 19579242
TI  - Is the backbone conformation of C(alpha)-methyl proline restricted to a single
      region?
AB  - C(alpha)-methyl-L-proline, or L-(alphaMe)Pro, is probably the most
      conformationally constrained alpha-amino acid. In particular, its omega and phi
      torsion angles are restricted to about 180 and -60 degrees, respectively, and
      only three ranges of values are theoretically available for psi in mono- or
      longer peptides, namely, about -30 degrees (cis', 3(10)/alpha-helical structure),
      60 degrees (inverse gamma turn), or 140 degrees (trans', poly(L-Pro)(n) II
      structure). In this work, we examined the tendency of a number of N(alpha)-acyl
      dipeptide N'-alkylamides of the type RCO-(alphaMe)Pro-Xxx-NHR' or RCO-Xxx
      (alphaMe)Pro-NHR', in which Xxx is L (or D)-Ala, Aib (alpha-aminoisoburyric
      acid), or L (or D)-(alphaMe)Pro, long enough to fold into intramolecularly
      hydrogen-bonded gamma or beta turns. The results are compared with those obtained
      for the corresponding dipeptides based on Pro, a well-known turn-forming residue.
      For the crystal-state 3D-structural analysis we used X-ray diffraction, whereas
      our solution conformational analysis was heavily based on the FTIR absorption and
      (1)H and (13)C NMR spectroscopy techniques. We conclude that (alphaMe)Pro is able
      to explore both trans' and cis' psi areas of the conformational space, but in
      (alphaMe)Pro the latter is overwhelmingly more populated, in marked contrast to
      the Pro preference. This finding is a clear indication that in (alphaMe)Pro the
      major 3D-structural determinant is the C(alpha)-methyl group. The circular
      dichroism (CD) signature of a peptide type III' beta-turn conformation is also
      proposed.

PMID- 19579243
TI  - Highly water-dispersible biocompatible magnetite particles with low cytotoxicity
      stabilized by citrate groups.

PMID- 19579244
TI  - Expedient synthesis of N-fused indoles: a C-F activation and C-H insertion
      approach.

PMID- 19579245
TI  - Switching the chirality of the metal environment alters the coordination mode in
      designed peptides.

PMID- 19579246
TI  - Total synthesis of (+)-haplophytine.

PMID- 19579247
TI  - Discovery of green fluorescent protein (GFP) (Nobel Lecture).

PMID- 19579248
TI  - Characterisation of a recombinant NADP-dependent glycerol dehydrogenase from
      Gluconobacter oxydans and its application in the production of L-glyceraldehyde.
AB  - The acetic acid bacterium Gluconobacter oxydans has a high potential for
      oxidoreductases with a variety of different catalytic abilities. One putative
      oxidoreductase gene codes for an enzyme with a high similarity to the NADP+
      dependent glycerol dehydrogenase (GlyDH) from Hypocrea jecorina. Due to this
      homology, the GlyDH (Gox1615) has been cloned, over-expressed in Escherichia
      coli, purified and characterised. Gox1615 shows an apparent native molecular mass
      of 39 kDa, which corresponds well to the mass of 37.213 kDa calculated from the
      primary structure. From HPLC measurements, a monomeric structure can be deduced.
      Kinetic parameters and the dependence of the activity on temperature and pH were
      determined. The enzyme shows a broad substrate spectrum in the reduction of
      different aliphatic, branched and aromatic aldehydes. Additionally, the enzyme
      has been shown to oxidize a variety of different alcohols. The highest activities
      were observed for the conversion of D-glyceraldehyde in the reductive and L
      arabitol in the oxidative direction. Since high enantioselectivities were
      observed for the reduction of glyceraldehyde, the kinetic resolution of
      glyceraldehyde was investigated and found to yield enantiopure L-glyceraldehyde
      on preparative scale.

PMID- 19579249
TI  - A vibrational Raman optical activity study of 1,1'-binaphthyl derivatives.
AB  - The Raman polarized and vibrational Raman optical activity (VROA) backward
      spectra are simulated for a series of 2,2'-substituted 1,1'-binaphthyl compounds
      presenting a variety of torsion angles between the two naphthalene rings. The
      substitution prevents free rotation along this torsion angle and the chirality of
      these compounds is thus called atropisomerism. However, the rotation is not
      completely frozen so that two different conformations, namely cisoid and
      transoid, are found and their Raman and VROA signatures are studied. As expected,
      the Raman spectra are not very sensitive whereas the VROA spectra present more
      complex patterns, which evolve as a function of the torsion angle between the two
      naphthalene groups. In particular, our analysis shows that some modes can be used
      as a probe for the determination of the torsion angle of these molecules in
      solution. The contributions of both invariants to the VROA backward intensity are
      also assessed.

PMID- 19579250
TI  - Nanowire-based polypyrrole hierarchical structures synthesized by a two-step
      electrochemical method.
AB  - A simple two-step electrochemical method is proposed for the synthesis of
      nanowire-based polypyrrole hierarchical structures. In the first step,
      microstructured polypyrrole films are prepared by electropolymerization. Then,
      polypyrrole nanowires are electrodeposited on the surface of the as-synthesized
      microstructured polypyrrole films. As a result, hierarchical structures of
      polypyrrole nanowires on polypyrrole microstructures are obtained. The surface
      wettabilities of the resulting nanowire-based polypyrrole hierarchical structures
      are examined. It is expected that this two-step method can be developed into a
      versatile route to produce nanowire-based polypyrrole hierarchical structures
      with different morphologies and surface properties.

PMID- 19579251
TI  - Electrocatalytic recycling of CO2 and small organic molecules.
AB  - As global warming directly affects the ecosystems and humankind in the 21st
      century, attention and efforts are continuously being made to reduce the emission
      of greenhouse gases, especially carbon dioxide (CO2). In addition, there have
      been numerous efforts to electrochemically convert CO2 gas to small organic
      molecules (SOMs) and vice versa. Herein, we highlight recent advances made in the
      electrocatalytic recycling of CO2 and SOMs including (i) the overall trend of
      research activities made in this area, (ii) the relations between reduction
      conditions and products in the aqueous phase, (iii) the challenges in the use of
      gas diffusion electrodes for the continuous gas phase CO2 reduction, as well as
      (iv) the development of state of the art hybrid techniques for industrial
      applications. Perspectives geared to fully exploit the potential of zero-gap
      cells for CO2 reduction in the gaseous phase and the high applicability on a
      large scale are also presented. We envision that the hybrid system for CO2
      reduction supported by sustainable solar, wind, and geothermal energies and waste
      heat will provide a long term reduction of greenhouse gas emissions and will
      allow for continued use of the abundant fossil fuels by industries and/or power
      plants but with zero emissions.

PMID- 19579252
TI  - Calixarene dimers as host molecules for biologically important di- and
      oligophosphates.
AB  - A dimeric calixarene, with an aliphatic C(6)-bridge and six anilinium head groups
      at its upper rim, preferably complexes diphosphates and oligonucleotides with
      more than 10 bonds between both anionic moieties. Free binding energies correlate
      with the length of the aliphatic bridge in a roughly linear fashion. The binding
      event, which is monitored by fluorescence titrations and competition experiments,
      relies on Coulomb interactions, as opposed to a nonpolar variant with tert-butyl
      instead of ammonium groups; here, hydrophobic forces prevail, rendering the
      calixarene dimer selective for less polar cofactors such as FAD. The best guest
      for the hexaanilinium dimer is found in ssDNA, which carries multiple copies of
      the optimal trinucleotide for maximum attraction towards the extended cationic
      host. The recognition event is also observed in the environment of a lipid
      monolayer, and provides a means to quantify dimer diphosphate interactions by
      measuring p/A shifts.

PMID- 19579253
TI  - Preparation of C(3)-symmetric homochiral syn-trisnorbornabenzenes through
      regioselective cyclotrimerization of enantiopure iodonorbornenes.
AB  - C(3)-symmetric homochiral (-)-syn-trisoxonorbornabenzene 1 possessing a rigid cup
      shaped structure was synthesized through a novel regioselective
      cyclotrimerization of enantiopure iodonorbornenes catalyzed by palladium
      nanoclusters. The yield of the cyclotrimerization was dependent on the stability
      of the palladium clusters, which was ascertained from the appearance and TEM
      images of the reaction mixtures. The efficient preparation of (-)-syn-1 was
      established in short steps, including the newly developed cyclotrimerization
      reaction. The thus-prepared homochiral (-)-syn-1 can serve as a key intermediate
      for the synthesis of C(3)-symmetric homochiral cup-shaped molecules with a
      helical arrangement of substituents. Introduction of several types of
      substituents was well demonstrated through palladium-catalyzed coupling reactions
      with the corresponding phosphate and triflate of (-)-syn-1.

PMID- 19579254
TI  - Osmium-mediated oxidative cyclizations: a study into the range of initiators that
      facilitate cyclization.
AB  - A general route to prepare substituted, saturated five-membered heterocycles has
      been developed. The application of a wide range of starting materials to the
      osmium-catalyzed oxidative cyclization reaction is described. Diols, hydroxy
      amides, hydroxy-sulfonamides, and carbamates all cyclize in moderate to excellent
      yields to give cis-tetrahydrofurans and pyrrolidines, depending upon the position
      of the heteroatoms in the starting materials. These cyclizations all proceed with
      near total selectivity for the cis-heterocycles, and with stereospecific
      introduction of a hydroxy group adjacent to the ring. Moreover, routes to
      enantiopure starting materials are described, which give enantiopure products
      upon cyclization. Catalyst loadings of as low as one mol percent have been
      successfully employed for this transformation.

PMID- 19579255
TI  - Ester hydrolysis by a cyclodextrin dimer catalyst with a tridentate N,N',N''-zinc
      linking group.
AB  - A new beta-cyclodextrin dimer, 2,6-dimethylpyridine-bridged-bis(6-monoammonio
      beta-cyclodextrin) (pyridyl BisCD, L), is synthesized. Its zinc complex (ZnL) is
      prepared, characterized, and applied as a catalyst for diester hydrolysis. The
      formation constant (log K(ML)=7.31+/-0.04) of the complex and deprotonation
      constant (pK(a1)=8.14+/-0.03, pK(a2)=9.24+/-0.01) of the coordinated water
      molecule were determined by a potentiometric pH titration at (25+/-0.1) degrees
      C, indicating a tridentate N,N',N''-zinc coordination. Hydrolysis kinetics of
      carboxylic acid esters were determined with bis(4-nitrophenyl)carbonate (BNPC)
      and 4-nitrophenyl acetate (NA) as the substrates. The resulting hydrolysis rate
      constants show that ZnL has a very high rate of catalysis for BNPC hydrolysis,
      yielding an 8.98x10(3)-fold rate enhancement over uncatalyzed hydrolysis at pH
      7.00, compared to only a 71.76-fold rate enhancement for NA hydrolysis.
      Hydrolysis kinetics of phosphate esters catalyzed by ZnL are also investigated
      using bis(4-nitrophenyl)phosphate (BNPP) and disodium 4-nitrophenyl phosphate
      (NPP) as the substrates. The initial first-order rate constant of catalytic
      hydrolysis for BNPP was 1.29x10(-7) s(-1) at pH 8.5, 35 degrees C and 0.1 mM
      catalyst concentration, about 1600-fold acceleration over uncatalyzed hydrolysis.
      The pH dependence of the BNPP cleavage in aqueous buffer was shown as a sigmoidal
      curve with an inflection point around pH 8.25, which is nearly identical to the
      pK(a) value of the catalyst from the potentiometric titration. The k(BNPP) of
      BNPP hydrolysis promoted by ZnL is found to be 1.68x10(-3) M(-1) s(-1), higher
      than that of NPP, and comparatively higher than those promoted by its other
      tridentate N,N',N''-zinc analogues.

PMID- 19579256
TI  - Improvement of targeted gene delivery to human cancer cells by a novel
      trifunctional crosslinker.
AB  - A facile method for the construction of an immunoconjugate which displays
      targeting ligands, such as antibody fragments, with a high density is reported.
      For this purpose, we synthesized a novel trifunctional crosslinking reagent. By
      the use of this reagent, ligands targeting the specific cell can be displayed on
      the surface of the drug carrier with a high density. In this study, we display
      HER2 (human epidermal growth-factor receptor-2) binding ligands on branched
      polyethylenimine (PEI), which can form polyplexes with plasmid DNA. Kinetic
      analysis of the binding to the extracellular domain of HER2 show the PEI
      displaying a high density of ligands binds to the target more strongly compared
      to the PEI displaying ligands at a low density. The increased density of HER2
      ligands displayed on the gene carrier contributes to the improved transfection
      efficiency. This approach can be applied to other drug delivery systems,
      including liposome, micelle, and so on.

PMID- 19579257
TI  - The efficient one-pot reaction of up to eight components by the union of
      multicomponent reactions.

PMID- 19579258
TI  - Classification of prostatic diseases by means of multivariate analysis on in vivo
      proton MRSI and DCE-MRI data.
AB  - Multivariate analysis has been applied on proton magnetic resonance spectroscopic
      imaging ((1)H-MRSI) and dynamic contrast enhanced MRI (DCE-MRI) data of patients
      with different prostatic diseases such as chronic inflammation, fibrosis and
      adenocarcinoma. Multivariate analysis offers a global view of the entire range of
      information coming from both the imaging and spectroscopic side of NMR
      technology, leading to an integrated picture of the system relying upon the
      entire metabolic and dynamic profile of the studied samples. In this study, we
      show how this approach, applied to (1)H-MRSI/DCE-MRI results, allows us to
      differentiate among the various prostatic diseases in a non-invasive way with a
      100% accuracy. These findings suggest that multivariate analysis of (1)H-MRSI/DCE
      MRI can significantly improve the diagnostic accuracy for these pathological
      entities. From a more theoretical point of view, the complementation of a single
      biomarker approach with an integrated picture of the entire metabolic and dynamic
      profile allows for a more realistic appreciation of pathological entities.

PMID- 19579259
TI  - Forum highlights new government focus on cancer research.

PMID- 19579260
TI  - The effects of harassment severity and organizational behavior on damage awards
      in a hostile work environment sexual harassment case.
AB  - Community members reporting for jury duty (N = 128) read a sexual harassment
      trial summary in which harassment severity and the organization's sexual
      harassment policy and response were manipulated. Jurors who read the severe
      harassment scenario were more likely to agree that the plaintiff had suffered and
      should be compensated for her suffering and that the organization should be
      punished than were jurors who read the mild harassment scenario. When the
      organization had and enforced a sexual harassment policy, jurors believed that
      the plaintiff had suffered little and the organization should not be punished
      compared with conditions in which the organization did not have an enforced
      sexual harassment policy. Harassment severity influenced jurors' compensatory
      awards, and organizational behavior influenced jurors' punitive awards. These
      results have implications for plaintiffs, who must decide whether to claim
      specific or garden-variety damages; organizations, which could create or modify
      sexual harassment policy to limit damages; and trial lawyers, who could tailor
      arguments to maximize or minimize awards.

PMID- 19579261
TI  - Support/services among family caregivers of persons with dementia--perceived
      importance and services received.
AB  - OBJECTIVE: The aim of this study was to examine what family caregivers of persons
      with dementia perceive as important types of support/services in relation to
      experienced negative impact (NI) due to the caregiver situation, and to
      investigate if caregivers receive the support/services perceived as important.
      METHOD: The study was based on the Swedish part of the EUROFAMCARE project and
      included 110 caregivers of persons with dementia. Data were collected primarily
      through structured telephone interviews. The caregivers were divided into two
      groups, a higher NI group and a lower NI group, based on the NI scale from the
      COPE index. RESULTS: Getting information and having someone to talk to were
      perceived as very important types of support/services by the highest proportion
      of caregivers in both groups. Data indicated only one significant difference; a
      higher proportion of caregivers in the higher NI group reported being able to
      participate in activities outside of caring as very important. There was also an
      indication that a higher proportion of caregivers in the lower NI group perceived
      information about the disease as very important. Support/services perceived as
      important by the caregivers were received both to a high and a low degree.
      CONCLUSION: The results from this study suggest that there is almost no
      difference between groups of caregivers experiencing higher and lower NI
      regarding their perception of what are important types of support/services. The
      caregivers rated different types of support/services within the areas of
      information, relief and counselling as very important.

PMID- 19579263
TI  - Validated quantitation method for a peptide in rat serum using liquid
      chromatography/high-field asymmetric waveform ion mobility spectrometry.
AB  - The analysis of peptides presents serious challenges for bioanalytical scientists
      including low total ion current and non-selective fragmentation during tandem
      mass spectrometry (MS/MS). During method validation of a peptide in rat serum
      matrix some interferences could not be easily removed and thus prevented accurate
      and precise measurement. These problems associated with peptide quantitation were
      resolved by using FAIMS (high-Field Asymmetric waveform Ion Mobility
      Spectrometry). This selectivity-enhancing technique filters out matrix
      interferences, and the resulting pseudo-selected reaction monitoring (pseudo-SRM)
      chromatograms were nearly free from interferences. Control blank matrix samples
      contained an acceptable level of interference (only 7% signal as compared to the
      lower level of quantitation). Chromatographic peaks were easily, accurately and
      precisely integrated resulting in a validated liquid chromatography (LC)/FAIMS
      MS/MS method for the analysis of a peptide drug in rat serum according to United
      States Food and Drug Administration (US FDA) bioanalytical guidelines. These
      results confirm that new selectivity-enhancing technologies aid the
      pharmaceutical industry in reliably producing acceptable pharmacokinetic data.

PMID- 19579262
TI  - A cataluminescence gas sensor for ammonium sulfide based on Fe(3)O(4)-carbon
      nanotubes composite.
AB  - In the present work, Fe(3)O(4)-carbon nanotubes (CNTs) composite was explored as
      a sensing material candidate for ammonium sulfide. Intense chemiluminescence
      emission can be observed during the catalytic oxidation of ammonium sulfide on
      the surface of Fe(3)O(4)-CNTs composite. Based on this phenomenon, a selective
      and sensitive gas sensor for the determination of ammonium sulfide was
      demonstrated. Under the optimized conditions, the linear range of
      cataluminescence intensity vs concentration of ammonium sulfide gas was 1.4-115
      microg mL(-1) (R = 0.998) with a limit of detection (S/N = 3) of 0.05 microg mL(
      1). The relative standard deviation (n = 5) for 14.3 microg mL(-1) ammonium
      sulfide was 1.9%. There was no response to common foreign substances, such as
      sulfur dioxide, toluene, aether, ethanol, acetone, hydrogen sulfide, carbon
      bisulfide, benzene and ammonia. The proposed sensor was successfully applied for
      the determination of ammonium sulfide in artificial air samples.

PMID- 19579264
TI  - Volatile composition of Brassica oleracea L. var. costata DC leaves using solid
      phase microextraction and gas chromatography/ion trap mass spectrometry.
AB  - Volatile and semi-volatile components of internal and external leaves of Brassica
      oleracea L. var. costata DC, grown under different fertilization regimens, were
      determined by headspace solid-phase microextraction (HS-SPME) combined with gas
      chromatography/ion trap mass spectrometry (GC/ITMS). Forty-one volatiles and non
      volatile components were formally identified and thirty others were tentatively
      identified. Qualitative and quantitative differences were noticed between
      internal and external leaves. In general, internal leaves exhibited more
      aldehydes and sulfur volatile compounds than external ones, and less ketone,
      terpenes and norisoprenoid compounds. The fertilization regimens influenced
      considerably the volatile profile. Fertilizations with higher levels of sulfur
      produced Brassica leaves with more sulfur volatiles. In opposition, N and S
      fertilization led to leaves with lower levels of norisoprenoids and terpenes.

PMID- 19579265
TI  - Structural studies on aryl-substituted enaminoketones and their thio analogues.
      Part I. Analysis of high-resolution (1)H, (13)C NMR and (13)C CP MAS spectra
      combined with GIAO-DFT calculations.
AB  - A series of aryl-substituted enaminoketones and their thio analogues in CDCl(3)
      solution and in the solid state were studied by the use of high-resolution (1)H
      and (13)C as well as (13)C cross polarization magic angle spinning (CP MAS) NMR
      spectra in combination with gauge including atomic orbitals-density functional
      theory (GIAO-DFT) calculations performed at the B3PW91/6-311 + + G(d,p) level of
      theory using the B3PW91/6-311 + + G(d,p)-optimized geometries. The analysis of
      the (13)C NMR spectra in solution was done by using the Incredible Natural
      Abundance DoublE QUAntum Transfer Experiment (INADEQUATE) technique, whereas
      trends observed in the (13)C shielding constants, calculated for the compounds
      studied, were a great help in assigning most of the signals in the (13)C CP MAS
      NMR spectra. It was established on the basis of the experimental and theoretical
      NMR data that both groups of compounds exist in the form of Z-s-Z-s-E isomers in
      CDCl(3) solution as well as in the solid state, with the NH hydrogen atom
      involved in intramolecular hydrogen bonding. This conclusion is in agreement with
      the fact that some of the compounds studied reveal liquid-crystalline properties.
      Three-bond H, H and C, H coupling constants measured in solution played a crucial
      role in the structure elucidation.

PMID- 19579266
TI  - Efficient activation of p53 pathway in A549 cells exposed to L2, a novel compound
      targeting p53-MDM2 interaction.
AB  - The tumor suppressor p53 plays a key role in the regulation of cell cycle,
      apoptosis, DNA repair, and senescence. It acts as a transcriptional factor, and
      is able to activate various genes to exert specific functions. MDM2, the main
      regulator of p53, inhibits the function of p53 through direct interaction. On the
      basis of this finding, inhibiting the MDM2-p53 interaction can be a potentially
      important target for cancer therapy. We showed here that L2, an analog of small
      molecule MDM2 antagonist nutlins, stabilized p53 and selectively activated the
      p53 pathway in p53 wild-type A549 cells, resulting in a pronounced
      antiproliferation effect through inducing cell cycle arrest and apoptosis.
      Meanwhile, we confirmed by immunoprecipitation analysis that L2 could also
      inhibit MDM2-p53 interaction, similar to nutlin-1. Real-time PCR results revealed
      that L2 had no effect on the p53 gene transcriptional level, but it could induce
      the upregulation of p21 at the transcriptional level, which was the downstream of
      p53. Therefore, we concluded that the accumulation of p53 caused by L2 was mainly
      because of the decrease of the protein degradation rather than the elevation of
      p53 gene expression. Furthermore, no phosphor-p53 formed after L2 treatments,
      indicating that a genetoxic mechanism was unlikely to contribute to the
      activation of p53 by L2. In conclusion, the data acquired from A549 cells
      indicated that L2 exhibited high antiproliferation activity by disrupting MDM2
      p53 interaction, and that the mechanism was derived from the activation of p53
      and the p53 pathway. It was also surprising that L2 showed high antiproliferation
      effect against p53 null HL60 cells, which was quite different from nutlin-1. G2/M
      phase arrest might have contributed to the high antiproliferation activity of L2
      on HL60 cells. The changes of p53 and MDM2 protein levels in L2-treated HL60
      cells indicated that the mechanisms involved in the cell cycle arrest in A549 and
      HL60 cells were probably different, to which our future research would be
      devoted.

PMID- 19579267
TI  - The role of own-body representations in action observation: a functional MRI
      study.
AB  - Does own-body information matter during the observation of another person? Using
      functional MRI, we sought to determine whether incompatibility between observed
      hand movements and the observer's hand posture leads to differential neural
      activation compared with compatibility. Twenty participants were asked to observe
      videos of human hand movements while their hand was placed in a compatible or an
      incompatible posture. Subsequently, they performed motor imagery of the observed
      movement. Conjunction analysis of both observation conditions revealed activation
      in the ventral premotor cortex and the inferior parietal cortex. Observing
      movements with incompatible hand position elicited higher activation in the left
      dorsolateral prefrontal cortex and the inferior parietal cortex of both
      hemispheres. These findings suggest a tight interplay between body
      representations and action observation.

PMID- 19579268
TI  - Neuropeptide Y infusion into the shell region of the rat nucleus accumbens
      increases extracellular levels of dopamine.
AB  - Increases in extracellular dopamine in the shell region of the nucleus accumbens
      are centrally involved in mediating reinforcement of addictive drugs.
      Neuropeptide Y (NPY) and its receptors are present in the nucleus accumbens and
      have been implicated in addiction mechanisms. This study further explored the
      potential role of NPY in addiction mechanisms using microdialysis to measure
      extracellular dopamine in vivo after infusion of NPY directly into the accumbal
      shell region of adult rats. NPY was found to dose-dependently increase
      extracellular dopamine levels, indicating that NPY could play an important role
      in drug reinforcement by modulating accumbal dopamine levels

PMID- 19579269
TI  - Additive effect of cyclooxygenase and nitric oxide synthase blockade on the
      cerebrocortical microcirculation.
AB  - The contribution of vasodilator cyclooxygenase (COX) metabolites to the
      maintenance of the cerebrocortical blood flow (CBF) has been studied under
      physiological conditions and in nitric oxide (NO) deficiency. Inhibition of COX
      decreased resting CBF without changing arterial blood pressure. NO synthase
      blockade resulted in hypertension and CBF reduction as well as in enhanced
      cerebral prostacyclin and prostaglandin E2 production. Despite the increased
      vasodilator prostanoid release in the absence of NO, the CBF-decreasing effect of
      COX blockade failed to increase. Therefore, the COX pathway seems to play a
      similar role under physiological and NO-deficient conditions in the maintenance
      of the resting CBF.

PMID- 19579270
TI  - Inverse association of repressor growth factor independent-1 with CD8 T cell
      interleukin (IL)-7 receptor [alpha] expression and limited signal transducers and
      activators of transcription signaling in response to IL-7 among [gamma]-chain
      cytokines in HIV patients.
AB  - BACKGROUND: CD8 T lymphocytes from chronically infected HIV-positive patients
      degenerate into a preapoptotic state and exhibit impaired functionality.
      Particularly in viremic patients, this was associated with an increased
      proportion of interleukin-7 receptor-alpha low-expressing (IL-7Ralpha(low))
      effector-like CD8 T cells. As cytokine signaling through signal transducers and
      activators of transcription (STAT) is essential for cellular function, we
      hypothesized that activation of this pathway may be impaired in these cells.
      OBJECTIVES: To evaluate cytokine-induced STAT activation in IL-7Ralpha(low) and
      IL-7Ralpha(high) CD8 T cells from chronically infected HIV-positive patients and
      investigate the potential molecular mechanism involved in the reduced IL-7Ralpha
      expression. METHODS: CD8 T cells from HIV-positive patients on and off
      antiretroviral therapy were assayed respectively for STAT activation, cytokine
      receptor, and transcription factor expression by flow cytometry and real-time
      PCR. RESULTS: IL-7 stimulation failed to activate STAT5 in a substantial
      proportion of patient CD8 T cells. This correlated with reduced IL-7Ralpha mRNA
      and surface protein expression. Interestingly, IL-7Ralpha(low) cells appeared to
      be fully capable of recruiting the STAT pathway in response to IL-2, IL-4, IL-10,
      and IL-15. mRNA expression suggested a potential role for growth factor
      independent (Gfi)-1 as an IL-7Ralpha transcriptional repressor, but not that of
      other transcriptional regulators studied, including Gfi-1B and GA-binding protein
      alpha. Programmed death-1 inhibitory receptor, though upregulated in CD8 T cells
      from HIV-positive patients, appeared unrelated to IL-7Ralpha expression and STAT
      signaling capacity.

PMID- 19579271
TI  - Glucose control in critically ill patients.

PMID- 19579272
TI  - Glucose control in critically ill patients.

PMID- 19579273
TI  - Glucose control in critically ill patients.

PMID- 19579274
TI  - Glucose control in critically ill patients.

PMID- 19579275
TI  - Glucose control in critically ill patients.

PMID- 19579276
TI  - Proceedings of the first formal meeting of the International Society for Hepatic
      Encephalopathy and Nitrogen Metabolism. May 2008. Padua, Italy.

PMID- 19579277
TI  - Rosuvastatin in patients undergoing hemodialysis.

PMID- 19579278
TI  - Rosuvastatin in patients undergoing hemodialysis.

PMID- 19579279
TI  - Cetuximab for metastatic colorectal cancer.

PMID- 19579280
TI  - Cetuximab for metastatic colorectal cancer.

PMID- 19579281
TI  - Cetuximab for metastatic colorectal cancer.

PMID- 19579282
TI  - Moyamoya disease and moyamoya syndrome.

PMID- 19579283
TI  - Renal disease in minority populations and developing nations. Proceedings of a
      satellite meeting of the World Congress of Nephrology. April 25-27, 2007.
      Petropolis, Brazil.

PMID- 19579284
TI  - Cardiovascular research in Turkey.

PMID- 19579285
TI  - [Direct hearing aid provision by ENT specialists: Recommendations for prevention
      and treatment of complications after taking ear impressions].
AB  - In times of budgeting, rising costs and monetary losses, an increasing number of
      ENT specialists considers the hearing system sector due to the distinct
      undersupply and the expected demographic development to be a market of the future
      and appropriate to enlarge their field of competence. Exact prevalence of direct
      hearing aid provision by German otorhinolaryngologists as well as its
      complication rate are not well-known. Retrospectively, all patients were
      evaluated who presented at our department with complications in the context of
      outpatient direct hearing aid supply within the last 3 years. Inappropriate
      fitting contains the danger of malformed or displaced ear impressions with
      various injury patterns comprising the external auditory canal, tympanic membrane
      and ossicular chain. Practical advices for prevention of complications include
      the accurate modeling and placement of sufficient impression pads behind the
      second bend of the auditory canal, using an adequate type of impression material
      as well as performing the correct application procedures. Recommendations for
      diagnostic patterns and treatment of complications after taking ear impressions
      are presented, the differences between German "traditional" and "direct" hearing
      aid provision are critically discussed.

PMID- 19579286
TI  - Cytokines and schizophrenia: Microglia hypothesis of schizophrenia.
AB  - The etiology of schizophrenia remains unclear, while there has been a growing
      amount of evidence for the neuroinflammation and immunogenetics, which are
      characterized by an increased serum concentration of several pro-inflammatory
      cytokines. Despite the fact that microglia comprise only <10% of the total brain
      cells, microglia respond rapidly to even minor pathological changes in the brain
      and may contribute directly to the neuronal degeneration by producing various pro
      inflammatory cytokines and free radicals. In many aspects, the neuropathology of
      schizophrenia has recently been reported to be closely associatedwith microglial
      activation. Previous studies have shown the inhibitory effects of some
      typical/atypical antipsychotics on the release of inflammatory cytokines and free
      radicals from activated microglia, both of which have recently been known to
      cause a decrease in neurogenesis as well as white matter abnormalities in the
      brains of patients with schizophrenia. The microglia hypothesis of schizophrenia
      may shed new light on the therapeutic strategy for schizophrenia.

PMID- 19579287
TI  - Resolved: Targeting a higher hemoglobin is associated with greater risk in
      patients with CKD anemia: con.

PMID- 19579288
TI  - Isolation and characterization of resident mesenchymal stem cells in human
      glomeruli.
AB  - In humans, renal resident stem cells were identified within the interstitium, the
      tubular cells, and the Bowman's capsule. The aim of the present study was to
      investigate whether multipotent stem cells are present also in the adult human
      decapsulated glomeruli and whether they represent a resident population. We found
      that human glomeruli deprived of the Bowman's capsule contain a population of
      CD133+CD146+ cells and a population of CD133-CD146+ cells expressing mesenchymal
      stem cell (MSC) markers and renal stem cell markers CD24 and Pax-2. The
      CD133+CD146+ cells differed from those previously isolated from Bowman's capsule
      as they co-expressed endothelial markers, such as CD31 and von Willebrand factor
      (vWF), were CD24-negative and were not clonogenic, suggesting an endothelial
      commitment. The glomerular mesenchymal CD133-CD146+ population (Gl-MSC) exhibited
      self-renewal capability, clonogenicity, and multipotency. In addition to
      osteogenic, adipogenic, and chondrogenic differentiation, these cells were able
      to differentiate to endothelial cells and epithelial cells expressing podocytes
      markers such as nephrin, podocin, and synaptopodin. Moreover, Gl-MSC when
      cultured in appropriate conditions, acquired mesangial cell markers such as alpha
      smooth muscle actin (alpha-SMA) and angiotensin II (AT-II) receptor I. The
      expression of the embryonic organ-specific PAX-2 gene and protein and of donor
      sex identity when isolated from glomeruli of a renal allograft suggested these
      cells to be a tissue resident population. In conclusion, these results indicate
      the presence of a multipotent mesenchymal cell population resident in human
      glomeruli that may have a role in the physiological cell turnover and/or in
      response to glomerular injury.

PMID- 19579289
TI  - Divergent effects of cell environment on HIV entry inhibitor activity.
AB  - OBJECTIVE: Successful HIV vaccine and entry inhibitor development depends on use
      of assay systems that closely reflect in-vivo activities. Recent reports suggest
      that the currently most widely used assay format, which relies on the genetically
      engineered target cell line TZM-bl, can fail to detect certain neutralization
      activities detected on primary peripheral blood mononuclear cell (PBMC)-based
      assay systems. In the present study, we investigate the influence the target cell
      context bears on HIV entry inhibition. DESIGN: In a comprehensive survey, the
      effect of 11 neutralizing antibodies and inhibitors in blocking entry of 30
      envelope pseudotyped virus strains in two types of target cells, PBMC and TZM-bl,
      was evaluated. METHODS: Env-pseudotyped HIV infection of PBMC and TZM-bl cells.
      RESULTS: We demonstrate here that depending on the type of inhibitor, relative
      neutralization potencies are shifted to a variable extent and direction on TZM-bl
      and PBMC cells. In our assay set up, differences in inhibitor activity were
      solely effected by the target cell environment and amounted up to 2-3 logs lower
      activity on TZM-bl cells in several cases. Overall, neutralizing antibodies,
      2G12, 2F5 and 4E10, were less active in the TZM-bl system, whereas CD4 binding
      site directed inhibitor activities were detected equally well on both target
      cells, raising concerns that the TZM-bl assay may overrate the relevance of CD4
      binding site specific responses. CONCLUSION: Our data strongly argue that
      preclinical assessment should not be restricted to a single type of assay, as
      systematic underestimation or overestimation of activities would be inevitable.

PMID- 19579291
TI  - Venous thromboembolism: from bench to bedside. Proceedings of a symposium.
      September 11-13, 2008. Chapel Hill, North Carolina, USA.

PMID- 19579292
TI  - Unprotected sex between HIV-infected partners keeps immune responses activated.

PMID- 19579290
TI  - A situation update on HIV epidemics among people who inject drugs and national
      responses in South-East Asia Region.
AB  - We explore the magnitude of and current trends in HIV infection among people who
      inject drugs and estimate the reach of harm reduction interventions among them in
      seven high-burden countries of the South-East Asia Region. Our data are drawn
      from the published and unpublished literature, routine national HIV serological
      and behavioural surveillance surveys and information from key informants. Six
      countries (Thailand, Myanmar, Nepal, Indonesia, India, and Bangladesh) had
      significant epidemics of HIV among people who inject drugs. In Thailand,
      Indonesia, Bangladesh, Myanmar and India, there is no significant decline in the
      prevalence of HIV epidemics in this population. In Nepal, north-east India, and
      some cities in Myanmar, there is some evidence of decline in risk behaviours and
      a concomitant decline in HIV prevalence. This is countered by the rapid emergence
      of epidemics in new geographical pockets. Available programme data suggest that
      less than 12 000 of the estimated 800 000 (1.5%) people who inject drugs have
      access to opioid substitution therapy, and 20-25% were reached by needle-syringe
      programmes at least once during the past 12 months. A mapping of harm reduction
      interventions suggests a lack of congruence between the location of established
      and emerging epidemics and the availability of scaled-up prevention services.
      Harm reduction interventions in closed settings are almost nonexistent. To
      achieve significant impact on the HIV epidemics among this population,
      governments, specifically national AIDS programmes, urgently need to scale up
      needle-syringe programmes and opioid substitution therapy and make these widely
      available both in community and closed settings.

PMID- 19579293
TI  - The Medicines Company: an emerging   pharmaceutical company in cardiology is  
      spearheading an innovative approach to critical   care medicines.

PMID- 19579294
TI  - Role of roasting conditions in the profile of volatile flavor chemicals formed
      from coffee beans.
AB  - The volatile chemicals in dichloromethane extracts from green coffee beans,
      roasted at 230 degrees C for 12 min (light), at 240 degrees C for 14 min
      (medium), at 250 degrees C for 17 min (city), or at 250 degrees C for 21 min
      (French), were analyzed by gas chromatography and gas chromatography-mass
      spectrometry. Among the 52 volatile compounds identified, the major compounds
      were 5-hydroxymethylfurfural, furfuryl alcohol, and 6-methyl-3,5-dihydroxy-4H
      pyran-4-one in light-roasted beans; furfuryl alcohol, 5-hydroxymethylfurfural,
      and gamma-butyrolactone in medium-roasted beans; furfuryl alcohol, gamma
      butyrolactone, and 2-acetylpyrrole in city-raosted beans; and gamma
      butyrolactone, furfuryl alcohol, and catechol in French-roasted beans. Furfural
      derivatives and furanones were yielded in relatively high concentrations under
      mild roasting conditions and then reduced at higher roasting intensities. More
      pyridines and pyrroles were formed by high roasting intensities than by mild
      roasting intensities. Chlorogenic acid degradation products, phenols, and a
      lactone were produced more by high roasting intensities than by low roasting
      intensities. The results of the present study suggest that controlling the
      roasting conditions according to the formation of particular chemicals can
      prepare a roasted coffee with preferable flavor.

PMID- 19579295
TI  - Resolved: Targeting a higher hemoglobin is associated with greater risk in
      patients with CKD anemia: pro.
AB  - Some time has passed since the torrent of discussion surrounding the
      cardiovascular risk of pushing up hemoglobin concentrations in dialysis patients
      with erythropoietin. The debate here reflects a look back on the tension produced
      by confusing data and outcomes. Is it the target hemoglobin per se or the high
      doses of erythropoietin in subsets of resistant patients that is the problem? You
      decide.

PMID- 19579296
TI  - Translating new insights into treatment optimisation in multiple sclerosis.
      Proceedings of the Seventh International Symposium on Multiple Sclerosis. May 23
      24, 2008. Vienna, Austria.

PMID- 19579297
TI  - Use of webcam as arthroscopic training  model for junior surgical trainees.

PMID- 19579298
TI  - A variable angled drill guide for acetabular screw insertion in total hip
      replacement.

PMID- 19579299
TI  - A helpful technique for removing resurfacing acetabular components.

PMID- 19579300
TI  - A technique for applying a non-adherent, tri-laminate dressing for hypospadias
      repair.

PMID- 19579301
TI  - L-configuration re-attachment of distal biceps tendon rupture.

PMID- 19579302
TI  - Laser avulsion.

PMID- 19579303
TI  - 'A close shave' -- use of a disposable razor blade in the management of
      rhinophyma.

PMID- 19579304
TI  - Improvised stone extractor in laparoscopic cholecystectomy.

PMID- 19579305
TI  - 'Mercedes' incision -- another oncoplastic technique for excision of breast
      tumours.

PMID- 19579306
TI  - A technique for the removal of the distal part of a broken intramedullary nail.

PMID- 19579307
TI  - The use of an axillary crutch as a knee flexion contracture correction device.

PMID- 19579308
TI  - Ask the doctor.  When I am under great stress, my blood pressure sometimes shoots
      up to 200/120 for a short time but then quickly goes down to 120/80 or lower and
      stays there.  One doctor told me that spikes like these are normal and not to
      worry about them.  Another told me this isn't normal or healthy.  Who is right?

PMID- 19579309
TI  - Statins, aspirin affect prostate cancer test.

PMID- 19579311
TI  - Beware cardiac arrest after heart attack.

PMID- 19579310
TI  - Trial gives nod to home warfarin monitoring.

PMID- 19579312
TI  - C+E get an F for heart protection.

PMID- 19579314
TI  - Exercise is key to low back pain prevention. Strengthen your core muscles to
      enhance physical function.

PMID- 19579313
TI  - Ask the doctor.  Can muscle damage from a statin, or from strenuous exercise,
      elevate creatinine even after I stopped taking the statin and exercising but
      continue to take Zetia and Diovan HCT?

PMID- 19579315
TI  - Aspirin for heart attack, stroke prevention. When benefits outweigh risks: four
      new studies help clarify who should--and who shouldn't--take the drug.

PMID- 19579316
TI  - Elevated blood sugar levels lower brain function in diabetics.  The effects of
      diet on your blood glucose levels can diminish memory and other cognitive skills.

PMID- 19579317
TI  - I've read that fish oil is effective as a pain killer for rheumatoid arthritis
      (RA), and I know several people who suffer from RA and have found fish oil
      supplements effective.  So far, I've been taking them for three months to relieve
      RA pain in my hands and have noticed no difference.  Do these supplements really
      work?

PMID- 19579319
TI  - I have shingles and my doctor has prescribed a tricyclic antidepressant for me.
      I'm not at all depressed, so I don't understand why I should have to take this
      medication. Is depression connected to shingles?

PMID- 19579318
TI  - My doctor suggested I undergo an electromyography.  What is this test and why do
      I need it?

PMID- 19579320
TI  - A few months ago I had coronary artery bypass surgery.  I still have swelling in
      my legs around the incisions.  Is this normal?

PMID- 19579322
TI  - Headache: when to worry, what to do.

PMID- 19579321
TI  - Finasteride to prevent prostate cancer: a new chapter.

PMID- 19579323
TI  - Soy and sperm.

PMID- 19579324
TI  - On call.  My father has had two surgeries in the past year to remove calcium
      deposits in his prostate.  Is there any way to avoid this buildup, or will it
      continue?

PMID- 19579327
TI  - Beyond Darwin: the future of molecular biology.

PMID- 19579326
TI  - Monthly report on dracunculiasis   cases, January-May 2009.

PMID- 19579325
TI  - Progress towards the 2012 measles elimination goal in WHO's Western Pacific
      Region, 1990-2008.

PMID- 19579328
TI  - [Surgery of glioma].

PMID- 19579329
TI  - [Intelligent operating room for surgery of glioma].

PMID- 19579330
TI  - [Central nervous system glioma. Multi-drug chemotherapy including temozolomide].

PMID- 19579331
TI  - [Angiogenesis suppressing therapy applied to malignant glioma].

PMID- 19579332
TI  - [Society news].

PMID- 19579333
TI  - An Ottoman observer of central European surgery in the middle of the seventeenth
      century.
AB  - Evliya Celebi, a famous Ottoman traveller of the mid seventeenth century, has
      left us a written account of the places he visited in central Europe. This paper
      discusses operations that he claimed to have witnessed in Vienna in 1665, the
      most extraordinary of which was an example of neurosurgery, and it examines what
      his description tells us about perceptions and images of medicine. His
      impressions of central European medicine, as viewed by a Muslim from the east,
      offer a perspective so far little studied.

PMID- 19579334
TI  - Robert Dyer Lyons (I 826-1886), microscopist, meteorologist, physician,
      parliamentarian.
AB  - When the attention of Robert Dyer Lyons was drawn to the medical value of the
      microscope in 1850, he trained himself in its use, and after annually reviewing
      its recent discoveries he was despatched as chief pathologist to the Army of the
      East in April 1855. His Report (1856) was a feather in his cap when he returned
      from the Crimea to Dublin and took up a professorship in the recently founded
      Catholic University medical school. Popularity as a teacher and success as a
      physician broadened his interests to national affairs, and he advocated increased
      funding for university education and re-afforestation. He was elected a Liberal M
      P for Dublin in 1880 but did not stand for re-election in 1886, the year of his
      death.

PMID- 19579335
TI  - An unknown treasure in Brugge (Bruges): the oldest portrait of Andreas Vesallius
      on a stained glass window.
AB  - Four iconographic pictures of Andreas Vesalius on glass painted windows, in
      Rochester, Minnesota, USA; Leuven (Louvain, Belgium); Saint Paul, Minnesota, USA;
      and Innsbruck (Austria), were made in the period between 1943 and 1956. Recently,
      we have found in Brugge (Bruges) a much older portrait of Vesalius, in the form
      of a medallion on glass. It was painted between 1860 and 1870 by Samuel Coucke
      who had been commissioned by Dr. Francois Vanden Abeele for the decoration of his
      medical office.

PMID- 19579336
TI  - Marinos Gerulanos (1867 - 1960): charismatic Greek, surgeon, humanist and
      benefactor.
AB  - Marinos Gerulanos, who was a Professor of Surgery and President of the Academy of
      Athens, was one of the most prominent of Greek surgeons. He made major
      contributions to the treatment of disease, to the organization of nursing and to
      medical education in Greece in the first half of the twentieth century.

PMID- 19579337
TI  - [Gil Eannes--the hospital ship of the Portuguese fishing fleet].
AB  - The history of Portuguese hospital-ships dates back to the fleets in the era of
      the Great Discoveries. In 1916, during the First World War, the Allies appealed
      to Portugal to act as a neutral country. All the German ships on the river Tagus
      were impounded and adapted for tasks related to the war. The Hanseatic line
      vessel Lahneck had its name changed to Gil Eannes and was modified for troop
      transport and to give assistance to fishing boats. Many years later, when the old
      Gil Eanes came to the end of its life and needed to be replaced, a new ship was
      built in the Viana do Castelo shipyard, using up-to-date designs for a hospital
      ship. The new ship was launched in 1955, mainly to assist the Portuguese cod fish
      fleet, working in the seas around Newfoundland. More recently, it has returned to
      Viana do Castelo docks and, after restoration, has been transformed into a
      nautical museum and a student residence, to keep alive the memories of this
      traditional Portuguese fishermen's activity.

PMID- 19579338
TI  - [The elderly and surgery in the Middle Ages].
AB  - Until the end of the nineteenth century, the elderly were considered to be high
      risk patients, on whom surgeons wishing to preserve their reputation should not
      operate. A study of the works of four medieval surgeons, Paul ofAegina, Henri de
      Mondeville, Guillaume de Salicet and Guy de Chauliac, discloses few references to
      the elderly. Despite risks associated with their fragile constitution and their
      age, it seems that such patients did at times undergo surgery. Bleeding was not
      used for patients over 70 years of age and dosage of drugs was also adjusted for
      age. Attempts to modify the signs of old age were probably an important and
      lucrative part of surgical activity.

PMID- 19579339
TI  - [ Dentistry during the American Civil War (1861-1865)].
AB  - During the American Civil War, military surgery developed rapidly and underwent
      great expansion. The same happened in military journalism and in photography and
      through these media came epic stories of the famous hospitals and the surgeons,
      who were completely committed to the care of the wounded. Dental surgery and
      maxillofacial surgery expanded despite clear organisational deficiencies within
      the two armies and the fact that both specialties were still in their early
      stages. This article considers some of the important and distinguished figures in
      the two disciplines.

PMID- 19579340
TI  - A possible early description of nystagmus and photophobia in albinism.
AB  - It is recognized today that albinism is accompanied by a cohort of ophthalmic and
      neuro-ophthalmic problems. These may not always be as obvious to the casual
      observer as the lack of pigment in the eyebrows, hair, or skin, and thus early
      descriptions of this rare genetic condition may have initially focused on the
      unusual colour of the hair, skin, or eyebrows and not the eye-related problems.
      While it is not easy to find an accurate ancient description of albinism, we here
      propose that a Talmudic account from over 1500 years ago may possibly be
      describing nystagmus and photophobia in albinism in a population which resided
      along the River Tigris.

PMID- 19579341
TI  - The statues of Andreas Vesalius: 'a capite ad calcem'.
AB  - The number of statues of Vesalius, fully depicting the father of anatomy, is very
      limited world-wide. What follows is a summary and description of the statues in
      Brussels,Vienna, Leuven (Louvain), and Chicago. The three-dimensional
      representation of Vesalius's first 'muscle man' in Terneuzen is also included.

PMID- 19579342
TI  - The art in Abel Salazar's life (1889-1946)--a Portuguese Renaissance spirit of
      the twentieth century.
AB  - Abel Salazar was a true renaissance spirit, scientist, doctor, humanist, artist
      and writer. His paintings combined realism with a very strong social sense. This
      article looks at his art and the influence that he had through it on his
      contemporaries.

PMID- 19579344
TI  - [The plague of the third pandemic and its current remergence].
AB  - The reappearance of the plague in the 19th century, in what is generally referred
      to as the third pandemic, brought back painful memories of the great plague
      outbreaks of the past that had killed tens of millions of people. At the same
      time, this new pandemic opened the era of great discoveries, such as
      identification of the Yersinia pestis bacterium, of transmission vectors and the
      first effective treatments. With these advances it became possible to control a
      disease which had, because of progress in maritime transport, spread almost
      throughout the world.

PMID- 19579343
TI  - [Discussion of a medical officer carrying the arm-band of the Red Cross during
      the second world war].
AB  - Sacrificing his life to save that of his soldiers and of his nursing staff,
      Captain Ben Salomon became a legend. Yet, studies of international treaties and
      of some directives specific to the American Army have seriously held back the
      historical and public recognition of his heroism. Indeed, when he took hold of
      the machine gun to cover his men's retreat in 1944, he was wearing a Red Cross
      armband and was enlisted as a "doctor". What did this mean exactly? Was his
      action a misdemeanor or definitely an act of heroism?

PMID- 19579345
TI  - [The doctor-patient relationship in the novel Thibault].
AB  - A masterpiece of the realistic novel, Les Thibault is a document of political and
      social life before and during the First World War. At the same time, it is a
      document of the status of medicine at the beginning of the 20th century. Roger
      Martin du Gard collected information on the diseases of the time, on medical
      deontology and on the doctor-patient relationship which is established during the
      medical encounter. The novel reflects the author's ability to transform a
      document into literary fiction. Antoine Thibault, who represents the ideal
      doctor, is able to create a perfect relationship with his patients, basing this
      on confidence. He also provides one of the literary models of a doctor practicing
      medicine from a sense of vocation.

PMID- 19579346
TI  - [The three lives of the Count de Bonneval, alias Osman Pasha (1675-1747)].
AB  - Count Claude-Alexandre de Bonneval (1675-1747), had a unusual existence: he had
      three consecutive lives: as an Officer in the Royal Guard of Louis XIV, as Major
      General with Prince Emmanuel of Savoy and, finally, as Ottoman Pasha in
      Constantinople. He was a man of multiple facets: soldier and political adviser,
      swordsman and world traveller, friend of Casanova, Fenelon, Montesquieu and
      Leibniz. He was also an inveterate transgressor of every rule and, in the end, a
      renegade apostate. Many explanations have been offered for his astounding life:
      plain aristocratic frivolity, emotional instability, and possibly, in reference
      to a permanent quest for new adventures, countries or religions, a touch of
      transformism. Obviously, Bonneval concealed, behind a flamboyant personality,
      some sort of psychiatric fragility which might suggest, in retrospect, a
      "paranoid syndrome" but, certainly, no trace of what is common in psychopathic
      patients, a weariness of life. Bonneval loved each one of his three lives and the
      feeling was mutual.

PMID- 19579347
TI  - [The useless pain].

PMID- 19579348
TI  - [Defeat pain?].

PMID- 19579349
TI  - [Greek and christian response to suffering].

PMID- 19579350
TI  - Progress, public health, and power: Foucault and the Homemakers' Clubs of
      Saskatchewan.
AB  - From 1911 to 1979, the Homemakers' Clubs of Saskatchewan mobilized and monitored
      extensive study and action in the field of public health. This article explores
      how these clubs exhorted women to strive for progress, and encouraged women to
      internalize such striving as fundamental to their own identities. The techniques
      used included encouraging commitment to shared goals, making such goals personal,
      structuring action, requiring women to report their thoughts and actions,
      rewarding certain behaviors, and linking those behaviors with emotionally
      compelling causes. Rooted in a Foucauldian conceptual framework, this article
      contributes to the sociological understanding of subject formation and
      governance.

PMID- 19579351
TI  - Sterilization in Alberta, 1928 to 1972: gender matters.
AB  - Alberta, Canada, passed a Sexual Sterilization Act in 1928 and up until its
      repeal in 1972, over 2,800 people were sterilized. Women were overrepresented in
      the number of sterilizations performed. This paper explores how changing
      understandings of eugenics led to a subtle transformation which resulted in a
      "two-pronged" system that targeted mentally defective men, often a danger to
      society, and mentally normal but morally abnormal women who consented to
      sterilization. The end result was success for the movement in terms of the types
      and numbers of people sterilized, and in the longevity of the program.

PMID- 19579352
TI  - Individual and community factors affecting psychological sense of community,
      attraction, and neighboring in rural communities.
AB  - One thousand nine hundred ninety-five individuals in 20 rural Canadian
      communities were measured on perceived social cohesion by the three Buckner scale
      subdimensions: psychological sense of community (PSOC), attraction, and
      neighboring. Number of household children, income over $20,000, age, birthplace
      in, and years lived in the community significantly positively influenced PSOC and
      Attraction. Number of household children (positive for income over $20,000;
      otherwise negative), income over $40,000, birthplace, and years in the community
      significantly influenced neighboring. Increased interaction generally increases
      individuals' social cohesion. As the only significant community variable was
      being on an island province, individual-oriented policies are recommended to
      increase cohesion.

PMID- 19579353
TI  - Toward an ethnography of silence: the lived presence of the past in the everyday
      life of Holocaust trauma survivors and their descendants in Israel.
AB  - Despite the abundant scholarship on posttraumatic stress disorder (PTSD) and the
      memoropolitics entailed by testimonial accounts of trauma and genocide, little is
      known of the everyday experience of trauma survivors and their descendants.
      Survivor silence is thought to signify only psychological or political repression
      and the "unspeakability" of traumatic pasts. It is widely accepted that the
      everyday lives of trauma victims and their descendants entail only the "absence
      of presence" of the past and the absence of descendant knowledge of that past,
      while the familial social milieu is thought to foster only the wounds of
      transmitted PTSD. Contrary to the literature, ethnographic accounts of Holocaust
      descendants depict the survivor home as embedding the nonpathological presence of
      the Holocaust past within silent, embodied practices, person-object interaction,
      and person-person interaction. These silent traces form an experiential matrix of
      Holocaust presence that sustains familial "lived memory" of the past and
      transmits tacit knowledge of the past within the everyday private social milieu.
      The ethnography of silent memory may also provide a tentative model of
      nontraumatic individual and familial memory work in everyday life.

PMID- 19579354
TI  - Finding the way: a critical discussion of anthropological theories of human
      spatial orientation with reference to reindeer herders of northeastern Europe and
      western Siberia.
AB  - In anthropology, research on human spatial orientation (wayfinding) has centered
      on two conflicting theories: the "mental map," whereby humans build abstract
      cognitive representations of the spatial relations between objects, and
      "practical mastery," which rejects the idea that such abstract representations
      exist and, in its most developed form, suggests that wayfinding is a process of
      moving from one recognized visual perspective (vista) to another (transitions
      between vistas). In this paper we reveal, on the basis of existing psychology and
      geography research, that both wayfinding theories are in fact complementary:
      humans rely on mental maps but also memorize vistas while navigating, and an
      individual's navigation method, ability, and the form of the mental map is likely
      to depend on a situation as well as on factors such as age, sex, familiarity with
      the environment, and life history. We demonstrate (using research material
      obtained during fieldwork carried out among Komi and Nenets reindeer herders)
      that anthropology can contribute to human spatial cognitive research, which has
      traditionally been an interdisciplinary endeavor, by identifying differences in
      spatial representation between different people and peoples. However, future
      contributions can be achieved only if anthropologists accept that mental maps and
      route knowledge (as advocated by practical mastery) are part and parcel of
      spatial cognition.

PMID- 19579355
TI  - Why do men hunt? A reevaluation of "man the hunter" and the sexual division of
      labor.
AB  - The role of men in hunter-gatherer societies has been subject to vigorous debate
      over the past 15 years. The proposal that men hunt wild game as a form of status
      signaling or "showing off" to provide reproductive benefits to the hunter
      challenges the traditional view that men hunt to provision their families. Two
      broad assumptions underlie the signaling view: (1) hunting is a poor means of
      obtaining food, and (2) hunted game is a public good shared widely with others
      and without expectation of future reciprocation. If hunters lack the ability to
      direct food shares and obtain subsequent benefits contingent on redistribution,
      then the ubiquitous observations of male hunting and universal pair-bonding
      cannot be explained from a perspective that emphasizes kin provisioning and a
      division of labor. Here we show that there is little empirical support for the
      view that men hunt for signaling benefits alone. The ethnographic record depicts
      a more complex relationship between food sharing patterns, subsistence
      strategies, mating, and the sexual division of labor. We present a framework
      incorporating trade-offs between mating and subsistence strategies in an economic
      bargaining context that contributes to understanding men's and women's roles in
      hunter-gatherer societies.

PMID- 19579356
TI  - Unlikely alliances: encounters between state science, nature spirits, and
      indigenous industrial forestry in Mexico, 1926-2008.
AB  - Indigenous community leaders and conservationists in Oaxaca, Mexico, believe that
      deforestation causes streams to dry up and threatens rainfall, authorizing
      popular mobilizations against industrial logging. This belief was produced by a
      combination of indigenous beliefs in nature spirits and early-twentieth-century
      state-sponsored desiccation theory, which was brought to the Valley of Mexico in
      the 1920s. Desiccation theory acquires political significance because it allows
      rural people to build political and epistemic alliances that bypass industrial
      forestry institutions and find sympathetic urban audiences and environmentalist
      allies, undermining state claims to reason and scientific authority. These
      alliances require the skillful translation and mistranslation of local
      environmental concerns by activists and conservationists, who link the concerns
      of urban audiences with those of rural people. Popular beliefs about climate and
      forests in Mexico structure the authority and credibility of the state and will
      powerfully affect efforts to protect forests to mitigate climate change.

PMID- 19579357
TI  - Humphry Davy and the Royal Institution of Great Britain.
AB  - The abortive attempts of Sir Humphry Davy to introduce modest reforms at the
      Royal Society of London during his Presidency (1820-27) contrast with his
      (largely unstudied) earlier experience of administration at the Royal Institution
      of Great Britain (RI). Davy's attempts to combat the systemic weaknesses in
      governance and funding, and his role in effecting changes at the RI, in
      association with a core group of reformers, merit consideration. This paper
      analyses important aspects of the early management and social structure of the RI
      and examines the inner workings of the institution. It shows how and why the
      Library, its most valuable financial asset, and its celebrated Laboratory,
      developed along distinctive lines, each with its own support structures and intra
      institutional interests. While acknowledging the roles traditionally ascribed to
      Count Rumford and Sir Joseph Banks, the paper highlights the contributions of
      other early patrons such as Thomas Bernard, son of a colonial governor of
      Massachusetts, and Earl Spencer, a leading European bibliophile and RI President
      from 1813 to 1825. The promotion of a Bill in Parliament in 1810, designed to
      transform the RI from a proprietary body politic into a corporation of members,
      and the subsequent framing of the bye-laws, provided opportunities to establish a
      more democratic structure of elected committees for the conduct of science.

PMID- 19579358
TI  - 'Where are your intelligent mothers to come from?': marriage and family in the
      scientific career of Dame Kathleen Lonsdale FRS (1903-71).
AB  - Although she was one of the most successful female scientists in twentieth
      century Britain, the X-ray crystallographer Kathleen Yardley Lonsdale (1903-71)
      has received relatively little attention from historians of science. This paper,
      based on material from the recently opened Dame Kathleen Lonsdale Papers, argues
      that Lonsdale's scientific career was shaped in particular ways by her identity
      not just as a woman, but as a married woman and a mother. When interacting with
      her scientific colleagues, Lonsdale frequently had to confront the assumption
      that married women should not pursue scientific careers, an attitude shaped by
      British concerns about reasserting traditional gender roles after the World Wars
      I and II. Furthermore, although Lonsdale's husband, Thomas, was an ardent
      supporter of her career, in the early 1930s Lonsdale left research temporarily to
      care for her small children. Her desire to work from home during this period led
      her to pursue one of her most significant scientific projects: the creation of
      crystallographic reference tables. Lonsdale's own experiences, and those of her
      female students, led her to focus on issues of marriage and family when she began
      speaking and writing about women in science during the late 1960s.

PMID- 19579359
TI  - The history of science in Spain. A critical overview.
AB  - This paper analyses how the history of science evolved as an academic discipline
      in Spain throughout the twentieth century. It attempts to identify the kind of
      questions, historical periods, and subjects that were scrutinized and the kind of
      domestic and international influences that shaped historians' work. The article
      also devotes to longstanding public debates such as the commonly accepted thesis
      of the lack of a solid scientific culture over the past two centuries and its
      influence on the ways of writing the history of science. It aims to discuss how
      new trends from international mainstream historiography can be appropriated by
      local scholars, and how new questions and new research agendas have emerged in
      recent decades. The paper also integrates some relevant contributions to the
      historiography of Spanish science made by non-Spanish scholars.

PMID- 19579360
TI  - Perspectives on contemporary history of science in Portugal.
AB  - The task of writing about historiography of science in a European periphery such
      as Portugal is particularly difficult due to the unavailability of a systematic
      inventory of sources for the history of science. In this paper we select a group
      of 20th-century sources, having in view the extended timeline available to the
      sorts of questions which can be posed to the historical material. We opted to
      analyze representative probes for four different categories of sources: a journal
      (1937-1951); the proceedings of a congress organized in the context of a
      commemorative event (1940); the works of two historians of science (1950s
      onward); and finally commemorative volumes celebrating the anniversary of the
      Academy of Sciences of Lisbon (1986, 1992). Besides briefly describing authors'
      profiles, professional backgrounds, historical periods and scientific areas
      covered, we discuss the type of historical account produced. We conclude with a
      brief overview of the state of the discipline in the past fifteen years bearing
      in mind historiographical orientations.

PMID- 19579361
TI  - Origins of the historiography of modern Greek science.
AB  - The purpose of the paper is to examine how Greek historians account for the
      presence of modern scientific ideas in the intellectual environment of eighteenth
      century Greek-speaking society. It will also discuss the function of the history
      of modern Greek science in the context of Greek national historiography. As will
      be shown, the history of modem Greek science spent most of its life under the
      shadow of the history of ideas. Despite its seemingly secondary role, however, it
      occupied a distinctive place within national historiography because it formed the
      ground upon which different perceptions of the country's European identity
      converged. In this respect, one of the main goals of this paper is to outline the
      particular ideological presumptions, which shaped the historiography of modern
      Greek science under different historical circumstances. At the end an attempt
      will be made to articulate a viewpoint more in tandem with the recent
      methodological developments in the history of science.

PMID- 19579362
TI  - Ahmed Midhat and Adnan Adivar on history of science and civilizations.
AB  - I analyze the contrasting visions of history of science in the works respectively
      of an Ottoman and a Turkish man of letters, Ahmed Midhat and Adnan Adivar, and
      claim that they perceived the link between science and cultural identity in
      different terms. Ahmed Midhat conceived of science as closely tied to its
      cultural matrix, whereas Adivar settled for a less holistic view. Both authors
      saw science as the harbinger of a new social existence, but they evaluated the
      prospects of this existence in rather divergent ways. Ahmed Midhat was concerned
      with the detrimental effects of an unquestioning appropriation of European
      scientific traditions, while Adivar had no such qualms, and celebrated the
      universalism and progressiveness of reason as revealed in history of science. I
      suggest that these differences in their outlooks presented their readers with
      civilizational choices.

PMID- 19579363
TI  - Boundaries and audiences of national histories of science: insights from the
      history of science and technology of the Netherlands.
AB  - The present paper traces the evolution of writing national-oriented histories of
      science and technology of the Netherlands. Several episodes are distinguished. A
      first wave of national histories of science and technology was written during the
      first decades of the 19th century. These histories had a wide scope, which
      included science, technology, the humanities and the arts. A second wave, which
      lasted from about 1865 to 1900, was strongly connected to the rise of the
      scientific professions. Its focus was on the sciences perse, and on the Dutch
      "Golden Age" of the 17th century. A third wave occurred during and shortly after
      the Second World War. Its focus was mainly on the "Second Golden Age" of Dutch
      science (1870-1910), and its major audience were young boys that were to be
      recruited to the sciences. The second part of the paper discusses the growing
      influence of "contextualization" in both the history of science and the history
      of technology from about 1975 onwards. As a result, local factors often received
      more attention in historical studies of science and technology than national
      influences. In 1985, Klaas van Berkel undertook a bold attempt to write a new
      synthesis of the history of Dutch science, but his approach was too strongly
      influenced by the three previous waves of national histories. From 1989 to 2003
      two projects on the national history of technology resulted in 13 volumes on
      Dutch technology between 1800 and 1970. New research was initiated, and the issue
      of "national styles" in the development of technology received ample attention.
      In his conclusions the author points to lessons to be learned from economic
      history and the history of art, and he concludes with a plea for more
      historiographical discussion in the history of science and technology.

PMID- 19579364
TI  - Writing experience: does ethnography convey a crisis of representation, or an
      ontological break with the everyday world?
AB  - This paper is premised on the "ontological break" as coined by Alfred Schutz that
      disconnects two realms: the "world of consociates" where social reality is
      directly experienced face-to-face in the vivid present, and the "world of
      contemporaries" where the other is interpreted in terms of "types." It is argued
      that this break is a suggestive vehicle for conducting a meta-exposition of major
      claims which problematize the traditional authority of ethnography. In the light
      of the break, the postmodernist attempts to attain or retain the here-and-now
      understanding of subjective meaning, or "voice" in ethnographies are but
      epistemological impossibilities. It is concluded that the postmodernist
      privileging of a "naive ethnography" which emphasizes "experiential,"
      "interpretive," "dialogical," and "polyphonic" processes is neither able to
      deliver on its promise at the methodic level, nor amendable to Schutz's
      ontological break at the theoretical level.

PMID- 19579366
TI  - New grounds for optimism.

PMID- 19579365
TI  - From community to public safety governance in policing and child protection.
AB  - The growing interoperability between policing and child protection in Canada and
      the United Kingdom suggests that we are in the midst of a governmental shift from
      community governance to public safety governance. Indeed, discourses emphasizing
      local expertise in policing and child protection have largely muted because of
      criticisms over the lack of interagency interconnectedness. Both countries have
      now developed national interagency databases for the management of persons of
      risk. This institutional integration engenders different forms of regulation. We
      conclude by arguing that this emergent ethos may be conceptualized as a nascent
      governmental rationality.

PMID- 19579367
TI  - The future of nursing: conservative style.

PMID- 19579368
TI  - See, screen and treat.
AB  - Iona McCormack was named RCN Northern Ireland Nurse of the Year last week for her
      groundbreaking work treating skin cancer.

PMID- 19579369
TI  - Matters of the heart.
AB  - Genetically inherited heart conditions can claim the lives of young, apparently
      healthy people -- but screening of family members could help save more lives.

PMID- 19579370
TI  - Spiritual calling.
AB  - The idea that patients' spiritual needs should be incorporated into nursing care
      is supported by literature and policy.

PMID- 19579371
TI  - The blame game.

PMID- 19579372
TI  - Generation gap.

PMID- 19579373
TI  - Exploring the legitimacy of intuition as a form of nursing knowledge.
AB  - This article discusses intuition as a legitimate form of knowledge rather than
      solely as an expert trait. It also describes the possibility of interdisciplinary
      research using theories and frameworks from psychology, computer science, physics
      and neuroscience to provide empirical evidence for intuitive knowledge to be
      considered a legitimate form of knowledge.

PMID- 19579374
TI  - Becoming a governor of an NHS foundation trust.
AB  - Nurses have a key role in the successful governance of NHS foundation trusts,
      either as staff governors or representatives of the public. This article explores
      the role of the governor in each of these contexts and indicates some of the
      opportunities and challenges of representing stakeholder interests.

PMID- 19579375
TI  - Emergency care of patients with gunshot wounds.
AB  - This article provides an overview of the mechanism of ballistic injuries. It also
      explores the management of patients with gunshot wounds in the emergency
      department.

PMID- 19579376
TI  - Hypothyroidism.

PMID- 19579378
TI  - Championing research.

PMID- 19579377
TI  - Reflecting on trauma.

PMID- 19579379
TI  - Generating knowledge.

PMID- 19579380
TI  - [Cattle feed: factors that influence the value of starch].

PMID- 19579381
TI  - [A localised histocytic sarcoma in the stomach of a dog].
AB  - A 6-year-old neutered female Bernese mountain dog is described with anorexia,
      weight loss and melena. Gastric neoplasia was noticed (on ultrasound) and
      pathological examination ofgastric biopsies showed a histiocytic tumor. Necropsy
      confirmed the diagnosis of a localised histiocytic sarcoma. It was remarkable
      that the large tumor didn't lead to vomiting.

PMID- 19579382
TI  - [Money collection with a strange ending].

PMID- 19579383
TI  - [Administration of radioactive holmium-166 microsphere in domestic animals with
      inoperable tumors].

PMID- 19579384
TI  - [Sighted].

PMID- 19579385
TI  - [Birds and special animals in Europe under one umbrella].

PMID- 19579386
TI  - [Free or with discount to continue education from the PEGD: the PEGD miles].

PMID- 19579387
TI  - [Vaccination campaigns in the animal specialty store].

PMID- 19579388
TI  - [Does the recession influence the turnover of a veterinary branch?].

PMID- 19579389
TI  - [The Veterinary Central Information System (VetCIS) of organization VETbase-
      Several questions from the practice].

PMID- 19579390
TI  - [Dealing with understanding and emotion--a question of trust].

PMID- 19579391
TI  - [Pilot "goat Health plan"].

PMID- 19579393
TI  - How to market public health.

PMID- 19579392
TI  - E.U. laws to enforce needlestick safety.

PMID- 19579394
TI  - How will the PCT shake-up affect nurses?

PMID- 19579395
TI  - We can improve patient care by encouraging staff to be innovative.

PMID- 19579396
TI  - New guidance shows how trusts can collect and use patient feedback to improve
      care delivery.

PMID- 19579397
TI  - Using a patient-focused approach to improve services in a nurse-led general
      practice.
AB  - A nurse-led general practice adapted its services to reflect patient feedback and
      avoid unnecessary referrals to acute care. Changes included planned extended
      services delivered collaboratively with other practices. The work by Rowley
      Healthcare to redesign services comes at a time when the NHS is keen to promote
      and spread innovation in service delivery. In April, health minister Lord Darzi
      said that strategic health authorities would receive funding to support
      innovative local projects. An Innovation EXPO where NHS staff can learn about
      innovations is being held this month in London on 18 and 19 June (NHS Institute
      for Innovation and Improvement, 2009).

PMID- 19579398
TI  - Evaluating the patient journey approach to ensure health care is centred on
      patients.
AB  - BACKGROUND: In order to become more patient focused, the City Hospitals
      Sunderland NHS Foundation Trust developed the 'patient journey' approach, which
      was a 'comprehensive practice development/service improvement' model. AIM: For an
      'outsider' (a newly qualified nurse with personal experiences as a patient) to
      implement a new patient journey in an unrelated hospital trust, to enable an
      impartial and independent evaluation of the model. METHOD: This was an action
      research study, with data collected through a variety of sources such as matrix
      sampling, project team meetings, mapping and semi-structured qualitative
      interviews. RESULTS: Participants spoke extremely highly of the care received,
      while interviews revealed more insightful and sometimes distressing information.
      A number of changes to service delivery were made as a result, including the
      introduction of a dedicated telephone line giving patients direct contact with
      the vascular nurse practitioner. DISCUSSION: The most notable attributes of the
      patient journey approach are: giving patients a 'voice'; enhancing collaborative
      multidisciplinary teamwork; shared ownership and decision-making; providing
      evidence to substantiate change; and achieving results. CONCLUSION: The City
      Hospitals Sunderland patient journey approach is an effective, patient-centred,
      collaborative service improvement model.

PMID- 19579399
TI  - Effects of bedrest 2: gastrointestinal, endocrine, renal, reproductive and
      nervous systems.
AB  - This article is the second in a three-part series discussing the effects of long
      periods of bedrest on the body. It explores what happens to the gastrointestinal,
      endocrine and renal systems when a person is confined to bed. The effects on the
      reproductive and nervous systems are also covered. Part 1 examined the effects on
      the cardiovascular, respiratory and haematological systems.

PMID- 19579400
TI  - Chemical eye injuries 1: presentation, clinical features, treatment and
      prognosis.
AB  - This is the first in a two-part unit on chemical eye injuries. It looks at
      chemical agents and their effects on the eye, and the clinical features and
      prognosis in chemical eye injuries. Extensive immediate treatment in the form of
      irrigation is essential even before a proper history and examination. This should
      be followed by aggressive early management and close long-term monitoring to
      promote ocular surface healing and provide the best possible opportunity for
      visual rehabilitation.

PMID- 19579401
TI  - On how nurses can make the health service greener.

PMID- 19579402
TI  - Public health messages need a creative approach.

PMID- 19579403
TI  - Theatre offers growing range of opportunities.

PMID- 19579404
TI  - The perception of urinary incontinence.

PMID- 19579405
TI  - Is urinary incontinence as the sixth vital sign part of your practice?

PMID- 19579406
TI  - Summary of current policy to address urinary incontinence.
AB  - Urinary incontinence is a highly prevalent problem that has a great impact on the
      quality of life of many women. Despite its prevalence, there have been few
      attempts to translate research into practice with clinical practice guidelines
      for urinary incontinence. A summary of current policy to address urinary
      incontinence and future implications for the clinician are presented.

PMID- 19579407
TI  - Incontinence patient education: strategies to enhance the teachable moment.
AB  - Patient education is one challenge many nurses face during their hectic work day.
      However, through the use of innovative teaching strategies and techniques, new
      learning experiences can be created for patients. This article will explore the
      learning process of adult patients and provides a review of various teaching
      strategies.

PMID- 19579408
TI  - Living with urinary incontinence: experiences of women from 'The last frontier'.
AB  - Urinary incontinence (UI) can be distressing for women of all ages, and in many
      cases, women are not given the opportunity to discuss urinary issues or explain
      the profound effects on quality of life. Although a few studies have examined the
      lived experience of UI in women, none have focused on Alaskan women living in the
      49th state, or "The Last Frontier". To address these gaps, this study explored
      and analyzed the experiences of 17 Alaskan women living with UI in rural and
      urban settings.

PMID- 19579409
TI  - Perceptions of embarrassment for men with and without urinary incontinence.
AB  - There is little information available about the impact incontinence has on men.
      Using photographs, men were asked to rate the perceived embarrassment of the
      wearer. Embarrassment ratings rose with the size of the visible wet area, but
      were lower from those who had experienced the problem themselves. Knowing how to
      deal with the feelings of embarrassment seems to be critical when dealing with
      incontinent males.

PMID- 19579410
TI  - Efficacy of transvaginal biofeedback and electrical stimulation in women with
      urinary urgency and frequency and associated pelvic floor muscle spasm.
AB  - Women with urinary urgency and frequency may also have pelvic floor muscle spasm.
      Transvaginal biofeedback (TVBF) and electrical stimulation (EStim) is a treatment
      modality that has been used to treat vaginismus and chronic pelvic pain. In this
      study, TVBF/EStim was evaluated in women with pelvic floor muscle spasm
      associated with urinary symptoms. Fifty-two women underwent therapy with
      TVBF/EStim and reported a mean symptom improvement of 64.5%.

PMID- 19579411
TI  - Percutaneous tibial nerve stimulation for the treatment of urinary frequency,
      urinary urgency, and urge incontinence: results from a community-based clinic.
AB  - Overactive bladder affects 16% of the adult population. This retrospective
      analysis evaluated the application of percutaneous tibial nerve stimulation
      (PTNS), a minimally invasive neuromodulation therapy, in a population of patients
      who failed to achieve adequate control of symptoms of urinary urgency, urinary
      frequency, and urinary incontinence with conservative treatments. A course of 12
      PTNS sessions was prescribed and administered in the context of an independent
      community-based, nurse practitioner-led continence practice. The results of this
      analysis indicated that patients treated with PTNS therapy experienced
      statistically significant decreases in both day and night voids, and in episodes
      of urge incontinence. This study confirmed the results of previous studies
      indicating that PTNS therapy is a safe and effective treatment that can be
      successfully incorporated in a community-based setting.

PMID- 19579412
TI  - Adding to the evidence base: perceptions of embarrassment for men with and
      without urinary incontinence.

PMID- 19579413
TI  - The cost of urinary incontinence.
AB  - It has been estimated that 13 million Americans have suffered from urinary
      incontinence (UI). Costs associated with UI include not only those pertaining to
      direct treatment, but they include costs related to the indirect psychosocial
      effects of the condition as well. This article will review both direct and
      indirect costs of UI and how urologic nurses can assist patients with UI in their
      overall plan of care.

PMID- 19579414
TI  - Culturally competent assessment and care of self-mutilation in urological
      nursing.
AB  - Use of self-mutilating behaviors as ineffective coping techniques is increasing,
      and it cuts across cultural and ethnic populations. With increasing immigration,
      the chance of facing both issues with a single patient is also increasing.
      Therefore, the need for assessment and care that is culturally sensitive is a
      necessity.

PMID- 19579415
TI  - Disseminating information for use in developing countries: a call to action.

PMID- 19579416
TI  - Getting ready for certification: antibiotics and infections.

PMID- 19579417
TI  - Antibiotic prophylaxis: what is it? Why do we care?

PMID- 19579418
TI  - [Why is managing diabetic patients so difficult?].

PMID- 19579419
TI  - [Type 1 or 2 diabetes? Or other?].
AB  - Practitioners can be faced with cases of diabetes that do not clearly correspond
      to the clinical characteristics of type 1 or type 2 diabetes. They should take
      into account forms of diabetes such as MODY or LADA, which often go unrecognised
      in spite of significant prevalence. Various tests can be conducted to measure
      insulin secretion and resistance, and to check whether the disease is auto
      immune. This makes for correct diagnosis and prescription of the appropriate
      course of treatment.

PMID- 19579420
TI  - [Which role for self-monitoring of blood glucose in type 2 diabetes?].
AB  - There is a sustained controversy in the literature about the role and utility of
      self-monitoring of blood glucose (SMBG) in type 2 diabetes. The study results in
      this field do not provide really useful clues for the integration of SMBG in the
      follow-up of the individual patient, because they are based on a misconception of
      SMBG. It is studied as if it was a medical treatment whose effect on glycemic
      control is to be isolated. However, SMBG has no such intrinsic effect. It gains
      its purpose only as an inseparable component of a comprehensive and structured
      educational strategy. To be appropriate this strategy cannot be based on the
      health care professionals' view on diabetes only. It rather has to be tailored to
      the individual patient's needs through an ongoing process of shared reflection
      with him.

PMID- 19579421
TI  - [Role and indication of GLP-1 analogues in the treatment of type 2 diabetes].
AB  - Available therapies for type 2 diabetes are not always satisfactory because they
      do not address the problems of overweight/obesity and the progressive
      deterioration of cell function. GLP-1 analogues or agonists of the GLP-1 receptor
      are a new therapeutic option which offer promises; they indeed improve glycemic
      control, decrease weight by 2-3 kg/year and may stabilize or improve cell
      function by favoring cell proliferation and inhibiting apoptosis. Their use in
      patients who are not sufficiently controlled by metformin and sulfonylurea
      compares favourably to insulin treatment.

PMID- 19579422
TI  - [Pancreas and islets of Langerhans transplantation: current status in 2009 and
      perspectives].
AB  - Type 1 diabetes currently affects 15,000 patients in Switzerland with a rising
      incidence worldwide. Pancreas or islet of Langerhans transplantation are
      alternatives to intensive insulin treatment, which decreases long-term
      complications at the cost of an increase of severe hyoglycemia. Pancreas
      transplantation, indicated mainly to diabetic patients with simultaneous kidney
      transplantation, has a high success rate, but is accompanied by high morbidity
      due to general surgery. Islet transplantation, a cell-therapy for type 1
      diabetes, is in full development. It is mainly indicated as islet transplant
      alone in patients suffering from brittle diabetes, and is associated with a very
      low risk due to minimally invasive technique, but a lower rate of long-term
      success. New potential sources of beta cell replacement are beta-cell lines, stem
      cells and xenotransplantation.

PMID- 19579423
TI  - [Metabolic dysfunction and chronic stress: a new sight at "diabesity" pandemic].
AB  - Chronic stress in Western society can activate the autonomus, neuroendocrine and
      inflammatory/immunlogic systems. Chronic exposure to stressors can indeed
      stimulate the hypothalamic-pituitary-adrenal axis and induce a disbalance between
      anabolic and catabolic hormones, responsible of an increased in visceral fat and
      of insulin resistance. These metabolic consequences can lead to pre-diabetes.
      Exposure to chronic stress results in allostatic load and its pathophysiologic
      consequences. The knowledge of this mecanisms and the cardiovascular and
      metabolic risk related, should influence our way of thinking about patient care.
      To decrease allostatic load, practitioners can rely on therapeutic relation.
      Therapeutic education is one of the skill that can be use to create therapeutic
      relation.

PMID- 19579424
TI  - [Type 2 diabetes, is it just a case of hyperglycemia? Confusion between the
      interests of science, humanity and the economy].
AB  - The recommendations for the treatment of type 2 diabetic patients are often
      centered on the glycemia. These clinical trials based on this approach show only
      a beneficial effects on the prevention of microangiopathy. The coronary artery
      disease which is the main cause of mortality among these patients, is not
      reduced. These data should be interpreted with a systemic prospect. The diabetes
      vascular complications have multifactorial causes and these clinical trials are
      motivated for the promotion of hypoglycemic agents. Fortunately, the STENO study
      offers another glance on the treatment of the diabetes, associating multirisk
      approach and patients' accompaniment. It obliges to have a critical glance on the
      research often moved by economic issues and gives to the center a humanistic
      approach based on the therapeutic relation.

PMID- 19579425
TI  - [The development of guidelines and their lower levels of evidence].

PMID- 19579426
TI  - [Circulate...there is nothing to see!].

PMID- 19579427
TI  - [The numbers of the World Health Organization are no longer credible].

PMID- 19579428
TI  - [Red Bull energy drink, a year later: nothing to report].

PMID- 19579429
TI  - [Abstaining from alcohol for 24 hours - testing for alcoholism].

PMID- 19579430
TI  - [Personal losses, menopause, and estrogen treatment].

PMID- 19579431
TI  - [A mnemonic for patient relations - 3A2B2CDE].

PMID- 19579432
TI  - [Patient safety--USA is abandoning the way suggested in Sweden].

PMID- 19579433
TI  - [JUPITER no support of changed guidelines for cardiovascular prevention. Moderate
      absolute risk reduction and uncertain long term effects].

PMID- 19579434
TI  - [Plasmodium knowlesi--the fifth malaria. Potentially lethal infection which can
      also affect tourists].

PMID- 19579435
TI  - [JUPITER can yield paradigmatic shift in the prevention of cardiovascular
      disease. Focus on inflammation as a risk factor].

PMID- 19579436
TI  - [New therapeutic possibilities in chronic ITP in adults].

PMID- 19579437
TI  - [Increased level of knowledge within suicide prevention wanted. A literature
      review of evidence-based studies].

PMID- 19579438
TI  - [Health clinics work with sexually transmitted infections has shortages. A
      national survey shows great variations between different clinics].

PMID- 19579439
TI  - [The zero vision for suicide breaks the taboo].

PMID- 19579440
TI  - [Quality--a matter of professional judgment].

PMID- 19579441
TI  - [About quality registries: are we afraid the results will not be the ones we
      wanted?].

PMID- 19579442
TI  - [This is how we want the new reimbursement system for private practitioners].

PMID- 19579443
TI  - [Doctor Guillotin didn't believe in the life of the head after the axe].

PMID- 19579445
TI  - Small hospitals at a crossroads.

PMID- 19579446
TI  - Lessons from the credit crisis.

PMID- 19579444
TI  - Directors and officers insurance.

PMID- 19579447
TI  - Mass appeal?

PMID- 19579448
TI  - A nurse's voice at the table.

PMID- 19579449
TI  - Why boards must match CEO competencies with strategic priorities.

PMID- 19579450
TI  - Safety in a recession?

PMID- 19579451
TI  - Making more effective executive selections.

PMID- 19579452
TI  - Lessons learned from Las Vegas.

PMID- 19579453
TI  - It's a great time to try incentives.

PMID- 19579454
TI  - Buying an AED is just the first step.

PMID- 19579455
TI  - Grasping hand safey.

PMID- 19579456
TI  - The personal touch.

PMID- 19579457
TI  - Vision testing for the safety professional, Part 2.

PMID- 19579458
TI  - Can't pee, eh? Sometimes, the emergency is pretty clear.

PMID- 19579459
TI  - Drinking herself to death. But it's not just a high BAC threatening this young
      college student.

PMID- 19579460
TI  - EMS & FedEx ... the similarities should be more striking than the differences.

PMID- 19579461
TI  - A tactical approach to scene safety. Applying safety awareness to every call can
      improve your odds against violent patients.

PMID- 19579462
TI  - Stemi care: evolution of a benchmark.

PMID- 19579464
TI  - SCA: 25 steps to ending survival envy.

PMID- 19579463
TI  - Cue the cath lab. A Maine service gives medics the power to activate, with good
      results.

PMID- 19579465
TI  - Debate: direct cath lab activation by paramedics.

PMID- 19579466
TI  - Stable or unstable? Assessment and management of ventricular tachycardia with
      pulses.
AB  - Ventricular tachycardia represents ectopic cells within the ventricles
      stimulating the heart to contract. Many conditions cause ventricular tachycardia,
      including myocardial muscle deterioration and drug stimulation. The symptom most
      suggestive of unstable ventricular tachycardia is a change in mental status or
      loss of consciousness. Stable ventricular tachycardia is managed with
      antiarrhythmic medications, while unstable ventricular tachycardia requires
      immediate cardioversion. After converting ventricular tachycardia to a sinus
      rhythm, administer an antiarrhythmic infusion.

PMID- 19579467
TI  - Just a headache? What EMS providers need to know about the signs and symptoms of
      headaches.
AB  - There are many more causes or conditions that may present as a severe headache,
      and it is sometimes difficult to get a complete understanding of what the patient
      is experiencing. Keeping in mind our caregivers' mantra to "do no harm," and
      keeping all senses in tune to your patient's presentation, you'll go a long way
      toward making your patient feel better and instilling them with confidence that
      you care.

PMID- 19579468
TI  - Professional development. Part 5: Performance evaluation.

PMID- 19579469
TI  - "Just a little pinch ...." Some memorable gaffes from those early, awkward
      patient interviews.

PMID- 19579471
TI  - Conducting the fire watch of standard LS.01.02.01.

PMID- 19579470
TI  - Study ties Joint Commission accreditation to improved emergency preparedness.

PMID- 19579472
TI  - Revision: hospital definition of physician.

PMID- 19579473
TI  - Update: additional scoring changes for all 2009 accreditation manuals.

PMID- 19579474
TI  - Q&A: understanding hospital deemed status accreditation reports.

PMID- 19579475
TI  - [The mandarins and the directors].

PMID- 19579476
TI  - [Increase of the fees of the National Order of Nurses set at 75 euros].

PMID- 19579477
TI  - ["The Appeal of 39", a movement in psychiatry].

PMID- 19579478
TI  - [An ambulance service specialised in psychiatry (interview by Patrick Touzet)].

PMID- 19579479
TI  - [Elaboration of a nursing ethic].

PMID- 19579480
TI  - [The complex world of drug dependence, of intoxication and addiction].

PMID- 19579481
TI  - [New concepts and current practices in addiction treatment].

PMID- 19579482
TI  - [Addiction to video games or how to hold the world in one's closed fist].

PMID- 19579483
TI  - [Pathological gambling, an addiction without drugs].

PMID- 19579484
TI  - [The new drug addiction behavior of the young].

PMID- 19579485
TI  - [Ecstasy, new psychotropic drugs].

PMID- 19579486
TI  - [The nursing team of an addiction service].

PMID- 19579487
TI  - [Being there, a nursing function with many dimensions in a "place in life"].

PMID- 19579488
TI  - [Request for access to the medical record].

PMID- 19579489
TI  - [Medico-legal study on crashes of fighter planes of the National People's Army].
AB  - In the years 1974 to 1990, 39 pilots died in 34 crashes of fighter planes of the
      National People's Army; 32 victims were examined forensically. For the present
      study all autopsy protocols and examination reports available in the German
      Federal Military Archives in Freiburg could be evaluated. Both officer cadets and
      experienced pilots of high military ranks were among the victims. The majority of
      the crashes (24 out of 34) was caused by human failure. Health problems or the
      use of alcohol and medications did not play a role in the aircraft accidents. All
      killed pilots were identified. The injury patterns after fatal ejection are
      different from the patterns seen after impact with a plane. Such patterns of
      findings are meaningful in the reconstruction of unknown sequences of events
      leading to the accidents and for the assessment of the pilots' capacity to act at
      the moment of the incident

PMID- 19579490
TI  - [Results of an investigation of enamel fragments from Benvenuto Cellini's
      "Saliera" using energy-dispersive X-ray microanalysis (EDX)].
AB  - A blackmail letter was submitted in the context of the theft of Cellini's salt
      cellar (Saliera) from the Museum of Fine Arts in Vienna. Dark blue enamel
      fragments were included in this letter as a proof of authenticity. The comparison
      of this material with enamel believed to originate from the original artwork,
      using microspectrography and energy-dispersive X-ray microanalysis (EDX) in the
      scanning electron microscope showed similar elemental composition. Accordingly,
      the further investigations could concentrate on this blackmail attempt in spite
      of numerous other confession letters received.

PMID- 19579491
TI  - [Retrospective analysis of changes concerning presumable homicidal poisoning in
      the region of the Bonn University Department of Legal Medicine over the last 6
      decades].
AB  - 10,739 autopsy protocols from 1946-2005 were retrospectively analysed as to
      whether they included cases of homicidal poisoning with special attention being
      paid to the substances used, characteristic features of the perpetrators and the
      circumstances of their detection. Amongst the 882 homicides, there were 15
      confirmed cases of homicidal poisoning (1.7%). The incidence of this method of
      killing has clearly decreased over the years, while the number of homicides among
      the autopsies performed remained almost constant. There was a change concerning
      the substances used with heavy metals and E 605 (parathion) in the 40's and 50's
      being replaced by highly volatile substances and medicinal drugs, which are
      difficult to detect by analytical methods. In most cases, the perpetrator and the
      victim had close relations with males and females being equally represented in
      the number of perpetrators. 27% of the victims had to be exhumed and in 13% the
      homicide was detected only after essential hints had been given by the offenders
      themselves or their surroundings. This points to a larger number of undetected
      cases.

PMID- 19579492
TI  - [Reconstruction of a fire homicide after pouring denatured alcohol on the
      victim].
AB  - A 48-year-old man died from extensive burns suffered especially on the upper part
      of the body during a dispute with his ex-wife, who had poured spirit or a spirit
      water mixture over him. For initially unknown reasons, the man's clothing caught
      fire. Whereas the public prosecutor assumed that the woman had intentionally
      poured a larger amount of spirit over her ex-husband before setting fire to him,
      the defendant first claimed to have poured the rest of a water-spirit mixture
      left over from cleaning the windows over the man and that his clothing caught
      fire on lighting a cigarette. To clarify the course of events, fire tests with
      spirit in various dilutions were conducted, which showed that even with undiluted
      spirit a direct contact with the flame of at least 1 second is necessary to start
      a fire. There is no deflagration, if spirit is used as a fire accelerant. In the
      trial, the defendant made a confession and admitted to have poured a mixture of
      75% spirit and 25% water over her ex-husband and set fire to his right sleeve
      with the intention to kill him.

PMID- 19579493
TI  - [Safely enjoying the sun].

PMID- 19579495
TI  - ["Only one who burns can burn out". Caregivers and burnout syndrome in health
      care careers].

PMID- 19579494
TI  - [Somatoform dissociations in children and adolescents].

PMID- 19579496
TI  - [References for healthy treats for returning to school].

PMID- 19579497
TI  - [Promoting resilience--(how) can it be done?].

PMID- 19579498
TI  - [Intensive care at the end of life].

PMID- 19579499
TI  - [The first autonomous midwives receive the birthing quality seal].

PMID- 19579500
TI  - [Interview with Horst Stengritt (interview by Angelika Staub)].

PMID- 19579501
TI  - [WldO study in a current hospital report shows: by increasing minimum numbers of
      premature and newborn infants with very low birth weight treated mortality can be
      avoided].

PMID- 19579502
TI  - [Home nursing of severely ill children in Lower Saxony is improved].

PMID- 19579503
TI  - Adrift in PolicyLand.

PMID- 19579504
TI  - Advanced education.

PMID- 19579505
TI  - The HCI 100.

PMID- 19579506
TI  - M&A's small steps.

PMID- 19579507
TI  - Athenahealth. Service first.

PMID- 19579508
TI  - Siemens. Ready for takeoff.

PMID- 19579509
TI  - Nuance. The spoken word.

PMID- 19579510
TI  - One-on one with NYCHHC president and CEO Alan Aviles. Interview by Daphne
      Lawrence.

PMID- 19579511
TI  - One-on-one with MemorialCare Medical Centers CIO Scott Joslyn. Interview by
      Daphne Lawrence.

PMID- 19579512
TI  - One-on-one with Newark Beth Israel VP & CIO Tomas Gregario. Interview by Kate
      Huvane Gamble.

PMID- 19579513
TI  - One-on-one with Lowell General Hospital CIO John Goodrow. Interview by Kate
      Huvane Gamble.

PMID- 19579515
TI  - The physician factor.

PMID- 19579514
TI  - One-on-one with Christus Health SVP & CIO George Conklin. Interview by Mark
      Hagland.

PMID- 19579516
TI  - Going with the flow: lessons from disruptive change.

PMID- 19579517
TI  - Are you building bench strength?

PMID- 19579518
TI  - Providing care as a team.

PMID- 19579519
TI  - Reducing urinary incontinence.

PMID- 19579520
TI  - Getting the most out of advancing excellence.

PMID- 19579521
TI  - 2009. Weathering the storm.

PMID- 19579522
TI  - 2009. Assisted living feels pinch.

PMID- 19579523
TI  - Experimental formation of periodontal structure around titanium implants
      utilizing bone marrow mesenchymal stem cells: a pilot study.
AB  - Tissue engineering in the head and neck area, presents numerous advantages. One
      of the most remarkable advantages is that regeneration of only a small amount of
      tissue can be highly beneficial to the patient, particularly in the field of
      periodontal tissue regeneration. For decades, successful osseointegration has
      provided thousands of restorations that maintain normal function. With the
      increasing need to utilize dental implants for growing patients and enhance their
      function to simulate normal tooth physiology and proprioception, there appears to
      be an urgent need for t concept of periodontal tissue regeneration around dental
      implants. In the present work, 5 goats wer used for immediate implant placement
      post canine teeth extraction. Each goat received 2 implan fixtures; the control
      side received a porous hollow root-form poly (DL-Lactide-co-Glycolide) scaf
      around the titanium fixture, and the experimental side received the same scaffold
      but seeded with autogenous bone marrow-derived mesenchymal stem cells. One animal
      was killed 10 days postoperatively, and the others were killed after 1 month. The
      results showed that on th experimental side, periodontal-like tissue with newly
      formed bone was demonstrated both at 1 days and after 1 month, while the control
      specimens showed early signs of connective tissue regeneration around the
      titanium fixture at 10 days, but was not shown in the 1 month specimens. I can be
      concluded that undifferentiated mesenchymal stem cells were capable of
      differentiating t provide the 3 critical tissues required for periodontal tissue
      regeneration: cementum, bone, a periodontal ligament. This work may provide a new
      approach for periodontal tissue regeneration.

PMID- 19579524
TI  - Effect of implant design on initial stability of tapered implants.
AB  - Implant design is one of the parameters for achieving successful primary
      stability. This study aims to examine the effect of a self-tapping blades implant
      design on initial stability in tapered implants. Polyurethane blocks of different
      densities were used to simulate different bone densities. The two different
      implant designs included one with self-tapping blades and one without self
      tapping blades. Implants were placed at 3 different depths: apical third, middle
      third, and fully inserted at 3 different densities of polyurethane blocks. A
      resonance frequency (RF) analyzer was then used to measure stability of the
      implants. Repeated-measures analysis of variance was used to examine the effect
      of implant design, insertion depth, and block density on RF. Analysis of
      covariance was used to examine the strength of association between RF and the
      aforementioned factors. In both medium-density (P = .017) and high-density (P =
      .002) blocks, fully inserted non-self-tapping implants showed higher initial
      stability than self-tapping implants. No differences were noted between the 2
      implant designs that were not fully inserted. The highest strength of association
      was with insertion depth (standardized beta [std beta] = -0.60, P = .0001),
      followed by block density (std beta = -0.15, P = .0002). Implant design showed a
      weak association (std beta = -0.07, P = .09). In conclusion, fully inserted
      implants without self-tapping blades have higher initial stability than implants
      with self-tapping blades. However, the association strength between implant
      design and initial stability is less relevant than other factors, such as
      insertion depth and block density. Thus, if bone quality and quantity are
      optimal, they may compensate for design inadequacy.

PMID- 19579525
TI  - Immediate placement and temporization of implants: three- to five-year
      retrospective results.
AB  - The immediate placement of dental implants in esthetic areas is a primary
      challenge for modern implantology. The underlying treatment goal is to preserve
      the natural periodontal architecture; in recent years, however, a concurrent goal
      has been to reduce the period between implant placement in the fresh extraction
      socket and delivery of the definitive restoration, but adequate long-term data
      are still lacking on the efficacy of this technique. A 3- to 5-year retrospective
      analysis of 282 dental implants immediately placed into extraction sockets, and
      temporized with nonoccluding provisional prostheses has been undertaken. All
      recorded outcomes and complications, as well as a proposed protocol for
      management of immediate function, are discussed.

PMID- 19579526
TI  - Implant rehabilitation for a patient with Hallerman-Streiff syndrome: a case
      report.
AB  - Hallermann-Streiff syndrome is a rare genetic disorder characterized by
      craniofacial malformations, sparse hair, eye abnormalities, dental defects,
      degenerative skin changes, and short stature. The syndrome has many implications
      for dental treatment. Patients typically present with multiple missing and poorly
      formed teeth. The purpose of this case report is to discuss the overall
      management of a patient with Hallermann-Streiff syndrome by oral maxillofacial
      surgery, orthodontic treatment, and prosthodontic reconstruction.

PMID- 19579527
TI  - Air pollution effects on ventricular repolarization.
AB  - We conducted a retrospective study of a set of previously published
      electrocardiographic data to investigate the possible direct association between
      levels of particulate air pollution and changes in ventricular repolarization --
      the cardiac electrophysiologic process that manifests itself as the T wave* of
      the electrocardiogram (ECG) and that is definitively linked to and responsible
      for increased arrhythmogenesis. The published findings from this data set
      demonstrated a clear cardiac effect, namely, a reduction in heart rate
      variability (HRV) parameter values with increased levels of particulate air
      pollution (Pope et al. 2004), suggesting possible arrhythmogenic effects. Given
      this positive finding and the well-established sensitivity of cardiac
      repolarization to physiologic, pharmacologic, and neurologic interventions, and
      in light of emerging novel tools for assessing repolarization, we hypothesized
      that high levels of particulate air pollution would alter repolarization
      independent of changes in heart rate and, consequently, would increase
      arrhythmogenic risk. The likely mechanism of any deleterious effects on
      repolarization would be alteration of sodium, calcium, and potassium channels.
      The channel's structure, function, and kinetics are responsible for generating
      the cellular action potentials, which, when summed over the entire heart, result
      in the waves recorded by the ECG. A positive finding would provide evidence that
      increased levels of air pollution may be directly linked to increases in
      arrhythmogenic risk and, potentially, sudden cardiac death. The study population
      consisted of 88 nonsmoking, elderly subjects in whom multiple, continuous, 24
      hour, 2-channel ECG recordings were collected, along with blood samples to
      evaluate inflammatory mechanisms (not pursued in the current study). The
      concentration of fine particulate matter (PM2.5, particulate matter with an
      aerodynamic diameter < or = 2.5 microm) in daily samples was measured or
      estimated and used to trigger recording sessions for days considered to have
      "low" or "high" PM2.5 concentrations. Each subject participated in one to five
      recordings over the study period, and all subjects lived within the greater Salt
      Lake Valley in Utah. We reanalyzed these recordings using custom software that
      incorporated a magnitude function of the ECG -- the root mean square of all
      recorded leads (RMS ECG) -- to determine the following for each beat in the 24
      hour recording: cycle length (RR); RR dispersion; the interval between the RMS R-
      and T-wave peaks (RT), a robust estimate of mean duration of ventricular action
      potential; the width of the RMS T wave (TW), a robust estimate of the range of
      repolarization times that relates to repolarization dispersion and
      arrhythmogenesis; the RMS QT interval (QT) measured from the QRS onset to T-wave
      offset of the RMS ECG; and the regression slopes of RT versus RR, QT versus RR,
      and TW versus RR, which provide estimates of so-called repolarization
      restitution, or rate dependency of repolarization, which also is associated with
      arrhythmogenesis. The study findings did not support the original hypothesis and
      demonstrated a lack of sensitivity of repolarization to changes in PM2.5
      concentrations. None of the repolarization variables showed a statistically
      significant change between days of low and high PM2.5 concentrations, although we
      observed statistically significant differences for some variables using fixed
      effects modeling. However, we did find a significant decrease in the standard
      deviation of cycle length, in concert with findings in the original study that
      showed a decrease in HRV parameter values. There was a slight but statistically
      insignificant increase in the width of the TW between recordings from days of low
      and days of high PM2.5, suggesting that, in a setting of prolonged exposure to
      high levels of PM, the original hypothesis might be supported. We conclude that
      in this study the short-term (day-today) differences in air pollution,
      specifically PM2.5 concentration, did not affect ventricular repolarization. A
      likely explanation for the negative result is that the day-today variability of
      repolarization (arising from autonomic influences, activity, and heart rate) far
      outweighs the changes that might be induced by air pollution, if any. In
      addition, the study may have been underpowered. The findings do not refute the
      possibility of the deleterious repolarization effects of PM, particularly over
      prolonged periods of exposure, but suggest the need for exposure studies that
      provide better controls. In light of recent studies, it is also likely that in an
      at-risk population -- for example, patients compromised with heart disease --
      repolarization changes may be more apparent.

PMID- 19579528
TI  - Earnings sharing in Social Security: projected impacts of alternative proposals
      using the MINT model.
AB  - Changes in American family and work patterns over the past decades have prompted
      various policy proposals for changing the structure of Social Security benefits.
      In this article, we use the Social Security Administration's Modeling Income in
      the Near Term (MINT) microsimulation model to project how Social Security benefit
      amounts would change in response to incorporating earnings sharing into benefit
      calculations for the population aged 62 or older in 2030 under three hypothetical
      policy scenarios. The earnings sharing scenarios modeled in the article would
      reduce benefits for the majority of individuals, although there are important
      differences among married, divorced, and widowed individuals. Some groups of men
      and women would experience increases in Social Security benefits, while some
      would receive reduced benefits in comparison to current law, particularly widowed
      individuals. Allowing widows to inherit the earnings records of their deceased
      husbands would improve their outcomes.

PMID- 19579529
TI  - Examining Social Security benefits as a retirement resource for near-retirees, by
      race and ethnicity, nativity, and disability status.
AB  - This article analyzes Social Security benefits as a retirement resource for
      selected subgroups of recent cohorts of near-retirees. The analysis therein
      examines the distribution of benefits among subgroups by (1) race and ethnicity,
      (2) nativity, and (3) disability status. We use improved data (actual earnings
      histories) to produce more accurate measures of benefits. We look at how the
      average values of several benefit measures, such as Social Security wealth and
      earnings replacement rates, differ among the selected subgroups and discuss
      reasons for these differences. This study finds that substantial differences in
      earnings levels and/or mortality levels among these subgroups interact with
      Social Security program provisions to produce sizable differences in the values
      of our benefit measures.

PMID- 19579530
TI  - Elderly poverty and Supplemental Security Income.
AB  - In the United States, poverty is generally assessed on the basis of income, as
      reported in the Current Population Survey's (CPS's) Annual Social and Economic
      Supplement (ASEC), using an official poverty standard established in the 1960s.
      The prevalence of receipt of means-tested transfers is underreported in the CPS,
      with uncertain consequences for the measurement of poverty rates by both the
      official standard and by using alternative "relative" measures linked to the
      contemporaneous income distribution. The article reports results estimating the
      prevalence of poverty in 2002. We complete this effort by using a version of the
      2003 CPS/ASEC for which a substantial majority (76 percent) of respondents have
      individual records matching administrative data from the Social Security
      Administration on earnings and receipt of income from the Old-Age, Survivors, and
      Disability Insurance and Supplemental Security Income (SSI) programs. Adjustment
      of the CPS income data with administrative data substantially improves coverage
      of SSI receipt. The consequence for general poverty is sensitive to the merge
      procedures employed, but under both sets of merge procedures considered, the
      estimated poverty rate among all elderly persons and among elderly SSI recipients
      is substantially less than rates estimated using the unadjusted CPS. The effect
      of the administrative adjustment is less significant for perception of relative
      poverty than for absolute poverty. We emphasize the effect of these adjustments
      on perception of poverty among the elderly in general and elderly SSI recipients
      in particular.

PMID- 19579531
TI  - Uses of administrative data at the Social Security Administration.
AB  - The Social Security Administration (SSA) collects a wealth of data in its role as
      administrator of two large national entitlement programs. Linking SSA's
      administrative data with survey data yields a broader set of demographic and
      socioeconomic information and also improves the quality of the survey data. The
      agency uses these data to produce analyses and research on policy initiatives for
      its programs and on the earnings of the working and beneficiary populations. SSA
      studies how these programs and potential changes to them affect individuals, the
      economy, and program solvency, and develops models to project demographic and
      economic characteristics of the current working population into the future. The
      agency also produces public-use microdata files that are available to outside
      researchers, as well as a variety of research and statistical publications to
      inform policymakers and the public.

PMID- 19579532
TI  - Defining the public, defining sociology: hybrid science-public relations and
      boundary-work in early American sociology.
AB  - In this paper, I examine how scientific disciplines define their boundaries by
      defining the publics with whom they engage. The case study is an episode in the
      development of early American sociology. In response to the dual challenge of
      credibility set up by the conflict between religious Baconian science and secular
      positivist science, key actors engaged in specific strategies of boundary-work to
      create their desired "sociological public"--a hybrid form of science-public
      relations that appealed to hostile university scientists while excluding a
      supportive religious audience from participation in the production of scientific
      knowledge. Using this case, I offer two specific insights. First I illustrate
      how, in the pursuit of scientific credibility, actors engage in boundary-work to
      differentiate audiences, not just practitioners. Such defining of publics is
      constitutive of scientific disciplines in their formative stage. Second, I
      demonstrate how audience boundaries can be redefined through the capture of
      existing boundary objects. Specifically, the removal of informational content in
      key boundary objects creates durable boundaries that are difficult to overcome.

PMID- 19579533
TI  - Manufacturing doubt: journalists' roles and the construction of ignorance in a
      scientific controversy.
AB  - In recent decades, corporate and special interests have developed a wide
      repertoire of methods to manufacture doubt about science that threatens their
      interests. In the case presented here, a trade association issued a rich
      assortment of rhetorical claims intended to sow public confusion about university
      studies that threatened to undermine its industry's activities. Journalists' use
      of these claims appeared to vary largely as a function of their perceptions of
      their journalistic roles and of their audiences, though their knowledge of
      science also appeared to play a role. Our findings offer insight into how and why
      reporters respond to rhetorical claims about scientific ignorance and uncertainty
      that actors use to discredit threatening science. In so doing, they contribute to
      growing scholarship on journalists' contributions to the social construction of
      ignorance in scientific controversies.

PMID- 19579534
TI  - Just around the corner: rhetorics of progress and promise in genetic research.
AB  - The emerging "diabetes epidemic" threatens to affect 366 million people worldwide
      by 2030. In the UK, almost 2 million people (about 3.9 percent of the population)
      are currently diagnosed with diabetes and it is estimated that a further 1
      million people have the disease but do not realize it. The prevalence of
      diabetes, its complications and their effects on the lives of those living with
      diabetes mean that diabetes research has the potential to bring significant
      benefits. In this paper, we are concerned with the research involving human
      embryonic stem (HES) cells that sees diabetes as a potential therapeutic
      location. Drawing on the idea of the "certainty trough" we examine how the hopes
      and uncertainties associated with this complex research agenda are understood. We
      show that those at the research front and those most opposed to the research
      agenda appear to be the most aware of the uncertainties that need to be resolved.
      In contrast, funders, typically one-step removed from the research work, see the
      promise of the research as more real and more likely to be achieved.
      Significantly, these optimistic funders are supported in their beliefs by the
      research scientists as constitutive claims are reproduced within the contingent
      forum. The effect is a collaborative project in which the promise of a technical
      solution "just around the corner" is sustained whilst concerns about the future
      difficulties are marginalized.

PMID- 19579535
TI  - "Public" perceptions of gamete donation: a research review.
AB  - This paper reviews the literature on "public" perceptions of the practice of
      gamete (egg and sperm) donation in the treatment of infertility. Despite regular
      "consultation" exercises in the UK on the manner in which infertility treatments
      should be regulated, there is little sense of how a range of public groups
      respond to developments in this area. The key themes from thirty-three articles,
      chapters and reports are discussed. The review reveals the limited nature of our
      current knowledge of public understandings of and attitudes towards gamete
      donation as a form of infertility treatment which has been readily available and
      widely practiced for many years. The review is critical of the methodological and
      epistemological basis of much of the work in this area and argues that there is a
      strong case for social scientific research to attempt to capture the perceptions
      of a wider range of people who are rarely included in formal public consultations
      and often similarly excluded from research studies.

PMID- 19579536
TI  - Staging scientific controversies: a gallery test on science museums'
      interactivity.
AB  - The "transfer" model in science communication has been addressed critically from
      different perspectives, while the advantages of the interactive model have been
      continuously praised. Yet, little is done to account for the specific role of the
      interactive model in communicating "unfinished science." The traditional
      interactive methods in museums are not sufficient to keep pace with rapid
      scientific developments. Interactive exchanges between laypeople and experts are
      thought mainly through the lens of a dialogue that is facilitated and framed by
      the traditional "conference room" architecture. Drawing on the results of a small
      scale experiment in a gallery space, we argue for the need for a new
      "architecture of interaction" in museum settings based on art installation and
      simulation techniques, which will enhance the communication potentials of science
      museums and will provide conditions for a fruitful even-handed exchange of expert
      and lay knowledge.

PMID- 19579537
TI  - Consultations of stakeholders on the roles of research in relation to genetically
      modified plants in France.
AB  - This article reports the first consultations on the roles of research in relation
      to genetically modified plants in France. We present a new attempt at
      facilitating discussion towards acceptable decisions and their results. This
      method consists of three steps: individual in-depth interviews of 77 French
      stakeholders, analysis of the interviews to identify elements that could help a
      constructive debate among participants, and two round-table discussions to
      present this analysis to stakeholders and foster discussions among them. The
      interviews exhibit a diversity of perceptions that are vaster than the pro or
      against points of view within the media. The problems raised during interviews
      deal with how discussions on genetically modified organisms (GMOs) are being
      done, how risks are taken into account, how the information is diffused, and how
      there is a minimal level of attention paid to social needs in GMOs' production. A
      series of problems more specific to the subject of the study discuss the
      weaknesses of the public research system. On the basis of these problems, 21
      elements were identified that the stakeholders would like to see improved. One
      request seemed to be important for all types of stakeholders: "Raising the
      objectivity of the debate on GMOs." Our facilitation exercise led to a set of
      innovative concrete proposals for the design of an effective national debate.

PMID- 19579538
TI  - Consumer attitudes and the governance of food safety.
AB  - This paper reports the analysis of a recent study of public perception of food
      safety governance in Spain, using genetically modified (GM) foods as an
      indicator. The data make clear that Spanish food consumers are aware of their
      rights and role in the marketplace. They are critical of current regulatory
      decision making, which they perceive to be unduly influenced by certain social
      actors, such as industry. In contrast, consumers demand decisions to be based
      primarily on scientific opinion, as well as consumer preferences. They want
      authorities to facilitate informed purchasing decisions, and favor labeling of GM
      foods mostly on the grounds of their right to know. However, consumers' actual
      level of knowledge with respect to food technology and food safety remains low.
      There are several ambivalences as to the real impact of these attitudes on actual
      consumer behavior (specifically when it comes to organizing themselves or
      searching out background information).

PMID- 19579539
TI  - The prostate cancer screening debate: public reaction to medical controversy in
      the media.
AB  - This study explored older men's and their partners' reactions to a television
      news program on the medical debate surrounding the use of the prostate-specific
      antigen (PSA) test for prostate cancer screening. Six focus groups, split by
      gender and socio-economic status (SES), were conducted with men aged 50 years or
      older (n = 28) and female partners of such men (n = 13). A self-completion
      questionnaire was also used to yield quantitative indices. In general, viewers
      appeared to appreciate from the debate that there was controversy surrounding
      prostate cancer screening, and they recognized that PSA testing is more
      applicable to certain subgroups of men. Although there were differences by SES
      and gender, the results suggest that exposing health consumers to medical
      uncertainty and "expert" conflict can help raise awareness of the issue and
      complexities involved. However, there was evidence to suggest that health
      consumers may be better able to negotiate conflicting medical information if the
      different sides of the argument are plainly noted and a clear distinction is made
      between opinion and evidence. This study has broader relevance to the management
      of media coverage of medical controversies by public health organizations.

PMID- 19579540
TI  - [ The hospitalization of Jews in mental hospitals under Vichy in the department
      of the Seine].
AB  - The author presents the state of his research about a question not very studied
      till now in a French department whose specificities have to be considered. The
      studying of some fifty medical records and some unpublished documents allows to
      point out how people persecuted by racial laws have been set in psychiatric
      hospitals and protected. As for their goods it seems that the system intending to
      protect psychiatric in-patients during their stay at the hospital has been turned
      away and used to despoil the patents "claimed or alleged Jews".

PMID- 19579541
TI  - [1791: a decisive moment in endocrine surgery].
AB  - On the 20th of May 1791 a women aged 24 presented herself at the "Hotel-Dieu" in
      Paris. She sufferd of a frontal cervical tumor. This giante tumor obliged Pierre
      Joseph Desault, chief surgeon, to accept the removal of the tumor. At the dawn of
      the XIX century this operation based on new precepts stand as a fundamental
      rupture in the approach of treatment of goiter.

PMID- 19579542
TI  - [About Philippe Ricord].
AB  - As chief of a department of the Hospital of the Venereal Patients from 1832 to
      1861, Ricord was a practitioner in vogue well-known in the political and artistic
      people of Paris as he had be taken medical advice by Gaetano Donizetti in 1845
      and Jules de Goncourt in 1869. His fame was brilliant in proportion of his
      financial success. His personal tools--ivory speculum and gilded tools--are in
      his own image. The author shows a surgery tool-box carved with Ricord's name and
      probably manufactured by Charriere about 1865.

PMID- 19579543
TI  - [Homage to Professor Andre Cornet (March 31, 1911-July 20, 2007), former
      President of the French Society of the History of Medicine].
AB  - As he was the general secretary of the Society for eleven years, Doctor Alain
      Segal, gastroenterologist, paid tribute to Professor Andre Cornet for his
      determining action during the six years of his chairmanship of the Society. The
      length of this period was unusual according to the statutes but it allowed him
      thanks to his watchful and well-accepted authority to save our Society from a
      threatening disaster. The author evoked professor Cornet's contribution to the
      history of our art in Histoire des Sciences medicales with the help of his wife,
      doctor Anna Cornet.

PMID- 19579545
TI  - [History of imaging: cases under study].
AB  - Techniques of body scanning and imaging each give a partial picture of the cases
      under study, with technical limitations connected to translation parameters,
      scanning frequency, etc. 3D imaging can analyze foetuses, "dedicated" imaging can
      detect focus of inflammation(?). Will today's techniques such as scintiscanning
      or scanning become obsolete within the coming decade? The protection of medical
      personnel and patients must be improved.

PMID- 19579544
TI  - [Of scanning and imaging: I remember].
AB  - Modern imaging and body scanning techniques appeared some 40 years. They have
      revolutionized the practice of diagnostic medicine. Some pioneers in this field
      are here to witness their earlier inventions being made obsolete by the rapid
      development of computer and electronic techniques. Since the first bronchial
      endoscopies performed in 1956, applications of imaging techniques have become
      commonplace. However, the virtual world has not yielded yet to the human capacity
      to perceive and integrate. This is a challenge to physicians who are more bound
      today to the dictates of engineering than to clinical practice.

PMID- 19579546
TI  - [Small conclusions of the moment].
AB  - The author provides a little momentary conclusion about the medical scanning,
      term coined since 1989. As a matter of fact he could directly live some great
      times through the studious friendship of his father with professors Jean-marie
      Dubois de Montreynaud and Charles Debray. The three of them were great
      researchers about the means offered by this technique. The author tries to make
      share the thoughts he has compared with the philosopher of the imagery, Francois
      Dagognet, about the medical videology. So in front of such a swiftly evolution of
      several techniques of medical imagery it is not amazing that we are finally led
      to a very momentary conclusion.

PMID- 19579547
TI  - [The thyroid one and goiter through the ages].
AB  - The written works and the works of art testify the goitres existed over thousands
      of years. However for a long time they were confused with scrofula and several
      cervical tumours. In fact the thyroid gland was only discovered and described at
      Renaissance and its role was known at the end of the XIXth century. The treatment
      of goitre remained vague even though as soon as the ancient times seaweed and
      sponge ashes were prescribed, that was premonitory therapeutic approach. As for
      the surgical treatment, it appeared only one century ago and it is noticeable
      that the first surgeons who operated goitres played a significant role in the
      understanding of the thyroid physiology.

PMID- 19579548
TI  - [The Boucicaut hospital: a century of history].
AB  - Hospital Boucicaut opened on November 22, 1897. This hospital is dominated by Mrs
      Boucicaut. The main activity at the beginning was tuberculosis. Many doctors
      became famous: Maurice Letulle for histopathology, Jean Lenegre for cardiology;
      Leroux Robert for laryngeal operations; Raymond Vilain for SOS Mains; Jacques
      Lissac for reanimation. The hospital was old and had to be transferred into the
      new European Hospital Georges Pompidou in 2000.

PMID- 19579549
TI  - [The doctor as seen by advertisements of drug companies of the 20th century].
AB  - Pharmaceutical advertising during the XXth century was related to many subjects,
      the objective being to amuse physicians. One of the subject was the physician
      himself and its image throughout history. What can be found is the idea that the
      physician inherits a long tradition, but he is also able to laugh at himself
      doing his art.

PMID- 19579550
TI  - [Examples of emergency surgery. Ectopic pregnancy, biliary ileus, appendicitis].
AB  - Surgery was practised at home for a long time during the first half of the XXth
      century. The improvement of anaesthesia and of the structures of cares provoked
      the progressive disappearing of these practices after the WWII. Although modern
      techniques were currently used in the Hospitals of the Universities the
      conditions of practising remained the same in some countries at the beginning of
      the century. At the beginning of the 50s before the growing transports surgical
      emergencies could be taken in charge at home in some areas uneasy to reach.

PMID- 19579551
TI  - [Isolation of contagious persons in hospital services].

PMID- 19579552
TI  - [Hospital tents and huts].

PMID- 19579553
TI  - [The persons with venereal diseases in the hospitals of Paris].

PMID- 19579554
TI  - [Temporary hospitals during the plague of 1720 in Provence].

PMID- 19579555
TI  - [Saint-Louis hospital and the plague].

PMID- 19579556
TI  - [Hospitals dealing with contagious diseases from the management of Saint-Andre to
      the construction of Pellegrin].

PMID- 19579557
TI  - [Puerperal fever and hospitals].

PMID- 19579558
TI  - [Hospitals during epidemics in Paris (cholera and typhoid)].

PMID- 19579559
TI  - [Hospitals confronting influenza in 1918-1919: the example in Rouen].

PMID- 19579560
TI  - [Nosocomial infections: behaviors and cultures of the hospitals in question].

PMID- 19579561
TI  - [Risk of actual epidemics: how should one prepare oneself?].

PMID- 19579562
TI  - [The state faces risks of pandemics].

PMID- 19579563
TI  - [Quarantine, at the cross of heterogeneous architectural traditions].

PMID- 19579564
TI  - [Protecting oneself against contagious diseases: preparing the municipal
      disinfection service of Turin (19th, 20th centuries)].

PMID- 19579566
TI  - [Painters in history: the plague of 1720 in Marseille].

PMID- 19579565
TI  - [Epidemics aat the Notre-Dame a la Rose hospital at Lessines in the sixteenth and
      eighteenth centuries].

PMID- 19579567
TI  - [Epidemics in literature].

PMID- 19579568
TI  - Samuel Fernberger's rejected doctoral dissertation: a neglected resource for the
      history of ape research in America.
AB  - I summarize a never-completed 1911 doctoral dissertation on ape behavior by
      Samuel Fernberger of the University of Pennsylvania. Included are observations on
      many behavioral patterns including sensory and perceptual function, learning,
      memory, attention, imagination, personality, and emotion in an orangutan and two
      chimpanzees. There are examples of behavior resembling insight, conscience, tool
      use and imitation. Language comprehension was good but speech production was
      minimal. The document appears to contradict a brief published article on the
      project by William Furness in that punishment was frequently used. The document
      is important for understanding Fernberger's early career, for anticipations of
      later research, and for understanding the status of ape research at the time.

PMID- 19579569
TI  - Was Walter Lippmann interested in stereotyping?: Public Opinion and cognitive
      social psychology.
AB  - Walter Lippmann's Public Opinion is much cited but little read. A review of
      references to Public Opinion by social psychologists over the last 20 years
      reveals the widespread beliefs that (1) the book focuses primarily on group
      stereotypes and prejudice, and (2) the concept of stereotyping originated with
      Lippmann. However, stereotypes, as currently conceived--as opposed to schemata
      more generally--do not play a central role in the book, and Lippmann did not
      introduce the concept (although he may have broadened it). In addition,
      throughout his long and distinguished career, he showed little interest in
      stereotyping, prejudice, and discrimination. Nonetheless, Public Opinion is a
      seminal work in the area of cognitive social psychology and (like other little
      read citation classics) still deserves to be read-including, ironically, by
      students of stereotyping and prejudice.

PMID- 19579570
TI  - Culture and ideology in Ian Suttie's theory of mind.
AB  - The author discusses the comprehensive outlook that shaped Ian Suttie's
      psychology. Suttie is seen as a background influence behind the British school of
      psychoanalysis, and his ideas pervade that school and therefore late-modern
      notions of the mind. The author describes the formation of Suttie's independent
      theory, and argues that his project was expressly ideological, as he tried to
      counter what he saw as the reactionary and disruptive influence of Freud's
      classical theory. Suttie offered an optimistic perception of the mind, which
      could serve as the basis for a progressive social policy. This perception was
      rooted in the outlook of early 20th-century reforming liberalism, whose
      preferences and prejudices it shares.

PMID- 19579571
TI  - Managing the scope and impact of root cause analysis recommendations.
AB  - PURPOSE: Increased public awareness of clinical failure and rising levels of
      litigation are spurring health policy makers in industrialized countries to
      mandate that clinicians report and investigate clinical errors and near misses.
      This paper seeks to understand the value of root cause analysis (RCA)
      recommendations for practice improvement purposes. The paper presents an analysis
      of interviews with nine senior health managers who were asked about their views
      on RCA as practice improvement method. DESIGN/METHODOLOGY/APPROACH: Interview
      data were collected as part of a multi-method evaluation consultancy project
      investigating a local Health Safety Improvement Program. The interview data were
      discourse analysed and arranged into over-arching themes. FINDINGS: The analysis
      reveals rather negative views of the improvement potential of RCA: RCA is subject
      to too many constraints to be able to produce valuable recommendations; RCA
      recommendations: are perceived to be of "variable quality"; generate considerable
      extra work for senior management to do with vetting RCA recommendations; are
      experienced as contributing in only a limited way to organizational and practice
      improvement. RESEARCH LIMITATIONS/IMPLICATIONS: This study focuses on nine
      interviewees only and presents an analysis of single (not multiple) interviews.
      However, these nine interviewees fulfil crucial roles in implementing clinical
      practice improvement initiatives in their respective geographic areas. PRACTICAL
      IMPLICATIONS: The findings suggest that RCA requires much time and negotiation,
      and that the recommendations produced may not live up to the philosophy of
      clinical practice improvement's expectations. It may be necessary to reorient the
      expectations of the power of RCA, or accept that RCA produces communication about
      clinical processes that would otherwise not have taken place, and whose effects
      may not be registering for some time to come. ORIGINALITY/VALUE: Besides drawing
      out the implications for RCA as investigative practice, the analysis argues that
      interviewees' responses harbour indications to suggest that these officials are
      finding themselves engaged in increasing levels of communicative and emotional
      labour, in having to manage and compensate for the ambiguities,
      incommensurabilities and conflicting goals inscribed into "post-bureaucratic"
      initiatives such as RCA.

PMID- 19579572
TI  - The impact of engaging leadership on performance, attitudes to work and wellbeing
      at work: a longitudinal study.
AB  - PURPOSE: The purpose of this paper is to examine the relationship between quality
      of leadership and attitudes to work and a sense of wellbeing at work, and
      organizational performance. DESIGN/METHODOLOGY/APPROACH: This is a longitudinal
      empirical investigation, using quantitative methods. FINDINGS: The findings were
      fourfold: the leadership instrument used was demonstrated to have convergent,
      discriminant and predictive validity; differential relationships were found
      between three aspects of quality of leadership and attitudes to work and a sense
      of wellbeing at work; one leadership QUALITY: "engaging with others"--was shown
      to be a significant predictor of organizational performance; leadership quality
      as assessed by competencies or "capabilities" did not predict performance.
      ORIGINALITY/VALUE: The paper presents evidence of: the validity of a new
      leadership instrument; the differential relationship between leadership quality
      and staff attitudes to work and their sense of wellbeing at work; and a
      predictive relationship between leadership quality and organizational
      performance.

PMID- 19579573
TI  - Transformational, transactional among physician and laissez-faire leadership
      among physician executives.
AB  - PURPOSE: The purpose of this paper is to examine the empirical validity of
      transformational, transactional and laissez-faire leadership and their sub-scales
      among physician managers. DESIGN/METHODOLOGY/APPROACH: A nation-wide, anonymous
      mail survey was carried out in the United States, requesting community health
      center executive directors to provide ratings of their medical director's
      leadership behaviors (34 items) and effectiveness (nine items), using the
      Multifactor Leadership Questionnaire 5X-Short, on a five-point Likert scale. The
      survey response rate was 40.9 percent, for a total 269 responses. Exploratory
      factor analysis was done, using principal factor extraction, followed by promax
      rotation). FINDINGS: The data yielded a three-factor structure, generally aligned
      with Bass and Avolio's constructs of transformational, transactional and laissez
      faire leadership. Data do not support the factorial independence of their
      subscales (idealized influence, inspirational motivation, individualized
      consideration, and intellectual stimulation under transformational leadership;
      contingent reward, management-by-exception active, and management-by-exception
      passive under transactional leadership). Two contingent reward items loaded on
      transformational leadership, and all items of management-by-exception passive
      loaded on laissez-faire. RESEARCH LIMITATIONS/IMPLICATIONS: A key limitation is
      that supervisors were surveyed for ratings of the medical directors' leadership
      style. Although past research in other fields has shown that supervisor ratings
      are strongly correlated with subordinate ratings, further research is needed to
      validate the findings by surveying physician and other clinical subordinates.
      Such research will also help to develop appropriate content of leadership
      training for clinical leaders. ORIGINALITY/VALUE: This study represents an
      important step towards establishing the empirical evidence for the full range of
      leadership constructs among physician leaders.

PMID- 19579574
TI  - Navy Nurse Corps manpower management model.
AB  - PURPOSE: The Navy Nurse Corps is part of a team of professionals that provides
      high quality, economical health care to approximately 700,000 active duty Navy
      and Marine Corps members, as well as 2.6 million retired and family members. Navy
      Nurse Corps manpower management efficiency is critical to providing this care.
      This paper aims to focus on manpower planning in the Navy Nurse Corps.
      DESIGN/METHODOLOGY/APPROACH: The Nurse Corps manages personnel primarily through
      the recruitment process, drawing on multiple hiring sources. Promotion rates at
      the lowest two ranks are mandated, but not at the higher ranks. Retention rates
      vary across pay grades. Using these promotion and attrition rates, a Markov model
      was constructed to model the personnel flow of junior nurse corps officers.
      FINDINGS: Hiring sources were shown to have a statistically significant effect on
      promotion and retention rates. However, these effects were not found to be
      practically significant in the Markov model. Only small improvements in rank
      imbalances are possible given current recruiting guidelines. Allowing greater
      flexibility in recruiting practices, fewer recruits would generate a 25 percent
      reduction in rank imbalances, but result in understaffing. Recruiting different
      ranks at entry would generate a 65 percent reduction in rank imbalances without
      understaffing issues. PRACTICAL IMPLICATIONS: Policies adjusting promotion and
      retention rates are more powerful in controlling personnel flows than adjusting
      hiring sources. These policies are the only means for addressing the fundamental
      sources of rank imbalances in the Navy Nurse Corps arising from current manpower
      guidelines. ORIGINALITY/VALUE: The paper shows that modeling to improve manpower
      management may enable the Navy Nurse Corps to more efficiently fulfill its
      mandate for high-quality healthcare.

PMID- 19579576
TI  - Healthcare governance and organizational barriers to learning from mistakes.
AB  - PURPOSE: The purpose of this article is to advance critical debate in relation to
      a very critical issue in current healthcare management--namely "patient safety".
      This is currently a very high profile issue. In its various guises such as
      clinical governance, integrated governance and healthcare governance the question
      of avoiding or at least minimising harm to patients is attracting a huge amount
      of attention. Considerable resources especially within the acute sector are
      allocated to the problem. But, despite the systematic attention, progress in
      healthcare compared with certain other sectors is slow and mistakes continue to
      occur. Hospital acquired infections and clinical errors have become a matter of
      acute public concern. Evaluations of the health service are critically influenced
      by adverse judgements on this dimension of care. DESIGN/METHODOLOGY/APPROACH: The
      authors draw primarily upon relevant literature in order to make sense of recent
      empirical research in eight acute hospital trusts in the UK. The analysis,
      however, is relevant to healthcare systems around the world. FINDINGS: The
      authors reveal how the massive investment in systems, service improvement
      mechanisms and clinical government regimes may not in themselves be enough. One
      reason why they may not be enough is that there can be a problem of gaining
      acceptance and legitimacy. Staff may see such managers as "policing" and
      "interfering". There is then the danger of a vicious circle--more control but
      less effective control because of a feeling of alienation. The policing element
      is at best a final safety net not the prompt for improvement. They then identify
      six barriers and each is accompanied by a recommendation for its resolution.
      PRACTICAL IMPLICATIONS: There are a number of implications for practice and for
      systems reform, which stem from the analysis. Two main recommendations stand out:
      they need to be handled together. First, the traditional model of the autonomous
      professional needs to be challenged by subjecting clinical practice to shared
      clinical governance procedures. Second, and simultaneously, there is a need to
      attend to underlying values. There is a need to revisit the issue of underpinning
      values so that clinical values and system-wide/managerial values are congruent
      rather than separate or even in conflict. At this point, governance and
      leadership should come together. ORIGINALITY/VALUE: This paper provides useful
      information from the literature on current healthcare management.

PMID- 19579575
TI  - Health care competition, strategic mission, and patient satisfaction: research
      model and propositions.
AB  - PURPOSE: In all industries, competition among businesses has long been encouraged
      as a mechanism to increase value for patients. In other words, competition
      ensures the provision of better products and services to satisfy the needs of
      customers This paper aims to develop a model that can be used to empirically
      investigate a number of complex issues and relationships associated with
      competition in the health care industry. DESIGN/METHODOLOGY/APPROACH: A
      literature review was conducted. A total of 50 items of literature related to the
      subject were reviewed. Various perspectives of competition, the nature of service
      quality, health system costs, and patient satisfaction in health care are
      examined. FINDINGS: A model of the relationship among these variables is
      developed. The model depicts patient satisfaction as an outcome measure directly
      dependent on competition. Quality of care and health care systems costs, while
      also directly dependent on the strategic mission and goals, are considered as
      determinants of customer satisfaction as well. The model is discussed in the
      light of propositions for empirical research. PRACTICAL IMPLICATIONS: Empirical
      studies based on the model proposed in this paper should help identify areas with
      significant impact on patient satisfaction while maintaining high quality of
      service at lower costs in a competitive environment. ORIGINALITY/VALUE: The
      authors develop a research model which included propositions to examine the
      complex issues of competition in the health care industry.

PMID- 19579577
TI  - [Surgical treatment of back problems of a growing child].
AB  - During the years when a child is developing, the most common problems requiring
      surgical treatment of the back are scoliosis and spondylolisthesis of various
      causes. Spinal tumors and bacterial inflammations of the vertebrae or
      intervertebral disks occur rarely in children. Due to spinal injury,
      approximately 20 children require surgical treatment annually. The possibility of
      instability of the cervical spine should be taken into account especially in
      connection with anesthesia procedures in children with Down's syndrome and those
      suffering from disturbances of skeletal development.

PMID- 19579578
TI  - [Long term oxygen therapy: many hopes, little proof].
AB  - Long-term oxygen therapy extends the life span of hypoxemic patients with chronic
      obstructive pulmonary disease (COPD). The patients often have great expectations
      concerning the quality of life, but oxygen therapy does neither relieve dyspnea
      nor reduce the need for hospital treatments. Oxygen therapy in diseases other
      than COPD lacks scientific basis. It is worthwhile to start in-hospital oxygen
      therapy by determining the oxygen flow with a device given to the patient, and
      the effect of the therapy on the nocturnal accumulation of carbon dioxide is
      checked. In the future, focus should be on other forms of therapy, such as
      rehabilitation.

PMID- 19579579
TI  - [Gender differences in brain development--correlation with the spectrum of
      psychiatric disturbances].
AB  - Maturation of brain structure has a different rhythm in girls and boys. From the
      viewpoint of cognitive processes, the first decade of life is the most important
      developmental stage after intrauterine life, cognitive functions will essentially
      develop also during the second decade. Gender differences have been noted already
      in early adolescence. Behavioral disturbances and substance abuse problems as
      well as attention-deficit disorders are more common in boys, whereas depression,
      anxiety and eating disorders are more common in girls. Regarding psychiatric
      morbidity, onset of puberty and late adolescence are periods of special
      vulnerability.

PMID- 19579580
TI  - [Can the recurrence of alcohol-induced pancreatitis be prevented?].
AB  - 70% of pancreatitis cases are considered to be induced by alcohol. Half of those
      fallen ill with alcohol-induced acute pancreatitis will have relapses. A
      prospective follow-up study showed that the level of dependence on alcohol
      constitutes the most important risk factor. Continued drinking was shown to be a
      dose-responsive risk factor for relapse; abstinence provided for a complete
      protection against renewed pancreatitis. In a randomized study, a semi-annual
      meeting with a healthcare professional specialized in substance abuse problems
      significantly reduced new episodes of acute pancreatitis. It is thus possible to
      at least reduce relapses by intervening in the risk factors.

PMID- 19579581
TI  - [Demyelinating lesions as an incidental finding in magnetic resonance imaging of
      the brain--what shall I tell the patient].
AB  - Incidentally found brain lesions will increase as magnetic resonance imaging of
      the brain becomes more common. What should be told to a patient, who has
      undergone brain imaging e.g. for headaches, and the image reveals lesions
      compatible with multiple sclerosis? A demyelinating lesion should be related with
      the patient's age, other diseases, earlier symptom history and results of a
      clinical neurological examination. Multiple sclerosis cannot be diagnosed merely
      based on magnetic resonance imaging. Clinical monitoring is required if a
      significant number of plaques typical of multiple sclerosis is present.

PMID- 19579582
TI  - [Occupational asthma in a structure nail maker].
AB  - Chemicals that may cause allergy are being used in structure nails. In this case
      report two structure nail makers are described, who were diagnosed with
      occupational asthma in clinical studies. The studies included an inhalational
      exposure simulating the work. The causative agents of occupational asthma are
      apparently the acrylate compounds contained in the chemicals; use of these
      compounds has previously been linked with allergic contact dermatitis and asthma.
      Since the making of structure nails involves health risks, such work requires
      appropriate premises and personal protection.

PMID- 19579583
TI  - Pancreaticojejunostomy after pancreaticoduodenectomy: results of a new technique.
AB  - BACKGROUND/AIMS: Pancreaticoduodenectomy is the standard treatment for
      periampullary tumors. One of the major causes of morbidity after
      pancreaticoduodenectomy is the failure of the healing at the pancreaticoenteric
      anastomosis. The aim of this study is to summarize the results of a new technique
      which is designed to decrease the panreticoje-junostomy anastomotic leakage.
      METHODOLOGY: The demographic characteristics, operation indications, types of the
      pancreaticoduodenectomy, duration of the postoperative hospitalization, morbidity
      and mortality of the consecutive patients whose pancreaticojejunostomy
      anastomosis after pancreaticoduodenectomy was performed by modified invagination
      method at Hacettepe University Medical School Department of General Surgery
      between February 2005 and December 2007 were evaluated prospectively. RESULTS:
      Thirtyone patients were included in the study. The operation indications were
      pancreas cancer for 17 patients, ampulla Vateri cancer for 8 patients, duodenum
      cancer for 3 patients, cancer of the distal choleduct for 2 patients and gall
      bladder cancer for 1 patient. Twenty complications had occurred in a total of 15
      patients. There were no pancreaticojejunostomy anastomotic leakage and mortality
      in any of the patients. CONCLUSIONS: An ideal pancreaticojejunostomy anastomosis
      after pancreaticoduodenectomy should be safe, simple and secure. This modified
      invagination method seems to be promising when these parameters are taken in to
      account.

PMID- 19579584
TI  - Improving quality of magnetic resonance cholangiopancreaticography: esomeprazole
      versus ranitidine.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the effect of Ranitidine
      and Esomeprazole on the pancreatico-biliary tree and to define their role in
      improving visualization quality on magnetic resonance cholangiopancreaticography
      images. METHODOLOGY: Magnetic resonance cholangiopancreaticography was done on 70
      volunteers before and after using ranitidine for half of them and esomeprazole
      for the other half of the group. The images were evaluated for contrast effect
      (signal from stomach and duodenum), and image effect (conspicuousness) at various
      segments of pancreaticobiliary tree. RESULTS: Improvement of Contrast effect on
      stomach and duodenum in Esomeprazole group was 72.5% and in Ranitidine group was
      28.6%. While image effect of pancreatic duct for Esomeprazole was 60% and for
      Ranitidine was 17.1%, and their statistical results were in concordance with p
      value (< 0.01), but the image effect of the biliary tree didn't show any
      significant improvement or difference between imaging and statistical results.
      CONCLUSION: Esomeprazole is superior to Ranitidine in improving the quality of
      Magnetic Resonance Cholangiopancreaticography images especially the contrast
      effect of duodenum and stomach and image effect of pancreatic duct.

PMID- 19579585
TI  - Prognostic factors for radical resection of middle and distal bile duct cancer.
AB  - BACKGROUND/AIMS: Prognostic factors after radical operation for middle and distal
      bile duct cancer are not fully understood. The aim of this study is to identify
      prognostic factors for patients undergoing radical operation for middle and
      distal bile duct cancer. METHODOLOGY: The records of 57 patients with middle
      (n=22) and distal (n=35) bile duct cancer who had undergone radical surgery were
      reviewed (pancreaticoduodenectomy in 46 patients, extrahepatic bile duct
      resection in 6, and major hemihepatectomy in 5). The clinicopathological
      prognostic factors affecting survival were examined. RESULTS: The 5 years
      survival rate was 36% (median survival time, 34 months). Significant prognostic
      factors according to univariate analysis include pT classification, papillary
      type, number of metastatic lymph node, positive radial margin, pancreatic
      invasion, lymphatic invasion, venous invasion, common hepatic node metastasis,
      paraaortic node metastasis, and combined vascular resection. Independent
      significant prognostic factors according to multivariate analysis include the
      number of metastatic lymph nodes (5 or more), positive radial margin, and common
      hepatic node metastasis. CONCLUSIONS: The number of metastatic lymph nodes,
      common hepatic node metastasis, and positive radial margin are independent
      prognostic factors for middle and distal bile duct cancer. The surgical treatment
      of middle and bile duct cancer should achieve a negative radial margin for a
      favorable outcome.

PMID- 19579586
TI  - Clinical significance of measuring urinary sulfated bile acids in adult patients
      with hepatobiliary diseases.
AB  - BACKGROUND/AIMS: Measurement of urinary sulfated bile acid (USBA) level is a
      simple urine test that reflects the degree of cholestasis in newborns. The aim of
      this study was to clarify the clinical significances of this test for liver
      diseases in adults. METHODOLOGY: We examined the relationship between USBA level
      in a urine sample by enzymatic assay and clinical parameters and postoperative
      complications in 27 patients with hepatobiliary diseases who underwent surgical
      procedures between 2002 and 2007. RESULTS: Mean USBA in all patients before
      surgery was 39.8 +/- 64.0 micromol/L (median value was 6.6). USBA level was
      increased in patients with cholestasis. USBA level was significantly correlated
      with serum total bile acid, total bilirubin level and serum hyaluronic acid level
      (r = 0.850, 0.602 and 0.504, respectively) (p < 0.05) and, furthermore, tended to
      be correlated with liver-uptake ratio (LHL15) by technetium-99m galactosyl human
      serum albumin (99SmTc-GSA) scintigraphy and alanine aminotransferase level (r = 
      0.469 and 0.436, respectively but not significant). USBA level tended to be
      associated with postoperative uncontrolled ascites (p = 0.050, not significant).
      Postoperative USBA level by day 7 was not changed; however, USBA level in
      patients with cholestatic diseases was decreased. CONCLUSIONS: USBA is a simple
      and sensitive noninvasive test for cholestasis and also useful to predict
      postoperative uncontrolled ascites after hepatic resections.

PMID- 19579587
TI  - Cholecystectomy for gallbladder disease in elderly aged 80 years and over.
AB  - BACKGROUND/AIMS: Patients aged 80 years and over show greater risk of complicated
      gallbladder diseases and associated comorbidities. The aim of the study is to
      evaluate the prognosis after laparoscopic or open cholecystectomy in these
      patients. METHODOLOGY: 100 patients aged between 80 and 92 years (group 1) and
      241 patients aged between 70 and 79 years (group 2), undergoing cholecystectomy
      for gallbladder disease, are the subject of the study. Types of disease and
      surgery and p.o. morbidity and mortality have been evaluated. RESULTS: The
      patients of group 1 have shown a significant greater incidence of p.o. morbidity
      (20%) than group 2 (2.3%) (chi2 = 39.5; p < 0.001), regardless to the type of
      cholecystectomy. Endoscopic sphincterotomy for lithiasis of common biliary duct
      seems an important risk factor (chi2 = 7.1; p < 0.001). In group 2, the morbidity
      rate after laparoscopic cholecystectomy was lesser than after open surgery
      (X2=5.3; p < 0.02). In both groups, postoperative hospital stay was longer after
      open cholecystectomy and endoscopic sphincterotomy. CONCLUSIONS: Patients aged 80
      years and over, undergoing cholecystectomy, specially after endoscopic
      sphinterotomy., have a greater risk of p.o. morbidity and mortality than younger.
      Laparoscopic and open cholecystectomy seems to bear the same poor p.o. prognosis.

PMID- 19579588
TI  - Usefulness of gemcitabine combined with 5-fluorouracil and cisplatin (GFP) in
      patients for unresectable biliary carcinoma.
AB  - BACKGROUND/AIMS: Advanced biliary carcinoma have poor prognosis and chemotherapy
      has been shown to have little impact. The aim of the present study is to clarify
      the effectiveness of GEM combined with CDDP and 5FU (GFP) therapy for
      unresectable biliary carcinoma. METHODOLOGY: Fourteen patients with biliary
      carcinoma (4 patients; gallbladder cancer, 10 patients; biliary tract) who had no
      prior chemotherapy were enrolled. A triple combination of agents was administered
      with a 4-week cycle GFP chemotherapy consisting of GEM at 1000 mg/m2 on days 1
      and of 5-FU at 250 mg/m2 and CDDP at 3mg/m2 on days 1 to 5. RESULTS: No patient
      achieved CR, while five patients achieved PR as assessed by RECIST. The overall
      response rate from the intent-to-treat analysis was 21.4%. Stable disease was
      observed in 9 (64.3%) patients. Clinical benefit rate was observed in 14 (85.7%)
      patients. According to the tumor site, overall response rate was 20.0% in biliary
      tract carcinoma, on the other hand, 25.0% in gallbladder carcinoma. CONCLUSIONS:
      The significant antitumor activity of GFP chemotherapy has been seen in patients
      with advanced biliary carcinoma. However, further evaluation in large numbers of
      patients is needed to determine the difference in chemosensitivity according to
      the tumor site.

PMID- 19579589
TI  - Length of vancomycin administration for treatment of clostridium difficile
      associated diarrhea may depend on presentation of colonic ulcer.
AB  - BACKGROUND/AIMS: Clostridium difficile-associated diarrhea (CDAD) is a notorious
      iatrogenic infection with typical endoscopic features consisting of
      pseudomembranes (PMs). Concomitant colonic ulcers are sometimes endoscopically
      detected. We hypothesized that length of vancomycin (VCM) administration for
      treatment depends on presentation of colonic ulcer. METHODOLOGY: We investigated
      retrospectively endoscopic findings and total number of days of vancomycin
      administration for patients who showed evidence of C. difficile toxin A or PMs at
      our hospitals. We excluded CDAD cases with inflammatory bowel disease. RESULTS:
      Sixteen patients were diagnosed as having CDAD. All patients receiving endoscopic
      examination presented PMs. Two cases had PMs in the transverse and small
      intestine. The patients with ulcers needed 5-28 days of administration of VCM,
      while all those without ulcers except one were cured within seven days.
      CONCLUSIONS: Our results suggest that ulcer may be a factor of poor prognosis,
      and we recommend endoscopic examination for all patients with CDAD for
      identification of poor prognostic groups.

PMID- 19579590
TI  - Preoperative tumor markers as prognostic factors of colorectal liver metastases.
AB  - BACKGROUND/AIMS: Tumor recurrence develops in 45-80% of patients after liver
      surgery for colorectal liver metastases. To assess the significance of
      preoperative tumor marker levels for disease free interval (DFI) and patient
      survival (PS) after liver surgery. METHODOLOGY: Preoperative serum levels of
      carcinoembryonic antigen--CEA, CA 19-9, CA 72-4, thymidine kinase (TK), tissue
      polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) were
      evaluated in 173 patients operated on for colorectal liver metastases (CLM).
      Liver resection was performed on 114 patients and radiofrequency ablation on 59
      patients. RESULTS: Preoperative serum levels of TPA (cut off level = 53 IU/L,
      Hazard ratio = 4.5, Wilcoxon test: p < 0.01, Log-Rank test: p < 0.03) and TPS
      (cut off level = 81 IU/L, Hazard ratio = 5.1, Wilcoxon test: p < 0.007, Log-Rank
      test: p < 0.009) were important for PS and DFI after liver resection (TPA: cut
      off level = 53 IU/L, Hazard ratio = 3.5, Wilcoxon test: n.s., Log-Rank test:
      n.s.; TPS: cut off level = 81 IU/l, Hazard ratio = 2.6, Wilcoxon test: p < 0.02,
      Log-Rank: p < 0.06). TPA serum levels were important for PS (Wilcoxon test--p <
      0.003, Log-Rank test--p < 0.0002) and DFI after RFA (Wilcoxon test--p< 0.001, Log
      Rank Test--p < 0.0001). TPS serum levels also correlated with PS (Wilcoxon test-
      p < 0.005, Log-Rank test--p < 0.003) and DFI after RFA (Wilcoxon test--p < 0.001,
      Log-Rank Test--p< 0.0001). CONCLUSIONS: TPA and TPS are important predictive
      markers for PS and DFI after liver resections and radiofrequency ablations for
      CLM.

PMID- 19579591
TI  - Enteral nutrition improves health-related quality of life in Crohn's disease
      patients with long disease duration.
AB  - BACKGROUND/AIMS: Although enteral nutrition therapy has been highlighted as
      maintenance therapy for Crohn's disease, few reports have investigated the impact
      of enteral nutrition on the health-related quality of life of Crohn's disease
      patients. METHODOLOGY: We cross-sectionally evaluated the effect of multiple
      clinical factors including enteral nutrition on the health-related quality of
      life of Crohn's disease patients focusing on patient disease duration using the
      Inflammatory Bowel Disease Questionnaire. RESULTS: Of all 126 patients examined,
      95 patients were receiving enteral nutrition. Multiple linear regression analysis
      using 18 clinical parameters revealed that disease activity was a dominant factor
      that affected the health-related quality of life of Crohn's disease patients, and
      that enteral nutrition was also an independent factor that improved the
      Inflammatory Bowel Disease Questionnaire total score, bowel symptoms, and
      systemic symptoms for patients with a disease duration of 10 years or more (P =
      0.0090, 0.0033, and 0.016, respectively). CONCLUSIONS: Enteral nutrition improved
      the health-related quality of life of Crohn's disease patients with long-term
      disease duration. Thus, enteral nutrition should be recommended as one of the
      options for maintenance therapy for Crohn's disease.

PMID- 19579592
TI  - Liver fibrosis and hepatic stellate cells improvement of chronic hepatitis C
      patients by interferon-beta-1a with or without sustained viral response.
AB  - BACKGROUND/AIMS: We aimed to assess liver fibrosis in biopsies from patients with
      chronic hepatitis C and relationship to different responses to interferon-beta
      la. METHODOLOGY: 21 patients with chronic hepatitis C were divided into two
      groups randomly and treated with recombinant human interferon-beta-la (IFN-B-1a)
      or IFN-beta-1a plus ribavirin (RBV) for 24 weeks, then followed up for another 24
      weeks. 42 liver biopsies of 21 patients before and after treatment respectively
      were evaluated on conventional histological assessment. Then we studied 21
      patients liver biopsies by immunohistochemical analysis of alpha-smooth muscle
      actin (alpha-SMA) and collagen type III. RESULTS: A significant improvement in
      HAI fibrosis staging was detected after therapy in all sustained viral responders
      (SVR) and non-responders (NR) patients. The percentages of cases with HAI scores
      and fibrosis staging decreased obviously were 100.0% and 71.4% in SVR patients
      and 50.0% and 42.9% in NR patients. The patients with combination therapy or
      normal ALT on 48w would more often receive the HAI and fibrosis staging decrease.
      The significantly lower alpha-SMA-positive HSCs and mean expression level of
      collagen type III were detected in the post-treatment biopsies. The HAI, alpha
      SMA, collagen type III values were significantly correlated with the values of
      the semiquantitative indexes of fibrosis. CONCLUSIONS: IFN-beta-1a therapy is
      effective for patients with chronic hepatitis C on liver histology regardless of
      viral response. The alpha-SMA-positive HSCs and collagen type III expression are
      responsible for liver fibrosis.

PMID- 19579593
TI  - Fourteen-years of disease-free survival in a patient with advanced gallbladder
      carcinoma after radical resection: a case report.
AB  - We describe a case of advanced gallbladder carcinoma (GBC) with extensive local
      invasion that has had 14-years of disease-free survival after complete resection.
      A 53-year-old woman was referred to our hospital with right hypochondriac pain
      and constipation. A preoperative diagnosis of advanced GBC with invasion into the
      liver bed, the abdominal wall, the duodenum, the common bile duct and the hepatic
      flexure of the colon were made. It was performed an extensive en bloc resection
      of the GBC, which included a cholecystectomy, resection of the associated liver
      bed, pancreatoduodenectomy, right hemicolectomy and resection of the anterior
      abdominal wall. On histopathology, the resected specimen showed a well
      differentiated adenocarcinoma and the 56 resected lymph nodes showed no evidence
      of metastasis. Twelve-years after the above procedure, a laparotomy was performed
      for ileus; however, no macroscopic evidence of cancer recurrence was found in the
      peritoneal cavity.

PMID- 19579595
TI  - Oxidative stress and tumor progression in colorectal cancer.
AB  - BACKGROUND/AIMS: Elevated oxidative status has been found in many types of cancer
      cells. Recent studies have shown that the enzymatic product of thymidine
      phosphorylase (TP) generated reactive oxygen species (ROS) within cancer cells.
      The aim of this study was thus to evaluate the signal transduction pathway and
      the role of ROS in colorectal cancer. METHODOLOGY: Blood specimens were obtained
      from the drainage vein of the tumor during operation in 76 patients with
      colorectal cancer. Serum ROS levels were measured using the derivative-Reactive
      Oxygen Metabolites (d-ROM) test and serum TP levels were examined by a highly
      sensitive ELISA method. RESULTS: There was no significant correlation between
      serum levels of ROS and TP. Serum ROS levels were elevated in proportion to tumor
      invasion and had a significant positive correlation with tumor size (p < 0.05).
      However, they did not increase in patients with liver metastasis. CONCLUSIONS:
      These findings suggest that ROS are independent of TP-triggered signaling
      transduction and are associated with increased tumor invasion, but not liver
      metastasis in patients with colorectal cancer. From this point of view, new
      strategies related to ROS may provide improved therapeutic results as well as a
      preventative effect on carcinogenesis of the colorectum.

PMID- 19579594
TI  - Colon cancer releases alpha-tocopherol from its O-glycosides better than normal
      colon tissue.
AB  - BACKGROUND/AIMS: Free radicals, in a colon, may damage DNA, make difficult DNA
      repair and change course of post-translational modifications of regulatory
      proteins, which promote tumor initiation and progression. Therefore risk of colon
      cancer is closely related to diet and other lifestyle factors. Dietary
      antioxidants, such as vitamin E, should reduce the levels of harmful oxidation
      products. However vitamin E is not soluble in water, which decreases its
      bioavailability. As O-glycosides of alpha-tocopherol are better soluble in water
      and penetrate to tissues easier than free alpha-tocopherol, the aim of our work
      was to investigate the rate of release the free tocopherol from its O-glycosides
      in colon cancer, in comparison to human healthy colon tissue. METHODOLOGY: The
      activities of enzymes catalysing hydrolysis of alpha-tocopheryl glucoside (1a)
      and mannoside (1b) as well as p-nitrophenyl beta-glucoside (2a) and mannoside
      (2b) in cancer and healthy human colon tissues, were determined according to the
      modified method described by Zwierz et al. RESULTS: The alpha-tocopherol and p
      nitrophenol were significantly better released from the respective glucosides and
      mannosides in cancer tissue than in "healthy" human colon tissues, with p =
      0.000947 for la, p = 0.033024 for 1b; p = 0.0028 for 2a, and p = 0.0033 for 2b,
      respectively. CONCLUSION: Alpha-tocopherol and p-nitrophenol are released from
      the O-glycosides of glucose and mannose in significantly higher amount in colon
      cancer than in healthy tissues. The alpha-tocopherol O-glycosides can be
      considered as prodrugs in prevention and treatment of the colon cancer.

PMID- 19579596
TI  - Plasma level of granulocyte-colony stimulating factor during granulocyte and
      monocyte adsorptive apheresis in patients with ulcerative colitis.
AB  - BACKGROUND/AIMS: Cytapheresis with extra-corporeal circulation for ulcerative
      colitis is effective but its mechanisms are still unclear. Granulocytecolony
      stimulating factor (G-CSF) strongly mobilizes bone marrow-derived cells and
      serves as antiinflammatory factor. We investigated plasma levels of G-CSF during
      granulocyte and monocyte adsorptive apheresis (GCAP). METHODOLOGY: Nineteen cases
      of ulcerative colitis were measured plasma concentration of G-CSF during the
      first session of GCAP therapy. RESULTS: G-CSF were significantly increased in the
      column inflow at 30 min compared with the baseline (Wilcoxon test, p < 0.01), and
      also increased through the column (Wilcoxon test, p < 0.01). The ratio of the
      increase in the column outflow at 60 min was 1.5-fold compared with the baseline.
      However, we could not show a significant relation between G-CSF level and
      clinical efficacy. CONCLUSIONS: This is the first report concerning G-CSF during
      CAP. G-CSF is increased due to GCAP and appears to be a candidate which should be
      further investigated.

PMID- 19579597
TI  - Colorectal stapling anastomosis without transanal procedure for anterior
      reseciton.
AB  - BACKGROUND/AIMS: We reported a novel surgical technique, sliding functional end
      to-end anastomosis (SFEEA), which abrogates the need for the transanal procedure
      for colorectal anastomosis. The aim of this study is to evaluate to the
      usefulness of SFEEA in high anterior resection as compared with double stapling
      technique (DST). METHODOLOGY: From 2001 to 2005, high anterior resection was
      performed in 78 consecutive patients with advanced sigmoid colon cancer whose
      anatomoses with stapler were located under their promontories using SFEEA (n=35)
      or DST (n=43). We reviewed their medical records for operative duration,
      intraoperative blood loss, postoperative complications and suture line recurrence
      retrospectively. RESULTS: The operation time was a median of 85 (range 60-150)
      minutes for the SFEEA group compared with 130 (range 60-180) minutes for the DST
      group (p < 0.001). Intraoperative blood loss was a median of 60 (range 10-520) ml
      for the SFEEA group compared with 40 (range 10-600) ml for the DST group. In the
      DST group, two postoperative complications (5%) occurred, leakage and stenosis
      respectively, compared with no complications in the SFEEA group. Only one suture
      line recurrence (2%) occurred in the DST group compared with no recurrence in the
      SFEEA group. CONCLUSION: In high anterior resection, SFEEA is easy, safe and
      useful as compared with DST.

PMID- 19579598
TI  - Silencing hexokinase II gene sensitizes human colon cancer cells to 5
      fluorouracil.
AB  - BACKGROUND/AIMS: Extensive trials have indicated that cancer cells with high
      glycolytic activity exhibit decreased sensitivity to anticancer agents. Moreover,
      recent research has proved that a specific inhibitor of hexokinase II, which is a
      key glycolytic enzyme, may enhance the activity of anticancer drugs. The purpose
      of this study is to further investigate the effect and mechanisms of hexokinase
      II on chemosensitivity of colon cancer cells to 5-fluorouracil. METHODOLOGY: The
      expression of hexokinase II gene was down regulated by RNA interference in colon
      cancer cell line LoVo, then the IC50 value of 5-fluorouracil to LoVo cells was
      carried out by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      and the protein expression of hexokinase II and thymidylate synthas by Western
      blot analysis Meanwhile, cell apoptosis and mitochondrial membrane potential were
      assessed by flow cytometry. Caspase-3 activity was also determined by its
      substrate color reaction. RESULTS: Down-regulation of the hexokinase II gene of
      LoVo cells resulted in decreased IC50 value of 5-fluorouracil and increased
      apoptosis rate, respectively. Furthermore, silencing hexokinase II of LoVo cells
      induced loss of mitochondrial membrane potential, activation of caspase-3, and
      inhibition of thymidylate synthase expression. CONCLUSIONS: Our findings suggest
      targeting hexokinase II has a potential role in the combination 5-fluorouracil
      treatments of colon cancer.

PMID- 19579599
TI  - Utility of serum preoperative carcinoemberyonic antigen in colorectal cancer
      patients.
AB  - BACKGROUND/AIMS: The usefulness of preoperative CEA in CRC remains controversial
      as regards its biological function, and its use in the diagnosis, prognosis, and
      management and follow up of CRC patients. the aim of this study was to provide a
      critical and updated study for the value of CEA in CRC. METHODOLOGY: From January
      2000 to June 2005, a prospective randomized study involving 200 CRC patients for
      whom curative resection was performed, another 100 healthy persons as a control
      group was included. Basal CEA using chemilumescence technique and routine follow
      up were done. RESULTS: (1) The mean basal CEA in CRC patients (17.3 ng% +/- 1.67)
      was significantly higher than control (3.41 ng% +/- 1.1). (2) A significant
      linear association between basal CEA and Dukes' classes was evident with the mean
      basal CEA for Dukes' A, B, C were 7.8, 12.7, 25.8 respectively (expressed as
      ng%). (3) The validity of basal CEA in primary CRC diagnosis was highly positive
      (sensitivity 80%--PPV 86.95%--accuracy 73.66%), with hig her efficacy in advanced
      disease detection (sensitivity 93%--NPV 7%--accuracy 84.5%--odds ratio 30.3) and
      negative exclusion power for DFS prediction (specificity 13.84%). (4) The basal
      CEA was a discriminate factor in colorectal prognosis - B value (3.74). (5)
      Patients with CEA < or =5 ng% had better DFS (15%) and DFT (23.6 months) than
      those with CEA > 5 ng% as they had DFS (33.75%) and DFT (18.48 months). (6) Basal
      CEA above 15 ng% had a significant shift in the cumulative hazard of recurrence.
      CONCLUSION: The CEA is a metastasis potentiator. The high serum CEA in CRC
      screening programs should be considered a marker of malignancy especially in
      patients with appropriate symptoms. The preop CEA in CRC patients identifies
      subsets with favorable, indolent and uneven biological behavior (< or =5 ng%, <
      or =15 ng%, > 15 ng% respectively). Moreover, the addition of preop CEA level to
      conventional staging forms a strong prognostic tool and supplies adopted practice
      guideline initiative for follow up and therapy in CRC.

PMID- 19579600
TI  - Prognostic role of vascularisation and proliferation in rectal cancer with liver
      metastasis.
AB  - BACKGROUNDS/AIMS: The present study was designed to provide an analysis of
      factors for tumor vascularisation and proliferation in 37 rectal cancer patients
      with concurrent and recurrent liver metastasis underwent preoperative
      radiotherapy, surgery and adjuvant chemotherapy with emphasis on the time of
      presence of hepatic spread. METHODOLOGY: Immunohistochemistry was used for
      expression of proliferation (MIB-1) and for detection of microvessel density
      (MVD, expressed by CD34). Clinicopathological findings were compared with outcome
      with emphasis on IHC. RESULTS: A vascular enumeration, pN status and the time of
      presence of the metastases has shown prognostic role along with the factors
      above. Increased proliferative activity of the tumor as expressed by MIB-1
      staining had no prognostic value, similarly to the localization of tumor, gender,
      age or grading. CONCLUSION: Higher pN status and tumor vascularisation has been
      linked to poor prognosis in overall survival and recurrence of liver metastases.

PMID- 19579601
TI  - Relationship between MVD and meshed-capillaries using magnifying NBI colonoscopy
      in colorectal precursor lesions.
AB  - BACKGROUND/AIMS: To prospectively investigate differences in angiogenesis between
      low-grade dysplasia (LGD) and hyperplastic polyps, as well as the relationship
      between microvessel density (MVD) as identified by histological analysis and
      meshed-capillary (MC) vessels visualized using magnifying narrow band imaging
      (NBI) colonoscopy. METHODOLOGY: Immunohistochemical analysis of MVD was performed
      using monoclonal antibody against CD31. The number and thickness of vessels were
      investigated for 45 LGD and 25 hyperplastic polyps. In contrast, NBI colonoscopy
      was able to classify all lesions into either visualization or nonvisualization of
      MC vessels. RESULTS: No significant difference was seen in the number of thin
      vessels (< or =10 microm) using immunohistochemical MVD analysis between LGDand
      hyperplasic polyps (p = 0.36). In contrast, the number of intermediate (11-20
      microm) and thick vessels (> or =21 microm) differed significantly between LGD
      and hyperplasic polyps, respectively (p < 0.0001, p < 0.0001). In NBI findings,
      the presence of MC vessels was found in 98% (44 of 45) of LGD, while MC vessels
      were absent in 92% (23 of 25) of hyperplasic polyps. CONCLUSIONS: We postulated
      that the incidence of intermediate and thick vessels (>10 microm) is related to
      angiogenesis occurring during carcinogenesis of colorectal mucosa. Furthermore,
      the appearance of visualized MC vessels during magnifying NBI colonoscopy can be
      used to identify angiogenesis in colorectal LGD and hyperplastic polyps.

PMID- 19579602
TI  - Laparoscopic assisted intersphincteric resection following preoperative
      chemoradiation therapy for locally advanced lower rectal cancer: report of a
      case.
AB  - Laparoscopy-assisted surgery for rectal surgery has been shown to be both
      technically feasible and a safe alternative to laparotomy. It can be combined
      with preoperative chemoradiation and sphincter preserving operation for advanced
      low rectal cancer. We report a case of advanced lower rectal cancer, which was
      treated with laparoscopy-assisted total mesorectal excision and intersphincteric
      resection (abdomino-anal resection with coloanal anastomosis) following
      preoperative chemoradiation. In this patient, preoperative chemoradiation was
      very effective and no cancer cells remained in resected specimens.

PMID- 19579603
TI  - Anastomotic stricture of Billroth-I gastroduodenostomy using a hemi-double
      stapling technique.
AB  - BACKGROUNDS/AIMS: Although the hemi-double stapling (HDS) technique is one of the
      methods of mechanically stapled anastomosis for Billroth-I (B-I)
      gastroduodenostomy, the development of anastomotic strictures has not been
      discussed adequately. Thus, we performed a retrospective study to compare the
      anastomotic stricture of the HDS and the hand-sutured anastomosis (HSA)
      technique. METHODOLOGY: We selected 74 early gastric cancer patients in whom B-I
      reconstruction was performed under laparotomy after distal gastrectomy. The
      patients were divided into 2 groups: HDS (34 patients) and HSA (40 patients).
      Several parameters such as time required for achieving anastomosis, operative
      blood loss, the rate of anastomotic stricture formation, time to resumption of
      oral intake, and postoperative complications were examined. RESULTS: There was no
      difference between the 2 groups with regard to operative blood loss, time to
      resumption of oral intake, and postoperative complications. The time required for
      the operation and for achieving anastomosis was shorter in the HDS group than in
      the HSA group. The rate of anastomotic stricture formation was not significantly
      different between the 2 groups, but was lower in the HDS group than in the HSA
      group. CONCLUSIONS: We conclude that the HDS technique reduces the duration of
      operation and the rate of anastomotic stricture formation.

PMID- 19579604
TI  - The clinical usefulness of the ZAP classification for non-erosive reflux disease
      (NERD), using distal esophageal biopsy.
AB  - BACKGROUND/AIM: It has been reported that the Z-line appearance (the ZAP grade)
      wascorrelated with the prevalence of intestinal metaplasia. Therefore, we
      prospectively investigated the clinical usefulness of ZAP classification based on
      the histology in making a diagnosis of non-erosive reflux disease (NERD).
      METHODOLOGY: We studied 80 consecutive young male patients with heartburn and
      acid regurgitation. The symptom characteristics were collected by interviewing
      with a structured questionnaire. Upper GI endoscopy with biopsy was performed to
      identify the distal esophagitis. RESULTS: Correlation was significant between the
      ZAP score and the LA classification (Spearman cor relation factor: 0.463). There
      were no significant differences in symptom according to the ZAP score. There were
      no significant differences in microscopic esophagitis between the patients with
      NERD (ZAP 0) and those with ERD (Erosive Reflux Disease, ZAP I, II, III). No
      statistical significance was observed between the ZAP score and the histology. In
      the diagnosis of NERD, ZAP classificationwas more accurate than LA classification
      in the basis of histology at distal esophagus (p < 0.05). CONCLUSIONS: The ZAP
      classification could be applied to diagnosis of GERD, especially NERD. Biopsy
      taken at distal esophagus can be a limited but useful diagnostic tool,
      particularly in patients with NERD.

PMID- 19579605
TI  - Double-blind randomized multicenter study comparing the efficacy and safety of 10
      day to 5-day terlipressin treatment of bleeding esophageal varices.
AB  - BACKGROUND/AIMS: The aim of the study was to compare the efficacy and safety of 5
      day terlipressin treatment of bleeding esophageal varices to 10-day treatment
      period. METHODOLOGY: Of 25 patients with variceal bleeding, 15 were randomized to
      receive terlipressin for day 1-5 and placebo for day 6-10 (Group A), and 10 to
      receive terlipressin for day 1-10 (Group B). RESULTS: The bleeding was stopped in
      24 patients (96%). Rebleeding till day 42 was observed in 9 (36%) patients (5 in
      group A, 4 in group B, ns). 2 patients died in group B (due to rebleeding till
      day 5) and one in group A (rebleeding between day 5-10). Transfusion needs were
      lower in group B (2.7 +/- 2.6TU compared to 4.13 +/- 5.8 TU in group A, ns).
      Serious AE leading to treatment discontinuation were observed in 1 patient in
      group A (peripheral ischemia) and none in B, non-significant AE in 3 patients in
      group A (hypertension), and in 3 in group B (hypertension, hyponatremia,
      epiparoxysm). CONCLUSIONS: Prolonged treatment with terlipressin did not prove
      significant decrease of mortality or bleeding recurrence; lower rebleeding rate
      after day 5 and tendency towards lower transfusion requirements were observed.
      Prolonged treatment had no influence on AE rate.

PMID- 19579607
TI  - Feasibility of needle puncture measurement of variceal pressure in patients
      undergoing endoscopic variceal ligation.
AB  - BACKGROUND/AIMS: Concerning needle withdrawal bleeding, measurement of esophageal
      variceal pressures (VP) by direct needle puncture is indicated only when
      sclerotherapy is simultaneously performed. A prospective study was conducted to
      assess the feasibility of needle measurements of VP during endoscopic variceal
      ligation (EVL). METHODOLOGY: Liver cirrhotic patients who were consecutively
      referred for primary or secondary prevention of esophageal variceal bleeding
      between February 2003 and April 2005 were included in this study. Group A (n=47)
      received EVL immediately after needle puncture measurement of VP. Patients who
      received EVL only were included as controls (Group B, n=47). Arterial blood
      pressure (ABP), heart rate (HR), arterial oxygenation (SaO2) and morbidity were
      evaluated. RESULTS: The ABP was increased four hours after EVL in both groups,
      but there was no difference between the groups. There was a transient increase in
      HR and a decrease in SaO2 during endoscopy in both groups, but no difference of
      correspondent time points between the two groups. There was no difference in the
      bleeding rate between the two groups (9/47 vs. 10/47) CONCLUSION: Needle puncture
      measurement of VP is a feasible and safe method for use with EVL.

PMID- 19579606
TI  - Esophageal cancer resection associated with a right aortic arch after descending
      aortic graft replacement.
AB  - Right aortic arch is a rare abnormality. Esophageal cancer associated with a
      vascular ring is even more rare. We describe a patient with right aortic arch who
      had previously undergone a graft replacement of descending aorta for aneurysmal
      rupture followed by subsequent surgery for advanced esophageal cancer.
      Preoperative three-dimensional computed tomography revealed mirror image
      branching type right aortic arch and Kommerell's diverticulum of the descending
      aorta. The patient underwent total esophagectomy with laryngopharyngectomy and
      regional lymphadenectomy via a left thoracotomy. A permanent tracheal fistula was
      constructed. Postoperative chemo-radiotherapy was applied. The patient was
      discharged from hospital and is doing well. Early division of the ligamentum
      arteriosum with careful management of the aortic diverticulum led to release of
      the esophagus from the vascular ring that rendered the following procedures safe
      and afforded a good operative view.

PMID- 19579608
TI  - Response of atypical symptoms of GERD to antireflux surgery.
AB  - BACKGROUND/AIMS: The results of laparoscopic Nissen's fundoplication (LNF) were
      compared in patients having typical and atypical symptoms of Gastroesophageal
      reflux disease (GERD). Atypical symptoms include asthma, chronic cough, non
      cardiac chest pain, and ear, nose, and throat symptoms. The effectiveness of
      antireflux surgery in relief of these symptoms is uncertain. METHODOLOGY: 100
      patients with GERD underwent laparoscopic Nissen's fundoplication in El-Mansoura
      Gastro-enterology center between January, 2002 and March, 2004. Patients were
      classified according to preoperative symptoms into 3 groups; group 1 (71 cases
      with severe typical and minimal atypical symptoms), group 2 (18 cases with severe
      typical and severe atypical symptoms) and group 3 (11 cases with minimal typical
      and severe atypical symptoms). Patients were reassessed within a mean period of
      24 +/- 12 months after surgery. RESULTS: Duration of illness was nearly similar
      in the three groups (3.2 +/- 2.7:3.3 +/- 2.9:3.7 +/- 3.2 years). In group 1,
      typical symptoms improved in 66 (92.9%) cases and resolved in 63 (88.7%). In
      group 2, typical symptoms improved in 17 (94.4%) and resolved in 16 (88.9%),
      whereas atypical symptoms improved in 15 (83.3%) and resolved in 10 (55.6%). In
      group 3, atypical symptoms improved in 9 (81.8%) and resolved in 5 (45.5%).
      Endoscopic, radiologic, esophageal motility and pH metry studies were nearly
      similar in the 3 groups. CONCLUSIONS: Antireflux surgery improves atypical
      symptoms of GERD, but symptom resolution occurs in less than half of cases.

PMID- 19579609
TI  - Stent placement for portal venous stenosis following major abdominal surgery.
AB  - BACKGROUND/AIMS: This study was retrospectively undertaken to evaluate clinical
      utility of portal venous stent placement in the treatment of portal venous
      stenosis after major abdominal surgery combined with portal reconstruction.
      METHODOLOGY: Portal venous stent placement was done in 4 consecutive patients
      with anastomotic portal venous stenosis following major abdominal surgery
      combined with portal reconstruction. Liver dysfunction developed in all patients
      and consciousness loss in one patient, 1-55 days (mean, 19 days) after surgical
      intervention. Portal venous blood flow was not recognized by Doppler
      ultrasonographic studies in all patients. Expandable metallic stents were placed
      in the portal vein by percutaneous transhepatic approach in 2 patients and by
      transiliac approach in the other 2 patients. RESULTS: Stents were successfully
      placed across the anastomotic stenosis in all patients. Portal venous blood flow
      restored immediately after stent placement and liver dysfunction and
      consciousness loss resolved. Portal venous blood flow was maintained during the
      follow-up period ranging from 99 days to 765 days (mean, 438 days) in all
      patients. CONCLUSIONS: Portal venous stent placement is a useful therapeutic
      option for the treatment of anastomotic stenosis of portal vein following major
      abdominal surgery combined with portal reconstruction.

PMID- 19579610
TI  - COMT gene Val158Met polymorphism influences the severity of intestinal metaplasia
      in H. pylori infected older subjects.
AB  - BACKGROUND/AIMS: A complex interaction of host genetic and environmental factors
      may be relevant in the development of Helocobacter pylori (H. pylori) related
      gastroduodenal diseases. Catechol-O-methyltransferase (COMT) is expressed
      catalyzes the methylation of various endobiotic and xenobiotic substances and
      thus might protect DNA from oxidative damage. We aimed to clarify the effect of
      COMT functional polymorphism on the severity of histological gastritis in a
      Japanese population. METHODOLOGY: 203 subjects were included in this study.
      Restriction fragment length polymorphism analysis was performed for polymorphisms
      at codon 158 in the COMT gene. Gastritis scores of antral gastric mucosa were
      assessed according to the updated Sydney system. RESULTS: COMT genotype
      distribution in the study subjects was 158Val/Val (51.2%), 84Val/Met (41.4%), and
      15Met/Met (7.4%). It was within the Hardy-Weinberg equilibrium (p = 0.73). In
      over all subjects, the degree of intestinal metaplasia tended to be lower among
      158Met/Met when compared to Val/Val (Val/Val vs. Met/Met; 0.59 +/- 0.93 vs. 0.13
      +/- 0.52, p = 0.052). Among H. pylori infected subjects, the degree of intestinal
      metaplasia was significantly lower among 158Met carriers in 50 years or older age
      (Val/Val vs. Met carriers; 1.20 +/- 1.06 vs. 0.75 +/- 1.08, p = 0.0436). No
      significant association was found between COMT genotypes and the degree of
      gastritis in different gender CONCLUSION: Our data suggest that COMT gene 158Met
      polymorphism is associate with a reduced risk of developing more severe
      intestinal metaplasia in H. pylori infected older subjects.

PMID- 19579611
TI  - Clinical outcomes and advantages of laparoscopic surgery for primary Crohn's
      disease: are they significant?
AB  - BACKGROUND/AIMS: The clinical outcomes and advantages of laparoscopic surgery for
      Crohn's disease have not yet been recognized in general. The aim of this study
      was to critically assess the clinical outcomes, safety, cosmesis, quality of life
      (QOL) and feasibility of laparoscopic surgery for primary Crohn's disease.
      METHODOLOGY: The study subjects consisted of 48 patients who had primary surgical
      treatment for Crohn's disease, 28 through conventional laparotomy and 20 in whom
      surgery was laparoscopically assisted. The short-term and long-term outcomes,
      cosmesis, and postoperative QOL were evaluated in both groups. RESULTS: There
      were no statistically significant differences in the patient characteristics
      between the two groups. In the laparoscopic group, non-resected procedures were
      significantly more frequent (p < 0.05), blood loss was less (p < 0.05), oral
      intake was started earlier (p < 0.05) and the length of the skin incision was
      shorter (P < 0.01). The C-reactive protein values and leukocyte counts were not
      significantly different in the two groups. The cosmetic results were very
      satisfactory in 11 patients (64.7%). There were no severe complications and no
      increase of the recurrence rate for laparoscopic surgery. Moreover, there was no
      definite clinical disadvantage and no prolonged operating time in the
      laparoscopic procedures. CONCLUSIONS: Laparoscopic surgery for primary Crohn's
      disease is safe and feasible in selected patients without severe adhesion,
      fistula or abscess, and was associated with better cosmesis than conventional
      open surgery. Therefore, laparoscopic procedures should be considered as the
      preferred operative approach for a primary bowel resection.

PMID- 19579612
TI  - Allele frequency of thiopurine methyltransferase and inosine triphosphate
      pyrophosphatase gene polymorphisms in Korean patients with inflammatory bowel
      diseases.
AB  - BACKGROUND/AIMS: Adverse reactions to thiopurines may be predisposed by
      thiopurine methyltransferase (TPMT) or inosine triphosphate pyrophosphatase
      (ITPA) gene mutations. METHODOLOGY: We examined the frequencies of TPMT and ITPA
      gene polymorphisms in 812 Korean patients with inflammatory bowel diseases using
      denaturing high performance liquid chromatography and direct sequencing. RESULTS:
      The allele frequencies of TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C were 0, 0, 0, and
      0.010 (17/1624), respectively. For the ITPA polymorphism, 173 subjects were
      heterozygous and 5 were homozygous for the 94C>A missense mutation (allele
      frequency of A, 0.113). Moreover, the 87T>C, IVS2+21A>C, and IVS2+53C>T
      polymorphisms were found in one patient each (1/1624), respectively. Of these,
      87T>C and IVS2+53C>T were novel single nucleotide polymorphisms of the ITPA gene
      whose clinical significance should be further evaluated. CONCLUSIONS: Our data
      describe TPMT and ITPA gene mutation patterns among Koreans and provide a basis
      for screening studies to identify patients at high risk for myelotoxicity from
      thiopurine drugs.

PMID- 19579613
TI  - Is less more? A prospective trial on one trocar appendectomy.
AB  - One trocar appendectomy is a combination of laparoscopic and open appendectomy.
      The advantage, along with improved cosmesis, is the possibility to introduce a
      dissection instrument through the optical trocar without an additional incision.
      In this prospective study the sense of one trocar appendectomy is evaluated in
      daily practise for a cohort of consecutive patients with suspected acute
      appendicitis. Twenty-two patients were enrolled. One-trocar appendectomy was
      successful in 13 patients. In 8 patients one extra 2, 5 or 10 millimetre trocar
      was necessary. In one patient a third trocar was necessary. Conversion to an open
      appendectomy through a grid iron incision was not necessary. The pathologist
      confirmed the diagnosis of acute appendicitis in all patients. The average
      operation time was 53 minutes. Complications included one wound abscess and one
      wound haematoma. In conclusion one trocar appendectomy is a good and safe
      technique in patients with the suspicion of acute appendicitis, provided that the
      operative team must be experienced in laparoscopic surgery and the constitution
      of the patient is suitable for this technique.

PMID- 19579614
TI  - Ultrasound assisted percutaneous endoscopic jejunostomy.
AB  - The percutaneous endoscopic gastrostomy (PEG) cannot be performed for the patient
      after total gastrectomy. We design the new procedure to make jejunostomy with
      using an ultrasonography and a regular PEG kit. We name the procedure Ultrasound
      assisted Percutaneous Endoscopic Jejunostomy (USPEJ). Three cases has been
      performed USPEJ. Operating time is 30 minutes, 45 minutes and 10 minutes
      respectively. All cases were performed without any troubles. We conclude that the
      USPEJ is a useful method for the patient with dysphagia who has the past-history
      of total gastrectomy.

PMID- 19579615
TI  - Detection of hepatitis C virus in platelets: evaluating its relationship to
      antiviral therapy outcome.
AB  - BACKGROUND/AIMS: Detection of HCV has been documented in extrahepatic sites such
      as platelets. However, its influence on antiviral therapy outcome is unknown. In
      this study, we investigated the relationship between the detection of HCV in
      platelets from a cohort of 48 chronically HCV-infected patients and response to
      antiviral therapy. METHODOLOGY: This study comprised of 19 males and 29 females,
      mean age 54.9 +/- 8.72 years, followed-up in Rio de Janeiro, Brazil, between
      August 2004 and October 2006. HCV-RNA was detected in serum and platelets (pre
      treatment, end-of-treatment and 24 weeks after completion of therapy) by reverse
      transcription-nested polymerase chain reaction. Patients with genotype 1 or 4
      were treated with peginterferon-alfa/ribavirin for 48 weeks, and patients with
      genotype 3 received interferon-alfa/ribavirin for 24 weeks. RESULTS: Baseline
      detection of HCV in platelets was found not to be related to therapy outcome.
      However, significant associations between detection rates of HCV in platelets and
      serum at the end-of-treatment (p = 0.0203), and 24 weeks after completion of
      therapy (p = 0.0016) were observed. Interestingly, HCV was detected in platelets
      from two patients with normal ALT who lost detectable serum HCV at the end-of
      treatment and, after 24 weeks of followup, relapsed virologically in serum.
      CONCLUSIONS: Our data suggest that patients with HCV persistence in platelets by
      the end-of-treatment appear to be at an increased risk of recurrent HCV
      infection.

PMID- 19579616
TI  - Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients
      with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recently, complementary alternative medicine is actively
      performed for cancer therapy. We investigated the effectiveness of supplementary
      food containing superfine dispersed lentinan (beta-1,3-glucan) in patients with
      unresectable or recurrent hepatocellular carcinoma in a multi-center study.
      METHODOLOGY: Peripheral blood was collected prior to the test food ingestion and
      was incubated with fluorescein-labeled lentinan. The rates of lentinan-binding
      CD14+ monocytes were determined by flow cytometry. Patient survival times were
      followed up for 3 years. RESULTS: Thirty-six patients were eligible among 40
      enrolled patients. Median survival time of eligible patients was 13.6 months (95%
      confidence interval, 8.7-18.9 months). Survival times of patients who ingested
      test food for a mean period of 47 weeks (range, 26 to 145 weeks) were
      significantly longer than that of patients who ingested for 7 to 12 weeks (p <
      0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual
      variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3
      months) of lentinan-high-binding group were significantly longer than those
      (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05).
      CONCLUSIONS: A superfine dispersed lentinan-containing supplementary food is
      effective for hepatocellular carcinoma patients' survival. Long-time ingestion is
      preferable. Assessment of lentinan-binding CD14+ monocytes is a promising
      prognostic predictor.

PMID- 19579617
TI  - Application of hemihepatic vascular occlusion with hanging maneuver in
      hepatectomy.
AB  - BACKGROUND/AIMS: To evaluate the hemihepatic vascular occlusion with hanging
      maneuver in hepatectomy. METHODOLOGY: Ninety-four cases of hepatectomy were
      analyzed retrospectively. All patients were randomized into 3 groups: Pringle
      maneuver was applied in Group 1 (n=40), hemihepatic inflow control was Group 2
      (n=30) and complete hemihepatic vascular occlusion with hanging maneuver was
      applied in Group 3 (n=24).The clamping period, operation time, bleeding volume,
      blood transfusion volume, postoperative recovery of liver function and
      postoperative complications were compared among three groups. RESULTS: The
      average times of clamping in Group 1 was 1.6 +/- 0.7, but only one clamping in
      Group 2 and 3. There were significant differences among three groups in bleeding
      volume as well. The postoperative serum ALT and total bilirubin (TBIL) in Group 2
      and 3 were significantly lower than those of Group 1.5 patients died of liver
      failure after operation in Group 1. But liver failure or morbidity wasn't
      happened in Group 2 and 3. The rates of biliary leakage in Group 1 and 2 were
      more than that of Group 3. The hospitalization duration of Group 1 was
      significantly longer than those of Group 2 and 3. CONCLUSION: Hemihepatic
      vascular occlusion with hanging maneuver, which can reduce bleeding volume and
      enhance the recovery of liver function, is safe and practicable, especially for
      patients with liver cirrhosis.

PMID- 19579618
TI  - Usefulness and limitation of laparoscopic assisted hepatic resections: a
      preliminary report.
AB  - BACKGROUND/AIMS: We preliminarily examined the characteristics of patients who
      underwent laparoscopic assisted hepatic resection (LAPH) to clarify its
      advantages and limitations of this procedure. METHODOLOGY: We examined the
      demographics, surgical records and outcome in 9 patients undergoing LAPH between
      2001 and 2007 by comparing results in 15 patients (control group) who did not
      undergo laparoscopy before 2000. RESULTS: By comparing the control group, patient
      demographics were not different. Four patients underwent left lateral
      sectionectomy and others underwent partial hepatectomy. One patient needed
      combined resection of abdominal wall and left lateral sector because of direct
      invasion from a liver tumor. There was no remarkable morbidity or mortality in
      all patients. Mean operation time in the LAPH group was significantly longer than
      that in the control group (356 +/- 68 vs. 276 +/- 59 minutes) (p = 0.015),
      particularly in patients undergoing partial resection. Blood loss was not
      different between groups. Days of use of pain reliever and hospital stay in the
      LAPH group was significantly shorter than that in the control group (p < 0.001).
      These tendencies were similar in each operative procedure. CONCLUSIONS: LAPH can
      be safely performed even in patients with chronic liver injury and recovery of
      patients from operation was faster than that by conventional hepatectomy.

PMID- 19579619
TI  - High sensitivity C-reactive protein in spontaneous bacterial peritonitis with
      nonneutrocytic ascites.
AB  - BACKGROUND/AIMS: Diagnosis of spontaneous bacterial peritonitis in cirrhotic
      ascites is based on a polymorphonuclear leukocyte count of ascitic fluid equal or
      greater than 250/mm3 in the presence of clinical signs. There is a small number
      of patients with positive ascitic fluid culture whose polymorphonuclear leukocyte
      count is less than 250/mm3. In this study, we assessed the diagnostic value of
      serum high sensitivity C-reactive protein in spontaneous bacterial peritonitis
      with nonneutrocytic ascites. METHODOLOGY: Patients with decompensated cirrhosis
      were enrolled in three groups. Group 1: Signs and symptoms of peritonitis plus a
      polymorphonuclear leukocyte count of ascitic fluid equal or greater than 250/mm3.
      Group 2: Signs and symptoms of peritonitis, but polymorphonuclear leukocyte count
      of ascitic fluid less than 250/mm3. Group 3: No signs and symptoms of peritonitis
      and polymorphonuclear leukocyte count of ascitic fluid less than 250/mm3.
      Ceftriaxone was started in Groups 1 and 2. Serum level of hsCRP was repeated
      after the 2nd day of the antibacterial treatment. RESULTS: Mean levels of serum
      hsCRP were 68.4 mg/dl, 68.3 mg/dl and 6.5 mg/dl in Groups 1, 2 and 3
      respectively. Those levels were significantly higher in Groups 1 and 2 compared
      to Group 3 (p < 0.0001). After the 2nd day of ceftriaxone, serum hsCRP decreased
      to a mean level of 9.0 mg/dl in Group 1 and to 9.1 mg/dl in Group 2. CONCLUSION:
      These findings indicate that elevated hsCRP levels may discriminate patients with
      and without spontaneous bacterial peritonitis even in the presence of
      nonneutrocytic ascites, and may have utility in the assessment of treatment
      response.

PMID- 19579621
TI  - Liver function under interferon/ribavirin therapy of chronic hepatitis C.
AB  - BACKGROUND: Quantitative testing of liver function (QTLF) is one way to show the
      efficacy of antiviral treatment of Hepatitis C. Data on liver function in
      patients with chronic Hepatitis C during antiviral therapy are lacking. We
      therefore investigated if and to what extent antiviral therapy influenced
      quantitative testing of liver function (QTLF). METHODOLOGY: One hundrend seven
      patients with chronic Hepatitis C (genotype 1) were treated with pegylated
      interferon 2alpha/ribavirin for 48 weeks. Quantitative testing of liver function,
      including aminopyrine breath test (ABT), galactose elimination capacity (GEC),
      sorbitol clearance (SCl) and indocyanine green clearance (ICG) was performed
      before and 12 weeks after initiation of antiviral therapy. QTLF was repeated at
      the end of the therapy (week 48) and 6 months after therapy. RESULTS: After 3
      months of treatment, 97 patients showed normal transaminases and were negative
      for HCV-RNA. ABT and GEC as parameters of microsomal and cytosolic liver function
      were reduced in all patients before therapy initiation and returned to normal
      values in the therapy responders after 3 months. Parameters of liver perfusion
      (SCl and ICG) require one year of treatment before returning to normal levels. In
      non-responders, QTLF did not change during therapy, in relapsers, QTLF results
      deteriorated after ending the therapy. CONCLUSION: All liver tests return to
      normal within one year after eradication of the Hepatitis C virus. Parameters
      measuring the liver plasma flow (SCI and ICG) require more time to become normal,
      most likely due to tissue remodelling processes.

PMID- 19579620
TI  - Artificial liver support system in acute liver failure patients waiting liver
      transplantation.
AB  - BACKGROUND/AIMS: To assess the efficacy of the Molecular Adsorbent Recirculating
      System MARS (GAMBRO LUNDIA AB, Europe) in patients with acute liver failure
      waiting for liver transplantation. METHODOLOGY: Case-control study in a medical
      surgical ICU of a referral hospital. Patients admitted to ICU with severe acute
      liver failure of any etiology were included. Conventional treatment was applied
      in all cases according to patient's clinical condition. Patients were treated
      with MARS after the implementation of this therapy in the ICU. Patients without
      this treatment were the control group. RESULTS: Were included 45 patients
      (control group: 26, MARS group: 19). Comparison between groups showed only
      differences in plasma bilirrubin levels in the first 24 hours. ICU mortality was
      52.63% in the treatment group and 42.3% in the control group (p = 0.49). In the
      control group 17 patients (65.4%) received a liver transplant and 11 (57.9%) in
      the MARS group. ICU mortality was lower for transplanted patients in the study
      group (27.27% vs. 87.5%) (p = 0.019). Kaplan-Meier survival curves indicate that
      MARS-treated patients before liver transplantation had better survival.
      CONCLUSIONS: Combination therapy with MARS and liver transplantation seems to be
      the more effective therapeutic option for patients with severe ALF.

PMID- 19579622
TI  - Rate of chronicity and time of disappearance of HBsAg following acute hepatitis
      B.
AB  - BACKGROUND/AIMS: Chronic hepatitis B is associated with significantly increased
      risk of developing cirrhosis, and hepatocellular carcinoma. It's, therefore,
      important to understand the incidence and risk factors associated with chronicity
      following acute hepatitis B. METHODOLOGY: Among 863 acute hepatitis patients
      admitted consecutively to the hospital, 320 with serum immunoglobulin M antibody
      to hepatitis B core antigen were classified as acute hepatitis B. Of these
      patients, serum samples were collected 3 and 6 months after clinical onset.
      RESULTS: Complete follow-up was achieved in 240 patients and 11 (4.6%) became
      chronic carriers. Only alcohol addiction other than epidemiological, clinical or
      biochemical parameters was found to be significantly associated with chronic
      evaluation. In serum samples collected from 205 of 240 patients 3 months after
      the onset of infection, hepatitis B surface antigen clearance was observed in 181
      (88.3%). Number of patients increased to 194 (94.6%) at the end of 6 month and
      both of these rates were found to be highly significant. CONCLUSIONS: There is
      still no certain way of predicting the outcome of acute hepatitis B whether a
      newly infected patient will resolve the illness or not. Alcohol addiction seems
      to have an impact on the chronicity but additional research is needed.

PMID- 19579623
TI  - Erythropoietin strongly protects the liver from ischemia-reperfusion injury in a
      pig model.
AB  - BACKGROUND/AIMS: We investigated, for the first time, the protective effect of
      erythropoietin (EPO) against liver ischemia-reperfusion (I-R) injury in a pig
      model. METHODOLOGY: Partial hepatic ischemia was maintained for 60 min in a pig.
      Pigs were allocated to 4 groups (n=5 each): (1) Control group with I-R injury
      (Vehicle); (2) EPO group with I-R injury, given three injections of EPO at 5000
      IU/kg (EPO5000x3); (3) EPO group with I-R injury, given a single injection of EPO
      at 5000 IU/kg (EPO5000x1); and (4) EPO group with I-R injury, given three
      injections of EPO at 500 IU/kg (EPO500x3). Liver function tests (AST, ALT, LDH),
      and TUNEL assay were performed. RESULTS: Three hours after I-R injury, AST levels
      in the Vehicle, EPO5000x3, EPO5000x1, and EPO500 x3 groups were 1494.2 +/- 711.3
      U/L, 307.3 +/- 127.6 UL, 296.5 +/- 9.2 U/L, and 474.6 +/- 242.0 UL, respectively
      (one-factor ANOVA, p = 0.020). At 3h the ALT and LDH levels in the Vehicle group
      were significantly higher than those in the EPO5000x3 and EPO5000x1 groups.
      Apoptotic indices in the Vehicle, EPO500x3, EPO5000x1, and EPO500x3 groups 3 h
      after I-R injury were 2.40 +/- 0.93, 1.36 +/- 0.12, 1.11 +/- 0.17, and 1.51 +/-
      0.33, respectively. The apoptotic indices of the EPO5000x1 and EPO500x3 groups
      were significantly lower than that of the Vehicle group. CONCLUSIONS: EPO
      treatment significantly ameliorated liver I-R injury in this pig model. The
      protective effect was exerted by the inhibition of apoptosis. These results will
      open the door for the clinical application of EPO in liver surgery.

PMID- 19579624
TI  - Radiation therapy for lymph node metastases from hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recent improvements in the prognosis of patients with
      hepatocellular carcinoma (HCC) render the discovery and treatment of lymph node
      (LN) metastasis increasingly important. We retrospectively evaluated the
      treatment outcomes of radiation therapy (RT) for LN metastases from HCC.
      METHODOLOGY: Twenty-three patients with LN metastases from HCC underwent RT. A
      daily dose of 1.8-4 Gy was administered to deliver a total dose of 28-56 Gy,
      which was a biologic effective dose (BED) of 36-67.2 Gy10 (median 58.5 Gy10) with
      an alpha/beta ratio of 10. We evaluated predictive factors for local control and
      survival. RESULTS: A complete response and partial response were recorded for 5
      and 14 patients, respectively. The response rate was 83%; it was significantly
      higher in patients who had received > or =58 Gy10 rather than <58 Gy10 (P =
      0.014). The median survival time was 19 months. Univariate analysis revealed that
      the Child-Pugh's classification, status of the liver tumor, and LN metastasis
      site were significant factors for survival. Multivariate analysis showed that the
      status of the liver tumor was the only independent predictor of survival.
      CONCLUSIONS: RT is effective for the local control of LN metastases from HCC
      without a confirmed survival effect. RT doses greater than 58 Gy10 are required
      for a better local response.

PMID- 19579625
TI  - Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via
      death ligands.
AB  - BACKGROUND/AIMS: Phosphatidylcholine reduces chemically-induced
      hepatocarcinogenesis in rats and the growth of hepatic cancer cells. We planned
      to determine whether apoptosis pathways via death ligands were induced by
      phosphatidylcholine. METHODOLOGY: Growth inhibition of hepatic cancer cell lines
      (HepG2, Hep3B, Alexander, and HuH-7) was examined by MTT assay. On apoptosis
      induction, flow cytometry analyses were performed after Fas or TNF-alpha ligand
      stimulation followed by phosphatidylcholine. Expressions of caspase-8, -3 and
      PARP after phosphatidylcholine stimulation were examined by immunoblotting. TUNEL
      staining was also performed after phosphatidylcholine stimulation. RESULTS: MTT
      assays showed growth inhibitions by phosphatidylcholine dose-dependently. Ratios
      of sub-G1 phase cell population by FACScan significantly increased on 48h
      phosphatidylcholine stimulation in comparison to the control group (p < 0.05).
      Fas or TNF-alpha ligand followed by phosphatidylcholine stimulation significantly
      increased apoptotic cells more than by phosphatidylcholine alone (p < 0.05).
      Enhanced appearances of cleaved caspase-8, -3 and fragmented PARP were shown on
      immunoblotting and apoptotic cells on TUNEL staining after phosphatidylcholine
      stimulation. Phosphatidylcholine was assumed to reduce hepatic carcinogenesis by
      apoptosis induction via the death ligands (Fas and/or TNF-alpha) pathway followed
      by caspase-8 and -3 inductions. CONCLUSIONS: Phosphatidylcholine intake may well
      inhibit carcinogenesis in patients at high risk for hepatocellular carcinoma by
      apoptosis induction.

PMID- 19579626
TI  - Comparison of biochemical safety between PEG-IFN alpha-2a and PEG-IFN alpha-2b.
AB  - BACKGROUND/AIMS: Although the efficacy and safety of pegylated-interferon (PEG
      IFN) alpha-2a and PEG-IFN alpha-2b have been comparatively studied, there are few
      study results available in which the two PEG-IFN products were strictly compared.
      To compare the effects of two PEG-IFN products on blood cell profile.
      METHODOLOGY: The time-course change in blood cell counts was compared between
      chronic hepatitis C patients with genotype 1b receiving PEG-IFN alpha
      2a/ribavirin and PEG-IFN alpha-2b/ribavirin combination therapy. The comparison
      was made after matching patients from the two groups based on ribavirin apparent
      clearance (CL/F), a surrogate marker of the steady state blood ribavirin level,
      in order to eliminate the effect of ribavirin. Fifteen pairs of matched patients
      were selected. RESULTS: The time-course change in hemoglobin did not differ
      significantly between the two groups. However, significantly greater reductions
      in both neutrophil and platelet counts were observed with PEG-IFN alpha-2a
      compared to PEG-IFN alpha-2b. A slightly longer period was required with PEG-IFN
      alpha-2a than with PEG-IFN alpha-2b for a reduction in neutrophil or platelet
      count large enough to necessitate dose reduction. CONCLUSIONS: Two types of PEG
      IFN products affected the blood cell profile in different manners. Long-term
      monitoring of laboratory test values is necessary with PEG-IFN alpha-2a.

PMID- 19579627
TI  - Selective periesophagogastric devascularization in portal hypertension: results
      of 56 patients.
AB  - BACKGROUND/AIMS: Surgery remains the most reliable treatment for bleeding
      esophageal varices. We propose a new modified procedure as selective
      periesophogastric devascularization (SPD), in which paracardial spontenous
      collaterals were preserved and only pericardial collaterals and perforating
      branches were disconnected. This study aimed to evaluate the results of SPD in
      variceal bleeding. METHODOLOGY: The results of 56 patients subjected to SPD for
      bleeding esophageal varices, were retrospectively reviewed. Etiology of portal
      hypertension was chronic HBV cirrhosis in 80.4% (45/56), alcoholic in 12.5%
      (7/56) and others 7.1% (4/56). Child-Pugh grading on admission was A: 78.6%
      (44/56), B: 14.3% (8/56), and C: 7.1% (4/56). Evaluation was made in terms of
      effectiveness in controlling the acute bleeding, postoperative morbidity and
      mortality, recurrent bleeding, encephalopathy and 3-year survival rate. RESULTS:
      Hemorrhage was controlled in all cases with no death rate. Portal vein thrombosis
      in 3.6% (2/56), and pleurorrhea in 8.9% (5/56) of cases. In-hospital morbidity
      was 12.5% (7/56). Complete eradication of varices was observed in 87.5% (49/56)
      patients. Recurrent variceal bleeding was noticed in 8.9% (5/56) of cases. No
      patient developed encephalopathy until one month postoperatively. 42 patients
      were followed up postoperatively for three years. The 3-year survival for
      patients with Child-Pugh A was 100% (32/32), B was 71.4% (5/7), and 33%(1/3) for
      C. CONCLUSIONS: SPD was safe and effective in control of bleeding varices in
      portal hypertension.

PMID- 19579628
TI  - Vascular transection using endovascular stapling in hepatic resection.
AB  - In anatomical resection of the liver, transection of the hepatic vein or
      Glisson's pedicle is necessary. We examined the surgical records and outcome of
      25 patients who underwent hepatectomy. An endovascular stapler with 35 and 60 mm
      staples was used for transection of the hepatic vein or Glisson's pedicle, and
      hepatic parenchyma including vessels. Surgery included also left lateral
      sectorectomy in 6 patients, right lateral sectorectomy in one, right hepatectomy
      in 12, left hepatectomy in two and trisegmentectomy in 4. Endovascular stapling
      was used for transection of hepatic veins (n=25) in all patients and Glisson's
      pedicle (n=8). No failure of firing occurred during cutting. Injury of an
      aberrant bile duct occurred in one patient, but none suffered bleeding or bile
      leakage from the transected parts. Vascular transection using vascular stapler
      could be performed safely and rapidly during anatomical hepatic resection.

PMID- 19579629
TI  - Influence of body mass index, cholesterol, triglycerides and steatosis on
      pegylated interferon alfa-2a and ribavirin treatment for recurrent hepatitis C in
      patients transplanted for HCV and alcoholic cirrhosis.
AB  - Up to today no work has evaluated yet the importance of parameters such Body Mass
      Index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis
      in the response to therapy with Pegylated Interferon Alfa-2a and Ribavirin in
      patients with recurrent hepatitis C (genotype 1). 30 consecutive prospectively
      followed patients diagnosed with recurrent HCV were considered candidates for
      antiviral therapy. Qualitative and quantitative detection of HCV-RNA was
      performed with the Cobas Amplicor Hepatitis C Virus Test, version 2.0 and the
      Cobas Amplicor HCV Monitor, version 2.0 (Roche Diagnostics, Branchburgh, NJ,
      U.S.A.). HCV genotyping was performed by sequencing of the 5 untraslated region
      (5' UTR) (Visible Genetics TruGene Hepatitis Assay, Toronto, Canada). The
      observed distribution of BMI, cholesterol, TGC and steatosis were confirmed to be
      normally distributed by the one-sample Kolmogorov-Smirnov Goodness of fit test
      procedure. Comparison of BMI, cholesterol, TGC and steatosis between non
      responders (NR), sustained virological responders (SVR) and sustained biochemical
      responders (SBR) groups were analyzed by ANOVA with a post hoc Bonferroni test
      and correlation between variables was tested by Pearson test. The multivariate
      analysis was performed to estimate the chance of response on basis of the above
      mentioned variables. In patients with abnormal results in at least two out of
      four considered variables the chance of no-response was 40 times higher than that
      of SBR and 96 times than that of SVR. We can conclude how the management of
      dismetabolism, diet and exercise therapy can improve BMI, liver histology and,
      therefore, the response to PEG-IFN Alfa-2a and Ribavirin.

PMID- 19579630
TI  - Right-sided posttraumatic diaphragmatic rupture and delayed hepatic hernia.
AB  - The early diagnosis of posttraumatic diaphragmatic lesions is often difficult
      which explains the 30 to 50% of non diagnosed cases. This is due to the lack of
      sensitivity and specificity of the radiographic exams. Missed diaphragmatic
      lesions results in herniation of abdominal contents into the chest and may be
      revealed many years from the time of the original trauma. Symptoms such as
      dyspnea and chronic abdominal complaints are often observed and life-threatening
      complications, such as visceral strangulation or perforation, contribute to the
      late morbidity and mortality of the missed injury. Liver herniation is rare and
      few cases are described in the literature. We report two cases of delayed
      discovery of the diaphragmatic injury resulting in liver herniation. In one case,
      there was also an involvement of the duodeno-pancreas. The diagnosis was made 3
      and 12 years after the original trauma, respectively, and respiratory
      embarrassment was the major presenting symptom. The surgical approach was
      different in the two patients; the first patient was managed by thoracotomy
      whereas the second patient was treated by laparotomy. The diaphragmatic defect
      was repaired and reinforced by a prosthetic mesh in the first case. It was closed
      only by suturing in the second patient. From these two cases, we reviewed the
      relevant literature and analysed the different approaches for diaphragmatic
      repair.

PMID- 19579631
TI  - Ante-situm liver resection in recurrent liver metastasis from colorectal cancer.
AB  - Surgical resection of liver metastases from colorectal cancer can offer long-term
      survival and cure in patients with metastatic colorectal cancer isolated to the
      liver. We present a case of a recurrent liver metastasis from rectal cancer,
      managed with ante-situm liver resection under total vascular exclusion and
      venovenous bypass with hypothermic perfusion. A 58-year-old man, who was
      diagnosed with liver metastasis from rectal cancer underwent a left lateral
      sectionectomy in January 2006. A recurrent lesion developed 1 year after the
      first hepatectomy. The tumor was 5 cm in size, locating at segments I, IV, and
      VIII. It was involved in the origin of middle hepatic vein and retro-hepatic vena
      cava. We performed ante-situm liver resection under total vascular exclusion and
      venovenous bypass with hypothermic perfusion. The patient remains well without
      recurrence for 12 months after the last operation. Ante-situm technique made it
      easy to approach and completely removes the recurrent lesion locating at hardly
      accessible site and having the incomplete removal risk by conventional liver
      resection. The authors also reconfirmed that repeat hepatectomy is valuable in
      recurrent colorectal liver metastases.

PMID- 19579632
TI  - Left hepatectomy for metastatic thrombosis of umbilical vein and left portal vein
      from renal cell carcinoma.
AB  - Renal cell carcinoma is an aggressive tumor which is often advanced at the time
      of diagnosis; its distant spread can take a lymphatic route or, more often, a
      vascular route (renal vein and inferior vena cava), but tumor thrombosis of left
      portal vein extending into the round ligament (the umbilical vein) coming from
      this tumor, to our knowledge, has never been described. We report the case of a
      metastatic thrombosis of left portal vein and of the umbilical vein from renal
      cell carcinoma, developed 13 years after nephrectomy, which was successfully
      treated with left hepatectomy. The experience with hepatectomy for metastatic
      renal cell carcinoma has been rarely reported. Nevertheless radical hepatectomy
      is considered to be the only opportunity for curative treatment for selected
      patients with metastatic renal cell carcinoma.

PMID- 19579633
TI  - Role of CT in detecting malignancy during follow-up of patients with branch-type
      IPMN of the pancreas.
AB  - BACKGROUND/AIMS: This retrospective study evaluated the suitability of computed
      tomography (CT) to detect malignancy while following patients with branch-type
      IPMN, most of which are benign and may be treated with observation alone.
      METHODOLOGY: Forty-two surgical specimens resected from patients with a diagnosis
      of branch-type IPMN were pathologically classified as benign (n=26), which
      included hyperplasia and adenoma, or malignant (n=16), including moderate
      dysplasia or adenocarcinoma. It was compared the differences in the sizes of the
      tumor and main pancreatic duct (MPD) and the presence of mural nodules on CT
      between the groups. RESULTS: In the malignant group, it was observed a larger
      tumor size (47.8 vs. 23.8 mm; p = 0.001) and increased dilation of the MPD (9.3
      vs. 5.0 mm; p = 0.001) than those seen in the benign group. The accuracy of CT
      diagnosis of mural nodules, however, was only 62%. Tumor diameter > or =40 mm or
      MPD diameter >10 mm predicted malignancy with a sensitivity and negative
      predictive value of 93.8% and 95.7%, respectively. CONCLUSIONS: Either tumor size
      or MPD dilation detected by CT could predict the majority of malignant branch
      type IPMNs. Increases in these morphological characteristics on CT images during
      the follow-up period would be an accurate method to predict a diagnosis of
      malignancy.

PMID- 19579634
TI  - Pancreatic fistula formation after pancreaticooduodenectomy; for prevention of
      this deep surgical site infection after pancreatic surgery.
AB  - BACKGROUND/AIMS: The operative mortality and morbidity associated with
      pancreatoduodenectomy (PD) has been decreasing, however, pancreatic fistula
      remains a major cause of a potentially fatal complication. The aim of this study
      was to identify risk factors, predictors and prevention for pancreatic fistula
      formation in a consecutive series of PD cases in a single institution.
      METHODOLOGY: The association between pancreatic fistula formation and various
      clinical parameters was investigated in 100 patients who underwent PD at Kochi
      Medical School from April 1999 through December 2007. RESULTS: The incidence of
      pancreatic fistula in these patients was 18%. Multivariate analysis identified 4
      independent parameters correlating with occurrence of pancreatic fistula: (1) no
      use with ultrasonically activated scalpel on the pancreatic transaction (odds
      ratio, 2.1; 95% confidence interval, 1.2-3.8; p = 0.001); (2) no performance with
      duct-to-mucosa anastomosis for pancreatico-enteric reconstruction (4.3; 1.1-16.1;
      p = 0.006); (3) not having early postoperative enteral nutrition through the
      jejunostomy catheter (2.3; 1.1-5.0; p = 0.007); and (4) serum amylase
      concentration greater than 194 U/L (1.7 times the normal upper limit) on the
      first postoperative day (2.0; 1.1-3.9; p = 0.019). CONCLUSION: The current study
      suggested that the reconstruction of duct-to-mucosa anastomosis for pancreatico
      jejunostomy by using the ultrasonically activated scalpel and the use of early
      postoperative enteral nutrition should be attempted as a means to reduce the
      incidence of pancreatic fistula after PD.

PMID- 19579635
TI  - Therapeutic efficacy of continuous arterial infusion of the protease inhibitor
      and the antibiotics and via celiac and superior mesenteric artery for severe
      acute pancreatitis--pilot study.
AB  - BACKGROUND/AIMS: Severe acute pancreatitis is poor prognosis. Continuous regional
      arterial infusion of protease inhibitors and antibiotics were developed in Japan.
      We evaluated whether arterial infusion both celiac artery and superior mesenteric
      artery for this disease would reduce mortality. METHODOLOGY: Seventeen patients
      were treated arterial infusion of protease inhibitor and antibiotics via both
      celiac artery and superior mesenteric artery. Changes of Acute Physiology and
      Chronic Health Evaluation II score and mortality were evaluated. RESULTS:
      Arterial infusion via two routes reduced the mortality rate and improved Acute
      Physiology and Chronic Health Evaluation II score. The overall mortality rate was
      11.8%. The mortality rate in patients in whom were treated within 3days after the
      onset was significantly lower than that in patients in whom were treated without
      3days after the onset. CONCLUSIONS: Arterial infusion via superior mesenteric
      artery might prevent both bacterial translocation and non-occlusive mesenteric
      ischemia. Continuous arterial infusion both celiac artery and superior mesenteric
      artery might be effective for reducing mortality and preventing the development
      of pancreatitis, especially when initiated within 3 days after the onset. Further
      prospective randomized studies using a larger number of patients are required.

PMID- 19579636
TI  - Pre-operative patient selection of pancreatic cancer patients by multi-detector
      row CT.
AB  - BACKGROUND/AIMS: Accurate pre-operative staging in patients with pancreatic
      cancer is crucial for avoiding unnecessary laparotomy and for selecting patients
      accurately for curative resection. In this study, tumor resectability and
      residual tumor grading in patients evaluated by MD-CT (Multi-detector row CT) or
      by SD-CT (single-detector CT) were compared to determine whether more accurate
      imaging has a significant clinical impact on patient selection and surgical
      outcomes. METHODOLOGY: One hundred-fifty consecutive patients with pancreatic
      cancer evaluated from January 2000 to April 2005 were included in this
      retrospective study. Seventy pancreatic cancer patients underwent pre-operative
      evaluation using SD-CT and angiography (5-7 mm slice thickness, 1st period 2000
      2002), and 80 patients underwent MD-CT (1.25 mm slice thickness, 2nd period 2002
      2005). RESULTS: The introduction of MD-CT had a significant impact on the
      selection of suitable patients, this group showing a lower frequency of surgical
      intervention in cases of incurable disease (p = 0.0383). Pre-operative evaluation
      using MD-CT in the resected cases also provided a higher percentage of accurate
      R0/R1 grading relative to SD-CT evaluations (p = 0.0164). CONCLUSION: MD-CT
      imaging has a significant impact on preventing unnecessary exploratory surgery
      and on the selection of appropriate pancreatic cancer patients for surgical
      resection.

PMID- 19579637
TI  - Intraoperative pancreatography using an endoscopic naso-pancreatic drainage tube
      for the prevention of pancreatic fistula after local pancreatic resection.
AB  - BACKGROUND/AIMS: Local pancreatic resections can avoid the unnecessary resection
      of the normal pancreatic parenchyma in comparison with standard pancreatic
      resection. However, the incidence of pancreatic fistula after local pancreatic
      resection is high, and still responsible for most morbidity and mortality.
      METHODOLOGY: We reviewed 6 patients who underwent intraoperative pancreatography
      using an endoscopic naso-pancreatic drainage (ENPD) tube during local pancreatic
      resection for the prevention of postoperative pancreatic fistula. RESULTS: One
      patient had injury to the main pancreatic duct during surgery, and transient
      pancreatic fistula of grade B occurred. In this patient, ENPD tube was left in
      place for the management the pancreatic fistula, resulted in a favorable outcome.
      Other 5 patients showed no postoperative complications including pancreatic
      fistula. CONCLUSIONS: Intraoperative pancreatography using ENPD tube is a simple
      technique and useful for the prevention of pancreatic fistula after local
      pancreatic resection.

PMID- 19579638
TI  - Portal and splenic venous thrombosis after splenectomy in patients with
      hypersplenism.
AB  - BACKGROUND/AIMS: Portal and splenic venous thrombosis (PSVT) is not a rare
      complication of splenectomy. We report a retrospective study of PSVT after
      splenectomy in patients with liver cirrhosis and clarify the risk factors and
      discuss the necessity of preventive pharmacotherapy. METHODOLOGY: Potential
      subjects comprised 27 patients who underwent splenectomy (including laparoscopic
      splenectomy) at our hospital between January 2003 and December 2005 for
      hypersplenism due to liver cirrhosis. Perioperative data were assessed for 17
      patients who did not have portal tumor thrombus and followed-up regularly.
      RESULTS: PSVT occurred in 5 of the 17 patients (29%), none of them were
      symptomatic throughout follow-up. PSVT disappeared spontaneously in 2 of the 5
      patients (40%) without any treatment. Patients with PSVT showed significant
      differences in comparison with patients without PSVT in age, preoperative
      platelet count, intraoperative bleeding,splenic weight and platelet-associated
      immunoglobulin G (PAIgG), CONCLUSIONS: PSVT occured at a high rate in patients
      after splenectomy, but at a lower than in patients with hematopathies. According
      to our results, thrombolytic agent may be required only when patients show
      symptoms of PSVT. Preoperative serum PAIgG level may represent worthwhile markers
      for predicting PSVT.

PMID- 19579639
TI  - Gastric phenotypic expression and histogenesis of metachronous gastric cancers
      endoscopically resected.
AB  - BACKGROUND/AIMS: Endoscopic Resection (ER) has been performed for early gastric
      cancers, and metachronous gastric cancers (MGCs) were occasionally observed. Most
      MGCs were classified histologically as the differentiated type. However, there
      have been no data on the gastric and intestinal phenotypic classification of
      MGCs. In our previous study, Hp-infection in MG may trigger intestinalization of
      gastric cancers. We therefore speculate the phenotype shift in MGC lesions under
      Hp-chronic-infection. METHODOLOGY: We examined the 17 MGC lesions phenotypically
      and histologically by using several gastric and intestinal epithelial cell
      markers, MUC5AC, MUC6, MUC2 and villin. RESULTS: Most lesions (16/17) exhibited
      the differentiated type. In 8 first cancers, the lesions were divided
      phenotypically into 2 G, 4 GI, 1 I, and 1 N types. In 9 second/third cancers, the
      lesions were divided phenotypically into 3 G, 1 GI, 4 I, and 1 N types. The first
      lesions (6/8) had more gastric phenotypic expression compared with the
      second/third ones (4/9) in the MGCs, although there was no significant difference
      between two groups (P = 0.28). CONCLUSION: Our present data suggest the
      possibility that the cancer retaining G type is detected endoscopically earlier
      than that obtaining the intestinal phenotypic expression by the phenotypic shift,
      which may partially explain the MGC occurrence.

PMID- 19579640
TI  - Lentinan with S-1 and paclitaxel for gastric cancer chemotherapy improve patient
      quality of life.
AB  - BACKGROUND/AIMS: Lentinan (LNT), a purified beta-glucan, is a biological and
      immunological modifier and has been used as an anticancer drug in combination
      with 5-fluorouracil for gastric cancer in Japan. In this prospective randomized
      study, we evaluated the effects of LNT combination with regard to quality of life
      (QOL) and LNT binding ratio in monocytes. METHODOLOGY: Twenty patients were
      evaluated for 12 weeks. One cycle was 3 weeks and S-1 (day1-14) and Paclitaxel
      (days1 and 8) were administered. LNT was used once a week (days 1, 8 and 15) and
      it was used for all 12 weeks in the LNT 12-wk group and only for the last 6 weeks
      in the LNT 6-wk group. QOL was evaluated weekly by QOL-ACD, and binding of LNT to
      monocytes was measured by flow cytometry. RESULTS: There were individual
      variations in the binding ratio of LNT to monocytes from 0.16% to 11.95%.
      Toxicity with chemotherapy was not improved in the LNT 12-wk group, however, the
      total QOL score was significantly elevated in the LNT 12-wk group (p = 0.018) but
      not in the LNT 6-wk group. CONCLUSION: LNT combination from the beginning of the
      chemotherapy may be an important factor for the improvement of patient QOL.

PMID- 19579641
TI  - Early effects of intravenous administrations of lansoprazole and famotidine on
      intragastric pH.
AB  - BACKGROUND/AIMS: The ideal medication for treatment of acid related diseases
      should have a rapid onset of action to promote hemostasis. The aim of our study
      was to investigate the inhibitory effects on gastric acid secretion after single
      intravenous administrations of lansoprazole 30 mg and famotidine 20 mg.
      METHODOLOGY: Twelve Helicobacter pylori-negative male subjects participated in
      this randomized, two-way crossover study. Intragastric pH was monitored
      continuously for 4 hours after single intravenous administration of lansoprazole
      30 mg or famotidine 20 mg. RESULTS: The average pH during the 4-hour period after
      administration of famotidine was higher than after lansoprazole (median: 5.15
      versus 3.55, respectively; p = 0.0376). During the 4-hour study period,
      famotidine 20 mg provided a longer duration of pH > 3, 3.5, 4, 5, 6 and 7,
      compared to lansoprazole 30 mg (median: 73.6% versus 57.0%; p = 0.0414, 66.8%
      versus 47.8%; p = 0.0281, 60.8% versus 38.8%; p = 0.0150, 55.7% versus 29.7%; p =
      0.0281, 45.0% versus 23.1%; p = 0.0414 and 23.9% versus 3.65%; p = 0.0076).
      CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, an
      intravenous dose of famotidine 20 mg more rapidly increases intragastric pH than
      lansoprazole 30 mg.

PMID- 19579642
TI  - Chloroxoquinoline in combination with epirubicin, cisplatin and 5-fluorouracil in
      metastatic gastric cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and
      tolerability of combination chemotherapy with epirubicin, cisplatin, 5
      fluorouracil (ECF regimen), and Chloroxoquinoline in patients with metastatic
      gastric cancer. METHODOLOGY: Twenty-two patients with histologically confirmed
      metastatic gastric adenocarcinoma were treated with a combination of epirubicin
      50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), 5-fluorouracil 500 mg/m2 (days 1 to
      5), and Chloroxoquinoline 400 mg (days 1 to 21), with the cycle repeated every
      three weeks. RESULTS: Twenty patients were evaluable for response. One case of
      (5%) complete response, seven of (35%) partial response, nine (45%) of stable
      disease, and three (15%) of progressive disease were observed, giving an overall
      treatment response rate of 40%. Median survival time was 9.4 months, median
      progression-free survival was 6.1 months, and the 1-year survival rate was 25%.
      Both hematologic and non-hemotologic toxicities were well tolerated and no
      treatment-related deaths occurred. In patients who received Chloroxoquinoline
      maintenance monotherapy after six cycles of the combination regimen, progression
      free survival was nine months. CONCLUSION: The combination regimen demonstrated
      comparable efficacy and acceptable safety profiles in patients with metastatic
      gastric cancer. Chloroxoquinoline maintenance monotherapy has a tendency to
      increase progression-free survival.

PMID- 19579643
TI  - Significance of sucrose permeability test in detecting early gastric cancer and
      changes of permeability after endoscopic mucosal resection.
AB  - BACKGROUND/AIMS: To evaluate the diagnostic value of sucrose permeability test
      (SPT) with special reference to early gastric cancer (EGC), and to assess the
      changes of urinary sucrose level after treatment of gastric damage: gastric ulcer
      (GU) or EGC. METHODOLOGY: Ninety subjects were included in this study, that is;
      18 patients with GU, 25 EGC, 17 advance gastric cancer (AGC), and 30 healthy
      volunteers (HV). SPT was conducted before treatment in all the subjects, and in 6
      patients each with GU and EGC after treatment- proton pump inhibitor for GU and
      endoscopic mucosal resection for EGC. Diagnostic values were calculated based on
      cut-off values estimated from the ROC curves. RESULTS: The mean amount of sucrose
      excreted into urine in HV, GU, EGC, and AGC was 50.8 +/- 28.0 mg, 225.9 +/- 201.1
      mg, 170.2 +/- 86.4 mg, and 426.2 +/- 155.0 mg, respectively, showing significant
      differences between HV and gastric disease groups (p < 0.01). The sensitivity for
      detecting GU, EGC, and AGC was 94.4%, 88.0%, and 100%, respectively. Sucrose
      excretion in GU and EGC was significantly decreased after treatment (262.4 +/-
      121.2 to 80.6 +/- 42.1, and 246.0 +/- 136.9 to 139.1 +/- 69.2, p < 0.05 and p <
      0.001, respectively). CONCLUSIONS: SPT was considered useful to detect not only
      GU or AGC but also EGC with a high sensitivity. A significant decrease of sucrose
      excretion was observed after treatment in EGC.

PMID- 19579644
TI  - Vertical stomach reconstruction with pancreaticogastrostomy after modified
      subtotal-stomach-preserving pancreaticoduodenectomy for preventing delayed
      gastric emptying.
AB  - Pylorus-preserving pancreaticoduodenectomy (PPPD) yields better results in terms
      of operative mortality and morbidity and postoperative nutritional state than
      those obtained after Whipple procedure. However, delayed gastric emptying (DGE)
      is one of the most troublesome complications of this procedure. We developed a
      new reconstructive technique-modified subtotal-stomach-preserving
      pancreaticoduodenectomy (SSPPD) with pancreaticogastrostomy--for preventing DGE.
      We consider our reconstructive technique to be one of the most favorable
      procedures for preventing DGE in patients who have undergone
      pancreaticoduodenectomy with pancreaticogastrostomy.

PMID- 19579646
TI  - [The involvement of the apothecaries of Nancy in the medical consultation of the
      Royal College of Medicine, from 1764 to 1793].
AB  - A medical consultation reserved to poor sick persons of countries around Nancy
      was organized by the Royal College of Medicine from 1752. Concerning the drugs,
      the College thout first to use an apothecary companion, then it agreed, in 1764,
      with the proposal of the apothecaries of the city to distribute them free of
      charge, each in turn for two months, one in winter and one in summer. In 1788,
      the apothecaries complained from the abuses committed in the writing of the
      consultation tickets. The gardener had to furnish plants, gratuitously or not, in
      order the consultants to prepare drugs at home. These practices lasted until the
      extreme end of year 1793 where the College was cancelled.

PMID- 19579645
TI  - Weekly paclitaxel therapy is effective for gastric adenosquamous carcinoma: a
      case report.
AB  - A 65-year-old man was admitted for epigastralgia. On endoscopy, a type 3 cancer
      from the lower body of the stomach to the antrum was found, and abdominal CT scan
      demonstrated multiple liver metastases and peritoneal dissemination. A distal
      gastorectomy was performed. On, pathological examination, a diagnosis of
      adenosquamous carcinoma was confirmed, and lymph node metastases around the
      perigastric areas were found. The patient was given chemotherapy consisting of S
      1 alone (120 mg/day, days 1-28 with two weeks rest). After two courses of
      chemotherapy, his liver metastases were found to have progressed, and paclitaxel
      was given at a weekly dose of 80 mg/m2 for 3 weeks, followed by a one-week rest.
      The carcinoembryonic antigen level decreased remarkably, and the liver metastases
      had decreased on CT. Thus, extensive chemotherapy for the liver metastases
      improved the patient's prognosis, while maintaining his quality of life.

PMID- 19579647
TI  - [The library of an apothecar at the end of the XVIIIth century].
AB  - The library of Pierre Boitel, described in the incentory of his property include
      250 books and more than 423 volumes. The importance in number and in diversity
      shows the evolution from apothecary to pharmacist. The scientific space of this
      library enlighten the instructions of the future schools of pharmacy.

PMID- 19579648
TI  - [Professor Emile Perrot: seven years of active collaboration with the journal La
      Quinzaine coloniale (1907-1914)].
AB  - E. Perrot, at that time young professor of Pharmacy in Paris, realizes in 1907
      the interest of the valorization of the french colonial empire. He is then part,
      during 7 years, of the authors for the journal "La Quinzaine coloniale" where he
      is among the ones that publish in a new section related to scientific and
      technical publications with the objective to emphatize colonial ressources.
      Perrot approaches many subjects from rubber to medicinal herbs (especially
      quinquina) as well as babanas and botanic gardens. In doing it, it is an
      opportunity for Perrot to give some ideas on how to improve the valorization of
      french colonies, ideas that will be at least partially applied after the 1st
      World War when he became vice-president of the "Comite Interministeriel des
      Plantes Medicinales" created in 1918. The 300 articles that was published at the
      time by Perrot is an opportunity to better assess the role of E. Perrot later on,
      during the period 1918-1939.

PMID- 19579649
TI  - [Little histories of magnetic cures].
AB  - Men were very early fascinated by magnetism because of its manifest and
      particular working at distance, which looked different of gravity. It was tryed
      to be explained by mecanism, for exemple Descartes and Boyle. Paracelse valued
      the therapeutics with magnets and conceived medicines as working by a magnetic
      virtue. Gilbert limited the medicinal properties of magnet but helded it to be
      animated. Many authors praised remedies that work at distance of the evil as
      Bacon, Van Helmont, Croll, Porta, Goclenius, Digby. Such a belief related to
      magic ideas of this time. In the Bacon's way Boyle collected facts of magnetic
      cures, and his actual testing of the divisibility of bodies led him to conceive
      imponderable corpuscles. Newton supposed a subtil and universel fluid going
      through every solid body. Mesmer misappropriated this idea by founding the animal
      magnetism of which physical working was only proceeding from the inside of the
      patient by an effect of suggestion (psychosomatic). Homeopathy took again the
      notion of remedies having an infinite or a magnetic virtue, which partly issued
      from Paracelse's and Mesmer's doctrines, which were extolled in Germany at the
      time of Hahnemann. The latter decided in favour of a spiritualist and not
      corpuscular interpretation of the working of his homeopathic medicines.

PMID- 19579650
TI  - [Spanish purgatives waters "made in France"].
AB  - Before the First world War, many french societies exploited spanish purgatives
      watters. The watter was drawn in Spain, but it was bottled in France for many
      reasons. The authors of this article explain the beginnings of exploitation of
      three of the most famous purgatives watters: Rubinat source Llorach, Carabana and
      Villacabras.

PMID- 19579651
TI  - [Drugs Bazar of Constantinople].
AB  - A long while in The Egyptian Bazaar in Istanbul, which was one of the high place
      of oriental medicine and pharmacopoeia, were established the most famous
      apothecaries (aktar), herborists, manufacturers and merchants of perfumes, and so
      merchants of cotton. With that of Bursa, it was one of the greatest trade center
      for plants, drugs and exotic spices, uncommon and expensive. The products were
      landed along the southerly water-side of the Golden Horn. The travellers, who
      discovered with astonishment all the scents of Orient, the aromatic drugs, the
      mysterious perfumes, were charmed and most of them described particularly and in
      details this Drugs Bazar of Constantinople in their travelbooks. To day, the
      merchants of spices (baharatci) who are in this place offer to their clients a
      large choice of aromatic products, homemade specialities and traditional
      medicines.

PMID- 19579652
TI  - Workers do the shuffle.

PMID- 19579653
TI  - Beyond nursing: hot healthcare jobs.

PMID- 19579654
TI  - Cryoprotection and cryosterilization effects of type I antifreeze protein on E.
      coli cells.
AB  - To establish the effects of type I antifreeze protein (AFP) on E. coli cells, we
      have focused on the survival rate of the E. coli cells using type I AFP at
      various concentrations under rapid cooling conditions using liquid N2 at
      atmospheric or low pressure. The survival rate of E. coli was enhanced by the
      addition of type I AFP at a concentration of 10 microg/ml, and its value shifted
      from 0.73% to 2.96%. When the concentration of type I AFP was 100 microg/ml, the
      cell survival rate markedly decreased to 0.090%. This low survival rate was
      further decreased (0.022%) by the application of the same freeze-thaw treatment
      for four times. Also, the effect of type I AFP as a bactericidal agent did not
      vary according to the varying initial cell densities from 10(4) to 10(8) cells /
      ml. Furthermore, the effects of using type I AFP at 1.0 MPa with N2 gas under
      conditions of low pressure and low oxygen tension using a simple device were
      examined. When the actions of type I AFP as a cryoprotectant were stimulated, the
      survival rate of the E. coil cells increased to 57.8%. In addition, the
      bactericidal effect of type I AFP at 100 micro g/ml of protein concentration
      could also be enhanced. The survival rate using 100 g/ml of type I AFP under low
      pressure was 0.35% of that using 10 microg/ml under the same conditions. This is
      the first report on the cryoprotectant and cryosterilization effects of type I
      AFP of E. coli cells under various conditions.

PMID- 19579655
TI  - Impact of unnatural nucleosides on the control of microbial growth.
AB  - This research investigated the antimicrobial activities of unnatural nucleosides.
      We tested the MIC and MBC of 17 synthetic nucleoside analogues against 10
      microbial strains. These nucleoside analogues were classified into four groups
      according to their structural characteristics. Inhibition was observed with
      compounds 1-1, 3-1, and 4-3. In particular, 5'-deoxythymidine (3-1) was most
      effective at 50 micro g/mL against Bacillus subtilis and Staphylococcus aureus.
      This analogue has had the hydroxyl group at the 5' position replaced with a
      hydrogen atom. All compounds had weak effects against various species of mold.
      The MBC of 5'-deoxythymidine was 50 g/mL in 0.5 h against S. aureus. These
      results showed that 5'-deoxythymidine had the most effective antimicrobial
      activity of the 17 different unnatural nucleosides. The inhibitory effect of 3-1
      suggests that it may be useful as an antibacterial agent in medical situations.

PMID- 19579656
TI  - Responses of Aspergillus oryzae to stimuli from near-UV light irradiation in the
      presence or absence of titanium dioxide.
AB  - The responses of Aspergillus oryzae to the stimuli from near-UV irradiation were
      investigated by using a black light fluorescent lamp in the presence or absence
      of TiO2 particles. Light irradiation at an intensity of 6 W/m2 strongly inhibited
      the growth of germinated pellets of A. oryzae. This growth inhibition was
      weakened by TiO2 particles (0.05 g/l), especially in the initial growth phase, in
      which the expression level of catalase gene (catB) was approximately three times
      higher than that in the absence of TiO2 particles. However, the initial induction
      of catB expression by H2O2 pretreatment did not restore the growth under the
      black light irradiation. The weakening of growth inhibition is thought to result
      from alternative physiological responses of A. oryzae against stimulus by photo
      excited TiO2.

PMID- 19579657
TI  - Biofilm formation abilities and disinfectant-resistance of Pseudomonas aeruginosa
      isolated from cockroaches captured in hospitals.
AB  - Forty-five strains of Pseudomonas aeruginosa isolated from cockroaches captured
      in hospitals were investigated with regard to their biofilm-forming ability and
      resistance to various disinfectants in various cellular states. The
      hydrophobicity value varied among the test strains from 0.001 to 0.241, and the
      mean +/- standard deviation (SD) was 0.101 +/- 0.074. The relative viscosity of
      the extracellular product was measured. All test strains produced a mucous
      substance, and the value was 1.05-1.30 (mean +/- SD: 1.11 +/- 0.06), showing that
      all test strains had a biofilm-forming ability. Bactericidal experiments were
      performed using 6 disinfectants: ethanol, Hibitane, Isojin, Osvan, Tego 51, and
      Welpas. When bacteria in suspension were exposed to the disinfectants for 1 min
      (suspension test), 5 of the 6 disinfectants excluding Tego 51 completely killed
      all test strains, showing high bactericidal effects. In contrast, when adherent
      bacteria were exposed to the disinfectants for 1 min (adhesion test), the killing
      rate by Welpas was 100%, but those by Isojin and ethanol were lower (88.9 and
      60.0%, respectively), that by Osvan was only 4.4%, and no bacteria were killed by
      Hibitane or Tego 51. These findings showed that the bactericidal effects markedly
      decreased in the case of adherent P. aeruginosa.

PMID- 19579658
TI  - Antimicrobial activity of fullerenes and their hydroxylated derivatives.
AB  - The antimicrobial activities of fullerene C60 and its derivatives against 6 kinds
      of bacteria and 2 kinds of fungi were evaluated. The tested samples were water
      soluble fullerenes (polyvinylpyrrolidone (PVP)/C60, gamma-cyclodextrin (gamma
      CD)/C60, and nano-C60) and 3 types of fullerenols (C60(OH)12, C60(OH)36.8H2O, and
      C60(OH)44.8H2O). Their activities were compared with those of (+)-catechin and
      hinokitiol from the viewpoint of future application to cosmetics. Although
      pristine C60 demonstrated no antimicrobial activity, fullerenols exhibited good
      antimicrobial activity against Propionibacterium acnes, Staphylococcus
      epidermidis, Candida albicans, and Malassezia furfur. In particular, C60(OH)44
      exhibited a strong and wide-ranging antimicrobial activity comparable to that of
      catechin. This compound exhibits antimicrobial activity via inhibition of
      microbial cell growth and not via bactericidal activity.

PMID- 19579659
TI  - The rapid detection of Salmonella from food samples by loop-mediated isothermal
      amplification (LAMP).
AB  - Loop-mediated isothermal amplification (LAMP) assay was applied to the detection
      of Salmonella in food and human materials. It was possible for the assay to
      detect Salmonella within 60 min. All of 54 serovars of Salmonella tested were
      amplified, but all bacteria tested other than Salmonella were not. The LAMP assay
      could detect 10(2) cfu/ml levels of Salmonella. The specificity was similar to
      that of a PCR assay, but the sensitivity of LAMP was considered to be greater.
      Thus, the LAMP assay was confirmed to be a rapid, specific and sensitive
      detection method for Salmonella.

PMID- 19579660
TI  - Sporicidal activity of an improved iodide formulation and suggestions regarding
      the biological safety cabinet.
AB  - The sporicidal activity of an improved iodide formulation based on a previously
      reported agent (Kida et al., 2004, tentatively designated as the KMT reagent)
      which is composed of 50 mM EDTA-2Na, 50 mM ferric chloride hexahydrate
      (FeCl3.6H2O), 50 mM potassium iodide (KI) and 50% ethanol in 0.85% NaCl solution
      at pH 0.3 with hydrochloric acid, was examined in the liquid and vapor phases.
      The improved iodide formulation subject to distillation (tentatively designated
      as the distilled KMT reagent: pH around 3) showed comparable sporicidal activity
      with the KMT reagent. As for the dilution effect, dilution at 1:2 showed more
      potent sporicidal activity than the undiluted one. It achieved complete
      disinfection with a treatment for 5 min at 20 degrees C and for 60 min at 5
      degrees C. Even at a ratio of 1:100, the dilutions showed significant sporicidal
      activities at 37 degrees C. The experiment on the disinfection of the biological
      safety cabinet (Class II type A) as a practical possibility showed that
      pretreatment with 400 ml of water vapor treatment, and a mixture of 300 ml of
      this reagent and 150 ml of water in vapor phase achieved complete disinfection
      after a 24 h-decontamination process. The distilled KMT reagent may be useful for
      disinfecting against various contaminated materials and sites in both the liquid
      phase and vapor phase.

PMID- 19579661
TI  - Development of a program to fit data to a new logistic model for microbial
      growth.
AB  - Recently we developed a mathematical model for microbial growth in food. The
      model successfully predicted microbial growth at various patterns of temperature.
      In this study, we developed a program to fit data to the model with a spread
      sheet program, Microsoft Excel. Users can instantly get curves fitted to the
      model by inputting growth data and choosing the slope portion of a curve. The
      program also could estimate growth parameters including the rate constant of
      growth and the lag period. This program would be a useful tool for analyzing
      growth data and further predicting microbial growth.

PMID- 19579662
TI  - [Pain sensitivity changes in schizophrenic patients and animal models--Part II].
AB  - Diminished pain sensitivity in schizophrenic patients has been reported for more
      than 50 years, however little is known about the substrate and the basic
      mechanisms underlying altered pain sensitivity in this disease, therefore,
      relevant animal models are of decisive importance in the study of psychiatric
      diseases. The authors report a review consisting of two parts focusing on pain
      sensitivity changes in patients and in different animal models which proved the
      eligibility as schizophrenia models and pain sensitivities have also been
      determined. The second part of this article analyzed the results regarding knock
      out mice as schizophrenia models. These data proved that several genes have
      significant role in the pathomechanism of schizophrenia; therefore deficiency in
      one gene does not produce animals showing all signs of this disease. As regards
      the pain sensitivity changes, only a few data are available with controversial
      results. Data originated from complex chronic animal models indicate that they
      might be more adequate methods for studying the mechanisms of schizophrenia
      including the pain-sensitivity changes.

PMID- 19579664
TI  - [Hypertension and its therapy in the acute phase of stroke].
AB  - The elevation of blood pressure above normal and premorbid values within the
      first 24 hours of symptom onset in patients with stroke is relatively common.
      This acute hypertensive response is usually managed by different group of
      physicians, including general practitioners, emergency physicians, neurologists,
      internists, intensivists. Management strategies of this phenomenon vary
      considerably. The first consideration in blood pressure management in this
      clinical setting is to determine whether the patient might be a candidate for
      thrombolytic therapy. For those patients are not entitled to that therapy
      premorbid blood pressure values and the type of stroke are the key data for
      sufficient control of hypertension. In patients with chronic hypertension, the
      lower end of the autoregulation curve is shifted toward high pressure and an
      impaired autoregulation due to acute stroke may increase the risk for further
      brain tissue damage if the blood pressure is inadequately controlled. The current
      guidelines recommend lowering blood pressure in patients with an intracranial
      haemorrhage below 160-180/100-105 mmHg, if the patient is normotensive, while the
      target level is 180/105 mmHg in hypertensive patients. However, in ischaemic
      stroke no treatment is recommended if systolic blood pressure <220 mmHg and/or
      diastolic blood pressure <120 mmHg in the acute stage. Clinical studies are rare
      which assess the effectiveness of different antihypertensive drugs in acute
      stroke. The first strong evidence came from the ACCESS (The Acute Candesartan
      Cilexetil Therapy in Stroke Survivors) trial which suggested that a 7-day course
      of candesartan after an acute ischaemic stroke significantly improves
      cardiovascular morbidity and mortality.

PMID- 19579663
TI  - [Genetics and present therapy options in Parkinson's disease: a review].
AB  - In the past years, six monogenic forms of Parkinson disease have clearly been
      associated with this movement disorder. The most frequent forms are LRRK2- and
      Parkin-associated Parkinson disease. Currently, a genetic diagnosis does not
      change the therapy, the genes involved in genetic Parkinson disease help to
      understand the underlying pathophysiologic mechanisms of Parkinson disease.
      Beside the overview of the molecular-genetic basis, we give a review about
      genetic testing, pharmacological and other multidisciplinary treatment options.

PMID- 19579665
TI  - 99-mTc-HMPAO single photon emission computed tomography examinations in
      genetically determined neurometabolic disorders.
AB  - The aim of our study was to determine regional cerebral blood flow (rCBF)
      abnormalities in different types of enzymopathies. PATIENTS AND METHODS: Among
      the patients with genetically determined enzymopathies 3 patients had
      aminoacidopathies, and 11 had different types of encephalopathies, from which 10
      had mitochondrial encephalomyopathy (MEMP), and 1 patient had hyperuricaemic
      encephalopathy. Besides the mentioned 14 patients, 1 had ceroid lipofuscinosis
      and another patient had tuberous sclerosis. The further distribution of the MEMP
      patients' group was the following--5 patients had MEMP with lactic acidosis, 5
      had Leigh's disease (subacute necrotizing encephalopathy), from which 1 had
      cytochrome-c-oxidase deficiency (COX). Additionally in all patients were
      performed cerebral MRI and SPECT examination 10 min. after intravenous
      administration of 20 Mbq/kg 99 mTc-HMPAO. RESULTS: Fourteen out of 16 SPECT
      findings were pathologic, showing decreased focal
      frontal/temporal/temporoparietal cerebral blood perfusion. Aminoacidopathic group
      -all the 3 patients revealed pathologic signs from the aminoacidopathic patients'
      group. Among them the ornithine transcarbamylase (OTC) heterozygous female
      patient with left-sided hemiparesis caused by hyperammonemic stroke at 10 month
      age, showed right sided temporoparietal, occipital and left frontal
      hypoperfusion, nearly 6 years after the cerebral vascular attack. This finding
      might be resulted because of diaschisis. Mitochondrial encephalo-myopathic (MEMP)
      group--all the four patients with MEMP and lactic acidosis showed focal
      hypoperfusion in the temporal region, while the perfusion was normal in the COX
      deficient patient and in 2 Leigh's disease (subacute necrotizing encephalopathy)
      patients. In the remaining 1 Leigh's patient frontotemporal hypoperfusion was
      found. In all patients there were non specific structural abnormalities detected
      by MRI: cortical and subcortical atrophy, and scattered demyelination foci. In
      the case of ceroid lipofuscinosis the MRI showed cerebral atrophy and cerebellar
      hypoplasia, and the SPECT showed right frontal and occipital hypoperfusion,
      bilateral parietal physiological riping process. The patient with tuberous
      sclerosis showed bilateral temporo-occipital hypoperfusion. CONCLUSION: (1) SPECT
      images demonstrated hypoperfusion rCBF changes in 14 out of all 16 patients. (2)
      Regional cerebral/cerebellar hypoperfusion was detected by SPECT in mitochondrial
      encephalomyopathies, with lactate acidosis and aminoacidopathies giving high
      informative value about the cerebral perfusion.

PMID- 19579667
TI  - [Severe intracranial hypotension in an adolescent with Marfan syndrome. Case
      report].
AB  - Spontaneous intracranial hypotension is a rare complication of connective tissue
      disorders. One of them is Marfan syndrome. It predisposes the patient to
      meningeal diverticula. Possibly after minor unrecognised head trauma or secondary
      to Valsalva manoeuvre cerebrospinal fluid leak from meningeal diverticula can
      happen. It causes postural headache. We describe a 15 year old adolescent female
      newly diagnosed with Marfan syndrome, who presented with intractable postural
      headache. Our patient's brain MRI showed bilateral frontal subdural effusion,
      narrow ventricles, downward displacement of the brainstem, enlarged cervical
      venous plexi, dural ectasias and wide nerve root sleeves. Radionuclide
      cisternography demonstrated CSF leaks at multiple sites. She could not be treated
      conservatively, but was successfully treated by epidural saline injections.
      Control brain and cervical MRI confirmed her healing, too. At the two and half
      year follow up visit, she was completely well. So we recommend this easy
      technique to be used before epidural autologous blood patches.

PMID- 19579666
TI  - [Long term experience with Stalevo in Szeged, Hungary].
AB  - The triple combination of levodopa, DDCI and entacapone (Stalevo) is used to
      treat motor complication in patients with Parkinson's disease. In this study we
      summarized the clinical data of our patients treated with Stalevo for the longest
      period. We can concluded, that after switching to Stalevo due to wearing off, the
      average levodopa doses were lower then before and the motor complications were
      milder. After 3 years of Stalevo therapy the levodopa doses were increased but
      still did not reach the average doses before introducing Stalevo. After switching
      the patients' general well-being was improved as indicated by the visual analogue
      scale. In summary, the Stalevo treatment is safe and effective for long run and
      improves the patients' quality of life.

PMID- 19579668
TI  - [Surgical treatment of resistant epilepsy, caused by hemispherical dysgenesis-
      case report].
AB  - A part of patients with the therapy resistant epilepsy can be cured by surgical
      interventions. The more concordant the presurgical evaluation data, the better
      prognosis the patient has postoperatively. In case of discordant examination
      data, multimodal evaluation or case-specific decision might be successful. We
      report on a five-year-old boy with bilateral (left-dominated) cortical dysplasia
      and therapy resistant epilepsy. The ictal EEG did not help to localize the
      seizure onset zone, semiology had little lateralization value; however, FDG-PET
      showed left hemispheric hypermetabolism. The child became almost seizure-free and
      showed improved development after left-sided hemispherotomy.

PMID- 19579669
TI  - [Posterior ischaemic optic neuropathy].
AB  - Here one case report of the posterior ischaemic optic neuropathy, a rare and
      underdiagnosed form of the non arteritic ischaemic optic neuropathy is presented,
      to underline the value of the MRI in the diagnosis. The ischaemic optic
      neuropathy is the infarction of the optic nerve. Depending on the affected
      segment of optic nerve (optic nerve head or retrobulbar segment) two subclasses
      exist: the anterior (AION) and the posterior (PION) ischaemic optic neuropathy.
      Ischaemic optic neuropathy characterized by sudden, painless, mononuclear loss of
      vision, and/or visual field defect, that is accompanied by a diagnostic picture
      of the optic disc fundus only in the case of the AION. The diagnosis of the PION
      is based on a diagnosis of exclusion described by Hayreh in 1981. The macular and
      retinal lesions, the etiological role of toxic agent, the compression and the
      inflammation of the optic nerve all have to be excluded. The differential
      diagnosis between the PION and the retrobulbar neuritis is more difficult.
      Nowadays, in addition to the case history and the clinical data the diagnosis of
      the PION could be confirmed with help of VEP (visual evoked potential) and MRI.
      In the case of an old woman who had a sudden, painless visual loss of left eye we
      confirmed the diagnosis of PION with MRI which was presumed after had excluding
      other etiological factors.

PMID- 19579670
TI  - [Factual contributions to the history of neuropsychiatry--Szent Istvan Korhaz,
      Budapest (1885-2008)].

PMID- 19579671
TI  - [Stroke prevention: the role of carotid stenting and antithrombotic therapy].

PMID- 19579672
TI  - Improve or lose. Maryland pegs reimbursement to reducing complications for 52
      conditions.

PMID- 19579673
TI  - Isotopes on the ropes. Molybdenum-99 shortage has some clamoring for U.S.
      production.

PMID- 19579674
TI  - Marginal improvement. Don't expect pay-for-performance programs to solve quality,
      cost problems.

PMID- 19579675
TI  - Retail rumble. MinuteClinic faced a tough fight in opening outlets in Mass., and
      it's still not welcome in Boston.

PMID- 19579676
TI  - Walking on golden eggshells. Some Calif. hospitals sweating seismic mandates.

PMID- 19579677
TI  - More data + less care = lower cost + better health.

PMID- 19579678
TI  - Calorie-conscious menus.

PMID- 19579679
TI  - Dads are dudes.

PMID- 19579680
TI  - The emergence of a community mapping network: coastal eelgrass mapping in British
      Columbia.
AB  - The purpose of this paper is to document and theorize the emergence of a network
      of stewards concerned about the conservation of a marine habitat called eelgrass
      along the coastline of British Columbia, Canada. Today, by engaging as
      professional biologists, government employees, and volunteers using various
      mapping, outreach, and communication tools, these stewards generate knowledge on
      the geographic location and health of eelgrass habitat, how to educate the
      public, how to coordinate volunteers, and how to approach local governments--with
      the ultimate goal of convincing others that eelgrass is worth protecting. Our two
      year ethnographic study began in the second year of a project that was designed
      to train twenty community coordinators how to map and monitor eelgrass habitat.
      The coordinators were faced with complex social, cultural, political, historical,
      and material landscapes--which made us wonder about how it was possible for the
      network to hold together while extending its reach. We provide evidence to
      support the claim that the network became more stable and was extended by
      particular performances. These performances emerged from recognition and
      resolution of resistances, in which the network was both resource for and object
      of its activity. In the process, (a) knowledge produced is made to move and do
      something, (b) coordinators and scientists involved acted as knowledge brokers
      between various communities, and (c) communication between coordinators was
      enabled and maintained.

PMID- 19579681
TI  - Designer babies on tap? Medical students' attitudes to pre-implantation genetic
      screening.
AB  - This paper describes two studies about the determinants of attitudes to pre
      implantation genetic screening in a multicultural sample of medical students from
      the United States. Sample sizes were 292 in study 1 and 1464 in study 2.
      Attitudes were of an undifferentiated nature, but respondents did make a major
      distinction between use for disease prevention and use for enhancement. No strong
      distinctions were made between embryo selection and germ line gene manipulations,
      and between somatic gene therapy and germ line gene manipulations. Religiosity
      was negatively associated with acceptance of "designer baby" technology for
      Christians and Muslims but not Hindus. However, the strongest and most consistent
      influence was an apparently moralistic stance against active and aggressive
      interference with natural processes in general. Trust in individuals and
      institutions was unrelated to acceptance of the technology, indicating that fear
      of abuse by irresponsible individuals and corporations is not an important
      determinant of opposition.

PMID- 19579682
TI  - Perceptions, knowledge and ethical concerns with GM foods and the GM process.
AB  - Compared to their European counterparts, the American public has been
      characterized as relatively unknowledgeable and indifferent about genetically
      modified foods. To evaluate these claims, six focus groups were held in three
      Arkansas cities to: (1) determine the extent of knowledge the public possesses
      about genetically modified foods; (2) detail perceived benefits and risks
      associated with agricultural biotechnology applications; and (3) explore lay
      perceptions about the genetic modification process itself. Participants
      demonstrated partial knowledge, and tended to overestimate the number of
      genetically modified foods. However, participants tended to be familiar with
      debates surrounding benefits, risks and moral issues associated with agricultural
      biotechnology applications. Findings also showed that while participants were not
      overly concerned about combining genes between plants, they were concerned about
      inserting animal genes into plants. If these results are any indication, moral
      and ethical issues will dominate any discussion of foods derived from a mixture
      of animal and plant genes.

PMID- 19579683
TI  - Guardians of our future: New Zealand mothers and sustainable biotechnology.
AB  - In year two of a three-year project, New Zealand mothers of children aged 10 and
      under were interviewed to examine the social, cultural and spiritual dimensions
      of biotechnology. Ten focus groups were conducted and used "sustainable
      biotechnology" as a center-point for discussion, concentrating on four different
      biotechnology scenarios. The findings of the research were consistent with year
      one and with findings on the general public throughout the world. Further
      insights revealed in year two suggested that women saw their and future
      generations' quality of life as intimately intertwined with the health of the
      environment, making the environment particularly important. Because of this,
      anything that had potentially negative consequences on the ecosystem was
      perceived to pose a threat to the woman, her family and future generations. The
      need for strict controls to be put in place by regulatory and research
      authorities was therefore seen as an important step in allaying her fears. True
      partnership and participation was seen as critical, since it would only be by
      such means that mothers would feel they were in control of the safety of their
      own children.

PMID- 19579684
TI  - The extinct animal show: the paleoimagery tradition and computer generated
      imagery in factual television programs.
AB  - Extinct animals have always been popular subjects for the media, in both fiction,
      and factual output. In recent years, a distinctive new type of factual television
      program has emerged in which computer generated imagery is used extensively to
      bring extinct animals back to life. Such has been the commercial audience success
      of these programs that they have generated some public and academic debates about
      their relative status as science, documentary, and entertainment, as well as
      about their reflection of trends in factual television production, and the
      aesthetic tensions in the application of new media technologies. Such discussions
      ignore a crucial contextual feature of computer generated extinct animal
      programs, namely the established tradition of paleoimagery. This paper examines a
      selection of extinct animal shows in terms of the dominant frames of the
      paleoimagery genre. The paper suggests that such an examination has two
      consequences. First, it allows for a more context-sensitive evaluation of extinct
      animal programs, acknowledging rather than ignoring relevant representational
      traditions. Second, it allows for an appraisal and evaluation of public and
      critical reception of extinct animal programs above and beyond the traditional
      debates about tensions between science, documentary, entertainment, and public
      understanding.

PMID- 19579685
TI  - Defining issue-based publics for public engagement: climate change as a case
      study.
AB  - Understanding your audiences' perceptions is key to the success of any
      communication campaign. This research note outlines a pilot study using the
      Situational Model of publics to segment the broader public. Focus groups were
      used to study publics' understandings and perceptions of climate change to
      determine if this issue-based publics model is relevant to this field. The work
      shows the potential of this model of publics, but in the case of climate change
      it may need a minor refinement.

PMID- 19579686
TI  - The (im)balance of nature: a public perception time-lag?
AB  - The last two decades have seen a conceptual shift within environmental and social
      sciences from an emphasis on ecosystem stability and balance to an
      acknowledgement of the importance of flux and change in the natural world. This
      has profound implications for conservation management and policy and has driven
      an (incomplete) transition from managing to maintain (bio)diversity and
      ecological stability at some historically derived "optimum" to managing to
      maintain important ecosystem and evolutionary processes such as nutrient cycles
      and migration. Here, we investigate whether this change from a "balance of
      nature" metaphor to a more dynamic perspective ("flux of nature") is reflected in
      the representation of conservation and ecosystem management in the news media,
      the Internet, and the academic literature. We found that the media and the global
      Internet community still portray the aim of conservation science and of
      conservationists as being one of maintaining stability, harmony and balance.

PMID- 19579687
TI  - Adolescent responses toward a new technology: first associations, information
      seeking and affective responses to ecogenomics.
AB  - This paper reports on an exploratory study among adolescents (N = 752) who were
      introduced to the emerging technology of ecogenomics for the first time. An
      online survey focused on their associations with the term ecogenomics, their
      planned information seeking behaviors if they were to acquire information about
      the new technology, and their first affective responses toward ecogenomics after
      having read some introductory information about it. Adolescents were found to
      associate ecogenomics most frequently with economy. Although the Internet was the
      most popular medium to be used in their planned information seeking behaviors,
      books and science communication professionals were judged as the most trustworthy
      information sources. After having read the introductory information about
      ecogenomics most adolescents reported positive affective responses toward the new
      technology.

PMID- 19579688
TI  - Prevalence of antiretroviral drug resistance in untreated persons newly diagnosed
      with HIV-1 infection.
AB  - Current knowledge of HIV-primary resistance indicates that the prevalence of
      transmitted resistant strains has increased to substantial levels over the past
      few years, with a wide variation depending upon a number of factors. New
      infections with a virus strain already resistant to antiretroviral drugs, namely
      non-nucleoside reverse transcriptase inhibitor (NNRTI), have a negative impact on
      initial treatment response and also shorten the time to first virologic failure.
      The aim of this study was to determine the prevalence of antiretroviral drug
      resistance by a genotypic test in a population with newly diagnosed HIV-1
      infection at a clinical centre in Bologna between June 2006 and September 2007.

PMID- 19579689
TI  - Serological response in cattle immunized with inactivated oil and Algel adjuvant
      vaccines against infectious bovine rhinotracheitis.
AB  - Infectious bovine rhinotracheitis (IBR) virus was grown in Madin Darby bovine
      kidney (MDBK) cell line using a roller culture system for its large-scale
      production. Optimum multiplicity of infection (MOI) of 1:750 was found to give
      consistent virus yield. To determine the appropriate payload, three batches of
      antigen with virus titres ranging from 10(8.37) to 10(6.37) TCID50 per ml were
      used to prepare experimental inactivated IBR oil adjuvant vaccine. Beta
      propiolactone (BPL) was used as inactivant. The vaccine formulation using
      inactivated BHV-1 virus antigen with a pre-inactivation titer of 10(8.37) TCID50
      per dose elicited better sero-conversion in cattle calves as evidenced from the
      mean log SN titre of 1.02. To choose the appropriate adjuvant, two batches of
      vaccine each containing aluminum hydroxide gel (Algel) and Montanide oil
      respectively were tested in calves. Two groups of 16 calves each were inoculated
      with Algel and oil adjuvant vaccine respectively twice at four weeks to test the
      immunogenicity. Adequate titres of vaccine induced anti BHV-1 antibodies could be
      demonstrated both by ELISA and MNT up to 180 days post vaccination in both the
      groups.

PMID- 19579690
TI  - Simultaneous detection of viruses and Toxoplasma gondii in cerebrospinal fluid
      specimens by multiplex polymerase chain reaction-based reverse hybridization
      assay.
AB  - The lack of rapidity and the low sensitivity and specificity of traditional
      laboratory methods limits their usefulness in the laboratory diagnosis of viral
      central nervous system (CNS) infections. This study describes the use of a
      commercially available multiplex polymerase chain reaction (mPCR)-based reverse
      hybridization assay (RHA) for the simultaneous detection of the genomes of 8
      viruses and Toxoplasma gondii in cerebrospinal fluids (CSF) from 181 patients
      suspected of having viral meningitis. Twenty-two/181 (12.15%) CSF samples
      resulted positive by mPCR. Eighteen/22 were positive for 1 viral pathogen,
      whereas a dual infection was detected in 4/22 samples. Epstein-Barr virus (EBV)
      was the most commonly detected virus (6/22), followed by herpes simplex virus
      type-1 (HSV-1) (5/22) and -2 (HSV-2) (4/22). Cytomegalovirus (CMV), human
      herpesvirus-6 (HHV-6), and Epstein-Barr virus (EBV) were detected in 1 specimen
      each. Two CSF samples were co-infected by HSV-1/HSV-2, 1 sample by HHV-6/T.
      gondii, and 1 sample by EBV/EV, respectively. Our data support the usefulness of
      mPCR as a rapid molecular method for the simultaneous detection of major viral
      pathogens and T. gondii in aseptic meningitis also to allow the earlier
      application of specific antiviral therapy.

PMID- 19579691
TI  - Mutations in the rpoB gene of rifampin-resistant Mycobacterium tuberculosis
      isolates from Eastern Poland.
AB  - This study investigated mutations in the rpoB gene of rifampin-resistant isolates
      obtained from patients living in Eastern Poland. A total of 37 phenotypically
      and/or genotypically confirmed M. tuberculosis rifampin-resistant clinical
      isolates were included in this study. The strains were selected from symptomatic
      patients with a diagnosis of pulmonary and extrapulmonary tuberculosis. A line
      probe assay kit (INNO-LiPA rif Tb) was used for any specific mutational pattern
      of rpoB gene. Our data support the common notion that rifampin resistance
      genotypes with mutation at a critical codon, i.e. the one encoding Ser-531, is
      frequent in M. tuberculosis populations regardless of geographic origin. Our
      findings also suggest that in a geographic area such as Eastern Poland less
      common mutations of the rpoB gene occur more frequently. The frequency of
      substitution at codon 526 (His-Asp) was found to be high in Lublin. This study
      indicates that mutations associated with nucleotide replacements in codons 526
      (His-Asp) and 531 (Ser-Leu) were associated with a high percentage of RMP
      resistance, whereas mutations in codons 516 (Asp-Val) and 526 (His-Tyr) were
      observed in a low percentage of RMP-resistance.

PMID- 19579692
TI  - Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium
      tuberculosis in Turkey.
AB  - Mutations in the pyrazinamidase (PZase) gene (pncA) are considered the major
      mechanism of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. The aim
      of this study was designed to determine pncA mutations among ten PZA resistant
      and two PZA susceptible M. tuberculosis strains from Turkey and also to compare
      the PZase activity of them with the genotype. All isolates were identified by
      BACTEC NAP (P-nitro-alpha-acetylamino-beta-hydroxy-propiophenone) test and PCR
      RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism)
      method. Drug sensitivity tests were performed by BACTEC system. PncA mutations
      were detected by DNA sequence analysis. No mutation was detected in two PZA
      susceptible and three out of ten PZA resistant strains. While, two of the PZA
      resistant strains had mutations in the same region (Gly24Asp), two of the PZA
      resistant strains had mutations in different regions (Thr160Lys), (His51Pro).
      Three of the PZA resistant strains had frameshift as a 167 bp deletion at
      nucleotide position 102. As a result, we detected two new mutations and a
      frameshift which may be responsible for PZA resistance in this study different
      from the other studies which previously 51st codon mutation was reported.

PMID- 19579693
TI  - A natural pertactin deficient strain of Bordetella pertussis shows improved entry
      in human monocyte-derived dendritic cells.
AB  - The invasion and the immunomodulatory effect of a Bordetella pertussis natural
      deficient strain 00141(PRN-) on human dendritic cells (MDDC) and its in vivo
      infection ability in a mouse model were evaluated in comparison with the
      reference B. pertussis strain ATCC 97-97 (18323). The mutant was isolated from a
      case of pertussis which occurred in a 22-month-old infant with typical symptoms
      of the disease. The results showed that this natural B. pertussis PRN deficient
      strain presented higher invasion ability of human MDDC compared to the reference
      strain. This natural mutant similar to the B. pertussis reference strain had
      immunomodulatory properties, inducing maturation in the DC phenotype which
      resulted in the acquisition of potent T cell-activating properties and down
      regulated IL-12 production, and secretion of IL-10. The ability of PRN- strain to
      infect the lungs of CD1 mice was comparable to the reference strain and no
      difference was observed in the kinetics of clearance. Overall, these results show
      that the enhanced ability of the PRN- strain to invade/infect MDCC suggest that
      the PRN antigen may play a role in survival of the microorganism in the host.

PMID- 19579695
TI  - TNF-alpha, TGF-beta, IL-10, IL-6 and IFN-gamma gene polymorphisms as risk factors
      for brucellosis.
AB  - Polymorphisms in the regulatory regions of cytokine genes can affect the level of
      cytokine production, and may be associated with predisposition to infectious
      diseases as well as different clinical outcomes. The aim of this study was to
      investigate the association of the polymorphisms of IL-6 (-174), IL-10 (-1082, 
      819), IFN gamma (+874), TGF beta (codon 10, codon 25) and TNF alpha (-308) genes
      with brucellosis in terms of susceptibility and resistance to the disease or
      occurrence of focal complications. A case control study was carried out in 85
      patients with brucellosis and 85 healthy controls. We studied the polymorphisms
      of IL-6, IL-10, IFN-gamma, TGF-beta 1 and TNF alpha genes, using the polymerase
      chain reaction with sequence-specific primers. The IL-10 CT, TGF-beta 1 codon 10
      CC and TGF-beta 1 codon 25 GG genotypes were significantly more frequent in the
      patients compared to the controls. The IL-10 CC genotype was higher in the
      controls than in the patients. In addition, the IL-6 (-174) GG genotype was more
      frequent in the patients without focal forms, while the GC genotype was more
      frequent in the patients with focal forms. Our results showed that polymorphisms
      of IL-10 (-819) and TGF beta 1 codons 10 and 25 were associated with
      susceptibility or resistance to brucellosis. The IL-6 (-174) GC genotype may be a
      risk factor for the development of focal complications of brucellosis, whereas
      the GG genotype may be a protective factor against brucellosis.

PMID- 19579694
TI  - Resistance to disinfection of a polymicrobial association contaminating the
      surface of elastomeric dental impressions.
AB  - The aim of this study was to evaluate the ability to resist disinfection of a
      polymicrobial association contaminating the surface of dental impressions
      obtained with two different elastomers: a polyether (Impregum) and an addition
      polymerized silicone (Elite). Impressions were contaminated with a mixture of
      three biofilm-forming microorganisms (Staphylococcus aureus, Pseudomonas
      aeruginosa and Candida albicans) and disinfected immediately after contamination,
      or after microbial layers were allowed to develop during a six-hour storage. Two
      commercial disinfectants were tested: MD 520 containing 0.5% glutaraldehyde and
      Sterigum Powder without glutaraldehyde. Residual contamination was recovered by
      mechanical rinsing immediately after disinfection and after a six-hour storage of
      disinfected impressions, and assessed by colony counting. Both disinfectants
      tested were shown to be effective in reducing the microbial presence on the
      impression materials, achieving at least a 102 reduction of microbial counts
      compared to water rinsing. However, Sterigum was generally less effective on the
      Elite elastomer and could not grant disinfection on six-hour aged P. aeruginosa
      and C. albicans microbial layers. The results of this study suggest that the
      materials used for the impressions influence the efficacy of disinfection.
      Disinfectants should be tested according to conditions encountered in everyday
      clinical practice and the need for immediate disinfection of impressions should
      be clearly indicated by manufacturers.

PMID- 19579696
TI  - Direct antifungal susceptibility testing of positive Candida blood cultures by
      sensititre YeastOne.
AB  - Invasive candidiasis is associated with high morbidity and mortality. Differences
      in the virulence and susceptibility of the various Candida spp. to antifungal
      drugs make the identification and rapid MIC determination very important for
      clinical management. The aim of this study was to improve the turnaround time
      (TAT) for antimicrobial test generation by susceptibility testing directly from
      the bottle of blood culture positive for yeasts, circumventing the isolation
      process and thereby generating an accurate antifungal MIC determination as
      quickly as possible. Sensititre YeastOne was used by direct inoculation from
      positive blood culture bottles in 40 cases of candidaemia. All the results were
      compared with those obtained using standard laboratory procedures after
      subculturing from a positive bottle onto solid media. The results obtained from
      direct inoculation of Sensititre YeastOne compared with tests carried out using
      standard procedures show that out of a total of 40 strains tested no very major
      errors or major errors and only 4 minor errors occurred (98% agreement rate out
      of a total of 240 drug/bug combinations tested), thus generating an accurate
      antifungal MIC determination and saving an average time of 24 hours compared with
      the time required for the standard procedures traditionally used.

PMID- 19579697
TI  - Searching for HAdV-52, the putative gastroenteritis-associated human adenovirus
      serotype in Southern Hungary.
AB  - Human adenovirus (HAdV) serotype 52 has recently been discovered in the United
      States in samples from human patients with gastroenteritis of unknown etiology
      and is suspected to be a new human enteric pathogen. The aim of the present pilot
      study was to investigate whether this virus is circulating in the population of
      Southern Hungary by screening stool specimens collected from gastroenteritis
      cases and communal sewage samples in the area of Baranya County. A total of 209
      diarrheic stool (124 from children and 85 from adults) and 45 influent sewage
      samples were screened for HAdV-52 by PCR using a primer pair specific to the gene
      of 12.5K protein in the E3 genomic region. The novel human adenovirus was not
      detected in any of the tested samples, suggesting that HAdV-52 was not
      circulating in the target population and the area during the study period. Since
      temporal and geographical fluctuations may markedly affect the epidemiology of
      human enteric pathogens, additional investigations are required to gain more in
      depth insights into the ecology of this novel adenovirus.

PMID- 19579698
TI  - Detection of PARV4, genotypes 1 and 2, in healthy and pathological clinical
      specimens.
AB  - The molecular epidemiology and tissue distribution of Human Parvovirus 4 (PARV4)
      and its variant PARV5 (Parvoviridae family) are poorly known. The aim of this
      study was to investigate the epidemiological role and prevalence of PARV4/5 by a
      nested-PCR on different clinical specimens, including blood samples from healthy
      donors, healthy and pathological skin samples, and bronchoalveolar lavages (BAL).
      Among blood specimens, 2/53 were positive; 3/37 and 23/105 of healthy and
      pathological skin specimens resulted positive, respectively, whereas no BAL was
      positive. PARV4/5 may be present in different healthy and pathological samples,
      suggesting the need for further investigating its tissue distribution.

PMID- 19579699
TI  - Prevalence of viral hepatitis and molecular analysis of HBV among voluntary blood
      donors in west Iran.
AB  - To determine the prevalence of viral hepatitis infection and hepatitis B virus
      (HBV) molecular characterization, 11,200 blood donors from citizens of Shahrekord
      (a city located in west of Iran) were investigated. Results showed HBsAg-positive
      in 1.78% of persons (n=200), anti-HDV-positive in 3% of HBsAg-positive cases
      (n=6) and anti-HCV-positive in 0.67% of donors (n=76). HBV phylogenetic analysis
      disclosed HBV genotype D, sub-genotype D1, and subtype ayw2. Amino acid mapping
      of the HBV pol region revealed various HBV drug-resistance mutations though
      donors had no antiviral therapy. In conclusion, this study demonstrated notable
      viral hepatitis seroprevalence rate in blood donors in west of Iran.

PMID- 19579700
TI  - Trends in frequency and in vitro antifungal susceptibility patterns of Candida
      isolates from women attending the STD outpatients clinic of a tertiary care
      hospital in Northern Italy during the years 2002-2007.
AB  - Vulvovaginal candidiasis is a common mucosal infection caused by saprophytic and
      opportunistic yeasts belonging to the Candida genus. 518 vaginal swabs, with
      positive fungal culture were collected from unselected women attending the
      Sexually Transmitted Disease clinic of an Italian tertiary care hospital over a
      six year period to determine the pathogen prevalence in vulvovaginal candidiasis
      and to evaluate in vitro the antifungal susceptibilities of yeast recovered by
      Sensititre YeastOne antifungal panel plates according to CLSI document M27-A2.
      The isolates belonging to the genus Candida were 495 (95.5%) with Candida
      albicans percentage equal to 61.2%. Voriconazole was highly active (MIC50 0.008;
      MIC90 0.5 microg/ml), regardless of the species tested. On the contrary,
      fluconazole susceptibility was based upon the species. The intrinsic resistance
      to fluconazole of C. krusei was confirmed.

PMID- 19579702
TI  - Paradoxical immune reconstitution inflammatory syndrome associated with previous
      Cryptococcus neoformans infection in an HIV-positive patient requiring
      neurosurgical intervention.
AB  - Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is
      associated with an exaggerated inflammatory response against an opportunistic
      infection during highly active antiretroviral therapy. The only review on IRIS
      associated with Criptococcus neoformans reported 21 episodes including
      lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and
      cryptococcomas. To our knowledge this is the first report of IRIS associated with
      previous meningeal criptococcal infection which required neurosurgical
      intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst
      formed by exclusion of the temporal horn of the right lateral ventricle. We
      demonstrate that this procedure is possible without complications such as
      cryptococcal dissemination into the peritoneum.

PMID- 19579701
TI  - Sequential transmission and long-term persistence of an HIV strain partially
      resistant to protease inhibitors.
AB  - Transmission of drug-resistant HIV-1 variants has been increasingly documented.
      The most commonly observed resistance-associated mutations are thymidine analogue
      mutations as well as non-nucleoside reverse transcriptase inhibitor mutations. We
      report on a case of secondary transmission of a protease inhibitor (PI) primary
      mutation from an infected untreated subject to his sexual partner. Sequences
      isolated from the 2 patients showed a high level of identity (>99%), both
      carrying the major IAS PI mutation M46I. The latter mutation persisted in the
      bloodstream of the female partner 1 year after its first detection.

PMID- 19579703
TI  - Haemophilus parainfluenzae meningitis in an adult associated with acute otitis
      media.
AB  - A case of Haemophilus parainfluenzae meningitis in a woman with a 3-day history
      of acute otitis media is reported. Her medical history included bladder cancer
      surgery. Unequivocal identification of the isolate was obtained by using
      molecular techniques such as 16S rRNA sequencing besides to conventional culture
      methods. To investigate bacterial virulent traits possibly related to invasive
      properties, in vitro serum resistance of our isolate was analyzed, but it was
      found serum susceptible. Our study demonstrates that H. parainfluenzae can be
      considered an opportunistic pathogen able to cause life-threatening infections
      not only in children but also in patients with underlying conditions.

PMID- 19579704
TI  - Polymerase chain reaction based diagnosis of primary gastric tuberculosis in an
      80-year-old woman: a case report and review of the literature.
AB  - The patient had a two month history of gastrointestinal symptoms. Upper
      gastrointestinal endoscopy disclosed 5 mm nodular lesions were seen in the
      prepyloric area. On pathological examination, two granulomatous lesions were
      detected in biopsy specimen. Ehrlich Ziehl-Neelsen staining and cultures of the
      biopsy material were negative, but polymerase chain reaction (PCR) for
      Mycobacterium tuberculosis complex DNA was positive. Clinical diagnosis of
      primary gastric tuberculosis (PGTb) was supported by positive PCR assay and
      histopathological findings. After antituberculosis treatment, nodular lesions
      were not detected. The diagnosis of PGTb was confirmed definitively by the
      success of treatment and repeated endoscopic examination.

PMID- 19579705
TI  - Visceral leishmaniasis in a patient with common variable immunodeficiency and
      evans syndrome: clinical remarks.
AB  - Visceral Leishmaniasis (VL) is a vector-borne zoonosis endemic in Southern Italy
      whose usual clinical features include fever, splenomegaly, pancytopenia and
      hypergammaglobulinemia. The clinical and biochemical picture may be misleading in
      patients with immunodeficiency diseases hampering the diagnosis. We describe a VL
      case in a patient whose spleen had been removed and who had Common Variable
      Immunodeficiency and Evans syndrome.

PMID- 19579706
TI  - Three atypical pulmonary hydatidosis lesions mimicking bronchial cancer from
      Turkey.
AB  - Hydatid disease is endemic in Turkey. Echinococcus granulosus causes cystic
      echinococcosis mostly in the liver and lung. Although pulmonary hydatid cysts can
      be diagnosed by clinical and radiological findings, atypical or complicated lung
      lesions may be misdiagnosed. In the present study, three cases with hemoptysis
      and atypical lung lesions were diagnosed and treated as lung cancer or
      tuberculosis based on the clinical and laboratory findings along with the imaging
      data and fiberoptic bronchoscopy evaluation. Eventually, pathological examination
      of the bronchoscopic biopsy material confirmed the definitive diagnosis as
      pulmonary hydatidosis. The three patients presented herein emphasize the
      importance of considering pulmonary hydatid disease in the definitive diagnosis
      of atypical lung lesions such as bronchial carcinoma in echinococcosis endemic
      areas.

PMID- 19579707
TI  - Re-writing Popper's philosophy of science for systematics.
AB  - This paper explores the use of Popper's philosophy of science by cladists in
      their battle against evolutionary and numerical taxonomy. Three schools of
      biological systematics fiercely debated each other from the late 1960s:
      evolutionary taxonomy, phenetics or numerical taxonomy, and phylogenetic
      systematics or cladistics. The outcome of that debate was the victory of
      phylogenetic systematics/cladistics over the competing schools of thought. To
      bring about this "cladistic turn" in systematics, the cladists drew heavily on
      the philosopher K.R. Popper in order to dress up phylogenetic systematics as a
      hypothetico-deductivist, indeed falsificationist, research program that would put
      an end to authoritarianism. As the case of the "cladistic revolution"
      demonstrates, scientists who turn to philosophy in defense of a research program
      read philosophers with an agenda in mind. That agenda is likely to distort the
      philosophical picture, as happened to Popper's philosophy of science at the hands
      of cladists.

PMID- 19579708
TI  - The rhetorical construction of Eldredge and Gould's article on the theory of
      punctuated equilibria in 1972.
AB  - This article seeks to show how several rhetorical tools were used and, in fact,
      played a central role in the argumentation advanced by Niles Eldredge and Stephen
      Jay Gould in their 1972 seminal article on the theory of Punctuated Equilibria.
      It is analyzed how Eldredge and Gould proceeded through three steps that,
      sequentially integrated, made their argument compelling. It is shown how they
      made use of analogies, metaphors and other rhetorical tools. It is sustained that
      they began by priming the reader to distrust the current interpretation of the
      fossil record offered by most paleontologists and then, in a second step, they
      used specific visual representations in order to suggest that the competitor
      theory was committed to the idea of an even and slow evolution at a constant
      rate, an image utilized by them as straw man. Finally, it is analyzed how, in
      their third step, Eldredge and Gould made use of several rhetorical arguments to
      present their theory as new for paleontology while, at the same time, placing it
      well inside the frame of the modern synthesis, and how they also managed to
      present their theory as more promising and capable of making predictions for
      future researches than the competitor theory.

PMID- 19579709
TI  - Ernst Haeckel's discovery of Magosphaera planula: a vestige of metazoan origins?
AB  - In September of 1869, while studying sponges off the Norwegian island of Gisoe,
      Ernst Haeckel (1834-1919) discovered a tiny, flagellated ball-shaped organism
      swimming about in his samples. Appearing first to be the planula larva of an
      invertebrate marine animal further observation revealed it to be a colony of
      flagellated cells with a complex life cycle transitioning between multicellular
      and single-cell stages and several distinct forms of protozoa. Haeckel named it
      Magosphaera planula (the "magician's ball") and it eventually assumed a central
      role in his theories of animal evolution, appearing as the modern exemplar of the
      blastaea stage in his gastraea theory of metazoan evolution. Throughout the
      latter half of the nineteenth century and into the twentieth it was an object of
      considerable scientific interest, and yet it was only ever observed by Haeckel
      himself and then only the once. Eventually it faded altogether from scientific
      discussion. This paper traces the rise and fall of Magosphaera as an important
      epistemic object in the theories of Haeckel and other biologists, and an attempt
      is made to identify what exactly the organism (or organisms!) was that Haeckel
      observed in the fall of 1869.

PMID- 19579710
TI  - Hopeful heretic--Richard Goldschmidt's genetic metaphors.
AB  - Richard Goldschmidt famously rejected the notion of atomic and corpuscular genes,
      arranged on the chromosome like beads-on-a-string. I provide an exegesis of
      Goldschmidt's intuition by analyzing his repeated and extensive use of
      metaphorical language and analogies in his attempts to convey his notion of the
      nature of the genetic material and specifically the significance of chromosomal
      pattern. The paper concentrates on Goldschmidt's use of metaphors in publications
      spanning 1940-1955.

PMID- 19579711
TI  - Hybridizing bacteria, crossing methods, cross-checking arguments: the transition
      from episomes to plasmids (1961-1969).
AB  - Plasmids are non-chromosomal hereditary determinants, mostly found in
      prokaryotes. Whereas Joshua Lederberg coined the term "plasmid" as early as 1952,
      today's concept was not established until the early 1970s. In this eclipse
      period, the plasmid's place was taken by the episome, following the 1958
      publication of Elie Wollman and Francois Jacob. This paper analyzes the
      transition from the episome to a renewed plasmid concept both on the experimental
      and the conceptual level. It will become clear that intergeneric transfer
      experiments were central to this development. These studies rely on conjugational
      transfer of extrachromosomal hereditary determinants between different bacterial
      genera. First, experimental systems employing intergeneric transfer shaped the
      new plasmid by enabling its representation as a species of circular DNA.
      Moreover, they had a destabilizing effect on the episome, leading to a crisis in
      the concepts of microbial genetics towards the end of the 1960s. The new plasmid
      then became one of the cornerstones of recombinant DNA technologies. In an
      historic perspective, intergeneric transfer experiments indicate a gradual
      transition of molecular biology from its early "analytic" to the "synthetic"
      phase of genetic engineering. Hence, the construction of genetic hybrids in vivo
      as epitomized in the studies shown here marks an intermediate state that one
      could designate as "recombinant DNA avant la lettre".

PMID- 19579712
TI  - The under-recognized implications of heterogeneity: opportunities for fresh views
      on scientific, philosophical, and social debates about heritability.
AB  - Despite a long history of debates about the heritability of human traits by
      researchers and other critical commentators, the possible heterogeneity of
      genetic and environmental factors that underlie patterns in observed traits has
      not been recognized as a significant conceptual and methodological issue. This
      article is structured to stimulate a wide range of readers to pursue diverse
      implications of underlying heterogeneity and of its absence from previous
      debates. Section 1, a condensed critique of previous conceptualizations and
      interpretations of heritability studies, consists of three core propositions
      centered on heterogeneity and six supplementary propositions. Reference is made
      to agricultural evaluation trials in which a number of different genetically
      replicable varieties are raised in multiple replicates in one or more locations.
      In such analyses, the best case for illuminating genetic and environmental
      factors can be achieved; analyses in human genetics, in contrast, fall far short
      of the ideal. Section 2 identifies a wide range of questions that invite
      philosophical, historical, sociological, and scientific inquiry. These are
      organized under four headings: debate over the conceptual implications of
      heterogeneity; history of translation of methods from agriculture and laboratory
      breeding into human genetic analysis; racialized imaginaries in the analysis of
      differences among groups; and areas of scientific inquiry that may allow more
      attention to underlying heterogeneity.

PMID- 19579713
TI  - Eradicating polio: it's feasibility in near future?
AB  - Continuous wild poliovirus transmission despite 12 years of intensive
      surveillance has raised serious questions about the feasibility of polio
      eradication programme with current strategy in near future. At present most of
      the cases are confined to four endemic countries, which are causing sporadic
      outbreaks in non-endemic areas. India has experienced a significant increase in
      number of cases reported in 2006 compared to previous year. Outbreaks originated
      in western UP which was due to the accumulation of susceptibles between the last
      outbreak in 2002 and early 2006. Substantial improvement has been observed in
      strategies of polio eradication but still there are gaps in the programme
      implementation which needs immediate attention so that goal of polio eradication
      can be achieved at the earliest opportunity. Even though there are many issues
      but there are also many factors, which favour polio eradication. These factors
      include new tool in form of m OPV, natural immunity due to recent outbreak,
      limiting international spread of polio, new researches to guide programme in
      right direction, political commitments from endemic countries, etc. 2008 presents
      the best opportunity ever to interrupt wild polio virus transmission which will
      lead to global eradication of Polio. Since global eradication is within sight, it
      is scientifically possible to eradicate the disease in near future.

PMID- 19579714
TI  - Avian influenza: current scenario.
AB  - Avian influenza commonly called as 'Bird flu' is a matter of great concern which
      has caused three major pandemics in twentieth century killing millions of people.
      Recent epidemic with H5N1 type strain started in 1997 and is still continuing.
      Disease has assumed new proportions since its confirmed association with
      migratory birds. In India also, three separate outbreaks have been announced till
      now by Government of India. This virus has tremendous capacity for gene
      reassortment and humans by enlarge do not have any immunity against them. This
      fact has raised global fears of an imminent influenza pandemic. The neuraminidase
      inhibitors currently are the only drugs which can be used, in case pandemic
      occurs. Therefore, timely development of an effective influenza vaccine is must
      and should be made a public health priority.

PMID- 19579715
TI  - The 2006 dengue outbreak in Delhi, India.
AB  - Dengue is a worldwide condition spread throughout the tropical and subtropical
      zones between 30 degrees north and 40 degrees south. It is endemic in South East
      Asia, the pacific, East and West Africa, the Caribbean and the Americas. Dengue
      outbreaks are occurring almost every three yearly in Delhi for the last 12 years.
      The latest outbreak was in the year 2006, which started late in August, peaked in
      the month of October and lasted till late November. We describe here the
      clinical, hematological and biochemical data of 70 patients of dengue fever
      diagnosed as per WHO criteria in Lok Nayak Hospital, New Delhi during this
      outbreak. Hematological parameters were estimated by automated counter and dengue
      serology was done by capture ELISA technique. The results displayed widespread
      effect of dengue fever on hematological and biochemical profile. Some of our
      patients also had atypical dengue manifestations. These results suggest that
      dengue fever is a major public health problem which can lead to significant
      morbidity and can even be fatal at times. All efforts should be made to prevent
      it.

PMID- 19579716
TI  - Investigation of viral hepatitis E outbreak in a town in Haryana.
AB  - An outbreak of 160 cases of viral hepatitis which occurred in Shahbad, Haryana,
      was investigated to ascertain the agent, cause of the outbreak and to initiate
      remedial measures. Out of the 30 samples tested, 26 (86.7%) were positive for IgM
      antibody against HEV, establishing hepatitis E virus responsible for the
      outbreak. Significant association of higher attack rates (4%) in ward 14 (OR =
      17.9; 95% CI = 12.7-25.2) of the town along with leakage in water distribution
      system running co-existent with open drains containing household waste and
      sewage; and absence of residual chlorine in water samples tested at household
      level in ward 14 established fecal contamination of water as the cause of the
      outbreak. Remedial repair work was initiated along with superchlorination of
      water which contained the outbreak.

PMID- 19579717
TI  - Evaluation of Tribulus terrestris Linn (Zygophyllaceae) acetone extract for
      larvicidal and repellence activity against mosquito vectors.
AB  - Acetone extracts of leaves and seeds from the Tribulus terrestris
      (Zygophyllaceae) were tested against mature and immature different mosquito
      vectors under laboratory condition. The extract showed strong larvicidal,
      properties 100 per cent mortality in the 3rd-instar larvae was observed in the
      bioassays with An. culicifacies Giles species A, An. stephensi Liston, Culex
      quinquefasciatus Say and Aedes aegypti Linn, against 200 ppm of the leaf acetone
      extract and 100 ppm seed acetone extract. The LC50 values of leaf acetone extract
      estimated for 3rd-instars An. culicifacies species A, An. stephensi, Cx.
      quinquefasciatus and Ae. aegypti after 24 hour of exposure were 117, 124, 168 and
      185 ppm respectively. The LC50 values of seed acetone extract estimated for 3rd
      instars An. culicifacies species A, An. stephensi, Cx. quinquefasciatus and Ae.
      aegypti after 24 hour of exposure were 100, 72, 91 and 91 ppm respectively. It is
      confirmed from the LC50 values that the seed acetone extract of T. terrestris is
      more effective compared to leaf extracts. A significant (P<0.004) higher
      concentration of acetone extract leaf was required to kill equal number of larvae
      i.e. against acetone extract of seed. The seed acetone extract showed strong
      repellent activity against adults mosquitoes. Per cent protection obtained
      against Anopheles culicifacies species A 100% repellency in 1 h, 6 h; Anopheles
      stephensi 100% repellency in 0 h, 4 h, 6 h; and Culex quinquefasciatus 100%
      repellency in 0 h, 2 h, 4 h, at 10% concentration respectively. Against Deet-
      2.5% An. culicifacies Giles species A has shown 100% repellency in 1 h, 2 h, 6 h,
      An. stephensi Liston 99% repellency in 4 h, and Culex quinquefasciatus Say has
      shown 100% repellency in 1 h, 2 h.

PMID- 19579718
TI  - Effect of synergist piperonyl butoxide (PBO) on the toxicity of some essential
      oils against mosquito larvae.
AB  - Effect of a known synergist piperonyl butoxide on the toxicity of steam
      distillate essential oils of Jamarosa (Cymbopogan nardus), Pacholli (Pogostemon
      pacholli), Basil (Ocimum basilicum), and Peppermint (Mentha pipreta) plant
      species against Anopheles stephensi larvae were evaluated. The purpose of the
      present study was to identify the insecticidal potential of these oils against
      mosquito larvae. The Piperonyl Butoxide (PBO) was used to enhance the activity of
      these oils with the aim of developing essential oil based formulations. The
      bioassays of these oils with and without PBO were performed against late 3rd
      instar larvae of An. stephensi. The LC50 values against An. stephensi were 44.19
      ppm for Ocimum basilicum oil, followed by, Mentha pipreta, Cymbopogan nardus, and
      Pogostemon pacholli oil which gave LC50 values above 250 ppm. Thus in the present
      study the Ocimum basilicum oil was found to be most effective, whereas Pogostemon
      pacholli oil was found to least effective against mosquitoes for larvicidal
      action. The effect of synergist PBO led to the enhancement of toxicity of oils,
      the LC50 value for Ocimum basilicum were reduced from 44.19 ppm to 23.87 ppm.
      Similarly the oil of Pogostemon pacholli showed most significant results where
      the LC50 value was >250 ppm it was reduced to 50 ppm with PBO.

PMID- 19579719
TI  - Prevalence of extended spectrum beta-lactamases producing clinical isolates from
      patients of urinary tract infection in a tertiary care hospital in Delhi.
AB  - A total of 250 urinary isolates (188 Escherichia coli and 62 Klebsiella
      pneumoniae) were studied for ESBL production by double disc approximation test
      and disc diffusion confirmatory test (NCCLS). ESBL production was found to be 56%
      in E. coli and 52% in K. pneumoniae. The double disc approximation test showed
      false ESBL production in five (2.6%) isolates of E. coli and one (1.6%) K.
      pneumoniae. The susceptibility of ESBL producers to imipenem, amikacin,
      nitrofurantion was found to be 100%, 86% and 84% respectively. A high degree of
      co-resistance to co- trimaxazole and norfloxacin was found in strains of ESBL
      producers. Seventy five per cent of ESBL producers detected were from
      hospitalized patients admitted in ICU or undergoing surgery.

PMID- 19579720
TI  - Clinical and laboratory comparison of different brands of amphotericin B used for
      the treatment of Kala-azar: an observational study.
AB  - The communication presents clinical response of cases of visceral leishmaniasis
      to treatment by two different brands of Amphotericin B. Fungizone was found to be
      slightly better than Amphotericin B, however, the difference is not statistically
      significant.

PMID- 19579721
TI  - Leprosy scenario in Agra: epidemiological observations from rapid population
      survey 2004-06.
AB  - This study based on rapid survey methodology examining 17.86 lakhs population
      revealed that leprosy prevalence in Agra District is 6.1/10,000 during 2004-06,
      with 97.2% of the cases detected for the first time. Although leprosy is still
      endemic but all the leprosy indicators have shown positive change since last
      survey in 2001-03. The results seem promising to achieve elimination target
      (<1/10,000) since prevalence/10,000 population declined from 16.4 in 2001-03 to
      6.1 in 2004-06, MB rate from 22.3 to 17.1, Mean duration of disease at detection
      (months) from 32.3 to 22.9, per cent new cases increased from 88.2% to 97.2% and
      visible disability (Grade > or = 2) rate declined from 4.8% to 2.36% over this
      period. The data on patients with incomplete history of treatment (prevalent) but
      having active disease indicate that only about 3% (31/1090) had approached the
      health center for treatment. Of these 31 patients, 29% defaulted from treatment
      and still have active disease and 75.2% (23/31) had MB disease indicating a
      pattern of late reporting to health system. This study suggests that repeat
      surveys are useful to detect cases for treatment and seems the key to achieve
      leprosy elimination or even eradication at district level in all endemic
      districts.

PMID- 19579722
TI  - Do colour and surface area of ovitrap influence the oviposition behaviour of
      Aedes aegypti, the vector of dengue and DHF?
AB  - A newly developed ovitrap made from a fiberglass tray (FGTO) was compared with
      conventionally used black jar ovitrap (BJO) in field condition in terms of number
      of eggs received. The number of eggs laid in FGTO was consistently higher than in
      BJO. The number of eggs collected in FGTO was significantly higher and it was 5
      94 times more than that of BJO (t =9.45; p<0.0001). This finding has implication
      in designing lethal ovitraps for the control of dengue vectors.

PMID- 19579723
TI  - Profiles of HIV positive attendees in the Voluntary Counseling and Testing Centre
      in Nainital District of Uttarakahand.

PMID- 19579724
TI  - Awareness status about HIV/AIDS among Indian railway's employees and their family
      members.
AB  - A house to house survey was conducted in December 2005 in the Railway Colony of
      Shamli, located in the state of Uttar Pradesh, India using a semistructured
      questionnaire to study the awareness level regarding HIV/AIDS among Indian
      Railway's employees and their family members. Information regarding demographic
      characteristics and knowledge about various aspects of HIV/AIDS was recorded by a
      trained staff nurse of the local Railway Medical Unit from at least one person,
      aged 15 years to 59 years, from each household. Among 293 individuals
      interviewed, majority were males (61.8%), aged > 30 years (56.6%) and literate
      (85.3%). Majority were aware about existence of HIV infection in India (92.5%),
      AIDS is a fatal disease (92.8%) and laboratory tests are available for detecting
      HIV infection (89.4%). Although most of them knew the correct routes of HIV
      transmission viz. sexual (91.50%), parentral (90.8%), perinatal route (86.3%) and
      blood transfusion (86.0%), misconceptions such as transmission through shaking
      hands (89.1%), hugging (88.4%), sharing utensils (82.6%), mosquito bite (74.1%)
      and using public toilets (73.4%) were also observed. Most of them were also aware
      about preventive measures. Knowledge about various aspects was observed to be
      significantly higher among females, among individuals aged <45 years and literate
      individuals. The findings highlight the need of intensified health education
      focusing on removal of misconceptions and further improvement in awareness level
      of the study population.

PMID- 19579725
TI  - Infectious diseases in children-still leads.

PMID- 19579726
TI  - Outcomes of primary percutaneous coronary intervention (PCI) in a tertiary care
      cardiac centre.
AB  - OBJECTIVE: To determine the outcomes of primary percutaneous coronary
      intervention (PCI) in a tertiary care cardiac centre. METHODS: Medical records of
      104 consecutive patients presented in our hospital between January 2006 to
      December 2007 with acute ST elevation myocardial infarction (STEMI) and treated
      with primary PCI as a mode of reperfusion were reviewed. The primary end point
      was in hospital mortality and secondary end points were 30 day mortality,
      myocardial infarction, recurrent angina and congestive cardiac failure, from
      discharge to one month follow up. RESULTS: The procedural success was 97%. Six
      (5.8%) patients died during hospital stay including one on table death. Out of
      six patients who died, five (83.3%) had cardiogenic shock. No mortality was
      observed in the 30 days follow up from discharge while other complications like
      myocardial infarction, recurrent angina and congestive cardiac failure were 1%,
      1% and 5% respectively. CONCLUSIONS: Our findings suggest that favourable
      outcomes, matching the international data can be achieved in our patients with
      primary PCI in the management of life threatening illness like STEMI despite all
      the limitations. Primary PCI as a preferred method of reperfusion strategy fieeds
      to be practiced more often in our part of the world.

PMID- 19579727
TI  - Non-conventional transmission of hepatitis C: a true possibility ignored.
AB  - OBJECTIVE: The exact mode of hepatitis C virus (HCV) transfer remains elusive in
      a vast majority of cases. We examined the possibility of non-conventional
      transmission of HCV by person-to-person contact. METHOD: A questionnaire based,
      prospective study was conducted at Pakistan Institute of Medical Sciences (PIMS)
      from July-October, 2006. Patients with compensated chronic hepatitis B (CHB) &/or
      C (CHC) were registered for 6 month interferon (IFN) therapy. All candidates
      furnished information about age, gender and mode of transmission. The unanswered
      queries were interpreted as "missing data". After omission of cases with
      hepatitis B virus (HBV) infection alone, the remaining persons included in the
      present study were placed in: Group-A: Multifactorial transfer involving
      conventional (blood borne) and non-conventional modes; Group-B: Unifactorial
      transfer by non-conventional routes only; Group-C: No identifiable risk factor.
      Unlike conventional routes, the non-conventional modes represented likelihood of
      CHB &/or CHC by exposure to household contacts, to persons with hepatic cirrhosis
      and during traveling. RESULTS: Initially, 879 patients (mean age: 35.52 +/- 9.1
      years) were registered. After exclusion of 25 subjects with HBV infection only,
      the remaining 854 were included. Of 854 cases, 830 (97.18%) were infected with
      HCV and 24 (2.81%) had co-infection with HBV & HCV. According to the mode(s) of
      transmission, Group-A: 515 (60.30%); Group-B: 136 (15.92%) and Group-C: 203
      (23.77%) cases were identified. Dental treatment: 278 (32.55%) was the commonest
      conventional risk factor in Group-A. The non-conventional transfer of HCV in
      Group-A was mainly suggested by household contact: 222 (25.99%). Groups-A and -B
      combined, the sum of any non-conventional risk factor was comparable with and
      even higher than the leading haematogenous routes in Group-A. Groups-B and -C
      combined, HCV infection in 339 patients (39.69%) was apparently acquired by non
      conventional modes, most probably by person-to-person interaction. CONCLUSION:
      Non-conventional transmission of HCV is a genuine possibility which is currently
      underestimated.

PMID- 19579728
TI  - Prevalence of hepatitis D in HBsAg positive patients visiting liver clinics.
AB  - OBJECTIVE: To estimate the prevalence of hepatitis D in HBsAg (hepatitis B
      surface antigen) positive patients visiting liver clinics. METHODOLOGY: All HbsAg
      positive patients who had visited two liver clinics; in Karachi and in Jacobabad,
      from October 2007 to March 2008, were included in this study. These patients were
      tested for HBV DNA and HDV RNA by PCR technique, HBeAg and anti-HDV. Clinical
      status of the patients was evaluated by examination, routine biochemical tests
      and ultrasound. RESULTS: Total numbers of patients included in the study were 362
      comprising of 151 patients from the clinic in Jacobabad and 211 from Karachi. The
      patients ranged from 4 to 70 years age (mean age 29.75 +/- 11.27). Out of the
      total patients 297 (82%) were males. All the patients were screened for HDV
      antibody out of which 212 (58.6%) tested positive. Total 65 anti-HDV positive
      patients were tested for the HDV RNA by PCR, out of which 30 (46.2%) tested
      positive for the virus. Three hundred and forty (340) patients were screened for
      HBeAg, out of which 71 (20.9%) tested positive. Three hundred and seven patients
      were screened for HBV DNA by PCR, out of which 88 (28.7%) were positive for the
      virus. HBV DNA was positive in 16.2% of HbeAg negative patients (pre-core
      mutants). The frequency of positive HDV antibody was 69.23% in patients from
      Kashmore, 67% in Jacobabad, 65.4% in Jaffarabad, 65.21% in Quetta, 60% in
      Naseerabad, 36.58% in Karachi, 58.33% in other areas of Balochistan and 60.71% in
      other areas of Sindh. Positive HDV antibody status was associated with more
      severe and advanced disease (p < 0.0001). CONCLUSION: This data shows extremely
      high prevalence of hepatitis D in the referred patients from some areas of
      Southern Pakistan. Effective preventive measures are the need of the hour and
      Pakistan may be considered as one of the areas of highest HDV prevalence around
      the globe.

PMID- 19579729
TI  - Palliative management of irresectable carcinoma esophagus using self expandable
      metallic stent (SEMS).
AB  - OBJECTIVE: To evaluate the symptomatic relief of dysphagia after stenting in
      patients with carcinoma esophagus METHODS: A prospective non randomized
      descriptive study was conducted at Surgical Unit 4, Civil Hospital Karachi,
      Pakistan over a period of 1 year, from August 2006 to July 2007. A total of 41
      patients with biopsy proven carcinoma esophagus having irresectable disease on
      the basis of CT scan or poor risk for major surgery were included in the study.
      Self expandable metallic stents were placed under fluoroscopic guidance in all
      the patients. Follow up was done weekly for 1 month and monthly for 6 months or
      till death of the patient. Data was analyzed using SPSS version 11. RESULTS: Age
      of the study population ranged from 25-80 years with mean age of 51.49 +/- 14.25
      years. Male to female ratio was 1.15:1. Preoperative dysphagia for solids was
      seen in 4.9%, for semi solids in 31.7%, and for liquids in 63.4%. 80.5% of
      patients had squamous cell carcinoma and 19.5% of patients had adenocarcinoma.
      Dilatation prior to stenting was done up to 12.8 mm in 65.9%. Complete relief of
      dysphagia was seen in 73%. No procedure related mortality was seen in our study.
      Overall complication rate was 29.2%. CONCLUSION: SEMS is an effective method for
      the relief of dysphagia in patients with irresectable carcinoma esophagus.

PMID- 19579730
TI  - Pakistan: the new target of terrorism. Are Karachi's emergency medical response
      systems adequately prepared?
AB  - OBJECTIVE: To assess the efficacy and preparedness of the pre-hospital and
      hospital emergency medical systems and post graduate trainees in the city to deal
      with a massive terrorist strike. METHODS: A cross-sectional survey of
      postgraduate trainees was conducted at Jinnah Postgraduate Medical Center and
      Civil Hospital Karachi from 21st July 2007 to 24th July 2007, to evaluate the
      preparedness and self identified deficiencies of doctors involved in massive
      trauma casualty management. To assess the pre-hospital care in Karachi,
      structured telephonic interviews were conducted of administrators of two private
      run charity based ambulance services. RESULTS: Out of the 90 respondents
      questioned regarding a self assessment of their training, only 3 (3.3%) of them
      were confident about their management of bomb blast victims. Eighty-seven (96.6%)
      of the respondents felt they required some further training (44.4%) or
      comprehensive training (52.2%). No simulated drills or courses had been conducted
      for disaster management in the emergency department of the surveyed Hospitals.
      Most of the ambulance drivers had no paramedic training. Ambulances are equipped
      with a stretcher and an oxygen cylinder only. No resuscitation measures are
      available in the ambulances. CONCLUSION: With an increasing number of terrorist
      attacks in the country, massive influx of casualties in a relatively short time
      span has become a regular feature of the Pakistani hospital system. Lack of
      adequate training at pre-hospital and in hospital levels may translate into
      increasing morbidities and mortalities. It is imperative that training of junior
      doctors and paramedical staff be conducted regularly and an effective regional
      communication base established for efficient interdepartmental coordination.

PMID- 19579731
TI  - Anaesthesia at remote location: use of modified Bain circuit (Mapleson D) at
      Kunri Christian Hospital (KCH).
AB  - OBJECTIVE: To develop a safe general anaesthesia technique for remote areas with
      lack of facilities. METHODS: Four types of anaesthesia techniques using TIVA and
      modified Bain circuit were planned. Monitoring facility was limited to manual
      sphygmomanometer, palpation of radial pulse and monitoring of colour of skin and
      blood. Depth of anaesthesia was assessed using EVANs, RPST scoring system.
      Patients were asked in recovery room for awareness. RESULTS: Surgeries done were
      cesarean sections, laparotomies, gynaecological, urological, hernia and burn
      contractures. Six patients had RPST score of 5 or more and three patients in
      recovery room complained of awareness. Cost per Anaesthesia was Rs225.
      CONCLUSION: TIVA with modified Bain circuit provided effective anaesthesia in
      remote area at low cost.

PMID- 19579732
TI  - Community acquired pneumonia: risk factors associated with mortality in a
      tertiary care hospitalized patients.
AB  - OBJECTIVE: To evaluate risk factors associated with mortality in patients
      hospitalized with CommunityAcquired Pneumonia (CAP) from a developing country.
      METHODS: An observational study was conducted on adult patients admitted with a
      diagnosis of CAP from January 2002 to August 2003 at Aga Khan University
      hospital, Karachi, Pakistan. Clinical records were reviewed for demographic
      characteristics, clinical and laboratory features, hospital course, and risk
      factors associated with mortality. RESULTS: A total of 329 patients (187 males)
      were admitted with CAP. Two-third of patients had underlying co-morbid medical
      illnesses. Complications developed in 15.7% cases and the overall mortality rate
      was 11%. Risk factors were identified on initial clinical assessment, laboratory
      and radiological features and during hospital course. On admission elevated blood
      urea, new onset of confusion, abnormal liver function test, low serum albumin,
      cardiomegaly and presence of underlying malignancy were strongly associated with
      increased mortality. Failure to respond to therapy was associated with a high
      risk of mortality as depicted by complication during hospital stay (Odds Ratio =
      23.3, 95% Confidence Interval = 10.3-52.8), need for mechanical ventilation (OR =
      17.1, 95% CI = 7.4-39.8) and need for intensive care unit (OR = 9, 95% CI = 4.2
      19.3). CONCLUSIONS: Abnormal liver function test, low albumin and presence of
      cardiomegaly were more significant mortality risk factors than age, respiratory
      rate and blood pressure. Elevated blood urea and confusion remain strong risk
      factors on admission. Failure of response to therapy and onset of complications
      heralded a high risk of death.

PMID- 19579733
TI  - Evaluate the outcome and identify predictive failure of outpatient laparoscopic
      cholecystectomy.
AB  - OBJECTIVE: To evaluate the outcome of undertaking out-patient laparoscopic
      cholecystectomy (OLC) and identifying its predictive failures. METHODS: One
      hundred and forty-nine consecutive patients with symptomatic cholelithiasis
      scheduled for preplanned elective laparoscopic cholecystectomy (LC) from August
      2004 to December 2006 were included in the study. Patients with associated severe
      diseases, ASA class III and IV who would have required post operative surgical
      care, residents of remote areas and other surgical reasoning were entered in
      Inpatient's Laparoscopic Cholecystectomy (ILC) group (n = 57) and others were
      enrolled in OLC group (n = 87). Five patients converted to open surgery and thus
      were excluded from the study. All patients were recruited during the initial
      outpatient visit and the full preoperative details were explained to them. All of
      the related factors of OLC were recorded in every visit. Significant differences
      were evaluated using Chi-square and fisher exact test. RESULTS: Eighty seven
      patients (58.3%) were selected for outpatient group from which 69 patients
      (79.3%) successfully underwent outpatient LC. Eighteen (20.7%) patients (failure
      rate) were not discharged at all. Comparing successful and unsuccessful OLC, the
      mean age was 41.1 +/- 12.7 vs 51.3 +/- 16.1 years (P = 0.005), also the mean
      operation time was 33.7 +/- 13.3 vs 33.1 +/- 13.8 minutes and the ability for
      oral intake existed in 66 patients (95.7%) vs 15 patients (83.3%) (P = 0.1)
      respectively. Pain was the most common cause of failure of OLC. CONCLUSIONS: OLC
      is safe and feasible with low readmission. It achieves high levels of patient
      satisfaction and acceptance, when patients are carefully selected. A prospective
      study with a larger sample size should be warranted to verify whether OLC can be
      useful for high age and high ASA class patients.

PMID- 19579734
TI  - Reasons of conversion of laparoscopic to open cholecystectomy in a tertiary care
      institution.
AB  - OBJECTIVE: To determine the frequency and reasons of conversion of laparoscopic
      cholecystectomy (LC) to open cholecystectomy (OC) in a tertiary care teaching
      hospital. METHODS: A prospective analysis of conversion of laparoscopic to OC was
      performed in one Surgical Unit of Civil Hospital Karachi, from 1st September 1997
      to 31st May 2005. There were 1238 patients in the series. The inclusion criteria
      were: all patients with symptomatic cholelithiasis, who were subjected to LC. The
      exclusion criteria were: cases with incomplete laboratory or histopathology data,
      patients who were lost to follow-up, and patients with preoperative diagnosis of
      carcinoma of gallbladder. RESULTS: Eighty-one (6.5%) patients were converted to
      OC, due to difficult anatomy, complication or equipment failure. The frequency
      during learning curve was 9% vs. 6.3% during skill curve. The conversion rate was
      higher in male patients (16.45% males vs. 5.09% females), and in patients with
      acute cholecystitis (24.39% acute vs. 5.06% chronic). In eight cases, conversion
      was due to major complication: bleeding (6), and bowel injury (2). In 73 cases,
      conversion was carried out electively; disturbed anatomy at Calot's triangle
      (44), wide cystic duct (7), choledocholithiasis (5), dense adhesions between
      gallbladder and bowel (4), biliodigestive fistula (1), and equipment failure
      (12). CONCLUSION: The overall frequency of conversion of LC to OC was 6.5%; the
      risk was more during the learning curve, in male patients and in patients with
      acute cholecystitis.

PMID- 19579735
TI  - Three consecutive audits to achieve acceptable colonoscopy completion rates.
AB  - OBJECTIVE: To compare the acceptable colonoscopy completion rates in three
      successive audits, identifying the reasons for failure of completion and
      rectifying them to improve the performance at our endoscopy unit. METHODS: Study
      was conducted at Endoscopy unit of Medical Unit One Civil Hospital Karachi. The
      first audit was conducted retrospectively on the colonoscopy results, done from
      November 2004 to November 2005. As the information was incomplete, a performa was
      designed for the next prospective audit from December 2005 to November 2006. The
      shortcomings found in the results of this audit were improved in the third audit
      done prospectively from December 2006 to November 2007. RESULTS: In the first
      audit 164 patients (111 male) underwent colonoscopy. The mean age was 40 +/-
      10.08 years. The overall caecal intubation rate was 55%, but adjusted caecal
      intubation was not calculated because of inadequate documentation. In the second
      audit, 119 patients (66 male) underwent colonoscopy. The mean age was 45 +/-
      10.17 years. After implementing changes the overall crude caecal intubation rate
      was 54.8% and the adjusted caecal intubation rate was 75% with exclusion of
      strictures and poor preparation. In the third audit, 122 patients (58 males)
      underwent colonoscopy. The mean age was 38 +/- 11.07 years. With further
      improvement in methodology the overall crude caecal intubation rate was (80.3%)
      and the adjusted caecal intubation rate was (98%). CONCLUSION: These audits
      allowed us to evaluate our endoscopy services and to detect the short comings and
      deviation from standard techniques and hence improving the performance in the
      subsequent year for the benefit of patients.

PMID- 19579736
TI  - Adult onset Stills disease in a tertiary care hospital of Pakistan.
AB  - OBJECTIVE: To study the clinical characteristics of Stills disease in a tertiary
      care hospital of Pakistan and compare it with similar published studies.
      MATERIALS AND METHODS: (Retrospective descriptive study) Thirteen patients with
      Adult onset stills disease were identified by chart review of last ten years from
      1995 to 2005 at Aga Khan University Hospital (AKU), a tertiary care private
      medical university in Karachi Pakistan. Demographic and other specific
      information was recorded on standardized data sheet and analyzed by SPSS 11.5
      software. RESULTS: Mean age of patients was 26.54 +/- 10.34 years, of which 8
      (61.5%) were males. The most common presenting features were fever (100%),
      arthralgias and myalgias (100%) with large joint involvement (91.7%), significant
      weight loss (30.8%), sore throat (53.8%). None of the patients had skin rashes
      with fever, chest and abdominal pains. One patient had cervical lymph node
      swelling and 4 (33.3%) patients had splenomegally. The common laboratory findings
      were: leukocytosis and anaemia (100%), elevated ESR and C reactive protein
      (100%). Thrombocytosis (56.2%) and elevated Liver function tests (62%). Seven
      patients had serum ferritin checked which was in the range of 1872 to 16652 iu/l.
      None of the patients had positive ANA, Anti-DNA or RA factor. Twelve patients had
      a chest x-ray done, among them 11 were normal, one had pleural effusion. The
      clinical course of the patients who were followed for three months, was
      monocyclic (53.8%), polycyclic (30.8%) and persistent (15.4%). CONCLUSION:
      Clinical characteristics of Stills disease in our country are mostly similar to
      those seen in other regions, suggesting that same pathogenetic factors may be
      implicated in patients from different genetic back grounds and geographic
      locations.

PMID- 19579737
TI  - Timing of umbilical cord clamping and neonatal haematological status.
AB  - OBJECTIVES: To determine the effect of delayed umbilical cord clamping on Hb
      (haemoglobin) and bilirubin levels of neonates and to identify newborn babies
      with anaemia and refer them for treatment. METHODS: This Randomized Controlled
      Trial was conducted in the Department of Obstetrics and Gynaecology, Unit V, Dow
      Medical College and Lyari General Hospital and Department of Pathology, Lyari
      General Hospital, between 1st November, 2006 and 15th July, 2007. Patients
      admitted to labour ward were selected according to inclusion criteria of the
      study. They were randomly allocated to 2 groups. Group A included women in whom
      umbilical cord was clamped immediately after birth. In Group B, clamping was
      delayed until cessation of pulsations in the cord. After cutting the cord, sample
      of blood was collected from the cut end of cord of the newborn for Hb and
      bilirubin. After 6 hours of birth, another sample of blood was drawn from
      antecubital vein for serum bilirubin. Samples were sent to laboratory for
      analysis. All data were entered and analyzed using SPSS version 11. RESULTS: Two
      hundred women were studied, 100 in each of the 2 groups. Mean maternal Hb was
      9.75 g/dl in Group A and 9.95 g/dl in Group B. The average neonatal Hb was 14.1
      g/dl in Group A and 15.2 g/dl in Group B (p = 0.008). In all 49% neonates in
      Group A and 37% in Group B had Hb < 14 g/dl. Serum bilirubin values at birth and
      at 6 hours of birth were 1.8 mg/dl and 2.5 mg/dl for Group A and 1.9 mg/dl and
      2.7 mg/dl for Group B, respectively. The difference in bilirubin after 6 hours in
      the 2 groups was insignificant (p = 0.186). CONCLUSION: Delayed umbilical cord
      clamping at birth seems to be safe and can be expected to reduce the prevalence
      of anaemic newborn babies in our community.

PMID- 19579738
TI  - The predictive value of ultrasound assessment of amniotic fluid index,
      biophysical profile score, nonstress test and foetal movement chart for meconium
      stained amniotic fluid in prolonged pregnancies.
AB  - OBJECTIVE: To evaluate the value of non-stress test (NST), biophysical profile
      score (BPS), amniotic fluid index (AFI) and foetal movement charted (FMC) by
      mother in the prediction of meconium passage in post-date pregnancies. METHODS:
      In a cross-sectional study performed from 2003 to 2005, in the Ali-Ebne-Abitaleb
      Hospital, all post-date singleton pregnant women were included and evaluated a
      few hours before delivery for AFI, NST, BPS and FMC. Based on the results of the
      mentioned tests the occurrence of foetal distress was foreseen and the judgments
      were compared with the results of evaluation of the amniotic fluid after
      amniotomy during labour. Our judgment of occurrence of foetal distress was based
      on meconium staining of amniotic fluid (MSAF) as the gold standard. RESULTS: In
      this study 250 women were included. The sensitivity and specificity of these
      tests respectively were: 62% and 42% for NST, 66% and 56% for BPS, 38% and 83%
      for AFI and 44% and 64% for FMC. The highest positive predictive value was
      recorded respectively for AFI (52%) and negative predictive value was recorded
      for NST (94%). There was a significant association between MSAF and BPS. In
      univariate analyses, there was a significant association between MSAF and BPS (P
      = 0.010 for linear by linear association, exact method). Also there was a
      significant association between MSAF and AFI < 5 cm. (OR = 2.99, 95% CI, 1.57
      5.74). CONCLUSION: Although BPS and AFI had the highest level of prediction, they
      are of limited usefulness in prediction of foetal distress. The reactive NST is
      more conclusive.

PMID- 19579739
TI  - Knowledge, attitude and preventive practices for breast cancer among health care
      professionals at Aga Khan Hospital Karachi.
AB  - OBJECTIVE: To assess the knowledge and practice of risk factors, symptoms and
      screening for breast cancer among health care professionals. METHODS: A cross
      sectional study was carried out at The Aga Khan University Hospital from January
      2008 to March 2008. A total of 336 health care workers including consultants
      (48), fellows (17), residents (76), medical officers (14), interns (37), nurses
      (94) and fourth and final year medical students (50) were requested to fill a
      questionnaire designed to assess the knowledge about the risk factors, signs and
      symptoms, screening tools, breast self examination (BSE) and treatment. RESULTS:
      More than two third participants had good knowledge about the risk factors and
      signs of breast cancer except some dissociation regarding association of menarche
      status and smoking. Majority was aware of the benefits of mammography. More than
      80% had the consensus that breast cancer is curable if detected early and more
      than 50% thought that a surgeon should be consulted first if lump is palpable.
      CONCLUSIONS: This study reveals that health care professionals have fairly good
      awareness regarding the risk factors, symptoms and role of mammography. But some
      are still deficient in their knowledge regarding screening modalities and BSE
      method and time and role of chemotherapy. And this can be improved with further
      education.

PMID- 19579741
TI  - Renal cell carcinoma in presacral pelvic kidney.
AB  - Renal pelvic ectopia has been estimated to occur in 1 of 2100 to 3000 autopsies.
      Renal cell carcinoma (RCC) is a very rare phenomenon in an ectopic kidney.
      According to our review of literature, there are only seven reports of RCC
      occurrence in pelvic kidneys. We describe a patient with RCC of presacral ectopic
      kidney who underwent radical nephrectomy at our medical center.

PMID- 19579740
TI  - Gestational diabetes mellitus--a forerunner of chronic disorders in mother and
      child.
AB  - Gestational Diabetes Mellitus (GDM) can have serious immediate as well as long
      term consequences, both for the mother as well as the off-spring. It seems that
      women of south Asian origin are not only more likely to have GDM but also suffer
      more from the adverse consequences of the disorder. These consequences include
      the development of type 2 DM in women with a history of GDM and a higher risk of
      obesity and metabolic syndrome in the off-spring. Pakistani physicians should
      consider GDM seriously because the WHO states that rise in the prevalence of type
      2 DM will mainly occur in developing countries such as ours. Since GDM can lead
      to development of type 2 DM, efforts should be made to prevent type 2 DM through
      lifestyle modification strategies in this high risk population. It is important
      that we develop some clear cut guidelines for prevention and treatment of GDM.

PMID- 19579742
TI  - Mohr-Claussen syndrome or oro-facial-digital syndrome (OFDS) type-II.
AB  - The Mohr-Claussen syndrome or oro-facial-digital syndrome type II (OFD-II)] is
      characterised by tongue lobulation, midline cleft lip, high arched or cleft
      palate, broad nasal root with wide bifid nasal tip, hypertelorism, micrognathia,
      brachydactyly, syndactyly and polydactyly, bilateral reduplicated hallux,
      conductive hearing loss and normal intelligence. In view of the different modes
      of inheritance and the different prognoses of the two oro-facio-digital
      syndromes, type 1 and type 2, it is important to establish a correct diagnosis in
      these patients. A neonate with features of oro-facio-digital syndrome, type-II is
      being reported and the distinguishing clinicoradiological features with type-I
      are compared.

PMID- 19579743
TI  - Multiple major artery compression by an idiopathic aortic aneurysm: an unusual
      cause of hypertensive encephalopathy.
AB  - Multiple major artery compression by an aortic aneurysm is extremely rare in the
      paediatric population. Most arterial aneurysms in children are secondary to
      infections mainly mycotic, connective tissue disorder, vasculitis, collagen
      vascular diseases, and other causes. True idiopathic aneurysms are the least
      common and a few reports in children have been published. We describe an 8 year
      old boy who presented with hypertensive encephalopathy and later was found to
      have an idiopathic, symptomatic suprarenal aortic aneurysm compressing multiple
      major arteries of the abdomen. The child was subsequently managed on multiple
      antihypertensive medication and later required engraftment of the renal and
      inferior mesenteric artery. The diagnostic workup, surgical treatment, and a
      review of the literature is described.

PMID- 19579744
TI  - Atypical eclampsia.
AB  - Eclampsia occurring without prior signs and symptoms of preeclampsia is called
      atypical eclampsia. We present a case of 28 year old primigravida who developed
      intrapartum seizures. There was no prior clinical or biochemical evidence of
      preeclampsia. We have discussed the differentials of intrapartum seizures and a
      review of literature on atypical eclampsia.

PMID- 19579746
TI  - Stalking and mental health: do we need guidelines?

PMID- 19579745
TI  - Adrenal myelolipoma: a report of three cases and review of literature.
AB  - Adrenal myelolipoma is a rare and benign tumour composed of mature adipose tissue
      and haematopoietic elements that resemble bone marrow. It is mostly discovered
      incidentally on imaging of abdomen done for non adrenal related reasons or at
      autopsy. Usually asymptomatic, but has been reported to present with symptoms
      such as flank pain resulting from tumour bulk, necrosis or spontaneous
      retroperitoneal haemorrhage. Symptomatic tumours, growing tumours or tumours
      larger than 10 cm should be excised surgically. We report cases of 3 male
      patients presenting with flank pain and upper pole renal masses. All three were
      treated surgically with adrenalectomy. Myelolipoma was confirmed in all three on
      histology.

PMID- 19579748
TI  - Impact factor--a pandora's box.

PMID- 19579747
TI  - Awareness of stroke risk factors, signs and treatment in a Pakistani population.
AB  - OBJECTIVE: To assess the level of awareness in the general public on risk
      factors, symptomatology and immediate treatment of stroke. METHOD: A cross
      sectional study was conducted in a sample of subjects visiting a tertiary care
      university hospital by means of a self-designed questionnaire. The study period
      extended between May and June, 2007. RESULTS: A total of 398 individuals were
      surveyed. Hypertension (69.1%) and stress (55.8%) were identified as two major
      risk factors for stroke. Among them 50.8% identified "Brain" as the principal
      organ involved in stroke out of which 78.2% of the response came from people
      whose level of education was intermediate-and-above. Around 13% of the study
      respondents did not know of any risk factor for stroke, while 11.6% of the study
      respondents didn't know about the alarming signs of stroke. The most frequent
      response (26.16%) to immediate management of stroke was to take the individual to
      Emergency Department/hospital. In all 56% reported that basic information about
      stroke was given to them by friend/relative. CONCLUSIONS: The overall awareness
      of the study population regarding stroke was shown to be inadequate by this
      study. Knowledge was significantly greater in participants of younger age and a
      higher level of education.

PMID- 19579749
TI  - Second hand smoking: proper planning can reduce its health burden.

PMID- 19579750
TI  - "Quitting smoking is easy. I've done it a thousand times".

PMID- 19579751
TI  - Bilateral striopallidodentate calcinosis (Fahr's disease).

PMID- 19579752
TI  - The changing characteristics of neonatal sepsis in the neonatal intensive care
      unit: a never-ending challenge.

PMID- 19579753
TI  - Acute urticaria in children.
AB  - The fine article, "First Attack of Acute Urticaria in a Pediatric Emergency
      Department" by Liu et at, which appeared in the June issue of Pediatrics and
      Neonatology prompted me to submit comments and a review on the subject of
      urticaria in children, because this is indeed a pediatric problem that is
      frequently seen in clinical practice.

PMID- 19579754
TI  - Neonatal sepsis: a 6-year analysis in a neonatal care unit in Taiwan.
AB  - BACKGROUND: Neonatal sepsis is the most serious problem in neonatal intensive
      care, resulting in significant morbidity and mortality. We evaluated the
      causative pathogen, drug sensitivity, hematological parameters, clinical course
      and mortality rate of neonatal sepsis in a Taiwanese medical center and compared
      our results to those of previous studies conducted in Taiwan. METHODS: Neonates
      admitted to the neonatal intensive care unit (NICU) at National Taiwan University
      Hospital (NTUH) between January 2001 and December 2006 were included in this
      study. Patients were divided into early-onset sepsis and late-onset sepsis groups
      if their culture tested positive within the first 7 days of life or later,
      respectively. RESULTS: A total of 109 episodes of sepsis were identified in 100
      neonates. The incidence of sepsis was 4.06% among all NICU admissions. Most
      neonates with early-onset sepsis were term infants, while very low birth weight
      (VLBW) and preterm infants accounted for the majority of cases of late-onset
      sepsis. In early-onset sepsis, the most common pathogens responsible included
      group B streptococci (GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was
      associated with more meningitis involvement but lower incidence of mortality
      compared with E. coli. The most common causative microorganisms in late-onset
      sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The
      sepsis-related mortality rates were higher in early-onset sepsis (10%) than in
      late-onset sepsis (7%). CONCLUSION: Unlike previous reports from Taiwan, in the
      present study, GBS was found to be the leading pathogen in early-onset sepsis.
      GBS screening and intrapartum antibiotic prophylaxis guidelines should be used in
      Taiwan to prevent early neonatal sepsis. The most common causative microorganisms
      of late-onset sepsis were CONS and Candida species. Candida parapsilosis was
      associated with a high mortality rate.

PMID- 19579756
TI  - Natural course of neonatal progeroid syndrome.
AB  - BACKGROUND: Several progeroid disorders presenting a specific "old-man"
      appearance since birth or childhood have been described. Here, five patients with
      a history of severe intrauterine and postnatal growth retardation and
      pseudohydrocephaloid cranium noted after birth that were suggestive of neonatal
      progeroid syndrome (NPS) or Wiedemann-Rautenstrauch syndrome are reported. We
      discuss the natural course of the syndrome. METHODS: A series of anthropometric
      measurements, imaging, dual energy X-ray absorptiometry, and endocrine
      investigations to assess metabolic complications such as hyperinsulinemia and
      dyslipidemia were performed on these five patients who were followed for 1-7
      years. Screening of inborn errors, karyotyping, chromosomal breakage rates and
      DNA mutational studies with direct sequencing of LMNA, ERCC8 and ZMPSTE24 genes
      were also performed. RESULTS: Generalized lipodystrophy was noted in all patients
      except for regions such as the cheeks, hands and feet. All cases had failure to
      thrive, microcephaly, ear dysplasia, laryngomalacia, hearing impairment, gastro
      esophageal reflux disease, constipation, abnormal dentition,
      dermatitis/acrodermatitis enteropathica, hyperpigmentation of the skin, very low
      insulin-like growth factor I levels with delayed bone age, relative
      hypolipidemia, initial camptodactyly/joint contracture, progressive
      kyphoscoliosis, osteoporosis with loose joints, ventriculomegaly, and generalized
      organic aciduria. Other findings included inguinal hernia, hypothyroidism or
      persistent hyperthyrotropinemia, cryptorchidism, hip dysplasia, growth hormone
      deficiency, cloudy cornea with congenital glaucoma, neonatal teeth, cardiac
      defects, basal ganglia calcification and seizure disorder. These patients with
      NPS did not show hyperinsulinemia or dyslipidemia. Their karyotypes were all
      normal, while the chromosomal breakage test showed markedly increased breakage
      rates in four patients. LMNA, ERCC8, or ZMPSTE24 gene mutations could not account
      for the disorders in these patients. Four patients died after sepsis or
      aspiration pneumonia at the age of 1.1, 4, 6.2 and 7.5 years. CONCLUSION:
      Increased chromosomal breakage and the presence of basal ganglia calcification
      after early childhood suggest that DNA repair defects are involved in the
      pathogenesis of this disorder. This rare disorder represents a complex of
      symptoms with unknown cause and pathogenesis, and more than one disease may
      account for the clinical variability of NPS.

PMID- 19579755
TI  - Clinical manifestations, laboratory findings and complications of pediatric scrub
      typhus in eastern Taiwan.
AB  - BACKGROUND: Scrub typhus is a clinically important endemic disease in Taiwan. The
      aims of this study were to analyze the clinical manifestations, laboratory data
      and complications of pediatric scrub typhus in eastern Taiwan. PATIENTS AND
      METHODS: We searched medical records for all patients with scrub typhus who were
      hospitalized between 1992 and 2002 at the Taitung branch of Mackay Memorial
      Hospital, Taiwan. Records of children under the age of 18 with a confirmed
      diagnosis were selected for retrospective review. RESULTS: During the study
      period, 145 patients fulfilled the diagnostic criteria for scrub typhus, of whom
      106 (73%) were adults and 39 (27%) were children. The mean age of the children
      was 7.6+/-4.6 years. The most common clinical manifestations of pediatric scrub
      typhus were fever (n=39; 100%), cough (n=28; 72%), anorexia (72%), eschar (69%),
      chill (67%) and lymphadenopathy (64%). The most common complications were hepatic
      dysfunction (77%) and pneumonitis (54%). Three children (8%) required intensive
      care, but the overall survival rate was 97%. One child died with multi-organ
      failure within 8 hours after admission. CONCLUSION: Scrub typhus should be
      considered in children with fever and hepatic dysfunction, particularly in those
      with a history of environmental exposure in an endemic area for scrub typhus. The
      presence of an eschar offers an important diagnostic clue, but not for all cases.
      Children with scrub typhus may develop serious complications and may even die if
      appropriate treatment is not given. Doxycycline is an effective antibiotic for
      pediatric scrub typhus in Taiwan.

PMID- 19579757
TI  - Effect of blood transfusions on the outcome of very low body weight preterm
      infants under two different transfusion criteria.
AB  - BACKGROUND: Multiple packed red blood cell (PRBC) transfusions in very low birth
      weight (VLBW) prematurity have been suggested to be a risk factor for the
      development of retinopathy of prematurity (ROP) or for chronic lung disease
      (CLD). The purpose of this study was to examine the effect of PRBC transfusions
      on the outcome of VLBW prematurity. METHODS: In total, between July 2005 and June
      2006, 36 VLBW preterm babies were admitted to our neonatal intensive care unit
      and were randomly allocated to the "restrictive" (n= 19) or "liberal" (n= 17)
      criteria for PRBC transfusion. Complete blood count (CBC) was examined at
      admission and 30 days later. Reticulocyte counts, serum iron and ferritin were
      examined and compared with the clinical outcomes. RESULTS: Infants in the liberal
      group received a larger PRBC transfusion volume compared with the restrictive
      group over 30 days (41.7+/-20.1 vs. 27.2+/-15.9mL, p=0.029). There were no
      significant differences in the proportion of patients with respiratory distress
      syndrome, patent ductus arteriosus, severe intraventricular hemorrhage, ROP or
      CLD between the two groups. The laboratory data, except reticulocyte count,
      showed no significant difference on day 30. Further analysis of premature babies
      with and without CLD showed that total transfused blood volume greater than 30mL
      over 30 days was a risk factor for developing CLD in VLBW infants. CONCLUSION:
      Both criteria of PRBC transfusion had similar clinical outcomes, although liberal
      transfusion resulted in a greater amount of blood transfused and a low
      reticulocyte count at 30 days of age. We suggest restrictive criteria for
      minimizing the overall amount of transfusion to less than 30 mL may be a better
      way of preventing CLD in VLBW infants.

PMID- 19579758
TI  - Sonogram before and after pyloromyotomy: the pyloric ratio in infantile
      hypertrophic pyloric stenosis.
AB  - BACKGROUND: Sonography is used to diagnose infantile hypertrophic pyloric
      stenosis, but Little information is available about the appearance of
      postoperative sonographs. The purpose of this study was to evaluate the
      morphology of the pylorus in association with an obstruction before and after
      pyloromyotomy. METHODS: Pyloric length, diameter, muscle thickness and
      intermuscular space were measured sonographically at diagnosis and daily after
      pyloromyotomy until discharge in 12 infants with infantile hypertrophic pyloric
      stenosis. The ratios of pyloric wall thickness and intermuscular space to the
      entire pyloric diameter were measured. RESULTS: The pylorus still appeared
      hypertrophied after pyloromyotomy on the sonograms. The traditional measurement
      of linear dimensions of the pylorus was not significantly changed from the
      preoperative values by the time of discharge, except for muscle thickness. The
      intermuscular space increased from 4.8+/-0.8 mm preoperatively to 7.3+/-2.1 mm by
      postoperative day 3 (p=0.10). Lowe's pyloric ratio at diagnosis was a mean of
      0.32, decreasing to 0.29 on postoperative day 3 and 0.29 on the day of discharge
      (p=0.82). The alternative pyloric ratio increased significantly by postoperative
      day 2 (0.24+/-0.09 on day 2 vs. 0.11+/-0.07 preoperatively, p=0.02). CONCLUSION:
      The pyloric ratio appears to be a reliable parameter in evaluating the regression
      of pyloric stenosis after pyloromyotomy, and also aids in the diagnosis of
      pyloric stenosis.

PMID- 19579759
TI  - Spontaneous perirenal urinoma associated with ureteropelvic junction obstruction
      in a child: a case report.
AB  - We report a case of a 10-year-old Taiwanese boy with a perinephric urinoma, whose
      health had previously been good, but who experienced a sudden onset of severe
      Left flank pain. Radiological examination revealed ureteropelvic junction
      obstruction with grade IV hydronephrosis and perinephric urinoma of the left
      kidney. ercutaneous drainagewas performed successfully to relieve these symptoms.
      ication of congenital obstruction of the urinary tract, and it following renal
      trauma.

PMID- 19579760
TI  - Glycogen storage disease type Ib: the first case in Taiwan.
AB  - Glycogen storage disease (GSD) type Ib is caused by the deficiency of glucose-6
      phosphate translocase activity. The elder brother of the proband died at age 20
      months, and GSD Ia, a disease caused by the deficiency of glucose-6-phosphatase,
      was the diagnosis. Theproband developed hypoglycemia shortly after birth. Dietary
      therapy was instituted immediately, but his growth was poor and there were
      repeated episodes of pyogenic infection. Neutropenia had been observed since 6
      months of age, but the diagnosis of GSD Ib was established only at 18 months of
      age two mutations (c.354_355insC (p. W118fsX12) and c.736T>C (p.W246R)) were
      detected on his SLC37A4 gene. Regular administration of G-CSF rapidly improved
      his health and decreased his hospital stay. Although GSD Ib is very rare in
      Taiwan, correct diagnosis is essential to save the lives of such patients.

PMID- 19579761
TI  - Management of sigmoid volvulus based on Ladd's procedure: a case report.
AB  - Sigmoid volvulus is a rare but potentially life-threatening condition in
      childhood. Colectomy is usually required to prevent recurrent volvulus, which
      carries a high risk of morbidity and mortality. Here, we report a non-resection
      method based on the concept of Ladd's procedure to treat a sigmoid volvulus in a
      15-year-old boy. After reduction of the volvulus, the distance between the
      sigmoid-rectal junction and the sigmoid-descending colon junction was widened by
      dissecting the meso-sigmoid colon along the course of the long axis. No colon
      resection was performed. The total operation time was less than an hour. The post
      operative recovery was uneventful. There was no recurrent volvulus during a
      follow-up of 1 year. Widening the base of the mesosigmoid according to the
      concept of Ladd's procedure may be considered as a more simple and safe
      alternative treatment to prevent recurrent sigmoid volvulus in children.

PMID- 19579762
TI  - [Tributyltin compounds--the substances noxious to health].
AB  - Tributylotin (TBT) compounds are lipophilic substances having low vapour pressure
      TBT have been used as an active ingredient in molluscicides, antifoulants and
      wood preservatives, disinfectants and as biocides used in cooling systems, pulp
      and paper mills, leather processing, and textile mills. TBT acute poisoning in
      humans were manifested by hepatic functional changes, hypoglycemia, glycosuria,
      and respiratory system disturbances, similar to asthma. In experimental animals
      these compounds exerted mainly immunosuppressive, endocrinopathic, neurotoxic,
      hepatotoxic, nephrotoxic, and skin and eye irritative effects. Mutagenic,
      genotoxic and carcinogenic activity of TBT have not been confirmed. However
      gonadotoxic, embryotoxic, fetotoxic, and developmental effects were observed. In
      this article the actual views on the mechanisms of TBT toxic effects have been
      described. In conclusion, TBT may be a potential hazardous to human health.

PMID- 19579763
TI  - Atomic forms of selenium in selected mineral and well waters in Poland.
AB  - The study aimed at application of a high performance liquid chromatography (HPLC)
      with UV detector for selenium speciation in samples of mineral and well waters in
      Poland. Basic solutions 1000 microg/l SeO3(2-) and SeO4(2-) were prepared by
      dissolving 2.190 g of reagent Na2SeO3 and 2.393 g Na2SeO4 in 1000 ml of deionised
      water, respectively. Recent standards SeO3(2-) and SeO4(2-) (single or mixed)
      were prepared daily. Chromatographic separations were obtained on a column with
      reversed phase of C18, 250*4 mm, 5 microm ODS. As mobile phase mixture of 5
      mmol/l phosphate tetrabutylammonium, 50/50 water/methanol at pH 3.4 was used.
      Flow rate of mobile phase was 1 ml/min and detector was set on lambda = 210 nm.
      Injection volumes were 5 microl. The average concentration of Se(IV) was 4.10
      microg/l and Se(VI) - 4.27 microg/l and Se(II) - 0.54 microg/l although the
      differences between water samples originating from various sources were
      relatively high. The developed method can be therefore recommended for
      determination of Se in samples of mineral water.

PMID- 19579764
TI  - [Determination of azaperone and carazolol residues in animals kidney using LC
      MS/MS method].
AB  - The method is presented to analyze azaperone and carazolol in pigs kidney.
      Samples were extracted with acetonitryle. The determination was performed by LC
      ESI-MS/MS. The LC was equipped with column Luna C18 Phenomenex. Haloperidol was
      used as internal standards. The method was validation according to the criteria
      of Decision Commission No 2002/657/EC. Recoveries for the level 100 microg/kg
      azaperone and 25 microg/kg carazolol were in the range 91.2-107.0% and 70.8
      93.2%. The limit of decision (CCalpha) and detection capability (CCbeta) was
      respectively 125.9 microg/kg, 160.0 microg/kg for azaperone and 29.3 microg/kg,
      33.3 microg/kg. LC-MS/MS technique fulfill the requirements of Decision
      Commission No 2002/657/EC.

PMID- 19579765
TI  - [Comparative assessment of carotenoids intake by food frequency questionnaire and
      4-day dietary food records method].
AB  - The aim of the work was comparative assessment of beta-carotene, lycopene and
      lutein intake by two methods: food frequency questionnaire and 4-day dietary food
      records. Subjects were 130 female volunteers, aged 18 to 25 years, Warsaw
      University of Life Sciences students. Data were collected in spring/summer 2005.
      Intakes of beta-carotene (3.62 vs. 3.49 mg/day per person), lycopene (4.54 vs.
      4.05 mg/day per person) and lutein (2.50 vs. 2.12 mg/day per person,
      respectively) estimated these methods were not statistically significant. The
      mean differences in intakes assessed were higher for food frequency questionnaire
      (respectively 3.7% for beta-carotene; 12.1% for lycopene; 1.9% for lutein).
      Statistically significant Pearson correlations were observed between estimation
      of carotenoids intake by two methods (r = 0.82 for beta-carotene, r = 0.75 for
      lycopene, r = 0.73 for lutein; p < 0.001). Main sources of beta-carotene were
      vegetables supplied 90% of this carotenoid (therein carrot 54%). Tomato products
      and fresh tomatoes contributed 60-61% and 30% of lycopene/day respectively.
      Sources of lutein were fresh vegetables contributed to diet 54-60% of lutein
      (therein leafy vegetables 25-30%).

PMID- 19579766
TI  - [Evaluation of lycopene intake in daily food rations of women from the Lower
      Silesia region].
AB  - The aim of this study was to assess lycopene intake in daily food rations of
      women (n = 725) from the Lower Silesia region. The data on the lycopene intake
      were collected using 24-hour recall and diet history questionnaire. The intake of
      lycopene was not too low. The average lycopene contents in the daily food rations
      of 725 women from Lower Silesia region was 7.5 mg. The highest lycopene intake
      was found in the food daily rations of women with BMI > 30. In examined group of
      women low knowledge on the importance of the role of lycopene in health was
      noticed. Educational interventions are required to inform women and to increase
      lycopene intake among them.

PMID- 19579767
TI  - [Consumption of fruits and vegetables among university and college students in
      Gdansk and Sopot].
AB  - The aim of the study was the determination of daily servings consumption and
      evaluation of frequency consumption of fruit and vegetables among university and
      college students. The study was carried out on the group of 180 students and was
      assessed by means of food frequency questionnaire. Students mostly ate from 1 to
      2 servings of vegetables and 2 servings of fruit per day. The most commonly
      consumed vegetables were: tomatoes, carrots and onions. The most commonly
      consumed fruits were: apples, bananas, lemons and tangerines. Consumption of both
      vegetables and fruits was to low to cover daily recommendations.

PMID- 19579768
TI  - [Dietary errors of junior high school girls and the risk of disorders of dietary
      origin].
AB  - The aim of the study was to investigate the dietary habits and hazards ensuing
      from poor nutrition among junior high schoolgirls. The research encompassed 100
      randomly chosen girls at the age of 15, in the third class of junior high school.
      The research tool was an anonymous questionnaire. Girls with proper body weight
      constituted 74%, whereas 26% were underweight. The surveyed girls made many
      dietary errors, such as long breaks between meals, not having the supper eating
      the last meal too late. 39% did not accept their appearance and 44% applied
      slimming diet earlier. The vast majority of the pupils (88%) gave their attention
      to the media promoting a very thin figure. In certain conditions, such behaviour
      can lead to disorders of dietary origin.

PMID- 19579769
TI  - [Nutrictional behaviours of men at the age 20-60 with regard to anthropometric
      indicators of nutritional status].
AB  - The aim of this research was to analyse eating behaviours of men in regard to
      selected anthropometric indicators of nutritional status (BMI and waist
      circumference). The test sample for this research were men aged 20-40 (n = 592)
      and 40-60 (n = 802) employees of Tadeusz Sendzimir Steel Mill in Cracow. The
      indices of nutritional status were established on the basis of anthropometric
      measurements, whereas eating behaviours were described on the basis of an
      authorial questionnaire. Statistical analysis of data was conducted by means of
      chi2 independence test. The research corroborated the existence of a correlation
      between BMI and waist circumference indices and certain male eating behaviours.
      Having 1-2 meals per day was to be observed among men with a higher BMI, whereas
      having 4-5 meals per day among men with a healthy BMI (p < 0.01). Younger men
      with proper body weight declare a higher regularity of having meals than obese
      ones (p < 0.05). This research has not found any correlation between BMI and
      waist circumference indices and the frequency of eating vegetables, fruit, fish
      and "fast-food" products. However a tendency among obese men to cut down on
      eating sweets has been discovered (according to BMI), irrespective of their age,
      as compared to men with proper body mass (p < 0.05). The same phenomenon was also
      confirmed in the group of younger men in the waist circumference category (p <
      0.05). Hence, correlations exist between psychosomatic indices and certain eating
      behaviours of men aged 20-60, which explain the development of obesity. At the
      same time obese men tend to rationalise certain eating behaviours, whose purpose
      is to reduce excessive body weight.

PMID- 19579770
TI  - [Assessment of selected features of the lifestyle being conduicive to the state
      of health of 16-18 year old girls. Part I. Dieting, physical activity, smoking
      and drinking alcohol].
AB  - The aim of the study was to analyze health attitude of 409 16-18 year old girls
      from Wroclaw in three areas: physical activity, dieting, and smoking and alcohol
      use. Research indicated different levels of underweight among 17.4% of girls,
      overweight and obesity among 11.2% of girls, and inappropriate level of physical
      activity among 60% of girls. Negative self-evaluation of own appearance among 50%
      of girls contributed to dieting among 32% of girls. Studies indicated as well
      that 49% of girls smoke, and 89% of girls drink alcohol occasionally or every
      week.

PMID- 19579771
TI  - [Nutrition mode evaluation among University of Agriculture students in Szczecin
      in 2006. Part I. Consumption of selected nutrients and nourishment state].
AB  - The aim of the study was the evaluation of nutrients contents in daily food
      rations and state of nourishment of 126 students (111 women, 15 men) from
      Szczecin University of Agriculture. The supply of 24 nutrients was determined by
      24-hours nutritional interview method. It was shown, that student's diets were
      characterised by inappropriate proportion of majority analyzed nutrients (women-
      17, men --10). The lowest intake concerned vitamin D, copper calcium and fiber
      (22 - 63.4% of RDA) and the biggest: sodium, phosphorus, vitamin A and B12 (143.6
      481%). Body mass index has shown that the body weight of 66.6 - 69.8% of the
      examined students was in accordance with the norms.

PMID- 19579772
TI  - [Evaluation of nutrition and physical activity of students in Gastronomic School
      in Bialystok].
AB  - The aim of this study was to estimate nutrition and physical activity of students
      in Gastronomic School in Bialystok. Questionnaire about nutrition and physical
      activity took on April 2008 in 74 students. The content of energy and main
      nutrition values were calculated and compared to the recommended values. Students
      diet included normal of energy, protein, fats and carbohydrates. Only 58% girls
      and 61% boys had intensive physical activity. Change of nutrition and moderate in
      physical activity is recommended for the students.

PMID- 19579773
TI  - [Evaluation of the energy balance of health resort visitors during 21 days
      staying in the sanatorium].
AB  - The aim of the work was to count the energy balance in health resort visitors and
      its influence on body mass change in those patients. On the basis of observations
      and analysis of the obtained results it is claimed that the diets used by
      patients were improperly matched to their sex. Women were using diets with too
      high caloric value, which resulted in rise of BMI (Body Mass Index) and body
      mass. On the other hand, in the group of males the energy balance was negative.
      These caused the reduction of BMI and body mass, but not to the correct level.
      The stay in sanatorium should be the lesson for the patient how to use the proper
      diet. The correct diet which is dependant on the age, sex, height and the work
      load should be set more carefully by the medical staff.

PMID- 19579774
TI  - Body mass index (BMI) and dietary preferences of women living in rural areas.
AB  - The aim of the study was to examine the relationship between the BMI of women
      living in rural areas and their dietary habits, taking into consideration the
      regularity and frequency of consumption as well as preferences in various groups
      of foodstuffs. The study included 60 women aged 23 - 69, living in one county.
      The women were divided into two groups according to nutritional status (BMI):
      group I with normal body weight and group II with overweight and obesity. Dietary
      habits were evaluated by using the anonymous and voluntary questionnaire. The
      questionnaire contained questions concerning dietary preferences. The results
      were statistically analyzed. The study indicated that a vast majority of
      overweight and obese women in rural areas prefer fried dishes, red meat and
      animal fats. However they do not consume vegetables and fruit frequently enough.
      Such dietary habits will only increase problems with obesity in rural
      communities. Thus it is important to start nutrition education as a significant
      strategy for non-pharmacological treatment of obesity and its health effects.

PMID- 19579775
TI  - [Evaluation of the knowledge of atherosclerosis prevention among the inhabitants
      of the Lublin region].
AB  - The major aim of the work was to assess the awareness of risk factors and
      atherosclerosis prevention among the inhabitants of the Lublin region. The
      anonymous and voluntary questionnaire survey was carried out in winter 2007
      (January - February) among 152 inhabitants of Lublin and surroundings. The
      anonymous questionnaire method was applied to assess the usual way of nutrition
      and the knowledge of atherosclerosis prevention rules. The questionnaire
      concerned among others: nutrition regularity, consumption frequency, preference
      levels of different kinds of food products, the knowledge of atherosclerosis
      prevention rules and the health condition of the respondents as well. The
      anthropometric data was also analysed and the BMI was measured. This survey shows
      that despite the declared knowledge of cardiovascular disease prevention rules
      the majority of the respondents did not apply them, which can be exemplified by
      the BMI percentage and screening frequency. Also the way of nutrition of the
      analysed population is inadequate due to numerous inconsistences with current
      nutritional rules.

PMID- 19579776
TI  - [Plasma homocysteine level and selected dietary habits in young healthy men].
AB  - Elevated plasma homocysteine level is recognized as independent risk factor for
      cardiovascular disease (CVD). Homocysteine metabolism in the body is precisely
      regulated by many factors including dietary habits as folic acid, vitamin B6 and
      B12 daily intakes. Data concerning the relationship between methionine daily
      intake and plasma homocysteine concentrations are contradictory indicating
      increased or decreased plasma homocysteine levels in response to high protein or
      high methionine daily intakes. This study aimed at the evaluation of the
      relationship between habitual dietary habits of young, healthy men and plasma
      homocysteine levels. A total of 65 healthy students volunteered to participate in
      the study. Their dietary habits were assessed from 4 dietary records concerning
      daily food intake during two week days and weekend. Macronutrient, methionine and
      vitamin B6 intakes were calculated using FOOD 2 computer program purchased from
      Institute of Food and Nutrition in Warsaw. Blood was drawn from antecubital vein
      after overnight fast. Plasma homocysteine concentration was determined by
      fluorescence polarization immunoassay using commercial kits from Abbott (USA). It
      has been demonstrated that plasma homocysteine levels were significantly and
      inversely correlated with daily total protein intake (r = -0.372, p = 0.003) and
      to lesser extent with methionine nutritional density (r = -0.319, p = 0.02).
      There were no correlation between daily vitamin B6 intake and plasma homocysteine
      concentration. Assuming our results it could be postulated that habitual daily
      intake of protein and consequently methionine has a beneficial effect on plasma
      homocysteine levels in young healthy men. In addition, it seems feasible that
      protein effect on plasma homocysteine is due to methionine and protein-originated
      vitamins action.

PMID- 19579778
TI  - [Antagonistic interactions between saprotrophic fungi and geohelminths. 1.
      Saprotrophic fungi in the biological control of phytopathogenic geohelminths].
AB  - The state of knowledge on the possible antagonism between soil saprotrophic fungi
      and phytopathogenic nematodes of the genera Meloidogyne, Heterodera, and
      Globodera is reviewed basing on the literature and our own research. Mycelial
      colonisation of various developmental stages of these geohelminths is the most
      common factor thought to reduce their populations in nature. The following
      parasitic fungi can be found on the cysts, eggs, as well as the larvae of the
      nematodes: Paecilomyces lilacinus, Verticillium chlamydosporium, Cylindrocarpon
      destructans, Pochonia chlamydosporia, Fusarium spp., and Penicillium spp. The
      fungi invade the nematodes, such as Heterodera, Globodera, or Meloidogyne,
      "passively" penetrating through the natural orifices of the cysts, eggs, and
      larvae of the host. Equally frequent, however, is a biochemical action of the
      fungi prior to colonisation, which is linked with production of mycotoxirls or
      hydrolytic enzymes. Such an active way of fungal penetration of various stages of
      the phytopathogenic nematodes has been observed in Pochonia chlamydosporia,
      Penicillium verrucosum var. cyclopium, P. frequentans, Sclerotinia rolfsii,
      Rhizoctonia solani, and Fusarium spp. Triacylglycerols (TAG), phenols, as well as
      trichothecene, T-2, have been found in the metabolites extracted from mycelia of
      these species. Predation by fungi is also a factor that may reduce a population
      of phytopathogenic nematodes. This form of antagonism is characteristic for
      nematicidal fungi of the genera Arthrobotrys and Dactylella. These fungi form
      shrinking rings and hooks in their mycelia by which the fungus entangles and
      paralyses a migrating form of nematode. Despite the fact that the antagonism
      between fungi and nematodes is a commonly occurring phenomenon observed in the
      soil, the nematicidal and nematotoxic properties of fungi have not a wide
      application in biological plant protection. Up till now, only the bionematicides
      based on Arthrobotrys robusta (Royal 300 and Royal 350) as well as Paecilomyces
      lilacinus (Biocon and PL Plus) have found its commercial application.

PMID- 19579777
TI  - [Evaluation of influence of diet content and its supplementation with chosen
      group of B vitamins on lipids and lipoprtoteins concentration in female rat
      serum].
AB  - The influence of diet content and its supplementation with chosen group of B
      vitamins on the intake of feeding stuff increase, changes of body mass,
      accumulation of fat tissue, lipids and lipoproteins concentration in the blood of
      female rats were under research. The animals, aged 5 months, were divided into
      three groups (8 persons each) and fed ad libitum with granulated Labofeed B type
      mix. Group I with the basic mix containing among other things whole grain, Group
      II with a modified mix, where whole grain was replaced by wheat flour and
      saccharose and Group III with modified mix supplemented in excess with chosen
      vitamins of B group. This experiment took 6 weeks during which the amount of
      consumed feed was currently evaluated, and the body mass was controlled weekly.
      After finishing the experiment in the obtained serum the concentration of
      triacylglycerols, complete cholesterol with enzyme method and the content of
      cholesterol fractions with electrophoretic separation method were determined.
      Analysis of fat content in muscles and livers was conducted and the amount of
      round the bodily organ fat was determined. It was ascertained that change of the
      content of the feed and its supplementation with the chosen B group vitamins did
      not influence in a substantial way its intake and the increase of body mass,
      however it had influenced substantially, in animals fed with the modified feed
      the accumulation of round the organ fat and in supplemented the intramuscular
      fat. Analysis of the results enabled the ascertainment that the diet
      supplementation with chosen ingredients of the B group vitamins corrects the
      negative effect of accumulation of the visceral fat tissue as a result of the
      change of its contents, caused substantial increase in the concentration of
      triacylglycerols, complete cholesterol and its fractions VLDL- and LDL- with
      simultaneous decrease of the concentration of cholesterol HDL- fractions.

PMID- 19579779
TI  - [Antagonistic interactions between saprotrophic fungi and geohelminths. 2.
      Saprotrophic fungi in biocontrol of parasitic geohelminths of humans and
      animals].
AB  - The soils ecosystem plays an important role in the epidemiology of geohelminth
      diseases of humans and animals. Soil contamination with ova of the parasitic
      geohelminths represents a global public health-hazard issue. Biological agents
      have been thought to control the infective forms of parasites present in the
      soil. Biocontrol of geohelminths represents an alternative to pesticides (i.e.,
      nematicides), which are not efficient in killing infective nematode forms and,
      additionally, result in the environment pollution and long-term disturbances in
      the soil ecosystem homeostasis. The degree of the inhibiting effect of soil
      saprotrophic fungi on geohelminth embryonic development varies and depends on the
      species. A number of fungi cause various morphological disorders in the embryos
      of developing parasitic nematodes, but also have an ovicidal effect. Although the
      nature of the antagonism between fungi and other living organisms has not been
      fully explained, it is certain that mycotoxins and fungal enzymes constitute its
      important components. Considering the studies carried out so far, the
      antagonistic effect of mold fungi against the infective stages of geohelminths
      can be fully recommended as a real control factor, especially as these
      saprotrophs represent a natural factor within the soil environment, that is of
      particular biochemical activity.

PMID- 19579780
TI  - [Biofilm caused by fungi--structure, quorum sensing, morphogenetic changes,
      resistance to drugs].
AB  - Formation of fungal biofilms in patients with implanted biomedical prosthesis
      constitutes very serious clinical problems. The biofilm can lead to dysfunction
      of implanted material and can be a reservoir for chronic and systemic infections.
      Numerous investigations demonstrated differences in quantity and structure of
      biofilms that had been formed by various species of fungi belonged to Candida
      genus. Stages of biofilm formations had been examined carefully in in vitro
      conditions. Biofilm formation begin with adhesion of fungi to the surface,
      microcolonies are formed subsequently. At the end of the process, extracellular
      material is excreted, and its formula, that is various in different fungi Candida
      species, contribute to its resistance to antifungal drugs. Farnesol and tyrosol
      are two quorum-sensing molecules. They are acting inversely, regulating formation
      of "germ tubes" and influencing morphogenetic conversion between yeast and
      filamentous forms, which plays a very important role in pathogenicity and
      formation of biofilm. Drug resistance of fungi from Candida has been shown to
      create a very important clinical problem. Many experiments in vitro confirm
      significantly lower activity of antifungal drugs toward Candida biofilm than
      toward Candida, in the form of planctonic cells. Surprisingly, some non-steroidal
      anti-inflammatory drugs can inhibit biofilm formation.

PMID- 19579781
TI  - [Occurrence of coccidia from genus Eimeria in European bison in Bialowieza
      Forest, Poland].
AB  - Protozoa from the genus Eimeria belong to the least recognized parasites of the
      European bison. There are only a few data concerning the infection of the bison
      by these protozoa in Bialowieza Forest. In the winter of 2007/2008 weighting 3 g
      fecal samples from the rectum of 16 shot bison were examined by flotation method.
      In 13 of them were found coccidian oocysts from genus Eimeria, which were
      determined to the species by morphometric study under the microscope. In all 13
      positive samples, it is 81.2%, oocysts of Eimeria bovis were found. Intensiveness
      of this infection oscillated from 1 to 181 and the mean one was 38 oocysts. E.
      zuernii was found in 9 samples in the mean intensity 19 (1-154) oocysts. E.
      ellipsoidalis occurred in 3 bison with a very low intensity 1 to 3 oocysts. The
      most rarely occurred E. canadiensis, only in 2 examined bison in the number of 2
      and 3 oocysts. All found coccidian species are the typical parasites of cattle.
      Bialowieza Forest is a new place of occurrence of these parasites. European bison
      is a new host for E. zuernii.

PMID- 19579782
TI  - [Sarcocystis cruzi (Protozoa: Apicomplexa: Sarcocystiidae) infection in european
      bison (Bison bonasus) from Bialowieza Forest, Poland].
AB  - Samples of oesophagus, diaphragm and heart muscles were taken from one European
      bison from Bialowieza Forest during seasonal European bison elimination in 2008.
      Five gram of each muscle was examined by staining small samples in 0.2% aqueous
      solution of methylene blue. After that they were placed between compressor
      glasses and examined under a dissecting microscope in order to detect Sarcocystis
      sp. infection. All sarcocysts observed were counted. The 5-g sample of the heart
      muscle yielded a total of 756 sarcocysts while that of the diaphragm contained
      107 of them and that of the oesophagus--89. All of the sarcocysts were isolated
      from 1 g of each muscle by using preparation needles (probes). After that the
      sarcocysts were taken to 0.5% physiological solution and examined under light
      microscope. The special attention was paid to detection of their cyst wall, which
      was thin (1 microm up to 1.2 microm) and smooth in all cases. Sometimes villar
      protrusions were seen on the surface of the cysts. Differences between the size
      of sarcocysts isolated from different muscle samples were observed. The longest
      and the slenderest sarcocysts were found in the diaphragm. Slightly smaller in
      the oesophagus and the smallest ones in the heart muscle tissue. The average size
      of sarcocysts isolated from diaphragm was 957.6 microm x 112.7 microm. Sarcocysts
      found in the oesophagus measured 484.1 microm x 194.6 microm and those isolated
      from the heart muscle attained 305.4 microm x 103.9 microm. All of the sarcocysts
      isolated from heart, oesophagus and diaphragm muscles were identified Sarcocystis
      cruzi.

PMID- 19579783
TI  - [Occurrence of Eimeria protozoa in lambs in Western Pomerania, Poland].
AB  - A total of 250 Merino lambs from the Lubuskie province and 83 Suffolk lambs from
      the Zachodniopomorskie province were examined. The level of infection with
      Eimeria protozoa was determined on coproscopic examinations using the Willis
      Schlaaf flotation method. The species composition of the coccidia was determined
      using Pellerdi's system. The prevalence of lamb infection with coccidia averaged
      85.18% in the Zachodniopomorskie province and 55.32% in the Lubuskie province.
      Coproscopic examinations showed that the animals were infected with different
      species. Eight species were isolated from faecal samples: E. faurei, E.
      ovinoidalis, E. pallida, E. intricata, E. parva, E. arloingi, E.
      ninakohlyakimovae and E. granulosa. E. parva (53%) and E. ninakohlyakimovae
      (47.8%) were the dominant in the Zachodniopomorskie province, and E.
      ninakohlyakimovae (65%) and E. intricata (43.3%) in the Lubuskie province.

PMID- 19579784
TI  - Ticks (Acari: Ixodida) parasitizing bats in Poland and Slovakia.
AB  - We summarize the previously published reports and the results of our own research
      about distribution of ticks parasitizing bats in Poland and Slovakia. Five
      species of ticks infesting bats were recorded: Carios vespertilionis, Ixodes (E.)
      vespertilionis, I. (P.) simplex, I. (I.) ricinus and I. (Ex.) trianguliceps. Two
      last species were observed only on bats in Poland. C. vespertilionis, I.
      vespertilionis and I. simplex are specific parasites of bats. C. vespertilionis
      was recorded on 37 sites in Poland and 7 in Slovakia. Fourteen species of bats in
      Poland and 5 in Slovakia were parasitized by this species. I. vespertilionis was
      collected from 6 bat species both in Poland and Slovakia respectively on 22 and
      11 sites, respectively. The remaining species have been reported very rarely.

PMID- 19579785
TI  - [Use of the presence of cellulose in cellular wall of Acanthamoeba cysts for
      diagnostic purposes].
AB  - Species identification within the genus Acanthamoeba is based predominantly on
      morphological and biochemical features. It is labor-intensive and requires
      cloning and axenization. We described a novel immunocytochemical method for the
      identification of Acanthamoeba spp. based on selective binding of Clostridium
      cellulovorans cellulase to protozoan cyst wall cellulose. Free-living amoebae
      isolated from different water sources by filtration and subsequent cultivation on
      non-nutrient agar were assigned to genera Acanthamoeba, Naegleria or Hartmannella
      using morphological taxonomic criteria. Tissues samples from experimentally
      infected mice were fixed in formalin and for sectioning embedded in paraffin or
      snap frozen. The Cellulose-Binding Domain of C. cellulovorans cellulase (CBD)
      obtained as a recombinant protein, were coupled to the fluorescent dye using
      Alexa Fluor350, 488, 568 - Protein Labelling Kit or labelled with the biotin
      using EZ-Link Sulfo-NHS-Biotin. All coupling procedures were performed according
      to the methods provided by manufacturers. For staining with CBD conjugate, slides
      containing cysts collected from the agar plates or tissue sections were immersed
      with PBS and incubated with CBD for 30 min at room temperature, washed 3 times
      with PBS. For staining with CBD-biotin slides containing cysts were incubated
      with biotinylated CBD for 30 min at room temperature. Subsequent washings in
      changes of PBS were followed by the incubation with Strept ABComplex/HRP, for 30
      min at room temperature, than 3,3 diaminobenzidine tetrahydrochloride was added
      for 15 min. Slides were rinsed with water, dried and examined in the light
      microscope. We showed that cellulose could be easily detected by
      immunofluorescence using conjugated CBD in the inner cyst wall of Acanthamoeba
      spp. The reference strains of Acanthamoeba spp. and all Acanthamoeba strains
      isolated from water and from tissues of infected animals gave positive reaction.
      CBD prepared as a biotynylated protein can be also used for the demonstration of
      Acanthamoeba cyst in infected tissues and environmental samples.

PMID- 19579786
TI  - Description of Paratrichodina yangtzeus sp. n. (Ciliophora: Trichodinidae) from
      the freshwater fishes in the Yangtze River, China.
AB  - Paratrichodina Lom, 1963 comprises more than ten species. Paratrichodina has been
      found so far in various freshwater, marine fishes and amphibians worldwide. This
      report provides the first record of Paratrichodina from freshwater fishes in
      China. Smears with trichodinids were air-dried and then the slides with
      trichodinid ciliates were impregnated with Klein dry silver impregnation
      technique in order to reveal details of the adhesive disc. All measurements are
      presented in micrometres and follow the system proposed by Lom. Detailed
      descriptions of the denticles are presented in accordance with the method
      proposed by Van As and Basson. Denticulate ring of the studied specimens is
      constituted by loosely arranged denticles and the adoral ciliary spiral is
      between 180 to 200 degrees. So the studied specimens were assigned to
      Paratrichodina. The presently described trichodinid resembles P. erectispina Lom
      et Haldar, 1977 and P. voikarensis Kashkovsky et Lom, 1979, but it is clearly
      distinguished from P. erectispina by the shape of denticle and some other
      measurements. Based on its unique characteristics, a new Paratrichodina species
      is erected, and named Paratrichodina yangtzeus sp. n.

PMID- 19579787
TI  - Arthropods (Acari, Mallophaga, Siphonaptera) collected from Procyon lotor
      (Linnaeus, 1758) (Mammalia, Carnivora, Procyonidae) in Poland.
AB  - From 9 specimens of Procyon lotor collected in vicinity of Dobroszyn and Gorzyca
      (Lubuskie province) 61 arthropods of 6 species were obtained: Siphonaptera (one
      specimen), Acari (3 species), Phthiraptera (one specimen--Trichodectes
      octomaculatus; new species to fauna of Poland) and one specimen of Psocoptera.

PMID- 19579788
TI  - Ophionyssus saurarum (Acari, Mesostigmata) infecting Lacerta agilis (Reptilia,
      Lacertidae).
AB  - Thirty specimens of sand lizard, Lacerta agilis, were analyzed and Ophionyssus
      saurarum was found on three of them. These parasitic mites were located in the
      ear opening of the host. The only lizard specimens which were infested were those
      that inhabit areas degraded by human activity.

PMID- 19579789
TI  - [Animal reservoirs of human virulent microsporidian species].
AB  - The main objective of the present study was to determined the occurrence of
      Encephalitozoon intestinalis, E. hellem, E. cuniculi, and Enterocytozoon bieneusi
      in Poland in animal faecal using the FISH (Fluorescent In Situ Hybridization) and
      multiplex FISH techniques. Additional objectives included: (1) identification of
      animal hosts of microsporidia that are infectious to humans amongst free-ranging,
      captive, livestock and domestic animals; (2) a molecular analysis of randomly
      selected parasite isolates and determination of their zoonotic potential; (3)
      evaluation of the role of animals in the dissemination of microsporidia spores in
      the environment, and an estimation of the potential risk of infection for other
      animals and humans. A total of 1340 faecal samples collected from 178 species of
      animals were examined using conventional staining (chromotrope-2R and calcofluor
      white M2R staining) and molecular techniques (FISH and multiplex FISH
      techniques). Microsporidian spores were detected in 33 faecal samples (2.5%)
      obtained from 17 animal species. Microsporidia were demonstrated more often in
      birds (6.1%) than in mammals (0.7%); the difference was statistically significant
      (p < 0.00001). In addition, the prevalence of microsporidian infections in
      waterfowl was significantly higher than the prevalence of microsporidian
      infections in other animals (p < 0.03). Animal reservoirs of human infectious
      microsporidia were disclosed in six of 38 sites where faecal samples were taken
      from animals. Three species of human virulent microsporidia were identified in
      animals. Spores of E. hellem were found in 25 faecal samples (1.9%) taken from 12
      bird species (6 zoo bird species, 4 free-ranging bird species, 2 livestock bird
      species). Spores of E. intestinalis were identified in five faecal samples (0.4%)
      taken from two livestock bird species and two zoo mammal species. In turn, E.
      bieneusi spores were detected only in three faecal samples (0.2%) taken from
      three zoo mammal species. It was demonstrated that the new hosts of E. hellem are
      the following bird species: mallard duck (Anas platyrhynchos), greyleg goose
      (Anser anser), mute swan (Cygnus olor), black-necked swan (Cygnus melancoryphus),
      black swan (Cygnus atratus), coscoroba swan (Coscoroba coscoroba), black-crowned
      crane (Balearica pavonina), nicobar pigeon (Caloenas nicobarica) and carrion crow
      (Corvus cornix). In addition, E. hellem was found for the first time in birds
      from the Anseriformes and Gruiformes orders. Whereas E. intestinalis was
      disclosed for the first time in the domestic goose (Anser anser f. domestica),
      red ruffed lemur (Varecia variegata rubra) and the ring-tailed lemur (Lemur
      catta), while the black lemur (Eulemur macaco flavifrons), mongoose lemur
      (Eulemur mongoz) and the Visayan warty pig (Sus cebifrons negrinus) were first
      found to carry E. bieneusi. The mammal species that were found to carry E.
      bieneusi and E. intestinalis are included in The IUCN Red List of Threatened
      Species. The results of the present study are significant from an epidemiological
      point of view. The wild, livestock and zoo animals that were found to carry
      microsporidia live in different conditions, and thus their role as animal
      reservoirs for these dangerous pathogens varies. Waterfowl birds may be the main
      source of contamination of surface waters with E. hellem spores and the
      protection of surface waters is virtually impossible. Moreover, isolates of E.
      hellem from mute swans have SSU rRNA sequences identical to E. hellem genotype
      reported 10 years ago in HIV-positive patient in USA (GenBank Accession no.
      L19070). This result indicate that E. hellem from mute swans can be a potential
      source of infection for humans. The contamination of the human environment with
      microsporidian spores infectious to humans is also facilitated by farm and
      synanthropic birds, because E. hellem and E. intestinalis were found in farms
      pigeons, domestic goose and the carrion crow. These birds can also be the source
      of infectious for breeders and ornithologists. The occurrence of microsporidiosis
      in animals kept in zoological gardens may constitute a deadly hazard not only for
      the animals themselves, but also for zoo personnel and visitors. The
      identification of animal reservoirs of E. hellem, E. intestinalis and E. bieneusi
      in Poland points to the possibility of infection of humans. The results of the
      present study have shown that the FISH technique, although time-consuming, is
      very sensitive, not overly costly and--what is of prime importance--it enables
      identification of microsporidian species, and therefore should be used for
      diagnosing microsporidiosis in humans and animals.

PMID- 19579790
TI  - [Investigations on the biology of nematodes Elaphostrongylus cervi and
      epizootiology of elaphostrongylosis].
AB  - Elaphostrongylus cervi is a parasite of the family Protostrongylidae, occurring
      in cervids in Eurasia. This nematode has hitherto been recorded in some woodland
      areas in Poland. The current distribution of E. cervi in Poland was studied in
      the frames of the presently reported thesis. The above-mentioned nematode was
      found in deer in eight additional voivodeships, and in all thirteen forest
      management units examined. The prevalence values ranged from 66.7% to 100%. The
      above facts justify the statement that that E. cervi is a common parasite species
      in Poland. The dynamics of the larval shedding (L I) by deer was monitored and it
      turned out that there were two peaks--the first in February and the second in
      December. The identity of the intermediate hosts--terrestrial snails--has been
      established, as well as the prevalence and the infection intensity of their
      natural infections. The intermediate hosts of E. cervi are Succinea putris,
      Bradybena fruticum, Perforatella bidens, and Zonitoides nitidus. It was
      determined that the prevalence of snails, S. putris, infected with E. cervi
      larvae maintained a constant level from June to August and it decreased in
      September and October. Snails, B. fruticum, showed the highest prevalence in July
      -and it decreased in subsequent months. In the case of P. bidens the prevalence
      of E. cervi infection was the lowest in August, and than it increased, to reach
      the highest value in October. The prevalence of spontaneous infections of
      different snail species ranged from 7.6% to 20.6%. For the first time the highest
      prevalence of spontaneous infection was found in P. bidens. Till now the most
      infected species of snail has always been S. putris. The highest intensity of
      infection--242 larvae--was found in B. fruticum, and little lower--202 in S.
      putris. In two other species the intensity ranged from 1 to 23 larvae. The most
      significant role in spreading of E. cervi in the Bialowieza Forest is performed
      by S. putris and B. fruticum, because of their high abundance and P. bidens,
      because of their highest infection intensity. Also the penetration of the first
      stage larvae of E. cervi into the intermediate host and their development there
      throughout the third infective stage were studied. The first stage larvae of E.
      cervi enter the body of snail through the muscle of foot. The period of their
      development to the second stage is 7 to 9 days, and to the third stage is 21 to
      28 days. E. cervi is a parasite that under intensive infections is very dangerous
      for domestic ruminants in which in evokes neurological symptoms or even death.
      Because huge numbers of E. cervi larvae are shed by dear into the environment,
      homeothermic vertebrates, birds and wild boars can accidentally infect themselves
      with infective larvae of this parasite. To explain the course of such infections,
      fish, chickens, and Vietnamese pigs were experimentally infected. In fish and
      chickens the infective larvae of E. cervi were not able to cross the intestinal
      barrier, arrested their development, and were digested. Infected pigs produced no
      clinical symptoms of the infection. In those animals larvae were retained in
      mesenteric lymphatic nodes and were not able to cross the mesenteric barrier.
      None of the experimentally infected animals became paratenic hosts and their meat
      poses no threat to human health.

PMID- 19579791
TI  - [47. Day of medical parasitology "Toxoplasmosis: clinical course, diagnostics and
      therapy; other problems concerning mycology and parasitology"].

PMID- 19579792
TI  - [Conference "Tropical and parasitic diseases"].

PMID- 19579793
TI  - Influence of conformational antibodies on dissociation of fibrillar amyloid beta
      (A beta 1-42) in vitro.
AB  - Many neurodegenerative diseases result due to the accumulation of misfolded
      proteins as amyloid fibrils. Although the protein components of these fibrils
      from different disease states differ considerably, they appear to share common
      structure. Among these conformational disorders, Alzheimer's disease (AD) and
      prion diseases exhibit significant overlap in their mechanism of pathogenesis.
      The present report demonstrates that antibodies directed against the prion
      protein repeat motif, Tyr-Tyr-Arg motif, recognize recombinantly expressed human
      amyloid beta (A beta) aggregates in enzyme linked immunosorbent assay. In
      addition, these antibodies dissociate the preformed aggregates of A beta in
      vitro. These findings illustrate an important property of conformation dependent
      antibodies viz., they specifically recognize the protein deposits associated with
      pathology and not the protein in normal tissue. These antibodies may benefit the
      development of approaches towards prevention and treatment of protein misfolding
      diseases.

PMID- 19579794
TI  - Lipid profile changes in mouse gastrocnemius muscle after denervation and beta
      adrenoceptor stimulation.
AB  - Denervation results in the accumulation of total lipids (94.68%), phospholipids
      (190.94%), cholesterol (31.82%) and triglycerides (30.86%) within 30 days in
      gastrocnemius muscle of adult mice. The treatment of denervated mice with beta
      agonist isoproterenol (60 mg kg(-1) day(-1) for 30 days, orally) does not inhibit
      the increased lipid biosynthesis induced by the loss of neural supply to
      gastrocnemius muscle. The denervated gastrocnemius muscle shows 61.87, 133.14,
      40.27 and 16.46% more total lipids, phospholipid, cholesterol and triglyceride
      contents respectively as compared to normal innervated muscles even after the
      drug administration but it maintains significantly low levels of lipids as
      compared to untreated denervated mice.

PMID- 19579795
TI  - Effect of excessive cholesterol and lipopolysaccharide on cerebellar neuronal
      cells in in vitro and protective role of anti-inflammatory drugs.
AB  - The present work was carried out to elucidate the role of NSAIDs, PPARg agonist
      and HMG CoA inhibitor on cholesterol and lipopolysaccharide (LPS) induced
      neurodegeneration. The cerebellar, neuronal cells were exposed to cholesterol (10
      and 50 microg/ml), LPS (1 ng/ml) or both. Neuroprotective effect of ibuprofen,
      rofecoxib, simvastatin and pioglitazone was assessed by measuring the neuronal
      loss, MTT dye assay, nitric oxide, LDH and lipid peroxide measurement. The
      results indicated that incubation of cholesterol and LPS showed less synaptic
      connections, neurite outgrowth and cell shrinkage as compared to normal
      cerebellar cells. Significantly decreased survival cells count along with
      increased LDH, lipid peroxide and nitrite levels were observed in the cells that
      confirmed neurodegeneration with cholesterol and LPS challenge. In comparison to
      individual toxins (LPS or cholesterol), combination of LPS and cholesterol
      produced more deleterious effect indicated synergistic effect of toxins.
      Interestingly, in comparison to LPS, cholesterol produced significantly low level
      of nitrites, LDH and lipid peroxides which indicated excessive cholesterol might
      not influence radical generation directly and might be a secondary effect. Among
      the drugs studied, NSAIDs showed better effect indicated inflammatory mediator
      response played vital role in cholesterol and LPS induced neurodegeneration.
      Simvastatin demonstrated moderate neuroprotective effect. It could be concluded
      that excessive cholesterol might produce cell death and led to release of
      nitrites and other cytokines. NSAIDs had better neuroprotective activity than
      simvastatin that produced moderate effect.

PMID- 19579796
TI  - Mouse acquired HPV tumor using dorsal skin-fold window chamber.
AB  - Human papillomavirus (HPV) plays important role in developing several types of
      cancer especially cervical cancer. In order to understand the viral pathogenesis,
      the animal model of HPV infection is very necessary. This communication reports
      establishment of an animal model carrying implanted HeLa cells, a human cervical
      cancer cell line via dorsal skinfold window chambers. Nude mice were divided into
      4 groups; each group contained different amount of HeLa cells, 2.5 x 10(5), 5 x
      10(5), and 1 x 10(6) cells, and cell free medium (control), respectively. The
      results showed that even using the low number of HeLa cells (2.5 x l0(5)), the
      tumor microvasculature was developed at 2 weeks after implantation with the
      enlarged tumor margin which then progressed to tumor mass in the following week.
      The existing tumor was confirmed to be HeLa-cell type by PCR, in situ
      hybridization, and HPV genotyping. By using linear regression analysis, it
      indicated that means of tumor size from each group significantly increased in
      relation to number of HeLa cells used (R2 = 0.98, y = 0.1171x + 4.35). This mouse
      model will be useful for the further HPV studies particularly anti-cancer drugs
      efficacy.

PMID- 19579798
TI  - Protective effects of Petroselinum crispum (Mill) Nyman ex A. W. Hill leaf
      extract on D-galactose-induced oxidative stress in mouse brain.
AB  - With an aim to examine the effect of ethanolic extract of P. crispum (Parsley)
      leaves on the D-galactose-induced oxidative stress in the brain of mouse, the
      activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione
      peroxidase) involved in oxygen radical (OR)-detoxification and antiperoxidative
      defense were measured in conjunction with an index of lipid peroxidation in
      mitochondrial fraction of various regions of the mouse brain. A significant
      decrease in superoxide dismutase and glutathione peroxidase activity was observed
      in D-galactose-stressed mice, while catalase activity was increased. Treatment of
      D-galactose-stressed mice with the ethanolic extract of P. crispum showed
      protection against the induced oxidative stress in brain regions. Concentration
      of thiobarbituric acid-reactive product was greatly elevated in D-galactose
      stress-induced mice and was significantly reduced in the brain regions of these
      mice upon treatment with P. crispum. It is postulated that parsley shows a
      protective effect against mitochondrial oxidative damage in the mouse brain.

PMID- 19579797
TI  - Biochemical effects of feeding soft drink and ethanol.
AB  - This work was undertaken to study whether consumption of alcoholic beverage mixed
      with soft drinks could reduce the metabolic effect caused by ethanol. When 24 hr
      fasted rats were intragastrically fed rum (with 40% ethanol) diluted (1:1) with
      water, 3.0 ml (0.5 g ethanol) per 100 g body weight and sacrificed 12 hr later in
      fasting condition, exhibited higher levels of triacyl glycerol, glucose, total
      cholesterol, high density lipoprotein (HDL), aspartate amino transferase (AST),
      alanine amino transferase (ALT) and alkaline phosphatase (ALP) in serum, higher
      levels of total cholesterol, triacyl glycerol and thiobarbituric acid reactive
      substances (TBARS) in both liver and kidneys, and lower levels of serum albumin.
      When fasted rats were fed 3.0 ml soft drink (0.31 mg caffeine), they showed
      increased levels of triacyl glycerol, glucose, ALT and ALP in the serum, TBARS in
      liver and kidneys, triacyl glycerol and total cholesterol in kidneys and lower
      levels of serum albumin. Soft drink feeding did not reduce serum total
      cholesterol but reduced HDL levels. Also soft drink did not alter liver lipids.
      When a mixture of 1.5 ml diluted rum (0.25 g ethanol) and 1.5 ml soft drink
      (0.154 mg caffeine) were fed to the fasted rats, the serum parameters increased
      similar to rats fed rum only except that total cholesterol and HDL cholesterol
      were unaltered. TBARS in kidneys and liver were also increased but triacyl
      glycerol levels were not altered. Thus feeding ethanol with soft drink does not
      reduce the metabolic effects of ethanol but it will prevent ethanol induced serum
      HDL cholesterol rise.

PMID- 19579799
TI  - Anti-tumor studies with extracts of Calotropis procera (Ait.) R.Br. root
      employing Hep2 cells and their possible mechanism of action.
AB  - Anti-tumor potential of root extracts of Calotropis procera: methanolic extract
      (CM), hexane extract (CH), aqueous extract (CW) and ethylacetate extract (CE) and
      its possible mechanism against Hep2 cancer cells has been investigated. Cellular
      proliferation activities were assayed by tetrazolium bromide (MTT) colorimetry.
      Morphological changes of cancer cells were observed under inverted microscope and
      cell cycle parameters were determined by flow cytometry following propidium
      iodide staining. Treatment with the extracts at various doses of 1, 5, 10 and 25
      microg/ml revealed that CM, CH and CE possessed cytotoxicity, whereas CW did not
      have cytotoxic effect. CE (10 microg/ml) showed strongest cytotoxic effect
      (96.3%) on Hep2 at 48 hr following treatment, whereas CM and CH showed
      cytotoxicity of 72.7 and 60.5%, respectively. Extract-treated cells exhibited
      typical morphological changes of apoptosis. Results of flow cytometric analysis
      clearly demonstrated that root extracts initiated apoptosis of Hep2 cells through
      cell cycle arrest at S phase, thus preventing cells from entering G2/M phase.
      Results of the study indicate that the root extracts of C. procera inhibit the
      proliferation of Hep2 cells via apoptotic and cell cycle disruption based
      mechanisms.

PMID- 19579800
TI  - Ethanolic extract of Clerodendrum violaceum Gurke leaves enhances kidney function
      in mouse model of malaria.
AB  - Evaluation of the effects of daily oral administration of ethanolic extract of C.
      violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function
      indices of uninfected and Plasmodium berghei-infected mice was done on days 3, 8
      and 14 post-infection. The indices studied include serum urea and creatinine
      concentrations with the specific activities of alkaline phosphatase, aspartate
      aminotransferase and alanine aminotransferase in the kidney. Treatment of P.
      berghei-infected mice with ethanolic extract of C. violaceum leaves (13 mg/kg
      body weight) for 5 days was able to ameliorate significantly the alterations in
      the various parameters observed in infected untreated mice, comparing favourably
      with chloroquine treatment in most cases. Administration of extract to uninfected
      mice had no significant effect on both serum and kidney parameters compared to
      the uninfected control. The results suggest that the ethanolic extract of C.
      violaceum leaves does not adversely affect kidney function at the dose used in
      traditional medicine for the treatment of malaria but rather enhances it.

PMID- 19579801
TI  - Luteolin ameliorates ferric nitrilotriacetic acid induced renal toxicity and
      tumor promotional response in rat.
AB  - Ferric nitrilotriacetic acid (Fe-NTA) (9 mg Fe/kg body weight, i.p.) caused
      significant depletion in the detoxification and antioxidant enzyme armory with
      concomitant elevation in renal lipidperoxidation, serum toxicity markers viz.
      creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine
      decarboxylase activity and [3H] thymidine incorporation into renal DNA in wistar
      rats. However, pretreatment of animals with luteolin (10 and 20 micromol/kg body
      weight) for 7 consecutive days resulted in significant decrease in above
      parameters level. Renal glutathione content, glutathione metabolizing enzymes and
      antioxidant enzymes were also recovered to significant level. The enhanced
      reduced glutathione level and enzyme activities involved in xenobiotic metabolism
      and maintaining antioxidant status of cells is suggestive of a chemopreventive
      efficacy of luteolin against Fe-NTA mediated oxidative stress, toxicity and cell
      proliferation response in rats.

PMID- 19579802
TI  - Effects of microinjection of angiotensin II and captopril into nucleus accumbens
      on morphine self-administration in rats.
AB  - With an aim to investigate the effects of injection of angiotensin II (Ang II)
      and captopril into the nucleus accumbens (NAC) on morphine self-administration,
      male Wistar rats were first trained to receive small pellets of food by pressing
      the active lever in self-administration apparatus. The animals, divided into 4
      groups (saline, morphine, captopril and Ang II) were placed in self
      administration apparatus and were allowed to self-administer morphine (0.5 mg per
      infusion all test groups) or saline (saline group) during consecutive days, for 2
      h/sessions. Captopril (30 microg) and Ang II (0.25 nM) were injected into NAC in
      the corresponding groups before each session. In morphine group, the number of
      active lever pressing was significantly higher than passive during all 5 days and
      was also significantly higher than saline group. In captopril group, there were
      no significant differences between the number of active and passive lever
      pressings. However, the number of active lever pressing was significantly lower
      than morphine group. The results highlight the interaction between captopril and
      opioid system in NAC.

PMID- 19579803
TI  - Ethosomes: a novel delivery system for antifungal drugs in the treatment of
      topical fungal diseases.
AB  - Aim of this work was to prepare and characterize fluconazole (FLZ) encapsulated
      ethosomes, incorporate it in suitable dermatological base, and asses its
      comparative clinical efficacy in the treatment of Candidiasis patients against
      liposomal gel, marketed product and hydroethanolic solution of the drug. Drug
      encapsulated ethosomes and liposomes were prepared and optimized by "Hot" method
      technique and lipid film hydration technique. Vesicular carriers were
      characterized for % entrapment efficiency, particle size and shape, in vitro drug
      diffusion study, mean % reduction in dimension of Candidiasis lesion and
      stability study by using suitable analytical technique. Vesicle size and drug
      entrapment efficiency of the optimized ethosomes and liposomes were found to be
      144 +/- 6.8 nm and 82.68% and 216 +/- 9.2 nm and 68.22% respectively. Microscopic
      examinations suggest ethosomes to be multilamellar spherical vesicles with a
      smooth surface. The differential scanning calorimetry results suggest high
      fluidity of the ethosomes than liposomes. In vitro drug diffusion studies
      demonstrated that % drug diffused from ethosomes was nearly twice than liposomes
      and three times higher than the hydroethanolic solution across rat skin. From the
      clinical evaluation, the developed novel delivery system demonstrated enhanced
      antifungal activity compared to liposomal formulation, marketed formulation and
      hydroethanolic solution of the drug.

PMID- 19579804
TI  - An improved method for staining kinetochores of human chromosomes.
AB  - An improved method, which exhibited simultaneously clearly kinetochores and the
      nucleolar organizer regions of human chromosomes by pretreating of human
      metaphase chromosomes with HCl and NaOH, followed by staining with silver nitrate
      and visualizing using ammoniacal silver, is described in the present
      communication. It has important role for analysis of kinetochore variation,
      mechanism of chromosomal non-disjunction as well as identification of fuctional
      active centromeres.

PMID- 19579805
TI  - Comparative potential of modified indigenous, indigenous and commercial ELISA
      kits for diagnosis of Mycobacterium avium subspecies paratuberculosis in goat and
      sheep.
AB  - In the present study, modified indigenous ELISA kit (kit 1) was compared with
      indigenous ELISA kit (kit 2) and commercial ELISA kit (kit 3) for its sensitivity
      and specificity with respect to faecal culture for diagnosis of Johne's disease
      in goats and sheep under natural conditions. Of the 64 positive animals, serum of
      42.1, 48.4 and 18.7% animals yielded positive infection in kit 1, 2 and 3,
      respectively. Specificity of kit 1 (95.1%) was maximum followed by kit 3 (93.7%)
      and kit 2 (83.4%). Kit 1 showed superior diagnostic potential than the other two
      kits. Kit 1 may be used as single screening test regimen for diagnosis of MAP
      infection in the population of goats and sheep in India.

PMID- 19579806
TI  - Professor Tadeusz Orlowski -- the founder of Polish nephrology.

PMID- 19579807
TI  - Professor Tadeusz Orlowski: in memory of an outstanding doctor and a leading
      personality in the scientific life.

PMID- 19579808
TI  - My remembrance of Professor Tadeusz Orlowski.

PMID- 19579809
TI  - Involvement of Professor Tadeusz Orlowski in the development of artificial organs
      in Poland.

PMID- 19579810
TI  - Tadeusz Orlowski and his Tatra trails.

PMID- 19579811
TI  - Surgical removal of the pancreas with one-step autotransplantation of isolated
      Langerhans islets into the hepatic portal system in the pig.
AB  - INTRODUCTION: Autotransplantation of isolated Langerhans islets is regarded as
      the only way to prevent iatrogenic diabetes in patients who had been scheduled
      for pancreatectomy due to painful chronic pancreatitis. A sufficient number of
      Langerhans islets capable of secretory activity need to be transplanted to
      maintain normoglycemia after the surgical procedure. In order to optimize all
      stages, including collection, storage, isolation and transplantation of
      pancreatic islets, a reproducible animal-based experimental model should be
      developed before a new method is introduced into clinical practice. OBJECTIVES:
      The aim of the present study was to develop a reproducible autogenic model-based
      method for collection, conservation and isolation of porcine pancreas so that
      transplantation of isolated pancreatic islets could be performed and
      postoperative normoglycemia achieved. MATERIAL AND METHODS: Pigs were subjected
      to total pancreatectomy with simultaneous splenectomy and without removal of the
      duodenum. The collected pancreas was stored in the University of Wisconsin
      solution with the addition of pentoxifylline (PTX) until the isolation procedure
      (<4 hours). Efficacy of isolation was evaluated based on the number, quality and
      viability of obtained islets. Following autotransplantation into the liver,
      secretory activity of the islets was assessed intravitally by serum glucose
      monitoring. RESULTS: The islet yield per gram of pancreas was 1452 (standard
      deviation [SD] +/- 125) for the PTX group and 384 (SD +/- 115) for the control
      non-PTX group (p<0.01). Viability of islets for individual isolations did not
      reveal any statistically significant differences between groups and was estimated
      at 85-93%. Three out of five animals demonstrated normoglycemia with features of
      neoangiogenesis in the islets transplanted into the liver, which was confirmed by
      histological examination. One animal developed hyperglycemia up to 430 mg/dl, and
      histological image showed intensive apoptosis and degranulation in the
      transplanted islets. CONCLUSIONS: Efficacy of the isolation method was confirmed
      by achieving normoglycemia after autotransplantation of pancreatic islets into
      the liver, while histological examination showed hepatic vascularization to be
      the most appropriate location for an autogenic graft. PTX presence in the
      preserving solution for the pancreas storage produced the cytoprotective effect,
      which directly correlated with the islet yield.

PMID- 19579812
TI  - The kinetics of water transperitoneal transport during long-term peritoneal
      dialysis performed using icodextrin dialysis fluid.
AB  - INTRODUCTION: Dialysis fluid containing icodextrin is used in patients on
      peritoneal dialysis (PD) because of its significant ultrafiltration properties.
      The use of the fluid in treating patients with congestive heart failure resistant
      to diuretics has also been reported. OBJECTIVES: The aim of the study was to
      evaluate water peritoneal transport during a 16-hour dialysis exchange performed
      using icodextrin-containing dialysis fluid. PATIENTS AND METHODS: Eleven
      clinically stable patients were enrolled in the study (5 women and 6 men; mean
      age, 50.4 +/- 18.3 years), treated with PD for 26.9 +/- 22.4 months. Water
      transperitoneal transport was evaluated using a modified version of Babb
      Randerson-Farrell thermodynamic model of membrane transport with human albumin
      marked with iodine as the marker of intraperitoneal volume. Based on blood and
      dialysate samples collected during the 16-hour dialysis exchange, the
      intraperitoneal volume of dialysate and dialysate reverse absorption were
      calculated. RESULTS: There were no clinical complications associated with the use
      of icodextrin fluid during the study. A significant increase in intraperitoneal
      volume of dialysate (950 ml on average) compared to the initial value was
      observed in the whole group at the 16th hour of the exchange. CONCLUSIONS: The
      study demonstrated that dialysis fluid with icodextrin ensured effective
      ultrafiltration during a 16-hour dialysis exchange. This indicates its potential
      usefulness in the treatment of patients with severe congestive heart failure with
      or without coexisting end-stage renal disease.

PMID- 19579813
TI  - Isolation, banking, encapsulation and transplantation of different types of
      Langerhans islets.
AB  - INTRODUCTION: The discovery of a cure for diabetes is a dream of many medical
      researchers. The transplantation of Langerhans islets is a potential treatment of
      choice for patients with type 1 diabetes as a source of endogenous insulin for
      the recipient. OBJECTIVES: The aim of the experiment was to transplant Langerhans
      islets without immunosuppression. To protect the grafts against transplant
      rejection, semipermeable membranes could be used. MATERIAL AND METHODS:
      Langerhans islets were isolated from rats and pigs and immunoisolated by
      encapsulation in alginate-protamine-heparin (APH) or alginate-poly-L-lysine
      alginate (APA) membranes. Islets were pooled in a controlled manner. Tests for
      cryopreservation and biocompatibility were also performed. RESULTS: The capsules
      coated with APH are more resistant than the capsules coated with APA. After
      transplantation of the islets immunoisolated with APA, euglycemia is maintained
      longer than after transplantation of the islets immunoisolated with APH.
      Microencapsulation protects the islets from destruction by the host. CONCLUSIONS:
      It is feasible to treat experimental diabetes by transplantation of encapsulated
      Langerhans islets without immunosuppression.

PMID- 19579814
TI  - Calcineurin inhibitor sparing immunosuppressive regimens in kidney allograft
      recipients.
AB  - Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, have had a potent
      impact on the success of organ transplantation. However, the nephrotoxicity
      associated with CNI can cause renal dysfunction, which is an independent risk
      factor for graft loss and mortality after kidney transplantation (KTx). Thus, the
      search for an optimal immunosuppressive therapy continues to be crucial in KTx.
      Strategies to limit CNI exposure include CNI minimization, avoidance, and
      withdrawal. We conducted a literature review (PubMed, Medline) on this issue.
      Maximum reduction in CNI is associated with a modest improvement in renal
      function; however, the kidney damage is observed as long as CNIs are maintained.
      Avoidance of CNI is associated with high acute rejection rates. CNI withdrawal
      may be the optimal strategy because it reduces early immunologic graft injury
      after KTx, particularly when CNI withdrawal is initiated before irreversible
      renal damage. These strategies seem feasible with mycophenolate acid, sirolimus
      and induction therapy with interleukin-2 receptor antibodies as concurrent
      immunosuppressants.

PMID- 19579815
TI  - Allogeneic transplantation of isolated islet cells in clinical practice.
AB  - The only clinically acceptable radical treatment for patients with insulin
      dependent diabetes mellitus is a whole pancreas transplantation, or alternatively
      an infusion of isolated islet cells into the hepatic portal venous system.
      Allogeneic transplantation of isolated islet cells is a procedure used only in a
      highly specific group of recipients, whereas intensive insulin treatment still
      remains the best therapy to achieve glycemia control in most patients with type 1
      diabetes. Two groups of allograft recipients should be taken into consideration
      when scheduled for islet cell transplantation. The first group comprises
      allogeneic kidney recipients with a stabilized graft function for >6 months who
      receive chronic immunosuppression and require transplantation for end-stage renal
      disease caused by diabetic nephropathy. The second group consists of patients
      with unsatisfactory glycemic control despite insulin therapy, life-threatening
      hypoglycemic episodes and a rapid progression of long-term complications. Despite
      increasingly beneficial outcomes, islet cell transplantation has several
      limitations. Maintaining normoglycemia without exogenous insulin administration
      and appropriate selection of immunosuppressive agents to prolong graft survival
      are the major challenges. The aim of related studies has been to optimize all
      phases of islet cell transplantation in order to achieve total insulin
      independence and prolong graft survival.

PMID- 19579816
TI  - Immunosuppressive therapy in glomerular diseases: major accomplishment of Tadeusz
      Orlowski and his school.
AB  - Glomerulopathies are the third most common cause of end-stage renal failure.
      Immunosuppressive treatment of glomerulonephritis in a systematic way was
      introduced in Poland by Professor Tadeusz Orlowski in the early 1960s. The
      studies were conducted at the First Department of Medicine and at the
      Transplantation Institute of the Medical Academy in Warsaw in the years 1962
      1988. This paper critically reviews the results of studies on the use of
      combined, triple-drug (prednisone/chlorambucil/azathioprine), immunosuppressive
      protocol in various pathological forms of glomerulopathies. We conclude that
      immunosuppressive protocols pioneered by Tadeusz Orlowski continue to be the
      backbone of the treatment of glomerulonephritis, especially the one with
      nephrotic syndrome, progressive impairment of kidney function and poor prognosis.

PMID- 19579817
TI  - [The disciples of Goroji Nakagawa and their practice of vaccination in the
      northern area of Japan].
AB  - Goroji Nakagawa (1768-1848), who returned to Japan from Siberia in 1812,
      introduced Jennerian vaccination. At present three persons have been identified
      as his disciples. Yuzo Shiratori (1813?-1851) was the most senior among them. He
      was the second son of a wealthy merchant in Hakodate and learned medicine under
      Teisai Hino (1797-1850), a leading physician in Kyoto. It is unknown when he came
      back to Hakodate; however, Nakagawa taught him the Russian method of vaccination
      in about 1840. Shiratori went to Akita of the Satake domain to learn medicine
      further and there he practiced vaccination to prevent smallpox epidemics. Because
      his method was recognized as being effective, the Satake domain accepted to
      employ it formally and asked him to teach the method among domain physicians in
      the period from about 1841-1844. Details of biographies of the other two
      disciples, Keisaku Takagi and Kozen Sakurai, as well as their practical method of
      vaccination, have still not yet been clarified; however, it has been established
      that they used it with many people of Matsuma-e and neighboring areas. In
      September of 1849 Hino failed to successfully vaccinate on seven consecutive
      occasions using cow pox crusts obtained from Nagasaki, but he was finally
      successful in the last trial, using the Russian method as informed by Shiratori.
      Thus Hino could distribute much lymph among many physicians in the west half of
      Japan. Considering the above matters, we can conclude that Nakagawa's method had
      a significant influence on the history of Jennerian vaccination in Japan.

PMID- 19579818
TI  - [On the lecture on the history of anatomy which Lu Xun heard in Sendai].
AB  - In "Fujino Sensei," Lu Xun wrote that in his first lecture on anatomy, osteology
      Professor Fujino talked about the history of anatomy in Japan; although Lu Xun's
      extant lecture notes do not show any mention of Fujino's comments on the history
      of anatomy. However, since the lecture notes of senior students mention the
      history of anatomy, we do not find any reason to assume that Lu Xun did not hear
      about the history of anatomy in the lecture. Furthermore, the timetable of
      lectures indicates that the first lecture of anatomy was attributed to Professor
      Fujino. It is concluded that the description of the first anatomical lecture in
      "Fujino Sensei" was written based on Lu Xun's actual experience. The lecture on
      the history of anatomy which Lu Xun heard was made by Professor Fujino; probably
      based on a lecture by Professor Shikinami which was recorded in the notes of
      Saito Ryusho, a student who was three years senior to Lu Xun.

PMID- 19579819
TI  - [The position of nursing at the beginning of the Meiji Era: the elucidation of
      the original source of "Kango-Kokoroe," translated by Dr. Yunei Ota, and a
      comparative study of the original and translated versions].
AB  - In this paper, through a detailed comparison between a translated book on nursing
      and its original American source, I examine the position of nursing in the
      mentality of a Japanese doctor at the beginning of the Meiji Era. In 1877, Dr.
      Yunei Ota published a translated version of a book on nursing titled "Kango
      Kokoroe." The original book, titled "A Universal Formulary, 3rd. Edition," was
      written by R. E. Griffith and published in 1873. Further, I show that Yunei Ota
      translated a part of its introduction. These two books differ in terms of their
      target audiences and purposes for publication. From the viewpoint of the doctor
      nurse relationship, Yunei Ota described his unique mentality in his translation;
      that is, he stressed the importance of nursing by stating that nurses were for
      doctors as wings were for birds. This mentality was rarely found in the original
      American book. Moreover, Yunei Ota did not make a literal translation; instead,
      he selected, added, and deleted contents from the book in keeping with a
      practical standpoint. Yunei Ota recognized that nursing was an indispensable part
      of medical treatment and he advocated the necessity of nursing education before
      systematic nursing education had been established in Japan.

PMID- 19579820
TI  - [Research on "Chikushi-Kou Zakki": the travel diary for Nagasaki of Sosen
      Nakashima].

PMID- 19579821
TI  - [Lectures on the history of anatomy held at the Sendai Medical School in 1900 and
      1901].

PMID- 19579822
TI  - [Retrospective aspect of modern pharmaceutical studies in Japan and memory of my
      life working in pharmaceutical science].

PMID- 19579823
TI  - [The history of pharmacy in Korea].
AB  - The history of pharmacy in Korea from the era 'Dangun Mythology' to the present
      day was reviewed briefly with special emphases on the beginning of pharmaceutical
      education, the introduction of modern pharmaceutical education, the establishment
      of modern educational institutions, the evolution of a new 6-year pharmaceutical
      education program, and the separation of drug prescribing and dispensing.

PMID- 19579824
TI  - Modern pharmacy in India. A historical perspective.

PMID- 19579825
TI  - [Consideration of the achievements of successive presidents of the Japan
      Pharmaceutical Association in the post-war Showa period--their thoughts and steps
      for establishing practice rights].
AB  - The system of separating the dispensing and prescribing of drugs was legally
      established in 1956 on the recommendation of the American Pharmaceutical
      Association mission to Japan in 1949. However, serious disagreements between
      medical and pharmaceutical practitioners impeded implementation of the system,
      and the separation practice was not initiated until 1975 when the Japan
      Pharmaceutical Association and the Japan Medical Association established friendly
      relations. The system finally took root in the 1990s, and the Japan
      Pharmaceutical Association has since continued to further improve the system.

PMID- 19579826
TI  - [The transition of amino acid drug development for 50 years in Japan (1)--amino
      acid parenteral fluid].
AB  - Twenty kinds of alpha-amino acids that form the constituents of proteins in
      mammalian tissues are all L-form with the exception of glycine. These proteins
      consist of both dispensable and indispensable alpha-amino acids, and play an
      important role as nutrients. The artificial mixtures of these alpha-amino acids
      are also important as ethical drugs. The history of alpha-amino acid parenteral
      fluid is not as long as one might think in terms of its clinical applications.
      The first publication of clinical data on the subject only appeared in 1944. In
      Japan, the first product using alpha-amino acid solution made from casein protein
      entered the market in 1950. In 1959, an alpha-amino acid solution produced from
      optically pure L-form was launched in Japan and became a pioneer in the field of
      artificial mixture solutions worldwide. From the 1960s, the amino acid industry
      has developed remarkably in Japan by means of chemically synthetic, enzymatic and
      microbial methodologies. Since then, most of the optically active alpha-amino
      acids have been easily obtainable, and the clinical uses of a-amino acid
      solutions using a variety of combinations have developed tremendously. From the
      1950s to the 1970s, most of the mixture solutions containing a large number of a
      amino acids were clinically developed for nutritional supplements. However, from
      the 1990s, amino acid solutions targeting diseases such as hepato-nephricpathy
      have increased, while new pediatric a-amino acid solutions are still being
      launched today. Since the year 2000, amino acid kit formulations with vitamins
      have been developed for convenient use in hospitals.

PMID- 19579827
TI  - [Research on the original plants of Xian Zhao Zi (Senshosi)].
AB  - Since the Heian period, Xian Zhao Zi (Senshosi) has been used as part of the
      ceremony believed to help in a healthy pregnancy and safe birth. The purpose of
      this report is to consider which plants are original Xian Zhao Zi plants. Past
      research lists certain plants as Xian Zhao Zi, but it was difficult to draw any
      conclusions.

PMID- 19579828
TI  - Regulation of the statements in the information on drug metabolizing enzyme in
      the package insert--the present regulation and its history in Japan, the U.S. and
      the U.K.
AB  - The information about a drug interaction is specified as a section which should
      be printed on the package insert in Japan, the U.S. and the U.K. In Japan, the
      information on drug metabolizing enzymes is described in the precautions for use
      in the package insert of many pharmaceutical agents following the incidence of
      the harmful effects of sorivudine. Since many elderly people suffer from two or
      more diseases as a result of aging and multiple pharmaceuticals are prescribed
      for them, the risk of drug interactions is increased. The therapeutic category
      where the most statements regarding drug metabolizing enzyme were in the package
      inserts, is hypnotics and sedatives, and anxiolytics; 100 out of 306 drugs
      include a statement about drug metabolizing enzymes. In the elderly aged 75 and
      over, regardless of whether the medicine is received in the hospital or by
      pharmacy preparation, in about 70 percent of the patients, three or more types of
      pharmaceutical agents are prescribed. Thus, although the information about the
      drug metabolizing enzyme is provided to the medical staff, in order to properly
      utilize the information, it is necessary to check whether the information about
      the same drug metabolizing enzyme is described in the package insert of the other
      pharmaceuticals that the patient is concurrently receiving. A means by which to
      quickly and easily retrieve the information about the drug metabolizing enzyme
      printed in the package is necessary and such a tool will be developed in the near
      future.

PMID- 19579829
TI  - Construction of the curriculum and lectures for the subject, "History of
      pharmacy" in Matsuyama University School of Pharmacy.
AB  - Matsuyama University School of Clinical Pharmacy started in the academic year of
      2006. After an obligatory subject, "The Outline of Pharmacy" in the spring
      semester, the elective course on pharmaceutical history is held with a 90-minute
      lecture a week for 15 weeks in the autumn semester of the first year for the
      students. The course consists of 4 parts as follows. The 15 consecutive lectures
      are carried out in the order of (1), (2), (3) and (4) and they are; (1)
      Pharmaceutical History in Japan, (2) Pharmaceutical History in the World, (3) The
      Specific Lectures:Infectious diseases and their treatment from the viewpoint of
      history, and (4) Introducing English Articles: "Highlights from the History of
      Medicine". However, in the present authors' opinion, pharmaceutical history from
      the beginning through the present days might fall roughly into 3 phases, namely
      the ages of superstition, experience and science with the occasional
      humanitarianism activities. We have been looking for a possible similar idea
      published elsewhere.

PMID- 19579830
TI  - [Similarities between Indian Hindu god Dhanvantari and Yakushi Buddha (Buddha of
      healing)].
AB  - The authors compared statues and figures of Buddha of Healing (Yakushi Buddha)
      with those of Dhanvantari god and Varuna god in India. Statues and figures of
      Ayurvedic God, Dhanvantari, are respected by Indian medical doctors, pharmacists
      and patients. Dhanvantari has the medicinal pot containing the rejuvenating
      nectar (Amrta). Therefore, it is most probably the case that the Yakushi Buddha
      in Japan originated from the Dhanvantari God in Ayurveda.

PMID- 19579831
TI  - [The origination of surgery (Kinso treatment) in Japan].
AB  - From the Nara period through to the end of the Heian and early Kamakura periods,
      the population of Japan grew by 50% thanks to increases in rice cultivation. Such
      expanded food production resulted in changes in the social structure providing
      opportunities to those in control of armed forces to become local feudal lords.
      Many wars fought in the process necessitated the development of treatment methods
      for Kinso (wounds caused by swords, spears, and similar weapons), to which
      Jinsoes (Buddhist monks/doctors that accompanied troops) attended, making
      extensive use of herbal medicine that had been developed by the people of the
      time. Many war commanders brought Jinsoes to battle fields, which became a custom
      during the Sengoku (warring) period. As many of the Jinsoes were well educated,
      they also served as entertainers to the commanders through their knowledge in Go
      or Renga (a game involving popular poetical verses). Their talents and training
      eventually resulted in many of the so called traditional arts including Noh,
      Kabuki, tea ceremony and earthenware production.

PMID- 19579832
TI  - [Questionnaires for pharmacies and pharmacists working in the hospitals built
      during the Meiji and Taisho periods in Japan].
AB  - In the previous paper, information about questionnaires for pharmacies and
      pharmacists in the 86 hospitals built during the Meiji and Taisho periods in
      Japan was reported. The histories of old pharmacies and pharmacists of the
      remaining 10 old hospitals were also reported in this paper.

PMID- 19579833
TI  - [The history of medicine and the World Wide Web].

PMID- 19579834
TI  - [The adventurous journey of Haydn's skull].

PMID- 19579835
TI  - [Natural or synthetic vitamin C? A new substance's precarious status behind the
      scenes of World War II].
AB  - Today, thousands of tons of vitamin C (l-ascorbic acid) is synthesized every year
      by the pharmaceutical industry. Synthetically produced vitamin C is widely
      accepted as having the same physiological effects as vitamin C isolated from
      natural sources. This is an important difference compared to the 1930s when
      vitamin C was synthesized for the first time. The identity of synthetic vitamin C
      with natural vitamin C had to be established. First of all, the scientific
      community had to accept that artificial I-ascorbic acid and natural vitamin C
      were chemically identical and had the same physiological effects. Second, other
      communities like food manufacturers, military health officials, and the broader
      public also had to be persuaded that these substances were equal. This article
      demonstrates how Hoffmann-La Roche, a Swiss pharmaceutical company and world
      leading producer of synthetic vitamins in the 20th century, tried to coax its
      adversaries into supporting artificial vitamin C. In doing so, synthetic vitamin
      C was naturalized in different ways. In the case of Switzerland during the Second
      World War era, the mentality of national defense and the quest for products
      supporting autarchy helped to convince perspective consumers. Thus in order to
      sell a new chemical substance, cultural meaning had to be attached to it.

PMID- 19579836
TI  - [Novel treatment possibilities for proximal caries].
AB  - So far approaches for caries treatment follow a dichotomized scheme: Non invasive
      options of primary and secondary prevention are contrasted to invasive treatment
      of caries lesions. Depending on the treatment philosophy of dentists and dental
      schools an early or late invasive treatment threshold is recommended. Sealing of
      proximal lesions as done in pit and fissures has only been established in some
      dental schools, so far. Moreover, infiltration of the enamel part of lesions
      could close the gap between preventive and invasive measures. Most of these novel
      treatment options for proximal surfaces are currently in the last stages of
      product development. With respect to the good clinical results of proximal
      sealing with conventional sealants, this regimen seems already be recommendable
      to hamper further lesion progression in clinical practice. Caries infiltration of
      lesions situated on proximal and other smooth surfaces might even be a more
      promising approach, if clinical studies corroborate the recent in vitro findings.
      All these novel limited invasive strategies might be suitable to complete the
      current dichotomized way of caries treatment.

PMID- 19579837
TI  - [The interdisciplinary fixed restoration of an edentulous maxilla with a marked
      resorption of the alveolar crest. A case report. Part II: the definitive
      restoration].
AB  - Different materials and methods can be used for edentulous maxillae
      rehabilitations. A precise fit between the implant and the framework is assumed.
      Hence, often implant suprastructures made by conventional lost wax techniques
      lack such a fit and a secondary modification is necessary. Alternatively the CNC
      milling technique provides implant frameworks with a passive fit made of titanium
      and recently also of zirconia. This article describes the fabrication of a fixed
      complete dental prosthesis supported by seven implants in an edentulous maxilla.
      Two prostheses were fabricated, one made of a titanium framework veneered with
      resin and one made experimentally of a zirconia framework veneered with ceramics.
      The clinical and technical steps are documented and discussed.

PMID- 19579839
TI  - [Rigorous organization in the time of pandemic influenza].

PMID- 19579838
TI  - [Interradicular course of the inferior alveolar nerve at the mandibular right
      third molar and monostotic fibrous dysplasia affecting the mandibular left third
      molar in the same patient. A case report].
AB  - To minimize the risk of intraoperative complications, a comprehensive
      radiological diagnostic work-up should be a routine procedure in oral surgery.
      This is especially true concerning possible damage to the inferior alveolar nerve
      during surgical removal of the third molars. The course and location of the nerve
      are best assessed when evaluating panoramic view images or cone beam CTs. The
      following case report demonstrates and discusses the importance of a thorough
      radiological evaluation before surgery, the problems raised by an interradicular
      course of the inferior alveolar nerve, and the finding of a monostotic fibrous
      dyplasia in the same patient.

PMID- 19579840
TI  - [Stroke, a calamity].

PMID- 19579841
TI  - [Stroke, a priority in care].

PMID- 19579842
TI  - [Interpersonal relations and unity in the care of strokes].

PMID- 19579844
TI  - [Preventing aggravation and recurrence after a stroke].

PMID- 19579843
TI  - [Multidisciplinary care of a patient].

PMID- 19579845
TI  - [Developing prevention and improving care after strokes ].

PMID- 19579846
TI  - [Innovations in care, with transient ischemic attacks as an example].

PMID- 19579847
TI  - [Nicole Jacquemin or promotion without intermission for nurses].

PMID- 19579848
TI  - [Installing oneself as a liberal nurse].

PMID- 19579849
TI  - [Accompanying and palliative care of patients with cancer and asthenia].

PMID- 19579850
TI  - [Scanners for securing the administration of chemotherapy].

PMID- 19579851
TI  - [Management of stress and the formation of nurses].

PMID- 19579852
TI  - [Knowing how the manage a person with problems of consciousness].

PMID- 19579853
TI  - [The art of nursing, portraits in the improvement of women and men].

PMID- 19579854
TI  - [Ethel Bedford Fenwick (1857-1947].

PMID- 19579855
TI  - [Methylphenidate. A drug for attention deficit disorders to be used with
      precaution].

PMID- 19579856
TI  - Italian performance in cancer research.
AB  - AIMS AND BACKGROUND: Italian performance in cancer research from 2000 to 2007 was
      assessed and compared to that of the other 19 wealthiest countries in the world
      which carry out the bulk of cancer research. METHODS: Performance was evaluated
      quantitatively as the number of publications in 125 journals indexed as
      'oncological' by Journal Citation Reports and qualitatively as the total impact
      factor (TIF). Number of publications and TIF were adjusted for the population and
      gross domestic product (GDP) of each country. The Scopus database was used as
      publication source. RESULTS: Italy ranked 5th, with the US ranking 1st, over the
      entire study period for number of cancer publications, which increased over that
      period. Italy ranked 4th in 2006-2007 for GDP-adjusted and 5th for population
      adjusted publication number, loosing ground in the GDP-adjusted ranking and
      gaining ground in the population-adjusted ranking over the study period. When the
      quality of research publications was considered, in 2006-2007 Italy was in 5th
      place for crude TIF (US 1st), in 4th place for GDP-adjusted TIF (Sweden 1st), and
      in 6th place for population-adjusted TIF (Sweden 1st). Over the study period,
      Italy was stable for crude and population-adjusted TIF but declined somewhat for
      GDP-adjusted TIF. CONCLUSIONS: Italy's performance in cancer research over the
      eight years to 2008 was better than expected considering its GDP and population.
      Nevertheless, the slight decline evidenced by the present study should induce
      scientists and policy makers to find ways to reverse the situation.

PMID- 19579857
TI  - Estimates of the incidence and prevalence of renal cell carcinoma in Italy in
      2002 and projections for the years 2007 and 2012.
AB  - AIMS AND BACKGROUND: Data on kidney cancer incidence and prevalence are not
      available on a national and regional level. We provided estimates of the number
      of incident and prevalent cases of kidney and renal cell cancer in Italy overall
      and in various regions in 2002 and gave projections for the years 2007 and 2012.
      METHODS: We derived annual numbers of incident cases combining mortality data
      provided by the World Health Organization and information on relative survival
      from kidney cancer and we subsequently derived 5-year prevalence by combining
      incidence with information on survival. We provided different projection
      estimates for the years 2007 and 2012 for incidence and prevalence, on the basis
      of various hypothetical scenarios, i.e., stable rates over time or steady falls
      by 1% per year. RESULTS: In 2002, there were about 8000 incident cases and 26,800
      prevalent cases of kidney cancer in Italy. Of these, approximately 6800 and
      22,750 were incident and prevalent cases of renal cell cancer, respectively. The
      most reliable estimate of incident kidney cancer cases in Italy over the period
      2007-2012 is likely to range between 7000 and 9000. Of these, between 6000 and
      8000 are renal cell cancer cases. The best estimate of prevalence of kidney
      cancer is between 20,000 and 34,000 cases and that of renal cell cancer between
      17,000 and 29,000 cases. CONCLUSIONS: Incidence and prevalence of renal cell
      cancer are likely to remain approximately stable between 2002 and 2007. Increased
      diagnostic attention due to widespread use of echography and other diagnostic
      techniques may, however, lead to earlier detection of kidney neoplasms and
      consequently to an apparent increase in the incidence of renal cell cancer.

PMID- 19579858
TI  - Incidence of invasive cervical cancer and direct costs associated with its
      management in Italy.
AB  - AIM AND BACKGROUND: Cervical cancer is the second most common cancer in European
      women aged 15-44 years. The aim of this study was to estimate the direct cost of
      managing invasive cervical cancer in Italy. METHODS: Data from the Italian
      Network of Cancer Registries were used to estimate the annual number of new
      cervical cancer cases. To assess the management costs, a typical management
      pathway for each FIGO (Federation Internationale de Gynecologie et d'Obstetrique)
      cervical cancer stage was derived from published guidelines. Data from the Modena
      Cancer Registry were used to estimate the proportion of patients by FIGO stage.
      This algorithm was combined with tariffs for outpatient and inpatient procedures
      to obtain a mean cost for each FIGO stage. RESULTS: An estimated 2,927 new cases
      of cervical cancer occurred in Italy in 2005 (crude incidence 9.7/100,000; world
      age-standardized incidence 6.0/100,000). The estimated numbers of new cases by
      FIGO stage were: FIGO I, 1,927; FIGO II, 556; FIGO III, 259; and FIGO IV, 185.
      Costs for the most frequent procedures were estimated as: Euro 6,041 for radical
      hysterectomy or other surgery; Euro 4,901 for radio-chemotherapy; Euro 1,588 for
      brachytherapy; and Euro 3,795 for palliative chemotherapy. Mean management costs
      for incident cases (including 10 years of follow-up) were estimated at: FIGO I,
      Euro 6,024; FIGO II, Euro 10,572; FIGO III, Euro 11,367; FIGO IV, Euro 8707; and
      Euro 5,854 for the terminal phase (1 month). The total direct management cost was
      estimated at Euro 28.3 million per year. CONCLUSIONS: This is one of the first
      studies to estimate the direct cost of treating patients newly diagnosed with
      invasive cervical cancer in Italy. Although according to current management
      pathways real treatment costs are likely to be underestimated, this information
      is necessary to design evidence-based vaccination policies able to harmonize
      primary and secondary prevention of cervical cancer.

PMID- 19579860
TI  - Primary pancreatic lymphoma.
AB  - AIMS AND BACKGROUNDS: Primary pancreatic lymphoma is non-Hodgkin lymphoma
      primarily involving the pancreas, which is rare in pancreatic diseases. The aim
      of this work is to summarize the diagnostic and therapeutic experience of primary
      pancreatic lymphoma. METHODS: We retrospectively reviewed the clinical data of 7
      cases of primary pancreatic lymphoma admitted to Huashan Hospital in the past 3
      years. Available English literature was also reviewed using the following terms:
      primary pancreatic lymphoma and pancreatic lymphoma. RESULTS: The literature
      review identified 157 additional cases, and a total of 164 cases had been
      analyzed. In this series, only 30% had a successful non-operative diagnosis. The
      curative rate of the surgery-adjuvant chemotherapy group was higher than that of
      the chemotherapy alone group. CONCLUSIONS: Obtaining specimens through surgery is
      an effective diagnostic tool. Surgical resection in combination with
      postoperative chemotherapy plays a therapeutic role.

PMID- 19579859
TI  - Is complete axillary dissection necessary for all patients with positive findings
      on sentinel lymph node biopsy? Validation of a breast cancer nomogram for
      predicting the likelihood of a non-sentinel lymph node.
AB  - AIM AND BACKGROUND: Axillary dissection in patients positive for sentinel lymph
      nodes is currently under discussion in the literature, since approximately only
      50% of such patients has metastases in the remaining lymph nodes. To identify
      patients at risk for non-sentinel lymph nodes metastases, a nomogram was
      developed by the Breast Service of the Memorial Sloan-Kettering Cancer Center.
      The aim of this study was to assess the nomogram's predictive accuracy in a
      population of Italian breast cancer patients in our hospital. MATERIALS AND
      METHODS: The system of calculation used as variables prognostic factors of breast
      cancer: pathologic size, tumor type and nuclear grade, lymphovascular invasion,
      multifocality, estrogen receptor status, method of detection of the sentinel
      lymph nodes metastases (frozen section, serial hematoxylin-eosin, routine
      hematoxylin-eosin, and immunohistochemistry), number of positive and number of
      negative sentinel lymph nodes. RESULTS AND CONCLUSIONS: To measure the
      discrimination of the nomogram, a receiver-operating characteristic curve was
      construed, and the area under the curve was calculated. However, the area under
      the curve was 0.72, a very high value considering that the limit of acceptability
      is 0.70-0.80. The calculation system developed by the Memorial Sloan-Kettering
      Cancer Center provides a predictive value on the histopathologic state of
      sentinel lymph nodes.

PMID- 19579861
TI  - Conformal radiotherapy of clinically localized prostate cancer: analysis of
      rectal and urinary toxicity and correlation with dose-volume parameters.
AB  - AIMS AND BACKGROUND: Rectal and urinary toxicities are the principal limiting
      factors in delivering a high target dose to patients affected by prostate cancer.
      The verification of such toxicity is an important step before starting a dose
      escalation program. The present observational study reports on the acute and late
      rectal and urinary toxicity in relation with dose-volume parameters in 104
      patients with localized prostate cancer treated with 3-dimensional conformal
      radiation therapy. METHODS AND STUDY DESIGN: One hundred and four patients with
      stage T1b-T3b prostate cancer were treated with three-dimensional conformal
      radiation therapy to a total dose of 74 Gy, 2 Gy per fraction. Rigid dose
      constraints were applied for rectum and bladder. Acute and late rectal and
      urinary toxicities were analyzed also in relation to dose-volume histograms.
      Biochemical relapse-free survival was defined according to the American Society
      of Therapeutic Radiation Oncology (ASTRO) criteria and to the RTOG-ASTRO Phoenix
      Consensus Conference Recommendations using the Kaplan-Meier method. RESULTS: No
      grade 3 toxicity was observed. Acute and late grade 2 toxicity rates were 5.8%
      and 9.0% for rectum and 12.5% and 2.0% for bladder, respectively. Rectal V70
      influenced the occurrence of late grade 2 toxicity. A relationship between acute
      and late urinary toxicity was also found. After a median follow-up of 30 months
      (range, 20-50), the actuarial overall and biochemical relapse-free survival rates
      were 84% and 77%, respectively, with a significant difference between low
      intermediate and high-risk patients. CONCLUSIONS: Conformal radiotherapy to the
      dose of 74 Gy was administered with good compliance. The incidence of acute and
      late toxicity was relatively low in accord with our dose constraints. Rectal V70
      proved to be a reliable prognosticator of late toxicity. Overall survival and
      biochemical relapse-free survival rates were more favorable for low and
      intermediate-risk and significantly less favorable for high-risk patients.

PMID- 19579862
TI  - The National Center for Oncological Hadron Therapy: status of the project and
      future clinical use of the facility.
AB  - AIMS AND BACKGROUND: Hadron therapy is an advanced radiotherapy technique that
      employs charged particle beams. Several particles (pions, oxygen, neon and helium
      ions) have been investigated in the past, but at present only protons and carbon
      ions are used in clinical practice. Hadron therapy has been used for more than 50
      years, more than 50,000 patients have been treated worldwide, and many new
      facilities are being built. Indications are still a matter of debate. The Italian
      National Center for Oncological Hadron Therapy (CNAO) is under construction in
      Pavia and will begin to treat patients in the near future. METHODS: The CNAO will
      be a center capable of using both protons and carbon ions. In the first phase,
      three rooms with vertical and horizontal fixed beams will be available,
      subsequently the center will be upgraded with two more rooms equipped with a
      rotating gantry. The facility will use active scanning delivery systems and state
      of-the-art immobilization and setup verification devices. One additional room
      will be devoted to physical and radiobiological research. The CNAO will be a high
      patient-throughput facility capable of treating more than 3,000 patients per
      year. Seven areas of interest have been identified: lung cancer, liver cancer,
      head and neck malignancies, pediatric solid cancers, eye tumors, sarcoma and
      central nervous system cancers. A disease-specific working group has been created
      for each area and has defined selection criteria and protocols to be used at the
      CNAO. Two more working groups are being set up on gynecological and digestive
      (pancreas, biliary tract and rectum) tumors. All the patients will participate in
      clinical trials to establish with sound evidence the real indications for hadron
      therapy. National and international cooperation networks are being set up to
      facilitate patient referral and follow-up. A medical service is already operative
      to assist patients and in selected case to refer them abroad. CONCLUSIONS: The
      CNAO will be the only carbon ion facility in Italy and will have an international
      basin. Close cooperation with existing oncological centers is of paramount
      importance to fully exploit its potential.

PMID- 19579863
TI  - Changes in glucose metabolism during and after radiotherapy in non-small cell
      lung cancer.
AB  - AIMS AND BACKGROUND: Evaluation of the metabolic response to radiotherapy in
      nonsmall cell lung cancer patients is commonly performed about three months after
      the end of radiotherapy. The aim of the present study was to assess with positron
      emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose
      changes in glucose metabolism during and after radiotherapy in non-small cell
      lung cancer patients. METHODS AND STUDY DESIGN: In 6 patients, PET/CT scans with
      [18F]fluorodeoxyglucose were performed before (PET0), during (PET1; at a median
      of 14 days before the end of radiotherapy) and after the end of radiotherapy
      (PET2 and PET3, at a median of 28 and 93 days, respectively). The metabolic
      response was scored according to visual and semiquantitative criteria. RESULTS:
      Standardize maximum uptake at PET1 (7.9 +/- 4.8), PET2 (5.1 +/- 4.1) and PET3
      (2.7 +/- 3.1) were all significantly (P < 0.05; ANOVA repeated measures) lower
      than at PET0 (16.1 +/- 10.1). Standardized maximum uptake at PET1 was
      significantly higher than at both PET2 and PET3. There were no significant
      differences in SUV(max) between PET2 and PET3. PET3 identified 4 complete and 2
      partial metabolic responses, whereas PET1 identified 6 partial metabolic
      responses. Radiotherapy-induced increased [l8F]fluorodeoxyglucose uptake could be
      visually distinguished from tumor uptake based on PET/CT integration and was less
      frequent at PET1 (n = 2) than at PET3 (n = 6). CONCLUSION: In non-small cell lung
      cancer, radiotherapy induces a progressive decrease in glucose metabolism that is
      greater 3 months after the end of treatment but can be detected during the
      treatment itself. Glucose avid, radiotherapy-induced inflammation is more evident
      after the end of radiotherapy than during radiotherapy and does not preclude the
      interpretation of [18F]fluorodeoxyglucose images, particularly when using PET/CT.

PMID- 19579864
TI  - Squamous cell carcinoma metastatic to cervical lymph nodes from an unknown
      primary site: the impact of radiotherapy.
AB  - AIMS AND BACKGROUND: Cervical lymph node metastases of squamous cell carcinoma
      from an unknown primary site constitute about 5% of the total head and neck
      cancer, cases. The management of these patients is still a therapeutic challenge.
      The aim of the present study was to analyze the prognosis in a series of patients
      and, in particular, the impact of different radiotherapy techniques on the
      prognosis. METHODS AND STUDY DESIGN: Data from 60 patients with cervical lymph
      node metastases of squamous cell carcinoma from an unknown primary site were
      reviewed. Nine of 60 patients (15.0%) received excisional biopsy. Radiotherapy
      was delivered to the bilateral neck and pharyngeal mucosa (extensive field) in 11
      patients (18.3%), to the bilateral neck in 24 patients (40.0%), and to the
      ipsilateral neck in 25 patients (41.7%). Fourteen patients (23.3%) also received
      chemotherapy. RESULTS: The 5-year overall survival rate of all patients was
      68.5%. The overall survival of patients with N1, N2, and N3 stage was 100%,
      68.0%, and 40.9%, respectively (P = 0.026). The overall survival of patients
      irradiated by ipsilateral neck, bilateral neck, and extensive field was 66.5%,
      74.5%, and 54.6%, respectively (P = 0.5). At multivariate analysis, only N stage
      significantly affected overall survival (P = 0.032). The 5-year neck control rate
      of all patients was 65.6%. The neck control rate of patients with N1, N2, and N3
      stage was 100%, 63.2%, and 34.6%, respectively (P = 0.064). The neck control rate
      of patients irradiated by ipsilateral neck, bilateral neck, and extensive field
      was 87.6%, 51.1%, and 72.7%, respectively (P = 0.279). Emergence of the occult
      primary was observed in 21.2% patients, and all of these occurred within the head
      and neck region. The primary tumor emerged in 23.3% of patients treated with
      ipsilateral and bilateral neck irradiation and in 12.5% of patients irradiated by
      extensive field (P = 0.469). CONCLUSIONS: Patients with cervical lymph node
      metastases of squamous cell carcinoma from an unknown primary site have clinical
      features and a prognosis similar to those of other head and neck malignancies.
      Extensive irradiation results in a lower trend of emergence of the primary tumor
      than when patients are treated with ipsilateral and bilateral irradiation, but
      there is no significant difference in overall survival.

PMID- 19579865
TI  - Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus
      concomitant and adjuvant temozolomide: a long-term analysis.
AB  - AIMS AND BACKGROUND: Glioblastoma is the most common primary brain tumor in
      adults. The standard treatment is surgery and radiotherapy. In this study, the
      results of radiotherapy plus concomitant and adjuvant temozolomide are reported.
      In addition, the efficiency of adjuvant temozolomide is evaluated. METHODS AND
      STUDY DESIGN: Forty-one patients were analyzed. All patients received
      radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and
      concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after
      surgery. Thirty-one patients received an average of 6 cycles (range, 1-8 cycles)
      of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose
      of 200 mg/m2/day. The primary end point was overall survival. RESULTS: The median
      overall survival was 16.7 months. The overall survival significantly increased in
      the adjuvant temozolomide group compared to the group with no adjuvant therapy
      (18.9 vs 9.8 months). The difference in overall survival between adjuvant
      temozolomide cycles of < or = and > 3 was significant (8.7 vs 20 months). On
      multivariate analyses, the important prognostic factors were type of surgery and
      application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity
      was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy,
      respectively. CONCLUSIONS: The study confirmed the effectiveness of radiotherapy
      plus temozolomide in newly diagnosed glioblastoma. It was established that the
      application of adjuvant temozolomide for at least 4 cycles is required to obtain
      a benefit from adjuvant therapy. However, further studies are needed to confirm
      these data.

PMID- 19579866
TI  - Radiotherapy after partial laryngectomy: an analysis of 36 cases and a proposal
      to optimize radiotherapy.
AB  - AIMS AND BACKGROUND: Laryngeal cancer treatment options include radical surgery,
      "organ preservation surgery", radiotherapy and chemotherapy. There is no proven
      evidence of a significant increase in late toxicity with adjuvant radiotherapy
      after conservative surgery. The aim of this retrospective study was to evaluate
      the toxicity, local-regional control and overall survival of adjuvant
      radiotherapy after conservative surgery. METHODS: A total of 36 patients was
      treated with radiotherapy after partial laryngectomy at the Radiotherapy
      Department of the Institute for Cancer Treatment and Research (IRCC) of Candiolo
      and of the Mauriziano Hospital in Turin, between 1994 and 2007. The postoperative
      treatment doses ranged from 45 to 70.2 Gy with conventional fractionation. The
      Kaplan-Meier method was applied for statistical analysis. The RTOG-EORTC scale
      was used to evaluate late and acute toxicity. RESULTS: Overall 5- and 10-year
      survival was 93% and 47%, respectively. Local control was 93.5% at 5 and was
      unchanged at 10 years. Grade 2 acute cutaneous and mucous toxicity was 41% and
      62%, and grade 3, 6.9% and 3.5%, respectively. Only one patient required
      percutaneous endoscopic gastrostomy due to severe dysphagia and one patient
      required temporary tracheostomy for severe acute laryngeal edema (grade 3). Two
      patients experienced late toxicity greater than grade 3. The median dose to the
      residual larynx was 59.5 Gy (range, 45-70.2), and the median dose to the neck was
      50.4 Gy (range, 39.6 -55.8). CONCLUSIONS: The results of our study showed a dose
      dependent increase in the late toxicity trend at doses over and above 60 Gy,
      which is higher than the cutoff dose reported in the literature. There was no
      indication from our data that adjuvant postoperative radiotherapy means
      additional toxicity. The use of highly conformal techniques can further reduce
      toxicity of the radiotherapy.

PMID- 19579867
TI  - Factors related to recurrence after pathological complete response to
      postoperative chemotherapy in patients with epithelial ovarian cancer.
AB  - AIMS AND BACKGROUND: It has been appreciated for some time that the lack of
      detection of ovarian cancer at clinical and pathological (second-look laparotomy)
      evaluation is not synonymous with cure. The goal of this study was to define
      clinical risk factors for recurrence after complete pathological response to
      postoperative chemotherapy in patients with epithelial ovarian cancer. METHODS:
      Fifty-seven patients who met the inclusion criteria of our study were evaluated.
      The characteristics (age, menopausal status, histological subtype, tumor grade,
      presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual
      tumor volume after primary surgery) of patients with and those without tumor
      recurrence were compared. RESULTS: The median follow-up was 52 months (range, 15
      142 months). The overall survival rates of the patients were 100%, 96%, and 87%
      at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57
      (37%) patients had recurrent disease. The median time to recurrence was 16
      months. Recurrences were most frequent in the pelvis and abdominal cavity (38%).
      Age, menopausal status, stage at diagnosis, and residual tumor volume after
      initial surgery were significantly related to the risk of recurrence in
      univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual
      tumor volume after initial surgery was found to be the only significant
      independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99).
      CONCLUSION: We believe it is necessary to conduct randomized studies on this
      issue because insight into predictors of recurrence after pathological complete
      response to postoperative chemotherapy could be used to select patients for
      trials of consolidation therapy.

PMID- 19579868
TI  - Psychosexual and body image aspects of quality of life in Turkish breast cancer
      patients: a comparison of breast conserving treatment and mastectomy.
AB  - AIMS AND BACKGROUND: Assessing psychosexual and body image aspects of quality of
      life in Turkish breast cancer patients treated by either mastectomy or breast
      conserving treatment (BCT). METHODS: The study group consisted of 112 patients
      who had undergone all treatment at a single institution under the care of a
      multidisciplinary breast team. Following surgery, all patients underwent adjuvant
      radiotherapy with or without chemotherapy and hormone therapy. At the time of
      this study all patients were disease free with at least 2 years' follow-up.
      Twenty percent of the patients were premenopausal and 80% postmenopausal. The
      patients completed a questionnaire consisting of 42 questions related to their
      sexual relations and body image. RESULTS: Forty-one percent of sexually active
      patients had experienced a deterioration of sexual functioning after treatment.
      This was mainly due to loss of libido (80%), loss of interest in partner (54%),
      and sexual dissatisfaction (59%). Problems tended to develop early in the course
      of treatment. Decreased sexual desire was significantly more frequent in patients
      undergoing mastectomy versus BCT (80% vs 61%; P = 0.043) and in premenopausal
      versus postmenopausal patients (P = 0.024). Although 80% of patients were
      satisfied with their appearance as a whole, only 54% liked their naked bodies.
      There was no significant difference in body image scores between patients
      undergoing mastectomy or BCT apart from a general feeling of physical
      unattractiveness in mastectomy patients (3.4 vs 2.8; P = 0.03). CONCLUSIONS:
      Significant, similar psychosexual and body image problems occur in patients
      treated for breast cancer with either mastectomy or BCT. Problems arise early in
      the course of the disease and therefore detection and treatment of these problems
      should be addressed during the patients' initial assessment and at the start of
      treatment. These findings are similar to those reported on similar groups of
      treated women in American and European populations.

PMID- 19579869
TI  - Cost-effectiveness of pegfilgrastim versus six days of filgrastim for preventing
      febrile neutropenia in breast cancer patients.
AB  - AIMS AND BACKGROUND: Febrile neutropenia (FN) is a major complication of
      chemotherapy and is associated with substantial morbidity, mortality and costs.
      The aim of this study was to evaluate the cost-effectiveness of primary
      prophylaxis with, pegfilgrastim versus six-day filgrastim in preventing FN in
      Italian patients with early-stage breast cancer receiving adjuvant chemotherapy
      associated with a > or = 20% FN risk. METHODS: The pharmacoeconomic evaluation
      was based on a decision-analytic model taking into account the possible
      consequences of FN (e.g., death and reduction/delay of chemotherapy dose).
      Parameters included in the model were relative risk of FN with pegfilgrastim
      versus six-day filgrastim; direct costs (drug purchase and FN-related
      hospitalizations); relative risk of relative dose intensity < 85% with
      pegfilgrastim versus filgrastim; impact on long-term survival due to relative
      dose intensity < 85%; and impact of age on FN and relative dose intensity < 85%.
      RESULTS: Under base-case assumptions, pegfilgrastim was cost-effective compared
      to six-day filgrastim in Italy. The estimated cost, life expectancy and quality
      adjusted life years per person for pegfilgrastim were Euro 3078, 16.47 years, and
      15.32; the corresponding figures for six-day filgrastim were Euro 3033, 16.35
      years, and 15.22. The corresponding incremental cost-effectiveness ratio with
      pegfilgrastim was Euro 409 per life-year gained and Euro 429 per quality-adjusted
      life year gained. One-way sensitivity analyses showed that the results were most
      sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim.
      The results were moderately sensitive to the cost of pegfilgrastim and
      filgrastim, cost of drug administration, cost of FN hospitalization, and number
      of chemotherapy cycles. Pegfilgrastim remained cost-effective, with an
      incremental cost-effectiveness ratio well below the accepted limit of Euro 50,000
      per life year gained in all one-way sensitivity analyses. A two-way sensitivity
      analysis on cost of drugs showed a range of pegfilgrastim dominance over six-day
      filgrastim. CONCLUSIONS: At the current official price in Italy, primary
      prophylaxis with pegfilgrastim improved health outcomes with a very limited cost
      increase for the National Health Service payer. Even when very low prices of
      filgrastim and high prices of pegfilgrastim were considered in the model, the
      resulting incremental cost-effectiveness ratio remained well within the
      acceptable cost-effectiveness limit of Euro 50,000/quality-adjusted life year.

PMID- 19579870
TI  - Increased transglutaminase 2 and GLUT-1 expression in breast tumors not
      susceptible to chemoprevention with antioxidants.
AB  - GOALS: Expression of GLUT-1 and transglutaminase 2 is increased in aggressive
      breast cancer, whereas claudin-1, which is expressed in normal tissues, is absent
      in such tumors. This experimental study was undertaken to establish the
      aggressiveness and prognosis of DMBA-induced mammary tumors in female Wistar rats
      based on the assessment of these markers. MATERIALS AND METHODS: The rats were
      divided into two groups, a control group (n = 70) and a chemoprevention group (n
      = 70). Breast tumors were induced in both groups by administration of 7,12
      dimethylbenz[a] anthracene (DMBA). The chemoprevention group also received alpha
      tocopherol and a solution of micronutrients containing ascorbic acid and
      selenium. Neoplastic lesions of both groups were randomly selected for
      immunohistochemical assessment of the expression of GLUT-1, transglutaminase 2
      and claudin-1. RESULTS: A higher proportion of mammary tumors expressed GLUT-1
      and transglutaminase 2 in the chemoprevention group. Claudin-1 expression was
      absent in all tumors of both groups. CONCLUSIONS: These results are suggestive of
      increased aggressiveness of tumors not susceptible to chemoprevention by the
      agents used in this study.

PMID- 19579871
TI  - Spontaneous rupture of giant gastric GIST presenting as hemoperitoneum and
      mimicking cavernous liver angioma.
AB  - Spontaneous rupture of gastrointestinal stromal tumor (GIST) with hemoperitoneum
      is an extremely rare clinical presentation of this mesenchymal tumor. We report
      the unusual case of a 68-year-old man who was admitted to the hospital with
      abdominal pain. While waiting for the results of his laboratory tests the patient
      became pale and tachycardic and his abdomen distended with generalized rebound
      tenderness. A CT scan suggested rupture of a cavernous angioma of the liver and
      the patient was brought to the operating room for an explorative laparoscopy,
      which revealed hemoperitoneum from a ruptured giant gastric GIST. After
      conversion to laparotomy, the tumor was excised: it was 11 x 10 x 5 cm in size,
      with massive necrosis and clotted blood inside. Immunohistochemical examination
      revealed reactivity to c-KIT and CD34, consistent with the diagnostic criteria
      for GIST, with low mitotic activity (< 5/50 HPF). The postoperative course was
      uneventful, and the clinical and radiological follow-up at 6 months is negative
      for recurrence.

PMID- 19579872
TI  - Molecularly targeted therapy and radiotherapy in the management of localized
      gastrointestinal stromal tumor (GIST) of the rectum: a case report.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract. The main treatment for localized gastrointestinal
      stromal tumors is surgical resection. These tumors respond poorly to conventional
      cytotoxic chemotherapy agents and to radiotherapy. Imatinib mesylate, a small
      molecule kinase inhibitor, has proved useful in the treatment of recurrent or
      metastatic GISTs and is now being tested in the adjuvant and neoadjuvant setting.
      The role of radiotherapy in the management of patients with GIST is currently
      restricted to symptomatic palliation. We present the case of a 54-year-old man
      affected by rectal GIST extending to the anal canal, with constipation,
      hematochezia, and anal pain. He received imatinib, 400 mg orally per day, for a
      week before and during radiation therapy. Irradiation was delivered to the gross
      tumor volume by 3D conformal therapy. The planned total dose was 50.4 Gy in
      fractions of 1.8 Gy daily. We observed a partial clinical response 3 weeks after
      the end of combination treatment. The patient then underwent a sphincter-saving
      surgical procedure. There was no perioperative morbidity and a complete
      pathological response was obtained. At the present time, the role of radiotherapy
      in the management of patients with GIST is restricted to symptomatic palliation.
      The introduction of molecularly targeted therapy combined with radiation therapy
      could improve the outcomes for patients diagnosed with GIST.

PMID- 19579873
TI  - Association of gastrointestinal stromal tumor and acute myeloid leukemia preceded
      by myelodysplastic syndrome with refractory anemia.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. GISTs are believed to be related to mutational
      activation of receptor tyrosine kinases, KIT, or platelet-derived growth factor
      receptor-alpha. The coexistence of GISTs with other neoplasms has been
      extensively addressed in the literature. The most common second neoplasms are
      colorectal cancer, prostate cancer, and neoplasms derived from lymphoid tissue.
      In this case report, we describe a patient affected by GIST and acute myeloid
      leukemia preceded by myelodysplastic syndrome with refractory anemia. The
      clinicopathological characteristics of the patient are discussed and the
      literature is reviewed.

PMID- 19579874
TI  - Thymoma associated with myasthenia and autonomic anti-Hu paraneoplastic
      neuropathy.
AB  - Along with myasthenia, other paraneoplastic neurological syndromes (PNS) may
      occur in thymoma. Anti-Hu antibodies and a clinical "anti-Hu syndrome"
      characterized by encephalitis and/or painful neuropathies have been reported in
      only three patients at the time of the diagnosis of thymoma. We describe a severe
      anti-Hu-related autonomic neuropathy with gastrointestinal paresis and intestinal
      pseudo-obstruction with malabsorption that occurred concomitantly with the
      worsening of myasthenic symptoms long after the initial diagnosis of thymoma in a
      young patient. The clinical anti-Hu syndrome preceded the radiological diagnosis
      of thymoma recurrence. Treatment with plasma exchange led to a transient
      improvement of neurological symptoms.

PMID- 19579875
TI  - An unusual cause of a parotid mass in an immunocompetent host: classic Kaposi's
      sarcoma.
AB  - Kaposi's sarcoma (KS) is a virally driven vascular tumor that usually has a
      multifocal origin, with multiple vascular nodules in the skin and other organs,
      particularly the gastrointestinal tract. Four variants of KS have been described:
      HIV-related, African, iatrogenic and classic. Primary classic KS of the head and
      neck is rare in any case, but KS arising in intraparotid lymph nodes, especially
      with no cutaneous involvement, is exceptionally rare. We report the case of an
      immunocompetent 71-year-old man who presented with a three-month history of a
      slowly progressive swelling in the right parotid region. After parotidectomy and
      histopathological diagnosis of lymph node localization of KS, a thorough
      dermatological examination did not reveal any skin lesions, and chest and
      abdominal computed tomography scans, esophagogastroduodenoscopy, and fecal occult
      blood test were all negative for visceral and other lymph node localizations. We
      here discuss the peculiarity of the presentation, the differential diagnosis, and
      the management strategy of such a rare disease.

PMID- 19579876
TI  - Bone metastases from primary cardiac sarcoma: case report.
AB  - Tumor spread from primary cardiac sarcoma to the bone is very rare and has a poor
      prognosis. Only six cases have been reported in the literature. We present a 32
      year-old female patient with bone metastases from primary cardiac sarcoma.

PMID- 19579877
TI  - Supraclavicular metastases from a sex cord stromal tumor of the ovary.
AB  - Metastases to the supraclavicular fossa usually originate from head and neck or
      infraclavicular tumors. Ovarian primaries of supraclavicular metastases are very
      rare. Sex cord stromal tumors of the ovary account for 5-8% of all ovarian
      malignancies and there have been only a few case reports on distant metastases
      from these tumors. A 46-year-old woman presented to us with a left
      supraclavicular mass. She had had a sex cord stromal tumor in the right ovary
      four years before. Comprehensive clinical investigation and fine-needle
      aspiration cytology were performed. The lesion had the characteristics of a sex
      cord stromal tumor. To our knowledge, this is the first report of such a case in
      the English literature. We discuss its pathological and clinical features in the
      light of the current knowledge.

PMID- 19579878
TI  - Spontaneous regression of two giant basal cell carcinomas in a single patient
      after incomplete excision.
AB  - BACKGROUND: Spontaneous regression of small basal cell carcinoma has been
      reported. For giant basal cell carcinoma, however, no spontaneous regression has
      been described to date. CASE REPORT: We present a patient with two independent
      giant basal cell carcinomas over the left clavicle and the lower back, measuring
      7 x 12 cm and 18 x 20 cm, respectively. Both tumors were excised incompletely
      (R2) and the patient refused followup resections. After 52 and 16 months,
      respectively, no signs of recurrence were observed. CONCLUSION; Incompletely
      excised giant basal cell carcinomas can regress spontaneously. A watch-and-wait
      approach after incomplete resection may be pragmatic to avoid mutilating follow
      up resections in patients refusing further surgery.

PMID- 19579879
TI  - Low-grade fibromatosis-like spindle cell metaplastic carcinoma: a basal-like
      tumor with a favorable clinical outcome. Report of two cases.
AB  - Fibromatosis-like spindle-cell metaplastic carcinoma (FLSpCC) is an atypical
      variant of spindle-cell carcinoma with a particular clinical behavior
      characterized by frequent local recurrence, very low potential for axillary lymph
      node metastasis, and uncommon distant metastases. Although it presents the
      typical immunoprofile of basal-like carcinomas, FLSpCC is associated with a
      favorable clinical outcome and conservative treatment is generally indicated.
      Because of the lack of specific clinical and radiological characteristics, the
      criteria for the differential diagnosis from other benign and malignant tumors
      are based only on histological findings and immunostaining. We report on two
      FLSpCC patients treated with wide local excision and mastectomy associated with
      axillary lymph node dissection. Although the biological behavior of this subtype
      of breast cancer has not been adequately evaluated, wide local excision or
      mastectomy with clear resection margins but no axillary dissection appears to be
      an adequate treatment approach.

PMID- 19579880
TI  - If subclinical turns into suboptimal.

PMID- 19579881
TI  - Radiochemotherapy with cisplatin and oral tegafur in advanced head and neck
      cancer: long-term results of a phase II study.

PMID- 19579882
TI  - [Review of current treatment for hot flushes induced by androgen deprivation in
      prostate carcinoma].
AB  - Considering the currently increased incidence, prevalence and survival of
      prostate cancer, the management of hot flushes associated with LH-RH analog
      treatment must be taken into account. The most widely used and effective
      treatment is hormone replacement, though the latter is not without risks. It is
      presently possible to address hot flushes in these patients based on a broad
      range of treatment options in which hormone therapy may constitute a last option,
      due to the risk of tumor relapse or progression -- since prostate cancer is
      hormone sensitive. The present study reviews the currently used treatments and
      hygiene-dietary measures that may help reduce the symptoms. A review is made of
      both hormone and non-hormone therapies, based on the existing scientific
      evidence. Drugs such as the new antidepressants, gabapentin and clonidine may
      play an important role in the management of hot flushes. While the underlying
      mechanisms of action are varied, they are related to the complex feedback exerted
      by the sexual hormones upon the hypothalamic secretion of noradrenalin -- this
      being the principal etiological factor of hot flushes.

PMID- 19579883
TI  - [Prostate cancer: evidence based clinical practice].
AB  - OBJECTIVES: Evidence-based medicine allows the best available external clinical
      evidence from systematic literature research to be graded in order to determine
      the strength of its recommendation. This guideline aims to assist physicians and
      health professionals in clinical decisions related to prostate cancer treatment,
      particularly in urology, clinical oncology and radiotherapy. METHODS: The
      publications used as information sources were obtained from structured data
      search in electronic databases, such as CENTRAL (Cochrane Central Register of
      Controlled Clinical Trials) and MEDLINE (online). Each item of this guideline
      derived from an original question which was distributed to the participants.
      Search strategies were prepared to select the studies presenting the best
      methodological quality, according to predefined levels of evidence. RESULTS: All
      the recommendations were followed by a level of evidence (LE) and a degree of
      recommendation (DR). We used a formal ranking system to help the reader to judge
      the strength of the evidence behind the results published in support of each
      recommendation. CONCLUSIONS: The existing parameters should be viewed as
      guidelines of conduct. The final trial on which the clinical procedure or
      treatment plan is most suitable for a particular patient should be done by a
      physician, who should discuss the available treatment options with the patient
      according to the diagnosis.

PMID- 19579884
TI  - [The impact of statins use in clinically localized prostate cancer treated with
      radical prostatectomy].
AB  - INTRODUCTION: Use of statins has been associated with reduced risk, progression
      and mortality of some tumors, including prostate cancer (CaP). According to
      recent Studies, long-term treatment with statins significantly reduces the risk
      of PC and also confers a protective effect against advanced or aggressive CaP.
      However, there is no conclusive data regarding the potential effect on patients
      diagnosed with clinically localized CaP undergoing radical treatment. MATERIALS
      AND METHODS: A retrospective study was performed in a cohort of 250 patients that
      did not undergo screening and diagnosis in clinical practice of localized CaP
      (T1c-T2cNxM0). All patients were treated with radical prostatectomy between 2001
      and 2008. Data about clinical and pathological findings, and also the existence
      of dyslipemia as well as treatment with statins for at least 5 years was
      collected and analyzed. A logistic regression analysis was performed to determine
      the independent predictive variables related with a more favorable pathology.
      RESULTS: In our study, we found a relationship, using a univariate analysis,
      between treatment with statins and the presence of insignificant carcinoma in the
      group with low or intermediate risk of recurrence. However, this relationship is
      not independent when we applied a multivariate analysis. DISCUSSION: Hypothesis
      about the potential effect of the statins preventing or inhibiting the
      development of high risk CaP needs to be proven applying specific clinical trials
      designed for this purpose. There isn't conclusive data that demonstrate that
      statins lower the risk of development of potentially lethal high grade CaP.

PMID- 19579885
TI  - [Retrospective evaluation of urinary continence in patients submitted to
      brachytherapy after transurethral resection of the prostate gland].
AB  - INTRODUCTION AND OBJECTIVE: Some candidates for brachytherapy present with a
      previous history of prostate transurethral resection (TURP). Nonetheless, TURP
      generates a cavity that may lead to technical difficulties in performing
      brachytherapy. Such condition make a history of previous TURP a relative contra
      indication for brachytherapy. The aim of this study is to evaluate the role of
      brachytherapy in urinary continence, in a group of patients with previous history
      of TURP. MATERIALS AND METHODS: In our study, we analysed a group of 16 patients
      submitted to TURP pre-brachytherapy. The mean quality of life score from
      ICSmaleSF questionnaire ranged from 0 to 1 before and after brachytheraphy
      (average: 0,18 -- before; average: 0,20 -- after). There was no estatistically
      significant difference between the former values (p<0,001). After brachytherapy
      patients were evaluated for lower urinary tract symptoms. The time interval
      between TURP and brachytherapy ranged from 30 to 90 days (average: 60 days). Post
      brachytherapy follow-up varied between 3 and 60 months (average: 30 months).
      RESULTS: None of the 16 patients evaluated presented lower urinary tract symptoms
      nor urinary incontinence. Medical complications observed in patients were:
      dysuria, erectile dysfunction, scrotal ecchymosis and urinary retention. The
      cases of dysuria, scrotal ecchymosis and urinary retention observed were of short
      duration, the last one with spontaneous resolution after 7 days of vesical
      catheterism. The patient presenting erectile dysfunction had a good response to
      oral type 5 fosfodiesterase inhibitor three times a week, after a six month
      period. CONCLUSION: In accordance with other studies, we believe that with some
      strategy TURP should not be considered a relative contra-indication for
      brachytherapy.

PMID- 19579886
TI  - [EAU guidelines on non-muscle-carcinoma of the bladder].
AB  - CONTEXT AND OBJECTIVE: To present the updated version of 2008 European
      Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer.
      EVIDENCE ACQUISITION: A systematic review of the recent literature on the
      diagnosis and treatment of non-muscle-invasive bladder cancer was performed. The
      guidelines were updated and the level of evidence and grade of recommendation
      were assigned. EVIDENCE SYNTHESIS: The diagnosis of bladder cancer depends on
      cystoscopy and histologic evaluation of the resected tissue. A complete and
      correct transurethral resection (TUR) is essential for the prognosis of the
      patient. When the initial resection is incomplete or when a high-grade or T1
      tumour is detected, a second TUR within 2-6 wk should be performed. The short-
      and long-term risks of both recurrence and progression may be estimated for
      individual patients using the scoring system and risk tables. The stratification
      of patients to low, intermediate, and high-risk groups-separately for recurrence
      and progression-represents the cornerstone for indication of adjuvant treatment.
      In patients at low risk of tumour recurrence and progression, one immediate
      instillation of chemotherapy is strongly recommended. In those at an intermediate
      or high risk of recurrence and an intermediate risk of progression, one immediate
      instillation of chemotherapy should be followed by further instillations of
      chemotherapy or a minimum of 1 yr of bacillus Calmette-Guerin (BCG). In patients
      at high risk of tumour progression, after an immediate instillation of
      chemotherapy, intravesical BCG for at least 1 yr is indicated. Immediate
      cystectomy may be offered to the highest risk patients and in patients with BCG
      failure. The long version of the guidelines is available on www.uroweb.org.
      CONCLUSIONS: These EAU guidelines present the updated information about the
      diagnosis and treatment of non-muscle-invasive bladder cancer and offer the
      recent findings for the routine clinical application.

PMID- 19579887
TI  - [Renal tumor with inferior vena cava thrombus. Surgical approach and prognosis].
AB  - OBJECTIVES: The aim of this study was to evaluate strategies used for surgical
      management of renal cell carcinoma with tumoral thrombus extension in the
      inferior vena cava (IVC) and evaluate patient's prognosis. METHODS: [corrected]
      Fifteen patients with renal tumor and IVC thrombus, underwent radical nephrectomy
      and thrombectomy, and were retrospectively evaluated. Patients were followed for
      0 to 36 months (mean of 9.5 months). Computed tomography (CT) scan with three
      dimensional reconstruction was used to define IVC thrombus level. RESULTS: The
      mean age was 54 years, range from 16 to 79. The thrombus was classified as level
      I -- 13.5%, level II -- 40%, level III -- 26.5% and level IV -- 20%. Surgery was
      performed with cardiopulmonary bypass (CPB) in six (40%) cases, three (50%)
      without sternotomy. There was one (13%) death during the intraoperative period;
      this patient presented extensive metastatic tumor, with the thrombus reaching the
      right atrium. Patients with lymph node or metastatic disease at initial
      presentation had poorer overall survival in Kaplan-Meier curve. Both, tumor stage
      (p = 0.380), and thrombus extension (p = 0.174) were not related to survival.
      CONCLUSIONS: Despite its morbidity and mortality, radical nephrectomy with
      thrombectomy should be performed in case of renal cell carcinoma with tumoral
      thrombus, because it can offers the possibility of local control. Patients with
      lymph node and distant metastatic disease have poor prognoses.

PMID- 19579888
TI  - [Cavernous tissue rehabilitation whit sildenafil 100 mg in patients after radical
      prostatectomy].
AB  - OBJECTIVES: We try to figure out whether early penile rahabilitation ameliorates
      erectile dysfunction secondary to radical prostatectomy. MATERIAL AND METHODS:
      Retrospective study of 80 cases of patients that were operated between 2005-2008;
      all of them went under radical prostatectomy and were treated with sildenafil 100
      mg every second day (Monday, Wednesday and Friday) plus 100 mg on demand after
      the surgery. As objective measurements, we used validated questionnaire IIEF-5
      and also axil penile rigidity before and after surgery in the third and ninth
      month. RESULTS: Patients treated with sildenafil in fixed doses presented a 60%
      full erection recovery 9 months after radical prostatectomy. In the case where
      patients underwent bilateral or unilateral nerve sparing, they got a successful
      rate of almost 90%. Even 20% of those patients who did not have a nerve
      preservation got satisfactory erections, CONCLUSIONS: Our experience shows that
      early penile rehabilitation seems to be a good treatment for erectile dysfunction
      after radical prostatectomy with IPDE5 in fixed doses. Administration every other
      day plus on demand looks like also as an appropriate option.

PMID- 19579889
TI  - [Cystic displasia of the testis. Review of literature].
AB  - OBJECTIVE: Review this pathology nowadays. METHODS: We search in Medline/PubMed
      database for reviews about cystic dysplasia of the testis. We review and discuss
      the relevant literature about it. RESULTS: Cystic dysplasia of the testis (CDT)
      is a rare benign disease, associated with upper urinary tract malformations. Its
      most frequent clinical manifestation is the increase of testicular size; the
      presence of cysts is demonstrated by ultrasound. No consensus exists in its
      treatment, it oftenly requires histological confirmation, performing testicle
      sparing surgery. CONCLUSION: CDT needs to be taken into account in the
      differential diagnosis of childhood testicular tumors.

PMID- 19579891
TI  - [Transcoccigeal colpopexy with polyprolylene mesh with helper orifices for the
      treatment of posterior vaginal wall prolapse: anatomical and functional results].
AB  - OBJECTIVE: The creation of neo utero-sacral neoligaments, decribed by Petros,
      evolved into a new procedure allowing for the anatomical reconstruction of the
      three levels proposed by DeLancey. The aim of this study is evaluate the
      anatomical and functional outcomes of this minimally invasive procedure. PATIENTS
      AND METHOD: From December 2004 to March 2007, a total of 34 patients with
      posterior defect grade III or higher underwent this procedure. The minimum follow
      up was 13 months Mean age was 63 years. The site of fixation was the Sacrospinous
      ligament. SURGICAL TECHNIQUE: The ischiorectal fossa is dissected. Next two small
      skin incisions are made 3 cm lateral and inferior to the center of the anus. A
      proper needle is introduced, vertically towards the sacrospinal ligament at the
      level of the ischial spine, guided by the surgeon index finger, 2 cm medially
      avoiding the Alcok canal. The armpit of the mesh is connected to the tip of the
      needle and brought to the perineal region. No site specific correction is made.
      RESULTS: The cure rate was 94,7% and recurrence rate was 5,3%. No visceral,
      nerurovascular injuries were observed. The mesh exposure rate (less than 1 cm2)
      was (14.7%) and all patients were treated conservatively with no impact on the
      outcome. There were transient dyspareunia in 2 (11.8%) of the 17 sexually active
      patient and persistent in 1 case (5.9%). CONCLUSIONS: This procedure is an
      attractive minimally invasive alternative for the anatomical and functional
      reconstruction of the posterior and apical defects.

PMID- 19579890
TI  - [Dehydroepiandrosterone (DHEA), review of its efficiency in the managing of the
      libido decrease and other symtoms of aging].
AB  - INTRODUCTION: The DHEA widely used for the control of the symptoms associated
      with the aging, has been an object of numerous clinical essays with discordant
      results as for its efficiency. OBJECTIVES: The present review tries to analyze
      the existing information by means of a search and systematic review of articles
      centred on the utilization of the DHEA/S for the control of the aging symptoms.
      MATERIAL AND METHODS: Systematic review of the literature and application of the
      skills of metaanalisis to value the efficiency of the DHEA/S, for it settles down
      the process of prospective form, 152 articles were checked and 25 were in use for
      adding only their results. RESULTS: Since the only (unique) prominent information
      seems to concern the metabolism of the carbohydrates increasing the efficiency of
      the insulin. CONCLUSIONS: The studies do not sustain the usefulness of the DHEA
      for the reduction of the symptoms associated with the aging.

PMID- 19579892
TI  - [Assessment of the health-related quality of life impact in female with mixed
      urinary incontinence].
AB  - BACKGROUND: Health-related quality of life (HRQoL) assessment on female with
      urinary incontinence (UI) may be a useful indicator in the management of early
      treatment depending on the sort of UI which is dominant: Stress UI or Urge UI.
      The objective of the present study was to evaluate the HRQoL of female with mixed
      UI, comparing the impact of symptoms of Urge UI and Stress UI. PATIENTS AND
      METHODS: This is an epidemiologic, cross-sectional and multicenter study. HRQoL
      of 1,100 women with mixed UI was evaluated using the Spanish version of "King's
      Health Questionnaire" (KHQ). Personal data of patients were also collected along
      with medical records and clinical data related to diagnostic and treatment of UI.
      RESULTS: Urinary infection was the most frequent medical record found. Mean time
      since start of UI symptoms was 4 years and 44% of patients had been received some
      treatment for UI. It was observed a higher use of sanitary napkins (63.9%) than
      pantyliners (36%) and diapers (11.2%). Mean global score of the KHQ was 42.2
      (S.D.= 18.7); higher impact on HRQoL was shown in dimensions: UI impact, Urinary
      problems and Physical Limitations. Urge UI symptoms cause higher impact on HRQoL
      than Stress UI symptoms (p< 0.0001). The logistic regression model performed for
      global KHQ score showed that variables strongly associated were Urge UI, genital
      prolapse and coital UI symptom. CONCLUSIONS: Women with mixed UI showed and
      important impact on HRQoL. This impact is strongly associated with presence of
      symptoms of Urge UI.

PMID- 19579893
TI  - [Surgical approach of traumatic urethral injury in children. Experience at San
      Vicente of Paul Universitary Hospital. Medellin 1987-2007].
AB  - OBJECTIVE: In order to evaluate the efficacy of different surgical techniques for
      the correction of traumatic lesions of the urethra, we performed a retrospective
      study in those patients, and evaluated different complications such as
      postsurgical stenosis of the urethra, incontinence and impotence (erectile
      dysfunction). METHODS: A retrospective study was conducted, reviewing the
      clinical charts of 43 patients admitted to the San Vicente of Paul Hospital, with
      diagnosis of traumatic rupture of the posterior urethra from 1987 to 2007. We
      analyzed different demographic data, type of surgical correction, early and late
      complications. RESULTS: The average age of the patients was 7.7 years, the
      average follow up was 30.6 months, and all the patients were male with a
      posterior urethral rupture. 27 Patients underwent a primary urethral repair
      (63%), 13 patients underwent a cistostomy with later urologic reconstruction
      (30%), in 3 patients (7%) other surgical procedures were made. Overall
      complication rate was 39.5%. These complications were: Urethral stenosis, 26
      patients (60.5%), urinary retention secondary to obstruction, 10 patients
      (23.3%), incontinence 10 patients (23.3%) and impotence 7 patients (16.3%).
      Patients treated with a primary urethral repair presented a significantly less
      development of infection, obstruction and stenosis, (p<0.05). Patients with
      pelvis fracture associated to urethral trauma had a significant higher risk of
      developing stenosis and impotence. (p<0.05). CONCLUSIONS: Both different surgical
      techniques compared showed a similar complication and morbidity rates in middle
      follow up. Each procedure should be selected according to clinical condition of
      the patient, the extension of the urethral damage, the associated traumatic
      lesions and the surgeon's expertise. In our searched patients, treated with a
      primary urethral repair we found a significantly less development of infection,
      obstruction and stenosis.

PMID- 19579894
TI  - [Medium-term results of the endourological management with balloon dilatation of
      the ureteropelvic junction stenosis in infants].
AB  - AIM: In the last years it has spread minimally invasive therapeutic for the
      treatment of pyeloureteral junction obstruction in children. Some of them have
      got poor outcomes in 4-year-old minor children. We show our experience in the
      retrograde dilatation with balloon of high pressure in infants. METHODS: It's a
      retrospective study of 16 infants treated in our hospital. The average follow-up
      after the intervention is 27.4 +/- 10.0 months. The diagnostic protocol included
      abdominal ultrasound, cystogram and diuretic renography. The treatment was
      realized by endourology retrograde balloon dilatation under fluoroscopy. The
      balloons were in all the cases semicompliant, with a profile of 5 mm, 6 mm 6 7
      mm. After the expansion there was placed stents type double J with profile and
      length depending on the weight of the patient. To obtain the results, we do
      ultrasound scans and diuretic renography at least 1 year after the intervention.
      RESULTS: The mean duration of the intervention was 36.4 +/- 15.5 minutes. During
      the intervention, in 2 patients the placement of the stent was not possible. The
      time of revenue was 48 hours in all the patients except in 1 of them. The
      analgesic needs were exclusively non steroid antiinflammatorys. The double J
      stent was withdrawn with cystoscopy. In 3 patients there were postoperatory
      complications: a migration of the stent, a urinary infection and an urinoma. In 1
      patient with worsening of hydronephrosis was needed of pyeloplasty. In the
      controls the disappearance of the hydronephrosis was observed in all the cases,
      eliminating likewise the expansion of the renal calyces. The diuretic renography
      improved in all babies, being the boss of the curve normal in 14 cases and semi
      obstructively in 2. The mean time of elimination was 9.8 +/- 2.8 minutes.
      CONCLUSIONS: We think that the balloon dilatation of pyeloureteral junction
      obstruction is a minimally aggressive technique that is possible to realize in
      infants with good results and scanty complications.

PMID- 19579895
TI  - [Metabolic study results of 54 patients with high risk of recurrent urolitiasis].
AB  - INTRODUCTION: Urolithiasis is a metabolic disorder with a tendency to relapse.
      The aim of this study was to assess the prevalence of metabolic abnormalities in
      patients at high risk and the impact of sex and age. MATERIALS AND METHODS:
      Descriptive study of 54 patients (37 men and 17 women), with lithiasic pathology
      at high risk of recurrence. The metabolic study included the measurement of
      calcemia, uricemia, fosfemia, parathormone, calciuria/24 h, uricosuria/24 h,
      fosfaturia/24 h, oxalaturia/24 h, citraturia/24 h and creatinine/24 h. The values
      obtained were corrected according to weight and creatinine. The test used for
      statistical analysis was t-student (STATA 7.0). It was considered significant
      p<0.05. RESULTS: In 64,8% (35/54) of the cases a metabolic abnormality was
      observed and in 27,7% (15/54) there was 2 or more alterations present. The
      metabolic disorders most frequently observed were hypercalciuria (15/54) 27,7%,
      hypocitraturia (15/54) 27,7%, hyperuricemia (8/54) 14,8%. and hyperoxaluria
      (8/54) 14,8%. There was no significant difference in age or sex between the
      groups with and without metabolic abnormality. CONCLUSIONS: Most patients with
      recurrent lithiasic pathology or at high-risk display one or more metabolic
      disorders, being hypercalciuria and hypocitraturia the most frecuently
      encountered. In this study, there was no difference between sexes in most of the
      metabolic disorders, nor in its age distribution. These results demonstrate the
      need for metabolic studies in high-risk patients, since there are tools that
      allow therapeutic medical management of metabolic disorders and thus reduce the
      recurrence of lithiasis.

PMID- 19579896
TI  - [Extraperitoneal bladder rupture coinciding with bone fragments: the case for
      surgical treatment].
AB  - INTRODUCTION: In closed traumatic bladder ruptures, a surgical treatment of the
      intraperitoneal rupture, and a conservative approach to the extraperitoneal one,
      with bladder catheter, antibiotics and confirmation of bladder wound closure
      after two to three weeks-, was recommended. Only recently, attention was paid to
      the importance of the presence of bone fragments of the pelvic fractures, that in
      the vecinity of a bladder catheter or urinary infection may give raise to either
      severe pelvic infection or permanent urinary fistula. PATIENTS AND METHOD: The
      two cases of extraperitoneal bladder rupture here presented, demonstrate the
      difficulties of a secure diagnosis by CT, and the potential severity of the
      existence of bone fragments impronting the bladder disruption. COMMENT: Recent
      consensus on genitourinary trauma emphasizes the need to pay attention to the
      presence of bone fragments of the pelvic ring fractures in cases of closed
      bladder rupture. In cases of extraperitoneal bladder rupture with bone fragments
      in the vecinity, bladder endoscopic examination and surgical treatment may be
      needed.

PMID- 19579897
TI  - [Bowel perforation after radical prostatectomy].
AB  - We report a case of bowel perforation after the accomplishment of a radical
      prostatectomy, the secondary complications to the peritonitis and the resolution
      of the same ones.

PMID- 19579898
TI  - [Extraadrenal retroperitoneal myelolipoma].
AB  - Extraadrenal myelolipomas are rare benign tumors and differentiating them from
      other soft tissue tumors containing fat can be difficult. A retroperitoneal
      myelolipoma adjacent to right renal helium is presented in this case-report.
      Initially oriented as liposarcoma, the final diagnosis was obtained after
      surgery. Computed tomography (CT), ultrasound (US) and magnetic resonance imaging
      (MRI) features may vary according to the major component of the tumor. MRI with
      fat suppression and opposed-phase imaging are the best imaging tools to
      demonstrate the adipose tissue. A histological confirmation may allow a better
      presurgical planification in most cases.

PMID- 19579899
TI  - [Eosinophilic cystitis: review and two case reports].
AB  - Eosinophilic cystitis is a low frequency disease, with less than 200 reported
      cases in the world. It is characterized by a bladder wall inflammation, mainly by
      eosinophils, with fibrosis and muscle necrosis areas. Its origin seems to be
      immunological, although the triggers are not well known. Several predispose
      factor have been described such as allergic diseases, bladder injuries, drugs,
      infections, etc. It affects patient of all ages, mainly adults. It presents with
      frecuency, haematuria and suprapubic pain. Other less frequent symptoms are
      disuria, urinary retention, nicturia, and enuresis. The laboratory study
      (urinalysis, urinalysis and haemogram) and radiology (ultrasound, intravenous
      pyelography, computed tomography and nuclear magnetic resonance) are non
      specific. The lesions observed in the cystoscopy could emulate other diseases,
      that why the proper diagnostic is the histological analysis. The management could
      be observation o antihistaminic, anti-inflammatory and corticoid treatment. In
      refractory cases, surgery is an alternative. In this work, two male adult cases
      are reported with their symptoms, studies and management.

PMID- 19579900
TI  - [Use of M-VAC in the adjuvant treatment of sarcomatoid carcinoma of the bladder].
AB  - Sarcomatoid bladder carcinoma is a high-grade neoplasm and accounts for
      approximately 0,3% of all bladder malignancies. Sarcomatoid carcinoma originates
      from transitional cells of the bladder. Sarcomatoid carcinoma is charactericed by
      a epithelial component and a sarcomatoid component, consisting of spindle cells,
      that is only epithelial marker-positive. We report a 26-year-old woman diagnosed
      of stage III sarcomatoid bladder carcinoma (T3aN0M0) treated with partial
      cistectomy followed by 4 cycles of adjuvant chemotherapy with methotrexate,
      vinblastine, doxorubicin and cisplatin.

PMID- 19579901
TI  - [Assymptomatic prostatic infiltration by chronic lymphocytic leukemia].
AB  - OBJECTIVE: Report of a case of leukemic infiltration of the prostate as an
      incidental CT finding. METHODS: We describe a case of a 60-year-old male
      suffering from chronic lymphocytic leukemia. A routine-performed CT showed
      multiple lymphadenopathies and an hypodense area in the left prostatic lobe. The
      patient was sent to our department to carry out a transrectal ultrasound and
      prostatic biopsy. He didn't relate any urinary symptoms. RESULTS: By the prostate
      rectal examination the gland felt hard and with no well defined limits. The
      transrectal ultrasound showed heterogene parenchyma and several hyperechoic areas
      by a bad circumscribed prostate. The pathological analysis reported a diffuse
      infiltration of the gland by chronic lymphocytic leukemia cells. CONCLUSIONS:
      Although the relapse of hematological tumors to the prostate has been described
      previously, there is no published case to our knowledge of a leukemic prostate
      infiltration in an assymptomatic patient as an incidental finding by an imaging
      procedure.

PMID- 19579902
TI  - [BPH, fight bladder and bladder lithiasis].

PMID- 19579903
TI  - Advances in Latino family research: cultural adaptations of evidence-based
      interventions.
AB  - The stark contrast between frequent calls for research and practice that are
      applicable across a broad spectrum of cultural and ethnically diverse groups and
      the dearth of empirical knowledge about Latino families provided the impetus for
      this special issue on advances in Latino family research. A focus on empirically
      based practice frames the issue, focusing specifically on how concepts (expressed
      emotion, parenting style) can be used within interventions, how Latino parents
      perceive efforts to deliver evidence-based interventions, and how pilot projects
      that delivered culturally adapted interventions in three separate cities impacted
      family functioning. In all, the introduction highlights the complexities for
      researchers in meeting the needs of the field to ensure that effective
      interventions are applicable across cultural groups. Meeting the challenges is
      important to address the need of the growing Latino population. Advances in
      intervention research with ethnic minorities also stand to contribute to the
      advancement of intervention research broadly. This special issue provides
      examples of efforts that are underway to better understand what treatments work
      for Latino families, provided by whom, for what specific problems, and in which
      specific circumstances, paving the way to begin attempting to answer a challenge
      posed more than 40 years ago by Gordon Paul.

PMID- 19579904
TI  - Cultural variability in the manifestation of expressed emotion.
AB  - We examined the distribution of expressed emotion (EE) and its indices in a
      sample of 224 family caregivers of individuals with schizophrenia pooled from 5
      studies, 3 reflecting a contemporary sample of Mexican Americans (MA 2000, N =
      126), 1 of an earlier study of Mexican Americans (MA 1980, N = 44), and the other
      of an earlier study of Anglo Americans (AA, N = 54). Chi-square and path analyses
      revealed no significant differences between the 2 MA samples in rates of high EE,
      critical comments, hostility, and emotional over-involvement (EOI). Only
      caregiver warmth differed for the 2 MA samples; MA 1980 had higher warmth than MA
      2000. Significant differences were consistently found between the combined MA
      samples and the AA sample; AAs had higher rates of high EE, more critical
      comments, less warmth, less EOI, and a high EE profile comprised more of
      criticism/hostility. We also examined the relationship of proxy measures of
      acculturation among the MA 2000 sample. The findings support and extend Jenkins'
      earlier observations regarding the cultural variability of EE for Mexican
      Americans. Implications are discussed regarding the cross-cultural measurement of
      EE and the focus of family interventions.

PMID- 19579905
TI  - Parenting styles in a cultural context: observations of "protective parenting" in
      first-generation Latinos.
AB  - Current literature presents four primary parenting styles: authoritative,
      authoritarian, permissive, and neglectful. These styles provide an important
      shortcut for a constellation of parenting behaviors that have been characterized
      as consisting of warmth, demandingness, and autonomy granting. Empirically, only
      warmth and demandingness are typically measured. Research reporting on parenting
      styles in Latino samples has been equivocal leading to questions about
      conceptualization and measurement of parenting styles in this ethnic/cultural
      group. This lack of consensus may result from the chasm between concepts (e.g.,
      authoritarian parenting) and observable parenting behaviors (e.g., warmth) in
      this ethnic group. The present research aimed to examine parenting styles and
      dimensions in a sample of Latino parents using the two usual dimensions (warmth,
      demandingness) and adding autonomy granting. Traditional parenting styles
      categories were examined, as well as additional categorizations that resulted
      from adding autonomy granting. Fifty first-generation Latino parents and their
      child (aged 4-9) participated. Parent-child interactions were coded with the
      Parenting Style Observation Rating Scale (P-SOS). In this sample, the four
      traditional parenting categories did not capture Latino families well. The
      combination of characteristics resulted in eight possible parenting styles. Our
      data showed the majority (61%) of Latino parents as "protective parents."
      Further, while mothers and fathers were similar in their parenting styles,
      expectations were different for male and female children. The additional
      dimensions and implications are discussed. The importance of considering the
      cultural context in understanding parenting in Latino families is emphasized,
      along with directions for future research.

PMID- 19579907
TI  - Parent-child interaction therapy for Puerto Rican preschool children with ADHD
      and behavior problems: a pilot efficacy study.
AB  - This study evaluates the initial efficacy of the Parent-Child Interaction Therapy
      (PCIT) for Puerto Rican preschool children aged 4-6 years with a diagnosis of
      attention-deficit/hyperactivity disorder (ADHD), combined or predominantly
      hyperactive type, and significant behavior problems. Thirty-two families were
      randomly assigned to PCIT (n = 20) or a 3.5-month waiting-list condition (WL; n =
      12). Participants from both groups completed pretreatment and posttreatment
      assessments. Outcome measures included child's ADHD symptoms and behavior
      problems, parent or family functioning, and parents' satisfaction with treatment.
      ANCOVAs with pretreatment measures entered as covariates were significant for all
      posttreatment outcomes, except mother's depression, and in the expected direction
      (p < .01). Mothers reported a highly significant reduction in pretreatment
      hyperactivity and inattention and less aggressive and oppositional-defiant
      behaviors, conduct problems assessed as problematic, parenting stress associated
      with their child's behavior, and an increase in the use of adequate parenting
      practices. For the WL group, there were no clinically significant changes in any
      measure. Treatment gains obtained after treatment were maintained at a 3.5-month
      follow-up assessment. PCIT seems to be an efficacious intervention for Puerto
      Rican families who have young children with significant behavior problems.

PMID- 19579906
TI  - "Queremos aprender": Latino immigrants' call to integrate cultural adaptation
      with best practice knowledge in a parenting intervention.
AB  - Despite the unique and challenging circumstances confronting Latino immigrant
      families, debate still exists as to the need to culturally adapt evidence-based
      interventions for dissemination with this population. Following the grounded
      theory approach, the current qualitative investigation utilized focus group
      interviews with 83 Latino immigrant parents to explore the relevance of
      culturally adapting an evidence-based parenting intervention to be disseminated
      within this population. Findings from this study indicate that Latino immigrant
      parents want to participate in a culturally adapted parenting intervention as
      long as it is culturally relevant, respectful, and responsive to their life
      experiences. Research results also suggest that the parenting skills participants
      seek to enhance are among those commonly targeted by evidence-based parenting
      interventions. This study contributes to the cultural adaptation/fidelity balance
      debate by highlighting the necessity of exploring ways to develop culturally
      adapted interventions characterized by high cultural relevance, as well as high
      fidelity to the core components that have established efficacy for evidence-based
      parenting interventions.

PMID- 19579909
TI  - Adaptation of the preventive intervention program for depression for use with
      predominantly low-income Latino families.
AB  - This paper describes the process for and safety/feasibility of adapting the
      Beardslee Preventive Intervention Program for Depression for use with
      predominantly low income, Latino families. Utilizing a Stage I model for protocol
      development, the adaptation involved literature review, focus groups, pilot
      testing of the adapted manual, and open trial of the adapted intervention with 9
      families experiencing maternal depression. Adaptations included conducting the
      intervention in either Spanish or English, expanding the intervention to include
      the contextual experience of Latino families in the United States with special
      attention to cultural metaphors, and using a strength-based, family-centered
      approach. The families completed preintervention measures for maternal
      depression, child behavioral difficulties, global functioning, life stresses, and
      an interview that included questions about acculturative stressors, resiliency,
      and family awareness of parental depression. The postintervention interview
      focused on satisfaction, distress, benefits of the adapted intervention, and
      therapeutic alliance. The results revealed that the adaptation was nonstressful,
      perceived as helpful by family members, had effects that seem to be similar to
      the original intervention, and the preventionists could maintain fidelity to the
      revised manual. The therapeutic alliance with the preventionists was experienced
      as quite positive by the mothers. A case example illustrates how the intervention
      was adapted.

PMID- 19579910
TI  - Commentary: On the wisdom and challenges of culturally attuned treatments for
      Latinos.
AB  - In this commentary, I outline the common and distinctive components in the
      cultural adaptation studies in this special issue and compare cultural
      adaptations with universalistic and culture-specific perspectives. The term
      cultural attunement may be more reflective than cultural adaptation insofar as
      the cultural additions in these studies make the treatments more accessible by
      adding language translation, cultural values, and contextual stressors. These
      additions most likely enhance the level of engagement and retention in therapy
      for Latino families. The work ahead requires a deeper examination of the cultural
      theories of psychological distress and the cultural theories of change in
      therapy. A final proposal is made in this commentary for considering the
      bicultural aspects of the cultural adaptation or attunement enterprise, insofar
      as the clinical research encounters with immigrants are bicultural encounters.
      These encounters can reach beyond the notion of cultural "adaptation" of
      mainstream evidence-based treatments to ethnic minorities and present a unique
      opportunity for mutually enriching bicultural integration of theory, research,
      and practice.

PMID- 19579908
TI  - Culturally informed and flexible family-based treatment for adolescents: a
      tailored and integrative treatment for Hispanic youth.
AB  - The increasing utilization of evidence-based treatments has highlighted the need
      for treatment development efforts that can craft interventions that are effective
      with Hispanic substance abusing youth and their families. The list of evidence
      based treatments is extremely limited in its inclusion of interventions that are
      explicitly responsive to the unique characteristics and treatment needs of young
      Hispanics and that have been rigorously tested with this population. Some
      treatments that have been tested with Hispanics do not articulate the manner in
      which cultural characteristics and therapy processes interact. Other treatments
      have emphasized the important role of culture but have not been tested
      rigorously. The value of well designed interventions built upon an appreciation
      for unique patient characteristics was highlighted by Beutler et al. (1996) when
      they argued that "psychotherapy is comprised of a set of complex tasks, and
      practitioners need comprehensive knowledge of how different processes used in
      psychotherapy interact with patient characteristics in order to make treatment
      decisions that will maximize and optimize therapeutic power" (p. 30). A focus on
      how treatment processes interact with patient characteristics is particularly
      relevant in the Hispanic population because of the considerable heterogeneity
      beneath the Hispanic umbrella. Our new program of clinical research focuses on
      articulating how the varied profiles with regard to immigration stressors,
      acculturation processes, values clashes, sense of belonging to the community,
      discrimination, and knowledge about issues important to adolescent health can be
      more effectively addressed by a culturally informed treatment.

PMID- 19579912
TI  - Morpho-histological study of kidney in farmed juvenile beluga, Huso huso
      (Linnaeus, 1758).
AB  - In this study, structure, size and distribution of nephron cells on kidney in
      Huso huso were investigated. The head, body and caudal part of kidney in juvenile
      Huso huso were sampled: The kidney of Huso huso consisted of glomerulus,
      proximal, distal and collecting tubule cells. The average area in 1- and 2-year
      old sturgeon were 2718.07 +/- 1387.51 and 2793.89 +/- 1348 microm in proximal
      cells, 2678.80 +/- 1249.12 and 2599.98 +/- 1428.13 microm in distal cells,
      2275.44 +/- 1289.52 and 2312.23 +/- 1629.58 microm in collecting tubule cells,
      4359.8 +/- 1573.59 and 5071.04 +/- 1916.87 microm in glomerulus and 6019.68 +/-
      1800.55 and 8307.49 +/- 2073.53 microm in Bowman's capsule, respectively. Average
      long and small diameter in 1 and 2 year were 68.03 +/- 17.82 and 49.94 +/- 12.73,
      63.29 +/- 16.15 and 45.58 +/- 12.46 microm in proximal cells, 63.25 +/- 16.01 and
      44.3 +/- 15.09, 63.514 +/- 15.25 and 45.46 +/- 13.3 microm in distal cells, 51.9
      +/- 13.04 and 40.54 +/- 12.21, 57.08 +/- 16.7 and 45.53 +/- 15.28 microm in the
      collecting tubule cells, 91.18 +/- 17.93 and 68.72 +/- 16.22, 98.7 +/- 21.85 and
      72.24 +/- 17.48 microm in glomerulus and 99.32 +/- 19.82 and 76.45 +/- 1896,
      125.44 +/- 24.93 and 93.85 +/- 24.78 microm in Bowman's capsule, respectively. In
      all cases no statistically significant difference detected in the measured cells
      among 1- and 2-year-old fishes. Morpho-histological pattern of kidney can be
      developed on the basis of size, feature and distribution of cells in farmed
      Sturgeon.

PMID- 19579911
TI  - Postsynaptic alpha 2-adrenoceptors mediate melanosome aggregation in melanophores
      of the white-spotted rabbitfish (Siganus canaliculatus).
AB  - The present investigation was undertaken to study the nature of neuro-melanophore
      junction in the white-spotted rabbit fish Siganus canaliculatus. In vitro
      experiments using split fin preparation indicated that melanophores of S.
      canaliculatus are highly responsive to potassium ions and adrenergic agonists.
      Potassium ions and the adrenergic agonists induced prompt melanosome aggregation
      that could be competitively blocked by yohimbine (alpha-2 specific adrenergic
      antagonist) and phentolamine (non-specific alpha adrenergic antagonist). The
      melanophore responses to repeated potassium stimulation (up to 20 stimuli) did
      not show any sign of fatigue. However, statistically significant enhancement was
      observed in responses to potassium that followed the first five stimulations.
      Adrenergic agonists acted in a time and concentration-dependent manner and their
      relative potency had the following rank order: clonidine (alpha-2 specific
      agonist) > norepinephrine (non-specific adrenergic agonist) > phenylephrine
      (alpha-1 specific agonist) > methoxamine (alpha-1-specific agonist). Yohimbine
      exerted a more potent inhibiting effect on norepinephrine induced melanosome
      aggregation compared to phentolamine. Prazosine (alpha-1 specific antagonist) had
      no effect on such aggregation. Chemically denervated melanophores displayed
      hypersensitivity to alpha-adrenergic agonists but were refractive to potassium
      ion stimulation. The refractivity of denervated melanophores to potassium
      indicates the effect of potassium ion is not direct on melanophores but it is
      rather through depolarization effect of potassium on the neuro-melanophore
      peripheral sympathetic fibers and hence release of norepinephrine. In denervated
      melanophores, similar to intact melanophores, only phentolamine and yohimbine but
      not prazosine, significantly inhibited melanosome aggregation effect of
      norepinephrine, indicating that norepinephrine effect is through postsynaptic
      alpha-2 adrenoceptors. The present data demonstrate that the nature of
      melanophore innervation in this teleost is adrenergic and neuro-melanophore
      signals mediating melanosome aggregation are transmitted through alpha-2
      postsynaptic adrenoceptors.

PMID- 19579913
TI  - Effects of methyl-beta-cyclodextrin and cholesterol on cryosurvival of
      spermatozoa from C57BL/6 mouse.
AB  - MBCD and Cholesterol-Loaded-Cyclodextrin (CLC) were examined for their abilities
      to increase the cryosurvival of C57BL/6 mouse sperm, the main strain of
      genetically engineered mice. The intactness of acrosome and motility of
      frozen/thawed spermatozoa were used to monitor cryosurvival. In this experimental
      study, male mice were randomly divided in 6 groups: control 1, experimental 1,
      experimental 2, control 2, experimental 3 and experimental 4. In experimental
      groups 1 and 2 spermatozoa were exposed to 0.75 and 1 mM MBCD and in experimental
      groups 3 and 4 were exposed to two different concentrations of CLC (1 and 2 mg
      mL(-1)) over a period of 1 h and were subsequently cryopreserved. Spermatozoa in
      control 1 group were frozen without any exposure to CLC or MBCD and in control 2
      (vehicle), sperms were incubated with 4 mM MBCD. The post-thaw sperms were
      evaluated for their motility and acrosomal status. The values of the intact
      acrosome and motility increased significantly with concentration of CLC compared
      to controls and MBCD experimental groups (p<0.05). These results indicate that
      cryosurvival of C57BL/6 mouse spermatozoa is enhanced by exposure to MBCD which
      loaded with cholesterol (CLC) before freezing and MBCD alone can not protect
      sperm from freeze-thaw damage efficiently compare to CLC.

PMID- 19579914
TI  - Screening plant growth promoting rhizobacteria for improving seed germination,
      seedling growth and yield of maize.
AB  - The effect of Plant Growth-Promoting Rhizobacteria (PGPR) on seed germination,
      seedling growth and yield of field grown maize were evaluated in three
      experiments. In these experiments six bacterial strains include P. putida strain
      R-168, P. fluorescens strain R-93, P. fluorescens DSM 50090, P. putida DSM291, A.
      lipoferum DSM 1691 and A. brasilense DSM 1690 were used. Results of first study
      showed seed inoculation significantly enhanced seed germination and seedling
      vigour of maize. In second experiment, leaf and shoot dry weight and also leaf
      surface area significantly were increased by bacterial inoculation in both
      sterile and non-sterile soil. The results showed that inoculation with bacterial
      treatments had a more stimulating effect on growth and development of plants in
      nonsterile than sterile soil. In the third experiment, Inoculation of maize seeds
      with all bacterial strains significantly increased plant height, 100 seed weight,
      number of seed per ear and leaf area. The results also showed significant
      increase in ear and shoot dry weight of maize.

PMID- 19579915
TI  - The effects of lamotrigine on the acquisition and expression of morphine-induced
      place preference in mice.
AB  - The purpose of the present study is to determine the effects of the
      anticonvulsant drug, lamotrigine, on the acquisition and expression of morphine
      induced place preference in mice. Lamotrigine prevents the release of glutamate
      from presynaptic neurons and inhibits action potential in postsynaptic area by
      inhibiting presynaptic sodium and calcium channels. Because of such properties,
      lamotrigine is used for reducing craving for and use of cocaine, alcohol and
      abused inhalant. So, to determine the effects of lamotrigine on opiates;
      specifically morphine, 180 male Swiss-Webster mice (20-35 g) were used in this
      study. Conditioned place preference, was assessed using a biased place
      conditioning paradigm. In a pilot study the effects of various doses of morphine
      (2.5, 5 and 10 mg kg(-1)), alone, or in combination with lamotrigine (1, 5 and 25
      mg kg(-1)) on the place conditioning paradigm were examined. Animals were
      injected with the aforementioned doses of lamotrigine 60 min either prior to each
      morphine injections (acquisition) or prior to the start of the expression on the
      test day (expression). Administration of different doses of morphine (2.5, 5 and
      10 mg kg(-1)) induced conditioned place preference whereas the administration of
      different doses of lamotrigine (1, 5 and 25 mg kg(-1)) failed to induce place
      preference. Acquisition and expression of morphine-induced CPP were reduced by
      lamotrigine at doses of 1, 5 and 25 mg kg(-1) and 5 and 25 mg kg(-1),
      respectively. Physiological mechanisms of action of lamotrigine and its potential
      therapeutic use in the treatment of drug-dependence are discussed.

PMID- 19579916
TI  - Effect of intrahippocampal injection of aluminum on active avoidance learning in
      adult male rats.
AB  - Aim of this research was to study the effect of intrahippocampal injection of
      different doses of AlCl3 in adult male rats on active avoidance learning. Thirty
      five adult male Wistar rats (250-300 g) were used into five groups: (1) Control,
      (2) Test-I received daily 1 microL AlCl3 1%, pH = 7.2, 3); Test-II received daily
      1 microL AlCl3 0.5%, pH = 3.4, 4); Sham-I received daily 1 microL aCSF, pH = 7.2,
      5); Sham-II received daily 1 microL aCSF, pH = 3.4. All rats in test and sham
      groups treated 10 min before training. Animals were anaesthetized with ketamine
      HCl/xylazine (90/10 mg kg(-1) b.wt.(-1), i.p.) and underwent a stereotaxic
      surgery for implant of two stainless steel guide cannula into the hippocampus
      bilaterally. Every day 10 min after above treatments all rats were used to assess
      the spatial learning performing using Y-maze. Criterion Correct Response (CCR)
      was 90% in last session of training. There were no significant differences
      between training sessions to receiving CCR in control, Sham-I and Sham-II groups.
      Cognition in animals received AlCl3 1%, pH = 7.2 was impaired significantly with
      compare to other groups (*p<0.0001). Present results show that intrahippocampal
      injection of AlCl3 1%, causes active avoidance learning impairment significantly.
      The exact mechanism of Al3 effect on brain and cognition is remains unknown.

PMID- 19579917
TI  - Role of angiotensin converting enzyme, paraoxonase 1 55, 192 gene polymorphisms
      in syndrome X and coronary heart disease.
AB  - Aim of this study was to investigate the possible relationship between ACE and/or
      PON1 M55L, Q192R genetic polymorphisms and subjects with Coronary Heart Disease
      (CHD) and/or syndrome X (SX) when compared to the control group. ACE I/D, PON1
      M55L and Q192R genetic polymorphisms, Body Mass Index (BMI) and biochemical
      parameters were investigated in subjects with CHD (n = 19), SX (n = 34) and
      healthy subjects (n = 26). All of the subjects were nonsmokers. According to the
      unrelated group t-test results; BMI, HDL-C and TG values were found to be
      slightly different in SX and control subjects but there was no significant
      difference in LDL-C and TC values. According to the Mann Whitney U-test results,
      BMI, TC, HDL-C and LDL-C values were found to be significantly different among
      CHD and control group subjects, but there was no difference in TG values. The
      results of this study indicates that ACE, PON1 192 and PON1 55 gene polymorphisms
      are not related to genetic susceptibility to SX and/or CHD in non-smokers.
      Obviously, the interpretation of these finding is difficult due to the small
      sample size and larger group studies are needed for more definitive conclusions.

PMID- 19579918
TI  - Effect of dietary antibiotic, probiotic and prebiotic as growth promoters, on
      growth performance, carcass characteristics and hematological indices of broiler
      chickens.
AB  - This experiment was conducted for comparison the effects of antibiotic
      (flavomycin), probiotic (primalac), prebiotic (Biolex-MB) and mixture ofprobiotic
      and prebiotic (primalac plus Biolex-MB) as dietary growth promoter on growth
      performance, carcass characteristics and hematological indices of broiler
      chickens. Three hundred day old Ross 308 broilers were equally distributed into
      30 floor pens and reared for 42 day. A basal diet was formulated covering the
      recommendations of NRC (1994) for starter (0-21 days) and grower (22-42 days)
      periods and considered as control diet. Four tested diets were formulated by
      supplemented the basal control diet with antibiotic (flavomycin), probiotic
      (primalac), prebiotic (Biolex-MB) and mixture ofprimalac plus Biolex-MB,
      respectively. Six replicates were used for each treatment. The results of present
      study showed that all growth promoters used was improved growth indices of Ross
      308 broilers. The highest significant (p<0.05) values of carcass and thigh were
      recorded for broilers fed diet supplemented with flavomycin. The highest (p>0.05)
      value of breast was recorded for broilers fed the diet supplemented with
      primalac, meanwhile the lower value were showed for birds fed either diet or diet
      supplemented with Biolex-MB. The percent of carcass and cuts followed the same
      trend. Hematological parameter including cholesterol was recorded the highest
      (p>0.05) values groups fed the diets either control or supplemented with
      flavomycin, meanwhile the lower value was showed for bird fed diet supplemented
      primalac plus Biolex-MB. Triglycerides and very low density lipoprotein
      cholesterol (VLDL) were recorded the highest concentration for bird fed both
      control and diet supplemented with flavomycin groups while least concentration
      was found for bird fed diet supplemented with primalac. The results of present
      study revealed that probiotic and prebiotic as growth promoters can use as
      alternatives non-antibiotic feed additives to their free harmful side effects on
      the consumers and to improve broiler chickens growth indices.

PMID- 19579919
TI  - Antifungal activity of nettle (Urtica dioica L.), colocynth (Citrullus
      colocynthis L. Schrad), oleander (Nerium oleander L.) and konar (Ziziphus spina
      christi L.) extracts on plants pathogenic fungi.
AB  - Anti-mycotic activity of the ethanol extracts from Nettle (Urtica dioica L.),
      Colocynth (Citrullus colocynthis L. Schrad), Konar (Ziziphus spina-christi L.)
      and Oleander (Nerium oleander L.) floral parts were screened in vitro against
      four important plant pathogenic fungi viz.; Alternaria alternate, Fusarium
      oxysporum, Fusarium solani and Rizoctonia solani using agar dilution bioassay.
      Extracts showed antifungal activity against all the tested fungi. Among the
      plants, Nettle and Colocynth were the most effective against A. alternate and R.
      solani while Oleander possesses the best inhibition on F. oxysporum and F.
      solani. Konar was the most effective extract by reducing the growth of Rizoctonia
      solani than other fungi. These results showed that extracts could be considered
      suitable alternatives to chemical additives for the control of fungal diseases in
      plants.

PMID- 19579920
TI  - Evaluation of vaginal misoprostol effect on pregnancy rate after intrauterine
      insemination.
AB  - The goal of this study was to evaluate the effect ofmisoprostol on pregnancy rate
      after intrauterine insemination. This randomized double blind clinical trial
      study was performed on 66 (33 cases and 33 controls) infertile women who referred
      to infertility center of Imam Khomeini Hospital Sari, Iran for intrauterine
      insemination during 2006-2007. The two groups were matched for age, infertility
      causes and BMI. After intrauterine insemination, 200 mcg misoprostol was placed
      in posterior fornix of case group and a similar placebo tablet in control group.
      Chemical and clinical pregnancies and complications were recorded. Results were
      analyzed by means of SPSS 11 software, paired t-test and student t-test. The p
      values of less than 0.05 were considered to be statistically significant.
      Chemical pregnancy (positive BHCG) occurred in 6 patients (18.2%) in each group.
      Clinical pregnancy occurred in 5 patients (15.15%) in case and 6 patients (18.2%)
      in controls. There were no significant statistical differences in complications
      between the two groups. Vaginal misoprostol after intrauterine insemination does
      not improve pregnancy rate.

PMID- 19579921
TI  - Investigation on the effect of supplementing rumen-protected forms of methionine
      and choline on health situation and reproductive performance of Holstein dairy
      cows.
AB  - Twenty Holstein dairy cows in their first and second lactation were used from 4
      week prepartum through 20-week postpartum. The aim was to investigate the effect
      of feeding different levels of ruminally protected methionine and choline on
      health situation and reproductive indices of Holstein dairy cows. Cows were
      randomly assigned to receive one of the following treatments: 18 g day(-1) of
      rumen protected methionine (RPM), 60 g day(-1) of rumen protected choline (RPC),
      18 g day(-1) of RPM + 60 g day(-1) of RPC and neither supplement (control). The
      treatments significantly affected services per conception and open days of
      lactating dairy cows, but did not significantly affect on days to first estrus
      and number of pregnant cows. RPM + RPC-fed cows had the lowest open days, days to
      first estrus and services per conception compared with other groups. Although no
      statistical differences were noted for any given health category, the overall
      incidence of health-related disorders was numerically lowest for cows fed RPM +
      RPC. Results indicate that the supplementation of RPM and RPC have been improved
      reproductive performance and health situation of dairy cows.

PMID- 19579922
TI  - Use of leisure time in cardiovascular patients in Gorgan (south east of Caspian
      Sea).
AB  - The aim of this study was to compare activity patterns and leisure time between
      matched groups of patients with cardiovascular disease and individuals without a
      heart disease. The study included 100 patients recruited from those referred to
      cardiology department of 5th Azar General Hospital of Golestan University of
      Medical Sciences in Gorgan (South East of Caspian Sea) and 100 matched control
      subjects during the period 2007-2008. Odds ratios (OR), together with 95%
      confidence intervals (95% CI), were calculated using logistic regression, as
      estimates of relative risks. Listening to music OR = 8.800 (95% CI: 2.717-28.499,
      p<0.05), meditation OR = 6.111 (95% CI; 2.616-14.274, p<0.05) were independent
      risk factors. Subjects who performed 2 h per week and 2-4 h per week physical
      activity, the odds ratios were 0.038 (95% CI: 0.012-0.124, p<0.05) and 0.079,
      (95% CI: 0.024-0.260, p<0.05), respectively. Low physical activity and use of
      long time relaxation are associated with cardiovascular disease in these
      patients. Regular participation in physical activity such as walking 2 h per week
      and 2-4 h per week, are associated with reduced risk of cardiovascular disease.
      This study suggests the importance of both leisure-time physical activity and
      sedentary behaviors in the prevention of CVD.

PMID- 19579923
TI  - A breeding program for balanced improvement of performance and health in
      broilers.
AB  - To illustrate the consequences of including health related traits in a
      sustainable broiler breeding program, two scenarios were simulated using the
      SelAction program. In the first scenario (economic), selection was only for
      production traits and Gait Score (GS) and Heart Failure (HF) were ignored in the
      breeding goal. In the second scenario (sustainable), GS and HF as well as
      production traits were included in the breeding goal. Economic values of GS and
      HF were determined using desired-gain approach to obtain a zero response in GS
      and HF. The results indicate that, despite improved responses for production
      traits in the economic scenario, there was an unfavorable reduction in GS of
      about 0.13 points and an unfavorable increase in HF of about 0.025 points. In the
      sustainable scenario, the deterioration of GS and HF was stopped. In the economic
      scenario with zero economic values for GS and HF, the total monetary response was
      higher (0.104 euros) than sustainable scenario (0.097 euros). Due to negative
      correlations between health and production traits, increased emphasis on health
      traits in the sustainable scenario resulted in a reduction in the total monetary
      response. In conclusion to stop the increased incidence of diseases, health
      traits should be included in the breeding goal and assigned appropriate values.

PMID- 19579924
TI  - Survey of factors effective on outcome of weaning from mechanical ventilation.
AB  - This study was aimed to recognize factors effective on weaning from mechanical
      ventilation and determine the reasons of unsuccessful Spontaneous Breathing Trial
      (SBT) and reintubation. The study population consisted of 202 critically ill
      pediatric patients who received mechanical. When the patient was enrolled in the
      study, mechanical ventilation support was stopped and the patient underwent a 2 h
      trial of Spontaneous Breathing Trial (SBT), at the end of the trial if PaCO2 was
      in normal range was extubated. Of the 202 patients who underwear SBT, 141
      attempts had successful trial. The remaining 61 patients had sign of poor
      tolerance during the trial of spontaneous breathing and were reconnected to the
      ventilator. One hundred and forty one patients (69.8%) successfully passed the
      trial. 17 (12%) of above mentioned group required reintubation within 48-72 h.
      The overall success and failure rate was 61.3 and 38.7%, respectively. Mortality
      rate in patients who did not tolerate SBT or were extubated, or required
      reintubation were 13% (8 patients), 11.3% (14 patients) and 23.5% (4 patients),
      respectively. The most common reasons for reintubation were neuromuscular disease
      (58.8%) congenital cardiac disease (23.5%) and aspirative pneumonia (17.6%). The
      finding indicates that two third of intubated patients, respond successfully to
      SBT and could be extubated and the neuromuscular diseases is the main cause of
      reintubation.

PMID- 19579925
TI  - In vitro antimicrobial and cytotoxic activities of leaves and flowers extracts
      from Lippia alba.
AB  - The research was conducted to investigate the in vitro antimicrobial and
      cytotoxic activities of leaves and flowers extract extracted from Lippia alba.
      Disc diffusion technique was used for in vitro antibacterial and antifungal
      screening. Zones of inhibition were observed in disc diffusion for antibacterial
      screening against 4 Gram-positive pathogenic and 6 Gram-negative pathogenic
      bacteria. Among crude extracts chloroform extract showed good activity against
      all test organisms. A Large zone of inhibition was observed (18 mm) against
      Vibrio parahaemolyticus. In antifungal screening, the compound showed mild to
      moderate zones of inhibition against four tested organisms. A Large zone of
      inhibition was observed against Aspergillus niger (13 mm). Cytotoxic activities
      of crude extracts were determined using Brine shrimp lethality Bioassay and LC50
      values of standard Vincristin sulphate as positive control, n-hexane and crude
      ethanol extracts were found to be 5, 15 and 20 microg mL(-1), respectively.

PMID- 19579926
TI  - Effect of lactoferrin and iron on the growth of human pathogenic Candida species.
AB  - Effect of lactoferrin and iron have been studied on the multiplication and
      pseudohyphae production by three pathogenic Candida species viz., C. albicans, C.
      krusei and C. tropicalis. Results showed that lactoferrin showed significant
      antifungal effect on the three species tested, while the addition of iron enhance
      the multiplication of Candida species.

PMID- 19579927
TI  - Ultrasound findings in biliary atresia: the role of triangular cord sign.
AB  - In this prospective study, 49 infants with prolonged jaundice, were studied
      between January 2005 to April 2007 in Tabriz Children's Hospital. All of these
      infants were evaluated with ultrasonography and isotopscan and finally biopsy was
      done in all of them under guide of sonography. In their sonographic evaluation,
      absence or presence of gall bladder, its size and also its evacuation after
      feeding was checked and beside this triangular cord sign was controlled. The PPV
      and specificity of triangular cord sign in diagnosis of extrahepatic biliary
      atresia (EHBA) was 100% but its NPV was only 78.5%. The overall accuracy, PPV,
      NPV, specificity and sensitivity ofultrasonographic findings in diagnosis of EHBA
      was about 94, 92, 94, 97 and 86%. Ultrasonography is a reliable screening method
      in early diagnosis of EHBA and triangular cord sign increases its accuracy
      especially its specificity.

PMID- 19579928
TI  - Correlation of cyclooxygenase 2 expression and inflammatory cells infiltration in
      colorectal cancer.
AB  - This study want to determine correlation of cyclooxygenans 2 (Cox-2) expression
      and inflammatory reaction in colorectal carcinoma. Archival H and E slides of 150
      patients with primary colorectal carcinoma were reviewed to confirm pathological
      feature and to select suitable tissue blocks for immunohistochemical staining
      with mouse monoclonal antibody against human Cox-2 and various inflammatory
      cells. After scoring, statistical analysis were carried out with SPSS software,
      chi2 methods and bivariate pearson correlation analysis. The expression of Cox-2
      (grade 3 to 7) in 71.3% of patients associated with mast cells, neutrophils,
      eosinophils, macrophages, CD3+ lymphocytes infiltration was significant (p =
      0.001). Correlation of Cox-2 expression associated with CD8+ lymphocytes
      infiltration was not significant (p = 0.569). Also CD3+ lymphocytes show severe
      infiltration when the expression of Cox-2 is negative (p<0.05). The main purpose
      of this study was to evaluate the interaction between the Cox-2 expression and
      inflammatory cells infiltration. This study showed that there is a close
      relationship of Cox-2 expression and mast cells, neutrophils, eosinophils,
      macrophages and CD3+ lymphocytes. The only exception was CD8+ lymphocytes. It is
      may be due to independent role of anti tumoral effect of this inflammatory cells.

PMID- 19579929
TI  - Genetic transformation of Nepalese spring wheat (Triticum aestivum L.) cultivars
      with ipt gene under the regulation of a senescence enhanced promoter from maize.
AB  - Two Nepalese spring wheat cultivars were transformed with an ipt gene from
      Agrobacterium tumefaciens under the control of the senescence inducible promoter
      pSEE1 from maize using biolistic method. The resulting transgenic lines, one from
      Pasang Lahmu and seven from Annapurna-1, were studied for the expression of the
      transgene and the phenotype characters like chlorophyll content, chlorophyll a/b
      ratio, PS II quantum yield and other parameters of agronomic importance. Analysis
      of transgene expression by RT-PCR revealed very weak or no signal at all,
      indicating either partial or complete silencing of the transgene in the lines
      tested. None of the plants exhibited a phenotype that was significantly different
      from the respective azygous controls.

PMID- 19579930
TI  - Blue light signaling inactivates the mating type genes-mediated repression of
      asexual spore production in the higher basidiomycete Coprinopsis cinerea.
AB  - Monokaryotic mycelia of several wild-type strains of the homobasidiomycete
      Coprinopsis cinerea form abundant numbers of oidia both in the light and dark due
      to the regulation of oidia production by the A and B mating type genes.
      Nevertheless, little is known about whether and how the mating type loci and
      light signal regulate the oidiation in C. cinerea. Herein, the experimental
      results demonstrated that the self-compatible homokaryon AmutBmut strain, the
      mycelia whose nuclei carry mutations in both the A and B loci, can produce only a
      few oidia in the dark, whereas the formation of numerous numbers of oidia is
      induced by the light. The semi-compatible homokaryon AmutB, but not ABmut, has
      the production and behavior of oidia formation similar to those of AmutBmut.
      These findings indicated that in AmutBmut strain the mutation at the A locus
      results in repression of oidiation in the dark and the blue light alleviates this
      effect, whereas the mutated B genes function has no effects. Since, the oidia
      production relies on both A and light signal, it is possible that A locus might
      be linked to the blue light receptor genes. The present results demonstrated for
      the first time that the secondary hyphal knot formation (skn1), fruiting body
      maturation (mat) and basidiospore formation (bad) genes which are essential in
      the C. cinerea fruiting pathway are not involved in the regulation of asexual
      sporulation. In addition, the positive light effect on oidiation could also occur
      in C. cinerea dikaryons.

PMID- 19579931
TI  - Difference in leptin hormone response to nutritional status in normal adult male
      albino rats.
AB  - The present study investigated the effect of 14 days diet, enriched in butter,
      vitamin E (vit. E) and green tea, on the major regulators of energy expenditure.
      Leptin is the product OB gene. This 16 KDa protein is produced by mature
      adipocytes and is secreted in plasma. Its plasma levels are strongly correlated
      with adipose mass in rodents as well as in humans. Leptin inhibit food intake,
      reduces body weight and stimulates energy expenditure. In order to evaluate the
      effect of diet enriched in butter, vit. E and green tea on body weight, adipose
      tissue weight and organs weight, serum lipids, lipoproteins content and serum
      leptin levels in male albino rats supplemented for 14 days on the previous diet.
      This study showed that high fat diet significantly increased body weight and
      adipose tissue weight, while vit. E and green tea enriched diet significantly
      lowered body weight and adipose tissue weight, kidney and spleen weights didn't
      show significant changes in all the experimental groups. While liver weight
      decreased in diet supplemented with high fat diet. Also, the results showed that
      high fat diet and vit. E supplemented diet induced significant increase in total
      cholesterol, LDLc., triglyceride level with significant decrease in HDLc. level
      as compared to normal control rats. Finally green tea supplemented diet induced
      significant decrease in total cholesterol, LDLc., triglyceride level with
      insignificant increase in HDLc. level in control rats. On the other hand, high
      fat supplemented diet significantly increased serum leptin levels in rats
      compared to control group, while vit. E and green tea enriched diet significantly
      lowered serum leptin levels at the end of experimental period. In conclusion,
      improving the biological activity of leptin by diet modification may exist as a
      practical strategy for the treatment of obesity and related disorders and a diet
      rich in green tea to reduce the risk of cardiovascular disease (CVD) obesity and
      also protect the liver against free radicals.

PMID- 19579932
TI  - Enhancement of growth and nutrient uptake of rapeseed (Brassica napus L.) by
      applying mineral nutrients and biofertilizers.
AB  - For investigating the effect of chemical fertilizer as well as biofertilizers on
      seed yield and quality i.e. oil, protein and nutrients concentration of rapeseed
      (Brassica napus L.), a split-plot fertilizers application experimental design in
      4 replications was carried out during the 2005-2006 growing season, at the
      Gharakheil Agricultural Research Station in the Mazandaran province of Iran.
      Rapeseed was grown as a second crop in rotation after rice. Biofertilizers
      treatments were two different levels: control (no seed inoculation) and seeds
      inoculation with a combination of Azotobacter chroococcum and Azosprillum
      brasilense and Azosprillum lipoferum, as main plot and chemical fertilizers
      comprised N, P, K and their combinations, NPKS and NPK Zn as sub plots. The
      maximum value of seed yield obtained at (BF+NPK Zn) 3421.2 kg h(-1) corresponding
      to 244.5 pods per plant and maximum concentration of Zn in leaves as well as
      seeds. The highest weight of 1000 seeds (4.45 g) happened to obtain at (BF+NPK S)
      which coinciding with the maximum K levels in leaves. The highest number of
      branches was obtained at (BF+NPK Zn) with 4.43 branches per plant i.e., 46.2%
      increase over the control. The maximum value of rapeseed oil content 47.73%
      obtained at T16 (BF+NK) but maximum protein concentration of seed obtained at T12
      (BF+N). Overall the results indicated that inoculation resulted in increase in
      seeds yield (21.17%), number of pods per plant (16.05%), number of branches
      (11.78%), weight of 1000 grain (2.92%), oil content of seeds (1.73%) and protein
      (3.91%) but decrease (-0.24%) in number of seeds per pods comparing to non
      Biofertilizers treatments. Irrespective to the treatments, results showed that
      application of Biofertilizers coincided with 3.86, 0.82, 2.25, 0.75 and 0.91%
      increase in concentrations of N, P, K, S and Zn in the seeds over the non
      Biofertilizers treatments.

PMID- 19579933
TI  - Effects of the seminal plasma zinc content and catalase activity on the semen
      quality of water buffalo (Bubalus bubalis) bulls.
AB  - In order to determine zinc and catalase content of seminal plasma in the buffalo
      and to study their associations with the semen characteristics, 54 semen samples
      were collected from 10 buffalo bulls; semen volume and sperm concentration, gross
      and progressive motility and viability were evaluated, seminal plasma was then
      harvested by centrifugation and its zinc content was estimated by atomic
      absorption spectrophotometer and its catalase activity determined by using a
      commercial kit. The zinc content of the seminal plasma (Mean +/- SEM) was
      recorded as 154.40 +/- 1.74 mg L(-1), while, the mean catalase value was 32.00 +/
      0.42 U mL(-1). The mean zinc values was highly correlated with sperm progressive
      motility and viability and with catalase values (p = 0.000 for all) and also was
      associated with gross motility (p = 0.020) and negatively with abnormal
      morphology (p = 0.049). The catalase values were highly associated with sperm
      progressive motility, viability and zinc content (p = 0.000 for all) and was
      associated with sperm gross motility (p = 0.024). For further clarification of
      these correlations, the samples were categorized in three groups of excellent
      (Ex, >90% motile, n = 33), good (Go, 80-89% motile, n = 15) and moderate (Mo,
      <79% motile, n = 6) according to their percentage of sperm motility. The mean
      progressive motility in Ex group was 92.54 +/- 0.51%, in Go group was 81.66 +/-
      0.62% and in Mo group was 71.66 +/- 1.05%. The mean zinc and catalase values were
      recorded as 161.07 +/- 1.63 mg L(-1) and 33.41 +/- 0.34 U mL(-1) in Ex, 146.70 +/
      1.91 mg L(-1) and 31.01 +/- 0.67 in Go and 136.42 +/- 4.97 mg L(-1) and 26.51 +/
      0.87 U mL(-1) in Mo groups. The mean zinc value in Ex group was highly
      associated with sperm motility, viability and catalase values, in Go group was
      associated with catalase values and highly associated with sperm abnormal
      morphology and in Mo group it was highly associations with catalase values only.
      The mean catalase value in Ex group, was highly associated with sperm motility
      and viability, in Go group was associated with zinc content and in Mo groups was
      highly associated with the zinc content. These results show that seminal plasma
      zinc and catalase content are correlated with semen characteristics and
      synergistically act to preserve motility and viability of the spermatozoa after
      ejaculation.

PMID- 19579934
TI  - Plasma glucose lowering effect of the wild Satureja khuzestanica Jamzad essential
      oil in diabetic rats: role of decreased gluconeogenesis.
AB  - This study was to evaluate the effect of the wild SKEO on activities and genes
      expression of hepatic Glycogen Phosphorylase (GP) and phosphoenolpyruvate
      carboxykinase (PEPCK) in normal and diabetic rats. The wild SKEO was orally
      administered at different doses (50 and 100 mg/kg/day) to normal as well as
      diabetic rats for 21 days. The levels of mRNA were determined using the
      quantitative real-time RT-PCR technique. The plasma glucose concentrations of
      diabetic rats receiving SKEO (100 mg kg(-1)) compared with diabetic control were
      significantly decreased. Hepatic GP activity and its mRNA levels of diabetic rats
      treated with SKEO moderately increased. The activity of hepatic PEPCK and its
      mRNA levels were significantly decreased in normal rats treated with SKEO (100 mg
      kg(-1)). The enhancement of PEPCK activity and its mRNA levels of diabetic
      treated rats with SEKO (100 mg kg(-1)) was significantly decreased compared with
      diabetic control. In conclusion, an excessive inhibition of PEPCK in liver of
      diabetic rats treated with the wild SKEO may contribute to the plasma glucose
      lowering action of SKEO that seems to be in relation with antioxidant properties
      of SKEO.

PMID- 19579935
TI  - Gene effects and combining ability in some bread wheat genotypes to yellow rust
      disease.
AB  - Ten wheat lines were studied to determine gene effects and combining ability in
      some bread wheat genotypes to yellow rust disease. Ten parental lines and F1 were
      evaluated in a randomized complete block design with three replications in
      Agricultural and Natural Resources Research Center, Mashhad, Iran. Two races
      (134E134A+ and 4E0A+) were used for this study. Latent Period (LP) and Infection
      Type (IT) were measured in the field and greenhouse. Results showed significant
      differences between races in their pathogenicity and between genotypes in their
      resistance to the pathogen. Diallel cross carried out between the parents and
      progenies and thereafter were analyzed by the method of Griffing and Haymans. The
      General Combining Ability (GCA) and Special Combining Ability (SCA) for all
      traits were significant and showed additive variance was more important. Test for
      validity of diallel hypothesis proved epistasis effect for all traits. P1, P2 and
      F1 showed significant difference between all traits in generations mean analysis.
      Average degree of dominance ranged from partial to over dominance for resistance
      or susceptibility. Dominance, additive and epistatic types of gene action were
      responsible for the genetic control of the traits. However, except for additive
      additive component, non-additive effect of genes could not be fixed by self
      fertilization.

PMID- 19579936
TI  - Genetic diversity of grapevine accessions from Iran, Russia and USA using
      microsatellite markers.
AB  - To discover marker information content and differentiation among grapevine
      accessions from Iran, USA and Russia, nine microsatellite markers were used. A
      total of 75 alleles were detected, giving a mean of 8.3 alleles per 9 loci. The
      total number of alleles per locus varied between 6 to 11 and the polymorphism
      information content ranged from 0.65 to 0.88, indicating that these loci were
      highly informative. A positive correlation (r = 0.870) was observed between the
      number of alleles and the level of polymorphism. Two SSRs loci including
      SSrVrZAG47 and VVMD27 were found to be probably synonymous. Gene diversities were
      high in all populations with values ranging from 0.709 to 0.784. In all
      populations, the mean number (averaged over loci) of heterozygous individuals was
      higher than expected. PCO analysis could not be so clearly differentiated
      accessions from Iran and Russia. The pattern of clustering of the Vitis vinifera
      populations was according to their geographic distribution. It is suggested that
      accessions could possibly be assigned to their regions of origin according to
      their genotypes.

PMID- 19579937
TI  - Effect of salinity on organic solutes contents in barley.
AB  - Salinity (NaCl stress) was applied with 50, 100, 200, 300 and 400 mM NaCl. The
      shoot and root water content and organic solutes contents of two barley varieties
      (Hordeum vulgare L. var. Afzal and var. EMB82-12) were determined in various
      concentrations of NaCl. Soluble sugar and proline contents were increased in two
      barley varieties in response to increased salt concentration, but this increase
      in Afzal var. were higher than EMB82-12. Soluble protein content was decreased in
      two barley varieties in response to different salt regimes and this decrease in
      Afzal var. was lower than EMB82-12 var. RWC decreased with increasing NaCl
      concentrations. Decrease of water content in EMB82-12 plants was higher than
      Afzal plants.

PMID- 19579938
TI  - Molecular analysis for genetic diversity and distance of introduced Grus antigone
      sharpii L. to Thailand.
AB  - The genetic relationship was examined in a population of Grus antigone sharpii L.
      using DNA markers from the ISSR technique for applying towards breeding purposes
      for conservation of species. Since their extinction from Thailand, sixteen
      eastern sarus cranes: Grus antigone sharpii L. provided from Cambodia were fed
      and bred to sixty individuals at Nakhonratchasima Zoo, Northeastern Thailand to
      re-exist in Thai natural sites. Their genetic diversity and distance were
      examined to test their possibility to adapt to environmental variation. Blood
      samples from 27 individuals of Grus antigone sharpii L. were collected and DNA
      was extracted. These DNA samples were amplified using the successful fifteen from
      twenty four primers inter simple sequences repeat markers. A dendrogram was
      constructed and shows distance values of the species between 12.1 and 53.5. The
      samples produced 63.96% polymorphic banding profiles. The genetic diversity (H')
      in this population was estimated using Shannon's index. The high H' value of
      0.501 reflected the somewhat wide range of distribution sites, which would adapt
      to environmental variations. Genetic evenness is 0.152. This value supports that
      all the studied samples have a small equal genetic abundance.

PMID- 19579939
TI  - Growth and inorganic solute accumulation of two barley varieties in salinity.
AB  - Salinity (NaCl stress) was applied with 50, 100, 200, 300 and 400 mM NaCl. The
      shoot and root length, fresh and dry weight, sodium and potassium content of two
      barley varieties (Hordeum vulgare L. var. Afzal and var. EMB82-12) were
      determined in various concentrations of NaCl. Root and shoot length, fresh and
      dry weight were decreased in two barley varieties in response to increased salt
      concentration, but the decrease was more significant in the root. Sodium content
      was increased and potassium content was decreased in two barley varieties in
      response to different salt regimes, but in general, these changes were more
      significant in the root.

PMID- 19579940
TI  - Impact of lead sub-chronic toxicity on recognition memory and motor activity of
      Wistar rat.
AB  - The aim of this research was to investigate the impact of lead nitrate
      administered in drinking water during 90 days (sub-chronic toxicity), on body
      weight gain, motor activity, brain lead accumulation and especially on
      recognition memory of Wistar rats. Two groups of young female Wistar rats were
      used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking
      water, while control rats received drinking water only, for 3 months. An
      evolution of body weight, motor activity, object recognition memory and measure
      of brain lead levels 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 (OF) test and to
      the Novel Object Recognizing (NOR) memory test. The results have shown a non
      significant effect in gain of body weight. However, a high significance was shown
      for horizontal activity (p<0.01), long memory term (p<0.01), at the end of
      testing period and for brain lead levels (p<0.05) between studied groups.

PMID- 19579941
TI  - Application of rye green manure in wheat rotation system alters soil water
      content and chemical characteristics under dryland condition in Maragheh.
AB  - This study was carried out with or without rye green manure along with 4 nitrogen
      fertilization treatments (0, 26, 103 and 337 (kg N ha(-1)) in 3 rotation system
      (green manure-wheat). Results showed that, although treatment effects on dryland
      wheat grain yield was not significant, but maximum grain yield (2484 kg ha(-1))
      was obtained from application of rye green manure along with 26 kg N ha(-1);
      which is 22% more than check (without rye green manure) treatment. Green manure
      application with or without nitrogen increased EC (dS m(-1)), but decreased OC, P
      (av.), Cu (av.), Mn (av.), Zn (av.) and sand in the soil. In contrast to green
      manure, application of nitrogen along with green manure increased saturation and
      clay. In the stage of stem appearance, soil moisture content decreased 8% in
      green-manure application but with nitrogen application the moisture increased 6%
      compared with check in 0-20 cm depth. It can be concluded that, green manure
      application is useful along with nitrogen fertilizer application in long term.
      This treatment could increase soil moisture content, which leads to higher wheat
      grain yield in dryland areas. In addition, green manure application could change
      some soil characteristics such as soil TNV%, which decreases availability of some
      essential nutrients for dryland wheat.

PMID- 19579942
TI  - Antibacterial effects of Iranian Mentha pulegium essential oil on isolates of
      Klebsiella sp.
AB  - The aim of the present study was the evaluation of the antibacterial activity of
      Mentha pulegium essential oil on isolates of Klebsiella. Thirty nine isolates
      were collected from urine specimens submitted to two educational hospitals in
      Urmia, Iran. The susceptibility of isolates was determined using a broth
      microdilution method. Minimum Inhibitory Concentration (MIC) and Minimum
      Bactericidal Concentration (MBC) of isolates to Mentha pulegium essential oil
      were determined. The susceptibilities of isolates to different antibiotics were
      tested using agar disk diffusion method. The rates of resistance were determined
      to antibiotics as follows: gentamicin 46.1%, tobramycin 48.7%, ceftizoxime 41%,
      co-trimoxazole 46.1%, amikacin 33.3%, cephtazidime 51.3%, ciprofloxacin 30.8%,
      kanamycin 53.8%, nalidixic acid 30.8% ampicillin 79.5% and nitrofurantoin 41%.
      Mentha pulegium essential oil possessed antibacterial effect against all isolates
      of Klebsiella sp. with MIC and MBC values in the range of 1.9 x 10(-3) to 4.9 x
      10(-4) mm3 mm(-3). In this study clinical isolates of Klebsiella sp. showed very
      high resistance to tested antibiotics. These results suggest the potential use of
      the Mentha pulegium essential oil for the control of multi-drug resistant
      Klebsiella sp. infections. However, more adequate toxicological study must be
      carried out to verify the possibility of using it for fighting microorganisms in
      human.

PMID- 19579943
TI  - Localized seborrhoeic dermatitis with hyperhidrosis due to mite infestation in an
      Iranian cross-breed ram.
AB  - A 3-years-old Iranian cross-breed ram with history of repeated local sweating,
      severe pruritus of body surface was referred to the veterinary clinic. On
      clinical examination wetness, warmness, pruritus and thickness of affected area
      were observed. In affected area, hair coat was staring and draggy. Body
      temperature, heart and respiratory rates were 40.4 degrees C, 120 beat min(-1)
      and 40 min(-1), respectively. Hematologic indices including packed cell volume,
      total and differential white blood cell (WBC) and total red blood cell (RBC) were
      normal. Laboratory examinations of skin scrapings confirmed infestation with
      Psoroptes ovis. Histopathologic findings included dilation of sweat glands,
      hyperplasia of sebaceous glands, hyperkeratosis, ulcer and scab formation and
      eosinophilic dermatitis. History and clinical findings association with the skin
      scraping and histopathologic findings indicated localized seborrhoeic dermatitis
      with hyperhidrosis. After treatment with ivermectin at the dose rate of 0.2 mg
      kg(-1), all clinical signs subsided. This confirmed that the cause of seborrhic
      dermatitis and hyperhidrosis was mite infestation and other possible causes were
      ruled out. So this is the first report of localized seborrhoeic dermatitis with
      hyperhidrosis due to mite infestation in animals.

PMID- 19579945
TI  - Investigation on effect of Populus alba stands distance on density of pests and
      their natural enemies population under poplar/alfalfa agroforestry system.
AB  - This study was carried out in order to distinguish the effect of agroforestry
      system (combination of agriculture and forestry) on pests and natural enemy's
      population in poplar research station. Wood is one of the first substances that
      naturally was used for a long period of time. Forage is an important production
      of natural resources too. Some factors such as proper lands deficit, lack of
      economy, pest and disease attacks and faced production of these materials with
      serious challenges. Agroforestry is a method for decrease of the mentioned
      problems. The stands of poplar had have planted by complete randomized design
      with 4 treatments (stand distance) of poplar/alfalfa include 3x4, 3x6.7, 3x8,
      3x10 m and 2 control treatments, alfalfa and poplar. The results showed that
      Chaitophorus populeti had the highest density in poplar and 3x10 m treatments.
      Monosteira unicostata is another insect pest that had most density in 3x10 m
      treatment. And alfalfa had high density of Chrysoperla carnea. The density of
      Coccinella septempunctata, were almost equal in all treatments.

PMID- 19579944
TI  - Detection of a histidine kinase mRNA in extraradical mycelium of Pisolithus
      tinctorius induced by the plant metabolites.
AB  - The aim of this study was to test the effect of acetosyringone (AS) on the
      accumulation of the histidine kinase coding mRNA, using in vitro propagated
      Pisolithus tinctorius. In the precontact phase of the ectomycorrhizal symbiosis,
      it is hypothesized that the plants releases chemicals, which are sensed by the
      fungal mycelium and in turn trigger the start of the symbiosis. The nature of
      such molecules is largely unknown; however, plant metabolite and their structural
      analogues have been widely used to induce infection in different microbe-plant
      interactions. A histidine kinase in Agrobacterium tumefaciens was activated by AS
      in the first step during the infection of dicotyledonous plants. A conserved gene
      fragment from the ectomycorrhizal fungus Pisolithus tinctorius was cloned using
      degenerate primers of conserved regions characteristic of the histidine kinase
      gene family. Then, the accumulation of this transcript in fungi incubated with AS
      was analyzed. RT-PCR and in situ hybridization suggest that this mRNA is
      synthesized in the presence of this plant analog in AS-treated mycelia. The
      findings presented here suggest a role of a histidine kinase involved in the
      early stages of ectomycorrhizal differentiation.

PMID- 19579946
TI  - Comparison of the effectiveness of weekly and daily iron supplementation in 6- to
      24-months-old babies in urban health centers of Sari, Iran.
AB  - The aim of this study was to compare the effectiveness of weekly and daily iron
      supplementation in 6 to 24 months infants. One-hundred Infants enrolled into this
      randomized controlled field trail. Fifteen drops was prescribed for the group who
      received daily supplementation of iron and 30 drops was prescribed for the group
      who was set up to receive weekly supplementation of iron. Hemoglobin and serum
      ferritin was measured after 12 weeks. After 12 weeks results showed that both
      weekly and daily supplementation significantly increased hemoglobin but for serum
      ferritin daily supplementation was only significant. However, there was no
      significant difference between two groups, so the weekly supplementation is
      recommended. According to the results and more tendencies to the weekly regimen,
      we recommended weekly regimen versus daily Iron supplementation.

PMID- 19579947
TI  - Priapism associated with olanzapine.
AB  - Priapism is a rare but serious adverse effect of psychotropic drugs where
      antipsychotic agents were implicated in 15 to 26% of priapism associated with
      medications. Among atypical antipsychotic, clozapine, risperidone and olanzapine
      have been reported to be associated with the condition. The patient was a 24
      years-old male referred to the OPD Clinic at Zare Psychiatry Hospital in 2007
      with symptoms of delusion of control, delusion of persecution, delusion of
      somatic and auditory hallucination, for the last year. He had priapism following
      the use of olanzapine. Serotonin-Dopamine Antagonist (SDA) should be proscribed
      with care became of this rare yet serious complication, especially in cases with
      previous history of priapism following the use of psychotropic drugs.

PMID- 19579948
TI  - Neuroprotective evaluation of extract of ginger (Zingiber officinale) root in
      monosodium glutamate-induced toxicity in different brain areas male albino rats.
AB  - In this study, the neuroprotective effect of the extract of ginger (Zingiber
      officinale) was investigated against MSG-induced neurotoxicity of male albino
      rat. The daily dose (4 mg kg(-1) b.wt.) i.p. injection of pure monosodium
      glutamate (MSG) for 30 days and subsequent withdrawal caused a significant
      decrease in epinephrine (E), norepinephrine (NE), dopamine (DA) and serotonin (5
      HT) content all tested areas (cerebellum, brainstem, striatum, cerebral cortex,
      hypothalamus and hippocampus) at most of the time intervals studied. This is may
      be due to activation of glutamate receptors, which led to increased the
      intracellular concentration of Ca(+2) ions, so the release of neurotransmitters
      is increased and the content of monoamines is decreased. After the withdrawal,
      the decrease in monoamines levels remained in striatum, cerebral cortex and
      hypothalamus, this may be due to the region specific effect of monosodium
      glutamate whereas, daily dose (100 mg kg(-1) b.wt.) i.p., injection of Ginger
      (Zingiber officinale) root extract for 30 days and subsequent withdrawal caused a
      significant increased in epinephrine (E), norepinephrine (NE), dopamine (DA) and
      serotonin (5-HT) content all tested areas at most of the time intervals studied.
      This is may be due to inhibition of 5HT-3-receptor effects at the same time the
      extract blockade of Ca(+2) channel, as result the release of neurotransmitter is
      decreased and the content is increased. After the extract withdrawal, the
      increase in monoamine levels remained in brainstem, striatum and hippocampus,
      this may be due to the region specific effect of the extract. The coadminisration
      of monosodium glutamate and ginger root extract caused increased in monoamine
      content in most of the tested brain areas at different time intervals. This is
      may be due to partly attributable to an antagonistic action of ginger root
      extracts on monosodium glutamate effect, so the monoamines content was increased.
      From these results, we can say that the ginger extract has a neuroprotective role
      against monosodium glutamate toxicity effect.

PMID- 19579949
TI  - Induce systemic resistance in lupine against root rot diseases.
AB  - Root rot caused by soil borne pathogenic fungi is the most sever disease attacks
      lupine plants. Isolation trials from diseased plants in some areas of Dakahlia
      Province (Egypt) was carried out. Rhizoctonia solani and Fusarium solani proved
      to be the most dominant isolates. Meanwhile, Fusarium oxysporum and Sclerotium
      rolfsii were less frequent. Efficacies of some plant resistance elicitors viz.:
      chitosan (CHI), Salicylic Acid (SA) and hydroquinone (HQ) in comparing to the
      fungicide Rhizolex T-50 as seed treatments showed significant reduction in the
      fungal growth in vitro. Chitosan at 8 g L(-1) and fungicide completely inhibited
      the growth of all isolated fungi, while SA at 1.4 g L(-1) and HQ at 1.2 g L(-1)
      inhibited the growth of Fusarium solani and F. oxysporum, respectively. The
      greenhouse experiments showed that S. rolfesii (No. 6) and R. solani (No. 2)
      followed by F. solani (No. 5) and F. oxysporum (No. 9) were the most aggressive
      root rot fungi. Soaking susceptible lupine seeds (Giza 1) in each one of the
      three selected elicitors showed a significant reduction in seedlings mortality.
      CHI at 8 g L(-1) was superior in increasing the percentage of healthy plants to
      record 72.5, 80.9, 62.7and 64.3%, when seeds were grown in soil infested with of
      F. solani, F. oxysporum, R. solani and S. rolfesii, respectively. These results
      were confirmed under field conditions in two different locations i.e., Tag El-Ezz
      and El-Serow Research Stations. CHI 8 g L(-1) proved to be the best elicitor
      after fungicide, in reducing lupine root rot disease. It showed 41 and 60%
      reduction in the plants mortality comparing to 56.37 and 69.13% in case of
      Rhizolex-T in Tag El-Ezz and El-Serow locations, respectively. The treatments
      were accompanied with a significant increase in lupine growth parameters, yield
      components and physiological aspects. Application of CHI at 8 g L(-1) or HQ at
      1.2 g L(-1) was the most potent in this respect as compared to check treatment.

PMID- 19579950
TI  - Describing variation in carcass quality traits of crossbred cattle.
AB  - In order to investigate variation in carcass quality traits, during a four-year
      period, mature Hereford cows (637) were mated to 97 sires from seven breeds
      (Jersey, Wagyu, Angus, Hereford, South Devon, Limousin and Belgian Blue),
      resulting in 1144 calves. Carcass production traits (carcass weight = HCWt, fat
      depth = P8, eye muscle area = EMA, intramuscular fat = IMF) were obtained from
      these cattle that constitute the Australia's Southern Crossbreeding Project. Data
      were analysed using multi-variate sire model containing fixed effects of sex,
      sire breed, slaughter age nested within sexes. Random effects were sire, dam,
      management (location-year-post-weaning groups) and environmental effects. HCWt of
      South Devon, Belgian Blue, Limousin and unexpectedly, Angus were the heaviest on
      the average. Hereford calves were intermediate and Jersey and Wagyu were lighter
      on the average than others. Carcasses of the Belgian Blue and Limousin had low P8
      and IMF, carcasses of Hereford and South Devon were intermediate and Angus,
      Jersey and Wagyu had high P8 and IMF. Management group effects were greatest
      especially for EMA and IMF. The sire variation was about 6, 6, 4 and 2% of total
      variation for HCWt, P8, EMA and IMF. Heritability ranged from 0.20 to 0.37
      (carcass weight). The genetic correlation between the two fat depots was not as
      high (0.18) as expected. Results from this study suggest that strategies to
      increase genetic potential for HCWt would increase the genetic potential for EMA
      but may reduce marbling and tend to slightly increase P8. All phenotypic
      correlations were positive, although not large.

PMID- 19579951
TI  - Variation of Ca, Sr, Ba and Mg in the otolith of mudskipper in west coast of
      Peninsular Malaysia.
AB  - A study on elemental composition in the otolith of giant mudskipper,
      Periophthalmodon schlosseri, was done from June to October 2003. Specimens were
      obtained from the mangrove areas of Kuala Selangor, Sepang and Melaka in the west
      coast of Peninsular Malaysia. A total of 70 sagitta otoliths were analyzed to
      detect variation of Sr, Ba and Mg, replacing the natural chemical composition of
      the otolith, which is the calcium carbonate (CaCO3). The average ratio of Sr:Ca
      was 0.11 x 10(-4), Ba:Ca was 5.7 x 10(-3) and Mg:Ca was 0.2 x 10(-3). Strong
      correlation (R > 0.8) between fish body size and otolith weight ofmudskipper (p <
      0.01) also found during this study.

PMID- 19579952
TI  - The effect of different concentrations of glycerol and DMSO on viability of
      Markhoz goat spermatozoa during different freezing temperatures steps.
AB  - The present study was conducted to determine the following; (1) the influence of
      different concentrations of glycerol (1, 3, 5 or 7%, v/v) in experiment 1 and
      DMSO (1, 1.25, 1.5 or 1.75% v/v) in experiment 2 added either at 37 or 5 degrees
      C and (2) the comparing of best concentration of glycerol with the best of DMSO,
      obtained in this study, on post-thaw motility, progressive motility, viability
      and normal acrosome of Markhoz goat sperm. In experiment 1, motility, progressive
      motility and viability of sperm were improved significantly (p < 0.05) by
      increasing of glycerol concentrations in the extenders, with the best results
      obtained with glycerol at 7% added at 37 degrees C. However, the rate of normal
      acrosome showed an opposite trend, i.e., the extender containing 1% glycerol
      added at 5 degrees C showed better results (p < 0.05). In experiment 2, the
      observed results showed similar tendencies to experiment 1. The data showed that
      the extender containing 1.75% DMSO concentration (the highest level) added at 37
      degrees C was significantly (p < 0.05) better than others. The percentage of
      intact acrosomes decreased significantly (p < 0.05) by increasing of DMSO
      concentrations, when added at 37 degrees C. Further, the results of 1% DMSO added
      at 5 degrees C was (p < 0.05) better than other groups. In regard to all
      evaluated parameters, the observed results in experiment 3 showed that extender
      containing 7% glycerol added at 37 degrees C was significantly (p < 0.05) better
      than 7% glycerol added at 5 degrees C and extender containing 1.75% DMSO added at
      both temperatures. In conclusion, the results of presented study indicated that
      glycerol is still the cryoprotectant of choice for freezing of Markhoz goat
      sperm.

PMID- 19579953
TI  - Sugar regulation of plastid reversion in citrus epicarp is mediated through
      organic acid metabolism.
AB  - The inhibition by sucrose of chromoplast reversion to chloroplast in citrus
      epicarp was studied by observing the effects of several sugars, sugar metabolites
      and 1-iodoacetate on chlorophyll reaccumulation in cultured Citrus paradisi Macf.
      pericarp segments. Pericarp segments of 1 cm in diameter were cut from yellow
      fruits and cultured on modified medium plus the indicated metabolites and kept
      under continuous fluorescent light. Accumulation of chlorophyll in the segments
      was measured with a spectrophotometer fitted with sphere reflectometer.
      Respiration was determined via., an infrared gas analyzer. Inhibition of
      regreening was not specific to a particular sugar. The organic acids malate,
      citrate, succinate, 2-oxoglutarate and especially malonate elicited effects
      similar to sucrose, but at much lower concentrations. However, malonate
      inhibition of chlorophyll accumulation was overcome by increased concentrations
      of glutamine. At concentrations that usually inhibited chlorophyll, malonate did
      not reduce CO2 production in the presence of glutamine or KNO3. Sucrose effects
      on regreening were reduced by 1-iodoacetate. These results indicate that sugar
      regulation of plastid reversion during regreening in citrus epicarp is not
      directly due to sugars, but is instead mediated through metabolism of sugars to
      organic acids, especially malonic acid.

PMID- 19579954
TI  - The impact of blood glucose and cholesterol levels on the manifestation of
      psychiatric disorders.
AB  - This study examined possible association of fasting glucose and lipid
      abnormalities in psychiatric patients on conventional antipsychotic medications.
      A total of 305 subjects were used for the study, comprising 203 clinically
      diagnosed psychiatric patients and 102 non-psychiatric subjects used as control
      at the psychiatric clinic at Komfo Anokye Teaching Hospital (KATH).
      Questionnaires were administered, blood pressure and anthropometric measurements
      undertaken. Fasting blood samples were taken for glucose and total cholesterol.
      The patients included those treated with conventional antipsychotic agents. It
      was noted, that there were higher rates of diabetes (22.17%) and lipid
      abnormalities (42.43%) with lower rate of hypertension (5.91%) and obesity
      (5.91%) across the sample as compared to control. This finding suggests that the
      high prevalence of diabetes and lipid abnormalities, in a young, psychiatrically
      ill population makes the case for aggressive screening.

PMID- 19579955
TI  - Aetiology of acute gastro-enteritis in children at Saint Camille Medical Centre,
      Ouagadougou, Burkina Faso.
AB  - The present study aims at identifying the infectious agents responsible for child
      Acute GastroEnteritis (AGE) in Ouagadougou. From May 5 2006 to June 22 2008, 648
      children aged from 2 to 41 months, with at least an average of 3 loose stools per
      day have been enrolled for coproculture, parasitology and virology test. Among
      them, 34 (5.25%) were HIV seropositive. A single sample of faeces from each child
      was used to identify enteropathogens. An infectious aetiology was identified in
      41.20% of cases. The pathogenic agents detected as responsible for the AGE are:
      Rotavirus 21.1%; Adenovirus 1.9%; Giardia 7.6% Entamoeba; 1.08%; entero
      pathogenic E. coli 41.7%; Salmonella 3.40%; Shigella 1.85% and Yersinia 1.70%.
      CONCLUSION: Therefore, these AGE etiologic agents constitute a problem of public
      health in Burkina Faso. Their control for the child would require: (1) a regular
      paediatric and clinical follow up; (2) health education of the population for
      food hygiene and (3) in case of absence of HIV infection in the mother, a
      promotion of exclusive breast-feeding up to the age of 4 months.

PMID- 19579956
TI  - Antioxidant and antibacterial activities of Combretum nioroense Aubrev. ex Keay
      (Combretaceae).
AB  - In this study, the antioxidant and antibacterial activities of acetone extract,
      ethyl acetate, n-butanol and n-hexane fractions of acetone extract from leaves of
      Combretum nioroense Aubrev. ex Keay were investigated. The total phenolics and
      total flavonoids contents in the fractions and acetone extract were determined by
      spectrophotometric methods using Folin-Ciocalteu and AlCl3, respectively. Two
      methods were adopted to assess the antioxidant activities: the Ferric Reducing
      Antioxidant Power (FRAP) and the radical scavenging activity of 2, 2'-azinobis (3
      ethylbenzothiozoline-6-sulfonate) radical cation (ABTS). The Minimum Inhibitory
      Concentrations (MICs) of the extract and fractions against pathogenic bacteria
      (4) and serotyped bacteria (4) from American Type Culture Collection (ATCC) were
      also determined using the agar-well diffusion method. The results showed that the
      butanol fraction, with the highest phenolic content, exhibited the best
      antioxidant and antibacterial activities as compared to the ethyl acetate
      fraction which contains more flavonoids.

PMID- 19579957
TI  - Molecular analysis of utility of a retrotransposon, p-SINE1-r2 in the Asian wild
      rice and weedy rice populations.
AB  - The distribution of a retrotransposon, p-SINE1-r2 located at the waxy locus was
      analyzed by the PCR assay in the perennial wild rice (Oryza rufipogon) which
      inhabited in four isolated and six disturbed populations and in the weedy rice
      population. The level of clonality of the wild rice species was determined in
      populations subject to level of water supply and another disturbance. The results
      showed that all four isolated populations carried the genotype (-/-) and (-/+),
      while three genotypes (-/-), (-/+) and (+/+) was found on the six populations
      which grown near by rice fields. This finding was strongly supported the idea
      that the original wild rice populations of O. rufipogon exhibited prominent
      genotype (-/-) and (-/+) and mainly propagated by vegetative reproduction and the
      allele (+) which found in the wild rice plant with the genotype (+/+) may
      originated from gene flow from cultivated rice to wild rice. Weedy rice
      accessions used in this study showed the three genotypes based on this DNA locus.
      The distribution of this DNA locus in wild rice and weedy rice populations were
      deviated from the Hardy-Weinberg equilibrium. The perennial wild rice populations
      were annually under season drought (March to May of the year in Thailand, Laos
      and Cambodia), they tended to have small size clones with relatively high clonal
      diversity (i.e., number of genotypes), except for the population from Cambodia,
      which carried only the genotype (-/+). Although DNA maker used to detect genetic
      variation at population levels is too small, but this locus is very sensitive
      enough to be a useful indicator for genetic variation at the population level.

PMID- 19579958
TI  - Oxygen saturation improvement after adenotonsillectomy in children.
AB  - The goal of this study was to establish whether adenotonsillectomy is effective
      on the severity of oxygen desaturation or improve oxygen saturation in children
      with sleep breathing disorders. Thirty-two children, aged 4-7 years, with
      clinical indication for adenotonsillectomy were enrolled in a non-controlled
      clinical trial. Pre- and postoperative nocturnal oxygen saturation monitoring was
      done and oxygen desaturation index as well as desaturation events were analyzed
      using Wilcoxon and paired Student's t-tests. Snoring was the most prevalent
      (87.5%) complaint before operation. The study revealed a significant improvement
      in the postoperative oxygen desaturation index (1.60 +/- 3.22) compared with the
      preoperative oxygen desaturation index (3.98 +/- 4.93) (p < 0.01). Oxygen
      desaturation events at the level of oxygen saturation 85-89% was significantly
      improved after operation (p < 0.01). No significant differences were seen in the
      desaturation events at the levels of oxygen saturation lower than 85%. Nocturnal
      oxygen saturation improves mildly after adenotonsillectomy in children with sleep
      breathing disorders.

PMID- 19579959
TI  - Identification of Panulirus homarus puerulus larvae by restriction fragment
      length polymorphism of mitochondrial cytochrome oxidase I gene.
AB  - Molecular identification of puerulus larvae of Panulirus homarus of the genus
      Panulirus from Indian coast was studied by employing Polymerase Chain Reaction,
      Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the mitochondrial
      DNA (mtDNA) Cytochrome Oxidase Gene (COI) by agarose gel electrophoresis and
      Denaturing Gradient Gel Electrophoresis (DGGE). The size of amplified fragment of
      COI gene was estimated to be approximately 1300 base pairs (bp). Single fragment
      amplification was recorded during different stages of the life cycle. The RFLP
      digestion was carried out using five different restriction enzymes (BsplI, HhaI,
      RsaI, TaqI and AluI). The RFLP profile of the different endonucleases, varied
      between 1-5 restriction types. RFLP analysis using endonuclease TaqI enabled
      identification of P. homarus during different stages of its life history.

PMID- 19579960
TI  - Some morphological structural studies of cucurbitaceous tendrils under arid
      conditions.
AB  - This study was carried out at Khulis, Khulis Governorate, Makkah region, on the
      first of April during the growing season of 2007, to study the morphology and
      anatomy of tendrils in different eight of cucurbit genera. The results showed a
      great variation among the most tested cucurbit genera concerning the twisting,
      branching, number of tendrils per node and presence of tendril trunk. Also, shape
      of transverse sections were ovate, sinuate-rhombic, sinuate-emarginate oblong,
      emarginate-ovate, spherical, notched-ovate and reniform. Furthermore, presence of
      collenchymatous, sclerenchymatous tissues, number of vascular bundles in
      Transverse Section (TV) and arrangement of vascular bundles varied according to
      the studied species. It could be conclude from this research that there are a
      numerous of qualitative traits of tendrils which plays an important role in
      identification of cucrbitaceous plants for examples; the twisting, branching,
      transverse section shape, collenchymatous tissue, scleranchymatous tissue,
      tylosis and arrangement of vascular bundles.

PMID- 19579961
TI  - Dietary betaine affect duodenal histology of broilers challenged with a mixed
      coccidial infection.
AB  - The purpose of this research was to investigate effect of dietary betaine on
      intestinal morphology after an experimental coccidiosis. Hence a total of 189
      male and female broiler chicks were randomly assigned to 9 floor cages. Chicks
      were fed a basal diet supplemented with 0, 0.6 or 1.2 g kg(-1) betaine. All birds
      were inoculated orally with Eimeria oocysts on day 28. Duodenal morphology
      parameters and lesions were scored by microscopic observation on intestine
      samples which were taken at day 42 of age. Adding 1.2 g kg(-1) betaine to diet
      diminished intestinal lesions (p < 0.05). Dietary supplementation with 0.6 or 1.2
      g kg(-1) betaine significantly (p < 0.01) increased intraepithelial lymphocytes
      as well. Level of additive betaine had no effect on the ratio of villus
      height/crypt depth or villus surface area. Lamina propria of duodenum became
      thicker in the intestine of chickens which received more supplemental betaine via
      their diet. In conclusion, since the number of intraepithelial lymphocytes and
      thickness of lamina propria represent the condition of gut immune response, it
      seems that dietary betaine may immunomodulate the gastrointestinal tract of
      broilers. In addition, betaine effect on villus morphology measured later in life
      differed from what had been measured already earlier in life of the chicks.

PMID- 19579962
TI  - Length-weight relationship and spawning season of Sphyraena jello C., from
      Persian Gulf.
AB  - Length-weight relationship and spawning season of Pickhandle barracuda, Sphyraena
      jello (C.) were studied for one year in Boushehr waters of the Persian Gulf. In
      the present study, 311 specimens were collected during November 2006 to October
      2007. The samples composed of 151 (48.55%) male, 160 (51.45%) female; the sex
      ratio was M: F = 1 : 1.06. The b value ranged between 2.77 to 2.87 for male and
      female fishes, respectively. The relationship between body weight and length in
      total specimens was 2.82, indicating that this species show negative allometric
      growth. The peak spawning season of these fishes occur around spring, from April
      to June. The lowest Gonadosomatic Index recorded in August. The present study is
      the first record on length-weight relationship and spawning season of this
      species in the Persian Gulf region.

PMID- 19579963
TI  - Histological and electron microscopic studies of the effect of beta-carotene on
      the pancreas of streptozotocin (STZ)-induced diabetic rats.
AB  - To evaluate the protective effect of beta-carotene on induction of diabetes by
      streptozotocin (STZ), 45 albino rats, weighed about 110-130 g were used. They
      were divided randomly into six groups. GI rats used as control; GII rats were
      injected i.p. with a single dose of 40 mg streptozotocin (STZ) to become
      diabetic; GIII and GIV, the diabetic rats were injected i.p. with 0.3 and 0.1 mg
      beta-carotene, respectively; GV and GVI rats were injected i.p. only with 0.3 and
      0.1 mg beta-carotene respectively. At the end of the experiment, the final body
      weights, blood glucose and insulin levels were determined and the values were
      statistically analyzed. Histological, semithin and ultrathin sections were
      prepared for pancreatic tissues. In the diabetic rats (GII), there was
      significant loss in body weight accompanied by significant increase in blood
      glucose levels. In addition, many light and electron microscopic changes were
      observed in the acinar and endocrine beta-cells of islets of pancreas. These
      changes were summarized as disturbance of acini arrangement, shrinkage and
      pyknotic nuclei, vacuolation and dissolution of mitochondria and Golgi elements,
      degranulation of beta-cells. In addition to the significant decrease in blood
      glucose levels, 0.3 mg beta-carotene (Gill) had decreased most of these changes
      than 0.1 mg of it (GIV). So, GIII provides more protection for the pancreatic
      tissue more than GIV. Also, the results revealed that injection of rats only with
      0.3 and 0.1 mg beta-carotene (GV and GVI) had no observable changes in the
      pancreatic tissues, except that there was an increase in number of the vacuolized
      mitochondria in most acinar and beta-cells of islets. In conclusions, 0.3 mg beta
      carotene could normalize the biochemical disorders of diabetes and provides more
      protection for the pancreatic tissues than 0.1 mg from the damaging effect of STZ
      to a greater extent.

PMID- 19579964
TI  - Erosivity index of urban storms: case study of two stations of Kermanshah.
AB  - Present research examine the erosivity index of precipitation Kermanshah
      Province, two stations belonged to west Region Water Company named old Kermanshah
      and new Kermanshah were used, the duration of statistical period being 13 and 19
      years. Data on stations was prepared graphically and the extraction of storms was
      performed visually with 15 min temporal step. After descriptive data on storm was
      adjusted and arranged tabularly, their kinetic energies were calculated with
      Wischmier and Smith formula considering maximum intensity of 30 min. Next, they
      were placed in continuous 1-72 h rainfall groups. Resulting conclusions indicated
      that about 85% of storm were in 1-6 h continuations and 6 h continuations had the
      highest values of kinetic energy as well as of erosion index (R), but remained in
      very low erosion class; and old and new Kermanshah stations were placed in very
      low erosion class, with annual average of erosion index less than 500 MJ mm ha(
      1) h(-1).

PMID- 19579965
TI  - Kinetics of gene expression during exposure of mouse stem cells to activin A.
AB  - This study aimed to evaluate the pattern of gene expression induced by activin A
      in mouse Embryonic Stem Cells (ESCs). Mouse ES cells cultured in undifferentiated
      state by leukemia inhibitory factor and feeder layer cells. Following removing
      these two anti differentiation factors for 5 days and forming Embryoid Bodies
      (EBs), the cells divided to 8 equal cells per groups. Differentiation procedure
      was performed in a two staged protocol; Formed EBs for 4 days (Stage one);
      expanded differentiated ESCs on gelatin coated dishes for one week (stage two).
      In the stage one, the media of groups 2-7 contained 10, 30 and 100 ng mL(-1)
      Activin A. The media in stage two was the same for all groups and contained only
      Fetal Bovine Serum (FBS). The expression of undifferentiated, ectoderm, mesoderm
      and endoderm markers were compared with relative RT-PCR method and statistically
      analyzed. The expression of an undifferentiating marker; Nanog was increased in
      the Activin A treated groups of stage one. The expression of OCT4 reduced in
      Activin A treated groups in stage two. In the stage one, the expression of Nodal
      increased by Activin A. expression of sonic hedgehog (Shh) was suppressed in
      Activin A treated groups of both stages. In stage two, there were significant
      decrease for the expression of mesoderm (Brachyury) and Nodal and visceral
      endoderm (GATA4) markers (p < 0.01). The expression of definitive endoderm
      markers (PDX1, TAT) showed significantly increased in Activin A treated groups (p
      < 0.01). Activin A induced differentiation in high concentration by imbalance in
      undifferentiating markers. Nodal has a dual role, undifferentiating effect and
      regulation of visceral endoderm towards definitive endoderm. Overexpression of
      Nanog, alteration in the expression of Nodal and Shh inhibition are three
      mechanisms for explanation of differentiation induced by activin A in ES cells.
      These mechanisms induces cascade of gene expression that commits ESCs towards
      definitive endodermal cells.

PMID- 19579966
TI  - Serum lipid profile of breast cancer patients.
AB  - The purpose of this study was to carry out a comparative study to investigate the
      effect of lipid profile, oestradiol and obesity on the risk of a woman developing
      breast cancer. This study was carried out at the Komfo Anokye Teaching Hospital
      (KATH), Peace and Love Hospital, Oduom, Kumasi and Redeemed Clinic, Nima, Accra
      between May 2002 and March 2003. In this study, 200 consented women comprising
      100 breast cancer patients (43 pre- and 57 post-menopausal) and 100 controls (45
      pre- and 55 post-menopausal) with similar age range (25 to 80 years) were
      assessed for lipid profile, oestradiol and BMI. There was a significant increase
      in Body Mass Index (BMI) (p = 0.011), Total Cholesterol (TC) (p < 0.001),
      triglyceride (p = 0.026) and low density lipoprotein (LDL-cholesterol) (p =
      0.001) of the breast cancer patients compared to the controls. With the exception
      of oestradiol (EST) that decreased, the lipid profile generally increased with
      age in both subjects and controls with the subjects having a much higher value
      than the corresponding control. There was also a significant positive correlation
      between BMI and TC (r2 = 0.022; p = 0.002) and also between BMI and LDL
      cholesterol (r2 = 0.031; p = 0.0003). Apart from EST and LDL-cholesterol that
      were increased significantly only in the postmenopausal phase in comparison to
      the controls, BMI, TC and TG were increased in both pre-menopausal and post
      menopausal phases with HDL-cholesterol remaining unchanged. This study confirms
      the association between dyslipidaemia, BMI and increased breast cancer risk.

PMID- 19579967
TI  - The efficacy of disease modifying anti-rheumatic drugs in rheumatoid arthritis in
      local patients of Karachi.
AB  - The primary objective of the study is to assess the efficacy of the 'Disease
      Modifying AntiRheumatic Drugs (DMARDs) on the disease activity in Rheumatoid
      Arthritis (RA) in the local patients of Karachi. The secondary objective is to
      evaluate whether the combination of two concurrent DMARDs (Combination Therapy)
      is superior to a single DMARD (Mono-therapy). This is an open labeled
      retrospective case series. One hundred and five consecutive patients fulfilling
      1987 ACR criteria for the diagnosis of RA were initially selected from the case
      notes of out patients department. Sixty nine patients fulfilled the inclusion
      criteria and were finally recruited for analysis. Details of the Tender Joint
      Count (TJC), Swolen Joint Count (SJC), Patient Global Assessment (PGA) and ESR
      were obtained at six weeks, three months, six months and one year. Out of the 69
      patients studied 48 were in the mono-therapy group and 21 in the combination
      therapy group. Methotrexate (MTX) was the most commonly used single DMARD (75%)
      as well as the most frequent component of the combination groups (85%). The TJC,
      SJC and PGA analyses of all patients show that DMARDs are effective agents for
      clinically controlling RA activity. The speed of their beneficial effect is slow
      and unlike analgesics and NSAIDS, may take up to six weeks to start working. The
      6 week responses showed 32.49% improvement in TJC, 33.19% improvement in SJC and
      59% better responses in PGA. This response continued to show further improvement
      and at six months when TJC improved by 63.41%, SJC by 53.21% and PGA with 81%
      better responses. After 6 months the response reached a plateau but nevertheless
      maintained until 1 year with improvements in TJC by 66.23%, SJC by 56.48% and PGA
      with 88.23% better responses. The changes in ESR did not go parallel with the
      other three outcome measures. The mean baseline ESR of 56 reduced to 44 at 6
      weeks but rose again gradually to 54 at 1 year. The sub-group analysis did not
      show the overall superiority of combination therapy over mono-therapy. DMARDs are
      effective in controlling disease activity in RA. Their effect starts slowly over
      6 week and may take up to 6 months to show full benefits. The beneficial effect
      was maintained for at least 1 year. Sub-group analysis did not show any advantage
      of combination therapy over mono-therapy in this series of patients. Methotrexote
      being the most frequently used DMARDs in both groups and being most cost
      effective agent seems to be the most useful drug in RA in the developing world.

PMID- 19579968
TI  - Contributions to the moss flora of Gumushane Province (Torul and Kurtun
      districts, Turkey).
AB  - Some moss specimens were collected from Gumushane Province between September and
      October 2008. As a result of field and laboratory studies, 92 taxa belonging to
      22 families were identified. These taxa are presented in a list. All taxa are new
      to the study area (Gumushane Province). Eight taxa are (Ditrichum flexicaule
      (Schwaegr.) Hampe, Ditrichum pusillum (Hedw.) Hampe, Grimmia lisae De Not.,
      Grimmia montana Bruch and Schimp., Herzogiella seligeri (Brid.) Z. Iwats., Leskea
      polycarpa Hedw., Pohlia melanodon (Brid.) J. Shaw, Trichostomum tenuirostre (Hook
      and Taylor) Lindb. var. tenuirostre) new records for A4 Square (40-42 degrees N,
      38-42 degrees E) were determined. The aim of the study was to determine the moss
      taxa growing in Gumushane Province (Torul and Kurtun districts) and to make a
      contribution to the moss flora of Turkey.

PMID- 19579969
TI  - Effects of Brucella abortus biotype 1 infection on the reproductive performance
      of Sprague-Dawley rats.
AB  - The aim of this study was to assess the impact of Brucella abortus biotype 1
      infection on the reproductive performance using Sprague-Dawley (SD) rat model.
      Virgin female SD rats (n = 24) were infected intraperitoneally with 0.1 mL of
      saline containing 1 x 10(11) Colony Forming Unit (CFU) of pathogenic B. abortus
      biotype 1 Korean bovine isolate. Control rats (n = 24) were inoculated with 0.1
      mL of apyrogenic saline. Both inoculated and control rats were divided into six
      subgroups. Four rats in each subgroup were consistently bred at 3, 7, 14, 21, 28
      and 60 days after infection. B. abortus infection induced 41.67% infertility in
      the infected rats. The mean number of offspring/litter was 8.71 +/- 2.01 for
      infected rats and 12.87 +/- 1.42 for control rats (p < 0.001). The mean weight of
      the viable offspring was 6.10 +/- 0.36 g for infected rats and 7.15 +/- 0.40 g
      for control rats (p < 0.001). The rate of stillbirth was 12.30% in the infected
      rats. B. abortus biotype 1 was isolated from the uteri of the infected rats. The
      data of this study indicate that B. abortus biotype 1 infections in SD rat model
      affect reproduction adversely by causing infertility, stillbirth and loss of
      number and weight of offspring.

PMID- 19579970
TI  - An immunohistochemical study of beta1 integrin molecules (VLA-4, VLA-5, VLA-6) in
      all endometrial compartments of fertile and infertile women in Ahwaz-Iran.
AB  - In some cases of infertility, implantation failure is due to a lack of expression
      of specific critical participating proteins such as cell adhesion molecules. The
      expression of beta 1 (beta1) integrin molecules within endometrial tissue has
      been proposed as a marker of uterine receptivity during the implantation window.
      Present study was conducted to assess uterine receptivity in women with
      unexplained infertility using beta1 integrin molecules within endometrial tissue
      in comparison with fertile women. This retrospective study was performed using a
      semiquantitative analysis on the immunohistochemical staining of beta1 integrins
      (VLA-4, VLA-5, VLA-6) in the mid-secretory phase of endometrium. Specimens were
      obtained from 30 fertile women and 28 infertile patients with a history of
      unexplained infertility. Chi-Square test was used to compare the expression and
      defect of beta1 integrin molecules between two groups. The results showed beta1
      integrin molecules were present in fertile and infertile endometrial uterine
      tissues with different reactivity in different compartments. VLA-5 and VLA-6
      expression on endometrial compartments showed an unrelated pattern of staining in
      either fertile or infertile women. The majority of glandular epithelial cells and
      stromal cells expressed VLA-4 integrin molecules in fertile endometrium. However,
      the reactivity with VLA-4 reduced significantly in both glandular epithelial
      cells and stromal cells in infertile women (p = 0.001). In conclusion differences
      may explain causes of unexplained infertility and suggests that VLA-4 integrin
      molecule may contribute in uterine endometrial receptivity at the time of the
      implantation window which requires more investigations in benign gynecologic
      diseases.

PMID- 19579971
TI  - Iron bioavailability of rats fed liver, lentil, spinach and their mixtures.
AB  - To study the effects of dietary iron source (basal diet-FeSO4 x 7H2O, liver,
      lentil, spinach, liver + lentil, liver+spinach and lentil+spinach) on iron
      bioavailability, fifty-six Albino Sprague Dawley derived male 21 days old rats
      were fed on iron-deficient diet (7.8 mg Fe kg(-1) diet) and the mentioned seven
      iron containing diets (40 mg Fe kg(-1) diet) for 10 days. Rats fed liver diet
      showed higher iron apparent absorption (52.1%), hemoglobin (Hb) gain (0.94 g/100
      mL), Hb-iron gain (1.2 mg), Hb-regeneration efficiency (HRE%) (50.8%), relative
      efficiency of HRE% (106.5%), packed cell volume gain (2.22%) and mean corpuscular
      hemoglobin concentration (0.64 g dL(-1)). Liver resulted in an increase in these
      parameters when mixed with lentil and spinach diets. However, rats fed iron free
      diet showed the higher dry matter absorption.

PMID- 19579972
TI  - PCR and Elisa methods (IgG and IgM): their comparison with conventional
      techniques for diagnosis of Mycobacterium tuberculosis.
AB  - In order to establish a rapid and stable method for diagnosis of Mycobacterium
      tuberculosis infection and minimize the side effects of delayed diagnosis on
      patients and health system, a cross sectional study was carried out. Since, the
      infection rate with this bacteria increasing and one of the reasons for this
      increase is long process of laboratory identification, therefore establishing new
      diagnosis methods could decrease disease rate. To achieve this aim, collected
      sputum and blood specimens from 50 patients with clinical suspicion of pulmonary
      tuberculosis were studied with both traditional, acid-fast stain (AFB) and
      culture method compare to Enzyme-linked immunosorbent assay (Elisa) (IgG and IgM)
      and Polymerase Chain Reaction (PCR) methods. The sensitivity and specificity of
      all methods were determined by using the PCR results as the gold standard. The
      overall sensitivity, specificity, positive predictive value and negative
      predictive value of AFB were 17.64, 100, 100 and 70.12%. These values for culture
      method was 29.41, 100, 100 and 73.33% and for IgG antibody were 66.7, 81.81, 64.7
      and 81.81% and IgM antibody were 70.58, 90.9, 80 and 85.71%, respectively. It was
      concluded that maximum sensitivity and specificity can be achieved by PCR method.

PMID- 19579973
TI  - The effects of nitrogen starter fertilizer and plant density on yield, yield
      components and oil and protein content of soybean (Glycine max L. Merr).
AB  - Effects of nitrogen starter fertilizer and plant density on yield and oil and
      protein content of soybean (Glycine max L. Merr) are not well understood, because
      nitrogen starter fertilizer and plant density has been tested separately. Two
      years field experiment was conducted to evaluate effects of these factors on
      yield, yield components, oil and protein content in 2006 and 2007 in Kermanshah,
      Iran. The experiment was conducted on soybean (var. Williams) as a split-plot
      based on randomized complete blocks design with three replications. Nitrogen
      starter fertilizer treatments were arranged in three rates (0, 40, 80 kg ha(-1))
      as main plots and plant density as sub plots arranged with three levels (15, 30,
      45 plant m(-2)). Based on similarity treatments and experimental designs, the
      results of analysis of combined variance and mean comparisons showed significant
      (528.4 kg ha(-1) yield increase as density increased from 30 to 45 plant m(-2)
      and nitrogen starter fertilizer increased from 0 to 40 kg ha(-1) in two years.
      Analysis of correlation showed a positive significant correlation between yield
      and number of seed per plant (r = 0.724), number of pods and yield (r = 0.463),
      thousand seed weight and yield (r = 0.437). A linear regression was found between
      yield and number of seed per plant, number of pods and thousand seed weight
      (yield = 37.58 + 0.73x1-0.14x2 + 0.7x3; r2 = 0.56); p < 0.01). Seed protein was
      unaffected by plant densities, but nitrogen application changed it. Dissimilarly,
      oil content has a diverse respond to treatments. This experiment showed density
      of 45 plant m(-2) and application of nitrogen starter fertilizer 40 kg ha(-1) are
      optimum and increase grain yield under condition of our experiment. We suggest to
      conduct some experiments for understanding of linear relationship for number of
      pod for understanding of linear relationship for number of pod for levels of
      nitrogen starter and quadratic relationship for number of seed for levels of
      density.

PMID- 19579974
TI  - Cytological and toxicological properties of a decoction used for managing tumors
      in Southwestern Nigeria.
AB  - The cytological and toxicological potentials of an ethanol extract of a decoction
      used in South Western Nigeria for the management of breast tumors were evaluated
      using mice and Allium cepa models. The oral administration of the extract to the
      mice within the range of 400-1600 mg kg(-1) b. wt., dosage did not result in any
      mortality until 2000 mg kg(-1) body weight (b. wt.), when 60% mortality occurred.
      The LD50 of the extract administered intraperitoneally, was 400 mg kg(-1) b. wt.
      Furthermore, the extract induced macroscopic and microscopic changes causing a
      dose-related root growth inhibition and chromosomal aberrations in Allium cepa.
      The effect of the extract was more pronounced at 1600 mg kg((-1), dose while the
      EC50 was at 380 mg after 72 h. This decoction may present cytological and
      toxicological potential for managing breast tumors and corroborates its use in
      ethno medicine.

PMID- 19579975
TI  - Study on the effect of sulphur, glucose, nitrogen and plant residues on the
      immobilization of sulphate-S in soil.
AB  - In order to evaluate the relationship between sulphur (S), glucose (G), nitrogen
      (N) and plant residues (st), on sulphur immobilization and microbial
      transformation. Five soil samples from 0-30 cm of Bastam farmer's fields of
      Shahrood area were collected. Eleven treatments with different levels of S, G, N
      and plant residues (wheat straw) were applied in a randomized block design with
      three replications and incubated over 20, 45 and 60 days. The immobilization of
      SO4(-2)-S presented as a percentage of that added, was inversely related to its
      addition rate. Additions of glucose and plant residues increased with the C-to-S
      ratio of the added amendments, irrespective of their origins (glucose and plant
      residues). In the presence of C sources (glucose or plant residues). N
      significantly increased the immobilization of SO4(-2)-S, whilst the effect of N
      was insignificant in the absence of a C amendment. In first few days the amounts
      of added SO4(-2)-S immobilized were linearly correlated with the amounts of added
      S recovered in the soil microbial biomass. With further incubation the
      proportions of immobilized SO4(-2)-S remaining as biomass-S decreased. Decrease
      in biomass-S was thought to be due to the conversion ofbiomass-S into soil
      organic-S. Glucose addition increased the immobilization (microbial utilization
      and incorporation into the soil organic matter) of native soil SO4(-2)-S.
      However, N addition enhance the mineralization of soil organic-S, increasing the
      concentration of SO4(-2)-S in soil and the extent to which available-S can be
      immobilized is determined by both the amount of available-S and the availability
      of an utilizable C source.

PMID- 19579976
TI  - Procalcitonin role in differential diagnosis of infection stages and non
      infection inflammation.
AB  - The aim of this study is evaluation of procalcitonin role in the diagnosis of
      infectious and non infectious inflammation. This cross-sectional study was
      conducted in one hundred patients in Baqiyatallah Hospital of Iran in 2008.
      Patients suspected to infection were recruited to study. They were divided to
      four groups as: systemic inflammatory response syndrome, sepsis, sepsis syndrome
      and septic shock. Procalcitonin quantitative was assayed by immunoluminometric
      kit manufactured in Germany. Procalcitonin level was divided to four groups in <
      0.5 ng mL(-1) compatible for SIRS, 0.5-2 ng mL(-1) for sepsis and 2-10 ng mL(-1)
      for sepsis syndrome and > 10 ng mL(-1) for septic shock. Data was analyzed by
      SPSS 13 for window software; T student test, ANOVA and Chi-square were used. In
      this study 53(53%) of subjects were men with mean age of 56.16 +/- 19.5 years
      old. The diagnosis was SIRS in 36%, sepsis in 38%, sepsis syndrome in 14% and
      septic shock in 12% of cases. Procalcitonin level was less than 0.5 ng mL(-1) in
      61% and more than 10 ng mL(-1) in 10% of patients. Procalcitonin level showed
      significant association with septic shock, positive blood culture and mental
      dysfunction. Ultimately this study showed that high level of procalcitonin can
      differentiate septic shock from SIRS and other stages of infection. Dysfunction
      of mental status and high level of procalcitonin can determine septic shock.

PMID- 19579977
TI  - Circulation free leptin in diabetic patients and its correlation to insulin
      level.
AB  - Present researchers studied the relation between insulin with free and total
      leptin in type 2 diabetic patients. Thirty non insulin dependent diabetic obese
      patients (age: 50 +/- 12 year and BMI>30 kg m(-2)) and thirty non insulin
      dependent diabetic non obese patients (age: 49 +/- 25 year and BMI<25 kg m(-2))
      were studied. Free leptin was purified by Gel filtration Chromatography and the
      fractions were collected and then their free leptin was measured by a high
      sensitive ELISA Kit. Circulation total leptin and insulin were measured by ELISA.
      Circulation free and total leptin were significantly correlated to insulin (p <
      0.005). Free leptin concentrations were higher in women than in men (p < 0.001).
      Ratio of free leptin to total in obese subjects is more than non-obese subjects
      (0.27 +/- 0.1 vs. 0.03 +/- 0.04, p < 0.001). Ratio of free to total leptin showed
      a positive correlations with insulin (r = 0.58, p < 0.001) insulin resistance (r
      = 31, p < 0.015) and BMI (r = 0.86, p < 0.001). The majority of leptin which
      circulates in obese individuals was free form. Presumably it is bioactive portion
      of hormone and thus obese subjects are resistant to free leptin. These
      observations are consistent with the view that free leptin levels in diabetes
      patients attributed to changes in serum insulin level and insulin resistant.

PMID- 19579978
TI  - Evaluation of bateriologial and sanitary quality of drinking water stations and
      water tankers in Makkah Al-Mokarama.
AB  - The present study was conducted to evaluate the bacteriological and sanitary
      quality of drinking water produced in Makkah Al-Mokarama during the high season
      in the month of Ramadan. Water samples were collected both from the drinking
      water stations and the water tankers (in Arabic language called whitats) used to
      transport and distribute water in different places in the Holy city. Water
      samples were analyzed to determine the densities of HPC at 22 and 37 degrees C,
      total coliforms, E. coli and S. aureus. The bacteriological analysis of drinking
      water samples at 37 degrees C proved that 6.7-33.3, 20-46.7, 0-20 and 0-6.7% of
      total water samples contained HPC, total coliforms, E. coli and S. aureus,
      respectively which were higher than the safe limits for drinking water. The
      bacterial analysis of drinking water varied from one water station to another. On
      the other hand, drinking water transported by tankers appeared to be in the
      lowest category of water quality. Because out of total water samples 40-59%, 60
      68.8%, 31.2-37.5%, 10-25% contained HPC, total coliforms, E. coli and S. aureus,
      respectively, which were higher than the established safe limits of drinking
      water. One possible reason for poor quality of drinking water could be attributed
      to the application of inadequate water disinfection treatments and also the
      absence of sanitary aspects as supported by the bacteriological analysis which
      holds true especially for water supplied by tankers. In conclusion, it is
      important to apply proper water disinfection measures and provide sanitary
      monitoring programs during the production of drinking water as a whole and for
      the water tanker in particular.

PMID- 19579979
TI  - The effect of salinity on morphological characteristics of seven rice (Oryza
      sativa) genotypes differing in salt tolerance.
AB  - The effect of salinity on morphological characters of salt tolerant genotypes
      PVSB9, PVSB19, PNR381, PNR519, Iratom24 and salt sensitive genotype NS15 along
      with one standard check salt tolerant rice cultivar Pokkali were assessed in two
      factors Completely Randomized Design with four replications. Seven rice genotypes
      in combination with six levels of salinity (0, 3, 6, 9, 12 and 15 dS m(-1)) were
      randomly assigned in 168 experimental plastic pots. The different morphological
      characters studied include plant height, total number of tillers, Root Dry Weight
      (RDW), Shoot Dry Weight (SDW) and Total Dry Matter (TDM) content of the selected
      rice genotypes in view to evaluate their response at different salinity levels.
      The results on the effect of morphological characters indicated that plant
      height, total tillers, root, shoot and total dry matter were significantly
      decreased by the application of salinity. The genotypes Pokkali, PVSB9, PVSB19
      showed significantly higher values and the lowest value of all these characters
      were recorded in NS15. A sharp decrease in percent relative-plant height, RDW,
      SDW, TDM, total tillers were found in susceptible genotype NS 15 after 3 dS m(-1)
      level of salinity, but these characters were found to decrease slowly in tolerant
      genotypes.

PMID- 19579980
TI  - Antioxidant activity of Crataegus pentaegyna subsp. elburensis fruits extracts
      used in traditional medicine in Iran.
AB  - In this study, the antioxidant activity of methanol and aqueous extracts of
      Crataegus pentaegyna subsp. elburensis (CP) were examined by various in vitro
      assay systems, i.e., DPPH and nitric oxide radical scavenging, reducing power,
      linoleic acid and iron ion chelating power. IC50 for DPPH radical-scavenging
      activity was 341.29 +/- 1.29 for methanol and 269.31 +/- 2.11 microg mL(-1) for
      aqueous extract. Reducing powers of extracts also increased with the increase of
      their concentrations. Both extracts exhibited a weak reducing power at 25-800
      microg mL(-1). Extracts exhibited weak nitric oxide radical scavenging and Fe2+
      chelating ability. Methanol extract showed higher Fe2+ chelating ability (IC50 =
      1.84 +/- 0.01 mg mL(-1)). Both tested extracts exhibited high antioxidant
      activity. Extracts showed high total phenolic content.

PMID- 19579981
TI  - A comparative study between detached leaf and plastic growth pouches techniques
      on the infection of pseudocercospora leaf spot disease of cowpea cultivars (Vigna
      unguiculata L. Walp) in northeast Thailand.
AB  - This glasshouse experiment was carried out in the 2004 at the Department of
      Agricultural Production, Faculty of Technology, Mahasarakham University,
      Mahasarakham 4400, Northeast Thailand to compare amounts of infection of
      Pseudocercospora leaf spot disease in leaves of cowpea cultivars being screened
      between detached leaf and plastic growth pouches techniques. The experiment was
      laid in a factorial arranged in a Randomized Complete Block Design (RCBD) with
      four replications. KVC7, IT81D-1228-14-1 and KKU25 cowpea cultivars were used as
      factor A, detached leaf and plastic growth pouches techniques were used as factor
      B and four levels of the concentrations of the spores of the disease, i.e., 0, l
      x 10(4), 5 x 10(4) and 1 x 10(5) of disease forming units mL(-1) of distilled
      water were used as factor C. The results showed that KVC7 and IT81D-1228-14-1
      cultivars possessed immune and high resistant properties against the disease,
      respectively, whereas KKU25 cultivar ranked as a susceptible cultivar. Detached
      leaf technique gave higher amount of infection of the disease than plastic growth
      pouches technique and the differences were highly significant. A plentiful amount
      of Infected disease was attained with an inoculation rate of l x 10(5) forming
      units mL(-1) of distilled water, which was considered too high and the most
      appropriate concentrations for use lie on both concentrations, i.e., 1 x 10(4)
      and 5 x 10(4) forming units mL(-1) of distilled water. An interaction among
      factors AxBxC was severely found with KKU25 cultivar, particularly on day 28
      after inoculation, whilst other two cultivars gave a minute amount of disease
      incidences (%) where detached leaf technique gave much higher disease incidences
      than plastic growth pouches technique, thus detached leaf technique should be of
      higher advantages.

PMID- 19579982
TI  - Iron supplementation during pregnancy and birth weight in Iran: a retrospective
      study.
AB  - This study was designed to determine the relationship between Maternal Iron
      Supplement (MIS) and Birth Weight (BW) in a rural area in North of Iran. A sample
      size of 2881 children was chosen by cluster and random sampling from 20 villages.
      MIS status, BW and demographic characteristics were recorded. Data was analyzed
      by SPSS 15 software and statistical significance was defined as p < 0.05. Mean
      and SD of BW is 3177.2 +/- 522.6 g. Taking iron supplement by mothers with low
      birth weight, normal birth weight and high birth weight were shown 96.1, 94.9 and
      87.1%, respectively. MIS increased birth weight only,in younger mother, <5 family
      number and <3rd birth order but there is no statistical significant. Logistic
      regression showed that younger mother (p = 0.014, OR = 2.181), Low income (p =
      0.001, OR = 1.601) and primary birth order (p = 0.001, OR = 1.738) are risk
      factor for low birth weight. MIS only in younger mother, low economic status and
      primary birth order led to improve birth weight. Maternal age, economic status,
      birth order and ethnicity are risk factors for low birth weight.

PMID- 19579983
TI  - Combining ability and heterosis for some agronomic traits in crosses of maize.
AB  - In 2007, five maize inbred lines were crossed in all possible combinations
      without reciprocals by using a half diallel crosses mating design to obtain 10
      single cross. Inbred parents and their F1 single crosses were evaluated through
      2008 season to evaluate the role of general and specific combining ability and
      heterosis for some agronomic traits. Results indicated that mean squares of
      genotypes were highly significant for all studied traits, i.e., ear diameter, ear
      length, number of kernels/row, 100-kernel weight, ear yield per plant, grain
      yield per plant and shelling percentage. General Combining Ability (GCA) and
      Specific Combining Ability (SCA) mean squares were highly significant for all
      studied traits. The GCA/SCA ratio was less than unity for all studied traits;
      this means that these traits are predominantly controlled by non-additive gene
      action. Significant positive GCA effects were found for all studied traits. Based
      on GCA estimates, it could be concluded that the best combiners were Rg5 and Rg8
      inbred lines for most of studied traits. This result indicated that these inbred
      lines could be considered as good combiners for improving these traits.
      Significant positive SCA effects were found for all studied traits. Based on SCA
      effects, it could be concluded that the best crosses for ear diameter and 100
      kernels weigh was G507AxG516; for ear length was G516xRg8; for kernels number/row
      was G516xG278; for ear yield/plant, grain yield/plant and Shelling percentage was
      G278xRg5. These crosses could be selected and used in breeding programs for
      improving these traits. Results showed positive significant heterosis values for
      all studied traits. The best crosses over both their mid-parents and better
      parents for ear diameter and 100-kernel weigh was G507AxG516; for ear length and
      kernels number/row was G516xG278; for ear yield/plant and grain yield/plant was
      G278xRg8 and for Shelling percentage was G278xRg5.

PMID- 19579984
TI  - Clinical finding and outcome in suicidal attempt due to intravenous injection of
      kerosene.
AB  - The aim of this study was to describe the clinical findings and outcome in
      suicidal attempted due to intravenous injection of kerosene. This case series
      study was conducted in the Department of Internal Medicine, Shohada Ashayer
      Hospital, Khorramabad, Iran during 8 years. Ten IV drug addicts who intravenously
      injected themselves with Kerosene were collected. All patients admitted in ICU,
      completely monitored for cardiopulmonary status and consulted with pulmonologist,
      cardiologist, neurologist, anesthesiologist and dermatologist. Therapeutic
      decision including intubation, antibiotics therapy, and oxygen, correction of
      water and electrolyte disturbances was applied according patients condition. The
      data were analyzed with fisher-exact test. Nine (90%) patients were male, 1(10%)
      was female. All cases were attempted suicides and IV drug abusers. Mean age was
      20.3 +/- 2 years. The patients' mean arrival time to the hospital after poisoning
      was 1.1 h. Death of 5(50%) patients was related to the higher doses (>5 mL) of
      intravenous injection of kerosene, the most clinical findings were related to
      pulmonary involvement with pulmonary edema and subsequent cardiac and
      neurological complications and phlebitis due to IV injection. Intravenous
      kerosene injection causes major injury to the lungs, the organ bearing the first
      capillary bed encountered. Other complications including cardiac and neurological
      seems to be related to severe hypoxia and other metabolic disturbances due to
      lung injury. The amounts of kerosene were major determinants of lethality. Early
      and aggressive supportive care might be conducive to a favorable outcome with
      minimal residual pulmonary squeal at least in patients with injection of less
      than 5 mL of kerosene.

PMID- 19579985
TI  - Weight differences of male and female pupae of gypsy moth (Lymantria dispar) and
      host-sex preference by two parasitoid species Lymantrichneumon disparis and
      Exorista larvarum.
AB  - Weight differences of male and female pupae of gypsy moth [Lymantria dispar L.
      (Lepidoptera: Lymantriidae)] and its two parasitoids Lymantrichneumon disparis
      (Poda) (Hymenoptera: Ichneumonidae) and Exorista larvarum (L.) (Diptera:
      Tachinidae) host preference were examined in this study. Lymantria dispar pupae
      were collected from trunks and branches of 20 Ironwood trees (Parotia persica) in
      two sampling dates, 10 July 2005 and 24 July 2005. The pest pupae were weighted
      and then saved at room temperature until adults of gypsy moth or its parasitoids
      emerged. The most L. dispar pupae collected in the first sampling were male
      whereas those in the second one were female and both male and female pupae in the
      second sampling were smaller than those in first sampling. The majority of male
      pupae (98.29%) were less than 0.6 g and most of female pupae (79.39%) were more
      than 0.6 g in weight. The most of L. disparis emerged from male pupae of L.
      dispar, whereas the majority of E. larvarum emerged from female pupae.
      Implications of the results for biological control strategy of gypsy moth are
      discussed.

PMID- 19579986
TI  - Antioxidant activities of methanol extract of Sambucus ebulus L. flower.
AB  - In this study antioxidant activity of methanol extract of Sambucus ebulus L.
      flower was investigated employing various in vitro assay systems, i.e., DPPH and
      nitric oxide radical scavenging, hydrogen peroxide scavenging, reducing power,
      iron ion chelating power and linoleic acid. IC50 for DPPH radical-scavenging
      activity was 228 +/- 12 microg mL(-1). The extract showed very high activity in
      the reducing power assay that was comparable with positive control, vitamin C.
      The extract showed good nitric oxide-scavenging activity (IC50 = 309 +/- 14
      microg mL(-1). It was found that antioxidant activity was dose dependent i.e.,
      activity was increased with the increase of their concentrations. The extract
      showed very weak activity in iron ion chelating (IC50 = 1.3 +/- 0.07 mg mL(-1)).
      It is showed very good activity in scavenging of hydrogen'peroxide. IC50 for
      scavenging of extract was 59.5 +/- 3.3 mcirog mL(-1). The extracts exhibited no
      activity in linoleic acid model. The total phenolic content of flower was 56.3 +/
      2.81 mg gallic acid equivalent g(-1) of extract powder and total flavonoid
      content was 14.5 +/- 0.72 mg quercetin equivalent g(-1) of extract powder by
      reference to standard curve.

PMID- 19579988
TI  - The study of prevalence and antimicrobial susceptibility of tracheal bacterial
      strains isolated from pediatric patients.
AB  - The aim of this study was to investigate the prevalence and antimicrobial
      susceptibility of bacterial strains isolated from tracheal specimens obtained
      from pediatric patients admitted to a major children hospital in Tehran, in 2007.
      Tracheal specimens were cultured on the appropriate bacteriological media.
      Bacterial isolates were identified by standard biochemical and serological tests.
      Antimicrobial susceptibility testing was performed according to Clinical and
      Laboratory Standards Institute (CLSI) guidelines. Pseudomonas spp. was identified
      as the most prevalent bacterial isolate (32%) followed by Staphylococcus aureus
      (27.6%). Thirty strains (16%) were identified as Klebsiella spp., 18 (9.6%) as
      Enterobacter spp. and the rest belonged to coagolase negative Staphylococci,
      Streptococcus viridans, Acinetobacter spp., Escherichia coli and Neisseria spp.
      All Pseudomonas spp. were resistant to ampicllin, kanamycin and ceftizoxime.
      Staphylococcus and Klebsiella spp. showed high degree of resistance to 40% of
      examined antibiotics.

PMID- 19579987
TI  - Influence of metoprolol on systolic and diastolic function in children with heart
      failure.
AB  - The aim of this study was to assess the effect ofmetoprolol on cardiac function
      in children with heart failure. This randomized double-blind placebo controlled
      clinical trial was performed in children with heart failure due to left ventricle
      volume overload structural heart disease such as VSD, PDA, AI and MR who referred
      to pediatric cardiology clinics in sari in 2007. The patients divided into case
      and control groups. All cases were matched as viewpoints of age, sex, weight,
      kinds of primary disease and cardiac drugs (except for metoprolol).Metoprolol
      with single daily dose of 1 mg kg(-1) and placebo were given to patients in case
      and control groups respectively. Echocardiography with cardiac indices of
      systolic and diastolic function was done as baseline and monthly for 3 months in
      all the patients. Data were analyzed using SPSS software and statistical t-test.
      Thirty patients (16 cases and 14 controls) were enrolled in the study. CI, MPI
      and dv/dt (dt) decreased significantly at first month. Significant changes in
      LVEF and EPSS appeared on the second month and in E wave and E/A appeared on the
      third month. The results were in favor of systolic and diastolic improvement.
      Metoprolol causes improvement of cardiac systolic and diastolic function in
      children with heart failure due to cardiac defect. Therefore, metoprolol is
      recommended in patients with heart failure in above mentioned diseases that have
      not been controlled adequately in spite of receiving standard cardiac failure
      drug therapy such as an inotrope, a diuretic and a vasodilator agent.

PMID- 19579989
TI  - Partial characterization of the lectin of runner beans (Phaseolus coccieneus)
      var. Alubia.
AB  - We extracted and partial characterized lectin from runner beans (Phaseolus
      coccineus L.). This lectin shows a great affinity to fetuin-agarose column like
      others lectins and the electrophoretic gels point one band of approximately 45
      kDa. In addition to the previous assays, we detected the presence of lectins by
      agglutination assays. We know that lectins are non-enzymatic proteins or
      glycoproteins that bind carbohydrates. The biological function of plant lectins
      is not fully understood, but they are hypothesized to be involved in a number of
      intrinsic processes. Many of those processes include hemagglutination. We believe
      that the P. coocineus lectin will be an important tool for know the properties of
      many lectins, included their capacity to detected and quantify tumor markers.

PMID- 19579991
TI  - Medical treatment of lung collapse in children.
AB  - This study was aimed to establish non-invasive (medical) treatment of lung
      collapse for children who are admitted to PICU of Tabriz Children's Hospital.
      During a period of 48 months (from March 2004 to February 2008), an
      interventional pre-experimental study carried out on 90 children suffering from
      lung collapse who received non-invasive treatment; which mainly consists of
      postural drainage, chest physiotherapy and inhalation of aerosols (fluid as
      floating droplets in air) and bronchodilators. Eighty six out of 90 studied
      patients (94.5%) with the average age of 22 months, responded to this treatment
      within the average duration of 3.4 days, as collapsed area of lung reexpanded.
      Because of simplicity and easy availability of this method of treatment and also
      its efficacy and scientific base; it can substitute bronchoscopic treatment and
      its usage be generalized to small hospitals.

PMID- 19579990
TI  - Rapid detection of Borrelia burgdorferi strains by nested polymerase chain
      reaction.
AB  - This study was carried out to evaluate the nested PCR for specific detection of
      different strains of B. burgdorferi. Five strains of B. burgdorferi including ACA
      1, B-31, 2B45, 3B45, 7B49 obtained from different countries were used in this
      study. The strains of B. hermsii, Escherichia. coli and T. pallidum were also
      included as control strains. Two pairs of nested PCR primers were used to amplify
      the gene encoding the Osp-A protein of B. burgdorfer under standard PCR
      condition. In a two stage procedure, nested PCR yielded a positive reaction for
      five tested strains of B. burgdorferi. None the strains including B. hermsii, E.
      coli and T. pallidum showed positive reaction when used as control strains in
      PCR. In conclusion, nested PCR showed acceptable specificity for rapid detection
      ofB. burgdorferi.

PMID- 19579992
TI  - Survey of factors effective on re-intubation among children admitted to pediatric
      intensive care unit.
AB  - This study was aimed to recognize the risk factors of re intubation among
      children who were admitted to pediatric intensive care unit. in an analytical
      cross-sectional study, the risk factors of reintubation in two groups of patients
      compared, both groups consist of 55 children, one with successful extubation and
      another with extubation failure. The study showed that neuromuscular disorders
      are the main underlying disease in extubation-failure group (p = 0.004). Besides,
      in comparison between two group of patients who had successful versus failed
      extubation, hypercapnia (PaCO2 > 50 mmHg) was shown to be the most common cause
      of both the first intubation (p = 0.003) and reintubation (p = 0.002) in patients
      who failed extubation. This study shows that neuromuscular disorders as a
      background, are the most common causes which defeat weaning from ventilator or
      result in reintubation by induction of hypercapnia.

PMID- 19579993
TI  - A new index for discrimination between iron deficiency anemia and beta
      thalassemia minor: results in 284 patients.
AB  - The present study reports the results in 284 patients of applying a recently
      developed index, MCV-(10 x RBC), for discrimination between beta-thalassemia
      trait (beta-TT) and Iron Deficiency Anemia (IDA), the two most common causes of
      microcytic hypochromic anemias. A total of 284 carefully selected patients (130
      patients with IDA and 154 with beta-TT) were studied. Sensitivity, specificity
      and Youden's index were compared between the proposed index and four other
      indices, namely England-Fraser, Mentzer, Srivastava and RBC count. The new index
      correctly identified 263 (92.96%) patients, standing inferior only to Mentzer
      which correctly diagnosed 269 (94.71%) patients. The best discrimination index
      according to Youden's criteria was Mentzer (Youden's index = 90.1) followed by
      the new index (Youden's index = 85.5). There are remarkable inconsistencies among
      the results obtained in different studies. Larger studies are needed to establish
      the optimal discrimination index as well as to confirm the results obtained in
      the present study. Nevertheless, the epidemiological indices of the proposed
      discrimination index and the simplicity of its calculation make it acceptable for
      use in Iran.

PMID- 19579994
TI  - Transient facial nerve baroparesis: case report.
AB  - We present a rare case of facial paralysis that was unusual not only in its
      causation but also in its rapidity of onset and recovery. We describe a rare case
      history of this accruing in 35 years old women traveling at the high altitude
      mountain road referred to ENT clinic with sudden symptoms of middle ear effusion
      and facial nerve paralysis. Patient had undergone medical systemic steroid
      treatment and after 3-4 weeks she had a good recovery of facial palsy with a
      minimum remnant of sensory neural hearing loss. Facial nerve paralysis resulting
      from a barotrauma of the middle ear is suggested. The correct diagnosis of this
      condition is important and unnecessary treatment should be avoided.

PMID- 19579996
TI  - Heterosis in some crosses of bread wheat under irrigation and drought conditions.
AB  - Five bread wheat varieties with different characteristics were crossed in a half
      diallel model in 2005/2006 season. The five parents and their 10 F1 hybrids were
      evaluated under normal and water stress conditions during 2006/2007 season, to
      estimate heterosis of some wheat crosses for drought tolerance and selecting the
      crosses which could be useful in breeding programs for drought tolerance. The
      results indicated that, the best crosses over their mid parents at water stress
      condition for days to heading was Sakha-61 x Sakha-93; for flag leaf area were
      Giza-168 x Gemmeiza-9 and Sakha-61 x Gemmeiza-9 and for plant height was Sakha-61
      x Sakha-93. The best crosses over their mid parents at both normal and stress
      conditions for days to maturity was Sakha-61 x Gemmeiza-9; for flag leaf area
      were Giza-168 x Sakha-61, Sakha-8 x Gemmeiza-9 and Sakha-93 x Gemmeiza-9; for
      spikes/plant were Sakha-8 x Sakha-61, Sakha-8 x Gemmeiza-9 and Sakha-61 x Sakha
      93; for kernels/spike were Giza-168 x Sakha-8, Giza-168 x Sakha-61, Giza-168 x
      Sakha-93 and Sakha-8 x Gemmeiza-9; for 100-kernel weight were Giza-168 x Gemmeiza
      9, Sakha-61 x Sakha-93 and Sakha-93 x Gemmeiza-9 and for grain yield/plant were
      Giza-168 x Sakha-93, Sakha-8 x Gemmeiza-9 and Sakha-93 x Gemmeiza-9. The best
      crosses over their better parents at water stress condition for flag leaf area
      were Giza-168 x Sakha-8, Giza-168 x Gemmeiza-9 and Sakha-8 x Gemmeiza-9; for
      plant height were Giza-168 x Gemmeiza-9 and Sakha-8 x Sakha-61. The best crosses
      over better parents at both normal and stress conditions for plant height were
      Giza-168 x Sakha-8, Sakha-8 x Gemmeiza-9 and Sakha-93 x Gemmeiza-9; for
      spikes/plant were Sakha-8xSakha-61, Sakha-61 x Sakha-93 and Sakha-8 x Gemmeiza-9;
      forkernels/spike were Giza-168 x Sakha-61 and Giza-168 x Sakha-93 and for grain
      yield/plant were Sakha-61 x Sakha-93 and Sakha-93 x Gemmeiza-9. Estimation of
      useful heterosis over better parent for grain yield/plant proved that it never
      exceeds 10.16% at normal condition (cross Giza-168 x Gemmeiza-9) and 12.76% at
      stress condition (cross Sakha-93 x Gemmeiza-9). Useful segregate could be
      selected from such hybrids as hybrids wheat are still under experimentation in
      Egypt.

PMID- 19579995
TI  - Risk of mortality in pediatric intensive care unit, assessed by PRISM-III.
AB  - This study aimed at evaluating the mortality rate in a PICU applying PRISM-III.
      Two hundred and twenty one infants and children consecutively admitted to PICU of
      Tabriz Children's Hospital were studied during a 13 months period of time. Data
      required for calculating the PRISM-III score were collected during the first 24 h
      of PICU stay in all patients. The prediction of actual mortality by PRISM-III
      scoring was evaluated by the Hosmer and Lemeshow goodness-of-fit test. Receiver
      Operating Characteristic (ROC) curve was constructed, as well. The observed (O)
      short-term (during hospital stay) mortality rate was compared with the expected
      (E) figures as the O/E ratio. The mean value of the PRISM-III score was 14.22 +/-
      9.57(2-42). ROC analysis indicated a strong predictive power for the PRISM-III
      (area under the curve = 0.898) and the test was well fit to the designed study
      (goodness-of-fit p-value = 0.161). The observed short-term mortality rate was
      9.05% and the expected mortality rate by the PRISM-III scoring was 9% (O/E ratio
      = 1.005). The PRISM-III scoring system was highly calibrated in our institute.

PMID- 19579997
TI  - Investigation of some effective factors on yield traits of Pepino (Solanum
      muricatum) as a new vegetable in Iran.
AB  - To find out the effects of media culture and foliar fertilization on some yield
      traits including the number of fruits per bush, mean weight of fruit, yield of
      per bush, long of fruits and diameter of fruits 9 months completely randomized
      factorial experiment (3 x 5) with four replications was conducted. Media culture
      treatments include 5 levels namely soil; mixture of soil and vermy compost;
      mixture of soil and sand; mixture of soil and peat moss and mixture of soil, sand
      and peat moss. Foliar fertilization treatments include 3 levels namely applying
      once a week, once a 3 week and no fertilization (control). The results showed
      that the media culture treatments on the whole of traits and foliar fertilization
      also on the whole of traits except yield of per bush had a significant difference
      (p < 0.01). In the foliar fertilization except yield per bush the once a 3 week
      fertilization caused highest increase than other treatments and in the media
      culture treatments, the mixture of soil and peat moss showed highest increase
      than other treatments.

PMID- 19579998
TI  - Dose-dependent effects of endosulfan and malathion on adult Wistar albino rat
      ovaries.
AB  - In this study, histological effects and malondialdehyde (MDA) levels were
      investigated by endosulfan and malathion in adult female rat ovaries. An increase
      of MDA level in rat ovarium tissues due to endosulfan and malathion may be an
      indicator of the free radicals occurred during the metabolism and their lipid
      peroxidative inducing damage. In this study in accordance with the biochemical
      findings, the study demonstrated that there are pronounced structural defects in
      histological examinations of ovarian tissues in rats which were administered
      endosulfan and malathion. It has been observed that the size of ovarian tissues
      of rats which were administered endosulfan and malathion in different doses was
      decreased in various levels. There was a significant decrease healthy follicles
      and a significant increase atretic follicles in low dose of endosulfan and
      malathion (11 mg kg(-1)) treated rats. The histologic observations of the ovary
      revealed the presence of less number of healthy follicles and more number of
      atretic follicles and corpus luteums in high dose of endosulfan and malathion (33
      mg kg(-1)) treated rats. Finally, a peroxidative damage occurs inavitably due to
      endosulfan and malathion for ovarium tissues. The biochemical results (MDA
      levels) also showed such a damage, similar with the histological results.

PMID- 19579999
TI  - Systematic study of Bromus danthoniae (Poaceae) native to Iran.
AB  - In this study different varieties of Bromus danthoniae in Iran are considered.
      Qualitative and quantitative morphological characters were evaluated for 32
      accessions. Epidermal features were also studied for these accessions. The most
      variable morphological characters in the species delimitation were also
      determined. The varieties show significant variations in features as Awn status,
      Spike and spikelet length, Nerve number of Upper Glume, Lemma, Palea and
      Caryopsis length. Diagnostic features based on studied characters are identified
      and the varieties relationships are discussed.

PMID- 19580000
TI  - Effects of NaCl stress on antioxidative enzymes of glycine Soja sieb.
AB  - The activity of anti-oxidant enzymes (Superoxide dismutase (SOD), Peroxidase
      (POD), Catalase (CAT) and parameters of oxidative stress malondialdehyde (MDA) of
      shoots were investigated in S. sieb naturally salt-resistant halophyte. The
      seedlings of S. sieb were treated with varying (0, 80, 160 and 240 mM) NaCl
      stress. The results showed that NaCl played an important role in growth of S.
      sieb. It made obviously promotion of certain NaCl concentration to growth of S.
      sieb, the seeflings of S. sieb grew best under 80 mM salt stress. MDA
      concentration of S. sieb obviously decreased under 80 mM salt stress then
      increased with salt concentration increased. The activities of SOD, POD and CAT
      increased with the increase of the concentration of NaCl in S. sieb. The salt
      tolerance of this halophyte under salt stress condition are probably due to its
      ability to exhibit high SOD, POD and CAT enzyme activities and Soluble Sugar (SS)
      concentration.

PMID- 19580001
TI  - On-admission level of serum d-dimer and the severity of community-acquired
      pneumonia.
AB  - This study aims at evaluating on-admission serum level of d-dimer in patients
      with community-acquired pneumonia concerning the severity of the disease and in
      hospital outcome of the patients. Sixty patients with community-acquired
      pneumonia were studied during a one-year period in Imam Khomeini and Sina
      Hospitals, Tabriz, Iran. On-admission serum d-dimer was measured by enzyme-linked
      immunoabsorbent assay and the severity of disease determined according to PORT
      grading system. In-hospital outcome was determined in regard to the level of
      serum d-dimer. Sixty patients with community-acquired pneumonia, 39 males and 21
      females were enrolled. There were twelve patients with PORT one, eight patients
      with PORT two, eight patients with PORT three, twenty patients with PORT four and
      twelve patients with PORT five. The mean level of serum d-dimer was significantly
      higher in severe disease (p < 0.001), patients with hospital stay longer than one
      week (p = 0.003), patients with bronchopulmonary pattern (p = 0.012), cases in
      need of mechanical ventilation (p < 0.001) and patients who expired during
      hospital stay (p = 0.022). On-admission level of serum d-dimer was significantly
      and independently higher in patients with severe disease (p < 0.001) and in cases
      with bronchopulmonary pattern on chest x-ray (p = 0.035). On-admission level of
      serum d-dimer may predict the severity of community-acquired pneumonia. Further
      studies are recommended for accurate cut-off points.

PMID- 19580002
TI  - Bacteriostatic effect of Piper betle and Psidium guajava extracts on dental
      plaque bacteria.
AB  - In this study, the bacteriostatic effect of Piper betle and Psidium guajava
      extracts on selected early dental plaque bacteria was investigated based on
      changes in the doubling time (g) and specific growth rates (micro). Streptococcus
      sanguinis, Streptococcus mitis and Actinomyces sp. were cultured in Brain Heart
      Infusion (BHI) in the presence and absence of the extracts. The growth of
      bacteria was monitored periodically every 15 min over a period of 9 h to allow
      for a complete growth cycle. Growth profiles of the bacteria in the presence of
      the extracts were compared to those in the absence and deviation in the g and
      micro were determined and analyzed. It was found that the g and mu were affected
      by both extracts. At 4 mg mL(-1) of P. betle the g-values for S. sanguinis and S.
      mitis were increased by 12.0- and 10.4-fold, respectively (p < 0.05). At similar
      concentration P. guajava increased the g-value by 1.8- and 2.6 -fold,
      respectively (p < 0.05). The effect on Actinomyces sp. was observed at a much
      lower magnitude. It appears that P. betle and P. guajava extracts have
      bacteriostatic effect on the plaque bacteria by creating a stressed environment
      that had suppressed the growth and propagation of the cells. Within the context
      of the dental plaque, this would ensure the attainment of thin and healthy
      plaque. Thus, decoctions of these plants would be suitable if used in the control
      of dental plaque.

PMID- 19580003
TI  - Anatomical variations of neurovascular structures adjacent sphenoid sinus by
      using CT scan.
AB  - The aim of this research was to study of the relationship between anatomical
      variations of neurovascular structures adjacent sphenoid sinus with sex and
      position of appearance by using CT scan. In this retrospective study paranasal
      sinuses CT scan has been taken from 399 patients (210 male, 189 female) that
      referred to Imam Khomeini and Apadana Hospitals, Ahwaz, Iran. Furthermore,
      protrusion and dehiscence of Internal Carotid Artery (ICA), Maxillary Nerve (MN),
      Vidian Nerve (VN) and Optic Nerve (ON) into the sphenoid sinuses cavity have been
      investigated by using CT scan results. In 210 male patients the protrusion of
      interested variables were noticed as: ICA in 102 (48.5%) cases, ON in 80 (38%)
      cases, MN in 74 (35.5%) cases, and VN in 60 (28.5%) cases, respectively. Also in
      189 female patients group the protrusion of ICA, ON, MN, VN were noticed in 65
      (34.3%), 66 (34.9%), 62 (32.8%) and 43 (22.7%) cases, respectively. The
      statistical analysis show significant difference (p = 0.001) of protrusion of ICA
      between male and female groups. In 210 male patients the dehiscence of ICA, ON,
      MN, VN were noticed in 82 (39%), 60 (28.5%), 60 (28.5%) and 66 (31.4%) cases,
      respectively. Also in 189 female patients the dehiscence of interested variables
      were noticed as: ICA in 85 (44.9%), ON in 87 (46%), MN in 69 (36.5%), VN in 71
      (37.5%) cases, respectively. The statistical analysis show significant difference
      (p = 0.03) of dehiscence of on variable in male and female groups. In order to
      increase the risk of intra-operative complications detailed preoperative
      investigation of neurovascular structures in sphenoid sinuses by use of CT scan
      images should be done properly.

PMID- 19580004
TI  - Differential expressed protein in developing stages of Nepenthes gracilis Korth.
      pitcher.
AB  - Nepenthes gracilis Korth. is a member of carnivorous plants in family
      Nepenthaceae. The plants have beautiful and economically important pitchers. It
      is interesting to study the protein(s) correlated with the pitcher. Crude
      proteins were extracted from leaf, leaf with developing pitcher and developed
      pitcher of the same plant and analyzed by Sodium Dodecyl Sulfate Polyacrylamide
      Gel Electrophoresis (SDS-PAGE). Two protein bands with molecular weights of 42.7
      and 38 kDa were obtained from young leaf and leaf with developing pitcher,
      respectively. The 42.7 kDa protein was identified as phosphoglycerate kinase
      (PGK) by Liquid Chromatography Mass Spectrometry (LC-MS/MS), but the 38 kDa band
      is an unknown protein. Both proteins were differentially expressed in each
      developing stage of the pitcher, thus may be powerful candidates play role in
      development pathway of leaf and pitcher.

PMID- 19580005
TI  - Evaluation of excreted/secreted antigens derived from peritoneal of toxoplasma
      infected small mice to detect IgG against Toxoplasma.
AB  - The present study, evaluated, using the components of peritoneal fluid of
      infected mice (as another source of E/SA), for the detection of Toxoplasma
      specific IgG in human serum. Peritoneal fluids of mice infected by
      intraperitoneal (IP) inoculation of Toxoplasma tachizoites were collected after 3
      days and centrifuged at 750 x g for 15 min then the supernatant was precipitated
      with ammonium sulphate solution (40% saturated) and used as components containing
      E/SA. Forty nine uninfected (without anti-Toxoplasma antibodies) and thirty two
      positive (with IgG to Toxoplasma) human serum samples were selected (all sera
      were first tested by standard method for detection of IgG antibodies anti-T.
      gondii) then the sera were tested by ELISA using E/SA. The cut-off point with 95%
      confidences was found to be 0.78. Moreover, sensitivity and specificity of the
      method were determined to be 84 and 92%, respectively. The present results
      indicate that peritoneal exudates from mice infected with T. gondii may be used
      as a source of antigenic material for the detection of Toxoplasma-specific IgG
      and may be valuable for the development of new tools in the serodiagnosis of
      toxoplasmosis.

PMID- 19580006
TI  - Using transposon mutagenesis to find an alternative resolvase in an Escherichia
      coli cells lacking RuvABC.
AB  - This study was undertaken to identify an unknown resolvase in an E. coli strain
      lacking RuvABC (N4237) by using transposon mutagenesis. One out of 10000 clones
      was retained for further study as it was resistant to UV light and mitomycin C.
      The result of transductional mapping and PCR sequencing showed that Tn10kan
      inserted upstream of rusA gene and expression of this gene improved survival.
      Thus, results did not show the presence of new resolvase in E. coli cells.

PMID- 19580007
TI  - The effects of planting methods and head pruning on seed yield and yield
      components of medicinal pumpkin (Cucurbita pepo subsp. Pepo convar. Pepo var.
      styriaca) at low temperature areas.
AB  - This experiment carried out to evaluate the effects of planting methods (seed
      sowing and transplanting) and head pruning (no pruning, pruning after 12th node
      and pruning after 16th node) on yield and yield components such as number of
      branches (sub-branches) per plant, fruits per plant, growth, fruit size, weight
      of fresh fruit, weight of seeds per fruit, number of seeds per fruit and seed
      yield of medicinal pumpkin. The experiment was carried out based of factorial
      experiment with Randomized Completely Blocks Design (RCBD) by three replications
      in Ardabil Agricultural and Natural Resources Researches Station at 2007.
      Seedlings were grown in heated greenhouse. When the climatic condition became
      suitable and seedlings were at the four leaves stage, both seeds and seedlings
      were planted at the same time in the farm. Maintenance operations were done
      during the growth season. Head pruning treatments were done the forecast time.
      The results showed that the planting methods had significant effect on the number
      of ripen fruits per plant, fruits diameter, weight of seeds per fruit, weight of
      1000 seeds and seed yield and had no significant effect on the other traits. Also
      the results indicated that head pruning treatments had significant effects on the
      number of branches per plant, growth and seed yield and no significant on the
      other traits. In this experiment the most seed yield (997.8 kg ha(-1)) obtained
      from transplanting method with head pruning after 12th node and the least seed
      yield obtained from control.

PMID- 19580008
TI  - Incidence of vertebral hemangioma on spinal magnetic resonance imaging in
      Northern Iran.
AB  - The incidence of vertebral hemangiomas as the most common benign spinal neoplasms
      has been differently reported from 10 to 27% based on autopsy series, plain X
      rays and MRI reviews. In this study, we reviewed consecutive 782 standard spinal
      MRI with axial and sagital T1 weighted and T2 weighted images looking for
      hemangiomas. In this study, the incidence of hemangioma was 26.9%, more common in
      females (30%) than males (23%), in older age group and in lumbar spine. Most
      hemangiomas (65%) were less than 10 mm in diameter. Multiple hemangiomas were
      seen in 33% of cases. The results of this study are similar to another
      Mediterranean study reported based on MRI findings, but differ from other reports
      using X-ray or autopsy as diagnostic tool, suggesting the influence of either the
      race or the sensitivity of the diagnostic tool on the incidence of vertebral
      hemangioma.

PMID- 19580009
TI  - Describing variation in rump P8 fat depth of crossbred cattle from birth to
      slaughter.
AB  - A Principal Component Analysis (PCA) was conducted on the matrix of correlations
      among P8 fat measures at seven different ages for steers and heifers. The P8 fat
      measures were collected from 1143 steers and heifer calves that were born to
      Hereford (h) dams inseminated with semen from seven different sire breeds: Angus,
      Belgian Blue, Hereford, Jersey, Limousin, South Devon and Wagyu, over a 4-year
      period (1994 to 1997). The first two principal components explained 61 and 57% of
      the total phenotypic variation in fatness for steers and heifers, respectively.
      The first component was positively correlated to all measures and was interpreted
      as a measure of overall fatness. The second component was positively correlated
      to fatness approximately pre-weaning and negatively correlated thereafter and
      thus was interpreted as maturity type but could be a function of milk supply.
      When estimated from a sire model, the heritability estimates were high for the
      first component (0.59 and 0.67 for steers and heifers, respectively) but low for
      the second component (0.05 and 0.19). The results demonstrate the value of
      combining information across multiple measurements to build accuracy, even when
      relatively crude methods are used.

PMID- 19580010
TI  - Evaluation of characteristics of patients with pilomatricoma in Mazandaran
      Province, 1996-2006.
AB  - The aim of this study was to evaluate characteristics of patients with
      pilomatricoma in Mazandaran Province, 1996-2006. In this study 46 case of
      pilomatricoma, with asymptomic, single and firm nodule referred to dermatology
      clinic of Boo-Ali Sina Hospital in Sari (1996-2006). A Biopsy was taken from
      suspicious lesions and histopathology assessments were done for cases with
      pilomatricoma impression. 69.56% patients were female. Mean age of the patients
      was 20.1 years .The most frequent sites of the tumor were the forearm (41.30%).
      It can be concluded, because the pilomatricoma is a benign cutaneous neoplasm
      with differentiation toward hair matrix, so that it is not seen in palm or
      plantar surface, but could present in any other area. Since, few of pilomatricoma
      lesions converted to malignant, so that it is better we resects total lesion by
      surgical excision.

PMID- 19580011
TI  - The role of different inoculum levels of Meloidogyne javanica juveniles on
      nematode reproduction and host response of peanut plant.
AB  - A pot experiment was conducted to determine the influence of three of inoculum
      levels (1000, 2000 and 3000 J2 pot(-1)) of Meloidogyne javanica on nematode
      reproduction and host response of peanut plant cv. Giza 4 under greenhouse
      conditions at 30 +/- 5 degrees C. In general, nematode reproduction and host
      damage were both affected by the initial inoculum levels. The greater reduction
      percentage of plant fresh (57.7%), shoot dry (38.82) and pods weights (52.59%)
      and nodules numbers (73.33%) were recorded at inoculum level 2000 J2/peanut
      plant, when rate of nematode build-up reached the maximum value of 1.64.
      Regression analysis of Pi vs. rate of nematode build-up on peanut plants gave
      value of R2 amounted to 0.3193. On the other hand, when the initial inoculum
      level added increased up to 3000 J2/peanut plant, the percentage reduction of
      whole plant fresh weight (47.07%) and other growth parameters as well as nematode
      build-up (0.8) also obviously decreased.

PMID- 19580012
TI  - Effect of DNA hypomethylation on genotoxicity and apoptogenicity of sodium
      arsenite in laboratory mice.
AB  - The present study aims to evaluate the effect of DNA hypomethylation state on
      genotoxicity and apoptogenicity induced by sodium arsenite (NaAsO2) in normal
      adult male SWR/J mouse bone marrow cells. Animals were treated with
      intraperitoneally (i.p.) injected with (2.25, 4.50 or 9 mg kg(-1) b.wt. of NaAsO2
      which represent 0.25, 0.50 or 1 of LD5, respectively) and killed 24 h later.
      Another different group of male mice was treated with three doses of 5
      Azacitidine (5-AzaC), 5 mg kg(-1) b.wt. each dose and 3 h intervals between them.
      NaAsO2 administered after 6 days of the last dose. The three single doses of
      sodium arsenite alone significantly (p<0.05) increased the rate of total
      structural Chromosomal Aberrations (CAs), rate of Sister Chromatid Exchanges
      (SCEs), micronucleus (MNs) formation, PARP and Lamia-A degradation and apoptosis
      as compared with the negative control. The combined treatment with
      hypomethylation agent 5-AzaC significantly increased the rate of SCEs induced by
      NaAsO2 at low dose. Moreover, this treatment significantly increased the rate of
      polyploidy at all combined used doses. Furthermore, this treatment induced
      apoptosis at all used doses. The present study has shown that DNA hypomethylation
      had a negative effects represented in rate of (CAs), polyploidy, PARP degradation
      and apoptosis induced by (NaAsO2). On the other hand, DNA hypomethylation had
      positive effects represented in decreas rate of pulverized chromosomes,
      centromeric attenuations, (SCEs), (MNs) formation, prevent Lamina-A degradation
      and apoptosis.

PMID- 19580013
TI  - Cytogenetical studies on achene colour polymorphism of Picris asplenoides L. and
      Urospermum picroides L. (Asteraceae) in Egypt.
AB  - Achene morphs of Picris asplenoides L. and Urospermum picroides L. were
      investigated in order to gain insight into its genetic variation based on the
      evidence obtained from karyotype analysis, electrophoretic pattern of achene
      proteins as well as nucleic acid analysis. In Picris asplenoides L., three achene
      morphs were observed from every inflorescence as follows: violet, brown and
      white, these morphs differ in their color. In the inflorescence of Urospermum
      picroides L., three achene morphs were differ also in their color were observed
      as follows: white, brown and black. All achene morphs of Picris asplenoides and
      Urospermum picroides were diploid, with ten chromosomes observed in somatic
      cells. Karyotype studies showed that the achene morphs of Picris asplenoides and
      Urospermum picroides have different karyotype formulae. However, the chromosome
      type nearly submetacentric (-) and nearly metacentric were common in all
      karyotype formulae of all different achene morphs of Picris asplenoides and
      Urospermum picroides. Not only the dissimilarity was found in the morphology of
      chromosomes but also in the Mean Chromosome Length (MCL) and Diploid Chromosome
      Length (DCL). Types and proportions of abnormalities for different achene morphs
      of Picris asplenoides and Urospermum picroides observed at mitotic division were
      analysed. The electrophoretic analysis of Picris asplenoides revealed the
      presence of fourteen bands of molecular weight ranging from 145.00 to 20.00 kD.
      The band with molecular weight 20.00 kD was restricted to brown achene from and
      can be used as molecular marker to distinguish brown achene form from violet
      achene form. The electrophoretic analysis of Urospermum picroides reveals the
      presence of nine bands of molecular weight ranging from 95.00 to 22.00 kD. The
      band with molecular weight 22.25 kD was restricted to white achene from and can
      be used as molecular marker to distinguish white achene form other achene forms.
      The nuclear DNA content for Picris asplenoides were 0.0295 and 0.0183 microg g(
      1) fresh weight for violet and brown achene, respectively, while RNA content were
      25.347 and 35.069 microg g(-1) fresh weight for violet and brown achene,
      respectively. The nuclear DNA content for Urospermum picroides were 0.093, 0.115
      and 0.145 microg g(-1) fresh weight for brown, black and white achene,
      respectively while RNA content were 10.417, 17.361 and 21.528 microg g(-1) fresh
      weight for black, white and brown achene, respectively.

PMID- 19580015
TI  - Effect of some antioxidants on canola plants grown under soil salt stress
      condition.
AB  - In this study, two field experiments were carried out during the two growing
      seasons (2005-2006 and 2006-2007) to investigate the role of some applied
      antioxidants (spermine 10 mg L(-1) and ascorbic acid 200 mg L(-1)) in
      counteracting the harmful effect of soil salinity stress (10.1 or 14.6 dS m(-1))
      on canola plants. Growth characters, yield and its components as well as
      biochemical constituents were studied in the two growing seasons. The results
      showed that all growth characters including; plant height, leaves number and
      area/plant, shoot and root dry weight as well as yield and its components
      including; fruit number/plant, number of fruiting branches, seed number/fruit,
      seed yield/plant and seed oil content of canola plant were decreased with
      increasing soil salt level (A2) comparing with (A1). On the other hand, applied
      antioxidants spermine 10 mg L(-1) and ascorbic acid 200 mg L(-1)) increased
      growth and yield of canola plant during the two growing seasons. However, the
      applied antioxidants were more effective under the first soil salt condition (A1)
      soil salt stress levels (A2) decreased each of photosynthetic pigments, K and P
      contents, while increased proline, soluble sugar, ascorbic acid, Na and Cl
      contents compared with (A1). On the other hand, applied antioxidants increased
      each of photosynthetic pigments, proline, soluble sugar, N, K and P contents,
      while decreased Na and Cl contents in canola plant under soil salt stress (A1 and
      A2) during the two growing seasons. It could be concluded that applied
      antioxidants could counteract the harmful effect of salt soil stress on growth,
      yield and biochemical constituents of canola plant.

PMID- 19580014
TI  - The perspective effects of various seed coating substances on rice seed variety
      Khao Dawk Mali 105 storability II: the case study of chemical and biochemical
      properties.
AB  - The aim of this study was to investigate the effects of seed coating substances;
      chemical fungicide (CA) and biological fungicide polymers [chitosan
      lignosulphonate polymer (CL) and eugenol incorporated into chitosan
      lignosulphonate polymer (E+CL)] on chemical and biochemical changes of rice seeds
      cv. KDML 105, which have been studied during storage for 12 months. CA
      significantly affected the rice seed chemical properties and the associated seed
      deterioration. After 12 months storage, protein content decreased accompanied by
      declined of lipid content, increased free fatty acids and activated lipoxygenase
      enzyme. In the case of biological fungicide coated seeds, the antioxidative
      scavenging enzymes were ascorbate peroxidase and superoxide dismutase and a high
      antioxidant activity protected them. Moreover, the sugar content was positive
      correlated with seed germination and vigor. The biological coated seeds were
      found to maintain high sugar contents inside the seeds, which resulted high seed
      storability significantly. In contrast, under fungicide stress (CA), those
      compounds were lost that directly affected seed vigor during storage.

PMID- 19580017
TI  - Investigation of the analgesic and antioxidant activity from an ethanol extract
      of seeds of Sesamum indicum.
AB  - The present study was intended to investigate the analgesic and antioxidant
      activity of ethanol extract of seeds of Sesamum indicum (Linn.) (family:
      Pedaliaceae). It was observed that the extract showed a significant inhibition on
      the writhing response produced by induction of acetic acid. The intensity of
      writhing inhibition of the extract was increased with the increase of dose. The
      extract produced about 48.19 and 75.46% writhing inhibition at the doses of 250
      and 500 mg kg(-1), respectively, which was comparable to the standard drug
      ibuprofen where the inhibition was about 71.82% at the dose of 25 mg kg(-1). This
      study also intended to investigate the antioxidant property of the ethanolic
      extract of this sample. The ethanol extract showed 92.00% inhibition and 56.00%
      reduction ability in hydrogen donation and reducing power assays, respectively at
      maximum concentration of the extract tested. The antioxidant activity of the
      extract in all these in vitro assays was compared with standard antioxidant
      (ascorbic acid).

PMID- 19580016
TI  - Mycobiota and concentration of ochratoxin A in concentrated poultry feed from
      Venezuela.
AB  - The main objective of this study was to evaluate the frequency distribution of
      mycobiota and the concentration of Ochratoxin A (OTA) in 50 samples from one
      company of commercial brand poultry feed produced in Venezuela. The concentration
      of OTA in the samples analyzed was determined using the competitive ELISA method.
      The most frequently isolated genera of moulds were Aspergillus (36%) and
      Penicillium (20%). Of these genera, the most frequently isolated species were
      Aspergillus flavus, Aspergillus terreus and Penicillium citrinum. Ochratoxigenic
      species such as Eurotium herbariorum, Aspergillus niger, Aspergillus ochraceus
      and Aspergillus glaucus, were also found with lower frequency. Rhodotorula
      mucilaginosa was the only yeast isolated. 94% of the samples presented
      contamination by OTA in a range between 2.558 and 31.978 microg kg(-1) feed and
      42% of them presented OTA levels from 10 up to 20 microg kg(-1). The findings of
      this investigation show that 84% of the samples of concentrated feed for meat
      poultry surpass the maximum permitted limit for OTA of 5 microg kg(-1),
      established in the majority of countries in which regulations are placed.

PMID- 19580018
TI  - In vitro antibacterial and cytotoxic activities of different parts of plant
      Swietenia mahagony.
AB  - Crude extracts from different parts (leaf, bark and seed) of Swietenia mahagony
      (Family: Meliaceae) were screened for their antibacterial activity against 4 Gram
      positive and 8 Gram negative bacteria. Disc diffusion technique was used for in
      vitro screening. Among the crude extracts, chloroform and ethyl acetate extracts
      of leaf and bark showed good activity against all the tested organisms. The
      chloroform and ethyl acetate extracts of seed exhibited little or positive effect
      against most of the tested bacteria. The activities were compared to a standard
      antibiotic-kanamycin. Cytotoxic activity of crude extracts were determined using
      brine shrimp lethality bioassay and standard vincristine sulphate was used as
      positive control. The chloroform extract of seed and ethyl acetate extract of
      bark showed good cytotoxic activities and the LC50 values were found 13.75 and
      11.64 microg mL(-1), respectively.

PMID- 19580019
TI  - Effect of scalp infiltration with Bupivacaine on early hemodynamic responses
      during craniotomy under general anesthesia.
AB  - The present study was conducted to evaluate the effect of scalp infiltration with
      Bupivacaine on hemodynamic responses during early stimulation in craniotomy under
      general anesthesia. Thirty six patients were prospectively randomized to receive
      Bupivacaine scalp infiltration (B group) or a saline control (S group) as an
      adjuvant to general anesthesia using isoflurane in 50% N2O-O2. Mean Arterial
      Blood Pressure (MAP) and Heart Rate (HR) were recorded as base line, after scalp
      incision or pin insertion and then every 3 min until 12 min. The measurements
      were repeated every 5 min till dura was opened. The mean difference between the
      two groups for HR during scalp incision or pin insertion was significant (p =
      0.03). The mean MAP throughout the time intervals of preincision or pin insertion
      to 12 min postincision and then to dural opening were statistically different
      between the two groups (p = 0.001). No complications related to the technique of
      block or drugs were recorded. Scalp infiltration with Bupivacaine as an adjuvant
      to general anesthesia can provide more stable hemodynamics, as measured by HR and
      MAP changes during early stimulation in craniotomy.

PMID- 19580020
TI  - Hopes, doubts about stimulus provisions.

PMID- 19580021
TI  - Measuring ROI.

PMID- 19580022
TI  - Fighting for every dime.

PMID- 19580023
TI  - The payer role in HIEs.

PMID- 19580024
TI  - Keeping personal health records.

PMID- 19580025
TI  - Taking on the big boys.

PMID- 19580026
TI  - Focusing on quality data.

PMID- 19580027
TI  - Graduate students as local government scientific advisors.

PMID- 19580028
TI  - The role of halogen.

PMID- 19580029
TI  - Human modification of a large meandering Amazonian river: genesis, ecological and
      economic consequences of the Masisea cutoff on the central Ucayali, Peru.
AB  - Evidence is mounting regarding the significant extent and scope of long-term
      human modification of "pristine nature" in the neotropics. In Amazonia, recent
      studies point to the landscape imprint of human activity that has transformed the
      forests, savannas, soils, and waterways of the basin. In this report, we describe
      a massive meander cutoff in the Peruvian Amazon along the Ucayali River--the
      fifth-longest river in the Amazon basin--that was triggered by small-scale human
      actions and resulted in significant ecological and economic consequences for the
      region. The modern case of the Masisea cutoff-near the Amazonian port city of
      Pucallpa, Peru (285,000 inhabitants)-indicates that humans using simple tools can
      play a major role in transforming large meandering rivers and their floodplains.

PMID- 19580030
TI  - Costs of alien invasive species in Sweden.
AB  - The purpose of this paper is to present calculations of total costs of 13 alien
      invasive species (AIS) in Sweden. All species are subject to control by Swedish
      public authorities, and estimates for most AIS include either damage cost or
      actual control cost. The results indicate a total annual cost between
      approximately 1620 and 5080 million SEK, which correspond to SEK 175 and SEK 565
      per capita in Sweden. The estimates are well within the range of similar
      calculations for other countries, but differ with respect to the composition of
      costs of different AIS. Whereas costs for the agricultural and forestry sectors
      dominate in most other studies, the costs of AIS in Sweden are more equally
      divided among different categories. The results also indicate that the highest
      costs are attributable to unintentionally introduced AIS and that the most
      reliable cost estimates are related to human and animal health.

PMID- 19580031
TI  - South America's neoliberal agricultural frontiers: places of environmental
      sacrifice or conservation opportunity?
AB  - Neoliberal agricultural frontiers, defined as export-oriented farming areas
      motivated more by global demand and land privatization than by government
      subsidies, present at least two major challenges for environmental researchers:
      estimating land change and understanding governance types and outcomes.
      Environmental governance, the "filter" between human and biophysical systems, is
      considered in terms of two models in light of empirical evidence from a
      neoliberal frontier in the Brazilian Cerrado (savanna) ecoregion. Land-change
      analysis indicates that agricultural land uses increased from 12% of the study
      region in 1986 to 44% in 2000 and 55% in 2005, with a corresponding loss of
      native Cerrado. A prominent farming organization formed in 1990 has participated
      in or led several environmental policy initiatives. Evidence of both governance
      models is found, and dilemmas facing environmental activists and managers, as
      well as the farming sector, are presented. For organizations representing large
      commercial farmers, compliance with environmental regulations may be seen as both
      a cost to be borne by the farming sector and as a means to establish
      environmental credentials. Suggestions are made for future longitudinal work on
      compliance, information, agenda-setting, and discursive strategies of nonstate
      actors in neoliberal frontiers.

PMID- 19580032
TI  - Recent land degradation and improvement in China.
AB  - Land degradation is a global development and environment issue that afflicts
      China more than most countries in terms of the extent, economic impact, and
      number of people affected. Up-to-date, quantitative information is needed to
      support policy and action for food and water security, economic development, and
      environmental integrity. Data for a defined, recent period enable us to
      distinguish the legacy of historical land degradation from what is happening now.
      We define land degradation as long-term decline in ecosystem function and
      productivity and measure it by remote sensing of the normalized difference
      vegetation index (NDVI), the greenness index. NDVI may be translated to net
      primary productivity (NPP). Deviation from the norm serves as a proxy assessment
      of land degradation and improvement-if other factors that may be responsible are
      taken into account. These other factors include climate, which may be assessed by
      rain-use efficiency and energy-use efficiency. Analysis of the 23-year Global
      Inventory Modeling and Mapping Studies (GIMMS) NDVI data reveals that, in China
      over the period 1981-2003, NPP increased overall, but areas of declining climate
      adjusted NPP comprise 23% of the country, mainly in south China. About 35% of
      China's population (457 million out of 1317 million) depend on the degrading
      land. Degrading areas suffered a loss of NPP of 12 kgC ha(-1) y(-1), amounting to
      almost 60 million tC not fixed from the atmosphere; loss of soil organic carbon
      from these areas is likely to be orders of magnitude greater. There is no
      correlation between land degradation and dry lands; it is more of an issue in
      cropland and forest: 21% of degrading land is cropland and 40% is forest, 24% of
      the arable and 44% of the forest, respectively. There is no simple statistical
      relationship between land degradation and rural population density or poverty.
      Most identified land degradation is in the south and east, driven by
      unprecedented land-use change.

PMID- 19580033
TI  - Spatial assessment of water use in an environmentally sensitive wetland.
AB  - Wetlands are among the most valuable ecosystems in the world and are crucial in
      supporting biodiversity. They also provide space for storing surface waters,
      where intense biological processing occurs that helps improve water quality.
      Human activities, particularly irrigated agriculture and urban developments
      instigating water diversions from rivers, have altered the hydrology of most
      wetlands. The Lower Murrumbidgee wetland, located in the Murrumbidgee River
      Catchment, is an example and is one of the significant wetlands across the Murray
      Darling Basin of Australia. Historic estimates show the volumes of water ranged
      from none in dry years to about 300 to 400 GL (1 GL = 10(9) L) in an average and
      wet year, respectively. The flows reaching the Lower Murrumbidgee wetland have
      been drastically reduced by at least 60% because of the upstream diversions
      introduced during the last century. These reductions have adversely affected the
      health of natural vegetation and agricultural crops in the Lower Murrumbidgee
      floodplain. This article presents the results of the quantification of total
      water consumption of various land uses in the Lower Murrumbidgee floodplain using
      the remote sensing-based Surface Energy Balance Algorithm for Land (SEBAL)
      modeling approach. The spatial analysis of actual evapotranspiration (ETa) shows
      that ETa rates are the highest (13-26%) for the red gum (Eucalyptus
      camaldulensis) forests both in summer and winter days. However, in terms of total
      ETa volume, lignum (Muehlenbeckia florulenta) constitutes the most significant
      part, which is around 14-30% of the total ETa volume for the area. Actual
      evapotranspiration from winter cereal cropping areas following the summer ponding
      is the third highest consumer of water after the river red gum and lignum. Actual
      evapotranspiration from the fallow land is also significant, representing 5-28%
      of total ETa from the region. In view of the extent of the unaccounted flows in
      the overall water balance of the system, there is a need to upgrade measuring and
      reporting infrastructure by strengthening the institutional and management
      arrangements to better gauge the efficiency of environmental and consumptive
      water use. The state-of-the-art technology of remote sensing-based SEBAL modeling
      proved to have potential for measuring actual water use with reliable accuracy
      and can be used for assessing the environmental and productive use of water from
      wetlands in other regions of Australia.

PMID- 19580034
TI  - Status, ecology, and conservation of the Himalayan griffon Gyps himalayensis
      (Aves, Accipitridae) in the Tibetan plateau.
AB  - The dramatic population crashes of 3 species of Gyps vulture have raised concerns
      about the status of their lesser-known congeners. Among these is the Himalayan
      griffon, G. himalayensis, an iconic vulture of the Tibetan plateau. The continued
      existence of this scavenger has not only ecological but also cultural
      implications because of their unique role in the centuries-old sky burial
      tradition that is followed by nearly 5 million Tibetan people. A lack of baseline
      information of the Himalayan griffon limits our ability to take conservation
      measures. The presented data, which were collected during 1996 and 2004 to 2007,
      indicate that this species is still widespread throughout the plateau and has not
      experienced a major population decline, likely as a result of protection by
      Tibetan Buddhism and limited disturbances from human activities largely due to
      the remoteness of the plateau. Both site and road counts showed that open meadow
      habitats had the highest griffon abundance, followed by alpine shrub and forest
      habitats. Estimates based on road transect counts showed that 229,339 Himalayan
      griffons (+/- 40,447) occupy the 2.5 million km2 Tibetan plateau. In contrast,
      the maximum carrying capacity of the plateau, on the basis of the total biomass
      of potential food resources, is 507,996 griffons, with meadow habitats accounting
      for about 76% of the total population. Griffons depend largely on livestock
      carcasses for food and forage in groups averaging 5.5 (range 1-100) individuals.
      Domestic yaks provide about 64% of the griffons' diet, while wild ungulates and
      human corpses provide 1% and 2%, respectively. Compared with its lowland
      congeners, this, the only high-elevation Gyps species, had both low population
      density and small group size, a likely response to the harsh environmental
      conditions. Although griffon abundance appears relatively stable in their fairly
      pristine environment, precautionary measures, including investigation of threats,
      monitoring of population dynamics, and establishment of modern conservation
      consciousness among Tibetan Buddhists, should be carried out to ensure that this
      abundance continues.

PMID- 19580035
TI  - Large-scale species introductions to preserve global biodiversity: Noah's Ark
      revisited.

PMID- 19580036
TI  - Assessment of total suspended particulate matter-bound polychlorinated biphenyls
      in ambient air of a seasonally dry tropical urban-industrial area.

PMID- 19580037
TI  - Ecological restoration in west China: problems and proposals.

PMID- 19580038
TI  - Counter of energy conservation and emission reduction for the public in China.

PMID- 19580039
TI  - Banana crop expansion and increased river-borne sediment exports to the Gulf of
      Uraba, Caribbean coast of Colombia.

PMID- 19580040
TI  - Workflow streamlined, automated. An acute care facility implements a back-office
      solution to deal with repetitive tasks and to maximize its intranet.

PMID- 19580041
TI  - Data center opportunities. An interoperability platform maintains existing IT
      "bright spots" while providing secure access to patient information.

PMID- 19580043
TI  - Health plans tackle DM. Software innovations enable health plans to structure
      results-driven disease-management programs and demonstrate true ROI.

PMID- 19580042
TI  - Improve clinical communication. A university medical center implements a new
      communications system for rapid delivery of critical information.

PMID- 19580044
TI  - Deliver tangible ROI. Three healthcare organizations see reduced costs, enhanced
      efficiency and increased compliance with CPOE systems.

PMID- 19580045
TI  - [Nursing, teaching, more and always].

PMID- 19580046
TI  - [National Journal of neonatology, the child and even the individual].

PMID- 19580047
TI  - [Breast feeding and ethics].

PMID- 19580048
TI  - [Cerebral palsy, guiding the research by studying the needs].

PMID- 19580049
TI  - [Congenital handicaps: is it supposed to disappear?].

PMID- 19580050
TI  - [Attending the diabetic child. A multidisciplinary connection adapted to each
      child and his family].

PMID- 19580051
TI  - [Type 1 diabetes in children and adolescents].

PMID- 19580052
TI  - [Is ketoacidosis avoidable in the child with type 1 diabetes?].

PMID- 19580053
TI  - [Care of type 1 diabetes in children and adolescents].

PMID- 19580054
TI  - [Initial therapeutic education in the diabetic child].

PMID- 19580055
TI  - [Notification of infantile diabetes and family reactions].

PMID- 19580056
TI  - [Return to home of the diabetic child after hospitalization].

PMID- 19580057
TI  - [Feeding, pleasure and childhood diabetes].

PMID- 19580058
TI  - [Group therapy and education for children with type 1 diabetes and their
      parents].

PMID- 19580060
TI  - [Individualized welcome project for the diabetic child].

PMID- 19580059
TI  - [Solace for pain in the child with diabetes].

PMID- 19580061
TI  - [Society of parents of children with diabetes for finding each other exchanging
      ideas].

PMID- 19580062
TI  - [4/12. Childhood asthma].

PMID- 19580063
TI  - [4/6.Embryo research].

PMID- 19580065
TI  - Increasing inpatient beds: a team effort.

PMID- 19580064
TI  - Providing an exit from case management.

PMID- 19580066
TI  - Working to reunite families torn apart by mental illness.

PMID- 19580067
TI  - Short-term solutions with long-term benefits.

PMID- 19580068
TI  - Reorganizing to provide integrated care.

PMID- 19580070
TI  - On the threshold of hope.

PMID- 19580069
TI  - If you build it, they will come.

PMID- 19580071
TI  - Keep up to date on ARRA funding.

PMID- 19580072
TI  - Managed care: key to a transformed system.

PMID- 19580073
TI  - Time to stop being one-dimensional.

PMID- 19580074
TI  - Committed to helping others.

PMID- 19580075
TI  - Telemedicine. Mobile video systems link ED with ambulances to jump-start triage.

PMID- 19580076
TI  - Legislation. Post-acute providers see health IT money slip away.

PMID- 19580077
TI  - Other voices. Building health care's Shangri-la of innovation. Interview by Haydn
      Bush.

PMID- 19580078
TI  - Patient care. Clinicians call for better coordination of women's health in rural
      areas.

PMID- 19580079
TI  - Supply chain. Economic collapse spurs creative thinking.

PMID- 19580080
TI  - The extra mile. Laughing all the way to a healthier life.

PMID- 19580081
TI  - Nursing. AARP effort to champion nursing shows results.

PMID- 19580082
TI  - Recession reaction. What the economic downturn means to hospital and health
      system CEOs.

PMID- 19580083
TI  - Mass. appeal?
AB  - Many health care experts describe Massachusetts' efforts at health care reform as
      a noble experiment that has sharply reduced the number of uninsured residents in
      the state. On the other hand, it has raised costs, threatened safety-net
      providers and brought other unintended consequences. What are the lessons for
      national reform?

PMID- 19580084
TI  - Pumping new life into cardiovascular.

PMID- 19580086
TI  - To survive, small hospitals give up independence.
AB  - Executives and boards ask: Is affiliating with a larger organization right for
      us? How do we make it work?

PMID- 19580085
TI  - Pediatric safety.
AB  - Caring for children raises different quality and safety issues. This foldout
      looks at four critical risk factors and whether pediatric hospitalists are right
      for you.

PMID- 19580087
TI  - The sooner, the better.

PMID- 19580088
TI  - Building trust in a time of crisis.

PMID- 19580089
TI  - Empowering leaders and consumers through simplified pricing.

PMID- 19580090
TI  - Using transparency to tell your story.

PMID- 19580091
TI  - A competitive advantage in the capital market.

PMID- 19580092
TI  - Engaging patients with user-friendly data.

PMID- 19580093
TI  - One state's big goal: no HAIs.

PMID- 19580094
TI  - The future is finally here.

PMID- 19580095
TI  - Intensive care ventilators.

PMID- 19580096
TI  - Hazard Report. Medical vacuum system connection to ventilator breathing circuit
      may have contributed to patient's death.

PMID- 19580097
TI  - Hazard Report. Interpretation errors or repeat exposures may be caused by
      difficulty in correcting information on Hologic Selenia digital mammography
      systems.

PMID- 19580098
TI  - Hazard Report. Failure of Mizuho OSI Advanced Control Pad system may go
      undetected.

PMID- 19580099
TI  - Should patients diagnosed with polycystic ovary syndrome (PCOS) participate in
      compensated egg sharing in return for subsidized fertility treatment?

PMID- 19580100
TI  - Assisted procreation and its relationship to genetics and eugenics.
AB  - The article below is intended to reflect on whether or not a eugenic tendency
      constitutes an intrinsic element of human fertilization in vitro. The author
      outlines ideas and circumstances which characterized the foundation and
      propagation of eugenics between the eighteenth and nineteenth centuries. A brief
      discussion follows on some of the standard procedures of in vitro fertilization,
      and in particular, those which manifest a trace or hint of eugenics--heterologous
      fertilization and sperm banking, preimplantation genetic diagnosis (PGD) and
      embryo selection--practices which, nonetheless, are used on a large scale and
      shed light on both the essence of procreative medicine and on the current
      cultural environment. The objective of the article is to explore whether it is
      possible to eliminate the eugenic connotations without foregoing the benefits of
      technical and scientific progress.

PMID- 19580101
TI  - Science, biomedical technology and biolaw.
AB  - Starting from legislative recognition of the grounding principles of human
      rights, the authors describe and comment upon the Council of Europe's Convention
      on human rights and human dignity confronted with scientific discoveries and also
      upon the Oviedo Convention of 1997 for the protection of Human Rights and dignity
      of the human being with regard to the application of biology and medicine. The
      authors specify that, given the promise made by Romania to observe international
      obligations, the Romanian law no. 2/1998 on organ and tissue transplantation
      abrogates the stipulations of the law 3-1978 and also includes 9 appendices
      which, being part of the law, guarantee in addition the observance of its
      provisions. All these regulations on the relationship between science and human
      rights have determined an evolution from the fatality of natural risks to current
      compensations, as an expression of human solidarity. They have determined the
      transition from social and vocational paternalism to personal autonomy and
      personal guarantees of independence and freedom. All these developments are
      faithfully reflected by comparative legislation on the use of life science
      outcomes on persons as they presently are. This is also reflected in Romanian
      legislation concerning tissue and organ transplantation and in mental health
      legislation.

PMID- 19580102
TI  - Twin conception (didimogenesis) and ensoulment.

PMID- 19580103
TI  - Hot topic: clinical judgement versus evidence-based or informed practice.

PMID- 19580104
TI  - Patients' experiences with cognitive changes after chemotherapy.
AB  - Being diagnosed with cancer and undergoing treatment can be a daunting
      experience. The side effects of treatment often influence a person's quality of
      life. One side effect that has been identified more recently is known as
      "chemobrain." Although attempts have been made to quantify and measure cognitive
      changes, little attention has been paid to describing the changes from the
      patient's viewpoint. This investigation was undertaken to understand the impact
      of cognitive changes on daily living and to identify the strategies patients used
      to cope with "chemobrain." Thirty-two individuals provided in-depth interviews
      about their experiences living with cognitive changes. Their descriptions
      provided clear evidence that the changes could effect daily living, social and
      work-related activities. About a quarter of the individuals expected the changes
      to be temporary while the rest were uncertain or expected the change to be
      permanent. The emotional distress people experienced was linked to whether or not
      the cognitive changes interfered with their doing something that was of
      importance to them. Overall, participants used a variety of strategies to cope
      with the changes. The most frequently identified strategy was "writing everything
      down." When asked what nurses could do to assist them in managing this side
      effect, participants emphasized how important it is for them to have information
      about the potential for cognitive change at the beginning of their treatment.

PMID- 19580106
TI  - It is time for oncology nurses and researchers to work together to address the
      unique needs of the geriatric oncology population.

PMID- 19580105
TI  - Understanding the role of cancer informational support in relation to health care
      service use among newly diagnosed individuals.
AB  - A qualitative study was undertaken to explore the role of informational support
      in relation to health care service use among individuals with cancer. In-depth
      interviews were conducted with participants (N = 20) newly diagnosed with either
      breast or prostate cancer receiving radiotherapy from an oncology clinic in
      Montreal, Quebec. Content analysis revealed that participants' perceptions about
      their experience with cancer informational support in relation to health care
      services varied along the following dimensions: (1) Cancer informational support
      was tangible, which enabled, confirmed, normalized, and directed their decisions
      about reliance on health services; (2) Cancer informational support was somewhat
      paralyzing, which led to distress, conflict, reduced confidence in the health
      care system and, at times, misuse of health care services; and (3) Cancer
      informational support was limiting, with perceptions of having received both
      helpful and unhelpful cancer information which, in turn, although tolerated,
      offered little guidance in terms of reliance on the most appropriate services.
      Knowledge about how and when informational support may be most timely may
      optimize individuals' well being and further guide their use of cancer-related
      services.

PMID- 19580107
TI  - Precepts of community health and hygiene from the Holy Bible.
AB  - Every Society, in its unending process of evolution, devises its own methods of
      survival in ethical, medical and emotional aspects. The urge for good and healthy
      living, the desire for longevity of life are not only inherent but also largely
      evident in all the societies right from the time of its primitivity. Jews are a
      wonder community. Though negligible in numbers, they managed to win 17.5% of
      noble prizes announced so far. Besides, almost all the major inventions in the
      world are by Jews. This despite the years of persecution and trials the community
      was subjected to in the history. The pages of the human history are smeared with
      the blood patches of the Jews in the hands of oppressors for several centuries.
      Apart from the fact that theirs is the community chosen specially by God, the
      intellectual prowess and tenacity of the Jewish community basically stems from
      the discipline and dietary code they received from their leader Moses in
      wilderness. Jewish nation was conceived in the vision of their patriarch Abraham
      but in fact, born on the night they left as slaves from Egypt for good under the
      dynamic leadership of Moses. Mosaic code for all aspects of life has made Jews or
      Israelites what they are today. A modest effort is being made in this article to
      trace their community's health and hygiene social behavioral precepts as given by
      Moses.

PMID- 19580108
TI  - Pasu Ayurveda (veterinary medicine) in Garudapurana.
AB  - The history of veterinary medicine is closely tied to the development of human
      medicine. Evidence of animal medicine has been found in ancient civilizations,
      such as those of the Hindu, Babylonians, Hebrews, Arabs, Greeks, and Romans.
      Ancient Indian literature in the form of the holy Veda, Purana, Brahmana, epics,
      etc. is flooded with information on animal care. The Purana are ancient
      scriptures discuss varied topics like devotion to God and his various aspects,
      traditional sciences like Ayurveda, Jyotisa (Astrology), cosmology, concepts like
      dharma, karma, reincarnation and many others. The treatment of animal diseases
      using Ayurvedic medicine has been mentioned in Garudapurana, Agnipurana, Atri
      samhita, Matsyapurana and many other texts. The Garudapurana is one of the
      important Sattvika purana, the subject matter is divided into two parts, viz.
      Purvakhanda (first part) and an Uttarakhanda (subsequent part). Gavayurveda,
      Gajayurveda narrated briefly and Asvayurveda described detailly in Purvakhanda.

PMID- 19580109
TI  - Health promotion, preventive and curative aspects of diseases in astrology.
AB  - The whole universe is intermingling into a unit in the period of globalization.
      Different cultures, life-styles and sciences are co-operating with each other in
      this situation. World Health Organization is working towards collaborating all
      prevalent medical sciences for attainment of good health and family welfare for
      each and every individual by 2020. Astrology is a part of Indian heritage.
      Astrology means the art of predicting or determining the influence of the planets
      and stars on human affairs. The origin of this word is from Greek word astron,
      star + logos (discourse). The account of deeds of good and bad during the present
      life and previous lives, their consequences of health or ill health during this
      life i.e. what, when and how the things takes place will be clearly known through
      Astrology. Highly advanced knowledge related to Astrology on medicine is
      preserved in Indian scriptures and the knowledge was transmitted from generation
      to generation. It is also a good source for health promotion, preventive,
      curative and other medical aspects. Brief direction related to astrological
      medical aspects is also available in Ayurvedic literature (Carakasamhita,
      Susrutasamhhita, Astangasangraha, Astangahrdaya, Sarngadharasamhita , Bavaprakasa
      etc.) Some Ayurvedic practitioners, scholars and scientists realize the need of
      astrological knowledge related to medicine in the present time. In ancient times
      physician, astrologer and purohita (Hindu priest) simultaneously looked after the
      health and family welfare of individual, families and country. Astrologer guides
      medication and suitable time for the better cure of ailments. Even the medicinal
      herbs were collected and treated at appropriate time for their efficacy.
      Astrology and Ayurveda are inseparable sciences of life. Hence, in this article,
      a concise astrological evaluation related to health promotion, preventive and
      curative aspects of Astrology is being presented.

PMID- 19580110
TI  - Historical review of Svarna Maksika.
AB  - The old age Ayurvedic claim about the therapeutic importance of metals and
      mineral bhasmas are time tasted. To make available the evidence for use of metals
      and minerals in therapeutics and to provide the knowledge of processing
      techniques in ancient India it is very much necessary to look over the history.
      Rasa sastra is the branch of Ayurvedic science which deals with the
      pharmaceutical processings of the metals and minerals. Svarna Maksika is one of
      the most important materials described in various Rasa literatures as well as in
      Sarmhitas and in other Ayurvedic texts. Going through the different literatures
      its different features, geological distributions and various processing
      techniques like sodhana, marana are found. In Samhita period only the features
      were described but during 7th Cen. AD & onwards its processings were found. Now a
      day Svarrna Maksika is correlated with chalcopyrite by modern metallurgists. The
      features of chalcopyrite are also given to assist the more study in this regard.
      In the current paper it is tried to collect and compile all the related area
      about Svarna Maksika from all possible ancient literary resources as well as from
      possible modern texts, to facilitate further research.

PMID- 19580111
TI  - Medico-historical review of Nyagrodha (Ficus bengalensis Linn.).
AB  - Nyagrodha the Banyan tree (Ficus bengalensis Linn.) is a sacred medicinal plant
      since Vedic times. The English name Banyan is given by the Britishers to this
      tree because under the tree Banias i.e., the Hindu merchants used to assemble for
      business. The triad Ganges, the Himalayas and the Banyan tree are symbolise the
      images of India, hence it is considered as National Tree. Ficus means fig and
      bengalensis means belonging to or is of Bengal. To the most of Indians it is
      Sacred and symbolizes all three Gods of Hindus. The bark represents Lord Visnu,
      Brahma the roots and Siva the branches. Since Vedic times its small branches are
      used in Yajna (a sacrificial rite) and known for its giant structure. Alexander
      the Great is said to have camped under a banyan tree, which was big enough to
      shelter his whole army of 7,000 men. As per Veda it checks the environmental
      pollution and one of the source of Laksa (Lac). Its medicinal importance is well
      documented in Ayurveda literature. However, more research needs for understanding
      the medicinal properties of this symbolic tree.

PMID- 19580112
TI  - [Translational medicine and animal studies].

PMID- 19580113
TI  - [Pharmacies in Byzantium].

PMID- 19580114
TI  - 75th Anniversary of the Stiles-Crawford Effect(s): a celebratory special
      symposium, October 23, 2008; Rochester, New York.
AB  - There are rather few articles which, so-to-speak, serve to change the landscape
      in a scientific field. One of those was the discovery of the "directional
      sensitivity of the retina" by Walter Stanley Stiles and Brian Hewson Crawford
      (first reported in 1933). Subsequently, their findings were subdivided by Hansen
      into two logical components, "the Stiles-Crawford Effects of the First and Second
      Kinds, (SCE- 1 and SCE-2)." The former (SCE-1) dealt with aspects of their
      research which addressed alterations in perceived brightness of a visual
      stimulus; the second (SCE-2) was associated with the perceived hue and saturation
      of these visual stimuli. These discoveries arose out of a failed attempt by W.S.
      Stiles and B.H. Crawford to measure properly the areas of the entrance pupils of
      their experimental subjects as part of a research program which addressed
      problems of glare, e.g., disability glare, in illuminating engineering. Their
      research was conducted at the National Physical Laboratory (NPL), which is
      located in Teddington, Middlesex, England. These two fine scientists properly
      deduced the reason for the failure of their experimental design, and they
      effectively described and defined a new feature of the visual system which was
      largely ascribed to the retina. In time, it was realized that this phenomenon was
      associated in large measure with the waveguide/fiber-optics properties of
      photoreceptors, and that this was a feature shared by virtually all vertebrate
      species. This paper is divided into two parts. In the first part, Enoch
      describes, as best he can, the culture and working conditions at NPL during
      1959/60 when he served as a post-doctoral fellow with W.S. Stiles. And in the
      second part of this paper, the authors describe the findings of W.S. Stiles and
      B.H. Crawford at the time of their discovery. Today, we celebrate the 75th
      Anniversary of that research. The organizing committee for this program
      (alphabetically) is David Atchison, Jay M. Enoch, Vasudevan Lakshminarayanan, and
      Pieter Walraven. Our group of speakers today will follow with discussions of
      aspects of subsequent work which has evolved from the initial discoveries made by
      the late W.S. Stiles and B.H. Crawford.

PMID- 19580115
TI  - Johannes Amos Comenius (1592-1670) and his depiction of lenses and spectacles in
      the first children's picture book.
AB  - Johannes Amos Comenius (1592-1670) was a Moravian clergyman, teacher, and author.
      He is recognized as introducing several concepts of modern education. He advanced
      the views that education should be appropriate to age and development levels and
      that teaching should make use of everyday sensory experience. One of his many
      books, Orbis Pictus, followed those concepts. Orbis Pictus, first published in
      1657, is hailed as the first children's picture book. Among the many commonplace
      objects he included in the book were a mirror, spectacles, a telescope, a
      magnifying lens, and a burning glass.

PMID- 19580116
TI  - Origin of optometry at Cardiff University.

PMID- 19580117
TI  - A comparative study of the social-political determinants of infant and child
      mortality in Sweden and Hungary 1850-1945.

PMID- 19580118
TI  - History of the politics of prostitution in Hungary (19-20th c.).

PMID- 19580119
TI  - [Organizing the prevention of trachoma in Hungary (1884-1903)].
AB  - In Hungary preventative measures against trachoma began in the winter of 1883
      1884. Initially based on the recently issued public health law, it was imbedded
      in a general prevention programme against various epidemics. Local authorities
      and municipal boards were made responsible for carrying it out. These authorities
      and boards were obliged to organize supervision, to establish medical offices and
      ophthalmological wards and to take charge of the continuity of treatments. The
      public health department, however, faced serious difficulties, since most of the
      communities did not have the financial resources for such provision nor did they
      have enough trained physicians. Since the spread of trachoma could not be stopped
      by these measures, a new and effective solution had to be found. A new article
      was created for this purpose, the so called fifth article of the year 1886 "On
      preventing the spread of trachoma", which placed the burden of expenses for
      treatment - in case of lack of means - on the state budget. The government set up
      specialized professional training and the ophthalmological hospital system became
      specialized and modernised with the establishment of special trachoma hospitals,
      or--in public hospitals--ophthalmological wards. Although the first preventative
      measures were taken during the period mentioned above, the disease itself
      persisted, still occurring in large numbers of cases as late as the end of the
      Second World War.

PMID- 19580120
TI  - [Hungarian physicians in exotic lands].

PMID- 19580121
TI  - [The mineral spa of Rudnok as described by staff colonel Henrik Mayer].

PMID- 19580122
TI  - [Contribution to the history of tobacco use].

PMID- 19580123
TI  - [From the physician heros to lifestyle medicine].
AB  - Author sketches the development of medicine in the Greek world from the mythic
      beginnings up to the Corpus Hippocraticum. He emphasizes the importance of the
      presocratic natural philosophy regarding its making. The article derives main
      theories of the so called humoral pathology and those of the ancient dietetics
      also from this heritage.

PMID- 19580124
TI  - [The medical staff of the Austro-Hungarian Navy in World War I].
AB  - The development of the Imperial and Royal Navy of the Austro-Hungarian Empire
      begun in 1868 being based on the structure established by Admiral Wilhelm
      Tegetthoff. The number of staff-doctors of the Navy did not prove enough for the
      needed sanitary measures. The permanent lack of doctors however was compensated
      by the expertise of the medical staff During the WWI, three land hospitals and
      one hospital-ship operated in addition to the doctors working on the single units
      of the fleet In spite of the constant problems, caused by the lack of trained
      doctors the health service of the Imperial and Royal Navy proved to be
      sufficient.

PMID- 19580125
TI  - [The correspondence of Hungarian historians of medicine, Gyula Magyary-Kossa and
      Jeno Pataki. Part II].

PMID- 19580126
TI  - [An unpublished document of a mournful event].

PMID- 19580127
TI  - [The attempt of cardinal Imre Csaky to list the mineral waters of Hungary in
      1718].

PMID- 19580128
TI  - [Has everything been said about the difficult airway? Other points of view are
      possible].

PMID- 19580129
TI  - [Comments on the editorial "Primum non nocere"].

PMID- 19580130
TI  - [Influence of anesthesia and antisepsis on the earliest gynecologic laparotomies:
      historical notes on the bicentennial of the introduction of ovariectomy].
AB  - On the occasion of the bicentennial of the first ovariectomy, we reviewed the
      beginnings of abdominal gynecologic surgery in Spain in order to shed light on
      aspects that are still unclear in medical historiography and that are often
      wrongly presented. We consulted a large number of sources that allowed us to
      follow events in the last quarter of the nineteenth century, discovering
      information we consider definitive and that confirmed our initial hypotheses. The
      work of Dr Federico Rubio, the first to perform an ovariectomy in Spain, is
      highlighted among the early experiences of our Spanish surgeons. Emphasis is
      placed on the high mortality rate associated with this operation at the
      beginning. We also analyze the problems of anesthesia and antisepsis and the
      influence of each on the surgical procedure. The events uncovered were the work
      of a group of forward-thinking surgeons who made considerable progress against
      opposing groups with more conservative views and whose contributions to Spanish
      surgery were far less brilliant.

PMID- 19580132
TI  - [Effect of posture on spinal cord stimulation in patients with chronic pain
      syndromes: analysis of energy requirements in different patient postures].
AB  - BACKGROUND AND OBJECTIVE: Patients being treated with spinal cord stimulation for
      chronic pain complain of variable paresthesias, particularly in relation to
      changes in posture. Such changes affect the great majority of patients with
      implantable pulse generators, requiring them to use the external programmer for
      avoidance of painful paresthesias or even to disconnect the generator, leading to
      loss of pain relief. The aim of this study was to determine the relationship
      between the pulse charge needed for stimulation and the patient's different
      postures. MATERIAL AND METHODS: Observational study of 70 patients treated with
      spinal cord stimulation in the following postures and situations: decubitus
      position, standing, seated, and walking. With the patients standing, we analyzed
      the thresholds of perception, pain, and pain relief, as well as the therapeutic
      range. Studies were performed in all patients. Later, data were analyzed by
      anatomical positioning of the stimulator (cervical, thoracic, sacral, occipital,
      or subcutaneous). RESULTS: In the analysis of the therapeutic range in the
      overall group we identified statistically significant differences between
      decubitus and standing positions and between decubitus position and walking. At
      the level of the thoracic spine differences were identified between all positions
      except between standing and walking and between seated and decubitus positions.
      At the level of the cervical spine, no significant differences were detected.
      Analysis of the pulse charge showed a significant difference in the decubitus
      position, in which less charge was needed to achieve satisfactory stimulation.
      When electrodes implanted at the cervical and thoracic levels were compared,
      differences were found between standing and seated positions (P=.04) but none
      between decubitus position or walking and the other positions. CONCLUSION:
      Stimulation systems are not currently designed to adapt to changes in distance
      between the electrodes and nerve fibers. Improvements are required in this
      respect.

PMID- 19580131
TI  - [Bolus administration of fentanyl vs continuous perfusion of remifentanil for
      control of hemodynamic response to laryngoscopy and orotracheal intubation: a
      randomized double-blind trial].
AB  - OBJECTIVES: To compare the efficacy and safety of fentanyl and remifentanil in
      the prevention of hemodynamic responses to direct laryngoscopy and orotracheal
      intubation, and to compare the effects of these techniques on peripheral blood
      oxyhemoglobin saturation in normotensive women undergoing scheduled gynecologic
      surgery. MATERIAL AND METHODS: Prospective clinical trial in ASA 1-2 patients
      undergoing gynecologic surgery. The patients were randomized to 2 groups: the
      remifentanil group received a perfusion of 1 microg x kg(-1) x min(-1) until
      intubation whereas the fentanyl group received a bolus dose of 2 microg x kg(-1).
      Etomidate (0.3 mg x kg(-1)) and rocuronium bromide (0.6 mg x kg(-1)) were used
      for anesthetic induction. Seven serial measurements of systolic, diastolic, and
      mean arterial pressure were recorded in addition to heart rate and peripheral
      blood oxyhemoglobin saturation at the following times: baseline, denitrogenation,
      postinduction, and 3 more times at consecutive 2-minute intervals. RESULTS: Fifty
      four patients were enrolled. A statistically significant attenuation of the
      postintubation hemodynamic response was observed in the remifentanil group. The
      effect was evident on arterial pressure (P=.0001) and heart rate (P=.031) with
      respect to baseline values. That protective effect was not seen in the fentanyl
      group. No differences in peripheral blood oxyhemoglobin saturation were observed.
      CONCLUSIONS: Remifentanil provides greater hemodynamic control than fentanyl at
      the doses utilized. No adverse effects attributable to these opioids were
      observed in either group.

PMID- 19580133
TI  - [Repercussions and management of perioperative hyperglycemia in cardiac surgery].
AB  - Surgery produces a neuroendocrine stress response that affects resistance to
      insulin, reduces insulin secretion, and increases the release of glucose from the
      liver. This situation can trigger hyperglycemia in both diabetics and
      nondiabetics. Hyperglycemia has been linked to an increase in the morbidity and
      mortality among patients who undergo cardiac surgery, and the benefits of
      correcting hyperglycemia in this setting by means of intensive insulin therapy
      are well documented. This review discusses various aspects of hyperglycemia,
      particularly the evidence supporting stricter control of this condition in
      patients undergoing cardiac surgery. Furthermore, based on the available data and
      recommendations, and our clinical experience, we suggest therapeutic strategies
      to improve the control of hyperglycemia in these patients.

PMID- 19580134
TI  - [Epidural anesthesia in labor and conversion disorder].
AB  - A 37-year-old woman came to our hospital at the beginning of labor. She reported
      a history of depression with attempted suicide some years earlier and had also
      undergone dilation and curettage following an abortion; on admission to our
      hospital, she was euthymic and not receiving treatment. The patient requested
      epidural analgesia. Several hours later, she reported dorsal foot numbness and
      difficulty performing dorsal flexion. After an organic cause had been ruled out,
      a diagnosis of conversion disorder was considered. The incidence of this
      psychiatric disorder is high, though it is usually underdiagnosed. Conversion
      disorder involves at least 1 neurologic symptom suggestive of organic disease.
      Symptoms are not feigned and cannot be ascribed to a medical disease, the effects
      of a toxic substance, or culturally normal behavior, yet there is significant
      clinical, social, and occupational deterioration.

PMID- 19580135
TI  - [Acute myocardial infarction as an incidental finding: reflections on the
      preanesthesia evaluation].
AB  - A preoperative electrocardiogram in a 16-year-old boy scheduled for surgery for a
      fractured radius and mandibular condyle after a motorcycle accident showed signs
      of myocardial ischemia as an incidental finding. Coronary arteriography revealed
      complete occlusion of the anterior descending artery, confirming a diagnosis of
      acute coronary syndrome with ST elevation, with no myocardial viability. As the
      patient's general condition was acceptable, to prevent severe functional
      sequelae, surgery was rescheduled for 17 days later. An axillary block was well
      tolerated at that time. While indiscriminate ordering of preoperative tests is
      not recommended in the literature, such testing continues to be practiced in many
      hospitals, possibly for reasons of organization and legal cover. In our case, the
      electrocardiogram made it possible to diagnose a severe lesion and adjust the
      anesthetic technique to suit this situation, thereby possibly preventing
      devastating consequences. We recommend performing an electrocardiogram on all
      patients with suspected blunt chest trauma, regardless of the severity of the
      lesions, particularly in patients scheduled for surgery.

PMID- 19580136
TI  - [Utility of heliox during treatment of upper airway obstruction secondary to
      bilateral vocal cord paralysis after thyroidectomy].
AB  - Helium is a noble gas whose low density decreases airway resistance. This
      property is utilized when a mixture of helium and oxygen (heliox) is employed in
      certain clinical situations, particularly in the context of airway obstruction.
      We report the case of a woman with severe upper airway obstruction due to
      bilateral vocal cord paralysis after thyroidectomy. Heliox was used temporarily
      to reduce respiratory effort and avoid the need for tracheal intubation while the
      obstruction was being treated with antiinflammatory drugs.

PMID- 19580137
TI  - [Reflections on "Evaluation and management of expected or unexpected difficult
      airways: adopting practice guidelines"].

PMID- 19580138
TI  - [Remarks on the Mallampati-Samsoon test].

PMID- 19580139
TI  - [Vessel perforation after catheterization of the left internal jugular vein].

PMID- 19580140
TI  - [Myxedematous coma in a case of emergency herniorrhaphy].

PMID- 19580141
TI  - [Anesthesia for parathyroidectomy in an elderly patient with dermatomyositis and
      high risk of bronchial aspiration].

PMID- 19580142
TI  - [Neonatal respiratory distress syndrome. Description of an undetected serious
      intraoperative complication].

PMID- 19580143
TI  - [Epidural anesthesia for cesarean section in a woman with a cavernous hemangioma
      of the temporal lobe].

PMID- 19580144
TI  - [Green urine related to infusion of propofol].

PMID- 19580145
TI  - Clinical pathways: the Ottawa Hospital experience.

PMID- 19580146
TI  - Entering long-term care doesn't mean your sexual life is over.

PMID- 19580147
TI  - Nursing in Nunavut.

PMID- 19580148
TI  - One nation under Medicare. Obama must make insurers compete.

PMID- 19580149
TI  - When studies collide. Rethinking the evidence on BPA.

PMID- 19580150
TI  - Don't blame the caveman. Why do we rape, kill and sleep around? The fault, dear
      Darwin, lies not in our ancestors, but in ourselves.

PMID- 19580151
TI  - [Bacterial autoinducing peptides].

PMID- 19580152
TI  - [Cellobiose catabolism by haloalkaliphilic hydrolytic Alkaliflexus imshenetskii].

PMID- 19580153
TI  - [Physiology and biochemistry of alkaliphilic anaerobic hydrolytic bacterium
      Alkaliflexus imshenetskii].

PMID- 19580154
TI  - [Adaptation of lactic acid bacteria to unfavorable growth conditions].

PMID- 19580155
TI  - [The role of thiol redox systems in response of Escherichia coli to distant UV
      irradiation].

PMID- 19580156
TI  - [Cytochromes c of anaerobic methacrylate-reducing Geobacter sulfurreducens AM-1].

PMID- 19580157
TI  - [Polyphosphate consumption and accumulation in Saccharomyces cerevisiae cytosol
      under inactivation of exopolyphosphatase genes PPX1 and PPN1].

PMID- 19580159
TI  - [Antifungal activity of mycocin from Cryptococcus pinus].

PMID- 19580158
TI  - [Biochemical and physiological features of Sinorhizobium meliloti and Sorghum
      bicolor interaction in the presence of phenanthrene].

PMID- 19580160
TI  - [Enhancement of methyl mercury toxicity on Chlorella vulgaris under light and
      cold stress].

PMID- 19580161
TI  - [Characteristics of microspheres formed with bacterial genomic DNA and plasmid
      templates in the process of polymerase chain reaction].

PMID- 19580162
TI  - [Phylogeny of the purple sulfur bacterium Thiocapsa sp. strain BBS on the basis
      of analysis of 16S rRNA, cbbL and nifN and description of new species Thiocapsa
      bogorovii sp.nov].

PMID- 19580163
TI  - [Metabolites of secondary origin as chemotaxonomic markers of fungus genus
      Penicillium isolated from permafrost].

PMID- 19580164
TI  - [Yeasts Candida railenensis from acorns of Quercus robur L].

PMID- 19580165
TI  - [Microorganisms from the digestive tract of the earthworms].

PMID- 19580166
TI  - [Seasonal population dynamic and biodiversity of heterotrophic bacteria from sea
      invertebrates and seawater of the Peter the Great bay, the Sea of Japan].

PMID- 19580167
TI  - [Biotransformation of p-toluic acid by bacterium Rhodococcus ruber P25].

PMID- 19580168
TI  - [The A.E. Kriss centenary (1908-1984)].

PMID- 19580169
TI  - [Model equations for graviosmotic flows in double-membrane system].
AB  - On the basis of Kedem-Katchalsky equations the model equations for graviosmotic
      flows was elaborated. The validity of this model for aqueous glucose solutions
      was verified, using a Kargol's double-membrane cell. In the cell, volume flux was
      measured as a function of time and solution concentrations. These experimental
      findings are interpreted in terms of a gravitational instability that reduced
      concentration boundary layers dimensions. A critical values of concentration
      Rayleigh number for membrane transport is used in a mathematical model for
      gravitationally sensitive volume flows.

PMID- 19580170
TI  - [Microcrystalline cellulose and their flow -- morphological properties
      modifications as an effective excpients in tablet formulation technology
      containing lattice established API and also dry plant extract].
AB  - The production technology of powder cellulose (Arbocel) and microcrystaline
      cellulose (Vivapur) and their application in the composition of direct
      compression tablet mass was provided. The function of silicified microcrystaline
      cellulose type Prosolv in the direct compression process of dry plant extract was
      discussed. An analysis of the chemical structure of cellulose fiber (Vitacel)
      enabled determining its properties and applications in the manufacture of diet
      supplement, pharmaceutical and food products.

PMID- 19580171
TI  - [Starch and its derivatives as excipients in oral and parenteral drug form
      technology].
AB  - The morphological and structural properties of basic types of starch used as
      excipients in solid drug form technology with reference to its bioadhesive
      properties with fully polymer biodegradation. The production technology and
      application of: carboxymethyl starch (CMS), pregelled starch, hydroxyethyl starch
      (HES), hydroxypropyl starch (HPS) and the share of modified starch in technology
      of selected food products is provided. The authors focus on hydroxyethyl starch,
      which is used not only as blood and plasma substitution but also as drug
      camouflage agent in sports competition. In papers were presented based on
      literature data actually used types of starch and their chemical modifications
      products in drug forms and food technology.

PMID- 19580172
TI  - [Synthetic endovascular prostheses in the treatment of the aortic dissection].
AB  - Endovascular technique using endovascular prostheses called stent-grafts offers
      less invasive new method of the aortic dissection. Assessment of endovascular
      aortic dissection type B treatment effectiveness, complications and mortality
      frequency associated with this technique. Among 33 patients (24 men -- 73% and 9
      women -- 27%, aged 19-76 years (average [+/- SD]. Underwent endovascular stent
      grafts implantation procedures using 3 types of grafts: Zenith (2 prostheses --
      13,3%), Talent (11 prostheses -- 73,3%) and Valiant (2 prostheses --13,3%). The
      diameter of proximal end of stent-graft ranged from 34 to 42 mm (mean 37,6 +/-
      3,44 mm), length -- from 130 to 230 mm (mean 183,6 +/- 37,42 mm). Endovascular
      technique is promising strategy of aortic dissection type B treatment. Stent
      graft application faces up to general aspiration to minimize extension and
      traumatization of surgical procedures, to reduce peri- and postoperative
      complications, decrease hospitalization and convalescence period. Endovascular
      technique is the only available method that interferes in the elementary
      mechanism of the aortic dissection pathogenesis. Through the initiation of
      natural repair process (thrombosis of the false lumen), as a result of coverage
      of the primary entry tear, ensures remodeling and stabilization of the aortic
      wall.

PMID- 19580173
TI  - [The use of a synthetic vascular artificial prosthesis or arterial homograft in
      cases of patients with the arteriosclerosis and terminal insufficiency of kidney
      cured by the kidney transplantation].
AB  - Arterial transplantations were practiced in the vascular surgery since the
      beginning of her formation but without successes in the distant observation.
      Transplantation of a kidney is a routine conduct in the treatment of the decadent
      incapacity of a kidney. The dissertation concerns a use of arterial allografts
      kept using a method of a cold ischaemia in the protective liquid or synthetic
      vascular dacron artificial limbs or PTFE used as arterial foot-bridges at
      patients with the atherosclerotic obstruction aortal-pelvic, treated with the
      kidney transplantation. The arterial transplant is created from the aorta,
      arteria iliacas common and externa, femoral arteries common and superficial. A
      tissue material is kept using the method of the cold ischaemia and practical as
      the aortal foot-bridge-femoral or aortal-two-femoral at classified earlier
      patients being subjecteds to transfusion. The other way of a transplantation of a
      kidney at patients with the arteriosclerosis is the realization earlier or one
      temporarily the vascular foot-bridge with use of the synthetic artificial limb.
      It seems that vascular artificial limbs about enlarged resistance on the
      contagion should be used in such a case. Sonographic examinations with duplex
      doppler and angiography are performed in all cases. The analysis of such cures
      can make a creation of the most profitable algorithm of the conduct possible in
      cases of patients suffering from ischaemia of lower limbs and requiring a
      transplantation of a kidney because of its incapacity.

PMID- 19580174
TI  - [The usage of synthol in the body building].
AB  - Synthol consists usually of oil, benzyl alcohol and lidocain. It consists of 85%
      of oil (normally it is oil built by medium-length MTC chains because it gives the
      best effects), 7,5% of lidocain (painkiller), 7,5% of alcohol (to sterilize the
      mixture). Synthol is a substance used by body builders as a temporary implant
      which is injected deeply into the muscle. The enlargement effects are immediate.
      Synthol is used in small groups of muscles to enlarge their volume (for example
      triceps, biceps, deltoids, muscles of the calf). Some serious drawbacks can be
      visible while using synthol. The muscles deform and become unnaturally shaped.
      The side effects of synthol are manifold and they can also cause a damage of
      nerves, oil embolic of the pulmonary, occlusion of the pulmonary artery,
      myocardial infarction, cerebral stroke and infectious complications.

PMID- 19580175
TI  - Diathermy training and usage trends among surgical trainees--will we get our
      fingers burnt?
AB  - INTRODUCTION: We aimed to assess the current trends in diathermy use as well as
      the presence or absence of formal diathermy training amongst higher surgical
      trainees (HSTs) in the UK. MATERIALS AND METHODS: A national e-mail survey was
      implemented, contacting 300 randomly selected HSTs in general surgery. A
      questionnaire was used to ascertain their current practice and the presence or
      absence of formal diathermy training. RESULTS: Overall 126 (42%) HSTs across all
      levels of training and subspecialty interests responded. Only 50.8% stated they
      had received formal diathermy training whereas 49.2% had no formal training.
      Diathermy is used by 23.8% of responders for laparotomy skin incisions, while
      76.2% use a scalpel. For colonic mobilisation, 49.2% use diathermy and 50.8%
      scissors. For rectal mobilisation 55.5% use diathermy, 42.9% scissors and 1.6% a
      harmonic scalpel. Nearly 90% of responders do not place diathermy pads on the
      patient themselves, 68.3% do not routinely check diathermy equipment before use
      and 66.7% do not check the diathermy pad site at the end of the operation. Only
      80.9% stated that a diathermy complication is the surgeon's responsibility, while
      the remaining 19.1% would blame the scrub nurse, circulating nurse, operating
      department assistant (ODA), manufacturer or a combination of the above.
      CONCLUSION: Nearly half of HSTs in this study did not receive any training in the
      use of diathermy, resulting in failure to adhere to what is considered best
      practice. This may lead to adverse events for the patient along with medico-legal
      consequences. This problem could be overcome by ensuring HSTs receive adequate
      formal diathermy training and we suggest that a dedicated diathermy course is
      incorporated in basic surgical training curricula.

PMID- 19580176
TI  - Fournier's gangrene: a dreadful disease.
AB  - BACKGROUND: Although there is much consensus, certain controversies still exist
      regarding the pathology of Fournier's gangrene. The purpose of this study was to
      determine the prevalence of the disease in the catchment area of the three
      teaching hospitals, to identify the systemic predisposing factors and local
      aetiological factors, and to assess the recommended role of aggressive surgical
      debridement as a part of treatment. MATERIALS AND METHODS: This prospective study
      was conducted in the surgical departments of three tertiary care hospitals of the
      Khyber Medical University, Peshawar, Pakistan, from 1 January 2002 to 30 June
      2007. Detailed history and examination of all patients were carried out to reach
      the diagnosis of Fournier's gangrene. After initial resuscitation, patients were
      treated aggressively, including surgical debridement. RESULTS: Sixty patients
      were studied in the study period. The male to female ratio was 5:1. The age range
      was 20-75 years with mean 47+17.4 (SD) years. The socioeconomic status of
      patients was poor (the average income was less than $50 per week) in 36 (60%) and
      24 (40%) were middle class (the average income being $50-100 per week). Thirty
      nine patients (65%) presented in the hot humid months of the year. Extent of the
      disease was scrotum in 18 patients (30%), perineum in 30 (50%) and abdominal wall
      in 12 (20%). Systemic predisposing factors identified in our study were diabetes
      mellitus in 20 (33.33%) patients, chronic alcohol abuse in two (3.33%) and long
      standing steroid therapy in four (6.67%) while in 34 patients (56.67%) no cause
      was identified. The local aetiological origin of Fournier's gangrene was
      urogenital in 14 (23.33%) patients, anorectal in 10 (16.67%) and cutaneous in 8
      (13.33%) and no local pathologies could be identified in 28 (46.67%) patients.
      The mean time interval between first symptom and initial treatment was 2.5 days
      with a range of 1-7 days. Number of debridement sessions per patient was 2-6
      (mean, 3.15). Mean hospital stay was 31+7 (SD) with a range of 10-50 days.
      Morbidity was 80%. Four patients (6.67%) died. Three of these patients presented
      to hospital 5-6 days too late. CONCLUSION: Fournier's gangrene is not an uncommon
      disease in South Asia. Systemic predisposition such as diabetes mellitus, long
      standing steroid therapy, chronic alcoholism and even the hot humid season can
      contribute to this dreadful disease. Local causes in the form of urogenital,
      anorectal and cutaneous disorders may trigger this disease in some patients.
      Early recognition of disease and aggressive surgical debridement are the main
      treatments.

PMID- 19580177
TI  - Is intravenous urography necessary in the assessment of renal duplex system in
      children?
AB  - OBJECTIVE: Partial or complete duplication of the renal tract may be an
      incidental finding or may be associated with significant pathology. Accurate
      assessment is not always easy. This retrospective review was undertaken to
      determine whether intravenous urography (IVU) in combination with a DMSA renal
      scan provides significant additional information. PATIENTS AND METHODS: Eighteen
      patients referred to our imaging department with a provisional diagnosis on
      ultrasound of renal tract duplication during a three year period were identified
      by searching the radiological computer files. The presenting features were
      urinary infection (13), abdominal pain (3) and abnormal antenatal sonography (2).
      RESULTS: Four patients were found not to have renal duplication. There was
      concordance between the IVU and DMSA scan in seven. Additional clinically
      relevant information was obtained in three cases. A false negative result from
      the DMSA scan was found in four children and a false positive result in three.
      CONCLUSION: In a significant number of cases of possible renal tract duplication,
      additional relevant information can be obtained from an IVU. Patient distress is
      minimised by combining the IVU and DMSA in one single episode of venous access.
      Review of the radiological images during the investigation allows minimisation of
      radiation dosage.

PMID- 19580178
TI  - Is it safe to omit radiotherapy following wide local excision for ductal
      carcinoma in situ?
AB  - BACKGROUND: Debate regarding the use of radiotherapy (RT) after breast conserving
      surgery is currently one of the most controversial areas in breast cancer
      management. In our centre we prefer to avoid RT, which is not without its own
      risks, as a primary treatment modality in the majority of cases of ductal
      carcinoma in situ (DCIS) that are amenable to wide local excision. METHODOLOGY:
      Prospectively entered data were reviewed for all patients (n=100) that underwent
      breast conserving surgery for DCIS by the senior author over a ten year period.
      Kaplan-Meier survival curves were calculated for the total sample and for a
      series of univariate analyses. RESULTS: The mean follow-up for this sample was 50
      months. The overall rate of recurrence was 6%, one-third of which were invasive.
      The estimated eight year disease free survival was 91.6%. CONCLUSIONS: In this
      group of patients outcome has not been affected by radiation therapy, hormone
      manipulation or chemotherapy. It has therefore enabled us to assess recurrence
      rates free of any potentially confounding treatment related influences. The
      results from this study suggest, that in our hands, the recurrence rates for DCIS
      following wide local excision alone are similar to those reported in series in
      which radiotherapy was used as adjuvant treatment.

PMID- 19580179
TI  - Current concepts in the management of complex elbow trauma.
AB  - Complex instability of the elbow, also known as fracture dislocation of the
      elbow, is one of the most challenging injuries of the musculoskeletal system. A
      clear understanding of the biomechanics of the joint with special focus on the
      relative contributions of the articular components and the ligamentous
      constraints is critical to the proper management of these injuries. The accurate
      recognition and implications of associated injuries offers a rationale for
      approaching these difficult problems by appropriately addressing the elements of
      the trauma. Further, doing so in a timely fashion enhances the outcome.
      Currently, even the most devastating of injuries are felt to have a more
      favourable prognosis than was present in the past if the principles contained
      herein are followed.

PMID- 19580180
TI  - Rectal cancer.
AB  - Surgery is the cornerstone of rectal cancer treatment. Oncological cure and
      overall survival continue to be the main goals, but sparing of the anal sphincter
      mechanism and functional results are also important. The modern management of
      rectal cancer is a multidisciplinary approach, and pre-operative staging is of
      crucial importance when planning treatment in these patients. Pre-operative
      staging is used to determine the indication for neoadjuvant therapy prior to
      surgical resection or to determine whether local excision is an option in
      carefully selected patients with early rectal cancer. Surgery in the form of
      total mesorectal excision (TME) has become the standard of care for mid and
      distal rectal cancers. Early rectal cancers do not require neoadjuvant therapy.
      For locally advanced cancers of the lower two-thirds of the rectum, the
      combination of surgical resection with chemoradiotherapy decreases local
      recurrence rates and probably improves overall survival. Whereas in the past
      local excision was only contemplated in patients who were unfit for radical
      surgery or for local palliation in cases of metastatic disease, over the last
      number of years there has been increasing interest in local treatment with
      curative intent in early rectal cancer.

PMID- 19580181
TI  - Evolving issues in the prevention of surgical site infections.
AB  - Surgical site infection is one of the more common causes of post-operative
      morbidity. Such infections contribute to prolonged recovery, delayed discharge
      and increasing costs to both patients and the health service. In the current
      climate increased emphasis is being placed on minimising the risks of acquiring
      or transmitting these nosocomial infections. This article reviews the current
      literature obtained from a Pubmed database search in relation to three specific
      aspects of surgical site infection: compliance with prophylactic antibiotics,
      post-discharge surveillance and novel methods for preventing surgical site
      infections. These topics represent areas where many institutions will find room
      for improvement in the prevention of surgical site infections. Tight adherence to
      prophylactic antibiotic guidelines, close followup of surgical wounds during and
      after hospital discharge, and attention to oxygenation status and the body
      temperature of patients may all prove to be useful adjuncts in significantly
      decreasing surgical site infections.

PMID- 19580182
TI  - COX-2, VEGF and tumour angiogenesis.
AB  - Epidemiological evidence suggests a protective effective of regular NSAID use
      against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated
      in many cancers and has been associated with increased VEGF production and
      angiogenesis. Angiogenesis is the formation of new vessels from existing
      vasculature and as an essential process for tumour development represents an
      important therapeutic target. Following an extensive review of the literature
      this article details the current knowledge on the role of COX-2 in tumorigenesis
      focusing on its relationship to angiogenesis and VEGF production by tumour cells.
      While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial
      effect, the possibility of COX-2 independent effects being partly or wholly
      responsible for this benefit cannot be excluded.

PMID- 19580183
TI  - Endovenous therapy of varicose veins: a better outcome than standard surgery?
AB  - In the UK approximately one million people are affected with varicose veins.
      Nearly half a million patients seek advice from their GPs about lower limb
      varicose veins related symptoms every year. Therefore, they constitute an
      important part of the elective operations and waiting lists in NHS hospitals.
      About 40,000 operations for varicose veins were performed in the NHS in 2001. The
      majority (60-70%) of those patients had an incompetent saphenofemoral junction
      (SFJ) and great saphenous vein (GSV) reflux. The traditional and most common
      approach for treating SFJ incompetence and GSV reflux is saphenofemoral
      disconnection and GSV stripping to the knee. Despite being considered a minor
      surgical procedure, complications are not uncommon. The minimally invasive
      endovenous treatment of lower limb's varicose veins has been used over the last
      few years in many centres across the world. It would appear to be equal to, if
      not superior to, traditional surgery. It has also been proven to be safe with few
      serious complications. The most common treatments are endovenous laser ablation
      and endovenous radiofrequency ablation and chemical sclerotherapy. The case for
      minimally invasive strategies appears to have been accepted by many patients
      already and it would appear in trials that they are 'voting with their feet'.
      Rigorous scientific evidence remains elusive and not yet conclusive. As in all
      other branches of surgery new technology should be embraced but cautiously, with
      all results collected and disseminated to finally prove the utility or otherwise
      of this technique.

PMID- 19580184
TI  - Re: Bhattacharya D, Caird J D, Choudhari K A. Mashed-muscle and oxidised
      regenerated cellulose (Surgicel) hammock: a quick and effective way to repair
      frontal air sinus. Surgeon 2008; 6 (6): 341-3.

PMID- 19580185
TI  - Re: Westwood K et al. Incentive spirometry decreases respiratory complications
      following major abdominal surgeries. Surgeon 2007; 5 (6): 339-42.

PMID- 19580186
TI  - [Program of early nephro-urologic management of children with congenital
      hydronephrosis].
AB  - Congenital anomalies of kidney and urinary tract (CAKUT) are the main cause of
      end stage renal disease in childhood. Early prenatal detection with planned
      postnatal diagnosis and therapy are the mainstay of management of neonates with
      CAKUT which is aimed at the conservation of renal tissue. The above assumptions
      led to the establishment of the Pommeranian Program for Management of Children
      with CAKUT. The strategy of the program is to coordinate prenatal diagnosis
      performed by obstetricians, postnatal care by neonatologists and early management
      by pediatric nephrologists and urologists. It will involve approximately 200
      neonates annually. The basic concept of the program includes the following: 1.
      Delivery of a child with congenital hydronephrosis detected prenatal should take
      place in a center with specialist neonatal care. 2. Child with a congenital
      hydronephrosis should remain under specialist nephro-urologic care immediately
      after delivery. 3. Child with a congenital hydronephrosis should be qualified to
      scheduled urologic surgery after results of diagnostic tests and according to
      general status. 4. Model of integrated care on a child with congenital
      hydronephrosis should consist in close cooperation between obstetricians,
      neonatologists, pediatric nephrologists, and urologists.

PMID- 19580187
TI  - [The influence of hemodialysis on heart's intraventricular conduction system-
      pilot study].
AB  - The highest percent of cardiac muscle damages is written down in children which
      are exposed to hemodialysis. In this group the heart examinations using body
      surface heart potential mapping (BSPM) method have been carried out. The aim of
      the study was to assess the influence of hemodialysis on heart's electrodynamics
      in children and adolescent during replacement therapy. MATERIAL AND METHODS:
      Multielectrode recording have been done in every kid before and after
      hemodialysis. For every record it was created isopotential map. By the comparing
      our maps with model maps for healthy children it was affirmed that in greater
      part of studied examples of hemodialysed children there are present early changes
      indicating conducting disturbances in left bundle of fasciculus
      atrioventricularis (His) and initial stage of left ventricular hypertrophy (LVH).
      That changes haven't been confirmed in classic ECG, which suggests that the
      disturbances in excitation conductance observed on isointegral maps are far
      beyond the area detected by 12-electrode classic ECG recording. RESULTS: The maps
      made before dialysis are characterised by large, unsymmetrical isopotential lines
      changes over the left and right ventricle. After carried out of hemodialysis the
      image of ECG records was improving. In all of cases the isoline distribution in
      sternal and anterior lower left part of chest comes back to norm. Changes are
      visible merely over the left ventricle and in anterior upper right part of chest
      what is connected with just stabilised conducting disturbances in the left branch
      of His bundle, left bundle of fasciculus atrioventricularis (His bundle).
      CONCLUSIONS: 1. In children who are treated by repeated hemodialysis approach to
      disturbances in the cardiac intraventricular conduction system. 2. Those
      disturbances are improved by a singular hemodialysis. 3. BSPM method detects
      earlier changes in the cardiac intraventricular conduction system than the
      classical ECG.

PMID- 19580188
TI  - [Pulse pressure and circadian blood pressure profile in children with IgA
      nephropathy and Shoenlein-Henoch nephropathy].
AB  - Elevated pulse pressure and disturbed circadian blood pressure profile are risk
      factors for organ damage of arterial hypertension. The aim of the study was to
      evaluate of prevalence of elevated pulse pressure and disturbed circadian blood
      pressure profile in children with IgA nephropathy (IgAN) and Schoenlein-Henoch
      nephropathy (SHN). MATERIAL AND METHODS: 48 children (27 males and 21 females)
      with IgAN (n=21) and SHN (n=27) aged from 4.5 to 19 mean 13.3 years were enrolled
      into the study. In all patients ambulatory blood pressure monitoring (ABPM) was
      performed. In detail pulse pressure during 24 hours, activity and rest period
      (PP/24 h, PP/a, PP/r) as index PP (PPI) and circadian blood pressure profile were
      analyzed. In all patients BMI Z-score, hypertensive medications, GFR according to
      Schwartz formula and serum uric acid level were evaluated. RESULTS: Elevated
      pulse pressure was found in 17 (35.42%) patients: in 11 with SHN and in 6 with
      IgAN. In patients without antihypertensive treatment (n=18) positive correlations
      between PPI/24 h, PPI/a and serum uric acid level (r=0.59; r=0.48; p<0.05
      respectively) and between PPI/24, PPI/a and BMI-Z score (r=0.57; r=0.50; p<0.05
      respectively) were demonstrated. Disturbed circadian blood pressure profile was
      found in 13 (27.1%) patients; 11 patients with disturbed blood pressure profile
      did not have hypertension in ABPM. 6 patients had disturbed blood pressure
      profile despite antihypertensive treatment. Kidney function was normal in all
      patients. CONCLUSIONS: Disturbed circadian blood pressure profile is a common
      phenomenon in children with IgAN and SHN also in normotensive patients and in
      patients on antihypertensive treatment. Elevated uric acid serum level may be a
      marker of elevated pulse pressure in children with IgAN and SHN.

PMID- 19580189
TI  - [Osteopontin, platelet-derived growth factor and bone morphogenetic protein-7 in
      children with chronic kidney disease on renal replacement therapy--preliminary
      results].
AB  - Cardiovascular complications are associated with CKD and tend to aggravate in the
      course of dialysis. The disturbed calcium-phosphate metabolism plays the crucial
      role in the progression of atherosclerosis. Among the new, possible factors,
      taking part in this process, there are the calcification inhibitors: OPN and BMP
      7, and the calcification process promoter:PDGF-BB. The aim of the study was to
      assess the concentrations of the above mentioned factors in the dialysis
      patients, comparing the two types of therapy: peritoneal dialysis (PD) and
      hemodialysis (HD). MATERIAL AND METHODS: OPN, PDGF-BB and BMP-7 plasma
      concentrations were assessed by ELISA, in 16 children on PD, in 13 on HD and in
      12 controls with normal kidney function. RESULTS: OPN concentrations were higher
      in HD patients, whereas in PD patients comparable to those in the control group.
      There were no differences between PD and HD children. PDGF-BB median values were
      lower in both dialysis groups than in the controls, and the lowest of them were
      observed in HD patients. BMP-7 concentrations were increased in dialysis
      patients, comparing to the control group, and higher in HD patients than in the
      PD ones. CONCLUSIONS: Disturbed concentrations of OPN, PDGF-BB and BMP-7 in
      dialysis patients may indicate that the preventive mechanisms against the
      calcification disorders have been set. The fact that the changes in the
      concentrations of the above mentioned factors are less pronounced in the PD
      group, lets us assume that PD is the type of dialysis that interferes to the
      lesser extent with the balance between the promoters and inhibitors of
      calcification.

PMID- 19580191
TI  - [Homocysteine and glutathione metabolism in steroid-treated relapse of idiopathic
      nephrotic syndrome].
AB  - Changes in metabolism of aminothiols may have an influence on endothelial
      function or change the red-ox balance. The aim of study was designed to assess
      changes in plasma aminothiols': proatherogenic (homocysteine-HCY) and
      antiatherogenic (glutathione-GSH) metabolism in nephrotic syndrome in children.
      MATERIAL AND METHODS: The study group included 77 nephrotic children (aged 2-18
      years) divided into four groups, i.e. in acute phase of the disease (24), during
      steroid-induced (24), steroid-free (12) and in long-term remission (17). Twenty
      five healthy children served as controls. GSH and HCY in plasma were assessed by
      high-performance liquid chromatography. Fraction of protein-bound and free
      aminothiols was assessed and albumin saturation was calculated. RESULTS: GSH and
      its fractions' concentrations were comparable to healthy subject, however in
      early relapse free fraction was significantly higher than in late remission. The
      albumin saturation with GSH was significantly higher in early than in late
      relapse. Total HCY concentration was decreased in early relapse, elevated after 2
      week and comparable to controls after 8 week of treatment. HCY free fraction and
      albumin saturation were elevated within first 2 weeks. Children in long-term
      remission showed elevated total concentration of HCY and GSH and their protein
      bound fractions when compared to controls. Albumin saturation with these
      aminoacids was higher as well. CONCLUSION: The study showed aminothiol imbalance
      in children in first weeks of relapse of nephrotic syndrome.

PMID- 19580192
TI  - [Serum adiponectin and resistin level in children with idiopathic nephrotic
      syndrome].
AB  - The adipose tissue was recognized as an active endocrine organ. The adipopkines
      seem to play an important role in the modulation of inflammatory response and
      have a pleiotropic function. The aim of this study was to evaluate serum resistin
      and adiponectin level in children with idiopathic nephrotic syndrome (INS).
      MATERIALS AND METHODS: 39 children with INS aged 2.5-17 year (mean 9.35 +/- 5.6),
      15 children in relapse, 24 in remission and 8 healthy were included into the
      study. Serum total protein, albumin, cholesterol, daily proteinuria and BMI were
      measured in children with INS. Serum resistin and adiponectin levels were
      determined by ELISA. RESULTS: Increased resistin and adiponectin levels were
      observed during relapse and remission of INS, compared to controls. No
      significant difference between adipocytokines in relapse and remission INS was
      found. Serum resistin level decreased in remission of INS, compared to relapse,
      but the value did not reach statistical significance. Between resistin and
      cholesterol, resistin and proteinuria positive correlation was found. Negative
      correlation between resistin and serum albumin was observed. CONCLUSION:
      Increased serum level of resistin and adiponectin was observed in children with
      relapse of INS or in early phase of remission. These finding suggests that they
      may play a role in the pathogenesis of INS in children. It requires further
      investigation based on a broad study.

PMID- 19580190
TI  - [Matrix metalloproteinases and their tissue inhibitors in children and young
      adults on chronic hemodialysis--preliminary results].
AB  - The proteolytic system of MMPs and TIMPs may play an essential role in vascular
      remodeling and atherosclerosis, but the data concerning such influence in the
      patients on chronic hemodialysis are scarce. The aim of the study was to assess
      the concentrations of selected MMPs and their inhibitors in the patients
      hemodialyzed on the polysulfone membranes. MATERIAL AND METHODS: 11 children and
      young adults on chronic HD were enrolled in the study, 15 age-matched subjects
      with normal kidney function served as controls. The serum concentrations of MMP
      2, MMP-9, TIMP-1 and TIMP-2 were assessed by ELISA. RESULTS: The median values of
      all MMPs and TIMPs were elevated in patients before HD vs. controls (p<0.0001)
      and decreased after a single HD session (p<0.01), yet remained higher than in the
      control group (p<0.001). The MMP-2/TIMP-2 ratio was decreased vs. controls both
      before and after a HD session (p<0.0001). Contrarily, the MMP-9/TIMP-1 ratio
      before HD was higher than in controls (p<0.05), but after HD dropped to the
      values lower than those in the control subjects (p<0.01). CONCLUSIONS: The
      increased concentrations of all parameters may indicate the proteolytic
      overactivity in the examined population. A single polysulfone HD session tends to
      deepen the MMPs/TIMPs dysfunction, although this impact seems transient.

PMID- 19580193
TI  - [Glomerulopathies as causes of end-stage renal disease in children].
AB  - The aim of the study was assessment of the frequency of glomerular diseases (GD)
      as a cause of end-stage renal disease (ESRD) in children. PATIENTS AND METHODS:
      Retrospectively, causes of ESRD, frequency, duration of the disease until
      diagnosis of ESRD in 195 children treated in 1973-2008 were analysed. RESULTS:
      Among children with ESRD, GD were diagnosed in 94 (48.2%)--mean age 10.9 +/- 4.3
      years, congenital abnormalities of urinary tract in 61 (31.2%) aged 10.6 +/- 4.3
      years and other causes in 40 (20.5%). Among 94 children with GD the 49 (52%)
      patients had primary glomerulonephritis (GN): 24--crescentic GN, 9--focal
      segmental glomerulosclerosis, 8--mesangioproliferative GN, 5--IgA nephropathy, 3-
      membranoproliferative GN. In 37 (39.5%) the causes of ESRD were secondary
      glomerulopathies: 20--amyloidosis, 10--hemolytic-uremic syndrome, 6--Schonlein
      Henoch nephropathy, 1--Wegener granulomatosis. In 8 (8.5%) patients causes of
      ESRD were: Alport syndrome in 2, congenital nephrotic syndrome in 1 and in 5 type
      of glomerulopathy was unknown. Time between diagnosis of nephropathy and start of
      dialysis was 0-13.75 years, median 1.1 in patients with GD and was significantly
      shorter (p<0.003) than this time in the group with congenital abnormalities of
      the urinary tract (0-14.9 years; median 3.83). There was no difference between
      primary GN and secondary glomerulopathies. CONCLUSIONS: Chronic glomerulopathies
      were the most frequent cause of ESRD in investigated group. Time between
      diagnosis of chronic renal disease and initiation of renal replacement therapy
      was significantly shorter in children with glomerulopathies than with congenital
      abnormalities of urinary tract.

PMID- 19580195
TI  - [Chronic dialysis patients' expectations towards dialysis nurses].
AB  - As a result of changes in the Polish healthcare system, healthcare institutions-
      including dialysis units--are expected to provide their patients with broad
      spectrum and high-quality services. Nurses are the members of the therapeutic
      team who spend most time with the patient undergoing renal replacement therapy,
      and thus the image of the whole dialysis unit depends on their work. The aim of
      the study was to assess the dialysis patients' expectations towards their nurses.
      MATERIAL AND METHODS: The study group consisted of 150 adult dialysis patients
      treated with hemodialysis in dialysis units in Lodz region. The participants were
      asked to fill out an anonymous questionnaire specially tailored for the study.
      RESULTS: We showed that dialysis patients were generally satisfied with the level
      of care provided by nurses and described them as reliable, professional and well
      qualified. Patients especially valued kind attitude, smile and friendliness of
      the nurses. Fully professional care was noticed by 25.7% of patients. Patients
      dialyzed for a longer period of time (over 10 years) described nurses' knowledge,
      practical skills and independence with more criticism. A quarter of them stated
      that nurses always relied on the doctor's decision. CONCLUSIONS: The study
      revealed that dialysis nurses' work, practical skills and attitude were assessed
      very well by patients. Their level of satisfaction would be higher if nurses
      spent more time and initiated more discussion with the patients. The high merit
      that nurses received should be considered as a stimulus that ought to increase
      the professional independence and quality of dialysis nurses performance.

PMID- 19580194
TI  - [Independence of nurses in the therapeutic team based on dialysis units in region
      of Lodz].
AB  - Professional role of modern nurse requires from her in process of treatment this
      kind of procedure, which is expected by patient and it is implicated with
      direction of medical operation. Dependence place of doctor occupies then sense of
      cooperation. Insufficient independence, making oppositions before decision-making
      and fear before personal responsibility causes, that doctors and patients don't
      feel comfort of cooperation, what is effective lack of confidence. The aim of
      research was finding the answer for questions: How is formed nursing independence
      by taking care of patients in peritoneal dialysis? What is level of nurses
      preparation for independent work in dialyses stations? Has education of nurses
      really influence on quality of professional care? MATERIAL AND METHODS: Presented
      work is based on questionnaire research, carried out from December 2006 to March
      2007. It has included 82 nurses, who working in dialyses stations in Lodz
      province. RESULTS: Research has exerted, that over 3/5 respondents haven't been
      sufficiently prepared to work in dialysis station. About 30% of researched group
      didn't have enough knowledge to embrace patients entire care. The will of
      uplifting of professional qualifications have had 78% nurses. Respondents
      thought, that nursing group only partially (42%) should take independent
      operations. Only 50% nurses have conceded, that they have possibility to obtain
      the full information about health status of patients from doctors. CONCLUSIONS:
      Nursing independence in conduct of patients therapy in peritoneal dialysis isn't
      high. Systematic training and longest professional practice in dialysis station
      should help farthest development of nursing independence.

PMID- 19580196
TI  - [Urinary laminin and fibronectin level in children with nephritic syndrome].
AB  - Laminin (LN) and fibronectin (FN) are important extra cellular matrix (ECM)
      proteins. Disturbance between production and degradation of ECM proteins
      contributes to renal scarring. The aim of the study was evaluation the levels of
      urinary LN and FN in children with proteinuria in nephrotic syndrome (NS).
      MATERIALS AND METHODS: Examinations were conducted on 71 children, 3-15 years
      old: (A)--44 children with NS (proteinuria above 50 mg/kg b.v./24 hours); (B)--27
      children without proteinuria (remission NS). Control group (K)--30 healthy
      children. Concentration of LN and FN were determined by EIA. RESULTS: In urine of
      children with NS (A) urinary concentration of LN significantly increased, in
      comparison to control (K) (p<0.05), but FN was normal (p>0.05). In children with
      remission of NS (B) urinary concentration of LN was unchanged (p>0.05), but
      concentration of FN significantly decreased (p<0.05). In renal biopsies majority
      children of A group presented minimal changes, but majority children of B group
      presented hyalinization of renal tubules. CONCLUSION: Nephrotic proteinuria
      disturbs production of LN and increases its urinary excretion, but did not
      influence on urinary excretion of FN.

PMID- 19580197
TI  - [The use of sevelamer in the treatment of resistant hyperphosphataemia in
      children with chronic renal disease].
AB  - The aim of study was the estimation of efficacy and safety of sevelamer treatment
      in children with chronic kidney disease with resistant hyperphsphatemia. MATERIAL
      AND METHODS: The study group was 7 patients (hemodialysed--2 boys, mean age 7,
      7+/-0.1; peritoneal dialysis--5: 3 boys and 2 girls, mean age 5, 6+/-5.0).
      Sevelamer (Renagel, 800 mg, Genzyme) was used in all patients in mean dosis of
      117 mg/kgm.c./d due to lack of effect of the typical treatment (vitamin D, diet,
      calcium carbonate). Results of treatment by sevelamer were estimated by measuring
      of calcium, phosphates, albumins, parathormone and alkalic phosphate
      concentration in the serum and blood gases after 6 and 12 month. RESULTS: There
      were found that sevelamer treatment significantly decrease the phosphates
      concentration and CaxP product in the serum without influence on concentration of
      PTH or calcium. Any adverse events were observed during the study and any drug
      intolerance. CONCLUSION: Sevelamer treatment may be usefulness in children with
      resistant hyperphosphatemia.

PMID- 19580199
TI  - [Pyelonephritis with massive renal tissue necrosis in child with urinary tract
      malformation--a case report].
AB  - The aim of the case report is presentation of unusual and heavy clinical course
      of pyelonephritis with renal tissue necrosis in a child with urinary tract
      malformation. Nine month old girl was admitted to hospital in heavy clinical
      status due to pyelonephritis--urosepsis. It was complicated by acute renal
      insufficiency. Patient was treated by broad-spectrum antibiotics and parenteral
      nutrition. She was feverish for 14 days. Computed tomography done in order to
      exclude abdominal abscess showed massive renal tissue necrosis of on both sides.
      Antibiotic treatment was successful after 6 weeks. Urological evaluation revealed
      bilateral vesico-ureteral refluxes grade IV. Scintigraphy showed multiple scars.
      Patient was treated Deflux injections (twice). We noted 5 urinary tract
      recurrences despite antibiotic profilaxis. GFR of 75 ml/min/1.73 m2 was estimated
      at age of 16 m. Immunodeficiency or malignancy as background of clinical course
      were excluded. The case we describe presents severe clinical course of
      pyelonephritis due to complex urinary tract malformation that is to be considered
      despite based on modern publications "sparing" strategies of diagnosis and
      profilaxis in urinary tract malformations.

PMID- 19580198
TI  - [Preliminary results of a program for the early management of children with
      congenital hydronephrosis].
AB  - Antenatal hydronephrosis is one of the most frequently diagnosed congenital
      abnormalities in the fetus. The aim of the study is to present the preliminary
      results of a newly launched Pommeranian Program for Early Management of CAKUT in
      Children. MATERIAL AND METHODS: 105 neonates and infants with hydronephrosis were
      assessed between Jan and Dec 2007 (27 girls and 78 boys). All patients had
      postnatal ultrasound performed. Static and dynamic scyntigraphy and cystography
      were performed according to set indications. Therapeutic decisions were made
      following a team meeting between pediatric nephrologists and urologists. RESULTS:
      56.2% of children with hydronephrosis had documented prenatal findings: 61%-
      pyelectasis, 15.3% renal cysts, 5.1% unspecified renal pathology, in 18.6% no
      renal pathology. 82.6% of newborns had term births but perinatal complications
      were observed in 30.5%. Initial postnatal diagnosis was performed by neonatal
      wards in 22.8% newborns and by the children's pediatrician in 31.4% of infants.
      Following referral to nephro-urology centre cystography was performed in 22.9% of
      infants and scintigraphy in 36.2%. 21.9% of infants were qualified for surgical
      intervention at an average age of 24 + 13 weeks. CONCLUSIONS: 1. Only half of the
      children with congenital hydronephrosis are to nephro-urology care following
      prenatal diagnosis. 2. A large number of perinatal complications are observed in
      newborns with prenatally diagnosed hydronephrosis. 3. The management of newborn
      hydronephrosis requires better cooperation between obstetricians, neonatologists,
      pediatric nephrologists and urologists.

PMID- 19580200
TI  - [Peritonitis in the course of peritoneal dialisis caused by Haemophilus
      influenzae with BLNAR phenotype].
AB  - Most common bacterial species causing peritonitis in the course of peritoneal
      dialysis (PDP) are coagulase-negative staphylococci, Staphylococcus aureus and
      streptococci. Haemophilus influenzae is rarely associated with PDP. Hereby we
      present the first known case of APD-associated peritonitis caused by non-type
      able H. influenzae (NTHi) presenting the beta-lactamase negative, ampicillin
      resistant (BLNAR) phenotype. An 18 year old boy who had been treated with the APD
      for 12 months due to SLE was admitted in good general condition with diagnosis of
      PDP. Standard diagnostic and therapeutical procedures were initiated. Dialysis
      fluid was turbid with cytosis of 435 WBC/ml. From dialysis fluid pure culture of
      Gram-negative coccobacillus was isolated. The isolate was identified as a BLNAR
      phenotype. The same bacterium was isolated from nasal swab. Blood cultures were
      negative. After evaluation of antimicrobial susceptibility the treatment was
      changed for the oral ciprofloxacin. The treatment was successful. Control tests 2
      days later revealed cytosis of 15 WBC/mm3 and control cultures of peritoneal
      fluid were negative. After two weeks of treatment the patient was discharged in a
      good condition. Haemophilus influenzae is a bacterium frequently colonizing the
      nasopharyngeal cavity. A PCR-based method allowed to classify isolates as NTHi.
      Infection was probably of the respiratory origin as the isolates (from peritoneal
      fluid and nasal swab) were undistinguishable. There are only few reports
      describing this species as an ethiologic agent of peritonitis. This case prove
      that Haemophilus species should be taken into account as a possible aethiologic
      agent of PDP, especially in patients on immunosupression with carrier state of H.
      influenzae in the upper respiratory tract. This kind of microorganism requires
      specific conditions during its growing in vitro. Identification of its
      sensitivity to antibiotics is essential in order to detect strains of BLNAR
      phenotype, as it is a crucial part of an effective antibiotic therapy.

PMID- 19580201
TI  - [Major renal biopsy complications in 11-year-old boy--a case report].
AB  - Renal biopsy is an essential procedure in the diagnosis, treatment and follow-up
      of renal diseases. The risks associated with performing percutaneous renal biopsy
      have substantially decreased in the past decades. However, major complications
      still occur. We report and discuss a case of severe renal biopsy complications in
      11-year-old with nephrotic syndrome.

PMID- 19580203
TI  - [Severe course of typical hemolytic-uremic syndrome in a 14-year-old boy].
AB  - The authors present a 14-year old boy with acute renal failure in the course of
      hemolytic-uremic syndrome (HUS), preceded by bloody diarrhea of unknown origin.
      The course of HUS was complicated with hypertensive crisis, pleural effusion.
      Pleural puncture was complicated with massive hemorrhage which required
      thoracotomy. Additional risk factor were subendocardial perfusion disorders found
      in MRI scan of the heart and peripheral peroneal nerve palsy (in neuro-motorical
      conduction examination--severe neuropathy). Renal replacement therapy was
      necessary for 11 days (hemodialyses--3 days, continuous hemodiafiltration--9
      days). Transfusions of: 3000 mL of packed erythrocyte mass, 2700 mL of fresh
      frozen plasma, 1000 mL of packed platelet mass were performed. Full parenteric
      nutrition was needed for 11 days. Full recovery of renal function, gradual
      improvement of heart muscle function, regression of lung abnormalities have been
      obtained.

PMID- 19580202
TI  - [Neurological symptoms in patient with focal segmental glomerulosclerosis treated
      with cyclosporin A--case report].
AB  - Cyclosporin A using in treatment glomerulonephritis can cause neurological side
      effects. CASE REPORT: Nephrotic syndrome (NS) with microscopic hematuria was
      recognized in a boy in the age of 9.7 years. In kidney biopsy focal and segmental
      glomerulosclerosis was found. Remission was obtained on oral prednisone (60 mg/24
      hrs). Second relapse of NS was treated with methylprednisolone pulse (VI pulses-
      600 mg/pulse) with a good effect. Third relapse of NS (secondary
      steroidoresistency) was treated with oral cyclophosphamide in a total dose 140
      mg/kg/therapy--the treatment was complicated by a massive oral cavity mycosis and
      sinusitis. 3 weeks after starting cyclosporine A (CsA) proteinuria subsided.
      During CsA treatment severe headaches and pains in orbits with nausea appeared.
      In neurological examinations no abnormalities were found, in ophthalmological
      examination--slight opacification of the lens was found. EEG revealed lesions
      localised in a posterior cerebral parts, and CT of the head showed slight
      dilatation of ventricles. In MRI foci of signal intensification were found in
      subcortical white substance. CsA was stopped after 4 months of the treatment and
      prednisone was stopped a month later. Control MRI after 6 months revealed
      maintenance of the foci in white substance. The patient is under nephrological
      care, has no proteinuria and no neurological symptoms. CONCLUSION: In patients
      treated with CsA appearance of headaches may suggest medication neurotoxicity.

PMID- 19580205
TI  - [Continuing education: how to reconcile needs and wants].

PMID- 19580204
TI  - [Cinacalcet in the treatment of secondary hyperparathyreoidism in a child with
      chronic kidney disease--case report].
AB  - The medical history and treatment of 2.5 years old girl with chronic kidney
      disease and heavy hyperparathyreoidism was presented in this case report. This
      girl was treated by peritoneal dialysis (APD) due to chronic kidney disease and
      congenital nephrotic syndrome. The secondary paraidothyreoidism was a reason of
      the epiphysial of the upper end of the femur, which appeared despite of the
      treatment by the Vitamin D3 (Calciphediol and Alphacalcidol) and phosphate
      binding drugs like Calcium Carbonate and Sevelamer. The primary laboratory tests
      were: Ca 9.32 mg/dl, Ca jon. 1.21 mmol/l, PO4 7.29 mg/dl, BE +4.9 mmol/l, ALP
      1425 U/l, PTH 3774 pg/ml, Albumins 3.23 g/l, Hgb 8.2 g/l. The treatment of
      cinacalcet (Mimpara, 30 mg, Amgen) in dose of 15 mg was started because of lack
      of the standard therapy results. The laboratory tests were controlled after 2
      weeks and then every week to 5th and every 2 weeks to the end. This therapy was
      finished after 30 weeks and only the standard therapy of hyperphosphatemia was
      continued. The laboratory tests 3 month after stopped the treatment were: Ca 10.5
      mg/dl, Ca jon. 1.36 mmol/l, PO4 4.0 mg/dl, BE +4.9 mmol/l, ALP 312 U/l, PTH 134
      pg/ml, Albumins 3.23 g/l, Hgb 9.9 g/l. There were any adverse events observed
      during the treatment. CONCLUSION: It seems, the cinacalcet may be an alternate
      treatment to paraidectomy in children with chronic kidney disease and heavy
      secondary hyperparathyreoidism.

PMID- 19580206
TI  - [The role of EGFR in non-small cell lung carcinoma].
AB  - EGFR receptor is expressed on most of the non small cell lung carcinoma (NSCLC)
      cells. Its relative importance in oncogenesis and tumour progression seems to
      greatly vary among NSCLC. Two molecules targeting differently EGFR are currently
      used for the treatment of metastatic NSCLC. cetuximab, a monoclonal antibody
      directed against the extracellular domain of the receptor, leads to a moderate
      survival benefit when associated with standard first-line chemotherapy.
      Erlotinib, a small EGFR tyrosine-kinase inhibitor molecule is used in 2nd or 3rd
      treatment line. Predictive factors for efficiency of these new treatments are
      subjects of intense research, in order to allow a better selection of the
      patients who could benefit from such a strategy.

PMID- 19580207
TI  - [Management of lymphoma and pregnancy].
AB  - With an incidence of 1/6000 pregnancies, per-partum lymphoma is a rare but not an
      exceptional event, which gynaecologists and family physicians can be confronted
      in the course of their career The diagnosis, without a peripheral adenopathy, can
      be challenging because symptoms, such as fatigue or dyspnoea, can easily be
      attributed to the pregnancy. Although the therapeutic management is complex,
      because it involves the mother and her embryos, it can be optimal in the majority
      of cases. The multidisciplinary management, with modern diagnostic and
      therapeutic approaches, greatly improved the prognosis of these young women.
      Today, it generally allows the safekeeping of the baby with an outcome for the
      mother identical to the one observed in the population at large.

PMID- 19580208
TI  - [Lymphoma and pruritus: search for parasites].
AB  - Strongyloides stercoralis is a parasite that can be acquired not only in tropical
      and subtropical areas, but also in some European countries. This helminthiasis is
      often a- or paucisymptomatic, and may persist in a latent state for several
      decades. In case of immunosuppression, a reactivation of the disease can occur,
      that may result in severe -- sometimes fatal -- complications, due to a syndrome
      of hyperinfestation. We present two cases of reactivation in patients suffering
      from lymphoma under chemotherapy. Screening of this parasite should be proposed
      for patients that have stayed in an endemic area before any corticotherapy or
      other immunosuppressive treatment, and in the presence of a disease reducing the
      immunity.

PMID- 19580209
TI  - [Colorectal cancer in elderly patients].
AB  - Colorectal cancer (CRC) is predominantly a disease of the elderly. The increase
      of life expectancy will no doubt lead to an increase of these cancers. Few
      studies have been specially designed for older patients treated for CRC. In
      general, publications consisted of small phase II studies or retrospective
      analyses of the subpopulation of elderly patients (from large phase III) --
      patients over the age of 65 as compared with younger patients. Therefore we now
      need to offer specific treatment combining oncologist and geriatric physicians to
      better codify and adapt treatments to the physiological age of the patient. This
      is a review of the different stages of care for elderly patients with colorectal
      cancer in the light of recent publications.

PMID- 19580210
TI  - [Bone metastases pain in the elderly].
AB  - Every year in Europe and in USA, more than 60% of new cases of cancer are
      diagnosed at the patient's of more than 65 years with a mortality of more than
      70%. Pain, is a major symptom which often accompanies cancer. It is always
      painful and intolerable, notably when pain is linked to bone metastases to
      elderly patients often poly pathological. In 1/3 of cases pain is present at the
      time of diagnosis of cancer and in 2/3 of cases at the advanced diseases. The
      bone metastases occupy the third place after the pulmonary and liver metastases.
      They are in order of frequency linked in breast cancer, the kidney and the
      prostate cancer. Bone metastases are at the origin of the loss of the elderly
      autonomy, with for consequence an impairment of quality of life. Validated tools
      are at now available to assess this pain. The different treatments offered in
      bone metastases pain are: the chemotherapy, the surgery, radiotherapy,
      bisphosphonates and analgesic treatment.

PMID- 19580211
TI  - [Acute coronary syndrome: guidelines and geriatrics specificity].
AB  - Acute coronary syndrome (ACS) includes unstable angina pectoris, myocardial
      infarction without ST elevation and myocardial infarction with ST elevation. ACS
      is more frequent in the elderly than in the general population and is associated
      with very high morbidity and mortality. As older individuals are often excluded
      from clinical trials, the geriatrician needs to take care of these subjects
      without specific guidelines. Although older subjects (or very old subjects)
      represent a group at high risk of complications, they would benefit most of an
      aggressive coronary revascularisation procedure. Given the current state of
      knowledge, biological age itself should not be the only limiting criteria when
      considering an invasive coronary procedure, but the existing quality of life and
      physical conditions of the individual should also be taken into account in the
      global management strategy.

PMID- 19580212
TI  - [Take nothing for granted...the risks of teleconsultation].

PMID- 19580213
TI  - [There won't be enough vaccines for the entire world].

PMID- 19580214
TI  - [Shedding new light on the placental barrier].

PMID- 19580215
TI  - [Physicians for and against masturbation].

PMID- 19580216
TI  - [The changes in physician revenue].

PMID- 19580217
TI  - [The need for limits].

PMID- 19580218
TI  - The 2009 Health Confidence Survey: public opinion on health reform varies; strong
      support for insurance market reform and public plan option, mixed response to tax
      cap.
AB  - PUBLIC SUPPORT FOR HEALTH REFORM: Findings from the 2009 Health Confidence Survey
      -the 12th annual HCS--indicate that Americans have already formed strong opinions
      regarding various aspects of health reform, even before details have been
      released regarding various key factors. These issues include health insurance
      market reform, the availability of a public plan option, mandates on employers
      and individuals, subsidized coverage for the low-income population, changes to
      the tax treatment of job-based health benefits, and regulatory oversight of
      health care. These opinions may change as details surface, especially as they
      concern financing options. In the absence of such details, the 2009 HCS finds
      generally strong support for the concepts of health reform options that are
      currently on the table. U.S. HEALTH SYSTEM GETS POOR MARKS, BUT SO DOES A MAJOR
      OVERHAUL: A majority rate the nation's health care system as fair (30 percent) or
      poor (29 percent). Only a small minority rate it excellent (6 percent) or very
      good (10 percent). While 14 percent of Americans think the health care system
      needs a major overhaul, 51 percent agree with the statement "there are some good
      things about our health care system, but major changes are needed." NATIONAL
      HEALTH PLAN ELEMENTS RATED HIGHLY: Between 68 percent and 88 percent of Americans
      either strongly or somewhat support health reform ideas such as national health
      plans, a public plan option, guaranteed issue, expansion of Medicare and
      Medicaid, and employer and individual mandates. MIXED REACTION TO HEALTH BENEFITS
      TAX CAP: Reaction to capping the current tax exclusion of employment-based health
      benefits is mixed. Nearly one-half of Americans (47 percent) would switch to a
      lower-cost plan if the tax exclusion were capped, 38 percent would stay on their
      current plan and pay the additional taxes, and 9 percent don't know. CONTINUED
      FAITH IN EMPLOYMENT-BASED BENEFITS, BUT DOUBTS ON AFFORDABILITY: Individuals with
      employment-based health benefits are confident that employers will continue to
      offer such benefits. They are much less confident that they would be able to
      afford coverage on their own, even if employers gave them the money they
      currently spend on health benefits. However, were employers to stop offering
      coverage, respondents report that they are likely to purchase it on their own.
      RISING HEALTH COSTS HURTING FAMILY FINANCES: Those experiencing health cost
      increases tend to say these increases have negatively affected their household
      finances. In particular, they indicate that increased health care costs have
      resulted in a decrease in contributions to a retirement plan (32 percent) and
      other savings (53 percent) and in difficulty paying for basic necessities (29
      percent) and other bills (37 percent). COSTS ALSO AFFECTING HEALTH CARE USE: Many
      consumers report they are changing the way they use the health care system in
      response to rising health care costs. Roughly 80 percent of those with higher out
      of-pocket expenses say these increased costs have led them to try to take better
      care of themselves and choose generic drugs more often. One-quarter also say they
      did not fill or skipped does of their prescribed medications in response to
      increased costs.

PMID- 19580219
TI  - [Mortality caused by injury, poisoning and other consequences of external causes
      in the Split-Dalmatia county population 2001-2005].
AB  - AIM: To present mortality caused by injury, poisoning and other consequences of
      external causes (S00-T98, ICD-10) in the Split-Dalmatia County population during
      the 2001-2005 period. METHODS: The methods of descriptive epidemiology were used.
      We included all County population with the diagnosis of fatal injuries (S00-T98,
      ICD-10) recorded during the study period. Mortality data were collected from the
      Central Bureau of Statistics. The distribution of mortality indicators according
      to the cause of death, age and sex is presented as absolute numbers, percentage
      and specific rates per 100,000 population. RESULTS: The group of injury,
      poisoning and other consequences of external causes (S00-T98, ICD-10) was the
      third or fourth leading cause of death in the County population, both males and
      females. During the study period, the specific injury mortality rates showed no
      significant oscillations. In this group, male subjects and those aged 75 or older
      were found to predominate. Concerning external causes of mortality, we determined
      the circumstances in which fatal injuries were inflicted. Falls were the leading
      cause of injury and death in females aged 75 or older. Traffic accidents
      predominantly involved younger and older males, while deliberate self-harm was
      most common in middle-aged and old aged subjects, male in particular. CONCLUSION:
      The role of public health is to point to the prevention of injuries because of
      their growing tendency in the population.

PMID- 19580220
TI  - [Health locus of control assessment in diabetes mellitus type 2 patients].
AB  - Health locus of control (LOC) refers to the person beliefs who or what has
      control over his/her health. A person's LOC orientation is one of several factors
      that determine which health-related behaviors a person will perform. AIM: To
      explore LOC of diabetes mellitus type 2 (DMT2) patients, also in relation to
      patient' socio-demographic characteristics (sex, education, working status, and
      family status), context (place of birth, experience with chronic diseases in
      family, economic status), social support and quality of life. METHODS: This cross
      sectional study was carried out in 77 DMT2 patients in two family medicine
      practices. Patients filled out two questionnaires: on patient general data and
      ZLK-90-2 questionnaire. Statistic analysis was done using Statistica, version 7.1
      software, and values of P < 0.05 were considered statistically significant.
      RESULTS: The patient mean age was 63.4 years +/- 13.1 (M +/- SD), and mean
      duration of diabetes 10.3 +/- 8.2 years (M +/- SD). The belief ininternal LOC was
      most common in study patients, followed by the belief in health dependence on
      circumstances, influence of chance, destiny or God, and finally influence of
      powerful others. Highly educated patients had a statistically significantly less
      expressed internal LOC and belief in the influence of chance, destiny or God. The
      patients that underestimated their quality of life, showed a statistically
      significantly lower rate of belief in health dependence on circumstances.
      DISCUSSION: In spite of the small sample size and unfavorable patient
      distribution according to age, work status, disease duration and education,
      results of this and other studies on LOC, forcing LOC orientation regarding self
      treatment and self-control of DMT2 patients could be of high importance, with the
      assumption of good internal responsibility and belief in help of other important
      people. CONCLUSION: Understanding LOC of DMT2 patients is essential for
      developing more efficient educative and intervention medical programs for care of
      these patients, since it could help in making the right access to care for every
      single patient or group of patients that have the same LOC.

PMID- 19580221
TI  - [Referring process in family medicine--contribution assessment].
AB  - AIMS: The aim of the study was to follow and analyze patient referrals from
      general practice (GP) to diagnostic procedures and specialist consultations. Data
      on the kinds of diagnostic procedures, specialist consultations and requests for
      referrals were collected. Specific aim was to assess the contribution of
      referring for definitive diagnosis and to compare the frequency and contribution
      of first and repeat consultations. METHODS: This prospective study was conducted
      in the course of one month at six GP practices (three urban and one rural
      practice in inland area, and one urban and one rural practice in coastal area of
      Croatia). Patient sociodemographic data (age and sex), referral request (by
      patient, GP, GP and specialist in agreement, specialist only) and kind of visit
      (first, follow-up) were collected. The contribution of referrals was assessed by
      GPs using modified Likert's scale (1-markedly significant, 2-significant, 3
      undetermined, 4-small and 5-insignificant). On comparison of frequencies chi
      square test was used. Statistical analyses were done by use of licensed software
      (SAS Institute Inc, Cary, NC, USA). RESULTS: During one month, 1815 patients were
      referred, 979 for diagnostic procedures and 836 for specialist consultation (mean
      age 55.25 +/- 19.70; male 56.30 +/- 19.10, female 54.50 +/- 20.30). Most frequent
      diagnostic procedures requested were biochemical laboratory in primary health
      care setting (n = 331; 33.41%) and secondary care (n =1 18; 12.05%), basic
      radiology (n=106; 10.83%), ultrasonography (n=87; 8.80%) and microbiological
      laboratory (n = 68; 6.95%). The contribution of diagnostic procedures was mostly
      assessed as significant (54.84%). When GP and specialist indicated diagnostic
      procedure concordantly, its contribution was mostly assessed as significant
      (61.90%) and markedly significant (10.12%). Specialist consultations were used as
      follows: physical medicine in 131 (19%), surgeon in 90 (13%) and psychiatrist in
      69 (10%) patients from inland area, cardiologist in 53 (37%), psychiatrist in 17
      (12%) and oncologist in 12 (8%) patients from coastal area. Both in rural and
      urban practices in inland and coastal area surgeon consultations were assessed as
      markedly significant. Urban GPs assessed the contribution of first and follow-up
      check ups as undetermined or small more often than rural GPs (first check ups
      Xchi =21.66; P<0.0001; follow-up check ups chi2 = 196.38; P < 0.0001). Rural GPs
      assessed the contribution of first check ups more often as undetermined or small
      than significant (chi2 = 12.02; P = 0.0005), with the same tendency recorded for
      follow-up check ups (Xchi =32.01; P < 0.0001). CONCLUSION: GP should maintain the
      gatekeeping role to assure good quality of care and rationality in using
      available resources. Cooperation between GPs and specialists is essential to
      achieve good quality of care. GPs should restore role in indicating follow-up
      check ups.

PMID- 19580222
TI  - [Epilepsy in the Split-Dalmatia county--prevalence and therapeutic approaches].
AB  - The aim of the study was to determine the prevalence of epilepsy in the Split
      Dalmatia County. The study was carried out in a sample of 140,493 County
      inhabitants. There were 883 epilepsy patients in the study sample, showing a male
      predominance. The prevalence of epilepsy was 6.29/1,000 inhabitants, roughly
      corresponding to the results recorded in other populations. The highest
      prevalence was found in Vrlika, where patients with severe mental retardation are
      institutionalized. Other places showed a uniform distribution. The mean patient
      age was 41.02b +/- 3.4 years, with a mean of 1.33 drugs per patient. There was no
      statistically significant sex difference in the number of drugs used. The largest
      number of patients were on monotherapy, wherease only 0.45% of patients were
      taking no therapy at all. Study results are consistent to those reported in
      developed countries.

PMID- 19580224
TI  - [Automatic refractometer in the evaluation of eye refraction in children].
AB  - Recent publications state that automatic refractometer is more precise than
      retinoscopy. The purpose of this study was to determine if there is significant
      difference in refractive values obtained by retinoscopy and by automatic
      refractometer. We examined 39 children (78 eyes) aged between 4 and 6 years.
      Retinoscopy after atropine midriasis and automatic refractometer measurements
      were done in all patients. We compared the values obtained with retinoscopy and
      automatic refractometer and found statistically significant differences in the
      sphere (T-test: t = 17,929, p < 0.001) and cylinder diopters (T-test: t = 3.052,
      P = 0.005) but in the axes (T-test: t = 0.319, P = 0.751). Therefore, we believe
      that retinoscopy remains the only precise method to evaluate eye refraction.

PMID- 19580223
TI  - [Video capsule endoscopy--preliminary experience in university hospital setting].
AB  - INTRODUCTION: The use of video capsule endoscopy (VCE) started in late 2001 when
      it was approved by the Food and Drug Administration (FDA). Since then, we are
      able to visualize small bowel mucosa with a minimally invasive technique, very
      comfortable for patients, with very few complications and without the need of
      hospitalization. At Dubrava University Hospital, we have been using VCE since
      October 2006, and by February 2008 we examined 30 patients. AIM: The aim of the
      study was to present our preliminary results in the use of VCE during a period of
      one year and five months. We also report indications and contraindications for
      VCE, and patient preparation. METHODS: In this retrospective study we reviewed
      records on 30 patients that had undergone VCE at Dubrava University Hospital,
      Zagreb, Croatia, between October 2006 and February 2008. The indications for VCE
      were restricted to the investigation of obscure gastrointestinal bleeding (OGIB)
      (n = 10), iron deficiency anemia (n = 2), suspected Crohn's disease (n = 1),
      assessment of known small bowel Crohn's disease (n = 5), unexplained diarrhea (n
      = 6), chronic abdominal pain (n = 3), suspected ganglioneurinoma (n = 1) and
      suspected polyposis syndrome (n = 2). To be eligible for VCE, patients had to
      have previously undergone usual diagnostic methods of upper endoscopy,
      colonoscopy and small bowel follow-through, without discovering the cause of
      their symptoms. Before swallowing the capsule, patients were instructed not to
      eat anything the day before VCE and to drink 4 L of liquids, and additional 2 L
      magnesium sulfate. In all patients we used Olympus EndoCapsule Software (Tokyo,
      Japan). Results were interpreted by one specialist, gastroenterologist. RESULTS:
      Definitive diagnosis was made in 15 patients. Suspect findings were noted in 2
      patients, whereas no diagnosis could be established in 13 patients. According to
      our experience, VCE is a promising new method that has a high diagnostic yield in
      patients with OGIB and known Crohn's disease. Use of VCE enabled definitive
      diagnosis to be made in 6 of 10 patients with OGIB after all previously used
      diagnostic methods had failed to reveal any pathological finding. In the group of
      OGIB patients, angiodysplasia was the most common findings (4 of 10 patients). In
      the group of patients with Crohn's disease, progression of the disease to
      neotherminal ileum was recorded in 3 of 5 patients. Our experience also confirmed
      the VCE to be a very safe method; capsule retention was recorded in only one
      patient. DISCUSSION: Although VCE enabled us to visualize the small bowel mucosa
      and therefore helped us establish the diagnosis in cases where other diagnostic
      methods had failed, it still has some important limitations, the major one being
      the impossibility to take biopsies and to perform any therapeutic procedures.
      However, it has a high diagnostic yield in cases of OGIB and Crohn's disease, is
      very comfortable for patients, and has a low incidence of complications (capsule
      retention). When making definitive diagnosis, one should always consider
      patient's history and physical examination findings as well as other possible
      causes of small bowel mucosal impairment. CONCLUSION: VCE is a promising new
      technique that has a high diagnostic yield in patients with OGIB and Crohn's
      disease. However, more studies need to be done to establish definitive
      indications, cost-effectiveness and the best way of patient preparation for VCE.

PMID- 19580225
TI  - [The incidence of nonarteritic ischemic optic neuropathy in the Split-Dalmatia
      County].
AB  - The aim of this study was to determine the incidence of nonarteritic ischemic
      optic neuropathy (NAION) in the Split-Dalmatia County, Croatia, as part of the
      Mediterranean region of southern Europe, during a 7-year period (2001-2007). This
      retrospective study included 87 NAION patients (36 female, median age 68 years,
      and 51 male, median age 69.5 years) treated at University Department of
      Ophthalmology, Split University Hospital Center, from January 2001 till December
      2007. In each case the diagnosis was confirmed by review of patient records. The
      annual incidence of NAION was 2.9 per 100,000 (95% CI 1.1-4.8); 3.8 (95% Cl 0.76
      6.8) per 100,000 per year in male and 2.5 (95% CI 0.12-4.9) per 100,000 per year
      in female patients. There was no statistically significant sex difference in the
      annual incidence of NAION (chi2 = 1.17; P = 0.279). NAION involvement showed a
      statistically significant male predominance in the > 65 year age group, yielding
      a relative risk for men vs. women of 1.75. In conclusion, the incidence of NAION
      in the Split-Dalmatia County was found to be moderate.

PMID- 19580226
TI  - [Statin prescribing in the City of Zagreb (2001-2006) and their role in secondary
      prevention of cardiovascular events].
AB  - INTRODUCTION: Cardiovascular drugs account for 40% of total outpatient drug
      utilization in the City of Zagreb. Among them, utilization of the group of
      hypolipemics showed greatest rise from 2001 to 2006. AIM: The aim of the study
      was to investigate outpatient utilization of hypolipemics in the City of Zagreb
      during the 2001-2006 period and to assess the quality of prescribing these drugs
      in primary health care. METHODS: The number of defined daily doses (DDD) and DDD
      per 1000 Zagreb inhabitants per day (DDD/1000/day) were calculated on the basis
      of data on the number of packages of each individual hypolipemic (C10) for each
      study year. Data on the rate of hospitalization for the leading cardiovascular
      complications were collected as indirect indicators of the statin prescribing
      quality. RESULTS: The utilization of hypolipemics was 33.03 DDD/1000/day in 2001
      and 72.38 DDD/1000/day in 2006, yielding an almost twofold rise. Two drugs,
      simvastatin and atorvastatin, predominated in the utilization of statins with
      93%. From 2001 to 2006, the utilization of simvastatin showed a 30% increase and
      that of atorvastatin more than sevenfold increase. During the study period, the
      overall rate of hospitalization for cardiovascular disorders decreased by 18.5%.
      CONCLUSION: The decreasing tendency recorded in hospitalization for
      cardiovascular diseases points to the improved quality of secondary prevention,
      including statins. The high rate of hospitalization for hypertension reflects
      inadequate primary prevention of cardiovascular disorders.

PMID- 19580227
TI  - [A patient with 16 liter blood loss during radical prostatectomy].
AB  - Radical prostatectomy is the treatment of choice for localized prostate neoplasm.
      Bleeding is a common problem during this operation. Massive bleeding can occur in
      case of injury of one of the hypogastric vein branches during lymphadenectomy or
      transection of the dorsal vein plexus. We present a 67-year-old patient that lost
      16 liters of blood during the operation. In order to restitute the lost blood
      volume and prevent the low cardiac output and hypoxia, the patient was
      administered crystalloids, colloids, blood and blood derivatives. The patient
      received epinephrine, norepinephrine and dopamine to maintain mean arterial
      pressure above 55 mm Hg. After stopping surgical bleeding, stabilization of the
      coagulation system was achieved and further nonsurgical bleeding prevented by
      aprotinin and recombinant factor VIla. Timely volume restitution, not only with
      blood and blood components, was crucial to prevent the consequences of
      hemorrhagic shock. With pharmacological interventions, by aprotinin and
      recombinant factor VIIa in particular, we can act prophylactically and
      therapeutically to stop nonsurgical bleeding. Multimodal therapeutic procedures,
      promptly administered in massive bleeding, can improve the survival prognosis.

PMID- 19580228
TI  - [Stabs medici and physicians in Bjelovar in the 18th and 19th century].
AB  - During the 18th and 19th century, the first military physician (Stabs Medicus) in
      the town of Bjelovar and Bjelovar County arrived with the establishment of town
      authorities and settling of the Border regiment troops in the surrounding areas
      along the Croatian Military Border. Previously unknown data on the historical
      development of military and civilian physician service in Bjelovar are presented.

PMID- 19580229
TI  - [Importance of medical treatment in second echelon during war in Croatia, example
      -war surgical hospital in Garesnica].
AB  - At beginning of 1991, the increasing necessity of emergency surgical treatment of
      wounded persons in Croatia led to the formation of mobile surgical teams.
      However, this system was abandoned due to many problems and echelon health
      division was formed. One of the war surgical hospitals (second echelon) was the
      War Surgical Hospital Garesnica. In this study, materials of the Croatian War
      Veterans Ministry, Ministry of Defense, Garesnica War Surgical Hospital and
      Garesnica Defense Office archive were used. We analyzed the number and
      localization of wounds, and describe the organization, work and results of the
      War Surgical Hospital in Garesnica. During the work of the War Surgical Hospital
      in Garesnica, 909 surgical examinations were performed, 521 wounded were
      surgically treated (45% civilians and 55% soldiers), 331 wounded were operated
      on, 5 lethal outcomes were recorded, 68% of wounds were localized on the
      extremities, 19% on the thorax and abdomen, and 13% on the head end neck. In this
      article the organization and work of the War Surgical Hospital in Garesnica is
      described, which had a major role in providing emergency medical care to people
      wounded in west Slavonia.

PMID- 19580230
TI  - [Hearing damage as a consequence of firefighters' professional exposure to
      noise].
AB  - The aim of the study was to find out whether firefighters' professional exposure
      to the noise of sirens, motor water pumps and transportation by heavy vehicles
      causes biauricular hearing impairment. Furthermore, on the basis of the results
      the aim was to find out whether it is necessary to launch a hearing preservation
      program and additional health protection measures for this specific working
      population. The method of physical examination and audiometry was used. Thirty
      four professional firefighters from Opatija and 30 workers of Rijeka Promet
      employed at the town parking lots underwent audiometry on a Sibelmed AC 50 device
      and then analyzed. The results of biauricular audiometry showed significant
      differences in hearing damage between the firefighters and Rijeka Promet
      employees at higher frequencies where hearing damage begins, i.e. at 4 kHz and 8
      kHz (P < 0.05). The firefighters' maximal hearing loss of 30.58 +/- 24.66 dB for
      the right ear at 4 kHz and of 28.52 +/- 24.66 dB for the right ear at 8 kHz were
      higher than the hearing loss of the parking lot employees with maximal hearing
      loss of 17.00 +/- 13.10 dB at 4 kHz and of 16.33 +/- 13.89 dB at 8 kHz. The
      results of left ear audiometry were very close to those of right ear in both
      groups of subjects. The linear regression analysis yielded almost identical
      positive correlation between the time spent at the job and hearing damage, with
      correlation factor r = +.55 for the right and left ear at 4 kHz. The noise was
      measured at the Opatija Fire Station. Several measurements were performed: on the
      premises where firefighters are exposed to so-called communal noise, measurements
      at 2 m of the fire truck when sirens are sounded, noise measurements in driver's
      cab when sirens are sounded, and the noise made by motor water pump used in
      firefighting. Also, measurements were performed on the spot, i.e. at the working
      place of parking lot employees in the center of Rijeka where they stay most of
      the time, and on the street by the parking lot. It may be concluded that noise
      induced hearing damage in firefighters is a major problem in this working
      population, their physical and mental condition being very good, which is to be
      expected of the groups of operatives on whom the lives of "ordinary" people often
      depend. Hearing damage is the only weak point of firefighters, although fairly
      mild to moderate at higher frequencies, so medical experts in cooperation with
      their chiefs should persuade them to wear hearing protection, which could be
      discomforting in firefighting operations. Firemen are employed mainly at a young
      age when their hearing is normal. A parallel may be drawn with the military.
      Professional soldiers who are physically perfectly fit, at periodical medical
      examinations are often assessed as "limited service" due to hearing damage,
      although their hearing was good when they started the career. Hearing in the
      young population is generally good, in Primorje-Gorski Kotar County the average
      hearing level is 10 dB at all routine frequencies on audiometry, so hearing
      damage is not among illnesses that might cause difficulties to young recruits. To
      conclude, to preserve good hearing in both young and experienced firefighters,
      the Hearing Preservation Program should be more strictly implemented in the
      Primorje-Gorski Kotar County.

PMID- 19580231
TI  - Sixtieth anniversary of the University of the West Indies.

PMID- 19580232
TI  - Extending the art of medicine.

PMID- 19580233
TI  - The evolution of undergraduate medical training at the University of the West
      Indies, 1948-2008.

PMID- 19580234
TI  - The Faculties and School of Medical Sciences of The University of The West Indies
      at its diamond jubilee.

PMID- 19580236
TI  - Can research accelerate progress toward millennium development goal 5 (maternal
      health) in Jamaica?
AB  - The Ministry of Health and the University of the West Indies have collaborated
      over 25 years to develop the evidence base to improve maternal health. The
      experience is reviewed as a model to accelerate Jamaica's progress toward
      achieving the Millennium Development Goals (MDGs). The process included measuring
      the disease burden due to maternal morbidity and mortality; developing and field
      testing interventions to manage the leading problems, national scale-up,
      monitoring and evaluation. This began with developing clinical guidelines to
      manage the hypertensive disorders of pregnancy while establishing high risk
      (referral) antenatal clinics, expansion and upgrading of referral facilities, and
      audits to identify barriers to quality healthcare, including establishing
      maternal mortality surveillance. As we succeed, research funds have become
      scarce, limiting support to postgraduate students, a reliable, cost effective
      resource pool capable of undertaking the research needed to provide the evidence
      base to influence public policy more widely. A locally financed resource pool is
      needed to support fellowships for graduate students to accelerate their training
      and availability to contribute to national development. The model from Thailand
      is put forward for consideration. The operations research model for maternal
      health can be transferred to other MDG objectives. As Jamaica pursues its goal of
      developed nation status, and international grant financing shrinks, local civil
      society will need to fill the vacancy and invest in the most abundant natural
      resource, young people.

PMID- 19580235
TI  - Health human resource planning in Barbados and the eastern Caribbean states: a
      matter of sustainability.
AB  - Health and Human Resources (HHR) are very important issues to be considered in
      healthcare services. While various factors may be of greater significance in one
      area depending on resources, priorities and stage of economic development, a
      robust HHR plan is important in all cases. There are many factors such as
      demographic shifts, changing delivery models, consumer expectations, global
      shortages and financial restraints that must be considered in proper HHR
      planning. This manuscript summarizes some of the factors that should be
      considered and some of the short comings of current HHR planning approaches.
      Based on our review and experience, we developed a framework for HHR planning and
      apply the framework to Barbados to try to identify the existing challenges and
      issues and potential areas for staff and training investments.

PMID- 19580237
TI  - Integrating research into policy and programmes. Examples from the Jamaican
      experience.
AB  - Research into selected health problems across the life cycle are discussed with
      respect to the application and impact of the findings on policy, programme
      development and health outcomes. Special emphasis is placed on health research
      that focussed on the perinatal period, the young child and adolescent, the
      epidemics of chronic diseases and violence and the linkage between health and
      tourism. The lessons learnt over more than two decades of practice in the field
      of public health from conducting research aimed at developing an indigenous
      evidence base for policies and programmes in Jamaica are summarized.

PMID- 19580238
TI  - A comprehensive response to the HIV/AIDS epidemic in Jamaica: a review of the
      past 20 years.
AB  - Jamaica has a well-established, comprehensive National Human Immunodeficiency
      Virus (HIV) programme that has slowed the HIV epidemic and mitigated its impact.
      Adult HIV prevalence has been stable at approximately 1.5% since 1996. HIV rates
      are high among those most at risk such as sex-workers (9%) and men who have sex
      with men [MSM] (31.8%). Risk behaviour among adults with AIDS includes multiple
      sexual partners (80%), a history of a sexually transmitted infection [STI]
      (51.1%), commercial sex (23.9%) and crack/cocaine (8.0%). Approximately 20% of
      all reported AIDS cases, mainly women, give no history of any of the usual risk
      factors for HIV infection. The national programme is based in the Ministry of
      Health. Since 1988, Jamaica has had a national plan to guide its HIV response. A
      National AIDS Committee was established in 1988 to lead the multi-sectoral
      response. Prevention approaches have included information, education and
      communication campaigns, condom promotion, sexually transmitted infections (STI)
      control, targeted interventions, cultural approaches, outreach and peer
      education, workplace programmes and HIV counselling and testing. Concerted
      efforts have been made to reduce HIV stigma and discrimination. Antiretroviral
      therapy (ARV) was introduced for prevention of mother-to-child transmission in
      2001 and a public access treatment programme introduced in 2004. A national
      HIV/AIDS Policy was adopted unanimously in parliament in 2005. The National
      Strategic plan 2007-2012 commits Jamaica to achieving universal access to
      HIVprevention, treatment and care. Awareness of HIV and how to prevent it is near
      universal though belief in myths remains strong. The condom market has increased
      from approximately 2.5 million in 1985 to 12 million in 2006 while condom use has
      grown significantly with nearly 75% of men and 65% of women reporting condom use
      at last sex with a non-regular partner The proportion of women 15-24 years
      reporting ever having a HIV test increased from 29.8% in 2004 to 48.9% in 2008.
      HIV transmission from mother-to-child has declined from 25% prior to 2000 to less
      than 8% in 2007. As of September 2008, 4450 persons or an estimated 68.5% of
      persons with advanced HIV and AIDS have been placed on ARV treatment resulting in
      a significant decline in mortality and morbidity due to HIV

PMID- 19580239
TI  - Ageing: the response yesterday, today and tomorrow.
AB  - This is an overview of the phenomenon of population ageing and ageing trends in
      Jamaica. It documents landmark policy achievements and responses to population
      ageing and analyses related social, economic and health implications, as well as,
      the challenges and opportunities of ageing. The interdigitations of ageing issues
      and public health is manifest from the early historical milestones in ageing
      research to the establishment of the Mona Ageing and Wellness Centre to the
      continuing collaborative work with international agencies such as the World
      Health Organization (WHO). The contribution of the University of the West Indies
      (UWI) through the Department of Community Health and Psychiatry to ageing
      research and policy is documented.

PMID- 19580240
TI  - The elderly in Trinidad: health, social and economic status and issues of
      loneliness.
AB  - OBJECTIVES: To determine the general health and social status of elderly persons
      surveyed in Trinidad and to explore issues of loneliness. METHOD: An island-wide
      survey of persons aged 65 years and older was conducted in early 2002 in Trinidad
      Eight hundred and forty-five (845) elderly persons were chosen using systematic
      random sampling. The main survey instrument for data collection was a
      questionnaire that included structured as well as open-ended questions. The
      subjects were chosen in a house-to-house survey conducted in all eight counties
      in Trinidad. Elderly people who were unable to comprehend the questions were
      excluded from the survey. RESULTS: Those selected ranged in age from 65-102 years
      and represented all the ethnic groups in Trinidad. These elderly persons lived in
      a wide range of housing situations. The majority lived in the homes of family
      members (57%) and 16% lived on their own. A large proportion (80%) had at least
      one chronic medical problem, although 44% reported their health as "fairly good"
      or "good". More than a half of the males (53%) and 67% of the females were taking
      at least one prescribed medicine. The main sources of income were old age pension
      (85%) and National Insurance (15%). Thirty-three per cent reported feelings of
      loneliness. This figure includes 28% of those who did not live alone. CONCLUSION:
      The data revealed that across all ethnic groups more than one-third of the sample
      reported themselves to be in fair to good health. Many of these elders were
      lonely because their relatives were quite occupied with their own affairs.

PMID- 19580241
TI  - Medical sociology: modelling well-being for elderly people in Jamaica.
AB  - OBJECTIVE: Advances in nutrition, sanitation, water supply, technology and drugs
      have managed to add years to life. However, with the continuing increase in the
      non-communicable diseases, the World Health Organization (WHO) has said that
      disabilities have eroded nine years from the healthy quality of life of
      Jamaicans. The current study aims to provide factors that will explain how to
      attain 'good' health. METHOD: The research design for this study is an
      explanatory one. This research utilizes cross-sectional data taken from the
      Jamaica Survey of Living Conditions (JSLC) 2002 in order to identify and explain
      some of the determinants of well-being among the Jamaican elderly. Information
      collected used self-administered questionnaire. Multivariate regression was used
      to establish the well-being model. The surveyedpopulation was 3009 respondents
      ages 60 years and older, with 52.7% females (n=1423) and 47.3% males (n=1423).
      The average age of the surveyed population was 71 years 10 months +/- 8 years six
      months. RESULT: Of the 14 predisposed variables that were used to test the
      general hypothesis, 11 were found to be statistically significant. From the
      selected variables of this study, the six most important factors that impact on
      the well-being of the Jamaican elderly in descending order are as follows: social
      support (beta = 0.486), average occupancy per room (beta = -0.428), area of
      residence--living in Kingston Metropolitan Area (KMA) with reference to rural
      areas (beta = 0.179) or dwelling in other towns with reference to rural area
      (beta = 0.157), education (beta = 0.155) followed by the physical environment
      (beta = -0.138) and age of respondents (beta = -0.129). CONCLUSION: The
      predisposed variables used in this study explain 45.9% of the variance in quality
      of life. The variable that has the most influential impact on well-being is
      social support. The general wellbeing of the Jamaican elderly is low (mean of
      3.9/14 +/- 2.3). The model provides a basis upon which we can address patient
      care and 'good' health.

PMID- 19580242
TI  - Diseases and medical disabilities of enslaved Barbadians from the seventeenth
      century to around 1838. Part I.
AB  - The disease environment, health problems and causes of mortality of enslaved
      Barbadians are described. Data are derived mainly from documentary sources; also
      included are bio-archaeological data from analyses of skeletons recovered from
      Newton Plantation cemetery. Major topics include infectious diseases transmitted
      from person to person, as well as those contracted through water soil, and other
      environmental contaminations, and diseases transmitted by insects, parasites, and
      other animals; nutritional diseases, including protein energy malnutrition,
      vitamin deficiencies, anaemia, and geophagy or "dirt eating"; dental pathologies;
      and lead poisoning, alcoholism, traumas, and other disorders, including
      psychogenic death or illness caused by beliefs in witchcraft or sorcery.

PMID- 19580243
TI  - The anatomy and physiology of the medical class of 1982a.
AB  - BACKGROUND: Studies of medical student outcome have been used to assist in
      medical manpower planning. There have been no published studies on medical
      graduates of The University of the West Indies (UWI), This study Investigates the
      demographic characteristics, professional and social outcomes of the Class of
      1982a, twenty-five years after qualification. METHOD: Data on demographic
      characteristics at entry and academic performance during medical school were
      obtained from UWI administrative records. Data on specialty training, migration
      and current social status were obtained by interview. Statistical analysis was
      conducted using simple frequencies, chi-square and t-tests. RESULTS: There was an
      intake of 110 students with 108 completing the course. The mean age at entry was
      21.8 +/- 3.0 years; 74.0% were male, Some 80.6% of students were from Jamaica,
      Trinidad and Tobago, and Barbados. Only 15.7% were admitted directly from high
      school. A quarter of students were scholarship awardees, with the majority being
      from Eastern Caribbean countries (p < 0.001). Female students outperformed male
      students (p < 0.05), Just over 70% of graduates pursued postgraduate training,
      the majority in North America. Approximately two-thirds of graduates were
      practicing in the Caribbean region. Almost all graduates (95.0%) trained in the
      Caribbean were practicing in the region but less than a thitrd of those trained
      elsewhere were (p < 0.001). CONCLUSION: This study has provided important
      information on choice of specialty training, migration and the associated factors
      twenty-five years ago. The information provided can therefore be used as a base
      for examining the trends in medical education over time and the factors
      influencing these trends, allowing for better planning of the manpower needs of
      the region.

PMID- 19580244
TI  - A neuropathic syndrome of uncertain origin: review of 100 cases.

PMID- 19580245
TI  - Doctor of medicine training--reflections on the UWI (Mona) experience.
AB  - Postgraduate Doctor of Medicine (DM) training at the University of the West
      Indies (UWI) has grown in response to the need to meet the regional requirements
      for high quality, competent clinical specialists. The progress of these
      programmes are examined from historical and health manpower development
      perspectives. More than 600 persons have been trained through the DM programmes
      at UWI, Mona and 89% of them continue to provide critical services in the region.
      Such statistics underscore the success of the programme in meeting the Caribbean
      Corporation in Health (CCH), UWI and Faculty of Medical Sciences (FMS)
      objectives. The relevance of the programme to the Caribbean's needs is manifestly
      clear Curriculum changes including a mandatory research component for all DM
      degrees reflect the evolution of training programmes as they adjust to current
      expectations of modern clinical practice and new emphases on evidence-based
      medicine and policies. Nevertheless, challenges exist including the deterioration
      of the physical plant for training, availability of training posts and funding of
      research. Monitoring, evaluation and quality assurance of existing programmes are
      to be continued.

PMID- 19580246
TI  - Comprehensive longitudinal studies of child health, development and behaviour in
      Jamaica: findings and policy impact.
AB  - BACKGROUND: Birth cohort and other longitudinal studies of children's health,
      development and behaviour have provided important information on child and adult
      outcomes. This has allowed evidence based policy and programme development
      targeted at issues specific to countries. Few studies have been conducted in
      developing countries. This paper reports on the findings and policy implications
      of two comprehensive longitudinal studies in Jamaica. METHOD: The findings of the
      Jamaican Birth Cohort Studies, conducted between 1986 and 2003, and the Profiles
      Project, a longitudinal study commencing in 1999 when children were six years,
      were reviewed. Recommendations from the studies and their impact on policy and
      programme development for Jamaican children were identified. RESULTS: Policy and
      programme impact were identified in areas of child poverty intervention,
      parenting, social activities, violence and aggression, health and nutrition,
      screening and early intervention, setting of standards for early childhood
      institutions, gender early childhood indicators and education and training.
      Policy and programme impact were national, regional and international.
      CONCLUSION: Comprehensive longitudinal studies of children in developing
      countries, though costly, provide wide-ranging and important information for
      policy and programme development.

PMID- 19580247
TI  - Highly regio- and enantioselective organocatalytic conjugate addition of alkyl
      methyl ketones to a beta-silylmethylene malonate.
AB  - (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid (3:1) combination
      catalyzed the direct addition of alkyl methyl ketones to beta
      dimethyl(phenyl)silylmethylene malonate at the methyl terminal with high yield
      and excellent regio- and enantioselectivity. The silyl group played crucial roles
      in regioselection and substrate reactivity.

PMID- 19580248
TI  - Sorbate-nitrite interactions: acetonitrile oxide as an alkylating agent.
AB  - Because chemical species with DNA-damaging and mutagenic activity are formed in
      sorbate-nitrite mixtures and because sorbic acid sometimes coexists with nitrite
      occurring naturally or incorporated as a food additive, the study of sorbate
      nitrite interactions is important. Here, the alkylating potential of the products
      resulting from such interactions was investigated. Drawn were the following
      conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the
      alkylating capacity of sorbate-nitrite mixtures; (ii) ACNO alkylates 4-(p
      nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic
      characteristics similar to those of DNA bases, forming an adduct (AD; epsilon =
      1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction
      complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]
      k(hyd)(AD)[AD], k(alk)(ACNO) being the NBP alkylation rate constant for ACNO and
      k(hyd)(AD) the rate constant for the adduct hydrolysis reaction; (iv) the small
      fraction of ACNO forming the adduct with NBP, as well as the small magnitude of
      the quotient (k(alk) (ACNO)/k(hyd)(ACNO)) as compared with those reported for
      other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas,
      reveals the ACNO effective alkylating capacity to be less significant; (v) the
      low value of the NBP-ACNO adduct life (defined as the total amount of adduct
      present along the progression of the NBP alkylation per unit of alkylating agent
      concentration) points to the high instability of this adduct; and (vi) the
      obtained results are in accordance with the low carcinogenicity of ACNO.

PMID- 19580250
TI  - Freezing-induced phase separation and spatial microheterogeneity in protein
      solutions.
AB  - Amid decades of research, the basic mechanisms of lyo-/cryostabilization of
      proteins and more complex organisms have not yet been fully established. One
      major bottleneck is the inability to probe into and control the molecular level
      interactions. The molecular interactions are responsible for the significant
      differences in the outcome of the preservation processes. (1) In this
      communication, we have utilized confocal Raman microspectroscopy to quantify the
      freezing-induced microheterogeneity and phase separation (solid and liquid) in a
      frozen solution composed of a model protein (lysozyme) and a lyo-/cryoprotectant
      (trehalose), which experienced different degrees of supercooling. Detailed
      quantitative spectral analysis was performed across the ice, the freeze
      concentrated liquid (FCL) phases, and the interface region between them. It was
      established that the characteristics of the microstructures observed after
      freezing depended not only on the concentration of trehalose in the solution but
      also on the degree of supercooling. It was shown that, when samples were frozen
      after high supercooling, small amounts of lysozyme and trehalose were occluded in
      the ice phase. Lysozyme preserved its native-like secondary structure in the FCL
      region but was denatured in the ice phase. Also, it was observed that induction
      of freezing after a high degree of supercooling of high trehalose concentrations
      resulted in aggregation of the sugar and the protein.

PMID- 19580251
TI  - Chemical reactivity descriptors for ambiphilic reagents: dual descriptor, local
      hypersoftness, and electrostatic potential.
AB  - The second-order response of the electron density with respect to changes in
      electron number, known as the dual descriptor, has been established as a key
      reactivity indicator for reactions like pericyclic reactions, where reagents
      accept and donate electrons concurrently. Here we establish that the dual
      descriptor is also the key reactivity indicator for ambiphilic reagents: reagents
      that can act either as electrophiles or as nucleophiles, depending on the
      reaction partner. Specifically, we study dual atoms (which are proposed to act,
      simultaneously, as an electron acceptor and an electron donor), dual molecules
      (which react with both electrophiles and nucleophiles, generally at different
      sites), and dual ion-molecule complexes (which react with both cations and
      anions). On the basis of our analysis, the dual atom (an Al(I) that has been
      purported to be dual in the literature) is actually pseudodual in the sense that
      it does not truly accept electrons from a nucleophiles; rather, it serves as a
      conduit through which an electrophile can donate electrons to the attached
      aromatic ring. For understanding dual ion-molecule complexes, it helps to
      understand that the dual descriptor makes a key contribution to the long-range
      portion of the quadratic hyperpolarization. In all cases, a complete description
      of the reactivity of the ambiphilic reagent requires considering both an orbital
      based descriptor of electron transfer (the dual descriptor or the local
      hypersoftness) and the electrostatic potential. The local hypersoftness strongly
      resembles the dual descriptor.

PMID- 19580249
TI  - Effect of cross-link structure on DNA interstrand cross-link repair synthesis.
AB  - DNA interstrand cross-links (ICLs) are products of chemotherapeutic agents and
      cellular metabolic processes that block both replication and transcription. If
      left unrepaired, ICLs are extremely toxic to cells, and ICL repair mechanisms
      contribute to the survival of certain chemotherapeutic resistance tumors. A
      critical step in ICL repair involves unhooking the cross-link. In the absence of
      a homologous donor sequence, the resulting gap can be filled in by a repair
      synthesis step involving bypass of the cross-link remnant. Here, we examine the
      effect of cross-link structure on the ability of unhooked DNA substrates to
      undergo repair synthesis in mammalian whole cell extracts. Using 32P
      incorporation assays, we found that repair synthesis occurs efficiently past the
      site of damage when a DNA substrate containing a single N4C-ethyl-N4C cross-link
      is incubated in HeLa or Chinese hamster ovary cell extracts. This lesion, which
      can base pair with deoxyguanosine, is readily bypassed by both Escherichia coli
      DNA polymerase I and T7 DNA polymerase in a primer extension assay. In contrast,
      bypass was not observed in the primer extension assay or in mammalian cell
      extracts when DNA substrates containing a N3T-ethyl-N3T or N1I-ethyl-N3T cross
      link, whose linkers obstruct the hydrogen bond face of the bases, were used. A
      modified phosphorothioate sequencing method was used to analyze the ICL repair
      patches created in the mammalian cell extracts. In the case of the N4C-ethyl-N4C
      substrate, the repair patch spanned the site of the cross-link, and the lesion
      was bypassed in an error-free manner. However, although the N3T-ethyl-N3T and N1I
      ethyl-N3T substrates were unhooked in the extracts, bypass was not detected.
      These and our previous results suggest that although the chemical structure of an
      ICL may not affect initial cross-link unhooking, it can play a significant role
      in subsequent processing of the cross-link. Understanding how the physical and
      chemical differences of ICLs affect repair may provide a better understanding of
      the cytotoxic and mutagenic potential of specific ICLs.

PMID- 19580252
TI  - Mechanism of ligand-induced folding of a natively unfolded helixless variant of
      rabbit I-BABP.
AB  - Substitution of the helix-turn-helix capping motif (residues 9-35) of rabbit I
      BABP with a flexible Gly-Gly-Ser-Gly linker results in the loss of stabilizing
      hydrophobic contacts and renders the beta-clamshell structure of this steroidal
      bile acid transport protein unfolded. However, in the presence of a bile acid
      ligand, we observe strong coupling between binding and folding, resulting in an
      enthalpy-driven high-affinity interaction (K(A) approximately 4 x 10(5) M(-1))
      that "rescues" the native state. We investigate the mechanism of induced folding
      using fluorescence stopped-flow kinetic measurements to distinguish between
      conformational selection and induced-fit models. We observe both ligand-dependent
      and -independent kinetic phases which, together with their relative amplitudes,
      we attribute to an induced-fit "fly casting" type of model in which transient
      encounter complexes between the ligand and the extended polypeptide chain may act
      as nucleation sites for folding. An initial fast ligand-dependent kinetic process
      appears to be consistent with formation of a hydrophobically collapsed
      intermediate state which slowly rearranges to a nativelike beta-clamshell
      structure. We show that the intermediate forms at a rate 1000 times slower than
      the rate of ligand association with wild-type I-BABP, reflecting the large
      configurational entropic barrier to the coupled binding and folding steps of
      Deltaalpha-I-BABP. We have provided mechanistic insights into how natively
      disordered states, now commonly identified in biology, may fold on binding a
      target substrate or ligand.

PMID- 19580254
TI  - Analysis of bacteria on steel surfaces using reflectance micro-Fourier transform
      infrared spectroscopy.
AB  - Reflectance micro-Fourier transform infrared (FT-IR) analysis has been applied to
      characterize biofilm formation of Aquabacterium commune, a common microorganism
      present on drinking water distribution systems, onto the increasingly popular
      pipe material stainless steel EN1.4307. The applicability of the reflectance
      micro-FT-IR technique for analyzing the bacterial functional groups is discussed,
      and the results are compared to spectra obtained using more conventional FT-IR
      techniques: transmission micro-FT-IR, attenuated transmitted reflectance (ATR),
      and KBr pellets. The differences between the infrared spectra of wet and dried
      bacteria, as well as free versus attached bacteria, are also discussed. The
      spectra obtained using reflectance micro-FT-IR spectroscopy were comparable to
      those obtained using other FT-IR techniques. The absence of sample preparation,
      the potential to analyze intact samples, and the ability to characterize opaque
      and thick samples without the need to transfer the bacterial samples to an
      infrared transparent medium or produce a pure culture were the main advantages of
      reflectance micro-FT-IR spectroscopy.

PMID- 19580255
TI  - Single-ion entropies, S(ion)(o), of solids--a route to standard entropy
      estimation.
AB  - Single-ion standard entropies, S(ion)(o), are additive values for estimation of
      the room-temperature (298 K) entropies of ionic solids. They may be used for
      inferring the entropies of ionic solids for which values are unavailable and for
      checking reported values, thus complementing the independent method of estimation
      from molar volumes (termed volume-based thermodynamics). Current single-anion
      entropies depend on the charge of the countercation, and so are difficult to
      apply to complex materials, such as minerals. The analysis of reported data here
      presented provides a self-consistent set of entropies for cations and charge
      independent values for anions. Although the S(ion)(o) values presented encompass
      only a limited set of ions, the retrieval of values for ions not listed is
      straightforward and is described. An unexpected and significant observation is
      that cation entropies are related to the molar volumes of the corresponding
      (neutral) condensed-phase metals.

PMID- 19580253
TI  - Steady-state and stopped-flow kinetic studies of three Escherichia coli NfsB
      mutants with enhanced activity for the prodrug CB1954.
AB  - The enzyme nitroreductase, NfsB, from Escherichia coli has entered clinical
      trials for cancer gene therapy with the prodrug CB1954 [5-(aziridin-1-yl)-2,4
      dinitrobenzamide]. However, CB1954 is a poor substrate for the enzyme. Previously
      we made several NfsB mutants that show better activity with CB1954 in a cell
      killing assay in E. coli. Here we compare the kinetic parameters of wild-type
      NfsB with CB1954 to those of the most active single, double, and triple mutants
      isolated to date. For wild-type NfsB the global kinetic parameters for both
      k(cat) and K(m) for CB1954 are about 20-fold higher than previously estimated;
      however, the measured specificity constant, k(cat)/K(m) is the same. All of the
      mutants are more active with CB1954 than the wild-type enzyme, the most active
      mutant showing about 100-fold improved specificity constant with CB1954 over the
      wild-type protein with little effect on k(cat). This enhancement in specificity
      constants for the mutants is not seen with the antibiotic nitrofurazone as
      substrate, leading to reversed nitroaromatic substrate selectivity for the double
      and triple mutants. However, similar enhancements in specificity constants are
      found with the quinone menadione. Stopped-flow kinetic studies suggest that the
      rate-determining step of the reaction is likely to be the release of products.
      The most active mutant is also selective for the 4-nitro group of CB1954, rather
      than the 2-nitro group, giving the more cytotoxic reduction product. The double
      and triple mutants should be much more effective enzymes for use with CB1954 in
      prodrug-activation gene therapy.

PMID- 19580257
TI  - Access to flavones via a microwave-assisted, one-pot Sonogashira-carbonylation
      annulation reaction.
AB  - Palladium complexes of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6
      phosphaadamantane are shown to be effective catalytic systems facilitating the
      sequential application of a microwave-assisted Sonogashira and carbonylative
      annulation reaction for the preparation of substituted flavones.

PMID- 19580256
TI  - Postsynthetic modification: a versatile approach toward multifunctional metal
      organic frameworks.
AB  - An isoreticular metal-organic framework (IRMOF-3) containing 2-amino-1,4
      benzenedicarboxylic acid (NH(2)-BDC) as a building block is shown to undergo
      chemical modification with a diverse series of anhydrides and isocyanates. The
      modification of IRMOF-3 by these reagents has been evidenced by using a variety
      of methods, including NMR and electrospray ionization mass spectrometry, and the
      structural integrity of the modified MOFs has been confirmed by thermogravimetric
      analysis, powder X-ray diffraction, and gas sorption analysis. The results show
      that a variety of functional groups can be introduced onto the MOF including
      amines, carboxylic acids, and chiral groups. Furthermore, it is shown that tert
      butyl-based asymmetric anhydrides can be used to selectively deliver chemical
      payloads to the IRMOF. Finally, the results demonstrate that at least four
      different chemical modifications can be performed on IRMOF-3 and that the
      reaction conditions can be modulated to control the relative abundance of each
      group. The findings presented here demonstrate several important features of
      postsynthetic modification on IRMOF-3, including (1) facile introduction of a
      wide range of functional groups using simple reagents (e.g., anhydrides and
      isocyanates), (2) the introduction of multiple (as many as four different)
      substituents into the MOF lattice, and (3) control over reaction conditions to
      preserve the crystallinity and microporosity of the resultant MOFs. The findings
      clearly illustrate that postsynthetic modification represents a powerful means to
      access new MOF compounds with unprecedented chemical complexity, which may serve
      as the basis of multifunctional materials.

PMID- 19580258
TI  - Asymmetric desymmetrization of 4,5-epoxycyclohex-1-ene by enantioselective
      allylic oxidation.
AB  - Asymmetric desymmetrization of allylic oxidation of 4,5-epoxycyclohex-1-ene (1)
      took place in the presence of 2.5 mol % of Cu(CH(3)CN)(4)PF(6) and 3 mol % of
      chiral N,N-bidentate ligand (S)-2 to afford (3S,4S,5S)-3-benzoyloxy-4,5
      epoxycyclohex-1-ene (3) in 84% ee, which was increased up to >99% ee after
      recrystallization of 3-4'-nitrobenzoyloxy derivative 6. Optically pure 6 proved
      to be a key intermediate for enantioselective synthesis of O-protected 2
      deoxystreptamine (2-DOS) precursor 12.

PMID- 19580259
TI  - N-heterocyclic carbene-catalyzed cross-coupling of aldehydes with arylsulfonyl
      indoles.
AB  - 3-(1-Arylsulfonylalkyl)indoles as electrophiles in the N-heterocyclic carbene
      catalyzed umpolung reaction of aldehydes were realized for the first time. This
      intermolecular Stetter-type reaction features the commercially available catalyst
      and mild reaction conditions, providing alpha-(3-indolyl) ketone derivatives in
      high yields for a wide range of substrates.

PMID- 19580260
TI  - Antibody binding to a tethered vesicle assembly using QCM-D.
AB  - The bilayer-tethered vesicle assembly has recently been proposed as a biomimetic
      model membrane platform for the analysis of integral membrane proteins. Here, we
      explore the binding of antibodies to membrane components of the vesicle assembly
      through the use of quartz crystal microbalance with dissipation monitoring (QCM
      D). The technique provides a quantitative, label-free avenue to study binding
      processes at membrane surfaces. However, converting the signal generated upon
      binding to the actual amount of antibody bound has been a challenge for a
      viscoelastic system such as the tethered vesicle assembly. In this work, we first
      established an empirical relationship between the amount of bound antibody and
      the corresponding QCM-D response. Then, the results were examined in the context
      of an existing model describing the QCM-D response under a variety of theoretical
      loading conditions. As a model system, we investigated the binding of monoclonal
      antidinitrophenyl (DNP) IgG(1) to tethered vesicles displaying DNP hapten groups.
      The measured frequency and dissipation responses upon binding were compared to an
      independent measure of the amount of bound antibody obtained through the use of
      an in situ ELISA assay. At saturation, the surface mass density of bound antibody
      was approximately 900 ng/cm(2). Further, through the application of QCM-D models
      that describe the response of the quartz when loaded by either a single
      homogeneous viscoelastic film or by a two-layered viscoelastic film, we found
      that a homogeneous, one-layer model accurately predicts the amount of antibody
      bound to the tethered vesicles near antibody surface saturation, but a two-layer
      model must be invoked to accurately describe the kinetic response of the
      dissipation factor, which suggests that the binding of the antibody results in a
      stiffening of the top layer of the film.

PMID- 19580261
TI  - Energy localization in molecules, bifurcation phenomena, and their spectroscopic
      signatures: the global view.

PMID- 19580263
TI  - Photoelectron spectroscopy of lanthanide-silicon cluster anions LnSi(n)(-) (3
      <or= n <or= 13; Ln = Ho, Gd, Pr, Sm, Eu, Yb): prospect for magnetic silicon-based
      clusters.
AB  - Photoelectron spectroscopy was utilized to study a variety of LnSi(n)(-) cluster
      anions (Ln = Yb, Eu, Sm, Gd, Ho, Pr; 3 <or= n <or= 13). For a particular size n,
      the measured valence electronic transitions of all these systems fall into either
      one of two categories, reflecting the influence of the different oxidation states
      of the lanthanide atoms involved. In one, the spectra of YbSi(n)(-) and EuSi(n)(
      ) are nearly identical to each other, while in the other the spectra of GdSi(n)(
      ), HoSi(n)(-), and PrSi(n)(-) are essentially identical. SmSi(n)(-) clusters
      exhibit an intermediate behavior with smaller clusters resembling the former
      category and larger clusters resembling the latter category. In the intermediate
      size range, 7 <or= n <or= 10, for SmSi(n)(-) both categories appear to be
      present, with one matching the EuSi(n)(-)-like systems and the other HoSi(n)(-)
      like clusters. The distinction between LnSi(n)(-) categories strongly correlates
      with the oxidation state of the particular lanthanide as usually found in its
      compounds. On the basis of this observation, we conclude that, among the Ln
      silicon clusters studied herein, Yb, Eu, and in case of Sm, sizes n >or= 10,
      adopt a nominal +2 oxidation state while Ho, Pr, Gd, and in case of Sm, sizes n
      <or= 7, exhibit a nominal +3 oxidation state. Furthermore, dramatic increases in
      adiabatic electron affinity values observed at n = 10 for the Ln(III)Si(n) series
      and at n = 12 for the Ln(II)Si(n) series were attributed to an inherent
      electronic stabilization of those particular clusters, rather than to the
      lanthanides' encapsulation. The observed limited effect of f-electrons on the
      valence electronic structure and thus on bonding in LnSi(n)(-) clusters may leave
      these electrons available for inducing magnetism. Consequently, Ln@Si(n) clusters
      may hold promise as building blocks of silicon-based cluster materials with
      magnetic properties.

PMID- 19580262
TI  - The medicinal applications of imidazolium carbene-metal complexes.

PMID- 19580266
TI  - (E)-2-boryl-1,3-butadiene derivatives of the 10-TMS-9-BBDs: highly selective
      reagents for the asymmetric synthesis of anti-1,2-disubstituted 3,4-pentadien-1
      ols.
AB  - The efficient stepwise construction of optically pure trans-4-substituted 2-boryl
      1,3-butadienes 6 is described. Hydroboration of 1-alkynes with either
      enantiomeric form of 3 leads to the pure trans-1-alkenylboranes 4 which undergo
      addition of alpha-ethoxyvinyllithium followed by a BF(3)-mediated 1,2-B-->C
      vinylic group migration to provide 6. These organoboranes 6 serve as a new type
      of asymmetric allylborating agent providing an extremely selective protocol for
      the preparation of anti-1,2-disubstituted 3,4-pentadien-1-ols 8 as essentially
      single diastereomers in enantiomerically pure form. One example of a cis-2-boryl
      1,3-butadiene (9) was prepared through a Grignard procedure. It was found to
      provide the corresponding syn-alcohol 11. The utility of 8 was demonstrated in
      their conversion to substituted beta-hydroxy acids 12 through ozonolysis and to
      substituted alpha,beta-unsaturated-delta-lactones 13 through Ru-catalyzed
      cyclocarbonylation.

PMID- 19580264
TI  - An alpha/beta-peptide helix bundle with a pure beta3-amino acid core and a
      distinctive quaternary structure.
AB  - Helix bundles are among the most widely studied tertiary and quaternary
      structural motifs in proteins. Here we present the crystal structure of an
      alpha/beta-peptide foldamer that adopts a tetrameric helix-bundle quaternary
      structure with a hydrophobic core composed solely of beta-amino acids. The
      structure displays features that are unprecedented among all known helix bundles
      composed of either alpha-peptides or peptidic foldamers. The tetramer is
      characterized by an asymmetry of interaction between neighboring helices, and the
      side-chain packing within the hydrophobic core differs fundamentally from the
      knobs-into-holes arrangement typical of most helix bundles.

PMID- 19580267
TI  - Conjugation of colloidal clusters and chains by capillary condensation.
AB  - Capillary condensation was used to establish connections in colloidal clusters
      and 1D colloidal chains with high regional selectivity. This vapor-phase process
      produced conjugated clusters and chains with anisotropic functionality. The
      capillary condensation method is simple and can be applied to a wide range of
      materials. It can tolerate geometric variations and even permits conjugation of
      spatially separated particles. The selective deposition was also used to modulate
      the functionality on the colloid surfaces, producing tip-tethered nanosized
      building blocks that may be suitable for further assembly via directional
      interactions.

PMID- 19580268
TI  - Solvothermal reduction of chemically exfoliated graphene sheets.
AB  - We have developed a solvothermal reduction method that affords more effective
      reduction of chemically derived graphene sheets and graphite oxide than low
      temperature reduction methods. Solvothermal reduction removed oxygen and defects
      from graphene sheets, increased the size of sp(2) domains, and produced materials
      that were as conducting as pristine graphene and exhibited clear intrinsic Dirac
      behavior.

PMID- 19580269
TI  - Synthesis and spectroscopic studies on azo-dye derivatives of polymetallic
      lanthanide complexes: using diazotization to link metal complexes together.
AB  - Heteronuclear tetrametallic lanthanide complexes have been synthesized from
      stable complexes by diazotization and azo-compound formation. Luminescence
      spectroscopy has been used to show that the complexes used as building blocks are
      stable under the reaction conditions.

PMID- 19580270
TI  - A free energy pathway for the interaction of the SRY protein with its binding
      site on DNA from atomistic simulations.
AB  - The SRY gene on the Y chromosome is a necessary and sufficient condition for the
      development of the male phenotype and is involved in sex-reversal pathologies.
      The associated SRY protein also represents a convenient model system for the
      study of indirect protein-DNA recognition mechanisms, in which the local
      plasticity of DNA may play a more important role than direct interactions between
      the protein and the DNA bases. Using a novel, low-bias restraint methodology, we
      have performed molecular dynamics simulations of the controlled dissociation of
      SRY from its cognate DNA sequence. The resulting free energy profile provides a
      detailed view of protein-DNA binding and identifies a metastable intermediate
      state.

PMID- 19580271
TI  - Characterization of water wires inside hydrophobic tubular peptide structures.
AB  - The crystallographic observation of a hydrophobic, empty channel (diameter
      approximately 5.2 A) in the peptide Boc-(D)Pro-Aib-Leu-Aib-Val-OMe, prompted the
      investigation of the analog Boc-(D)Pro-Aib-Val-Aib-Val-OMe in which the side
      chain at position 3 was shortened, resulting in the structure of a channel
      (diameter approximately 7.5 A) containing a one-dimensional wire of water
      molecules. Crystallization in the space group P6(5) facilitates formation of a
      pore lined entirely by hydrocarbon side chains. Two forms of the entrapped water
      wires, with O...O separations of 3.5 and 2.6 A, are discussed. A lone hydrogen
      bond between the adjacent pairs of water molecules in the wire, with no strong
      interactions between the second water hydrogen and the hydrophobic walls of the
      channel, is a feature of the one-dimensional array. The structure provides the
      first crystallographic characterization of a water wire in a hydrophobic channel
      with implications in water and proton transport in membranes and carbon
      nanotubes.

PMID- 19580272
TI  - Quasi-2D XY magnetic properties and slow relaxation in a body centered metal
      organic network of [Co4] clusters.
AB  - Octahedral Co(2+) centers have been connected by mu(3)-OH and mu(2)-OH(2) units
      forming [Co(4)] clusters which are linked by pyrazine forming a two-dimensional
      network. The two-dimensional layers are bridged by oxybisbenzoate (OBA) ligands
      giving rise to a three-dimensional structure. The [Co(4)] clusters bond with the
      pyrazine and the OBA results in a body-centered arrangement of the clusters,
      which has been observed for the first time. Magnetic studies reveal a
      noncollinear frustrated spin structure of the bitriangular cluster, resulting in
      a net magnetic moment of 1.4 microB per cluster. For T > 32 K, the correlation
      length of the cluster moments shows a stretched-exponential temperature
      dependence typical of a Berezinskii-Kosterlitz-Thouless model, which points to a
      quasi-2D XY behavior. At lower temperature and down to 14 K, the compound behaves
      as a soft ferromagnet and a slow relaxation is observed, with an energy barrier
      of ca. 500 K. Then, on further cooling, a hysteretic behavior takes place with a
      coercive field that reaches 5 T at 4 K. The slow relaxation is assigned to the
      creation/annihilation of vortex-antivortex pairs, which are the elementary
      excitations of a 2D XY spin system.

PMID- 19580274
TI  - Chalcogenide chemistry in ionic liquids: nonlinear optical wave-mixing properties
      of the double-cubane compound [Sb7S8Br2](AlCl4)3.
AB  - The new cation [Sb(7)S(8)Br(2)](3+) has a double-cubane structure and forms as
      the [AlCl(4)](-) salt from the ionic liquid EMIMBr-AlCl(3) (EMIM = 1-ethyl-3
      methylimidazolium) at 165 degrees C. The compound is noncentrosymmetric with
      space group P2(1)2(1)2(1) and exhibits second-harmonic and difference-frequency
      nonlinear optical response across a wide range of the visible and near-infrared
      regions.

PMID- 19580273
TI  - Palladium-catalyzed enantioselective alpha-arylation and alpha-vinylation of
      oxindoles facilitated by an axially chiral P-stereogenic ligand.
AB  - The enantioselective alpha-arylation and alpha-vinylation of oxindoles catalyzed
      by Pd and a biarylmonophosphine ligand with both axial and phosphorus-based
      chirogenicity is reported. The resultant quaternary carbon stereocenters are
      formed in high enantiomeric excess, and the conditions tolerate a range of
      substitution on both the oxindole and the aryl/vinyl coupling partners.

PMID- 19580275
TI  - What is the rate of the Csp2-Csp2 reductive elimination step? Revealing an
      unusually fast Ni-catalyzed Negishi-type oxidative coupling reaction.
AB  - For a direct quantitative investigation of the Csp(2)-Csp(2) reductive
      elimination rate within a catalytic cycle, a novel oxidative coupling system in
      the presence of a Ni catalyst and desyl chloride as the oxidant is devised. The
      reaction progress profiles of arylzinc reagents exhibit zero-order kinetic
      behavior, and a reductive elimination step is confirmed as the rate-determining
      step. This allows direct measurement of the Csp(2)-Csp(2) reductive elimination
      rate constant within a catalytic cycle. The rate constants of p-MePhZnCl are
      obtained in the range 0.23 to 3.5 s(-1) from 0 to -35 degrees C, which are
      unusually fast reaction rates. According to the Arrhenius equation, the values of
      DeltaH(double dagger) and DeltaS(double dagger) (DeltaH(double dagger) = 9.7 kcal
      mol(-1), DeltaS(double dagger) = 35 J mol(-1) K(-1)) are obtained. The small
      value of DeltaH(double dagger) reveals that the reductive elimination step of
      Csp(2)-Ni-Csp(2) is an extremely facile process.

PMID- 19580276
TI  - 15N-1H scalar coupling perturbation: an additional probe for measuring structural
      changes due to ligand binding.
AB  - Chemical shift perturbation mapping of backbone amides is one of the most widely
      employed techniques in biomolecular NMR, providing residue-by-residue information
      on interaction interfaces, ligand binding, and chemical modification sites, even
      for samples where poor solubility, short lifetime, or large size precludes more
      sophisticated experimental approaches. Significant changes can also occur in the
      amide one-bond (15)N-(1)H scalar coupling constants for glutamine binding protein
      (GlnBP) due to ligand binding. Like chemical shift perturbations, large changes
      (>1 Hz) are seen near the site of glutamine binding, though perturbations also
      occur distant to the site. The coupling constant perturbations correlate with
      significant structural changes, especially changes in backbone hydrogen bonding.
      Thus, amide scalar coupling perturbation can serve as an adjunct to chemical
      shift perturbation, providing additional information on both short-range and
      longer-range, allosteric structural changes.

PMID- 19580277
TI  - Pd(0)/PR3-catalyzed intermolecular arylation of sp3 C-H bonds.
AB  - Pd(0)-catalyzed intermolecular arylation of sp(3) C-H bonds has been achieved
      using PR(3)/ArI. This protocol can be used to arylate a variety of aliphatic
      carboxylic acid derivatives, including a number of bioactive drug molecules. The
      use of fluorinated aryl iodides also allows for the introduction of fluorine into
      a molecule of interest.

PMID- 19580278
TI  - Control of the molecular orientation of membrane-anchored biomimetic
      glycopolymers.
AB  - Quantifying and controlling the orientation of surface-bound macromolecules is
      crucial to a wide range of processes in areas as diverse as biology, materials
      science, and nanotechnology. Methods capable of directing orientation, as well as
      an understanding of the underlying physical mechanisms are, however, lacking. In
      this paper, we describe experiments in which the conformations of structurally
      well-defined polymers anchored to fluid lipid membranes were probed using
      Fluorescence Interference Contrast Microscopy (FLIC), an optical technique that
      provides topographic information with few-nanometer precision. The novel rodlike
      polymers mimic the architecture of mucin glycoproteins and feature a phospholipid
      tail for membrane incorporation and a fluorescent optical probe for FLIC imaging
      situated at the opposite termini of the densely glycosylated polymeric backbones.
      We find that the orientation of the rigid, approximately 30 nm long glycopolymers
      depends profoundly on the properties of the optical reporter. Molecules
      terminated with Alexa Fluor 488 projected away from the lipid bilayer by 11 +/- 1
      nm, consistent with entropy-dominated sampling of the membrane-proximal space.
      Molecules terminated with Texas Red lie flat at the membrane (height, 0 +/- 2
      nm), implying that interactions between Texas Red and the bilayer dominate the
      polymers' free energy. These results demonstrate the design of macromolecules
      with specific orientational preferences, as well as nanometer-scale measurement
      of their orientation. Importantly, they reveal that seemingly minute changes in
      molecular structure, in this case fluorophores that comprise only 2% of the total
      molecular weight, can significantly alter the molecule's presentation to the
      surrounding environment.

PMID- 19580279
TI  - Introduction of methionines in the gas channel makes [NiFe] hydrogenase aero
      tolerant.
AB  - Hydrogenases catalyze the conversion between 2H(+) + 2e(-) and H(2)(1). Most of
      these enzymes are inhibited by O(2), which represents a major drawback for their
      use in biotechnological applications. Improving hydrogenase O(2) tolerance is
      therefore a major contemporary challenge to allow the implementation of a
      sustainable hydrogen economy. We succeeded in improving O(2) tolerance, which we
      define here as the ability of the enzyme to resist for several minutes to O(2)
      exposure, by substituting with methionines small hydrophobic residues strongly
      conserved in the gas channel. Remarkably, the mutated enzymes remained active in
      the presence of an O(2) concentration close to that found in aerobic solutions in
      equilibrium with air, while the wild type enzyme is inhibited in a few seconds.
      Crystallographic and spectroscopic studies showed that the structure and the
      chemistry at the active site are not affected by the mutations. Kinetic studies
      demonstrated that the inactivation is slower and reactivation faster in these
      mutants. We propose that in addition to restricting O(2) diffusion to the active
      site of the enzyme, methionine may also interact with bound peroxide and provide
      an assisted escape route for H(2)O(2) toward the gas channel. These results show
      for the first time that it is possible to improve O(2)-tolerance of [NiFe]
      hydrogenases, making possible the development of biohydrogen production systems.

PMID- 19580280
TI  - Probing conformers and adsorption footprints at the single-molecule level in a
      highly organized amino acid assembly of (S)-proline on Cu(110).
AB  - Establishing the nanoscale details of organized amino acid assemblies at surfaces
      is a major challenge in the field of organic-inorganic interfaces. Here, we show
      that the dense (4 x 2) overlayer of the amino acid, (S)-proline on a Cu(110)
      surface can be explored at the single-molecule level by scanning tunneling
      microscopy (STM), reflection absorption infrared spectroscopy (RAIRS), and
      periodic density functional theory (DFT) calculations. The combination of
      experiment and theory, allied with the unique structural rigidity of proline,
      enables the individual conformers and adsorption footprints adopted within the
      organized assembly to be determined. Periodic DFT calculations find two
      energetically favorable molecular conformations, projecting mirror-image chiral
      adsorption footprints at the surface. These two forms can be experimentally
      distinguished since the positioning of the amino group within the pyrrolidine
      ring leads each chiral footprint and associated conformer to adopt very different
      ring orientations, producing distinct contrasts in the STM images. DFT modeling
      shows that the two conformers can generate eight possible (4 x 2) overlayers with
      a variety of adsorption footprint arrangements. STM images simulated for each
      structural model enables a direct comparison to be made with the experiment and
      narrows the (4 x 2) overlayer to one specific structural model in which the
      juxtaposition of molecules leads to the formation of one-dimensional hydrogen
      bonded prolate chains directed along the [110] direction.

PMID- 19580281
TI  - High-field EPR and magnetic susceptibility studies on binuclear and tetranuclear
      copper trifluoroacetate complexes. X-ray structure determination of three
      tetranuclear quinoline adducts of copper(II) trifluoroacetate.
AB  - Magnetic properties and high-field EPR spectra of three previously unknown
      tetranuclear quinoline adducts of copper(II) trifluoroacetate were studied, and
      their X-ray structures were determined. Two green complexes containing a mu(4)
      oxo bridge, Cu(4)O(CF(3)COO)(6)(quin)(4) x (C(6)H(5)CH(3))(0.6) (orthorhombic,
      Pbca, a = 15.278(3), b = 23.227(5), c = 34.895(7) A) and
      Cu(4)O(CF(3)COO)(6)(quin)(4) x (C(6)H(6))(0.8) (monoclinic, P2/c, a = 21.933(4),
      b = 11.176(2), c = 23.927(5) A, beta = 97.41(3) degrees) are ferromagnetic,
      whereas the blue complex [Cu(4)(OH)(2)(CF(3)COO)(8)(quin)(2)](2-)(quinH(+))(2)
      (monoclinic, a = 21.933(4), b = 11.176(2), c = 23.927(5) A, beta = 97.41(3)
      degrees), formed in humid air from the solid dimeric [Cu(CF(3)COO)(2) x
      (quin)](2), is antiferromagnetic, as is the tetranuclear blue product formed in
      humid air of the mu(4)-oxo tetramers. High-field EPR spectra allowed
      determination of the spin Hamiltonian parameters for the spin quintet state (S =
      2) in the ferromagnetic complexes, which facilitated accurate interpretation of
      their magnetic susceptibility data. "Broken symmetry" DFT calculations were
      performed to estimate the exchange integrals in all three tetranuclear complexes,
      showing surprisingly good agreement with experimental results. Negative sign of
      the zero-field splitting parameter D in two binuclear complexes, [Cu(CF(3)COO)(2)
      x CH(3)CN](2) and [Cu(CF(3)COO)(2) x (quin)](2), was found from single-crystal
      high-field EPR spectra, confirming recent results for nonhalogenated dimeric
      copper carboxylates.

PMID- 19580282
TI  - Importance of C-N bond rotation in N-acyl oxazolidinones in their SmI2-promoted
      coupling to acrylamides.
AB  - A detailed mechanistic investigation was undertaken to determine the dominating
      factors of the postelectron transfer steps in the SmI(2)-promoted carbon-carbon
      bond forming reaction between N-acyl oxazolidinones and acrylamides. Competition
      experiments were performed by reacting two N-acyl oxazolidinones with a limiting
      amount of N-t-butyl acrylamide, and from the product distribution, the relative
      reactivity values (RV) for a series of N-acyl oxazolidinones were then calculated
      against N-pivaloyl oxazolidinone as the reference. An almost linear correlation
      was obtained for the simple alkyl N-acyl oxazolidinones when ln RV was plotted
      against the activation barriers for C-N bond rotation (s-trans to s-cis) obtained
      by DFT calculations, implying that C-N bond rotation from the s-trans to s-cis
      conformation is one of the essential parameters controlling the reactivity. These
      results were substantiated by other competition experiments carried out for the
      corresponding imide derivatives, where rotation is not necessary for obtaining
      bidentate coordination and where no such correlation as described above was
      observable. The finding that the reactivity of the simple N-acyl oxazolidinones
      for these SmI(2)-mediated transformations correlates with the activation barriers
      for C-N bond rotation may have implications for other useful synthetic organic
      reactions involving similar substrates. Finally, these studies were extrapolated
      to understanding the poor reactivity of N-acyl oxazolidinones, as those derived
      from Evans chiral auxiliaries, with N-tert-butyl acrylamide. These couplings
      appear to be dominated by the activation energy for addition because of arising
      syn-pentane interactions in the transition-state for C-C bond formation. We
      demonstrate that the addition of Lewis acids can have a beneficial effect on the
      coupling yields.

PMID- 19580283
TI  - Interaction between phenolics and gut microbiota: role in human health.
AB  - Dietary phenolic compounds are often transformed before absorption. This
      transformation modulates their biological activity. Different studies have been
      carried out to understand gut microbiota transformations of particular polyphenol
      types and identify the responsible microorganisms. Although there are potentially
      thousands of different phenolic compounds in the diet, they are typically
      transformed to a much smaller number of metabolites. The aim of this review was
      to discuss the current information about the microbial degradation metabolites
      obtained from different phenolics and their formation pathways, identifying their
      differences and similarities. The modulation of gut microbial population by
      phenolics was also reviewed in order to understand the two-way phenolic
      microbiota interaction. Clostridium and Eubacterium genera, which are
      phylogenetically associated, are other common elements involved in the metabolism
      of many phenolics. The health benefits from phenolic consumption should be
      attributed to their bioactive metabolites and also to the modulation of the
      intestinal bacterial population.

PMID- 19580285
TI  - Spatial and temporal analysis of textural and biochemical changes of imported
      avocado cv. Hass during fruit ripening.
AB  - The ripeness degree of climacteric fruits, such as avocado ( Persea americana
      Mill.), can be correlated with rheological properties. However, there remains
      little information on not only the postharvest changes in texture of avocado
      fruit from different origins but also the spatial variation within fruit. In
      addition, the relationship between changes in texture and composition of fatty
      acids and major nonstructural carbohydrates (NSCs) of fruit tissue during
      ripening is unknown. The texture of different horizontally cut slices from
      individual fruits within a consignment was measured during ripening using a
      previously unreported technique. The composition of fatty acids and NSCs in fruit
      mesocarp tissue was determined. The composition of fatty acids and oil and dry
      matter contents varied significantly according to origin. Significant changes in
      texture, mannoheptulose and perseitol contents, and linoleic acid percentage were
      found in avocado fruit flesh during ripening. Spatial variation within fruit was
      detected in both textural and biochemical characteristics.

PMID- 19580284
TI  - Comparative analysis of flavonoid profile, antioxidant and antimicrobial activity
      of the berries of Juniperus communis L. var. communis and Juniperus communis L.
      var. saxatilis Pall. from Turkey.
AB  - The present study was designed to define and compare the flavonoid composition
      and the biological potential of berries methanol extracts of Juniperus communis
      L. var. communis (Jcc) and Juniperus communis L. var. saxatilis. Pall. (Jcs) from
      Turkey. Total polyphenols (Folin-Ciocalteau method) were 3-fold higher in Jcc
      (59.17 +/- 1.65 mg GAE/g extract) than in Jcs (17.64 +/- 0.09 mg GAE/g extract).
      Flavonoid and biflavonoid content, evaluated by HPLC-DAD-ESI-MS analysis, was
      higher in Jcc (25947 +/- 0.86 and 4346 +/- 3.95 microg/g extract) than in Jcs
      (5387 +/- 34.88 and 1944 +/- 26.88 microg/g extract). The HPLC analysis of Jcc
      allowed the separation of 16 flavonoids; hypolaetin-7-pentoside and quercetin
      hexoside are the main compounds. Moreover, gossypetin-hexoside-pentoside and
      gossypetin-hexoside were identified for the first time in Jcc berries. In Jcs
      eight flavonoids were identified: quercetin-hexoside and isoscutellarein-8-O
      hexoside are the most abundant compounds. The in vitro antioxidant activity was
      determined using different methods; Jcc was found to be more active than Jcs in
      the DPPH test (IC(50) of 0.63 +/- 0.09 mg/mL and 1.84 +/- 0.10 mg/mL) in reducing
      power assay (12.82 +/- 0.10 ASE/mL and 64.14 +/- 1.20 ASE/mL), and in TBA assay
      (IC(50) of 4.44 +/- 0.70 microg/mL and 120.07 +/- 3.60 microg/mL). By contrast,
      Jcs exhibited more elevated Fe(2+) chelating ability than Jcc. The extracts were
      also studied for their antimicrobial potential, displaying antimicrobial capacity
      only against Gram-positive bacteria.

PMID- 19580286
TI  - Nucleoside-5'-monophosphates as prodrugs of adenosine A2A receptor agonists
      activated by ecto-5'-nucleotidase.
AB  - Prodrugs of adenosine A(2A) receptor agonists were developed that are activated
      by ecto-5'-nucleotidase (ecto-5'-NT, CD73). Because ecto-5'-NT is upregulated in
      inflamed tissue, the A(2A) agonists are expected to be released from their
      prodrug form at the sites of inflammation. 2-(Ar)alkyl-substituted AMP
      derivatives were synthesized and investigated. Certain 2-substituted AMP
      derivatives, including 2-hexylthio-AMP, 2-cyclopentylthio-AMP, 2
      cyclohexylmethylthio-AMP, and 2-cyclohexylethylthio-AMP were accepted as
      substrates by ecto-5'-NT and readily converted to the corresponding 2-substituted
      adenosine derivatives. The 2-cyclohexylethylthio substitution was a good
      compromise between the requirements of the ecto-5'-NT and the adenosine A(2A)
      receptor. The corresponding AMP derivative (12g) was a similarly good substrate
      as AMP itself, while the resulting adenosine derivative (11g) was a relatively
      potent A(2A) agonist (radioligand binding to rat brain striatal membranes: K(i) =
      372 nM; inhibition of anti-CD3/anti-CD28-induced IFN-gamma release in mouse CD4+
      cells: EC(50) = 50 nM). Compound 11g was released from 12g by incubation with
      CD4+ cells isolated from wild-type mice but only to a much smaller extent by
      cells from ecto-5'-NT knockout mice. Compound 12g will be a new lead structure
      for the development of more potent and selective ecto-5'-NT-activated prodrugs of
      selective anti-inflammatory A(2A) receptor agonists.

PMID- 19580287
TI  - Carbonic anhydrase-encoded dynamic constitutional libraries: toward the discovery
      of isozyme-specific inhibitors.
AB  - A constitutional dynamic library (CDL) was generated under thermodynamic control
      by using the amino-carbonyl/imine interconversion as reversible chemistry,
      combined with noncovalent bonding within the active site of the metalloenzyme
      carbonic anhydrase (CA, EC 4.2.1.1). Considering the pharmacological importance
      to find isoform-selective CA inhibitors (CAIs), two of the 15 human (h) isoform,
      i.e., hCAI and hCA II, have been subjected to a parallel screening of the same
      CDL. The use of parallel constitutional screening of CDL chemistry for the
      discovery of enzyme inhibitors is straightforward and it might provide initial
      insights toward the generation of efficient classes of selective, high affinity
      inhibitors. We demonstrate here that the high selectivity and specificity of
      inhibiting the hCA I and hCA II isozymes with some of the detected hits may be
      used to describe a complex constitutional behavior through component selection
      from the dynamic library, driven by the selective binding to the specific isoform
      active site. These results also point to the possibility of modulating the drug
      discovery methods by constitutional recomposition induced by a specific enzymatic
      target.

PMID- 19580290
TI  - Role of vapor-phase mass transport during the spreading of a long-chain alkane
      drop.
AB  - The spreading of liquid alkanes over solid surfaces has important applications in
      painting, coatings, lubrication, and petroleum tertiary recovery. The role of the
      vapor-phase mass transport accompanying liquid spreading has not been well
      studied because it is difficult to separate the contributions from the liquid
      spreading and the vapor-phase transport that occurred at the same time. We used
      the engineered surface patterns to study the vapor-phase mass transport during
      liquid spreading. First, we fabricated several hydrophilic, carboxylic acid
      terminated patterns (OTSpd) on a hydrophobic, methyl-terminated
      octadecyltrichlorosilane (OTS) surface. These OTSpd patterns did not connect to
      each other. Next, we let an alkane drop spread within one OTSpd pattern. The
      liquid alkane could not spread to other OTSpd patterns because OTS separated
      them; however, the alkane molecules in the vapor phase could migrate and adsorb
      on other OTSpd patterns. Therefore, the contributions from the liquid spreading
      and the vapor-phase transport were separated and could be investigated
      independently. We found that during the spreading of the liquid alkane, mass
      transport through the vapor phase cannot be ignored. Alkane molecules adsorbed on
      the OTSpd surface with their backbones parallel to the surface in the first few
      layers. Additional alkane molecules adsorbed on these parallel layers to form the
      seaweed-shaped layers in which the alkane molecules stood up. Our study showed
      that the parallel layers formed from the vapor-phase mass transport before the
      liquid alkane spread. Therefore, the liquid alkane does not spread over the more
      strongly binding OTSpd surface. It actually spreads over the parallel alkane
      layer, which formed from its own vapor.

PMID- 19580288
TI  - Magnetic resonance molecular imaging of vascular cell adhesion molecule-1
      expression in inflammatory lesions using a peptide-vectorized paramagnetic
      imaging probe.
AB  - The vascular cell adhesion molecule-1 (VCAM-1) has distinct roles in inflammatory
      cell recruitment to the damaged vessel wall. In the present work, a cyclic
      heptapeptide phage displayed library was screened in vitro during four rounds of
      biopanning. On the basis of Kd and IC50 values, a peptide (encoded as R832) was
      selected for in vitro and in vivo validation. After conjugation to Gd-DOTA, VCAM
      1 imaging was assessed by MRI on a model of T cell mediated hepatitis, induced in
      mice by concanavalin A. On histological samples, the location of biotinylated
      R832 (R832-Bt) around liver veins in hepatitis resembles the pattern of MRI
      enhancement. Gd-DOTA-R832 was then assessed on ApoE(-/-) mice and produced an
      important signal enhancement of the aortic wall, while R832-Bt interacted with
      morphologic structures comparable to those marked by anti-VCAM-1 antibody. In
      conclusion, the in vitro and in vivo evaluation of peptide R832 suggests a
      specific interaction with the targeted biomolecule. Its conjugation to imaging
      reporters could assist the diagnosis of inflammatory diseases.

PMID- 19580292
TI  - Statistical total correlation spectroscopy editing of 1H NMR spectra of
      biofluids: application to drug metabolite profile identification and enhanced
      information recovery.
AB  - Here we present a novel method for enhanced NMR spectral information recovery,
      utilizing a statistical total correlation spectroscopy editing (STOCSY-E)
      procedure for the identification of drug metabolite peaks in biofluids and for
      deconvolution of drug and endogenous metabolite signals. Structurally correlated
      peaks from drug metabolites and those from closely related drug metabolite
      pathways are first identified using STOCSY. Subsequently, this correlation
      information is utilized to scale the biofluid (1)H NMR spectra across these
      identified regions, producing a modified set of spectra in which drug metabolite
      contributions are reduced and, thus, facilitating analysis by pattern recognition
      methods without drug metabolite interferences. The application of STOCSY-E is
      illustrated with two exemplar (1)H NMR spectroscopic data sets, posing various
      drug metabolic, toxicological, and analytical challenges viz. 800 MHz (1)H
      spectra of human urine (n = 21) collected over 10 h following dosing with the
      antibiotic flucloxacillin and 600 MHz (1)H NMR spectra of rat urine (n = 27)
      collected over 48 h following exposure to the renal papillary toxin 2
      bromoethanamine (BEA). STOCSY-E efficiently identified and removed the major
      xenobiotic metabolite peaks in both data sets, providing enhanced visualization
      of endogenous changes via orthogonal to projection filtered partial least-squares
      discriminant analysis (OPLS-DA). OPLS-DA of the STOCSY-E spectral data from the
      BEA-treated rats revealed the gut bacterial-mammalian co-metabolite
      phenylacetylglycine as a previously unidentified surrogate biomarker of toxicity.
      STOCSY-E has a wide range of potential applications in clinical, epidemiology,
      toxicology, and nutritional studies where multiple xenobiotic metabolic
      interferences may confound biological interpretation. Additionally, this tool
      could prove useful for applications outside of metabolic analysis, for example,
      in process chemistry for following chemical reactions and equilibria and
      detecting impurities.

PMID- 19580295
TI  - IBS-catalyzed oxidative rearrangement of tertiary allylic alcohols to enones with
      oxone.
AB  - A 2-iodoxybenzenesulfonic acid (IBS)-catalyzed oxidative rearrangement of
      tertiary allylic alcohols to enones with powdered Oxone in the presence of
      potassium carbonate and tetrabutylammonium hydrogen sulfate has been developed.

PMID- 19580294
TI  - Synthesis of (S)-imperanene by using allylic substitution.
AB  - Synthesis of (S)-imperanene (1) was studied by using copper-assisted allylic
      substitution of ArCH=CHCH(L)CH(2)Ar (L: leaving group) and (i
      PrO)Me(2)SiCH(2)MgCl. Preliminary substitution between PhCH=CHCH(L)Me (L = AcO,
      PivO, MeOCO(2), (2-Py)CO(2)) and Bu copper reagents derived from BuMgX (X = Br,
      Cl) and CuBr.Me(2)S or CuCl in 1:1-40:1 ratios suggested acetate 28 as the best
      substrate. To prepare 28, kinetic resolution of racemic (E)
      TMSCH=CHCH(OH)CH(2)Ar(2) (Ar(2) = (p-TBSO)(m-MeO)C(6)H(3)) carried out by using
      the asymmetric epoxidation with (-)-DIPT afforded the corresponding epoxy alcohol
      and (S)-allylic alcohol. After separation by chromatography, these products were
      converted to (S,E)-Bu(3)SnCH=CHCH(OH)CH(2)Ar(2), which upon palladium-catalyzed
      coupling with Ar(2)-I followed by acetylation gave 28 (95-98% ee). Substitution
      of 28 with (i-PrO)Me(2)SiCH(2)MgCl and CuBr.Me(2)S in a 4:1 ratio at 0 degrees C
      proceeded cleanly to produce 29 with 100% inversion in 92% yield. Finally, Tamao
      oxidation furnished 1.

PMID- 19580296
TI  - Interplay between solvent effects of different nature in interfacial bond
      breaking electron transfer.
AB  - Solvent dynamics effects on electroreduction of peroxodisulphate anion on mercury
      electrode (a typical bond breaking electron transfer reaction) are explored in
      the framework of the Sumi-Marcus model. The reaction three-dimensional free
      energy surface is constructed using the Anderson model Hamiltonian. A new
      interpretation of short- and long-time survival times is presented as well. Since
      the reduction is assumed to proceed from aqueous sucrose and glucose solutions of
      different concentrations (which are used to vary the solution viscosity),
      unavoidable changes in the Pekar factor (static effect) are also taken into
      account. The results of model calculations are employed to interpret challenging
      experimental data on nonmonotonous constant rate vs solution viscosity dependence
      reported earlier (in part, appearance of an ascent plot). The influence of mixed
      solvent composition on the reaction rate and transfer coefficient is explained in
      terms of the saddle point avoidance in the vicinity of activationless discharge.
      Splitting of the reaction coordinates into slow (solvent) and fast
      (intramolecular) ones is argued to be crucial, as the most important reaction
      features cannot be described by means of more simplified models, even if both
      static and dynamic effects are addressed.

PMID- 19580297
TI  - Phosphine-mediated olefination between aldehydes and allenes: an efficient
      synthesis of trisubstituted 1,3-dienes with high E-selectivity.
AB  - The phosphine-mediated olefination of aldehydes with electron-deficient allenes
      to afford trisubstituted conjugated dienes in fair to excellent yields with high
      E-selectivity is described. The reaction represents a new reactivity pattern of
      allenes with aldehydes and also provides a highly stereoselective synthetic
      method for preparing conjugated dienes. In the reaction, the phosphine acts as a
      nucleophilic promoter to generate in situ an active phosphorus ylide which
      mediates the intermolecular olefination.

PMID- 19580298
TI  - Refractive index control and Rayleigh scattering properties of transparent TiO2
      nanohybrid polymer.
AB  - The surface of TiO2 nanoparticles (NPs) was modified by a coupling agent of 2
      (3,4-epoxycyclohexyl)ethyltrimethoxysilane to render them highly compatible with
      organic monomer mixtures avoiding aggregation. Such TiO2 NPs were then chemically
      attached with a prepolymer. The refractive index of hybrid TiO2 NPs-polymer was
      increased dramatically in comparison with that of pure polymer, and it can be
      controlled by adjusting the content of TiO2 NPs. The Rayleigh scattering of
      hybrid TiO2 NPs-polymer was size-dependent and increased with the increase of the
      TiO2 NPs content. When Rayleigh scattering of the hybrid material prepared with a
      milling and centrifuge process was significantly lowered, one can obtain a
      transparent sample, which is good for optical devices.

PMID- 19580299
TI  - Theoretical study of dioxygen induced inhibition of [FeFe]-hydrogenase.
AB  - Hydrogenases comprise a variety of enzymes that catalyze the reversible oxidation
      of molecular hydrogen. Out of this group, [FeFe]-hydrogenase shows the highest
      activity for hydrogen production which is, therefore, of great interest in the
      field of renewable energies. Unfortunately, this comes with the flaw of a
      generally very high sensitivity against molecular oxygen that irreversibly
      inhibits this enzyme. While many studies have already addressed the mechanism of
      hydrogen formation by [FeFe]-hydrogenase, little is known about the molecular and
      mechanistic details leading to enzyme inactivation by O(2). In order to elucidate
      this process, we performed density functional theory calculations on several
      possible O(2) adducts of the catalytic center--the so-called H-cluster--and show
      that the direct interaction of the [2Fe](H) subsite with dioxygen is an
      exothermic and specific reaction in which O(2) most favorably binds in an end-on
      manner to the distal Fe(d). Based on the results, we propose a protonation
      mechanism that can explain the irreversibility of dioxygen-induced enzyme
      inactivation by water release and degradation of the ligand environment of the H
      cluster.

PMID- 19580300
TI  - The infrared spectra of the retinal chromophore in bacteriorhodopsin calculated
      by a DFT/MM approach.
AB  - In the preceding paper (DOI 10.1021/jp902428x), we have derived the polarized
      force field "PBR" for bacteriorhodopsin (BR) using hybrid methods which combine
      density functional theory (DFT) with molecular mechanics (MM) models. This
      polarized force field has enabled extended molecular dynamics (MD) simulations of
      BR's chromophore binding pocket which closely preserve the experimentally well
      known structure. Here, we employ the PBR-MD trajectories obtained for the
      conformational substates prevalent at physiological temperatures as material for
      the DFT/MM computation of the chromophore's vibrational spectra. By comparison
      with DFT results on the structure and vibrational spectra of an isolated
      chromophore, we identify the structural and spectral changes induced by the
      protein environment. Comparisons with the wealth of experimental data available
      in the literature on the chromophore's vibrational spectra yield estimates on the
      accuracy of the DFT/MM descriptions. We discuss why highly accurate DFT/MM
      descriptions are expected to become a decisive tool for solving the long-standing
      enigma of how the light-driven proton pump BR actually works.

PMID- 19580301
TI  - Conformation switching in gas-phase complexes of histidine with alkaline earth
      ions.
AB  - Infrared multiple photon dissociation spectroscopy of gas-phase doubly charged
      alkaline earth complexes of histidine reveals a transition from dominance of the
      zwitterion (salt bridge, SB) conformation with Ba2+ to substantial presence of
      the canonical (charge-solvated, CS) conformation with Ca2+. This result is a
      clear illustration of the importance of metal-ion size in governing the delicate
      balance between these two modes of complexation of gas-phase amino acids. The two
      conformational motifs are clearly distinguished by characteristic spectral
      features, confirmed by density functional theory simulated IR spectra of the low
      energy conformers. As a further illustration of histidine complexation
      possibilities, the spectrum of the Na+His complex shows purely CS character and
      emphasizes the greater tendency toward SB character induced by the higher charge
      in the alkaline earth complexes. Calculation of the complete series of alkaline
      earth/histidine complexes confirms the increasing stability of the SB
      conformations relative to CS with increasing metal ion size, as well as showing
      that among SB conformations the most highly chelated conformation (SB3) is
      favored for small metals, whereas the most extended conformation (SB1) is favored
      for large metals. A decomposition of the binding thermochemistry shows that these
      thermochemical trends versus metal-ion size are due to differences in
      electrostatic binding energies, with relatively little contribution from the
      deformation and rearrangement energy costs of distorting the ligand framework.

PMID- 19580302
TI  - Effects of various small-molecule anesthetics on vesicle fusion: a study using
      two-photon fluorescence cross-correlation spectroscopy.
AB  - Currently, the molecular mechanism for membrane fusion remains unconfirmed. The
      most compelling suggested mechanism is the stalk hypothesis, which states that
      membrane fusion proceeds via stalk formation/hemifusion, among other steps.
      Because the stalk would have a very high radius of curvature, small lipophilic
      molecules could enhance fusion by lowering the energy barrier to stalk formation.
      We previously showed that the general anesthetic halothane is capable of inducing
      membrane fusion in 1,2-dileoyl-sn-3-glycero-3-phospocholine (DOPC) vesicles. In
      the present study, we examined other small molecules, general anesthetics
      (chloroform, isoflurane, enflurane, and sevoflurane), to determine whether they
      exhibit fusion properties with model lipid membranes similar to those of
      halothane. We employed both two-photon excitation fluorescence cross-correlation
      spectroscopy (TPE-FCCS) and steady-state fluorescence dequenching (FD) assays.
      Using volatile general anesthetics as novel fusion agents, we also aimed to gain
      a better understanding of the membrane fusion mechanism at a molecular level. We
      found that lipid mixing or lipid rearrangement, which is required for the
      formation of the fusion-state intermediates and the fusion pore, rather than the
      association of lipid vesicles, is rate-limiting. In addition, halothane and
      chloroform were found to induce lipid mixing (rearrangement) to a greater extent
      than isoflurane, enflurane, and sevoflurane. Finally, it is proposed that the
      efficiency of these general anesthetics as fusion agents is related to their
      partition coefficients, water solubilities, polarities, and molecular volumes,
      all of which affect the ability of each anesthetic to perturb the contacting
      bilayer membranes of fusing vesicles.

PMID- 19580303
TI  - Electrical conductivity of aqueous salt-free concentrated suspensions. Effects of
      water dissociation and CO2 contamination.
AB  - In this paper we explore the effects of water dissociation and CO2 contamination
      on the electrical conductivity of salt-free concentrated suspensions in static
      electric fields. The conductivity model here presented is based on a new
      description of the equilibrium double layer for particles in "realistic" salt
      free suspensions recently developed by the authors to account for the latter
      effects (Ruiz-Reina, E.; Carrique, F. J. Phys. Chem. B 2008, 112, 11960). It was
      shown that in most of the cases the neglecting of those effects would lead to a
      very poor description of common salt-free suspensions, especially, but not only,
      if the suspensions have been in contact with air. As shown in this paper, the
      presence of only water dissociation ions suffices to provoke very important
      changes in the standard salt-free predictions. A realistic aqueous salt-free
      suspension consists of an aqueous suspension without any electrolyte added during
      the preparation but including the following ionic species: (i) the "added
      counterions" stemming from the particle charging process that counterbalance
      their surface charge (with just this ionic species, the suspension can be
      considered as an ideal or pure salt-free one), (ii) the H+ and OH- ions from
      water dissociation, and (iii) the ions produced by the atmospheric CO2
      contamination. The model is based on the classical Poisson-Boltzmann theory, the
      appropriate local chemical reactions, the standard electrokinetic equations, and
      the cell model approximation to account for electro-hydrodynamic particle
      particle interactions. Thus, we have studied the electrical conductivity of such
      realistic salt-free suspensions for different particle volume fraction phi and
      surface charge density sigma, and compared it with results of pure salt-free
      conductivity predictions. The numerical results have shown that water
      dissociation ions and/or CO2 contamination has an extreme influence on the
      suspension conductivity values at low-moderate particle volume fractions. In
      these situations the role of the added counterions is screened by the other ionic
      species. Even if the suspensions have not been exposed to the atmosphere, the
      quantitative changes in conductivity at low volume fractions associated with the
      presence of water dissociation ions over the added counterions are enormous. It
      is concluded that it is necessary to take into account the water dissociation
      influence for phi lower than approximately 10(-2)-10(-3), whereas the atmospheric
      CO2 contamination is not negligible if phi<10(-1)-10(-2), depending on the
      particle charge. The present work sets the basis for further theoretical models
      concerning, particularly, the dynamic electrophoresis and dielectric response of
      such systems.

PMID- 19580305
TI  - Series of metal-nonmetal-metal sandwich compounds: out-of-plane sigma-aromaticity
      and electric properties.
AB  - A new class of metal-nonmetal-metal sandwich structures M3-CO3-M3' (M, M' = Li,
      Na, K) with all real frequencies is obtained at the second-order Moller-Plesset
      theory (MP2) method with the 6-311+G (2d) basis set. Because the sandwich
      molecule M3-CO3-M3' is composed of superatoms (M3, CO3, and M3'), it is a
      sandwich "superomolecule". The superatoms M3 and M3' are electron donors and CO3
      is the acceptor, and then there is a strong charge transfer between M3 (or M3')
      and CO3 superatom, so M3-CO3-M3' can be denoted as M3(+)CO3(2-)M3'(+). Owing to
      the CO3(2-) anion in the middle repulsing the valence electrons of two metal
      rings (M3 and M3') forming a pair of excess electrons, the compound with excess
      electrons is also a novel electride. In metal-nonmetal-metal sandwich compound
      M3(+)CO3(2-)M3'(+), superatom units M3(+) and M3'(+) exhibit unusual sigma
      aromaticity: the maximum negative nucleus-independent chemical shift (NICSmax)
      value of each aromatic ring (M3(+) and M3'(+)) does not locate at the center of
      the ring plane but locates outside the ring plane. The distance value from the
      center of the M3(+) or M3'(+) ring plane to the point with NICSmax ranges from
      0.8 to 1.9 A. This shows a notable out-of-plane sigma-aromaticity for these
      sandwich compounds. What is the reason? We find that the out-of-plane sigma
      aromaticity of M3(+) (or M3'(+)) results from the action of CO3(2-)M3'(+) (or
      M3(+)CO3(2-)). For electric property, on account of excess electrons, the
      sandwich electride M3-CO3-M3' without the central symmetry can exhibit large
      static first hyperpolarizability (beta0). For Na3-CO3-K3, the beta0 value is
      close to 56,000 au.

PMID- 19580304
TI  - Absolute hydration entropies of alkali metal ions from molecular dynamics
      simulations.
AB  - Molecular dynamics simulations in combination with the free energy perturbation
      technique are used in this work to calculate absolute ion hydration entropies.
      The hydration entropies for five alkali metal ions are estimated from van't Hoff
      plots using hydration free energies calculated at eight different temperatures.
      Considering that the ion-water potentials were parametrized only on absolute
      hydration free energies and ionic radii, the absolute hydration entropies agree
      very well with experimental data. Simulation lengths of about 3 ns at each
      temperature were required to achieve an uncertainty below 1 kcal/mol for the
      entropic contribution to the hydration free energy (-TDeltaShyd). The
      uncertainties for the calculated entropies are typically four times larger than
      for the free energies. The possibility to use approximate approaches to calculate
      hydration entropies is also investigated. The entropy of creating the uncharged
      van der Waals spheres in water correlates well with the solvent accessible
      surface area of the ions. The Born continuum model and the linear response
      approximation cannot be used to predict the entropy of charging the van der Waals
      spheres in water without introducing temperature dependent empirical parameters.

PMID- 19580306
TI  - Spin-assisted layer-by-layer assembly: variation of stratification as studied
      with neutron reflectivity.
AB  - We apply neutron reflectivity to probe the internal structure of spin-assisted
      layer-by-layer (SA-LbL) films composed of electrostatically assembled
      polyelectrolytes. We find that the level of stratification and the degree of
      layer intermixing can be controlled by varying the type and concentration of salt
      during SA-LbL assembly. We observe well-defined layer structure in SA-LbL films
      when deposited from salt-free solutions. These films feature 2-nm-thick bilayers,
      which are approximately 3-fold thicker than those in conventional LbL films
      assembled under similar conditions. The addition of a 10 mM phosphate buffer
      promotes progressive layer interdiffusion with increasing distance from the
      substrate. However, adding 0.1 M NaCl to the phosphate buffer solution restores
      the layer stratification. We also find that SA-LbL films obtained from buffer
      solutions are more stratified as compared to the highly intermixed layers seen in
      conventional LbL films from buffer. Our results yield new insights into the
      mechanism of SA-LbL assembly and the final microstructure in comparison with
      traditional LbL assemblies.

PMID- 19580307
TI  - Synthesis of fully substituted pyrazoles via regio- and chemoselective
      metalations.
AB  - The full functionalization of the pyrazole ring was achieved by successive
      regioselective metalations using TMPMgCl x LiCl and TMP(2)Mg x 2 LiCl. Trapping
      with various electrophiles led to trisubstituted pyrazoles. An application to the
      synthesis of the acaricide Tebufenpyrad is reported.

PMID- 19580308
TI  - Effect of crystal size and surface functionalization on the cytotoxicity of
      silicalite-1 nanoparticles.
AB  - In this report, we describe the synthesis and characterization of nanocrystalline
      silicalite (the purely siliceous form of the zeolite, ZSM-5) of defined crystal
      size and surface functionalization and determine the effect on the type and
      degree of cytotoxicity induced in two distinct model cell lines. The silicalite
      materials were characterized by powder X-ray diffraction, dynamic light
      scattering and zeta potential, solid state NMR, thermal gravimetric analysis, and
      nitrogen adsorption using the BET method to determine specific surface area. The
      silicalite samples were functionalized with amino, thiol, and carboxy groups and
      had crystal sizes of approximately 30, 150, and 500 nm. The cytotoxicities of the
      silicalite samples with different crystal sizes and different surface functional
      groups were investigated using human embryonic kidney 293 (HEK-293) cells and
      RAW264.7 macrophage cell lines. We used the lactic dehydrogenase release assay to
      measure damage to the cell membrane, the caspase 3/7 activity assay to measure
      key molecules involved in apoptosis, and the Annexin V-propidium iodide staining
      method to provide visual confirmation of the types of cell death induced. We have
      shown that the impact of size and surface functionalization of silicalite
      nanoparticles on cell toxicity and mechanism of cell death is cell type
      dependent. Thirty nanometer silicalite nanoparticles were nontoxic in RAW264.7
      cells relative to untreated controls but caused necrosis in HEK293 cells. Carboxy
      functionalized 500 nm silicalite nanoparticles resulted in apoptosis and necrosis
      in RAW264.7 cells and predominantly activated apoptosis in HEK293 cells.

PMID- 19580309
TI  - Infrared spectroscopy of perdeuterated protonated water clusters in the vicinity
      of the clathrate cage.
AB  - We report infrared predissociation spectra of size-selected D(+)(D(2)O)(n)
      clusters in the size range n = 18-24 for comparison to previous studies of the
      corresponding H(+)(H(2)O)(n) species (Shin, J.-W.; Hammer, N. I.; Diken, E. G.;
      Johnson, M. A.; Walters, R. S.; Jaeger, T. D.; Duncan, M. A.; Christie, R. A.;
      Jordon, K. D. Science 2004, 304, 1137). For n = 18-20, two "free" OD stretch
      bands are observed and assigned to D(2)O molecules in acceptor-acceptor-donor
      (AAD) and acceptor-donor (AD) hydrogen bonding arrangements. Only the AAD band is
      observed for the n = 21 perdeuterated species. This behavior is identical to that
      observed previously for the corresponding H(+)(H(2)O)(n) clusters. Similar to the
      all-H protonated species, the AD "free" OD stretch band is also absent for the
      perdeuterated n = 22 cluster but returns for clusters larger than n = 22. Like
      the H(+)(H(2)O)(n) systems, the perdeuterated clusters have no spectral band in
      the lower frequency range where the signature of the hydronium cation is
      predicted. These observations shed new light on the intriguing spectroscopy and
      dynamics of large protonated water clusters.

PMID- 19580310
TI  - Photosynthetic antenna-reaction center mimicry: sequential energy- and electron
      transfer in a self-assembled supramolecular triad composed of boron dipyrrin,
      zinc porphyrin and fullerene.
AB  - A self-assembled supramolecular triad, a model to mimic the photochemical events
      of photosynthetic antenna-reaction center, viz., sequential energy and electron
      transfer, has been newly constructed and studied. Boron dipyrrin, zinc porphyrin,
      and fullerene respectively constitute the energy donor, electron donor, and
      electron acceptor segments of the antenna-reaction center mimicry. For the
      construction, first, boron dipyrrin was covalently attached to a zinc porphyrin
      entity bearing a benzo-18-crown-6 host segment at the opposite end of the
      porphyrin ring. Next, an alkyl ammonium functionalized fullerene was used to self
      assemble the crown ether entity via ion-dipole interactions. The newly formed
      supramolecular triad was fully characterized by spectroscopic, computational, and
      electrochemical methods. Selective excitation of the boron dipyrrin moiety in the
      dyad resulted in energy transfer over 97% efficiency creating singlet excited
      zinc porphyrin. The rate of energy transfer from the decay measurements of time
      correlated singlet photon counting (TCSPC) and up-conversion techniques agreed
      well with that obtained by the pump-probe technique and revealed efficient
      photoinduced energy transfer in the dyad (time constant in the order of 10-60 ps
      depending upon the conformer). Upon forming the supramolecular triad by self
      assembling fullerene, the excited zinc porphyrin resulted in electron transfer to
      the coordinated fullerene yielding a charge-separated state, thus mimicking the
      antenna-reaction center functionalities of photosynthesis. Nanosecond transient
      absorption studies yielded a lifetime of the charge-separated state to be 23
      micros indicating charge stabilization in the supramolecular triad. The present
      supramolecular system represents a successful model to mimic the rather complex
      "combined antenna-reaction center" events of photosynthesis.

PMID- 19580311
TI  - Synthesis and reversible reductive coupling of cationic, dinitrogen-derived
      diazoalkane complexes.
AB  - A series of cationic diazoalkane complexes [4-RC(6)H(4)C(H)NNMo(N[t
      Bu]Ar)(3)][AlCl(4)], [1-R][AlCl(4)] (R = NMe(2), Me, H, Br, CN; Ar = 3,5
      C(6)H(3)Me(2)) has been prepared by treatment of the N(2)-derived diazenido
      complex Me(3)SiNNMo(N[t-Bu]Ar)(3) with 4-RC(6)H(4)CHO and 2 equiv of AlCl(3). The
      structures of [1-H][AlCl(4)] and [1-NMe(2)][AlCl(4)] were determined by X-ray
      crystallography. The C-N and N-N stretching modes were identified by a combined
      IR and Raman spectroscopy study, and other physical properties are discussed in
      detail. The electrochemical reduction potential for [1-R][AlCl(4)] was shown to
      be linear with the Hammett sigma parameter. This reduction process forms the C-C
      bonded dimer, mu-(4-RC(6)H(4)C(H)NN)(2)[Mo(N[t-Bu]Ar)(3)](2), that was
      characterized by X-ray crystallography for R = H. Possible mechanisms for the
      formation of this dimer are presented. Both electrochemical investigations and
      quantum chemical calculations are used to describe the odd-electron complex 4
      RC(6)H(4)C(H)NNMo(N[t-Bu]Ar)(3), 1-R, that is an intermediate in the formation of
      [1-R](2). The C-C bond in [1-R](2) is redox-noninnocent and is broken upon
      oxidation. This reaction was used to prepare [1-H][A] (A = PF(6)(-), OTf(-)), and
      possible uses of this property in charge-storage devices are discussed.

PMID- 19580312
TI  - A new series of ionic liquids based on the difluorophosphate anion.
AB  - A new series of ionic liquids based on the difluorophosphate anion (PO(2)F(2)(-))
      has been synthesized by metathesis from the corresponding chloride. Incorporation
      of the PO(2)F(2)(-) anion with an N-heterocyclic cation (1-ethyl-3
      methylimidazolium (EMIm(+)), 1-butyl-3-methylimidazolium, 1-butyl-1
      methylpyrrolidinium, or 1-butyl-1-methylpiperidinium (BMPip(+))) produces ionic
      liquids with low melting points, including some room-temperature ionic liquids.
      The vibrational frequencies of PO(2)F(2)(-) in the obtained ionic liquids were
      assigned with the aid of quantum mechanical calculations. The ionic
      conductivities of the ionic liquids are comparable to those of the corresponding
      tetrafluoroborate-based ionic liquids (e.g., 12 mS cm(-1) for 1-ethyl-3
      methylimidazolium difluorophosphate, [EMIm][PO(2)F(2)]). The stability of ionic
      liquids against hydrolysis is significantly improved by replacing the
      hexafluorophosphate anion with the difluorophosphate anion, which suppresses the
      subsequent liberation of hydrogen fluoride. According to the solvatochromic
      method, the donor ability of ionic liquids based on PO(2)F(2)(-) is stronger than
      those of ionic liquids based on BF(4)(-), PF(6)(-), and N(SO(2)CF(3))(2)(-), due
      to the large negative charge on the oxygen atoms in PO(2)F(2)(-). The
      electrochemical window of [EMIm][PO(2)F(2)] is around 4.2 V, and the diffusion
      coefficients of ferrocene in [EMIm][PO(2)F(2)] are 2.83 x 10(-7) cm(2) s(-1) by
      cyclic voltammetry and 3.03 x 10(-7) cm(2) s(-1) by chronoamperometry, both of
      which are comparable to those in 1-ethyl-3-methylimidazolium tetrafluoroborate
      ([EMIm][BF(4)]). The X-ray structure of [BMPip][PO(2)F(2)] contains two cations
      and two anions in the asymmetric unit, where one of the two cations is disordered
      into two positions (chair configurations) even at -173 degrees C. The oxygen
      atoms in PO(2)F(2)(-) have closer contacts to the hydrogen atoms in BMPip(+) than
      the fluorine atoms, indicative of their stronger basicity.

PMID- 19580313
TI  - Molecular bulk heterojunctions: an emerging approach to organic solar cells.
AB  - The predicted exhaustion of fossil energy resources and the pressure of
      environmental constraints are stimulating an intensification of research on
      renewable energy sources, in particular, on the photovoltaic conversion of solar
      energy. In this context, organic solar cells are attracting increasing interest
      that is motivated by the possibility of fabricating large-area, lightweight, and
      flexible devices using simple techniques with low environmental impact. Organic
      solar cells are based on a heterojunction resulting from the contact of a donor
      (D) and an acceptor (A) material. Absorption of solar photons creates excitons,
      Coulombically bound electron-hole pairs, which diffuse to the D/A interface,
      where they are dissociated into free holes and electrons by the electric field.
      D/A heterojunctions can be created with two types of architectures, namely,
      bilayer heterojunction and bulk heterojunction (BHJ) solar cells. BHJ cells
      combine the advantages of easier fabrication and higher conversion efficiency due
      to the considerably extended D/A interface. Until now, the development of BHJ
      solar cells has been essentially based on the use of soluble pi-conjugated
      polymers as donor material. Intensive interdisciplinary research carried out in
      the past 10 years has led to an increase in the conversion efficiency of BHJ
      cells from 0.10 to more than 5.0%. These investigations have progressively
      established regioregular poly(3-hexylthiophene) (P3HT) as the standard donor
      material for BHJ solar cells, owing to a useful combination of optical and charge
      transport properties. However, besides the limit imposed to the maximum
      conversion efficiency by its intrinsic electronic properties, P3HT and more
      generally polymers pose several problems related to the control of their
      structure, molecular weight, polydispersity, and purification. In this context,
      recent years have seen the emergence of an alternative approach based on the
      replacement of polydisperse polymers by soluble, conjugated single molecules as
      donor materials in BHJ cells. In fact, molecular donors present specific
      advantages in terms of structural definition, synthesis, and purification. In
      this Account, we present a brief survey of recent work in this nascent field of
      new single-molecule donors in organic solar cells. Various series of three
      dimensional donors built by the attachment of different kinds of conjugated
      branches on a central node, including silicon, twisted bithiophene,
      triphenylamine, and borondipyrromethene (BODIPY), are discussed in relation to
      the performances of the resulting solar cells. Furthermore, it is shown that the
      concept of a molecular donor with internal charge transfer leads at the same time
      to improved light-harvesting properties, red-shifted photoresponse, and a higher
      open-circuit voltage, resulting in a considerable increase of conversion
      efficiency, up to values now approaching 3%. These results show that soluble
      molecular donors can lead to BHJ cells that combine high conversion efficiency
      with the distinct advantages of working with single molecules, including
      structural definition, synthesis, purification, and reproducibility.

PMID- 19580314
TI  - Hydrogenation of the alpha,beta-unsaturated aldehydes acrolein, crotonaldehyde,
      and prenal over Pt single crystals: a kinetic and sum-frequency generation
      vibrational spectroscopy study.
AB  - Sum-frequency generation vibrational spectroscopy (SFG-VS) and kinetic
      measurements using gas chromatography have been used to study the surface
      reaction intermediates during the hydrogenation of three alpha,beta-unsaturated
      aldehydes, acrolein, crotonaldehyde, and prenal, over Pt(111) at Torr pressures
      (1 Torr of aldehyde, 100 Torr of hydrogen) in the temperature range of 295-415 K.
      SFG-VS data showed that acrolein has mixed adsorption species of eta(2)-di
      sigma(CC)-trans, eta(2)-di-sigma(CC)-cis as well as highly coordinated eta(3) or
      eta(4) species. Crotonaldehyde adsorbed to Pt(111) as eta(2) surface
      intermediates. SFG-VS during prenal hydrogenation also suggested the presence of
      the eta(2) adsorption species and became more highly coordinated as the
      temperature was raised to 415 K, in agreement with its enhanced C=O
      hydrogenation. The effect of catalyst surface structure was clarified by carrying
      out the hydrogenation of crotonaldehyde over both Pt(111) and Pt(100) single
      crystals while acquiring the SFG-VS spectra in situ. Both the kinetics and SFG-VS
      showed little structure sensitivity. Pt(100) generated more decarbonylation
      "cracking" product while Pt(111) had a higher selectivity for the formation of
      the desired unsaturated alcohol, crotyl alcohol.

PMID- 19580315
TI  - Electrochemical isotope effect and lithium isotope separation.
AB  - A large electrochemical isotopic effect is observed upon the electrodeposition of
      lithium from solutions of propylene carbonate producing isotopically light metal
      deposits. The magnitude of fractionation is controlled by the applied
      overpotential and is largest close to equilibrium. Calculated partition function
      ratios for tetrahedrally coordinated lithium complexes and metallic lithium
      predict an equilibrium fractionation close to that measured experimentally.

PMID- 19580316
TI  - Memory of chirality of tertiary aromatic amides: a simple and efficient method
      for the enantioselective synthesis of quaternary alpha-amino acids.
AB  - A new methodology for the asymmetric synthesis of quaternary alpha-substituted
      amino acids using memory of chirality has been developed. The strategy utilizes
      the dynamic axial chirality of tertiary aromatic amides to memorize the initial
      chirality of an alpha-amino acid during an enolization step. Starting from five
      different l-amino acids, the corresponding oxazolidin-5-ones containing a
      tertiary aromatic amide group have been synthesized in one step and then
      alkylated with various electrophiles, with good yields and enantioselectivities
      (up to 96% and up to >99% after recrystallization). One-step deprotection affords
      enantioenriched or enantiopure quaternary alpha-amino acids. We describe here the
      optimization process, the results obtained in each series and a plausible
      explanation, based on NMR studies, DFT calculations and crystallographic
      structures. The methodology presented herein constitutes an efficient synthesis
      of enantiopure quaternary alpha-amino acids (three steps only) starting from
      tertiary l-amino acids, without any external source of chirality.

PMID- 19580317
TI  - Green electrogenerated chemiluminescence of highly fluorescent benzothiadiazole
      and fluorene derivatives.
AB  - A group of highly fluorescent 2,1,3-benzothiadiazole derivatives (BH0-BH3),
      including two fluorene derivatives (AB2 and C01) were synthesized and
      characterized. The electrochemical, spectroscopic, and electrogenerated
      chemiluminescence (ECL) properties of the compounds were determined.
      Benzothiadiazole derivatives BH1, BH2, and BH3 show reversible oxidation and
      reduction waves and produce strong green ECL in nonaqueous solutions. This ECL
      could be seen by the naked eye, even in a well lit room. The fluorene
      derivatives, C01 and AB2, also produce bright, easily observable ECL. Since the
      ECL spectra are at essentially the same wavelengths as the photoluminescence (PL)
      spectra, and the energies of the electron transfer reactions are greater than the
      singlet state energies, we propose direct formation of the excited singlet state
      during ion annihilation. BH0, which shows a quasi-reversible oxidation wave, only
      produced weak ECL via direct annihilation but gave strong ECL with benzoyl
      peroxide (BPO) as a coreactant. The ECL quantum efficiencies of the series,
      compared to that of 9,10-diphenylanthrace, was estimated to range from 0.05 to
      7%. This series shows rare green photoluminescence (lambda(PL) = 490-556 nm) with
      a high PL quantum efficiency in solution (Phi = 5 to 90%).

PMID- 19580319
TI  - Aromatic 2-(thio)ureidocarboxylic acids as a new family of modulators of
      multidrug resistance-associated protein 1: synthesis, biological evaluation, and
      structure-activity relationships.
AB  - Four series of aromatic carboxylic acids were prepared with a urea or thiourea
      moiety at the neighboring position to the carboxyl group and benzene or thiophene
      as aromatic scaffold. Using a calcein AM assay, these compounds were evaluated as
      inhibitors of multidrug resistance-associated protein 1 (MRP1) and selected
      compounds were examined toward P-glycoprotein (P-gp) as well as breast cancer
      resistance protein (BCRP) to assess selectivity for MRP1. Two 2
      thioureidobenzo[b]thiophene-3-carboxylic acids (48, 49) were identified as
      particularly potent inhibitors of MRP1, with IC50 values of around 1 microM. The
      structural features of this new family of nontoxic MRP1 inhibitors include a
      (thio)urea disubstituted with preferentially two alkyl groups at the terminal
      nitrogen and an additional fused aromatic ring.

PMID- 19580318
TI  - Endo-selective enyne ring-closing metathesis promoted by stereogenic-at-Mo
      monoalkoxide and monoaryloxide complexes. Efficient synthesis of cyclic dienes
      not accessible through reactions with Ru carbenes.
AB  - Stereogenic-at-Mo monoalkoxide and monoaryloxide complexes promote enyne ring
      closing metathesis (RCM) reactions, affording the corresponding endo products
      with high selectivity (typically >98:<2 endo:exo). All catalysts can be prepared
      and used in situ. Five-, six-, and seven-membered rings are obtained through
      reactions with enyne substrates that bear all-carbon tethers as well as those
      that contain heteroatom substituents. The newly developed catalytic protocols
      complement the related exo-selective Ru-catalyzed processes. In cases where Ru
      based complexes deliver exo and endo products nondiscriminately, such as when
      tetrasubstituted cyclic alkenes are generated, Mo-catalyzed reactions afford the
      endo product exclusively. The efficiency of synthesis of N- and O-containing endo
      diene heterocycles can be improved significantly through structural modification
      of Mo catalysts. The modularity of Mo-based monopyrrolides is thus exploited in
      the identification of the most effective catalyst variants. Through alteration of
      O-based monodentate ligands, catalysts have been identified that promote enyne
      RCM with improved efficiency. The structural attributes of three Mo complexes are
      elucidated through X-ray crystallography. The first examples of catalytic
      enantioselective enyne RCM reactions are reported (up to 98:2 enantiomer ratio
      and >98% endo).

PMID- 19580320
TI  - Focus on the controversial activation of human iNKT cells by 4-deoxy analogue of
      KRN7000.
AB  - 4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for
      the stimulation of human iNKT cells, but this remains strongly debated. In this
      work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a
      metathesis reaction allowing sphingosine modifications from a single ethylenic
      alpha-galactoside precursor. The 4-deoxy-KRN7000 derivative 2, described here,
      induced potent cytokinic responses, comparable to those of KRN7000, both from
      human iNKT cells in vitro and from their murine counterpart in vivo.

PMID- 19580321
TI  - Solid-state and solution NMR studies of the CAP-Gly domain of mammalian dynactin
      and its interaction with microtubules.
AB  - Microtubules (MTs) and microtubule binding proteins (MTBPs) play fundamental
      physiological roles including vesicle and organelle transport, cell motility, and
      cell division. Despite the importance of the MT/MTBP assemblies, there remains
      virtually no structural or dynamic information about their interaction at the
      atomic level due to the inherent insolubility and lack of long-range order of
      MTs. In this study, we present a combined magic angle spinning solid-state and
      solution NMR study of the MTBP CAP-Gly domain of mammalian dynactin and its
      interaction with paclitaxel-stabilized microtubules. We report resonance
      assignments and secondary structure analysis of the free CAP-Gly in solution and
      in the solid state by a combination of two- and three-dimensional homo- and
      heteronuclear correlation spectra. In solution, binding of CAP-Gly to
      microtubules is accompanied by the broadening of the majority of the peaks in
      HSQC spectra except for the residues at the termini, precluding further
      structural analysis of the CAP-Gly/microtubule complexes. In the solid state,
      DARR spectra of free CAP-Gly and its complex with microtubules display well
      resolved lines, permitting residue-specific resonance assignments. Interestingly,
      a number of chemical shifts in the solid-state DARR spectra of the CAP
      Gly/microtubule complex are perturbed compared to those of the free CAP-Gly,
      suggesting that conformational changes occur in the protein upon binding to the
      microtubules. These results indicate that CAP-Gly/microtubule assemblies are
      amenable to detailed structural characterization by magic angle spinning NMR
      spectroscopy and that solid-state NMR is a viable technique to study MT/protein
      interactions in general.

PMID- 19580322
TI  - Mechanism of helix induction in poly(4-carboxyphenyl isocyanide) with chiral
      amines and memory of the macromolecular helicity and its helical structures.
AB  - An optically inactive poly(4-carboxyphenyl isocyanide) (poly-1-H) changed its
      structure into the prevailing, one-handed helical structure upon complexation
      with optically active amines in dimethylsulfoxide (DMSO) and water, and the
      complexes show a characteristic induced circular dichroism in the polymer
      backbone region. Moreover, the macromolecular helicity induced in water and
      aqueous organic solutions containing more than 50 vol % water could be
      "memorized" even after complete removal of the chiral amines (h-poly-1b-H), while
      that induced in DMSO and DMSO-water mixtures containing less than 30 vol % water
      could not maintain the optical activity after removal of the chiral amines (poly
      1a-H). We now report fully detailed studies of the helix induction mechanism with
      chiral amines and the memory of the macromolecular helicity in water and a DMSO
      water mixture by various spectroscopic measurements, theoretical calculations,
      and persistence length measurements together with X-ray diffraction (XRD)
      measurements. From the spectroscopic results, such as circular dichroism (CD),
      absorption, IR, vibrational CD, and NMR of poly-1a-H, h-poly-1b-H, and original
      poly-1-H, we concluded that the specific configurational isomerization around the
      C horizontal lineN double bonds occurs during the helicity induction process in
      each solvent. In order to obtain the structural information, XRD measurements
      were done on the uniaxially oriented films of the corresponding methyl esters
      (poly-1-Me, poly-1a-Me, and h-poly-1b-Me) prepared from their liquid crystalline
      polymer solutions. On the basis of the XRD analyses, the most plausible helical
      structure of poly-1a-Me was proposed to be a 9-unit/5-turn helix with two monomer
      units as a repeating unit, and that of h-poly-1b-Me was proposed to be a 10
      unit/3-turn helix consisting of one repeating monomer unit. The density
      functional theory calculations of poly(phenyl isocyanide), a model polymer of h
      poly-1b-Me, afforded a 7-unit/2-turn helix as the most possible helical
      structure, which is in good agreement with the XRD results. Furthermore, the
      persistence length measurements revealed that these structural changes accompany
      a significant change in the main-chain stiffness. The mechanism of helix
      induction in poly-1-H and the memory of the macromolecular helicity are discussed
      on the basis of these results.

PMID- 19580323
TI  - Proteome maps of the main human peripheral blood constituents.
AB  - Clinical proteome analysis will almost inevitably be confronted with blood
      constituents. Purified plasma, serum, cell or tissue samples may easily be
      contaminated with some other constituents, affecting the final proteome analysis
      result. To recognize proteins which are potentially indicative for the presence
      of major blood constituents, we purified T cells, monocytes, neutrophils,
      erythrocytes, platelets and plasma and performed comparative proteome profiling
      employing 2D-PAGE in addition to shotgun proteomics. By mass analysis, 594
      different proteins were identified in the 2D gels. Six of the 594 proteins
      displayed a highly specific expression pattern. A total of 1774 proteins were
      identified by shotgun proteomics, including 50 proteins with highly specific
      expression patterns. Indeed, proteins specific for each of the constituents were
      successfully identified. All protein lists including mass spectrometry details
      and expression specificity are freely available via the PRIDE database and the
      CPL/MUW database. The present protein maps of each of the constituents may serve
      as references for comparative analyses and will aid the interpretation of
      proteome profiles of clinical samples.

PMID- 19580324
TI  - Biochemical analysis of PKR activation by PACT.
AB  - Many extracellular stresses cause inhibition of translation initiation by
      triggering phosphorylation of the initiation factor, eIF-2alpha. A major protein
      kinase responsible for this phosphorylation is PKR, a latent kinase which itself
      needs to be activated by autophosphorylation. In stressed cells, this activation
      occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR. We
      have previously demonstrated that the presence of specific residues in domain 3
      of PACT is necessary for its ability to activate PKR in vivo. Here, we analyze
      the biochemical properties of the inactive PACT mutants by assessing their
      ability to bind and activate PKR in vitro. Among the essential residues, two
      serines need to be phosphorylated in vivo for PACT's ability to activate PKR. We
      substituted those serines with aspartic acids, mimics of phosphoserines, and
      investigated the properties of the corresponding mutant PACTs. In vitro, they
      activate PKR more efficiently because they bind to PKR more tightly. These
      results indicate that stress-induced phosphorylation of specific serine residues
      in domain 3 of PACT increases its affinity for PKR, which leads to better
      activation of PKR and resultant eIF-2alpha phosphorylation.

PMID- 19580326
TI  - The recognition pathway for the DNA cytosine methyltransferase M.HhaI.
AB  - Enzymatic sequence-specific DNA modification involves multiple poorly understood
      intermediates. DNA methyltransferases like M.HhaI initially bind nonspecific DNA
      and then selectively bind and modify a unique sequence. High-resolution NMR was
      used to map conformational changes occurring in M.HhaI upon binding nonspecific
      DNA, a one base pair altered noncognate DNA sequence, and both hemimethylated and
      unmethylated cognate DNA sequences. Comparisons with previous NMR studies of the
      apoenzyme and enzyme-cofactor complex provide snapshots of the pathway to
      sequence-specific complex formation. Dramatic chemical shift perturbations
      reaching many distal sites within the protein are detected with cognate DNA,
      while much smaller changes are observed upon nonspecific and noncognate DNA
      binding. A cooperative rather than stepwise transition from a nonspecific to a
      cognate complex is revealed. Furthermore, switching from unmethylated to
      hemimethylated cognate DNA involves detectable protein conformational changes 20
      30 A away from the methyl group, indicating high protein sensitivity and
      plasticity to DNA modification.

PMID- 19580325
TI  - Ambivalent incorporation of the fluorescent cytosine analogues tC and tCo by
      human DNA polymerase alpha and Klenow fragment.
AB  - We studied the incorporation of the fluorescent cytidine analogues 1,3-diaza-2
      oxophenothiazine (tC) and 1,3-diaza-2-oxophenoxazine (tCo) by human DNA
      polymerase alpha and Klenow fragment of DNA polymerase I (Escherichia coli).
      These tricyclic nucleobases possess the regular hydrogen bonding interface of
      cytosine but are significantly expanded in size toward the major groove. Despite
      the size alteration, both DNA polymerases insert dtCTP and dtCoTP with remarkable
      catalytic efficiency. Polymerization opposite guanine is comparable to the
      insertion of dCTP, while the insertion opposite adenine is only approximately 4
      11 times less efficient than the formation of a T-A base pair. Both enzymes
      readily extend the formed tC(o)-G and tC(o)-A base pairs and can incorporate at
      least four consecutive nucleotide analogues. Consistent with these results, both
      DNA polymerases efficiently polymerize dGTP and dATP when tC and tCo are in the
      template strand. Klenow fragment inserts dGTP with a 4-9-fold higher probability
      than dATP, while polymerase alpha favors dGTP over dATP by a factor of 30-65.
      Overall, the properties of tC(o) as a templating base and as an incoming
      nucleotide are surprisingly symmetrical and may be universal for A and B family
      DNA polymerases. This finding suggests that the aptitude for ambivalent base
      pairing is a consequence of the electronic properties of tC(o).

PMID- 19580327
TI  - Molecular mechanism for the denaturation of proteins by urea.
AB  - Understanding protein-solute interactions is one of the sizable challenges of
      protein chemistry; therefore, numerous experimental studies have attempted to
      explain the mechanism by which proteins unfold in aqueous urea solutions. On the
      basis of kinetic evidence at low urea concentrations, (1)H NMR spectroscopic
      analysis, and molecular orbital calculations, we propose a mechanistic model for
      the denaturation of RNase A in urea. Our results support a direct interaction
      between urea and protonated histidine as the initial step for protein
      inactivation followed by hydrogen bond formation with polar residues, and the
      breaking of hydrophobic collapse as the final steps for protein denaturation.
      With the proposed model, we can rationalize apparently conflicting results in the
      literature about the mechanism of protein denaturation with urea.

PMID- 19580328
TI  - Identification of aminothienopyridazine inhibitors of tau assembly by
      quantitative high-throughput screening.
AB  - Inclusions comprised of fibrils of the microtubule- (MT-) associated protein tau
      are found in the brains of those with Alzheimer's disease (AD) and other
      neurodegenerative tauopathies. The pathology that is observed in these diseases
      is believed to result from the formation of toxic tau oligomers or fibrils and/or
      from the loss of normal tau function due to its sequestration into insoluble
      deposits. Hence, small molecules that prevent tau oligomerization and/or
      fibrillization might have therapeutic value. Indeed, examples of such compounds
      have been published, but nearly all have properties that render them unsuitable
      as drug candidates. For these reasons, we conducted quantitative high-throughput
      screening (qHTS) of approximately 292000 compounds to identify drug-like
      inhibitors of tau assembly. The fibrillization of a truncated tau fragment that
      contains four MT-binding domains was monitored in an assay that employed
      complementary thioflavin T fluorescence and fluorescence polarization methods.
      Previously described classes of inhibitors as well as new scaffolds were
      identified, including novel aminothienopyridazines (ATPZs). A number of ATPZ
      analogues were synthesized, and structure-activity relationships were defined.
      Further characterization of representative ATPZ compounds showed they do not
      interfere with tau-mediated MT assembly, and they are significantly more
      effective at preventing the fibrillization of tau than the Abeta(1-42) peptide
      which forms AD senile plaques. Thus, the ATPZ molecules described here represent
      a novel class of tau assembly inhibitors that merit further development for
      testing in animal models of AD-like tau pathology.

PMID- 19580329
TI  - RapA, the SWI/SNF subunit of Escherichia coli RNA polymerase, promotes the
      release of nascent RNA from transcription complexes.
AB  - RapA, a prokaryotic member of the SWI/SNF protein superfamily, is an integral
      part of the RNA polymerase transcription complex. RapA's function and catalytic
      mechanism have been linked to nucleic acid remodeling. In this work, we show that
      mutations in the interface between RapA's SWI/SNF and double-stranded nucleic
      acid-binding domains significantly alter ATP hydrolysis in purified RapA. The
      effects of individual mutations on ATP hydrolysis loosely correlated with RapA's
      nucleic acid remodeling activity, indicating that the interaction between these
      domains may be important for the RapA-mediated remodeling of nonproductive
      transcription complexes. In this study, we introduced a model system for in vitro
      transcription of a full-length Escherichia coli gene (slyD). To study the
      function of RapA, we fractionated and identified in vitro transcription reaction
      intermediates in the presence or absence of RapA. These experiments demonstrated
      that RapA contributes to the formation of free RNA species during in vitro
      transcription. This work further refines our models for RapA function in vivo and
      establishes a new role in RNA management for a representative of the SWI/SNF
      protein superfamily.

PMID- 19580330
TI  - Impact of actin glutathionylation on the actomyosin-S1 ATPase.
AB  - Glutathionylation of intracellular proteins is an established physiological
      regulator of protein function. In multiple models, including ischemia-reperfusion
      of the heart, increased oxidative stress results in the glutathionylation of
      sarcomeric actin. We hypothesized that actin glutathionylation may play a role in
      the multifactorial change in cardiac muscle contractility observed during this
      pathophysiological state. Therefore, the functional impact of glutathionylated
      actin on the interaction with myosin-S1 was examined. Substituting
      glutathionylated F-actin for unmodified F-actin reduced the maximum actomyosin-S1
      ATPase, and this was accompanied by an increase in the activation energy of the
      steady state ATPase. Measurement of steady state binding did not suggest a large
      impact of actin glutathionylation on the binding to myosin-S1. However, transient
      binding and dissociation kinetics determined by stopped-flow methods demonstrated
      that although actin glutathionylation did not significantly alter the rate
      constant of myosin-S1 binding, there was a significant decrease in the rate of
      ATP-induced myosin-S1 detachment in the presence of ADP. These results suggest
      that actin glutathionylation may play a limited but defined role in the
      alteration of contractility following oxidative stress to the myocardium,
      particularly through a decrease in the actomyosin ATPase activity.

PMID- 19580332
TI  - Escherichia coli DNA adenine methyltransferase: intrasite processivity and
      substrate-induced dimerization and activation.
AB  - Methylation of GATC sites in Escherichia coli by DNA adenine methyltransferase
      (EcoDam) is essential for proper DNA replication timing, gene regulation, and
      mismatch repair. The low cellular concentration of EcoDam and the high number of
      GATC sites in the genome (approximately 20000) support the reliance on
      methylation efficiency-enhancing strategies such as extensive intersite
      processivity. Here, we present evidence that EcoDam has evolved other unique
      mechanisms of activation not commonly observed with restriction-modification
      methyltransferases. EcoDam dimerizes on short, synthetic DNA, resulting in
      enhanced catalysis; however, dimerization is not observed on large genomic DNA
      where the potential for intersite processive methylation precludes any
      dimerization-dependent activation. An activated form of the enzyme is apparent on
      large genomic DNA and can also be achieved with high concentrations of short,
      synthetic substrates. We suggest that this activation is inherent on polymeric
      DNA where either multiple GATC sites are available for methylation or the
      partitioning of the enzyme onto nonspecific DNA is favored. Unlike other
      restriction-modification methyltransferases, EcoDam carries out intrasite
      processive catalysis whereby the enzyme-DNA complex methylates both strands of an
      unmethylated GATC site prior to dissociation from the DNA. This occurs with short
      21 bp oligonucleotides and is highly dependent upon salt concentrations. Kinetic
      modeling which invokes enzyme activation by both dimerization and excess
      substrate provides mechanistic insights into key regulatory checkpoints for an
      enzyme involved in multiple, diverse biological pathways.

PMID- 19580331
TI  - A rare nucleotide base tautomer in the structure of an asymmetric DNA junction.
AB  - The single-crystal structure of a DNA Holliday junction assembled from four
      unique sequences shows a structure that conforms to the general features of
      models derived from similar constructs in solution. The structure is a compact
      stacked-X form junction with two sets of stacked B-DNA-type arms that coaxially
      stack to form semicontinuous duplexes interrupted only by the crossing of the
      junction. These semicontinuous helices are related by a right-handed rotation
      angle of 56.5 degrees, which is nearly identical to the 60 degree angle in the
      solution model but differs from the more shallow value of approximately 40
      degrees for previous crystal structures of symmetric junctions that self-assemble
      from single identical inverted-repeat sequences. This supports the model in which
      the unique set of intramolecular interactions at the trinucleotide core of the
      crossing strands, which are not present in the current asymmetric junction,
      affects both the stability and geometry of the symmetric junctions. An unexpected
      result, however, is that a highly wobbled A.T base pair, which is ascribed here
      to a rare enol tautomer form of the thymine, was observed at the end of a
      CCCC/GGGG sequence within the stacked B-DNA arms of this 1.9 A resolution
      structure. We suggest that the junction itself is not responsible for this
      unusual conformation but served as a vehicle for the study of this CG-rich
      sequence as a B-DNA duplex, mimicking the form that would be present in a
      replication complex. The existence of this unusual base lends credence to and
      defines a sequence context for the "rare tautomer hypothesis" as a mechanism for
      inducing transition mutations during DNA replication.

PMID- 19580333
TI  - Hydrolytic properties and substrate specificity of the foot-and-mouth disease
      leader protease.
AB  - Foot-and-mouth disease virus, a global animal pathogen, possesses a single
      stranded RNA genome that, on release into the infected cell, is immediately
      translated into a single polyprotein. This polyprotein product is cleaved during
      synthesis by proteinases contained within it into the mature viral proteins. The
      first cleavage is performed by the leader protease (Lb(pro)) between its own C
      terminus and the N-terminus of VP4. Lb(pro) also specifically cleaves the two
      homologues of cellular eukaryotic initiation factor (eIF) 4G, preventing
      translation of capped mRNA. Viral protein synthesis is initiated internally and
      is thus unaffected. We used a panel of specifically designed FRET peptides to
      examine the effects of pH and ionic strength on Lb(pro) activity and investigate
      the size of the substrate binding site and substrate specificity. Compared to the
      class prototypes, papain and the cathepsins, Lb(pro) possesses several unusual
      characteristics, including a high sensitivity to salt and a very specific
      substrate binding site extending up to P(7). Indeed, almost all substitutions
      investigated were detrimental to Lb(pro) activity. Analysis of structural data
      showed that Lb(pro) binds residues P(1)-P(3) in an extended conformation, whereas
      residues P(4)-P(7) are bound in a short 3(10) helix. The specificity of Lb(pro)
      as revealed by the substituted peptides could be explained for all positions
      except P(5). Strikingly, Lb(pro) residues L178 and L143 contribute to the
      architecture of more than one substrate binding pocket. The diverse functions of
      these two Lb(pro) residues explain why Lb(pro) is one of the smallest, but
      simultaneously most specific, papain-like enzymes.

PMID- 19580334
TI  - Structure-dependent charge density as a determinant of antimicrobial activity of
      peptide analogues of defensin.
AB  - Defensins are small (3-5 kDa) cysteine-rich cationic proteins found in both
      vertebrates and invertebrates constituting the front line of host innate
      immunity. Despite intensive research, bactericidal and cytotoxic mechanisms of
      defensins are still largely unknown. Moreover, we recently demonstrated that
      small peptides derived from defensins are even more potent bactericidal agents
      with less toxicity toward host cells. In this paper, structures of three C
      terminal (R36-K45) analogues of human beta-defensin-3 were studied by 1H NMR
      spectroscopy and extensive molecular dynamics simulations. Because of indications
      that these peptides might target the inner bacterial membrane, they were
      reconstituted in dodecylphosphocholine or dodecylphosphocholine/1-palmitoyl-2
      oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] mixed micelles, and lipid bicelles
      mimicking the phospholipid-constituted bilayer membrane of mammalian and
      bacterial cells. The results show that the binding affinity and partitioning into
      the lipid phase and the ability to dimerize and accrete well-defined structures
      upon interactions with lipid membranes contribute to compactization of positive
      charges within peptide oligomers. The peptide charge density, mediated by
      corresponding three-dimensional structures, was found to directly correlate with
      the antimicrobial activity. These novel observations may provide a new rationale
      for the design of improved antimicrobial agents.

PMID- 19580335
TI  - Effects of diesel and interactions with copper and other metals in an estuarine
      sediment microbial community.
AB  - Estuarine sediment microcosms were treated with combinations of diesel, copper
      (at two levels), and a mixture of heavy metals (mercury, cadmium, lead, and
      chromium; at two levels) mimicking the contaminant loadings found in harbor
      sediments. The effects on the microbial community were monitored by polar lipid
      fatty acid analysis. Diesel addition increased microbial biomass, caused shifts
      in some fatty acid structural groups, and decreased starvation biomarkers.
      Incorporation of diesel hydrocarbons into lipids was expressed as an increase in
      the proportion of odd-carbon-number fatty acids. No treatment with the metals
      mixture (mercury, cadmium, lead, and chromium) alone significantly changed any
      parameter derived from the polar lipid fatty acids, but the increase in microbial
      biomass from diesel addition was higher with the metals mixture, possibly because
      of indirect effects caused by reductions in grazing resulting from metal-induced
      toxicity to bacteriovorous nematodes. Copper also modified the effects of diesel
      addition, preventing biomass increase but not diesel degradation, suggesting that
      some of the energy gained from diesel oxidation was expended combating copper
      toxicity. In the present study, observations indicate that metals in general, and
      copper in particular, can modify the response of sedimentary microorganisms to
      petroleum-hydrocarbon contaminants.

PMID- 19580336
TI  - Factors affecting the degradation of pharmaceuticals in agricultural soils.
AB  - Pharmaceuticals may be released to the soil environment through the application
      of biosolids to land. To understand those factors affecting the persistence of
      pharmaceuticals in the soil environment, the present study was performed to
      assess the effects of soil type, the presence of biosolids, and the impact of
      chemical mixture interactions on the degradation of three pharmaceuticals:
      naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that
      naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d
      and in biosolids with a half-life of 10.2 d. No relationships were observed
      between degradation rate and soil physicochemical properties and soil
      bioactivity. For naproxen, addition of biosolids to soils reduced the degradation
      rate observed in the soil-only studies, with half-lives in the soil-biosolid
      systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be
      persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was
      assessed using a mixture of the three study compounds and the sulfonamide
      antibiotic sulfamethazine, the degradation behavior of fluoxetine and
      carbamazepine was similar to that observed in the single compound studies (i.e.,
      no degradation). However, the degradation rate of naproxen in soils, biosolids,
      and soil-biosolid systems spiked with the mixture was significantly slower than
      in the single-compound studies. As degradation studies for risk assessment
      purposes are performed using single substances in soil-only studies, it is
      possible that current risk assessment procedures will underestimate environmental
      impacts. Further work is therefore warranted on a larger range of substances,
      soils, biosolid types, and chemical mixtures to better understand the fate of
      pharmaceuticals in terrestrial systems.

PMID- 19580337
TI  - A side population of cells from a human pancreatic carcinoma cell line harbors
      cancer stem cell characteristics.
AB  - We used flow cytometry and a DNA-binding dye efflux assay to isolate a side
      population (SP) of cells with stem cell characteristics from the human pancreatic
      carcinoma cell line, PANC-1. Non-obese diabetic/severe combined immunodeficiency
      mouse xenograft experiments showed that SP cells were enriched in tumor
      initiating capability compared with non-SP cells. Cultured SP cells were able to
      differentiate into daughter cells and non-SP cells, through asymmetric division.
      Our study demonstrated that SP cells had high drug-resistance, both in vivo and
      in vitro. SP cells also showed significantly higher levels of mRNA expression for
      CD133, ABCG2 and Notch1, when compared to non-SP cells. Furthermore, xenografted
      tumors derived from injected SP cells and treated with gemcitabine had more
      CD133+ cells than untreated ones. We therefore suggest that these SP cells from
      the PANC-1 cell line were enriched with cancer stem cells.

PMID- 19580338
TI  - Reduced inducibility of SOCS3 by interferon gamma associates with higher
      resistance of human breast cancer lines as compared to normal mammary epithelial
      cells.
AB  - The resistance to interferons (IFNs) limits their anticancer therapeutic
      efficacy. Here we studied the antiproliferative effect of interferon gamma in
      relation to SOCS3 expression in a panel of breast cancer cell lines and normal
      mammary epithelial cells. Compared to normal cells most breast cancer lines (7/8)
      were highly resistant to IFN-gamma. Using Northern blot and real time RT-PCR we
      investigated transcription of SOCS3 genes. All normal epithelial cells (4/4)
      showed SOCS3 induction (2-14 fold) while most breast cancer lines did not or
      weakly activated SOCS3 after the interferon gamma treatment. Among the cancer
      lines, the MDA-MB-468 cells showed increased sensitivity to IFN-gamma and
      relatively high level of SOCS3 induction (2-3 fold). Together, there was a good
      correlation

PMID- 19580339
TI  - Brazilein inhibits survivin protein and mRNA expression and induces apoptosis in
      hepatocellular carcinoma HepG2 cells.
AB  - Hepatocellular carcinomas represent the third leading cause of cancer-related
      deaths worldwide. Survivin, a structurally unique member of the inhibitor of
      apoptosis protein (IAP) family, is overexpressed in a wide range of malignancies,
      including hepatocellular carcinoma. Due to its involvement in cancer progression
      and treatment resistance, survivin is currently undergoing extensive
      investigation as a novel intervention target to induce apoptosis in cancer cells
      by phytochemicals or synthetic agents. Brazilein, a compound obtained in a large
      amount from the dried heartwood of Caesalpinia sappan Linn., which has long been
      used in traditional medicine in China, has some pharmacological activities. Human
      hepatocellular carcinoma HepG2 cells were treated with brazilein and analyzed for
      survivin protein and mRNA levels by Western blotting and real-time RT-PCR,
      respectively. Brazilein treatment of cells for 48 h at 5 and 10 microg/ml doses
      resulted in significantly decrease in survivin protein expression. We also
      observed that brazilein caused a strong decrease in survivin mRNA expression. In
      other studies, down-regulation of survivin by brazilein was associated with a
      strong and prominent caspases-9 and -3 activation as well as PARP cleavage. It
      was also shown that brazilein induced a strong apoptotic cell death, as shown by
      DNA ladder assay, and growth inhibition of HepG2 cells. Further studies are
      needed to investigate in vivo effect of brazilein on survivin expression and
      associated biological effects in hepatocellular carcinoma that could provide
      useful information for brazilein efficacy in the prevention/intervention of human
      hepatocellular carcinoma.

PMID- 19580340
TI  - WT1 expression in peripheral leukocytes of patients with chronic myeloid leukemia
      serves for the prediction of Imatinib resistance.
AB  - The determination of patient's resistance to a particular drug contributes to
      more efficient therapeutical approach. The aim of this study was to evaluate if
      the responsiveness of Chronic Myeloid Leukemia (CML) patients to Imatinib therapy
      was predictable from WT1 gene expression in peripheral blood leukocytes. To
      examine the resistance we implemented an in vitro cultivation of the primary
      cells of 48 CML patients with Imatinib. The effect of Imatinib was characterized
      not only by the expression of WT1 but also by BCR-ABL, and proliferative factor
      Ki-67. <br />Our results showed that leukocytes of CML patients, clinically
      responsive to Imatinib treatment, significantly decreased WT1 expression after in
      vitro incubation with Imatinib. It was accompanied by an inhibition of expression
      of Ki-67 but not BCR-ABL. In leukocytes of CML patients clinically resistant to
      Imatinib, the expression of WT1, Ki-67, and BCR-ABL remained unaffected. The
      presented results showed that in vitro testing using peripheral blood cells
      enabled clinicians to predict responsiveness of CML patients to Imatinib.

PMID- 19580341
TI  - Kinetics of tumor marker decline as an independent prognostic factor in patients
      with relapsed metastatic germ-cell tumors.
AB  - Early serum tumor marker decline (STMD) during chemotherapy was shown to predict
      survival in patients with poor prognosis non-seminomatous germ cell tumors (GCT)
      in the first line. The aim of the study was to assess the prognostic value of
      STMD in relapsed GCT;s patients. From January 1995 to December 2007, all patients
      treated for GCT s with salvage therapy at the National Cancer Institute of
      Slovakia were identified from the tumor registry database and screened
      retrospectively for serum AFP and betaHCG level at the time of relapse. STMD rate
      was calculated for each patient and each tumor marker with an abnormal marker
      value at baseline and each tumor marker M (HCG or AFP) using only two values: the
      baseline value (M0) and the value obtained after one cycle of chemotherapy (day
      21 value; M1). The decline rate was calculated using a logarithmic
      transformation, and it was expressed as a theoretical number of weeks necessary
      to normalization that was called predicted time to normalization. Decline rates
      were classified into "favorable" or "unfavorable". Totally, 75 patients were
      identified, 39 had favourable (group A) and 36 unfavorable (group B) STMD. The 2
      year and 5-year PFS rates were 61% and 58% for group A and 17% and 7% group B
      (p<0.00001). Of all the baseline characteristics that were included in the Cox
      model, STMD was the most important predictor of PFS and OS. We suggest that STMD
      is strong independent prognostic factor in GCT patients treated with salvage
      chemotherapy. Prospective studies of different approaches in this patient's
      population based on STMD are warranted.

PMID- 19580342
TI  - Nuclear topography of the 1q21 genomic region and Mcl-1 protein levels associated
      with pathophysiology of multiple myeloma.
AB  - Chromosomal rearrangements and copy number variation are frequently observed in
      cancer cells, including multiple myeloma (MM). Karyotypic abnormalities seen in
      MM cells correlate with the disease stage and drug responses. Here, we
      investigate the nuclear arrangement of the 1q21 region; amplification of this
      region is an important diagnostic and prognostic marker of MM. We examined the
      lymphoblastoid cell line CD138- ARH-77, multiple myeloma CD138+ MOLP-8 cells, and
      the CD138+ bone marrow fraction of patients diagnosed with MM. In this
      experimental system, we observed that gamma-radiation and selected cytostatic
      drugs such as melphalan and dexamethasone did not significantly alter the nuclear
      radial arrangement of the 1q21 region and other relevant regions of chromosome 1.
      Similarly, conserved nuclear radial positioning after cytostatic treatment was
      observed for the c-myc, TP53, CCND1, and IgH loci. When analyzed Mcl-1, a protein
      encoded by a gene mapped to the 1q21 region, we found that the variant Mcl1S is
      highly expressed in multiple myeloma MOLP-8 cells, but not in peripheral blood
      lymphocytes of healthy donors or lymphoblastoid ARH-77 cells; this is in contrast
      to the expression pattern of the Mcl-1L variant. On the basis of these
      observations we suggest that the 1q21 region is an important diagnostic marker of
      MM, particularly the gene encoding the Mcl-1S variant, which can be easily
      detected by western analysis.

PMID- 19580343
TI  - Immunohistochemical markers of proliferation and vascularisation in preneoplastic
      bronchial lesions and invasive non-small cell lung cancer.
AB  - Autofluorescence bronchoscopy (AFB) has been shown to be sensitive to detect
      preneoplastic lesions in central lung airways system. In early stages of
      carcinogenesis, up-regulation of cyclooxygenase (COX)-2, Ki67 and/or increased
      angiogenesis may play a role by promoting the proliferation of tumoral cells and
      their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and
      setting up of the metastatic process. The present study compared the expression
      of proliferative (COX-2, Ki67 and PCNA) and angiogenic markers (CD34 and NG2)
      between preneoplastic bronchial squamous dysplasia lesions and invasive squamous
      cell carcinoma. Biopsies obtained during AFB [preneoplastic lesions: low-grade
      (lesions up to moderate dysplasia), n=13; high-grade lesions (severe dysplasia),
      n=12] and surgical specimens (resections of bronchogenic carcinoma, n=11) were
      stained with COX-2, Ki67, PCNA, CD34 and NG2 monoclonal antibodies. Microvessel
      density (MVD) was analysed based on anti-CD34 immunostaining. Lesions were
      positive for COX-2 in 12 out of 25 preneoplastic lesions, and in 10 out of 11
      invasive carcinomas (p=0.025). In preneoplastic lesions, the mean percentage of
      Ki67 positive cells was lower compared to invasive carcinomas (37.4+/-5.8 versus
      58.6+/-8.4%, p=0.043). In addition, significant differences in MVD were observed
      between preneoplastic and NSCLC specimen [35.3 (25.9, 61.9) versus 22.1 (20.1,
      32.6), p=0.016]. No differences were observed in the mean percentage of PCNA or
      NG2 positive cells between preneoplastic lesions and invasive carcinomas.
      Findings of the present study indicate that increases in COX-2 and Ki67
      expression may be associated with the development of bronchogenic carcinomas and
      possibly with acquisition of an invasive phenotype. In contrast, increased CD34
      expression in preneoplastic lesions suggests that increased MVD may represent an
      early marker of lung carcinogenesis.

PMID- 19580344
TI  - Polymorphisms of biotransforming enzymes (GSTs) and their association with
      colorectal cancer in the Slovak population.
AB  - The aim of present study was to summarize the results of a case-control study
      focused on genetic polymorphisms of selected Phase II metabolizing enzymes
      (GSTM1, T1, P1) and to investigate the association of these polymorphisms with
      the colorectal cancer risk among the Slovak population. A case-control study with
      183 colorectal cancer cases and 422 controls was conducted. DNA was extracted
      from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1
      enzymes were determined by PCR-based methods. Association between specific
      genotypes and the development of colorectal cancer were examined using logistic
      regression analysis to calculate odds ratios (OR) and 95% confidence intervals
      (CI). The GSTP1 val/val genotype (OR=2.1, 95%CI: 1.1 - 4.0, chi2 = 0.28 and P =
      0.0025) was associated with an elevated risk. The statistically significant
      correlation was found also for the combined genotypes of GSTM1 null and GSTP1
      valine homozygosity (OR = 2.7, 95% CI: 1.1-6.1, chi2 = 4.5 and P = 0.03). The
      genotype of certain metabolising enzymes affects the risk for colorectal cancer.
      This effect is also important when certain allelic combinations are studied. In
      the near future, individual risk assessment may be reached by further increasing
      the number of studies of polymorphisms, combining them with the traditional
      epidemiological risk factor.

PMID- 19580345
TI  - Acute lymphoblastic leukemia-derived dendritic cells express tumor associated
      antigens: PNPT1, PMPCB, RHAMM, BSG and ERCC1.
AB  - In all types of leukemia both in children and adults there is a need for novel
      therapies that could reduce the risk of relapse after standard treatment. Acute
      lymphoblastic leukemia (ALL) cells are ineffective antigen presenting cells, but
      as shown by many authors including results from our laboratory, stimulation with
      CD40L restores their antigen expressing capacity. The development of T-cell
      therapies for leukemic patients can be based on discovery of leukemia-associated
      antigens (LAA) which could be recognized by the host immune system. The aim of
      our present study was to test the hypothesis that leukemia-derived dendritic
      cells maintain the expression of tumor associated antigens. Twenty five children
      with B-cell precursor ALL were prospectively enrolled into the study. The
      mononuclear cells from peripheral blood or bone marrow were cultured and
      stimulated (or not) with CD40L and IL-4. The assessment of costimulatory/adhesion
      molecules with the use of flow cytometry and real-time RT PCR were used to
      confirm the possibility of turning ALL cells into dendritic-like cells.
      Additionally 22 tumor associated antigens mRNA levels were determined by real
      time PCR technique with the TaqMan chemistry using ready-to-use Low Density
      Arrays for Gene Expression. The results of the study showed maintained expression
      and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor
      associated antigens in CD40-activated leukemic cells. CD40L stimulation leading
      to the differentiation of leukemic cells into DCs which combine both antigen
      presenting function and expression of tumor associated antigens represents an
      interesting approach in cancer immunotherapy.

PMID- 19580346
TI  - Variation of bone marrow CD34+ cell subsets in myelodysplastic syndromes
      according to who types.
AB  - Bone marrow (BM) hematopoietic progenitor cells (CD34+) are a heterogeneous
      population with varying degrees of commitment and maturation to several cell
      lineages. In myelodysplastic syndromes (MDS), this population is increased. We
      examined the major cell types found in the blast gate by flow cytometry in newly
      diagnosed patients with MDS, compared them to normal BM and studied their
      variation according to WHO type. Two subsets defined by SSC were found both in
      normal BM and MDS, corresponding to myeloblasts and B-cell precursors. The number
      of B-cell precursors among all nucleated cells was equally low, independent of
      WHO type. However, the subset with an intermediate SSC, but CD117, CD13 and CD19
      negative increased with the rise of myeloblasts. Concomitantly, the ratio between
      CD34+/CD117+/CD34-/CD117+ cells was increased. These two features are consistent
      with the maturation block occurring in the progression of the neoplastic clone.
      We conclude that the quantitative analysis of the cell types present in the BM
      blast gate by flow cytometry is not only important for the diagnosis of MDS in
      patients with peripheral cytopenias and a normal karyotype, but gives also
      important prognostic information of the patients.

PMID- 19580347
TI  - Associations between hypoxia-inducible factor-1alpha (HIF-1alpha) gene
      polymorphisms and risk of developing breast cancer.
AB  - The C1772T, G1790A and C111A polymorphisms of Hypoxia-inducible factor-1alpha
      (HIF-1alpha) gene were analyzed in a hospital-based Malaysian population using
      PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from
      410 breast cancer patients and 275 normal and healthy women. We investigated the
      association between HIF-1alpha polymorphisms and breast cancer risk, and clinico
      pathological parameters in the population. The genotype and allele frequencies of
      C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between
      the breast cancer cases and normal subjects but similar association was not
      observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively.
      Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes
      (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI,
      1.13-2.43) were significantly associated with increased risk of breast cancer.
      Significant relationship was observed also between T allele and breast cancer
      risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that
      1772T allele genotype was significantly associated with nodal metastases
      (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05).
      Our observations suggest that the polymorphic allele of C1772T may be associated
      with increased risk of developing breast cancer, and presence of 1772T allele may
      be a useful genetic marker for tumor prognosis.

PMID- 19580348
TI  - Estrogen-dependent regulation of PPAR-gamma signaling on collagen biosynthesis in
      adenocarcinoma endometrial cells.
AB  - The link between estrogen and metabolic developmental factors of endometrial
      carcinoma is well established. PPAR- gamma, (an important modulator of
      metabolism) and estrogen receptor belong to a family of nuclear hormone receptors
      that were shown to interact with each other. The interaction may affect
      transcriptional activity of these transcription factors. The anti-diabetic
      troglitazone (TGZ) is well known PPAR- gamma ligand. The effect of troglitazone
      induced PPAR- gamma activation on estrogen-dependent stimulation of collagen
      biosynthesis was studied in the Ishikawa endometrial adenocarcinoma cell line. We
      have found that the presence of estrogen activity in growth medium (1nM)
      augmented collagen biosynthesis in the cells. An addition of PPAR- gamma
      agonists, as troglitazone or clofibrat to the growth medium induced inhibition of
      collagen biosynthesis. The inhibition was effective only when estrogen receptor
      was stimulated, since removal of estrogen receptor by ICI 182- 780-dependent
      degradation did not affect collagen biosynthesis. The mechanism of the inhibition
      was found at the level of NF-kB (known inhibitor of collagen gene expression) and
      MAPK signaling. PPAR- gamma ligands stimulated expression of NF-kB, while they
      inhibited expression of p-38 but not ERK1/ERK2. The data document for the first
      time that inhibitory effect of PPAR- gamma ligands on collagen biosynthesis in
      endometrial adenocarcinoma cells requires functional estrogen receptor.

PMID- 19580349
TI  - Clonal evolution in chronic lymphocytic leukemia studied by interphase
      fluorescence in-situ hybridization.
AB  - The results of repeated interphase fluorescence in-situ hybridization (I-FISH,
      FISH) examination of 97 CLL patients and correlation of these findings with IgVH
      hypermutation status, ZAP-70 and CD38 expression are presented. The appearance of
      new, FISH-detectable, genomic aberrations during disease course, described as
      clonal evolution (CE), was observed in 26% of patients. The most frequent newly
      acquired cytogenetic abnormality was 13q deletion in 64% (16/25). In contrast to
      earlier studies, there was no correlation found between CE and either one of
      single negative prognostic factors (unmutated IgVH; CD38 positivity; ZAP-70
      positivity). However, the combination of all three negative factors correlated
      with CE highly significantly (p=0.005) and moreover, also with a shift from lower
      to higher FISH risk category (p=0.010). As the prognostic data were known in all
      patients, this study represents the complete insight on the association of CE and
      other risk parameters in CLL.

PMID- 19580350
TI  - A whole population study of gastrointestinal stromal tumors in the Czech Republic
      and Slovakia.
AB  - Due to problems with identification and an incomplete understanding on the
      gastrointestinal stromal tumors (GIST) before 2001, there has been a lack of
      comprehensive long-term population-based studies on GIST epidemiology at present
      date. We used data from the online registry of Czech and Slovak GIST patients
      (http://gist.registry.cz/), which has been compiled and maintained since 2006 and
      involves patients diagnosed from the year 2000. 278 patients were included in
      this study. Most of the tumors fell into the high-risk category (58.7%), followed
      by the intermediate (21.4%), low (16.6%) and very low (3.3%) categories.
      Locations other than the small intestine and stomach had significantly higher
      contribution of high-risk tumors. The median time of overall survival was 93.2
      months, 5-year relative survival was 78.3% overall, 71.9% for patients with high
      risk tumors, 91.1% for intermediate patients, and 91.9% for patients from the low
      and very low-risk category. The annual crude incidence between the years 2001
      2005 was 0.52 cases per 100,000 inhabitants. The annual European ASR and World
      ASR were 0.44 and 0.31 per 100,000 inhabitants, respectively. Presented data
      generally correspond to the whole-population studies recently published,
      including actual data on epidemiology, clinical characteristics, and survival of
      patients. The registry helps in improving GIST diagnostics, knowledge about the
      properties and behaviour of tumors, communication among physicians, and, last but
      not least, therapeutical options and results.

PMID- 19580351
TI  - Laparoendoscopic single-site (LESS) nephrectomy through a Pfannenstiel incision:
      porcine model.
AB  - PURPOSE AND OBJECTIVE: Laparoscopic nephrectomy has become a standard of care for
      localized renal tumors. Several groups have demonstrated single-incision
      laparoscopic nephrectomy performed completely through the extraction site,
      including transumbilical, paramedian, and transvaginal incisions. The
      Pfannenstiel incision is a commonly used extraction site after laparoscopic
      radical nephrectomy. The advantages of this incision include improved cosmesis as
      well as decreased pain. We investigated the feasibility of performing a single
      incision laparoscopic nephrectomy through a Pfannenstiel incision in a porcine
      model, because this is the extraction site of choice at our institution.
      MATERIALS AND METHODS: Bilateral laparoscopic nephrectomies were performed in
      five acute female swine through a GelPort inserted into a 4- to 6-cm incision
      comparable to the human Pfannenstiel incision. RESULTS: Nine of 10 attempted
      nephrectomies were completed successfully. One nephrectomy was aborted because of
      a renal capsule laceration from a retraction injury. Mean operative time was 70.6
      minutes (range 49-120 min). Mean estimated blood loss was 29.4 mL (range 5-100
      mL). CONCLUSIONS: Laparoscopic nephrectomy through a single Pfannenstiel incision
      is technically feasible in the porcine model. We anticipate incorporating this
      approach in humans, because we commonly use the Pfannenstiel incision as an
      extraction site.

PMID- 19580352
TI  - Treatment time reduction using tandem shockwaves for lithotripsy: an in vivo
      study.
AB  - BACKGROUND AND PURPOSE: Reducing extracorporeal shockwave lithotripsy (SWL) time
      by increasing the shockwave rate of the lithotripter has been tested in the past;
      however, basic research and treatment outcomes revealed that this is not
      convenient. The purpose of this study was to use an animal model to demonstrate
      that SWL treatment time can be reduced significantly without sacrificing stone
      fragmentation efficiency using tandem shockwaves. MATERIALS AND METHODS: A tandem
      research lithotripter was used to treat 50 artificial kidney stones implanted
      into the kidneys of 50 rabbits. Standard single-pulse and tandem shockwaves were
      compared in two different scenarios: Without a fluid-filled expansion chamber and
      with a fluid-filled expansion chamber surrounding the stone. RESULTS: The
      presence of fluid surrounding the stone enhances fragmentation in both the
      standard and tandem modes. No significant difference in fragmentation efficiency
      was recorded between the standard and tandem SWL with stones surrounded by fluid;
      however, the treatment time with tandem shockwaves was reduced by 50%.
      CONCLUSIONS: Significantly shorter SWL treatments may be possible in the future
      using tandem shockwaves on urinary stones that are surrounded by fluid.

PMID- 19580353
TI  - Quantifying a strategic view of diabetes technology impacts: a system dynamics
      approach.
AB  - BACKGROUND: Diabetes and its related complications and comorbidities (C&Cs)
      represent a significant and increasing healthcare burden. Absence of a systematic
      manner to evaluate value propositions of technologies from various stakeholders'
      perspectives impedes the best uses of current and emerging technologies. METHODS:
      A system dynamics methodology was used to develop a comprehensive causal
      simulator of the U.S. population and give proof of principle that entire
      portfolios of present and future technologies can be evaluated for direct and
      indirect impacts. An explicit semiquantitative methodology was used for
      surveying, prioritizing, and grouping C&Cs, patient subgroups, and technologies,
      utilizing diverse publicly available clinical literature. RESULTS: The resulting
      model simulates the incidence and prevalence of diabetes and 10 of its most
      commonly associated C&Cs, reflecting their interrelated upstream and downstream
      relationships. The simulator enables systematic evaluation of tens of thousands
      of potential combinations of emerging technologies and technology leverage points
      that can be used to improve patient outcomes and guide technology investments.
      Feasibility was demonstrated through single, pair-wise, and targeted analyses of
      technologies. CONCLUSIONS: This effort demonstrated the feasibility of linking
      complex, interconnected disease states, impact points, outcomes, and
      interventions with a variety of outcome metrics, to an extent greater than
      existing models developed for other purposes. The project demonstrated the
      ability to identify priority technologies and pipeline therapies and leverage
      points among diabetes interventions. It demonstrated more effective knowledge
      management of diverse information essential for formulating strategy that could
      be applied in a wide range of therapeutic applications and technology innovation
      uses.

PMID- 19580354
TI  - Perceptions and attitudes are primary contributors to insulin delivery system
      satisfaction in people with type 2 diabetes.
AB  - BACKGROUND: This study identifies factors that influence satisfaction with an
      insulin delivery system (IDS). Knowledge of such factors could help identify
      individuals who would benefit from innovative IDS. METHODS: Individuals with type
      2 diabetes who use insulin, recruited from a general and chronic illness panel,
      participated in a web-based survey that included questions about demographics,
      self-reported diagnoses and hemoglobin A1c (HbA1c), current IDS used, insulin
      therapy attitudes, current IDS features, and satisfaction with IDS. Univariate
      analyses identified variables associated with IDS satisfaction (P < 0.05); those
      variables were entered into stepwise linear regression analyses with IDS
      satisfaction as the dependent variable. RESULTS: Six hundred sixty-seven
      individuals with type 2 diabetes participated (mean age, 57 years; 52% female;
      88% Caucasian; 73% vial/syringe users, 27% insulin pen users). IDS satisfaction
      was associated (P < 0.05) with gender, health status, HbA1c, self-reported
      comorbidity, insulin therapy attitudes, IDS type, and evaluation of IDS features.
      Among individuals who reported their HbA1c (n = 438), the best predictors of IDS
      satisfaction were perceived effectiveness and value of insulin therapy,
      evaluation of IDS activity interference, and commitment to insulin therapy (R2 =
      0.49, P < 0.001). Among all participants (n = 667), a second regression analysis
      that employed a variable representing report of HbA1c found the best predictors
      of IDS satisfaction included those in the first analysis with the addition of
      gender, report of HbA1c, and evaluation of IDS ease of use. These variables
      provided additional variance (R2 = 0.56, P < 0.001). CONCLUSIONS: In people with
      type 2 diabetes, positive perceptions and attitudes about insulin therapy have
      greater influence than the type of IDS used on IDS satisfaction.

PMID- 19580355
TI  - Exubera inhaled insulin in patients with type 1 and type 2 diabetes: the first 12
      months.
AB  - BACKGROUND: Following National Institute for Clinical Excellence approval of
      inhaled insulin Exubera (Pfizer, New York, NY) in 2006, we established a
      dedicated clinic in January 2007 to monitor the efficacy and safety of Exubera.
      Between January and October 2007, eight patients started Exubera: six because of
      needle phobia (DSM-IV criteria) and two with injection site problems. METHODS:
      Data were collected at the clinic over a 12-month period from February 2007 at 3
      , 6-, 9-, and 12-month intervals. The clinic is jointly led by a consultant
      diabetologist and a diabetes specialist nurse within the secondary care setting.
      RESULTS: Inhaled insulin was well tolerated in all eight patients who had
      previously experienced significant problems with initiation or intensification of
      subcutaneous insulin injections. Mean hemoglobin A1c was 10.7% (range, 8.1-14.2%)
      at initiation, 8.3% (7.2-9.4%) at 3 months, 7.7% (6.9-9.0%) at 6 months, 7.4%
      (6.7-8.4%) at 9 months, and 7.5% (6.5-8.7%) at 12 months. At 6 months, six
      patients had a reduction in forced expiratory volume in the first second (FEV1)
      by 4-12%, whereas five patients had a reduction of 2-12% at 12 months. One
      developed dyspnea, with a 29% fall in FEV1, which was transient and secondary to
      an upper respiratory tract infection. Two patients with the highest starting and
      most improved hemoglobin A1c developed significant retinopathy. CONCLUSIONS: Our
      12-month audit data demonstrate that the initiation of inhaled insulin in this
      difficult-to-treat group of patients resulted in a significant improvement in
      glycemic control. The subsequent withdrawal of an alternative and acceptable form
      of insulin treatment now presents a renewed challenge for our patients and
      healthcare professionals.

PMID- 19580356
TI  - Telemedicine influence on the follow-up of type 2 diabetes patients.
AB  - OBJECTIVE: This study was designed to evaluate the impact of a teleassistance
      system on the metabolic control of type 2 diabetes patients. RESEARCH DESIGN AND
      METHODS: We conducted a 1-year controlled parallel-group trial comparing patients
      randomized (1) to an intervention group, assigned to a teleassistance system
      using real-time transmission of blood glucose results, with immediate reply when
      necessary, and telephone consultations, or (2) to a control group, being
      regularly followed-up at their healthcare center. Study subjects were type 2
      diabetes patients >30 years of age followed in the primary care setting. RESULTS:
      A total of 328 type 2 diabetes patients were recruited from 35 family practices
      in the province of Malaga, Spain. There was a reduction in hemoglobin A1c after
      12 months from 7.62 +/- 1.60% to 7.40 +/- 1.43% (P = 0.027) in the intervention
      group and from 7.44 +/- 1.31% to 7.35 +/- 1.38% (P = 0.303) in the control group.
      The difference in the change between groups was not statistically significant.
      There was also a significant decrease in systolic and diastolic blood pressure,
      total cholesterol, low-density lipoprotein cholesterol, and body mass index in
      the intervention group. In the control group, the only significant decline was in
      low-density lipoprotein cholesterol. CONCLUSIONS: A teleassistance system using
      real-time transmission of blood glucose results with an option to make telephone
      consultations is feasible in the primary care setting as a support tool for
      family physicians in their follow-up of type 2 diabetes patients.

PMID- 19580357
TI  - The prescription of insulin pen devices versus syringes for older people with
      diabetes.
AB  - BACKGROUND: Insulin pen devices are easier to use and lead to better treatment
      adherence than syringes. This study sought to determine factors associated with
      the decision to prescribe insulin pen devices rather than syringes for older
      patients initiating insulin therapy. METHODS: A population-based study examined
      all Ontario, Canada residents > or = 66 years old who received a first
      prescription for insulin between 1998 and 2006 (n = 47,810). Associations between
      demographic/clinical factors and the use of pen devices for insulin delivery were
      determined. RESULTS: Seventy-two percent of patients began insulin therapy using
      pen devices for insulin delivery, increasing from 46% in 1998 to 86% in 2006.
      Insulin initiation by a specialist was positively associated with the use of pen
      devices (odds ratio [OR] 2.24, 95% confidence interval [CI] 2.08-2.40), whereas
      long-term care residence (OR 0.51, 95% CI 0.49-0.54) and initiation during
      hospitalization (OR 0.74, 95% CI 0.71-0.78) were negatively associated.
      CONCLUSIONS: Insulin pen devices were used by most patients starting insulin, but
      a substantial proportion of patients continued to be prescribed syringes for
      insulin delivery. The use of pen devices was positively associated with
      specialist care and negatively associated with insulin initiation during
      hospitalization. Increasing physicians' awareness of the benefits of pen devices
      to facilitate patient self-management could further increase their use and
      improve diabetes care.

PMID- 19580358
TI  - Transfection of rat pancreatic islet tissue by polymeric gene vectors.
AB  - BACKGROUND: In vitro genetic modification has been regarded as one option to
      improve the viability and functionality of pancreatic islets when used for
      transplantation in patients with diabetes, either as naked islets or in a type of
      bioartificial pancreas. In this approach, vector safety and poor transfection
      efficiency are major concerns. METHODS: In this study, the influence of in vitro
      transfection conditions on polyplexes constructed of polyethyleneimine (PEI) and
      plasmid DNA (pDNA) on the transfection efficiency was investigated by varying the
      transfection medium, the pDNA dose, and the amines of polycation/phosphates of
      pDNA (N/P) ratio. RESULTS: Ca2+-containing Krebs-Ringer-HEPES medium was more
      effective than RPMI 1640 medium by increasing transfection efficiency (2.5-fold).
      An increase in pDNA dose slightly reduced the transfection efficiency but had
      minimal influence on islet loss. However, the N/P ratio had a large effect on
      islet viability and transfection efficiency. For example, the PEI/pDNA ratio at
      N/P = 10 caused greater islet loss (56% vs. 28%) and 30-fold less transfection
      efficiency than at N/P = 5. Even under a set of best conditions selected from
      this study, mostly a fraction of cells located in the peripheral regions of an
      islet were transfected, and the viability and insulin secretion from the treated
      islets were not altered. However, it was found that the extent of apoptosis was
      noticeably higher (approximately 16%) than in untreated islets (approximately
      2%). CONCLUSIONS: These results suggest that the gene delivery efficacy to
      isolated islets can be improved by manipulating the transfection conditions.
      Polymeric vectors will broaden the options for islet transfection, which is
      currently limited to viral vectors.

PMID- 19580359
TI  - Enhanced cholinergic response in pancreata of nonhuman primates with impaired
      glucose tolerance shown on [18F]fluorobenzyltrozamicol positron emission
      tomography.
AB  - BACKGROUND: Islet cell adaptation to insulin resistance in type 2 diabetes
      mellitus may be due in part to increased stimulation of beta cells by the
      autonomic nervous system. The parasympathetic neurotransmitter acetylcholine
      (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells.
      The vesicular ACh transporter (VAChT) receptor correlates with cholinergic
      activity in vivo. The positron emission tomography (PET) radiotracer (+)-4
      [18F]fluorobenzyltrozamicol ([18F]FBT) binds to the VAChT receptor on presynaptic
      cholinergic neurons and can be quantified by PET. In this study, we utilize
      [18F]FBT PET to demonstrate pancreatic cholinergic activity before and after
      dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT)
      glucose tolerance. METHODS: Seven adult female vervet (Chlorocebus aethiops)
      monkeys were maintained on an atherogenic Western diet. They were divided into
      two groups: four with NGT and three with IGT. Each subject underwent [18F]FBT PET
      twice: first, a baseline PET under fasting conditions; and second, PET under
      fasting conditions but after intravenous infusion of dextrose solution.
      Quantitative analysis of pancreatic uptake at 60 min post-injection was
      performed. RESULTS: There was no difference in pancreatic uptake of [18F]FBT on
      baseline scans between the two groups. Pancreatic uptake of [18F]FBT increased in
      every subject after dextrose infusion (P = 0.03). On post-dextrose PET scans,
      pancreatic uptake of [18F]FBT was significantly higher in IGT subjects compared
      with NGT subjects (P = 0.03). The post-dextrose to pre-dextrose uptake ratios
      were higher in IGT subjects (P = 0.08). CONCLUSIONS: Acute increases in
      pancreatic cholinergic activity in vivo were detected in the pancreata of
      nonhuman primates with NGT and IGT after intravenous dextrose infusion on
      [18F]FBT PET. In subjects with IGT, this activity was significantly higher,
      suggesting increased autonomic nervous system stimulation of the pancreatic
      islets in insulin-resistant subjects.

PMID- 19580360
TI  - Daily glucose profiles in Japanese people with normal glucose tolerance as
      assessed by continuous glucose monitoring.
AB  - BACKGROUND: Little information is available regarding glucose fluctuations in
      postprandial states and during the oral glucose tolerance test (OGTT) in Japanese
      people with normal glucose tolerance (NGT). METHODS: Glucose profiles of 27
      Japanese people were measured for 4 days by using continuous glucose monitoring.
      A 75-g OGTT was conducted on the second day, and 24 subjects diagnosed with NGT
      by a 75-g OGTT were enrolled. The subjects were monitored for their postprandial
      glucose profile in their ordinary daily life on the third day. RESULTS: The
      results of our study have shown that the median time (interquartile range) to
      maximum glucose levels in OGTT was 38 (25-49) min after glucose load and that the
      median time to maximum glucose levels after breakfast, lunch, and dinner was 40
      (31-75), 50 (30-70), and 45 (36-50) min, respectively. The median increase in
      glucose during OGTT was 45 (35-66) mg/dL, and that after breakfast, lunch and
      dinner was 21 (12-32), 37 (27-48), and 44 (25-63) mg/dL, respectively. Those with
      a higher insulinogenic index reached their maximum glucose levels in a shorter
      time (r = -0.46, P = 0.025) and had smaller glucose increments during OGTT (r = 
      0.49, P = 0.014). CONCLUSIONS: This study is the first report to document the
      glucose profile of Asian people with NGT.

PMID- 19580361
TI  - Galvanic skin resistance--a marker for endothelial damage in diabetes.
AB  - BACKGROUND: Aging and diabetes are both associated with impaired vascular
      endothelial function. This causes a reduction in the resting blood flow and the
      blood flow response to autonomic stressors. Further, skin moisture and the
      ability to sweat are also reduced with aging and diabetes. The present
      investigation was undertaken to determine if the extent of damage from aging and
      diabetes could be accurately assessed by simply examining the electrodermal skin
      response (galvanic skin resistance) to a thermal stress. STUDY DESIGN: Forty-five
      subjects whose average age was 31.2 +/- 8.3 years (younger group), 62.4 +/- 9.6
      years (older group), and 61.8 +/- 11.3 years (diabetes group) were divided into
      three groups of 15 subjects. Subjects were exposed to environmental temperatures
      of 15 degrees C, 23 degrees C, or 32 degrees C for 30 min. During this period of
      time, sweat rate, skin blood flow, the electrodermal skin response, and skin
      moisture were measured. RESULTS: There were significant impairments in skin
      moisture, sweat, skin blood flow, and the galvanic skin response at any of the
      three environmental temperatures in subjects with diabetes compared to older
      subjects compared to younger subjects (analysis of variance, P < 0.01). Both a
      reduction in skin blood flow and impaired sweating contributed to the higher
      galvanic skin resistance seen in subjects with diabetes. The greatest contributor
      was impaired sweating. CONCLUSIONS: The results show that galvanic skin
      resistance, at any environmental temperature, may be a good means of assessing
      vascular damage and impaired sweat response in people with diabetes.

PMID- 19580362
TI  - Change in glucometer settings as a cause of sudden deterioration of glycemic
      control in type 2 diabetes.
AB  - The subject matter of this case report is "sudden deterioration" of glycemic
      control in a thus far well-complying patient with type 2 diabetes. It describes
      possible impacts of glucometer technical failure associated with other
      unfavorable circumstances. An error in displaying glycemia was discovered when
      analyzing data from glucometer in a computer using software (DIABASS PRO,
      Mediaspect GmbH, Konstanz, Germany) for data evaluation, and other possible
      complications (especially hypoglycemia episodes) resulting from inadequate
      treatment correction were thus prevented.

PMID- 19580364
TI  - Endovenous laser therapy of the small saphenous vein: patient satisfaction and
      short-term results.
AB  - OBJECTIVE: Conventional surgical treatment for small saphenous vein (SSV) reflux
      is associated with high recurrence rates and complications. Endovenous laser
      ablation (EVLA) is a treatment modality with promising results. This study
      reports patient satisfaction and short-term results after EVLA of SSV reflux.
      METHODS: Fifty-two legs of 49 consecutive patients were treated with EVLA for
      reflux of the SSV. Patients were investigated clinically and by duplex scanning
      before and 6 weeks after treatment. Patient records were studied and a
      questionnaire was completed. RESULTS: Technical success was accomplished in all
      patients. After 6 weeks the occlusion rate was 100% and after 6.5 months no
      recurrent varicosities were reported. Complications consisted of bruising (51%),
      induration (39%), delayed tightness (16%), phlebitis (2%), and temporary
      paresthesia (6%) and were all self-limiting. One deep venous thrombosis occurred
      in a patient with a protein C deficiency. Ninety-two percent (45/49) of patients
      were satisfied with the results and in 98% symptoms had significantly improved or
      completely disappeared. Working activities were resumed after a mean of 4 days.
      Forty-three patients (88%) would consider having endovenous laser treatment again
      if indicated. CONCLUSIONS: EVLA of the SSV seems to be a safe modality with
      excellent short-term results and high patient satisfaction. Controlled studies
      assessing the effectiveness of EVLA in comparison to conventional treatment of
      SSV reflux are crucial before considering EVLA as the standard treatment.

PMID- 19580365
TI  - Demographic differences in stage at diagnosis and cervical cancer survival in New
      Zealand, 1994-2005.
AB  - OBJECTIVE: To investigate ethnic, socioeconomic, and urban/rural differences in
      stage at diagnosis and cervical cancer survival in New Zealand. METHODS: The
      study involved 1594 cervical cancer cases registered during 1994-2005. Cox
      regression was used to estimate adjusted cervical cancer mortality hazard ratios
      (HRs). RESULTS: Maori and Pacific women had higher death rates than Other
      (predominantly European) women, with age and year of diagnosis adjusted HRs of
      2.15 (95% CI 1.68-2.75) and 1.98 (95% CI 1.25-3.13), respectively, whereas Asian
      women had a lower (nonstatistically significant) risk (0.81, 95% CI 0.47-1.42).
      Adjustment for stage reduced the HR in Maori to 1.62 (95% CI 1.25-2.09), but
      there was little change for Pacific or Asian women. These patterns varied over
      time: for cases diagnosed during 1994-1997, the HR for Maori women was 2.34 (95%
      CI 1.68-3.27), which reduced to 1.83 (95% CI 1.29-2.60) when adjusted for stage;
      for cases diagnosed during 2002-2005, the corresponding estimates were 1.54 (95%
      CI 0.75-3.13) and 0.90 (95% CI 0.43-1.89). Socioeconomic status and urban/rural
      residence had only marginal effects. CONCLUSIONS: There were major ethnic
      differences in cervical cancer survival in New Zealand that were only partly
      explained by stage at diagnosis. These patterns varied over time, with
      postdiagnostic factors playing an important role in the high Maori mortality
      rates in the 1990s, but in more recent years, the excess mortality in Maori women
      appeared to be almost entirely due to stage at diagnosis, indicating that ethnic
      differences in access to and uptake of screening and treatment of premalignant
      lesions may have been playing a major role.

PMID- 19580366
TI  - Evaluating preference-sensitive care for uterine fibroids: it's not so simple.
AB  - BACKGROUND: Preference-sensitive care decisions should reflect an informed
      patient's preferences. This retrospective survey of women with fibroids, a benign
      condition with multiple treatment options, sought to evaluate the extent to which
      this was measurable and true. METHODS: All 260 women in one medical group with
      visit codes for uterine fibroids during a 9-month period in 2006 were mailed
      surveys constructed through focus groups with physicians and interviews with
      patients. Correlations tested associations among their preferences, knowledge,
      and treatment decisions. RESULTS: The adjusted response rate was 82%, but only
      100 respondents fit all criteria for analysis. Nearly all wanted to either share
      or control the decision, and 86% felt informed, satisfied, and that the decision
      was consistent with their values. However, only 55% of patients could answer at
      least five of seven fibroid questions correctly. Hysterectomy use was
      significantly correlated with desire to relieve symptoms, have a permanent
      treatment, and do something right away (r = 0.36, 0.37, and 0.30, respectively).
      Those deciding not to treat were significantly less likely to have these
      preferences (r = -0.65, -0.40, and -0.58). These relationships were not affected
      by patient knowledge level, but patients with high knowledge scores were
      significantly more likely to believe their decision was concordant with their
      preferences (94.9% vs. 74.4%, p < 0.01). CONCLUSIONS: There were knowledge gaps
      but unclear associations between knowledge and decision-preference relationships
      for this condition, which has many different treatment alternatives. A
      prospective intervention trial is needed to determine if better information and
      counseling would produce stronger concordance between treatment selected and
      patient preferences.

PMID- 19580367
TI  - Propagation and breakup of liquid menisci and aerosol generation in small
      airways.
AB  - BACKGROUND: Droplets exhaled during normal breathing and not associated with
      coughing may pose hazardous agents to infective diseases dissemination. The
      objective is to explore the physical mechanism, which may lead to droplets
      formation. METHODS: We hypothesize that liquid menisci occlusions, which may form
      inside small airways, travel along the airway, may lose mass and finally
      disintegrate into small droplets. This hypothesis was numerically investigated
      applying physiologically plausible values of the phenomenological coefficients
      and geometrical conformations. RESULTS: We show that three important
      dimensionless parameters control the motion and disintegration of menisci: the
      dimensionless mucus layer thickness, the dimensionless menisci initial thickness
      (all scaled by the airway radius), and the capillary number. Menisci traveling
      within airways may either remain at equilibrium or diminish or increase in size.
      Menisci that diminish in size may collapse into the mucus layer; form a large
      droplet that contains most of the menisci mass before disintegration; or form a
      larger number of small droplets (we show the forming of three or four droplets in
      a single occluded airway). CONCLUSIONS: A critical capillary number for menisci
      at equilibrium could be defined. It was shown that menisci tend to diminish in
      size as the capillary number increases above the critical value, and a number of
      small droplets may be formed during normal breathing.

PMID- 19580368
TI  - Inhaled cyclosporine and pulmonary function in lung transplant recipients.
AB  - BACKGROUND: Chronic rejection, manifesting as bronchiolitis obliterans, is the
      leading cause of death in lung transplant recipients. In our previously reported
      double-blinded, placebo-controlled trial comparing inhaled cyclosporine (ACsA) to
      aerosol placebo, the rate of bronchiolitis-free survival improved. However, an
      independent analysis of pulmonary function, a secondary endpoint of the trial,
      was not performed. We sought to determine the effect of ACsA, in addition to
      systemic immunosuppression, on pulmonary function. METHODS: From 1998-2001, 58
      patients were randomly assigned to inhale either 300 mg of ACsA (28 patients) or
      placebo aerosol (30 patients) 3 days a week for the first 2 years after
      transplantation. Longitudinal changes in pulmonary function of ACsA patients were
      compared to aerosol placebo patients. In another analysis, the rate of decline
      from 6-month maximum FEV(1) in randomized patients was compared to the rate of
      decline in patients receiving conventional immunosuppression from the Novartis
      transplant database (644 patients, 12 centers worldwide, transplanted from 1990
      1995). RESULTS: The average duration of ACsA and aerosol placebo was 400 days +/-
      306 and 433 +/- 256, respectively. The change in FEV(1) of ACsA patients
      (adjusted for Cytomegalovirus (CMV) mismatch and transplant type, followed for a
      maximum duration of 4.6 years) was superior to the aerosol placebo controls (9.0
      +/- 71.4 mL/year vs. -107.9 +/- 55.3, p = 0.007). The FEF(25-75) decreased by 
      220.3 +/- 117.7 L/(second x year) vs. -412.2 +/- 139.2, p = 0.07, respectively.
      Similarly, percent FEV(1) decline from maximal values was improved in ACsA
      patients compared to aerosol placebo and Novartis controls (ACsA -0.43 +/-
      1.12%/year vs. aerosol placebo -4.08 +/- 1.4, p = 0.04; ACsA vs. Novartis -4.7 +/
      0.31, p = 0.007). Single-lung recipients receiving ACsA showed improvement in
      FEV(1) compared to Novartis controls (FEV(1) -0.8 +/- 1.8%/year vs. -4.94 +/-
      0.4, p = 0.03) but double-lung recipients showed improvement compared to aerosol
      placebo controls only (FEV(1) -0.28 +/- 1.22%/year vs. -8.53 +/- 5.95, p =
      0.048). CONCLUSIONS: In this single center trial, ACsA appears to ameliorate
      important pulmonary function parameters in lung transplant recipients compared to
      aerosol placebo and historical control patients. Single- and double-lung
      transplant recipients may not respond uniformly to treatment, and ongoing
      randomized trials in lung transplant recipients using ACsA may help elucidate our
      findings.

PMID- 19580369
TI  - Left-to-right asymmetry of aerosol deposition after shallow bolus inhalation
      depends on lung ventilation.
AB  - BACKGROUND: After shallow bolus inhalation of radiolabeled aerosols, gamma camera
      imaging has shown a left-right asymmetry, with a higher fraction of deposited
      particles in the left lung. It was not clear, however, whether this phenomenon
      was an effect of asymmetry in lung ventilation or aerosol deposition efficiency.
      METHODS: Lung ventilation and aerosol deposition was studied after shallow bolus
      inhalation and gamma camera imaging in nine healthy nonsmokers and 10
      asymptomatic smokers. A 100-mL (81m)Kr-gas boli were administered within the
      Fowler and within the phase-1 dead space, respectively. In addition, 1-L full
      breaths of 81m-Kr-gas were inhaled. For aerosol deposition subjects inhaled 100
      mL boli of 100-nm diameter radiolabeled carbon particles with shallow and deep
      penetration. Left-to-right (L/R) and central-to-peripheral (C/P) activity
      distribution of the lung was analyzed. RESULTS: None of the parameters analyzed
      were significantly different between nonsmokers and smokers. The full-breath 81m
      Kr-gas inhalation revealed a similar activity distribution over the left and
      right lungs, according to their respective volumes (L/R ratio = 0.84 +/- 0.04;
      mean +/- SE). In contrast, the shallow bolus inhalation of 81m-Kr-gas to the
      phase-1 dead space revealed more activity in the left lung (L/R ratio = 1.49 +/-
      0.15, normalized to full-breath Kr-gas L/R). This same left-right asymmetry was
      observed for the aerosol after shallow bolus inhalation (L/R ratio = 1.69 +/-
      0.15), and there was no significant difference between Kr-gas and aerosol L/R
      ratio. C/P activity ratios of bolus inhalation to the phase-1 dead space were
      1.71 +/- 0.19 and 1.79 +/- 0.15 (normalized to full-breath Kr-gas C/P) for gas
      and aerosol, respectively, and correlated with the L/R ratios. CONCLUSIONS: The
      data show that the asymmetry in shallow aerosol bolus deposition is primarily
      determined by lung ventilation. The reason for this asymmetry is unclear.

PMID- 19580370
TI  - Generation of immunogenic dendritic cells from human embryonic stem cells without
      serum and feeder cells.
AB  - AIM: Dendritic cell (DC)-based vaccines have a potential utility for use in the
      treatment of malignancy. Human embryonic stem cells (hESCs) may provide a more
      cost-effective and reliable source of DCs for immunotherapy purposes, providing
      on-demand access for patients. METHOD: We developed a protocol to generate DCs
      from hESCs in vitro in the absence of serum and feeder cells. This protocol uses
      growth factors bone morphogenetic protein-4, granulocyte macrophage-colony
      stimulating factor (GM-CSF), stem cell factor and VEGF in serum-free media to
      generate hESC-derived monocytic cells. These cells are further differentiated to
      hESC-derived immature DCs with GM-CSF and IL-4, and matured to hESC-derived
      mature DCs with a maturation cocktail consisting of GM-CSF, TNF-alpha, IL-1beta,
      IFN-gamma and PGE2. RESULTS: This study demonstrates the applicability of our
      defined differentiation process in generating functional hESC-derived DCs from
      multiple hESC lines. We show that hESC-derived immature DCs phagocytose, process,
      and present antigen upon maturation. hESC-derived mature DCs express the
      maturation marker CD83, produce Th1-directing cytokine IL-12p70, migrate in
      response to chemokine, and activate both viral and tumor antigen-specific T-cell
      responses. CONCLUSION: We developed a chemically defined system to generate
      unlimited numbers of DCs from hESCs. Our results demonstrate that hESC-derived
      DCs generated from this process are immunogenic and have the potential to be used
      for DC immunotherapy.

PMID- 19580371
TI  - Pediatric allergy medications: review of currently available formulations.
AB  - BACKGROUND: Allergy affects about 50% of the pediatric population globally.
      Allergic rhinitis (AR), one form of allergy, causes considerable impairment in
      quality of life, including disruption of sleep and, in children, interference
      with school attendance and performance. SCOPE: Traditional formulations and
      delivery systems - tablets, capsules, or intranasal sprays - successfully used by
      adults for treatment of AR may not be as easily administered in children. Liquid
      oral medications are more readily taken by children but contain sugars and
      excipients; they can also be inconvenient with less accurate dosing and are
      associated with dental caries and gastrointestinal upset. METHODOLOGY: This
      review evaluated medications for treatment of AR currently available for
      pediatric patients and identified the attitudes of parents and health care
      professionals toward these medications. Guidelines from international
      organizations and governmental websites were reviewed for recommendations and
      product labeling requirements. A Medline search was conducted using the terms
      dyes, excipients, palatability, prescribing habits, sugar, among others.
      FINDINGS: In recent years, governmental regulatory agencies and professional
      organizations in Europe and the United States have recommended avoidance of sugar
      in pediatric medicines and required stricter labeling of their ingredients.
      Public awareness about the adverse effects of sugar and some excipients has also
      increased, and parents more frequently express the desire for safer and more
      convenient medicines for their children. In response, more sugar-free, dye-free
      liquid medicines and other formulations, such as granules, filmstrips, chewable
      tablets, fast-dissolving tablets, and drops, are becoming available for pediatric
      use. LIMITATIONS: Data from well-designed trials conducted in children for the
      treatment of AR are lacking. In addition, the possibility of a social response
      bias may exist for parents and physicians about sugar and other ingredients in
      children's medications. CONCLUSION: Treatment for AR is often long-term,
      particularly in persistent AR; therefore, safety, tolerability, convenience, and
      patient/parental acceptance are important considerations when deciding which
      medication to prescribe.

PMID- 19580372
TI  - Parental attitudes toward new dosage forms of desloratadine in an online survey:
      results from four European countries.
AB  - BACKGROUND: Allergic disease affects an estimated 50% of children worldwide and
      causes considerable impairment in academic performance and daily activities.
      Pediatric formulations for allergy treatment are often highly sugared or contain
      ingredients to improve palatability, appearance, and patient
      acceptance/adherence. These excipients, however, are associated with dental
      caries, gastrointestinal intolerance, and dermatologic reactions. OBJECTIVE: To
      assess the appeal of new sugar-free/dye-free syrup and orodispersible
      formulations of the second-generation antihistamine desloratadine to parents of
      children with allergy in four European countries. DESIGN: In an online survey of
      households with children aged < or =12 years with allergies in France, Italy, the
      Netherlands, and Spain, respondents were asked to consider one of two
      desloratadine product concepts: a sugar-free, dye-free oral solution or an
      orodispersible tablet. PARTICIPANTS: Eligible households had to have at least one
      child aged < or =12 years with symptomatic seasonal, pet, or indoor allergies or
      hives for > or =1 week/year. Respondents had to be the decision makers regarding
      their child's allergy medication and to be likely to treat symptoms with
      prescription medication some of the time. RESULTS: There were 627 eligible
      households. Most (88%) parents in Spain were likely to ask their physician about
      and to consider trying sugar-free, dye-free desloratadine syrup, followed by 76%
      of those in France, 68% in Italy, and 56% in the Netherlands. About three
      quarters of parents in France, Spain, and Italy and more than half of those in
      the Netherlands were likely to ask their physician about and to consider trying
      the orodispersible formulation. LIMITATIONS: There is no control group for
      comparisons between the study's online responses and those that would have
      resulted from another survey methodology. Further, response biases do exist
      across countries based on cultural norms. CONCLUSION: Survey respondents were
      generally receptive to the new sugar-free, dye-free syrup and orodispersible
      tablet formulations of the second-generation antihistamine desloratadine. At
      least half of parents surveyed indicated their willingness to try the new
      products.

PMID- 19580376
TI  - Generation of liposome aerosols with the Aeroneb Pro and the AeroProbe
      nebulizers.
AB  - BACKGROUND: Inhalation of therapeutic aerosols is a long-established means of
      drug delivery to the lungs or to the systemic circulation. In addition to
      solutions, suspensions, and particulates, liposomal formulations are being
      developed for aerosol administration. In this report, we investigated the
      membrane integrity of liposomes encapsulating the fluorescent model compound,
      calcein, after nebulization using two novel aerosolization devices, the Aeroneb
      Pro vibrating-mesh nebulizer (Aerogen, Dangan, Ireland) and the AeroProbe
      intracorporeal nebulizing catheter (Trudell Medical Corporation, London, Ontario,
      Canada). MATERIALS AND METHODS: The influence of lipid composition and
      lamellarity on the stability of the vesicles was investigated by measuring
      changes in median diameter, zeta-potential, and calcein retention. RESULTS: Both
      nebulizers were able to successfully aerosolise 1.5 mL of liposome suspension in
      a short period of time. The diameter and zeta-potential of the liposomes was
      preserved upon nebulization, and the calcein retention was above 70% in all
      cases. CONCLUSIONS: It can, hence, be concluded that both systems, the Aeroneb
      Pro and the AeroProbe, are well suited for the pulmonary delivery of liposomal
      formulations, with the AeroProbe having the additional advantage of allowing
      targeted delivery into the select regions of the lungs with a high degree of
      efficiency and control.

PMID- 19580375
TI  - Characterization of long-term cultured c-kit+ cardiac stem cells derived from
      adult rat hearts.
AB  - Previous studies have revealed c-kit-positive (c-kit(+)) cardiac stem cells
      (CSCs) in the adult mammalian heart and these cells could be a suitable cell
      source for heart regeneration therapy. However, these cells have not been fully
      evaluated in terms of characterization and effect of long-term culture, which is
      necessary for their safe and optimal usage. Therefore, we isolated c-kit(+) CSCs
      from adult rat hearts to characterize these cells and investigate stability over
      long-term culture. We performed isolations of c-kit(+) CSCs 11 times and passaged
      them 40 times in a bulk culture system; we termed these cultures, bulk culture
      CSCs (CSC-BC). c-kit(+) CSCs expressed stemness genes and exhibited stem cell
      properties of single cell-derived clone formation, cardiosphere generation, and
      potential to differentiate into the three main cardiac lineages: cardiomyocyte,
      smooth muscle, and endothelial cells in vitro. Over long-term culture, some CSC
      BC up-regulated GATA-4 expression, which resulted in enhanced cardiomyocyte
      differentiation, suggesting that the GATA-4 high c-kit(+) CSCs have potent
      cardiac regenerative potential. We also observed the spontaneous differentiation
      into cells other than cardiac lineages, such as adipocyte and skeletal myocyte.
      This effect of long-term culture on the c-kit(+) CSCs has not been previously
      reported. Interestingly, when c-kit(+) CSCs were co-cultured with adult rat
      cardiomyocytes, we found increased cardiomyocyte survival, and the growth
      factors, insulin-like growth factor 1 (IGF-1) and vascular endothelial growth
      factor (VEGF), appeared to be responsible factors. The present study suggests
      that c-kit(+) CSCs have great therapeutic potential yet should be further
      investigated and optimized as a cell source for regenerative therapies prior to
      transplantation.

PMID- 19580377
TI  - Prediction of segregation tendency in dry particulate pharmaceutical mixtures:
      Application of an adapted mathematical tool to cohesive and non-cohesive
      mixtures.
AB  - The measurement of average residence times and their variance, used to calculate
      the deviation of chemical reactors from the ideal behaviour of a perfectly-mixed
      vessel, or a plug flow pattern, has already been proposed in the literature to
      evaluate the segregation tendency of granular mixtures. The method consists of
      introducing pulse perturbation (of another material) to the established regular
      flow of a single granular material or a granular mixture and to assess the
      response of the system in terms of pulsed material concentration at the process
      outlet. The particles' average residence time and its standard deviation are then
      related to segregation tendency. Results from the application of this new method
      are useful when compared to those obtained from a reference mixture to be chosen
      according to a particular formulation development or process understanding need.
      This work applies the proposed method for various mixtures, both cohesive and non
      cohesive, and derives phenomenological mathematical models expressing segregation
      tendency as a function of the parameters shown to be critical (i.e. statistically
      significant) to component segregation. The models were shown to be statistically
      and experimentally robust in the case of non-cohesive to slightly cohesive
      mixtures. Although the mathematical models are phenomenological, the findings
      allow for deriving mechanistic explanations on segregation tendency.

PMID- 19580378
TI  - Interrogating 7TM receptors: does texture in the question yield greater texture
      in the answer?
AB  - The key to detecting and classifying drug effect at seven transmembrane (7TM)
      receptors is the pharmacological assay. Drug discovery had been rooted in testing
      of molecules on intact animal tissue until technology provided high-throughput
      binding assays for screening. While this allowed for the testing of large numbers
      of molecules, it also limited detection to molecules that interfere with the
      interaction of the receptor with a defined probe (i.e., radioligand). The ability
      to monitor functional changes in cells (recombinant or natural) provided a huge
      leap forward. Earlier functional assays were tied to specific signaling pathways
      (i.e., cyclic AMP and calcium) but now label-free assays in live cells provide
      the opportunity to detect more ligands and more fully characterize their
      efficacy. These ideas will be discussed in terms of harnessing the phenomenon of
      "functional selectivity" for therapeutic advantage.

PMID- 19580379
TI  - Growth factor-mediated hyper-elongation of glycosaminoglycan chains on biglycan
      requires transcription and translation.
AB  - The mechanism through which growth factors cause glycosaminoglycan (GAG) hyper
      elongation is unclear. We have investigated the role of transcription and
      translation on the GAG hyper-elongation effect of platelet-derived growth factor
      (PDGF) in human vascular smooth muscle cells (VSMCs). To determine if the
      response involves specific signalling pathways or the process of GAG hyper
      elongation we have also investigated the effects of epidermal growth factor
      (EGF), transforming growth factor-beta (TGF-beta) and thrombin. We report that
      both actinomycin D and cycloheximide completely abolished the ability of PDGF to
      stimulate radiosulphate incorporation and GAG elongation into secreted
      proteoglycans, and to increase the size of xyloside GAGs. Blocking de novo
      protein synthesis completely prevented the action of all growth factors tested to
      elongate GAG chains. These results lay a foundation for further investigation
      into the genes and proteins implicated in this response.

PMID- 19580380
TI  - Shared neural circuits for mentalizing about the self and others.
AB  - Although many examples exist for shared neural representations of self and other,
      it is unknown how such shared representations interact with the rest of the
      brain. Furthermore, do high-level inference-based shared mentalizing
      representations interact with lower level embodied/simulation-based shared
      representations? We used functional neuroimaging (fMRI) and a functional
      connectivity approach to assess these questions during high-level inference-based
      mentalizing. Shared mentalizing representations in ventromedial prefrontal
      cortex, posterior cingulate/precuneus, and temporo-parietal junction (TPJ) all
      exhibited identical functional connectivity patterns during mentalizing of both
      self and other. Connectivity patterns were distributed across low-level embodied
      neural systems such as the frontal operculum/ventral premotor cortex, the
      anterior insula, the primary sensorimotor cortex, and the presupplementary motor
      area. These results demonstrate that identical neural circuits are implementing
      processes involved in mentalizing of both self and other and that the nature of
      such processes may be the integration of low-level embodied processes within
      higher level inference-based mentalizing.

PMID- 19580381
TI  - Encoding in the visual word form area: an fMRI adaptation study of words versus
      handwriting.
AB  - Written texts are not just words but complex multidimensional stimuli, including
      aspects such as case, font, and handwriting style, for example.
      Neuropsychological reports suggest that left fusiform lesions can impair the
      reading of text for word (lexical) content, being associated with alexia, whereas
      right-sided lesions may impair handwriting recognition. We used fMRI adaptation
      in 13 healthy participants to determine if repetition-suppression occurred for
      words but not handwriting in the left visual word form area (VWFA) and the
      reverse in the right fusiform gyrus. Contrary to these expectations, we found
      adaptation for handwriting but not for words in both the left VWFA and the right
      VWFA homologue. A trend to adaptation for words but not handwriting was seen only
      in the left middle temporal gyrus. An analysis of anterior and posterior
      subdivisions of the left VWFA also failed to show any adaptation for words. We
      conclude that the right and the left fusiform gyri show similar patterns of
      adaptation for handwriting, consistent with a predominantly perceptual
      contribution to text processing.

PMID- 19580382
TI  - Electrophysiological evidence for different types of change detection and change
      blindness.
AB  - Numerous studies have demonstrated that observers often fail to notice large
      changes in visual scenes, a phenomenon known as change blindness. Some
      experiments have suggested that phenomenological experience in change blindness
      experiments is more diverse than the common distinction between change detection
      and change blindness allows to resolve. Recently, it has been debated whether
      changes in visual scenes can be detected ("sensed") without a corresponding
      perception of the changing object ("seeing") and whether these phenomena build on
      fundamentally different perceptual processes. The present study investigated
      whether phenomenologically different perceptual processes such as sensing and
      seeing rely on different or similar neural processes. We studied ERP effects of
      visual change processing (as compared to change blindness) when observers merely
      detected the presence of a change ("sensing") and when they identified the
      changing object in addition to detection ("seeing"). Although the visual
      awareness negativity (VAN)/selection negativity was similar for detection with
      and without identification, a change-related positivity and the N2pc
      contralateral to changes were found exclusively when the change was fully
      identified. This finding indicates that change identification requires perceptual
      and neural processes that are not involved in mere detection. In a second
      experiment, we demonstrated that the VAN and N2pc effects are similar to effects
      of selective attention in a visual search task. By contrast, the change-related
      positivity was specific for conscious processing of visual changes. The results
      suggest that changes can be detected ("sensed") without perception of the
      changing object. Furthermore, sensing and seeing seem to rely on different neural
      processes and seem to constitute different types of visual perception. These
      findings bear implications for how different categories of visual awareness are
      related to different stages in visual processing.

PMID- 19580383
TI  - Elucidating the nature of deregulated semantic cognition in semantic aphasia:
      evidence for the roles of prefrontal and temporo-parietal cortices.
AB  - Semantic cognition--semantically driven verbal and nonverbal behavior--is
      composed of at least two interactive principal components: conceptual
      representations and executive control processes that regulate and shape
      activation within the semantic system. Previous studies indicate that semantic
      dementia follows from a progressive yet specific degradation of conceptual
      knowledge. In contrast, multimodal semantic impairment in aphasic patients
      (semantic aphasia [SA]) reflects damage to the control component of semantic
      cognition [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke
      aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132
      2147, 2006]. The purpose of the present study was to examine the nature of the
      semantic control deficits in SA in detail for the first time. Seven patients with
      SA were tested on four comprehension and naming tasks that directly manipulated
      the requirement for executive control in different ways. In line with many
      theories of cognitive control, the SA patients demonstrated three core features
      of impaired control: (i) they exhibited poor on-line manipulation and exploration
      of semantic knowledge; (ii) they exhibited poor inhibition of strongly associated
      distractors; and (iii) they exhibited reduced ability to focus on or augment less
      dominant aspects of semantic information, although the knowledge itself remained
      and could be successfully cued by external constraints provided by the examiner.
      Our findings are consistent with the notion that the anterior temporal lobes are
      crucial for conceptual knowledge whereas the left prefrontal and temporo-parietal
      cortices, damaged in patients with SA, play a critical role in regulating
      semantic activation in a task-appropriate fashion.

PMID- 19580384
TI  - Predictive mechanisms in idiom comprehension.
AB  - Prediction is pervasive in human cognition and plays a central role in language
      comprehension. At an electrophysiological level, this cognitive function
      contributes substantially in determining the amplitude of the N400. In fact, the
      amplitude of the N400 to words within a sentence has been shown to depend on how
      predictable those words are: The more predictable a word, the smaller the N400
      elicited. However, predictive processing can be based on different sources of
      information that allow anticipation of upcoming constituents and integration in
      context. In this study, we investigated the ERPs elicited during the
      comprehension of idioms, that is, prefabricated multiword strings stored in
      semantic memory. When a reader recognizes a string of words as an idiom before
      the idiom ends, she or he can develop expectations concerning the incoming
      idiomatic constituents. We hypothesized that the expectations driven by the
      activation of an idiom might differ from those driven by discourse-based
      constraints. To this aim, we compared the ERP waveforms elicited by idioms and
      two literal control conditions. The results showed that, in both cases, the
      literal conditions exhibited a more negative potential than the idiomatic
      condition. Our analyses suggest that before idiom recognition the effect is due
      to modulation of the N400 amplitude, whereas after idiom recognition a P300 for
      the idiomatic sentence has a fundamental role in the composition of the effect.
      These results suggest that two distinct predictive mechanisms are at work during
      language comprehension, based respectively on probabilistic information and on
      categorical template matching.

PMID- 19580385
TI  - Dissociable neural effects of long-term stimulus-reward pairing in macaque visual
      cortex.
AB  - It has been proposed that perceptual learning may occur through a reinforcement
      process, in which consistently pairing stimuli with reward is sufficient for
      learning. We tested whether stimulus-reward pairing is sufficient to increase the
      sensorial representation of a stimulus by recording local field potentials (LFPs)
      in macaque extrastriate area V4 with chronically implanted electrodes. Two
      oriented gratings were repeatedly presented; one was paired with a fluid reward,
      whereas no reward was given at any other time. During the course of conditioning
      the LFP increased for the rewarded compared to the unrewarded orientation. The
      time course of the effect of stimulus-reward pairing and its reversal differed
      between an early and late interval of the LFP response: a fast change in the
      later part of the neural response that was dissociated from a slower change in
      the early part of the response. The fast change of the late interval LFP suggests
      that this late LFP change is related to enhanced attention during the
      presentation of the rewarded stimulus. The slower time course of the early
      interval response suggests an effect of sensorial learning. Thus, simple stimulus
      reward pairing is sufficient to strengthen stimulus representations in visual
      cortex and does this by means of two dissociable mechanisms.

PMID- 19580386
TI  - Syntactic unification operations are reflected in oscillatory dynamics during on
      line sentence comprehension.
AB  - There is growing evidence suggesting that synchronization changes in the
      oscillatory neuronal dynamics in the EEG or MEG reflect the transient coupling
      and uncoupling of functional networks related to different aspects of language
      comprehension. In this work, we examine how sentence-level syntactic unification
      operations are reflected in the oscillatory dynamics of the MEG. Participants
      read sentences that were either correct, contained a word category violation, or
      were constituted of random word sequences devoid of syntactic structure. A time
      frequency analysis of MEG power changes revealed three types of effects. The
      first type of effect was related to the detection of a (word category) violation
      in a syntactically structured sentence, and was found in the alpha and gamma
      frequency bands. A second type of effect was maximally sensitive to the syntactic
      manipulations: A linear increase in beta power across the sentence was present
      for correct sentences, was disrupted upon the occurrence of a word category
      violation, and was absent in syntactically unstructured random word sequences. We
      therefore relate this effect to syntactic unification operations. Thirdly, we
      observed a linear increase in theta power across the sentence for all
      syntactically structured sentences. The effects are tentatively related to the
      building of a working memory trace of the linguistic input. In conclusion, the
      data seem to suggest that syntactic unification is reflected by neuronal
      synchronization in the lower-beta frequency band.

PMID- 19580387
TI  - Patterns of brain activity supporting autobiographical memory, prospection, and
      theory of mind, and their relationship to the default mode network.
AB  - The ability to rise above the present environment and reflect upon the past, the
      future, and the minds of others is a fundamentally defining human feature. It has
      been proposed that these three self-referential processes involve a highly
      interconnected core set of brain structures known as the default mode network
      (DMN). The DMN appears to be active when individuals are engaged in stimulus
      independent thought. This network is a likely candidate for supporting multiple
      processes, but this idea has not been tested directly. We used fMRI to examine
      brain activity during autobiographical remembering, prospection, and theory-of
      mind reasoning. Using multivariate analyses, we found a common pattern of neural
      activation underlying all three processes in the DMN. In addition,
      autobiographical remembering and prospection engaged midline DMN structures to a
      greater degree and theory-of-mind reasoning engaged lateral DMN areas. A
      functional connectivity analysis revealed that activity of a critical node in the
      DMN, medial prefrontal cortex, was correlated with activity in other regions in
      the DMN during all three tasks. We conclude that the DMN supports common aspects
      of these cognitive behaviors involved in simulating an internalized experience.

PMID- 19580388
TI  - The involvement of occipital cortex in the early blind in auditory and tactile
      duration discrimination tasks.
AB  - Early blind participants outperform controls on several spatially oriented
      perceptual tasks such as sound localization and tactile orientation
      discrimination. Previous studies have suggested that the recruitment of occipital
      cortex in the blind is responsible for this improvement. For example,
      electroencephalographic studies showed an enlarged posterior negativity for the
      blind in these tasks compared to controls. In our study, the question was raised
      whether the early blind are also better at tasks in which the duration of
      auditory and tactile stimuli must be discriminated. The answer was affirmative.
      Our electroencephalographic data revealed an enlarged posterior negativity for
      the blind relative to controls. Source analyses showed comparable solutions in
      the case of auditory and tactile targets for the blind. These findings support
      the interpretation of these negativities in terms of a supramodal rather than a
      modality-specific process, although confirmation with more spatially sensitive
      methods seems necessary. We additionally examined whether the early blind are
      less affected by irrelevant tactile or auditory exogenous cues preceding auditory
      or tactile targets than controls. No differences in alerting and orienting
      effects of these cues were found between the blind and the controls. Together,
      our results support the view that major differences between early blind
      participants and sighted controls on auditory and tactile duration discrimination
      tasks relate to a late and likely supramodal process that takes place in
      occipital areas.

PMID- 19580389
TI  - Momentary fluctuations in allocation of attention: cross-modal effects of visual
      task load on auditory discrimination.
AB  - Even when our attention is dedicated to an important task, background processes
      monitor the environment for significant events. The mismatch negativity (MMN)
      event-related potential is thought to reflect such a monitoring process.
      Nevertheless, there is continuing debate concerning the susceptibility of the MMN
      to attentional manipulation. We investigated the trial-by-trial relationship
      between brain activity related to change detection, reflected in the MMN, and
      visual psychophysical performance--while varying task difficulty. We find that
      auditory change detection is indeed "automatic" in that MMN remains robust
      despite increasing (visual) task load. However, the MMN amplitude and latency are
      susceptible to both visual load and to momentary attentional fluctuations as
      reflected in success or failure to identify a following visual target. We
      conclude that background central auditory processing is sensitive to the demands
      of a visual task, and fluctuates based on moment-to-moment allocation of
      attentional resources to the visual task.

PMID- 19580390
TI  - Morphosyntactic processing in late second-language learners.
AB  - The goal of the present study was to investigate the electrophysiological
      correlates of second-language (L2) morphosyntactic processing in highly
      proficient late learners of an L2 with long exposure to the L2 environment. ERPs
      were collected from 22 English-Spanish late learners while they read sentences in
      which morphosyntactic features of the L2 present or not present in the first
      language (number and gender agreement, respectively) were manipulated at two
      different sentence positions-within and across phrases. The results for a control
      group of age-matched native-speaker Spanish participants included an ERP pattern
      of LAN-type early negativity followed by P600 effect in response to both
      agreement violations and for both sentence positions. The late L2 learner results
      included a similar pattern, consisting of early negativity followed by P600, in
      the first sentence position (within-phrase agreement violations) but only P600
      effects in the second sentence position (across-phrase agreement violation), as
      well as significant amplitude and onset latency differences between the gender
      and the number violation effects in both sentence positions. These results reveal
      that highly proficient learners can show electrophysiological correlates during
      L2 processing that are qualitatively similar to those of native speakers, but the
      results also indicate the contribution of factors such as age of acquisition and
      transfer processes from first language to L2.

PMID- 19580391
TI  - Temporal aspects of the feeling of familiarity for music and the emergence of
      conceptual processing.
AB  - We tested whether the emergence of familiarity to a melody may trigger or co
      occur with the processing of the concept(s) conveyed by emotions to, or semantic
      association with, the melody. With this objective, we recorded ERPs while
      participants were presented with highly familiar and less familiar melodies in a
      gating paradigm. The ERPs time locked to a tone of the melody called the
      "familiarity emergence point" showed a larger fronto-central negativity for
      highly familiar compared with less familiar melodies between 200 and 500 msec,
      with a peak latency around 400 msec. This latency and the sensitivity to the
      degree of familiarity/conceptual information suggest that this component was an
      N400, a marker of conceptual processing. Our data suggest that the feeling of
      familiarity evoked by a musical excerpt could be accompanied by other processing
      mechanisms at the conceptual level. Coupling the gating paradigm with ERP
      analyses might become a new avenue for investigating the neurocognitive basis of
      implicit musical knowledge.

PMID- 19580392
TI  - fMRI activation during observation of others' reach errors.
AB  - When exposed to novel dynamical conditions (e.g., externally imposed forces),
      neurologically intact subjects easily adjust motor commands on the basis of their
      own reaching errors. Subjects can also benefit from visual observation of others'
      kinematic errors. Here, using fMRI, we scanned subjects watching movies depicting
      another person learning to reach in a novel dynamic environment created by a
      robotic device. Passive observation of reaching movements (whether or not they
      were perturbed by the robot) was associated with increased activation in fronto
      parietal regions that are normally recruited in active reaching. We found
      significant clusters in parieto-occipital cortex, intraparietal sulcus, as well
      as in dorsal premotor cortex. Moreover, it appeared that part of the network that
      has been shown to be engaged in processing self-generated reach error is also
      involved in observing reach errors committed by others. Specifically, activity in
      left intraparietal sulcus and left dorsal premotor cortex, as well as in right
      cerebellar cortex, was modulated by the amplitude of observed kinematic errors.

PMID- 19580393
TI  - Electrophysiological evidence for endogenous control of attention in switching
      between languages in overt picture naming.
AB  - Language switching in bilingual speakers requires attentional control to select
      the appropriate language, for example, in picture naming. Previous language
      switch studies used the color of pictures to indicate the required language
      thereby confounding endogenous and exogenous control. To investigate endogenous
      language control, our language cues preceded picture stimuli by 750 msec. Cue
      locked event-related potentials (ERPs) were measured while Dutch-English
      bilingual speakers overtly named pictures. The response language on consecutive
      trials could be the same (repeat trials) or different (switch trials). Naming
      latencies were longer on switch than on repeat trials, independent of the
      response language. Cue-locked ERPs showed an early posterior negativity for
      switch compared to repeat trials for L2 but not for L1, and a late anterior
      negativity for switch compared to repeat trials for both languages. The early
      switch-repeat effect might reflect disengaging from the nontarget native
      language, whereas the late switch-repeat effect reflects engaging in the target
      language. Implications for models of bilingual word production are discussed.

PMID- 19580394
TI  - Interactions between language and attention systems: early automatic lexical
      processing?
AB  - An ongoing debate is whether and to what extent access to cortical
      representations is automatic or dependent on attentional processes. To address
      this, we modulated the level of attention on auditory input and recorded ERPs
      elicited by syllables completing acoustically matched words and pseudowords.
      Under nonattend conditions, the word-elicited response (peaking at approximately
      120 msec) was larger than that to pseudowords, confirming early activation of
      lexical memory traces. However, when attention was directed toward the auditory
      input, such word-pseudoword difference disappeared. Whereas responses to words
      seemed unchanged by attentional variation, early pseudoword responses were
      modulated significantly by attention. Later on, attention modulated a positive
      deflection at approximately 230 msec and a second negativity at approximately 370
      msec for all stimuli. The data indicate that the earliest stages of word
      processing are not affected by attentional demands and may thus possess certain
      automaticity, with attention effects on lexical processing accumulating after 150
      200 msec. We explain this by robustness of preexisting memory networks for words
      whose strong internal connections guarantee rapid full-scale activation
      irrespective of the attentional resources available. Conversely, the processing
      of pseudowords, which do not have such stimulus-specific cortical
      representations, appears to be strongly modulated by the availability of
      attentional resources, even at its earliest stages. Topography analysis and
      source reconstruction indicated that left peri-sylvian cortices mediate attention
      effects on memory trace activation.

PMID- 19580396
TI  - 'The Little Purple Book': BSI glossary of regenerative medicine. Foreword.

PMID- 19580397
TI  - Cellular transplants, 20 years later: the pharma initiative.

PMID- 19580400
TI  - Interview: stemming vision loss with stem cells: seeing is believing.
AB  - Professor Coffey joined the faculty at the University of Oxford in 1987 on
      completing his doctoral work. In 1989, he was awarded a personal Royal Society
      Research Fellowship, at the same time moving to the University of Sheffield to
      establish a new laboratory for retinal transplantation. After 14 years at the
      University of Sheffield, Prof. Coffey was appointed Professor in the newly built
      Henry Wellcome building for translational eye research at the Institute of
      Ophthalmology in London. Prof. Coffey has many years experience in cellular
      therapies as applied to retinal transplantation and was recently the principal
      author and co-author of two landmark papers demonstrating that grafting human
      cells could prevent visual loss. As Professor and head of Ocular Biology and
      Therapeutics, Prof. Coffey has established the London Project to Cure Blindness.
      This project aims to deliver a stem cell therapy for age-related macular
      degeneration by 2011.

PMID- 19580395
TI  - Mitochondrial regulation of cell survival and death during low-oxygen conditions.
AB  - Mitochondria can initiate cell death or activate genes that promote cell survival
      in response to low oxygen. The BCL-2 family of proteins regulate cell death in
      response to anoxia (0-0.5% O2). By contrast, under hypoxia (0.5-3% O2),
      mitochondrial oxidative stress activates hypoxia-inducible factors (HIFs) to
      promote cell survival. In this review, we discuss how mitochondria, BCL-2
      proteins, and HIFs are crucial for cellular responses to low oxygen.

PMID- 19580403
TI  - Effect of oxygen concentration, culture format and donor variability on in vitro
      chondrogenesis of human adipose tissue-derived stem cells.
AB  - BACKGROUND: The chondrogenic differentiation potential of the easily accessible
      adipose tissue-derived stem cells (ASCs) is of particular interest within the
      field of tissue engineering for treating cartilage defects. However, no consensus
      has been reached as to which oxygen tension is more beneficial for the
      differentiation process. MATERIALS & METHODS: In this investigation, the impact
      of available oxygen was investigated to identify optimal conditions for human ASC
      chondrogenesis in vitro. Four physiologically relevant oxygen concentrations of
      15, 10, 5 and 1% were compared with ambient air condition, and the ASCs
      originating from six unrelated donors were subjected to chondrogenic induction in
      high-density pellet cultures. RESULTS: The qualitative and quantitative
      assessment of accumulated extracellular matrix and the gene-expression analysis
      revealed marked interindividual differences, nevertheless the chondrogenic
      process was optimally supported in high-density pellet setup at ambient or 15%
      oxygen concentrations, irrespective of the origin of cells. The histochemical
      analysis based on alcian blue staining demonstrated that the differentiation took
      place in a gradient-like fashion, displaying highest levels in restricted
      regions, most often adjacent to the periphery. The two lowest hypoxic conditions,
      at 5 and 1% oxygen, seemed to have an inhibitory effect. CONCLUSION: The
      micropellet cultures at ambient or 15% oxygen concentration provided the most
      suitable environment for inducing chondrogenesis in ASCs. Furthermore, in light
      of the fact that the induction appeared in a zone-dependent manner, this format
      lends itself as a suitable model for further analysis of the relationship between
      chondrogenic differentiation and the gradient of nutrients.

PMID- 19580402
TI  - Bone marrow-derived mesenchymal stem cells in fibrin augment angiogenesis in the
      chronically infarcted myocardium.
AB  - AIMS: Current efforts to treat myocardial infarction include the delivery of
      cells and matrix scaffolds. Bone marrow-derived mesenchymal stem cells (BM-MSCs)
      are multipotent stem cells that secrete angiogenic growth factors, and fibrin has
      been shown to be a biomaterial that provides structural support to cells and
      tissues. The objective of this study was to characterize the attachment and
      viability of BM-MSCs in fibrin in vitro, and then to assess the efficacy of
      treatment with BM-MSCs in fibrin for promoting neovascularization in the
      chronically infarcted myocardium. MATERIALS & METHODS: BM-MSCs were cultured in
      fibrin and assessed for cell attachment and viability by using immunofluorescence
      staining for actin filaments and Live/Dead((R)) viability assays, respectively.
      To determine the efficacy of BM-MSCs in fibrin in vivo, chronically infarcted rat
      hearts were treated with either cells, cells in fibrin, fibrin or saline (n = 9).
      After 5 weeks, the infarct scar tissues were assessed for neovascularization.
      RESULTS: BM-MSCs exhibited robust cell attachment and viability when cultured in
      fibrin in vitro. Furthermore, when injected together into the infarcted tissue,
      BM-MSCs in fibrin could enhance neovasculature formation by increasing capillary
      density, in comparison to treatment by cells or fibrin separately. Concomitant to
      significant improvement in capillary density was an increase in the levels of
      VEGF in the infarct scar. CONCLUSION: This study demonstrates the angiogenic
      potential of the combined delivery of BM-MSCs and fibrin, and highlights the
      advantage of stem cell-matrix approaches for myocardial repair.

PMID- 19580404
TI  - Industry perceptions of barriers to commercialization of regenerative medicine
      products in the UK.
AB  - AIMS: Regenerative medicine is an emerging field with the potential to provide
      widespread improvement in healthcare and patient wellbeing via the delivery of
      therapies that can restore, regenerate or repair damaged tissue. As an industry,
      it could significantly contribute to economic growth if products are successfully
      commercialized. However, to date, relatively few products have reached the market
      owing to a variety of barriers, including a lack of funding and regulatory
      hurdles. The present study analyzes industry perceptions of the barriers to
      commercialization that currently impede the success of the regenerative medicine
      industry in the UK. MATERIALS & METHODS: The analysis is based on 20 interviews
      with leading industrialists in the field. RESULTS: The study revealed that
      scientific research in regenerative medicine is thriving in the UK.
      Unfortunately, lack of access to capital, regulatory hurdles, lack of clinical
      evidence leading to problems with reimbursement, as well as the culture of the
      NHS do not provide a good environment for the commercialization of regenerative
      medicine products. CONCLUSION: Policy interventions, including increased
      translational government funding, a change in NHS and NICE organization and
      policies, and regulatory clarity, would likely improve the general outcomes for
      the regenerative medicine industry in the UK.

PMID- 19580406
TI  - Engineering tissue alternatives to animals: applying tissue engineering to basic
      research and safety testing.
AB  - The focus for the rapid progress in the field of tissue engineering has been the
      clinical potential of the technology to repair, replace, maintain or enhance the
      function of a particular tissue or organ. However, tissue engineering has much
      wider applicability in basic research and safety testing, which is often not
      recognized owing to the clinical focus of tissue engineers. Using examples from a
      recent National Centre for the Replacement, Refinement and Reduction of Animals
      in Research/Biotechnology and Biological Sciences Research Council symposium,
      which brought together tissue engineers and scientists from other research
      communities, this review highlights the potential of tissue engineering to
      provide scientifically robust alternatives to animals to address basic research
      questions and improve drug and chemical development in the pharmaceutical and
      chemical industries.

PMID- 19580408
TI  - Commercial development of cell-based therapeutics: strategic considerations along
      the drug to tissue spectrum.
AB  - In cell-based therapy, the process defines the product and the biological
      interaction between implant and host determines the outcome. Developing the
      optimum combination of process, product and a clinically relevant effect has been
      a challenge, leaving many potential therapies stalled in early clinical studies.
      This special report discusses pivotal factors in the development of cell-based
      technologies, irrespective of where they fit on the spectrum from cell-based drug
      to tissue construct, and how we can ensure delivery of an effective product to
      the clinic and the marketplace. Epidermal cell-based therapies serve as an
      historical lesson.

PMID- 19580405
TI  - Role of bioinspired polymers in determination of pluripotent stem cell fate.
AB  - Human pluripotent stem cells, including embryonic and induced pluripotent stem
      cells, hold enormous potential for the treatment of many diseases, owing to their
      ability to generate cell types useful for therapeutic applications. Currently,
      many stem cell culture propagation and differentiation systems incorporate animal
      derived components for promoting self-renewal and differentiation. However, use
      of these components is labor intensive, carries the risk of xenogeneic
      contamination and yields compromised experimental results that are difficult to
      duplicate. From a biomaterials perspective, the generation of an animal- and cell
      free biomimetic microenvironment that provides the appropriate physical and
      chemical cues for stem cell self-renewal or differentiation into specialized cell
      types would be ideal. This review presents the use of natural and synthetic
      polymers that support propagation and differentiation of stem cells, in an
      attempt to obtain a clear understanding of the factors responsible for the
      determination of stem cell fate.

PMID- 19580407
TI  - Emerging concepts in engineering extracellular matrix variants for directing cell
      phenotype.
AB  - Directing specific, complex cell behaviors, such as differentiation, in response
      to biomaterials for regenerative medicine applications is, at present, a mostly
      unrealized goal. To date, current technological advances have been inspired by
      the reductionist point of view, focused on developing simple and merely adequate
      environments that facilitate simple cellular adhesion. However, even if
      extracellular matrix (ECM)-derived peptides, such as Arg-Gly-Asp (RGD), have
      largely demonstrated their utility in supporting cell adhesion, their lack of
      biological specificity is simply not optimal for controlling more integrated
      processes, such as cell differentiation. These more complex cellular processes
      require specific integrin-signaling scaffolds and presumably synergistic integrin
      and growth factor-receptor signaling. This article will introduce some current
      efforts to engineer ECM variants that incorporate additional levels of complexity
      for directing greater integrin specificity and synergistic ECM growth factor
      signaling toward directing cell phenotype.

PMID- 19580409
TI  - In vivo tissue engineering of heart valves: evolution of a novel concept.
AB  - Current tissue-engineering principles of heart valves include tissue- or stem
      cell-derived cells with subsequent in vitro incubation on various scaffolds prior
      to implantation. Limitations of this approach include a long in vitro culture, an
      accompanied risk of infection and sophisticated, cost-intensive infrastructures.
      An 'off-the-shelf' heart valve with in vivo endothelialization and tissue
      regeneration potential would overcome these limitations. Additionally, the
      development of a heart valve with growth potential would be a huge improvement
      for pediatric patients. This article discusses different starter matrices, homing
      and immobilization strategies of host cells and masking approaches of
      inflammatory structures for in vivo surface and tissue engineering of heart
      valves. Novel concepts will be presented based on highly specific DNA-aptamers
      immobilized on the heart valve surface as capture molecules for endothelial
      progenitor cells circulating in the bloodstream.

PMID- 19580410
TI  - New glossary of terms used in regenerative medicine: standardization continues to
      emerge as regenerative medicine matures.
AB  - Regenerative medicine is an evolving, cross-disciplinary, international field
      that, as a result, uses terms that are either not widely understood, or may have
      a number of different meanings. Many stakeholders have identified this lack of
      clarity as a potential barrier to effective communication within the field. To
      address this, BSI British Standards, supported by the UK Department for
      Innovation, Universities and Skills (DIUS), was commissioned to develop guidance
      on the definitions of terms used within regenerative medicine. The resulting
      document aims to provide clear consensus terminology to improve communication and
      facilitate a common understanding for a broad range of potential users.

PMID- 19580412
TI  - Sustained virological response after early antiviral treatment of acute hepatitis
      C virus and HIV coinfection.
AB  - BACKGROUND: Limited data exist describing the clinical outcome and immunological
      response primed during simultaneously acquired acute hepatitis C virus (HCV) and
      human immunodeficiency virus (HIV) coinfection. We present detailed clinical and
      immunological analysis of 3 individuals after concomitant infection with acute
      HCV and primary HIV. METHODS: In addition to longitudinal clinical parameters,
      virus-specific T cell responses were assessed using Elispot, standard
      proliferative (carboxyfluorescein diacetate succinimidyl ester), and in vitro
      CD4(+) T cell assays. RESULTS: In all patients, anti-HCV treatment was started
      with pegylated interferon-alpha, and antiretroviral therapy was coadministered
      early during primary infection. HCV viremia was cleared under therapy with
      pegylated interferon-alpha in all 3 cases. In 2 patients, HIV replication was
      contained even after antiretroviral therapy had been interrupted, which was
      associated with strong HIV-specific CD8(+) and CD4(+) T cell responses. In these
      2 patients, multispecific HCV CD4(+) T cell responses could also be detected. No
      HCV-specific CD4(+) T cell responses were detected in the third patient, who also
      had the lowest nadir CD4(+) cell count during primary HIV infection (<200
      cells/microL). CONCLUSIONS: Anti-HIV and -HCV therapy should be considered early
      in cases of concomitant acute HCV and HIV coinfection, because successful therapy
      of HCV viremia seems possible even during primary HIV infection. HCV-specific T
      cell immunity is generated during primary HIV infection and can be preserved by
      HCV treatment. However, the optimal treatment algorithm needs to be established
      in prospective, randomized trials.

PMID- 19580413
TI  - A possible cluster of sexually transmitted Entamoeba histolytica: genetic
      analysis of a highly virulent strain.
AB  - BACKGROUND: Transmission of Entamoeba histolytica generally occurs by fecal
      excretion of cysts followed by oral ingestion of contaminated food or water.
      However, fecal-oral transmission may occur within households and long-term care
      institutions, and sexual transmission occurs among men who have sex with men.
      Epidemiologically linked clusters of E. histolytica infection are rare in
      industrialized countries. We report such a sexually linked cluster in Canada.
      METHODS: An index case involving a young female with an amebic liver abscess led
      to an epidemiological investigation of sexual contacts. Anti-amebic serological
      analysis, stool specimen examinations, and abdominal ultrasounds were done for
      the contacts. Enzyme-linked immunosorbent assay was done for stool antigen
      specific to E. histolytica. Genotyping and phylogenetic analysis was performed on
      1 stool isolate. RESULTS: By tracing sexual contacts related to the index case,
      we uncovered a cluster of 7 cases of amebiasis (3 with liver abscesses). Oral
      anal sex was common in the group; the 5 female individuals were bisexual (4) or
      homosexual (1). The outbreak strain was genotyped, and cluster analysis indicated
      that this virulent strain differed substantially from asymptomatic or diarrheal
      E. histolytica isolates. CONCLUSIONS: E. histolytica can be transmitted by
      heterosexual activity as well as male and female homosexual activity. Patients
      with amebiasis should be counselled about possible sexual transmission.

PMID- 19580414
TI  - Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for
      universal intrapartum group B streptococcus screening.
AB  - BACKGROUND: Intrapartum antibiotic prophylaxis is currently given to mothers who
      test positive for group B streptococcus (GBS) by antenatal culture-based
      screening, with a risk-based approach for cases with an unknown GBS status. A
      rapid real-time polymerase chain reaction (PCR) assay for the detection of GBS
      became available recently, making intrapartum screening possible. We aimed to
      assess its diagnostic accuracy and to compare it with antenatal screening.
      METHODS: We conducted a prospective study in a French hospital. All pregnant
      women giving birth at the maternity ward were considered for inclusion, except
      those with planned cesarean delivery, with delivery at <35 weeks gestation, and
      who received antibiotic therapy before admission. We performed GBS culture (the
      reference standard) and a molecular GBS test (Xpert GBS; Cepheid) on intrapartum
      specimens. Decisions about intrapartum antibiotic prophylaxis were based on the
      current GBS screening by culture at 35-37 weeks gestation. RESULTS: We
      prospectively enrolled 968 pregnant women from April 2007 through March 2008. The
      overall molecular GBS test yield was 89.2%. Among the 863 women with available
      results, the molecular GBS test had a sensitivity of 98.5%, specificity of 99.6%,
      positive predictive value of 97.8%, and negative predictive value of 99.7%. The
      positive predictive value of antenatal culture for identifying colonization
      status at delivery was low (58.3%), whereas the negative predictive value was
      imperfect (92.1%). CONCLUSIONS: This real-time PCR assay is a highly accurate
      test to identify intrapartum GBS carriers at point of care. This new tool could
      enhance the exact identification of candidates for intrapartum antibiotic
      prophylaxis, including women with preterm rupture of membranes or preterm labor.

PMID- 19580415
TI  - Nosocomial transmission of invasive group a streptococcus from patient to health
      care worker.
AB  - BACKGROUND: Nosocomial transmission of group A streptococcus (GAS) has been well
      described. Instances resulting in fulminant disease among health care workers
      have not been described. Contact and droplet precautions have been advised to
      minimize the risk of nosocomial transmission. We aimed to determine whether a
      case of invasive GAS pneumonia and streptococcal toxic shock syndrome in a
      respiratory therapist was acquired as a result of caring for a patient with GAS
      necrotizing fasciitis. Contacts of these patients were screened to determine if
      they were the reservoir of the GAS. Genetic testing to confirm clonal
      transmission was conducted. METHODS: Contacts of the patients with GAS infection
      were screened using questionnaires and testing of pharyngeal specimens. Specimens
      from patients and carriers of GAS who were identified during screening were
      subjected to pulsed-field gel electrophoresis and emm gene typing. RESULTS: We
      identified 705 contacts of the 2 patients; all contacts had oropharyngeal
      specimens collected for culture. Only the index patient and the respiratory
      therapist yielded identical pulse-field gel electrophoresis GAS isolates, with
      clonality indicated by emm typing. CONCLUSIONS: Nosocomial transmission of GAS
      from a patient to a health care worker who developed streptococcal toxic shock
      syndrome may have occurred after the index patient had received 48 h of
      antibiotic therapy and despite placement in contact isolation. Isolation
      guidelines for patients with severe GAS infection may need to be reviewed.

PMID- 19580416
TI  - Antibiotic dosing in slow extended daily dialysis.
AB  - Slow extended daily dialysis (SLEDD) is the newest form of dialysis that is being
      used increasingly to replace continuous venovenous hemodialysis (CVVHD) for
      critically ill patients; it is less expensive to administer and has similar
      safety for patients who are prone to hemodynamic instability. Unfortunately,
      there are limited data regarding the appropriate dosing of antimicrobial agents
      for patients undergoing SLEDD. Furthermore, many nonnephrologists are not
      familiar with the differences between SLEDD, other continuous renal replacement
      therapies--for example, CVVHD--and routine hemodialysis. Thus, there is potential
      for inaccurate and, at worst, inadequate dosing of critical antimicrobial agents
      for this patient population. We review the available pharmacokinetic data on
      SLEDD and give preliminary recommendations for how to approach dosing in this
      situation.

PMID- 19580417
TI  - Haemophilus influenzae serotype b vaccine failure: what is the significance of
      antibody levels?

PMID- 19580418
TI  - Long-term immunological follow-up of children with haemophilus influenzae
      serotype b vaccine failure in the United Kingdom.
AB  - BACKGROUND: It is not known how long children with Haemophilus influenzae
      serotype b (Hib) vaccine failure retain protective Hib antibody concentrations
      after infection. The objective of this study was to determine Hib antibody
      concentrations in children several years after infection and to identify risk
      factors for low antibody concentrations. METHODS: The families of children from
      the United Kingdom who developed invasive Hib disease after prior immunization
      with Hib conjugate vaccine (i.e., Hib vaccine failure) from October 1992 through
      December 2005 were asked to complete a questionnaire. A blood sample was also
      obtained from each child. RESULTS: Of 323 families approached, 260 (80.5%)
      returned a completed questionnaire, and 175 (54.2%) children provided a blood
      sample. The median age at follow-up was 8.4 years (interquartile range [IQR], 6.2
      15.4 years), and the median duration of follow-up was 4.1 years (IQR, 3.5-9.7
      years). Twenty-seven children (16.1%) had been born prematurely and/or had an
      underlying medical condition, and 18 (10.8%) had immunoglobulin deficiency. The
      median Hib antibody concentration was 0.70 microg/mL (IQR, 0.22-5.8 microg/mL).
      Overall, 95 children (56.9%) had antibody concentrations <1.0 microg/mL, and 27
      (16.2%) had antibody concentrations <0.15 microg/mL. All 3 children with Down
      syndrome and 10 (42%) of 24 children aged <5 years at follow-up had Hib antibody
      concentrations <0.15 microg/mL. An antibody concentration <0.15 microg/mL was
      independently associated with underlying conditions, young age at onset of Hib
      disease, and shorter time from Hib disease to follow-up. CONCLUSIONS: More than
      one-half of the children with Hib vaccine failure had antibody concentrations
      below those considered to confer long-term protection, which suggests that these
      children might be at further risk of invasive Hib disease and would benefit from
      another dose of Hib vaccine.

PMID- 19580420
TI  - A novel cylinder-type poly(L-lactic acid)-collagen hybrid sponge for cartilage
      tissue engineering.
AB  - The development of porous scaffolds having both high porosity and strong
      mechanical strength for tissue engineering and regenerative medicine has been
      quite challenging. A novel hybrid poly(L-lactic acid) (PLLA)-collagen hybrid
      sponge was developed by enclosing collagen sponge in a cup-shaped PLLA sponge to
      meet the necessary requirements. Collagen sponge was formed in the center of the
      PLLA sponge cup, and collagen microsponges were formed in the pores of the PLLA
      sponge cup. The PLLA-collagen hybrid sponge showed higher mechanical strength
      than did those of the PLLA sponge cup and collagen sponge. The porosity of the
      PLLA-collagen hybrid sponge was greater than that of the PLLA sponge cup. The cup
      shaped PLLA sponge skeleton provided the hybrid sponge with high mechanical
      strength and protected against cell leakage during cell seeding, while the
      central collagen sponge contributed to high porosity, and facilitated cell
      adhesion and distribution in the hybrid sponge. Cartilaginous tissue was
      successfully regenerated when chondrocytes were cultured in the hybrid sponge.
      This method of hybridization will provide a new technique for the preparation of
      functional porous scaffolds for tissue engineering.

PMID- 19580419
TI  - Temporospatial expression and cellular localization of oligodendrocyte myelin
      glycoprotein (OMgp) after traumatic spinal cord injury in adult rats.
AB  - Traumatic spinal cord injury (SCI) leads to permanent neurological deficits,
      which, in part, is due to the inability of mature axons to regenerate in the
      mammalian central nervous system (CNS). The oligodendrocyte myelin glycoprotein
      (OMgp) is one of the myelin-associated inhibitors of neurite outgrowth in the
      CNS. To date, limited information is available concerning its expression
      following SCI, possibly due to the lack of a reliable antibody against it. Here
      we report the generation of a highly specific OMgp polyclonal antibody from the
      rabbit. Using this antibody, we found that OMgp was almost exclusively expressed
      in the CNS. Following a moderately contusive SCI using a New York University
      impactor (10 g rod dropped from a height of 12.5 mm), both OMgp mRNA and protein
      levels were elevated at 1 and 7 days post-SCI, respectively, and peaked at 28
      days compared to those of the sham-operated controls. Spatially, OMgp was
      expressed throughout the entire rostrocaudal extension of a 10 mm long spinal
      segment with the highest expression seen at the injury epicenter. OMgp was
      exclusively localized in neurons and oligodendrocytes in the normal and sham
      operated controls with an increased expression found in these cells following
      SCI. OMgp was not expressed in astrocytes or microglia in all groups. Thus, our
      study has provided evidence for temporospatial expression and cellular
      localization of OMgp following SCI and suggested that this molecule may
      contribute to the overall inhibition of axonal regeneration.

PMID- 19580421
TI  - Pore characteristics of chitosan scaffolds studied by electrochemical impedance
      spectroscopy.
AB  - In this study, a novel approach, electrochemical impedance spectroscopy (EIS),
      was used to examine the pore characteristics of chitosan scaffolds under aqueous
      conditions. The EIS was run with a constant current of 0.1 mA with the frequency
      sweep of 10(6) to 10(-4) Hz. The resulting complex impedance measurement was then
      used to calculate porosity, which was determined to be 71%. Scanning electron
      microscopy (SEM) and mercury intrusion porosimetry (MIP), two commonly used
      methods for scaffold characterization, were used to independently evaluate the
      pore characteristics and compare with that of EIS. The SEM and MIP were performed
      and analyzed under standard conditions. The pore diameter values found by SEM and
      MIP are 107 mum and 82 mum, respectively, indicating that both the image-based
      (SEM) and pressure-based (MIP) analyses provide similar results. The porosity of
      73% calculated by MIP is comparable to that of EIS. From these results, it can be
      suggested that EIS, a relatively nondestructive test, is able to obtain
      comparable data on pore characteristics, as compared to SEM and MIP. The
      advantage of the EIS as an nondestructive test is that it can be performed under
      physiologically relevant conditions, whereas SEM and MIP require dry samples and
      vacuum conditions for measurement. These benefits make EIS a viable option for
      the characterization and long-term observation of tissue-engineered scaffolds.

PMID- 19580422
TI  - Nondestructive evaluation of cell numbers in bone marrow stromal cell/beta
      tricalcium phosphate composites using ultrasound.
AB  - Composites of bone marrow stromal cells (BMSCs)/beta-tricalcium phosphate (beta
      TCP) have been increasingly used as bone substitutes and studied as a bone graft
      model for bone tissue engineering. The number of seeded cells in the composites
      is a crucial factor for achieving successful bone tissue regeneration. In this
      study, we showed that the actual number of cells in BMSC/beta-TCP composites 24 h
      after seeding at densities of 1.0 x 10(6), 1.5 x 10(6), 2.0 x 10(6), and 1.0 x
      10(7) cells/mL was 2.8 +/- 1.5 x 10(5), 3.4 +/- 2.3 x 10(5), 3.7 +/- 1.0 x 10(5),
      and 3.7 +/- 1.8 x 10(5), respectively, indicating that even when one regular cell
      seeding concentration was applied to the beta-TCP, the actual number of cells in
      the individual BMSC/beta-TCP composites varied considerably. In clinical setting,
      it is important to choose composites containing an appropriate number of cells
      before implanting them to patients. In an attempt to searching for the practical
      tools that can nondestructively evaluate the actual number of cells in beta-TCP
      after cell seeding, we looked into ultrasound system and developed a
      nondestructive and quantitative ultrasound device. We successfully demonstrated
      for the first time that ultrasound amplitude effectively responded to the
      quantity of BMSC/beta-TCP composites after 24-h cell seeding, and was well
      correlated to the actual number of cells contained (r = 0.903). Using this
      ultrasound device, orthopedic surgeons can choose composites that contain
      favorable number of cells before implantation. Our device could be a valuable,
      convenient, and nondestructive tool for future bone tissue engineering.

PMID- 19580423
TI  - Towards molecular diagnostics of invasive fungal infections.

PMID- 19580424
TI  - Gene promoter analysis in molecular diagnostics: do or don't?

PMID- 19580426
TI  - Updates in cancer research: insights from the AACR 100th Annual Meeting.
AB  - Pivotal presentations from the 100th Annual Meeting 2009 of the American
      Association for Cancer Research (AACR) are reviewed in this article, along with
      discussion of scientific findings and their impact on clinical practices and
      ongoing clinical trials. Among these presentations, the report on predictive
      biomarkers for targeted therapies may lead to the possibility of selection of the
      right drug for the right patient. The results of cancer genomic researches has
      started to yield surprising insights into the pathogenesis of a range of
      different cancers, with analyses of somatic copy number alterations, genomic
      rearrangements and sequence mutations. Cancer stem cells have again been
      confirmed to play an important role in therapeutic resistance, promoting
      angiogenesis and metastasis. A diversity of viewpoints from different cancer
      types regarding the current understanding of cancer stem cell biology was
      introduced. MicroRNA alterations were also investigated and findings of recent
      studies were summarized. Apart from cancer cells, researchers have begun to
      examine the communication between the tumor cells and its surroundings. Novel
      findings on tumor microenvironment and inflammation were introduced. The latest
      developments of nanotechnology and biomarker discoveries were also presented. In
      addition, there were clinical trials supporting the use of new targeted
      therapies, while other researchers focused on cancer prevention using existing
      agents and approaches. These and other important presentations from the AACR
      Annual Meeting 2009 are discussed in this article, which intends to provide
      updates on the cancer research presented in the most important cancer research
      meeting in the world.

PMID- 19580427
TI  - MammaPrint 70-gene signature: another milestone in personalized medical care for
      breast cancer patients.
AB  - The MammaPrint assay (Agendia BV, The Netherlands) is the first fully
      commercialized microarray-based multigene assay designed to individualize
      treatment for patients with breast cancer. MammaPrint, the first assay to be
      cleared at the 510(k) level by the US FDA's new in vitro diagnostic multivariate
      index assay classification, is offered as a prognostic test for women under the
      age of 61 years with either estrogen receptor-positive or -negative, lymph node
      negative breast cancer. Unlike the Oncotype DX assay (Genomic Health, CA, USA),
      this test requires freshly prepared tissues collected into an RNA preservative
      solution. The 70 genes that comprise the MammaPrint assay are focused primarily
      on proliferation with additional genes associated with invasion, metastasis,
      stromal integrity and angiogenesis. The Microarray In Node-negative Disease may
      Avoid Chemotherapy (MINDACT) trial, sponsored by the European Organization for
      Research and Treatment of Cancer, involves the assessment of patients in the
      adjuvant treatment setting by the standard clinicopathologic prognostic factors
      included on Adjuvant! Online and by the 70-gene MammaPrint assay. The following
      article will consider the basic biology, technology, ease of clinical use, level
      of clinical validation and potential clinical utility of this test.

PMID- 19580429
TI  - Molecular markers of breast axillary lymph node metastasis.
AB  - In breast cancer, axillary lymph node status is one of the most important
      prognostic variables and a crucial component to the staging system. Several
      clinico-histopathological parameters are considered to be strong predictors of
      metastasis; however, they fail to accurately classify breast tumors according to
      their clinical behavior and to predict which patients will have disease
      recurrence. Methods based on genome-wide microarray analyses have been used to
      identify molecular markers with respect to the development of axillary lymph node
      metastasis. Most of these markers can be detected in the primary tumors, which
      can potentially lead to the ability to identify patients at the time of diagnosis
      who are at high risk for lymph node metastasis, allowing for early intervention
      and more suitable adjuvant treatments.

PMID- 19580428
TI  - MMTV mouse models and the diagnostic values of MMTV-like sequences in human
      breast cancer.
AB  - Mouse mammary tumor virus (MMTV) long terminal repeat (LTR)-driven transgenic
      mice are excellent models for breast cancer as they allow for the targeted
      expression of various oncogenes and growth factors in neoplastic transformation
      of mammary glands. Numerous MMTV-LTR-driven transgenic mouse models of breast
      cancer have been created in the past three decades, including MMTV-neu/ErbB2,
      cyclin D1, cyclin E, Ras, Myc, int-1 and c-rel. These transgenic mice develop
      mammary tumors with different latency, histology and invasiveness, reflecting the
      oncogenic pathways activated by the transgene. Recently, homologous sequences of
      the env gene of MMTV have been identified in approximately 40% of human breast
      cancers, but not in normal breast or other types of cancers, suggesting possible
      involvement of mammary tumor virus in human breast carcinogenesis. Accumulating
      evidence demonstrates the association of MMTV provirus with progesterone
      receptor, p53 mutations and advanced-stage breast cancer. Thus, the detection of
      MMTV-like sequences may have diagnostic value to predict the clinical outcome of
      breast cancer patients.

PMID- 19580431
TI  - Mechanisms of resistance to ionizing radiation in rectal cancer.
AB  - While patients with breast cancers are not subjected to the adverse side effects
      of tamoxifen or trastuzumab if their tumors are negative for estrogen,
      progesterone or Her-2/Neu, neoadjuvant ionizing radiation with concurrent
      chemotherapeutic agents is administered almost universally to patients with stage
      II/III rectal cancers. There is, however, a tremendously wide range of response
      to this preoperative modality from complete pathological response to continuous
      tumor growth in patients receiving the same form of treatment. The specific
      phenotype of the tumor plays a major role in rendering tumor cells survival
      advantage to the cytotoxic effects of chemoradiation. Pathways such as
      proliferation, cell cycle, apoptosis and hypoxia have been investigated under a
      variety of conditions in preirradiated tissues and postirradiated tumors. This
      article reviews the current evidence available to identify a molecular profile
      predictive of the best response to ionizing radiation.

PMID- 19580432
TI  - Molecular diagnosis of myeloproliferative neoplasms.
AB  - The molecular profiling of myeloproliferative neoplasms (MPNs) has introduced a
      paradigm shift in the process of diagnosis, prognostication, monitoring and
      treatment of these diseases. The discovery of the BCR-ABL fusion oncogene is an
      example of a remarkable bench-to-bedside story. It has provided a comprehensive
      explanation of the pathogenesis of chronic myelogenous leukemia, and has resulted
      in the development of excellent treatment strategies. It has led to the use of
      advanced diagnostic techniques, such as fluorescence in situ hybridization and
      PCRs that allow for more effective means to monitor disease treatment, including
      the detection of minimal residual disease, early relapse and drug resistance.
      Unlike chronic myelogenous leukemia, the exact molecular pathways for the BCR-ABL
      negative MPNs have not been completely elucidated. The discoveries of the JAK2
      and the MPL mutations have set the ball rolling in trying to achieve this target.
      The JAK2 mutational screen has provided us with a relatively simple screening
      assay to establish clonality in the setting of MPNs. In patients with clonal
      eosinophilic disorders and mast cell disease, the use of molecular diagnostics to
      identify novel mutations and gene rearrangements, has resulted in superior
      diagnostic and therapeutic strategies.

PMID- 19580433
TI  - Influenza genome analysis using pyrosequencing method: current applications for a
      moving target.
AB  - Pyrosequencing is a high-throughput non-gel-based DNA sequencing method that was
      introduced in the late 1990s. It employs a DNA sequencing-by-synthesis approach
      based on real-time measurement of pyrophosphate released from incorporation of
      dNTPs. A cascade of enzymatic reactions proportionally converts the pyrophosphate
      to a light signal recorded in a form of peaks, known as pyrograms. Routinely, a
      45-60-nucleotide sequence is obtained per reaction. Recent improvements
      introduced in the assay chemistry have extended the read to approximately 100
      nucleotides. Since its advent, pyrosequencing has been applied in the fields of
      microbiology, molecular biology and pharmacogenomics. The pyrosequencing approach
      was first applied to analysis of influenza genome in 2005, when it played a
      critical role in the timely detection of an unprecedented rise in resistance to
      the adamantane class of anti-influenza drugs. More recently, pyrosequencing was
      successfully applied for monitoring the emergence and spread of influenza A
      (H1N1) virus resistance to oseltamivir, a newer anti-influenza drug. The present
      report summarizes known applications of the pyrosequencing approach for influenza
      genome analysis with an emphasis on drug-resistance detection.

PMID- 19580430
TI  - Current molecular diagnostics of breast cancer and the potential incorporation of
      microRNA.
AB  - Although comprehensive molecular diagnostics and personalized medicine have
      sparked excitement among researchers and clinicians, they have yet to be fully
      incorporated into today's standard of care. This is despite the discovery of
      disease-related oncogenes, tumor-suppressor genes and protein biomarkers, as well
      as other biological anomalies related to cancer. Each year, new tests are
      released that could potentially supplement or surpass standard methods of
      diagnosis, including serum, protein and gene expression analyses. All of these
      novel approaches have shown great promise, but initial enthusiasm has diminished
      as difficulties in reproducibility, expense, standardization and proof of
      significance beyond current protocols have emerged. This review will focus on
      current and novel molecular diagnostic tools applied to breast cancer with
      special attention to the exciting new field of microRNA analysis.

PMID- 19580434
TI  - Gold nanoparticles for molecular diagnostics.
AB  - Gold nanoparticles (AuNPs) exhibit a unique phenomenon, known as surface plasmon
      resonance, which is responsible for their large absorption and scattering cross
      sections, which are four to five orders of magnitude larger than those of
      conventional dyes. In addition, their optical properties can be controlled by
      varying their sizes, shapes and compositions. AuNPs can be easily synthesized and
      functionalized with different biomolecules including oligonucleotides. Numerous
      methods have been utilized for detecting AuNPs such as colorimetric, scanometric,
      fluorescence, surface-enhanced Raman scattering and electrochemical techniques.
      These unique aspects have permitted the development of novel AuNP-based assays
      for molecular diagnostics which promise increased sensitivity and specificity,
      multiplexing capability, and short turnaround times. AuNP-based colorimetric
      assays in particular show great potential in point-of-care testing assays. This
      review discusses properties of AuNPs and their utilization for the development of
      novel molecular assays.

PMID- 19580437
TI  - Hospital-wide methicillin-resistant Staphylococcus aureus control program: A 5
      year follow-up.
AB  - We investigated the influence of different interventions (active surveillance,
      contact isolation, monitoring, and rapid diagnostic testing) on the number of
      methicillin-resistant Staphylococcus aureus (MRSA) bacteremia cases. An
      interrupted time-series analysis was used. MRSA bacteremia cases were reduced by
      70% when all interventions were in place. We proved monitoring to be an essential
      component.

PMID- 19580436
TI  - A cluster of cases of nosocomial legionnaires disease linked to a contaminated
      hospital decorative water fountain.
AB  - BACKGROUND: Nosocomial outbreaks of Legionnaires disease have been linked to
      contaminated water in hospitals. Immunocompromised patients are particularly
      vulnerable and, when infected, have a high mortality rate. We report the
      investigation of a cluster of cases of nosocomial pneumonia attributable to
      Legionella pneumophila serogroup 1 that occurred among patients on our stem cell
      transplantation unit. METHODS: We conducted a record review to identify common
      points of potential exposure, followed by environmental and water sampling for
      Legionella species from those sources. We used an air sampler to in an attempt to
      detect aerosolized Legionella and pulsed-field gel electrophoresis to compare
      clinical and environmental isolates. RESULTS: The most likely sources identified
      were the water supply in the patients' rooms and a decorative fountain in the
      radiation oncology suite. Samples from the patients' rooms did not grow
      Legionella species. Cultures of the fountain, which had been restarted 4 months
      earlier after being shut off for 5 months, yielded L. pneumophila serogroup 1.
      The isolates from both patients and the fountain were identical by pulsed-field
      gel electrophoresis. Both patients developed pneumonia within 10 days of
      completing radiation therapy, and each reported having observed the fountain at
      close range. Both patients' infections were identified early and treated
      promptly, and both recovered. CONCLUSIONS: This cluster was caused by
      contamination of a decorative fountain despite its being equipped with a filter
      and ozone generator. Fountains are a potential source of nosocomial Legionnaires
      disease despite standard maintenance and sanitizing measures. In our opinion,
      fountains present unacceptable risk in hospitals serving immunocompromised
      patients.

PMID- 19580438
TI  - Staphylococcus aureus nasal colonization and colonization or infection at other
      body sites in patients on a burn trauma unit.
AB  - OBJECTIVE: To determine whether Staphylococcus aureus isolates from the nares of
      patients on a burn trauma unit were related to isolates colonizing or infecting
      other body sites. DESIGN: Active surveillance for S. aureus, a case-control
      study, and pulsed-field gel electrophoresis of S. aureus isolates. SETTING: A
      burn trauma unit of a Midwestern university teaching hospital. PATIENTS: Patients
      admitted from February 1, 2002, through March 30, 2007, who had S. aureus
      isolated either from a nasal culture and from another body site (case patients)
      or from a nasal culture alone (control subjects). RESULTS: Nineteen patients met
      the case patient definition and had paired isolates from the nares and an
      additional site available for typing. Of the 19 case patients, 8 had infections,
      7 of which were caused by methicillin-resistant S. aureus (5 USA100 strain and 2
      USA300 strain). A total length of stay of more than 3 weeks (odds ratio [OR],
      8.75 [95% confidence interval {CI}, 2.2-34.6]; P = .002), residence in a long
      term care facility (OR, 9.4 [95% CI, 2.1-42.5]; P = .004), and diabetes (OR, 3.2
      [95% CI, 1.0-10.0]; P = .05) were associated with the isolation of S. aureus from
      the nares and other sites. Seventeen case patients (89.5%) had closely related
      isolates obtained from culture of samples from the nares and from other sites.
      CONCLUSIONS: Prolonged length of stay, diabetes, or residing in a long-term care
      facility increased the risk of having S. aureus at sites other than the nares. S.
      aureus isolates from other body sites usually were closely related to nasal
      isolates. Most case patients had colonized or infected wounds that could be a
      source of S. aureus for other patients.

PMID- 19580439
TI  - Staphylococcus aureus: Not always right under your nose.

PMID- 19580440
TI  - To take or not to take genetic carrier tests: personal characteristics associated
      with taking recommended and nonrecommended tests.
AB  - AIMS: Genetic testing has become a routine part of prenatal care, the test being
      offered according to ethnic origin. However, not all clients take the offered
      tests while others take unnecessary tests. The present study aimed at examining
      the effects of risk perception, hypochondria, trait anxiety, and attitudes to
      genetic testing on the uptake of genetic carrier tests. METHODS: One hundred and
      six pregnant Israeli women completed a six-part questionnaire covering
      demographic details, hypochondria, trait anxiety, risk perception, attitudes, and
      the uptake of genetic carrier tests. The uptake of recommended and nonrecommended
      tests (according to origin) was analyzed separately. RESULTS: Women underwent
      many unnecessary tests. The uptake of recommended and nonrecommended tests is
      highly intercorrelated. Attitude was the only predictor for taking the
      recommended tests, but attitudes, trait anxiety, and hypochondria predicted the
      uptake of nonrecommended tests. Risk perception was not significantly related to
      the dependent variables. CONCLUSIONS: Attitudes toward genetic testing is an
      important factor in the decision to take genetic carrier tests. It is important
      to understand the different causal factors for taking recommended and
      nonrecommended tests.

PMID- 19580441
TI  - Genetic testing for inflammatory bowel disease: focus group analysis of patients
      and family members.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal
      illness with complex genetic underpinnings. Genetic testing for IBD, in
      particular, for high-risk alleles, is not currently used in clinical practice.
      Further, preferences and concerns of patients and their family members regarding
      a genetic test for this condition are not well studied. METHODS: Thirty IBD
      patients and eighteen unaffected first-degree family members or spouses listened
      to a general educational session about IBD and then participated in one of eight
      focus groups in order to identify themes of concern and interest regarding a
      genetic test for IBD. Participants also completed demographic, attitude, and
      knowledge surveys prior to the focus group sessions. Qualitative analysis of
      transcripts was performed, and simple comparative statistics of survey data were
      calculated. RESULTS: There were few differences between the responses of patients
      and unaffected family members. Participants were interested in undergoing genetic
      testing for IBD despite the fact that information at this time cannot be
      clinically applied in the diagnosis, prognosis, or treatment of the disease.
      Advantages of genetic testing commonly identified included benefit to themselves
      and family members through the possibility of earlier diagnosis and targeted
      therapies. Disadvantages commonly cited were discrimination by insurance
      companies and employers and concerns about protection of information. In general,
      participants were interested in receiving both pre- and posttest information from
      an informed gastroenterologist, which included a clear basis for testing and the
      implications of the results for themselves and for family members. CONCLUSIONS:
      The results of the first focus group assessment about genetic testing for IBD
      reveal themes that are similar in interests and concerns to other genetic
      diseases. These findings will aid in the construction of patient-centered models
      of genetic testing that emphasize patient education and interpretation of
      results.

PMID- 19580442
TI  - An Indian boy with nephropathic cystinosis: a case report and molecular analysis
      of CTNS mutation.
AB  - Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized
      by excessive accumulation of cystine within the lysosome. Cystinosis is caused by
      mutations in the lysosomal cystine transporter, cystinosin (CTNS). The CTNS gene
      consists of 12 exons and encodes for an integral lysosomal membrane protein with
      seven transmembrane domains. A majority of cystinotic patients are of European
      descents, and only a few cases have been reported from other ethnic groups. Here
      we report a case of nephropathic cystinosis in an Indian boy born to
      consanguineous parents. Major symptoms of the patient include weight loss,
      vomiting, dehydration, and cystine crystals in the cornea. Ichthyosis on the arms
      and legs is also observed. Sequencing analysis of all the CTNS exons revealed
      that the proband is homozygous for a 3-bp in-frame deletion in exon 10
      (c.809_811delCCT), resulting in the loss of a conserved p.Ser270del within the
      fifth transmembrane domain of CTNS. His parents are both heterozygous for the
      same mutation. This work represents the first molecular characterization of
      cystinotic patients from India. Interestingly, a p.Ser270del resulting from
      c.809_811delCCT in CTNS had been identified in a European patient. Therefore, it
      appears that this mutation arose independently in the two different continents.

PMID- 19580444
TI  - Antimicrobial resistance profiles and mechanisms of resistance in Campylobacter
      jejuni isolates from pets.
AB  - The presence of antimicrobial resistance in 51 Campylobacter jejuni isolates
      obtained from cats and dogs was determined by E-testing. Resistance to nalidixic
      acid (37.3% of isolates), ciprofloxacin (19.6%), tetracycline (13.7%), ampicillin
      (13.7%), erythromycin (11.8%), and chloramphenicol (5.9%) was detected.
      Resistance to two antimicrobials or more was present in 31.4% of isolates, and
      one isolate was resistant to all six antimicrobials. Of the isolates with
      ciprofloxacin and/or nalidixic acid resistance, 54.5% had the gyrA substitution
      Thr-86-Ile on sequencing. The tet o gene was detected in 75.0% isolates with high
      level resistance to tetracycline. With the observed antimicrobial resistance in
      C. jejuni isolates from pets in this study, and the detection of identical
      mechanisms for quinolone and tetracycline resistance in pets and humans, pets
      should be considered a potential source of (multi)resistant C. jejuni infections
      in humans.

PMID- 19580443
TI  - Intestinal epithelial cells in vitro.
AB  - Recent advances in the biology of stem cells has resulted in significant interest
      in the development of normal epithelial cell lines from the intestinal mucosa,
      both to exploit the therapeutic potential of stem cells in tissue regeneration
      and to develop treatment models of degenerative disorders of the digestive tract.
      However, the difficulty of propagating cell lines of normal intestinal epithelium
      has impeded research into the molecular mechanisms underlying differentiation of
      stem/progenitor cells into the various intestinal lineages. Several short-term
      organ/organoid and epithelial cell culture models have been described. There is a
      dearth of long-term epithelial and/or stem cell cultures of intestine. With an
      expanding role of stem cells in the treatment of degenerative disorders, there is
      a critical need for additional efforts to develop in vitro models of
      stem/progenitor epithelial cells of intestine. The objective of this review is to
      recapitulate the current status of technologies and knowledge for in vitro
      propagation of intestinal epithelial cells, markers of the intestinal stem cells,
      and gene and protein expression profiles of the intestinal cellular
      differentiation.

PMID- 19580445
TI  - Essential oils against foodborne pathogens and spoilage bacteria in minced meat.
AB  - The antimicrobial activity of essential oils of oregano, thyme, basil, marjoram,
      lemongrass, ginger, and clove was investigated in vitro by agar dilution method
      and minimal inhibitory concentration (MIC) determination against Gram-positive
      (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative strains
      (Escherichia coli and Salmonella Enteritidis). MIC(90%) values were tested
      against bacterial strains inoculated experimentally in irradiated minced meat and
      against natural microbiota (aerobic or facultative, mesophilic, and
      psychrotrophic bacteria) found in minced meat samples. MIC(90%) values ranged
      from 0.05%v/v (lemongrass oil) to 0.46%v/v (marjoram oil) to Gram-positive
      bacteria and from 0.10%v/v (clove oil) to 0.56%v/v (ginger oil) to Gram-negative
      strains. However, the MIC(90%) assessed on minced meat inoculated experimentally
      with foodborne pathogen strains and against natural microbiota of meat did not
      show the same effectiveness, and 1.3 and 1.0 were the highest log CFU/g reduction
      values obtained against tested microorganisms.

PMID- 19580446
TI  - Clustering analysis of Salmonella enterica serovar Typhi isolates in Korea by
      PFGE, ribotying, and phage typing.
AB  - Salmonella enterica serovar Typhi is a Gram-negative bacterium causing the acute
      febrile disease typhoid fever. In Korea from 2004 to 2006, a total of 51
      Salmonella Typhi isolates were identified in stool and blood from healthy
      carriers and patients with or without overseas travel histories. In this study,
      antibiogram, pulsed-field gel electrophoresis (PFGE), and automated ribotyping
      were performed as molecular epidemiological methods with phage typing as a
      classical subtyping tool of the isolates. Only two isolates were multidrug
      resistant and 82.3% of the isolates were susceptible to 16 antimicrobial agents
      tested. When the dendrogram was created based on the PFGE results, the subtypes
      could be clustered into five groups by 80% similarity criterion. The PFGE
      patterns of 31 isolates (60.8%) belonged to Cluster 3, the predominant cluster in
      the study. Three overseas travel-associated cases were differentiated into
      Cluster 4 of which three isolates were nalidixic acid or multidrug resistant.
      Major phage type and ribotype were A and PvuII-436-8-S-6, respectively. This
      study also showed the prevalence of PFGE Cluster 3 in Korea by clustering
      analysis and the link between some typhoid cases and travel to Cambodia, India,
      or Indonesia.

PMID- 19580447
TI  - Salmonellosis outbreaks in the United States due to fresh produce: sources and
      potential intervention measures.
AB  - Foodborne Salmonella spp. is a leading cause of foodborne illness in the United
      States each year. Traditionally, most cases of salmonellosis were thought to
      originate from meat and poultry products. However, an increasing number of
      salmonellosis outbreaks are occurring as a result of contaminated produce.
      Several produce items specifically have been identified in outbreaks, and the
      ability of Salmonella to attach or internalize into vegetables and fruits may be
      factors that make these produce items more likely to be sources of Salmonella. In
      addition, environmental factors including contaminated water sources used to
      irrigate and wash produce crops have been implicated in a large number of
      outbreaks. Salmonella is carried by both domesticated and wild animals and can
      contaminate freshwater by direct or indirect contact. In some cases, direct
      contact of produce or seeds with contaminated manure or animal wastes can lead to
      contaminated crops. This review examines outbreaks of Salmonella due to
      contaminated produce, the potential sources of Salmonella, and possible control
      measures to prevent contamination of produce.

PMID- 19580448
TI  - Molecular characterization of multidrug-resistant strains of Salmonella enterica
      serotype Typhimurium and Monophasic variant (S. 4,[5],12:i:-) isolated from human
      infections in Italy.
AB  - Salmonella enterica serovar Typhimurium (STM) represents the prevalent cause of
      foodborne gastroenteritis in Italy with the majority of isolates exhibiting
      multidrug resistance. A resistant pattern that includes ampicillin (A),
      streptomycin (S), sulfonamide (Su), and tetracycline (T) (ASSuT) but lacks
      resistance to chloramphenicol (C) has recently emerged in Italy among strains of
      STM and of its monophasic variant, S. enterica subspecies enterica serovar S.
      4,[5],12:i:-. With the aim to evaluate their clonal relationships, 553 strains of
      STM and S. 4,[5],12:i:- with the ASSuT and ACSSuT resistance patterns isolated in
      Italy from human infections between 2003 and 2006 were characterized by pulsed
      field gel electrophoresis (PFGE) according to the PulseNet-Europe protocol and
      nomenclature. Among both the STM and S. 4,[5],12:i:- ASSuT strains, the
      predominant PFGE profile was STYMXB.0079 (53.2-73.0% of strains, respectively),
      while the STM ACSSuT strains belonged to the STYMXB.0061 (37.2% of strains) and
      STYMXB.0067 (29.9% of strains). Bionumerics cluster analysis of the nonunique
      PFGE profiles showed that more than 90% of ASSuT and ACSSuT-resistant strains
      were included in two distinct clusters with a genetic homology of 73% each other,
      suggesting that the ASSuT-resistant strains belong to a same clonal lineage
      different from that of the ACSSuT strains. Phage typing showed that 23% of the
      ASSuT STM strains were not typeable and 22.3% were U302. The same phage types
      were observed among the ASSuT strains of S. 4,[5],12:i:-. A different figure was
      observed for the ACSSuT strains: the STM isolates mostly belonged to DT104
      (70.2%), while none of the S. 4,[5],12:i:- strains belonged to this phage type.
      This study indicates that the tetra-resistant ASSuT strains of STM and S.
      4,[5],12:i:-, increasingly isolated in Italy, belong to a same clonal lineage and
      that the S. 4,[5],12:i:- strains circulating in our country mainly derive from
      this STM clonal lineage.

PMID- 19580449
TI  - Prevalence of enteropathogenic Yersinia in Estonian, Latvian, and Russian
      (Leningrad region) pigs.
AB  - Tonsils of 457 fattening pigs from Estonia (n = 151), Latvia (n = 109), and the
      Leningrad Region of Russia (n = 197) were collected between 2004 and 2007 to
      study the prevalence of enteropathogenic Yersinia in slaughter pigs. Yersinia
      enterocolitica and Yersinia pseudotuberculosis were isolated by selective and
      cold enrichment. Pathogenic Y. enterocolitica and Y. pseudotuberculosis were
      identified by PCR targeting the chromosomal genes ail and inv, respectively. The
      presence of the virulence plasmid was confirmed by PCR targeting the virF gene of
      Y. enterocolitica and Y. pseudotuberculosis. The prevalence of ail-positive Y.
      enterocolitica was 89% in Estonia, 64% in Latvia, and 34% in Russia, with 81% of
      ail-positive samples being virF-positive. A statistically significant (p < 0.05)
      difference between Estonian and Latvian pigs and between pigs from Latvia and the
      Leningrad Region of Russia was observed when assuming randomized sampling. Y.
      enterocolitica bioserotype 4/O:3 was the only pathogenic type found. The
      prevalence of inv and virF-positive Y. pseudotuberculosis was higher in Russia
      (7%) than in Latvia (5%) and Estonia (1%), with a statistically significant
      difference between pigs from Estonia and the Leningrad Region of Russia when
      assuming both randomized sampling and clustering at farms. All Y.
      pseudotuberculosis isolates were bioserotype 2/O:3. A total of eight pigs (2%),
      one pig from Latvia and seven pigs from the Leningrad Region of Russia, carried
      both pathogenic Y. enterocolitica and Y. pseudotuberculosis in the tonsils. Cold
      enrichment was found to be a more efficient method compared to selective
      enrichment to isolate both species. Pigs seem to be an important reservoir of
      human enteropathogenic Y. enterocolitica 4/O:3 and Y. pseudotuberculosis 2/O:3 in
      these countries.

PMID- 19580450
TI  - Gene transcription and virulence potential of Listeria monocytogenes strains
      after exposure to acidic and NaCl stress.
AB  - Gene transcription and virulence potential of two strains of Listeria
      monocytogenes, EGD-e and 4140, were compared by quantitative real-time polymerase
      chain reaction and in a Caco-2 in vitro model after exposure to acidic (pH 5.5)
      and NaCl (4.5% w/v) stress. Strain-dependent differences in gene transcription
      were observed both after exposure to shock (six genes) and after long-term
      adaptation to stress (18 genes). In the shock experiments, a transient induction
      of clpC and clpE was seen for both strains, while transient induction of sigB,
      inlA, and inlB was observed for strain 4140 only; actA was only induced in EGD-e
      after NaCl shock. The long-term stress experiments were included to imitate the
      stress conditions encountered by L. monocytogenes when present in food products.
      Long-term adaptation of EGD-e to acidic stress induced transcription of iap and
      repressed flaA, while genes related to stress response and invasion (clpC, clpP,
      inlA, inlB, prfA, and sigB) were induced in 4140. Long-term adaptation of EGD-e
      to NaCl stress increased transcription of genes important for the intracellular
      life cycle (actA, hly, iap, inlA, inlB, plcA, plcB, and prfA), while few changes
      were observed for 4140. Experiments with Caco-2 confirmed that long-term
      adaptation of EGD-e and 4140 to acidic and NaCl stress is capable of increasing
      the virulence potential: an improved adhesion to Caco-2 was observed for both EGD
      e and 4140 after acidic and NaCl stress, and increased invasion was seen for both
      strains after long-term NaCl stress. The fact that several virulence genes were
      up-regulated and that adhesion and invasion properties were increased demonstrate
      that certain environmental conditions in food products might influence the
      virulence potential of L. monocytogenes.

PMID- 19580451
TI  - Regulatory management and communication of risk associated with Escherichia coli
      O157:H7 in ground beef.
AB  - Foodborne illness outbreaks and ground beef recalls associated with Escherichia
      coli O157:H7 have generated substantial consumer risk awareness. Although this
      risk has been assessed and managed according to federal regulation, communication
      strategies may hamper stakeholder perception of regulatory efforts in the face of
      continued E. coli O157:H7 outbreaks associated with ground beef. To mitigate the
      risk of E. coli O157:H7 contamination in ground beef, the beef industry employs
      preharvest and postharvest interventions, while the U.S. Department of
      Agriculture's Food Safety and Inspection Service (FSIS) provides regulatory
      oversight. Policy makers must understand and clearly express that regulation
      allocates, not assumes, responsibility. The FSIS role may be poorly communicated,
      leading consumers, retailers, and others in the farm-to-fork food safety system
      to misrepresent risks and creating unrealistic expectations of regulatory
      responsibility. To improve this risk communication, revisions may be needed in
      FSIS-related documents, Web pages, peer-reviewed publications, and recall
      announcements.

PMID- 19580452
TI  - Salmonella enterica serovar Typhimurium in Mauritius linked to consumption of
      marlin mousse.
AB  - We report the first outbreak of salmonellosis caused by consumption of
      contaminated marlin mousse. Between 29 October and 5 November 2008, at least 53
      persons developed diarrheal illness, all with a history of eating marlin mousse.
      Salmonella spp. that did not produce gas from glucose was isolated from stools of
      26 affected patients and blood culture from one patient. Salmonella sp. isolates
      with the same phenotype were isolated in three samples of marlin mousse
      manufactured on 27 October 2008. The constituents of the mousse were smoked
      marlin, raw eggs, bovine gelatin, oil, and cream. A laboratory investigation of
      one sample of marlin mousse manufactured 3 days later, and the individual
      ingredients sampled a week after production of the contaminated batch were all
      negative for Salmonella. Serotyping and minimum inhibitory concentration
      determination were performed on 12 patient isolates related to the outbreak and
      two mousse isolates. All isolates belonged to Salmonella serovar Typhimurium and
      were pansusceptible to all antimicrobials tested. Pulsed-field gel
      electrophoresis revealed that all the isolates were indistinguishable, thus
      implicating the mousse as the vehicle of the outbreak.

PMID- 19580453
TI  - Examination of the source and extended virulence genotypes of Escherichia coli
      contaminating retail poultry meat.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) are major players in human
      urinary tract infections, neonatal bacterial meningitis, and sepsis. Recently, it
      has been suggested that there might be a zoonotic component to these infections.
      To determine whether the E. coli contaminating retail poultry are possible
      extraintestinal pathogens, and to ascertain the source of these contaminants,
      they were assessed for their genetic similarities to E. coli incriminated in
      colibacillosis (avian pathogenic E. coli [APEC]), E. coli isolated from multiple
      locations of apparently healthy birds at slaughter, and human ExPEC. It was
      anticipated that the retail poultry isolates would most closely resemble avian
      fecal E. coli since only apparently healthy birds are slaughtered, and fecal
      contamination of carcasses is the presumed source of meat contamination.
      Surprisingly, this supposition proved incorrect, as the retail poultry isolates
      exhibited gene profiles more similar to APEC than to fecal isolates. These
      isolates contained a number of ExPEC-associated genes, including those associated
      with ColV virulence plasmids, and many belonged to the B2 phylogenetic group,
      known to be virulent in human hosts. Additionally, E. coli isolated from the
      crops and gizzards of apparently healthy birds at slaughter also contained a
      higher proportion of ExPEC-associated genes than did the avian fecal isolates
      examined. Such similarities suggest that the widely held beliefs about the
      sources of poultry contamination may need to be reassessed. Also, the presence of
      ExPEC-like clones on retail poultry meat means that we cannot yet rule out
      poultry as a source of ExPEC human disease.

PMID- 19580454
TI  - Synergistic effect of high hydrostatic pressure and natural antimicrobials on
      inactivation kinetics of Bacillus cereus in a liquid whole egg and skim milk
      mixed beverage.
AB  - An in-depth study was conducted in order to extend the storage life of a liquid
      whole egg-skim milk (LWE-SM) mixed beverage to enhance its safety and the safety
      of related beverages. Bacillus cereus vegetative cells (1 x 10(8) colony-forming
      units [CFU]/mL) were inoculated in LWE-SM beverages with or without natural
      antimicrobial supplements: flavonol rich-cocoa powder (cocoanOX 12%, CCX) (700
      ppm), vanillin (700 ppm), anise (700 ppm), and cinnamon (700 ppm). B. cereus
      cells were maintained at 10 degrees C for 10 days in the different beverages to
      test the bacteriostatic or inhibitory effect of the aforementioned ingredients.
      Beverages were treated with high hydrostatic pressure (HHP) technology and stored
      at 10 degrees C for 15 days after treatment. All natural antimicrobials reduced
      the micro(max) values and increased the lag phase time of B. cereus, and Gompertz
      growth curves showed different inhibitory effects depending on the substance. The
      maximum inhibitory effect (1.330 log cycle reduction) was achieved in LWE-SM
      cinnamon-supplemented beverage. The maximum inactivation achieved by HHP in LWE
      SM beverage was a reduction of around 3.89 +/- 0.25 log cycles at 300 MPa for 12
      minutes. When supplemented beverages were treated under the same conditions,
      enhanced inactivation levels were achieved. This increased inactivation can be
      attributed to a synergistic effect when the LWE-SM was supplemented with flavonol
      rich cocoa powder, cinnamon, and vanillin. The maximum synergistic effect was
      observed in LWE-SM-CCX-supplemented beverage. During the refrigerated storage of
      B. cereus HHP-treated cells in beverages to which antimicrobials had been added,
      the inhibitory effect was dependent on the previously applied pressure level.

PMID- 19580455
TI  - Effect of Eleutherine americana Merr. extract on enzymatic activity and
      enterotoxin production of Staphylococcus aureus in broth and cooked pork.
AB  - Crude ethanolic extract from the bulb of Eleutherine americana was investigated
      for its inhibitory activities against lipase and protease enzymes and enterotoxin
      production by Staphylococcus aureus. Eleven isolates that demonstrated high
      enzyme activity with three reference strains were selected to study the effect of
      extract on enzyme production. Exposure of the isolates to subminimal inhibitory
      concentrations, (1/2) minimum inhibitory concentration (MIC) (125 microg/mL), and
      (1/4)MIC (62.5 microg/mL) of the crude extract resulted in both partial and total
      inhibition of lipase and protease enzymes. About 15% of the 106 isolates were
      positive for enterotoxin production with staphylococcal enterotoxin A (11.3%),
      enterotoxin B (3.7%), and enterotoxin C (10.3%), and no enterotoxin D was
      produced. The production of staphylococcal enterotoxins A-D in the presence or
      absence of the crude extract was carried out. In the broth system, the extract
      reduced enterotoxin production at subminimal inhibitory concentrations compared
      with the control. At MIC, total enterotoxin inhibition was observed for
      enterotoxin C production, whereas synthesis of enterotoxins A, B, and D was
      totally eliminated at 2MIC. The food system study revealed that the extract could
      delay production of enterotoxins A, B, and C compared with the control. The
      extract at 2 mg/mL delayed production of toxins A and C for 8 and 4 h, while
      toxin B was not detected in the pork at 48 h. The ability of E. americana extract
      to inhibit lipase and protease enzymes and to delay enterotoxin production in
      food could present it as a novel food additive to combat the growth of S. aureus
      in food.

PMID- 19580456
TI  - Oral administration of insulin receptor-interacting lectins leads to an
      enhancement in the hematopoietic stem and progenitor cell pool of mice.
AB  - Lectins form an important constituent of our daily diet, and thus, it is
      essential that their effect(s) on various tissues be examined systematically in
      order to assess whether they are beneficial or detrimental to human health. We
      examined the effect of oral administration of two dietary lectins that were
      isolated from banana (BL) and garlic (GL)-two quite commonly consumed food items
      on the hematopoiesis of mice. Balb/c mice were fed weekly with lectins and their
      marrow mononuclear cells (MNCs) were subjected to various hematopoietic
      stem/progenitor (HSPC)-specific phenotypic and functional assays. It was observed
      that the lectin-fed mice harbored a considerably increased HSPC pool in their
      marrow. Marrow-derived MNCs isolated from these lectin-fed mice gave rise to
      large-sized colony-forming unit-fibroblast (CFU-F) colonies indicating that the
      lectins had a salutary effect on the stromal compartment. The molecular
      mechanisms involved in the process were examined by using a stromal cell line
      model, M210B4. The lectins pulled down pro-insulin and insulin receptors in an
      immunoprecipitation experiment and activated extracellular signal-regulated
      kinase (ERK) signaling in the treated cells, in a manner comparable to insulin,
      both in terms of kinetics as well as extent. M210B4 cells incubated with BL, GL,
      or insulin showed reduced levels of reactive oxygen species, suggesting that
      perhaps the lectins protected the stem cell pool of mice by activating ERK
      signaling and reducing the oxidative stress in the niche. Our data suggest that
      these lectins may serve as micronutrients for therapeutic purposes in
      hematological deficiencies.

PMID- 19580457
TI  - Randomized trial of intensive bisphosphonate treatment versus symptomatic
      management in Paget's disease of bone.
AB  - Bisphosphonates are widely regarded as the treatment of choice for Paget's
      disease of bone (PDB) because of their potent inhibitory effects on bone
      turnover, but the effects of bisphosphonate therapy on symptoms and complications
      of PDB have been little studied. Here we report the results of a randomized trial
      that compared the effects of symptomatic treatment with intensive bisphosphonate
      therapy in a cohort of 1324 patients with PDB who were followed up for a median
      of 3 years (range 2 to 5 years). The symptomatic treatment group was treated only
      if they had pagetic bone pain, for which they were first given analgesics or anti
      inflammatory drugs, followed by bisphosphonates if they did not respond. The
      intensive group received repeat courses of bisphosphonates irrespective of
      symptoms with the aim of reducing and maintaining serum alkaline phosphatase
      (ALP) levels within the normal range. The endpoints were fracture, orthopedic
      surgery, quality of life, bone pain, and hearing thresholds. Serum ALP levels
      were significantly lower in the intensive treatment group than in with the
      symptomatic treatment group within 4 months of commencing treatment and remained
      lower throughout the study (p < .001). There was no difference between the groups
      in quality of life (as assessed by the SF36 questionnaire), in overall bodily
      pain, or in pagetic bone pain. Hearing thresholds, as assessed by audiometry did
      not change significantly and did not differ between the treatment groups.
      Clinical fractures occurred in 46 of 661 patients (7.0%) in the intensive
      treatment group compared with 49 of 663 patients (7.4%) in the symptomatic
      treatment group, and orthopedic surgery was required in 50 of 661 patients (7.3%)
      in the intensive treatment group and in 55 of 663 patients (8.3%) in the
      symptomatic treatment group. These differences were not significant. Subgroup
      analyses of patients with elevated ALP levels at baseline and those who did or
      did not receive bisphosphonates during the study yielded similar results to those
      in the study group as a whole. We conclude that striving to maintain normal ALP
      levels with intensive bisphosphonate therapy confers no clinical advantage over
      symptom-driven management in patients with established PDB. Neither management
      strategy had a significant beneficial impact on pain or quality of life (Clinical
      trial registration number ISRCTN12989577).

PMID- 19580458
TI  - Differentiation-dependent association of phosphorylated extracellular signal
      regulated kinase with the chromatin of osteoblast-related genes.
AB  - The ERK/MAP kinase pathway is an important regulator of gene expression and
      differentiation in postmitotic cells. To understand how this pathway controls
      gene expression in bone, we examined the subnuclear localization of P-ERK in
      differentiating osteoblasts. Induction of differentiation was accompanied by
      increased ERK phosphorylation and expression of osteoblast-related genes,
      including osteocalcin (Bglap2) and bone sialoprotein (Ibsp). Confocal
      immunofluorescence microscopy revealed that P-ERK colocalized with the RUNX2
      transcription factor in the nuclei of differentiating cells. Interestingly, a
      portion of this nuclear P-ERK was directly bound to the proximal promoter regions
      of Bglap2 and Ibsp. Furthermore, the level of P-ERK binding to chromatin
      increased with differentiation, whereas RUNX2 binding remained relatively
      constant. The P-ERK-chromatin interaction was seen only in RUNX2-positive cells,
      required intact RUNX2-selective enhancer sequences, and was blocked with MAPK
      inhibition. These studies show for the first time that RUNX2 specifically targets
      P-ERK to the chromatin of osteoblast-related genes, where it may phosphorylate
      multiple substrates, including RUNX2, resulting in altered chromatin structure
      and gene expression.

PMID- 19580459
TI  - Prevalence and trends in low femur bone density among older US adults: NHANES
      2005-2006 compared with NHANES III.
AB  - Hip fracture incidence appears to be declining in the United States, but changes
      in bone mineral density (BMD) of the population have not been evaluated. We used
      femur BMD data from the National Health and Nutrition Examination Survey (NHANES)
      2005-2006 to estimate the prevalence of low femoral BMD in adults age 50 years
      and older and compared it with estimates from NHANES III (1988-1994). Dual-energy
      X-ray absorptiometry systems (pencil-beam geometry in NHANES III, fan-beam
      geometry in NHANES 2005-2006) were used to measure femur BMD, and World Health
      Organization (WHO) definitions of low BMD were used to categorize skeletal
      status. In 2005-2006, 49% of older US women had osteopenia and 10% had
      osteoporosis at the femur neck. In men, 30% had femur neck osteopenia and 2% had
      femur neck osteoporosis. An estimated 5.3 million older men and women had
      osteoporosis at the femur neck, and 34.5 million more had osteopenia in 2005
      2006. When compared with NHANES III, the age-adjusted prevalence of femur neck
      osteoporosis in NHANES 2005-2006 was lower in men (by 3 percentage units) and
      women (by 7 percentage units) overall and among non-Hispanic whites. Changes in
      body mass index or osteoporosis medication use between surveys did not fully
      explain the decline in osteoporosis. Owing to the increase in the number of older
      adults in the US population, however, more older adults had low femur neck BMD
      (osteoporosis + osteopenia) in 2005-2006 than in 1988-1994. Thus, despite the
      decline in prevalence, the estimated number of affected older adults in 2005-2006
      remained high.

PMID- 19580461
TI  - A randomized, controlled dose-ranging study of risedronate in children with
      moderate and severe osteogenesis imperfecta.
AB  - Moderate to severe osteogenesis imperfecta is associated with multiple fractures
      in childhood. There are no published data regarding the effects of third
      generation bisphosphonates in these children. This randomized study investigated
      which of three different doses of risedronate was most effective in reducing
      fracture incidence. We randomly assigned 53 children with moderate to severe
      osteogenesis imperfecta to receive 0.2, 1, or 2 mg/kg per week of risedronate. We
      assessed safety, fracture incidence, and bone measurement outcomes at 3, 6, 12,
      18, and 24 months. At 24 months, 69% of children assigned 0.2 mg/kg per week had
      had new fractures compared with 44% receiving 1 mg/kg per week and 75% receiving
      2 mg/kg per week. Poisson regression with age and prior fracture as covariates
      showed that there was no difference in incident nonvertebral fracture between
      groups. Fracture rate diminished in each group during the trial compared with
      previous the 2 years (p = .005). Lumbar spine bone mineral density increased
      significantly (p = .009) only in the 2 mg/kg per week group. Long bone bowing
      deformities reduced more in children receiving 1 or 2 mg/kg per week of
      risedronate [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48-0.93 per
      unit increase in risedronate dose, p = .015]. There were no serious adverse
      events. Bone mass increased and bowing deformities reduced with increasing
      risedronate dose. Children suffered fewer fractures irrespective of risedronate
      dose. The most appropriate dose of risedronate for children with moderate to
      severe osteogenesis imperfecta in this study was 2 mg/kg per week.

PMID- 19580462
TI  - Restoration of regenerative osteoblastogenesis in aged mice: modulation of TNF.
AB  - Skeletal changes accompanying aging are associated with both increased risk of
      fractures and impaired fracture healing, which, in turn, is due to compromised
      bone regeneration potential. These changes are associated with increased serum
      levels of selected proinflammatory cytokines, e.g., tumor necrosis factor alpha
      (TNF-alpha). We have used a unique model of bone regeneration to demonstrate (1)
      that aged-related deficits in direct bone formation can be restored to young mice
      by treatment with TNF blockers and (2) that the cyclin-dependent kinase inhibitor
      p21 is a candidate for mediation of the osteoinhibitory effects of TNF. It has
      been hypothesized recently that TNF antagonists may represent novel anabolic
      agents, and we believe that the data presented here represent a successful test
      of this hypothesis.

PMID- 19580464
TI  - Low maternal vitamin D status and fetal bone development: cohort study.
AB  - Recent findings suggest that maternal vitamin D insufficiency during pregnancy
      has consequences for the offspring's bone health in later life. To investigate
      whether maternal vitamin D insufficiency affects fetal femur growth in ways
      similar to those seen in childhood rickets and study the timing during gestation
      of any effect of maternal vitamin D status, we studied 424 pregnant women within
      a prospective longitudinal study of maternal nutrition and lifestyle before and
      during pregnancy (Southampton Women's Survey). Using high-resolution 3D
      ultrasound, we measured fetal femur length and distal metaphyseal cross-sectional
      area, together with the ratio of femoral metaphyseal cross-sectional area to
      femur length (femoral splaying index). Lower maternal 25-hydroxyvitamin vitamin D
      concentration was not related to fetal femur length but was associated with
      greater femoral metaphyseal cross-sectional area and a higher femoral splaying
      index at 19 weeks' gestation [r = -0.16, 95% confidence interval (CI) -0.25 to 
      0.06 and r = -0.17, 95% CI -0.26 to -0.07, respectively] and at 34 weeks'
      gestation (r = -0.10, 95% CI -0.20 to 0.00 and r = -0.11, 95% CI -0.21 to -0.01,
      respectively). Three groups of women were identified with 25-hydroxyvitamin
      vitamin D concentrations that were sufficient/borderline (> 50 nmol/L, 63.4%),
      insufficient (25 to 50 nmol/L, 30.7%), and deficient (< or = 25 nmol/L, 5.9%).
      Across these groups, the geometric mean femoral splaying indices at 19 weeks'
      gestation increased from 0.074 (sufficient/borderline) to 0.078 (insufficient)
      and 0.084 (deficient). Our observations suggest that maternal vitamin D
      insufficiency can influence fetal femoral development as early as 19 weeks'
      gestation. This suggests that measures to improve maternal vitamin D status
      should be instituted in early pregnancy.

PMID- 19580463
TI  - Cancer treatment dosing regimens of zoledronic acid result in near-complete
      suppression of mandible intracortical bone remodeling in beagle dogs.
AB  - Bisphosphonate doses used in cancer treatment are substantially higher than those
      used for osteoporosis. Little is known about the effects of these high doses on
      tissue-level remodeling suppression. The aim of this study was to assess the
      effects of cancer dosing regimens of zoledronic acid on tissue-level bone
      remodeling at different skeletal sites. Skeletally mature female beagle dogs were
      treated with monthly intravenous infusions of vehicle (VEH, saline) or zoledronic
      acid (ZOL, 0.067 mg/kg); an additional group of animals was treated daily with
      oral alendronate (ALN, 0.2 mg/kg/day). Doses of ZOL and ALN were, on a milligram
      per kilogram basis, consistent with those used for cancer and osteoporosis,
      respectively. Following either 3 or 6 months of treatment, animals were
      euthanized, and mandible, rib, and tibia were processed for dynamic bone
      histology. There was no evidence of oral lesions or bone matrix necrosis in the
      mandibles of any animals. After 3 months, the rate of intracortical bone
      remodeling in the mandible was significantly suppressed with ZOL (-95%) compared
      with VEH; by 6 months, ZOL had produced nearly complete suppression (-99%)
      compared with VEH. ZOL also significantly suppressed remodeling in the rib cortex
      at both 3 (-83%) and 6 (-85%) months compared with VEH; tibia cortex bone
      formation rate was nonsignificantly lower with ZOL treatment (-68% to -75%).
      Remodeling suppression in ZOL-treated animals was significantly greater than in
      ALN-treated animals at both the mandible and the rib; ALN and VEH were not
      different for any of the assessed parameters at any of the sites. Compared across
      skeletal sites, the absolute level of remodeling suppression with ZOL treatment
      was significantly greater at sites with higher remodeling, whereas the percent
      reduction was similar among the sites. These results document nearly complete
      intracortical remodeling suppression resulting from monthly intravenous
      zoledronic acid dosing, with changes being most dramatic at the mandible.

PMID- 19580465
TI  - Mineralization density distribution of postmenopausal osteoporotic bone is
      restored to normal after long-term alendronate treatment: qBEI and sSAXS data
      from the fracture intervention trial long-term extension (FLEX).
AB  - Long-term treatment studies showed that the therapeutic effects of alendronate
      (ALN) were sustained over a 10-year treatment period. However, data on the
      effects on intrinsic bone material properties by long-term reduction of bone
      turnover are still sparse. We analyzed transiliacal bone biopsies of a subgroup
      of 30 Fracture Intervention Trial Long-Term Extension (FLEX) participants (n = 6
      were treated for 10 years with ALN at dose of 10 mg/day, n = 10 were treated for
      10 years with ALN at dose of 5 mg/day, and n = 14 were treated for 5 years with
      ALN plus a further 5 years with placebo) by quantitative backscattered electron
      imaging (qBEI) and scanning small-angle X-ray scattering (sSAXS) to determine the
      bone mineralization density distribution (BMDD) and the mineral particle
      thickness parameter T. BMDD data from these FLEX participants were compared with
      those from a previously published healthy population (n = 52). Compared with 5
      years of ALN plus 5 years of placebo 10 years of ALN treatment (independent of
      the dose given) did not produce any difference in any of the BMDD parameters: The
      weighted mean (Ca(mean)), the typical calcium concentration (Ca(peak)), the
      heterogeneity of mineralization (Ca(width)), the percentage of low-mineralized
      bone areas (Ca(low)), and the portion of highly mineralized areas (Ca(high)) were
      not different for the patients who continued ALN from those who stopped ALN after
      5 years. Moreover, no significant differences for any of the BMDD parameters
      between the FLEX participants and the healthy population could be observed. In
      none of the investigated cases were abnormally high mineralization or changes in
      mineral particle thickness observed (Ca(high) and T were both in the normal
      range). The findings of this study support the recommendation that antiresorptive
      treatment with ALN should be maintained for 5 years. Even with longer treatment
      durations of up to 10 years, though, no negative effects on bone matrix
      mineralization were observed.

PMID- 19580466
TI  - Mapping of human autoantibody binding sites on the calcium-sensing receptor.
AB  - Previously, we have demonstrated the presence of anti-calcium-sensing receptor
      (CaSR) antibodies in patients with autoimmune polyglandular syndrome type 1
      (APS1), a disease that is characterized in part by hypoparathyroidism involving
      hypocalcemia, hyperphosphatemia, and low serum levels of parathyroid hormone. The
      aim of this study was to define the binding domains on the CaSR of anti-CaSR
      antibodies found in APS1 patients and in one patient suspected of having
      autoimmune hypocalciuric hypercalcemia (AHH). A phage-display library of CaSR
      peptides was constructed and used in biopanning experiments with patient sera.
      Selectively enriched IgG-binding peptides were identified by DNA sequencing, and
      subsequently, immunoreactivity to these peptides was confirmed in ELISA. Anti
      CaSR antibody binding sites were mapped to amino acid residues 41-69, 114-126,
      and 171-195 at the N-terminal of the extracellular domain of the receptor. The
      major autoepitope was localized in the 41-69 amino acid sequence of the CaSR with
      antibody reactivity demonstrated in 12 of 12 (100%) APS1 patients with anti-CaSR
      antibodies and in 1 AHH patient with anti-CaSR antibodies. Minor epitopes were
      located in the 114-126 and 171-195 amino acid domains, with antibody reactivity
      shown in 5 of 12 (42%) and 4 of 12 (33%) APS1 patients, respectively. The results
      indicate that epitopes for anti-CaSR antibodies in the AHH patient and in the
      APS1 patients who were studied are localized in the N-terminal of the
      extracellular domain of the receptor. The present work has demonstrated the
      successful use of phage-display technology in the discovery of CaSR-specific
      epitopes targeted by human anti-CaSR antibodies.

PMID- 19580468
TI  - Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of
      growth plate cartilage but does not inhibit the induction of mineralization.
AB  - Initiation of mineralization during endochondral ossification is a multistep
      process and has been assumed to correlate with specific interactions of annexins
      A5 and A6 and collagens. However, skeletal development appears to be normal in
      mice deficient for either A5 or A6, and the highly conserved structures led to
      the assumption that A5 and A6 may fulfill redundant functions. We have now
      generated mice deficient of both proteins. These mice were viable and fertile and
      showed no obvious abnormalities. Assessment of skeletal elements using
      histologic, ultrastructural, and peripheral quantitative computed tomographic
      methods revealed that mineralization and development of the skeleton were not
      significantly affected in mutant mice. Otherwise, global gene expression analysis
      showed subtle changes at the transcriptome level of genes involved in cell growth
      and intermediate metabolism. These results indicate that annexins A5 and A6 may
      not represent the essential annexins that promote mineralization in vivo.

PMID- 19580467
TI  - Potential mediators of the mortality reduction with zoledronic acid after hip
      fracture.
AB  - Zoledronic acid reduces the risk of death by 28% after hip fracture, but the
      mechanisms are not known. This exploratory analysis sought to identify potential
      pathways for the reduction in mortality with zoledronic acid after hip fracture.
      This was a retrospective analysis of a randomized, controlled trial. Patients
      with recent hip fracture (n = 2111) were treated with zoledronic acid or placebo
      infusion yearly, as well as calcium and vitamin D supplementation. Causes of
      death were adjudicated by a blinded central review committee. Baseline
      comorbidities, events occurring during the study period, including subsequent
      fracture, change in bone density, infections, cardiovascular events, arrhythmias,
      and falls, were included in multivariable analyses. In a model adjusted for
      baseline risk factors, zoledronic acid reduced the risk of death by 25% [95%
      confidence interval (CI) 0.58-0.97). The effect was consistent across most
      subgroups. Subsequent fractures were significantly associated with death (hazard
      ratio 1.72, 95% CI 1.17-2.51) but explained only 8% of the zoledronic acid
      effect. Adjusting for acute events occurring during follow-up eliminated the
      death benefit, and zoledronic acid-treated subjects were less likely to die from
      pneumonia (interaction p = .04) and arrhythmias (interaction p = .02) than
      placebo-treated subjects. Only 8% of zoledronic acid's death benefit is due to a
      reduction in secondary fractures. Zoledronic acid may have an effect on
      cardiovascular events and pneumonia. Further studies of zoledronic acid in other
      acute illnesses may be warranted.

PMID- 19580469
TI  - Risedronate reduces intracortical porosity in women with osteoporosis.
AB  - Nonvertebral fractures account for 80% of all fractures and their accompanying
      morbidity and mortality. Despite this, the effect of drug therapy on cortical
      morphology has received limited attention, partly because cortical bone is
      believed to remodel less and decrease less with age than trabecular bone.
      However, the haversian canals traversing the cortex provide a surface for
      remodeling that produces bone loss, porosity, and cortical fragility. We
      developed a new method of 3D micro-computed tomography (microCT) to quantify
      intracortical porosity and the effects of treatment. Women with osteoporosis
      randomized to risedronate (5 mg/day, n = 28) or placebo (n = 21) had paired
      transiliac biopsies at baseline and 5 years imaged using 3D microCT. Pores
      determined from 8 to 12 slices were stratified by their minor axis length into
      those 25 to 100 microm (closing cone of haversian canals), 100 to 300 microm
      (cutting cone of haversian canals), and >300 microm (coalescent cavities).
      Porosity was analyzed as pore area (percent bone area) and pore density (pore
      number/mm(2)). Medians are reported. Risedronate reduced pore area in the 25 to
      100, 100 to 300, and 300 to 500 microm ranges over 5 years (p = .0008, .04, NS,
      respectively) corresponding to an 18% to 25% reduction. In the placebo group,
      pore area was unchanged. At 5 years, pore area and pore number/mm(2) in the 25 to
      100 microm range were each 17% lower in the risedronate group than in the placebo
      group (p = .02 and .04, respectively). Risedronate is likely to maintain bone
      strength and reduce nonvertebral fracture risk in part by reducing remodeling and
      therefore the number and size of intracortical cavities.

PMID- 19580470
TI  - A nested case-control study of multiple myeloma risk and uranium exposure among
      workers at the Oak Ridge Gaseous Diffusion Plant.
AB  - The primary risk factors of multiple myeloma are age, race and sex, but several
      studies have found an association between radiological hazards and multiple
      myeloma. The purpose of this nested case-control study was to investigate whether
      workers with chronic low-level exposure to internally deposited uranium at the
      Oak Ridge Gaseous Diffusion Plant in eastern Tennessee were at higher risk of
      dying of multiple myeloma than those without occupational exposure to uranium,
      with the consideration of potential confounders of external ionizing radiation
      and occupational chemical hazards such as mercury, nickel and trichloroethylene.
      The main analyses were carried out using conditional logistic regression on 98
      cases and 490 controls (five controls matched to each case on gender, race and
      age at risk). Our study showed a weak association between internal uranium dose
      estimated from urinalysis results and multiple myeloma risk: OR = 1.04 (95% CI
      1.00-1.09) at 10 microGy with the inclusion of other risk factors. The parameter
      estimates and the corresponding odds ratios were very similar when internal doses
      were imputed for subjects without urine samples. Further studies that include
      updating this cohort and combining with workers from other gaseous diffusion
      plants are needed to investigate the relationship between multiple myeloma risk
      and radiation or other chemical exposures.

PMID- 19580471
TI  - Application of a novel microdosimetry analysis and its radiobiological
      implication for high-LET radiation.
AB  - For short-range high-LET radiation therapy, the biological effects are strongly
      affected by the heterogeneity of the specific energy distribution delivered to
      tumor cells. Three-dimensional information at the cellular level is ideal for
      this type of study, but it is extremely difficult to obtain. In this paper, a
      novel microdosimetry analysis, which obtains the specific energy distribution
      directly from the morphological information in individual autoradiographic
      sections, is applied to in vivo human glioblastoma multiforme and normal brain
      tissue in boron neutron capture therapy. Specific energy distributions were
      obtained for both specimens, and they are consistent with a uniform boron
      microdistribution. We also used a biophysical model for cell survival analysis
      based on the specific energy and were able to bridge it with the model based on
      the corresponding macroscopic parameter (dose) using existing experimental data.
      The survival constant for the microscopic model was determined; cell survival
      curves were predicted for uniform and non-uniform source distributions, i.e.,
      sources and cell nuclei bound together totally or only partially. The results
      indicate that the behavior of the survival curve can vary widely, which may have
      important clinical implications.

PMID- 19580472
TI  - Evidence of extranuclear cell sensitivity to alpha-particle radiation using a
      microdosimetric model. I. Presentation and validation of a microdosimetric model.
AB  - A microdosimetric model that makes it possible to consider the numerous
      biological and physical parameters of cellular alpha-particle irradiation by
      radiolabeled mAbs was developed. It allows for the calculation of single-hit and
      multi-hit distributions of specific energy within a cell nucleus or a whole cell
      in any irradiation configuration. Cells are considered either to be isolated or
      to be packed in a monolayer or a spheroid. The method of calculating energy
      deposits is analytical and is based on the continuous-slowing-down approximation.
      A model of cell survival, calculated from the microdosimetric spectra and the
      microdosimetric radiosensitivity, z(0), was also developed. The algorithm of
      calculations was validated by comparison with two general Monte Carlo codes:
      MCNPX and Geant4. Microdosimetric spectra determined by these three codes showed
      good agreement for numerous geometrical configurations. The analytical method was
      far more efficient in terms of calculation time: A gain of more than 1000 was
      observed when using our model compared with Monte Carlo calculations. Good
      agreements were also observed with previously published results.

PMID- 19580473
TI  - Evidence of extranuclear cell sensitivity to alpha-particle radiation using a
      microdosimetric model. II. Application of the microdosimetric model to
      experimental results.
AB  - A microdosimetric model was used to analyze the results of experimental studies
      on cells of two lymphoid cell lines (T2 and Ada) irradiated with (213)Bi
      radiolabeled antibodies. These antibodies targeted MHC/peptide complexes. The
      density of target antigen could be modulated by varying the concentration of the
      peptide loaded onto the cells. This offered the possibility of changing the ratio
      of specific (from cell-bound antibody) to non-specific (from antibody present in
      the supernatant) irradiation. For both cell lines, survival plotted as a function
      of the mean absorbed dose was a decreasing exponential. For the T2 cells, the
      microdosimetric sensitivity calculated for the whole cell was equal whether the
      irradiation was non-specific (z(0) = 0.12 +/- 0.02 Gy) or specific (z(0) = 0.12
      +/- 0.09 Gy). Similar results were obtained for Ada cells. These results
      constitute a biological validation of the microdosimetric model. For both cells,
      the measured cell mortality was greater than the percentage of hit cells
      calculated with the model at low mean absorbed doses. This observation thus
      suggests bystander effects. It poses the question of the relevance of the mean
      absorbed dose to the cell nuclei. A new concept in cellular dosimetry taking into
      account cytoplasm or membrane irradiation and bystander modeling appears to be
      needed.

PMID- 19580474
TI  - Simplified structure of a new model to describe urinary excretion of plutonium
      after systemic, liver or pulmonary contamination of rats associated with Ca-DTPA
      treatments.
AB  - This study validates, by targeted experiments, several modeling hypotheses for
      interpretation of urinary excretion of plutonium after Ca-DTPA treatments.
      Different formulations and doses of Ca-DTPA were administered to rats before or
      after systemic, liver or lung contamination with various chemical forms of
      plutonium. The biokinetics of plutonium was also characterized after i.v.
      injection of Pu-DTPA. Once formed, Pu-DTPA complexes are stable in most
      biological environments. Pu-DTPA present in circulating fluids is rapidly
      excreted in the urine, but 2-3% is retained, mainly in soft tissues, and is then
      excreted slowly in the urine after transfer to blood. Potentially, all
      intracellular monoatomic forms of plutonium could be decorporated after DTPA
      internalization involving slow urinary excretion of Pu-DTPA with half-lives
      varying from 2.5 to 6 days as a function of tissue retention. The ratio of fast
      to slow urinary excretion of Pu-DTPA depends on both plutonium contamination and
      Ca-DTPA treatment. Fast urinary excretion of Pu-DTPA corresponds to extracellular
      decorporation that occurs beyond a threshold of the free DTPA concentration in
      circulating fluids. Slow excretion corresponds mostly to intracellular
      decorporation and depends on the amount of intracellular DTPA. From these
      results, the structure of a simplified model is proposed for interpretation of
      data obtained with Ca-DTPA treatments after systemic, wound or pulmonary
      contamination by plutonium.

PMID- 19580475
TI  - Migration of skin dendritic cells in response to ionizing radiation exposure.
AB  - We describe an imaging assay that monitors the migration of two unique subsets of
      immune dendritic cells (DC), interstitial dendritic cells (iDC) and Langerhans
      cells (LC), found in the dermal and epidermal layers of skin, respectively. Using
      this assay, we study responses of these cells to ionizing radiation. Results
      obtained using whole-mount histology and fluorescence microscopy suggest that
      ionizing radiation triggered the migration of both major histocompatibility
      complex (MHC) class II(+) iDC and Langerin(+) LC in a dose- and time-dependent
      manner. Migration appeared to be limited by local administration of recombinant
      IL-12, a potent immunostimulatory cytokine known to induce DNA repair. Those
      findings were extended to an in vivo model by injecting fluorescently conjugated
      anti-MHC class II antibodies intradermally into the ears of live, anesthetized
      mice and visualizing the DC population in the same ear before and after radiation
      exposure using confocal microscopy.

PMID- 19580477
TI  - Comparison of several radiation effects in human MCF10A mammary epithelial cells
      cultured as 2D monolayers or 3D acinar stuctures in matrigel.
AB  - It has been argued that the cell-cell and cell-matrix interaction networks in
      normal tissues are disrupted by radiation and that this largely controls many of
      the most important cellular radiation responses. This has led to the broader
      assertion that individual cells in normal tissue or a 3D normal-tissue-like
      culture will respond to radiation very differently than the same cells in a 2D
      monolayer culture. While many studies have shown that, in some cases, cell-cell
      contact in spheroids of transformed or tumor cell lines can alter radiation
      responses relative to those for the same cells in monolayer cultures, a question
      remains regarding the possible effect of the above-mentioned disruption of
      signaling networks that operate more specifically for cells in normal tissues or
      in a 3D tissue-like context. To test the generality of this notion, we used human
      MCF-10A cells, an immortalized mammary epithelial cell line that produces acinar
      structures in culture with many properties of human mammary ducts. We compared
      the dose responses for these cells in the 2D monolayer and in 3D ductal or acinar
      structures. The responses examined were reproductive cell death, induction of
      chromosomal aberrations, and the levels of gamma-H2AX foci in cells after single
      acute gamma-ray doses and immediately after 20 h of irradiation at a dose rate of
      0.0017 Gy/min. We found no significant differences in the dose responses of these
      cells in 2D or 3D growth conditions. While this does not mean that such
      differences cannot occur in other situations, it does mean that they do not
      generally or necessarily occur.

PMID- 19580476
TI  - The somatostatin analog SOM230 (pasireotide) ameliorates injury of the intestinal
      mucosa and increases survival after total-body irradiation by inhibiting exocrine
      pancreatic secretion.
AB  - Somatostatin analogs ameliorate intestinal injury after localized irradiation.
      This study investigated whether SOM230, a novel, metabolically stable analog with
      broad receptor affinity, reduces intestinal injury and lethality in mice exposed
      to total-body irradiation (TBI). Male CD2F1 mice were exposed to 7-15 Gy TBI.
      Twice-daily administration of SOM230 (1, 4 or 10 mg/kg per day) or vehicle was
      started either 2 days before or 4 h after TBI and continued for either 14 or 21
      days. Parameters of intestinal and hematopoietic radiation injury, bacterial
      translocation, and circulating cytokine levels were assessed. Animal survival was
      monitored for up to 30 days. SOM230 increased survival (P < 0.001) and prolonged
      survival time (P < 0.001) whether administration was initiated before or after
      TBI. There was no benefit from administration for 21 compared to 14 days. The
      survival benefit of SOM230 was completely reversed by co-administration of
      pancreatic enzymes (P = 0.009). Consistent with the presumed non-cytoprotective
      mechanism of action, SOM230 did not influence hematopoietic injury or intestinal
      crypt lethality. However, SOM230 preserved mucosal surface area (P < 0.001) and
      reduced bacterial translocation in a dose-dependent manner (P < 0.001).
      Circulating IL-12 levels were reduced in SOM230-treated mice (P = 0.007). No
      toxicity from SOM230 was observed. SOM230 enhances animal survival whether
      administration begins before or after TBI; i.e., it is effective both as a
      protector and as a mitigator. The mechanism likely involves reduction of
      intraluminal pancreatic enzymes. Because of its efficacy and favorable safety
      profile, SOM230 is a promising countermeasure against radiation and should
      undergo further development.

PMID- 19580478
TI  - UVB radiation induces persistent activation of ribosome and oxidative
      phosphorylation pathways.
AB  - Ultraviolet B (UVB) radiation has strong biological effects and modulates the
      expression of many genes. The major biological pathways affected by UVB radiation
      remain controversial. In this work, we used a loop-design microarray approach and
      applied rigorous statistical analyses to identify differentially regulated genes
      at 4, 8, 16 or 24 h after UVB irradiation. The most prominent biological
      categories in lists of differentially regulated gene sets were extracted by
      functional enrichment analysis. With this approach, we determined that genes
      participating in two prime cellular processes, the ribosome pathway and the
      oxidative phosphorylation pathway, were persistently activated after UVB
      irradiation. Mitochondrial activity assays confirmed increased activity for up to
      24 h after UVB irradiation. These results suggest that the persistent activation
      of ribosome and oxidative phosphorylation pathways may have a key role in UVB
      radiation-induced cellular responses. For the first time, the specific cellular
      pathways that respond to UVB radiation consistently and persistently can be
      delineated with confidence using a loop-design microarray approach and functional
      bioinformatics analysis. The results of this study offer further insight into UVB
      radiation-induced stress responses.

PMID- 19580479
TI  - Transient dephosphorylation of p53 serine 376 as an early response to ionizing
      radiation.
AB  - In a previous paper we reported that the cytoplasmic sequestered p53 in cells of
      the SK-N-SH neuroblastoma cell line could be induced to translocate to the
      nucleus by exposure to ionizing radiation. We have extended these studies to
      determine the fate of p53 in HCT116 colorectal carcinoma cells where constitutive
      p53 protein resides in the nucleus. A continuous increase in the nuclear p53
      protein was observed in irradiated cells beginning 1 h after irradiation that
      persisted for 8 h. Surprisingly, immunofluorescence microscopy revealed a
      transient, rapid and sensitive increase in a radiation-induced nuclear
      dephosphorylated p53 using antibody PAb421, which detects p53 when serine 376 is
      dephosphorylated. The PAb421 epitope was detectable after exposure to radiation
      doses as low as 0.5 cGy and was 10 to 20 times more sensitive compared to
      detection of p53 protein levels. The results are consistent with a radiation
      induced, sensitive and rapid dephosphorylation of p53 at serine 376. The rapid
      increase in the nuclear PAb421 epitope was blocked by the protein serine
      phosphatase inhibitor calyculin A but was not blocked by the protein synthesis
      inhibitor cycloheximide, suggesting that serine 376 was dephosphorylated by
      protein serine phosphatase 1 or 2A acting on pre-existing p53 protein. The data
      suggest that dephosphorylation of serine 376 on constitutive nuclear p53 is a
      sensitive and early signaling event in the response of cells to DNA damage
      induced by ionizing radiation.

PMID- 19580480
TI  - Induction of adaptive response in human blood lymphocytes exposed to
      radiofrequency radiation.
AB  - The incidence of micronuclei was evaluated to assess the induction of an adaptive
      response to non-ionizing radiofrequency (RF) radiation in peripheral blood
      lymphocytes collected from five different human volunteers. After stimulation
      with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of
      900 MHz RF radiation used for mobile communications (at a peak specific
      absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic
      dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to
      examine the frequency of micronuclei in cytokinesis-blocked binucleated cells.
      Cells collected from four donors exhibited the induction of adaptive response
      (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had
      a significantly decreased incidence of micronuclei induced by the challenge dose
      of mitomycin C compared to those that were not pre-exposed to 900 MHz RF
      radiation. These preliminary results suggested that the adaptive response can be
      induced in cells exposed to non-ionizing radiation. A similar phenomenon has been
      reported in cells as well as in animals exposed to ionizing radiation in several
      earlier studies. However, induction of adaptive response was not observed in the
      remaining donor (i.e., non-responder). The incidence of micronuclei induced by
      the challenge dose of mitomycin C was not significantly different between the
      cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the
      overall data indicated the existence of heterogeneity in the induction of an
      adaptive response between individuals exposed to RF radiation and showed that the
      less time-consuming micronucleus assay can be used to determine whether an
      individual is a responder or non-responder.

PMID- 19580482
TI  - Dose response of gamma rays and iron nuclei for induction of chromosomal
      aberrations in normal and repair-deficient cell lines.
AB  - We studied the effects of DNA double-strand break (DSB) repair deficiencies on
      chromosomal aberration frequency using low doses (<1 Gy) of gamma rays and high
      energy iron ions (LET = 151 keV/microm). Chromosomal aberrations were measured
      using the fluorescence whole-chromosome painting technique. The cell lines
      included fibroblasts deficient in ATM (product of the gene that is mutated in
      ataxia telangiectasia patients) or NBS (product of the gene mutated in the
      Nijmegen breakage syndrome) and gliomablastoma cells proficient in or lacking DNA
      dependent protein kinase (DNA-PK) activity. The yields of both simple and complex
      chromosomal aberrations were increased in DSB repair-defective cells compared to
      normal cells; the increase was more than twofold higher for gamma rays compared
      to iron nuclei. For gamma-ray-induced aberrations, the ATM- and NBS-defective
      lines were found to have significantly larger quadratic components compared to
      normal fibroblasts for both simple and complex aberrations, while the linear dose
      response term was significantly higher only for the NBS cells. For simple and
      complex aberrations induced by iron nuclei, regression models preferred purely
      linear and quadratic dose responses, respectively, for each cell line studied.
      RBEs were reduced relative to normal cells for all of the DSB repair-defective
      lines, with the DNA-PK-deficient cells found to have RBEs near unity. The large
      increase in the quadratic dose-response terms in the DSB repair-deficient cell
      lines points to the importance of the functions of ATM and NBS in chromatin
      modifications to facilitate correct DSB repair and to minimize aberration
      formation. The differences found between AT and NBS cells at lower doses suggest
      important questions about the applicability of observations of radiation
      sensitivity at high doses to low-dose exposures.

PMID- 19580481
TI  - Human fibroblasts and 900 MHz radiofrequency radiation: evaluation of DNA damage
      after exposure and co-exposure to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)
      furanone (MX).
AB  - The aim of this study was to investigate DNA damage in human dermal fibroblasts
      from a healthy subject and from a subject affected by Turner's syndrome that were
      exposed for 24 h to radiofrequency (RF) radiation at 900 MHz. The RF-radiation
      exposure was carried out alone or in combination with 3-chloro-4-(dichloromethyl)
      5-hydroxy-2(5H)-furanone (MX), a well-known environmental mutagen and carcinogen
      produced during the chlorination of drinking water. Turner's syndrome fibroblasts
      were also exposed for a shorter time (1 h). A signal similar to that emitted by
      Global System for Mobile Communications (GSM) mobile phones was used at a
      specific absorption rate of 1 W/kg under strictly controlled conditions of
      temperature and dosimetry. To evaluate DNA damage after RF-radiation exposure
      alone, the alkaline comet assay and the cytokinesis-block micronucleus assay were
      used. In the combined-exposure experiments, MX was given at a concentration of 25
      microM for 1 h immediately after the RF-radiation exposure, and the effects were
      evaluated by the alkaline comet assay. The results revealed no genotoxic and
      cytotoxic effects from RF radiation alone in either cell line. As expected, MX
      treatment induced an increase in DNA migration in the comet assay, but no
      enhancement of the MX-induced DNA damage was observed in the cells exposed to RF
      radiation.

PMID- 19580483
TI  - Threshold-type dose response for induction of neoplastic transformation by 1
      GeV/nucleon iron ions.
AB  - Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses
      of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has
      been examined. The data indicate a threshold-type dose-response curve with no
      increase in transformation frequency until doses above 20 cGy. At doses <10 cGy,
      not all exposed cells receive a direct traversal of an iron-ion track core, but
      all exposed cells receive up to several mGy of low-LET radiation associated with
      the delta-ray penumbra. It is proposed that the threshold-type response seen is a
      consequence of an adaptive response associated with the delta-ray exposure. For
      comparison purposes, the dose response for (137)Cs gamma rays over the same dose
      range was examined using the same experimental procedure. As we have shown
      previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron
      ions were 1.5 to 1.7 times more biologically effective than the gamma radiation
      over the dose range examined.

PMID- 19580486
TI  - Propagation distance of the alpha-particle-induced bystander effect: the role of
      nuclear traversal and gap junction communication.
AB  - When cell populations are exposed to low-dose alpha-particle radiation, a
      significant fraction of the cells will not be traversed by a radiation track.
      However, stressful effects occur in both irradiated and bystander cells in the
      population. Characterizing these effects, and investigating their underlying
      mechanism(s), is critical to understanding human health risks associated with
      exposure to alpha particles. To this end, confluent normal human fibroblast
      cultures were grown on polyethylene terephthalate foil grafted to an ultrathin
      solid-state nuclear track detector and exposed under non-perturbing conditions to
      low-fluence alpha particles from a broadbeam irradiator. Irradiated and affected
      bystander cells were localized with micrometer precision. The stress-responsive
      protein p21(Waf1) (also known as CDKN1A) was induced in bystander cells within a
      100-microm radius from an irradiated cell. The mean propagation distance ranged
      from 20 to 40 microm around the intranuclear alpha-particle impact point, which
      corresponds to a set of approximately 30 cells. Nuclear traversal, induced DNA
      damage, and gap junction communication were critical contributors to propagation
      of this stressful effect. The strategy described here may be ideal to investigate
      the size of radiation-affected target and the relative contribution of different
      cellular organelles to bystander effects induced by energetic particles, which is
      relevant to radioprotection and cancer radiotherapy.

PMID- 19580487
TI  - Do radiation-induced bystander effects correlate to the intrinsic
      radiosensitivity of individuals and have clinical significance?
AB  - It is well known that patients can vary in their normal tissue response to
      radiotherapy, and this can be problematic. As a result, radiobiologists have been
      using in vitro models to assess variation in response and elucidate the genetic
      determinants of this variation. However, the clinical relevance of these models
      is currently unknown. In this study, blood samples from healthy controls (n = 20)
      and colorectal carcinoma patients (n = 60) were cultured in vitro to assess two
      radiobiological end points in parallel: intrinsic radiosensitivity assayed by
      chromosomal aberrations (G(2) scores) and radiation-induced bystander effects
      assayed by viability testing. Increased intrinsic radiosensitivity was observed
      in colorectal carcinoma donors (55%) compared to the healthy donors (5%) (P <
      0.005). Similarly, more pronounced radiation-induced bystander effects were
      observed in the colorectal carcinoma donors compared to the healthy donors after
      24 h exposure but not after 96 h exposure to donor irradiated cell conditioned
      medium (ICCM) (P < 0.05). All scores were tested for correlation with the age,
      sex and clinical stage of the colorectal carcinoma patients. The only
      statistically significant correlation was found in samples from severe Dukes D
      patients (P < 0.005), which had low/radioresistant G(2) scores. No correlation
      was found between radiation-induced intrinsic sensitivity and bystander effects,
      which suggests that they may have separate underlying molecular mechanisms, but
      they both show clinical relevance in individual patient samples.

PMID- 19580484
TI  - Expression of activated checkpoint kinase 2 and histone 2AX in exfoliative oral
      cells after exposure to ionizing radiation.
AB  - Gamma-H2AX (activated histone 2AX) and pChk2 (activated checkpoint kinase 2),
      which are DNA damage response molecules, are produced in irradiated cells and may
      be signature molecules of radiation exposure. We investigated their use as
      potential biomarkers to identify individuals exposed to ionizing radiation. We
      collected exfoliated oral epithelial cell samples from 100 healthy individuals
      undergoing routine dental radiographic examination (2.34 cGy) both before and
      after the radiograph using a non-invasive technique. The expression levels of
      pChk2 and gamma-H2AX in oral cells were assessed by immunohistochemical assay.
      Both biomarkers showed statistically significant increases in levels of
      expression after the radiation exposure (P < 0.001). This suggests that pChk2 and
      gamma-H2AX may serve as sensitive indicators of low-dose radiation exposure.

PMID- 19580488
TI  - No evidence for DNA and early cytogenetic damage in bystander cells after heavy
      ion microirradiation at two facilities.
AB  - The occurrence of bystander effects has challenged the evaluation of risk for
      heavy ions, mainly in the context of space exploration and the increasing
      application of carbon ions in radiotherapy. In the present study, we addressed
      whether heavy-ion-induced DNA and cytogenetic damage is detectable in bystander
      cells. The formation of gamma-H2AX foci, sister chromatid exchanges and
      micronuclei were used as markers of damage to DNA. Normal human fibroblasts were
      exposed to low fluences of carbon and uranium ions, and alternatively single
      cells were targeted with heavy ions using the GSI microbeam. We did not observe a
      significant increase in the bystander formation of gamma-H2AX foci, sister
      chromatid exchanges or micronuclei. In addition, we performed for the first time
      parallel experiments at two microbeam facilities (GSI, JAEA) using the same cell
      line, culture conditions and irradiation protocols. No significant enhancement of
      the micronucleus frequencies in bystander cells was detected after targeted
      carbon-ion irradiation, confirming the results. Details regarding the history,
      culture conditions or support of the cells might be affecting the detection of
      bystander effects. On the other hand, the potential X-ray- and heavy-ion-induced
      bystander effects investigated herein clearly do not exceed the experimental
      error and thus are either lacking or are less pronounced than the effects
      reported in the literature for similar end points after alpha-particle and X-ray
      exposure.

PMID- 19580489
TI  - Strategy for population triage based on dicentric analysis.
AB  - After large-scale accidental overexposure to ionizing radiation, a rapid triage
      of the exposed population can be performed by scoring dicentrics and ring
      chromosomes among 50 metaphases. This is rapid but is not accurate because the
      sensitivity is around 0.5 Gy. After the triage step, dose can be estimated by
      scoring 500 metaphases. This is lengthy but very accurate because the sensitivity
      is between 0.1 and 0.2 Gy. To improve the methodology, we propose the use of
      software for automatic dicentric scoring that was tested on victims of an
      accident in Dakar. Manual scoring of 50 metaphases was carried out, then manual
      scoring of 500 metaphases, and automatic scoring. Comparison between the dose
      classifications obtained with manual scoring on 50 metaphases and 500 metaphases
      showed 50% misclassification with the manual scoring on 50 metaphases. Comparison
      between the dose classifications obtained with the automatic scoring and manual
      scoring on 500 metaphases showed only 4.35% misclassification with the automatic
      scoring. The automatic scoring method is more accurate than the manual scoring on
      50 metaphases and can therefore be used for triage, and in place of the manual
      scoring on 500 metaphases method for individual dose estimation, because it is as
      accurate and much faster.

PMID- 19580490
TI  - Antibody-based screen for ionizing radiation-dependent changes in the Mammalian
      proteome for use in biodosimetry.
AB  - In an effort to identify proteomic changes that may be useful for radiation
      biodosimetry, human cells of hematological origin were treated with ionizing
      radiation or mock-irradiated and then harvested at different times after
      treatment. Protein lysates were generated from these cells and evaluated by
      Western blotting using a panel of 301 commercially available antibodies targeting
      161 unique proteins. From this screen, we identified 55 ionizing radiation
      responsive proteins, including 14 proteins not previously reported to be
      radiation-responsive at the protein level. The data from this large-scale screen
      have been assembled into a public website (
      http://labs.fhcrc.org/paulovich/biodose_index.html ) that may be of value to the
      radiation community both as a source of putative biomarkers for biodosimetry and
      also as a source of validation data on commercially available antibodies that
      detect radiation-responsive proteins. Using a panel of candidate radiation
      biomarkers in human cell lines, we demonstrate the feasibility of assembling a
      complementary panel of radiation-responsive proteins. Furthermore, we demonstrate
      the feasibility of using blood cell-based proteomic changes for biodosimetry by
      demonstrating detection of protein changes in circulating cells after total-body
      irradiation in a canine model.

PMID- 19580491
TI  - Cellular response to chemoradiotherapy, radiotherapy and chemotherapy in two
      colorectal cancer cell lines.
AB  - The cellular response to chemoradiotherapy was investigated in cells of the
      HCT116 (wild-type TP53) and HT29 (mutated TP53) human colorectal cancer cell
      lines to better understand how the chemotherapeutic agent 5-fluorouracil (5-FU)
      acts as a radiosensitizer in vitro and how it contributes to the well-documented
      greater efficacy of chemoradiotherapy compared to radiotherapy (or chemotherapy)
      alone. A bolus 5-FU treatment protocol that simulated actual clinical clearance
      kinetics was used with a radiation dose given within 90 min after drug addition.
      The involvements of key signaling pathways (DNA damage response, cell cycle
      progression, cell proliferation, cell death) in cell responses were investigated
      concurrently, allowing for direct correlations of numerous treatment response
      phenotypes. Early DNA damage response, substantial cell death, loss of
      clonogenicity, and senescence characterized both radiotherapy- and
      chemoradiotherapy-treated cultures but not chemotherapy-treated cultures. The
      largest G(2)/M arrests and strongest correlation of senescence with non
      clonogenicity were seen in radiotherapy- and chemoradiotherapy-treated HCT116
      cell cultures, suggesting that functional TP53 could play a role in
      maintaining/inducing these cellular phenotypes. Overall, chemoradiotherapy proved
      to be the most effective treatment modality since it resulted in the strongest
      growth inhibitions, largest G(2)/M arrests, largest fractions of senescent cells,
      and complete loss of clonogenicity in both cell lines.

PMID- 19580492
TI  - The impact of intracellular generation of nitric oxide on the radiation response
      of human tumor cells.
AB  - Nitric oxide (NO) is a potent radiosensitizer of hypoxic mammalian cells. There
      have been many reports demonstrating radiosensitization in vitro and in vivo by
      the use of NO donors to generate NO by chemical means or by producing agents that
      mimic the free radical mechanism(s) of NO for potentiating radiosensitivity.
      However, much of this work has been done without taking account of the endogenous
      NO that is generated in tumor cells by NO synthase (NOS) in vitro or in tumor
      cells and host cells in solid tumors in vivo. To evaluate the contribution of
      intracellular generated NO to cellular radiosensitivity, we exposed human HT1080
      and MDA231 tumor cells to a cytokine cocktail that results in an increase in
      cellular NOS expression to a level that is seen in many human solid tumors. We
      also carried out parallel studies to determine the radiosensitivity of HT1080 and
      MDA231 cells engineered to constitutively overexpress the iNOS gene. When cells
      are treated with cytokines under anoxic conditions (<0.01% O(2)), there is up to
      a 9-15-fold increase in NOS expression, but no detectable NO is generated (since
      O(2) is required for the generation of NO via the NOS-mediated conversion of
      arginine to citrulline). As a consequence, when these cells are irradiated under
      hypoxic conditions, no radiosensitization is observed. However, as the oxygen
      tension was increased, the amount of NO generated also increased, and we show
      that this NO then contributes to an overall increase in the radiosensitivity of
      cells. For example, at 1% O(2) in control HT1080 cells, with little measurable
      NOS activity, the dose of radiation required to reduce survival by 90% was 6 Gy
      compared to 10 Gy in anoxic conditions. After cytokine treatment, the level of NO
      generated at 1% O(2) was significantly increased and the dose of radiation needed
      for 90% cell killing was reduced further to 4 Gy. The presence of the NOS
      inhibitor N(G)-methyl-l-arginine (NMLA) shortly before and during irradiation
      ablated this increase in radiosensitivity, confirming that the effect was due to
      the generation of NO. We conclude that cytokine-mediated up-regulation of the NOS
      expression in tumor cells can produce sufficient NO to significantly increase the
      cytotoxic effect of radiation and that this is particularly apparent at
      intermediate oxygen concentrations.

PMID- 19580493
TI  - Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint
      activation in human pancreatic cancer cells.
AB  - We hypothesized that mitochondrial function regulates cell cycle checkpoint
      activation and radiosensitivity. Human pancreatic tumor cells (MiaPaCa-2, rho(+))
      were depleted of mitochondrial DNA (rho degrees ) by culturing cells in the
      presence of ethidium bromide. Depletion of mitochondrial DNA was verified by PCR
      amplification of total DNA using primer pairs specific for mitochondrial DNA.
      Loss of mitochondrial DNA decreased plating efficiency and the percentage of
      cells in S phase. Exponential cultures were irradiated with 2, 4 and 6 Gy (dose
      rate: 0.83 Gy/min) of ionizing radiation and harvested for determination of cell
      viability, growth and cell cycle phase distributions. Rho degrees cells were
      radioresistant compared to rho(+) cells, with a dose-modifying factor (DMF) of
      1.6. Although cell growth was significantly inhibited in irradiated rho(+) cells
      compared to unirradiated control cells, the inhibition in Rho degrees cells was
      minimal. In addition, mitochondrial DNA depletion suppressed radiation-induced
      G(2) checkpoint activation, which was accompanied by increases in both cyclin B1
      and CDK1. These results suggest that mitochondrial function may regulate cell
      cycle checkpoint activation and radiosensitivity in pancreatic cancer cells.

PMID- 19580494
TI  - Mitochondrial targeting of a catalase transgene product by plasmid liposomes
      increases radioresistance in vitro and in vivo.
AB  - To determine whether increased mitochondrially localized catalase was
      radioprotective, a human catalase transgene was cloned into a small pSVZeo
      plasmid and localized to the mitochondria of 32D cl 3 cells by adding the
      mitochondrial localization sequence of MnSOD (mt-catalase). The cell lines 32D
      Cat and 32D-mt-Cat had increased catalase biochemical activity as confirmed by
      Western blot analysis compared to the 32D cl 3 parent cells. The MnSOD
      overexpressing 32D cl 3 cell line, 2C6, had decreased baseline catalase activity
      that was increased in 2C6-Cat and 2C6-mt-Cat subclonal cell lines. 32D-mt-Cat
      cells were more radioresistant than 32D-Cat cells, but both were radioresistant
      relative to 32D cl 3 cells. 2C6-mt-Cat cells but not 2C6-Cat cells were
      radioresistant compared to 2C6 cells. Intratracheal injection of the mt-catalase
      plasmid liposome complex (mt-Cat-PL) but not the catalase-plasmid liposome
      complex (Cat-PL) increased the resistance of C57BL/6NHsd female mice to 20 Gy
      thoracic irradiation compared to MnSOD-plasmid liposomes. Thus mitochondrially
      targeted overexpression of the catalase transgene is radioprotective in vitro and
      in vivo.

PMID- 19580496
TI  - Alterations in daily sequencing of axitinib and fractionated radiotherapy do not
      affect tumor growth inhibition or pathophysiological response.
AB  - A variety of antiangiogenic strategies have proven effective in preclinical tumor
      models, either as single agents or in combination with radiation. Clinical gains
      have been relatively modest, however, and questions remain regarding optimal
      scheduling. The objectives of the current work were to evaluate whether the
      sequencing of acute treatment critically affects tumor pathophysiological and
      therapeutic response. Axitinib (Pfizer Global Research & Development), an
      inhibitor that predominantly targets vascular endothelial growth factor
      receptors, was administered either before or after each daily radiation fraction
      in two human prostate xenograft tumor models. Tumors were frozen at sequential
      times to monitor changes in (1) vascular spacing, (2) pericyte and basement
      membrane coverage, and (3) hypoxia. Although similar reductions in blood vessel
      counts were observed with each tumor model, tumor vasculature was not
      functionally normalized. Instead, tumor hypoxia increased, accompanied by a
      progressive dissociation of pericytes and basement membranes. Ultimately, tumor
      growth inhibition was found to be equivalent for each of the combination
      schedules. These studies illustrate a clear advantage to combining axitinib with
      fractionated therapy but argue against an acute radiosensitization or
      radioprotection of either the tumor cells or tumor vasculature. Instead, post-
      and preirradiation daily drug administration serve equally well in supplementing
      the response to radiotherapy.

PMID- 19580495
TI  - gamma-Tocotrienol ameliorates intestinal radiation injury and reduces vascular
      oxidative stress after total-body irradiation by an HMG-CoA reductase-dependent
      mechanism.
AB  - Analogs of vitamin E (tocols) are under development as radioprophylactic agents
      because of their high efficacy and lack of toxicity. Gamma-tocotrienol (GT3) is
      of particular interest because, in addition to being an antioxidant, it also
      inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and
      accumulates to greater extent in endothelial cells than other tocols. We
      addressed in vivo whether HMG-CoA reductase inhibition contributes to the
      radioprotection conferred by GT3. Groups of mice were treated with vehicle,
      mevalonate (the product of the reaction catalyzed by HMG-CoA reductase), GT3
      alone or GT3 in combination with mevalonate. Lethality and standard parameters of
      injury to the hematopoietic, intestinal and vascular/endothelial systems were
      assessed after exposure to total-body irradiation. GT3 improved postirradiation
      survival and decreased radiation-induced vascular oxidative stress, an effect
      that was reversible by mevalonate. GT3 also enhanced hematopoietic recovery,
      reduced intestinal radiation injury, and accelerated the recovery of soluble
      markers of endothelial function. These parameters were not reversed by mevalonate
      co-administration. Our data confirm GT3's radioprophylactic properties against
      hematopoietic injury and, for the first time, demonstrate benefits in terms of
      protection against gastrointestinal and vascular injury. The radioprotective
      efficacy of GT3 against vascular injury is related to its properties as an HMG
      CoA reductase inhibitor.

PMID- 19580497
TI  - Radiofrequency-radiation exposure does not induce detectable leakage of albumin
      across the blood-brain barrier.
AB  - The blood-brain barrier (BBB) consists of tight junctions between the endothelial
      cells that line the capillaries in the central nervous system. This structure
      protects the brain, and neurological damage could occur if it is compromised.
      Several publications by researchers at Lund University have reported alterations
      in the BBB after exposure to low-power 915 MHz energy. These publications
      increased the level of concern regarding the safety of wireless communication
      devices such as mobile phones. We performed a confirmation study designed to
      determine whether the BBB is altered in rats exposed in a transverse
      electromagnetic (TEM) transmission line cell to 915 MHz energy at parameters
      similar to those in the Lund University studies. Unanesthetized rats were exposed
      for 30 min to either continuous-wave or modulated (16 or 217 Hz) 915 MHz energy
      at power levels resulting in whole-body specific absorption rates (SARs) of
      0.0018-20 W/kg. Albumin immunohistochemistry was performed on perfused brain
      tissue sections to determine the integrity of the BBB. Chi-square analysis
      revealed no significant increase in albumin extravasation in any of the exposed
      animals compared to the sham-exposed or home cage control animals.

PMID- 19580498
TI  - Radiolytic yield of cardiolipin peroxidation by gamma rays in large unilamellar
      vesicles of phosphatidylcholine.
AB  - Large unilamellar vesicles of 1-hexanoyl-2-(9Z-12Z-octadecadienoyl)-sn-glycero-3
      phosphocholine (PLPC) have been used as model membrane to investigate the effect
      of increasing amount of cardiolipin (1',3'-bis-[1,2-Di-(9Z-12Z-octadecadienoyl)
      sn-glycero-3-phospho]-sn-glycerol, CL) on the peroxidizability of the lipid
      phase. Hydroxyl radicals generated by gamma radiolysis of water initiated the
      lipid peroxidation. Both peroxidation products (conjugated dienes and
      hydroperoxides of PLPC, mono- and dihydroperoxides of CL) and disappearance of CL
      and PLPC were assessed as a function of the radiation dose (25 to 400 Gy, I = 10
      Gy min(-1)). Our results show that the addition of 5% to 15% CL to large
      unilamellar vesicles (concentration ratio) produces almost complete inhibition of
      PLPC peroxidation. Thus, for 15% CL (known to be the proportion of CL in the
      inner mitochondrial membrane), the radiolytic yield of formation of PLPC
      hydroperoxides is reduced to zero, whereas it is equal to (3.1 +/- 0.2) x 10(-7)
      mol J(-1) for CL hydroperoxides, showing the importance of the targeted CL. For
      this concentration ratio (CL/ PLPC 15%), we have established the balance equation
      between the consumption of CL [G(-CL) = (2.8 +/- 0.1) x 10(-7) mol J(-1)] and the
      formation of CL hydroperoxides [G(CLOOH(T)) = (3.1 +/- 0.2) x 10(-7) mol J(-1)].
      In addition, the radiolytic yields of disappearance of PLPC and CL have been
      determined [(1.5 +/- 0.1) x 10(-7) mol J(-1) and (2.8 +/- 0.1) x 10(-7) mol J(
      1), respectively], their sum [(4.3 +/- 0.2) x 10(-7) mol J(-1)] being higher than
      G(HO.) (2.8 x 10(-7) mol J(-1)). However, there is no balance between the
      radiolytic yield of formation of PLPC hydroperoxides [G (PCOOH(T)) approximately
      0] and the yield of disappearance of PLPC [(1.5 +/- 0.1) x 10(-7) mol J(-1)],
      likely because lipid fragments (not measured in this work) could be generated
      from HO(.) reaction on the polar head of PLPC. These results have been
      interpreted by assuming that the hydroxyl radicals attack in competition both
      lipid targets, i.e. PLPC and CL, with a higher sensitivity to CL oxidation. It
      can be concluded that a little amount of CL (10-15% CL/ PLPC concentration ratio)
      may exert a strong protective effect against the HO(.)-induced peroxidation of
      PLPC.

PMID- 19580502
TI  - Radiation cataractogenesis: a review of recent studies.
AB  - The lens of the eye is recognized as one of the most radiosensitive tissues in
      the human body, and it is known that cataracts can be induced by acute doses of
      less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of protracted
      radiation. Although much work has been carried out in this area, the exact
      mechanisms of radiation cataractogenesis are still not fully understood. In
      particular, the question of the threshold dose for cataract development is not
      resolved. Cataracts have been classified as a deterministic effect of radiation
      exposure with a threshold of approximately 2 Gy. Here we review the combined
      results of recent mechanistic and human studies regarding induction of cataracts
      by ionizing radiation. These studies indicate that the threshold for cataract
      development is certainly less than was previously estimated, of the order of 0.5
      Gy, or that radiation cataractogenesis may in fact be more accurately described
      by a linear, no-threshold model.

PMID- 19580503
TI  - NASA study of cataract in astronauts (NASCA). Report 1: Cross-sectional study of
      the relationship of exposure to space radiation and risk of lens opacity.
AB  - The NASA Study of Cataract in Astronauts (NASCA) is a 5-year longitudinal study
      of the effect of space radiation exposure on the severity/progression of nuclear,
      cortical and posterior subcapsular (PSC) lens opacities. Here we report on
      baseline data that will be used over the course of the longitudinal study.
      Participants include 171 consenting astronauts who flew at least one mission in
      space and a comparison group made up of three components: (a) 53 astronauts who
      had not flown in space, (b) 95 military aircrew personnel, and (c) 99 non-aircrew
      ground-based comparison subjects. Continuous measures of nuclear, cortical and
      PSC lens opacities were derived from Nidek EAS 1000 digitized images. Age,
      demographics, general health, nutritional intake and solar ocular exposure were
      measured at baseline. Astronauts who flew at least one mission were matched to
      comparison subjects using propensity scores based on demographic characteristics
      and medical history stratified by gender and smoking (ever/never). The cross
      sectional data for matched subjects were analyzed by fitting customized non
      normal regression models to examine the effect of space radiation on each measure
      of opacity. The variability and median of cortical cataracts were significantly
      higher for exposed astronauts than for nonexposed astronauts and comparison
      subjects with similar ages (P=0.015). Galactic cosmic space radiation (GCR) may
      be linked to increased PSC area (P=0.056) and the number of PSC centers
      (P=0.095). Within the astronaut group, PSC size was greater in subjects with
      higher space radiation doses (P=0.016). No association was found between space
      radiation and nuclear cataracts. Cross-sectional data analysis revealed a small
      deleterious effect of space radiation for cortical cataracts and possibly for PSC
      cataracts. These results suggest increased cataract risks at smaller radiation
      doses than have been reported previously.

PMID- 19580504
TI  - Musculoskeletal changes in mice from 20-50 cGy of simulated galactic cosmic rays.
AB  - On a mission to Mars, astronauts will be exposed to a complex mix of radiation
      from galactic cosmic rays. We have demonstrated a loss of bone mass from exposure
      to types of radiation relevant to space flight at doses of 1 and 2 Gy. The
      effects of space radiation on skeletal muscle, however, have not been
      investigated. To evaluate the effect of simulated galactic cosmic radiation on
      muscle fiber area and bone volume, we examined mice from a study in which brains
      were exposed to collimated iron-ion radiation. The collimator transmitted a
      complex mix of charged secondary particles to bone and muscle tissue that
      represented a low-fidelity simulation of the space radiation environment.
      Measured radiation doses of uncollimated secondary particles were 0.47 Gy at the
      proximal humerus, 0.24-0.31 Gy at the midbelly of the triceps brachii, and 0.18
      Gy at the proximal tibia. Compared to nonirradiated controls, the proximal
      humerus of irradiated mice had a lower trabecular bone volume fraction, lower
      trabecular thickness, greater cortical porosity, and lower polar moment of
      inertia. The tibia showed no differences in any bone parameter. The triceps
      brachii of irradiated mice had fewer small-diameter fibers and more fibers
      containing central nuclei. These results demonstrate a negative effect on the
      skeletal muscle and bone systems of simulated galactic cosmic rays at a dose and
      LET range relevant to a Mars exploration mission. The presence of evidence of
      muscle remodeling highlights the need for further study.

PMID- 19580505
TI  - Response of extracellular matrix regulators in mouse lung after exposure to
      photons, protons and simulated solar particle event protons.
AB  - This study compared the effects of photons (gamma rays), protons and simulated
      solar particle event protons (sSPE) on the expression of profibrotic
      factors/extracellular matrix (ECM) regulators in lung tissue after whole-body
      irradiation. TGF-beta1, matrix metalloproteinase 2 and 9 (MMP-2, -9), and tissue
      inhibitor of metalloproteinase 1 and 2 (TIMP-1, -2) were assessed on days 4 and
      21 in lungs from C57BL/6 mice exposed to 0 Gy or 2 Gy photons (0.7 Gy/min),
      protons (0.9 Gy/min) and sSPE (0.056 Gy/h). RT-PCR, histological and
      immunohistochemical techniques were used. The most striking changes included (1)
      up-regulation of TGF-beta1 by photons and sSPE, but not protons, at both times,
      (2) MMP-2 enhancement by photons and sSPEs, (3) TIMP-1 up-regulation by photons
      at both times, and (4) more collagen accumulation after exposure to either
      photons or sSPE than after exposure to protons. The findings demonstrate that
      expression of important ECM regulators was highly dependent upon the radiation
      regimen as well as the time after exposure. The data further suggest that
      irradiation during an SPE may increase an astronaut's risk for pulmonary
      complications. The greater perturbations after photon exposure compared to proton
      exposure have clinical implications and warrant further investigation.

PMID- 19580507
TI  - Comparison of expression profiles of several fibroblast growth factor receptors
      in the mouse jejunum: suggestive evidence for a differential radioprotective
      effect among major FGF family members and the potency of FGF1.
AB  - Several members of the fibroblast growth factor (FGF) family have the potential
      to protect the intestine against the side effects of radiation therapy. FGF1 is
      capable of signaling through all subtypes of FGF receptors (FGFRs), whereas FGF7
      and FGF10 activate only the epithelial-specific subtype, FGFR2IIIb (FGFR2b). The
      present study compared the protective activity of FGF1, FGF7 and FGF10 and
      examined the profiles of FGFR expression in the jejunum of BALB/c mice given
      total-body irradiation (TBI) with gamma rays. TBI caused drastic increases in
      FGFR1-4 transcript levels in the jejunum. However, FGFR2b protein temporarily
      decreased at 12 and 24 h after irradiation. FGF1 pretreatment minimized the
      number of apoptotic cells in jejunal crypts at 16 and 24 h after irradiation and
      increased crypt survival most effectively. In addition, pretreatment with FGF7 or
      FGF10 decreased FGFR1 transcript levels. The greater effectiveness of FGF1 to
      enhance crypt survival was also observed even when each FGF was administered 1 h
      after irradiation. These findings indicate that FGF1 is more potent than FGF7 or
      FGF10 for protection of the intestine against radiation exposure and suggest that
      the profiles of FGFR expression in the intestine favor the FGF1 signaling pathway
      before and during the initial period after irradiation.

PMID- 19580506
TI  - Radiation metabolomics. 2. Dose- and time-dependent urinary excretion of
      deaminated purines and pyrimidines after sublethal gamma-radiation exposure in
      mice.
AB  - Gamma-radiation exposure of humans is a major public health concern as the threat
      of terrorism and potential hostile use of radiological devices increases
      worldwide. We report here the effects of sublethal gamma-radiation exposure on
      the mouse urinary metabolome determined using ultra-performance liquid
      chromatography-coupled time-of-flight mass spectrometry-based metabolomics. Five
      urinary biomarkers of sublethal radiation exposure that were statistically
      significantly elevated during the first 24 h after exposure to doses ranging from
      1 to 3 Gy were unequivocally identified by tandem mass spectrometry. These are
      deaminated purine and pyrimidine derivatives, namely, thymidine, 2'-deoxyuridine,
      2'-deoxyxanthosine, xanthine and xanthosine. Furthermore, the aminopyrimidine 2'
      deoxycytidine appeared to display reduced urinary excretion at 2 and 3 Gy. The
      elevated biomarkers displayed a time-dependent excretion, peaking in urine at 8
      12 h but returning to baseline by 36 h after exposure. It is proposed that 2'
      deoxyuridine and 2'-deoxyxanthosine arise as a result of gamma irradiation by
      nitrosative deamination of 2'-deoxycytidine and 2'-deoxyguanosine, respectively,
      and that this further leads to increased synthesis of thymidine, xanthine and
      xanthosine. The urinary excretion of deaminated purines and pyrimidines, at the
      expense of aminopurines and aminopyrimidines, appears to form the core of the
      urinary radiation metabolomic signature of mice exposed to sublethal doses of
      ionizing radiation.

PMID- 19580508
TI  - Effects of 915 MHz electromagnetic-field radiation in TEM cell on the blood-brain
      barrier and neurons in the rat brain.
AB  - The aim of this study was to determine whether albumin leakage and dark neurons
      were present in rat brains 14 and 50 days after a single 2-h exposure to a 915
      MHz electromagnetic field, as reported by Salford et al. (Environ. Health
      Perspect. 111, 881-883, 203). Sixty-four male F344 rats (12 weeks old) were
      exposed to a 915 MHz electromagnetic field at whole-body average specific
      absorption rates of 0, 0.02, 0.2 and 2.0 W/kg in TEM cells for 2 h, following the
      protocol reported by Salford et al. The brains were examined histologically and
      immunohistochemically. No albumin immunoreactivity was observed in the exposed
      groups. In addition, dark neurons, assessed using hematoxylin and eosin staining,
      were rarely present, with no statistically significant difference between exposed
      and sham-exposed animals. This study thus failed to confirm the results of
      Salford et al.

PMID- 19580511
TI  - Regulation of the low-dose radiation paracrine-specific anchorage-independent
      growth response by annexin A2.
AB  - Here we identify the release of annexin A2 into the culture medium in response to
      low-dose X-radiation exposure and establish functional linkages to an established
      paracrine factor-mediated anchorage-independent growth response. Using a standard
      bicameral coculture model, we demonstrate that annexin A2 is secreted into the
      medium by irradiated cells (seeded in upper chamber) and is capable of binding to
      nonirradiated neighboring cells (seeded in lower chamber). The paracrine factor
      mediated anchorage-independent growth response to low-dose X irradiation is
      reduced when irradiated annexin A2-silenced (shRNA) JB6 cells are co-cultured
      with nonirradiated cells relative to co-culture with irradiated annexin A2
      competent vector control cells. Consistent with this observation, purified bovine
      annexin A2 tetramer induces anchorage-independent growth. These observations
      suggest that annexin A2 regulates, in part, the radiation paracrine factor
      specific anchorage-independent growth response in JB6 cells.

PMID- 19580509
TI  - Bystander effects induced by diffusing mediators after photodynamic stress.
AB  - The bystander effect, whereby cells that are not traversed by ionizing radiation
      exhibit various responses when in proximity to irradiated cells, is well
      documented in the field of radiation biology, Here we demonstrate that
      considerable bystander responses are also observed after photodynamic stress
      using the membrane-localizing dye deuteroporphyrin (DP). Using cells of a WTK1
      human lymphoblastoid cell line in suspension and a transwell insert system that
      precludes contact between targeted and bystander cells, we have shown that the
      bystander signaling is mediated by diffusing species. The extranuclear
      localization of the photosensitizer used suggests that primary DNA damage is not
      the trigger for initiating these bystander responses, which include elevated
      oxidative stress, DNA damage (micronucleus formation), mutagenesis and decreased
      clonogenic survival. In addition, oxidative stress in the bystander population
      was reduced by the presence of the membrane antioxidant vitamin E in the targeted
      cells, suggesting that lipid peroxidation may play a key role in mediating these
      bystander effects. The fluence responses for these bystander effects are non
      linear, with larger effects seen at lower fluences and toxicity to the target
      cell population. Hence, when considering outcomes of photodynamic action in cells
      and tissue, bystander effects may be significant, especially at sublethal
      fluences.

PMID- 19580510
TI  - Differential gene expression in primary human skin keratinocytes and fibroblasts
      in response to ionizing radiation.
AB  - Although skin is usually exposed during human exposures to ionizing radiation,
      there have been no thorough examinations of the transcriptional response of skin
      fibroblasts and keratinocytes to radiation. The transcriptional response of
      quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy
      and collected 4 h after treatment was examined. RNA was isolated and examined by
      microarray analysis for changes in the levels of gene expression. Exposure to
      ionizing radiation altered the expression of 279 genes across both cell types.
      Changes in RNA expression could be arranged into three main categories: (1)
      changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but
      not in keratinocytes, and (3) changes in both. All of these changes were
      primarily of p53 target genes. Similar radiation-induced changes were induced in
      immortalized fibroblasts or keratinocytes. In separate experiments, protein was
      collected and analyzed by Western blotting for expression of proteins observed in
      microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and
      Western blot analysis experiments validated these transcription changes. Our
      results are consistent with changes in the expression of p53 target genes as
      indicating the magnitude of cell responses to ionizing radiation.

PMID- 19580512
TI  - Dynamics of micronuclei in rat skin fibroblasts after X irradiation.
AB  - In a previous study, we demonstrated DNA damage, expressed as micronuclei, in
      binucleate dermal fibroblasts obtained from human skin 2-9 weeks after
      fractionated radiotherapy. Here we assessed micronuclei in X-irradiated skin
      fibroblasts from 9-14-week-old female Lewis rats as a function of time after a
      single dose of radiation to determine the lifetime of such damage in the skin.
      After irradiation with 5, 10, 15 and 18 Gy, formation of micronuclei at 1 day or
      2 months postirradiation increased up to about 10 Gy, with evidence for a plateau
      at higher doses. The time course of micronuclei present in the skin fibroblasts
      demonstrated a plateau region (approximately 20 days after 18 Gy and about 2
      months after 10 Gy) before the number of micronuclei started to decline. Residual
      micronuclei were observed for more than 1 year after irradiation.
      Monomicronucleated cells predominated in fibroblasts from nonirradiated skin,
      whereas in fibroblasts from irradiated skin, multimicronucleated cells
      predominated and persisted (together with monomicronucleated cells) in the
      residual levels of damage at late times. The results suggest that DNA damage in
      dermal fibroblasts can be assayed by the micronucleus assay in samples from
      irradiated skin up to 1 month after irradiation for doses up to at least 10 Gy.
      Further studies are needed to define the dose-response relationship in detail.

PMID- 19580514
TI  - Kinetic features of the radical species produced in gamma-irradiated dl-tartaric
      acid and the dosimetric potential of this acid.
AB  - The room-temperature and high-temperature kinetic features of the radical species
      produced in solid dl-tartaric acid (dl-TA) gamma-irradiated at room temperature
      and the dosimetric potential of this acid were investigated in a detailed ESR
      study. Irradiated dl-TA presents an ESR spectrum with many unresolved resonance
      lines even at the lowest radiation dose applied (100 Gy). The evolution of the
      signal intensities associated with induced radical species with microwave power,
      applied dose and temperature was followed. Three groups of resonance intensities
      originating from three different radicals exhibiting different spectroscopic
      features, stabilities at room and high temperatures, and radiation yields were
      found to take part in the formation of experimental ESR spectrum. These three
      species were calculated to exhibit spectroscopic features similar to those
      already reported for X- or gamma-irradiated deuterated single crystals of dl-TA
      and assigned as I, II and III. The same radical notation was adopted in the
      present work, and the intensities related to these species were denoted with the
      names of their corresponding species. Species III, which had the lowest radiation
      yield and the lowest stability, was observed as a species of four resonance
      lines. The two inner constituents of these four lines were partially obscured by
      the two central doublets originating from species I and II. The latter were
      relatively stable and had activation energies around 35 kJ/mol. The percentage
      concentrations of the involved species were estimated by comparing experimental
      and calculated spectra. The reasonably high radical yields of the dl-TA in the
      dose range of interest, the fairly good stabilities of the species produced (I
      and II) at room temperature, and the almost linear features of the constructed
      dose-response curves led us to conclude that the intensities associated with the
      stable species (I and II) could be used to estimate the applied dose in the dose
      range of 100 Gy-34 kGy with fairly good accuracy and that dl-TA could be a good
      candidate for exploring low radiation dose measurements by ESR dosimetry.

PMID- 19580513
TI  - Gold nanoparticles enhance DNA damage induced by anti-cancer drugs and radiation.
AB  - The chemotherapeutic agent cisplatin was chemically linked to pGEM-3Zf(-) plasmid
      DNA to produce a cisplatin-DNA complex, Gold nanoparticles, which bind
      electrostatically to pure DNA, could also be added to this complex. Dry films of
      pure plasmid DNA and DNA-cisplatin, DNA-gold nanoparticles and DNA-cisplatin-gold
      nanoparticles complexes were bombarded by 60 keV electrons. The yields of single-
      and double-strand breaks were measured as a function of exposure by
      electrophoresis. From a comparison of such yields from the different type of
      films, we found that the binding of only one gold nanoparticle to a plasmid
      cisplatin complex containing 3197 base pairs increases by a factor of 3 the
      efficiency of the chemotherapeutic agent cisplatin to produce double-strand
      breaks in irradiated DNA. Furthermore, adding two cisplatin molecules and one
      gold nanoparticle to DNA enhances radiation-induced DSBs by a factor of 7.5. A
      number of phenomena could contribute to this huge enhancement, including the
      higher density of low-energy electrons and reactive species around the gold
      nanoparticles and the weakening of bonds adjacent to cisplatin in the DNA
      backbone. The addition of gold nanoparticles to cisplatin and other platinum
      agents may therefore provide interesting avenues of research to improve the
      treatment of cancer by concomitant chemoradiation.

PMID- 19580515
TI  - Effect of gender on radiation-induced cataractogenesis.
AB  - Radiation cataractogenesis is an important consideration for radiotherapy
      patients and for astronauts. Data in the literature suggest that gender and/or
      estrogen may play a role in the incidence of age-related cataracts. However, few
      data exist on the effect of gender on radiation-induced cataractogenesis. We
      compared the incidence and rate of progression of cataracts induced by ionizing
      radiation in male and female Sprague-Dawley rats. Male rats were implanted with
      either an empty silastic capsule or a capsule containing 17-beta-estradiol. Ovary
      intact female rats were implanted with empty capsules. All rats received a single
      dose of 10 Gy (60Co gamma rays) to the right eye only. Lens opacification was
      measured at 2-4-week intervals with a slit lamp. The incidence of radiation
      induced cataracts was significantly increased in male rats compared to female
      rats (P=0.034). There was no difference in the rate of cataract progression
      between the three groups. Our data suggest there is a gender-related difference
      in radiation-induced cataractogenesis, but the increased incidence of radiation
      cataractogenesis in male rats compared to female rats cannot be attributed to
      estrogen levels, since there was no difference in cataract incidence between male
      rats implanted with empty capsules and those implanted with capsules containing
      17-beta-estradiol.

PMID- 19580516
TI  - Low dose radiation epidemiology: what can it tell us?

PMID- 19580518
TI  - Maximum similarity: a new formulation of phylogenetic reconstruction.
AB  - We present a new formulation of phylogenetic reconstruction named maximum
      similarity. We describe basic algorithms based on the maximum similarity
      objective for computing distances between subtrees and for combining two
      subtrees. We present distance methods for constructing an initial tree and
      updating the initial tree by incorporating those basic algorithms into the
      Neighbor Joining (NJ) method and the Nearest-Neighbor Interchange (NNI) framework
      of the FastME program. The new distance methods have been implemented as a
      computer program named MS. The time requirement of the MS program is about five
      times the cost of computing observed sequence distances. The MS program was
      compared by simulation with four existing programs: NJ, FastME, STC, and
      Weighbor. Experimental results show that incorporating the maximum similarity
      objective into existing methods leads to improvements both in topology and in
      branch length.

PMID- 19580519
TI  - Parametric complexity of sequence assembly: theory and applications to next
      generation sequencing.
AB  - In recent years, a flurry of new DNA sequencing technologies have altered the
      landscape of genomics, providing a vast amount of sequence information at a
      fraction of the costs that were previously feasible. The task of assembling these
      sequences into a genome has, however, still remained an algorithmic challenge
      that is in practice answered by heuristic solutions. In order to design better
      assembly algorithms and exploit the characteristics of sequence data from new
      technologies, we need an improved understanding of the parametric complexity of
      the assembly problem. In this article, we provide a first theoretical study in
      this direction, exploring the connections between repeat complexity, read
      lengths, overlap lengths and coverage in determining the "hard" instances of the
      assembly problem. Our work suggests at least two ways in which existing
      assemblers can be extended in a rigorous fashion, in addition to delineating
      directions for future theoretical investigations.

PMID- 19580520
TI  - Maximal information transfer and behavior diversity in Random Threshold Networks.
AB  - Random Threshold Networks (RTNs) are an idealized model of diluted, non-symmetric
      spin glasses, neural networks or gene regulatory networks. RTNs also serve as an
      interesting general example of any coordinated causal system. Here we study the
      conditions for maximal information transfer and behavior diversity in RTNs. These
      conditions are likely to play a major role in physical and biological systems,
      perhaps serving as important selective traits in biological systems. We show that
      the pairwise mutual information is maximized in dynamically critical networks.
      Also, we show that the correlated behavior diversity is maximized for slightly
      chaotic networks, close to the critical region. Importantly, critical networks
      maximize coordinated, diverse dynamical behavior across the network and across
      time: the information transmission between source and receiver nodes and the
      diversity of dynamical behaviors, when measured with a time delay between the
      source and receiver, are maximized for critical networks.

PMID- 19580522
TI  - Simultaneous class discovery and classification of microarray data using spectral
      analysis.
AB  - Classification methods are commonly divided into two categories: unsupervised and
      supervised. Unsupervised methods have the ability to discover new classes by
      grouping data into clusters or tree structures without using the class labels,
      but they carry the risk of producing noninterpretable results. On the other hand,
      supervised methods always find decision rules that discriminate samples with
      different class labels. However, the class label information plays such an
      important role that it confines supervised methods by defining the possible
      classes. Consequently, supervised methods do not have the ability to discover new
      classes. To overcome the limitations of unsupervised and supervised methods, we
      propose a new method, which utilizes the class labels to a less important role so
      as to perform class discovery and classification simultaneously. The proposed
      method is called SPACC (SPectral Analysis for Class discovery and
      Classification). In SPACC, the training samples are nodes of an undirected
      weighted network. Using spectral analysis, SPACC iteratively partitions the
      network into a top-down binary tree. Each partitioning step is unsupervised, and
      the class labels are only used to define the stopping criterion. When the
      partitioning ends, the training samples have been divided into several subsets,
      each corresponding to one class label. Because multiple subsets can correspond to
      the same class label, SPACC may identify biologically meaningful subclasses, and
      minimize the impact of outliers and mislabeled data. We demonstrate the
      effectiveness of SPACC for class discovery and classification on microarray data
      of lymphomas and leukemias. SPACC software is available at
      http://icbp.stanford.edu/software/SPACC/.

PMID- 19580523
TI  - Dynamic programming algorithms and grammatical modeling for protein beta-sheet
      prediction.
AB  - Protein structure prediction is one major task in computational biology, and
      various methods have been proposed for secondary structure prediction. In
      particular, it is a challenge to predict beta-sheet structures since they range
      over several discontinuous regions in an amino acid sequence. In this article, we
      propose dynamic programming algorithms for several kinds of antiparallel beta
      sheets, where the proposed approach can be extended for more general classes of
      beta-sheets. Experimental results for real data show that our prediction
      algorithms have good performance in accuracy. We also show a relation between the
      proposed algorithms and an existing grammar-based method, and present another
      grammatical modeling. Furthermore, we prove that prediction of planar beta-sheet
      structures is NP-hard.

PMID- 19580524
TI  - Estimation of gene induction enables a relevance-based ranking of gene sets.
AB  - In order to handle and interpret the vast amounts of data produced by microarray
      experiments, the analysis of sets of genes with a common biological functionality
      has been shown to be advantageous compared to single gene analyses. Some
      statistical methods have been proposed to analyse the differential gene
      expression of gene sets in microarray experiments. However, most of these methods
      either require threshhold values to be chosen for the analysis, or they need some
      reference set for the determination of significance. We present a method that
      estimates the number of differentially expressed genes in a gene set without
      requiring a threshold value for significance of genes. The method is self
      contained (i.e., it does not require a reference set for comparison). In contrast
      to other methods which are focused on significance, our approach emphasizes the
      relevance of the regulation of gene sets. The presented method measures the
      degree of regulation of a gene set and is a useful tool to compare the induction
      of different gene sets and place the results of microarray experiments into the
      biological context. An R-package is available.

PMID- 19580525
TI  - New treatments and outcomes in peritoneal carcinomatosis.

PMID- 19580521
TI  - Stochastic modeling and simulation of the p53-MDM2/MDMX loop.
AB  - The p53 gene is crucial for effective tumor suppression in humans as supported by
      its universal inactivation in cancer cells either through mutations affecting the
      p53 locus directly or through aberration of its normal regulation. The p53 tumor
      repressor is regulated through a negative feedback loop involving its
      transcriptional target MDM2. MDMX is also an essential negative regulator of p53.
      Several computational models have been proposed to simulate the dynamics of the
      p53-MDM2 loop, but they do not include MDMX, only account for some basic
      interactions between p53 and MDM2 and cannot capture the intrinsic noise in the
      loop. In this article, we present a comprehensive model for the p53-MDM2/MDMX
      loop that accounts for most known interactions among p53, MDM2 and MDMX. Our
      model is characterized by a set of molecular reactions, which enables us to
      employ stochastic simulation to investigate the dynamics of the loop. In
      agreement with experiments, our results show that p53 and MDM2 undergo
      oscillations after DNA damage in the presence of noise, and the variation in
      oscillation amplitudes is much higher than that in oscillation periods. Our
      simulations predict that intrinsic noise contributes to 60%-70% of the total
      variation in oscillation amplitudes and periods. The protein levels of p53, MDM2,
      and MDMX after treatment with Nutlin in our simulations are also consistent with
      experimental results. Our simulation results further predict that p53 levels
      increase dramatically after MDM2 is knocked out, but increase with a much less
      amount after MDMX is knocked out. This may partially explain why MDM2-null and
      MDMX-null mouse embryos die in different developmental stages. Our stochastic
      model and simulation provide insights into the variability of the behavior of the
      p53 pathway and can be used to predict the dynamics of the pathway after certain
      interventions.

PMID- 19580526
TI  - Non-invasive prenatal diagnosis - toward a new horizon.

PMID- 19580527
TI  - A conversation about health care safety and quality.

PMID- 19580528
TI  - Acute medical admissions in our hospitals: getting it right.

PMID- 19580529
TI  - Black Saturday: the immediate impact of the February 2009 bushfires in Victoria,
      Australia.
AB  - OBJECTIVE: To examine the response of the Victorian State Trauma System to the
      February 2009 bushfires. DESIGN AND SETTING: A retrospective review of the
      strategic response required to treat patients with bushfire-related injury in the
      first 72 hours of the Victorian bushfires that began on 7 February 2009.
      Emergency department (ED) presentations and initial management of patients
      presenting to the state's adult burns centre (The Alfred Hospital [The Alfred])
      were analysed, as well as injuries and deaths associated with the fires. RESULTS:
      There were 414 patients who presented to hospital EDs as a result of the
      bushfires. Patients were triaged at the emergency scene, at treatment centres and
      in hospital. National and statewide burns disaster plans were activated. Twenty
      two patients with burns presented to the state's burns referral centres, of whom
      18 were adults. Adult burns patients at The Alfred spent 48.7 hours in theatre in
      the first 72 hours. There were a further 390 bushfire-related ED presentations
      across the state in the first 72 hours. Most patients with serious burns were
      triaged to and managed at burns referral centres. Throughout the disaster, burns
      referral centres continued to have substantial surge capacity. CONCLUSIONS: Most
      bushfire victims either died, or survived with minor injuries. As a result of
      good prehospital triage and planning, the small number of patients with serious
      burns did not overload the acute health care system.

PMID- 19580530
TI  - National survey of management of transient ischaemic attack in Australia: take
      immediate action.
AB  - OBJECTIVE: To understand the current organisation of services for people with
      transient ischaemic attack (TIA) and the processes of assessment and management
      across Australian hospitals. DESIGN AND SETTING: Cross-sectional survey in 2008
      of 134 Australian hospitals, mostly urban centres that treat large numbers of
      stroke patients. MAIN OUTCOME MEASURES: Survey questions covered assessment,
      early management and follow-up practices, as well as organisation of services for
      TIA. RESULTS: Seventy-four hospitals (55%) responded: 47 (64%) reported access to
      a stroke unit, and 19 (26%) to a specialist clinic for TIA. Initial assessment
      included blood tests, electrocardiogram and brain computed tomography at most
      sites (92%-94%), and carotid imaging at more than half (65%), but magnetic
      resonance imaging at only 3% of sites. A tool to stratify the risk of subsequent
      stroke was used at 38 sites (51%), more commonly in hospitals with a stroke unit
      than in those without such a unit (64% v 30%; P = 0.005). Treatment was initiated
      at the initial assessment at 42 sites (58%), more commonly at stroke unit than
      non-stroke unit sites (68% v 37%; P = 0.007). Formalised policies for management
      of TIA patients were used at 38 sites (54%), with clear differences between sites
      with a stroke unit and those without (70% v 25%; P < 0.001). CONCLUSION: Access
      to rapid assessment and management services for TIA varies considerably between
      Australian hospitals. The presence of organised stroke care at a hospital leads
      to improved processes of care for patients presenting with TIA.

PMID- 19580531
TI  - Evaluation of non-invasive prenatal RHD genotyping of the fetus.
AB  - OBJECTIVE: To evaluate a non-invasive molecular test using free circulating fetal
      DNA in maternal plasma to predict the fetal RHD type. DESIGN: A prospective
      cohort study. PARTICIPANTS AND SETTING: Venous blood samples were collected from
      140 Rhesus (Rh) D-negative women booked for antenatal care in two tertiary
      maternity hospitals in Sydney and Brisbane between November 2006 and April 2008.
      Cell-free DNA, including free maternal and fetal DNA, was extracted from maternal
      plasma in the tertiary Australian Red Cross Blood Service laboratory, and three
      exon regions of the RHD gene were amplified. MAIN OUTCOME MEASURES: Comparison of
      the predicted fetal RHD status and the infant's RhD serotype. Secondary analysis
      involved using SRY and RASSF1A assays as internal controls to confirm the
      presence of fetal DNA in RHD-negative samples. RESULTS: Of 140 samples tested,
      results for RHD status were assigned for 135, and all 135 predictions were
      correct. A result was not assigned in five cases: three did not meet strict
      threshold criteria for classification, and two were due to RHD variants. Fetal
      SRY status was correctly predicted in 137 of 140 cases. In 16 samples typed both
      RHD- and SRY-negative, a positive RASSF1A result verified the presence of fetal
      DNA. CONCLUSIONS: Non-invasive testing of multiple exons provides a robust method
      of assessing fetal RHD status, and provides a safer alternative to amniocentesis
      for the management of RhD-negative pregnant women who are isoimmunised.

PMID- 19580532
TI  - The challenge for academic health partnerships.
AB  - The future of academic medicine in Australia has been identified as a significant
      issue, but received little mention in the interim report of the National Health
      and Hospitals Reform Commission. Australia is at particular risk of failing to
      capitalise on what is happening globally with academic medicine. New
      "partnerships" between health services, universities and health research
      institutes should be encouraged for stimulating research and learning across the
      health sector. Such partnerships can drive translational research, provide full
      costing of research, and establish national and international networks of
      researchers and research funding. There are many interactions between Australian
      state and federal jurisdictions and their hospitals and primary care
      organisations, but these are often loosely coordinated and with little
      understanding of how universities and research institutes can help to deliver
      better and more efficient health care. Academic health science centres, as
      recently designated by the National Health Service in the United Kingdom, provide
      a useful model for consideration in Australia.

PMID- 19580533
TI  - Making cars and making health care: a critical review.
AB  - The uncritical adoption of production-line manufacturing practices (such as "lean
      thinking") into work design processes in hospitals creates a fundamental tension
      between the production of health care and protection of the patient. There is
      scant evidence that re-engineering health care services in line with industrial
      models increases their efficiency. Indeed, reducing the richness of health care
      practice to impoverished snippets of work may add to the problems of hospital
      misadventure and inefficiency rather than solve them.

PMID- 19580534
TI  - Sustaining Medicare through consumer choice of health funds: lessons from the
      Netherlands.
AB  - The current escalation in costs of Australia's health care system does not appear
      to be sustainable. Sustainable financing requires direct engagement of consumers 
      instead of the current political process driven by special interest groups,
      targeted at gaining a larger share of the federal and state governments' budgets.
      Reforms in the Netherlands, directed at achieving universal insurance with
      consumer choice of health fund, provide valuable lessons for Australia on how to
      design sustainable financing.

PMID- 19580535
TI  - Building capacity in medical education research in Australia.
AB  - Medical education research is a relatively new but growing discipline. There is
      an overall perception of lack of confidence in the quality of the research, which
      is not entirely justified. The scientific quality of any research is defined by
      the appropriate application of method to a particular problem. There is a need
      for programmatic research focused on developing medical education policy.
      University medical education units need to be research-focused. Medical Deans
      Australia and New Zealand and the Australian and New Zealand Association of
      Medical Education (ANZAME: the Association for Health Professional Education) can
      provide leadership. Funding bodies need to develop their relationship with
      medical education research.

PMID- 19580536
TI  - Medical education: revolution, devolution and evolution in curriculum philosophy
      and design.
AB  - Contemporary medical education must train skilled and compassionate health care
      professionals who are rigorous in their approach to patient care and their
      pursuit of knowledge and solutions. Problem-based learning has been widely
      introduced, but there is no evidence that it leads to better outcomes than more
      traditional programs, and fundamental gaps in conceptual knowledge may result.
      Recently, emphasis has been placed on a solid grounding in underlying concepts
      combined with a systems-based approach, and ability to transfer information and
      solve problems. Integrating traditional scientific and clinical disciplines with
      progressive and continuous assessment, may be a better means of achieving the
      combined aims of clinically relevant curriculum design, vertical integration of
      medical knowledge, and facilitation of the continuum of training. Being adaptable
      and flexible, cognisant of costs, and driven by evidence are key features of
      delivering medical education and contemporary medical practice. Educational
      research should lead to continuous improvement, but innovation without evaluation
      and attention to costs may create as many, or more, problems as are solved.

PMID- 19580537
TI  - A pandemic that's not bird flu? Pigs might fly.
AB  - With the recent outbreak of swine influenza, the world may be facing this
      century's first influenza pandemic. In Mexico, around 2000 patients have been
      hospitalised with respiratory illness and almost 150 people have died. Several
      other countries have reported smaller numbers of suspected and confirmed cases of
      swine influenza. This 2009 influenza A virus is a strain of the H1N1 subtype, and
      appears to be a human-avian reassortment swine virus influenza. It is likely that
      sustained human-to-human transmission of swine influenza has occurred, at least
      in Mexico. Despite there being so many hospitalised patients in Mexico, cases
      outside Mexico have demonstrated a mild influenza-like illness, with only one
      fatality to date. In contrast to the 1918 influenza pandemic, we now have a more
      robust public health system, with widespread global networks; vaccines can be
      developed rapidly; and there are antiviral medications to which the swine
      influenza A(H1N1) virus is sensitive. Many resources have been invested in
      pandemic preparedness programs in the health care and public health systems in
      Australia over the past few years.

PMID- 19580538
TI  - Hand-foot syndrome after treatment with docetaxel.

PMID- 19580539
TI  - Congenital tuberculosis after in-vitro fertilisation.
AB  - A 6-week old infant who had been conceived through in-vitro fertilisation (IVF)
      presented with a skin lesion and enlarged lymph nodes, and developed severe
      respiratory distress. Mycobacterium tuberculosis was identified; his mother was
      the only potential source identified. To our knowledge, this is the first case of
      congenital tuberculosis after IVF reported in Australia and the second worldwide.
      It highlights the importance of adequate screening during investigation of
      infertility and the difficulties in diagnosing congenital tuberculosis.

PMID- 19580540
TI  - Paradoxical nutritional deficiency in overweight and obesity: the importance of
      nutrient density.

PMID- 19580541
TI  - Acute lingual tonsillitis: an overlooked cause of severe sore throat in adults
      who have had a palatine tonsillectomy?

PMID- 19580542
TI  - Childhood obesity in Australia remains a widespread health concern that warrants
      population-wide prevention programs.

PMID- 19580543
TI  - Comparison of the Framingham and United Kingdom Prospective Diabetes Study
      cardiovascular risk equations in Australian patients with type 2 diabetes from
      the Fremantle Diabetes Study.

PMID- 19580545
TI  - Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered
      protein.
AB  - Pup (prokaryotic ubiquitin-like protein) from Mycobacterium tuberculosis is the
      first ubiquitin-like protein identified in non-eukaryotic cells. Although
      different ubiquitin-like proteins from eukaryotes share low sequence similarity,
      their 3D (three-dimensional) structures exhibit highly conserved typical
      ubiquitin-like folds. Interestingly, our studies reveal that Pup not only shares
      low sequence similarity, but also presents a totally distinguished structure
      compared with other ubiquitin-like superfamily proteins. Diverse structure
      predictions combined with CD and NMR spectroscopic studies all demonstrate that
      Pup is an intrinsically disordered protein. Moreover, 1H-15N NOE (nuclear
      Overhauser effect) data and CSI (chemical shift index) analyses indicate that
      there is a residual secondary structure at the C-terminus of Pup. In M.
      tuberculosis, Mpa (mycobacterium proteasomal ATPase) is the regulatory cap ATPase
      of the proteasome that interacts with Pup and brings the substrates to the
      proteasome for degradation. In the present paper, SPR (surface plasmon resonance)
      and NMR perturbation studies imply that the C-terminus of Pup, ranging from
      residues 30 to 59, binds to Mpa probably through a hydrophobic interface. In
      addition, phylogenetic analysis clearly shows that the Pup family belongs to a
      unique and divergent evolutionary branch, suggesting that it is the most ancient
      and deeply branched family among ubiquitin-like proteins. This might explain the
      structural distinction between Pup and other ubiquitin-like superfamily proteins.

PMID- 19580544
TI  - Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and
      interacts with the ubiquitin E3 ligases AIP4 and AIP5.
AB  - The HSPs (hereditary spastic paraplegias) are genetic conditions in which there
      is distal degeneration of the longest axons of the corticospinal tract, resulting
      in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer
      syndrome, an HSP in which paralysis is accompanied by additional clinical
      features. There has been controversy over the subcellular distribution of
      spartin. We show here that, at steady state, endogenous spartin exists in a
      cytosolic pool that can be recruited to endosomes and to lipid droplets.
      Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it
      interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin
      interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue]
      [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not
      required for spartin's ubiquitination, and so we propose that spartin acts as an
      adaptor for these proteins. Our results suggest that spartin is involved in
      diverse cellular functions, which may be of relevance to the complex phenotype
      seen in Troyer syndrome.

PMID- 19580546
TI  - Foreword: Values, empathy, and fairness across social barriers.

PMID- 19580547
TI  - Lethal altruists: itineraries along the dark outskirts of moralistic
      prosociality.
AB  - Suicide bombers are the most spectacular example of an impregnable morality
      toward one's own group that co-exists alongside a radical amorality toward
      members of another group. Suicide bombers carry out massacres with the utter
      conviction that they are acting in accordance with values associated with the
      greatest good. Suicidal attacks are conceived as a form of lethal altruism, a
      damaging drift from human cooperative tendencies and one that requires a detailed
      understanding. Strong altruism is a main component of a cluster of temperamental
      traits that may distinguish individuals with propensities to put themselves at
      the threshold of major progroupal sacrifices. Among all populations there will be
      pockets of extreme moralizing altruists willing to make high investments in
      others, investments involving great personal risk. A research framework is
      outlined to study other constitutionally based traits (dominance, boldness,
      aggressiveness, machiavellianism, narcissism, messianism, credulity/religiosity)
      that may also contribute to the different roles played by self-recruited members
      in combative cells that in turn are crucial for the ties they establish and the
      tactics employed. Individually oriented research may reveal profiles
      distinguishing between potential inducers and performers of martyrdom. As a rule,
      machiavellistic leaders do not usually squander their personal choices on group
      commitments; on the contrary, their gift for simulating altruism is used for
      individual gains. Potential martyrs, on the other hand, are by definition
      squanderers. Evidence accrued in recent years in fields going from behavioral
      economics to cognitive neuroimaging makes such an endeavor feasible.

PMID- 19580549
TI  - From dehumanization and objectification to rehumanization: neuroimaging studies
      on the building blocks of empathy.
AB  - Social neuroscience offers a window into the mental origins of empathy. People
      must appreciate another mind in order to empathize. People first categorize the
      other as human, assuming a mind, and then differentiate among social categories
      according to universal dimensions of perceived traits: warmth and competence. The
      least warm and competent groups (poor people, homeless, drug addicts) may even be
      denied humanity and a meaningful mind, according to both neural and behavioral
      responses to allegedly disgusting outcasts. Other groups may be instead envied
      and viewed as tools or automatons, that is, objectified. The patterns can reverse
      when perceivers must consider the other's preferences, that is, appreciate the
      other's mind.

PMID- 19580548
TI  - The need for a cognitive neuroscience of naturalistic social cognition.
AB  - Understanding the minds of others is one of the great challenges humans face.
      Accordingly, much work in cognitive neuroscience has explored the brain systems
      engaged when perceivers share and make inferences about the internal states of
      social targets. These studies, however, typically use divergent and highly
      simplified stimuli and methods and as a consequence have produced largely non
      overlapping sets of results and artificially constrained theories about the
      processes involved in perceivers' abilities to understand targets. Here we
      suggest that these difficulties may stem from two main sources: the lack of
      meaningful behavioral data about the brain bases of perceivers' accuracy in
      inferring target states and qualitative differences between the social stimuli
      used in neuroimaging paradigms and the social information perceivers encounter in
      the real world. We advocate more focus on studies of naturalistic social
      cognition, which could overcome these limitations and complement current
      approaches, and discuss work in our laboratory that has demonstrated the
      feasibility and utility of such a focus. Finally, we discuss the relevance of
      naturalistic social cognition to diagnosing and treating autism spectrum
      disorder. Overall, using naturalistic paradigms in neuroimaging will be critical
      to modeling the way the brain actually understands other minds.

PMID- 19580550
TI  - When the self becomes other: toward an integrative understanding of the processes
      distinguishing adaptive self-reflection from rumination.
AB  - How can people adaptively analyze and "work through" negative feelings without
      ruminating? This paper will briefly review findings from an integrative program
      of research, which suggests that a critical factor determining whether people's
      attempts to adaptively reason about negative experiences succeed or fail is the
      type of self-perspective they adopt. That is, whether people analyze their
      feelings from a self-immersed or self-distanced perspective. The implications of
      shifting self-perspectives for subjective experience, autonomic nervous system
      reactivity, and neural activity are discussed.

PMID- 19580551
TI  - Differential roles of fairness- and compassion-based motivations for cooperation,
      defection, and punishment.
AB  - The present paper briefly describes and contrasts two different motivations
      crucially involved in decision making and cooperation, namely fairness-based and
      compassion-based motivation. Whereas both can lead to cooperation in comparable
      social situations, we suggest that they are driven by fundamentally different
      mechanisms and, overall, predict different behavioral outcomes. First, we provide
      a brief definition of each and discuss the relevant behavioral and
      neuroscientific literature with regards to cooperation in the context of economic
      games. We suggest that, whereas both fairness- and compassion-based motivation
      can support cooperation, fairness-based motivation leads to punishment in cases
      of norm violation, while compassion-based motivation can, in cases of defection,
      counteract a desire for revenge and buffer the decline into iterative
      noncooperation. However, those with compassion-based motivation alone may get
      exploited. Finally, we argue that the affective states underlying fairness-based
      and compassion-based motivation are fundamentally different, the former driven by
      anger or fear of being punished and the latter by a wish for the other person's
      well-being.

PMID- 19580553
TI  - Genoeconomics: promises and caveats for a new field.
AB  - Since the publication 150 years ago of the Origin of Species, the scientific
      study of the evolution of human-specific traits has been the focus of many
      efforts from very different areas of science. Nowadays, after a century and a
      half of research, impressive results have accumulated, particularly about those
      traits that presumably would "make us human," setting us apart from the rest of
      primates, and about how these traits would have evolved. Over the last few years,
      a new area of research, genoeconomics, has started to make important
      contributions toward the study of hominization. Here, I review the foundations
      and promises of this new branch of science and discuss a few of the pitfalls that
      may hinder its advance.

PMID- 19580552
TI  - The development of adolescent social cognition.
AB  - Adolescence has long been considered a turbulent time; beginning with large
      changes in hormonal levels and consequent bodily changes, as well as changes in
      behavior. Recently, neuroscience studies have contributed to this picture of
      turbulence. We now know that the brain undergoes profound transformation during
      the teenage years. This paper focuses on how the social brain--the network of
      brain regions involved in understanding other people and self-awareness--develops
      during adolescence.

PMID- 19580554
TI  - Experimental game theory and behavior genetics.
AB  - We summarize the findings from a research program studying the heritability of
      behavior in a number of widely used economic games, including trust, dictator,
      and ultimatum games. Results from the standard behavior genetic variance
      decomposition suggest that strategies and fundamental economic preference
      parameters are moderately heritable, with estimates ranging from 18 to 42%. In
      addition, we also report new evidence on so-called "hyperfair" preferences in the
      ultimatum game. We discuss the implications of our findings with special
      reference to current efforts that seek to understand the molecular genetic
      architecture of complex social behaviors.

PMID- 19580555
TI  - The neurochemistry of fairness: clarifying the link between serotonin and
      prosocial behavior.
AB  - Decades of research have linked the neurotransmitter serotonin (5-HT) to
      prosocial behavior. However, the precise mechanisms through which 5-HT influences
      social interactions remain unclear. A neuroeconomics approach may help clarify
      these mechanisms. In a recent study, lowering 5-HT levels in healthy volunteers
      enhanced their reactions to unfair treatment in the ultimatum game. Other studies
      investigating the neural mechanisms of social decision making have implicated
      brain regions that are modulated by 5-HT. Here, I review the evidence for the
      role of 5-HT in modulating social decision making and discuss the implications
      for understanding how prosocial behavior varies between individuals and across
      social contexts.

PMID- 19580556
TI  - Arginine vasopressin and oxytocin modulate human social behavior.
AB  - Increasing evidence suggests that two nonapeptides, arginine vasopressin and
      oxytocin, shape human social behavior in both nonclinical and clinical subjects.
      Evidence is discussed that in autism spectrum disorders genetic polymorphisms in
      the vasopressin-oxytocin pathway, notably the arginine vasopressin receptor 1a
      (AVPR1a), the oxytocin receptor (OXTR), neurophysin I and II, and CD38 (recently
      shown to be critical for social behavior by mediating oxytocin secretion)
      contribute to deficits in socialization skills in this group of patients. We also
      present first evidence that CD38 expression in lymphoblastoid cells derived from
      subjects diagnosed with autism is correlated with social skill phenotype
      inventoried by the Vineland Adaptive Behavioral Scales. Additionally, we discuss
      molecular genetic evidence that in nonclinical subjects both AVPR1a and OXTR
      genes contribute to prosocial or altruistic behavior inventoried by two
      experimental paradigms, the dictator game and social values orientation. The role
      of the AVPR1a is also analyzed in prepulse inhibition. Prepulse inhibition of the
      startle response to auditory stimuli is a largely autonomic response that
      resonates with social cognition in both animal models and humans. First results
      are presented showing that intranasal administration of arginine vasopressin
      increases salivary cortisol levels in the Trier Social Stress test. To summarize,
      accumulating studies employing a broad array of cutting-edge tools in psychology,
      neuroeconomics, molecular genetics, pharmacology, electrophysiology, and brain
      imaging are beginning to elaborate the intriguing role of oxytocin and arginine
      vasopressin in human social behavior. We expect that future studies will continue
      this advance and deepen our understanding of these complex events.

PMID- 19580557
TI  - Empathy in early childhood: genetic, environmental, and affective contributions.
AB  - We investigated the genetic and environmental origins of children's empathy
      toward a distress victim and its correlates with emotional symptoms and affective
      knowledge. The cognitive (hypothesis testing) and affective (empathic concern)
      empathy of 122 twin pairs in response to simulated pain by an adult examiner was
      observed at 3.5 years of age. Moderate (0.19 to 0.44) heritabilities were
      estimated for individual differences in empathy, and the nonshared environment
      and error accounted for the rest of the variance. Hypothesis testing and empathic
      concern were moderately correlated, mainly through overlapping genetic effects.
      Although children's affective knowledge did not correlate with their empathy,
      affective knowledge interacted with mother-rated emotional symptoms in predicting
      empathy; knowledge about emotions was associated with greater empathy in children
      low in emotional symptoms. In contrast, among children with high degrees of
      emotional symptoms, those with better affective knowledge tended to show lower
      empathy.

PMID- 19580558
TI  - What motivates participation in violent political action: selective incentives or
      parochial altruism?
AB  - In standard models of decision making, participation in violent political action
      is understood as the product of instrumentally rational reasoning. According to
      this line of thinking, instrumentally rational individuals will participate in
      violent political action only if there are selective incentives that are limited
      to participants. We argue in favor of an alternate model of political violence
      where participants are motivated by moral commitments to collective sacred
      values. Correlative and experimental empirical evidence in the context of the
      Israeli-Palestinian conflict strongly supports this alternate view.

PMID- 19580559
TI  - Sex differences in intergroup competition, aggression, and warfare: the male
      warrior hypothesis.
AB  - The social science literature abounds with examples of human tribalism, the
      tendency to categorize individuals on the basis of their group membership and
      treat in-group members benevolently and out-group members malevolently. I argue
      that this tribal inclination is an evolved response to the threat of intergroup
      violence and warfare that was endemic in ancestral human environments (and is
      still common today). Here I hypothesize that intergroup conflict has profoundly
      affected the social psychology of human males in particular--the male warrior
      hypothesis--and present evidence consistent with this claim. I also discuss
      implications of this hypothesis for managing intergroup relations in our society.

PMID- 19580560
TI  - Precis of implicit nationalism.
AB  - While the study of nationalism has received much attention throughout the social
      sciences and humanities, the experimental investigation of it lags behind. In
      this paper we review recent advances in the examination of implicit nationalism.
      In the first set of experiments we survey, the Palestinian, Israeli, Italian, and
      Russian flags were primed (or not, in the control conditions) and their effects
      on political thought and behavior were tested. In the second set the American or
      the Israeli flag was primed (or not) and prejudice toward African-Americans or
      Palestinians (respectively) was examined. The results of all experiments suggest
      that the implicit activation of national cues has far-reaching implications on
      political thought and behavior as well as on attitudes toward minorities. Under
      the assumption that the image of national flags is associated in memory with
      national ideologies, these results suggest that national ideologies can be
      implicitly pursued in a way that significantly affects our thoughts and
      behaviors.

PMID- 19580561
TI  - Reason within passion: values as motivational anchors of Israeli opinion on the
      2006 Lebanon war and ceasefire.
AB  - The relationship between core values and political opinions has been well
      documented but its implications for citizens' awareness of the reasons that
      ground competing opinions are less well understood. This study examines the
      effect of value priorities on rating different rationales for a government
      decision to end a war. The relationship is tested among Israelis in the days
      following the aftermath of the 2006 Israel-Hezbollah war in Lebanon. Consistent
      with previous research, values, such as universalism, predicted dovish or hawkish
      positions on the ceasefire. In addition, however, different value priorities
      correlated, as expected, with their respective rationales for an opinion on the
      ceasefire. Moreover, both supporters and opponents evaluated valid (versus
      invalid) reasons as more important, regardless of their personal position.
      Overall findings suggest that, even in conflict, reasoned considerations resonate
      with the opinions of ordinary citizens.

PMID- 19580562
TI  - Sacred values: psychological and anthropological perspectives on fairness,
      fundamentalism, and terrorism.
AB  - Enduring, violent, social, and political conflicts have often been interpreted as
      resulting directly from socioeconomic inequity. The advent of global terrorism is
      traditionally understood by the political left as representing a rational, albeit
      regrettable, third-world response to poverty. On the political right the
      alternative explanation tends to see the world in terms of the fight between good
      and evil--each side "Islamist" and "Western," characterizing the enemy in similar
      opposing terms. This has recently been popularized as a clash of religions,
      cultures, or civilizations. Most poor societies do not, however, respond to their
      circumstances with violence (particularly terrorism), and indeed it is often at
      the point where the socioeconomic circumstances of a society or a region are
      improving that there is a breakdown into violence. Starting in Northern Ireland
      and then exploring other regions, including Peru, Nepal, and the Middle East, the
      author's close observation of a number of societies where there has been
      persistent terrorism has revealed that the response is an emotional and self
      destructive one rather than being marked by rational economic self-interest or an
      essentially religious/cultural conflict; it is often the sense of humiliation,
      disrespect, and injustice that is the most toxic stimulus; and, insofar as there
      is inequity or cultural division, it is the component of "unfairness" or
      "injustice" that is the potent element in the predisposing mixture. "Righting a
      terrible wrong" or responding to unfairness and injustice is, therefore, a key to
      understanding and addressing such violent social conflicts.

PMID- 19580563
TI  - Neural basis of preference for human social hierarchy versus egalitarianism.
AB  - A fundamental way that individuals differ is in the degree to which they prefer
      social dominance hierarchy over egalitarianism as a guiding principle of societal
      structure, a phenomenon known as social dominance orientation. Here we show that
      preference for hierarchical rather than egalitarian social relations varies as a
      function of neural responses within left anterior insula and anterior cingulate
      cortices. Our findings provide novel evidence that preference for social
      dominance hierarchy is associated with neural functioning within brain regions
      that are associated with the ability to share and feel concern for the pain of
      others; this suggests a neurobiological basis for social and political attitudes.
      Implications of these findings for research on the social neuroscience of
      fairness, justice, and intergroup relations are discussed.

PMID- 19580564
TI  - Empathy toward strangers triggers oxytocin release and subsequent generosity.
AB  - Empathy is related to a variety of prosocial behaviors, but the brain mechanisms
      producing the experience of empathy have not been fully characterized. This study
      investigated whether the experience of empathy raises oxytocin levels and affects
      subsequent generosity toward strangers. Short video clips of an emotional scene
      and an unemotional scene were used as stimuli. Participants rated the emotions
      they experienced and then played a $40 ultimatum game to gauge their generosity.
      We found that empathy was associated with a 47% increase in oxytocin from
      baseline. We also found the empathy-oxytocin response was stronger in women than
      in men. Higher levels of empathy were also associated with more generous monetary
      offers toward strangers in the ultimatum game. Our findings provide the first
      evidence that oxytocin is a physiologic signature for empathy and that empathy
      mediates generosity.

PMID- 19580565
TI  - On hotheads and Dirty Harries: the primacy of anger in altruistic punishment.
AB  - Recent research has shown that individuals are prepared to incur costs to punish
      non-cooperators, even in one-shot interactions. However, why would people punish
      non-cooperators with no apparent benefits for the punishers themselves? This
      behavior is also known as altruistic punishment. When defection is discovered, an
      individual evaluates this act as unfair, which could result in anger. We argue
      that although unfairness and anger are often intertwined, it is primarily the
      experience of anger and not the perception of unfairness that produces altruistic
      punishment. We briefly present recent data in line with the hypothesis that
      identifies anger as the underlying mechanism of altruistic punishment.
      Furthermore, additional influences regarding the occurrence of altruistic
      punishment, e.g., intentionality of the interaction partner, the role of
      satisfaction, and individual differences, are discussed.

PMID- 19580566
TI  - Neural correlates of social decision making and relationships: a developmental
      perspective.
AB  - Social competence, e.g., effective functioning in interpersonal relationships,
      plays an important role in well being during one's lifetime. Social skills, such
      as perspective taking and understanding intentionality, develop during childhood
      and adolescence. We hypothesize that these behavioral changes result from
      protracted development of brain regions involved in social interactions. We give
      a brief outline of behavioral and neuroimaging studies on fairness, trust, and
      reciprocity considerations in social decision making and the development of these
      considerations. We propose that a better understanding of the mechanisms
      underlying the developing brain and sociocognitive skills is important for
      understanding the development of social relationships.

PMID- 19580567
TI  - Suicidality connected with mentalizing anomalies in schizophrenia: a study with
      stabilized outpatients.
AB  - Deficits in social cognition contribute to the severe difficulties in daily
      functioning of schizophrenic patients, although they have never been connected
      with suicidality. Theory of mind (ToM) tasks explore basic social abilities and
      have been found to be defective in schizophrenia. The relationship between ToM
      anomalies and suicidal history was studied in a sample of 57 stabilized
      outpatients. Logistic regression analysis showed an association between poor
      performance on second-order ToM tasks and a greater likelihood of suicidality in
      schizophrenic patients (OR = 4.02, 95% CI 1.18-13.62), which was independent of
      current clinical and neuropsychological status, with the exception of poor
      premorbid adjustment in infancy and adolescence. We caution against potential
      biases from mixing cross-sectional ToM scores with lifetime suicidal records and
      retrospective assessments of premorbid adjustment through repeated testing of
      patients and their relatives. Hence, the present findings suggest that ToM
      deficits may contribute to the high risk of suicide in schizophrenia.

PMID- 19580568
TI  - Neurobiological substrates of social cognition impairment in attention-deficit
      hyperactivity disorder: gathering insights from seven structural and functional
      magnetic resonance imaging studies.
AB  - Social cognitive neuroscience is beginning to unravel a neuroanatomy of social
      cognition, networks of brain regions especially involved in social cognition and
      social functioning. It is widely acknowledged that social functioning and social
      cognition are impaired in attention-deficit hyperactivity disorder (ADHD).
      Although an impressive amount of neuroscientific research has been conducted in
      ADHD, little effort has been made to link those deficits in social cognition and
      functioning to the well-known brain abnormalities detected in structural and
      functional neuroimaging studies. We review seven functional and magnetic
      resonance studies conducted at our laboratory in ADHD samples during the last 5
      years in order to scrutinize whether the putative neuroanatomic regions
      underpinning social cognition are affected in ADHD. The orbitofrontal cortex
      (OFC), the caudate nucleus, the ventral striatum, and the cerebellum are among
      those regions that displayed functional or morphometric abnormalities in our ADHD
      samples. The OFC is clearly involved in social cognition, and several features of
      OFC dysfunction may be related to the social cognition and function impairment in
      ADHD. In contrast to the OFC, the role of the caudate nucleus, the ventral
      striatum, and the cerebellum is elusive. However, on one hand, there is
      converging evidence from human and animal neuropsychology, neuroscience, and
      psychiatry that support the role of such areas in social cognition, mainly
      through its involvement in emotional processing. On the other hand, the
      morphometric and functional ADHD abnormalities in these regions could account for
      the impoverished social functioning and the deficient social cognition skills of
      ADHD children.

PMID- 19580569
TI  - Agent-based computer simulations of language choice dynamics.
AB  - We use agent-based Monte Carlo simulations to address the problem of language
      choice dynamics in a tripartite community that is linguistically homogeneous but
      politically divided. We observe the process of nonlocal pattern formation that
      causes populations to self-organize into stable antagonistic groups as a result
      of the local dynamics of attraction and influence between individual
      computational agents. Our findings uncover some of the unique properties of
      opinion formation in social groups when the process is affected by asymmetric
      noise distribution, unstable intergroup boundaries, and different migratory
      behaviors. Although we focus on one particular study, the proposed stochastic
      dynamic models can be easily generalized and applied to investigate the evolution
      of other complex and nonlinear features of human collective behavior.

PMID- 19580570
TI  - The use of supernatural entities in moral conversations as a cultural
      psychological attractor.
AB  - Social behavior in most human societies is characterized by the following of
      moral rules explicitly justified by religious belief systems. These systems
      constitute the diverse domain of human sacred values. Supernatural entities as
      founders or warranty of moral principles may be seen as a form of "conversation
      stoppers," considerations that can be dropped into a moral decision process in
      order to prevent endlessly reconsidering and endlessly asking for further
      justification. In this article we offer a general naturalistic framework toward
      answering the question of why supernatural entities are so attractive in moral
      argumentation. We present an explanatory model based on the phenomena of multiple
      channels of moral reasoning, the suspension of epistemic vigilance, and relevance
      assumptions through the attractiveness of the sacred, moral dumbfounding, and the
      expression of social coalitionary commitment. Thus, in light of much of current
      cognitive theory, sacred values make sense as basins in the evolutionary
      landscape of human morality.

PMID- 19580571
TI  - Retraction.

PMID- 19580573
TI  - Treatment of infestations, vector-borne, and zoonotic diseases.

PMID- 19580574
TI  - Treatment of head lice.
AB  - Pediculosis capitis, or head lice, is a common infestation among children
      worldwide. Multiple therapies exist for the treatment of this condition,
      including topical pediculicides and oral medications. When used in combination
      with environmental decontamination, these drugs can be very effective in
      eradicating head lice infestation without significant adverse events. The present
      study discusses the use of available over-the-counter and prescription
      treatments, including pyrethroids and permethrin, lindane, malathion, ivermectin,
      and trimethoprim-sulfamethoxazole, in the treatment of head lice.

PMID- 19580575
TI  - Scabies.
AB  - Scabies is an ectoparasite caused by the mite Sarcoptes scabiei var hominis, an
      obligate human parasite. There are about 300 million cases of scabies in the
      world each year. Common predisposing factors are overcrowding, immigration, poor
      hygiene, poor nutritional status, homelessness, dementia, and sexual contact.
      Direct skin-to-skin contact between 15 and 20 minutes is needed to transfer the
      mites from one person to another. The diagnosis suspected with a clinical history
      of itch, worse at night, affecting other family members, clinical distribution,
      and appearance. Definite diagnosis relies on microscopic identification of the
      mites, eggs, or fecal pellets with 10% potassium hydroxide, ink enhancement,
      tetracycline fluorescence tests, or mineral oil; other methods include:
      epiluminescence light microscopy and S. scabiei DNA. The most commonly used
      treatment modalities are permethrin and ivermectin. Persistence of symptoms for 2
      6 weeks after successful treatment is common. Most recurrences are because of
      reinfection from untreated contacts.

PMID- 19580576
TI  - Diagnosis and treatment of tick infestation and tick-borne diseases with
      cutaneous manifestations.
AB  - Hard and soft ticks may be associated directly or indirectly with a number of
      dermatoses, both infectious and inflammatory in origin. Morbidity may occur as a
      result of tick bites, tick toxicosis, and even infestation. These arthropod
      vectors may transmit life-threatening protozoan, bacterial, rickettsial, and
      viral diseases with systemic and cutaneous findings. Additionally, ticks may
      transmit more than one pathogen with subsequent human coinfection. This article
      reviews the presentation of tick-borne illnesses and the medical management of
      these diseases. Among others, diseases such as ehrlichiosis, anaplasmosis,
      babesiosis, tularemia, borrelioses, tick-borne encephalitides, rickettsial
      spotted fevers, and tick typhus are discussed in this article. The recognition of
      skin manifestations associated with these diseases is paramount to early
      diagnosis and treatment initiation.

PMID- 19580577
TI  - Mite infestations.
AB  - Mite infestations are important in dermatology because these may cause
      dermatologic diseases that range from papulosquamous eruptions to urticarial
      lesions to bullous eruptions and may spread infectious diseases. These clinical
      manifestations are important to recognize because mite-associated diseases may
      have systemic complications and may be confused with other dermatologic
      conditions. In treating mite infestations, oral antibiotics may be necessary.
      Prevention of infestation may be accomplished by pre-treating clothing with
      permethrin, using insect repellent N,N-Diethyl-meta-toluamide on clothing and
      skin, and treating animals infected with mites. This article will review
      etiology, clinical manifestation, and treatment of mite infestations.

PMID- 19580578
TI  - Bedbugs.
AB  - Cimex lectularius (the "bedbug") is an insect that feeds nocturnally, taking a
      requisite blood meal from a sleeping human or other parasitized host.
      Immunological reactions to bedbug saliva vary, but typically, bites yield
      erythematous and pruritic papules. The face and distal extremities, areas
      uncovered by sleeping clothes or blankets, are preferentially involved. Until the
      late 1990s, bedbug infestations in the United States were declining. Resurgence
      is attributed to increased travel and resistance to insecticides. Although
      hepatitis or human immunodeficiency virus is not effectively transmitted by the
      bedbug, pruritus and the fear and perceived violation of an infestation can be
      debilitating. Bedbugs are small but robust, and their ability to remain ensconced
      in crevices within the bedroom makes eradication difficult. As more patients
      present with bedbug bites, physicians must possess the knowledge to diagnose,
      treat, and educate with regard to bedbug bites and bedbug infestations.

PMID- 19580579
TI  - Caterpillars and moths.
AB  - Lepidoptera (moths, butterflies, and caterpillars) are an uncommon cause of
      adverse reactions in humans. Most reactions to Lepidoptera are mild and self
      limited; however, reactions in sensitive individuals and reactions to particular
      species can be severe and life threatening. Specific syndromes caused by
      Lepidoptera include erucism (cutaneous reactions from contact with caterpillars,
      moths, or cocoons), lepidopterism (systemic involvement), ophthalmia nodosa
      (ocular involvement), dendrolimiasis and pararamose (each with joint symptoms
      relating to a specific species of caterpillar), lonomism (a severe hemorrhagic
      disease related to Lonomia species), and seasonal ataxia (related to ingestion of
      Anaphe venata). In most cases, reactions to Lepidoptera can be treated
      symptomatically with prompt removal of offending hairs. Antipruritic or
      anesthetic topical preparations, topical steroids, and oral antihistamines are
      often used. In the case of potentially fatal Lonomia envenomation, an effective
      antivenin has been manufactured.

PMID- 19580580
TI  - Zoonoses of dermatologic interest.
AB  - Zoonoses are infectious diseases that can be transmitted from animals to humans.
      Transmission occurs directly or through vectors such as ticks, mosquitoes, or
      flies. The causative agents include bacteria, parasites, viruses, and fungi.
      Domestic pets and livestock, as well as wild animals, can be the source of
      disease. In this summary, we will focus on a number of dermatologically relevant
      examples.

PMID- 19580581
TI  - Angiomatous reaction Kaposi-sarcoma-like as a side effect of topical
      corticosteroid therapy in lichen sclerosus of the penis.
AB  - Lichen sclerosus (LS) is a chronic inflammatory skin condition usually located in
      the anogenital area. Topical corticosteroid therapy is the first choice treatment
      which may arrest or delay the progression of the disorder. We report the case of
      a 74-year-old man presented with a 6-month history of nodular lesions localized
      on penis. The man had a previous history of genital lesions that had been
      diagnosed as LS and treated with long-term topical corticosteroid therapy. After
      3 months of corticosteroid therapy, the patient observed the appearance of
      several nodular erythematous lesions on the penis with progressive disappearance
      of the clinical symptoms of LS. These purple to red asymptomatic angiomatoid
      nodules resembled the clinical features of Kaposi sarcoma.

PMID- 19580582
TI  - Focused UV-B narrowband microphototherapy (Biopsorin). A new treatment for plaque
      psoriasis.
AB  - Skin irradiation with ultraviolet light B (UV-B) and in particular the emission
      peak at 311 nm represents an effective therapeutic regimen for psoriasis.
      Excessive tanning, photoaging, and skin cancerization do occur mainly in subjects
      with skin phototype I to III. The possibility of developing skin cancer is
      parallel to the skin surface area under treatment and to the overall irradiation
      dose. We report here on a new focused phototherapy method releasing UV-B with a
      peak at 311 nm, which consists in the selective irradiation of single psoriatic
      patches with a new device equipped with a special optic fiber. The treatment is
      effective, safe and well tolerated. Psoriasis Area and Severity Index 75 is
      achieved in 64% of patients after 12 sessions of treatment. The Physician Global
      Assessment evaluation significantly improves in all treated patients.

PMID- 19580583
TI  - Switch from etanercept to efalizumab in a psoriatic patient with HCV infection: a
      case report.
AB  - Psoriasis vulgaris is a chronic dermatosis and is a widespread dematological
      disease. The most represented lesions are erythemato-squamous plaques with a
      tendency to cover large body areas with a great impairment of normal activities
      and a poor quality of life. Very often psoriasis is associated to other illnesses
      and the dermatologist has to be aware that comorbidities have to be taken in
      account for a successfull treatment of the disease. We report a case of a patient
      affected by severe psoriasis and HCV infection. He underwent a first treatment
      with etenarcept with good clinical results and no change of his viral load. When
      etenarcept became ineffective, he received efalizumab, with a good control of his
      dermatological condition and a reduction of the viral load.

PMID- 19580584
TI  - Monochromatic excimer light 308 nm in monotherapy and combined with topical
      khellin 4% in the treatment of vitiligo: a controlled study.
AB  - Vitiligo is an acquired depigmentation disorder affecting 1-4% of the world's
      population. Conventional therapies include steroids, photosensitive topical
      agents, surgical treatments, and phototherapy. The aim of the study was to
      evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a
      monotherapy and in combination with khellin 4% ointment in vitiligo. Forty-height
      patients (36 male and 12 female) affected with vitiligo were enrolled in this
      open prospective study. Patients were selected and divided into three groups:
      group I included 16 patients treated with MEL 308 nm once-weekly and oral vitamin
      E; group II included 16 patients treated with MEL 308 nm once-weekly combined
      with khellin 4% ointment (MEL-K) and oral vitamin E; group III (control group)
      included 16 patients treated only with oral vitamin E. Efficacy was assessed at
      the end of 12 weeks based on the percentage of repigmentation. Group I (MEL
      group) showed a moderate repigmentation in 2/16 (12.5%) patients, good
      repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%)
      patients. Group II (MEL-K group) presented moderate repigmentation in 2/16
      (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent
      repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate
      repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%)
      patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The
      clinical response achieved in group I and II was higher compared with group III
      (control group) without showing significant differences. MEL 308 nm, alone and/or
      combined with khellin 4% offered encouraging results and it may be considered a
      valid therapeutic option worthy of consideration in the treatment of vitiligo.

PMID- 19580586
TI  - Integrating physiological, ecological and evolutionary change: a Price equation
      approach.
AB  - We use a general quantitative framework--the Price equation--to partition
      phenotypic responses to environmental change into separate physiological,
      evolutionary and ecological components. We demonstrate how these responses, which
      potentially occur over different timescales and are usually studied in isolation,
      can be combined in an additive way; and we discuss the main advantages of doing
      this. We illustrate our approach using two worked examples, concerning the
      emergence of toxin resistance within microbial communities, and the estimation of
      carbon uptake by marine phytoplankton in high-CO2 environments. We find that this
      approach allows us to exclude particular mechanistic hypotheses with regard to
      community-level transformations, and to identify specific instances where
      appropriate data are lacking. Thus Price's equation provides not only a powerful
      conceptual aid, but also a means for testing hypotheses and for directing
      empirical research programmes.

PMID- 19580587
TI  - Short and long term consequences of increases in exotic species richness on water
      filtration by marine invertebrates.
AB  - Although recent research has considered the consequences of global declines in
      the number of species, less attention has focused on the aggregate effects of
      regional increases in species richness as a result of human-mediated
      introductions. Here we examine several potential ecosystem consequences of
      increasing exotic species diversity of suspension feeding marine invertebrates.
      First, we experimentally manipulated native and non-native suspension feeder
      richness and measured its effect on short-term phytoplankton clearance rates.
      Multispecies communities all performed similarly, regardless of whether they were
      dominated by natives, exotics, or an even mix of the two. Individual species
      varied considerably in filtration rates, but non-native species often filtered
      less than the most similar native. Second, we determined potential changes in
      integrated function over time by comparing seasonal patterns of recruitment as a
      proxy for the ability to quickly recover filtration capacity after a disturbance.
      We found that exotic species have complementary seasonal phenologies both to
      native species and each other. Our results suggest that the consequences of local
      increases in species richness due to invasions may be manifest over long (annual
      to interannual) time scales, even when short term changes in ecosystem function
      are negligible.

PMID- 19580589
TI  - On the idea that analysts should acknowledge to their patients that they have
      failed them: a clinical debate. An introduction.

PMID- 19580588
TI  - Are specialists at risk under environmental change? Neoecological,
      paleoecological and phylogenetic approaches.
AB  - The question 'what renders a species extinction prone' is crucial to biologists.
      Ecological specialization has been suggested as a major constraint impeding the
      response of species to environmental changes. Most neoecological studies indicate
      that specialists suffer declines under recent environmental changes. This was
      confirmed by many paleoecological studies investigating longer-term survival.
      However, phylogeneticists, studying the entire histories of lineages, showed that
      specialists are not trapped in evolutionary dead ends and could even give rise to
      generalists. Conclusions from these approaches diverge possibly because (i) of
      approach-specific biases, such as lack of standardization for sampling efforts
      (neoecology), lack of direct observations of specialization (paleoecology), or
      binary coding and prevalence of specialists (phylogenetics); (ii) neoecologists
      focus on habitat specialization; (iii) neoecologists focus on extinction of
      populations, phylogeneticists on persistence of entire clades through periods of
      varying extinction and speciation rates; (iv) many phylogeneticists study species
      in which specialization may result from a lack of constraints. We recommend
      integrating the three approaches by studying common datasets, and accounting for
      range-size variation among species, and we suggest novel hypotheses on why
      certain specialists may not be particularly at risk and consequently why certain
      generalists deserve no less attention from conservationists than specialists.

PMID- 19580590
TI  - A relational psychoanalysis perspective on the necessity of acknowledging failure
      in order to restore the facilitating and containing features of the
      intersubjective relationship (the shared third).

PMID- 19580593
TI  - Looking back, looking forward: a reexamination of Benjamin Wolstein's interlock
      and the emergence of intersubjectivity.
AB  - In this paper the author takes a close look at Benjamin Wolstein's chapter,
      'Therapy', from his book, Countertransference, published in 1959. This chapter
      contains a discussion of what he refers to as the interlock between analyst and
      patient, or today what we might describe as transference/countertransference
      enactment. The author shows how Wolstein's concept of the interlock and its
      relation to the analyst's countertransference was radical and innovative for its
      time. Wolstein's notion of a transference/countertransference interlock, along
      with the seminal contributions of Ferenczi and some of the early interpersonal
      theorists, anticipates the complexities of a two-person psychology and the
      entanglement which can occur from the intermingling of unconscious processes of
      analyst and patient in the experiential field. The author highlights three main
      ideas. First, the author provides a brief review of enactment with an emphasis on
      the role of the analyst's participation as conceptualized by the various
      theoretical perspectives. An historical context is given for Wolstein's clinical
      theorizing. Second, the author explicates Wolstein's concept of the interlock,
      with particular attention to the processes involved which account for the
      complexities it presents. Third, the author examines the 'working through'
      process, including the emergence of intersubjectivity in the resolution of the
      interlock. The author shows throughout Wolstein's emphasis on the influence of
      the analyst's personal psychology, mutuality, and intersubjectivity, all of which
      anticipated the gradual interpersonalization of psychoanalysis across the various
      schools of thought.

PMID- 19580594
TI  - The 'body-container': a new perspective on the 'body-ego'.
AB  - Psychoanalytic theory and practice tend to focus on metaphorical and symbolic
      mental representations in a way that often pushes aside the importance of a
      bodily 'presence' possessing qualities that can not and should not be
      subordinated to the representational structure. By introducing the 'body
      container' model, this paper reintroduces the concrete physical body into the
      psychoanalytic discourse in a more direct way. This clinical-theoretical model
      links the 'body-ego' (Freud, 1923) to the container idea (Bion, 1962) aiming to
      creates a new integrative psyche-soma scheme. The 'body-container' experience is
      available as a subjective realization through a priori psycho-physical forms
      structured as an envelope and a central vertical axis. These forms are the
      outcome of our given bodily structure experienced under the 'magnetic' force of
      object relation. The mental envelope is already discussed in psychoanalytic
      theory (Anzieu, 1989, 1990; Bick, 1968) and I wish to introduce the
      characteristics of the vertical axis which I call 'the frontal spine',
      emphasizing its constitutional reciprocity with the skin envelope. The proposed
      model offers new insights into the psycho-physical organization in primitive
      mental states and may contribute to the understanding of the complementary
      structural relation between embodied and represented in human experience. Two
      clinical examples illustrate the therapeutic work relevant to disturbances in the
      primal psycho-physical space organization at different developmental levels.

PMID- 19580595
TI  - A confusion of tongues between psychoanalysis and philosophy: is the controversy
      over drive versus relational theory a philosophical one?
AB  - In recent years the controversy over Drive versus Relational models of the psyche
      has become entangled in a philosophical controversy over epistemology. Some have
      argued that the Drive model was a relic of an age of positivistic science, while
      Relational models are a product of a postmodern condition. This paper argues that
      the controversy need not be a philosophical one, and that Relational views are
      not, in fact, a product of postmodernism, nor are they necessarily dependent on a
      postmodern epistemology. Separating the epistemological from the psychological
      more carefully may help return the debate to its proper, psychoanalytic domain,
      and perhaps contribute to a more fruitful dialogue across what, at times, seems
      like an abyss between Relational views and Drive theory.

PMID- 19580596
TI  - Symmetric frenzy and catastrophic change: a consideration of primitive mental
      states in the wake of Bion and Matte Blanco.
AB  - The author explores the connections between Matte Blanco's notion of symmetric
      frenzy, i.e. the turbulence characteristic of the deepest levels of mental
      functioning, and Bion's concept of catastrophic change. For Bion, mental links
      are retrieved from the formless darkness of infinity. With catastrophic change,
      emotional violence and the confining nature of representation come into conflict,
      leaving the subject prey to an explosiveness that paralyses mental resources.
      Matte Blanco identifies indivisibility as the abyss in which all differentiation
      ceases; he bases his model on the conflict between symmetry and asymmetry.
      Infinity, he maintains, is where the first forms of mentalization develop. Both
      Bion and Matte Blanco emphasize the contrast between the immensity of mental
      space and the spatio-temporal order introduced by the activation of thinking
      functions. The author presents clinical material from the analysis of a psychotic
      patient, stressing the need to encourage both working through the defect of
      thinking (Bion) and 'unfolding' manifestations of symmetry (Matte Blanco) so as
      to foster the activation of the resources of thought, meanwhile postponing
      transference interpretation. He concludes with two later sessions, in which
      recognition of the analyst in the transference allows the analysand to develop
      his capacity for containment and asymmetric differentiation.

PMID- 19580597
TI  - The relevance of castration and circumcision to the origins of psychoanalysis: 1.
      The medical context.
AB  - In this paper the author outlines and discusses the origins and the decline of
      castration and circumcision as a cure for the nervous and psychic disturbances in
      women and little girls between 1875 and 1905. The author argues that the
      opposition to this medical practice affected the conception of hysteria,
      promoting a distinction between sexuality and the genital organs, and the
      emergence of an enlarged notion of sexuality, during the period from Freud's
      medical education to the publication of the Three Essays on the Theory of
      Sexuality. The hypothesis is put forward that Freud came directly in contact with
      the genital theory of the neurosis at the time of his training on the nervous
      disturbances in children with the paediatrician, Adolf Baginsky, in Berlin, in
      March 1886. It is hypothesized that this experience provoked in Freud an
      abhorrence of circumcision 'as a cure or punishment for masturbation', prompting
      an inner confrontation which resulted in a radical reorganization of the way of
      thinking about sexuality. It is also suggested that this contributed to Freud
      developing a capacity to stay with contradictions, something which would become a
      central quality of the psychoanalytic attitude.

PMID- 19580598
TI  - The ironic detachment of Edward Gibbon.
AB  - Edward Gibbon, the author of The History of the Decline and Fall of the Roman
      Empire, has been widely recognized as a master of irony. The historian's early
      life with parents he found self-serving and unreliable, his reaction to the
      events surrounding the death of his mother at the age of 9 and the decline of his
      father, left an impact on his personality and played a role in determining his
      choice of his life work. Irony has been approached from a psychoanalytic
      perspective as a mode of communication, as a stylistic device, as a modality
      through which one might view reality and as a way of uncovering the linkage
      between pretense and aspiration, between the apparent and the real. Gibbon's
      ironic detachment can be understood as rooted in his life history. He felt
      detached from his family of origin, in need of a protective device which would
      enable him to deal with passion. Sexual and aggressive impulses mobilized
      defensive postures that were later transformed into an attitude of skepticism and
      an interest in undercutting false beliefs and irrational authority, positions he
      attributes to religious ideation which served to instigate historical decline.

PMID- 19580599
TI  - 'The healing power of love': the literary/analytic bond of marriage in Freud's
      essay on Gradiva.
AB  - Freud 's declared position regarding the management of 'transference love'
      advocated 'abstinence', objectivity and even 'emotional coldness in the analyst'.
      However, his essay on Jensen's Gradiva reveals an identification with an involved
      and responsive 'maternal' analytic position associated with theorists such as
      Ferenczi, Balint and Winnicott. These theorists attribute the origins of
      transference love to the pre-oedipal stage, shaping their analytic model on the
      basis of the early relationship with the mother. Freud generally had difficulty
      identifying with such a position, since it entailed addressing his own inner
      feminine aspects. Yet a literary analysis of his 'Gradiva' reveals this stance in
      his textual performance, i.e. in the ways in which he reads and retells Jensen's
      story. Freud 's narration not only expresses identification with Zoe, the female
      protagonist, but also idealizes her 'therapeutic' conduct, which is closer in
      spirit to that of object-relations theorists. His subtext even implies, however
      unintended, that an ideal treatment of transference love culminates in a
      psychical 'marriage' bond between the analytic couple, a metaphor used by
      Winnicott to describe the essence of the mother-baby (analyst/patient) bond.
      Freud 's reading process is itself analogous to Zoe's 'therapeutic' conduct, in
      that both perform a creative and involved interaction with the text/patient.

PMID- 19580600
TI  - On boredom: a close encounter with encapsulated parts of the psyche.
AB  - The psychoanalytical literature has numerous scattered references to the
      analyst's experience of boredom, especially amongst writers working with
      primitive mental states. In the present paper, the author tries to gather some of
      these references in an attempt to integrate the various facets of this widespread
      phenomenon, and reflect on some clinical issues and dilemmas it raises. It is
      suggested that the experience of boredom in analysis may be a reaction to an
      encounter with a hidden, encapsulated part of the psyche, a bidimensional area of
      experience in which mental activity has been suspended, and experience remains
      meaningless. This is a barren area of lack, an encounter with the autistic core
      of the psyche. However, boredom may also be an experiential expression of
      despair, a re-living of primitive object relations with an emotionally non
      existent primary object. Through bringing the emptiness and desolation into
      analysis, the individual makes room for the empty, blunt, dead inner object which
      resides within him, and that needs to be integrated into the psyche. This inner
      object is a vital part of the patient's inner world, part of his history, and can
      neither be erased nor filled in order to eradicate the emptiness. This is
      illustrated by clinical material from patients along the spectrum of autism,
      autistic reaction following trauma and autistic barriers in neurotic patients.

PMID- 19580601
TI  - On: The mother in the text: metapsychology and fantasy in the work of
      interpretation.

PMID- 19580603
TI  - On: Leaps of faith: Is forgiveness a useful concept?

PMID- 19580605
TI  - On: Leaps of faith: Is forgiveness a useful concept?

PMID- 19580607
TI  - The skin house: a psychoanalytic reading of 3-Iron.

PMID- 19580608
TI  - A note on Mafia movies.

PMID- 19580616
TI  - Measurement for improvement: getting one to follow the other.

PMID- 19580617
TI  - Potential for methotrexate exposure through contamination during parenteral use
      as an immunosuppressant.
AB  - BACKGROUND: To evaluate whether the risk of methotrexate (MTX) exposure through
      skin contamination using parenteral doses of 25 mg warrants special oncology
      handling precautions during administration. METHODS: We conducted a study with
      six human volunteers deliberately exposed to an entire dose of 25 mg MTX solution
      on their skin for 30 min. Serum levels of MTX were measured at baseline, 2, 4, 8,
      12 and 24 h as well as serum homocysteine at baseline and 24 h after clinical
      exposure. Twenty-four-hour urinary excretion of MTX and possible local or
      systemic signs of toxicity were also recorded. RESULTS: All MTX serum
      concentrations were less than 0.02 micromol/L within the 24-h period. This is 500
      times below the recommended serum concentration for which folinic acid
      supplementation is recommended. There was also no significant increase in
      homocysteine level to suggest MTX toxicity. The only adverse effects were mild
      local dermal reactions in three female volunteers. CONCLUSION: Deliberate skin
      contamination and possible inhalation of a 25 mg MTX solution failed to show
      significant or quantifiable serum and urine concentrations to suggest MTX
      toxicity. Precautions to prevent contact with MTX designed for oncology protocols
      are unnecessary for our rheumatology patients or their carers using these much
      lower immunosuppressant doses for autoimmune diseases.

PMID- 19580618
TI  - What are the most effective strategies for improving quality and safety of health
      care?
AB  - There is now a plethora of different quality improvement strategies (QIS) for
      optimizing health care, some clinician/patient driven, others manager/policy
      maker driven. Which of these are most effective remains unclear despite expressed
      concerns about potential for QIS-related patient harm and wasting of resources.
      The objective of this study was to review published literature assessing the
      relative effectiveness of different QIS. Data sources comprising PubMed Clinical
      Queries, Cochrane Library and its Effective Practice and Organization of Care
      database, and HealthStar were searched for studies of QIS between January 1985
      and February 2008 using search terms based on an a priori QIS classification
      suggested by experts. Systematic reviews of controlled trials were selected in
      determining effect sizes for specific QIS, which were compared as a narrative
      meta-review. Clinician/patient driven QIS were associated with stronger evidence
      of efficacy and larger effect sizes than manager/policy-maker driven QIS. The
      most effective strategies (>10% absolute increase in appropriate care or
      equivalent measure) included clinician-directed audit and feedback cycles,
      clinical decision support systems, specialty outreach programmes, chronic disease
      management programmes, continuing professional education based on interactive
      small-group case discussions, and patient-mediated clinician reminders. Pay-for
      performance schemes directed to clinician groups and organizational process
      redesign were modestly effective. Other manager/policy-maker driven QIS including
      continuous quality improvement programmes, risk and safety management systems,
      public scorecards and performance reports, external accreditation, and clinical
      governance arrangements have not been adequately evaluated with regard to
      effectiveness. QIS are heterogeneous and methodological flaws in much of the
      evaluative literature limit validity and generalizability of results. Based on
      current best available evidence, clinician/patient driven QIS appear to be more
      effective than manager/policy-maker driven QIS although the latter have, in many
      instances, attracted insufficient robust evaluations to accurately determine
      their comparative effectiveness.

PMID- 19580619
TI  - Aspirin for primary prevention: do potential benefits outweigh the risks?
AB  - The role of aspirin for primary prevention in healthy individuals has been the
      subject of clinical trials for more than a quarter of a century. Because of this
      evidence, or sometimes despite it, many individuals self-administer aspirin to
      prevent cardiovascular events. This article reviews the published work for
      aspirin in primary prevention of cardiovascular and malignant diseases and
      considers whether aspirin would be approved by regulatory authorities for this
      use if it were to be marketed for this indication today.

PMID- 19580620
TI  - Central nervous system is a sanctuary site for chronic myelogenous leukaemia
      treated with imatinib mesylate.
AB  - Imatinib mesylate (IM) is currently used as the first therapeutic choice against
      chronic myelogenous leukaemia (CML). Because IM poorly penetrates the blood-brain
      barrier, IM-treated CML patients may have a potential risk of central nervous
      system (CNS) involvement. Here we report a case with lymphoid blast crisis
      isolated only in CNS after bacterial meningitis, although the patient achieved
      and maintained complete cytogenetic response by IM therapy. It is important to
      consider isolated CNS blast crisis as a possible event in IM-treated CML
      patients.

PMID- 19580621
TI  - Comparison of the MMSE and RUDAS cognitive screening tools in an elderly
      inpatient population in everyday clinical use.
AB  - We compared test score and performance times of Folstein's Mini Mental State
      Examination (MMSE) and the Rowland Universal Dementia Assessment Scale (RUDAS).
      Forty-six patients were recruited. The mean score was 20.6 for the MMSE and 20.5
      for the RUDAS. Linear regression analysis revealed an r value of 0.83 (P < 0.05).
      The mean performance time was 9.4 min for both the MMSE and the RUDAS. Patient
      satisfaction was similar for both tests. Surveyed clinicians preferred the MMSE
      because of greater familiarity. We concluded that the RUDAS correlates well with
      the MMSE and is no more time-consuming to perform. It has good clinical utility
      as a cognitive screening tool.

PMID- 19580622
TI  - Hypercalcaemia caused by a carcinoid tumour.
AB  - Humoral hypercalcaemia resulting from carcinoid tumours is uncommon. We report a
      case of hypercalcaemia because of excessive secretion of parathyroid hormone
      related protein (PTHrP) in a 77-year-old woman with an advanced carcinoid tumour.
      Fibroblast growth factor 23 levels were also elevated. The hypercalcaemia
      responded to adjunctive therapy with long-acting octreotide analogue therapy,
      bisphosphonates and steroids. The role of PTHrP in humoral hypercalcaemia of
      malignancy, its association with neuroendocrine tumours, as well as the
      therapeutic use of somatostatin analogues are reviewed.

PMID- 19580623
TI  - The saddle sign.

PMID- 19580624
TI  - Oxaliplatin-induced transient ischaemic attack.

PMID- 19580625
TI  - Multiple myeloma complicated by Evans syndrome.

PMID- 19580626
TI  - Mimicking myocardial infarction: localized ST-segment elevation in Campylobacter
      jejuni myopericarditis.

PMID- 19580633
TI  - Active matrix metalloproteinase-2 promotes apoptosis of hepatic stellate cells
      via the cleavage of cellular N-cadherin.
AB  - BACKGROUND AND AIMS: Hepatic stellate cells (HSC) are known to synthesise excess
      matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the
      matrix-degrading matrix metalloproteinase enzymes (MMPs) and their tissue
      inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis,
      the expression of TIMP-1 declines and hepatic collagenolytic activity increases.
      This is accompanied by HSC apoptosis. In this study, we examine a potential
      mechanism whereby MMP activity might induce HSC apoptosis by cleaving N-cadherin
      at the cell surface. RESULTS: N-cadherin expression was upregulated in human HSC
      during activation in culture. Addition of function-blocking antibodies or a
      peptide targeting the extracellular domain of N-cadherin, to cultured HSC,
      promoted apoptosis. During apoptosis, there was cleavage of N-cadherin into 20
      100 kDa fragments. MMP-2 became activated early during HSC apoptosis and directly
      cleaved N-cadherin in vitro. Addition of activated MMP-2 to HSCs in culture
      resulted in enhanced apoptosis and loss of N-cadherin. CONCLUSIONS: Together,
      these studies identify a role for both N-cadherin and MMP-2 in mediating HSC
      apoptosis, where N-cadherin works to provide a cell survival stimulus and MMP-2
      promotes HSC apoptosis concomitant with N-cadherin degradation.

PMID- 19580634
TI  - Factors associated with treatment failure of patients with psychiatric diseases
      and injecting drug users in the treatment of genotype 2 or 3 hepatitis C chronic
      infection.
AB  - BACKGROUND: Genotype 2/3 hepatitis C virus (HCV) has a good response to treatment
      with peginterferon and ribavirin. Patients with psychiatric disorders and
      injecting drug users (IDUs) are considered 'difficult to treat' and are often
      excluded from treatment despite the lack of evidence supporting this decision.
      AIMS: To investigate the outcome and factors associated with treatment failure in
      these groups. METHODS: This is an observational study of a cohort of patients
      infected by genotype 2/3 HCV. IDUs and patients with psychiatric diseases were
      not excluded from treatment. We performed an intention-to-treat analysis to
      evaluate factors related to treatment failure. RESULTS: A sustained virological
      response (SVR) was achieved in 91 of the 125 patients treated (72.8%). Patients
      with chronic psychotic disorders or former IDUs had SVR rates similar to other
      groups. After multivariate analysis, independent factors associated with
      treatment failure were liver cirrhosis [odds ratio (OR) 3.4, 95% confidence
      interval (CI) 1.1-10.4], a history of depression and not being on antidepressants
      at the commencement of HCV treatment (OR 4.4, 95% CI 1.2-16) and active IDUs (OR
      7.3, 95% CI 1.77-30.4). CONCLUSIONS: Patients with a history of depression who
      were not receiving antidepressants and active IDUs are more likely to fail
      treatment for genotype 2/3 HCV and will need additional support.

PMID- 19580636
TI  - Obesity is not a choice.

PMID- 19580635
TI  - A novel mutation in the biliverdin reductase-A gene combined with liver cirrhosis
      results in hyperbiliverdinaemia (green jaundice).
AB  - BACKGROUND: Hyperbiliverdinaemia is a poorly defined clinical sign that has been
      infrequently reported in cases of liver cirrhosis or liver carcinoma, usually
      indicating a poor long-term prognosis. AIMS: To clarify the pathogenesis of
      hyperbiliverdinaemia in an extended case report. METHODS: A 64-year-old man with
      alcoholic cirrhosis was admitted to hospital with severe bleeding from
      oesophageal varices. Ultrasonography showed ascites, but no dilatation of the
      biliary tree. The skin, sclerae, plasma, urine and ascites of the patient showed
      a greenish appearance. Bilirubin levels were normal, and there were no signs of
      haemolysis. Biliverdin was analysed in plasma and urine with liquid
      chromatography coupled to mass spectrometry. The seven exonic regions of the
      biliverdin reductase-A (BVR-A) gene was amplified by polymerase chain reaction
      and sequenced. RESULTS: Biliverdin was present in plasma and urine. In nucleotide
      52 of exon I of the DNA isolated from the hyperbiliverdinaemic patient, we
      discovered a novel heterozygous C-->T nonsense mutation converting an arginine
      (CGA) in position 18 into a stop codon (TGA) (R18Stop) predicted to truncate the
      protein N-terminally to the active site Tyr97. Two children of the proband were
      heterozygous for the identical mutation in the BVR-A gene, but had no clinical
      signs of liver disease and had normal levels of biliverdin. The BVR-A gene
      mutation was not found in 200 healthy volunteers or nine patients with end-stage
      liver cirrhosis. CONCLUSION: Hyperbiliverdinaemia (green jaundice) with green
      plasma and urine may be caused by a genetic defect in the BVR-A gene in
      conjunction with decompensated liver cirrhosis.

PMID- 19580640
TI  - Abstracts of the 6th Metabolic Syndrome Symposium, 8-12 April 2009, Antalya,
      Turkey.

PMID- 19580641
TI  - Regulation of TGF-beta signalling by Fbxo11, the gene mutated in the Jeff otitis
      media mouse mutant.
AB  - BACKGROUND: Jeff is a dominant mouse mutant displaying chronic otitis media. The
      gene underlying Jeff is Fbxo11, a member of the large F-box family, which are
      specificity factors for the SCF E3 ubiquitin ligase complex. Jeff homozygotes die
      shortly after birth displaying a number of developmental abnormalities including
      cleft palate and eyes open at birth. TGF-beta signalling is involved in a number
      of epithelial developmental processes and we have investigated the impact of the
      Jeff mutation on the expression of this pathway. RESULTS: Phospho-Smad2 (pSmad2)
      is significantly upregulated in epithelia of Jeff homozygotes. Moreover, there
      was a significant increase in nuclear localization of pSmad2 in contrast to wild
      type. Mice heterozygous for both Jeff and Smad2 mutations recapitulate many of
      the features of the Jeff homozygous phenotype. However, tissue
      immunoprecipitations failed to detect any interaction between Fbxo11 and Smad2.
      Fbxo11 is known to neddylate p53, a co-factor of pSmad2, but we did not find any
      evidence of genetic interactions between Jeff and p53 mutants. Nevertheless, p53
      levels are substantially reduced in Jeff mice suggesting that Fbxo11 plays a role
      in stabilizing p53. CONCLUSION: Overall, our findings support a model whereby
      Fbxo11, possibly via stabilization of p53, is required to limit the accumulation
      of pSmad2 in the nucleus of epithelial cells of palatal shelves, eyelids and
      airways of the lungs. The finding that Fbxo11 impacts upon TGF-beta signalling
      has important implications for our understanding of the underlying disease
      mechanisms of middle ear inflammatory disease.

PMID- 19580642
TI  - Against pragmatism: on efficacy, effectiveness and the real world.
AB  - Explanatory and pragmatic trials represent ends of a continuum of attitudes about
      clinical trial design. Recent literature argues that pragmatic trials are more
      informative about clinical care in the real world. Although there is place for
      more pragmatic studies to inform clinical practice and health policy decision
      making, we are concerned that it is generally under-appreciated that
      extrapolating the results of broadly inclusive pragmatic trials to the care of
      real patients may often be as problematic as extrapolating the results of
      narrowly focused explanatory or efficacy trials. Simplistic interpretation of
      pragmatic trials runs the risk of driving harmful policies.

PMID- 19580643
TI  - Esophagopericardial fistula as a rare complication after total gastrectomy for
      cancer.
AB  - BACKGROUND: Esophagopericardial fistula is a rare but life-threatening
      complication of benign, malignant or traumatic esophageal disease. It is most
      commonly associated with benign etiology and carries a high mortality rate which
      increases with delay in diagnosis. CASE PRESENTATION: We present a case of an
      esophagopericardial fistula as a rare complication in a 53-year-old male patient,
      7 months after total gastrectomy for an adenocarcinoma of the esophagogastric
      junction. CONCLUSION: The prognosis of esophagopericardial fistula is poor,
      especially when it is associated with malignancy.

PMID- 19580644
TI  - Enzymatic hydrolysis of steam-pretreated lignocellulosic materials with
      Trichoderma atroviride enzymes produced in-house.
AB  - BACKGROUND: Improvement of the process of cellulase production and development of
      more efficient lignocellulose-degrading enzymes are necessary in order to reduce
      the cost of enzymes required in the biomass-to-bioethanol process. RESULTS:
      Lignocellulolytic enzyme complexes were produced by the mutant Trichoderma
      atroviride TUB F-1663 on three different steam-pretreated lignocellulosic
      substrates, namely spruce, wheat straw and sugarcane bagasse. Filter paper
      activities of the enzymes produced on the three materials were very similar,
      while beta-glucosidase and hemicellulase activities were more dependent on the
      nature of the substrate. Hydrolysis of the enzyme preparations investigated
      produced similar glucose yields. However, the enzymes produced in-house proved to
      degrade the xylan and the xylose oligomers less efficiently than a commercial
      mixture of cellulase and beta-glucosidase. Furthermore, accumulation of xylose
      oligomers was observed when the TUB F-1663 supernatants were applied to xylan
      containing substrates, probably due to the low beta-xylosidase activity of the
      enzymes. The efficiency of the enzymes produced in-house was enhanced by
      supplementation with extra commercial beta-glucosidase and beta-xylosidase. When
      the hydrolytic capacities of various mixtures of a commercial cellulase and a T.
      atroviride supernatant produced in the lab were investigated at the same enzyme
      loading, the glucose yield appeared to be correlated with the beta-glucosidase
      activity, while the xylose yield seemed to be correlated with the beta-xylosidase
      level in the mixtures. CONCLUSION: Enzyme supernatants produced by the mutant T.
      atroviride TUB F-1663 on various pretreated lignocellulosic substrates have good
      filter paper activity values combined with high levels of beta-glucosidase
      activities, leading to cellulose conversion in the enzymatic hydrolysis that is
      as efficient as with a commercial cellulase mixture. On the other hand, in order
      to achieve good xylan conversion, the supernatants produced by the mutant have to
      be supplemented with additional beta-xylosidase activity.

PMID- 19580645
TI  - Assessment of environmental correlates of physical activity: development of a
      European questionnaire.
AB  - BACKGROUND: Research on the influence of the physical environment on physical
      activity is rapidly expanding and different measures of environmental perceptions
      have been developed, mostly in the US and Australia. The purpose of this paper is
      to (i) provide a literature review of measures of environmental perceptions
      recently used in European studies and (ii) develop a questionnaire for population
      monitoring purposes in the European countries. METHODS: This study was done
      within the framework of the EU-funded project 'Instruments for Assessing Levels
      of Physical Activity and Fitness (ALPHA)', which aims to propose standardised
      instruments for physical activity and fitness monitoring across Europe.
      Quantitative studies published from 1990 up to November 2007 were systematically
      searched in Pubmed, Web of Science, TRIS and Geobase. In addition a survey was
      conducted among members of the European network for the promotion of Health
      Enhancing Physical Activity (HEPA Europe) and European members of the
      International Physical Activity and Environment Network (IPEN) to identify
      published or ongoing studies. Studies were included if they were conducted among
      European general adult population (18+y) and used a questionnaire to assess
      perceptions of the physical environment. A consensus meeting with an
      international expert group was organised to discuss the development of a European
      environmental questionnaire. RESULTS: The literature search resulted in 23
      European studies, 15 published and 8 unpublished. In these studies, 13 different
      environmental questionnaires were used. Most of these studies used adapted
      versions of questionnaires that were developed outside Europe and that focused
      only on the walkability construct: The Neighborhood Environment Walkability Scale
      (NEWS), the abbreviated version of the NEWS (ANEWS) and the Neighborhood Quality
      of Life Study (NQLS) questionnaire have been most commonly used. Based on the
      results of the literature review and the output of the meeting with international
      experts, a European environmental questionnaire with 49 items was developed.
      CONCLUSION: There is need for a greater degree of standardization in
      instruments/methods used to assess environmental correlates of physical activity,
      taking into account the European-specific situation. A first step in this process
      is taken by the development of a European environmental questionnaire.

PMID- 19580646
TI  - Pesticide-related illness reported to and diagnosed in primary care: implications
      for surveillance of environmental causes of ill-health.
AB  - BACKGROUND: In Great Britain (GB), data collected on pesticide associated illness
      focuses on acute episodes such as poisonings caused by misuse or abuse. This
      study aimed to investigate the extent and nature of pesticide-related illness
      presented and diagnosed in Primary Care and the feasibility of establishing a
      routine monitoring system. METHODS: A checklist, completed by General
      Practitioners (GP) for all patients aged 18+ who attended surgery sessions,
      identified patients to be interviewed in detail on exposures and events that
      occurred in the week before their symptoms appeared. RESULTS: The study covered
      59320 patients in 43 practices across GB and 1335 detailed interviews. The annual
      incidence of illness reported to GPs because of concern about pesticide exposure
      was estimated to be 0.04%, potentially 88400 consultations annually,
      approximately 1700 per week. The annual incidence of consultations where symptoms
      were diagnosed by GPs as likely to be related to pesticide exposure was 0.003%,
      an annual estimate of 6630 consultations i.e. about 128 per week. 41% of
      interviewees reported using at least one pesticide at home in the week before
      symptoms occurred. The risk of having symptoms possibly related to pesticide
      exposure compared to unlikely was associated with home use of pesticides after
      adjusting for age, gender and occupational pesticide exposure (OR = 1.88, 95% CI
      1.51 - 2.35). CONCLUSION: GP practices were diverse and well distributed
      throughout GB with similar symptom consulting patterns as in the Primary Care
      within the UK. Methods used in this study would not be feasible for a routine
      surveillance system for pesticide related illness. Incorporation of environmental
      health into Primary Care education and practice is needed.

PMID- 19580647
TI  - Assessment of the medicinal potentials of the methanol extracts of the leaves and
      stems of Buddleja saligna.
AB  - BACKGROUND: Buddleja saligna Willd (Loganiaceae) is a small to medium-sized
      evergreen tree; trunk short, often gnarled and crooked; crown dense, rounded or
      domed-shaped; foliage greyish green. The wild olives are traditionally used to
      lower blood pressures in many parts of the world. In southern Africa, bark and
      leaf decoctions are used to treat colic, coughs, colds, sore eyes, urinary
      problems and as purgatives. METHODS: The antibacterial, antioxidant activities
      and phenolic contents of the methanol extracts of the leaves and stems of
      Buddleja saligna 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
      leaves and stem extracts of Buddleja saligna 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
      antioxidant activities of the leaves as determined by the ABTS and DPPH were
      similar to that of the stem. The flavonoids and the flavonols contents of the
      leaves were higher than that of the stem but the total phenols, proanthocyanidins
      and FRAP activities were higher in the methanol extracts of the stem. The
      extracts did show activity against both Gram-positive and Gram-negative bacteria.
      For instance, while the methanol extract of the leaves showed good activities on
      all the organisms except Serratia marcescens and Pseudomonas aeruginosa at MICs
      of between 2.5 and 5.0 mg/ml, the extract of the stem only showed activities on
      Bacillus cereus, Streptococcus pyrogens and Pseudomonas aeruginosa at the same
      concentration. CONCLUSION: The results from this study indicate that the leaves
      and stem extracts of Buddleja saligna possess antioxidant properties and could
      serve as free radical inhibitors or scavenger or, acting possibly as primary
      antioxidants. Although, the antibacterial properties of Buddleja saligna are not
      as effective as the standard drugs-Chloramphenicol and Streptomycin, they still
      possess some activity against bacterial strains used in this study. Buddleja
      saligna may therefore be a good candidate for functional foods as well as
      pharmaceutical plant-based products.

PMID- 19580648
TI  - Whole genome expression analysis within the angiotensin II-apolipoprotein E
      deficient mouse model of abdominal aortic aneurysm.
AB  - BACKGROUND: An animal model commonly used to investigate pathways and potential
      therapeutic interventions relevant to abdominal aortic aneurysm (AAA) involves
      subcutaneous infusion of angiotensin II within the apolipoprotein E deficient
      mouse. The aim of this study was to investigate genes differentially expressed in
      aneurysms forming within this mouse model in order to assess the relevance of
      this model to human AAA. RESULTS: Using microarrays we identified genes relevant
      to aneurysm formation within apolipoprotein E deficient mice. Firstly we
      investigated genes differentially expressed in the aneurysm prone segment of the
      suprarenal aorta in these mice. Secondly we investigated genes that were
      differentially expressed in the aortas of mice developing aneurysms relative to
      those that did not develop aneurysms in response to angiotensin II infusion. Our
      findings suggest that a host of inflammation and extracellular matrix remodelling
      pathways are upregulated within the aorta in mice developing aneurysms. Kyoto
      Encyclopedia of Genes and Genome categories enriched in the aortas of mice with
      aneurysms included cytokine-cytokine receptor interaction, leukocyte
      transendothelial migration, natural killer cell mediated cytotoxicity and
      hematopoietic cell lineage. Genes associated with extracellular matrix
      remodelling, such as a range of matrix metalloproteinases were also
      differentially expressed in relation to aneurysm formation. CONCLUSION: This
      study is the first report describing whole genome expression arrays in the
      apolipoprotein E deficient mice in relation to aneurysm formation. The findings
      suggest that the pathways believed to be critical in human AAA are also relevant
      to aneurysm formation in this mouse model. The findings therefore support the
      value of this model to investigate interventions and mechanisms of human AAA.

PMID- 19580649
TI  - Comparison of three methods of extravascular lung water volume measurement in
      patients after cardiac surgery.
AB  - INTRODUCTION: Measurement of extravascular lung water (EVLW) by using the lithium
      thermal (Li-thermal) and single-thermal indicator dilution methods was compared
      with the indocyanine green-thermal (ICG-thermal) method in humans. METHODS:
      Single-center observational study involving patients undergoing cardiac surgery
      with cardiopulmonary bypass. Paired measurements were taken 1, 2, 4, and 6 hours
      after surgery. Bland-Altman analysis was used to calculate bias and limits of
      agreement. Data are presented as mean (SD) or median (IQR). RESULTS: Seventeen
      patients were recruited (age, 69 years (54 to 87 years); Parsonnet score 10 (0 to
      29)). Sixteen ICG-thermal measurements were excluded after blinded assessment
      because of poor-quality indicator dilution curves. EVLW volume as measured by the
      ICG-thermal technique was 4.6 (1.9) ml/kg, compared with 5.3 (1.4) ml/kg for the
      single-thermal method. Measurements taken with the Li-thermal method were clearly
      erroneous (-7.6 (7.4) ml/kg). In comparison with simultaneous measurements with
      the ICG-thermal method, single-thermal measurements had an acceptable degree of
      bias, but limits of agreement were poor (bias, -0.3 ml/kg (2.3)). Li-thermal
      measurements compared poorly with the ICG-thermal reference method (bias, 13.2
      ml/kg (14.4)). CONCLUSIONS: The principal finding of this study was that the
      prototype Li-thermal method did not provide reliable measurements of EVLW volume
      when compared with the ICG-thermal reference technique. Although minimal bias was
      associated with the single-thermal method, limits of agreement were approximately
      45% of the normal value of EVLW volume. The Li-thermal method performed very
      poorly because of the overestimation of mean indicator transit time by using an
      external lithium ion electrode. These findings suggest that the assessment of
      lung water content by lithium-indicator dilution is not sufficiently reliable for
      clinical use in individual patients.

PMID- 19580650
TI  - Macrorheology of cystic fibrosis, chronic obstructive pulmonary disease & normal
      sputum.
AB  - BACKGROUND: Prior microrheologic assessments of selected, microlitre plugs of
      cystic fibrosis (CF) sputum suggest no intrinsic rheologic abnormality. However,
      such analyses may not be representative of CF sputum as a whole. We therefore
      reassessed this question using whole sputum macrorheology. Additionally, we
      wished to further explore the relationships between sputum rheology, inflammation
      and infection. METHODS: Dynamic oscillatory macrorheometry was performed on whole
      expectorated sputum from stable adults with CF (n = 18) and COPD (n = 12) and
      induced sputum from normal controls (n = 7). Concomitant sputum inflammatory
      mediator levels were measured in CF and COPD samples. Sputum collected from CF
      subjects (n = 6) at commencement and completion of intravenous antibiotic therapy
      for an infective exacerbation was also assessed. RESULTS: CF sputum neutrophil
      elastase activity (NE) was significantly related to degree of sputum purulence (p
      = 0.049) and correlated significantly with measures of sputum viscoelasticity (r
      = 0.696, p = 0.008 for storage modulus G' at 9 Hz). There were significant
      differences in viscoelasticity between subject groups when samples were compared
      irrespective of appearance/degree of sputum purulence. However, the macrorheology
      of mucoid CF sputum did not differ from normal sputum (eg median (range) G' at 9
      Hz 2.25 (0.79, 3.26) vs 2.04 (1.4,4.6) Pa, p = 1). In contrast, mucoid COPD
      samples demonstrated significantly greater viscoelasticity (G' at 9 Hz 4.5 (2.4,
      23) Pa) than sputum from both CF (p = 0.048) & normal subjects (p = 0.009).
      Antibiotic therapy during exacerbations was associated with significant
      reductions in CF sputum viscoelasticity, with mean (SD) G' at 9 Hz decreasing
      from 28.5 (11.5) Pa at commencement to 6.4 (4.6) Pa on day 7 (p = 0.01).
      CONCLUSION: The macrorheologic properties of whole, mucoid CF sputum are not
      different from normal, confirming the results of prior microrheologic studies.
      Instead, CF sputum viscoelasticity is related to secondary infection, decreases
      with intravenous antibiotic therapy and correlates with inflammation. In
      contrast, COPD sputum demonstrates inherently greater viscoelasticity, providing
      a novel target for potential therapeutic interventions.

PMID- 19580651
TI  - Unfractionated heparin and enoxaparin reduce high-stretch ventilation augmented
      lung injury: a prospective, controlled animal experiment.
AB  - INTRODUCTION: Dysregulation of coagulation and local fibrinolysis found in
      patients with acute lung injury often results in the need for the support of
      mechanical ventilation. High-tidal-volume mechanical ventilation can increase
      lung damage and suppression of fibrinolytic activity, but the mechanisms are
      unclear. We hypothesized that subcutaneous injections of unfractionated heparin
      and enoxaparin would decrease neutrophil infiltration, lung edema, and
      plasminogen-activator inhibitor-1 (PAI-1) production in mice exposed to high
      tidal-volume ventilation. METHODS: Male C57BL/6 mice, weighing 20 to 25 g, were
      exposed to either high-tidal-volume (30 ml/kg) or low-tidal-volume (6 ml/kg)
      mechanical ventilation with room air for 1 to 5 hours after 200 IU/kg or 400
      IU/kg unfractionated heparin and 4 mg/kg or 8 mg/kg enoxaparin administration.
      Nonventilated mice served as a control group. Evan blue dye, lung wet- to dry
      weight ratio, histopathologic grading of epithelium, myeloperoxidase, and gene
      expression of PAI-1 were measured. The expression of PAI-1 was studied by
      immunohistochemistry. RESULTS: High-tidal-volume ventilation induced increased
      microvascular permeability, neutrophil influx, PAI-1 mRNA expression, production
      of PAI-1 protein, and positive staining of PAI-1 in epithelium in a dose
      dependent manner. Lung injury induced by high-tidal-volume ventilation was
      attenuated with PAI-1-deficient mice and pharmacologic inhibition of PAI-1
      activity by low-dose unfractionated heparin and enoxaparin. CONCLUSIONS: We
      conclude that high-tidal-volume mechanical ventilation increased microvascular
      permeability, neutrophil influx, lung PAI-1 mRNA expression, production of active
      PAI-1. The deleterious effects were attenuated by low-dose unfractionated heparin
      or enoxaparin treatment. Understanding the protective mechanism of unfractionated
      heparin and enoxaparin related to the reduction of PAI-1 may afford further
      knowledge of the effects of mechanical forces in the lung and development of
      possible therapeutic strategies involved in acute lung injury.

PMID- 19580652
TI  - Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial
      dysfunction in septic rats.
AB  - INTRODUCTION: Increasing evidence indicates that epidural anesthesia improves
      postoperative pulmonary function. The underlying mechanisms, however, remain to
      be determined. Because pulmonary nitric oxide has been identified to play a
      critical role in pulmonary dysfunction in sepsis, we hypothesized that thoracic
      epidural anesthesia (TEA) modulates endothelial dysfunction via a nitric oxide
      dependent pathway. METHODS: Thirty-six Sprague-Dawley rats underwent sham
      laparotomy or induction of peritoneal sepsis caused by cecal ligation and
      puncture (CLP). Septic animals were then treated with either bupivacaine 0.5% or
      normal saline epidurally (15 microl/h-1) for 6 hours or 24 hours after injury.
      Previous experiments demonstrated that these time points correspond with a
      hyperdynamic (at 6 hours) and hypodynamic circulation (at 24 hours),
      respectively. In addition, two sham control groups received either bupivacaine
      0.5% or normal saline epidurally (15 microl/h-1). Six and 24 hours after injury,
      hemodynamic measurements and arterial blood gas analyses were performed in awake,
      spontaneously breathing rats. Exhaled nitric oxide, bradykinin-induced pulmonary
      vasoconstriction (a surrogate marker of endothelial dysfunction), pulmonary
      wet/dry-weight ratio (an estimate of pulmonary edema), and myeloperoxidase
      activity (MPO, a surrogate marker of neutrophil infiltration into lung tisssue)
      were investigated at 6 and 24 hours by using an established model of isolated and
      perfused lungs. RESULTS: In hyperdynamic sepsis, treatment with TEA resulted in
      reduced bradykinin-induced pulmonary vasoconstriction (P < 0.05) and lower levels
      of exhaled NO as compared with those in untreated septic rats (P < 0.05).
      However, the development of pulmonary edema or MPO activity in the lungs was not
      alleviated by sympathetic blockade in this phase of sepsis. Conversely, TEA led
      to an increased bradykinin-induced pulmonary vasoconstriction and pulmonary edema
      despite reduced exNO levels and pulmonary MPO activity in hypodynamic sepsis
      (each P < 0.05 versus CLP 24 h). Pulmonary gas exchange was only marginally
      affected under the influence of TEA in hypodynamic sepsis. Mean arterial pressure
      and heart rate were not affected beyond the changes caused by sepsis itself.
      CONCLUSIONS: The results of the present study suggest that TEA modulates the NO
      pathway and exerts positive effects on pulmonary endothelial integrity only in
      hyperdynamic sepsis. Whether the negative effects on endothelial function in
      hypodynamic sepsis have an impact on overall morbidity and mortality remains to
      be determined in future studies.

PMID- 19580653
TI  - Benefit of warm water immersion on biventricular function in patients with
      chronic heart failure.
AB  - BACKGROUND: Regular physical activity and exercise are well-known cardiovascular
      protective factors. Many elderly patients with heart failure find it difficult to
      exercise on land, and hydrotherapy (training in warm water) could be a more
      appropriate form of exercise for such patients. However, concerns have been
      raised about its safety.The aim of this study was to investigate, with
      echocardiography and Doppler, the acute effect of warm water immersion (WWI) and
      effect of 8 weeks of hydrotherapy on biventricular function, volumes and systemic
      vascular resistance. A secondary aim was to observe the effect of hydrotherapy on
      brain natriuretic peptide (BNP). METHODS: Eighteen patients [age 69 +/- 8 years,
      left ventricular ejection fraction 31 +/- 9%, peakVO2 14.6 +/- 4.5 mL/kg/min]
      were examined with echocardiography on land and in warm water (34 degrees
      C).Twelve of these patients completed 8 weeks of control period followed by 8
      weeks of hydrotherapy twice weekly. RESULTS: During acute WWI, cardiac output
      increased from 3.1 +/- 0.8 to 4.2 +/- 0.9 L/min, LV tissue velocity time integral
      from 1.2 +/- 0.4 to 1.7 +/- 0.5 cm and right ventricular tissue velocity time
      integral from 1.6 +/- 0.6 to 2.5 +/- 0.8 cm (land vs WWI, p < 0.0001,
      respectively). Heart rate decreased from 73 +/- 12 to 66 +/- 11 bpm (p < 0.0001),
      mean arterial pressure from 92 +/- 14 to 86 +/- 16 mmHg (p < 0.01), and systemic
      vascular resistance from 31 +/- 7 to 22 +/- 5 resistant units (p < 0.0001).There
      was no change in the cardiovascular response or BNP after 8 weeks of
      hydrotherapy. CONCLUSION: Hydrotherapy was well tolerated by all patients. The
      main observed cardiac effect during acute WWI was a reduction in heart rate,
      which, together with a decrease in afterload, resulted in increases in systolic
      and diastolic biventricular function. Although 8 weeks of hydrotherapy did not
      improve cardiac function, our data support the concept that exercise in warm
      water is an acceptable regime for patients with heart failure.

PMID- 19580654
TI  - Cardiovascular magnetic resonance guided electrophysiology studies.
AB  - Catheter ablation is a first line treatment for many cardiac arrhythmias and is
      generally performed under x-ray fluoroscopy guidance. However, current techniques
      for ablating complex arrhythmias such as atrial fibrillation and ventricular
      tachycardia are associated with suboptimal success rates and prolonged radiation
      exposure. Pre-procedure 3D CMR has improved understanding of the anatomic basis
      of complex arrhythmias and is being used for planning and guidance of ablation
      procedures. A particular strength of CMR compared to other imaging modalities is
      the ability to visualize ablation lesions. Post-procedure CMR is now being
      applied to assess ablation lesion location and permanence with the goal of
      indentifying factors leading to procedure success and failure. In the future,
      intra-procedure real-time CMR, together with the ability to image complex 3-D
      arrhythmogenic anatomy and target additional ablation to regions of incomplete
      lesion formation, may allow for more successful treatment of even complex
      arrhythmias without exposure to ionizing radiation. Development of clinical grade
      CMR compatible electrophysiology devices is required to transition intra
      procedure CMR from pre-clinical studies to more routine use in patients.

PMID- 19580655
TI  - Oncolytic vaccinia therapy of squamous cell carcinoma.
AB  - BACKGROUND: Novel therapies are necessary to improve outcomes for patients with
      squamous cell carcinomas (SCC) of the head and neck. Historically, vaccinia virus
      was administered widely to humans as a vaccine and led to the eradication of
      smallpox. We examined the therapeutic effects of an attenuated, replication
      competent vaccinia virus (GLV-1h68) as an oncolytic agent against a panel of six
      human head and neck SCC cell lines. RESULTS: All six cell lines supported viral
      transgene expression (beta-galactosidase, green fluorescent protein, and
      luciferase) as early as 6 hours after viral exposure. Efficient transgene
      expression and viral replication (>150-fold titer increase over 72 hrs) were
      observed in four of the cell lines. At a multiplicity of infection (MOI) of 1,
      GLV-1h68 was highly cytotoxic to the four cell lines, resulting in > or = 90%
      cytotoxicity over 6 days, and the remaining two cell lines exhibited >45%
      cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated
      >60% cell death over 6 days. A single injection of GLV-1h68 (5 x 10(6) pfu)
      intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral
      luciferase activity peaking at days 2-4, with gradual resolution over 10 days and
      no evidence of spread to normal organs. Treated animals exhibited near-complete
      tumor regression over a 24-day period without any observed toxicity, while
      control animals demonstrated rapid tumor progression. CONCLUSION: These results
      demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for
      infecting and lysing head and neck SCC both in vitro and in vivo, and support its
      continued investigation in future clinical trials.

PMID- 19580656
TI  - DDEC: Dragon database of genes implicated in esophageal cancer.
AB  - BACKGROUND: Esophageal cancer ranks eighth in order of cancer occurrence. Its
      lethality primarily stems from inability to detect the disease during the early
      organ-confined stage and the lack of effective therapies for advanced-stage
      disease. Moreover, the understanding of molecular processes involved in
      esophageal cancer is not complete, hampering the development of efficient
      diagnostics and therapy. Efforts made by the scientific community to improve the
      survival rate of esophageal cancer have resulted in a wealth of scattered
      information that is difficult to find and not easily amendable to data-mining. To
      reduce this gap and to complement available cancer related bioinformatic
      resources, we have developed a comprehensive database (Dragon Database of Genes
      Implicated in Esophageal Cancer) with esophageal cancer related information, as
      an integrated knowledge database aimed at representing a gateway to esophageal
      cancer related data. DESCRIPTION: Manually curated 529 genes differentially
      expressed in EC are contained in the database. We extracted and analyzed the
      promoter regions of these genes and complemented gene-related information with
      transcription factors that potentially control them. We further, precompiled text
      mined and data-mined reports about each of these genes to allow for easy
      exploration of information about associations of EC-implicated genes with other
      human genes and proteins, metabolites and enzymes, toxins, chemicals with
      pharmacological effects, disease concepts and human anatomy. The resulting
      database, DDEC, has a useful feature to display potential associations that are
      rarely reported and thus difficult to identify. Moreover, DDEC enables inspection
      of potentially new 'association hypotheses' generated based on the precompiled
      reports. CONCLUSION: We hope that this resource will serve as a useful complement
      to the existing public resources and as a good starting point for researchers and
      physicians interested in EC genetics. DDEC is freely accessible to academic and
      non-profit users at http://apps.sanbi.ac.za/ddec/. DDEC will be updated twice a
      year.

PMID- 19580657
TI  - The chemiluminescence based Ziplex automated workstation focus array reproduces
      ovarian cancer Affymetrix GeneChip expression profiles.
AB  - BACKGROUND: As gene expression signatures may serve as biomarkers, there is a
      need to develop technologies based on mRNA expression patterns that are adaptable
      for translational research. Xceed Molecular has recently developed a Ziplex
      technology, that can assay for gene expression of a discrete number of genes as a
      focused array. The present study has evaluated the reproducibility of the Ziplex
      system as applied to ovarian cancer research of genes shown to exhibit distinct
      expression profiles initially assessed by Affymetrix GeneChip analyses. METHODS:
      The new chemiluminescence-based Ziplex gene expression array technology was
      evaluated for the expression of 93 genes selected based on their Affymetrix
      GeneChip profiles as applied to ovarian cancer research. Probe design was based
      on the Affymetrix target sequence that favors the 3' UTR of transcripts in order
      to maximize reproducibility across platforms. Gene expression analysis was
      performed using the Ziplex Automated Workstation. Statistical analyses were
      performed to evaluate reproducibility of both the magnitude of expression and
      differences between normal and tumor samples by correlation analyses, fold change
      differences and statistical significance testing. RESULTS: Expressions of 82 of
      93 (88.2%) genes were highly correlated (p < 0.01) in a comparison of the two
      platforms. Overall, 75 of 93 (80.6%) genes exhibited consistent results in normal
      versus tumor tissue comparisons for both platforms (p < 0.001). The fold change
      differences were concordant for 87 of 93 (94%) genes, where there was agreement
      between the platforms regarding statistical significance for 71 (76%) of 87
      genes. There was a strong agreement between the two platforms as shown by
      comparisons of log2 fold differences of gene expression between tumor versus
      normal samples (R = 0.93) and by Bland-Altman analysis, where greater than 90% of
      expression values fell within the 95% limits of agreement. CONCLUSION: Overall
      concordance of gene expression patterns based on correlations, statistical
      significance between tumor and normal ovary data, and fold changes was consistent
      between the Ziplex and Affymetrix platforms. The reproducibility and ease-of-use
      of the technology suggests that the Ziplex array is a suitable platform for
      translational research.

PMID- 19580658
TI  - Prevalence of obsessive-compulsive disorder in Turkish university students and
      assessment of associated factors.
AB  - BACKGROUND: Many students who begin university at risky periods for OCD
      development cannot meet the new challenges successfully. They often seek help and
      apply to the university health center for psychiatric distress. We aimed to
      determine the prevalence and associated factors of Obsessive Compulsive Disorder
      (OCD) at students of the Cukurova University in this cross sectional study.
      METHODS: This study was performed in the Cukurova University Faculty of Education
      with a population of 5500 students; the representative sample size for detecting
      the OCD prevalence was calculated to be 800. After collecting sociodemographic
      data, we questioned the students for associated factors of OCD. The General
      Health Questionnaire-12 (GHQ-12) and Composite International Diagnostic Interview
      (CIDI, Section K) were used for psychiatric evaluation. Logistic regression
      analysis was performed to evaluate the linkage between OCD and associated
      factors. RESULTS: A total of 804 university students were included in this study.
      The GHQ-12-positive students (241 students, 29.9%) were interviewed using Section
      K of the CIDI (222 students, 27.6%). OCD was diagnosed in 33 (4.2%) students. The
      Logistic regression analysis of the data showed significant associations between
      OCD and male gender (p:0.036), living on government dormitory (p: 0.003), living
      on students' house/parental house (p:0.006), having private room in the parental
      house (p:0.055) and verbal abuse in the family (p:0.006). CONCLUSION: This study
      demonstrates a higher prevalence of OCD among a group of university students
      compared to other prevalence studies of OCD in Turkish society. Furthermore, our
      findings also suggest relationships between OCD and sociodemographic factors, as
      well as other environmental stress factors.

PMID- 19580659
TI  - Discovery of novel targets for multi-epitope vaccines: screening of HIV-1 genomes
      using association rule mining.
AB  - BACKGROUND: Studies have shown that in the genome of human immunodeficiency virus
      (HIV-1) regions responsible for interactions with the host's immune system,
      namely, cytotoxic T-lymphocyte (CTL) epitopes tend to cluster together in
      relatively conserved regions. On the other hand, "epitope-less" regions or
      regions with relatively low density of epitopes tend to be more variable.
      However, very little is known about relationships among epitopes from different
      genes, in other words, whether particular epitopes from different genes would
      occur together in the same viral genome. To identify CTL epitopes in different
      genes that co-occur in HIV genomes, association rule mining was used. RESULTS:
      Using a set of 189 best-defined HIV-1 CTL/CD8+ epitopes from 9 different protein
      coding genes, as described by Frahm, Linde & Brander (2007), we examined the
      complete genomic sequences of 62 reference HIV sequences (including 13 subtypes
      and sub-subtypes with approximately 4 representative sequences for each subtype
      or sub-subtype, and 18 circulating recombinant forms). The results showed that
      despite inclusion of recombinant sequences that would be expected to break-up
      associations of epitopes in different genes when two different genomes are
      recombined, there exist particular combinations of epitopes (epitope
      associations) that occur repeatedly across the world-wide population of HIV-1.
      For example, Pol epitope LFLDGIDKA is found to be significantly associated with
      epitopes GHQAAMQML and FLKEKGGL from Gag and Nef, respectively, and this
      association rule is observed even among circulating recombinant forms.
      CONCLUSION: We have identified CTL epitope combinations co-occurring in HIV-1
      genomes including different subtypes and recombinant forms. Such co-occurrence
      has important implications for design of complex vaccines (multi-epitope
      vaccines) and/or drugs that would target multiple HIV-1 regions at once and,
      thus, may be expected to overcome challenges associated with viral escape.

PMID- 19580660
TI  - Evidence for a role of NTS2 receptors in the modulation of tonic pain
      sensitivity.
AB  - BACKGROUND: Central neurotensin (NT) administration results in a naloxone
      insensitive antinociceptive response in animal models of acute and persistent
      pain. Both NTS1 and NTS2 receptors were shown to be required for different
      aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors
      were extensively associated with ascending nociceptive pathways, both at the
      level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found
      that spinally administered NTS2-selective agonists induced dose-dependent
      antinociceptive responses in the acute tail-flick test. In the present study, we
      therefore investigated whether activation of spinal NTS2 receptors suppressed the
      persistent inflammatory pain symptoms observed after intraplantar injection of
      formalin. RESULTS: We first demonstrated that spinally administered NT and NT69L
      agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain
      evoked responses during the inflammatory phase of the formalin test. Accordingly,
      pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was
      effective in inhibiting the aversive behaviors induced by formalin. With
      resolution at the single-cell level, we also found that activation of spinal NTS2
      receptors reduced formalin-induced c-fos expression in dorsal horn neurons.
      However, our results also suggest that NTS2-selective agonists and NTS1/NTS2
      mixed compounds differently modulated the early (21-39 min) and late (40-60 min)
      tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at
      different levels of the central nervous system. Indeed, while non-selective drugs
      suppressed pain-related behaviors activity in both part of phase 2, intrathecal
      injection of NTS2-selective agonists was only efficient in reducing pain during
      the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of
      lifting, shaking, licking and biting to formalin also revealed that unlike non
      discriminative NTS1/NTS2 analogs reversing all nociceptive endpoint behaviors,
      pure NTS2 agonists specifically inhibited paw lifting, supporting a role of NTS2
      in spinal modulation of persistent nociception. CONCLUSION: The present study
      provides the first demonstration that activation of NTS2 receptors produces
      analgesia in the persistent inflammatory pain model of formalin. The dichotomy
      between these two classes of compounds also indicates that both NTS1 and NTS2
      receptors are involved in tonic pain inhibition and implies that these two NT
      receptors modulate the pain-induced behavioral responses by acting on distinct
      spinal and/or supraspinal neural circuits. In conclusion, development of NT
      agonists targeting both NTS1 and NTS2 receptors could be useful for chronic pain
      management.

PMID- 19580661
TI  - Disagreements with implications: diverging discourses on the ethics of non
      medical use of methylphenidate for performance enhancement.
AB  - BACKGROUND: There is substantial evidence that methylphenidate (MPH; Ritalin), is
      being used by healthy university students for non-medical motives such as the
      improvement of concentration, alertness, and academic performance. The scope and
      potential consequences of the non-medical use of MPH upon healthcare and society
      bring about many points of view. METHODS: To gain insight into key ethical and
      social issues on the non-medical use of MPH, we examined discourses in the print
      media, bioethics literature, and public health literature. RESULTS: Our study
      identified three diverging paradigms with varying perspectives on the nature of
      performance enhancement. The beneficial effects of MPH on normal cognition were
      generally portrayed enthusiastically in the print media and bioethics discourses
      but supported by scant information on associated risks. Overall, we found a
      variety of perspectives regarding ethical, legal and social issues related to the
      non-medical use of MPH for performance enhancement and its impact upon social
      practices and institutions. The exception to this was public health discourse
      which took a strong stance against the non-medical use of MPH typically viewed as
      a form of prescription abuse or misuse. Wide-ranging recommendations for
      prevention of further non-medical use of MPH included legislation and increased
      public education. CONCLUSION: Some positive portrayals of the non-medical use of
      MPH for performance enhancement in the print media and bioethics discourses could
      entice further uses. Medicine and society need to prepare for more prevalent non
      medical uses of neuropharmaceuticals by fostering better informed public debates.

PMID- 19580662
TI  - Ascending aortic aneurysm in a patient with bicuspid aortic valve, positive
      history of systemic autoimmune diseases and common genetic factors: a case
      report.
AB  - The bicuspid aortic valve (BAV) and specific systemic autoimmune diseases are
      associated with cardiovascular manifestation, including aortic aneurysm. We
      reported a case of 64 year-old patient with BAV and a history of ankylosing
      spondylitis (AS) and systemic lupus erythematosus (SLE), and who developed
      ascending thoracic aortic aneurysm. The patient presented also the homozygosity
      for genetic variants of MMP9, ACE, MTHFR and PAI-1 genes. Gene-environmental
      interactions may represent an additional pathogenetic dimension in the still
      challenging management of the abnormalities of the aortic wall, including
      dilatation, aneurysm and dissection.

PMID- 19580663
TI  - Comparative evaluation of four mosquitoes sampling methods in rice irrigation
      schemes of lower Moshi, northern Tanzania.
AB  - BACKGROUND: Adult malaria vector sampling is the most important parameter for
      setting up an intervention and understanding disease dynamics in malaria endemic
      areas. The intervention will ideally be species-specific according to sampling
      output. It was the objective of this study to evaluate four sampling techniques,
      namely human landing catch, pit shelter, indoor resting collection and odour
      baited entry trap. METHODOLOGY: These four sampling methods were evaluated
      simultaneously for thirty days during October 2008, a season of low mosquitoes
      density and malaria transmission. These trapping methods were performed in one
      village for maximizing homogeneity in mosquito density. The cattle and man used
      in odour-baited entry trap were rotated between the chambers to avoid bias.
      RESULTS: A total of 3,074 mosquitoes were collected. Among these 1,780 (57.9%)
      were Anopheles arabiensis and 1,294 (42.1%) were Culex quinquefasciatus. Each
      trap sampled different number of mosquitoes, Indoor resting collection collected
      335 (10.9%), Odour-baited entry trap-cow 1,404 (45.7%), Odour-baited entry trap
      human 378 (12.3%), Pit shelter 562 (18.3%) and HLC 395 (12.8%). General linear
      model univariate analysis method was used, position of the trapping method had no
      effect on mosquito density catch (DF = 4, F = 35.596, P = 0.78). Days variation
      had no effect on the collected density too (DF = 29, F = 4.789, P = 0.09). The
      sampling techniques had significant impact on the caught mosquito densities (DF =
      4, F = 34.636, P < 0.0001). The Wilcoxon pair-wise comparison between mosquitoes
      collected in human landing catch and pit shelter was significant (Z = -3.849, P <
      0.0001), human landing catch versus Indoor resting collection was not significant
      (Z = -0.502, P = 0.615), human landing catch versus odour-baited entry trap-man
      was significant (Z = -2.687, P = 0.007), human landing catch versus odour-baited
      entry trap-cow was significant (Z = -3.127, P = 0.002). CONCLUSION: Odour-baited
      traps with different baits and pit shelter have shown high productivity in
      collecting higher densities of mosquitoes than human landing catch. These
      abilities are the possibilities of replacing the human landing catch practices
      for sampling malaria vectors in areas with An. arabiensis as malaria vectors.
      Further evaluations of these sampling methods need to be investigated is other
      areas with different species.

PMID- 19580664
TI  - High-resolution ultrasound biomicroscopy for monitoring ovarian structures in
      mice.
AB  - BACKGROUND: Until recently, the limit of spatial resolution of ultrasound systems
      has prevented characterization of structures <1 mm. Hence, the study of ovarian
      follicular development in rodents has been based on one-time histological
      examination of excised tissues; i.e., longitudinal study of day-to-day ovarian
      changes has not been possible in mice and rats. The objective was to establish an
      ultrasonographic approach to study follicular and luteal dynamics in mice and
      rats. METHODS: Experiment 1 was a pilot study to develop methods of
      immobilization (physical restraint vs. general anesthesia) and determine
      technical factors affecting ovarian images using ultrasound bio-microscopy in
      rats vs. mice. The hair coat was removed over the thoraco-lumber area using
      depilation cream, and a highly viscous acoustic gel was applied while the animals
      were maintained in sternal recumbency. In Experiment 2, changes in ovarian
      structures during the estrous cycle were monitored by twice daily ultrasonography
      in 10 mice for 2 estrous cycles. RESULTS: Ovarian images were not distinct in
      rats due to attenuation of ultrasound waves. Physical restraint, without general
      anesthesia, was insufficient for immobilization in mice. By placing the
      transducer face over the dorsal flank, the kidney was visualized initially as a
      point of reference. A routine of moving the transducer a few millimetres caudo
      laterally from the kidney was established to quickly and consistently localize
      the ovaries; the total time to scan both ovaries in a mouse was about 10 minutes.
      By comparing vaginal cytology with non-anesthetized controls, repeated exposure
      to anesthesia did not affect the estrous cycle. Temporal changes in the number of
      follicles in 3 different size categories support the hypothesis that follicles
      >/= 20 microns develop in a wave-like fashion. CONCLUSION: The mouse is a
      suitable model for the study of ovarian dynamics using transcutaneous ultrasound
      bio-microscopy. Repeated general anesthesia for examination had no apparent
      effect on the estrous cycle, and preliminary results revealed a wave-like pattern
      of ovarian follicle development in mice.

PMID- 19580666
TI  - Interviewee Transcript Review: assessing the impact on qualitative research.
AB  - BACKGROUND: This paper assesses interviewee transcript review (ITR) as a
      technique for improving the rigour of interview-based, qualitative research. ITR
      is a process whereby interviewees are provided with verbatim transcripts of their
      interviews for the purposes of verifying accuracy, correcting errors or
      inaccuracies and providing clarifications. ITR, in various forms, is widely used
      among qualitative researchers, however there is limited methodological guidance
      on how it should be employed and little is known about its actual impact on the
      transcript, the data, the interviewee or the researcher. METHODS: ITR was
      incorporated into a qualitative research study in which 51 key informant
      interviews were conducted with a range of senior stakeholders within the Canadian
      health care system. The changes made by interviewees to their transcripts were
      systematically tracked and categorized using a set of mutually exclusive
      categories. RESULTS: The study found that ITR added little to the accuracy of the
      transcript and may create complications if the goal of the researcher is to
      produce a transcript which reflects precisely what was said at the time of the
      interview. The advantages of ITR are that it allows interviewees the opportunity
      to edit or clarify information provided in the original interview, with many
      interviewees providing corrections, clarifications, and in some cases, adding new
      material to their transcripts. There are also potential disadvantages, such as a
      bias created by inconsistent data sources or the loss of data when an interviewee
      chooses to remove valuable material. The impact of ITR on the interviewee may be
      both positive and negative, depending on the specific circumstances and the
      nature of the study. The impact of ITR on the researcher was minimal in this
      study, but is again subject to specific circumstances of the research context.
      CONCLUSION: While ITR is employed by many researchers across numerous fields, the
      advantages of its use may be relatively small in terms of verifying the accuracy
      of qualitative interview transcripts. Researchers are advised to carefully
      consider both the potential advantages and disadvantages of ITR outlined in this
      paper before deciding to incorporate the practice within their qualitative study
      designs.

PMID- 19580667
TI  - Extraneural metastases from cranial meningioma: a case report.
AB  - Extracranial metastases from brain meningiomas is a rare, but well-documented
      entity. Metastases occur mostly in the lungs, pleura and liver, but may also
      affect lymph nodes and bones. We report here on a patient who was treated for an
      atypical brain meningioma with multiple surgeries and multiple sessions of
      stereotactic radiosurgery with good control of his brain disease. Thirteen years
      after diagnosis, he developed bilateral large sacroiliac and abdominal
      metastases.

PMID- 19580665
TI  - Stopping randomized trials early for benefit: a protocol of the Study Of Trial
      Policy Of Interim Truncation-2 (STOPIT-2).
AB  - BACKGROUND: Randomized clinical trials (RCTs) stopped early for benefit often
      receive great attention and affect clinical practice, but pose interpretational
      challenges for clinicians, researchers, and policy makers. Because the decision
      to stop the trial may arise from catching the treatment effect at a random high,
      truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of
      Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the
      epidemiology and reporting quality of tRCTs, found that such trials are becoming
      more common, but that reporting of stopping rules and decisions were often
      deficient. Most importantly, treatment effects were often implausibly large and
      inversely related to the number of the events accrued. The aim of STOPIT-2 is to
      determine the magnitude and determinants of possible bias introduced by stopping
      RCTs early for benefit. METHODS/DESIGN: We will use sensitive strategies to
      search for systematic reviews addressing the same clinical question as each of
      the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will
      check all RCTs included in each systematic review to determine their similarity
      to the index tRCT in terms of participants, interventions, and outcome
      definition, and conduct new meta-analyses addressing the outcome that led to
      early termination of the tRCT. For each pair of tRCT and systematic review of
      corresponding non-tRCTs we will estimate the ratio of relative risks, and hence
      estimate the degree of bias. We will use hierarchical multivariable regression to
      determine the factors associated with the magnitude of this ratio. Factors
      explored will include the presence and quality of a stopping rule, the
      methodological quality of the trials, and the number of total events that had
      occurred at the time of truncation.Finally, we will evaluate whether Bayesian
      methods using conservative informative priors to "regress to the mean"
      overoptimistic tRCTs can correct observed biases. DISCUSSION: A better
      understanding of the extent to which tRCTs exaggerate treatment effects and of
      the factors associated with the magnitude of this bias can optimize trial design
      and data monitoring charters, and may aid in the interpretation of the results
      from trials stopped early for benefit.

PMID- 19580668
TI  - EBV-positive diffuse large B-cell lymphoma in a human T-lymphotropic virus type 1
      carrier.
AB  - The development of B-cell lymphomas has been seldom described in HTLV-1 carriers.
      We present the case of an elderly Peruvian HTLV-1 carrier who was diagnosed with
      EBV-positive diffuse large B-cell lymphoma. Despite an initial good response to
      therapy, patient died during treatment due to fatal Pneumocystis jirovecci
      pneumonia. EBV infection is characterized by B-cell lymphotropism and selective
      immunodeficiency. HTLV-1, on the other hand, induces T-cell dysfunction and B
      cell proliferation. Finally, immunosenescence is characterized by T-cell
      dysregulation, decreased apoptosis and cytokine upregulation. In this elderly
      patient, the combination of EBV and HTLV-1 coinfection and immunosenescence may
      have played a role in the development of this aggressive diffuse large B-cell
      lymphoma. Furthermore, the immunodeficiency caused by the viral infections and
      chemotherapy may have played a role in developing life-threatening infectious
      complications.

PMID- 19580669
TI  - Prediction of localization and interactions of apoptotic proteins.
AB  - During apoptosis several mitochondrial proteins are released. Some of them
      participate in caspase-independent nuclear DNA degradation, especially apoptosis
      inducing factor (AIF) and endonuclease G (endoG). Another interesting protein,
      which was expected to act similarly as AIF due to the high sequence homology with
      AIF is AIF-homologous mitochondrion-associated inducer of death (AMID). We
      studied the structure, cellular localization, and interactions of several
      proteins in silico and also in cells using fluorescent microscopy. We found the
      AMID protein to be cytoplasmic, most probably incorporated into the cytoplasmic
      side of the lipid membranes. Bioinformatic predictions were conducted to analyze
      the interactions of the studied proteins with each other and with other possible
      partners. We conducted molecular modeling of proteins with unknown 3D structures.
      These models were then refined by MolProbity server and employed in molecular
      docking simulations of interactions. Our results show data acquired using a
      combination of modern in silico methods and image analysis to understand the
      localization, interactions and functions of proteins AMID, AIF, endonuclease G,
      and other apoptosis-related proteins.

PMID- 19580671
TI  - High quality RNA from multiple brain regions simultaneously acquired by laser
      capture microdissection.
AB  - BACKGROUND: Laser capture microdissection enables the isolation of single cells
      or small cell groups from histological sections under direct microscopic
      observation. Combined with quantitative PCR or microarray, it is a very powerful
      approach for studying gene expression profiles in discrete cell populations. The
      major challenge for such studies is to obtain good quality RNA from small amounts
      of starting material. RESULTS: We have developed a simple, flexible, and low-cost
      method for simultaneously producing RNA from discrete cell groups in embryonic
      day 15 mouse brain. In particular, we have optimized the following key steps in
      the procedure: staining, cryosectioning, storage of sections and harvesting of
      microdissected cells. We obtained the best results when staining 20 mum-thick
      sections with 1% cresyl violet in 70% ethanol and harvesting the microdissected
      tissue in RNA stabilization solution. In addition, we introduced three stop
      points in the protocol which makes the tedious process of laser capture
      microdissection more flexible, without compromising RNA quality. CONCLUSION:
      Using this optimized method, we have consistently obtained RNA of high quality
      from all four simultaneously microdissected cell groups. RNA integrity numbers
      were all above 8, and long cDNA fragments (> 1.2 kb) were successfully amplified
      by reverse transcription PCR from all four samples. We conclude that RNAs
      isolated by this method are well suited for downstream quantitative PCR or
      microarray studies.

PMID- 19580670
TI  - Identification, functional characterization and developmental regulation of
      sesquiterpene synthases from sunflower capitate glandular trichomes.
AB  - BACKGROUND: Sesquiterpene lactones are characteristic metabolites of Asteraceae
      (or Compositae) which often display potent bioactivities and are sequestered in
      specialized organs such as laticifers, resin ducts, and trichomes. For
      characterization of sunflower sesquiterpene synthases we employed a simple method
      to isolate pure trichomes from anther appendages which facilitated the
      identification of these genes and investigation of their enzymatic functions and
      expression patterns during trichome development. RESULTS: Glandular trichomes of
      sunflower (Helianthus annuus L.) were isolated, and their RNA was extracted to
      investigate the initial steps of sesquiterpene lactone biosynthesis. Reverse
      transcription-PCR experiments led to the identification of three sesquiterpene
      synthases. By combination of in vitro and in vivo characterization of
      sesquiterpene synthase gene products in Escherichia coli and Saccharomyces
      cerevisiae, respectively, two enzymes were identified as germacrene A synthases,
      the key enzymes of sesquiterpene lactone biosynthesis. Due to the very low in
      vitro activity, the third enzyme was expressed in vivo in yeast as a thioredoxin
      fusion protein for functional characterization. In in vivo assays, it was
      identified as a multiproduct enzyme with the volatile sesquiterpene hydrocarbon
      delta-cadinene as one of the two main products with alpha-muuorlene, beta
      caryophyllene, alpha-humulene and alpha-copaene as minor products. The second
      main compound remained unidentified. For expression studies, glandular trichomes
      from the anther appendages of sunflower florets were isolated in particular
      developmental stages from the pre- to the post-secretory phase. All three
      sesquiterpene synthases were solely upregulated during the biosynthetically
      active stages of the trichomes. Expression in different aerial plant parts
      coincided with occurrence and maturity of trichomes. Young roots with root hairs
      showed expression of the sesquiterpene synthase genes as well. CONCLUSION: This
      study functionally identified sesquiterpene synthase genes predominantly
      expressed in sunflower trichomes. Evidence for the transcriptional regulation of
      sesquiterpene synthase genes in trichome cells suggest a potential use for these
      specialized cells for the identification of further genes involved in the
      biosynthesis, transport, and regulation of sesquiterpene lactones.

PMID- 19580672
TI  - Ultraviolet-ozone treatment reduces levels of disease-associated prion protein
      and prion infectivity.
AB  - BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are a group of fatal
      neurodegenerative diseases caused by novel infectious agents referred to as
      prions. Prions appear to be composed primarily, if not exclusively, of a
      misfolded isoform of the cellular prion protein. TSE infectivity is remarkably
      stable and can resist many aggressive decontamination procedures, increasing
      human, livestock and wildlife exposure to TSEs. FINDINGS: We tested the
      hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein
      and inactivates the infectious agent. We found that UV-ozone treatment decreased
      the carbon and prion protein content in infected brain homogenate to levels
      undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After
      8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated
      material by a factor of at least 105. A small amount of infectivity, however,
      persisted despite UV-ozone treatment. When bound to either montmorillonite clay
      or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone.
      CONCLUSION: Our findings strongly suggest that UV-ozone treatment can degrade
      pathogenic prion protein and inactivate prions, even when the agent is associated
      with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with
      other decontaminant methods may allow the sterilization of TSE-contaminated
      materials.

PMID- 19580673
TI  - The limited usefulness of real-time 3-dimensional echocardiography in obtaining
      normal reference ranges for right ventricular volumes.
AB  - BACKGROUND: To obtain normal reference ranges and intraobserver variability for
      right ventricular (RV) volume indexes (VI) and ejection fraction (EF) from apical
      recordings with real-time 3-dimensional echocardiography (RT3DE), and similarly
      for RV area indexes (AI) and area fraction (AF) with 2-dimensional
      echocardiography (2DE). METHODS: 166 participants; 79 males and 87 females aged
      between 29-79 years and considered free from clinical and subclinical
      cardiovascular disease. Normal ranges are defined as 95% reference values and
      reproducibility as coefficients of variation (CV) for repeated measurements.
      RESULTS: None of the apical recordings with RT3DE and 2DE included the RV outflow
      tract. Upper reference values were 62 ml/m2 for RV end-diastolic (ED) VI and 24
      ml/m2 for RV end-systolic (ES) VI. Lower normal reference value for RVEF was 41%.
      The respective reference ranges were 17 cm2/m2 for RVEDAI, 11 cm2/m2 for RVESAI
      and 27% for RVAF. Males had higher upper normal values for RVEDVI, RVESVI and
      RVEDAI, and a lower limit than females for RVEF and RVAF. Weak but significant
      negative correlations between age and RV dimensions were found with RT3DE, but
      not with 2DE. CVs for repeated measurements ranged between 10% and 14% with RT3DE
      and from 5% to 14% with 2DE. CONCLUSION: Although the normal ranges for RVVIs and
      RVAIs presented in this study reflect RV inflow tract dimensions only, the data
      presented may still be regarded as a useful tool in clinical practice, especially
      for RVEF and RVAF.

PMID- 19580674
TI  - The impact of itch symptoms in psoriasis: results from physician interviews and
      patient focus groups.
AB  - BACKGROUND: The objective of this qualitative study was to better understand the
      impact of psoriasis symptoms using a 3-part process: 1) develop a disease model
      for psoriasis to identify the most important concepts relevant to psoriasis
      patients; 2) conduct interviews with dermatologists to identify key areas of
      clinical concern; and 3) explore psoriasis patients' perceptions of the impact of
      psoriasis. METHODS: A disease model was developed from a review of the published
      literature and later revised based on the findings of clinician interviews and
      patient focus groups. To confirm the clinical relevance of the concepts
      identified in the disease model, 5 dermatologists were selected and interviewed
      one-on-one. They were asked to rate major psoriasis symptoms according to
      importance and bothersomeness level to patients on separate scales of 1 to 10.
      Results of clinician interviews were used to develop interview guides for patient
      focus groups. To identify important domains of psoriasis, 39 patients
      participated in 5 separate concept elicitation focus groups. Four focus groups
      included patients with severe psoriasis (n = 31) and one included patients with
      mild psoriasis (n = 8). Patients were asked to describe their current psoriasis
      symptoms and to rate them on a scale of 1 to 10, according to importance,
      severity, and troublesomeness. An average mean rating was calculated for each
      symptom throughout all focus groups. RESULTS: Clinicians most frequently
      mentioned itch (n = 5), psoriatic arthritis or "joint pains" (n = 4), flaking (n
      = 4), and pain (n = 3) as primary physical symptoms of psoriasis. Three
      clinicians gave a rating of 10 for the importance of itch; two clinicians gave
      ratings of 8 and 7 for importance. The majority of patients rated itch as the
      most important (31/39), most severe (31/39), and most troublesome (24/39) symptom
      and noted that itch negatively impacted daily activities (eg, concentration,
      sleep, ability to attend work or school), as well as emotions (eg, anxiety and
      embarrassment). CONCLUSION: These analyses suggest that itch is one of the most
      important symptoms of psoriasis, contributing to diminished health-related
      quality of life (HRQoL) in patients with both mild and severe disease.

PMID- 19580675
TI  - Pathological studies on postvaccinal reactions of Rift Valley fever in goats.
AB  - RVF live attenuated vaccine (Smithburn strain) was evaluated by using goats as
      experimental animal. The results indicate that this vaccine cause severe
      deleterious pathological changes in liver especially in kids and causing abortion
      in pregnant does. The virus was seen to be propagated inside hepatic cells
      forming intranuclear inclusions which was also seen by E.M. Viral antigens were
      detected in hepatic cells, gall bladder, endothelial lining of blood vessels,
      leukocytes, kidneys and heart by using immunoflourescent technique. It could be
      concluded that the use of live attenuated vaccine of RVF (Smithburn strain) for
      immunization of live stock is not safe in Egypt as it considered an endemic area.

PMID- 19580676
TI  - Test-retest variability of high resolution positron emission tomography (PET)
      imaging of cortical serotonin (5HT2A) receptors in older, healthy adults.
AB  - BACKGROUND: Position emission tomography (PET) imaging using [18F]-setoperone to
      quantify cortical 5-HT2A receptors has the potential to inform pharmacological
      treatments for geriatric depression and dementia. Prior reports indicate a
      significant normal aging effect on serotonin 5HT2A receptor (5HT2AR) binding
      potential. The purpose of this study was to assess the test-retest variability of
      [18F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT2AR
      availability in subjects greater than 60 years old. METHODS: Six healthy subjects
      (age range = 65-78 years) completed two [18F]-setoperone PET scans on two
      separate occasions 5-16 weeks apart. RESULTS: The average difference in the
      binding potential (BPND) as measured on the two occasions in the frontal and
      temporal cortical regions ranged between 2 and 12%, with the lowest intraclass
      correlation coefficient in anterior cingulate regions. CONCLUSION: We conclude
      that the test-retest variability of [18F]-setoperone PET in elderly subjects is
      comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger
      subject samples.

PMID- 19580677
TI  - Deep sampling of the Palomero maize transcriptome by a high throughput strategy
      of pyrosequencing.
AB  - BACKGROUND: In-depth sequencing analysis has not been able to determine the
      overall complexity of transcriptional activity of a plant organ or tissue sample.
      In some cases, deep parallel sequencing of Expressed Sequence Tags (ESTs),
      although not yet optimized for the sequencing of cDNAs, has represented an
      efficient procedure for validating gene prediction and estimating overall gene
      coverage. This approach could be very valuable for complex plant genomes. In
      addition, little emphasis has been given to efforts aiming at an estimation of
      the overall transcriptional universe found in a multicellular organism at a
      specific developmental stage. RESULTS: To explore, in depth, the transcriptional
      diversity in an ancient maize landrace, we developed a protocol to optimize the
      sequencing of cDNAs and performed 4 consecutive GS20-454 pyrosequencing runs of a
      cDNA library obtained from 2 week-old Palomero Toluqueno maize plants. The
      protocol reported here allowed obtaining over 90% of informative sequences. These
      GS20-454 runs generated over 1.5 Million reads, representing the largest amount
      of sequences reported from a single plant cDNA library. A collection of 367,391
      quality-filtered reads (30.09 Mb) from a single run was sufficient to identify
      transcripts corresponding to 34% of public maize ESTs databases; total sequences
      generated after 4 filtered runs increased this coverage to 50%. Comparisons of
      all 1.5 Million reads to the Maize Assembled Genomic Islands (MAGIs) provided
      evidence for the transcriptional activity of 11% of MAGIs. We estimate that 5.67%
      (86,069 sequences) do not align with public ESTs or annotated genes, potentially
      representing new maize transcripts. Following the assembly of 74.4% of the reads
      in 65,493 contigs, real-time PCR of selected genes confirmed a predicted
      correlation between the abundance of GS20-454 sequences and corresponding levels
      of gene expression. CONCLUSION: A protocol was developed that significantly
      increases the number, length and quality of cDNA reads using massive 454 parallel
      sequencing. We show that recurrent 454 pyrosequencing of a single cDNA sample is
      necessary to attain a thorough representation of the transcriptional universe
      present in maize, that can also be used to estimate transcript abundance of
      specific genes. This data suggests that the molecular and functional diversity
      contained in the vast native landraces remains to be explored, and that large
      scale transcriptional sequencing of a presumed ancestor of the modern maize
      varieties represents a valuable approach to characterize the functional diversity
      of maize for future agricultural and evolutionary studies.

PMID- 19580679
TI  - Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis,
      poor prognosis, and regulation of CXCR4 expression.
AB  - BACKGROUND: Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth
      factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an
      important role in lymph node metastasis of various human cancers, including
      breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting
      tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor
      metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic
      CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer
      2008,8:340; Breast Cancer Res Treat 2005, 91:125-132). METHODS: The relationship
      between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4
      expression, and other established clinicopathological variables (these data were
      cited in our previous papers), including prognosis, was analyzed in human breast
      cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and
      chemotaxis were assessed in MDA-MB-231 breast cancer cells. RESULTS: Nrp2
      expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas.
      Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C
      expression, and cytoplasmic CXCR4 expression. Survival curves determined by the
      Kaplan-Meier method showed that Nrp2 expression was associated with reduced
      overall survival. In multivariate analysis, Nrp2 expression emerged as a
      significant independent predictor for overall survival. Neutralizing anti-Nrp2
      antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA
      MB-231 cells. CONCLUSION: Nrp2 expression was correlated with lymph node
      metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression
      may serve as a significant prognostic factor for long-term survival in breast
      cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4
      expression in vitro.

PMID- 19580678
TI  - Analysis of expression in the Anopheles gambiae developing testes reveals rapidly
      evolving lineage-specific genes in mosquitoes.
AB  - BACKGROUND: Male mosquitoes do not feed on blood and are not involved in delivery
      of pathogens to humans. Consequently, they are seldom the subjects of research,
      which results in a very poor understanding of their biology. To gain insights
      into male developmental processes we sought to identify genes transcribed
      exclusively in the reproductive tissues of male Anopheles gambiae pupae. RESULTS:
      Using a cDNA subtraction strategy, five male-specifically or highly male-biased
      expressed genes were isolated, four of which remain unannotated in the An.
      gambiae genome. Spatial and temporal expression patterns suggest that each of
      these genes is involved in the mid-late stages of spermatogenesis. Their
      sequences are rapidly evolving; however, two genes possess clear homologs in a
      wide range of taxa and one of these probably acts in a sperm motility control
      mechanism conserved in many organisms, including humans. The other three genes
      have no match to sequences from non-mosquito taxa, thus can be regarded as
      orphans. RNA in situ hybridization demonstrated that one of the orphans is
      transcribed in spermatids, which suggests its involvement in sperm maturation.
      Two other orphans have unknown functions. Expression analysis of orthologs of all
      five genes indicated that male-biased transcription was not conserved in the
      majority of cases in Aedes and Culex. CONCLUSION: Discovery of testis-expressed
      orphan genes in mosquitoes opens new prospects for the development of innovative
      control methods. The orphan encoded proteins may represent unique targets of
      selective anti-mosquito sterilizing agents that will not affect non-target
      organisms.

PMID- 19580680
TI  - Different gait tasks distinguish immediate vs. long-term effects of concussion on
      balance control.
AB  - The purpose of this study was to longitudinally compare the sensitivity of
      previously documented paradigms for measuring balance control during gait
      following a concussion. We hypothesized that gait with a concurrent cognitive
      task would be most sensitive to the effects of concussion on dynamic balance
      control. Individuals with concussion (n = 30) and matched controls (n = 30)
      performed a single task of level walking, attention divided walking, and an
      obstacle-crossing task at two heights. Testing occurred four times post-injury.
      Balance control during gait was assessed with whole-body center of mass and
      center of pressure motion. The single-task level walking task did not result in
      any significant differences in balance control between individuals with
      concussion and control subjects. Within 48 hours post-injury, individuals with
      concussion walked slower and allowed less motion of their center of mass in the
      sagittal plane when attention was divided during walking, but there were no group
      differences by day 6 for this task. Group differences in balance control during
      obstacle crossing was unremarkable during the first two testing sessions, but by
      day 14 individuals with concussion displayed less mediolateral motion of their
      center of mass. Attention divided gait is able to better distinguish gait
      adaptations immediately following a concussion, but obstacle crossing can be used
      further along in the recovery process to detect new gait adaptations.

PMID- 19580681
TI  - An assessment of functioning and non-functioning distractors in multiple-choice
      questions: a descriptive analysis.
AB  - BACKGROUND: Four- or five-option multiple choice questions (MCQs) are the
      standard in health-science disciplines, both on certification-level examinations
      and on in-house developed tests. Previous research has shown, however, that few
      MCQs have three or four functioning distractors. The purpose of this study was to
      investigate non-functioning distractors in teacher-developed tests in one nursing
      program in an English-language university in Hong Kong. METHODS: Using item
      analysis data, we assessed the proportion of non-functioning distractors on a
      sample of seven test papers administered to undergraduate nursing students. A
      total of 514 items were reviewed, including 2056 options (1542 distractors and
      514 correct responses). Non-functioning options were defined as ones that were
      chosen by fewer than 5% of examinees and those with a positive option
      discrimination statistic. RESULTS: The proportion of items containing 0, 1, 2,
      and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively.
      Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors.
      Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n
      = 158) had a choice frequency of 0. Items with more functioning distractors were
      more difficult and more discriminating. CONCLUSION: The low frequency of items
      with three functioning distractors in the four-option items in this study
      suggests that teachers have difficulty developing plausible distractors for most
      MCQs. Test items should consist of as many options as is feasible given the item
      content and the number of plausible distractors; in most cases this would be
      three. Item analysis results can be used to identify and remove non-functioning
      distractors from MCQs that have been used in previous tests.

PMID- 19580683
TI  - Viewpoints: contrasting opinions in Neural Development.

PMID- 19580682
TI  - Retinal waves are likely to instruct the formation of eye-specific
      retinogeniculate projections.
AB  - Prior to eye-opening and the development of visual responses, the retina exhibits
      highly correlated spontaneous firing pattens termed retinal waves. Disruption of
      the normal spontaneous firing pattern either genetically or pharmacologically
      prevents the eye-specific refinement of retinogeniculate afferents. Here I
      provide the evidence that retinal waves play an instructive role in this process.
      In addition, I argue that a full understanding requires an identification of the
      features of retinal activity that drive the refinement as well as an
      understanding of mechanisms that transform these signals into axonal
      rearrangements.

PMID- 19580684
TI  - Retinal waves are unlikely to instruct the formation of eye-specific
      retinogeniculate projections.
AB  - In all mammalian species the projections of the two eyes to the dorsal lateral
      geniculate nucleus are initially overlapping before gradually forming the eye
      specific domains evident at maturity. It is widely thought that retinal waves of
      neuronal activity play an instructional role in this developmental process. Here,
      I discuss the myriad reasons why retinal waves are unlikely to have such a role,
      and suggest that eye-specific molecular cues in combination with neuronal
      activity are most probably involved in the formation of eye-specific
      retinogeniculate projections.

PMID- 19580686
TI  - Accurate localization of life threatening colonic hemorrhage during nuclear
      medicine bleeding scan as an aid to selective angiography.
AB  - PURPOSE: To describe a new technique to help localize life threatening colorectal
      bleeding during nuclear medicine bleeding scan to aid in selective angiography.
      METHODS: During the gastrointestinal bleeding scan, a simple metallic marker
      (paper clip) was used to localize the bleeding site on the patient body.
      Angiography was then performed within 2 hours. The marker was then used to guide
      superselective angiography and embolization. RESULTS: 5 cases of patients with
      colorectal bleeding were performed using this technique with cessation of
      bleeding in 4/5 initial attempts. 1 patient required a repeat angiogram that did
      demonstrate the bleeding on the second attempt allowing superselective
      angiography and embolization that resulted in cessation of bleeding. This patient
      with a rectal bleed required selection of additional vessels guided by the marker
      on the second attempt. CONCLUSION: The dilemma of positive scintigraphic evidence
      of colonic bleeding with negative arteriography can be resolved with the use of a
      metal marker during the scintigram to guide superselective angiography. Although
      in our small series of patients this technique appears to be simple and
      effective, further clinical investigation is warranted with a larger patient
      population. This technique may offer a role in therapy in coordination with the
      colorectal surgeon for the high risk patient in an otherwise life threatening
      situation.

PMID- 19580685
TI  - Evidence for oxidative stress in the developing cerebellum of the rat after
      chronic mild carbon monoxide exposure (0.0025% in air).
AB  - BACKGROUND: The present study was designed to test the hypothesis that chronic
      very mild prenatal carbon monoxide (CO) exposure (25 parts per million) subverts
      the normal development of the rat cerebellar cortex. Studies at this chronic low
      CO exposure over the earliest periods of mammalian development have not been
      performed to date. Pregnant rats were exposed chronically to CO from gestational
      day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group
      A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to
      CO from postnatal day 5 (P5) to P20; group C: postnatal exposure only, from P5 to
      P20, and group D, controls (air without CO). At P20, immunocytochemical analyses
      of oxidative stress markers, and structural and functional proteins were assessed
      in the cerebellar cortex of the four groups. Quantitative real time PCR assays
      were performed for inducible (iNOS), neuronal (nNOS), and endothelial (eNOS)
      nitric oxide synthases. RESULTS: Superoxide dismutase-1 (SOD1), SOD2, and
      hemeoxygenase-1 (HO-1) immunoreactivity increased in cells of the cerebellar
      cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased
      in blood vessels and Purkinje cells (PCs) of pups from group-A, B and C. By
      contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS
      immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for
      iNOS were significantly up-regulated in the cerebellum of rats from group B;
      however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A,
      B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry
      for neurofilaments (structural protein), synapsin-1 (functional protein), and
      glutamic acid decarboxylase (the enzyme responsible for the synthesis of the
      inhibitory neurotransmitter GABA), were decreased in groups A and B.
      Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin,
      remained unchanged. The immunoreactivity of the astrocytic marker GFAP increased
      after prenatal exposure. CONCLUSION: We conclude that exogenously supplied CO
      during the prenatal period promotes oxidative stress as indicated by the up
      regulation of SOD-1, SOD-2, HO-1, Ferritin-H, and iNOS with increased
      nitrotyrosine in the rat cerebella suggesting that deleterious and protective
      mechanisms were activated. These changes correlate with reductions of proteins
      important to cerebellar function: pre-synaptic terminals proteins (synapsin-1),
      proteins for the maintenance of neuronal size, shape and axonal quality
      (neurofilaments) and protein involved in GABAergic neurotransmission (GAD).
      Increased GFAP immunoreactivity after prenatal CO-exposure suggests a glial
      mediated response to the constant presence of CO. There were differential
      responses to prenatal vs. postnatal CO exposure: Prenatal exposure seems to be
      more damaging; a feature exemplified by the persistence of markers indicating
      oxidative stress in pups at P20, following prenatal only CO-exposure. The
      continuation of this cellular environment up to day 20 after CO exposure suggests
      the condition is chronic. Postnatal exposure without prenatal exposure shows the
      least impact, whereas prenatal followed by postnatal exposure exhibits the most
      pronounced outcome among the groups.

PMID- 19580687
TI  - A pilot study on the molecular phylogeny of Drepanoidea (Insecta: Lepidoptera)
      inferred from the nuclear gene EF-1alpha and the mitochondrial gene COI.
AB  - A molecular phylogenetic study of the Drepanoidea based on the EF-1alpha
      sequences and combined EF-1alpha and COI sequences was carried out in order to
      infer higher classification at and above the subfamily level. The sample
      contained 14 taxa representing 13 genera recognized in the Drepanoidea. The
      results revealed that the Drepaninae, Thyatirinae and Cyclidiinae respectively
      form monophyletic groups. The sister relationship between the Drepaninae and the
      Thyatirinae was validated. The monophyly of the Cyclidiinae with the
      Drepaninae+Thyatirinae was supported robustly. Hypsomadius insignis and Oreta
      vatama within the traditional definition of the Drepaninae formed an individual
      clade with robust support (100%) and constitutes a sister relationship to a clade
      containing the rest of the Drepaninae in all the topologies, which means that the
      subfamily Oretinae of the Drepanidae should be restored. The family Drepanidae is
      divided into four subfamilies: Drepaninae, Oretinae, Thyatirinae and Cyclidiinae
      in this work. The family Epicopeiidae formed a monophyly with high bootstrap
      values. The result of combined analysis of EF-1alpha and COI showed that the
      Epicopeiidae have a closer phylogenetic relationship with the Geometridae than
      with the Drepanidae and belong to neither the Drepanoidea nor the Geometroidea.

PMID- 19580688
TI  - Trichinella zimbabwensis in a naturally infected mammal.
AB  - Trichinella zimbabwensis has been detected in wild and farmed Nile crocodiles
      (Crocodylus niloticus) and in wild monitor lizards (Varanus niloticus) of several
      African countries, but it has never been detected in mammals in nature, in spite
      of its infectivity to rodents, pigs, foxes and monkeys under laboratory
      conditions. The aim of this work was to describe the first detection of T.
      zimbabwensis in a naturally infected lion (Panthera leo) of the Kruger National
      Park (KNP) of South Africa. The sequence of the expansion segment V, a highly
      variable non-coding sequence of the large subunit ribosomal RNA of the genus
      Trichinella, of larvae from the lion was identical to that of larvae of T.
      zimbabwensis collected from a Nile crocodile originating from the same locality
      as the lion, suggesting a possible transmission of this parasite between mammals
      and reptiles. The KNP proves to be a very interesting area for parasites of the
      genus Trichinella since three taxa (Trichinella nelsoni, Trichinella T8 and T.
      zimbabwensis) circulate among the wildlife of this protected area.

PMID- 19580689
TI  - The helminth community of the wood mouse Apodemus sylvaticus in a Mediterranean
      ecosystem in regeneration ten years after a wildfire.
AB  - This study was carried out 10 years after a wildfire in the Spanish Serra
      Calderona Natural Park, following a previous analysis comprising the first 5
      years after the fire. Its primary aim was to elucidate the impact of this
      perturbation on the population biology of the wood mouse Apodemus sylvaticus, and
      the repercussions on its helminth community in this regenerating Mediterranean
      ecosystem. Second, confirmation of the ability of the parasites to tolerate
      environmental stressors and the effects on their transmission strategies was
      sought. Five hundred and sixty-four individuals of A. sylvaticus were studied in
      a 9-year period, from the second to the tenth post-fire year: 408 mice from the
      burned area and 156 from the control--non-burned--area. The helminth community
      for both areas and the effect of intrinsic (host age and sex) and extrinsic
      (site, period and year of capture) factors on helminth prevalence, abundance and
      diversity, and species richness were analysed. Our findings show that, after an
      environmental disaster, the behaviour of helminth species might be related to
      their pre-catastrophe presence, their biological cycles, the host's immunological
      condition, the change of host dynamics, the direct effects of the perturbation,
      and the processes related to the re-establishment of the ecological balance of a
      devastated ecosystem.

PMID- 19580690
TI  - Philometra floridensis sp. n. (Nematoda: Philometridae) from the ovary of red
      drum Sciaenops ocellatus (Osteichthyes: Sciaenidae) off the coast of Florida,
      USA.
AB  - A new nematode species, Philometra floridensis sp. n. (Philometridae), is
      described from male and female specimens found in the ovary of red drum,
      Sciaenops ocellatus (Linnaeus) (Sciaenidae, Perciformes), from the Gulf of Mexico
      off Treasure Island, Florida, USA. Based on light and scanning electron
      microscopy examination, the new species differs from most other gonad-infecting
      Philometra spp. in having a smooth gubernaculum with a distinct dorsal tooth on
      the distal tip. The new species is most similar to P. carolinensis Moravec, de
      Buron & Roumillat, 2006, but differs in length and shape of spicules. It can be
      distinguished from P. carolinensis and other species with unknown males, by the
      markedly greater body length of gravid females (up to about 100 cm). Philometra
      floridensis is the third valid gonad-infecting species of Philometra reported
      from sciaenids.

PMID- 19580691
TI  - Parotid lymphoma in west Scotland: two-year 'snapshot' of diagnosis, management
      and core issues.
AB  - OBJECTIVES: To establish whether there is a requirement for a network policy on
      management of suspected intraparotid lymphoma, and to answer the question, 'Can
      lymphoma of the parotid region be adequately diagnosed, typed and treated on the
      basis of a core biopsy, within the West of Scotland?' METHOD: We identified 22
      patients from the West of Scotland Managed Clinical Network database who had been
      diagnosed between 2003 and 2005 with lymphoma of the parotid region (nodal or
      extranodal). These 22 cases were reviewed, assessing specifically their
      investigation and diagnosis (compared with the World Health Organization
      classification of parotid lymphoma). RESULTS: Three of the 22 patients underwent
      core biopsy to diagnose and type their lymphoma. All these procedures were
      performed within a single centre. CONCLUSION: It is possible to successfully
      perform core biopsy of parotid lymphoma lesions (generally under ultrasonic
      guidance). This may obviate the need for open procedures. Close collaboration
      with haematology, pathology, radiology, and head and neck colleagues is required.

PMID- 19580692
TI  - Digenean diversity in labrid fish from the Bay of Bizerte in Tunisia.
AB  - Six species of digeneans (Proctoeces maculatus (Looss, 1901), Helicometra
      fasciata (Odhner, 1902), Helicometra pulchella (Odhner, 1902), Macvicaria alacris
      (Looss, 1901), Peracreadium genu (Nicoll, 1909) and Zoogonus rubellus (Olson,
      1868)) were found for the first time in labrid fish (Symphodus tinca (Linnaeus,
      1758), Labrus merula (Linnaeus, 1758) and Labrus viridis (Linnaeus, 1758)) from
      the Bay of Bizerte. Except for P. maculatus and Z. rubellus, which are limited to
      the rectum, these helminths colonize the entire digestive tract. The study of the
      seasonal prevalence, abundance and mean intensity shows that three parasites, P.
      maculatus, H. fasciata and P. genu are present throughout the year while H.
      pulchella, M. alacris and Z. rubellus are less frequent and appear only in spring
      (H. pulchella and M. alacris) or in spring and summer (Z. rubellus). The levels
      of infection and digenean faunal diversity in labrid fish from the Tunisian
      coasts are generally lower than those from localities within the western
      Mediterranean.

PMID- 19580693
TI  - Initial high rate of misdiagnosis in Crimean Congo haemorrhagic fever patients in
      an endemic region of Turkey.
AB  - Crimean Congo haemorrhagic fever (CCHF) has been an emerging tick-borne infection
      in some parts of Turkey since 2002, with a number of fatalities. Many of the
      initial non-specific symptoms of CCHF can mimic other common infections.
      Additionally, the seasonal pattern of the epidemic, and the waning attention of
      healthcare workers to the yearly index cases caused some delays in appropriate
      patient care and treatment. Between March 2004 and August 2008, 140 confirmed
      adult cases were evaluated retrospectively for initial diagnosis and treatment
      delays. This study clearly demonstrated that there are particular delays (4.8
      days) in the referral system to initiate effective antiviral treatment in the
      tertiary-care centre which significantly affect fatality rates (P>0.05). A large
      number of patients (n=95, 68%) received an initial misdiagnosis of various
      infections other than CCHF. In conclusion, continuous medical education regarding
      CCHF in the epidemic area is essential in order to achieve a better survival rate
      from this deadly infection.

PMID- 19580694
TI  - Evaluation of pertussis immunity status in schoolchildren immunized with whole
      cell vaccine.
AB  - It has recently been reported that the worldwide increase in the number of
      pertussis cases is a result of the waning of whole-cell vaccine-induced immunity.
      Thus, in this study, we aimed to investigate the pertussis immunity status of
      primary and secondary school students in a district of Ankara, Turkey. A total of
      997 healthy students, aged 9-17 years, who had been immunized with four doses of
      whole-cell pertussis vaccine were included in the study. The subjects were
      divided into two age groups: 9-14 and 15-17 years. To determine the immune
      status, serum levels of IgG anti-pertussis toxin (aPT) antibody were tested by in
      house ELISA and arbitrarily evaluated as non-immune [< 10 ELISA units (EU)/ml],
      immune (10-100 EU/ml), and recent infection (> 100 EU/ml). Serum samples of 997
      students (559 females, 438 males) aged between 9 and 17 years (mean 13.02 +/-
      2.25, median 13 years) were tested. Non-immune, immune and recent infection
      levels of aPT were found in 27.3%, 59.3% and 13.4% of individuals, respectively.
      The immune group did not have statistically significant differences between males
      and females (P = 0.68). In the 9-14 and 15-17 years age groups, serum aPT
      antibody levels 10 EU/ml were 73.1% and 72.2%, respectively, which did not
      represent any statistical difference (P = 0.81). Students aged 15-17 years had a
      higher immunity rate than the 9-14 years group, and the percentage of students
      with recent infection in the 9-14 years group was higher than the 15-17 years
      group (P < 0.001). The peak age of non-immunized subjects was 9 years (47.0%),
      and decreased to a minimum at age 12-13 years, and began to increase again from
      age 13-14 years. In contrast, the ratio of recent infection was least at age 9-10
      years, began to increase, and reached a peak at 12 years, and then decreased. On
      the other hand, it was observed that household size and monthly income were not
      associated with the immunity status (P = 0.65, P = 0.37, respectively). The
      results of the present study show that levels of antibody against pertussis
      decreased in the younger age groups and, as a result, there is an increase in the
      number of pertussis cases. Thus, in order to decrease the incidence of pertussis
      and protect infants, we recommend the application of booster doses at regular
      intervals.

PMID- 19580696
TI  - Impact of mindfulness on cognition and affect in voice hearing: evidence from two
      case studies.
AB  - BACKGROUND: There is a small body of research indicating that mindfulness
      training can be beneficial for people with distressing psychosis. What is not yet
      clear is whether mindfulness effects change in affect and cognition associated
      with voices specifically. This study examined the hypothesis that mindfulness
      training alone would lead to change in distress and cognition (belief conviction)
      in people with distressing voices. METHOD: Two case studies are presented.
      Participants experienced long-standing distressing voices. Belief conviction and
      distress were measured twice weekly through baseline and mindfulness
      intervention. Mindfulness in relation to voices was measured at the start of
      baseline and end of intervention. RESULTS: Following a relatively stable baseline
      phase, after 2-3 weeks of mindfulness practice, belief conviction and distress
      fell for both participants. Both participants' mindfulness scores were higher
      post treatment. CONCLUSION: Findings show that mindfulness training has an impact
      on cognition and affect specifically associated with voices, and thereby
      beneficially alters relationship with voices.

PMID- 19580695
TI  - Assessing the impact of climate change on vector-borne viruses in the EU through
      the elicitation of expert opinion.
AB  - Expert opinion was elicited to undertake a qualitative risk assessment to
      estimate the current and future risks to the European Union (EU) from five vector
      borne viruses listed by the World Organization for Animal Health. It was
      predicted that climate change will increase the risk of incursions of African
      horse sickness virus (AHSV), Crimean-Congo haemorrhagic fever virus (CCHFV) and
      Rift Valley fever virus (RVFV) into the EU from other parts of the world, with
      African swine fever virus (ASFV) and West Nile virus (WNV) being less affected.
      Currently the predicted risks of incursion were lowest for RVFV and highest for
      ASFV. Risks of incursion were considered for six routes of entry (namely vectors,
      livestock, meat products, wildlife, pets and people). Climate change was
      predicted to increase the risk of incursion from entry of vectors for all five
      viruses to some degree, the strongest effects being predicted for AHSV, CCHFV and
      WNV. This work will facilitate identification of appropriate risk management
      options in relation to adaptations to climate change.

PMID- 19580697
TI  - Pharmacotherapy of adult attention deficit hyperactivity disorder (ADHD): a meta
      analysis.
AB  - Our objective was to conduct a meta-analysis of therapeutic efficacy of
      pharmacological treatment of adult ADHD based on data from controlled clinical
      trials. We used the search engines PubMed and Medline to identify relevant
      clinical trials. Short-term studies with double-blind parallel-group design were
      selected for the analysis. Altogether, we identified 11 trials that met the
      criteria, and investigated a total of 1991 subjects, 694 and 1297 of whom were
      treated with placebo or active medication, respectively. In order to pool
      efficacy data from studies with different characteristics, including different
      number of participants, different trial duration and measures of efficacy, the
      statistical effect sizes for each study had to be calculated. Our findings showed
      that the pooled effect size across all treatments was in the medium-to-high range
      (Cohen's d=0.65, p<0.0001 vs. placebo), and the effect size for stimulants
      (Cohen's d=0.67, p<0.0001 vs. placebo) was somewhat higher than for non-stimulant
      medications (Cohen's d=0.59, p<0.0001 vs. placebo). The current database of
      controlled trials for adult ADHD is relatively small, and does not include data
      for many of the potentially important agents. In addition, effect-size estimates
      for different classes of medications (i.e. stimulant and non-stimulant
      medications) were based on separate studies; head-to-head comparisons of various
      agents are severely lacking. Nonetheless, results of this meta-analysis across
      all ADHD medications in adult subjects demonstrated statistically significant and
      clinically robust improvement in symptom severity compared to placebo treatment.

PMID- 19580698
TI  - Increase of SCF plasma concentration during donepezil treatment of patients with
      early Alzheimer's disease.
AB  - Alzheimer's disease (AD) can be treated with inhibitors of the enzyme
      acetylcholinesterase (AChE). There is evidence that AChE inhibitors promote
      neuroprotective effects and neurogenesis in the central nervous system (CNS).
      However, the mechanisms by which AChE inhibitors mediate these effects are still
      not well understood. One possible mechanism could be the up-regulation of
      haematopoietic growth factors (HGFs), also known to promote neuroprotective
      effects and to stimulate neurogenesis in the CNS. In the present study we
      investigated the impact of a 15-month treatment with the AChE inhibitor donepezil
      on blood levels of the HGFs stem cell factor (SCF), stromal cell-derived factor 1
      (SDF-1), granulocyte colony- stimulating factor (G-CSF) and vascular endothelial
      growth factor (VEGF) in 19 patients with AD and 45 age-matched healthy controls.
      Before treatment with donepezil we found in AD patients significantly decreased
      SCF plasma concentrations (661.1+/-40.0 pg/ml) compared to healthy controls
      (997.7+/-33.7 pg/ml, p<0.001) but no significant differences between both groups
      concerning blood levels of SDF-1, G-CSF and VEGF. After 15 months' treatment SCF
      plasma levels increased significantly in the AD patients (764.5+/-41.5 pg/ml,
      p=0.016). In addition, we found a significant positive correlation between SCF
      plasma levels at baseline and changes of cognitive functions over the 15-month
      period (r=0.521, p=0.022). For the other HGFs we were unable to show a
      significant impact of donepezil treatment. Our findings indicate that donepezil
      treatment of AD patients is associated with an up-regulation of SCF plasma
      levels, which may contribute to neuroprotection and neurogenesis in the CNS.

PMID- 19580699
TI  - Bread type intake is associated with lifestyle and diet quality transition among
      Bedouin Arab adults.
AB  - The traditionally semi-nomadic Bedouin Arabs in Israel are undergoing
      urbanisation with concurrent lifestyle changes, including a shift to using
      unfortified white-flour bread instead of wholewheat bread as the main dietary
      staple. We explored associations between the transition from wholewheat to white
      flour bread and (1) lifestyle factors, (2) overall diet quality, and (3) health
      status. We conducted a nutrition survey among 451 Bedouin adults, using a
      modified 24 h recall questionnaire. Bread intake accounted for 32.7 % of the
      total energy intake. Those consuming predominantly white bread (PWB) (n 327) were
      more likely to be urban (OR 2.79; 95 % CI 1.70, 4.58), eating store-bought rather
      than homemade bread (OR 8.18; 95 % CI 4.34, 15.41) and currently dieting (OR
      4.67; 95 % CI 1.28, 17.11) than those consuming predominantly wholewheat bread
      (PWWB) (n 124). PWB consumption was associated with a lower intake of dietary
      fibre (23.3 (se 0.6) v. 41.8 (se 1.0) g/d; P < or = 0.001), a higher intake of
      saturated fats (26.9 v. 24.6 % of total fat; P = 0.013) and lower intakes of Fe
      (11.0 (se 0.3) v. 16.7 (se 0.4) mg/d), Mg (262.2 (se 5.9) v. 490.3 (se 9.8)
      mg/d), vitamin E (6.5 (se 0.2) v. 8.6 (se 0.3) mg/d) and most B vitamins than
      PWWB consumption (P < 0.001 for all), after adjusting for total energy intake.
      Among those aged > or = 40 years, PWB consumption was associated with a 9.85-fold
      risk (95 % CI 2.64, 36.71; P = 0.001) of having one or more chronic conditions,
      as compared with PWWB consumption, after controlling for other risk factors.
      White bread intake was associated with a less traditional lifestyle and poorer
      diet quality, and may constitute a useful marker for at-risk subgroups to target
      for nutritional interventions.

PMID- 19580700
TI  - Image descriptions in early and mid-level vision: what kind of model is this and
      what kind of models do we really need?
AB  - In The utility of image descriptions in the initial stages of vision: A case
      study of printed text, Watt and Dakin (2010) describe a model that integrates
      mechanisms at both early and middle stages of visual processing, and provide a
      demonstration of the application of the model to the relational organization of
      printed text. In the following, we discuss a number of the merits of this
      approach, but argue that it is (at this stage) highly difficult to assess the
      utility of this model as a plausible description of human visual processing.
      First, we indicate that the authors' description of the model is underspecified.
      Second, we question the generalizability of the model. Third, we argue that the
      model needs to be directly compared to quantitative empirical data. Fourth, we
      argue that the model needs to be directly compared to alternative models.

PMID- 19580701
TI  - Recalling pain experienced during a colonoscopy: pain expectation and
      variability.
AB  - OBJECTIVES: This study investigated the relationship between participants'
      expected levels of pain intensity before a colonoscopy, pain intensity
      experienced while they were undergoing this medical procedure (real-time pain),
      and their retrospective evaluation of this experience. DESIGN: Correlational
      design. Regression analyses were performed and mediational models were tested.
      METHODS: Ninety patients who were about to undergo a colonoscopy were asked to
      report the pain intensity on a scale ranging from 0 (no pain) to 10 (extreme
      pain). They reported the expected intensity of pain before the examination, their
      real-time intensity of pain every 60 s during the colonoscopy, and their global
      retrospective evaluation of the pain experienced when the procedure was over.
      RESULTS: Results confirmed that, regardless of participants' gender, the
      variability of the real-time pain distribution was a significant predictor of the
      accuracy of recall (i.e. the discrepancy between recalled pain and mean real-time
      pain). Moreover, participants' pain expectations preceding the examination were a
      significant predictor of the accuracy of recall. It was further demonstrated that
      the effect of patients' expectations on the discrepancy was mediated by the real
      time pain variability. CONCLUSIONS: The results of the present study provide
      useful indications about what the target of interventions aimed at reducing the
      bias in pain recall should be.

PMID- 19580702
TI  - The effects of telephone prompting on attendance for starting treatment and
      retention in treatment at a specialist alcohol clinic.
AB  - OBJECTIVE: To examine the effects of telephone prompting on attendance for the
      start of treatment and retention in treatment in a specialist alcohol clinic.
      METHOD: The study setting was a specialist alcohol treatment clinic. Participants
      were 172 clients attending as out-patients. An ABABAB design was used with
      planned alternating conditions, respectively, with or without a telephone prompt
      the day before the client was due to attend, over a succession of six consecutive
      4-week periods. RESULTS: Clients who were prompted were more likely to start
      treatment and attend further treatment sessions than clients who were not
      prompted. CONCLUSIONS: Telephone prompting is a simple and effective way to
      improve attendance for the start of treatment and retention in alcohol treatment.

PMID- 19580703
TI  - Illness perceptions in anorexia nervosa: a qualitative investigation.
AB  - OBJECTIVES: Anorexia nervosa (AN) is an eating disorder characterized by the
      egosyntonic nature of symptoms, denial of illness, and ambivalence about
      treatment engagement. Within the physical health literature, people's beliefs
      about their illness have been found to impact upon coping and treatment outcomes
      and this has largely been explored using the self-regulation model. This model
      has also been applied to mental health and more recently to AN, with beliefs
      about the disorder being associated with readiness to change. However,
      qualitative investigations have indicated that physical health models have
      limited applicability for assessing people's beliefs about mental illness. This
      may be particularly pertinent to AN, given the complexity of the disorder.
      Therefore, this study explored illness perceptions in AN using a qualitative
      design which was not restricted by a physical illness model but focused on
      personal models of AN from the perspective of those experiencing the disorder.
      DESIGN: Semi-structured interviews were conducted with thirteen participants who
      were currently in treatment for AN. METHOD: Interview transcripts were analysed
      using grounded theory methodology. RESULTS: An interpretative theory of illness
      perceptions in AN was developed and comprised four related categories: 'making
      sense of AN', 'the relationship between AN and the self', 'the recovery
      struggle', and 'coping with treatment'. CONCLUSION: Patient's accounts
      transcended the dimensions offered by physical illness models, with the
      implication that methods for assessing illness beliefs in AN require adaptation
      for a full understanding to be gained and the complexity of perceptions to be
      captured.

PMID- 19580704
TI  - Autobiographical memory specificity, depression, and trauma in bipolar disorder.
AB  - OBJECTIVES: In a bipolar disorder (BD) sample, the present study investigated:
      (i) the prevalence of trauma; (ii) the specificity of autobiographical memory
      (AM); (iii) the influence of childhood trauma on AM specificity, current inter
      episode depressive mood, and BD severity; (iv) if AM specificity moderates the
      influence of childhood trauma on current inter-episode depressive mood and BD
      severity. METHODS: Fifty-two participants were recruited from a geographically
      well-defined mental health service in Northern Ireland. The AM test, self-report
      measures of lifetime experience of trauma, childhood trauma, and depression were
      administered. Severity of BD was estimated utilizing a systematic tool for
      reviewing all available clinical data of participants. RESULTS: A high prevalence
      of trauma was found. A total of 94.2% (49/52) of participants reported
      experiencing a traumatic event in either childhood or adulthood. AM specificity
      was significantly lower than previous reports of such in major depression.
      However, whilst childhood trauma predicted current inter-episode depressive mood,
      childhood trauma was not predictive of BD severity or AM specificity. Moreover,
      the association between childhood trauma and depressed mood was not moderated by
      AM specificity. CONCLUSIONS: The findings of this study suggest a relationship
      between early psychosocial adversity and current inter-episode depressive mood in
      BD. In addition, levels of overgeneral AM are similar to that reported for
      depression, but are unrelated to childhood trauma, current inter-episode
      depressive mood, or BD severity. Clinical implications include the importance of
      routine assessment of trauma in BD and the need for adjunctive evidenced-based
      psychological therapies.

PMID- 19580705
TI  - [Necrotizing soft tissue infections in intravenous drug users].

PMID- 19580706
TI  - Randomized study on the effects of different strategies of intermittent pneumatic
      compression for lower limb claudication.
AB  - BACKGROUND: The aim of the present study was to evaluate the efficacy of
      different strategies of intermittent pneumatic compression (IPC) for the
      treatment of lower limb claudication. METHODS: Five study groups were
      prospectively studied. Group 1: 9 patients not undergoing IPC; Group 2; six
      patients undergoing IPC 1 hour/thrice-a-day/4 months; Group 3: six patients
      undergoing IPC 2 hours/once-a-day/4 months; Group 4; six patients undergoing IPC
      1 hour/thrice-a-day/2 months; Group 5: six patients undergoing IPC 2 hours/once-a
      day/2 months. RESULTS: All patients completed the planned treatment schedule and
      stated a compliance of 33% in group 2, 83% in group 3, 66% in group 4 and 100% in
      group 5. Peak systolic velocity of the popliteal artery blood flow increased over
      baseline values particularly when IPC lasted 4 months (group 2: 85%, group 3: 81%
      vs. group 4: 76%, group 5: 73%). These beneficial effects lasted 10 months and
      vanished 14 months after the end of IPC treatment. The absolute claudication
      distance increased at the end of the treatment of 101% in group 2, 94% in group
      3, 86% in group 4, and 83% in group 5, and it was still increased over the
      baseline values 14 months after the end of the treatment. No differences have
      been observed whether the treatment was performed once- or thrice-a-day.
      CONCLUSIONS: ICP treatment performed two hours once-a-day for four months provide
      excellent results with satisfactory treatment compliance. However, these effects
      are not durable and vanish about one year after the end of IPC treatment.

PMID- 19580707
TI  - [An unusual localization of thryoglossal duct cyst].
AB  - Thyroglossal duct cysts are most common neck masses after benign lymphonodes.
      They originate from primitive thiroglossal duct, so they could be locate along
      its course. Every mass in the middle line of the neck can be considered as a
      thyroglossal cyst. Best treatment is surgery (Sistrunk procedure). We present a
      case of unusual localization at floor of the mouth of thyroglossal in a 34 years
      old woman. To our knowledge in literature, only two cases, have been reported
      both.

PMID- 19580708
TI  - [Gastrointestinal stromal tumors (GISTs). Personal experience on three cases of
      the tumors of the small intestine complicated and emergency surgically treated].
AB  - INTRODUCTION: GISTs, a new nosological entity recently described, represent a
      peculiar model of solid tumor: the identification of the molecular mechanism
      responsible for the oncogenesis led to the development of a new drug (imatinib)
      active on the specific molecular target, represented by the product of the
      mutated proto-oncogene c-kit which is a tyrosine kinase receptor that becomes
      constitutively active by mutation. Surgical resection, nevertheless, is still the
      primary treatment and it has to be as complete as possible. These two treatments
      can be integrated. GISTs are not uniformly kit-positive, and they can be
      alternatively due to mutations of the PDGFRA gene or, in patients with
      neurofibromatosis type 1 (NF-1), to generally isolated mutations of the NF-1
      gene. PATIENTS AND METHODS: We describe 3 cases of kit-positive GISTs of the
      small intestine (SISTs), complicated and emergency surgically treated: case 1--53
      years, female, with small bowel obstruction and concomitant acute intestinal
      bleeding; case 2--71 years, male, with NF-1 and acute intestinal bleeding; case 3
      -47 years, male, with perforation of the Treitz tract. The first two cases have
      been treated with intestinal resection and immediate mechanical anastomosis; the
      third one with resection of the pedunculated tumor at its base, where is situated
      the perforation too. CONCLUSIONS: SISTs (20-30%), with little or no symptoms in
      the initial phases, show notable diagnostic difficulties. Their aspecific and
      late clinical presentation--typical of this site and of the pathology that we are
      talking about--and the difficult physical-instrumental approach to small bowel
      limit the possibility of an accurate diagnosis and expose the patient to
      potentially fatal acute complications and to risks related to emergency surgery
      treatment that decreases the possibility of a radical resection.

PMID- 19580709
TI  - [Intestinal schwannoma: case report and literature review].
AB  - Digestive Tract Schwannomas (DTS) are benign mesenchymal tumours, usually
      affecting female between 20 and 70 years old. They are most commonly found in the
      stomach but they can arise anywhere from the digestive tract. DTS are usually
      asymptomatic but can present with different symptoms. Definitive diagnosis can
      only be made with immunohistochemistry because endoscopy and computed tomography
      can't distinguish them from other non epithelial neoplasms. Surgical resection is
      the treatment of choice.

PMID- 19580710
TI  - [Splenic congenital cysts as incidental finding during emergency sonography:
      differential diagnostic and therapeutic indications. Case report].
AB  - Splenic cysts are occasionally discovered during instrumental investigations
      performed for other reasons. Clinical exam is in fact negative in presence of the
      non complicated small lesions, such those ones identified with sonography in a
      young man, controlled in our Emergency Unit for car crash. Anamnestic report and
      clinical evaluation have supported congenital etiology of focal lesions, observed
      in kidneys too, confirming the polydistrectuality of the abnormality, which must
      be only periodically controlled, if it's not complicated.

PMID- 19580711
TI  - [Diaphragmatic rupture with intrathoracic hepatic dislocation. Two case report].
AB  - The authors show two cases of diaphragmatic rupture by blunt trauma with intra
      thoracic liver dislocation due to an accident on the street. The preoperative
      diagnosis has been based on the CT scan. The laparotomy, central for a patient
      and sub costal bilateral for the other one, gave the chance to repair the
      diaphragmatic defect directly and to deal with the associated lesions existing in
      both the casualties. No prosthetic material has been used and the reconstruction
      of the diaphragmatic defect has been conducted through a interrupted suture with
      non absorbable material. According to our experience the reparation of the
      diaphragmatic defect has always been conducted through a laparotomic approach and
      without using any prosthetic material. We repute that in these cases the
      laparotomic approach is the best one, which permits not only the reparation of
      the diaphragmatic defect but also the correct management of the related lesions
      which could be present. Usually we use a interrupted suture with non absorbable
      material for minor lesions and a continuous one, double layered if possible, for
      the major ones.

PMID- 19580712
TI  - [An evidence-based approach to the laparoscopic repair of paraesophageal
      hernias].
AB  - The approach to paraesophageal hernias has drastically changed over the last
      decade. The goal of this paper is to describe in detail our surgical technique of
      laparoscopic repair of paraesophageal hernias and to provide an evidence-based
      approach to the most controversial aspects of this type of repair.

PMID- 19580713
TI  - New trends on fibrin glue in seroma after axillary lymphadenectomy for breast
      cancer.
AB  - BACKGROUND: Axillary lymphadenectomy remains an integral part of breast cancer
      treatment, yet seroma formation occurs in 15-85% of cases. Among methods to
      reduce seroma magnitude and duration, fibrin glue has been proposed in several
      studies with controversial results. PATIENTS AND METHODS: Ninety patients
      underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy;
      a suction drain was fitted in all patients. Fibrin glue spray were applied to the
      axillary fossa in 45 patients; the other 45 patients were treated conventionally.
      RESULTS: Suction drainage was removed between post-operative (p.o.) days 3 and 4.
      Seroma magnitude and duration were significantly reduced (p 0.004 and 0.02,
      respectively), and there were fewer evacuative punctures, in patients receiving
      fibrin glue compared with the conventional treatment group. CONCLUSIONS: Use of
      fibrin glue does not always prevent seroma formation, but does reduce seroma
      magnitude, duration and evacuative punctures.

PMID- 19580714
TI  - [Overnight surgery in proctology and anesthesia type: our experience on 320
      patients].
AB  - BACKGROUND: Several evidences demonstrated that general anaesthetics associated
      with local anaesthesia show more advantages in comparison to spinal anaesthesia
      in proctological surgery. Aim of this study was to verify the efficacy of deep
      general anaesthesia associated with a loco-regional anesthesiological technique,
      in a grade population of 320 patients affected by haemorrhoidal disease and anal
      fissure. PATIENTS AND METHODS: Patients with III-IV grade haemorrhoids and
      chronic posterior anal fissures has been eligible for this study while were
      excluded patients with history of allergic reaction or pharmacological
      hypersensibility to naropine, propofol o similar drugs. All patients (group A)
      were submitted to general anaesthesia associated with loco-regional anaesthesia,
      Control patients (group B) underwent spinal anaesthesia. At the end of all
      surgery procedure, it has been evaluated the presence of early and late
      complications according to our classification recently proposed. RESULTS: A total
      of 320 patients were included, 240 submitted to haemorrhoidectomy for prolapse
      and 80 surgically treated for anal fissures. Anesthesia obtained has been
      satisfactory in the all treated patients and has not been observed permanent side
      effects. Among the early post-operative complications it has been observed
      urinary retention in 9% of patients and pain in 30%. Among late post-operative
      complications it has been observed pain in 8% and urinary retention in 1% of
      patients. In two patients has been observed the development of abscess in
      correspondence of anaesthetic infiltration area. The local anaesthetical effect
      was present for a mean period of 4-8 hours. CONCLUSIONS: Loco-regional
      anesthesiological technique with posterior block, associated to general
      anaesthesia, has been demonstrated efficacious for the treatment of the most
      frequent proctological pathologies. This method allowed a low incidence of early
      and late complications and a more fast resolution of clinical sequelae of the
      surgery.

PMID- 19580715
TI  - Acute abdomen in the elderly. A peripheral general hospital experience.
AB  - We reviewed our experience on 291 consecutive patients aged over 65 years who
      were operated on for acute abdomen during the period 2003-2007 at "Santo Spirito"
      Hospital of Casale Monferrato, a peripheral hospital in the Piedmont region. The
      mean age of the patients was 78 years and the male/female ratio was 149/142. A
      total of 126 patients (43%) had one or more associated disease. The most common
      causes for an emergency operation were mechanical bowel obstruction (45%), hollow
      viscus perforation (18%) and strangulated hernia (18%). 234 patients (80%)
      recovered and were free from major complications. The remaining 57 (20%)
      developed at least one major complication (including death). The 30-days
      postoperative deaths were 33 (11%). Nonlethal major complications were 24 (8%).
      The commonest complications were cardio-respiratory. Septic complications were
      15. Total reoperations for surgical complications were 5. Mesenteric ischaemia
      and secondary peritonitis were the most important causes of fatal outcome
      (respectively 42 and 17% of mortality). We also reported high mortality among
      patients with peritoneal carcinomatosis (24%). Emergency surgery was relatively
      safe for the remaining groups of patients, with a complexive mortality ratio of
      5.3%. We conclude that "acute abdomen" is still an appreciably frequent cause of
      death in the older age group. A high level of vigilance and early attention is
      therefore advocated. Anyway, excluding some severe conditions, the overall
      success of surgical interventions for abdominal emergency is satisfactory in the
      majority of older people. About the debated role of peripheral hospitals in the
      health care system, we conclude that the surgical treatment of the acute abdomen
      in the elderly is safe and feasible in the peripheral hospitals, and that these
      hospitals play a determining role in the management of old patients, especially
      in emergency.

PMID- 19580717
TI  - Opposing wall mechanics are significantly influenced by longitudinal cardiac
      rotation in the assessment of ventricular dyssynchrony.
AB  - OBJECTIVES: This study sought to assess whether longitudinal rotation (LR)
      affects myocardial systolic velocity profiles and to compare velocity-based
      measures of dyssynchrony with LR for predicting cardiac resynchronization therapy
      (CRT) response. BACKGROUND: Longitudinal rotation, a rocking motion often seen
      when the dilated left ventricle (LV) is imaged in its horizontal long-axis plane,
      is a recently recognized phenomenon and a new predictor of response to CRT.
      METHODS: One hundred patients with CRT implants and suitable baseline
      echocardiograms were identified. Longitudinal rotation was assessed in the apical
      4-chamber view by speckle-tracking techniques and myocardial systolic velocities
      for basal septum, and lateral LV were analyzed from tissue Doppler images. The
      quartiles of LR distribution were analyzed for differences in their systolic
      velocities. Correlation between measurements and reduction in LV end-systolic
      volume (ESV) at follow-up was performed. RESULTS: Quartile 1 had a mean LR of 
      6.8 +/- 2.3 degrees ; quartile 4 showed a mean LR of 2.3 +/- 1.6 degrees . A
      depressed peak velocity of lateral wall, when compared with the septum, was found
      for quartile 1 (p = 0.01), whereas the converse was noted in quartile 4 (p =
      0.0001). The difference in amplitude of peak velocity between septal and lateral
      walls was found to correlate with the pattern of LR and with percentage reduction
      in LV ESV at follow-up in nonischemic patients. Septal-lateral delay was not
      correlated with the presence of LR, nor was it predictive of reduction in LV ESV.
      CONCLUSIONS: Patients with prominent clockwise LR have depressed long-axis
      systolic velocities of the lateral wall, whereas the patients with
      counterclockwise LR have depressed septal wall velocities. The difference in peak
      amplitude of basal septal and lateral systolic velocities is predictive of LR,
      and in the nonischemic subgroup correlates with quantitative LV reverse
      remodeling at follow-up. Velocity time-based measures, including septal-lateral
      delay were not predictive of CRT response.

PMID- 19580718
TI  - Rock 'n roll ventricle of the dyssynchronous heart: clinical significance of
      rocking motion in selection of patient for cardiac resynchronization therapy.

PMID- 19580719
TI  - Low-flow aortic stenosis in asymptomatic patients: valvular-arterial impedance
      and systolic function from the SEAS Substudy.
AB  - OBJECTIVES: This study sought to assess the impact of valvuloarterial impedance
      on left ventricular (LV) myocardial systolic function in asymptomatic aortic
      valve stenosis (AS). BACKGROUND: In atherosclerotic AS, LV global load consists
      of combined valvular and arterial resistance to LV ejection. Global load
      significantly impacts LV ejection fraction (EF) in symptomatic AS, but less is
      known about its effect on LV myocardial function in asymptomatic AS. METHODS:
      Echocardiograms in 1,591 patients with asymptomatic AS (67 +/- 10 years, 51%
      hypertensive) at baseline in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis)
      study evaluating placebo-controlled combined simvastatin and ezetimibe treatment
      in AS were used to assess LV global load as valvuloarterial impedance and LV
      myocardial function as stress-corrected midwall shortening. The study population
      was divided into tertiles of global load. Stress-corrected midwall shortening was
      considered low if <87% in men and <90% in women. Low-flow AS was defined as
      stroke volume index <22 ml/m(2.04). RESULTS: Energy loss index decreased (0.85
      cm(2)/m(2) vs. 0.77 and 0.75 cm(2)/m(2)) and the prevalence of low stress
      corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV
      global load (all p < 0.001). The EF was low in only 2% of patients. Patients with
      low-flow AS had higher LV global load and more often low midwall shortening than
      those with normal-flow AS (9.66 +/- 2.23 mm Hg/ml.m(2.04) and 77%, vs. 6.38 +/-
      2.04 mm Hg/ml.m(2.04) and 30%, respectively, p < 0.001). In logistic regression
      analysis, LV global load was a main predictor of low stress-corrected midwall
      shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p
      < 0.001), concomitant hypertension, and aortic regurgitation. CONCLUSIONS: LV
      global load impacts LV myocardial function in asymptomatic AS independent of
      other main covariates of LV systolic function. LV myocardial systolic dysfunction
      is common in asymptomatic AS in particular in patients with low-flow AS and
      increased valvuloarterial afterload, whereas EF is generally preserved. (An
      Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis
      [Narrowing of the Major Blood Vessel of the Heart]; NCT00092677).

PMID- 19580720
TI  - Aortic stenosis: look globally, think globally.

PMID- 19580721
TI  - Prognostic value of coronary computed tomographic angiography for prediction of
      cardiac events in patients with suspected coronary artery disease.
AB  - OBJECTIVES: We assessed the rate of cardiac events after detection or exclusion
      of obstructive coronary artery disease (CAD) by coronary computed tomography
      angiography (CCTA). BACKGROUND: Several studies have demonstrated a high
      diagnostic accuracy of CCTA for detection of obstructive CAD compared with
      invasive angiography, but data regarding the clinical prognostic value of CCTA
      are limited. METHODS: In all, 1,256 consecutive patients with suspected CAD
      undergoing 64-slice CCTA in our institution between October 2004 and September
      2006 were observed prospectively for the occurrence of severe cardiac events
      (cardiac death, myocardial infarction, or unstable angina requiring
      hospitalization: primary study end point) and all cardiac events (additionally
      including revascularization >90 days after CCTA). The observed rate of all
      cardiac events was compared with the event rate predicted by the Framingham risk
      score. Obstructive CAD was defined as > or = 50% diameter stenosis in any
      coronary artery. RESULTS: During a median follow-up of 18 months (interquartile
      range 14 to 25 months), the overall rates of severe and all cardiac events were
      0.6% and 1.8%, respectively. In 802 patients without obstructive CAD, there were
      4 cardiac events, of which 1 was severe, whereas in 348 patients with obstructive
      CAD, there were 17 cardiac events, of which 5 were severe. The difference between
      the 2 groups was highly significant both for severe events (odds ratio: 17.3, 95%
      confidence interval: 3.6 to 82.5) and for all cardiac events (odds ratio: 16.1,
      95% confidence interval: 7.2 to 36.0; both p < 0.001). The rate of all cardiac
      events in patients without obstructive CAD was significantly lower than predicted
      by the Framingham risk score (p = 0.01). CONCLUSIONS: In patients with suspected
      CAD, CCTA has a significant prognostic impact on the prediction of cardiac events
      for the subsequent 18 months. The exclusion of obstructive CAD by CCTA identifies
      a patient population with an event risk lower than predicted by conventional risk
      factors.

PMID- 19580722
TI  - Prospective electrocardiogram-gated delayed enhanced multidetector computed
      tomography accurately quantifies infarct size and reduces radiation exposure.
AB  - OBJECTIVES: This study sought to determine whether low-dose, prospective
      electrocardiogram (ECG)-gated delayed contrast-enhanced multidetector computed
      tomography (DCE-MDCT) can accurately delineate the extent of myocardial
      infarction (MI) compared with retrospective ECG-gated DCE-MDCT. BACKGROUND: For
      defining the location and extent of MI, DCE-MDCT compares well with delayed
      enhanced cardiac magnetic resonance. However, the addition of a delayed scan
      requires additional radiation exposure to patients. MDCT protocols using
      prospective ECG gating can substantially reduce effective radiation dose
      exposure, but these protocols have not yet been applied to infarct imaging.
      METHODS: Ten porcine models of acute MI were imaged 10 days after MI using
      prospective and retrospective ECG-gated DCE-MDCT (64-slice) 10 min after a 90-ml
      contrast bolus. The MDCT images were analyzed using a semiautomated computed
      tomography density (CTD) threshold technique. Infarct size, signal-to-noise (SNR)
      ratios, contrast-to-noise (CNR) ratios, and image quality metrics were compared
      between the 2 ECG-gating techniques. RESULTS: Infarct volume measurements
      obtained by both methods were strongly correlated (R = 0.93, p < 0.001) and in
      good agreement (mean difference: -0.46 ml +/- 4.00%). Compared with retrospective
      ECG gating, estimated radiation dosages were markedly reduced with prospective
      ECG gating (930.1 +/- 62.2 mGy x cm vs. 42.4 +/- 2.3 mGy x cm, p < 0.001). The
      SNR and CNR of infarcted myocardium were somewhat lower for prospective gated
      images (22.0 +/- 11.0 vs. 16.3 +/- 7.8 and 8.8 +/- 5.3 vs. 7.0 +/- 3.9,
      respectively; p < 0.001). However, all examinations using prospective gating
      protocol achieved sufficient diagnostic image quality for the assessment of MI.
      CONCLUSIONS: Prospective ECG-gated DCE-MDCT accurately assesses infarct size
      compared with retrospective ECG-gated DCE-MDCT imaging. Although infarct SNR and
      CNR were significantly higher for the retrospective gated protocol, prospective
      ECG-gated DCE-MDCT provides high-resolution imaging of MI, while substantially
      lowering the radiation dose.

PMID- 19580723
TI  - End of the road for delayed hyperenhancement cardiac magnetic resonance?

PMID- 19580724
TI  - Risk stratification by adenosine stress cardiac magnetic resonance in patients
      with coronary artery stenoses of intermediate angiographic severity.
AB  - OBJECTIVES: The purpose of this study was to determine the role of adenosine
      stress cardiac magnetic resonance (CMR) for risk stratification in patients with
      coronary artery stenoses of intermediate angiographic severity. BACKGROUND:
      Coronary angiography only provides a morphological description of coronary
      lesions. As the patient's prognosis is closely related to the functional
      significance of angiographically detected coronary lesions, a functional
      assessment is desirable in patients with coronary artery stenoses of intermediate
      severity. METHODS: Myocardial perfusion measurements at rest and adenosine stress
      were performed on 81 patients (75.6% male, mean age 64.2 years) with stable
      angina pectoris (AP) and coronary artery stenoses of intermediate angiographic
      severity (50% to 75%). Regardless of the CMR result, all patients were treated
      conservatively with an intensified medical treatment, and a follow-up was
      performed after 18 +/- 8 months and 30 +/- 8 months. The primary end point was
      defined as a major adverse cardiac event (MACE): all-cause death, stroke, acute
      coronary syndrome; the secondary end point was defined as target vessel
      revascularization. Furthermore, AP and dyspnea were evaluated. RESULTS: After the
      follow-up period of 30 +/- 8 months, 9 patients with perfusion deficit (PD)
      suffered from MACE, whereas no MACE occurred among the 36 patients without PD (p
      = 0.014). Among patients who had MACE, the number of ischemic segments (2.3 +/-
      1.6 vs. 1.4 +/- 1.6, p = 0.0025) was significantly higher, whereas the number of
      delayed enhancement segments did not differ (1.4 +/- 1.6 vs. 1.6 +/- 2.3, p =
      0.4). Target vessel revascularization was required in 38% of patients with PD and
      6% of patients without PD (p = 0.005). In addition, the percentage of freedom
      from AP and dyspnea at the follow-up after 18 +/- 8 months was significantly
      lower among patients without perfusion deficit (69.4% vs. 15.6%; p = 0.0001).
      After a follow-up period of 30 +/- 8 months, the rate of AP (11.1% vs. 8.3%, p =
      0.33) as well as the percentage of patients free of symptoms was similar in both
      groups (77.8% vs. 88.9%, p = 0.82). CONCLUSIONS: Adenosine stress CMR may help to
      identify patients at risk who benefit from intensified medical treatment and
      close follow-up.

PMID- 19580725
TI  - Taking the last hurdles: magnetic resonance myocardial perfusion imaging.

PMID- 19580726
TI  - Magnetic resonance adenosine perfusion imaging in patients after coronary artery
      bypass graft surgery.
AB  - OBJECTIVES: The aim of the study was to evaluate the feasibility and diagnostic
      performance of the combination of adenosine stress perfusion and late gadolinium
      enhancement (LGE) in patients after coronary artery bypass graft surgery (CABG).
      BACKGROUND: Cardiac magnetic resonance (CMR) imaging allows the detection of
      significant coronary artery disease by adenosine stress perfusion and infarct
      imaging. Myocardial contrast kinetics may be altered in patients after CABG owing
      to more complex myocardial perfusion and different distances of the contrast
      bolus through different bypasses and native coronary vessels. Additionally, all
      studies have excluded patients after CABG. METHODS: In all, 78 patients (age 66
      +/- 8 years; 71 men) underwent CMR imaging including left ventricular function,
      first-pass adenosine stress perfusion (adenosine 140 microg/min/kg) using 0.05
      mmol/kg body weight gadolinium-diethylenetriaminepenta-acetic acid and an
      additional 0.15 mmol/kg for LGE 1 day before invasive coronary angiography.
      Images were analyzed visually using the speed of contrast wash-in and maximal
      signal intensity. Transmural LGE defects of the size of a vessel or graft
      territory defined by angiography were considered true negatives, even when
      supplied by a stenosed/occluded vessel/graft. Stenoses >50% in grafts and grafted
      or ungrafted native vessels (diameter > or =2 mm) in invasive angiography were
      considered significant. RESULTS: The prevalence of patients with significant
      stenosis was 63% (69% functionally 1-vessel, 28% 2-vessel, and 3% 3-vessel
      disease). Sensitivity and specificity were 77% and 90%, respectively, on a
      patient basis, and 71% and 89% on a vessel territory basis. Sensitivity, if only
      areas supplied by grafts (n = 196) were evaluated, was 78% and specificity was
      94%, compared with territories supplied by ungrafted native vessels (n = 51) with
      sensitivity and specificity of 63% and 91%, respectively. Sensitivity and
      specificity for the 53 areas with prior infarction were 88% and 79%,
      respectively. CONCLUSIONS: For patients after surgical revascularization, the
      combination of stress perfusion and LGE yields good diagnostic accuracy for the
      detection and localization of significant stenoses. However, sensitivity is
      reduced compared with published data in patients without CABG. Prior myocardial
      infarction can be examined without loss of accuracy.

PMID- 19580727
TI  - Noninvasive assessment of coronary artery bypass graft disease: the potential
      role of contrast-enhanced cardiac magnetic resonance.

PMID- 19580728
TI  - Impact of myocardial salvage assessed by (99m)Tc-sestamibi scintigraphy on
      cardiac autonomic function in patients undergoing mechanical reperfusion therapy
      for acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to analyze the impact of myocardial
      salvage on cardiac autonomic function in patients undergoing mechanical
      reperfusion therapy for acute myocardial infarction (MI). BACKGROUND: Heart rate
      deceleration capacity (DC) and heart rate turbulence slope (TS) are strong
      predictors of post-MI mortality. Salvage of jeopardized myocardium is the main
      mechanism by which patients benefit from reperfusion therapy. The impact of
      myocardial salvage on DC and TS is unknown. METHODS: The study enrolled 854
      consecutive patients undergoing mechanical reperfusion therapy for first MI.
      Paired (99m)Tc-sestamibi scintigraphy studies (acute and 7 to 14 days after
      reperfusion) were used to calculate myocardial salvage index. DC and TS were
      assessed from Holter recordings 7 to 14 days after reperfusion. Patients were
      categorized into 3 groups by salvage index: <30% (n = 244), 30% to 60% (n = 257),
      and > or =60% (n = 353). RESULTS: In the 3 groups, DC was 5.2 (interquartile
      range 3.5 to 7.1) ms, 5.7 (4.1 to 7.3) ms, and 6.4 (5.0 to 8.0) ms, whereas TS
      was 5.3 (2.6 to 8.4) ms/R-R interval, 6.9 (3.2 to 11.7) ms/R-R interval, and 7.8
      (4.1 to 13.2) ms/R-R interval, respectively (p < 0.0001 for both). After
      adjustment for left ventricular ejection fraction (LVEF), initial perfusion
      defect, creatine kinase, age, diabetes mellitus, sex, and medical therapy,
      patients with salvage index <30% had a 2.6-fold risk (95% confidence interval:
      1.8 to 3.9, p < 0.001) of having abnormal DC (< or =4.5 ms) or TS (< or =2.5 ms/R
      R interval) compared with patients with salvage index > or =60%. However,
      patients who had autonomic dysfunction defined by abnormal DC and TS had a poor
      prognosis independent of whether or not the salvage index was <30% (5-year
      mortality rates of 16.5% and 17.3%, respectively). In contrast, prognosis was
      excellent when both factors were normal (5-year mortality rates of 2.9% and 4.0%,
      respectively). Predictive value of impaired LVEF (< or =40%) was also independent
      of salvage index. Multivariably, both autonomic dysfunction and impaired LVEF
      were independent predictors of 5-year mortality. CONCLUSIONS: In patients
      undergoing mechanical reperfusion therapy for acute MI, salvage index is an
      independent predictor of autonomic dysfunction but does not affect its prognostic
      value.

PMID- 19580729
TI  - Impact of plaque composition on cardiac troponin elevation after percutaneous
      coronary intervention: an ultrasound analysis.
AB  - OBJECTIVES: We used virtual histology-intravascular ultrasound (VH-IVUS) to study
      the relationship between pre-percutaneous coronary intervention (PCI) coronary
      plaque characteristics and post-PCI cardiac troponin I (cTnI) elevation.
      BACKGROUND: Percutaneous coronary intervention is often complicated by post
      procedural myocardial necrosis as manifested by elevated cardiac markers.
      METHODS: Eighty consecutive patients (29 stable and 51 unstable angina) with
      normal pre-PCI cTnI levels were imaged before PCI using VH-IVUS. Patients were
      divided into 2 groups according to the presence (Group I, n = 38) or absence
      (Group II, n = 42) of post-PCI cTnI elevation > or =3x the upper limit of normal
      (0.08 ng/ml). RESULTS: The absolute and percent necrotic core volumes were
      significantly greater in Group I than in Group II (13.6 +/- 6.4 mm(3) vs. 7.9 +/-
      4.4 mm(3), p < 0.001, and 19.8 +/- 10.4% vs. 12.8 +/- 8.4%, p = 0.015,
      respectively). The absolute and percent necrotic core areas were significantly
      greater in Group I than in Group II at the minimum lumen site (1.70 +/- 0.91
      mm(2) vs. 0.61 +/- 0.39 mm(2), p < 0.001, and 22.9 +/- 11.7% vs. 10.4 +/- 6.6%, p
      < 0.001, respectively) and at the largest necrotic core site (2.00 +/- 0.86 mm(2)
      vs. 0.81 +/- 0.78 mm(2), p < 0.001, and 24.0 +/- 11.7% vs. 12.9 +/- 6.6%, p <
      0.001, respectively). The DeltacTnI correlated with: 1) absolute and percent
      necrotic core area at the minimum lumen site and at the largest necrotic core
      site; 2) absolute necrotic core volume; 3) percent fibrofatty area at the minimum
      lumen site; and 4) lesion site plaque burden. In the multivariate analysis,
      absolute necrotic core area at the minimum lumen site was the only independent
      predictor of post-PCI cTnI elevation > or =3x the upper limit of normal (odds
      ratio: 1.318; 95% confidence interval: 1.090 to 1.594, p = 0.004). CONCLUSIONS:
      The VH-IVUS analysis shows that post-PCI cTnI elevation occurs in lesions with a
      large necrotic core area. The VH-IVUS may play an important role in detecting
      which lesions are high risks for myocardial necrosis after PCI.

PMID- 19580730
TI  - Intravascular ultrasound tissue characterization: messages from the heart.

PMID- 19580731
TI  - In vivo assessment of high-risk coronary plaques at bifurcations with combined
      intravascular ultrasound and optical coherence tomography.
AB  - OBJECTIVES: This study sought to evaluate the in vivo frequency and distribution
      of high-risk plaques (i.e., necrotic core rich) at bifurcations using a combined
      plaque assessment with intravascular ultrasound-virtual histology (IVUS-VH) and
      optical coherence tomography (OCT). BACKGROUND: Pathological examinations have
      shown that atherosclerotic plaque rich in necrotic core is prone to develop at
      bifurcations. High-risk plaque detection could be improved by the combined use of
      a technique able to detect necrotic core (IVUS-VH) and a high-resolution
      technique that allows the measurement of the fibrous cap thickness (OCT).
      METHODS: From 30 patients imaged with IVUS-VH and OCT, 103 bifurcations were
      selected. The main branch was analyzed at the proximal rim of the ostium of the
      side branch, at the in-bifurcation segment and at the distal rim of the ostium of
      the side branch. Plaques with more than 10% confluent necrotic core by IVUS-VH
      were selected and classified as fibroatheroma (FA) or thin-cap fibroatheroma
      (TCFA) depending on the thickness of the fibrous cap by OCT (>65 or < or =65
      microm for FA and TCFA, respectively). RESULTS: Twenty-seven FA (26.2%) and 18
      TCFA (17.4%) were found out of the 103 lesions studied. Overall the percentage of
      necrotic core decreases from proximal to distal rim (16.8% vs. 13.5%
      respectively, p = 0.01), whereas the cap thickness showed an inverse tendency
      (130 +/- 105 microm vs. 151 +/- 68 microm for proximal and distal rim,
      respectively, p = 0.05). The thin caps were more often located in the proximal
      rim (15 of 34, 44.1%), followed by the in-bifurcation segment (14 of 34, 41.2%),
      and were less frequent in the distal rim (5 of 34, 14.7%). CONCLUSIONS: The
      proximal rim of the ostium of the side branch has been identified as a region
      more likely to contain thin fibrous cap and a greater proportion of necrotic
      core.

PMID- 19580732
TI  - The vulnerable plaque "hypothesis": promise, but little progress.

PMID- 19580733
TI  - Imaging cardiac resynchronization therapy.
AB  - Although a prognostic benefit has been shown from cardiac resynchronization
      therapy, questions are often directed toward the prediction of symptomatic or
      functional benefit. Recent multicenter trials have shown the pitfalls of current
      mechanical markers of left ventricular synchrony, but these negative trial
      results have not marked the conclusion of efforts to predict outcome. Potential
      new contributors to the assessment of mechanical synchrony include
      echocardiographic and magnetic resonance techniques for the assessment of
      myocardial deformation. Nonsynchrony markers that seem promising include
      assessment of the location and extent of myocardial scar and imaging of the
      coronary venous and phrenic nerve anatomy.

PMID- 19580734
TI  - The year in imaging related to electrophysiology.

PMID- 19580736
TI  - Contribution of noninvasive imaging to the diagnosis and follow-up of Takotsubo
      cardiomyopathy.

PMID- 19580735
TI  - Treatment of acute intravascular thrombi with diagnostic ultrasound and
      intravenous microbubbles.
AB  - The purpose of this study was to determine whether high mechanical index (MI)
      impulses from diagnostic ultrasound (DUS) could dissolve intravascular thrombi
      using intravenous microbubbles. Using a canine model, DUS was applied during a
      continuous intravenous infusion of microbubbles. Completely thrombosed grafts
      were assigned to 2 treatment regimens: low-MI (<0.5-MI) ultrasound alone; or
      intermittent high-MI impulses (1.9-MI) guided by low-MI ultrasound (contrast
      pulse sequencing). A 20-MHz cavitation detector was placed confocal to the
      ultrasound transducer to make intravascular cavitation measurements in 1 dog.
      Intravascular cavitational activity was detected when an MI of >0.5 was applied.
      In grafts treated with intermittent high-MI ultrasound, angiographic success was
      71% at 30 min and 79% at 45 min, compared with 20% and 30% at these times in the
      low-MI ultrasound alone group (p < 0.05). We conclude that a commercially
      available DUS transducer can successfully recanalize acute intravascular thrombi
      during a continuous microbubble infusion.

PMID- 19580737
TI  - Percutaneous valve-in-valve procedure for severe paravalvular regurgitation in
      aortic bioprosthesis.

PMID- 19580738
TI  - Bridging the detection gap chasm of risk: where can computed tomography
      angiography take us?

PMID- 19580739
TI  - Thermodynamic description of polymorphism in Q- and N-rich peptide aggregates
      revealed by atomistic simulation.
AB  - Amyloid fibrils are long, helically symmetric protein aggregates that can display
      substantial variation (polymorphism), including alterations in twist and
      structure at the beta-strand and protofilament levels, even when grown under the
      same experimental conditions. The structural and thermodynamic origins of this
      behavior are not yet understood. We performed molecular-dynamics simulations to
      determine the thermodynamic properties of different polymorphs of the peptide
      GNNQQNY, modeling fibrils containing different numbers of protofilaments based on
      the structure of amyloid-like cross-beta crystals of this peptide. We also
      modeled fibrils with new orientations of the side chains, as well as a de novo
      designed structure based on antiparallel beta-strands. The simulations show that
      these polymorphs are approximately isoenergetic under a range of conditions.
      Structural analysis reveals a dynamic reorganization of electrostatics and
      hydrogen bonding in the main and side chains of the Gln and Asn residues that
      characterize this peptide sequence. Q/N-rich stretches are found in several
      amyloidogenic proteins and peptides, including the yeast prions Sup35-N and
      Ure2p, as well as in the human poly-Q disease proteins, including the ataxins and
      huntingtin. Based on our results, we propose that these residues imbue a unique
      structural plasticity to the amyloid fibrils that they comprise, rationalizing
      the ability of proteins enriched in these amino acids to form prion strains with
      heritable and different phenotypic traits.

PMID- 19580740
TI  - Atomistic modeling of macromolecular crowding predicts modest increases in
      protein folding and binding stability.
AB  - Theoretical models predict that macromolecular crowding can increase protein
      folding stability, but depending on details of the models (e.g., how the
      denatured state is represented), the level of stabilization predicted can be very
      different. In this study, we represented the native and denatured states
      atomistically, with conformations sampled from explicit-solvent molecular
      dynamics simulations at room temperature and high temperature, respectively. We
      then designed an efficient algorithm to calculate the allowed fraction, f, when
      the protein molecule is placed inside a box of crowders. That a fraction of
      placements of the protein molecule is disallowed because of volume exclusion by
      the crowders leads to an increase in chemical potential, given by Deltamu = 
      k(B)T lnf. The difference in Deltamu between the native and denatured states
      predicts the effect of crowding on the folding free energy. Even when the
      crowders occupied 35% of the solution volume, the stabilization reached only 1.5
      kcal/mol for cytochrome b562. The modest stabilization predicted is consistent
      with experimental studies. Interestingly, a mixture of different sized crowders
      was found to exert a greater effect than the sum of the individual species of
      crowders. The stabilization of crowding on the binding stability of barnase and
      barstar, based on atomistic modeling of the proteins, was similarly modest. These
      findings have profound implications for macromolecular crowding inside cells.

PMID- 19580741
TI  - Optimal velocity and safety of discontinuous conduction through the heterogeneous
      Purkinje-ventricular junction.
AB  - Slow and discontinuous wave conduction through nonuniform junctions in cardiac
      tissues is generally considered unsafe and proarrythmogenic. However, the
      relationships between tissue structure, wave conduction velocity, and safety at
      such junctions are unknown. We have developed a structurally and
      electrophysiologically detailed model of the canine Purkinje-ventricular junction
      (PVJ) and varied its heterogeneity parameters to determine such relationships. We
      show that neither very fast nor very slow conduction is safe, and there exists an
      optimal velocity that provides the maximum safety factor for conduction through
      the junction. The resultant conduction time delay across the PVJ is a natural
      consequence of the electrophysiological and morphological differences between the
      Purkinje fiber and ventricular tissue. The delay allows the PVJ to accumulate and
      pass sufficient charge to excite the adjacent ventricular tissue, but is not long
      enough for the source-to-load mismatch at the junction to be enhanced over time.
      The observed relationships between the conduction velocity and safety factor can
      provide new insights into optimal conditions for wave propagation through
      nonuniform junctions between various cardiac tissues.

PMID- 19580742
TI  - Alternative mechanisms for the interaction of the cell-penetrating peptides
      penetratin and the TAT peptide with lipid bilayers.
AB  - Cell-penetrating peptides (CPPs) have recently attracted much interest due to
      their apparent ability to penetrate cell membranes in an energy-independent
      manner. Here molecular-dynamics simulation techniques were used to study the
      interaction of two CPPs: penetratin and the TAT peptide with 1,2-Dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC) phospolipid bilayers shed light on alternative mechanisms by which these
      peptides might cross biological membranes. In contrast to previous simulation
      studies of charged peptides interacting with lipid bilayers, no spontaneous
      formation of transmembrane pores was observed. Instead, the simulations suggest
      that the peptides may enter the cell by micropinocytosis, whereby the peptides
      induce curvature in the membrane, ultimately leading to the formation of small
      vesicles within the cell that encapsulate the peptides. Specifically, multiple
      peptides were observed to induce large deformations in the lipid bilayer that
      persisted throughout the timescale of the simulations (hundreds of nanoseconds).
      Pore formation could be induced in simulations in which an external potential was
      used to pull a single penetratin or TAT peptide into the membrane. With the use
      of umbrella-sampling techniques, the free energy of inserting a single penetratin
      peptide into a DPPC bilayer was estimated to be approximately 75 kJmol(-1), which
      suggests that the spontaneous penetration of single peptides would require a
      timescale of at least seconds to minutes. This work also illustrates the extent
      to which the results of such simulations can depend on the initial conditions,
      the extent of equilibration, the size of the system, and the conditions under
      which the simulations are performed. The implications of this with respect to the
      current systems and to simulations of membrane-peptide interactions in general
      are discussed.

PMID- 19580743
TI  - CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast
      membranes.
AB  - The CHARMM-GUI Membrane Builder (http://www.charmm-gui.org/input/membrane), an
      intuitive, straightforward, web-based graphical user interface, was expanded to
      automate the building process of heterogeneous lipid bilayers, with or without a
      protein and with support for up to 32 different lipid types. The efficacy of
      these new features was tested by building and simulating lipid bilayers that
      resemble yeast membranes, composed of cholesterol,
      dipalmitoylphosphatidylcholine, dioleoylphosphatidylcholine,
      palmitoyloleoylphosphatidylethanolamine, palmitoyloleoylphosphatidylamine, and
      palmitoyloleoylphosphatidylserine. Four membranes with varying concentrations of
      cholesterol and phospholipids were simulated, for a total of 170 ns at 303.15 K.
      Unsaturated phospholipid chain concentration had the largest influence on
      membrane properties, such as average lipid surface area, density profiles,
      deuterium order parameters, and cholesterol tilt angle. Simulations with a high
      concentration of unsaturated chains (73%, membrane(unsat)) resulted in a
      significant increase in lipid surface area and a decrease in deuterium order
      parameters, compared with membranes with a high concentration of saturated chains
      (60-63%, membrane(sat)). The average tilt angle of cholesterol with respect to
      bilayer normal was largest, and the distribution was significantly broader for
      membrane(unsat). Moreover, short-lived cholesterol orientations parallel to the
      membrane surface existed only for membrane(unsat). The membrane(sat) simulations
      were in a liquid-ordered state, and agree with similar experimental cholesterol
      containing membranes.

PMID- 19580744
TI  - Phase resetting curves allow for simple and accurate prediction of robust N:1
      phase locking for strongly coupled neural oscillators.
AB  - Existence and stability criteria for harmonic locking modes were derived for two
      reciprocally pulse coupled oscillators based on their first and second order
      phase resetting curves. Our theoretical methods are general in the sense that no
      assumptions about the strength of coupling, type of synaptic coupling, and model
      are made. These methods were then tested using two reciprocally inhibitory Wang
      and Buzsaki model neurons. The existence of bands of 2:1, 3:1, 4:1, and 5:1 phase
      locking in the relative frequency parameter space was predicted correctly, as was
      the phase of the slow neuron's spike within the cycle of the fast neuron in which
      it occurred. For weak coupling the bands are very narrow, but strong coupling
      broadens the bands. The predictions of the pulse coupled method agreed with weak
      coupling methods in the weak coupling regime, but extended predictability into
      the strong coupling regime. We show that our prediction method generalizes to
      pairs of neural oscillators coupled through excitatory synapses, and to networks
      of multiple oscillatory neurons. The main limitation of the method is the central
      assumption that the effect of each input dies out before the next input is
      received.

PMID- 19580745
TI  - A mechanism for precision-sensing via a gradient-sensing pathway: a model of
      Escherichia coli thermotaxis.
AB  - Thermotaxis is the phenomenon where an organism directs its movement toward its
      preferred temperature. So far, the molecular origin for this precision-sensing
      behavior remains a puzzle. We propose a model of Escherichia coli thermotaxis and
      show that the precision-sensing behavior in E. coli thermotaxis can be carried
      out by the gradient-sensing chemotaxis pathway under two general conditions.
      First, the thermosensor response to temperature is inverted by its internal
      adaptation state. For E. coli, chemoreceptor Tar changes from a warm sensor to a
      cold sensor on increase of its methylation level. Second, temperature directly
      affects the adaptation kinetics. The adapted activity in E. coli increases with
      temperature in contrast to the perfect adaptation to chemical stimuli. Given
      these two conditions, E. coli thermotaxis is achieved by the cryophilic and
      thermophilic responses for temperature above and below a critical temperature Tc,
      which is encoded by internal pathway parameters. Our model results are supported
      by both experiments with adaptation-disabled mutants and the recent temperature
      impulse response measurements for wild-type cells. Tc is predicted to decrease
      with the background attractant concentration. This mechanism for precision
      sensing in an adaptive gradient-sensing system may apply to other organisms, such
      as Dictyostelium discoideum and Caenorhabditis elegans.

PMID- 19580746
TI  - Structural and viscoelastic properties of actin/filamin networks: cross-linked
      versus bundled networks.
AB  - The high diversity of cytoskeletal actin structures is accomplished by myriads of
      actin binding proteins (ABPs). Depending on its concentration, even a single type
      of ABP can induce different actin microstructures. Thus, for an overall
      understanding of the cytoskeleton, a detailed characterization of the cross
      linker's effect on structural and mechanical properties of actin networks is
      required for each ABP. Using confocal microscopy and macrorheology, we
      investigate both cross-linked and bundled actin/filamin networks and compare
      their microstructures as well as their viscoelastic properties in the linear and
      the nonlinear regime.

PMID- 19580747
TI  - Coupling of S4 helix translocation and S6 gating analyzed by molecular-dynamics
      simulations of mutated Kv channels.
AB  - The recently determined crystal structure of a chimeric Kv1.2-Kv2.1 Kv channel at
      2.4 A resolution motivated this molecular-dynamics simulation study of the
      chimeric channel and its mutants embedded in a DPPC membrane. For the channel
      protein, we used two types of C-terminus: E+ and Eo. E+ contains, and Eo lacks,
      the EGEE residue quartet located distal to the S6 helix. For both E+ and Eo, the
      following trend was observed: When S4 helices were restrained at the same
      position as in the x-ray structure (S4high), the S6 gate remained open for 12 ns.
      The results were similar when the S4 helices were pulled downward 7 A (S4low).
      However, S4middle (or S4low) facilitated the S6 gate-narrowing for the following
      mutated channels (shown in order of increasing effect): 1), E395W; 2), E395W
      F401A-F402A; and 3), E395W-F401A-F402A-V478W. The amino acid numbering system is
      that used for the Shaker channel. Even though all four subunits were set at
      S4low, S6 gate-narrowing was often brought about by movements of only two
      opposing S6 helices toward the central axis of the pore, resulting in a twofold
      symmetry-like structure. A free-energy profile analysis over the ion conduction
      pathway shows that the two opposing S6 helices whose peptide backbones are
      approximately 10.4 A distant from each other lead to an energetic barrier of
      approximately 25 kJ/mol. S6 movement was coupled with translocation of the S4-S5
      linker toward the central axis of the same subunit, and the coupling was mediated
      by salt bridges formed between the inner (intracellular side) end of S4 and that
      of S6. Simulations in which S4 of only one subunit was pulled down to S4low
      showed that a weak intersubunit coordination is present for S5 movement, whereas
      the coupling between the S4-S5 linker and S6 is largely an intrasubunit one. In
      general, whereas subunit-based behavior appears to be dominant and to permit
      heteromeric conformations of the pore domain, direct intersubunit coupling of S5
      or S6 is weak. Therefore, the "concerted transition" of the pore domain that has
      been predicted based on electrophysiological analyses is likely to be mediated
      mainly by the dual effects of S4 and the S4-S5 linker; these segments of one
      subunit can interact with both S5 of the same subunit and that of the adjacent
      subunit.

PMID- 19580748
TI  - Biophysical characterization of styryl dye-membrane interactions.
AB  - Styryl dyes (also referred to as FM dyes) become highly fluorescent upon binding
      to membranes and are often used to study synaptic vesicle recycling in neurons.
      To date, however, no direct comparisons of the fluorescent properties, or time
      resolved (millisecond) measurements of dye-membrane binding and unbinding
      reactions, for all members of this family of probes have been reported. Here, we
      compare the fluorescence intensities of each member of the FM dye family when
      bound to membranes. This analysis included SGC5, a new lipophilic fluorescent dye
      with a unique structure. Fluorescence intensities depended on the length of the
      lipophilic tail of each dye, with a rank order as follows: SGC5 > FM1-84 > FM1-43
      > SynaptoGreen C3 > FM2-10/FM4-64/FM5-95. Stopped-flow measurements revealed that
      dye hydrophobicity determined the affinity and departitioning rates for dye
      membrane interactions. All of the dyes dissociated from membranes on the
      millisecond timescale, which is orders of magnitude faster than the overall
      destaining rate (timescale of seconds) of these dyes from presynaptic boutons.
      Departitioning kinetics were faster at higher temperatures, but were unaffected
      by pH or cholesterol. The data reported here aid interpretation of dye-release
      kinetics from single synaptic vesicles, and indicate that these probes dissociate
      from membranes on more rapid timescales than previously appreciated.

PMID- 19580750
TI  - Proton transport pathway in the ClC Cl-/H+ antiporter.
AB  - A fundamental question concerning the ClC Cl-/H+ antiporters is the nature of
      their proton transport (PT) pathway. We addressed this issue by using a novel
      computational methodology capable of describing the explicit PT dynamics in the
      ClC-ec1 protein. The main result is that the Glu203 residue delivers a proton
      from the intracellular solution to the core of ClC-ec1 via a rotation of its side
      chain and subsequent acid dissociation. After reorientation of the Glu203 side
      chain, a transient water-mediated PT pathway between Glu203 and Glu148 is
      established that is able to receive and translocate the proton via Grotthuss
      shuttling after deprotonation of Glu203. A molecular-dynamics simulation of an
      explicit hydrated excess proton in this pathway suggests that a negatively
      charged Glu148 and the central Cl- ion act together to drive H+ to the
      extracellular side of the membrane. This finding is consistent with the
      experimental result that Cl- binding to the central site facilitates the proton
      movement. A calculation of the PT free-energy barrier for the ClC-ec1 E203V
      mutant also supports the proposal that a dissociable residue is required at this
      position for efficient delivery of H+ to the protein interior, in agreement with
      recent experimental results.

PMID- 19580749
TI  - Divalent cations slow activation of EAG family K+ channels through direct binding
      to S4.
AB  - Voltage-gated K+ channels share a common voltage sensor domain (VSD) consisting
      of four transmembrane helices, including a highly mobile S4 helix that contains
      the major gating charges. Activation of ether-a-go-go (EAG) family K+ channels is
      sensitive to external divalent cations. We show here that divalent cations slow
      the activation rate of two EAG family channels (Kv12.1 and Kv10.2) by forming a
      bridge between a residue in the S4 helix and acidic residues in S2. Histidine 328
      in the S4 of Kv12.1 favors binding of Zn2+ and Cd2+, whereas the homologous
      residue Serine 321 in Kv10.2 contributes to effects of Mg2+ and Ni2+. This novel
      finding provides structural constraints for the position of transmembrane VSD
      helices in closed, ion-bound EAG family channels. Homology models of Kv12.1 and
      Kv10.2 VSD structures based on a closed-state model of the Shaker family K+
      channel Kv1.2 match these constraints. Our results suggest close conformational
      conservation between closed EAG and Shaker family channels, despite large
      differences in voltage sensitivity, activation rates, and activation thresholds.

PMID- 19580751
TI  - Phospholipid reorientation at the lipid/water interface measured by high
      resolution 31P field cycling NMR spectroscopy.
AB  - The magnetic field dependence of the 31P spin-lattice relaxation rate, R1, of
      phospholipids can be used to differentiate motions for these molecules in a
      variety of unilamellar vesicles. In particular, internal motion with a 5- to 10
      ns correlation time has been attributed to diffusion-in-a-cone of the
      phosphodiester region, analogous to motion of a cylinder in a liquid hydrocarbon.
      We use the temperature dependence of 31P R1 at low field (0.03-0.08 T), which
      reflects this correlation time, to explore the energy barriers associated with
      this motion. Most phospholipids exhibit a similar energy barrier of 13.2 +/- 1.9
      kJ/mol at temperatures above that associated with their gel-to-liquid-crystalline
      transition (Tm); at temperatures below Tm, this barrier increases dramatically to
      68.5 +/- 7.3 kJ/mol. This temperature dependence is broadly interpreted as
      arising from diffusive motion of the lipid axis in a spatially rough potential
      energy landscape. The inclusion of cholesterol in these vesicles has only
      moderate effects for phospholipids at temperatures above their Tm, but
      significantly reduces the energy barrier (to 17 +/- 4 kJ/mol) at temperatures
      below the Tm of the pure lipid. Very-low-field R1 data indicate that cholesterol
      inclusion alters the averaged disposition of the phosphorus-to-glycerol-proton
      vector (both its average length and its average angle with respect to the
      membrane normal) that determines the 31P relaxation.

PMID- 19580752
TI  - Direct visualization of the lateral structure of porcine brain cerebrosides/POPC
      mixtures in presence and absence of cholesterol.
AB  - We studied the thermal behavior of membranes composed of mixtures of natural
      cerebrosides (from porcine brain) and 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) with and without cholesterol, using differential scanning
      calorimetry, Fourier transform infrared spectroscopy, and confocal/multiphoton
      fluorescence microscopy. The POPC/cerebroside mixture display solid
      ordered/liquid disordered phase coexistence in a broad range of compositions and
      temperatures in agreement with previous results reported for POPC/(bovine
      brain)cerebrosides. The observed phase coexistence scenario consists of
      elongated, micrometer-sized cerebroside-rich solid ordered domains that span the
      bilayer, embedded in a POPC-rich liquid disordered phase. The data obtained from
      differential scanning calorimetry and Fourier transform infrared spectroscopy was
      in line with that obtained in the microscopy experiments for the binary mixture,
      except at very high cerebroside molar fractions (0.8-0.9) were some differences
      are observed. Cholesterol incorporation exerts strong changes on the lateral
      organization of POPC/porcine brain cerebroside membranes. At intermediate
      cholesterol concentrations (10-25 mol %) the solid ordered/liquid disordered
      phase coexistence scenario gradually transform to a solid ordered/liquid ordered
      one. Above 25 mol % of cholesterol two distinct regions with liquid ordered phase
      character are visualized in the membrane until a single liquid ordered phase
      forms at 40 mol % cholesterol. The observed cholesterol effect largely differs
      from that reported for POPC/porcine brain ceramide, reflecting the impact of the
      sphingolipids polar headgroup on the membrane lateral organization.

PMID- 19580753
TI  - Molecular dynamics simulations of PIP2 and PIP3 in lipid bilayers: determination
      of ring orientation, and the effects of surface roughness on a Poisson-Boltzmann
      description.
AB  - Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate
      (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2
      oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are
      tilted approximately 40 degrees with respect to the bilayer surface, as compared
      with 17 degrees for the P-N vector of POPC. Multiple minima were obtained for the
      ring twist (analogous to roll for an airplane). The phosphates at position 1 of
      PIP2 and PIP3 are within an Angstrom of the plane formed by the phosphates of
      POPC; lipids in the surrounding shell are depressed by 0.5-0.8 A, but otherwise
      the phosphoinositides do not substantially perturb the bilayer. Finite size
      artifacts for ion distributions are apparent for systems of approximately 26
      waters/lipid, but, based on simulations with a fourfold increase of the aqueous
      phase, the phosphoinositide positions and orientations do not show significant
      size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB)
      calculations show a strong dependence of potential height and ring orientation,
      with the maxima on the -25 mV surfaces (17.1 +/- 0.1 A for PIP2 and 19.4 +/- 0.3
      A for PIP3) occurring near the most populated orientations from MD. These
      surfaces are well above the background height of 10 A estimated for negatively
      charged cell membranes, as would be expected for lipids involved in cellular
      signaling. PB calculations on microscopically flat bilayers yield similar maxima
      as the MD-based (microscopically rough) systems, but show less fine structure and
      do not clearly indicate the most probable regions. Electrostatic free energies of
      interaction with pentalysine are also similar for the rough and flat systems.
      These results support the utility of a rigid/flat bilayer model for PB-based
      studies of PIP2 and PIP3 as long as the orientations are judiciously chosen.

PMID- 19580754
TI  - Characterization of antibiotic peptide pores using cryo-EM and comparison to
      neutron scattering.
AB  - Magainin, a 23-residue antibiotic peptide, interacts directly with the lipid
      bilayer leading to cell lysis in a strongly concentration-dependent fashion.
      Utilizing cryo-electron microscopy, we have directly observed magainin
      interacting with synthetic DMPC/DMPG membranes. Visual examination shows that
      visibly unperturbed vesicles are often found adjacent to vesicles that are lysed
      or porous, demonstrating that magainin disruption is a highly stochastic process.
      Quantitatively, power spectra of large numbers of porous vesicles can be averaged
      together to produce the equivalent of an electron scattering curve, which can be
      related to theory, simulation, and published neutron scattering experiments. We
      demonstrate that magainin-induced pores in lipid vesicles have a mean diameter of
      approximately 80 A, compatible with earlier reported results in multilayer
      stacks. In addition to establishing a connection between experiments in
      multilayer stacks and vesicles, this also demonstrates that computed power
      spectra from windowed-out regions of cryo-EM images can be compared to neutron
      scattering data in a meaningful way, even though the pores of interest cannot yet
      be individually identified in images. Cryo-EM offers direct imaging of systems in
      configurations closely related to in vivo conditions, whereas neutron scattering
      has a greater variety of mechanisms for specific contrast variation via D2O and
      deuterated lipids. Combined, the two mechanisms support each other, and provide a
      clearer picture of such 'soft' systems than either could provide alone.

PMID- 19580755
TI  - Alternating-site mechanism of kinesin-1 characterized by single-molecule FRET
      using fluorescent ATP analogues.
AB  - Kinesin-1 motor proteins move along microtubules in repetitive steps of 8 nm at
      the expense of ATP. To determine nucleotide dwell times during these processive
      runs, we used a Forster resonance energy transfer method at the single-molecule
      level that detects nucleotide binding to kinesin motor heads. We show that the
      fluorescent ATP analog used produces processive motility with kinetic parameters
      altered <2.5-fold compared with normal ATP. Using our confocal fluorescence
      kinesin motility assay, we obtained fluorescence intensity time traces that we
      then analyzed using autocorrelation techniques, yielding a time resolution of
      approximately 1 ms for the intensity fluctuations due to fluorescent nucleotide
      binding and release. To compare these experimental autocorrelation curves with
      kinetic models, we used Monte-Carlo simulations. We find that the experimental
      data can only be described satisfactorily on the basis of models assuming an
      alternating-site mechanism, thus supporting the view that kinesin's two motor
      domains hydrolyze ATP and step in a sequential way.

PMID- 19580757
TI  - spFRET using alternating excitation and FCS reveals progressive DNA unwrapping in
      nucleosomes.
AB  - Accessibility to DNA wrapped in nucleosomes is essential for nuclear processes
      such as DNA transcription. Large conformational changes in nucleosome structure
      are required to facilitate protein binding to target sites within nucleosomal
      DNA. Transient unwrapping of DNA from nucleosome ends can provide an intrinsic
      exposure of wrapped DNA, allowing proteins to bind DNA that would otherwise be
      occluded in the nucleosome. The molecular details underlying these mechanisms
      remain to be resolved. Here we show how DNA unwrapping occurs progressively from
      both nucleosome ends. We performed single-pair fluorescence resonance energy
      transfer (spFRET) spectroscopy with alternating laser excitation (ALEX) on
      nucleosomes either in free solution or confined in a gel after PAGE separation.
      We combined ALEX-spFRET with a correlation analysis on selected bursts of
      fluorescence, to resolve a variety of unwrapped nucleosome conformations. The
      experiments reveal that nucleosomes are unwrapped with an equilibrium constant of
      approximately 0.2-0.6 at nucleosome ends and approximately 0.1 at a location 27
      basepairs inside the nucleosome, but still remain stably associated. Our
      findings, obtained using a powerful combination of single-molecule fluorescence
      techniques and gel electrophoresis, emphasize the delicate interplay between DNA
      accessibility and condensation in chromatin.

PMID- 19580756
TI  - Differences between cardiac and skeletal troponin interaction with the thin
      filament probed by troponin exchange in skeletal myofibrils.
AB  - Troponin (Tn) is the calcium-sensing protein of the thin filament. Although
      cardiac troponin (cTn) and skeletal troponin (sTn) accomplish the same function,
      their subunit interactions within Tn and with actin-tropomyosin are different. To
      further characterize these differences, myofibril ATPase activity as a function
      of pCa and labeled Tn exchange in rigor myofibrils was used to estimate Tn
      dissociation rates from the nonoverlap and overlap region as a function of pCa.
      Measurement of ATPase activity showed that skeletal myofibrils containing >96%
      cTn had a higher pCa 9 ATPase activity than, but similar pCa 4 activity to, sTn
      containing myofibrils. Analysis of the pCa-ATPase activity relation showed that
      cTn myofibrils were more calcium sensitive but less cooperative (pCa50 = 6.14, nH
      = 1.46) than sTn myofibrils (pCa50= 5.90, nH = 3.36). The time course of labeled
      Tn exchange at pCa 9 and 4 were quite different between cTn and sTn. The apparent
      cTn dissociation rates were approximately 2-10-fold faster than sTn under all the
      conditions studied. The apparent dissociation rates for cTn were 5 x 10(-3) min(
      1), 150 x 10(-3) min(-1), and 260 x 10(-3) min(-1), whereas for sTn they were 0.6
      x 10(-3) min(-1), 88 x 10(-3) min(-1), and 68 x 10(-3) min(-1) for the nonoverlap
      region at pCa 9, nonoverlap region at pCa 4, and overlap region at pCa 4,
      respectively. Normalization of the apparent dissociation rates gives 1:30:50 for
      cTn compared with 1:150:110 for sTn (nonoverlap at pCa 9:nonoverlap at pCa
      4:overlap at pCa 4) suggesting that calcium has a smaller influence, whereas
      strong cross-bridges have a larger influence on cTn dissociation compared with
      sTn. The higher cTn dissociation rate in the nonoverlap region and ATPase
      activity at pCa 9 suggest that it gives a less off or inactive thin filament.
      Analysis of the intensity ratio (after a short time of exchange) as a function of
      pCa showed that cTn had greater calcium sensitivity but lower cooperativity than
      sTn. In addition, the magnitude of the change in intensity ratio going from pCa 9
      to 4 was less for cTn than sTn. These data suggest that the influence of calcium
      on cTn exchange is less than sTn even though calcium can activate ATPase activity
      to a similar extent in cTn compared with sTn myofibrils. This may be explained
      partially by cTn being less off or inactive at pCa 9. Modeling of the intensity
      profiles obtained after Tn exchange at pCa 5.8 suggest that the profiles are best
      explained by a model that includes a long-range cross-bridge effect that grades
      with distance from the rigor cross-bridge for both cTn and sTn.

PMID- 19580758
TI  - The length and viscosity dependence of end-to-end collision rates in single
      stranded DNA.
AB  - Intramolecular dynamics play an essential role in the folding and function of
      biomolecules and, increasingly, in the operation of many biomimetic technologies.
      Thus motivated we have employed both experiment and simulation to characterize
      the end-to-end collision dynamics of unstructured, single-stranded DNAs ranging
      from 6 to 26 bases. We find that, because of the size and flexibility of the
      optical reporters employed experimentally, end-to-end collision dynamics exhibit
      little length dependence at length scales <11 bases. For longer constructs,
      however, the end-to-end collision rate exhibits a power-law relationship to
      polymer length with an exponent of -3.49 +/- 0.13. This represents a
      significantly stronger length dependence than observed experimentally for
      unstructured polypeptides or predicted by polymer scaling arguments. Simulations
      indicate, however, that the larger exponent stems from electrostatic effects that
      become important over the rather short length scale of these highly charged
      polymers. Finally, we have found that the end-to-end collision rate also depends
      linearly on solvent viscosity, with an experimentally significant, nonzero
      intercept (the extrapolated rate at zero viscosity) that is independent of chain
      length--n observation that sheds new light on the origins of the "internal
      friction" observed in the dynamics of many polymer systems.

PMID- 19580759
TI  - Flash photolysis of cutinase: identification and decay kinetics of transient
      intermediates formed upon UV excitation of aromatic residues.
AB  - Aromatic amino acids play an important role in ultraviolet (UV)-induced
      photochemical reactions in proteins. In this work, we aim at gaining insight into
      the photochemical reactions induced by near-UV light excitation of aromatic
      residues that lead to breakage of disulfide bridges in our model enzyme, Fusarium
      solani pisi cutinase, a lipolytic enzyme. With this purpose, we acquired
      transient absorption data of cutinase, with supplemental experimental data on
      tryptophan (Trp) and lysozyme as reference molecules. We here report formation
      kinetics and lifetimes of transient chemical species created upon UV excitation
      of aromatic residues in proteins. Two proteins, lysozyme and cutinase, as well as
      the free amino acid Trp, were studied under acidic, neutral, and alkaline
      conditions. The shortest-lived species is assigned to solvated electrons
      (lifetimes of a few microseconds to nanoseconds), whereas the longer-lived
      species are assigned to aromatic neutral and ionic radicals, Trp triplet states,
      and radical ionic disulphide bridges. The pH-dependent lifetimes of each species
      are reported. Solvated electrons ejected from the side chain of free Trp residues
      and aromatic residues in proteins were observed 12 ns after excitation, reaching
      a maximum yield after approximately 40 ns. It is interesting to note that the
      formation kinetics of solvated electrons is not pH-dependent and is similar in
      the different samples. On the other hand, a clear increase of the solvated
      electron lifetime is observed with increasing pH. This observation is correlated
      with H3O+ being an electron scavenger. Prolonged UV illumination of cutinase
      leads to a larger concentration of solvated electrons and to greater absorption
      at 410 nm (assigned to disulphide electron adduct RSSR *-), with concomitant
      faster decay kinetics and near disappearance of the Trp* radical peak at 330 nm,
      indicating possible additional formation of TyrO* formed upon reaction of Trp*
      with Tyr residues. Prolonged UV illumination of cutinase also leads to a larger
      concentration of free thiol groups, known to originate from the dissociation of
      RSSR *-. Additional mechanisms that may lead to the near disappearance of Trp(*)
      are discussed. Our study provides insight into one key UV-light-induced reaction
      in cutinase, i.e., light-induced disruption of disulphide bridges mediated by the
      excitation of aromatic residues. Knowledge about the nature of the formed species
      and their lifetimes is important for the understanding of UV-induced reactions in
      humans that lead to light-induced diseases, e.g., skin cancer and cataract
      formation.

PMID- 19580760
TI  - Primary reactions of the LOV2 domain of phototropin studied with ultrafast mid
      infrared spectroscopy and quantum chemistry.
AB  - Phototropins, major blue-light receptors in plants, are sensitive to blue light
      through a pair of flavin mononucleotide (FMN)-binding light oxygen and voltage
      (LOV) domains, LOV1 and LOV2. LOV2 undergoes a photocycle involving light-driven
      covalent adduct formation between a conserved cysteine and the FMN C(4a) atom.
      Here, the primary reactions of Avena sativa phototropin 1 LOV2 (AsLOV2) were
      studied using ultrafast mid-infrared spectroscopy and quantum chemistry. The
      singlet excited state (S1) evolves into the triplet state (T1) with a lifetime of
      1.5 ns at a yield of approximately 50%. The infrared signature of S1 is
      characterized by absorption bands at 1657 cm(-1), 1495-1415 cm(-1), and 1375 cm(
      1). The T1 state shows infrared bands at 1657 cm(-1), 1645 cm(-1), 1491-1438 cm(
      1), and 1390 cm(-1). For both electronic states, these bands are assigned
      principally to C=O, C=N, C-C, and C-N stretch modes. The overall downshifting of
      C=O and C=N bond stretch modes is consistent with an overall bond-order decrease
      of the conjugated isoalloxazine system upon a pi-pi* transition. The
      configuration interaction singles (CIS) method was used to calculate the
      vibrational spectra of the S1 and T1 excited pipi* states, as well as respective
      electronic energies, structural parameters, electronic dipole moments, and
      intrinsic force constants. The harmonic frequencies of S1 and T1, as calculated
      by the CIS method, are in satisfactory agreement with the evident band positions
      and intensities. On the other hand, CIS calculations of a T1 cation that was
      protonated at the N(5) site did not reproduce the experimental FMN T1 spectrum.
      We conclude that the FMN T1 state remains nonprotonated on a nanosecond
      timescale, which rules out an ionic mechanism for covalent adduct formation
      involving cysteine-N(5) proton transfer on this timescale. Finally, we observed a
      heterogeneous population of singly and doubly H-bonded FMN C(4)=O conformers in
      the dark state, with stretch frequencies at 1714 cm(-1) and 1694 cm(-1),
      respectively.

PMID- 19580761
TI  - Conformational heterogeneity and propagation of structural changes in the
      LOV2/Jalpha domain from Avena sativa phototropin 1 as recorded by temperature
      dependent FTIR spectroscopy.
AB  - Phototropins control phototropism, chloroplast movement, stomatal opening, and
      leaf expansion in plants. Phototropin 1 (phot1) is composed of a kinase domain
      linked to two blue light-sensing domains, LOV2 and LOV1, which bind flavin
      mononucleotide. Disruption of the interaction between the LOV2 domain and a
      helical segment named Jalpha, joining LOV to the kinase domain, induces the
      subsequent kinase activity of phototropin 1 and further-downstream signal
      transduction. Here we study the effects of temperature and hydration on the light
      triggered signal propagation in the phot1 LOV2 domain of Avena sativa
      (AsLOV2/Jalpha), using Fourier transform infrared spectroscopy to unravel part of
      the molecular mechanism of phototropin 1. We report that AsLOV2/Jalpha shows an
      intense signal in the amide I and II regions, arising mainly from beta-sheet
      changes and the unbinding of the Jalpha helix from the Per-ARNT-Sim core and its
      subsequent partial unfolding. Importantly, these structural changes only occur
      under conditions of full hydration and at temperatures above 280 K. We
      characterized a newly isolated low-hydration intermediate that shows a downshift
      of high-frequency amide I signals and that possibly corresponds to loop
      tightening, without large beta-sheet or Jalpha structural changes. In addition,
      we report a heterogeneity in AsLOV2/Jalpha involving two different C(4)=O
      conformer populations, coexisting in the dark state and characterized by C(4)=O
      carbonyl frequencies at 1712 cm(-1) and 1694 cm(-1) that are attributable to a
      single H-bond and two H-bonds at this site, respectively. Such conformers display
      slightly shifted absorption spectra and cause a splitting of the 475-nm band in
      the ultraviolet/visible spectra of LOV domains at low temperature.

PMID- 19580762
TI  - Fatty acid transfer from Yarrowia lipolytica sterol carrier protein 2 to
      phospholipid membranes.
AB  - Sterol carrier protein 2 (SCP2) is an intracellular protein domain found in all
      forms of life. It was originally identified as a sterol transfer protein, but was
      recently shown to also bind phospholipids, fatty acids, and fatty-acyl-CoA with
      high affinity. Based on studies carried out in higher eukaryotes, it is believed
      that SCP2 targets its ligands to compartmentalized intracellular pools and
      participates in lipid traffic, signaling, and metabolism. However, the biological
      functions of SCP2 are incompletely characterized and may be different in
      microorganisms. Herein, we demonstrate the preferential localization of SCP2 of
      Yarrowia lipolytica (YLSCP2) in peroxisome-enriched fractions and examine the
      rate and mechanism of transfer of anthroyloxy fatty acid from YLSCP2 to a variety
      of phospholipid membranes using a fluorescence resonance energy transfer assay.
      The results show that fatty acids are transferred by a collision-mediated
      mechanism, and that negative charges on the membrane surface are important for
      establishing a "collisional complex". Phospholipids, which are major constituents
      of peroxisome and mitochondria, induce special effects on the rates of transfer.
      In conclusion, YLSCP2 may function as a fatty acid transporter with some degree
      of specificity, and probably diverts fatty acids to the peroxisomal metabolism.

PMID- 19580763
TI  - Ligand extraction properties of the GM2 activator protein and its interactions
      with lipid vesicles.
AB  - The GM2 activator protein (GM2AP) is an accessory protein required for the
      enzymatic conversion of GM2 to GM3 by hydrolases in the lysosomal compartments of
      cells. Here, GM2AP interactions with lipid vesicles are investigated by sucrose
      loaded vesicle sedimentation and gel filtration assays, and the effects of pH and
      lipid composition on membrane binding and lipid extraction are characterized. The
      sedimentation experiments allow for facile quantification of the percentage of
      protein in solution and on the bilayer surface, with detailed analysis of the
      protein:lipid complex that remains in solution. Optimum binding and ligand
      extraction is found for pH 4.8 where <15% of the protein remains surface
      associated regardless of the lipid composition. In addition to extracting GM2, we
      find that GM2AP readily extracts dansyl-headgroup-labeled lipids as well as other
      phospholipids from vesicles. The ability of GM2AP to extract dansyl-DHPE from
      vesicles is altered by pH and the specific ligand GM2. Although the unique
      endosomal lipid, bis(monoacylglycero)phosphate, is not required for ligand
      extraction, it does enhance the extraction efficiency of GM2 when cholesterol is
      present in the vesicles.

PMID- 19580765
TI  - Influence of residue 22 on the folding, aggregation profile, and toxicity of the
      Alzheimer's amyloid beta peptide.
AB  - Several biophysical techniques have been used to determine differences in the
      aggregation profile (i.e., the secondary structure, aggregation propensity,
      dynamics, and morphology of amyloid structures) and the effects on cell viability
      of three variants of the amyloid beta peptide involved in Alzheimer's disease. We
      focused our study on the Glu22 residue, comparing the effects of freshly prepared
      samples and samples aged for at least 20 days. In the aged samples, a high
      propensity for aggregation and beta-sheet secondary structure appears when
      residue 22 is capable of establishing polar (Glu22 in wild-type) or hydrophobic
      (Val22 in E22V) interactions. The Arctic variant (E22G) presents a mixture of
      mostly disordered and alpha-helix structures (with low beta-sheet contribution).
      Analysis of transmission electron micrographs and atomic force microscopy images
      of the peptide variants after aging showed significant quantitative and
      qualitative differences in the morphology of the formed aggregates. The effect on
      human neuroblastoma cells of these Abeta(12-28) variants does not correlate with
      the amount of beta-sheet of the aggregates. In samples allowed to age, the native
      sequence was found to have an insignificant effect on cell viability, whereas the
      Arctic variant (E22G), the E22V variant, and the slightly-aggregating control
      (F19G-F20G) had more prominent effects.

PMID- 19580764
TI  - Influence of the charge at D85 on the initial steps in the photocycle of
      bacteriorhodopsin.
AB  - Studies have shown that trans-cis isomerization of retinal is the primary
      photoreaction in the photocycle of the light-driven proton pump bacteriorhodopsin
      (BR) from Halobacterium salinarum, as well as in the photocycle of the chloride
      pump halorhodopsin (HR). The transmembrane proteins HR and BR show extensive
      structural similarities, but differ in the electrostatic surroundings of the
      retinal chromophore near the protonated Schiff base. Point mutation of BR of the
      negatively charged aspartate D85 to a threonine T (D85T) in combination with
      variation of the pH value and anion concentration is used to study the ultrafast
      photoisomerization of BR and HR for well-defined electrostatic surroundings of
      the retinal chromophore. Variations of the pH value and salt concentration allow
      a switch in the isomerization dynamics of the BR mutant D85T between BR-like and
      HR-like behaviors. At low salt concentrations or a high pH value (pH 8), the
      mutant D85T shows a biexponential initial reaction similar to that of HR. The
      combination of high salt concentration and a low pH value (pH 6) leads to a
      subpopulation of 25% of the mutant D85T whose stationary and dynamic absorption
      properties are similar to those of native BR. In this sample, the combination of
      low pH and high salt concentration reestablishes the electrostatic surroundings
      originally present in native BR, but only a minor fraction of the D85T molecules
      have the charge located exactly at the position required for the BR-like fast
      isomerization reaction. The results suggest that the electrostatics in the native
      BR protein is optimized by evolution. The accurate location of the fixed charge
      at the aspartate D85 near the Schiff base in BR is essential for the high
      efficiency of the primary reaction.

PMID- 19580766
TI  - Domain features of the peripheral stalk subunit H of the methanogenic A1AO ATP
      synthase and the NMR solution structure of H(1-47).
AB  - A series of truncated forms of subunit H were generated to establish the domain
      features of that protein. Circular dichroism analysis demonstrated that H is
      divided at least into a C-terminal coiled-coil domain within residues 54-104, and
      an N-terminal domain formed by adjacent alpha-helices. With a cysteine at the C
      terminus of each of the truncated proteins (H(1-47), H(1-54), H(1-59), H(1-61),
      H(1-67), H(1-69), H(1-71), H(1-78), H(1-80), H(1-91), and H(47-105)), the
      residues involved in formation of the coiled-coil interface were determined.
      Proteins H(1-54), H(1-61), H(1-69), and H(1-80) showed strong cross-link
      formation, which was weaker in H(1-47), H(1-59), H(1-71), and H(1-91). A shift in
      disulfide formation between cysteines at positions 71 and 80 reflected an
      interruption in the periodicity of hydrophobic residues in the region
      71AEKILEETEKE81. To understand how the N-terminal domain of H is formed, we
      determined for the first time, to our knowledge, the solution NMR structure of
      H(1-47), which revealed an alpha-helix between residues 15-42 and a flexible N
      terminal stretch. The alpha-helix includes a kink that would bring the two
      helices of the C-terminus into the coiled-coil arrangement. H(1-47) revealed a
      strip of alanines involved in dimerization, which were tested by exchange to
      single cysteines in subunit H mutants.

PMID- 19580767
TI  - Slowing down downhill folding: a three-probe study.
AB  - The mutant Tyr22Trp/Glu33Tyr/Gly46Ala/Gly48Ala of lambda repressor fragment
      lambda(6-85) was previously assigned as an incipient downhill folder. We slow
      down its folding in a cryogenic water-ethylene-glycol solvent (-18 to -28 degrees
      C). The refolding kinetics are probed by small-angle x-ray scattering, circular
      dichroism, and fluorescence to measure the radius of gyration, the average
      secondary structure content, and the native packing around the single tryptophan
      residue. The main resolved kinetic phase of the mutant is probe independent and
      faster than the main phase observed for the pseudo-wild-type. Excess helical
      structure formed early on by the mutant may reduce the formation of turns and
      prevent the formation of compact misfolded states, speeding up the overall
      folding process. Extrapolation of our main cryogenic folding phase and previous T
      jump measurements to 37 degrees C yields nearly the same refolding rate as
      extrapolated by Oas and co-workers from NMR line-shape data. Taken together, all
      the data consistently indicate a folding speed limit of approximately 4.5 micros
      for this fast folder.

PMID- 19580768
TI  - Thermodynamics of beta-sheet formation in polyglutamine.
AB  - The role of beta-sheets in the early stages of protein aggregation, specifically
      amyloid formation, remains unclear. Interpretations of kinetic data have led to a
      specific model for the role of beta-sheets in polyglutamine aggregation.
      According to this model, monomeric polyglutamine, which is intrinsically
      disordered, goes through a rare conversion into an ordered, metastable, beta
      sheeted state that nucleates aggregation. It has also been proposed that the
      probability of forming the critical nucleus, a specific beta-sheet conformation
      for the monomer, increases with increasing chain length. Here, we test this model
      using molecular simulations. We quantified free energy profiles in terms of beta
      content for monomeric polyglutamine as a function of chain length. In accord with
      estimates from experimental data, the free energy penalties for forming beta-rich
      states are in the 10-20 kcal/mol range. However, the length dependence of these
      free energy penalties does not mirror interpretations of kinetic data. In
      addition, although homodimerization of disordered molecules is spontaneous, the
      imposition of conformational restraints on polyglutamine molecules does not
      enhance the spontaneity of intermolecular associations. Our data lead to the
      proposal that beta-sheet formation is an attribute of peptide-rich phases such as
      high molecular weight aggregates rather than monomers or oligomers.

PMID- 19580769
TI  - Influence of the amino-acid sequence on the inverse temperature transition of
      elastin-like polymers.
AB  - This work explores the dependence of the inverse temperature transition of
      elastin-like polymers (ELPs) on the amino-acid sequence, i.e., the amino-acid
      arrangement along the macromolecule and the resulting linear distribution of the
      physical properties (mainly polarity) derived from it. The hypothesis of this
      work is that, in addition to mean polarity and molecular mass, the given amino
      acid sequence, or its equivalent--the way in which polarity is arranged along the
      molecule--is also relevant for determining the transition temperature and the
      latent heat of that transition. To test this hypothesis, a set of linear and di-
      and triblock ELP copolymers were designed and produced as recombinant proteins.
      The absolute sequence control provided by recombinant technologies allows the
      effect of the amino-acid arrangement to be isolated while keeping the molecular
      mass or mean polarity under strict control. The selected block copolymers were
      made of two different ELPs: one exhibiting temperature and pH responsiveness, and
      one exhibiting temperature responsiveness only. By changing the arrangement and
      length of the blocks while keeping other parameters, such as the molecular mass
      or mean polarity, constant, we were able to show that the sequence plays a key
      role in the smart behavior of ELPs.

PMID- 19580770
TI  - Protein-induced membrane curvature investigated through molecular dynamics
      flexible fitting.
AB  - In the photosynthetic purple bacterium Rhodobacter (Rba.) sphaeroides, light is
      absorbed by membrane-bound light-harvesting (LH) proteins LH1 and LH2. LH1
      directly surrounds the reaction center (RC) and, together with PufX, forms a
      dimeric (RC-LH1-PufX)2 protein complex. In LH2-deficient Rba. sphaeroides
      mutants, RC-LH1-PufX dimers aggregate into tubular vesicles with a radius of
      approximately 250-550 A, making RC-LH1-PufX one of the few integral membrane
      proteins known to actively induce membrane curvature. Recently, a three
      dimensional electron microscopy density map showed that the Rba. sphaeroides RC
      LH1-PufX dimer exhibits a prominent bend at its dimerizing interface. To
      investigate the curvature properties of this highly bent protein, we employed
      molecular dynamics simulations to fit an all-atom structural model of the RC-LH1
      PufX dimer within the electron microscopy density map. The simulations reveal how
      the dimer produces a membrane with high local curvature, even though the location
      of PufX cannot yet be determined uniquely. The resulting membrane curvature
      agrees well with the size of RC-LH1-PufX tubular vesicles, and demonstrates how
      the local curvature properties of the RC-LH1-PufX dimer propagate to form the
      observed long-range organization of the Rba. sphaeroides tubular vesicles.

PMID- 19580771
TI  - Multiscale measurements distinguish cellular and interstitial hindrances to
      diffusion in vivo.
AB  - Molecular cancer therapy relies on interstitial diffusion for drug distribution
      in solid tumors. A mechanistic understanding of how tumor components affect
      diffusion is necessary to advance cancer drug development. Yet, because of
      limitations in current techniques, it is unclear how individual tissue components
      hinder diffusion. We developed multiscale fluorescence recovery after
      photobleaching (MS-FRAP) to address this deficiency. Diffusion measurements
      facilitated by MS-FRAP distinguish the diffusive hindrance of the interstitial
      versus cellular constituents in living tissue. Using multiscale diffusion
      measurements in vivo, we resolved the contributions of these two major tissue
      components toward impeding diffusive transport in solid tumors and subcutaneous
      tissue in mice. We further used MS-FRAP in interstitial matrix-mimetic gels and
      in vivo to show the influence of physical interactions between collagen and
      hyaluronan on diffusive hindrance through the interstitium. Through these
      studies, we show that interstitial hyaluronan paradoxically improves diffusion
      and that reducing cellularity enhances diffusive macromolecular transport in
      solid tumors.

PMID- 19580772
TI  - Direct measurement of association and dissociation rates of DNA binding in live
      cells by fluorescence correlation spectroscopy.
AB  - Measurement of live-cell binding interactions is vital for understanding the
      biochemical reactions that drive cellular processes. Here, we develop,
      characterize, and apply a new procedure to extract information about binding to
      an immobile substrate from fluorescence correlation spectroscopy (FCS)
      autocorrelation data. We show that existing methods for analyzing such data by
      two-component diffusion fits can produce inaccurate estimates of diffusion
      constants and bound fractions, or even fail altogether to fit FCS binding data.
      By analyzing live-cell FCS measurements, we show that our new model can
      satisfactorily account for the binding interactions introduced by attaching a DNA
      binding domain to the dimerization domain derived from a site-specific
      transcription factor (the vitellogenin binding protein (VBP)). We find that our
      FCS estimates are quantitatively consistent with our fluorescence recovery after
      photobleaching (FRAP) measurements on the same VBP domains. However, due to the
      fast binding interactions introduced by the DNA binding domain, FCS generates
      independent estimates for the diffusion constant (6.7 +/- 2.4 microm2/s) and the
      association (2 +/- 1.2 s(-1)) and dissociation (19 +/- 7 s(-1)) rates, whereas
      FRAP produces only a single, but a consistent, estimate, the effective-diffusion
      constant (4.4 +/- 1.4 microm2/s), which depends on all three parameters. We apply
      this new FCS method to evaluate the efficacy of a potential anticancer drug that
      inhibits DNA binding of VBP in vitro and find that in vivo the drug inhibits DNA
      binding in only a subset of cells. In sum, we provide a straightforward approach
      to directly measure binding rates from FCS data.

PMID- 19580773
TI  - Evidence that mechanosensors with distinct biomechanical properties allow for
      specificity in mechanotransduction.
AB  - Various cell types can sense and convert mechanical forces into biochemical
      signaling events through a process called mechanotransduction, and this process
      is often highly specific to the types of mechanical forces applied. However, the
      mechanism(s) that allow for specificity in mechanotransduction remain undefined.
      Thus, the goal of this study was to gain insight into how cells distinguish among
      specific types of mechanical information. To accomplish this goal, we determined
      if skeletal myoblasts can distinguish among differences in strain, strain rate,
      and strain-time integral (STI). Our results demonstrate that mechanically induced
      signaling through the c-jun N-terminal kinase 2 [JNK2] is elicited via a
      mechanism that depends on an interaction between the magnitude of strain and
      strain rate and is independent of STI. In contrast to JNK2, mechanically induced
      signaling through the ribosomal S6 kinase [p70(389)] is not strain rate
      sensitive, but instead involves a magnitude of strain and STI dependent
      mechanisms. Mathematical modeling also indicated that mechanically induced
      signaling through JNK2 and p70(389) can be isolated to separate viscous and
      elastic mechanosensory elements, respectively. Based on these results, we propose
      that skeletal myoblasts contain multiple mechanosensory elements with distinct
      biomechanical properties and that these distinct biomechanical properties provide
      a mechanism for specificity in mechanotransduction.

PMID- 19580774
TI  - Substrate topography induces a crossover from 2D to 3D behavior in fibroblast
      migration.
AB  - In a three-dimensional environment, cells migrate through complex topographical
      features. Using microstructured substrates, we investigate the role of substrate
      topography in cell adhesion and migration. To do so, fibroblasts are plated on
      chemically identical substrates composed of microfabricated pillars. When the
      dimensions of the pillars (i.e., the diameter, length, and spacing) are varied,
      migrating cells encounter alternating flat and rough surfaces that depend on the
      spacing between the pillars. Consequently, we show that substrate topography
      affects cell shape and migration by modifying cell-to-substrate interactions.
      Cells on micropillar substrates exhibit more elongated and branched shapes with
      fewer actin stress fibers compared with cells on flat surfaces. By analyzing the
      migration paths in various environments, we observe different mechanisms of cell
      migration, including a persistent type of migration, that depend on the
      organization of the topographical features. These responses can be attributed to
      a spatial reorganization of the actin cytoskeleton due to physical constraints
      and a preferential formation of focal adhesions on the micropillars, with an
      increased lifetime compared to that observed on flat surfaces. By changing myosin
      II activity, we show that actomyosin contractility is essential in the cellular
      response to micron-scale topographic signals. Finally, the analysis of cell
      movements at the frontier between flat and micropillar substrates shows that cell
      transmigration through the micropillar substrates depends on the spacing between
      the pillars.

PMID- 19580775
TI  - Molecular accessibility in relation to cell surface topography and compression
      against a flat substrate.
AB  - The recruitment of cells to the vascular wall in vivo or the capture of cell
      subpopulations at the surface of a fabricated device requires the formation of
      bonds between specific molecular pairs on the cell and the substrate. The ability
      of a molecule to form a bond depends critically on its localization relative to
      the cell surface topography. In this report, we present a framework for the
      quantitative assessment of molecular availability that accounts for the
      deformability of the cell surface and the balance of forces in the interface, as
      well as the variability of surface protrusion lengths and the preference for
      molecules to reside at or away from the tips of surface projections. We also
      examined how molecular availability should change with increasing compression of
      the cell against the substrate. Finally, we convolved the distribution of
      molecules at the interface with a decaying evanescent excitation to predict the
      fluorescence intensity in total internal reflectance fluorescence microscopy,
      which can provide a quantitative measure of the relative availability of
      different molecules at a cell-substrate interface. Model predictions show good
      agreement with measurements of fluorescence intensity of different molecules
      labeled fluorescently on the surface of a human neutrophil compressed against a
      glass surface.

PMID- 19580776
TI  - Cell adhesion molecule distribution relative to neutrophil surface topography
      assessed by TIRFM.
AB  - The positioning of adhesion molecules relative to the microtopography of the cell
      surface has a significant influence on the molecule's availability to form
      adhesive contacts. Measurements of the ratio of fluorescence intensity per unit
      area in epi-fluorescence images versus total internal reflection fluorescence
      images provides a means to assess the relative accessibility for bond formation
      of different fluorescently labeled molecules in cells pressed against a flat
      substrate. Measurements of the four principal adhesion molecules on human
      neutrophils reveal that L-selectin has the highest ratio of total internal
      reflection fluorescence/epi intensity, and that P-selectin glycoprotein ligand-1
      (PSGL-1) and the integrins alphaLbeta2 (LFA-1) and alphaMbeta2 (Mac-1) have
      ratios similar to each other but lower than for L-selectin. All of the ratios
      increased with increasing impingement, indicating an alteration of surface
      topography with increasing surface compression. These results are consistent with
      model predictions for molecules concentrated near the tips of microvilli in the
      case of L-selectin, and sequestered away from the microvillus tips in the case of
      LFA-1, Mac-1, and PSGL-1. The results confirm differences among adhesion
      molecules in their surface distribution and reveal how the availability of
      specific adhesion molecules is altered by mechanical compression of the surface
      in live cells.

PMID- 19580778
TI  - The functional expression of toxic genes: lessons learned from molecular cloning
      of CCH1, a high-affinity Ca2+ channel.
AB  - Some genes cannot be cloned by conventional methods because in most cases the
      genes or gene products are toxic to Escherichia coli. CCH1 is a high-affinity
      Ca(2+) channel present in the plasma membrane of Cryptococcus neoformans and
      other fungi. Like many toxic genes, the molecular cloning of CCH1 has been a
      major challenge; consequently, direct studies of CCH1 channel activity in
      heterologous expression systems have been impossible. We have devised a
      straightforward approach that resulted in the molecular cloning and functional
      expression of CCH1 by exploiting homologous recombination both in vitro and in
      vivo. This approach precluded the standard enzyme digestion-mediated ligation
      reactions and the subsequent isolation of plasmids from E. coli. The shuttle
      plasmid carrying CCH1-GFP, which was prepared in vitro and propagated in yeast,
      was successfully expressed in the mammalian cell line HEK293 (human embryonic
      kidney 293). CCH1 transcripts were detected only in HEK293 cells transfected with
      the plasmid DNA. Fluorescence microscopy studies revealed the expression of CCH1
      GFP fusion protein on the cell surface of HEK293 cells, similar to the
      localization pattern of a well-characterized plasma membrane-associated K(+)
      channel. This approach will be particularly useful for genes that encode ion
      channels and transporters that cannot be cloned by conventional techniques
      requiring E. coli.

PMID- 19580777
TI  - Measuring ion channels on solid supported membranes.
AB  - Application of solid supported membranes (SSMs) for the functional investigation
      of ion channels is presented. SSM-based electrophysiology, which has been
      introduced previously for the investigation of active transport systems, is
      expanded for the analysis of ion channels. Membranes or liposomes containing ion
      channels are adsorbed to an SSM and a concentration gradient of a permeant ion is
      applied. Transient currents representing ion channel transport activity are
      recorded via capacitive coupling. We demonstrate the application of the technique
      to liposomes reconstituted with the peptide cation channel gramicidin, vesicles
      from native tissue containing the nicotinic acetylcholine receptor, and membranes
      from a recombinant cell line expressing the ionotropic P2X2 receptor. It is shown
      that stable ion gradients, both inside as well as outside directed, can be
      applied and currents are recorded with an excellent signal/noise ratio. For the
      nicotinic acetylcholine receptor and the P2X2 receptor excellent assay quality
      factors of Z' = 0.55 and Z' = 0.67, respectively, are obtained. This technique
      opens up new possibilities in cases where conventional electrophysiology fails
      like the functional characterization of ion channels from intracellular
      compartments. It also allows for robust fully automatic assays for drug
      screening.

PMID- 19580779
TI  - Multiple roles of the active site lysine of Dopa decarboxylase.
AB  - The pyridoxal 5'-phosphate dependent-enzyme Dopa decarboxylase, responsible for
      the irreversible conversion of l-Dopa to dopamine, is an attractive drug target.
      The contribution of the pyridoxal-Lys303 to the catalytic mechanisms of
      decarboxylation and oxidative deamination is analyzed. The K303A variant binds
      the coenzyme with a 100-fold decreased apparent equilibrium binding affinity with
      respect to the wild-type enzyme. Unlike the wild-type, K303A in the presence of l
      Dopa displays a parallel progress course of formation of both dopamine and 3,4
      dihydroxyphenylacetaldehyde (plus ammonia) with a burst followed by a linear
      phase. Moreover, the finding that the catalytic efficiencies of decarboxylation
      and of oxidative deamination display a decrease of 1500- and 17-fold,
      respectively, with respect to the wild-type, is indicative of a different impact
      of Lys303 mutation on these reactions. Kinetic analyses reveal that Lys303 is
      involved in external aldimine formation and hydrolysis as well as in product
      release which affects the rate-determining step of decarboxylation.

PMID- 19580780
TI  - Dissection of Rab7 localization on Mycobacterium tuberculosis phagosome.
AB  - The late endosomal marker Rab7 has been long believed to be absent from the
      phagosome containing Mycobacterium tuberculosis (M.tb) in macrophage, but the
      detail kinetics remains elusive. Here, we found that Rab7 is transiently
      recruited to and subsequently released from M.tb phagosomes. For further
      understanding of the effect of Rab7 dissociation from the phagosome, we examined
      the localization of lysosomal markers on the phagosome in the macrophage
      expressing a dominant-negative Rab7. The localization of lysosomal associated
      membrane protein-2 (LAMP-2) on the phagosome was Rab7-independent, while that of
      cathepsin D was Rab7-dependent. These results agree with the localization of each
      lysosomal marker on M.tb phagosome at 6h postinfection-i.e., LAMP-2, but not
      cathepsin D localized on the majority of M.tb phagosomes. These results suggest
      that the dissociation of Rab7 from M.tb phagosome is the important process in
      inhibition of phagolysosome biogenesis.

PMID- 19580781
TI  - Controlling aggregation propensity in A53T mutant of alpha-synuclein causing
      Parkinson's disease.
AB  - Understanding alpha-synuclein in terms of fibrillization, aggregation, solubility
      and stability is fundamental in Parkinson's disease (PD). The three familial
      mutations, namely, A30P, E46K and A53T cause PD because the hydrophobic regions
      in alpha-synuclein acquire beta-sheet configuration, and have a propensity to
      fibrillize and form amyloids that cause cytotoxicity and neurodegeneration. On
      simulating the native form and mutants (A30P, E46K and A53T) of alpha-synuclein
      in water solvent, clear deviations are observed in comparison to the all-helical
      1XQ8 PDB structure. We have identified two crucial residues, (40)Val and (74)Val,
      which play key roles in beta-sheet aggregation in the hydrophobic regions 36-41
      and 68-78, respectively, leading to fibrillization and amyloidosis in familial
      (A53T) PD. We have also identified V40D_V74D, a double mutant of A53T (the most
      amyloidogenic mutant). The simultaneous introduction of these two mutations in
      A53T nearly ends its aggregation propensity, increases its solubility and
      positively enhances its thermodynamic stability.

PMID- 19580783
TI  - Cellular protein TTRAP interacts with HIV-1 integrase to facilitate viral
      integration.
AB  - TTRAP is a PML-NB protein that is involved in the NF-kappaB signaling pathway.
      TTRAP was recently identified by yeast two-hybrid analysis as a HIV-1 integrase
      (HIV-1 IN) interacting protein. This interaction was verified by co
      immunoprecipitation, GST pull-down, and intracellular imaging, and deletion
      assays suggested that the N-terminal 180 residues of TTRAP are responsible for
      the interaction. In stable TTRAP knock-down cell lines, the integration of viral
      vectors decreased significantly compared with non-silenced cell lines.
      Conversely, overexpression of TTRAP by transient transfection increased the
      percentage of integration events. This is the first time that TTRAP has been
      shown to interact with HIV-1 IN and facilitate lentiviral vector integration.
      These findings reveal a new function of TTRAP and expand our understanding of the
      cellular response to HIV infection. The interaction between TTRAP and HIV-1 IN
      may be useful in designing new anti-viral strategies as well as for improving the
      efficiency of lentiviral-vector-mediated gene delivery.

PMID- 19580784
TI  - Calreticulin enhances B2 bradykinin receptor maturation and heterodimerization.
AB  - In different native tissues and cells the receptor for the vasodepressor
      bradykinin, B(2), forms dimers with the receptor for the vasopressor angiotensin
      II, AT(1). Because AT(1)/B(2) heterodimers may contribute to enhanced angiotensin
      II-stimulated signaling under pathophysiological conditions, we analyzed
      mechanisms of AT(1)/B(2) heterodimerization. We found that efficient B(2)
      receptor maturation was a prerequisite for heterodimerization because only the
      fully mature B(2) receptor was capable to interact with AT(1). To identify
      chaperones involved in B(2) receptor maturation and heterodimerization we
      performed microarray gene expression profiling of human embryonic kidney (HEK293)
      cells. The expression of the chaperone calreticulin was up-regulated in cells
      with efficient B(2) receptor maturation. Vice versa, upon down regulation of
      calreticulin expression by RNA interference, B(2) receptor maturation and
      AT(1)/B(2) receptor heterodimerization were significantly impaired.
      Concomitantly, the B(2) receptor-mediated enhancement of AT(1)-stimulated
      signaling was reduced. Thus, calreticulin enhances B(2) receptor maturation and
      heterodimerization with AT(1).

PMID- 19580782
TI  - Differential regulation of neuronal and inducible nitric oxide synthase (NOS) in
      the spinal cord of mutant SOD1 (G93A) ALS mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder
      characterized by degeneration of motor neurons throughout the central nervous
      system. Mutations of the free radical scavenging enzyme superoxide dismutase-1
      (SOD1) are a cause of familial ALS but it is not known how mutations lead to cell
      death. Free radicals such as nitric oxide (NO) are thought to play a key
      pathogenic role. NO is synthesized by NO synthases (NOSs) from arginine, which is
      a rate-limiting factor for NO production. We found that neuronal NOS (nNOS)
      positive motor neurons were depleted while inducible NOS (iNOS)-positive
      activated glial cells were increased in transgenic mtSOD1 (G93A) ALS mice. iNOS
      expression was up regulated consistent with the increases of motor neuron loss
      and glial activation and citrulline and NO levels while nNOS expression was
      decreased in G93A ALS mice. Administration of l-arginine to G93A mice reduced the
      severity of motor neuron depletion and glial activation. In treated animals, nNOS
      expression was preserved while citrulline and NO were reduced, possibly due to
      reduced activation of glia expressing iNOS. Our findings show that high
      concentrations of NO correlate with iNOS expression rather than nNOS expression
      in G93A ALS mice. This suggests that therapy focused on iNOS inhibition might be
      a fruitful direction for future ALS therapeutic trials.

PMID- 19580786
TI  - Gangliosides are involved in neural differentiation of human dental pulp-derived
      stem cells.
AB  - Human dental pulp-derived stem cells (hDPSCs) have been considered alternative
      sources of adult stem cells because of their potential to differentiate into
      multiple cell lineages. This study investigated the possible role of gangliosides
      in the neural differentiation of hDPSCs. When hDPSCs were cultured under neural
      differentiation conditions, expression of neural cell marker genes such as
      Nestin, MAP-2, and NeuN was detected. Immunostaining and high-performance thin
      layer chromatography analysis showed that an increase in ganglioside biosynthesis
      was associated with neural differentiation of hDPSCs. Specifically, a significant
      increase in GD3 and GD1a expression was observed during neural differentiation.
      To confirm the role of gangliosides in neural differentiation, ganglioside
      biosynthesis was inhibited in hDPSCs by knockdown of UDP-glucose ceramide
      glucosyltransferase (Ugcg), which prevented differentiation into neural cells.
      These results suggest that gangliosides may play a role in the neural
      differentiation process of hDPSCs.

PMID- 19580785
TI  - Increased extracellular pressure provides a novel adjuvant stimulus for
      enhancement of conventional dendritic cell maturation strategies.
AB  - Dendritic cell (DC)-based vaccine strategies have gained increasing popularity in
      recent years. Methods for ex vivo generation of immunocompetent mature DCs still
      require optimization. DCs have been shown to phenotypically mature under elevated
      pressure. We compared the effects of pressure on DC maturation with LPS- and
      cytokine-stimulation. Human monocyte-derived immature or LPS- and cytokine
      matured DCs were exposed to ambient or 40 mmHg increased pressure for 12h, then
      assessed for expression of CD80, CD86, CD40, MHC-I/II, and inflammatory cytokine
      production. DCs were also evaluated for capacity to stimulate T-cell
      proliferation by co-culture with allogeneic lymphocytes. Pressure significantly
      increased cytokine production and expression of all surface molecules on immature
      DC other than MHC-I and CD40. Pressure/LPS-treated DCs displayed further
      upregulation of MHC-I, CD40, and IL-12p70. Cytokine-matured DCs appeared less
      responsive to pressure. T-cell proliferation correlated with MHC expression.
      Results suggest mechanical stimulation of DCs may provide a useful adjuvant to
      TLR-agonist maturation strategies.

PMID- 19580787
TI  - Tyrosine phosphorylation of vinexin in v-Src-transformed cells attenuates the
      affinity for vinculin.
AB  - Vinexin is an adaptor-type focal adhesion protein that interacts with vinculin.
      Here, we report the tyrosine phosphorylation of vinexin alpha in v-Src
      transformed NIH3T3 cells. Point mutational analysis of vinexin alpha clarified
      that three tyrosine residues in vinexin alpha were phosphorylated. A non
      phosphorylatable mutant of vinexin alpha had higher binding affinity for vinculin
      than its wild-type counterpart. In conclusion, vinexin alpha is tyrosine
      phosphorylated in v-Src-transformed cells, and this tyrosine phosphorylation of
      vinexin alpha attenuates the association of vinexin alpha with vinculin.

PMID- 19580788
TI  - Small interfering RNA targeting CD81 ameliorated arthritis in rats.
AB  - CD81 belongs to a family of cell-surface protein (tetraspanin) known as one of
      the up-regulated elements in rheumatoid arthritis synoviocytes. In this study,
      the therapeutic effect of small interfering RNA targeting CD81 (siCD81) was
      examined by in vivo electroporation method. Treatment with siCD81 significantly
      ameliorated paw swelling of collagen-induced arthritic (CIA) rats. In
      histological examination, hypertrophy of synovium, bone erosion, and degeneration
      of articular cartilage were milder in rats treated with siCD81 than in the
      control group and the non-specific siRNA group. Expression of synoviolin, a
      rheumatoid regulator, was suppressed by siCD81. Thus, therapeutic intervention by
      targeting CD81 may be used in the treatment of rheumatoid arthritis.

PMID- 19580789
TI  - Broad neutralizing human monoclonal antibodies against influenza virus from
      vaccinated healthy donors.
AB  - Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections
      could provide information on human epitopes important for the development of
      vaccines as well as potential therapeutic applications. Through the fusion of
      peripheral blood mononuclear cells from a total of five influenza-vaccinated
      volunteers, with newly developed murine-human chimera fusion partner cells, named
      SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus
      antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for
      influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within
      subtype and four (two for H3N2 and two for B) showed broad neutralizing ability.
      Importantly, epitope mapping revealed that the two broad neutralizing antibodies
      to H3N2 derived from different donors recognized the same epitope located
      underneath the receptor-binding site of the hemagglutinin globular region that is
      highly conserved among H3N2 strains.

PMID- 19580790
TI  - Pharmacological characterization of a selective agonist for bombesin receptor
      subtype-3.
AB  - Bombesin receptor subtype-3 (BRS-3) is an orphan G protein-coupled receptor in
      the bombesin receptor family that still awaits identification of its natural
      ligand. BRS-3 deficient mice develop a mild late-onset obesity with metabolic
      defects, implicating BRS-3 plays a role in feeding and metabolism. We describe
      here the pharmacological characterization of a synthetic compound, 16a, which
      serves as a potent agonist for BRS-3. This compound is selective for BRS-3 as it
      does not activate neuromedin B or gastrin-releasing peptide receptors, two most
      closely related bombesin receptors, as well as a series of other GPCRs. We
      assessed the receptor trafficking of BRS-3 and found that compound 16a promoted
      beta-arrestin translocation to the cell membrane. Neither central nor peripheral
      administration of compound 16a affects locomotor activity in mice. Therefore
      compound 16a is a potential tool to study the function of the BRS-3 system in
      vitro and possibly in vivo.

PMID- 19580791
TI  - Curcumin derivatives: molecular basis of their anti-cancer activity.
AB  - Curcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide
      spectrum of chemopreventive, antioxidant and antitumor properties. Although its
      promising chemotherapeutic activity, preclinical and clinical studies highlight
      Curcumin limited therapeutic application due to its instability in physiological
      conditions. To improve its stability and activity, many derivatives have been
      synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and
      diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more
      stable than Curcumin in physiological medium. To explore the mechanism of their
      chemotherapeutic effect, we studied their role in proliferation in the HCT116
      human colon cancer cells. We correlated kinetic stability and cellular uptake
      data to their biological effects. Both bDMC and DAC impair correct spindles
      formation and induce a p53- and p21(CIP1/WAF1)-independent mitotic arrest, which
      is more stable and long-lasting for bDMC. A subsequent p53/p21(CIP1/WAF1)
      dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a
      consequence of the mitotic slippage, preventing post-mitotic cells from re
      entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct
      effect of the drug and concomitant to the mitotic block. Finally, we demonstrate
      that bDMC induces rapid DNA double-strand breaks, moving for its possible
      development in anti-cancer clinical applications.

PMID- 19580792
TI  - Dissociation of auditory and visual straight ahead in hemianopia.
AB  - The perception of body orientation in space can be significantly affected by
      unilateral brain damage. One syndrome associated with such a disorder is
      homonymous hemianopia, resulting from lesions in postchiasmatic afferent visual
      pathways. Several studies in patients with hemianopia have shown that their
      subjective straight ahead is shifted to the anopic (contralesional) side.
      However, subjective straight ahead was mostly measured with reference to visual
      stimuli. As visual space perception is known to be distorted in hemianopia, it
      thus remained unclear whether the previous findings reflected this unisensory
      deficit or a genuine abnormality of subjective body orientation in multisensory
      space. In the present study, the auditory and visual straight ahead directions
      were assessed in twelve patients with persistent pure hemianopia (without
      neglect) by using related adjustment methods. As in previous studies, the visual
      straight ahead was found to be significantly shifted toward the anopic side. By
      contrast, the patients' auditory straight ahead was approximately veridical, as
      in healthy controls. These results indicate that in hemianopia the subjective
      straight ahead, in its genuine sense as the perceived orientation of the body
      median sagittal plane in frontal multisensory space, is unaffected. This suggests
      that visual brain areas, as are damaged in hemianopia, are not directly involved
      in relating body position to the external space. With respect to therapies for
      rehabilitation of hemianopia, these findings may support recent approaches, in
      which visual stimuli are combined with auditory stimuli in order to improve
      visual search behaviour.

PMID- 19580793
TI  - Interaction of a bacterial dirhamnolipid with phosphatidylcholine membranes: a
      biophysical study.
AB  - FTIR spectroscopy and fluorescence polarization were used to show that a
      bacterial dirhamnolipid interacts with phospholipid membranes composed of DPPC,
      altering both the acyl chain and the interfacial region of the bilayer.
      Incorporation of increasing amounts of dirhamnolipid into (2)H-DPPC membranes
      broadened the transition and shifted the transition temperature toward lower
      values, according to the effect on the CD(2) stretching vibration. Examination of
      the (13)C=O stretching band of (13)C-DPPC indicated that, both below and above
      the phase transition, dirhamnolipid produced a shift of the band frequency toward
      higher values, indicating a strong dehydration of the phospholipid C=O groups,
      and therefore of the interfacial region of the membrane. The effects on DPH and
      TMA-DPH fluorescence polarization provided additional support to hypothesize on
      the location of trehalose lipid within the bilayer. The results shown here could
      help to explain some of the interesting membrane-related biological actions of
      rhamnolipids reported before.

PMID- 19580794
TI  - Hydrophilic carotenoids: facile syntheses of carotenoid oxime hydrochlorides as
      long-chain, highly unsaturated cationic (bola)amphiphiles.
AB  - Stable cationic carotenoid aggregates - predominantly of the J-type - develop
      when the hydrochlorides of carotenoid aldoximes and ketoximes are exposed to
      water. The oxime hydrochlorides are obtained by simple syntheses from
      commercially available food color carotenoids. Bluish-purple, unstable transient
      compounds were observed during hydrochlorination performed at liquid nitrogen
      temperature.

PMID- 19580795
TI  - High-dose penicillin G-treatment causes underestimation of serum albumin measured
      by a modified BCP method.

PMID- 19580796
TI  - Interference on the laboratory measurement of bilirubin: the effect of in vitro
      interactions.

PMID- 19580797
TI  - Serum IgG4 concentrations and IgG4-related sclerosing disease.
AB  - BACKGROUND: Based on histological and immunohistochemical examinations of various
      organs of patients with autoimmune pancreatitis (AIP), a new clinicopathological
      entity, IgG4-related systemic disease, was proposed. This study aimed to clarify
      clinical utility of serum IgG4 levels in differentiating AIP from other
      pancreatobiliary diseases, clinical utility of serum IgG4 levels in
      differentiating Mikulicz's disease from other salivary gland disorders, as well
      as in identifying other IgG4-related diseases. METHODS: Serum IgG4 levels were
      measured in 468 patients. RESULTS: The median serum IgG4 level was significantly
      greater in AIP (301.5mg/dl) than in other pancreatobiliary diseases (p<0.01).
      Using the cutoff value of 119 mg/dl that was determined on the basis of this
      study's ROC curve data, the sensitivity and specificity to distinguish AIP from
      pancreatic cancer were 82.1% and 94.8%, respectively. The median serum IgG4 level
      was significantly greater in Mikulicz's disease (357.0mg/dl) than in other
      salivary gland diseases (p<0.01). Of 75 patients with elevated serum IgG4 levels,
      15 had diseases other than pancreatobiliary and salivary gland diseases.
      CONCLUSIONS: Serum IgG4 levels were useful for diagnosing AIP and Mikulicz's
      disease. Some diseases with serum IgG4 level elevations may be lesions of IgG4
      related systemic disease without manifestations of AIP and Mikulicz's disease.

PMID- 19580798
TI  - The relevance of hemoglobin F measurement in the diagnosis of thalassemias and
      related hemoglobinopathies.
AB  - OBJECTIVES: The increase in hemoglobin (Hb) F level is variably associated to the
      presence of beta thalassemia trait, and is more typical in presence of deltabeta
      thalassemia and of hereditary persistence of fetal hemoglobin. In normal healthy
      subjects variable levels of HbF are related to the presence of the polymorphism
      (G)gamma -158 (C>T). Moreover, HbF can also be variably increased in association
      with other acquired conditions. The objective of this work is to review the role
      of the determination of HbF in various conditions. DESIGN AND METHODS: In the
      present document we comment on the need for accuracy and standardization, and on
      the interpretation of the HbF value, reviewing most crucial aspects related to
      this test. RESULTS: We present a practical flow-chart summarizing the
      significance of the HbF estimation in different thalassemia syndromes and related
      hemoglobinopathies. CONCLUSION: The determination of HbF is relevant for the
      final diagnosis of various physiopathological conditions. In our opinion its
      importance will increase in the following years, because of the proliferation of
      novel approaches for the induction of HbF synthesis as a cure for thalassemia
      syndromes.

PMID- 19580799
TI  - Hemoglobin disorders and endothelial cell interactions.
AB  - Endothelial damage and inflammation make a significant contribution to the
      pathophysiology of sickle cell disease (SCD) and the beta-thalassemia syndromes.
      Endothelial dysfunction and ensuing vasculopathy are implicated in pulmonary
      hypertension in the hemoglobinopathies and endothelial activation and endothelial
      blood cell adhesion, accompanied by inflammatory processes and oxidative stress,
      are imperative to the vaso-occlusive process in SCD. Herein, we discuss the role
      that the endothelium plays in all of these processes and the effect that genetic
      modifiers and hydroxyurea therapy may have upon endothelial interactions.
      Therapies targeting the endothelium and endothelial interactions may represent a
      promising approach for treating these diseases.

PMID- 19580800
TI  - Late extraembryonic morphogenesis and its zen(RNAi)-induced failure in the
      milkweed bug Oncopeltus fasciatus.
AB  - Many insects undergo katatrepsis, essential reorganization by the extraembryonic
      membranes that repositions the embryo. Knockdown of the zen gene by RNA
      interference (RNAi) prevents katatrepsis in the milkweed bug Oncopeltus
      fasciatus. However, the precise morphogenetic defect has been uncertain, and
      katatrepsis itself has not been characterized in detail. The dynamics of wild
      type and zen(RNAi) eggs were analyzed from time-lapse movies, supplemented by
      analysis of fixed specimens. These investigations identify three zen(RNAi)
      defects. First, a reduced degree of tissue contraction implies a role for zen in
      baseline compression prior to katatrepsis. Subsequently, a characteristic
      'bouncing' activity commences, leading to the initiation of katatrepsis in wild
      type eggs. The second zen(RNAi) defect is a delay in this activity, suggesting
      that a temporal window of opportunity is missed after zen knockdown. Ultimately,
      the extraembryonic membranes fail to rupture in zen(RNAi) eggs: the third defect.
      Nevertheless, the outer serosal membrane manages to contract, albeit in an
      aberrant fashion with additional phenotypic consequences for the embryo. These
      data identify a novel epithelial morphogenetic event - rupture of the 'serosal
      window' structure - as the ultimate site of defect. Overall, Oncopeltus zen seems
      to have a role in coordinating a number of pre-katatreptic events during mid
      embryogenesis.

PMID- 19580801
TI  - Smad2/3 activities are required for induction and patterning of the neuroectoderm
      in zebrafish.
AB  - Smad2 and Smad3, two essential nuclear effectors of transforming growth factor
      (Tgf)-beta signals, have been found to be implicated in mesoderm and endoderm
      development in vertebrate embryos. However, their roles in the induction and
      patterning of the neuroectoderm are not well established. In this study, we show
      that interference with Smad2/3 activities in zebrafish embryos, by injecting
      dnsmad3b mRNA encoding a dominant negative Smad3b mutant, inhibits the expression
      of the early neural markers sox2 and sox3 at the onset of gastrulation and
      results in reduction of the anterior neuroectodermal marker otx2 as well as the
      posterior neuroectodermal marker hoxb1b during late gastrulation, suggesting a
      role of Smad2/3 activities in neural induction. Conversely, excess Smad2/3
      activities, caused by injecting smad3b mRNA, lead to an enhancement of sox2 and
      sox3 expression in the ventral domains but an inhibition of their expression in
      the dorsalmost region at early stages. Overexpression of smad3b also causes
      ventral expansion of the otx2 and hoxb1b expression domains accompanied with
      rostral shift of the hoxb1b domain at late gastrulation stages. Collectively,
      these data indicate that Smad2/3 activities are required for neural induction and
      neuroectodermal posteriorization in zebrafish. Knockdown of chordin partially
      inhibits effect of smad3b overexpression on neural induction, implying that
      Smad2/3 exert their effect on neural induction in part by regulating the
      expression of Bmp antagonists. Furthermore, down-regulation or up-regulation of
      Smad2/3 activities in MZoep mutant embryos, which lack the organizer and
      mesendodermal tissues due to deficiency of Nodal signaling, still affects
      induction and patterning of the neuroectoderm, suggesting that Smad2/3 activities
      are implicated in neural development in the absence of the organizer and
      mesendodermal tissues. We additionally demonstrate that Smad2/3 activities
      cooperate with Wnt and Fgf signals in neural development. Thus, Smad2/3
      activities play important roles not only in mesendodermal development but also in
      neural development during early vertebrate embryogenesis.

PMID- 19580803
TI  - The nuclear receptor E75A has a novel pair-rule-like function in patterning the
      milkweed bug, Oncopeltus fasciatus.
AB  - Genetic studies of the fruit fly Drosophila have revealed a hierarchy of
      segmentation genes (maternal, gap, pair-rule and HOX) that subdivide the
      syncytial blastoderm into sequentially finer-scale coordinates. Within this
      hierarchy, the pair-rule genes translate gradients of information into periodic
      stripes of expression. How pair-rule genes function during the progressive mode
      of segmentation seen in short and intermediate-germ insects is an ongoing
      question. Here we report that the nuclear receptor Of'E75A is expressed with
      double segment periodicity in the head and thorax. In the abdomen, Of'E75A is
      expressed in a unique pattern during posterior elongation, and briefly resembles
      a sequence that is typical of pair-rule genes. Depletion of Of'E75A mRNA caused
      loss of a subset of odd-numbered parasegments, as well as parasegment 6. Because
      these parasegments straddle segment boundaries, we observe fusions between
      adjacent segments. Finally, expression of Of'E75A in the blastoderm requires even
      skipped, which is a gap gene in Oncopeltus. These data show that the function of
      Of'E75A during embryogenesis shares many properties with canonical pair-rule
      genes in other insects. They further suggest that parasegment specification may
      occur through irregular and episodic pair-rule-like activity.

PMID- 19580802
TI  - Isl1 is a direct transcriptional target of Forkhead transcription factors in
      second-heart-field-derived mesoderm.
AB  - The cells of the second heart field (SHF) contribute to the outflow tract and
      right ventricle, as well as to parts of the left ventricle and atria. Isl1, a
      member of the LIM-homeodomain transcription factor family, is expressed early in
      this cardiac progenitor population and functions near the top of a
      transcriptional pathway essential for heart development. Isl1 is required for the
      survival and migration of SHF-derived cells into the early developing heart at
      the inflow and outflow poles. Despite this important role for Isl1 in early heart
      formation, the transcriptional regulation of Isl1 has remained largely undefined.
      Therefore, to identify transcription factors that regulate Isl1 expression in
      vivo, we screened the conserved noncoding sequences from the mouse Isl1 locus for
      enhancer activity in transgenic mouse embryos. Here, we report the identification
      of an enhancer from the mouse Isl1 gene that is sufficient to direct expression
      to the SHF and its derivatives. The Isl1 SHF enhancer contains three consensus
      Forkhead transcription factor binding sites that are efficiently and specifically
      bound by Forkhead transcription factors. Importantly, the activity of the
      enhancer is dependent on these three Forkhead binding sites in transgenic mouse
      embryos. Thus, these studies demonstrate that Isl1 is a direct transcriptional
      target of Forkhead transcription factors in the SHF and establish a
      transcriptional pathway upstream of Isl1 in the SHF.

PMID- 19580804
TI  - Coordinating the timing of cardiac precursor development during gastrulation: a
      new role for Notch signaling.
AB  - Notch signaling has been shown to mediate a wide array of cell fate decisions
      during development. While previous work has demonstrated that Notch signaling
      plays an important role in regulating cardiac differentiation and morphogenesis,
      an earlier role during cardiac field formation has not yet been fully
      characterized. Previously, our lab demonstrated that perturbations in Notch
      signaling beginning at the onset of gastrulation affect the subdivision of germ
      layers. However due to the potential additive effects of misregulating Notch
      signaling over multiple stages of development, it was not possible to distinguish
      a specific role for this pathway during heart field specification. Here, we
      developed an innovative approach that takes advantage of temporally inducible
      constructs to isolate our manipulations to specific windows of development. In
      particular, we focused our studies on some of the earliest stages of
      cardiogenesis when heart field specification occurs. Our findings demonstrate a
      novel role for Notch signaling during the prepatterning of the cardiac mesoderm.
      Specifically, once relieved of aberrantly activated Notch signaling following
      gastrulation, cardiac precursors retain the ability to express markers of the
      cardiac field. Conversely, downregulating Notch signaling in cells fated to
      become heart tissue results in the induction of cardiac field genes in gastrula
      embryos. Finally, we provide evidence suggesting that this new role for Notch
      signaling is mediated at least in part via the Notch effector protein, Esr9 and
      the transcription factor GATA4. Taken together, these findings provide strong
      evidence for a novel role for Notch signaling in regulating the timing of heart
      field specification during early cardiogenesis.

PMID- 19580805
TI  - Both inhibition and activation of Notch signaling rely on a conserved Neuralized
      binding motif in Bearded proteins and the Notch ligand Delta.
AB  - Lateral inhibition is one of the key functions of Notch signaling during animal
      development. In the proneural clusters that give rise to Drosophila
      mechanosensory bristles, Delta (Dl) ligand in the sensory organ precursor (SOP)
      cell is targeted for ubiquitination by the E3 ligase Neuralized (Neur), resulting
      in activation of Dl's capacity to signal to the Notch receptor on neighboring
      cells. The cells that receive this signal activate a genetic program that
      suppresses their SOP fate potential, insuring that only a single SOP develops
      within each cluster. Using multiple lines of investigation, we provide evidence
      that members of the Bearded family of proteins (BFMs) inhibit Dl activation in
      non-SOP cells by binding to Neur and preventing it from interacting with Dl. We
      show that this activity of BFMs is dependent on the conserved NXXN motif, and
      report the unexpected finding that several BFMs include multiple functional
      copies of this motif. We find that a conserved NXXN motif in the intracellular
      domain of Dl is responsible for its interaction with Neur, indicating direct
      competition between Dl and BFMs for binding to Neur, and we show that Neur
      dependent endocytosis of Dl requires the integrity of its NXXN motif. Our results
      illuminate the mechanism of an important regulatory event in Notch signaling that
      appears to be conserved between insects and crustaceans.

PMID- 19580806
TI  - Mechanism of glutamate-induced neurotoxicity in HT22 mouse hippocampal cells.
AB  - Glutamate is an endogenous excitatory neurotransmitter. At high concentrations,
      it is neurotoxic and contributes to the development of certain neurodegenerative
      diseases. There is considerable controversy in the literature with regard to
      whether glutamate-induced cell death in cultured HT22 cells (an immortalized
      mouse hippocampal cell line) is apoptosis, necrosis, or a new form of cell death.
      The present study focused on investigating the mechanism of glutamate-induced
      cell death. We found that glutamate induced, in a time-dependent manner, both
      necrosis and apoptosis in HT22 cells. At relatively early time points (8-12 h),
      glutamate induced mostly necrosis, whereas at late time points (16-24 h), it
      induced mainly apoptosis. Glutamate-induced mitochondrial oxidative stress and
      dysfunction were crucial early events required for the induction of apoptosis
      through the release of the mitochondrial apoptosis-inducing factor (AIF), which
      catalyzed DNA fragmentation (an ATP-independent process). Glutamate-induced cell
      death proceeded independently of the Bcl-2 family proteins and caspase
      activation. The lack of caspase activation likely resulted from the lack of
      intracellular ATP when the mitochondrial functions were rapidly disrupted by the
      mitochondrial oxidative stress. In addition, it was observed that activation of
      JNK, p38, and ERK signaling molecules was also involved in the induction of
      apoptosis by glutamate. In conclusion, glutamate-induced apoptosis is AIF
      dependent but caspase-independent, and is accompanied by DNA ladder formation but
      not chromatin condensation.

PMID- 19580807
TI  - CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in
      preclinical models of pain.
AB  - Zileuton, a redox and iron chelator 5-lipoxygenase (5-LOX) inhibitor and,
      leukotriene receptor antagonists are presently used clinically in the long term
      treatment of asthma. Recent data implicate 5-LOX pathway in pain signaling. We
      report 5-LOX expression in the central nervous system (CNS) and analyze the pain
      efficacy of a new class of non redox, non iron chelating 5-LOX inhibitor. CJ
      13610, 4-(3-(4-(2-methyl-1H-imidazol-1-yl) phenylthio) phenyl)-tetrahydro-2H
      pyran-4-carboxamide, demonstrated antihyperalgesic activity in inflammatory pain
      models including the acute carrageenan model and the chronic inflammatory model
      using complete Freund's adjuvant. Following complete Freund's adjuvant stimulus
      leukotrieneB(4) concentration in the brain was elevated (9+/-1 ng/g, mean+/
      S.E.M.) by about 3 times that of the control group (3+/-0.11, mean+/-S.E.M.).
      Hyperalgesia and leukotrieneB(4) concentration were both reversed following CJ
      13610 treatment. Furthermore, we demonstrate CJ-13610 efficacy against
      osteoarthritis like pain using the rat medial meniscal transection model. CJ
      13610 at oral doses of 0.6, 2 and 6 mg/kg/day reversed two modalities of pain in
      this model; tactile allodynia and weight bearing differential. Taken together,
      these data suggest that 5-LOX pathway and the leukotriene products are important
      mediators of pain.

PMID- 19580809
TI  - (Pro)renin receptor is expressed in human retinal pigment epithelium and
      participates in extracellular matrix remodeling.
AB  - The (pro)renin receptor (PRR) is believed to potentiate the renin-angiotensin
      system (RAS), conferring to prorenin, a likely pathological role at tissue level.
      The PRR has been identified in the microvascular endothelial cells of the retina,
      in which it seems to be involved in pathological neovascularization processes. In
      the present study, we sought to explore PRR expression and prorenin action in
      human retinal pigment epithelium (RPE) cells, as well as its potential
      implication in extracellular matrix (ECM) turnover. Isolated RPE cells from donor
      human eyes as well as freshly isolated human retinas demonstrated expression of
      PRR at mRNA and protein levels. Moreover, we demonstrate that PRR expressed in
      the RPE cells is functional, as shown by prorenin-induced increases in Erk1/2
      phosphorylation. PRR expression was also shown to be regulated by its main
      physiological agonist prorenin. We found evidence that the PRR may be involved in
      ECM-remodeling processes through a prorenin-induced upregulation of type I
      collagen. Immunostaining analysis of human retinas revealed higher PRR and type I
      collagen expression in the RPE of eye donors with dry age-related macular
      degeneration (AMD) and hypertension, supporting the in vitro findings using human
      isolated RPE cells. Taken together, the present study demonstrates for the first
      time that the PRR is expressed in human RPE and suggests a molecular mechanism by
      which hypertension may exacerbate the pathology of dry AMD.

PMID- 19580808
TI  - Hsp27 associates with the titin filament system in heat-shocked zebrafish
      cardiomyocytes.
AB  - Injury to muscle tissue plays a central role in various cardiovascular
      pathologies. Overexpression of the small heat shock protein Hsp27 protects muscle
      cells against thermal, oxidative and ischemic stress. However, underlying
      mechanisms of this protection have not been resolved. A distinctive feature of
      muscle cells is the stress-induced association of Hsp27 with the sarcomere. The
      association of Hsp27 with the cytoskeleton, in both muscle and non-muscle cells,
      is thought to represent interaction with Z-line components or filamentous actin.
      Here, we examined the association of Hsp27 with myofibrils in adult zebrafish
      myocardium subjected to hyperthermia and mechanical stretching. Consistent with
      previously published results, Hsp27 in resting length myofibrils localized to
      narrowly defined regions, or bands, which colocalized with Z-line markers.
      However, analysis of stretched myofibrils revealed that the association of Hsp27
      with myofibrils was independent of desmin, alpha-actinin, myosin, and filamentous
      actin. Instead, Hsp27 maintained a consistent relationship with a marker for the
      titin A/I border over various sarcomeric lengths. Finally, extraction of actin
      filaments revealed that Hsp27 binds to a component of the remaining sarcomere.
      Together, these novel data support a mechanism of Hsp27 function where
      interactions with the titin filament system protect myofibrils from stress
      induced degradation.

PMID- 19580810
TI  - Modulating the hypoxia-inducible factor signaling pathway as a therapeutic
      modality to regulate retinal angiogenesis.
AB  - Hypoxia-inducible factor (HIF) signaling cascade plays a critical role in
      angiogenesis by activating the transcription of genes encoding angiogenic growth
      factors. This study evaluated the effects of YC-1, a HIF-1 inhibitor, on the
      morphological, biochemical and molecular changes in human retinal microvascular
      endothelial cells. We found that YC-1 suppressed vascular endothelial cell
      proliferation, migration and tube formation, while it significantly increased the
      proteasome activity. Moreover, YC-1 induced a G(0)/G(1) cell-cycle arrest,
      whereas it exerted only an insignificant proapoptotic effects. Under normoxia or
      hypoxia, YC-1 did not alter the morphology or the cell viability. Additionally,
      under hypoxic conditions, YC-1 downregulated HIF-2alpha, VEGF, EPO, ET-1, and MMP
      9 mRNA and protein levels, this was accompanied by a significant decrease in the
      MMP-9 activity. YC-1 decreased the basal expression of HIF-1alpha protein under
      normoxia, whereas it inhibited HIF-1alpha protein synthesis, stability, and
      nuclear translocation mechanisms under hypoxia. Furthermore, in a 3D collagen
      matrix model using mouse retinal explants cultured under normoxic and hypoxic
      conditions, YC-1; (1) inhibited outgrowth of new vessel sprouts; (2) reduced VEGF
      expression; (3) dramatically decreased the vessels immunoreactivities for CD31
      and von Willebrand Factor (vWF); and (4) was highly effective in reducing the
      vascular density within the retina, compared to controls. These findings indicate
      that YC-1 possesses several antiangiogenic properties, both in vitro and ex vivo,
      which could be exploited as valuable therapeutic potentials to inhibit formation
      and the growth of new retinal vessels in the hypoxic retina.

PMID- 19580812
TI  - Acanthamoeba affects the integrity of human brain microvascular endothelial cells
      and degrades the tight junction proteins.
AB  - Haematogenous spread is a key step in the development of Acanthamoeba
      granulomatous encephalitis, however it is not clear how circulating amoebae cross
      the blood-brain barrier to enter the CNS to produce disease. Using the primary
      human brain microvascular endothelial cells (HBMEC), which constitute the blood
      brain barrier, here it is shown that Acanthamoeba abolishes the HBMEC
      transendothelial electrical resistance. Using traversal assays, it was observed
      that Acanthamoeba crosses the HBMEC monolayers. The primary interactions of
      Acanthamoeba with the HBMEC resulted in increased protein tyrosine
      phosphorylations and the activation of RhoA, suggesting host-parasite cross-talk.
      Furthermore, Western blot assays revealed that Acanthamoeba degraded occludin and
      zonula occludens-1 proteins in a Rho kinase-dependent manner. Overall, these
      findings suggest that Acanthamoeba affects the integrity of the monolayer and
      traverses the HBMEC by targeting the tight junction proteins.

PMID- 19580811
TI  - Autocrine regulation of early embryonic development by the artemin-GFRA3 (GDNF
      family receptor-alpha 3) signaling system in mice.
AB  - Development of early embryos is regulated by autocrine/paracrine factors.
      Analyzing the expression of polypeptide ligand-receptor pairs using DNA
      microarray datasets, we identified transcripts for artemin, a member of the GDNF
      (glial cell line-derived neurotrophic factor) family, its receptor GFRA3 (GDNF
      family receptor-alpha 3) and coreceptor RET. Here we report an
      autocrine/paracrine role of the artemin-GFRA3 signaling system in regulating
      early embryonic development and apoptosis. Possible involvement of the MAP kinase
      signaling pathway was also demonstrated. The genome-wide survey of ligand
      receptor pairs and early embryo cultures provided a better understanding of
      autocrine/paracrine embryonic factors important for optimal blastocyst
      development.

PMID- 19580813
TI  - A common structural basis for pH- and calmodulin-mediated regulation in plant
      glutamate decarboxylase.
AB  - Glutamate decarboxylase (Gad) catalyzes glutamate to gamma-aminobutyrate
      conversion. Plant Gad is a approximately 340 kDa hexamer, involved in development
      and stress response, and regulated by pH and binding of Ca(2+)/calmodulin (CaM)
      to the C-terminal domain. We determined the crystal structure of Arabidopsis
      thaliana Gad1 in its CaM-free state, obtained a low-resolution structure of the
      calmodulin-activated Gad complex by small-angle X-ray scattering and identified
      the crucial residues, in the C-terminal domain, for regulation by pH and CaM
      binding. CaM activates Gad1 in a unique way by relieving two C-terminal
      autoinhibition domains of adjacent active sites, forming a 393 kDa Gad1-CaM
      complex with an unusual 1:3 stoichiometry. The complex is loosely packed: thanks
      to the flexible linkers connecting the enzyme core with the six C-terminal
      regulatory domains, the CaM molecules retain considerable positional and
      orientational freedom with respect to Gad1. The complex thus represents a
      prototype for a novel CaM-target interaction mode. Thanks to its two levels of
      regulation, both targeting the C-terminal domain, Gad can respond flexibly to
      different kinds of cellular stress occurring at different pH values.

PMID- 19580814
TI  - Direct optical microscopic observation of the microtubule polymerization
      intermediate sheet structure in the presence of gas7.
AB  - The process of microtubule elongation is thought to consist of two stages
      formation of a tubulin sheet structure and its closure into a tube. However, real
      time observation of this process has been difficult. Here, by utilizing phospho
      tau binding protein Gas7 (growth-arrest-specific protein 7), we visualized the
      polymer transformation process by dark-field microscopy. Upon elongation, thin
      and flexible structures, often similar to a curved hook, appeared at the end of
      microtubules. Electron microscopic observations supported the idea that these
      flexible structures are tubulin sheets. They maintained their length until they
      gradually became thick and rigid beginning in the central portion, resulting in
      straight microtubules. In the absence of Gas7, the sheet-like structure was
      rarely observed; moreover, when observed, it was fragile and engaged in typical
      dynamic instability. With Gas7, no catastrophe was observed. These results
      suggest that Gas7 enhances microtubule polymerization by stabilizing sheet
      intermediates and is a useful tool for analyzing microtubule transformation.

PMID- 19580815
TI  - Nucleic acid binding activity of human Cockayne syndrome B protein and
      identification of Ca(2+) as a novel metal cofactor.
AB  - The Cockayne syndrome group B protein (CSB) is a member of the SWI/SNF2 subgroup
      of Superfamily 2 ATPases/nucleic acid translocases/helicases and is defective in
      the autosomal recessive segmental progeroid disorder Cockayne syndrome. This
      study examines the ATP-dependent and the ATP-independent biochemical functions of
      human CSB. We show that Ca(2+) is a novel metal cofactor of CSB for ATP
      hydrolysis, mainly through the enhancement of k(cat), and that a variety of
      biologically relevant model nucleic acid substrates can function to activate CSB
      ATPase activity with either Mg(2+) or Ca(2+) present. However, CSB lacked
      detectable ATP-dependent helicase and single- or double-stranded nucleic acid
      translocase activities in the presence of either divalent metal. CSB was found to
      support ATP-independent complementary strand annealing of DNA/DNA, DNA/RNA, and
      RNA/RNA duplexes, with Ca(2+) again promoting optimal activity. CSB formed a
      stable protein:DNA complex with a 34mer double-stranded DNA in electrophoretic
      mobility-shift assays, independent of divalent metal or nucleotide (e.g. ATP).
      Moreover, CSB was able to form a stable complex with a range of nucleic acid
      substrates, including bubble and "pseudo-triplex" double-stranded DNAs that
      resemble replication and transcription intermediates, as well as forked duplexes
      of DNA/DNA, DNA/RNA, and RNA/RNA composition, the latter two of which do not
      promote CSB ATPase activity. Association of CSB with DNA, independent of ATP
      binding or hydrolysis, was seemingly sufficient to displace or rearrange a stable
      pre-bound protein:DNA complex, a property potentially important for its roles in
      transcription and DNA repair.

PMID- 19580817
TI  - Mutagenesis of important amino acid reveals unconventional homologous
      internalization of beta(1)-adrenergic receptor.
AB  - AIMS: The study was designed to examine the internalization of Asp104Lys mutant
      of beta(1)-adrenergic receptor (beta(1)-AR) and compared to other mutant
      (Asp104Ala) and wild type receptors. Moreover, this study needs to perform the
      role of GRK2 (betaARK1) and beta-arrestin1 on this internalization of Asp104Lys
      mutant of beta(1)-AR. MAIN METHODS: Binding affinity, functional potency of
      agonist and agonist-induced internalization were determined for wild type and
      both mutants of beta(1)-ARs stably expressed in HEK 293 cells as assessed by
      [(3)H] CGP12177 radioligand. We have performed GRK2 and beta-arrestin1 expression
      levels by western blot analysis and also performed internalization of this mutant
      receptor after over expression and deletion of beta-arrestin1 gene. KEY FINDINGS:
      In the present study, the binding affinity of (-)-isoproterenol for both mutants
      were significantly decreased compared to wild type. Though the mutant Asp104Ala
      showed agonist-induced receptor activation, interestingly this mutant was not
      internalized. However, the mutant Asp104Lys, which showed uncoupling with G
      protein, was internalized 31.77+/-3.13% from cell surface. Asp104Lys mutant
      produced the same level of GRK2 expression in (-)-isoproterenol induced
      stimulation of wild type receptor and addition of (-)-isoproterenol further
      increased GRK2 expression in mutant receptors. In addition, overexpression of
      beta-arrestin1 in mutant Asp104Lys promoted (39.75+/-2.19%) and knockdown of beta
      arrestin1 by siRNA decreased (3.55+/-1.75%) internalization compared to Asp104Lys
      mutant of beta(1)-ARs. SIGNIFICANCE: The present studies suggest that Asp104Lys
      mutant beta(1)-ARs triggers unconventional homologous internalization induced by
      G protein independent signals, where GRK2 and beta-arrestin1 play an important
      role for beta(1)-AR internalization.

PMID- 19580816
TI  - Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram
      Syndrome 2.
AB  - The endoplasmic reticulum protein Miner1 is essential for health and longevity.
      Mis-splicing of CISD2, which codes for Miner1, is causative in Wolfram Syndrome 2
      (WFS2) resulting in early onset optic atrophy, diabetes mellitus, deafness and
      decreased lifespan. In knock-out studies, disruption of CISD2 leads to
      accelerated aging, blindness and muscle atrophy. In this work, we characterized
      the soluble region of human Miner1 and solved its crystal structure to a
      resolution of 2.1 A (R-factor=17%). Although originally annotated as a zinc
      finger, we show that Miner1 is a homodimer harboring two redox-active 2Fe-2S
      clusters, indicating for the first time an association of a redox-active FeS
      protein with WFS2. Each 2Fe-2S cluster is bound by a rare Cys(3)-His motif within
      a 17 amino acid segment. Miner1 is the first functionally different protein that
      shares the NEET fold with its recently identified paralog mitoNEET, an outer
      mitochondrial membrane protein. We report the first measurement of the redox
      potentials (E(m)) of Miner1 and mitoNEET, showing that they are proton-coupled
      with E(m) approximately 0 mV at pH 7.5. Changes in the pH sensitivity of their
      cluster stabilities are attributed to significant differences in the
      electrostatic distribution and surfaces between the two proteins. The structural
      and biophysical results are discussed in relation to possible roles of Miner1 in
      cellular Fe-S management and redox reactions.

PMID- 19580818
TI  - Chronic morphine treatment induces functional delta-opioid receptors in amygdala
      neurons that project to periaqueductal grey.
AB  - Chronic morphine treatment and persistent pain stimuli trigger translocation of
      delta-opioid receptors (DORs) from cytosolic pools to the surface membrane.
      Previously, we reported that chronic treatment with morphine induces functional
      DORs on GABAergic nerve terminals impinging on some neurons in the midbrain
      periaqueductal grey. In the present investigation, we used chronic administration
      of morphine in adult rats to study delta and mu-opioid receptors in the central
      nucleus of amygdala (CeA), a brain region with a substantial (presumed) GABAergic
      projection to the periaqueductal grey. Chronic morphine treatment increased the
      proportion of neurons displaying an increased potassium conductance in response
      to a selective DOR-agonist. There was a corresponding reduction in responsiveness
      of CeA neurons to a selective mu-opioid agonist. By combining retrograde
      labelling and live cell recording of CeA-periaqueductal grey projection neurons,
      we found nearly all (6/7 or 86%) projection neurons responded to delta agonist
      after chronic treatment with morphine versus only 2/7 neurons (29%) from vehicle
      treated animals. Other physiological properties of amygdala neurons did not
      differ between neurons from vehicle and morphine-treated animals. Taken together,
      these results indicate that chronic treatment with morphine upregulates
      functional DORs in neurons projecting from the CeA to periaqueductal grey. CeA
      periaqueductal grey projections form part of the descending antinociceptive and
      autonomic control systems suggesting an upregulation of functional DOR in
      antinociception, emotion and anxiety following chronic morphine treatment.

PMID- 19580819
TI  - l-kynurenine combined with probenecid and the novel synthetic kynurenic acid
      derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal
      nucleus.
AB  - Systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG)
      triggers a delayed attack without aura in many migraineurs, but not in healthy
      volunteers. In rats, 4 h after the systemic administration of NTG (10 mg/kg bw,
      s.c.), the neurons of the caudal trigeminal nucleus (TNC) are activated and the
      expression of neuronal NO synthase (nNOS) in the same area is increased
      suggesting a self-amplifying process in the trigeminal system, which seems to be
      crucial in migraine pathogenesis. Kynurenic acid (KYNA) and its analogues may
      exert modulatory effects in many neuropathological conditions, probably via N
      methyl-D-aspartate (NMDA) antagonism. Since NMDA receptors play a crucial role in
      trigeminal pain processing, the aim of our experiments was to compare the effects
      of L-kynurenine (L-KYN) combined with probenecid (PROB) or with 2-(2-N,N
      dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride alone, a
      newly synthetized KYNA derivative, on the NTG-induced nNOS expression in the rat
      TNC. Pretreatment with L-KYN (300 mg/kg bw, i.p.) together with PROB (200 mg/kg
      bw, i.p.) and KYNA derivative (300 mg/kg bw, i.p.) attenuated the NTG-induced
      nNOS expression in the rat TNC. Our data suggest that the stimulating effect of
      NTG, and thus of NO, on the expression of nNOS might be modulated by increasing
      the KYNA level in the brain, probably through the NMDA receptors. These data
      could help promote a better understanding of the pathogenesis of headaches and
      the action of antimigraine drugs.

PMID- 19580822
TI  - Radial frequency adaptation reveals interacting contour shape channels.
AB  - Combinations of radial frequency (RF) patterns may be used to represent the
      contours of complex shapes. Previous work has shown that many radial frequency
      patterns are processed globally and multiple curvature mechanisms have been
      proposed to account for human performance in detecting these patterns. The
      current paper provides a direct test of this proposal and also, investigates how
      different RF mechanisms interact when forming a single complex contour. To test
      for interactions, pairs of RF components have been combined on a closed contour
      to create a compound pattern. Deformation detection thresholds for single RF
      components were compared to thresholds for detecting that component in a
      compound. Masking was present, and was not tuned for the phase relationship
      between components but was instead tuned for RF, consistent with the existence of
      several narrow-band shape channels which have inhibitory connections between
      them. Adaptation was then used to selectively desensitise channels. Adapting to a
      single RF pattern reduced sensitivity to RF patterns of the same frequency but
      restored sensitivity to a dissimilar RF component on the compound contour. The
      effects were shown to be independent of the mean radius of the adaptor, and also
      occurred when adaptors were contours composed of contrast modulated noise,
      suggesting that post-adaptation results are not simply due to adaptation of local
      V1 orientation-tuned simple cells. The data are consistent with two or more shape
      channels for closed-contours, which operate in a competitive network.

PMID- 19580820
TI  - Vasopressin mediates enhanced offspring protection in multiparous rats.
AB  - Maternal aggression is highly expressed during lactation and serves to protect
      the developing young from intruders that may injure the offspring. One
      neurochemical modulator of maternal aggression appears to be arginine vasopressin
      (AVP). Earlier research supports a role for AVP in maternal aggression in rats as
      treatment with an AVP antagonist in lactating, primiparous rats stimulates the
      mother's aggression towards intruders the second half of lactation, but AVP
      itself was without major effects during early lactation. Recent behavioral
      findings indicate that during a second lactation (multiparous) mothers display
      higher levels of maternal aggression than do first time mothers (primiparous).
      The present study was designed to assess the involvement of AVP as mothers
      acquire reproductive experience. Therefore, the involvement of AVP in maternal
      aggression in multiparous mothers was measured after intracerebroventricular
      (ICV) treatment with both AVP and a V1a receptor antagonist. Behavior was
      assessed during early lactation when aggression levels are very high in
      multiparous mothers as well as during late lactation when aggression levels are
      lower. The results demonstrated that ICV infusions of AVP significantly reduced
      maternal aggression in multiparous females on day 5 of lactation, whereas V1a
      antagonist infusions increased aggression on day 15 of lactation. These findings
      suggest that the role of AVP in maternal aggression may be amplified as
      reproductive/lactational experiences increase, and support the involvement of the
      central AVP system as a key modulator of maternal protection of the young.

PMID- 19580821
TI  - Advantages of the multiple case series approach to the study of cognitive
      deficits in autism spectrum disorder.
AB  - In the neuropsychological case series approach, tasks are administered that tap
      different cognitive domains, and differences within rather than across
      individuals are the basis for theorising; each individual is effectively their
      own control. This approach is a mainstay of cognitive neuropsychology, and is
      particularly suited to the study of populations with heterogeneous deficits.
      However it has very rarely been applied to the study of cognitive differences in
      autism spectrum disorder (ASD). Here, we investigate whether this approach can
      yield information beyond that given by the typical group study method, when
      applied to an ASD population. Twenty-one high-functioning adult ASD participants
      and 22 IQ, age, and gender-matched control participants were administered a large
      battery of neuropsychological tests that would represent a typical
      neuropsychological assessment for neurological patients in the United Kingdom.
      The data were analysed using both group and single-case study methods. The group
      analysis revealed a limited number of deficits, principally on tests with a large
      executive function component, with no impairment in more routine abilities such
      as basic attending, language and perception. Single-case study analysis proved
      more fruitful revealing evidence of considerable variation in abilities both
      between and within ASD participants. Both sub-normal and supra-normal performance
      were observed, with the most defining feature of the ASD group being this
      variability. We conclude that the use of group-level analysis alone in the study
      of cognitive deficits in ASD risks missing cognitive characteristics that may be
      vitally important both theoretically and clinically, and even may be misleading
      because of averaging artifact.

PMID- 19580823
TI  - A method for oral administration of hydrophilic substances to Caenorhabditis
      elegans: Effects of oral supplementation with antioxidants on the nematode
      lifespan.
AB  - Numerous studies using Caenorhabditis elegans have used a protocol in which
      chemicals are orally delivered by incorporating them into the nematode growth
      media or mixing them with the food bacteria. However, actual exposure levels are
      difficult to estimate as they are influenced by both the rates of ingestion into
      the intestine as well as absorption from the intestinal lumen. We used liposomes
      loaded with the hydrophilic fluorescent reagent uranin to test oral
      administration of water-soluble substances to C. elegans. Ingestion of liposomes
      loaded with fluorescent dye resulted in successful oral delivery of chemicals
      into the intestines of C. elegans. Using liposomes, oral administration of
      hydrophilic antioxidants (ascorbic acid, N-acetyl-cysteine, reduced glutathione,
      and thioproline) prolonged the lifespan of the nematodes, whereas the
      conventional method of delivery showed neither fluorescence nor longevity
      effects. Our method efficiently and quantitatively delivers solutes to nematodes.

PMID- 19580824
TI  - Human genetic variations: Beacons on the pathways to successful ageing.
AB  - Avoiding age-related disease until late in life is key to 'successful' ageing.
      Over 300 genome-wide association study papers have been published. Over 50
      variants have already been identified as associated with four key age-related
      diseases, namely cardiovascular disease, type 2 diabetes, osteoporosis and
      prostate cancer. We review these findings with reference to pathways linked to
      ageing, including cell cycle control or cell senescence, oxidative stress,
      insulin, IGF1 and other endocrine signalling, and inflammation. Many variants are
      disease specific or of unknown function. Of the remainder, those with functions
      likely to be relevant to ageing are predominantly in cell cycle control and
      therefore tissue repair. Three loci associated with two or more age-related
      diseases have been identified, two apparently related to cell cycle control. The
      third shared locus (near TERT), may be involved in telomerase activity and is
      associated with several environmentally caused age-related cancers. These
      findings challenge current ideas, suggesting large numbers of cell type specific
      effects, often driven by regulatory rather than coding changes. They also confirm
      the central role of cell cycle and re-growth as a key pathway underlying the
      human variation in successful ageing.

PMID- 19580825
TI  - Comparative studies of the neuro-excitatory behavioural effects of morphine-3
      glucuronide and dynorphin A(2-17) following spinal and supraspinal routes of
      administration.
AB  - Morphine-3-glucuronide (M3G) administered centrally produces dose-dependent neuro
      excitatory behaviours in rodents via a predominantly non-opioid mechanism. The
      endogenous opioid peptide, dynorphin A (Dyn A) (1-17), is rapidly cleaved in vivo
      to the relatively more stable fragment Dyn A(2-17) which also produces excitatory
      behaviours in rodents via a non-opioid mechanism. This study investigated the
      possible contribution of Dyn A(2-17) to the neuro-excitatory behaviours evoked by
      supraspinally and spinally administered M3G in male Sprague-Dawley (SD) rats.
      Marked qualitative differences in behaviours were apparent following
      administration of M3G and Dyn A(2-17). Administration of 11 nmol i.c.v. doses of
      M3G produced intermittent myoclonic jerks, tonic-clonic convulsions, and ataxia,
      as well as postural changes, whereas i.c.v. Dyn A(2-17) at 15 nmol produced
      effects on body posture alone. Administration of 11 nmol i.t. doses of M3G
      produced intermittent explosive motor activity, and touch-evoked agitation, as
      well as postural changes, whereas i.t. Dyn A(2-17) at 15 nmol produced postural
      changes, touch-evoked agitation, and paralysis. Pre-treatment with Dyn A
      antiserum (200 microg) markedly attenuated total behavioural excitation following
      i.c.v. and i.t. administration of Dyn A(2-17) by approximately 94% and 78%,
      respectively. However, total behavioural excitation following i.c.v. and i.t.
      administration of M3G was less markedly attenuated (both approximately 27%) by
      pre-treatment with Dyn A antiserum, with reductions in tonic-clonic convulsions (
      approximately 43%), explosive motor behaviour ( approximately 28%), and touch
      evoked agitation ( approximately 22%). The present findings discount a major role
      for Dyn A in mediating the neuro-excitatory effects of M3G, although it may
      contribute to maintaining some individual neuro-excitatory behaviours.

PMID- 19580826
TI  - Mammalian phosphoinositide kinases and phosphatases.
AB  - Phosphoinositides are lipids that are present in the cytoplasmic leaflet of a
      cell's plasma and internal membranes and play pivotal roles in the regulation of
      a wide variety of cellular processes. Phosphoinositides are molecularly diverse
      due to variable phosphorylation of the hydroxyl groups of their inositol rings.
      The rapid and reversible configuration of the seven known phosphoinositide
      species is controlled by a battery of phosphoinositide kinases and
      phosphoinositide phosphatases, which are thus critical for phosphoinositide
      isomer-specific localization and functions. Significantly, a given
      phosphoinositide generated by different isozymes of these phosphoinositide
      kinases and phosphatases can have different biological effects. In mammals, close
      to 50 genes encode the phosphoinositide kinases and phosphoinositide phosphatases
      that regulate phosphoinositide metabolism and thus allow cells to respond rapidly
      and effectively to ever-changing environmental cues. Understanding the distinct
      and overlapping functions of these phosphoinositide-metabolizing enzymes is
      important for our knowledge of both normal human physiology and the growing list
      of human diseases whose etiologies involve these proteins. This review summarizes
      the structural and biological properties of all the known mammalian
      phosphoinositide kinases and phosphoinositide phosphatases, as well as their
      associations with human disorders.

PMID- 19580827
TI  - An investigation of cross-modal plasticity of effective connectivity in the blind
      by dynamic causal modeling of functional MRI data.
AB  - To investigate connectivity between primary somatosensory area (S1) and striate
      cortex (V1) in the blind, we used dynamic causal modeling of functional MRI
      acquired while 15 blind (9 early-onset and 6 late-onset) and 24 sighted subjects
      performed a tactile Braille discrimination task with their right hand. Five
      regions of interest were selected from either the ventral or dorsal pathways:
      left S1, anterior intraparietal sulcus (aIPS), superior occipital gyrus (SOG),
      inferior occipital gyrus (IOG), and V1. Bayesian model comparison showed that a
      cortico-cortical feedback pathway model without direct connections between V1 and
      S1 performed better than that with direct connections. In the blind, baseline
      connectivity and its discrimination-specific modulation in aIPS-SOG and aIPS-IOG
      were positive and bi-directional, while they were negative in the sighted. Thus
      visual deprivation may induce reorganization of the visual cortical areas due to
      the competitive shift for tactile inputs. The early blind showed stronger
      connectivity than the late blind in the dorsal pathway (aIPS-V1 through SOG) and
      in SOG-IOG bi-directionally. Task performance positively correlated with baseline
      connectivity of SOG-V1 and SOG-IOG across blind subjects. Therefore, dorsal
      visual regions are involved in the functional shift in V1 from visual to tactile
      information processing in blind subjects.

PMID- 19580828
TI  - Genetic typing of equine influenza virus isolated in Poland in 2005 and 2006.
AB  - Two equine influenza virus strains were isolated from horses during the local
      respiratory disease outbreaks in Poland in 2005 and 2006. The H3 equine influenza
      viral RNA was amplified directly from the clinical specimens with RT-PCR and HA1
      fragments were sequenced. The highest homology of HA1 nucleotide sequences of
      A/eq/Pulawy/05 with A/eq/Aboyne/1/05 and A/eq/Pulawy/06 with A/eq/Essex/2/05 was
      found. The phylogenetic analysis based on amino acid sequences of HA1 fragments
      of 84 equine influenza virus strains isolated in Europe during the period of 1976
      2007 was conducted to determine the evolutionary relationship of the two Polish
      and the other European isolates. The resulting phylogenetic tree clearly
      clustered A/eq/Pulawy/05 with the strains belonging to the European lineage of
      the equine influenza virus. On the other hand A/eq/Pulawy/06 was placed in the
      Florida sub-lineage of the American type strains. The presence of the same amino
      acids: methionine, asparagine and threonine at the positions 48, 159 and 163
      respectively, in both Polish isolates, despite the fact that the strains are
      grouped in two different lineages may indicate the existence of the common
      ancestor. It is possible that A/eq/Pulawy/06 evolved locally rather than was
      introduced.

PMID- 19580829
TI  - DNA tattoo vaccination: effect on plasmid purity and transfection efficiency of
      different topoisoforms.
AB  - Recently, DNA tattooing was introduced as novel intradermal administration
      technique for plasmid DNA (pDNA) vaccines. The aim of this study was to determine
      if tattooing affects the integrity of pDNA (reduction in supercoiled (SC)
      content) and whether a change in pDNA topology would affect antigen expression
      and immune response. We show that 1.) in vitro tattooing of pDNA solutions
      results in minor damage to pDNA (<or=3% SC pDNA reduction) and only open circular
      (OC) pDNA formation, 2.) antigen expression and T-cell responses upon tattoo
      administration of SC and OC pDNA are equal in a murine model, 3.) SC pDNA gives a
      significantly higher antigen expression than OC and linear pDNA in ex vivo human
      skin, 4.) pDNA topology does not influence antigen expression when formulated as
      PEGylated polyplexes. We conclude that a 3% reduction in SC purity most likely
      will have little or no effect on clinical antigen expression and T-cell
      responses. For intradermal tattoo administration the ex vivo skin model might be
      more suitable than the standard murine model for distinguishing subtle
      alterations in antigen expression of clinical pDNA formulations. The results from
      this study enable justification of release and shelf-life specifications of pDNA
      products applied by this specific route of administration, as requested by the
      regulatory authorities (>or=80% SC).

PMID- 19580831
TI  - The osteogenic effect of bone morphogenetic protein-2 on the collagen scaffold
      conjugated with antibodies.
AB  - Considerable research has been focused on the exploration of bone morphogenetic
      protein-2 (BMP(2)) delivery vehicles for achieving prolonged availability and
      maintaining efficient local concentration at the bone injury sites. In this
      study, heterobifunctional cross-linkers Sulfo-SMCC and cyclic thioimidate
      compound Traut's Reagent were used to conjugate monoclonal polyhistidine antibody
      on collagen scaffold demineralized bone matrix (DBM) to create specific binding
      between BMP(2) containing six histidines tag (His-BMP(2)) and DBM. According to
      the optimized cross-linking reagent concentration, more polyhistidine antibodies
      conjugated on DBM with 5mg/ml Traut's Reagent and 25ug/ml Sulfo-SMCC than
      physical adsorption. Monoclonal antibodies conjugated DBM (MAbs-DBM) could bind
      more His-BMP(2) than DBM and achieved controlled release in vitro. The alkaline
      phophatase (AP) activity of C2C12 cells on MAbs-DBM indicated that His-BMP(2)
      retained on MAbs-DBM preserved the function to induce osteogenic differentiation.
      His-BMP(2)/MAbs-DBM induced more ectopic bone formation (AP activity assay and
      histochemistry stain) than control group after subcutaneous implantation. The
      results demonstrated that antibody-collagen system could be useful for
      maintaining higher local therapy concentration of growth factors at the injury
      sites.

PMID- 19580830
TI  - Missing pieces in understanding the intracellular trafficking of polycation/DNA
      complexes.

PMID- 19580832
TI  - Which human leukocyte antigen antibodies are really clinically relevant?

PMID- 19580833
TI  - Changes in activatory and inhibitory natural killer (NK) receptors may induce
      progression to multiple myeloma: implications for tumor evasion of T and NK
      cells.
AB  - The molecular basis of monoclonal gammopathy of undetermined significance (MGUS)
      progression to a malignant monoclonal gammopathy remains poorly understood. It
      was recently suggested that this process involves the suppression of innate and
      adaptive immunity. In this study, we examined immunogenic differences in bone
      marrow plasma cells among individuals without gammopathy (controls) and patients
      with MGUS, multiple myeloma (MM), and plasma cell leukemia. We detected
      differences in major histocompatibility complex (MHC) class I expression, MHC
      class I chain-related molecule A, and CD95 that were more evident between MGUS
      and MM samples; there appeared to be a critical imbalance between natural killer
      (NK)-cell activating and inhibitory signals during the transition from MGUS to
      MM. Our results indicate that the human leukocyte antigen (HLA) class I(bright),
      MICA(dim/-), and CD95(dim/-) immunophenotype reported in myeloma cells may result
      from an extensive interaction of malignant cells with cytotoxic T and NK cells
      and appears to be immunoedited for the evasion of immunosurveillance.

PMID- 19580835
TI  - Clinical manifestation of mannose-binding lectin deficiency in adults independent
      of concomitant immunodeficiency.
AB  - Mannose-binding lectin (MBL) mediates important functions within the innate
      immune system, and its deficiency was associated with infectious complications.
      However, in adults without concomitant immunodeficiency the clinical relevance of
      MBL deficiency remains controversial. We analyzed the distribution of MBL
      deficiency and its association with concomitant immunodeficiency in 228 adult
      Caucasian patients with a history of recurrent and/or severe infections. Two
      hundred forty-one unrelated Caucasians without recurrent or severe infections
      served as control subjects. The frequency of severe MBL deficiency (plasma levels
      <or= 50 ng/ml) was significantly higher in patients with a history of recurrent
      and/or severe infections (p < 0.05, odds ratio 2.1, 95% confidence interval 1.1
      4.1), and this association was independent of concomitant antibody or cellular
      immunodeficiency. Our data challenge the view that MBL deficiency in adulthood
      becomes relevant only in individuals who are immunocompromised for other reasons.

PMID- 19580837
TI  - Epitopes of human leukocyte antigen class I antibodies found in sera of normal
      healthy males and cord blood.
AB  - This study defines 96 epitopes targeted by human leukocyte antigen (HLA)
      antibodies reported in the sera of normal healthy males with no history of
      deliberate alloimmunizations and in cord blood. These epitopes are accessible for
      antibody binding on either the intact or the dissociated forms of recombinant HLA
      class I single antigens. Sixty percent of the epitopes are accessible on
      dissociated antigens, are defined mostly by hidden amino acids, and are
      designated as cryptic epitopes. All 96 epitopes are located exclusively on A-, B
      , or C-locus antigens except for one interlocus epitope. All sera in this study
      were tested in parallel, using single antigen beads that bear either intact or
      dissociated HLA antigens and antibodies with nearly identical specificities were
      identified in all tested sera. Because the specificities of these naturally
      occurring antibodies are unavoidably detected when testing for specificities of
      alloantibodies, it may be necessary to clearly differentiate the two forms of
      antibody. To date, the relevance of these antibodies in transplantation is
      unknown, but even if they are determined to be irrelevant to graft rejection,
      awareness of the newly identified epitopes could prove useful in avoiding the
      unnecessary exclusion of potential transplant donors.

PMID- 19580838
TI  - Safety evaluation of a high-lipid algal biomass from Chlorella protothecoides.
AB  - Chlorella are traditionally freshwater green algae that have been evaluated for
      dietary purposes because of their nutritional value. This study investigates the
      safety of Chlorella protothecoides in a 28-day study. Sprague-Dawley rats were
      administered 0 (control), 2.5, 5.0, or 10% of their diet for 28days using an FDA
      Redbook protocol. The average daily dietary intake of algal biomass was
      determined to be 0, 1794, 3667, and 7557 mg/kg body weight for males and 0, 1867,
      3918, and 8068 mg/kg body weight for females. Hematological and biochemical
      analyses were conducted, and upon completion, gross and microscopic evaluations
      were performed. No signs of toxicity were observed. Although statistically
      significant alterations were noted in several parameters among males and females,
      these changes were deemed to be of no toxicological significance due to the lack
      of dose-response relationships, the fact that they occurred in only one sex, and
      the lack of any supporting gross or microscopic alterations. The no-observed
      adverse-effect level for the algal biomass under the conditions of this study was
      considered to be 10% in the diet, the highest dose tested.

PMID- 19580839
TI  - Endocannabinoids mediate anxiolytic-like effect of acetaminophen via CB1
      receptors.
AB  - Acetaminophen (Paracetamol), a most commonly used antipyretic/analgesic agent, is
      metabolized to AM404 (N-arachidonoylphenolamine) that inhibits uptake and
      degradation of anandamide which is reported to mediate the analgesic action of
      acetaminophen via CB1 receptor. AM404 and anandamide are also reported to produce
      anxiolytic-like behavior. In view of the implication of endocannabinoids in the
      effect of acetaminophen, we contemplated that acetaminophen may have anxiolytic
      like effect. Therefore, this possibility was tested by observing the effects of
      various doses of acetaminophen in mice on anxiety-related indices of Vogel
      conflict test and social interaction test. The results from both the tests
      indicated that acetaminophen (50, 100, or 200 mg/kg, i.p.) or anandamide (10 or
      20 microg/mouse, i.c.v.) dose dependently elicited anxiolytic-like effect, that
      was comparable to diazepam (2 mg/kg, i.p.). Moreover, co-administration of sub
      effective dose of acetaminophen (25 mg/kg, i.p.) and anandamide (5 microg/mouse,
      i.c.v) produced similar anxiolytic effect. Further, pre-treatment with AM251 (a
      CB1 receptor antagonist; 1 mg/kg, i.p.) antagonized the effects of acetaminophen
      and anandamide with no per se effect at 1 mg/kg dose, while anxiogenic effect was
      evident at a higher dose (5 mg/kg, i.p.). None of the treatment/s was found to
      induce any antinociceptive or locomotor impairment effects. In conclusion, the
      findings suggested that acetaminophen (50, 100, or 200 mg/kg, i.p.) exhibited
      dose dependent anxiolytic effect in mice and probably involved endocannabinoid
      mediated mechanism in its effect.

PMID- 19580840
TI  - Potentially fatal interaction between colchicine and disulfiram.

PMID- 19580841
TI  - Induction of cells differentiation and ABC transporters expression by a myco
      estrogen, zearalenone, in human choriocarcinoma cell line (BeWo).
AB  - The mycotoxin zearalenone, produced by Fusarium species, is a worldwide
      contaminant of concern in cereals and other plant products. Due to its estrogenic
      activity, zearalenone (ZEA) is known to have toxicological effect in animals on
      reproductive system and the placental transfer of ZEA was suggested by in vivo
      studies. Although passive diffusion is the principal transport mechanism across
      the placenta, several carrier-mediated transport protein such as ABC transporter
      (P-gp, MRP1, MRP2, BCRP) have been identified in the placenta. In this work, we
      have investigated the effect of ZEA on trophoblast differentiation and ABC
      transporter expression by using an in vitro model of transplacental barrier, the
      BeWo cell line. In the presence of 10 microM ZEA morphological (syncytium
      formation) and biochemical (hCG secretion) differentiation of BeWo cells were
      observed after a 48h exposure. Results were compared to 17beta-estradiol (E2) and
      an inducer of syncytialisation (forskolin). The influence of cell differentiation
      and ZEA exposure on expression profiles of major ABC transporters was
      investigated in BeWo cells: expression of mRNA MRP1, MRP2 and BCRP was induced
      after 24h of ZEA exposure. Induction of P-gp, MRP1, and MRP2 protein was observed
      after 48h of ZEA exposure. Similar results were obtained after forskolin
      exposure. Our study reported for the first time the implication of a food
      contaminant in biological effect and ABC transporter expression modulation in
      human choriocarcinoma cells.

PMID- 19580843
TI  - Affective modulation of conditioned eyeblinks.
AB  - Affective states are known to modulate reflexive actions. Aversive states
      potentiate defensive reflexes while appetitive states diminish them. The present
      study examined whether the same holds for associatively learned defensive
      eyeblinks to mild, initially neutral auditory stimuli. First, delay eyeblink
      conditioning was applied to human participants while they viewed emotionally
      neutral images. Next, the conditioned eyeblink responses (CRs) of the
      participants were tested during the viewing of unpleasant, neutral, or pleasant
      images. The most vigorous CRs were found during the unpleasant images, although
      they did not differ between neutral and pleasant images. The results add to the
      motivational priming hypothesis by demonstrating its partial applicability to
      associatively learned defensive behaviour.

PMID- 19580842
TI  - HIV-1 integrase-hydrolyzing antibodies from sera of HIV-infected patients.
AB  - Autoantibodies with enzymic activities (abzymes) are a distinctive feature of
      autoimmune diseases. It was interesting whether Abs from patients with viral
      diseases can hydrolyze viral proteins. Electrophoretically and immunologically
      homogeneous IgGs were isolated from sera of AIDS patients by chromatography on
      several affinity sorbents. We present evidence showing that 89.5% IgGs purified
      from the sera of HIV-infected patients using several affinity resins including
      Sepharose with immobilized integrase specifically hydrolyze only HIV integrase
      (IN) but not many other tested proteins. Several rigid criteria have been applied
      to show that the IN-hydrolyzing activity is an intrinsic property of AIDS IgGs
      but not from healthy donors. Similar to autoimmune proteolytic abzymes, IN
      hydrolyzing IgGs from some patients were inhibited by specific inhibitors of
      serine and metal-dependent proteases but a significant inhibition of the activity
      by specific inhibitors of acidic- and thiol-like proteases was observed for the
      first time. Although HIV infection leads to formation of Abs to many viral and
      human antigens, no possible biological role for most of them is known. Since anti
      IN IgG can efficiently hydrolyze IN, a positive role of abzymes in counteracting
      the infection cannot be excluded. In addition, detection of IN-hydrolyzing
      activity can be useful for diagnostic purposes and for estimation of the immune
      status in AIDS patients.

PMID- 19580844
TI  - Analysis of NK cell/DC interaction in NK-type lymphoproliferative disease of
      granular lymphocytes (LDGL): role of DNAM-1 and NKp30.
AB  - OBJECTIVE: Natural killer (NK) cells and dendritic cells (DC) can give rise to
      reciprocal functional interactions resulting in promotion of DC maturation,
      killing of immature DC (iDC), and proliferation of NK cells. In this study, we
      analyze whether, in NK-lymphoproliferative disease of granular lymphocytes (LDGL)
      patients, this function could be altered and contribute to the persistence of the
      disease. MATERIALS AND METHODS: Freshly isolated peripheral blood NK granular
      lymphocytes (GL) and NK cell lines derived from 13 different NK-LDGL patients
      were analyzed in coculture experiments to evaluate their ability to interact with
      monocyte-derived DCs (Mo-DC). RESULTS: As compared to NK cells isolated from
      healthy donors, NK-GLs displayed, in most cases, a reduced capability of
      promoting Mo-DC maturation and of killing iDC. These findings could be explained,
      at least in part, by the low expression levels of NKp30: an activating receptor
      involved in the molecular interactions occurring between NK cells and DC. We also
      show that, in the presence of DC-derived cytokines such as interleukin-12, in
      both patients and healthy individuals, DNAM-1 can cooperate with NKp30 to induce
      NK cells to kill DC, release tumor necrosis factor-alpha, and promote DC
      maturation. This contribution, however, is not sufficient to compensate for the
      defect in patients' NK cells. CONCLUSION: Besides expanding knowledge of the
      molecular basis of the NK/DC cross-talk, our study demonstrates that NK cells
      from NK-LDGL patients are impaired in their ability to interact with Mo-DC. The
      possible relationship between such abnormal NK cell/DC interactions and chronic
      NK cell proliferation are discussed.

PMID- 19580845
TI  - A possible mechanism of processive nucleotide and repeat additions by the
      telomerase.
AB  - Telomerase is a specialized cellular ribonucleoprotein complex that can
      synthesize long stretches of a DNA primer by using an intrinsic RNA template
      sequence. This requires that the telomerase must be able to carry out both
      nucleotide and repeat additions. Here, based on available structures and
      experimental data, a model is presented to describe these two addition
      activities. In the model, the forward movement of the polymerase active site
      along the template during the processive nucleotide addition is rectified through
      the incorporation of a matched base, via the Brownian ratchet mechanism. The
      unpairing of the DNA:RNA hybrid and then repositioning of product 3'-end after
      each round of repeat synthesis, which are prerequisites for the processive repeat
      addition, are caused by a force acting on the primer. The force results from the
      conformational transition of the stem III pseudoknot, which is mechanically
      induced by the rotation of TERT fingers together with stem IV loop towards the
      polymerase active site upon a nucleotide binding. Based on the model, the
      dynamics of processive nucleotide and repeat additions by recombinant Tetrahymena
      telomerase is studied analytically, which gives good quantitative explanations to
      the previous experimental results. Moreover, some predicted results are
      presented. In particular, it is shown that the repeat addition processivity is
      mainly determined by the difference between the free-energy change required to
      disrupt the DNA:RNA hybrid and that required to unfold the stem III pseudoknot. A
      large difference in free energy corresponds to a low repeat addition processivity
      while a small difference in free energy corresponds to a high repeat addition
      processivity.

PMID- 19580846
TI  - Analyses of non-leucine-rich repeat (non-LRR) regions intervening between LRRs in
      proteins.
AB  - BACKGROUND: Many proteins have LRR (leucine-rich repeat) units interrupted by non
      LRRs which we call IR (non-LRR island region). METHODS: We identified proteins
      containing LRR@IRs (LRRs having IR) by using a new method and then analyzed their
      natures and distributions. RESULTS: LRR@IR proteins were found in over two
      hundred proteins from prokaryotes and from eukaryotes. These are divided into
      twenty-one different protein families. The IRs occur one to four times in LRR
      regions and range in length from 5 to 11,265 residues. The IR lengths in Fungi
      adenylate cyclases (acys) range from 5 to 116 residues; there are 22 LRR repeats.
      The IRs in Leishmania proteophosphoglycans (ppgs) vary from 105 to 11,265
      residues. These results indicate that the IRs evolved rapidly. A group of LRR@IR
      proteins-LRRC17, chondroadherin-like protein, ppgs, and four Pseudomonas proteins
      have a super motif consisting of an LRR block and its adjacent LRR@IR region.
      This indicates that the entire super motif experienced duplication. The sequence
      analysis of IRs offers functional similarity in some LRR@IR protein families.
      GENERAL SIGNIFICANCE: This study suggests that various IRs and super motifs
      provide a great variety of structures and functions for LRRs.

PMID- 19580847
TI  - Vagal afferent innervation and remodeling in the aortic arch of young-adult
      fischer 344 rats following chronic intermittent hypoxia.
AB  - Previously, we have shown that chronic intermittent hypoxia (CIH) impairs
      baroreflex control of heart rate and augments aortic baroreceptor afferent
      function. In the present study, we examined whether CIH induces structural
      changes of aortic afferent axons and terminals. Young-adult Fischer 344 (F344, 4
      months old) rats were exposed to room air (RA) or CIH for 35-45 days. After 14-24
      days of exposure, they received tracer DiI injection into the left nodose
      ganglion to anterogradely label vagal afferent nerves. After surgery, animals
      were returned to their cages to continue RA or CIH exposure. Twenty-one days
      after DiI injection, the animals were sacrificed and the aortic arch was examined
      using confocal microscopy. In both RA and CIH rats, we found that DiI-labeled
      vagal afferent axons entered the wall of the aortic arch, then fanned out and
      branched into large receptive fields with numerous terminals (flower-sprays, end
      nets and free endings). Vagal afferent axons projected much more to the anterior
      wall than to the posterior wall. In general, the flower-sprays, end-nets and free
      endings were widely and similarly distributed in the aortic arch of both groups.
      However, several salient differences between RA and CIH rats were found. Compared
      to RA control, CIH rats appeared to have larger vagal afferent receptive fields.
      The CIH rats had many abnormal flower-sprays, end-nets, and free endings which
      were intermingled and diffused into "bush-like" structures. However, the total
      number of flower-sprays was comparable (P>0.05). Since there was a large variance
      of the size of flower-sprays, we only sampled the 10 largest flower-sprays from
      each animal. CIH substantially increased the size of large flower-sprays
      (P<0.01). Numerous free endings with enlarged varicosities were identified,
      resembling axonal sprouting structures. Taken together, our data indicate that
      CIH induces significant remodeling of afferent terminal structures in the aortic
      arch of F344 rats. We suggest that such an enlargement of vagal afferent
      terminals may contribute to altered aortic baroreceptor function following CIH.

PMID- 19580848
TI  - Cocaine regulates ezrin-radixin-moesin proteins and RhoA signaling in the nucleus
      accumbens.
AB  - The ezrin-radixin-moesin (ERM) proteins are a family of widely distributed
      membrane-associated proteins and have been implicated not only in cell-shape
      determination but also in signaling pathway. The nucleus accumbens (NAcc) is an
      important neuronal substrate mediating the effects of drugs of abuse. However, it
      has not been determined yet how ERM proteins are regulated in this site by drugs
      of abuse. Here we show in rat that the phosphorylation levels of ERM protein are
      dose- and time-dependently decreased in the NAcc by a single injection of cocaine
      (15 or 30 mg/kg i.p.). Further, we show that the amount of active RhoA, a small
      GTPase protein, is significantly reduced in the NAcc by cocaine, while the
      phosphorylation levels of ERM protein are also decreased by bilateral
      microinjections in this site of the Rho kinase inhibitors. Together, these
      results suggest that cocaine reduces phosphorylated ERM levels in the NAcc by
      making downregulation of RhoA-Rho kinase signaling, which may importantly
      contribute to initiate synaptic changes in this site leading to drug addiction.

PMID- 19580850
TI  - Induction of heat shock protein 70 reduces the alteration of striatal electrical
      activity caused by mitochondrial impairment.
AB  - Since mild thermal stress seems to exert neuroprotection via induction of heat
      shock protein 70 kDa (hsp70), we tested whether hsp70 would preserve striatal
      bioelectrical activity under conditions of mitochondrial impairment.
      Corticostriatal slices from rats that had undergone mild thermal stress were
      exposed to either rotenone or 3-nitropropionic acid (3-NP), that selectively
      inhibits mitochondrial complex I and complex II, respectively. Rotenone is
      utilized to obtain an experimental model of Parkinson's disease while 3-NP
      replicates Huntington's disease phenotype in experimental animals. The cerebral
      hsp70 increase did not alter field potential amplitude of the slices but
      partially protected them against rotenone-induced neurotoxicity. Similarly,
      induction of hsp70 had also a partial neuroprotective effect on the neurotoxicity
      caused by 3-NP on striatal field potential. Since rotenone and 3-NP treatments
      mimic the mitochondrial impairment and oxidative stress that contribute to
      development of Parkinson's disease and Huntington's disease, these data suggest
      that induction of hsp70 might represent a possible neuroprotective mechanism
      against the pathophysiological chain of events implicated in these
      neurodegenerative disorders.

PMID- 19580849
TI  - Social and physical environment alter cocaine conditioned place preference and
      dopaminergic markers in adolescent male rats.
AB  - This study was done to determine whether social and environmental factors alter
      cocaine reward and proteins implicated in mediating drug reward in rats during
      early adolescence. On postnatal day (PND) 23, rats were housed under conditions
      where both social (number of rats per cage) and environmental (availability of
      toys) factors were manipulated. Socially isolated rats were housed alone
      impoverished with no toys (II) or enriched with toys (IE). Social rats were
      housed two rats/cage with no toys (SI2) or with toys (SE2), or three/cage with
      (SE3) or without (SI3) toys. On PND 43, cocaine conditioned place preference
      (CPP) sessions began with the post-test done on PND 47. Cocaine CPP was
      established in response to 5 or 10 mg/kg cocaine in II rats, and CPP was
      decreased with the addition of cage mates or toys. No CPP was seen to any dose in
      SI3 or SE3 rats. Enriched housing (SE3) increased dopamine transporter (DAT)
      protein in the nucleus accumbens compared to II. There also were differential
      effects of cocaine on tyrosine hydroxylase and DAT depending on housing, with
      both increased by cocaine in II but not SE3 rats. DARPP-32 was unchanged by
      housing or cocaine, while phospho-Thr(34)-DARPP-32 was increased by cocaine
      treatment across conditions. Thus, both social and environmental enrichment
      decrease cocaine CPP during adolescence and different housing alters proteins
      that regulate dopaminergic neurotransmission in a manner that may account for the
      observed differences in cocaine-induced reward.

PMID- 19580851
TI  - Activation of the septohippocampal system differentiates anxiety from fear in
      startle paradigms.
AB  - It has been suggested that different brain areas are involved in the modulation
      and expression of fear and anxiety. In the present study we investigated these
      potential differences by using the fear-potentiated-startle (FPS) and light
      enhanced-startle (LES) paradigms to differentiate between fear and anxiety,
      respectively. Male Wistar rats were tested in the FPS and LES paradigm and
      perfused 1 h after the test session. Fos immunoreactivity (IR) was quantified in
      21 brain areas and compared between FPS, LES and four control conditions. Both
      FPS and LES procedures significantly enhanced the acoustic startle response. A
      principal component analysis of Fos-IR-data showed that 70% of the changes in Fos
      IR could be explained by three independent components: an arousal-component,
      identifying brain areas known to be activated under conditions of vigilance,
      arousal and stress, a LES- and an FPS-component. The LES component comprised the
      septohippocampal system and functionally interrelated areas including nucleus
      accumbens, anterior cingulate cortex, lateral habenula and supramammillary areas,
      but not the dorsolateral part of the bed nucleus of the stria terminalis. The
      central amygdaloid nucleus and the dorsolateral part of the bed nucleus of the
      stria terminalis loaded exclusively on the FPS component. Analysis of the
      separate brain areas revealed significantly higher Fos-IR in LES relative to FPS
      in the anterior cingulate cortex, nucleus accumbens shell, lateral septum,
      lateral habenula and area postrema. We conclude that the neural circuitry
      activated during FPS and LES shows clear differences. In anxiety as induced by
      LES, activation of the septohippocampal system and related areas seems to play a
      major role. In fear as induced by FPS, the central amygdaloid nucleus and the
      dorsolateral part of the bed nucleus of the stria terminalis loaded on the same
      component, but Fos-IR observed in these brain regions did not differentiate
      between anxiety and fear. Furthermore, principal-component analysis appears a
      useful tool in detecting and describing correlated changes in patterns of
      neuronal activity.

PMID- 19580853
TI  - Acute tryptophan depletion in rats alters the relationship between cerebral blood
      flow and glucose metabolism independent of central serotonin.
AB  - Acute tryptophan depletion (ATD) decreases the 5-HT precursor tryptophan (TRP) in
      blood and is used both clinically and preclinically to investigate the
      involvement of 5-HT in the development of depressive symptomatology. Depression
      is associated with both central 5-HT dysfunction and abnormalities in the normal
      relationship between regional cerebral blood flow (CBF) and glucose metabolism
      (CMRG). In this study, ATD was applied in Wistar rats to investigate the
      cerebrovascular effects of acute changes in peripheral TRP. Rats were orally fed
      with a protein-carbohydrate mixture, either containing or lacking TRP. Four hours
      later, CBF or CMRG was measured by quantitative autoradiographic imaging in 43
      brain regions of interest (ROI). In plasma, ATD resulted in a 40% reduction in
      the ratio of TRP to the sum of other large neutral amino acids, but had no
      measurable effect upon TRP or 5-HT levels in hippocampus or prefrontal cortex.
      Nevertheless, ATD significantly reduced local CBF in 11 of the 43 brain ROIs,
      while local CMRG remained unchanged. Global analysis of all 43 ROIs revealed a
      close correlation between CBF and CMRG within both treatment groups. However, the
      overall ratio (=slope) after ATD (m=1.07) was significantly decreased compared to
      the control group (m=1.27), indicating a state of relative cerebral oligaemia.
      Since ATD induced a significant lowering of peripheral TRP, without affecting
      central TRP or 5-HT concentrations, the decrease in CBF and global change in the
      flow-metabolism relationship cannot be directly attributed to decreases in brain
      TRP availability. This could be explained if the raphe were selectively
      vulnerable to ATD, but the exact mechanism remains unknown. Nevertheless, these
      data suggest that cerebrovascular disturbances should be considered as a
      potential contributory factor in studies of serotonergic dysfunction, including
      depression, with important implications for imaging studies that use CBF alone as
      a measure of neuronal function.

PMID- 19580854
TI  - Immunohistochemical localisation of the creatine transporter in the rat brain.
AB  - Creatine (Cr) is required to maintain ATP levels in the brain. The transport of
      Cr across the blood-brain barrier and into neurones requires a specific creatine
      transporter (CRT). Mutations in the CRT gene (SLC6A8) result in a novel form of X
      linked mental retardation, characterised by developmental delays, seizures and a
      complete absence of Cr from the brain. To identify cell types and regions that
      depend on Cr for energy metabolism we have determined the regional and cellular
      localisation of CRT protein in the rat brain using immunohistochemical techniques
      with a highly specific, affinity-purified, CRT antibody. The results show high
      levels of CRT localisation is associated with specific brain regions and certain
      cell types. The CRT is predominantly found in neurones. CRT immunoreactivity is
      particularly abundant in the olfactory bulb, granule cells of the dentate gyrus
      of the hippocampus, pyramidal neurones of the cerebral cortex, Purkinje cells of
      the cerebellum, motor and sensory cranial nerve nuclei in the brainstem and the
      dorsal and ventral horns of the spinal cord. Low levels of CRT were seen in the
      basal ganglia and white matter. Overall, CRT was found to show high intensities
      of labelling in the major motor and sensory regions of the forebrain, brainstem
      and spinal cord and forebrain regions associated with learning, memory and limbic
      functions. It is hypothesised that regions with high CRT expression are likely to
      have high metabolic ATP requirements and that areas with low CRT levels are those
      regions which are particularly vulnerable in neurodegenerative diseases.

PMID- 19580852
TI  - Protein kinase Calpha mediates a novel form of plasticity in the accessory
      olfactory bulb.
AB  - Modification of synapses in the accessory olfactory bulb (AOB) is believed to
      underlie pheromonal memory that enables mate recognition in mice. The memory,
      which is acquired with single-trial learning, forms only with coincident
      noradrenergic and glutamatergic inputs to the AOB. The mechanisms by which
      glutamate and norepinephrine (NE) alter the AOB synapses are not well understood.
      Here we present results that not only reconcile the earlier, seemingly
      contradictory, observations on the role of glutamate and NE in changing the AOB
      synapses, but also reveal novel mechanisms of plasticity. Our studies suggest
      that initially, glutamate acting at Group II metabotropic receptors and NE acting
      at alpha(2)-adrenergic receptors inhibit N-type and R-type Ca(2+) channels in
      mitral cells via a G-protein. The N-type and R-type Ca(2+) channel inhibition is
      reversed by activation of alpha(1)-adrenergic receptors and protein kinase Calpha
      (PKCalpha). Based on these results, we propose a hypothetical model for a new
      kind of synaptic plasticity in the AOB that accounts for the previous behavioral
      data on pheromonal memory. According to this model, initial inhibition of the
      Ca(2+) channels suppresses the GABAergic inhibitory feedback to mitral cells,
      causing disinhibition and Ca(2+) influx. NE also activates phospholipase C (PLC)
      through alpha(1)-adrenergic receptors generating inositol 1,4,5-trisphosphate and
      diacylglycerol (DAG). Calcium and DAG together activate PKCalpha which switches
      the disinhibition to increased inhibition of mitral cells. Thus, PKCalpha is
      likely to be a coincidence detector integrating glutamate and NE input in the AOB
      and bridging the short-term signaling to long-term structural changes resulting
      in enhanced inhibition of mitral cells that is thought to underlie memory
      formation.

PMID- 19580855
TI  - Optimization of melt pelletization in a high shear mixer.
AB  - The effects of process conditions and binder content on the process yield and
      pellet characteristics of two formulations prepared by melt pelletization in a
      laboratory-type high shear mixer were investigated. The formulations were
      prepared using Gelucire 50/13 and Lutrol F68 as meltable binders. The factors
      under investigation were impeller speed, mixing time, mixer load, binder
      concentration, and their reciprocal interactions. Analysis of variance (ANOVA)
      was used in order to study the significance of above mentioned process variables
      on the useful yield. Twenty-seven experiments were required for the response
      surface methodology based on Box-Behnken experimental design (24 combinations
      with three replications of the centre point) for each formulation. The control
      over the process and the quality of the resulting pellets were found to depend on
      the rheological properties of the binders used. In the case of a low viscosity
      binder (Gelucire 50/13), the process was easily controllable whereas in the case
      of a high viscosity binder (Lutrol F68), the process was more difficult to
      control. The useful yield of the formulation in the case of the low viscosity
      binder was found to be mostly influenced by the concentration of the binder. On
      the other hand, different binder concentrations did not affect the useful yield
      of the formulation prepared by use of the high viscosity binder. In the latter
      case, mixing time was identified as the variable that mostly influenced the
      pelletization process. Finally response surface methodology was applied to find
      the optimum values of the process variables.

PMID- 19580856
TI  - Wheat germ agglutinin-conjugated chitosan-Ca-alginate microparticles for local
      colon delivery of 5-FU: development and in vitro characterization.
AB  - The aim of this work was to prepare lectin-conjugated chitosan-Ca-alginate
      microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5
      FU) for efficient local treatment of colon cancer. MPs were prepared by a novel
      one-step spray-drying technique and after wheat germ agglutinin (WGA)
      conjugation, they were characterized for size, swelling behavior, surface charge,
      entrapment efficiency and in vitro drug release. Prepared particles were
      spherical, with 6.73 microg/mg of WGA conjugated onto their surface. The size and
      zeta potential increased after conjugation, from 6.6 to 14.7 microm and from 9.6
      to 15.3 mV, while drug encapsulation was 75.6 and 72.8%, respectively after
      conjugation. The swelling behavior of beads was mainly determined by properties
      of the cross-linked chitosan-alginate network. In vitro drug release studies
      carried out in simulated in vivo conditions with respect to pH, confirmed the
      potential of the particles to release the drug in a controlled manner. Also, the
      drug release was not significantly affected by WGA conjugation. The retention of
      biorecognitive activity of WGA after covalent coupling to MPs was confirmed by
      haemagglutination test. Functionalized MPs showed excessive mucoadhesiveness in
      vitro, due to the positive surface charge, pH-dependent swelling of the matrix
      and lectin-sugar recognition.

PMID- 19580857
TI  - Antiviral efficacy against hepatitis B virus replication of oleuropein isolated
      from Jasminum officinale L. var. grandiflorum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum officinale L. var. grandiflorum (JOG) is
      a folk medicine used for the treatment of hepatitis in south of China.
      Phytochemical studies showed that secoiridoid glycosides are the typical
      constituents of this plant. AIM OF THE STUDY: The present study was undertaken to
      evaluate the effect of oleuropein (Ole) derived from the flowers of JOG on
      hepatitis B virus (HBV) replication in HepG2 2.2.15 cell line in vitro and duck
      hepatitis B virus (DHBV) replication in ducklings in vivo. MATERIAL AND METHODS:
      The extracellular hepatitis B e antigen (HBeAg) and hepatitis B surface antigen
      (HBsAg) concentrations in cell culture medium were determined by ELISA. DHBV in
      duck serum was analyzed by dot blot. RESULTS: Ole blocks effectively HBsAg
      secretion in HepG2 2.2.15 cells in a dose-dependent manner (IC(50)=23.2
      microg/ml). Ole (80 mg/kg, intraperitoneally, twice daily) also reduced viremia
      in DHBV-infected ducks. CONCLUSION: Ole therefore warrants further investigation
      as a potential therapeutic agent for HBV infection.

PMID- 19580858
TI  - Antinociceptive activity of coniine in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hemlock was used as an analgesic in certain
      ethnopharmacological traditions and there has been no record about the
      antinociceptive effect of coniine which is the major alkaloid compound of
      Hemlock. AIM OF THIS STUDY: The present study was undertaken to evaluate the
      possible antinociceptive activity of coniine. MATERIAL AND METHODS:
      Antinociceptive activity of coniine was tested dose in Hotplate test (thermal
      pain model) and in Writhing test (chemical pain model) in different nociception
      models. RESULTS: Coniine caused a prolongation in reaction time in Hotplate test
      at 20mg/kg dose. In addition, it was observed that coniine decreased the number
      of writhes in Writhing test. Both data indicated an antinociceptive effect of
      coniine. A rotarod test was also conducted in order to clarify, whether this
      activity was related with a loss of locomotion or with an analgesic activity.
      None of the chemical agents at those doses used in experiments caused a loss of
      locomotor activity. It was also shown that antinociceptive effect of morphine was
      potentialized by coniine which was inhibited by nicotinic receptor blocker
      mecamylamine (1mg/kg). CONCLUSION: Coniine has antinociceptive effect via the
      nicotinic receptors. A pharmacological assessment about the painless death of
      Socrates due to Hemlock (coniine) toxicity has also been presented by using this
      data.

PMID- 19580859
TI  - Qingkailing injection attenuates apoptosis and neurologic deficits in a rat model
      of intracerebral hemorrhage.
AB  - AIM OF THE STUDY: Traditional Chinese herb Angong Niuhuang Pill (AGNHP) is a
      famous preparation for neurological diseases; Qingkailing injection (QKL), an
      extract of AGNHP has similar clinical applications. This investigation was
      designed to further elucidate the neuroprotective effect of QKL on intracerebral
      hemorrhage (ICH). MATERIALS AND METHODS: ICH was produced in adult Sprague-Dawley
      rats by injection of collagenase IV. Three incremental doses of QKL injection
      including low-(0.5 ml/kg), moderate-(1 ml/kg) and high-dosage (2 ml/kg) were
      administered twice, 3 and 12h following ICH. TUNEL and caspase-3 activity were
      measured at 1d after ICH, and apomorphine-induced rotation was evaluated at 1d,
      7d, 14 d and 28 d. RESULTS: Administration of high-dose QKL inhibited TUNEL
      positive cells (p<0.05) and caspase-3 activity (p<0.05) at 1d following ICH, and
      reduced apomorphine-induced rotation at 1d (p<0.01), 7d, 14 d and 28 d (p<0.05),
      compared with the controls. However, QKL in a low or moderate dose had no such
      effect. CONCLUSION: QKL reduced brain damage of intracerebral hemorrhage through
      inhibiting apoptosis, which suggested a potential intervention for ICH patients.

PMID- 19580860
TI  - Does dietary restriction reduce life span in male fruit-feeding butterflies?
AB  - Male life history and resource allocation is not frequently studied in aging and
      life span research. Here, we verify that males of long-lived fruit-feeding
      butterfly species have reduced longevity on restricted diets [Beck, J., 2007. The
      importance of amino acids in the adult diet of male tropical rainforest
      butterflies. Oecologia 151, 741-747], in contrast to the common finding of
      longevity extension in dietary restriction experiments in Drosophila and some
      other organisms. Males of some of the most long-lived species of fruit-feeding
      butterflies were collected from Kibale Forest, Uganda, and kept on diets of
      either sugar or mashed banana. Seven out of eight species had non-significantly
      longer life spans on mashed banana diets. Data analysis using a time-varying Cox
      model with species as covariate showed that males had reduced survival on the
      sugar diet during the first 35 days of captive life, but the effect was absent or
      reversed at more advanced ages. These results challenge the generality of dietary
      restriction as a way to extend life span in animals. We argue that such studies
      on males are promising tools for better understanding life history evolution and
      aging because males display a wider variety of tactics for obtaining reproductive
      success than females.

PMID- 19580862
TI  - Prolonged exposure to ketamine increases neurodegeneration in the developing
      monkey brain.
AB  - Ketamine, a widely used pediatric anesthetic, has been associated with enhanced
      neuronal toxicity in the developing brain, but mechanisms and neuronal
      susceptibility to neurotoxic insult leading to neuronal cell death remain poorly
      defined. One of the main goals of this study was to determine whether there is a
      duration of ketamine-induced anesthesia below which no significant ketamine
      induced neurodegeneration can be detected. Newborn rhesus monkeys (postnatal day
      5 or 6) were administered ketamine intravenously for 3, 9 or 24h to maintain a
      steady anesthetic plane, followed by a 6-h withdrawal period. The 9- and 24-h
      durations were selected as relatively long and extremely long exposures,
      respectively, while the 3-h treatment more closely approximates a typical
      duration of pediatric general anesthesia. Animals were subsequently perfused
      under anesthesia and brain tissue was processed for analyses using silver and
      Fluoro-Jade C stains and caspase-3 immunostain. The results indicated that no
      significant neurotoxic effects occurred if the anesthesia duration was 3h.
      However, ketamine infusions for either 9 or 24h significantly increased neuronal
      cell death in layers II and III of the frontal cortex. Although a few caspase-3-
      and Fluoro-Jade C-positive neuronal profiles were observed in some additional
      brain areas including the hippocampus, thalamus, striatum and amygdala, no
      significant differences were detected between ketamine-treated and control
      monkeys in these areas after 3, 9 or 24h of exposure. These data show that
      treatment with ketamine up to 3h is without adverse effects as determined by
      nerve cell death. However, anesthetic durations of 9h or greater are associated
      with significant brain cell death in the frontal cortex. Thus, the threshold
      duration below which no neurotoxicity would be expected is somewhere between 3
      and 9h.

PMID- 19580863
TI  - Role of IL-1 beta and COX2 in silica-induced IL-6 release and loss of pneumocytes
      in co-cultures.
AB  - The pro-inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 are of great
      importance in the development of silica-induced lung damage and repair. In this
      study we investigated the role of IL-1 beta, TNF-alpha and COX2 in silica-induced
      regulation of IL-6 release and pneumocyte loss in various mono- and co-cultures
      of monocytes, pneumocytes and endothelial cells. All co-cultures with monocytes,
      and especially cultures including endothelial cells, showed an increase of silica
      induced release of IL-6 compared to the respective monocultures. Treatment with
      the antagonist IL-1 ra strongly decreased IL-1 beta and IL-6 release in contact
      co-cultures of monocytes and pneumocytes. COX2 up-regulation by silica and IL-1
      beta was eliminated by IL-1 ra. Inhibition of COX2 markedly reduced both IL-1
      beta and IL-6 release. IL-1 ra was more effective than COX2-inhibition in
      reduction of IL-6, but not of IL-1 beta. Silica-induced pneumocyte loss was
      reduced by IL-1 beta, but this effect was not counteracted by the IL-1 receptor
      antagonist. Our findings suggest that silica-induced IL-6 release from
      pneumocytes is mainly mediated via IL-1 beta release from the monocytes, via both
      COX2-dependent and -independent pathways. Notably, COX2-derived mediators seem
      crucial for a positive feed-back regulation of IL-1 beta release from the
      monocytes. In contrast to silica-induced IL-6, the reduction in pneumocyte loss
      by IL-1 beta does not seem to be regulated through an IL-1R1-dependent mechanism.

PMID- 19580861
TI  - Multiple mild heat-shocks decrease the Gompertz component of mortality in
      Caenorhabditis elegans.
AB  - Exposure to mild heat-stress (heat-shock) can significantly increase the life
      expectancy of the nematode Caenorhabditis elegans. A single heat-shock early in
      life extends longevity by 20% or more and affects life-long mortality by
      decreasing initial mortality only; the rate of increase in subsequent mortality
      (Gompertz component) is unchanged. Repeated mild heat-shocks throughout life have
      a larger effect on life span than does a single heat-shock early in life. Here,
      we ask how multiple heat-shocks affect the mortality trajectory in nematodes and
      find increases of life expectancy of close to 50% and of maximum longevity as
      well. We examined mortality using large numbers of animals and found that
      multiple heat-shocks not only decrease initial mortality, but also slow the
      Gompertz rate of increase in mortality. Thus, multiple heat-shocks have anti
      aging hormetic effects and represent an effective approach for modulating aging.

PMID- 19580865
TI  - Self-assembly and function of primitive cell membranes.
AB  - We describe possible pathways for separating amphiphilic molecules from organic
      material on the early earth to form membrane-bound structures required for the
      start of cellular life. We review properties of the first membranes and their
      function as permeability barriers. Finally, we discuss the emergence of protein
      mediated ion transport across membranes, which facilitated many other cellular
      functions.

PMID- 19580864
TI  - Diverse aadA gene cassettes on class 1 integrons introduced into soil via spread
      manure.
AB  - Class 1 integrons are assumed to play an important role in dissemination of
      antibiotic resistance genes. Class 1 integrons from clinical isolates often have
      5'- and 3'-conserved segments flanking the variable region where gene cassettes
      integrate. Primers targeting the conserved segments were used to amplify the
      variable region from total community DNA of manure and soil. Integron gene
      cassette diversity in manure and manured soils was studied by cloning,
      restriction fragment length polymorphism (RFLP) analysis and sequencing. The
      analyzed group of integrons could be detected in manured soils but not in soil
      without a history of manure treatment. aadA gene cassettes encoding resistance to
      streptomycin and spectinomycin were frequently detected in the clone libraries.
      To elucidate whether "clinical" class 1 integron gene cassettes are typically
      introduced via manure into agricultural soil, a survey with a unique set of
      manure samples originating from 15 different pig-producing facilities was
      performed. aadA gene cassettes were detected in all field-scale manures,
      confirming that aadA genes localized on class 1 integrons are introduced via
      piggery manure into agricultural soils. In addition, class 1 integrons without
      gene cassettes were detected in total community DNA of many manures.

PMID- 19580866
TI  - betaFTZ-F1 and Broad-Complex positively regulate the transcription of the wing
      cuticle protein gene, BMWCP5, in wing discs of Bombyx mori.
AB  - The present study was undertaken to clarify the mechanism regulating cuticle
      protein gene expression. Expression of BMWCP5 was strong at around pupation and
      weak at the mid-pupal stage in wing tissues of Bombyx mori. We analyzed the
      upstream region of the BMWCP5 gene using a transient reporter assay with a gene
      gun system to identify the regulatory elements responsible for its unique
      expression pattern. We identified two betaFTZ-F1 binding sites to be important
      cis-acting elements for the transcription activation of the luciferase reporter
      gene by an ecdysone pulse. Site-directed mutagenesis of these sites, followed by
      introduction into wing discs, significantly decreased the reporter activity. We
      also found that the regions carrying the binding sites for the ecdysone
      responsive factor BR-C Z4 (BR-Z4) were responsible for the hormonal enhancement
      of the reporter gene activity in wing discs. Mutation of the BR-Z4 binding sites
      decreased the reporter activity. The nuclear proteins that bound to these betaFTZ
      F1 and BR-Z4 sites were identified by an electrophoretic mobility shift assay
      (EMSA). The results demonstrate for the first time that the BR-Z4 isoform can
      bind to the upstream region of the cuticle protein gene, BMWCP5, and activate its
      expression. The results also suggest that the BMWCP5 transcription is primarily
      regulated by the ecdysone pulse through betaFTZ-F1, and the stage-specific
      enhancement is brought about through BR-Z4.

PMID- 19580867
TI  - Activation of BMWCP10 promoter and regulation by BR-C Z2 in wing disc of Bombyx
      mori.
AB  - The cuticle protein gene BMWCP10 is transcriptionally upregulated by ecdysone
      during development. In the present study, using a transient reporter assay, the
      activity of various genomic segments at the 5'-flanking region of the BMWCP10
      gene in driving gene expression and their involvement in ecdysone-mediated
      activation were assessed in the Bombyx wing disc. The promoter activity of
      BMWCP10 was responsive to 20-hydroxyecdysone (20E) in a dose-dependent manner,
      and the highest luciferase activity was observed in the presence of 2 microg/ml
      20E. Furthermore, the upstream BMWCP10 promoter was activated by 20E in a stage
      specific manner, and the 2.9-kb promoter contained essential elements for the
      temporal regulation of BMWCP10 in the Bombyx wing disc. Deletion studies revealed
      that the -598/-387 bp region was required for high-level transcription. In this
      region, a BR-C Z2 binding element was identified by electrophoretic mobility
      shift assay (EMSA). Site-directed mutagenesis of this element in the context of
      the 598-bp promoter fragment significantly decreased the reporter activity in
      response to ecdysone treatment. The results confirmed the role of BmBR-C Z2 in
      the transcription regulation of BMWCP10 and suggested the contribution of BmBR-C
      Z2 to BMWCP10 induction by 20E.

PMID- 19580869
TI  - Soluble expression and characterization of a mouse epididymis-specific protein
      lipocalin6.
AB  - Mouse lipocalin6 (mLcn6) was recently identified to be specifically expressed in
      the epididymis and speculated to may play a role in sperm maturation. However,
      further studies were hindered due to the bottleneck to obtain enough recombinant
      mLcn6 proteins. In this article, GB1 tag was successfully applied to improve the
      soluble expression of mLcn6. Thermal unfolding experiments demonstrate that GB1
      can enhance the structural stability of mLcn6. Fluorescence spectroscopy
      experiments show that mLcn6 prepared according to our procedure has high
      affinities to both retinoic acid (K(d)=810nM) and retinol (K(d)=210nM). In
      conclusion, soluble, stable and active mLcn6 was recombinantly prepared with the
      help of the GB1 tag, which will facilitate the structural and functional studies
      of mLcn6.

PMID- 19580868
TI  - Disorganized olfactory bulb lamination in mice deficient for transcription factor
      AP-2epsilon.
AB  - Within the olfactory bulb, neurons and their axonal connections are organized
      into distinct layers corresponding to different functionalities. Here we
      demonstrate that transcription factor AP-2epsilon is required for olfactory bulb
      development, specifically the establishment of appropriate neuronal lamination.
      During normal mouse embryogenesis, AP-2epsilon transcripts are one of the
      earliest markers of olfactory bulb formation, and expression eventually becomes
      refined to the projection neurons, the mitral and tufted cells. To assess the
      function of AP-2epsilon in olfaction, we generated a null allele (the "AK"
      allele) by inserting a Cre recombinase transgene into the endogenous AP-2epsilon
      genomic locus. AP-2epsilon-null mice exhibited defective olfactory bulb
      architecture. The mitral cell layer was disorganized, typified by misoriented and
      aberrantly positioned projection neurons, and the adjacent internal plexiform
      layer was absent. Despite the significant disruption of olfactory bulb
      organization, AP-2epsilon null mice were viable and could discriminate a variety
      of odors. AP-2epsilon-null mice thus provide compelling evidence for the robust
      nature of the mouse olfactory system, and serve as a model system to probe both
      the regulation of neuronal lamination and the functional circuitry of the
      olfactory bulb. We also show that Cre recombinase expression directed by the AP
      2epsilon locus can specifically target floxed genes within the olfactory bulb,
      extending the utility of this AK allele.

PMID- 19580870
TI  - High-level expression and characterization of Fusarium solani cutinase in Pichia
      pastoris.
AB  - High-level extracellular production of Fusarium solani cutinase was achieved
      using a Pichia pastoris expression system. The cutinase-encoding gene was cloned
      into pPICZalphaA with the Saccharomyces cerevisiae alpha-factor signal sequence
      and methanol-inducible alcohol oxidase promoter by two different ways. The
      additional sequences of the c-myc epitope and (His)6-tag of the vector were fused
      to the C-terminus of cutinase, while the other expression vector was constructed
      without any additional sequence. P. pastoris expressing the non-tagged cutinase
      exhibited about two- and threefold higher values of protein amount and cutinase
      activity in the culture supernatant, respectively. After simple purification by
      diafiltration process, both cutinases were much the same in the specific activity
      and the biochemical properties such as the substrate specificity and the effects
      of temperature and pH. In conclusion, the high-level secretion of F. solani
      cutinase in P. pastoris was demonstrated for the first time and would be a
      promising alternative to many expression systems previously used for the large
      scale production of F. solani cutinase in Saccharomyces cerevisiae as well as
      Escherichia coli.

PMID- 19580871
TI  - Fifty years later: the sequence, structure and function of lacewing cross-beta
      silk.
AB  - Classic studies of protein structure in the 1950s and 1960s demonstrated that
      green lacewing egg stalk silk possesses a rare native cross-beta sheet
      conformation. We have identified and sequenced the silk genes expressed by adult
      females of a green lacewing species. The two encoded silk proteins are 109 and 67
      kDa in size and rich in serine, glycine and alanine. Over 70% of each protein
      sequence consists of highly repetitive regions with 16-residue periodicity. The
      repetitive sequences can be fitted to an elegant cross-beta sheet structural
      model with protein chains folded into regular 8-residue long beta strands. This
      model is supported by wide-angle X-ray scattering data and tensile testing from
      both our work and the original papers. We suggest that the silk proteins assemble
      into stacked beta sheet crystallites bound together by a network of cystine cross
      links. This hierarchical structure gives the lacewing silk high lateral stiffness
      nearly threefold that of silkworm silk, enabling the egg stalks to effectively
      suspend eggs and protect them from predators.

PMID- 19580872
TI  - Crystal structure of the in vivo-assembled Bacillus subtilis Spx/RNA polymerase
      alpha subunit C-terminal domain complex.
AB  - The Bacillus subtilis Spx protein is a global transcription factor that interacts
      with the C-terminal domain of the RNA polymerase alpha subunit (alphaCTD) and
      regulates transcription of genes involved in thiol-oxidative stress, sporulation,
      competence, and organosulfur metabolism. Here we determined the X-ray crystal
      structure of the Spx/alphaCTD complex from an entirely new crystal form than
      previously reported [Newberry, K.J., Nakano, S., Zuber, P., Brennan, R.G., 2005.
      Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional
      regulator, Spx, in complex with the alpha C-terminal domain of RNA polymerase.
      Proc. Natl. Acad. Sci. USA 102, 15839-15844]. Comparison of the previously
      reported sulfate-bound complex and our sulfate-free complex reveals subtle
      conformational changes that may be important for the role of Spx in regulating
      organosulfur metabolism.

PMID- 19580873
TI  - Development, validation, and comparison of ICA-based gradient artifact reduction
      algorithms for simultaneous EEG-spiral in/out and echo-planar fMRI recordings.
AB  - EEG data acquired in an MRI scanner are heavily contaminated by gradient
      artifacts that can significantly compromise signal quality. We developed two new
      methods based on independent component analysis (ICA) for reducing gradient
      artifacts from spiral in-out and echo-planar pulse sequences at 3 T, and compared
      our algorithms with four other commonly used methods: average artifact
      subtraction (Allen, P., Josephs, O., Turner, R., 2000. A method for removing
      imaging artifact from continuous EEG recorded during functional MRI. NeuroImage
      12, 230-239.), principal component analysis (Niazy, R., Beckmann, C., Iannetti,
      G., Brady, J., Smith, S., 2005. Removal of FMRI environment artifacts from EEG
      data using optimal basis sets. NeuroImage 28, 720-737.), Taylor series ( Wan, X.,
      Iwata, K., Riera, J., Kitamura, M., Kawashima, R., 2006. Artifact reduction for
      simultaneous EEG/fMRI recording: adaptive FIR reduction of imaging artifacts.
      Clin. Neurophysiol. 117, 681-692.) and a conventional temporal ICA algorithm.
      Models of gradient artifacts were derived from simulations as well as a water
      phantom and performance of each method was evaluated on datasets constructed
      using visual event-related potentials (ERPs) as well as resting EEG. Our new
      methods recovered ERPs and resting EEG below the beta band (<12.5 Hz) with high
      signal-to-noise ratio (SNR>4). Our algorithms outperformed all of these methods
      on resting EEG in the theta and alpha bands (SNR>4); however, for all methods,
      signal recovery was modest (SNR approximately 1) in the beta band and poor
      (SNR<0.3) in the gamma band and above. We found that the conventional ICA
      algorithm performed poorly with uniformly low SNR (<0.1). Taken together, our new
      ICA-based methods offer a more robust technique for gradient artifact reduction
      when scanning at 3 T using spiral in-out and echo-planar pulse sequences. We
      provide new insights into the strengths and weaknesses of each method using a
      unified subspace framework.

PMID- 19580874
TI  - Time course and functional neuroanatomy of speech segmentation in adults.
AB  - The present investigation was devoted to unraveling the time-course and brain
      regions involved in speech segmentation, which is one of the first processes
      necessary for learning a new language in adults and infants. A specific brain
      electrical pattern resembling the N400 language component was identified as an
      indicator of speech segmentation of candidate words. This N400 trace was clearly
      elicited after a short exposure to the words of the new language and showed a
      decrease in amplitude with longer exposure. Two brain regions were observed to be
      active during this process: the posterior superior temporal gyrus and the
      superior part of the ventral premotor cortex. We interpret these findings as
      evidence for the existence of an auditory-motor interface that is responsible for
      isolating possible candidate words when learning a new language in adults.

PMID- 19580875
TI  - Linearity of blood-oxygenation-level dependent signal at microvasculature.
AB  - The relationship between the blood-oxygenation-level dependent (BOLD) signal and
      its underlying neuronal activity is still inconclusive. The task of completely
      understanding this relationship has been encumbered not only by the complexity of
      neuronal responses, but also by nonlinear characteristics of the vascular
      response that are not correlated to neural activity. Repeated stimuli inducing
      replicable neural responses led to successively smaller BOLD amplitudes and
      delayed BOLD onset latencies when inter-stimulus intervals (ISIs) are shorter
      than 4-6 s, indicating significant nonlinearity between the BOLD signal and the
      underlying neuronal activity. We have provided evidence that large-vessel BOLD
      contributions could be the source of the nonlinearity (Zhang, N., Zhu, X.H.,
      Chen, W., 2008b. Investigating the source of BOLD nonlinearity in human visual
      cortex in response to paired visual stimuli. Neuroimage 43, 204-212). By
      utilizing the spin-echo (SE) BOLD fMRI method at high magnetic fields to suppress
      large-vessel BOLD contributions, we found that the BOLD signal from the micro
      vascular activity is replicable in response to replicated neuronal activities
      even at ISIs as short as approximately 1 s, suggesting that the micro-vascular
      BOLD activity is essentially a linear system. These results indicate that micro
      vascular BOLD signals should provide an accurate estimate of the amplitude of
      neuronal activity changes. Consequently, the findings are important in
      understanding and resolving the controversy in the neurovascular coupling
      relationship. In addition, the difference in BOLD response times between macro-
      and micro-vascular activities demonstrated herein will have a significant impact
      on functional connectivity and causality studies. Moreover, SE fMRI at high
      fields, due to its capability of accurately representing the strength of neural
      activity as well as its previously shown high spatial specificity to activated
      brain regions, is an ideal choice for mapping brain function and quantifying the
      stimulus-evoked brain activity noninvasively.

PMID- 19580877
TI  - Sex-dependent age modulation of frontostriatal and temporo-parietal activation
      during cognitive control.
AB  - Developmental functional imaging studies of cognitive control show progressive
      age-related increase in task-relevant fronto-striatal activation in male
      development from childhood to adulthood. Little is known, however, about how
      gender affects this functional development. In this study, we used event related
      functional magnetic resonance imaging to examine effects of sex, age, and their
      interaction on brain activation during attentional switching and interference
      inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear
      age correlations were observed across all subjects in task-specific frontal,
      striatal and temporo-parietal activation. Gender analysis revealed increased
      activation in females relative to males in fronto-striatal areas during the
      Switch task, and laterality effects in the Simon task, with females showing
      increased left inferior prefrontal and temporal activation, and males showing
      increased right inferior prefrontal and parietal activation. Increased prefrontal
      activation clusters in females and increased parietal activation clusters in
      males furthermore overlapped with clusters that were age-correlated across the
      whole group, potentially reflecting more mature prefrontal brain activation
      patterns for females, and more mature parietal activation patterns for males.
      Gender by age interactions further supported this dissociation, revealing
      exclusive female-specific age correlations in inferior and medial prefrontal
      brain regions during both tasks, and exclusive male-specific age correlations in
      superior parietal (Switch task) and temporal regions (Simon task). These findings
      show increased recruitment of age-correlated prefrontal activation in females,
      and of age-correlated parietal activation in males, during tasks of cognitive
      control. Gender differences in frontal and parietal recruitment may thus be
      related to gender differences in the neurofunctional maturation of these brain
      regions.

PMID- 19580876
TI  - Age-associated alterations in cortical gray and white matter signal intensity and
      gray to white matter contrast.
AB  - Prior studies have focused on patterns of brain atrophy with aging and age
      associated cognitive decline. It is possible that changes in neural tissue
      properties could provide an important marker of more subtle changes compared to
      gross morphometry. However, little is known about how MRI tissue parameters are
      altered in aging. We created cortical surface models of 148 individuals and
      mapped regional gray and white matter T1-weighted signal intensities from 3D
      MPRAGE images to examine patterns of age-associated signal alterations. Gray
      matter intensity was decreased with aging with strongest effects in medial
      frontal, anterior cingulate, and inferior temporal regions. White matter signal
      intensity decreased with aging in superior and medial frontal, cingulum, and
      medial and lateral temporal regions. The gray/white ratio (GWR) was altered
      throughout a large portion of the cortical mantle, with strong changes in
      superior and inferior frontal, lateral parietal, and superior temporal and
      precuneus regions demonstrating decreased overall contrast. Statistical effects
      of contrast changes were stronger than those of cortical thinning. These results
      demonstrate that there are strong regional changes in neural tissue properties
      with aging and tissue intensity measures may serve as an important biomarker of
      degeneration.

PMID- 19580878
TI  - Out-of-Africa again: a phylogenetic hypothesis of the genus Charaxes
      (Lepidoptera: Nymphalidae) based on five gene regions.
AB  - Despite the long popularity of Charaxes among collectors and researchers, their
      evolutionary history is largely unknown. The current and accepted species
      groupings and relationships within the genus are based exclusively on adult
      morphology and life histories. Here, we examine the monophyly and evolutionary
      affinities of the species-groups within the genus Charaxes and explore how they
      relate to members of their closest genera (Euxanthe, Polyura and Palla) using
      4167bp of sequence data from five (1 mitochondrial and 4 nuclear) gene regions.
      Within the proposed phylogenetic framework, we estimate ages of divergence within
      the genus and also reconstruct their historical biogeography. We included
      representatives of all known species-groups in Africa and Asia, all known species
      of Euxanthe and Palla and two exemplar species of Polyura. We found the genus
      Charaxes to be a paraphyletic group with regard to the genera Polyura and
      Euxanthe, contrary to the earlier assumption of monophyly. We found that 13 out
      of 16 morphologically defined species-groups with more than one species were
      strongly supported monophyletic clades. Charaxes nichetes is the sister group to
      all the other Charaxes. Polyura grouped with the Zoolina and Pleione species
      groups as a well-supported clade, and Euxanthe grouped with the Lycurgus species
      group. Our results indicated that the common ancestor of Charaxes diverged from
      the common ancestor of Palla in the mid Eocene (45 million years ago) in
      (Central) Africa and began diversifying to its extant members 15 million years
      later. Most of the major diversifications within the genus occurred between the
      late Oligocene and Miocene when the global climates were putatively undergoing
      drastic fluctuations. A considerable number of extant species diverged from
      sister species during the Pliocene. A dispersal-vicariance analysis suggests that
      many dispersal rather than vicariance events resulted in the distribution of the
      extant species. The genus Polyura and the Indo-Australian Charaxes are most
      likely the results of three independent colonizations of Asia by African Charaxes
      in the Miocene. We synonymize the genera Polyura (syn. nov.) and Euxanthe (syn.
      nov.) with Charaxes, with the currently circumscribed Charaxes subdivided into
      five subgenera to reflect its phylogeny.

PMID- 19580879
TI  - Molecular evidence for hybridization between two Australian desert skinks,
      Ctenotus leonhardii and Ctenotus quattuordecimlineatus (Scincidae: Squamata).
AB  - Australian scincid lizards in the genus Ctenotus constitute the most diverse
      vertebrate radiation in Australia. However, the evolutionary processes that have
      generated this diversity remain elusive, in part because both interspecific
      phylogenetic relationships and phylogeographic structure within Ctenotus species
      remain poorly known. Here we use nucleotide sequences from a mitochondrial locus
      and two nuclear introns to investigate broad-scale phylogeographic patterns
      within Ctenotus leonhardii and C. quattuordecimlineatus, two geographically
      widespread species of skinks that were found to have a surprisingly close genetic
      relationship in a previous molecular phylogenetic study. We demonstrate that the
      apparent close relationship between these ecologically and phenotypically
      distinct taxa is attributable to mitochondrial introgression from C.
      quattuordecimlineatus to C. leonhardii. In the western deserts, Ctenotus
      leonhardii individuals carry mtDNA lineages that are derived from C.
      quattuordecimlineatus mtDNA lineages from that geographic region. Coalescent
      simulations indicate that this pattern is unlikely to have resulted from
      incomplete lineage sorting, implicating introgressive hybridization as the cause
      of this regional gene-tree discordance.

PMID- 19580880
TI  - Generic relationships and dating of lineages in Winteraceae based on nuclear
      (ITS) and plastid (rpS16 and psbA-trnH) sequence data.
AB  - Phylogenetic analyses of representative species from the five genera of
      Winteraceae (Drimys, Pseudowintera, Takhtajania, Tasmannia, and Zygogynum s.l.)
      were performed using ITS nuclear sequences and a combined data-set of ITS+psbA
      trnH+rpS16 sequences (sampling of 30 and 15 species, respectively). Indel
      informativity using simple gap coding or gaps as a fifth character was examined
      in both data-sets. Parsimony and Bayesian analyses support the monophyly of
      Drimys, Tasmannia, and Zygogynum s.l., but do not support the monophyly of
      Belliolum, Zygogynum s.s., and Bubbia. Within Drimys, the combined data-set
      recovers two subclades. Divergence time estimates suggest that the splitting
      between Drimys and its sister clade (Pseudowintera+Zygogynum s.l.) occurred
      around the end of the Cretaceous; in contrast, the divergence between the two
      subclades within Drimys is more recent (15.5-18.5MY) and coincides in time with
      the Andean uplift. Estimates suggest that the earliest divergences within
      Winteraceae could have predated the first events of Gondwana fragmentation.

PMID- 19580881
TI  - Paraphyly of Cinclodes fuscus (Aves: Passeriformes: Furnariidae): implications
      for taxonomy and biogeography.
AB  - The Andes are a hotspot of global avian diversity, but studies on the historical
      diversification of Andean birds remain relatively scarce. Evolutionary studies on
      avian lineages with Andean-Patagonian distributions have focused on
      reconstructing species-level phylogenies, whereas no detailed phylogeographic
      studies on widespread species have been conducted. Here, we describe
      phylogeographic patterns in the Bar-winged Cinclodes (Cinclodes fuscus), a
      widespread and common species of ovenbird (Furnariidae) that breeds from Tierra
      del Fuego to the northern Andes. Traditionally, C. fuscus has been considered a
      single species composed of nine subspecies, but its long and narrow range
      suggests the possibility of considerable genetic variation among populations.
      Sequences of two mitochondrial genes revealed three discrete and geographically
      coherent groups of C. fuscus, occupying the southern, central, and northern
      Andes. Surprisingly, phylogenetic analyses indicated that these groups were more
      closely related to other species of Cinclodes than to each other. Relationships
      of the southern and northern C. fuscus clades to other species of Cinclodes were
      straightforward; in combination with available information on plumage,
      behavioral, and vocal variation, this suggests that each should be recognized as
      a distinct biological species. The central Andean group was paraphyletic with
      respect to C. oustaleti, and relationships among these taxa and C. olrogi were
      poorly resolved. We suggest that the central Andean C. fuscus should also be
      considered a different species, pending new information to clarify species limits
      in this group. These new phylogenetic data, along with recently developed
      methods, allowed us to review the biogeography of the genus, confirming southern
      South America and the central Andes as important areas for the diversification of
      these birds.

PMID- 19580882
TI  - Sudan azo dyes and Para Red degradation by prevalent bacteria of the human
      gastrointestinal tract.
AB  - Sudan azo dyes have genotoxic effects and ingestion of food products contaminated
      with Sudan I, II, III, IV, and Para Red could lead to exposure in the human
      gastrointestinal tract. In this study, we examined thirty-five prevalent species
      of human intestinal bacteria to evaluate their capacity to degrade Sudan dyes and
      Para Red. Among these tested bacterial strains, 23, 13, 33, 30, and 29 out of 35
      species tested were able to reduce Sudan I, II, III, IV, and Para Red,
      respectively, to some extent. Bifidobacterium infantis, Clostridium indolis,
      Enterococcus faecalis, Lactobacillus rhamnosus, and Ruminococcus obeum were able
      to reduce completely all four tested Sudan dyes and Para Red. Escherichia coli
      and Peptostreptococcus magnus were the only two strains that were not able to
      reduce any of the tested Sudan dyes and Para Red to any significant extent.
      Metabolites of the reduction of the tested Sudan dyes and Para Red by E. faecalis
      were isolated and identified by HPLC and LC/ESI-MS analyses and compared with
      authentic standards. Thus it appears that the ability to reduce Sudan dyes and
      Para Red except Sudan II is common among bacteria in the human colon.

PMID- 19580883
TI  - From pumps to prevention: recent advances in the treatment of type 1 diabetes.
AB  - Treatment options for pediatric patients living with type 1 diabetes mellitus
      (T1DM) have drastically changed over the past 30 years. Technological advances
      including the development of continuous subcutaneous insulin infusion (CSII) and
      continuous glucose monitoring (CGM) have allowed for improved insulin delivery
      and a better understanding of blood glucose fluctuations. Manipulations of CSII
      and CGM will allow for the development of an artificial pancreas; initial studies
      of this technology will be reviewed. New medications for the treatment of T1DM
      have been developed, such as rapid-acting insulins. Another area of exploration
      is the autoimmune process that causes beta-cell destruction. Immunomodulators
      used for T1DM prevention and secondary intervention will be reviewed.

PMID- 19580884
TI  - The impact of synthetic biology on drug discovery.
AB  - The emergence of synthetic biology is holding great hopes for providing solutions
      to the unmet needs of humankind. This review article describes how synthetic
      biology can deliver on this promise in the field of drug discovery by providing
      novel opportunities throughout the entire drug discovery process. Synthetic
      biology tools enable disease mechanisms and target identification to be
      elucidated and also provide avenues to discover small chemotherapeutic molecules
      or design novel biopharmaceuticals. Furthermore, synthetic biologists can design
      cost-effective microbial production processes for complex natural products, which
      could help overcome global drug shortages. These impressive advances have been
      achieved in only a few years, and are an indicator for the potential of synthetic
      biology.

PMID- 19580885
TI  - Occurrence of Trichodina heterodentata (Ciliophora: Trichodinidae) infesting
      tadpoles of Rhinella pombali (Anura: Bufonidae) in the Neotropical area.
AB  - Data on trichodinid ciliophorans in Brazil are scarce and generally do not use
      the modern silver-impregnation technique, which is essential to the taxonomy of
      the group. The present study reports not only on the first occurrence of
      Trichodina heterodentata in Brazil but also on the first record of this
      trichodinid infesting tadpoles of the species Rhinella pombali. This study also
      constitutes a second report on T. heterodentata from tadpoles. In September 2007,
      tadpoles were collected from a stream in a small farm in the agricultural area of
      the city of Juiz de Fora, southeastern Brazil. The ciliophorans found on the
      tadpoles' bodies and tails were submitted to techniques such as silver
      impregnation and scanning electron microscopy. Our biometric data of T.
      heterodentata population infesting Rhinella pombali were compared to five other
      South-African populations of T. heterodentata infesting tadpoles of Xenopus
      laevis laevis. Results were discussed in terms of low host specificity as well as
      the wide geographical distribution of this trichodinid.

PMID- 19580886
TI  - Sensitivity of dose-finding studies to observation errors.
AB  - The purpose of Phase I designs is to estimate the MTD (maximum tolerated dose, in
      practice a dose with some given acceptable rate of toxicity) while, at the same
      time, minimizing the number of patients treated at doses too far removed from the
      MTD. Our purpose here is to investigate the sensitivity of conclusions from dose
      finding designs to recording or observation errors. Certain toxicities may go
      undetected and, conversely, certain non-toxicities may be incorrectly recorded as
      dose-limiting toxicities. Recording inaccuracies would be expected to have an
      influence on final and within trial recommendations and, in this paper, we study
      in greater depth this question. We focus, in particular on three designs used
      currently; the standard '3+3' design, the grouped up-and-down design [M. Gezmu,
      N. Flournoy, Group up-and-down designs for dose finding. Journal of Statistical
      Planning and Inference 2006; 136 (6): 1749-1764.] and the continual reassessment
      method (CRM, [J. O'Quigley, M. Pepe, L. Fisher, Continual reassessment method: a
      practical design for phase 1 clinical trials in cancer. Biometrics 1990; 46 (1):
      33-48.]). A non-toxicity incorrectly recorded as a toxicity (error of first kind)
      has a greater influence in general than the converse (error of second kind).
      These results are illustrated via figures which suggest that the standard '3+3'
      design in particular is sensitive to errors of the second kind. Such errors can
      have a very important impact on drug development in that, if carried through to
      the Phase 2 and Phase 3 studies, we can significantly increase the probability of
      failure to detect efficacy as a result of having delivered an inadequate dose.

PMID- 19580887
TI  - Recruiting minorities where they receive care: Institutional barriers to cancer
      clinical trials recruitment in a safety-net hospital.
AB  - INTRODUCTION: Most research on the barriers to recruitment of ethnic and racial
      minorities focuses on patient factors. The purpose of this exploratory case study
      was to examine how institutional factors impacted recruitment and enrollment in a
      public hospital clinic frequented by minority patients. METHODS: We used
      ethnographic methods (observations of patient-provider interactions and semi
      structured interviews) to document and explain how a number of institutional
      barriers hindered trials enrollment in a public hospital outpatient breast cancer
      clinic. RESULTS: We identified two categories of institutional barriers: (1)
      organizational climate, and (2) research specific resources. Organizational
      climate included qualities of the clinic and hospital such as the clinic
      structure (clinic hours, patient assignment method), the interdisciplinary care
      team, the lack of continuity of care, and competing provider priorities of
      clinical care, teaching, and research. Research specific resources included:
      staff, funds and institutional status to facilitate opening a range of trials;
      and linguistically and literacy-appropriate research resources. CONCLUSION:
      Although we cannot determine from our qualitative data the relative impact of
      different kinds of barriers (e.g. patient, provider, institutional barriers), our
      data highlights the need to address the role of institutional barriers in efforts
      to improve minority recruitment to clinical trials. Recruiting participants in
      safety-net settings may be a reasonable strategy for increasing accrual of ethnic
      and racial minority patients to cancer clinical trials. However, our qualitative
      data suggest that while opening protocols for accrual at minority-serving
      institutions may signal nominal access to trials, achieving substantive access
      may require further steps to overcome substantial institutional barriers.

PMID- 19580888
TI  - Genetic determinants of virulence, antibiogram and altered biotype among the
      Vibrio cholerae O1 isolates from different cholera outbreaks in India.
AB  - Cholera diarrhea is still a major health challenge for a large part of globe.
      Global replacement of Vibrio cholerae classical biotype by El Tor biotype,
      emergence of O139 serogroup and rapid spread of antibiotic resistant strains
      indicate the continuous evolution in V. cholerae. In this study, 114 V. cholerae
      O1 serotype Ogawa isolates, collected from different cholera outbreaks in
      different regions of India between 2004 and 2007 were subjected to biochemical,
      immunological and molecular characterization. All the isolates were PCR positive
      for various toxigenic, pathogenic and regulatory genes, viz. ompW, ctxB, rfbO1,
      tcp, zot, rtxC, ace, hlyA, ompU and toxR. The antibiogram studies of isolates
      revealed the resistance towards several antibiotics including nalidixic acid, co
      trimoxazole, streptomycin, nitrofurantoin and polymyxin B. However, antibiogram
      of the strains confirmed susceptibility to tetracycline and chloramphenicol in
      all the isolates. This study also substantiated the wide spread of class 1
      integrons and SXT elements (mobile genetic elements for antibiotic resistance) in
      clinical isolates in India. Sequencing of cholera toxin (ctxB) gene revealed the
      replacement of traditional ctxB of El Tor biotype with ctxB of classical biotype
      in all the O1 El Tor strains collected since 2004. In addition, in 2007, a new
      variant of O1 El Tor strain with further modifications in ctxB of classical
      biotype is discovered among the Indian isolates.

PMID- 19580890
TI  - pI-based fractionation of serum proteomes versus anion exchange after enhancement
      of low-abundance proteins by means of peptide libraries.
AB  - The pre-treatment of biological extracts with the aim of detecting very low
      abundance proteins generates complexity requiring a proper fractionation.
      Therefore the success of identifying all newly detectable species depends on the
      selected fractionation methods. In this context and starting from a human serum,
      where the dynamic concentration range was reduced by means of a preliminary
      treatment with a combinatorial hexapeptide ligand library, we fractionated the
      sample using a novel method based on the differences in isoelectric points of
      proteins by means of Solid-State Buffers (SSB) associated with cation exchangers.
      The number of fractions was limited to four and was compared to a classical anion
      exchange method generating the same number of fractions. What was observed is
      that when using SSB technology the protein redundancy between fractions was
      significantly reduced compared to ion exchange fractionation allowing thus a
      better detection of novel species. The analysis of trypsinized protein fractions
      by nanoLC-MS/MS confirmed that the SSB technology used is more discriminant than
      anion exchange chromatography fractionation. A sample fractionation by SSB after
      the reduction of dynamic concentration range can be accomplished without either
      adjustment of pH and ionic strength or protein concentration and cleanup. Both
      advantages over either classical chromatography or isoelectric fractionations
      allow approaching the discovery of markers of interest under easier conditions
      applicable in a variety of fields of investigation.

PMID- 19580889
TI  - Application of proteomics to neutrophil biology.
AB  - Polymorphonuclear leukocytes or neutrophils are a primary effector cell of the
      innate immune system and contribute to the development of adaptive immunity.
      Neutrophils participate in both the initiation and resolution of inflammatory
      responses through a series of highly coordinated molecular and phenotypic
      changes. To accomplish these changes, neutrophils express numerous receptors and
      use multiple overlapping and redundant signal transduction pathways.
      Dysregulation of the activation or resolution pathways plays a role in a number
      of human diseases. A comprehensive understanding of the regulation of neutrophil
      responses can be provided by high throughput proteomic technologies and
      sophisticated computational analysis. The first steps in the application of
      proteomics to understanding neutrophil biology have been taken. Here we review
      the application of expression, structural, and functional proteomic studies to
      neutrophils. Although defining the complex molecular events associated with
      neutrophil activation is in the early stages, the data generated to date suggest
      that proteomic technologies will dramatically enhance our understanding of
      neutrophil biology.

PMID- 19580891
TI  - Effects of a synonymous variant in exon 9 of the CD44 gene on pre-mRNA splicing
      in a family with osteoporosis.
AB  - In a previous linkage study, suggestive linkage to osteoporosis was observed in
      marker D11S1392 on chromosome 11p12. The CD44 gene, found at this locus, was
      sequenced in one of the families studied. Sequencing all coding regions and
      promoter in affected and non-affected family members revealed a number of
      sequence variants, one of which was found to be linked and inherited identical by
      descent together with the linked STR allele. This G to A variant, which does not
      cause an amino acid change, was found in exon 9 of the CD44 gene, 32 base pairs
      upstream from the exon-intron junction. Preliminary analysis using a
      bioinformatics tool suggested that the presence of the A allele abolished an exon
      splicing enhancer (ESE) site, thus possibly affecting RNA splicing. It was
      observed using an exon-trapping vector, that in the presence of the A allele,
      only one transcript was observed in RAW264.7 cells, as opposed to two transcripts
      transcribed in the presence of the G allele. These observations suggest that the
      linked synonymous variant found in exon 9 of the CD44 gene might be increasing
      susceptibility to osteoporosis in this family by affecting the splicing
      mechanism.

PMID- 19580894
TI  - Co-author or teacher?

PMID- 19580892
TI  - Development of a novel DNA SynCon tetravalent dengue vaccine that elicits immune
      responses against four serotypes.
AB  - The increased transmission and geographic spread of dengue fever (DF) and its
      most severe presentations, dengue hemorrhagic fever (DHF) and dengue shock
      syndrome (DSS), make it one of the most important mosquito-borne viral disease of
      humans. Four distinct serotypes of dengue viruses are transmitted to humans
      through the bites of the mosquitoes. Currently there is no vaccine or antiviral
      drug against DV infections. Cross-protection between dengue virus serotypes is
      limited and antibody dependent enhancement (ADE) contributes significantly to the
      severity of the disease. The major challenge is to induce a broad durable immune
      response against all four serotypes of dengue virus simultaneously while avoiding
      the possible exacerbation of risk of developing the severe forms of disease
      through incomplete or modified responses. In order to address this worldwide
      concern, we present a synthetic consensus (SynCon) human codon optimized DNA
      vaccine that elicits immunity against all four dengue serotypes. We cloned
      consensus DIII domain of E protein from all serotypes and expressed them as a
      single open reading frame in a mammalian expression vector, called pDV-U-DIII
      (dengue-vaccine universal). In mice, this dengue-universal construct elicits
      significant level of anti-DIII antibody that neutralizes all four dengue subtypes
      and prevents cell death induced by dengue infection. This is the first SynCon DNA
      vaccine that provides tetravalent immunity against all four serotypes of dengue
      virus.

PMID- 19580895
TI  - Starting a health care system green team.
AB  - The health care industry is often overlooked as a major source of industrial
      pollution, but as this becomes more recognized, many health care facilities are
      beginning to pursue green efforts. The OR is a prime example of an area of health
      care that is working to lessen its environmental impact. Nurses can play key
      roles in identifying areas of waste and presenting ideas about recovering
      secondary materials. For instance, although infection prevention measures
      encourage one-time use of some products, nurses can investigate how to reprocess
      these items so they can be reused. This article examines how the efforts of a
      Green Team can affect a hospital's waste stream. A health care Green Team can
      facilitate a medical facility's quest for knowledge and awareness of its effect
      on the waste stream and environment.

PMID- 19580896
TI  - Postoperative telephone calls: timing is everything.
AB  - Having nurses contact same-day surgical patients by telephone early in the
      patients' recovery process may help guide recovery, but there are no guidelines
      as to the best time to make these calls. A convenience sample of 77 patients
      undergoing same-day knee arthroscopy surgery at a large health care center in the
      northeastern United States was recruited to examine the best time for telephone
      follow-up by a nurse. Overall patient experiences and teaching-learning needs
      also were investigated through open-ended questions. Findings suggest that
      continuous contact by nurses in the recovery period helped patients discuss and
      process the surgical experience. Telephone calls may be the most helpful to
      patients between 12 and 24 hours after surgery.

PMID- 19580897
TI  - Adopting preoperative fasting guidelines.
AB  - In 1999, the American Society of Anesthesiologists adopted preoperative fasting
      guidelines to enhance the quality and efficiency of patient care. Guidelines
      suggest that healthy, non-pregnant patients should fast six hours from solids and
      two hours from liquids. Although these guidelines are in place, studies suggest
      that providers are still using the blanket statement "NPO after midnight" without
      regard to patient characteristics, the procedure, or the time of the procedure.
      Using theory to help change provider's beliefs may help make change more
      successful. Rogers' Theory of Diffusion of Innovations can assist in changing
      long-time practice by laying the groundwork for an analysis of the benefits and
      disadvantages of proposed changes, such as changes to fasting orders, while
      helping initiate local protocols instead of additional national guidelines.

PMID- 19580898
TI  - Telesurgery: providing remote surgical observations for students.
AB  - Meeting students' needs for a valuable experience in the OR presents many
      challenges especially in a non-teaching hospital setting. Creating a means for
      students to observe surgery from a remote site can meet students' needs without
      causing scheduling, supervision, or patient care problems for the OR staff
      members who are hosting the students. Incorporating existing technology and
      recruiting staff members and physicians who are willing to participate and share
      their knowledge with students helps to create a valuable experience for all
      participants.

PMID- 19580899
TI  - Streamlining the OR.
AB  - Streamlining the OR can increase physician and staff member satisfaction and
      improve efficiencies. Leaders at the West Florida Division for Healthcare
      Corporation of America took on the task of streamlining technology and processes
      for 16 facilities with the goal of surgical volume growth. After assessing the
      current processes, the team developed a plan to streamline the OR in four major
      areas. For each area, they paired technology with a process to accomplish the
      goal. The plan included improving the virtual supply inventory set up and case
      picking process, coupling the procedure groups and procedure set up with the
      scheduling process, improving the preference card set up and maintenance system,
      and pairing documentation with the pre-admission and chart completion process.

PMID- 19580900
TI  - A people to people nursing experience in Russia.

PMID- 19580905
TI  - National patient safety goals and implementation.

PMID- 19580913
TI  - Is the mirror neuron system involved in imitation? A short review and meta
      analysis.
AB  - It has been suggested that the mirror neuron system provides an important neural
      substrate for humans' ability to imitate. Mirror neurons have been found during
      single-cell recordings in monkeys in area F5 and PF. It is believed that the
      human equivalent of this mirror system in humans is the pars opercularis of the
      inferior frontal gyrus (area 44) and the rostral part of the inferior parietal
      lobule. This article critically reviews published fMRI studies that examined the
      role of frontal and parietal brain regions in imitation. A meta-analysis using
      activation likelihood estimation (ALE) revealed that the superior parietal
      lobule, inferior parietal lobule, and the dorsal premotor cortex but not the
      inferior frontal gyrus, are all commonly involved in imitation. An additional
      meta-analysis using a label-based review confirmed that in the frontal lobe, the
      premotor cortex rather than the inferior frontal gyrus is consistently active in
      studies investigating imitation. In the parietal region the superior and inferior
      parietal lobules are equally activated during imitation. Our results suggest that
      parietal and frontal regions which extend beyond the classical mirror neuron
      network are crucial for imitation.

PMID- 19580916
TI  - Neuromodulating mice and men: Are there functional species differences in
      neurotransmitter concentration?
AB  - I examine evidence that the concentration of certain modulatory neurotransmitters
      varies across species, including differences between rodents and primates.
      Microdialysis studies indicate that the baseline concentration of serotonin,
      norepinephrine, dopamine, and acetylcholine, as measured in the prefrontal cortex
      of awake animals, may differ between rats and macaque monkeys. These differences
      may extend to mice and humans, as well. If there are differences in the tonic
      concentration of these neurotransmitters, this may affect the functioning of
      these transmitter systems in multiple ways, including potential effects on
      neuropsychiatric conditions such as the various mental illnesses and modeling of
      them in animals. Species differences in transmitter concentration may also have
      neuropharmacological implications, and may be relevant to the phenomenon of
      differences in speed of drug response between humans and rodents. This paper is
      divided into three sections that address related questions about the potential
      concentration differences: (1) Are there species differences in baseline
      neurotransmitter concentration? (2) Are the putative differences functional? (3)
      What might the functional differences be? Consideration of the existing evidence
      indicates that there may indeed be functional species differences in the
      modulatory transmitter systems.

PMID- 19580915
TI  - Intelligence and neural efficiency.
AB  - We review research on the neural efficiency hypothesis of intelligence, stating
      that brighter individuals display lower (more efficient) brain activation while
      performing cognitive tasks [Haier, R.J., Siegel, B.V., Nuechterlein, K.H.,
      Hazlett, E., Wu, J.C., Paek, J., Browning, H.L., Buchsbaum, M.S., 1988. Cortical
      glucose metabolic rate correlates of abstract reasoning and attention studied
      with positron emission tomography. Intelligence 12, 199-217]. While most early
      studies confirmed this hypothesis later research has revealed contradictory
      evidence or has identified some moderating variables like sex, task type, task
      complexity or brain area. Neuroscientific training studies suggest that neural
      efficiency also seems to be a function of the amount and quality of learning.
      From integrating this evidence we conclude that neural efficiency might arise
      when individuals are confronted with tasks of (subjectively) low to moderate task
      difficulty and it is mainly observable for frontal brain areas. This is true for
      easier novel cognitive tasks or after sufficient practice allowing participants
      to develop appropriate (efficient) strategies to deal with the task. In very
      complex tasks more able individuals seem to invest more cortical resources
      resulting in positive correlations between brain usage and cognitive ability.
      Based on the reviewed evidence we propose future empirical approaches in this
      field.

PMID- 19580917
TI  - Contact dermatitis. Preface.

PMID- 19580918
TI  - Recognizing and testing allergens.
AB  - The diagnosis of a contact allergy requires several important and essential
      steps, because the failure to recognize a contact allergy can occur in any of the
      various stages of the contact allergy investigation. If the results of the skin
      tests are negative for a patient for whom a diagnosis of allergic contact
      dermatitis has been proposed, one has to go back to the beginning, that is, with
      a thoroughgoing anamnesis of the patient (perhaps with a visit to his or her
      environment). The assumed allergens must be retested (perhaps in another
      concentration, with another vehicle, or with another testing method), and
      additional allergens must be tested. The patient can also be asked to keep a
      journal, in the hope that a correlation can be discerned between exposure to a
      substance and the occurrence of the skin problems. Once an allergen has been
      identified, it is the dermatologist's task to provide specific advice about the
      products that have to be avoided, or about the products that can safely be used,
      because subjects sensitive to specific ingredients must avoid products containing
      them.

PMID- 19580919
TI  - Hand/face/neck localized pattern: sticky problems--resins.
AB  - Plastic resin systems have an increasingly diverse array of applications but also
      induce health hazards, the most common of which are allergic and irritant contact
      dermatitis. Contact urticaria, pigmentary changes, and photoallergic contact
      dermatitis may occasionally occur. Other health effects, especially respiratory
      and neurologic signs and symptoms, have also been reported. These resin systems
      include epoxies, the most frequent synthetic resin systems to cause contact
      dermatitis, (meth)acrylics, polyurethanes, phenol-formaldehydes, polyesters,
      amino resins (melamine-formaldehydes, urea-formaldehydes), polyvinyls,
      polystyrenes, polyolefins, polyamides and polycarbonates. Contact dermatitis
      usually occurs as a result of exposure to the monomers and additives in the
      occupational setting, although reports from consumers, using the raw materials or
      end products periodically surface. Resin- and additive-induced direct contact
      dermatitis usually presents on the hands, fingers, and forearms, while facial,
      eyelid, and neck involvement may occur through indirect contact, eg, via the
      hands, or from airborne exposure. Patch testing with commercially available
      materials, and in some cases the patient's own resins, is important for
      diagnosis. Industrial hygiene prevention techniques are essential to reduce
      contact dermatitis when handling these resin systems.

PMID- 19580920
TI  - Hand dermatitis: a focus on allergic contact dermatitis to biocides.
AB  - Hand dermatitis is a common disease of the skin resulting in significantly
      decreased quality of life. Allergic contact dermatitis is a frequent cause of
      hand dermatitis. Recent studies have revealed that biocides used as preservatives
      are frequent allergens affecting the hands. This article reviews common biocides
      implicated in hand dermatitis.

PMID- 19580921
TI  - Patterns of cosmetic contact allergy.
AB  - Certain patterns of dermatitis, such as those affecting the face, eyelids, lips,
      and neck, should raise the suspicion of a cosmetic-related contact allergy. Patch
      testing with a broad screening series, supplemented by a patient's own personal
      care products, should be considered when evaluating patients with suspected
      cosmetic dermatitis. Once the offending allergen is identified, an avoidance
      regimen should be established to avoid further exposure.

PMID- 19580922
TI  - Clinical patterns of hand and foot dermatitis: emphasis on rubber and chromate
      allergens.
AB  - The anatomic distribution of dermatitis affecting the hands and feet can provide
      clues to the likelihood that a contact allergen is provoking the dermatitis.
      Dermatitis presenting on the hands or feet, but not both, is more likely because
      of allergic contact dermatitis, whereas dermatitis affecting both the hands and
      feet is more likely a result of a systemic cause. Exceptions are reviewed in this
      article. When allergic contact dermatitis affects only the hands and feet, rubber
      chemicals and chromates are the most common allergens. Pattern recognition can
      assist with choice of patch test allergens, counseling regarding routes of
      exposure, and selection of alternative contactants.

PMID- 19580923
TI  - Unusual patterns in contact dermatitis: medicaments.
AB  - Allergic contact dermatitis to topical medicaments occurs often. Common
      medicaments associated with allergic contact dermatitis include topically applied
      antibiotics, antihistamines, nonsteroidal antiinflammatory drugs, anesthetics,
      and corticosteroids. In cases of suspected allergic contact dermatitis,
      medicaments that the patient is using should be included when patch testing. Body
      sites susceptible to allergic contact dermatitis to topical medicaments include
      scalp, face, anogenital area, and lower extremities.

PMID- 19580925
TI  - Factors associated with textile pattern dermatitis caused by contact allergy to
      dyes, finishes, foams, and preservatives.
AB  - From as early as 1869, textile dyes and subsequently finishes have been reported
      to cause various manifestations of contact dermatitis, from mild to severe and
      debilitating. The European Union, through Directive (2002/61/EC) to restrict the
      marketing and use of certain dangerous substances and preparations (azo
      colorants) in textile and leather products, has taken the worldwide lead in
      restricting some dyes as a result of their carcinogenic nature. Given the recent
      discovery of the new route to contact dermatitis, it is important to continue to
      be vigilant for new and unexpected sources of allergens from textile, apparel,
      and furniture items.

PMID- 19580924
TI  - Clinical patterns of phytodermatitis.
AB  - Exposure to plants is very common, through leisure or professional activity. In
      addition, plant products and botanic extracts are increasingly present in the
      environment. Cutaneous adverse reactions to plants and their derivatives occur
      fairly frequently, and establishing the correct diagnosis is not always easy. The
      astute clinician relies on a detailed history and a careful skin examination to
      substantiate his opinion. This article reviews the characteristic clinical
      patterns of phyto- and phytophotodermatitis and some less common presentations.

PMID- 19580926
TI  - Patient education to enhance contact dermatitis evaluation and testing.
AB  - Patient education plays an important role in empowering patients who have
      allergic contact dermatitis. Having the knowledge about a disease process does
      not guarantee healthy behaviors. Through careful assessment of educational needs,
      awareness of stages of change that adults go through, and use of resources
      available to members of the American Contact Dermatology Society, nurses can
      provide patient education that completes the patch testing process.

PMID- 19580914
TI  - Persistent cognitive dysfunction after traumatic brain injury: A dopamine
      hypothesis.
AB  - Traumatic brain injury (TBI) represents a significant cause of death and
      disability in industrialized countries. Of particular importance to patients the
      chronic effect that TBI has on cognitive function. Therapeutic strategies have
      been difficult to evaluate because of the complexity of injuries and variety of
      patient presentations within a TBI population. However, pharmacotherapies
      targeting dopamine (DA) have consistently shown benefits in attention, behavioral
      outcome, executive function, and memory. Still it remains unclear what aspect of
      TBI pathology is targeted by DA therapies and what time-course of treatment is
      most beneficial for patient outcomes. Fortunately, ongoing research in animal
      models has begun to elucidate the pathophysiology of DA alterations after TBI.
      The purpose of this review is to discuss clinical and experimental research
      examining DAergic therapies after TBI, which will in turn elucidate the
      importance of DA for cognitive function/dysfunction after TBI as well as
      highlight the areas that require further study.

PMID- 19580927
TI  - Relevance and avoidance of skin-care product allergens: pearls and pitfalls.
AB  - Patch testing can be particularly rewarding when skin-care product allergens are
      identified. Careful determination of relevance, followed by careful education
      regarding allergen avoidance, can result in dramatic clinical improvement.
      Several common clinical scenarios are reviewed with a focus on pragmatic
      solutions to heighten positive patient outcomes.

PMID- 19580928
TI  - Acute and recurrent vesicular hand dermatitis.
AB  - The terminology of eruptive, symmetric, vesicular, and/or bullous dermatitis on
      the palms and/or palmar aspects or sides of the fingers includes the terms
      pompholyx, dyshidrosis, and dyshidrotic eczema. This article presents the case
      for a standard, broad definition of this condition and reviews the epidemiology,
      clinical features, etiology, and treatment of acute and recurrent vesicular hand
      dermatitis with special emphasis on endogenous causes.

PMID- 19580929
TI  - Systemic contact dermatitis.
AB  - Systemic contact dermatitis (SCD) describes a cutaneous eruption in response to
      systemic exposure to an allergen. The exact pathologic mechanism remains
      uncertain. The broad spectrum of presentations that are often nonspecific can
      make it difficult for the clinician to suspect this disease, but it is an
      important diagnosis to consider in cases of recalcitrant, widespread, or
      recurrent dermatitis, in which patch testing often reveals allergy to nickel or
      balsam of Peru. Diagnosis and appropriate management can be life-altering for
      affected patients. This article on SCD provides an overview of the disease with
      descriptions of common allergens and some insight into the possible mechanism of
      action seen in SCD.

PMID- 19580930
TI  - Management of occupational dermatitis.
AB  - Contact dermatitis is the most common occupational skin disorder, responsible for
      up to 30% of all cases of occupational disease in industrialized nations.
      Epidemiologic data suggest that contact dermatitis accounts for 90% to 95% of all
      cases of occupational skin disease, imposing considerable social and economic
      implications. Occupational contact dermatitis is broadly classified into allergic
      and irritant subtypes. Irritant contact dermatitis is widely quoted in the
      literature to account for 80% of occupational contact dermatitis cases, with
      allergic cases held responsible for the remaining 20%.

PMID- 19580931
TI  - Impact of regulation on contact dermatitis.
AB  - Contact dermatitis is a serious public health and dermatologic concern. The
      prevalence of contact dermatitis in the United States was estimated to be 13.6
      per 1000 population according to the National Health and Nutritional Examination
      Survey using physical examinations by dermatologists of a selected sample of
      Americans. The American Medical Care Survey estimated that for all American
      physicians dermatitis is the second most common dermatologic diagnosis proffered.
      It is essential that government, industry, and dermatologists work together to
      enhance regulatory methods to control and prevent contact allergy epidemics.
      Increased knowledge and awareness of occupational skin diseases by dermatologists
      and other health care professionals will assist in achieving national public
      health goals. This article reviews governmental regulations-some helpful for
      patients and workers and some not helpful for dermatologists in their quest to
      assist patients with contact dermatitis.

PMID- 19580932
TI  - Preface. New perspectives in equine colic.

PMID- 19580933
TI  - Clinical governance, clinical audit, and the potential value of a database of
      equine colic surgery.
AB  - "Clinical governance" is the term used to describe a systematic approach to
      maintaining and improving the quality of patient care within a health system.
      This article introduces the concept of clinical governance as a tool for
      improving the quality of care. It also discusses the potential value of a large
      database of colic surgery in implementing some of the components of clinical
      governance in the field of equine colic surgery.

PMID- 19580935
TI  - Prognosticating equine colic.
AB  - Prognosticating survival in horses with colic is challenging because of the
      number of diseases and pathophysiologic processes that can cause the behavior.
      Although the treatment of horses with colic has improved dramatically over the
      years, case fatality can still be high because of the delay in recognizing the
      problem, the time delay inherent in receiving veterinary care, and the lack of
      effective treatment for the more severe diseases. Intensive case management and
      surgery for these horses may be expensive and emotionally draining for owners;
      therefore, providing an accurate prognosis is key to decisions needed for case
      management. This article is dedicated to recent advances in applying a prognosis
      for survival in horses at higher risk for a fatal outcome.

PMID- 19580934
TI  - The bacterial community of the horse gastrointestinal tract and its relation to
      fermentative acidosis, laminitis, colic, and stomach ulcers.
AB  - The gastrointestinal tract of the horse has unique characteristics that make it
      well suited for the ingestion and utilization of roughage. The horse is
      considered a simple-stomached herbivore and is classed as a hindgut fermenter.
      The upper segments of the gastrointestinal tract resemble those of a typical
      simple-stomached animal. The lower have undergone modification to become
      voluminous and host to a large number of microbial populations similar to those
      of the compartmental stomach of ruminant animals. The main advantage of this
      arrangement is the ability of the horse to extract valuable nutrients from the
      diet before digesta reaches the hindgut where the rigid structural components
      that resisted enzymatic digestion at the small intestinal level undergo extensive
      fermentation processes.

PMID- 19580936
TI  - Parasitism and colic.
AB  - Equids are hosts to dozens of species of internal parasites that infect no other
      domestic animals. Virtually all horses, especially those exposed to pasture,
      experience some level of parasitism continuously. Despite pathologic evidence of
      parasitic damage in various organs and tissues, few parasitisms are manifested
      systemically in well-managed horses. Contrary to conventional wisdom, only three
      common parasitisms of horses are likely to be manifested as colic: Strongylus
      vulgaris, Parascaris equorum, and Anoplocephala perfoliata. This article
      discusses the life cycles, pathophysiology, manifestations and clinical findings,
      treatment, and management of these three common parasitisms. It also discusses
      related aspects of several other parasitisms that are unlikely to cause colic.

PMID- 19580937
TI  - Coagulopathies in horses with colic.
AB  - The most common coagulopathy in horses with colic is a hypercoagulable state
      associated with disseminated intravascular coagulation. The intensity of this
      coagulopathy depends on the severity and duration of the gastrointestinal lesion,
      with the ischemic and inflammatory problems and peritonitis being the most
      frequently affected by coagulopathies. Early initiation of prophylactic therapy
      significantly reduces the severe hypercoagulable state in horses with intestinal
      conditions which are recognized to be at high risk for disseminated intravascular
      coagulation. In addition to the systemic coagulopathy observed in horses with
      colic, a peritoneal coagulopathy independent from that occurring in blood has
      been observed, and its recognition and assessment may have clinical usefulness in
      the diagnosis of the gastrointestinal diseases and outcome.

PMID- 19580938
TI  - Update on treatments for endotoxemia.
AB  - Endotoxemia is a major cause of morbidity and mortality in horses affected by
      colic. This article briefly reviews the pathogenesis of endotoxemia in horses
      with colic, reviews current established treatments, and describes new advances in
      the treatment of endotoxemia.

PMID- 19580939
TI  - Update on recent advances in equine abdominal surgery.
AB  - In recent years important advancements in colic surgery have led to improved
      prediction of survival rates, better survival rates, and decreased complication
      rates. This article describes several modalities to combat and prevent incisional
      hernia and intestinal adhesion formation in horses undergoing colic surgery.
      These modalities have had a positive impact on reducing complications in horses
      after surgery.

PMID- 19580940
TI  - New perspectives in equine gastric ulcer syndrome.
AB  - Equine gastric ulcer syndrome (EGUS) is common in horses. A history of mild
      intermitted recurrent colic signs after eating is noted in many horses.
      Management of horses with abdominal pain caused by gastric ulcers is especially
      difficult, because non-steroidal anti-inflammatory agents, typically used to
      control abdominal pain, may exacerbate this condition. Effective pharmacologic
      agents are available to treat EGUS and eliminate abdominal pain, but more
      comprehensive measures of environmental and dietary management are needed to
      manage horses with EGUS and prevent recurrence. This article focuses on the
      history, clinical signs, diagnosis, and management of horses with abdominal pain
      associated with gastric ulcers. The primary goal is to provide an understanding
      of EGUS and to review effective pain management and specific antiulcer treatments
      and management strategies in horses with EGUS.

PMID- 19580941
TI  - Inflammatory bowel disease in horses.
AB  - This article discusses types of inflammatory bowel disease in horses, including
      pathologic findings and proposed causes. The diagnosis of inflammatory bowel
      disease is presented in detail, including minimum database, rectal palpation,
      abdominal ultrasound, abdominocentesis, biopsy procedures, and absorption tests.
      Treatment recommendations and prognosis are also discussed.

PMID- 19580942
TI  - Impactions of the small and large intestines.
AB  - Impactions of the small and large intestines are frequently diagnosed as the
      cause of colic in horses. An impaction is an accumulation of dehydrated ingesta
      in a portion of the digestive tract, typically at sites where the intestinal
      diameter decreases. The specific pathogenesis for impactions is not fully
      understood, although risk factors have been identified for several types of
      impactions. Treatment for impactions includes withholding feed until the
      impaction passes, rehydrating the ingesta, and, if necessary, administering
      analgesic agents. In severe cases, surgery may be necessary to relieve the
      impaction. This article discusses clinical signs, diagnosis, treatment (both drug
      and surgical options), and prognosis for impactions of the duodenum, jejunum,
      ileum, cecum, and small and large colons in horses.

PMID- 19580943
TI  - Enteroliths and other foreign bodies.
AB  - This article focuses on obstructive diseases of the large intestine (large and
      small colons) caused by intraluminal bodies. Large intestinal obstructions from
      intraluminal bodies can be divided into the following categories: enteroliths or
      mineral concretions, bezoars (hair or plant material), and ingested foreign
      objects. Clinical presentation and treatment of obstructive diseases are
      presented in this article and are similar regardless of the cause.

PMID- 19580944
TI  - New perspectives in postoperative complications after abdominal surgery.

PMID- 19580945
TI  - Postoperative ileus: pathogenesis and treatment.
AB  - Surgical manipulation of the intestines activates intestinal macrophages that
      release cytokines and nitric oxide, which results in inhibition of intestinal
      motility. Subsequent infiltration of circulating leukocytes into the intestinal
      wall contributes to cytokine and nitric oxide release and exacerbates ileus.
      Other factors contributing to ileus are endotoxemia; edema of the intestine wall
      subsequent to excessive fluid therapy; hypocalcemia; and long abdominal
      incisions. Because treatment of ileus with prokinetic drugs has not proven to be
      very effective, efforts should be directed at reducing its severity. Strategies
      which reduce the severity of ileus include pretreatment with a nonsteroidal anti
      inflammatory drug, minimizing the length of the abdominal incision, reducing
      intestinal manipulation, intraoperative lidocaine infusion, correction of
      hypocalcemia, limiting the volume of intravenous fluids to prevent intestinal
      edema, and administration of alpha(2) antagonists.

PMID- 19580946
TI  - Acute diarrhea in hospitalized horses.
AB  - The development of diarrhea among hospitalized horses is a major concern for
      equine veterinary hospitals and referral centers. It is a potential complication
      of hospitalization for surgical or medical procedures and can contribute to the
      morbidity and mortality of horses with gastrointestinal and non-gastrointestinal
      diseases. Unfortunately, it can be difficult to pinpoint the exact cause of acute
      diarrhea or colitis, and in most cases, the specific etiologic agent is
      presumptive or undetermined. This article discusses the major etiologic agents of
      diarrhea in hospitalized horses, considers factors that place hospitalized horses
      at special risk for diarrhea, and examines several infectious colitis outbreaks
      that have occurred at veterinary referral centers.

PMID- 19580947
TI  - Equine grass sickness: epidemiology, diagnosis, and global distribution.
AB  - Equine grass sickness (EGS) is recognized as a debilitating and predominantly
      fatal neurodegenerative disease affecting grazing equids. The gastrointestinal
      tract is the most severely affected body system, resulting in the main clinical
      signs of colic (acute grass sickness), weight loss, or dysphagia (chronic grass
      sickness). EGS predominantly occurs within Great Britain, although it is also
      recognized in regions of mainland Europe, and mainly affects young horses with
      access to pasture in the springtime. There is strong evidence of an association
      between EGS and the type C toxins produced by the bacterium Clostridium
      botulinum. This article covers the clinical aspects, epidemiology, and global
      distribution of EGS, along with comparisons with botulism and developments in
      disease prevention.

PMID- 19580948
TI  - Demystifying incretin therapy for type 2 diabetes. Introduction.

PMID- 19580949
TI  - Unraveling the science of incretin biology.
AB  - Type 2 diabetes mellitus has become an enormous and worldwide healthcare problem
      that is almost certain to worsen. Current therapies, which address glycemia and
      insulin resistance, have not adequately addressed the complications and treatment
      failures associated with this disease. New treatments based on the incretin
      hormones provide a novel approach to address some components of the complex
      pathophysiology of type 2 diabetes. The purpose of this review is to elucidate
      the science of the incretin hormones and describe the incretin effect and its
      regulatory role in beta-cell function, insulin secretion, and glucose metabolism.
      The key endogenous hormones of incretin system are glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); a key
      enzymatic regulator of these hormones is dipeptidyl peptidase-4, which rapidly
      inactivates/degrades the incretin hormones. The roles of the incretin hormones in
      the regulation of glucose metabolism and other related physiologic processes such
      as gut motility and food intake are disturbed in type 2 diabetes. These
      disturbances--defects in the incretin system--contribute to the pathophysiology
      of type 2 diabetes in manifold ways. Consequently, therapies designed to address
      impairments to the effects of the incretin hormones have the potential to improve
      glucose regulation and other abnormalities (e.g., weight gain, loss of beta-cell
      function) associated with type 2 diabetes.

PMID- 19580950
TI  - Efficacy and safety of incretin-based therapies in patients with type 2 diabetes
      mellitus.
AB  - This article aims to provide an overview of efficacy and safety data on glucagon
      like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4)
      inhibitors in the treatment of type 2 diabetes mellitus. Our goal is to
      differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4
      inhibitors, as well as the individual agents within each class. Additionally, we
      examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these
      agents may be applied at different stages of type 2 diabetes therapy and discuss
      recently published clinical findings and their implications for treatment.

PMID- 19580951
TI  - Incretin therapies: effects beyond glycemic control.
AB  - Impaired insulin secretion plays a major role in the pathogenesis of type 2
      diabetes mellitus, and progressive loss of beta-cell function is a
      pathophysiologic hallmark of type 2 diabetes. Recent science has elaborated on
      the role of the incretin hormones on beta-cell function and insulin secretion, as
      well as the role that incretin-based pharmacotherapies may have on glycemic
      control and beta-cell function, possibly altering the progressive loss of beta
      cell function and possibly reversing/halting disease progression. However,
      incretin-based therapies may also have benefits extending beyond glycemic control
      and insulin secretion. In this review we examine some of those "beyond-glycemic"
      benefits, including presentation of data on weight reduction, blood pressure
      lowering, beneficial changes in the lipid profile, and improvements in myocardial
      and endothelial function. We investigate how those effects may help ameliorate
      the cardiovascular burden in patients with diabetes.

PMID- 19580952
TI  - Clinical application of incretin-based therapy: therapeutic potential, patient
      selection and clinical use.
AB  - Incretin-based therapies address the progressive nature of type 2 diabetes
      mellitus, not only by addressing glucose control but also with weight-neutral
      (i.e., dipeptidyl peptidase-4 inhibitors sitagliptin and vildagliptin) and weight
      reducing effects (i.e., glucagonlike peptide-1 [GLP-1] receptor agonists
      exenatide and liraglutide). Preclinical data suggest that incretin-based
      therapies may also preserve beta-cell function, holding promise of a truly
      disease-modifying therapy. This article examines clinical trial data and accepted
      algorithms with a view toward elucidating the application of these agents in
      routine clinical practice. We propose a systematic approach to treatment,
      addressing (1) patient selection, (2) optimal treatment combinations, and (3)
      timing and guidance for both initiation and intensification of therapy. The GLP-1
      receptor agonists, for example, could be particularly beneficial in patients
      whose weight significantly increases cardiovascular risk. Early use of these
      agents may be effective in preventing diabetes in those at risk, or in halting or
      retarding disease progression in patients with frank diabetes. Additional
      clinical investigation will be required to test such hypotheses. Given the ever
      increasing incidence of diabetes worldwide, the link between obesity and the
      development of type 2 diabetes, and the need for more effective, weight-focused,
      convenient and sustainable treatments, the data from such studies will be
      invaluable to further clarify the role of the incretins in the management of
      patients with type 2 diabetes.

PMID- 19580953
TI  - X-ray phase-based imaging: the third wave.

PMID- 19580956
TI  - Telling about advances.

PMID- 19580954
TI  - Diffraction-enhanced imaging of musculoskeletal tissues using a conventional x
      ray tube.
AB  - RATIONALE AND OBJECTIVES: In conventional projection radiography, cartilage and
      other soft tissues do not produce enough radiographic contrast to be
      distinguishable from each other. Diffraction-enhanced imaging (DEI) uses a
      monochromatic x-ray beam and a silicon crystal analyzer to produce images in
      which attenuation contrast is greatly enhanced and x-ray refraction at tissue
      boundaries can be detected. The aim of this study was to test the efficacy of
      conventional x-ray tube-based DEI for the detection of soft tissues in
      experimental samples. MATERIALS AND METHODS: Cadaveric human tali (normal and
      degenerated) and a knee and thumb were imaged with DEI using a conventional x-ray
      tube and DEI setup that included a double-silicon crystal monochromator and a
      silicon crystal analyzer positioned between the imaged object and the detector.
      RESULTS: Diffraction-enhanced images of the cadaveric tali allowed the
      visualization of cartilage and its specific level of degeneration for each
      specimen. There was a significant correlation between the grade of cartilage
      integrity as assessed on the tube diffraction-enhanced images and on their
      respective histologic sections (r = 0.97, P = .01). Images of the intact knee
      showed the articular cartilage edge of the femoral condyle, even when
      superimposed by the tibia. In the thumb image, it was possible to visualize
      articular cartilage, tendons, and other soft tissues. CONCLUSION: DEI based on a
      conventional x-ray tube allows the visualization of skeletal and soft tissues
      simultaneously. Although more in-depth testing and optimization of the DEI setup
      must be carried out, these data demonstrate a proof of principle for further
      development of the technology for future clinical imaging.

PMID- 19580957
TI  - Human performance interfaces in air traffic control.
AB  - This paper examines how human performance factors in air traffic control (ATC)
      affect each other through their mutual interactions. The paper extends the
      conceptual SHEL model of ergonomics to describe the ATC system as human
      performance interfaces in which the air traffic controllers interact with other
      human performance factors including other controllers, software, hardware,
      environment, and organisation. New research hypotheses about the relationships
      between human performance interfaces of the system are developed and tested on
      data collected from air traffic controllers, using structural equation modelling.
      The research result suggests that organisation influences play a more significant
      role than individual differences or peer influences on how the controllers
      interact with the software, hardware, and environment of the ATC system. There
      are mutual influences between the controller-software, controller-hardware,
      controller-environment, and controller-organisation interfaces of the ATC system,
      with the exception of the controller-controller interface. Research findings of
      this study provide practical insights in managing human performance interfaces of
      the ATC system in the face of internal or external change, particularly in
      understanding its possible consequences in relation to the interactions between
      human performance factors.

PMID- 19580959
TI  - Body-related film clip triggers desire to binge in women with binge eating
      disorder.
AB  - Previous research suggests that excessive influence of shape or weight concern on
      self-evaluation is strongly associated with psychological functioning in women
      with binge eating disorder (BED). However, little is known so far about its
      direct influence on binge episodes. In an experimental study, 27 women with BED
      (DSM-IV) and 25 overweight healthy controls watched a body-related film clip.
      Ratings of the desire to binge and mood were assessed prior to and at the end of
      the film clip. Additionally, measures of heart rate, finger pulse and
      electrodermal activity were obtained. Main results revealed a significant
      increase in the desire to binge, sadness and anxiety, as well as a significant
      increase in non-specific skin conductance fluctuation on the body-related clip in
      the group of BED only. The results underline the importance of shape and weight
      concerns in BED.

PMID- 19580958
TI  - Influence of ADAM28 on biological characteristics of human dental follicle cells.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of a disintegrin
      and metalloproteinase 28 (ADAM28) on the biological characteristics of human
      dental follicle cells (HDFCs) and possible action mechanism. METHODS: Eukaryotic
      expression plasmid containing ADAM28 coding region and ADAM28 antisense
      oligodeoxynucleotides (AS-ODN) with FITC labelling were constructed and
      synthesised by gene clone and recombination. Then we respectively transfected
      them into HDFCs by Lipofectamine 2000 system and detected their effects on
      proliferation, differentiation and apoptosis of HDFCs by MTT assay, cell cycle
      detection, ALP activity and Annexin V-FITC/PI analysis. Finally we observed the
      effects of ADAM28 AS-ODN on HDFCs expressing extracellular matrix (ECM) proteins
      by immunocytochemical staining. RESULTS: ADAM28 eukaryotic plasmid was
      constructed and identified successfully, and could be correctly translated and
      expressed in HDFCs, furthermore overexpression of ADAM28 promoted the HDFCs
      proliferation and inhibited specific differentiation of HDFCs, while inhibition
      of ADAM28 exerted the opposite effects and induced apoptosis. Moreover ADAM28
      could significantly inhibit the secretion of OPN and type III collagen of HDFCs.
      CONCLUSIONS: ADAM28 might actively participate in the network regulation which
      associates HDFCs proliferation, differentiation, apoptosis with matrix
      mineralisation during tooth development by interacting with multiple signal
      molecules.

PMID- 19580960
TI  - Carers' attributions about positive events in psychosis relate to expressed
      emotion.
AB  - BACKGROUND: Relapse is increased in people with psychosis who live with carers
      with high expressed emotion (EE). Attributional style has been used to understand
      EE at a psychological level. Previous studies have investigated carer appraisals
      for negative events in the patient's life. We therefore aimed to examine
      spontaneous carer attributions for both negative and positive events. Further, we
      distinguished between high EE based on critical comments, and that based on
      emotional-overinvolvement. METHOD: Audiotapes of the Camberwell Family Interview
      (CFI) (N = 70) were rated using the Leeds Attributional Coding System (LACS).
      Raters were blind to previous ratings of EE. RESULTS: In our sample, low EE
      carers made significantly more attributions about positive events, and less about
      negative events than high EE carers. This is because criticism, but not
      overinvolvement, was strongly associated with responsibility attributions for
      negative events, while overinvolvement, but not criticism, was inversely
      associated with responsibility attributions for positive events. CONCLUSION:
      Carers' attributions for both positive and negative events may be a useful target
      for improving family interventions in psychosis.

PMID- 19580961
TI  - A self-organizing learning account of number-form synaesthesia.
AB  - Some people automatically and involuntarily "see" mental images of numbers in
      spatial arrays when they think of numbers. This phenomenon, called number forms,
      shares three key characteristics with the other types of synaesthesia, within
      individual consistency, between-individual variety, and mixture of regularity and
      randomness. A theoretical framework called SOLA (self-organizing learning account
      of number forms) is proposed, which explains the generation process of number
      forms and the origin of those three characteristics. The simulations replicated
      the qualitative properties of the shapes of number forms, the property that
      numbers are aligned in order of size, that discontinuity usually occurs at the
      point of carry, and that continuous lines tend to have many bends.

PMID- 19580962
TI  - Seizure characterisation using frequency-dependent multivariate dynamics.
AB  - The characterisation of epileptic seizures assists in the design of targeted
      pharmaceutical seizure prevention techniques and pre-surgical evaluations. In
      this paper, we expand on the recent use of multivariate techniques to study the
      cross-correlation dynamics between electroencephalographic (EEG) channels. The
      maximum overlap discrete wavelet transform (MODWT) is applied in order to
      separate the EEG channels into their underlying frequencies. The dynamics of the
      cross-correlation matrix between channels, at each frequency, are then analysed
      in terms of the eigenspectrum. By examination of the eigenspectrum, we show that
      it is possible to identify frequency-dependent changes in the correlation
      structure between channels which may be indicative of seizure activity. The
      technique is applied to EEG epileptiform data and the results indicate that the
      correlation dynamics vary over time and frequency, with larger correlations
      between channels at high frequencies. Additionally, a redistribution of wavelet
      energy is found, with increased fractional energy demonstrating the relative
      importance of high frequencies during seizures. Dynamical changes also occur in
      both correlation and energy at lower frequencies during seizures, suggesting that
      monitoring frequency-dependent correlation structure can characterise changes in
      EEG signals during these. Future work will involve the study of other large
      eigenvalues and inter-frequency correlations to determine additional seizure
      characteristics.

PMID- 19580963
TI  - Fenofibrate causes regression of endometriotic implants: a rat model.
AB  - Fenofibrate -a peroxisome proliferator-activated receptor-a agonist- is an
      angiostatic agent that is commonly used in human liver diseases, therefore it may
      interfere with the angiogenetic process required for endometriosis. In a rat
      endometriosis model, we demonstrated that peritoneal implant areas and vascular
      endothelial growth factor levels in the peritoneal flud were significantly
      decreased in high dose or low dose finofibrate and luprolide acetate treated
      groups compared to control.

PMID- 19580964
TI  - The insulin-resistant phenotype of polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the individual parameters included in the diagnosis of
      polycystic ovary syndrome (PCOS), and their impact on insulin sensitivity.
      DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynaecology,
      Copenhagen University Hospital, Hvidovre, Denmark. PATIENT(S): Sixty-one women;
      36 women with PCOS and 25 age- and weight-matched control women were
      investigated. INTERVENTION(S): Peripheral insulin sensitivity was evaluated by
      the hyperinsulinemic euglycemic clamp, glucose tolerance by an oral glucose
      tolerance test (OGTT), and ovarian morphology by transvaginal ultrasonography
      (TVS). MAIN OUTCOME MEASURE(S): The Rotterdam criteria were used for diagnosing
      PCOS, and hirsutism was evaluated by the Ferriman Gallwey score. Insulin
      sensitivity was calculated as the insulin sensitivity index, and whole body
      insulin sensitivity was assessed by the homeostatic model assessment insulin
      resistance (IR) index. RESULT(S): Multiple regression analysis showed that body
      mass index (BMI) and hirsutism were independent predictors of IR evaluated by
      insulin sensitivity index, whereas BMI, total T, and hirsutism were independent
      predictors of IR evaluated by the homeostatic model assessment IR index. We found
      no significant association between ovarian morphology and insulin sensitivity or
      between menstrual frequency and insulin sensitivity. CONCLUSION(S): The PCOS is
      associated with IR. Body mass index, hyperandrogenemia, and hyperandrogenism are
      independent predictors of low insulin sensitivity.

PMID- 19580965
TI  - Conception probabilities at different days of menstrual cycle in Chinese women.
AB  - OBJECTIVE: To investigate the conception probability among Chinese women. DESIGN:
      Prospective observational study. SETTING: Clinics in hospitals and family
      planning institutes in 10 provinces and cities. PATIENT(S): A total of 851
      healthy married women aged 18-35 years with normal menstrual cycles who wish to
      have babies and with no contraception. INTERVENTION(S): Urinary LH was measured
      around days of expected ovulation for 7 days. The Barrett and Marshall model was
      used for calculation of conception probabilities on each cycle day from day -5 to
      day +1 in women with multiple episodes of intercourse. MAIN OUTCOME MEASURE(S):
      Pregnancies in 1, 3, and >or=6 months. RESULT(S): A total of 851 women with 2,055
      cycles were analyzed. In 489 cycles there was only one episode of intercourse. A
      total of 601 pregnancies occurred. The conception probabilities from days in
      relation to ovulation -5 to +1 for a single episode of intercourse were 0.216,
      0.102, 0.236, 0.233, 0.388, 0.293, and 0.386, respectively, and for multiple
      episodes they were 0.254, 0.271, 0.293, 0.365, 0.315, and 0.284, respectively,
      with the peak value at day -1. Recalculation of the efficacy of emergency
      contraception with low-dose mifepristone with the present conception
      probabilities showed higher efficacy. CONCLUSION(S): Conception probabilities
      among Chinese women are different from those in the literature. Further
      comparative studies are needed to confirm an ethnic difference.

PMID- 19580967
TI  - Low AMH and GnRH-antagonist strategies.

PMID- 19580968
TI  - Incidence of traumatic long-bone fractures requiring in-hospital management: a
      prospective age- and gender-specific analysis of 4890 fractures.
AB  - BACKGROUND: Musculoskeletal trauma represents a considerable global health
      burden; however, reliable population-based incidence data are lacking. Thus, we
      prospectively investigated the age- and sex-specific incidence patterns of long
      bone fractures in a defined population. METHODS: A 4-year prospective study of
      all long-bone fractures in a defined Norwegian population was carried out. The
      demographic data, as well as data on fracture type and location and mode of
      treatment were collected using recognised classification (e.g., AO/OTA -
      Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association;
      Gustilo-Anderson (GA) for open fractures). Age- and sex-adjusted incidences were
      calculated using population statistics. RESULTS: During the study period, 4890
      long-bone fractures were recorded. The overall incidence per 100,000 per year was
      406 with a 95% confidence interval (95%CI) of 395-417. The age-adjusted incidence
      for those <16 years (339; 95%CI: 318-360) was lower than that for those >or=16
      years (427; 95%CI: 414-440). The overall male incidence (337; 95%CI: 322-355) was
      lower than the female (476; 95%CI: 459-493), but the male:female ratio was 2:1
      among those <50 years, and 1:3 in those >or=50 years. The upper limb fractures
      had an overall incidence of 159 (95%CI: 152-166), whereas the lower limb fracture
      incidence was 247 (95%CI: 238-256). Open fractures occurred in 3%, with an
      incidence of 13 (95%CI: 11-15). Paediatric fractures were more likely to be
      treated conservatively with only 8% requiring internal fixation, compared to 56%
      internal fixation in those >or=16 years of age. An increase in the use of angular
      stable plates occurred during the study period. CONCLUSION: This prospectively
      collected study of long-bone fractures in a defined population recognises age-
      and gender-specific fracture patterns. Boys predominate in the younger age group
      for which treatment is basically conservative. In the senior population, women
      and operative treatment predominate.

PMID- 19580969
TI  - Lumbosacral dislocation: a review of the literature and current aspects of
      management.
AB  - Lumbosacral fracture dislocation is a very rare lesion and was first described by
      Watson-Jones in 1940. Two anatomical classifications are described in the
      literature, all other reports are case presentations. This fracture type is
      characterised by an antero- or retrolisthesis or a lateral translation of the 5th
      lumbar vertebra in relation to the sacrum. Biomechanics are discussed
      controversially. Most patients suffer from a high energy trauma with concomitant
      severe injuries. There is a high rate of additional neurological deficits.
      Fractures of the transverse process are thought to be sentinel fractures. MRI and
      CT scans are essential to detect the whole extent of the lesion. Circumferential
      fusion is recommended by several authors to regain stability at the lumbosacral
      junction.

PMID- 19580970
TI  - Use of Sheng-Hua-Tang and health-related quality of life in postpartum women: a
      population-based cohort study in Taiwan.
AB  - BACKGROUND: Although Sheng-Hua-Tang (comprising Radix Angelicae Sinensis,
      Ligustici Rhizoma, Semen Persicae, Zingiberis Rhizoma and Glycyrrhizae Radix) use
      during the postpartum has been popular in Chinese communities over a long period,
      its benefits have not been evaluated in terms of its effects on the health
      related quality of life of postpartum women. OBJECTIVES: This study aims to
      explore the relation between different patterns of Sheng-Hua-Tang use and the
      health-related quality of life in postpartum women. DESIGN: A longitudinal birth
      cohort follow-up study. SETTINGS AND PARTICIPANTS: We used multistage stratified
      systematic sampling to recruit 24,200 pairs, postpartum women and newborns, from
      the Taiwan national birth register in 2005. A structured questionnaire was
      successfully administered to 87.8% of the sampled population. METHODS: Subjects
      underwent a home interview 6 months after their deliveries between June 2005 and
      July 2006. The Medical Outcomes Study 36-item Short-Form (SF-36) was used to
      measure the quality of life of the women with different patterns of Sheng-Hua
      Tang use. RESULTS: Compared with those who never used after delivery, the scores
      of role limitations due to physical health and emotional problems significantly
      increased in women who used Sheng-Hua-Tang within 1 month only but decreased in
      those who continuously used within 1 month and later. In addition, the scores of
      role limitations due to physical health and emotional problems significantly
      increased in women who used Sheng-Hua-Tang regardless of the frequency.
      CONCLUSIONS: Sheng-Hua-Tang use during the first month of the postpartum period
      may have a positive effect on women's health-related quality of life especially
      in terms of role limitations due to physical health and emotional problems.
      However, continuous use after the first month of the postpartum period might have
      a negative effect on women's quality of life. Further studies are needed to
      replicate the results and elucidate the causal relations.

PMID- 19580971
TI  - Ageing and cardiovascular responses to head-up tilt in healthy subjects.
AB  - OBJECTIVE: Ageing is associated with increased postural blood pressure changes
      and attenuated cardiovascular reactivity. As the background of these changes
      remains uncertain, we examined arterial stiffness, cardiac function and vascular
      resistance in healthy subjects in supine position and during orthostatic
      challenge. METHODS: Haemodynamics of 179 normotensive subjects (109 female and 70
      male, 21-59 years) were examined using continuous radial pulse wave analysis,
      whole-body impedance cardiography, and plethysmographic finger blood pressures.
      RESULTS: Both in supine position and during head-up tilt central and peripheral
      blood pressure and augmentation index (amplitude of the reflected pressure wave
      divided by pulse pressure) increased, and time of pulse wave reflection decreased
      with age. Supine pulse wave velocity progressively increased with age. There were
      only minor differences in supine and upright systemic vascular resistance,
      cardiac index, stroke index, and heart rate that were not systematically related
      to age. In regression analysis, the explanatory factors for a more pronounced
      decrease in central systolic blood pressure during the head-up tilt were in the
      age of 50-59 years, higher baseline pulse wave velocity and central systolic BP.
      None of the changes in other haemodynamic variables during tilt were related to
      age. CONCLUSION: As no systematic age-related differences were observed in
      cardiac function or vascular resistance, these results support the view that
      progressive reduction of large arterial compliance contributes to the exaggerated
      age-related decrease in central systolic blood pressure in response to head-up
      tilt.

PMID- 19580972
TI  - Shift work and subclinical atherosclerosis: recommendations for fatty liver
      disease detection.

PMID- 19580973
TI  - Sol-gel synthesis of macro-mesoporous titania monoliths and their applications to
      chromatographic separation media for organophosphate compounds.
AB  - We have developed a method of independently tailoring the macro- and mesoporous
      structures in titania (TiO2) monoliths in order to achieve liquid chromatographic
      separations of phosphorous-containing compounds. Anatase TiO2 monolithic gels
      with well-defined bicontinuous macropores and microstructured skeletons are
      obtained via the sol-gel process in strongly acidic conditions using
      poly(ethylene oxide) as a phase separator and N-methylformamide as a proton
      scavenger. Aging treatment of the wet gels in the mother liquor at temperatures
      of 100-200 degrees C and subsequent heat treatment at 400 degrees C allow the
      formation and control of mesoporous structures with uniform pore size
      distributions in the gel skeletons, without disturbing the preformed macroporous
      morphology. The monolithic TiO2 rod columns with bimodal macro-mesoporous
      structures possess the phospho-sensitivity and exhibit excellent chromatographic
      separations of phosphorus-containing compounds.

PMID- 19580974
TI  - Composition analysis of positional isomers of phosphatidylinositol by high
      performance liquid chromatography.
AB  - An HPLC-based method has been developed for composition analysis of six
      positional isomers of phosphatidylinositol (PI), of which the phosphatidyl group
      was connected to different positions of the myo-inositol moiety. The method
      employed a combination of two types of HPLC analyses. One was direct separation
      of the six PI isomers into four peaks of 1(3)-PI, 2-PI, 4(6)-PI and 5-PI on a
      normal-phase silica gel column. The second method was for the separations of 1-PI
      from 3-PI and 4-PI from 6-PI, which were not separable on the normal-phase
      column. This method involved conversion of PI isomers into pentakis-(R)-1
      phenylethylcarbamate (PEC) derivatives, which were separated on a reversed-phase
      column. Using the established method, positional specificity of several
      engineered phospholipases D in enzymatic synthesis of PI from myo-inositol and
      phosphatidylcholine was investigated. This was performed by analyzing the
      isomeric composition of PIs synthesized by the mutant enzymes. Among five mutant
      enzymes tested, two showed strong specificity to 1-OH, one showed moderate
      preference to 1-OH, one preferred 3-OH, and one showed broad specificity towards
      1-, 3-, 4- and 6-OH.

PMID- 19580975
TI  - A concise analysis of the effect of temperature and propanediol-1, 2 on Pluronic
      F127 micellization using isothermal titration microcalorimetry.
AB  - This article aims to explore the possibility of using isothermal titration
      microcalorimetry (ITC) for the investigation of F127 micellization and to study
      the effect of temperature and addition of propanediol-1,2 on F127 micellization
      behavior. From this work, ITC proved efficient to be used as a tool for the
      determination of the critical micellization concentration (CMC) and the enthalpy
      of micellization (DeltaH(mic)) of F127, from which the other thermodynamic
      parameters were calculated (free energy (DeltaG(mic)), entropy (DeltaS(mic)), and
      heat capacity of micellization (DeltaC(p,mic))). The micellization of F127 was
      confirmed to be a strongly endothermic process with predominance of hydrophobic
      interactions (TDeltaS(mic)>DeltaH(mic)) and the correlation of enthalpy and
      entropy of micelle formation exhibits an excellent linearity. The temperature
      dependence of F127 micellization was revealed by using ITC, since the CMCs values
      were, respectively, 0.197, 0.095, 0.085, and 0.079 mM for temperatures 28, 29,
      30, and 31 degrees C. Secondly, by the addition of propanediol-1,2 to the
      micellization medium containing 1.187 mM of F127, the CMC was shifted to lower
      values (0.095, 0.081, 0.077, 0.069 and 0.066 mM, respectively, for propanediol
      1,2 concentrations of 0%, 1.4%, 2.3%, 2.8%, and 3.7% w/v in the micellization
      medium). Finally, ITC was used as diagnostic tool with the aim of checking the
      reproducibility of the experiments independently on the kinetic and the dynamic
      aspects related to the micelle formation breakup. However, in this work we proved
      that the use of ITC for the determination of the CMC and thermodynamic parameters
      associated with F127 micellization is limited to a range of temperatures when
      sigmoidal curves were obtained.

PMID- 19580976
TI  - Formation conditions and stability of a toxic tridecameric Al polymer under a
      soil environment.
AB  - It is important to study the formation conditions and the stability of the
      tridecameric Al polymer (Keggin-type Al(13) polycation,
      [AlO(4)Al(12)(OH)(24)(H(2)O)(12)](7+), known as Al(13)) due to its strong
      toxicity to living organisms of a soil environment. In order to examine the pH
      range where toxic Al(13) can exist in aqueous solution, (27)Al NMR spectra for
      sample solutions containing Al(3+) ions with various pH (pH 3.5-6.1) were
      measured. The results show that the peak due to Al(13) (peak due to 4-coordinated
      Al around 63 ppm) appeared at pH 3.6-5.7 and the peak intensity was relatively
      high at pH 4.1-4.8, suggesting that Al(13) can be formed at pH 3.6-5.7, while it
      can exist dominantly at pH 4.1-4.8. It was also found that Al(13) can stably
      adsorb onto a chelate resin, Chelex 100, by weak electrostatic interaction. The
      Chelex 100, with iminodiacetate groups, served as a model compound for surfaces
      of microbes covered with carboxyl groups and for surfaces of soil particles
      covered with humic substances having many carboxyl groups. Additionally,
      decomposition of Al(13) did not occur even after adsorption, and its pH stability
      range was wide compared to that in aqueous solution.

PMID- 19580977
TI  - AgCl and Ag/AgCl hollow spheres based on self-assemblies of a multi-amine head
      surfactant.
AB  - A simple method for fabricating Ag/AgCl hollow spheres was developed by using a
      multi-amine head surfactant C18N3 as a soft template. After adding AgNO(3) to
      micelles of C18N3 dispersed in HCl solution, Ag/AgCl hollow spheres were formed
      with diameters ranging from 100 nm to 1200 nm which were a function of aging
      time. The mechanical strength of the formed spheres was found to be very good,
      probably due to the uniquely structured C18N3 surfactant as well as the
      reinforcement effect of Ag/AgCl on the NH(2) terminal groups. The active species
      on the surfaces of hollow spheres, Ag(+) and Cl(-), remained almost unchanged
      when exposed to natural daylight for more than 1 year, showing a very good
      stability against light and environmental reduction. However, the obtained Ag+
      species on the surface could be transformed into Ag(0) quickly with high yield
      (ca. 90%) under UV light irradiation. The transfer process was studied by EDX
      spectra at different irradiation times. Thus the Ag/AgCl hollow spheres may serve
      as useful precursors for many other noble metallic hollow spheres because Ag
      could be replaced by other noble metals such as Au and Pt with the aid of the
      galvanic replacement reaction.

PMID- 19580978
TI  - Facile synthesis of mesoporous SBA-15 silica spheres and its application for high
      performance liquid chromatography.
AB  - Micrometer-sized mesoporous SBA-15 silica spheres have been synthesized using
      triblock copolymer poly(ethyleneoxide)-block-poly(propyleneoxide)-block
      poly(ethyleneoxide) (EO(20)PO(70)EO(20)) as structure-directing agent with the
      assistance of 1,3,5-trimethylbenzene and KCl. By controlling the composition of
      synthesis gel, SBA-15 silica spheres with particle size in the range of 2-4.5
      microm could be facilely obtained. The obtained SBA-15 silica spheres were
      characterized by X-ray diffraction, scanning electron microscopy, and N(2)
      physisorption technique. Dimethyloctadecylchlorosilane modified mesoporous SBA-15
      silica with diameter of 4.5 microm was explored as stationary phase in high
      performance liquid chromatography, and its chromatographic characteristics for
      separation of some small molecules and relatively large bio-molecules have been
      studied.

PMID- 19580979
TI  - A spectroscopic investigation into the interaction between bile salts and insulin
      in alkaline aqueous solution.
AB  - The interaction of a bile salt, sodium deoxycholate, with insulin was
      investigated by ultraviolet derivative spectroscopy, fluorescence, circular
      dichroism and photon correlation spectroscopy. The results indicate that the
      conversion of insulin from a monomer to a dimer, tetramer, or hexamer occurs over
      a concentration range of 5.5x10(-2)-1.1x10(-1) mg/ml in alkaline solution in the
      absence of bile salts, and that insulin exists primarily as a hexamer complex
      above this concentration. Evidence is presented that bile salt-induced
      dissociation of insulin at a high concentration is driven by electrostatic
      repulsion and hydrophobic interaction resulting from bile salt binding, and
      occurs at a concentration lower than the critical micelle concentration of bile
      salts. We suggest that the interaction between insulin and the bile salt occurs
      by hydrophobic binding followed by a poorly cooperative binding process with an
      increasing concentration of bile salts. In addition, the bile salt binding to the
      surface of insulin alters not only the microenvironment around tyrosine residues
      but also the conformation of insulin to some degree, which probably resulted from
      the dissociation of insulin. However, no notable loss of structure happens to
      insulin during all the processes under our experimental conditions. A mechanism
      of bile salt binding to insulin and bile salt-mediated dissociation of insulin
      oligomers is proposed whereby hydrophobic interaction and electrostatic repulsion
      happen between them. This work also showed that the combination of these
      spectroscopic studies is a powerful tool to clarify the interactions between
      these surfactants and proteins.

PMID- 19580980
TI  - Phylogenetic distribution of virulence genes in Escherichia coli isolated from
      bovine mastitis in Iran.
AB  - One hundred and twenty seven Escherichia coli isolates from bovine mastitis were
      examined to detect the phylogenetic group/subgroups and a selection of virulence
      associated genes. Forty nine (38.58%) isolates belonged to group B1 the remaining
      isolates fell into four phylogenetic subgroups: A(0) (18.11%), A(1) (26.77%),
      D(1) (6.29%) and D(2) (10.23%). None of the isolates belonged to B2 group. Forty
      seven (37.00%) isolates were positive for at least one virulence gene, among them
      f17A was the most common gene, found in 20.47% of the isolates. Among the E. coli
      isolates, 11.81% had iucD, 9.44% f17c-A, 9.44% cnf2, 7.87% f17b-A, 6.29% afaD-8
      and afaE-8, 3.14% f17d-A, 0.78% cnf1 and 0.78% clpG genes. All of the detected
      virulence genes were present alone or in combination with each other except clpG
      and f17d-A genes that were only found alone. None of the isolates contained the
      genes for F17a-A, intimin, P or S fimbriae.

PMID- 19580981
TI  - Comparation of enhanced green fluorescent protein gene transfected and wild-type
      porcine neural stem cells.
AB  - The aim of this study was to transfect and express the enhanced green
      fluorescence protein (EGFP) gene into porcine neural stem cells (NSCs) to
      determine whether EGFP can be used as a marker to monitor NSCs. NSCs were
      isolated from embryonic day 30 fetal pig brain and transfected with EGFP gene
      using lipofection. Transfected and wild-type NSCs were induced to differentiate
      into cells of neuronal and myogenic lineages. Markers of passage three NSCs and
      their differentiated cells were tested by reverse transcription polymerase chain
      reaction. The results showed that EGFP could be expressed in NSCs and the
      differentiated cells. NSCs expressed Nestin, NogoA, DCX, Hes1, Oct4, CD-90 and
      Sox2. NSCs could differentiated into astrocyte (GFAP(+)), oligodendrocyte
      (GalC(+)), neuron (NF(+), NSE(+) and MAP2(+)) and myocyte (myf-6(+) and myoD(+)).
      We concluded that EGFP can be used as a marker in monitoring NSCs.

PMID- 19580982
TI  - Isolation and characterization of a new insect flavivirus from Aedes albopictus
      and Aedes flavopictus mosquitoes in Japan.
AB  - We isolated a new flavivirus from Aedes albopictus mosquito and a related species
      in Japan. The virus, designated Aedes flavivirus (AEFV), only replicated in a
      mosquito cell line and produced a mild cytopathic effect. The AEFV genome was
      positive-sense, single-stranded RNA, 11,064 nucleotides in length and contained a
      single open reading frame encoding a polyprotein of 3341 amino acids with 5' and
      3' untranslated regions (UTRs) of 96 and 945 nucleotides, respectively. Genetic
      and phylogenetic analyses classified AEFV with the insect flavivirus, but
      distinct from Cell fusing agent (CFA), Kamiti river virus and Culex flavivirus.
      Interestingly, a partial sequence of AEFV showed significant similarity to that
      of Cell silent agent (CSA), the insect flavivirus-related nucleotide sequence
      integrated in the genome of A. albopictus. These results suggest that AEFV is a
      new member of the insect flaviviruses, which are intimately associated with Aedes
      mosquitoes and may share a common origin with CSA.

PMID- 19580983
TI  - Host cell proteins interacting with the 3' end of TGEV coronavirus genome
      influence virus replication.
AB  - Coronavirus RNA synthesis is performed by a multienzymatic replicase complex
      together with cellular factors. This process requires the specific recognition of
      RNA cis-acting signals located at the ends of the viral genome. To identify
      cellular proteins involved in coronavirus RNA synthesis, transmissible
      gastroenteritis coronavirus (TGEV) genome ends, harboring essential cis-acting
      signals for replication, were used as baits for RNA affinity protein
      purification. Ten proteins were preferentially pulled down with either the 5' or
      3' ends of the genome and identified by proteomic analysis. Nine of them,
      including members of the heterogeneous ribonucleoprotein family of proteins
      (hnRNPs), the poly(A)-binding protein (PABP), the p100 transcriptional co
      activator protein and two aminoacyl-tRNA synthetases, showed a preferential
      binding to the 3' end of the genome, whereas only the polypyrimidine tract
      binding protein (PTB) was preferentially pulled down with the 5' end of the
      genome. The potential function of the 3' end-interacting proteins in virus
      replication was studied by analyzing the effect of their silencing using a TGEV
      derived replicon and the infectious virus. Gene silencing of PABP, hnRNP Q, and
      glutamyl-prolyl-tRNA synthetase (EPRS) caused a significant 2 to 3-fold reduction
      of viral RNA synthesis. Interestingly, the silencing of glyceraldehyde 3
      phosphate dehydrogenase (GAPDH), initially used as a control gene, caused a 2 to
      3-fold increase in viral RNA synthesis in both systems. These data suggest that
      PABP, hnRNP Q, and EPRS play a positive role in virus infection that could be
      mediated through their interaction with the viral 3' end, and that GAPDH has a
      negative effect on viral infection.

PMID- 19580984
TI  - Ozone-biological activated carbon as a pretreatment process for reverse osmosis
      brine treatment and recovery.
AB  - Ozonation was used in this study to improve biodegradability of RO brine from
      water reclamation facilities. An ozone dosage ranging from 3 to 10 mg O(3)/L and
      contact times of 10 and 20 min in batch studies were found to increase the
      biodegradability (BOD(5)/TOC ratio) of the RO brine by 1.8-3.5 times. At the same
      time, total organic carbon (TOC) removal was in the range of 5.3-24.5%. The lab
      scale ozone-biological activated carbon (BAC) at an ozone dosage of 6.0mg O(3)/L
      with 20-min contact time was able to achieve 3 times higher TOC removal compared
      to using BAC alone. Further processing with Capacitive Deionization (CDI) process
      was able to generate a product water with better water quality than the RO feed
      water, i.e., with more than 80% ions removal and a lower TOC concentration. The
      ozone-BAC pretreatment has the potential of reducing fouling in the CDI process.

PMID- 19580985
TI  - Treatment of oil well "produced water" by waste stabilization ponds: removal of
      heavy metals.
AB  - Oil well produced water (PW) can serve as an alternative water resource for
      restricted halotolerant agricultural purposes if the main pollutants,
      hydrocarbons and heavy metals, can be removed to below the irrigation standards.
      In this work, the potential removal of cadmium(II), chromium(III) and nickel(II)
      from PW by chemical precipitation in biological treatment was evaluated.
      Precipitation as a sulphide salt was found to be a very effective mechanism,
      which together with biosorption, biological metal uptake, precipitation as
      hydroxides and carbonates could remove heavy metals down to below irrigation
      standards. The existence and capability of these various mechanisms was
      demonstrated in the performance of a continuous artificial pond followed by
      intermittent sand filter, achieving removals of around 95% for nickel(II) and
      even higher removal rates for cadmium(II), chromium(III) from artificial PW after
      the installation of an anaerobic stage. The treated effluent quality was higher
      than that required by current European standards.

PMID- 19580986
TI  - Effects of hardness and alkalinity on the removal of arsenic(V) from humic acid
      deficient and humic acid-rich groundwater by zero-valent iron.
AB  - The effects of hardness (Ca(2+)) and alkalinity (HCO(3)(-)) on arsenic(V) removal
      from humic acid (HA)-deficient and HA-rich groundwater by zero-valent iron
      (Fe(0)) were investigated using batch experiments. Arsenic, in general, is
      removed from groundwater possibly by adsorption and co-precipitation with the
      iron corrosion products. However, in the co-presence of HCO(3)(-) and Ca(2+), the
      removal rate of arsenic increased with increasing concentrations of either Ca(2+)
      or HCO(3)(-). It was observed that the removal of arsenic was significantly
      enhanced by the formation of CaCO(3) as a nucleation seed for the growth of large
      iron (hydr)oxide particles. In the co-existence of Ca(2+), HCO(3)(-) and HA, the
      presence of HA diminished the positive role of Ca(2+) due to the formation of Fe
      humate complexes in solution and delaying of the formation of CaCO(3). As a
      result, the formation of the large iron (hydr)oxide particles was inhibited in
      the earlier stage which, in turn, affected the removal of arsenic. However, after
      the formation of CaCO(3) and the subsequent growth of such particles, the
      presence of large iron (hydr)oxide particles resulted in the rapid removing of
      arsenic and Fe-humate by adsorption and/or co-precipitation.

PMID- 19580987
TI  - Chemical changes in heavy metals in the leachates from Technosols.
AB  - A 2 month long column study was conducted to evaluate the mobility of heavy
      metals eluting from Technosols constituted from sewage sludges (aerobic or
      anaerobic) (as controls) or a mixture of different types of sewage sludges with
      green foundry sand (FS) or/and Linz-Donowitz slag (LD). The organic and inorganic
      wastes were mixed at a ratio of 56:44 (w/w). The mixtures and the controls were
      moistened to field capacity before adding them to the polypropylene columns (4.5
      cm wide and 14 cm long). During the 8-week experimental period, the columns were
      watered, twice a week, with 100 mL of deionised water. The concentrations of
      heavy metals (Cu, Zn, Ni, Pb, Cd, and Cr) in the leachates were determined
      periodically. The concentrations of all the heavy metals were generally higher in
      the leachates from the Technosols containing anaerobic sewage sludge as a
      component. The concentration of Cu was strongly dependent on pH and was
      significantly higher (P<0.05) in the most alkaline leachates (pH>10) than in the
      other leachates. More Zn was mobilized in the most acidic leachates (pH<6) than
      in other leachates. The concentration of Ni in 80% of the leachates exceeded the
      EU drinking water limit for Ni (0.02 mgL(-1)). The concentrations of Pb were
      lower in the Technosols containing FS. The concentrations of Cd in the leachates
      from Technosols containing the conditioners were relatively high, while
      concentrations of Cr were higher in the controls. As far as the potential
      toxicity of heavy metals is concerned, the combination of aerobic sludge,
      inorganic conditioners able to buffer the pH to around neutrality, and reactive
      aluminosilicates, can be regarded as suitable choice for formulating Technosols
      from wastes.

PMID- 19580988
TI  - Acute and chronic effects of nano- and non-nano-scale TiO(2) and ZnO particles on
      mobility and reproduction of the freshwater invertebrate Daphnia magna.
AB  - Among the emerging literature addressing the biological effects of nanoparticles,
      very little information exists, particularly on aquatic organisms, that evaluates
      nanoparticles in comparison to non-nanocounterparts. Therefore, the potential
      effects of nano-scale and non-nano-scale TiO(2) and ZnO on the water flea,
      Daphnia magna, were examined in 48-h acute toxicity tests using three different
      test media, several pigment formulations--including coated nanoparticles--and a
      variety of preparation steps. In addition, a 21-d chronic Daphnia reproduction
      study was performed using coated TiO(2) nanoparticles. Analytical
      ultracentrifugation analyses provided evidence that the nanoparticles were
      present in a wide range of differently sized aggregates in the tested
      dispersions. While no pronounced effects on D. magna were observed for nano-scale
      and non-nano-scale TiO(2) pigments in 19 of 25 acute (48-h) toxicity tests
      (EC50>100 mg L(-1)), six acute tests with both nano- and non-nano-scale TiO(2)
      pigments showed slight effects (EC10, 0.5-91.2 mg L(-1)). For the nano-scale and
      non-nano-scale ZnO pigments, the acute 48-h EC50 values were close to the 1 mg L(
      1) level, which is within the reported range of zinc toxicity to Daphnia. In
      general, the toxicity in the acute tests was independent of particle size (non
      nano-scale or nano-scale), coating of particles, aggregation of particles, the
      type of medium or the applied pre-treatment of the test dispersions. The chronic
      Daphnia test with coated TiO(2) nanoparticles demonstrated that reproduction was
      a more sensitive endpoint than adult mortality. After 21d, the NOEC for adult
      mortality was 30 mg L(-1) and the NOEC for offspring production was 3 mg L(-1).
      The 21-d EC10 and EC50 values for reproductive effects were 5 and 26.6 mg L(-1),
      respectively. This study demonstrates the utility of evaluating nanoparticle
      effects relative to non-nano-scale counterparts and presents the first report of
      chronic exposure to TiO(2) nanoparticles in D. magna.

PMID- 19580989
TI  - Temporal trends in the bioaccumulation of trace metals in herring, sprat, and cod
      from the southern Baltic Sea in the 1994-2003 period.
AB  - This study is based on raw data obtained from 1 225 samples of herring (Clupea
      harengus), sprat (Sprattus sprattus), and cod (Gadus morhua) collected in the
      1994-2003 period from the Polish coastal zone of the Baltic Sea. This paper
      presents the results of investigations of the contents of Cu, Zn, Cd, Pb, Hg, and
      As in fish. The aim was to identify temporal trends in trace metal contamination
      and variations in the concentrations of Hg in the flesh of herring, sprat, and
      cod of different lengths. A positive correlation between fish length and Hg
      concentration was noted for cod, sprat, and herring. The temporal trend analyses
      of heavy metal concentrations in the fish in the 1994-2003 period indicated ten
      significant downward trends out of eighteen tests; these referred to
      concentrations of Cd, Hg, and Pb in all the species studied, and to As in sprat.
      Concentrations of Cu and Zn remained stable in all the species studied, as did As
      in herring and cod. No upward trends were detected in the concentration of trace
      metals in the fish studied. Smaller scale temporal variations in concentrations
      of some elements were also observed and were associated with natural events, such
      as increased river discharge resulting from floods. The most likely factors which
      contributed to the observed downward trends in heavy metals concentrations in
      fish could possibly stem from lesser quantities of Cd, Pb, and Hg being
      introduced to the Baltic Sea with the waters of rivers from Baltic countries,
      including Poland, and atmospheric depositions in the 1994-2003 period.
      Diminishing trends of concentrations of these elements in Baltic Sea waters are
      also evidence of this. These facts might indicate that advantageous changes are
      occurring in the concentrations of heavy metals in the southern Baltic
      environment.

PMID- 19580990
TI  - Effects of low concentrations of the phenylurea herbicide diuron on biofilm algae
      and bacteria.
AB  - A system of recirculating channels was used in this study to examine the long
      term effects (29d) of environmentally realistic concentrations of the herbicide
      diuron (from 0.07 to 7 microg L(-1)) on biofilm communities. The autotrophic
      activity of biofilms was affected by this herbicide, as reflected by a marked
      decrease in the photosynthetic efficiency. Diuron exposure also increased
      chlorophyll-a content and reduced the biovolume of diatom taxa at low
      concentrations. The effects on bacteria were also remarkable. Bacterial abundance
      was reduced after a week of exposure to the herbicide at a range of
      concentrations. Effects were on the number of live bacteria and on the increase
      in the leucine-aminopeptidase activity. It is suggested that inputs of herbicides
      to the river ecosystem at low concentrations may cause a chain of effects in the
      biofilm, which include inhibitory effects on algae but also indirect effects on
      the relationships between biofilm components.

PMID- 19580991
TI  - Stereospecific degradation of phenylsuccinate by actinomycetes.
AB  - Racemic phenylsuccinate was stereospecifically degraded by the actinomycetes PS9
      and PS17 isolated from soil obtained from Okinawa Island, Japan. Strain PS9,
      identified as a Citricoccus sp., preferentially degraded the R-form, while strain
      PS17, identified as a Microbacterium sp., preferentially degraded the S-form of
      phenylsuccinate. Analysis of the culture broths of these species with
      phenylsuccinate as the sole carbon source revealed that benzoic acid was produced
      as a metabolic intermediate. Benzoic acid was further degraded by strain PS9 with
      m- and/or p-hydroxybenzoic acid but not o-hydroxybenzoic acid as possible
      intermediates.

PMID- 19580992
TI  - Dominance of dietary intake of metals in marine elasmobranch and teleost fish.
AB  - Metal accumulation in marine fish is a global public health concern, because the
      consumption of seafood provides the largest dose of many toxic metals to humans.
      While water quality criteria often rely on aqueous exposures of metals to fish in
      developing safety guidelines, it is increasingly recognized that marine fish
      obtain an important fraction of their metal body burden from their diet. Using
      experimental data, we modeled the accumulation of six metals (Am, Cd, Cs, Co, Mn,
      Zn) from diet and from the aqueous phase in two marine fish species, the teleost
      Psetta maxima and elasmobranch Scyliorhinus canicula. We estimated steady-state
      metal concentrations and calculated the relative contributions of dietary and
      aqueous intake in both species. For both species >60% and often >90% of Mn, Cd,
      and Zn derives from dietary intake in these species, even at the lowest ingestion
      rates reported for these fish. At low ingestion rates, Am was obtained
      predominantly from the aqueous phase and Cs varied considerably depending on prey
      selection. Inter-specific differences were noted, especially in Co uptake. Model
      predictions of steady-state tissue metal concentrations are within the range of
      field measurements for these species. Our findings underscore the importance of
      including dietary exposure in understanding metal accumulation in marine fish.

PMID- 19580994
TI  - Effects of local point source polychlorinated biphenyl (PCB) contamination on
      bone mineral density in deer mice (Peromyscus maniculatus).
AB  - A former local source of PCBs has contaminated soil and the terrestrial food web
      at Saglek, Labrador. The relationship between PCB exposure and bone mineral
      density as an osteoporosis biomarker in deer mice (Peromyscus maniculatus) was
      investigated at two sites at Saglek: a contaminated Beach and a reference area.
      Bone mineral density was measured on the femur of twenty-six deer mice using dual
      energy X-ray absorptiometry (DXA) technology. Bone mineral density was
      significantly lower in deer mice from the high exposure site (average whole body
      summation operatorPCB=5769 ng/g wet weight, n=20) than at the reference site
      (average whole body summation operatorPCB=79.8 ng/g wet weight, n=7). We used T
      scores from the World Health Organization to determine the degree of decreased
      bone mineral density in exposed mice. Assuming the same biomechanical forces
      apply as for humans, and using a conservative factor of 1.5 (fracture risk
      increases 1.5 to 3 fold for every standard deviation decrease in bone mineral
      density), mice from the contaminated Beach are up to five folds more susceptible
      to fracture risk than mice from the reference area. Therefore, the PCB
      concentrations found locally at contaminated military sites such as Saglek are
      high enough to affect local wildlife.

PMID- 19580995
TI  - Birth of viable puppies derived from breeding cloned female dogs with a cloned
      male.
AB  - Since the establishment of production of viable cloned dogs by somatic cell
      nucleus transfer, great concern has been given to the reproductive abilities of
      these animals (Canis familiaris). Therefore, we investigated reproductive
      activity of cloned dogs by (1) performing sperm analysis using computer-assisted
      sperm analysis and early embryonic development, (2) assessing reproductive
      cycling by measuring serum progesterone (P4) levels and performing vaginal
      cytology, and (3) breeding cloned dogs using artificial insemination. Results
      showed that most parameters of sperm motility in a cloned male dog were within
      the reference range, and in vivo-matured oocytes from a noncloned female were
      successfully fertilized by spermatozoa from a cloned male dog and develop
      normally to the 8-cell stage. Three cloned female dogs displayed normal patterns
      of P4 levels and morphologic changes of the vaginal epithelium. Two cloned female
      dogs became pregnant using semen from a cloned male dog and successfully
      delivered 10 puppies by natural labor. In conclusion, these data demonstrated
      that both cloned male and female dogs are fertile, and their puppies are
      currently alive and healthy with normal growth patterns.

PMID- 19580996
TI  - Effect of the amount of 3-methacyloxypropyltrimethoxysilane coupling agent on
      physical properties of dental resin nanocomposites.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of the amount of
      3-methacryloxypropyl-trimethoxysilane (gamma-MPS) coupling agent on some physical
      mechanical properties of an experimental resin composite for understanding the
      optimum amount of silanization. METHODS: Silica nanoparticles (Aerosil OX 50)
      used as filler were silanized with 5 different amounts of gamma-MPS 1.0, 2.5,
      5.0, 7.5 and 10 wt% relative to silica. The silanizated silica nanoparticles were
      identified by FT-IR spectroscopy and thermogravimetric analysis (TGA). Then the
      silanized nanoparticles (60 wt%) were mixed with a Bis-GMA/TEGDMA (50/50 wt/wt)
      matrix. Degree of conversion of light cured composites was determined by FT-IR
      analysis. The static flexural strength and flexural modulus were measured using a
      three-point bending set up. The dynamic thermomechanical properties were
      determined by DMA analyzer. Sorption, solubility and volumetric change were
      determined after storage of composites in water or ethanol/water solution.
      Thermogravimetric analysis was performed in air and in nitrogen atmosphere from
      50 to 800 degrees C. RESULTS: At lower silane amounts used (1.0, 2.5 wt%) the
      silane molecules must have a parallel orientation relative to the silica surface.
      At higher silane amounts (>2.5 wt%) silane molecules form a layer around the
      filler particles which now have to occupy a random, parallel and perpendicularly
      orientation relative to the silica surface. No significant statistic difference
      was found to exist between the flexural strength and flexural modulus values of
      composites with different silane contents. Dynamic elastic modulus E' showed a
      maximum value for the composite contained 5 wt% silane. The composites with the
      higher amounts of silane showed the lower values for the tandelta at the T(g)
      revealing that these composites have better interfacial adhesion between filler
      and matrix. SIGNIFICANCE: The amount of silane used for the silanization of
      silica particles affect the orientation of the silane molecules relative to the
      silica surface. This seems to affect the dynamic mechanical properties of
      composites.

PMID- 19580998
TI  - Depletion of peripheral blood B cells with Rituximab and phenotype
      characterization of the recovering population in a patient with follicular
      lymphoma.
AB  - The monoclonal antibody Rituximab is useful for treatment of patients with B-cell
      non-Hodgkin's lymphoma. We phenotypically analyzed reconstitution of peripheral B
      cells in a male patient with follicular lymphoma following their depletion with
      Rituximab. CD19+ and CD20+ B cell counts in peripheral blood decreased rapidly
      following Rituximab treatment. Six months after the end of treatment, a few CD19+
      B cells were detected in peripheral blood. These cells had a naive B cell
      phenotype (IgD+, CD27-) and they expressed high levels of CD38 and CD24, which
      show that the B cell pool was repopulated mainly with immature, naive B cells.

PMID- 19580997
TI  - Response to treatment in women with chronic myeloid leukemia during pregnancy and
      after delivery.
AB  - Here we report response to treatment of chronic myeloid leukemia (CML) of five
      pregnant women during and after pregnancy. CML was diagnosed during pregnancy in
      three patients. Pregnancy was confirmed during CML in two patients: in one in the
      21st week of pregnancy while on imatinib, in another in the 12th week during the
      interferon treatment. Interferon with leukapheresis when needed was applied in
      the 2nd and 3rd trimester. All patients except one achieved complete
      hematological response during pregnancy. After delivery four patients achieved
      partial cytogenetic response on imatinib and two patients achieved major
      molecular response after crossover to dasatinib.

PMID- 19580999
TI  - Successful imatinib mesylate therapy for acquired von Willebrand syndrome in
      chronic myelogenous leukemia.

PMID- 19581000
TI  - High incidence of chronic lymphocytic leukemia (CLL) diagnosed by
      immunophenotyping: a population-based Canadian cohort.
AB  - Incidence and outcomes of chronic lymphocytic leukemia/small lymphocytic lymphoma
      (CLL) are not well established at the population level, especially since the
      widespread use of immunophenotyping. We studied the epidemiology of CLL in
      Manitoba (Canada) by combining data from a centralized flow cytometry facility
      and the provincial cancer registry for the period 1998-2003. Of 616 cases
      identified, 27% of patients identified by flow cytometry were not on the cancer
      registry. The age-adjusted incidence of 7.99/100,000 is substantially higher than
      the reported incidence in registry reports. We also noted differences in relative
      survival based on age and gender.

PMID- 19581001
TI  - Change trajectories for parent-child interaction sequences during parent-child
      interaction therapy for child physical abuse.
AB  - OBJECTIVE: Parent-child interaction therapy (PCIT) has been found to reduce
      future child abuse reports among physically abusive parents. Reductions in
      observed negative parenting behaviors mediated this benefit. The current study
      examined session-by-session interaction sequences in order to identify when
      during treatment these changes occur and how much the trajectory varies from case
      to-case. METHOD: Session-by-session parent-child interaction sequences, using the
      Dyadic Parent-Child Interaction Coding System-II (DPICS-II) categories, were
      coded for 22 child welfare involved parent-child dyads undergoing PCIT for child
      physical abuse. A total 5,436 interactions across PCIT were coded and analyzed
      using growth curve analysis. RESULTS: At pre-treatment baseline, negative and
      positive parental responses were about equally likely to follow a child positive
      behavior. This pattern changed rapidly during PCIT, with rapid increases in
      positive parental responses and decreases in negative parental responses to
      appropriate child behavior. A quadratic growth pattern accounted for 70% of
      observed variance and virtually all change occurred during the first three
      sessions. CONCLUSION: Changes in observed abusive parent-abused child interaction
      patterns can occur early in PCIT, a parenting intervention that involves direct
      coaching and practice of skills. These benefits sustained throughout treatment.
      PRACTICE IMPLICATION: Prior to receiving behavioral parent training (PCIT),
      parents who have physically abused their children failed to match their parental
      response to their children's behavior. This pattern of interaction improved
      rapidly and substantially during the first three sessions of PCIT. The changes in
      the patterns of interaction also remained relatively stable for the remainder of
      treatment while parents continued to practice positive parental responses as well
      as began practicing effective discipline techniques. This suggests that use of
      immediate parent feedback through coaching, explicit directions to parents in how
      to respond to child behavior, and customization of the application of skills to
      the problems that arise in session are important components to effective
      parenting programs with physically abusive parents. Targeting these behaviors
      with PCIT has been found to reduce rates of recidivism, further supporting
      clinical application of PCIT in these cases.

PMID- 19581002
TI  - Using the Delphi method to engage stakeholders: a comparison of two studies.
AB  - Involving stakeholders can greatly impact evaluation results. The Delphi method,
      a consensus-building tool, is a promising process to promote and encourage
      involvement from all stakeholders during the evaluation framing process. The
      Delphi method removes geographic challenges and time boundaries allowing all
      stakeholders to participate. The Delphi method uses a series of surveys
      interspersed with controlled feedback designed to gather information and build
      consensus without requiring face-to-face meetings. Two different formats of the
      Delphi method, a paper-and-pencil, postal-mail version and a web-based, real-time
      computer version are compared in this study. Both versions of the Delphi were
      administered to a non-profit community based organization as part of framing an
      evaluation. Participation rates were better with the paper-pencil version. The
      quantity and quality of data collected were comparable in both versions.

PMID- 19581003
TI  - Correcting serum concentrations of organochlorine compounds by lipids:
      alternatives to the organochlorine/total lipids ratio.
AB  - INTRODUCTION: When studying the effects of organochlorine compounds (OCs) on
      human health it is common to correct serum concentrations of OC by total lipids
      (TL). However, the relationship between serum OCs and serum TL is far from
      established in many diseases, including several cancers. Our aim was to analyze
      the relationship between serum OC and TL in patients with pancreatic ductal
      adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid
      correction. METHODS: Incident cases of PDA were interviewed and had blood drawn
      soon around hospital admission (n=144). Serum concentrations of OCs were analysed
      by high-resolution gas chromatography with electron-capture detection. RESULTS:
      Most patients with high TL had moderate or low concentrations of OCs. By
      contrast, the variability of OC values among patients with normal TL was large.
      Correlations were of a similar magnitude between OC and TL and between OC and
      total cholesterol; while these correlations were weak (all Spearman's rho<0.3 and
      R(2)<0.11), no OC were significantly correlated with triglycerides. Although all
      alternatives to the OC/TL linear ratio were statistically significant for at
      least one OC, their R(2) was always below 10%. CONCLUSIONS: In patients with
      severe diseases as PDA, linear correction of OC by TL as commonly performed in
      epidemiologic studies may be inappropriate. Results contribute to the scant
      literature on the rationale to correct serum concentrations of OC by lipids. They
      suggest that it is unwarranted to routinely correct OC by TL, offer ways to
      assess such need, and present alternatives as no TL correction, correction by
      total cholesterol only or use of different statistical models.

PMID- 19581004
TI  - Production of house finch (Carpodacus mexicanus) IgA specific anti-sera and its
      application in immunohistochemistry and in ELISA for detection of Mycoplasma
      gallisepticum-specific IgA.
AB  - The IgA antibody response plays a vital role in mucosal immunity because it
      functions to neutralize pathogens at the mucosal surface and thus impedes
      attachment to underlying tissues. Although the importance of IgA in the mucosal
      immunity of galliform birds has been established, studies examining IgA-based
      immunity in passerine birds are lacking, perhaps due in part to the absence of
      reagents that can detect passerine IgA. A 469 base pair region of the house finch
      (Carpodacus mexicanus) IgA heavy chain was PCR-amplified from spleen cDNA and
      sequenced. The predicted amino acid sequence was found to share 55% and 46%
      identity with the IgA heavy chain of mallard (Anas platyrhynchos) and chicken
      (Gallus gallus), respectively. The heavy chain fragment was produced using a
      bacterial expression system and purified. Rabbit anti-sera were generated against
      the recombinant protein. The anti-sera reacted with a single house finch serum
      protein ( approximately 50-55kDa) in Western blot. The anti-sera were used to
      identify plasma cells in the Harderian gland and conjunctiva of house finches
      with conjunctivitis associated with Mycoplasma gallisepticum infection. The anti
      sera were also utilized in an ELISA to detect M. gallisepticum-specific IgA
      antibodies in lachrymal samples of infected finches.

PMID- 19581005
TI  - Intranasal vaccination of calves with Mannheimia haemolytica chimeric protein
      containing the major surface epitope of outer membrane lipoprotein PlpE, the
      neutralizing epitope of leukotoxin, and cholera toxin subunit B.
AB  - This study was done to determine if intranasal vaccination of weaned beef calves
      with a chimeric protein containing the immunodominant surface epitope of
      Mannheimia haemolytica PlpE (R2) and the neutralizing epitope of leukotoxin
      (NLKT) covalently linked to truncated cholera toxin (CT) subunit B (CTB) could
      stimulate secretory and systemic antibodies against M. haemolytica while
      enhancing resistance of cattle against M. haemolytica intrabronchial challenge.
      Sixteen weaned beef calves were intranasally vaccinated with CTB-R2-NLKT chimeric
      (SAC102) or with R2-NLKT-R2-NLKT chimeric (SAC89) protein with or without native
      CT on days 0 and 14 and were challenged intrabronchially on day 28. In vitro,
      SAC102 bound the CT receptor molecule, GM(1)-ganglioside. Mean IgA antibodies to
      M. haemolytica whole cells (WC) and to LKT were high on day 0. A small, yet
      significant increase (p<0.05) was found in mean nasal antibodies to M.
      haemolytica WC for the SAC89+CT and SAC102 vaccinates after the second
      vaccination. SAC102 stimulated significant (p<0.05) mean serum antibody responses
      to all three antigens by day 28. Following challenge, mean antibodies to WC and
      LKT significantly increased (p<0.05) for the SAC102, SAC89 and SAC89+CT groups
      with the mean antibody responses to rPlpE stimulated by SAC102 vaccination being
      significantly higher (p<0.05) than for the other vaccinated and control groups.
      On day 1 after challenge, mean clinical score for the control group was
      significantly higher (p<0.05) than for the SAC102 and SAC89+CT vaccinates, and by
      day 2 after challenge, clinical score for the control group was significantly
      higher (p<0.05) than for all three chimeric vaccinated groups. Therefore,
      intranasal vaccination with CTB-R2-NLKT (SAC102) and R2-NLKT-R2-NLKT (SAC89)
      chimeric proteins enhanced resistance against intrabronchial challenge with the
      bacterium as well as stimulating antibody responses to M. haemolytica antigens.

PMID- 19581006
TI  - Health-related quality of life of adolescents with childhood diagnosis of
      specific language impairment.
AB  - OBJECTIVE: To evaluate the health-related quality of life (HRQoL) of adolescents
      with a diagnosis of specific language impairment (SLI). METHODS: A clinical
      sample of 67 subjects with a childhood diagnosis of SLI, now aged 12-16, were
      asked to fill out the generic 16D HRQoL questionnaire. The comparison group
      comprised 235 typically developing peers. Another questionnaire gathered
      information about school and rehabilitation. RESULTS: Of the surveyed 73%
      answered; 77% were male. Total HRQoL score between subjects and controls did not
      differ. The group profiles had some differences. The SLI group experienced more
      problems in the dimension of mental functioning (p=0.001), whereas the control
      group was worse off on the dimension vitality (p=0.003). In the SLI group, low
      vitality was related to low verbal IQ in childhood, and own perception of
      literacy problems. Long-term speech therapy was associated with problems in the
      dimension of speech. CONCLUSIONS: The overall HRQoL of adolescents with SLI was
      at age-level, but language-related problems seemed to lead to increased problems
      in mental functioning. Low vitality was more of a problem for the controls, but
      also for those SLI children who had inferior language performance. Adolescents'
      own perceptions of their life quality are of clinical importance, and 16D seems a
      usable tool to capture them.

PMID- 19581007
TI  - Understanding speech in noise after correction of congenital unilateral aural
      atresia: effects of age in the emergence of binaural squelch but not in use of
      head-shadow.
AB  - OBJECTIVE: Unilateral hearing loss causes difficulty hearing in noise (the
      "cocktail party effect") due to absence of redundancy, head-shadow, and binaural
      squelch. This study explores the emergence of the head-shadow and binaural
      squelch effects in children with unilateral congenital aural atresia undergoing
      surgery to correct their hearing deficit. Adding patients and data from a similar
      study previously published, we also evaluate covariates such as the age of the
      patient, surgical outcome, and complexity of the task that might predict the
      extent of binaural benefit--patients' ability to "use" their new ear--when
      understanding speech in noise. METHODS: Patients with unilateral congenital aural
      atresia were tested for their ability to understand speech in noise before and
      again 1 month after surgery to repair their atresia. In a sound-attenuating booth
      participants faced a speaker that produced speech signals with noise 90 degrees
      to the side of the normal (non-atretic) ear and again to the side of the atretic
      ear. The Hearing in Noise Test (HINT for adults or HINT-C for children) was used
      to estimate the patients' speech reception thresholds. The speech-in-noise test
      (SPIN) or the Pediatric Speech Intelligibility (PSI) Test was used in the
      previous study. RESULTS: There was consistent improvement, averaging 5dB
      regardless of age, in the ability to take advantage of head-shadow in
      understanding speech with noise to the side of the non-atretic (normal) ear.
      There was, in contrast, a strong negative linear effect of age (r(2)=.78,
      selecting patients over 8 years) in the emergence of binaural squelch to
      understand speech with noise to the side of the atretic ear. In patients over 8
      years, this trend replicated over different studies and different tests. Children
      less than 8 years, however, showed less improvement in the HINT-C than in the PSI
      after surgery with noise toward their atretic ear (effect size=3). No binaural
      result was correlated with degree of hearing improvement after surgery.
      CONCLUSIONS: All patients are able to take advantage of a favorable signal-to
      noise ratio in their newly opened ear; that is with noise toward the side of the
      normal ear (but this physical, bilateral, head-shadow effect need not involve
      true central binaural processing). With noise toward the atretic ear, the
      emergence of binaural squelch replicates between two studies for all but the
      youngest patients. Approximately 2dB of binaural gain is lost for each decade
      that surgery is delayed, and zero (or poorer) binaural benefit is predicted after
      38 years of age. Older adults do more poorly, possibly secondary to their long
      period of auditory deprivation. At the youngest ages, however, binaural results
      are different in open- and closed-set speech tests; the more complex hearing
      tasks may involve a greater cognitive load. Other cognitive abilities (late
      evoked potentials, grey matter in auditory cortex, and multitasking) show similar
      effects of age, peaking at the same late-teen/young-adult period. Longer follow
      up is likely critical for the understanding of these data. Getting a new ear may
      be--like multitasking--challenging for the youngest and oldest subjects.

PMID- 19581008
TI  - Differential responses to copper-induced oxidative stress in the marine
      macroalgae Lessonia nigrescens and Scytosiphon lomentaria (Phaeophyceae).
AB  - In order to help explain the absence of the brown kelp Lessonia nigrescens from a
      coastal environment chronically enriched with copper, we characterized the
      biochemical responses induced by copper stress in this kelp and compared them
      with those displayed by the copper tolerant brown alga Scytosiphon lomentaria.
      These algae were cultivated with increasing concentrations of copper (20, 40 and
      100microgL(-1)) for 96h and the temporal production of hydrogen peroxide,
      superoxide anions and lipoperoxides as well as the activities of antioxidant
      enzymes catalase (CAT), glutathione peroxidase (GP), ascorbate peroxidase (AP),
      dehydroascorbate reductase (DHAR) and glutathione reductase (GR) and the activity
      of the defense enzyme lipoxygenase (LOX) were determined. In L. nigrescens and S.
      lomentaria, a single peak of hydrogen peroxide was detected, with similar maxima
      after 3h of copper exposure, although in L. nigrescens buffering took longer.
      Superoxide anions, on the other hand, were only detected in L. nigrescens. The
      production of lipoperoxides in L. nigrescens increased steadily at higher copper
      levels, in a pattern clearly different to their rapid stabilization in S.
      lomentaria. We suggest that the accumulation of lipoperoxides might be related to
      LOX, whose activity also increases with exposure time. Furthermore, activities of
      the antioxidant enzymes CAT, GP, AP and DHAR were lower in L. nigrescens than in
      S. lomentaria, and GP and DHAR were completely inhibited at higher copper
      concentrations. Since these enzymes also detoxify fatty acid hydroperoxides,
      their inhibition, together with the activation of LOX, may explain the persistent
      and copper-dependent levels of lipoperoxides in L. nigrescens. Based on
      terrestrial plant models demonstrating toxic effects of lipoperoxides, and on our
      results on organellar ultrastructural changes, we suggest that copper toxicity
      induced an uncontrolled lipoperoxide accumulation which may lead to cell damage
      and dysfunction in L. nigrescens, explaining at least partially, the absence of
      this kelp in a copper-enriched coastal environment.

PMID- 19581009
TI  - Lamotrigine-trigged obstructive hypertrophic cardiomyopathy, epilepsy and
      metabolic myopathy.
AB  - Lamotrigine has the advantage to have an antidepressive effect and to be well
      tolerated in the majority of the cases. Lamotrigine, however, may exert cardiac
      side effects in patients with hypertrophic cardiomyopathy and latent obstruction
      of the left ventricular outflow tract, as illustrated by the following case
      report. In a 67 year-old male with epilepsy, metabolic myopathy and malignant
      hyperthermia hypertrophic cardiomyopathy was diagnosed by echocardiography. By
      Doppler-echocardiography the maximal gradient in the left ventricular outflow
      tract was 57 mm Hg. Because or recurrent seizures, the lamotrigine dosage was
      increased from 100 mg/d to 200 mg and then to 300 mg/d. After the first intake of
      300 mg lamotrigine, the patient felt weak, dizzy and complained about exertional
      dyspnoea and chest pain. Doppler-echocardiography showed now a maximal gradient
      of 106 mm Hg in the left ventricular outflow tract. After reducing the
      lamotrigine dosage to 100 mg/d and adding levetirazetam (1000 mg/d), the
      patient's condition improved immediately and the outflow-tract-gradient regressed
      to 12 mm Hg. Cardiac catheterization showed an outflow-tract-gradient of 25-36 mm
      Hg and normal coronary arteries. From this observation we conclude that care
      should be taken when prescribing lamotrigine to patients with obstructive
      hypertrophic cardiomyopathy.

PMID- 19581010
TI  - Isolated ventricular noncompaction mimicking arrhythmogenic right ventricular
      cardiomyopathy--a study of nine patients.
AB  - BACKGROUND: Isolated ventricular noncompaction is considered to predominantly
      affect the left ventricle. It is characterized by increased left ventricular wall
      thickness and deep intertrabecular recesses with to-and-fro blood flow that
      remains in continuity with the ventricular flow. Aim of the study was to present
      a group of patients with isolated noncompaction of both ventricles mimicking
      arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Reported group
      consisted of 9 pts initially diagnosed with ARVC (mean age 37.9 y, 7 male), who
      underwent basic clinical evaluation. CMR was performed in 8 pts, cardiac
      catheterization in 2 pts and endomyocardial biopsy in 2 pts. Mean age at
      presentation of first symptoms was 23.5 y (5-44 y). Heart failure symptoms were
      observed in 4 pts, atrial fibrillation in 3 pts, ventricular tachycardia in 2 pts
      (polymorphic--in 2 pts) and syncope in 3 pts. Final diagnosis of noncompaction
      was established according to generally accepted criteria. RESULTS: Morphologic
      and/or functional changes in the right ventricle were seen in 9 pts (100%):
      enlargement and hypertrabeculation of the right ventricle in all pts, global
      hypokinesis in 4 pts, focal wall motion abnormalities and/or bulges typical for
      ARVC in 5 pts. Two pts had significant tricuspid regurgitation. Endomyocardial
      biopsy (2 pts) showed abnormal thick endocardium, interstitial fibrosis,
      myocardial damage and lymphocyte infiltration. CONCLUSIONS: 1) Noncompaction of
      ventricular myocardium should be considered during the evaluation of right
      ventricular cardiomyopathies with excessive trabeculation. 2) In problematic
      cases Task Force criteria for ARVC should be used to improve the accuracy of
      assessment.

PMID- 19581011
TI  - Farm- and flock-level risk factors associated with Highly Pathogenic Avian
      Influenza outbreaks on small holder duck and chicken farms in the Mekong Delta of
      Viet Nam.
AB  - After 11 consecutive months of control, the Mekong Delta in Viet Nam experienced
      a wave of Highly Pathogenic Avian Influenza (HPAI) H5N1 outbreaks on small holder
      poultry farms from December 2006 to January 2007. We conducted a retrospective
      matched case-control study to investigate farm- and flock-level risk factors for
      outbreak occurrence during this period. Twenty-two case farms were selected from
      those where clinical signs consistent with HPAI H5N1 had been present and HPAI
      H5N1 had been confirmed with a positive real-time PCR test from samples obtained
      from affected birds. For every case farm enrolled, two control farms were
      selected matched on time of outbreak occurrence, farm location and species.
      Veterinarians conducted interviews with farmers, to collect information on
      household demographics, farm characteristics, husbandry practices, trading
      practices, poultry health, vaccination and biosecurity. Exact stratified logistic
      regression models were used to assess putative risk factors associated with a
      flock having or not having a HPAI outbreak. Nested analyses were also performed,
      restricted to subsets of farms using scavenging, confinement or supplementary
      feeding practices. Risk of an outbreak of HPAI H5N1 was increased in flocks that
      had received no vaccination (odds ratio (OR)=20.2; 95% confidence interval (CI):
      1.0, +infinity) or only one vaccination (OR=85.2; 95% CI: 6.5, +infinity) of
      flocks compared to two vaccinations, and in flocks on farms that had family and
      friends visiting (OR=8.2; 95% CI: 1.0, +infinity) and geese present (OR=11.5; 95%
      CI: 1.1, +infinity). The subset analysis using only flocks that scavenged showed
      that sharing of scavenging areas with flocks from other farms was associated with
      increased risk of an outbreak (OR=10.9; 95% CI: 1.4, 492.9). We conclude that
      none or only one vaccination, visitors to farms, the presence of geese on farms
      and sharing of scavenging areas with ducks from other farms increase the risk of
      HPAI H5N1 outbreaks in poultry flocks in Viet Nam.

PMID- 19581012
TI  - A rational eating model of binges, diets and obesity.
AB  - This paper addresses the rapid diffusion of obesity and the existence of
      different individual patterns of food consumption between non-dieters and chronic
      dieters. I propose a rational eating model where a forward-looking agent
      optimizes the intertemporal satisfaction from eating, taking into account the
      cost of changing consumption habits and the negative health consequences of
      having a non-optimal body weight. Consistent with the evidence, I show that the
      intertemporal maximization problem leads to a condition of overweightness, and
      that heterogeneity in the individual relevance of habits in consumption can
      determine the observed differences in the individual intertemporal patterns of
      food consumption and body weight. Sufficient conditions for determining when the
      convergence to the steady state implies oscillations or is monotonic are given.
      In the former case, the agent optimally alternates diets and binges until the
      steady state is reached, in the latter a regular intertemporal pattern of food
      consumption is optimal.

PMID- 19581013
TI  - Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival
      in rectal cancer patients with or without preoperative radiotherapy.
AB  - BACKGROUND AND PURPOSE: An exon 2 G4C14-->A4T14 polymorphism in the p73 gene was
      shown to be related to survival in several types of cancers, including colorectal
      cancer. The purpose was to investigate if this polymorphism was related to
      survival in rectal cancer patients with or without preoperative radiotherapy.
      MATERIALS AND METHODS: DNA extracted from tissue of 138 rectal cancer patients
      that received preoperative radiotherapy or had surgery alone was typed for the
      polymorphism by PCR using confronting two-pair primers. RESULTS: Among patients,
      69% had GC/GC genotype, 27% had GC/AT and 4% had AT/AT. In the radiotherapy
      group, patients carrying the AT (GC/AT+AT/AT) allele had stronger expression of
      p53 (p=0.001) and survivin protein (p=0.03) than those carrying the GC/GC
      genotype. Further, among patients receiving preoperative radiotherapy the GC/GC
      genotype tended to be related to better survival (p=0.20). Patients with GC/GC
      genotype, along with negative p53 and weak survivin expression showed better
      survival than the other patients (p=0.03), even after adjusting for TNM stage and
      tumor differentiation (p=0.01, RR, 7.63, 95% CI, 1.50-38.74). In the non
      radiotherapy group, the polymorphism was not related to survival (p=0.74).
      CONCLUSIONS: Results suggest that the p73 G4C14-->A4T14 polymorphism could be one
      factor influencing outcome of preoperative radiotherapy in rectal cancer
      patients.

PMID- 19581014
TI  - Trials and tribulations in charged particle radiotherapy.
AB  - A number of aspects of radiotherapy using protons and ions such as carbon and
      neon are discussed, focusing less on the oft-enumerated advantages or potential
      advantages of these particles as on those aspects which are, or may be,
      problematic. First, for protons and so-called heavy ions separately, the
      potential advantages and disadvantages of the particles, on physical and
      radiobiological grounds, are reviewed and some outstanding problems, both
      technical and scientific, are enumerated. Then, mention is made of the danger
      that financial pressures can lead to suboptimal medical care of patients.
      Finally, the issue of clinical trials, and especially randomized clinical trials,
      is addressed. On the one hand, very few randomized trials have been reported. On
      the other hand, there is a widespread desire to see trials of charged particle
      therapy undertaken. The ethical considerations are briefly reviewed and it is
      concluded that they pose strong limitations on the types of trials which can be
      undertaken. Nevertheless, some clinical trials would certainly be appropriate and
      desirable and a number are suggested, under the categories of retrospective non
      randomized clinical trials, prospective non-randomized clinical trials, and
      prospective-randomized clinical trials.

PMID- 19581015
TI  - The human leukocyte antigen class II gene has different contributions to
      autoimmune type 1 diabetes with or without autoimmune thyroid disease in the
      Japanese population.
AB  - AIM: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AITD).
      The human leukocyte antigen (HLA) has been extensively studied in these diseases.
      We aimed to clarify the contribution of AITD on the susceptibility and resistance
      of the HLA subtype to autoimmune T1D in the Japanese population. METHODS: The
      frequency of the HLA DR-DQ haplotype was compared between 56 autoimmune T1D
      patients with AITD and 71 autoimmune T1D patients without AITD, and control
      subjects. RESULTS: The frequencies of DRB1 0405-DQB1 0401, DRB1 0802-DQB1 0302,
      and DRB1 0901-DQB1 0303 haplotypes were significantly higher in T1D patients with
      AITD than in control subjects. The frequencies of DRB1 0101-DQB1 0501, DRB1 0901
      DQB1 0303, and DRB1 1302-DQB1 0604 haplotypes were significantly higher in T1D
      patients without AITD than in control subjects. The frequencies of DRB1 1101-DQB1
      0301 and DRB1 1501-DQB1 0602 haplotypes were significantly lower in T1D patients
      with or without AITD than in control subjects. CONCLUSIONS: Our results suggest
      that the susceptibility of the HLA subtype to autoimmune T1D differs between T1D
      with AITD and T1D without AITD, whereas there is no difference between the two
      groups with regard to HLA subtypes that confer protection against autoimmune T1D.

PMID- 19581017
TI  - Proteolytic cleavage of chemokines by Trypanosoma cruzi's cruzipain inhibits
      chemokine functions by promoting the generation of antagonists.
AB  - Chagas disease is a chronic inflammatory disease caused by infection with
      Trypanosoma cruzi. Although it had a decline in recent years, it still affects
      millions of people in Latin America. The host immune response against this
      parasite is complex and relies on the development of an efficient T cell-mediated
      response; however, T. cruzi displays a number of evasion mechanisms allowing it
      to remain undetected even for years. One of these is the secretion of anti
      inflammatory molecules such as proteases and the modulation of biological
      functions of chemokines. Our objective was to analyze the effect of a major
      cysteine protease, cruzipain, on a number of critical functions of several CC
      chemokines, both in vitro and in vivo. Initially, using a murine model of T.
      cruzi infection, we demonstrated that CCL-2 and CCL-12 chemokines are highly
      expressed at different stages and correlated with an increase in the expression
      of cruzipain. In addition, we demonstrated that cruzipain is capable of
      differentially cleaving CCL-2 and CCL-12 chemokines, as well as CCL-13. Analysis
      of the proteolysed products identified unique cleavage sites in these chemokines.
      These cruzipain-modified chemokine products were tested in chemotaxis assays
      using monocytic cells. We found that cruzipain treated-CCL-2 maintained its
      biological activity, in contrast to the closely related CCL-12 and CCL-13
      chemokines, which showed little or null agonist activity after treatment.
      Furthermore, based on this analysis, a 14-mer cruzipain-derived chemokine peptide
      (CDCP-1) was chemically synthesized and tested for agonist activity using in
      vitro chemotaxis assays. Interestingly, CDCP-1 showed antagonist activity
      affecting in vitro migration of monocytic cells and calcium flux release. In
      conclusion, our results demonstrate that cruzipain modulates biological functions
      of chemokines through proteolytic cleavage, by generating chemokine-derived
      peptides with antagonist activities. This event could play a role during the
      latest phases of Chagas disease, when the parasite may differentially modulate
      chemokine-mediated inflammatory responses.

PMID- 19581016
TI  - Non-mucinous and mucinous subtypes of adenocarcinoma with bronchioloalveolar
      carcinoma features differ by biomarker expression and in the response to
      gefitinib.
AB  - There is no optimal established therapy for treating advanced or recurrent
      adenocarcinoma with bronchioloalveolar carcinoma features (ADC-BAC), and it
      remains unclear whether chemotherapy achieves therapeutic results comparable to
      those seen in the more common non-small lung carcinoma subtypes. In order to
      improve the decisions made during the treatment of advanced ADC-BAC, we attempted
      to better characterize the mucinous and non-mucinous ADC-BAC subtypes. Fifty
      pathological samples were obtained from 62 patients included in a multicenter
      prospective phase II trial (IFCT0401) conducted to evaluate gefitinib as a first
      line therapy for non-resectable ADC-BAC. These samples were centrally reviewed
      and re-classified as non-mucinous (n=25) or mucinous (n=25) subtypes. We
      demonstrated that demographic data, clinical characteristics and stage at
      presentation (extrathoracic versus lung metastasis, as well as TNM staging) did
      not distinguish between the two subtypes. In contrast, three biological markers
      (PAS staining, TTF-1 expression and EGFR genomic gain combined with mutation
      analysis) enabled us to independently segregate all but 2 of the 50 patients into
      the mucinous and non-mucinous ADC-BAC subtypes. Finally, only mucinous tumors
      appeared to be resistant to epidermal growth factor receptor-tyrosine kinase
      inhibitors (EGFR-TKIs). Additional prospective studies are required to better
      approach therapeutic strategy in mucinous tumors, which are a distinct entity
      from non-mucinous tumors.

PMID- 19581018
TI  - B-1 cell participation in T-cell-mediated alloimmune response.
AB  - B-1 and B cells are important producers of natural antibodies in mice and humans
      and, therefore, are considered as the first line of defense against pathogens.
      Because of that, their role in T-cell-mediated immune responses is commonly
      underrated. However, recent studies have described the participation of B-1 cells
      in immediate and delayed-type hypersensitivity. The present work assessed the
      role of B-1 cells in the rejection of allografts in mice, an immune reaction
      mainly orchestrated by T cells. We have transplanted allogeneic skin and heart to
      wild-type and B-1-cell-deficient mice, and followed rejection kinetics. Skin
      graft-infiltrating cells were analyzed by flow cytometry. We observed a delay in
      rejection kinetics of B-1-cell-deficient mice when compared to wild-type mice.
      Adoptive transfer of B-1 cells into B-1-cell-deficient mice abrogated this delay.
      The longer survival observed in the absence of B-1 cells correlated with less
      CD8+ T cells infiltrating the grafts, as well as with more mast cells.
      Collectively, our results show the participation of B-1 cells in the allograft
      rejection process in mice and collaborate to the understanding of B-1 cell
      biology.

PMID- 19581019
TI  - Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats
      infected with Trypanosoma cruzi.
AB  - Chagas' disease is considered the sixth most important neglected tropical disease
      worldwide. Considerable knowledge has been accumulated concerning the role of
      zinc on cellular immunity. The steroid hormone dehydroepiandrosterone (DHEA) is
      also known to modulate the immune system. The aims of this paper were to
      investigate a possible synchronization of their effects on cytokines and NO
      production and the resistance to Trypanosoma cruzi during the acute phase of
      infection. It was found that zinc, DHEA or zinc and DHEA supplementation enhanced
      the immune response, as evidenced by a significant reduction in parasitemia
      levels. Zinc and DHEA supplementation exerted additive effects on the immune
      response by elevation of macrophage counts, and by increasing concentrations of
      IFN-gamma and NO.

PMID- 19581020
TI  - Soluble macrophage-derived CD163: a homogenous ectodomain protein with a
      dissociable haptoglobin-hemoglobin binding.
AB  - BACKGROUND: The soluble form of the haptoglobin-hemoglobin (Hp-Hb) scavenger
      receptor (sCD163) is a specific plasma/serum marker for macrophage activity.
      Here, we have characterized molecular forms in serum and investigated a role of
      sCD163 as a binder of Hp-Hb complexes. METHODS: The sCD163 species in serum (from
      50 healthy subjects and 29 patients) were measured with domain-specific ELISAs,
      purified from serum (from 6 individuals) by affinity chromatography and
      identified by western blotting and MALDI-TOF/TOF mass spectrometry. Binding to Hp
      Hb complexes was investigated by gel-chromatography, surface plasmon resonance
      (SPR) analyses, and inhibition of Hp-Hb endocytosis in CD163-transfected Chinese
      hamster ovary (CHO) cells. RESULTS: By using C- and N-terminal-specific ELISAs,
      no sCD163 concentration differences in plasma were seen, thus indicating a
      homogenous sCD163 species. Affinity-purified sCD163 from serum migrated as a
      single band of 130kDa, and spanned at least 945 amino acids (94%) of the total
      extra-cellular part of CD163. In solution sCD163 only weakly competed for Hp-Hb
      uptake in CD163-expressing cells, and Hp-Hb saturation of sCD163 in serum was
      only seen with large excess of Hp-Hb complexes. However, upon immobilisation,
      recombinant sCD163 bound Hp-Hb with high affinity. This suggests that Hp-Hb is
      less dissociable when bound to the membrane form of CD163, presumably because of
      the di- or multivalent nature of Hp-Hp complexes in terms of CD163 binding.
      CONCLUSIONS: Serum sCD163 is a homogenous protein covering more than 94% of the
      CD163 ectodomain including the Hp-Hb-binding region. However, CD163 is a poor
      competitor of Hp-Hb uptake, probably because of its soluble nature, where Hp-Hb
      cannot take advantage of receptor cross-linkage.

PMID- 19581021
TI  - Vascular smooth muscle cells promote endothelial cell adhesion via microtubule
      dynamics and activation of paxillin and the extracellular signal-regulated kinase
      (ERK) pathway in a co-culture system.
AB  - Interaction between endothelial cells (ECs) and vascular smooth muscle cells
      (VSMCs) plays an important role in vascular biology. Cell adhesion to the
      extracellular matrix provides critical environmental information necessary for
      cell migration, proliferation, differentiation and survival. In this study, the
      role of VSMCs in EC adhesion was demonstrated by using a co-culture system. It
      was shown that the co-cultured VSMCs significantly increased the number of
      adherent ECs, and induced an increase of total focal adhesion area in ECs. These
      changes were associated with a low microtubule-to-tubulin ratio, and activation
      of extracellular signal-regulated kinase (ERK) and paxillin. Both the EC adhesion
      state and activation of the ERK/paxillin pathway by the co-cultured VSMCs could
      be inhibited by trichostatin A (TSA). As an inhibitor of histone deacetylase, TSA
      acts by modulating microtubule polymerization state. Taken together, these data
      suggest that the co-cultured VSMCs promote EC adhesion by modulating the
      microtubule cytoskeleton polymerization state, which in turn activates the ERK
      pathway and up-regulates phosphorylated paxillin expression to accelerate focal
      adhesion formation.

PMID- 19581022
TI  - Deferoxamine-induced neurite outgrowth and synapse formation in postnatal rat
      dorsal root ganglion (DRG) cell cultures.
AB  - Deferoxamine (DFO) was granted orphan drug status for the treatment of traumatic
      spinal cord injury but its neuroprotective mechanism is not well understood. We
      therefore investigated the mode of action of DFO in serum-starved and/or iron
      stressed cultures of rat dorsal root ganglion (DRG) cells. We probed for redox
      signaling by determining hemeoxygenase-1 activity and by measuring expression of
      intracellular iron metabolism-related proteins under pro-oxidative conditions. We
      also employed DNA microarrays to better understand the genomic response of DRG
      cultures to treatment with DFO thereby enabling the generation of hypotheses.
      Essentially, DFO treatment resulted in outgrowth of neurofilament 200-positive
      neurites and induction of synapse formation as determined by immunoblotting,
      transmission electron microscopy and immunofluorescence confocal microscopy.
      Furthermore, DFO treatment of DRG cell cultures activated neuroprotective and
      antioxidative programs such as matrix metallopeptidase 2 and apolipoprotein D to
      promote neurite regeneration. Indeed, DFO reduced markedly reactive oxygen
      species formation, increased the expression of hemeoxygenase-1 and improved iron
      management through regulation of transferrin receptor and ferritin. We propose
      DFO treatment of DRG cell cultures to completely abolish the oxidative effect of
      ferrous iron (Fe(2+)). Taken collectively, DFO reduced oxidative stress and
      induced synthesis of neuroprotective and antioxidative molecules to foster nerve
      repair and functional recovery. Our findings help to better understand the
      therapeutic benefit of DFO in the treatment of spinal cord injury.

PMID- 19581023
TI  - Biosynthesis of uterotonic diterpenes from Montanoa tomentosa (zoapatle).
AB  - Montanoa tomentosa (zoapatle) is a Central American plant used in Mexico in
      traditional herbal medicine to ease childbirth labor and to cure certain female
      disorders. Recently, crude extracts of M. tomentosa have been reported to have an
      aphrodisiacal effect on male rats. The bioactive molecules are the uterotonic
      diterpenes kaurenoic acid (KA), grandiflorenic acid (GF), and monoginoic acid
      (MO). Roots of M. tomentosa contain all three diterpenes, whereas in leaves only
      kaurenoic and GF are present. However, despite the pharmacological importance of
      these compounds, specific information about their biosynthesis and localization
      in the plant is not available. In this investigation, we followed the metabolic
      transformation of a tritium-labeled diterpene-precursor via geranylgeranyl
      diphosphate into each of the three diterpenes. Inhibitors of gibberellin
      biosynthesis were used to elucidate the sequence of conversion of the
      intermediates. Our results suggest the biosynthetic conversion of KA into GF by a
      putative cytochrome P450-like desaturase. Partial characterization of the enzyme
      revealed that it requires NADPH and O2 but is inhibited by 50 microM
      paclobutrazol, suggesting a cytochrome P450 desaturase like enzyme (EC 1.14.14.
      ). Optimal reaction conditions are 32 degrees C and a pH of 7.6, respectively.
      Apparent kinetics parameters for KA gave a K(m,app) of 36.31 microM, and a V(max,
      app) of 13.6 nmol KA mg(1)protein h(-1). Based on the data presented, a putative
      biosynthetic pathway is proposed for the uterotonic diterpenes of M. tomentosa.

PMID- 19581024
TI  - Quantitative structure-activity relationship analysis of aryl alkanol piperazine
      derivatives with antidepressant activities.
AB  - Quantitative structure-activity relationship analysis for recently synthesized
      aryl alkanol piperazine derivatives was studied for their antidepressant
      activities. The statistically significant 2D-QSAR models (r(2)>0.924, r(
      CV)(2)>0.870, r(-pred)(2)>0.890) were developed using genetic function
      approximation (GFA) when the number of descriptors in equation was set to four,
      indicating the descriptors of Atype_C_6, Dipole-mag, S_sssCH and Jurs-PNSA-3
      mainly influence the 5-hydroxytryptamine (5-HT) reuptake inhibition activity
      while the descriptors of HOMO, PMI-mag, S_sssN and Shadow-XZ may chiefly control
      the noradrenaline (NA) reuptake inhibition activity. The results of the 2D-QSAR
      models were further compared with 3D-QSAR models generated by molecular field
      analysis (MFA), investigating the substitutional requirements for the favorable
      receptor-drug interaction and providing useful information in the
      characterization and differentiation of their binding sites. The results derived
      may be useful in further designing novel antidepressants prior to synthesis.

PMID- 19581025
TI  - Synthesis and antibacterial activity of some new thiazole and thiophene
      derivatives.
AB  - Dibenzobarrelene 1 was reacted with cyanoacetic acid hydrazide and
      thiosemicarbazide to give the corresponding 3-oxo-propiononitrile and thioamide
      derivatives 2 and 16, respectively. The base-catalyzed reaction 3-oxo
      propiononitrile derivative 2 with phenyl isothiocyanate yielded the non-isolable
      intermediate 3. Treatment of 3 with dilute HCl afforded the corresponding
      thiocarbamoyl derivative 4. The intermediate 3, thiocarbamoyl 4 and thioamide
      derivatives 16 were utilized as key intermediates for the synthesis of some new
      thiazole 5, 6a, 6b, 7, 8, 10a, 10b, 12, 14a, 15, 17a, 17b, and 18; and thiophene
      13a-d derivatives, respectively. The newly synthesized compounds were
      characterized by IR, (1)H NMR, (13)C NMR and mass spectral studies.
      Representative compounds of the synthesized product were tested and evaluated as
      antibacterial agent.

PMID- 19581026
TI  - Teaching and learning care--exploring nursing students' clinical practice.
AB  - Care has always been a key element of nursing. This paper presents findings from
      research on the following issue: What opportunities and limitations do nursing
      students encounter when learning nursing care? The study has a qualitative design
      with field methodology and the study of documents. Six nursing students have been
      closely monitored during their clinical studies in hospitals, nursing homes and
      home-based nursing. The study shows that nursing students are likely to possess
      the potential to provide care for sick and unknown people. The motivation for
      their commitment to patients may contain an egoistical orientation and runs
      contrary to former ideals of the nurse's self-sacrificing altruism. Moreover the
      study shows that there is a potential in the clinical field and in the university
      college to reflective considerations on experience of care. While clinical
      practice often has focus on practical problem-solving and procedures, the college
      tends to focus on abstract theory. Both of these promote the privatisation and
      neglect of the students' experience of care. The paper concludes with a call for
      teaching and learning strategies targeting the use of nursing students' personal
      experience of care.

PMID- 19581027
TI  - Education to promote culturally competent nursing care--a content analysis of
      student responses.
AB  - The aim of this study was to describe and analyse the outcome of a 3-year study
      program from a student perspective for the purpose of promoting culturally
      congruent nursing care. Students were asked to complete questionnaires that
      included cases with open-ended questions at the beginning and end of the 3-year
      program. Two nursing situations were described and the students had to imagine
      how they would act in such cases. Ninety-two students completed the two
      questionnaires and the result of a manifest content analysis of their answers is
      presented. Four categories were formulated from the content analysis; an inviting
      attitude, a non-inviting attitude, a knowledge-driven attitude and a non
      knowledge-driven attitude. An inviting attitude meant that the students found
      different strategies for approaching the patient and his/her spouse or parent. A
      non-inviting attitude implied that the students became frustrated with the
      situation and had more difficulty finding solutions that would enhance the
      relationship. A knowledge-driven attitude meant that the students described how
      they found it important to base nursing actions on knowledge of the patient. A
      non-knowledge-driven attitude meant that the students' responses indicated that
      they did not consider knowledge to be the foundation of their nursing actions.
      The study demonstrates marked changes in the students' approaches to culturally
      sensitive issues at the end of the education program.

PMID- 19581028
TI  - Partnering with migrant friendly organizations: a case example from a Canadian
      school of nursing.
AB  - Worldwide immigration to many high-income countries suggests that these
      countries' health care systems must become responsive to a more diverse
      population. Experiences working with newly arrived populations can provide
      healthcare students, professionals, and teachers, with valuable insight into the
      health and social conditions these newcomers face in both source and receiving
      countries. One way to gain this experience may be by developing partnerships
      between schools of nursing in receiving countries and international health
      organizations working in areas that are major migrant source regions for these
      countries. In this paper, we use a case example to describe, the process of
      identifying international, migrant-focused organizations, and the steps involved
      in developing partnerships with these organizations, for the implementation of a
      migrant health component in health professional curricula. After creating a set
      of criteria to evaluate partnership potential, we identified a list of
      international health organizations with whom we thought a partnership might be
      possible. Following application of our criteria, future work is being pursued
      with two organizations. Potential implications of this partnership include
      benefits to all parties involved that may help us move towards increased
      population and public health capacity.

PMID- 19581029
TI  - Novel sampling methods for atmospheric semi-volatile organic compounds (SOCs) in
      a high altitude alpine environment.
AB  - High- and low-volume active air samplers as well as bulk deposition samplers were
      developed to sample atmospheric SOCs under the adverse conditions of a mountain
      environment. Active sampling employed separate filters for different European
      source regions. Filters were switched depending on daily trajectory forecasts,
      whose accuracy was evaluated post hoc. The sampling continued on three alpine
      summits over five periods of four months. The prevailing trajectories varied
      stronger between sampling periods than between stations. The sampling equipment
      (active and bulk deposition) proved dependable for operation in a mountain
      environment, with idle times being mainly due to non-routine manipulations and
      connectivity.

PMID- 19581030
TI  - VOC in an urban and industrial harbor on the French North Sea coast during two
      contrasted meteorological situations.
AB  - Two measurement campaigns of volatile organic compounds (VOC) were carried out in
      the industrial city of Dunkerque, using Radiello passive samplers during winter
      (16-23 January) and summer (6-13 June) 2007. 174 compounds were identified
      belonging to six chemical families. Classifying sampling sites with similar
      chemical profiles by hierarchical ascending classification resulted in 4 groups
      that reflected the influence of the main industrial and urban sources of
      pollution. Also, the BTEX (Benzene, Toluene, Ethylbenzene and Xylenes)
      quantification allowed us to map their levels of concentration. Benzene and
      toluene (BT) showed high concentrations in Northern Dunkerque reflecting the
      influence of two industrial plants. Differences among spatial distributions of
      the BT concentrations over contrasted meteorological conditions were also
      observed. An atypical ratio of T/B in the summer samples led us to investigate
      the BTEX origins shedding light on the contribution of pollutants transported
      across various zones of VOC emissions situated in Europe.

PMID- 19581032
TI  - Cuspal deflection, strain and microleakage of endodontically treated premolar
      teeth restored with direct resin composites.
AB  - OBJECTIVES: To measure cuspal deflection and tooth strain, plus marginal leakage
      and gap formation caused by polymerization shrinkage during direct resin
      composite restoration of root-filled premolars. METHODS: Thirty-two first and
      second maxillary premolars were divided into four groups (n=8). Group 1 had
      standardised mesio-occlusal-distal (MOD) cavities and served as the control
      group. Group 2 had endodontic access and root canal treatment through the
      occlusal floor of the MOD cavity, leaving the axial dentine intact. Group 3 had
      endodontic access and root canal treatment with the mesial and distal axial
      dentine removed. Group 4 had endodontic access and root canal treatment with
      axial dentine removed and a glass ionomer base (GIC). All groups were restored
      incrementally using a low shrink resin composite. Cuspal deflection was measured
      using direct current differential transformers (DCDTs), and buccal and palatal
      strain was measured using strain gauges. Teeth were immersed in 2% methylene blue
      for 24h, sectioned and scored for leakage and gap formation under light and
      scanning electron microscopy. RESULTS: Total cuspal deflection was 4.9+/-1.3
      microm for the MOD cavity (group 1), 7.8+/-3.3 microm for endodontic access with
      intact axial dentine (group 2), 12.2+/-2.6 microm for endodontic access without
      axial dentine (group 3), and 11.1+/-3.8 microm for endodontic access with a GIC
      base (group 4). Maximum buccal strain was 134+/-56, 139+/-61, 251+/-125, and
      183+/-63 mustrain for groups 1-4 respectively, while the maximum palatal strain
      was 256+/-215, 184+/-149, 561+/-123, 264+/-87 mustrain respectively. All groups
      showed marginal leakage; however placement of GIC base significantly improved the
      seal (p=0.007). CONCLUSION: Cusp deflection and strain increased significantly
      when axial dentine was removed as part of the endodontic access. Placement of a
      glass ionomer base significantly reduced tooth strain and marginal leakage.
      Therefore, a conservative endodontic access and placement of a glass ionomer base
      are recommended if endodontically treated teeth undergo direct restoration with
      resin composite.

PMID- 19581033
TI  - Subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest: a
      prospective computed tomography study.
AB  - AIM: Aneurysmal subarachnoid haemorrhage (SAH) is a relatively common cause of
      out-of-hospital cardiac arrest (OHCA). Early identification of SAH-induced OHCA
      with the use of brain computed tomography (CT) scan obtained immediately after
      resuscitation may help emergency physicians make therapeutic decision as quickly
      as they can. METHODS: During the 4-year observation period, brain CT scan was
      obtained prospectively in 142 witnessed non-traumatic OHCA survivors who remained
      haemodynamically stable after resuscitation. Demographics and clinical
      characteristics of SAH-induced OHCA survivors were compared with those with
      "negative" CT finding. RESULTS: Brain CT scan was feasible with an average door
      to-CT time of 40.0 min. SAH was found in 16.2% of the 142 OHCA survivors.
      Compared with 116 survivors who were negative for SAH, SAH-induced OHCA survivors
      were significantly more likely to be female, to have experienced a sudden
      headache, and trended to have achieved return of spontaneous circulation (ROSC)
      prior to arrival in the emergency department less frequently. Ventricular
      fibrillation (VF) was significantly less likely to be seen in SAH-induced than
      SAH-negative OHCA (OR, 0.06; 95% CI, 0.01-0.46). Similarly, Cardiac Trop-T assay
      was significantly less likely to be positive in SAH-induced OHCA (OR, 0.08; 95%
      CI, 0.01-0.61). CONCLUSION: Aneurysmal SAH causes OHCA more frequently than had
      been believed. Immediate brain CT scan may particularly be useful in excluding
      SAH-induced OHCA from thrombolytic trial enrollment, for whom the use of
      thrombolytics is contraindicated. The low VF incidence suggests that VF by itself
      may not be a common cause of SAH-induced OHCA.

PMID- 19581031
TI  - Unusual sleep experiences, dissociation, and schizotypy: Evidence for a common
      domain.
AB  - This paper reviews studies that have examined associations between unusual sleep
      experiences (including nightmares, vivid dreaming, narcolepsy symptoms, and
      complex nighttime behaviors) and dissociation and schizotypy. Using correlational
      studies and structural analyses, evidence is provided that unusual sleep
      experiences, dissociation, and schizotypy belong to a common domain. It is
      demonstrated that unusual sleep experiences show specificity to dissociation and
      schizotypy compared to other daytime symptoms (e.g., anxiety, depression,
      substance use) and other sleep disturbances (e.g., insomnia, lassitude/fatigue).
      The paper also outlines the methodological limitations of the existing evidence
      and makes suggestions for future research. Finally, three models for the overlap
      of daytime and nighttime symptoms are reviewed, including biological
      abnormalities, trauma, and personality traits. Although further research is
      needed, it is suggested that daytime and nighttime symptoms result from problems
      with sleep-wake state boundaries, which may be precipitated by stress or trauma.
      In addition, association between daytime and nighttime symptoms can be attributed
      to the higher order personality trait of Oddity.

PMID- 19581034
TI  - Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a
      porcine ventricular fibrillation model.
AB  - OBJECTIVES: The aim of the study was to investigate the effect on calcium cycling
      protein and electrical restitution of beta(1)-adrenergic receptor antagonist
      esmolol administered during cardiopulmonary resuscitation in the porcine
      ventricular fibrillation model. METHODS: Ventricular fibrillation untreated for
      four minutes was induced by dynamic steady state pacing protocol in 40 healthy
      male pigs, in which local unipolar electrograms were recorded using one 10
      electrode catheter that was sutured to the left ventricular epicardium. During
      CPR, animals were randomized into two groups to receive saline as placebo or
      esmolol after two standard doses of epinephrine. At post-resuscitation 2-h, six
      pigs were randomly selected from each group and the second VF induction was
      performed. Local activation-recovery intervals (ARI) restitutions and the VF
      inducibility between control group and esmolol group were compared. Western
      blotting was performed to determine expression of Ca(2+)/calmodulin-dependent
      protein kinase IIdelta(CaMKIIdelta) and cardiac ryanodine receptor (RyR2)
      protein, and their phosphorylation status. RESULTS: Injection of esmolol combined
      with epinephrine during CPR significantly decreased recurrent rate of ventricular
      fibrillation during 2-h post-resuscitation, meanwhile it has no adverse affect on
      the restore of spontaneous circulation. Esmolol significantly flattened ARI
      restitution slope, lessened regional difference of ARI restitution, decreased the
      VF inducibility, and alleviated CaMKIIdelta hyper-activation and RyR2 hyper
      phosphorylation. CONCLUSIONS: Esmolol given during CPR has significant effects on
      modulating electrical restitution property and intracellular calcium handling,
      which contributes the most important reasons why beta(1)-blockade significantly
      reduced the onset and maintenance of VF.

PMID- 19581035
TI  - Treatment of asystole and PEA.
AB  - Recent reports consistently point to a substantial decline in the incidence of
      ventricular fibrillation (VF) as the initial rhythm observed by Emergency Medical
      Service (EMS) responders and a complementary increase in pulseless electrical
      activity (PEA) and asystole. Historically, efforts at improving survival have
      focused primarily on patients found in VF. Consequently, the approach for other
      patients has included frequent pauses in cardiopulmonary resuscitation (CPR) to
      check for VF followed by shock when VF is observed. However, the "yield" of
      survivors comes largely from the non-shocked patients. Therefore, it is critical
      that we start evaluating treatments specifically for the PEA and asystole groups.

PMID- 19581036
TI  - Rescuer fatigue during actual in-hospital cardiopulmonary resuscitation with
      audiovisual feedback: a prospective multicenter study.
AB  - BACKGROUND: Rescuer fatigue during cardiopulmonary resuscitation (CPR) is a
      likely contributor to variable CPR quality during clinical resuscitation efforts,
      yet investigations into fatigue and CPR quality degradation have only been
      performed in simulated environments, with widely conflicting results. OBJECTIVE:
      We sought to characterize CPR quality decay during actual in-hospital cardiac
      arrest, with regard to both chest compression (CC) rate and depth during the
      delivery of CCs by individual rescuers over time. METHODS: Using CPR recording
      technology to objectively quantify CCs and provide audiovisual feedback, we
      prospectively collected CPR performance data from arrest events in two hospitals.
      We identified continuous CPR "blocks" from individual rescuers, assessing CC rate
      and depth over time. RESULTS: 135 blocks of continuous CPR were identified from
      42 cardiac arrests at the two institutions. Median duration of continuous CPR
      blocks was 112s (IQR 101-122). CC rate did not change significantly over single
      rescuer performance, with an initial mean rate of 105+/-11/min, and a mean rate
      after 3 min of 106+/-9/min (p=NS). However, CC depth decayed significantly
      between 90s and 2 min, falling from a mean of 48.3+/-9.6mm to 46.0+/-9.0mm
      (p=0.0006) and to 43.7+/-7.4mm by 3 min (p=0.002). CONCLUSIONS: During actual in
      hospital CPR with audiovisual feedback, CC depth decay became evident after 90s
      of CPR, but CC rate did not change. These data provide clinical evidence for
      rescuer fatigue during actual resuscitations and support current guideline
      recommendations to rotate rescuers during CC delivery.

PMID- 19581037
TI  - Tako Tsubo cardiomyopathy in a patient with multiple trauma.
AB  - Tako Tsubo cardiomyopathy has been described in a variety of stress situations,
      including several critical illness settings. We report the first case of this
      syndrome in a patient with multiple trauma. Tako Tsubo is an unusual cause of
      circulatory failure in such patients, to be distinguished from myocardial
      contusion and myocardial infarction. Prolonged ST segment elevation on EKG, minor
      troponin release, and transient left ventricular apical ballooning on
      transthoracic echocardiography are among the features to be recognized. Full
      recovery occurs spontaneously within several weeks.

PMID- 19581038
TI  - Is a 4 days transoesophageal training course sufficient to diagnose shock related
      pathologies?
AB  - INTRODUCTION: Echocardiography is a useful tool in patients suffering from shock
      of unknown origin to evaluate cardiac function and volume status in order to
      decide on further treatment. The aim of the study was to evaluate how well
      participants could identify function, preload and regional wall motion
      abnormalities after attending a 4-day transoesophageal echocardiography (TOE)
      seminar. METHODS: In this prospective educational trial, participants of six TOE
      seminars from 2005 to 2006 were evaluated. On the basis of seven
      echocardiographic studies, evaluations by participants concerning cardiac
      function, preload and regional wall motion were analyzed. Moreover, specific
      causes of undifferentiated hypotension were to be judged in three cases by the
      participants. RESULTS: A total of 115 participants of the TOE seminars from 2005
      to 2006 were evaluated. Correct sectional plane was recognized by more than 76%
      of the participants. Left ventricular function, preload, and regional wall
      abnormalities were assessed correctly by the participants in 98%, 96%, and 84%,
      respectively. Moreover, more than 70% of the participants recognized the correct
      cause of hemodynamic instability. CONCLUSION: The results of the investigation
      show that participants of a 4-day TOE seminar can interpret left ventricular
      function, preload and regional wall motion abnormalities correctly at a very high
      rate. TOE seminars seem to be effective in teaching basic theoretical knowledge
      of TOE.

PMID- 19581039
TI  - Analysis of limited resuscitations in patients suffering in-hospital cardiac
      arrest.
AB  - BACKGROUND: Although clinicians are expected to help patients make decisions
      about end-of-life care, there is insufficient data to help guide patient
      preferences. The objective of this study was to determine the frequency of
      patients who undergo 'limited code' and compare survival to discharge with those
      who undergo maximum resuscitative efforts ('full code'). METHODS: We performed a
      retrospective analysis of all adult in-hospital cardiac arrests (IHCA) at a
      tertiary care teaching hospital from January 1999 to December 2003 to compare
      survival in patients with limited code to survival in patients with a full code.
      We collected data on demographic and clinical variables known to influence
      survival in IHCA. Logistic regression was used to assess the association of code
      status with subsequent survival through the code and to hospital discharge after
      adjusting for potential confounding factors. RESULTS: Of the 309 patients having
      IHCA, there were 17 (5.5%) patients with limited code status and 292 (94.5%) with
      full code status. Among full code patients, 171 (58.6%) survived the code
      compared to five patients (29.4%) who had a limited code (p=0.023). After
      adjusting for demographic variables and pre-arrest co-morbidities, patients with
      full code status compared to limited code status had an odds ratio for return of
      spontaneous circulation of 3.69 (95% CI: 1.13-14.34). CONCLUSIONS: Patients who
      opt for limited code have a significantly lower probability of survival compared
      to patients who choose full code. Patients who choose limited code should be
      informed of the likely negative outcome as compared to full resuscitation.

PMID- 19581040
TI  - Investigation of the possibility of using ischemia-modified albumin as a novel
      and early prognostic marker in cardiac arrest patients after cardiopulmonary
      resuscitation.
AB  - BACKGROUND: Early and accurate prediction of survival to hospital discharge
      following resuscitation after cardiac arrest (CA) is a major challenge. Our aim
      was to investigate the levels of ischemia-modified albumin (IMA) and
      malondialdehyde (MDA) in CA patients and whether IMA levels are valuable early
      marker of post-cardiopulmonary resuscitation prognosis in CA patients. METHODS:
      We enrolled 52 in- or out-of-hospital CA patients, with 47 healthy volunteers as
      the control group (CG). Blood samples were taken for IMA and MDA measurement at
      the beginning or within 5 min of commencement of CPR. The patients were
      classified according to the Glasgow Outcome Score (GOS) into a poor outcome group
      (POG) and a good outcome group (GOG). RESULTS: Mean IMA levels were higher in POG
      (0.25+/-0.07 ABSU) than in GOG (0.19+/-0.07 ABSU, p=0.002) and also than CG
      (0.16+/-0.04 ABSU, p=0.0001). The IMA levels were not significantly higher in GOG
      than in CG (p=0.32). The mean MDA levels in POG (0.77+/-0.27 nmol/ml) were
      comparable to the levels in GOG (0.75+/-0.18 nmol/ml, p>0.05), but were
      significantly higher than in CG (0.60+/-0.15 nmol/ml, p=0.001). MDA levels were
      not significantly higher in GOG than in CG (p=0.06). The optimum cut-off point
      for IMA maximizing sensitivity and specificity was 0.235 ABSU, with sensitivity
      of 65.8% and specificity of 78.6%. The corresponding +PV and -PV were 85.3% and
      45.8%, respectively. CONCLUSION: In conclusion, though the result may not be
      applied clinically in every patient, the ischemia-modified albumin may be a
      valuable prognostic marker in cardiac arrest patients following CPR.

PMID- 19581041
TI  - Images in resuscitation: ECG misinterpretion underneath high-voltage power lines.

PMID- 19581042
TI  - Fatal complication secondary to mechanical chest compression device.

PMID- 19581043
TI  - Tuition of emergency medical dispatchers in the recognition of agonal respiration
      increases the use of telephone assisted CPR.
AB  - OBJECTIVES: Bystanders cardiopulmonary resuscitation (CPR) increases survival in
      out-of-hospital cardiac arrest (OHCA). Emergency medical dispatchers (EMDs) can
      provide even totally inexperienced bystanders with instructions by telephone on
      how to resuscitate victims (T-CPR) until the emergency medical services (EMS)
      arrive. Agonal respiration makes it difficult for EMDs to identify cardiac
      arrests (CAs) which will prevent or delay initiation of T-CPR. The aim of this
      investigation was to study if tuition of EMDs can improve their ability to
      identify agonal respiration in OHCA to allow for more frequent offers of T-CPR.
      METHODS: An observational study was made in 2004 and subsequently, a repeat study
      was made in 2006. All OHCA (n=315 in 2004, n=255 in 2006) in the Stockholm region
      reported to the Swedish Cardiac Arrest Register were included and all
      corresponding EMS reports were reviewed. Emergency calls were recorded during the
      event. Witnessed cases of OHCA (n=76 in both 2004 and 2006) were analyzed using a
      structured data collection tool. RESULTS: The frequency of offered T-CPR to all
      bystanders of OHCA in 2004 was 47%. After special tuition on agonal respiration
      in OHCA it rose to 68% in 2006 (p=0.01). An even more marked rise was observed in
      OHCA cases with agonal respiration. In 2004 T-CPR was offered in 23% of these
      situations whereas the corresponding figures in 2006 had risen to 56% (p=0.006).
      CONCLUSIONS: Teaching EMDs to understand and recognize bystander descriptions of
      agonal respiration in patients with OHCA has resulted in a significant increase
      in offers of T-CPR in these situations.

PMID- 19581044
TI  - A comparison of customized and population-based birth-weight standards: the
      influence of gestational age.
AB  - OBJECTIVES: We examined how customized birth-weight standards compare to
      population birth-weight references at term (> or =37 weeks), nearly term (34-36
      weeks), moderately preterm (32-33 weeks) and for the very preterm births (28-31
      weeks), with respect to perinatal mortality. STUDY DESIGN: Data from the national
      Swedish Medical Births Register for the years 1992-2001, consisting of a total of
      783,303 singletons born at or after 28 completed gestational weeks. Infants were
      classified as small for gestational age (SGA, <10th centile) according to a
      conventional population based birth-weight reference and a customized standard.
      Risk ratios (RR) for still birth and neonatal death were compared between
      standards by prematurity of the birth. Diagnostic performance measures of
      specificity, sensitivity and positive and negative predictive values were also
      evaluated. RESULTS: More than half, 59% (209), of the 355 infants still-born
      between 28 and 31 weeks gestation were classified as SGA by the customized
      standard, but only 23% (80), were so classified as SGA by the population
      reference. However, only 14% (95%CI 13-16) of the 1461 very preterm infants
      classified as SGA by the customized standard were still-born, compared to 23%
      (95%CI 19-28) of the 348 infants classified as SGA by the population reference.
      Therefore, the relative risk of still birth for those classified as SGA by the
      customized standard is lower, 2.02 (95%CI: 1.65, 2.46), than for the population
      reference 2.64 (95%CI: 2.11, 3.30). Similar results were observed for the risk of
      neonatal death. For term weeks, customized standards showed stronger
      relationships than population references (RR: 4.30 (95%CI 3.82, 4.84) vs. 4.00
      (95%CI 3.55, 4.51) for still births). CONCLUSIONS: Customized standards
      categorize a higher absolute number of preterm infants who are still-born as SGA.
      However, infants classified as SGA by population references are at higher risk of
      perinatal mortality than infants classified as SGA by customized standards.

PMID- 19581047
TI  - Surface modification of glass beads with glutaraldehyde: characterization and
      their adsorption property for metal ions.
AB  - In this study, a new material that adsorbs the metal ions was prepared by
      modification of the glass beads surfaces with glutaraldehyde. First, the glass
      beads were etched with 4M NaOH solution. Then, they were reacted with 3
      aminopropyl-triethoxysilane (APTES). Finally, silanized glass beads were treated
      with 25% of glutaraldehyde solution. The characterization studies by using
      Fourier Transform Infrared Spectroscopy (FT-IR), Thermal Gravimetric Analysis
      (TGA), elemental analysis and Scanning Electron Microscopy (SEM) indicated that
      modification of the glass bead surfaces was successfully performed. The
      adsorption studies exhibited that the modified glass beads could be efficiently
      used for the removal of the metal cations and anion (chromate ion) from aqueous
      solutions via chelation and ion-exchange mechanisms. For both Pb(II) and Cr(VI),
      selected as model ions, the adsorption equilibrium was achieved in 60 min and
      adsorption of both ions followed the second-order kinetic model. It was found
      that the sorption data was better represented by the Freundlich isotherm in
      comparison to the Langmuir and Redlich-Peterson isotherm models. The maximum
      adsorption capacities for Pb(II) and Cr(VI) were 9.947 and 11.571 mg/g,
      respectively. The regeneration studies also showed that modified glass beads
      could be re-used for the adsorption of Pb(II) and Cr(VI) from aqueous solutions
      over three cycles.

PMID- 19581046
TI  - Vascular endothelial growth factor (VEGF) enhances gastric carcinoma invasiveness
      via integrin alpha(v)beta6.
AB  - Integrins play an important role in tumor metastasis induced by vascular
      endothelial growth factor (VEGF). However, in the case of gastric cancer, the
      precise role of VEGF in regulating integrin alphavbeta6 is unclear. In this
      study, we found that most of the alphavbeta6 integrin-positive gastric cancer
      tissues were also VEGF-positive. Furthermore, when gastric carcinoma cells were
      exposed to VEGF, expression of alphavbeta6 integrin was up-regulated and the
      extracellular signal-related kinase (ERK) pathway was activated. When integrin
      alphavbeta6 was blocked either with beta6 siRNA or anti-alphavbeta6 antibody, the
      migration of tumor cells normally induced by VEGF, as well as the activation of
      ERK, were markedly inhibited. Blocking the ERK signaling pathway significantly
      inhibited cell mobility. Taken together, the data suggest that VEGF is critical
      to the invasive process in human gastric cancer and that this occurs via up
      regulation of integrin alphavbeta6 expression and activation of ERK.

PMID- 19581048
TI  - Synthesis of Mg(II) doped goethite and its cation sorption behaviour.
AB  - Modified goethite samples were prepared with Mg(II) content varying in the range
      of 0-1.36%. A typical TEM of Mg(II) doped sample showed needle shaped goethite
      particles having 10-30 nm width and 100-400 nm length. Sorption studies of
      cations namely Pb(II), Cu(II), Cd(II), Zn(II) and Fe(III) were conducted onto the
      Mg(II) doped modified goethite surface. Goethite doping with 0.18 M Mg (GMg(2))
      showed better sorption capacity for Pb(II), Cu(II) and Cd(II). Therefore, the
      effect of contact time, solution pH, sorbate and sorbent concentrations on the
      sorption of various metal ions was studied on this sample in batch experiments.
      The time data fitted to pseudo-second-order kinetics for all the metal ions.
      Sorption on GMg(2) sample for the metal ions increased with the increase in pH
      from 2 to 4. The isothermic data showed good fit to both Langmuir and Freundlich
      isotherms except for Cd(II) which followed only the later model. The sorption
      capacities with respect to Pb(II), Cd(II), Zn(II), Cu(II) and Fe(III) were found
      to be 87.7, 153.25, 86.25, 33.4 and 72.5mg/g respectively. The results of
      sorption studies on GMg(2) from binary and ternary solutions have also been
      presented. The XRD patterns of metal ion loaded GMg(2) samples confirmed that
      metal ion adsorption resulted in shifting of d-values/altering of relative
      intensity (RI) of major planes of goethite.

PMID- 19581049
TI  - Rice hull/MnFe2O4 composite: preparation, characterization and its rapid
      microwave-assisted COD removal for organic wastewater.
AB  - Adsorbent/ferrite composites can adsorb and degrade organics in the organic
      wastewater treatment. In this study, a rice hull/MnFe(2)O(4) composite (RHM) was
      prepared via calcination under nitrogen atmosphere and was used to treat organic
      wastewater with the assistance of microwave radiation. Rice hull was pyrolysed to
      a porous substrate that consisted of silica and activated carbon under high
      temperature. Monodisperse spinel MnFe(2)O(4) nanoparticles whose mean diameter is
      around 59 nm are distributed on the substrate. With the assistance of microwave
      radiation, RHM was motivated to a hotspot of adsorption and catalysis which could
      remove more than 70% COD of wastewater within 6 min. The maximum COD removal was
      73.5% when the concentration of RHM was 15 mg mL(-1) and the irradiation time of
      microwave radiation was 6 min. Although the BET surface area and iodine value of
      RHM are half of rice hull ash (RHA), the COD removal of RHM is 7-20% higher than
      that of RHA. It is attributed to the presence of MnFe(2)O(4), which enhances the
      catalytic activity of RHM. RHM can be regenerated via water washing. However, the
      surface area and the maximum COD removal of RHM decrease for each regeneration
      cycle. With the advantages of low cost and rapid processing, this novel rice
      hull/MnFe(2)O(4) composite could gain promising application in wastewater
      treating-agent.

PMID- 19581050
TI  - Aqueous organic dye discoloration induced by contact glow discharge electrolysis.
AB  - In this study, effects of applied voltage, types of electrolytes, initial
      substrate concentration, radical scavengers and iron salts on the aqueous polar
      brilliant B (PBB) discoloration induced by contact glow discharge electrolysis
      (CGDE) were examined. Experimental results showed that the PBB discoloration
      proceeded faster in chloride solution than in phosphate or sulfate solutions.
      Increasing the applied voltage from 450V to 550V did not enhance the
      discoloration when the applied current was kept constant. Addition of a small
      amount of hydroxyl scavengers (methanol) to the solution decreased the
      discoloration, whereas addition of a large amount of methanol increased the
      discoloration. During the treatment, TOC of the solution smoothly decreased
      whereas COD of the solution gradually increased due to the production of H(2)O(2)
      in the liquid phase. Iron salts enhanced the discoloration significantly due to
      the additional Fenton reaction. Higher initial PBB concentration resulted in
      lower color removal efficiency, indicating that the PBB discoloration by CGDE did
      not observe the first-order reaction kinetics in inert electrolytic solutions.

PMID- 19581051
TI  - Trends in prescribed opioid therapy for non-cancer pain for individuals with
      prior substance use disorders.
AB  - Long-term opioid therapy for non-cancer pain has increased. Caution is advised in
      prescribing for persons with substance use disorders, but little is known about
      actual health plan practices. This paper reports trends and characteristics of
      long-term opioid use in persons with non-cancer pain and a substance abuse
      history. Using health plan data (1997-2005), the study compared age-sex
      standardized rates of incident, incident long-term and prevalent long-term
      prescription opioid use, and medication use profiles in those with and without
      substance use disorder histories. The CONsortium to Study Opioid Risks and Trends
      study included adult enrollees of two health plans, Kaiser Permanente of Northern
      California (KPNC) and Group Health Cooperative (GH) of Seattle, Washington. At
      KPNC (1999-2005), prevalence of long-term use increased from 11.6% to 17.0% for
      those with substance use disorder histories and from 2.6% to 3.9% for those
      without substance use disorder histories. Respective GH rates (1997-2005),
      increased from 7.6% to 18.6% and from 2.7% to 4.2%. Among persons with an opioid
      disorder, KPNC rates increased from 44.1% to 51.1%, and GH rates increased from
      15.7% to 52.4%. Long-term opioid users with a prior substance abuse diagnosis
      received higher dosage levels, were more likely to use Schedule II and long
      acting opioids, and were more often frequent users of sedative-hypnotic
      medications in addition to their opioid use. Since these patients are viewed as
      higher risk, the increased use of long-term opioid therapy suggests the
      importance of improved understanding of the benefits and risks of opioid therapy
      among persons with a history of substance abuse, and the need for more careful
      screening for substance abuse history than is the usual practice.

PMID- 19581052
TI  - Immunoproteomic analysis of the second-generation merozoite proteins of Eimeria
      tenella.
AB  - Whole proteins of the second-generation merozoite of Eimeria tenella were
      analyzed by two-dimensional gel electrophoresis (2-DE) and western blot using the
      chicken sera infected artificially with E. tenella. Approximately 640 spots were
      detected on proteome map of the second-generation merozoite stained by Coomassie
      brilliant blue G-250 and 85 spots were recognized on western blot map as
      antigens. Forty four spots of the antigens were identified by matrix-assisted
      laser desorption ionization time-of-flight MS (MALDI-TOF-MS) and MALDI-TOF-TOF
      MS. Twenty six proteins of E. tenella and three homologous proteins to other
      apicomplexan parasites or protozoan were identified using 'Mascot' server. These
      proteins included lactate dehydrogenase, enolase, 14-3-3 protein, microneme
      proteins, tubulin beta chain, SERPIN1 protein precursor, large subunit ribosomal
      protein L23 and surface antigens of E. tenella, heat shock protein (HSP70) of
      Eimeria acervulina, protein phosphatase type 1 of Toxoplasma gondii and
      hypothetical protein GSPATT00020155001 of Paramecium tetraurelia. The rest
      proteins were searched against the E. tenella protein sequence database using
      'Mascot in-house' (version 2.1) search engine in automated mode and 11 unknown
      proteins were identified. After the amino acid sequence of the unknown proteins
      were searched using BLAST against non-redundant sequence databases (NCBI),
      surface antigen 12 of E. tenella and six homologous proteins to other apicomplexa
      parasites were found. They were membrane skeleton protein IMC2A, mitochondrial F1
      ATP synthase beta subunit precursor, 3-oxoacyl-acyl-carrier-protein synthase and
      catalase of T. gondii, Vps26 of Plasmodium falciparum 3D7, and hypothetical
      protein TRIADDRAFT_60424 of Trichoplax adhaerens. No homologues of 8 spots of the
      44 analyzed proteins were found. These proteins enriched the data of immunogenic
      proteins of the second-generation merozoite of E. tenella.

PMID- 19581053
TI  - The possible effect of altitude on regional variation in suicide rates.
AB  - In the United States, suicide rates consistently vary among geographic regions;
      the western states have significantly higher suicide rates than the eastern
      states. The reason for this variation is unknown but may be due to regional
      elevation differences. States' suicide rates (1990-1994), when adjusted for
      potentially confounding demographic variables, are positively correlated with
      their peak and capital elevations. These findings indicate that decreased oxygen
      saturation at high altitude may exacerbate the bioenergetic dysfunction
      associated with affective illnesses. Should such a link exist, therapies
      traditionally used to treat the metabolic disturbances associated with altitude
      sickness may have a role in treating those at risk for suicide.

PMID- 19581054
TI  - Do sauna therapy and exercise act by raising the availability of
      tetrahydrobiopterin?
AB  - Sauna therapy has been used to treat a number of different diseases known or
      thought to have a tetrahydrobiopterin (BH4) deficiency. It has been interpreted
      to act in multiple chemical sensitivity by increasing chemical detoxification and
      excretion but there is no evidence that this is its main mode of action. Sauna
      therapy may act to increase BH4 availability via two distinct pathways. Increased
      blood flow in heated surface tissues leads to increased vascular shear stress,
      inducing increased activity of GTP cyclohydrolase I (GTPCH-I) in those vascular
      tissues which will lead to increasing BH4 synthesis. A second mechanism involves
      the heat shock protein Hsp90, which is induced by even modest heating of
      mammalian tissues. Sauna heating of these surface tissues may act via Hsp90,
      which interacts with the GTPCH-I complex and is reported to produce increased
      GTPCH-I activity by lowering its degradation. The increased consequent
      availability of BH4 may lead to lowered nitric oxide synthase uncoupling, such as
      has been reported for the eNOS enzyme. Increased BH4 synthesis in surface tissues
      of the body will produce increased circulating BH4 which will feed BH4 to other
      body tissues that may have been BH4 deficient. Similar mechanisms may act in
      vigorous exercise due to the increased blood shear stresses and possibly also
      heating of the exercising tissues and heart. There is a large and rapidly
      increasing number of diseases that are associated with BH4 depletion and these
      may be candidates for sauna therapy. Such diseases as hypertension, vascular
      endothelial dysfunction, multiple chemical sensitivity and heart failure are
      thought to be helped by sauna therapy and chronic fatigue syndrome and
      fibromyalgia may also be helped and there are others that may be good candidates
      for sauna therapy.

PMID- 19581055
TI  - Potential of vitamin E as an antioxidant adjunct in Wilson's disease.
AB  - Wilson's disease is a rare genetic illness of copper metabolism, which leads to
      copper-overload in mitochondria and organ damage, especially to the liver.
      Oxidative stress is central to the pathogenesis and a case is briefly made for
      rigorous trials of vitamin E as an antioxidant adjunct based on earlier corollary
      studies of its levels in the blood and liver of Wilson's disease patients and its
      effects in animal models of the illness.

PMID- 19581056
TI  - Patterns of regional recurrence after definitive radiotherapy for cervical
      cancer.
AB  - PURPOSE: To determine the patterns of regional recurrence in patients treated
      with definitive radiotherapy (RT) for cervical cancer. METHODS AND MATERIALS: The
      records of 198 patients treated with definitive RT for cervical cancer between
      1980 and 2000 who experienced a regional recurrence without a central or distal
      vaginal recurrence were reviewed. All patients received a combination of external
      beam RT and intracavitary brachytherapy. In the 180 patients with a documented
      location of regional recurrence, the relationship between the recurrence and the
      radiation fields was determined. RESULTS: The median time to regional recurrence
      was 13 months (range, 2-85 months). Of the 180 patients who had an evaluable
      regional recurrence, 119 (66%) had a component of marginal failure; 71 patients
      recurred above-the-field, 2 patients occurred in the inguinal nodes, and 2
      patients recurred above-the-field and in the inguinal nodes. In addition, 105
      patients (58%) had a component of in-field failure; 59 patients recurred in-field
      only, 39 patients recurred in-field and above-the-field, 2 patients recurred in
      field, above-the-field, and in the inguinal nodes, and 5 patients recurred in
      field and in the inguinal nodes. The median survival after regional recurrence
      was 8 months (range, 0-194 months). CONCLUSIONS: Most regional recurrences after
      definitive RT for cervical cancer include a component of marginal failure,
      usually immediately superior to the radiation field. These recurrences suggest a
      deficiency in target volume. Recurrences also occur in-field, suggesting a
      deficiency in dose. Developments in pretreatment staging, field delineation, dose
      escalation, and posttreatment surveillance may help to improve outcome in these
      patients.

PMID- 19581057
TI  - Development and validation of the Alcoholics Anonymous Intention Measure (AAIM).
AB  - BACKGROUND: Drop-out from 12-step groups is notoriously high, yet the field lacks
      strong models and scales for addressing this problem. We aim to determine whether
      the theory of planned behavior (TPB) can be applied to 12-step involvement, and
      to develop and validate a scale of 12-step readiness based on that theory: the
      Alcoholics Anonymous Intention Measure (AAIM). METHOD: Data were from a
      longitudinal trial of a manual-guided 12-step facilitation intervention called
      Making AA Easier (MAAEZ) involving two treatment programs in California (N=508).
      Participants completed surveys at baseline, 7 weeks, 6 months, and 12 months.
      Surveys included the preliminary AAIM, a 12-step involvement measure, other
      readiness measures, and substance use outcomes. RESULTS: The final, 17-item AAIM
      measured Attitude (5-item alpha's=.75-.83), Subjective Norm (4-item alpha's=.56
      .81), Perceived Control (5-item alpha's=.78-.85), and Intention (3-item
      alpha's=.80-.95) regarding attendance at 12-step groups. Components were
      correlated with each other and other readiness measures as expected, supporting
      the AAIM's validity. Scale components predicted 31% of the variance in Intention
      to attend 12-step groups at 6 months and 41% of the variance in 12-step
      involvement at 12 months. Social factors were among the strongest predictors of
      12-step involvement. Results did not support the expectancy-value formulation of
      the TPB, as unweighted (vs. weighted) belief items performed optimally.
      CONCLUSIONS: Results generally support the TPB as a model of 12-step involvement
      and suggest specific targets for 12-step facilitation interventions within
      attitude, norm, and control components. Findings also support the AAIM as a tool
      for identifying drop-out risks and tailoring individual interventions.

PMID- 19581058
TI  - Field trial evaluating changes in prevalence and patterns of antimicrobial
      resistance among Escherichia coli and Enterococcus spp. isolated from growing
      broilers medicated with enrofloxacin, apramycin and amoxicillin.
AB  - The present study investigates, under field conditions, the influence of
      antimicrobial administration on prevalence and patterns of antimicrobial
      resistance among Escherichia coli and Enterococcus spp. isolated from growing
      broilers. For this purpose, a group of 16,000 commercial broiler chickens was
      treated with enrofloxacin from day 1 to day 3, gentamicin from day 19 to day 21,
      and ampicillin from day 26 to day 28. A control group of 16,000 broilers was
      placed in the same controlled environment poultry house. Fecal (from both groups)
      and feed samples were collected at regular intervals. Few E. coli isolates were
      obtained from either farm environment or poultry feed samples, while enterococci
      were found to be ubiquitous among these samples. The frequency of resistance
      against most antimicrobials tested was significantly higher (P<0.05) in E. coli
      isolated from broilers receiving intermittent antimicrobial pressure than that
      from non-medicated broilers, whereas in enterococci these differences were only
      observed among structurally related antimicrobial drugs and over a short period
      of time. By the time the broilers reached market age (33 days), several multi
      resistant E. coli and enterococci were detected in the feces of the medicated
      group. Results suggest that antimicrobial resistance in E. coli was mainly
      medication-dependent, whereas among enterococci, changes observed over time were
      apparently influenced by factors apart from antimicrobial exposure, namely the
      resistance organisms previously present in farm environment and those present in
      feedstuffs.

PMID- 19581059
TI  - New recognition of Enterovirus infections in bottlenose dolphins (Tursiops
      truncatus).
AB  - An enterovirus was cultured from an erosive tongue lesion of a bottlenose dolphin
      (Tursiops truncatus). The morphology of virions on negative staining electron
      microscopy was consistent with those of enteroviruses. Analysis of 2613 bp of the
      polyprotein gene identified the isolate as a novel enterovirus strain,
      tentatively named bottlenose dolphin enterovirus (BDEV), that nests within the
      species Bovine enterovirus. Serologic evidence of exposure to enteroviruses was
      common in both free-ranging and managed collection dolphins. Managed collection
      dolphins were more likely to have high antibody levels, although the highest
      levels were reported in free-ranging populations. Associations between
      enterovirus antibody levels, and age, sex, complete blood counts, and clinical
      serum biochemistries were explored. Dolphins with higher antibody levels were
      more likely to be hyperproteinemic and hyperglobulinemic.

PMID- 19581060
TI  - Computational radiology in skeletal radiography.
AB  - Recent years have brought rapid developments in computational image analysis in
      musculo-skeletal radiology. Meanwhile the algorithms have reached a maturity that
      makes initial clinical use feasible. Applications range from joint space
      measurement to erosion quantification, and from fracture detection to the
      assessment of alignment angles. Current results of computational image analysis
      in radiography are very promising, but some fundamental issues remain to be
      clarified, among which the definition of the optimal trade off between
      automatization and operator-dependency, the integration of these tools into
      clinical work flow and last not least the proof of incremental clinical benefit
      of these methods.

PMID- 19581061
TI  - 18F-FDG PET/CT in the evaluation of POEMS syndrome.
AB  - In POEMS syndrome the identification and biopsy of an osteosclerotic lesion or a
      lymph node typical of Castleman's disease (CD) is essential to establish the
      diagnosis and plan appropriate treatment. We report four patients in whom the
      localisation and identification of diagnostic bone lesions or lymphadenopathies
      were guided by fluorodeoxyglucose positron emission tomography integrated with
      computerised tomography (FDG PET/CT). FDG PET/CT identified bone lesions not
      detected with other techniques in one patient, and revealed hypermetabolic
      characteristics in bone lesions or adenopathies in the others, thus guiding the
      diagnostic biopsy in those with hypermetabolism. In conclusion, FDG PET/CT may be
      useful in detecting and selecting bone lesions and lymph nodes for biopsy in
      patients with suspected POEMS syndrome.

PMID- 19581062
TI  - Characteristic findings in images of extra-pancreatic lesions associated with
      autoimmune pancreatitis.
AB  - PURPOSE: Autoimmune pancreatitis is a unique form of chronic pancreatitis
      characterized by a variety of extra-pancreatic involvements which are frequently
      misdiagnosed as lesions of corresponding organs. The purpose of this study was to
      clarify the diagnostic imaging features of extra-pancreatic lesions associated
      with autoimmune pancreatitis. MATERIALS AND METHODS: We retrospectively analyzed
      diagnostic images of 90 patients with autoimmune pancreatitis who underwent
      computer-assisted tomography, magnetic resonance imaging, and/or gallium-67
      scintigraphy before steroid therapy was initiated. RESULTS: AIP was frequently
      (92.2%) accompanied by a variety of extra-pancreatic lesions, including swelling
      of lachrymal and salivary gland lesions (47.5%), lung hilar lymphadenopathy
      (78.3%), a variety of lung lesions (51.2%), wall thickening of bile ducts
      (77.8%), peri-pancreatic or para-aortic lymphadenopathy (56.0%), retroperitoneal
      fibrosis (19.8%), a variety of renal lesions (14.4%), and mass lesions of the
      ligamentum teres (2.2%). Characteristic findings in CT and MRI included
      lymphadenopathies of the hilar, peri-pancreatic, and para-aortic regions; wall
      thickening of the bile duct; and soft tissue masses in the kidney, ureters,
      aorta, paravertebral region, ligamentum teres, and orbit. CONCLUSIONS:
      Recognition of the diagnostic features in the images of various involved organs
      will assist in the diagnosis of autoimmune pancreatitis and in differential
      diagnoses between autoimmune pancreatitis-associated extra-pancreatic lesions and
      lesions due to other pathologies.

PMID- 19581063
TI  - Accelerated time-resolved three-dimensional MR velocity mapping of blood flow
      patterns in the aorta using SENSE and k-t BLAST.
AB  - PURPOSE: To assess the feasibility and potential limitations of the acceleration
      techniques SENSE and k-t BLAST for time-resolved three-dimensional (3D) velocity
      mapping of aortic blood flow. Furthermore, to quantify differences in peak
      velocity versus heart phase curves. MATERIALS AND METHODS: Time-resolved 3D blood
      flow patterns were investigated in eleven volunteers and two patients suffering
      from aortic diseases with accelerated PC-MR sequences either in combination with
      SENSE (R=2) or k-t BLAST (6-fold). Both sequences showed similar data acquisition
      times and hence acceleration efficiency. Flow-field streamlines were calculated
      and visualized using the GTFlow software tool in order to reconstruct 3D aortic
      blood flow patterns. Differences between the peak velocities from single-slice PC
      MRI experiments using SENSE 2 and k-t BLAST 6 were calculated for the whole
      cardiac cycle and averaged for all volunteers. RESULTS: Reconstruction of 3D flow
      patterns in volunteers revealed attenuations in blood flow dynamics for k-t BLAST
      6 compared to SENSE 2 in terms of 3D streamlines showing fewer and less distinct
      vortices and reduction in peak velocity, which is caused by temporal blurring.
      Solely by time-resolved 3D MR velocity mapping in combination with SENSE detected
      pathologic blood flow patterns in patients with aortic diseases. For volunteers,
      we found a broadening and flattering of the peak velocity versus heart phase
      diagram between the two acceleration techniques, which is an evidence for the
      temporal blurring of the k-t BLAST approach. CONCLUSION: We demonstrated the
      feasibility of SENSE and detected potential limitations of k-t BLAST when used
      for time-resolved 3D velocity mapping. The effects of higher k-t BLAST
      acceleration factors have to be considered for application in 3D velocity
      mapping.

PMID- 19581064
TI  - Paediatrician awareness of radiation dose and inherent risks in chest imaging
      studies--a questionnaire study.
AB  - OBJECTIVE: To assess paediatricians' knowledge regarding radiation exposure of
      chest imaging. MATERIALS AND METHODS: German paediatricians were surveyed using a
      questionnaire. Participants were asked to estimate effective dose (ED) of
      radiographs (CR) and computed tomography (CT). Further questions included dose
      saving of paediatric CT-protocols, ALARA principle, and awareness of the link
      between radiation and cancer development. Length and type of occupation and
      amount of ordered procedures were evaluated. RESULTS: 137 paediatricians
      participated with 59% and 39% correctly estimating ED of an adult (0.01-0.1mSv)
      and newborn CR (0.01-0.1mSv), respectively. ED of an adult chest CT (1-10mSv) was
      underestimated by 28%, whereas ED of cardiac CT (10-100mSv) was underestimated by
      54%. 35% of participants correctly estimated ED of a chest CT in an infant (10
      100mSv) which was underestimated by 56%. Neither length nor type of occupation
      showed significant impact on dose estimations. 14% of paediatricians stated that
      MRI causes radiation, whereas 4% correctly estimated the potential of paediatric
      CT-protocols. 15% were familiar with the ALARA principle and 26% were aware of a
      publication concerning radiation and malignancy. CONCLUSION: Paediatricians
      demonstrated an increased level of awareness compared to previous surveys.
      However, estimation of ED of CT remained difficult. Increased information
      transfer and education seem pressing in the light of increasing radiological
      examinations.

PMID- 19581065
TI  - Development of enzyme-linked immunosorbent assay for 8-iso-prostaglandin F2alpha,
      a biomarker of oxidative stress in vivo, and its application to the
      quantification in aged rats.
AB  - 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha) is one of the isoprostanes that are
      mainly generated nonenzymatically in vivo from arachidonic acid through free
      radical-induced lipid peroxidation. To assess oxidative stress in vivo, we
      developed a quantitative enzyme-linked immunosorbent assay (ELISA) for 8-iso
      PGF2alpha. A sensitive calibration curve allowed the quantification of the
      amounts from 0.23 pg to 98.4 pg with 4.7 pg of 50% displacement in one assay. The
      ELISA method was applied to the measurement of the plasma levels of 8-iso
      PGF2alpha in young rats (4-8 weeks of age) and aged rats (106-123 weeks). The
      average level of esterified form in the plasma from aged rats was 30.6-fold
      higher than that in the plasma from young rats, reflecting the enhanced status of
      oxidative stress in aged animals. In addition, the aged rats exhibited higher
      levels of this F2-isoprostane esterified to lipids from liver and kidney,
      suggesting local oxidative injury in specific organs. These results indicate the
      utility and accuracy of our ELISA for 8-iso-PGF2alpha as a biomarker in vivo to
      assess systemic oxidative stress in animals or humans as well as oxidative injury
      at local sites.

PMID- 19581066
TI  - Production of a reactive metabolite of troglitazone by electrochemical oxidation
      performed in nonaqueous medium.
AB  - In order to confirm the existence of reactive metabolites by LC-MS/MS analysis,
      they should be modified into stable compounds, because some reactive metabolites
      generated by biotransformation induce drug toxicity; however, they are unstable,
      with very short lives, and cannot be detected in their intact forms. To overcome
      these problems, electrochemical oxidation of troglitazone was performed in
      nonaqueous medium, since such reactive compounds are stable in the absence of
      water. Troglitazone, an antidiabetic agent, was withdrawn from the market because
      of serious hepatotoxicity in some patients. It has been considered that one or
      more reactive metabolites are involved in hepatotoxicity, although the mechanism
      of the adverse reaction is unclear. Using our method of electrochemical oxidation
      in nonaqueous medium, we obtained a product of troglitazone derivative that may
      be a clue to clarify the mechanism of toxicity. The product in the reaction
      mixture was separated by HPLC without chemical modification and detected using UV
      and ESI-MS. The mass spectrum of its molecular ion showed that it was an o
      quinone methide derivative of troglitazone and identified as a reactive
      metabolite generated by liver microsome oxidation of the drug. The product was
      stable over 24 h at room temperature in anhydrous acetonitrile, but it reacted
      with N-(tert-butoxycarbonyl)-L-cystein methylester to produce an adduct that
      could be identified by its m/z value. Thus, the method of electrochemical
      oxidation in nonaqueous medium is considered to be useful to prepare and predict
      reactive metabolites of drugs that are unstable in aqueous medium or in vivo.

PMID- 19581067
TI  - Structural identification and characterization of potential degradants of
      zotarolimus on zotarolimus-coated drug-eluting stents.
AB  - Identification and characterization of unknown zotarolimus impurities on
      zotarolimus-coated drug-eluting stents is an important aspect of product
      development since the presence of impurities can have a significant impact on
      quality and safety of the drug product. Four zotarolimus degradation products
      have been characterized by LC/UV/PDA, LC/MS, LC/MS/MS and NMR techniques in this
      work. Zotarolimus drug substance and zotarolimus-coated stents were subjected to
      degradation under heat, humidity, acid or base conditions. The HPLC separation
      was achieved on a Zorbax Eclipse XDB-C8 column using gradient elution and UV
      detection at 278 nm. All four impurities generated through the degradation were
      initially analyzed by LC/MS and/or LC/MS/MS for structural information. Then the
      isolation of these degradants was carried out by semi-preparative HPLC method
      followed by freeze-drying of the collected fractions. Finally the degradants were
      studied by 1H and 13C NMR spectrometry. Based on LC/MS, 1H NMR and 13C NMR data,
      the structures of these impurities were proposed and characterized as zotarolimus
      ring-opened isomer (1), zotarolimus hydrolysis product, 16-O-desmethyl ring
      opened isomer (2) and zotarolimus lower fragment (3). Degradants 1, 2 and 3 have
      been observed on degraded zotarolimus-coated stent products.

PMID- 19581068
TI  - Magnetic particle-based chemiluminescence enzyme immunoassay for free thyroxine
      in human serum.
AB  - A magnetic particles-based chemiluminescence enzyme immunoassay with high
      sensitivity, specificity, rapidity, and reproducibility was developed for the
      determination of free thyroxine in human serum. A competitive assay has been
      proposed with horseradish peroxidase labeled thyroxine analog. The immunomagnetic
      particles coated with anti-fluorescein isothiocyanate antibody was used as
      dispersed solid phase and separation means for the immunoassay. Experimental
      conditions, such as temperature, the volume of magnetic particles and substrate,
      incubation time, dilution ratio and other relevant variables upon the immunoassay
      have been examined and optimized. The proposed method exhibited high performance
      which the linear range was 1.59-122 pmol L(-1) and the detection limit was 0.25
      pmol L(-1). A coefficient of variance of less than 15% was obtained for both
      intra-assay and inter-assay precision. The present method has been successfully
      applied to the analysis of free thyroxine in human serum. The diagnostic
      accordance rate of the method for normal serum, hyperthyroidism and
      hypothyroidism are satisfactory. Good correlations were obtained between the
      results by the proposed method and the commercial radioimmunoassay kit. The
      present method exhibits good potential in the fabrication of FT4 diagnostic kits
      which could be used in the clinical analysis and facilitated the development of
      automated operation systems in the clinical practice.

PMID- 19581069
TI  - Adaptive Conjoint Analysis as individual preference assessment tool: feasibility
      through the internet and reliability of preferences.
AB  - OBJECTIVE: Patient values are not routinely assessed in clinical practice.
      Adaptive Conjoint Analysis (ACA) is increasingly applied in studies assessing
      treatment preferences, and could provide a means to routinely assess individual
      patients' treatment preferences. METHODS: An ACA-questionnaire was administered
      three times (7-10 days apart) to 98 long-term rectal cancer survivors either on a
      portable computer or through internet, to assess whether (a) responses differ
      according to administration mode, (b) relative importances of rectal cancer
      treatment outcomes (survival, local control, incontinence, sexual problems)
      consolidate over time, (c) ACA-outcomes are sufficiently reliable (ICC) for use
      in individual decision-making. We also evaluated patients' acceptance of ACA.
      RESULTS: Mode did not affect ACA-completion or evaluation. Importance scores did
      not consolidate over time. ICCs were poor for sexual problems and fair for the
      other outcomes, and were at least equal or higher from first to second retest.
      Most participants valued completing the ACA-questionnaire and learning their
      results. CONCLUSION: Values did not show consolidation over time. ACA-derived
      preferences should not determine which treatment patients should choose. PRACTICE
      IMPLICATIONS: Findings extend ACA-validation studies to the health care setting
      and suggest that ACA-questionnaires might be appreciated as adjuncts to treatment
      decision-making in newly diagnosed patients.

PMID- 19581070
TI  - An audit of nephroureterectomy for upper tract urothelial carcinoma.
AB  - BACKGROUND: The boundary of nephroureterctomy has been revisited and lymph node
      dissection has been recommended recently. We investigated the role of synchronous
      ipsilateral adrenalectomy in treating patients with upper tract urothelial
      carcinoma. METHODS: 110 patients with clinically localized upper tract urothelial
      carcinoma treated by nephroureterectomy and bladder cuff resection were
      retrospectively evaluated. 70 patients underwent nephroureterectomy without
      concomitant ipsilateral adrenalectomy, whereas nephroureterectomy and ipsilateral
      adrenalectomy was performed in other 40 patients. Cancer specific, metastasis and
      local recurrence free survival during a follow-up of median 46 months were
      analyzed. RESULTS: No patient had adrenal metastasis among the 40
      adrenalectomized patients. A total of 4 patients developed local recurrences;
      including 1 of the 70 adrenalectomy-sparing and 3 of the 40 adrenalectomized
      patients (p = 0.102, chi-square test). Five patients with adrenalectomy and four
      without adrenalectomy had distant metastases (p = 0.212, chi-square test). The
      five-year local recurrence free survival (p = 0.09, log-rank test), metastasis
      free survival (p = 0.292, log-rank test), and cancer-specific survival (p =
      0.117, log-rank test) did not have significant difference between both groups.
      CONCLUSIONS: This is the only study in recent 2 decades to evaluate the necessity
      of synchronous adrenalectomy in treating localized upper tract urothelial
      carcinoma. Adrenal-sparing nephroureterectomy seems justified for clinically
      localized upper tract urothelial carcinoma.

PMID- 19581071
TI  - Assisting people with multiple disabilities and minimal motor behavior to improve
      computer pointing efficiency through a mouse wheel.
AB  - This study evaluated whether two people with multiple disabilities and minimal
      motor behavior would be able to improve their pointing performance using finger
      poke ability with a mouse wheel through a Dynamic Pointing Assistive Program
      (DPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces
      standard mouse driver, changes a mouse wheel into a thumb/finger poke detector,
      and intercepts mouse action). Initially, both participants had their baseline
      sessions. Then intervention started with the first participant. When his
      performance was consolidated, new baseline and intervention occurred with the
      second participant. Finally, both participants were exposed to maintenance phase,
      in which their pointing performance improved significantly. Both participants
      improved their pointing efficiency with the use of DPAP and remained highly
      successful through maintenance phase. Implications of the findings are discussed.

PMID- 19581072
TI  - Evaluation of duration of epilepsy prior to temporal lobe epilepsy surgery during
      the past two decades.
AB  - We examined whether duration of epilepsy prior to temporal lobe resection has
      decreased over the years as a result of increasing body of evidence in the
      literature showing the benefits of anterior temporal resection. We stratified the
      213 patients, who had their first temporal lobe resection at our center between
      1996 and 2007 into three groups in order to detect any trends in duration of
      epilepsy: group A (surgery between 1996 and 1999); group B (surgery between 2000
      and 2003); group C (surgery between 2004 and 2007). No difference in mean
      duration of epilepsy was detected between the three groups (p=0.54). The mean
      duration in epilepsy prior to temporal lobe resection has persisted at greater
      than 20 years during the past two decades.

PMID- 19581073
TI  - Chemoradiation in gynaecological cancer.
AB  - In the radical treatment of cervical cancer there is now overwhelming evidence to
      support cisplatin-based chemoradiation with radical radiotherapy for locally
      advanced disease. This is, however, at the expense of increased acute toxicity,
      in particular grade 3 and 4 haematological toxicity and acute gastrointestinal
      toxicity. In the setting of the developing world it is important to note that the
      impact of chemoradiation over radiotherapy alone diminishes with advancing stage
      and the overall benefit where the patients have predominantly stage III and IV
      disease is small and particularly where supportive therapy is limited may be
      outweighed by increased toxicity. Greater gains may be achieved by attention to
      delivering high-quality conventional radiotherapy, including brachytherapy.
      Endometrial cancer is a rare tumour compared with cervical cancer in the
      developing world. The evidence for chemotherapy having a role in the routine
      management of high-risk disease defined by high-grade histology or stage IC and
      above is tenuous and cannot be recommended for healthcare systems where resources
      are limited. There is clearly an increasing trend in developed countries to offer
      patients with advanced inoperable vulval carcinoma chemoradiation, but without
      any primary evidence of increased efficacy. It is associated with increased
      toxicity and as with cervical cancer an emphasis on high-quality, high-dose,
      carefully planned megavoltage radiotherapy alone may make far greater gains in
      this population.

PMID- 19581074
TI  - Short-term increase of serum troponin I and serum heart-type fatty acid-binding
      protein (H-FABP) in dogs following administration of formoterol.
AB  - In this paper, changes in serum levels of the cardiac biomarkers troponin I and
      the heart-type fatty acid-binding protein (H-FABP) following administration of a
      long-acting beta(2)-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs
      were measured. We measured troponin I in dogs in a 4-week repeated-dose study
      with inhalative administration of formoterol (13microg/kgd) and a
      glucocorticoid/formoterol combination (143/16microg/kgd). The medians of troponin
      I increased within 3 days in both groups, far beyond the cut-off level
      (0.1microg/L), but returned to baseline levels on study day 9. The increase was
      more pronounced in the formoterol-only group (3.29microg/L) compared to the
      glucocorticoid/formoterol combination group (1.32microg/L). In a second study, we
      measured serum troponin I as well as serum H-FABP levels in several samples over
      7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol
      combination (120/12mug/kgd). The median of the troponin I concentration increased
      above the cut-off level within 2h and that of H-FABP within 4h. The medians of
      both parameters were temporarily above the cut-off levels even on study day 7.
      Both studies were conducted according to national animal welfare guidelines. To
      our knowledge, this is the first report that shows a corresponding increase of
      troponin I and H-FABP in dogs treated with formoterol. Both parameters are more
      sensitive in detecting a drug-induced cardiac injury compared to total LDH, total
      CK as well as CK MB activity. However, it is recommended to take at least three
      blood samples per day to assess a temporary increase of troponin I.

PMID- 19581075
TI  - Regression of cervical intraepithelial neoplasia by zerumbone in female Balb/c
      mice prenatally exposed to diethylstilboestrol: involvement of mitochondria
      regulated apoptosis.
AB  - BACKGROUND: Cervical cancer is the second most common cause of cancer death in
      women. We have demonstrated previously that zerumbone (ZER) has an anti-cancer
      effect towards human cervical cancer cells (HeLa). METHODS: Anti-cancer
      properties of ZER were investigated using female Balb/c mice exposed prenatally
      to diethylstilboestrol. Female offspring have been treated with ZER (4, 8 and 16
      mg/kg), normal saline and cisplatin (10mg/kg; positive control). The anti-cancer
      properties of ZER were evaluated using histopathology, TdT-mediated dUTP nick end
      labeling (TUNEL) Assay and immunohistochemical staining of Bcl-2-associated X
      protein (Bax), a key protein in mitochondrial pathway of apoptosis. In addition,
      laser capture microdissection microscopy isolated RNA was amplified using reverse
      transcriptase polymerase chain reaction (RT-PCR) based on the specific primer of
      B-cell lymphoma 2 (Bcl-2). RESULTS: Treatment with ZER resulted (P<0.05, chi(2)
      statistics) in the regression of cervical intraepithelial neoplasia (CIN)
      resembling cisplatin effect (10mg/kg). TUNEL micrographs showed the absence of
      apoptosis in cancerous tissues treated with normal saline compared to ZER and
      cisplatin where abundant apoptotic cells were noticed. A post hoc analysis showed
      a significant (P<0.01) difference in mean percentage of apoptosis between normal
      saline treatment (0%), ZER (15.7%) and cisplatin (21.7%). Immunohistochemical
      staining of Bax protein revealed that ZER modulates the expression of this
      apoptosis marker. Administration of ZER has also modulated the expression of Bcl
      2 gene. CONCLUSION: These findings showed that ZER induces apoptosis efficiently
      in cervical tissues from female Balb/c mice treated prenatally with
      diethylstilboestrol. This suggested that ZER, a plant-derived compound, could be
      introduced as a new chemo-preventive agent for CIN in future.

PMID- 19581076
TI  - Toxico-pathological changes induced by cypermethrin in broiler chicks: their
      attenuation with Vitamin E and selenium.
AB  - Ninety 1-day old broiler chicks of mixed gender (as hatched) procured from a
      local hatchery were randomly divided into five equal groups. All the treatments
      were given through crop tubing. Groups 1-4 received cypermethrin (CY) (600mgkg(
      1)b. wt.) daily for 30 days. In addition to CY (group 1), groups 2-4 received Vit
      E (150mgkg(-1)b. wt.), Se (0.25mgkg(-1)b. wt.), and Vit E (150mgkg(-1)b. wt.)+Se
      (0.25mgkg(-1)b. wt.), respectively. Group 5 served as control andreceived normal
      saline (2mlkg(-1)b. wt.) for 30 days. Randomly selected six broiler chicks from
      each group were slaughtered at experimental days 10, 20 and 30 for the collection
      of serum/plasma and morbid tissues. Absolute organ weights were recorded. Total
      plasma proteins, fibrinogen and creatinine were significantly (P<0.05) increased
      while alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and urea decreased
      significantly (P<0.05) in CY-treated group when compared with the control group.
      Kidneys were swollen grossly in treated broiler chicks. In liver, necrosis of
      hepatocytes, cytoplasmic vacuolation, bile duct hyperplasia and mononuclear
      cellular infiltration were observed. In kidneys, necrosis of tubular epithelial
      cells, cytoplasmic vacuolation, cellular infiltration and atrophy of glomeruli
      were observed. Sub-arachnoid space was much dilated in CY-treated broiler chicks.
      It can be concluded that CY induces biochemical and histopathological alterations
      in broilers chicks; however, these toxic effects can be ameliorated by Vit E or
      Se. Combination of Vit E and Se was more effective in ameliorating toxic effects
      of cypermethrin in broilers chicks.

PMID- 19581077
TI  - Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated
      with carbon tetrachloride.
AB  - The possible modulatory effect of methanolic extract of Vernonia amygdalina
      (MEVA), a plant widely consumed in the tropics and used locally in the treatment
      of fever, jaundice, stomach disorders and diabetes on the toxicity of CCl(4), was
      investigated in male rats. Oral administration of CCl(4) at a dose of 1.2g/kg
      body weight 3 times a week for 3 weeks significantly induced marked hepatic
      injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and
      gamma-GT. Methanolic extract of V. amygdalina administered 5 times a week for 2
      weeks before CCl(4) treatment at 250 and 500 mg/kg doses of the extract
      ameliorated the increase in the activities of these enzymes. Likewise the
      methanolic extract of V. amygdalina reduced the CCl(4)-induced increase in the
      concentrations of cholesterol, triglyceride and phospholipid by 37.8%, 30.6% and
      8.5%, respectively, and a reduction in the cholesterol/phospholipids ratio. These
      parameters were however increased at 750 mg/kg extract pretreatment. CCl(4)
      induced lipid peroxidation was likewise attenuated by 57.2% at 500 mg/kg dose of
      the methanolic extract of V. amygdalina. Similarly, administration of the extract
      increased the activities of the antioxidant enzymes: superoxide dismutase,
      glutathione S-transferase and reduced glutathione concentration significantly at
      500 mg/kg (P<0.05) and catalase activity at 500-1000 mg/kg doses. These results
      suggest that methanolic extract of V. amygdalina leaves posseses protective
      effect against CCl(4)-induced hepatotoxicity by the antioxidant mechanism of
      action.

PMID- 19581078
TI  - Determination of heavy metals and halogens in plastics from electric and
      electronic waste.
AB  - The presence of hazardous substances and preparations in small waste electrical
      and electronic equipment (sWEEE) found in the residual household waste stream of
      the city of Dresden, Germany has been investigated. The content of sWEEE plastics
      in heavy metals and halogens is determined using handheld X-ray fluorescence
      analysis (HXRF), elemental analysis by means of atomic absorption spectrometry
      (AAS) and ion exchange chromatography (IEC). Mean value of results for heavy
      metals in samples (n=51) by AAS are 17.4 mg/kg for Pb, 5.7 mg/kg for Cd, 8.4
      mg/kg for Cr. The mass fraction of an additive as shown by HXRF (n=161) can vary
      over a wide range. Precise deductions as regards sWEEE plastics content in
      hazardous substances and preparations cannot be made. Additional research would
      be expedient regarding the influence of hazardous substances to recycling
      processes, in particular regarding the contamination of clean fractions in the
      exit streams of a WEEE treatment plant. Suitable standards for calibrating HXRF
      for use on EEE plastics or complex electr(on)ic components do not exist and
      should be developed.

PMID- 19581080
TI  - Membrane protein crystallization from lipidic phases.
AB  - Membrane protein structural biology is enjoying a steady acceleration in the rate
      of success. Nevertheless, numerous membrane protein targets are resistant to the
      traditional approach of directly crystallizing detergent solubilized and purified
      protein and the 'niche market' of lipidic phase crystallization is emerging as a
      powerful complement. These approaches, including lipidic cubic phase, lipidic
      sponge phase, and bicelle crystallization methods, all immerse purified membrane
      protein within a lipid rich matrix before crystallization. This environment is
      hypothesized to contribute to the protein's long-term structural stability and
      thereby favor crystallization. Spectacular recent successes include the high
      resolution structures of the beta(2)-adrenergic G-protein-coupled receptor, the
      A(2A) adenosine G-protein-coupled receptor, and the mitochondrial voltage
      dependent anion channel. In combination with technical innovations aiming to
      popularize these methods, lipidic phase crystallization approaches can be
      expected to deliver an increasing scientific impact as the field develops.

PMID- 19581079
TI  - Presynaptic plasticity: targeted control of inhibitory networks.
AB  - GABAergic inhibitory interneurons are embedded in almost all central neuronal
      networks, where they act to influence cell excitability, spike timing, synchrony,
      and oscillatory activity, that is, almost every physiologically relevant process
      in the mammalian central nervous system. Consequently, presynaptic plasticity of
      the synaptic input onto, or the outputs from, a single inhibitory interneuron can
      have major ramifications for the activity of the often thousands of downstream
      target neurons. Here we discuss several recently described forms of presynaptic
      long-term potentiation (LTP) and long-term depression (LTD) occurring at synapses
      either made onto inhibitory interneurons, or at inhibitory synapses onto
      downstream targets in a number of central structures. As we will illustrate, the
      induction mechanisms underlying these disparate examples of presynaptic
      plasticity share few common features, however, their expression mechanisms
      converge on the presynaptic release machinery. We hypothesize that these varied
      forms of presynaptic plasticity can operate in a manner fundamentally distinct
      from most postsynaptic 'point to point' forms of plasticity, to achieve powerful
      modification of the integration and output of large-scale networks.

PMID- 19581081
TI  - Removal of benzene and toluene in polyurethane biofilter immobilized with
      Rhodococcus sp. EH831 under transient loading.
AB  - The performance of a polyurethane (PU) biofilter inoculated with Rhodococcus sp.
      EH831 was evaluated under different transient loading conditions, such as
      shutdown, intermittent and fluctuating loading. A mixture of benzene and toluene
      vapors was employed as model pollutants. When the biofilter was restarted after a
      2 week-shutdown, during which neither clean air nor water was supplied, the
      benzene and toluene removal capacities were rapidly restored after a re
      adaptation period of only 1 day. A comparison of the removal capacity under
      continuous and intermittent loading revealed that constant and periodic loading
      (8 h on/16 h off per day) and a 2 day-shutdown did not significantly influence
      the biofilter performance, although the removals of benzene and toluene were
      relatively unstable and lower under intermittent loading during the initial week.
      The result of quantitative real-time PCR showed that Rhodococcus sp. EH831 could
      be maintained during transient loading periods (10(10)-10(11) CFU/g-dry PU)
      irrespective of the different operating conditions.

PMID- 19581082
TI  - Optimisation of the solvent extraction of phenolic antioxidants from fruits of
      Euterpe oleracea using Response Surface Methodology.
AB  - Fruits of Euterpe oleracea (FEO) are currently known as elements that present a
      very high antioxidant activity (AAO), as measured by the Oxygen Radical
      Absorbance Capacity. They are particularly rich in total phenolics (TP) and total
      anthocyanins (TA). Response Surface Methodology was used to optimise the solvent
      extraction of phenolic antioxidants from FEO, using a second-order polynomial
      equation to describe the experimental data for TP, TA, and AAO. In order to
      determine the best solid-to-liquid ratio and time of extraction, some preliminary
      studies were conducted. A rotatable central composite design with three variables
      (ethanol proportion, hydrochloric acid concentration and temperature) was then
      used. The results showed a good fit to the proposed model (R(2)>0.89). TP and TA,
      as well as TA and AAO, showed significant correlations (P<0.05). The optimised
      conditions that maximized the yields of phenolic compounds (TP and TA) and AAO
      from FEO were: ethanol proportion between 70% and 80%, hydrochloric acid
      concentration between 0.065 and 0.074 mol/L and a temperature of 58 degrees C.

PMID- 19581083
TI  - Phytoaccumulation of zinc by the aquatic plant, Lemna gibba L.
AB  - The uptake of zinc (Zn) by the duckweed Lemna gibba L., native to the north-east
      region of Algeria, was investigated in quarter Coic solutions enriched with 6.0,
      10.0, 14.0 and 18.0 mg l(-1) of Zn supplied as zinc sulphate (ZnSO(4)). Zinc
      concentrations were measured in the water daily and in duckweed biomass at the
      end of the experiments. These results showed that under experimental conditions
      (pH=6.0+/-0.1, T=21+/-1 degrees C, photoperiod=12 h/j), L. gibba was able to
      accumulate in its biomass 4.23; 15.62; 23.88 and 25.81 mg g(-1) DM, respectively
      for the four initial concentrations selected. At these concentrations, the metal
      removed percentages were 61-71%. The mass balance performed on the system showed
      that about 49-68% of Zn (depending on the initial concentration in water) was
      removed by precipitation as zinc phosphate. The results showed that this aquatic
      plant can be successfully used for Zn removal.

PMID- 19581084
TI  - Production of polyhydroxyalkanoates (PHAs) from waste materials and by-products
      by submerged and solid-state fermentation.
AB  - Polyhydroxyalkanoates are biodegradable polymers produced by prokaryotic
      organisms from renewable resources. The production of PHAs by submerged
      fermentation processes has been intensively studied over the last 30 years. In
      recent years, alternative strategies have been proposed, such as the use of solid
      state fermentation or the production of PHAs in transgenic plants. This paper
      gives an overview of submerged and solid-state fermentation processes used to
      produce PHAs from waste materials and by-products. The use of these low-cost raw
      materials has the potential to reduce PHA production costs, because the raw
      material costs contribute a significant part of production costs in traditional
      PHA production processes.

PMID- 19581085
TI  - Enhanced enzymatic hydrolysis and structural features of corn stover by FeCl3
      pretreatment.
AB  - Corn stover was pretreated with FeCl(3) to remove almost all of the hemicellulose
      present and then hydrolyzed with cellulase and beta-glucosidase to produce
      glucose. Enzymatic hydrolysis of corn stover that had been pretreated with
      FeCl(3) at 160 degrees C for 20 min resulted in an optimum yield of 98.0%. This
      yield was significantly higher than that of untreated corn stover (22.8%).
      FeCl(3) pretreatment apparently damaged the surface of corn stover and
      significantly increased the enzymatic digestibility, as evidenced by SEM and XRD
      analysis data. FTIR analysis indicated that FeCl(3) pretreatment could disrupt
      almost all the ether linkages and some ester linkages between lignin and
      carbohydrates but had no effect on delignification. The FeCl(3) pretreatment
      technique, as a novel pretreatment method, enhances enzymatic hydrolysis of
      lignocellulosic biomass by destructing chemical composition and altering
      structural features.

PMID- 19581086
TI  - The identification and optimisation of novel and selective diamide neuropeptide Y
      Y2 receptor antagonists.
AB  - A novel small molecule NPY Y2 antagonist (3) identified from high throughput
      screening is described. A subsequent SAR study and optimisation programme based
      around this molecule is also described, leading to the identification of potent
      and soluble pyridyl analogue 36.

PMID- 19581087
TI  - Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from
      Streptomyces platensis.
AB  - Natural products continue to serve as one of the best sources for discovery of
      antibacterial agents as exemplified by the recent discoveries of platensimycin
      and platencin. Chemical modifications as well as discovery of congeners are the
      main sources for gaining knowledge of structure-activity relationship of natural
      products. Screening for congeners in the extracts of the fermentation broths of
      Streptomyces platensis led to the isolation of platencin A(1), a hydroxy congener
      of platencin. The hydroxylation of the tricyclic enone moiety negatively affected
      the antibacterial activity and appears to be consistent with the hydrophobic
      binding pocket of the FabF. Isolation, structure, enzyme-bound structure and
      activity of platencin A(1) and two other congeners have been described.

PMID- 19581088
TI  - Age-related joint moment characteristics during normal gait and successful
      reactive-recovery from unexpected slip perturbations.
AB  - The objective of the current study was to investigate the effects of aging on 3D
      lower extremity joint moments during successful reactive-recovery from unexpected
      slips. Unexpected slips were induced by having participants walk over a slippery
      floor surface. Successful reactive-recovery trials from nine young and nine
      elderly participants were identified and analyzed. Three-dimensional inverse
      dynamics were implemented to calculate reactive joint moments at the ankle, knee,
      and hip joints. Peak joint moment magnitude and the speed of peak joint moment
      generation were used to describe the balance recovery strategies from unexpected
      slips. Results indicated significantly higher peak joint moments in recovery than
      in normal walking for both the young and elderly. Meanwhile, during reactive
      recovery, the elderly were found to utilize both frontal and sagittal joint
      moments while the younger adults relied primarily on sagittal joint moment. It
      was concluded that the ankle and knee joints were critical in controlling
      sagittal plane motion disturbance, while the hip joint was mainly responsible for
      stabilizing upper body balance in the frontal plane. This study confirmed age
      related differences in joint moment generation during unexpected slips.
      Additionally, implementing 3D analysis is recommended in future slips and falls
      research.

PMID- 19581089
TI  - Mutation analysis of the TATA box-binding protein (TBP) gene in Chinese Han
      patients with spinocerebellar ataxia.
AB  - Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant progressive
      neurodegenerative disease caused by the CAG/CAA expansion in the TATA box-binding
      protein (TBP) gene. This study aimed to assess the frequency of SCA17 in patients
      from mainland China. Analysis of CAG/CAA expansion in this gene was performed in
      263 patients consisting of 100 probands with dominantly inherited ataxias and 163
      patients with sporadic ataxias. Abnormal expansion of CAG/CAA repeats in the
      SCA17 locus was found in a proband and her younger sister. To our knowledge, we
      are providing the first kindred analysis of SCA17 in mainland China.

PMID- 19581090
TI  - Transcortical sensory aphasia following a left frontal lobe infarction probably
      due to anomalously represented language areas.
AB  - A 57-year-old right-handed man presented with speech disturbance 1 day prior to
      his admission. The standardized aphasia test batteries showed transcortical
      sensory aphasia. MRI revealed a left frontal and insular infarct. Positron
      emission tomography scans also revealed a glucose hypometabolism in the same
      region as the infarcted area on MRI. Repeated aphasia testing showed that his
      aphasia only partially improved.

PMID- 19581091
TI  - Vasogenic edema in striatum following ingestion of glufosinate-containing
      herbicide.
AB  - Glufosinate-ammonium (GLA) is a broad-spectrum herbicide used worldwide. We
      report a patient who attempted suicide by ingesting a liquid herbicide containing
      GLA. A diffusion-weighted MRI showed cytotoxic edema in the hippocampus as well
      as vasogenic edema in the striata. To our knowledge, vasogenic edema caused by
      GLA-containing herbicide involving the striatum has not been reported in
      association with cytotoxic edema in the hippocampus. We assume that this
      herbicide affected the central nervous system via different mechanisms to produce
      both cytotoxic and vasogenic edema in the same patient.

PMID- 19581092
TI  - Lymph node metastasis of medulloblastoma in a young adult.
AB  - Medulloblastoma is the commonest primary central nervous system malignancy in
      childhood, but is rare in adults. Rarer still is metastasis of such a tumour to a
      lymph node. This report describes such a case, and briefly discusses relevant
      pathophysiology and epidemiology.

PMID- 19581093
TI  - Stroke presenting under 3 hours in patients younger than 18 years of age.
AB  - We report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one
      of the most significant obstacles to offering acute thrombolytic therapies in
      teenagers and children. Feasibility of treatment is further limited by a lack of
      dosage and safety data in the paediatric population. Improved community awareness
      and more rapid recognition of stroke may reduce lag time to diagnosis.

PMID- 19581094
TI  - The prediction of long-term outcome after subarachnoid hemorrhage as measured by
      the Short Form-36 Health Survey.
AB  - The Glasgow Outcome Scale (GOS) score is widely used to assess outcome after a
      subarachnoid hemorrhage (SAH). Patients who have recovered fully or with a mild
      disability (GOS scores 4 and 5) frequently complain about difficulties in
      conducting their daily activities. The Short Form-36 (SF-36) Health Survey is a
      questionnaire that assesses outcomes in multiple categories. This study was
      conducted to compare the quality of outcome assessment between the SF-36 Health
      Survey and GOS scores. A total of 128 patients with SAH (all data expressed as
      mean+/-standard deviation) aged 53.1+/-12.1 years, and a mean Hunt and Hess grade
      on admission of 2+/-1, were retrospectively included in the study. Medical charts
      were reviewed to assess previous medical history, location of the aneurysm and
      the presence of vasospasm. The SF-36 and GOS scores were collected in structured
      interviews approximately 5 years (+/-2 years) after the SAH. The SF-36 data were
      compared to a historical healthy control cohort of 2,474 individuals. The results
      showed that 52% of patients experienced a favourable outcome after SAH (GOS
      scores 4 and 5). Vasospasm was recorded in 25% of patients. However, the average
      SF-36 results were lower in all tested categories for patients after SAH than the
      healthy normal controls. None of the SF-36 categories except physical function
      correlated significantly with the GOS score. Aneurysm location did not have an
      impact on SF-36 data. Patients after a SAH assessed as GOS score 5 are
      significantly impaired in social functioning and general health. We conclude that
      patients continue to suffer neuropsychological deficits years after a SAH. The
      GOS score is a rough outcome measure that primarily focuses on physical
      functioning. SF-36 is a useful tool to include in the neuropsychological outcome
      assessment of patients with SAH.

PMID- 19581095
TI  - Changes in cerebrospinal fluid nerve growth factor levels during chick embryonic
      development.
AB  - In the early stages of brain development, cells within the ependymal lining of
      the neural tube are thought to secrete cerebrospinal fluid (CSF), the so-called
      neural tube fluid (NTF), whereas before fusion of the neural folds, the
      neuroepithelium that lines the inside of the neural tube is in contact with
      amniotic fluid. As the neural tube closes, a membrane formed from these cells
      invaginates to form the specialized choroid plexus. The choroid plexus is a
      highly vascularized epithelial cell structure that secretes proteins, including
      growth factors, into the CSF. Embryonic CSF (e-CSF) contains high concentrations
      of proteins compared to adult CSF. CSF has been reported to contain nerve growth
      factor (NGF) and other neurotrophic factors. In this study, total protein
      concentration and NGF level in e-CSF samples from chick embryos were measured
      using a dye-based protein assay, enzyme-linked immunosorbent assay (ELISA) and
      Western blot. The total protein concentration and NGF levels in the CSF decreased
      from days E10 to E16. There was a rapid increase in total protein content on days
      E17 and E18, and thereafter the levels decreased from day E19 to day E21. Days
      E17 and E18 coincide with the onset of neuron migration, proliferation and
      organization of the cytoarchitecture of the developing cerebral cortex. After
      that time the total protein concentration and NGF levels decrease until hatching.
      Since CSF is in contact with the cerebral cortical germinal epithelium, changes
      in the protein concentration in the CSF could affect neuroepithelial cell
      proliferation, survival and migration. It is concluded that NGF is not only a
      constant component of CSF during chick embryogenesis but it might also be
      involved in cerebral cortical development.

PMID- 19581096
TI  - Execution accuracy of bone resection and implant fixation in computer assisted
      minimally invasive total knee arthroplasty.
AB  - While computer assisted total knee arthroplasty (TKA) has been documented to
      increase the surgical accuracy in the planning process, there is little
      information about the accuracy in execution processes. We aimed to determine the
      accuracy of execution processes for bone resections and implant fixation in TKAs
      performed with the techniques of computer assisted navigation and minimally
      invasive surgery. Execution deviations, defined as the differences between
      planned targets and executed results, were evaluated for bone resections and
      implant fixation in 107 TKAs. In tibia resection, the mean resection thickness,
      coronal alignment, and sagittal alignment were 0.2mm smaller, 0.3 degrees more
      valgus, 0.3 degrees less posterior slope than the planned, respectively. In femur
      resection, the mean resection thicknesses in the medial and lateral femoral
      condyles, coronal alignment, and sagittal alignment were 0.6mm smaller, 0.8mm
      smaller, 0.1 degrees more varus, and 0.7 degrees less posterior slope than the
      planned, respectively. In implant fixation, the mean coronal alignment and degree
      of extension was 0.7 degrees more valgus and 1.6 degrees decrease than the
      planned, respectively. Only the occurrence of unacceptable executions in implant
      fixation had significant effects on the final coronal alignment. The density of a
      bone and the quality of saw blade had significant effect on the accuracy of bone
      resections. Execution deviations from planned alignment commonly occur in
      computer-assisted minimally invasive TKA, resulting typically from the techniques
      of bone resections and implant fixation, and this information should be
      considered to improve the surgical accuracy of navigated TKAs.

PMID- 19581097
TI  - Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives.
AB  - In the present article, we describe the synthesis, anti-HIV1 profile and
      molecular modeling evaluation of 11 oxoquinoline derivatives. The structure
      activity relationship analysis revealed some stereoelectronic properties such as
      LUMO energy, dipole moment, number of rotatable bonds, and of hydrogen bond
      donors and acceptors correlated with the potency of compounds. We also describe
      the importance of substituents R(2) and R(3) for their biological activity.
      Compound 2j was identified as a lead compound for future investigation due to
      its: (i) high activity against HIV-1, (ii) low cytotoxicity in PBMC, (iii) low
      toxic risks based on in silico evaluation, (iv) a good theoretical oral
      bioavailability according to Lipinski 'rule of five', (v) higher druglikeness and
      drug-score values than current antivirals AZT and efavirenz.

PMID- 19581098
TI  - Urea and carbamate derivatives of primaquine: synthesis, cytostatic and
      antioxidant activities.
AB  - The novel urea primaquine derivatives 3 were prepared by aminolysis of primaquine
      benzotriazolide 2 with several hydroxyamines and ethylendiamine, while carbamates
      4 were synthesized from the same precursor 2 and alcohols. All compounds are
      fully chemically characterized and evaluated for their cytostatic and antioxidant
      activities. The most prominent antiproliferative activity was obtained by
      compounds 3c, 3d, 3g, and 5b (IC(50)=9-40 microM). 1-(5-Hydroxypentyl)-3-[4-(6
      methoxy-quinolin-8-ylamino)-pentyl]urea (3c) showed extreme selectivity toward SW
      620 colon cancer cells (IC(50)=0.2 microM) and a bit less toward lung cancer
      cells H 460. Hydroxyurea 3h showed the highest interaction with DPPH. Primaquine
      twin drug 3g showed very significant inhibition on LOX soybean (IC(50)=62
      microM). Almost all the tested derivatives highly inhibited lipid peroxidation,
      significantly stronger than primaquine phosphate.

PMID- 19581099
TI  - Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as
      inhibitors of Mycobacterium tuberculosis: part 2. Synthesis of rigid pyrazolones.
AB  - Two series of novel rigid pyrazolone derivatives were synthesized and evaluated
      as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of
      tuberculosis. Two of these compounds showed a high activity against MTB (MIC=4
      microg/mL). The newly synthesized pyrazolones were also computationally
      investigated to analyze if their properties fit the pharmacophoric model for
      antitubercular compounds previously built by us. The results are in agreement
      with those reported by us previously for a class of pyrazole analogues and
      confirm the fundamental role of the p-chlorophenyl moiety at C4 in the
      antimycobacterial activity.

PMID- 19581100
TI  - Discovery of novel thiourea derivatives as potent and selective beta3-adrenergic
      receptor agonists.
AB  - In the search for potent and selective human beta3-adrenergic receptor (AR)
      agonists as potential drugs for the treatment of obesity and noninsulin-dependent
      (type II) diabetes, we prepared a novel series of phenoxypropanolamine
      derivatives containing the thiourea moiety and evaluated their biological
      activities at human beta3-, beta2-, and beta1-ARs. Among these compounds, 4
      nitrophenylthiourea (18i) and 3-methoxyphenylthiourea (18k) derivatives were
      found to exhibit potent agonistic activity at the beta3-AR, with EC(50) values of
      0.10 and 0.16 microM, respectively, and no agonistic activity for either the
      beta1- or beta2-AR. In addition, they showed significant hypoglycemic activity in
      a rodent diabetic model.

PMID- 19581101
TI  - Interaction of drug based binuclear mixed-ligand complexes with DNA.
AB  - Here in we tried to increase an antibacterial activity of ciprofloxacin drug due
      to formation of mixed-ligand complexes. Synthesized compounds were found to be
      more potent compare to drugs, ligands and metal salt against selective
      gram((+ve)) and gram((-ve)) organisms. Interaction of the complexes with nucleic
      acid (DNA) were investigated using spectroscopic technique, viscosity measurement
      and gel electrophoresis and it was found that the complexes bind to DNA via
      intercalative mode.

PMID- 19581102
TI  - In vivo imaging of cell morphology and cellular processes in Caenorhabditis
      elegans, using non-linear phenomena.
AB  - We present the detailed imaging of structures and processes of the nematode
      Caenorhabditis elegans (C. elegans) using non-linear microscopy. Complementary
      information about the anatomy of the nematode was collected by implementing a
      combination of two photon excitation fluorescence (TPEF), second and third
      harmonic generation (SHG and THG) image contrast modes on the same microscope.
      Three-dimensional (3D) reconstructions of TPEF, SHG and THG images were also
      performed. Moreover, THG imaging technique has been tested as a potential, novel,
      non-destructive diagnostic tool for monitoring cellular processes in vivo, such
      as neuronal degeneration.

PMID- 19581103
TI  - Detecting myocardial ischaemia using miniature ultrasonic transducers--a
      feasibility study in a porcine model.
AB  - BACKGROUND: Detection of myocardial ischaemia during and after cardiac surgery
      remains a challenge. Echocardiography is more sensitive in ischaemia detection
      than echocardiography (ECG) and haemodynamic monitoring, but demands repeated
      examinations for monitoring over time. We have developed and validated an
      ultrasonic system that permits continuous real-time assessment of myocardial
      ischaemia using miniature epicardial ultrasound transducers. METHODS: In an open
      chest porcine model (n=8), prototype ultrasound transducers were fixed on the
      epicardium in the left anterior descending and circumflex coronary artery supply
      regions, providing continuous measurement of transmural myocardial velocities.
      Peak systolic velocity and post-systolic velocity were recorded simultaneously
      with ECG, left ventricular pressure and arterial pressure. Two-dimensional (2D)
      echocardiographic strain was used as a reference. Global changes were induced by
      infusing fluid, epinephrine, nitroprusside and esmolol. Regional changes were
      induced by occluding the left anterior descending coronary artery (LAD).
      Subsequent LAD stenosis was performed in a subgroup, with flow reduction to 50%
      of baseline level and further to occlusion. RESULTS: Systolic velocity in the LAD
      region decreased during LAD occlusion (0.9+/-0.1 to 0.1+/-0.1 cm s(-1), P<0.01),
      whereas post-systolic velocity increased (0.3+/-0.1 to 2.3+/-0.1 cm s(-1),
      P<0.01). No changes occurred in the circumflex coronary artery (CX) region.
      Severe ischaemia was confirmed by reduction in 2D echocardiography strain
      calculations. Changes in myocardial velocities assessed by miniature transducer
      during ischaemia differed from changes during all global interventions.
      Significant reduction in systolic velocity occurred at 50% LAD flow (0.9+/-0.1 to
      0.5+/-0.1 cm s(-1), P=0.02) with further decrease on following occlusion (0.0+/
      0.0 cm s(-1), P<0.01). Post-systolic velocity increased both from baseline to 50%
      LAD flow, and further to occlusion. CONCLUSION: The epicardial transducers
      provided continuous assessment of regional myocardial function and detected
      ischaemia with high sensitivity and specificity. Further development of this
      system may provide a useful tool for myocardial monitoring during and after
      cardiac surgery.

PMID- 19581104
TI  - Preoperative statin treatment reduces systemic inflammatory response and
      myocardial damage in cardiac surgery.
AB  - OBJECTIVE: To determine if preoperative statin treatment is associated with a
      reduction in systemic inflammatory response (SIR) and myocardial damage markers
      following cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We study a
      prospective cohort of 138 patients who underwent coronary and valvular surgery
      with CPB. We differentiate two study groups: patients with (group A, n=72) or
      without (group B, n=66) statins. Plasma levels of pro-inflammatory interleukins
      (tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-2R),
      creatine phosphokinase (CPK), CPK-MB and troponin I were measured before and 1,
      6, 24 and >72 h after surgery. RESULTS: The baseline, operative and postoperative
      morbidity and mortality characteristics were similar for both the groups. Group A
      had significantly lower postoperative levels of IL-6 than group B at 6h (68.8+/-5
      pg ml(-1) vs 108.9+/-108 pg ml(-1), p=0.01), 24h (71.7+/-7 pg ml(-1) vs 110.4+/
      106 pg ml(-1), p=0.01) and before hospital discharge (21.6+/-12 pg ml(-1) vs
      32.8+/-27 pg ml(-1), p=0.005), as well as significantly lower average IL-6 levels
      in the first 24h following surgery (71.8+/-5 pgml(-1) vs 112.8+/-82 pg ml(-1),
      p=0.002). The postoperative CPK-MB at 24h (19.7+/-23 ng ml(-1) vs 33.1+/-32 ng
      ml(-1), p=0.02) and troponin I levels at the end of the intervention (2.2+/-2.2
      ng ml(-1) vs 3.3+/-3.1 ng ml(-1), p=0.03) and at 24h (4.1+/-3.5 ng ml(-1) vs
      6.6+/-8 ng ml(-1), p=0.04) were also significantly lower in the group treated
      with statins prior to surgery. CONCLUSIONS: Preoperative treatment with statins
      is associated with a lower biochemical parameters of SIR and myocardial damage
      following cardiac surgery with CPB, regardless of it being coronary bypass
      grafting (CABG) or valvular surgery.

PMID- 19581105
TI  - Images in cardio-thoracic surgery. Left atrial myxoma with tumour vascularity:
      three-dimensional images with multi-slice computed tomography.

PMID- 19581106
TI  - Postoperative exostosis of the xiphoid process: a contraindication for precordial
      thump.

PMID- 19581107
TI  - Prospective population-based study comparing quality of life after pneumonectomy
      and lobectomy.
AB  - OBJECTIVE: The impact of type of resection for lung cancer, that is,
      pneumonectomy or lobectomy, on postoperative quality of life is not clearly
      defined. The aim of the study was to compare the changes in health-related
      quality of life in patients undergoing lobectomy or pneumonectomy for lung
      cancer. METHODS: We performed a prospective, population-based, cohort study and
      used a validated quality-of-life instrument to gather information on health
      related quality of life before and 6 months after surgery. The main outcome
      measures were fractional change in the Short Form-36 physical and mental
      component summary scores. RESULTS: There was no statistically significant
      difference in any of the Medical Outcome Study 36-Item Short Form subscales or
      summary scores between the lobectomy (n=101) and pneumonectomy (n=16) group at
      baseline. There was a significant difference in the fractional change in the
      physical component summary score between the lobectomy and pneumonectomy group (
      17% vs -32%, p=0.04), but not in the mental component summary score (6.5% vs 12%,
      p=0.72). CONCLUSIONS: Pneumonectomy had a larger negative impact on the physical
      aspect of health-related quality of life than lobectomy 6 months following
      surgery for lung cancer. The mental component of quality of life was not affected
      by the extent of surgical resection.

PMID- 19581108
TI  - Are we allowed to declare radial artery graft with a 'string sign' for a patent
      conduit?

PMID- 19581110
TI  - Tailoring consumer resources to enhance self-care in chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is associated with high hospitalisation
      and mortality rates and debilitating symptoms. In an effort to reduce
      hospitalisations and improve symptoms individuals must be supported in managing
      their condition. Patients who can effectively self-manage their symptoms through
      lifestyle modification and adherence to complex medication regimens will
      experience less hospitalisations and other adverse events. AIM: The purpose of
      this paper is to explain how providing evidence-based information, using patient
      education resources, can support self-care. DISCUSSION: Self-care relates to the
      activities that individuals engage in relation to health seeking behaviours.
      Supporting self-care practices through tailored and relevant information can
      provide patients with resources and advice on strategies to manage their
      condition. Evidence-based approaches to improve adherence to self-care practices
      in patients with heart failure are not often reported. Low health literacy can
      result in poor understanding of the information about CHF and is related to
      adverse health outcomes. Also a lack of knowledge can lead to non-adherence with
      self-care practices such as following fluid restriction, low sodium diet and
      daily weighing routines. However these issues need to be addressed to improve
      self-management skills. OUTCOME: Recently the Heart Foundation CHF consumer
      resource was updated based on evidence-based national clinical guidelines. The
      aim of this resource is to help consumers improve understanding of the disease,
      reduce uncertainty and anxiety about what to do when symptoms appear, encourage
      discussions with local doctors, and build confidence in self-care management.
      CONCLUSION: Evidence-based CHF patient education resources promote self-care
      practices and early detection of symptom change that may reduce hospitalisations
      and improve the quality of life for people with CHF.

PMID- 19581109
TI  - In vivo molecular evaluation of guinea pig skin incisions healing after surgical
      suture and laser tissue welding using Raman spectroscopy.
AB  - The healing process in guinea pig skin following surgical incisions was evaluated
      at the molecular level, in vivo, by the use of Raman spectroscopy. After the
      incisions were closed either by suturing or by laser tissue welding (LTW),
      differences in the respective Raman spectra were identified. The study determined
      that the ratio of the Raman peaks of the amide III (1247 cm(-1)) band to a peak
      at 1326 cm(-1) (the superposition of elastin and keratin bands) can be used to
      evaluate the progression of wound healing. Conformational changes in the amide I
      band (1633-1682 cm(-1)) and spectrum changes in the range of 1450-1520 cm(-1)
      were observed in LTW and sutured skin. The stages of the healing process of the
      guinea pig skin following LTW and suturing were evaluated by Raman spectroscopy,
      using histopathology as the gold standard. LTW skin demonstrated better healing
      than sutured skin, exhibiting minimal hyperkeratosis, minimal collagen
      deposition, near-normal surface contour, and minimal loss of dermal appendages. A
      wavelet decomposition-reconstruction baseline correction algorithm was employed
      to remove the fluorescence wing from the Raman spectra.

PMID- 19581111
TI  - Associations of circulating TNFalpha and IL-18 with myocardial infarction and
      cardiovascular risk markers: the Glasgow Myocardial Infarction Study.
AB  - BACKGROUND: There are a lack of data on the associations of circulating levels of
      TNFalpha and IL-18 with myocardial infarction (MI), and on the extent of
      confounding by classical and inflammatory risk markers. METHODS: We measured
      TNFalpha and IL-18 in plasma from 446 MI cases and 477 age- and sex-matched
      controls from North Glasgow. RESULTS: TNFalpha and IL-18 were elevated in cases
      compared to controls (TNFalpha medians 0.99 pg/ml [interquartile range 0.65-1.64
      pg/ml] versus 0.77 pg/ml [0.52-1.22 pg/ml], p<0.0001; IL-18 medians 287 pg/ml
      [212-404 pg/ml] versus 271 pg/ml [200-373 pg/ml], p=0.01). IL-18 was moderately
      associated with HDL cholesterol r=-0.22, triglycerides r=0.16, and BMI r=0.14 (p
      for all < or =0.003) in the control population, but not among cases. TNFalpha had
      few associations with classical risk factors among cases or controls. TNFalpha
      had a significant association with MI: odds ratio (OR) 1.66 (95% confidence
      interval; 1.10-2.50), comparing extreme thirds after adjusting for classical risk
      factors, which was reduced on further adjustment for other inflammatory markers
      (OR 1.47; 0.91-2.37). IL-18 showed no association by thirds after adjustment for
      classical risk factors (OR 1.07; 0.70-1.62). CONCLUSIONS: Circulating levels of
      IL-18 and TNFalpha were elevated in those with previous MI, but only TNFalpha
      retained an association after adjustment for classical risk factors.
      Independently elevated TNFalpha among those with previous MI may reflect cardiac
      expression of TNFalpha in ongoing myocardial remodeling.

PMID- 19581112
TI  - Seizures in encephalitis: predictors and outcome.
AB  - BACKGROUND: Seizures are common in encephalitis but there is paucity of
      comprehensive studies evaluating predictors of seizures. AIM: To evaluate the
      frequency and predictors of seizures in encephalitis patients and its effect on
      outcome. METHODS: In a prospective hospital based study, the patients with
      encephalitis were evaluated clinically and presence of seizure, its type and
      duration were noted. Patients' consciousness was assessed by Glasgow coma scale
      (GCS) score and neurological findings were recorded. Blood count, serum
      chemistry, electroencephalography (EEG), cranial MRI and CSF examination were
      done. The diagnosis of encephalitis was based on ELISA and PCR and grouped into
      herpes, Japanese, dengue and nonspecific encephalitis. Hospital mortality and 3
      month outcome were noted. RESULTS: 148 patients with encephalitis whose median
      age was 26 (range 1-75) years were included. Seizures occurred in 63 (42.6%)
      patients; 18 of whom had status epilepticus. Seizures were more common in herpes
      (75%) followed by Japanese (54%) encephalitis. The predictors of seizure in
      encephalitis were age, GCS score and cortical involvement on MRI. 61% children
      had seizures compared to 36.6% adults and 53.3% with cortical involvement on MRI
      had seizure compared to 14.3% without. Seizures were not related to mortality but
      associated with poor outcome. CONCLUSION: In encephalitis, seizures occur in
      42.6% patients especially in children with low GCS score and having cortical
      involvement on MRI.

PMID- 19581113
TI  - Measurement of one and two bond N-C couplings in large proteins by TROSY-based J
      modulation experiments.
AB  - Residual dipolar couplings (RDCs) between NC' and NC(alpha) atoms in polypeptide
      backbones of proteins contain information on the orientation of bond vectors that
      is complementary to that contained in NH RDCs. The (1)J(NC)(alpha) and
      (2)J(NC)(alpha) scalar couplings between these atoms also display a Karplus
      relation with the backbone torsion angles and report on secondary structure.
      However, these N-C couplings tend to be small and they are frequently
      unresolvable in frequency domain spectra having the broad lines characteristic of
      large proteins. Here a TROSY-based J-modulated approach for the measurement of
      small (15)N-(13)C couplings in large proteins is described. The cross-correlation
      interference effects inherent in TROSY methods improve resolution and signal to
      noise ratios for large proteins, and the use of J-modulation to encode couplings
      eliminates the need to remove frequency distortions from overlapping peaks during
      data analysis. The utility of the method is demonstrated by measurement of
      (1)J(NC'), (1)J(NC)(alpha) , and (2)J(NC)(alpha) scalar couplings and (1)D(NC')
      and D(NC)(alpha) residual dipolar couplings for the myristoylated yeast
      ARF1.GTPgammas protein bound to small lipid bicelles, a system with an effective
      molecule weight of approximately 70kDa.

PMID- 19581114
TI  - Cryogenic 35GHz pulse ENDOR probehead accommodating large sample sizes:
      Performance and applications.
AB  - The construction and performance of a cryogenic 35GHz pulse electron nuclear
      double resonance (ENDOR) probehead for large samples is presented. The resonator
      is based on a rectangular TE(102) cavity in which the radio frequency (rf) B(2)
      field is generated by a two turn saddle ENDOR coil crossing the resonator along
      the sample axis with minimal distance to the sample tube. An rf power efficiency
      factor is used to define the B(2)-field strength per square-root of the
      transmitted rf power over the frequency range 2-180MHz. The distributions of the
      microwave B(1)- and E(1)-field, and the rf B(2)-field are investigated by
      electromagnetic field calculations. All dielectrics, the sample tube, and
      coupling elements are included in the calculations. The application range of the
      probehead and the advantages of using large sample sizes are demonstrated and
      discussed on a number of paramagnetic samples containing transition metal ions.

PMID- 19581115
TI  - Visualization of enantiomers using natural abundant (13)C-filtered single and
      double quantum selective refocusing experiments: Application to small chiral
      molecules.
AB  - The routine use of proton NMR for the visualization of enantiomers, aligned in
      the chiral liquid crystal solvent poly-gamma-benzyl-l-glutamate (PBLG), is
      restricted due to severe loss of resolution arising from large number of pair
      wise interaction of nuclear spins. In the present study, we have designed two
      experimental techniques for their visualization utilizing the natural abundance
      (13)C edited selective refocusing of single quantum (CH-SERF) and double quantum
      (CH-DQSERF) coherences. The methods achieve chiral discrimination and aid in the
      simultaneous determination of homonuclear couplings between active and passive
      spins and heteronuclear couplings between the excited protons and the
      participating (13)C spin. The CH-SERF also overcomes the problem of overlap of
      central transitions of the methyl selective refocusing (SERF) experiment
      resulting in better chiral discrimination. Theoretical description of the
      evolution of magnetization in both the sequences has been discussed using
      polarization operator formalism.

PMID- 19581116
TI  - Electronic characterization of lithographically patterned microcoils for high
      sensitivity NMR detection.
AB  - Nuclear magnetic resonance (NMR) offers a non-destructive, powerful, structure
      specific analytical method for the identification of chemical and biological
      systems. The use of radio frequency (RF) microcoils has been shown to increase
      the sensitivity in mass-limited samples. Recent advances in micro-receiver
      technology have further demonstrated a substantial increase in mass sensitivity
      [D.L. Olson, T.L. Peck, A.G. Webb, R.L. Magin, J.V. Sweedler, High-resolution
      microcoil H-1-NMR for mass-limited, nanoliter-volume samples, Science 270 (5244)
      (1995) 1967-1970]. Lithographic methods for producing solenoid microcoils possess
      a level of flexibility and reproducibility that exceeds previous production
      methods, such as hand winding microcoils. This paper presents electrical
      characterizations of RF microcoils produced by a unique laser lithography system
      that can pattern three dimensional surfaces and compares calculated and
      experimental results to those for wire wound RF microcoils. We show that existing
      optimization conditions for RF coil design still hold true for RF microcoils
      produced by lithography. Current lithographic microcoils show somewhat inferior
      performance to wire wound RF microcoils due to limitations in the existing
      electroplating technique. In principle, however, when the pitch of the RF
      microcoil is less than 100mum lithographic coils should show comparable
      performance to wire wound coils. In the cases of larger pitch, wire cross
      sections can be significantly larger and resistances lower than microfabricated
      conductors.

PMID- 19581117
TI  - Transcobalamin II deficiency at birth.
AB  - Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited
      disorder of cobalamin transport that leads to intracellular cobalamin depletion
      with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase
      activities. Affected individuals may suffer from long-term neurological sequelae
      if therapy with intramuscular hydroxocobalamin is not initiated promptly. We
      report two sisters with complete absence of transcobalamin due to homozygosity
      for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop
      codon and non-functional protein. The older sister, now 4.5 years old, presented
      at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly
      declining clinical course. Prompt therapy with 1mg hydroxocobalamin/day led to
      full recovery within days. Her now 1.5 year old sister was diagnosed shortly
      after birth and was started on hydroxocobalamin prior to onset of clinical
      symptoms. Interestingly, urinary methylmalonic acid excretion was increased
      significantly during the first days of life suggesting that functional cobalamin
      deficiency is present also during fetal life, although not giving rise to
      clinical symptoms until well after birth.

PMID- 19581118
TI  - Infectious complications in patients with acute myeloid leukemia treated
      according to the protocol with daunorubicin and cytarabine with or without
      addition of cladribine. A multicenter study by the Polish Adult Leukemia Group
      (PALG).
AB  - OBJECTIVES: The addition of cladribine to the standard regimen consisting of
      daunorubicin and cytarabine has been reported to increase the efficacy of
      induction therapy in acute myeloid leukemia (AML). The goal of this study was to
      determine the effect of this modification on the incidence and spectrum of
      infectious complications. METHODS: Case report forms of 309 patients with newly
      diagnosed AML who had been enrolled in the prospective, randomized 'DAC-7 vs. DA
      7' trial were reviewed. The frequency, etiology, localization, severity, and
      outcome of infections were compared for patients receiving only daunorubicin and
      cytarabine (DA-7) and those additionally treated with cladribine (DAC-7).
      RESULTS: A total of 443 febrile episodes were reported with no significant
      difference between the treatment groups. A trend towards a higher frequency of
      bacteremias was observed among DA-7 patients compared to those in the DAC-7 group
      (31% vs. 21%; p=0.08). The treatment arms did not differ in terms of the
      distribution of the isolated Gram-positive, Gram-negative, fungal, and viral
      organisms. However, when bacteremias were considered, Gram-positive blood
      cultures tended to be more frequent in the DA-7 compared to the DAC-7 group (16%
      vs. 8.5%; p=0.07). This difference reached statistical significance when major
      blood bacteremias were analyzed separately (13% vs. 5%; p=0.02). Complete
      recovery from infections was observed in the majority of patients across both
      treatment arms and no significant difference was noted regarding infection
      related mortality. CONCLUSIONS: The addition of cladribine to standard induction
      chemotherapy has no impact on the incidence and spectrum of infectious
      complications in newly diagnosed AML patients.

PMID- 19581119
TI  - Design and test of hip stem for medullary revascularization.
AB  - This study aims at developing a femoral stem which maintains appropriate
      mechanical properties for clinical use and provides enough medullary space for
      revascularization. Hollow and drilled stems were designed to gain sufficient
      medullary space. Three-dimensional finite element models of the hollow stems were
      built including the hollow parameters of different wall thicknesses, bore depths
      and transverse hole patterns. The effects of these parameters on stress under
      load bearing were investigated. The results indicated that the effects of
      thickness on the stem depended on their location along the stem. The hollow depth
      should be designed as deep as possible to ensure a smooth change of cross
      sectional area and avoid unexpected stress concentrations. The transverse hole
      pattern must be arranged very carefully to avoid high stress concentrations. Then
      the proper parameters of hollow stem were determined. Through the above
      processes, the appropriate shape of femoral stem for medullary revascularization
      was determined as a hollow structure with gradually changing thickness and a
      distinct hole pattern. Fatigue tests were conducted on three prototypes, which
      all three prototypes passed. The finite element models and design processes were
      therefore proved useful for our purpose.

PMID- 19581120
TI  - The diverse behaviour of the P-Cl bonds in the spiro-cis-ansa spermidine
      derivative cyclotriphosphazene towards mono-functional nucleophilic reagents.
AB  - A number of new spiro-ansa spermidine derivative cyclotriphosphazenes (2-10) is
      synthesized in order to provide insight into the reaction mechanism for
      nucleophilic substitution. The structures of the compounds were determined by
      elemental analysis, mass (MS), (1)H, (19)F (for 9) and (31)P NMR spectroscopies.
      Compounds (2-8) and 9, 10 can be formed by a proton abstraction-chloride
      elimination and both the S(N)(1) and S(N)(2) reaction mechanisms, respectively.

PMID- 19581121
TI  - Ab initio, density functional theory and structural studies of 4-amino-2
      methylquinoline.
AB  - The Fourier transform infrared (FTIR) and FT-Raman spectra of 4-amino-2
      methylquinoline (AMQ) have been recorded in the range 4000-400 and 4000-100 cm(
      1), respectively. The experimental vibrational frequency was compared with the
      wavenumbers obtained theoretically by ab initio HF and DFT-B3LYP gradient
      calculations employing the standard 6-31 G** and high level 6-311 ++G** basis
      sets for optimised geometry of the compound. The complete vibrational assignment
      and analysis of the fundamental modes of the compounds were carried out using the
      experimental FTIR and FT-Raman data, and quantum mechanical studies. The geometry
      and normal modes of vibration obtained from the HF and DFT methods are in good
      agreement with the experimental data. The potential energy distribution of the
      fundamental modes was calculated with ab initio force fields utilising Wilson's
      FG matrix method. The NH-pi interactions and the influence of amino and methyl
      groups on the skeletal modes are investigated.

PMID- 19581122
TI  - Applications of several spectral techniques to characterize coordination
      compounds derived from 2,6-diacetylpyridine derivative.
AB  - The coordination compounds of Cr(III), Mn(II) and Co(II) metal ions derived from
      quinquedentate 2,6-diacetylpyridine derivative have been synthesized and
      characterized by using the various physicochemical studies like stoichiometric,
      molar conductivity and magnetic, and spectral techniques like IR, NMR, mass, UV
      and EPR. The general stoichiometries of the complexes are found to be
      [Cr(H(2)L)X] and [M(HL)X], where M=Mn(II) and Co(II); H(2)L=dideprotonated
      ligand, HL=monodeprotonated ligand and X=NO(3)(-), Cl(-) and OAc(-). The studies
      reveal that the complexes possess monomeric compositions with six coordinated
      octahedral geometry (Cr(III) and Mn(II) complexes) and six coordinated tetragonal
      geometry (Co(II) complexes).

PMID- 19581123
TI  - Multiplex binding modes of toluidine blue with calf thymus DNA and conformational
      transition of DNA revealed by spectroscopic studies.
AB  - It is noteworthy to understand the details of interactions between antitumor
      drugs and DNA because the binding modes and affinities affect their antitumor
      activities. Here, The interaction of toluidine blue (TB), a potential antitumor
      drug for photodynamic therapy of tumor, with calf thymus DNA (ctDNA) was explored
      by UV-vis, fluorescence, circular dichroism (CD) spectroscopy, UV-melting method
      and surface-enhance Raman spectroscopy (SERS). The experimental results suggest
      that TB could bind to ctDNA via both electrostatic interaction and partial
      intercalation. The fluorescence quenching of TB by ctDNA was static and due to
      electron transfer from bases to the excited singlet state of TB. At low
      [TB]/[DNA] ratio, TB mainly partially intercalated into ctDNA resulting in the
      slight increase of base stacking degree; at high [TB]/[DNA] ratio, excessive TB
      externally stacked along the helix surface via coupling with partially
      intercalated ones, thereby inducing B-A transition of ctDNA. The conformational
      transition of DNA was confirmed by the obvious improvement of the thermal
      stability of ctDNA. The SERS spectra suggest that TB could partially intercalate
      into DNA basepairs with its ring C(1)NC(1') side buried.

PMID- 19581124
TI  - Molecular structure, spectroscopic studies and first-order molecular
      hyperpolarizabilities of ferulic acid by density functional study.
AB  - Quantum chemical calculations of energies, geometrical structure and vibrational
      wavenumbers of ferulic acid (FA) (4-hydroxy-3-methoxycinnamic acid) were carried
      out by using density functional (DFT/B3LYP/BLYP) method with 6-31 G(d,p) as basis
      set. The optimized geometrical parameters obtained by DFT calculations are in
      good agreement with single crystal XRD data. The vibrational spectral data
      obtained from solid phase FT-IR and FT-Raman spectra are assigned based on the
      results of the theoretical calculations. The observed spectra are found to be in
      good agreement with calculated values. The electric dipole moment (micro) and the
      first hyperpolarizability (beta) values of the investigated molecule have been
      computed using ab initio quantum mechanical calculations. The calculation results
      also show that the FA molecule might have microscopic nonlinear optical (NLO)
      behavior with non-zero values. A detailed interpretation of the infrared and
      Raman spectra of FA was also reported. The energy and oscillator strength
      calculated by time-dependent density functional theory (TD-DFT) results
      complements with the experimental findings. The calculated HOMO and LUMO energies
      shows that charge transfer occur within the molecule. The theoretical FT-IR and
      FT-Raman spectra for the title molecule have been constructed.

PMID- 19581125
TI  - Human rhinovirus C associated with wheezing in hospitalised children in the
      Middle East.
AB  - BACKGROUND: Few studies have investigated the disease burden and genetic
      diversity of human rhinoviruses (HRVs) in developing countries. OBJECTIVES: To
      assess the burden of HRV in Amman, Jordan, and to characterise clinical
      differences between HRV groups. STUDY DESIGN: We prospectively studied children
      <5 years, hospitalised with respiratory symptoms and/or fever in Amman, Jordan.
      Viruses were identified by real-time reverse transcriptase polymerase chain
      reaction (RT-PCR). VP4/VP2 gene sequencing was performed on HRV-positive
      specimens. RESULTS: Of the 728 enrolled children, 266 (37%) tested positive for
      picornaviruses, 240 of which were HRV. Of the HRV-positive samples, 62 (26%) were
      of the recently identified group HRVC, 131 (55%) were HRVA and seven (3%) were
      HRVB. The HRVC strains clustered into at least 19 distinct genotypes. Compared
      with HRVA-infected children, children with HRVC were more likely to require
      supplemental oxygen (63% vs. 42%, p=0.007) and, when co-infections were excluded,
      were more likely to have wheezing (100% vs. 82%, p=0.016). CONCLUSIONS: There is
      a significant burden of HRV-associated hospitalisations in young children in
      Jordan. Infection with the recently identified group HRVC is associated with
      wheezing and more severe illness.

PMID- 19581126
TI  - Biophysical techniques for ligand screening and drug design.
AB  - Biophysical methods are currently involved in drug design in two ways: the
      qualitative detection of small molecule binding to a target (hit identification),
      and the quantitative determination of physical parameters associated to binding
      (hit-to-lead progression). In the first case, efforts have been made toward
      miniaturization, automation, and speed-up of the screening process allowing a
      higher throughput. In the second one, sophisticated applications have been
      developed to derive detailed relevant information. Preferably, several methods
      are used in combination to avoid bias and/or limitations associated with a single
      one, often together with computational methods. New developments should allow
      important systems overlooked so far to be studied: membrane proteins,
      intrinsically unstructured proteins, as well as in-cell studies.

PMID- 19581127
TI  - Molecular therapies for heritable blistering diseases.
AB  - Tremendous progress has been made over the past two decades in understanding the
      molecular genetics of heritable skin diseases. The paradigm for such conditions
      is epidermolysis bullosa (EB), which comprises a group of heritable blistering
      disorders caused by mutations in ten genes expressed in the cutaneous basement
      membrane zone and has high morbidity and mortality. Identification of distinct
      mutations has improved the diagnosis and subclassification of EB, leading to
      improvements in disease prognosis, and has provided a basis for prenatal and pre
      implantation genetic diagnosis for this disorder. Nevertheless, there is no cure
      or effective treatment for EB. Here, we review recent exciting developments in
      the areas of molecular therapies, including gene therapy, protein replacement
      therapy and bone-marrow-derived stem cell transfer, as potential new avenues to
      treat EB and other currently intractable heritable skin diseases.

PMID- 19581128
TI  - Type II transmembrane serine proteases in cancer and viral infections.
AB  - Regulated proteolysis of cellular factors is pivotal to tissue development and
      homeostasis, whereas uncontrolled proteolytic activity is linked to disease. Type
      II transmembrane serine proteases (TTSPs) are expressed at the cell surface and
      are thus ideally located to regulate cell-cell and cell-matrix interactions.
      Increasing evidence demonstrates that aberrant expression of TTSPs is a hallmark
      of several cancers and recent studies have defined molecular mechanisms
      underlying TTSP-promoted carcinogenesis. In addition, new findings suggest that
      influenza and other respiratory viruses could exploit TTSPs to promote their
      spread, making these proteases potential targets for intervention in cancer and
      viral infections. Here, we review the role of TTSPs in tumorigenesis and viral
      infection and discuss potential approaches to therapy.

PMID- 19581129
TI  - Prognostic value of serum creatinine levels in children with posterior urethral
      valves treated by primary valve ablation.
AB  - PURPOSE: We evaluated the prognostic value of serum creatinine level at
      presentation and nadir creatinine during follow up for future renal function (RF)
      in children with posterior urethral valves (PUV). MATERIALS AND METHODS: Between
      1987 and 2004, 120 cases of PUV were treated initially at our hospital with valve
      ablation. Initial assessment included serum creatinine measurement, urine
      analysis and culture, renal ultrasonography and voiding cystourethrography. After
      valve ablation, renal ultrasound and serum creatinine measurement were repeated
      and thereafter during visits until the end of follow up. RESULTS: Follow up
      ranged from 2 to 12 years (mean=4.4). Renal insufficiency (RI) developed at the
      end of follow up in 44 patients (36.5%). The mean initial and nadir serum
      creatinine in the RI group was higher than in the normal RF group (P<0.05). With
      a cut-off value of 1mg/dl for initial and nadir serum creatinine, the incidence
      of RI was significantly different (P<0.05). CONCLUSION: Our data confirm the high
      prognostic value of nadir serum creatinine after relief of valvular obstruction.
      Further, the serum creatinine level before valve ablation correlates
      significantly with long-term RF in children with PUV.

PMID- 19581130
TI  - The mammalian sympathetic prevertebral ganglia: models for the study of neuronal
      networks and basic neuronal properties.
AB  - The mammalian sympathetic prevertebral ganglia regulate various visceral
      functions and in particular the digestive tract motility. Several integrative
      properties of these ganglia have been described: convergence of central inputs,
      projection of visceral inputs at the pre- and post synaptic level and pacemaker
      activity of the neurones. This review presents the results obtained on another
      integrative property which has been widely studied over the last 10 years: the
      modulation of the fast central inputs by neuromodulators such as nitric oxide,
      ceramide and GABA. These substances facilitate or inhibit the fast central inputs
      through complex interrelated actions. We also present striking results recently
      obtained during the study of a regulatory reflex of the digestive tract motility
      organized by the prevertebral ganglia: the gastro-duodenal inhibitory reflex.
      During this reflex, the neurotransmitter released by the visceral afferent fibres
      to activate the ganglionic neurones is gaseous: nitric oxide. Moreover, the
      mechanism conducting the excitation along the afferent and efferent fibres is
      independent of action potentials. This mechanism requires the integrity of the
      membrane lipid rafts and the activation in cascade of the following second
      messenger sequence: ceramide, calcium, nitric oxide and guanosine 3', 5'-cyclic
      monophosphate. The existence of this mechanism gives grounds for rethinking one
      of the central dogmas in neuroscience according to which excitation is only
      conducted along nerves by an electrical phenomenon, the action potential. All
      these results strengthen the role of the prevertebral ganglia as a model for the
      study of neuronal networks and basic neuronal properties.

PMID- 19581133
TI  - Anatomical study of latissimus dorsi musculocutaneous flap vascular distribution.
AB  - BACKGROUND: The objective of the current study is to elucidate the three
      dimensional vascular distribution as far as the peripheral areas of a latissimus
      dorsi musculocutaneous flap and to establish a safe procedure for creating it.
      METHODS: A lead oxide with gelatin-contrast agent was injected into fresh
      cadavers and the angiosomes in the muscle and skin were examined in detail.
      RESULTS: In the muscle, three vascular territories were observed. The first
      vascular territory was formed by the thoracodorsal artery, the perforating
      branches of the ninth intercostal artery and those of the tenth intercostal
      artery located in the lateral part of the muscle. The second vascular territory
      was formed by the perforating branches of the tenth intercostal artery located in
      the medial part of the muscle, those of the 11th intercostal artery and the
      subcostal artery. The third vascular territory was formed by perforating branches
      of the first and second lumbar arteries. In the dorsal skin above the muscle, two
      vascular territories were observed. The first vascular territory was formed by
      perforating cutaneous branches of the thoracodorsal artery, perforating branches
      of the ninth through 11th intercostal arteries and the scapular circumflex
      artery. The second vascular territory was formed by perforating branches of the
      subcostal artery and the first and second lumbar arteries. CONCLUSIONS: When
      using a latissimus dorsi musculocutaneous flap with the thoracodorsal artery as a
      pedicle, the flap can be safely elevated as far as the inferior border of the
      12th rib where perforating branches of the subcostal artery are distributed. At
      the same time, skin above the muscle can be safely harvested up to the iliac
      crest. It is essential, however, that the skin paddle includes perforating
      branches of the ninth intercostal artery or perforating branches of the 10th
      intercostal artery in the lateral part of the muscle.

PMID- 19581134
TI  - Vacuum-assisted closure therapy in newborn gangrene.
AB  - Gangrene of the newborn or neonatal gangrene is very uncommon, and it usually
      involves the extremities. Neonatal gangrene seems to be more frequent in
      pregnancies related with spontaneous rupture of the amniotic sac leading to
      delayed delivery or dry labour. However, in most of the cases, no aetiological
      factor can be found. Foetal pressure necrosis and amniotic band sequence are two
      of the most common causes of this condition.Thrombosis, emboli, congenital heart
      disease, coagulopathy, sepsis and polycythaemia are some of the other aetiologic
      factors. Treatment of this condition is usually conservative and supportive.
      Conservative treatment includes adequate hydration, prevention from infections
      and allowing the involved area to demarcate in an aseptic environment. In some
      cases, surgical debridement and further reconstruction can be necessary. In order
      to prepare the wound bed for surgical closure after surgical debridement, vacuum
      assisted closure (VAC) therapy can be a new, highly effective method in the
      treatment of newborn gangrene. In this article, a case of a neonatal gangrene
      treated with the application of VAC therapy is presented.

PMID- 19581131
TI  - Endocytosis, asymmetric cell division, stem cells and cancer: unus pro omnibus,
      omnes pro uno.
AB  - Carcinogenesis can be initiated in adult stem cells, suggesting that tumours
      arise as a consequence of stem-cell dysfunction. In the fruitfly, cancer arises
      in stem cells that fail to undergo asymmetric cell division. In flies and
      mammals, a specific regulation of the endocytic trafficking machinery allows stem
      cells to self-renew and generate the differentiating cells required to form and
      maintain mature organs. We review recent findings suggesting that an
      understanding of the relationship between endocytosis, asymmetric cell division,
      stem cells and cancer will be crucial to unravel the cell biological basis of
      tumourigenesis.

PMID- 19581135
TI  - Reverse Yus flap for upper lip reconstruction.

PMID- 19581137
TI  - Surgical tip: Simple technique for harvesting split thickness skin grafts from
      degloved skin.

PMID- 19581138
TI  - Gastroprotective strategy in aspirin users.

PMID- 19581136
TI  - Reconstruction of the buccal mucosa following release for submucous fibrosis
      using two radial forearm flaps from a single donor site.
AB  - BACKGROUND: Oral submucous fibrosis is a collagen disorder affecting the
      submucosal layer and can severely limit mouth opening. The use of bilateral
      forearm flaps to fill buccal defects following trismus release has proven to be
      effective and reliable. However, it requires the sacrifice of radial arteries
      from both forearms. We have developed a technique that allows for the harvest of
      two independent flaps from a single forearm donor site. METHODS: Two separate
      flaps are designed on the same radial artery and concomitant vein pedicle. The
      distal flap is marked in the standard fashion and the proximal skin paddle is
      designed in the middle third of the forearm, based on septocutaneous branches of
      the radial artery. The two flaps are elevated and subsequently divided into two
      independent free flaps. Between June 2004 and June 2007, a total of 16 flaps were
      harvested from eight donor sites for buccal mucosa defects following trismus
      release. Improvements in mouth opening and buccal pliancy were evaluated by
      comparing preoperative and postoperative inter-incisal distance (IID) and maximal
      mouth capacity. RESULTS: All flaps survived completely, and all donor sites were
      closed primarily, except for one. The mean flap size was 6.6x2.6cm (range:
      6x2.5cm-7x3cm), mean pedicle length was 5.7cm, mean ischaemia time was 46min and
      mean total operating time was 8h 45min. At an average of 19.8 months follow-up,
      the inter-incisal distance averaged 29.13mm, an increase of 20.88mm compared with
      the preoperative measurement. The maximal mouth capacity averaged 55.63cc, an
      increase of 9.38cc compared with the preoperative measurement. CONCLUSION: Two
      independent small flaps can be harvested safely from one radial forearm donor
      site. This approach is a useful option for reconstruction of bilateral buccal
      defects, particularly following submucous fibrosis release. The donor-site
      morbidity is minimal and limited to one forearm.

PMID- 19581139
TI  - Retrogenes in preimplantation embryo development: a unique mode of
      transcriptional regulation.
AB  - Our studies show that retrogenes are preferentially expressed in preimplantation
      embryos. These genes carry a short noncoding exon 1 that contributes directly to
      expression of the gene, and a second exon that contains the coding sequence
      without intron interruption. We show that preimplantation gene expression is
      first regulated by developmentally regulated transcription factors that target
      exon 1 and the solitary intron, followed by promoter hypermethylation on
      implantation and in adult tissues. An understanding of the mechanisms of gene
      expression during preimplantation development should have an impact on the
      understanding and treatment of spontaneous abortion and infertility.

PMID- 19581140
TI  - Reconstruction of the hypopharynx after surgical treatment of squamous cell
      carcinoma.
AB  - Squamous cell carcinoma of the hypopharynx (HPSCC) tends to present with an
      advanced stage. Surgery with postoperative radiation or chemoradiation therapy
      has been the standard treatment for HPSCC. Radical surgery may result in a large
      surgical defect of the hypopharyngeal and cervical esophageal regions.
      Reconstruction of the surgical defect is also important after ablation
      procedures. Many reconstructive methods have been developed. However, each method
      has its own advantages and disadvantages. The ideal method for hypopharyngeal
      reconstruction should have the following attributes if possible: single-stage
      procedure, high success rate of tissue transfer, low donor-site morbidity, low
      fistula and stenosis rates, restoration of the ability to speak and swallow, able
      to achieve successful reconstruction in a heavily radiated area and tolerance of
      postoperative radiotherapy. In this review article, we discuss the indications
      and drawbacks of several reconstructive methods that have been frequently used in
      our clinical practice. Finally, we will introduce the technique of
      laryngotracheal flap reconstruction, which was developed in our institution and
      has proved to be a simple and reliable method for hypopharyngeal reconstruction.

PMID- 19581141
TI  - Use of gastroprotective drugs in patients receiving low-dose aspirin.
AB  - BACKGROUND: Low-dose aspirin is widely used for prevention of stroke, heart
      attacks, and death in patients with atherothrombotic disease, but its use is
      associated with serious gastrointestinal (GI) adverse effects. Gastroprotective
      drugs (GPDs) have been used to reduce aspirin-related GI complications but are
      usually underutilized. The aim of this study was therefore to determine the
      prescription pattern of GPDs with low-dose aspirin therapy. METHODS: All patients
      who had attended general and specialist outpatient clinics of Tung Wah Hospital
      between September 1, 2007 and September 30, 2007 and received low-dose aspirin
      therapy were included in the study. Data were collected through retrospective
      chart review and recorded on a standardized data collection form. Univariate
      analysis was performed using chi2 tests for discrete variables. Factors that
      might be associated with prescription of GPD with low-dose aspirin were assessed
      in multiple logistic regression models. RESULTS: Three hundred and three patients
      were included in this study, and the rate of GPD prescription was 48.5%. Most of
      the patients received H2-receptor antagonist, and, to a lesser degree, antacid
      and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much
      more likely to be co-prescribed GPD than those who had no history of GI disorders
      (OR, 26.5). Compared with patients who were managed in general outpatient clinic,
      those managed in specialist clinic were more likely to receive GPD (OR, 3.04).
      CONCLUSION: The prescription rate of GPD with aspirin is low. Also, it seems that
      physicians are unaware of the risk factors related to aspirin-induced GI
      complications.

PMID- 19581142
TI  - Common hemoglobin variants in southern Taiwan and their effect on the
      determination of HbA1c by ion-exchange high-performance liquid chromatography.
AB  - BACKGROUND: Patients with hemoglobin (Hb) variants may produce false HbA1c
      measurement. This study aimed to detect the common Hb variants in southern Taiwan
      and to evaluate their effect on the determination of HbA1c. METHODS: A total of
      1,434 samples collected for HbA1c measurement at Kaohsiung Veterans General
      Hospital in southern Taiwan in March 2008 were submitted for Hb variant analysis
      by Primus CLC-385. HbA1c measurements were obtained using ion-exchange high
      performance liquid chromatography (HPLC) (Tosoh HLC-723 G7) for routine analysis.
      Patients identified with Hb variants were recalled for boronate-affinity HPLC
      analysis. The values of estimated average glucose (eAG) were converted from
      HbA1c. Values of eAG-FPG, calculated by eAG minus fasting plasma glucose (FPG),
      were compared to estimate the accuracy of HbA1c measurement in patients with Hb
      variants. RESULTS: Among the 1,434 patients, the mean standard deviation of FPG
      was 162.8 +/- 60.5 mg/dL, HbA1c was 8.28 +/- 1.97%, and eAG was 190.9 +/- 56.6
      mg/dL. Five Hb variants were detected in 11 patients, the incidence being 0.76%.
      Hb J was identified in 4 patients, Hb G in 2 patients, Hb E in 1 patient, Hb
      owari in 3 patients, and high fetal hemoglobin (HbF) in 1 patient. Abnormal HPLC
      chromatograms were seen among the patients with Hb J, E, G and HbF, but not in
      the patients with Hb owari. In patients with Hb variants, FPG was 149.5 +/- 39.9
      mg/dL, HbA1c was 7.29 +/- 2.01%, and eAG was 162.5 +/- 57.7 mg/dL. Lower values
      of eAG-FPG may have occurred in the patients with Hb J and E, and in those with
      high HbF. On scattergrams of the relationship between HbA1c and FPG, the plots of
      Hb J, E and high HbF lay below the regression line of non-Hb variants.
      Inconsistent Hb values between both methods were only observed among some samples
      of patients with Hb variants. CONCLUSION: The existence of Hb variants may result
      in false HbA1c measurement. The possible presence of spuriously low HbA1c levels
      or abnormal HPLC chromatograms by using ion-exchange methods should be kept in
      mind.

PMID- 19581143
TI  - Potential function of amniotic fluid in fetal development---novel insights by
      comparing the composition of human amniotic fluid with umbilical cord and
      maternal serum at mid and late gestation.
AB  - BACKGROUND: Amniotic fluid (AF) is a dynamic and complex mixture. Up to now,
      little is known about the physiological functions of AF in the process of fetal
      development. We suppose that AF carries components such as proteins or peptides,
      which contribute to the regulation of fetal development. METHODS: Compositions
      including biochemical components and tumor markers were determined in human AF,
      umbilical cord serum (UCS) and maternal serum (MS) from the same subject in the
      range of 15-42 weeks of gestation. RESULTS: (1) The levels of primary
      electrolytes such as sodium, chloride, anion gap and osmotic pressure in AF was
      almost the same as in UCS and MS. (2) The levels of organic substances, including
      total protein, glucose, triglycerides, cholesterol and various enzymes, were
      markedly lower in AF than in UCS and MS, especially for total protein, which was
      8- and 12.5-fold lower in AF than in UCS and MS, respectively. (3) The levels of
      tumor markers, including carcinoembryonic antigen, ferritin, cancer antigen 125
      and 199, and alpha-fetoprotein in AF displayed different dynamic changes compared
      to UCS and MS as gestation advanced. CONCLUSION: This study demonstrated that AF
      is not a result of simple filtration from the blood but an independent fluid. We
      speculate that proteins or peptides in the amniotic fluid modulate the process of
      fetus development since they possess potent bioactivity on cellular growth and
      proliferation. AF provides a pathway to transport these "regulators" to the fetus
      and thus plays a pivotal role in fetal development.

PMID- 19581144
TI  - Gastropericardial fistula and Candida albicans pericarditis: a rare complication
      of gastric adenocarcinoma treated with radiation and chemotherapy.
AB  - Gastropericardial fistula is generally associated with benign gastric diseases
      and is an uncommon complication of gastric adenocarcinoma. Pericarditis and
      cardiac tamponade are the ultimate outcome, with extremely high mortality rates.
      We report a 47-year-old man with gastric adenocarcinoma who had completed
      radiotherapy and was on scheduled chemotherapy, who presented with fever and
      chest pain. Gastric adenocarcinoma complicated with gastropericardial fistula and
      Candida albicans pericarditis were diagnosed and treated successfully with
      conservative management. Initial chest radiography and computed tomography (CT)
      revealed no evident pericardial air or fluid. However, follow-up panendoscopy 2
      weeks later revealed a malignant ulcer with a fistula opening over the lesser
      curvature of the high body of the stomach. Subsequent chest radiography and CT
      revealed pneumopericardium with fluid accumulation. Emergent CT-guided
      pericardial drainage was performed. The fluid was positive for Candida albicans.
      Total parenteral nutrition and antifungal therapy were administered. The patient
      refused surgical intervention and survived with medical management alone. This
      case demonstrates that first, panendoscopy may be safely performed in patients
      with gastropericardial fistula without significant risk of cardiac tamponade;
      second, although early diagnosis of gastropericardial fistula is generally
      important, delayed recognition may not lead to devastating outcomes even in the
      absence of surgical intervention.

PMID- 19581145
TI  - Dissection of arteria lusoria by transradial coronary catheterization: a rare
      complication evaluated by multidetector CT.
AB  - An aberrant right subclavian artery (arteria lusoria) arising from the descending
      thoracic aorta is an uncommon congenital variant that occurs in about 0.2-1.7% of
      the population. In such cases, the angular course of the arteria lusoria to the
      ascending aorta imposes difficulty in passing a guide wire to the ascending aorta
      during right transradial catheterization. Here, we present the first report of an
      iatrogenic dissection of arteria lusoria during transradial coronary angiography
      evaluated by multidetector computed tomography. Computed tomography is useful for
      assessing the severity and extension of the dissection to guide the clinical
      management of this complication.

PMID- 19581146
TI  - Brain metastasis of non-small cell lung cancer presenting as sensorineural
      hearing loss and vertigo.
AB  - We report a case of lung cancer with multiple metastases to the brain and
      internal auditory canal. A 59-year-old man complained about persistent and
      progressive vertigo for 3 weeks with rapidly developing left-sided hearing loss
      and tinnitus. Bilateral intact eardrums and unsteady gait were noted on physical
      examination. There was no nystagmus. Pure tone audiometry showed left-sided
      sensorineural hearing loss. Magnetic resonance imaging of the brain revealed
      multiple intracranial tumors, including of the left-side internal auditory canal,
      which were interpreted as seeding of metastatic malignancy. Computed tomographic
      and bronchoscopic biopsy identified an asymptomatic primary pulmonary
      adenocarcinoma in the right upper lobe of the lungs. This was a rare case of
      asymptomatic primary pulmonary adenocarcinoma with brain metastases presenting
      with sudden hearing loss and vertigo.

PMID- 19581147
TI  - Spontaneous suprachoroidal hemorrhage associated with age-related macular
      degeneration and anticoagulation therapy.
AB  - Suprachoroidal hemorrhage is a rare but dreadful event. We report the case of an
      86-year-old man with age-related macular degeneration (ARMD) in both eyes. He had
      been receiving anticoagulation therapy for several years for systemic disease. He
      presented with severe headache and intractable pain in his right eye. Vision was
      no light perception, and the intraocular pressure was 50 mmHg in the right eye
      despite maximal antiglaucoma medications. Slit-lamp and B-scan examination
      disclosed suprachoroidal hemorrhage in the right eye. Nine days later, he
      underwent choroidal drainage, which only relieved the symptoms for 1 day.
      Suprachoroidal hemorrhage recurred and evisceration was performed. This case
      illustrates how ARMD with anticoagulation therapy could cause spontaneous
      suprachoroidal hemorrhage. Therefore, anticoagulants should be meticulously
      prescribed with prothrombin time monitored regularly in ARMD patients.

PMID- 19581148
TI  - Malignant lymphoma in an atomic-bomb survivor.
AB  - Atomic bomb survivors outside of Japan are few and often hard to follow-up.
      Spinal malignant lymphoma among these survivors is rare in established studies
      from Japan or the United States. Here, we report an 81-year-old woman, who
      experienced the atomic bomb explosion in Nagasaki when she was 19 years old, who
      presented with papillary thyroid carcinoma when she was 70 years old. Both
      follicular lymphoma over the right elbow region and vertebral malignant lymphoma
      were found when she turned 81 years old. Bone scan did not show any increased
      uptake of isotope. However, thoracolumbar spine magnetic resonance imaging showed
      multiple infiltrative soft tissue masses involving vertebral bodies at the T10-11
      level. Computed tomography-guided biopsy further showed lymphocyte infiltration.
      Fortunately, the neurological deficit was improved after chemotherapy. The
      diagnosis of malignant lymphoma in atomic bomb survivors should be more careful
      and aggressive, even when their bone scan results show negative findings. In
      addition, the authors suggest that atomic bomb survivors should be followed-up
      carefully throughout their entire life.

PMID- 19581149
TI  - [Special situations in valvular heart diseases].

PMID- 19581150
TI  - [Functional mitral regurgitation].
AB  - Functional mitral regurgitation (FMR) is the mitral regurgitation that occurs due
      to myocardial disease in the presence of normal mitral valve leaflets. This
      scenario has the different characteristics than the organic mitral regurgitation.
      Functional mitral regurgitation is a disease of the ventricle and occurs by the
      deformation of the mitral valve leaflets. This morbid entity is frequent and has
      bad prognosis. Functional mitral regurgitation is the result of complex
      pathophysiologic process including left ventricular local and global remodeling,
      mitral annular and papillary muscle dysfunction, and left ventricular
      dysfunction. The dynamic behavior of FMR complicates the quantification of the
      regurgitation. Exercise stress echocardiography is of particular importance in
      the evaluation of the hemodynamic burden of FMR. Particular pathophysiological
      properties of the FMR necessitate different therapeutic approaches than the
      current ones for classical mitral regurgitation.

PMID- 19581151
TI  - [Valvular heart disease associated with coronary artery disease].
AB  - Nowadays, age-related degenerative etiologies have largely replaced the rheumatic
      ones and as a natural result of this etiologic change, coronary artery disease
      has become associated with valvular heart disease to a greater extent.
      Degenerative aortic valve disease has an important pathophysiological similarity
      to atherosclerosis and is the leader in this association. There is a general
      consensus that severely stenotic aortic valve should be replaced during bypass
      surgery for severe coronary artery disease. For moderate degree aortic stenosis,
      aortic valve replacement is usually performed during coronary bypass surgery.
      Ischemic mitral regurgitation has recently received great attention from both
      diagnostic and therapeutic points of view. Ischemic mitral regurgitation
      significantly alters the prognosis of the patient with coronary artery disease.
      Severe ischemic mitral regurgitation should be corrected during coronary bypass
      surgery and mitral valve repair should be preferred to valve replacement. For
      moderate degree ischemic mitral regurgitation, many authors prefer valve surgery
      with coronary bypass surgery. In this review, the main characteristics of
      patients with coronary artery disease accompanying valvular heart disease and the
      therapeutic options based on individual valve pathology are discussed.

PMID- 19581152
TI  - [Management of a patient with asymptomatic valvular heart disease].
AB  - Early diagnosis, treatment and follow-up are important in patients with
      asymptomatic valvular heart disease. Echocardiography is a valuable tool in this
      respect. In this review, the management of asymptomatic patients with valvular
      heart diseases is summarized according to the new guidelines.

PMID- 19581153
TI  - [Pregnancy and heart valve disease].
AB  - Rheumatic valve diseases are still a frequently encountered problem in developing
      countries. Valve disease has a high morbidity and mortality rate in pregnant
      patients. In this review the diagnosis, management and follow-up of the pregnant
      women with various valvular heart diseases are discussed.

PMID- 19581154
TI  - [Diagnosis and treatment of prosthetic valve dysfunction].
AB  - Prosthetic valve replacement replaces a heart disease with another one. There is
      no ideal prosthetic valve. All prostheses need to be followed by caution and
      treatment depends on the type of the prosthesis. Mechanical prostheses add
      anticoagulant drugs to patient's life and degeneration of bioprostheses requires
      reoperation. Prosthesis dysfunction includes a group of pathological processes
      like thrombosis, thromboemboli, valvular or paravalvular regurgitation, patient
      prosthesis mismatch, infective endocarditis and bioprosthesis degeneration.
      Correct diagnosis and treatment of these problems will decrease the mortality and
      morbidity due to prosthetic valve disease.

PMID- 19581155
TI  - [Management of the tricuspid valve regurgitation].
AB  - The tricuspid valve is the right-sided atrioventricular valve, and it is composed
      of three leaflets (i.e., anterior, posterior, and septal) attached to a fibrous
      annulus. The cause of tricuspid regurgitation (TR) is more often functional
      rather than due to a primary valve lesion. Functional TR is due to annular
      dilatation and secondary to mitral and aortic valvular diseases. Presence of the
      TR is associated with poor early and late prognosis. Patients with TR have the
      presenting symptoms of fatigue and weakness related to a reduction in cardiac
      output. Echocardiography is the best diagnostic method to evaluate TR and
      associated abnormalities. Tricuspid regurgitation is generally well tolerated.
      However, in the presence of pulmonary hypertension cardiac output declines and
      right heart failure worsens. The management depends on the underlying etiology
      and pathology of the TR. The surgical treatment technique is tricuspid valve
      annuloplasty rather than valve replacement.

PMID- 19581156
TI  - [Percutaneous approaches in valvular heart diseases].
AB  - Valvular heart diseases still continue to be an important health problem.
      Surgical replacement of cardiac valves keeps a widely used treatment method for
      the present. However, the efficiency of minimal invasive and percutaneous methods
      targeted to repair and replacement of the diseased valves has been searched for
      nowadays. The first clinical experiences and early stage outcomes on the
      applicability of these methods are encouraging. Nevertheless, it should be kept
      in mind that percutaneous valvular interventions are at their development stages.
      Long term confidence and efficiency studies of these treatment modalities are
      needed. The present review emphasizes the studies on percutaneous techniques
      initiated in the treatment of valvular heart diseases.

PMID- 19581158
TI  - [Frequencies of the Los Angeles and Duarte galactose-1-phosphate
      uridyltransferase variant alleles in the Hungarian population].
AB  - Classical galactosaemia is an autosomal recessively inherited disorder caused by
      deficient activity of the enzyme galactose-1-phosphate uridyltransferase (GALT),
      which can be detected by newborn screening. The p.N314D mutation defines two
      variant forms of the GALT enzyme, the Los Angeles and Duarte, depending on the
      presence of additional base changes. AIM: The aim of our study was to analyze a
      healthy Hungarian population for the frequencies of the Los Angeles and Duarte
      galactose-1-phosphate uridyltransferase variant alleles. METHODS: DNA samples
      from 100 subjects were analyzed by polymerase chain reaction, followed by
      digestion with restriction endonucleases. RESULTS: The frequencies of the
      p.N314D, the Los Angeles and the Duarte variants were 11.5%, 2.5% and 9%,
      respectively. CONCLUSIONS: The allele frequencies of the Los Angeles and Duarte
      variant alleles in the Hungarian population correlate well with the allele
      frequencies in other healthy Caucasian populations.

PMID- 19581160
TI  - [Whipple's disease. Do we think of it enough?].
AB  - Whipple's disease is a chronic, systemic, relapsing bacterial illness, which is
      always fatal without treatment, and means a diagnostic challenge for both
      clinicians and pathologists. It occurs in Caucasian, white, middle-aged men in 80
      % of the cases. CASE REPORT: The authors present three cases, and review the
      etiology, clinical features, presumed pathomechanism and the possibilities of
      treatment. CONCLUSION: Several immune-mechanisms have been discussed in the
      background of Whipple's disease, but their primary or secondary role is yet
      undetermined. First of all, this is a gastrointestinal disease; however,
      extraintestinal symptoms may be present many years before the final diagnosis.
      The histological hallmark for the diagnosis is the presence of numerous
      macrophages in the duodenal mucosa showing periodic acid-Schiff (PAS)-positive
      inclusions, and the polymerase chain reaction. The choice of antibiotics and the
      length of the treatment is empiric, but in most cases there is an immediate
      response to therapy. Relapses are common, especially the involvements of central
      nervous system.

PMID- 19581159
TI  - [Restenosis following endovascular interventions: clinical and experimental
      studies].
AB  - Restenosis following endovascular interventions is the main limitation of their
      long-term success. The incidence of restenosis varies according to the method
      (stenting, endarterectomy) and the treated vascular region, but the
      pathomechanism and risk factors are similar. The current article reviews of the
      author's previous studies in this field. In clinical studies, we compared the
      restenosis rate after carotid artery stenting and carotid endarterectomy. We also
      analyzed the complement activation profile after these interventions. In another
      study, we investigated the role of two polymorphisms of the estrogen receptor
      alpha in the occurrence of carotid restenosis after either carotid artery
      stenting or carotid endarterectomy. In an animal model of carotid endarterectomy,
      we studied the role of the nitrite-oxide-cyclic guanosine monophosphate signaling
      and the effect of the phosphodiesterase-5 inhibitor therapy in neointimal
      hyperplasia. Our results suggest that higher incidence of restenosis following
      carotid endarterectomy can be correlated with the more highly expressed
      complement activation after this type of carotid intervention. Polymorphisms in
      the estrogen receptor alpha gene could contribute to the restenosis formation,
      especially in women. Neointimal hyperplasia can be attenuated by increased cyclic
      guanosine monophosphate signaling.

PMID- 19581161
TI  - [Penrose's law: reality or fiction? Mental health system and the size of prison
      population - international overview].
AB  - According to the Penrose's law, outlined on the basis of a comparative study of
      European statistics, there is an inverse relationship between the number of
      psychiatric beds and prison population. Based on international data,
      interrelationship among prison, asylum, psychiatric disease and criminal action
      are investigated in the present study, paying particular attention to the event
      of deinstitutionalization. Prevalence of mental and addictive diseases as well as
      psychological disturbances in prison is characterized by epidemiological data. As
      proposed by Penrose, an inverse relationship between the number of psychiatric
      beds and prison population can be observed in Hungary, too. To get a deeper
      insight into the mainstream of the events, economic, sociological, philosophical,
      as well as therapeutic aspects initializing deinstitutionalization are
      highlighted in the course of analysis. On the basis of data, it can be assumed
      that members the same population are confined to both systems. The author arrives
      at the conclusion that deinstitutionalization has in fact led to trans
      institutionalization, because of, on one hand, the limited capacity of community
      treatment facilities; on the other hand, the community treatment itself cannot
      provide adequate treatment options to those suffering from severe, chronic mental
      diseases or comorbid states. In addition, the rate of financial support and the
      methods for prevention and treatment are insufficient to protect patients from
      the effects of revolving door.

PMID- 19581163
TI  - [Law in health].

PMID- 19581162
TI  - [Adalimumab in advanced and early rheumatoid arthritis].

PMID- 19581164
TI  - [Kissing and embracing, inherited ethological activity patterns and their
      depiction in fine arts].

PMID- 19581167
TI  - [Lajos Markusovszky Hospital - 90 years old].

PMID- 19581168
TI  - [The importance of multidetector computed tomography in the vascular imaging].
AB  - The introduction of multidetector CT and special post processing software has
      made an excellent image quality of vascular structures possible. AIM AND METHODS:
      The authors present the method and technique of CT angiography, added their own
      experience acquired on 700 patients in the last 3 years. Beside other vascular
      imaging methods the importance of CT angiography and its usefulness is
      demonstrated. CONCLUSIONS: CT angiography is a fast, non-invasive method, and
      either in itself or combined with other ones it is suitable for a definitive
      diagnosis.

PMID- 19581169
TI  - [The metabolic syndrome and the risks of unfavourable outcome of pregnancy].
AB  - The metabolic syndrome is defined by abdominal obesity, elevation of blood
      pressure, fasting glucose and triglycerides and low levels of high-density
      lipoprotein cholesterol. The metabolic syndrome may play an important role in the
      pathogenesis of unsuccessful pregnancy, by including a pro-inflammatory and
      prothrombotic state. Some authors have suggested that in case of metabolic
      syndrome the LMW heparin therapy given from the time of conception has a
      favourable effect. The aim of our study was to elucidate the association of the
      metabolic syndrome with the risk of unsuccessful pregnancy. DESIGN AND METHODS:
      During the study period 2005-2008 (4 years) we followed 5869 pregnancies.
      Retrospectively, 172 (2.9%) patients met the criteria of metabolic syndrome at
      the time of the first trimester. RESULTS: The rate of premature birth was 15.1%
      [26/172 in the metabolic syndrome group vs. 11.7%; OR: 1.52 (95% CI: 0.996-2.33)
      p=0.051], in control group. Within the affected group 32 pregnancies were
      complicated with intrauterine grow retardation (18.6%); versus 3.6%, in the
      unaffected group; OR: 6.38 (95% CI: 4.24-9.61 p<0.001). In 47 cases we observed
      preeclampsia during pregnancy [27.3%; vs. 4.7%; OR: 7.93 (95% CI: 5.54-11.33)
      p<0.001] in the control group. Among the patients affected by the metabolic
      syndrome 67 patients (38.2%) had more then one pregnancy complications during
      pregnancy, and only 47 cases (27.3%) were lacking adverse events during pregnancy
      and delivery [OR: 3.11 (2.27-4.26) p<0.001]. CONCLUSIONS: Our study demonstrated
      higher rate of complicated pregnancies in association with metabolic syndrome
      compared to the control group. In addition, we started a prospective study in
      2007, using LMWH therapy to prevent thromboplastic and atherosclerotic effects of
      the metabolic syndrome. The study is planned to be reported in 2010 to assess the
      effect of LMWH therapy on the outcome of pregnancies.

PMID- 19581170
TI  - [Manifestations of systemic mycoses and related infections in the central nervous
      system].
AB  - In daily practice mycotic infections of the CNS have become more and more
      frequent. The main causes are the wide-ranging use of corticosteroids,
      immunosuppressive, cytostatic drugs and antibiotics, the spreading of AIDS, the
      increasing number of surviving immature newborns. To illustrate the diagnostic
      difficulties, the authors report several cases. CASE REPORTS: 1. Multifocal
      hemorrhagic infarcts of the brain, caused by generalized aspergillosis in mantle
      cell malignant lymphoma. 2. Cerebral microabscesses, caused by systemic
      candidiasis in a premature infant. 3. Fatal actinomycosis, mimicking a space
      occupying tumour in the thigh and with an abscess in the brain, radiologically
      indicated as a metastasis. The cause of death was actinomycotic pneumonia. 4. A
      successfully treated and recovered patient with recurrent pneumonia and multiplex
      brain abscesses, caused by filamentous microorganism of a Nocardia species
      revealed by histological examination of the neurosurgical specimen. DISCUSSION
      AND CONCLUSIONS: We have to be aware for the development of the mycotic and
      related infections of endangered patients. Aspergillosis and candidiasis play the
      most significant role in the involvement of the central nervous system.
      Actinomycosis and nocardiosis are more sensitive to treatment, so their diagnosis
      is of life-saving importance. The therapeutic chances of high risk patients with
      aspergillosis and candidiasis will be definitively better, if the infection is
      recognized and appropriately treated before the involvement of the CNS.

PMID- 19581171
TI  - [Possible role of selected IGR and SLC22A4/SLC22A5 loci in development of
      inflammatory bowel diseases].
AB  - The IBD5 locus (MIM#606348) on chromosome 5q31 has been demonstrated to confer
      increased risk for inflammatory bowel disease. Controversial reports have been
      published about the significance of individual loci located in this region. Here
      we investigated the possible genetic association of inflammatory bowel diseases
      with C1672T of SLC22A4 and G-207C SLC22A5 alleles, and with IGR2096a_1
      (rs12521868) and IGR2198a_1 (rs11739135) susceptibility variants of the IBD5
      region located on chromosome 5q31. PATIENTS AND METHODS: Total of 440 patients,
      206 with Crohn's disease, 234 with ulcerative colitis, and 279 controls were
      studied by PCR-RFLP methods. RESULTS: Neither the C1672T, and G-207C alleles, nor
      the TC haplotype were found to confer risk for Crohn's disease or ulcerative
      colitis. By contrast, both of the minor allele frequencies of IGR2096a_1 T
      (48.1%) and IGR2198a_1 C (46.1%) were increased in Crohn's disease subjects as
      compared with the controls (38.5% and 38.4%, respectively; p<0.05). Using
      regression analysis adjusted to age and gender these alleles were found to confer
      risk for Crohn's disease (OR=1.694, 95% CI: 1.137-2.522; p=0.010 for T allele,
      OR=1.644, 95% CI=1.103-2.449; p=0.015 for C allele of IGRs). In UC no such
      associations were found. CONCLUSIONS: Our results revealed the susceptibility
      nature of the examined IGR minor alleles in Hungarians, which nation differs
      historically from the surrounding Caucasian populations in origin of the founders
      of the state.

PMID- 19581172
TI  - [Botulinum toxin therapy for focal dystonia].
AB  - Dystonia is a syndrome characterized by sustained muscle contraction. It is
      frequently causing twisting and repetitive movements, or leading to development
      abnormal postures. The management of the disease is usually consists of
      medication, surgical interventions, botulinum toxin injection, or other
      complementary methods. The authors have been using the botulinum toxin treatment
      since 1991. AIM: The goal of the study was to investigate the efficacy and safety
      of the botulinum toxin injection, in patients with focal dystonia and hemifacial
      spasm. METHODS: A total of 94 patients diagnosed with cervical dystonia (n=33),
      blepharospasm (n=32), or hemifacial spasm (n=29) were treated. The mean age of
      the patients was 62.4 years, and the mean duration of the therapy was 6.8 years.
      The medication took place with local injection of botulinum toxin type A. The
      efficacy of the treatment was assessed with Patient Global Impression scale. The
      authors also evaluated the side effects and complications of the therapy, as well
      as the causes of the treatment discontinuation. RESULTS: The botulinum toxin
      treatment was effective in 92% of the patients. It is a great importance that the
      therapy resulted significantly improvement in 56% of the patients. There was no
      significant difference neither among the types of the dystonia (cervical dystonia
      87%, blepharospasm 93%, and hemifacial spasm 96%), nor among the medications
      (Botox 92%, Dysport 92%) in point of efficacy. Temporary weakness occurred only
      at 6 patients. There was neither serious side effect, nor complication related to
      the treatment. CONCLUSIONS: The authors can conclude that the botulinum toxin
      injection is effective and safe therapy, in the patients with cervical dystonia,
      blepharospasm, and hemifacial spasm.

PMID- 19581173
TI  - [Healthcare law].

PMID- 19581176
TI  - [The significance of elastic staining in detecting vascular invasion in
      colorectal carcinoma].
AB  - Venous invasion (VI) is one of the most important prognostic factors in
      colorectal carcinomas (CRC). The interobserver variation of this feature varies
      between 10% and 89.5%, mainly due to the specimen processing and staining. VI was
      assessed using haematoxylin and eosin (H+E) alone in 611 cases and with elastic
      stain (orcein-haematoxylin) in 243 CRCs. The stage, the pattern of invasion and
      the presence of intramural and extramural VI were determined. VI was identified
      in 27.45% of the H+E stained sections and in 67.1% using elastic stain
      counterstained with haematoxylin. The incidence of VI proved stage dependent as
      it has been noted in 13% of Dukes A, 36% of Dukes B, 80% of Dukes C and in 83% of
      CRCs with distant metastasis. The pattern of invasion is strongly connected to
      the VI, accordingly, VI could be identified in 82% of CRCs with invasive and only
      in 44% with expansive margin. The use of elastic stain did not help in
      differentiation of extramural tumour deposits due to the damage of elastic
      membranes in the vascular walls and the presence of elastic fibres in the lymph
      node capsule. As a conclusion, the routine use of elastic stains in our practice
      doubled the identification of VI. The frequency of VI depends on the stage and
      pattern of invasion in CRCs. As it is more likely to occur in the advanced CRCs,
      the use of elastic stain is even more suggested in Dukes B carcinomas with
      invasive margin.

PMID- 19581175
TI  - [Chemotherapy of elderly patients with colorectal cancer].
AB  - Elderly patients will be the largest group of oncology patients in the future.
      Because of minimal participation of older patients in randomized clinical trials
      there is a lack of evidence-based data to make correct decisions with regard to
      chemotherapy and/or targeted therapy in this age group. Elderly patients have
      similar benefits from systemic therapies as younger counterparts, but many elders
      have substantial co-morbidities, which may limit the life expectancy and the
      effectiveness of systemic therapy. Close collaboration between oncologists and
      geriatrists will help make decisions on the management of elderly patients
      suffering from cancer.

PMID- 19581177
TI  - [New bibliometric indicators. Is this the end of the impact factor era?].
AB  - More and more bibliometric indicators emerge beside the impact factor, and a few
      of them are promising performance indicators. The aim of the study is to show
      briefly, but clearly the newest bibliometric measure numbers - like the recent
      enhancements of Journal Citation Report Web, Hirsch-index, Eigenfactor and
      SCImago Journal & Country Rank algorithms - focusing on the ranking of
      oncological journals, and to demonstrate the similarities and differences of the
      results with some examples. There are unified and well-structured web pages
      behind the newly appeared indicators, and some of the new numbers are presented
      in the well-known databases (Web of Science, Scopus) as scientific measures. The
      ranking of the compared oncological journals based on the different indicators
      show more similarities than differences, but more in-depth studies are required
      to find out how the results converge on any scientific area. There are some other
      methods, such as usage factor of the journals, beyond the indicators based on the
      citations. But the main point is that any ranking system should be a valid and
      correct representation of the scientific quality.

PMID- 19581178
TI  - [Diagnostic problems of ovarian mucinous borderline tumors].
AB  - About 15-20% of all ovarian epithelial neoplasms are of borderline type (or
      atypical proliferative or carcinoma of low malignant potential) and about 5-7%
      are mucinous type, which are the second most common type behind the serous
      borderline tumors. The borderline tumor is a serious diagnostic and treatment
      problem both for the pathologists and for clinicians. These tumors appeared to be
      intermediate in their histologic and prognostic features between the benign
      cystadenomas and clearly malignant carcinomas. The borderline tumors occur most
      commonly in childbearing age, and show an indolent course. Their prognosis is
      good, but they are resistant to the traditional chemotherapies. To diagnose the
      intraepithelial carcinoma, to detect the microinvasion and the expansive invasion
      in a mucinous borderline tumor, to differentiate from the metastasis of
      colorectal tumors may be very problematic in the majority of the cases. Eleven
      cases diagnosed as mucinous borderline ovarian tumor in our institute from 2000
      to 2008 were reviewed. Eight out of 11 were intestinal type while three were
      cervical (mullerian) type. In 5 cases our diagnosis was intraepithelial carcinoma
      and in 5 cases we found microinvasion. We discuss all of these problems according
      to the latest literature and our experience, mentioning the problems of the
      peritoneal and ovarian pseudomyxomas.

PMID- 19581179
TI  - [Panitumumab-treatment of metastatic colorectal cancer].
AB  - In the molecular target treatment strategy of metastatic colorectal cancer
      patients panitumumab represents a new class of drugs due to its fully human
      nature, and no need for premedication and loading dose. Panitumumab binds to
      epidermal growth factor receptor (EGFR) selectively. In registration pivotal
      studies the analysis of patient subgroups for KRAS status gives strong evidence
      for the important role of RAS oncogene: median progression-free survival was 16
      weeks on panitumumab arm in KRAS wild-type patients (8 weeks in best supportive
      care), while in KRAS mutant patients panitumumab showed no efficacy, however
      adverse events were more frequent and severe. According to SmPC, panitumumab is
      indicated as monotherapy for the treatment of patients with EGFR expressing
      metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure
      of fluoropyrimidine-, oxaliplatin- , and irinotecan-containing chemotherapy
      regimens. Adverse events are similar as with other EGFR inhibitors: skin symptoms
      (rash), lung infiltrates, diarrhoea, ion abnormalities of renal origin. The drug
      was formerly available via named patient reimbursement, and now is financed by
      diagnosis-related group (DRG) system.

PMID- 19581180
TI  - [The role of oncology nurses in treatment outcomes. What can we do for the
      patients' compliance treated with intravenous zoledronic acid?].
AB  - Patients with cancer and bone metastasis usually need to be treated with
      bisphosphonates to reduce or delay skeletal complications (pathologic fracture,
      hypercalcemia, surgery or radiotherapy). The nurses can provide important
      education to patients, support and encourage use of bisphosphonates throughout
      therapy. Literatures, training, congress reports provide useful information about
      bisphosphonate therapy, side effects, adverse events etc. However, patients need
      more information to support them during courses. To optimize the care, nurses can
      monitor pain scores, changes in mobility, adverse events, creating clearance
      levels. A useful tool for recording these parameters is a patients-diary. The
      nurse should fill out the diary at each patients visit and compare it to the
      baseline information before treatment. At the same time they can get some
      information from the patient's performance (adequate hydration, dental hygiene).
      Nurses play an important role in the care of patients during bisphosphonate
      therapy and in supporting patients to continue treatment to preserve their
      functional independence.

PMID- 19581181
TI  - [Post-transplantation malignant tumors and the challenges of immunosuppressive
      therapy in transplanted patients developing lymphoma. Mycophenolic acid as a
      possibility].
AB  - The increasing frequency of malignant tumors developing during chronic
      immunosuppression is an important determinant of the long-term survival of organ
      transplanted patients. This problem can be solved only if we are aware of the
      special characteristics concerning our patients. The incidence and frequency of
      tumors occurring in kidney transplant recipients differ from those of the
      Hungarian population. The increased tumor risk resulting from chronic renal
      failure, increasing age of prospective kidney recipients and, in addition, the
      increasing frequency of tumors diagnosed in the early post-transplantation period
      emphasize the importance of regular oncological screening of patients on the
      waiting list. Early diagnosis and treatment of tumors and precancerous conditions
      are equally important in transplanted patients as well, and the tumor risk could
      be decreased by applying low dose immunosuppression and the preferential usage of
      immunosuppressive drugs with an oncologically favorable effect. The prognosis of
      post-transplantation tumors is poor, as they respond poorly to therapy. Lymphomas
      are of great importance because of their frequency. Different immunosuppressive
      regimens represent varying degrees of risk in lymphoma development. This risk is
      lower in the case of mycophenolic acid. The composition of immunosuppression is a
      major factor in treatment; an oncologically ideal compound would prevent organ
      rejection and, at the same time, would not counteract oncological therapy. We
      have shown that mycophenolic acid inhibits the proliferation of human B-cell non
      Hodgkin lymphomas and induces apoptosis by activating the intrinsic pathway, both
      in vitro and in vivo. The favorable properties of mycophenolic acid suggest that
      it can provide the necessary immunoprotection for the transplanted organ and,
      given its anti-lymphoma effects, it may also prove useful in the therapy of
      lymphoma patients. It may also be helpful in the treatment of "traditional"
      lymphomas of the non-transplanted population, where the major cause of
      therapeutical failure is the development of apoptosis resistance. Mycophenolic
      acid, combined with other chemotherapeutical drugs, may enhance apoptosis in
      lymphoma cells. Our promising experimental results provide a basis for further,
      clinical studies.

PMID- 19581182
TI  - [Cytogenetic and hormonal changes in head and neck squamous cell cancer patients:
      potential biomarkers for functional approaches in surgical oncology].
AB  - Squamous cell cancer of the head and neck (SCCHN) is the third most common cause
      of death from cancer among Hungarian males. This cancer is caused in most of the
      cases by chronic toxic effects of the environment, especially by tobacco smoking
      and regular alcohol consumption. SCCHNs similar for the first sight, might have
      different clinical course, mainly because of their different responses to
      anticancer therapies. In this study, potential biomarkers were examined that were
      thought to develop as biologic responses to the known environmental toxicities,
      therefore, their testing is supposed to help answer the most important questions
      of clinical oncology: understanding tumor development, early detection of cancer
      and individually tailored therapy planning based on the biological nature of a
      particular cancer. Elevated rate of spontaneous chromosome aberrations proved to
      be a reliable marker of the SCCHN phenotype. However, increased mutagen
      sensitivity by the bleomycin-test, unlike in the US or in Western Europe, was not
      suitable to detect the individual cancer risk in this country, because of the
      high mutagen sensitivity of more than half of the healthy Hungarian population
      examined. In the light of the high cancer incidence and mortality statistics of
      Hungary, the frequency of elevated mutagen sensitivity even among healthy people
      is a meaningful finding, and requires further clarification. Our studies on the
      hormonal status of male SCCHN patients revealed some pathological changes in the
      sex steroid and pituitary hormone serum levels, which most probably accompanied
      chronic alcoholic liver disease. The elevated prolactin and decreased total and
      free testosterone levels predicted poor prognosis of the disease. The importance
      of the potential relationship between hormones and SCCHN is underscored by our
      further finding of functioning estrogen and progesterone receptors in SCCHN
      tissue of our patients.

PMID- 19581184
TI  - [Position statement of the Hungarian Radiotherapy and Oncology College on the
      insurance coverage of Vectibix (panitumumab)].

PMID- 19581185
TI  - [Position statement of the Hungarian Radiotherapy and Oncology College on the
      insurance coverage of Ratiograstim (biocompatible filgrastim)].

PMID- 19581187
TI  - [Abstracts from the 9th Congress of the Hungarian Radiotherapy Society, Pecs, May
      21-23, 2009].

PMID- 19581188
TI  - XII International Myeloma Workshop Education Book. February 26-March 1, 2009.
      Washington, DC, USA.

PMID- 19581196
TI  - Stress experienced by stroke survivors and spousal caregivers during the first
      year after discharge from inpatient rehabilitation.
AB  - PURPOSE: This study describes levels of stress in stroke survivors and spousal
      caregivers and identifies predictors of stress in couples during their first year
      at home. METHOD: The Perceived Stress Scale (PSS) was administered to 159 stroke
      survivors and caregivers at discharge and at 3, 6, 9, and 12 months. Other
      variables tested included stroke survivor function (FIM), health status,
      mutuality, stroke impact (SIS), caregiver coping (F-COPES), support (MOS Social
      Support Survey), and preparedness. Repeated measures analyses of PSS scores were
      conducted with linear mixed models for stroke survivors and caregivers. RESULTS:
      PSS scores for stroke survivors and caregivers were positively correlated
      (p<.01). Scores decreased significantly over the year, but caregivers had higher
      scores initially and decreased less. Stroke survivor function was a significant
      predictor of stress for both survivors and caregivers. Preparation was the most
      powerful predictor of stress in caregivers, whereas mutuality was the strongest
      predictor for stroke survivors. Good health, social support, and coping were
      associated with less stress. CONCLUSIONS: Stress is increased by poor function
      and mediated by internal and external buffers including health, the dyadic
      relationship, coping ability, and social support. More research using a dyadic
      research approach is needed to better understand stress within couples.

PMID- 19581198
TI  - The impact of a web-based caregiver intervention on the reasons stroke survivors
      use health care services during the first year post treatment.
AB  - PURPOSE: A Web-based education/support intervention for caregivers of stroke
      survivors was developed. A prospective, descriptive design was used to identify
      caregivers' reported reasons for stroke survivors' health care service use (i.e.,
      health care provider and emergency department visits, hospital readmissions)
      during the first year after initial treatment. METHOD: Caregivers were recruited
      in the Midwest and randomized into an experimental (Web users, n=36) or control
      (non-Web users, n=37) group. Telephone interviews were conducted with the
      caregivers every 2 weeks. Reported reasons were organized by group and time
      period in which the service occurred (i.e., Months 1-6 or 7-12; 1-year totals).
      Content analysis and descriptive statistics were used to analyze these data.
      RESULTS: Two themes emerged: wellness- and problem-oriented reasons for health
      care service use. Web users reported a large percentage of visits for
      rehabilitations reasons, which may have subsequently contributed to the
      musculoskeletal issues of this group. Laboratory work and testing was considered
      by both groups as a primary reason for provider visits. Non-Web users reported
      that medication adjustment was a common reason for provider visits. They also had
      more emergency department visits and hospital admissions for cardiology or
      pulmonology reasons. CONCLUSION: This study informs professionals about the care
      and needs of stroke survivors and provides direction for education and supportive
      interactions with caregivers and survivors.

PMID- 19581197
TI  - Stroke caregiver outcomes from the Telephone Assessment and Skill-Building Kit
      (TASK).
AB  - PURPOSE: Stroke caregivers often express the need for information about stroke
      and assistance with stroke-related care in the early discharge period. The
      Telephone Assessment and Skill-Building Kit (TASK) is an 8-week program that
      addresses caregiver needs. This study explored the efficacy of the TASK program
      in improving stroke caregiver outcomes. METHOD: Guided by a conceptual model, 6
      outcomes (optimism, task difficulty, threat appraisal, depressive symptoms, life
      changes, general health perceptions) were measured in 40 caregivers randomized to
      the TASK (n=21) or an attention control group (n=19). Data were analyzed using
      analysis of covariance (ANCOVA), controlling for baseline scores and minutes
      spent with the nurse. RESULTS: Significant increases in optimism at 4 weeks, 8
      weeks, and 12 weeks were found, with medium effect sizes for the TASK group
      relative to the control group (p<.05). Significant improvements in task
      difficulty at 4 weeks, and threat appraisal at both 8 weeks and 12 weeks were
      also found (p<.05). CONCLUSION: Caregivers receiving the TASK intervention
      improved in optimism, task difficulty, and threat appraisal. Further testing of
      an enhanced version of the TASK program is warranted, with attention directed
      toward more distal stroke caregiver outcomes.

PMID- 19581200
TI  - Using theory to develop an exercise intervention for patients post stroke.
AB  - Stroke remains a leading cause of disability for older adults. While is it well
      established in the literature that exercise programs can have significant
      benefit, many stroke survivors do not receive specific recommendations for
      exercise or lack the motivation to continue exercising following discharge from
      rehabilitation. This article describes an exercise intervention developed for
      subacute stroke survivors that utilizes the self-efficacy theory framework. The
      rationale for selection of this theoretical framework and specific examples of
      interventions linked to components of the model are provided. The article
      describes the motivational/educational program and the sequential follow-up
      designed to prepare stroke survivors to increase exercise behavior. Theoretical
      frameworks are useful tools for guiding and organizing research investigations
      from literature review through development and implementation of the intervention
      to interpretation of findings.

PMID- 19581199
TI  - Progressive adaptive physical activity in stroke improves balance, gait, and
      fitness: preliminary results.
AB  - PURPOSE: We conducted a non-controlled pilot intervention study in stroke
      survivors to examine the efficacy of low-intensity adaptive physical activity to
      increase balance, improve walking function, and increase cardiovascular fitness
      and to determine whether improvements were carried over into activity profiles in
      home and community. METHOD: Adaptive physical activity sessions were conducted 3
      times/week for 6 months. The main outcomes were Berg Balance Scale, Dynamic Gait
      Index, 6-Minute Walk Test, cardiovascular fitness (VO2 peak), Falls Efficacy
      Scale, and 5-day Step Activity Monitoring. RESULTS: Seven men and women with
      chronic ischemic stroke completed the 6-month intervention. The mean Berg Balance
      baseline score increased from 33.9+/-8.5 to 46+/-6.7 at 6 months (mean+/-SD;
      p=.006). Dynamic Gait Index increased from 13.7+/-3.0 to 19.0+/-3.5 (p=.01). Six
      minute walk distance increased from 840+/-110 feet to 935+/-101 feet (p=0.02).
      VO2 peak increased from 15.3+/-4.1 mL/kg/min to 17.5+/-4.7 mL/kg/min (p=.03).
      There were no significant changes in falls efficacy or free-living ambulatory
      activity. CONCLUSION: A structured adaptive physical activity produces
      improvements in balance, gait, fitness, and ambulatory performance but not in
      falls efficacy or free-living daily step activity. Randomized studies are needed
      to determine the cardiovascular health and functional benefits of structured
      group physical activity programs and to develop behavioral interventions that
      promote increased free-living physical activity patterns.

PMID- 19581201
TI  - Creating a supportive environment for living with stroke in rural areas: two low
      cost community-based interventions.
AB  - With the growing burden of chronic illness affecting aging populations, rural
      health systems are faced with unique challenges to support and promote health in
      their communities. The Yarmouth Stroke Project was a 5-year initiative aimed at
      improving health care services for stroke survivors in rural Nova Scotia, Canada.
      A needs assessment indicated a lack of support to self-manage stroke during
      community re-integration. The needs reported by stroke survivors and their
      caregivers included informational and emotional support. A logic model approach
      was used to frame program planning leading to the design of two low-cost
      interventions. The first, a Community Resource Guide, was developed to address
      informational needs and enable stroke survivors to access community-specific
      resources. The second intervention, designed to address the emotional support
      needs of stroke survivors and their caregivers, involved collection and
      publication of local narratives. The stories described the experiences of
      community members affected by stroke, offering practical knowledge and messages
      of hope. The resource guide and stories represent two low-cost strategies for
      supporting and promoting the health of people living with stroke in rural
      settings.

PMID- 19581202
TI  - Psychosocial predictors of quality of life in a sample of community-dwelling
      stroke survivors: a longitudinal study.
AB  - BACKGROUND: Stroke research and rehabilitation has traditionally focussed on the
      physical impact of a stroke, with less attention given to associated psychosocial
      factors. This study aimed to identify psychosocial predictors of health-related
      quality of life (HRQoL) in chronic stroke survivors and examine differences
      between nondepressed and depressed participants. METHOD: Participants were
      recruited primarily from six major metropolitan hospital databases. A total of
      135 first-ever stroke survivors aged 25-96 years who were 6 to 24 months post
      stroke and community-dwelling were studied longitudinally over 6 months. HRQoL
      and psychosocial factors (optimism, self-esteem, perceived control, depressive
      status, and social support) were measured at baseline, 10 weeks, and 6 months.
      RESULTS: Psychosocial factors were significantly associated with HRQoL at every
      time point, accounting for 33% to 53% of the variance after controlling for
      demographic and clinical characteristics. At least 26% of all participants
      reported clinically significant depressive symptoms throughout the study.
      Compared to nondepressed participants, depressed participants had significantly
      poorer scores for HRQoL, social support, optimism, self-esteem, perceived
      control, and physical functioning. There were improvements in participants'
      physical health, social participation, depressive status, and optimism over the
      course of the study. CONCLUSION: These findings highlight the important role that
      psychosocial factors play in chronic stroke survivors' HRQoL and have
      implications for stroke rehabilitation programs: rehabilitation that targets
      poststroke depression and psychosocial adjustment to stroke has the potential to
      improve HRQoL for chronic stroke survivors, independent of functional impairment.

PMID- 19581203
TI  - Estradiol and tamoxifen differently affects the inhibitory effects of vitamin A
      and their metabolites on the proliferation and expression of alpha2beta1
      integrins in MCF-7 breast cancer cells.
AB  - PURPOSE: Retinoids are well known inhibitors of estrogen-dependent breast cancer
      cell growth and differentiation. alpha2beta1 integrins are involved in the normal
      growth and differentiation of breast cells, they also take part in many
      pathological processes including malignancies. The aim of the study was to
      evaluate the effect of estradiol and tamoxifen on the inhibitory action of
      retinoids on the proliferation of MCF-7 breast cancer cells and alpha2beta1
      integrin expression. MATERIALS AND METHODS: Evaluation was based on [3H]thymidine
      incorporation and the proliferative activity of PCNA- and Ki 67-positive cells.
      Expression of alpha2beta1 was assessed through immunocytochemical analysis.
      RESULTS: Treatment of cancer cells with the examined compounds and tamoxifen (10
      microM) revealed that only 13-cis retinoic acid (13-cis RA) and all-trans
      retinoic acid (ATRA) (10(-5) M) decreased cells proliferation compared to the
      tamoxifen group (30.84%+/-3.32, p<0.01 and 31.05%+/-4.67, p<0.01, respectively).
      The lowest fraction of PCNA positive cells was also observed after the
      simultaneous addition ATRA (10(-5) M) and tamoxifen (10 microM) (30.75%+/-0.95,
      p<0.01, compared to the tamoxifen group). Our results showed that the decrease of
      alpha2beta1 integrin expression by 13-cis RA (10(-5) M, 49.6+/-3.25%) and ATRA
      (10-9 M, 15.0%+/-5.0) was augmented by tamoxifen and to a lesser extent by
      estradiol, particularly in the case of ATRA at 10(-7) or 10(-9) M. CONCLUSIONS:
      This data suggest that tamoxifen augments the inhibitory effect of retinoids on
      proliferation and alpha2beta1 integrin expression in MCF-7 cells.

PMID- 19581204
TI  - Capillary zone electrophoresis method for determination of bitter (alpha- and
      beta-) acids in hop (Humulus lupulus L.) cone extracts.
AB  - PURPOSE: Humulus lupulus (H. lupulus), more commonly known as hop, is a member of
      the Cannabaceae family with male and female flowers on separate plants. It is
      native in Europe including Lithuania, Asia and North America. Hop has been
      recognized as a medicinal plant for centuries, nevertheless different medicinal
      activities of hop are currently investigated and discovered. An important class
      of hop compounds is the hop acids, which are classified as alpha-acids and beta
      acids. Different varieties of hops vary in amount and composition of hop acids.
      METHODS: Simple capillary zone electrophoresis method has been optimized and
      applied for the analysis of hop acids in hop cone extracts. RESULTS: With this
      method the analysis takes ca. 10 min. Repeatability for migration times and peak
      areas expressed as relative standard deviation were up to 0.21% and 5.96%,
      respectively. CONCLUSIONS: Comparative results of capillary zone electrophoretic
      analysis of extracts of different hop varieties and conductometric titration, as
      a standard method for determination of alpha-acids, are presented. Both methods
      provide consistent results, however capillary zone electrophoresis is capable of
      separating co- form of humulones from other forms.

PMID- 19581206
TI  - D-amphetamine toxicity in freshly isolated rat hepatocytes: a possible role of
      CYP3A.
AB  - The aim of this study was to trace D-amphetamine toxicity in isolated rat
      hepatocytes and to elucidate a possible involvement of CYP3A in the mechanisms of
      its toxicity. To this end, male Wistar rats were treated with nifedipine (5 mg
      kg(-1) i.p., 5 days), a substrate and inducer of CYP3A. Hepatocytes isolated from
      nifedipine-treated and control rats were incubated with D-amphetamine at a
      concentration of 100 micromol L(-1), which was determined to be an average toxic
      concentration (TC50) for the compound. To evaluate the possible toxic effects of
      D-amphetamine on freshly isolated rat hepatocytes, we assessed the following
      parameters: cell viability, lactate dehydrogenase (LDH) activity, and glutathione
      (GSH).The results showed that nifedipine potentiated amphetamine cytotoxicity in
      vitro, as follows: cell viability dropped by 65% (p>0.001), GSH by 80% (p>0.001),
      and LDH activity increased by 190% (p>0.001). To clarify the role of nifedipine
      in amphetamine cytotoxicity, we used amiodarone, a substrate and an inhibitor of
      CYP3A. Pre-incubation of nifedipine-treated hepatocytes with amiodarone (14
      micromol L(-1)) significantly lowered amphetamine cytotoxicity. Our results
      confirmed the toxicity of D-amphetamine in isolated rat hepatocytes and the
      involvement of CYP3A in its metabolism and hepatotoxicity.

PMID- 19581205
TI  - Radioprotective effects of quercetin and ethanolic extract of propolis in gamma
      irradiated mice.
AB  - The aim of this study was to assess radioprotective effects of quercetin and the
      ethanolic extract of propolis (EEP) in CBA mice exposed to a single radiation
      dose 4 Gy (60Co). The mice were treated with 100 mg kg(-1) quercetin or EEP a day
      for three consecutive days either before (pre-treatment) or after gamma
      irradiation (therapy). Leukocyte count was determined in blood drawn from the
      tail vein, and DNA damage in leukocytes was assessed using the alkaline comet
      assay. Genotoxic effects of the test compounds were also evaluated in non
      irradiated mice. The levels of radioprotection provided by both test compounds
      were compared with those established in mice that were given chemical
      radioprotector S-(2-aminoethy1)isothiouronium bromide hydrobromide (AET). Mice
      that received pre-treatment were less sensitive to irradiation. Mice given the
      post-irradiation therapy showed a slight but not significant increase in total
      leukocyte count over irradiated negative control. Quercetin showed better
      protective properties than EEP in both pre-treatment and therapy, and activated a
      higher number of leukocytes in non-irradiated mice. The alkaline comet assay
      suggests that both natural compounds, especially when given as pre-treatment,
      protect against primary leukocyte DNA damage in mice. At tested concentrations,
      EEP and quercetin were not genotoxic to non-irradiated mice. AET, however, caused
      a slight but not significant increase in DNA damage. Although the results of this
      study show the radioprotective potential of the test compounds, further
      investigation is needed to clarify the underlying protection mechanisms.

PMID- 19581207
TI  - Rat serum carboxylesterase partly hydrolyses gamma-butyrobetaine esters.
AB  - Although described some time ago, gamma-butyrobetaine esters and related
      compounds have not gained much attention from researchers, and their
      physiological function remains obscure. Formerly we detected GBB-esterase
      enzymatic activity in rat blood serum using phenylated gamma-butyrobetaine as an
      artificial substrate of the enzyme and HPLC. The aim of the present work was to
      develop an assay that would enable spectrophotometric or colorimetric
      determination of the reaction products of GBB-esterase activity and to reveal
      individual proteins performing GBB-esterase activity in rat blood serum. For this
      purpose gamma-butyrobetaine 1-naphthyl ester was synthesised. Hydrolysis of this
      ester releases 1-naphthol, which increases the optical absorbance at 322 nm. We
      have shown that the enzymatic hydrolysis of GBB 1-naphthyl ester to 1-naphthol in
      rat blood serum is due to GBB-esterase activity. An attempt was done to purify
      the enzyme from rat blood serum. By combining DEAE Sepharose at pH 4.2 and
      affinity chromatography with procainamide we achieved a 68-fold enrichment of GBB
      esterase activity in our preparations. Separation of fraction proteins in 2D
      protein electrophoresis with following mass-spectrometry indicated that GBB
      esterase activity in rat blood serum is performed in part by carboxylesterase.

PMID- 19581208
TI  - Comparative effects of calcium channel blockers, autonomic nervous system
      blockers, and free radical scavengers on diazinon-induced hyposecretion of
      insulin from isolated islets of Langerhans in rats.
AB  - Hyperglycaemia has been observed with exposure to organophosphate insecticides.
      This study was designed to compare the effects of calcium channel blockers, alpha
      adrenergic, beta-adrenergic, and muscarinic receptor blockers, and of free
      radical scavengers on insulin secretion from diazinon-treated islets of
      Langerhans isolated from the pancreas of rats using standard collagenase
      digestion, separation by centrifugation, and hand-picking technique. The islets
      were then cultured in an incubator at 37 degrees C and 5 % CO2. In each
      experimental set 1 mL of 8 mmol L(-1) glucose plus 125 microg mL(-1) or 625
      microg mL(-1) of diazinon were added, except for the control group, which
      received 8 mmol L(-1) glucose alone. The cultures were then treated with one of
      the following: 30 micromol L(-1) atropine, 100 micromol L(-1) ACh + 10 micromol
      L(-1) neostigmine, 0.1 micromol L(-1) propranolol, 2 micromol L(-1) nifedipine,
      50 micromol L(-1) phenoxybenzamine, or 10 micromol L(-1) alphatocopherol. In all
      experiments, diazinon significantly reduced glucose-stimulated insulin secretion
      at both doses, showing no dose dependency, as the average inhibition for the
      lower dose was 62.20 % and for the higher dose 64.38 %. Acetylcholine and alpha
      tocopherol restored, whereas atropine potentiated diazinon-induced hyposecretion
      of insulin. Alpha-, beta- and calcium channel blockers did not change diazinon
      induced effects. These findings suggest that diazinon affects insulin secretion
      mainly by disturbing the balance between free radicals and antioxidants in the
      islets of Langerhans and by inducing toxic stress.

PMID- 19581210
TI  - Skin decontamination with mineral cationic carrier against sarin determined in
      vivo.
AB  - Our Institute's nuclear, biological, and chemical defense research team
      continuously investigates and develops preparations for skin decontamination
      against nerve agents. In this in vivo study, we evaluated skin decontamination
      efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier
      (MCC) with known ion exchange, absorption efficacy and bioactive potential. Mice
      were treated with increasing doses of sarin applied on their skin, and MCC was
      administered immediately after contamination. The results showed that
      decontamination with MCC could achieve therapeutic efficacy corresponding to 3 x
      LD(50) of percutaneous sarin and call for further research.

PMID- 19581209
TI  - Biological effects of Echinacea purpurea on human blood cells.
AB  - The aim of this study was to investigate radioprotective properties of Echinacea
      purpurea tablets in vivo. We analysed lymphocyte chromosome aberrations (CA),
      micronuclei (MN), apoptosis of leukocytes and haematological parameters in a
      group of radiation workers who were identified as carrying dicentric chromosomes
      in their lymphocytes. All radiation workers were taking two 275 mg Echinacea
      tablets b.i.d., according to a pharmacist's recommendation. All parameters were
      analysed before and after the two-week treatment. At the end of the treatment
      lymphocyte CA frequency dropped significantly, and the number of apoptotic cells
      increased. The inverse lymphocyte-to-granulocyte ratio at the beginning of the
      study changed to normal at its end. In conclusion, biological effects observed
      after administration of Echinacea purpurea preparation suggest that it may be
      beneficial for the prevention of adverse health effects in workers exposed to
      ionising radiation.

PMID- 19581211
TI  - In vitro genotoxicity of Settat town landfill leachate, Morocco.
AB  - With the increasing use of landfill sites, leachates produced by uncontrolled
      waste disposal have became a serious threat for the aquatic environment. The aim
      of this study was to evaluate the genotoxicity of leachate and of well water
      sampled close to the town of Settat in Morocco using the micronucleus test and
      proliferation kinetics of human peripheral blood lymphocytes in vitro. We also
      analysed a number of physical and chemical parameters, including pH, % O2,
      chemical oxygen demand (COD), HCO3(-), Ca2+, Mg2+, Cl(-), and conductivity. The
      analysis showed much higher levels of nearly all parameters than the Moroccan
      standard. Increased micronucleus frequencies were also found for both leachate
      and well water. Preliminary results indicate that both types of water are
      genotoxic and pose environmental and human health risk.

PMID- 19581212
TI  - Antinuclear antibody and rheumatoid factor in silica-exposed workers.
AB  - A lot of workers in industries such as foundry, stonecutting, and sandblasting
      are exposed to higher than permissible levels of crystalline silica. Various
      alterations in humoral immune function have been reported in silicosis patients
      and workers exposed to silica dust. The aim of this study was to measure
      antinuclear antibody (ANA) and rheumatoid factor (RF) levels in foundry workers
      exposed to silica and to compare them with a control group without such exposure.
      ANA and RF were measured in 78 exposed and 73 non-exposed workers, and standard
      statistical methods were used to compare them. The two groups did not
      significantly differ in age and smoking. Mean work duration of the exposed and
      non-exposed workers was (14.9+/-4.72) years and (12.41+/-6.3) years,
      respectively. Ten exposed workers had silicosis. ANA was negative in all workers
      in either group. Its mean titer did not differ significantly between the exposed
      and control workers [(0.39+/-0.15) IU mL(-1) vs. (0.36+/-0.17) IU mL(-1),
      respectively]. RF was positive in two workers of each group. Other studies have
      reported an increase in ANA and RF associated with exposure to silica dust and
      silicosis.In contrast, our study suggests that exposure to silica dust does not
      increase the level of ANA and RF in exposed workers.

PMID- 19581213
TI  - Interobserver variations in diagnosing asbestosis according to the ILO
      classification.
AB  - Inhalation of asbestos fibres leads to asbestosis of the pleura and the lung,
      with possible progression to lung cancer and malignant pleural or peritoneal
      mesothelioma. Asbestosis remains difficult to diagnose, especially in its early
      stages. The most important role in its diagnosis is that of chest radiographs.
      The aim of this cross-sectional study was to address interobserver variations in
      interpreting chest radiographs in asbestos workers, which remain to be an issue,
      despite improvements in the International Labour Office (ILO) classification
      system. In our ten-year study, we investigated 318 workers occupationally exposed
      to asbestos, and in 210 workers with diagnosed asbestos-related changes we
      compared interpretations of chest radiographs according to ILO by two independent
      radiologists. The apparent degree of interobserver variation in classifying lung
      fibrosis was 26.66% for the diameter of changes and 42.2% for the profusion of
      the changes. In cases with diffuse pleural thickening, the interobserver
      variation using ILO procedures was 34.93%. This investigation raises the issue of
      standardisation and objectivity of interpretation of asbestosis according to the
      ILO classification system. This study has revealed a significant disagreement in
      the estimated degree of pleural and parenchymal asbestos pulmonary disease. This
      is why we believe high-resolution computed tomography (HRCT) should also be used
      as a part of international classification.

PMID- 19581214
TI  - Prevalence of infection with Neisseria gonorrhoeae or Chlamydia trachomatis in
      acute mucopurulent cervicitis.
AB  - The aim of this study was to determine the incidence of N. gonorrhoae (NG) and/or
      C. trachomatis (CT) in acute mucopurulent cervicitis (MPC). The study included
      617 non-pregnant women with MPC, who had not been receiving any antimicrobial
      treatment. The average age of patients was 22.2 years. There were no
      statistically significant differences according to place of residence, education,
      and marital status. Samples for laboratory analysis were collected using a
      routine procedure; NG was identified using the cytochrome oxidase test and Gram
      staining. CT was isolated on McCoy cell culture and stained with Lugol solution.
      NG was isolated in three women (0.8%) and CT in 58 women (9.4%). Fifty-six of the
      CT-positive patients were nullipara and only two were unipara. All NG-positive
      patients were also nullipara. The mean number of sexual partners was 2.2 in all
      study subjects, 2.4 in CT-positive subjects, and 2.9 in NG-positive subjects.
      Vaginal discharge purity according to Schroder was significantly deteriorated in
      CT-positive patients (p=0.011). When asked about the use of contraceptives, as
      many as 32.7% patients answered that they did not use any protection, 39% women
      used the rhythm method and coitus interruptus, 20% were taking oral
      contraceptives, 6.1% used mechanical devices, and 1.9% used chemical protection.
      Previous acute and chronic pelvic inflammatory diseases correlated with MPC
      (p>0.01). Our statistical analysis suggests that chlamydial infection
      significantly reduces the purity of vaginal discharge, which is more pronounced
      in nulliparae. Pap smear was not specific enough to demonstrate chlamydial
      infection. In view of the MPC findings, the prevalence of CT and NG infection is
      low.

PMID- 19581216
TI  - Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor
      for drug response, toxicity, and cancer risk.
AB  - The polymorphic P450 (CYP) enzyme superfamily is the most important system
      involved in the biotransformation of many endogenous and exogenous substances
      including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms
      provides important genetic information that help to understand the effects of
      xenobiotics on human body. For drug metabolism, the most important polymorphisms
      are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which
      can result in therapeutic failure or severe adverse reactions. Genes coding for
      CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the
      biotransformation of chemicals, especially for the metabolic activation of pre
      carcinogens. There is evidence of association between gene polymorphism and
      cancer susceptibility. Pathways of carcinogen metabolism are complex, and are
      mediated by activities of multiple genes, while single genes have a limited
      impact on cancer risk. Multigenic approach in addition to environmental
      determinants in large sample studies is crucial for a reliable evaluation of any
      moderate gene effect. This article brings a review of current knowledge on the
      relations between the polymorphisms of some CYPs and drug activity/toxicity and
      cancer risk.

PMID- 19581215
TI  - The eye--a neglected organ in environmental and occupational medicine: an
      overview of known environmental and occupational non-traumatic effects on the
      eyes.
AB  - The objective of this study was to give an overview of the known literature data
      on the influence of environmental and occupational factors on the eye. Sixty-six
      articles were selected by searching Medline and PubMed databases using the
      following key words in different combinations: occupational and environmental
      factors, dry eye syndrome, cataract, retinal vascular changes. Most of the
      studies dealt with conditions on the eye surface and used eye discomfort syndrome
      and dry eye syndrome to outline the effects of air pollutants. Some reported
      increased frequency of lens opacities due to indoor fuel exposure, in particular
      biofuel, and negative effects of styrene exposure on colour vision.
      Investigations of retinal vascular changes and retinopathy after chronic exposure
      to carbon disulfide (CS2) and of retinal and choroidal haemodynamics after
      exposure to carbon monoxide (CO) found that CS2 caused an increase in retinal
      venous diameters and CO caused an increase in arterial and venous diameters,
      retinal blood flow velocity, and fundus pulsation amplitude. This article also
      discusses the influence of light exposure on retinal damage. It shows that very
      little information is available about the influence of environmental and
      occupational factors on the eye, and retina and retinal vessels in particular.

PMID- 19581217
TI  - [Analysis of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      in soil and sediment].
AB  - This review presents methods for the analysis of polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), called dioxins, in
      soil and sediment. These compounds are produced as by-products of different
      combustion processes, and because of their persistency and toxicity they present
      a threat for animal and human health. Due to their high organic matter content,
      soil and sediment can accumulate dioxins and have become important secondary
      emission sources. Determining dioxins in these samples is complex because dioxins
      are present in trace levels and have to be separated from interferences whereas
      other classes of organic contaminants are present in higher concentrations. After
      sampling, follows extraction of compounds with a suitable solvent, extract clean
      up from unwanted compounds, and qualitative and quantitative analysis. At the end
      of this review, we gave levels of PCDD/PCDFs found in soil and sediment samples.

PMID- 19581218
TI  - Hypersensitivity to the pollen of Olea europea in the Mediterranean area.

PMID- 19581219
TI  - Kinesthetic compensation for sensorimotor rearrangements.
AB  - The authors report a new sensorimotor phenomenon in which participants use hand
      sensed kinesthetic information to compensate for rotational sensorimotor
      rearrangements. This compensation benefits from conscious awareness and is
      related to hand posture. The technique can reduce control inefficiency with some
      misalignments by as much as 64%. The results support Y. Guiard's (1987)
      suggestion that in bimanual tasks one hand provides an operational frame of
      reference for the other hand as in a closed kinematic chain. Results with right
      handed participants show that the right and left hands are equally effective at
      providing such a cue. A constant-angular-targeting-error model, similar to that
      used for hand movements by H. Cunningham and I. Vardi (1990) and for walking by
      S. K. Rushton, J. M. Harris, M. R. Lloyd, and J. P. Wann (1998), is used to model
      the trajectories of targeting hand movements demonstrating the phenomenon. The
      model provides a natural parameter of the error.

PMID- 19581220
TI  - Update on the state of the science: sleep-wake disturbances in adult patients
      with cancer.
AB  - PURPOSE/OBJECTIVES: To update the state of the science on sleep-wake disturbances
      in adult patients with cancer, focusing on insomnia in the areas of prevalence,
      mechanisms and models, measurement, interventions, and implications for practice,
      health policy, education, and research. DATA SOURCES: Published articles, books,
      book chapters, MEDLINE, CINAHL, and PsycINFO computerized databases. DATA
      SYNTHESIS: Since the 2004 conference on Sleep-Wake Disturbances in People With
      Cancer and Their Caregivers, an increased focus has existed on the prevalence and
      distress experienced by patients with cancer with sleep-wake disturbances,
      particularly insomnia. Evidence suggests that altered physiology directly related
      to the cancer process may play a prominent role in disrupting sleep, circadian
      rhythms, and hypothalamic-pituitary-adrenal axis-regulated processes. Reliable
      and valid objective and subjective measurements for screening and assessing sleep
      wake disturbances are ready for use in clinical and research settings, and an
      increasing amount of intervention studies have reported sleep-wake outcomes in
      adult patients with cancer. CONCLUSIONS: Cognitive behavioral therapy
      interventions are likely to be effective, but effectiveness has not been
      established for complementary, education or information, or exercise
      interventions. IMPLICATIONS FOR NURSING: Multidisciplinary research teams should
      test the effectiveness of interventions to reduce sleep-wake disturbances in
      adult patients with cancer. Settings should create the infrastructure to initiate
      and sustain evidence-based oncology nursing practice, clinicians should educate
      the public about sleep, and public policies should promote adoption of healthy
      sleep patterns and early diagnosis and treatment of sleep disorders.

PMID- 19581221
TI  - Help seeking for cancer symptoms: a review of the literature.
AB  - PURPOSE/OBJECTIVES: To define help seeking and identify a theoretical framework
      to explain the help-seeking process of patients with self-discovered cancer
      symptoms. DATA SOURCES: Literature published in English from 1998-2008. DATA
      SYNTHESIS: Findings highlighted gender's role in help-seeking behavior. Delayed
      help seeking for cancer symptoms was common, with many associated influencing
      factors. To date, research on intentions to seek help has facilitated the
      development of health-promotion programs that target those who are likely to
      delay. CONCLUSIONS: Help seeking was defined as a response to health changes as
      well as a part of the broader process of health-seeking behavior. Reviewed
      frameworks and models provided knowledge and understanding about help-seeking
      behavior in various contexts. However, an all-encompassing framework explaining
      the entire process was not identified. IMPLICATIONS FOR NURSING: Nurses are in a
      unique position to promote prompt help seeking for patients with self-discovered
      cancer symptoms. Gaining clarity on the concept and identifying a theoretical
      framework may help nurses understand the complex nature of help seeking in
      patients with self-discovered cancer symptoms.

PMID- 19581222
TI  - Differences in physical, emotional, and social adjustment of intimate, family,
      and nonfamily patient-partner dyads based on a breast cancer intervention study.
AB  - PURPOSE/OBJECTIVES: To assess the degree to which postsurgical adjustment in
      patients with breast cancer and their partners depends on the nature of the
      patient-partner dyad relationship. DESIGN: Secondary data analysis from a
      randomized controlled trial. SETTING: Three cancer centers and one suburban
      community hospital in New York. SAMPLE: 205 patient-partner dyads (112 intimate
      partner, 58 family-member, and 35 nonfamily-member dyads). METHODS: Mann-Whitney
      nonparametric comparisons and chi-square tests were used to assess dyad types on
      continuous and categorical variables, and a mixed model for repeated measures
      compared postsurgical adjustment among dyad types. MAIN RESEARCH VARIABLES: Type
      of patient-partner dyads and physical, emotional, and social adjustment.
      FINDINGS: Patients in intimate-partner dyads were younger, had greater incomes,
      and discovered the lump by routine mammogram as compared to family- or nonfamily
      member dyads. No significant differences were observed in patients' physical or
      emotional adjustment. Patients with intimate partners had greater difficulty in
      their social and domestic environments. Partners in intimate-partner dyads had
      lower scores on psychological well-being, more problems in social and domestic
      adjustment, and less social support to promote social adjustment. CONCLUSIONS:
      Women with breast cancer experience successful physical and emotional adjustment
      whether they have intimate-partner, family-member, or nonfamily-member partners.
      Intimate partners are at greater risk for emotional and social adjustment issues.
      IMPLICATIONS FOR NURSING: When designing interventions, consideration must be
      given to the type of patient-partner dyad involved.

PMID- 19581223
TI  - The impact of dry versus moist heat on peripheral IV catheter insertion in a
      hematology-oncology outpatient population.
AB  - PURPOSE/OBJECTIVES: To determine whether dry versus moist heat application to the
      upper extremity improves IV insertion rates. DESIGN: Two-group, randomized,
      controlled clinical design. SETTING: An academic cancer infusion center in the
      western United States. SAMPLE: 136 hematologic outpatients with cancer or other
      malignancies. METHODS: Participants were randomly assigned to dry or moist heat
      with warmed towels wrapped around each patient's arm for seven minutes prior to
      IV insertion. Skin and room temperatures were monitored pre- and postwarming. Two
      experienced chemotherapy infusion nurses performed the venipunctures according to
      protocol. Outcomes were examined using variance analysis, with 34 patients for
      each combination of nurse and heat type. MAIN RESEARCH VARIABLES: Number of IV
      insertion attempts, time to achieve IV insertion postheating, patient anxiety
      levels pre- and postheating, and patient comfort. FINDINGS: Dry heat was 2.7
      times more likely than moist heat to result in successful IV insertion on the
      first attempt, had significantly lower insertion times, and was more comfortable.
      Heat type had no effect on patient anxiety. CONCLUSIONS: Dry heat application
      decreases the likelihood of multiple IV insertion attempts and procedure time and
      is comfortable, safe, and economical to use in an outpatient oncology setting.

PMID- 19581225
TI  - The effectiveness of nursing education as an intervention to decrease fatigue in
      Turkish patients receiving chemotherapy.
AB  - PURPOSE/OBJECTIVES: To determine whether a nurse-led educational intervention
      decreased the perception of fatigue in patients diagnosed with gastrointestinal
      (GI) cancers (colon, stomach, liver, rectum, pancreas) who were receiving
      chemotherapy for the first time. DESIGN: Quasi-experimental, descriptive.
      SETTING: Outpatient department in a large university hospital in Izmir, Turkey.
      SAMPLE: 35 patients receiving chemotherapy for GI cancers. METHODS: Baseline
      demographic data were collected using a personal information form developed by
      the researchers. Fatigue and quality of life (QOL) were then assessed using the
      Brief Fatigue Inventory, the Piper Fatigue Scale, and the European Organisation
      for Research and Treatment of Cancer Quality of Life (EORTC QLQ C-30) scale
      before their first cycle of chemotherapy, on the 10th day after (T1), and again
      10 days after the second cycle of chemotherapy (T2). Patients received an
      individual educational intervention at baseline, T1, and T2 based on the results
      of their fatigue assessment in accordance with the National Comprehensive Cancer
      Network (NCCN) cancer-related fatigue guidelines. Patients were given an
      educational booklet on fatigue prior to treatment and symptom specific booklets
      as required at T1 and T2. MAIN RESEARCH VARIABLES: Subjective reports of
      patients' fatigue and QOL. FINDINGS: Patients' mean fatigue scores showed a
      statistically significant decrease and their EORTC QLQC-30 scores were better at
      T1 and T2 compared with baseline. CONCLUSIONS: Nurse-led educational
      interventions have the potential to reduce fatigue in patients with GI cancer
      receiving chemotherapy for the first time. IMPLICATIONS FOR NURSING: The
      administration of chemotherapy should be preceded by a formal fatigue assessment
      and the provision of individually tailored educational interventions to reduce
      the severity of fatigue and improve QOL.

PMID- 19581224
TI  - The symptom cluster of fatigue, pain, anxiety, and depression and the effect on
      the quality of life of women receiving treatment for breast cancer: a multicenter
      study.
AB  - PURPOSE/OBJECTIVES: To examine the symptom cluster of fatigue, pain, anxiety, and
      depression and its effect on the quality of life (QOL) of women receiving
      chemotherapy or radiotherapy for breast cancer. DESIGN: Descriptive. SETTING:
      Oncology outpatient sections of four public hospitals in Hong Kong. SAMPLE: 215
      ethnic Chinese women who were midway through treatment for breast cancer.
      METHODS: Chinese versions of the Brief Fatigue Inventory, Hospital Anxiety and
      Depression Scale, Brief Pain Inventory, Functional Assessment of Chronic Illness
      Therapy for Breast Cancer, and Medical Outcomes Study Social Support Survey were
      used. Spearman rho correlation and structural equation modeling were used to
      examine the relationships among the study variables. MAIN RESEARCH VARIABLES:
      Breast cancer, fatigue, pain, anxiety, depression, and QOL. FINDINGS: Most
      participants reported mild-to-moderate levels of fatigue and pain. Twenty-one
      percent and 36% of patients might have had an anxiety or depression disorder,
      respectively. Significant correlations among the four symptoms supported the
      existence of the symptom cluster. The participants receiving chemotherapy had
      inadequate social support, experienced higher levels of symptoms, and were more
      likely to have a poorer QOL. CONCLUSIONS: The findings supported the existence of
      the symptom cluster that had detrimental effects on QOL. IMPLICATIONS FOR
      NURSING: This study shed light on a contemporary approach of grouping several
      related symptoms together. The findings enhance nurses' clinical sensitivity when
      identifying patients in high-risk groups and provide useful information for
      designing and prioritizing symptom-management strategies to meet patients' needs.

PMID- 19581226
TI  - Perspectives on music therapy in adult cancer care: a hermeneutic study.
AB  - PURPOSE/OBJECTIVES: To explore perspectives on music therapy as a nursing
      intervention in adult cancer care and to expand and integrate knowledge and
      understanding about music therapy as an adjunctive intervention in adult cancer
      nursing care. DATA SOURCES: Published nursing articles. DATA SYNTHESIS: Medical
      and nursing journals have reported on research related to music and its effect as
      a nursing intervention. However, this research often lacks a musical context
      (i.e., knowledge and understanding from a musical perspective). CONCLUSIONS:
      Music therapy is not a consistent concept. Perspectives on the meanings of music
      therapy vary according to knowledge and scientific orientation. The perspective
      may influence the character and methodology of the music therapy intervention as
      well as the understanding of its results. IMPLICATIONS FOR NURSING: To fully
      develop music therapy as an adjunct intervention in adult cancer care,
      interdisciplinary cooperation between nurses and music therapists should be
      supported on clinical and educational levels.

PMID- 19581227
TI  - It takes a village?

PMID- 19581228
TI  - Article highlights barriers to quality end-of-life care.

PMID- 19581229
TI  - A unique model of shared governance.

PMID- 19581230
TI  - Post-traumatic stress disorder related to the cancer experience.

PMID- 19581231
TI  - Exploring perceptions of cancer care delivery among older Mexican American
      adults.
AB  - PURPOSE/OBJECTIVES: To investigate older Mexican Americans' perceptions of cancer
      care delivery, specifically regarding perceived discrimination. RESEARCH
      APPROACH: Qualitative. SETTING: Senior centers and participants' homes.
      PARTICIPANTS: 5 older Mexican American cancer survivors. METHODOLOGIC APPROACH:
      The sample included five Spanish-speaking Mexican Americans with low incomes who
      were previously diagnosed with cancer. Ages ranged from 68-86 years (X = 76.4).
      Participants were recruited through several community-based agencies and
      resources. Interviews were conducted and recorded on audiotape in participants'
      homes or at a senior center. A demographic questionnaire and the Mini Mental
      State Exam were administered in English or Spanish. MAIN RESEARCH VARIABLES:
      Perceptions of healthcare delivery. FINDINGS: Three themes emerged from the
      interview data: (a) emotional responses to cancer diagnosis, (b) relationship
      with healthcare providers, and (c) use of spiritual resources in coping with
      cancer. Participants denied experiencing any discrimination in health care
      related to race, ethnicity, income, or language spoken. Perceptions of good and
      poor-quality health care are described. CONCLUSIONS: Participants were satisfied
      with the cancer care they received, with a few exceptions. The role of age and
      education level in perceived discrimination needs further exploration.
      INTERPRETATION: Replication of this study with larger, culturally diverse samples
      is needed to increase understanding of the role of perceived discrimination in
      cancer care and to develop culturally responsive, evidence-based healthcare
      interventions for patients and families coping with cancer.

PMID- 19581232
TI  - Centering prayer for women receiving chemotherapy for recurrent ovarian cancer: a
      pilot study.
AB  - PURPOSE/OBJECTIVES: To explore the feasibility of implementing centering prayer
      in chemotherapy treatment and assess its influence on mood, spiritual well-being,
      and quality of life in women with recurrent ovarian cancer. DESIGN: Descriptive
      pilot study. SETTING: Outpatient chemotherapy treatment suite in a large cancer
      center in the midwestern United States. SAMPLE: A convenience sample of 10 women
      receiving outpatient chemotherapy for recurrent ovarian cancer. METHODS: A
      centering prayer teacher led participants through three one-hour sessions over
      nine weeks. Data were collected prior to the first session, at the conclusion of
      the final session, and at three and six months after the final session. MAIN
      RESEARCH VARIABLES: Feasibility and influence of centering prayer on mood,
      spiritual well-being, and quality of life. FINDINGS: Most participants identified
      centering prayer as beneficial. Emotional well-being, anxiety, depression, and
      faith scores showed improvement. CONCLUSIONS: Centering prayer can potentially
      benefit women with recurrent ovarian cancer. Additional research is needed to
      assess its feasibility and effectiveness. IMPLICATIONS FOR NURSING: Nurses may
      promote or suggest centering prayer as a feasible intervention for the
      psychological and spiritual adjustment of patients with recurrent ovarian cancer.

PMID- 19581233
TI  - Cancer survivorship: history, quality-of-life issues, and the evolving
      multidisciplinary approach to implementation of cancer survivorship care plans.
AB  - PURPOSE/OBJECTIVES: To discuss the history of cancer survivorship, related
      quality-of-life issues, and cancer survivorship care plans (CSCPs). DATA SOURCES:
      CINAHL, PubMed, published articles, and Web sites. DATA SYNTHESIS: A cancer
      survivor is an individual who has been diagnosed with cancer, regardless of when
      that diagnosis was received, who is still living. Cancer survivorship is complex
      and involves many aspects of care. Major areas of concern for survivors are
      recurrence, secondary malignancies, and long-term treatment sequelae that affect
      quality of life. Four essential components of survivorship care are prevention,
      surveillance, intervention, and coordination. A CSCP should address the
      survivor's long-term care, such as type of cancer, treatments received, potential
      side effects, and recommendations for follow-up. It should include preventive
      practices, how to maintain health and well-being, information on legal
      protections regarding employment and health insurance, and psychosocial services
      in the community. CONCLUSIONS: Survivorship care for patients with cancer
      requires a multidisciplinary effort and team approach. Enhanced knowledge of long
      term complications of survivorship is needed for healthcare providers. Further
      research on evidence-based practice for cancer survivorship care also is
      necessary. IMPLICATIONS FOR NURSING: Nurses can review CSCPs with patients,
      instruct them when to seek treatment, promote recommended surveillance protocols,
      and encourage behaviors that lead to cancer prevention and promote well-being for
      cancer survivors.

PMID- 19581234
TI  - Fighting over food: patient and family understanding of cancer cachexia.
AB  - PURPOSE/OBJECTIVES: To investigate tensions over food that exist between patients
      with advanced cancer with cachexia and their families. RESEARCH APPROACH:
      Heideggerian phenomenologic inquiry using unstructured interviews. SETTING: A
      regional cancer center in the United Kingdom. PARTICIPANTS: 8 patients with
      advanced cancer living with cachexia and 8 family members. METHODOLOGIC APPROACH:
      Singular unstructured interviews were recorded digitally, transcribed verbatim,
      and analyzed using thematic and interpretative phenomenologic analysis. MAIN
      RESEARCH VARIABLES: Cachexia and advanced cancer. FINDINGS: A fine line existed
      between offering food to a patient and forcing a patient to eat; often, conflict
      arose as a result. Contributors to that conflict focused on reduced dietary
      intake by the patient and the reaction to food refusal by the family, which
      frequently led to patients eating to please. CONCLUSIONS: This study highlights
      the anxiety that surrounds eating and the distress it causes to patients and
      their families. This strain can escalate into arguments over food, causing
      negative repercussions for patients and their family members. INTERPRETATION:
      This is the first study to uncover tensions about eating as experienced by
      patients with advanced cancer and cachexia and their families. Nurses must
      consider this issue when designing and delivering effective care for this patient
      population.

PMID- 19581235
TI  - Oncology nurses' perceptions of obstacles and supportive behaviors at the end of
      life.
AB  - PURPOSE/OBJECTIVES: To determine the magnitude of selected obstacles and
      supportive behaviors in providing end-of-life (EOL) care to patients with cancer
      as perceived by oncology nurses. DESIGN: Cross-sectional survey. SETTING:
      National survey sample. SAMPLE: A geographically dispersed national random sample
      of 1,000 Oncology Nursing Society members who had cared for inpatient patients
      with cancer, could read English, and had experience in EOL care. METHODS:
      Eligible respondents received a 68-item questionnaire in the mail adapted from
      previous studies and were asked to rate the size of obstacles and supportive
      behavior items in caring for patients with cancer at the EOL. MAIN RESEARCH
      VARIABLES: EOL, oncology, barriers, supportive behaviors, oncology nurses, and
      survey research. FINDINGS: Returns after three mailings yielded 375 usable
      questionnaires from 907 eligible respondents for a return rate of 41%. The items
      with the highest perceived obstacle magnitude were (a) dealing with angry family
      members, (b) families not accepting what they are told about patients' poor
      prognosis, and (c) nurses being called away from dying patients to care for other
      patients. The three-highest scoring supportive behaviors were (a) allowing family
      members adequate time alone with patients after they died, (b) having social work
      or palliative care staff as part of the patient care team, and (c) having family
      members accept that patients are dying. CONCLUSIONS: EOL care can be improved by
      working to decrease the highest-rated barriers and by continuing to support the
      highest-rated supportive behaviors. IMPLICATIONS FOR NURSING: Oncology nurses are
      dedicated, experienced, and comfortable handling most issues in EOL care.
      Recommendations to support oncology nurses include strategies to interact
      effectively with angry, anxious, or overly optimistic family members as well as
      involving social work and palliative care staff on the oncology interdisciplinary
      team. In addition, the information regarding identified obstacles and supportive
      behaviors in oncology EOL care can be used to facilitate discussion and change
      within oncology interdisciplinary teams and improve EOL care for patients with
      cancer and their families.

PMID- 19581236
TI  - Factors that affect intention to avoid strenuous arm activity after breast cancer
      surgery.
AB  - PURPOSE/OBJECTIVES: To explore the factors that contribute to women's intention
      to avoid strenuous arm activity after breast cancer surgery. DESIGN: Cross
      sectional survey. SETTING: Three hospitals located in eastern Australia. SAMPLE:
      175 patients with breast cancer. METHODS: A survey, based on Protection
      Motivation Theory, was used to assess whether treatment variables, demographic
      variables, arm advice, fear, or coping attributes predicted women's intentions to
      avoid strenuous arm activity. MAIN RESEARCH VARIABLES: Intention to avoid
      strenuous arm activity, presence of arm or chest symptoms, receipt of arm care
      advice, and fear of lymphedema. FINDINGS: Seventy percent of participants
      reported an intention to avoid strenuous activity with their affected arm and
      reported more arm and chest symptoms than participants who did not avoid
      strenuous arm activity. Women who perceived that they were vulnerable to
      lymphedema and women who received advice about arm care were more likely to avoid
      strenuous arm activity. CONCLUSIONS: Fear of lymphedema and receipt of arm care
      advice motivated women's intention to avoid strenuous arm activity. IMPLICATIONS
      FOR NURSING: Information about lymphedema distributed to patients by healthcare
      professionals should be updated to reflect evidence and address the risk of
      developing lymphedema relevant to the patients' surgery.

PMID- 19581237
TI  - Older breast cancer survivors' symptom beliefs.
AB  - PURPOSE/OBJECTIVES: To use Leventhal's Common Sense Model (CSM) to describe older
      breast cancer survivors' symptom representations, symptom management strategies,
      and perceived barriers to symptom management. DESIGN: A secondary analysis was
      conducted using data from three pilot studies that tested a theory-based
      intervention to improve symptom management in older breast cancer survivors.
      SETTING: Advanced practice nurses conducted open-ended interviews with older
      breast cancer survivors either in their homes or via telephone. SAMPLE:
      Participants were recruited from the community, an oncology clinic, and a state
      tumor registry. The women (N = 61, X age = 69.5) were an average of 4.7 years
      after breast cancer diagnosis and reported an average of 17 symptoms. METHODS:
      Content analysis was conducted with field notes taken during baseline interviews.
      MAIN RESEARCH VARIABLES: Symptom representations, symptom management strategies,
      and perceived barriers to symptom management. FINDINGS: Women described their
      symptoms as chronic, incurable, and uncontrollable, with multiple causes (usually
      not aging) and numerous negative consequences. Women described an average of six
      symptom management strategies, most typically self-care. The most frequent
      barrier to symptom management was communicating with healthcare providers.
      CONCLUSIONS: The CSM is a useful framework for understanding the symptom beliefs
      of older breast cancer survivors. IMPLICATIONS FOR NURSING: Addressing women's
      beliefs and barriers may result in better communication with healthcare providers
      and more effective interventions for symptom management.

PMID- 19581239
TI  - Histopathological features of Capillaria hepatica infection in laboratory
      rabbits.
AB  - Capillaria hepatica is a nematode parasite of wild rodents and other mammals.
      Adult worms inhabit the liver. Recently, during the necropsy examination of a
      group of 160 rabbits from a commercial supplier, firm pale or cystic areas (1-5
      mm) were noted on the liver in thirteen animals. On further investigation, these
      animals were found to be infected with C. hepatica. The histopathological
      features of the infection in the rabbit are described for the first time and
      diagnostic features recorded. Lesions were identified predominantly in portal
      tracts consisting of dilated bile ducts with luminal debris, peribiliary
      inflammatory cell infiltrates, and fibrosis. Large granulomas (macrogranulomas)
      were evident in portal areas and involved the bile ducts. Macrogranulomas
      contained collections of characteristic C. hepatica eggs, macrophages,
      eosinophils, and lymphocytes. Small granulomas (microgranulomas), characterized
      by epithelioid macrophages surrounded by lymphocytes and eosinophils, were also
      identified. C. hepatica eggs were also observed in the lumina of the bile ducts
      and gall bladder. No adult C. hepatica worms were identified. Oocysts of Eimeria
      stiedae were also evident in the biliary epithelium in some animals. The unique
      characteristics of the C. hepatica life cycle are described, and the differential
      diagnosis of hepatic capillariasis is discussed.

PMID- 19581240
TI  - Chest x rays--who should report them acutely?

PMID- 19581241
TI  - Do radiologists still need to report chest x rays?
AB  - OBJECTIVE: Chest x rays (CXRs) are among the most difficult radiographs to
      interpret accurately. The aim of this study was to assess the ability of
      different grades and specialities of clinicians to evaluate a series of CXRs
      correctly. METHODS: 60 clinicians of different grades and from different
      specialities were randomly recruited to interpret 15 CXRs within 30 min.
      Radiographs included normal (n = 5) and abnormal images of common medical
      emergencies (n = 10). Non-parametric statistical tests examined for significant
      differences in the ability of different grades and specialities of doctors to
      interpret CXRs. RESULTS: Senior doctors (consultants and registrars, n = 32)
      attained significantly higher scores than junior doctors (senior house officers,
      foundation 1 and 2 doctors, n = 28, p = 0.001). Specialists (consultants and
      registrars in radiology and respiratory medicine, n = 7) achieved significantly
      higher scores than non-specialists (all other consultants and registrars, n = 25,
      p = 0.0002). In addition, senior radiologists (consultants and registrars)
      attained significantly higher scores than senior doctors from other specialities
      (p = 0.002). CONCLUSION: To improve patient care, we suggest that all chest x
      rays should be reviewed at an early stage during a patient's hospital admission
      by a senior clinician and reported by a radiologist at the earliest opportunity.
      We also suggest that structured teaching on CXR interpretation should be made
      available for newly qualified doctors, especially with the introduction of
      shortened training.

PMID- 19581242
TI  - Concurrent outbreaks of Chikungunya and Dengue fever in Kandy, Sri Lanka, 2006
      07: a comparative analysis of clinical and laboratory features.
AB  - OBJECTIVES: To compare the clinical and laboratory features of confirmed cases of
      Chikungunya and Dengue fever; to validate the clinical diagnosis based on
      serology. METHODS: Cases with a clinical diagnosis of Chikungunya and Dengue
      fever were recruited for seroconfirmation during a concurrent epidemic in 2006
      07, at the General Hospital, Peradeniya, Sri Lanka. RESULTS: Of 54 patients with
      fever, serology confirmed 21 with Chikungunya infection, 20 with Dengue
      infection, and three co-infections, with sensitivity of the clinical diagnosis of
      92% for Chikungunya fever and 95% for Dengue fever. The mean age of patients with
      Chikungunya fever was 45 years (range 21-74 years), and patients with Dengue
      fever was 30 years (range 15-63 years) (p = 0.005). Sixteen (70%) of Chikungunya
      fever patients were females, while 15 (71%) of those with Dengue fever were males
      (p = 0.007). Arthralgia was common to both groups (p = 0.155), while headache and
      a bleeding tendency were observed more in patients with Dengue fever. Twelve
      (57%) Chikungunya cases had acute arthritis compared with none in the Dengue
      group (p = 0.001), lasting mean 6 days (range 1-14 days). They developed chronic
      arthritic disability (range 1-6 months). Leucopenia was common to both
      Chikungunya and Dengue fever patients. However, thrombocytopenia was more
      pronounced in the Dengue patients (mean (SD) platelet count 75 (34)x10(9)/l) than
      in the Chikungunya patients (117 (70)x10(9)/l) (p = 0.001). In the Chikungunya
      group there was a positive correlation between duration of the illness and the
      platelet count (r = 0.181, p = 0.194), but the Dengue group showed a negative
      correlation (r = -0.309, p<0.001). CONCLUSION: Most of the clinical and
      laboratory features of patients with Chikungunya and Dengue fever are similar.
      Arthritis is the pathognomonic sign in patients with Chikungunya fever.

PMID- 19581243
TI  - Prescribing antibiotics for sore throat: adherence to guidelines in patients
      admitted to hospital.
AB  - AIM: We prospectively studied patients referred to secondary care with acute
      tonsillitis, peritonsillar cellulitis and quinsy (peritonsillar abscess) to see
      if recommended treatment guidelines were being followed and whether antibiotic
      resistance was contributing to admission. STUDY DESIGN: Prospective observational
      study in a university teaching hospital of 90 consecutive patients admitted to
      secondary care over an 18 month period with acute tonsillitis, peritonsillar
      cellulitis or quinsy were studied. The geographical distribution by postcode, pre
      admission history and treatment of each patient was recorded. The patients'
      general practitioners (GPs) were questioned about the patients' history, their
      use of antibiotics and prescribing guidelines and a patient questionnaire was
      completed. The result of hospital admission including throat swabs and blood
      cultures were recorded together with their treatment and outcome. RESULTS: 58% (n
      = 28) of patients who were prescribed antibiotics before admission received an
      inadequate dose or inappropriate antibiotic. Only 56% (n = 45) of GPs said they
      used guidelines for the treatment of acute sore throat. In 34 cases an organism
      was isolated, with 33 (97%) being sensitive to penicillin. No resistant organisms
      were isolated. Hospital doctors prescribed antibiotics contrary to guidelines in
      39% (n = 35) of cases. CONCLUSIONS: Antibiotic resistance was not demonstrated in
      this study. Adherence to guidelines for prescribing antibiotics in patients with
      features of group A beta-haemolytic streptococcal sore throat is poor.
      Information support may help to improve prescribing.

PMID- 19581244
TI  - Pan retinal haemorrhages in acute myeloid leukaemia.

PMID- 19581245
TI  - Ankylosing spondylitis in sub-Saharan Africa.
AB  - Ankylosing spondylitis (AS) represents a chronic inflammatory bone disease of the
      axial skeleton that manifests as chronic back pain and progressive stiffness of
      the spine. It characteristically affects young adults with a peak age of onset
      between 20-30 years. In contrast to Western Europe and North America, the disease
      is rare in Sub-Saharan Africa where the majority of the population is HLA-B27
      negative. Even in some African populations where HLA-B27 is prevalent (for
      example, in Gambia and Senegal, where 3-6% of the general population has HLA
      B27), the disease is also said to be rare. However, some other genetic markers
      may be involved in the causation of AS in the HLA-B27 negative population, and
      when it occurs in this subgroup of patients it has a similar manifestation with
      HLA-B27 negative white patients and these patients rarely develop anterior
      uveitis. The clinical presentation of the disease in Africa is generally milder;
      most affected individuals do not have a family history of AS, the patients are
      older at onset of the disease, and the majority of them lack extra-articular
      manifestations such as anterior uveitis compared with the situation in Western
      Europe and North America. In conclusion, AS in sub-Saharan Africa seems to
      represent a subgroup of the disease, which may open the window to a greater
      understanding of the pathophysiology of the condition.

PMID- 19581246
TI  - A review of novel biological tools used in screening for the early detection of
      lung cancer.
AB  - Lung cancer is the most common cancer worldwide and causes more deaths per year
      than any other cancer. It has a very poor 5-year survival rate of 8-16%, partly
      because of comorbidity preventing curative treatments but mainly because of the
      disease presenting with symptoms only when it is at an advanced and incurable
      stage. When lung cancer is detected earlier and is amenable to radical treatments
      such as potentially curative surgery and radical radiotherapy, 5-year survival
      rates are much higher (up to 67%). Therefore reliable detection of lung cancer at
      this earlier (usually asymptomatic) stage of disease should be an important way
      to improve outcomes. This review discusses the principles of screening with
      respect to lung cancer, concentrating mainly on the biological modalities used to
      detect it. The lack of impact achieved by early studies using sputum cytology (in
      conjunction with chest radiographs) is described, and then newer technology used
      to measure other biomarkers in sputum, serum, exhaled breath and bronchial mucosa
      to diagnose (early) lung cancer is detailed. Many techniques show promise, but
      debate continues about which population to screen and what is the most (cost)
      effective modality to use. Moreover, no single biomarker or combination of
      biomarkers in screening has yet been shown to reduce lung cancer mortality in
      large prospective randomised studies.

PMID- 19581247
TI  - Diagnosis and treatment of acquired coronary artery disease in adults.
AB  - Coronary artery disease evolves, often unnoticed, over decades, often culminating
      in myocardial infarction. Metabolic and behavioural risk factors affect the
      development and progression of atherosclerotic lesions. The diagnosis may be
      arrived at clinically but typically involves confirmatory and prognostic
      laboratory tests and imaging studies. Treatment measures are aimed at controlling
      symptoms and preventing disease progression. In patients with clinically stable
      disease, treatment centres upon preventing disease progression using lifestyle
      modification, medical therapy and revascularisation for patients in whom medical
      treatment failure may be imminently fatal. In patients with acute coronary
      syndrome, urgent treatment is required in order to arrest lesion progression.

PMID- 19581248
TI  - Management of the dialysis patient for the hospital physician.
AB  - As a relative shortage of organs limits transplantation rates in many countries,
      the number of patients on dialysis is increasing. Nephrologists in specialist
      centres supervise their dialysis, but increasingly in the context of acute
      medical emergencies, such patients present to district general hospitals.
      Experience in managing patients on dialysis varies among institutions. This
      review aims to provide a practical guide to aid general physicians involved in
      the delivery of hospital care, by outlining the principles of dialysis
      (haemodialysis and peritoneal dialysis) and examining relevant medical issues
      specific to dialysis patients.

PMID- 19581249
TI  - Bilateral serous macular detachments in Waldenstrom's macroglobulinaemia.

PMID- 19581250
TI  - Congenital and acquired conditions of the aortic root: multidetector computed
      tomography features.
AB  - The aortic root links the left ventricle and ascending aorta and functions as a
      support structure for the aortic valve. It can be affected by a variety of
      congenital and acquired conditions, some of which are potentially life
      threatening. Echocardiography and cardiac magnetic resonance imaging are
      established non-invasive imaging techniques for assessing the aortic root. Recent
      technological advances have allowed multidetector computed tomography to emerge
      as an alternative means of assessing this aortic segment. This pictorial essay
      reviews the anatomy of the aortic root and illustrates the salient computed
      tomography imaging features of a range of congenital and acquired conditions that
      may affect it.

PMID- 19581252
TI  - New and emerging tomographic imaging techniques in medical and industrial
      applications. Introduction.

PMID- 19581253
TI  - Microwave tomography: review of the progress towards clinical applications.
AB  - Microwave tomography (MWT) is an emerging biomedical imaging modality with great
      potential for non-invasive assessment of functional and pathological conditions
      of soft tissues. This paper presents a review of research results obtained by the
      author and his colleagues and focuses on various potential clinical applications
      of MWT. Most clinical applications of MWT imaging have complicated, nonlinear,
      high dielectric contrast inverse problems of three-dimensional diffraction
      tomography. There is a very high dielectric contrast between bones and fatty
      areas compared with soft tissues. In most cases, the contrast between soft-tissue
      abnormalities (the target imaging areas) is less pronounced than between bone
      (fat) and soft tissue. This additionally complicates the imaging problem. In
      spite of the difficulties mentioned, it has been demonstrated that MWT is
      applicable for extremities imaging, breast cancer detection, diagnostics of lung
      cancer, brain imaging and cardiac imaging.

PMID- 19581254
TI  - Quantitative photoacoustic tomography.
AB  - In this paper, several algorithms that allow for quantitative photoacoustic
      reconstruction of tissue optical, acoustic and physiological properties are
      described in a finite-element method based framework. These quantitative
      reconstruction algorithms are compared, and the merits and limitations associated
      with these methods are discussed. In addition, a multispectral approach is
      presented for concurrent reconstructions of multiple parameters including
      deoxyhaemoglobin, oxyhaemoglobin and water concentrations as well as acoustic
      speed. Simulation and in vivo experiments are used to demonstrate the
      effectiveness of the reconstruction algorithms presented.

PMID- 19581255
TI  - Diffuse optical imaging.
AB  - Diffuse optical imaging is a medical imaging technique that is beginning to move
      from the laboratory to the hospital. It is a natural extension of near-infrared
      spectroscopy (NIRS), which is now used in certain niche applications clinically
      and particularly for physiological and psychological research. Optical imaging
      uses sophisticated image reconstruction techniques to generate images from
      multiple NIRS measurements. The two main clinical applications--functional brain
      imaging and imaging for breast cancer--are reviewed in some detail, followed by a
      discussion of other issues such as imaging small animals and multimodality
      imaging. We aim to review the state of the art of optical imaging.

PMID- 19581257
TI  - Unscented Kalman filter approach to tracking a moving interfacial boundary in
      sedimentation processes using three-dimensional electrical impedance tomography.
AB  - The monitoring of solid-fluid suspensions under the influence of gravity is
      widely used in industrial processes. By considering sedimentation layers with
      different electrical properties, non-invasive methods such as electrical
      impedance tomography (EIT) can be used to estimate the settling curves and
      velocities. In recent EIT studies, the problem of estimating the locations of
      phase interfaces and phase conductivities has been treated as a nonlinear state
      estimation problem and the extended Kalman filter (EKF) has been successfully
      applied. However, the EKF is based on a Gaussian assumption and requires a
      linearized measurement model. The linearization (or derivation of the Jacobian)
      is possible when there are no discontinuities in the system. Furthermore, having
      a complex phase interface representation makes derivation of the Jacobian a
      tedious task. Therefore, in this paper, we explore the unscented Kalman filter
      (UKF) as an alternative approach for estimating phase interfaces and
      conductivities in sedimentation processes. The UKF uses a nonlinear measurement
      model and is therefore more accurate. In order to justify the proposed approach,
      extensive numerical experiments have been performed and a comparative analysis
      with the EKF is provided.

PMID- 19581256
TI  - Numerical modelling and image reconstruction in diffuse optical tomography.
AB  - The development of diffuse optical tomography as a functional imaging modality
      has relied largely on the use of model-based image reconstruction. The recovery
      of optical parameters from boundary measurements of light propagation within
      tissue is inherently a difficult one, because the problem is nonlinear, ill-posed
      and ill-conditioned. Additionally, although the measured near-infrared signals of
      light transmission through tissue provide high imaging contrast, the
      reconstructed images suffer from poor spatial resolution due to the diffuse
      propagation of light in biological tissue. The application of model-based image
      reconstruction is reviewed in this paper, together with a numerical modelling
      approach to light propagation in tissue as well as generalized image
      reconstruction using boundary data. A comprehensive review and details of the
      basis for using spatial and structural prior information are also discussed,
      whereby the use of spectral and dual-modality systems can improve contrast and
      spatial resolution.

PMID- 19581258
TI  - Visualization of multidimensional and multimodal tomographic medical imaging
      data, a case study.
AB  - Multidimensional tomographic datasets contain physical properties defined over
      four-dimensional (e.g. spatial-temporal, spatial-spectral), five-dimensional
      (e.g. spatial-temporal-spectral) or even higher-dimensional domains. Multimodal
      tomographic datasets contain physical properties obtained with different imaging
      modalities. In medicine, four-dimensional data are widely used, five-dimensional
      data are emerging, and multimodal data are being used more often every day.
      Visualization is vital for medical diagnosis and surgical planning to interpret
      the information included in imaging data. Visualization of multidimensional and
      multimodal tomographic imaging data is still a challenging task. As a case study,
      our work focuses on the visualization of five-dimensional (spatial-temporal
      spectral) brain electrical impedance tomography (EIT) data. In this paper, a task
      based subset definition scheme is proposed: a task model named Cubic Task
      Explorer (CTE) is derived to support the visualization task exploration for
      medical imaging data, and a structured method for visualization system
      development called Task-based Multi-Dimensional Visualization (TMDV) is proposed.
      A prototype system named EIT5DVis is developed using the CTE model and TMDV
      method to visualize five-dimensional brain EIT data.

PMID- 19581259
TI  - Role of pulse oximetry in examining newborns for congenital heart disease: a
      scientific statement from the AHA and AAP.
AB  - BACKGROUND: The purpose of this statement is to address the state of evidence on
      the routine use of pulse oximetry in newborns to detect critical congenital heart
      disease (CCHD). METHODS AND RESULTS: A writing group appointed by the American
      Heart Association and the American Academy of Pediatrics reviewed the available
      literature addressing current detection methods for CCHD, burden of missed and/or
      delayed diagnosis of CCHD, rationale of oximetry screening, and clinical studies
      of oximetry in otherwise asymptomatic newborns. MEDLINE database searches from
      1966 to 2008 were done for English-language papers using the following search
      terms: congenital heart disease, pulse oximetry, physical examination, murmur,
      echocardiography, fetal echocardiography, and newborn screening. The reference
      lists of identified papers were also searched. Published abstracts from major
      pediatric scientific meetings in 2006 to 2008 were also reviewed. The American
      Heart Association classification of recommendations and levels of evidence for
      practice guidelines were used. In an analysis of pooled studies of oximetry
      assessment performed after 24 hours of life, the estimated sensitivity for
      detecting CCHD was 69.6%, and the positive predictive value was 47.0%; however,
      sensitivity varied dramatically among studies from 0% to 100%. False-positive
      screens that required further evaluation occurred in only 0.035% of infants
      screened after 24 hours. CONCLUSIONS: Currently, CCHD is not detected in some
      newborns until after their hospital discharge, which results in significant
      morbidity and occasional mortality. Furthermore, routine pulse oximetry performed
      on asymptomatic newborns after 24 hours of life, but before hospital discharge,
      may detect CCHD. Routine pulse oximetry performed after 24 hours in hospitals
      that have on-site pediatric cardiovascular services incurs very low cost and risk
      of harm. Future studies in larger populations and across a broad range of newborn
      delivery systems are needed to determine whether this practice should become
      standard of care in the routine assessment of the neonate.

PMID- 19581260
TI  - Decline and change in seasonality of US rotavirus activity after the introduction
      of rotavirus vaccine.
AB  - BACKGROUND: In 2006, routine immunization of US infants against rotavirus was
      initiated. We assessed national, regional, and local trends in rotavirus testing
      and detection before and after vaccine introduction. METHODS: We examined data
      for July 2000 through June 2008 from a national network of approximately 70 US
      laboratories to compare geographical and temporal aspects of rotavirus season
      timing and peak activity. To assess trends in rotavirus testing and detection, we
      restricted the analyses to 33 laboratories that reported for >or=26 weeks per
      season from 2000 to 2008. RESULTS: Nationally, the onset and peak of the 2007
      2008 rotavirus season were delayed 15 and 8 weeks, respectively, compared with
      prevaccine seasons from 2000-2006. Delays were observed in each region. The 2007
      2008 rotavirus season lasted 14 weeks compared with a median of 26 weeks during
      the prevaccine era. Of 33 laboratories, 32 reported fewer positive results and a
      lower proportion of positive test results in 2007-2008 compared with the median
      in 2000-2006, with a 67% decline in the number and a 69% decline in the
      proportion of rotavirus-positive test results. The proportion of positive test
      results in 2007-2008 compared with the median in 2000-2006 declined >50% in 79%
      of the laboratories and >75% in 39% of the laboratories. CONCLUSIONS: The 2007
      2008 US rotavirus season seems substantially delayed, shorter, and diminished in
      magnitude compared with seasons before vaccine implementation. The extent of
      change seems greater than expected on the basis of estimated vaccine coverage,
      suggesting indirect benefits to unvaccinated individuals. Monitoring in future
      seasons is needed to confirm these trends.

PMID- 19581261
TI  - Association of family history of autoimmune diseases and autism spectrum
      disorders.
AB  - OBJECTIVES: Recent studies suggest that familial autoimmunity plays a part in the
      pathogenesis of ASDs. In this study we investigated the association between
      family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform
      confirmatory analyses based on results from previous studies, as well as various
      explorative analyses. METHODS: The study cohort consisted of all of the children
      born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted
      of both inpatient and outpatient diagnoses reported to the Danish National
      Psychiatric Registry. Information on ADs in parents and siblings of the cohort
      members was obtained from the Danish National Hospital Register. The incidence
      rate ratio of autism was estimated by using log-linear Poisson regression.
      RESULTS: A total of 3325 children were diagnosed with ASDs, of which 1089 had an
      infantile autism diagnosis. Increased risk of ASDs was observed for children with
      a maternal history of rheumatoid arthritis and celiac disease. Also, increased
      risk of infantile autism was observed for children with a family history of type
      1 diabetes. CONCLUSIONS: Associations regarding family history of type 1 diabetes
      and infantile autism and maternal history of rheumatoid arthritis and ASDs were
      confirmed from previous studies. A significant association between maternal
      history of celiac disease and ASDs was observed for the first time. The observed
      associations between familial autoimmunity and ASDs/infantile autism are probably
      attributable to a combination of a common genetic background and a possible
      prenatal antibody exposure or alteration in fetal environment during pregnancy.

PMID- 19581262
TI  - Attending physician work hours: ethical considerations and the last doctor
      standing.
AB  - Based at least in part on concerns for patient safety and evidence that long
      shifts are associated with an increased risk of physician error, residents' and
      fellows' work hours have been strictly limited for the past several years. Little
      attention has been paid, however, to excessive attending physician shift
      duration, although there seems to be no reason to assume that this common
      practice poses any less risk to patients. Potential justifications for allowing
      attending physicians to work without hourly limits include physician autonomy,
      workforce shortages in certain communities or subspecialties, continuity of care,
      and financial considerations. None of these clearly justify the apparent
      increased risk to patients, with the exception in some settings of workforce
      shortage. In many hospital settings, the practice of allowing attending
      physicians to work with no limit on shift duration could pose an unnecessary risk
      to patients.

PMID- 19581263
TI  - 13C-sucrose breath test: novel use of a noninvasive biomarker of environmental
      gut health.
AB  - OBJECTIVE: Environmental enteropathy syndrome may compromise growth and
      predispose to infectious diseases in children in the developing world, including
      Australian Aboriginal children from remote communities of the Northern Territory.
      In this study, we described the use of a biomarker (13)C-sucrose breath test
      (SBT) to measure enterocyte sucrase activity as a marker of small intestinal
      villus integrity and function. METHODS: This was a hospital-based prospective
      case-control study of Aboriginal and non-Aboriginal children with and without
      acute diarrheal disease. Using the SBT, we compared 36 Aboriginal case subjects
      admitted to a hospital (18 diarrheal and 18 nondiarrheal disease), with 7 healthy
      non-Aboriginal control subjects. Intestinal permeability using the
      lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test was performed
      simultaneously with the SBT. The SBT results are expressed as a cumulative
      percentage of the dose recovered at 90 minutes. RESULTS: Aboriginal children with
      acute diarrheal disease have a significantly decreased absorptive capacity, as
      determined by the SBT, with a mean of 1.9% compared with either Aboriginal
      children without diarrhea (4.1%) or non-Aboriginal (6.1%) control subjects. The
      mean L/R ratio in the diarrhea group was 31.8 compared with 11.4 in Aboriginal
      children without diarrhea. There was a significant inverse correlation between
      the SBT and the L/R ratio. CONCLUSIONS: The SBT was able to discriminate among
      Aboriginal children with diarrhea, asymptomatic Aboriginal children with an
      underlying environmental enteropathy, and healthy non-Aboriginal controls. This
      test provides a noninvasive, easy-to-use, integrated marker of the absorptive
      capacity and integrity of the small intestine and could be a valuable tool in
      evaluating the efficacy of interventions aimed at improving gut health.

PMID- 19581265
TI  - Fragile X syndrome.

PMID- 19581264
TI  - Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in
      neonates of <28 weeks' gestation.
AB  - BACKGROUND: Transiently low levels of thyroid hormones occur in approximately 50%
      of neonates born 24-28 weeks' gestation and are associated with higher rates of
      cerebral palsy and cognitive impairment. Raising hormone levels shows promise for
      improving neurodevelopmental outcome. OBJECTIVE: To identify whether any of 4
      thyroid hormone supplementation regimens could raise T(4) and FT(4) without
      suppressing TSH (biochemical euthyroidism). METHODS: Eligible subjects had
      gestational ages between 24 07 and 2767 weeks and were randomized <24 hours of
      birth to one of six study arms (n = 20-27 per arm): placebo (vehicle: 5%
      dextrose), potassium iodide (30 microg/kg/d) and continuous or bolus daily
      infusions of either 4 or 8 microg/kg/d of T(4) for 42 days. T(4) was accompanied
      by 1 microg/kg/d T(3) during the first 14 postnatal days and infused with 1 mg/mL
      albumin to prevent adherence to plastic tubing. RESULTS: FT(4) was elevated in
      the first 7 days in all hormone-treated subjects; however, only the continuous 8
      microg/kg/d treatment arm showed a significant elevation in all treatment epochs
      (P < .002 versus all other groups). TT(4) remained elevated in the first 7 days
      in all hormone-treated subjects (P < .05 versus placebo or iodine arms). After 14
      days, both 8 microg/kg/d arms as well as the continuous 4 microg/kg/d arm
      produced a sustained elevation of the mean and median TT(4), >7 microg/dL (90
      nM/L; P < .002 versus placebo). The least suppression of THS was achieved in the
      4 microg/kg/d T(4) continuous infusion arm. Although not pre-hypothesized, the
      duration of mechanical ventilation was significantly lower in the continuous 4
      microg/kg/d T(4) arm and in the 8 microg/kg/d T(4) bolus arm (P < .05 versus
      remaining arms). ROP was significantly lower in the combined 4 thyroid hormone
      treatment arms than in the combined placebo and iodine arms (P < .04). NEC was
      higher in the combined 8 microg/kg/d arms (P < .05 versus other arms).
      CONCLUSIONS: Elevation of TT(4) with only modest suppression of TSH was
      associated with trends suggesting clinical benefits using a continuous supplement
      of low-dose thyroid hormone (4 microg/kg/d) for 42 days. Future trials will be
      needed to assess the long-term neurodevelopmental effects of such
      supplementation.

PMID- 19581266
TI  - Quantitative analysis of CPR quality during in-hospital resuscitation of older
      children and adolescents.
AB  - OBJECTIVE: Few data exist on pediatric cardiopulmonary resuscitation (CPR)
      quality. This study is the first to evaluate actual in-hospital pediatric CPR. We
      hypothesized that with bedside CPR training and corrective feedback, CPR quality
      can approach American Heart Association (AHA) targets. PATIENTS AND METHODS:
      Using CPR recording/feedback defibrillators, quality of CPR was assessed for
      patients >or=8 years of age who suffered a cardiac arrest in the PICU or
      emergency department (ED). Before and during the study, a bedside CPR training
      program was initiated. RESULTS: Between October 2006 and February 2008, twenty
      events in 18 patients met inclusion criteria and resulted in 36749 evaluable
      chest compressions (CCs) during 392.3 minutes of arrest. CCs were shallow (<38 mm
      or <1.5 in) in 27.2% (9998 of 36749), with excessive residual leaning force
      (>or=2500 g) in 23.4% (8611 of 36749). Segmental analysis of the first 5 minutes
      of the events demonstrated that shallow CCs and excessive residual leaning force
      were less prevalent during the first 5 minutes. AHA targets were not achieved for
      CC rate in 62 (43.1%) of 144 segments, CC depth in 52 (36.1%) of 144 segments,
      and residual leaning force in 53 (36.8%) of 144 segments. CONCLUSIONS: This
      prospective, observational study demonstrates feasibility of monitoring in
      hospital pediatric CPR. Even with bedside CPR retraining and corrective
      audiovisual feedback, CPR quality frequently did not meet AHA targets.
      Importantly, no flow fraction target of 10% was achieved. Future studies should
      investigate novel educational methods and targeted feedback technologies.

PMID- 19581267
TI  - Gender differences in research grant applications for pediatric residents.
AB  - OBJECTIVE: Recent studies have reported gender differences in research grant
      applications and funding outcomes for medical school faculty. Our goal was to
      determine whether similar patterns exist at the resident level and, if so, to
      explore possible explanations. METHODS: We conducted a retrospective review of
      all applications to an internal, mentored research grant fund at a large academic
      pediatric residency program from 2003 to 2008. We determined whether gender
      differences existed for application characteristics and outcomes and defined
      significant predictors of success. RESULTS: During the 5-year period, the fund
      supported 42 (66%) of 64 applications. Among all applicants, men were more likely
      than women to hold an advanced research degree. Men requested more money than
      women and obtained more favorable application scores. Funding success rates were
      not statistically different between male and female applicants. Among funded
      applicants, men received higher awards than women, although the percentage of
      requests funded was the same. In a multiple regression analysis, advanced degree
      was the significant independent predictor of successful funding outcome.
      Controlling for advanced degree attenuated the association between gender and
      timing of application, type of project, dollars requested, and dollars awarded;
      however, even after controlling for advanced degree, women had inferior grant
      scores compared with men. CONCLUSIONS: Gender differences existed in research
      grant applications and funding among pediatric residents that mirrored faculty
      patterns. Among residents, these differences were explained in part by the
      correlation of male gender with holding an advanced research degree.

PMID- 19581268
TI  - What determines nutritional recovery in malnourished children after correction of
      congenital heart defects?
AB  - BACKGROUND: Malnutrition is common in children with congenital heart disease
      (CHD), especially in developing countries. OBJECTIVE: To examine the impact of
      corrective intervention on the nutritional status of children with CHD and
      identify factors associated with suboptimal recovery. METHODS: Consecutive
      patients with CHD in a tertiary center in South India were evaluated for
      nutritional status before and 2 years after corrective intervention.
      Anthropometry was performed at presentation and every 6 months for 2 years, and z
      scores were compared. Malnutrition was defined as a weight-for-age, height-for
      age, and weight/height z score <-2. Determinants of malnutrition were entered
      into a multivariate logistic regression analysis model. RESULTS: Of 476 patients
      undergoing corrective intervention (surgical: 344; catheter-based: 132) z scores
      of less than -2 for weight for age, height for age, and weight/height were
      recorded in 59%, 26.3%, and 55.9% of patients, respectively, at presentation. On
      follow-up (425 patients [92.5% of survivors; 20.63 +/- 13.1 months of age]), z
      scores for weight for age and weight/height improved significantly from the
      baseline (weight: -1.42 +/- 1.03 vs -2.19 +/- 1.16; P < .001; weight/height: 
      1.15 +/- 1.25 vs -2.09 +/- 1.3; P < .001). Height-for-age z scores were not
      significantly different. Malnutrition persisted in 116 (27.3%) patients on follow
      up and was associated with a birth weight of <or=2.5 kg, nutritional status at
      presentation, and height of parents and not with type of cardiac lesion, dietary
      intake, or socioeconomic factors. CONCLUSIONS: This study from South India
      demonstrates severe malnutrition in over half of the patients with CHD and is not
      always reversed by corrective surgery or intervention. Persistent malnutrition
      after corrective intervention is predicted by nutritional status at presentation,
      birth weight, and parental anthropometry.

PMID- 19581270
TI  - Managing heparin anticoagulation in patients with prosthetic cardiac valves:
      balancing the risk.

PMID- 19581269
TI  - No change in the age of diagnosis for fragile x syndrome: findings from a
      national parent survey.
AB  - OBJECTIVE: To determine recent trends in the diagnosis of children with fragile X
      syndrome (FXS) and identify factors associated with the timing of diagnosis.
      METHODS: More than 1000 families of children with FXS participated in a national
      survey. Of these, 249 had their first child (213 boys, 36 girls) diagnosed
      between 2001 and 2007 and did not know about FXS in their family before
      diagnosis. These parents answered questions about the average age of first
      concerns, developmental delays, early intervention, and the FXS diagnosis. They
      also provided other information about their child and family, reported who made
      the diagnosis, and described ramifications for other children and extended family
      members. RESULTS: The average age of FXS diagnosis of boys remained relatively
      stable across the 7-year period at approximately 35 to 37 months. The 36 girls
      with full mutation were given the diagnosis at an average age of 41.6 months. A
      trend was noted in earlier diagnosis of developmental delay for boys in more
      recent years. Approximately 25% of the families of male children had a second
      child with the full mutation before the diagnosis was given to the first child;
      14 (39%) of the 36 families of female children had a second child with the full
      mutation before the diagnosis. CONCLUSIONS: Despite patient advocacy,
      professional recommendations regarding prompt referral for genetic testing, and
      increased exposure to information about FXS in the pediatric literature, no
      changes were detected in the age of diagnosis of FXS during the time period
      studied. Earlier identification in the absence of systematic screening will
      likely continue to be a challenge.

PMID- 19581271
TI  - Delays in angiography may cost lives.

PMID- 19581272
TI  - Multislice computed tomography coronary angiography for risk stratification in
      patients with an intermediate pretest likelihood.
AB  - OBJECTIVES: To assess whether multislice computed tomography coronary angiography
      (MSCTA) may be useful for risk stratification of patients with suspected coronary
      artery disease (CAD) at intermediate pretest likelihood according to Diamond and
      Forrester. DESIGN AND PATIENTS: MSCTA images were evaluated for the presence of
      significant CAD in 316 patients with suspected CAD (60% male, average (SD) age 57
      (11) years) and an intermediate pretest likelihood according to Diamond and
      Forrester. Patients were followed up to determine the occurrence of an event.
      MAIN OUTCOME MEASURES: A combined end point of all-cause mortality, non-fatal
      infarction and unstable angina requiring revascularisation. RESULTS: Significant
      CAD was seen in 89 patients (28%), whereas normal MSCTA or non-significant CAD
      was seen in the remaining 227 (72%) patients. During follow-up (median 621 days
      (25-75th centile 408-835) an event occurred in 13 patients (4.8%). The annualised
      event rate was 0.8% in patients with normal MSCT, 2.2% in patients with non
      significant CAD and 6.5% in patients with significant CAD. Moreover, MSCTA
      remained a significant predictor (p<0.05) of events after multivariate correction
      (hazard ratio = 3.460 (95% CI 1.142 to 10.480). CONCLUSIONS: The results suggest
      that in patients with an intermediate pretest likelihood, MSCTA is highly
      effective in re-stratifying patients into either a low or high post-test risk
      group. These results further emphasise the usefulness of non-invasive imaging
      with MSCTA in this patient population.

PMID- 19581273
TI  - First head-to-head comparison of effective radiation dose from low-dose 64-slice
      CT with prospective ECG-triggering versus invasive coronary angiography.
AB  - BACKGROUND: Reduction of radiation burden of multidetector computed tomography
      coronary angiography (CTCA) has remained an important task. OBJECTIVE: To compare
      effective radiation dose of low-dose 64-slice CTCA using prospective ECG
      triggering versus diagnostic invasive coronary angiography (CA). METHODS: 42
      patients referred for elective invasive CA owing to suspected coronary artery
      disease (CAD) were prospectively enrolled to undergo a low-dose CTCA without
      calcium scoring within the same day before CA. Dose-area product of diagnostic
      invasive CA and dose-length product of CTCA were measured, converted into
      effective radiation dose and compared using Mann-Whitney U tests. In addition,
      accuracy of CTCA to detect CAD (coronary artery narrowing > or =50%) was assessed
      using invasive CA as standard of reference. On an intention-to-diagnose basis all
      non-evaluative vessels were included in the analysis and censored as positive.
      RESULTS: The estimated mean effective radiation dose was 8.5 (4.4) mSv (range 1.4
      20.5 mSv) for diagnostic invasive CA, and 2.1 (0.7) mSv (range 1.0-3.3 mSv) for
      CTCA (p<0.001). 19 patients (42.9%) had no CAD by invasive CA. 40 (95.2%)
      patients have been correctly classified as having CAD (23/23) or no CAD (17/19).
      Over 97% (551/567) of segments were evaluable. Vessel-based analysis revealed
      sensitivity, specificity, positive and negative predictive value of 94.2% (CI
      0.8% to 1.0%), 94.8% (CI 09% to 1.0%), 89.0% (CI 0.8% to 1.0%), 97.4% (CI 09% to
      1.0%) and an accuracy of 94.6%. CONCLUSIONS: Low dose CTCA allows evaluation of
      CAD with high accuracy, but delivers a significantly less effective radiation
      dose to patients compared to diagnostic invasive CA.

PMID- 19581275
TI  - Association between a polymorphism in the human programmed death-1 (PD-1) gene
      and cytomegalovirus infection after kidney transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is the most frequent infectious
      disease following organ transplantation. Strategies to prevent this infection
      remain a matter for debate, and discovering genetic risk factors might assist in
      adapting preventive strategies. By inhibiting IFNgamma production, programmed
      death 1 (PD-1) has a crucial role in anti-CMV immune response. A single
      nucleotide polymorphism (SNP) within intron 4 of the gene (rs11568821), called PD
      1.3, has recently been reported to be clinically relevant in several immune
      disorders. However, its association with CMV infection has never been reported.
      METHODS: In this study, the risk of CMV infection according to PD-1.3 genotype
      was investigated in 469 kidney graft recipients transplanted between 1995 and
      2005. RESULTS: It was found that the A allele was associated with the risk of CMV
      infection in seropositive patients who did not receive CMV prophylaxis (OR=2.60,
      p=0.006). Multivariate analysis including other risk factors for CMV infection
      showed that this allele was independently associated with CMV infection (OR=2.54;
      p=0.010). Interestingly, combined analysis of PD-1.3 with the IL12B 3'UTR SNPs
      (previously shown to be associated with CMV infection) revealed that patients
      with the PD-1.3 A allele had a much higher risk of CMV infection compared to
      those having neither risk allele (OR=3.76; p=0.0003). CONCLUSION: This study
      identified a new genetic risk factor for CMV infection after kidney
      transplantation and suggests that an adjustment of CMV prophylaxis based on
      genetic markers would merit further investigation.

PMID- 19581274
TI  - OPA1 increases the risk of normal but not high tension glaucoma.
AB  - BACKGROUND: Primary open angle glaucoma is a progressive optic neuropathy
      characterised by the selective loss of retinal ganglion cells, pathological optic
      disc cupping and visual field defects. The OPA1 gene encodes an inner
      mitochondrial membrane protein crucial for normal mitochondrial function, and
      pathogenic mutations cause autosomal dominant optic atrophy by specifically
      targeting retinal ganglion cells. This raises the distinct possibility that more
      subtle genetic variations in OPA1 could alter the risk of developing glaucoma.
      METHODS: 137 patients with primary open angle glaucoma (67 patients with high
      tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75
      controls from the North East of England were studied. Three single-nucleotide
      polymorphisms in intron 8 (IVS8+4c-->t and IVS8+32t-->c) and exon 4 (c.473A-->G)
      of the OPA1 gene were genotyped in the study group. In addition, the entire OPA1
      coding region was sequenced in 24 individuals with the CT/TT compound genotype
      using standard BigDye chemistries. RESULTS: There was no difference in either
      allele or genotype frequency for the IVS8+32t-->c single-nucleotide polymorphisms
      between patients and controls, but there was a significant association between
      the T allele at IVS8+4c-->t and the risk of developing NTG (OR=2.04, 95% CI=1.10
      to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a
      strong association between the CT/TT compound genotype at IVS8+4 and IVS8+32 with
      NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001). CONCLUSIONS: The CT/TT compound
      genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but
      not HTG.

PMID- 19581276
TI  - Smoking uptake and prevalence in Ghana.
AB  - BACKGROUND: Developing countries are at high risk of epidemic increases in
      tobacco smoking, but the extent of this problem is not clearly defined because
      few collect detailed smoking data. We have surveyed tobacco smoking in the
      Ashanti region of Ghana, a rapidly developing African country with a long
      established tobacco industry. METHODS: We took a random sample of 30 regional
      census enumeration areas, each comprising about 100 households, and a systematic
      sample of 20 households from each. These were visited, a complete listing of
      residents obtained and questionnaire interviews on current and past smoking, age
      at smoking uptake, sources of cigarettes and other variables carried out in all
      consenting residents aged 14 or over. RESULTS: Of 7096 eligible individuals
      resident in the sampled households, 6258 (88%; median age 31 (range 14-105)
      years; 64% female) participated. The prevalence of self-reported current smoking
      (weighted for gender differences in response) was 3.8% (males 8.9%, females 0.3%)
      and of ever smoking 9.7% (males 22.0%, females 1.2%). Smoking was more common in
      older people, those of Traditionalist belief, those of low educational level, the
      unemployed and the less affluent. Smokers were more likely to drink alcohol and
      to have friends who smoke. About 10% of cigarettes were smuggled brands. About a
      third of smokers were highly or very highly dependent. CONCLUSIONS: Despite rapid
      economic growth and a sustained tobacco industry presence, smoking prevalence in
      Ghana is low, particularly among younger people. This suggests that progression
      of an epidemic increase in smoking has to date been avoided.

PMID- 19581277
TI  - Chronic bronchitis before age 50 years predicts incident airflow limitation and
      mortality risk.
AB  - BACKGROUND: Previous studies on the relationship of chronic bronchitis to
      incident airflow limitation and all-cause mortality have provided conflicting
      results, with positive findings reported mainly by studies that included
      populations of young adults. This study sought to determine whether having
      chronic cough and sputum production in the absence of airflow limitation is
      associated with onset of airflow limitation, all-cause mortality and serum levels
      of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age
      influences these relationships. METHODS: 1412 participants in the long-term
      Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972
      1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1
      s/forced vital capacity) > or = 70% and no asthma were identified. Chronic
      bronchitis was defined as cough and phlegm production on most days for > or = 3
      months in two or more consecutive years. Incidence of airflow limitation was
      defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP
      levels were measured in cryopreserved samples from the enrolment survey. RESULTS:
      After adjusting for covariates, chronic bronchitis at enrolment significantly
      increased the risk for incident airflow limitation and all-cause mortality among
      subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8;
      respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to
      1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with
      increased IL-8 and CRP serum levels only among subjects <50 years old.
      CONCLUSIONS: Among adults <50 years old, chronic bronchitis unaccompanied by
      airflow limitation may represent an early marker of susceptibility to the effects
      of cigarette smoking on systemic inflammation and long-term risk for chronic
      obstructive pulmonary disease and all-cause mortality.

PMID- 19581278
TI  - Anti-infliximab and anti-adalimumab antibodies in relation to response to
      adalimumab in infliximab switchers and anti-tumour necrosis factor naive
      patients: a cohort study.
AB  - OBJECTIVE: To investigate how antibodies against anti-tumour necrosis factor
      (anti-TNF) agents influence response after switching from infliximab to
      adalimumab in rheumatoid arthritis (RA). METHODS: This cohort study consisted of
      235 patients with RA, all treated with adalimumab. At baseline 52 patients (22%)
      had been previously treated with infliximab ('switchers'), and 183 (78%) were
      anti-TNF naive. Disease activity (using the 28-joint count Disease Activity Score
      (DAS28)) and presence of antibodies against infliximab and adalimumab were
      assessed. Clinical response to adalimumab was compared between switchers and anti
      TNF naive patients and their anti-infliximab and anti-adalimumab antibody status.
      RESULTS: After 28 weeks of adalimumab treatment the decrease in DAS28 (Delta
      DAS28) for the 235 patients was 1.6+/-1.5 (mean+/-SD). Anti-adalimumab antibodies
      were detected in 46 patients (20%). Delta DAS28 was 1.8+/-1.4 in patients without
      anti-adalimumab and 0.6+/-1.3 in patients with anti-adalimumab (p<0.0001). Thirty
      three of the 52 switchers (63%) had anti-infliximab antibodies. Patients with
      anti-infliximab more often developed anti-adalimumab than anti-TNF naive patients
      (11 (33%) vs 32 (18%); p=0.039). Delta DAS28 was greater for anti-TNF naive
      patients (1.7+/-1.5) than for switchers without anti-infliximab antibodies (Delta
      DAS28=0.9+/-1.4) (p=0.009). Delta DAS28 for switchers with anti-infliximab was
      1.2+/-1.3 and did not differ significantly from anti-TNF naive patients
      (p=0.262). CONCLUSION: Switchers with anti-infliximab antibodies more often
      develop antibodies against adalimumab than anti-TNF naive patients. Response to
      adalimumab was limited in switchers without anti-infliximab antibodies, which
      raises the question whether a second anti-TNF treatment should be offered to
      patients with RA for whom an initial treatment with an anti-TNF blocker fails, in
      the absence of anti-biological antibodies.

PMID- 19581279
TI  - Changes in the rates of joint surgery among patients with rheumatoid arthritis in
      California, 1983-2007.
AB  - BACKGROUND: Treatment of patients with rheumatoid arthritis (RA) has improved
      markedly over the past 25 years. OBJECTIVE: To investigate whether rates of joint
      surgery, a long-term consequence of poorly controlled RA, have changed over this
      period. METHODS: In this population-based, serial cross-sectional study of
      patients with RA aged >or=40 years in California, trends in annual rates of total
      knee arthroplasty, total hip arthroplasty, total ankle arthroplasty or
      arthrodesis and total wrist arthroplasty or arthrodesis from 1983 to 2007 were
      examined. RESULTS: Rates of joint surgery peaked in the 1990 s and since have
      decreased. Among patients aged 40-59 years, rates of knee surgery in 2003-2007
      were 19% lower than in 1983-1987 (adjusted rate ratio 0.81; 95% CI 0.74 to 0.87,
      p<0.0001), while rates of hip surgery in 2003-2007 were 40% lower (p<0.0001).
      Rates of knee and hip surgery did not decrease in patients aged >or=60 years but
      increased as observed in the general population. Compared with rates of ankle and
      wrist surgery in the mid-1980s, rates in the mid-2000s decreased significantly in
      both age groups. CONCLUSIONS: Rates of joint surgery in RA peaked in the 1990 s
      and have declined thereafter, suggesting that longterm outcomes of RA are
      improving.

PMID- 19581280
TI  - Major improvements in health-related quality of life during the use of etanercept
      in patients with previously refractory juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate changes in health-related quality of life (HRQoL) in
      patients with refractory juvenile idiopathic arthritis (JIA) who are being
      treated with etanercept. METHODS: 53 patients with JIA from seven Dutch centres
      were included. HRQoL was measured by the Childhood Health Assessment
      Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index
      mark 3 (HUI3) at the start and after 3, 15 and 27 months of treatment. At the
      same time points the following JIA disease activity variables were collected;
      physician's global assessment through the visual analogue scale (VAS), number of
      active and limited joints and erythrocyte sedimentation rate. A statistical
      method linear mixed models was used to assess outcomes over time. RESULTS: During
      etanercept treatment both disease-specific and generic HRQoL outcomes improved
      dramatically. Significant improvements were shown after 3 months and these
      improvements continued at least up to 27 months of treatment. The disease
      specific CHAQ, including VAS pain and wellbeing, showed a significant improvement
      in all domains. The generic health-profile measure CHQ improved for all the
      health concepts except for "family cohesion", which was normal. The generic
      preference-based HUI3 showed impairment and, subsequently, significant
      improvement in the more specific domains ("pain", "ambulatory", "dexterity"). In
      accordance disease activity variables also improved significantly over time.
      CONCLUSION: This study shows that the HRQoL of patients with refractory JIA can
      be substantially improved by the use of etanercept for all aspects impaired by
      JIA. Information on HRQoL is crucial to understand the complete impact of
      etanercept treatment on patients with JIA and their families.

PMID- 19581281
TI  - Adverse events and factors associated with toxicity in patients with early
      rheumatoid arthritis treated with methotrexate tight control therapy: the CAMERA
      study.
AB  - OBJECTIVE: To evaluate toxicity profiles in patients with rheumatoid arthritis
      (RA) treated either according to an intensive or a conventional treatment
      strategy approach with methotrexate (MTX) and to study factors associated with
      MTX-related toxicity. METHODS: Data were used from the Computer-Assisted
      Management in Early Rheumatoid Arthritis (CAMERA) study, in which clinical
      efficacy of an intensive treatment strategy with MTX was more beneficial than a
      conventional treatment strategy approach. In this study, data on adverse events
      (AEs) were compared between the two strategy groups. Logistic regression analyses
      were used to identify possible associations between factors assessed at baseline
      and withdrawal due to MTX-related AEs or liver toxicity at follow-up. RESULTS:
      Although significantly more patients in the intensive strategy group experienced
      MTX-related AEs than in the conventional strategy group, all recorded AEs were
      relatively mild. A higher body mass index (BMI) was significantly associated with
      withdrawal due to MTX-related AEs in the multiple regression analyses (odds
      ratio=1.207, 95% confidence interval 1.02 to 1.44, p=0.033). There was a trend
      towards an association between diminished creatinine clearance and MTX
      withdrawal. For liver toxicity, increased serum liver enzymes at baseline were
      associated with liver toxicity during follow-up. CONCLUSION: Although the
      occurrence of AEs in the intensive strategy group was higher than in the
      conventional strategy group, the previously observed clinical efficacy of an
      intensive treatment strategy seems to outweigh the observed toxicity profiles.
      When starting MTX, attention should be given to patients with a high BMI and
      those with increased levels of liver enzymes and decreased renal function.

PMID- 19581283
TI  - The aged uterus: multifetal pregnancy outcome after ovum donation in older women.
AB  - BACKGROUND: We aimed to investigate whether multifetal pregnancies are at risk of
      more pregnancy complications in women of advanced age after ovum donation.
      METHODS: Pregnancy outcome in women after ovum donation aged 40 and above was
      extracted. Labor and delivery data as well as antenatal records of women carrying
      twins were compared with those of singletons, as well as to a control group of
      all twin pregnancies delivered at Sheba Medical Center during 2007. RESULTS: One
      hundred and twenty-five women after ovum donation aged > or = 40 were studied. Of
      those, 42 women carried twin pregnancies and 83 carried singletons. The 42 women
      carrying twins comprised the study group and were compared with 417 control women
      with twins. Mean maternal age was 49.2 +/- 4.3 years. Hypertensive complications
      (50%), diabetes in pregnancy (31%) and hospitalization in pregnancy (69%) were
      all extremely high in the study group. Mean gestational age at delivery was lower
      for the study group compared with controls (35.2 +/- 2.3 versus 35.7 +/- 2.6
      weeks), with 35.7% of infants in the study group born < or = 34 weeks gestation
      compared with 21.8% of controls, (OR: 1.99, 95% CI: 1.02-3.89). Mean birthweight
      was also significantly lower for study group infants compared with controls, with
      77% of study infants born <2500 g compared with only 60% of controls (OR: 2.22,
      95% CI: 1.3-3.77). CONCLUSIONS: Pregnancy in advanced maternal age women after
      ovum donation carrying twins is associated with significant maternal and fetal
      complications, with increased risks of prematurity and lower birthweight.
      Possibly, the aged uterus is less suitable for carrying a multifetal pregnancy
      than a younger uterus. Therefore, the alternative of transferring a single, good
      quality embryo should be the preferred option.

PMID- 19581282
TI  - Erythrina speciosa (Leguminosae-Papilionoideae) under soil water saturation:
      morphophysiological and growth responses.
AB  - BACKGROUND AND AIMS: Erythrina speciosa is a Neotropical tree that grows mainly
      in moist habitats. To characterize the physiological, morphological and growth
      responses to soil water saturation, young plants of E. speciosa were subjected
      experimentally to soil flooding. METHODS: Flooding was imposed from 2 to 4 cm
      above the soil surface in water-filled tanks for 60 d. Non-flooded (control)
      plants were well watered, but never flooded. The net CO(2) exchange (A(CO2)),
      stomatal conductance (g(s)) and intercellular CO(2) concentration (C(i)) were
      assessed for 60 d. Soluble sugar and free amino acid concentrations and the
      proportion of free amino acids were determined at 0, 7, 10, 21, 28 and 45 d of
      treatments. After 28, 45 and 60 d, dry masses of leaves, stems and roots were
      determined. Stem and root cross-sections were viewed using light microscopy. KEY
      RESULTS: The A(CO2) and g(s) were severely reduced by flooding treatment, but
      only for the first 10 d. The soluble sugars and free amino acids increased until
      the tenth day but decreased subsequently. The content of asparagine in the roots
      showed a drastic decrease while those of alanine and gamma-aminobutyric increased
      sharply throughout the first 10 d after flooding. From the 20th day on, the
      flooded plants reached A(CO2) and g(s) values similar to those observed for non
      flooded plants. These events were coupled with the development of lenticels,
      adventitious roots and aerenchyma tissue of honeycomb type. Flooding reduced the
      growth rate and altered carbon allocation. The biomass allocated to the stem was
      higher and the root mass ratio was lower for flooded plants when compared with
      non-flooded plants. CONCLUSIONS: Erythrina speciosa showed 100 % survival until
      the 60th day of flooding and was able to recover its metabolism. The recovery
      during soil flooding seems to be associated with morphological alterations, such
      as development of hypertrophic lenticels, adventitious roots and aerenchyma
      tissue, and with the maintenance of neutral amino acids in roots under long-term
      exposure to root-zone O(2) deprivation.

PMID- 19581284
TI  - Familial hypophosphatemic rickets caused by a large deletion in PHEX gene.
AB  - CONTEXT: X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant
      and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR) share common
      clinical features including high fibroblast growth factor 23 (FGF23) levels.
      These diseases are caused by mutations in phosphate regulating endopeptidase
      homolog, X-linked (PHEX), FGF23, and dentin matrix acidic phosphoprotein 1 (DMP1)
      gene respectively. It remains unclear whether these diseases can be clinically
      discriminated. OBJECTIVE: To clarify the underlying mechanism of patients with
      hypophosphatemic rickets whose parents showed no physical findings suggesting
      rickets. DESIGN AND PATIENTS: The proband is a 39-year-old woman. She and her 37
      year-old brother show the same clinical features such as bowing of legs together
      with hypophosphatemia (sister: P 1.8 mg/dl, brother: P 1.6 mg/dl) and high FGF23
      levels (sister: 542 pg/ml, brother: 96 pg/ml). Physical findings of their parents
      are normal and ARHR was suspected. RESULTS: Sequencing of all coding exons and
      exon-intron junctions of DMP1 and FGF23 genes showed no mutation. Subsequent
      analysis revealed that there is a deletion of 52 143 bp including exons 1-3 in
      PHEX gene in the brother. His sister was found to be a heterozygote for the same
      deletion indicating that they are suffering from XLH. The same deletion was
      detected in the mother. However, the amount of the wild-type allele was more and
      that of the mutant one was less in genomic DNA from the mother compared with
      those from the sister. Single nucleotide polymorphism (SNP) analysis indicated
      that the mother has three kinds of PHEX alleles suggesting a somatic mosaicism.
      CONCLUSION: Careful genetic analysis is mandatory for correct differential
      diagnosis of hypophosphatemic rickets with high FGF23 levels.

PMID- 19581285
TI  - Subclinical hyperthyroidism and blood pressure in a population-based prospective
      cohort study.
AB  - OBJECTIVES: There is current controversy on the association between subclinical
      hyperthyroidism and hypertension. Data from cohort studies have not been
      available yet. The present study was designed to longitudinally investigate
      possible associations of subclinical hyperthyroidism with blood pressure, pulse
      pressure and the risk of hypertension. METHODS: We used data from the population
      based, prospective cohort Study of Health in Pomerania and included 2910 subjects
      (1469 women) aged 20-79 years with completed 5-year examination follow-up.
      Subjects with increased serum TSH levels or overt hyperthyroidism were excluded.
      Serum TSH levels below 0.25 mIU/l with free triiodothyronine and free thyroxine
      levels within the reference range were defined as subclinical hyperthyroidism.
      Blood pressure was measured according to standard methods. RESULTS: Multivariable
      analyses adjusted for age, sex, overweight, obesity, smoking status and time
      between the examinations did not reveal any statistically significant association
      between subclinical hyperthyroidism and any of the blood pressure-related
      variables in the whole study population. Although the 5-year hypertension
      incidence was higher in subjects with subclinical hyperthyroidism compared with
      those without (31.4 vs 19.2%; risk ratio 1.64; 95% confidence interval (CI) 1.17
      2.28, P=0.006), both groups did not differ with respect to the risk of
      hypertension, after analyses were adjusted for confounders (relative risk 1.23,
      95% CI 0.91-1.68, P=0.182). Analyses yielded similar results in subjects without
      thyroid disease and in those who took no antihypertensive medication. CONCLUSION:
      Subclinical hyperthyroidism is not associated with changes in blood pressure,
      pulse pressure or incident hypertension.

PMID- 19581286
TI  - Functional connection between deimination and deacetylation of histones.
AB  - Histone methylation plays key roles in regulating chromatin structure and
      function. The recent identification of enzymes that antagonize or remove histone
      methylation offers new opportunities to appreciate histone methylation plasticity
      in the regulation of epigenetic pathways. Peptidylarginine deiminase 4 (PADI4;
      also known as PAD4) was the first enzyme shown to antagonize histone methylation.
      PADI4 functions as a histone deiminase converting a methylarginine residue to
      citrulline at specific sites on the tails of histones H3 and H4. This activity is
      linked to repression of the estrogen-regulated pS2 promoter. Very little is known
      as to how PADI4 silences gene expression. We show here that PADI4 associates with
      the histone deacetylase 1 (HDAC1). Kinetic chromatin immunoprecipitation assays
      revealed that PADI4 and HDAC1, and the corresponding activities, associate
      cyclically and coordinately with the pS2 promoter during repression phases.
      Knockdown of HDAC1 led to decreased H3 citrullination, concomitantly with
      increased histone arginine methylation. In cells with a reduced HDAC1 and a
      slightly decreased PADI4 level, these effects were more pronounced. Our data thus
      suggest that PADI4 and HDAC1 collaborate to generate a repressive chromatin
      environment on the pS2 promoter. These findings further substantiate the
      "transcriptional clock" concept, highlighting the dynamic connection between
      deimination and deacetylation of histones.

PMID- 19581287
TI  - Nuclear import of the glucocorticoid receptor-hsp90 complex through the nuclear
      pore complex is mediated by its interaction with Nup62 and importin beta.
AB  - Glucocorticoid receptor (GR) is cytoplasmic in the absence of ligand and
      localizes to the nucleus after steroid binding. Previous evidence demonstrated
      that the hsp90-based heterocomplex bound to GR is required for the efficient
      retrotransport of the receptor to the nuclear compartment. We examined the
      putative association of GR and its associated chaperone heterocomplex with
      structures of the nuclear pore. We found that importin beta and the integral
      nuclear pore glycoprotein Nup62 interact with hsp90, hsp70, p23, and the TPR
      domain proteins FKBP52 and PP5. Nup62 and GR were able to interact in a more
      efficient manner when chaperoned by the hsp90-based heterocomplex. Interestingly,
      the binding of hsp70 and p23 to Nup62 does not require the presence of hsp90,
      whereas the association of FKBP52 and PP5 is hsp90 dependent, as indicated by the
      results of experiments where the hsp90 function was disrupted with radicicol. The
      ability of both FKBP52 and PP5 to interact with Nup62 was abrogated in cells
      overexpressing the TPR peptide. Importantly, GR cross-linked to the hsp90
      heterocomplex was able to translocate to the nucleus in digitonin-permeabilized
      cells treated with steroid, suggesting that GR could pass through the pore in its
      untransformed state.

PMID- 19581289
TI  - Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional
      activation of genes implicated in oral cancer manifestation.
AB  - Nucleophosmin (NPM1) is a multifunctional protein involved in the regulation of
      centrosome duplication, ribosome biogenesis, genomic stability, histone chaperone
      function, and transcription. Overexpression of NPM1 is associated with cancers of
      diverse histological origins. Here, we have found that p300-mediated acetylation
      of NPM1 modulates its subcellular localization and augments its oncogenic
      potential. Acetylated NPM1 is predominantly localized in the nucleoplasm, where
      it associates with transcriptionally active RNA polymerase II. Deacetylation of
      NPM1 is brought about by human SIRT1 and reduces its transcriptional activation
      potential. Remarkably, increased levels of acetylated NPM1 were found in grade II
      and III oral squamous cell carcinoma (OSCC) patient samples. Small interfering
      RNA (siRNA)-mediated knockdown of NPM1 in an OSCC cell line, followed by
      microarray analysis and chromatin immunoprecipitation experiments, revealed that
      some of the genes involved in oral cancer malignancy are regulated by NPM1 and
      have acetylated NPM1 localized at their promoters. Either suppression of p300 by
      siRNA or mutation of acetylatable lysine residues of NPM1 resulted in reduced
      occupancy of acetylated NPM1 on the target gene promoter concomitant with its
      decreased transcript levels. These observations suggest that acetylated NPM1
      transcriptionally regulates genes involved in cell survival and proliferation
      during carcinogenesis.

PMID- 19581288
TI  - Phosphorylation of the transcription elongation factor Spt5 by yeast Bur1 kinase
      stimulates recruitment of the PAF complex.
AB  - The Saccharomyces cerevisiae kinase Bur1 is involved in coupling transcription
      elongation to chromatin modification, but not all important Bur1 targets in the
      elongation complex are known. Using a chemical genetics strategy wherein Bur1
      kinase was engineered to be regulated by a specific inhibitor, we found that Bur1
      phosphorylates the Spt5 C-terminal repeat domain (CTD) both in vivo and in
      isolated elongation complexes in vitro. Deletion of the Spt5 CTD or mutation of
      the Spt5 serines targeted by Bur1 reduces recruitment of the PAF complex, which
      functions to recruit factors involved in chromatin modification and mRNA
      maturation to elongating polymerase II (Pol II). Deletion of the Spt5 CTD showed
      the same defect in PAF recruitment as rapid inhibition of Bur1 kinase activity,
      and this Spt5 mutation led to a decrease in histone H3K4 trimethylation. Brief
      inhibition of Bur1 kinase activity in vivo also led to a significant decrease in
      phosphorylation of the Pol II CTD at Ser-2, showing that Bur1 also contributes to
      Pol II Ser-2 phosphorylation. Genetic results suggest that Bur1 is essential for
      growth because it targets multiple factors that play distinct roles in
      transcription.

PMID- 19581291
TI  - A noncanonical bromodomain in the AAA ATPase protein Yta7 directs chromosomal
      positioning and barrier chromatin activity.
AB  - Saccharomyces cerevisiae Yta7 is a barrier active protein that modulates
      transcriptional states at the silent mating locus, HMR. Additionally, Yta7
      regulates histone gene transcription and has overlapping functions with known
      histone chaperones. This study focused on deciphering the functional role of the
      noncanonical Yta7 bromodomain. By use of genetic and epistasis analyses, the Yta7
      bromodomain was shown to be necessary for barrier activity at HMR and to have
      overlapping functions with histone regulators (Asf1 and Spt16). Canonical
      bromodomains can bind to acetylated lysines on histones; however, the Yta7
      bromodomain showed an association with histones that was independent of
      posttranslational modification. Further investigation showed that regions of Yta7
      other than the bromodomain conferred histone association. Chromatin
      immunoprecipitation-chip analyses revealed that the Yta7 bromodomain was not
      solely responsible for histone association but was also necessary for proper
      chromosomal positioning of Yta7. This work demonstrates that the Yta7 bromodomain
      engages histones for certain cellular functions like barrier chromatin
      maintenance and particular Spt16/Asf1 cellular pathways of chromatin regulation.

PMID- 19581290
TI  - Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer.
AB  - A prominent hallmark of most human cancer is aneuploidy, which is a result of the
      chromosomal instability of cancer cells and is thought to contribute to the
      initiation and progression of most carcinomas. The developmentally regulated
      GATA6 transcription factor is commonly lost in ovarian cancer, and the loss of
      its expression is closely associated with neoplastic transformation of the
      ovarian surface epithelium. In the present study, we found that reduction of
      GATA6 expression with small interfering RNA (siRNA) in human ovarian surface
      epithelial cells resulted in deformation of the nuclear envelope, failure of
      cytokinesis, and formation of polyploid and aneuploid cells. We further
      discovered that loss of the nuclear envelope protein emerin may mediate the
      consequences of GATA6 suppression. The nuclear phenotypes were reproduced by
      direct suppression of emerin with siRNA. Thus, we conclude that diminished
      expression of GATA6 leads to a compromised nuclear envelope that is causal for
      polyploidy and aneuploidy in ovarian tumorigenesis. The loss of emerin may be the
      basis of nuclear morphological deformation and subsequently the cause of
      aneuploidy in ovarian cancer cells.

PMID- 19581293
TI  - A retrospective analysis of terlipressin in bolus for the management of
      refractory vasoplegic hypotension after cardiac surgery.
AB  - Cardiac surgery performed with cardiopulmonary bypass (CPB) may be complicated by
      hypotension due to low systemic vascular resistance (SVR). Often in those cases,
      hypotension is resistant to pressor catecholamines. We report six cases of
      norepinephrine-resistant postcardiotomy hypotension, treated by terlipressin
      (TP), a potent vasopressor agent. Between May 2007 and May 2008, we treated six
      patients with TP administration (1 mg bolus) for post CPB refractory vasodilatory
      hypotension. Analyzed parameters were: mean arterial pressure (m-AP), SVR,
      cardiac output index (CI), mean pulmonary pressure (m-PP), and lactate, at
      baseline (before TP bolus) and 3 h after injection. Before TP bolus, the average
      m-AP was 53.32+/-8.86 mmHg, the CI was 3.45+/-0.24 l/min/m(2), the SVR was 650+/
      62.03 dyne*s/cm(5) and the arterial lactate level was 4.6+/-0.95 mmol/l. Three
      hours after the TP bolus, the m-AP increased to 81.83+/-9.71 mmHg (P=0.002), the
      CI decreased to 2.88+/-0.14 l/min/m(2) (P=0.002), the SVR increased to 1154+/-116
      dyne*s/cm(5) (P=0.002), and arterial lactates decreased to 3.13+/-0.78 mmol/l
      (P=0.015), without significant modification of m-PP and CVP. We treated
      postoperative refractory low SVR hypotension by TP administration in bolus.
      Exogenous administration of TP normalized SVR and increased the systemic arterial
      pressure with a minimum effect on pulmonary pressure. Subsequently, the effect on
      systemic blood pressure enhanced urine output. No major collateral effects were
      observed. The administration of TP in bolus may result as a useful alternative
      for treating refractory low SVR hypotension post CPB.

PMID- 19581292
TI  - The Drosophila metastasis suppressor gene Nm23 homolog, awd, regulates epithelial
      integrity during oogenesis.
AB  - The expression levels of the metastasis suppressor gene Nm23 have been shown to
      correlate positively or inversely with prognosis in different cancer cohorts.
      This indicates that Nm23 may be needed at different expression levels and may
      function differently in various tissues. Here we report a novel epithelial
      function of the Drosophila melanogaster homolog of human Nm23, abnormal wing
      discs (awd). We show a dynamic expression pattern of the Awd protein during
      morphogenesis of the Drosophila follicle cells during oogenesis. Loss-of-function
      awd mutant cells result in the accumulation and spreading of adherens junction
      components, such as Drosophila E-cadherin, beta-catenin/Armadillo, and alpha
      spectrin, and the disruption of epithelial integrity, including breaking up of
      the epithelial sheet and piling up of follicle cells. In contrast, overexpression
      of awd diminishes adherens junction components and induces a mesenchymal-cell
      like cell shape change. The gain-of-function phenotype is consistent with a
      potential oncogenic function of this metastasis suppressor gene. Interestingly,
      we demonstrate that the epithelial function of awd is mediated by Rab5 and show
      that the Rab5 expression level is downregulated in awd mutant cells. Therefore,
      awd modulates the level and localization of adherens junction components via
      endocytosis. This is the first demonstration of an in vivo function of Nm23
      family genes in regulating epithelial morphogenesis.

PMID- 19581294
TI  - Aortoesophageal fistula: an uncommon complication after stent-graft repair of an
      aortic thoracic aneurysm.
AB  - OBJECTIVES: To report the incidence and management of aortoesophageal fistula
      (AEF) secondary to endovascular stent-graft repair of the descending thoracic
      aorta. METHODS: We analyze a case of AEF as a late complication of stent-graft
      repair of a thoracic aortic aneurysm in a 74-year-old male. We also include a
      discussion on alternatives of treatment based on a review of the literature
      currently available in MEDLINE. RESULTS: This patient was admitted to our
      hospital because of constitutional symptoms. The diagnosis was established by
      computed tomography and upper gastrointestinal endoscopy. The patient died 50
      days after admission. CONCLUSIONS: AEF is a catastrophic complication of
      endovascular stent-graft placement. Treatment options are very limited, as these
      patients are usually not candidates for open surgery. Conservative treatment is
      often associated with fatal results.

PMID- 19581295
TI  - Heterogeneous nuclear ribonucleoprotein R enhances transcription from the
      naturally configured c-fos promoter in vitro.
AB  - Transcription of a proto-oncogene c-fos is induced rapidly to high levels by
      various extracellular stimuli. To explore the molecular mechanism of c-fos gene
      induction, we established a defined in vitro transcription system for the c-fos
      promoter that consists of purified activators (SRF, Elk-1, cAMP-responsive
      element-binding protein, and ATF1), general transcription factors, and RNA
      polymerase II. In this reconstituted transcription system, activation of c-fos
      transcription was highly dependent upon coactivators such as PC4 and Mediator,
      indicating a very weak activation potential of the activators in the context of
      an unaltered promoter structure. This heightened coactivator dependence, however,
      allowed us to identify from HeLa nuclear extract a coactivator-like activity
      termed transcriptional regulator of c-fos (TREF) that enhanced c-fos
      transcription but not GAL4-VP16-dependent transcription. TREF cooperated with
      Mediator to enhance c-fos transcription by approximately 60-fold over its basal
      level and, like Mediator, stimulated activator-independent (basal) transcription
      as well. Further purification of TREF revealed that it consists of at least three
      distinct components, one of which was purified to near homogeneity and identified
      as heterogeneous nuclear ribonucleoprotein R. Recombinant heterogeneous nuclear
      ribonucleoprotein R enhanced transcription from the c-fos promoter and displayed
      cooperativity with PC4 and Mediator, thus demonstrating its direct
      transcriptional activity.

PMID- 19581296
TI  - New insights into how the Rho guanine nucleotide dissociation inhibitor regulates
      the interaction of Cdc42 with membranes.
AB  - The subcellular localization of the Rho family GTPases is of fundamental
      importance to their proper functioning in cells. The Rho guanine nucleotide
      dissociation inhibitor (RhoGDI) plays a key regulatory role by influencing the
      cellular localization of Rho GTPases and is essential for the transforming
      activity of oncogenic forms of Cdc42. However, the mechanism by which RhoGDI
      helps Cdc42 to undergo the transition between a membrane-associated protein and a
      soluble (cytosolic) species has been poorly understood. Here, we examine how
      RhoGDI influences the binding of Cdc42 to lipid bilayers. Despite having similar
      affinities for the signaling-inactive (GDP-bound) and signaling-active (GTP
      bound) forms of Cdc42 in solution, we show that when RhoGDI interacts with Cdc42
      along the membrane surface, it has a much higher affinity for GDP-bound Cdc42
      compared with its GTP-bound counterpart. Interestingly, the rate for the
      dissociation of Cdc42.RhoGDI complexes from membranes is unaffected by the
      nucleotide-bound state of Cdc42. Moreover, the membrane release of Cdc42.RhoGDI
      complexes occurs at a similar rate as the release of Cdc42 alone, with the major
      effect of RhoGDI being to impede the re-association of Cdc42 with membranes.
      These findings lead us to propose a new model for how RhoGDI influences the
      ability of Cdc42 to move between membranes and the cytosol, which highlights the
      role of the membrane in helping RhoGDI to distinguish between the GDP- and GTP
      bound forms of Cdc42 and holds important implications for how it functions as a
      key regulator of the cellular localization and signaling activities of this
      GTPase.

PMID- 19581297
TI  - Molecular chaperone Hsp70/Hsp90 prepares the mitochondrial outer membrane
      translocon receptor Tom71 for preprotein loading.
AB  - The preproteins targeted to the mitochondria are transported through the
      translocase of the outer membrane complex. Tom70/Tom71 is a major surface
      receptor of the translocase of the outer membrane complex for mitochondrial
      preproteins. The preproteins are escorted to Tom70/Tom71 by molecular chaperones
      Hsp70 and Hsp90. Here we present the high resolution crystal structures of Tom71
      and the protein complexes between Tom71 and the Hsp70/Hsp90 C terminus. The
      crystal structures indicate that Tom70/Tom71 may exhibit two distinct states. In
      the closed state, the N-terminal domain of Tom70/Tom71 partially blocks the
      preprotein-binding pocket. In the open state, the N-terminal domain moves away,
      and the preprotein-binding pocket is fully exposed. The complex formation between
      the C-terminal EEVD motif of Hsp70/Hsp90 and Tom71 could lock Tom71 in the open
      state where the preprotein-binding pocket of Tom71 is ready to receive
      preproteins. The interactions between Hsp70/Hsp90 and Tom71 N-terminal domain
      generate conformational changes that may increase the volume of the preprotein
      binding pocket. The complex formation of Hsp70/Hsp90 and Tom71 also generates
      significant domain rearrangement within Tom71, which may position the preprotein
      binding pocket closer to Hsp70/Hsp90 to facilitate the preprotein transfer from
      the molecular chaperone to Tom71. Therefore, molecular chaperone Hsp70/Hsp90 may
      function to prepare the mitochondrial outer membrane receptor Tom71 for
      preprotein loading.

PMID- 19581298
TI  - ERK5 activity is required for nerve growth factor-induced neurite outgrowth and
      stabilization of tyrosine hydroxylase in PC12 cells.
AB  - Extracellular signal-regulated kinases (ERKs) play important physiological roles
      in proliferation, differentiation, and gene expression. ERK5 is approximately
      twice the size of ERK1/2, and its amino-terminal half contains the kinase domain
      that shares homology with ERK1/2 and TEY activation motif, whereas the carboxyl
      terminal half is unique. In this study, we examined a physiological role of ERK5
      in rat pheochromocytoma cells (PC12), comparing it with ERK1/2. Nerve growth
      factor (NGF) induced phosphorylation of both ERK5 and ERK1/2, whereas the cAMP
      analog dibutyryl cAMP (Bt(2)cAMP) caused only ERK1/2 phosphorylation. U0126, at
      30 mum, that blocks ERK1/2 signaling selectively attenuated neurite outgrowth
      induced by NGF and Bt(2)cAMP, but BIX02188 and BIX02189, at 30 mum, that block
      ERK5 signaling and an ERK5 dominant-negative mutant suppressed only NGF-induced
      neurite outgrowth. Next, we examined the expression of tyrosine hydroxylase, a
      rate-limiting enzyme of catecholamine biosynthesis. Both NGF and Bt(2)cAMP
      increased tyrosine hydroxylase gene promoter activity in an ERK1/2-dependent
      manner but was ERK5-independent. However, when both ERK5 and ERK1/2 signalings
      were inhibited, tyrosine hydroxylase protein up-regulation by NGF and Bt(2)cAMP
      was abolished, because of the loss of stabilization of tyrosine hydroxylase
      protein by ERK5. Taking these results together, ERK5 is involved in neurite
      outgrowth and stabilization of tyrosine hydroxylase in PC12 cells, and ERK5,
      along with ERK1/2, plays essential roles in the neural differentiation process.

PMID- 19581299
TI  - In vivo mutational analysis of YtvA from Bacillus subtilis: mechanism of light
      activation of the general stress response.
AB  - The general stress response of Bacillus subtilis can be activated by stimuli such
      as the addition of salt or ethanol and with blue light. In the latter response,
      YtvA activates sigma(B) through a cascade of Rsb proteins, organized in
      stressosomes. YtvA is composed of an N-terminal LOV (light, oxygen, and voltage)
      domain and a C-terminal STAS (sulfate transporter and anti-sigma factor) domain
      and shows light-modulated GTP binding in vitro. Here, we examine the mechanism of
      YtvA-mediated activation of sigma(B) in vivo with site-directed mutagenesis.
      Constitutive off and constitutive on mutations have been identified. Disruption
      of GTP binding in the STAS domain eliminates light activation of sigma(B). In
      contrast, modification of sites relevant for phosphorylation of STAS domains does
      not affect the stress response significantly. The data obtained are integrated
      into a model for the structure of full-length YtvA, which presumably functions as
      a dimer.

PMID- 19581300
TI  - Fibronectin binds to and induces conformational change in a disordered region of
      leptospiral immunoglobulin-like protein B.
AB  - Leptospira interrogans is a pathogenic spirochete that causes disease in both
      humans and animals. LigB (Leptospiral immunoglobulin-like protein B) contributes
      to the binding of Leptospira to extracellular matrix proteins such as fibronectin
      (Fn), fibrinogen, laminin, and collagen. A high affinity Fn-binding region of
      LigB has been recently localized to LigBCen2, which contains the partial eleventh
      and full twelfth immunoglobulin-like repeats (LigBCen2R) and 47 amino acids of
      the non-repeat region (LigBCen2NR) of LigB. In this study, LigBCen2NR was shown
      to bind to the N-terminal domain (NTD) of Fn (K(D) = 379 nm) by an enzyme-linked
      immunosorbent assay and isothermal titration calorimetry. Interestingly, this
      sequence was not observed to adopt secondary structure by far UV circular
      dichroism or by differential scanning calorimetry, in agreement with computer
      based secondary structure predictions. A low partition coefficient (K(av))
      measured with gel permeation chromatography, a high hydrodynamic radius (R(h))
      measured with dynamic light scattering, and the insensitivity of the intrinsic
      viscosity to guanidine hydrochloride treatment all suggest that LigBCen2NR
      possesses an extended and disordered structure. Two-dimensional (15)N-(1)H HSQC
      NMR spectra of intact LigBCen2 in the absence and presence of NTD are consistent
      with these observations, suggesting the presence of both a beta-rich region and
      an unstructured region in LigBCen2 and that the latter of these selectively
      interacts with NTD. Upon binding to NTD, LigBCen2NR was observed by CD to adopt a
      beta-strand-rich structure, suggestive of the known beta-zipper mode of NTD
      binding.

PMID- 19581301
TI  - Accelerated fatty acid oxidation in muscle averts fasting-induced hepatic
      steatosis in SJL/J mice.
AB  - The accumulation of triglycerides (TG) in the liver, designated hepatic
      steatosis, is characteristically associated with obesity and insulin resistance,
      but it can also develop after fasting. Here, we show that fasting-induced hepatic
      steatosis is under genetic control in inbred mice. After a 24-h fast, C57BL/6J
      mice and SJL/J mice both lost more than 20% of body weight and approximately 60%
      of total body TG. In C57BL/6J mice, TG accumulated in liver, producing frank
      steatosis. In striking contrast, SJL/J mice failed to accumulate any hepatic TG
      even though they lost nearly as much adipose tissue mass as the C57BL/6J mice.
      Mice from five other inbred strains developed fasting-induced steatosis like the
      C57BL/6J mice. Measurements of the uptake of free fatty acids (FA) in vivo and in
      vitro demonstrated that SJL/J mice were protected from steatosis because their
      heart and skeletal muscle took up and oxidized twice as much FA as compared with
      C57BL/6J mice. As a result of this muscle diversion, serum-free FA and ketone
      bodies rose much less after fasting in SJL/J mice as compared with C57BL/6J mice.
      When livers of SJL/J and C57BL/6J mice were perfused with similar concentrations
      of FA, the livers took up and esterified similar amounts. We conclude that SJL/J
      mice express one or more variant genes that lead to enhanced FA uptake and
      oxidation in muscle, thereby sparing the liver from FA overload in the fasting
      state.

PMID- 19581302
TI  - Role of intramembrane polar residues in the YgfO xanthine permease: HIS-31 and
      ASN-93 are crucial for affinity and specificity, and ASP-304 and GLU-272 are
      irreplaceable.
AB  - Using the YgfO xanthine permease of Escherichia coli as a bacterial model for the
      study of the evolutionarily ubiquitous nucleobase-ascorbate transporter
      (NAT/NCS2) family, we performed a systematic Cys-scanning and site-directed
      mutagenesis of 14 putatively charged (Asp, Glu, His, Lys, or Arg) and 7 highly
      polar (Gln or Asn) residues that are predicted to lie in transmembrane helices
      (TMs). Of 21 single-Cys mutants engineered in the background of a functional YgfO
      devoid of Cys residues (C-less), only four are inactive or have marginal activity
      (H31C, N93C, E272C, D304C). The 4 residues are conserved throughout the family in
      TM1 (His-31), TM3 (Asn-93/Ser/Thr), TM8 (Glu-272), and putative TM9a (Asp
      304/Asn/Glu). Extensive site-directed mutagenesis in wild-type background showed
      that H31N and H31Q have high activity and affinity for xanthine but H31Q
      recognizes novel purine bases and analogues, whereas H31C and H31L have impaired
      affinity for xanthine and analogues, and H31K or H31R impairs expression in the
      membrane. N93S and N93A are highly active but more promiscuous for recognition of
      analogues at the imidazole moiety of substrate, N93D has low activity, N93T has
      low affinity for xanthine or analogues, and N93Q or N93C is inactive. All mutants
      replacing Glu-272 or Asp-304, including E272D, E272Q, D304E, and D304N, are
      inactive, although expressed to high levels in the membrane. Finally, one of the
      17 assayable single-Cys mutants, Q258C, was sensitive to inactivation by N
      ethylmaleimide. The findings suggest that polar residues important for the
      function of YgfO cluster in TMs 1, 3, 8 and 9a.

PMID- 19581303
TI  - Pore mutations in ammonium transporter AMT1 with increased electrogenic ammonium
      transport activity.
AB  - AMT/Mep ammonium transporters mediate high affinity ammonium/ammonia uptake in
      bacteria, fungi, and plants. The Arabidopsis AMT1 proteins mediate uptake of the
      ionic form of ammonium. AMT transport activity is controlled allosterically via a
      highly conserved cytosolic C terminus that interacts with neighboring subunits in
      a trimer. The C terminus is thus capable of modulating the conductivity of the
      pore. To gain insight into the underlying mechanism, pore mutants suppressing the
      inhibitory effect of mutations in the C-terminal trans-activation domain were
      characterized. AMT1;1 carrying the mutation Q57H in transmembrane helix I (TMH I)
      showed increased ammonium uptake but reduced capacity to take up methylammonium.
      To explore whether the transport mechanism was altered, the AMT1;1-Q57H mutant
      was expressed in Xenopus oocytes and analyzed electrophysiologically. AMT1;1-Q57H
      was characterized by increased ammonium-induced and reduced methylammonium
      induced currents. AMT1;1-Q57H possesses a 100x lower affinity for ammonium (K(m))
      and a 10-fold higher V(max) as compared with the wild type form. To test whether
      the trans-regulatory mechanism is conserved in archaeal homologs, AfAmt-2 from
      Archaeoglobus fulgidus was expressed in yeast. The transport function of AfAmt-2
      also depends on trans-activation by the C terminus, and mutations in pore
      residues corresponding to Q57H of AMT1;1 suppress nonfunctional AfAmt-2 mutants
      lacking the activating C terminus. Altogether, our data suggest that bacterial
      and plant AMTs use a conserved allosteric mechanism to control ammonium flux,
      potentially using a gating mechanism that limits flux to protect against ammonium
      toxicity.

PMID- 19581304
TI  - Identification of residues in the drug translocation pathway of the human
      multidrug resistance P-glycoprotein by arginine mutagenesis.
AB  - P-glycoprotein (P-gp, ATP-binding cassette B1) is a drug pump that extracts toxic
      drug substrates from the plasma membrane and catalyzes their ATP-dependent
      efflux. To map the residues in the drug translocation pathway, we performed
      arginine-scanning mutagenesis on all transmembrane (TM) segments (total = 237
      residues) of a P-gp processing mutant (G251V) defective in folding (15%
      maturation efficiency) (glycosylation state used to monitor folding). The
      rationale was that arginines introduced into the drug-binding sites would mimic
      drug rescue and enhance maturation of wild-type or processing mutants of P-gp. It
      was found that 38 of the 89 mutants that matured had enhanced maturation.
      Enhancer mutations were found in 11 of the 12 TM segments with the largest number
      found in TMs 6 and 12 (seven in each), TMs that are critical for P-gp-drug
      substrate interactions. Modeling of the TM segments showed that the enhancer
      arginines were found on the hydrophilic face, whereas inhibitory arginines were
      located on a hydrophobic face that may be in contact with the lipid bilayer. It
      was found that many of the enhancer arginines caused large alterations in P-gp
      drug interactions in ATPase assays. For example, mutants A302R (TM5), L339R
      (TM6), G872R (TM10), F942R (TM11), Q946R (TM11), V982R (TM12), and S993R (TM12)
      reduced the apparent affinity for verapamil by approximately 10-fold, whereas the
      F336R (TM6) and M986R (TM12) mutations caused at least a 10-fold increase in
      apparent affinity for rhodamine B. The results suggest that P-gp contains a large
      aqueous-filled drug translocation pathway with multiple drug-binding sites that
      can accommodate the bulky arginine side chains to promote folding of the protein.

PMID- 19581305
TI  - Modulation of calcium oxalate dihydrate growth by selective crystal-face binding
      of phosphorylated osteopontin and polyaspartate peptide showing occlusion by
      sectoral (compositional) zoning.
AB  - Calcium oxalate dihydrate (COD) mineral and the urinary protein
      osteopontin/uropontin (OPN) are commonly found in kidney stones. To investigate
      the effects of OPN on COD growth, COD crystals were grown with phosphorylated OPN
      or a polyaspartic acid-rich peptide of OPN (DDLDDDDD, poly-Asp(86-93)). Crystals
      grown with OPN showed increased dimensions of the {110} prismatic faces
      attributable to selective inhibition at this crystallographic face. At high
      concentrations of OPN, elongated crystals with dominant {110} faces were
      produced, often with intergrown, interpenetrating twin crystals. Poly-Asp(86-93)
      dose-dependently elongated crystal morphology along the {110} faces in a manner
      similar to OPN. In crystal growth studies using fluorescently tagged poly-Asp(86
      93) followed by imaging of crystal interiors using confocal microscopy, sectoral
      (compositional) zoning in COD was observed resulting from selective binding and
      incorporation (occlusion) of peptide exclusively into {110} crystal sectors.
      Computational modeling of poly-Asp(86-93) adsorption to COD {110} and {101}
      surfaces also suggests increased stabilization of the COD {110} surface and
      negligible change to the natively stable {101} surface. Ultrastructural,
      colloidal-gold immunolocalization of OPN by transmission electron microscopy in
      human stones confirmed an intracrystalline distribution of OPN. In summary, OPN
      and its poly-Asp(86-93) sequence similarly affect COD mineral growth; the {110}
      crystallographic faces become enhanced and dominant attributable to {110} face
      inhibition by the protein/peptide, and peptides can incorporate into the mineral
      phase. We, thus, conclude that the poly-Asp(86-93) domain is central to the OPN
      ability to interact with the {110} faces of COD, where it binds to inhibit
      crystal growth with subsequent intracrystalline incorporation (occlusion).

PMID- 19581306
TI  - Regulatory mechanism of matrix metalloprotease-2 enzymatic activity by factor Xa
      and thrombin.
AB  - Matrix metalloprotease (MMP)-2 plays a key role in many biological and
      pathological processes related to cell migration, invasion, and mitogenesis. MMP
      2 is synthesized as a zymogen that is activated through either a conformational
      change or proteolysis of the propeptide. Several activating enzymes for pro-MMP-2
      have been proposed, including metalloproteases and serine proteases. The
      mechanism of pro-MMP-2 activation by metalloproteases is well established, and
      the most studied activation mechanism involves cleavage of the propeptide by
      membrane type 1-MMP (MT1-MMP). In contrast, serine protease activation has not
      been thoroughly studied, although studies suggest that MT1-MMP may be involved in
      activation by thrombin and plasmin. Here, we demonstrate that factor Xa mediates
      MT1-MMP-independent processing of pro-MMP-2 in vascular smooth muscle cells and
      endothelial cells. Factor Xa and thrombin directly cleaved the propeptide on the
      carboxyl terminal sides of the Arg(98) and Arg(101) residues, whereas plasmin
      only cleaved the propeptide downstream of Arg(101). Moreover, processed MMP-2
      showed enzymatic activity that was enhanced by intermolecular autoproteolytic
      processing at the Asn(109)-Tyr peptide bond. In addition to its role in
      activation, factor Xa rapidly degraded MMP-2, thereby restricting excessive MMP-2
      activity. Thrombin also degraded MMP-2, but the degradation was reduced greatly
      under cell-associated conditions, resulting in an increase in processed MMP-2.
      Overall, factor Xa and thrombin regulate MMP-2 enzymatic activity through its
      activation and degradation. Thus, the net enzymatic activity results from a
      balance between MMP-2 activation and degradation.

PMID- 19581307
TI  - Identification and characterization of nucleolin as a c-myc G-quadruplex-binding
      protein.
AB  - myc is a proto-oncogene that plays an important role in the promotion of cellular
      growth and proliferation. Understanding the regulation of c-myc is important in
      cancer biology, as it is overexpressed in a wide variety of human cancers,
      including most gynecological, breast, and colon cancers. We previously
      demonstrated that a guanine-rich region upstream of the P1 promoter of c-myc that
      controls 85-90% of the transcriptional activation of this gene can form an
      intramolecular G-quadruplex (G4) that functions as a transcriptional repressor
      element. In this study, we used an affinity column to purify proteins that
      selectively bind to the human c-myc G-quadruplex. We found that nucleolin, a
      multifunctional phosphoprotein, binds in vitro to the c-myc G-quadruplex
      structure with high affinity and selectivity when compared with other known
      quadruplex structures. In addition, we demonstrate that upon binding, nucleolin
      facilitates the formation and increases the stability of the c-myc G-quadruplex
      structure. Furthermore, we provide evidence that nucleolin overexpression reduces
      the activity of a c-myc promoter in plasmid presumably by inducing and
      stabilizing the formation of the c-myc G-quadruplex. Finally, we show that
      nucleolin binds to the c-myc promoter in HeLa cells, which indicates that this
      interaction occurs in vivo. In summary, nucleolin may induce c-myc G4 formation
      in vivo.

PMID- 19581308
TI  - The protein scaffold NHERF-1 controls the amplitude and duration of localized
      protein kinase D activity.
AB  - Protein kinase D (PKD) transduces an abundance of signals downstream of
      diacylglycerol production. The mammalian PKD family consists of three isoforms,
      PKD1, PKD2, and PKD3; of these PKD1 and PKD2 contain PDZ-binding motifs at their
      carboxyl termini. Here we show that membrane-localized NHERF scaffold proteins
      provide a nexus for tightly controlled PKD signaling via a PDZ domain
      interaction. Using a proteomic array containing 96 purified PDZ domains, we have
      identified the first PDZ domain of NHERF-1 as an interaction partner for the PDZ
      binding motifs of both PKD1 and PKD2. A fluorescence resonance energy transfer
      based translocation assay reveals a transient association of PKD1 and PKD2 with
      NHERF-1 in live cells that is triggered by phorbol ester stimulation and,
      importantly, differs strikingly from the sustained translocation to plasma
      membrane. Targeting a fluorescence resonance energy transfer-based kinase
      activity reporter for PKD to NHERF scaffolds reveals a unique signature of PKD
      activation at the scaffold that is distinct from that of general cytosolic or
      plasma membrane activity. Specifically, agonist-evoked activation of PKD at the
      scaffold is rapid and sustained but blunted in magnitude when compared with
      cytosolic PKD. Thus, live cell imaging of PKD activity demonstrates
      ultrasensitive control of kinase signaling at the scaffold compared with bulk
      activity in the cytosol or at the plasma membrane.

PMID- 19581309
TI  - Haemodynamic events and localised parenchymal changes following transcatheter
      arterial chemoembolisation for hepatic malignancy: interpretation of imaging
      findings.
AB  - Following transcatheter arterial chemoembolisation (TACE), the appearances on CT
      or MR images are largely related to the chemical and ischaemic insults to the
      portal tract. Understanding the mechanism of TACE-induced changes is essential
      for radiologists in order to determine the therapeutic effect as well as to
      distinguish these changes from recurrent tumours. This pictorial review
      illustrates the haemodynamic and substantial parenchymal changes related to TACE
      for hepatic malignancy.

PMID- 19581311
TI  - The intravertebral cleft in benign vertebral compression fracture: the diagnostic
      performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI.
AB  - We compared the diagnostic performance of non-enhanced MRI and fat-suppressed
      contrast-enhanced MRI (CEMRI) in diagnosing intravertebral clefts in benign
      vertebral compression fractures (VCFs). We retrospectively reviewed 99
      consecutive patients who had undergone percutaneous vertebroplasty for VCFs. A
      cleft was defined as a signal void or hyperintense area on non-enhanced MRI (T(1)
      and T(2) weighted imaging) or as a hypointense area within a diffusely enhanced
      vertebra on CEMRI. A cleft was confirmed as a solid opacification on post
      procedural radiographs. The interobserver reliability and MRI diagnostic
      performance were evaluated. The interobserver reliability of non-enhanced MRI was
      substantial (k _ 0.698) and the interobserver reliability of CEMRI was almost
      perfect (k _ 0.836). Post-procedural radiographs showed solid cleft opacification
      in 32 out of the 99 cases. The sensitivity and specificity of non-enhanced MRI
      were 0.72 and 0.82 (observer 1) and 0.63 and 0.87 (observer 2), respectively. The
      sensitivity and specificity of CEMRI were 0.94 and 0.63 (observer 1) and 0.85 and
      0.60 (observer 2), respectively. The sensitivity of CEMRI was significantly
      higher than that of non-enhanced MRI, and the specificity of non-enhanced MRI was
      higher than that of CEMRI. CEMRI was highly reliable and sensitive, and non
      enhanced MRI was specific for intravertebral clefts. Therefore, spine MRIs,
      including CEMRI, could provide useful information about intravertebral clefts
      before percutaneous vertebroplasty.

PMID- 19581310
TI  - The effect of concurrent androgen deprivation and 3D conformal radiotherapy on
      prostate volume and clinical organ doses during treatment for prostate cancer.
AB  - In this study, we investigated the shrinking effect of concurrent three
      dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on
      prostate volume, and its possible impact on the dose received by the rectum and
      bladder during the course of 3D-CRT. The difference between the prostatic volumes
      determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT)
      following a 3D-CRT course was assessed in 52 patients with localised prostate
      carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT
      based measurements were assessed. The pre- and post-treatment mean prostate
      volumes for the whole study population were 49.7 cm(3) and 41.0 cm(3) (p _ 0.02),
      respectively. The study cohort was divided into two groups depending on the
      duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were
      designated as "short NAD" (< or =3 months; SNAD) and the remaining 29 (55.3%) as
      "long NAD" (>3 months; LNAD). Patients on SNAD experienced a significantly
      greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%;
      p _ 0.03). A significant increase in rectum V(40-60) values in PT-CT compared
      with PL-CT was demonstrated. LNAD patients had significantly higher rectal V(50
      70) values at PT-CT compared with the SNAD group. There was a significant decline
      in V(30)-V(75) bladder values in PT-CT compared with PL-CT in the SNAD group. In
      conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated
      when RT planning was performed within 3 months of NAD. However, this reduction
      and daily organ motion may lead to an unpredictable increase in rectal doses.

PMID- 19581312
TI  - The value of multidetector-row CT angiography for pre-operative planning of
      breast reconstruction with deep inferior epigastric arterial perforator flaps.
AB  - The deep inferior epigastric artery perforator (DIEP) flap has recently become
      the first option for breast reconstruction. However, the anatomy of the deep
      inferior epigastric artery varies greatly from one individual to another and even
      from one hemiabdomen to the other. An optimal pre-operative evaluation method
      that adequately maps the underlying vasculature has been lacking. The advent of
      multidetector-row CT (MDCT) angiography has proven highly accurate at detailing
      the vasculature, but no reports have documented its value during pre-operative
      planning. From December 2006 to May 2008, 22 consecutive patients who underwent
      MDCT angiography before breast reconstruction using DIEP flaps were selected as
      the test group, and 22 former patients who did not undergo MDCT before the same
      procedure were selected as the control group. The two groups were evaluated for
      the ratio of pre-operative redesign, intra-operative method changes, time spent
      on flap harvest and the ratio of flap-associated complications. The pre-operative
      redesign ratio was 22.7% in the test group and 0% in the control group. The intra
      operative method change ratio was 0% in the test group and 13.6% in the control
      group. The mean time spent on flap harvest was 2.8 +/- 0.2 h in the test group
      and 4.4 +/- 0.2 h in the control group (p<0.05). The flap complication rate was
      1/22 in the test group and 3/22 in the control group (p _ 0.04). In conclusion,
      use of MDCT angiography during pre-operative planning promotes a significant
      reduction in operating time and complication rate.

PMID- 19581313
TI  - High-precision radiotherapy for craniospinal irradiation: evaluation of three
      dimensional conformal radiotherapy, intensity-modulated radiation therapy and
      helical TomoTherapy.
AB  - This study aimed to establish the feasibility of intensity-modulated radiation
      therapy (IMRT) in craniospinal irradiation (CSI) using conventional linear
      accelerator (IMRT_LA) and compare it dosimetrically with helical TomoTherapy
      (IMRT_Tomo) and three-dimensional conformal radiotherapy (3DCRT). CT datasets of
      four previously treated patients with medulloblastoma were used to generate
      3DCRT, IMRT_LA and IMRT_Tomo plans. A CSI dose of 35 Gy was prescribed to the
      planning target volume (PTV). IMRT_LA plans for tall patients were generated
      using an intensity feathering technique. All plans were compared dosimetrically
      using standardised parameters. The mean volume of each PTV receiving at least 95%
      of the prescribed dose (V(95%)) was >98% for all plans. All plans resulted in a
      comparable dose homogeneity index (DHI) for PTV_brain. For PTV_spine, IMRT_Tomo
      achieved the highest mean DHI of 0.96, compared with 0.91 for IMRT_LA and 0.84
      for 3DCRT. The best dose conformity index was achieved by IMRT_Tomo for PTV_brain
      (0.96) and IMRT_LA for PTV_spine (0.83). The IMRT_Tomo plan was superior in terms
      of reduction of the maximum, mean and integral doses to almost all organs at risk
      (OARs). It also reduced the volume of each OAR irradiated to various dose levels,
      except for the lowest dose volume. The beam-on time was significantly longer in
      IMRT_Tomo. In conclusion, IMRT_Tomo for CSI is technically easier and potentially
      dosimetrically favourable compared with IMRT_LA and 3DCRT. IMRT for CSI can also
      be realised on a conventional linear accelerator even for spinal lengths
      exceeding maximum allowable field sizes. The longer beam-on time in IMRT_Tomo
      raises concerns about intrafraction motion and whole-body integral doses.

PMID- 19581314
TI  - Cardiovascular therapeutic uses of targeted ultrasound contrast agents.
AB  - The therapeutic use of ultrasound contrast agents (UCAs) is an emerging
      methodology with high potential for enhanced directed therapeutic gene, bioactive
      gas, drug, and stem cell delivery. Ultrasound-targeted microbubble destruction
      has already demonstrated feasibility for plasmid DNA delivery. Similarly,
      therapeutic ultrasound for thrombolysis treatment has been taken into the
      clinical setting, and the addition of UCAs for therapeutic delivery or enhanced
      effect through cavitation is a natural progression to this investigation.
      However, as with any new technique, safety needs to be first demonstrated before
      translation into clinical practice. This review article will focus on the
      development of UCAs for cardiac and vascular therapeutics as well as the
      limitations/concerns for the use of therapeutic ultrasound in clinical medicine
      in order to lay a foundation for investigators planning to enter this exciting
      field or for those who want to broaden their understanding.

PMID- 19581315
TI  - MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction:
      a new mechanism for ischaemic cardioprotection.
AB  - AIMS: The present study was designed to investigate whether the beneficial
      effects of beta-blocker propranolol are related to regulation of microRNA miR-1.
      METHODS AND RESULTS: We demonstrated that propranolol reduced the incidence of
      arrhythmias in a rat model of myocardial infarction by coronary artery occlusion.
      Overexpression of miR-1 was observed in ischaemic myocardium and strikingly,
      administration of propranolol reversed the up-regulation of miR-1 nearly back to
      the control level. In agreement with its miR-1-reducing effect, propranolol
      relieved myocardial injuries during ischaemia, restored the membrane
      depolarization and cardiac conduction slowing, by rescuing the expression of
      inward rectifying K(+) channel subunit Kir2.1 and gap junction channel connexin
      43. Our results further revealed that the beta-adrenoceptor-cAMP-Protein Kinase A
      (PKA) signalling pathway contributed to the expression of miR-1, and serum
      response factor (SRF), which is known as one of the transcriptional enhancers of
      miR-1, was up-regulated in ischaemic myocardium. Moreover, propranolol inhibited
      the beta-adrenoceptor-cAMP-PKA signalling pathway and suppressed SRF expression.
      CONCLUSION: We conclude that the beta-adrenergic pathway can stimulate expression
      of arrhythmogenic miR-1, contributing to ischaemic arrhythmogenesis, and beta
      blockers produce their beneficial effects partially by down-regulating miR-1,
      which might be a novel strategy for ischaemic cardioprotection.

PMID- 19581316
TI  - Reducing ischaemia/reperfusion injury through delta-opioid-regulated intrinsic
      cardiac adrenergic cells: adrenopeptidergic co-signalling.
AB  - AIMS: The purpose of this study was to determine whether intrinsic cardiac
      adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting
      synergistic adrenopeptidergic cardioprotection. METHODS AND RESULTS: In situ
      hybridization coupled with immunostaining demonstrated that ICA cells exclusively
      expressed CGRP mRNA and co-expressed CGRP and delta-opioid receptor in human and
      rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP
      release from ICA cells in human and rat hearts. The delta-opioid agonist [D
      Pen(25)]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated
      rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with
      DPDPE reduced infarct size (IS) by 51 +/- 16% (P < 0.01). Co-infusion of beta(2)
      adrenergic receptor (beta(2)-AR) and CGRP receptor (CGRP-R) antagonists increased
      IS by 62 +/- 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS
      reduction. Pre-treatment of ICA cell-myocyte co-culture with the beta(2)-AR/CGRP
      R antagonists increased myocyte death rate by 24 +/- 4% (P < 0.01) and abolished
      DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O(2)). In
      the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection.
      Supplementing ICA cell-depleted myocyte culture with beta(2)-AR/CGRP-R agonists
      reduced hypoxia/re-O(2)-induced myocyte death by 24 +/- 5% (P < 0.01), simulating
      endogenous neurohormonal effects of ICA cells. Western blot analysis showed that
      DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was
      abolished in the presence of beta(2)-AR/CGRP-R blockade. Terminal dUTP nick-end
      labelling staining analysis of the LV infarct zone demonstrated that DPDPE
      reduced myocyte apoptosis by 58 +/- 19% (P < 0.05), an effect that was eliminated
      in the presence of beta(2)-AR/CGRP-R blockade. Finally, echocardiography showed
      that DPDPE increased LV contractility in a manner dependent on beta-AR/CGRP-R
      stimulation. CONCLUSION: ICA cells constitute a delta-opioid-regulated
      adrenopeptidergic paracrine system conferring robust cardioprotection through
      beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic
      pathway during ischaemia/reperfusion.

PMID- 19581318
TI  - Who should receive Tamiflu for swine flu?

PMID- 19581320
TI  - US senator seeks information about medical faculty links to drug industry.

PMID- 19581317
TI  - Changes in white matter as determinant of global functional decline in older
      independent outpatients: three year follow-up of LADIS (leukoaraiosis and
      disability) study cohort.
AB  - OBJECTIVE: To assess the impairment in daily living activities in older people
      with age related changes in white matter according to the severity of these
      changes. DESIGN: Observational data collection and follow-up of a cohort of older
      people undergoing brain magnetic resonance imaging after non-disabling
      complaints. SETTING: 11 European centres. PARTICIPANTS: 639 non-disabled older
      patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance
      imaging showed mild, moderate, or severe age related changes in white matter
      (Fazekas scale). Magnetic resonance imaging assessment also included cerebral
      infarcts and atrophy. MAIN OUTCOME MEASURE: Transition from no disability
      (defined as a score of 0 or 1 on the instrumental activities of daily living
      scale) to disability (score >/=2) or death over three year follow-up. Secondary
      outcomes were incident dementia and stroke. RESULTS: Over a mean follow-up period
      of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was
      available for 633 patients. The annual rate of transition or death was 10.5%,
      15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age
      related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox
      model comparing severe with mild changes and adjusted for clinical factors of
      functional decline, the risk of transition to disability or death was more than
      twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The
      other predictors were age group, history of atrial fibrillation, and complaint of
      gait disturbances. The effect of severe changes remained significant
      independently of baseline degree of atrophy and number of infarcts. Incident
      stroke and dementia only slightly modified this effect. CONCLUSION: The three
      year results of the LADIS study suggest that in older adults who seek medical
      attention for non-disabling complaints, severe age related changes in white
      matter independently and strongly predict rapid global functional decline.

PMID- 19581322
TI  - Procoagulant behavior and platelet microparticle generation on nanoporous
      alumina.
AB  - In the present work, we have investigated platelet microparticle (PMP) generation
      in whole blood after contact with nanoporous alumina. Alumina membranes with pore
      sizes of 20 and 200 nm in diameter were incubated with whole blood and the number
      of PMP in the fluid phase was determined by flow cytometry. The role of the
      complement system in PMP generation was investigated using an analog of the
      potent complement inhibitor compstatin. Moreover, the procoagulant activity of
      the two pore size membranes were compared by measuring thrombin formation.
      Results indicated that PMP were not present in the fluid phase after whole blood
      contact with either of the alumina membranes. However, scanning electron
      microscope micrographs clearly showed the presence of PMP clusters on the 200 nm
      pore size alumina, while PMP were practically absent on the 20 nm membrane. We
      probed no influence of complement activation in PMP generation and adhesion and
      we hypothesize that other specific material-related protein-platelet interactions
      are taking place. A clear difference in procoagulant activity between the
      membranes could also be seen, 20 nm alumina showed 100% higher procoagulant
      activity than 200 nm membrane. By combining surface evaluation and flow cytometry
      analyses of the fluid phase, we are able to conclude that 200 nm pore size
      alumina promotes PMP generation and adhesion while the 20 nm membrane does not
      appreciably cause any release or adhesion of PMP, thus indicating a direct
      connection between PMP generation and nanoporosity.

PMID- 19581323
TI  - Histological and radiographic evaluations of demineralized bone matrix and
      coralline hydroxyapatite in the rabbit tibia.
AB  - Complex fractures resulting in bone loss or impaired fracture healing remain
      problematic in trauma and orthopedic surgeries. Many bone graft substitutes have
      been developed and are commercially available. These products differ in their
      osteoconductive and osteoinductive properties. Differential enhancement of these
      properties may optimize the performance of these products for various orthopedic
      and craniofacial applications. The use of bone graft substitutes offers the
      ability to lessen the possible morbidity of the harvest site in autografts. The
      objective of the present study was to compare the ability of two bone graft
      substitutes, BioSet RT, an allograft demineralized bone matrix formulation, and
      ProOsteon 500R, a coralline hydroxyapatite, in a rabbit critical tibial defect
      model. BioSet RT and ProOsteon 500R were implanted into a unicortical proximal
      metaphyseal tibial defect and evaluated for new bone formation. Samples were
      analyzed radiographically and histologically at 1 day, 6 weeks, 12 weeks, and 24
      weeks post surgery. Both materials were biocompatible and demonstrated
      significant bone growth and remodeling. At 12 weeks, the BioSet RT implanted
      sites demonstrated significantly more defect closure and bone remodeling as
      determined by radiographic analyses with 10 out of 14 defects being completely
      healed versus 1 out of 14 being completely healed in the ProOsteon 500R implanted
      sites. At 24 weeks, both materials demonstrated complete closure of the defect as
      determined histologically. There were no statistical differences in radiographic
      scores between the two implanted materials. However, there was an observable
      trend that the BioSet RT material generated higher histological and radiographic
      scores, although not statistically significant. This study provides evidence that
      both BioSet RT and ProOsteon 500R are biocompatible and able to induce new bone
      formation as measured in this rabbit model. In addition, this in vivo study
      demonstrates the ability of BioSet RT to induce new bone formation in a shorter
      timeframe than ProOsteon 500R.

PMID- 19581324
TI  - Cell-free fetal DNA and RNA in maternal blood: implications for safer antenatal
      testing.

PMID- 19581325
TI  - Commentary: No risk, no objections? Ethical pitfalls of cell-free fetal DNA and
      RNA testing.

PMID- 19581326
TI  - Rwanda denies plan to forcibly sterilise people with learning difficulties.

PMID- 19581327
TI  - Ovarian cancer. Not a silent killer.

PMID- 19581328
TI  - Video tool in dementia. Ethical concerns.

PMID- 19581329
TI  - Institutional safety problem. Where is the NHS Macpherson?

PMID- 19581330
TI  - Palivizumab. An example of indication creep.

PMID- 19581332
TI  - Canada has world's highest rate of confirmed cases of A/H1N1, with Aboriginal
      people hardest hit.

PMID- 19581334
TI  - A novel role for uric acid in acute kidney injury associated with tumour lysis
      syndrome.

PMID- 19581336
TI  - Review of the evidence for a colorectal cancer screening programme in elderly
      people.
AB  - Colorectal cancer is a major public health issue, contributing to 16,000 UK
      deaths per year, most of these in the elderly population. A new NHS screening
      programme for colorectal cancer in people over 60 is being introduced across the
      country throughout 2009. The aim of this research was to review the current
      literature on colorectal cancer screening and determine how much of the evidence
      for screening is applicable to elderly people. MEDLINE database was searched for
      articles published between 1990 and 2007, using search terms of colorectal
      neoplasms, mass-screening, faecal occult blood, colonoscopy and sigmoidoscopy.
      Articles for inclusion were limited to those in English and those including older
      adults. The results showed that evidence for colorectal cancer screening in
      general has been well researched. However, little was found specifically on
      screening for elderly people, or looking at the different benefits and
      limitations in older people compared to younger people. Very few health agencies
      suggested an upper age limit for screening. In conclusion, there is very little
      research on screening for colorectal cancer specifically in elderly people,
      although many health authorities advise such screening. The health needs of an
      older population are different to those of middle-aged people and at present the
      screening programmes do not appear to reflect this.

PMID- 19581335
TI  - Mutational analysis of SAL-Like 4 (SALL4) in Han Chinese women with premature
      ovarian failure.
AB  - Pluripotency associated transcription factor, SAL-Like 4 (SALL4), might play an
      important role in conferring totipotency on oocytes. In the present study, we
      screened SALL4 coding regions for mutations in 100 Han Chinese women with non
      syndromic ovarian failure and discovered two novel non-synonymous variants in the
      SALL4 gene: c.541G>A (p.Val181Met) and c.2449A>G. (p.Thr817Ala). The former
      variant was located in an evolutionary conserved region of SALL4 protein and
      might affect its function. This is the first report to suggest that SALL4 might
      be a potential candidate gene of premature ovarian failure.

PMID- 19581337
TI  - Amyloid fibril length distribution quantified by atomic force microscopy single
      particle image analysis.
AB  - Amyloid fibrils are proteinaceous nano-scale linear aggregates. They are of key
      interest not only because of their association with numerous disorders, such as
      type II diabetes mellitus, Alzheimer's and Parkinson's diseases, but also because
      of their potential to become engineered high-performance nano-materials. Methods
      to characterise the length distribution of nano-scale linear aggregates such as
      amyloid fibrils are of paramount importance both in understanding the biological
      impact of these aggregates and in controlling their mechanical properties as
      potential nano-materials. Here, we present a new quantitative approach to the
      determination of the length distribution of amyloid fibrils using tapping-mode
      atomic force microscopy. The method described employs single-particle image
      analysis corrected for the length-dependent bias that is a common problem
      associated with surface-based imaging techniques. Applying this method, we
      provide a detailed characterisation of the length distribution of samples
      containing long-straight fibrils formed in vitro from beta(2)-microglobulin. The
      results suggest that the Weibull distribution is a suitable model in describing
      fibril length distributions, and reveal that fibril fragmentation is an important
      process even under unagitated conditions. These results demonstrate the
      significance of quantitative length distribution measurements in providing
      important new information regarding amyloid assembly.

PMID- 19581338
TI  - Clinical findings and recommendations made during home visits by a palliative
      care specialist physician.
AB  - Little has been reported regarding the nature of home visits by palliative care
      specialist physicians to assist in the management of complex cases. We determined
      the characteristics, actionable clinical findings and recommendations made during
      consecutive home visits conducted by a specialist physician for patients
      registered with a community palliative care service. Patient demographic
      information and clinical records were reviewed. Ninety-one patients received a
      total of 104 home and residential facility visits. Median patient age was 59 (Q1
      Q3, 43-72). Ten children (under the age of 14) received a total of 15 visits.
      Seventy-three patients (80%) had a cancer diagnosis. Median visit duration was 60
      min (Q1-Q3, 45-60). The major actionable clinical findings were pain (120),
      gastrointestinal (115), neuropsychiatric (58), mouth and skin (33) and
      respiratory (29). One-third of recommendations involved changes in analgesia
      regimen (opioids 67, adjuvants 44). The specialist physician home visit resulted
      in multiple patient care recommendations. This information may help palliative
      care programmes improve their care for patients and families in the community.

PMID- 19581339
TI  - Inter-laboratory evaluation of the bioluminescent Salmonella reverse mutation
      assay using 10 model chemicals.
AB  - We have developed the bioluminescent Salmonella reverse mutation assay as a tool
      for detecting mutagenicity applicable for high-throughput screening of new
      chemicals. In this study, we report the inter-laboratory evaluation of the assay
      using 10 model chemicals in five independent laboratories located in the USA
      (Groton, CT; Cambridge, MA and La Jolla, CA), Europe (Sandwich, Kent, UK) and
      Asia (Nagoya, Japan). The studies were performed in blinded fashion in all sites
      except for Groton and Cambridge laboratories. The chemicals were tested in at
      least three independent experiments using strains TA98-lux and TA100-lux in the
      presence and absence of metabolic activation. The results were statistically
      evaluated and compared to published results. Seven of the 10 compounds were
      positive in either TA98-lux and/or TA100-lux in the presence or absence of
      metabolic activation. The positive compound set included: nitrofurazone, 3-3'
      dimethoxybenzidine, benzo[a]pyrene, 1,4-benzoquinone dioxime, 2-amino-5
      nitrophenol, 2-bromo-4,6-dinitroaniline and busulfan. The remaining three
      compounds, namely, anthracene, crystal violet and benzyl chloride were negative
      in both Salmonella strains. Final results for individual compounds yielded 100%
      agreement among the laboratories and published data. Detailed comparison of all
      40 individual test conditions yielded 93% (37 of 40) agreement among
      participating laboratories. We conclude that the bioluminescent Salmonella
      reverse mutation assay is a robust, accurate and economical higher throughput
      assay applicable for the mutagenicity screening of chemicals.

PMID- 19581340
TI  - Susceptibility-weighted imaging in the diagnosis of early basal ganglia
      germinoma.
AB  - BACKGROUND AND PURPOSE: Germinomas originating from the basal ganglia (BG) are
      rare. Early diagnosis is important for favorable prognosis, but it is difficult
      due to the slow clinical course and subtle changes on neuroimaging. The purpose
      of this study was to evaluate the usefulness of susceptibility-weighted imaging
      (SWI) in the diagnosis of early BG germinoma. MATERIALS AND METHODS: From 2006 to
      2008, 6 BG germinomas were diagnosed in children at our institution by pathology.
      Conventional MR imaging and SWI were available in all cases. Clinical,
      neuroradiologic, and follow-up features were retrospectively studied. RESULTS:
      Three cases were classified as early BG germinomas. Conventional MR imaging
      demonstrated that the tumor size was <10 mm in the largest diameter. The tumors
      were invisible or showed slight hyperintensity on T1-weighted images (T1WI) and
      patchy slight hyperintensity on T2-weighted images (T2WI) without mass effect or
      enhancement. On SWI, the tumors appeared as obvious hypointensity in the globus
      pallidus and putamen, and the size was larger than that on conventional T1WI and
      T2WI. The other 3 cases with tumor size >10 mm in largest diameter were
      classified as late BG germinomas, with tumor necrosis, fluid-fluid levels, and
      perifocal edema, including 1 case with subependymal spread. On SWI, only the
      solid portion of the tumors showed hypointensity. No recurrence was noted on
      follow-up. CONCLUSIONS: SWI appears to be more sensitive in detecting early BG
      germinomas than conventional MR imaging. This capability may prove to be useful
      in future attempts to characterize early BG germinomas.

PMID- 19581341
TI  - What cycles the cell? -Robust autonomous cell cycle models.
AB  - The cell cycle is one of the best studied cellular mechanisms at the experimental
      and theoretical levels. Although most of the important biochemical components and
      reactions of the cell cycle are probably known, the precise way the cell cycle
      dynamics are driven is still under debate. This phenomenon is not atypical to
      many other biological systems where the knowledge of the molecular building
      blocks and the interactions between them does not lead to a coherent picture of
      the appropriate dynamics. We here propose a methodology to develop plausible
      models for the driving mechanisms of embryonic and cancerous cell cycles. We
      first define a key property of the system (a cyclic behaviour in the case of the
      embryonic cell cycle) and set mathematical constraints on the types of two
      variable simplified systems robustly reproducing such a cyclic behaviour. We then
      expand these robust systems to three variables and reiterate the procedure. At
      each step, we further limit the type of expanded systems to fit the known
      microbiology until a detailed description of the system is obtained. This
      methodology produces mathematical descriptions of the required biological systems
      that are more robust to changes in the precise function and rate constants. This
      methodology can be extended to practically any type of subcellular mechanism.

PMID- 19581342
TI  - A continuum model for the development of tissue-engineered cartilage around a
      chondrocyte.
AB  - The limited ability of cartilage to repair when damaged has led to the
      investigation of tissue engineering as a method for reconstructing cartilage. We
      propose a continuum multispecies model for the development of cartilage around a
      single chondrocyte. As in healthy cartilage, the model predicts a balance between
      synthesis, transport, binding and decay of matrix components. Two mechanisms are
      investigated for the transport of soluble matrix components: diffusion and
      advection, caused by displacement of the scaffold medium. Numerical results
      indicate that a parameter defined by the ratio of the flux of soluble components
      out of the chondrocyte and its diffusive flux determines which of these
      mechanisms is dominant. We investigate the diffusion-dominated and advection
      dominated limiting cases using perturbation analysis. Using parameter values from
      the literature, our modelling results suggest that both diffusion and advection
      are significant mechanisms in developing cartilage. Moreover, in this parameter
      regime, results are particularly sensitive to parameter values. These two
      observations could explain differences observed experimentally between various
      scaffold media. Modelling results are also used to predict the minimum
      chondrocyte seeding density required to produce functional cartilage.

PMID- 19581343
TI  - Apparent extinction or insufficient sampling?: comment on 'Deforestation and
      apparent extinctions of endemic forest beetles in Madagascar'.

PMID- 19581344
TI  - Deforestation and tropical insect extinctions.

PMID- 19581345
TI  - Letter to the editor.

PMID- 19581346
TI  - Role of NKX2-1 in N-bis(2-hydroxypropyl)-nitrosamine-induced thyroid adenoma in
      mice.
AB  - NKX2-1 is a homeodomain transcription factor that is critical for genesis of the
      thyroid and transcription of the thyroid-specific genes. Nkx2-1-thyroid
      conditional hypomorphic mice were previously developed in which Nkx2-1 gene
      expression is lost in 50% of the thyroid cells. Using this mouse line as compared
      with wild-type and Nkx2-1 heterozygous mice, a thyroid carcinogenesis study was
      carried out using the genotoxic carcinogen N-bis(2-hydroxypropyl)-nitrosamine
      (DHPN), followed by sulfadimethoxine (SDM) or the non-genotoxic carcinogen
      amitrole (3-amino-1,2,4-triazole). A significantly higher incidence of adenomas
      was obtained in Nkx2-1-thyroid-conditional hypomorphic mice as compared with the
      other two groups of mice only when they were treated with DHPN + SDM, but not
      amitrole. A bromodeoxyuridine incorporation study revealed that thyroids of the
      Nkx2-1-thyroid-conditional hypomorphic mice had >2-fold higher constitutive cell
      proliferation rate than the other two groups of mice, suggesting that this may be
      at least partially responsible for the increased incidence of adenoma in this
      mouse line after genotoxic carcinogen exposure. Thus, NKX2-1 may function to
      control the proliferation of thyroid follicular cells following damage by a
      genotoxic carcinogen.

PMID- 19581347
TI  - Identification of candidate genes affecting Delta9-tetrahydrocannabinol
      biosynthesis in Cannabis sativa.
AB  - RNA isolated from the glands of a Delta(9)-tetrahydrocannabinolic acid (THCA)
      producing strain of Cannabis sativa was used to generate a cDNA library
      containing over 100 000 expressed sequence tags (ESTs). Sequencing of over 2000
      clones from the library resulted in the identification of over 1000 unigenes.
      Candidate genes for almost every step in the biochemical pathways leading from
      primary metabolites to THCA were identified. Quantitative PCR analysis suggested
      that many of the pathway genes are preferentially expressed in the glands.
      Hexanoyl-CoA, one of the metabolites required for THCA synthesis, could be made
      via either de novo fatty acids synthesis or via the breakdown of existing lipids.
      qPCR analysis supported the de novo pathway. Many of the ESTs encode
      transcription factors and two putative MYB genes were identified that were
      preferentially expressed in glands. Given the similarity of the Cannabis MYB
      genes to those in other species with known functions, these Cannabis MYBs may
      play roles in regulating gland development and THCA synthesis. Three candidates
      for the polyketide synthase (PKS) gene responsible for the first committed step
      in the pathway to THCA were characterized in more detail. One of these was
      identical to a previously reported chalcone synthase (CHS) and was found to have
      CHS activity. All three could use malonyl-CoA and hexanoyl-CoA as substrates,
      including the CHS, but reaction conditions were not identified that allowed for
      the production of olivetolic acid (the proposed product of the PKS activity
      needed for THCA synthesis). One of the PKS candidates was highly and specifically
      expressed in glands (relative to whole leaves) and, on the basis of these
      expression data, it is proposed to be the most likely PKS responsible for
      olivetolic acid synthesis in Cannabis glands.

PMID- 19581348
TI  - Methods for incorporating the hypermutability of CpG dinucleotides in detecting
      natural selection operating at the amino acid sequence level.
AB  - In detecting natural selection operating at the amino acid sequence level by
      comparing the rates of synonymous (r(S)) and nonsynonymous (r(N)) substitutions,
      the rates of synonymous and nonsynonymous mutations are assumed to be
      approximately the same. In reality, however, these rates may not be the same if
      different proportions of synonymous and nonsynonymous sites overlap with CpG
      dinucleotides, which are known to be hypermutable in some organisms. Here, we
      develop the evolutionary pathway methods for comparing r(S) and r(N) at multiple
      codon sites (all-sites analysis) and at single codon sites (single-site analysis)
      that take into account the hypermutability at CpG dinucleotides in estimating the
      number of synonymous substitutions per synonymous site (d(S)) and nonsynonymous
      substitutions per nonsynonymous site (d(N)). Computer simulations show that the
      direction and magnitude of the bias in the estimation of d(N)/d(S) caused by the
      hypermutability of CpGs are determined by both the number of CpGs and the
      relative proportions of synonymous and nonsynonymous sites overlapping with CpGs.
      This bias is greatly reduced when using the methods we propose to account for the
      hypermutability of CpG dinucleotides. In an all-sites analysis of protamine 1
      genes from primates, d(N)/d(S) > 1 was observed for many pairs if the
      hypermutability was ignored. However, d(N)/d(S) becomes <or=1 for most of these
      pairs when the CpG sites are assumed to be hypermutable. Therefore, statistical
      indications of positive selection in some sequences or individual codons may be
      caused by mutation rate differences in synonymous and nonsynonymous sites.

PMID- 19581349
TI  - Respiratory function in patients with stable anorexia nervosa.
AB  - BACKGROUND: The impact of undernutrition on lung physiology and respiratory
      muscle performance is still incompletely investigated. The purpose of this study
      was to assess the functional consequences of malnutrition on the respiratory
      system in stable patients with anorexia nervosa (AN). METHODS: Pulmonary function
      tests, maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax),
      and the parameters of control of breathing were obtained in 27 patients with AN
      (mean [+/- SD] age, 24 +/- 7 years; BMI, 16 +/- 1 kg/m(2); duration of disease, 6
      +/- 6 years) and in a group of matched healthy subjects. RESULTS: Compared with
      control subjects, significant reductions in the diffusing capacity of the lung
      for carbon monoxide (Dlco) and lung diffusion capacity corrected for alveolar
      ventilation (p < 0.001), which progressively worsened with the duration of
      disease, were found in the AN group. Only the membrane diffusing capacity was
      reduced in patients with AN (p < 0.05), while pulmonary capillary blood volume
      was similar to that of control subjects. Lung density measurements based on CT
      scan analysis were normal in a subgroup of eight patients with AN with low Dlco.
      Both Pimax and Pemax were decreased in patients with AN (p < 0.001), but the mild
      to-moderate impairment to generate force of the respiratory muscles did not
      progress with time. In these patients with AN, the parameters of control of
      breathing were in the normal range and were comparable to those of control
      subjects. CONCLUSIONS: The functional alterations found in patients with AN
      indicate the presence of the progressive enlargement of peripheral lung units
      without relevant alveolar septa destruction. In the first 3 years of disease,
      appreciable weakness of respiratory muscles develops in patients with stable AN
      without further impairment over time.

PMID- 19581350
TI  - Measurement of dynamic hyperinflation after a 6-minute walk test in patients with
      COPD.
AB  - BACKGROUND: Dynamic hyperinflation (DH) develops in patients with COPD during
      incremental exercise with a cycle ergometer. The aims of this study were to
      determine whether DH can be evidenced after walking with a handheld spirometer
      and to determine its functional consequences. METHODS: Fifty patients with COPD
      (39 men; median age, 60 years [interquartile range (IQR), 54 to 69 years];
      FEV(1), 45% predicted [IQR, 31 to 67% predicted]) underwent pulmonary function
      tests and a 6-min walk test (6MWT). Inspiratory capacity (IC) was measured with
      the patient in the standing position at rest and immediately after the 6MWT with
      a portable spirometer. Dyspnea was evaluated directly (change in Borg score
      during 6MWT) and indirectly (Medical Research Council scale). The first 20
      patients performed an incremental exercise test with cycle ergometer that allowed
      for the measurement of IC at peak exercise and repeatedly during the first 3 min
      of recovery. RESULTS: The median change in IC during the 6MWT was -210 mL (IQR,
      55 to -440; n = 50), whereas the median change in IC during the exercise test was
      -295 mL (IQR, -145 to -515; n = 20). Both the IC and IC changes after 6MWT
      correlated to values after the exercise test. DH decreased rapidly after the end
      of the exercise test but was nonsignificantly different from the baseline value
      after 75 s of recovery. The percentage of decrease in IC during the 6MWT
      correlated with dyspnea (change in Borg score during 6MWT: r(2) = 0.21; p =
      0.0006). CONCLUSIONS: DH can be measured during a 6MWT with a handheld spirometer
      to allow for its evaluation in daily practice and its contribution to dyspnea
      while walking.

PMID- 19581351
TI  - Clinical differences between interstitial lung disease associated with clinically
      amyopathic dermatomyositis and classic dermatomyositis.
AB  - BACKGROUND: Interstitial lung disease (ILD) associated with clinically amyopathic
      dermatomyositis (CADM) is a potentially fatal condition in which the clinical
      features are not well understood. The aim of the present study was to clarify the
      differences in clinical characteristics and prognosis of patients with ILD
      associated with CADM (CADM-ILD) and classic dermatomyositis associated with ILD
      (DM-ILD). METHODS: We retrospectively studied consecutive patients with CADM-ILD
      and classic DM-ILD who were hospitalized between 2001 and 2007 at Nagasaki
      University Hospital. The study group consisted of 11 patients with CADM-ILD and
      16 patients with classic DM-ILD. We compared the clinical features and prognosis
      between the two forms. RESULTS: The Pao(2)/Fio(2) ratio was significantly lower
      in patients with CADM-ILD than in patients with classic DM-ILD. The lymphocyte
      subsets ratio in the BAL fluid of patients with CADM-ILD was significantly higher
      than the corresponding ratio in patients with classic DM-ILD. ILD is classified
      as acute or chronic, and the acute subtype was more common in patients with CADM
      ILD than in those with classic DM-ILD. The mortality rate for patients with CADM
      ILD (45%) was much higher than that for patients with classic DM-ILD (6%), and
      all of the CADM deaths occurred in the group of patients with acute CADM-ILD.
      CONCLUSION: Our data suggest that the higher prevalence of the acute subtype of
      ILD in patients with CADM results in a higher mortality rate for patients with
      CADM-ILD.

PMID- 19581352
TI  - Pleural effusions following cardiac surgery: prevalence, risk factors, and
      clinical features.
AB  - BACKGROUND: Pleural effusion is a common complication of cardiac surgery, but its
      characteristics and predisposing factors should be documented further. Our
      objective was to determine the prevalence, characteristics, and determinants of
      clinically significant pleural effusions, defined as those requiring therapeutic
      pleural drainage according to clinical assessment. METHODS: The prevalence and
      characteristics of patients who had a pleural effusion within 30 days of
      undergoing coronary artery bypass graft, valve replacement, or both were analyzed
      retrospectively at our institution over a 2-year period. RESULTS: Among the 2,892
      patients included in the study (mean age, 66 years; men, 2,139), 192 patients
      (6.6%) had experienced a clinically significant pleural effusion in the 30 days
      postsurgery. These effusions occurred after a mean (+/- SD) duration of 6.6 +/-
      5.9 days following interventions. Pleural fluid analysis was obtained in 114
      patients (59.4%); all met the criteria for an exudate. Pleural fluid was
      hemorrhagic in 50% of cases. Age, body weight, baseline pulmonary function, and
      smoking status were similar between patients with and without effusion; however,
      the proportion of women; the number of patients with previous conditions of heart
      failure, atrial fibrillation, or peripheral vascular disease; and the number of
      patients receiving therapy with an anticoagulant or antiarrhythmic agent was
      higher in the pleural effusion group. Patients with pleural effusion had an
      increased prevalence of postoperative complications. CONCLUSIONS: Pleural
      effusion is a common complication of heart surgery, is associated with other
      postoperative complications, and is more frequent in women and in patients with
      associated cardiac or vascular comorbidities and medications used to treat those
      conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00665015.

PMID- 19581354
TI  - 5-year lung cancer screening experience: growth curves of 18 lung cancers
      compared to histologic type, CT attenuation, stage, survival, and size.
AB  - BACKGROUND: Although no study has prospectively documented the rate at which lung
      cancers grow, many have assumed exponential growth. The purpose of this study was
      to document the growth of lung cancers detected in high-risk participants
      receiving annual screening chest CT scans. METHODS: Eighteen lung cancers were
      evaluated by at least four serial CT scans (4 men, 14 women; age range, 53 to 79
      years; mean age, 66 years). CT scans were retrospectively reviewed for
      appearance, size, and volume (volume [v] = pi/6[ab(2)]). Growth curves (x = time
      [in days]; y = volume [cubic millimeters]) were plotted and subcategorized by
      histology, CT scan attenuation, stage, survival, and initial size. RESULTS:
      Inclusion criteria favored smaller, less aggressive cancers. Growth curves
      varied, even when subcategorized by histology, CT scan attenuation, stage,
      survival, or initial size. Cancers associated with higher stages, mortality, or
      recurrence showed fairly steady growth or accelerated growth compared with
      earlier growth, although these growth patterns also were seen in lesser-stage
      lung cancers. Most lung cancers enlarged at fairly steady increments, but several
      demonstrated fairly flat growth curves, and others demonstrated periods of
      accelerated growth. CONCLUSIONS: This study is the first to plot individual lung
      cancer growth curves. Although parameters favored smaller, less aggressive
      cancers in women, it showed that lung cancers are not limited to exponential
      growth. Tumor size at one point or growth between two points did not appear to
      predict future growth. Studies and equations assuming exponential growth may
      potentially misrepresent an indeterminate nodule or the aggressiveness of a lung
      cancer.

PMID- 19581353
TI  - Prevalence and progression of osteoporosis in patients with COPD: results from
      the TOwards a Revolution in COPD Health study.
AB  - BACKGROUND: Osteoporosis is common in patients with COPD, but its prevalence and
      progression are not well characterized. Concerns have been raised over the
      possible deleterious effect of long-term therapy with inhaled corticosteroids
      (ICSs) on bone density in this population. Here, we investigated the long-term
      effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL)
      alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone
      fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in
      COPD Health (TORCH) study. METHODS: A randomized, double-blind, parallel-group,
      placebo-controlled study conducted at 88 US centers involving 658 patients (a
      subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50
      microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was
      administered for 3 years. Baseline and yearly measurements of BMD at the hip and
      lumbar spine were performed. The incidence of traumatic and nontraumatic bone
      fractures was recorded. RESULTS: At baseline, 18% of men and 30% of women had
      osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD
      assessments. Forty-three percent of subjects completed all testing. The changes
      in BMD at the hip and lumbar spine over 3 years were small. No significant
      differences were observed between treatment arms (adjusted mean percent change
      from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and 
      3.2% for SFC therapy, respectively; while, the corresponding changes for the
      lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP,
      and SFC therapy). The incidence of fractures was low and was similar for all
      treatments (5.1% to 6.3%). CONCLUSIONS: Osteoporosis is highly prevalent in
      patients with COPD, irrespective of gender. In the TORCH study, no significant
      effect on BMD was detected for ICS therapy compared with placebo. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NTC00268216.

PMID- 19581355
TI  - Childhood respiratory illness and lung function at ages 14 and 50 years:
      childhood respiratory illness and lung function.
AB  - BACKGROUND: Although childhood respiratory tract infections and low birth weight
      have both been associated with reduced adult lung function, little is known about
      the timing of these associations during life. We used data from the Newcastle
      Thousand Families Study to examine how these and other factors influenced FEV(1)
      at age 14 years and between 14 and 49 to 51 years. METHODS: Detailed information
      was collected prospectively during childhood. At age 14 years, 252 members of the
      cohort were recruited into a case-control study of respiratory health, which
      included measurement of FEV(1). One hundred twenty-two of these were measured
      again at age 49 to 51 years. Linear regression models were used to examine cross
      sectional and longitudinal influences on FEV(1). RESULTS: Lower height (P <
      .001), lower BMI (P < .001), being breast fed for less than 4 weeks (P = .028),
      childhood history of severe respiratory illness (P = .014), childhood history of
      asthma (P = .004), childhood history of TB (P = .023), and birth into a lower
      social class (P = .049) were all significant independent predictors of lower
      FEV(1) at 14 years of age. Correspondingly, being a women (P < .001), and having
      a higher FEV(1) at age 14 years (P < .001), a lower standardized birth weight (P
      = .025), a greater lifetime number of cigarettes smoked (P = .007), and a
      childhood history of severe respiratory illness (P = .047) were all independently
      associated with a greater decline (or a smaller increase) in FEV(1) between age
      14 and 49 to 51 years. CONCLUSIONS: This study suggests that the change in FEV(1)
      between youth and middle age depends on several factors acting throughout life,
      including FEV(1) in adolescence, sex, cigarette smoking, birth weight, and
      childhood respiratory health.

PMID- 19581357
TI  - Lost in laterality: interpreting ''preferred side of the head during mobile phone
      use and risk of brain tumour'' associations.
AB  - Due to the highly localized exposure from mobile phones, the preferred side of
      the head during their use is important information when investigating a possible
      link with brain tumour risk, but at the same time, error and bias hamper the
      assessment of this information in case-control studies. Current studies provide
      evidence of reporting bias insofar as cases appear to over-report the side of the
      head where the tumour occurred as the one that they preferred in the past when
      using mobile phones. More refined methods of analysis among only cases or
      prospective studies with an assessment of the laterality of mobile phone use
      before the diagnosis of disease are needed to evaluate whether associations seen
      in some studies are entirely due to reporting bias or a mixture of reporting bias
      and a causal effect.

PMID- 19581358
TI  - Cross-national comparisons of non-harmonized indicators may lead to more
      confusion than clarification.
AB  - AIMS: A newly published study showed that the life expectancy for Danes was below
      the European Union (EU) average. Furthermore, the study showed that healthy life
      years (HLYs) at 50 years of age were much higher in Denmark than in the other EU
      countries in 2005. However, the results of this study should be interpreted with
      caution. METHODS: The analyses regarding HLYs were based on the global long-term
      activity limitation index as a measure of disability and were included in the EU
      Survey on Income and Living Condition (EU-SILC). In Denmark two response
      categories were used to asses long-term activity limitation (yes; no) compared to
      three levels in all other countries (severely limited; limited but not severely;
      none). In addition, the wording of the question in Denmark makes cross-national
      comparisons even more inadequate. The questions and the response categories were
      revised in the Danish SILC-2008. RESULTS: A comparison of the previous and the
      revised indicator shows that the estimated number of HLYs at 50 years of age is
      approximately three years lower for both men and women in 2008 than in 2005.
      Furthermore, in Denmark data was collected via telephone interviews or postal
      questionnaires. However, in almost all other countries data was collected via
      face-to-face interviews. It is well known that the mode of data collection may
      affect response distributions. CONCLUSIONS: Results based on non-harmonized
      indicators should always be interpreted cautiously to avoid policy-makers and
      others reaching erroneous conclusions.

PMID- 19581356
TI  - Criteria to screen for chronic sinonasal disease.
AB  - BACKGROUND: Sinusitis and rhinitis are associated with uncontrolled asthma. There
      are no simple, validated tools to screen for these diseases. The objective of
      this study was to assess instruments to assist in the diagnosis of chronic
      sinonasal disease. METHODS: Participants without acute sinonasal symptoms
      underwent an extensive evaluation. The results were submitted to an expert panel
      that used the Delphi method to achieve consensus. Using the consensus diagnosis
      of the panel, we determined the sensitivity and specificity of test procedures to
      diagnose chronic sinonasal disease. We determined the reproducibility of the most
      sensitive and specific instrument in a separate cohort. RESULTS: Fifty-nine
      participants were evaluated, and the expert panel reached consensus for all (42
      participants with chronic sinonasal disease, 17 participants without chronic
      sinonasal disease). A six-item questionnaire based on the frequency of nasal
      symptoms was the most sensitive tool used to diagnose sinonasal disease (minimum
      specificity, 0.90). Reproducibility testing in a separate cohort of 63
      participants (41 chronic sinonasal disease with asthma, 22 chronic sinonasal
      disease without asthma) showed a concordance correlation coefficient of 0.91 (95%
      CI, 0.85 to 0.94) when this questionnaire was limited to five items (ie,
      excluding a question on smell). This five-item questionnaire had a sensitivity of
      0.90 (95% CI, 0.77 to 0.97), a specificity of 0.94 (95% CI, 0.71 to 1.00), and an
      area under the receiver operating characteristic curve of 0.97 (95% CI, 0.93 to
      1.0). Sinus CT scans and nasal endoscopy lacked sensitivity for use in the
      diagnosis of chronic sinonasal disease. CONCLUSIONS: We have developed a
      sensitive, specific, and reproducible instrument to screen for chronic sinonasal
      disease. Validation studies of this five-item questionnaire are needed, including
      in patients with asthma.

PMID- 19581359
TI  - Pneumococcal LytR, a protein from the LytR-CpsA-Psr family, is essential for
      normal septum formation in Streptococcus pneumoniae.
AB  - Proliferation of the human-pathogenic bacterium Streptococcus pneumoniae is
      fundamentally linked to the bacterial proteins that function in cell division.
      Here, we show that LytR, a pneumococcal protein from the LytR-CpsA-Psr family, is
      essential to this process.

PMID- 19581360
TI  - Staphylococcus aureus YoeB homologues inhibit translation initiation.
AB  - YoeB is a bacterial toxin encoded by the yefM-yoeB toxin-antitoxin system found
      in various bacterial genomes. Here, we show that Staphylococcus aureus contains
      two YoeB homologues, both of which function as ribosome-dependent mRNA
      interferases to inhibit translation initiation in a manner identical to that of
      YoeB-ec from Escherichia coli.

PMID- 19581361
TI  - The electron transfer system of syntrophically grown Desulfovibrio vulgaris.
AB  - Interspecies hydrogen transfer between organisms producing and consuming hydrogen
      promotes the decomposition of organic matter in most anoxic environments.
      Although syntrophic coupling between hydrogen producers and consumers is a major
      feature of the carbon cycle, mechanisms for energy recovery at the extremely low
      free energies of reactions typical of these anaerobic communities have not been
      established. In this study, comparative transcriptional analysis of a model
      sulfate-reducing microbe, Desulfovibrio vulgaris Hildenborough, suggested the use
      of alternative electron transfer systems dependent on growth modality. During
      syntrophic growth on lactate with a hydrogenotrophic methanogen, numerous genes
      involved in electron transfer and energy generation were upregulated in D.
      vulgaris compared with their expression in sulfate-limited monocultures. In
      particular, genes coding for the putative membrane-bound Coo hydrogenase, two
      periplasmic hydrogenases (Hyd and Hyn), and the well-characterized high-molecular
      weight cytochrome (Hmc) were among the most highly expressed and upregulated
      genes. Additionally, a predicted operon containing genes involved in lactate
      transport and oxidation exhibited upregulation, further suggesting an alternative
      pathway for electrons derived from lactate oxidation during syntrophic growth.
      Mutations in a subset of genes coding for Coo, Hmc, Hyd, and Hyn impaired or
      severely limited syntrophic growth but had little effect on growth via sulfate
      respiration. These results demonstrate that syntrophic growth and sulfate
      respiration use largely independent energy generation pathways and imply that to
      understand microbial processes that sustain nutrient cycling, lifestyles not
      captured in pure culture must be considered.

PMID- 19581362
TI  - The CheZ binding interface of CheAS is located in alpha-helix E.
AB  - Specific CheA-short (CheA(S)) residues, L123 and L126, were identified as
      critical for CheZ binding. In the CheA(S) 'P1-CheZ nuclear magnetic resonance
      structure, these residues form an interaction surface on alpha-helix E in the 'P1
      domain. Both L123 and L126 are buried in CheA-long (CheA(L)), providing an
      explanation for why CheA(L) fails to bind CheZ.

PMID- 19581363
TI  - Bifurcated degradative pathway of 3-sulfolactate in Roseovarius nubinhibens ISM
      via sulfoacetaldehyde acetyltransferase and (S)-cysteate sulfolyase.
AB  - Data from the genome sequence of the aerobic, marine bacterium Roseovarius
      nubinhibens ISM were interpreted such that 3-sulfolactate would be degraded as a
      sole source of carbon and energy for growth via a novel bifurcated pathway
      including two known desulfonative enzymes, sulfoacetaldehyde acetyltransferase
      (EC 2.3.3.15) (Xsc) and cysteate sulfo-lyase (EC 4.4.1.25) (CuyA). Strain ISM
      utilized sulfolactate quantitatively with stoichiometric excretion of the
      sulfonate sulfur as sulfate. A combination of enzyme assays, analytical
      chemistry, enzyme purification, peptide mass fingerprinting, and reverse
      transcription-PCR data supported the presence of an inducible, tripartite
      sulfolactate uptake system (SlcHFG), and a membrane-bound sulfolactate
      dehydrogenase (SlcD) which generated 3-sulfopyruvate, the point of bifurcation. 3
      Sulfopyruvate was in part decarboxylated by 3-sulfopyruvate decarboxylase (EC
      4.1.1.79) (ComDE), which was purified. The sulfoacetaldehyde that was formed was
      desulfonated by Xsc, which was identified, and the acetyl phosphate was converted
      to acetyl-coenzyme A by phosphate acetyltransferase (Pta). The other portion of
      the 3-sulfopyruvate was transaminated to (S)-cysteate, which was desulfonated by
      CuyA, which was identified. The sulfite that was formed was presumably exported
      by CuyZ (TC 9.B.7.1.1 in the transport classification system), and a periplasmic
      sulfite dehydrogenase is presumed. Bioinformatic analyses indicated that
      transporter SlcHFG is rare but that SlcD is involved in three different
      combinations of pathways, the bifurcated pathway shown here, via CuyA alone, and
      via Xsc alone. This novel pathway involves ComDE in biodegradation, whereas it
      was discovered in the biosynthesis of coenzyme M. The different pathways of
      desulfonation of sulfolactate presumably represent final steps in the
      biodegradation of sulfoquinovose (and exudates derived from it) in marine and
      aquatic environments.

PMID- 19581364
TI  - The germination-specific lytic enzymes SleB, CwlJ1, and CwlJ2 each contribute to
      Bacillus anthracis spore germination and virulence.
AB  - The bacterial spore cortex is critical for spore stability and dormancy and must
      be hydrolyzed by germination-specific lytic enzymes (GSLEs), which allows
      complete germination and vegetative cell outgrowth. We created in-frame deletions
      of three genes that encode GSLEs that have been shown to be active in Bacillus
      anthracis germination: sleB, cwlJ1, and cwlJ2. Phenotypic analysis of individual
      null mutations showed that the removal of any one of these genes was not
      sufficient to disrupt spore germination in nutrient-rich media. This finding
      indicates that these genes have partially redundant functions. Double and triple
      deletions of these genes resulted in more significant defects. Although a small
      subset of DeltasleB DeltacwlJ1 spores germinate with wild-type kinetics, for the
      overall population there is a 3-order-of-magnitude decrease in the colony-forming
      efficiency compared with wild-type spores. DeltasleB DeltacwlJ1 DeltacwlJ2 spores
      are unable to complete germination in nutrient-rich conditions in vitro. Both
      DeltasleB DeltacwlJ1 and DeltasleB DeltacwlJ1 DeltacwlJ2 spores are significantly
      attenuated, but are not completely devoid of virulence, in a mouse model of
      inhalation anthrax. Although unable to germinate in standard nutrient-rich media,
      spores lacking SleB, CwlJ1, and CwlJ2 are able to germinate in whole blood and
      serum in vitro, which may explain the persistent low levels of virulence observed
      in mouse infections. This work contributes to our understanding of GSLE
      activation and function during germination. This information may result in
      identification of useful therapeutic targets for the disease anthrax, as well as
      provide insights into ways to induce the breakdown of the protective cortex
      layer, facilitating easier decontamination of resistant spores.

PMID- 19581365
TI  - Characterization of the dicarboxylate transporter DctA in Corynebacterium
      glutamicum.
AB  - Transporters of the dicarboxylate amino acid-cation symporter family often
      mediate uptake of C(4)-dicarboxylates, such as succinate or l-malate, in
      bacteria. A member of this family, dicarboxylate transporter A (DctA) from
      Corynebacterium glutamicum, was characterized to catalyze uptake of the C(4)
      dicarboxylates succinate, fumarate, and l-malate, which was inhibited by
      oxaloacetate, 2-oxoglutarate, and glyoxylate. DctA activity was not affected by
      sodium availability but was dependent on the electrochemical proton potential.
      Efficient growth of C. glutamicum in minimal medium with succinate, fumarate, or
      l-malate as the sole carbon source required high dctA expression levels due
      either to a promoter-up mutation identified in a spontaneous mutant or to ectopic
      overexpression. Mutant analysis indicated that DctA and DccT, a C(4)
      dicarboxylate divalent anion/sodium symporter-type transporter, are the only
      transporters for succinate, fumarate, and l-malate in C. glutamicum.

PMID- 19581366
TI  - Structure of compositionally simple lipopolysaccharide from marine synechococcus.
AB  - Lipopolysaccharide (LPS) is the first defense against changing environmental
      factors for many bacteria. Here, we report the first structure of the LPS from
      cyanobacteria based on two strains of marine Synechococcus, WH8102 and CC9311.
      While enteric LPS contains some of the most complex carbohydrate residues in
      nature, the full-length versions of these cyanobacterial LPSs have neither
      heptose nor 3-deoxy-D-manno-octulosonic acid (Kdo) but instead 4-linked glucose
      as their main saccharide component, with low levels of glucosamine and
      galacturonic acid also present. Matrix-assisted laser desorption ionization mass
      spectrometry of the intact minimal core LPS reveals triacylated and tetraacylated
      structures having a heterogeneous mix of both hydroxylated and nonhydroxylated
      fatty acids connected to the diglucosamine backbone and a predominantly glucose
      outer core-like region for both strains. WH8102 incorporated rhamnose in this
      region as well, contributing to differences in sugar composition and possibly
      nutritional differences between the strains. In contrast to enteric lipid A,
      which can be liberated from LPS by mild acid hydrolysis, lipid A from these
      organisms could be produced by only two novel procedures: triethylamine-assisted
      periodate oxidation and acetolysis. The lipid A contains odd-chain hydroxylated
      fatty acids, lacks phosphate, and contains a single galacturonic acid. The LPS
      lacks any limulus amoebocyte lysate gelation activity. The highly simplified
      nature of LPSs from these organisms leads us to believe that they may represent
      either a primordial structure or an adaptation to the relatively higher salt and
      potentially growth-limiting phosphate levels in marine environments.

PMID- 19581367
TI  - Short-chain chromate ion transporter proteins from Bacillus subtilis confer
      chromate resistance in Escherichia coli.
AB  - Tandem paired genes encoding putative short-chain monodomain protein members of
      the chromate ion transporter (CHR) superfamily (ywrB and ywrA) were cloned from
      genomic DNA of Bacillus subtilis strain 168. The transcription of the paired
      genes, renamed chr3N and chr3C, respectively, was shown to occur via a
      bicistronic mRNA generated from a promoter upstream of the chr3N gene. The chr3N
      and chr3C genes conferred chromate resistance when expressed in Escherichia coli
      strain W3110. The cloned chr3N gene alone did not confer chromate resistance on
      E. coli, suggesting that both chr3N and chr3C genes are required for function. E.
      coli cells expressing paired chr3N and chr3C genes demonstrated diminished uptake
      of chromate compared to that by a vector-only control strain. These results
      suggest that short-chain CHR proteins form heterodimer transporters which efflux
      chromate ions from the cytoplasm.

PMID- 19581368
TI  - An A257V mutation in the bacillus subtilis response regulator Spo0A prevents
      regulated expression of promoters with low-consensus binding sites.
AB  - In Bacillus species, the master regulator of sporulation is Spo0A. Spo0A
      functions by both activating and repressing transcription initiation from target
      promoters that contain 0A boxes, the binding sites for Spo0A. Several classes of
      spo0A mutants have been isolated, and the molecular basis for their phenotypes
      has been determined. However, the molecular basis of the Spo0A(A257V)
      substitution, representative of an unusual phenotypic class, is not understood.
      Spo0A(A257V) is unusual in that it abolishes sporulation; in vivo, it fails to
      activate transcription from key stage II promoters yet retains the ability to
      repress the abrB promoter. To determine how Spo0A(A257V) retains the ability to
      repress but not stimulate transcription, we performed a series of in vitro and in
      vivo assays. We found unexpectedly that the mutant protein both stimulated
      transcription from the spoIIG promoter and repressed transcription from the abrB
      promoter, albeit twofold less than the wild type. A DNA binding analysis of
      Spo0A(A257V) showed that the mutant protein was less able to tolerate alterations
      in the sequence and arrangement of its DNA binding sites than the wild-type
      protein. In addition, we found that Spo0A(A257V) could stimulate transcription of
      a mutant spoIIG promoter in vivo in which low-consensus binding sites were
      replaced by high-consensus binding sites. We conclude that Spo0A(A257V) is able
      to bind to and regulate the expression of only genes whose promoters contain high
      consensus binding sites and that this effect is sufficient to explain the
      observed sporulation defect.

PMID- 19581369
TI  - In situ characterization of differences in the viscoelastic response of
      individual gram-negative and gram-positive bacterial cells.
AB  - We used a novel atomic force microscopy (AFM)-based technique to compare the
      local viscoelastic properties of individual gram-negative (Escherichia coli) and
      gram-positive (Bacillus subtilis) bacterial cells. We found that the viscoelastic
      properties of the bacterial cells are well described by a three-component
      mechanical model that combines an instantaneous elastic response and a delayed
      elastic response. These experiments have allowed us to investigate the
      relationship between the viscoelastic properties and the structure and
      composition of the cell envelope. In addition, this is the first report in which
      the mechanical role of Lpp, the major peptidoglycan-associated lipoprotein and
      one of the most abundant outer membrane proteins in E. coli cells, has been
      quantified. We expect that our findings will be helpful in increasing the
      understanding of the structure-property relationships of bacterial cell
      envelopes.

PMID- 19581370
TI  - The autolysin LytA contributes to efficient bacteriophage progeny release in
      Streptococcus pneumoniae.
AB  - Most bacteriophages (phages) release their progeny through the action of holins
      that form lesions in the cytoplasmic membrane and lysins that degrade the
      bacterial peptidoglycan. Although the function of each protein is well
      established in phages infecting Streptococcus pneumoniae, the role--if any--of
      the powerful bacterial autolysin LytA in virion release is currently unknown. In
      this study, deletions of the bacterial and phage lysins were done in lysogenic S.
      pneumoniae strains, allowing the evaluation of the contribution of each lytic
      enzyme to phage release through the monitoring of bacterial-culture lysis and
      phage plaque assays. In addition, we assessed membrane integrity during phage
      mediated lysis using flow cytometry to evaluate the regulatory role of holins
      over the lytic activities. Our data show that LytA is activated at the end of the
      lytic cycle and that its triggering results from holin-induced membrane
      permeabilization. In the absence of phage lysin, LytA is able to mediate
      bacterial lysis and phage release, although exclusive dependence on the autolysin
      results in reduced virion egress and altered kinetics that may impair phage
      fitness. Under normal conditions, activation of bacterial LytA, together with the
      phage lysin, leads to greater phage progeny release. Our findings demonstrate
      that S. pneumoniae phages use the ubiquitous host autolysin to accomplish an
      optimal phage exiting strategy.

PMID- 19581372
TI  - Are there lateral as well as polar engines for A-motile gliding in myxobacteria?

PMID- 19581371
TI  - Selection, recombination, and virulence gene diversity among group B
      streptococcal genotypes.
AB  - Transmission of group B Streptococcus (GBS) from mothers to neonates during
      childbirth is a leading cause of neonatal sepsis and meningitis. Although
      subtyping tools have identified specific GBS phylogenetic lineages that are
      important in neonatal disease, little is known about the genetic diversity of
      these lineages or the roles that recombination and selection play in the
      generation of emergent genotypes. Here, we examined genetic variation, selection,
      and recombination in seven multilocus sequence typing (MLST) loci from 94
      invasive, colonizing, and bovine strains representing 38 GBS sequence types and
      performed DNA sequencing and PCR-based restriction fragment length polymorphism
      analysis of several putative virulence genes to identify gene content differences
      between genotypes. Despite the low level of diversity in the MLST loci, a
      neighbor net analysis revealed a variable range of genetic exchange among the
      seven clonal complexes (CCs) identified, suggesting that recombination is partly
      responsible for the diversity observed between genotypes. Recombination is also
      important for several virulence genes, as some gene alleles had evidence for
      lateral gene exchange across divergent genotypes. The CC-17 lineage, which is
      associated with neonatal disease, is relatively homogeneous and therefore appears
      to have diverged independently with an exclusive set of virulence
      characteristics. These data suggest that different GBS genetic backgrounds have
      distinct virulence gene profiles that may be important for disease pathogenesis.
      Such profiles could be used as markers for the rapid detection of strains with an
      increased propensity to cause neonatal disease and may be considered useful
      vaccine targets.

PMID- 19581373
TI  - The role of circulating mesenchymal progenitor cells (fibrocytes) in the
      pathogenesis of pulmonary fibrosis.
AB  - Pulmonary fibrosis is associated with a number of disorders that affect the lung.
      Although there are several cellular types that are involved in the pathogenesis
      pulmonary fibrosis, the resident lung fibroblast has been viewed traditionally as
      the primary cell involved in promoting the deposition of ECM that culminates in
      pulmonary fibrosis. However, recent findings demonstrate that a circulating cell
      (i.e., the fibrocyte) can contribute to the evolution of pulmonary fibrosis.
      Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a
      variety of cell-surface markers related to leukocytes, hematopoietic progenitor
      cells, and fibroblasts. Fibrocytes are unique in that they are capable of
      differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In
      this review, we present data supporting the critical role these cells play in the
      pathogenesis of pulmonary fibrosis.

PMID- 19581374
TI  - Nucleophosmin may act as an alarmin: implications for severe sepsis.
AB  - NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis,
      centrosome duplication, cell-cycle progression, apoptosis, cell differentiation,
      and sensing cellular stress. Alarmins are endogenous molecules released from
      activated cells and/or dying cells, which activate the immune system and cause
      severe damage to cells and tissue organs. In the present work, stimulation of
      cells with the alarmin-inducible molecule endotoxin, for 16 h, resulted in NPM
      release into the culture supernatants of RAW264.7 cells, a murine macrophage cell
      line. Extracellular NPM was detected in the ascites of the CLP model. NPM was
      translocated into the cytoplasm from the nucleus in LPS -stimulated RAW264.7
      cells; furthermore, NPM was detected in the cytosols of infiltrated macrophages
      in the CLP model. rNPM induced release of proinflammatory cytokines, TNF-alpha,
      IL-6, and MCP-1, from RAW264.7 cells and increased the expression level of ICAM-1
      in HUVECs. NPM induced the phosphorylation of MAPKs in RAW264.7 cells. Our data
      indicate that NPM may have potent biological activities that contribute to
      systemic inflammation. Further investigations of the role of NPM may lead to new
      therapies for patients with septic shock or other inflammatory diseases.

PMID- 19581376
TI  - Trends in the incidence of sickness absence due to common mental disorders
      between 2001 and 2007 in the Netherlands.
AB  - BACKGROUND: Mental disorders are an important public health problem because of
      their prevalence and the probability of long-term work disability. The incidence
      of sickness absence with mental disorders has increased between 1985 and 2000,
      but little is known about trends in recent years. This study investigated the
      incidence of sickness absence due to common mental disorders in the Netherlands
      from 2001 to 2007. METHODS: Observational study in about 1 million employees,
      working in various economic sectors, representative for the Dutch workforce.
      Sickness absence episodes were medically certified by an occupational physician
      utmost in the fifth week of absence. The 12-month incidence of medically
      certified sickness absence was calculated for each year by dividing incident
      episodes by the number of employees. Sick days due to common mental disorders
      were computed as percentage of the total number of medically certified sick days.
      RESULTS: The 12-month incidence of sickness absence due to common mental
      disorders was 2.2% in 2001, increased to 2.7% in 2004 and decreased thereafter to
      2.0% in 2007. The percentage of sick days due to common mental disorders was
      highest in the education sector (39%) followed by financial services (31%) and
      health care (30%). CONCLUSIONS: In the Netherlands, the incidence of sickness
      absence with common mental disorders was highest in 2004 and has decreased since
      then probably because of changes in sick leave compensation, economic market
      position and company policies.

PMID- 19581375
TI  - Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL
      37 is not proinflammatory to phagocytosing macrophages.
AB  - Cathelicidins are CHDP with essential roles in innate host defense but also more
      recently associated with the pathogenesis of certain chronic diseases. These
      peptides have microbicidal potential and the capacity to modulate innate immunity
      and inflammatory processes. PMN are key innate immune effector cells with pivotal
      roles in defense against infection. The appropriate regulation of PMN function,
      death, and clearance is critical to innate immunity, and dysregulation is
      implicated in disease pathogenesis. The efferocytosis of apoptotic PMN, in
      contrast to necrotic cells, is proposed to promote the resolution of
      inflammation. We demonstrate that the human cathelicidin LL-37 induced rapid
      secondary necrosis of apoptotic human PMN and identify an essential minimal
      region of LL-37 required for this activity. Using these LL-37-induced secondary
      necrotic PMN, we characterize the consequence for macrophage inflammatory
      responses. LL-37-induced secondary necrosis did not inhibit PMN ingestion by
      monocyte-derived macrophages and in contrast to expectation, was not
      proinflammatory. Furthermore, the anti-inflammatory effects of apoptotic PMN on
      activated macrophages were retained and even potentiated after LL-37-induced
      secondary necrosis. However, this process of secondary necrosis did induce the
      release of potentially harmful PMN granule contents. Thus, we suggest that LL-37
      can be a potent inducer of PMN secondary necrosis during inflammation without
      promoting macrophage inflammation but may mediate host damage through PMN granule
      content release under chronic or dysregulated conditions.

PMID- 19581378
TI  - The kinaesthetic senses.
AB  - This review of kinaesthesia, the senses of limb position and limb movement, has
      been prompted by recent new observations on the role of motor commands in
      position sense. They make it necessary to reassess the present-day views of the
      underlying neural mechanisms. Peripheral receptors which contribute to
      kinaesthesia are muscle spindles and skin stretch receptors. Joint receptors do
      not appear to play a major role at most joints. The evidence supports the
      existence of two separate senses, the sense of limb position and the sense of
      limb movement. Receptors such as muscle spindle primary endings are able to
      contribute to both senses. While limb position and movement can be signalled by
      both skin and muscle receptors, new evidence has shown that if limb muscles are
      contracting, an additional cue is provided by centrally generated motor command
      signals. Observations using neuroimaging techniques indicate the involvement of
      both the cerebellum and parietal cortex in a multi-sensory comparison, involving
      operation of a forward model between the feedback during a movement and its
      expected profile, based on past experience. Involvement of motor command signals
      in kinaesthesia has implications for interpretations of certain clinical
      conditions.

PMID- 19581379
TI  - Excitability of paraventricular nucleus neurones that project to the rostral
      ventrolateral medulla is regulated by small-conductance Ca2+-activated K+
      channels.
AB  - Whole cell patch-clamp recordings were performed in brain slices to investigate
      mechanisms regulating the excitability of paraventricular nucleus (PVN) neurones
      that project directly to the rostral ventrolateral medulla (RVLM) (PVN-RVLM
      neurones) of rats. In voltage-clamp recordings, step depolarization elicited a
      calcium-dependent outward tail current that reversed near E(K). The current was
      nearly abolished by apamin and by UCL1684, suggesting mediation by small
      conductance Ca(2+)-activated K(+) (SK) channels. In current-clamp recordings,
      depolarizing step current injections evoked action potentials that underwent
      spike-frequency adaptation (SFA). SK channel blockade with apamin or UCL1684
      increased the spike frequency without changing the rate of SFA. Upon termination
      of step current injection, a prominent medium after-hyperpolarization potential
      (mAHP) was observed. SK channel blockade abolished the mAHP and revealed an after
      depolarization potential (ADP). In response to ramp current injections, the rate
      of sub-threshold depolarization was increased during SK channel blockade,
      indicating that depolarizing input resistance was increased. Miniature EPSC
      frequency, amplitude, and decay kinetics were unaltered by bath application of
      apamin, suggesting that SK channel blockade likely increased excitability by a
      postsynaptic action. We conclude that although SK channels play little role in
      generating SFA in PVN-RVLM neurones, their activation nevertheless does dampen
      excitability. The mechanism appears to involve activation of a mAHP that opposes
      a prominent ADP that would otherwise facilitate firing.

PMID- 19581380
TI  - EPAC signalling pathways are involved in low PO2 chemoreception in carotid body
      chemoreceptor cells.
AB  - Chemoreceptor cells of the carotid bodies (CB) are activated by hypoxia and
      acidosis, responding with an increase in their rate of neurotransmitter release,
      which in turn increases the electrical activity in the carotid sinus nerve and
      evokes a homeostatic hyperventilation. Studies in isolated chemoreceptor cells
      have shown that moderate hypoxias ( 46 mmHg) produces smaller depolarisations and
      comparable Ca(2+) transients but a much higher catecholamine (CA) release
      response in intact CBs than intense acidic/hypercapnic stimuli (20% CO(2), pH
      6.6). Similarly, intense hypoxia ( 20 mmHg) produces smaller depolarizations and
      Ca(2+) transients in isolated chemoreceptor cells but a higher CA release
      response in intact CBs than a pure depolarizing stimulus (30-35 mm external
      K(+)). Studying the mechanisms responsible for these differences we have found
      the following. (1) Acidic hypercapnia inhibited I(Ca) (60%; whole cell) and CA
      release (45%; intact CB) elicited by ionomycin and high K(+). (2) Adenylate
      cyclase inhibition (SQ-22536; 80 microm) inhibited the hypoxic release response
      (>50%) and did not affect acidic/hypercapnic release, evidencing that the high
      gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The
      last effect was independent of PKA activation, as three kinase inhibitors (H-89,
      KT 5720 and Rp-cAMP; 10 x IC(50)) did not alter the hypoxic release response. (4)
      The Epac (exchange protein activated by cAMP) activator (8-pCPT-2-O-Me-cAMP, 100
      microm) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor
      brefeldin A (100 microm) inhibited (54%) hypoxic induced release. Our findings
      show for the first time that an Epac-mediated pathway mediates O(2)
      sensing/transduction in chemoreceptor cells.

PMID- 19581381
TI  - Sodium-calcium exchangers contribute to the regulation of cytosolic calcium
      levels in mouse taste cells.
AB  - Taste cells use multiple signalling mechanisms to generate unique calcium
      responses to distinct taste stimuli. Some taste stimuli activate G-protein
      coupled receptors (GPCRs) that cause calcium release from intracellular stores
      while other stimuli depolarize taste cells to cause calcium influx through
      voltage-gated calcium channels (VGCCs). We recently demonstrated that a
      constitutive calcium influx exists in taste cells that is regulated by
      mitochondrial calcium transport and that the magnitude of this calcium influx
      correlates with the signalling mechanisms used by the taste cells. In this study,
      we used calcium imaging to determine that sodium-calcium exchangers (NCXs) also
      routinely contribute to the regulation of basal cytosolic calcium and that their
      relative role correlates with the signalling mechanisms used by the taste cells.
      RT-PCR analysis revealed that multiple NCXs and sodium-calcium-potassium
      exchangers (NCKXs) are expressed in taste cells. Thus, a dynamic relationship
      exists between calcium leak channels and calcium regulatory mechanisms in taste
      cells that functions to keep cytosolic calcium levels in the appropriate range
      for cell function.

PMID- 19581382
TI  - Presentation and severity of rheumatoid arthritis at diagnosis in Senegal.
AB  - OBJECTIVE: Early effective treatment slows structural damage in RA but requires
      an early diagnosis. Our objective was to determine symptoms duration and
      presentation patterns of RA at diagnosis in Senegal. METHODS: We conducted a
      cross-sectional study over a 2-year period (from March 2006 to February 2008) at
      the rheumatology clinic of the Le Dantec teaching hospital in Dakar, Senegal.
      Consecutive new patients who met ACR criteria for RA were included. RESULTS: We
      included 100 patients, 88 females and 12 males, with a mean age of 40.3 +/- 15.5
      years and a mean symptoms duration of 54 months. One-fourth of the patients had a
      positive family history. Pain was the main reason for the rheumatology clinic
      visit. Mean pain score was 64.3 mm on a 100-mm visual analogue scale. Nocturnal
      arousals were reported by 69% of the patients and morning stiffness for >1 h by
      74%. The tender and swollen joint counts were 10 or higher in 87% and 36% of the
      patients, respectively, and the mean disease activity score on 28 joints (DAS28)
      was 6.49 +/- 1.34. Sicca syndrome (n = 13) and rheumatoid nodules (n = 3) were
      the main extra-articular manifestations. Laboratory evidence of inflammation was
      found in 87% and RF in 78% of the patients. Antibodies to cyclic citrullinated
      peptides (anti-CCPs) were detected in 26 of the 29 patients. Radiographical
      lesions were visible in 56% of the patients; mean modified Sharp score was 21.76
      +/- 47.74. CONCLUSION: The diagnosis of RA is delayed in Senegal, and the disease
      is highly active at diagnosis, although 44 patients have no erosions, and extra
      articular manifestations are rare.

PMID- 19581383
TI  - Sarcoidosis or scleroderma? An unusual case of sarcoidosis in a 3-year-old
      Caucasian girl.

PMID- 19581384
TI  - Illness awareness in hospice: application of a semi-structured interview.
AB  - This study describes the results of a semi-structured interview to assess the
      illness awareness of cancer patients in Hospice. The results of this study are
      based on the interviews made in Rimini and Savignano sul Rubicone Hospices (n =
      51). Psychologists evaluated illness awareness of the participants interviewed
      independently from the code system that is provided for the interview. According
      to the psychologists, 18 patients (35%) were aware, 11 patients (22%) were
      unaware, and 22 patients (43%) were aware with defense mechanisms. According to
      the code system of the interview, the results were the following: 18 patients
      (35%) were aware, 2 patients (4%) were unaware, and 29 patients (57%) were aware
      with defense mechanisms. Two participants had to be reassessed because of
      inconsistency in some factors. In conclusion, the data analysis underlined that
      the congruence of the 2 assessment methods was found in 33 of the 51 patients
      examined (65%) and that the degree of concordance was rather low (kappa = .46;
      95% CI = 0.24-0.68).

PMID- 19581385
TI  - Toward a new definition of health disparity: a concept analysis.
AB  - In response to federal requests for investigation into measures to eradicate
      health disparities, a concept analysis of the term health disparity was
      conducted. Health-related and multidisciplinary literature was reviewed. Multiple
      terms were explored alone and in combination with no limitations on search date
      parameters. Findings indicated several definitions of the concept,with the term
      health care disparity being used interchangeably with the term health disparity.
      New theoretical and operational definitions, antecedents, characteristics, and
      consequences of the concept are proffered. Model, borderline, and contrary cases
      are developed to illustrate the concept. Nursing implications and recommendations
      for future research are discussed.

PMID- 19581386
TI  - Presystemic elimination of trichloroethylene in rats following environmentally
      relevant oral exposures.
AB  - 1,1,2-Trichloroethylene (TCE), a volatile organic contaminant (VOC) of drinking
      water in the Unites States, is frequently present in trace amounts. TCE is
      currently classified by the International Agency for Research on Cancer and the
      U.S. Environmental Protection Agency as a probable human carcinogen, because it
      produces tumors in some organs of certain strains of mice or rats in chronic,
      high-dose bioassays. Previous studies (Toxicol Appl Pharmacol 60:509-526, 1981;
      Regul Toxicol Pharmacol 8:447-466, 1988) used physiological modeling principles
      to reason that the liver should remove virtually all of a well metabolized VOC,
      such as TCE, as long as concentrations in the portal blood were not high enough
      to saturate metabolism. To test this hypothesis, groups of unanesthetized male
      Sprague-Dawley rats received intravenous injections of 0.1, 1.0, or 2.5 mg TCE/kg
      as an aqueous emulsion. Other rats were gavaged with 0.0001, 0.001, 0.01, 0.1, 1,
      2.5, 5, or 10 mg TCE/kg b.wt. Serial microblood samples were taken via an
      indwelling carotid artery cannula, to generate blood TCE versus time profiles.
      Headspace solid-phase microextraction gas chromatography with negative chemical
      ionization mass spectrometry (limit of quantitation = 25 pg/ml) was used to
      quantify TCE. TCE was undetectable in rats given 0.0001 mg/kg, but it exhibited
      linear kinetics from 0.1 to 5.0 mg/kg. Bioavailability was consistent over this
      dosage range, ranging from 12.5 to 16.4%. The presence of these limited amounts
      of TCE in the arterial blood disprove the aforementioned hypothesis, yet
      demonstrate that first-pass hepatic and pulmonary elimination in the rat afford
      its extrahepatic organs protection from potential adverse effects by the majority
      of the low levels of TCE absorbed from drinking water.

PMID- 19581387
TI  - Allele and genotype frequencies of cytochrome P450 2B6 gene in a Mongolian
      population.
AB  - CYP2B6 plays an important role in metabolizing various drugs in common clinical
      use. Increasing interest in CYP2B6 genetic polymorphism was stimulated by
      revelations of a specific CYP2B6 genotype significantly affecting the metabolism
      of efavirenz, an anti-HIV type-1 agent. The present study determined the CYP2B6
      haplotype in 100 healthy unrelated Mongolian volunteers by analyzing the
      genotypes of nine single nucleotide polymorphism (SNP) positions (-82T>C, 64C>T,
      499C>T, 516G>T, 777C>A, 785A>G, 983T>C, 1375A>G, and 1459C>T) in the CYP2B6 gene.
      The CYP2B6 *1 allele was the most frequent in the Mongolian population tested at
      64.5%, higher than the equivalent frequency in African-Americans and Ghanaians.
      The second most frequent allele was CYP2B6 *6 (21.0%), although this allele was
      less frequent than that in Ghanaians. Only one CYP2B6 *5 allele was identified in
      our Mongolian subjects (0.5%), although it is the third most frequent allele in
      white and African-American populations. These CYP2B6 genotypes revealed seven
      slow efavirenz metabolizers in 100 Mongolians, which is significantly fewer than
      the same group among Ghanaians. Overall, the Mongolian CYP2B6 allele distribution
      was comparable with that in Japanese, Koreans, and Han Chinese. This is the first
      report of CYP2B6 genotype frequency in a Mongolian population, and it could
      provide clinically useful information on drug metabolism in this population
      group.

PMID- 19581388
TI  - MicroRNAs regulate CYP3A4 expression via direct and indirect targeting.
AB  - CYP3A4 metabolizes many drugs on the market. Although transcriptional regulation
      of CYP3A4 is known to be tightly controlled by some nuclear receptors (NR)
      including vitamin D receptor (VDR/NR1I1), posttranscriptional regulation of
      CYP3A4 remains elusive. In this study, we show that noncoding microRNAs (miRNAs)
      may control posttranscriptional and transcriptional regulation of CYP3A4 by
      directly targeting the 3'-untranslated region (3'UTR) of CYP3A4 and indirectly
      targeting the 3'UTR of VDR, respectively. Luciferase reporter assays showed that
      CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic
      kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b)
      or mouse microRNA-298 (mmu-miR-298), whereas the activity was unchanged in cells
      transfected with plasmid that expressed microRNA-122a or microRNA-328. Disruption
      of the corresponding miRNA response element (MRE) within CYP3A4 3'UTR led to a 2-
      to 3-fold increase in luciferase activity. Immunoblot analyses indicated that
      CYP3A4 protein was down-regulated over 30% by miR-27b and mmu-miR-298 in LS-180
      and PANC1 cells. The decrease in CYP3A4 protein expression was associated with
      significantly decreased CYP3A4 mRNA levels, as determined by quantitative real
      time PCR (qPCR) analyses. Likewise, interactions of miR-27b or mmu-miR-298 with
      VDR 3'UTR were supported by luciferase reporter assays. The mmu-miR-298 MRE site
      is well conserved within the 3'UTR of mouse, rat, and human VDR. Down-regulation
      of VDR by the two miRNAs was supported by immunoblot and qPCR analyses.
      Furthermore, overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a
      lower sensitivity to cyclophosphamide. Together, these findings suggest that
      CYP3A4 gene expression may be regulated by miRNAs at both the transcriptional and
      posttranscriptional level.

PMID- 19581389
TI  - Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2
      Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726)
      pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis.
AB  - Leflunomide is a disease-modifying antirheumatic drug used for the treatment of
      rheumatoid arthritis (RA). Cytochromes P450, mainly CYP1A2 and CYP2C19, may be
      involved in the transformation of leflunomide to leflunomide metabolite (A77
      1726, 2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide). The aim of
      this study was to investigate whether genetic polymorphisms in CYP1A2 and CYP2C19
      influence leflunomide pharmacokinetics, treatment response, and the occurrence of
      adverse drug reactions (ADRs). The study included 67 patients with RA and 4
      patients with polyarthritis resembling RA and psoriasis treated with leflunomide.
      A77 1726 steady-state plasma concentrations were determined by validated high
      performance liquid chromatography with UV detection. A population pharmacokinetic
      model was developed to estimate the oral clearance (CL/F) and volume of
      distribution (V/F). A genotyping approach was used to determine C-163A, C-729T,
      and T-739G in the CYP1A2 gene as well as single nucleotide polymorphisms that
      characterize CYP2C19*2, *3, *4, and *17 alleles. A large interindividual
      variability in trough A77 1726 steady-state plasma concentrations was observed
      (from 1.9 to 156.9 mg/l). A77 1726 CL/F was 71% higher in carriers of the
      CYP2C19*2 allele compared with noncarriers. The A77 1726 average steady-state
      plasma concentration was associated with the treatment response. Patients with a
      greater decrease in C-reactive protein (CRP) had higher average steady-state
      plasma A77 1726 concentrations: 49.7 +/- 39.0 mg/l in patients with DeltaCRP of
      more than 8.5 mg/l compared with 24.8 +/- 13.7 mg/l in patients with DeltaCRP of
      <or=8.5 mg/l (p = 0.015). No association of A77 1726 steady-state plasma
      concentrations with the occurrence of ADRs was observed. Our results suggest that
      genetic variability in leflunomide-metabolizing enzymes influences leflunomide
      metabolite concentrations that are associated with the treatment response but not
      with leflunomide-induced toxicity.

PMID- 19581390
TI  - Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in
      mice.
AB  - The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin
      D(3) and mediates regulation of calcium homeostasis. Bile acids, such as
      lithocholic acid, have been identified as additional endogenous VDR ligands. The
      in vivo role of VDR in bile acid metabolism has not been elucidated. We
      investigated potential effects of in vivo VDR activation on bile acid metabolism
      by feeding mice bile acid-supplemented chow and then treating them with 1alpha
      hydroxyvitamin D(3) [1alpha(OH)D(3)]. We administered 1alpha(OH)D(3) via gavage
      to mice fed chow supplemented with 0.4% cholic acid (CA), chenodeoxycholic acid
      (CDCA), deoxycholic acid (DCA), or lithocholic acid (LCA) and examined liver and
      plasma bile acid composition with gas chromatography-mass spectrometry analysis.
      1alpha(OH)D(3) treatment reduced hepatic bile acids in mice fed CDCA- and DCA
      supplemented chow but was less effective in mice fed chow supplemented with LCA
      or CA. 1alpha(OH)D(3) administration also decreased plasma bile acids in mice fed
      bile acids, such as DCA. The effect of 1alpha(OH)D(3) administration in
      decreasing liver bile acid composition was observed in mice under fasting
      conditions and was associated with increased urinary excretion and increased
      expression of bile acid transporters, such as renal multidrug resistance
      associated protein 4. These findings indicate that pharmacological activation of
      VDR enhances metabolism of bile acids, especially urinary excretion. The results
      confirm that VDR acts a regulator of bile acid metabolism in vivo.

PMID- 19581391
TI  - Toward the rational design of a malaria vaccine construct using the MSP3 family
      as an example: contribution of immunogenicity studies in models.
AB  - Plasmodium falciparum merozoite surface protein 3 (MSP3), the target of
      antibodies that mediate parasite killing in cooperation with blood monocytes and
      are associated with protection in exposed populations, is a vaccine candidate
      under development. It belongs to a family of six structurally related genes. To
      optimize immunogenicity, we attempted to improve its design based on knowledge of
      antigenicity of various regions from the conserved C terminus of the six proteins
      and an analysis of the immunogenicity of "tailored" constructs. The
      immunogenicity studies were conducted in BALB/c and C57BL/6J mice, using MSP3
      (referred to here as MSP3-1) as a model. Four constructs were designed in order
      to assess the effect of sequences flanking the 69-amino-acid region of MSP3-1
      previously shown to be the target of biologically active antibodies. The results
      indicate major beneficial effects of removing (i) the subregion downstream from
      the 69-amino-acid sequence, since antibody titers increased by 2 orders of
      magnitude, and (ii) the upstream subregion which, although it defines a T-helper
      cell epitope, is not the target of antibodies. The construct, excluding both
      flanking sequences, was able to induce Th1-like responses, with a dominance of
      cytophilic antibodies. This led to design a multigenic construct based on these
      results, combining the six members of the MSP3 family. This new construction was
      immunogenic in mice, induced antibodies that recognized the parasite native
      proteins, and inhibited parasite growth in the functional antibody-dependent
      cellular inhibition assay, thus satisfying the preclinical criteria for a
      valuable vaccine candidate.

PMID- 19581392
TI  - Plasminogen acquisition and activation at the surface of leptospira species lead
      to fibronectin degradation.
AB  - Pathogenic Leptospira species are the etiological agents of leptospirosis, a
      widespread disease of human and veterinary concern. In this study, we report that
      Leptospira species are capable of binding plasminogen (PLG) in vitro. The binding
      to the leptospiral surface was demonstrated by indirect immunofluorescence
      confocal microscopy with living bacteria. The PLG binding to the bacteria seems
      to occur via lysine residues because the ligation is inhibited by addition of the
      lysine analog 6-aminocaproic acid. Exogenously provided urokinase-type PLG
      activator (uPA) converts surface-bound PLG into enzymatically active plasmin, as
      evaluated by the reaction with the chromogenic plasmin substrate d-Val-Leu-Lys 4
      nitroanilide dihydrochloridein. The PLG activation system on the surface of
      Leptospira is PLG dose dependent and does not cause injury to the organism, as
      cellular growth in culture was not impaired. The generation of active plasmin
      within Leptospira was observed with several nonvirulent high-passage strains and
      with the nonpathogenic saprophytic organism Leptospira biflexa. Statistically
      significant higher activation of plasmin was detected with a low-passage
      infectious strain of Leptospira. Plasmin-coated virulent Leptospira interrogans
      bacteria were capable of degrading purified extracellular matrix fibronectin. The
      breakdown of fibronectin was not observed with untreated bacteria. Our data
      provide for the first time in vitro evidence for the generation of active plasmin
      on the surface of Leptospira, a step that may contribute to leptospiral
      invasiveness.

PMID- 19581393
TI  - Further characterization of the epa gene cluster and Epa polysaccharides of
      Enterococcus faecalis.
AB  - We previously identified a gene cluster, epa (for enterocococcal polysaccharide
      antigen), involved in polysaccharide biosynthesis of Enterococcus faecalis and
      showed that disruption of epaB and epaE resulted in attenuation in translocation,
      biofilm formation, resistance to polymorphonuclear leukocyte (PMN) killing, and
      virulence in a mouse peritonitis model. Using five additional mutant disruptions
      in the 26-kb region between orfde2 and OG1RF_0163, we defined the epa locus as
      the area from epaA to epaR. Disruption of epaA, epaM, and epaN, like prior
      disruption of epaB and epaE, resulted in alteration in Epa polysaccharide
      content, more round cells versus oval cells with OG1RF, decreased biofilm
      formation, attenuation in a mouse peritonitis model, and resistance to lysis by
      the phage NPV-1 (known to lyse OG1RF), while mutants disrupted in orfde2 and
      OG1RF_163 (the epa locus flanking genes) behaved like OG1RF in those assays.
      Analysis of the purified Epa polysaccharide from OG1RF revealed the presence of
      rhamnose, glucose, galactose, GalNAc, and GlcNAc in this polysaccharide, while
      carbohydrate preparation from the epaB mutant did not contain rhamnose,
      suggesting that one or more of the glycosyl transferases encoded by the epaBCD
      operon are necessary to transfer rhamnose to the polysaccharide. In conclusion,
      the epa genes, uniformly present in E. faecalis strains and involved in
      biosynthesis of polysaccharide in OG1RF, are also important for OG1RF shape
      determination, biofilm formation, and NPV-1 replication/lysis, as well as for E.
      faecalis virulence in a mouse peritonitis model.

PMID- 19581394
TI  - The RNA binding protein CsrA is a pleiotropic regulator of the locus of
      enterocyte effacement pathogenicity island of enteropathogenic Escherichia coli.
AB  - The attaching and effacing (A/E) pathogen enteropathogenic Escherichia coli
      (EPEC) forms characteristic actin-filled membranous protrusions upon infection of
      host cells termed pedestals. Here we examine the role of the RNA binding protein
      CsrA in the expression of virulence genes and proteins that are necessary for
      pedestal formation. The csrA mutant was defective in forming actin pedestals on
      epithelial cells and in disrupting transepithelial resistance across polarized
      epithelial cells. Consistent with reduced pedestal formation, secretion of the
      translocators EspA, EspB, and EspD and the effector Tir was substantially reduced
      in the csrA mutant. Purified CsrA specifically bound to the sepL espADB mRNA
      leader, and the corresponding transcript levels were reduced in the csrA mutant.
      In contrast, Tir synthesis was unaffected in the csrA mutant. Reduced secretion
      of Tir appeared to be in part due to decreased synthesis of EscD, an inner
      membrane architectural protein of the type III secretion system (TTSS) and EscF,
      a protein that forms the protruding needle complex of the TTSS. These effects
      were not mediated through the locus of enterocyte effacement (LEE)
      transcriptional regulator GrlA or Ler. In contrast to the csrA mutant, multicopy
      expression of csrA repressed transcription from LEE1, grlRA, LEE2, LEE5, escD,
      and LEE4, an effect mediated by GrlA and Ler. Consistent with its role in other
      organisms, CsrA also regulated flagellar motility and glycogen levels. Our
      findings suggest that CsrA governs virulence factor expression in an A/E pathogen
      by regulating mRNAs encoding translocators, effectors, or transcription factors.

PMID- 19581395
TI  - A transmembrane domain-containing surface protein from Toxoplasma gondii augments
      replication in activated immune cells and establishment of a chronic infection.
AB  - Toxoplasma gondii mutants identified as defective in the establishment of chronic
      infection were screened to isolate those specifically impaired in their ability
      to replicate within activated macrophages. One of the identified mutants contains
      an insertion in the hypothetical gene TGME49_111670. Genetic complementation
      restores the ability of the mutant to replicate in immune cells and produce cysts
      in the brains of mice. While the mutant is more sensitive to nitric oxide than is
      its parental strain, it is not defective in its ability to suppress nitric oxide.
      The disrupted protein has no significant homology to proteins with known
      functions, but is predicted to have one transmembrane domain. Immunofluorescence
      shows the protein on the parasite surface, even in activated macrophages,
      colocalizing with a tachyzoite surface antigen, SAG1, and oriented with its C
      terminal end external. Western analysis reveals that the protein is downregulated
      in bradyzoites. Despite the tachyzoite specificity of this protein, mice infected
      with the mutant succumb to acute infection similarly to those infected with the
      parent strain. Serum samples from mice with chronic T. gondii infection react to
      a polypeptide from TGME49_11670, indicating that the protein is seen by the
      immune system during infection. This study is the first to characterize a T.
      gondii surface protein that contains a transmembrane domain and show that the
      protein contributes to parasite replication in activated immune cells and the
      establishment of chronic infection.

PMID- 19581396
TI  - Gr1+ cells control growth of YopM-negative yersinia pestis during systemic
      plague.
AB  - YopM, a protein toxin of Yersinia pestis, is necessary for virulence in a mouse
      model of systemic plague. We previously reported YopM-dependent natural killer
      (NK) cell depletion from blood and spleen samples of infected mice. However, in
      this study we found that infection with Y. pestis KIM5 (YopM(+)) caused depletion
      of NK cells in the spleen, but not in the liver, and antibody-mediated ablation
      of NK cells had no effect on bacterial growth. There was no YopM-associated
      effect on the percentage of dendritic cells (DCs) or polymorphonuclear leukocytes
      (PMNs) in the early stage of infection; however, there was a YopM-associated
      effect on PMN integrity and on the influx of monocytes into the spleen. Ablation
      of Gr1(+) cells caused loss of the growth defect of YopM(-) Y. pestis in both the
      liver and spleen. In contrast, ablation of macrophages/DCs inhibited growth of
      both parent and mutant bacteria, accompanied by significantly fewer lesion sites
      in the liver. These results point toward PMNs and inflammatory monocytes as major
      cell types that control growth of YopM(-) Y. pestis. Infection with fully
      virulent Y. pestis CO92 and a YopM(-) derivative by intradermal and intranasal
      routes showed that the absence of YopM significantly increased the 50% lethal
      dose only in the intradermal model, suggesting a role for YopM in bubonic plague,
      in which acute inflammation occurs soon after infection.

PMID- 19581397
TI  - Complement C3 plays an essential role in the control of opportunistic fungal
      infections.
AB  - The innate recognition of fungal pathogens is a crucial first step in the
      induction of protective antifungal immunity. Complement is thought to be one key
      component in this process, facilitating fungal recognition and inducing early
      inflammation. However, the roles of the individual complement components have not
      been examined extensively. Here we have used mice lacking C3 to examine its role
      in immunity to opportunistic fungal pathogens and show that this complement
      component is essential for resistance to infections with Candida albicans and
      Candida glabrata. We demonstrate that the absence of C3 impairs fungal clearance
      but does not affect inflammatory responses. We also show that the presence of C3
      contributes to mortality in mice challenged with very high doses of Saccharomyces
      cerevisiae, although these effects were found to be mouse strain dependent.

PMID- 19581398
TI  - Relevant role of fibronectin-binding proteins in Staphylococcus aureus biofilm
      associated foreign-body infections.
AB  - Staphylococcus aureus can establish chronic infections on implanted medical
      devices due to its capacity to form biofilms. Analysis of the factors that
      assemble cells into a biofilm has revealed the occurrence of strains that produce
      either a polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG)
      exopolysaccharide- or a protein-dependent biofilm. Examination of the influence
      of matrix nature on the biofilm capacities of embedded bacteria has remained
      elusive, because a natural strain that readily converts between a polysaccharide-
      and a protein-based biofilm has not been studied. Here, we have investigated the
      clinical methicillin (meticillin)-resistant Staphylococcus aureus strain 132,
      which is able to alternate between a proteinaceous and an exopolysaccharidic
      biofilm matrix, depending on environmental conditions. Systematic disruption of
      each member of the LPXTG surface protein family identified fibronectin-binding
      proteins (FnBPs) as components of a proteinaceous biofilm formed in Trypticase
      soy broth-glucose, whereas a PIA/PNAG-dependent biofilm was produced under
      osmotic stress conditions. The induction of FnBP levels due to a spontaneous agr
      deficiency present in strain 132 and the activation of a LexA-dependent SOS
      response or FnBP overexpression from a multicopy plasmid enhanced biofilm
      development, suggesting a direct relationship between the FnBP levels and the
      strength of the multicellular phenotype. Scanning electron microscopy revealed
      that cells growing in the FnBP-mediated biofilm formed highly dense aggregates
      without any detectable extracellular matrix, whereas cells in a PIA/PNAG
      dependent biofilm were embedded in an abundant extracellular material. Finally,
      studies of the contribution of each type of biofilm matrix to subcutaneous
      catheter colonization revealed that an FnBP mutant displayed a significantly
      lower capacity to develop biofilm on implanted catheters than the isogenic
      PIA/PNAG-deficient mutant.

PMID- 19581400
TI  - Adhesion of Candida albicans to endothelial cells under physiological conditions
      of flow.
AB  - Candida albicans is a commensal organism that under certain circumstances can
      become pathogenic. During systemic infection C. albicans is disseminated via the
      circulation to distant organs, where it causes multiple organ failure. Despite
      the severity of systemic C. albicans infection, little is known about the
      mechanisms involved in the adhesion of this organism to the endothelium lining
      blood vessels. Previous studies have used static assays to examine adhesion.
      However, these do not realistically model blood vessels, where circulating C.
      albicans cells must adhere to the endothelium under conditions of flow and shear
      stress. Furthermore, there is conflicting evidence concerning the role played by
      yeast, pseudohyphal, and hyphal forms of C. albicans in adhesion to endothelium.
      To test the hypothesis that there may be differences in the abilities of these
      three morphogenic forms of C. albicans to adhere to endothelium under conditions
      of flow, we developed an in vitro flow adhesion assay. We found that all three
      forms of C. albicans rapidly bound to confluent endothelial cells under
      conditions of flow. Maximum adhesion was found at low shear stress levels similar
      to that found in postcapillary venules. Moreover, yeast forms bound in
      significantly greater numbers than did pseudohyphal and hyphal forms,
      respectively, contrasting with previous findings from static assays. These
      findings are consistent with recent in vivo data suggesting that yeast forms may
      be capable of adhering to the endothelium and migrating into the tissues before
      undergoing morphogenic change to cause tissue damage.

PMID- 19581399
TI  - Human alpha-defensins inhibit hemolysis mediated by cholesterol-dependent
      cytolysins.
AB  - Many pathogenic gram-positive bacteria release exotoxins that belong to the
      family of cholesterol-dependent cytolysins. Here, we report that human alpha
      defensins HNP-1 to HNP-3 acted in a concentration-dependent manner to protect
      human red blood cells from the lytic effects of three of these exotoxins:
      anthrolysin O (ALO), listeriolysin O, and pneumolysin. HD-5 was very effective
      against listeriolysin O but less effective against the other toxins. Human alpha
      defensins HNP-4 and HD-6 and human beta-defensin-1, -2, and -3 lacked protective
      ability. HNP-1 required intact disulfide bonds to prevent toxin-mediated
      hemolysis. A fully linearized analog, in which all six cysteines were replaced by
      aminobutyric acid (Abu) residues, showed greatly reduced binding and protection.
      A partially unfolded HNP-1 analog, in which only cysteines 9 and 29 were replaced
      by Abu residues, showed intact ALO binding but was 10-fold less potent in
      preventing hemolysis. Surface plasmon resonance assays revealed that HNP-1 to HNP
      3 bound all three toxins at multiple sites and also that solution-phase HNP
      molecules could bind immobilized HNP molecules. Defensin concentrations that
      inhibited hemolysis by ALO and listeriolysin did not prevent these toxins from
      binding either to red blood cells or to cholesterol. Others have shown that HNP-1
      to HNP-3 inhibit lethal toxin of Bacillus anthracis, toxin B of Clostridium
      difficile, diphtheria toxin, and exotoxin A of Pseudomonas aeruginosa; however,
      this is the first time these defensins have been shown to inhibit pore-forming
      toxins. An "ABCDE mechanism" that can account for the ability of HNP-1 to HNP-3
      to inhibit so many different exotoxins is proposed.

PMID- 19581403
TI  - Total mortality after changes in leisure time physical activity in 50 year old
      men: 35 year follow-up of population based cohort.
AB  - OBJECTIVE: To examine how change in level of physical activity after middle age
      influences mortality and to compare it with the effect of smoking cessation.
      DESIGN: Population based cohort study with follow-up over 35 years. SETTING:
      Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who
      were reexamined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total
      (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and
      18.4 per 1000 person years in the groups with low, medium, and high physical
      activity, respectively. The relative rate reduction attributable to high physical
      activity was 32% for low and 22% for medium physical activity. Men who increased
      their physical activity level between the ages of 50 and 60 continued to have a
      higher mortality rate during the first five years of follow-up (adjusted hazard
      ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high
      physical activity). After 10 years of follow-up their increased physical activity
      was associated with reduced mortality to the level of men with unchanged high
      physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated
      with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low
      physical activity) was similar to that associated with smoking cessation (0.64,
      0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical
      activity in middle age is eventually followed by a reduction in mortality to the
      same level as seen among men with constantly high physical activity. This
      reduction is comparable with that associated with smoking cessation.

PMID- 19581405
TI  - Myopia and later physical activity in adolescence: a prospective study.
AB  - OBJECTIVES: To investigate associations between objectively measured physical
      activity (PA) and myopia in children. METHODS: Children from the Avon
      Longitudinal Study of Parents and Children (ALSPAC) were asked to wear a uniaxial
      accelerometer for 7 days. Measures of counts per minute (cpm), minutes spent in
      moderate to vigorous activity (MVPA) and minutes of sedentary behaviour (msed)
      were derived from the accelerometer worn at age 12. Children were also examined,
      at age 10, using an autorefractor to estimate myopia. Social and parental factors
      were collected from pregnancy and physical measures of the child were recorded at
      age 12. RESULTS: 4880 children had valid PA and autorefraction data. In minimally
      adjusted models (age and gender) myopic children were less active than the other
      children: beta = -49.9 cpm (95% CI -73.5 to -26.4, p = <0.001). The myopic group
      spent less time in MVPA than the other children: beta = -3.2 minutes MVPA (95% CI
      -5.2 to -1.1, p = 0.003) and more time sedentary: beta = 15.8 minutes (95% CI 5.8
      to 25.8, p = 0.002). The effect sizes were attenuated by adjustment for social
      and behavioural confounders although myopia status in the better (less myopic on
      autorefraction) eye remained strongly associated with cpm and MVPA but less so
      for sedentary behaviour: beta = -36.8 cpm (95% CI -67.8 to -5.8, p = 0.02), beta
      = -2.7 MVPA (95% CI -5.3 to -0.1, p = 0.04), beta = 10.1 msed (95% CI -2.9 to
      23.1, p = 0.13). CONCLUSION: Myopic children may be more at risk of having lower
      levels of PA than their non-myopic peers, although the difference was modest.

PMID- 19581401
TI  - MicroRNAs and their role in progressive kidney diseases.
AB  - MicroRNAs (miRs) are a family of short non-coding RNAs. These endogenously
      produced factors have been shown to play important roles in gene regulation. The
      discovery of miRs has greatly expanded our knowledge of gene regulation at the
      posttranscriptional level. miRs inhibit target gene expression by blocking
      protein translation or by inducing mRNA degradation and therefore have the
      potential to modulate physiologic and pathologic processes. The imperative need
      to determine their cellular targets and disease relevance has sparked an
      unprecedented explosion of research in the miR field. Recent findings have
      revealed critical functions for specific miRs in cellular events such as
      proliferation, differentiation, development, and immune responses and in the
      regulation of genes relevant to human diseases. Of particular interest to renal
      researchers are recent reports that key miRs are highly expressed in the kidney
      and can act as effectors of TGF-beta actions and high glucose in diabetic kidney
      disease. Moreover, podocyte-specific deletion of Dicer, a key enzyme involved in
      miR biogenesis, led to proteinuria and severe renal dysfunction in mice. Hence,
      studies aimed at determining the in vitro and in vivo functions of miRs in the
      kidney could determine their value as therapeutic targets for progressive renal
      glomerular and tubular diseases. Translational approaches could be facilitated by
      the development of effective inhibitors of specific miRs and methods for optimal
      delivery of anti-miRs to the kidney. The major goal of this review is to
      highlight key functions of these miRs and their relationships to human diseases,
      with special emphasis on diabetic kidney disease.

PMID- 19581406
TI  - Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide.
AB  - Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the
      host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and
      related Actinomycetes convert their MDP to an N-glycolylated form through the
      action of N-acetyl muramic acid hydroxylase (NamH). We used a combination of
      bacterial genetics and synthetic chemistry to investigate whether N-glycolylation
      of MDP alters NOD2-mediated immunity. Upon infecting macrophages with 12
      bacteria, tumor necrosis factor (TNF) alpha secretion was NOD2 dependent only
      with mycobacteria and other Actinomycetes (Nocardia and Rhodococcus). Disruption
      of namH in Mycobacterium smegmatis obrogated NOD2-mediated TNF secretion, which
      could be restored upon gene complementation. In mouse macrophages, N-glycolyl MDP
      was more potent than N-acetyl MDP at activating RIP2, nuclear factor kappaB, c
      Jun N-terminal kinase, and proinflammatory cytokine secretion. In mice challenged
      intraperitoneally with live or killed mycobacteria, NOD2-dependent immune
      responses depended on the presence of bacterial namH. Finally, N-glycolyl MDP was
      more efficacious than N-acetyl MDP at inducing ovalbumin-specific T cell immunity
      in a model of adjuvancy. Our findings indicate that N-glycolyl MDP has a greater
      NOD2-stimulating activity than N-acetyl MDP, consistent with the historical
      observation attributing exceptional immunogenic activity to the mycobacterial
      cell wall.

PMID- 19581407
TI  - Blockade of CTLA-4 on both effector and regulatory T cell compartments
      contributes to the antitumor activity of anti-CTLA-4 antibodies.
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical negative
      regulator of immune responses. Uniquely among known inhibitory receptors, its
      genetic ablation results in a fulminating and fatal lymphoproliferative disorder.
      This central regulatory role led to the development of antibodies designed to
      block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer.
      Despite their preclinical efficacy and promising clinical activity against late
      stage metastatic melanoma, the critical cellular targets for their activity
      remains unclear. In particular, debate has focused on whether the effector T cell
      (T(eff)) or regulatory T cell (T reg cell) compartment is the primary target of
      antibody-mediated blockade. We developed a mouse expressing human instead of
      mouse CTLA-4, allowing us to evaluate the independent contributions of CTLA-4
      blockade of each T cell compartment during cancer immunotherapy in an in vivo
      model of mouse melanoma. The data show that although blockade on effector cells
      significantly improves tumor protection, unicompartmental blockade on regulatory
      cells completely fails to enhance antitumor responses. However, concomitant
      blockade of both compartments leads to a synergistic effect and maximal antitumor
      activity. We conclude that the combination of direct enhancement of T(eff) cell
      function and concomitant inhibition of T reg cell activity through blockade of
      CTLA-4 on both cell types is essential for mediating the full therapeutic effects
      of anti-CTLA-4 antibodies during cancer immunotherapy.

PMID- 19581408
TI  - NF-kappaB activity marks cells engaged in receptor editing.
AB  - Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms
      are necessary to ensure that B cells do not respond to self-antigens. One such
      tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on
      an immature B cell recognizes self-antigen, it is down-regulated from the cell
      surface, and light chain gene rearrangement continues in an attempt to edit the
      autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF
      kappaB-dependent IkappaB alpha gene was replaced with a lacZ (beta-gal) reporter
      complementary DNA (cDNA; IkappaB alpha(+/lacZ)) suggests a potential role for NF
      kappaB in receptor editing. Sorted beta-gal(+) pre-B cells showed increased
      levels of various markers of receptor editing. In IkappaB alpha(+/lacZ) reporter
      mice expressing either innocuous or self-specific knocked in BCRs, beta-gal was
      preferentially expressed in pre-B cells from the mice with self-specific BCRs.
      Retroviral-mediated expression of a cDNA encoding an IkappaB alpha superrepressor
      in primary bone marrow cultures resulted in diminished germline kappa and
      rearranged lambda transcripts but similar levels of RAG expression as compared
      with controls. We found that IRF4 transcripts were up-regulated in beta-gal(+)
      pre-B cells. Because IRF4 is a target of NF-kappaB and is required for receptor
      editing, we suggest that NF-kappaB could be acting through IRF4 to regulate
      receptor editing.

PMID- 19581409
TI  - Suppression of RhoG activity is mediated by a syndecan 4-synectin-RhoGDI1 complex
      and is reversed by PKCalpha in a Rac1 activation pathway.
AB  - Fibroblast growth factor 2 (FGF2) is a major regulator of developmental,
      pathological, and therapeutic angiogenesis. Its activity is partially mediated by
      binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires
      polarized activation of the small guanosine triphosphatase Rac1, which involves
      localized dissociation from RhoGDI1 and association with the plasma membrane.
      Previous work has shown that genetic deletion of S4 or its adapter, synectin,
      leads to depolarized Rac activation, decreased endothelial migration, and other
      physiological defects. In this study, we show that Rac1 activation downstream of
      S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive
      state by RhoGDI1, which is found in a ternary complex with synectin and S4.
      Binding of S4 to synectin increases the latter's binding to RhoGDI1, which in
      turn enhances RhoGDI1's affinity for RhoG. S4 clustering activates PKCalpha,
      which phosphorylates RhoGDI1 at Ser(96). This phosphorylation triggers release of
      RhoG, leading to polarized activation of Rac1. Thus, FGF2-induced Rac1 activation
      depends on the suppression of RhoG by a previously uncharacterized ternary S4
      synectin-RhoGDI1 protein complex and activation via PKCalpha.

PMID- 19581410
TI  - Synchronizing chromosome segregation by flux-dependent force equalization at
      kinetochores.
AB  - The synchronous movement of chromosomes during anaphase ensures their correct
      inheritance in every cell division. This reflects the uniformity of spindle
      forces acting on chromosomes and their simultaneous entry into anaphase. Although
      anaphase onset is controlled by the spindle assembly checkpoint, it remains
      unknown how spindle forces are uniformly distributed among different chromosomes.
      In this paper, we show that tension uniformity at metaphase kinetochores and
      subsequent anaphase synchrony in Drosophila S2 cells are promoted by spindle
      microtubule flux. These results can be explained by a mechanical model of the
      spindle where microtubule poleward translocation events associated with flux
      reflect relaxation of the kinetochore-microtubule interface, which accounts for
      the redistribution and convergence of kinetochore tensions in a timescale
      comparable to typical metaphase duration. As predicted by the model, experimental
      acceleration of mitosis precludes tension equalization and anaphase synchrony. We
      propose that flux-dependent equalization of kinetochore tensions ensures a timely
      and uniform maturation of kinetochore-microtubule interfaces necessary for error
      free and coordinated segregation of chromosomes in anaphase.

PMID- 19581413
TI  - HIV, prayer, and vintage cars: Danny Douek talks shop.

PMID- 19581411
TI  - Organelle tethering by a homotypic PDZ interaction underlies formation of the
      Golgi membrane network.
AB  - Formation of the ribbon-like membrane network of the Golgi apparatus depends on
      GM130 and GRASP65, but the mechanism is unknown. We developed an in vivo
      organelle tethering assaying in which GRASP65 was targeted to the mitochondrial
      outer membrane either directly or via binding to GM130. Mitochondria bearing
      GRASP65 became tethered to one another, and this depended on a GRASP65 PDZ domain
      that was also required for GRASP65 self-interaction. Point mutation within the
      predicted binding groove of the GRASP65 PDZ domain blocked both tethering and, in
      a gene replacement assay, Golgi ribbon formation. Tethering also required
      proximate membrane anchoring of the PDZ domain, suggesting a mechanism that
      orientates the PDZ binding groove to favor interactions in trans. Thus, a
      homotypic PDZ interaction mediates organelle tethering in living cells.

PMID- 19581412
TI  - Quantitative proteomics identifies a Dab2/integrin module regulating cell
      migration.
AB  - Clathrin-associated endocytic adapters recruit cargoes to coated pits as a first
      step in endocytosis. We developed an unbiased quantitative proteomics approach to
      identify and quantify glycoprotein cargoes for an endocytic adapter, Dab2.
      Surface levels of integrins beta1, alpha1, alpha2, and alpha3 but not alpha5 or
      alphav chains were specifically increased on Dab2-deficient HeLa cells. Dab2
      colocalizes with integrin beta1 in coated pits that are dispersed over the cell
      surface, suggesting that it regulates bulk endocytosis of inactive integrins.
      Depletion of Dab2 inhibits cell migration and polarized movement of integrin
      beta1 and vinculin to the leading edge. By manipulating intracellular and surface
      integrin beta1 levels, we show that migration speed correlates with the
      intracellular integrin pool but not the surface level. Together, these results
      suggest that Dab2 internalizes integrins freely diffusing on the cell surface and
      that Dab2 regulates migration, perhaps by maintaining an internal pool of
      integrins that can be recycled to create new adhesions at the leading edge.

PMID- 19581414
TI  - Islet beta-cells deficient in Bcl-xL develop but are abnormally sensitive to
      apoptotic stimuli.
AB  - OBJECTIVE: Bcl-xL is an antiapoptotic member of the Bcl-2 family of proteins and
      a potent regulator of cell death. We investigated the importance of Bcl-xL for
      beta-cells by deleting the Bcl-x gene specifically in beta-cells and analyzing
      their survival in vivo and in culture. RESEARCH DESIGN AND METHODS: Islets with
      beta-cells lacking the Bcl-x gene were assessed in vivo by histology and by
      treatment of mice with low-dose streptozotocin (STZ). Islets were isolated by
      collagenase digestion and treated in culture with the apoptosis inducers
      staurosporine, thapsigargin, gamma-irradiation, proinflammatory cytokines, or Fas
      ligand. Cell death was assessed by flow cytometric analysis of subgenomic DNA.
      RESULTS: Bcl-xL-deficient beta-cells developed but were abnormally sensitive to
      apoptosis induced in vivo by low-dose STZ. Although a small proportion of beta
      cells still expressed Bcl-xL, these did not have a survival advantage over their
      Bcl-xL-deficient neighbors. Islets appeared normal after collagenase isolation
      and whole-islet culture. They were, however, abnormally sensitive in culture to a
      number of different apoptotic stimuli including cytotoxic drugs, proinflammatory
      cytokines, and Fas ligand. CONCLUSIONS: Bcl-xL expression in beta-cells is
      dispensible during islet development in the mouse. Bcl-xL is, however, an
      important regulator of beta-cell death under conditions of synchronous stress.
      Bcl-xL expression at physiological levels may partially protect beta-cells from
      apoptotic stimuli, including apoptosis because of mediators implicated in type 1
      diabetes and death or degeneration of transplanted islets.

PMID- 19581415
TI  - Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling.
AB  - OBJECTIVE: Recent data demonstrated that glucose sensing in different tissues is
      initiated by an intracellular redox signaling pathway in physiological
      conditions. However, the relevance of such a mechanism in metabolic disease is
      not known. The aim of the present study was to determine whether brain glucose
      hypersensitivity present in obese Zucker rats is related to an alteration in
      redox signaling. RESEARCH DESIGN AND METHODS: Brain glucose sensing alteration
      was investigated in vivo through the evaluation of electrical activity in arcuate
      nucleus, changes in reactive oxygen species levels, and hypothalamic glucose
      induced insulin secretion. In basal conditions, modifications of redox state and
      mitochondrial functions were assessed through oxidized glutathione, glutathione
      peroxidase, manganese superoxide dismutase, aconitase activities, and
      mitochondrial respiration. RESULTS: Hypothalamic hypersensitivity to glucose was
      characterized by enhanced electrical activity of the arcuate nucleus and
      increased insulin secretion at a low glucose concentration, which does not
      produce such an effect in normal rats. It was associated with 1) increased
      reactive oxygen species levels in response to this low glucose load, 2)
      constitutive oxidized environment coupled with lower antioxidant enzyme activity
      at both the cellular and mitochondrial level, and 3) overexpression of several
      mitochondrial subunits of the respiratory chain coupled with a global dysfunction
      in mitochondrial activity. Moreover, pharmacological restoration of the
      glutathione hypothalamic redox state by reduced glutathione infusion in the third
      ventricle fully reversed the cerebral hypersensitivity to glucose. CONCLUSIONS:
      The data demonstrated that obese Zucker rats' impaired hypothalamic regulation in
      terms of glucose sensing is linked to an abnormal redox signaling, which
      originates from mitochondria dysfunction.

PMID- 19581416
TI  - TIMP3 is reduced in atherosclerotic plaques from subjects with type 2 diabetes
      and increased by SirT1.
AB  - OBJECTIVE: Atherosclerosis is accelerated in subjects with type 2 diabetes by
      unknown mechanisms. We identified tissue inhibitor of metalloproteinase 3
      (TIMP3), the endogenous inhibitor of A disintegrin and metalloprotease domain 17
      (ADAM17) and other matrix metalloproteinases (MMPs), as a gene modifier for
      insulin resistance and vascular inflammation in mice. We tested its association
      with atherosclerosis in subjects with type 2 diabetes and identified Sirtuin 1
      (SirT1) as a major regulator of TIMP3 expression. RESEARCH DESIGN AND METHODS: We
      investigated ADAM10, ADAM17, MMP9, TIMP1, TIMP2, TIMP3, and TIMP4 expression
      levels in human carotid atherosclerotic plaques (n = 60) from subjects with and
      without diabetes. Human vascular smooth muscle cells exposed to several metabolic
      stimuli were used to identify regulators of TIMP3 expression. SirT1 small
      interference RNA, cDNA, and TIMP3 promoter gene reporter were used to study SirT1
      dependent regulation of TIMP3. RESULTS: Here, we show that in human carotid
      atherosclerotic plaques, TIMP3 was significantly reduced in subjects with type 2
      diabetes, leading to ADAM17 and MMP9 overactivity. Reduced expression of TIMP3
      was associated in vivo with SirT1 levels. In smooth muscle cells, inhibition of
      SirT1 activity and levels reduced TIMP3 expression, whereas SirT1 overexpression
      increased TIMP3 promoter activity. CONCLUSIONS: In atherosclerotic plaques from
      subjects with type 2 diabetes, the deregulation of ADAM17 and MMP9 activities is
      related to inadequate expression of TIMP3 via SirT1. Studies in vascular cells
      confirmed the role of SirT1 in tuning TIMP3 expression.

PMID- 19581417
TI  - Gene profiling of human adipose tissue during evoked inflammation in vivo.
AB  - OBJECTIVE: Adipose inflammation plays a central role in obesity-related metabolic
      and cardiovascular complications. However, few human adipose-secreted proteins
      are known to mediate these processes. We hypothesized that microarray mRNA
      profiling of human adipose during evoked inflammation could identify novel
      adipocytokines. RESEARCH DESIGN AND METHODS: Healthy human volunteers (n = 14)
      were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and
      underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix
      U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were
      selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode
      secreted proteins. Of these, 86 candidates were chosen for validation in adipose
      from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and
      for exploration of cellular origin in primary human adipocytes and macrophages in
      vitro. RESULTS: Microarray identified 776 adipose genes modulated by LPS; 298
      were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96%
      [95% CI 90-99]) were upregulated (fold changes >1.0) during the lower-dose (LPS
      0.6 ng/kg) validation study and 51 of 85 (59% [49-70]) were induced greater than
      1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to
      M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73% of
      detectable genes, respectively. CONCLUSIONS: We demonstrate that evoked
      inflammation of human adipose in vivo modulated expression of multiple genes
      likely secreted by adipocytes and monocytes. These included established
      adipocytokines and chemokines implicated in recruitment and activation of
      lymphocytes, adhesion molecules, antioxidants, and several novel genes with
      unknown function. Such candidates may represent biomarkers and therapeutic
      targets for obesity-related complications.

PMID- 19581420
TI  - Prediction of metabolic syndrome by low serum testosterone levels in men: results
      from the study of health in Pomerania.
AB  - OBJECTIVE: The aim of this analysis was to assess the prospective association of
      serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with
      incident metabolic syndrome (MetS) in men. RESEARCH DESIGN AND METHODS: Data were
      obtained from the Study of Health in Pomerania (SHIP), a population-based
      prospective cohort of adults aged 20-79 years. Analyses were conducted in 1,004
      men without baseline MetS defined by National Cholesterol Education Program Adult
      Treatment Panel III guidelines. Testosterone and DHEAS were categorized by age
      specific quartiles and Poisson regression models with relative risks (RRs) and
      95% CIs were estimated. RESULTS: After a median follow-up time of 5.0 years, 480
      men (47.8%) developed MetS. Testosterone levels decreased with increasing number
      of MetS components. Testosterone in the lowest quartile predicted MetS (RR 1.38
      [95% CI 1.13-1.69]), particularly among men aged 20-39 years (2.06 [1.29-3.29]),
      even after adjustment for age, smoking, alcohol consumption, physical activity,
      waist circumference, self-related health, and time of blood sampling. DHEAS
      levels were not related to incident MetS (0.99 [0.83-1.19]). CONCLUSIONS: Low
      testosterone but not DHEAS predicts development of MetS in a population-based
      cohort of 1,004 men aged 20-79 years. Especially in young men aged 20-39 years,
      results suggest low testosterone as a strong predictor for incident MetS.
      Assessment of testosterone in young and middle-age men may allow early
      interventions in the general population.

PMID- 19581419
TI  - Mitochondrial networking protects beta-cells from nutrient-induced apoptosis.
AB  - OBJECTIVE: Previous studies have reported that beta-cell mitochondria exist as
      discrete organelles that exhibit heterogeneous bioenergetic capacity. To date,
      networking activity, and its role in mediating beta-cell mitochondrial morphology
      and function, remains unclear. In this article, we investigate beta-cell
      mitochondrial fusion and fission in detail and report alterations in response to
      various combinations of nutrients. RESEARCH DESIGN AND METHODS: Using matrix
      targeted photoactivatable green fluorescent protein, mitochondria were tagged and
      tracked in beta-cells within intact islets, as isolated cells and as cell lines,
      revealing frequent fusion and fission events. Manipulations of key mitochondrial
      dynamics proteins OPA1, DRP1, and Fis1 were tested for their role in beta-cell
      mitochondrial morphology. The combined effects of free fatty acid and glucose on
      beta-cell survival, function, and mitochondrial morphology were explored with
      relation to alterations in fusion and fission capacity. RESULTS: beta-Cell
      mitochondria are constantly involved in fusion and fission activity that
      underlies the overall morphology of the organelle. We find that networking
      activity among mitochondria is capable of distributing a localized green
      fluorescent protein signal throughout an isolated beta-cell, a beta-cell within
      an islet, and an INS1 cell. Under noxious conditions, we find that beta-cell
      mitochondria become fragmented and lose their ability to undergo fusion.
      Interestingly, manipulations that shift the dynamic balance to favor fusion are
      able to prevent mitochondrial fragmentation, maintain mitochondrial dynamics, and
      prevent apoptosis. CONCLUSIONS: These data suggest that alterations in
      mitochondrial fusion and fission play a critical role in nutrient-induced beta
      cell apoptosis and may be involved in the pathophysiology of type 2 diabetes.

PMID- 19581418
TI  - Increased MAPK activation and impaired insulin signaling in subcutaneous
      microvascular endothelial cells in type 2 diabetes: the role of endothelin-1.
AB  - OBJECTIVE: To establish a method for isolation and culture of subcutaneous
      microvascular endothelial cells (MVEC) from small human tissue biopsies to
      compare gene and protein expression of insulin signaling molecules in MVEC from
      insulin-resistant and healthy control subjects. RESEARCH DESIGN AND METHODS:
      Stromavascular cells from subcutaneous needle biopsies of type 2 diabetic and
      control subjects were expanded in culture and the endothelial cells selected with
      magnetic immune separation. Western blots and RT-PCR were used for protein and
      gene expression assays. RESULTS: At least 99% of the expanded primary MVEC could
      be characterized as endothelial cells. The expression of insulin receptors was
      low, but insulin increased tyrosine phosphorylation of both the insulin receptor
      and insulin receptor substrate (IRS)-1 and activated protein kinase B (PKB). The
      IRS-1 protein expression was reduced and the serine phosphorylation of PKB in
      response to insulin attenuated whereas basal and insulin-stimulated
      phosphorylation of extracellular signal-related kinase (ERK)1/2 was increased in
      type 2 diabetes MVEC. Endothelin (ET)-1 mRNA levels were significantly higher in
      type 2 diabetes cells. The addition of ET-1 increased the phosphorylation of
      mitogen-activated protein kinase (MAPK), an effect antagonized by the MEK-1
      inhibitor PD98059. Furthermore, the endothelin ET(A) and ET(B) receptor
      antagonists BQ123 and BQ788 decreased basal MAPK activity in type 2 diabetes MVEC
      and prevented the ET-1-induced activation. CONCLUSIONS: We developed a system for
      isolation and culture of human MVEC from small needle biopsies. Our observations
      support the concept of "selective" insulin resistance, involving IRS-1 and the
      PI3kinase pathway, as an underlying factor for a dysregulated microvascular
      endothelium in type 2 diabetes. Our data also support a role of ET-1 for the
      increased MAPK activity seen in nonstimulated type 2 diabetes MVEC.

PMID- 19581421
TI  - Intramuscular lipid metabolism in the insulin resistance of smoking.
AB  - OBJECTIVE: Smoking decreases insulin action and increases the risk of type 2
      diabetes in humans. Mechanisms responsible for smoking-induced insulin resistance
      are unclear. We hypothesized smokers would have increased intramuscular
      triglyceride (IMTG) and diacylglycerol (DAG) concentration and decreased
      fractional synthesis rate (FSR) compared with nonsmokers. RESEARCH DESIGN AND
      METHODS: Nonsmokers (n = 18, aged 20 +/- 0.5 years, BMI 22 +/- 0.4 kg/m(2), body
      fat 20 +/- 2%, 0 cigarettes per day) and smokers (n = 14, aged 21 +/- 0.7 years,
      BMI 23 +/- 0.4 kg/m(2), body fat 20 +/- 3%, 18 +/- 0.7 cigarettes per day) were
      studied in a fasted condition after a standardized diet. [U-(13)C]palmitate was
      infused during 4 h of rest followed by a skeletal muscle biopsy and intravenous
      glucose tolerance test. RESULTS: Smokers were less insulin sensitive (S(i))
      compared with nonsmokers (S(i) 5.28 +/- 0.5 nonsmokers vs. 3.74 +/- 0.3 smokers
      10(-4) x microU(-1) x ml(-1), P = 0.03). There were no differences in IMTG or DAG
      concentration (IMTG 24.2 +/- 3.4 nonsmokers vs. 27.2 +/- 5.9 smokers microg/mg
      dry wt, DAG 0.34 +/- 0.02 nonsmokers vs. 0.35 +/- 0.02 smokers microg/mg dry wt)
      or IMTG FSR between groups (0.66 +/- 0.1 nonsmokers vs. 0.55 +/- 0.09 smokers
      %/hr). Intramuscular lipid composition was different, with increased percent
      saturation of IMTG (32.1 +/- 1.2 nonsmokers vs. 35.2 +/- 1.0 smokers %, P = 0.05)
      and DAG (52.8 +/- 1.7 nonsmokers vs. 58.8 +/- 2.2 smokers %, P = 0.04) in
      smokers. Smokers had significantly decreased peroxisome proliferator-activated
      receptor-gamma (1.76 +/- 0.1 nonsmokers vs. 1.42 +/- 0.11 smokers arbitrary units
      [AU], P = 0.03) and increased monocyte chemotactic protein-1 (3.11 +/- 0.41
      nonsmokers vs. 4.83 +/- 0.54 smokers AU, P = 0.02) mRNA expression compared with
      nonsmokers. We also found increased insulin receptor substrate-1 Ser(636)
      phosphorylation in smokers compared with nonsmokers (0.73 +/- 0.08 nonsmokers vs.
      1.14 +/- 0.09 smokers AU, P = 0.002). CONCLUSIONS: These data suggest: 1) IMTG
      concentration and turnover are not related to alterations in insulin action in
      smokers compared to nonsmokers, 2) increased saturation of IMTG and DAG in
      skeletal muscle may be related to insulin action, and 3) basal inhibition of
      insulin receptor substrate-1 may decrease insulin action in smokers.

PMID- 19581422
TI  - Systemic fate of the adipocyte-derived factor adiponectin.
AB  - OBJECTIVE: The adipocyte-derived secretory protein adiponectin has been widely
      studied and shown to have potent insulin-sensitizing, antiapoptotic, and anti
      inflammatory properties. While its biosynthesis is well understood, its fate,
      once in circulation, is less well established. RESEARCH DESIGN AND METHODS: Here,
      we examine the half-life of adiponectin in circulation by tracking fluorescently
      labeled recombinant adiponectin in the circulation, following it to its final
      destination in the hepatocyte. RESULTS: Despite its abundant presence in plasma,
      adiponectin is cleared rapidly with a half-life of approximately 75 min. A more
      bioactive version carrying a mutation at cysteine 39 is cleared within minutes.
      Even though steady-state levels of adiponectin differ between male and female
      mice, we failed to detect any differences in clearance rates, suggesting that
      differences in plasma are mostly due to differential production rates. In a
      metabolically challenged state (high-fat diet exposure or in an ob/ob
      background), adiponectin levels are reduced in plasma and clearance is
      significantly prolonged, reflecting a dramatic drop in adiponectin production
      levels. CONCLUSIONS: Combined, these results show a surprisingly rapid turnover
      of adiponectin with multiple fat pads contributing to the plasma levels of
      adiponectin and clearance mediated primarily by the liver. It is surprising that
      despite high-level production and rapid clearance, plasma levels of adiponectin
      remain remarkably constant.

PMID- 19581424
TI  - Alcohol consumption and health status in older adults: a longitudinal analysis.
AB  - Objective. This longitudinal study examines the relationship of alcohol
      consumption to mortality and changes in mental and functional health in older
      adults. Method.In a national population health survey, 4,187 participants aged 50
      and older at baseline provided information on alcohol consumption, potential
      confounders, and follow-up vital status. Logistic regression estimated the odds
      ratio for mortality, increase in psychological distress, and decline in
      functional health 10 years later. Results. Compared with lifelong abstainers,
      light and moderate drinkers were at nonsignificantly lower risk of mortality.
      Among survivors, alcohol consumption showed no consistent relationship with
      increases in psychological distress. Occasional and light drinkers had
      significantly reduced risk of a substantial functional health decline, whereas
      moderate drinkers had nonsignificantly reduced risk. Discussion. Findings suggest
      that light-to-moderate alcohol consumption reduces the risk of substantial
      functional health decline in older middle-aged drinkers.

PMID- 19581423
TI  - The C3a anaphylatoxin receptor is a key mediator of insulin resistance and
      functions by modulating adipose tissue macrophage infiltration and activation.
AB  - OBJECTIVE: Significant new data suggest that metabolic disorders such as
      diabetes, obesity, and atherosclerosis all posses an important inflammatory
      component. Infiltrating macrophages contribute to both tissue-specific and
      systemic inflammation, which promotes insulin resistance. The complement cascade
      is involved in the inflammatory cascade initiated by the innate and adaptive
      immune response. A mouse genomic F2 cross biology was performed and identified
      several causal genes linked to type 2 diabetes, including the complement pathway.
      RESEARCH DESIGN AND METHODS: We therefore sought to investigate the effect of a
      C3a receptor (C3aR) deletion on insulin resistance, obesity, and macrophage
      function utilizing both the normal-diet (ND) and a diet-induced obesity mouse
      model. RESULTS: We demonstrate that high C3aR expression is found in white
      adipose tissue and increases upon high-fat diet (HFD) feeding. Both adipocytes
      and macrophages within the white adipose tissue express significant amounts of
      C3aR. C3aR(-/-) mice on HFD are transiently resistant to diet-induced obesity
      during an 8-week period. Metabolic profiling suggests that they are also
      protected from HFD-induced insulin resistance and liver steatosis. C3aR(-/-) mice
      had improved insulin sensitivity on both ND and HFD as seen by an insulin
      tolerance test and an oral glucose tolerance test. Adipose tissue analysis
      revealed a striking decrease in macrophage infiltration with a concomitant
      reduction in both tissue and plasma proinflammatory cytokine production.
      Furthermore, C3aR(-/-) macrophages polarized to the M1 phenotype showed a
      considerable decrease in proinflammatory mediators. CONCLUSIONS: Overall, our
      results suggest that the C3aR in macrophages, and potentially adipocytes, plays
      an important role in adipose tissue homeostasis and insulin resistance.

PMID- 19581425
TI  - An exploratory study of individual and environmental correlates of fear of
      falling among community-dwelling seniors.
AB  - Objectives. The objective of this study was to identify individual and
      environmental correlates of fear of falling among community-dwelling seniors.
      Method. The study sample involved 288 community-dwelling adults aged 65 years or
      older going through the normal aging process. Fear of falling and a series of
      individual and environmental characteristics were measured with a questionnaire
      during home interviews. Results. Multivariate logistic regression procedures
      showed that the strongest correlates of fear of falling are gender, support from
      a spouse or partner, and residential area. Being a female as well as living in a
      smaller city or rural area were shown to be risk factors for fear of falling,
      whereas the availability of support from a spouse or partner was a protective
      factor. Discussion. Findings from this study suggest that researchers should
      adopt an ecological perspective to understanding the phenomenon of fear of
      falling among seniors and collect data on a broader range of individual and
      environmental factors.

PMID- 19581426
TI  - Stability of intramolecular quadruplexes: sequence effects in the central loop.
AB  - Hundreds of thousands of putative quadruplex sequences have been found in the
      human genome. It is important to understand the rules that govern the stability
      of these intramolecular structures. In this report, we analysed sequence effects
      in a 3-base-long central loop, keeping the rest of the quadruplex unchanged. A
      first series of 36 different sequences were compared; they correspond to the
      general formula GGGTTTGGGHNHGGGTTTGGG. One clear rule emerged from the comparison
      of all sequence motifs: the presence of an adenine at the first position of the
      loop was significantly detrimental to stability. In contrast, adenines have no
      detrimental effect when present at the second or third position of the loop.
      Cytosines may either have a stabilizing or destabilizing effect depending on
      their position. In general, the correlation between the T(m) or DeltaG degrees in
      sodium and potassium was weak. To determine if these sequence effects could be
      generalized to different quadruplexes, specific loops were tested in different
      sequence contexts. Analysis of 26 extra sequences confirmed the general
      destabilizing effect of adenine as the first base of the loop(s). Finally,
      analysis of some of the sequences by microcalorimetry (DSC) confirmed the
      differences found between the sequence motifs.

PMID- 19581428
TI  - How safe are trick-or-treaters? An analysis of child sex crime rates on
      halloween.
AB  - States, municipalities, and parole departments have adopted policies banning
      known sex offenders from Halloween activities, based on the worry that there is
      unusual risk on these days. The existence of this risk has not been empirically
      established. National Incident-Base Reporting System crime report data from 1997
      through 2005 were used to examine daily population adjusted rates from 67,045
      nonfamilial sex crimes against children aged 12 years and less. Halloween rates
      were compared with expectations based on time, seasonality, and weekday
      periodicity. Rates did not differ from expectation, no increased rate on or just
      before Halloween was found, and Halloween incidents did not evidence unusual case
      characteristics. Findings were invariant across years, both prior to and after
      these policies became popular. These findings raise questions about the wisdom of
      diverting law enforcement resources to attend to a problem that does not appear
      to exist.

PMID- 19581429
TI  - Fathers, physical child abuse, and neglect: advancing the knowledge base.
AB  - Fathers are overrepresented as perpetrators of physical child maltreatment,
      particularly in its most severe forms. Despite this, the research literature
      continues to lack specificity regarding the role fathers play in risk for
      physical child abuse or neglect (PCAN). Furthermore, although fathers have
      received more attention with respect to child sexual abuse and its treatment,
      their influence has been largely disregarded in many intervention efforts to
      reduce PCAN. Inadequate attention to the role of fathers, both in research and
      practice, has numerous problematic implications for the prevention of child
      maltreatment. The goal of this special issue is to disseminate new research that
      examines fathers' roles by focusing on multiple fathering factors that may
      directly and indirectly shape both maternal and paternal risk of engaging in
      PCAN. In the introduction to the special issue, we highlight key questions in the
      research literature and present our perspective on how the articles included in
      this special issue address some of these gaps.

PMID- 19581427
TI  - Integrated study of copy number states and genotype calls using high-density SNP
      arrays.
AB  - We propose a statistical framework, named genoCN, to simultaneously dissect copy
      number states and genotypes using high-density SNP (single nucleotide
      polymorphism) arrays. There are at least two types of genomic DNA copy number
      differences: copy number variations (CNVs) and copy number aberrations (CNAs).
      While CNVs are naturally occurring and inheritable, CNAs are acquired somatic
      alterations most often observed in tumor tissues only. CNVs tend to be short and
      more sparsely located in the genome compared with CNAs. GenoCN consists of two
      components, genoCNV and genoCNA, designed for CNV and CNA studies, respectively.
      In contrast to most existing methods, genoCN is more flexible in that the model
      parameters are estimated from the data instead of being decided a priori. GenoCNA
      also incorporates two important strategies for CNA studies. First, the effects of
      tissue contamination are explicitly modeled. Second, if SNP arrays are performed
      for both tumor and normal tissues of one individual, the genotype calls from
      normal tissue are used to study CNAs in tumor tissue. We evaluated genoCN by
      applications to 162 HapMap individuals and a brain tumor (glioblastoma) dataset
      and showed that our method can successfully identify both types of copy number
      differences and produce high-quality genotype calls.

PMID- 19581430
TI  - Fathering by partner-abusive men: attitudes on children's exposure to
      interparental conflict and risk factors for child abuse.
AB  - A substantial body of research concludes that children in homes marked by
      intimate partner violence (IPV) and conflict are at increased risk for
      maladjustment. Although studies often attribute these difficulties to the
      aggressive acts witnessed, other research and theoretical work suggests that
      disrupted parenting and co-occurring child maltreatment play an equally critical
      role in the onset of the children's psychological and behavioral problems.
      Despite the clear importance of parenting in the context of IPV, relatively
      little scholarship has been devoted to the topic, particularly when it comes to
      examining fathers. The current study sought to better understand the paternal
      relationships of men arrested for spouse/partner abuse, to examine their beliefs
      about children's exposure to interparental conflict and to identify the specific
      factors that may place their children at risk for maltreatment. The data
      consisted of questionnaires administered to 3,824 men attending a court-ordered
      evaluation after they were convicted of assaulting an intimate partner. Analyses
      revealed that most of the men had some type of fathering role with underage
      children (n = 2,508; 65.6%) and in most cases these relationships continued
      following their arrest. Although the majority of the men acknowledged that their
      children had been exposed to interparental conflicts, few perceived that their
      children had been affected by the arguing. Also of concern was the fact that risk
      factors for child maltreatment were highly prevalent in this population.
      Implications of these findings and suggestions for those working with domestic
      offenders are discussed.

PMID- 19581431
TI  - Mothers, men, and child protective services involvement.
AB  - This study used data on 2,297 families from the Fragile Families and Child
      Wellbeing Study to examine whether Child Protective Services (CPS) involvement
      varies by maternal relationship status. Families were categorized according to
      whether the mother was living with a (male) partner or spouse, was involved in a
      dating relationship, or was not romantically involved. Families in which the
      mother was romantically involved were further delineated by whether her partner
      was the biological father of none, some, or all of the children in her household.
      Results indicated that families in which the mother was living with a man who was
      not the biological father of all children and those in which she was not
      romantically involved were significantly more likely to be contacted by CPS than
      those in which she was living with the biological father of all resident
      children. These findings withstood the inclusion of detailed controls for the
      mother's characteristics and behaviors and (in two-parent families) her partner's
      characteristics and behaviors, suggesting that they are not fully explained by
      observable social selection factors.

PMID- 19581433
TI  - Commentary on fathers and children and maltreatment: relationships matter most.

PMID- 19581432
TI  - Fathers and maternal risk for physical child abuse.
AB  - This study set out to examine father-related factors predicting maternal physical
      child abuse risk in a national birth cohort of 1,480 families. In-home and phone
      interviews were conducted with mothers when index children were 3 years old.
      Predictor variables included the mother-father relationship status; father
      demographic, economic, and psychosocial variables; and key background factors.
      Outcome variables included both observed and self-reported proxies of maternal
      physical child abuse risk. At the bivariate level, mothers married to fathers
      were at lower risk for most indicators of maternal physical child abuse. However,
      after accounting for specific fathering factors and controlling for background
      variables, multivariate analyses indicated that marriage washed out as a
      protective factor, and on two of three indicators was linked with greater
      maternal physical abuse risk. Regarding fathering factors linked with risk,
      fathers' higher educational attainment and their positive involvement with their
      children most discernibly predicted lower maternal physical child abuse risk.
      Fathers' economic factors played no observable role in mothers' risk for physical
      child maltreatment. Such multivariate findings suggest that marriage per se does
      not appear to be a protective factor for maternal physical child abuse and rather
      it may serve as a proxy for other father-related protective factors.

PMID- 19581434
TI  - A prototype analysis of gratitude: varieties of gratitude experiences.
AB  - The present research tested the hypothesis that concepts of gratitude are
      prototypically organized and explored whether lay concepts of gratitude are
      broader than researchers' concepts of gratitude. In five studies, evidence was
      found that concepts of gratitude are indeed prototypically organized. In Study 1,
      participants listed features of gratitude. In Study 2, participants reliably
      rated the centrality of these features. In Studies 3a and 3b, participants
      perceived that a hypothetical other was experiencing more gratitude when they
      read a narrative containing central as opposed to peripheral features. In Study
      4, participants remembered more central than peripheral features in gratitude
      narratives. In Study 5a, participants generated more central than peripheral
      features when they wrote narratives about a gratitude incident, and in Studies 5a
      and 5b, participants generated both more specific and more generalized types of
      gratitude in similar narratives. Throughout, evidence showed that lay conceptions
      of gratitude are broader than current research definitions.

PMID- 19581435
TI  - Living together apart: perceived concealment as a signal of exclusion in marital
      relationships.
AB  - This article examines how perceiving concealment in close relationships
      influences marital well-being. It suggests that the perception of concealment
      from a partner signals separateness from one's partner and contributes to
      feelings of perceived partner exclusion. These feelings of exclusion, in turn,
      should negatively affect relational quality. These predictions are tested in a
      prospective study among 199 newlywed couples. Results suggest that perceiving
      concealment reduced marital adjustment and trust and increased conflict over
      time. Importantly, change in perceived partner exclusion mediated these effects.
      This article demonstrates that the perception of concealment (a) has deleterious
      effects on relational well-being in the long run and (b) is harmful in part
      because it elicits feelings of exclusion.

PMID- 19581436
TI  - Playing favorites: the influence of leaders' inner circle on group processes and
      performance.
AB  - Leaders frequently form stronger relationships with certain subordinates moreso
      than others, creating an inner circle of close friendships and an outer circle of
      more distant relationships. Three studies examine the effects of inner-circle
      membership on group dynamics and interpersonal influence in hierarchical teams.
      Study 1 finds that, compared to outer-circle members, inner-circle members feel
      safer and participate in the group discussion more, and leaders recognize them as
      making a greater contribution and allocate a larger bonus to them. Consequently,
      inner-circle members influence the groups' decisions more, and team decision
      quality improves when inner-circle members possess expert knowledge. Study 2
      finds that leaders attended to and recalled suggestions from their inner circle
      more regardless of argument strength, suggesting heuristic information
      processing. Study 3 replicates these findings using intact teams in a large
      governmental agency. Implications for leadership and group decision making are
      discussed.

PMID- 19581437
TI  - Prologue for reflections and perspectives.

PMID- 19581438
TI  - Professor Hidesaburo Hanafusa: a 50-year quest for the molecular basis of cancer.
AB  - A pioneer of oncogene research, Hidesaburo Hanafusa, Emeritus Director of the
      Osaka Bioscience Institute and Emeritus Professor of the Rockefeller University
      in New York, passed away on 15 March of this year in Japan. For his seminal works
      in cancer research during six decades (1950s until now), he received a number of
      awards including the Lasker Award, the Asahi Prize, the Ricketts Award, the
      Clowes Award, The Order of Culture (Bunka Kunsho in Japan) and the General Motors
      Sloan Award. I would like to provide a summary of his many contributions to
      research on viral and cellular oncogenes in order to appreciate the significance
      of his work on our understanding of the molecular basis of cancer and the
      implications for diagnosis and treatment.

PMID- 19581439
TI  - Yuji Tonomura: a pioneer in the field of energy transduction in muscle
      contraction.
AB  - Late Professor Yuji Tonomura has made a great contribution in the study of energy
      transduction in muscle contraction. He was the investigator who first proposed
      that a myosin-phosphate intermediate is produced subsequently to the Michaelis
      Menten complex in the pre-steady state of the myosin ATPase reaction and that it
      is a key intermediate for muscle contraction. Here, his proposed intermediate
      will be viewed from the prospective of today's understanding of actomyosin ATPase
      kinetics and in the context of myosin motor domain crystal structures.

PMID- 19581440
TI  - H2O2 activates the nuclear localization of Msn2 and Maf1 through thioredoxins in
      Saccharomyces cerevisiae.
AB  - The cellular response to hydrogen peroxide (H(2)O(2)) is characterized by a
      repression of growth-related processes and an enhanced expression of genes
      important for cell defense. In budding yeast, this response requires the
      activation of a set of transcriptional effectors. Some of them, such as the
      transcriptional activator Yap1, are specific to oxidative stress, and others,
      such as the transcriptional activators Msn2/4 and the negative regulator Maf1,
      are activated by a wide spectrum of stress conditions. How these general
      effectors are activated in response to oxidative stress remains an open question.
      In this study, we demonstrate that the two cytoplasmic thioredoxins, Trx1 and
      Trx2, are essential to trigger the nuclear accumulation of Msn2/4 and Maf1,
      specifically under H(2)O(2) treatment. Contrary to the case with many stress
      conditions previously described for yeast, the H(2)O(2)-induced nuclear
      accumulation of Msn2 and Maf1 does not correlate with the downregulation of PKA
      kinase activity. Nevertheless, we show that PP2A phosphatase activity is
      essential for driving Maf1 dephosphorylation and its subsequent nuclear
      accumulation in response to H(2)O(2) treatment. Interestingly, under this
      condition, the lack of PP2A activity has no impact on the subcellular
      localization of Msn2, demonstrating that the H(2)O(2) signaling pathways share a
      common route through the thioredoxin system and then diverge to activate Msn2 and
      Maf1, the final integrators of these pathways.

PMID- 19581441
TI  - Role of AP-1 in developmentally regulated lysosomal trafficking in Trypanosoma
      brucei.
AB  - African trypanosomes are the causative agents of human trypanosomiasis (sleeping
      sickness). The pathogenic stage of the parasite has unique adaptations to life in
      the bloodstream of the mammalian host, including upregulation of endocytic and
      lysosomal activities. We investigated stage-specific requirements for cytoplasmic
      adaptor/clathrin machinery in post-Golgi apparatus biosynthetic sorting to the
      lysosome using RNA interference silencing of the Tbmu1 subunit of adaptor complex
      1 (AP-1), in conjunction with immunolocalization, kinetic analyses of reporter
      transport, and quantitative endocytosis assays. Tbmu1 silencing was lethal in
      both stages, indicating a critical function(s) for the AP-1 machinery. Transport
      of soluble and membrane-bound secretory cargoes was Tbmu1 independent in both
      stages. In procyclic parasites, trafficking of the lysosomal membrane protein,
      p67, was disrupted, leading to cell surface mislocalization. The lysosomal
      protease trypanopain was also secreted, suggesting a transmembrane-sorting
      receptor for this soluble hydrolase. In bloodstream trypanosomes, both p67 and
      trypanopain trafficking were unaffected by Tbmu1 silencing, suggesting that AP-1
      is not necessary for biosynthetic lysosomal trafficking. Endocytosis in
      bloodstream cells was also unaffected, indicating that AP-1 does not function at
      the flagellar pocket. These results indicate that post-Golgi apparatus sorting to
      the lysosome is critically dependent on the AP-1/clathrin machinery in procyclic
      trypanosomes but that this machinery is not necessary in bloodstream parasites.
      We propose a simple model for stage-specific default secretory trafficking in
      trypanosomes that is consistent with the behavior of other soluble and
      glycosylphosphatidylinositol-anchored cargos and which is influenced by
      upregulation of endocytosis in bloodstream parasites as an adaptation to life in
      the mammalian bloodstream.

PMID- 19581442
TI  - DYF-1 Is required for assembly of the axoneme in Tetrahymena thermophila.
AB  - In most cilia, the axoneme can be subdivided into three segments: proximal (the
      transition zone), middle (with outer doublet microtubules), and distal (with
      singlet extensions of outer doublet microtubules). How the functionally distinct
      segments of the axoneme are assembled and maintained is not well understood. DYF
      1 is a highly conserved ciliary protein containing tetratricopeptide repeats. In
      Caenorhabditis elegans, DYF-1 is specifically needed for assembly of the distal
      segment (G. Ou, O. E. Blacque, J. J. Snow, M. R. Leroux, and J. M. Scholey.
      Nature. 436:583-587, 2005). We show that Tetrahymena cells lacking an ortholog of
      DYF-1, Dyf1p, can assemble only extremely short axoneme remnants that have
      structural defects of diverse natures, including the absence of central pair and
      outer doublet microtubules and incomplete or absent B tubules on the outer
      microtubules. Thus, in Tetrahymena, DYF-1 is needed for either assembly or
      stability of the entire axoneme. Our observations support the conserved function
      for DYF-1 in axoneme assembly or stability but also show that the consequences of
      loss of DYF-1 for axoneme segments are organism specific.

PMID- 19581443
TI  - Spp382p interacts with multiple yeast splicing factors, including possible
      regulators of Prp43 DExD/H-Box protein function.
AB  - Prp43p catalyzes essential steps in pre-mRNA splicing and rRNA biogenesis. In
      splicing, Spp382p stimulates the Prp43p helicase to dissociate the postcatalytic
      spliceosome and, in some way, to maintain the integrity of the spliceosome
      assembly. Here we present a dosage interference assay to identify Spp382p
      interacting factors by screening for genes that when overexpressed specifically
      inhibit the growth of a conditional lethal prp38-1 spliceosome assembly mutant in
      the spp382-1 suppressor background. Identified, among others, are genes encoding
      the established splicing factors Prp8p, Prp9p, Prp11p, Prp39p, and Yhc1p and two
      poorly characterized proteins with possible links to splicing, Sqs1p and Cwc23p.
      Sqs1p copurifies with Prp43p and is shown to bind Prp43p and Spp382p in the two
      hybrid assay. Overexpression of Sqs1p blocks pre-mRNA splicing and inhibits
      Prp43p-dependent steps in rRNA processing. Increased Prp43p levels buffer Sqs1p
      cytotoxicity, providing strong evidence that the Prp43p DExD/H-box protein is a
      target of Sqs1p. Cwc23p is the only known yeast splicing factor with a DnaJ motif
      characteristic of Hsp40-like chaperones. We show that similar to SPP382, CWC23
      activity is critical for efficient pre-mRNA splicing and intron metabolism yet,
      surprisingly, this activity does not require the canonical DnaJ/Hsp40 motif.
      These and related data establish the value of this dosage interference assay for
      finding genes that alter cellular splicing and define Sqs1p and Cwc23p as
      prospective modulators of Spp382p-stimuated Prp43p function.

PMID- 19581445
TI  - Curled encodes the Drosophila homolog of the vertebrate circadian deadenylase
      Nocturnin.
AB  - Drosophila melanogaster curled, one of the first fly mutants described by T. H.
      Morgan >90 years ago, is the founding member of a series of curled wing phenotype
      mutants widely used as markers in fruit fly genetics. The expressivity of the
      wing phenotype is environmentally modulated, suggesting that the mutation affects
      the metabolic status of cells rather than a developmental control gene. However,
      the molecular identity of any of the curled wing marker mutant genes is still
      unknown. In a screen for starvation-responsive genes, we previously identified
      the single fly homolog of the vertebrate nocturnin genes, which encode
      cytoplasmic deadenylases that act in the post-transcriptional control of genes by
      poly(A) tail removal of target mRNAs prior to their degradation. Here we show
      that curled encodes Drosophila Nocturnin and that the gene is required at pupal
      stage for proper wing morphogenesis after eclosion of the fly. Despite the
      complex ontogenetic expression pattern of the gene, curled is not expressed in
      the developing wing, and wing-specific curled knockdown mediated by RNAi does not
      result in the curled wing phenotype, indicating a tissue-nonautonomous, systemic
      mode of curled gene function. Our study not only presents an entry point into the
      functional analysis of invertebrate nocturnins but also paves the way for the
      identification of the still elusive Nocturnin target mRNAs by genetic suppressor
      screens on the curled wing phenotype.

PMID- 19581446
TI  - Candidate gene association mapping of Arabidopsis flowering time.
AB  - The pathways responsible for flowering time in Arabidopsis thaliana comprise one
      of the best characterized genetic networks in plants. We harness this extensive
      molecular genetic knowledge to identify potential flowering time quantitative
      trait genes (QTGs) through candidate gene association mapping using 51 flowering
      time loci. We genotyped common single nucleotide polymorphisms (SNPs) at these
      genes in 275 A. thaliana accessions that were also phenotyped for flowering time
      and rosette leaf number in long and short days. Using structured association
      techniques, we find that haplotype-tagging SNPs in 27 flowering time genes show
      significant associations in various trait/environment combinations. After
      correction for multiple testing, between 2 and 10 genes remain significantly
      associated with flowering time, with CO arguably possessing the most promising
      associations. We also genotyped a subset of these flowering time gene SNPs in an
      independent recombinant inbred line population derived from the intercrossing of
      19 accessions. Approximately one-third of significant polymorphisms that were
      associated with flowering time in the accessions and genotyped in the outbred
      population were replicated in both mapping populations, including SNPs at the CO,
      FLC, VIN3, PHYD, and GA1 loci, and coding region deletions at the FRI gene. We
      conservatively estimate that approximately 4-14% of known flowering time genes
      may harbor common alleles that contribute to natural variation in this life
      history trait.

PMID- 19581447
TI  - Specific genetic interactions between spindle assembly checkpoint proteins and B
      Type cyclins in Saccharomyces cerevisiae.
AB  - The B-type cyclin Clb5 is involved primarily in control of DNA replication in
      Saccharomyces cerevisiae. We conducted a synthetic genetic array (SGA) analysis,
      testing for synthetic lethality between the clb5 deletion and a selected 87
      deletions related to diverse aspects of cell cycle control based on GO
      annotations. Deletion of the spindle checkpoint genes BUB1 and BUB3 caused
      synthetic lethality with clb5. The spindle checkpoint monitors the attachment of
      spindles to the kinetochore or spindle tension during early mitosis. However,
      another spindle checkpoint gene, MAD2, could be deleted without ill effects in
      the absence of CLB5, suggesting that the bub1/3 clb5 synthetic lethality
      reflected some function other than the spindle checkpoint of Bub1 and Bub3. To
      characterize the lethality of bub3 clb5 cells, we constructed a temperature
      sensitive clb5 allele. At nonpermissive temperature, bub3 clb5-ts cells showed
      defects in spindle elongation and cytokinesis. High-copy plasmid suppression of
      bub3 clb5 lethality identified the C-terminal fragment of BIR1, the yeast homolog
      of survivin; cytologically, the BIR1 fragment rescued the growth and cytokinesis
      defects. Bir1 interacts with IplI (Aurora B homolog), and the addition of bub3
      clb5-ts significantly enhanced the lethality of the temperature-sensitive ipl1
      321. Overall, we conclude that the synthetic lethality between clb5 and bub1 or
      bub3 is likely related to functions of Bub1/3 unrelated to their spindle
      checkpoint function. We tested requirements for other B-type cyclins in the
      absence of spindle checkpoint components. In the absence of the related CLB3 and
      CLB4 cyclins, the spindle integrity checkpoint becomes essential, since bub3 or
      mad2 deletion is lethal in a clb3 clb4 background. clb3 clb4 mad2 cells
      accumulated with unseparated spindle pole bodies. Thus, different B-type cyclins
      are required for distinct aspects of spindle morphogenesis and function, as
      revealed by differential genetic interactions with spindle checkpoint components.

PMID- 19581450
TI  - Is there variation in crossover interference levels among chromosomes from human
      males?
AB  - We demonstrate that recent data from human males are consistent with constant
      interference levels among chromosomes under the two-pathway model, whereas
      inappropriately fitting shape parameters of Gamma distributions to
      immunofluorescent interfoci distances observed on finite chromosomes generates
      false interpretations of higher levels of interference on shorter chromosomes. We
      provide appropriate statistical methodology.

PMID- 19581448
TI  - Polymorphisms in multiple genes contribute to the spontaneous mitochondrial
      genome instability of Saccharomyces cerevisiae S288C strains.
AB  - The mitochondrial genome (mtDNA) is required for normal cellular function;
      inherited and somatic mutations in mtDNA lead to a variety of diseases.
      Saccharomyces cerevisiae has served as a model to study mtDNA integrity, in part
      because it can survive without mtDNA. A measure of defective mtDNA in S.
      cerevisiae is the formation of petite colonies. The frequency at which
      spontaneous petite colonies arise varies by approximately 100-fold between
      laboratory and natural isolate strains. To determine the genetic basis of this
      difference, we applied quantitative trait locus (QTL) mapping to two strains at
      the opposite extremes of the phenotypic spectrum: the widely studied laboratory
      strain S288C and the vineyard isolate RM11-1a. Four main genetic determinants
      explained the phenotypic difference. Alleles of SAL1, CAT5, and MIP1 contributed
      to the high petite frequency of S288C and its derivatives by increasing the
      formation of petite colonies. By contrast, the S288C allele of MKT1 reduced the
      formation of petite colonies and compromised the growth of petite cells. The
      former three alleles were found in the EM93 strain, the founder that contributed
      approximately 88% of the S288C genome. Nearly all of the phenotypic difference
      between S288C and RM11-1a was reconstituted by introducing the common alleles of
      these four genes into the S288C background. In addition to the nuclear gene
      contribution, the source of the mtDNA influenced its stability. These results
      demonstrate that a few rare genetic variants with individually small effects can
      have a profound phenotypic effect in combination. Moreover, the polymorphisms
      identified in this study open new lines of investigation into mtDNA maintenance.

PMID- 19581444
TI  - The population genomics of trans-specific inversion polymorphisms in Anopheles
      gambiae.
AB  - In the malaria mosquito Anopheles gambiae polymorphic chromosomal inversions may
      play an important role in adaptation to environmental variation. Recently, we
      used microarray-based divergence mapping combined with targeted resequencing to
      map nucleotide differentiation between alternative arrangements of the 2La
      inversion. Here, we applied the same technique to four different polymorphic
      inversions on the 2R chromosome of An. gambiae. Surprisingly, divergence was much
      lower between alternative arrangements for all 2R inversions when compared to the
      2La inversion. For one of the rearrangements, 2Ru, we successfully mapped a very
      small region (approximately 100 kb) of elevated divergence. For the other three
      rearrangements, we did not identify any regions of significantly high divergence,
      despite ample independent evidence from natural populations of geographic clines
      and seasonal cycling, and stable heterotic polymorphisms in laboratory
      populations. If these inversions are the targets of selection as hypothesized, we
      suggest that divergence between rearrangements may have escaped detection due to
      retained ancestral polymorphism in the case of the youngest 2R rearrangements and
      to extensive gene flux in the older 2R inversion systems that segregate in both
      An. gambiae and its sibling species An. arabiensis.

PMID- 19581449
TI  - KlAft, the Kluyveromyces lactis ortholog of Aft1 and Aft2, mediates activation of
      iron-responsive transcription through the PuCACCC Aft-type sequence.
AB  - Iron homeostasis in fungi is regulated at the transcriptional level by two
      different mechanisms. It is mediated by a conserved GATA-type repressor in most
      fungi except in the yeast Saccharomyces cerevisiae, where it is controlled by the
      transcription activators Aft1 and Aft2. These activators are encoded by the
      paralogous genes AFT1 and AFT2, which result from the whole-genome duplication.
      Here, we explore regulation of iron homeostasis in the yeast Kluyveromyces lactis
      that diverged from S. cerevisiae before this event. We identify an ortholog of
      AFT1/AFT2, designated KlAFT, whose deletion leads to the inability to grow under
      iron limitation. We show with quantitative real-time PCR analysis that KlAft
      activates the transcription of all homologs of the Aft1-target genes involved in
      the iron transport at the cell surface in response to iron limitation. However,
      homologs of Aft2-specific target genes encoding intracellular iron transporters
      are regulated neither by KlAft nor by iron. Both bioinformatic and DNA binding
      and transcription analyses demonstrate that KlAft activates iron-responsive gene
      expression through the PuCACCC Aft-type sequence. Thus, K. lactis is the first
      documented species with a positive iron-transcriptional control mediated by only
      one copy of the Aft-type regulator. This indicates that this function was
      acquired before the whole-genome duplication and was then diversified into two
      regulators in S. cerevisiae.

PMID- 19581452
TI  - Ancestral population genomics: the coalescent hidden Markov model approach.
AB  - With incomplete lineage sorting (ILS), the genealogy of closely related species
      differs along their genomes. The amount of ILS depends on population parameters
      such as the ancestral effective population sizes and the recombination rate, but
      also on the number of generations between speciation events. We use a hidden
      Markov model parameterized according to coalescent theory to infer the genealogy
      along a four-species genome alignment of closely related species and estimate
      population parameters. We analyze a basic, panmictic demographic model and study
      its properties using an extensive set of coalescent simulations. We assess the
      effect of the model assumptions and demonstrate that the Markov property provides
      a good approximation to the ancestral recombination graph. Using a too restricted
      set of possible genealogies, necessary to reduce the computational load, can bias
      parameter estimates. We propose a simple correction for this bias and suggest
      directions for future extensions of the model. We show that the patterns of ILS
      along a sequence alignment can be recovered efficiently together with the
      ancestral recombination rate. Finally, we introduce an extension of the basic
      model that allows for mutation rate heterogeneity and reanalyze human-chimpanzee
      gorilla-orangutan alignments, using the new models. We expect that this framework
      will prove useful for population genomics and provide exciting insights into
      genome evolution.

PMID- 19581453
TI  - Inhibition of intracellular growth of Salmonella enterica serovar Typhimurium in
      tissue culture by antisense peptide-phosphorodiamidate morpholino oligomer.
AB  - Two types of phosphorodiamidate morpholino oligomers (PMOs) were tested for
      inhibition of growth of Salmonella enterica serovar Typhimurium. Both PMOs have
      the same 11-base sequence that is antisense to the region near the start codon of
      acpP, which is essential for lipid biosynthesis and viability. To the 3' end of
      each is attached the membrane-penetrating peptide (RXR)4XB (R, X, and B indicate
      arginine, 6-aminohexanoic acid, and beta-alanine, respectively). One peptide-PMO
      (AcpP PPMO) has no charge on the PMO moiety. The second PPMO has three cations
      (piperazine) attached to the phosphorodiamidate linkages (3+Pip-AcpP PPMO). A
      scrambled-sequence PPMO (Scr PPMO) was synthesized for each type of PMO. The MICs
      of AcpP PPMO, 3+Pip-AcpP PPMO, and either one of the Scr PPMOs were 1.25 microM
      (7 microg/ml), 0.156 microM (0.94 microg/ml), and >160 microM (>900 microg/ml),
      respectively. 3+Pip-AcpP PPMO at 1.25 or 2.5 microM significantly reduced the
      growth rates of pure cultures, whereas AcpP PPMO or either Scr PPMO had no
      effect. However, the viable cell count was significantly reduced at either
      concentration of 3+Pip-AcpP PPMO or AcpP PPMO, but not with either Scr PPMO. In
      other experiments, macrophages were infected intracellularly with S. enterica and
      treated with 3 microM 3+Pip-AcpP PPMO. Intracellular bacteria were reduced >99%
      with 3+Pip-AcpP PPMO, whereas intracellular bacteria increased 3 orders of
      magnitude in untreated or Scr PPMO-treated cultures. We conclude that either AcpP
      PPMO or 3+Pip-AcpP PPMO inhibited growth of S. enterica in pure culture and that
      3+Pip-AcpP PPMO reduced intracellular viability of S. enterica in macrophages.

PMID- 19581454
TI  - Combination chemotherapy against Clonorchis sinensis: experiments with
      artemether, artesunate, OZ78, praziquantel, and tribendimidine in a rat model.
AB  - Caused by the Chinese liver fluke Clonorchis sinensis, clonorchiasis is of
      growing public health importance. Treatment and control of the disease rely on a
      single drug, praziquantel, and little information regarding combination
      chemotherapy is available. Here, we evaluated the in vivo efficacy of
      praziquantel combined with artemether, artesunate, OZ78, and tribendimidine, as
      well as an artesunate-tribendimidine combination against C. sinensis, in a rat
      model. Data from previous experiments were included, and negative binomial
      regression analyses were carried out to determine dose-response relationships and
      to study the effect of drug combination. All drugs given in monotherapy were
      efficacious in killing the worms; doses of 16 and 70 mg/kg of body weight of
      artesunate, for example, reduced worm burden by 50% and 95%, respectively.
      Artemether and OZ78 (12.5 to 50 mg/kg) showed dose-dependent killing of worms but
      no significant drug interactions when given with 150 mg/kg praziquantel,
      suggesting independent additive effects. In contrast, artesunate and
      tribendimidine (12.5 to 50 mg/kg) showed synergistic interactions with 150 mg/kg
      praziquantel. When low doses of 3.1 and 6.25 mg/kg OZ78 and artemether,
      respectively, were combined with praziquantel (150 mg/kg) an increased worm
      survival, above the level observed with praziquantel monotherapy, was noted. A
      similar antagonism was seen when praziquantel (75 mg/kg) was combined with
      several of the companion drugs at various doses. In conclusion, in vivo efficacy
      of praziquantel, the artemisinins, OZ78, and tribendimidine against C. sinensis
      is confirmed, and combination chemotherapy with praziquantel produces synergistic
      and antagonistic effects depending on the doses administered. Further preclinical
      investigations are warranted.

PMID- 19581455
TI  - Intravenous doripenem at 500 milligrams versus levofloxacin at 250 milligrams,
      with an option to switch to oral therapy, for treatment of complicated lower
      urinary tract infection and pyelonephritis.
AB  - The prospective, multicenter, double-blind study presented in this report
      evaluated whether or not intravenous (IV) administration of doripenem, a
      carbapenem with bactericidal activity against gram-negative and gram-positive
      uropathogens, is inferior to IV administration of levofloxacin in the treatment
      of complicated urinary tract infection (cUTI). Patients (n = 753) with
      complicated lower UTI or pyelonephritis were randomly assigned to receive IV
      doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients
      in both treatment arms were eligible to switch to oral levofloxacin after 3 days
      of IV therapy to complete a 10-day treatment course if they demonstrated
      significant clinical and microbiological improvements. The microbiological cure
      rate (primary end point) was determined at the test-of-cure (TOC) visit occurring
      5 to 11 days after the last dose of antibiotic. For the microbiologically
      evaluable patients (n = 545), the microbiological cure rates were 82.1% and 83.4%
      for doripenem and levofloxacin, respectively (95% confidence interval [CI] for
      the difference, -8.0 to 5.5%); in the microbiological modified intent-to-treat
      cohort (n = 648), the cure rates were 79.2% and 78.2%, respectively. Clinical
      cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the
      levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate
      minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were
      generally well tolerated. Doripenem was found not to be inferior to levofloxacin
      in terms of therapeutics and is now approved for use in the United States and
      Europe for the treatment of adults with cUTI, including pyelonephritis. As
      fluoroquinolone resistance increases, doripenem may become a more important
      option for successful treatment of cUTIs, including treatment of pyelonephritis.

PMID- 19581456
TI  - Evaluation of analogs of reutericyclin as prospective candidates for treatment of
      staphylococcal skin infections.
AB  - The potential for reutericyclin derivatives to be used as topical antibiotics to
      treat staphylococcal skin infections was investigated. All reutericyclins
      inhibited the growth of clinical isolates of drug-resistant Staphylococcus
      aureus. Unlike the standard topical agent mupirocin, most reutericyclin
      derivatives eradicated staphylococcal biofilms. Moreover, two compounds
      formulated in hydrophilic petrolatum (10%, wt/wt) were efficacious in treating S.
      aureus superficial skin infections in mice. These data exemplify the prospect of
      developing reutericyclins as new topical antibiotics.

PMID- 19581457
TI  - In vitro activities of telavancin and six comparator agents against anaerobic
      bacterial isolates.
AB  - The antimicrobial activities of telavancin and six comparators were evaluated
      against 460 isolates of anaerobic bacteria. Telavancin demonstrated excellent
      activity against gram-positive anaerobes (MIC90, 2 microg/ml) and was the most
      potent agent tested against Clostridium difficile (MIC90, 0.25 microg/ml). As
      expected, gram-negative isolates were not inhibited by telavancin.

PMID- 19581451
TI  - Splicing variation at a FLOWERING LOCUS C homeolog is associated with flowering
      time variation in the tetraploid Capsella bursa-pastoris.
AB  - The long-term fates of duplicate genes are well studied both empirically and
      theoretically, but how the short-term evolution of duplicate genes contributes to
      phenotypic variation is less well known. Here, we have studied the genetic basis
      of flowering time variation in the disomic tetraploid Capsella bursa-pastoris. We
      sequenced four duplicate candidate genes for flowering time and 10 background
      loci in samples from western Eurasia and China. Using a mixed-model approach that
      accounts for population structure, we found that polymorphisms at one homeolog of
      two candidate genes, FLOWERING LOCUS C (FLC) and CRYPTOCHROME1 (CRY1), were
      associated with natural flowering time variation. No potentially causative
      polymorphisms were found in the coding region of CRY1; however, at FLC two splice
      site polymorphisms were associated with early flowering. Accessions harboring
      nonconsensus splice sites expressed an alternatively spliced transcript or did
      not express this FLC homeolog. Our results are consistent with the function of
      FLC as a major repressor of flowering in Arabidopsis thaliana and imply that
      nonfunctionalization of duplicate genes could provide an important source of
      phenotypic variation.

PMID- 19581458
TI  - CraA, a major facilitator superfamily efflux pump associated with chloramphenicol
      resistance in Acinetobacter baumannii.
AB  - Acinetobacter baumannii has been increasingly associated with hospital-acquired
      infections, and the presence of multidrug resistance strains is of great concern
      to clinicians. A. baumannii is thought to possess a great deal of intrinsic
      resistance to several antimicrobial agents, including chloramphenicol, although
      the mechanisms involved in such resistance are not well understood. In this work,
      we have identified a major facilitator superfamily efflux pump present in most A.
      baumannii strains, displaying strong substrate specificity toward
      chloramphenicol.

PMID- 19581459
TI  - Emerging Klebsiella pneumoniae isolates coproducing KPC-2 and VIM-1
      carbapenemases.

PMID- 19581460
TI  - Lipid segregation explains selective toxicity of a series of fragments derived
      from the human cathelicidin LL-37.
AB  - The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial
      activity against both gram-positive and gram-negative bacteria. We studied the
      ability of several fragments of LL-37, exhibiting different antimicrobial
      activities, to interact with membranes whose compositions mimic the cytoplasmic
      membranes of gram-positive or of gram-negative bacteria. These fragments are as
      follows: KR-12, the smallest active segment of LL-37, with the sequence
      KRIVQRIKDFLR, which exhibits antimicrobial activity only against gram-negative
      bacteria; a slightly smaller peptide, RI-10, missing the two cationic residues at
      the N and C termini of KR-12, which has been shown not to have any antimicrobial
      activity; a longer peptide, GF-17, which shows antimicrobial activity against
      gram-positive as well as gram-negative bacteria; and GF-17D3, with 3 D-amino-acid
      residues, which is also selective only for gram-negative bacteria. Those
      fragments with the capacity to cluster anionic lipids away from zwitterionic
      lipids in a membrane exhibit selective toxicity toward bacteria containing
      zwitterionic as well as anionic lipids in their cytoplasmic membranes but not
      toward bacteria with only anionic lipids. This finding allows for the prediction
      of the bacterial-species selectivity of certain agents and paves the way for
      designing new antimicrobials targeted specifically toward gram-negative bacteria.

PMID- 19581461
TI  - Didanosine population pharmacokinetics in West African human immunodeficiency
      virus-infected children administered once-daily tablets in relation to efficacy
      after one year of treatment.
AB  - Our objective was to study didanosine pharmacokinetics in children after the
      administration of tablets, the only formulation available in Burkina Faso for
      which data are missing, and to establish relationships between doses, plasma drug
      concentrations, and treatment effects (efficacy/toxicity). Didanosine
      concentrations were measured for 40 children after 2 weeks and for 9 children
      after 2 to 5 months of treatment with a didanosine-lamivudine-efavirenz
      combination. A population pharmacokinetic model was developed with NONMEM. The
      link between the maximal concentration of the drug in plasma (Cmax), the area
      under the concentration-time curve (AUC), and the decrease in human
      immunodeficiency virus (HIV) type 1 RNA levels after 12 months of treatment was
      evaluated. The threshold AUC that improved efficacy was determined by the use of
      a Wilcoxon test for HIV RNA, and an optimized dosing schedule was simulated.
      Didanosine pharmacokinetics was best described by a one-compartment model with
      first-order absorption and elimination. The apparent clearance and volume of
      distribution were higher for tablets, probably due to a lower bioavailability
      with tablets than with pediatric powder. The decrease in the viral load after 12
      months of treatment was significantly correlated with the didanosine AUC and Cmax
      (P < or = 0.02) during the first weeks of treatment. An AUC of >0.60 mg/liter x h
      was significantly linked to a greater decrease in the viral load (a decrease of 3
      log10 versus 2.4 log10 copies/ml; P = 0.03) than that with a lower AUC. A
      didanosine dose of 360 mg/m2 administered as tablets should be a more appropriate
      dose than 240 mg/m2 to improve efficacy for these children. However, data on
      adverse events with this dosage are missing.

PMID- 19581462
TI  - Contribution of dfrA and inhA mutations to the detection of isoniazid-resistant
      Mycobacterium tuberculosis isolates.
AB  - Screening of 127 isoniazid (INH)-resistant Mycobacterium tuberculosis isolates
      from Singapore for mutations within the dfrA and inhA genes revealed mutations in
      0 and 5 (3.9%) isolates respectively, implying that mutations in dfrA do not
      contribute to the detection of INH-resistant M. tuberculosis and that mutations
      within inhA are rare. Thirty-seven (29%) of the 127 isolates had no mutations in
      any of the genes implicated in INH resistance (katG, kasA, and ndh; inhA and ahpC
      promoters), suggesting that there are new INH targets yet to be discovered.

PMID- 19581463
TI  - Meropenem pharmacokinetics in the newborn.
AB  - We studied meropenem in 23 pre-term (gestational age, 29 to 36 weeks) and 15 full
      term (gestational age, 37 to 42 weeks) neonates. Meropenem doses of 10, 20, and
      40 mg/kg were administered as single doses (30-min intravenous infusion) on a
      random basis. Blood was obtained for determining the meropenem concentration nine
      times. Each child required other antimicrobials for proven/suspected bacterial
      infections. Samples were assayed by high-performance liquid chromatography
      analysis. Population pharmacokinetic parameter values were obtained by employing
      the BigNPAG program. Model building was performed by the likelihood ratio test.
      The final model included estimated creatinine clearance (CLcr) (Schwartz formula)
      and weight (Wt) in the calculation of clearance (meropenem clearance = 0.00112 x
      CLcr + 0.0925 x Wt + 0.156 liter/hr). The overall fit of the model to the data
      was good (observed = 1.037 x predicted - 0.096; r2 = 0.977). Given the
      distributions of estimated creatinine clearance and weight between pre-term and
      full-term neonates, meropenem clearance was substantially higher in the full-term
      group. A Monte Carlo simulation was performed using the creatinine clearance and
      weight distributions for pre-term and full-term populations separately, examining
      20- and 40-mg/kg doses, 8- and 12-h dosing intervals, and 0.5-h and 4-h infusion
      times. The 8-h interval produced robust target attainments (both populations). If
      more resistant organisms were to be treated (MIC of 4 to 8 mg/liter), the 40
      mg/kg dose and a prolonged infusion was favored. Treating clinicians need to
      balance dose choices for optimizing target attainment against potential toxicity.
      These findings require validation in clinical circumstances.

PMID- 19581464
TI  - Experimental chemotherapy against Trypanosoma cruzi infection using ruthenium
      nitric oxide donors.
AB  - The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L]n+, where the ligand
      (L) is N-heterocyclic H2O, SO(3)(2-), or triethyl phosphite, are able to lyse
      Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory
      concentrations against bloodstream trypomastigotes (IC50try) and cytotoxicity
      data on mammalian V-79 cells (IC50V79), the in vitro therapeutic indices (TIs)
      (IC50V79/IC50try) for these compounds were calculated. Compounds that exhibited
      an in vitro TI of > or = 10 and trypanocidal activity against both epimastigotes
      and trypomastigotes with an IC50(try/epi) of < or = 100 microM were assayed in a
      mouse model for acute Chagas' disease, using two different routes
      (intraperitoneal and oral) for drug administration. A dose-effect relationship
      was observed, and from that, the ideal dose of 400 nmol/kg of body weight for
      both trans-[Ru(NO)(NH3)4isn](BF4)3 (isn, isonicotinamide) and trans
      [Ru(NO)(NH3)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50)
      of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal
      doses (LD50) for both compounds are higher than 125 micromol/kg, the in vivo TIs
      (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(NH3)4isn](BF4)3 and 658
      for trans-[Ru(NO)(NH3)4imN](BF4)3. Although these compounds exhibit a marked
      trypanocidal activity and are able to react with cysteine, they exhibit very low
      activity in T. cruzi-glycosomal glyceraldehyde-3-phosphate dehydrogenase tests,
      suggesting that this enzyme is not their target. The trans
      [Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 compounds are able to
      eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure
      the survival of all infected mice, thus opening a novel set of therapies to try
      against trypanosomatids.

PMID- 19581465
TI  - Role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium
      chelonae to aldehyde-based disinfectants and drugs.
AB  - Nosocomial outbreaks attributable to glutaraldehyde-resistant, rapidly growing
      mycobacteria are increasing. Here, evidence is provided that defects in porin
      expression dramatically increase the resistance of Mycobacterium smegmatis and
      Mycobacterium chelonae to glutaraldehyde and another aldehyde disinfectant, ortho
      phthalaldehyde. Since defects in porin activity also dramatically increased the
      resistance of M. chelonae to drugs, there is thus some concern that the
      widespread use of glutaraldehyde and ortho-phthalaldehyde in clinical settings
      may select for drug-resistant bacteria.

PMID- 19581466
TI  - Impact of therapeutic treatment with beta-lactam on transfer of the bla(CTX-M-9)
      resistance gene from Salmonella enterica serovar Virchow to Escherichia coli in
      gnotobiotic rats.
AB  - The conjugative transfer of the plasmid carrying the bla(CTX-M-9) gene from
      Salmonella enterica serovar Virchow isolated from a chicken farm to a recipient
      Escherichia coli strain was evaluated in vitro and in axenic rats inoculated with
      both strains, with or without selective pressure due to therapeutic doses of
      cefixime. The transfer of the bla(CTX-M-9) gene of S. enterica serovar Virchow to
      E. coli was confirmed in vitro, at a low frequency of 5.9 x 10(-8)
      transconjugants/donors. This transfer rate was higher in gnotobiotic rats and
      reached approximately 10(-5) transconjugants/donors without selective pressure.
      This frequency was not affected by the addition of therapeutic doses of cefixime.
      Thus, estimates of in vitro transfer underestimated potential transfer in the
      digestive tract, and therapeutic doses of cefixime did not increase the selection
      for transconjugants.

PMID- 19581467
TI  - Genetic analysis of a novel Xylella fastidiosa subspecies found in the
      southwestern United States.
AB  - Xylella fastidiosa, the causal agent of several scorch diseases, is associated
      with leaf scorch symptoms in Chitalpa tashkentensis, a common ornamental
      landscape plant used throughout the southwestern United States. For a number of
      years, many chitalpa trees in southern New Mexico and Arizona exhibited leaf
      scorch symptoms, and the results from a regional survey show that chitalpa trees
      from New Mexico, Arizona, and California are frequently infected with X.
      fastidiosa. Phylogenetic analysis of multiple loci was used to compare the X.
      fastidiosa infecting chitalpa strains from New Mexico, Arizona, and trees
      imported into New Mexico nurseries with previously reported X. fastidiosa
      strains. Loci analyzed included the 16S ribosome, 16S-23S ribosomal intergenic
      spacer region, gyrase-B, simple sequence repeat sequences, X. fastidiosa-specific
      sequences, and the virulence-associated protein (VapD). This analysis indicates
      that the X. fastidiosa isolates associated with infected chitalpa trees in the
      Southwest are a highly related group that is distinct from the four previously
      defined taxons X. fastidiosa subsp. fastidiosa (piercei), X. fastidiosa subsp.
      multiplex, X. fastidiosa subsp. sandyi, and X. fastidiosa subsp. pauca.
      Therefore, the classification proposed for this new subspecies is X. fastidiosa
      subsp. tashke.

PMID- 19581468
TI  - Bacterial chemotaxis to atrazine and related s-triazines.
AB  - Pseudomonas sp. strain ADP utilizes the human-made s-triazine herbicide atrazine
      as the sole nitrogen source. The results reported here demonstrate that atrazine
      and the atrazine degradation intermediates N-isopropylammelide and cyanuric acid
      are chemoattractants for strain ADP. In addition, the nonmetabolized s-triazine
      ametryn was also an attractant. The chemotactic response to these s-triazines was
      not specifically induced during growth with atrazine, and atrazine metabolism was
      not required for the chemotactic response. A cured variant of strain ADP (ADP M13
      2) was attracted to s-triazines, indicating that the atrazine catabolic plasmid
      pADP-1 is not necessary for the chemotactic response and that atrazine
      degradation and chemotaxis are not genetically linked. These results indicate
      that atrazine and related s-triazines are detected by one or more chromosomally
      encoded chemoreceptors in Pseudomonas sp. strain ADP. We demonstrated that
      Escherichia coli is attracted to the s-triazine compounds N-isopropylammelide and
      cyanuric acid, and an E. coli mutant lacking Tap (the pyrimidine chemoreceptor)
      was unable to respond to s-triazines. These data indicate that pyrimidines and
      triazines are detected by the same chemoreceptor (Tap) in E. coli. We showed that
      Pseudomonas sp. strain ADP is attracted to pyrimidines, which are the naturally
      occurring structures closest to triazines, and propose that chemotaxis toward s
      triazines may be due to fortuitous recognition by a pyrimidine chemoreceptor in
      Pseudomonas sp. strain ADP. In competition assays, the presence of atrazine
      inhibited chemotaxis of Pseudomonas sp. strain ADP to cytosine, and cytosine
      inhibited chemotaxis to atrazine, suggesting that pyrimidines and s-triazines are
      detected by the same chemoreceptor.

PMID- 19581470
TI  - Characterization of mundticin L, a class IIa anti-Listeria bacteriocin from
      Enterococcus mundtii CUGF08.
AB  - Enterococcus mundtii CUGF08, a lactic acid bacterium isolated from alfalfa
      sprouts, was found to produce mundticin L, a new class IIa bacteriocin that has a
      high level of inhibitory activity against the genus Listeria. The plasmid
      associated operons containing genes for the mundticin L precursor, the ATP
      binding cassette (ABC) transporter, and immunity were cloned and sequenced. The
      fifth residue of the conservative consensus sequence YGNGX in the mature
      bacteriocin is leucine instead of valine in the sequences of the homologous
      molecules mundticin KS (ATO6) and enterocin CRL35. The primary structures of the
      ABC transporter and the immunity protein are homologous but unique.

PMID- 19581471
TI  - Carbohydrate metabolism differences between subgroup A1 and B2 strains of
      Bacillus anthracis as assessed by comparative genomics and functional genetics.
AB  - In France, Bacillus anthracis subgroup B2 strains do not metabolize starch or
      glycogen but can use gluconate, whereas subgroup A1 strains show the inverse
      pattern. Functional genetic analysis revealed that mutations in the amyS and gntK
      genes encoding an alpha-amylase and a gluconate kinase, respectively, were
      responsible for these phenotypes.

PMID- 19581469
TI  - Metabolism and cometabolism of cyclic ethers by a filamentous fungus, a Graphium
      sp.
AB  - The filamentous fungus Graphium sp. (ATCC 58400) grows on gaseous n-alkanes and
      diethyl ether. n-Alkane-grown mycelia of this strain also cometabolically oxidize
      the gasoline oxygenate methyl tert-butyl ether (MTBE). In this study, we
      characterized the ability of this fungus to metabolize and cometabolize a range
      of cyclic ethers, including tetrahydrofuran (THF) and 1,4-dioxane (14D). This
      strain grew on THF and other cyclic ethers, including tetrahydropyran and
      hexamethylene oxide. However, more vigorous growth was consistently observed on
      the lactones and terminal diols potentially derived from these ethers. Unlike the
      case in all previous studies of microbial THF oxidation, a metabolite, gamma
      butyrolactone, was observed during growth of this fungus on THF. Growth on THF
      was inhibited by the same n-alkenes and n-alkynes that inhibit growth of this
      fungus on n-alkanes, while growth on gamma-butyrolactone or succinate was
      unaffected by these inhibitors. Propane and THF also behaved as mutually
      competitive substrates, and propane-grown mycelia immediately oxidized THF,
      without a lag phase. Mycelia grown on propane or THF exhibited comparable high
      levels of hemiacetal-oxidizing activity that generated methyl formate from
      mixtures of formaldehyde and methanol. Collectively, these observations suggest
      that THF and n-alkanes may initially be oxidized by the same monooxygenase and
      that further transformation of THF-derived metabolites involves the activity of
      one or more alcohol dehydrogenases. Both propane- and THF-grown mycelia also
      slowly cometabolically oxidized 14D, although unlike THF oxidation, this reaction
      was not sustainable. Specific rates of THF, 14D, and MTBE degradation were very
      similar in THF- and propane-grown mycelia.

PMID- 19581472
TI  - pulsed-field gel electrophoresis profile changes resulting from spontaneous
      chromosomal deletions in enterohemorrhagic Escherichia coli O157:H7 during
      passage in cattle.
AB  - A total of 905 enterohemorrhagic Escherichia coli (EHEC) O157:H7 isolates that
      were recovered from experimentally infected cattle, in addition to the inoculated
      strain, were analyzed by pulsed-field gel electrophoresis (PFGE). Twelve PFGE
      profiles other than that of the inoculated strain were observed. We successfully
      identified five distinct chromosomal deletions that affected the PFGE profiles
      using whole-genome PCR scanning and DNA sequencing analysis. The changes in PFGE
      profiles of EHEC O157:H7 isolates after passage through the intestinal tract of
      cattle were partially generated by deletion of chromosomal regions.

PMID- 19581473
TI  - Tolerance of the Ralstonia eutropha class I polyhydroxyalkanoate synthase for
      translational fusions to its C terminus reveals a new mode of functional display.
AB  - Here, the class I polyhydroxyalkanoate synthase (PhaC) from Ralstonia eutropha
      was investigated regarding the functionality of its conserved C-terminal region
      and its ability to tolerate translational fusions to its C terminus. MalE, the
      maltose binding protein, and green fluorescent protein (GFP) were considered
      reporter proteins to be translationally fused to the C terminus. Interestingly,
      PhaC remained active only when a linker was inserted between PhaC and MalE,
      whereas MalE was not functional. However, the extension of the PhaC N terminus by
      458 amino acid residues was required to achieve a functionality of MalE. These
      data suggested a positive interaction of the extended N terminus with the C
      terminus. To assess whether a linker and/or N-terminal extension is generally
      required for a functional C-terminal fusion, GFP was fused to the C terminus of
      PhaC. Both fusion partners were active without the requirement of a linker and/or
      N-terminal extension. A further reporter protein, the immunoglobulin G binding ZZ
      domain of protein A, was translationally fused to the N terminus of the fusion
      protein PhaC-GFP and resulted in a tripartite fusion protein mediating the
      production of polyester granules displaying two functional protein domains.

PMID- 19581475
TI  - Identification of amino acid residues responsible for the enantioselectivity and
      amide formation capacity of the Arylacetonitrilase from Pseudomonas fluorescens
      EBC191.
AB  - The nitrilase from Pseudomonas fluorescens EBC191 converted (R,S)-mandelonitrile
      with a low enantioselectivity to (R)-mandelic acid and (S)-mandeloamide in a
      ratio of about 4:1. In contrast, the same substrate was hydrolyzed by the
      homologous nitrilase from Alcaligenes faecalis ATCC 8750 almost exclusively to
      (R)-mandelic acid. A chimeric enzyme between both nitrilases was constructed,
      which represented in total 16 amino acid exchanges in the central part of the
      nitrilase from P. fluorescens EBC191. The chimeric enzyme clearly resembled the
      nitrilase from A. faecalis ATCC 8750 in its turnover characteristics for (R,S)
      mandelonitrile and (R,S)-2-phenylpropionitrile (2-PPN) and demonstrated an even
      higher enantioselectivity for the formation of (R)-mandelic acid than the
      nitrilase from A. faecalis. An alanine residue (Ala165) in direct proximity to
      the catalytically active cysteine residue was replaced in the nitrilase from P.
      fluorescens by a tryptophan residue (as found in the nitrilase from A. faecalis
      ATCC 8750 and most other bacterial nitrilases) and several other amino acid
      residues. Those enzyme variants that possessed a larger substituent in position
      165 (tryptophan, phenylalanine, tyrosine, or histidine) converted racemic
      mandelonitrile and 2-PPN to increased amounts of the R enantiomers of the
      corresponding acids. The enzyme variant Ala165His showed a significantly
      increased relative activity for mandelonitrile (compared to 2-PPN), and the
      opposite was found for the enzyme variants carrying aromatic residues in the
      relevant position. The mutant forms carrying an aromatic substituent in position
      165 generally formed significantly reduced amounts of mandeloamide from
      mandelonitrile. The important effect of the corresponding amino acid residue on
      the reaction specificity and enantiospecificity of arylacetonitrilases was
      confirmed by the construction of a Trp164Ala variant of the nitrilase from A.
      faecalis ATCC 8750. This point mutation converted the highly R-specific nitrilase
      into an enzyme that converted (R,S)-mandelonitrile preferentially to (S)
      mandeloamide.

PMID- 19581476
TI  - Prevalence of antibiotic resistance in drinking water treatment and distribution
      systems.
AB  - The occurrence and spread of antibiotic-resistant bacteria (ARB) are pressing
      public health problems worldwide, and aquatic ecosystems are a recognized
      reservoir for ARB. We used culture-dependent methods and quantitative molecular
      techniques to detect and quantify ARB and antibiotic resistance genes (ARGs) in
      source waters, drinking water treatment plants, and tap water from several cities
      in Michigan and Ohio. We found ARGs and heterotrophic ARB in all finished water
      and tap water tested, although the amounts were small. The quantities of most
      ARGs were greater in tap water than in finished water and source water. In
      general, the levels of bacteria were higher in source water than in tap water,
      and the levels of ARB were higher in tap water than in finished water, indicating
      that there was regrowth of bacteria in drinking water distribution systems.
      Elevated resistance to some antibiotics was observed during water treatment and
      in tap water. Water treatment might increase the antibiotic resistance of
      surviving bacteria, and water distribution systems may serve as an important
      reservoir for the spread of antibiotic resistance to opportunistic pathogens.

PMID- 19581477
TI  - Some Listeria monocytogenes outbreak strains demonstrate significantly reduced
      invasion, inlA transcript levels, and swarming motility in vitro.
AB  - Listeria monocytogenes can cause a severe invasive food-borne disease known as
      listeriosis, and large outbreaks of this disease occur occasionally. Based on
      molecular-subtype data, epidemic clone (EC) strains have been defined, including
      ECI and ECIa, which have caused listeriosis outbreaks on different continents.
      While a number of molecular-subtyping studies of outbreak strains have been
      reported, few comprehensive data sets of virulence-associated characteristics of
      these strains are available. We assembled a set of human clinical isolates from
      15 outbreaks that occurred worldwide between 1975 and 2002. Initial
      characterization of these strains showed significant variation in the ability to
      invade human Caco-2 intestinal epithelial cells and HepG2 hepatic cells; four
      strains showed consistently reduced invasion in both cell lines. DNA sequencing
      of inlA, which encodes a protein required for efficient Caco-2 and HepG2
      invasion, showed that none of the invasion-attenuated strains contained known
      virulence-attenuating mutations in inlA. Phylogenetic analyses of inlA sequences
      revealed a well-supported clade containing a fully invasive ECI strain and three
      invasion-attenuated ECI strains, along with a fully invasive ECIa strain and an
      invasion-attenuated ECIa strain. Of the four invasion-attenuated strains, one
      strain showed both reduced inlA transcript levels and impaired swarming, one
      strain showed reduced inlA transcript levels, and two strains showed reduced
      swarming. Overall, our data show that (i) L. monocytogenes strains from outbreaks
      vary significantly in invasion efficiency and (ii) different mechanisms may
      contribute to reduced invasion efficiency. Association between EC strains and
      listeriosis outbreaks may involve characteristics other than virulence
      phenotypes, including survival and growth in food-associated environments.

PMID- 19581478
TI  - Norovirus distribution within an estuarine environment.
AB  - Human norovirus (NoV) has been studied extensively as an important cause of
      gastroenteritis outbreaks worldwide. While oysters are a primary vehicle for
      infection, few studies have examined the wider distribution of NoV in the
      estuarine environment. Active shellfish-harvesting areas in Georgia were examined
      for the prevalence, genotype diversity, and concentrations of NoV in a variety of
      estuarine sample types over the course of 1 year. Of the 225 samples (9 oyster,
      72 water, 72 63- to 200-microm plankton, and 72 >200-microm plankton) collected
      from 12 stations across two estuaries, 21 samples (9.3%) tested positive for NoV.
      By sample type, 55.0% (5/9) of oysters, 8.3% (6/72) of water samples, 11.1%
      (8/72) of 63- to 200-microm plankton samples, and 2.8% (2/72) of >200-microm
      plankton samples were positive for human NoV. The two NoV-positive >200-microm
      plankton samples, which contained mainly zooplankton, had the greatest quantity
      of NoV genomes (3.5 x 10(13) and 1.7 x 10(15) genomes g(-1)) of any sample
      tested. The majority, 90.5% (19/21), of the samples tested positive for genogroup
      I NoV, and only 9.5% (2/21) of the samples tested positive for genogroup II. The
      high concentrations of NoV in plankton samples compared to water and oyster
      samples were unexpected and provide new insights into the presence and
      distribution of human NoV in the water environment.

PMID- 19581479
TI  - Protein engineering of the transcriptional activator FhlA To enhance hydrogen
      production in Escherichia coli.
AB  - Escherichia coli produces H(2) from formate via the formate hydrogenlyase (FHL)
      complex during mixed acid fermentation; the FHL complex consists of formate
      dehydrogenase H (encoded by fdhF) for forming 2H(+), 2e(-), and CO(2) from
      formate and hydrogenase 3 (encoded by hycGE) for synthesizing H(2) from 2H(+) and
      2e(-). FHL protein production is activated by the sigma(54) transcriptional
      activator FhlA, which activates transcription of fdhF and the hyc, hyp, and hydN
      hypF operons. Here, through random mutagenesis using error-prone PCR over the
      whole gene, as well as over the fhlA region encoding the first 388 amino acids of
      the 692-amino-acid protein, we evolved FhlA to increase H(2) production. The
      amino acid replacements in FhlA133 (Q11H, L14V, Y177F, K245R, M288K, and I342F)
      increased hydrogen production ninefold, and the replacements in FhlA1157 (M6T,
      S35T, L113P, S146C, and E363K) increased hydrogen production fourfold. Saturation
      mutagenesis at the codons corresponding to the amino acid replacements in FhlA133
      and at position E363 identified the importance of position L14 and of E363 for
      the increased activity; FhlA with replacements L14G and E363G increased hydrogen
      production (fourfold and sixfold, respectively) compared to FhlA. Whole
      transcriptome and promoter reporter constructs revealed that the mechanism by
      which the FhlA133 changes increase hydrogen production is by increasing
      transcription of all of the genes activated by FhlA (the FHL complex). With
      FhlA133, transcription of P(fdhF) and P(hyc) is less sensitive to formate
      regulation, and with FhlA363 (E363G), P(hyc) transcription increases but P(hyp)
      transcription decreases and hydrogen production is less affected by the repressor
      HycA.

PMID- 19581474
TI  - Potentially pathogenic bacteria in shower water and air of a stem cell transplant
      unit.
AB  - Potential pathogens from shower water and aerosolized shower mist (i.e., shower
      aerosol) have been suggested as an environmental source of infection for
      immunocompromised patients. To quantify the microbial load in shower water and
      aerosol samples, we used culture, microscopic, and quantitative PCR methods to
      investigate four shower stalls in a stem cell transplant unit at Barnes-Jewish
      Hospital in St. Louis, MO. We also tested membrane-integrated showerheads as a
      possible mitigation strategy. In addition to quantification, a 16S rRNA gene
      sequencing survey was used to characterize the abundant bacterial populations
      within shower water and aerosols. The average total bacterial counts were 2.2 x
      10(7) cells/liter in shower water and 3.4 x 10(4) cells/m(3) in shower aerosol,
      and these counts were reduced to 6.3 x 10(4) cells/liter (99.6% efficiency) and
      8.9 x 10(3) cells/m(3) (82.4% efficiency), respectively, after membrane
      integrated showerheads were installed. Potentially pathogenic organisms were
      found in both water and aerosol samples from the conventional showers. Most
      notable was the presence of Mycobacterium mucogenicum (99.5% identity) in the
      water and Pseudomonas aeruginosa (99.3% identity) in the aerosol samples.
      Membrane-integrated showerheads may protect immunocompromised patients from
      waterborne infections in a stem cell transplant unit because of efficient capture
      of vast numbers of potentially pathogenic bacteria from hospital water. However,
      an in-depth epidemiological study is necessary to investigate whether membrane
      integrated showerheads reduce hospital-acquired infections. The microbial load in
      shower aerosols with conventional showerheads was elevated compared to the load
      in HEPA-filtered background air in the stem cell unit, but it was considerably
      lower than typical indoor air. Thus, in shower environments without HEPA
      filtration, the increase in microbial load due to shower water aerosolization
      would not have been distinguishable from anticipated variations in background
      levels.

PMID- 19581480
TI  - Single nucleotide polymorphism-based diagnostic system for crop-associated
      Sclerotinia species.
AB  - A molecular diagnostic system using single nucleotide polymorphisms (SNPs) was
      developed to identify four Sclerotinia species: S. sclerotiorum (Lib.) de Bary,
      S. minor Jagger, S. trifoliorum Erikss., and the undescribed species Sclerotinia
      species 1. DNAs of samples are hybridized with each of five 15-bp oligonucleotide
      probes containing an SNP site midsequence unique to each species. For additional
      verification, hybridizations were performed using diagnostic single nucleotide
      substitutions at a 17-bp sequence of the calmodulin locus. The accuracy of these
      procedures was compared to that of a restriction fragment length polymorphism
      (RFLP) method based on Southern hybridizations of EcoRI-digested genomic DNA
      probed with the ribosomal DNA-containing plasmid probe pMF2, previously shown to
      differentiate S. sclerotiorum, S. minor, and S. trifoliorum. The efficiency of
      the SNP-based assay as a diagnostic test was evaluated in a blind screening of 48
      Sclerotinia isolates from agricultural and wild hosts. One isolate of Botrytis
      cinerea was used as a negative control. The SNP-based assay accurately identified
      96% of Sclerotinia isolates and could be performed faster than RFLP profiling
      using pMF2. This method shows promise for accurate, high-throughput species
      identification.

PMID- 19581481
TI  - Establishment of Agrobacterium tumefaciens-mediated transformation of an
      oleaginous fungus, Mortierella alpina 1S-4, and its application for
      eicosapentaenoic acid producer breeding.
AB  - Gene manipulation tools for an arachidonic-producing filamentous fungus,
      Mortierella alpina 1S-4, have not been sufficiently developed. In this study,
      Agrobacterium tumefaciens-mediated transformation (ATMT) was investigated for M.
      alpina 1S-4 transformation, using the uracil-auxotrophic mutant (ura5(-) strain)
      of M. alpina 1S-4 as a host strain and the homologous ura5 gene as a selectable
      marker gene. Furthermore, the gene for omega3-desaturase, catalyzing the
      conversion of n-6 fatty acid to n-3 fatty acid, was overexpressed in M. alpina 1S
      4 by employing the ATMT system. As a result, we revealed that the frequency of
      transformation surpassed 400 transformants/10(8) spores, most of the integrated T
      DNA appeared as a single copy at a random position in chromosomal DNA, and most
      of the transformants (60 to 80%) showed mitotic stability. Moreover, the
      accumulation of n-3 fatty acid in transformants was observed under the conditions
      of optimal omega3-desaturase gene expression. In particular, eicosapentaenoic
      acid (20:5n-3), an end product of n-3 fatty acids synthesized in M. alpina 1S-4,
      reached a maximum of 40% of total fatty acids. In conclusion, the ATMT system was
      found to be effective and suitable for the industrial strain Mortierella alpina
      1S-4 and will be a useful tool for basic mutagenesis research and for industrial
      breeding of this strain.

PMID- 19581483
TI  - Development of an improved isolation approach and simple sequence repeat markers
      to characterize Phytophthora capsici populations in irrigation ponds in southern
      Georgia.
AB  - Phytophthora capsici, the causal agent of Phytophthora blight, is a major concern
      in vegetable production in Georgia and many other states in the United States.
      Contamination of irrigation water sources by P. capsici may be an important
      source of inoculum for the pathogen. A simple method was developed in this study
      to improve the efficiency of recovering P. capsici from fruits used as baits in
      irrigation ponds. In contrast to direct isolation on agar plates, infected fruit
      tissues were used to inoculate stems of pepper seedlings, and the infected pepper
      stems were used for isolation on agar plates. With isolation through inoculation
      of pepper stems, the frequency of recovering P. capsici from infected eggplant
      and pear fruits increased from 13.9% to 77.7% and 8.1% to 53.5%, respectively,
      compared with direct isolation on agar plates. P. capsici was isolated from seven
      out of nine irrigation ponds evaluated, with most of the ponds containing both A1
      and A2 mating types and a 4:5 ratio of A1 to A2 when isolates from all ponds were
      calculated. All P. capsici isolates were pathogenic on squash plants, and only a
      small proportion (8.2%) of the isolates were resistant or intermediately
      sensitive to mefenoxam. Simple sequence repeats (SSRs) were identified through
      bioinformatics mining of 55,848 publicly available expressed sequence tags of P.
      capsici in dbEST GenBank. Thirty-one pairs of SSR primers were designed, and SSR
      analysis indicated that the 61 P. capsici isolates from irrigation ponds were
      genetically distinct. Cluster analysis separated the isolates into five genetic
      clusters with no more than two genetic groups in one pond, indicating relatively
      low P. capsici genetic diversity in each pond. The isolation method and SSR
      markers developed for P. capsici in this study could contribute to a more
      comprehensive understanding of the genetic diversity of this important pathogen.

PMID- 19581482
TI  - Application of a short intracellular pH method to flow cytometry for determining
      Saccharomyces cerevisiae vitality.
AB  - The measurement of yeast's intracellular pH (ICP) is a proven method for
      determining yeast vitality. Vitality describes the condition or health of viable
      cells as opposed to viability, which defines living versus dead cells. In
      contrast to fluorescence photometric measurements, which show only average ICP
      values of a population, flow cytometry allows the presentation of an ICP
      distribution. By examining six repeated propagations with three separate growth
      phases (lag, exponential, and stationary), the ICP method previously established
      for photometry was transferred successfully to flow cytometry by using the pH
      dependent fluorescent probe 5,6-carboxyfluorescein. The correlation between the
      two methods was good (r(2) = 0.898, n = 18). With both methods it is possible to
      track the course of growth phases. Although photometry did not yield significant
      differences between exponentially and stationary phases (P = 0.433), ICP via flow
      cytometry did (P = 0.012). Yeast in an exponential phase has a unimodal ICP
      distribution, reflective of a homogeneous population; however, yeast in a
      stationary phase displays a broader ICP distribution, and subpopulations could be
      defined by using the flow cytometry method. In conclusion, flow cytometry yielded
      specific evidence of the heterogeneity in vitality of a yeast population as
      measured via ICP. In contrast to photometry, flow cytometry increases information
      about the yeast population's vitality via a short measurement, which is suitable
      for routine analysis.

PMID- 19581484
TI  - Cloning of a novel pyrethroid-hydrolyzing carboxylesterase gene from Sphingobium
      sp. strain JZ-1 and characterization of the gene product.
AB  - A novel esterase gene, pytH, encoding a pyrethroid-hydrolyzing carboxylesterase
      was cloned from Sphingobium sp. strain JZ-1. The gene contained an open reading
      frame of 840 bp. Sequence identity searches revealed that the deduced enzyme
      shared the highest similarity with many alpha/beta-hydrolase fold proteins (20 to
      24% identities). PytH was expressed in Escherichia coli BL21 and purified using
      Ni-nitrilotriacetic acid affinity chromatography. It was a monomeric structure
      with a molecular mass of approximately 31 kDa and a pI of 4.85. PytH was able to
      transform p-nitrophenyl esters of short-chain fatty acids and a wide range of
      pyrethroid pesticides, and isomer selectivity was not observed. No cofactors were
      required for enzyme activity.

PMID- 19581485
TI  - High definition profiling of mammalian DNA methylation by array capture and
      single molecule bisulfite sequencing.
AB  - DNA methylation stabilizes developmentally programmed gene expression states.
      Aberrant methylation is associated with disease progression and is a common
      feature of cancer genomes. Presently, few methods enable quantitative, large
      scale, single-base resolution mapping of DNA methylation states in desired
      regions of a complex mammalian genome. Here, we present an approach that combines
      array-based hybrid selection and massively parallel bisulfite sequencing to
      profile DNA methylation in genomic regions spanning hundreds of thousands of
      bases. This single molecule strategy enables methylation variable positions to be
      quantitatively examined with high sampling precision. Using bisulfite capture, we
      assessed methylation patterns across 324 randomly selected CpG islands (CGI)
      representing more than 25,000 CpG sites. A single lane of Illumina sequencing
      permitted methylation states to be definitively called for >90% of target sties.
      The accuracy of the hybrid-selection approach was verified using conventional
      bisulfite capillary sequencing of cloned PCR products amplified from a subset of
      the selected regions. This confirmed that even partially methylated states could
      be successfully called. A comparison of human primary and cancer cells revealed
      multiple differentially methylated regions. More than 25% of islands showed
      complex methylation patterns either with partial methylation states defining the
      entire CGI or with contrasting methylation states appearing in specific regional
      blocks within the island. We observed that transitions in methylation state often
      correlate with genomic landmarks, including transcriptional start sites and
      intron-exon junctions. Methylation, along with specific histone marks, was
      enriched in exonic regions, suggesting that chromatin states can foreshadow the
      content of mature mRNAs.

PMID- 19581488
TI  - The challenge of predicting and preventing sudden cardiac death immediately after
      myocardial infarction.

PMID- 19581486
TI  - Transcriptional and post-transcriptional profile of human chromosome 21.
AB  - Recent studies have demonstrated extensive transcriptional activity across the
      human genome, a substantial fraction of which is not associated with any
      functional annotation. However, very little is known regarding the post
      transcriptional processes that operate within the different classes of RNA
      molecules. To characterize the post-transcriptional properties of expressed
      sequences from human chromosome 21 (HSA21), we separated RNA molecules from three
      cell lines (GM06990, HeLa S3, and SK-N-AS) according to their ribosome content by
      sucrose gradient fractionation. Polyribosomal-associated RNA and total RNA were
      subsequently hybridized to genomic tiling arrays. We found that approximately 50%
      of the transcriptional signals were located outside of annotated exons and were
      considered as TARs (transcriptionally active regions). Although TARs were
      observed among polysome-associated RNAs, RT-PCR and RACE experiments revealed
      that approximately 40% were likely to represent nonspecific cross-hybridization
      artifacts. Bioinformatics discrimination of TARs according to conservation and
      sequence complexity allowed us to identify a set of high-confidence TARs. This
      set of TARs was significantly depleted in the polysomes, suggesting that it was
      not likely to be involved in translation. Analysis of polysome representation of
      RefSeq exons showed that at least 15% of RefSeq transcripts undergo significant
      post-transcriptional regulation in at least two of the three cell lines tested.
      Among the regulated transcripts, enrichment analysis revealed an over
      representation of genes involved in Alzheimer's disease (AD), including APP and
      the BACE1 protease that cleaves APP to produce the pathogenic beta 42 peptide. We
      demonstrate that the combination of RNA fractionation and tiling arrays is a
      powerful method to assess the transcriptional and post-transcriptional properties
      of genomic regions.

PMID- 19581489
TI  - The impact of a well structured vascular registry in assessing the long-term
      survival after repair of abdominal aortic aneurysms.

PMID- 19581487
TI  - High-resolution analysis of epigenetic changes associated with X inactivation.
AB  - Differentiation of female murine ES cells triggers silencing of one X chromosome
      through X-chromosome inactivation (XCI). Immunofluorescence studies showed that
      soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic
      changes, including the acquisition of H3K27me3. However, the mechanisms that lead
      to the establishment of heterochromatin remain unclear. We first analyze
      chromatin changes by ChIP-chip, as well as RNA expression, around the X
      inactivation center (Xic) in female and male ES cells, and their day 4 and 10
      differentiated derivatives. A dynamic epigenetic landscape is observed within the
      Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its
      promoter during differentiation of both female and male cells. However, only in
      female cells does an active epigenetic landscape emerge at the Xist locus,
      concomitant with high Xist expression. Several regions within and around the Xic
      show unsuspected chromatin changes, and we define a series of unusual loci
      containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female
      specific quantitative increase of H3K27me3 across the X chromosome as XCI
      proceeds in differentiating female ES cells. Using female ES cells with nonrandom
      XCI and polymorphic X chromosomes, we demonstrate that this increase is specific
      to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes
      evenly associated with the Xi in a chromosome-wide fashion. A selective and
      robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over
      active genes. This indicates that deposition of H3K27me3 during XCI is tightly
      associated with the act of silencing of individual genes across the Xi.

PMID- 19581490
TI  - Assays for S-nitrosothiols and S-nitrosylated proteins and mechanistic insights
      into cardioprotection.

PMID- 19581491
TI  - Estrogen receptor-beta activation results in S-nitrosylation of proteins involved
      in cardioprotection.
AB  - BACKGROUND: It has been shown that the activation of estrogen receptor-beta (ER
      beta) plays an important cardioprotective role against ischemia/reperfusion
      injury. However, the mechanism for this protection is not clear. We hypothesize
      that estrogen protects by ER-beta activation, which leads to S-nitrosylation
      (SNO) of key cardioprotective proteins. METHODS AND RESULTS: We treated
      ovariectomized C57BL/6J mice with the ER-beta selective agonist 2,2-bis(4
      hydroxyphenyl)-proprionitrile (DPN), 17beta-estradiol (E2), or vehicle using
      Alzet minipumps for 2 weeks. Isolated hearts were Langendorff perfused and
      subjected to ischemia and reperfusion. Compared with vehicle-treated hearts, DPN-
      and E2-treated hearts had significantly better postischemic functional recovery
      and decreased infarct size. To test the specificity of DPN, we treated ER-beta
      knockout mice with DPN. However, no cardioprotective effect of DPN was found in
      ER-beta-knockout mice, indicating that the DPN-induced cardioprotection occurs
      through the activation of ER-beta. Using DyLight-maleimide fluors and a modified
      biotin switch method, we used a 2-dimensional DyLight fluorescence difference gel
      electrophoresis proteomic method to quantify differences in SNO of proteins. DPN-
      and E2-treated hearts showed an increase in SNO of a number of proteins.
      Interestingly, many of these proteins also had been shown to have increased SNO
      in preconditioned hearts. In addition, the DPN-induced cardioprotection and
      increased SNO were abolished by treatment with a nitric oxide synthase inhibitor.
      CONCLUSIONS: The activation of ER-beta by DPN treatment leads to increased
      protein SNO and cardioprotection against ischemia/reperfusion injury, suggesting
      that long-term estrogen exposure protects hearts largely via activation of ER
      beta and nitric oxide/SNO signaling.

PMID- 19581492
TI  - Role of pulse oximetry in examining newborns for congenital heart disease: a
      scientific statement from the American Heart Association and American Academy of
      Pediatrics.
AB  - BACKGROUND: The purpose of this statement is to address the state of evidence on
      the routine use of pulse oximetry in newborns to detect critical congenital heart
      disease (CCHD). METHODS AND RESULTS: A writing group appointed by the American
      Heart Association and the American Academy of Pediatrics reviewed the available
      literature addressing current detection methods for CCHD, burden of missed and/or
      delayed diagnosis of CCHD, rationale of oximetry screening, and clinical studies
      of oximetry in otherwise asymptomatic newborns. MEDLINE database searches from
      1966 to 2008 were done for English-language papers using the following search
      terms: congenital heart disease, pulse oximetry, physical examination, murmur,
      echocardiography, fetal echocardiography, and newborn screening. The reference
      lists of identified papers were also searched. Published abstracts from major
      pediatric scientific meetings in 2006 to 2008 were also reviewed. The American
      Heart Association classification of recommendations and levels of evidence for
      practice guidelines were used. In an analysis of pooled studies of oximetry
      assessment performed after 24 hours of life, the estimated sensitivity for
      detecting CCHD was 69.6%, and the positive predictive value was 47.0%; however,
      sensitivity varied dramatically among studies from 0% to 100%. False-positive
      screens that required further evaluation occurred in only 0.035% of infants
      screened after 24 hours. CONCLUSIONS: Currently, CCHD is not detected in some
      newborns until after their hospital discharge, which results in significant
      morbidity and occasional mortality. Furthermore, routine pulse oximetry performed
      on asymptomatic newborns after 24 hours of life, but before hospital discharge,
      may detect CCHD. Routine pulse oximetry performed after 24 hours in hospitals
      that have on-site pediatric cardiovascular services incurs very low cost and risk
      of harm. Future studies in larger populations and across a broad range of newborn
      delivery systems are needed to determine whether this practice should become
      standard of care in the routine assessment of the neonate.

PMID- 19581493
TI  - Trends in cardiovascular disease risk factors in individuals with and without
      diabetes mellitus in the Framingham Heart Study.
AB  - BACKGROUND: Individuals with diabetes mellitus are at 2- to 3-fold increased risk
      for cardiovascular disease (CVD) relative to those without diabetes. Our
      objective was to examine CVD risk factor level changes among individuals with and
      without type 2 diabetes mellitus from 1970 to 2005 in the Framingham Heart Study.
      METHODS AND RESULTS: We included 4195 participants (3990 with no diabetes and 205
      with diabetes) 50 years of age and 3495 participants (3178 with no diabetes and
      317 with diabetes) 60 years of age. Contemporaneous CVD risk factor levels were
      measured; linear regression models were used to assess the interaction between
      diabetes status and calendar year on CVD risk factor levels. Among 50-year-olds
      without diabetes mellitus, there was an increase in body mass index of 0.39
      kg/m(2) per 10 years, whereas for those with diabetes, there was an increase of
      2.52 kg/m(2) (P value for the diabetes-by-calendar year interaction [P for
      interaction] <0.001). For low-density lipoprotein cholesterol, the mean decrease
      was -7.43 mg/dL per decade (nondiabetes) and -15.5 mg/dL for diabetes (P for
      interaction=0.002). For systolic blood pressure, the mean decrease was -3.35 mm
      Hg per decade (nondiabetes) and -3.50 mm Hg for diabetes (P for
      interaction=0.97). The direction of the trends for those with diabetes relative
      to those without diabetes was similar for 60-year-olds. CONCLUSIONS: Compared
      with individuals without diabetes mellitus, individuals with diabetes experienced
      a greater increase in body mass index, a greater decrease in low-density
      lipoprotein cholesterol, and a similar magnitude of decline in systolic blood
      pressure. Individuals with diabetes mellitus have not experienced the necessary
      declines in CVD risk factors to overcome their increased risk of CVD. Further
      efforts are needed to aggressively control CVD risk factors among individuals
      with diabetes mellitus.

PMID- 19581494
TI  - Conventional cardiovascular risk factors and metabolic syndrome in predicting
      carotid intima-media thickness progression in young adults: the cardiovascular
      risk in young Finns study.
AB  - BACKGROUND: Conventional risk factors and metabolic syndrome (MetS) are cross
      sectionally associated with subclinical atherosclerosis in young adults. We
      evaluated the relations of conventional risk factors and MetS to the 6-year
      progression of carotid intima-media thickness (IMT) in a population of young
      adults. RESULTS AND METHODS: The study included 1809 subjects (aged 32+/-5 years)
      who had IMT measured in 2001 and 2007. Risk factor measurements included low
      density lipoprotein cholesterol, body mass index, C-reactive protein, smoking,
      and family history of coronary disease in addition to MetS components. We used
      European Group for the Study of Insulin Resistance, revised National Cholesterol
      Education Program, and International Diabetes Federation definitions to diagnose
      MetS in 2001. Waist circumference (P<0.0001), low-density lipoprotein cholesterol
      (P=0.01), and insulin (P=0.003) were directly associated with IMT progression in
      a multivariable model adjusted for age, sex, and baseline IMT (model R(2)=24%).
      When the MetS/European Group for the Study of Insulin Resistance definition was
      included in the model, it was directly associated with IMT progression (P=0.03),
      but its inclusion did not improve the model's predictive value. IMT increased
      79+/-7 mum (mean+/-SEM) in subjects with MetS according to the MetS/European
      Group for the Study of Insulin Resistance definition and 42+/-2 mum in subjects
      without MetS (P<0.0001). In addition, the number of MetS components was linearly
      associated with IMT progression (P<0.0001). Similar results were seen with
      MetS/revised National Cholesterol Education Program and MetS/International
      Diabetes Federation definitions. CONCLUSIONS: Obesity, high low-density
      lipoprotein cholesterol, and high insulin level predicted IMT progression in
      young adults. All MetS definitions identified young adults with accelerated IMT
      progression, but we found no evidence that MetS would predict IMT progression
      more than expected from the sum of its risk components.

PMID- 19581495
TI  - Glutamic acid, the main dietary amino acid, and blood pressure: the INTERMAP
      Study (International Collaborative Study of Macronutrients, Micronutrients and
      Blood Pressure).
AB  - BACKGROUND: Data are available that indicate an independent inverse relationship
      of dietary vegetable protein to the blood pressure (BP) of individuals. Here, we
      assess whether BP is associated with glutamic acid intake (the predominant
      dietary amino acid, especially in vegetable protein) and with each of 4 other
      amino acids that are relatively higher in vegetable than animal protein (proline,
      phenylalanine, serine, and cystine). METHODS AND RESULTS: This was a cross
      sectional epidemiological study with 4680 persons 40 to 59 years of age from 17
      random population samples in China, Japan, the United Kingdom, and the United
      States. BP was measured 8 times at 4 visits; dietary data (83 nutrients, 18 amino
      acids) were obtained from 4 standardized, multipass, 24-hour dietary recalls and
      2 timed 24-hour urine collections. Dietary glutamic acid (percentage of total
      protein intake) was inversely related to BP. Across multivariate regression
      models (model 1, which controlled for age, gender, and sample, through model 5,
      which controlled for 16 possible nonnutrient and nutrient confounders), estimated
      average BP differences associated with a glutamic acid intake that was higher by
      4.72% of total dietary protein (2 SD) were -1.5 to -3.0 mm Hg systolic and -1.0
      to -1.6 mm Hg diastolic (z scores -2.15 to -5.11). Results were similar for the
      glutamic acid-BP relationship with each of the other amino acids also in the
      model; eg, with control for 15 variables plus proline, systolic/diastolic
      pressure differences were -2.7/-2.0 mm Hg (z scores -2.51, -2.82). In these 2
      amino acid models, higher intake (by 2 SD) of each of the other amino acids was
      associated with small BP differences and z scores. CONCLUSIONS: Dietary glutamic
      acid may have independent BP-lowering effects, which may contribute to the
      inverse relation of vegetable protein to BP.

PMID- 19581496
TI  - Outcomes of early risk stratification and targeted implantable cardioverter
      defibrillator implantation after ST-elevation myocardial infarction treated with
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Methods to identify high-risk patients and timing of implantable
      cardioverter-defibrillator (ICD) therapy after ST-elevation myocardial infarction
      need further optimization. METHODS AND RESULTS: We evaluated outcomes of early
      ICD implantation in patients with inducible ventricular tachycardia. Consecutive
      patients treated with primary percutaneous coronary intervention for acute ST
      elevation myocardial infarction underwent early left ventricular ejection
      fraction (LVEF) assessment. Patients with LVEF >40% were discharged (group 1);
      patients with LVEF < or =40% underwent risk stratification with
      electrophysiological study. If no ventricular tachycardia was induced, patients
      were discharged without an ICD (group 2). If sustained monomorphic ventricular
      tachycardia (> or =200-ms cycle length) was induced, an ICD was implanted before
      discharge (group 3). Follow-up was obtained up to 30 months in all patients and
      up to 48 months in a subgroup of patients with LVEF < or =30% without an ICD. The
      primary end point was total mortality. Group 1 (n=574) had a mean LVEF of 54+/
      8%; group 2 (n=83), 32+/-6%; and group 3 (n=32), 29+/-7%. At a median follow-up
      of 12 months, there was no significant difference in survival between the 3
      groups (P=0.879), with mortality rates of 3%, 3%, and 6% for groups 1 through 3,
      respectively. In the subgroup of group 2 patients with LVEF < or =30% and no ICD
      (n=25), there was 9% mortality at a median follow-up of 25 months. In group 3,
      19% had spontaneous ICD activation resulting from ventricular tachycardia.
      CONCLUSIONS: Early ICD implantation limited to patients with inducible
      ventricular tachycardia enables a low overall mortality in patients with impaired
      LVEF after primary percutaneous coronary intervention for ST-elevation myocardial
      infarction.

PMID- 19581497
TI  - Improved long-term survival after abdominal aortic aneurysm repair.
AB  - BACKGROUND: Treatment of abdominal aortic aneurysm (AAA) has changed
      significantly over the past 2 decades. In this perspective, time trends in long
      term survival were studied. METHODS AND RESULTS: We identified 8663 primary
      intact and 4171 ruptured AAA repairs in the Swedish Vascular Registry from 1987
      to 2005. Mortality was obtained from the national population registry. Crude
      survival was analyzed, including all mortality. To analyze the long-term outcome
      among those surviving the AAA repair, relative survival, which denotes the
      survival rate of patients compared with that of the general population adjusted
      for age, sex, and calendar year, was calculated, excluding 90-day mortality. In a
      comparison of AAA repairs from 1987 to 1999 and 2000 to 2005, age (71.4 versus
      72.5 years; P<0.001), patients with comorbidities (65.0% versus 68.5%; P<0.001),
      and endovascular repair (1.6% versus 17.0%; P<0.001) increased. After intact AAA
      repair, crude 5-year survival was 69.0% (99% confidence interval [CI], 67.7 to
      70.4), and relative 5-year survival excluding 90-day mortality was 90.3% (99% CI,
      88.6 to 92.0). Relative 5-year survival was better for those operated on from
      2000 to 2005 compared with 1987 to 1999 (difference, 4.7%; 99% CI, 1.3 to 8.1),
      for men versus women (4.6%; 99% CI, 0.4 to 8.8), and for octogenarians versus
      patients <80 years of age (10.2%; 99% CI, 1.5 to 18.8); no difference was
      observed between open and endovascular repair (6.0%; 99% CI, -1.5 to 13.4). After
      ruptured AAA repair, crude 5-year survival was 41.7% (99% CI, 39.6 to 43.7) and
      relative 5-year survival was 87.1% (99% CI, 83.9 to 90.3). No significant
      differences in relative 5-year survival were observed between time periods, sex,
      or age groups. CONCLUSIONS: Long-term survival improved over time after intact
      AAA repair despite a change in case mix toward older patients with more
      comorbidities. Long-term survival was stable after ruptured AAA repair.

PMID- 19581498
TI  - Sodium chloride and aldosterone: harbingers of hypertension-related
      cardiovascular disease.

PMID- 19581499
TI  - Tumor necrosis factor-alpha--converting enzyme roles in hypertension-induced
      hypertrophy: look both ways when crossing the street.

PMID- 19581500
TI  - Nocturia, nocturnal activity, and nondipping.
AB  - Patients with chronic kidney disease have less than expected decline in blood
      pressure during sleep (nondipping) and commonly experience the vexing symptom of
      nocturia. To better understand the relationship among nocturia, nighttime
      physical activity, and nondipping, we studied 98 patients with chronic kidney
      disease on 2 occasions, 1 month apart, with 24-hour ambulatory blood pressure
      monitoring and simultaneous activity monitoring with wrist actigraphy. Patients
      with nocturia had greater actigraphically recorded nighttime physical activity
      compared to those with no nocturia. The drop in activity from wake to sleep was
      reduced to a similar extent whether the patients had nocturia once or twice, but
      patients who had nocturia >/=3 times had the least reduction from wake to sleep
      activity (P<0.001 versus those with less degrees of nocturia). Those with
      nocturia had a lesser drop in systolic ambulatory blood pressure during sleep
      compared with those without nocturia. The average fall in sleep systolic blood
      pressure was 9.8 mm Hg (95% CI: 8.0 to 11.6 mm Hg) in those without nocturia
      compared with 3.4 mm Hg (95% CI: 2.7 to 4.1 mm Hg) in those with any severity of
      nocturia (P<0.001 for difference). Nondipping in patients with nocturia was
      mediated by nighttime physical activity. These differences were independent of
      estimated glomerular filtration rate, albuminuria, or use of diuretics. Thus,
      nocturia, which may reflect impaired renal tubular function, is associated with
      nondipping in patients with chronic kidney disease and appears to be mediated by
      increased nocturnal activity. Whether nocturia itself or the resulting nondipping
      associated with nocturia is of prognostic importance for cardiorenal events in
      patients with chronic kidney disease should be tested in future studies.

PMID- 19581501
TI  - Have no fear, MitoQ10 is here.

PMID- 19581503
TI  - Angiotensin-converting enzyme and dipeptidyl peptidase IV inhibitors: an
      increased risk of angioedema.

PMID- 19581502
TI  - Critical role of apoptosis signal-regulating kinase 1 in aldosterone/salt-induced
      cardiac inflammation and fibrosis.
AB  - The molecular mechanism underlying aldosterone/salt-induced cardiovascular injury
      remains to be defined. This work was undertaken to determine the role of
      apoptosis signal-regulating kinase 1 (ASK1) in the mechanism underlying
      aldosterone-induced cardiac injury in vivo. We compared the in vivo effects of 4
      weeks of aldosterone/salt treatment on wild-type and ASK1-deficient mice.
      Aldosterone infusion plus high salt intake in wild-type mice significantly
      increased blood pressure and urinary albumin excretion and decreased plasma
      potassium concentrations, and these effects of aldosterone/salt were not affected
      by ASK1 deficiency. Thus, ASK1 seems to play a minor role in aldosterone-induced
      hypertension and renal injury. ASK1 deficiency also failed to affect aldosterone
      induced cardiac hypertrophy. However, ASK1 deficiency markedly ameliorated
      aldosterone-induced cardiac injury, eg, the enhancement of cardiac macrophage
      infiltration, monocyte chemotactic protein 1 expression, interstitial fibrosis,
      perivascular fibrosis, and transforming growth factor-beta1 and collagen type I
      expressions. Thus, ASK1 participates in aldosterone-induced cardiac inflammation
      and fibrosis. Furthermore, the enhancement of NADPH oxidase-mediated cardiac
      oxidative stress caused by aldosterone infusion was markedly lessened by ASK1
      deficiency, which was associated with the significant amelioration by ASK1
      deficiency of aldosterone-induced cardiac Nox2 upregulation. Furthermore,
      aldosterone/salt treatment significantly enhanced cardiac expression of the
      angiotensin-converting enzyme and angiotensin II type 1 receptor in wild-type
      mice, whereas the enhancement of these proteins by aldosterone/salt was abolished
      by ASK1 deficiency. Our results demonstrate that ASK1 is implicated in
      aldosterone/salt-induced cardiac inflammation and fibrosis through the
      enhancement of NADPH oxidase-mediated oxidative stress and the upregulation of
      the cardiac renin-angiotensin system.

PMID- 19581504
TI  - Role of body size on cardiovascular function: can we see the meat through the
      fat?

PMID- 19581505
TI  - Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE
      inhibitor-associated angioedema.
AB  - Dipeptidyl peptidase-IV (DPP-IV) inhibitors decrease degradation of the
      incretins. DPP-IV inhibitors also decrease degradation of peptides, such as
      substance P, that may be involved in the pathogenesis of angiotensin-converting
      enzyme (ACE) inhibitor-associated angioedema. This study tested the hypothesis
      that DPP-IV inhibition affects risk of clinical angioedema, by comparing the
      incidence of angioedema in patients treated with the DPP-IV inhibitor
      vildagliptin versus those treated with comparator in Phase III randomized
      clinical trials. Prospectively defined angioedema-related events were adjudicated
      in a blinded fashion by an internal medicine adjudication committee and expert
      reviewer. Concurrent ACE inhibitor or angiotensin receptor blocker exposure was
      ascertained from case report forms. Study drug exposure was ascertained from
      unblinded data from phase III studies. Odds ratios and 95% confidence intervals
      comparing angioedema risk in vildagliptin-treated and comparator-treated patients
      were calculated for the overall population and for patients taking ACE inhibitors
      or angiotensin receptor blockers, using both an analysis of pooled data and a
      meta-analysis (Peto method). Overall, there was no association between
      vildagliptin use and angioedema. Among individuals taking an ACE inhibitor,
      however, vildagliptin use was associated with an increased risk of angioedema (14
      confirmed cases among 2754 vildagliptin users versus 1 case among 1819 comparator
      users: odds ratio 4.57 [95% confidence interval 1.57 to 13.28]) in the meta
      analysis. Vildagliptin use may be associated with increased risk of angioedema
      among patients taking ACE inhibitors, although absolute risk is small. Physicians
      confronted with angioedema in a patient taking an ACE inhibitor and DPP-IV
      inhibitor should consider this possible drug-drug interaction.

PMID- 19581506
TI  - Intensifying therapy for hypertension despite suboptimal adherence.
AB  - More intensive management can improve control blood pressure (BP) in hypertensive
      patients. However, many would posit that treatment intensification (TI) is not
      beneficial in the face of suboptimal adherence. We investigated whether the
      effect of TI on BP varies by adherence. We enrolled 819 patients with
      hypertension, managed in primary care at an academically-affiliated inner-city
      hospital. We used the following formula to characterize TI: (visits with a
      medication change-visits with elevated BP)/total visits. Adherence was
      characterized using electronic monitoring devices ("MEMS caps"). Patients who
      returned their MEMS caps (671) were divided into quartiles of adherence, whereas
      patients who did not return their MEMS caps (148) had "missing" adherence. We
      examined the relationship between TI and the final systolic blood pressure (SBP),
      controlling for patient-level covariates. In the entire sample, each additional
      therapy increase per 10 visits predicted a 2.0 mm Hg decrease in final SBP
      (P<0.001). After stratifying by adherence, in the "best" adherence quartile each
      therapy increase predicted a 2.1-mm Hg decrease in final SBP, followed by 1.8 for
      the "next-best" adherence quartile, 2.3 in the third quartile, and 2.4 in the
      "worst" adherence quartile. The effect size for patients with "missing" adherence
      was 1.6 mm Hg. The differences between the group with "best" adherence and the
      other 4 groups were not statistically significant. In this observational study,
      treatment intensification was associated with similar BP improvement regardless
      of the patient's level of adherence. A randomized trial could further examine
      optimal management of patients with suboptimal adherence.

PMID- 19581507
TI  - Arterial load and ventricular-arterial coupling: physiologic relations with body
      size and effect of obesity.
AB  - Accurate quantification of arterial function is crucial to distinguishing disease
      states from normal variants. However, there are little data regarding methods to
      scale arterial load to body size in humans. We studied 2365 adults aged 35 to 55
      years free of overt cardiovascular disease. We assessed arterial hemodynamics and
      ventricular-vascular coupling with carotid tonometry and Doppler
      echocardiography. To define normal (physiological) relationships between
      hemodynamic indices and body size, we used nonlinear regression to analyze a
      selected reference subsample (n=612) with normal weight (body mass index 18 to 25
      kg/m(2)), waist circumference, and metabolic parameters. Most arterial
      hemodynamic indices demonstrated important relationships with body size, which
      were frequently allometric (nonlinear). Allometric indexation using appropriate
      powers (but not ratiometric indexation) effectively eliminated the relationships
      between indices of arterial load and body size in normal subjects. In the entire
      sample (n=2365), the adverse effects of obesity on arterial load and end-systolic
      ventricular stiffening were clearly demonstrated only after appropriate
      indexation to account for the expected normal relationship to body size. After
      adjustment for age and sex, a progressive increase in indexed systemic vascular
      resistance, effective arterial and ventricular end-systolic elastance, and a
      decrease in total arterial compliance were seen from normal weight to obesity
      (P<0.0001). Arterial load relates to body size in an allometric fashion, calling
      for scaling with the use of appropriate powers. Obesity exerts adverse effects on
      arterial load and ventricular stiffening that go beyond the normal relationship
      with body size. Allometric normalization should allow more accurate
      quantification of arterial load in future studies.

PMID- 19581508
TI  - Independent relations of left ventricular structure with the 24-hour urinary
      excretion of sodium and aldosterone.
AB  - Previous studies reported on the association of left ventricular mass index
      (LVMI) with urinary sodium or with circulating or urinary aldosterone. We
      investigated the independent associations of LVMI with the urinary excretion of
      both sodium and aldosterone. We randomly recruited 317 untreated subjects from a
      white population (45.1% women; mean age 48.2 years). Measurements included
      echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion
      of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa(prox))
      and distal (RNa(dist)) renal sodium reabsorption, assessed from the endogenous
      lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI
      per 1-SD increase in the explanatory variables, while accounting for sex, age,
      systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently
      with the urinary excretion of both sodium (+2.48 g/m(2); P=0.005) and aldosterone
      (+2.63 g/m(2); P=0.004). Higher sodium excretion was associated with increased
      mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end
      diastolic diameter (LVID: +0.12 mm, P=0.64). In contrast, higher aldosterone
      excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change
      in MWT (+0.070 mm; P=0.28). Higher RNa(dist) was associated with lower relative
      wall thickness (-0.81x10(-2), P=0.017), because of opposite trends in LVID (+0.33
      mm; P=0.13) and MWT (-0.130 mm; P=0.040). LVMI was not associated with PRA or
      RNa(prox.) In conclusion, LVMI independently increased with both urinary sodium
      and aldosterone excretion. Increased MWT explained the association of LVMI with
      urinary sodium and increased LVID the association of LVMI with urinary
      aldosterone.

PMID- 19581509
TI  - Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and
      attenuates cardiac hypertrophy.
AB  - Mitochondria are a major site of reactive oxygen species production, which may
      contribute to the development of cardiovascular disease. Protecting mitochondria
      from oxidative damage should be an effective therapeutic strategy; however,
      conventional antioxidants are ineffective, because they cannot penetrate the
      mitochondria. This study investigated the role of mitochondrial oxidative stress
      during development of hypertension in the stroke-prone spontaneously hypertensive
      rat, using the mitochondria-targeted antioxidant, MitoQ(10). Eight-week-old male
      stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500
      mumol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500
      mumol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood
      pressure was significantly reduced by approximately 25 mm Hg over the 8-week
      MitoQ(10) treatment period compared with decylTPP (F=5.94; P=0.029) or untreated
      controls (F=65.6; P=0.0001). MitoQ(10) treatment significantly improved thoracic
      aorta NO bioavailability (1.16+/-0.03 g/g; P=0.002, area under the curve)
      compared with both untreated controls (0.68+/-0.02 g/g) and decylTPP-treated rats
      (0.60+/-0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ(10)
      treatment compared with untreated control and decylTPP treatment (MitoQ(10):
      4.01+/-0.05 mg/g; control: 4.42+/-0.11 mg/g; and decylTPP: 4.40+/-0.09 mg/g;
      ANOVA P=0.002). Total MitoQ(10) content was measured in liver, heart, carotid
      artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography
      tandem mass spectrometry. All of the organs analyzed demonstrated detectable
      levels of MitoQ(10), with comparable accumulation in vascular and cardiac
      tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10)
      protects against the development of hypertension, improves endothelial function,
      and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive
      rats. MitoQ(10) provides a novel approach to attenuate mitochondrial-specific
      oxidative damage with the potential to become a new therapeutic intervention in
      human cardiovascular disease.

PMID- 19581510
TI  - Regulation of proliferation and membrane potential by chloride currents in rat
      pulmonary artery smooth muscle cells.
AB  - Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to
      increased pulmonary vascular resistance and pulmonary hypertension. Because
      proliferation depends on membrane potential (V(m)) and because V(m) is, in part,
      determined by Cl(-) currents (I(Cl)), we examined the effects of I(Cl) inhibition
      with 4,4;-diisothiocyanatostilbene-2,2;-disulfonic acid (DIDS) on cultured rat
      PASMCs. DIDS (30 mumol/L) reduced cell numbers, decreased 5-bromodeoxyuridine
      incorporation and delayed cell cycle progression. I(Cl) inhibition with 5-Nitro-2
      (3-phenylpropylamino) benzoic acid (100 mumol/L) also reduced cell numbers of
      cultured rat PASMCs. To test the possible involvement of I(Cl) in the regulation
      of PASMC proliferation, we measured V(m) and I(Cl) in both cultured
      (proliferating) and acutely dissociated (nonproliferating) rat PASMCs. V(m) (
      39.3+/-1.4 mV) was close to the equilibrium potential of Cl(-) (-39 mV) in
      proliferating PASMCs but differed from equilibrium potential of Cl(-) in acutely
      dissociated cells (-45.3+/-0.9 mV). DIDS and substitution of extracellular Cl(-)
      with I(-) induced V(m) hyperpolarization in proliferating but not
      nonproliferating PASMCs. Consistent with V(m) recordings, DIDS-sensitive baseline
      and swelling-activated (Ca(2+)-independent) I(Cl)s, recorded with low Ca(2+) (<1
      nmol/L) pipette solutions, were approximately 5-fold greater in proliferating
      than in nonproliferating PASMCs. By contrast, Ca(2+)-activated I(Cl) did not
      differ between proliferating and nonproliferating PASMCs. Ca(2+)-independent
      I(Cl)s were also increased in proliferating PASMCs acutely dissociated from rats
      exposed to hypoxia (10% O(2); 7 days). These findings are consistent with the
      conclusion that I(Cl)s regulate proliferation of PASMCs and suggest that
      selective I(Cl) inhibition may be useful in treating pulmonary hypertension.

PMID- 19581511
TI  - Sodium intake and vascular stiffness in hypertension.

PMID- 19581512
TI  - Tumor necrosis factor-alpha-converting enzyme is a key regulator of agonist
      induced cardiac hypertrophy and fibrosis.
AB  - Cardiac remodeling is associated with hypertrophy and fibrosis processes, which
      may depend on the activity of matrix metalloproteinases (MMPs) and "a disintegrin
      and metalloproteinases" (ADAMs). We investigated whether ADAM-17 (tumor necrosis
      factor-alpha-converting enzyme [TACE]) plays a role in agonist-induced cardiac
      remodeling and the relationships established among TACE, MMP-2, and ADAM-12. We
      targeted TACE in rodent models of spontaneous and agonist-induced hypertension
      using RNA interference combined with quantitative RT-PCR, activity
      determinations, and functional studies. Treatment of spontaneously hypertensive
      rats with previously validated TACE small-interfering RNA for 28 days resulted in
      systemic knockdown of TACE expression. TACE knockdown effectively stopped the
      development of cardiac hypertrophy. Mice receiving angiotensin II (1.4 mg/kg per
      day for 12 days) exhibited cardiac hypertrophy, as well as fibrosis, which was
      associated with elevated myocardial expression of molecular markers of
      hypertrophy (alpha-skeletal actin, beta-myosin heavy chain, and brain natriuretic
      peptide) and fibrosis (collagen types I and III and fibronectin), as well as MMP
      2 and ADAM-12. Treatment with TACE small-interfering RNA (but not with PBS or
      luciferase small-interfering RNA) inhibited TACE expression, thus preventing
      angiotensin II-induced cardiac hypertrophy and fibrosis. Moreover, knockdown of
      TACE inhibited angiotensin II-induced overexpression of markers of myocardial
      hypertrophy and fibrosis, as well as ADAM-12 and MMP-2. These findings provide
      the first in vivo evidence that agonist-induced cardiac hypertrophy and fibrosis
      processes are signaled through TACE, which acts through novel pathways involving
      transcriptional regulation of ADAM-12 and MMP-2. Targeting TACE has potential
      therapeutic importance for modulating agonist-induced cardiac remodeling.

PMID- 19581513
TI  - Home Blood Pressure Measurements Will Not Replace 24-Hour Ambulatory Blood
      Pressure Monitoring.

PMID- 19581514
TI  - Why Is Out-of-Office Blood Pressure Measurement Needed?

PMID- 19581515
TI  - Images in cardiovascular medicine. Uncommon variant of Ebstein anomaly with
      tricuspid stenosis.

PMID- 19581516
TI  - Letter by Testa et al regarding article, "presence of older thrombus is an
      independent predictor of long-term mortality in patients with ST-elevation
      myocardial infarction treated with thrombus aspiration during primary
      percutaneous coronary intervention".

PMID- 19581517
TI  - Letter by Niccoli et al regarding article, "presence of older thrombus is an
      independent predictor of long-term mortality in patients with ST-elevation
      myocardial infarction treated with thrombus aspiration during primary
      percutaneous coronary intervention".

PMID- 19581518
TI  - Letter by Lambertucci and Antunes regarding article, "pulmonary vascular disease
      in the developing world".

PMID- 19581520
TI  - Predicting outcome in patients with asymptomatic aortic stenosis.

PMID- 19581521
TI  - Careers in cardiovascular outcomes research.

PMID- 19581522
TI  - Images in cardiovascular medicine. Loeffler endocarditis mimicking apical
      hypertrophic cardiomyopathy.

PMID- 19581524
TI  - Studying genetic variations in cancer prognosis (and risk): a primer for
      clinicians.
AB  - Rare, high-penetrance genetic variations account for a small portion of genetic
      cancer syndromes. In contrast, most cancers develop from a combination of minor
      genetic influences and environmental factors. There are numerous publications on
      cancer susceptibility. In contrast, genetic studies in treatment response and
      outcome analyses are a rapidly emerging field. Approaches used in disease
      susceptibility can be adapted for genetic outcome studies. In this review, we
      summarize the current knowledge on how candidate genes and genetic variations are
      selected to evaluate gene-outcome, gene-prognosis, and gene-treatment response
      relationships as applicable to the practicing oncologist.

PMID- 19581525
TI  - Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients
      receiving systemic therapy for advanced hepatocellular carcinoma.
AB  - BACKGROUND: The role of serum alpha-fetoprotein (AFP) as a marker for treatment
      response in patients with hepatocellular carcinoma (HCC) receiving systemic
      therapy is poorly defined. METHODS: A retrospective study was performed on
      patients with advanced HCC enrolled in five phase II clinical trials. Serum AFP
      was prospectively collected at baseline and at different time points through
      treatment in parallel with radiologic response and clinical outcome. Patients
      were separated into three groups based on a 50% change in serum AFP from
      baseline. Overall survival (OS), progression-free survival (PFS), and radiologic
      responses were compared between groups using log-rank and Wilcoxon tests.
      RESULTS: Of 144 patients, 107 met the eligibility criteria. Eighteen patients
      experienced a >50% AFP decline, 57 patients had a >50% AFP increase, and 32
      patients had a <50% change in serum AFP in either direction. Compared with
      patients with a <50% change in serum AFP (median PFS, 5.6 months), patients with
      a >50% AFP decrease had a longer PFS time (median, 16.9 months; p = .029),
      whereas those with a >50% increase had a shorter PFS time (median, 2.3 months; p
      = .038). Patients with a >50% rise in AFP had a shorter OS time than those with a
      <50% change (median, 6.3 months versus 11.1 months, respectively; p = .004),
      whereas a >50% AFP decrease was not associated with a significant difference in
      OS (median, 13.0 months; p = .87). AFP changes were significantly associated with
      radiologic response. CONCLUSIONS: Our study suggests that serum AFP change during
      treatment may serve as a useful surrogate marker for clinical outcome in patients
      with advanced HCC receiving systemic therapy.

PMID- 19581523
TI  - The role of Src in solid tumors.
AB  - The proto-oncogene c-Src (Src) encodes a nonreceptor tyrosine kinase whose
      expression and activity are correlated with advanced malignancy and poor
      prognosis in a variety of human cancers. Nine additional enzymes with homology to
      Src have been identified and collectively are referred to as Src family kinases
      (SFKs). Together, SFKs represent the largest family of nonreceptor tyrosine
      kinases and interact directly with receptor tyrosine kinases, G-protein-coupled
      receptors, steroid receptors, signal transducers and activators of transcription,
      and molecules involved in cell adhesion and migration. These interactions lead to
      a diverse array of biological functions including proliferation, cell growth,
      differentiation, cell shape, motility, migration, angiogenesis, and survival.
      Studies investigating mutational activation of Src in human cancers suggest that
      this may be a rare event and that wild-type Src is weakly oncogenic. Thus, the
      role of Src in the development and progression of human cancer remains unclear.
      Recently, it was suggested that increased SFK protein levels and, more
      importantly, SFK tyrosine kinase activity are linked to cancer progression and
      metastatic disease by facilitating the action of other signaling proteins. This
      accumulating body of evidence indicates that SFKs may represent a promising
      therapeutic target for the treatment of solid tumors. This review discusses the
      role of SFKs in solid tumors and the recent therapeutic advances aimed at
      targeting this family of tyrosine kinases in cancer.

PMID- 19581526
TI  - Personalizing cancer care: American Society of Clinical Oncology presidential
      address 2009.

PMID- 19581528
TI  - Effects of food on bioavailability of lapatinib: useful data, wrong conclusion.

PMID- 19581530
TI  - Smudge cells, serum albumin, and prognosis in B-cell chronic lymphocytic
      leukemia.

PMID- 19581532
TI  - Have we established a stereotactic body radiotherapy regimen for liver
      metastases?

PMID- 19581533
TI  - American Society of Clinical Oncology guidance statement: the cost of cancer
      care.
AB  - Advances in early detection, prevention, and treatment have resulted in
      consistently falling cancer death rates in the United States. In parallel with
      these advances have come significant increases in the cost of cancer care. It is
      well established that the cost of health care (including cancer care) in the
      United States is growing more rapidly than the overall economy. In part, this is
      a result of the prices and rapid uptake of new agents and other technologies,
      including advances in imaging and therapeutic radiology. Conventional
      understanding suggests that high prices may reflect the costs and risks
      associated with the development, production, and marketing of new drugs and
      technologies, many of which are valued highly by physicians, patients, and
      payers. The increasing cost of cancer care impacts many stakeholders who play a
      role in a complex health care system. Our patients are the most vulnerable
      because they often experience uneven insurance coverage, leading to financial
      strain or even ruin. Other key groups include pharmaceutical manufacturers that
      pass along research, development, and marketing costs to the consumer; providers
      of cancer care who dispense increasingly expensive drugs and technologies; and
      the insurance industry, which ultimately passes costs to consumers. Increasingly,
      the economic burden of health care in general, and high-quality cancer care in
      particular, will be less and less affordable for an increasing number of
      Americans unless steps are taken to curb current trends. The American Society of
      Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis,
      and treatment and eliminating disparities in cancer care through support of
      evidence-based and cost-effective practices. To address this goal, ASCO
      established a Cost of Care Task Force, which has developed this Guidance
      Statement on the Cost of Cancer Care. This Guidance Statement provides a concise
      overview of the economic issues facing stakeholders in the cancer community. It
      also recommends that the following steps be taken to address immediate needs:
      recognition that patient-physician discussions regarding the cost of care are an
      important component of high-quality care; the design of educational and support
      tools for oncology providers to promote effective communication about costs with
      patients; and the development of resources to help educate patients about the
      high cost of cancer care to help guide their decision making regarding treatment
      options. Looking to the future, this Guidance Statement also recommends that ASCO
      develop policy positions to address the underlying factors contributing to the
      increased cost of cancer care. Doing so will require a clear understanding of the
      factors that drive these costs, as well as potential modifications to the current
      cancer care system to ensure that all Americans have access to high-quality, cost
      effective care.

PMID- 19581534
TI  - Plasmablastic lymphoma in an immunocompetent patient.

PMID- 19581535
TI  - Late effects of conformal radiation therapy for pediatric patients with low-grade
      glioma: prospective evaluation of cognitive, endocrine, and hearing deficits.
AB  - PURPOSE: We conducted a prospective trial to evaluate late effects in pediatric
      patients with low-grade glioma (LGG) treated with conformal radiation therapy
      (CRT). PATIENTS AND METHODS: Between August 1997 and August 2006, 78 pediatric
      patients with LGG (mean age, 9.7 years; standard deviation, +/-4.4 years)
      received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations
      were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17).
      Baseline and serial evaluations were performed to identify deficits in cognition,
      endocrine function, and hearing. Deficits were correlated with clinical factors
      and radiation dose within specific normal tissue volumes. RESULTS: Cognitive
      effects of CRT through 5 years after CRT correlated with patient age,
      neurofibromatosis type 1 status, tumor location and volume, extent of resection,
      and radiation dose. The effect of age exceeded that of radiation dose; patients
      younger than 5 years experienced the greatest decline in cognition. Before CRT,
      growth hormone (GH) secretion abnormality was diagnosed in 24% of tested
      patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH
      replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid
      replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%.
      The mean +/- standard errors of the cumulative incidence of hearing loss at 10
      years did not exceed 5.7% +/- 3.3% at any frequency. CONCLUSION: To our
      knowledge, this is the largest series of prospectively followed children with LGG
      to undergo irradiation. Adverse effects are limited and predictable for most
      patients; however, this study provides additional evidence that CRT should be
      delayed for young patients and identifies the potential benefits of reducing
      radiation dose to normal brain.

PMID- 19581536
TI  - Phase II trial of conformal radiation therapy for pediatric low-grade glioma.
AB  - PURPOSE: The use of radiotherapy in pediatric low-grade glioma (LGG) is
      controversial, especially for young patients. We conducted a phase II trial of
      conformal radiation therapy (CRT) to estimate disease control by using a 10-mm
      clinical target volume (CTV) margin. MATERIALS AND METHODS: Between August 1997
      and August 2006, 78 pediatric patients with LGG and a median age of 8.9 years
      (range, 2.2 to 19.8 years) received 54 Gy CRT by using a 10-mm CTV and by
      targeting with systematic magnetic resonance imaging (MRI) registration. Tumor
      locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum
      (n = 17). Sixty-seven patients had documented or presumed WHO grade 1 tumors, 25
      patients had prior chemotherapy, and 13 patients had neurofibromatosis type 1.
      RESULTS: During a median follow-up of 89 months, 13 patients experienced disease
      progression. One patient experienced marginal treatment failure, eight
      experienced local failures, and four experienced metastatic failure. The mean and
      standard error 5- and 10-year event-free (87.4% +/- 4.4% and 74.3% +/- 15.4%,
      respectively) and overall (98.5% +/- 1.6% and 95.9% +/- 5.8%, respectively)
      survival rates were determined. The mean and standard error cumulative incidences
      of local failure at 5 and 10 years were 8.7% +/- 3.5% and 16.4% +/- 5.4%,
      respectively. The mean and standard error cumulative incidence of vasculopathy
      was 4.79% +/- 2.73% at 6 years, and it was higher for those younger than 5 years
      of age (P = .0105) at the time of CRT. CONCLUSION: This large, prospective series
      of irradiated children with LGG demonstrates that CRT with a 10-mm CTV does not
      compromise disease control. The results suggest that CRT should be delayed in
      young patients to reduce the risk of vasculopathy.

PMID- 19581537
TI  - Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine
      (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in
      patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative
      Oncology Group.
AB  - PURPOSE: Single-agent gemcitabine (GEM) is standard treatment of metastatic
      pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown
      promise in early clinical trials. E6201 was designed to compare overall survival
      (OS) of standard weekly GEM 1,000 mg/m(2)/30 minutes versus GEM FDR 1,500
      mg/m(2)/150 minutes or GEM 1,000 mg/m(2)/100 minutes/day 1 plus oxaliplatin 100
      mg/m(2)/day 2 every 14 days (GEMOX). METHODS: This trial included patients with
      metastatic or locally advanced pancreatic cancer, normal organ function, and
      performance status of 0 to 2. The study was designed to detect a 33% difference
      in median survival (hazard ratio [HR] < or = 0.75 for either of the experimental
      arms) with 81% power while maintaining a significance level of 2.5% in a two
      sided test for each of the two primary comparisons. RESULTS: Eight hundred thirty
      two patients were enrolled. The median survival and 1-year survival were 4.9
      months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and
      21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI,
      4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of
      these differences met the prespecified criteria for significance. Survival was
      9.2 months for patients with locally advanced disease, and 5.4 months for those
      with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest
      with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy.
      CONCLUSION: Neither GEM FDR nor GEMOX resulted in substantially improved survival
      or symptom benefit over standard GEM in patients with advanced pancreatic cancer.

PMID- 19581538
TI  - Patients with Merkel cell carcinoma tumors < or = 1.0 cm in diameter are unlikely
      to harbor regional lymph node metastasis.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine
      cutaneous malignancy. Current recommendations include offering regional lymph
      node evaluation by either sentinel lymph node biopsy (SLNB) or complete lymph
      node dissection (CLND) to all patients with MCC; however, we hypothesized a
      cohort of low-risk patients may exist for whom regional nodal metastasis would be
      unlikely. METHODS: A retrospective review of the Department of Veterans Affairs
      national health care database was performed. Patients undergoing resection of
      primary MCC were identified; and demographic, medical, and social history; tumor
      characteristics; nodal status; and recurrence events were recorded. RESULTS:
      Between 1995 and 2006, 346 patients were diagnosed with MCC. Of these, 213
      underwent resection of the primary lesion and evaluation of the draining lymph
      node basin. Fifty-four patients (25%) had tumors < or = 1.0 cm in diameter.
      Average tumor diameter was 0.7 cm, and 63% were located on the head or neck. Only
      two patients (4%) with tumors < or = 1.0 cm had regional lymph node metastasis,
      compared with 51 (24%) of 213 patients with tumors more than 1.0 cm (P < .0001).
      Both patients had clinically evident nodal disease at presentation and underwent
      CLND. Both have remained recurrence-free for 40 months. Thirteen (25%) of 51
      patients with nodal metastasis and tumors more than 1 cm had occult nodal
      metastasis. CONCLUSION: In this series, patients with MCC < or = 1.0 cm were
      unlikely to have regional lymph node metastasis, suggesting that regional nodal
      evaluation may reasonably be avoided in these patients. However, these data
      support SLNB for MCC more than 1 cm in diameter.

PMID- 19581539
TI  - Phase III study to evaluate temsirolimus compared with investigator's choice
      therapy for the treatment of relapsed or refractory mantle cell lymphoma.
AB  - PURPOSE: Temsirolimus, a specific inhibitor of the mammalian target of rapamycin
      kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated
      two dose regimens of temsirolimus in comparison with investigator's choice single
      agent therapy in relapsed or refractory disease. PATIENTS AND METHODS: In this
      multicenter, open-label, phase III study, 162 patients with relapsed or
      refractory MCL were randomly assigned (1:1:1) to receive one of two temsirolimus
      regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg
      (175/25-mg) weekly, or investigator's choice therapy from prospectively approved
      options. The primary end point was progression-free survival (PFS) by independent
      assessment. RESULTS: Median PFS was 4.8, 3.4, and 1.9 months for the temsirolimus
      175/75-mg, 175/25-mg, and investigator's choice groups, respectively. Patients
      treated with temsirolimus 175/75-mg had significantly longer PFS than those
      treated with investigator's choice therapy (P = .0009; hazard ratio = 0.44);
      those treated with temsirolimus 175/25-mg showed a trend toward longer PFS (P =
      .0618; hazard ratio = 0.65). Objective response rate was significantly higher in
      the 175/75-mg group (22%) compared with the investigator's choice group (2%; P =
      .0019). Median overall survival for the temsirolimus 175/75-mg group and the
      investigator's choice group was 12.8 months and 9.7 months, respectively (P =
      .3519). The most frequent grade 3 or 4 adverse events in the temsirolimus groups
      were thrombocytopenia, anemia, neutropenia, and asthenia. CONCLUSION:
      Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly
      improved PFS and objective response rate compared with investigator's choice
      therapy in patients with relapsed or refractory MCL.

PMID- 19581540
TI  - Myeloablative hematopoietic cell transplantation for acute lymphoblastic
      leukemia: analysis of graft sources and long-term outcome.
AB  - PURPOSE: Analysis of hematopoietic cell transplantation (HCT) for high-risk or
      recurrent acute lymphoblastic leukemia (ALL) using different donor sources is
      confounded by variable conditioning and supportive care. PATIENTS AND METHODS: We
      studied 623 consecutive ALL myeloablative HCT (1980 to 2005). Donors were
      autologous (n = 209), related (RD; n = 245), unrelated (URD; n = 100), and
      umbilical cord blood (UCB; n = 69). RESULTS: After median of 8.3 years of follow
      up, 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were
      29% (95% CI, 26% to 32%), 26% (95% CI, 23% to 29%), and 43% (95% CI, 39% to 47%),
      respectively. Treatment-related mortality (TRM) at 2 years was 28% (95% CI, 25%
      to 31%). Mismatched URD sources yielded higher TRM (relative risk [RR], 2.2; P <
      .01) and lower OS (RR, 1.5; P = .05) than RD or UCB HCT. Autografting yielded
      significantly more relapse (68%; 95% CI, 59% to 77%; P < .01) and poorer LFS
      (14%; 95% CI, 10% to 18%; P = .01). HCT in first complete remission (CR1) yielded
      significantly better outcomes than later HCT. In a 1990 to 2005 allogeneic
      CR1/second complete response cohort, 5-year OS, LFS, and relapse rates were 41%
      (95% CI, 35% to 47%), 38% (95% CI, 32% to 44%), and 25% (95% CI, 19% to 31%),
      respectively; 2-year TRM was 34% (95% CI, 28% to 40%). With RD, well-matched URD
      and UCB sources, 5-year LFS was 40% (95% CI, 31% to 49%), 42% (95% CI, 14% to
      70%), and 49% (95% CI, 34% to 64%), respectively, while relapse was 31% (95% CI,
      22% to 40%), 17% (95% CI, 0% to 37%), and 27% (95% CI, 13% to 41%). Acute graft
      versus-host disease was associated with fewer relapses. Since 1995, we noted
      progressive improvements in OS, LFS, and TRM. CONCLUSION: Allogeneic, but not
      autologous, HCT for ALL results in durable LFS. Importantly, HCT using UCB led to
      similar outcomes as either RD or well-matched URD. HCT in early remission can
      best exploit the potent antileukemic efficacy of allografting from UCB, RD, or
      URD sources.

PMID- 19581541
TI  - The legal drinking age and underage drinking in the United States.

PMID- 19581542
TI  - Xylitol pediatric topical oral syrup to prevent dental caries: a double-blind
      randomized clinical trial of efficacy.
AB  - OBJECTIVES: To evaluate the effectiveness of a xylitol pediatric topical oral
      syrup to reduce the incidence of dental caries among very young children and to
      evaluate the effect of xylitol in reducing acute otitis media in a subsequent
      study. DESIGN: Double-blind randomized controlled trial. SETTING: Communities in
      the Republic of the Marshall Islands. PARTICIPANTS: One hundred eight children
      aged 9 to 15 months were screened, and 100 were enrolled. Intervention Children
      were randomized to receive xylitol topical oral syrup (administered by their
      parents) twice a day (2 xylitol [4.00-g] doses and 1 sorbitol dose) (Xyl-2 x
      group) or thrice per day (3 xylitol [2.67-g] doses) (Xyl-3x group) vs a control
      syrup (1 xylitol [2.67-g] dose and 2 sorbitol doses) (control group). MAIN
      OUTCOME MEASURES: The primary outcome end point of the study was the number of
      decayed primary teeth. A secondary outcome end point was the incidence of acute
      otitis media for reporting in a subsequent report. RESULTS: Ninety-four children
      (mean [SD] age, 15.0 [2.7] months at randomization) with at least 1 follow-up
      examination were included in the intent-to-treat analysis. The mean (SD) follow
      up period was 10.5 (2.2) months. Fifteen of 29 of the children in the control
      group (51.7%) had tooth decay compared with 13 of 32 children in the Xyl-3x group
      (40.6%) and eight of 33 children in the Xyl-2x group (24.2%). The mean (SD)
      numbers of decayed teeth were 1.9 (2.4) in the control group, 1.0 (1.4) in the
      Xyl-3x group, and 0.6 (1.1) in the Xyl-2x group. Compared with the control group,
      there were significantly fewer decayed teeth in the Xyl-2x group (relative risk,
      0.30; 95% confidence interval, 0.13-0.66; P = .003) and in the Xyl-3x group
      (0.50; 0.26-0.96; P = .04). No statistical difference was noted between the 2
      xylitol treatment groups (P = .22). CONCLUSION: Xylitol oral syrup administered
      topically 2 or 3 times daily at a total daily dose of 8 g was effective in
      preventing early childhood caries.

PMID- 19581543
TI  - Neighborhood income and health outcomes in infants: how do those with complex
      chronic conditions fare?
AB  - OBJECTIVE: To quantify the effect of socioeconomic status (SES) on health
      outcomes during the first year after newborn discharge among infants with complex
      chronic conditions (CCCs) insured through a universal health plan. DESIGN:
      Longitudinal, population-based cohort study. SETTING: Ontario, Canada.
      PARTICIPANTS: Infants born in hospitals from April 1, 1996, through March 31,
      2000. Infants with CCCs were identified from their newborn discharge records.
      Neighborhood income quintiles were obtained by linking participants' postal codes
      to census data. MAIN OUTCOME MEASURES: Mortality and hospital admissions in the
      first year after newborn discharge. Logistic and Poisson regression analyses were
      used to examine the relationship between neighborhood income quintiles and
      outcomes, adjusting for important covariates such as low birth weight and rural
      residence. RESULTS: A total of 512 768 infants were included, of whom 2.3% had
      CCCs at newborn discharge. Infants with CCCs accounted for 37.8% of deaths and
      11.0% of hospitalizations during the first year after the newborn discharge.
      Infants with CCCs living in the lowest-income neighborhoods had a 1.26-fold
      higher mortality risk (95% confidence interval, 0.83-1.90; P = .28) and a 1.24
      fold higher hospitalization rate (1.09-1.40; P < .001) compared with those living
      in the highest-income neighborhoods. Although the income gradients associated
      with mortality and hospitalization were less pronounced among infants with CCCs
      compared with infants without CCCs, the absolute interquintile risk differences
      attributable to SES were higher among infants with CCCs. CONCLUSIONS: Despite
      universal health insurance, SES-related inequality affects hospitalization and,
      possibly, mortality rates among medically vulnerable infants.

PMID- 19581544
TI  - Maternal-fetal disproportion and birth asphyxia in rural Sarlahi, Nepal.
AB  - OBJECTIVE: To assess the risk of birth asphyxia associated with maternal and
      newborn size. DESIGN: Cohort study. SETTING: Rural community in the Sarlahi
      district of Nepal. PARTICIPANTS: Mothers and newborns (n = 3189). OUTCOME
      MEASURE: Birth asphyxia, defined as an infant who failed to cry at birth, and who
      was unable to breathe or suckle normally after birth or had convulsions. RESULTS:
      Birth asphyxia occurred in 78 of 1000 live births, and asphyxia-specific
      mortality was 11 per 1000 live births. After controlling for confounding factors,
      mothers with height shorter than 145 cm were more likely to have an infant with
      birth asphyxia compared with mothers 145 cm or taller (adjusted relative risk
      [RR], 1.5; 95% confidence interval [CI], 1.1-2.0). Mothers with mid-upper arm
      circumference smaller than 21.5 cm carried a higher risk of delivering an infant
      with birth asphyxia compared with those with arm circumference greater than 23 cm
      (adjusted RR, 1.5; 95% CI, 1.1- 2.0). Asphyxia was more common among newborns
      with head circumference greater than 33.5 cm than those with head circumferences
      32.6 to 33.5 cm (adjusted RR, 1.6; 95% CI, 1.1-2.2). Birth weight was not
      independently associated with birth asphyxia; however, there was significant
      interaction between maternal stature and birth weight (P = .01); a 3300-g infant
      born to a mother shorter than 145 cm carried a 3.8 times higher asphyxia risk
      (95% CI, 2.2-6.5) than an infant of median weight (2620 g) born to a mother
      taller than 145 cm. CONCLUSIONS: In rural Nepal, maternal stunting and wasting
      and large infant head circumference carried higher risk of neonatal asphyxia.
      Maternal-fetal disproportion resulted in a synergistic elevation in asphyxia
      risk.

PMID- 19581545
TI  - Project ALERT: a cluster randomized trial.
AB  - OBJECTIVE: To evaluate the effects of Project ALERT on adolescents' lifetime and
      30-day use of cigarettes, alcohol, marijuana, and inhalants. DESIGN: Cluster
      randomized trial. SETTING: Schools from 11 states were enrolled in 2 successive
      cohorts from 2004 to 2008. PARTICIPANTS: All public schools in the United States
      that included grades 6 through 8 and enrolled at least 100 students in sixth
      grade were recruited. Of the 40 schools that began the study, 34 (17 per
      condition) completed it. Data were analyzed from 5883 unique participants.
      Intervention Project ALERT, a manualized classroom-based substance use prevention
      curriculum for the middle grades, was taught to sixth and seventh graders. MAIN
      OUTCOME MEASURES: Students were surveyed before the onset of the intervention, as
      sixth graders, and after the completion of the 2-year intervention, as seventh
      graders. Outcome measures included lifetime and 30-day use of cigarettes,
      alcohol, marijuana, and inhalants. RESULTS: At baseline, students in the
      intervention condition were slightly to moderately more likely to report use for
      each of the 8 measures examined than were students in the control condition. For
      all measures except lifetime use of cigarettes, these differences were less
      pronounced at follow-up and therefore were in the direction of favorable program
      effects. These changes were statistically significant, however, for only 1
      outcome measure, past 30-day use of alcohol (reduction in the adjusted odds ratio
      from 2.07 at baseline to 1.32 at follow-up; P = .006). CONCLUSION: Project ALERT
      was not effective when delivered to the sixth grade population we targeted.

PMID- 19581546
TI  - Tipping the balance: use of advergames to promote consumption of nutritious foods
      and beverages by low-income African American children.
AB  - OBJECTIVE: To examine how advergames, which are online computer games developed
      to market a product, affect consumption of healthier and less healthy snacks by
      low-income African American children. DESIGN: Cross-sectional, between-subjects
      examination of an advergame in which children were rewarded for having their
      computer character consume healthier or less healthy foods and beverages.
      Children were randomly assigned to 1 of the following 3 conditions: (1) the
      healthier advergame condition, (2) the less healthy advergame condition, or (3)
      the control condition. SETTING: Urban public elementary schools. PARTICIPANTS:
      Thirty low-income, African American children aged 9 to 10 years. Main Exposure
      Children in the treatment conditions played a less healthy or a healthier version
      of an advergame 2 times before choosing and eating a snack and completing the
      experimental measures. Children in the control group chose and ate a snack before
      playing the game and completing the measures. MAIN OUTCOME MEASURES: The number
      of healthier snack items children selected and ate and how much children liked
      the game. RESULTS: Children who played the healthier version of the advergame
      selected and ate significantly more healthy snacks than did those who played the
      less healthy version. Children reported liking the advergame. CONCLUSIONS:
      Findings suggest that concerns about online advergames that market unhealthy
      foods are justified. However, advergames may also be used to promote healthier
      foods and beverages. This kind of social marketing approach could tip the scales
      toward the selection of higher-quality snacks, thereby helping to curb the
      obesity epidemic.

PMID- 19581547
TI  - Influence of movie smoking exposure and team sports participation on established
      smoking.
AB  - OBJECTIVE: To examine the joint effects of movie smoking exposure and team sports
      participation on established smoking. DESIGN: Longitudinal study. SETTING: School
      and telephone-based surveys in New Hampshire and Vermont between September 1999
      through November 1999 and February 2006 through February 2007. PARTICIPANTS: A
      total of 2048 youths aged 16 to 21 years at follow-up. Main Exposures Baseline
      movie smoking exposure categorized in quartiles assessed when respondents were
      aged 9 to 14 years and team sports participation assessed when respondents were
      aged 16 to 21 years. Main Outcome Measure Established smoking (having smoked > or
      =100 cigarettes in one's lifetime) at follow-up. RESULTS: At follow-up, 353
      respondents (17.2%) were established smokers. Exposure to the highest quartile of
      movie smoking compared with the lowest increased the likelihood of established
      smoking (odds ratio = 1.63; 95% confidence interval, 1.03-2.57), and team sports
      nonparticipants compared with participants were twice as likely to be established
      smokers (odds ratio = 2.01; 95% confidence interval, 1.47-2.74). The joint
      effects of movie smoking exposure and team sports participation revealed that at
      each quartile of movie smoking exposure, the odds of established smoking were
      greater for team sports nonparticipants than for participants. We saw a dose
      response relationship of movie smoking exposure for established smoking only
      among team sports participants. CONCLUSIONS: Team sports participation clearly
      plays a protective role against established smoking, even in the face of exposure
      to movie smoking. However, movie smoking exposure increases the risk of
      established smoking among both team sports participants and nonparticipants.
      Parents, teachers, coaches, and clinicians should be aware that encouraging team
      sports participation in tandem with minimizing early exposure to movie smoking
      may offer the greatest likelihood of preventing youth smoking.

PMID- 19581549
TI  - Until the last breath: exploring the concept of hope for parents and health care
      professionals during a child's serious illness.
AB  - OBJECTIVE: To investigate the concept of hope for families and pediatric health
      care professionals during a child's serious illness. DESIGN: Eight focus groups.
      SETTING: Academic pediatric medical center. PARTICIPANTS: Bereaved parents,
      pediatricians, pediatric residents, and nurses (N = 39). Intervention
      Participants were asked standardized questions related to their definition of
      hope, its role in medical decisions, and the benefits and detriments of hope in
      focus group sessions. MAIN OUTCOME MEASURES: We identified attributes of
      participants' concepts of hope using qualitative analysis of audio-taped
      sessions. RESULTS: While all participants identified common elements in their
      definition of hope, parents identified their role as bearers of hope; it was a
      cornerstone of decision making. Health care professionals tended to view hope as
      related to a positive outcome. Some physicians reported difficulty in maintaining
      hope in the face of prognostic data; others acknowledged the importance of the
      family's hope. Nurses identified particular challenges around parents' decisions
      to continue treatment when it prolonged the child's suffering. All participants
      noted the changing nature of hope and its implications for care. CONCLUSIONS: The
      tension between maintaining hope and accepting the reality of the prognosis may
      lessen when acknowledging that parents see their role as bearers of hope.
      Supporting families around the changing nature of hope may allow health care
      professionals to partner with parents while maintaining honest communication.

PMID- 19581548
TI  - Depression, sexually transmitted infection, and sexual risk behavior among young
      adults in the United States.
AB  - OBJECTIVE: To measure associations among depression, sexual risk behaviors, and
      sexually transmitted infection (STI) among white and black youth in the United
      States. DESIGN: Analysis of prospective cohort study data. Wave I of the National
      Longitudinal Study of Adolescent Health occurred in 1995 when participants were
      in grades 7 through 12. Six years later, all Wave I participants who could be
      located were invited to participate in Wave III and to provide a urine specimen
      for STI testing. SETTING: In-home interviews in the continental United States,
      Alaska, and Hawaii. PARTICIPANTS: Population-based sample. A total of 10 783 Wave
      I (adolescence) and Wave III (adulthood) white and black respondents with sample
      weight variables. Main Exposures Chronic depression (detected at Waves I and III)
      and recent depression (detected at Wave III only) vs no adult depression (not
      detected at Wave III). OUTCOME MEASURES: Multiple sexual partners and
      inconsistent condom use in the past year and a current positive test result for
      Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis
      (adulthood). RESULTS: Recent or chronic depression in adulthood was more common
      for blacks (women, 19.3%; men, 11.9%) than for whites (women, 13.0%; men, 8.1%).
      Among all groups (white men and women, and black men and women), adult depression
      was associated with multiple partners but not with condom use. Among black men,
      depression was strongly associated with STI (recent: adjusted prevalence ratio,
      2.36; 95% confidence interval, 1.26-4.43; chronic: adjusted prevalence ratio,
      3.05; 95% confidence interval, 1.48-6.28); having multiple partners did not
      mediate associations between depression and STI. CONCLUSIONS: Integration of
      mental health and STI programs for youth is warranted. Further research is needed
      to elucidate how depression may influence the prevalence of STI among black men.

PMID- 19581550
TI  - Variations between hospitals in antireflux procedures in children.
AB  - OBJECTIVE: To examine the differences and trends in pediatric antireflux
      procedures (ARPs) across individual pediatric hospitals over time. DESIGN:
      Retrospective cohort study. SETTING: Administrative database containing inpatient
      records with discharge dates between January 1, 2001, and March 31, 2006.
      PARTICIPANTS: Hospitalized pediatric patients younger than 18 years with primary
      procedure codes for ARP, appendectomy, pyloromyotomy, and gastrostomy tube
      placement. The comparisons with admissions for these common procedures were used
      to identify changes in the incidence of ARP per hospital per year. MAIN OUTCOME
      MEASURES: The ratio of ARPs to appendectomies, pyloromyotomies, gastrostomies,
      and all 3 procedures combined, in each hospital by year. RESULTS: During our
      study period 13 691 ARPs, 41 441 nonincidental appendectomies, 14 895
      pyloromyotomies, and 23 527 gastrostomy tube placements were identified. The
      average number of ARPs per appendectomy, pyloromyotomy, and gastrostomy tube
      placement declined annually across free-standing pediatric institutions. When
      these annual changes are examined within each hospital individually, however, it
      appears that such changes are not occurring equally, in that some hospitals are
      performing significantly greater and some significantly fewer ARPs relative to
      these common procedures. CONCLUSIONS: The number of ARPs being performed in 36
      free-standing children's hospitals is decreasing each year relative to several
      operations commonly performed at these institutions. Despite this overall annual
      decrease, there is tremendous variation between individual hospitals in how
      frequently ARPs are being performed relative to these procedures.

PMID- 19581551
TI  - Picture of the month--quiz case. Klippel-Trenaunay syndrome.

PMID- 19581553
TI  - Solving the problem of early childhood caries: a challenge for us all.

PMID- 19581554
TI  - Poorer health: the persistent and protean connections between poverty, social
      inequality, and child well-being.

PMID- 19581555
TI  - Addressing maternal nutrition and risks of birth asphyxia in developing
      countries.

PMID- 19581557
TI  - Universal primer polymerase chain reaction looks promising for newborns with low
      pretest probability of sepsis.

PMID- 19581556
TI  - Fructose and oxidized low-density lipoprotein in pediatric nonalcoholic fatty
      liver disease: a pilot study.

PMID- 19581558
TI  - Advice for patients. Nutrition and media literacy.

PMID- 19581559
TI  - Into the World There Came a Soul Called Ida.

PMID- 19581560
TI  - Efficacy of an Internet-based behavioral intervention for adults with insomnia.
AB  - CONTEXT: Insomnia is a major health problem with significant psychological,
      health, and economic consequences. However, availability of one of the most
      effective insomnia treatments, cognitive behavioral therapy, is significantly
      limited. The Internet may be a key conduit for delivering this intervention.
      OBJECTIVE: To evaluate the efficacy of a structured behavioral Internet
      intervention for adults with insomnia. DESIGN, SETTING, AND PARTICIPANTS: Forty
      five adults were randomly assigned to an Internet intervention (n = 22) or wait
      list control group (n = 23). Forty-four eligible participants (mean [SD] age,
      44.86 [11.03] years; 34 women) who had a history of sleep difficulties longer
      than 10 years on average (mean [SD], 10.59 [8.89] years) were included in the
      analyses. INTERVENTION: The Internet intervention is based on well-established
      face-to-face cognitive behavioral therapy incorporating the primary components of
      sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and
      relapse prevention. MAIN OUTCOME MEASURES: The Insomnia Severity Index and daily
      sleep diary data were used to determine changes in insomnia severity and the main
      sleep variables, including wake after sleep onset and sleep efficiency. RESULTS:
      Intention-to-treat analyses showed that scores on the Insomnia Severity Index
      significantly improved from 15.73 (95% confidence interval [CI], 14.07 to 17.39)
      to 6.59 (95% CI, 4.73 to 8.45) for the Internet group but did not change for the
      control group (16.27 [95% CI, 14.61 to 17.94] to 15.50 [95% CI, 13.64 to 17.36])
      (F(1,42) = 29.64; P < .001). The Internet group maintained their gains at the 6
      month follow-up. Internet participants also achieved significant decreases in
      wake after sleep onset (55% [95% CI, 34% to 76%]) and increases in sleep
      efficiency (16% [95% CI, 9% to 22%]) compared with the nonsignificant control
      group changes of wake after sleep onset (8% [95% CI, -17% to 33%) and sleep
      efficiency (3%; 95% CI, -4% to 9%). CONCLUSIONS: Participants who received the
      Internet intervention for insomnia significantly improved their sleep, whereas
      the control group did not have a significant change. The Internet appears to have
      considerable potential in delivering a structured behavioral program for
      insomnia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00328250.

PMID- 19581562
TI  - Somatic hospital contacts, invasive cardiac procedures, and mortality from heart
      disease in patients with severe mental disorder.
AB  - CONTEXT: Excess mortality from heart disease is observed in patients with severe
      mental disorder. This excess mortality may be rooted in adverse effects of
      pharmacological or psychotropic treatment, lifestyle factors, or inadequate
      somatic care. OBJECTIVES: To examine whether persons with severe mental disorder,
      defined as persons admitted to a psychiatric hospital with bipolar affective
      disorder, schizoaffective disorder, or schizophrenia, are in contact with
      hospitals and undergoing invasive procedures for heart disease to the same degree
      as the nonpsychiatric general population, and to determine whether they have
      higher mortality rates of heart disease. DESIGN, SETTING, AND PARTICIPANTS: A
      population-based cohort of 4.6 million persons born in Denmark was followed up
      from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures
      were estimated by survival analysis. MAIN OUTCOME MEASURES: Incidence rate ratios
      of heart disease admissions and heart disease mortality as well as probability of
      invasive cardiac procedures. RESULTS: The incidence rate ratio of heart disease
      contacts in persons with severe mental disorder compared with the rate for the
      nonpsychiatric general population was only slightly increased, at 1.11 (95%
      confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio
      from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years
      after the first contact for somatic heart disease, the risk of dying of heart
      disease was 8.26% for persons with severe mental disorder (aged <70 years) but
      only 2.86% in patients with heart disease who had never been admitted to a
      psychiatric hospital. The fraction undergoing invasive procedures within 5 years
      was reduced among patients with severe mental disorder as compared with the
      nonpsychiatric general population (7.04% vs 12.27%, respectively). CONCLUSIONS:
      Individuals with severe mental disorder had only negligible excess rates of
      contact for heart disease. Given their excess mortality from heart disease and
      lower rates of invasive procedures after first contact, it would seem that the
      treatment for heart disease offered to these individuals in Denmark is neither
      sufficiently efficient nor sufficiently intensive. This undertreatment may
      explain part of their excess mortality.

PMID- 19581561
TI  - Use of neuroanatomical pattern classification to identify subjects in at-risk
      mental states of psychosis and predict disease transition.
AB  - CONTEXT: Identification of individuals at high risk of developing psychosis has
      relied on prodromal symptomatology. Recently, machine learning algorithms have
      been successfully used for magnetic resonance imaging-based diagnostic
      classification of neuropsychiatric patient populations. OBJECTIVE: To determine
      whether multivariate neuroanatomical pattern classification facilitates
      identification of individuals in different at-risk mental states (ARMS) of
      psychosis and enables the prediction of disease transition at the individual
      level. DESIGN: Multivariate neuroanatomical pattern classification was performed
      on the structural magnetic resonance imaging data of individuals in early or late
      ARMS vs healthy controls (HCs). The predictive power of the method was then
      evaluated by categorizing the baseline imaging data of individuals with
      transition to psychosis vs those without transition vs HCs after 4 years of
      clinical follow-up. Classification generalizability was estimated by cross
      validation and by categorizing an independent cohort of 45 new HCs. SETTING:
      Departments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University,
      Munich, Germany. PARTICIPANTS: The first classification analysis included 20
      early and 25 late at-risk individuals and 25 matched HCs. The second analysis
      consisted of 15 individuals with transition, 18 without transition, and 17
      matched HCs. MAIN OUTCOME MEASURES: Specificity, sensitivity, and accuracy of
      classification. RESULTS: The 3-group, cross-validated classification accuracies
      of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals
      vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in
      the second analysis were 90% (HCs vs the rest), 88% (individuals with transition
      vs the rest), and 86% (individuals without transition vs the rest). Independent
      HCs were correctly classified in 96% (first analysis) and 93% (second analysis)
      of cases. CONCLUSIONS: Different ARMSs and their clinical outcomes may be
      reliably identified on an individual basis by assessing patterns of whole-brain
      neuroanatomical abnormalities. These patterns may serve as valuable biomarkers
      for the clinician to guide early detection in the prodromal phase of psychosis.

PMID- 19581563
TI  - Association of GSK3beta polymorphisms with brain structural changes in major
      depressive disorder.
AB  - CONTEXT: Indirect evidence suggests that the glycogen synthase kinase-3beta
      (GSK3beta) gene might be implicated in major depressive disorder (MDD).
      BACKGROUND: We evaluated 15 GSK3beta single-nucleotide polymorphisms (SNPs) to
      test for associations with regional gray matter (GM) volume differences in
      patients with recurrent MDD. We then used the defined regions of interest based
      on significant associations to test for MDD x genotype interactions by including
      a matched control group without any psychiatric disorder, including MDD. DESIGN:
      General linear model with nonstationary cluster-based inference. SETTING: Munich,
      Germany. PARTICIPANTS: Patients with recurrent MDD (n = 134) and age-, sex-, and
      ethnicity-matched healthy controls (n = 143). MAIN OUTCOME MEASURES: Associations
      between GSK3beta polymorphisms and regional GM volume differences. RESULTS:
      Variation in GM volume was associated with GSK3beta polymorphisms; the most
      significant associations were found for rs6438552, a putative functional intronic
      SNP that showed 3 significant GM clusters in the right and left superior temporal
      gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively,
      corrected for multiple comparisons across the whole brain). Similar results were
      obtained with rs12630592, an SNP in high linkage disequilibrium. A significant
      SNP x MDD status interaction was observed for the effect on GM volumes in the
      right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected,
      respectively). CONCLUSIONS: The GSK3beta gene may have a role in determining
      regional GM volume differences of the right hippocampus and bilateral superior
      temporal gyri. The association between genotype and brain structure was specific
      to the patients with MDD, suggesting that GSK3beta genotypes might interact with
      MDD status. We speculate that this is a consequence of regional neocortical,
      glial, or neuronal growth or survival. In considering core cognitive features of
      MDD, the association of GSK3beta polymorphisms with structural variation in the
      temporal lobe and hippocampus is of particular interest in the context of other
      evidence for structural and functional abnormalities in the hippocampi of
      patients with MDD.

PMID- 19581564
TI  - Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes:
      short-term efficacy and adverse effects.
AB  - CONTEXT: Medication resistance is the leading indication for use of
      electroconvulsive therapy (ECT) in major depression. The practice of stopping
      antidepressant medications prior to ECT derived from studies in the 1960s and
      1970s in nonresistant samples. There is also continuing controversy regarding the
      relative efficacy and adverse effects of right unilateral and bilateral ECT.
      OBJECTIVE: To test the hypotheses that, compared with placebo, concomitant
      treatment with nortriptline or venlafaxine during the ECT course enhances short
      term efficacy without a meaningful effect on adverse effects and reduces the rate
      of post-ECT relapse, and to test the hypotheses that high-dose, right-sided,
      unilateral ECT is equivalent in efficacy to moderate-dosage bilateral ECT and
      retains advantages with respect to cognitive adverse effects. DESIGN:
      Prospective, randomized, triple-masked, placebo-controlled study conducted from
      2001 through 2005. SETTING: Three university-based hospitals. PATIENTS: Of
      approximately 750 consecutive patients referred for ECT, 319 with a major
      depressive episode consented, were randomized to pharmacological or ECT treatment
      conditions, and received at least 1 ECT treatment. MAIN OUTCOME MEASURES: Scores
      on the Hamilton Rating Scale for Depression, remission rate following completion
      of ECT, and selective measures of cognitive adverse effects. RESULTS: Treatment
      with nortriptyline enhanced the efficacy and reduced the cognitive adverse
      effects of ECT relative to placebo. Venlafaxine resulted in a weaker degree of
      improvement and tended to worsen cognitive adverse effects. High-dosage right
      unilateral ECT did not differ or was superior to bilateral ECT in efficacy and
      resulted in less severe amnesia. CONCLUSIONS: The efficacy of ECT is
      substantially increased by the addition of an antidepressant medication, but such
      medications may differ in whether they reduce or increase cognitive adverse
      effects. High-dose, right-sided, unilateral ECT is at least equivalent to
      moderate-dosage bilateral ECT in efficacy, but retains advantages with respect to
      cognitive adverse effects.

PMID- 19581566
TI  - Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar
      disorder.
AB  - CONTEXT: Several data sources suggest a link between schizophrenia and bipolar
      disorder (BD); however, family studies have not revealed coaggregation of these
      disorders. OBJECTIVES: To systematically review family studies of probands with
      schizophrenia and BD and to determine whether these disorders coaggregate in
      families. DATA SOURCES: MEDLINE and PsycINFO databases. STUDY SELECTION: All
      family studies published from January 1, 1980, to December 31, 2006, reporting
      morbid risk or raw counts of schizophrenia or BD in first-degree relatives (FDRs)
      of a proband group with DSM-III or later; International Classification of
      Diseases, Ninth or Tenth Revision; or research diagnostic criteria schizophrenia
      or BD were included. Of the original 2326 studies identified through the database
      search, 38 studies were used to investigate rates of BD in FDRs of probands with
      schizophrenia, while 39 studies were used to examine rates of schizophrenia in
      FDRs of BD probands. DATA EXTRACTION: Data were analyzed with a novel random
      effects bootstrapping technique that allows for the inclusion of studies lacking
      a patient or control group, which made up a substantial portion of the available
      data. Data were also blindly weighted for methodological quality. DATA SYNTHESIS:
      The FDRs of probands with schizophrenia showed significantly (P = .01) increased
      rates of BD relative to control FDRs (odds ratio [OR] = 2.08). The FDRs of
      probands with BD showed marginally (P = .06) increased rates of schizophrenia
      relative to control FDRs (OR = 2.10); this analysis was significant (P = .02)
      when studies that did not report morbid risk estimates were excluded (in this
      case, OR = 3.49). CONCLUSIONS: This meta-analysis provides direct evidence for
      familial coaggregation of schizophrenia and BD, a finding that argues against the
      view that these disorders are entirely discrete diagnostic entities. Rather, a
      continuum model is supported.

PMID- 19581565
TI  - Predictive value of family history on severity of illness: the case for
      depression, anxiety, alcohol dependence, and drug dependence.
AB  - CONTEXT: If family history is associated with clinical features that are thought
      to index seriousness of disorder, this could inform clinicians predicting
      patients' prognosis and researchers selecting cases for genetic studies. Although
      tests of associations between family history and clinical features are numerous
      for depression, such tests are relatively lacking for other disorders. OBJECTIVE:
      To test the hypothesis that family history is associated with 4 clinical indexes
      of disorder (recurrence, impairment, service use, and age at onset) in relation
      to 4 psychiatric disorders (major depressive episode, anxiety disorder, alcohol
      dependence, and drug dependence). DESIGN: Prospective longitudinal cohort study.
      SETTING: New Zealand. PARTICIPANTS: A total of 981 members of the 1972 to 1973
      Dunedin Study birth cohort (96% retention). MAIN OUTCOME MEASURES: For each
      disorder, family history scores were calculated as the proportion of affected
      family members from data on 3 generations of the participants' families. Data
      collected prospectively at the study's repeated assessments (ages 11-32 years)
      were used to assess recurrence, impairment, and age at onset; data collected by
      means of a life history calendar at age 32 years were used to assess service use.
      RESULTS: Family history was associated with the presence of all 4 disorder types.
      In addition, family history was associated with a more recurrent course for all 4
      disorders (but not significantly for women with depression), worse impairment,
      and greater service use. Family history was not associated with younger age at
      onset for any disorder. CONCLUSIONS: Associations between family history of a
      disorder and clinical features of that disorder in probands showed consistent
      direction of effects across depression, anxiety disorder, alcohol dependence, and
      drug dependence. For these disorder types, family history is useful for
      determining patients' clinical prognosis and for selecting cases for genetic
      studies.

PMID- 19581567
TI  - N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a
      double-blind, placebo-controlled study.
AB  - CONTEXT: Trichotillomania is characterized by repetitive hair pulling that causes
      noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are
      limited to conflicting studies of serotonergic medications. N-acetylcysteine, an
      amino acid, seems to restore the extracellular glutamate concentration in the
      nucleus accumbens and, therefore, offers promise in the reduction of compulsive
      behavior. OBJECTIVE: To determine the efficacy and tolerability of N
      acetylcysteine in adults with trichotillomania. DESIGN: Twelve-week, double
      blind, placebo-controlled trial. SETTING: Ambulatory care center. PATIENTS: Fifty
      individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1]
      years). INTERVENTIONS: N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo
      was administered for 12 weeks. MAIN OUTCOME MEASURES: Patients were assessed
      using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global
      Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures
      of depression, anxiety, and psychosocial functioning. Outcomes were examined
      using analysis of variance modeling analyses and linear regression in an
      intention-to-treat population. RESULTS: Patients assigned to receive N
      acetylcysteine had significantly greater reductions in hair-pulling symptoms as
      measured using the Massachusetts General Hospital Hair Pulling Scale (P < .001)
      and the Psychiatric Institute Trichotillomania Scale (P = .001). Fifty-six
      percent of patients "much or very much improved" with N-acetylcysteine use
      compared with 16% taking placebo (P = .003). Significant improvement was
      initially noted after 9 weeks of treatment. CONCLUSIONS: This study, the first to
      our knowledge that examines the efficacy of a glutamatergic agent in the
      treatment of trichotillomania, found that N-acetylcysteine demonstrated
      statistically significant reductions in trichotillomania symptoms. No adverse
      events occurred in the N-acetylcysteine group, and N-acetylcysteine was well
      tolerated. Pharmacologic modulation of the glutamate system may prove to be
      useful in the control of a range of compulsive behaviors. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00354770.

PMID- 19581568
TI  - Childhood and adolescent psychiatric disorders as predictors of young adult
      disorders.
AB  - CONTEXT: Most adults with a psychiatric disorder first met diagnostic criteria
      during childhood and/or adolescence, yet specific homotypic and heterotypic
      patterns of prediction have not been firmly established. OBJECTIVE: To establish
      which childhood and adolescent psychiatric disorders predict particular young
      adult disorders when accounting for comorbidities, disaggregating similar
      disorders, and examining childhood and adolescent predictors separately. DESIGN:
      Eleven waves of data from the prospective population-based Great Smoky Mountains
      Study (N = 1420) were used. SETTING: The Great Smoky Mountains Study is a
      longitudinal study of the development of psychiatric disorder and need for mental
      health services in rural and urban youth. A representative sample of children was
      recruited from 11 counties in western North Carolina. PARTICIPANTS: Children in
      the community aged 9 to 16, 19, and 21 years. MAIN OUTCOME MEASURES: Common
      psychiatric disorders were assessed in childhood (ages 9-12 years) and
      adolescence (ages 13-16 years) with the Child and Adolescent Psychiatric
      Assessment and in young adulthood (ages 19 and 21 years) with the Young Adult
      Psychiatric Assessment. RESULTS: Adolescent depression significantly predicted
      young adult depression in the bivariate analysis, but this effect was entirely
      accounted for by comorbidity of adolescent depression with adolescent
      oppositional defiant disorder, anxiety, and substance disorders in adjusted
      analyses. Generalized anxiety and depression cross-predicted each other, and
      oppositional defiant disorder (but not conduct disorder) predicted later anxiety
      disorders and depression. Evidence of homotypic prediction was supported for
      substance use disorders, antisocial personality disorder (from conduct disorder),
      and anxiety disorders, although this effect was primarily accounted for by DSM
      III-R overanxious disorder. CONCLUSIONS: Stringent tests of homotypic and
      heterotypic prediction patterns suggest a more developmentally and diagnostically
      nuanced picture in comparison with the previous literature. The putative link
      between adolescent and young adult depression was not supported. Oppositional
      defiant disorder was singular in being part of the developmental history of a
      wide range of young adult disorders.

PMID- 19581571
TI  - Questionable efficacy for naltrexone in patients with Asp40.

PMID- 19581569
TI  - Genome-wide association study of alcohol dependence.
AB  - CONTEXT: Alcohol dependence is a serious and common public health problem. It is
      well established that genetic factors play a major role in the development of
      this disorder. Identification of genes that contribute to alcohol dependence will
      improve our understanding of the mechanisms that underlie this disorder.
      OBJECTIVE: To identify susceptibility genes for alcohol dependence through a
      genome-wide association study (GWAS) and a follow-up study in a population of
      German male inpatients with an early age at onset. DESIGN: The GWAS tested
      524,396 single-nucleotide polymorphisms (SNPs). All SNPs with P < 10(-4) were
      subjected to the follow-up study. In addition, nominally significant SNPs from
      genes that had also shown expression changes in rat brains after long-term
      alcohol consumption were selected for the follow-up step. SETTING: Five
      university hospitals in southern and central Germany. PARTICIPANTS: The GWAS
      included 487 male inpatients with alcohol dependence as defined by the DSM-IV and
      an age at onset younger than 28 years and 1358 population-based control
      individuals. The follow-up study included 1024 male inpatients and 996 age
      matched male controls. All the participants were of German descent. MAIN OUTCOME
      MEASURES: Significant association findings in the GWAS and follow-up study with
      the same alleles. RESULTS: The GWAS produced 121 SNPs with nominal P < 10(-4).
      These, together with 19 additional SNPs from homologues of rat genes showing
      differential expression, were genotyped in the follow-up sample. Fifteen SNPs
      showed significant association with the same allele as in the GWAS. In the
      combined analysis, 2 closely linked intergenic SNPs met genome-wide significance
      (rs7590720, P = 9.72 x 10(-9); rs1344694, P = 1.69 x 10(-8)). They are located on
      chromosome region 2q35, which has been implicated in linkage studies for alcohol
      phenotypes. Nine SNPs were located in genes, including the CDH13 and ADH1C genes,
      that have been reported to be associated with alcohol dependence. CONCLUSIONS:
      This is the first GWAS and follow-up study to identify a genome-wide significant
      association in alcohol dependence. Further independent studies are required to
      confirm these findings.

PMID- 19581570
TI  - Cross-national associations between gender and mental disorders in the World
      Health Organization World Mental Health Surveys.
AB  - CONTEXT: Gender differences in mental disorders, including more anxiety and mood
      disorders among women and more externalizing disorders among men, are found
      consistently in epidemiological surveys. The gender roles hypothesis suggests
      that these differences narrow as the roles of women and men become more equal.
      OBJECTIVES: To study time-space (cohort-country) variation in gender differences
      in lifetime DSM-IV mental disorders across cohorts in 15 countries in the World
      Health Organization World Mental Health Survey Initiative and to determine if
      this variation is significantly related to time-space variation in female gender
      role traditionality as measured by aggregate patterns of female education,
      employment, marital timing, and use of birth control. DESIGN: Face-to-face
      household surveys. SETTING: Africa, the Americas, Asia, Europe, the Middle East,
      and the Pacific. PARTICIPANTS: Community-dwelling adults (N = 72,933). MAIN
      OUTCOME MEASURES: The World Health Organization Composite International
      Diagnostic Interview assessed lifetime prevalence and age at onset of 18 DSM-IV
      anxiety, mood, externalizing, and substance disorders. Survival analyses
      estimated time-space variation in female to male odds ratios of these disorders
      across cohorts defined by the following age ranges: 18 to 34, 35 to 49, 50 to 64,
      and 65 years and older. Structural equation analysis examined predictive effects
      of variation in gender role traditionality on these odds ratios. RESULTS: In all
      cohorts and countries, women had more anxiety and mood disorders than men, and
      men had more externalizing and substance disorders than women. Although gender
      differences were generally consistent across cohorts, significant narrowing was
      found in recent cohorts for major depressive disorder and substance disorders.
      This narrowing was significantly related to temporal (major depressive disorder)
      and spatial (substance disorders) variation in gender role traditionality.
      CONCLUSIONS: While gender differences in most lifetime mental disorders were
      fairly stable over the time-space units studied, substantial intercohort
      narrowing of differences in major depression was found to be related to changes
      in the traditionality of female gender roles. Additional research is needed to
      understand why this temporal narrowing was confined to major depression.

PMID- 19581572
TI  - High-pressure photodissociation of water as a tool for hydrogen synthesis and
      fundamental chemistry.
AB  - High-pressure methods have been demonstrated to be efficient in providing new
      routes for the synthesis of materials of technological interest. In several
      molecular compounds, the drastic pressure conditions required for spontaneous
      transformations have been lowered to the kilobar range by photoactivation of the
      reactions. At these pressures, the syntheses are accessible to large-volume
      applications and are of interest to bioscience, space, and environmental
      chemistry. Here, we show that the short-lived hydroxyl radicals, produced in the
      photodissociation of water molecules by near-UV radiation at room temperature and
      pressures of a few tenths of a gigapascal (GPa), can be successfully used to
      trigger chemical reactions in mixtures of water with carbon monoxide or nitrogen.
      The detection of molecular hydrogen among the reaction products is of particular
      relevance. Besides the implications in fundamental chemistry, the mild pressure
      and irradiation conditions, the efficiency of the process, and the nature of the
      reactant and product molecules suggest applications in synthesis.

PMID- 19581573
TI  - Optogenetic control of epileptiform activity.
AB  - The optogenetic approach to gain control over neuronal excitability both in vitro
      and in vivo has emerged as a fascinating scientific tool to explore neuronal
      networks, but it also opens possibilities for developing novel treatment
      strategies for neurologic conditions. We have explored whether such an
      optogenetic approach using the light-driven halorhodopsin chloride pump from
      Natronomonas pharaonis (NpHR), modified for mammalian CNS expression to
      hyperpolarize central neurons, may inhibit excessive hyperexcitability and
      epileptiform activity. We show that a lentiviral vector containing the NpHR gene
      under the calcium/calmodulin-dependent protein kinase IIalpha promoter transduces
      principal cells of the hippocampus and cortex and hyperpolarizes these cells,
      preventing generation of action potentials and epileptiform activity during
      optical stimulation. This study proves a principle, that selective
      hyperpolarization of principal cortical neurons by NpHR is sufficient to curtail
      paroxysmal activity in transduced neurons and can inhibit stimulation train
      induced bursting in hippocampal organotypic slice cultures, which represents a
      model tissue of pharmacoresistant epilepsy. This study demonstrates that the
      optogenetic approach may prove useful for controlling epileptiform activity and
      opens a future perspective to develop it into a strategy to treat epilepsy.

PMID- 19581574
TI  - Asymmetrical cross-resistance between Bacillus thuringiensis toxins Cry1Ac and
      Cry2Ab in pink bollworm.
AB  - Transgenic crops producing Bacillus thuringiensis (Bt) toxins kill some key
      insect pests and can reduce reliance on insecticide sprays. Sustainable use of
      such crops requires methods for delaying evolution of resistance by pests. To
      thwart pest resistance, some transgenic crops produce 2 different Bt toxins
      targeting the same pest. This "pyramid" strategy is expected to work best when
      selection for resistance to 1 toxin does not cause cross-resistance to the other
      toxin. The most widely used pyramid is transgenic cotton producing Bt toxins
      Cry1Ac and Cry2Ab. Cross-resistance between these toxins was presumed unlikely
      because they bind to different larval midgut target sites. Previous results
      showed that laboratory selection with Cry1Ac caused little or no cross-resistance
      to Cry2A toxins in pink bollworm (Pectinophora gossypiella), a major cotton pest.
      We show here, however, that laboratory selection of pink bollworm with Cry2Ab
      caused up to 420-fold cross-resistance to Cry1Ac as well as 240-fold resistance
      to Cry2Ab. Inheritance of resistance to high concentrations of Cry2Ab was
      recessive. Larvae from a laboratory strain resistant to Cry1Ac and Cry2Ab in diet
      bioassays survived on cotton bolls producing only Cry1Ac, but not on cotton bolls
      producing both toxins. Thus, the asymmetrical cross-resistance seen here does not
      threaten the efficacy of pyramided Bt cotton against pink bollworm. Nonetheless,
      the results here and previous evidence indicate that cross-resistance occurs
      between Cry1Ac and Cry2Ab in some key cotton pests. Incorporating the potential
      effects of such cross-resistance in resistance management plans may help to
      sustain the efficacy of pyramided Bt crops.

PMID- 19581575
TI  - Dynamics of locking of peptides onto growing amyloid fibrils.
AB  - Sequence-dependent variations in the growth mechanism and stability of amyloid
      fibrils, which are implicated in a number of neurodegenerative diseases, are
      poorly understood. We have carried out extensive all-atom molecular dynamics
      simulations to monitor the structural changes that occur upon addition of random
      coil (RC) monomer fragments from the yeast prion Sup35 and Abeta-peptide onto a
      preformed fibril. Using the atomic resolution structures of the microcrystals as
      the starting points, we show that the RC --> beta-strand transition for the Sup35
      fragment occurs abruptly over a very narrow time interval, whereas the
      acquisition of strand content is less dramatic for the hydrophobic-rich Abeta
      peptide. Expulsion of water, resulting in the formation of a dry interface
      between 2 adjacent sheets of the Sup35 fibril, occurs in 2 stages. Ejection of a
      small number of discrete water molecules in the second stage follows a rapid
      decrease in the number of water molecules in the first stage. Stability of the
      Sup35 fibril is increased by a network of hydrogen bonds involving both backbone
      and side chains, whereas the marginal stability of the Abeta-fibrils is largely
      due to the formation of weak dispersion interaction between the hydrophobic side
      chains. The importance of the network of hydrogen bonds is further illustrated by
      mutational studies, which show that substitution of the Asn and Gln residues to
      Ala compromises the Sup35 fibril stability. Despite the similarity in the
      architecture of the amyloid fibrils, the growth mechanism and stability of the
      fibrils depend dramatically on the sequence.

PMID- 19581576
TI  - Identification of tumor-associated, MHC class II-restricted phosphopeptides as
      targets for immunotherapy.
AB  - The activation and recruitment of CD4(+) T cells are critical for the development
      of efficient antitumor immunity and may allow for the optimization of current
      cancer immunotherapy strategies. Searching for more optimal and selective targets
      for CD4(+) T cells, we have investigated phosphopeptides, a new category of tumor
      derived epitopes linked to proteins with vital cellular functions. Although MHC I
      restricted phosphopeptides have been identified, it was previously unknown
      whether human MHC II molecules present phosphopeptides for specific CD4(+) T cell
      recognition. We first demonstrated the fine specificity of human CD4(+) T cells
      to discriminate a phosphoresidue by using cells raised against the candidate
      melanoma antigen mutant B-Raf or its phosphorylated counterpart. Then, we
      assessed the presence and complexity of human MHC II-associated phosphopeptides
      by analyzing 2 autologous pairs of melanoma and EBV-transformed B lymphoblastoid
      lines. By using sequential affinity isolation, biochemical enrichment, mass
      spectrometric sequencing, and comparative analysis, a total of 175 HLA-DR
      associated phosphopeptides were characterized. Many were derived from source
      proteins that may have roles in cancer development, growth, and metastasis. Most
      were expressed exclusively by either melanomas or transformed B cells, suggesting
      the potential to define cell type-specific phosphatome "fingerprints." We then
      generated HLA-DRbeta1*0101-restricted CD4(+) T cells specific for a phospho-MART
      1 peptide identified in both melanoma cell lines. These T cells showed
      specificity for phosphopeptide-pulsed antigen-presenting cells as well as for
      intact melanoma cells. This previously undescribed demonstration of MHC II
      restricted phosphopeptides recognizable by human CD4(+) T cells provides
      potential new targets for cancer immunotherapy.

PMID- 19581577
TI  - Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B
      toxicity associated with frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is the most common form of dementia before 60 years
      of age. Rare pathogenic mutations in CHMP2B, which encodes a component of the
      endosomal sorting complex required for transport (ESCRT-III), are associated with
      FTD linked to chromosome 3 (FTD3). Animal models of FTD3 have not yet been
      reported, and what signaling pathways are misregulated by mutant CHMP2B in vivo
      is unknown. Here we report the establishment of a Drosophila model of FTD3 and
      show the genetic interactions between mutant CHMP2B and other components of
      ESCRT. Through an unbiased genome-wide screen, we identified 29 modifier loci and
      found that serpin5 (Spn5), a largely uncharacterized serine protease inhibitor,
      suppresses the melanization phenotype induced by mutant CHMP2B in the fly eye. We
      also found that Spn5 is a negative regulator of the Toll pathway and functions
      extracellularly, likely by blocking the proteolytic activation of Spaetzle, the
      Toll receptor ligand. Moreover, Spn5 inhibited activation of the Toll pathway by
      mutant CHMP2B. Our findings identify Spn5 as a regulator of the Toll pathway and
      CHMP2B toxicity and show that the Toll pathway is a major signaling pathway
      misregulated by mutant CHMP2B in vivo. This fly model will be useful to further
      dissect genetic pathways that are potentially relevant to the pathogenesis and
      treatment of FTD.

PMID- 19581578
TI  - Supply and demand determine the market value of food providers in wild vervet
      monkeys.
AB  - Animals neither negotiate verbally nor conclude binding contracts, but
      nevertheless regularly exchange goods and services without overt coercion and
      manage to arrive at agreements over exchange rates. Biological market theory
      predicts that such exchange rates fluctuate according to the law of supply and
      demand. Previous studies showed that primates pay more when commodities become
      scarcer: subordinates groomed dominants longer before being tolerated at food
      sites in periods of shortage; females groomed mothers longer before obtaining
      permission to handle their infants when there were fewer newborns and males
      groomed fertile females longer before obtaining their compliance when fewer such
      females were present. We further substantiated these results by conducting a 2
      step experiment in 2 groups of free-ranging vervet monkeys in the Loskop Dam
      Nature Reserve, South Africa. We first allowed a single low-ranking female to
      repeatedly provide food to her entire group by triggering the opening of a
      container and measured grooming bouts involving this female in the hour after she
      made the reward available. We then measured the shifts in grooming patterns after
      we added a second food container that could be opened by another low-ranking
      female, the second provider. All 4 providers received more grooming, relative to
      the amount of grooming they provided themselves. As biological market theory
      predicts, the initial gain of first providers was partially lost again after the
      introduction of a second provider in both groups. We conclude that grooming was
      fine-tuned to changes in the value of these females as social partners.

PMID- 19581579
TI  - Stable isotope dietary analysis of the Tianyuan 1 early modern human.
AB  - We report here on the isotopic analysis of the diet of one of the oldest modern
      humans found in Eurasia, the Tianyuan 1 early modern human dating to
      approximately 40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the
      Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human
      and associated faunal remains indicate a diet high in animal protein, and the
      high nitrogen isotope values suggest the consumption of freshwater fish. To
      confirm this inference, we measured the sulfur isotope values of terrestrial and
      freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which
      also support the interpretation of a substantial portion of the diet from
      freshwater fish. This analysis provides the direct evidence for the consumption
      of aquatic resources by early modern humans in China and has implications for
      early modern human subsistence and demography.

PMID- 19581580
TI  - Global discovery of primate-specific genes in the human genome.
AB  - The genomic basis of primate phenotypic uniqueness remains obscure, despite
      increasing genome and transcriptome sequence data availability. Although factors
      such as segmental duplications and positive selection have received much
      attention as potential drivers of primate phenotypes, single-copy primate
      specific genes are poorly characterized. To discover such genes genomewide, we
      screened a catalog of 38,037 human transcriptional units (TUs), compiled from EST
      and cDNA sequences in conjunction with the FANTOM3 transcriptome project. We
      identified 131 TUs from transcribed sequences residing within primate-specific
      insertions in 9-species sequence alignments and outside of segmental
      duplications. Exons of 120 (92%) of the TUs contained interspersed repeats,
      indicating that repeat insertions may have contributed to primate-specific gene
      genesis. Fifty-nine (46%) primate-specific TUs may encode proteins. Although
      primate-specific TU transcript lengths were comparable to known human gene mRNA
      lengths overall, 92 (70%) primate-specific TUs were single-exon. Thirty-two (24%)
      primate-specific TUs were localized to subtelomeric and pericentromeric regions.
      Forty (31%) of the TUs were nested in introns of known genes, indicating that
      primate-specific TUs may arise within older, protein-coding regions. Primate
      specific TUs were preferentially expressed in reproductive organs and tissues (P
      < 0.011), consistent with the expectation that emergence of new, lineage-specific
      genes may accompany speciation or reproduction. Of the 33 primate-specific TUs
      with human Affymetrix microarray probe support, 21 were differentially expressed
      in human teratozoospermia. In addition to elucidating the likely functional
      relevance of primate-specific TUs to reproduction, we present a set of primate
      specific genes for future functional studies, and we implicate nonduplicated
      pericentromeric and subtelomeric regions in gene genesis.

PMID- 19581581
TI  - In-situ measurements of the mixing state and optical properties of soot with
      implications for radiative forcing estimates.
AB  - Our ability to predict how global temperatures will change in the future is
      currently limited by the large uncertainties associated with aerosols. Soot
      aerosols represent a major research focus as they influence climate by absorbing
      incoming solar radiation resulting in a highly uncertain warming effect. The
      uncertainty stems from the fact that the actual amount soot warms our atmosphere
      strongly depends on the manner and degree in which it is mixed with other
      species, a property referred to as mixing state. In global models and inferences
      from atmospheric heating measurements, soot radiative forcing estimates currently
      differ by a factor of 6, ranging between 0.2-1.2 W/m(2), making soot second only
      to CO(2) in terms of global warming potential. This article reports coupled in
      situ measurements of the size-resolved mixing state, optical properties, and
      aging timescales for soot particles. Fresh fractal soot particles dominate the
      measured absorption during peak traffic periods (6-9 AM local time). Immediately
      after sunrise, soot particles begin to age by developing a coating of secondary
      species including sulfate, ammonium, organics, nitrate, and water. Based on these
      direct measurements, the core-shell arrangement results in a maximum absorption
      enhancement of 1.6x over fresh soot. These atmospheric observations help explain
      the larger values for soot forcing measured by others and will be used to obtain
      closure in optical property measurements to reduce one of the largest remaining
      uncertainties in climate change.

PMID- 19581582
TI  - Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of
      stromal p53 and Tsp-1.
AB  - Metastatic tumors can prepare a distant site for colonization via the secretion
      of factors that act in a systemic manner. We hypothesized that non- or weakly
      metastatic human tumor cells may act in an opposite fashion by creating a
      microenvironment in distant tissues that is refractory to colonization. By
      comparing cell lines with different metastatic potential, we have identified a
      tumor-secreted inhibitor of metastasis, prosaposin (Psap), which functions in a
      paracrine and endocrine fashion by stimulating the expression of thrombospondin-1
      (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing
      so in a p53-dependent manner. Introduction of Psap in highly metastatic cells
      significantly reduced the occurrence of metastases, whereas inhibition of Psap
      production by tumor cells was associated with increased metastatic frequency. In
      human prostate cancer, decreased Psap expression was significantly associated
      with metastatic tumors. Our findings suggest that prosaposin, or other agents
      that stimulate p53 activity in the tumor stroma, may be an effective therapy by
      inhibition of the metastatic process.

PMID- 19581583
TI  - Probing the role of the cation-pi interaction in the binding sites of GPCRs using
      unnatural amino acids.
AB  - We describe a general application of the nonsense suppression methodology for
      unnatural amino acid incorporation to probe drug-receptor interactions in
      functional G protein-coupled receptors (GPCRs), evaluating the binding sites of
      both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor.
      Receptors were expressed in Xenopus oocytes, and activation of a G protein
      coupled, inward-rectifying K(+) channel (GIRK) provided, after optimization of
      conditions, a quantitative readout of receptor function. A number of aromatic
      amino acids thought to be near the agonist-binding site were evaluated.
      Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the
      D2 receptor establishes a cation-pi interaction between the agonist dopamine and
      W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with
      proposed "rotamer switch" models. Interestingly, no comparable cation-pi
      interaction was found at the aligning residue in the M2 receptor.

PMID- 19581585
TI  - Predicting Social Security numbers from public data.
AB  - Information about an individual's place and date of birth can be exploited to
      predict his or her Social Security number (SSN). Using only publicly available
      information, we observed a correlation between individuals' SSNs and their birth
      data and found that for younger cohorts the correlation allows statistical
      inference of private SSNs. The inferences are made possible by the public
      availability of the Social Security Administration's Death Master File and the
      widespread accessibility of personal information from multiple sources, such as
      data brokers or profiles on social networking sites. Our results highlight the
      unexpected privacy consequences of the complex interactions among multiple data
      sources in modern information economies and quantify privacy risks associated
      with information revelation in public forums.

PMID- 19581584
TI  - Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset
      degeneration of spinal cord axons.
AB  - Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates
      and effectors produced by localized PI kinase and phosphatase activities.
      Although many signaling roles of PI kinases have been identified in cultured cell
      lines, transgenic animal studies have produced unexpected insight into the in
      vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase
      (PI4K) knockout has previously been reported. Prior studies using cultured cells
      implicated the PI4K2alpha isozyme in diverse functions, including receptor
      signaling, ion channel regulation, endosomal trafficking, and regulated
      secretion. We now show that despite these important functions, mice lacking
      PI4K2alpha kinase activity initially appear normal. However, adult Pi4k2a(GT/GT)
      animals develop a progressive neurological disease characterized by tremor, limb
      weakness, urinary incontinence, and premature mortality. Histological analysis of
      aged Pi4k2a(GT/GT) animals revealed lipofuscin-like deposition and gliosis in the
      cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal,
      but massive axonal degeneration was found in the spinal cord in both ascending
      and descending tracts. These results reveal a previously undescribed role for
      aberrant PI signaling in neurological disease that resembles autosomal recessive
      hereditary spastic paraplegia.

PMID- 19581586
TI  - Sharing global CO2 emission reductions among one billion high emitters.
AB  - We present a framework for allocating a global carbon reduction target among
      nations, in which the concept of "common but differentiated responsibilities"
      refers to the emissions of individuals instead of nations. We use the income
      distribution of a country to estimate how its fossil fuel CO(2) emissions are
      distributed among its citizens, from which we build up a global CO(2)
      distribution. We then propose a simple rule to derive a universal cap on global
      individual emissions and find corresponding limits on national aggregate
      emissions from this cap. All of the world's high CO(2)-emitting individuals are
      treated the same, regardless of where they live. Any future global emission goal
      (target and time frame) can be converted into national reduction targets, which
      are determined by "Business as Usual" projections of national carbon emissions
      and in-country income distributions. For example, reducing projected global
      emissions in 2030 by 13 GtCO(2) would require the engagement of 1.13 billion high
      emitters, roughly equally distributed in 4 regions: the U.S., the OECD minus the
      U.S., China, and the non-OECD minus China. We also modify our methodology to
      place a floor on emissions of the world's lowest CO(2) emitters and demonstrate
      that climate mitigation and alleviation of extreme poverty are largely decoupled.

PMID- 19581587
TI  - A Drosophila model identifies calpains as modulators of the human leukemogenic
      fusion protein AML1-ETO.
AB  - The t(8:21)(q22;q22) translocation is 1 of the most common chromosomal
      abnormalities linked to acute myeloid leukemia (AML). AML1-ETO, the product of
      this translocation, fuses the N-terminal portion of the RUNX transcription factor
      AML1 (also known as RUNX1), including its DNA-binding domain, to the almost
      entire transcriptional corepressor ETO (also known as MTG8 or RUNX1T1). This
      fusion protein acts primarily by interfering with endogenous AML1 function during
      myeloid differentiation, although relatively few genes are known that participate
      with AML1-ETO during leukemia progression. Here, we assessed the consequences of
      expressing this chimera in Drosophila blood cells. Reminiscent of what is
      observed in AML, AML1-ETO specifically inhibited the differentiation of the blood
      cell lineage whose development depends on the RUNX factor Lozenge (LZ) and
      induced increased numbers of LZ(+) progenitors. Using an in vivo RNAi-based
      screen for suppressors of AML1-ETO, we identified calpainB as required for AML1
      ETO-induced blood cell disorders in Drosophila. Remarkably, calpain inhibition
      triggered AML1-ETO degradation and impaired the clonogenic potential of the human
      t(8;21) leukemic blood cell line Kasumi-1. Therefore Drosophila provides a
      promising genetically tractable model to investigate the conserved basis of
      leukemogenesis and to open avenues in AML therapy.

PMID- 19581588
TI  - Insights into the molecular architecture of the 26S proteasome.
AB  - Cryo-electron microscopy in conjunction with advanced image analysis was used to
      analyze the structure of the 26S proteasome and to elucidate its variable
      features. We have been able to outline the boundaries of the ATPase module in the
      "base" part of the regulatory complex that can vary in its position and
      orientation relative to the 20S core particle. This variation is consistent with
      the "wobbling" model that was previously proposed to explain the role of the
      regulatory complex in opening the gate in the alpha-rings of the core particle.
      In addition, a variable mass near the mouth of the ATPase ring has been
      identified as Rpn10, a multiubiquitin receptor, by correlating the electron
      microscopy data with quantitative mass spectrometry.

PMID- 19581589
TI  - Ku86 represses lethal telomere deletion events in human somatic cells.
AB  - Nonhomologous end joining (NHEJ), a form of DNA double-strand break (DSB) repair,
      is conserved from bacteria to humans. One essential NHEJ factor is Ku, which
      consists of a heterodimer of Ku70 and Ku86. In a plethora of model systems, null
      mutations for Ku70 or Ku86 present with defects in DNA DSB repair,
      variable(diversity)joining [V(D)J] recombination, and/or telomere maintenance.
      The complete loss of Ku from bacteria to mice is, however, compatible with
      viability. In striking contrast, human patients with mutations of either Ku
      subunit have never been described. Here, we have used recombinant adeno
      associated virus-mediated gene targeting to produce a human somatic cell line
      that expresses a conditionally null allele of Ku86. The induced loss of Ku86
      results in cell death accompanied by massive telomere loss in the form of t
      circles. Thus, Ku86 is an essential gene in human somatic cells because of its
      requirement, not in NHEJ or V(D)J recombination, but in telomere maintenance.

PMID- 19581590
TI  - Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination
      independent mode, provides clues to proteasome regulation.
AB  - The mechanisms that regulate the ubiquitin (Ub)-proteasome system's own
      components, although critically important, are largely unknown. Ub, a principal
      component of the system, must be maintained at adequate levels to support
      cellular homeostasis under basal and stressed conditions. It was suggested that
      Ub is degraded as part of the polyubiquitin chain along with its substrate. Here,
      we demonstrate in a direct manner that Ub is indeed degraded in a "piggyback"
      mechanism. Also, it has been shown that monomeric Ub can be rapidly degraded when
      a C-terminal tail of a minimal length is fused to it. The tail, which may
      represent the substrate or part of it, or a naturally occurring extended form of
      Ub, probably allows entry of the protein into the 20S catalytic chamber, while Ub
      serves as an anchor to the 19S complex. Here, we show that shorter-tailed Ubs,
      such as UBB(+1), bind to the proteasome but because they cannot be efficiently
      degraded, they inhibit the degradation of other Ub system's substrates such as
      Myc, p21, Mdm2, and MyoD. The inhibition depends on the ability of the tailed Ubs
      to be ubiquitinated: their mere binding to the proteasome is not sufficient.
      Interestingly, the inhibition affects only substrates that must undergo
      ubiquitination for their degradation: ornithine decarboxylase that is targeted by
      the proteasome in a Ub-independent manner, is not affected by the short-tailed
      ubiquitinated Ubs, suggesting it binds to the 19S complex in a site different
      from that to which ubiquitinated substrates bind.

PMID- 19581592
TI  - Should Social Security numbers be replaced by modern, more secure identifiers?

PMID- 19581591
TI  - NPAS3 is a trachealess homolog critical for lung development and homeostasis.
AB  - Trachealess (Trh) is a PAS domain transcription factor regulating Drosophila
      tracheogenesis. No other Trh homolog has been associated with a respiratory
      phenotype. Seeking homolog(s) regulating lung development, we screened murine
      genomic DNA using trh oligonucleotides, identifying only Npas3. Npas3 mRNA peaks
      in lung from E10.5 to E13.5, verified by sequencing, with immunostaining in
      airway epithelial cells. Npas3-null mice have reduced lung branching
      morphogenesis but are viable prenatally. Npas3-null newborns die in respiratory
      distress, with diminished alveolarization, decreased Shh, Fgf9, Fgf10, and Bmp4
      mRNAs, and increased Spry2, consistent with reduced FGF signaling. Exogenous
      FGF10 rescues branching morphogenesis in Npas3-null lungs. In promoter reporter
      assays, NPAS3 directly upregulates Shh and represses Spry2. Npas3(+/-) mice have
      a milder lung phenotype, surviving postnatally, but develop emphysema and airways
      hyperreactivity. Therefore, absence of a developmentally expressed transcription
      factor can alter downstream gene expression and multiple signaling pathways in
      organogenesis. NPAS3 haploinsufficiency may also lead to emphysema and asthma.

PMID- 19581594
TI  - Does cortical thinning in persons at increased risk for major depression also
      increase their risk for Alzheimer's disease?

PMID- 19581593
TI  - Insertion of short transmembrane helices by the Sec61 translocon.
AB  - The insertion efficiency of transmembrane (TM) helices by the Sec61 translocon
      depends on helix amino acid composition, the positions of the amino acids within
      the helix, and helix length. We have used an in vitro expression system to
      examine systematically the insertion efficiency of short polyleucine segments
      (L(n), n = 4 ... 12) flanked at either end by 4-residue sequences of the form
      XXPX-L(n)-XPXX with X = G, N, D, or K. Except for X = K, insertion efficiency (p)
      is <10% for n < 8, but rises steeply to 100% for n = 12. For X = K, p is already
      close to 100% for n = 10. A similar pattern is observed for synthetic peptides
      incorporated into oriented phospholipid bilayer arrays, consistent with the idea
      that recognition of TM segments by the translocon critically involves physical
      partitioning of nascent peptide chains into the lipid bilayer. Molecular dynamics
      simulations suggest that insertion efficiency is determined primarily by the
      energetic cost of distorting the bilayer in the vicinity of the TM helix. Very
      short lysine-flanked leucine segments can reduce the energetic cost by extensive
      hydrogen bonding with water and lipid phosphate groups (snorkeling) and by
      partial unfolding.

PMID- 19581595
TI  - Out of Africa: modern human origins special feature: middle and later Pleistocene
      hominins in Africa and Southwest Asia.
AB  - Approximately 700,000 years ago, Homo erectus in Africa was giving way to
      populations with larger brains accompanied by structural adjustments to the
      vault, cranial base, and face. Such early Middle Pleistocene hominins were not
      anatomically modern. Their skulls display strong supraorbital tori above
      projecting faces, flattened frontals, and less parietal expansion than is the
      case for Homo sapiens. Postcranial remains seem also to have archaic features.
      Subsequently, some groups evolved advanced skeletal morphology, and by ca.
      200,000 years ago, individuals more similar to recent humans are present in the
      African record. These fossils are associated with Middle Stone Age lithic
      assemblages and, in some cases, Acheulean tools. Crania from Herto in Ethiopia
      carry defleshing cutmarks and superficial scoring that may be indicative of
      mortuary practices. Despite these signs of behavioral innovation, neither the
      Herto hominins, nor others from Late Pleistocene sites such as Klasies River in
      southern Africa and Skhul/Qafzeh in Israel, can be matched in living populations.
      Skulls are quite robust, and it is only after approximately 35,000 years ago that
      people with more gracile, fully modern morphology make their appearance. Not
      surprisingly, many questions concerning this evolutionary history have been
      raised. Attention has centered on systematics of the mid-Pleistocene hominins,
      their paleobiology, and the timing of dispersals that spread H. sapiens out of
      Africa and across the Old World. In this report, I discuss structural changes
      characterizing the skulls from different time periods, possible regional
      differences in morphology, and the bearing of this evidence on recognizing
      distinct species.

PMID- 19581596
TI  - Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid
      interaction required for encapsidation.
AB  - Human APOBEC3 (A3) proteins form part of the intrinsic immunity to retroviruses.
      Carrying 1 or 2 copies of a cytidine deaminase motif, A3s act by deamination of
      retroviral genomes during reverse transcription. HIV-1 overcomes this inhibition
      by the Vif protein, which prevents incorporation of A3 into virions. In this
      study we modeled and probed the structure of APOBEC3C (A3C), a single-domain A3
      with strong antilentiviral activity. The 3-dimensional protein model was used to
      predict the effect of mutations on antiviral activity, which was tested in a
      Deltavif simian immunodeficiency virus (SIV) reporter virus assay. We found that
      A3C activity requires protein dimerization for antiviral activity against SIV.
      Furthermore, by using a structure-based algorithm for automated pocket
      extraction, we detected a putative substrate binding pocket of A3C distal from
      the zinc-coordinating deaminase motif. Mutations in this region diminished
      antiviral activity by excluding A3C from virions. We found evidence that the
      small 5.8S RNA specifically binds to this locus and mediates incorporation of A3C
      into virus particles.

PMID- 19581597
TI  - Expression of immediate-early genes reveals functional compartments within ocular
      dominance columns after brief monocular inactivation.
AB  - Visual inputs from the 2 eyes in most primates activate alternating bands of
      cortex in layer 4C of primary visual cortex, thereby forming the well-studied
      ocular dominance columns (ODCs). In addition, the enzymatic reactivity of
      cytochrome oxidase (CO) reveals "blob" structures within the supragranular layers
      of ODCs. Here, we present evidence for compartments within ODCs that have not
      been clearly defined previously. These compartments are revealed by the activity
      dependent mRNA expression of immediate-early genes (IEGs), zif268 and c-fos,
      after brief periods of monocular inactivation (MI). After a 1-3-h period of MI
      produced by an injection of tetrodotoxin, IEGs were expressed in a patchy pattern
      that included infragranular layers, as well as supragranular layers, where they
      corresponded to the CO blobs. In addition, the expressions of IEGs in layer 4C
      were especially high in narrow zones along boundaries of ODCs, referred to here
      as the "border strips" of the ODCs. After longer periods of MI (>5 h), the border
      strips were no longer apparent. When either eyelid was sutured, changes in IEG
      expression were not evident in layer 4C; however, the patchy pattern of the
      expression in the infragranular and supragranular layers remained. These changes
      of IEG expression after MI indicate that cortical circuits involving the CO blobs
      of the supragranular layers include aligned groups of neurons in the
      infragranular layers and that the border strip neurons of layer 4C are highly
      active for a 3-h period after MI.

PMID- 19581598
TI  - Large-scale production and study of a synthetic G protein-coupled receptor: human
      olfactory receptor 17-4.
AB  - Although understanding of the olfactory system has progressed at the level of
      downstream receptor signaling and the wiring of olfactory neurons, the system
      remains poorly understood at the molecular level of the receptors and their
      interaction with and recognition of odorant ligands. The structure and functional
      mechanisms of these receptors still remain a tantalizing enigma, because numerous
      previous attempts at the large-scale production of functional olfactory receptors
      (ORs) have not been successful to date. To investigate the elusive biochemistry
      and molecular mechanisms of olfaction, we have developed a mammalian expression
      system for the large-scale production and purification of a functional OR protein
      in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4)
      purified from a HEK293S tetracycline-inducible system. Scale-up of production
      yield was achieved through suspension culture in a bioreactor, which enabled the
      preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size
      exclusion chromatography, with expression yields reaching 3 mg/L of culture
      medium. Several key post-translational modifications were identified using MS,
      and CD spectroscopy showed the receptor to be approximately 50% alpha-helix,
      similar to other recently determined G protein-coupled receptor structures.
      Detergent-solubilized hOR17-4 specifically bound its known activating odorants
      lilial and floralozone in vitro, as measured by surface plasmon resonance. The
      hOR17-4 also recognized specific odorants in heterologous cells as determined by
      calcium ion mobilization. Our system is feasible for the production of large
      quantities of OR necessary for structural and functional analyses and research
      into OR biosensor devices.

PMID- 19581599
TI  - Effective preexposure and postexposure prophylaxis of rabies with a highly
      attenuated recombinant rabies virus.
AB  - Rabies remains an important public health problem with more than 95% of all human
      rabies cases caused by exposure to rabid dogs in areas where effective,
      inexpensive vaccines are unavailable. Because of their ability to induce strong
      innate and adaptive immune responses capable of clearing the infection from the
      CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could
      be particularly useful not only for the global eradication of canine rabies but
      also for late-stage rabies postexposure prophylaxis of humans. To overcome
      concerns regarding the safety of live-attenuated RV vaccines, we developed the
      highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most
      attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely
      nonpathogenic after intracranial infection of mice that are either
      developmentally immunocompromised (e.g., 5-day-old mice) or have inherited
      deficits in immune function (e.g., antibody production or type I IFN signaling),
      as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune
      mechanisms capable of containing a CNS infection with pathogenic RV, thereby
      preventing lethal rabies encephalopathy. The lack of pathogenicity together with
      excellent immunogenicity and the capacity to deliver immune effectors to CNS
      tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the
      preexposure and postexposure prophylaxis of rabies.

PMID- 19581600
TI  - Resources and energetics determined dinosaur maximal size.
AB  - Some dinosaurs reached masses that were approximately 8 times those of the
      largest, ecologically equivalent terrestrial mammals. The factors most
      responsible for setting the maximal body size of vertebrates are resource quality
      and quantity, as modified by the mobility of the consumer, and the vertebrate's
      rate of energy expenditure. If the food intake of the largest herbivorous mammals
      defines the maximal rate at which plant resources can be consumed in terrestrial
      environments and if that limit applied to dinosaurs, then the large size of
      sauropods occurred because they expended energy in the field at rates
      extrapolated from those of varanid lizards, which are approximately 22% of the
      rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2
      species having the same energy income, the species that uses the most energy for
      mass-independent maintenance of necessity has a smaller size. The larger mass
      found in some marine mammals reflects a greater resource abundance in marine
      environments. The presumptively low energy expenditures of dinosaurs potentially
      permitted Mesozoic communities to support dinosaur biomasses that were up to 5
      times those found in mammalian herbivores in Africa today. The maximal size of
      predatory theropods was approximately 8 tons, which if it reflected the maximal
      capacity to consume vertebrates in terrestrial environments, corresponds in
      predatory mammals to a maximal mass less than a ton, which is what is observed.
      Some coelurosaurs may have evolved endothermy in association with the evolution
      of feathered insulation and a small mass.

PMID- 19581603
TI  - Association between statin-associated myopathy and skeletal muscle damage.
AB  - BACKGROUND: Many patients taking statins often complain of muscle pain and
      weakness. The extent to which muscle pain reflects muscle injury is unknown.
      METHODS: We obtained biopsy samples from the vastus lateralis muscle of 83
      patients. Of the 44 patients with clinically diagnosed statin-associated
      myopathy, 29 were currently taking a statin, and 15 had discontinued statin
      therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also
      included 19 patients who were taking statins and had no myopathy, and 20 patients
      who had never taken statins and had no myopathy. We classified the muscles as
      injured if 2% or more of the muscle fibres in a biopsy sample showed damage.
      Using reverse transcriptase polymerase chain reaction, we evaluated the
      expression levels of candidate genes potentially related to myocyte injury.
      RESULTS: Muscle injury was observed in 25 (of 44) patients with myopathy and in 1
      patient without myopathy. Only 1 patient with structural injury had a circulating
      level of creatine phosphokinase that was elevated more than 1950 U/L (10x the
      upper limit of normal). Expression of ryanodine receptor 3 was significantly
      upregulated in patients with biopsy evidence of structural damage (1.7, standard
      error of the mean 0.3). INTERPRETATION: Persistent myopathy in patients taking
      statins reflects structural muscle damage. A lack of elevated levels of
      circulating creatine phosphokinase does not rule out structural muscle injury.
      Upregulation of the expression of ryanodine receptor 3 is suggestive of an
      intracellular calcium leak.

PMID- 19581601
TI  - Neuroprotective natural antibodies to assemblies of amyloidogenic peptides
      decrease with normal aging and advancing Alzheimer's disease.
AB  - A number of distinct beta-amyloid (Abeta) variants or multimers have been
      implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides
      are in clinical trials. Humans have natural Abeta-specific antibodies, but their
      diversity, abundance, and function in the general population remain largely
      unknown. Here, we demonstrate with peptide microarrays the presence of natural
      antibodies against known toxic Abeta and amyloidogenic non-Abeta species in
      plasma samples and cerebrospinal fluid of AD patients and healthy controls aged
      21-89 years. Antibody reactivity was most prominent against oligomeric assemblies
      of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric
      preparations of Abeta1-42 in particular declined with age and advancing AD. Most
      individuals showed unexpected antibody reactivities against peptides unique to
      autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated
      from plasma of AD patients or healthy controls protected primary neurons from
      Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies
      against amyloid peptides, and after immunization with Abeta the monkeys developed
      high titers not only against Abeta peptides but also against ABri and ADan
      peptides. Our findings support the concept of conformation-specific, cross
      reactive antibodies that may protect against amyloidogenic toxic peptides. If a
      therapeutic benefit of Abeta antibodies can be confirmed in AD patients,
      stimulating the production of such neuroprotective antibodies or passively
      administering them to the elderly population may provide a preventive measure
      toward AD.

PMID- 19581606
TI  - Worrisome outbreak of river blindness in northern Uganda.

PMID- 19581607
TI  - Charter challenge of ban on direct-to-consumer advertising to be heard by Ontario
      court in mid-June.

PMID- 19581604
TI  - Long-term trends in use of and expenditures for cardiovascular medications in
      Canada.
AB  - BACKGROUND: Medication expenditures have become the fastest growing sector of
      costs within the Canadian health care system. Evaluation of the use of
      cardiovascular medications is important to determine the magnitude of the growth,
      to identify which medications dominate the landscape and to detect
      interprovincial differences in utilization. We describe long-term trends in the
      use of and expenditures for cardiovascular medications in Canada, by drug class
      and by province. METHODS: For these analyses, we used volume and expenditure data
      related to prescriptions for cardiovascular medications obtained from IMS Health
      Canada's CompuScript Audit database for the period 1996-2006. Here, we describe
      national and provincial patterns of utilization and expenditures for specified
      classes of cardiovascular medications. RESULTS: The use of cardiovascular
      medications increased sharply in Canada during the study period, with related
      costs rising by over 200% during this period to surpass $5 billion in 2006.
      Changes in population demographics, risk factors and inflation appeared to
      account for about two-thirds of the observed growth in expenditures. Use of newer
      medication classes (statins, angiotensin-receptor blockers, angiotensin
      converting-enzyme inhibitors), for which patented brand name medications
      predominate, accounted for almost one-third of the cost increases.
      Interprovincial differences in total expenditures for cardiovascular drugs
      portrayed a descending gradient from east to west, with greatest variability for
      the newer drug classes. INTERPRETATION: Prescriptions and expenditures for
      cardiovascular medications in Canada escalated over the study period. Projected
      increases may reach potentially unsustainable levels. Greater emphasis on the use
      of cost-effective medications is required to limit further increases. Factors
      influencing interprovincial differences warrant further study.

PMID- 19581608
TI  - Canadian therapist trains teachers to help heal traumatized Afghan students.

PMID- 19581609
TI  - White mud letter to a dear dead friend.

PMID- 19581612
TI  - Rational use of medications: if Canada can't do it ...

PMID- 19581613
TI  - Improving primary care for patients with complex chronic diseases: can health
      information technology play a role?

PMID- 19581614
TI  - The perils of poultry.

PMID- 19581616
TI  - India struggles to quash dirty syringe industry.

PMID- 19581619
TI  - Exacerbation of psoriasis with beta-blocker therapy.

PMID- 19581618
TI  - Individualized electronic decision support and reminders to improve diabetes care
      in the community: COMPETE II randomized trial.
AB  - BACKGROUND: Diabetes mellitus is a complex disease with serious complications.
      Electronic decision support, providing information that is shared and discussed
      by both patient and physician, encourages timely interventions and may improve
      the management of this chronic disease. However, it has rarely been tested in
      community-based primary care. METHODS: In this pragmatic randomized trial, we
      randomly assigned adult primary care patients with type 2 diabetes to receive the
      intervention or usual care. The intervention involved shared access by the
      primary care provider and the patient to a Web-based, colour-coded diabetes
      tracker, which provided sequential monitoring values for 13 diabetes risk
      factors, their respective targets and brief, prioritized messages of advice. The
      primary outcome measure was a process composite score. Secondary outcomes
      included clinical composite scores, quality of life, continuity of care and
      usability. The outcome assessors were blinded to each patient's intervention
      status. RESULTS: We recruited sequentially 46 primary care providers and then 511
      of their patients (mean age 60.7 [standard deviation 12.5] years). Mean follow-up
      was 5.9 months. The process composite score was significantly better for patients
      in the intervention group than for control patients (difference 1.27, 95%
      confidence interval [CI] 0.79-1.75, p < 0.001); 61.7% (156/253) of patients in
      the intervention group, compared with 42.6% (110/258) of control patients, showed
      improvement (difference 19.1%, p < 0.001). The clinical composite score also had
      significantly more variables with improvement for the intervention group (0.59,
      95% CI 0.09-1.10, p = 0.02), including significantly greater declines in blood
      pressure (-3.95 mm Hg systolic and -2.38 mm Hg diastolic) and glycated hemoglobin
      (-0.2%). Patients in the intervention group reported greater satisfaction with
      their diabetes care. INTERPRETATION: A shared electronic decision-support system
      to support the primary care of diabetes improved the process of care and some
      clinical markers of the quality of diabetes care. (ClinicalTrials.gov trial
      register no. NCT00813085.).

PMID- 19581620
TI  - No options for sleep.

PMID- 19581622
TI  - Primary care reform.

PMID- 19581624
TI  - South Africa's womb.

PMID- 19581625
TI  - Ponziceuticals within the medical industrial complex.

PMID- 19581626
TI  - Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic
      cells via down-regulation of heat shock protein 70.
AB  - Type I IFNs play a key role in linking the innate and adaptive arms of the immune
      system. Although produced rapidly in response to pathogens, IFNs are also
      produced at low levels in the absence of infection. In the present study, we
      demonstrate that constitutively produced IFNs are necessary in vivo to maintain
      dendritic cells in an "Ag presentation-competent" state. Conventional dendritic
      cells (cDCs) isolated from spleens of IFN-beta or IFNAR-deficient mice exhibit a
      highly impaired ability to present Ag and activate naive T cells. Microarray
      analysis of mRNA isolated from IFN-beta(-/-) and IFNAR(-/-) cDCs revealed
      diminished expression of two genes that encoded members of the heat shock protein
      70 (Hsp70) family. Consistent with this observation, pharmacological inhibition
      of Hsp70 in cDCs from wild-type mice impaired their T cell stimulatory capacity.
      Similarly, the Ag presentation ability of splenic cDCs isolated from Hsp70.1/3(-/
      ) mice was also severely impaired in comparison to wild-type cDCs. Thus,
      constitutive IFN-beta expression regulates Hsp70 levels to help maintain
      dendritic cells in a competent state for efficient priming of effector T cells in
      vivo.

PMID- 19581627
TI  - Cellular inflammatory response to flaviviruses in the central nervous system of a
      primate host.
AB  - Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus,
      West Nile virus, and St. Louis encephalitis virus are important neurotropic human
      pathogens, typically causing a devastating and often fatal neuroinfection.
      Flaviviruses induce neuroinflammation with typical features of viral
      encephalitides, including inflammatory cell infiltration, activation of
      microglia, and neuronal degeneration. Development of safe and effective live
      virus vaccines against neurotropic flavivirus infections demands a detailed
      knowledge of their neuropathogenesis in a primate host that is evolutionarily
      close to humans. Here, we used computerized morphometric analysis to
      quantitatively assess the cellular inflammatory responses in the central nervous
      system (CNS) of rhesus monkeys infected with three antigenically divergent
      attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of
      microglial activation, trafficking of T and B cells, and changes in T cell
      subsets within the CNS define unique phenotypic signatures for each of the three
      viruses. Our results provide a benchmark for investigation of cellular
      inflammatory responses induced by attenuated flaviviruses in the CNS of primate
      hosts and provide insight into the neuropathogenesis of flavivirus encephalitis
      that might guide the development of safe and effective live-virus vaccines.

PMID- 19581628
TI  - Association of AMP-activated protein kinase subunits with glycogen particles as
      revealed in situ by immunoelectron microscopy.
AB  - Immunogold cytochemistry was applied to reveal the intracellular location of AMP
      activated protein kinase (AMPK) subunits in liver tissue of normal rats fed ad
      libitum. AMPK alpha and beta subunits were located both in the cytosol and in
      close association with rosettes of glycogen particles (alpha particles). To
      reveal their true in situ association with glycogen, particular tissue processing
      conditions that retain glycogen in the cells were required. These included
      fixation with a combination of glutaraldehyde and paraformaldehyde, followed by
      postfixation with osmium tetroxide and lead citrate and embedding in Epon.
      Processing by less-stringent fixation conditions and embedding in Lowicryl led to
      the extraction of the glycogen deposits, which in turn resulted in the absence of
      any labeling. This indicates that the loss of glycogen deposits leads to the loss
      of closely associated proteins. Labeling for the alpha(1) and alpha(2) subunits
      of AMPK was found to be about 2-fold greater over glycogen than over cytosol,
      whereas labeling for beta(1) was 8-fold higher over the glycogen particles than
      over the cytosol. Immunogold combined with morphometric analysis demonstrated
      that the beta(1) subunits are located at the periphery of the glycogen rosettes,
      consistent with a recent hypothesis developed via biochemical approaches.

PMID- 19581629
TI  - Organization of hyaluronan and versican in the extracellular matrix of human
      fibroblasts treated with the viral mimetic poly I:C.
AB  - We have examined structural details of hyaluronan- and versican-rich pericellular
      matrices in human lung fibroblasts, as well as fixation effects after treatment
      with the viral mimetic, poly I:C. Lateral aggregation of hyaluronan chains was
      promoted by acid-ethanol-formalin fixation compared with a network appearance
      with formalin alone. However, hyaluronidase-sensitive cable structures were seen
      in live cells, suggesting that they are not a fixation artifact. With all
      fixatives, versican and hyaluronan probes bound alternately along strands
      extending from the plasma membrane. However, a yellow colocalization signal
      required aggregation/overlap of several hyaluronan/versican strands and was more
      pronounced after acid-ethanol-formalin fixation. In addition to the main cell
      surface, hyaluronan and versican were also associated with fine actin-positive
      membrane protrusions, retraction fibers, and surface blebs. After wounding plus
      treatment with poly I:C, cells displayed larger hyaluronan coats and cable-like
      structures, as well as more membrane protrusions. However, treated cells did not
      migrate and had increased stress fibers compared with control wounded cells.
      Deposition of hyaluronan into cable-like structures in response to poly I:C was
      diminished but still apparent following actin filament disruption with
      cytochalasin D, suggesting that the protrusions only partially facilitate cable
      formation. As seen by scanning electron microscopy, the membrane protrusions may
      participate in poly I:C-induced binding of monocytes to hyaluronan- and versican
      rich matrices. These results suggest that poly I:C-induced hyaluronan- and
      versican-rich cable structures are not deposited during migration, and that
      cellular protrusions partially contribute to hyaluronan cable formation. This
      manuscript contains online supplemental material at http://www.jhc.org. Please
      visit this article online to view these materials.

PMID- 19581630
TI  - The in vivo expression of dipeptidyl peptidases 8 and 9.
AB  - The dipeptidyl peptidase IV (DPIV) enzyme family contains both potential and
      proven therapeutic targets. Recent reports indicate the presence of DP8 and DP9
      in peripheral blood lymphocytes, testis, lung, and brain. For a more
      comprehensive understanding of DP8 and DP9 tissue and cellular expression, mRNA
      and enzyme activity were examined. Many organs from C57BL/6 wild-type and DPIV
      gene-knockout mice were examined; DP8/9 enzyme activity was detected in the
      immune system, brain, testis, muscle, and epithelia. In situ hybridization
      localized DP8 and DP9 mRNA to lymphocytes and epithelial cells in liver,
      gastrointestinal tract, lymph node, spleen, and lung. DP8 and DP9 mRNA was
      detected in baboon and mouse testis, and DP9 expression was elevated in human
      testicular cancers. DP8 and DP9 mRNA were ubiquitous in day 17 mouse embryo, with
      greatest expression in epithelium (skin and gastrointestinal tract) and brain.
      Thus, DP8 and DP9 are widely expressed enzymes. Their expression in lymphocytes
      and epithelia indicates potential for roles in the digestive and immune systems.
      This manuscript contains online supplemental material at http://www.jhc.org.
      Please visit this article online to view these materials.

PMID- 19581631
TI  - Stepped-dose versus full-dose efavirenz for HIV infection and neuropsychiatric
      adverse events: a randomized trial.
AB  - BACKGROUND: More than 50% of patients who start efavirenz treatment develop
      limiting neuropsychiatric adverse events (NPAEs). OBJECTIVE: To assess whether
      stepwise dosing of efavirenz decreases the incidence and severity of NPAEs while
      maintaining virologic efficacy. DESIGN: Randomized, double-blind, controlled
      trial. SETTING: 7 HIV clinics in Spain. PATIENTS: 114 HIV-infected patients
      eligible for efavirenz treatment plus 2 nucleoside or nucleotide reverse
      transcriptase inhibitors. INTERVENTION: Random assignment (by computer-generated
      sequence) to receive efavirenz, 200 mg/d on days 1 through 6, 400 mg/d on days 7
      through 13, and 600 mg/d on day 14 and after, or efavirenz, 600 mg/d, from day 1.
      Both groups received 2 nucleoside or nucleotide reverse transcriptase inhibitors
      chosen by the patient's physician. MEASUREMENTS: Neuropsychiatric symptoms and
      sleep quality were assessed by questionnaires at 0, 7, 14, and 30 days. The
      primary outcome was efavirenz-related NPAEs during the first 2 weeks, and the
      secondary outcome was plasma HIV RNA level at 24 weeks. RESULTS: Compared with
      the stepped-dose group, the full-dose group had higher incidence and severity of
      dizziness (66.0% vs. 32.8%; P = 0.001), hangover (45.8% vs. 20.7%; P = 0.008),
      impaired concentration (22.9% vs. 8.9%; P = 0.038), and hallucinations (6.1% vs.
      0%; P = 0.056) during the first week. From week 2, the incidence of efavirenz
      related NPAEs was similar in both groups, although the severity was greater in
      the full-dose group. Virologic and immunologic efficacy seemed similar in both
      groups. LIMITATIONS: The sample size was calculated on the basis of a high
      absolute difference in rates of efavirenz-related NPAEs between the groups. A
      lower absolute difference and a larger sample size could have made the
      differences between groups reach statistical significance beyond the first week.
      In addition, the sample size does not allow confirmation of similar efficacy
      between treatment groups. CONCLUSION: Stepwise dose escalation of efavirenz over
      2 weeks reduces the incidence and intensity of efavirenz-related NPAEs while
      maintaining efficacy. PRIMARY FUNDING SOURCE: Consejeria de Salud, Junta de
      Andalucia, Spain.

PMID- 19581632
TI  - Comparison of side effects with 2 doses of the HIV drug efavirenz.

PMID- 19581633
TI  - Meta-analysis: travel and risk for venous thromboembolism.
AB  - BACKGROUND: The potential risk for travel-related venous thromboembolism (VTE)
      has become an important public health concern because of rapid increases in long
      distance travel; however, previous studies on this relationship are surprisingly
      contradictory. PURPOSE: To estimate the risk for VTE in travelers, determine
      whether a dose-response relationship exists, and identify reasons for the
      contradictory results of previous studies. DATA SOURCES: MEDLINE, EMBASE, BIOSIS,
      CINAHL, grey-literature sources, contact with investigators, and reference lists
      of studies, without language restrictions. STUDY SELECTION: Reports were selected
      if they investigated the association between travel and VTE for persons who used
      any mode of transportation and if nontraveling persons were included for
      comparison. DATA EXTRACTION: Data on study and patient characteristics, risk
      estimates, and quality were independently extracted by 2 investigators. Pooled
      effect estimates were obtained by using random-effect meta-analysis. DATA
      SYNTHESIS: Of 1560 identified abstracts, 14 studies (11 case-control, 2 cohort,
      and 1 case-crossover) met inclusion criteria, including 4055 cases of VTE.
      Compared with nontravelers, the overall pooled relative risk for VTE in travelers
      was 2.0 (95% CI, 1.5 to 2.7). Significant heterogeneity was present because of
      the method for selecting control participants (P = 0.008): whether the studies
      used control participants who had been referred for VTE evaluation or nonreferred
      control participants. When the studies that used referred control participants
      were excluded, the pooled relative risk for VTE in travelers was 2.8 (CI, 2.2 to
      3.7), without significant heterogeneity. A dose-response relationship was
      identified, with an 18% higher risk for VTE for each 2-hour increase in duration
      of travel by any mode (P = 0.010) and a 26% higher risk for every 2 hours of air
      travel (P = 0.005). LIMITATION: All available studies were from Western
      countries; generalizability to non-Western populations is expected but needs
      confirmation. CONCLUSION: Travel is associated with a nearly 3-fold higher risk
      for VTE, with a dose-response relationship of 18% higher risk for each 2-hour
      increase in travel duration. Heterogeneity in results of previous studies was due
      to selection bias toward the null from use of referred control participants.

PMID- 19581634
TI  - Travel and venous thrombosis: an exercise in thinking about bias.

PMID- 19581635
TI  - Systematic review: comparative effectiveness of radiofrequency catheter ablation
      for atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia. Medical
      treatment often fails to control symptoms. PURPOSE: To compare the benefits and
      harms of radiofrequency catheter ablation and medical therapy in adults with
      atrial fibrillation. DATA SOURCES: MEDLINE and the Cochrane Central Register of
      Controlled Trials (2000 to December 2008) were searched for English-language
      reports of studies in adults. STUDY SELECTION: 6 independent reviewers screened
      abstracts to identify longitudinal studies of adults with atrial fibrillation who
      underwent radiofrequency catheter ablation. Studies reported arrhythmia or other
      cardiovascular outcomes at least 6 months after ablation or any adverse events.
      DATA EXTRACTION: Data were extracted by 1 of 4 reviewers and were verified by a
      cardiac electrophysiologist. Study quality and overall strength of evidence for
      each question were rated by 2 independent reviewers; disagreements were resolved
      by consensus. DATA SYNTHESIS: 108 studies met eligibility criteria. Moderate
      strength of evidence (3 trials; n = 30 to 198) showed that radiofrequency
      ablation after a failed drug course was more likely than continuation of drug
      therapy alone to lead to maintained sinus rhythm. Low strength of evidence (4
      trials [n = 30 to 137] and 1 retrospective study [n = 1171]) suggested that
      radiofrequency ablation improved quality of life, promoted avoidance of
      anticoagulation, and decreased readmission rates compared with medical treatment.
      Major adverse events occurred in fewer than 5% of patients in most of 84 studies.
      LIMITATIONS: Study follow-up was generally 12 months or less. Large heterogeneity
      of applied techniques and reporting of outcomes precluded many definitive
      conclusions. Reporting of adverse events was poor. Publication and selective
      reporting biases could not be ruled out. Studies with small samples and studies
      reported in a language other than English were excluded. CONCLUSION:
      Radiofrequency catheter ablation is effective for up to 12 months of rhythm
      control when used as a second-line therapy for atrial fibrillation in relatively
      young patients with near-intact cardiac function. Longer studies that use primary
      end points of stroke and mortality are needed.

PMID- 19581637
TI  - Positron emission tomography plus computed tomography for staging early lung
      cancer.

PMID- 19581636
TI  - Positron emission tomography in staging early lung cancer: a randomized trial.
AB  - BACKGROUND: Among patients with early-stage non-small cell lung cancer (NSCLC),
      preoperative imaging tests are important in defining surgical candidates.
      OBJECTIVE: To assess whether whole-body positron emission tomography and computed
      tomography (PET-CT) plus cranial imaging correctly upstages cancer in more
      patients with NSCLC than does conventional staging plus cranial imaging. DESIGN:
      Randomized clinical trial with recruitment from June 2004 to August 2007. The
      centralized, computer-generated, variable block size randomization scheme was
      stratified by treatment center and cancer stage. Participants, health care
      providers, and outcome assessors were not blinded to imaging modality assignment.
      SETTING: 8 hospitals and 5 PET-CT centers in academic institutions. PATIENTS:
      Eligible patients were older than 18 years; had histologic or cytologic proof of
      stage I, II, or IIIA NSCLC on the basis of chest radiography and thoracic CT; and
      had a tumor considered to be resectable. INTERVENTION: PET-CT or conventional
      staging (abdominal CT and bone scan). All patients also had cranial imaging using
      CT or magnetic resonance imaging. MEASUREMENTS: The primary outcome was correct
      upstaging, thereby avoiding stage-inappropriate surgery. Secondary outcomes were
      incorrect upstaging and incorrect understaging. RESULTS: 170 patients were
      assigned to PET-CT and 167 to conventional staging. Eight patients (3 who had PET
      CT and 5 who had conventional staging) did not have planned surgery. Disease was
      correctly upstaged in 23 of 167 PET-CT recipients and 11 of 162 conventional
      staging recipients (13.8% vs. 6.8%; difference, 7.0 percentage points [95% CI,
      0.3 to 13.7 percentage points]), thereby sparing these patients from surgery.
      Disease was incorrectly upstaged in 8 PET-CT recipients and 1 conventional
      staging recipient (4.8% vs. 0.6%; difference, 4.2 percentage points [CI, 0.5 to
      8.6 percentage points]), and it was incorrectly understaged in 25 and 48
      patients, respectively (14.9% vs. 29.6%; difference, 14.7 percentage points [CI,
      5.7 to 23.4 percentage points]). At 3 years, 52 patients who had PET-CT and 57
      patients who had conventional staging had died. LIMITATION: The relatively small
      sample and the fact that some patients did not have planned surgery limited the
      ability to determine precise differences in clinical outcomes that were
      attributable to testing strategies. CONCLUSION: Preoperative staging with PET-CT
      and cranial imaging identifies more patients with mediastinal and extrathoracic
      disease than conventional staging, thereby sparing more patients from stage
      inappropriate surgery, but the strategy also incorrectly upstaged disease in more
      patients.

PMID- 19581638
TI  - The PET and the pendulum.

PMID- 19581639
TI  - Dissecting an allosteric switch in caspase-7 using chemical and mutational
      probes.
AB  - Apoptotic caspases, such as caspase-7, are stored as inactive protease zymogens,
      and when activated, lead to a fate-determining switch to induce cell death. We
      previously discovered small molecule thiol-containing inhibitors that when
      tethered revealed an allosteric site and trapped a conformation similar to the
      zymogen form of the enzyme. We noted three structural transitions that the
      compounds induced: (i) breaking of an interaction between Tyr-223 and Arg-187 in
      the allosteric site, which prevents proper ordering of the catalytic cysteine;
      (ii) pinning the L2' loop over the allosteric site, which blocks critical
      interactions for proper ordering of the substrate-binding groove; and (iii) a
      hinge-like rotation at Gly-188 positioned after the catalytic Cys-186 and Arg
      187. Here we report a systematic mutational analysis of these regions to dissect
      their functional importance to mediate the allosteric transition induced by these
      compounds. Mutating the hinge Gly-188 to the restrictive proline causes a massive
      approximately 6000-fold reduction in catalytic efficiency. Mutations in the Arg
      187-Tyr-223 couple have a far less dramatic effect (3-20-fold reductions).
      Interestingly, although the allosteric couple mutants still allow binding and
      allosteric inhibition, they partially relieve the mutual exclusivity of binding
      between inhibitors at the active and allosteric sites. These data highlight a
      small set of residues critical for mediating the transition from active to
      inactive zymogen-like states.

PMID- 19581641
TI  - Screening older adults for eyesight problems: U.S. preventive services task force
      recommendation.

PMID- 19581640
TI  - Role of dimerization in the catalytic properties of the Escherichia coli
      disulfide isomerase DsbC.
AB  - The bacterial protein-disulfide isomerase DsbC is a homodimeric V-shaped enzyme
      that consists of a dimerization domain, two alpha-helical linkers, and two
      opposing thioredoxin fold catalytic domains. The functional significance of the
      two catalytic domains of DsbC is not well understood yet. We have engineered
      heterodimer-like DsbC derivatives covalently linked via (Gly(3)-Ser) flexible
      linkers. We either inactivated one of the catalytic sites (CGYC), or entirely
      removed one of the catalytic domains while maintaining the putative binding area
      intact. Variants having a single active catalytic site display significant levels
      of isomerase activity. Furthermore, mDsbC[H45D]-dim[D53H], a DsbC variant lacking
      an entire catalytic domain but with an intact dimerization domain, also showed
      isomerase activity, albeit at lower levels. In addition, the absence of the
      catalytic domain allowed this protein to catalyze in vivo oxidation. Our results
      reveal that two catalytic domains in DsbC are not essential for disulfide bond
      isomerization and that a determining feature in isomerization is the availability
      of a substrate binding domain.

PMID- 19581642
TI  - In the clinic. Preoperative evaluation.
AB  - The content of In the Clinic is drawn from the clinical information and education
      resources of the American College of Physicians (ACP), including PIER
      (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and
      Self Assessment Program). Annals of Internal Medicine editors develop In the
      Clinic from these primary sources in collaboration with the ACP's Medical
      Education and Publishing division and with assistance of science writers and
      physician writers. Editorial consultants from PIER and MKSAP provide expert
      review of the content. Readers who are interested in these primary resources for
      more detail can consult www.acponline.org, http://pier.acponline.org, and other
      resources referenced within each issue of In the Clinic. The information
      contained herein should never be used as a substitute for clinical judgment. CME
      OBJECTIVE: To review strategies to evaluate and reduce perioperative risk.

PMID- 19581643
TI  - Failure to recognize newly identified aortic dilations in a health care system
      with an advanced electronic medical record.
AB  - BACKGROUND: Concern is growing about missed test results, but data assessing
      their effect on patient safety are limited. OBJECTIVE: To examine the frequency
      with which computed tomography (CT)-documented dilations of the abdominal aorta
      are accompanied by evidence in the electronic medical record (EMR) that a
      clinician recognized the abnormality. DESIGN: Retrospective cohort study.
      SETTING: 2 hospitals in the Veterans Affairs Health Care System. PATIENTS:
      Patients with new dilations of the abdominal aorta detected on CT performed in
      2003. MEASUREMENTS: Radiology report and EMR evidence that the radiologist
      notified the clinical service, aneurysm size, and interval between CT and EMR
      recognition. RESULTS: Computed tomography scans of 4112 patients were reviewed
      and 440 (11%) aortic dilations were identified, of which 91 were new findings.
      Radiologists directly notified clinical teams about 5 (5%) new dilations.
      Clinical teams did not record in the EMR recognition of 53 of 91 (58%) dilations
      within 3 months of the CT, and 9% of these dilations were 5.5 cm or larger. The
      median time to recognition of aneurysm in the EMR was 237 days, and no EMR
      documentation existed for 16 abnormalities (29% of surviving patients) during a
      mean follow-up of 3.2 years. No evidence indicated that any of the aneurysms
      ruptured or that patient deaths resulted from the delayed follow-up. LIMITATION:
      Clinicians may have recognized some aneurysms but did not document them in the
      EMR. CONCLUSION: Clinicians neglect to note a substantial proportion of new
      aortic dilations in the EMR. The findings highlight the need for better
      strategies to ensure documentation of follow-up of tests.

PMID- 19581644
TI  - Working conditions in primary care: physician reactions and care quality.
AB  - BACKGROUND: Adverse primary care work conditions could lead to a reduction in the
      primary care workforce and lower-quality patient care. OBJECTIVE: To assess the
      relationship among adverse primary care work conditions, adverse physician
      reactions (stress, burnout, and intent to leave), and patient care. DESIGN: Cross
      sectional analysis. SETTING: 119 ambulatory clinics in New York, New York, and in
      the upper Midwest. PARTICIPANTS: 422 family practitioners and general internists
      and 1795 of their adult patients with diabetes, hypertension, or heart failure.
      MEASUREMENTS: Physician perception of clinic workflow (time pressure and pace),
      work control, and organizational culture (assessed survey); physician
      satisfaction, stress, burnout, and intent to leave practice (assessed by survey);
      and health care quality and errors (assessed by chart audits). RESULTS: More than
      one half of the physicians (53.1%) reported time pressure during office visits,
      48.1% said their work pace was chaotic, 78.4% noted low control over their work,
      and 26.5% reported burnout. Adverse workflow (time pressure and chaotic
      environments), low work control, and unfavorable organizational culture were
      strongly associated with low physician satisfaction, high stress, burnout, and
      intent to leave. Some work conditions were associated with lower quality and more
      errors, but findings were inconsistent across work conditions and diagnoses. No
      association was found between adverse physician reactions, such as stress and
      burnout, and care quality or errors. LIMITATION: The analyses were cross
      sectional, the measures were self-reported, and the sample contained an average
      of 4 patients per physician. CONCLUSION: Adverse work conditions are associated
      with adverse physician reactions, but no consistent associations were found
      between adverse work conditions and the quality of patient care, and no
      associations were seen between adverse physician reactions and the quality of
      patient care.

PMID- 19581645
TI  - Screening for impaired visual acuity in older adults: U.S. Preventive Services
      Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 1996 U.S. Preventive Services Task Force (USPSTF)
      recommendation statement on screening for visual impairment. METHODS: The USPSTF
      reviewed evidence published since its last review on screening adults 65 years or
      older in the primary care setting for visual acuity impairment associated with
      uncorrected refractive errors, cataracts, and age-related macular degeneration.
      RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to
      assess the balance of benefits and harms of screening for visual acuity for the
      improvement of outcomes in older adults. (I statement).

PMID- 19581646
TI  - Screening older adults for impaired visual acuity: a review of the evidence for
      the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Impaired visual acuity is common in older adults. Screening for
      impaired visual acuity could lead to interventions to improve vision, function,
      and quality of life. PURPOSE: To update the 1996 U.S. Preventive Services Task
      Force evidence review on benefits and harms of screening for impaired visual
      acuity in primary care settings in adults age 65 years or older. DATA SOURCES:
      MEDLINE and the Cochrane Central Register of Controlled Trials and the Cochrane
      Database of Systematic Reviews were searched for studies published in English
      from 1996 to July 2008. STUDY SELECTION: Randomized trials and controlled
      observational studies that directly evaluated screening for impaired visual
      acuity in older adults were selected. To evaluate indirect evidence on screening,
      investigators included studies of diagnostic test accuracy and systematic
      reviews, randomized trials, and controlled observational studies of treatments
      for uncorrected refractive errors, cataracts, and age-related macular
      degeneration (AMD). DATA EXTRACTION: Details were abstracted about the patient
      sample, study design, data analysis, follow-up, and results. Quality was assessed
      by using predefined criteria. DATA SYNTHESIS: Direct evidence on screening and
      evidence on accuracy of diagnostic tests were synthesized qualitatively. For
      benefits and harms of treatments, quantitative estimates for treatment effects
      from good-quality systematic reviews were reported or relative risks using a
      random-effects model were calculated. Direct evidence shows that screening for
      vision impairment in older adults in primary care settings is not associated with
      improved visual or other clinical outcomes and may be associated with unintended
      harms, such as increased falls. Effective treatments are available for
      uncorrected refractive error, cataracts, and AMD. A visual acuity test (for
      example, the Snellen eye chart) is the standard for screening for vision
      impairment in primary care, but its diagnostic accuracy is uncertain because no
      studies compare it against a clinically relevant reference standard. There
      remains no evidence on accuracy of funduscopic examination. LIMITATIONS: A
      relatively small number of primary studies and methodological shortcomings made
      it difficult to reach conclusions with a high degree of confidence. In addition,
      studies not published in English and studies of community- or home-based
      screening were not included. CONCLUSION: More research is needed to understand
      why direct evidence shows no benefits of screening, even though impaired visual
      acuity is common and effective treatments are available.

PMID- 19581647
TI  - Angiotensin-receptor blockers in the prevention or treatment of microalbuminuria.

PMID- 19581648
TI  - The uncertain future of primary medical care.

PMID- 19581649
TI  - Medical journal editing: who shall pay?

PMID- 19581650
TI  - Do methodological flaws invalidate a randomized trial of lifestyle modification
      programs in obese patients?

PMID- 19581651
TI  - Additional factors that could improve cost-effectiveness of pharmacogenetic
      guided dosing in warfarin therapy.

PMID- 19581652
TI  - Hypothyroidism misdiagnosed as statin intolerance.

PMID- 19581653
TI  - The Netherlands Journal of Medicine: the next episode.

PMID- 19581654
TI  - Air pollution as noxious environmental factor in the development of
      cardiovascular disease.
AB  - A strong epidemiological association has been revealed between air pollution and
      the occurrence of cardiovascular disease (CVD). Deleterious consequences of such
      pollution, including myocardial infarction and coronary ischaemia, have occurred
      after both acute as well as chronic exposure to air pollution. The causal
      pathophysiological mechanisms through which these effects occur have not been
      identified but potential pathways include endothelial dysfunction and systemic
      reactions such as inflammation and oxidative stress. Because of increasing
      urbanisation and associated anthropogenic activities, air pollution is considered
      an important topic in public health and it remains challenging to translate these
      epidemiological observations into clinical consequences and guidelines.
      Nevertheless, for the high cardiovascular risk population, air pollution might
      have direct clinical relevance. In the future, more knowledge is required about
      the absolute risk of air pollution in specific high-risk populations and the
      pathophysiological mechanisms behind this relationship.

PMID- 19581655
TI  - The emergency care of cocaine intoxications.
AB  - Cocaine is frequently used, especially among adolescents and by men between the
      age of 25 and 44. Many of them are able to use cocaine in normal day-to-day life,
      without any problems. Reduced prices of cocaine and other recreational drugs such
      as MDMA (ecstasy) and gamma hydroxybutyrate (GHB) has led to an increased
      incidence of intoxications with these drugs. Since the production of cocaine is
      illegal, it may be impure and mixtures with other drugs such as atropine may
      occur. The treatment of patients with an acute cocaine intoxication can be
      complicated. Combination of cocaine with other drugs results in clinical pictures
      which are difficult to discriminate and that may have important consequences for
      treatment.

PMID- 19581656
TI  - Establishment of reference values for endocrine tests. Part VII: growth hormone
      deficiency.
AB  - BACKGROUND: Plasma insulin-like growth factor (IGF-I) concentration can be used
      as a rough indicator of the growth-hormone status. However, for the diagnosis of
      growth hormone deficiency, dynamic tests are required. The growth hormone (GH)
      response in the insulin tolerance test (ITT) is considered to be the gold
      standard in this respect. An alternative for the ITT is the GHRH/ GHRP-6 test,
      which has fewer side effects. In this study we established reference values for
      IGF-I levels and for the GH response in both dynamic tests. METHODS: We studied
      296 subjects recruited from the general population, equally distributed according
      to sex and aged between 20 and 70 years. Serum IGF-I level was measured in all
      subjects and an insulin tolerance test (0.15 U/kg Actrapid iv) and GHRH/GHRP-6
      test (1 microg GHRH/kg and 1 microg GHRP-6/kg) were performed in 49 subjects.
      RESULTS: In multivariate analyses both IGF-I and the GH response in the ITT were
      significantly influenced by age, whereas the GH response in the GHRH/GHRP-6 test
      was significantly affected by BMI. There was no sex difference in IGF-I and in
      the GHRH/GHRP-6 test, but in the ITT males had a higher GH peak. There was a
      significant correlation between the GH responses in both tests, and the GH
      response was significantly higher in the GHRH/GHRP-6 test than in the ITT. Age
      adjusted reference values were established for each test. CONCLUSION: We have
      established age-adjusted reference values for serum IGF-I and for the GH response
      in the ITT and GHRH/GHRP-6 test.

PMID- 19581657
TI  - No modification of the beneficial effect of NSAIDs on colorectal cancer by CYP2C9
      genotype.
AB  - BACKGROUND: CYP2C9 enzymes are involved in non-steroidal anti-inflammatory drug
      (NSAID) metabolism. Therefore, we investigated whether CYP2C9*2 and *3 variant
      alleles, encoding for enzymes with lower activity, increased the protective
      effect of NSAIDs on colorectal cancer. METHODS: Individual and combined
      associations of NSAIDs and CYP2C9*2 and *3 variant alleles with colorectal cancer
      were studied in 7757 Caucasian individuals of The Rotterdam Study, a population
      based prospective cohort since 1990. Additive and multiplicative effect
      modification models were used to examine drug-gene interactions. RESULTS: There
      were 212 incident cases of colorectal cancer during follow-up. A reduced risk of
      colorectal cancer was observed in individuals who used NSAIDs for more than a
      year (HR 0.45; 95% CI 0.28 to 0.71), and in carriers of an CYP2C9 variant allele
      associated with lower enzymatic activity (HR 0.67; 95% CI 0.47 to 0.96). The
      combination of both determinants was associated with a further risk reduction but
      without synergy. CONCLUSION: Both NSAID use and CYP2C9*2 and/ or *3 carriage are
      associated with a reduced risk of colorectal cancer. However, no interaction
      between the determinants was found, which might indicate independent
      pathophysiological mechanisms.

PMID- 19581658
TI  - Immunophenotyping of mast cells: a sensitive and specific diagnostic tool for
      systemic mastocytosis.
AB  - INTRODUCTION: The diagnosis of systemic mastocytosis (SM) is based on a
      combination of major and minor criteria. Flow cytometric detection of aberrant
      expression of CD2 and/or CD25 on CD117-positive mast cells is one of the minor
      criteria used. In the present study we examined the sensitivity and specificity
      of mast cell immunophenotyping in the diagnosis of SM. MATERIAL AND METHODS:
      Patients were 36 persons with SM diagnosed according to WHO criteria. Controls
      were 31 patients without SM. Immunophenotyping was performed according to
      published guidelines. RESULTS: All patients with SM were positive for CD2 and/or
      CD25. All patients without SM , except one, were negative for these markers. The
      sensitivity for immunophenotyping was 100%, the specificity 91%. The positive and
      negative predictive values were 97% and 100% respectively. CONCLUSION:
      Immunophenotyping of bone marrow derived mast cells is not only a very sensitive
      but also a very specific method to diagnose SM with high positive and negative
      predictive value.

PMID- 19581659
TI  - DRESS syndrome caused by nitrofurantoin.
AB  - Systemic side effects of nitrofurantoin are rare but can be life-threatening.
      Serious side effects are pulmonary involvement and Stevens-Johnson syndrome. We
      report a case of a patient developing circulatory and renal failure together with
      eosinophilia and a rash. This syndrome of drug rash, eosinophilia and systemic
      symptoms is called DRESS syndrome.

PMID- 19581660
TI  - Thyroid function in patients with proteinuria.

PMID- 19581661
TI  - A productive cough.

PMID- 19581662
TI  - Acute ischaemic limb.

PMID- 19581663
TI  - Cystic renal mass.

PMID- 19581664
TI  - Symptom experience, nonadherence and quality of life in adult liver transplant
      recipients.
AB  - Survival outcomes after liver transplantation in adult patients have gradually
      improved with a five-year survival of about 70% and a ten-year survival of about
      60%. The present review focuses on relevant patient-reported outcomes such as
      self-perceived side effects of immunosuppressive drugs, medication nonadherence
      and long-term health-related quality of life after liver transplantation. These
      entities are interrelated but have often been studied separately. Self-perceived
      symptom experience in liver transplant recipients has not been studied
      extensively. Symptoms that cause distress differ between men and women, e.g.
      symptoms related to cosmetic side effects of drugs. Medication nonadherence seems
      to be infrequent, but if present may have serious consequences. Important risk
      factors were found to be the costs of drugs, age <40 years, psychiatric
      disorders, side effects of drugs, beliefs that drugs were harmful, and large
      influence of the liver transplant on the patient's life. Health-related quality
      of life is satisfactory, but below the level of the general population. Results,
      however, must be interpreted with caution as quality-of-life improvements may
      have been overstated due to variables such as selection bias (e.g. exclusion of
      severely ill and deceased patients), too many short-term studies, and suboptimal
      methodology. Presently we lack data on the influence of recurrence of disease,
      'de novo' diseases and gender differences on health-related quality of life in
      liver transplanted patients.

PMID- 19581665
TI  - Hypomagnesaemia due to use of proton pump inhibitors--a review.
AB  - Magnesium homeostasis is essential for many intracellular processes and depends
      on the balance of intestinal absorption and renal excretion. Hypomagnesaemia may
      arise from various disorders. We review the literature on hypomagnesaemia due to
      the use of proton pump inhibitors, as illustrated by a case of a 76-year-old
      woman with muscle cramps and lethargy caused by hypomagnesaemia and hypocalcaemia
      with a low parathyroid hormone level while using esomeprazole, a proton pump
      inhibitor (PPI). After oral magnesium repletion both abnormalities resolved.
      Fractional magnesium excretion was low, excluding excessive renal loss. A causal
      relation with PPI use was supported by the recurrence of hypomagnesaemia after
      rechallenge. In the past decade our understanding of transcellular magnesium
      transport was enhanced by the discovery of several gene mutations i.e. transient
      receptor potential melastin (TR PM) 6 and 7. In this light we discuss the
      possible aetiology of proton pump inhibitor related hypomagnesaemia.

PMID- 19581666
TI  - Amoxicillin/clavulanate (Augmentin) resistant Escherichia coli in bacterial
      peritonitis after abdominal surgery--clinical outcome in ICU patients.
AB  - Bacterial resistance to antimicrobial agents is of great concern to clinicians.
      Patient outcome after infection is mainly dependent on the sensitivity of the
      bacterium to the agent used. We retrospectively studied 89 postoperative
      intensive care unit (ICU) patients with proven Escherichia coli peritonitis and
      investigated the clinical consequences of the E. coli resistance to
      amoxicillin/clavulanate. Significantly increased mortality, days of ventilation
      and ICU stay were noted in the co-amoxicillin/clavulanate resistant group.
      Furthermore, our results demonstrate that the sensitivity of E. coli to
      amoxicillin/clavulanate in the postoperative ICU setting has decreased in recent
      years. We can conclude that the current antibiotic regimen for the empirical
      treatment of ICU patients with peritonitis, as used in our hospital, needs to be
      changed. A switch, for instance, to ceftriaxone (Rocephin) in combination with
      metronidazole and gentamicin, instead of the present regimen of
      amoxicillin/clavulanate in combination with gentamicin, seems preferable.

PMID- 19581667
TI  - Current clinical care compared with new Dutch guidelines for hepatitis C
      treatment.
AB  - BACKGROUND: Recently, the Dutch Association of Gastroenterology and Hepatology
      issued new guidelines for the treatment of chronic hepatitis C virus (HCV). These
      guidelines reflect the current standard of care. Before these guidelines were
      published and implemented we (1) studied the current clinical care of HCV
      patients among Dutch physicians, and (2) identified areas for future refinement
      in the current treatment. METHODS: We conducted a non-targeted survey among Dutch
      medical specialists in Gastroenterology, Hepatology and Internal Medicine who
      actively treat HCV patients. The questionnaire contained items about facility,
      duration and dosing of treatment, and side effect management using clinical
      vignettes followed by short questions. RESULTS: We received 49 questionnaires
      from treating HCV specialists. The majority (65%) of respondents treat HCV
      patients during regular outpatient clinics, while 35% treat these patients in a
      separate setting dedicated to the care of HCV patients. The majority of
      physicians follow the stipulated dosage regimens of pegylated interferon (88%)
      and ribavirin (83%). A minority (13%) exceed the advised dosage of ribavirin.
      Side effects such as neutropenia are mostly managed by decreasing the interferon
      dosage (42%). Some 35% of physicians reduce ribavirin if haemoglobin levels drop
      below 5.4 mmol/l, and 41% initiate erythropoietin treatment. CONCLUSION: Dutch
      clinical practice reflects the recently issued HCV guidelines. An important area
      of refinement in treatment of HCV is the management of side effects.

PMID- 19581668
TI  - Earlier stages of colorectal cancer detected with immunochemical faecal occult
      blood tests.
AB  - BACKGROUND: The aim of colorectal cancer screening is to improve prognosis by the
      detection of early cancer and precursor stages. We compared the stage
      distribution of asymptomatic colorectal cancer patients detected by a positive
      immunochemical or guaiac-based faecal occult blood test (FOBT) with symptomatic
      colorectal cancer patients. METHODS: In a longitudinal cohort study tumour stages
      were assessed in 144 symptomatic (mean age 69.3 years, 56% male) and 41
      asymptomatic colorectal cancer patients (mean age 64.9 years, 56% male) of which
      11 were detected with guaiac FOBT s (G-FOBT, Hemoccult-II) and 30 with
      immunochemical FOBTs (I-FOBT, OCSensor). Stage distributions were used to
      calculate average stage specific predicted five-year survival rates and to
      analyse group differences with Wilcoxon log-rank test. RESULTS: Colorectal cancer
      was detected in significantly earlier stages in symptomatic compared with
      asymptomatic patients patients (p<0.0001). Average stage specific predicted five
      year survival was 59.1% in symptomatic and 76.6% in asymptomatic patients.
      Compared with the symptomatic patients the stage distribution for colorectal
      cancer patients detected with Hemoccult-II was not significantly
      different(p=0.29), whereas colorectal cancer was detected at significantly
      earlier stages with the OCSensor (p<0.0001).Treatment could be confined to
      colonoscopy in 27% of the asymptomatic patients compared with 3% of the
      symptomatic patients (p<0.0001). Cancer distribution over the colon was
      comparable between symptomatic and asymptomatic patients (p=0.3). CONCLUSIONS:
      Compared with symptomatic patients,patients detected by FOBT and especially
      immunochemical FOBT , presented significantly more often at earlier stages
      suggesting increased survival. Additionally treatment could more often be
      confined to colonoscopy.

PMID- 19581669
TI  - Food-dependent Cushing's syndrome.
AB  - It has recently been proposed that other hormones than ACTH can control cortisol
      production in Cushing's syndrome with bilateral adrenal hyperplasia. We present a
      case of food-dependent Cushing's syndrome. After a positive response of cortisol
      production during mixed meals, several tests identified glucose-dependent
      insulinotropic polypeptide (GIP) as the driving hormone responsible for the
      cortisol overproduction. Identification of aberrant hormone receptor expression
      is of importance because it may create a possibility for pharmacological
      treatment.

PMID- 19581670
TI  - Granulocytosis and thrombocytosis in renal cell carcinoma: a pro-inflammatory
      cytokine response originating in the tumour.
AB  - BACKGROUND: In up to 20% of patients with renal cell cancer (RCC) an inflammatory
      response consisting of low-grade fever, weight loss and an elevated ESR and CRP
      may occur with modest granulocytosis and thrombocytosis. Clinical and
      experimental data suggest a pathogenic role for tumour-derived cytokine
      production, especially interleukin-6. CASE REPORT: A 79-year-old female with RCC
      presented with low-grade fever, weight loss and overt granulocytosis and
      thrombocytosis. Radiological examination revealed a right-sided renal tumour.
      During nephrectomy a gradient between the IL-6 levels in the renal artery and
      vein was demonstrated, providing direct evidence for in vivo production of IL-6
      by the tumour affected kidney, which was confirmed by the demonstration of IL -6
      in the tumour cells by immunohistochemical staining and in the supernatant of the
      homogenised tumour. Cytogenetic examination revealed complex abnormalities
      including a gain of chromosome 7. In addition we demonstrated production of IL
      1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of
      IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels. CONCLUSION: We
      have provided direct evidence for the production of pro-inflammatory cytokines by
      renal cancer cells in a patient with RCC and a profound inflammatory response,
      with a central role of IL-6, probably due to a gain of chromosome 7. The extreme
      granulocytosis and thrombocytosis may have resulted from the secondary systemic
      production of G-CSF and TPO.

PMID- 19581671
TI  - Diagnosis of Wilson's disease.

PMID- 19581673
TI  - Severe and symptomatic hyponatraemia after moxifloxacin intake.

PMID- 19581674
TI  - A well-circumscribed density along the right heart border. Pericardial cysts.

PMID- 19581675
TI  - Bullous dermatosis. Bullous pemphigoid.

PMID- 19581676
TI  - A young man with progressive dysphagia. Eosinophilic esophagitis.

PMID- 19581689
TI  - The fabrication of a carbon nanotube array using a catalyst-poisoning layer in
      the inverse nano-sphere lithography method.
AB  - A new method for the fabrication of periodic CNT arrays was developed in this
      study, which involves the use of the inverse nano-sphere lithography (INSL)
      process. Mo of a honeycomb pattern, acting as a catalyst-poisoning layer, was
      produced by the nano-sphere lithography (NSL) process; the Mo poisoned the
      catalyst and prevented CNT growth where deposited, and as a result, a periodic
      CNT pattern was obtained. Using this method, the uniformity of the CNT array can
      be improved by preventing the negative effect of arrangement defects in self
      assembled monolayers. The size and the period of the CNT array can be adjusted by
      careful selection of the polystyrene (PS) sphere diameter. X-ray photoelectron
      spectroscope (XPS) analysis revealed that the Co catalyst was ineffective on the
      areas of Mo deposition due to the diffusion of Co into the Mo layer.

PMID- 19581690
TI  - Studies on CuTAPc-nanotube-modified electrodes as chemical sensors for NO.
AB  - Poly-copper tetraaminophthalocyanine (CuTAPc) nanotubes were successfully
      fabricated on porous alumina templates by electropolymerization. Their high
      surface area and simple preparation protocol made them potential candidates as
      the modification layer of electrodes for sensor application. High sensitivities
      and improved linear ranges were obtained through different measurements such as
      differential pulse voltammetry (DPV), differential potential amperometric (DPA)
      and electrochemical impedance spectroscopy (EIS). Detection limits as low as 10
      nM were demonstrated in common voltammetric analysis with ultra-high response
      current in the microA range.

PMID- 19581691
TI  - Interfacial energy levels and related properties of atomic-layer-deposited Al2O3
      films on nanoporous TiO2 electrodes of dye-sensitized solar cells.
AB  - Low-temperature (approximately 150 degrees C), atomic-layer-deposited Al(2)O(3)
      films on nanoporous TiO2 electrodes of dye-sensitized solar cells (DSSCs) were
      investigated using electron spectroscopy. The power conversion efficiency (PCE)
      of the DSSCs was increased from 5.7% to 6.5%, an improvement of 14%, with one
      monolayer of Al(2)O(3) with a thickness of approximately 0.2 nm. The formation of
      Ti-O-Al(OH)(2) and interfacial dipole layers exhibited a strong influence on the
      work function of the Al(2)O(3) over-layers, while the thicker Al(2)O(3) over
      layers caused the values of valence band maximum and band gap to approach the
      values associated with pure Al(2)O(3). A work function difference (Delta Phi(A
      T)) of 0.4 eV and a recombination barrier height (epsilon(RB)) of 0.1 eV were
      associated with the highest PCE achieved by the first monolayer of the Al(2)O(3)
      layer. Thicker Al(2)O(3) over-layers, however, caused significant reduction of
      PCE with negative Delta Phi(T-A) and increased interfacial energy barrier height
      ((*)epsilon(IB)) between the N719 dyes and TiO2 electrodes. It was concluded that
      the PCE of the DSSCs may correlate with Delta Phi(A-T), epsilon(RB), and
      (*)epsilon(IB) resulting from various thicknesses of the Al(2)O(3) over-layers
      and that interfacial reactions, such as the formation of Ti-O-Al(OH)(2) and
      dipole layers, play an important role in determining the interfacial energy
      levels required to achieve optimal performance of dye-sensitized TiO2 solar
      cells.

PMID- 19581693
TI  - Transition flow through an ultra-thin nanosieve.
AB  - The fabrication and gas flow characterization of an ultra-thin inorganic
      nanosieve structured by interference lithography and a bond-micromachining
      approach are reported. The nanosieve has been observed to exhibit transition gas
      flow behaviour around atmospheric pressure and ambient temperature. The small lip
      thickness (45 nm) of the nanopores with respect to their diameter (120 nm) helps
      in understanding pure transition flow by minimizing interactions between the
      molecule and inner pore wall. Due to the absence of these collisions, the
      transition flux is the superimposition of viscous and molecular fluxes without
      the need for higher-order slip correction. The nanosieve shows a flow selectivity
      of 3.1 between helium and argon at 20 mbar.

PMID- 19581692
TI  - Increased endothelial cell adhesion and elongation on micron-patterned nano-rough
      poly(dimethylsiloxane) films.
AB  - The success of synthetic vascular grafts is largely determined by their ability
      to promote vital endothelial cell functions such as adhesion, alignment,
      proliferation, and extracellular matrix (ECM) deposition. Developing such
      biomaterials requires the design and fabrication of materials that mimic select
      properties of native extracellular matrices. Furthermore, cells of the native
      endothelium have elongated and aligned morphology in the direction of blood flow,
      yet few materials promote this type of morphology initially, but rather rely on
      blood flow to orient endothelial cells. Therefore, the objective of this in vitro
      study was to design a biomaterial that mimics the conditions of the micro- and
      nano-environment of vascular intima tissue suitable for endothelial cell adhesion
      and elongation to improve the efficacy of small synthetic vascular grafts.
      Towards this end, patterned poly(dimethylsiloxane) (PDMS) films consisting of
      periodic arrays of nano-grooves (500 nm), with spacings ranging from 22 to 80
      microm, and alternating nano- and micron roughness were fabricated using a novel
      electron beam physical vapor deposition method followed by polymer casting. By
      varying pattern spacing, the area of micron- and nano-rough surface was
      controlled. In vitro rat aortic endothelial cell adhesion and elongation studies
      indicated that endothelial cell function was enhanced on patterned PDMS surfaces
      with the widest spacing and greatest surface area of nano-roughness, as compared
      to more narrow pattern spacings and non-patterned PDMS surfaces. Specifically,
      endothelial cells adherent on PDMS patterned films of the widest spacing
      (greatest nano-rough area) displayed almost twice as much elongation as cells on
      non-patterned surfaces. For these reasons, the present study highlighted design
      criteria (the use of micron patterns of nano-features on PDMS) that may
      contribute to the intelligent design of new-generation vascular grafts.

PMID- 19581694
TI  - Observation of localized surface plasmons in spatially controlled array
      structures.
AB  - We observed the reflectance spectra of three different nano-scale array
      structures of Au-coated silicon nanorods. The trends of the reflectance spectra
      indicate that the localized surface plasmon modes can be spatially controlled by
      manipulating geometric parameters, namely the lattice constants of the array. In
      addition, the experimental results were compared with 2D numerical simulations
      based on the finite element method. Satisfactory agreement between the
      experimental observations and numerical results was obtained.

PMID- 19581695
TI  - Compact quantum dot probes for rapid and sensitive DNA detection using highly
      efficient fluorescence resonant energy transfer.
AB  - We developed a simple method for quickly synthesizing compact quantum dot (QD)
      DNA probes for sensitive DNA detection using fluorescence resonant energy
      transfer (FRET). The density of DNA probes on the QD surface was controlled to
      avoid steric hindrance and to promote rapid hybridization with target DNA
      molecules. The radius of the final QDs was only around 3 nm after applying the
      functional coating, enabling highly efficient energy transfer. It was
      demonstrated that nearly 70% transfer efficiency could be achieved with only a
      few DNA molecules on each QD and that the FRET-based DNA detection could be
      carried out within 10 min with a sub-nM detection limit. Theoretical analysis was
      also performed to confirm our results.

PMID- 19581696
TI  - Anodic fabrication and bioactivity of Nb-doped TiO2 nanotubes.
AB  - We report anodic formation of Ti-Nb-O nanotubes on top of a Ti35Nb alloy, and in
      vitro bioactivity and stem cell response of the anodic nanotubes. It was found
      that the amorphous Ti-Nb-O nanotubes presented a significantly enhanced in vitro
      bioactivity (in simulated body fluids) compared to those of undoped TiO2
      nanotubes and porous Ti-Nb-O without nanotubular structure. Similar to undoped
      TiO2 nanotubes, the Ti-Nb-O nanotubes also promote mesenchymal stem cell adhesion
      and fast formation of extracellular matrix (ECM) materials. The above findings
      make it possible to further explore the biological properties, such as cell
      proliferation and drug delivery, of a variety of Ti-alloy-based oxide nanotubes.

PMID- 19581697
TI  - A rapid hydrothermal synthesis of rare earth oxide activated Y (OH)3 and Y2O3
      nanotubes.
AB  - One-dimensional single crystalline rare earth ion (Tm(3+), Tb(+3), and Eu(3+))
      doped Y (OH)(3) nanotubes with inner diameters of 20-110 nm, outer diameters of
      50-140 nm, and 1-5 microm in length were prepared for the first time by a rapid
      hydrothermal method within a short reaction period (5 min) at subcritical
      temperature (320 degrees C) and high pressure (about 40 MPa). A temperature
      dependent nanostructure evolution study was performed under rapid hydrothermal
      conditions and the effects of other processing parameters such as concentration
      of KOH and reaction time were found to be key parameters for the formation of
      highly anisotropic crystal structures of rare earth hydroxide nanotubes. Rare
      earth ion (Tm(3+), Tb(+3), and Eu(3+)) doped Y(2)O(3) nanotubes can be obtained
      after calcinations above 450 degrees C. The luminescent property of rare earth
      doped Y(2)O(3) nanotubes was also explored and compared with reference samples
      prepared via a conventional co-precipitation method.

PMID- 19581698
TI  - Thermoresponsive core-shell magnetic nanoparticles for combined modalities of
      cancer therapy.
AB  - Thermoresponsive polymer-coated magnetic nanoparticles loaded with anti-cancer
      drugs are of considerable interest for novel multi-modal cancer therapies. Such
      nanoparticles can be used for magnetic drug targeting followed by simultaneous
      hyperthermia and drug release. Gamma-Fe(2)O(3) iron oxide magnetic nanoparticles
      (MNP) with average sizes of 14, 19 and 43 nm were synthesized by high temperature
      decomposition. Composite magnetic nanoparticles (CNP) of 43 nm MNP coated with
      the thermoresponsive polymer poly-n-isopropylacrylamide (PNIPAM) were prepared by
      dispersion polymerization of n-isopropylacrylamide monomer in the presence of the
      MNP. In vitro drug release of doxorubicin-(dox) loaded dehydrated CNP at
      temperatures below and above the lower critical solution temperature of PNIPAM
      (34 degrees C) revealed a weak dependence of drug release on swelling behavior.
      The particles displayed Fickian diffusion release kinetics; the maximum dox
      release at 42 degrees C after 101 h was 41%. In vitro simultaneous hyperthermia
      and drug release of therapeutically relevant quantities of dox was achieved,
      14.7% of loaded dox was released in 47 min at hyperthermia temperatures. In vivo
      magnetic targeting of dox-loaded CNP to hepatocellular carcinoma (HCC) in a
      buffalo rat model was studied by magnetic resonance imaging (MRI) and histology.
      In summary, the good in vitro and in vivo performance of the doxorubicin-loaded
      thermoresponsive polymer-coated magnetic nanoparticles suggests considerable
      promise for applications in multi-modal treatment of cancer.

PMID- 19581699
TI  - High quality InAs quantum dots grown on patterned Si with a GaAs buffer layer.
AB  - Ordered and dense InAs quantum dots grown on patterned Si(100) with a thin GaAs
      buffer layer have been investigated by transmission electron microscopy and
      electron energy loss spectroscopy. {111} faceted InAs quantum dots with good
      crystallinity were observed on top of the underlying GaAs buffer layer. It was
      revealed that the GaAs buffer layer and the lateral expansion of InAs have played
      key roles in releasing the misfit strain between InAs and Si and suppressing the
      formation of lattice defects in InAs quantum dots. These results suggest a
      possible pathway for the strain relaxation in the formation of quantum dots.

PMID- 19581700
TI  - Polymer physics of the cell. Preface.

PMID- 19581701
TI  - Studies of Paramecium caudatum by means of scanning electron microscope and
      projection X-ray microscope.
AB  - Samples of Paramecium caudatum are observed by means of a scanning electron
      microscope (SEM) and a projection X-ray microscope (XRM) with computer tomography
      (CT) function. The samples are fixed with two kinds of fixatives, glutaraldehyde
      and osmium-tetra oxide acid. After the fixation and replacement procedure with t
      buthyl alcohol, the samples followed by a freeze drying, well retain their
      structures. Surface structures, cilia and microfibrillar systems including
      infraciliary lattice structures, are clearly depicted by SEM observation. On the
      other hand, XRM images give quite different information, namely, in the case of
      osmium oxide fixation, the structures of internal organelles like the
      macronucleus placed in the central part of cell body and trichocysts located
      under the cell membrane of a whole body are visible. In the case of
      glutaraldehyde fixation, the surface structures and internal structures are both
      visible but their image contrast is fairly weak. In order to examine
      toxicological effect, Paramecium caudatum samples treated in the environmental
      condition containing nano-particles of Ag (17 nm across) and Co-ferrite (300 nm
      across) are observed with results of certain morphological differences, namely,
      inner vacuoles increase in number and in volume in Co-ferrite treated cells as
      compared with Ag treated ones. But then, cilia-less areas increase on the surface
      of the body of Ag treated cells. In the case of Co-ferrite treated cells, cilia
      less areas are not clearly detected. Whether these morphological differences
      observed in Ag and Co-ferrite treated cells are caused by the differences of
      materials or particle sizes remain to be examined in future.

PMID- 19581702
TI  - Low-voltage and high-voltage TEM observations on MWCNTs of rat in vivo.
AB  - In the present study, we focused on the optimal conditions for observation of
      morphology and atomic structure of carbon nanotube (CNT) in vivo by transmission
      electron microscopy (TEM). Either low-voltage or high-voltage TEMs was chosen for
      the high-contrast or high-resolution imaging of subcutaneous tissue and the multi
      wall CNT (MWCNT). The morphology and structure of each cell organelle were well
      recognized using the low-voltage TEM at 75 kV. Individual MWCNTs forming the
      cluster were also visible by the low-voltage TEM. On the contrary, the high
      voltage TEM image at 1250 kV shows poor contrast on both the cell organelles and
      MWCNTs. However, graphene layers of MWCNT were clearly visible in the HRTEM image
      using the high-voltage TEM. The influence of the surrounding biological tissue
      can be disregarded by the high-energy electrons due to their weak
      scattering/absorption effect in the tissue. It was indicated that the usage of
      the high-voltage TEM is quite effective to the atomic structure analysis of nano
      crystalline materials in vivo.

PMID- 19581703
TI  - Development of a second-generation radiofrequency ablation using sintered
      MgFe(2)O(4) needles and alternating magnetic field for human cancer therapy.
AB  - Magnetic metal particles are known to induce heat energy under an alternating
      magnetic field (AMF). We developed a local tumor-heating device incorporating an
      MgFe(2)O(4) needle for the purpose of mild ablation for cancer treatment. A
      needle made from sintered MgFe(2)O(4) particles was embedded in the hepatic or
      breast tumors. Tumors were then heated by the energy dissipated from the needle
      exposed to an AMF. We sequentially evaluated histological changes, cellular
      activity of tumors, and the extent of thermal effect using nicotinamide adenine
      dinucleotide (NADH) diaphorase and terminal deoxynucleotidyl tranferase-mediated
      digoxigenin-DUTP nick-end labeling (TUNEL) staining. The mean temperature of the
      tumor tissue during heating was about 60 degrees C. Nuclei of the tumor cells
      became hyper-chromatin immediately after heating. The injured area spread
      progressively until 3 days after heating; when the area was surrounded by
      fibroblasts (meaning is not clear). Tumors disappeared after treatment without
      complications. This is the first time that the complete death of tumor cells has
      been realized by raising the tumor temperature above 60 degrees C using the heat
      generated by magnetic metal particles exposed to AMF. This device may be useful
      in the future for local hyperthemic treatment of human cancers.

PMID- 19581704
TI  - Poly-L-arginine-hydroxyapatite nanoparticle complexes translocate through lipid
      bilayer membranes.
AB  - Certain molecules, which are able to directly translocate across phospholipid
      bilayer membranes (cell or endosormal membrane), can be useful as carriers
      (vectors) for drags (especially polymeric drags). We have studied the
      translocationability of the hydroxyapatite nanoparticle-poly-L-arginine complex
      through the negatively charged phospholipid bilayer membranes by using several
      instruments. It was confirmed by means of a confocal laser scanning microscopy
      (CLSM) not only the fact that the complex can translocate through the membranes
      but also the fact that the complexes were still retained in the inner water layer
      of the liposome even after the translocation.

PMID- 19581705
TI  - Development of a novel cement by conversion of hopeite in set zinc phosphate
      cement into biocompatible apatite.
AB  - Synthetic bone cement that has zinc oxide core particles covered with
      hydroxyapatite (HAP) was developed; that is, the conversion of hopeite, the
      traditional zinc phosphate cement, into HAP was attempted. Here, hopeite is the
      final product of the reaction between powders and trituration liquid of the
      traditional zinc phosphate cement. This cement may have many advantages not only
      in terms of biological functions but also the setting process of the traditional
      cement and the mechanical properties of the developed compact if the hopeite can
      be converted into calcium phosphate (CP). In this study, calcium nitrate
      solutions of various concentrations were used for the conversion of hopeite
      crystals into CP. The products after the solution treatment were analyzed by X
      ray diffractometry (XRD), Fourier transform infrared spectrometry (FTIR), and
      scanning electron microscope (SEM) observation. These results indicated that the
      converted scholzite crystals could be partially detected. Several types of set
      zinc phosphate cement with different P/L ratios were arranged. The surface
      products of the set cement after the solution treatment were analyzed by XRD.
      However, the crystal phase such as hopeite was not detected except for zinc
      oxide. The set cement, which was treated with the calcium nitrate solution, was
      immersed in simulated body fluid (SBF). HAP-like crystals on the set cement could
      be detected for the specimens immersed for 4 weeks. These findings suggested that
      the binding phase in the set cement could be converted into HAP by immersion in
      SBF.

PMID- 19581706
TI  - Fabrication of porous chitosan/hydroxyapatite nanocomposites: their mechanical
      and biological properties.
AB  - We fabricated novel chitosan/hydroxyapatite (HAp) nanocomposites with porous
      structure by the co-precipitation and porogen leaching method. SEM observation
      confirmed that the porous chitosan/HAp nanocomposites with 60.6% and 87.1%
      porosity showed the interconnective pores with pore diameters in the range of 100
      200 mum. The composites were found to be mechanically flexible and could be
      easily formed into any desired shape. The mechanical strength was enhanced by the
      heat treatment with saturated steam, which was ascribed to the formation of
      hydrogen bonds between chitosan molecules. The composites subcutaneously
      implanted in the backs of SD rats for 3 weeks caused little inflammation, and new
      blood vessel growth and giant cells were found around the composite accompanied
      with roughening of the surface due to degradation, showing good biocompatibility
      and biodegradation.

PMID- 19581707
TI  - BMP-2 release and dose-response studies in hydroxyapatite and beta-tricalcium
      phosphate.
AB  - The purpose of this study is to compare in vivo retention of BMP-2 and bone
      induction in HAp (porosity: 60-80%, pore size: 100-600 mum, sintering
      temperature: 800 degrees C, surface area: 1 m(2)/g) and beta-TCP (porosity: 75%,
      pore size: 100-400 mum, sintering temperature: 1050 degrees C, surface area: 4
      m(2)/g). We estimated the in vivo release profile of (125)I-labeled BMP-2 and
      bone induction of hard tissues histologically. The amount of BMP-2 remaining in
      the beta-TCP at 1 day after implantation was 49.6%, while the amount was 34.0% in
      the HAp. Furthermore, the HAp and beta-TCP containing 0.0, 0.05, 0.1, 0.3, 0.5,
      1.0, 5.0 microg of BMP-2 were implanted into the back subcutis of 4-week old
      Wistar rats. At 3 weeks after implantation, the ceramics were explanted and
      evaluated histologically. The HAp/BMP-2 (5.0 microg) system showed 3.0% in the
      total volume of bone at 3 weeks, while only in the beta-TCP/BMP-2 (5.0 microg)
      system showed 32.5%. These results indicate that the absorbable beta-TCP block
      may be an effective bioceramic for bone induction to deliver BMP-2 to the site of
      action.

PMID- 19581708
TI  - Adhesion of human osteoblast-like cells (Saos-2) to carbon nanotube sheets.
AB  - Carbon nanotubes (CNTs) exhibit excellent cell proliferation properties, which
      can serve as a scaffold for cell culturing. However, there are only a few reports
      on adhesion of osteoblast-like cells to a CNT sheet. In this study, we
      investigated adhesion of osteoblast-like cells to single-walled carbon nanotube
      (SWNT) and multi-walled carbon nanotube (MWNT) sheets and compared these
      adhesions with that on a cell culture polystyrene dish by using a cell adhesion
      test and a scanning electron microscope. The MWNT sheets exhibited faster
      adhesion of cells at an initial stage than SWNT sheets and cell culture
      polystyrene dish. The number of attached cells on the MWNT sheets seemed to be
      greater than on SWNT sheets and cell culture polystyrene. Moreover, the MWNT
      sheets exhibited both high speed and good capacity for cell adhesion. However,
      the surface of the MWNT sheets was such that it facilitated cell adherence but
      hindered the spreading of the attached cells. Interestingly, cell adhesion to CNT
      sheets was significantly influenced by pre-coating with serum. These results
      indicate that CNT sheets would play an important role in adsorption of serum
      proteins, which would consequently facilitate cell adhesion, and that the MWNT
      sheets have a high cell adhesiveness.

PMID- 19581709
TI  - Improvement in cell proliferation on silicone rubber by carbon nanotube coating.
AB  - Silicone rubbers are widely used as tissue implants because of their flexibility
      and chemical stability. However, they have limited cellular adhesiveness and may
      cause problems in the long term. In this study, a coating of carbon nanotubes
      (CNTs) was applied to silicone rubber to improve its cellular adhesiveness.
      Scanning electron micrograph of this coating revealed that CNTs had formed a
      densely packed meshwork; the Ra values and protein adsorption capacity were
      enhanced. Although the contact angle did not change after coating, it decreased
      after immersion into a culture medium. After cultivation for 6 d, while Saos-2
      cells were hardly observed on untreated silicone, the cells proliferated on CNT
      coated silicone. Thus, CNT coating might be a simple and effective solution to
      problems associated with silicone implants.

PMID- 19581710
TI  - Assessment of the nanostructure of acid-base resistant zone by the application of
      all-in-one adhesive systems: Super dentin formation.
AB  - An acid-base resistant zone (ABRZ) has been shown to be created under a hybrid
      layer in a self-etching adhesive system at the adhesive/dentin interface. The
      purpose of this study was to assess the nanostructure of the ABRZ by applying all
      in-one adhesive systems. Human premolar dentin was treated with one of two all-in
      one adhesive systems; Clearfil Tri-S Bond and G-Bond according to the
      manufacturers' instructions. After placement of a resin composite, the bonded
      interface was vertically sectioned and subjected to an acid-base challenge.
      Following this, the nanostructure of the ABRZ was examined by SEM and TEM. The
      SEM observations of the adhesive-dentin interface after the acid-base challenge
      indicated that a hybrid layer less than 1 mum thick was created, and a ABRZ was
      formed beneath the hybrid layer for each adhesive system. The TEM observations
      indicated that the ABRZ contained mineral components in both adhesive systems,
      however, the thickness of the ABRZ was material dependent. The application of the
      all-in-one adhesive systems created an ABRZ at the underlying dentin, which
      reinforced normal dentin against dental caries. Therefore, this zone was named
      'Super Dentin'. Formation of 'Super Dentin' is a new approach in caries
      prevention.

PMID- 19581711
TI  - A novel prosthetic resin composite containing fine enamel particles.
AB  - Finely powdered enamel was used to develop a prosthetic resin composite that has
      good mechanical properties and no potential to abrade opposing tooth structure.
      Bovine teeth were ground into powder and then the enamel particles were separated
      from the powder by centrifugation in bromoform-ethanol solution. The resin matrix
      consisted of UDMA (60 mole %) and Tri-EDMA (40 mole %). Camphorquinone (0.5 mass
      %) was added to the monomer as a photo-initiator. Fillers were incorporated
      directly into the resin matrix in amounts of 80 or 85 mass %. The flexural
      strength and Vickers hardness (Hv) were measured. The average flexural strength
      and Hv values for specimens having 85 mass % filler that had been subjected to
      heat treatment at 100 degrees C after light-curing were 95.2 and 109.8 MPa,
      respectively, which are higher than those for most commercial prosthetic resin
      composites. These findings suggest that a novel prosthetic resin composite with
      good mechanical properties can be made by loading finely powdered enamel into the
      resin matrix.

PMID- 19581712
TI  - Modification of the dentin surface by using carbon nanotubes.
AB  - Recent studies have shown that carbon nanotubes (CNTs) can be used as biomedical
      materials because of their unique properties. CNTs effect nucleation of
      hydroxyapatite, because of which considerable interest has been generated
      regarding the use of CNTs in dentistry. However, there are only a few reports on
      the use of CNTs as dental materials. In this study, we investigated the changes
      induced in the surfaces of tooth slices by the application of a coating of CNTs
      by observing CNT-coated tooth slices both macroscopically as well as under a
      scanning electron microscope. Further, we investigated the effect of CNT coating
      on the tensile bond strength of dentin adhesives. CNTs adhered easily to the
      tooth surfaces when tooth slices were suspended in a CNT-dispersed solution.
      Interestingly, it was observed that CNTs selectively adhered to the surfaces of
      dentin and cementum, possibly by adhering to their exposed collagen fibers. In
      addition, the CNT coating did not affect the tensile bond strength of dentin
      adhesives. These results indicate that coating of the teeth with CNTs can be a
      possible application of CNTs as dental materials.

PMID- 19581713
TI  - Formaldehyde reduction with scallop shell powders fired at high temperatures:
      Identification of the effective ingredient.
AB  - The volatile organic compound (VOC) reduction activity of scallop shell powders
      fired at 300, 600 and 900 degrees C was examined using formaldehyde (HCHO). Raw
      shells as well as fired shells immediately after firing at several temperatures,
      except for 600 degrees C, were found to gradually remove HCHO from the air. In
      the case of shell powders stored for 3 months after firing, the HCHO reduction
      activity of the powder fired at 900 degrees C was obviously improved, with the
      HCHO concentrations rapidly reaching zero within 20 min. It has been found by X
      ray diffraction measurements that shell powder stored for 3 months after firing
      at 900 degrees C contains a small amount of calcium hydroxide (Ca(OH)2) generated
      from calcium oxide (CaO). Our results suggest that Ca(OH)2 may be the effective
      ingredient in the HCHO reduction.

PMID- 19581714
TI  - Effects of heat treatment on the bioactivity of surface-modified titanium in
      calcium solution.
AB  - The purpose of this study was to determine the effects of heat treatment on the
      bioactivity of hydrothermal-modified titanium in CaO solution for improved
      bioactivity by immersion in simulated body fluid (SBF). The hydrothermal
      treatment of titanium in CaO solution was performed at 121 degrees C at 0.2 MPa
      for 1 h in an autoclave followed by 1 h heat treatments at 200, 400, 600 and 800
      degrees C simultaneously. The bioactivity of titanium was evaluated by
      hydroxyapatite precipitation during immersion in SBF. Surface microstructure
      changes after the heat treatments and immersion in SBF were determined by X-ray
      diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and scanning
      electron microscopy (SEM). Heat treatments at high temperatures (600 and 800
      degrees C) promoted the synthesis of anatase, increased the thickness of the
      titanium oxide layer on the modified titanium surface and promoted the synthesis
      of calcium titanate, which possibly promoted the precipitation of apatite in SBF.
      The extent of precipitations increased with the time of immersion in SBF and the
      temperature of the heat treatment. Island-like deposits of needle-like crystals
      were observed only on the surface of the 600 and 800 degrees C heat-treated
      specimens after two or four week immersions in SBF. The results suggested that
      treatments of the surface of hydrothermal-treated titanium specimens at high
      temperatures (600 and 800 degrees C) could be effective for the surface
      modification of titanium as an implant material offering better osseointegration.

PMID- 19581715
TI  - Effect of temperature on crystallinity of carbonate apatite foam prepared from
      alpha-tricalcium phosphate by hydrothermal treatment.
AB  - The effect of temperature on crystallinity of carbonate apatite (CAp) foam
      prepared from alpha-tricalcium phosphate (alpha-TCP) foam by hydrothermal
      treatment was investigated in the present study. The alpha-TCP foams were
      prepared through a conventional sintering method using polyurethane foam as
      template. Then, the resultant alpha-TCP foams were hydrothermally treated with
      Na2CO3 aqueous solution at 100 degrees C, 150 degrees C and 200 degrees C for 72
      h. After hydrothermal treatment, the cancellous bone-like macroporous structure
      of the alpha-TCP foams was maintained. However, microscopic morphology of the
      foams' frame significantly changed after the 72 h treatment period. The smooth
      surface of alpha-TCP foam disappeared and the whole surface was covered with
      plate-like deposits. The plate-like deposits treated at 150 degrees C and 200
      degrees C had smooth surface while those treated at 100 degrees C were
      constructed from spherical particles of approximately 200 nm in diameter. The
      results of X-ray diffraction and Fourier transform infrared analysis showed that
      alpha-TCP was completely converted to CAp and the crystallinity of CAp prepared
      at 100 degrees C was significantly lower than those prepared at 150 degrees C and
      200 degrees C. Hydrothermal treatment of alpha-TCP foam at 100 degrees C allowed
      the formation of low-crystalline CAp foam but complete conversion needs a longer
      treatment period.

PMID- 19581716
TI  - Biodistribution imaging of magnetic particles in mice: X-ray scanning analytical
      microscopy and magnetic resonance imaging.
AB  - Nano-sized particles have received much attention in view of their varied
      application in a wide range of fields. For example, magnetite (Fe(3)O(4))
      nanoparticles have been investigated for various medical applications. In this
      study, we visualized the distribution of administered magnetic nanoparticles in
      mice using both X-ray scanning analytical microscopy (XSAM) and magnetic
      resonance imaging (MRI). After administration, the nanoparticles were rapidly
      dispersed via the blood circulation, and reached the liver, kidney and spleen.
      Using the XSAM and MRI methods in a complementary fashion, the biodistribution of
      nano-sized magnetite particles was successfully visualized.

PMID- 19581717
TI  - In vivo internal diffusion of several inorganic microparticles through oral
      administration.
AB  - We observed the internal diffusion behavior of inorganic micro/nano particles
      through oral administration. By oral exposure, the fed particles were absorbed
      through the digestive system then reached some organs after internal diffusion in
      the body. For example, TiO2 particles fed to mice were detected in the lung,
      liver, and spleen after 10 days of feeding. Whereas, the absorption efficiency
      was extremely low compared with intravenous injection. In a comparison of the
      simple amount of administration, oral exposure required 102 times or more amount
      by intravenous injection for detection by an X-ray scanning analytical
      microscope. During dental treatment, micro/nano particles from tooth or dental
      materials would generate in the oral cavity, and some of the particles had a
      possibility to be swallowed, absorbed through the digestive system, and then
      diffuse into the body. However, our results suggest that biocompatible
      microparticles that are naturally taken orally affect animals only rarely because
      of the low absorption efficiency.

PMID- 19581718
TI  - Microstructures and biological influence of environmental exposure of asbestos.
AB  - Asbestos minerals are thin fiber type of minerals and honorably said as "the
      minerals of the miracle" because of their valuable natures even in the strategic
      field. On the other hand, the relation between asbestos exposure and diseases
      such as lung cancer and malignant mesothelioma was proved around 1970 by
      epidemiology and an animal experiment in relation to their microstructures. Here,
      microstructures of chrysotile asbestos, a mainstream of asbestos substances, are
      shown. It is also shown that in what kinds of environment people are exposed to
      asbestos and what kinds of biological or epidemical things happen after asbestos
      exposure. Many kinds of fibrous materials as the substitutes of asbestos are
      described in relation to their carcinogenicity.

PMID- 19581719
TI  - Calcium phosphate nanoparticles for the transfection of cells.
AB  - Transfection is a widely used method in molecular biology for the introduction of
      foreign nucleic acids (DNA or RNA) into eukaryotic cells that permits to control
      intracellular processes, i.e. the induction or inhibition of protein expression.
      Nucleic acids alone cannot penetrate the cell membrane, therefore special
      carriers like cationic polymers or inorganic nanoparticles are required. Single
      shell and multi-shell calcium phosphate nanoparticles were prepared and
      functionalized with DNA and siRNA. Thereby, the expression of enhanced green
      fluorescing protein (EGFP) can be induced (by using pcDNA3-EGFP) or silenced (by
      using siRNA). The single-shell nanoparticles were prepared by rapid mixing of
      aqueous solutions of calcium nitrate and diammonium hydrogen phosphate. The multi
      shell nanoparticles were produced by adding further layers of calcium phosphate
      and DNA to protect DNA from the intracellular degradation by endonucleases. The
      size of the nanoparticles according to dynamic light scattering and electron
      microscopy was up to 100 nm with a zeta potential around -30 mV. The transfection
      efficiency of the nanoparticles was tested in vitro in cell culture.

PMID- 19581720
TI  - Improved bond performance of a dental adhesive system using nano-technology.
AB  - Since adhesive technology was introduced into dental field, metal-based
      restoration has been gradually replaced by metal-free restoration. Using the
      adhesive technology, minimum invasive technique has been possible in daily
      clinical practice as well as esthetic tooth-colored restorations have become very
      popular all over the world.One of the current issues of the dental adhesive is
      durability of bond between tooth structure and adhesive resin. Several approaches
      to overcome the issues have been carried out. Self-etching approach is believed
      to create durable bond because demineralization of superficial tooth surface is
      very shallow. Other approach is to utilize the inhibitor of enzymes which are
      suggested to catalyze the decomposition of resin composites and are always
      secreted within the oral environment.In the present study, Colloidal Platinum
      Nanoparticles (CPN) was applied before the application of 4-META/MMA-TBB resin
      cement as the third possibility to prolong the durability of bond. This implies
      that the use of the CPN solution would create higher conversion at the interface
      compared with conventional bonding procedures.

PMID- 19581721
TI  - Research on the societal impacts of nanotechnology: a preliminary comparison of
      USA, Europe and Japan.
AB  - We initiate some comparisons between Japan, Europe and USA on how far there is
      governmental support for the ethical, legal, social and environmental dimensions
      of nanotechnology development. It is evident that in the USA and Europe
      nanotechnology is now firmly embedded in the consideration of ELSI. Yet Japan has
      not yet adequately recognized the importance of these dimensions. The history of
      bioethics in Japan is short. In Europe, as early as 2004, a nanotechnology report
      by the UK's Royal Society referred to the possibility of some nanotubes and
      fibres having asbestos-like toxicity. The negative history of asbestos in Europe
      and USA is not yet fully identified as a Japanese problem. Japan is therefore in
      the process of seeking how best to address societal aspects of nanotechnology.
      Should the precautionary principle be applied to Japan's nanotechnology
      initiative as in Europe? Should 5-10% of the government's nanotechnology budget
      be allocated to ELSI research and measures? We propose that the government and
      industrial sector in Japan play a much more proactive part in the regional and
      international growth of research into the wider risk assessment, social, health
      and environmental context of nanotechnologies, not simply try to borrow lessons
      from the West at a later date.

PMID- 19581722
TI  - Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in
      aged Alzheimer's disease mice.
AB  - We have recently shown that Alzheimer's disease (AD) transgenic mice given a
      moderate level of caffeine intake (the human equivalent of 5 cups of coffee per
      day) are protected from development of otherwise certain cognitive impairment and
      have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both
      beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To
      determine if caffeine intake can have beneficial effects in "aged" APPsw mice
      already demonstrating cognitive impairment, we administered caffeine in the
      drinking water of 18-19 month old APPsw mice that were impaired in working
      memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice
      given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the
      continuing impairment of control transgenic mice. In addition, Tg/Caff mice had
      substantially reduced Abeta deposition in hippocampus (decrease 40%) and
      entorhinal cortex (decrease 46%), as well as correlated decreases in brain
      soluble Abeta levels. Mechanistically, evidence is provided that caffeine
      suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined
      that caffeine concentrations within human physiological range effectively reduce
      active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with
      pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory
      restoration and reversal of AD pathology, suggesting a treatment potential of
      caffeine in cases of established AD.

PMID- 19581725
TI  - Microvascular benefits of increasing plasma viscosity and maintaining blood
      viscosity: counterintuitive experimental findings.
AB  - The circulation is adapted to specific levels of blood viscosity resulting in a
      balance that simultaneously sets peripheral vascular resistance, blood pressure
      and cardiac output, factors in part mediated by the production of nitric oxide by
      the endothelium. Although it is generally perceived that decreasing blood
      viscosity is beneficial for cardiovascular function, small increases of blood
      viscosity in normal healthy experimental subjects significantly improve
      cardiovascular function. These changes are within the normal variations of
      viscosity due to the variations of hematocrit in the healthy population.
      Hemodilution reduces blood viscosity, which is proposed to be physiologically
      beneficial. However, in extreme hemodilution, increased plasma viscosity via the
      use of viscogenic plasma expanders sustains microvascular and tissue function at
      significantly reduced levels of oxygen delivery. Studies in hemorrhagic shock
      resuscitation using oxygen carrying and non-carrying red blood cells show that
      restoration of blood viscosity is as important as restoration of oxygen carrying
      capacity. It is concluded that although hemodilution is indicated for reducing
      abnormally high blood viscosities, it is beneficial to increase plasma viscosity
      when hematocrit is reduced. Furthermore small increases in hematocrit may be
      beneficial due to the related increase in blood viscosity, independently of the
      increase of oxygen delivery capacity.

PMID- 19581723
TI  - Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's
      disease transgenic mice.
AB  - Recent epidemiologic studies suggest that caffeine may be protective against
      Alzheimer's disease (AD). Supportive of this premise, our previous studies have
      shown that moderate caffeine administration protects/restores cognitive function
      and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In
      the present study, we report that acute caffeine administration to both young
      adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain
      interstitial fluid and plasma without affecting Abeta elimination. Long-term oral
      caffeine treatment to aged AD mice provided not only sustained reductions in
      plasma Abeta, but also decreases in both soluble and deposited Abeta in
      hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels
      did not correlate with brain Abeta levels or with cognitive performance in
      individual aged AD mice. Although higher plasma caffeine levels were strongly
      associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine
      levels were also not linked to cognitive performance. Plasma caffeine and
      theophylline levels were tightly correlated, both being associated with reduced
      inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first,
      that both plasma and brain Abeta levels are reduced by acute or chronic caffeine
      administration in several AD transgenic lines and ages, indicating a therapeutic
      value of caffeine against AD; and second, that plasma Abeta levels are not an
      accurate index of brain Abeta levels/deposition or cognitive performance in aged
      AD mice.

PMID- 19581726
TI  - The cell-free layer in microvascular blood flow.
AB  - This review discusses the cell-free layer at the wall of the microcirculatory
      vessels with emphasis on the influence of blood rheological parameters on its
      formation as well as its possible effects on microvascular functions.
      Understanding cell-free layer characteristics in the microcirculation has been of
      increased interest for its possible influence on physiological function. The
      availability of better imaging and measurement techniques in recent years has
      created an excellent opportunity for researchers to examine the cell-free layer
      in much greater detail than possible previously. The most recent approach enables
      capturing spatial and temporal information of cell-free layer characteristics
      which can provide new insights to how cell-free layer width and its variations
      can impact physiological function. Cell-free layer formation is dependent on
      diameter of the vessel, flow rate, and rheological properties of blood including
      hematocrit, red blood cell aggregation, and deformability. Specifically in
      microvessels, its formation can also be affected by the presence of the
      glycocalyx layer that lines the luminal surface of the vessel wall. As the cell
      free layer is omnipresent in microcirculatory vessels, its formation at the
      vessel wall could affect function throughout the microvascular network by
      altering wall shear stress, local hematocrit, flow distribution, effective
      viscosity and nitric oxide production as well as its scavenging by red blood
      cells.

PMID- 19581727
TI  - Nonlinear elastic properties of polyacrylamide gels: implications for
      quantification of cellular forces.
AB  - Because of their tunable mechanical properties, polyacrylamide gels (PAG) are
      frequently used for studying cell adhesion and migratory responses to
      extracellular substrate stiffness. Since these responses are known to heavily
      depend on the tensional balance between cell contractility and substrate
      mechanical resistance, a precise knowledge of PAG's mechanical properties becomes
      quite crucial. Using the micropipette aspiration technique, we first exhibited
      the nonlinear elastic behavior of PAG and then successfully modeled it by an
      original strain-energy function. This function depends on the Poisson's ratio and
      on two material parameters, which have been explicitly related to acrylamide and
      bis-acrylamide concentrations. Implications of these results have been
      highlighted with regard to traction force microscopy experiments where cellular
      force quantification is derived from displacements of beads embedded in PAG. We
      found that considering PAG as a linear elastic medium tends to significantly
      underestimate traction forces for substrate displacements larger than 2 mum.
      Interestingly, we also showed that in the range of cellular force amplitude and
      PAG stiffness currently used in cell traction force experiments, finite size
      effects become critical for PAG substrate thickness below 60 mum. Thus, our
      improved characterization of PAG nonlinear mechanical properties through a new
      constitutive law could have significant impact onto biological experimentations
      where such extracellular substrates experience large strains.

PMID- 19581729
TI  - Dynamic compressive behavior of human meniscus correlates with its extra-cellular
      matrix composition.
AB  - The menisci of the knee play a significant role in the complex biomechanics of
      the joint and are critically important in maintaining articular cartilage health.
      While a general form-function relationship has been identified for the structural
      orientation of the extra-cellular matrix of the meniscus, the role of individual
      biochemical components has yet to be fully explored. To determine if correlations
      exist between the dynamic and static compressive modulus of human menisci and
      their major extra-cellular matrix constituents (collagen, glycosoaminoglycan and
      water content), 12 lateral and 11 medial menisci from 13 adult donors were
      examined. The results showed that in dynamic compression at high loading
      frequencies (0.1-1 Hz) the menisci behave as a rubber-like elastic material while
      at lower frequencies (0.01-0.03 Hz) significant viscous dissipation occurs. While
      regional variations in compressive moduli and extra-cellular matrix composition
      were observed, the magnitude of both dynamic and static compressive moduli were
      found to be insensitive to collagen content (p>0.4). However, this magnitude was
      found to significantly increase with increasing glycosaminoglycan content
      (p<0.001) and significantly decrease with increasing water content (p<0.001). The
      results of this study identify significant relationships between the viscoelastic
      behavior of the meniscus and its extra-cellular matrix composition.

PMID- 19581728
TI  - Identification, characterization and utilization of tumor cell selectin ligands
      in the design of colon cancer diagnostics.
AB  - The efficiency of secondary tumor establishment is controlled by the ability of
      tumor cells to withstand a barrage of mechanical and immunological stresses
      during their passage through the circulatory system. Accumulating evidence
      suggests that the selectin-dependent interactions of circulating tumor cells with
      host cells promote their survival and extravasation from the vasculature,
      therefore representing a critical checkpoint for colonization of distant organs.
      These observations have motivated the identification and biochemical
      characterization of functional selectin ligands such as CD44 variant isoforms,
      carcinoembryonic antigen and podocalyxin-like protein, present on the surface of
      metastatic colon carcinoma cells. Understanding the molecular underpinnings of
      selectin-ligand interactions involved in heterotypic tumor cell-host cell
      adhesion events may provide guidelines for developing novel cancer diagnostics.
      Recent advancements in diagnostic device fabrication and design integrated with
      novel biomarkers exploiting the tissue specific biochemistry of malignant versus
      normal tissue-expressed selectin ligands may hold promise in providing effective
      alternatives to current cancer diagnostic technologies.

PMID- 19581730
TI  - Simultaneous monitoring of electrical conductance and light transmittance during
      red blood cell aggregation.
AB  - The electrical properties of red blood cell (RBC) suspensions are influenced by
      flow conditions, and prior studies indicate that electrical properties may
      reflect the kinetics of RBC aggregation. Changes of conductance and capacitance
      were monitored and had a time course resembling a "syllectogram" (i.e., temporal
      change of light reflectance from an RBC suspension after sudden cessation of
      flow). In the present study, both AC electrical conductance (EC) across and light
      transmission (LT) through a 1 mm ID glass tube were recorded simultaneously after
      a sudden stoppage of flow for RBC at various hematocrits in plasma or in isotonic
      saline (PBS). Preliminary results indicate that EC and LT signals for RBC in
      plasma have similar time courses, both increasing after an initial decrement of a
      few seconds duration. Aggregation indexes and aggregation half times calculated
      using LT and EC showed a similar dependence on hematocrits between 30-50%.
      Interestingly, RBC in PBS also exhibited a syllectogram time course for
      conductance, whereas LT continued to decrease after an initial decline reflecting
      RBC shape recovery. These results suggest that electrical conductance in
      aggregating and non-aggregating suspensions may be sensitive to phenomena other
      than RBC aggregation.

PMID- 19581732
TI  - The use of real-time online updates for physicians.

PMID- 19581731
TI  - Comparison of three commercially available ektacytometers with different shearing
      geometries.
AB  - In December 2008, the International Society for Clinical Hemorheology organized a
      workshop to evaluate and compare three ektacytometer instruments for measuring
      deformability of red blood cells (RBC): LORCA (Laser-assisted Optical Rotational
      Cell Analyzer, RR Mechatronics, Hoorn, The Netherlands), Rheodyn SSD (Myrenne
      GmbH, Roetgen, Germany) and RheoScan-D (RheoMeditech, Seoul, Korea). Intra-assay
      reproducibility and biological variation were determined using normal RBC, and
      cells with reduced deformability (i.e., 0.001-0.02% glutaradehyde (GA), 48
      degrees C heat treatment) were employed as either the only RBC present or as a
      sub-population. Standardized difference values were used as measure of the power
      to detect differences between normal and treated cells. Salient results include:
      (1) All instruments had intra-assay variations below 5% for shear stress (SS)>1
      Pa but a sharp increase was found for Rheodyn SSD and RheoScan-D at lower SS; (2)
      Biological variation was similar and markedly increased for SS<3-5 Pa; (3) All
      instruments detected GA-treated RBC with maximal power at 1-3 Pa, the presence of
      10% or 40% GA-modified cells, and the effects of heat treatment. It is concluded
      that the LORCA, Rheodyn SSD and RheoScan-D all have acceptable precision and
      power for detecting reduced RBC deformability due to GA treatment or heat
      treatment, and that the SS range selected for the measurement of deformability is
      an important determinant of an instrument's power.

PMID- 19581733
TI  - Biomarkers for early detection and screening in pancreatic cancer. Highlights
      from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.
AB  - Pancreatic cancer is the second most frequent gastrointestinal malignancy with an
      unabated mortality that reflects the advanced stage of presentation. Detection of
      early disease through screening likely is the best way to meaningfully prolong
      survival. The development of biomarkers for screening holds enormous promise for
      increasing early detection and impacting mortality. Many biomarkers have been
      studied including the serum protein carbohydrate antigen 19-9, vascular
      endothelial growth factor, and nuclear factor kappa B, however, still no blood
      test or other fluid analysis reliably predicts patients with disease. The authors
      review abstracts from the 2009 annual meeting of the American Society of Clinical
      Oncology, Orlando, FL, U.S.A., that report evidence for early detection using a
      salivary biomarker array (#4630); a mucin epitope to PAM4 (#4613); a plasma
      nucleotide marker of hypoxia, miR-210 (#4624); and a cleavage product of
      complement pathway component C3b, iC3b (#4626). The meeting featured pancreatic
      cancer in over 100 research abstracts, of which, four are reviewed that focus on
      potential markers for early detection. When applied to a population of high risk
      patients, biomarkers of early pancreatic cancer could provide a minimally
      invasive way of identifying patients that require further evaluation using
      endoscopic tools. These molecular beacons may even be found to be sufficiently
      sensitive, specific, and cost effective to be applied to a broader population of
      patients.

PMID- 19581734
TI  - Pharmacogenetics in pancreatic cancer. Highlights from the 45th ASCO annual
      meeting. Orlando, FL, USA. May 29-June 2, 2009.
AB  - Cancer pharmacogenetics is a popular and evolving field in medicine with
      applications in various types of tumours helping clinicians to apply a more
      personalized medicine by providing information of prognostic, predictive and
      therapeutic value. Such evidence of pharmacogenetic applications is been already
      available in colon cancer (e.g. KRAS status, mismatch repair genes status, UGT1A1
      polymorphisms), lung cancer (EGFR mutations, ERCC1 mutations), breast cancer
      (HER2/neu overexpression) and many others. In all these tumors, the genetic
      information is rendering the management of the involved patients safer and more
      effective. Interesting abstracts and announcements from the perspective of
      pharmacogenomics in pancreatic cancer included Abstract #4611 which suggested the
      use of a novel genomic study able to detect specific single nucleotide
      polymorphisms (SNPs) with prognostic value, Abstract #4615 which showed that the
      known proteins alpha1-antitrypsin and alpha1-antichymotrypsin may be predictive
      of response to gemcitabine and survival, and Abstract #11097 which suggested that
      human R protein (HuR) expression may be a useful predictive biomarker of
      gemcitabine treatment. The authors also present here a few other abstracts of
      pharmacogenomic interest which had negative findings, but believed to be of
      clinical importance.

PMID- 19581735
TI  - Any progress in the management of advanced pancreatic cancer? Highlights from the
      45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.
AB  - Majority of the patients with pancreatic cancer present with advanced disease
      that is lethal and notoriously difficult to treat. Survival has not improved
      dramatically despite routine use of chemotherapy and radiotherapy; this situation
      signifies an urgent need for novel therapeutic approaches. The treatment of
      advanced disease with gemcitabine has only a modest activity on survival with a
      favorable impact on quality of life. So far, the current targeted agents that
      have been used in combination with gemcitabine have failed to improve clinical
      outcomes. This failure may stem from the heterogeneous molecular pathogenesis of
      pancreatic cancers, which involves several oncogenic pathways and defined genetic
      mutations. However, recent data support the evidence that the combination of
      gemcitabine with erlotinib, capecitabine or platinum compounds could be more
      active than gemcitabine alone in advanced pancreatic cancer. New therapeutic
      strategies, particularly using molecular target agents, are under evaluation. A
      number of molecular mechanisms responsible of transformation and progression of
      pancreatic cancer have been identified, opening the possibility to identify also
      possible pharmacological targets. Pancreatic cancer remains the 4th leading cause
      of cancer death in the U.S.A.. How to treat a non-resectable pancreatic cancer
      has been a challenging topic for all medical oncologists. Historical 5
      fluorouracil has been replaced by single agent gemcitabine since 1997. Numerous
      combinations using gemcitabine as a backbone have been tested in clinical trials;
      unfortunately, none of the combinations including the ones with biological agents
      was proved to be significantly superior to gemcitabine alone. This year, more
      combinations were investigated and the results were presented on the meeting. In
      first-line setting, two large phase III trials (Abstracts #4504 and #4601) failed
      to prove any additional benefit of a second cytotoxic agent or a vaccine. Folinic
      acid plus 5-FU plus oxaliplatin (FOLFOX) and 5-fluorouracil plus leucovorin plus
      irinotecan (FOLFIRI) could be considered in the second-line setting after failure
      of gemcitabine therapy (Abstract #4618). Novel agents (Abstracts #4501, #4625,
      #4626, #4617) provide some hope; however, in general, all combinations are still
      significantly relying on the backbone of gemcitabine. Thinking beyond the
      gemcitabine box and exploring novel agents are very crucial now.

PMID- 19581736
TI  - New developments in the treatment of locally advanced pancreatic cancer.
      Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2,
      2009.
AB  - The results of the trials presented at this year's ASCO annual meeting underline
      the challenges of not only treating but also studying locally advanced pancreatic
      cancer, with any appreciable effect of treatment gained at the cost of
      considerable toxicity. That response was observed in small numbers of patients in
      the presented trials speaks to the importance of rational selection of treatment
      in individual patients in order to achieve maximal survival with minimal
      treatment-associated morbidity. Further understanding of tumor biology and
      identification of both prognostic and predictive factors will help define
      personalized treatment approaches for individual patients.

PMID- 19581737
TI  - Adjuvant treatment of pancreatic cancer in 2009: where are we? Highlights from
      the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.
AB  - Despite attempted curative resection of localized pancreatic adenocarcinoma, most
      patients succumb a recurrence and die of their disease. The Gastrointestinal
      Tumor Study Group, European Organization for Research and Treatment of Cancer,
      and European Study Group for Pancreatic Cancer trials have suggested the benefit
      of adjuvant therapy. However, the relatively few randomized trials available have
      not established a definite standard of care due to study limitations. Although
      these trials, and the recently published Charite Onkologie (CONKO)-001 trial,
      have shown a definite advantage of adjuvant chemotherapy, the most effective
      chemotherapy and the role of radiation therapy remain unclear. This review will
      discuss the data available from reported trials of adjuvant therapy in pancreatic
      cancer, especially the results of the ESPAC-3 study presented at the annual
      meeting of ASCO 2009, and consider future directions for clinical trials.

PMID- 19581738
TI  - Syndecan-1 and tenascin expression in cystic tumors of the pancreas.
AB  - CONTEXT: Since benign and malignant mucin-producing tumors of the pancreas may be
      difficult to distinguish from each other; preoperative methods for differential
      diagnosis would reduce unnecessary surgery. OBJECTIVE: To compare syndecan-1 and
      tenascin immunoexpression in benign and malignant cystic pancreatic tumors.
      DESIGN: We used immunohistochemical staining for syndecan-1 and tenascin
      antibodies in tumor tissue samples. SETTING: Helsinki University Central
      Hospital. PATIENTS: Tissue material came from 33 patients undergoing surgery from
      1979 to 2005 for cystic pancreatic tumors. RESULTS: A statistically significant
      difference appeared in syndecan-1 expression between benign (mucinous cystic
      neoplasms and intraductal papillary mucinous neoplasms) and mucinous carcinomas,
      but there was no significant difference in tenascin immunoexpression between
      these tumor groups. CONCLUSION: Our findings suggest that low syndecan-1
      expression might serve as a predictive factor for malignancy in cystic tumors of
      the pancreas.

PMID- 19581739
TI  - Prevalence of type III anomalous pancreaticobiliary junction in a tertiary care
      hospital of North India.
AB  - CONTEXT: Anomalous junction of pancreaticobiliary ducts is a condition in which
      the pancreatic duct and the bile duct join outside the duodenal wall with a long
      common channel. The most accepted classification of various types of anomalous
      pancreaticobiliary junction is the new Komi classification. The majority of cases
      of type III anomalous pancreaticobiliary junction are reported from Japan and
      very seldom from outside Japan. This study evaluates the prevalence of type III
      anomalous pancreaticobiliary junction in the Indian population. OBJECTIVE: To
      retrospectively evaluate the prevalence of type III anomalous pancreaticobiliary
      junction revealed by endoscopic retrograde cholangiopancreatography (ERCP)
      examinations carried out between 1985 and 2005. DESIGN: ERCP records of 3,827
      patients satisfying inclusion criteria between 1985 and 2005 were retrospectively
      analyzed. MAIN OUTCOME MEASURE: Patients demonstrating anomalous
      pancreaticobiliary junction were identified and classified according to the new
      Komi classification. RESULTS: A total of 101 patients had anomalous
      pancreaticobiliary junction (2.6% of all ERCP). Only 2 patients (2.0% of all
      anomalous pancreaticobiliary junction cases and 0.05% of all ERCP examinations)
      had type III anomalous pancreaticobiliary junction. Both cases were associated
      with choledochal cysts and chronic pancreatitis. CONCLUSION: Type III anomalous
      pancreaticobiliary junction is a rare occurrence in Indian patients as compared
      to Japanese patients in whom the majority of cases are reported. This demographic
      variation is still unexplained.

PMID- 19581740
TI  - Alcohol as a risk factor for pancreatitis. A systematic review and meta-analysis.
AB  - CONTEXT: Epidemiologic studies have suggested an association between alcohol
      consumption and pancreatitis, although the exact dose-response relationship is
      unknown. It also remains uncertain whether a threshold effect exists. OBJECTIVE:
      To conduct a systematic review and meta-analysis of epidemiologic studies on the
      association between alcohol consumption and the risk of pancreatitis. METHODS: We
      searched Ovid MEDLINE, EMBASE, CINAHL, Web of Science, ETOH and AIM. Studies were
      included if they reported quantifiable information on risk and related confidence
      intervals with respect to at least three different levels of alcohol intake.
      RESULTS: Six studies, including 146,517 individuals with 1,671 cases of
      pancreatitis, met the inclusion criteria. We found a monotonic and approximately
      exponential dose-response relationship between average volume of alcohol
      consumption and pancreatitis. However, in a categorical analysis the lower
      drinking categories were not significantly elevated, with an apparent threshold
      of 4 drinks daily. CONCLUSIONS: As the available evidence also indicates that the
      relationship is biologically plausible, these results support the existence of a
      link between alcohol consumption and the risk of pancreatitis.

PMID- 19581741
TI  - Sirolimus can reverse resistance to gemcitabine, capecitabine and docetaxel
      combination therapy in pancreatic cancer.
AB  - CONTEXT: Treating patients with metastatic carcinoma of the pancreas can lead to
      regression of disease, but the tumor becomes resistant to therapy within a few
      months. If resistance can be reversed or prevented, the chemotherapeutic benefit
      may be prolonged. CASE REPORTS: Two patients with metastatic pancreatic cancer
      progressed on gemcitabine, capecitabine and docetaxel (GTX). When sirolimus was
      added to this regimen at a dosage to achieve a serum level of at least 10 ng/dL
      at the time of the gemcitabine and docetaxel infusion, their tumors regressed.
      CONCLUSION: This demonstrates that the addition of sirolimus to a
      gemcitabine/docetaxel containing regimen can reverse tumor resistance in the
      clinical setting.

PMID- 19581742
TI  - Pancreatic metastasis from nephroblastoma: an unusual entity.
AB  - CONTEXT: Pancreatic metastasis from renal cell carcinoma is a well-known entity.
      When metastatic disease is limited to the pancreas, pancreatic resection is the
      optimal treatment. A nephroblastoma is a frequent childhood cancer but can also
      occur in adults. A metastatic nephroblastoma mainly affects the lung and the
      liver. Pancreatic metastases from a nephroblastoma are very rare. CASE REPORT: We
      report an extremely rare case of pancreatic metastases in a 20-year-old man who
      had a right nephroblastoma resected at 9 years of age and liver metastases
      treated by right hepatectomy at 18 years of age. Pancreatic metastasis was
      revealed by acute pancreatitis. Imaging studies revealed one 2 cm nodule in the
      pancreatic head with upstream dilatation of the Wirsung duct. Imaging studies
      revealed no other localization except a 1.5 cm liver nodule. Surgical resection
      was performed without preoperative chemotherapy because the patient was
      symptomatic and had already received numerous chemotherapy protocols. The patient
      underwent pancreaticoduodenectomy and limited liver resection with an uneventful
      postoperative course. Pathological examination confirmed pancreatic and liver
      metastases from a nephroblastoma composed of blastematous cells mixed with
      embryonic tubular structures without lymph node metastases. After resection, the
      patient received adjuvant high dose chemotherapy with autologous hematopoietic
      stem-cell support. After a 21-month follow-up, the patient was in good general
      condition but had liver recurrence without intra-pancreatic recurrence.
      CONCLUSION: This is probably the first case of pancreatic metastasis from a
      nephroblastoma reported in a living patient. A nephroblastoma, like clear cell
      renal carcinoma, can be considered a possible etiology of pancreatic metastasis
      from a primary renal tumor.

PMID- 19581743
TI  - Intrapancreatic accessory spleen issues: diagnostic and therapeutic challenges.
AB  - CONTEXT: Intrapancreatic accessory spleen is an exceptionally rare entity,
      commonly mistaken for a pancreatic neoplasm. Preoperative diagnosis based on
      radiologic imaging features is difficult. Aspiration cytology may be misleading
      due to poor sampling. CASE REPORT: We report a very rare case of an
      intrapancreatic accessory spleen which radiologically and cytologically mimicked
      a neuroendocrine pancreatic tumor. CONCLUSION: Modern imaging techniques will
      probably lead to an increasing number of intrapancreatic accessory spleens being
      discovered, posing significant diagnostic and therapeutic challenges.

PMID- 19581744
TI  - Small undifferentiated pancreatic adenocarcinoma which mimics IPMN at imaging.
AB  - CONTEXT: To present the case of an unusual presentation at imaging of a very
      small solid undifferentiated pancreatic adenocarcinoma which mimics a side-branch
      intraductal papillary mucinous neoplasm. CASE REPORT: The patient came to our
      hospital for a revaluation of a cystic pancreatic lesion. Ultrasound (US) and
      contrast-enhanced ultrasound (CEUS) examinations were carried out. A small cystic
      lesion of about 1.5 cm in diameter was seen in the posterior aspect of the
      pancreatic uncinate process A very small, solid, vascularized nodule was detected
      at CEUS within the lesion. Consequently, the patient underwent CT and MRI. MRI
      confirmed the presence of an intralesional nodule and communication with the main
      pancreatic duct was demonstrated, suggesting the diagnosis of intraductal
      papillary mucinous neoplasm with solid intralesional tissue. A pylorus preserving
      pancreaticoduodenectomy was carried out. An undifferentiated adenocarcinoma
      having a notable peripheral inflammatory reaction and dilated branch duct was
      finally diagnosed. CONCLUSION: To our knowledge, we present for the first time,
      the case of a very small solid undifferentiated pancreatic adenocarcinoma of the
      uncinate process which mimicked a side-branch intraductal papillary mucinous
      neoplasm at imaging. The cystic appearance may be an epiphenomenon of a solid
      lesion and this possibility has to be considered when one encounters incidental
      cystic lesions at imaging.

PMID- 19581745
TI  - EUS-guided Trucut biopsies may enable the diagnosis of lymphoepithelial cysts of
      the pancreas. Report of two cases.
AB  - CONTEXT: Lymphoepithelial cysts are rare benign lesions of the pancreas.
      Endoscopic ultrasound guided fine needle aspiration (FNA) has reportedly been
      helpful in reaching a diagnosis of lymphoepithelial cyst. In cases where it may
      be difficult to obtain a diagnosis using FNA a histological sample may be
      obtained using EUS guided Trucut biopsy. CASE REPORTS: We describe two cases of
      lymphoepithelial cysts where a diagnosis of lymphoepithelial cyst was made using
      EUS guided Trucut biopsy. CONCLUSION: In some case, lymphoepithelial cysts may
      present a diagnostic dilemma. EUS with FNA and Trucut biopsy may enable the
      clinician to make a definitive diagnosis.

PMID- 19581746
TI  - Pancreatic metastasis from renal carcinoma managed by Whipple resection. A case
      report and literature review of metastatic pattern, surgical management and
      outcome.
AB  - CONTEXT: Metastatic cancer to the pancreas is rare and accounts for less than 2%
      of all pancreatic malignancies, metastasis from renal cell carcinoma being
      predominant. While symptomatic patients present with obstructive jaundice,
      abdominal pain, or GI bleeding, the diagnosis is often made in asymptomatic
      patients during follow-up for renal cell carcinoma. Hence, a high index of
      clinical suspicion is required in a patient who presents with a pancreatic tumor
      following a nephrectomy for renal cell carcinoma. CASE REPORT: We report the case
      of a patient in whom a lesion was detected in the head of the pancreas, following
      a nephrectomy performed 5 years previously for renal cell carcinoma. A magnetic
      resonance scan revealed a well-defined lesion in the head of the pancreas. The
      patient underwent a pancreaticoduodenectomy and histopathology confirmed a
      metastatic renal cell carcinoma. Two years after the surgery, the patient is
      doing well. The literature is reviewed for pancreatic metastasis from renal cell
      carcinoma, for metastatic pattern, surgical management and outcome. CONCLUSION:
      Pancreatic metastases are usually detected during the follow-up of patients
      having undergone a previous nephrectomy for renal cell carcinoma. Typically, the
      interval between a nephrectomy and pancreatic metastasis is long. The literature
      contained more than 250 cases of pancreatic resection for metastatic renal cell
      carcinoma. The median duration of presentation was 10.5+/-6.5 years following a
      nephrectomy. The lesions are multifocal (3.2+/-1.5) in about 39% of patients and
      resectable in 80%. A high resectability rate is characteristic of metastasis from
      renal cell carcinoma as compared to primary pancreatic cancer. The five year
      survival rate is between 43 and 88%.

PMID- 19581747
TI  - Heterotopic pancreas in the jejunum presenting as a submucosal lesion on
      endoscopy.
AB  - CONTEXT: Ectopic pancreas can occur anywhere in the gastrointestinal tract with
      the stomach and small bowel being the most common sites. The endoscopic
      appearance of the ectopic pancreas in the small bowel has rarely been reported.
      CASE REPORT: We report the case of a 45-year-old female with heterotopic pancreas
      in the jejunum who presented with recurrent episodes of abdominal pain and had a
      submucosal lesion on endoscopy. As she had undergone gastrojejunostomy in the
      past, the lesion in the jejunum could be diagnosed on endoscopy by entering the
      efferent loop. CONCLUSION: Heterotopic pancreas should be considered when making
      a differential diagnosis of submucosal lesions in the small bowel.

PMID- 19581748
TI  - A wayward cyst.
AB  - CONTEXT: Pseudocysts are a common complication of acute and chronic pancreatitis.
      These are usually located within the pancreas but they can occur at other sites
      as well, including the mediastinum, neck, pelvis and rarely in the liver as in
      our case. The diagnosis of intrahepatic pancreatic pseudocyst relies on the
      demonstration of a high amylase level in the sampled cystic fluid in the absence
      of infection or neoplasm. CASE REPORT: A 60-year-old man with a history of
      chronic pancreatitis presents with a clinical and laboratory picture suggestive
      of acute exacerbation of his pancreatitis. A computed tomogram (CT) scan of the
      abdomen revealed a pancreatic pseudocyst and a cystic lesion involving both lobes
      of the liver. CT diagnostic aspiration of the intrahepatic cyst revealed high
      amylase level (greater than 20,000 U/L). The cyst was treated with percutaneous
      drainage with complete resolution of the cyst. CONCLUSION: In the setting of
      pancreatitis, intrahepatic pancreatic pseudocyst should be considered in the
      differential diagnosis of cystic lesion of the liver.

PMID- 19581749
TI  - Pancreas preserving total duodenectomy for complex duodenal injury.
AB  - CONTEXT: To assess the feasibility and safety of a pancreas-preserving total
      duodenectomy in the management of severe duodenal injury caused by abdominal
      trauma. CASE REPORT: Two patients with both extensive injury of the duodenum and
      diffuse peritonitis underwent pancreas preserving total duodenectomy at our
      tertiary care centre. These two young male patients (age 20 and 22 years)
      presented 2 days and 6 hours respectively following blunt abdominal trauma. The
      duodenum was almost completely separated from the pancreas. Ampulla was seen as a
      button on the pancreas. Following total duodenectomy, reconstruction was
      performed by suturing the jejunum to the head of the pancreas anteriorly and
      posteriorly away from the ampulla (invagination of the pancreas into the
      jejunum). There were no complications attributable to the procedure. Both
      patients are well on follow up. CONCLUSION: A Pancreas-preserving total
      duodenectomy offers a safe alternative to the Whipple procedure in managing
      complex duodenal injury. This procedure avoids unnecessary resection of the
      adjacent pancreas and anastomosis to undilated hepatic and pancreatic ducts.

PMID- 19581750
TI  - Solitary true cyst of the pancreas in adults. A report of two cases.
AB  - CONTEXT: Solitary true cysts of the pancreas in adults are extremely rare and
      only few cases have been reported in the literature. The etiology and natural
      history of these lesions remain unknown and treatment is not standardized. We
      describe two additional resected cases. CASE REPORTS: The first patient was a
      young woman with an incidental 3 cm cyst located in the pancreatic head who
      underwent enucleation. The second patient was a young woman with a large 8 cm
      symptomatic cyst located in the pancreatic tail who underwent a laparoscopic
      spleen-preserving distal pancreatectomy. Histological examination revealed
      fibrous walls lined by a monolayer of cuboidal epithelium in both cases.
      CONCLUSIONS: A preoperative work-up alone does not always allow an accurate
      diagnosis, but it is useful in determining lesion characteristics and guiding
      therapeutic decision making. When surgery is indicated, a limited resection is
      warranted in most cases.

PMID- 19581751
TI  - IgG4-related retroperitoneal fibrosis and sclerosing cholangitis independent of
      autoimmune pancreatitis. A recurrent case after a 5-year history of spontaneous
      remission.
AB  - CONTEXT: A new clinicopathological concept of IgG4-related sclerosing disease
      affecting various organs has recently been proposed in relation to autoimmune
      pancreatitis. This report describes the case of IgG4-related retroperitoneal
      fibrosis and sclerosing cholangitis independent of autoimmune pancreatitis, which
      recurred after a long period of spontaneous remission. CASE REPORT: An 80-year
      old Japanese man presented with obstructive jaundice owing to a hepatic hilum
      bile duct stricture. Coincidentally, a soft tissue mass surrounding the abdominal
      aorta, suggesting retroperitoneal fibrosis, was identified. Unexpectedly,
      spontaneous regression of obstructive jaundice together with retroperitoneal
      fibrosis occurred. The presence of high serum IgG4 concentrations measured later
      led us to consider a possible association with autoimmune pancreatitis; however,
      there were no clinical features confirming autoimmune pancreatitis. After a 5
      year history of spontaneous clinical remission, there was an elevation of serum
      IgG4 levels and renal dysfunction owing to bilateral hydronephrosis caused by a
      reemergence of the retroperitoneal mass. Evaluation by endoscopic retrograde
      cholangiopancreatography revealed a biliary stricture, suggesting sclerosing
      cholangitis which was observed without the presence of any pancreatic duct
      abnormality. The subsequent excellent results obtained using steroid therapy,
      namely the decrease in serum IgG4 levels and the regression of the
      retroperitoneal mass, strongly suggested that the present case was an IgG4
      related sclerosing disease. Aside from high serum IgG4 concentrations, markedly
      elevated levels of serum IgE was found retrospectively, although the clinical
      significance remains unknown. CONCLUSION: When we encounter fibrotic diseases of
      unknown etiology, we should measure serum IgG4 concentrations and monitor the
      disease activity over long periods even after achieving clinical remission.

PMID- 19581752
TI  - A case of primary vertebral osteosarcoma metastasizing to pancreas.
AB  - CONTEXT: Osteosarcoma is the most common malignant bone tumor in children and
      adolescents and possesses a high potential for metastasis. The most common sites
      of osteosarcomatous metastases are the lungs, pleurae, and bone; the pancreas
      being extremely rare. CASE REPORT: We report the computed tomography findings of
      a rare case of pancreatic metastasis in a 14-year-old boy with primary vertebral
      osteosarcoma being followed-up for 6 years. On abdominal CT, a huge mass
      containing necrotic and calcified areas and causing bone destruction was seen
      between thoracic vertebra 7 and sacral vertebra 1 involving both the vertebrae
      and paravertebral soft-tissue. A large metastatic mass with an irregular contour
      was also visualized in the pancreatic head and peripancreatic region having
      tomographic findings similar to the vertebral mass. Tru-cut biopsy of the
      pancreatic mass confirmed the diagnosis of osteosarcoma metastasis. CONCLUSIONS:
      Although extremely rare, osteosarcoma metastasis should be included in the
      differential diagnosis of pancreatic mass lesions, particularly in patients with
      a primary tumor.

PMID- 19581753
TI  - Pseudoaneurysmal rupture of the common hepatic artery into the biliodigestive
      anastomosis. A rare cause of gastrointestinal bleeding.
AB  - CONTEXT: Pseudoaneurysm of the hepatic artery after a pancreaticoduodenectomy is
      a serious complication, which should always be considered in the differential
      diagnosis when late bleeding has occurred. CASE REPORT: We report a case of
      pseudoaneurysmal rupture of the common hepatic artery into the biliodigestive
      anastomosis. A 55 year old female patient with a history of pancreatic head
      cancer underwent a pylorus preserving pancreaticoduodenectomy at our hospital in
      September 2008. Six days postoperatively the patient underwent surgery because of
      sentinel bleeding of a portal vein branch. On the 40th postoperative day she
      presented melena. Upper gastrointestinal endoscopy indicated bleeding near the
      biliodigestive anastomosis. An emergency angiography demonstrated a
      pseudoaneurysm of the common hepatic artery. Transcatheter arterial embolization
      was performed and a hemodynamic stabilization of the patient was achieved. Six
      days after the embolization the patient developed hemorrhagic shock and an urgent
      relaparotomy was carried out. The explorative laparotomy revealed bleeding of the
      common hepatic artery into the biliodigestive anastomosis in the form of an
      arteriointestinal fistula. The anastomosis was opened, the ruptured
      pseudoaneurysm was sutured, and a new biliodigestive anastomosis was made. The
      patient has been well for two months with good liver function, without
      rebleeding. CONCLUSION: This case illustrates the occurrence of a rare
      complication (rupture of a hepatic artery pseudoaneurysm) inside the
      biliodigestive anastomosis after pancreaticoduodenectomy, appearing as upper
      gastrointestinal bleeding. Different modalities such as transarterial
      embolization and the use of stents give promising results, but ligation of the
      pseudoaneurysm and repair of the intestinal communication is also an effective
      modality of treatment.

PMID- 19581754
TI  - Late failure of Frey procedure due to gastro-jejunal fistula formation.
AB  - CONTEXT: Local resection of the pancreatic head with longitudinal
      pancreaticojejunostomy (or Frey procedure) generally results in excellent pain
      relief in chronic pancreatitis. We report a patient with chronic pancreatitis who
      experienced pain recurrence after an uneventful longitudinal
      pancreaticojejunostomy. CASE REPORT: This is a single case study of a 58-year-old
      female with chronic pancreatitis undergoing longitudinal pancreaticojejunostomy
      for pain relief. Fifteen months after the surgery, the patient experienced pain
      recurrence. Radiologic evaluation followed by surgical exploration revealed a
      gastroenteric fistula to the Roux-limb, with obliteration of the anastomosis.
      After repair of the fistula and re-excavation of the pancreatic head, a two-layer
      longitudinal pancreaticojejunostomy was reconstructed from the same Roux-limb. An
      omental flap was interposed between the Roux limb and the repaired stomach. At 6
      month follow-up, the patient was pain free and asymptomatic. CONCLUSION: Late
      failure of the Frey procedure due to a gastroenteric fistula to the Roux-limb of
      jejunum has not been previously reported. This finding may explain one of the
      causes of longitudinal pancreaticojejunostomy late failure.

PMID- 19581755
TI  - Managing unsuspected tumour invasion of the superior mesenteric-portal vein
      during surgery for pancreatic head cancer. A case report.
AB  - CONTEXT: In some cases, synchronous superior mesenteric-portal vein resection can
      be performed during pancreatic resection for cancer. The reconstruction technique
      is usually primary anastomosis; in only a few cases is an autologous vein graft
      needed. CASE REPORT: We report a case of reconstruction of the superior
      mesenteric-portal vein with a splenic vein autograft in a patient affected by
      pancreatic head adenocarcinoma who underwent a total pancreatectomy. CONCLUSIONS:
      The reconstruction of the superior mesenteric-portal vein with a splenic vein
      autograft should be performed in selected cases. It allows a reduction of
      operating time, it is a less invasive approach than reconstruction using an
      internal jugular vein autograft and it can be an oncologically correct approach.

PMID- 19581756
TI  - Primary pancreatic tuberculosis masquerading as a pancreatic tumor leading to
      Whipple's pancreaticoduodenectomy. A case report and review of the literature.
AB  - A 45-year-old female presented with upper abdominal pain. Ultrasound and CECT
      both showed a mass in the pancreatic head and uncinate process suggestive of
      carcinoma of the head of the pancreas. A Whipple's pancreaticoduodenectomy was
      carried out. Microscopic examination showed numerous epithelioid cell granulomas
      in the pancreas infiltrating the duodenal mucosa. No evidence of malignancy was
      seen. Acid fast bacilli were positive. The patient was started on anti-tubercular
      therapy. Cases of isolated pancreatic tuberculosis are very rare and can mimic
      pancreatic carcinoma clinically and radiologically. A differential diagnosis of
      pancreatic tuberculosis must be made in a patient presenting with a pancreatic
      mass and the patient must be thoroughly investigated to confirm or rule out
      malignancy or tuberculosis. We herein present a case of primary pancreatic
      tuberculosis and discuss the clinicopathological features of this condition. We
      have also proposed an algorithm for the management of patients presenting with a
      pancreatic mass and a clinical suspicion of pancreatic tuberculosis.

PMID- 19581757
TI  - Mutations in the SLC29A3 gene are not a common cause of isolated autoantibody
      negative type 1 diabetes.

PMID- 19581759
TI  - Increase in annual number of pancreatic head resections does not affect mortality
      of pancreatic cancer in the United Kingdom.

PMID- 19581758
TI  - Oxaliplatin-induced hyperexcitability syndrome in a patient with pancreatic
      cancer.
AB  - A recent pooled analysis and a meta-analysis suggested a survival benefit of
      gemcitabine-platinum doublets when compared with single agent gemcitabine in
      pancreatic cancer. Sensory neurotoxicity is a potentially limiting toxicity
      associated with oxaliplatin therapy. In this letter, we describe a case of a
      patient with metastatic pancreatic cancer who developed acquired neuromyotonia
      while receiving intravenous oxaliplatin as part of her treatment. It is a
      condition characterized by cramps, muscle twitching, weakness, myotonia and
      pseudomyotonia (slow muscle relaxation after forceful contraction). Her symptoms
      were ameliorated after initiation of pregabalin. We postulate that
      hyperexcitability syndrome associated with administration of oxaliplatin can be
      treated with pregabalin. Future studies will be needed to confirm this as well as
      to determine the long-term adverse effects associated with pregabalin.

PMID- 19581761
TI  - Diabetes genetics. A seventh sense for the successful sequel of 'come together'.
      "The genotypes and phenotypes of diabetes". Bergen, Norway. April 22-26, 2009.
      2nd meeting of 'EASD Study Group on Genetics of Diabetes' and 44th annual meeting
      of the 'Scandinavian Society for the Study of Diabetes'.

PMID- 19581762
TI  - Pancreatic stellate cells and pancreatic carcinoma: an unholy alliance.

PMID- 19581763
TI  - [Clevudine therapy in patients with chronic hepatitis B].

PMID- 19581764
TI  - [Pathology of nonalcoholic steatohepatitis].
AB  - Nonalcoholic steatohepatitis (NASH), one of the NAFLDs (nonalcoholic fatty liver
      diseases), is regarded as a hepatic manifestation of metabolic syndrome. NASH can
      progress to cirrhosis, and possibly to hepatic malignancy. Currently, liver
      biopsy is the only reliable method of assessing the presence or absence of NASH
      and the stage of fibrosis. The finding of steatosis with evidence of hepatocyte
      injury such as inflammation, ballooning, degeneration, and/or fibrosis, is
      generally essential for making a diagnosis of NASH. However, its diagnostic
      criteria have not yet been established. The pathologic findings of NASH and
      related diseases, and the grading system currently in use are reviewed herein.

PMID- 19581765
TI  - [Change in the serologic markers of hepatitis B after allogenic hematopoietic
      stem-cell transplantation].
AB  - BACKGROUND/AIMS: This study examined the effects of hepatitis B virus (HBV)
      infection state and immunologic capability in both the recipients and donors of
      allogenic hematopoietic stem-cell transplantation (allo-HSCT) on changes in HBV
      serologic markers in recipients. METHODS: A total of 537 patients underwent allo
      HSCT for the treatment of leukemia, malignant lymphoma, and solid tumor. HBV
      serologic markers were examined in both recipients and donors prior to and
      following the transplantation. The mean follow-up period was 36.6 months (range 3
      80 months). RESULTS: Of the 537 patients who underwent allo-HSCT, 45 recipients
      were positive for HBsAg prior to transplantation. Of these 45 patients, 21 were
      transplanted from anti-HBs-positive donors and the remaining 24 were transplanted
      from anti-HBs-negative donors. In the former cases, seroconversion was noted in 4
      of the 21 patients (19%). In the latter cases, however, no seroconversion was
      noted following the transplantation. Thirty patients who were negative for both
      HBsAg and anti-HBs were transplanted from anti-HBs-positive donors, and 15 out of
      30 patients (50%) acquired anti-HBs. Four hundred and seven patients who were
      positive for anti-HBs were transplanted from anti-HBs-positive or HbsAg-negative
      donors; 8 of these proved HBsAg-positive following the transplantation. There
      were no changes in HBV serological markers following transplantation in 41
      patients who were transplanted from HbsAg-positive donors. CONCLUSIONS: Due to
      the adoptive immunity that was transferred from anti-HBs-positive donors, a
      seroconversion of HBsAg could occur in some HBsAg-positive recipients. HBsAg
      positive donors had a lesser effect on the HBV serologic markers of recipients.
      However, a reactivation of HBV can occur following hematopoietic stem-cell
      transplantation in the cases of recipients or donors with a history of HBV,
      infection by an accompanying immune suppression. Therefore, prevention should be
      instigated.

PMID- 19581766
TI  - [Distribution of hepatitis B virus genotypes in Korea].
AB  - BACKGROUND/AIMS: Considering the incidence of prevailing hepatitis B virus (HBV)
      genotypes in neighboring nations, the predominance of genotype C in Korea is
      exceptional and needs to be confirmed by nationwide investigation. METHODS: A
      total of 510 HBsAg (+) or HBeAg (+) serum samples was collected from subjects in
      several cities and harbors throughout the Korean peninsula for genotype (A-G)
      specific multiplex PCR analysis. Another 40 serum samples from chronic HBV
      carriers from Iksan city were selected for sequencing of the entire HBV genome.
      Phylogenetic analysis was performed with 22 whole genomic sequences of Korean HBV
      strains enrolled in GenBank. RESULTS: An amplicon was found in 377 specimens and
      genotype C occupied 98.1% (370 cases); none of the other genotypes were found. A
      mixed pattern of genotypes B and C was seen in seven specimens (1.9%), of which
      five were tested using PCR targeting the X fragment; no genotype B bands were
      found. With the exception of 1 case, which was subgenotype A2, whole sequences of
      Korean HBV strains (n=62) belonged to subgenotype C2. CONCLUSIONS: The prevailing
      HBV genotype in Korea is C2; the other genotypes occur only rarely. Future
      studies should include confirmation of the detection of genotypes other than C.

PMID- 19581767
TI  - [Analysis of the clinical characteristics and prognostic factors of ruptured
      hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Spontaneous rupture of hepatocellular carcinoma (HCC) is a rare
      but life-threatening complication. Although the prevalence rate and mortality of
      HCC has been reportedly high in Korea, studies on ruptured HCC are limited. The
      aim of this study was to determine the clinical characteristics and prognostic
      factors of ruptured HCC. METHODS: Among 886 cases with HCC that had been
      diagnosed at Chonnam National University Hospital from January 2002 to December
      2007, 62 cases (7.0%) with ruptured HCC were studied retrospectively regarding
      their clinical characteristics and prognostic factors. RESULTS: Transarterial
      embolization was performed in 56 cases (90.3%) to control bleeding, with a
      hemostasis success rate of 89.3%. The survival time after the rupture of HCC was
      8.0+/-1.7 months (mean+/-SD), although it was longer in HCC cases that were first
      diagnosed in a ruptured state or ruptured with a small amount of bleeding than in
      those that ruptured during follow-up after diagnosis or with a large amount of
      bleeding, respectively. The 30-day mortality rate in patients with a ruptured HCC
      was 43.5%, and the early deaths were independently associated with the presence
      of hepatic encephalopathy (odds ratio, OR=44.7; 95% confidence interval, CI=1.9
      1051.1; P=0.018), serum bilirubin >3.0 mg/dL (OR=36.7; 95% CI=1.3-1068.5;
      P=0.036), and the massive or diffuse type of tumor morphology (OR=53.5; 95%
      CI=3.0-964.2; P=0.007). CONCLUSIONS: The prognosis in patients with ruptured HCCs
      was poor with a 30-day mortality of 43.5%. The early deaths after the rupture of
      HCC were associated with elevated serum bilirubin levels, hepatic encephalopathy,
      and the massive or diffuse type of tumor morphology.

PMID- 19581768
TI  - [Clinical features of hepatic tuberculosis in biopsy-proven cases].
AB  - BACKGROUNDS/AIMS: Hepatic involvement is frequently observed in patients with
      miliary tuberculosis, but primary hepatic tuberculosis with no clinical
      extrahepatic manifestations of tuberculosis is uncommon. With the ever-increasing
      number of immunocompromised patients, it is expected that hepatic tuberculosis
      will occur more frequently. The aim of the present study was to establish the
      clinical manifestations and course of the disease. METHODS: From January 1989 to
      September 2008, 12 patients were diagnosed with hepatic tuberculosis by liver
      biopsy at Seoul National University Hospital. We retrospectively evaluated their
      clinical, laboratory, and imaging findings by medical record review. RESULTS:
      Four patients had primary hepatic tuberculosis, and eight patients had hepatic
      tuberculosis secondary to pulmonary or miliary tuberculosis. Three patients were
      immunocompromised, and six patients had no previous medical problem. An elevated
      serum level of alkaline phosphatase was the most frequently observed finding in
      laboratory tests. Imaging studies showed variable findings, including
      hepatosplenomegaly, multiple hepatic nodules, abscess formation, and even normal
      findings. Ten patients responded to antituberculosis drugs, and two cases with
      tuberculous liver abscess had persistent disease despite prolonged therapy.
      CONCLUSIONS: In patients with a protracted illness, hepatosplenomegaly and/or
      abnormal liver function tests, hepatic tuberculosis should be suspected, even in
      healthy young patients or patients with normal imaging findings. Patients with
      tuberculous abscess formation tend to respond poorly to antituberculosis therapy,
      and surgery could be considered in these patients.

PMID- 19581769
TI  - [Comparison of lamivudine-induced HBsAg loss rate according to age in children
      with chronic hepatitis B].
AB  - BACKGROUND/AIMS: The aim of this study was to establish the characteristics of
      children with hepatitis B e antigens (HBeAg) positive chronic hepatitis B who
      were cleared of hepatitis B surface antigens (HBsAg) as a result of lamivudine
      treatment. METHODS: Seventy-six children with chronic hepatitis B who were
      seropositive for HBeAg were treated with lamivudine for at least 6 months. HBeAg
      seroconversion occurred during treatment in 49 of these children, who were then
      followed up to assess their clearance of serum HBsAg. Various clinical variables
      were compared between those patients who were cleared of HBsAg and those who were
      not, including age, pretreatment serum levels of alanine aminotransferase (ALT)
      and hepatitis B virus (HBV) DNA, treatment duration, the time elapsed between
      initiation of treatment and ALT normalization, HBV DNA negativization, HBeAg
      seroconversion, and HBsAg clearance. RESULTS: HBsAg disappeared in 13 of the 49
      (26.5%) patients who experienced lamivudine-induced HBeAg seroconversion; HBsAg
      did not reappear during follow-up period (1-86 months). The time that elapsed
      between initiation of lamivudine treatment and total HBsAg clearance was 25.9+/
      27.1 months (mean+/-SD; range: 5-104 months). The age at which treatment was
      initiated was the only factor associated with HBsAg clearance. Children who were
      cleared of HBsAg were significantly younger than those who were not (5.1+/-4.3
      years vs. 7.9+/-4.9 years, respectively; P=0.006). All 13 of these patients
      eventually produced antibodies to HBsAg. CONCLUSIONS: Younger children (age <7
      years old) have a higher chance of HBsAg clearance than older children after the
      treatment of HBeAg-positive chronic hepatitis B with lamivudine.

PMID- 19581770
TI  - [Long-term clevudine therapy in nucleos(t)ide-naive and lamivudine-experienced
      patients with hepatitis B virus-related chronic liver diseases].
AB  - BACKGROUNDS/AIMS: Clevudine is an effective antiviral nucleoside analogue, but
      there are few data regarding its long-term effects, resistance, and safety. The
      aim of this study was to evaluate the long-term clinical efficacy of clevudine
      over a 1-year treatment period in nucleos(t)ide-naive and lamivudine-experienced
      chronic hepatitis B patients. METHODS: Nucleos(t)ide-naive (group A, n=196) and
      lamivudine-experienced (serum hepatitis B virus, HBV DNA >2,000 copies/mL without
      resistant mutants at the start of clevudine therapy, group B, n=75) patients were
      included in this study. Basic clinical characteristics including age, sex, the
      presence of cirrhosis, laboratory data, and hepatitis B surface antigen (HBeAg)
      positivity were similar between the two groups. Pretreatment serum levels of HBV
      DNA were 7.4 and 6.6 log(10) copies/mL (P<0.001). The mean treatment duration was
      8 months for both groups (range for group A: 3-21 months; range for group B: 3-20
      months). Genotypic analysis for resistant mutations in the reverse transcriptase
      of HBV was performed after viral breakthrough. RESULTS: After 1 year of therapy,
      75.0% and 51.9% of groups A and B, respectively, had HBV DNA levels of <2,000
      copies/mL (P=0.032), and HBeAg seroconversion rates were 16.9% and 16.7%,
      respectively. The rates of viral breakthrough at 1 year were 10.0% (8/80) and
      44.4% (12/27), respectively (P<0.001). Proven sites of mutation of HBV DNA
      polymerase in naive patients were, for example, L80I, L180M, A181V/T, M204I and
      V207I. Ten patients complained of prominent fatigue and revealed elevated serum
      levels of aspartate aminotransferase (AST) and creatine phosphokinase (CPK). Two
      of these patients presented with severe myopathy from which they recovered
      completely after quitting clevudine. CONCLUSIONS: Clevudine is one of the
      recommended first-line medicines for the treatment of chronic hepatitis B, but it
      is not free from resistance, particularly in patients with a history of previous
      lamivudine treatment, but also in naive patients. Clevudine should be avoided in
      previously lamivudine-exposed patients. In addition, reelevation of serum AST and
      CPK levels is not a rare occurrence, and close observation and follow-up tests
      are essential.

PMID- 19581771
TI  - [A case of hypervascular hyperplastic nodules mimicking hepatocellular carcinoma
      in alcoholic liver cirrhosis].
AB  - Benign hypervascular hyperplastic nodules (HHN) in liver cirrhosis are very rare.
      It is important to distinguish between regenerative nodules (hyperplastic
      nodules) and tumorous nodules (dysplastic or neoplastic nodules) in
      hepatocellular nodular lesions. The differential diagnosis between HHN and
      hepatocellular carcinoma on the basis of radiologic imaging is often difficult,
      and is clinically important when determining the therapeutic plan. Therefore,
      histological confirmation by needle biopsy sampling of the liver is necessary for
      a correct diagnosis of HHN. We report herein a case of benign HHN mimicking
      hepatocellular carcinoma in a 32-year-old male alcoholic liver cirrhosis patient
      without viral hepatitis infection.

PMID- 19581772
TI  - [A case of liver metastasis of gastric hepatoid adenocarcinoma].
AB  - We report herein a case of hepatoid adenocarcinoma of the stomach with liver
      metastasis. Gastric carcinoma generally presents as adenocarcinoma and rarely
      shows a hepatoid pattern, which can produce alpha-fetoprotein (AFP). The stomach
      is one of the common sites at which hepatoid adenocarcinoma has been detected. A
      75-year-old female patient was admitted to the hospital with a symptom of
      epigastric discomfort. Gastrofibroscopy revealed a large tumor occupying the
      greater curvature of the stomach body. The level of serum AFP was markedly
      increased. Abdominal computed tomography revealed multiple liver masses. Biopsy
      samples of the gastric lesion and liver masses finally confirmed her case as
      hepatoid adenocarcinoma in the stomach with liver metastasis. The AFP-producing
      gastric carcinoma needs special attention because it often presents with early
      liver metastasis and has a poor prognosis.

PMID- 19581773
TI  - Development of ocular myasthenia during pegylated interferon and ribavirin
      treatment for chronic hepatitis C.
AB  - A 63-year-old male experienced sudden diplopia after 9 weeks of administration of
      pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC).
      Ophthalmologic examinations showed ptosis on the right upper lid and restricted
      right eye movement without any other neurological signs. A brain imaging study
      and repetitive nerve stimulation test indicated no abnormality. The acetylcholine
      receptor antibody titer and response to acetylcholinesterase inhibitors were
      negative, and the results of thyroid function tests were normal. The patient's
      ophthalmological symptoms improved rapidly 3 weeks after discontinuation of
      pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with
      combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very
      rarely reported; therefore, we present this case with a review of the various eye
      complications of IFN therapy.

PMID- 19581775
TI  - [Epithelioid hemangioendothelioma].

PMID- 19581774
TI  - [Primary angiosarcoma of the liver].

PMID- 19581777
TI  - Bullying isn't just found on the playground.

PMID- 19581779
TI  - An appreciative inquiry approach to RN retention.

PMID- 19581780
TI  - Critical steps to prevent falls in hospitalized older patients.

PMID- 19581781
TI  - Growing clinical informatics in a multifacility environment.

PMID- 19581782
TI  - Cooler heart, better odds: induced hypothermia.

PMID- 19581784
TI  - The nurse liaison: quietly working behind the scenes.

PMID- 19581785
TI  - Professional development: endless options?

PMID- 19581786
TI  - M the magnetic pull: the nuts and bolts of Magnet site visit preparation.

PMID- 19581787
TI  - How to prevent CAUTIs.

PMID- 19581788
TI  - Hiring right for a healthy work environment.

PMID- 19581789
TI  - Optimizing span of control; implementing adjunct care programs.

PMID- 19581790
TI  - HLA-G 3' UTR haplotypes and HIV vertical transmission.
AB  - We evaluated the possible association of human leukocyte antigen-G (HLA-G)
      3777G>C and 14-bp deletion/insertion (D/I) polymorphisms haplotypes and combined
      genotypes with perinatal HIV transmission in Brazilian children. The 3777G>C
      polymorphism alone has no effect on HIV vertical transmission but, when linked
      with the D allele, exerts a positive role in the protection. Indeed, we
      identified the DC HLA-G haplotype as significantly associated with a protective
      effect towards HIV vertical transmission.

PMID- 19581791
TI  - HIV sensitivity to neutralization is determined by target and virus producer cell
      properties.
AB  - OBJECTIVE: Using clinical isolates from a recent passive immunization trial with
      antibody 2G12, we probed the capacity of frequently used neutralization formats -
      the primary peripheral blood mononuclear cell (PBMC)-based and the TZM-bl cell
      based assay systems - to predict in-vivo activity of 2G12. DESIGN: Antibodies and
      entry inhibitors of established efficacy were used to neutralize HIV-1 isolates
      in different in-vitro assay setups. METHODS: Single round infection with Env
      pseudotyped and multiple round infection with replication-competent virus was
      studied on PBMCs and a variety of engineered cell lines. RESULTS: Six out of 12
      isolates with high sensitivity to 2G12 in the replication-competent PBMC assay
      lacked sensitivity to the monoclonal antibody in the env-pseudotype TZM-bl assay.
      Outcome of passive immunization with 2G12 corroborated the PBMC-assay in-vitro
      data, as escape mutations to 2G12 emerged, proving the monoclonal antibody's
      impact on HIV in vivo. Failure to inhibit pseudotype infection of TZM-bl was not
      due to sequence differences or the pseudotype infection per se, as infection of
      PBMCs with the identical pseudotyped viruses was sensitive to 2G12 inhibition.
      Similar shifts in efficacy, though less extreme, were noted for other
      neutralizing antibodies and inhibitors. Exploration of causes for the observed
      differences between assay systems revealed that both target cell and virus
      producer properties influence sensitivity of virus entry to inhibition.
      CONCLUSION: Our observation that neutralization assay systems employing
      engineered reporter cell lines can miss in-vivo relevant neutralizing activities
      strongly argues that preclinical assessment should not be restricted to a single
      assay type.

PMID- 19581792
TI  - Angiosarcoma of the breast: a rare clinicopathological entity.
AB  - OBJECTIVES: Angiosarcoma is a rare subtype of sarcoma that usually arises after
      radiation therapy for primary breast cancer. Primary sarcomas of the breast are
      rare entities and account for less than 1% of all malignant breast neoplasms. We
      examine our institutional experience with angiosarcomas of the breast that were
      diagnosed and treated between 1996 and 2007. METHODS: To conduct a retrospective
      review, all female patients with a diagnosis of angiosarcoma of the breast were
      identified from our pathology database. Their hospital records were retrieved to
      gather information on treatment, tumor response, failure, and survival. RESULTS:
      A total of 8 patients were identified who had a histologically confirmed
      diagnosis of angiosarcoma of the breast. Median age was 70.3 years at diagnosis
      (range, 35.6-85.7 years). Seven (87%) patients had a history of prior radiation
      to the breast, whereas 1 (13%) had primary angiosarcoma. The median overall
      survival was 37.4 months (8.7-92.8 months) and relapse-free survival was 17.9
      months (2.5-69.4 months). CONCLUSIONS: Even though angiosarcomas are rare
      neoplasms, they are increasingly recognized as the result of more breast
      conserving therapy. High clinical suspicion and MRI may contribute to early
      diagnosis but a biopsy is always necessary to confirm it. These tumors tend to
      behave aggressively and require a multidisciplinary approach to improve the
      outcome.

PMID- 19581793
TI  - Triweekly oxaliplatin plus oral capecitabine as first-line chemotherapy in
      elderly patients with advanced gastric cancer.
AB  - OBJECTIVES: To investigate the efficacy and safety of oxaliplatin plus oral
      capecitabine (XELOX) as first-line chemotherapy in elderly patients with advanced
      gastric cancer (AGC). PATIENTS AND METHODS: Forty-four previously untreated
      patients with AGC aged 70 or older participated in the study. They received
      oxaliplatin 130 mg/m(2) as 2-hour intravenous infusion on day 1 and oral
      capecitabine 1000 mg/m(2) twice daily on days 1 to 14 every 3 weeks XELOX.
      RESULTS: All patients were assessable for toxicity and 41 patients for response.
      Median age was 75 years (range, 70-83). In total, 215 cycles of XELOX were
      delivered. The response rate according to Response Evaluation Criteria in Solid
      Tumors was 51.2% (95% confidence interval [CI]: 35.9%-66.5%), with 2 complete
      responses, 19 partial responses, 11 stable diseases, and 9 progressions. At 9.5
      months median follow-up, median time to progression and overall survival were 5.6
      (95% CI: 4.6-6.6) and 9.8 months (95% CI: 7.4-12.2), respectively. Toxicities
      were generally mild. Grades 3 to 4 adverse events included: neutropenia (6
      patients, 13.6%), diarrhea (6 patients, 13.6%), thrombocytopenia (5 patients,
      11.4%), hand-foot syndrome (4 patients, 9.1%), nausea and vomiting (2 patients,
      4.5%), and anemia (1 patient, 2.3%). Neutropenic fever occurred in 2 patients.
      There was no treatment-related death. CONCLUSIONS: XELOX is active and well
      tolerated as first-line chemotherapy for elderly patients with AGC. Given its
      ease of administration, it represents a good therapeutic option in the elderly.

PMID- 19581794
TI  - Radiation treatment interruptions greater than one week and low hemoglobin levels
      (12 g/dL) are predictors of local regional failure after definitive concurrent
      chemotherapy and intensity-modulated radiation therapy for squamous cell
      carcinoma of the head and neck.
AB  - PURPOSE: To determine whether baseline hemoglobin level and radiation treatment
      interruptions predict for loco-regional failure after intensity-modulated
      radiation therapy (IMRT) with concurrent chemotherapy for definitive treatment of
      squamous cell carcinoma of the head and neck (SCCHN). METHODS: This retrospective
      review identified 78 consecutive patients treated with definitive concurrent
      chemoradiation for SCCHN. Patients were treated with IMRT to 70 Gy in 35 daily
      fractions to the high-dose target volume and 56 Gy to the elective target volume.
      RESULTS: Median age of the cohort was 62 (37-81). Median follow-up was 12 months.
      Tumor sites included: oropharynx (54%), larynx (36%), oral cavity (5%), and
      hypopharynx (5%). Fifteen of 78 patients (19%) experienced loco-regional failure.
      These included: 6 primary site failures, 5 regional failures, and 4 failures in
      both the primary site and regional lymph nodes. All but one failure occurred in
      the high-dose target volume. Only duration of radiation treatment and baseline
      hemoglobin levels were significant predictors of local control. Loco-regional
      failure occurred in 6 of 13 patients (46%) with radiation treatment interruptions
      (>1 week) versus 9 of 65 patients (14%) completing radiation therapy without
      interruption (P = 0.0148). Loco-regional failure occurred in 7 of 19 patients
      (37%) whose pretreatment hemoglobin level was <12 g/dL compared with 8 of 59
      patients (14%) with hemoglobin levels > or = 12 (P = 0.042). CONCLUSION: Overall
      radiation treatment time and pretreatment hemoglobin level were significant
      predictors for loco-regional failure after definitive concurrent chemotherapy and
      IMRT for SCCHN.

PMID- 19581795
TI  - Renal cell carcinoma metastasis to focal nodular hyperplasia focus on liver in a
      patient with Von Hippel-Lindau disease.
AB  - Von Hippel-Lindau disease is an autosomal dominant disorder occurring in 1 of
      36,000 births and associated with various tumors and cysts in the central nervous
      system and other visceral organs. At present, metastasis from renal cell
      carcinoma (RCC) and neurologic complications are the most common causes of death
      from Von Hippel-Lindau disease. We report a case of Von Hippel-Lindau disease
      diagnosed during a screening and was found to have metastasis of RCC to a focal
      nodular hyperplasia lesion on the liver. In the literature, misdiagnosis of
      benign liver lesions as metastases of RCC has been reported, but there has not
      been a case reported to have a metastasis of RCC within a benign liver lesion. To
      our knowledge, this is the first case of RCC metastasis to a benign lesion of the
      liver.

PMID- 19581796
TI  - Postirradiation Klebsiella pneumoniae-associated necrotizing fasciitis in the
      western hemisphere: a rare but life-threatening clinical entity.
AB  - Necrotizing fasciitis (NF) caused by Klebsiella spp. is a unique entity,
      particularly, in Asia, where virulent strains of Klebsiella predominate. It is
      now clear that Klebsiella spp. are capable of causing NF either isolated or in
      the context of disseminated disease. We present a unique case of NF caused by
      Klebsiella pneumoniae in the Western hemisphere after radiotherapy in a
      hospitalized patient with significant comorbidities. Physicians should be aware
      of nosocomially acquired K. pneumoniae fasciitis after radiotherapy in the
      setting of chronic comorbidities, such as diabetes and malignancy. Early
      diagnosis, surgical intervention, and appropriate empirical antibiotics are
      essential for a favorable outcome in such rare but life-threatening cases of NF.

PMID- 19581797
TI  - Pamidronate-induced kidney injury in a patient with metastatic breast cancer.
AB  - The American Society of Clinical Oncology recommends bisphosphonate use, such as
      intravenous pamidronate, for women with breast cancer who have radiographic
      evidence of bone destruction. However, pamidronate therapy has been associated
      with the development of the nephrotic syndrome. This renal abnormality has been
      posited to be due to a number of different mechanisms, including collapsing focal
      segmental glomerulosclerosis (FSGS). We present one such case of a patient who
      developed collapsing FSGS with nephrotic-range proteinuria after treatment with
      pamidronate for osteolytic bone metastases from an infiltrating ductal carcinoma
      of the breast. A possible mechanism of this kidney injury is mitochondrial
      apoptosis in podocytes and/or proximal tubular cells, which has been shown to
      occur in a dose-dependent fashion in experimental models. Renal prognosis is very
      poor if collapsing FSGS develops. Thus, prevention or early detection rather than
      effective therapy should be the primary consideration.

PMID- 19581798
TI  - Interaction of ionizing radiation and ZRBA1, a mixed EGFR/DNA-targeting molecule.
AB  - ZRBA1 is a molecule termed 'combi-molecule' designed to induce DNA-alkylating
      lesions and to block epidermal growth factor receptor (EGFR) tyrosine kinase.
      Owing to its ability to downregulate the EGFR tyrosine kinase-mediated
      antiapoptotic signaling and DNA repair proteins, we inferred that it could
      significantly sensitize cells to ionizing radiation. Using the MDA-MB-468 human
      breast cancer cell line in which ZRBA1 has already been reported to induce
      significant EGFR/DNA-targeting potency, the results showed that: (i) concurrent
      administration of ZRBA1 and 4 Gy radiation led to a significant decrease in cell
      viability, (ii) the greater efficacy of the combination was sequential, being
      limited to conditions wherein the drug was administered concurrently with
      radiation or before radiation, and (iii) the efficacy enhancement of the
      combination was further confirmed by clonogenic assays from which a dose
      enhancement factor of 1.34 could be observed at survival fraction of 0.01. Flow
      cytometric analysis showed significant enhancement of cell cycle arrest in G2/M
      (P<0.046, irradiated cells vs. cells treated with ZRBA1 and radiation) and
      increased apoptosis when ZRBA1 was combined with radiation. Likewise, significant
      levels of double-strand breaks were observed for the combination, as determined
      by neutral comet assay (P<0.045, irradiated cells vs. cells treated with ZRBA1
      and radiation). These results in toto suggest that the superior efficacy of the
      ZRBA1 plus radiation combination may be secondary to the ability of ZRBA1 to
      arrest the cells in G2/M, a cell cycle phase in which tumor cells are sensitive
      to radiation. Furthermore, the increased levels of DNA damage, combined with the
      concomitant downregulation of EGFR-mediated signaling by ZRBA1, may account for
      the significant levels of cell killing induced by the combination.

PMID- 19581800
TI  - Carbon monoxide-releasing molecule-2 decreases fibrinolysis in human plasma.
AB  - Carbon monoxide, derived from carbon monoxide-releasing molecules, has been
      recently demonstrated to enhance the velocity of formation and strength of plasma
      thrombi. We tested the hypothesis that carbon monoxide-releasing molecule-2 would
      modulate fibrinolysis of plasma thrombi. Normal plasma was exposed to 0, 25, 50,
      100 or 200 micromol/l carbon monoxide-releasing molecule-2, with coagulation
      activated with tissue factor and fibrinolysis initiated with tissue-type
      plasminogen activator. Additional experiments utilized factor XIII, plasminogen
      activator inhibitor-1, thrombin activatable fibrinolysis inhibitor or alpha2
      antiplasmin-deficient plasmas. Thrombus growth/disintegration kinetics was
      monitored with thrombelastography. Carbon monoxide-releasing molecule-2, in a
      concentration-dependent fashion, increased the velocity of thrombus formation and
      strength, and markedly attenuated fibrinolysis in normal plasma. In factor XIII
      deficient plasma, carbon monoxide-releasing molecule-2 mediated effects on
      thrombus growth/disintegration kinetics were similar to that seen with normal
      plasma; however, carbon monoxide-releasing molecule-2 had a less marked effect on
      thrombus growth/disintegration in both plasminogen activator inhibitor-1 and
      thrombin activatable fibrinolysis inhibitor-deficient plasma, with even less
      carbon monoxide-releasing molecule-2-mediated effects noted in alpha2-antiplasmin
      deficient plasma. Carbon monoxide-releasing molecule-2 attenuated fibrinolysis by
      enhancing the velocity of clot growth and strength while augmenting the effects
      of plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor
      and alpha2-antiplasmin. These findings serve as the rationale for further
      investigations to determine if carbon monoxide-releasing molecules could be
      utilized as hemostatic agents.

PMID- 19581799
TI  - Central urocortin 3 administration decreases limited-access ethanol intake in
      nondependent mice.
AB  - Stress and alcohol abuse are co-related. Acute alcohol is anxiolytic and stress
      is cited as a factor in relapse to alcohol use. A primary mediator of the stress
      response is the neuropeptide corticotropin-releasing factor (CRF). The CRF family
      of endogenous ligands includes urocortin 3 (Ucn 3), which binds selectively to
      the CRF type 2 receptor and has been implicated in ethanol consumption in
      dependent and withdrawing rats. The objective of this study was to examine the
      effect of Ucn 3, delivered centrally to nondependent mice, on limited-access
      ethanol consumption. Adult C57BL/6J mice were trained to self-administer 10%
      ethanol during daily, 2-h limited-access sessions, using lickometers to assess
      drinking patterns for both ethanol and water. Sterile saline or 0.3, 1, or 3 nmol
      of Ucn 3 was microinjected into the lateral ventricle immediately before the
      limited-access session in a within-subjects design. There was a significant
      decrease in ethanol (both ml and g/kg), but not water, intake following Ucn 3
      treatment, explained by a change in size of the largest lick run. Food intake at
      both 2 h and 24 h after injection was statistically unaffected by Ucn 3
      administration. These results establish a role for CRF type 2 receptors in a
      nondependent mouse model of ethanol self-administration.

PMID- 19581801
TI  - Thromboelastometry in patients with severe sepsis and disseminated intravascular
      coagulation.
AB  - Severe sepsis induces coagulopathy, which may lead to disseminated intravascular
      coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation
      monitor, which has been validated in human endotoxemia model. We assessed
      thromboelastometry in severe sepsis and overt DIC and investigated its
      applicability in differentiating sepsis-related coagulation disturbances.
      Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays
      were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria
      of overt DIC on admission. Ten healthy persons served as controls. Coagulation
      parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot
      firmness (MCF) and lysis index at 60 min, were registered. In patients with overt
      DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls
      and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT
      184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P < 0.01
      for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM
      and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034,
      respectively). Receiver operating characteristic curves showed that MCF, CFT and
      alpha angle discriminated patients with overt DIC moderately (area under curve
      0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation
      assays showed progressively worsening coagulopathy from controls to septic
      patients without DIC and further to those with overt DIC. We conclude that
      thromboelastometry may be a valuable tool in assessing whole blood coagulation
      capacity in patients with severe sepsis with and without overt DIC.

PMID- 19581802
TI  - Pulse pressure and nocturnal fall in blood pressure are predictors of vascular,
      cardiac and renal target organ damage in hypertensive patients (LOD-RISK study).
AB  - OBJECTIVES: To analyse the relationship between various parameters derived from
      ambulatory blood pressure monitoring (ABPM) and vascular, cardiac and renal
      target organ damage. METHODS: A cross-sectional, descriptive study. It included
      353 patients with short-term or recently diagnosed hypertension. PRIMARY
      MEASUREMENTS: ABPM, carotid intima-media thickness (IMT), Cornell voltage
      duration product (Cornell VDP), glomerular filtration rate and albumin/creatinine
      ratio to assess vascular, cardiac and renal damage. RESULTS: Two hundred and
      twenty-three patients (63.2%) were males, aged 56.12+/-11.21 years. The nocturnal
      fall in blood pressure was 11.33+/-8.41, with a dipper pattern in 49.0% (173),
      nondipper in 30.3% (107), extreme dipper in 12.7% (45) and riser in 7.9% (28).
      The IMT was lower in the extreme dipper (0.716+/-0.096 mm) and better in the
      riser pattern (0.794+/-0.122 mm) (P<0.05). The Cornell VDP and albumin/creatinine
      ratio were higher in the riser pattern (1818.94+/-1798.63 mm/ms and 140.78+/
      366.38 mg/g, respectively) than in the other patterns. In the multivariate
      analysis after adjusting for age, sex and antihypertensive treatment, with IMT as
      dependent variable the 24-h pulse pressure (beta = 0.003), with Cornell VDP the
      rest pulse pressure (beta = 12.04), and with the albumin/creatinine ratio the
      percentage of nocturnal fall in systolic blood pressure (beta = -3.59), the rest
      heart rate (beta = 1.83) and the standard deviation of 24-h systolic blood
      pressure (beta = 5.30) remain within the equation. CONCLUSION: The estimated
      pulse pressure with ABPM is a predictor of vascular and cardiac organ damage. The
      nocturnal fall and the standard deviation in 24-h systolic blood pressure
      measured with the ABPM is a predictor of renal damage.

PMID- 19581803
TI  - Implementation of a mandatory checklist of protocols and objectives improves
      compliance with a wide range of evidence-based intensive care unit practices.
AB  - OBJECTIVE: To determine a) if a checklist covering a diverse group of intensive
      care unit protocols and objectives would improve clinician consideration of these
      domains and b) if improved consideration would change practice patterns. DESIGN:
      Pre- and post observational study. SETTING: A 24-bed surgical/burn/trauma
      intensive care unit in a teaching hospital. PATIENTS: A total of 1399 patients
      admitted between June 2006 and May 2007. INTERVENTIONS: The first component of
      the study evaluated whether mandating verbal review of a checklist covering 14
      intensive care unit best practices altered verbal consideration of these domains.
      Evaluation was performed using real-time bedside audits on morning rounds. The
      second component evaluated whether the checklist altered implementation of these
      domains by changing practice patterns. Evaluation was performed by analyzing data
      from the Project IMPACT database after patients left the intensive care unit.
      MEASUREMENTS AND MAIN RESULTS: Verbal consideration of evaluable domains improved
      from 90.9% (530/583) to 99.7% (669/671, p < .0001) after verbal review of the
      checklist was mandated. Bedside consideration improved on the use of deep venous
      thrombosis prophylaxis (p < .05), stress ulcer prophylaxis (p < .01), oral care
      for ventilated patients (p < 0.01), electrolyte repletion (p < .01), initiation
      of physical therapy (p < .05), and documentation of restraint orders (p < .0001).
      Mandatory verbal review of the checklist resulted in a greater than two-fold
      increase in transferring patients out of the intensive care unit on telemetry
      (16% vs. 35%, p < .0001) and initiation of physical therapy (28% vs. 42%, p <
      .0001) compared with baseline practice. CONCLUSIONS: A mandatory verbal review of
      a checklist covering a wide range of objectives and goals at each patient's
      bedside is an effective method to improve both consideration and implementation
      of intensive care unit best practices. A bedside checklist is a simple, cost
      effective method to prevent errors of omission in basic domains of intensive care
      unit management that might otherwise be forgotten in the setting of more urgent
      care requirements.

PMID- 19581804
TI  - Regional techniques and outcome: what is the evidence?
AB  - PURPOSE OF REVIEW: Despite some controversy regarding the strength of the
      available data, the use of regional anesthesia and analgesia does provide
      improvement in patient outcomes. Although the majority of available data have
      examined the effect of epidural anesthesia and analgesia on patient outcomes, an
      increasing number of studies recently have investigated the effect of peripheral
      regional techniques on patient outcomes. RECENT FINDINGS: Data generally indicate
      that the perioperative use of regional anesthesia and analgesia may be associated
      with improvement in both major (e.g. mortality, major morbidity) outcomes and
      rehabilitation. The majority of evidence favors an ability of epidural analgesia
      to reduce postoperative cardiovascular and pulmonary complications and there is
      also consistent evidence that epidural analgesia with local anesthetics is
      associated with faster resolution of postoperative ileus after major abdominal
      surgery. Overall, regional analgesic techniques provide statistically superior
      analgesia compared with systemic opioids. SUMMARY: Perioperative use of regional
      analgesic techniques may provide improvement in conventional outcomes, although
      the benefit appears to be limited to high-risk patients and those undergoing high
      risk procedures. The benefits conferred by perioperative regional anesthetic
      techniques need to be weighed against any potential risks and this should be
      assessed on an individual basis.

PMID- 19581805
TI  - Lipid resuscitation for local anesthetic toxicity: is it really lifesaving?
AB  - PURPOSE OF REVIEW: Laboratory studies and clinical reports have led to the
      acceptance of lipid emulsion as an effective treatment of local anesthetic
      induced cardiac arrest. This review discusses subsequent clinical reports,
      relevant laboratory studies and topics for further research. RECENT FINDINGS:
      Case reports have confirmed the efficacy of lipid resuscitation for local
      anesthetic systemic toxicity. Furthermore, lipid emulsion has been used with
      apparent success early in the spectrum of local anesthetic systemic toxicity to
      preempt cardiac arrest. The role of lipid emulsion has expanded to treatment of
      cardiac toxicity due to other lipophilic drugs. This appears to have an
      acceptable safety profile, although elevated amylase has been reported.
      Laboratory investigations in animals suggest that concomitant hypoxemia hinders
      resuscitation attempts, and that epinephrine and vasopressin are more likely to
      be associated with poor outcomes than lipid. SUMMARY: Lipid emulsion infusion
      appears to be an effective treatment for cardiac toxicity induced by lipophilic
      medications. Given the difficulties of performing clinical trials, further
      laboratory investigation and clinical correlation are needed to better define its
      role in resuscitation.

PMID- 19581807
TI  - Early language development in children with profound hearing loss fitted with a
      device at a young age: part II--content of the first lexicon.
AB  - OBJECTIVE: Lexical content is commonly understood to refer to the various
      categories of words that children produce and has been studied extensively in
      children with normal hearing. Unlike the hearing child, however, little is known
      about the word categories that make up the first lexicon of children with hearing
      loss (HL). Knowledge of the first lexicon is increasingly important, as infants
      with HL are now being detected through universal newborn hearing screening
      programs and fitted with hearing aids and cochlear implants in before 12 months
      of age. For these children, emergence of the first spoken words is a major
      milestone eagerly awaited by parents and one of the first verbal language goals
      of teachers and therapists working with such children. The purpose of this study
      was to evaluate the lexical content of the first 50 and 100 words produced by
      children with HL and to contrast this with that of a group of hearing children.
      DESIGN: Lexical content was compared in two groups of children: one group
      composed of 24 participants with severe profound or profound HL and a second
      group composed of 16 participants with normal hearing. Twenty-three participants
      in the HL group were fitted with a cochlear implant and one with bilateral
      hearing aids. All were "switched on" or fitted before 30 months of age. The Diary
      of Early Language (Di-EL) was used to collect a 100-word lexicon from each
      participant. All single word and frozen phrase data from each child's Di-EL were
      allocated to 1 of 15 word types grouped into four word categories (noun,
      predicate, grammatical, and paralexical), and the results were compared for both
      groups. RESULTS: The hearing and HL groups showed similar distributions of word
      categories, with nouns constituting the largest portion of the lexicon followed
      by predicates and paralexicals. Grammaticals made up the smallest portion of the
      lexicon. However, several significant differences were evident between the two
      groups. In both the 50- and 100-word lexicons, the hearing group used
      proportionately more nouns, fewer predicates, more common nouns, and fewer
      onomatopoeic words compared with the HL group. Further, more participants in the
      hearing group used grammatical word types other than adverbs (including pronouns)
      compared with the HL group. CONCLUSION: Overall, lexical content of the HL group
      was similar to that of the hearing group for both the 50- and 100-word lexicons,
      although some differences in proportional use were noted across word categories
      and types. It is suggested that differences in the quantity and diversity of
      language experienced by children with normal hearing compared with those with HL,
      together with differences in the input they receive, might in part explain these
      differences. The effect of quality of speech input and therapy method on the
      emerging lexicon and subsequent language development will be particularly
      important in informing appropriate intervention strategies for children with HL.

PMID- 19581808
TI  - Breast cancer screening participation among Turks and Moroccans in the
      Netherlands: exploring reasons for nonattendance.
AB  - In the Netherlands, attendance rates for breast cancer screening are much lower
      among Dutch women born in Turkey and Morocco than they are among native Dutch.
      The reasons for this trend are not yet known. Currently, mortality and incidence
      rates for these migrant groups are much lower than those of the native
      population. However, studies show convergence towards the rates of the native
      Dutch population. We therefore performed a narrative literature review to study
      the reasons behind the low participation rate for breast cancer screening among
      Turkish and Moroccan women in the Netherlands. No truly relevant research on this
      topic was available. Information acquired from articles only applicable to
      certain areas of the research question showed that reasons pertaining to lack of
      awareness and knowledge, organizational issues and socio-cultural aspects are
      most likely to be responsible for the low attendance. To increase attendance
      rates, more research is needed to obtain insight into these aspects and into the
      reasons given by Turkish and Moroccan women.

PMID- 19581806
TI  - The enigmatic role of mast cells in dominant tolerance.
AB  - PURPOSE OF REVIEW: The role of regulatory T cells (Treg) in peripheral tolerance
      has been studied extensively in transplantation research. Recently, mast cells
      have been shown to play an indispensable role in allograft tolerance. The purpose
      of this review is to inform the reader on the current standings of the role of
      mast cells in dominant tolerance with an emphasis on the interaction of mast
      cells with Treg. RECENT FINDINGS: Mast cells are required to sustain peripheral
      tolerance via Treg. Treg can stabilize mast cells degranulation by contact
      dependent mechanisms through the interaction of OX40 and its ligand OX40L, and by
      production of soluble factors, such as interleukin-10 and transforming growth
      factor-beta. Conversely, the activation and subsequent degranulation of mast
      cells break peripheral tolerance. SUMMARY: Both mast cells and Treg are needed to
      create a local immunosuppressive environment in the transplant. Treg are not only
      necessary to suppress effector T-cell responses but also to stabilize mast cells.
      Mast cells in return could contribute to the immunosuppressive state by release
      of transforming growth factor-beta, interleukin-10 and specific proteases.
      However, the molecular basis for mast cells control of Treg suppression in organ
      transplantation is still unresolved.

PMID- 19581809
TI  - Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving
      the colon: a prospective study.
AB  - OBJECTIVES: Fecal calprotectin seems to have a diagnostic precision in predicting
      relapse in quiescent ulcerative colitis patients. However, the data remain
      controversial in Crohn's disease. The aim of this study was to prospectively
      evaluate the role of fecal calprotectin as a predictive marker for 1-year follow
      up in patients with asymptomatic Crohn's disease. METHODS: Fifty-three Crohn's
      disease patients in clinical remission were consecutively included providing at
      the beginning of the study a single stool sample as well as a blood sample and
      regularly followed-up for 12 months. Fecal calprotectin level was measured using
      a commercially available enzyme-linked immunoassay. RESULTS: Among 53 patients,
      10 (18.9%) developed clinical relapse during the 12-month follow-up period.
      Median fecal calprotectin level was significantly higher in relapse group
      patients compared with that in nonrelapse group (380.5 vs. 155 microg/g,
      P<0.001). With a cutoff value of 340 microg/g fecal calprotectin gave sensitivity
      of 80% and specificity of 90.7% in predicting clinical relapse. Fecal
      calprotectin level greater that 340 microg/g gave an 18-fold higher risk to
      develop relapse (log rank P<0.001) and was found to be an independent predictive
      factor of relapse (P=0.02). CONCLUSION: Fecal calprotectin seems to be a reliable
      marker of relapse in quiescent Crohn's disease patients.

PMID- 19581810
TI  - Costs and risks in the management of patients with gastric acid hypersecretion.
AB  - GOALS: To define both risks and costs of optimal care of patients with gastric
      acid hypersecretion. BACKGROUND: The management of Zollinger-Ellison syndrome and
      other gastric acid hypersecretory disorders remains challenging. The optimal
      strategy for follow-up including gastric acid analysis, laboratory studies, and
      endoscopy is unknown but important given the potential complications from
      uncontrolled acid secretion. STUDY: Over the last 18 years, patients with gastric
      acid hypersecretory disorders have been followed prospectively with gastric acid
      analysis and endoscopy titrating oral lansoprazole and evaluating for
      complications. Protocol driven charges were calculated using the most recent
      information available. RESULTS: After 1 year of treatment optimization, 19 of 67
      patients had 43 relapses, (once only in 10 patients). Risk markers for relapse
      included: (1) antrectomy, 67% relapsed versus 21% in unoperated patients; (2)
      basal acid output >5 mmol/h (risk=5.17); and (3) poor compliance. On treatment,
      79% of 58 intact patients (excluding antrectomy) were lesion-free; 11% had only 1
      relapse. Thus 90% were well managed with optimized lansoprazole alone. Protocol
      driven charges exceeded $25,000 the first year and $7000 annually thereafter.
      CONCLUSIONS: Relapse is infrequent and generally mild with acid secreting status
      closely monitored. The ideal strategy to balance costs and testing awaits further
      study.

PMID- 19581811
TI  - Moxifloxacin associated vanishing bile duct syndrome.

PMID- 19581812
TI  - Assessment of liver fibrosis and steatosis in PBC with FibroScan, MRI, MR
      spectroscopy, and serum markers.
AB  - BACKGROUND: In recent years noninvasive methods have been evaluated for the
      assessment of liver fibrosis predominantly in patients with viral hepatitis. In
      this study, transient elastography (FibroScan), magnetic resonance imaging (MRI),
      magnetic resonance (MR)-spectroscopy, and serum markers were compared in patients
      with primary biliary cirrhosis (PBC) for the assessment of liver fibrosis and
      steatosis. METHODS: Forty-five patients with PBC and histologic assessment of
      liver fibrosis received transient elastography and examinations for serum markers
      of fibrosis and steatosis. In addition, 41 out of 45 patients received contrast
      enhanced MRI and 38 out of 45 patients received proton MR-spectroscopy. RESULTS:
      The adjusted accuracy (area under the receiver operating characteristic) for the
      diagnosis of histologic-stage > or = II for FibroScan, MRI-contrast enhancement
      and Forns index was 80%, 83%, and 69%, and for the diagnosis of liver cirrhosis
      95%, 91%, and 94%, respectively. No correlation of histologic-stage was observed
      for FibroTest and AST to platelet ratio index. Histologic steatosis significantly
      correlated with body mass index (r=0.46), the SteatoTest (r=0.39), homeostasis
      model assessment of insulin resistance (r=0.46), and MR-spectroscopy (r=-0.76).
      The accuracy for the diagnosis of histologic steatosis was best with MR
      spectroscopy (88%). CONCLUSIONS: Contrast-enhanced MRI and FibroScan can be used
      with comparable results for the assessment of liver fibrosis in patients with PBC
      and seem to supplement each other. MR-spectroscopy represents the best method for
      highly accurate noninvasive measurement of liver steatosis.

PMID- 19581813
TI  - Long term follow-up and outcome of liver transplantation for alcoholic liver
      disease: a single center case-control study.
AB  - BACKGROUND: Alcoholic liver cirrhosis (ALC) is a leading indication for
      orthotopic liver transplantation (OLT). GOALS: To investigate the long-term
      outcome of OLT for ALC compared with patients transplanted for hepatitis C virus
      (HCV) infection. STUDY: From 1987 to 2001, 49 OLT were performed for ALC and 173
      for HCV. From these contemporary groups we matched 1:2 ALC patients (cases) to 98
      HCV (controls). The following variables were analyzed: survival,
      retransplantation, rejection, primary nonfunction, infections, de novo tumors,
      cardiovascular and neurologic complications, and alcoholic recurrence. RESULTS:
      Actuarial survival rate at 9 years was comparable for cases and controls.
      Actuarial graft survival rate at 9 years was significantly higher in cases (78%
      vs. 60%; P=0.026). The retransplantation rate was higher in controls (21% vs. 4%;
      P=0.007). Post-OLT complications were not significantly different. The alcoholic
      recidivism rate was 28% without influence on patients or graft survival, whereas
      relapse of HCV caused the majority of death in controls (30%; P=0.042). At
      multivariate analysis retransplantation was the only predictor of patient
      survival (odds ratio: 4.35; 95% confidence interval: 2.16-8.74; P<0.001), whereas
      HCV was associated with a 2-fold probability of graft failure (odds ratio: 1.97;
      95% confidence interval: 1.02-3.81; P=0.032). CONCLUSIONS: The long-term outcome
      of OLT for ALC is comparable to that for HCV, even if graft survival is
      significantly better among ALC. These data support ALC as an excellent indication
      for OLT.

PMID- 19581814
TI  - Infant feeding practices and associated factors through the first 9 months of
      life in Bavaria, Germany.
AB  - OBJECTIVES: To investigate infant feeding and breast-feeding practices during the
      first 9 months of life in Bavaria, Germany, in relation to recommendations and to
      identify factors associated with early feeding of semisolid food. MATERIALS AND
      METHODS: Data from 3103 infants throughout Bavaria, Germany, were collected in a
      prospective cohort study. Questionnaires were administered at the age of 6 days,
      and 2, 4, 6, and 9 months. RESULTS: There was a considerable variety concerning
      the time when complementary feeding was introduced. Only 16.4% of the infants ate
      solid/semisolid food before the age of 5 months. Most of the infants received as
      their first solid food a mash of vegetable, meat, and potato. Compared to
      national guidelines fluids were introduced early. More than 37% of the breast-fed
      infants received additional fluids/formula. The strongest risk factor associated
      with complementary feeding before the fifth month was breast-feeding duration of
      less than 4 months (any breast-feeding) with an odds ratio of 8.57 (95%
      confidence interval 6.16-11.94). Other factors were low level of education, young
      age of the mother, smoking habit of the mother, and mother not being born in
      Germany. CONCLUSIONS: Further improvements in nutrition of infants may be
      achieved in 2 ways: promotion of breast-feeding according to current
      recommendations and better counselling on the correct timing of introduction of
      semisolid food-especially for parents of not- or short-time breast-fed babies and
      focused on young mothers with low levels of education.

PMID- 19581815
TI  - Water-immersion technique during standard upper endoscopy may be useful to drive
      the biopsy sampling of duodenal mucosa in children with celiac disease.
AB  - OBJECTIVE: To evaluate the accuracy of the water-immersion technique during upper
      endoscopy in recognizing the duodenal villous pattern in a series of children who
      were undergoing endoscopy to obtain duodenal biopsy for histological analysis.
      MATERIALS AND METHODS: The water-immersion technique was performed in 19
      children. Endoscopic findings were compared with histology. Results were assessed
      on per biopsy analysis and per patient analysis, taking into account the worst
      endoscopic finding in each patient and correlating it with the worst histological
      diagnosis. RESULTS: Per biopsy analysis: A total of 57 biopsy specimens were
      obtained and assessed. The endoscopic duodenal investigation correctly identified
      53 areas (93%), which corresponded to histology, giving it an accuracy rate of
      93%. Per patient analysis: The worst histology of the duodenal bulb was predicted
      by endoscopy in 18 of the 19 enrolled patients (95%), whereas the worst
      histopathological lesion of the second portion of the duodenum was recognized in
      100% of cases. On the whole, therefore, the endoscopist suggested a diagnosis of
      celiac disease in 11 patients, with both positive and negative predictive values
      of 100%. CONCLUSIONS: The water-immersion technique during upper endoscopy is
      highly accurate in recognizing the duodenal villous pattern in subjects who need
      a duodenal investigation. Our findings encourage a cost-saving and patient
      retaining approach to the diagnosis of celiac disease by driving biopsy and
      reducing the number of duodenal samplings.

PMID- 19581816
TI  - Technical limitations in detection of gastroesophageal reflux in neonates.
AB  - OBJECTIVE: Characterize the incidence and possible etiologies of acid reflux
      events detected by pH and not identified by multiple intraluminal impedance (MII)
      monitoring. MATERIALS AND METHODS: Acid reflux events detected by pH but not
      identified by MII (pH-only) were documented in 80 preterm and 39 term infants.
      Reasons for failure of MII to detect these events were classified as failure to
      meet MII scoring criteria, presence of an air bolus, technical artifact, and no
      change in impedance. Events with no change in impedance were stratified to low
      impedance throughout the study (possible esophageal inflammation), transient
      decrease in pre-event impedance (presence of refluxate), occurrence <30 seconds
      of a preceding event, and no explanation. RESULTS: A total of 2572 events were
      detected by pH, with 59% of events not identified by MII. A higher incidence of
      pH-only events occurred in preterm versus term infants (54 +/- 27% versus 42 +/-
      23%, P = .025, respectively). Thirteen percent of pH-only events were missed due
      to MII scoring criteria, 12% due to technical artifact, 11% due to an air bolus,
      and 64% had no change in impedance. Of the 978 events with no change in
      impedance, 154 were associated with low impedance throughout the study, 430 with
      a transient decrease in pre-event impedance, and 175 were preceded by a reflux
      episode within 30 seconds. CONCLUSIONS: There was a high incidence of acid reflux
      events detected by pH but not identified by MII. This occurred more often in the
      least mature infants, and we speculate that delayed esophageal fluid clearance is
      the major underlying mechanism.

PMID- 19581817
TI  - Nonunion of the ulna after elastic stable intramedullary nailing for unstable
      forearm fractures: a case series.
AB  - Elastic stable intramedullary nailing (ESIN) for displaced forearm fractures in
      children has shown good results over the last two decades. To our knowledge,
      nonunion as complications after ESIN fixation of displaced forearm fractures is
      not well reported in English literature. In our institute, and over a period of
      10 years, we identified three cases of nonunion of the ulna after ESIN fixation
      of unstable and displaced forearm both bone fractures. Two patients had closed
      fractures and one patient had an open fracture. There was no deep infection in
      any case. All cases after revision surgery went into union.

PMID- 19581818
TI  - Intraobserver reliability of static measures in the normally developing infant
      foot and clubfoot.
AB  - Static measures data for infants are used in clinical practice and studies
      without published reliabilities. Intraobserver reliabilities for static measures
      were assessed in normally developing feet and clubfeet. Coefficient of
      repeatability was used for reliability. Variability in reliability was found.
      Ankle dorsiflexion, calf circumference and foot length were considered to be
      reliable in both groups. Foot width was considered unreliable and reliability for
      ankle plantarflexion knee flexed or extended does not seem to justify its use
      clinically. These results suggest that ankle dorsiflexion, calf circumference and
      foot length are reliable measures in infants and can be used for study
      conclusions and clinical decisions.

PMID- 19581819
TI  - Evaluation of the prognostic significance of serum galectin-3 in American Joint
      Committee on Cancer stage III and stage IV melanoma patients.
AB  - Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectins family and
      has been implicated in angiogenesis, tumor invasion, and metastatic process in
      vitro and in vivo. As we showed recently that advanced melanoma patients
      presented high serum level of Gal-3, we investigated the association of this
      protein with the outcome of melanoma patients. Whether this protein could be a
      biomarker has not been assessed, and we compared the prognostic value of serum
      Gal-3 in multivariate analysis with lactate dehydrogenase, C-reactive protein and
      S100B. We conclude that Gal-3 could be of prognostic value in melanoma patients;
      more precisely, this protein has a strong independent prognostic signification
      with a cut-off value of 10 ng/ml. After these data, we believe that serum Gal-3
      measurement can have an important role in the follow-up and management of
      advanced American Joint Commission on Cancer stage III and stage IV melanoma
      patients. Further studies will uncover whether Gal-3 will be able to open new
      therapeutic perspectives.

PMID- 19581821
TI  - An explorative study on quality of life and psychological and cognitive function
      in pediatric survivors of septic shock.
AB  - OBJECTIVE: To evaluate self-reported health-related quality of life, anxiety,
      depression, and cognitive function in pediatric septic shock survivors. DESIGN: A
      retrospective cohort study. SETTING: A 14-bed tertiary pediatric intensive care
      unit. PATIENTS: Children aged >or=8 yrs at the time of the follow-up who were
      admitted between 1995 and 2004 for septic shock. Inotropic and or
      vasoconstrictive agents were administered to these patients for >or=24 hrs.
      INTERVENTION: Health-related quality of life was assessed with the KIDSCREEN-52,
      anxiety with the State Trait Anxiety Inventory for Children, depression with the
      Children's Depression Inventory, and cognitive function with the cognitive scale
      of the TNO-AZL Children's Quality of Life Questionnaire Child Form. MEASUREMENTS
      AND MAIN RESULTS: Fifty of 82 eligible pediatric septic shock survivors were
      evaluated. The median age of the children at pediatric intensive care unit
      admission was 4.2 yrs (range, 0.0-17.0 yrs); the median age at follow-up was 10.7
      yrs (range, 8.0-20.4 yrs). Health-related quality of life and anxiety scores were
      comparable to the age-related Dutch norm population. Depression scores were
      significantly better than the norm population, whereas cognitive function was
      significantly lower than the norm population. We found that 44% of the children
      had cognitive scores <25% of the norm population. Young age at the time of
      pediatric intensive care unit admission was predictive of cognitive problems, and
      cognitive problems were associated with lower emotional function. CONCLUSIONS: In
      this group of septic shock survivors, health-related quality of life, anxiety,
      and depression are equal to or slightly better than the age-related Dutch norm
      population. Cognitive function is decreased, especially in children admitted at
      younger ages. Follow-up studies with adequate neuropsychological testing are
      warranted to evaluate the association between septic shock, cognitive function,
      and risk factors for cognitive problems.

PMID- 19581820
TI  - Pediatric cardiac arrest refractory to advanced life support: is there a role for
      terlipressin?
AB  - OBJECTIVE: Pediatric cardiac arrest unresponsive to advanced life support and
      several adrenaline doses has a very poor prognosis. Alternative vasopressors
      could improve the results of resuscitation in such cases. We report our
      experience with the compassionate administration of terlipressin in children who
      suffered in-pediatric intensive care unit cardiac arrest and did not respond to
      immediate advanced life support and at least three epinephrine doses. DESIGN:
      Prospective multicenter registry. SETTING: Three pediatric intensive care units
      at university-affiliated tertiary care children's hospitals. PATIENTS: Five
      pediatric patients, aged 5 mos to 12 yrs, with in-pediatric intensive care unit
      cardiac arrest unresponsive to advanced life support that included at least three
      epinephrine doses. INTERVENTIONS: Addition of terlipressin (10-20 microg/kg
      intravenous, up to two doses) to standard cardiopulmonary resuscitation.
      MEASUREMENTS AND MAIN RESULTS: Sustained return of spontaneous circulation was
      achieved in four cases, two of them were declared dead 6 and 12 hrs later, and
      the remaining two survived without cardiopulmonary procedures-related sequelae
      and with good neurologic condition. CONCLUSIONS: Terlipressin might contribute to
      obtain sustained return of spontaneous circulation in children with refractory in
      hospital cardiac arrest. A randomized controlled clinical trial should be
      conducted to investigate the optimal drug treatment in pediatric cardiac arrest.

PMID- 19581822
TI  - Pacemaker therapy of postoperative arrhythmias after pediatric cardiac surgery.
AB  - OBJECTIVE: To summarize the practical operation of temporary pacemakers in common
      use pertinent to the intensivist caring for the postcardiac patient. Pacemaker
      therapy is commonly required in the postoperative period after congenital cardiac
      surgery. DATA SYNTHESIS: Monitoring the hemodynamic status and availability of
      equipment for resuscitation is always important in any patient requiring a
      temporary pacemaker. Two important scenarios to consider in the pediatric
      intensive care unit are: 1) the patient in whom pacing has been initiated to
      optimize cardiac function; and 2) the patient without demonstrable spontaneous
      electrical activity or with extreme bradycardia. A number of different models of
      temporary pacemaker are available. Management of the child requiring cardiac
      pacing requires an understanding of the indications for pacing, a thorough
      knowledge of the available pacemaker, and an ability to troubleshoot problems.
      CONCLUSIONS: As the most common arrhythmias post congenital cardiac surgery
      involve either rate or conduction abnormalities, temporary pacemaker systems are
      a common form of electrical therapy in the postoperative period.

PMID- 19581823
TI  - Ontogeny of bradykinin B1 receptors in the mouse kidney.
AB  - Kinins are vasoactive peptides that stimulate two G-protein coupled bradykinin
      receptors (B1R and B2R). B2R-knockout mice are salt sensitive and develop renal
      dysgenesis and hypertension if salt stressed during embryogenesis. B1R-knockout
      mice, on the other hand, are protected from inflammation and fibrosis. This study
      examined the spatiotemporal expression of B1R during renal organogenesis. The
      segmental nephron identity of B1R immunoreactivity was determined by costaining
      with markers of the collecting duct (Dolichos biflorus), proximal tubule
      (Dolichos tetraglonus), and nephron progenitors (Pax2). At E14.5, the B1R was
      confined to few cells in the metanephric mesenchyme. Abundance of B1R increased
      progressively during development. On E17.5, B1R was enriched in differentiating
      proximal tubular cells and by postnatal day 1, B1R was clearly expressed on the
      luminal aspect of the proximal tubule. Quantitative real-time PCR revealed that
      the levels of B1R mRNA more than double during renal maturation. We conclude that
      1) B1R expression correlates closely with nephron maturation; 2) lack of B1R in
      nephron progenitors suggests that B1R is unlikely to play a role in early
      nephrogenesis; and 3) enrichment of B1R in maturing proximal tubule suggests a
      potential role for this receptor in terminal differentiation of the proximal
      nephron.

PMID- 19581824
TI  - Breast-feeding is associated with a reduced frequency of acute otitis media and
      high serum antibody levels against NTHi and outer membrane protein vaccine
      antigen candidate P6.
AB  - Nontypeable Haemophilus influenzae (NTHi) causes acute otitis media (AOM) in
      infants. Breast-feeding protects against AOM and/or nasopharyngeal (NP)
      colonization; however, the mechanism of protection is incompletely understood.
      Children with AOM and healthy children were studied according to feeding status:
      breastfed,breast/formula fed, or formula fed. Cumulative episodes of AOM, ELISA
      titers of serum IgG antibodies to whole-cell NTHi and vaccine candidate outer
      membrane protein P6, bactericidal titers of serum and NP colonization by NTHi
      were assessed. A lower incidence of AOM was found in breast- versus formula-fed
      children. Levels of specific serum IgG antibody to NTHi and P6 were highest in
      breast-fed, intermediate in breast/formula fed, and lowest in formula-fed
      infants. Serum IgG antibody to P6 correlated with bactericidal activity against
      NTHi. Among children with AOM, the prevalence of NTHi in the NP was lower in
      breast- versus nonbreast-fed infants. We conclude that breast-feeding shows an
      association with higher levels of antibodies to NTHi and P6, suggesting that
      breast-feeding modulates the serum immune response to NTHi and P6. Higher serum
      IgG might facilitate protection against AOM and NP colonization in breast-fed
      children.

PMID- 19581825
TI  - Fibroblast growth factor 10 plays a causative role in the tracheal cartilage
      defects in a mouse model of Apert syndrome.
AB  - Patients with Apert syndrome (AS) display a wide range of congenital
      malformations including tracheal stenosis, which is a disease characterized by a
      uniform cartilaginous sleeve in place of a normally ribbed cartilagenous trachea.
      We have studied the cellular and molecular basis of this phenotype in a mouse
      model of AS (Fgfr2c(+/Delta) mice), which shows ectopic expression of Fgfr2b in
      mesenchymal tissues. Here we report that tracheal stenosis is associated with
      increased proliferation of mesenchymal cells, where the expression of Fgf10 and
      its upstream regulators Tbx4 and Tbx5 are abnormally elevated. We show that Fgf10
      has a critical inductive role in tracheal stenosis, as genetic knockdown of Fgf10
      in Fgfr2c(+/Delta) mice rescues this phenotype. These novel findings demonstrate
      a regulatory role for Fgf10 in tracheal development and shed more light on the
      underlying cause of tracheal defects in AS.

PMID- 19581827
TI  - Retention of the immunological proteins of pasteurized human milk in relation to
      pasteurizer design and practice.
AB  - Pasteurizing donor human milk inactivates bacteria that may be of concern to the
      preterm infant. However, current practice for Holder Pasteurization (62.5 degrees
      C for 30 min) is detrimental to the bioactivity of human milk. An experimental
      pasteurizer was used to determine the maximum temperature at which 90% of
      secretory IgA, lysozyme, and lactoferrin were retained and whether this
      temperature was capable of inactivating five common bacterial contaminants. The
      retention of these proteins was also compared using a commercially available
      bottle immersion or holding chamber system. After pasteurization at 62.5 degrees
      C for 30 min, the retention across all three systems was 72.3 +/- 3.6%, 21.8 +/-
      3.3%, and 39.4 +/- 11.5% for sIgA, lactoferrin, and lysozyme, respectively (n =
      22). The retention of all three proteins was at least 90% when human milk was
      pasteurized at 57 degrees C for 30 min, and this temperature was also effective
      at removing 99.9% of all inoculated bacterial species. In addition, human milk
      that was pasteurized in the experimental system had a significantly higher
      proportion of lysozyme compared with samples pasteurized in the bottle immersion
      system. These findings suggest that optimizing pasteurization temperature and
      improving pasteurizer design enhances the quality of pasteurized donor human
      milk.

PMID- 19581826
TI  - Characterization and culture of fetal rhesus monkey renal cortical cells.
AB  - The renal glomerulus is composed of endothelial and mesangial cells with
      podocytes contributing to glomerular filtration. Podocyte damage is associated
      with renal disorders, thus there is interest in these cells for regenerative
      medicine. These studies investigated the use of extracellular matrix (ECM) to
      grow third trimester fetal monkey renal cortical cells and to assess mature
      podocytes in culture. Immunohistochemistry provided a profile of podocyte
      differentiation with metanephric mesenchyme and developing podocytes nestin
      positive and synaptopodin negative, whereas mature podocytes were positive for
      both markers. Primary cell cultures devoid of mature podocytes were established
      on plastic and renal ECM. A cell population (nestin+/synatopodin-) cultured on
      renal ECM showed greater proliferative potential compared with plastic with
      limited podocytes developing in culture over time. Further investigation of
      individual components of ECM (laminin, fibronectin, collagen I, or collagen IV)
      indicated that collagen I supported the greatest proliferation similar to renal
      ECM, whereas a greater number of mature podocytes (nestin+/synaptopodin+) were
      observed on fibronectin. These results suggest that (1) culture of fetal monkey
      podocytes can be accomplished, (2) renal ECM and collagen I can support renal
      cortical cells in vitro, which may recapitulate the developing kidney in vivo,
      and (3) fibronectin can support podocyte differentiation in vitro.

PMID- 19581828
TI  - Inflammation mediated down-regulation of hepatobiliary transporters contributes
      to intrahepatic cholestasis and liver damage in murine biliary atresia.
AB  - To investigate the hypothesis that during the development of biliary atresia,
      early changes in hepatobiliary transport are mainly related to the inflammatory
      process and lead to intrahepatic cholestasis and subsequent liver injury, livers
      from mice with rhesus rotavirus-induced biliary atresia were analyzed for mRNA
      expression of hepatobiliary transporters, nuclear receptors, and inflammatory
      cytokines. Seven days after inoculation, despite high bile acid concentrations in
      the liver, gene expression of canalicular and basolateral hepatobiliary
      transporters and their regulatory nuclear receptors was down-regulated with
      concomitant increase in gene expression of inflammatory cytokines and rise in
      serum unconjugated bilirubin. At 14 d, hepatobiliary transporters and nuclear
      receptors remained down-regulated although the inflammatory response subsided.
      The percentage of conjugated bilirubin started to increase as extrahepatic
      biliary obstruction occurred. At 18 d, expression of hepatobiliary transporters
      remained low, expression of nuclear receptors returned to normal, while
      expression of inflammatory cytokines decreased further. Moreover, histology
      demonstrated progressive inflammation, bile duct damage, ductular proliferation,
      and hepatocyte necrosis. In conclusion, intrahepatic cholestasis due to
      inflammation-related down-regulation of basolateral and canalicular hepatobiliary
      transporters is an early event in the development of biliary atresia.
      Intrahepatic cholestasis contributes to the development of jaundice and liver
      injury.

PMID- 19581829
TI  - Increased cellular proliferation and inflammatory cytokines in tonsils derived
      from children with obstructive sleep apnea.
AB  - Adenotonsillar hypertrophy is the major pathophysiological mechanism underlying
      obstructive sleep apnea (OSA) and recurrent tonsillitis (RI) in children. The
      increased expression of various mediators of the inflammatory response in tonsils
      of patients with OSA prompted our hypothesis that the enhanced local and systemic
      inflammation in children with OSA would promote tonsillar proliferation. Mixed
      cell cultures from tonsils recovered during adenotonsillectomy in children with
      OSA and RI were established, and proliferative rates were assessed. Cells were
      also cultured to determine the levels of proinflammatory cytokines and
      antioxidant protein levels and mRNA expression. Global cell proliferative rates
      from OSA tonsils were significantly higher than RI (p < 0.01), with CD3, CD4, and
      CD8 cell proliferation being higher in OSA (p < 0.05). Moreover, proinflammatory
      cytokines, such as TNF-alpha, IL-6, and IL-1alpha, were highly expressed in OSA
      derived tonsils. Furthermore, thioredoxin (TRX), an antioxidant protein, was also
      highly expressed in OSA tonsils at the mRNA and protein levels (p < 0.01). Thus,
      T cells are in a highly proliferative state in the tonsils of children with OSA
      and are associated with increased production of proinflammatory cytokines and
      TRX, when compared with children with RI.

PMID- 19581830
TI  - Lactic acidosis in a newborn with adrenal calcifications.
AB  - A patient is reported who presented in the newborn period with an unusual
      combination of congenital lactic acidosis and bilateral calcifications in the
      adrenal medulla, visible on standard abdominal x-ray and ultrasound examination.
      At birth, the proband was hypotonic and dystrophic. She developed respiratory
      insufficiency, cardiomegaly, and hepatomegaly and died at the age of 38 d.
      Examination of postmortem heart muscle revealed multiple areas of myocardial
      infarction with dystrophic calcifications. In the medulla of the adrenal glands,
      foci of necrosis and calcifications, and in the liver, multiple zones of necrosis
      and iron deposition were detected. Biochemical analysis in heart muscle revealed
      a decreased activity of complex IV of the oxidative phosphorylation (OXPHOS) and
      in liver a combined deficiency involving the complexes I, III, IV, and V. The
      findings were suggestive of a defect in biosynthesis of the mitochondrially
      encoded subunits of the OXPHOS complexes. Extensive analysis of the proband's
      mitochondrial DNA revealed neither pathogenic deletions and point mutations nor
      copy number alterations. Relative amounts of mitochondrial transcripts for the
      ribosomal mitochondrial 12S rRNA (12S) and mitochondrial 16S rRNA (16S) were
      significantly increased suggesting a compensatory mechanism involving the
      transcription machinery to low levels of translation. The underlying molecular
      defect has not been identified yet.

PMID- 19581832
TI  - Circulatory effects of inhaled iloprost in the newborn preterm lamb.
AB  - Inhaled NO (iNO) has an established role in the treatment of pulmonary
      hypertension (PH) in the newborn. However, costs and potential toxicity
      associated with iNO have generated interest in alternative inhaled selective
      pulmonary vasodilators such as iloprost. In a preterm lamb model of respiratory
      distress syndrome, we studied effects of increasing doses of iloprost followed by
      iNO on right ventricular pressure (RVP) and circulation including cerebral
      oxygenation. Fetal sheep were randomized to three doses (0.2-4 mg/kg) of iloprost
      (n = 9) or saline (n = 10), administered as 15-min inhalations with 15-min
      intervals after a 60-min postnatal stabilization. No differences were found in
      RVP, arterial PO2, or cardiac index according to treatment. The cerebral
      oxygenation, measured with near-infrared spectroscopy, deteriorated in control
      lambs, but not in iloprost lambs. Iloprost treatment followed by iNO resulted in
      a larger decrease (p = 0.007) in RVP than saline treatment followed by iNO. In
      conclusion, iloprost stabilized cerebral oxygenation and when followed by iNO had
      a larger effect on RVP than iNO alone. Although species differences may be
      relevant, these results suggest that iloprost should be studied in newborn
      infants for the treatment of PH.

PMID- 19581833
TI  - Changes in microcirculation as early markers for infection in preterm infants--an
      observational prospective study.
AB  - In adults with severe sepsis, the disturbances of the sublingual microcirculation
      can be quantified with orthogonal polarization spectral imaging. We investigated
      the cutaneous microcirculation of preterm infants with proven infection (PosInf)
      and with suspected but unproven infection (NegInf). In 25 infants, orthogonal
      polarization spectral images were obtained daily, videos of the images were
      blinded, and analyzed off-line. Functional small vessel density (FSVD) was
      prospectively calculated from day 3 to day 30 of life. There were 17 episodes of
      proven and nine episodes of suspected but unproven nosocomial late onset
      infection. Four infants remained healthy. The data were analyzed for the 5 d
      before the start of antibiotics (day -5 until day -1). FSVD varied widely, but in
      the PosInf-group, we found a 10% decline from day -5 to day -1 (p = 0.013). There
      was no significant change over time in the NegInf-group (p = 0.58). Thus, in
      infants with proven infection, FSVD decreases already 1 d before changes in
      laboratory parameters. However, these changes in FSVD during infection are not
      represented by absolute values, but must be identified by daily intraindividual
      observation.

PMID- 19581831
TI  - Mammillary body and fornix injury in congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) is accompanied by reduced
      ventilatory sensitivity to CO2 and O2, respiratory drive failure during sleep,
      impaired autonomic, fluid, and food absorption regulation, and affective and
      cognitive deficits, including memory deficiencies. The deficits likely derive
      from neural injury, reflected as structural damage and impaired functional brain
      responses to ventilatory and autonomic challenges. Brain structures playing
      essential memory roles, including the hippocampus and anterior thalamus, are
      damaged in CCHS. Other memory formation circuitry, the fornix and mammillary
      bodies, have not been evaluated. We collected two high-resolution T1-weighted
      image series from 14 CCHS and 31 control subjects, using a 3.0-Tesla magnetic
      resonance imaging scanner. Image series were averaged and reoriented to a
      standard template; areas containing the mammillary bodies and fornices were over
      sampled, and body volumes and fornix cross-sectional areas were calculated and
      compared between groups. Both left and right mammillary body volumes and fornix
      cross-sectional areas were significantly reduced in CCHS over control subjects,
      controlling for age, gender, and intracranial volume. Damage to these structures
      may contribute to memory deficiencies found in CCHS. Hypoxic processes, together
      with diminished neuroprotection from micronutrient deficiencies secondary to
      fluid and dietary absorption issues, may contribute to the injury.

PMID- 19581834
TI  - Circulatory recovery is as fast with air ventilation as with 100% oxygen after
      asphyxia-induced cardiac arrest in piglets.
AB  - We investigated return of spontaneous circulation and of cerebral oxygenation
      after asphyxia-induced cardiac arrest, using ventilation with air, throughout, or
      with 100% oxygen for a shorter or longer period. Arterial pressure, heart rate,
      regional cerebral oxygen saturation (CrSO2), and brain tissue oxygen tension
      (PbtO2) were measured in 1-d-old piglets that were hypoventilated with air and
      left in apnea until cardiac arrest. They were randomly assigned to be
      resuscitated with air (n = 13), or with oxygen for 3 (n = 12) or 30 min (n = 13)
      and then with air. Nine, 10, and 10 animals, respectively, needed closed chest
      cardiac massage. One, none, and one, respectively, died. Median (quartile range)
      times from start of ventilation until heart rate reached 150 bpm were 67 (60-76),
      88 (76-126), and 68 (56-81) s. They were not significantly different, nor were
      the arterial pressure responses, times until CrSO2 reached 30%, or times until
      PbtO2 had increased by 0.1 kPa from its nadir. Peak PbtO2 values during
      resuscitation were 4.2 (3.3-5.4), 12 (6.4-15), and 25 (15-36) kPa. Thus, pure
      oxygen did not accelerate the recovery of circulation or of cerebral oxygenation,
      while even a brief exposure caused cerebral hyperoxia.

PMID- 19581835
TI  - Placental IL-10 dysregulation and association with bronchopulmonary dysplasia
      risk.
AB  - Cytokine profiles in amniotic fluid, cord serum, and tracheal aspirate of
      premature infants suggest a shift toward a proinflammatory state. Cytokines also
      contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). We
      hypothesize that the initiating events for BPD are reflected in the placenta and
      propose that placental expression of cytokines provide a blueprint of events
      leading to BPD. This is a retrospective, case-controlled study of placental
      cytokines of premature infants with (n = 49) and without (n = 49) BPD, matched
      for gender, birth weight, and year of birth at Women and Infants Hospital between
      2003 and 2005. Cytokine expression, including IL-6 and IL-10, was determined by
      immunohistochemistry in membrane rolls, umbilical cords, and placentas. IL-6 was
      similarly expressed in all tissues of infants with and without BPD. In contrast,
      anti-inflammatory cytokine IL-10 was less prominent in the placenta of patients
      with BPD compared with those without BPD. IL-10 expression in the villous
      trophoblast layer was associated with a reduced odds ratio of developing BPD
      (adjusted OR 0.08, 95% CI 0.01-0.70, p = 0.02). These results suggest that a
      placental balance between inflammatory and anti-inflammatory cytokines is crucial
      to normal lung organogenesis. Importantly, IL-10 seems to be protective against
      the development of BPD.

PMID- 19581836
TI  - Amino terminal pro B-type natriuretic peptide levels are elevated in the cord
      blood of neonates with congenital heart defect.
AB  - This prospective study investigates whether amino terminal proB-type natriuretic
      peptide (NT-proBNP) levels are elevated in neonates with congenital heart defect
      (CHD). NT-proBNP levels in the umbilical cord blood of 60 neonates with
      prenatally diagnosed CHD, in the cord blood of 200 control subjects, and in the
      plasma of the respective mothers were analyzed using an automated enzyme
      immunoassay. NT-proBNP concentrations in the cord blood of the CHD group were
      significantly elevated compared with controls [median (range): 158 pg/mL (378
      3631 pg/mL) and 626 pg/mL (153-2518 pg/mL); p value <0.001]. The NT-proBNP
      concentrations of the newborns and their mothers did correlate neither in the CHD
      nor in the control group. In 54 patients with CHD, NT-proBNP levels were measured
      on the median 5th day of life. They showed a significant increase (median 1665
      pg/mL and 19222 pg/mL; p < 0.001). NT-proBNP levels in the cord blood of neonates
      with CHD are significantly elevated and show a marked increase in the first week
      of life. Furthermore, this study confirms previously published reference
      intervals of NT-proBNP in the cord blood of healthy neonates as well as the
      finding that there is no exchange of NT-proBNP across the placenta.

PMID- 19581838
TI  - Expression of vasoactive intestinal peptide and related receptors in
      overcirculation-induced pulmonary hypertension in piglets.
AB  - The pathobiology of pulmonary arterial hypertension (PAH) is not understood
      completely. Recent observations in patients with PAH and in knockout models have
      raised the idea that a defect in vasoactive intestinal peptide (VIP) may be
      involved in PAH physiopathology. Therefore, we investigated the expressions of
      VIP, the related pituitary adenylate cyclase-activating polypeptide (PACAP), and
      their receptors (VPAC1, VPAC2, and PAC1) in piglets with overcirculation-induced
      pulmonary hypertension as an early-stage PAH model. Seventeen piglets were
      randomized to an anastomosis between the innominate and the main pulmonary
      artery, or to a sham operation. After 3 mo, a hemodynamic evaluation was
      performed and the lung tissue was sampled for biologic and histologic studies.
      The shunting increased pulmonary vascular resistance (PVR) by 100% and arteriolar
      medial thickness by 85%. VIP and VPAC1 gene expressions were decreased and
      increased, respectively. VPAC1 gene expression was positively correlated to PVR.
      VPAC2 and PAC1 immunoreactivity was seen in pulmonary arterial smooth muscle. VIP
      and PACAP immunostaining was observed in nerve fibers surrounding the pulmonary
      arterial smooth muscle. In conclusion, overcirculation-induced pulmonary
      hypertension is accompanied by a down-regulation of VIP signaling, without change
      in PACAP expression. These results are consistent with the notion that abnormal
      VIP signaling takes part in PAH pathogenesis.

PMID- 19581839
TI  - The effects of closed endotracheal suction on ventilation during conventional and
      high-frequency oscillatory ventilation.
AB  - In newborn infants, closed endotracheal tube (ETT) suction may reduce associated
      adverse effects, but it is not clear whether ventilation is maintained during the
      procedure. We aimed to determine the effect of ETT size, catheter size, and
      suction pressure on ventilation parameters measured distal to the ETT. Suction
      was performed on a test lung, ventilated with conventional (CMV) and high
      frequency oscillatory ventilation (HFOV) using ETT sizes 2.5-4.0 mm, catheter
      sizes 5-8 French gauge (Fr), and suction pressures 80-200 mm Hg. Tracheal and
      circuit peak inspiratory pressure, positive end-expiratory pressure, and tracheal
      tidal volume (VT) were recorded for each suction episode. During both CMV and
      HFOV, tracheal pressures and VT were considerably reduced by suctioning; this
      reduction was dependent on the combination of ETT, catheter, and suction
      pressure. Loss of VT, inflation pressure (CMV), and pressure amplitude (HFOV)
      occurred primarily with insertion of the catheter, and loss of end-expiratory
      pressure (CMV) and mean tracheal pressure (HFOV) occurred with the application of
      suction. Circuit pressures were reduced to lesser degree. We conclude that airway
      pressures and VT are not maintained during closed endotracheal suction with
      either CMV or HFOV, and choice of equipment and settings will affect the degree
      of interruption to ventilation.

PMID- 19581840
TI  - Epileptogenesis is increased in rats with neonatal isolation and early-life
      seizure and ameliorated by MK-801: a long-term MRI and histological study.
AB  - Early-life stress has been shown to destabilize the homeostatic synaptic
      plasticity and compromise the developing brain to the later encountered insults.
      This study would determine the long-term epileptogenic effect of neonatal
      isolation (NI) on early-life seizure. There were five groups: normal rearing (NR)
      rats; NI rats; NR rats suffering from status epilepticus (SE) at P12 (NR-SE); NI
      SE rats; NI-SE-MK801 rats. All adult rats were video monitored to detect
      behavioral seizures, examined with brain magnetic resonance imaging, and assessed
      for hippocampal NeuN-immunoreactive (NeuN-IR) cells. Behavioral seizures were
      detected in one of six NR-SE rats, all the NI-SE rats (eight of eight), and none
      in the NR, NI, or NI-SE-MK801 rats. High hippocampal T2 signal were only found in
      three of five NR-SE rats, five of six NI-SE rats, and one of five NI-SE-MK801
      rats. There was a significant decrease in the number of hippocampal NeuN-IR cells
      in the NR-SE and NI-SE groups, compared with the NR group, and MK-801 treatment
      ameliorated the neuronal loss. Our results demonstrated that NI led to an
      increase in epileptogenesis in rat pups with early-life SE, and treatment with MK
      801 could ameliorate brain injuries, indicating a critical role of N-methyl-d
      aspartic acid receptor in the epileptogenic process.

PMID- 19581841
TI  - The effect of suction method, catheter size, and suction pressure on lung volume
      changes during endotracheal suction in piglets.
AB  - We aimed to identify the effect of suction pressure and catheter size on change
      in lung volume during open and closed endotracheal suction. Anesthetized piglets
      (n = 12) were intubated with a 4.0-mm endotracheal tube. Lung injury was induced
      with saline lavage. Three suction methods (open, closed in-line, and closed with
      a side-port adaptor) were performed in random order using 6, 7, and 8 French
      gauge (FG) catheters, at vacuum pressures of 80, 140, and 200 mm Hg. Lung volume
      change was measured with respiratory inductive plethysmography. Overall, open
      suction resulted in greater lung volume loss during and at 60-s postsuction than
      either closed method (p < 0.001). When open and closed methods were analyzed
      separately, volume change was independent of catheter size and suction pressure
      with open suction. With closed suction, volume loss increased with larger
      catheter sizes and higher suction pressures (p < 0.001). With an 8-FG catheter
      and suction pressure of 140 or 200 mm Hg, volume loss was equivalent with open
      and closed suction. Lung volume changes are influenced by catheter size and
      suction pressure, as well as suction method. With commonly used suction pressures
      and catheter sizes, closed suction has no advantage in preventing loss of volume
      in this animal model.

PMID- 19581842
TI  - Asymmetric dimethylarginine in the maternal and fetal circulation in
      preeclampsia.
AB  - Preeclampsia is a leading cause of intrauterine growth restriction and preterm
      birth. Endothelial dysfunction is the common final pathway leading to clinical
      signs of preeclampsia including hypertension and proteinuria. Asymmetric
      dimethylarginine (ADMA) is an endogenous inhibitor of NOS and induces endothelial
      dysfunction by reversibly inhibiting NO production from l-arginine. The purpose
      of this study was to investigate maternal and fetal concentrations of ADMA, l
      arginine, and symmetric dimethylarginine (SDMA). Women with preeclampsia (n = 47)
      and controls (n = 51) who gave birth by cesarean section were included in the
      study. We analyzed the maternal plasma and umbilical vein and artery plasma. We
      found that not only maternal concentrations of ADMA and SDMA but also l-arginine
      were significantly higher in women with preeclampsia than in controls. In fetal
      samples, only SDMA concentrations were higher in the preeclampsia group than in
      controls. The median ADMA concentration was three times higher in the fetal
      circulation than in the maternal circulation, but there was no difference between
      the preeclampsia group and the control group, and the veno-arterious gradient
      indicated that the placenta was the source of ADMA.

PMID- 19581844
TI  - Divergent oncogenic changes influence survival differences between colon and
      rectal adenocarcinomas.
AB  - PURPOSE: Colorectal cancers develop through various mechanisms such as
      chromosomal instability, DNA mismatch repair deficiency (microsatellite
      instability), and epigenetic DNA promoter methylation (CpG island methylator
      phenotype). This study evaluated the disparity in neoplastic changes between
      colon and rectal cancers. METHODS: A clinic-based colorectal frozen tumor bank at
      a single institution was queried for colon and rectal adenocarcinomas. Tumor DNA
      was extracted and analyzed for microsatellite instability, methylation, and
      mutations in the oncogenes KRAS and BRAF. Patient demographics, tumor
      characteristics, and clinical outcomes were compared. RESULTS: The 268 patients
      with colon cancer and 89 with rectal cancer were similar in gender, tumor size,
      stage, and differentiation. Colon cancers had a higher incidence of
      microsatellite instability (27 percent) and methylator phenotype (28 percent)
      compared with rectal cancers (7 percent, 3 percent, respectively; P < 0.001).
      Although KRAS mutation rate was similar, colon cancers had a higher incidence of
      BRAF mutations (16.7 percent vs. 0 percent; P < 0.001). Microsatellite stable
      tumors had an increased risk of disease recurrence compared with microsatellite
      unstable tumors (odds ratio, 3.86). Despite overall differences in outcome
      between colon and rectal cancers, no significant difference in survival existed
      when similar molecular phenotypes were compared across anatomic sites.
      CONCLUSIONS: Although colon cancers are molecularly heterogeneous, rectal cancers
      arise mostly via a single neoplastic pathway. Genetic and molecular differences
      influence prognosis more than anatomic location and suggest that oncogenic
      pathways contribute to survival differences between colon and rectal cancers.

PMID- 19581843
TI  - Maternal substrate utilization programs the development of the metabolic syndrome
      in male mice exposed to high fat in utero.
AB  - Studies were conducted to determine whether maternal substrate utilization during
      pregnancy affects fetal growth and predisposes offspring to metabolic disease.
      Female wild-type (WT) and glucose transporter 4 heterozygous mice (G4+/-, a model
      of altered peripheral substrate utilization) were fed high-fat diet (HFD, 35.5%
      fat) or control chow (C, 9.5% fat) for 2 wk before mating, throughout pregnancy
      and lactation (IU/L). WT HFD females exhibited increased serum nonesterified
      fatty acid and lactate levels and increased hepatic mRNA expression of peroxisome
      proliferator-activated receptor gamma coactivator-1-beta and SREBP-1c, consistent
      with increased lipogenesis. G4+/- HFD females exhibited enhanced lipid clearance,
      and exposure to HFD did not increase hepatic gene expression. HFD independent of
      maternal genotype decreased fetal growth and birth weight. WT offspring were
      weaned onto a low-fat diet (5.6% fat). Male offspring of WT mothers exposed to
      HFD exhibited "catch-up" growth accompanied by increased adiposity, impaired
      glucose tolerance, and insulin sensitivity. In contrast, male offspring of G4+/-
      HFD mothers did not exhibit any characteristics of metabolic syndrome. These data
      suggest that differences in maternal substrate utilization influence offspring
      metabolic phenotype.

PMID- 19581845
TI  - The National Bowel Cancer Project: social deprivation is an independent predictor
      of nonrestorative rectal cancer surgery.
AB  - PURPOSE: This study was designed to assess the impact of social deprivation on
      rates of abdominoperineal excision of the rectum in the United Kingdom. METHODS:
      Data were extracted from the Association of Coloproctology of Great Britain and
      Ireland Colorectal Cancer Database (2000-2005). Social deprivation was assessed
      by using the Index of Multiple Deprivation (2004) score. Logistic regression was
      performed to identify independent predictors of nonrestorative surgery. RESULTS:
      A total of 12,128 patients underwent anterior resection or abdominoperineal
      excision for Dukes A-C cancer in 101 centers; 2,625 patients (21.6 percent)
      underwent abdominoperineal excision (median, 20.8 (interquartile range, 16.5
      27.9) percent per unit). Abdominoperineal excision rates decreased from 24.3 to
      18.2 percent (P < 0.001) and varied between the least and most deprived groups
      from 18 to 26.4 percent, respectively (P < 0.001). Independent predictors of
      abdominoperineal excision were: year of surgery (odds ratio = 0.855 per year
      increase, P < 0.001), female vs. male gender (odds ratio = 0.82, P < 0.001), use
      of neoadjuvant radiotherapy (odds ratio = 2.4, P < 0.001), and social deprivation
      (most vs. least deprived: odds ratio = 1.638, P < 0.001). CONCLUSIONS:
      Abdominoperineal excision rates vary considerably between centers. Gender and
      deprivation status independently predict formation of a permanent stoma. These
      results have important implications for intercenter comparisons of surgical
      quality and may suggest inequalities in health care provision.

PMID- 19581846
TI  - Etiology of delays in the initiation of adjuvant chemotherapy and their impact on
      outcomes for Stage II and III rectal cancer.
AB  - PURPOSE: This study was designed to evaluate the role of access to care and
      postsurgical recovery on delays in adjuvant chemotherapy for rectal cancer.
      METHODS: Using data from the linked Surveillance, Epidemiology, and End Results
      Medicare database, we analyzed patients with Stage II or III rectal cancer who
      received adjuvant chemotherapy after curative rectal cancer surgery between 1991
      and 2002. Logistic and Cox regressions were performed to assess determinants of
      adjuvant chemotherapy delays and outcomes in two cohorts: patients with access to
      medical oncology care because of prior neoadjuvant chemotherapy (Group A) and
      patients without such access (Group B). Length of postoperative hospital stay
      served as the main proxy for postsurgical recovery. RESULTS: A total of 442 and
      5,617 patients were included in Groups A and B, respectively. The median interval
      between surgery and adjuvant chemotherapy was 46 days in Group A and 42 days in
      Group B. Although 17 percent and 11 percent of patients in Groups A and B,
      respectively, waited three or more months for adjuvant chemotherapy, median
      overall survival was worse in this subset than in those who waited less than 3
      months (54 vs. 76 months, P < 0.01). Postoperative hospital stay independently
      predicted for adjuvant chemotherapy delay in both groups. Disparities in delays
      were seen only in Group B, such that patients who were older or black had greater
      odds of an adjuvant chemotherapy delay (for both, P < 0.05). CONCLUSION: Advanced
      age and black race contribute to adjuvant chemotherapy delays and inferior
      outcomes, but postoperative recovery is the more important driver.

PMID- 19581848
TI  - Long-term results of intersphincteric resection for low rectal cancer.
AB  - PURPOSE: Intersphincteric resection has been performed as an alternative to
      abdominoperineal resection for low rectal cancer. The purpose of this study was
      to assess the long-term results after intersphincteric resection in terms of the
      morbidity, oncologic safety, and defecatory function. METHODS: Between 1994 and
      2006, 107 consecutive patients with low rectal cancer had curative
      intersphincteric resection, categorized as total, subtotal, or partial resection
      of the internal anal sphincter. RESULTS: There were no mortalities. Neorectal
      mucosal prolapse in patients with total intersphincteric resection and coloanal
      anastomotic stenosis in patients with subtotal or partial intersphincteric
      resection were observed as characteristic late complications. The five-year
      disease-free survival rates classified according to the TNM stage were 100
      percent for stage I, 83.5 percent for stage II, and 72.0 percent for stage III
      cases. The five-year cumulative local recurrence rate after intersphincteric
      resection was 2.5 percent. Defecatory function, which was evaluated by bowel
      movement in a 24-hour period, and continence after intersphincteric resection
      were objectively good. The results of the multivariate analysis revealed that age
      was the only factor associated with a risk of fecal incontinence. CONCLUSION:
      Provided strict selection criteria are used, intersphincteric resection may be
      the optimal sphincter-preserving surgery for low rectal cancer.

PMID- 19581849
TI  - Diverticular disease associated with inflammatory bowel disease-like colitis: a
      systematic review.
AB  - PURPOSE: Diverticular-associated colitis significantly overlaps clinically with
      primary inflammatory bowel disease. However, the clinical and the pathologic
      features of diverticular-associated colitis suggest that it is a distinct
      clinical entity. METHODS: We performed a systematic review by use of multiple
      health care databases and gray literature, following predefined inclusion and
      exclusion criteria to determine the clinical, endoscopic, and pathologic features
      of diverticular-associated colitis, and recurrence rates following medical and
      surgical treatment. RESULTS: Two hundred twenty-seven participants were selected
      from 18 eligible studies, including our own patients (n = 13). The average age of
      disease onset was 64 years. The typical symptoms included tenesmus, hematochezia,
      and diarrhea. One hundred sixty-three of the 227 patients in these studies were
      classified as having diverticular-associated colitis, of which 142 were managed
      medically. Twenty-eight patients eventually required an operation. One-quarter
      (37 of 163) of the patients had recurrence of symptoms with an average follow-up
      time of three years. CONCLUSIONS: Diverticular-associated colitis is a distinct
      entity that presents with segmental colitis and a variety of clinical,
      endoscopic, and pathologic features. Diverticular-associated colitis should be
      considered in the presence of recurrent symptoms after resection for
      diverticulitis.

PMID- 19581850
TI  - Effect of prednisolone on local and systemic response in laparoscopic vs. open
      colon surgery: a randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: This study was designed to assess whether preoperative, short-term,
      intravenously administered high doses of methylprednisolone (30 mg/kg 90 minutes
      before surgery) influence local and systemic biohumoral responses in patients
      undergoing laparoscopic or open resection of colon cancer. METHODS: Fifty-two
      patients who were candidates for curative colon resection were randomly assigned
      to laparoscopic or open surgery and, in a double-blind design, assigned to
      receive methylprednisolone (n = 26) or placebo (n = 26). Pulmonary function,
      postoperative pain, C-reactive protein, interleukins 6 and 8, and tumor necrosis
      factor alpha were analyzed, as was patient outcome. RESULTS: The steroid and
      placebo groups were well balanced for preoperative variables, as were the
      subgroups of patients who underwent laparoscopic (methylprednisolone, n = 13;
      placebo, n = 13) and open surgery (methylprednisolone, n = 13; placebo, n = 13).
      No adverse events related to steroid administration occurred. In the
      methylprednisolone groups, significant improvement in pulmonary performance (P =
      0.01), pain control (P = 0.001), and length of stay (P = 0.03) were observed
      independent of the surgical technique. No differences in morbidity or anastomotic
      leak rate were observed among groups. CONCLUSION: Preoperative administration of
      methylprednisolone in colon cancer patients may improve pulmonary performance and
      postoperative pain, and shorten length of stay regardless of the surgical
      technique used (laparoscopy, open colon resection).

PMID- 19581851
TI  - Ten-year outcome after anal sphincter repair for fecal incontinence.
AB  - PURPOSE: This study aimed to report at ten years on the results of the same
      cohort that had been studied at five years who had undergone an anal sphincter
      repair for fecal incontinence. METHODS: Patients studied at five years were
      contacted after ten years and asked to fill out the Fecal Incontinence Quality of
      Life Scale, the Fecal Incontinence Severity Index, and the Bristol Stool Form
      Scale. RESULTS: Thirty-one of 44 (71 percent) patients were contacted. Median
      follow-up time was 129 (range, 113 to 208) months. Median age at surgery was 44
      (range, 22 to 80) years. No patients were fully continent at 129 months. Fecal
      Incontinence Severity Index and Fecal Incontinence Quality of Life scores were
      correlated with the age at surgery. Older patients had lower Fecal Incontinence
      Quality of Life scores (P = 0.001), reflecting a lower quality of life, and a
      higher patient-rated Fecal Incontinence Severity Index score (P = 0.01) and a
      higher surgeon-rated Fecal Incontinence Severity Index score (P = 0.005),
      denoting more severe fecal incontinence. The Bristol Stool Form Scale, not
      utilized at 77 months, showed a correlation to patient-rated Fecal Incontinence
      Severity Index (P = 0.04) and surgeon-rated Fecal Incontinence Severity Index (P
      = 0.02). Fecal Incontinence Severity Index scores were significantly higher in
      women who had more than two vaginal births. CONCLUSION: Continence after
      overlapping sphincter repair deteriorates in the long term. Long-term outcome was
      worse for patients who were older at the time of surgery or those with two or
      more vaginal births. The Bristol Stool Form Scale score correlates with the
      severity of incontinence, and may be used to guide the management of the
      patient's symptoms.

PMID- 19581852
TI  - Long-term anorectal and sexual function after overlapping anterior anal sphincter
      repair: a case-match study.
AB  - PURPOSE: The purpose of this study was to assess the impact of overlapping anal
      sphincter repair for fecal incontinence on overall pelvic organ function.
      METHODS: This study was a case-match study of 25 women undergoing overlapping
      anal sphincter repair from 1996 through 2003. Functional outcome was assessed
      using validated scoring systems. For each case, two controls matched for age and
      parity were assessed. RESULTS: Twenty-one patients responded to the
      questionnaires; mean follow-up time was 105 (SD, 33.6) months. Analyzing the
      Wexner incontinence score, the group median improved from 15 (range, 4-20) before
      the procedure to 8 (range, 2-18; P < 0.001) at follow-up.Conversely,
      postoperatively there was no difference in symptoms of urinary incontinence
      between groups. The Female Sexual Function Index of case patients was
      significantly lower than that of control patients (cases, 16.2 [2.3-33.6];
      controls, 26.1 [3.3-36]; P = 0.004). The Short-Form-12 physical health score was
      similar for both groups (mean +/- standard deviation: cases, 46.1 +/- 10.8;
      controls, 48.6 +/- 11.4; P = 0.220), whereas the mental health score of patients
      was significantly lower than that of controls (cases, 39.8 +/- 10.5; controls,
      47.1 +/- 8.5; P = 0.0057). CONCLUSION: Anal sphincter repair for localized
      sphincter defects may achieve excellent/good long-term functional results in 67
      percent of patients, as judged by patients. Despite repair, continence remained
      significantly inferior in patients as compared with healthy control subjects. In
      addition, sexual function was significantly diminished in patients as compared
      with controls, but no correlation with the severity of fecal incontinence was
      found.

PMID- 19581853
TI  - Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a
      new treatment option for fecal incontinence.
AB  - PURPOSE: NASHA Dx gel has been used extensively for treatments in the field of
      urology. This study was performed to evaluate NASHA Dx gel as an injectable anal
      canal implant for the treatment of fecal incontinence. METHODS: Thirty-four
      patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were
      injected with 4 x 1 ml of NASHA Dx gel, just above the dentate line in the
      submucosal layer. The primary end point was change in the number of incontinence
      episodes and a treatment response was defined as a 50 percent reduction compared
      with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS:
      The median number of incontinence episodes during four weeks was 22 (range, 2 to
      77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it
      was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders
      at 6 months, compared with 19 (56 percent) at 12 months. No long-term side
      effects or serious adverse events were reported. CONCLUSIONS: Submucosal
      injection of NASHA Dx gel is an effective treatment for fecal incontinence. The
      effect is sustained for at least 12 months. The treatment is associated with low
      morbidity.

PMID- 19581854
TI  - Transanal endoscopic microsurgery is feasible for adenomas throughout the entire
      rectum: a prospective study.
AB  - INTRODUCTION: Transanal endoscopic microsurgery for rectal adenomas is safe and
      has low recurrence rates. However, the feasibility of the procedure for all
      rectal adenomas is unclear. This issue was investigated prospectively. METHODS:
      From 1996 to 2007, 353 consecutive rectal adenomas were evaluated according to a
      standard protocol. Transanal endoscopic microsurgery was intended in all rectal
      adenomas. RESULTS: The median diameter was 3 cm and median distance was 8 cm. The
      peritoneum was opened peroperatively without any adverse effects in 8.7 percent.
      The conversion rate was 9.6 percent, with an alternative local procedure
      performed in 4.2 percent and a transabdominal procedure performed in 5.4 percent.
      Conversion rate correlated with the distance of the tumor (P = 0.007) and the
      operating surgeon's level of experience (P = 0.004). The median operation time
      was 45 minutes. Operation time correlated with specimen area, experience, and
      operating surgeon (all P < 0.001). All rectal adenomas were excised in one piece.
      Complete margins were observed in 85 percent. Rectal adenomas with incomplete
      margins were larger (P < 0.001) and were located more proximally (P < 0.001).
      Morbidity was 7.8 percent and mortality 0.6 percent. The median hospital stay was
      four days. The median follow-up was 27 months. The recurrence rate at three years
      was 9.1 percent. The median time from operation to recurrence was 12 (range, 4
      54) months. Resection margin status was a predictor of recurrence, with 6.1
      percent recurrence in cases of complete margins and 25.2 percent in cases of
      incomplete margins (P < 0.001). CONCLUSIONS: For nearly all rectal adenomas,
      transanal endoscopic microsurgery is safe, feasible, and has excellent results.

PMID- 19581855
TI  - Combined histomorphologic and immunohistochemical phenotype to predict the
      presence of vascular invasion in colon cancer.
AB  - PURPOSE: Vascular invasion is an adverse prognostic factor in colorectal cancer
      and often is considered an indication for systemic adjuvant therapy. The aim of
      this study was to develop a predictive model of vascular invasion in a large
      cohort of colon cancers with use of tumor-related features and
      immunohistochemical analysis of protein markers. METHODS: A tissue microarray
      including 427 colon cancers was evaluated for 14 immunohistochemical protein
      markers. Complete data on pT, pN, tumor grade, tumor border configuration,
      vascular invasion, and tumor diameter were available. Classification and
      regression tree analysis was performed. RESULTS: The presence of vascular
      invasion independently predicted adverse outcome (P < 0.001; hazard ratio = 1.52
      (1.3 to 1.8)) and decreased survival from 49.0 to 19.0 months (P < 0.001) even in
      lymph node-positive patients. Tumor border configuration, Ki67, urokinase
      plasminogen activator receptor, and Raf-1 kinase inhibitor protein expression
      were predictive of vascular invasion. The cross-validated misclassification rate
      was 23.7 percent indicating a significant predictive accuracy of this model.
      CONCLUSIONS: Tumor border configuration, Ki67, urokinase plasminogen activator
      receptor, and Raf-1 kinase inhibitor protein immunohistochemistry are highly
      predictive of vascular invasion and may play a decisive role in individualizing
      adjuvant treatment.

PMID- 19581856
TI  - Morphology of the mesorectum in patients with primary rectal cancer.
AB  - PURPOSE: The size and contents of the pelvis differ between the genders, and this
      may affect mesorectal size and shape. The aim of this prospective pilot study was
      to examine radiologically the applied anatomy of the mesorectum. METHODS: Fifty
      eight patients (35 male, 23 female) with primary rectal cancer who had suitable
      high-resolution staging pelvic magnetic resonance images between November 2002
      and July 2004 were studied. Ten variables of mesorectal morphology were measured
      on axial images at the ischial spines. The associations between morphologic
      variables and gender and body mass index were examined. RESULTS: Compared with
      female patients, male patients had a larger area of overall mesorectal package
      (3,776 mm2 vs. 2,772 mm2, P = 0.001), larger area of mesorectal fat (2,562 mm2
      vs. 1,842 mm2, P = 0.001), and higher ratio of anteroposterior to transverse
      diameter of the mesorectal package (0.82 vs. 0.56, P < 0.001). The anterior
      mesorectal fat buffer was significantly thinner in females than in males (2.9 mm
      vs. 7.8 mm, P < 0.001). Mesorectal fat area was greater in males with a body mass
      index >25 than with a body mass index <25. CONCLUSIONS: Males have a larger
      overall mesorectal package compared with females, mainly caused by mesorectal
      fat. The anterior mesorectal fat is significantly thinner in females than in
      males. Such morphologic differences may affect resection margin status.

PMID- 19581857
TI  - Systematic evaluation and description of anal pathology in HIV-infected patients
      during the HAART era.
AB  - PURPOSE: This study aimed to determine the prevalence of macroscopic anal lesions
      and associated factors in HIV-infected outpatients during the era of highly
      active antiretroviral therapy. METHODS: A randomly selected sample of patients
      with HIV-infection receiving follow-up care in the infectious diseases department
      of Bichat University Hospital was invited to participate in a systematic
      screening program consisting of anal examination with anoscopy and a standardized
      questionnaire. RESULTS: Of 516 patients, 473 (92 percent) participated. Overall,
      208 patients (44 percent) had at least one anal macroscopic lesion: 108 patients
      (22.8 percent) had human papilloma (HPV)-related lesions (condyloma with or
      without dysplasia), 67 (14.2 percent) had hemorrhoidal disease, 50 (10.6 percent)
      had anal fissures, and 44 (9.3) percent had other anal lesions. Independent
      significantly associated factors for anal condyloma were history of anal
      condyloma (OR, 2.09) and median number of episodes of sexual intercourse per
      month (OR, 1.03) in men who have sex with men; history of genital condyloma (OR,
      26.74), and unprotected sexual intercourse (OR, 7.47) in heterosexual men; and
      CD4 cell count below 200/mm3 (OR, 6.02), receptive anal intercourse (OR, 6.37),
      and history of anal condyloma (OR, 16.69) in women. Neither sexual behavior nor
      characteristics related to HIV infection were associated with hemorrhoidal
      disease or anal fissure. CONCLUSIONS: Because patients with HIV infections have a
      high prevalence of unreported anal lesions that may be highly contagious, involve
      risk of anal neoplasia, or negatively affect quality of life, systematic anal
      screening should be conducted in the HIV-infected population.

PMID- 19581858
TI  - The role of carcinoembriogenic antigen in predicting response and survival to
      neoadjuvant chemoradiotherapy for distal rectal cancer.
AB  - PURPOSE: Carcinoembriogenic antigen (CEA) is the most frequently used tumor
      marker in rectal cancer. A decrease in carcinoembriogenic antigen after radical
      surgery is associated with survival in these patients. Neoadjuvant
      chemoradiotherapy may lead to significant primary tumor downstaging, including
      complete tumor regression in selected patients. Therefore, we hypothesized that a
      decrease in CEA after neoadjuvant chemoradiotherapy could reflect tumor response
      to chemoradiotherapy, affecting final disease stage and ultimately survival.
      METHODS: Patients with distal rectal cancer managed by neoadjuvant
      chemoradiotherapy and available pretreatment and postchemoradiotherapy levels of
      CEA were eligible for the study. Outcomes studied included final disease stage,
      relapse, and survival, and these were compared according to initial CEA level,
      post-chemoradiotherapy CEA level, and the reduction in CEA. RESULTS: Overall 170
      patients were included. Post-chemoradiotherapy CEA levels <5 ng/ml were
      associated with increased rates of complete clinical response and pathologic
      response. Additionally, postchemoradiotherapy CEA levels <5 ng/ml were associated
      with increased overall and disease-free survival (P = 0.01 and P = 0.03). There
      was no correlation between initial CEA level or reduction in CEA and complete
      response or survival. CONCLUSION: A postchemoradiotherapy CEA level <5 ng/ml is a
      favorable prognostic factor for rectal cancer and is associated with increased
      rates of earlier disease staging and complete tumor regression.
      Postchemoradiotherapy CEA levels may be useful in decision making for patients
      who may be candidates for alterative treatment strategies.

PMID- 19581859
TI  - Epidermal growth factor receptor expression discrepancies in metastatic
      colorectal cancer patients treated with cetuximab plus irinotecan-based
      chemotherapy refractory to irinotecan and oxaliplatin.
AB  - PURPOSE: This study was designed to evaluate the efficacy and safety of cetuximab
      plus irinotecan-based therapy in metastatic colorectal cancer refractory to
      irinotecan and oxaliplatin. In addition, discrepancies in the expression of
      epidermal growth factor receptor were examined by immunohistochemistry using two
      different antibodies. METHODS: The records of patients with metastatic colorectal
      cancer who were heavily pretreated with irinotecan and oxaliplatin and
      subsequently received cetuximab plus irinotecan-based therapy were reviewed.
      Differences in the expression of epidermal growth factor receptor detected by the
      PharmDx antibody and the clone H11 antibody in these patients were compared.
      RESULTS: Between February 2005 and August 2007, 52 patients were treated; median
      age was 53.5 years. The confirmed overall response rate was 30.8 percent, and the
      disease control rate was 67.3 percent. Median time to progression was 3.1 months,
      and median overall survival was 8.1 months. Of the 27 patients evaluable for
      epidermal growth factor receptor status, epidermal growth factor receptor
      expression was positive in 12 patients (44.4 percent) using the clone H11
      antibody test and in 26 patients (96.3 percent) with the PharmDx kit. CONCLUSION:
      Cetuximab plus irinotecan-based therapy showed promising antitumor activity even
      in patients with metastatic colorectal cancer refractory to irinotecan and
      oxaliplatin. In addition, discrepancies in the expression of the epidermal growth
      factor receptor detected by the clone H11 antibody and the PharmDx kit were
      observed.

PMID- 19581861
TI  - Metastasis to the pancreas from colorectal cancer: is there a place for
      pancreatic resection?
AB  - PURPOSE: Pancreatic metastases from colorectal cancer are very rare, and the
      possible benefit of surgical treatment is not clearly defined. This study was
      designed to evaluate the outcome of patients undergoing pancreatic resection for
      metastatic colorectal cancer to the pancreas. METHODS: Nine patients underwent
      pancreatic resection for metastatic colorectal cancer between January 1980 and
      December 2006. The primary cancers were colon (n = 7) and rectal carcinoma (n =
      2). The median interval between primary treatment and detection of pancreatic
      metastases was 32.5 months. In three cases pancreatic metastases were synchronous
      with the primary tumor. RESULTS: Five patients underwent pancreaticoduodenectomy,
      and four underwent distal pancreatectomy. A left lateral liver section and three
      colon resections were simultaneously performed in four patients. There was no
      postoperative mortality, and only two patients experienced complications.
      Survival averaged 19.8 (median, 17.0; range, 5-30) months: seven patients died of
      metastatic disease, one for unrelated disease after five months, and one is alive
      with liver metastases 30 months after surgery. CONCLUSION: Surgical resection can
      be performed safely in patients with isolated pancreatic metastases from
      colorectal cancer and in selected patients with associated extrapancreatic
      disease. Although long-term survival is rare, surgery should be included,
      whenever possible, in the multimodality approach to this disease.

PMID- 19581862
TI  - Chromoendoscopy, narrow-band imaging colonoscopy, and autofluorescence
      colonoscopy for detection of diminutive colorectal neoplasia in familial
      adenomatous polyposis.
AB  - PURPOSE: This study was designed to compare the diagnostic yield of white light
      colonoscopy, chromoendoscopy, narrow-band imaging, and autofluorescence imaging
      in the detection of diminutive lesions. METHODS: Thirteen patients with
      adenomatous polyposis were examined by total colonoscopy using an instrument that
      incorporated both narrow-band and autofluorescence imaging. Colonoscopic images
      were obtained using white light colonoscopy, autofluorescence imaging, narrow
      band imaging, and chromoendoscopy. All images were captured at equivalent angles
      and distances from the colorectal mucosa. RESULTS: Chromoendoscopy detected the
      greatest number of lesions at all sites within the large intestine, and it
      detected a significantly greater number than the other procedures on the left
      side of the large intestine. Narrow-band imaging depicted a greater number of
      lesions than did white light in the transverse colon, descending colon, and
      rectum. Autofluorescence imaging showed a greater number of lesions than did
      white light in the rectum. The total number of depicted lesions under
      chromoendoscopy (43.3 +/- 38.5) was significantly greater than the total number
      detected with white light (12.2 +/- 13.9, P = 0.005), autofluorescence imaging
      (21.4 +/- 27.5, P = 0.0006), and narrow-band imaging (20.1 +/- 21.5, P = 0.003).
      Narrow-band imaging detected a significantly higher total number of lesions than
      did white light (P = 0.04). CONCLUSION: Chromoendoscopy is superior to white
      light colonoscopy, autofluorescence imaging, and narrow-band imaging for
      detection of diminutive colorectal lesions in adenomatous polyposis.

PMID- 19581863
TI  - Platelet-derived growth factor (subtype BB) is elevated in patients with
      colorectal carcinoma.
AB  - PURPOSE: Platelet-derived growth factor-BB plays a role in the development of
      vascular and lymphatic vessels in tumors. In this study plasma levels of platelet
      derived growth factor-BB were assessed preoperatively in patients with adenomas
      and colorectal cancer to determine whether platelet-derived growth factor-BB is a
      useful marker or prognostic indicator. METHODS: Patients with adenomas and
      colorectal cancer undergoing resection were assessed. Clinical and pathologic
      data and preoperative blood samples were collected. Plasma platelet-derived
      growth factor-BB levels (median, 95 percent confidence interval for median) were
      determined and the Kruskal-Wallis test and Mann-Whitney U test were used for
      analysis. RESULTS: One hundred seventy-nine patients were studied (91 with
      colorectal cancer, 88 with adenomas). Preoperative colorectal cancer platelet
      derived growth factor-BB levels were higher (1,771.1 pg/ml; confidence intervals,
      1,429-2,065) than in the benign neoplasm group (1083 pg/ml; confidence intervals,
      933-1,192, P < 0.001). In patients with colorectal cancer, a direct relationship
      was noted between platelet-derived growth factor-BB levels and disease severity.
      Despite the increase in platelet-derived growth factor-BB noted with increasing
      stage, the differences between the Stages 1, 2, 3, and 4 groups were not
      significant. CONCLUSION: Platelet-derived growth factor-BB levels were greater in
      patients with colorectal cancer (vs. patients with adenoma) and rose with
      increasing disease severity. Unfortunately, however, the modest differences
      between categories do not permit accurate stage determination.

PMID- 19581864
TI  - Management of pilonidal sinus disease with oblique excision and bilateral gluteus
      maximus fascia advancing flap: result of 278 patients.
AB  - PURPOSE: Excision followed by natal cleft depth reduction should be performed,
      with no leftover midline scar tissue, to prevent recurrence of pilonidal sinus,
      which is the main problem in the treatment of this disease. We investigated the
      potential advantages of this advancing flap technique, which we developed.
      METHOD: An S-type incision together with a bilateral gluteus maximus fascia
      advancing flap was applied on 278 (89 percent) patients, who did not have
      extensive gluteal involvement, of the 312 patients who had pilonidal sinus
      disease, between January 1997 and January 2007. No drainage was performed on any
      patient. RESULTS: All patients were discharged within 24 hours. Total
      complication rate was 7.2 percent and recurrence rate was 0.7 percent. The mean
      time off from work was 12 +/- 2 days (range, 10 to 22). The mean follow-up period
      was 66 +/- 32 months (range, 12 to 120). CONCLUSION: We suggest that this
      surgical procedure may successfully be applied to a large majority of the
      patients. It does not lead to unnecessary excision of healthy tissue because of
      its significantly simpler nature compared with the full-layer flap technique and
      its S-type incision, it does not create a midline scar tissue, and it is able to
      flatten the gluteal sulcus.

PMID- 19581865
TI  - Proximal diversion at the time of ileal pouch-anal anastomosis for ulcerative
      colitis: current practices of North American colorectal surgeons.
AB  - PURPOSE: Pelvic sepsis is a serious complication after ileal pouch-anal
      anastomosis for ulcerative colitis that may lead to pouch failure or poor
      function. Although a temporary loop ileostomy may be created at the time of ileal
      pouch-anal anastomosis to prevent or minimize the consequences of an anastomotic
      leak, research has suggested that an ileostomy can be safely omitted in selected
      patients. The purpose of this study was to examine the use of proximal diversion
      by colorectal surgeons at the time of ileal pouch-anal anastomosis for ulcerative
      colitis. METHODS: A questionnaire was mailed to all practicing fellows of The
      American Society of Colon and Rectal Surgeons in North America. Surgeons were
      asked to describe their typical practice for a number of clinical scenarios.
      RESULTS: Questionnaires were mailed to 913 American Society of Colon and Rectal
      Surgeons fellows, and 63 percent responded. For a patient who has had a prior
      colectomy and is not taking steroids, 27 percent of surgeons would perform ileal
      pouch-anal anastomosis alone, and 73 percent would perform ileal pouch-anal
      anastomosis with a loop ileostomy. For a patient who has not had previous surgery
      and is taking prednisone 40 mg/day, 16 percent of surgeons would perform a
      subtotal colectomy with an end ileostomy, 82 percent would perform a total
      proctocolectomy and ileal pouch-anal anastomosis with a loop ileostomy, and 2
      percent would perform a total proctocolectomy and ileal pouch-anal anastomosis
      without an ileostomy. There was no relationship between practice setting, annual
      ileal pouch-anal anastomosis volume, or years in practice and surgeon response
      for either scenario. CONCLUSIONS: The majority of surgeons create a temporary
      loop ileostomy at the time of ileal pouch-anal anastomosis for ulcerative
      colitis.

PMID- 19581866
TI  - Multimedia articles. Small-bowel tumors with extensive mesenteric involvement can
      be resected with careful dissection of the mesenteric vessels with good outcomes.
AB  - We show the video of the dissection and resection of a locally advanced jejunal
      adenocarcinoma, with the involvement of multiple loops, to the base of the
      mesentery. Complete resection was made possible by careful dissection of the
      jejunal vessels and superior mesenteric artery at the root of the small-bowel
      mesentery (see Video, Supplemental Digital Content 1,
      http://links.lww.com/A1308). The long-term outcome for this patient is good.

PMID- 19581867
TI  - Incidence and etiology of pelvic floor dysfunction and mode of delivery: an
      overview.
AB  - Elective cesarean section at patient request is becoming common place. Women are
      requesting the intervention for preservation of the pelvic floor, but there is
      conflicting evidence to suggest that this mode of delivery has such benefits. The
      risks vs. benefits of both vaginal delivery and cesarean section need to be well
      understood before deciding on a surgical delivery. This review outlines the
      current available evidence of the risks and benefits associated with vaginal
      delivery and elective cesarean section and the incidence and mechanisms of injury
      that lead to pelvic floor dysfunction. As in most surgical conditions, a better
      understanding of causality of pelvic floor dysfunction may help treatment
      effectiveness.

PMID- 19581868
TI  - Long-term functional outcome and risk factors for recurrence after surgical
      treatment for low and high perianal fistulas of cryptoglandular origin.

PMID- 19581869
TI  - Spinal cord stimulation for constipated patients.

PMID- 19581873
TI  - Paediatric inflammatory bowel disease during a 44-year period in Copenhagen
      County: occurrence, course and prognosis--a population-based study from the
      Danish Crohn Colitis Database.
AB  - AIM: To describe the development in incidence, disease localization, activity,
      surgery and prognosis in two Danish paediatric population-based inflammatory
      bowel disease (IBD) cohorts comparing the time periods 1962-1987 (period I) and
      1998-2006 (period II). MATERIALS AND METHODS: Incident IBD patients below 15
      years of age were included. Disease localization was classified according to the
      Montreal classification for ulcerative colitis (UC) patients and into small
      bowel, large bowel and small and large bowel combined for Crohn's disease (CD)
      patients. Disease activity and surgery in the first 2 years after diagnosis were
      assessed. Standardized cancer incidence rates and standardized mortality rates
      were calculated. RESULTS: One hundred and nineteen IBD patients (77 UC and 42 CD)
      were included. Comparing periods II and I, the incidence rate ratios were 0.81
      [95% confidence interval (CI): 0.5-1.4] and 15.6 (95% CI: 7.5-32.7) in UC and CD,
      respectively. The number of UC patients with extensive disease (E3) increased
      from period I to II (46.7 vs. 94.1%, P<0.001). No colectomies were performed in
      UC patients in period II compared with nine in period I (P = 0.13) within the
      first 2 years after diagnosis. For patients diagnosed in period I, the
      standardized cancer incidence rate for UC was 37.9 (95% CI: 4.6-136.7) after a
      median follow-up period of 26 years. CONCLUSION: We found a significant 15-fold
      increase in the incidence of CD and a significant increase in the number of UC
      patients with extensive disease in period II compared with period I. After a
      median follow-up time of 26 years, a possible increased risk of colorectal cancer
      in UC patients was detected.

PMID- 19581874
TI  - A high-throughput method for zebrafish sperm cryopreservation and in vitro
      fertilization.
AB  - This is a method for zebrafish sperm cryopreservation that is an adaptation of
      the Harvey method (Harvey et al., 1982). We have introduced two changes to the
      original protocol that both streamline the procedure and increase sample
      uniformity. First, we normalize all sperm volumes using freezing media that does
      not contain the cryoprotectant. Second, cryopreserved sperm are stored in
      cryovials instead of capillary tubes. The rates of sperm freezing and thawing
      (delta degrees C/time) are probably the two most critical variables to control in
      this procedure. For this reason, do not substitute different tubes for those
      specified. Working in teams of 2 it is possible to freeze the sperm of 100 males
      per team in approximately 2 hrs. Sperm cryopreserved using this protocol has an
      average of 25% fertility (measured as the number of viable embryos generated in
      an in vitro fertilization divided by the total number of eggs fertilized) and
      this percent fertility is stable over many years.

PMID- 19581875
TI  - Quantification of the yeast transcriptome by single-molecule sequencing.
AB  - We present single-molecule sequencing digital gene expression (smsDGE), a high
      throughput, amplification-free method for accurate quantification of the full
      range of cellular polyadenylated RNA transcripts using a Helicos Genetic Analysis
      system. smsDGE involves a reverse-transcription and polyA-tailing sample
      preparation procedure followed by sequencing that generates a single read per
      transcript. We applied smsDGE to the transcriptome of Saccharomyces cerevisiae
      strain DBY746, using 6 of the available 50 channels in a single sequencing run,
      yielding on average 12 million aligned reads per channel. Using spiked-in RNA,
      accurate quantitative measurements were obtained over four orders of magnitude.
      High correlation was demonstrated across independent flow-cell channels,
      instrument runs and sample preparations. Transcript counting in smsDGE is highly
      efficient due to the representation of each transcript molecule by a single read.
      This efficiency, coupled with the high throughput enabled by the single-molecule
      sequencing platform, provides an alternative method for expression profiling.

PMID- 19581877
TI  - When less is more: the PI3K pathway as a determinant of tumor response to dietary
      restriction.

PMID- 19581876
TI  - Synergistic drug combinations tend to improve therapeutically relevant
      selectivity.
AB  - Drug combinations are a promising strategy to overcome the compensatory
      mechanisms and unwanted off-target effects that limit the utility of many
      potential drugs. However, enthusiasm for this approach is tempered by concerns
      that the therapeutic synergy of a combination will be accompanied by synergistic
      side effects. Using large scale simulations of bacterial metabolism and 94,110
      multi-dose experiments relevant to diverse diseases, we provide evidence that
      synergistic drug combinations are generally more specific to particular cellular
      contexts than are single agent activities. We highlight six combinations whose
      selective synergy depends on multitarget drug activity. For one anti-inflammatory
      example, we show how such selectivity is achieved through differential expression
      of the drugs' targets in cell types associated with therapeutic, but not toxic,
      effects and validate its therapeutic relevance in a rat model of asthma. The
      context specificity of synergistic combinations creates many opportunities for
      therapeutically relevant selectivity and enables improved control of complex
      biological systems.

PMID- 19581878
TI  - Fertility control: the role of magnesium transporters in pollen development.

PMID- 19581880
TI  - Of mice and men.
AB  - We need a systematic way to formulate and tackle problems in nanotoxicology, and
      to compare and combine the results from individual studies.

PMID- 19581879
TI  - A detailed characterization of the adult mouse model of glycogen storage disease
      Ia.
AB  - Glycogen storage disease type Ia (GSDIa) is caused by a genetic defect in the
      hepatic enzyme glucose-6-phosphatase (G6Pase-alpha), which manifests as life
      threatening hypoglycemia with related metabolic complications. A G6Pase-alpha
      knockout (KO) mouse model was generated to study potential therapies for
      correcting this disorder. Since then, gene therapy studies have produced
      promising results, showing long-term improvement in liver histology and glycogen
      metabolism. Under existing protocols, however, untreated KO pups seldom survived
      weaning. Here, we present a thorough characterization of the G6Pase-alpha KO
      mouse, as well as the husbandry protocol for rearing this strain to adulthood.
      These mice were raised with only palliative care, and characterized from birth
      through 6 months of age. Once KO mice have survived the very frail weaning
      period, their size, agility, serum lipids and glycemic control improve
      dramatically, reaching levels approaching their wild-type littermates. In
      addition, our data reveal that adult mice lacking G6Pase-alpha are able to mate
      and produce viable offspring. However, liver histology and glycogen accumulation
      do not improve with age. Overall, the reliable production of mature KO mice could
      provide a critical tool for advancing the GSDIa field, as the availability of a
      robust enzyme-deficient adult offers a new spectrum of treatment avenues that
      would not be tolerated by the frail pups. Most importantly, our detailed
      characterization of the adult KO mouse provides a crucial baseline for accurately
      gauging the efficacy of experimental therapies in this important model.

PMID- 19581882
TI  - Strictly nanotubes in Beijing.
AB  - A collaboration between China's leading university and one of the world's biggest
      industrial companies is bringing a range of nanotube-based materials and devices
      to the market.

PMID- 19581881
TI  - Plenty of gloom and doom at the bottom?
AB  - The relationship between humans and technology is often viewed as a debate
      between technophobes who oppose technology, irrespective of its benefits, and
      technophiles who think that all technology is good. Chris Toumey prefers the
      cyborg point of view.

PMID- 19581885
TI  - Nanobiotechnology: A fluid approach to simple circuits.

PMID- 19581886
TI  - Nanoelectromechanical systems: Mass spec goes nanomechanical.

PMID- 19581887
TI  - Ferroelectric memory: Slim fast.

PMID- 19581888
TI  - Correlated electron systems: Better than average.

PMID- 19581889
TI  - Nanomaterials: Sticky but not messy.

PMID- 19581890
TI  - Nanotoxicology: How do nanotubes suppress T cells?

PMID- 19581891
TI  - Evaluation of nanoparticle immunotoxicity.
AB  - The pharmaceutical industry is developing increasing numbers of drugs and
      diagnostics based on nanoparticles, and evaluating the immune response to these
      diverse formulations has become a challenge for scientists and regulatory
      agencies alike. An international panel of scientists and representatives from
      various agencies and companies reviewed the imitations of current tests at a
      workshop held at the National Cancer Institute in Frederick, Maryland. This
      article outlines practical strategies for identifying and controlling
      interferences in common evaluation methods and the implications for regulation.

PMID- 19581892
TI  - Nanoscale shape-memory alloys for ultrahigh mechanical damping.
AB  - Shape memory alloys undergo reversible transformations between two distinct
      phases in response to changes in temperature or applied stress. The creation and
      motion of the internal interfaces between these phases during such
      transformations dissipates energy, making these alloys effective mechanical
      damping materials. Although it has been shown that reversible phase
      transformations can occur in nanoscale volumes, it is not known whether these
      transformations have a sample size dependence. Here, we demonstrate that the two
      phases responsible for shape memory in Cu-Al-Ni alloys are more stable in
      nanoscale pillars than they are in the bulk. As a result, the pillars show a
      damping figure of merit that is substantially higher than any previously reported
      value for a bulk material, making them attractive for damping applications in
      nanoscale and microscale devices.

PMID- 19581893
TI  - New aspects of the metal-insulator transition in single-domain vanadium dioxide
      nanobeams.
AB  - Many strongly correlated electronic materials have a domain structure that
      greatly influences the bulk properties and obscures the fundamental properties of
      the homogeneous material. Nanoscale samples, on the other hand, can be smaller
      than the characteristic domain size, thus making it possible to explore these
      fundamental properties in detail. Here, we report new aspects of the metal
      insulator transition, studied in single-domain vanadium dioxide nanobeams. We
      have observed supercooling of the metallic phase by 50 degrees C, an activation
      energy in the insulating phase that is consistent with the optical gap, and a
      connection between the metal-insulator transition and the equilibrium carrier
      density in the insulating phase. Our devices also provide a nanomechanical method
      for determining the transition temperature, enable measurements on individual
      metal-insulator interphase walls to be made, and allow general investigations of
      phase transitions in quasi-one-dimensional geometries.

PMID- 19581894
TI  - Observation of the triplet exciton in EuS-coated single-walled nanotubes.
AB  - Photon absorption by carbon nanotubes creates bound electron-hole pairs called
      excitons, which can exist in spin-polarized triplet or spin-unpolarized singlet
      configurations. Triplet excitons are optically inactive owing to the weak spin
      orbit coupling in nanotubes. This prevents the optical injection of electron spin
      into nanotubes for spintronic applications and limits the efficiency of
      photocurrent generation. Here, we show that it is possible to optically excite
      the triplet exciton by using a ferromagnetic semiconductor as a spin filter to
      mix the singlet and triplet excitons. The triplet contribution to the
      photocurrent is detected, representing the first direct evidence of the triplet
      exciton in carbon nanotubes.

PMID- 19581895
TI  - Multifunctional nanoarchitectures from DNA-based ABC monomers.
AB  - The ability to attach different functional moieties to a molecular building block
      could lead to applications in nanoelectronics, nanophotonics, intelligent sensing
      and drug delivery. The building unit needs to be both multivalent and
      anisotropic, and although many anisotropic building blocks have been created,
      these have not been universally applicable. Recently, DNA has been used to
      generate various nanostructures or hybrid systems, and as a generic building
      block for various applications. Here, we report the creation of anisotropic,
      branched and crosslinkable building blocks (ABC monomers) from which
      multifunctional nanoarchitectures have been assembled. In particular, we
      demonstrate a target-driven polymerization process in which polymers are
      generated only in the presence of a specific DNA molecule, leading to highly
      sensitive pathogen detection. Using this monomer system, we have also designed a
      biocompatible nanovector that delivers both drugs and tracers simultaneously. Our
      approach provides a general yet versatile route towards the creation of a range
      of multifunctional nanoarchitectures.

PMID- 19581896
TI  - Droplet networks with incorporated protein diodes show collective properties.
AB  - Recently, we demonstrated that submicrolitre aqueous droplets submerged in an
      apolar liquid containing lipid can be tightly connected by means of lipid
      bilayers to form networks. Droplet interface bilayers have been used for rapid
      screening of membrane proteins and to form asymmetric bilayers with which to
      examine the fundamental properties of channels and pores. Networks, meanwhile,
      have been used to form microscale batteries and to detect light. Here, we develop
      an engineered protein pore with diode-like properties that can be incorporated
      into droplet interface bilayers in droplet networks to form devices with
      electrical properties including those of a current limiter, a half-wave rectifier
      and a full-wave rectifier. The droplet approach, which uses unsophisticated
      components (oil, lipid, salt water and a simple pore), can therefore be used to
      create multidroplet networks with collective properties that cannot be produced
      by droplet pairs.

PMID- 19581897
TI  - Transfer of gold nanoparticles from the water column to the estuarine food web.
AB  - Within the next five years the manufacture of large quantities of nanomaterials
      may lead to unintended contamination of terrestrial and aquatic ecosystems. The
      unique physical, chemical and electronic properties of nanomaterials allow new
      modes of interaction with environmental systems that can have unexpected impacts.
      Here, we show that gold nanorods can readily pass from the water column to the
      marine food web in three laboratory-constructed estuarine mesocosms containing
      sea water, sediment, sea grass, microbes, biofilms, snails, clams, shrimp and
      fish. A single dose of gold nanorods (65 nm length x 15 nm diameter) was added to
      each mesocosm and their distribution in the aqueous and sediment phases monitored
      over 12 days. Nanorods partitioned between biofilms, sediments, plants, animals
      and sea water with a recovery of 84.4%. Clams and biofilms accumulated the most
      nanoparticles on a per mass basis, suggesting that gold nanorods can readily pass
      from the water column to the marine food web.

PMID- 19581898
TI  - Towards single-molecule nanomechanical mass spectrometry.
AB  - Mass spectrometry provides rapid and quantitative identification of protein
      species with relatively low sample consumption. The trend towards biological
      analysis at increasingly smaller scales, ultimately down to the volume of an
      individual cell, continues, and mass spectrometry with a sensitivity of a few to
      single molecules will be necessary. Nanoelectromechanical systems provide
      unparalleled mass sensitivity, which is now sufficient for the detection of
      individual molecular species in real time. Here, we report the first
      demonstration of mass spectrometry based on single biological molecule detection
      with a nanoelectromechanical system. In our nanoelectromechanical-mass
      spectrometry system, nanoparticles and protein species are introduced by
      electrospray injection from the fluid phase in ambient conditions into vacuum,
      and are subsequently delivered to the nanoelectromechanical system detector by
      hexapole ion optics. Precipitous frequency shifts, proportional to the mass, are
      recorded in real time as analytes adsorb, one by one, onto a phase-locked,
      ultrahigh-frequency nanoelectromechanical resonator. These first
      nanoelectromechanical system-mass spectrometry spectra, obtained with modest mass
      sensitivity from only several hundred mass adsorption events, presage the future
      capabilities of this approach. We also outline the substantial improvements that
      are feasible in the near term, some of which are unique to nanoelectromechanical
      system based-mass spectrometry.

PMID- 19581899
TI  - Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune
      function in mice.
AB  - The potential health effects of inhaling carbon nanotubes are important because
      of possible exposures in occupational settings. Previously, we have shown mice
      that have inhaled multiwalled carbon nanotubes have suppressed systemic immune
      function. Here, we show the mechanisms for this immune suppression. Mice were
      exposed to 0, 0.3 or 1 mg m(-3) multiwalled carbon nanotubes for 6 h per day for
      14 consecutive days in whole-body inhalation chambers. Only those exposed to a
      dose of 1 mg m(-3) presented suppressed immune function; this involved activation
      of cyclooxygenase enzymes in the spleen in response to a signal from the lungs.
      Spleen cells from exposed animals partially recovered their immune function when
      treated with ibuprofen, a drug that blocks the formation of cyclooxygenase
      enzymes. Knockout mice without cyclooxygenase enzymes were not affected when
      exposed to multiwalled carbon nanotubes, further confirming the importance of
      this enzyme in suppression. Proteins from the lungs of exposed mice suppressed
      the immune function of spleen cells from normal mice, but not those from knockout
      mice. Our findings suggest that signals from the lung can activate signals in the
      spleen to suppress the immune function of exposed mice.

PMID- 19581900
TI  - Self-assembled cationic peptide nanoparticles as an efficient antimicrobial
      agent.
AB  - Antimicrobial cationic peptides are of interest because they can combat multi
      drug-resistant microbes. Most peptides form alpha-helices or beta-sheet-like
      structures that can insert into and subsequently disintegrate negatively charged
      bacterial cell surfaces. Here, we show that a novel class of core-shell
      nanoparticles formed by self-assembly of an amphiphilic peptide have strong
      antimicrobial properties against a range of bacteria, yeasts and fungi. The
      nanoparticles show a high therapeutic index against Staphylococcus aureus
      infection in mice and are more potent than their unassembled peptide
      counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show
      that the nanoparticles can cross the blood-brain barrier and suppress bacterial
      growth in infected brains. Taken together, these nanoparticles are promising
      antimicrobial agents that can be used to treat brain infections and other
      infectious diseases.

PMID- 19581901
TI  - The rehabilitation of hemianopic dyslexia.
AB  - Hemianopic dyslexia is a frequent and disabling functional impairment following
      brain injury. This form of dyslexia is an acquired reading disorder whereby
      patients with homonymous visual field defects have persistent and severe reading
      difficulties, despite having intact language functions. Hemianopic dyslexia has
      received little attention from researchers and clinicians, and this article is
      the first to review the rehabilitation of patients with the condition. In light
      of advances in our knowledge about the nature and causes of hemianopic dyslexia,
      I critically examine the available treatment methods for visual field disorders
      and evaluate their efficiency in alleviating hemianopic dyslexia. On the basis of
      the reviewed evidence, I suggest that compensatory therapies, which attempt to
      reorganize eye-movement control, are superior to restorative therapies, which aim
      at visual field restitution. For the rehabilitation of hemianopic dyslexia, I
      recommend a treatment protocol that involves the systematic and repetitive
      practice of specific eye movements for reading. Despite increasing evidence for
      the effectiveness of this treatment protocol, which has clinically relevant long
      term benefits, the underlying mechanism of the therapeutic effect is still
      unclear. Indeed, more research is required to further improve the efficiency of
      rehabilitation in patients with hemianopic dyslexia.

PMID- 19581902
TI  - B-cell-directed therapies for autoimmune disease.
AB  - Approval of the anti-CD20 antibody rituximab for the treatment of moderate-to
      severe rheumatoid arthritis in patients who fail to respond to anti-tumor
      necrosis-factor agents has raised interest in B-cell-directed therapy for this
      disease. A number of direct and indirect modalities with distinct mechanisms of
      action are being investigated, including anti-CD20 and anti-CD22 therapies, and
      new approaches for blocking members of the tumor necrosis factor cytokine family
      including B cell activating factor (BAFF) and a proliferation ligand (APRIL),
      which are at late stages of clinical development. Clinical experience is most
      extensive with rituximab, and suggests that targeting 'autoimmune' memory B cells
      is a feasible approach for treating autoimmune disease. Although anti-CD20
      therapy has only been approved for rheumatoid arthritis thus far, data suggest
      this approach could be valid for other autoimmune diseases, including systemic
      lupus erythematosus, Sjogren's syndrome, vasculitides, autoimmune cytopenias, and
      neurologic and dermatologic autoimmune diseases. Additional studies of direct and
      indirect B-cell-directed treatments are needed before we can draw conclusions as
      to the value of this approach in patients with various autoimmune diseases and
      whether more precisely defined techniques than these are required to target the
      complex humoral system effectively.

PMID- 19581903
TI  - Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis.
AB  - Osteoblasts and adipocytes differentiate from a common pluripotent precursor, the
      mesenchymal stem cell (MSC). Studies have identified numerous transcription
      factors, and multiple extracellular and intracellular signaling pathways that
      regulate the closely linked processes of adipogenesis and osteoblastogenesis.
      Interestingly, inducers of differentiation along one lineage often inhibit
      differentiation along the other; for example, the transcription factor peroxisome
      proliferator-activated receptor gamma (PPARgamma) is a prime inducer of
      adipogenesis that inhibits osteoblastogenesis. The latest research has shown that
      inducers of osteoblastogenesis (such as bone morphogenetic protein 2 and Wnt
      ligands) use different mechanisms to suppress the transactivation function of
      PPARgamma during osteoblastogenesis from MSCs. Signaling via the canonical Wnt
      beta-catenin pathway inhibits PPARgamma mRNA expression, whereas signaling via
      the noncanonical Wnt pathway results in activation of a histone methyltransferase
      SETDB1 that represses PPARgamma transactivation through histone H3K9 methylation
      of target genes. This article summarizes Wnt and PPARgamma signaling in MSCs and
      the crosstalk between these pathways, and speculates on future clinical
      application of this knowledge as the basis of novel approaches for regeneration
      therapy.

PMID- 19581904
TI  - Hepatitis B virus variants.
AB  - HBV replicates through reverse transcription of an RNA intermediate; the inherent
      lack of proofreading causes a high mutation frequency. Mutations in the precore
      and core promoter regions that abolish or reduce the production of hepatitis B e
      antigen occur most commonly. Patients with these HBV variants remain viremic and
      can develop progressive liver disease. Mutations in the core promoter region are
      associated with an increased risk of hepatocellular carcinoma. Exogenous
      selection pressure might favor certain mutations. Mutations in the HBV polymerase
      that confer resistance to nucleoside and nucleotide analog treatments are a major
      barrier to the success of therapy for hepatitis B. The development of antiviral
      drug resistance negates the initial treatment response and can lead to hepatitis
      flares and hepatic decompensation. Prompt addition of another drug to which the
      virus is not cross-resistant is required. Mutations in the HBV surface protein
      that facilitate escape from host immunity are responsible for the failure of
      immune prophylaxis in infants who received HBV vaccine and in liver transplant
      recipients who received hepatitis B immune globulin.

PMID- 19581905
TI  - Acute pancreatitis: risk of recurrence and late consequences of the disease.
AB  - Research into the clinical management of acute pancreatitis has primarily focused
      on the immediate complications of the disease, whereas its late consequences have
      received less attention. These late sequelae of acute pancreatitis refer to
      complications that arise after the convalescence period, which lasts for 3-6
      months after the initial episode. In patients who do not undergo necrosectomy
      that involves removal of the exocrine gland, pancreatic exocrine function usually
      improves rather than deteriorates during follow-up. By contrast, glucose
      intolerance is likely to worsen over time in all patients with acute
      pancreatitis. Despite the risk of late complications for patients with acute
      pancreatitis, their long-term quality of life is usually good. The number of
      pancreatitis episodes a patient has experienced is an important factor that
      determines the severity of late complications of acute pancreatitis. Risk factors
      for the recurrence of acute pancreatitis episodes have now been identified. This
      Review focuses on data from studies that investigated the risk factors for
      recurrent attacks of acute pancreatitis, and discusses the late consequences of
      this disease.

PMID- 19581906
TI  - Barrett esophagus: histology and pathology for the clinician.
AB  - The incidence of adenocarcinoma of the esophagus and gastroesophageal junction
      has increased dramatically over the past 30 years. The major precursor to this
      type of adenocarcinoma is Barrett esophagus, which is defined as the conversion
      of normal squamous epithelium into metaplastic columnar epithelium. Abundant
      evidence suggests that adenocarcinoma in the setting of Barrett esophagus
      develops via a progressive sequence of histological and molecular events.
      Consequently, patients with Barrett esophagus routinely undergo endoscopic
      surveillance for early detection of neoplasia. Histological evaluation of mucosal
      biopsy samples from the esophagus and gastroesophageal junction for
      identification of goblet cells and evaluation of the presence, grade and extent
      of dysplasia is the mainstay of risk assessment for these patients. This Review
      provides physicians with a summary of the pertinent, clinically relevant
      histological features of Barrett esophagus and its neoplastic complications. The
      histology of Barrett esophagus and the gastroesophageal junction is summarized,
      and an overview of information necessary to interpret pathology reports from
      patients either with or without endoscopic evidence of Barrett esophagus is
      provided to appropriately guide management of patients. Close interaction between
      the clinician and the pathologist is essential for proper interpretation of
      biopsy results and to provide optimal surveillance or treatment strategies.

PMID- 19581907
TI  - New insights into the role of podocytes in proteinuria.
AB  - Disturbances in many different molecular pathways and interactions can lead to
      the same clinical end points of proteinuria and end-stage renal disease.
      Proteinuria is often accompanied by a cytopathological change in the glomerulus
      that is referred to as effacement (retraction) of the podocyte foot processes.
      The molecular mechanisms that lead to proteinuria and podocyte effacement are
      poorly understood; therefore, targeted therapies are lacking. During the past 5
      years, however, a large body of data has emerged in this field. The discovery of
      podocyte gene defects that underlie some hereditary proteinuric syndromes has
      changed our understanding of the relative contributions of components of the
      glomerular filter. Furthermore, pathogenic pathways activated in podocytes during
      proteinuria have been identified. Together, these findings pinpoint the podocyte
      as the most obvious candidate for therapeutic intervention. In the near future,
      the use of large-scale expression profiling platforms, transgenic mouse lines,
      and other in vivo gene delivery methods will further expand our understanding of
      the pathology of the glomerular filtration barrier, and perhaps reveal novel
      target molecules for the therapy of proteinuric kidney diseases.

PMID- 19581908
TI  - Controversies in the treatment of idiopathic membranous nephropathy.
AB  - Optimum treatment of idiopathic membranous nephropathy is both controversial and
      challenging. The most extensively studied and frequently used immunosuppressive
      regimens for this disease comprise alkylating agents plus corticosteroids or
      ciclosporin. All of these treatment options have inherent problems: they are not
      effective in all patients, partial-rather than complete-remissions are common,
      adverse effects are worrisome, and relapses after treatment cessation remain
      problematic. Alternative immunosuppressive agents have been tested in an effort
      to overcome these unresolved issues. This paper reviews the available evidence
      regarding both established and new agents for the treatment of patients with
      idiopathic membranous nephropathy, with an emphasis on the results of the most
      recent clinical trials.

PMID- 19581909
TI  - Adverse effects of anticancer agents that target the VEGF pathway.
AB  - Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an
      important part of standard therapy in multiple cancer indications. With expanded
      clinical experience with this class of agents has come the increasing recognition
      of the diverse adverse effects related to disturbance of VEGF-dependent
      physiological functions and homeostasis in the cardiovascular and renal systems,
      as well as wound healing and tissue repair. Although most adverse effects of VEGF
      inhibitors are modest and manageable, some are associated with serious and life
      threatening consequences, particularly in high-risk patients and in certain
      clinical settings. This Review examines the toxicity profiles of anti-VEGF
      antibodies and small-molecule inhibitors. The potential mechanisms of the adverse
      effects, risk factors, and the implications for selection of patients and
      management are discussed.

PMID- 19581910
TI  - Systems pathology--taking molecular pathology into a new dimension.
AB  - The wealth of morphological, histological, and molecular data from human cancers
      available to pathologists means that pathology is poised to become a truly
      quantitative systems science. By measuring morphological parameters such as tumor
      stage and grade, and by measuring molecular biomarkers such as hormone receptor
      status, pathologists have sometimes accurately predicted what will happen to a
      patient's tumor. While 'omic' technologies have seemingly improved
      prognostication and prediction, some molecular 'signatures' are not useful in
      clinical practice because of the failure to independently validate these
      approaches. Many associations between gene 'signatures' and clinical response are
      correlative rather than mechanistic, and such associations are poor predictors of
      how cellular biochemical networks will behave in perturbed, diseased cells. Using
      systems biology, the dynamics of reactions in cells and the behavior between
      cells can be integrated into models of cancer. The challenge is how to integrate
      multiple data from the clinic into tractable models using mathematical models and
      systems biology, and how to make the resultant model sufficiently robust to be of
      practical use. We discuss the difficulties in using mathematics to model cancer,
      and review some approaches that may be used to allow systems biology to be
      successfully applied in the clinic.

PMID- 19581911
TI  - Blood mononuclear cell gene expression signature of postpartum depression.
AB  - In sorrow thou shalt bring forth children (Genesis 3:16) seems as relevant today,
      with one of seven mothers afflicted by a depressive episode, constituting the
      most common medical complication after delivery. Why mothers are variably
      affected by mood symptoms postpartum remains unclear, and the pathogenesis and
      early molecular indicators of this divergent outcome have not been described. We
      applied a case-control design comparing differential global gene expression
      profiles in blood mononuclear cells sampled shortly after delivery at the time of
      inception of postpartum depression (PD). Nine antidepressant naive mothers
      showing high depressive scores and developing a persisting major depressive
      episode with postpartum onset were compared with 10 mothers showing low
      depressive scores and no depressive symptoms on prospective follow-up. A
      distinctive gene expression signature was observed after delivery among mothers
      with an emergent PD, with a significant overabundance of transcripts showing a
      high-fold differential expression between groups, and correlating with depressive
      symptom severity among all mothers. Early expression signatures correctly
      classified the majority of PD patients and controls. Those developing persisting
      PD exhibit a relative downregulation of transcription after delivery, with
      differential immune activation, and decreased transcriptional engagement in cell
      proliferation, and DNA replication and repair processes. Our data provide initial
      evidence indicating that blood cells sampled shortly after delivery may harbor
      valuable prognostic information for identifying the onset of persisting PD. Some
      of the informative transcripts and pathways may be implicated in the differential
      vulnerability that underlies depression pathogenesis.

PMID- 19581912
TI  - Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet
      in rats and repress genes controlling lipogenesis and VLDL assembling in liver.
AB  - OBJECTIVE: To determine whether proanthocyanidins can protect against
      dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that
      underlie this hypolipidemic effect. DESIGN AND MEASUREMENTS: Female Wistar rats
      were fed on a HFD for 13 weeks. They were divided into two groups, one of which
      was treated with a grape seed proanthocyanidin extract (25 mg kg(-1) of body
      weight) for 10 days. Plasma and liver lipids were measured by colorimetric and
      gravimetric analysis. Liver, muscle and adipose tissue were used to study the
      expression of genes involved in the synthesis and oxidation of fatty acids and
      lipoprotein homeostasis by real-time RT-PCR. RESULTS: The administration of
      proanthocyanidins normalized plasma triglyceride and LDL-cholesterol (both
      parameters significantly increased with the HFD) but tended to decrease
      hypercholesterolemia and fatty liver. Gene expression analyses revealed that
      proanthocyanidins repressed both the expression of hepatic key regulators of
      lipogenesis and very low density lipoprotein (VLDL) assembling such as SREBP1,
      MTP and DGAT2, all of which were overexpressed by the HFD. CONCLUSION: These
      findings indicate that natural proanthocyanidins improve dyslipidemia associated
      with HFDs, mainly by repressing lipogenesis and VLDL assembly in the liver, and
      support the idea that they are powerful agents for preventing and treating lipid
      altered metabolic states.

PMID- 19581913
TI  - Identification of waist circumference cutoffs for abdominal obesity in the
      Chinese population: a 7.8-year follow-up study in the Shanghai urban area.
AB  - AIM: To identify the appropriate visceral adipose tissue (VAT) cutoff values for
      the diagnosis of abdominal obesity in predicting diabetes and the corresponding
      waist circumference in the Chinese population. METHODS: At baseline, 381
      volunteers aged 35-75 years were enrolled without diabetes from the Shanghai
      urban area. Anthropometry and VAT area determined by magnetic resonance imaging
      were measured. During the average 7.8 years of follow-up, glucose tolerance was
      monitored. Receiver operating characteristic (ROC) curve analysis was used to
      define the optimal cutoff points for abdominal obesity. RESULTS: At the end of
      the study, 290 participants were followed up, in which 63 participants developed
      diabetes. Using ROC curve analyses in participants with normal glucose
      regulation, the appropriate VAT cutoff was 90 cm(2) for both genders to predict
      diabetes development. In logistic regression models, the relative risks (95%
      confidence intervals) of VAT value over 90 cm(2) were 3.35 (1.10-10.18, P=0.033)
      in men and 4.57 (1.73-12.07, P=0.002) in women after adjusted for age, impaired
      glucose regulation, hypertension and dyslipidemia. The optimal waist
      circumference cutoffs were 88 cm for men and 82 cm for women to indicate VAT
      value over 90 cm(2) in ROC analyses. CONCLUSION: VAT cutoff of 90 cm(2) is useful
      for defining visceral obesity in Chinese individuals. The appropriate waist
      circumference cutoffs for abdominal obesity are 88 cm for men and 82 cm for women
      in the Chinese population.

PMID- 19581915
TI  - Occurrence of candiduria in a population of chronically catheterized patients
      with spinal cord injury.
AB  - STUDY DESIGN: Prospective data collection. OBJECTIVES: To evaluate occurrence and
      characteristics of candiduria in a population of individuals with spinal cord
      injury (SCI) or multiple sclerosis (MS) and chronic catheter usage. Candiduria,
      or presence of Candida species in the urine, is a common clinical problem. It is
      most frequently seen in patients with indwelling urinary catheters. Many patients
      have these catheters in place chronically. Previous studies have shown that
      despite therapy, most patients with candiduria will develop the infection again
      and that complications such as invasive candidiasis are rare. However, there are
      no studies that specifically examine the role of candiduria in patients with SCI
      and long-term catheter use. SETTING: Inpatients and outpatients in a US Veterans
      Affairs spinal cord injury center. METHODS: Urinalysis, culture, patient
      demographic and clinical characteristics through chart review. RESULTS: Of 100
      total patients, 52 had paraplegia, 45 tetraplegia and 3 MS. Overall, 17 (17%)
      patients had candiduria, which was observed in urine culture. Antibiotic use was
      associated with an increased risk of developing candiduria. Indwelling catheter
      (urethral or suprapubic) usage was also significantly associated with candiduria;
      only one person on intermittent catheterization developed candiduria, which was
      not associated with adverse clinical outcomes. CONCLUSIONS: Antibiotic usage and
      indwelling catheterization were associated with candiduria. No participant in our
      study population developed invasive candidiasis, and persistence of candiduria
      was not frequent.

PMID- 19581914
TI  - The effects of an anabolic agent on body composition and pulmonary function in
      tetraplegia: a pilot study.
AB  - STUDY DESIGN: Prospective repeated-measures longitudinal study. OBJECTIVES: To
      determine if an 8-week course of an oral anabolic steroid can positively effect
      body composition or pulmonary function in healthy individuals with chronic
      tetraplegia. SETTING: United States. METHODS: Oxandrolone (20 mg per day) was
      administered for 8 weeks to 10 men with motor complete tetraplegia. Dual X-ray
      absorptiometry scans, pulmonary function tests (PFTs), serum lipids and liver
      function tests (LFTs) were obtained at baseline, 4, 8, 12 and 20 weeks. To
      analyze change over time, a repeated measures General Linear Model and
      nonparametric tests were utilized. RESULTS: Following treatment, total lean body
      mass (LBM) increased 1.9% and LBM of the arms increased 5.4%. Total body fat
      decreased 1.5%, and increased 3.9% in the arms and, on average, combined measures
      of PFTs improved 2.2%. High-density lipoprotein cholesterol decreased 31.8%, low
      density lipoprotein cholesterol increased 41.2%, and LFTs increased 9.7-65.6%
      while on therapy but all trended to baseline at 20 weeks. CONCLUSION: Baseline
      body composition was characterized by a high proportion of fat and a body mass
      index that underestimated chronic disease risk. Treatment with oxandrolone was
      associated with modest improvements in PFTs and in arm and total body LBM.
      Unfavorable changes in serum lipids and LFTs indicate that reported benefits of
      using oxandrolone in this population must be carefully weighed against potential
      adverse effects.

PMID- 19581916
TI  - Dietary supplement use in the spinal cord injury population.
AB  - STUDY DESIGN: Longitudinal, non-experimental. OBJECTIVES: To determine the
      following: (1) prevalence of supplement use in a representative sample of the
      chronic spinal cord injury (SCI) population; (2) most frequently consumed
      supplements; and (3) characteristics of consistent supplement users. SETTING:
      Ontario, Canada. METHODS: A structured questionnaire was used to collect
      demographic information from 77 community-dwelling adults with chronic SCI (50.6%
      paraplegia, 81.8% male, 42.4 + or - 11.9 years, body mass index (BMI) 25.4 + or -
      5.1 kg m(-2)). A standardized form was used to record dietary intake, including
      supplements, in the previous 24 h, at three time points (baseline, 6 months and
      18 months). Logistic regression and multivariate logistic regression were used to
      determine which characteristic(s) was (were) associated with consistent
      supplement use. RESULTS: Seventy-one percent of the sample reported using
      supplements at least once, with 50.6% being classified as consistent supplement
      users (at least twice across the three time points). The top three supplements
      consumed were multivitamins (25%), calcium (20%) and vitamin D (16%). Supplement
      use status was not associated with gender, level of injury, age, education,
      physical activity, BMI, smoking or alcohol intake. CONCLUSIONS: Dietary
      supplement use was common in our sample of individuals with long-standing SCI,
      but no common characteristics distinguished users from non-users. We suggest that
      health practitioners be aware of the high dietary supplement use in this
      population so that they can probe for type, dose and frequency, as supplements
      may have an important influence on dietary assessment results.

PMID- 19581917
TI  - Low-back pain in HTLV-I-associated myelopathy/tropical spastic paraparesis:
      nociceptive or neuropathic?
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To describe characteristics of low
      back pain in human T-cell lymphotropic virus type I (HTLV-I)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) patients and to identify its
      neuropathic and/or non-neuropathic pain components. SETTING: A reference center
      for the care of patients with HAM/TSP in Rio de Janeiro, Brazil. METHODS: A total
      of 90 patients with HAM/TSP referred by tertiary care centers were consecutively
      assessed. The patients were submitted to a clinical protocol that included Visual
      Analogue Scale (VAS), Timed Up and Go Test, Bodily Pain Domain of the Short Form
      36 Health Status Questionnaire, Douleur Neuropathique 4 Questions (Neuropathic
      Pain 4 Questions) (DN4) and McGill Pain Questionnaire. RESULTS: The prevalence of
      low-back pain in the studied sample was 75.5%; pain interferes with physical
      functioning and worsens with movement and physical effort. It can be relieved by
      analgesics and rest. Average pain intensity was 51.2 mm on VAS and 1.72 on DN4.
      The most frequent words used to describe low-back pain were throbbing, burning,
      jumping and aching. Surprisingly, 32.4% patients pointed the lower extremities as
      the most painful and used different descriptors. The most common drugs used were
      analgesics, nonsteroidal anti-inflammatory drugs and tricyclic antidepressants.
      CONCLUSIONS: Low-back pain in HAM/TSP patients has mainly nociceptive
      characteristics. Conversely, descriptors for lower extremities pain suggest a
      neuropathic origin.

PMID- 19581918
TI  - Physical activity and subjective well-being among people with spinal cord injury:
      a meta-analysis.
AB  - STUDY DESIGN: Meta-analysis of cross-sectional, quasi-experimental and
      experimental studies. OBJECTIVE: To determine if there is an association between
      physical activity (PA) and subjective well-being (SWB) among people living with
      spinal cord injury (SCI). METHODS: Literature searches were conducted using
      multiple databases (Embase, CINAHL, Medline, PsychINFO and SPORTDiscus) to
      identify studies involving people with SCI that included a measure of PA and at
      least one measure of SWB (for example, symptoms of depression, life satisfaction,
      mood). Relevant data were extracted from the studies and subjected to meta
      analysis. RESULTS: A total of 21 studies were retrieved yielding 78 effect sizes
      and a total sample size of 2354. Overall, there were statistically significant,
      small- to medium-sized effects for the relationships between PA and SWB (broadly
      defined), PA and depressive symptoms, and PA and life satisfaction. Studies using
      experimental and quasi-experimental designs yielded larger effects for SWB
      (broadly defined) and life satisfaction, than studies using nonexperimental study
      designs. CONCLUSIONS: There is a small- to medium-sized positive relationship
      between PA and SWB among people with SCI that holds across a wide range of
      measures and operational definitions of these constructs.

PMID- 19581919
TI  - Steady-state dendritic cells continuously inactivate T cells that escape thymic
      negative selection.
AB  - Induction of peripheral tolerance by steady-state peripheral dendritic cells
      (DCs) presenting self antigen may be important in preventing autoimmune diseases
      mediated by self-reactive T cells that escape thymic deletion. However, the
      relative contribution of thymic and peripheral tolerance to the inactivation of
      self-specific repertoires is yet to be clearly defined. Here we tested the
      relative contribution of thymic and peripheral tolerance induction, using mice
      (11c.OVA) in which ovalbumin (OVA) expression is genetically targeted to DCs in
      conjunction with mice (Vbeta5 TCR transgenic), where a polyclonal repertoire of
      OVA-specific T cells of diverse affinity is present. The expression of OVA in
      thymic DC reduced the frequency of OVA(257-264)-specific mature CD8 single
      positive thymocytes although some functional OVA-specific CD8(+) T cells escaped
      negative selection and were detectable in the periphery. After adult thymectomy,
      OVA(257-264)-reactive T cells declined in the periphery indicating that the
      repertoire of OVA(257-264)-specific T cells that escaped negative selection and
      egressed to the periphery, were susceptible to inactivation by steady-state
      peripheral DC. Thus, in the face of inefficient negative selection, peripheral
      tolerance induction to cognate antigen by resting DC is a crucial requirement for
      the inactivation of a self-specific repertoire.

PMID- 19581920
TI  - Investigation of inter-individual variability of the one-carbon folate pathway: a
      bioinformatic and genetic review.
AB  - Genetic polymorphisms in the one-carbon folate pathway have been widely studied
      in association with a number of conditions. Most of the research has focused on
      the 677C>T polymorphism in the coding region of the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene. However, there are a total of
      25 genes in this pathway coding for enzymes, transporters and receptors, which
      can be investigated using 267 tagging single nucleotide polymorphisms (SNPs);
      using SNP database (dbSNP), 38 non-synonymous SNPs with a minor allele frequency
      of >5% are present in these genes. Most of these variants have not been
      investigated in relation to disease or drug response phenotypes. In addition,
      their functional consequences are largely unknown. Prediction of the functional
      effect using six publicly available programs (PolyPhen, SIFT BLink, PMut, SNPs3D,
      I-Mutant2.0 and LS-SNP) was limited to functionally well-characterized SNPs such
      as MTHFR c.677C>T and c.1298A>C ranking low. Epigenetic modifications may also be
      important with some of these genes. In summary, to date, investigation of the one
      carbon folate pathway genes has been limited. Future studies should aim for a
      more comprehensive assessment of this pathway, while further research is also
      required in determining the functional effects of these genetic variants.

PMID- 19581921
TI  - The relationship between the reproducibility of holmium laser enucleation of the
      prostate and prostate size over the learning curve.
AB  - The purpose of this study was to analyze the relationship between the
      reproducibility of holmium laser enucleation of the prostate (HoLEP) and prostate
      size over the learning curve. We compared the outcome among three institutions in
      three subgroups on the basis of the weight of tissue retrieved. There were no
      significant differences in operating time, efficiency of the procedure, decrease
      in hemoglobin level and postoperative urinary incontinence among three
      institutions, only in patients with prostates >or=20 g-<40 g retrieved. Our data
      indicate that HoLEP is more reproducible in patients with a moderate-sized
      prostate over the learning curve.

PMID- 19581922
TI  - Obese men have higher-grade and larger tumors: an analysis of the duke prostate
      center database.
AB  - Obesity is associated with increased risk of positive surgical margins and
      prostate specific antigen (PSA) recurrence among men undergoing radical
      prostatectomy. To what degree positive margins contribute to poorer outcome is
      unclear. Thus, we sought to examine the association between body mass index (BMI)
      and more objective measures of tumor aggressiveness, tumor grade and size. We
      carried out a retrospective analysis of 2302 patients treated with radical
      prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was
      calculated by multiplying prostate weight by percent of specimen involved with
      cancer. Associations between BMI and tumor volume and high-grade disease (Gleason
      >or=4+3) independent of pre-operative clinical characteristics of age, race, PSA,
      clinical stage, biopsy Gleason sum, and year of surgery were assessed using
      linear and logistic regression, respectively. Mean and median BMI among all
      subjects was 28.1 and 27.6 kg m(-2), respectively. Increased BMI was
      significantly associated with younger age (P<0.001), black race (P<0.001), more
      recent year of surgery (P<0.001), and positive surgical margins (P<0.001). After
      adjusting for multiple clinical pre-operative characteristics, higher BMI was
      associated with a greater percent of the prostate involved with cancer (P=0.003),
      increased tumor volume (P<0.001), and high-grade disease (P=0.007). Men with a
      BMI >or=35 kg m(2) had nearly 40% larger mean tumor volumes than normal weight
      men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics.
      In this study, obese men undergoing radical prostatectomy had higher-grade and
      larger tumors, providing further evidence that obese men undergoing radical
      prostatectomy have more aggressive prostate cancers.

PMID- 19581923
TI  - The role of caveolin-1 in prostate cancer: clinical implications.
AB  - Caveolin-1 (cav-1) is reportedly overexpressed in prostate cancer cells and is
      associated with disease progression. Specific oncogenic activities of cav-1
      associated with Akt activation also occur in prostate cancer. A membrane
      associated protein, cav-1, is nonetheless secreted by prostate cancer cells;
      results of recent studies showed that secreted cav-1 can stimulate cell survival
      and angiogenic activities, defining a role for cav-1 in the prostate cancer
      microenvironment. Serum cav-1 levels were also higher in prostate cancer patients
      than in control men without prostate cancer, and the preoperative serum cav-1
      concentration had prognostic potential in men undergoing radical prostatectomy.
      Secreted cav-1 is therefore a potential biomarker and therapeutic target for
      prostate cancer.

PMID- 19581924
TI  - P-21-activated protein kinase-1 functions as a linker between insulin and Wnt
      signaling pathways in the intestine.
AB  - Hyperinsulinemia and type II diabetes are associated with an increased risk of
      developing colorectal tumors. We found previously that in intestinal cells,
      insulin or insulin-like growth factor-1 stimulates c-Myc and cyclin D1 protein
      expression through both Akt-dependent and Akt-independent mechanisms. The effect
      of Akt is attributed to the stimulation of c-Myc translation by mammalian target
      of rapamycin. However, Akt-independent stimulation was, associated with an
      increase in beta-catenin (beta-cat) in the nucleus and an increased association
      between beta-cat and T-cell factor binding sites on the c-Myc promoter, detected
      by chromatin immunoprecipitation. In this study, we show that insulin stimulated
      the phosphorylation/activation of p-21-activated protein kinase-1 (PAK-1) in an
      Akt-independent manner in vitro and in an in vivo hyperinsulinemic mouse model.
      Significantly, shRNA (small hairpin RNA)-mediated PAK-1 knockdown attenuated both
      basal and insulin-stimulated c-Myc and cyclin D1 expression, associated with a
      marked reduction in extracellular signal-regulated kinase activation and beta-cat
      phosphorylation at Ser675. Furthermore, PAK-1 silencing led to a complete
      blockade of insulin-stimulated beta-cat binding to the c-Myc promoter and
      cellular growth. Finally, inhibition of MEK, a downstream target of PAK-1,
      blocked insulin-stimulated nuclear beta-cat accumulation and c-Myc expression.
      Our observations suggest that PAK-1 serves as an important linker between insulin
      and Wnt signaling pathways.

PMID- 19581925
TI  - Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed
      in papillary renal cell carcinoma and leads to attenuated hypoxic response.
AB  - The onconeuronal cerebellar degeneration-related antigen Cdr2 is associated with
      paraneoplastic syndromes. Neoplastic expression of Cdr2 in ovary and breast
      tumors triggers an autoimmune response that suppresses tumor growth by developing
      tumor immunity, but culminates in cerebellar degeneration when Cdr2-specific
      immune cells recognize neuronal Cdr2. We identified Cdr2 as a novel interactor of
      the hypoxia-inducible factor (HIF) prolyl-4-hydroxylase PHD1 and provide evidence
      that Cdr2 might represent a novel important tumor antigen in renal cancer. Strong
      Cdr2 protein expression was observed in 54.2% of papillary renal cell carcinoma
      (pRCC) compared with 7.8% of clear-cell RCC and no staining was observed in
      chromophobe RCC or oncocytoma. High Cdr2 protein levels correlated with
      attenuated HIF target gene expression in these solid tumors, and Cdr2
      overexpression in tumor cell lines reduced HIF-dependent transcriptional
      regulation. This effect was because of both attenuation of hypoxic protein
      accumulation and suppression of the transactivation activity of HIF-1alpha. pRCC
      is known for its tendency to avascularity, usually associated with a lower
      pathological stage and higher survival rates. We provide evidence that Cdr2
      protein strongly accumulates in pRCC, attenuates the HIF response to tumor
      hypoxia and may become of diagnostic importance as novel renal tumor marker.

PMID- 19581926
TI  - The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73.
AB  - The transcription factor p73, a member of the p53 family, mediates cell-cycle
      arrest and apoptosis in response to DNA damage-induced cellular stress, acting
      thus as a proapoptotic gene. Similar to p53, p73 activity is regulated by post
      translational modification, including phosphorylation, acetylation and
      ubiquitylation. In C. elegans, the F-box protein FSN-1 controls germline
      apoptosis by regulating CEP-1, the single ancestral p53 family member. Here we
      report that FBXO45, the human ortholog of FSN-1, binds specifically to p73
      triggering its proteasome-dependent degradation. Importantly, SCF(FBXO45)
      ubiquitylates p73 both in vivo and in vitro. Moreover, siRNA-mediated depletion
      of FBXO45 stabilizes p73 and concomitantly induces cell death in a p53
      independent manner. All together, these results show that the orphan F-box
      protein FBXO45 regulates the stability of p73, highlighting a conserved pathway
      evolved from nematode to human by which the p53 members are regulated by an SCF
      dependent mechanism.

PMID- 19581927
TI  - C/EBPalpha expression is partially regulated by C/EBPbeta in response to DNA
      damage and C/EBPalpha-deficient fibroblasts display an impaired G1 checkpoint.
AB  - We observed that CCAAT/enhancer-binding protein (C/EBP)alpha is highly inducible
      in primary fibroblasts by DNA-damaging agents that induce strand breaks, alkylate
      and crosslink DNA as well as those that produce bulky DNA lesions. Fibroblasts
      deficient in C/EBPalpha (C/EBPalpha(-/-)) display an impaired G1 checkpoint as
      evidenced by an inappropriate entry into the S-phase in response to DNA damage,
      and these cells also display an enhanced G1/S transition in response to mitogens.
      The induction of C/EBPalpha by DNA damage in fibroblasts does not require p53.
      Electrophoretic mobility shift assay (EMSA) analysis of nuclear extracts prepared
      from ultraviolet B (UVB)- and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated
      fibroblasts showed increased binding of C/EBPbeta to a C/EBP consensus sequence
      and chromatin immunoprecipitation (ChIP) analysis also showed increased C/EBPbeta
      binding to the C/EBPalpha promoter. To determine whether C/EBPbeta has a function
      in the regulation of C/EBPalpha, we treated C/EBPbeta(-/-) fibroblasts with UVB
      or MNNG. We observed that C/EBPalpha induction was impaired in both UVB- and MNNG
      treated C/EBPbeta(-/-) fibroblasts. Our study shows a novel function for
      C/EBPbeta in the regulation of C/EBPalpha in response to DNA damage and provides
      definitive genetic evidence that C/EBPalpha has a critical role in the DNA damage
      G1 checkpoint.

PMID- 19581928
TI  - Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human
      breast cancer cells.
AB  - Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated
      serum IL-6 correlates with poor breast cancer patient survival. Epithelial
      mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or
      aberrant Vimentin induction are associated with enhanced metastasis and
      unfavorable clinical outcome in breast cancer. Despite this fact, few tumor
      microenvironment-derived extracellular signaling factors capable of provoking
      such a phenotypic transition have been identified. In this study, we showed that
      IL-6 promoted E-cadherin repression among a panel of estrogen receptor-alpha
      positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing
      MCF-7 breast adenocarcinoma cells (MCF-7(IL-6)) exhibited an EMT phenotype
      characterized by impaired E-cadherin expression and induction of Vimentin, N
      cadherin, Snail and Twist. MCF-7(IL-6) cells formed xenograft tumors that
      displayed loss of E-cadherin, robust Vimentin induction, increased proliferative
      indices, advanced tumor grade and undifferentiated histology. Finally, we showed
      aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively
      express Twist, a metastatic regulator and direct transcriptional repressor of E
      cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer
      of an EMT phenotype in breast cancer cells and implicates its potential to
      promote breast cancer metastasis.

PMID- 19581929
TI  - Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill
      defined caspase.
AB  - Despite the early discovery of caspase-2, its physiological function has long
      remained an enigma. A number of recent publications now suggest not just one, but
      multiple functions, including roles in apoptosis, DNA repair and tumor
      suppression. How can one enzyme have so many talents? Considering the diversity
      of interaction partners and the specific mode of pro-apoptotic action proposed in
      these studies, caspase-2 might in fact represent a primordial protease serving
      numerous pathways, established before the advent of a more elaborate functionally
      diversified caspases system.

PMID- 19581930
TI  - Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and
      inhibiting erythroid differentiation.
AB  - Leukemogenesis requires two classes of mutations, one that promotes proliferation
      and one that blocks differentiation. The erythroleukemia induced by Friend virus
      is a multistage disease characterized by an early proliferative stage driven by
      the interaction of the viral glycoprotein, gp55, with Sf-Stk and the EpoR, and a
      late block to differentiation resulting from retroviral insertion in the Pu.1
      locus. We demonstrate here that activation of Stat3 by Sf-Stk in the early stage
      of disease is essential for the progression of erythroleukemia in the presence of
      differentiation signals induced by the EpoR, but is dispensable in the late
      stages of the disease. Furthermore, we identify Pu.1 as a Stat3 target gene in
      the early stages of erythroleukemia development. Our results support a model
      whereby the activation of Stat3 in the early stage of disease plays a pivotal
      role in regulating differentiation through the upregulation of Pu.1, thus
      inhibiting differentiation and favoring the expansion of infected erythroblasts
      and enhancing the pool of progenitors available for the acquisition of additional
      mutations, including insertional activation of Pu.1, resulting in full leukemic
      transformation.

PMID- 19581931
TI  - Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by preventing
      protein phosphatase 1 (PP1)-Axin interactions.
AB  - Wnt/beta-catenin signaling plays a pivotal role in modulating cellular
      proliferation, differentiation, tissue organization and embryonic development.
      Earlier, we found that the endocytic adaptor disabled-2 (Dab2) could attenuate
      Wnt/beta-catenin signaling by stabilizing Axin and preventing its translocation
      to the membrane. Recently, protein phosphatase 1 (PP1) has been shown to interact
      with, and dephosphorylate Axin, leading to its destabilization. Here, we show
      that Dab2 functions upstream of PP1 to block the interaction between Axin and
      PP1, inhibiting Axin dephosphorylation and thereby stabilizing its expression,
      ultimately leading to inhibition of Wnt/beta-catenin. We show that Dab2 acts as a
      competitive inhibitor of PP1 by binding to the same C-terminal domain of Axin.
      Both PP1 and Axin bind to the N-terminus of Dab2 and a Dab2 truncation mutant
      consisting of the N-terminal phosphotyrosine binding domain blocks PP1-Axin
      interactions and inhibits Wnt signaling. We confirm the inhibitory effect of Dab2
      on Wnt/beta-catenin signaling in zebrafish embryos, showing that its ectopic
      expression phenocopies Axin overexpression resulting in altered dorsoventral
      patterning. We conclude that Dab2 stabilizes Axin and attenuates Wnt/beta-catenin
      signaling by preventing PP1 from binding Axin.

PMID- 19581932
TI  - p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1.
AB  - Mainly regulated at the transcriptional level, the cellular cyclin-dependent
      kinase inhibitor, CDKN1A/p21(WAF1) (p21), is a major cell cycle regulator of the
      response to DNA damage, senescence and tumor suppression. Here, we report that
      COUP-TF-interacting protein 2 (CTIP2), recruited to the p21 gene promoter,
      silenced p21 gene transcription through interactions with histone deacetylases
      and methyltransferases. Importantly, treatment with the specific SUV39H1
      inhibitor, chaetocin, repressed histone H3 lysine 9 trimethylation at the p21
      gene promoter, stimulated p21 gene expression and induced cell cycle arrest. In
      addition, CTIP2 and SUV39H1 were recruited to the silenced p21 gene promoter to
      cooperatively inhibit p21 gene transcription. Induction of p21(WAF1) gene upon
      human immunodeficiency virus 1 (HIV-1) infection benefits viral expression in
      macrophages. Here, we report that CTIP2 further abolishes Vpr-mediated
      stimulation of p21, thereby indirectly contributing to HIV-1 latency. Altogether,
      our results suggest that CTIP2 is a constitutive p21 gene suppressor that
      cooperates with SUV39H1 and histone methylation to silence the p21 gene
      transcription.

PMID- 19581933
TI  - Emerging role of insulin-like growth factor receptor inhibitors in oncology:
      early clinical trial results and future directions.
AB  - Preclinical evidence that targeting the insulin-like growth factor receptor (IGF
      IR) is effective in cancer treatment has been accumulating for almost two
      decades. Efforts to develop drugs began in the late 1990s, and initial data from
      clinical trials were reported in 2006. The biological rationale for IGF-IR
      targeting has potential relevance to many tumor types, and early results have
      justified expanded programs to evaluate IGF-IR-targeting agents in many areas of
      clinical need. More than two dozen drug candidates have been developed and
      clinical trials are underway for at least 12 of these. Early clinical trials
      reveal an acceptable safety profile together with pharmacodynamic evidence that
      the receptor can be successfully targeted. It is premature to draw conclusions
      regarding efficacy, but well-documented instances of single-agent activity were
      noted during phase I evaluations, and recent evidence from a phase II study
      suggests that co-administration of an anti-IGF-IR antibody with chemotherapy for
      non-small-cell lung cancer improves objective response rate and progression-free
      survival. With more than 70 trials involving a variety of drug candidates
      underway, the IGF-IR is becoming one of the most intensively investigated
      molecular targets in oncology. Early results justify the continuation of ongoing
      research across a broad range of cancer indications.

PMID- 19581935
TI  - The tyrosine kinase Syk regulates the survival of chronic lymphocytic leukemia B
      cells through PKCdelta and proteasome-dependent regulation of Mcl-1 expression.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by accumulation of
      mature monoclonal CD5+ B cells. The disease results mainly from a failure of
      cells to undergo apoptosis, a process largely influenced by the existence of
      constitutively activated components of B-cell receptor signaling and the
      deregulated expression of anti-apoptotic molecules. Recent evidence pointing to a
      critical role of spleen tyrosine kinase (Syk) in ligand-independent BCR signaling
      prompted us to examine its role in primary B-CLL cell survival. We demonstrate
      that pharmacological inhibition of constitutive Syk activity and silencing by
      siRNA led to a dramatic decrease of cell viability in CLL samples (n=44),
      regardless of clinical and biological status and induced typical apoptotic cell
      death with mitochondrial failure followed by caspase 3-dependent cell death. We
      also provide functional and biochemical evidence that Syk regulated B-CLL cell
      survival through a novel pathway involving PKCdelta and a proteasome-dependent
      regulation of the anti-apoptotic protein Mcl-1. Together, our observations are
      consistent with a model wherein PKCdelta downstream of Syk stabilizes Mcl-1
      through inhibitory phosphorylation of GSK3 by Akt. We conclude that Syk
      constitutes a key regulator of B-CLL cell survival, emphasizing the clinical
      utility of Syk inhibition in hematopoietic malignancies.

PMID- 19581934
TI  - Impaired p53 binding to importin: a novel mechanism of cytoplasmic sequestration
      identified in oxaliplatin-resistant cells.
AB  - Previous studies have described one nuclear localization signal (NLSI) in p53 and
      speculated on two additional sites termed NLSII and NLSIII. Drug-resistant KB
      cells selected with cisplatin or oxaliplatin were found to have increased p53
      levels and in oxaliplatin-selected cells, a larger p53 predominantly in the
      cytoplasm. In oxaliplatin-selected cells a single nucleotide deletion in the
      sequence-encoding amino acid 382, part of NLSIII, resulted in a frame shift and a
      420 amino acid protein (p53(420)). We investigated explanations for the
      cytoplasmic sequestration of p53(420) while assessing the role, if any, of NLSII
      and NLSIII in p53 nuclear import. We found that neither NLSII nor NLSIII are
      essential for p53 nuclear localization. Furthermore, we confirmed p53(420) is
      able to tetramerize, transactivate a p21 promoter, bind dynein and that the
      reduced nuclear accumulation is not a consequence of increased p53 nuclear
      export. However, the association of p53(420) with importin-beta, essential for
      nuclear import, was significantly impaired. We conclude that despite sequence
      similarity to consensus NLSs neither NLSII nor NLSIII have roles in p53 nuclear
      transport. We also identified impaired association with importin as a novel
      mechanism of p53 cytoplasmic sequestration that impairs nuclear transport
      rendering cells functionally deficient in p53.

PMID- 19581937
TI  - A novel chloroplast-localized protein EMB1303 is required for chloroplast
      development in Arabidopsis.
AB  - To understand the molecular mechanisms underlying chloroplast development, we
      isolated and characterized the albino mutant emb1303-1 in Arabidopsis. The mutant
      displayed a severe dwarf phenotype with small albino rosette leaves and short
      roots on a synthetic medium containing sucrose. It is pigment-deficient and
      seedling lethal when grown in soil. Embryo development was delayed in the mutant,
      although seed germination was not significantly impaired. The plastids of emb1303
      1 were arrested in early developmental stages without the classical stack of
      thylakoid membrane. Genetic and molecular analyses uncovered that the EMB1303
      gene encodes a novel chloroplast-localized protein. Microarray and RT-PCR
      analyses revealed that a number of nuclear- and plastid-encoded genes involved in
      photosynthesis and chloroplast biogenesis were substantially downregulated in the
      mutant. Moreover, the accumulation of several major chloroplast proteins was
      severely compromised in emb1303-1. These results suggest that EMB1303 is
      essential for chloroplast development.

PMID- 19581936
TI  - Overexpression of Csk-binding protein contributes to renal cell carcinogenesis.
AB  - C-terminal Src kinase (Csk)-binding protein (Cbp) is a transmembrane adaptor
      protein that localizes exclusively in lipid rafts, where it regulates Src family
      kinase (SFK) activities through recruitment of Csk. Although SFKs are well known
      for their involvement in cancer, the function of Cbp in carcinogenesis remains
      largely unknown. In this study, we reported overexpression of Cbp in more than
      70% of renal cell carcinoma (RCC) specimens and in the majority of tested RCC
      cell lines. Depletion of Cbp in RCC cells by RNA interference led to remarkable
      inhibition of cell proliferation, migration, anchorage-independent growth as well
      as tumorigenicity in nude mice. Strikingly, silencing of Cbp negatively affected
      the sustaining of Erk1/2 activation but not c-Src activation induced by serum.
      Besides, the RhoA activity in RCC cells was remarkably impaired when Cbp was
      knocked down. Overexpression of wild-type Cbp, but not its mutant Cbp/DeltaCP
      lacking C-terminal PDZ-binding motif, significantly enhanced RhoA activation and
      cell migration of RCC cells. These results provided new insights into the
      function of Cbp in modulating RhoA activation, by which Cbp might contribute to
      renal cell carcinogenesis.

PMID- 19581938
TI  - An R2R3-type transcription factor gene AtMYB59 regulates root growth and cell
      cycle progression in Arabidopsis.
AB  - MYB proteins play important roles in eukaryotic organisms. In plants, the R1R2R3
      type MYB proteins function in cell cycle control. However, whether the R2R3-type
      MYB protein is also involved in the cell division process remains unknown. Here,
      we report that an R2R3-type transcription factor gene, AtMYB59, is involved in
      the regulation of cell cycle progression and root growth. The AtMYB59 protein is
      localized in the nuclei of onion epidermal cells and has transactivation
      activity. Expression of AtMYB59 in yeast cells suppresses cell proliferation, and
      the transformants have more nuclei and higher aneuploid DNA content with longer
      cells. Mutation in the conserved domain of AtMYB59 abolishes its effects on yeast
      cell growth. In synchronized Arabidopsis cell suspensions, the AtMYB59 gene is
      specifically expressed in the S phase during cell cycle progression. Expression
      and promoter-GUS analysis reveals that the AtMYB59 gene is abundantly expressed
      in roots. Transgenic plants overexpressing AtMYB59 have shorter roots compared
      with wild-type plants (Arabidopsis accession Col-0), and around half of the
      mitotic cells in root tips are at metaphase. Conversely, the null mutant myb59-1
      has longer roots and fewer mitotic cells at metaphase than Col, suggesting that
      AtMYB59 may inhibit root growth by extending the metaphase of mitotic cells.
      AtMYB59 regulates many downstream genes, including the CYCB1;1 gene, probably
      through binding to MYB-responsive elements. These results support a role for
      AtMYB59 in cell cycle regulation and plant root growth.

PMID- 19581941
TI  - Measurement of pump-induced transient lensing in a cryogenically-cooled high
      average power Ti:sapphire amplifier.
AB  - The transient thermal lensing in a liquid-nitrogren cooled kilohertz multipass
      amplifier is quantitatively measured with spatially-resolved Fourier transform
      spectral interferometry. A pump-probe arrangement allows the observation of a
      polarization-dependent non-thermal component following the fluorescence
      timescale: additional cooling would not suppress this residual lensing. We also
      observe a time-dependent thermal component that has a timescale sufficiently fast
      to indicate that there is cooling between shots even at a repetition rate of 1
      kHz. The value of pump-induced lensing would be underestimated when performing
      time-averaged measurements of pump-induced phase shifts.

PMID- 19581942
TI  - Planar wallpaper group metamaterials for novel terahertz applications.
AB  - We present novel metamaterial structures based upon various planar wallpaper
      groups, in both hexagonal and square unit cells. An investigation of
      metamaterials consisting of one, two, and three unique sub-lattices with resonant
      frequencies in the terahertz (THz) was performed. We describe the theory, perform
      simulations, and conduct experiments to characterize these multiple element
      metamaterials. A method for using these new structures as a means for
      bio/chemical hazard detection, as well as electromagnetic signature control is
      proposed.

PMID- 19581943
TI  - Nanoconcentration of terahertz radiation in plasmonic waveguides.
AB  - We establish the principal limits for the nanoconcentration of the THz radiation
      in metal/dielectric waveguides and determine their optimum shapes required for
      this nanoconcentration. We predict that the adiabatic compression of THz
      radiation from the initial spot size of R(0) approximately lambda(0) to the final
      size of R = 100- 250 nm can be achieved, while the THz radiation intensity is
      increased by a factor of x10 to x250. This THz energy nanoconcentration will not
      only improve the spatial resolution and increase the signal/noise ratio for the
      THz imaging and spectroscopy, but in combination with the recently developed
      sources of powerful THz pulses will allow the observation of nonlinear THz
      effects and a variety of nonlinear spectroscopies (such as two-dimensional
      spectroscopy), which are highly informative. This will find a wide spectrum of
      applications in science, engineering, biomedical research, environmental
      monitoring, and defense.

PMID- 19581944
TI  - Bend loss in highly multimode fibres.
AB  - We investigate the bend loss of highly multimode air-clad microstructured polymer
      optical fibre which displays low bend loss for small bend radii. After repeated
      bending the loss approached a plateau, decreasing significantly after a
      characteristic length. The loss at a particular point depended on the
      configuration of the fibre preceding that point. A simple analytical model based
      on a transfer-matrix method is derived to explain this behaviour in terms of the
      power distribution amongst different mode groups. This model allows the effect of
      a particular fibre configuration to be predicted.

PMID- 19581945
TI  - Surface plasmon resonance hydrogen sensor based on metallic grating with high
      sensitivity.
AB  - High sensitivity is obtained at larger resonant incident angle if negative
      diffraction order of metallic grating is used to excite the surface plasmon. A
      highly sensitive grating-based surface plasmon resonance (SPR) sensor is designed
      for the hydrogen detection. A thin palladium (Pd) film deposited on the grating
      surface is used as transducer. The influences of grating period and the thickness
      of Pd on the performance of sensor are investigated using rigorous coupled-wave
      analysis (RCWA) method. The sensitivity as well as the width of the SPR curves
      and reflective amplitude is considered simultaneously for designing the grating
      based SPR hydrogen sensor, and a set of optimized structural parameters is
      presented. The performance of grating-based SPR sensor is also compared with that
      of conventional prism-based SPR sensor.

PMID- 19581946
TI  - In vivo photoacoustic molecular imaging with simultaneous multiple selective
      targeting using antibody-conjugated gold nanorods.
AB  - The use of gold nanorods for photoacoustic molecular imaging with simultaneous
      multiple targeting is reported. Multiple targeting is done by utilizing the
      tunable optical absorption property of gold nanorods. This technique allows
      multiple molecular signatures to be obtained by simply switching laser
      wavelength. HER2 and EGFR were chosen as the primary target molecules for
      examining two cancer cells, OECM1 and Cal27. Both in vitro and in vivo mouse
      model imaging experiments were performed, with contrast enhancement of up to 10
      dB and 3.5 dB, respectively. The potential in improving cancer diagnosis is
      demonstrated.

PMID- 19581947
TI  - Experimental realization of broadband parametric generation in a quasi
      periodically poled LiTaO3.
AB  - We have achieved broadband parametric generation by using a quasi-periodically
      poled LiTaO(3) crystal as frequency converter. Tuning wavelength rang from 0.609
      microm to 5.208 microm, which covered three quasi-phase-matching processes, was
      obtained by means of changing the pump wavelength from 0.530 microm to 1.184
      microm. The experiment results are in good agreement with theory. The maximum
      conversion efficiency is 62% with a 10 Hz-5 ns pump source, at the average pump
      power of 0.5 mW. Our results exhibit a possible application of quasi-periodic
      superlattice in laser technology.

PMID- 19581948
TI  - The quantum-limited comb lineshape of a mode-locked laser: fundamental limits on
      frequency uncertainty.
AB  - We calculate the quantum-limited shape of the comb lines from a mode-locked
      Ti:sapphire laser using experimentally-derived parameters for the linear response
      of the laser to perturbations. The free-running width of the comb lines is found
      across the laser spectrum. By modeling the effect of a simple feedback loop, we
      calculate the spectrum of the residual phase noise in terms of the quantum noise
      and the feedback parameters. Finally, we calculate the frequency uncertainty in
      an optical frequency measurement if the limiting factor is quantum noise in the
      detection of the optical heterodyne beat.

PMID- 19581949
TI  - The effect of periodicity on the defect modes of large mode area microstructured
      fibers.
AB  - It is well known that periodic variations in refractive index can be used to
      create guidance in an optical fiber via photonic bandgap effects. It has also
      been shown that periodic structure in index-guiding microstructured fibers can
      lead to the guidance of additional leaky higher-order modes due to bandgap
      effects. Here we demonstrate that this additional guidance mechanism can have
      important practical implications in large mode area silica microstructured
      fibers. We also demonstrate that similar modes can exist when a bandgap is not
      present and attribute this guidance to a low density of states. Excellent
      agreement between theoretical predictions and experimental observations is
      demonstrated. We explore the impact of these additional modes on the practical
      operation of these fibers and explore ways of minimizing their effects via the
      fiber geometry.

PMID- 19581950
TI  - Growth parameter optimization for fast quantum dot SESAMs.
AB  - Semiconductor saturable absorber mirrors (SESAMs) using quantum dot (QD)
      absorbers exhibit a larger design freedom than standard quantum well absorbers.
      The additional parameter of the dot density in combination with the field
      enhancement allows for an independent control of saturation fluence and
      modulation depth. We present the first detailed study of the effect of QD growth
      parameters and post growth annealing on the macroscopic optical SESAM parameters,
      measuring both nonlinear reflectivity and recombination dynamics. We studied a
      set of self-assembled InAs QD-SESAMs optimized for an operation wavelength around
      960 nm with varying dot density and growth temperature. We confirm that the
      modulation depth is controlled by the dot density. We present design guidelines
      for QD-SESAMs with low saturation fluence and fast recovery, which are for
      example important for modelocking of vertical external cavity surface emitting
      lasers (VECSELs).

PMID- 19581951
TI  - On-demand ultrahigh-Q cavity formation and photon pinning via dynamic waveguide
      tuning.
AB  - We show that ultrahigh-Q wavelength-sized cavities can be reconfigurably formed
      by local refractive index tuning of photonic-crystal mode-gap waveguides. We have
      found that Q can be extraordinarily high (approximately 5 x 10(9)), which is much
      higher than that of structure-modulated mode-gap cavities. Furthermore, the
      required index modulation is extremely small (Deltan/n approximately 10(-3)),
      which enables dynamic cavity formation by fast optical nonlinearity. We
      numerically show that traveling photons in a waveguide can be pinned by fast
      local index tuning.

PMID- 19581952
TI  - Stable confinement of nanosecond laser pulse in an enhancement cavity.
AB  - We present a technique that enhances the intensity of a nanosecond laser pulse by
      confining it in an enhancement cavity. The point of the technique is that a weak
      continuous-wave laser radiation, locked to the enhancement cavity, is injected
      into a nanosecond injection-locked pulsed laser as a seed. This leads to a stable
      confinement of the nanosecond pulse in the enhancement cavity. It is demonstrated
      that the pulsed intensity is enhanced by a factor of 120 for a 40-ns pulse,
      consistent with the theoretical prediction.

PMID- 19581954
TI  - Sum-frequency generation of 589 nm light with near-unit efficiency.
AB  - We report on a laser source at 589 nm based on sum-frequency generation of two
      infrared laser at 1064 nm and 1319 nm. Output power as high as 800 mW is achieved
      starting from 370 mW at 1319 nm and 770 mW at 1064 nm, corresponding to
      converting roughly 90% of the 1319 nm photons entering the cavity. The power and
      frequency stability of this source are ideally suited for cooling and trapping of
      sodium atoms.

PMID- 19581953
TI  - Silicon optical fiber.
AB  - Described herein are initial experimental details and properties of a silicon
      core, silica glass-clad optical fiber fabricated using conventional optical fiber
      draw methods. Such semiconductor core fibers have potential to greatly influence
      the fields of nonlinear fiber optics, infrared and THz power delivery. More
      specifically, x-ray diffraction and Raman spectroscopy showed the core to be
      highly crystalline silicon. The measured propagation losses were 4.3 dB/m at
      2.936 microm, which likely are caused by either microcracks in the core arising
      from the large thermal expansion mismatch with the cladding or to SiO(2)
      precipitates formed from oxygen dissolved in the silicon melt. Suggestions for
      enhancing the performance of these semiconductor core fibers are provided. Here
      we show that lengths of an optical fiber containing a highly crystalline
      semiconducting core can be produced using scalable fiber fabrication techniques.

PMID- 19581955
TI  - Simulating the illuminance and the efficiency of the LED and fluorescent lights
      used in indoor lighting design.
AB  - In this study we simulate the illuminance and efficiency of four different types
      of reflector LED and fluorescent light sources for interior illumination.
      According to our calculation results of the examination of simulations and real
      situations, we find that the LEDs do perform better than fluorescent lights. We
      also consider the problems of glare with LED lights by utilizing a diffuser to
      protect the eyes. We are assured of the potential advantages of LED lighting in
      the future.

PMID- 19581956
TI  - Single-longitudinal mode Nd:YVO4 microchip laser with orthogonal-polarization
      bidirectional traveling-waves mode.
AB  - We present a single longitudinal mode, diode pumped Nd:YVO(4) microchip laser
      where a pair of quarter-wave plates (QWPs) sandwich Nd:YVO(4) and the principle
      axes of QWPs are oriented at 45 degrees to the c-axis of Nd:YVO(4). Three pieces
      of crystals were optically bonded together as a microchip without adhesive. Owing
      to large birefringence of Nd:YVO(4), two standing waves with orthogonal
      polarizations compensate their hole-burning effects with each other, which
      diminish total spatial hole-burning effects in Nd:YVO(4). The maximum pump power
      of greater than 25 times the threshold for single longitudinal mode operation has
      been theoretically shown and experimentally demonstrated. The power of output,
      slope efficiencies and temperature range of single longitudinal mode operation
      are greater than 730 mw (at 1.25 W pump), 60% and 30 degrees C, respectively.

PMID- 19581957
TI  - Localization of a fluorescent source without numerical fitting.
AB  - We present an algebraic solution to the problem of localizing a single
      fluorescent particle with sub-diffraction-limit accuracy. The algorithm is
      derived and its performance studied experimentally. Isolated 20 nm fluorescent
      beads were imaged using a wide-field microscope at two different positions
      separated by 100 nm and at a range of signal-to-noise ratios (SNR). The data were
      analyzed using both the new algorithm and the standard approach of fitting the
      data to a Gaussian profile. Results indicate that the proposed approach is nearly
      as accurate as Gaussian fitting across a wide range of SNR while executing over
      200 times faster. In addition, the new algorithm is able to localize at lower SNR
      than the fitting method.

PMID- 19581958
TI  - Experimental and numerical investigation of bit-wise phase-control OTDM
      transmission.
AB  - The impact of varying the phase relationship between adjacent OTDM channels is
      investigated in 80 Gbit/s transmission experimentally and numerically. A fiber
      based coherent multiplexer is proposed for OTDM experiments - a phase shifter in
      the multiplexer and an external phase control circuit are used to set and
      maintain the phase difference. It is demonstrated that the optimum modulation
      format for maximum transmission distance strongly depends on pulse width, e.g.
      120 degrees-RZ provides the best performance for pulse width of 8 ps; however, 90
      degrees-RZ is advantageous when pulse width is reduced to 2 ps. Power in 'zero'
      bit slots and amplitude jitter are calculated to demonstrate that the performance
      variation is due to intra-channel four-wave mixing (IFWM) and different receiver
      sensitivity at back-to-back. We also show that phase modulation formats are
      sensitive to optical filtering.

PMID- 19581959
TI  - Polarization splitter and polarization rotator designs based on transformation
      optics.
AB  - The transformation optics technique is employed in this paper to design two
      optical devices - a two-dimensional polarization splitter and a three-dimensional
      polarization rotator for propagating beams. The polarization splitter translates
      the TM- and the TE-polarized components of an incident beam in opposite
      directions (i.e., shifted up or shifted down). The polarization rotator rotates
      the polarization state of an incoming beam by an arbitrary angle. Both optical
      devices are reflectionless at the entry and exit interfaces. Design details and
      full-wave simulation results are provided.

PMID- 19581960
TI  - Femtosecond pulse generation around 1500 nm using a GaInNAsSb SESAM.
AB  - The operation of a femtosecond Cr(4+):YAG laser that incorporates a novel
      GaInNAsSb semiconductor saturable Bragg reflector is reported. In the mode-locked
      regime 230 fs pulses centred at 1528 nm were generated at an average output power
      of 280 mW. The SESAM exhibited a low saturation fluence of 10 microJ/cm(2) and a
      short recovery time of 12 ps.

PMID- 19581961
TI  - Surface plasmons in terahertz metamaterials.
AB  - We characterize terahertz metamaterials by applying apertureless near-field
      microscopy with a bandwidth that covers the entire spectral response of the
      structures. The observations agree with the interpretation of the fundamental
      mode of the metamaterial. But the high frequency resonance shows properties that
      deviate from the common interpretation. We show that the high frequency response
      is governed by surface Plasmon excitations, which have a comparable oscillator
      strength as the fundamental mode.

PMID- 19581962
TI  - Birefringent all-solid hybrid microstructured fiber.
AB  - We report the characterization of a birefringent all-solid hybrid microstructured
      fiber, in which the core-modes are guided by both the photonic bandgap (PBG)
      effect and total internal reflection (TIR). Due to the twofold symmetry, modal
      birefringence of 1.5 x 10(-4) and group birefringence of 2.1 x 10(-4) were
      measured at 1.31 microm, which is in the middle of the second bandgap. The band
      structure was calculated to be different from conventional 2-D PBG fibers due to
      the 1-D arrangement of high-index regions. The bend loss has a strong directional
      dependence due to the coexistence of the two guiding mechanisms. The fiber has
      two important properties pertinent to PBG fibers; spectral filtering, and
      chromatic dispersion specific to PBG fibers. The number of high-index regions,
      which trap pump power (by index guiding) when the fiber is used in cladding
      pumped fiber lasers, is greatly reduced so that this fiber should enable
      efficient cladding pumping. This structure is suitable for linearly-polarized,
      cladding-pumped fiber lasers utilizing the properties of PBG fibers.

PMID- 19581963
TI  - Focal modulation microscopy.
AB  - We report a novel light microscopy method for high resolution molecular imaging
      of thick biological tissues with one photon excited fluorescence. Effective
      optical sectioning and diffraction limited spatial resolution are achieved when
      imaging deep inside a multiple-scattering medium by the use of focal modulation,
      a technique for suppressing the background fluorescence signal excited by
      scattered light. Our method has been validated with animal tissue and an imaging
      depth around 600 microns has been demonstrated.

PMID- 19581964
TI  - Generation of Mathieu-Gauss modes with an axicon-based laser resonator.
AB  - We report what is to our best knowledge the first observation of Mathieu-Gauss
      modes directly generated in an axicon-based stable resonator. By slightly
      breaking the symmetry of the cavity we were able to generate single lowest and
      high-order Mathieu-Gauss modes of high quality. The observed transverse modes
      have an inherent elliptic structure and exhibit remarkable agreement with
      theoretical predictions.

PMID- 19581965
TI  - Performance comparison of delay-interferometer based direct detection oDOPSK
      receivers.
AB  - Performance evaluation of five different delay-interferometer based direct
      detection optical differential octal phase-shift keying receivers is reported.
      The performance is evaluated under an amplified spontaneous emission noise
      limited scenario using the well known Karhunen Loeve series expansion method. The
      classification of receivers into five different types is based on either the
      receiver schematic or the algorithm/methodology employed for symbol estimation.

PMID- 19581966
TI  - Preparative optical chromatography with external collection and analysis.
AB  - Optical chromatography, used for particle separation, involves loosely focusing a
      laser into a fluid flowing opposite the direction of laser propagation. When
      microscopic particles in the flow path encounter this beam they are trapped
      axially along the beam and are pushed upstream from the laser focal point to rest
      at a point where the optical and fluid forces on the particle balance. Because
      optical and fluid forces are sensitive to differences in the physical and
      chemical properties of a particle, separations are possible. An optical
      chromatography beam which completely fills a fluid channel can operate as an
      optically tunable filter for the preparative separation of polymeric/colloidal
      and biological samples. We show how the technique can be used to separate
      injected samples containing large numbers of colloids. The power of optical
      chromatographic separations is illustrated through combination with epi
      fluorescence microscopy and sample purification for real-time polymerase chain
      reaction (RT-PCR) detection of Bacillus anthracis spores.

PMID- 19581967
TI  - Gigahertz decoy quantum key distribution with 1 Mbit/s secure key rate.
AB  - We report the first gigahertz clocked decoy-protocol quantum key distribution
      (QKD). Record key rates have been achieved thanks to the use of self-differencing
      InGaAs avalanche photodiodes designed specifically for high speed single photon
      detection. The system is characterized with a secure key rate of 1.02 Mbit/s for
      a fiber distance of 20 km and 10.1 kbit/s for 100 km. As the present advance
      relies upon compact non-cryogenic detectors, it opens the door towards practical
      and low cost QKD systems to secure broadband communication in future.

PMID- 19581968
TI  - Nonreciprocal XeCl laser-induced aggregation of beta-crystallins in water
      solution.
AB  - The aggregation of a beta-crystallin water solution exposed to XeCl laser
      radiation demonstrates the dependence of scattering-exposure curve (scattering
      versus exposure) on laser intensity. The main features of this dependence can be
      understood by the relaxation of a partly denaturated state of a protein within
      some finite relaxation time. These photoactivated states originate from the
      absorption of UV photons. Two partly denaturated (photoactivated) monomers, as
      well as other aggregates, can aggregate, giving rise to sharply increasing probe
      light scattering after some lag time of irradiation.

PMID- 19581969
TI  - Experimental study of Brillouin scattering in fluorine-doped single-mode optical
      fibers.
AB  - We experimentally investigate Brillouin scattering properties in fluorine-doped
      single-mode optical fibers. The effective acoustic velocities determined from the
      measured dependences of acoustic resonance frequencies on optical wavelength are
      approximately equal to the individual acoustic velocities in the core and/or
      cladding regions. Brillouin gain coefficients are experimentally characterized
      and compared with that in a standard GeO(2)-doped single-mode fiber. The result
      indicates that the acousto-optic coupling efficiencies in all fibers are almost
      100%, which means that Brillouin threshold value can not be simply increased by
      fluorine doping. Moreover, it is found that the dependences of acoustic resonance
      frequencies on applied strain or temperature change are quantitatively enhanced
      by fluorine dopants, which is in opposite trend when compared with germanium
      ones.

PMID- 19581970
TI  - Optical gap formation and localization properties of optical modes in
      deterministic aperiodic photonic structures.
AB  - We theoretically investigate the spectral and localization properties of two
      dimensional (2D) deterministic aperiodic (DA) arrays of photonic nanopillars
      characterized by singular continuous (Thue-Morse sequence) and absolutely
      continuous (Rudin-Shapiro sequence) Fourier spectra. A rigorous and efficient
      numerical technique based on the 2D Generalized Multiparticle Mie Theory is used
      to study the formation of optical gaps and the confinement properties of
      eigenmodes supported by DA photonic lattices. In particular, we demonstrate the
      coexistence of optical modes with various degrees of localization (localized,
      extended and critical) and show that in-plane and out-of-plane optical energy
      confinement of extended critical modes can be optimally balanced. These results
      make aperiodic photonic structures very attractive for the engineering of novel
      passive and active photonic devices, such as low-threshold microlasers, sensitive
      detectors and bio-chemical sensors.

PMID- 19581971
TI  - Polychromatic liquid crystal laser arrays towards display applications.
AB  - Band-edge liquid crystal lasers are of interest for a number of applications
      including laser projection displays. Herein, we demonstrate simultaneous red
      green-blue lasing from a single liquid crystal sample by creating a two
      dimensional laser array fabricated from dye-doped chiral nematic liquid crystals.
      By forming a pitch gradient across the cell, and optically pumping the sample
      using a lenslet array, a polychromatic laser array can be observed consisting
      simultaneously of red-green-blue colors. Specifically, the two-dimensional
      polychromatic array could be used to produce a laser-based display, with low
      speckle and wide color gamut, whereby no complex fabrication procedure is
      required to generate the individual 'pixels'.

PMID- 19581972
TI  - High power cw and mode-locked oscillators based on Yb:KYW multi-crystal
      resonators.
AB  - We report on a high power diode-pumped laser using multiple bulk Yb:KY(WO(4))(2)
      (KYW) crystals in a resonator optimised for this operation. From a dual-crystal
      resonator we obtain more than 24 W of cw-power in a TEM(00) mode limited by the
      available pump power. We also present results for semiconductor saturable
      absorber mirror (SESAM) mode-locking in the soliton as well as positive
      dispersion regime with average output powers of 14.6 W and 17 W respectively.

PMID- 19581973
TI  - Picosecond polarized supercontinuum generation controlled by intermodal four-wave
      mixing for fluorescence lifetime imaging microscopy.
AB  - We present the generation of a picosecond polarized supercontinuum in highly
      birefringent multimodal microstructured fiber. The initial steps of the spectral
      broadening are dominated by intermodal four-wave mixing controlled by the
      specific fiber design. Using a low repetition rate ultra-stable solid state
      laser, a pulse train well-suited for versatile time-domain fluorescence lifetime
      imaging applications is obtained.

PMID- 19581974
TI  - Directionality of general beams.
AB  - The directionality of general beams propagating in free space and in atmospheric
      turbulence is studied. Based on the partial-coherence theory, the analytical
      expressions for the mean-squared width and the angular spread of general beams
      are derived by using the integral transform technique. It is shown that the mean
      squared width and the angular spread depend not only on the weighting factors of
      all basis modes but also on the weighting factors of the corresponding mode
      coherence coefficients of the ith and the (i+2)th if the Hermite-Gaussian modes
      are adopted. It is found that under a certain condition there exist the
      equivalent general beams which may have the same directionality as a fully
      coherent Gaussian beam in free space and also in atmospheric turbulence. The
      result holds true, irrespective of the model of turbulence used.

PMID- 19581975
TI  - Using four wavelength-multiplexed self-seeding Fabry-Perot lasers for 10 Gbps
      upstream traffic in TDM-PON.
AB  - In this paper, we propose and experimentally investigate a simple self-injection
      Fabry-Perot laser scheme on each optical network unit (ONU) for 10 Gbps TDM
      passive optical networks (PONs). Based on the proposed four wavelength
      multiplexed 2.5 Gbps lasers, the 10 Gbps uplink traffic can be achieved at a cost
      effective way. The network architecture and performance have also been analyzed
      and discussed.

PMID- 19581976
TI  - Ultrabroadband noncollinear optical parametric amplification with LBO crystal.
AB  - Ultrabroadband visible noncollinear optical parametric amplification (NOPA) was
      achieved in an LBO crystal, with a continuum seed pulse generated from a sapphire
      plate. The spectral bandwidth of the amplified visible pulse was about 200 nm,
      which can support sub-5 fs pulse amplification. An amplified output of 0.21
      microJ with an average gain of about 210 was achieved. This provides, to the best
      of our knowledge, the first-time demonstration of such broadband amplification
      with a biaxial nonlinear optical crystal. Both the simulation and experimental
      results indicate that the LBO has a great potential as nonlinear medium in power
      amplifier for TW to PW noncollinear optical parametric chirped pulse
      amplification (NOPCPA) systems.

PMID- 19581977
TI  - Diffraction limited amplification of picosecond pulses in 1170 microm2 effective
      area erbium fiber.
AB  - Robust fundamental mode propagation and amplification of picosecond pulses at
      1.56 microm wavelength is demonstrated in a core-pumped Er fiber with 1170
      microm2 effective area. Record peak power exceeding 120 kW, and 67 nJ pulse
      energy are achieved before the onset of pulse breakup. A small increase in input
      pulse energy results in a temporal collapse of the pulse center to 58 fs
      duration, with peak powers approaching 200 kW.

PMID- 19581978
TI  - Kerr-lens mode-locked Ti:sapphire laser with an additional intracavity nonlinear
      medium.
AB  - We demonstrate a Kerr-lens mode-locked Ti:sapphire laser with an additional
      Yb(3+) doped Potassium Yttrium Tungstate crystal (Yb:KYW) in the laser cavity,
      where not only the pump threshold to start mode-locking but also the stable
      regions to maintain mode-locking can be well-controlled by varying the position
      of Yb:KYW nearby the confocal focus to change the intracavity Kerr-effects. The
      pump threshold is reduced down to 800 mW to start the mode-locking operation,
      which is about 27% less than that for a Ti:sapphire laser without an additional
      Yb:KYW.

PMID- 19581979
TI  - Near- to far-field imaging of phase evolution of light emanating from a metal
      nanoslit.
AB  - We report near- to far-field measurement of optical wavefronts emanating from a
      nanoslit formed in a thin (50 nm thick) Ag film. The evolution of optical phases
      is imaged using a self-interference technique in conjunction with a scanning
      probe method. The phase relationship of the slit-transmitted waves with respect
      to the direct transmission through the thin metal film is quantitatively
      established. The singular-phase points resulting from the interplay of slit
      diffraction and surface plasmons are identified in the intermediate-field region.

PMID- 19581980
TI  - 40 Gbit/s asynchronous digital optical regenerator.
AB  - We present the first experimental demonstration of an asynchronous digital
      optical regenerator at 42.67 Gbit/s. The system effectively retimes incoming
      asynchronous data bursts to a local clock without burst mode clock recovery and
      converts the signal to a desired wavelength and duty cycle.

PMID- 19581981
TI  - Linear to radial polarization conversion in the THz domain using a passive
      system.
AB  - This paper addresses a passive system capable of converting a linearly polarized
      THz beam into a radially polarized one. This is obtained by extending to THz
      frequencies and waveguides an already proven concept based on mode selection in
      optical fibers. The approach is validated at 0.1 THz owing to the realization of
      a prototype involving a circular waveguide and two tapers that exhibits a
      radially polarized beam at its output. By a simple homothetic size reduction, the
      system can be easily adapted to higher THz frequencies.

PMID- 19581982
TI  - Poor man's source for sub 7 fs: a simple route to ultrashort laser pulses and
      their full characterization.
AB  - A practicable and economic method for the generation and full characterization of
      laser pulses ranging down to sub 7 fs duration with energies spanning the full
      microJ domain is presented. The method utilizes a self-induced and self-guiding
      filamentation of titanium-sapphire based, amplified pulses in air for spectral
      broadening, a standard chirp mirror compression scheme and transient grating
      frequency resolved optical gating for determining the spectral phase over the
      full visible to near infrared range. In this manner, few-cycle laser pulses with
      a high quality in the spatial beam profile have been generated in an robust
      arrangement with a minimal amount of standard optical components for their full
      characterization. The optical scheme demonstrates an uncomplicated, versatile
      access to this regime of pulsed laser radiation accompanied by a comprehensive
      analysis.

PMID- 19581983
TI  - Algorithm for multiple-beam Fizeau interferograms with arbitrary phase shifts.
AB  - The objective of this paper is to describe a novel method for phase extraction
      from multiple-beam Fizeau interferograms with arbitrary phase shifts. The
      approach begins with applying FFT method to estimate the phase shifts and then
      utilizes least-squares iterative algorithm to extract phase and phase shifts
      simultaneously. If the spatial carrier frequency of the fringes is high enough to
      separate the phase of the first-order maximum in the Fourier domain, the proposed
      method requires only two iterative cycles to accurately extract phase information
      from seven multiple-beam Fizeau interferograms with arbitrary phase shifts.
      Numerical simulations and experiments demonstrate the effectiveness of the
      proposed algorithm. A comprehensive analysis of the influences of systematic
      errors (spatial carrier frequency, reflectivity coefficient, and random noise) on
      the evaluation of phase shifts and phase is presented. The method has
      applications in high precision interferometry.

PMID- 19581984
TI  - Integration by self-aligned writing of nanocrystal/epoxy composites on InGaN
      micro-pixelated light-emitting diodes.
AB  - We report on the integration of monodisperse semiconductor nanocrystal (NC) color
      converters onto gallium nitride ultraviolet micro-pixelated light-emitting diodes
      ('micro-LEDs'). Integration is achieved in a 'self-aligned' process by forming a
      nanocomposite of the respective NCs in a photocurable epoxy polymer. Blue, green,
      yellow and red NC/epoxy blend microstructures have been successfully integrated
      onto micro-pixelated LEDs by this technique and utilised for color conversion,
      resulting in a five color emission single chip. Optical output power density of
      up to about 166 mW/cm2 is measured; spectral emission at 609 nm gives an
      estimated optical-to-optical conversion as high as 18.2% at 30 mA driving
      current.

PMID- 19581985
TI  - Pseudo-random tool paths for CNC sub-aperture polishing and other applications.
AB  - In this paper we first contrast classical and CNC polishing techniques in regard
      to the repetitiveness of the machine motions. We then present a pseudo-random
      tool path for use with CNC sub-aperture polishing techniques and report polishing
      results from equivalent random and raster tool-paths. The random tool-path used -
      the unicursal random tool-path - employs a random seed to generate a pattern
      which never crosses itself. Because of this property, this tool-path is directly
      compatible with dwell time maps for corrective polishing. The tool-path can be
      used to polish any continuous area of any boundary shape, including surfaces with
      interior perforations.

PMID- 19581986
TI  - CVD-diamond external cavity Raman laser at 573 nm.
AB  - Recent progress in diamond growth via chemical vapor deposition (CVD) has enabled
      the manufacture of single crystal samples of sufficient size and quality for
      realizing Raman laser devices. Here we report an external cavity CVD-diamond
      Raman laser pumped by a Q-switched 532 nm laser. In the investigated
      configuration, the dominant output coupling was by reflection loss at the
      diamond's uncoated Brewster angle facets caused by the crystal's inherent
      birefringence. Output pulses of wavelength 573 nm with a combined energy of 0.3
      mJ were obtained with a slope efficiency of conversion of up to 22%.

PMID- 19581987
TI  - Intense few-cycle light pulses in the deep ultraviolet.
AB  - We demonstrate that nonlinear frequency upconversion of few-cycle near-infrared
      (NIR) laser pulses, by means of harmonic generation in noble gases, is a
      promising approach for extending cutting-edge, few-cycle ultrafast technology
      into the deep ultraviolet and beyond, without the need for UV dispersion control.
      In our experiment, we generate 3.7-fs pulses in the deep UV (approximately 4.6
      eV) with adjustable polarization and gigawatt-scale peak power. We demonstrate
      that the implementation of this concept with a quasi-monocycle driver offers the
      potential for advancing UV pulse generation towards the 1-fs frontier.

PMID- 19581989
TI  - Engineered gratings for flat broadening of second-harmonic phase-matching
      bandwidth in MgO-doped lithium niobate waveguides.
AB  - Novel engineered step-chirped gratings (SCG) for broadband frequency converters
      based on quasi-phase matched second harmonic generation in MgO-doped lithium
      niobate waveguides have been theoretically modeled and simulated. It is shown
      mathematically that engineered apodized gratings can flatten the efficiency
      response. Also, it is verified that the bandwidth and flatness of an apodized SCG
      can be improved extensively with decreasing the number of segments and increasing
      the apodization ratio, respectively. Further, we show enhancing the minimum width
      of the line of the gratings to 1 micron for easing fabrication, almost all the
      beneficial effect on the efficiency response of an apodized SCG are maintained.
      The possibility of increasing the width of the poled lines and the increase in
      the chirp step due to use of the SCG structure, may provide more convenient route
      for fabrication and poling.

PMID- 19581988
TI  - Generation of laser-induced cavitation bubbles with a digital hologram.
AB  - We demonstrate a method using a spatial light modulator (SLM) to generate
      arbitrary 2-D spatial configurations of laser induced cavitation bubbles. The SLM
      acts as a phase hologram that controls the light distribution in the focal plane
      of a microscope objective. We generate cavitation bubbles over an area of 380 x
      380 microm(2) with a 20x microscope objective through absorption of the pulsed
      laser light in a liquid ink solution. We demonstrate the ability to accurately
      position up to 34 micrometer sized bubbles using laser energies of 56 microJ.

PMID- 19581990
TI  - Generation of large alkali vapor densities inside bare hollow-core photonic band
      gap fibers.
AB  - We demonstrate the ability to generate extremely large rubidium densities in
      uncoated hollow-core photonic band-gap fibers using light-induced atomic
      desorption. Once the fiber is exposed to Rb vapor for 1-2 weeks, and this atomic
      source is removed, the fiber yields large desorbable densities for an extended
      period of time. We show that optical depths greater than e(-1200) can be created
      within seconds. Our observed Rb densities are several orders of magnitude larger
      than any previously reported to be generated optically, and allow for the
      demonstration of a relatively easy-to-use fiber-based vapor cell capable of
      producing large optical depths without the need for thermal tuning.

PMID- 19581991
TI  - High-speed endless optical polarization stabilization using calibrated waveplates
      and field-programmable gate array-based digital controller.
AB  - A truly endless polarization stabilization experiment with a tracking speed of 15
      krad/s is presented. The high-speed polarization tracking is realized by using
      calibrated lithium niobate linear retardation waveplates as the polarization
      transformers combined with a very fast digital controller running on a field
      programmable gate array (FPGA).

PMID- 19581992
TI  - All-optical half adder based on cross structures in two-dimensional photonic
      crystals.
AB  - We propose an all-optical half adder based on two different cross structures in
      two-dimensional photonic crystals. One cross structure contains nonlinear
      materials and functions as an "AND" logic gate. The other one only contains
      linear materials and acts as an "XOR" logic gate. The system is demonstrated
      numerically by the FDTD method to work as expected. The optimal operating speed
      without considering the response time of the nonlinear material, the least ON to
      OFF logic-level contrast ratio, and the minimum power for this half adder
      obtained were 0.91 Tbps, 16 dB and 436 mW, respectively. The proposed structure
      has the potential to be used for constructing all-optical integrated digital
      computing circuits.

PMID- 19581993
TI  - Are negative index materials achievable with surface plasmon waveguides? A case
      study of three plasmonic geometries.
AB  - We present a theoretical analysis of planar plasmonic waveguides that support
      propagation of positive and negative index modes. Particular attention is given
      to the modes sustained by metal-insulator-metal (MIM), insulator-metal-insulator
      (IMI), and insulator-insulator-metal (IIM) geometries at visible and near
      infrared frequencies. We find that all three plasmonic structures are
      characterized by negative indices over a finite range of visible frequencies,
      with figures of merit approaching 20. Moreover, using finite-difference time
      domain simulations, we demonstrate that visible-wavelength light propagating from
      free space into these waveguides can exhibit negative refraction. Refractive
      index and figure-of-merit calculations are presented for Ag/GaP and Ag/Si(3)N(4) 
      based structures with waveguide core dimensions ranging from 5 to 50 nm and
      excitation wavelengths ranging from 350 nm to 850 nm. Our results provide the
      design criteria for realization of broadband, visible-frequency negative index
      materials and transformation-based optical elements for two-dimensional guided
      waves. These geometries can serve as basic elements of three-dimensional negative
      index metamaterials.

PMID- 19581994
TI  - Thermal wavelength stabilization of Bragg gratings photowritten in hole-filled
      microstructured optical fibers.
AB  - We demonstrate that the resonance wavelength of fiber Bragg gratings photowritten
      in the core of microstructured optical fibers can be efficiently stabilized
      versus temperature by inserting suitable refractive index materials with a
      negative thermal sensitivity into the holes. By these means, the effective index
      of the guided mode undergoes thermal variations which counterbalance the effect
      of the grating period thermal drift. The residual excursion of the resonance
      wavelength can be limited to less than +/- 10 pm over a 70 degrees C range of
      temperature into Microstructured Optical Fibers (MOFs) having realistic
      geometrical parameters, and using existing refractive index materials. Low cost
      passively stabilized reflectors with insertion loss lower than 0.3 dB can be
      realized by splicing single mode fibers at both ends of a short length of a
      filled MOF including the fiber Bragg grating.

PMID- 19581995
TI  - In-plane pitch control of cholesteric liquid crystals by formation of artificial
      domains via patterned photopolymerization.
AB  - A controlled helix pitch modulation in the in-plane direction of a planarly
      aligned cholesteric liquid crystal cell is demonstrated by using
      photopolymerizable cholesteric liquid crystals. By fabricating artificial domains
      with a closed volume via two-photon excitation laser-lithography, the degree of
      pitch modulation could be controlled by adjusting the surface area to volume
      ratio of the domain. A pitch modulation of over 60 nm was realized by designing
      the shape of the artificial domain.

PMID- 19581996
TI  - A 80 km reach fully passive WDM-PON based on reflective ONUs.
AB  - We propose a novel line coding combination (Inverse RZ coding in downlink and RZ
      in uplink) that extends the reach of WDM Passive Optical Networks based on
      Reflective SOAs with no in-line amplification. We achieved full downstream
      remodulation even when feeding the reflective SOA with power levels as low as -35
      dBm, thus increasing the system power budget. We experimentally assessed this
      scheme for a fully passive, full-duplex and symmetrical 1.25 Gb/s WDM-PON over a
      80 km G.652 feeder.

PMID- 19581997
TI  - Biofunctionalized tilted Fiber Bragg Gratings for label-free immunosensing.
AB  - We present a study aimed at developing a label-free optical fiber biosensor for
      detection and quantification of biomolecules in real-time. The biosensor based on
      a Tilted Fiber Bragg Grating (TFBG) transduces a binding event between the probe
      and target molecules into a change in the refractive index of the medium
      surrounding the fiber. This work describes the experimental results obtained with
      three methods for immobilizing biomolecular probes on a TFBG silica cladding
      surface. Bovine serum albumin (BSA) and anti-BSA are used to assess the
      performances of the TFBG based biosensor in each configuration.

PMID- 19581998
TI  - Transmission performance of a wavelength and NRZ-to-RZ format conversion with
      pulsewidth tunability by combination of SOA- and fiber-based switches.
AB  - An all-optical signal processing scheme coupling wavelength conversion and NRZ-to
      RZ data format conversion with pulsewidth tunability into one by combination of
      SOA- and fiber-based switches, is experimentally demonstrated, and its
      transmission performance is investigated. An 1558 nm NRZ data signal is converted
      to RZ data format at 1546 nm with widely tunable pulsewidth from 20 % to 80 %
      duty cycle at the bit-rate of 10 Gb/s. The investigation on transmission
      performance of the converted RZ signals at each different pulsewidth is carried
      out over various standard single-mode fiber (SSMF) links up to 65 km long without
      dispersion compensation. The results clarify a significant improvement on
      transmission performance of converted signal in comparison with the conventional
      NRZ signal through tunable pulsewidth management and show the existence of an
      optimal pulsewidth for the RZ data format at each transmission distance with
      particular cumulative dispersion. The optimal pulsewidths of the converted RZ
      signal and its corresponding power penalties against the NRZ signal are also
      investigated in different SSMF links.

PMID- 19581999
TI  - Cross talk free multi channel processing of 10 Gbit/s data via four wave mixing
      in a 1550 nm InAs/InP quantum dash amplifier.
AB  - We demonstrate multi wavelength processing in a broad band 1550 nm quantum dash
      optical amplifier. Two 10 Gbit/s signals, spectrally separated by 30 nm are
      individually wavelength converted via four wave mixing (FWM) with no cross talk.
      High power signal levels cause depletion of high energy and wetting layer states
      resulting in some homogenizing of the gain medium and generation of cross FWM
      components near each channel due to FWM in the other channel. These do not affect
      the cross-talkless multichannel processing except when the two channels use equal
      detuning between signal and pump.

PMID- 19582000
TI  - Apodized SCISSORs for filtering and switching.
AB  - This paper presents 1550-nm simulation results on the waveguided silicon-on
      insulator four-port optical filtering and switching devices known as "SCISSOR"
      (an in-line array of microring resonators wherein each ring is coupled to two bus
      waveguides). We optimized the array number, the ring-bus coupling and the inter
      ring spacing in order to obtain "rectangular" filter-passband shapes that have
      not heretofore been reported in the resonant-optics literature. We were able to
      engineer a box-like bandpass whose wavelength width could be anywhere from 5 to
      50 % of the free spectral range (FSR). We then performed ring-bus apodization of
      the array that increased side-lobe suppression on the main filter band and
      widened the band. By reducing the FSR to 2.51 nm with increased ring diameter, we
      also showed that complete, high-extinction 2 x 2 optical switching is attained
      when the effective index of each ring in the group is changed by 2 x 10(-3),
      giving 1.02-nm shift of the 0.77-nm passband. Tunable filtering, sensing,
      reconfigurable add/drop and wavelength-division demultiplexing is offered in
      addition to switching.

PMID- 19582001
TI  - Surface wave splitter based on metallic gratings with sub-wavelength aperture.
AB  - We investigated the splitting of surface electromagnetic waves trapped at the
      output surface of a one-dimensional metallic grating structure. The output
      gratings of the structure asymmetrically such that the output surfaces at the
      different sides of the subwavelength aperture can support surface waves at
      different frequencies. The transmission amplitude as measured at the left side is
      1,000 times of that at the right side at 16 GHz. At 24 GHz, the transmission
      measured at the right side is 20 times that of the left side of the structure.
      Therefore, surface waves are guided into the different sides of the aperture at
      different frequencies via metallic gratings. The experimental results are in
      agreement with the theoretical results.

PMID- 19582002
TI  - Analysis of optical pulse coding in spontaneous Brillouin-based distributed
      temperature sensors.
AB  - A theoretical and experimental analysis of optical pulse coding techniques
      applied to distributed optical fiber temperature sensors based on spontaneous
      Brillouin scattering using the Landau-Placzek ratio (LPR) scheme is presented,
      quantifying in particular the impact of Simplex coding on stimulated Brillouin
      and Raman power thresholds. The signal-to-noise ratio (SNR) enhancement and
      temperature resolution improvement provided by coding are also characterized.
      Experimental results confirm that, differently from Raman-based sensors, pulse
      coding affects the stimulated Brillouin threshold, resulting in lower optimal
      input power levels; these features allow one to achieve high sensing performance
      avoiding the use of high peak power pulses.

PMID- 19582003
TI  - Optical switching mediated by quantum interference of Raman transitions.
AB  - We report an experimental study of quantum interference between two-photon Raman
      transitions and demonstration of the phase control of light
      attenuation/transmission in cold Rb atoms. By varying the phase and frequency of
      a weak control laser, either constructive interference or destructive
      interference between the two-photon Raman transitions in a three-level Lambda
      system can be manipulated. The interference enables absorptive switching of one
      field by another field at low light levels.

PMID- 19582004
TI  - Long-distance entanglement-based quantum key distribution over optical fiber.
AB  - We report the first entanglement-based quantum key distribution (QKD) experiment
      over a 100-km optical fiber. We used superconducting single photon detectors
      based on NbN nanowires that provide high-speed single photon detection for the
      1.5-mum telecom band, an efficient entangled photon pair source that consists of
      a fiber coupled periodically poled lithium niobate waveguide and ultra low loss
      filters, and planar lightwave circuit Mach-Zehnder interferometers (MZIs) with
      ultra stable operation. These characteristics enabled us to perform an
      entanglement-based QKD experiment over a 100-km optical fiber. In the experiment,
      which lasted approximately 8 hours, we successfully generated a 16 kbit sifted
      key with a quantum bit error rate of 6.9 % at a rate of 0.59 bits per second,
      from which we were able to distill a 3.9 kbit secure key.

PMID- 19582005
TI  - Generation and control of hot spots on commensurate metallic gratings.
AB  - We study the light localization on commensurate arrangements of deep metallic sub
      wavelength grooves. We theoretically show that as the degree of commensuration
      tends to an irrational number new light localization states are produced. These
      have properties close to that reported for hot spots on disordered surfaces and
      are not permitted for simple period gratings. Existence of these new resonances
      is experimentally provided in the infra-red region by reflectivity measurements
      performed on two commensurate samples with respectively two and three slits per
      period. Manipulations of these hot spots which can be controlled from far-field
      could be used for high sensitivity spectroscopy applications.

PMID- 19582006
TI  - Design of a silicon nitride photonic crystal nanocavity with a Quality factor of
      one million for coupling to a diamond nanocrystal.
AB  - A photonic crystal nanocavity with a Quality (Q) factor of 1.4 x 10(6), a mode
      volume of 0.78(lambda/n)(3), and an operating wavelength of 637 nm is designed in
      a silicon nitride (SiN(x)) ridge waveguide with refractive index of 2.0. The
      effect on the cavity Q factor and mode volume of single diamond nanocrystals of
      various sizes and locations embedded in the center and on top of the nanocavity
      is simulated, demonstrating that Q > 1 x 10(6) is achievable for realistic
      parameters. An analysis of the figures of merit for cavity quantum
      electrodynamics reveals that strong coupling between an embedded diamond nitrogen
      vacancy center and the cavity mode is achievable for a range of cavity
      dimensions.

PMID- 19582007
TI  - Spectroscopic and lasing performance of Tm3+-doped bulk TZN and TZNG tellurite
      glasses operating around 1.9 microm.
AB  - We report spectroscopic and bulk laser performance characteristics for Tm(3+)
      doped tellurite glasses when used as gain media operating around 1.9 microm. Two
      glass hosts studied are TZN and TZNG and their performances have been compared.
      In each case, well-characterized cw laser performance was obtained and this has
      been related to detailed spectroscopic measurements of the important lasing
      parameters of the laser transitions around 1900 nm when pumped at 793 nm. The
      maximum output power achieved was 124 mW from the TZNG sample with an associated
      slope efficiency of 28 % with a tuning range of 135 nm. Efficiency and loss
      analyses yielded a calculated maximum attainable efficiency of 48 % in Tm(3+):TZN
      compared to 28 % for the TZNG host.

PMID- 19582008
TI  - Correct definition of the Poynting vector in electrically and magnetically
      polarizable medium reveals that negative refraction is impossible.
AB  - I compute from first principles the local heating rate q (the amount of
      electromagnetic energy converted to heat per unit time per unit volume) for
      electromagnetic waves propagating in magnetically and electrically polarizable
      media. I find that, in magnetic media, this rate has two separate contributions,
      q(V) and q(S), the first coming from the volume of the medium and the second from
      its surface. I argue that the second law of thermodynamics requires that the
      volume contribution be positive and that this requirement, in turn, prohibits
      negative refraction. This result holds for active or passive media and in the
      presence of anisotropy and spatial dispersion.

PMID- 19582010
TI  - Deep microstructure topography characterization with optical vortex
      interferometer.
AB  - We report on a new method of inspecting deep microstructures manufactured in
      transparent media. Although their lateral dimension (tens of microns) do not
      exceed the diffraction limit for optical microscopy resolution, their deepness
      makes the nondestructive measurements practically impossible with presently
      available methods. We show that the optical vortex interferometer with a vortex
      generator can be used to differentiate between the samples of good and poor
      quality. The measurement system is simple and the interpretation of the results
      is straightforward.

PMID- 19582009
TI  - Fiber Bragg grating inscription combining DUV sub-picosecond laser pulses and two
      beam interferometry.
AB  - The combination of fiber Bragg grating inscription with femtosecond laser sources
      and the usage of the Talbot interferometer setup not only gives access to the
      fabrication of Bragg gratings in new types of materials but also allows, at the
      same time, to keep the high flexibility of an interferometric setup in choosing
      the Bragg grating wavelength. Since the spatial and temporal coherence properties
      of the femtosecond laser source differ strongly from those of conventional laser
      sources, specific limits and tolerances in the interferometric setup have to be
      considered. Such limits are investigated on the basis of an analytical ray
      tracing model. The results are applied to tolerance measurements of fiber Bragg
      grating reflections recorded with a DUV sub-picosecond laser source at 262 nm.
      Additionally we demonstrate the wavelength versatility of the two-beam
      interferometer setup for femtosecond inscription over a 40 nm wavelength band.
      Inscription experiments in Al/Yb doped silica glasses are demonstrated as a prove
      for the access to non-photosensitive fibers.

PMID- 19582011
TI  - Image restoration for fluorescence lifetime imaging microscopy (FLIM).
AB  - Computational image restoration finds wide applicability for fluorescence
      intensity imaging. Relatively little work in this regard has been performed on
      FLIM images, which also suffer from diminished spatial resolution. In this work,
      we report two separate approaches to enhance FLIM image quality while maintaining
      lifetime accuracy. A 2D-image restoration algorithm was employed to improve
      resolution in gated intensity images of various samples including fluorescent
      beads, living cells and fixed tissue samples. The restoration approach improved
      lifetime image quality without significant variation in lifetime. Further,
      overlaying a restored-intensity image over the native lifetime image provided
      even better results, where the resulting lifetime map had spatial features
      similar to the intensity map. 2D and 3D image restoration also benefit from
      advances in computational power and hence holds potential for enhancing FLIM
      resolution, particularly in ICCD-based wide-field FLIM systems, without
      sacrificing vital quantitative information.

PMID- 19582012
TI  - Quantum dot dipole orientation and excitation efficiency of micropillar modes.
AB  - The relative intensity of photonic modes in microcavity pillars with embedded
      self-assembled quantum dots is shown to be a sensitive function of quantum dot
      dipole orientation and position. This is deduced from a comparison of experiment
      and calculated intensities of light emission for many nominally identical
      pillars. We are able to obtain the overall degree of in-plane polarization of the
      quantum dot ensemble and also to obtain information on the degree of polarization
      along the growth axis.

PMID- 19582013
TI  - Generation of an incident focused light pulse in FDTD.
AB  - A straightforward procedure is described for accurately creating an incident
      focused light pulse in the 3-D finite-difference time-domain (FDTD)
      electromagnetic simulation of the image space of an aplanatic converging lens. In
      this procedure, the focused light pulse is approximated by a finite sum of plane
      waves, and each plane wave is introduced into the FDTD simulation grid using the
      total-field/scattered-field (TF/SF) approach. The accuracy of our results is
      demonstrated by comparison with exact theoretical formulas.

PMID- 19582014
TI  - Scaling of passively mode-locked soliton erbium waveguide lasers based on slow
      saturable absorbers.
AB  - We assess the scaling potential of high repetition rate, passively mode-locked
      erbium-doped soliton lasers. Our analysis focuses on three recently demonstrated
      lasers using saturable Bragg reflectors (SBR) as the mode-locking element. We use
      the soliton Area theorem to establish the limitations to increasing the
      repetition rate based on insufficient intracavity pulse energy, SBR properties,
      and dispersion engineering. Finally, we examine possible approaches to alleviate
      these limitations by changing the laser's structure and composition.

PMID- 19582015
TI  - High-resolution Fourier-transform cavity-enhanced absorption spectroscopy in the
      near-infrared using an incoherent broad-band light source.
AB  - An incoherent broad-band cavity-enhanced absorption (IBB-CEA) set-up was used in
      combination with a Fourier-transform (FT) spectrometer in order to explore the
      potential of this technique for high-resolution molecular spectroscopy in the
      near-infrared region. Absorption spectra of overtone bands of CO2, OCS, and HD18O
      were measured between 5800 and 7000 cm(-1) using a small sampling volume (1100
      cm3, based on a 90 cm cavity length). The quality of the spectra in this study is
      comparable to that obtained with Fourier transform spectrometers employing
      standard multi-pass reflection cells, which require substantially larger sampling
      volumes. High-resolution methods such as FT-IBB-CEAS also provide an elegant way
      to determine effective mirror reflectivities (R(eff), i.e. a measure of the
      inherent overall cavity loss) by using a calibration gas with well-known line
      strengths. For narrow absorption features and non-congested spectra this approach
      does not even require a zero-absorption measurement with the empty cavity.
      Absolute cross-sections or line strengths of a target species can also be
      determined in one single measurement, if gas mixtures with known partial
      pressures are used. This feature of FT-IBB-CEAS reduces systematic errors
      significantly; it is illustrated based on CO2 as calibration gas.

PMID- 19582016
TI  - Nonresonant high-order nonlinear optical properties of silver nanoparticles in
      aqueous solution.
AB  - In this work we determine the third, fifth- and seventh-order nonresonant
      nonlinear optical properties of silver nanoparticles (9 nm average diameter)
      colloids in aqueous solution under high intensity excitation. The nonlinear
      optical response and its dependence with the nanoparticles filling factor was
      measured and theoretically described. We show that for low inclusion
      concentration, the third order nonlinearity of the colloid can be described by
      the generalized Maxwell-Garnett model. With the increase of the nanoparticle
      concentration, changes in the medium nonlinearities was observed leading to high
      order effects. The fifth- and seventh- order susceptibilities were obtained for
      highly concentrated silver nanoparticle colloid and the data was supported by a
      theoretical model. The conventional Z-scan technique was employed, using 80 f s
      laser pulses at 800 nm, in a regime of high pulse energy (microJ) and low
      repetition rate (1 kHz).

PMID- 19582017
TI  - Detection of fluorescent-labeled probes at subpicomolar concentrations by
      magnetic modulation.
AB  - A sensitive and rapid method for detecting fluorescent dyes at low concentrations
      in homogenous solution is experimentally demonstrated. Fluorescent-labeled DNA
      probes are detected by attaching magnetic beads and applying alternating magnetic
      field gradient. This condenses the fluorescent probes into a small detection
      volume and eliminates the scattering noise from solution by synchronous
      detection. For DNA probes concentration of 1 x 10(-13) M the detection signal was
      3.3 times higher than the noise, thereby implying detection sensitivity of 3 x
      10(-14) M.

PMID- 19582018
TI  - Superresolution digital holographic microscopy for three-dimensional samples.
AB  - An approach that allows superresolution imaging of three-dimensional (3-D)
      samples by numerical refocusing is presented in the field of digital holographic
      microscopy. Based on the object's spectrum shift produced by tilted illumination,
      we present a time multiplexing superresolved approach to overcome the Abbe's
      diffraction limit. The proposed approach uses a microscope in a Mach-Zehnder
      interferometric architecture with the particularity that the output plane does
      not coincide with the image plane. Thus, a set of off-axis non-image plane
      holograms are sequentially recorded for every tilted beam used in the
      illumination stage. After that and by using simple digital post-processing and
      numerical reconstruction, a 3-D superresolved sample volume is reconstructed
      slice-by- slice in terms of the definition of a synthetic aperture (SA) that
      expands the cutoff frequency of the microscope lens. Experimental results showing
      the capabilities of the proposed approach are presented.

PMID- 19582019
TI  - Phase modulation of surface plasmon polaritons by surface relief dielectric
      structures.
AB  - Phase modulation of surface plasmon polaritons (SPPs) is studied as a function of
      geometric length and thickness of surface relief dielectric structures on a metal
      film. The results indicate that the SPPs are analogous to conventional free-space
      light waves in terms of phase modulation by geometric sizes and refractive
      indices. An SPP Fresnel zoneplate is considered as an example to employ the phase
      modulation method for focusing enhancement at the focal point. It is found that
      the phase modulation optimized zoneplate has obtained 130% higher electric field
      intensity at the focal point than that of an amplitude-modulated zoneplate.

PMID- 19582020
TI  - Achieving high focusing power for a large-aperture liquid crystal lens with novel
      hole-and-ring electrodes.
AB  - Aiming to equip commercial camera modules, such as the optical imaging systems
      with a CMOS sensor module in 3 Mega pixels, an ultra thin liquid crystal lens
      with designed hole-and-ring electrodes is proposed in this study to achieve high
      focusing power. The LC lens with proposed electrodes improves the central
      intensity of electric field which leads to better focusing quality. The overall
      thickness of the LC lens can be as thin as 1.2 mm and the shortest focal length
      of the 4 mm-aperture lens occurs at 20 cm under an applied voltage of 30 V at 1
      KHz. The inner ring electrode requires only 40% of applied voltage of the
      external hole electrode. The applied voltages for this internal ring and external
      hole electrodes can simply be realized by a pre-designed parallel resistance pair
      and a single voltage source. Experiments are conducted for validation and it
      shows that the designed LC lens owns good image clearness and contrast at the
      focal plane. The proposed design reduces the thickness of LC lens and is capable
      of achieving relative higher focusing power than past studies with lower applied
      voltage.

PMID- 19582021
TI  - Modeling of Rabi splitting in quantum well microcavities using time-dependent
      transfer matrix method.
AB  - Rabi splitting in quantum well (QW) embedded in microcavities under strong
      coupling condition is modeled by a time-dependent transfer matrix model. The
      spectral response of QW under the influence of excitonic effects is simulated by
      infinite impulse digital filters. It is shown that the splitting energy obtained
      from the proposed model match well with that deduced from the reflection spectrum
      analysis. The lasing spectra observed from different transmission angles of the
      QW microcavity can also be calculated. Hence, it is proved that the proposed
      model can be used to design and analyze the lasing characteristics of QW
      microcavities under strong coupling condition.

PMID- 19582022
TI  - Temperature- and phase-independent lateral force sensor based on a core-offset
      multi-mode fiber interferometer.
AB  - A novel lateral force sensor based on a core-offset multi-mode fiber (MMF)
      interferometer is reported. High extinction ratio can be obtained by misaligning
      a fused cross section between the single-mode fiber (SMF) and MMF. With the
      variation of the lateral force applied to a short section of the MMF, the
      extinction ratio changes while the interference phase remains almost constant.
      The change of the extinction ratio is independent of temperature variations. The
      proposed force sensor has the advantages of temperature- and phase-independency,
      high extinction ratio sensitivity, good repeatability, low cost, and simple
      structure. Moreover, the core-offset MMF interferometer is expected to have
      applications in fiber filters and tunable phase-independent attenuators.

PMID- 19582023
TI  - Inscription of fibre Bragg gratings in non-sensitised fibres using VUV F2 laser
      radiation.
AB  - We report the inscription of fibre Bragg gratings in non-sensitised SMF 28 and HI
      980 fibre by exposure to VUV F2 laser radiation at 157 nm. The modulated
      effective refractive index change Deltan(eff) deduced from the shift in the
      grating reflection peaks was Deltan(eff) = 2.8x10(-4) and 1.7x10(-4) in SMF 28
      and HI 980 fibre respectively. The possible influence of non-uniformity of core
      exposure and VUV cladding absorption loss on these results is discussed.

PMID- 19582024
TI  - Enhanced antireflecting properties of micro-structured top-flat pyramids.
AB  - This paper aims at modeling bi-periodic micro-structured silicon surfaces
      exhibiting broadband antireflection properties in the infrared range using
      Rigorous Coupled-Wave Analysis (RCWA). These structures of pyramidal shape, which
      typical dimensions are smaller than the wavelength, are not in the Effective
      Medium Theory (EMT) validity domain. The influence of various opto-geometrical
      parameters such as period, depth, shape of the pattern is examined. The
      antireflective properties of such bi-periodic patterned surfaces are then
      discussed using the photonic crystal theory and photonic band diagrams
      description. Correlations between the density of Bloch modes, their localizations
      with respect to the incident medium light line and the surface reflectance are
      presented.

PMID- 19582025
TI  - Intercomparison of two BRDF models in the estimation of the directional
      emissivity in MIR channel from MSG1-SEVIRI data.
AB  - This work intercompared two Bi-directional Reflectance Distribution Function
      (BRDF) models, the modified Minnaert's model and the RossThick-LiSparse-R model,
      in the estimation of the directional emissivity in Middle Infra-Red (MIR) channel
      from the data acquired by the Spinning Enhanced Visible and Infra-Red Imager
      (SEVIRI) onboard the first Meteosat Second Generation (MSG1). The bi-directional
      reflectances in SEVIRI channel 4 (3.9 microm) were estimated from the combined
      MIR and Thermal Infra-Red (TIR) data and then were used to estimate the
      directional emissivity in this channel with aid of the BRDF models. The results
      show that: (1) Both models can relatively well describe the non-Lambertian
      reflective behavior of land surfaces in SEVIRI channel 4; (2) The RossThick
      LiSparse-R model is better than the modified Minnaert's model in modeling the bi
      directional reflectances, and the directional emissivities modeled by the
      modified Minnaert's model are always lower than the ones obtained by the
      RossThick-LiSparse-R model with averaged emissivity differences of approximately
      0.01 and approximately 0.04 over the vegetated and bare areas, respectively. The
      use of the RossThick-LiSparse-R model in the estimation of the directional
      emissivity in MIR channel is recommended.

PMID- 19582026
TI  - Dissipative solitons in a passively mode-locked Er-doped fiber with strong normal
      dispersion.
AB  - We report on ultrashort pulse generation from a passively mode-locked erbium
      fiber laser operating in the highly positive dispersion regime. Highly-chirped
      pulses with 5.3 ps duration and spectral bandwidth of 8.3 nm are generated. They
      are extra-cavity compressed down to 757 fs. Numerical simulations confirm the
      experimental results and show that these pulses could be interpreted as
      dissipative solitons.

PMID- 19582027
TI  - Phase shifts in the Fourier spectra of phase gratings and phase grids: an
      application for one-shot phase-shifting interferometry.
AB  - Among several techniques, phase shifting interferometry can be implemented with a
      grating used as a beam divider to attain several interference patterns around
      each diffraction order. Because each pattern has to show a different phase-shift,
      a suitable shifting technique must be employed. Phase gratings are attractive to
      perform the former task due to their higher diffraction efficiencies. But as is
      very well known, the Fourier coefficients of only-phase gratings are integer
      order Bessel functions of the first kind. The values of these real-valued
      functions oscillate around zero, so they can adopt negative values, thereby
      introducing phase shifts of pi at certain diffraction orders. Because this almost
      trivial fact seems to have been overlooked in the literature regarding its
      practical implications, in this communication such phase shifts are stressed in
      the description of interference patterns obtained with grating interferometers.
      These patterns are obtained by placing two windows in the object plane of a 4f
      system with a sinusoidal grating/grid in the Fourier plane. It is shown that the
      corresponding experimental observations of the fringe modulation, as well as the
      corresponding phase measurements, are all in agreement with the proposed
      description. A one-shot phase shifting interferometer is finally proposed taking
      into account these properties after proper incorporation of modulation of
      polarization.

PMID- 19582028
TI  - Energy considerations for a superlens based on metal/dielectric multilayers.
AB  - We investigate the resolution and absorption losses of a Ag/GaP multilayer
      superlens. For a fixed source to image distance the resolution is independent of
      the position of the lens but the losses depend strongly on the lens placement.
      The absorption losses associated with the evanescent waves can be significantly
      larger than losses associated with the propagating waves especially when the
      superlens is close to the source. The interpretation of transmittance values
      greater than unity for evanescent waves is clarified with respect to the
      associated absorption losses.

PMID- 19582029
TI  - Large area uniform nanostructures fabricated by direct femtosecond laser
      ablation.
AB  - An approach for fabricating large area uniform nanostructures by direct
      femtosecond (fs) laser ablation is presented. By the simple scanning technique
      with appropriate irradiation conditions, arbitrary size of uniform, complanate
      nano-grating, nano-particle, and nano-square structures can be produced on wide
      bandgap materials as well as graphite. The feature sizes of the formed
      nanostructures, which can be tuned in a wide range by varying the irradiation
      wavelength, is about 200 nm with 800 nm fs laser irradiation. The physical
      properties of the nano-structured surfaces are changed greatly, especially the
      optical property, which is demonstrated by the extraordinary enhancement of light
      transmission of the treated area. This technique is efficient, universal, and
      environmentally friendly, which exhibits great potential for applications in
      photoelectron devices.

PMID- 19582030
TI  - Two-dimensional electromagnetic cloaks with non-conformal inner and outer
      boundaries.
AB  - Transformation optics is extended to the design of two-dimensional (2D) cloaks
      with non-conformal inner and outer boundaries. General and explicit expressions
      of the transformed medium parameters are derived, which are of the utmost
      importance in a cloak design procedure. A 2D cloak with irregular and non
      conformal boundaries is designed as an example. Full-wave simulations combined
      with Huygens' Principle are applied to verify the invisibility of the cloak to
      external incident waves. All the theoretical and numerical results verify the
      effectiveness of the proposed method. The generalization in this Paper highly
      improves the flexibilities for cloak design.

PMID- 19582031
TI  - Photonic crystal fiber with a dual-frequency addressable liquid crystal: behavior
      in the visible wavelength range.
AB  - Wave-guiding in the visible spectral range is investigated for a micro-structured
      crystal fiber filled with a dual-frequency addressable nematic liquid crystal
      mixture. The fiber exhibits a solid core surrounded by just 4 rings of
      cylindrical holes. Control of the liquid crystal alignment by anchoring agents
      permits relatively low attenuation. Samples with different anchoring conditions
      at the interface of the silica glass and the liquid crystal show different
      transmission properties and switching behavior. Polarization dependent and
      independent fiber optic switching is observed. Due to a dualfrequency addressing
      scheme, active switching to both states with enhanced and reduced transmission
      becomes possible for planar anchoring. Even a non-perfect fiber shows reasonable
      transmission and a variety of interesting effects.

PMID- 19582032
TI  - Multi-channel notch filter based on a phase-shift phase-only-sampled fiber Bragg
      grating.
AB  - We propose a novel method for the implementation of a tunable multi-channel notch
      filter based on a thermally induced phase-shift phase-only sampled fiber Bragg
      grating (FBG). The proposed method is numerically and experimentally
      demonstrated. A 51-channel notch filter with a bandwidth (FWHM) of 0.026 nm and a
      tuning range of 0.6 nm has been achieved. This proposed technique offers the
      potential applications to the multiwavelength fiber laser and multi-channel all
      optical logic devices.

PMID- 19582036
TI  - Threshold of a random laser based on Raman gain in cold atoms.
AB  - We address the problem of achieving a random laser with a cloud of cold atoms, in
      which gain and scattering are provided by the same atoms. In this system, the
      elastic scattering cross-section is related to the complex atomic polarizability.
      As a consequence, the random laser threshold is expressed as a function of this
      polarizability, which can be fully determined by spectroscopic measurements. We
      apply this idea to experimentally evaluate the threshold of a random laser based
      on Raman gain between non-degenerate Zeeman states and find a critical optical
      thickness on the order of 200, which is within reach of state-of-the-art cold
      atom experiments.

PMID- 19582037
TI  - Theory for n-type doped, tensile-strained Ge-Si(x)Ge(y)Sn1-x-y quantum-well
      lasers at telecom wavelength.
AB  - We propose and develop a theoretical gain model for an n-doped, tensile-strained
      Ge-Si(x)Ge(y)Sn(1-x-y) quantum-well laser. Tensile strain and n doping in Ge
      active layers can help achieve population inversion in the direct conduction band
      and provide optical gain. We show our theoretical model for the bandgap
      structure, the polarization-dependent optical gain spectrum, and the free-carrier
      absorption of the n-type doped, tensile-strained Ge quantum-well laser. Despite
      the free-carrier absorption due to the n-type doping, a significant net gain can
      be obtained from the direct transition. We also present our waveguide design and
      calculate the optical confinement factors to estimate the modal gain and predict
      the threshold carrier density.

PMID- 19582039
TI  - Single-trench waveguide TE-TM mode converter.
AB  - A TE-TM mode converter is proposed in a single trench GaInAsP/InP waveguide,
      which is fabricated by a single masking and etching process. Use of single-trench
      structure makes the design and the fabrication much simpler. The design of single
      trench mode converter is described together with its fabrication in this article.
      We investigated the dependence of conversion efficiency on the waveguide width,
      trench depth, and trench position. Also, the wavelength dependence of mode
      conversion efficiency was calculated in a wavelength range between 1.5 microm to
      1.58 microm. 95% TE-TM mode conversion was measured at a wavelength of 1.55
      microm in a fabricated device with a 210-microm half-beat length.

PMID- 19582038
TI  - Single-pulse coherent anti-Stokes Raman scattering microscopy employing an octave
      spanning pulse.
AB  - We demonstrate two complementary types of microscopy using an identical setup for
      single-pulse coherent anti-Stokes Raman scattering (CARS) imaging, which employs
      an ultrabroadband laser pulse with a spectral bandwidth of 4800 cm(-1) and
      enables the suppression of nonresonant CARS signals. One is a novel type of
      microscopy that uses spectral phase modulation for the selective excitation of a
      single Raman mode. The selective excitation is achieved by the modulated pulse
      focusing its difference-frequency spectrum into a narrow spectral region. Another
      type is Fourier-transform CARS (FT-CARS) microspectroscopy based on the
      measurement of the CARS spectrum obtained from the Fourier-transform of the
      interferometric autocorrelation (IAC) signal. Vibrational spectral imaging of
      chemical and biological samples is demonstrated using the two types of
      microscopy.

PMID- 19582040
TI  - Continuous-wave Lyman-alpha generation with solid-state lasers.
AB  - A coherent continuous-wave Lyman-alpha source based on four-wave sum-frequency
      mixing in mercury vapor has been realized with solid-state lasers. The third
      order nonlinear susceptibility is enhanced by the 6(1)S - 7(1)S two-photon
      resonance and the near 6(1)S-6(3)P one-photon resonance. The phase matching curve
      for this four-wave mixing scheme is observed for the first time. In addition we
      investigate the two-photon enhancement of the Lyman-alpha yield and observe that
      the maxima of Lyman-alpha generation are shifted compared to the two-photon
      resonances of the different isotopes.

PMID- 19582041
TI  - Demonstrations of analog-to-digital conversion using a frequency domain stretched
      processor.
AB  - The first proof-of-concept demonstrations are presented for a broadband photonic
      assisted analog-to-digital converter (ADC) based on spatial spectral holography
      (SSH). The SSH-ADC acts as a frequency-domain stretch processor converting high
      bandwidth input signals to low bandwidth output signals, allowing the system to
      take advantage of high performance, low bandwidth electronic ADCs. Demonstrations
      with 50 MHz effective bandwidth are shown to highlight basic performance with
      approximately 5 effective bits of vertical resolution. Signal capture with 1600
      MHz effective bandwidth is also shown. Because some SSH materials span over 100
      GHz and have large time apertures (approximately 10 micros), this technique holds
      promise as a candidate for the next generation of ADCs.

PMID- 19582042
TI  - Nano-manipulation of diamond-based single photon sources.
AB  - The ability to manipulate nano-particles at the nano-scale is critical for the
      development of active quantum systems. This paper presents a technique to
      manipulate diamond nano-crystals at the nano-scale using a scanning electron
      microscope, nano-manipulator and custom tapered optical fibre probes. The
      manipulation of a approximately 300 nm diamond crystal, containing a single
      nitrogen-vacancy centre, onto the endface of an optical fibre is demonstrated.
      The emission properties of the single photon source post manipulation are in
      excellent agreement with those observed on the original substrate.

PMID- 19582043
TI  - A field theoretical restoration method for images degraded by non-uniform light
      attenuation : an application for light microscopy.
AB  - Microscopy has become a de facto tool for biology. However, it suffers from a
      fundamental problem of poor contrast with increasing depth, as the illuminating
      light gets attenuated and scattered and hence can not penetrate through thick
      samples. The resulting decay of light intensity due to attenuation and scattering
      varies exponentially across the image. The classical space invariant
      deconvolution approaches alone are not suitable for the restoration of uneven
      illumination in microscopy images. In this paper, we present a novel physics
      based field theoretical approach to solve the contrast degradation problem of
      light microscopy images. We have confirmed the effectiveness of our technique
      through simulations as well as through real field experimentations.

PMID- 19582044
TI  - 193nm Superlens imaging structure for 20nm lithography node.
AB  - We are showing that a 20nm lithography resolution is theoretically feasible at a
      193nm illumination wavelength if employing aluminum (Al) superlens structure with
      index matching layer. It is illustrated that transmissivity of evanescent waves
      for certain wavevector bands can be enhanced by an index matching layer. It is
      further shown a minimal resolution of approximately lambda/10 can be achieved by
      appropriately engineering mask material and superlens structure. A depth of focus
      of several nanometers is predicted to be possible for a periodic structure with
      20nm half pitch. Assistant features were adopted in superlens structure to
      successfully suppress the side lobes and resolve a 20nm two-slit structure.

PMID- 19582045
TI  - Surface plasmon converging and diverging properties modulated by polymer
      refractive structures on metal films.
AB  - Polymer refractive microstructures are fabricated on metallic thin films and
      employed to modulate surface plasmons (SPs) propagations in a refractive manner.
      SP waves converging with different focal lengths and diverging effects are
      realized by the refractive structures. Authors investigated the modulation effect
      on SP waves as a function of different thicknesses and different shapes of the
      polymer micro-structures based on the effective refractive index model, where
      imaging properties of the SPs are observed experimentally by detecting the leaky
      radiation intensity of the SPs.

PMID- 19582046
TI  - Eliminate coherence spike in reflection-type pump-probe measurements.
AB  - The coherence spike of femtosecond laser pulses in the reflection-type pump-probe
      measurements has been systematically studied in the semiconductor (100) InP. By
      varying the setup of the pump-probe measuring system, i.e. the polarizations of
      pump and probe pulses, the incident angles of pump and probe beams, and the
      interval of delay time between pump and probe pulses, the dramatic changes in the
      strength of coherence spike could be clear observed. Furthermore, the proposed
      methods to remove the coherence spike from the transient reflectivity curves have
      been demonstrated in the time-domain measurements.

PMID- 19582047
TI  - Light bullets in Bessel optical lattices with spatially modulated nonlinearity.
AB  - We address the stability of light bullets supported by Bessel optical lattices
      with out-of-phase modulation of the linear and nonlinear refractive indices. We
      show that spatial modulation of the nonlinearity significantly modifies the
      shapes and stability domains of the light bullets. The addressed bullets can be
      stable, provided that the peak intensity does not exceed a critical value. We
      show that the width of the stability domain in terms of the propagation constant
      may be controlled by varying the nonlinearity modulation depth. In particular, we
      show that the maximum energy of the stable bullets grows with increasing
      nonlinearity modulation depth.

PMID- 19582048
TI  - Single-shot two-dimensional full-range optical coherence tomography achieved by
      dispersion control.
AB  - We present a full-range Fourier-domain optical coherence tomography (OCT) system
      that is capable of acquiring two-dimensional images of living tissue in a single
      shot. By using line illumination of the sample in combination with a two
      dimensional imaging spectrometer, 1040 depth scans are performed simultaneously
      on a sub-millisecond timescale. Furthermore, we demonstrate an easy and flexible
      real-time single-shot technique for full-range (complex-conjugate cancelled) OCT
      imaging that is compatible with both two-dimensional as well as ultrahigh
      resolution OCT. By implementing a dispersion imbalance between reference and
      sample arms of the interferometer, we eliminate the complex-conjugate signal
      through numerical dispersion compensation, effectively increasing the useful
      depth range by a factor of two. The system allows us to record 6.7 x 3.2 mm
      images at 5 microm depth resolution in 0.2 ms. Data postprocessing requires only
      4 s. We demonstrate the capability of our system by imaging the anterior chamber
      of a mouse eye in vitro, as well as human skin in vivo.

PMID- 19582049
TI  - Surface plasmon effects on two photon luminescence of gold nanorods.
AB  - Gold nanorods emit strong photoluminescence under two photon excitation; the
      efficient two photon lumininescence (TPL) arises from the local field enhancement
      assisted by surface plasmons. The surface plasmon effects on the TPL efficiency
      and spectrum are investigated by measuring the TPL of gold nanorods with various
      aspect ratios. A large TPL efficiency is found when incident light wavelength
      coincides with the longitudinal surface plasmon mode of the gold nanorods.
      However, the emission spectra of nanorods with various aspect ratios look similar
      and exhibit modest surface plasmon features, which implies a major non-radiative
      decay of excited surface plasmons.

PMID- 19582050
TI  - 3D and multispectral imaging for subcutaneous veins detection.
AB  - The first and perhaps most important phase of a surgical procedure is the
      insertion of an intravenous (IV) catheter. Currently, this is performed manually
      by trained personnel. In some visions of future operating rooms, however, this
      process is to be replaced by an automated system. Experiments to determine the
      best NIR wavelengths to optimize vein contrast for physiological differences such
      as skin tone and/or the presence of hair on the arm or wrist surface are
      presented. For illumination our system is composed of a mercury arc lamp coupled
      to a 10nm band-pass spectrometer. A structured lighting system is also coupled to
      our multispectral system in order to provide 3D information of the patient arm
      orientation. Images of each patient arm are captured under every possible
      combinations of illuminants and the optimal combination of wavelengths for a
      given subject to maximize vein contrast using linear discriminant analysis is
      determined.

PMID- 19582051
TI  - High confinement micron-scale silicon nitride high Q ring resonator.
AB  - We demonstrate high confinement, low-loss silicon nitride ring resonators with
      intrinsic quality factor (Q) of 3*10(6) operating in the telecommunication C
      band. We measure the scattering and absorption losses to be below 0.065dB/cm and
      0.055dB/cm, respectively.

PMID- 19582052
TI  - Tomographic scanning imager.
AB  - In tomographic scanning (TOSCA) imaging, light from a scene is focused onto a
      reticle mask using conical scan optics, and collected on a single element
      detector. Alternatively, one or several detectors replace the reticle.
      Tomographic processing techniques are then applied to the one-dimensional signal
      to reproduce a two-dimensional image. The TOSCA technique is presented in detail,
      including its mathematical foundations and some of its limitations. It is shown
      how TOSCA imaging can be used in a multispectral configuration, and compares well
      with more conventional alternatives both in simplicity and performance. Examples
      of image reconstruction using TOSCA techniques are shown.

PMID- 19582053
TI  - A low-absorption x-ray energy filter for small-scale applications.
AB  - We present an experimental and theoretical evaluation of an x-ray energy filter
      based on the chromatic properties of a prism-array lens (PAL). It is intended for
      small-scale applications such as medical imaging. The PAL approximates a Fresnel
      lens and allows for high efficiency compared to filters based on ordinary
      refractive lenses, however at the cost of a lower energy resolution. Geometrical
      optics was found to provide a good approximation for the performance of a
      flawless lens, but a field-propagation model was used for quantitative
      predictions. The model predicted a 0.29 E/E energy resolution and an intensity
      gain of 6.5 for a silicon PAL at 23.5 keV. Measurements with an x-ray tube showed
      good agreement with the model in energy resolution and peak energy, but a blurred
      focal line contributed to a 29% gain reduction. We believe the blurring to be
      caused mainly by lens imperfections, in particular at the periphery of the lens.

PMID- 19582054
TI  - Spatial distributions of the energy and energy flux density of partially coherent
      electromagnetic beams in atmospheric turbulence.
AB  - The formulas of the energy and energy flux density of partially coherent
      electromagnetic beams in atmospheric turbulence are derived by using Maxwell's
      equations. Expressions expressed by elements of electric cross spectral density
      matrixes of the magnetic and the mutual cross spectral density matrix are
      obtained for the partially coherent electromagnetic beams. Taken the partially
      coherent Cosh-Gaussian (ChG) electromagnetic beam as a typical example, the
      spatial distributions of the energy and energy flux density in atmospheric
      turbulence are numerically calculated. It is found that the turbulence shows a
      broadening effect on the spatial distributions of the energy and energy flux
      density. Some interesting results are obtained and explained with regard to their
      physical nature.

PMID- 19582055
TI  - Efficient high-peak-power AlGaInAs eye-safe wavelength disk laser with optical in
      well pumping.
AB  - We have demonstrated an efficient high-peak-power AlGaInAs eye-safe wavelength
      disk laser at 1555 nm. The quantum defect and the thermal load are significantly
      reduced by pumping the quantum well directly. The overall conversion efficiency
      is enhanced over three times compared with the barrier pumping method. With a
      pump peak power of 3.7 kW, an output peak power of 0.52 kW is generated at a
      pulse repetition rate of 20 kHz.

PMID- 19582056
TI  - Phase-sensitive image amplification with elliptical Gaussian pump.
AB  - We numerically analyze phase-sensitive parametric amplification and de
      amplification of a multimode field representing a multi-pixel text image. We
      optimize pumping configuration and demonstrate that approximately 10-dB gain is
      achievable with relatively moderate approximately 10- kW total pump peak power
      available from compact pump sources.

PMID- 19582057
TI  - Liquid crystal Lyot tunable filter with extended free spectral range.
AB  - Extension of the dynamic range of liquid crystal tunable Lyot filter is
      demonstrated by incorporating with it a liquid crystal variable retarder as an
      eliminator for the third and fourth order peaks. The filter is continuously
      tunable in the range 500 nm to 900 nm with a nominal width in the range 50nm
      100nm. Design procedure is described including the exact solution to the LC
      director profile and the suitability for biomedical optical imaging applications.
      Flexibility in the design is proposed by applying different voltages to the
      different liquid crystal retarders thus compensating for small thickness
      deviations from the nominal values and obtaining the high dynamic range.

PMID- 19582058
TI  - Electrophotoluminescence of sol-gel derived ZnO film: effect of electric field on
      near-band-edge photoluminescence.
AB  - The effect of electric field on near-band-edge (NBE) photoluminescence (PL) of a
      sol-gel derived ZnO film has been investigated via a SiO(2)/ZnO/SiOx(x < 2)
      double-barrier structure on Si under different forward biases. A forward current
      voltage curve is characterized by a negative-differential-resistance (NDR)
      region, which follows a normal region. With an increase of forward bias the NBE
      PL of the ZnO film is enhanced in the normal region, but it is attenuated in the
      NDR region. The increase of forward bias also causes the NBE PL of the ZnO film
      to blueshift from approximately 377.6 to approximately 374.9 nm no matter how
      current changes. The mechanism for the effect of bias on the intensity and
      position of NBE PL of the ZnO film is discussed.

PMID- 19582059
TI  - Efficient entanglement distribution over 200 kilometers.
AB  - Here we report the first demonstration of entanglement distribution over a record
      distance of 200 km which is of sufficient fidelity to realize secure
      communication. In contrast to previous entanglement distribution schemes, we use
      detection elements based on practical avalanche photodiodes (APDs) operating in a
      self-differencing mode. These APDs are low-cost, compact and easy to operate
      requiring only electrical cooling to achieve high single photon detection
      efficiency. The self-differencing APDs in combination with a reliable parametric
      down-conversion source demonstrate that entanglement distribution over ultra-long
      distances has become both possible and practical. Consequently the outlook is
      extremely promising for real world entanglement-based communication between
      distantly separated parties.

PMID- 19582060
TI  - Revival of femtosecond laser plasma filaments in air by a nanosecond laser.
AB  - Short lived plasma channels generated through filamentation of femtosecond laser
      pulses in air can be revived after several milliseconds by a delayed nanosecond
      pulse. Electrons initially ionized from oxygen molecules and subsequently
      captured by neutral oxygen molecules provide the long-lived reservoir of low
      affinity allowing this process. A Bessel-like nanosecond-duration laser beam can
      easily detach these weakly bound electrons and multiply them in an avalanche
      process. We have experimentally demonstrated such revivals over a channel length
      of 50 cm by focusing the nanosecond laser with an axicon.

PMID- 19582061
TI  - Scanning from heating: 3D shape estimation of transparent objects from local
      surface heating.
AB  - Today, with quality becoming increasingly important, each product requires three
      dimensional in-line quality control. On the other hand, the 3D reconstruction of
      transparent objects is a very difficult problem in computer vision due to
      transparency and specularity of the surface. This paper proposes a new method,
      called Scanning From Heating (SFH), to determine the surface shape of transparent
      objects using laser surface heating and thermal imaging. Furthermore, the
      application to transparent glass is discussed and results on different surface
      shapes are presented.

PMID- 19582062
TI  - Initiation of laser-induced damage sites in fused silica optical components.
AB  - Significant improvement in the polishing process of fused silica optical
      components has increased their lifetimes at 351 nm. Nevertheless, for large laser
      facilities like the LaserMegaJoule (LMJ), zero defect optical components are not
      yet available. Therefore, a damage mitigation technique has been developed to
      prevent the growth of the laser-initiated damage sites. Because of the difficulty
      to produce mitigated sites with sufficiently large depth, the initial morphology
      of damage to mitigate is a critical issue. The aim of this work is to determine
      laser parameters (pulse duration, fluence) which permit us to initiate damage
      sites in accordance with our mitigation process. Confocal microscopy is used to
      observe damage sites that have sub-surface cracks and consequently to measure
      precisely the diameter and the depth of the area to mitigate.

PMID- 19582063
TI  - Maker fringes in the Terahertz radiation produced by a 2-color laser field in
      air.
AB  - The terahertz radiation produced by a 2-color femtosecond laser scheme strongly
      saturates and develops an oscillatory behavior with increasing power of the
      driving femtosecond laser pulses. This is explained by the formation of a plasma
      channel due to filamentation. Due to dispersion inside the filament and the Gouy
      phase shift, the phase difference between the 800 nm and 400 nm pulses varies
      along this plasma emitter. As a result, the local THz radiations generated along
      the filament interfere destructively or constructively, which manifests itself in
      the form of Maker fringes.

PMID- 19582064
TI  - Structural-configurated magnetic plasmon bands in connected ring chains.
AB  - Magnetic resonance coupling between connected split ring resonators (SRRs) and
      magnetic plasmon (MP) excitations in the connected SRR chains were theoretically
      studied. By changing the connection configuration, two different coupling
      behaviors were observed, and therefore two kinds of MP bands were formed in the
      connected ring chains accordingly. From the extracted dispersion properties of
      MPs, forward and backward characteristics of the guided waves are well exhibited
      corresponding to the homo- and hetero-connected chains. Notably, thanks to the
      conductive coupling the revealed MP waves both have wide bandwidth even starting
      from the zero frequency. These results are suggested to provide instructions to
      build new kinds of subwavelength waveguides.

PMID- 19582065
TI  - Surface plasmon-enhanced energy transfer in an organic light-emitting device
      structure.
AB  - We present a surface plasmon-mediated energy transfer based on an organic light
      emitting device structure. In order to localize surface plasmons, silver nano
      clusters were deposited thermally close to the cathode with a 1-nm-thick LiF
      spacer. It was shown that the surface plasmon formed on the silver nano cluster
      provides a strong donor decay channel and increases the donor-acceptor dipolar
      interaction. Thus, photoluminescence results displayed 3.5-fold enhanced acceptor
      emission intensity, compared with those of sample which has no Ag nano cluster.

PMID- 19582066
TI  - Macroscopic entanglement and violation of Bell's inequalities between two
      spatially separated quantum dots in a planar photonic crystal system.
AB  - We present and apply a medium-dependent quantum optics formalism for describing
      the exciton dynamics of two spatially-separated quantum dots on-chip, in the
      regime of coupled-cavity quantum electrodynamics. With each dot placed in a
      spatially-separated cavity and coupled through a periodic waveguide channel, the
      quantum dot excitons behave as a composite entangled pair, exhibiting pronounced
      entanglement over distances of 300 microm and more. The computed light spectra
      above the two cavities show clear signatures of pronounced photon coupling
      including increased vacuum Rabi splitting and cavity-induced transmission and
      absorption. The macroscopic entanglement is confirmed by investigating the Bell
      inequality, which is shown to be violated for hundreds of picoseconds.

PMID- 19582067
TI  - Quasi-distributed long-gauge fiber optic sensor system.
AB  - This paper presents a quasi-distributed, long-gauge, sensor system for
      measurement optical path length variation. This system can be directly applied to
      long gauge strain and/or temperature sensing. The proposed sensor system is
      comprised of sensing fiber, which is divided into the sensor's segments separated
      by semi reflective mirrors made out of standard optical connectors. Short
      duration radio-frequency modulated optical bursts are launched into the sensing
      fiber and phase differences among individual reflected bursts are measured to
      determine the optical path-length variations among neighboring mirrors. Twenty
      sensing fiber segments were successfully addressed by a single-signal processor,
      while relying on standard telecommunication PIN diode, and a Fabry Perot laser
      diode. The resolution of a fiber-length variation better than 5 microm was
      demonstrated in practice. Since the long sections of fiber can be employed for
      constructing individual sensors within the sensor's array, a microstrain
      resolution can be achieved in practice. The drift of the sensor's system can be
      predominantly attributed to the temperature sensitivity of the electronic
      components, which proved to be below 20 microm/ degrees C. The entire system
      relies on simple and widely-used components that are low-cost.

PMID- 19582068
TI  - Polarization independent beam fanning using a multi-domain liquid crystal cell.
AB  - Polarization independent beam fanning using a multi-domain liquid crystal (LC)
      cell is demonstrated experimentally. In the neighboring domains, the LC directors
      are aligned in orthogonal directions. To prove concepts, two hybrid-aligned LC
      cells with four and six domains were fabricated. Applying a voltage across the LC
      layer will change the phase difference between the neighboring domains. When the
      phase difference is 2mpi (m is an integer), the LC cell will not disturb the
      incident beam. However, if the phase shift is (2m + 1)pi, the outgoing beam will
      fan out into several beams; the number of fanout beams is equal to the domain
      number.

PMID- 19582069
TI  - LD pumped Yb:LuAG mode-locked laser with 7.63ps duration.
AB  - Diode-pumped Yb:LuAG laser has been passively mode locked with a SESAM for the
      first time to the authors' knowledge. The pulses as short as 7.63ps were
      generated, without negative dispersion elements. The output power achieved 610mW
      at pump of 11.2W with repetition rate of 86MHz. The continuous-wave operation and
      wavelength tuning pumped at 940nm were also examined, and its tuning can cover
      the range of 1033nm-1079nm.

PMID- 19582070
TI  - Broadband and high power terahertz pulse generation beyond excitation bandwidth
      limitation via chi2 cascaded processes in LiNbO3.
AB  - We proposed a novel THz generation technique beyond the limitation of the input
      optical pulse width, based on phase modulation via cascaded chi((2)) process.
      When intense THz electric field generated by optical rectification lies in
      electro-optic (EO) crystal, emitted THz field gives phase modulation to the
      optical excitation pulse. The phase modulation causes excitation pulse narrowing
      and consequently gives rise to the enhancement of conversion efficiency and THz
      wave bandwidth broadening. We experimentally realize this generation technique
      with high chi((2)) EO crystal LiNbO(3) and with subpicosecond pulse from Yb-doped
      fiber laser. It opens new concept of THz technologies.

PMID- 19582071
TI  - Geometrically distributed one-dimensional photonic crystals for light-reflection
      in all angles.
AB  - We demonstrate that a series of one-dimensional photonic crystals made of any
      dielectric materials, with the periods are distributed in a geometrical
      progression of a common ratio, r < rc (theta,P), where rc is a structural
      parameter that depends on the angle of incidence, theta, and polarization, P, is
      capable of blocking light of any spectral range. If an omni-directional
      reflection is desired for all polarizations and for all incident angles smaller
      than thetao, then r < rc (theta(o),p), where p is the polarization with the
      electric field parallel to the plane of incidence. We present simple and formula
      like expressions for rc, width of the bandgap, and minimum number of photonic
      crystals to achieve a perfect light reflection.

PMID- 19582072
TI  - Engineered nonlinear photonic quasicrystals for multi-frequency terahertz
      manipulation.
AB  - The interactions between electromagnetic wave and photonic quasicrystals are
      investigated. A terahertz (THz) source with multi-frequency modes in an optical
      LiTaO(3) superlattice produced by quasiperiodic (Fibonacci) domain-inverted
      ferroelectric material is demonstrated experimentally. Using the canonical pump
      probe experimental technique, THz radiations in both forward and backward
      propagations are in-situ detected simultaneously. Four pronounced THz frequencies
      at 1.18, 0.78, 0.59 and 0.37 THz in Fourier transform spectrum are observed. The
      physical properties of THz waves inside quasiperiodic superlattice are discussed.

PMID- 19582073
TI  - A full vectorial model for pulse propagation in emerging waveguides with
      subwavelength structures part II: Stimulated Raman Scattering.
AB  - The significance of full vectorial pulse propagation through emerging waveguides
      has not been investigated. Here we report the development of a generalised
      vectorial model of nonlinear pulse propagation due to the effects of Stimulated
      Raman Scattering (SRS) in optical waveguides. Unlike standard models, this model
      does not use the weak guidance approximation, and thus accurately models the
      modal Raman gain of optical waveguides in the strong guidance regime. Here we
      develop a vectorial-based nonlinear Schrodinger Eq. (VNSE) to demonstrate how the
      standard model fails in certain regimes, with up to factors of 2.5 enhancement in
      Raman gain between the VNSE and the standard model. Using the VNSE we are able to
      explore opportunities for tailoring of the modal Raman gain spectrum to achieve
      effects such as gain flattening through design of the optical fiber.

PMID- 19582074
TI  - Analytical theory of wave propagation through stacked fishnet metamaterials.
AB  - This work analyzes the electromagnetic wave propagation through periodically
      stacked fishnets from zero frequency to the first Wood's anomaly. It is shown
      that, apart from Fabry-Perot resonances, these structures support two
      transmission bands that can be backward under the appropriate conditions. The
      first band starts at Wood's anomaly and is closely related to the well-known
      phenomena of extraordinary transmission through a single fishnet. The second band
      is related to the resonances of the fishnet holes. In both cases, the in-plane
      periodicity of the fishnet cannot be made electrically small, which prevents any
      attempt of homogenization of the structure along the fishnet planes. However,
      along the normal direction, even with very small periodicity transmission is
      still possible. An homogenization procedure can then be applied along this
      direction, thus making that the structure can behave as a backward-wave
      transmission line for such transmission bands. Closed-form design formulas will
      be provided by the analytical formulation here presented. These formulas have
      been carefully validated by intensive numerical computations.

PMID- 19582075
TI  - Scene-based spectral calibration assessment of high spectral resolution imaging
      spectrometers.
AB  - An accurate knowledge of the spectral calibration of imaging spectrometers is
      required for optimum data processing and interpretation. The scene-based spectral
      characterization of imaging spectrometers is frequently necessary to update or
      replace the pre-flight laboratory-based spectral characterization supplied by the
      data provider. An automatic method for the estimation of spectral calibration
      parameters (channel position and bandwidth) at atmospheric absorption regions
      from high spectral resolution imaging spectrometers (spectral sampling interval
      below 5 nm) is presented in this contribution. The method has been tested on two
      commercial instruments with spectral sampling intervals below 2.5 nm. Optical
      aberrations such as smile, spectrometer shift and rotation and degradation of
      channel bandwidth have been detected and are discussed in terms of potential
      error sources at the instrument level.

PMID- 19582077
TI  - Simplified model for periodic nanoantennae: linear model and inverse design.
AB  - We determine and use a minimal set of numerical simulations to create a
      simplified model for the spectral response of nanoantennae with respect to their
      geometric and modeling parameters. The simplified model is then used to rapidly
      obtain best-fit modeling parameters to match experimental results, accurately
      predict the spectral response for various geometries, and inversely design
      antennae to have a desired performance. This method is structure and model
      independent, and is applied here to both nanoantenna pair arrays and strips
      modeled using a 3D finite-element method and 2D spatial harmonic analysis,
      respectively. Typical numerical simulations may need hours per model, whereas
      this method, after the initial time to obtain a baseline set of simulations,
      requires only seconds to analyze and generate spectra for new geometries.

PMID- 19582078
TI  - Influence of partial coherence on analyzer-based imaging with asymmetric Bragg
      reflection.
AB  - Image magnification via twofold asymmetric Bragg reflection (a setup called the
      "Bragg Magnifier") is a recently established technique allowing to achieve both
      sub-micrometer spatial resolution and phase contrast in X-ray imaging. The
      present article extends a previously developed theoretical formalism to account
      for partially coherent illumination. At a typical synchrotron setup polychromatic
      illumination is identified as the main influence of partial coherence and the
      implications on imaging characteristics are analyzed by numerical simulations. We
      show that contrast decreases by about 50% when compared to the monochromatic
      case, while sub-micrometer spatial resolution is preserved. The theoretical
      formalism is experimentally verified by correctly describing the dispersive
      interaction of the two orthogonal magnifier crystals, an effect that has to be
      taken into account for precise data evaluation.

PMID- 19582079
TI  - Atmospheric turbulence correction using digital holographic detection:
      experimental results.
AB  - The performance of long distance imaging systems is typically degraded by phase
      errors imparted by atmospheric turbulence. In this paper we apply coherent
      imaging methods to determine, and remove, these phase errors by digitally
      processing coherent recordings of the image data. In this manner we are able to
      remove the effects of atmospheric turbulence without needing a conventional
      adaptive optical system. Digital holographic detection is used to record the
      coherent, complex-valued, optical field for a series of atmospheric and object
      realizations. Correction of atmospheric phase errors is then based on maximizing
      an image sharpness metric to determine the aberrations present and correct the
      underlying image. Experimental results that demonstrate image recovery in the
      presence of turbulence are presented. Results obtained with severe turbulence
      that gives rise to anisoplanatism are also presented.

PMID- 19582080
TI  - The effect of a small heat source on PSF stability for high-contrast imaging.
AB  - High-contrast adaptive optics systems, such as those needed to image extrasolar
      planets, are known to require excellent wavefront control and diffraction
      suppression. The Laboratory for Adaptive Optics at UC Santa Cruz is investigating
      limits to high-contrast imaging in support of the Gemini Planet Imager (GPI). In
      this paper we examine the effect of heat sources in the testbed on point-spread
      function (PSF) stability. Introducing a heat source primarily introduces image
      motion. The GPI error budget requires image motion to be less than 0.1 lambda /D.
      Systematic motion of the PSF core is typically 0.01 lambda /D rms and with a 20
      watt heat source introduced near the pupil plane image motion is increased to
      0.02 lambda /D rms. Therefore, even a heat source as large as 20 watts near the
      pupil plane causes errors below the GPI requirement, but the combination of the
      heat source and additional air turbulence on the system introduced by changes to
      the enclosure or the fan of other components can produce significantly more
      motion. Heat also can affect the speckle pattern in the high-contrast region, but
      in the final instrument other sources of error should be more significant.

PMID- 19582081
TI  - Reconstruction of in-vivo optical properties for human prostate using
      interstitial diffuse optical tomography.
AB  - A CW interstitial diffuse optical tomography has been developed to characterize
      the in-vivo optical properties of prostate gland during photodynamic therapy. The
      spatial distributions of light fluence rate can be described by the diffusion
      equation. Optical properties of the prostate are reconstructed by solving the
      inverse problem with an adjoint method. The 3D reconstructed in-vivo optical
      properties for a human prostate is illustrated and compared with the results
      generated by a well-established point-by-point method. Moreover, the calculated
      fluence rate using the reconstructed optical properties matches the measured
      data.

PMID- 19582082
TI  - Improvement of matrix condition of Hybrid, space variant optics by the means of
      parallel optics design.
AB  - The problem of image restoration of space variant blur is common and important.
      One of the most useful descriptions of this problem is in its algebraic form
      I=H*O, where O is the object represented as a column vector, I is the blur image
      represented as a column vector and H is the PSF matrix that represents the
      optical system. When inverting the problem to restore the geometric object from
      the blurred image and the known system matrix, restoration is limited in speed
      and quality by the system condition. Current optical design methods focus on
      image quality, therefore if additional image processing is needed the matrix
      condition is taken "as is". In this paper we would like to present a new optical
      approach which aims to improve the system condition by proper optical design. In
      this new method we use Singular Value Decomposition (SVD) to define the weak
      parts of the matrix condition. We design a second optical system based on those
      weak SVD parts and then we add the second system parallel to the first one. The
      original and second systems together work as an improved parallel optics system.
      Following that, we present a method for designing such a "parallel filter" for
      systems with a spread SVD pattern. Finally we present a study case in which by
      using our new method we improve a space variant image system with an initial
      condition number of 8.76e4, down to a condition number of 2.29e3. We use matrix
      inversion to simulate image restoration. Results show that the new parallel
      optics immunity to Additive White Gaussian Noise (AWGN) is much better then that
      of the original simple lens. Comparing the original and the parallel optics
      systems, the parallel optics system crosses the MSEIF=0 [db] limit in SNR value
      which is more than 50db lower then the SNR value in the case of the original
      simple lens. The new parallel optics system performance is also compared to
      another method based on the MTF approach.

PMID- 19582083
TI  - Origin of the anomalous temperature evolution of photoluminescence peak energy in
      degenerate InN nanocolumns.
AB  - Photoluminescence (PL) behaviour in InN nanocolumns reveal decreasing, increasing
      and near invariant peak energies (E(PL)) as a function of temperature. Samples,
      having E(PL)~0.730 eV at 20 K, showed temperature invariance of E(PL). Samples
      possessing E(PL) on the lower and higher energy side of 0.730 eV demonstrate a
      normal redshift and anomalous blueshift, respectively, with increasing
      temperature. This temperature evolution can be effectively explained on the basis
      of a competition between a conventional red shift from lattice dilation, dominant
      for low carrier density sample, on one hand, and a blue shift of the electron and
      hole quasi Fermi-level separation, dominant for high carrier density samples, on
      the other.

PMID- 19582084
TI  - Breathing solitons in nematic liquid crystals.
AB  - Dynamical and steady-state behavior of beams propagating in nematic liquid
      crystals (NLCs) is analyzed. A well-known model for the beam propagation and the
      director reorientation angle in a NLC cell is treated numerically in space and
      time. The formation of steady-state soliton breathers in a threshold region of
      beam intensities is displayed. Below the region the beams diffract, above the
      region spatiotemporal instabilities develop, as the input intensity and the
      material parameters are varied. Curiously, the only kind of solitons we could
      demonstrate in our numerical studies was the breathers. Despite repeated efforts,
      we could not find the solitons with a steady profile propagating in the NLC model
      at hand.

PMID- 19582085
TI  - Grating induced transparency (GIT) and the dark mode in optical waveguides.
AB  - We propose and describe a new class of optical modes consisting of superposition
      of three waveguide modes which can be supported by a few-mode waveguide spatially
      modulated by two co-spatial gratings. These supermodes bear a close, but not
      exact, formal analogy to the three-level quantum states involved in EIT and its
      attendant slow light propagation characteristics. Of particular interest is the
      supermode which we call the dark mode in which, in analogy with the dark state of
      EIT, one of the three uncoupled waveguide modes is not excited. This mode has
      unique dispersion characteristics that translate into a slow light propagation
      which possesses high bandwidth-delay product and can form the basis for a new
      generation of optical resonators and lasers.

PMID- 19582086
TI  - Femtosecond laser written optofluidic sensor: Bragg Grating Waveguide evanescent
      probing of microfluidic channel.
AB  - Microfluidic channels and Bragg Grating Waveguides (BGWs) were simultaneously
      fabricated inside fused silica glass by means of femtosecond laser exposure
      followed by chemical etching. Evanescent field penetration of the waveguide mode
      into the parallel microfluidic channel induced Bragg resonant wavelength shifts
      to enable refractive index characterization of the fluidic medium in the 1 to
      1.452 range. Laser exposure was optimized to fabricate devices with optically
      smooth channel walls and narrow Bragg resonances for high sensing response at
      1560 nm wavelength. Reference gratings were also employed in the optical circuit
      for temperature and strain compensation. These devices open new directions for
      optical sensing in three-dimensional optofluidic and reactor microsystems.

PMID- 19582087
TI  - Regular and anomalous extraordinary optical transmission at the THz-gap.
AB  - In this paper Anomalous Extraordinary Transmission (ET) is reported for s
      polarization of low loss doubly periodic subwavelength hole arrays patterned on
      polypropylene (PP) substrates by conventional contact photolithography at the so
      called THz-gap (1-10 THz). The unexpected enhanced transmittance for s
      polarization (i.e. without spoof plasmons) was previously numerically
      demonstrated in subwavelength slits arrays. However, subsequently no experimental
      work has been devoted to this unexpected Extraordinary Transmission neither in
      subwavelength slits nor in subwavelength holes. Here, numerical study and
      experimental results of the Anomalous ET and the symmetric and antisymmetric
      transmittance modes associated with the already well-known p-polarization ET are
      shown alongside a systematically analysis of the frequency peaks as a function of
      hole size for both incident polarizations.

PMID- 19582088
TI  - Design and fabrication of poly(dimethylsiloxane) single-mode rib waveguide.
AB  - We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS)
      single-mode rib waveguides. PDMS was chosen specifically for the core and
      cladding. Combined with the soft lithography fabrication techniques, it enables
      an easy integration of microoptical components for lab-on-a-chip systems. The
      refractive index contrast, of 0.07% between the core and cladding for single-mode
      propagation was achieved by modifying the properties of the same base material.
      Alternatively, a higher refractive index contrast, of 1.18% was shown by using
      PDMS materials from two different manufacturers. The fabricated rib waveguides
      were characterized for mode profile characteristics and confirmed the excitation
      of the fundamental mode of the waveguide. The propagation loss of the single-mode
      rib waveguide was characterized using the cutback measurement method at a
      wavelength of 635 nm and found to be 0.48 dB/cm for of 0.07% and 0.20 dB/cm for
      of 1.18%. Y-branch splitter of PDMS single-mode rib waveguide was further
      demonstrated.

PMID- 19582089
TI  - Small-scale effects of underwater bubble clouds on ocean reflectance: 3-D
      modeling results.
AB  - We examined the effect of individual bubble clouds on remote-sensing reflectance
      of the ocean with a 3-D Monte Carlo model of radiative transfer. The
      concentrations and size distribution of bubbles were defined based on acoustical
      measurements of bubbles in the surface ocean. The light scattering properties of
      bubbles for various void fractions were calculated using Mie scattering theory.
      We show how the spatial pattern, magnitude, and spectral behavior of remote
      sensing reflectance produced by modeled bubble clouds change due to variations in
      their geometric and optical properties as well as the background optical
      properties of the ambient water. We also determined that for realistic sizes of
      bubble clouds, a plane-parallel horizontally homogeneous geometry (1-D radiative
      transfer model) is inadequate for modeling water-leaving radiance above the
      cloud.

PMID- 19582090
TI  - The geodesic form of light-ray trace in the inhomogeneous media.
AB  - The canonical equations of the optical cloaking proposed by Shurig, Pendry and
      Smith has been proved to be equivalent to the geodesic in a 3-dimensional curved
      space. Carrying out the argument we extend to the 4-dimensional Riemannian space
      where the extra time item appears as the potential term in the canonical
      equations. The physical meaning of the results is interpreted.

PMID- 19582091
TI  - Investigation on the effect of EDFA location in ring cavity Brillouin-Erbium
      fiber laser.
AB  - We have investigated the characteristics of Brillouin-Erbium fiber laser (BEFL)
      with variation of Erbium-doped fiber amplifier (EDFA) locations in a ring cavity
      configuration. Three possible locations of the EDFA in the laser cavity have been
      studied. The experimental results show that the location of EDFA plays vital role
      in determining the output power and the tuning range. Besides the Erbium gain,
      Brillouin gain also contributes to the performance of the BEFL. By placing the
      EDFA next to the Brillouin gain medium (dispersion compensating fiber), the
      Brillouin pump signal is amplified thereby generating higher intensities of
      Brillouin Stokes line. This efficient process suppresses the free running self
      lasing cavity modes from oscillating in cavity as a result of higher Stokes laser
      power and thus provide a wider tuning range. At the injected Brillouin pump power
      of 1.6 mW and the maximum 1480 nm pump power of 135 mW, the maximum Stokes laser
      power of 25.1 mW was measured and a tuning range of 50 nm without any self-lasing
      cavity modes was obtained.

PMID- 19582092
TI  - Rains of solitons in a fiber laser.
AB  - We report a novel and intriguing nonlinear dynamics observed in a fiber laser
      cavity, in which soliton pulses are created from an extended noisy background and
      drift until they reach a condensed phase comprising several tens of aggregated
      solitons. This soliton flow can be adjusted with manual cavity tuning, and can
      even be triggered by the injection of an external low-power cw laser.

PMID- 19582093
TI  - Extremely large mode area optical fibers formed by thermal stress.
AB  - We report a strictly single-mode optical fiber with a record core diameter of 84
      microm and an effective mode area of approximately 3600 microm(2) at 1 microm. We
      also demonstrate fundamental mode operation in an optical fiber with a record
      core diameter of 252 microm and a measured mode field diameter (MFD) of 149
      microm at 1.03 microm, i.e. an effective mode area (Aeff) of approximately 17,400
      microm(2) at 1.03 microm, an Aeff of 31,600 microm(2) at 1.5 microm. All these
      fibers have near parabolic index profiles with a peak refractive index difference
      DeltaN approximately approximately 6 x 10(-5), i.e. a record low numerical
      aperture (NA) of approximately 0.013 in an optical fiber. This low refractive
      index difference was achieved by frozen-in thermal stress as a result of two
      different types of glass in the fibers. When the fundamental mode was excited in
      the 252 microm core fiber using a 1.03 microm ASE source, the output beam was
      measured to have M2x = 1.04 and M2y = 1.18.

PMID- 19582094
TI  - Optical nanoheater based on the Yb3+-Er3+ co-doped nanoparticles.
AB  - Yb(3+)-Er(3+) co-doped fluoride nanoparticles have been prepared. When pumped by
      975 nm laser diode into absorption band of Yb(3+), the laser-induced temperature
      rise up to 800 degrees C has been detected in the nanoparticles by measuring the
      ratio of the intensities of the thermalised up-conversion luminescence bands
      (2)H(11/2)-->(4)I(15/2) and (4)S(3/2)-->(4)I(15/2) of Er(3+). These results show
      that a controlled optical heating of the nanoparticles and their surrounding nano
      volumes can be realised, while the location and temperature rise of the
      nanoparticles and heated nano-volumes can be detected distantly by means of
      luminescence.

PMID- 19582095
TI  - Photostatistics reconstruction via loop detector signatures.
AB  - Photon-number resolving detectors are a fundamental building-block of optical
      quantum information processing protocols. A loop detector, combined with
      appropriate statistical processing, can be used to convert a binary on/off photon
      counter into a photon-number-resolving detector. Here we describe the idea of a
      signature of photon-counts, which may be used to more robustly reconstruct the
      photon number distribution of a quantum state. The methodology is applied
      experimentally in a 9-port loop detector operating at a telecommunications
      wavelength and compared directly to the approach whereby only the number of
      photon-counts is used to reconstruct the input distribution. The signature
      approach is shown to be more robust against calibration errors, exhibit reduced
      statistical uncertainty, and reduced reliance on a-priori assumptions about the
      input state.

PMID- 19582097
TI  - Numerical simulations of a surface plasmonic waveguide with three circular air
      cores.
AB  - In this paper, a kind of surface plasmonic waveguide (SPW) with three circular
      air cores is presented. Based on the finite-difference frequency-domain (FDFD)
      method, dependence of the distribution of energy flux density, effective index,
      propagation length and mode area of the fundamental mode on the geometrical
      parameters and the working wavelengths is analyzed firstly. Then, comparison with
      the SPW which was proposed in our previous work has been carried out. Results
      show that this kind of three cores structure has better propagation properties
      than the double cores structure. To investigate the relative advantages of this
      kind of SPW over other previous reported SPWs, comparison with the SPW with a
      single wedge has been carried out. Results show that this kind of SPW has shorter
      propagation length and larger mode area. Finally, the possibility to overcome the
      large propagation loss by using a gain medium as core material is investigated.
      Since the propagation properties can be adjusted by the geometrical and
      electromagnetic parameters, this kind of surface plasmonic waveguide can be
      applied to the field of photonic components in the integrated optical circuits
      and sensors.

PMID- 19582096
TI  - Optical characterization of adaptive fluidic silicone-membrane lenses.
AB  - We present an extended optical characterization of an adaptive microfluidic
      silicone-membrane lens at a wavelength of 633 nm, respectively 660 nm. Two
      different membrane variations; one with a homogeneous membrane thickness, and one
      with a shaped cross section, have been realized. This paper includes the
      theoretical predictions of the optical performance via FEM simulation and ray
      tracing, and a subsequent orientation dependent experimental analysis of the lens
      quality which is measured with an MTF setup and a Mach-Zehnder interferometer.
      The influence of the fabrication process on the optical performance is also
      characterized by the membrane deformation in the non-deflected state. The lens
      with the homogeneous membrane of 5 mm in diameter and an aperture of 2.5 mm
      indicates an almost orientation independent image quality of 117 linepairs/mm at
      a contrast of 50%. The shaped membrane lenses show a minimum wave front error of
      WFE(RMS) = 24 nm, and the lenses with a planar membrane of WFE(RMS) = 31 nm at an
      aperture of 2.125 mm.

PMID- 19582098
TI  - Three-dimensional holographic imaging of living tissue using a highly sensitive
      photorefractive polymer device.
AB  - Photorefractive materials are dynamic holographic storage media that are highly
      sensitive to coherent light fields and relatively insensitive to a uniform light
      background. This can be exploited to effectively separate ballistic light from
      multiply-scattered light when imaging through turbid media. We developed a highly
      sensitive photorefractive polymer composite and incorporated it into a
      holographic optical coherence imaging system. This approach combines the
      advantages of coherence-domain imaging with the benefits of holography to form a
      high-speed wide-field imaging technique. By using coherence-gated holography,
      image-bearing ballistic light can be captured in real-time without computed
      tomography. We analyzed the implications of Fourier-domain and image-domain
      holography on the field of view and image resolution for a transmission recording
      geometry, and demonstrate holographic depth-resolved imaging of tumor spheroids
      with 12 microm axial and 10 microm lateral resolution, achieving a data
      acquisition speed of 8 x 10(5) voxels/s.

PMID- 19582099
TI  - Acceleration of electrons by a tightly focused intense laser beam.
AB  - The recent proposal to use Weinger transformation field (WTF) [Opt. Express 17,
      4959-4969 (2009)] for describing tightly focused laser beams is investigated here
      in detail. In order to validate the accuracy of WTF, we derive the numerical
      field (NF) from the plane wave spectrum method. WTF is compared with NF and Lax
      series field (LSF). Results show that LSF is accurate close to the beam axis and
      divergent far from the beam axis, and WTF is always accurate. Moreover, electron
      dynamics in a tightly focused intense laser beam are simulated by LSF, WTF and
      NF, respectively. The results obtained by WTF are shown to be accurate.

PMID- 19582100
TI  - Photoluminescence eigenmodes in a single ZnO nanobelt covering the ultraviolet
      and visible band.
AB  - The photoluminescence properties of a ZnO nanobelt are investigated. Both the
      band-edge emission and the green-yellow emission bands have a series of
      eigenmodes. The theoretical results demonstrate that in the band-edge emission
      region the photoluminescence modes are determined by the polariton modes. In the
      green-yellow band there is no coupling between the photons and excitons and the
      photoluminescence modes are determined by the transverse Fabry-Perot modes. The
      photoluminescence spectra at different spots confirm that the Fabry-Perot modes
      are determined by the transverse size. Furthermore, the fitting results show in
      the waveband in the ultraviolet and visible band the quality-factor Q of the
      cavity is decreased from 280 to 70 with the increase of the wavelength.

PMID- 19582101
TI  - Photonic bandgap fibers with resonant structures for tailoring the dispersion.
AB  - Numerical simulations on different kinds of realistic photonic bandgap fibers
      exhibiting reversed dispersion slope for the propagating fundamental mode are
      reported. We show that reversed or flat dispersion functions in a wide wavelength
      range using hollow-core, air-silica photonic bandgap fibers and solid core Bragg
      fibers with step-index profile can be obtained by introducing resonant structures
      in the fiber cladding. We evaluate the dispersion and confinement loss profiles
      of these fibers from the Helmholtz eigenvalue equation and the calculated fiber
      properties are used to investigate the propagation of chirped femtosecond pulses
      through serially connected hollow core fiber compressors.

PMID- 19582102
TI  - Adjusting resonant wavelengths and spectral shapes of ring resonators using a
      cladding SiN layer or KOH solution.
AB  - It is shown that the resonant frequencies and the transmission spectra of ring
      resonators can be adjusted by depositing or etching the cladding nitride layer on
      the ring waveguide without introducing an extra loss or extra variations of
      channel spacing. The cladding nitride layer increases the minimum width of the
      gap in the coupling region to larger than 150nm which makes it possible to
      consider photolithography instead of E-beam lithography for the typical design
      rule of ring filters. KOH silicon etching can also adjust not only the resonance
      frequencies but also coupling coefficients with a small sacrifice of guiding
      loss.

PMID- 19582103
TI  - High-efficiency Q-switched dual-wavelength emission at 1176 and 559 nm with
      intracavity Raman and sum-frequency generation.
AB  - An efficient Q-switched dual-wavelength laser with self-frequency Raman
      conversion in composite Nd:YVO(4) and intracavity sum-frequency generation in BBO
      is reported. With an input pump power of 17.5 W, average power of 0.53 W at the
      first-Stokes 1176 nm and average power of 1.67 W at the sum-frequency mixed 559
      nm are simultaneously generated at a pulse repetition rate of 100 kHz,
      corresponding to a total conversion efficiency of 12.5%.

PMID- 19582104
TI  - Theory of energy evolution in laser resonators with saturated gain and non
      saturated loss.
AB  - Theory of the energy evolution in laser resonators with saturated gain and non
      saturated loss is revisited. An explicit analytical expression for the output
      energy/average power in terms of the gain saturation energy, cavity loss and
      small signal gain parameters is derived for a ring cavity configuration.

PMID- 19582105
TI  - Astigmatic phase retrieval: an experimental demonstration.
AB  - We present the first experimental demonstration of the astigmatic phase retrieval
      technique, in which the diffracted wavefield is distorted by cylindrical
      curvature in two orthogonal directions. A charge-one vortex, a charge-two vortex,
      and a simple test image are all correctly reconstructed.

PMID- 19582106
TI  - Selective excitation of whispering gallery modes in a novel bottle
      microresonator.
AB  - Selective excitation of spheroidal whispering gallery modes and bottle modes in a
      robust bottle microresonator fabricated straightforwardly from a short section of
      optical fiber is demonstrated. Characteristic resonance spectra of long-cavity
      bottle modes were obtained by using a tapered fiber to excite evanescently bottle
      microresonator at different points along its axis. Compared to bare-fiber
      cylindrical resonators, the bottle microresonator results in a 35x increase of
      the observed Q factor.

PMID- 19582107
TI  - Fabrication of liquid crystal polymer axial waveplates for UV-IR wavelengths.
AB  - We show the opportunity of fabricating axially symmetric waveplates fine tuned to
      a desired wavelength. High quality waveplates are obtained using liquid crystal
      polymer layers on photoaligning substrates extending their functional range from
      UV to IR wavelengths. We characterize the effect of the waveplate on laser beams
      showing formation of a doughnut beam with over 240 times attenuation of intensity
      on the axis. We pay attention that the power density is strongly reduced on the
      doughnut ring as well and use this opportunity for taking charge coupled devices
      (CCDs) out of a deep saturation regime. Strong deformation of the beam profile is
      observed when the vortex axis is shifted towards the periferies of the beam. We
      demonstrate feasibility of using this phenomenon for shaping the profile of light
      beams with a set of waveplates.

PMID- 19582108
TI  - Influence of energy-transfer-upconversion on threshold pump power in quasi-three
      level solid-state lasers.
AB  - A simple analytical expression for threshold pump power in an end-pumped quasi
      three-level solid-state laser, which takes into account the influence of energy
      transfer-upconversion (ETU), is derived. This expression indicates that threshold
      pump power can be increased dramatically by ETU, especially in low gain lasers
      and lasers with pronounced three-level character due to the need for high
      excitation densities in the upper manifold to reach threshold. The analysis has
      been applied to an Er:YAG laser operating at 1645 nm in-band pumped by an Er,Yb
      fiber laser at 1532 nm. Predicted values for threshold pump power as a function
      of erbium doping concentration are in very good agreement with measured values.
      The results indicate that very low erbium doping levels (approximately 0.25 at.%
      or less) are required to avoid degradation in performance due to ETU even under
      continuous-wave lasing conditions in Er:YAG.

PMID- 19582109
TI  - Nanoparticle plasmonics for 2D-photovoltaics: mechanisms, optimization, and
      limits.
AB  - Plasmonic nanostructures placed within or near photovoltaic (PV) layers are of
      high current interest for improving thin film solar cells. We demonstrate, by
      electrodynamics calculations, the feasibility of a new class of essentially two
      dimensional (2D) solar cells based on the very large optical cross sections of
      plasmonic nanoparticles. Conditions for inducing absorption in extremely thin PV
      layers via plasmon near-fields, are optimized in 2D-arrays of (i) core-shell
      particles, and (ii) plasmonic particles on planar layers. At the plasmon
      resonance, a pronounced optimum is found for the extinction coefficient of the PV
      material. We also characterize the influence of the dielectric environment, PV
      layer thickness and nanoparticle shape, size and spatial distribution. The
      response of the system is close to that of a 2D effective medium layer, and
      subject to a 50% absorption limit when the dielectric environment around the 2D
      layer is symmetric. In this case, a plasmon induced absorption of about 40% is
      demonstrated in PV layers as thin as 10 nm, using silver nanoparticle arrays of
      only 1 nm effective thickness. In an asymmetric environment, the useful
      absorption may be increased significantly for the same layer thicknesses. These
      new types of essentially 2D solar cells are concluded to have a large potential
      for reducing solar electricity costs.

PMID- 19582110
TI  - 1.56-micros continuously tunable parametric delay line for a 40-Gb/s signal.
AB  - Experimental demonstration of an all-fiber, all-optical continuously tunable
      delay line is reported. The 1.56-micros delay with a record 62,400 time-delay bit
      rate product was characterized for a 40-Gbps data channel. The result was enabled
      by parametric dispersion compensation with cascaded triple-conversion in highly
      nonlinear fiber capable of continuous tuning over 39.5 nm.

PMID- 19582111
TI  - Acousto-optic tunable second harmonic generation in periodically poled LiNbO3.
AB  - Acousto-optic (AO) tunable second harmonic generation (SHG) was proposed in
      periodically poled lithium niobate (PPLN). The acoustic wave could either be
      induced from an external transducer or self-generated in PPLN driving with a
      cross-field radio frequency field. The reciprocal vector of PPLN compensates the
      SHG wave-vector mismatch when quasi-phase- matching (QPM) condition is satisfied,
      while phonons with suitable frequencies may affect it by scattering photons to
      different polarization state. The QPM SHG and AO polarization rotation are
      coupled together. Second harmonic waves' intensities, polarization states and
      even phases thus could be manipulated instantly through AO interaction.

PMID- 19582112
TI  - Er-doped fiber frequency comb with mHz relative linewidth.
AB  - A low-noise fiber frequency comb is demonstrated to improve the frequency
      accuracy and linewidth by suppressing the phase noise caused by the nonlinear
      self-phase modulation as well as the amplified spontaneous emission within the Er
      doped fiber amplifier. The linewidth of the carrier-envelop- offset signal
      measures less than 1.9 mHz and the frequency stability well follows the reference
      Rb clock. This achievement will facilitate the use of the fiber frequency comb
      for industrial applications to precision near-infrared spectroscopy, frequency
      calibration, optical clocks and length metrology.

PMID- 19582113
TI  - Reversing the weak quantum measurement for a photonic qubit.
AB  - We demonstrate the conditional reversal of a weak (partial-collapse) quantum
      measurement on a photonic qubit. The weak quantum measurement causes a nonunitary
      transformation of a qubit which is subsequently reversed to the original state
      after a successful reversing operation. Both the weak measurement and the
      reversal operation are implemented linear optically. The state recovery fidelity,
      determined by quantum process tomography, is shown to be over 94% for partial
      collapse strength up to 0.9. We also experimentally study information gain due to
      the weak measurement and discuss the role of the reversing operation as an
      information erasure.

PMID- 19582114
TI  - Robust orthogonal parameterization of evolution strategy for adaptive laser pulse
      shaping.
AB  - Many spectroscopic applications of femtosecond laser pulses require properly
      shaped spectral phase profiles. The optimal phase profile can be programmed on
      the pulse by adaptive pulse shaping. A promising optimization algorithm for such
      adaptive experiments is evolution strategy (ES). Here, we report a four fold
      increase in the rate of convergence and ten percent increase in the final yield
      of the optimization, compared to the direct parameterization approach, by using a
      new version of ES in combination with Legendre polynomials and frequency-resolved
      detection. Such a fast learning rate is of paramount importance in spectroscopy
      for reducing the artifacts of laser drift, optical degradation, and
      precipitation.

PMID- 19582115
TI  - Highly sensitive size discrimination of sub-micron objects using optical Fourier
      processing based on two-dimensional Gabor filters.
AB  - We use optical Gabor-like filtering implemented with a digital micromirror device
      to achieve nanoscale sensitivity to changes in the size of finite and periodic
      objects imaged at low resolution. The method consists of applying an optical
      Fourier filter bank consisting of Gabor-like filters of varying periods and
      extracting the optimum filter period that maximizes the filtered object signal.
      Using this optimum filter period as a measure of object size, we show sensitivity
      to a 7.5 nm change in the period of a chirped phase mask with period around 1
      microm. We also show 30 nm sensitivity to change in the size of polystyrene
      spheres with diameters around 500 nm. Unlike digital post-processing our optical
      processing method retains its sensitivity when implemented at low magnification
      in undersampled images. Furthermore, the optimum Gabor filter period found
      experimentally is linearly related to sphere diameter over the range 0.46 microm
      1 microm and does not rely on a predictive scatter model such as Mie theory. The
      technique may have applications in high throughput optical analysis of
      subcellular morphology to study organelle function in living cells.

PMID- 19582116
TI  - Two-point-separation in a sub-micron nonscanning IR super-resolution microscope
      based on transient fluorescence detected IR spectroscopy.
AB  - IR absorption of chemical species in microscopic objects such as biological cells
      cannot be measured by conventional IR microscopes, because of their low
      resolution. To overcome this problem, we developed a novel far-field IR super
      resolution microscope employing transient fluorescence detected IR spectroscopy.
      The resolution of this microscope was shown to be 880 nm by measuring the image
      of 1 microm fluorescent beads. Furthermore, it succeeded in resolving beads
      located 1.4 microm apart from each other. This is considerably smaller than the
      diffraction limit of the applied IR light (3.4 microm). These results suggest the
      capability of our microscope to study sub-micron targets such as sub-cellular
      structures of biological cells.

PMID- 19582117
TI  - High performance photon-pair source based on a fiber-coupled periodically poled
      KTiOPO4 waveguide.
AB  - We demonstrate efficient generation of photon pairs at 1316 nm in a fiber-coupled
      type-II phase-matched Rb-indiffused waveguide in periodically poled KTiOPO(4).
      The integrated waveguide source has a pair production rate of 2 x 10(7)/s/mW in a
      1.08-nm bandwidth, in good agreement with a theoretical model that takes into
      account the transversal momentum imparted on the phase matching function by the
      waveguide. We achieve a Hong-Ou-Mandel quantum-interference visibility of 98.2%
      after subtraction of accidental coincidences, representing the highest reported
      value for a waveguide-based photon-pair source.

PMID- 19582119
TI  - Efficient frequency doubling of a femtosecond Yb:KGW laser in a BiB3O6 crystal.
AB  - Efficient frequency doubling of a high-power femtosecond Yb:KGW laser in a
      nonlinear BiBO crystal is demonstrated. Green second harmonic generation with
      more than 1.1 W of average power and 41% conversion efficiency was achieved using
      a single-pass configuration.

PMID- 19582118
TI  - Digital holographic microscopy for quantitative cell dynamic evaluation during
      laser microsurgery.
AB  - Digital holographic microscopy allows determination of dynamic changes in the
      optical thickness profile of a transparent object with sub-wavelength accuracy.
      Here, we report a quantitative phase laser microsurgery system for evaluation of
      cellular/ sub-cellular dynamic changes during laser micro-dissection. The
      proposed method takes advantage of the precise optical manipulation by the laser
      microbeam and quantitative phase imaging by digital holographic microscopy with
      high spatial and temporal resolution. This system will permit quantitative
      evaluation of the damage and/or the repair of the cell or cell organelles in real
      time.

PMID- 19582121
TI  - Reduction of the time-to-full-brightness in solid-state lasers using intra-cavity
      adaptive optics.
AB  - Several adaptive-optics techniques, based on the active modification of the
      optical properties of the laser cavity, were used to significantly reduce the
      time-to-full-brightness of solid-state lasers. Resonator re-configuration was
      achieved using a mechanical translation stage and both multi- and single-element
      deformable bimorph mirrors. Using these techniques the effects of thermally
      induced distortion in Nd:YLF and Nd:YAG lasers can be minimized and the warm-up
      time reduced by a factor of 3-6.

PMID- 19582120
TI  - Video-rate near infrared tomography to image pulsatile absorption properties in
      thick tissue.
AB  - A high frame-rate near-infrared (NIR) tomography system was created to allow
      transmission imaging of thick tissues with spectral encoding for parallel source
      implementation. The design was created to maximize tissue penetration through up
      to 10 cm of tissue, allowing eventual use in human imaging. Eight temperature
      controlled laser diodes (LD) are used in parallel with 1.5 nm shifts in their
      lasing wavelengths. Simultaneous detection is achieved with eight high
      resolution, CCD-based spectrometers that were synchronized to detect the
      intensities and decode their source locations from the spectrum. Static and
      dynamic imaging is demonstrated through a 64 mm tissue-equivalent phantom, with
      acquisition rates up to 20 frames per second. Imaging of pulsatile absorption
      changes through a 72 mm phantom was demonstrated with a 0.5 Hz varying object
      having only 1% effect upon the transmitted signal. This subtle signal change was
      used to show that while reconstructing the signal changes in a tissue may not be
      possible, image-guided recovery of the pulsatile change in broad regions of
      tissue was possible. The ability to image thick tissue and the capacity to image
      periodic changes in absorption makes this design well suited for tracking thick
      tissue hemodynamics in vivo during MR or CT imaging.

PMID- 19582122
TI  - Optical rogue wave statistics in laser filamentation.
AB  - We experimentally observed optical rogue wave statistics during high power
      femtosecond pulse filamentation in air. We characterized wavelength-dependent
      intensity fluctuations across 300 nm broadband filament spectra generated by
      pulses with several times the critical power for filamentation. We show how the
      statistics vary from a near-Gaussian distribution in the vicinity of the pump to
      a long tailed "L-shaped" distribution at the short wavelength and long wavelength
      edges. The results are interpreted in terms of pump noise transfer via self-phase
      modulation.

PMID- 19582123
TI  - Passively Q-switched dual-wavelength laser output of LD-end-pumped ceramic Nd:YAG
      laser.
AB  - We reported a dual-wavelength laser with a ceramic Nd:YAG as laser material and
      Cr:YAG as frequency selector and saturable absorber. Continuous-wave output power
      was achieved to be as high as 6.19 W at 1052 nm. With Cr:YAG, the laser has dual
      wavelength at 1052 and 1064 nm. The shortest pulse width, maximum pulse energy
      and highest peak power were 4.8 ns, 103.2 microJ, and 21.5 kW. This pulsed laser
      is possible to be used as a new source to generate terahertz radiation.

PMID- 19582124
TI  - Coupling between energy and phase in hollow-core fiber based f-to-2f
      interferometers.
AB  - The dependence of the carrier-envelope (CE) phase of the pulses from a hollow
      core fiber on the input laser energy was studied using two f-to- 2f
      interferometers. The CE phase in the in-loop f-to-2f interferometer was measured
      with the octave spanning white-light spectrum from the hollow-core fiber, whereas
      the out-of-loop interferometer was based on a sapphire plate. By modulating the
      input power of the in-loop interferometer and measuring the out-of-loop CE phase
      at the same time, the coupling coefficient between the measured CE phase and the
      laser energy for the hollow-core fiber was determined to be 128 mrad per 1%
      energy change .

PMID- 19582125
TI  - Security of a discretely signaled continuous variable quantum key distribution
      protocol for high rate systems.
AB  - We propose a continuous variable based quantum key distribution protocol that
      makes use of discretely signaled coherent light and reverse error reconciliation.
      We present a rigorous security proof against collective attacks with realistic
      lossy, noisy quantum channels, imperfect detector efficiency, and detector
      electronic noise. This protocol is promising for convenient, high-speed operation
      at link distances up to 50 km with the use of post-selection.

PMID- 19582126
TI  - Demonstration of a true single-shot 100 GHz-bandwidth optical oscilloscope at
      1053-1064 nm.
AB  - We demonstrate an innovating design to validate and to optimize the real-time
      performance of an all-optical oscilloscope at 1053-1064 nm. A unique broadband
      pulse is generated by means of frequency beats and of proper optical-shaping,
      which helps us to evidence a signal bandwidth of 100 GHz and a dynamics range in
      excess of 25 dB. Gain-narrowing and dispersion effects due to the replication of
      the input pulse are shown to be the first limitations in the broadband
      capabilities.

PMID- 19582127
TI  - Development of a non-uniform discrete Fourier transform based high speed spectral
      domain optical coherence tomography system.
AB  - We develop a high speed spectral domain optical coherence tomography (SD-OCT)
      system based on a custom-built spectrometer and non-uniform discrete Fourier
      transform (NDFT) to realize minimized depth dependent sensitivity fall-off. After
      precise spectral calibration of the spectrometer, NDFT of the acquired spectral
      data is adopted for image reconstruction. The spectrometer is able to measure a
      wavelength range of about 138 nm with a spectral resolution of 0.0674 nm at
      central wavelength of 835 nm, corresponding to an axial imaging range of 2.56 mm
      in air. Zemax simulations and sensitivity fall-off measurements under two
      alignment states of the spectrometer are given. Both theoretical simulations and
      experiments are done to study the depth dependent sensitivity of the developed
      system based on NDFT in contrast to those based on conventional discrete Fourier
      transform (DFT) with and without interpolation. In vivo imaging on human finger
      from volunteer is conducted at A-scan rate of 29 kHz and reconstruction is done
      based on different methods. The comparing results confirm that reconstruction
      method based on NDFT indeed improves sensitivity especially at large depth while
      maintaining the coherence-function-limited depth resolution.

PMID- 19582128
TI  - Ultimate spatial resolution with Diffuse Optical Tomography.
AB  - We evaluate the ultimate transverse spatial resolution that can be expected in
      Diffuse Optical Tomography, in the configuration of projection imaging. We show
      how such a performance can be approached using time-resolved measurements and
      reasonable assumptions, in the context of a linearized diffusion model.

PMID- 19582129
TI  - Sensitivity enhancement in grating coupled surface plasmon resonance by azimuthal
      control.
AB  - We present a method for improving the sensing capability of grating coupled
      surface plasmon resonance (GCSPR) sensors. The grating is rotated azimuthally
      (phi) until the excitation of double surface plasmon polaritions (SPPs) by a
      single wavelength is possible. Close to this condition, further tuning of the
      incident wavelength will merge the double SPPs into a multi-SPP resonance which
      is angularly broad but spectrally sharp. This is the condition where the momentum
      vector of the propagating SPP is perpendicular to the incident light momentum. We
      demonstrate this sensitivity enhancement on a Au grating surface using a
      dodecanethiol (C12) self-assembled monolayer (SAM). Using this method, a shift in
      resonance angle as large as 3 degrees can be observed. The simulated sensitivity
      of this method shows that a sensitivity up to 800 degrees /RIU is achievable,
      which is one order of magnitude greater than that in a conventional fixed grating
      (phi = 0 degrees ) as well as the prism-coupled Kretschmann configuration.

PMID- 19582130
TI  - Spatially and polarization resolved plasmon mediated transmission through
      continuous metal films.
AB  - The experimental demonstration and characterization is made of the plasmon
      mediated resonant transmission through an embedded undulated continuous thin
      metal film under normal incidence. 1D undulations are shown to enable a spatially
      resolved polarisation filtering whereas 2D undulations lead to spatially
      resolved, polarization independent transmission. Whereas the needed submicron
      microstructure lends itself in principle to CD-like low-cost mass replication by
      means of injection moulding and embossing, the present paper demonstrates the
      expected transmission effects on experimental models based on metal-coated
      photoresist gratings. The spectral and angular dependence in the neighbourhood of
      resonance are investigated and the question of the excess losses exhibited by
      surface plasmons is discussed.

PMID- 19582131
TI  - Frequency-switchable microwave generation based on a dual-wavelength single
      longitudinal-mode fiber laser incorporating a high-finesse ring filter.
AB  - A wavelength-switchable single-longitudinal-mode (SLM) dual-wavelength erbium
      doped fiber laser (EDFL) incorporating a novel high-finesse ring filter is
      proposed and demonstrated. The ring filter consists of two optical couplers and a
      section of pumped erbium-doped fiber (EDF). Thanks to the gain generated by the
      EDF, the ring filter has spectral response with a high finesse. The incorporation
      of the ring filter leads to the suppression of undesirable modes in the dual
      wavelength EDFL. An experiment is carried out. Two SLM wavelengths are generated.
      The side mode suppression ratio is greater than 50 dB. The wavelength spacing of
      the two wavelengths is tunable with a tuning step of approximately 10 GHz. A
      frequency switchable microwave signal from approximately 10 to approximately 40
      GHz is thus generated by beating the two wavelengths at a photodetector (PD). The
      spectral width of the generated microwave signal is measured to be less than 5
      kHz.

PMID- 19582132
TI  - Tellurite microstructure fibers with small hexagonal core for supercontinuum
      generation.
AB  - Tellurite glass microstructure fibers with a 1 microm hexagonal core were
      fabricated successfully by accurately controlling the temperature field in the
      fiber-drawing process. The diameter ratio of holey region to core (DRHC) for the
      fiber can be adjusted freely in the range of 1-20 by pumping a positive pressure
      into the holes when drawing fiber, which provides much freedom in engineering the
      chromatic dispersion. With the increase of DRHC from 3.5 to 20, the zero
      dispersion wavelengths were shifted several hundred nanometers, the cutoff
      wavelength due to confinement loss was increased from 1600 nm to 3800 nm, and the
      nonlinear coefficient gamma was increased from 3.9 to 5.7 W(-1)/m. Efficient
      visible emissions due to third harmonic generation were found for fibers with a
      DRHC of 10 and 20 under the 1557 nm pump of a femtosecond fiber laser. One octave
      flattened supercontinuum spectrum was generated from fibers with a DRHC of 3.5,
      10 and 20 by the 1064 nm pump of a picosecond fiber laser. To the best of our
      knowledge, we have for the first time fabricated a hexagonal core fiber by soft
      glass with such a small core size, and have demonstrated a large influence of the
      holey region on the dispersion, nonlinear coefficient and supercontinuum
      generation for such fiber.

PMID- 19582133
TI  - Multi-passband tunneling effect in multilayered Epsilon-Near-Zero Metamaterials.
AB  - Recently, several experimental results verified the tunneling effect theory of
      that the electromagnetic energy can be squeezed through an ultra-narrow channel
      filled with epsilon-near-zero (ENZ) medium. However, the energy squeezing can be
      only achieved in a narrow region. Here, we present a full-wave simulation of the
      tunneling effect in multilayered channels full of thin ENZ metamaterials with
      different plasma frequencies. Thin metallic wires arrays with different radiuses
      are employed to form these effective ENZ media, whose plasma frequencies are
      different. The appearance of several passbands in the transmission curve verifies
      that multi-passband energy tunneling effect can be implemented by multilayer ENZ
      channels. There are two possible reasons for these peaks, one is the ENZ
      tunneling effect, and the other is the Fabry-Perot resonance. For each
      transmission peak corresponding two-spatial maps of electric field are given, in
      order to distinguish the causes.

PMID- 19582134
TI  - Colored images generated by metallic sub-wavelength gratings.
AB  - Gratings with periods smaller than visible wavelengths in ambient white light
      will exhibit enhanced colors if the profile is designed so that resonant light
      interaction occurs in the visible range. Resonances have a frequency-selective
      influence to the grating diffraction inducing colors in transmittance and
      reflectance, respectively. Apart from the well-known surface-plasmon polariton
      excitations and cavity resonances, newly discovered resonances in TE-polarization
      can be exploited for colorizing wire-gratings, when simply illuminated by
      unpolarized white light. Colors can be laterally tuned by varying the grating
      profile. The capability of generating images by sub-wavelength gratings is
      exemplified by a metallic wire grating embedded in a plastic foil with a lateral
      variable modulation depth. This method for producing colored images is
      predestined for industrial mass production and will have ever more practical
      applications such as for security features.

PMID- 19582135
TI  - Three-channel all-optical routing in a Pr3+:Y2SiO5 crystal.
AB  - We experimentally demonstrate a three-channel all-optical routing based on light
      storage in a Pr(3+):Y(2)SiO(5) crystal. By switching off the control field under
      the condition of electromagnetically induced transparency, the optical
      information of the probe light pulse can be stored in the crystal. When three
      retrieve control fields are switched on in the release process, the stored
      optical information from one light channel can be transferred (or distributed)
      into three different light channels. Also we show that this all-optical routing
      can be time-delayed. Such a multichannel all-optical routing in solids may have
      practical applications in quantum information and all-optical network.

PMID- 19582136
TI  - SPECTROSCOPIC AND ELECTROCHEMICAL PROPERTIES OF 2-AMINOPHENOTHIAZINE.
AB  - Phenothiazines derivatives are versatile compounds that are used in many fields,
      depending on the type and position of the substitution on the parent molecule.
      The photochemical, photophysical and electrochemical properties of several
      phenothiazine derivatives have been previously reported in detail. However, no
      reports have been presented for 2-aminophenothiazine (APH), a candidate that
      provides for the further chemical modification and the introduction of specific
      substituents. In this work, the photophysical and electrochemical properties of
      APH were measured in acetonitrile. The APH ground state absorption and
      fluorescence spectrum (phi(f) < 0.01) are similar to the corresponding that of PH
      parent molecule. A mono exponential decay fluorescence lifetime of 0.65 ns was
      determined for APH in acetonitrile. Characterization of the 355 nm nanosecond
      laser flash photolysis transient species reveals the presence of the triplet
      triplet transient intermediate with a high intersystem crossing quantum yield
      (phi(T) = 0.72 +/- 0.07), indicating that the APH main excited state deactivation
      channel is intersystem crossing. The oxidation potential of APH is lower than
      phenothiazine parent molecule ((0.38 V vs 0.69 V vs Ag/AgCl(sat)). Altogether,
      these results show that APH has photochemical and photophysical properties
      similar to the phenothiazine parent molecule, but with the possibility of
      providing an amino functionality at 2-position for further chemical modification.

PMID- 19582137
TI  - Conflict, crisis, and abuse in Dharavi, Mumbai: experiences from six years at a
      centre for vulnerable women and children.
AB  - Nayreen Daruwalla and colleagues describe the Centre for Vulnerable Women and
      Children, which serves clients coping with crisis and violence in the urban
      setting of Dharavi, Mumbai.

PMID- 19582138
TI  - Improving the cost-effectiveness of artificial visual baits for controlling the
      tsetse fly Glossina fuscipes fuscipes.
AB  - Tsetse flies, which transmit sleeping sickness to humans and nagana to cattle,
      are commonly controlled by stationary artificial baits consisting of traps or
      insecticide-treated screens known as targets. In Kenya the use of electrocuting
      sampling devices showed that the numbers of Glossina fuscipes fuscipes (Newstead)
      visiting a biconical trap were nearly double those visiting a black target of 100
      cm x 100 cm. However, only 40% of the males and 21% of the females entered the
      trap, whereas 71% and 34%, respectively, alighted on the target. The greater
      number visiting the trap appeared to be due to its being largely blue, rather
      than being three-dimensional or raised above the ground. Through a series of
      variations of target design we show that a blue-and-black panel of cloth (0.06
      m(2)) flanked by a panel (0.06 m(2)) of fine black netting, placed at ground
      level, would be about ten times more cost-effective than traps or large targets
      in control campaigns. This finding has important implications for controlling all
      subspecies of G. fuscipes, which are currently responsible for more than 90% of
      sleeping sickness cases.

PMID- 19582139
TI  - The unfinished public health agenda of chagas disease in the era of
      globalization.

PMID- 19582140
TI  - Differential regional immune response in Chagas disease.
AB  - Following infection, lymphocytes expand exponentially and differentiate into
      effector cells to control infection and coordinate the multiple effector arms of
      the immune response. Soon after this expansion, the majority of antigen-specific
      lymphocytes die, thus keeping homeostasis, and a small pool of memory cells
      develops, providing long-term immunity to subsequent reinfection. The extent of
      infection and rate of pathogen clearance are thought to determine both the
      magnitude of cell expansion and the homeostatic contraction to a stable number of
      memory cells. This straight correlation between the kinetics of T cell response
      and the dynamics of lymphoid tissue cell numbers is a constant feature in acute
      infections yielded by pathogens that are cleared during the course of response.
      However, the regional dynamics of the immune response mounted against pathogens
      that are able to establish a persistent infection remain poorly understood.
      Herein we discuss the differential lymphocyte dynamics in distinct central and
      peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the
      causative agent of Chagas disease. While the thymus and mesenteric lymph nodes
      undergo a severe atrophy with massive lymphocyte depletion, the spleen and
      subcutaneous lymph nodes expand due to T and B cell activation/proliferation.
      These events are regulated by cytokines, as well as parasite-derived moieties. In
      this regard, identifying the molecular mechanisms underlying regional lymphocyte
      dynamics secondary to T. cruzi infection may hopefully contribute to the design
      of novel immune intervention strategies to control pathology in this infection.

PMID- 19582141
TI  - Regulated fluctuations in nanog expression mediate cell fate decisions in
      embryonic stem cells.
AB  - There is evidence that pluripotency of mouse embryonic stem (ES) cells is
      associated with the activity of a network of transcription factors with Sox2,
      Oct4, and Nanog at the core. Using fluorescent reporters for the expression of
      Nanog, we observed that a population of ES cells is best described by a dynamic
      distribution of Nanog expression characterized by two peaks defined by high (HN)
      and low (LN) Nanog expression. Typically, the LN state is 5%-20% of the total
      population, depending on the culture conditions. Modelling of the activity of
      Nanog reveals that a simple network of Oct4/Sox2 and Nanog activity can account
      for the observed distribution and its properties as long as the transcriptional
      activity is tuned by transcriptional noise. The model also predicts that the LN
      state is unstable, something that is born out experimentally. While in this
      state, cells can differentiate. We suggest that transcriptional fluctuations in
      Nanog expression are an essential element of the pluripotent state and that the
      function of Sox2, Oct4, and Nanog is to act as a network that promotes and
      maintains transcriptional noise to interfere with the differentiation signals.

PMID- 19582142
TI  - Feasibility, drug safety, and effectiveness of etiological treatment programs for
      Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of
      Medecins Sans Frontieres.
AB  - BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or
      anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly
      affecting populations in poor areas of Latin America, medical care for this
      neglected disease is often lacking. Medecins Sans Frontieres/Doctors Without
      Borders (MSF) has provided diagnostic and treatment services for Chagas disease
      since 1999. This report describes 10 years of field experience in four MSF
      programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols,
      safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to
      2008, MSF provided free diagnosis, etiological treatment, and follow-up care for
      patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999
      2002); Olopa, Guatemala (2003-2006); Entre Rios, Bolivia (2002-2006); and Sucre,
      Bolivia (2005-2008). Essential program components guaranteeing feasibility of
      implementation were information, education, and communication (IEC) at the
      community and family level; vector control; health staff training; screening and
      diagnosis; treatment and compliance, including family-based strategies for early
      detection of adverse events; and logistics. Chagas disease diagnosis was
      confirmed by testing blood samples using two different diagnostic tests. T. cruzi
      positive patients were treated with benznidazole as first-line treatment, with
      appropriate counseling, consent, and active participation from parents or
      guardians for daily administration of the drug, early detection of adverse
      events, and treatment withdrawal, when necessary. Weekly follow-up was conducted,
      with adverse events recorded to assess drug safety. Evaluations of serological
      conversion were carried out to measure treatment effectiveness. Vector control,
      entomological surveillance, and health education activities were carried out in
      all projects with close interaction with national and regional programs. RESULTS:
      Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa,
      Entre Rios, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of
      these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients,
      respectively, were diagnosed as seropositive. Patients were treated with
      benznidazole, and early findings of seroconversion varied widely between the
      Central and South American programs: 87.1% and 58.1% at 18 months post-treatment
      in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Rios; and 0% at
      an average of 18 months in Sucre. Benznidazole-related adverse events were
      observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa,
      respectively, and 25.6% and 37.9% of patients in Entre Rios and Sucre,
      respectively. Most adverse events were mild and manageable. No deaths occurred in
      the treatment population. CONCLUSIONS: These results demonstrate the feasibility
      of implementing Chagas disease diagnosis and treatment programs in resource
      limited settings, including remote rural areas, while addressing the limitations
      associated with drug-related adverse events. The variability in apparent
      treatment effectiveness may reflect differences in patient and parasite
      populations, and illustrates the limitations of current treatments and measures
      of efficacy. New treatments with improved safety profiles, pediatric formulations
      of existing and new drugs, and a faster, reliable test of cure are all urgently
      needed.

PMID- 19582144
TI  - Quality of DNA extracted from mouthwashes.
AB  - BACKGROUND: A cost effective, safe and efficient method of obtaining DNA samples
      is essential in large scale genetic analyses. Buccal cells are an attractive
      source of DNA, as their collection is non-invasive and can be carried out by
      mail. However, little attention has been given to the quality of DNA extracted
      from mouthwashes. METHODOLOGY: Mouthwash-derived DNA was extracted from 500
      subjects participating in a genetic study of high myopia. DNA quality was
      investigated using two standard techniques: agarose gel electrophoresis and
      quantitative polymerase chain reaction (qPCR). PRINCIPAL FINDINGS: Whereas the
      majority of mouthwash-derived DNA samples showed a single band of high molecular
      weight DNA by gel electrophoresis, 8.9% (95% CI: 7.1-10.7%) of samples contained
      only a smear of low-to-medium molecular weight, degraded DNA. The odds of DNA
      degradation in a subject's second mouthwash sample, given degradation of the
      first, was significantly greater than one (OR = 3.13; 95% CI: 1.22-7.39; Fisher's
      test P = 0.009), suggesting that DNA degradation was at least partially a subject
      specific phenomenon. Approximately 12.4% (95% CI: 10.4-14.4%) of mouthwash
      derived DNA failed to PCR amplify efficiently (using an approximately 200 bp
      microsatellite marker). However, we found there was no significant difference in
      amplification success rate between DNA samples judged to be degraded or non
      degraded by gel electrophoresis (Fisher's test P = 0.5). CONCLUSIONS: This study
      demonstrated that DNA degradation affects a significant minority of saline
      mouthwashes, and that the phenomenon is partially subject-specific. Whilst the
      level of degradation did not significantly prevent successful amplification of
      short PCR fragments, previous studies suggest that such DNA degradation would
      compromise more demanding applications.

PMID- 19582143
TI  - Repression of flowering by the miR172 target SMZ.
AB  - A small mobile protein, encoded by the FLOWERING LOCUS T (FT) locus, plays a
      central role in the control of flowering. FT is regulated positively by CONSTANS
      (CO), the output of the photoperiod pathway, and negatively by FLC, which
      integrates the effects of prolonged cold exposure. Here, we reveal the mechanisms
      of regulation by the microRNA miR172 target SCHLAFMUTZE (SMZ), a potent repressor
      of flowering. Whole-genome mapping of SMZ binding sites demonstrates not only
      direct regulation of FT, but also of many other flowering time regulators acting
      both upstream and downstream of FT, indicating an important role of miR172 and
      its targets in fine tuning the flowering response. A role for the miR172/SMZ
      module as a rheostat in flowering time is further supported by SMZ binding to
      several other genes encoding miR172 targets. Finally, we show that the action of
      SMZ is completely dependent on another floral repressor, FLM, providing the first
      direct connection between two important classes of flowering time regulators, AP2
      and MADS-domain proteins.

PMID- 19582145
TI  - Comparative expression profiling of Leishmania: modulation in gene expression
      between species and in different host genetic backgrounds.
AB  - BACKGROUND: Genome sequencing of Leishmania species that give rise to a range of
      disease phenotypes in the host has revealed highly conserved gene content and
      synteny across the genus. Only a small number of genes are differentially
      distributed between the three species sequenced to date, L. major, L. infantum
      and L. braziliensis. It is not yet known how many of these genes are expressed in
      the disease-promoting intracellular amastigotes of these species or whether genes
      conserved between the species are differentially expressed in the host.
      METHODS/PRINCIPAL FINDINGS: We have used customised oligonucleotide microarrays
      to confirm that all of the differentially distributed genes identified by genome
      comparisons are expressed in intracellular amastigotes, with only a few of these
      subject to regulation at the RNA level. In the first large-scale study of gene
      expression in L. braziliensis, we show that only approximately 9% of the genes
      analysed are regulated in their RNA expression during the L. braziliensis life
      cycle, a figure consistent with that observed in other Leishmania species.
      Comparing amastigote gene expression profiles between species confirms the
      proposal that Leishmania transcriptomes undergo little regulation but also
      identifies conserved genes that are regulated differently between species in the
      host. We have also investigated whether host immune competence influences
      parasite gene expression, by comparing RNA expression profiles in L. major
      amastigotes derived from either wild-type (BALB/c) or immunologically compromised
      (Rag2(-/-) gamma(c) (-/-)) mice. While parasite dissemination from the site of
      infection is enhanced in the Rag2(-/-) gamma(c) (-/-) genetic background,
      parasite RNA expression profiles are unperturbed. CONCLUSION/SIGNIFICANCE: These
      findings support the hypothesis that Leishmania amastigotes are pre-adapted for
      intracellular survival and undergo little dynamic modulation of gene expression
      at the RNA level. Species-specific parasite factors contributing to virulence and
      pathogenicity in the host may be limited to the products of a small number of
      differentially distributed genes or the differential regulation of conserved
      genes, either of which are subject to translational and/or post-translational
      controls.

PMID- 19582146
TI  - Time-warp-invariant neuronal processing.
AB  - Fluctuations in the temporal durations of sensory signals constitute a major
      source of variability within natural stimulus ensembles. The neuronal mechanisms
      through which sensory systems can stabilize perception against such fluctuations
      are largely unknown. An intriguing instantiation of such robustness occurs in
      human speech perception, which relies critically on temporal acoustic cues that
      are embedded in signals with highly variable duration. Across different instances
      of natural speech, auditory cues can undergo temporal warping that ranges from 2
      fold compression to 2-fold dilation without significant perceptual impairment.
      Here, we report that time-warp-invariant neuronal processing can be subserved by
      the shunting action of synaptic conductances that automatically rescales the
      effective integration time of postsynaptic neurons. We propose a novel spike
      based learning rule for synaptic conductances that adjusts the degree of synaptic
      shunting to the temporal processing requirements of a given task. Applying this
      general biophysical mechanism to the example of speech processing, we propose a
      neuronal network model for time-warp-invariant word discrimination and
      demonstrate its excellent performance on a standard benchmark speech-recognition
      task. Our results demonstrate the important functional role of synaptic
      conductances in spike-based neuronal information processing and learning. The
      biophysics of temporal integration at neuronal membranes can endow sensory
      pathways with powerful time-warp-invariant computational capabilities.

PMID- 19582147
TI  - Predator-induced changes in metabolism cannot explain the growth/predation risk
      tradeoff.
AB  - Defence against predators is usually accompanied by declining rates of growth or
      development. The classical growth/predation risk tradeoff assumes reduced
      activity as the cause of these declines. However, in many cases these costs
      cannot be explained by reduced foraging effort or enhanced allocation to
      defensive structures under predation risk. Here, we tested for a physiological
      origin of defence costs by measuring oxygen consumption in tadpoles (Rana
      temporaria) exposed to predation risk over short and long periods of time. The
      short term reaction was an increase in oxygen consumption, consistent with the
      "fight-or-flight" response observed in many organisms. The long term reaction
      showed the opposite pattern: tadpoles reduced oxygen consumption after three
      weeks exposure to predators, which would act to reduce the growth cost of
      predator defence. The results point to an instantaneous and reversible stress
      response to predation risk. This suggests that the tradeoff between avoiding
      predators and growing rapidly is not caused by changes in metabolic rate, and
      must be sought in other behavioural or physiological processes.

PMID- 19582148
TI  - Translational control of FOG-2 expression in cardiomyocytes by microRNA-130a.
AB  - MicroRNAs are increasingly being recognized as regulators of embryonic
      development; however, relatively few microRNAs have been identified to regulate
      cardiac development. FOG-2 (also known as zfpm2) is a transcriptional co-factor
      that we have previously shown is critical for cardiac development. In this
      report, we demonstrate that FOG-2 expression is controlled at the translational
      level by microRNA-130a. We identified a conserved region in the FOG-2 3'
      untranslated region predicted to be a target for miR-130a. To test the functional
      significance of this site, we generated an expression construct containing the
      luciferase coding region fused with the 3' untranslated region of FOG-2 or a
      mutant version lacking this microRNA binding site. When these constructs were
      transfected into NIH 3T3 fibroblasts (which are known to express miR-130a), we
      observed a 3.3-fold increase in translational efficiency when the microRNA target
      site was disrupted. Moreover, knockdown of miR-130a in fibroblasts resulted in a
      3.6-fold increase in translational efficiency. We also demonstrate that
      cardiomyocytes express miR-130a and can attenuate translation of mRNAs with a FOG
      2 3' untranslated region. Finally, we generated transgenic mice with
      cardiomyocyte over-expression of miR-130a. In the hearts of these mice, FOG-2
      protein levels were reduced by as much as 80%. Histological analysis of
      transgenic embryos revealed ventricular wall hypoplasia and ventricular septal
      defects, similar to that seen in FOG-2 deficient hearts. These results
      demonstrate the importance of miR-130a for the regulation of FOG-2 protein
      expression and suggest that miR-130a may also play a role in the regulation of
      cardiac development.

PMID- 19582150
TI  - Seasonal movements, aggregations and diving behavior of Atlantic bluefin tuna
      (Thunnus thynnus) revealed with archival tags.
AB  - Electronic tags were used to examine the seasonal movements, aggregations and
      diving behaviors of Atlantic bluefin tuna (Thunnus thynnus) to better understand
      their migration ecology and oceanic habitat utilization. Implantable archival
      tags (n = 561) were deployed in bluefin tuna from 1996 to 2005 and 106 tags were
      recovered. Movement paths of the fish were reconstructed using light level and
      sea-surface-temperature-based geolocation estimates. To quantify habitat
      utilization we employed a weighted kernel estimation technique that removed the
      biases of deployment location and track length. Throughout the North Atlantic,
      high residence times (167+/-33 days) were identified in four spatially confined
      regions on a seasonal scale. Within each region, bluefin tuna experienced
      distinct temperature regimes and displayed different diving behaviors. The mean
      diving depths within the high-use areas were significantly shallower and the dive
      frequency and the variance in internal temperature significantly higher than
      during transit movements between the high-use areas. Residence time in the more
      northern latitude high-use areas was significantly correlated with levels of
      primary productivity. The regions of aggregation are associated with areas of
      abundant prey and potentially represent critical foraging habitats that have
      seasonally abundant prey. Throughout the North Atlantic mean diving depth was
      significantly correlated with the depth of the thermocline, and dive behavior
      changed in relation to the stratification of the water column. In this study,
      with numerous multi-year tracks, there appear to be repeatable patterns of clear
      aggregation areas that potentially are changing with environmental conditions.
      The high concentrations of bluefin tuna in predictable locations indicate that
      Atlantic bluefin tuna are vulnerable to concentrated fishing efforts in the
      regions of foraging aggregations.

PMID- 19582149
TI  - The complex regulation of HIC (Human I-mfa domain containing protein) expression.
AB  - Human I-mfa domain containing protein (HIC) differentially regulates
      transcription from viral promoters. HIC affects the Wnt pathway, the JNK/SAPK
      pathway and the activity of positive transcription elongation factor-b (P-TEFb).
      Studies exploring HIC function in mammalian cells used ectopically expressed HIC
      due to undetected endogenous HIC protein. HIC mRNA contains exceptionally long 5'
      and 3' untranslated regions (UTRs) compared to the average length of mRNA UTRs.
      Here we show that HIC protein is subject to strict repression at multiple levels.
      The HIC mRNA UTRs reduce the expression of HIC or of a reporter protein: The HIC
      3'-UTR decreases both HIC and reporter mRNA levels, whereas upstream open reading
      frames located in the 5'-UTR repress the translation of HIC or of the reporter
      protein. In addition, ectopically expressed HIC protein is degraded by the
      proteasome, with a half-life of approximately 1 h, suggesting that upon
      activation, HIC expression in cells may be transient. The strict regulation of
      HIC expression at the levels of mRNA stability, translation efficiency and
      protein stability suggests that expression of the HIC protein and its involvement
      in the various pathways is required only under specific cellular conditions.

PMID- 19582151
TI  - Proinflammatory and Th2 cytokines regulate the high affinity IgE receptor
      (FcepsilonRI) and IgE-dependant activation of human airway smooth muscle cells.
AB  - BACKGROUND: The high affinity IgE receptor (FcepsilonRI) is a crucial structure
      for IgE-mediated allergic reactions. We have previously demonstrated that human
      airway smooth muscle (ASM) cells express the tetrameric (alphabetagamma2)
      FcepsilonRI, and its activation leads to marked transient increases in
      intracellular Ca(2+) concentration, release of Th-2 cytokines and eotaxin
      1/CCL11. Therefore, it was of utmost importance to delineate the factors
      regulating the expression of FcepsilonRI in human (ASM) cells.
      METHODOLOGY/PRINCIPAL FINDINGS: Incubation of human bronchial and tracheal smooth
      muscle (B/TSM) cells with TNF-alpha, IL-1beta or IL-4 resulted in a significant
      increase in FcepsilonRI-alpha chain mRNA expression (p<0.05); and TNF-alpha, IL-4
      enhanced the FcepsilonRI-alpha protein expression compared to the unstimulated
      control at 24, 72 hrs after stimulation. Interestingly, among all other
      cytokines, only TNF-alpha upregulated the FcepsilonRI-gamma mRNA expression.
      FcepsilonRI-gamma protein expression remained unchanged despite the nature of
      stimulation. Of note, as a functional consequence of FcepsilonRI upregulation,
      TNF-alpha pre-sensitization of B/TSM potentially augmented the CC (eotaxin
      1/CCL11 and RANTES/CCL5, but not TARC/CCL17) and CXC (IL-8/CXCL8, IP-10/CXCL10)
      chemokines release following IgE stimulation (p<0.05, n = 3). Furthermore, IgE
      sensitization of B/TSM cells significantly enhanced the transcription of
      selective CC and CXC chemokines at promoter level compared to control, which was
      abolished by Lentivirus-mediated silencing of Syk expression.
      CONCLUSIONS/SIGNIFICANCE: Our data depict a critical role of B/TSM in allergic
      airway inflammation via potentially novel mechanisms involving proinflammatory,
      Th2 cytokines and IgE/FcepsilonRI complex.

PMID- 19582152
TI  - Sex is always well worth its two-fold cost.
AB  - Sex is considered as an evolutionary paradox, since its positive contribution to
      Darwinian fitness remains unverified for some species. Defenses against
      unpredictable threats (parasites, fluctuating environment and deleterious
      mutations) are indeed significantly improved by wider genetic variability and by
      positive epistasis gained by sexual reproduction. The corresponding evolutionary
      advantages, however, do not overcome universally the barrier of the two-fold cost
      for sharing half of one's offspring genome with another member of the population.
      Here we show that sexual reproduction emerges and is maintained even when its
      Darwinian fitness is twice as low as the fitness of asexuals. We also show that
      more than two sexes (inheritance of genetic material from three or even more
      parents) are always evolutionary unstable. Our approach generalizes the
      evolutionary game theory to analyze species whose members are able to sense the
      sexual state of their conspecifics and to adapt their own sex consequently,
      either by switching or by taxis towards the highest concentration of the
      complementary sex. The widespread emergence and maintenance of sex follows
      therefore from its co-evolution with the even more widespread environmental
      sensing abilities.

PMID- 19582153
TI  - Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian
      fear conditioning.
AB  - BACKGROUND: Associative conditioning is a ubiquitous form of learning throughout
      the animal kingdom and fear conditioning is one of the most widely researched
      models for studying its neurobiological basis. Fear conditioning is also
      considered a model system for understanding phobias and anxiety disorders. A
      fundamental issue in fear conditioning regards the existence and location of
      neurons in the brain that receive convergent information about the conditioned
      stimulus (CS) and unconditioned stimulus (US) during the acquisition of
      conditioned fear memory. Convergent activation of neurons is generally viewed as
      a key event for fear learning, yet there has been almost no direct evidence of
      this critical event in the mammalian brain. METHODOLOGY/PRINCIPAL FINDINGS: Here,
      we used Arc cellular compartmental analysis of temporal gene transcription by
      fluorescence in situ hybridization (catFISH) to identify neurons activated during
      single trial contextual fear conditioning in rats. To conform to temporal
      requirements of catFISH analysis we used a novel delayed contextual fear
      conditioning protocol which yields significant single- trial fear conditioning
      with temporal parameters amenable to catFISH analysis. Analysis yielded clear
      evidence that a population of BLA neurons receives convergent CS and US
      information at the time of the learning, that this only occurs when the CS-US
      arrangement is supportive of the learning, and that this process requires N
      methyl-D-aspartate receptor activation. In contrast, CS-US convergence was not
      observed in dorsal hippocampus. CONCLUSIONS/SIGNIFICANCE: Based on the pattern of
      Arc activation seen in conditioning and control groups, we propose that a key
      requirement for CS-US convergence onto BLA neurons is the potentiation of US
      responding by prior exposure to a novel CS. Our results also support the view
      that contextual fear memories are encoded in the amygdala and that the role of
      dorsal hippocampus is to process and transmit contextual CS information.

PMID- 19582154
TI  - Allogeneic non-adherent bone marrow cells facilitate hematopoietic recovery but
      do not lead to allogeneic engraftment.
AB  - BACKGROUND: Non adherent bone marrow derived cells (NA-BMCs) have recently been
      described to give rise to multiple mesenchymal phenotypes and have an impact in
      tissue regeneration. Therefore, the effects of murine bone marrow derived NA-BMCs
      were investigated with regard to engraftment capacities in allogeneic and
      syngeneic stem cell transplantation using transgenic, human CD4(+), murine CD4(-/
      ), HLA-DR3(+) mice. METHODOLOGY/PRINCIPAL FINDINGS: Bone marrow cells were
      harvested from C57Bl/6 and Balb/c wild-type mice, expanded to NA-BMCs for 4 days
      and characterized by flow cytometry before transplantation in lethally irradiated
      recipient mice. Chimerism was detected using flow cytometry for MHC-I (H-2D[b], H
      2K[d]), mu/huCD4, and huHLA-DR3). Culturing of bone marrow cells in a
      dexamethasone containing DMEM medium induced expansion of non adherent cells
      expressing CD11b, CD45, and CD90. Analysis of the CD45(+) showed depletion of
      CD4(+), CD8(+), CD19(+), and CD117(+) cells. Expanded syngeneic and allogeneic NA
      BMCs were transplanted into triple transgenic mice. Syngeneic NA-BMCs protected
      83% of mice from death (n = 8, CD4(+) donor chimerism of 5.8+/-2.4% [day 40],
      P<.001). Allogeneic NA-BMCs preserved 62.5% (n = 8) of mice from death without
      detectable hematopoietic donor chimerism. Transplantation of syngeneic bone
      marrow cells preserved 100%, transplantation of allogeneic bone marrow cells 33%
      of mice from death. CONCLUSIONS/SIGNIFICANCE: NA-BMCs triggered endogenous
      hematopoiesis and induced faster recovery compared to bone marrow controls. These
      findings may be of relevance in the refinement of strategies in the treatment of
      hematological malignancies.

PMID- 19582155
TI  - Evolutionary insights from a genetically divergent hantavirus harbored by the
      European common mole (Talpa europaea).
AB  - BACKGROUND: The discovery of genetically distinct hantaviruses in shrews (Order
      Soricomorpha, Family Soricidae) from widely separated geographic regions
      challenges the hypothesis that rodents (Order Rodentia, Family Muridae and
      Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts
      that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes
      have been detected in moles of the Family Talpidae, including the Japanese shrew
      mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We
      present new insights into the evolutionary history of hantaviruses gained from a
      highly divergent hantavirus, designated Nova virus (NVAV), identified in the
      European common mole (Talpa europaea) captured in Hungary. METHODOLOGY/PRINCIPAL
      FINDINGS: Pair-wise alignment and comparison of the full-length S- and L-genomic
      segments indicated moderately low sequence similarity of 54-65% and 46-63% at the
      nucleotide and amino acid levels, respectively, between NVAV and representative
      rodent- and soricid-borne hantaviruses. Despite the high degree of sequence
      divergence, the predicted secondary structure of the NVAV nucleocapsid protein
      exhibited the characteristic coiled-coil domains at the amino-terminal end, and
      the L-segment motifs, typically found in hantaviruses, were well conserved.
      Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that
      NVAV formed a distinct clade that was evolutionarily distant from all other
      hantaviruses. CONCLUSIONS: Newly identified hantaviruses harbored by shrews and
      moles support long-standing virus-host relationships and suggest that ancestral
      soricomorphs, rather than rodents, may have been the early or original mammalian
      hosts.

PMID- 19582156
TI  - Age, but not experience, affects courtship gene expression in male Drosophila
      melanogaster.
AB  - Mutation screens in model organisms have helped identify the foundation of many
      fundamental organismal phenotypes. An emerging question in evolutionary and
      behavioral biology is the extent to which these "developmental" genes contribute
      to the subtle individual variation that characterizes natural populations. A
      related question is whether individual differences arise from static differences
      in gene expression that arose during previous life stages, or whether they are
      due to dynamic regulation of expression during the life stage under
      investigation. Here, we address these questions using genes that have been
      discovered to control the development of normal courtship behavior in male
      Drosophila melanogaster. We examined whether these genes have static or dynamic
      expression in the heads of adult male flies of different ages and with different
      levels of social experience. We found that 16 genes of the 25 genes examined were
      statically expressed, and 9 genes were dynamically expressed with changes related
      to adult age. No genes exhibited rapid dynamic expression changes due to social
      experience or age*experience interaction. We therefore conclude that a majority
      of fly "courtship" genes are statically expressed, while a minority are regulated
      in adults with respect to age, but not with respect to relevant social
      experience. These results are consistent with those from a recent microarray
      analysis that found none of the canonical courtship genes changed expression in
      male flies after brief exposure to females.

PMID- 19582157
TI  - Absence of p55 TNF receptor reduces atherosclerosis, but has no major effect on
      angiotensin II induced aneurysms in LDL receptor deficient mice.
AB  - BACKGROUND: The aim of the current study was to investigate the role of p55 TNF
      Receptor (p55 TNFR), the main signaling receptor for the pro-inflammatory
      cytokine tumor necrosis factor (TNF), in the development of two vascular
      disorders: atherosclerosis and angiotensin (Ang) II-induced abdominal aortic
      aneurysms (AAA). METHODOLOGY/PRINCIPAL FINDINGS: p55 TNFR deficient mice were
      crossed to an LDL receptor deficient background and were induced for the
      development of either atherosclerosis or AngII-induced AAA, and compared to
      littermate controls, wild-type for p55 TNFR expression. p55 TNFR deficient mice
      developed 43% smaller atherosclerotic lesions in the aortic sinuses compared to
      controls. Moreover, expression of CD68, a macrophage specific marker, exhibited a
      50% reduction in the aortic arches. Decreased atherosclerosis correlated with a
      strong down-regulation in the expression of adhesion molecules, such as VCAM-1
      and ICAM-1, by p55 TNFR deficient endothelium. In addition, expression levels of
      the pro-inflammatory cytokines and chemokines TNF, IL-6, MCP-1 and RANTES were
      significantly reduced in aortas of p55 TNFR deficient mice. In contrast, in the
      AngII-induced model of AAA, p55 TNFR deficiency correlated with a slight trend
      towards increased aneurismal lethality, but the incidence of aortic rupture due
      to a dissecting aneurysm, and the expansion of the suprarenal aorta were not
      significantly different compared to controls. CONCLUSION/SIGNIFICANCE: We found
      that p55 TNFR expression promotes atherosclerosis, among other mechanisms, by
      enhancing expression of endothelial adhesion molecules, while it seems to have no
      major role in the development of AngII-induced AAA.

PMID- 19582158
TI  - The incidence risk, clustering, and clinical presentation of La Crosse virus
      infections in the eastern United States, 2003-2007.
AB  - BACKGROUND: Although La Crosse virus (LACV) is one of the most common causes of
      pediatric arboviral infections in the United States, little has been done to
      assess its geographic distribution, identify areas of higher risk of disease, and
      to provide a national picture of its clinical presentation. Therefore, the
      objective of this study was to investigate the geographic distribution of LACV
      infections reported in the United States, to identify hot-spots of infection, and
      to present its clinical picture. METHODS AND FINDINGS: Descriptive and cluster
      analyses were performed on probable and confirmed cases of LACV infections
      reported to the Centers for Disease Control and Prevention from 2003-2007. A
      total of 282 patients had reported confirmed LACV infections during the study
      period. Of these cases the majority (81 percent) presented during the summer,
      occurred in children 15 years and younger (83.3 percent), and were found in male
      children (64.9 percent). Clinically, the infections presented as
      meningioencephalitis (56.3 percent), encephalitis (20.7 percent), meningitis
      (17.2 percent), or uncomplicated fever (5 percent). Deaths occurred in 1.9
      percent of confirmed cases, and in 8.6 percent of patients suffering from
      encephalitis. The majority of these deaths were in patients 15 years and younger.
      The county-level incidence risk among counties (n = 136) reporting both probable
      and confirmed cases for children 15 years and younger (n = 355) ranged from 0.2
      to 228.7 per 100,000 persons. The southern United States experienced a
      significantly higher (p<0.05) incidence risk during the months of June, July,
      August, and October then the northern United States. There was significant
      (p<0.05) clustering of high risk in several geographic regions with three deaths
      attributed to complications from LAC encephalitis occurring in two of these hot
      spots of infections. CONCLUSIONS: Both the incidence risk and case fatality rates
      were found to be higher than previously reported. We detected clustering in four
      geographic regions, a shift from the prior geographic distributions, and
      developed maps identifying high-risk areas. These findings are useful for raising
      awareness among health care providers regarding areas at a high risk of
      infections and for guiding targeted multifaceted interventions by public health
      officials.

PMID- 19582159
TI  - microRNA expression during trophectoderm specification.
AB  - BACKGROUND: Segregation of the trophectoderm from the inner cell mass of the
      embryo represents the first cell-fate decision of mammalian development.
      Transcription factors essential for specifying trophectoderm have been
      identified, but the role of microRNAs (miRNAs) in modulating this fate-choice has
      been largely unexplored. We have compared miRNA expression in embryonic stem cell
      (ESC)-derived trophectoderm and in staged murine embryos to identify a set of
      candidate miRNAs likely to be involved in trophectoderm specification. RESULTS:
      We profiled embryonic stem cells (ESCs) as they were induced to differentiate
      into trophectodermal cells by ectopic expression of HRas/Q61L. We also profiled
      murine embryos at progressive stages of preimplantation development (zygote, 2
      cell, 4-cell, 8-cell, morula, and blastocyst), which includes the time window in
      which the trophectoderm is specified in vivo Q61L/H. CONCLUSIONS: We describe
      miRNA expression changes that occur during trophectoderm specification and
      validate that our in vitro system faithfully recapitulates trophectoderm
      specification in vivo. By comparing our in vitro and in vivo datasets, we have
      identified a minimal set of candidate miRNAs likely to play a role in
      trophectoderm specification. These miRNAs are predicted to regulate a host of
      development-associated target genes, and many of these miRNAs have previously
      reported roles in development and differentiation. Additionally, we highlight a
      number of miRNAs whose tight developmental regulation may reflect a functional
      role in other stages of embryogenesis. Our embryo profiling data may be useful to
      investigators studying trophectoderm specification and other stages of
      preimplantation development.

PMID- 19582160
TI  - Molecular profiling of breast cancer cell lines defines relevant tumor models and
      provides a resource for cancer gene discovery.
AB  - BACKGROUND: Breast cancer cell lines have been used widely to investigate breast
      cancer pathobiology and new therapies. Breast cancer is a molecularly
      heterogeneous disease, and it is important to understand how well and which cell
      lines best model that diversity. In particular, microarray studies have
      identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like
      and normal-like-with characteristic gene-expression patterns and underlying DNA
      copy number alterations (CNAs). Here, we studied a collection of breast cancer
      cell lines to catalog molecular profiles and to assess their relation to breast
      cancer subtypes. METHODS: Whole-genome DNA microarrays were used to profile gene
      expression and CNAs in a collection of 52 widely-used breast cancer cell lines,
      and comparisons were made to existing profiles of primary breast tumors.
      Hierarchical clustering was used to identify gene-expression subtypes, and Gene
      Set Enrichment Analysis (GSEA) to discover biological features of those subtypes.
      Genomic and transcriptional profiles were integrated to discover within high
      amplitude CNAs candidate cancer genes with coordinately altered gene copy number
      and expression. FINDINGS: Transcriptional profiling of breast cancer cell lines
      identified one luminal and two basal-like (A and B) subtypes. Luminal lines
      displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors,
      basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled
      basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor
      cell characteristics. Compared to tumors, cell lines exhibited similar patterns
      of CNA, but an overall higher complexity of CNA (genetically simple luminal-A
      tumors were not represented), and only partial conservation of subtype-specific
      CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions,
      and the resident genes with concomitantly altered gene-expression, highlighting
      known and novel candidate breast cancer genes. CONCLUSIONS: Overall, breast
      cancer cell lines were genetically more complex than tumors, but retained
      expression patterns with relevance to the luminal-basal subtype distinction. The
      compendium of molecular profiles defines cell lines suitable for investigations
      of subtype-specific pathobiology, cancer stem cell biology, biomarkers and
      therapies, and provides a resource for discovery of new breast cancer genes.

PMID- 19582161
TI  - Heritable and lineage-specific gene knockdown in zebrafish embryo.
AB  - BACKGROUND: Reduced expression of developmentally important genes and tumor
      suppressors due to haploinsufficiency or epigenetic suppression has been shown to
      contribute to the pathogenesis of various malignancies. However, methodology that
      allows spatio-temporally knockdown of gene expression in various model organisms
      such as zebrafish has not been well established, which largely limits the
      potential of zebrafish as a vertebrate model of human malignant disorders.
      PRINCIPAL FINDING: Here, we report that multiple copies of small hairpin RNA
      (shRNA) are expressed from a single transcript that mimics the natural microRNA
      30e precursor (mir-shRNA). The mir-shRNA, when microinjected into zebrafish
      embryos, induced an efficient knockdown of two developmentally essential genes
      chordin and alpha-catenin in a dose-controllable fashion. Furthermore, we
      designed a novel cassette vector to simultaneously express an intronic mir-shRNA
      and a chimeric red fluorescent protein driven by lineage-specific promoter, which
      efficiently reduced the expression of a chromosomally integrated reporter gene
      and an endogenously expressed gata-1 gene in the developing erythroid progenitors
      and hemangioblasts, respectively. SIGNIFICANCE: This methodology provides an
      invaluable tool to knockdown developmental important genes in a tissue-specific
      manner or to establish animal models, in which the gene dosage is critically
      important in the pathogenesis of human disorders. The strategy should be also
      applicable to other model organisms.

PMID- 19582162
TI  - Fibrils from designed non-amyloid-related synthetic peptides induce AA
      amyloidosis during inflammation in an animal model.
AB  - BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like
      mechanism where amyloid fibrils act by seeding. Synthetic peptides with no
      amyloid relationship can assemble into amyloid-like fibrils and these may have
      seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic
      peptides, designed for nanotechnology, have been examined for their ability to
      produce fibrils with Congo red affinity and concomitant green birefringence,
      affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown
      that some amphiphilic fibril-forming peptides not only produced Congo red
      birefringence and showed affinity for thioflavin S, but they also shortened the
      lag phase for systemic AA-amyloidosis in mice when they were given intravenously
      at the time of inflammatory induction with silver nitride. Peptides, not forming
      amyloid-like fibrils, did not have such properties. CONCLUSIONS: These
      observations should caution researchers and those who work with synthetic
      peptides and their derivatives to be aware of the potential health concerns.

PMID- 19582163
TI  - New, improved treatments for Chagas disease: from the R&D pipeline to the
      patients.

PMID- 19582164
TI  - IL-12 can target human lung adenocarcinoma cells and normal bronchial epithelial
      cells surrounding tumor lesions.
AB  - BACKGROUND: Non small cell lung cancer (NSCLC) is a leading cause of cancer
      death. We have shown previously that IL-12rb2 KO mice develop spontaneously lung
      adenocarcinomas or bronchioalveolar carcinomas. Aim of the study was to
      investigate i) IL-12Rbeta2 expression in human primary lung adenocarcinomas and
      in their counterparts, i.e. normal bronchial epithelial cells (NBEC), ii) the
      direct anti-tumor activity of IL-12 on lung adenocarcinoma cells in vitro and
      vivo, and the mechanisms involved, and iii) IL-12 activity on NBEC.
      METHODOLOGY/PRINCIPAL FINDINGS: Stage I lung adenocarcinomas showed significantly
      (P = 0.012) higher frequency of IL-12Rbeta2 expressing samples than stage II/III
      tumors. IL-12 treatment of IL-12R(+) neoplastic cells isolated from primary
      adenocarcinoma (n = 6) inhibited angiogenesis in vitro through down-regulation of
      different pro-angiogenic genes (e.g. IL-6, VEGF-C, VEGF-D, and laminin-5), as
      assessed by chorioallantoic membrane (CAM) assay and PCR array. In order to
      perform in vivo studies, the Calu6 NSCLC cell line was transfected with the IL
      12RB2 containing plasmid (Calu6/beta2). Similar to that observed in primary
      tumors, IL-12 treatment of Calu6/beta2(+) cells inhibited angiogenesis in vitro.
      Tumors formed by Calu6/beta2 cells in SCID/NOD mice, inoculated subcutaneously or
      orthotopically, were significantly smaller following IL-12 vs PBS treatment due
      to inhibition of angiogenesis, and of IL-6 and VEGF-C production. Explanted
      tumors were studied by histology, immuno-histochemistry and PCR array. NBEC cells
      were isolated and cultured from lung specimens of non neoplastic origin. NBEC
      expressed IL-12R and released constitutively tumor promoting cytokines (e.g. IL-6
      and CCL2). Treatment of NBEC with IL-12 down-regulated production of these
      cytokines. CONCLUSIONS: This study demonstrates that IL-12 inhibits directly the
      growth of human lung adenocarcinoma and targets the adjacent NBEC. These novel
      anti-tumor activities of IL-12 add to the well known immune-modulatory properties
      of the cytokine and may provide a rational basis for the development of a
      clinical trial.

PMID- 19582165
TI  - Rhythms of consciousness: binocular rivalry reveals large-scale oscillatory
      network dynamics mediating visual perception.
AB  - Consciousness has been proposed to emerge from functionally integrated large
      scale ensembles of gamma-synchronous neural populations that form and dissolve at
      a frequency in the theta band. We propose that discrete moments of perceptual
      experience are implemented by transient gamma-band synchronization of relevant
      cortical regions, and that disintegration and reintegration of these assemblies
      is time-locked to ongoing theta oscillations. In support of this hypothesis we
      provide evidence that (1) perceptual switching during binocular rivalry is time
      locked to gamma-band synchronizations which recur at a theta rate, indicating
      that the onset of new conscious percepts coincides with the emergence of a new
      gamma-synchronous assembly that is locked to an ongoing theta rhythm; (2)
      localization of the generators of these gamma rhythms reveals recurrent
      prefrontal and parietal sources; (3) theta modulation of gamma-band
      synchronization is observed between and within the activated brain regions. These
      results suggest that ongoing theta-modulated-gamma mechanisms periodically
      reintegrate a large-scale prefrontal-parietal network critical for perceptual
      experience. Moreover, activation and network inclusion of inferior temporal
      cortex and motor cortex uniquely occurs on the cycle immediately preceding
      responses signaling perceptual switching. This suggests that the essential
      prefrontal-parietal oscillatory network is expanded to include additional
      cortical regions relevant to tasks and perceptions furnishing consciousness at
      that moment, in this case image processing and response initiation, and that
      these activations occur within a time frame consistent with the notion that
      conscious processes directly affect behaviour.

PMID- 19582167
TI  - The pitcher plant Sarracenia purpurea can directly acquire organic nitrogen and
      short-circuit the inorganic nitrogen cycle.
AB  - BACKGROUND: Despite the large stocks of organic nitrogen in soil, nitrogen
      availability limits plant growth in many terrestrial ecosystems because most
      plants take up only inorganic nitrogen, not organic nitrogen. Although some
      vascular plants can assimilate organic nitrogen directly, only recently has
      organic nitrogen been found to contribute significantly to the nutrient budget of
      any plant. Carnivorous plants grow in extremely nutrient-poor environments and
      carnivory has evolved in these plants as an alternative pathway for obtaining
      nutrients. We tested if the carnivorous pitcher plant Sarracenia purpurea could
      directly take up intact amino acids in the field and compared uptake of organic
      and inorganic forms of nitrogen across a gradient of nitrogen deposition. We
      hypothesized that the contribution of organic nitrogen to the nitrogen budget of
      the pitcher plant would decline with increasing nitrogen deposition. METHODOLOGY
      AND PRINCIPAL FINDINGS: At sites in Canada (low nitrogen deposition) and the
      United States (high nitrogen deposition), individual pitchers were fed two amino
      acids, glycine and phenylalanine, and inorganic nitrogen (as ammonium nitrate),
      individually and in mixture. Plants took up intact amino acids. Acquisition of
      each form of nitrogen provided in isolation exceeded uptake of the same form in
      mixture. At the high deposition site, uptake of organic nitrogen was higher than
      uptake of inorganic nitrogen. At the low deposition site, uptake of all three
      forms of nitrogen was similar. Completeness of the associated detritus-based food
      web that inhabits pitcher-plant leaves and breaks down captured prey had no
      effect on nitrogen uptake. CONCLUSIONS AND SIGNIFICANCE: By taking up intact
      amino acids, Sarracenia purpurea can short-circuit the inorganic nitrogen cycle,
      thus minimizing potential bottlenecks in nitrogen availability that result from
      the plant's reliance for nitrogen mineralization on a seasonally reconstructed
      food web operating on infrequent and irregular prey capture.

PMID- 19582166
TI  - Polyclonal B cell differentiation and loss of gastrointestinal tract germinal
      centers in the earliest stages of HIV-1 infection.
AB  - BACKGROUND: The antibody response to HIV-1 does not appear in the plasma until
      approximately 2-5 weeks after transmission, and neutralizing antibodies to
      autologous HIV-1 generally do not become detectable until 12 weeks or more after
      transmission. Moreover, levels of HIV-1-specific antibodies decline on
      antiretroviral treatment. The mechanisms of this delay in the appearance of anti
      HIV-1 antibodies and of their subsequent rapid decline are not known. While the
      effect of HIV-1 on depletion of gut CD4(+) T cells in acute HIV-1 infection is
      well described, we studied blood and tissue B cells soon after infection to
      determine the effect of early HIV-1 on these cells. METHODS AND FINDINGS: In
      human participants, we analyzed B cells in blood as early as 17 days after HIV-1
      infection, and in terminal ileum inductive and effector microenvironments
      beginning at 47 days after infection. We found that HIV-1 infection rapidly
      induced polyclonal activation and terminal differentiation of B cells in blood
      and in gut-associated lymphoid tissue (GALT) B cells. The specificities of
      antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI)
      included not only HIV-1-specific antibodies, but also influenza-specific and
      autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal
      B cell activation. Follicular damage or germinal center loss in terminal ileum
      Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis
      and follicular lysis. CONCLUSIONS: Early induction of polyclonal B cell
      differentiation, coupled with follicular damage and germinal center loss soon
      after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced
      antibody responses and the delay in plasma antibody responses to HIV-1. Please
      see later in the article for Editors' Summary.

PMID- 19582169
TI  - Multiple horizontal gene transfer events and domain fusions have created novel
      regulatory and metabolic networks in the oomycete genome.
AB  - Complex enzymes with multiple catalytic activities are hypothesized to have
      evolved from more primitive precursors. Global analysis of the Phytophthora sojae
      genome using conservative criteria for evaluation of complex proteins identified
      273 novel multifunctional proteins that were also conserved in P. ramorum. Each
      of these proteins contains combinations of protein motifs that are not present in
      bacterial, plant, animal, or fungal genomes. A subset of these proteins were also
      identified in the two diatom genomes, but the majority of these proteins have
      formed after the split between diatoms and oomycetes. Documentation of multiple
      cases of domain fusions that are common to both oomycetes and diatom genomes
      lends additional support for the hypothesis that oomycetes and diatoms are
      monophyletic. Bifunctional proteins that catalyze two steps in a metabolic
      pathway can be used to infer the interaction of orthologous proteins that exist
      as separate entities in other genomes. We postulated that the novel
      multifunctional proteins of oomycetes could function as potential Rosetta Stones
      to identify interacting proteins of conserved metabolic and regulatory networks
      in other eukaryotic genomes. However ortholog analysis of each domain within our
      set of 273 multifunctional proteins against 39 sequenced bacterial and eukaryotic
      genomes, identified only 18 candidate Rosetta Stone proteins. Thus the majority
      of multifunctional proteins are not Rosetta Stones, but they may nonetheless be
      useful in identifying novel metabolic and regulatory networks in oomycetes.
      Phylogenetic analysis of all the enzymes in three pathways with one or more novel
      multifunctional proteins was conducted to determine the probable origins of
      individual enzymes. These analyses revealed multiple examples of horizontal
      transfer from both bacterial genomes and the photosynthetic endosymbiont in the
      ancestral genome of Stramenopiles. The complexity of the phylogenetic origins of
      these metabolic pathways and the paucity of Rosetta Stones relative to the total
      number of multifunctional proteins suggests that the proteome of oomycetes has
      few features in common with other Kingdoms.

PMID- 19582168
TI  - TRPM8, a versatile channel in human sperm.
AB  - BACKGROUND: The transient receptor potential channel (TRP) family includes more
      than 30 proteins; they participate in various Ca(2+) dependent processes. TRPs
      are functionally diverse involving thermal, chemical and mechanical transducers
      which modulate the concentration of intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)
      triggers and/or regulates principal sperm functions during fertilization such as
      motility, capacitation and the acrosome reaction. Nevertheless, the presence of
      the TRPM subfamily in sperm has not been explored. PRINCIPAL FINDINGS: Here we
      document with RT-PCR, western blot and immunocitochemistry analysis the presence
      of TRPM8 in human sperm. We also examined the participation of this channel in
      sperm function using specific agonists (menthol and temperature) and antagonists
      (BCTC and capsazepine). Computer-aided sperm analysis revealed that menthol did
      not significantly alter human sperm motility. In contrast, menthol induced the
      acrosome reaction in human sperm. This induction was inhibited about 70% by
      capsazepine (20 microM) and 80% by BCTC (1.6 microM). Activation of TRPM8 either
      by temperature or menthol induced [Ca(2+)]i increases in human sperm measured by
      fluorescence in populations or individual sperm cells, effect that was also
      inhibited by capsazepine (20 microM) and BCTC (1.6 microM). However, the
      progesterone and ZP3-induced acrosome reaction was not inhibited by capsazepine
      or BCTC, suggesting that TRPM8 activation triggers this process by a different
      signaling pathway. CONCLUSIONS: This is the first report dealing with the
      presence of a thermo sensitive channel (TRPM8) in human sperm. This channel could
      be involved in cell signaling events such as thermotaxis or chemotaxis.

PMID- 19582171
TI  - Preoperative evaluation and preparation for anesthesia and surgery.
AB  - The ultimate goals of preoperative medical assessment are to reduce the patient's
      surgical and anesthetic perioperative morbidity or mortality, and to return him
      to desirable functioning as quickly as possible. It is imperative to realize that
      "perioperative" risk is multifactorial and a function of the preoperative medical
      condition of the patient, the invasiveness of the surgical procedure and the type
      of anesthetic administered. A history and physical examination, focusing on risk
      factors for cardiac and pulmonary complications and a determination of the
      patient's functional capacity, are essential to any preoperative evaluation.
      Laboratory investigations should be ordered only when indicated by the patient's
      medical status, drug therapy, or the nature of the proposed procedure and not on
      a routine basis. Persons without concomitant medical problems may need little
      more than a quick medical review. Those with comorbidity should be optimized for
      the procedure. Proper consultations with appropriate medical services should be
      obtained to improve the patient's health. These consultations should ideally not
      be done in a "last second" fashion. The preoperative preparation involves
      procedures that are implemented based on the nature of the expected operation as
      well as the findings of the diagnostic workup and the preoperative evaluation.

PMID- 19582170
TI  - Antihypertensive agents and renal transplantation.
AB  - Advances in the field of kidney transplantation have led to a significant
      increase in the life of renal allograft with 1-year graft survival rates of 93%
      to 99%. This increase in early graft survival has made it possible to observe the
      long-term morbidities that accompany renal transplantation. Studies correlating
      the reduction of arterial blood pressure with patient and graft survival as well
      as the risk of cardiovascular disease do not exist. The recommendations come from
      the general population and from comparative studies of hypertensive and
      normotensive kidney graft recipients. It is known that in the general population
      hypertension is a risk factor for chronic kidney disease but at the same time a
      risk factor for death, ischaemic heart disease, chronic heart failure and left
      ventricular hypertrophy. We must always have in mind that there are many
      similarities between a kidney graft recipient and a patient with chronic kidney
      disease. Renal transplant recipients represent a patient population with a very
      high risk for development of cardiovascular disease which has been identified as
      the leading cause of death in these patients. Of 18,482 deaths among renal
      allograft recipients, 38% had functioning renal allografts. Successful renal
      transplantation (Rt) can result in partial regression of left ventricular
      hypertrophy (LVH) if it is associated with hypertension (HTN) remission or if HTN
      is controlled by medications. Frequently post transplant HTN is associated with
      failure of LVH to regress. Transplant clinicians must choose antihypertensive
      agents that will provide their patients with maximum benefit from renal allograft
      and cardiovascular perspective. The target must always be long term patient and
      graft survival and acceptable quality of life. The antihypertensive drugs usually
      used after kidney transplantation are diuretics, calcium channel blockers,
      angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and
      beta-blockers. Most emphasis is given lately to ACEIs/ARBs and beta-blockers
      because of their cardioprotecive effect.

PMID- 19582172
TI  - Interventional nephrology: a new subspecialty of nephrology.
AB  - Interventional Nephrology is a new and emerging subspecialty of Nephrology that
      mainly deals with ultrasonography of kidneys and ultrasound-guided renal biopsy,
      insertion of peritoneal dialysis catheters, tunneled dialysis catheters as a
      vascular access for patients undergoing hemodialysis as well as percutaneous
      endovascular procedures performed to manage dysfunction of arteriovenous fistulas
      or grafts in end stage renal disease patients. Traditionally, these procedures
      have been delegated to a variety of specialists with resultant delays in
      diagnosis and initiation of therapy. To avoid the delays nephrologists have taken
      the initiative to perform these procedures themselves. Indeed, recent data have
      emphasized that nephrologists can safely and successfully perform these
      procedures with excellent results. The success of nephrologist's role in
      Interventional Nephrology insures the ideal management of renal patients with
      effectiveness, safety and lower cost for Public Health System. Certainly
      nephrologists must have adequate training and develop the necessary skills in the
      new fields as a prerequisite for the success of the concept.

PMID- 19582173
TI  - Use of amifostine in the treatment of recurrent solid tumours in children.
AB  - AIM: Preclinical and clinical evaluation of amifostine (AMI) administration in
      conjunction with systemic chemotherapy supports its role as a cytoprotective
      agent of normal tissues without loss of impairing the antitumour effectiveness of
      chemotherapeutic agents. Since only a limited number of clinical studies has been
      performed using AMI in paediatric pts with malignancies we investigated the
      protective effect of AMI against carboplatin-induced myelotoxicity and
      nephrotoxicity in a paediatric group of patients. MATERIAL AND RESULTS: AMI was
      administered in 18/28 paediatric patients with reccurent solid tumours along with
      ICE (ifosfamide, carboplatin, etoposide) chemotherapy. A significant (p<0.05)
      decrease in GFR was observed in the control group whereas it was maintained at
      pre-treatment levels in the AMI-treated group. Leukopenia and neutropenia were
      significantly (p<0.05) less in AMI-group. No protective effect of AMI was shown
      concerning thrombocytopenia. CONCLUSIONS: AMI was generally well tolerated at the
      dose of 740 mg/m2. Side effects including nausea, vomiting, hypotension, flushing
      and rigors were moderate and reversible and the interruption of infusion was
      never required.

PMID- 19582174
TI  - Angina pectoris and intensive intravenous iron treatment in hemodialysis
      patients.
AB  - BACKGROUND: Intravenous iron and erythropoietin are commonly used for the
      treatment of anemia in end stage renal disease (ESRD) patients. Even though i.v.
      iron is proven to be very effective, there is great concern regarding its
      possible toxic effects. The aim of our study was to evaluate the possible
      correlation between iron administration and the incidence of angina pectoris in
      hemodialysis patients. METHODS: The study sample consisted of 10 stable coronary
      heart disease patients, receiving chronic hemodialysis treatment. The patients
      followed consecutively three different i.v. iron dose regimens according to their
      needs. Their standard monthly laboratory measurements were correlated with the
      incidence of angina pectoris and i.v. iron treatment. RESULTS: Hematocrit,
      ferritin, serum iron and mean rhEPO dose were related to the total amount of
      administered iron. Angina pectoris was related to intensive iron treatment, age
      and platelet count. Total white blood cell count were related to hemodialysis
      duration, platelet count and serum triglycerides. CONCLUSION: It is suggested
      that the intensive intravenous iron treatment (300 mg/week) is associated with
      the increased incidence of angina pectoris in stable coronary heart disease
      patients receiving hemodialysis.

PMID- 19582175
TI  - Our experience in open rhinoplasty.
AB  - AIM: The last decade the external approach has gained enormous popularity in
      rhinoplastic surgery and it is a relatively new technique in Greece for the
      correction of functional and aesthetic problems of the nose. We introduce our
      experience in open rhinoplasty, we describe the operative technique, its
      advantages. MATERIAL-METHODS: In a period of two years (2003-2005), 98 patients
      underwent open rhinoplasty in our department. In 42 of them, breathing problems
      were existed in combination with nasal deformities. Eighty seven patients
      underwent septo/rhinoplasty under general anesthesia and the other 11 under local
      anesthesia. RESULTS: The postoperative course was uneventful, painless and
      without postoperative bleeding in all patients. Postoperative photo documentation
      was performed in all of them after 1, 3, 6, and 12 months. Only two patients
      needed to undergo revision surgery (the first patient due to "polly beak"
      deformity and the second one due to postoperative nasal valve stenosis). The scar
      of broken columella incision was invisible in all patents some weeks
      postoperatively. CONCLUSION: In open approach in Rhinoplasty, as provides a full
      exposure of the osseocartilaginous vault, it is much more easier to perform all
      the modern rhinoplasty techniques with sutures, biological and non biological
      materials, to modify the nasal tip deformities and asymmetries and to gain an
      aesthetic result balanced with the other facial components. Its disadvantages are
      minimal, that's why it becomes every day more popular all over the world.

PMID- 19582176
TI  - Inflammation and anaemia as predictors of cardiovascular mortality in
      hemodialysis patients.
AB  - BACKGROUND: Cardiovascular diseases are the most common causes of death among
      hemodialysis (HD) patients, yet the risk factors for these events have not been
      well established. Our study objective was to determine predictors of
      cardiovascular mortality, considering the non-traditional/disease-related and
      treatment-related/ cardiovascular risk factor in HD patients. MATERIAL AND
      METHODS: Disease-related cardiovascular risk factors, such as anaemia, calcium
      phosphate disorders, nutrition-inflammation and treatment/dialysis-related
      cardiovascular risk factors such as HD dose, using the index Kt/V were analyzed
      in 214 patients on HD. Mortality was monitored prospectively over a two year
      period. RESULTS: Fifty-three of the 214 HD patients died during the follow-up
      period and the main cause of death was cardiovascular events (56.6%), followed by
      infection/sepsis (26.4%). The patients who died were significantly older than
      those alive, had significantly lower serum levels of hemoglobin (Hb), albumin and
      Kt/V. Serum levels of calcium, C-reactive protein (CRP) and fibrinogen were
      significantly higher in patients who died during the follow-up period. Kaplan
      Meier analysis showed that the all cause and cardiovascular mortality was
      considerably higher in patients with Hb<110 g/l, albumin <40 g/l, CRP>8 mg/l and
      spKt/V<1.2 (log rank, p=0.000/p=0.000, p=0.000/ p=0.001, p=0.000/p=0.000,
      p=0.000/p=0.000), respectively. No difference in cardiovascular mortality was
      observed between the fibrinogen <4 g/l> levels. High CRP, low Hb levels and low
      spKt/V were significant predictors of all-cause mortality, but low albumin and
      high fibrinogen levels were not in the Cox proportional hazards analysis. When
      only cardiovascular mortality was entered into the Cox model, high CRP and low Hb
      levels were the only significant predictors for mortality. CONCLUSIONS: It can be
      concluded that, inflammation (elevated CRP) and anaemia (decreased Hb), were
      identified as significant independent non-traditional, disease-related
      cardiovascular risk factors that predict cardiovascular mortality in HD patients.

PMID- 19582177
TI  - Delayed interval delivery in twin pregnancy: a case report. We present a case of
      delayed interval delivery in twins.
AB  - We report a case of diamniotic, dichorionic pregnancy presented at 24 weeks with
      premature rupture of the first amnionic sac. Seven days later, premature labour
      and delivery of the first twin took place, with unfortunate outcome. The second
      twin was left in utero. The management included combination of tocolytics,
      antibiotics and cervical cerclage. Caesarean section was performed 48 days later,
      at 32 weeks and we delivered a live male infant, successfully.

PMID- 19582179
TI  - Epithelial ovarian cancer. Risk factors, screening and the role of prophylactic
      oophorectomy.
AB  - Epithelial ovarian cancer is the seventh most frequent cancer in European women.
      Many theories have been postulated regarding the pathogenesis of ovarian cancer.
      Risk factors are not well defined, with the exception of low parity and oral
      contraceptive use. Approximately 10% of ovarian cancer are hereditary, with BRCA1
      and BRCA2 explaining the majority (approximately 90%) of hereditary ovarian
      cancer cases. The lifetime risk varies between 15 and 66%, suggesting the
      existence of modifying genetic or environmental factors.Family history can be
      used to define women who are at increased risk of ovarian cancer. Individuals at
      high risk are those with a first degree relative (mother, father, sister,
      brother, daughter or son) affected by cancer. It must be noted that currently
      available tests do not attain the aforementioned high level of sensitivity.
      Evidence suggest that presymptomatic screening by grey scale ultrasound (with or
      without Doppler), CA125, pelvic examination, or combinations of these, are not
      effective in detecting tumors at an early stage. Women identified as being at
      high risk of ovarian cancer can be offered prophylactic oophorectomy. The
      decision whether or not to proceed to prophylactic oophorectomy is influenced by
      the fact that most women at increased risk of ovarian cancer are also at
      increased risk of breast cancer and there is evidence that oophorectomy reduces
      breast cancer in these cases.

PMID- 19582178
TI  - Assessment of airway inflammation with exhaled NO measurement.
AB  - Assessing airway inflammation is important for investigating the underlying
      mechanisms of many lung diseases, including asthma, chronic obstructive pulmonary
      disease (COPD), bronchiectasis, primary ciliary dyskinesia (PCD) and cystic
      fibrosis. A growing interest has recently directed toward non-invasive methods
      for the assessment of airway inflammation. Measurement of exhaled nitric oxide in
      exhaled air is an exciting innovative technique that gives new insights into the
      pathophysiology of lung disease and asthma in particular, with many potential
      clinical applications. Careful standardisation of measurement techniques has
      facilitated the use of this new measurement in paediatric respiratory medicine.
      Non-invasiveness and instantaneous results potentially make it a suitable
      instrument for use in children starting from the age of 4, with useful
      applications both in asthma diagnosis and monitoring.

PMID- 19582180
TI  - Pruritus in certain internal diseases.
AB  - In the past it was widely believed that pain and itching are transmitted by the
      same nerve pathway with the low intensity stimulation of unmyelinated polymodal C
      fibers resulting in sensation of pruritus whereas high intensity stimulation
      causing pain. In recent experiments however, stimulation of single unmyelinated C
      fibers led to the identification of two kinds of fibers. Stimulation of most of
      these fibers induces pain, whereas a small number of fibers provoke the sensation
      of itching. Pruritus is an unpleasant sensation, often accompanied by scratching.
      It may present due to a number of cutaneous diseases or internal disorders.
      Pruritus may be caused by some chemical substances as histamine, prostaglandins,
      proteases and substance P. This review describes the existence of pruritus in
      different internal disorders. It is quite important the reason of pruritus to be
      discovered, for the application of an adequate therapy.

PMID- 19582181
TI  - Hypertension and progression of nephropathy in diabetic and non-diabetic chronic
      kidney disease patients.
AB  - BACKGROUND: Hypertension is associated with more rapid progression of chronic
      kidney disease. Several studies have shown that treating hypertension in patients
      with chronic kidney disease and proteinuria may attenuate the decline in
      glomerular filtration rate. STUDY OBJECTIVE: The study evaluates the prevalence
      of hypertension and its association with chronic kidney disease progression in
      patients without and with diabetic nephropathy. METHODS: Patients with CKD stage
      2-4 were followed up by a nephrologist for 12-52 months. A total of 137 patients
      were included in the study, 70 with non-diabetic CKD and 67 with type 2 diabetes
      and diabetic nephropathy. Demographic and clinical parameters were recorded at
      initiation and during follow-up. Glomerular filtration rate was estimated by the
      Cockroft-Gault formula and progression of CKD by the slope of the estimated GFR
      decline. RESULTS: Out of 70 patients in the non-diabetic group, 34 were males,
      (mean age 50.37+/-12.2 years). Out of 67 diabetic patients, 30 were (males, mean
      age 57.8+/-8.4 years). 77% in the non-diabetic group had SBP above 140 mmHg. The
      higher SBP was associated with older age, (53.16+/-10.8 vs 40.9+/-12.2 years,
      p<0.0001). Diastolic blood pressure above 90 was present in 73%. Pulse pressure
      above 80 had 5.7% and was associated with older age (p<0.02). Progression of
      chronic kidney disease correlated inversely with age, and positively with
      diastolic blood pressure and proteinuria (p=0.005, p=0.019 and p=0.02
      respectively). Multiple regression analysis showed that only younger age and
      higher proteinuria were predictive for chronic kidney disease progression
      (p=0.00002). 6% of pts in the diabetic group had SBP below 140, 19% between 140
      and 160, and 75% above 160 mmHg. Diastolic blood pressure below 80 had only 6% of
      patients, between 80 and 90 had 37% and above 90 mmHg had 57%. Pulse pressure
      below 80 mmHg had 55% and it was correlated positively with age, p=0.009.
      Progression of chronic kidney disease in the diabetic group correlated positively
      with mean arterial pressure, systolic blood pressure and proteinuria, (p=0.017,
      0.036 and 0.000000 respectively) and inversely with age (p=0.0003). Multiple
      regression analysis showed that proteinuria, age and SBP were the only predictors
      for chronic kidney disease progression in diabetics. CONCLUSION: Isolated
      systolic hypertension predominates the older age groups, proteinuria and age
      significantly correlate with GFR decline in both groups, and SBP is associated
      with more rapid progression of CKD in the diabetic patients.

PMID- 19582182
TI  - Preoperative evaluation, surgical procedure, follow up and results of 150
      cochlear implantations.
AB  - BACKGROUND: The cochlear implantation is among the most important achievements of
      medicine and biotechnology in the last 20 years, because it allows individuals
      who had never heard or had lost their hearing to perceive sound and improve their
      quality of life. Selection criteria for candidates are strict and are evaluated
      in each individual by a scientific committee specially trained for implantations
      which includes Ear Nose and Throat (ENT) surgeon, audiologist, psychiatrist and
      speech therapist. PATIENTS AND METHODS: In our department, the first cochlear
      implantation was performed in 1995. During the last ten years more than 250
      individuals have been evaluated due to profound hearing loss and 170 of them were
      found to be suitable candidates for cochlear implantation. One hundred and fifty
      (150) have already been operated and most of them are children with congenital
      hearing loss. No major or permanent complications were recorded in any of our 150
      patients. Activation and fitting/mapping of the cochlear implant is initiated
      three weeks post-operatively. Regular follow-up and mapping of the implant are
      held, more frequently in children, along with specialized speech therapy. Each
      new mapping is evaluated according to the record of the patient with regard to
      the acoustic perception of sounds and speech and the discrimination of individual
      elements of phonation based on a protocol that we have created for the needs of
      Greek language. RESULTS: Speech discrimination (AHEPA Hospital protocol), before
      the Implantation, at the activation of the cochlear implant and till 4 years of
      the follow-up showed that in our patients, we obtained better and faster results
      in post-speech acquisition adults with recent or chronic deafness and in children
      with congenital deafness operated before the 5th year of age, who underwent
      special preoperative speech therapy programme, fact which is in agreement with
      current literature. Patient satisfaction evaluated by "Sanders" psychometrics
      tests, was achieved in accordance to pre-operative expectations. CONCLUSIONS: In
      our patients, we observed better and faster results in children with congenital
      deafness operated before the third year of age, in post-speech acquisition adults
      with recent deafness and in post-speech acquisition adults with chronic deafness
      but with auditory memory reserve.

PMID- 19582183
TI  - Efficacy of captopril therapy in cystinuria lithiasis. A case report.
AB  - We present a 7-year old girl with severe urolithiasis due to cystinouria. Medical
      treatment after the surgical procedures was initiated with intensive hydration,
      urine alkalinisation and captopril. We discuss the therapeutic efficacy of
      captopril in resolving lithiasis as well as in preventing new stone formation.

PMID- 19582184
TI  - Management of a giant ruptured hepatocellular adenoma. Report of a case.
AB  - This report describes a rare case of a young woman with massive intra-abdominal
      bleeding due to a giant ruptured hepatocellular adenoma. The patient had never
      used oral contraceptive pills and she was urgently operated for haemorrhage
      control in another hospital where the left hepatic artery was also ligated. After
      haemodynamic stabilization in the ICU and because of a complicated postoperative
      course (signs of intraabdominal sepsis) she was transferred to our hospital and a
      left lobectomy was performed. We present the case and comment on the preferred
      treatment modalities of hepatocellular adenomas.

PMID- 19582185
TI  - Trichoblastic carcinoma of the pinna. A rare case.
AB  - Adnexal tumors of the hair follicle can be regarded as lesions that show similar
      differentiation to one or more portions of the hair follicle. Trichoblastic
      carcinoma is a rare malignant adnexal tumor, which usually occurs on the scalp.
      There have been reported cases with regional lymph node metastasis. We report a
      case of a 65 years old man with a painless irregular mass of the posterior
      surface of the right pinna, which was slowly growing over a 5-year period. He had
      a history of a similar lesion on the same site, which was removed 8 years before
      he presented to us. We excised the lesion and the defect was covered with an
      advancing flap. Because of the histology result the patient was re-operated and
      reviewed for over 3 years and there wasn't any sign of recurrence.

PMID- 19582186
TI  - Human and ape: the legend, the history and the DNA.
AB  - A vast amount of papers is published every year about species evolution, the most
      interesting being those recently published in the journal "Nature", concerning
      the human-ape relationship. The results and the new theories generated from this
      research are sometimes astonishing, raising not only biological, but also social,
      religious and cultural questions. One of the new questions concerns the role of
      species interbreeding as a means of evolution. In the subject of species
      interbreeding between human and ape we found some interesting historical and
      mythical information that sort of back-up this theory of interbreeding, with a
      historical and cultural side view.

PMID- 19582187
TI  - Leptin as a cardiovascular risk factor.
AB  - The role of leptin in humans is not yet precisely established. Nevertheless there
      is increasing evidence revealing that this molecule is involved in the
      pathogenesis of atherosclerosis as an independent risk factor. From another point
      of view, however, leptin is already related to known traditional risk factors for
      accelerated atherogenesis, like obesity. We herein provide the experimental and
      clinical data concerning the association between leptin and atherosclerotic
      disease. Vascular stiffness and calcification, immune response regulation,
      fibrinolysis, and oxidative stress, are the main fields to be investigated in
      relation to leptin in the present study. Additionally the description of the main
      characteristics of leptin and its receptors is included in the introduction of
      this article, whereas in the end the main clinical data suggesting that this
      molecule represents an interesting risk factor for atherosclerotic disease are
      provided.

PMID- 19582189
TI  - Anesthesia for the elderly.
AB  - Aging is a universal and progressive physiological phenomenon clinically
      characterized by degenerative changes in both the structure and the functional
      capacity of organs and tissues. In general, geriatric patients are more sensitive
      to anesthetic agents. Less medication is usually required to achieve a desired
      clinical effect, and drug effect is often prolonged. The most important outcome
      and overall objective of perioperative care of geriatric population, is to speed
      recovery and avoid functional decline. An important principle must be kept in
      mind when dealing with an elderly patient: Aging involves a progressive loss of
      functional reserve in all organ systems, to variable extent. Compensation for age
      related changes is usually adequate, but limitation of physiological reserve is
      evident during times of stress such as the perioperative period.

PMID- 19582188
TI  - The management of hypertension in hemodialysis and CAPD patients.
AB  - Patients with chronic kidney disease progress to end stage renal disease and
      about 86% are diagnosed hypertensives. Hypertension is a risk factor for
      cardiovascular disease which is the main cause of morbidity and mortality in the
      dialysis population. Pre and post-dialysis blood pressure values of <140/90 mmHg
      are recommended as the optimal blood pressure. The extra-cellular volume (ECV)
      expansion is the main pathophysiological determinant of hypertension in dialysis
      patients. The efforts should be made to correctly estimate and achieve the
      patients dry body weigh and to limit dietary sodium intake. Angiotensin II
      receptor antagonists, beta blockers and calcium channel blockers are recommended
      as first choice drugs. Beta blockers and calcium channel blockers have been
      associated with reduced cardiovascular mortality and give their protective
      effects in patients at high risk. Antihypertensive drug therapies can effectively
      reduce blood pressure and are needed by the vast majority of hemodialysis
      patients.

PMID- 19582190
TI  - The role of apoptosis and current therapeutic challenges in myelodysplastic
      syndromes.
AB  - The myelodysplastic syndromes (MDS) remain challenging to the clinician in terms
      of diagnosis and management. The diagnosis is essentially one of exclusion in
      first ruling out other disorders that can also cause peripheral blood/bone marrow
      cell dysplasia and cytopenias. Recent studies implicate extensive apoptosis as
      the explanation of the paradoxical observation of marrow hyperplasia, but
      peripheral blood cytopenia. The clonal nature of MDS places it also at continual
      risk for transformation to acute leukemia. Predicting overall survival as well as
      the risk of acute myeloid leukaemia (AML) transformation has been improved by the
      development of the International Prognostic Scoring System (IPSS). Management of
      MDS can now be based on the patients respective prognostic subgrouping. Low-risk
      patients should be considered for hematopoietic growth factor singly or in
      combination, while high-risk patients should be offered AML-induction therapy or
      novel therapeutic agents. Common complications are neutropenias with recurrent
      infections and red cell transfusion dependence. Future advances upon
      understanding the molecular details of the MDS clone should ultimately improve
      the care of patients with MDS.

PMID- 19582191
TI  - Hearing aids: quality of life and socio-economic aspects.
AB  - OBJECTIVE: Hearing loss can significantly impair patient's quality of life,
      affecting communicative behavior, emotional and social function. This study
      assesses the impact of hearing aids on the quality of life of patients in a rural
      area and its correlation with socio-economic factors. MATERIALS-METHODS: Thirty
      patients (18 male, 12 female), with bilateral sensorineural hearing loss of
      variable etiology, using hearing aid for at least five years, were enrolled in
      this study. Mean age of subjects was 74 years. This study used the Glasgow
      Benefit Inventory (GBI) to quantify the changes in quality of life. Patients were
      divided in above and below criterion group. The criterion used was the median of
      the air contraction threshold improvement. The binaural use and the type of
      hearing aids were recorded and correlated with the type of social security
      service of patients. RESULTS: Eighty per cent of patients reported significant
      benefit from the hearing aid use. The majority of patients (90%) used one hearing
      aid (mean GBI total score 35) and only 10% had binaural hearing aid (mean GBI
      total score 45). The majority of patients used analog hearing aid (56.5%) while
      43.5% used digital hearing aid. Interestingly, it was found that patients did not
      attend appointments for hearing aids maintenance with a mean follow up of 2.5
      years. CONCLUSION: This study demonstrates a trend of better quality of life for
      patients with bilateral hearing loss and binaural hearing aid use. The type of
      hearing aid is related to the funding from their social security service.
      Therefore more patients are using analog hearing aids, as they are less expensive
      than the digital hearing aids.

PMID- 19582192
TI  - Contributions of signal analysis to the interpretation of spirometry.
AB  - AIM: Chronic Obstructive Pulmonary Disease (COPD) is taking on catastrophic
      proportions. However, there is still a need for more objective and quantitative
      methods for its diagnosis and stratification. The present study explores the
      effectiveness of signal analysis methodologies as the means to increase the
      effectiveness of spirometry in diagnosing and stratifying COPD. METHODS: Since
      expiratory flow at the mouth results from converging airflows, it is possible to
      use signal analysis to identify changes in the characteristics of airflow along
      the respiratory tree. This was achieved by non-invasively identifying alterations
      in the frequency spectrum of the Forced Expiratory Flow (FEF) curve of 108
      patients (49 men and 59 women, 12-75 yrs of age) presenting with (a) clinically
      and spirometrically normal respiratory profile, (b) COPD, (c) restrictive lung
      disease and (d) interstitial fibrosis. Fundamental to the study design was the
      notion that the characteristics of the expiratory output of the respiratory
      system are determined by the bronchial tree and the upper respiratory tract.
      RESULTS: A number of quantitative measures for the power spectrum of the FEF
      curve were identified, which permit the definition of specific rules and allow
      for the accurate classification of, at least, the basic types of respiratory
      disease. CONCLUSIONS: (a) It is for the first time that airflow resonances are
      identified in the sub-audible (<20 Hz) range of the power spectrum of the FEF
      curve. (b) COPD patients present with FEF curves which have different power
      spectral characteristics from those of healthy individuals (p<0.01), at
      frequencies lower than 3.66 Hz. (c) In COPD, in restrictive lung disease and in
      interstitial fibrosis, the lower resonant frequencies of the spectrum of the FEF
      curve predominate.

PMID- 19582193
TI  - Treatment of intravenous drug users with chronic hepatitis C: treatment response,
      compliance and side effects.
AB  - BACKGROUND: Although intravenous drug users (IVDUs) comprise the majority of
      patients with chronic hepatitis C, most of them are excluded from treatment
      because of concerns about adherence to treatment and side effects. MATERIAL AND
      METHODS: In this study we retrospectively evaluated safety, compliance to
      treatment and efficacy of treatment in IVDUs with HCV infection in 163 former
      IVDUs with chronic hepatitis C, who were not in methadone substitution and were
      attending our clinics the period 1997-2004. All subjects were HCVRNA (+), had ALT
      levels>x1.5 UNL and were treated for their HCV infection. Treatment consisted of
      three different regimens: IFN-alpha monotherapy (39.8%), IFN-alpha/ribavirin
      combination therapy (30.1%) and pegylated IFN-alpha/ribavirin combination
      therapy. RESULTS: Eighty seven over 163 patients (53.3%) discontinued treatment
      early due to drug abuse relapse (62%), side effects (32.1%, 10% psychiatric) and
      5,7% for other reasons. Eighty precent of those who discontinued treatment had
      pre-treatment drug abstinence<or=9 months. Seventy over 76 patients who completed
      therapy had an end-of-treatment virologic response (ETR, 92%). Fifty four over 76
      patients showed sustained virologic response (SVR, 71.05%). ETR and SVR were
      significantly higher in both combination therapies compared to IFN-alpha
      monotherapy. The most prevalent HCV genotype was 3 (65%) and mild histological
      lesions were detected in the majority of subjects. CONCLUSIONS: Our findings show
      that treatment for chronic hepatitis C was reasonably safe and sufficiently
      effective in our group of non methadone-substituted IVDUs, despite the fact that
      more than half of them discontinued treatment early and many relapsed to drug
      abuse. We suggest that the optimal duration of pretreatment abstinence from drug
      abuse should be >/= 9 months.

PMID- 19582194
TI  - Changes of serum bone markers in CAPD and hemodialysis patients.
AB  - BACKGROUND: A non-invasive method for evaluation of high-turnover and low
      turnover bone diseases is the measurement of certain important serum bone markers
      such as osteocalcin, procolagen-I-propeptide, dioxypiridinoline, hydroxyproline
      and alkaline phosphatase. Renal osteodystrophy (ROD) in pre-dialysis and dialysis
      patients, is manifested in 3 forms: high-turnover ROD, related to secondary
      hyperparathyroidism; low-turnover ROD and mixed ROD. MATERIAL AND METHODS: Serum
      levels of intact parathyroid hormone (iPTH), osteocalcin (OC), procolagen-I
      propeptide (PIPC) and dioxypiridinoline (DYP) were measured in 20 patients on
      hemodialysis (HD) and 20 patients on continuous ambulatory peritoneal dialysis
      (CAPD) to assess the prevalence of ROD type in the HD and CAPD groups. RESULTS:
      We found lower mean levels of all bone markers in CAPD patients, (iPTH: 219+/-235
      vs. 428+/-285 pg/ml; p<0.01; OC 10.2+/-7.5 vs. 21.3+/-7.2 ng/ml; p<0.01; PIPC
      111+/-57.3 vs. 218+/-62.4 ng/ml; p<0.01; DYP 7.3+/-6.4 vs. 55.2+/-23.3nm/l;
      p<0.001; AP 164+/-66 vs. 325+/-188 U/l; p<0.01) and lower than normal in 11 of
      them and higher than normal PTH, AP and some of the other serum markers (PICP;
      DYP) in 14 HD patients. CONCLUSIONS: The lower levels of the investigated serum
      bone markers in CAPD patients suggest that low-turnover ROD prevails in these
      patients than in HD pts.

PMID- 19582195
TI  - Results of active cycle of breathing techniques and conventional physiotherapy in
      mucociliary clearance in children with cystic fibrosis.
AB  - AIM: The aim of the present study is the comparison of the results of the
      appliance of two methods of respiratory physiotherapy; the active cycle of
      breathing techniques in drainage positions and the conventional physiotherapy,
      regarding their effects on mucociliary clearance in patients with cystic
      fibrosis. MATERIAL-METHODS: Thirty-five children teenagers and adults with cystic
      fibrosis, 8-20 years of age, with mean Schwachman score 78,49 took part in the
      research. All patients had regular physiotherapeutic control and applied
      systematically physiotherapy. The same children received two methods of
      respiratory physiotherapy in a 3-month random order, when they came at the
      outpatients' department of the hospital for their regular check-up. RESULTS: The
      comparison of the results of the two methods did not show statistical significant
      difference in sputum quantity, whereas statistical significant difference was
      noticed in sputum quality after the application of active cycle of breathing
      techniques. CONCLUSIONS: The application of the active cycle of breathing
      techniques contributes effectively in the sputum expectoration from the
      peripheral bronchopulmonary segments and enhances the mucociliary clearance in
      children with cystic fibrosis.

PMID- 19582196
TI  - Homocystein and carotid atherosclerosis in chronic renal failure.
AB  - BACKGROUND: Since total homocysteine (Hcy) is markedly elevated in patients with
      chronic renal failure (CRF), it has been presented as potential factor
      contributing to the high risk of cardiovascular disease (CVD) in CRF. The aim of
      the study was to examine the significance of elevated Hcy and other
      cardiovascular risk factors for carotid atherosclerosis in patients with CRF.
      MATERIAL AND METHODS: Fifty six patients 16-M, 40-F, average age 58+/-14.55,
      creatinine clearance 39.19+/-10.11 ml/min were examined. In addition, 20 control
      healthy subjects were examined. The association of Hcy levels and classic risk
      factors for atherosclerosis with common carotid intima-media thickness (IMT) was
      examined. B-mode ultrasound measurement of carotid IMT was performed in 56
      hypertensive pts with CRF (glomerular filtration rate>20 ml/min and <90 ml/min),
      44 hypertensive pts with normal renal function and 20 healthy volunteers. The
      mean duration of hypertension was 145.12 years. RESULTS: IMT in all examined
      hypertensive pts was increased above normal clinical value and significantly
      higher then in healthy controls (0.75+/-0.006/0.60+/-0.1, p<0.001). The carotid
      IMT was similar between hypertensive pts with CRF and hypertensive pts with
      normal renal function (0.74+/-0.1/0.76 +/-0.1, p>0.05). Significant predictors
      for IMT were age (r=0.358, p<0.04), duration of hypertension (r=0.395, p=0.023),
      diabetes duration (r=0.343, p<0.02), as well as duration of CRF (r=0.324,
      p<0.006). There was a negative correlation between IMT and glomerular filtration
      rate assessed by creatinine clearance (r=-0.303, p<0.003). Renal function,
      described by creatinine clearance was the strongest determinant for Hcy levels
      (r=-0.332, p<0.008). Increased IMT was estimated in pts with CRF compared to
      healthy controls (0.74+/-0.10 vs 0.59+/-0.10, p<0.001). We found association
      between Hcy and carotid IMT ( r=0.344, p<0.015). No consistent association was
      found between IMT and other specific for CRF cardiovascular risk factors.
      CONCLUSION: The study suggests that patients with mild renal failure have
      increased IMT of the common carotid artery and that elevated plasma Hcy level in
      CRF is associated with carotid intima- media thickening.

PMID- 19582197
TI  - Adamantiades-Behcet disease (ABD) in northern Greece patients: experience from a
      single center.
AB  - OBJECTIVE-METHODS: Adamantiades-Behcet disease (ABD) is a multi-systemic
      vasculitis of unknown origin, with a characteristic geographic distribution, that
      affects vessels of all kinds and sizes and is characterized by recurrent mucosal,
      skin and ocular lesions. In the present study, a series of 36 patients from
      Northern Greece is analyzed retrospectively in regard to the epidemiological,
      clinical and immunological parameters. RESULTS: All patients had recurrent oral
      ulcerations (36/36, 100%), while 23/36 (63.9%) experienced genital ulcerations
      and 22/36 (61.1%) developed ocular disease. Skin manifestations were observed in
      23/36 patients (63.9%) and pathergy test was found positive in 14/36 patients
      (38.9%). Other manifestations included central nervous system involvement,
      recurrent genitourinary inflammations, arthralgias and superficial
      thrombophlebitis. Laboratory findings were not specific, partly reflecting the
      severity of inflammation. Ocular disease was more often observed in HLA-B51 (+)
      patients (20/31, 64.5%) than in HLA-B51 (-) patients. Standard of care (SOC)
      treatment consisted of cyclosporine A, azathioprine, methylprednisolone and
      aspirin, whereas refractory disease was treated with intravenous pulses of
      methylprednisolone and cyclophosphamide. Occasionally, anti-TNF agents
      (infliximab) were applied to treat refractory ocular disease. CONCLUSION: The
      findings of the present study come in agreement with those reported for other
      Mediterranean series. HLA-B51 seems to predispose to more severe disease, while
      early therapeutic intervention is beneficial for these patients.

PMID- 19582198
TI  - Prevalence of musculoskeletal disorders in patients with type 2 diabetes
      mellitus: a pilot study.
AB  - BACKGROUND: Diabetes mellitus is associated with a variety of musculoskeletal
      disorders. The prevalence of connective tissue disorders in these patients has
      increased in the recent years affecting significantly their quality of life.
      METHODS-RESULTS: We conducted a pilot study including 208 sequentially selected
      patients with type 2 diabetes mellitus regularly followed-up at the Diabetes
      Center of the Hippokration University Hospital. Among the diabetic patients who
      were screened according to the Short Musculoskeletal Function Assessment
      Questionnaire for musculoskeletal symptoms and findings, 82.6% were found to
      exhibit musculoskeletal abnormalities, mainly of the degenerative,
      noninflammatory type. CONCLUSIONS: Musculoskeletal disorders are a common finding
      among patients with type 2 diabetes. Obesity and accumulation of abnormally
      glycosylated byproducts have been proposed as potential pathogenetic mediators of
      these connective tissue abnormalities. Of particular interest is, however, the
      common association of osteoarthritis, involving even non-weight bearing joints in
      patients with type 2 diabetes, indicating a common pathophysiologic mechanism
      connecting these two clinical conditions.

PMID- 19582199
TI  - Intraperitoneal pseudocyst formation: complication of fungal peritonitis in
      continuous ambulatory peritoneal dialysis.
AB  - A 14-year-old girl, with end-stage renal disease on continuous ambulatory
      peritoneal dialysis (CAPD) the last 4 years, after an episode of Candida albicans
      was switched to hemodialysis. One month later she came back because of a palpable
      painful abdominal mass and abdominal distention. Computed tomography (CT) and
      ultrasound examination demonstrated a demarkated fluid collection in the lower
      abdomen and pelvis. The cyst was drained percutaneously and the culture disclosed
      candida albicans which was treated with fluconasole. Two months later, the girl
      was admitted again with the same symptoms. An investigative laparotomy was
      undergone and the cyst was drained again. Fluid cultures were negative. CT
      abdomen examination six months later was negative for cyst relapse. In
      conclusion, intraperitoneal pseudocyst is a serious complication of CAPD.
      Surgical intervention may be preferable to percutaneous drainage.

PMID- 19582200
TI  - A critique on the possible protective role of Helicobacter pylori infection in
      childhood asthma.

PMID- 19582201
TI  - Male infertility and varicocele: myths and reality.
AB  - Varicocele is among the most common causes of male infertility. It is also one of
      the most controversial issues in the field of Andrology, especially regarding
      why, when and to whom varicocelectomy should be applied. Many experts believe
      that the surgical repair of varicocele should be applied only in a meticulously
      selected group of infertile men, although there are no generally accepted
      criteria. Up to now, the only confirmed prognostic factor for achievement of
      pregnancy after varicocelectomy is the age of the female partner. Given the wide
      application of intra-cytoplasmic sperm injection (ICSI) during the last few
      years, the modern research approaches should compare the benefits of
      varicocelectomy and ICSI, taking under consideration both the efficacy and the
      cost-effectiveness of the methods.

PMID- 19582202
TI  - Microalbuminuria, is it so important?
AB  - Microalbuminuria (defined as urinary albumin excretion of 30-300 mg/day, or 20
      200 microg/min) is an earlier sign of vascular damage. It is a marker of general
      vascular dysfunction and nowadays is considered a predictor of worse outcomes for
      both kidney and heart patients. There is a significant correlation between blood
      pressure and microalbuminuria. Even high normal blood pressure is associated with
      significant higher frequency of microalbuminuria and this way may be a biomarker
      of increased cardiovascular risk. Microalbuminuria could be taken also, as an
      indicator of insulin resistance and of the increased renal and cardiovascular
      risk associated with metabolic syndrome. Renal involvement is a pivotal
      development in diabetes and microalbuminuria is generally the first clinical sign
      of renal dysfunction in diabetics. It is demonstrated that cardiovascular and
      renal risk is elevated even in the high normal range of microalbuminuria (below
      30 mg/day). There is no doubt that therapies that prevent or delay the
      development of microalbuminuria and all measures that reduce it, may help to
      prevent or delay end organ damage.

PMID- 19582203
TI  - The proteins and the mechanisms of apoptosis: a mini-review of the fundamentals.
AB  - Apoptosis or programmed cell death is a physiological mechanism, characterized by
      specific morphological and biochemical changes such as cell shrinkage, chromatin
      condensation, protein cleavage, DNA breakdown and phagocytosis. Apoptosis is a
      significant contributor to the morphologic and functional development of
      multicellular organisms. It is also involved in the pathogenesis of several
      diseases including degenerative diseases of the central nervous system (CNS) like
      Alzheimer's disease or Parkinson's disease, cancer and immune system dysfunction.
      There are many factors, mainly proteins, which are involved in the activation,
      regulation and execution of related events. A fairly detailed outline of
      apoptotic mechanisms has also started to emerge and to be verified. In this
      short, focused mini-review, we attempt to outline current evidence regarding the
      mechanisms and the regulation of apoptosis.

PMID- 19582204
TI  - Blood pressure control and cardiovascular risk reduction.
AB  - The ultimate goal of antihypertensive therapy is cardiovascular risk reduction.
      As lowering blood pressure per se reduces risk for myocardial infarction only by
      20%-25%, it is obvious that a better protection is needed. An optimal strategy to
      reduce risk in hypertensives may include lifestyle modification, promotion of
      adherence to therapy, early and aggressive target levels achievement by
      appropriate drug choice. Clinical trial data suggest that RAAS blockers can
      reduce the risk at least partly independently of BP lowering. In addition, as
      hypertension is associated with a constellation of other risk factors, the global
      risk reduction is nowadays going to become the gold standard in therapy. The most
      common and important coexisting risk factor is hypercholesterolemia. This is not
      simply a co-existence but there is an independent and causal relationship between
      lipids and hypertension and there is a physiologic rationale and evidence for
      statins use especially in patients with complicated hypertension or in patients
      with more than two risk factors. So, whilst blood pressure lowering is
      undoubtedly beneficial, we have to focus on the global cardiovascular risk. We
      must go beyond blood pressure and the most effective way to go "beyond BP" is to
      add a statin.

PMID- 19582205
TI  - Is the Y chromosome all that is required for sex determination?
AB  - The gender identity of a person is the final result of genetic, hormonal and
      morphologic sex. Over a long period sex determination, and, specifically, male
      sex determination, has been correlated to the presence of the Y chromosome, which
      in turn has been the karyotype signal of the testes. However, research has
      provided data to convince that this theory is only part of the truth. In addition
      to the Y chromosome, a multitude of other genes influence sex determination and
      are able to cause male to female sex-reversal and vice versa. It is of great
      interest that these genes are located in more than one autosomal chromosomes or
      even in the X chromosome. It has become obvious that sex determination, according
      to the genetic sex, is a complicated matter that not only requires the presence
      of Y chromosome. This fact triggered extensive research of the Y chromosome and
      led to great insight into its structure, origin, evolution and eventual fate in
      humans.

PMID- 19582206
TI  - The kinin system--bradykinin: biological effects and clinical implications.
      Multiple role of the kinin system--bradykinin.
AB  - The present review article regarding the kinin system-bradykinin is dealing with
      the biological effects of the abovementioned entity mediated by specific B1 and
      B2 receptors as well as with its clinical implications known nowadays. The
      activation of the kinin system-bradykinin is particularly important in blood
      pressure regulation and in inflammatory reactions, through bradykinin ability to
      elevate vascular permeability and to cause vasodilatation in some arteries and
      veins. Recent data on bradykinin formation and release, synergy with ligands,
      receptors for bradykinin as well as on bradykinin participation in the
      mitogenesis process, are given in detail. Therapeutic potentials and future
      applications in many clinical situations including respiratory allergic
      reactions, septic shock, hypertension and its treatment, hypotensive transfusion
      reactions, heart diseases, pancreatitis, hereditary and acquired angioedema,
      Alzheimer disease and liver cirrhosis with ascites, are discussed in brief. Its
      role as a neuromediator, regulator of several vascular and renal functions, and
      its participation in signaling pathways, is also discussed in some detail.

PMID- 19582207
TI  - Rhabdomyolysis updated.
AB  - Rhabdomyolysis constitutes a common cause of acute renal failure and presents
      paramount interest. A large variety of causes with different pathogenetic
      mechanisms can involve skeletal muscles resulting in rhabdomyolysis with or
      without acute renal failure. Crush syndrome, one of the most common causes of
      rhabdomyolysis presents increased clinical interest, particularly in areas often
      involved by earthquakes, such as Greece and Turkey. Drug abusers are another
      sensitive group of young patients prone to rhabdomyolysis, which attracts the
      clinical interest of a variety of medical specialties. We herein review the
      evidence extracted from updated literature concerning the data related to
      pathogenetic mechanisms and pathophysiology as well as the management of this
      interesting syndrome.

PMID- 19582208
TI  - Investigation of the relationship between allergic rhinitis and personality
      traits using semeiometry.
AB  - Mind-body interactions have been well recognized and are extendedly studied in
      the medical literature. There is evidence that the mind and body communicate with
      each other in a multidirectional flow of information by means of hormones,
      neurotransmitters/neuropeptides, cytokines, and semaphorines. There are
      consistent and convincing reports of links between stress and disease onset and
      progression, e.g. asthma. Growing evidence in the field of psychoneuroimmunology
      contributes to the understanding of the mechanisms by which stressful events
      affect physical health. The psychoneuroendocrine system can influence the immune
      response and thereby the capacity of the organism to cope with illness, and the
      immune system can have an impact on neuroendocrine function. Such cross-talk
      among systems is dependent upon feedback loops working to maintain homeostatic
      equilibrium. The immune system is capable of producing factors, which serve to
      integrate immune-neuroendocrine circuits with immunoregulatory and metabolic
      consequences for the organism. The interaction of the immune, nervous and
      endocrine system may drive an individual to a well recognized biological
      hypersensitivity and the creation of allergic symptoms (allergic rhinitis,
      asthma, atopic dermatitis, etc), followed by distinct behavioural patterns
      characterized as affective hypersensitivity. Semeiometry is a proper tool for
      large scale investigation of the psychological profile of patients with allergic
      rhinitis. Statistical analysis of semeiometry questionnaires processed by Greek
      adult patients in Crete island during 2005, showed that there is relation between
      occupation and allergy. Housewives, public services employees and private
      employees appear to be allergic in significantly higher percentage than others.
      With semeiometry we can find evidence of the bi-directional immunoendocrine-
      nervous system interactions in patients with allergic rhinitis.

PMID- 19582209
TI  - L-arginine supplementation does not affect chemically induced carcinogenesis and
      tumor growth in BALB-c mice.
AB  - T-cell zeta-chain downregulation is common in various types of cancer and it is
      proposed as a mechanism of cancer immunosubversion. L-arginine consumption by
      arginase rich suppressor myeloid cells has been incriminated. The effect of L
      arginine supplementation on chemically induced carcinogenesis and tumor growth in
      mice was evaluated. METHODS: Eight-week old female BALB-c mice were used. Ten
      mice were injected i.m. with 0.6 mg methylcholanthrene (MCA) once. Ten mice were
      injected with MCA once and were receiving L-arginine supplementation (5% in
      animal drinking water) continuously during the study. Mice with cancer were
      sacrificed 12 weeks after. RESULTS: From the 10 MCA injected mice 6 developed
      sarcoma. From the 10 MCA injected mice that were receiving L-arginine
      supplementation 7 developed sarcoma. L-arginine supplementation did not affect
      MCA induced carcinogenesis (p=1.0, Fisher's exact test). The weight of tumors was
      not different between the tumors derived from mice that were or were not
      receiving L-arginine supplementation (1088.3+/-590.2 mg vs. 969.6+/-608.1 mg
      respectively, p=0.729, unpaired t-test). CONCLUSION: L-arginine supplementation
      does not affect chemically induced carcinogenesis and tumor growth in BALB-c
      mice. Although zeta-chain downregulation could be a mechanism of cancer
      immunosubversion there are enough other cancer immunosubversion mechanisms that
      were not overwhelmed by L-arginine supplementation. Additionally, except cancer
      immunosubversion, cancer immunoselection is another, possibly more significant,
      mechanism of tumor escape from immunosurveillance.

PMID- 19582211
TI  - Gitelman's syndrome (familial hypokalemia-hypomagnesemia).
AB  - Gitelman's syndrome (GS) is a heritable renal disorder characterized by
      hypomagnesemia, hypokalemia and hypocalciuria, and is distinct from Bartter's
      syndrome (BS). As compared to those with BS, patients with GS present at an older
      age, and they have a milder clinical picture, normal or slightly decreased
      concentrating urine ability, reduced urinary excretion of calcium, and
      permanently decreased serum magnesium level. GS is caused by defective NaCl
      transport in the distal convoluted tubule, and is linked to the gene encoding the
      thiazide sensitive Na-Cl-cotransporter located on chromosome 16q. Patients with
      BS, on the other hand, have mutations in the transporters in the thick ascending
      loop of Henle (NKCC2, ROMK, and C1C-Kb). Treatment of GS consists of magnesium
      salt replacement. Long term prognosis in terms of maintaining growth, preserving
      renal function and life expectancy is excellent.

PMID- 19582210
TI  - Is pepsin detected in the saliva of patients who experience pharyngeal reflux?
AB  - OBJECTIVES: To investigate if pepsin is detected, with an activity assay, in the
      saliva of patients with a clinical diagnosis of laryngopharyngeal reflux (LPR)
      and can therefore be used as a diagnostic marker of laryngopharyngeal reflux.
      STUDY DESIGN: Pilot, prospective study. METHODS: Adult participants with a
      clinical diagnosis of LPR collected whole saliva samples on regular intervals for
      a day, and upon experiencing symptoms attributed to LPR. Patients were selected
      on the basis of presence of severe symptoms and laryngoscopic findings of
      laryngopharyngeal reflux and symptoms of gastroesopharyngeal reflux. They
      reported voice disorders, dysphagia, throat clearing, excessive secretions,
      breathing difficulties, cough, globus sensation and throat pain. Control
      participants reported the absence of pharyngeal and laryngeal symptoms and of
      symptoms of gastroesophageal reflux. Saliva samples were assayed with fibrinogen
      on an agarose gel plate. The detection of pepsin was based on the presence of
      peptic activity which was qualitatively evaluated. RESULTS: The control
      participants had negative assays. No saliva samples from the LPR patients,
      collected at regular sampling, tested positive for pepsin. All the samples
      collected at the presence of symptoms and following regurgitation episodes tested
      negative for pepsin. Saliva samples pH ranged from 7 to 8. CONCLUSIONS: Pepsin
      was not detected, with an activity assay, in the saliva of patients with a
      clinical diagnosis of LPR. A concentration method might be more sensitive
      although saliva and swallowing physiology renders the detection of pepsin in the
      saliva difficult.

PMID- 19582212
TI  - Ulnar sesamoid's fracture of the thumb: an unusual injury and review of the
      literature.
AB  - BACKGROUND: It concerns an unusual injury which is the result of a violent
      hyperextension or abduction of the pollex and even less frequently by direct
      injury. AIM: To increase our sensitivity and observation regarding thumb's
      injuries, because it is possible a fracture of the sesamoid not to be diagnosed.
      MATERIAL AND METHOD: We present a case of an adult man, 35 years old, who
      suffered a violent hyperextension of the right pollex. The contribution of
      digital X-ray examination, which demonstrated a fracture of the ulnar sesamoid of
      the pollex was very important. The fracture was treated with fixation with
      elastic bandages for two weeks. RESULTS: Follow up of the patient six weeks and
      six months after the injury, demonstrated a total recovery of the function of the
      pollex and callousness of the fracture, respectively. CONCLUSION: Fracture of
      sesamoid bones of the thumb is a rare injury, not usually diagnosed, but it has
      good prognosis when treated properly.

PMID- 19582214
TI  - Voltage-dependent anion channel 2 of Arabidopsis thaliana (AtVDAC2) is involved
      in ABA-mediated early seedling development.
AB  - The voltage-dependent anion channel (VDAC) is the major transport protein in the
      outer membrane of mitochondria and plays crucial roles in energy metabolism,
      apoptosis, and metabolites transport. In plants, the expression of VDACs can be
      affected by different stresses, including drought, salinity and pathogen defense.
      In this study, we investigated the expression pattern of AtVDAC2 in A. thaliana
      and found ABA suppressed the accumulation of AtVDAC2 transcripts. Further,
      phenotype analysis of this VDAC deregulated-expression transgenic Arabidopsis
      plants indicated that AtVDAC2 anti-sense line showed an ABA-insensitivity
      phenotype during the early seedling development under ABA treatment. The results
      suggested that AtVDAC2 might be involved in ABA signaling in A. thaliana.

PMID- 19582215
TI  - Association study between BDNF gene polymorphisms and autism by three-dimensional
      gel-based microarray.
AB  - Single nucleotide polymorphisms (SNPs) are important markers which can be used in
      association studies searching for susceptible genes of complex diseases. High
      throughput methods are needed for SNP genotyping in a large number of samples. In
      this study, we applied polyacrylamide gel-based microarray combined with dual
      color hybridization for association study of four BDNF polymorphisms with autism.
      All the SNPs in both patients and controls could be analyzed quickly and
      correctly. Among four SNPs, only C270T polymorphism showed significant
      differences in the frequency of the allele (chi(2) = 7.809, p = 0.005) and
      genotype (chi(2) = 7.800, p = 0.020). In the haplotype association analysis,
      there was significant difference in global haplotype distribution between the
      groups (chi(2) = 28.19, p = 3.44e-005). We suggest that BDNF has a possible role
      in the pathogenesis of autism. The study also show that the polyacrylamide gel
      based microarray combined with dual-color hybridization is a rapid, simple and
      high-throughput method for SNPs genotyping, and can be used for association study
      of susceptible gene with disorders in large samples.

PMID- 19582216
TI  - Purification, crystallization and preliminary x-ray crystallographic studies of
      RAIDD Death-Domain (DD).
AB  - Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress
      induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and
      Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase
      Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions
      with Caspase-2 and PIDD through CARD and DD respectively and formation of
      PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into
      pET26b vector was expressed in E. coli cells and purified by nickel affinity
      chromatography and gel filtration. Although it has been known that the most DDs
      are not soluble in physiological condition, RAIDD DD was soluble and interacts
      tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has
      been crystallized. Crystals are trigonal and belong to space group P3(1)21 (or
      its enantiomorph P3(2)21) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9
      A and gamma = 120 degrees . The crystals were obtained at room temperature and
      diffracted to 2.0 A resolution.

PMID- 19582213
TI  - An updated review of tyrosinase inhibitors.
AB  - Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase,
      which catalyzes the first two steps in mammalian melanogenesis and is responsible
      for enzymatic browning reactions in damaged fruits during post-harvest handling
      and processing. Neither hyperpigmentation in human skin nor enzymatic browning in
      fruits are desirable. These phenomena have encouraged researchers to seek new
      potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys
      tyrosinase inhibitors newly discovered from natural and synthetic sources. The
      inhibitory strength is compared with that of a standard inhibitor, kojic acid,
      and their inhibitory mechanisms are discussed.

PMID- 19582219
TI  - Tryptophanase-catalyzed L-tryptophan synthesis from D-serine in the presence of
      diammonium hydrogen phosphate.
AB  - Tryptophanase, an enzyme with extreme absolute stereospecificity for optically
      active stereoisomers, catalyzes the synthesis of l-tryptophan from l-serine and
      indole through a beta-substitution mechanism of the ping-pong type, and has no
      activity on d-serine. We previously reported that tryptophanase changed its
      stereospecificity to degrade d-tryptophan in highly concentrated diammonium
      hydrogen phosphate, (NH(4))(2)HPO(4) solution. The present study provided the
      same stereospecific change seen in the d-tryptophan degradation reaction also
      occurs in tryptophan synthesis from d-serine. Tryptophanase became active to d
      serine to synthesize l-tryptophan in the presence of diammonium hydrogen
      phosphate. This reaction has never been reported before. d-serine seems to
      undergo beta-replacement via an enzyme-bonded alpha-aminoacylate intermediate to
      yield l-tryptophan.

PMID- 19582218
TI  - QSPR studies on aqueous solubilities of drug-like compounds.
AB  - A rapidly growing area of modern pharmaceutical research is the prediction of
      aqueous solubility of drug-sized compounds from their molecular structures. There
      exist many different reasons for considering this physico-chemical property as a
      key parameter: the design of novel entities with adequate aqueous solubility
      brings many advantages to preclinical and clinical research and development,
      allowing improvement of the Absorption, Distribution, Metabolization, and
      Elimination/Toxicity profile and "screenability" of drug candidates in High
      Throughput Screening techniques. This work compiles recent QSPR linear models
      established by our research group devoted to the quantification of aqueous
      solubilities and their comparison to previous research on the topic.

PMID- 19582220
TI  - Application of ionic liquids in high performance reversed-phase chromatography.
AB  - Ionic liquids, considered "green" chemicals, are widely used in many areas of
      analytical chemistry due to their unique properties. Recently, ionic liquids have
      been used as a kind of novel additive in separation and combined with silica to
      synthesize new stationary phase as separation media. This review will focus on
      the properties and mechanisms of ionic liquids and their potential applications
      as mobile phase modifier and surface-bonded stationary phase in reversed-phase
      high performance liquid chromatography (RP-HPLC). Ionic liquids demonstrate
      advantages and potential in chromatographic field.

PMID- 19582221
TI  - The eukaryotic cell originated in the integration and redistribution of
      hyperstructures from communities of prokaryotic cells based on molecular
      complementarity.
AB  - In the "ecosystems-first" approach to the origins of life, networks of non
      covalent assemblies of molecules (composomes), rather than individual protocells,
      evolved under the constraints of molecular complementarity. Composomes evolved
      into the hyperstructures of modern bacteria. We extend the ecosystems-first
      approach to explain the origin of eukaryotic cells through the integration of
      mixed populations of bacteria. We suggest that mutualism and symbiosis resulted
      in cellular mergers entailing the loss of redundant hyperstructures, the
      uncoupling of transcription and translation, and the emergence of introns and
      multiple chromosomes. Molecular complementarity also facilitated integration of
      bacterial hyperstructures to perform cytoskeletal and movement functions.

PMID- 19582217
TI  - Trends in the molecular pathogenesis and clinical therapeutics of common
      neurodegenerative disorders.
AB  - The term neurodegenerative disorders, encompasses a variety of underlying
      conditions, sporadic and/or familial and are characterized by the persistent loss
      of neuronal subtypes. These disorders can disrupt molecular pathways, synapses,
      neuronal subpopulations and local circuits in specific brain regions, as well as
      higher-order neural networks. Abnormal network activities may result in a vicious
      cycle, further impairing the integrity and functions of neurons and synapses, for
      example, through aberrant excitation or inhibition. The most common
      neurodegenerative disorders are Alzheimer's disease, Parkinson's disease,
      Amyotrophic Lateral Sclerosis and Huntington's disease. The molecular features of
      these disorders have been extensively researched and various unique
      neurotherapeutic interventions have been developed. However, there is an enormous
      coercion to integrate the existing knowledge in order to intensify the
      reliability with which neurodegenerative disorders can be diagnosed and treated.
      The objective of this review article is therefore to assimilate these disorders'
      in terms of their neuropathology, neurogenetics, etiology, trends in
      pharmacological treatment, clinical management, and the use of innovative
      neurotherapeutic interventions.

PMID- 19582222
TI  - Periodic density functional theory investigation of the uranyl ion sorption on
      three mineral surfaces: a comparative study.
AB  - Canister integrity and radionuclides retention is of prime importance for
      assessing the long term safety of nuclear waste stored in engineered geologic
      depositories. A comparative investigation of the interaction of uranyl ion with
      three different mineral surfaces has thus been undertaken in order to point out
      the influence of surface composition on the adsorption mechanism(s). Periodic DFT
      calculations using plane waves basis sets with the GGA formalism were performed
      on the TiO(2)(110), Al(OH)(3)(001) and Ni(111) surfaces. This study has clearly
      shown that three parameters play an important role in the uranyl adsorption
      mechanism: the solvent (H(2)O) distribution at the interface, the nature of the
      adsorption site and finally, the surface atoms' protonation state.

PMID- 19582223
TI  - Measurement of nanomolar dissociation constants by titration calorimetry and
      thermal shift assay - radicicol binding to Hsp90 and ethoxzolamide binding to
      CAII.
AB  - The analysis of tight protein-ligand binding reactions by isothermal titration
      calorimetry (ITC) and thermal shift assay (TSA) is presented. The binding of
      radicicol to the N-terminal domain of human heat shock protein 90 (Hsp90alphaN)
      and the binding of ethoxzolamide to human carbonic anhydrase (hCAII) were too
      strong to be measured accurately by direct ITC titration and therefore were
      measured by displacement ITC and by observing the temperature-denaturation
      transitions of ligand-free and ligand-bound protein. Stabilization of both
      proteins by their ligands was profound, increasing the melting temperature by
      more than 10 masculineC, depending on ligand concentration. Analysis of the
      melting temperature dependence on the protein and ligand concentrations yielded
      dissociation constants equal to 1 nM and 2 nM for Hsp90alphaN-radicicol and hCAII
      ethoxzolamide, respectively. The ligand-free and ligand-bound protein fractions
      melt separately, and two melting transitions are observed. This phenomenon is
      especially pronounced when the ligand concentration is equal to about half the
      protein concentration. The analysis compares ITC and TSA data, accounts for two
      transitions and yields the ligand binding constant and the parameters of protein
      stability, including the Gibbs free energy and the enthalpy of unfolding.

PMID- 19582224
TI  - Precambrian lunar volcanic protolife.
AB  - Five representative terrestrial analogs of lunar craters are detailed relevant to
      Precambrian fumarolic activity. Fumarolic fluids contain the ingredients for
      protolife. Energy sources to derive formaldehyde, amino acids and related
      compounds could be by flow charging, charge separation and volcanic shock. With
      no photodecomposition in shadow, most fumarolic fluids at 40 K would persist over
      geologically long time periods. Relatively abundant tungsten would permit
      creation of critical enzymes, Fischer-Tropsch reactions could form polycyclic
      aromatic hydrocarbons and soluble volcanic polyphosphates would enable assembly
      of nucleic acids. Fumarolic stimuli factors are described. Orbital and lander
      sensors specific to protolife exploration including combined Raman/laser-induced
      breakdown spectrocsopy are evaluated.

PMID- 19582225
TI  - Amino acid synthesis in a supercritical carbon dioxide - water system.
AB  - Mars is a CO(2)-abundant planet, whereas early Earth is thought to be also CO(2)
      abundant. In addition, water was also discovered on Mars in 2008. From the facts
      and theory, we assumed that soda fountains were present on both planets, and this
      affected amino acid synthesis. Here, using a supercritical CO(2)/liquid H(2)O
      (10:1) system which mimicked crust soda fountains, we demonstrate production of
      amino acids from hydroxylamine (nitrogen source) and keto acids (oxylic acid
      sources). In this research, several amino acids were detected with an amino acid
      analyzer. Moreover, alanine polymers were detected with LC-MS. Our research
      lights up a new pathway in the study of life's origin.

PMID- 19582226
TI  - Variation in dehydration tolerance, ABA sensitivity and related gene expression
      patterns in D-genome progenitor and synthetic hexaploid wheat lines.
AB  - The wild wheat Aegilops tauschii Coss. has extensive natural variation available
      for breeding of common wheat. Drought stress tolerance is closely related to
      abscisic acid (ABA) sensitivity. In this study, 17 synthetic hexaploid wheat
      lines, produced by crossing the tetraploid wheat cultivar Langdon with 17
      accessions of Ae. tauschii, were used for comparative analysis of natural
      variation in drought tolerance and ABA sensitivity. Ae. tauschii showed wide
      natural variation, with weak association between the traits. Drought-sensitive
      accessions of Ae. tauschii exhibited significantly less ABA sensitivity. D-genome
      variations observed at the diploid genome level were not necessarily reflected in
      synthetic wheats. However, synthetic wheats derived from the parental Ae.
      tauschii accessions with high drought tolerance were significantly more tolerant
      to drought stress than those from drought-sensitive accessions. Moreover,
      synthetic wheats with high drought tolerance showed significantly higher ABA
      sensitivity than drought-sensitive synthetic lines. In the hexaploid genetic
      background, therefore, weak association of ABA sensitivity with drought tolerance
      was observed. To study differences in gene expression patterns between stress
      tolerant and -sensitive lines, levels of two Cor/Lea and three transcription
      factor gene transcripts were compared. The more tolerant accession of Ae.
      tauschii tended to accumulate more abundant transcripts of the examined genes
      than the sensitive accession under stress conditions. The expression patterns in
      the synthetic wheats seemed to be additive for parental lines exposed to drought
      and ABA treatments. However, the transcript levels of transcription factor genes
      in the synthetic wheats did not necessarily correspond to the postulated levels
      based on expression in parental lines. Allopolyploidization altered the
      expression levels of the stress-responsive genes in synthetic wheats.

PMID- 19582227
TI  - Titration calorimetry standards and the precision of isothermal titration
      calorimetry data.
AB  - Current Isothermal Titration Calorimetry (ITC) data in the literature have
      relatively high errors in the measured enthalpies of protein-ligand binding
      reactions. There is a need for universal validation standards for titration
      calorimeters. Several inorganic salt co-precipitation and buffer protonation
      reactions have been suggested as possible enthalpy standards. The performances of
      several commercial calorimeters, including the VP-ITC, ITC200, and Nano ITC-III,
      were validated using these suggested standard reactions.

PMID- 19582230
TI  - Lattice strain due to an atomic vacancy.
AB  - Volumetric strain can be divided into two parts: strain due to bond distance
      change and strain due to vacancy sources and sinks. In this paper, efforts are
      focused on studying the atomic lattice strain due to a vacancy in an FCC metal
      lattice with molecular dynamics simulation (MDS). The result has been compared
      with that from a continuum mechanics method. It is shown that using a continuum
      mechanics approach yields constitutive results similar to the ones obtained based
      purely on molecular dynamics considerations.

PMID- 19582229
TI  - Termite resistance of MDF panels treated with various boron compounds.
AB  - In this study, the effects of various boron compounds on the termite resistance
      of MDF panels were evaluated. Either borax (BX), boric acid (BA), zinc borate
      (ZB), or sodium perborate tetrahydrate (SPT) were added to urea-formaldehyde (UF)
      resin at target contents of 1%, 1.5%, 2% and 2.5% based on dry fiber weight. The
      panels were then manufactured using 12% urea-formaldehyde resin and 1% NH(4)Cl.
      MDF samples from the panels were tested against the subterranean termites,
      Coptotermes formosanus Shiraki. Laboratory termite resistance tests showed that
      all samples containing boron compounds had greater resistance against termite
      attack compared to untreated MDF samples. At the second and third weeks of
      exposure, nearly 100% termite mortalities were recorded in all boron compound
      treated samples. The highest termite mortalities were determined in the samples
      with either BA or BX. Also, it was found that SPT showed notable performance on
      the termite mortality. As chemical loadings increased, termite mortalities
      increased, and at the same time the weight losses of the samples decreased.

PMID- 19582228
TI  - Yeast two-hybrid, a powerful tool for systems biology.
AB  - A key property of complex biological systems is the presence of interaction
      networks formed by its different components, primarily proteins. These are
      crucial for all levels of cellular function, including architecture, metabolism
      and signalling, as well as the availability of cellular energy. Very stable, but
      also rather transient and dynamic protein-protein interactions generate new
      system properties at the level of multiprotein complexes, cellular compartments
      or the entire cell. Thus, interactomics is expected to largely contribute to
      emerging fields like systems biology or systems bioenergetics. The more recent
      technological development of high-throughput methods for interactomics research
      will dramatically increase our knowledge of protein interaction networks. The two
      most frequently used methods are yeast two-hybrid (Y2H) screening, a well
      established genetic in vivo approach, and affinity purification of complexes
      followed by mass spectrometry analysis, an emerging biochemical in vitro
      technique. So far, a majority of published interactions have been detected using
      an Y2H screen. However, with the massive application of this method, also some
      limitations have become apparent. This review provides an overview on available
      yeast two-hybrid methods, in particular focusing on more recent approaches. These
      allow detection of protein interactions in their native environment, as e.g. in
      the cytosol or bound to a membrane, by using cytosolic signalling cascades or
      split protein constructs. Strengths and weaknesses of these genetic methods are
      discussed and some guidelines for verification of detected protein-protein
      interactions are provided.

PMID- 19582231
TI  - Calculation of the aqueous thermodynamic properties of citric acid cycle
      intermediates and precursors and the estimation of high temperature and pressure
      equation of state parameters.
AB  - The citric acid cycle (CAC) is the central pathway of energy transfer for many
      organisms, and understanding the origin of this pathway may provide insight into
      the origins of metabolism. In order to assess the thermodynamics of this key
      pathway for microorganisms that inhabit a wide variety of environments,
      especially those found in high temperature environments, we have calculated the
      properties and parameters for the revised Helgeson-Kirkham-Flowers equation of
      state for the major components of the CAC. While a significant amount of data is
      not available for many of the constituents of this fundamental pathway, methods
      exist that allow estimation of these missing data.

PMID- 19582232
TI  - Folding mechanism of beta-hairpin trpzip2: heterogeneity, transition state and
      folding pathways.
AB  - We review the studies on the folding mechanism of the beta-hairpin tryptophan
      zipper 2 (trpzip2) and present some additional computational results to refine
      the picture of folding heterogeneity and pathways. We show that trpzip2 can have
      a two-state or a multi-state folding pattern, depending on whether it folds
      within the native basin or through local state basins on the high-dimensional
      free energy surface; Trpzip2 can fold along different pathways according to the
      packing order of tryptophan pairs. We also point out some important problems
      related to the folding mechanism of trpzip2 that still need clarification, e.g.,
      a wide distribution of the computed conformations for the transition state
      ensemble.

PMID- 19582233
TI  - Inactivation and unfolding of the hyperthermophilic inorganic pyrophosphatase
      from Thermus thermophilus by sodium dodecyl sulfate.
AB  - Inorganic pyrophosphatase (PPase, EC 3.6.1.1) is an essential constitutive enzyme
      for energy metabolism and clearance of excess pyrophosphate. In this research, we
      investigated the sodium dodecyl sulfate (SDS)-induced inactivation and unfolding
      of PPase from Thermus thermophilus (T-PPase), a hyperthermophilic enzyme. The
      results indicated that like many other mesophilic enzymes, T-PPase could be fully
      inactivated at a low SDS concentration of 2 mM. Using an enzyme activity assay,
      SDS was shown to act as a mixed type reversible inhibitor, suggesting T-PPase
      contained specific SDS binding sites. At high SDS concentrations, T-PPase was
      denatured via a two-state process without the accumulation of any intermediate,
      as revealed by far-UV CD and intrinsic fluorescence. A comparison of the
      inactivation and unfolding data suggested that the inhibition might be caused by
      the specific binding of the SDS molecules to the enzyme, while the unfolding
      might be caused by the cooperative non-specific binding of SDS to T-PPase. The
      possible molecular mechanisms underlying the mixed type inhibition by SDS was
      proposed to be caused by the local conformational changes or altered charge
      distributions.

PMID- 19582235
TI  - Mouthguard retention: is design or accuracy of fit more critical?
AB  - AIM: To examine the influence of the accuracy of fit on mouthguard retention in
      relation to mouthguard outline location. MATERIALS AND METHODS: Mouthguards were
      fabricated on a fully dentate maxillary cast with 4-mm thick ethylene vinyl
      acetate sheets using a well-dried cast (VD) and on a wet cast (VW) with a vacuum
      forming machine. Mouthguards were also made with a pressure-forming machine (P).
      The mouthguard outline was set at 4 mm from the cervical margin (control, C), the
      palatal outline was set at the cervical margin (Pa), and the buccal outline was
      extended to the buccal fold (Bu). A dislodging force perpendicular to the
      occlusal plane was applied at the first molar on the universal testing machine.
      Results were analyzed using ANOVA with Scheffe's test (P < .05). RESULTS: Using
      the VW, the retentive forces were statistically smaller at Pa compared to Ca or
      Bu (C: 58 +/- 17 gf, Pa: 36 +/- 7 gf , Bu: 50+/-8 gf) (P < .05). There were no
      statistical differences between VD (C: 116+/-27 gf, Pa: 86+/-15 gf, Bu: 92+/-7
      gf) and group P (C: 133+/-31 gf, Pa: 139+/-24 gf, Bu: 136+/-17 gf). CONCLUSIONS:
      The results indicate that mouthguard retention is closely related to the accuracy
      of fit at the cervical undercut area rather than the outline location.

PMID- 19582237
TI  - Osteomyelitis of the mandible following third molar surgery: a regrettable
      consequence in a healthy patient.
AB  - This clinical case describes mandibular osteomyelitis in a healthy 31-year-old
      man as a severe complication following third molar removal. Recurrent abscess
      formations were treated with intensive therapy involving antibiotics, surgical
      debridement of the affected region, and hyperbaric oxygen. In the follow-up,
      despite microbiologic study to determine the indicated treatment approach, a
      severe osteomyelitis was present, clinically and radiographically. Finally, a
      partial resection of the mandible, including exarticulation, was indicated to
      manage this severe complication.

PMID- 19582238
TI  - Reactive repositioning of pathologically migrated teeth following periodontal
      therapy.
AB  - Pathologically migrated teeth generally require orthodontic correction, as well
      as restorative options, as treatment. The term reactive positioning has been used
      to describe tooth movement that occurs without the use of appliances after
      periodontal treatment. This article describes the case of a young woman with
      periodontal attachment loss and distolabial pathologic migration of the maxillary
      central incisors, with midline diastema formation. Papilla preservation flap
      surgery was performed on the maxillary anterior segment, which spontaneously
      resolved the midline diastema without orthodontic treatment. This article also
      explores the possible mechanisms (hypotheses) for such an outcome of a simple
      periodontal surgery.

PMID- 19582234
TI  - Protease inhibitors from plants with antimicrobial activity.
AB  - Antimicrobial proteins (peptides) are known to play important roles in the innate
      host defense mechanisms of most living organisms, including plants, insects,
      amphibians and mammals. They are also known to possess potent antibiotic activity
      against bacteria, fungi, and even certain viruses. Recently, the rapid emergence
      of microbial pathogens that are resistant to currently available antibiotics has
      triggered considerable interest in the isolation and investigation of the mode of
      action of antimicrobial proteins (peptides). Plants produce a variety of proteins
      (peptides) that are involved in the defense against pathogens and invading
      organisms, including ribosome-inactivating proteins, lectins, protease inhibitors
      and antifungal peptides (proteins). Specially, the protease inhibitors can
      inhibit aspartic, serine and cysteine proteinases. Increased levels of trypsin
      and chymotrypsin inhibitors correlated with the plants resistance to the
      pathogen. Usually, the purification of antimicrobial proteins (peptides) with
      protease inhibitor activity was accomplished by salt-extraction, ultrafiltration
      and C(18) reverse phase chromatography, successfully. We discuss the relation
      between antimicrobial and anti-protease activity in this review. Protease
      inhibitors from plants potently inhibited the growth of a variety of pathogenic
      bacterial and fungal strains and are therefore excellent candidates for use as
      the lead compounds for the development of novel antimicrobial agents.

PMID- 19582239
TI  - Uprighting impacted mandibular second molars with orthodontic elastic separating
      rings.
AB  - A 16-year-old girl presented with complaints of recurrent spontaneous pain in the
      mandibular second molar region. Treatment favored use of a simple uprighting
      technique involving orthodontic elastic separating rings.

PMID- 19582240
TI  - Premolar cuspal flexure as a function of restorative material and occlusal
      contact location.
AB  - OBJECTIVE: To measure cuspal flexure of intact and restored maxillary premolars
      with different restorative materials and occlusal contacts. METHOD AND MATERIALS:
      Micro?computed tomography data were used to generate finite-element models with a
      mesio-occlusaldistal (MOD) cavity preparation and the corresponding restoration.
      The tooth parts were imported in finite-element software to create 3D volumetric
      models. Occlusal loading either in enamel, at restoration margin, or in
      restorative material was simulated by linear contact analysis. Cuspal widening
      was measured for the different contact locations and restorative conditions
      (unaltered tooth, MOD porcelain, and composite-inlay restorations). RESULTS: For
      a given material property, contacts in restoration generated the least amount of
      cuspal deformation, followed by the enamel contacts and contacts at restoration
      margin. Models of the intact tooth and ceramic inlay behaved similarly (cuspal
      widening at 100 N ranging from 1.8 to 3.0 microm and 1.6 to 2.6 microm,
      respectively). Cuspal flexure was increased in the MOD composite resin
      restorations (3.4 to 5.7 microm at 100 N of axial force). The least amount of
      deformation was generated in the ceramic inlay with contacts in only restoration
      (1.6 microm at 100 N) and the largest in the composite inlay with contacts at
      restoration margins (5.7 microm at 100 N). For the composite restoration,
      antagonist contacts at restoration margins were less favorable compared to
      located on either enamel or the restoration itself. CONCLUSION: A relatively
      small cuspal deformation was observed in all models. There is an increased cusp
      stabilizing effect of ceramic inlays compared to composite ones.

PMID- 19582241
TI  - Root coverage with 2 connective tissue grafts obtained from the same location
      using a single-incision technique.
AB  - A single-incision technique was introduced to minimize the size of the palatal
      wound and allow for primary closure of the donor site, which may result in
      reduced postoperative pain. It is sometimes necessary to repeatedly use the same
      area of a patient's palate for consecutive connective tissue grafts because of
      limitations caused by inadequate tissue or vascular anatomy. This case
      presentation describes the clinical results of 2 subepithelial grafts for root
      coverage from the same donor area at different times using the single-incision
      technique. The root coverage obtained with both the first and second connective
      tissue grafts from the same donor area using the single-incision technique at a 6
      week interval showed predictable results, with reduction of dentin
      hypersensitivity without probing defect or significant complication. This
      approach may be an option when multiple connective tissue grafts are needed. The
      presented results need to be validated in further large case series or case
      controlled studies.

PMID- 19582242
TI  - Classification and prognosis evaluation of individual teeth--a comprehensive
      approach.
AB  - Following a complete evaluation of the patient, treatment planning requires the
      analysis of individual teeth, accurate diagnosis, and prognosis evaluation.
      Currently, there is no accepted comprehensive, standardized, and meaningful
      classification system for the evaluation of individual teeth that offers a common
      language for dental professionals. A search was conducted reviewing existing
      literature relating to classification and prognostication of individual teeth.
      The dimensions determined to be of importance to gain an overall perspective of
      the individual relative tooth prognosis were the periodontal, restorative,
      endodontic, and occlusal plane perspectives. The authors present a comprehensive
      classification system by conjugating the literature and currently accepted
      concepts in dentistry. This easy-to-use system assesses the condition of
      individual teeth and enables a relative prognostic value to be attached to those
      teeth based on tooth condition and patient-level factors.

PMID- 19582243
TI  - Dental radiographic guidelines: a review.
AB  - The 2004 American Dental Association (ADA)/US Food and Drug Administration (FDA)
      radiographic selection criteria and guidelines were reviewed and compared with
      the prior radiographic selection criteria and guidelines. The authors reviewed
      the publications from the US FDA, US Department of Health and Human Services, and
      National Council on Radiation Protection and Measurements. The positions outlined
      by the Canadian Dental Association and the European Commission were also reviewed
      and compared to US guidelines. The FDA guidelines were first published in 1987,
      and several changes have been made to them over the years. Recent literature
      reveals that the general compliance of these guidelines is very low, especially
      within dental schools in the United States and Canada. Little is known about the
      compliance outside of the dental school environment; however, it is expected to
      be low for various reasons. In 2007, the International Commission on Radiological
      Protection (ICRP) revised its estimates of tissue radiosensitivity, which
      resulted in effective doses of dental radiographs 32% to 422% higher than the
      1990 ICRP guidelines. Flow charts summarizing the latest guidelines were
      developed to facilitate general compliance among practitioners. Based on the
      literature reviewed and the recent ICRP findings, it would be prudent for dental
      health care professionals to follow dental radiographic guidelines.

PMID- 19582244
TI  - Dexamucobase: a novel treatment for oral aphthous ulceration.
AB  - OBJECTIVES: Recurrent oral aphthous ulceration is a common condition treated with
      topical anti-inflammatory drugs, such as triamcinolone acetonide in Orabase
      (Kenalog in Orabase, Bristol-Myers Squibb). The aim of the study was to
      synthesize a novel dental paste containing dexamethasone and assess the
      therapeutic effect of this paste in comparison with a commonly used treatment,
      triamcinolone acetonide in Orabase, in oral aphthous ulceration. METHOD AND
      MATERIALS: The design was a case-control study. The setting was the laboratory of
      postgraduate students in the College of Pharmacy, University of Mosul, Iraq.
      Clinical evaluation of the paste was conducted in the outpatient clinic of the
      Oral Medicine Department, College of Dentistry, University of Baghdad, Iraq. The
      novel paste (named dexamucobase) was prepared under aseptic conditions and
      evaluated for its therapeutic effect in 53 patients with recurrent aphthous
      stomatitis, in comparison with 37 patients treated with triamcinolone acetonide
      in Orabase. RESULTS: Healing of the ulcer was significantly faster (P < .001),
      and adverse effects were significantly reduced (P < .01) for the dexamucobase
      treatment compared to Kenalog in Orabase. There was no significant difference in
      the speed of pain reduction between the dexamucobase treatment compared to
      Kenalog in Orabase. CONCLUSIONS: The novel dexamucobase was found to be equally
      effective in treating oral aphthous ulceration, with some advantages, as the
      widely used preparation Kenalog in Orabase.

PMID- 19582245
TI  - Analysis of retention and wear of ball attachments.
AB  - OBJECTIVE: To evaluate the retention and the wear of different prefabricated
      precision ball attachments consecutively during long-term use. METHOD AND
      MATERIALS: Six commercially available ball attachment systems were selected. The
      balls were attached to stylized implants fixed in metal casts. The matrices were
      fixed in a stylized unilaterally removable partial denture (RPD). Using a chewing
      simulator with 8 units, 50,000 joining and separating cycles of the matrices were
      performed. After each joining movement, an eccentric load of 100 N was applied to
      the RPD at a distance of 12 mm from the ball attachment. The retention forces
      were measured at intervals. RESULTS: Initially, median retentive forces varied
      between 8.2 N and 14.0 N. During the test, patterns in retention changes were
      identified. At the end of the test, one group with a matrix using precious alloy
      lamellae and a titanium ball showed significantly higher median retention forces
      (10.4 N) than the other ball attachments (1.0 N to 3.7 N). Also, the wear of the
      ball attachments varied considerably. CONCLUSION: Within the limitations of this
      study, the material combination of a precious gold alloy matrix and a titanium
      ball seems to be favorable for long-term retention.

PMID- 19582246
TI  - Implants inserted in fresh-frozen bone: a retrospective analysis of 88 implants
      loaded 4 months after insertion.
AB  - OBJECTIVE: In the previous decade, several reports have been published regarding
      implants inserted in autografts, but none have analyzed implants inserted in
      fresh-frozen bone allografts. Thus, a retrospective study was planned to verify
      if 4-months' delay from grafting to implant insertion is a safe period before
      prosthetic rehabilitation of implants placed in fresh-frozen bone allografts.
      METHOD AND MATERIALS: Between December 2003 and December 2006, 22 patients (10
      women and 12 men with a median age of 51 years) underwent grafting with
      horizontal augmentation without membrane and 88 implants inserted thereafter. The
      mean implant follow-up was 27 months. Implants used were 30 double etched (3i,
      Osseotite, Biomet), 10 SLA1 (Astratech), 26 anodic oxidized (Nobel Biocare), 12
      CaPO4 ceramic-blasted (Lifecore Biomedical), 7 SLA2 (Sweden and Martina Spa), 2
      ITI (Straumann), and 1 Biotec (Povolaro di Dueville). Implant diameter and length
      ranged from 3.25 to 5.0 mm and from 8.0 to 15.0 mm, respectively. Implants were
      inserted to replace 10 incisors, 7 canines, 36 premolars, and 35 molars. RESULTS:
      No implants were lost (ie, survival rate = 100%). No difference was detected when
      comparing implants loaded after 4 months versus those loaded after 6 or more
      months (209 implants). CONCLUSION: Four-months' delay from grafting to implant
      insertion is a safe period to obtain a high survival rate and success rate for
      implants inserted in fresh-frozen bone.

PMID- 19582247
TI  - Intraexaminer reliability of measurement of tooth color by spectrophotometry.
AB  - OBJECTIVE: To evaluate intraexaminer reliability in measurement of basic tooth
      color by use of a clinically applicable spectrophotometer. METHOD AND MATERIALS:
      Three examiners determined the L* (lightness), C* (chroma), and h* (hue) values
      and tooth color according to the Vita 3D-Master shade guide system (Vident),
      twice for 161 anterior teeth of 19 subjects by use of a spectrophotometer (Vita
      Easyshade 1, Vita Zahnfabrik). Between the 2 measurements on each tooth, the
      investigators had to completely remove the probe tip from the mouth. The
      reliability of the measurements was observed, and deviations between the 2 L*C*h*
      measurements, as well as DeltaEab for the measurements, were calculated. RESULTS:
      Exact agreement of chosen shade tab according to the 3D-Master shade guide was
      achieved in 48% of cases. Mean DeltaL*, DeltaC*, and Deltah* for all examiners
      were 1.9 (SD 1.7), 1.3 (SD 1.3), and 0.5 degrees (SD 0.7 degrees), respectively.
      The maximum deviation was 9 for DeltaL*, 7 for DeltaC*, and 3 degrees for
      Deltah*. Mean DeltaEab for the measurements was 2.7 (SD 1.8, range 0 to 9.5).
      CONCLUSION: Intraexaminer reliability was usually acceptable, although a
      clinically relevant difference between the 2 measurements of an examiner was
      occasionally observed. This uncertainty should be borne in mind in clinical
      routine and in studies reporting changes in color, eg, studies of tooth
      bleaching.

PMID- 19582248
TI  - The incidence of maxillary sinus retention cysts in orthodontic patients.
AB  - Maxillary sinus retention cysts are occasionally found on dental radiographs. The
      objective of this study was to verify the frequency of maxillary sinus retention
      cysts in consecutive panoramic radiographs from 173 patients (77 males, 96
      females) in an orthodontic office. The chi-square test was used for statistical
      analysis. Ten patients (5.8%) of the total sample presented a maxillary sinus
      retention cyst. Males had a higher frequency (9.1%) than females (3.1%), but this
      difference was not significant (P>.05). Overall, the frequency of maxillary sinus
      retention cysts in orthodontic patients is rather low and does not differ from
      the general population.

PMID- 19582249
TI  - Time and space are most valuable.

PMID- 19582250
TI  - Incidence of bridging and dimensions of sella turcica in Class I and III Turkish
      adult female patients.
AB  - Mineralization of the interclinoid ligament of the sella turcica, or sella
      turcica bridging, has been associated with severe craniofacial deviations. The
      aim of this study was to evaluate the incidence of sella turcica bridging, sella
      turcica dimensions, and skeletal variables in 57 Class I (mean age, 27.2 +/- 5.3
      years) and 61 Class III (mean age, 25.8 +/- 4.6 years) Turkish adult females.
      Sella bridging was found in three (5%) of the Class I and 11 (18%) of the Class
      III individuals (P<.010). The association between sella turcica bridging and
      manifest skeletal Class III malocclusions was statistically significant according
      to the chi-square test (P<.050). No significant differences in sella turcica
      dimensions were found between the Class I and Class III patients. Skeletal
      variables that differed significantly were SNB (P=.004), ANB (P=.002), and NAPg
      (P=.000) angles and N-B (P=.030), N-Pg (P=.003), Go-Pg (P=.007), and TM-Pg
      (P=.002) dimensions.

PMID- 19582251
TI  - Treatment of an anterior open bite with the multiloop archwire technique.
AB  - This is a treatment report of a patient with an anterior open bite and
      predominance of vertical growth. Multiloop edgewise archwire (MEAW) mechanics
      were used and resulted in an efficient bite closure and good occlusion. For
      retention, a bonded 3-3 retainer was used in the mandible whereas a wraparound
      retainer was employed in the maxilla.

PMID- 19582252
TI  - Comparison of the frontal esthetic preferences in the lower facial portion of
      Koreans and Caucasians.
AB  - AIM: To compare the differences in frontal esthetics in the lower face among
      Caucasian models, Korean models, and Korean nonmodels. METHODS: The sample
      consisted of three groups comprising 36 Caucasian models, 30 Korean models, and
      26 Korean nonmodels. Their frontal photos were scanned, and 12 distances, five
      angles, lip perimeter, and lip area were measured. Differences among groups were
      compared using one-way analysis of variance (ANOVA) and Tukey's test. RESULTS:
      There was no significant difference in the upper lip height among the three
      groups. The Korean models had shorter lower lip to chin height than the two other
      groups. Full lip width was wider in the Korean and Caucasian models than in the
      Korean nonmodels. The Caucasian models had greater total vermilion area compared
      to both Korean groups. Finally, the Korean models had fuller lower and thinner
      upper vermilion areas than the nonmodels. CONCLUSIONS: Attractive lower facial
      portions in Caucasians are different from those of Koreans. Therefore, clinicians
      in Korea should use these data as guidelines for evaluating and enhancing
      patients' frontal facial esthetics.

PMID- 19582253
TI  - Creating certainty and confidence with indirect bonding.
AB  - Indirect bonding offers a superior method of adhering brackets to teeth, but few
      orthodontists use it. The neglect of this procedure has many origins, including
      expense, lack of expertise, and inconsistent results. This paper presents an
      indirect-bonding method that can be used to expedite bonding appointments and
      make them more pleasant for patients and clinicians alike.

PMID- 19582254
TI  - Prospective treatment analysis: are we planning adequately?
AB  - The orthodontic profession is experiencing a new era. The introduction of 3D
      imaging is revolutionizing orthodontic diagnostic philosophy. This philosophy
      emphasizes the importance of implementing the prospective treatment analysis
      concept and its triad of ERA, SA, and TA (End Result Analysis, Subtraction
      Analysis, and Treatment Analysis). The question is whether we have the
      armamentarium for this triad and if we are ready for PTA?

PMID- 19582255
TI  - Influence of straight-pull headgear on the eruption pattern of maxillary canines:
      a retrospective study.
AB  - AIM: To evaluate the effect of the straight-pull headgear and activator (Andresen
      type) treatment on the eruption pattern of impacted maxillary canines. METHODS:
      Mesiodistal positional, angular, and vertical changes of impacted canines were
      evaluated and statistically analyzed in pre- and posttreatment panoramic
      radiographs of 22 patients (12 treated with combination headgear, 10 treated with
      an activator). RESULTS: Eruption of the permanent canines in the group treated
      with straight-pull headgear was significantly more successful (88%) than in the
      group treated with an activator (62%). CONCLUSION: Mesiodistal and vertical crown
      position, as well as angulation of canines, differ significantly between subjects
      treated with straight-pull headgear or an activator.

PMID- 19582256
TI  - Open-bite treatment utilizing clear removable appliances with intermaxillary and
      intramaxillary elastics.
AB  - Clear removable appliances with elastics can be effective and efficient in
      extruding maxillary teeth during aligner treatment or following a relapse of an
      open bite. Some patients with open bites refuse to wear conventional fixed
      appliances. In these individuals, clear aligners with elastics could be a
      valuable alternative.

PMID- 19582257
TI  - Mixed-dentition analysis in a Turkish population.
AB  - OBJECTIVE: To study the reliability of the Tanaka-Johnston mixed-dentition
      analysis in Turkish individuals and develop a new population-adjusted regression
      equation for predicting the size of unerupted canines and premolars. The new
      regression equations were tested to establish their validity in Turkish children.
      METHODS: The mesiodistal dimensions of teeth on study casts of 12- to 14-year-old
      Turkish children were measured. The actual tooth measurements were then compared
      with predicted values using the Tanaka-Johnston equation. Subsequently, the new
      regression equations were tested in a group of 50 individuals to determine their
      validity. RESULTS: The Tanaka-Johnston regression equations overestimated the
      actual mesiodistal widths of permanent canines and premolars. With the new
      regression equations, no statistically significant differences were observed
      between actual and predicted widths. CONCLUSION: The Tanaka-Johnston prediction
      method is not accurate when applied to a Turkish population. The new equations
      are reliable for predicting the width of unerupted canines and premolars in
      Turkish individuals.

PMID- 19582258
TI  - The Damon System and release of substance P in gingival crevicular fluid during
      orthodontic tooth movement in adults.
AB  - Metabolism by peptidases plays an important role in modulating the levels of
      biologically active neuropeptides. One of these neuropeptides, substance P (SP),
      a component of gingival crevicular fluid (GCF), may exponentiate the inflammatory
      process during orthodontic tooth movement. The aim of this study was to
      investigate the GCF levels of SP in patients using different bracket systems.
      Subjects were 10 patients (four males, six females; mean age, 25.1 +/- 4.4 years)
      undergoing orthodontic movement (leveling) in the maxilla. Conventional brackets
      were placed on the left side, while the teeth on the right received self-ligating
      brackets. The teeth on the mandibular left side without any orthodontic
      attachments served as controls. GCF was sampled at 0, 1, 24, and 168 hours after
      initiation of treatment. Prevention of plaque-induced inflammation allowed
      assessment of the dynamics of mechanically stimulated SP levels in the GCF, which
      was determined using commercially enzyme-linked immunoabsorbent assay (ELISA)
      kits. GCF levels of SP for the Damon System sites were significantly lower than
      for the teeth with conventional brackets at 24 hours. This result indicates that
      the Damon System inhibited an increase in the amount of SP in the GCF. Thus, the
      Damon System is useful to reduce the inflammation and pain resulting from
      orthodontic forces.

PMID- 19582260
TI  - Orthodontics around the world: an interview with Prof Abdellatif Boughzala of
      Tunisia by Rainer-Reginald Miethke.

PMID- 19582259
TI  - A new sagittal dysplasia indicator: the YEN angle.
AB  - AIM: To develop a new cephalometric measurement to evaluate the sagittal
      relationship between the maxilla and mandible. MATERIAL AND METHODS: Seventy-five
      pretreatment lateral cephalograms (25 each of Class I, II, and III) were
      subdivided based on ANB, Wits appraisal, and Beta angle into skeletal Class I,
      II, and III. The same cephalograms were again classified into skeletal Class I,
      II, and III based purely on Beta angle. The new measurement is based on the
      landmarks S, M (midpoint of the anterior maxilla), and G (center at the bottom of
      the symphysis), which form the YEN angle measured at M. RESULTS: The mean and
      standard deviation for the YEN angle were calculated in all three skeletal
      groups. After using one-way analysis of variance (ANOVA) and Newman Keuls test,
      receiver-operating characteristic curves were obtained for the YEN angle in both
      types of classifications. The results showed that a patient with a YEN angle from
      117 to 123 degrees could be considered to have a Class I skeletal relationship.
      CONCLUSIONS: The YEN angle was developed to assess more reliably the sagittal
      relationship between both jaws. Subjects with a YEN angle between 117 and 123
      degrees have a skeletal Class I pattern. With an angle less than 117 degrees,
      patients are considered to have a skeletal Class II relationship, and with an
      angle greater than 123 degrees, patients have a skeletal Class III.

PMID- 19582262
TI  - Themed issue dedicated to Ester Oliveros on her 60th Birthday..

PMID- 19582263
TI  - Introduction to the themed issue in honour of Esther Oliveros.

PMID- 19582265
TI  - Physical and chemical quenching rates and their influence on stereoselective
      photooxygenation of oxazolidinone-functionalized enecarbamates.
AB  - Physical and chemical quenching rate constants were measured for the reaction of
      singlet oxygen with oxazolidinone-functionalized enecarbamates to investigate the
      role of vibrational deactivation in product stereoselectivity.

PMID- 19582264
TI  - Sensitized formation of oxidatively generated damage to cellular DNA by UVA
      radiation.
AB  - The survey is aimed at critically reviewing information on the UVA-mediated
      oxidative reactions to cellular components with emphasis on DNA as the result of
      mostly photosensitized pathways. It appears clearly that UVA radiation is
      relatively much more efficient than UVB photons in inducing oxidative processes.
      The main UVA-induced oxidative degradation pathways of DNA are reported and
      discussed mechanistically. They are mostly rationalized in terms of a major
      contribution of singlet molecular oxygen ((1)O(2)) and to a lesser extent of
      hydroxyl radical ( OH), that in the latter case originates from Fenton-type
      reactions. This leads to the predominant formation of 8-oxo-7,8-dihydroguanine
      together with smaller amounts of oxidized pyrimidine bases and DNA strand breaks
      in UVA-irradiated cells.

PMID- 19582266
TI  - Photoreactions of substituted o-cresyl acylates in cyclohexane and in
      polyethylene films. The influences of intra- and inter-molecular 'crowding'
      effects.
AB  - Photo-Fries rearrangements and associated photoreactions of four o-cresyl
      acylates were investigated in cyclohexane and in unstretched and stretched
      polyethylene (PE) films with different degrees of crystallinity. The esters
      differ in the number of phenyl substituents attached to the methyl group of the
      cresyl part and the length of the acyl chain. The influences of intramolecular
      structural factors and intermolecular environmental effects on the fates of the
      excited singlet states and the singlet state aryloxy/acyl radical pairs generated
      subsequently from them are explored. The results indicate that there are
      definable limits to the selectivity of the photoreactions of aryl esters that are
      dependent on their shapes and the ability of their environments to interact with
      them. Quantum yields for the reactions of the o-cresyl acylates were measured in
      cyclohexane and their values can be understood on the bases of a combination of
      conformational and electronic factors. The PE cavities holding the less
      globularly shaped o-cresyl acylates act as templates for the formation of the
      photoproducts: the ratios of the 2- and 4-position photo-Fries rearrangement
      products from o-cresyl acetate and 2-benzylphenyl acetate are higher when
      irradiated in films that are stretched or have higher film crystallinity; control
      by the PE cavities over the fates of the radical pairs is diminished for the o
      cresyl acylate with two phenyl groups appended to the methyl of the cresyl part.
      The cavities of the PE films exert an interesting influence on the ability of the
      excited singlet states to undergo concerted decarboxylation reactions as well.

PMID- 19582267
TI  - Water disinfection with Ru(II) photosensitisers supported on ionic porous
      silicones.
AB  - In this study we report on the preparation, photochemical characterisation and
      evaluation of the photodisinfection power of various new types of singlet oxygen
      photosensitising materials prepared from two homoleptic Ru(ii) complexes with
      polyazaheterocyclic ligands (abbreviated as RDP(2+) and RSD(4-)) immobilised on
      anionic and cationic porous silicone polymers (pSil(-) and pSil(+),
      respectively). Time-resolved emission measurements in the UV-Vis-NIR have
      confirmed high (1)O(2) production by these materials in water (tau(Delta) = 25-32
      micros) due to efficient quenching of the long-lived sensitiser triplet state by
      dissolved O(2), particularly in those pSil(-) materials with higher sensitiser
      load (P(O(2))(T)ca. 0.74 and 0.88 for 1.15 and 4.40 g m(-2), abbreviated as "M"
      and "H", respectively). Photodisinfection tests carried out using both a solar
      simulated lab-scale setup and under sunlight have demonstrated the strong
      bacteria inactivation ability of the RDP/pSil(-) material with the highest
      sensitiser load. Results of photochemical experiments with aqueous suspensions of
      Enterococcus faecalis at an initial concentration of 10(4) CFU mL(-1) yield
      average inactivation rates of 3200 and 24 000 CFU h(-1) for RSD/pSil(+) and H
      RDP/pSil(-) films, respectively. The sensitiser charge, its load on the polymer
      support and the ionic character of the silicone surface play an essential role on
      the singlet oxygen production in heterogeneous media, the stability of the
      resulting material, and on the interaction with bacteria, determining the
      microorganism inactivation efficiency of the ionic silicone-based
      photosensitising materials.

PMID- 19582268
TI  - Photophysics and photochemistry of rose bengal bound to human serum albumin.
AB  - Rose bengal (RB) readily binds to human serum albumin (HSA). At low RB
      concentrations, 90% of the dye is associated to the protein (5 microM), This
      association takes place in specific binding sites I and/or II. At higher RB
      concentrations, unspecific binding takes place with up to 10 RB molecules bound
      per protein molecule. The behavior of excited RB molecules bound to HSA is widely
      different to that observed in aqueous solution. Furthermore, the data also show
      that the behavior of bound RB molecules changes with the average number of dye
      molecules per protein (n). In particular, when n is large, the fluorescence yield
      is significantly reduced and no measurable long-lived triples and free singlet
      oxygen formation from bound dyes is detected. These results are related to self
      quenching of the singlet and, most likely, excited triplets. All results point to
      the relevance of intra-protein generated singlet oxygen. However, when the dye is
      bound to the protein, at low oxygen concentrations such as those prevailing in
      vivo, trapping by oxygen of the triplet becomes inefficient and type I processes
      could contribute to the observed photoprocesses.

PMID- 19582269
TI  - Oxidation of polystyrene aerosols by VUV-photolysis and/or ozone.
AB  - Aerosols of submicron polystyrene particles were oxidized by either vacuum
      ultraviolet (VUV) irradiation in the presence of molecular oxygen (O(2)) and/or
      by ozone (O(3)). Different degrees of oxidation and oxidative degradation were
      reached by VUV-photolysis depending on radiant energy, O(2) and H(2)O
      concentrations in the bulk gas mixture as well as on particle diameter. The same
      functionalization was obtained by exposing the aerosol to O(3), however,
      oxidation, in particular oxidative degradation, was less efficient. The evolution
      of hydroxyl and carbonyl functions introduced was quantified by ATR-FTIR
      spectroscopy of filtered particles, and oxidative degradation of the polymer
      particles was confirmed by determining size and number of aerosol particles
      before and after oxidation. Efficiency analyses are based on the results of an
      O(3) actinometry and on an evaluation of the rate of absorbed photons by the
      aerosol particles in function of their size.

PMID- 19582270
TI  - Kinetics of nitrobenzene and 4-nitrophenol degradation by UV irradiation in the
      presence of nitrate and nitrite ions.
AB  - In the present work we analyze the degradation rates of nitrobenzene (NBE) and 4
      nitrophenol (PNP), by using UV irradiation in the presence of HNO(2)/NO(2)(-) or
      NO(3)(-) added as sources of hydroxyl radicals. With both nitroaromatic
      substrates pseudo-first-order kinetics were observed for conversion degrees of at
      least 45% within the analyzed experimental domain. The apparent rate constants
      (k(app)) were higher for UV/NO(3)(-) systems than for UV/HNO(2)/NO(2)(-) systems
      at high additive concentrations, whereas the opposite trend was observed for low
      additive concentrations. In addition, k(app) values were found to decrease with
      increasing substrate concentration. The analysis of the distribution of the most
      important products detected by HPLC suggests that reactions involving nitrogen
      species are likely to play a secondary role in the apparent rate constants
      measured. NBE and PNP degradation rates induced by HNO(2)/NO(2)(-) photolysis
      increase to a maximum value and then decrease with increasing additive
      concentration. On the other hand, substrate degradation rates increase with
      NO(3)(-) concentrations until a plateau is reached, but no decrease of k(app) is
      observed even at very high additive concentrations. The results may be
      quantitatively described by a simplified model that considers two opposite
      effects. On the one hand, the increase of additive concentrations increases the
      amount of photons absorbed by the photoactive species in both systems. On the
      other hand, high additive concentrations significantly decrease the degradation
      rates in UV/HNO(2)/NO(2)(-) systems where HNO(2) and NO(2)(-) are efficient
      hydroxyl radical scavengers, whereas this decrease is not observed in UV/NO(3)(-)
      systems since the scavenging ability of NO(3)(-) is much lower. Inner filter and
      scavenging effects are discussed and the results are compared with the ones
      previously reported for UV/H(2)O(2) systems.

PMID- 19582271
TI  - Photolysis of an asymmetrically substituted diazene in solution and in the
      crystalline state.
AB  - In this work we study the product distribution in the steady state photolysis of
      a diazene, (1-biphenyl-4-yl-1-methyl-ethyl)-tert-butyl diazene, and a ketone, 2,4
      bis(biphenyl-4-yl)-2,4-dimethyl-pentan-3-one, in the solid state and in solution.
      The two compounds yield 1-biphenyl-4-yl-1-methyl-ethyl (BME ) radicals upon
      photolysis. The ketone yields two units of this radical, whereas the diazene
      yields one BME and one tert-butyl radical. Product analysis of the two compounds
      in solution makes it possible to differentiate their origin from their
      corresponding geminate cages, and from the different encounter pairs in the case
      of the asymmetrically substituted diazene photolysis. In this way we obtain a
      complete reaction scenery for the diazene, a compound with interesting features
      as a radical photoinitiator and as a cage effect probe in fluid media. The
      reaction in cages containing two BME radicals shows a decrease by a factor of 4
      in the ratio of combination to disproportionation products upon going from the
      solid to the liquid phase. On the contrary, the reaction in cages containing a
      BME and a tert-butyl radical shows a 30-fold increase in combination to
      disproportionation ratio in liquid compared to the crystal. We analyze the
      reasons for these differences considering the differences in the reactivity of
      the radicals and in cage rigidity.

PMID- 19582272
TI  - Solvent effect on the UV/Vis absorption and fluorescence spectroscopic properties
      of berberine.
AB  - Spectral and photophysical properties of the alkaloid berberine (B) were studied
      in solvents with different solvent parameters, using UV/Vis absorption, emission
      and excitation spectroscopy. The absorption and emission maxima were found to be
      between 421-431 nm and 514-555 nm, respectively, leading to Stokes' shifts
      between 4099 and 5735 cm(-1). The fluorescence quantum yields varied between 10(
      2)-10(-4), depending on the solvent. Different solvent scales have been used to
      study the solvatochromism of B. Linear solvation energy relationships (LSER)
      proposed by Kamlet-Taft suggest that B is a molecule attractive as a probe for
      solvent polarity and hydrogen bonding properties.

PMID- 19582273
TI  - Heterogeneous photocatalytic degradation of gallic acid under different
      experimental conditions.
AB  - UV/TiO(2)-heterogeneous photocatalysis was tested as a process to degrade gallic
      acid (Gal) in oxygenated solutions at pH 3. In the absence of oxidants other than
      oxygen, decay followed a zero order rate at different concentrations and was slow
      at concentrations higher than 0.5 mM. Addition of Fe(3+), H(2)O(2) and the
      combination Fe(3+)/H(2)O(2) improved Gal degradation. In the absence of H(2)O(2),
      an optimal Fe : Gal molar ratio of 0.33 : 1 was found for the photocatalytic
      decay, beyond which addition of Fe(3+) was detrimental and even worse in
      comparison with the system in the absence of Fe(3+). TiO(2) addition was
      beneficial compared with the same system in the absence of the photocatalyst if
      Fe(3+) was added at low concentration (0.33 : 1 Fe : Gal molar ratio), while at
      high concentration (1 : 1 Fe : Gal molar ratio) TiO(2) did not exert any
      significant effect. H(2)O(2) addition (1 : 0.33 Gal : H(2)O(2) molar ratio,
      absence of Fe(iii)) also enhanced the heterogeneous photocatalytic reaction.
      Simultaneous addition of Fe(3+) and H(2)O(2) was more effective than the addition
      of the separate oxidants. This system was compared with Fenton and photo-Fenton
      systems. At low H(2)O(2) concentration (0.33 : 1 : 0.2 Fe : Gal : H(2)O(2) molar
      ratio), the presence of TiO(2) also enhanced the reaction. The influence of the
      thermal charge transfer reaction between Gal and Fe(iii), which leads to an
      important Gal depletion in the dark with formation of quinones, was analysed. The
      mechanisms taking place in these complex systems are proposed, paying particular
      attention to the important charge transfer reaction of the Fe(iii)-Gal complex
      operative in dark conditions.

PMID- 19582274
TI  - Photolysis of ferric ions in the presence of sulfate or chloride ions:
      implications for the photo-Fenton process.
AB  - The photo-Fenton process (Fe(2+)/Fe(3+), H(2)O(2), UV light) is one of the most
      efficient and advanced oxidation processes for the mineralization of the organic
      pollutants of industrial effluents and wastewater. The overall rate of the photo
      Fenton process is controlled by the rate of the photolytic step that converts
      Fe(3+) back to Fe(2+). In this paper, the effect of sulfate or chloride ions on
      the net yield of Fe(2+) during the photolysis of Fe(3+) has been investigated in
      aqueous solution at pH 3.0 and 1.0 in the absence of hydrogen peroxide. A kinetic
      model based on the principal reactions that occur in the system fits the data for
      formation of Fe(2+) satisfactorily. Both experimental data and model prediction
      show that the availability of Fe(2+) produced by photolysis of Fe(3+) is
      inhibited much more in the presence of sulfate ion than in the presence of
      chloride ion as a function of the irradiation time at pH 3.0.

PMID- 19582275
TI  - A combined theoretical and experimental study on the oxidation of fulvic acid by
      the sulfate radical anion.
AB  - The kinetics of the reaction of sulfate radicals with the IHSS Waskish peat
      fulvic acid in water was investigated in the temperature range from 289.2 to
      305.2 K. The proposed mechanism considers the reversible binding of the sulfate
      radicals by the fulvic acid. The kinetic analysis of the data allows the
      determination of the thermodynamic parameters DeltaG degrees = -10.2 kcal mol(
      1), DeltaH degrees = -16 kcal mol(-1) and DeltaS degrees = -20.3 cal K(-1) mol(
      1) for the reversible association at 298.2 K. Theoretical (DFT) calculations
      performed with the Buffle model of the fulvic acids support the formation of H
      bonded adducts between the inorganic radicals and the humic substances. The
      experimental enthalpy change compares well with the theoretical values found for
      some of the investigated adducts.

PMID- 19582276
TI  - Light and dark biocidal activity of cationic poly(arylene ethynylene) conjugated
      polyelectrolytes.
AB  - In this paper we report a study of cationic poly(arylene ethynylene) conjugated
      polyelectrolytes. The objective of the study was to compare the behavior of a
      polymer where a thiophene has replaced a phenyl ring in poly(phenylene
      ethynylene) polycations (PPE) previously investigated. Properties of solution
      phase and physisorbed suspensions of the polymer on microspheres were
      investigated. The photophysical properties of the polymer are evaluated and used
      to understand the striking differences in biocidal activity compared to the PPE
      polymers previously examined. The principal findings are that the thiophene
      polymer has remarkable dark biocidal activity against Pseudomonas aeruginosa
      strain PAO1 but very little light-activated activity. The low light-activated
      biocidal activity of the thiophene polymer is attributed to a highly aggregated
      state of the polymer in aqueous solutions and on microspheres as a physisorbed
      coating. This results in low triplet yields and a very poor sensitization of
      singlet oxygen and other reactive oxygen intermediates. The highly effective dark
      biocidal activity of the thiophene-containing polymers is attributed to its high
      lipophilicity and the presence of accessible quaternary ammonium groups. The
      difference in behavior among the polymers compared provides insights into the
      mechanism of the dark process and indicates that aggregation of polymer can
      reduce light activated biocidal activity by suppressing singlet oxygen
      generation.

PMID- 19582277
TI  - Photophysics and stability of cyano-substituted boradiazaindacene dyes.
AB  - The solvatochromic photophysical properties of two fluorescent, cyano-substituted
      BODIPY dyes-8-(4-bromophenyl)-3,4,4,5-tetracyano-4-bora-3a,4a-diaza-s-indacene
      (4CN) and 8-(4-bromophenyl)-3,5-dicyano-4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (2CN)-have been studied in various solvents by UV-vis spectrophotometry
      and steady-state and time-resolved fluorometry. These two BODIPY analogues have
      comparable photophysical properties, implying that displacement of F by CN at
      boron has a negligible effect. Both compounds have high fluorescence quantum
      yields Phi(f) (0.65-0.90 for 4CN and 0.63-0.88 for 2CN) in the solvents studied
      and display mono-exponential fluorescence decay profiles in nonprotic solvents. A
      new, generalized treatment of the solvent effect based on four mutually
      independent, empirical solvent scales (dipolarity, polarizability, acidity, and
      basicity of the medium) indicates that solvent polarizability and, to a lesser
      degree, solvent (di)polarity are crucial factors causing the solvent-dependent
      shifts of the UV-vis absorption and fluorescence emission. The rate constants of
      radiative deactivation (k(f)) are nearly independent of the nonprotic solvent
      [k(f) = (1.4 +/- 0.1) x 10(8) s(-1) for 4CN and (1.5 +/- 0.2) x 10(8) s(-1) for
      2CN]. Both compounds undergo a color change in polar aprotic solvents (acetone,
      acetonitrile, and N,N-dimethylformamide), which can be stopped by addition of
      HClO(4). The kinetics of this color change indicates that the decomposition of
      these cyano-substituted BODIPY compounds is complex.

PMID- 19582279
TI  - Optimisation of the chemical generation of singlet oxygen (1O2, 1Deltag) from the
      hydrogen peroxide-lanthanum(III) catalytic system using an improved NIR
      spectrometer.
AB  - A near-IR chemiluminescence spectrometer designed to study chemical sources of
      singlet oxygen ((1)O(2), (1)Delta(g)), was built by coupling a reactor
      compartment to a nitrogen-cooled Ge diode through a bundle of optical fibres.
      This device was used to optimise the generation of (1)O(2) from the hydrogen
      peroxide-lanthanum(iii) catalytic system. The reaction kinetics were studied with
      a 2(3)3(3)//12 screening experimental design comprising twelve experiments. The
      influence of six factors was examined: the nature of the lanthanum salt
      (hydroxide, oxide or nitrate) and its concentration (0.05 or 0.1 mol L(-1)), the
      pH value (5, 7 or 9), the concentration of H(2)O(2) (0.5, 1 or 2 mol L(-1)), the
      temperature (20 or 30 degrees C) and the concentration of EDTA (0 or 5 mmol L(
      1)). Two responses were measured: the rate of H(2)O(2) disproportionation and the
      intensity of the luminescence of (1)O(2) at 1270 nm. The essential factor is the
      nature of the lanthanum salt since La(NO(3))(3) induces the disproportionation of
      H(2)O(2) about 60 x faster than La(2)O(3) or La(OH)(3). Other influencing factors
      are the pH value, the concentration of H(2)O(2), the temperature and the
      concentration of the lanthanum salt whereas the concentration of EDTA has no
      effect on the reaction. The catalytic activity of La(NO(3))(3) was then
      investigated in further detail by studying the influence of two factors (pH and
      [H(2)O(2)]) thanks to a Doehlert design.

PMID- 19582278
TI  - Reactivity of hydroxyl radicals with neonicotinoid insecticides: mechanism and
      changes in toxicity.
AB  - The reactivity of hydroxyl radicals (HO ) towards three neonicotonoid
      insecticides, namely imidacloprid, thiacloprid and acetamiprid was investigated.
      These radicals were generated by photolysis of H(2)O(2) solutions. Flash
      photolysis experiments were used to determine the rate constants of 5.5 x 10(10)
      M(-1)s(-1), 6 x 10(10) M(-1)s(-1), and 7.5 x 10(10) M(-1)s(-1), for the reactions
      of HO with acetamiprid, imidacloprid, and thiacloprid, respectively. Continuous
      irradiation experiments in the absence and presence of H(2)O(2) allowed the
      identification and toxicity evaluation of the primary photo- and oxidation
      products of the insecticides. In all cases, the less toxic 6-chloronicotinic acid
      was found to be the major product at higher degrees of oxidation. The results
      reported here indicate that the half life of the insecticides due to their
      reaction with HO radicals in natural aquatic reservoirs may vary between 5 h and
      19 days, and therefore the hydroxyl radical-mediated oxidation may be a
      significant abiotic elimination route. However, elimination of the insecticide
      under such conditions might not improve the quality of the contaminated water, as
      the primary products of degradation still show considerable toxicity to Vibrio
      fischeri assays.

PMID- 19582280
TI  - Application of solar advanced oxidation processes to the degradation of the
      antibiotic sulfamethoxazole.
AB  - This work deals with the treatment of highly concentrated sulfamethoxazole (SMX)
      solutions by some advanced oxidation processes (AOPs) that have not been studied
      until now. The antibiotic has been subjected to oxidation by photolysis,
      UV/H(2)O(2) and photo-Fenton using both artificial light and sunlight as
      radiation sources depending on the installation scale. SMX, total organic carbon
      (TOC) and chemical oxygen demand (COD), as well as the generation of NH(4)(+),
      NO(3)(-) and SO(4)(2-), were followed. SMX photolytic degradation efficiency
      followed the ranking: 254 nm lamps > sunlight > black-light blue (BLB) lamps
      (negligible for the latter). The highest eliminations were obtained by means of
      UV/H(2)O(2) reaction in a lab-scale reactor (254 nm lamps) with an initial
      H(2)O(2) concentration of 200 mg L(-1): DeltaTOC = 62.3%; DeltaCOD = 79.1% (more
      than 6 h). Similar removals were achieved with a lab-scale photo-Fenton reactor
      (BLB lamps) but using 400 mg L(-1) of oxidant (94 min). The use of solar light
      appeared to be an interesting option since satisfactory results were obtained in
      the solar-based photo-Fenton experiments compared to the lab-scale ones, and also
      since a significant improvement with respect to the solar photolysis was achieved
      when performing the UV/H(2)O(2) reaction with sunlight. Finally, some of the
      resultant effluents from different reactions were subjected to a short-term
      biodegradability test in order to estimate their quality from a biological point
      of view.

PMID- 19582281
TI  - Photocatalytic efficiencies of self-cleaning glasses. Influence of physical
      factors.
AB  - Two commercial types of self-cleaning glass (SCG) have been tested to confirm the
      real photocatalytic nature of their properties. This was done by using four
      photocatalytic tests: (i) in the gas phase with the total oxidation of acetylene;
      (ii) in water with the total degradation of malic acid, (iii) in water with the
      total degradation of methylene blue, and (iv) in the solid phase with the total
      oxidative degradation of a layer of stearic acid deposited on the self-cleaning
      glass surface, in contact with the superficial titania coating. The influence of
      various factors (temperature, humidity, wavelength, radiant flux, presence of
      inorganic particles stuck at the glass surface) was explained in line with the
      fundamentals of photocatalysis. The results helped to understand the behaviour of
      self-cleaning glass.

PMID- 19582282
TI  - The local and observed photochemical reaction rates revisited.
AB  - In a broad sense, photochemical reactions proceed through pathways involving
      several reaction steps. The initiation step is the absorption of energy both by
      the reactant or sensitizer molecules and in some cases, by the catalyst, leading
      to intermediate products that ultimately give rise to stable end products.
      Preferably, the reaction rate expression is derived from a proposed mechanism
      together with sound simplifying assumptions; otherwise, it may be adopted on an
      empirical basis. Under a kinetic control regime, the rate expression thus
      obtained depends on the local rate of photon absorption according to a power law
      whose exponent very often ranges from one half to unity. The kinetic expression
      should be valid at every point of the reactor volume. However, due to radiation
      attenuation in an absorbing and/or scattering medium, the value of the photon
      absorption rate is always a function of the spatial position. Therefore, the
      overall photochemical reaction rate will not be uniform throughout the entire
      reaction zone, and the distinction between local and volume average photochemical
      reaction rates becomes mandatory. Experimental values of reaction rates obtained
      from concentration measurements performed in well-mixed reaction cells are,
      necessarily, average values. Consequently, for validation purposes, experimental
      results from these cells must be compared with volume averages of the
      mechanistically or empirically derived local reaction rate expressions. In this
      work it is shown that unless the rate is first order with respect to the photon
      absorption rate or the attenuation in the absorbing and/or scattering medium is
      kept very low, when the averaging operation is not performed, significant errors
      may be expected.

PMID- 19582283
TI  - Photoinduced degradation of 2,4-dichlorophenol in water: influence of various
      Fe(III) carboxylates.
AB  - Fe(III)-carboxylate complexes were investigated with respect to tri-carboxylic
      (citric), di-carboxylic (tartaric) and mono-carboxylic (pyruvic) acids. In
      agreement with the chemical structure, results demonstrated that Fe(iii) was
      complexed by citric acid with a ratio of 1 : 1 (Fe/ligand), tartaric acid (d or
      l) with a ratio of 1 : 2 and by pyruvic acid with a ratio of 1 : 3. The iron
      concentration was fixed at 0.3 mmol L(-1) and the ligand concentration ranged
      from 0 to 1.0 mmol L(-1). The primary stage of 2,4-dichlorophenol (2,4-DCP)
      degradation photoinduced by these Fe(iii) complexes was investigated under
      monochromatic irradiation (lambda = 365, 313 and 296 nm). The values of initial
      quantum yields of 2,4-DCP disappearance (between 0.01 and 0.135) and Fe(ii)
      formation (between 0.002 and 0.47) were evaluated and are presented in detail.
      Short irradiation wavelength (296 nm), low pH (3.0) and high oxygen concentration
      favoured the pollutant degradation. The disappearance of 2,4-DCP was complete
      under these favourable conditions.

PMID- 19582284
TI  - Fulvic acid-mediated phototransformation of mecoprop. A pH-dependent reaction.
AB  - Elliott soil fulvic acid sensitized the phototransformation of mecoprop in
      aqueous medium. The reaction was selective, leading to the main formation of 4
      chloro-2-methylphenol in aerated and in deoxygenated neutral solution. In turn, 4
      chloro-2-methylphenol underwent a fulvic acid-mediated phototransformation. A pH
      decrease from 8 to 2.2 led to an increase of the rate of mecoprop loss by a
      factor of 10. The roles of hydroxyl radicals, fulvic triplets and singlet oxygen
      were investigated using the scavenging technique. At pH 6.5 where mecoprop was in
      the anionic form, triplet excited states and hydroxyl radicals were the main
      oxidant species contributing to 40 +/- 10% and 20 +/- 5% of the reaction,
      respectively. At pH 2.2 where mecoprop was protonated, fulvic triplets and
      hydroxyl radicals contributed to 75 +/- 10% and 16 +/- 5%, respectively. The
      enhancement of the reaction upon acidification might result from two phenomena
      tending to the same effect: (i) the capacity of protonated MCP to reach intra
      humic microdomains and there interact with reactive species, and (ii) a greater
      photosensitizing property of FA in acidic medium.

PMID- 19582290
TI  - Enantioselective metal-catalyzed activation of strained rings.
AB  - Activation of otherwise inert bonds has significant potential in the design of
      efficient and synthetically useful transformations. While general catalytic
      carbon-carbon single bond activations are still in their infancy, this emerging
      area examines recent developments in the activation of strained rings, focusing
      on enantioselective reactions.

PMID- 19582291
TI  - Recent highlights in the synthesis of highly functionalized pyrimidines.
AB  - The pyrimidine scaffold represents an important pharmacophore endowed with a wide
      range of pharmacological activities according to the specific decoration of the
      heterocycle. This perspective article will briefly outline the most interesting
      approaches recently reported for the synthesis of highly functionalized
      pyrimidine derivatives.

PMID- 19582292
TI  - Efficient syntheses of phosphonylated isochromenes by regioselective 6-endo-dig
      addition to carbon-carbon triple bond catalyzed by Pd(OAc)2.
AB  - Palladium(II)-catalyzed cycloisomerization of [(2
      alkynylphenyl)hydroxymethyl]phosphonates 6 provides an efficient route to
      phosphonylated isochromenes 7 in THF at room temperature and the reaction
      proceeded in a regioselective manner leading to the 6-endo-dig products 7 in
      moderate to excellent yields.

PMID- 19582293
TI  - Size-dependent cation transport by cyclic alpha-peptoid ion carriers.
AB  - N-Benzyloxyethyl macrocyclic peptoids 3 and 4 were synthesized and subjected to
      alkali metal binding studies; these compounds, plus the known 1 and 2, when
      subjected to ion transport studies, demonstrated size-dependent selectivity for
      the first group alkali metals cation transport.

PMID- 19582294
TI  - Porphyrin-linked nitroimidazole antibiotics targeting Porphyromonas gingivalis.
AB  - Periodontal disease is an inflammatory process affecting supporting tissues
      surrounding the teeth. The anaerobic gram-negative bacterium Porphyromonas
      gingivalis is implicated in the disease. This organism requires the uptake of
      porphyrins most apparently as haem 1 from local haemorrhage and it has a HA2
      receptor on the outer membrane for this purpose that provides the opportunity to
      achieve selective anti-microbial activity. Uniquely, this receptor is based on
      recognition of porphyrin macrocycle and on a propionic acid side-chain rather
      than recognition of the coordinated metal ion through chelation, a process used
      by other organisms with the HasA porphyrin receptor. Porphyrin-antibiotic
      conjugates 11, 12, 13a and 13b were designed as potential highly selective P.
      gingivalis inhibitors, a key point being that they are based on the use of free
      base porphyrins to render them unpalatable to other organisms. These compounds
      were synthesised from metronidazole 4 and deuteroporphyrin IX 3. Conjugates 11,
      12, 13a and 13b are all recognised by the HA2 receptor of P. gingivalis, bind as
      strongly as haem 1 to HA2 and are highly effective. For example, the amide-linked
      mono-metronidazole mono-acid adducts 11 and 12 have the same growth inhibitory
      activity towards P. gingivalis and both are two-fold more active than
      metronidazole 4 and ten- to twenty-fold more effective than the metronidazole
      derivative, amine 5. The methyl esters 9 and 10, in contrast, are not recognised
      by HA2 and are ineffective in inhibiting P. gingivalis, leading to the conclusion
      that capture by HA2 may be necessary for activity of the adducts. Preliminary
      growth inhibition assays involving a range of bacteria have demonstrated the high
      selectivity of conjugates 13a and 13b towards P. gingivalis.

PMID- 19582295
TI  - Exclusive platination of loop adenines in the human telomeric G-quadruplex.
AB  - The present article reports on the platination of the human telomeric G
      quadruplex by three Pt-terpyridine complexes. It is shown that extension of the
      aromatic surface of the terpyridine moiety surrounding the platinum atom
      influences both the binding affinity and the platination activity. Remarkably,
      the most strongly bound complex Pt-ttpy coordinates exclusively the adenine
      nucleobases present in the loop of the G-quadruplex. This exclusive single-site
      platination reflects the interaction of the compound with both the G-tetrad and
      the loop residues. In addition Pt-ttpy showed promising antiproliferative
      activity on a panel of cancer cell lines in a parallel study using cisplatin
      derivatives currently in clinical use.

PMID- 19582296
TI  - Peptide bond mimicry by (E)-alkene and (Z)-fluoroalkene peptide isosteres:
      synthesis and bioevaluation of alpha-helical anti-HIV peptide analogues.
AB  - The alpha-helix structures of the anti-HIV fusion inhibitory peptides are
      stabilized by the amino acid sequence and by intrachain hydrogen bonds. The study
      of peptide analogues using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres
      demonstrated the substantial, yet position-dependent, contribution of hydrogen
      bonds to the alpha-helix stability and anti-HIV bioactivity.

PMID- 19582297
TI  - Dynamic polythioesters via ring-opening polymerization of 1,4-thiazine-2,5
      diones.
AB  - We describe the preparation and characterization of polythioesters composed of
      alternating alpha-amino acid and alpha-thioglycolic acid residues that undergo
      dynamic constitutional exchange under mild conditions. The polymers are assembled
      via reversible ring-opening polymerizations of 1,4-thiazine-2,5-diones and
      related monomers in solution-phase conditions that do not require the use of
      transition metal catalysts. Because 1,4-thiazine-2,5-diones can be derived in
      part from alpha-amino acids, a variety of side chain functionalized monomers in
      optically pure forms could readily be accessed. In addition, the resulting
      polythioesters have the potential for intra- and inter-chain hydrogen bonding,
      which is known to impart materials properties to other previously studied
      polyamides. The studies reported here could be useful in advancing a new class of
      biodegradable polymers and furthermore suggest that dynamic constitutional
      exchange could be exploited to modify many known synthetic and natural
      polythioesters.

PMID- 19582298
TI  - Stabilizing unusual conformations in small peptides and glucopeptides using a
      hydroxylated cyclobutane amino acid.
AB  - The synthesis and the conformational study in the solid state and in aqueous
      solution of a peptide and a glucopeptide containing the non-natural (1S,2S)-1
      amino-2-hydroxycyclobutanecarboxylic acid (c(4)Ser) residue are reported. This is
      the first example of a glycopeptide containing a carbohydrate moiety linked to an
      underlying non-natural amino acid residue. The conformational analysis in
      solution combines NOEs and coupling constants data with Molecular Dynamics (MD)
      simulations with time-averaged restraints. The study reveals that the c(4)Ser-Ala
      Ala diamide peptide shows a conformation of two consecutive beta-turn type III
      structures (the basic structural element of a 3(10) helix). However, none of the
      turns observed in the peptide are present in the derived glucopeptide. The
      influence of the carbohydrate moiety on the peptide backbone can be explained by
      means of the existence of two simultaneous hydrogen bonds, between the endocyclic
      oxygen of the glucose and two amidic protons of the peptide. In addition, the non
      natural residue favors the existence of an unusual high energy conformation for
      the glycosidic linkage, the so-called anti-phi conformation.

PMID- 19582299
TI  - O-acyl isopeptide method: efficient synthesis of isopeptide segment and
      application to racemization-free segment condensation.
AB  - We report the establishment of the O-acyl isopeptide method-based racemization
      free segment condensation reaction toward future chemical protein synthesis.
      Peptide segments containing C-terminal O-acyl Ser/Thr residues were successfully
      synthesized by use of a lower nucleophilic base cocktail for Fmoc removal, and
      then coupled to an amino group of a peptide-resin without side reactions or
      epimerization. We also succeeded in performing the segment condensation in a
      sequential manner and in solution phase conditions as well.

PMID- 19582300
TI  - Peptide-nucleic acids (PNAs) with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)
      tetraone (PPT) as a universal base: their synthesis and binding affinity for
      oligodeoxyribonucleotides.
AB  - Peptide-nucleic acids (PNAs) including pyrimido[4,5-d]pyrimidine-2,4,5,7
      (1H,3H,6H,8H)-tetraone (PPT) as a nucleobase were synthesized, and their binding
      affinity for the complementary oligodeoxyribonucleotides was investigated. We
      found that PNAs with one or two PPT(s) and natural nucleobases (i.e., adenine,
      cytosine, guanine, or thymine) have excellent binding affinity for
      oligodeoxyribonucleotides with complementary bases at the positions facing the
      natural nucleobases, and with adenine, cytosine, guanine, and thymine at the
      positions opposite PPT in PNAs. The binding affinity of the PPT-containing PNA is
      higher than or comparable to that of a PNA consisting of all complementary
      natural nucleobases, viz. a PNA with a suitable natural nucleobase in place of
      PPT in the PPT-containing PNA. Consequently, it was concluded that PPT serves as
      a useful universal base that can recognize all natural nucleobases.

PMID- 19582301
TI  - Stereocontrolled synthesis of orthogonally protected 2-substituted 4
      aminopiperidines.
AB  - Expedient and highly stereoselective routes to orthogonally protected chiral 2
      substituted 4-aminopiperidines have been developed. Diastereoselective
      nucleophilic substitution of the hydroxy group of (2R,4S)-2-[(S)-1,2
      dibenzyloxyethyl]-4-hydroxy-1-[(S)-1-phenylethyl]piperidine using sodium azide
      afforded the corresponding azido derivative, which could be reduced and
      selectively protected to give (2R,4R)-1-tert-butoxycarbonyl-2-[(S)-1,2
      dibenzyloxyethyl]-4-acetylaminopiperidine. This compound was easily converted
      into optically active 2-substituted 4-aminopiperidines using different synthetic
      methodologies such as epoxide nucleophilic ring opening reactions and Wittig
      olefination reactions among others.

PMID- 19582302
TI  - Concurrent primary and secondary deuterium kinetic isotope effects in
      anilinolysis of O-aryl methyl phosphonochloridothioates.
AB  - The nucleophilic substitution reactions of Y-O-aryl methyl
      phosphonochloridothioates with substituted anilines (XC(6)H(4)NH(2)) and
      deuterated anilines (XC(6)H(4)ND(2)) are investigated kinetically in acetonitrile
      at 55.0 degrees C. The Hammett and Bronsted plots for substituent (X) variations
      in the nucleophiles are biphasic concave downwards with a break region between X
      = H and 4-Cl. The deuterium kinetic isotope effects (DKIEs) are primary normal
      (k(H)/k(D) = 1.03-1.30) for stronger nucleophiles (X = 4-MeO, 4-Me and H), and
      extremely large secondary inverse (k(H)/k(D) = 0.367-0.567) for weaker
      nucleophiles (X = 4-Cl, 3-Cl and 3-NO(2)). The cross-interaction constants are
      negative (rho(XY(H)) = -0.95 and rho(XY(D)) = -1.11) for stronger nucleophiles,
      while positive (rho(XY(H)) = +0.77 and rho(XY(D)) = +0.21) for weaker
      nucleophiles. These kinetic results indicate that the mechanism changes from a
      concerted process involving frontside nucleophilic attack for stronger
      nucleophiles to a stepwise process with a rate-limiting leaving group expulsion
      from the intermediate involving backside attack for weaker nucleophiles. A
      hydrogen-bonded, four-center-type transition state (TS) is suggested for a
      frontside attack, while a trigonal bipyramidal pentacoordinate TS is suggested
      for a backside attack. The unusually small DKIEs, as small as or equal to 0.4,
      for weaker nucleophiles seem to be ascribed to severe steric congestion in the
      TS.

PMID- 19582303
TI  - Synergy between chemo- and bio-catalysts in multi-step transformations.
AB  - Cascade synthetic pathways, which allow multi-step conversions to take place in
      one reaction vessel, are crucial for the development of biomimetic, highly
      efficient new methods of chemical synthesis. Theoretically, the complexity
      introduced by combining processes could lead to an improvement of the overall
      process; however, it is the current general belief that it is more efficient to
      run processes separately. Inspired by natural cascade procedures we successfully
      combined a lipase catalyzed amidation with palladium catalyzed coupling
      reactions, simultaneously carried out on the same molecule. Unexpectedly, the bio
      and chemo-catalyzed processes show synergistic behaviour, highlighting the
      complexity of multi-catalyst systems.

PMID- 19582304
TI  - A simple method for C-6 modification of guanine nucleosides.
AB  - A facile method for the introduction of various substituents at the C-6 position
      of guanosine and 2'-deoxyguanosine is reported. In a simple, 1-step
      transformation, tert-butyldimethylsilyl protected guanosine and 2'-deoxyguanosine
      were converted to the O(6)-(benzotriazol-1-yl) derivatives via reaction with 1H
      benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and
      1,8-diazabicyclo[5.4.0]undec-7ene (DBU). The easily isolated, stable and
      storable, O(6)-(benzotriazol-1-yl) guanosine derivatives upon exposure to a range
      of nucleophiles, under appropriate conditions, led to the C-6 modified 2-amino
      purine nucleoside analogues in good yields.

PMID- 19582305
TI  - Self-cleavable chemiluminescent probes suitable for protease sensing.
AB  - A new generation of dioxetane-based chemiluminescent substrates suitable for
      detecting protease activities is described. Our strategy involves the use of a
      self-cleavable spacer as the key molecular component of these protease-sensitive
      chemiluminescent probes. Among the assayed strategies, the PABA (para
      aminobenzylic alcohol) linker associated with an ether linkage enables the
      release of the light-emitting phenolic 1,2-dioxetane moiety through an enzyme
      initiated domino reaction. To validate this strategy, two proteolytic enzymes
      were chosen: penicillin amidase and caspase-3, and the corresponding self
      cleavable chemiluminescent substrates were synthesised. Their evaluation using an
      in vitro assay has enabled us to prove the decomposition of the linker under
      physiological conditions and the selectivity for the targeted enzyme.

PMID- 19582306
TI  - Kinetics and mechanism of thermal decomposition of kynurenines and biomolecular
      conjugates: ramifications for the modification of mammalian eye lens proteins.
AB  - Thermal degradation reactions of kynurenine (KN), 3-hydroxykynurenine (3OHKN),
      and several adducts of KN, to amino acids and reduced glutathione (GSH) have been
      studied at physiological temperature. These compounds are all implicated in age
      related mammalian eye lens cataract formation at the molecular level. The main
      reaction pathway for both KN and 3OHKN is deamination via beta-elimination to
      carboxyketoalkenes CKA and 3OHCKA. These reactions show a weak pH dependence
      below pH values of approximately 8, and a strong pH dependence above this value.
      The 3OHKN structure deaminates at a faster rate than KN. A mechanism for the
      deamination reaction is proposed, involving an aryl carbonyl enol/enolate ion,
      that is strongly supported by the structural, kinetic, and pH data. The
      degradation of Lys, His, Cys and GSH adducts of the CKA moieties was also
      studied. The Lys adduct was found to be relatively stable over 200 h at 37
      degrees C, while significant degradation was observed for the other adducts. The
      results are discussed in terms of known post-translational modification reactions
      of the lens proteins and compared to incubation studies involving KN and related
      compounds in the presence of proteins.

PMID- 19582307
TI  - A new approach to 3-hydroxyprolinol derivatives by samarium diiodide-mediated
      reductive coupling of chiral nitrone with carbonyl compounds.
AB  - A flexible diastereoselective approach to trans-(3S)-hydroxyprolinol derivatives
      is described, which is based on the samarium diiodide-mediated reductive coupling
      of the chiral 1-pyrroline N-oxide (nitrone)(S)-10 with carbonyl compounds. The
      reductive hydroxyalkylation of nitrone 10 with ketones and aromatic aldehydes is
      highly diastereoselective in establishing the C-2 chiral center of the
      pyrrolidine ring.

PMID- 19582308
TI  - Complementary chemoenzymatic routes to both enantiomers of febrifugine.
AB  - Two complementary strategies for the synthesis of febrifugine are detailed based
      on previously developed chemoenzymatic approaches to the 3-hydroxypiperidine
      skeleton. The introduction of the quinazolone-containing side chain in both
      strategies was based on an N-acyliminium ion-mediated coupling reaction.

PMID- 19582309
TI  - A concise approach to the core structures of pinnaic acid and halichlorine.
AB  - An efficient and flexible synthetic approach to the core structures of pinnaic
      acid and halichlorine is described using spirocyclic nitrone 4 as a key
      intermediate. 1,3-Dipolar cycloaddition of 4 with dipolarophile 8 provides access
      to the azaspirocyclic core of pinnaic acid 5 while the spiroquinolizidine core of
      halichlorine 6 has been synthesised via cycloaddition of 4 with dipolarophile 29.
      Nitrone 4 is accessed by oxidative ring opening of isoxazolidine 9. The utility
      of this synthetic strategy in the synthesis of C5 substituted analogues of
      pinnaic acid is also demonstrated.

PMID- 19582311
TI  - A new era for African psychiatry.

PMID- 19582312
TI  - Spirituality as an element of health science education and practice.

PMID- 19582313
TI  - HIV infection and psychiatric illness.
AB  - OBJECTIVE: To review the clinical features and current knowledge on the treatment
      of psychiatric symptoms and disorders in patients with human immunodeficiency
      virus (HIV) infection. METHOD: We searched the PubMed database combining HIV/AIDS
      with different keywords for psychiatric diagnoses and symptoms (e.g. depression,
      mania, anxiety, psychosis, dementia, substance abuse) and for
      psychopharmacological treatment. The years covered by these searches included
      1980 to 2008. RESULTS: Patients with HIV infection are at an increased risk of
      psychiatric illness. Major depressive disorder and subsyndromal depressive
      symptoms, as well as anxiety disorder and substance abuse are more prevalent
      among HIV infected individuals than among the general population. HIV-associated
      neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated
      dementia (HAD) is a serious condition during the acquired immune deficiency
      syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the
      first clinical symptom of HIV dementia. The introduction of highly active anti
      retroviral therapy (HAART) has resulted in significant decreases in morbidity and
      mortality for HIV infected patients. HAART has also decreased the incidence of
      HAD, but does not give complete protection from this condition. The utility of
      psychotropic medications in HIV patients has not been studied sufficiently as a
      basis for guidelines, and more controlled trials are needed. CONCLUSION:
      Psychiatric illness is common in HIV infected individuals, and underlines the
      importance for screening not only for cognitive impairment but also for co morbid
      mental disease in HIV-positive patients. Further studies of the neuropsychiatric
      complications during HIV disease and the use of psychotropics under these
      circumstances are clearly needed. A better understanding of the pathogenesis of
      HAD is essential to identify additional therapeutic strategies for prevention and
      treatment of this neurodegenerative disease. Studies are also needed for
      optimizing effective utilization of antiretrovirals into the CNS. Mania and
      psychosis secondary to HAD may be used as an indicator to initiate HAART,
      irrespective of CD4 count. Further research on the utility of HAART in the
      treatment of such acute neuropsychiatric symptoms associated with HIV infection
      should be initiated.

PMID- 19582314
TI  - South Africans in flux: exploring the mental health impact of migration on family
      life.
AB  - In the context of post-apartheid South Africa mental health professionals are
      increasingly faced with the complexities linked to people leaving the country,
      those left behind and those returning. In an attempt to illustrate the mental
      health challenges linked to the South African migration phenomenon, this article
      will firstly explore the global phenomenon of migration and some of the
      theoretical approaches used to understand it. The psychological impact of
      immigration on individuals and their families will also be explored. In
      conclusion the author will propose some possible preventative measures which may
      be of use to mental health professionals.

PMID- 19582315
TI  - Brain Fag Syndrome - a myth or a reality.
AB  - The Brain Fag Syndrome (BFS) is defined in the Diagnostic and Statistical Manual
      of Mental Disorders (DSM-IV) as a culture bound syndrome. BFS is a tetrad of
      somatic complaints; cognitive impairments; sleep related complaints; and other
      somatic impairments. Prince first described this psychiatric illness associated
      with study among African students in 1960. There have been questions relating to
      the nosological status of the syndrome as to whether: BFS is an objective or
      subjective phenomenon; it is one phenomenon or a variant of other known
      disorders; it is a mental illness? These three questions pose challenges to the
      culture bound/depressive or anxiety equivalent approach to the condition. The
      scope of this paper is the scope of BFS history from its first reference in the
      psychological medicine to the most contemporary descriptions in transcultural
      psychiatry. The conceptual history of BFS is divided into four major
      perspectives: Traditional medicine, Psychoanalysis, Biopsychological and
      Transcultural psychiatry. This helps to outline some of the key issues, helps to
      clarify its nosological status, its present status and helps to set the stage for
      the future progress. From its conceptual history, BFS as a phenomenon, with its
      distinct presentations, is subjectively real and is best classified with the
      framework of psychiatry, psychology and or sociology. The existence of BFS is
      evidenced by case as well as epidemiological reports of the condition in
      different locations. However, its course, response to treatment and outcome
      deserve more attention than has been given.

PMID- 19582316
TI  - Clinical characteristics and premorbid variables in childhood-onset
      schizophrenia: a descriptive study of twelve cases from a schizophrenia founder
      population.
AB  - OBJECTIVE: To analyze clinical and demographic data of childhood-onset (12 years
      and younger) schizophrenia patients collected for a genetic study in
      schizophrenia, undertaken nationally in South Africa, using multiple parameters.
      METHOD: Patients with an onset of schizophrenia at 12 years or younger, were
      included. From the Diagnostic Interview for Genetic Studies (DIGS), patients'
      information and summary report data was tabulated and analyzed. Specific
      subgroups were further compared. This sub-population of 12 subjects was further
      compared with a group of the adult sample. RESULTS: Of the 12 patients recruited,
      prominent results were: male to female ratio of 1:1; all had insidious onset of
      psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all
      patients that received ADHD treatment had ADHD treatment failure; two thirds had
      milestone delay; 58% had birth complications; a third were predominantly bottle
      fed; 42% had family history of schizophrenia; a third had family history of other
      major psychiatric conditions; all patients had at least one non-psychotic deviant
      behaviour (NPDB); no patient used cannabis; all delusions were paranoid; 92% had
      school achievement difficulty and a third had treatment resistance. Gender
      comparison included: earlier onset of psychosis in females; all females had
      aggression versus a third of males; more females had school achievement
      difficulty than males; males had more treatment resistance. Patients with MDI,
      compared to the sample average had: earlier onset of non-psychotic deviant
      behaviour; lower school drop-out rate; less social difficulty and no treatment
      resistance. CONCLUSION: The results compare well to previous research on this
      topic. The new concepts introduced by the present study require further
      investigation.

PMID- 19582317
TI  - Yoruba world view and the nature of psychotic illness.
AB  - OBJECTIVE: The Yoruba are an ethnic group in southern Nigeria. It is said that
      their world view centers around a continuous battle between forces of good and
      evil. Adverse events such as illness are due to the malevolence of enemies, using
      metaphysical means. Remedy often involves corrective metaphysical intervention,
      either exclusively or in addition to other methods, such as 'western Medicine'.
      This 'rule' is said to fit mental illness more than any other type of illness,
      although there is a lack of empirical data on the subject. This study is aimed at
      identifying elements of a Yoruba world view, and factors relevant to the
      perception and treatment of psychotic illness. METHOD: 500 Yorubas in Lagos were
      randomly sampled (with a questionnaire), and 100 'home video' films were
      analyzed. Data were analyzed for: elements of world view; elements that pertain
      to illness in general; elements that pertain to psychotic illness; how such
      illness is to be treated. RESULTS: The world view has a significant influence on
      perception of psychotic illness. CONCLUSION: It is necessary to understand a
      people's world view in order to understand (and influence) attitudes towards
      psychotic illness in themselves and other people.

PMID- 19582318
TI  - A changed climate for mental health care delivery in South Africa.
AB  - OBJECTIVE: Traditional health practice was recently mainstreamed in South Africa
      by the promulgation of the Traditional Health Practitioners Act, No. 35 of 2004.
      Due to the extent of integration of mental health in the legal definition of
      traditional health practice, promulgation of this Act also has significant
      implications for mental health care delivery. This paper explored the documented
      interface of traditional health practice with mental health care in South Africa
      over the past almost 50 years. METHOD: A preliminary overview of health
      literature was done on formal mental health care and traditional alternatives in
      South Africa since the 1950's. Important themes were identified as first step in
      a qualitative approach to identify concepts. RESULTS: The search yielded 143
      references, between 1958 and 2004, from articles, case reports, scientific
      letter, theses and chapters in books. A cross section of 56 references was
      selected for inclusion in this review of the material. CONCLUSION: The
      documentation on the interface between the two parallel systems contribute to
      establish a context against which the promulgation of the legislation to formally
      integrate and regulate African traditional health practice in South Africa can be
      considered. South African policy makers may now have ensured that a multi
      faceted, multi-cultural and multi-cosmological context for health and mental
      health care delivery has come to pass. To health administrators, though, the
      inclusion of traditional healers into the formal public health system and mental
      health may still prove to be too costly to implement.

PMID- 19582319
TI  - Sharing mental health research resources in Africa - the place of all inclusive
      consortia.

PMID- 19582320
TI  - Psychiatric disorders and general medical conditions: implications for the
      clinician.
AB  - Patients with severe mental illness have higher than expected prevalence rates of
      co-morbid general medical conditions, particularly metabolic and cardiovascular
      disease. They are also at increased risk of contracting HIV. Conversely, these
      and other medical disorders also increase the risk of developing mental
      disorders. Mental illness and general medical conditions have mutually adverse
      effects on long-term outcome. This interaction of diseases contributes
      significantly to the excess morbidity in and higher than expected standard
      mortality ratios for patients with mental illness. As medical practice becomes
      more specialized and arguably compartmentalized it may increasingly fail to
      integrate health care for patients with severe mental illness. In this paper we
      discuss the high co-morbidity of mental illness with other medical disorders as
      well some of the potential mechanisms involved. We furthermore argue that the
      bidirectional relationship between mental and medical disorders should be
      considered in the planning of treatment for either group of disorders. The
      central role of the psychiatrist in co-ordinating and integrating the health care
      of patients with severe mental illness is emphasized.

PMID- 19582322
TI  - The neuroendocrinological sequelae of stress during brain development: the impact
      of child abuse and neglect.
AB  - Severe stress during the sensitive periods of neurodevelopment, (which include
      the prenatal period, infancy, childhood and adolescence), has a long-lasting
      organizing effect on the brain and stress axes. Child abuse and neglect thus
      exert a cumulative harmful effect on neuroendocrinological development, which
      persists into adulthood. It is not merely the memory of the trauma which leaves a
      mark, but rather the effect on neurodevelopment which negatively influences the
      ability of adult survivors of childhood maltreatment to cope with current
      stressors. The victims of child abuse and neglect are likely to maltreat their
      own children and so perpetuate the intergenerational transmission of child
      maltreatment. In this paper relevant normal brain development is first
      summarized. Child abuse/neglect is next discussed with detailed reference to the
      aberrant neuroendocrinological development that is known to occur. We
      specifically examine effects on the hypothalamo-pituitary-adrenal and central
      noradrenergic-sympathoadrenomedullary stress axes and other neurotransmitter
      systems before turning to changes described in the cerebral volumes, corpus
      callosum and cortical hemispheres, prefrontal cortex and amygdalae, superior
      temporal gyrus, hippocampus as well as the cerebellar vermis.

PMID- 19582321
TI  - Mental health literacy: focus on developing countries.
AB  - Mental health literacy refers to knowledge and beliefs about mental disorders
      which aid their recognition, management and prevention. This is a non-systematic
      review of published articles on mental health literacy in the general population
      and among primary healthcare workers, in particular, in developing countries,
      sourced from Medline, PsychInfo and African Healthline databases (1990-2006). Our
      review of the literature suggests that public knowledge about mental disorders as
      medical conditions, and their evidence based treatment strategies, in developing
      countries may be generally poorly or inaccurately understood. The review also
      reveals that improving the mental health literacy among primary health care
      professionals is imperative. Poor mental health literacy can be an obstacle to
      providing treatment for those in need, and is of particular concern in low and
      middle-income countries where mental health services are already scarce. It is
      likely that strategies for improvement will need to be comprehensive and
      innovative, taking advantage of opportunities and meeting challenges faced in the
      developing world.

PMID- 19582323
TI  - Depression among Sesotho speakers in Mangaung, South Africa.
AB  - OBJECTIVE: Depression will be the most common mental disorder by 2020, and it is
      also expected to be the second leading cause of disability, after cardiac
      diseases. Moreover, depression is likely to be a major public health burden in
      the future. This study evaluates the influences of culture on the symptoms of
      depression among Sesotho speakers. METHOD: An evaluation of a sample of 100
      participants diagnosed with depression was conducted, using the Psychiatric
      Interview Questionnaire. RESULTS: It was found that depression among Sesotho
      speakers is manifested in three areas: somatic symptoms, perceptual disturbances
      and disturbances of the thought processes. CONCLUSION: Since it has become clear,
      on the basis of the investigation, that depression is a culturally diverse
      phenomenon, the authors also recommend that research in this regard should be
      conducted from a multidisciplinary perspective, so that other paradigms,
      including those of sociology and anthropology, can also be included.

PMID- 19582324
TI  - Level of maternal education and performance of Black, South African infants on
      the 1996 Griffiths Mental Development Scales.
AB  - OBJECTIVE: The study compared the performance on the Griffiths Mental Development
      Scales of Black, South African infants with mothers who had twelve or more years
      of education and who were professionally employed with infants of mothers with
      fewer than twelve years of education and who were employed in non-professional
      jobs. METHOD: The sample consisted of 40 infants (aged 13-16 months), to whom the
      Griffiths Mental Development Scales was administered. RESULTS: The infants with
      professional mothers performed significantly better than their counterparts with
      non-professional mothers on the General Quotient, as well as on the Locomotor
      Scale. While maternal level of education did not appear to distinguish between
      infants in terms of social, fine motor, language, hearing, processing speed or
      practical reasoning, it did discriminate in terms of gross-motor functioning.
      CONCLUSION: It is suggested that, as the infant develops, the skills assessed by
      the Griffiths Scales, which are initially differentiated, become increasingly
      interrelated. Consequently, poor gross-motor skills, which may be more likely in
      infants from a low socio-economic status, may have far-reaching implications.
      Thus, it is important to consider maternal level of education and the socio
      economic status background of the infant, as this may influence overall
      performance on the Scales.

PMID- 19582325
TI  - Post traumatic stress disorder symptoms in a psychiatric population not
      presenting with Trauma: a preliminary study.
AB  - OBJECTIVE: Post Traumatic Stress Disorder (PTSD) is a diagnostic category used to
      describe symptoms arising from emotionally traumatic experience(s). Research
      suggests that PTSD may be under- diagnosed when trauma is not the presenting
      problem or when not the focus of clinical intervention. There is a dearth of
      South African information on the prevalence of PTSD in a psychiatric population.
      The aim of this study was to determine the prevalence and comorbidity of PTSD in
      a psychiatric population, not presenting on the basis of trauma. METHOD: The
      study was cross sectional and conducted at a psychiatric outpatient clinic in the
      Durban Metropolitan area. The sample was obtained from patients seen at follow up
      over a period of twelve weeks. The researcher randomly selected prospective
      participants and at the end of their consultation the purpose of the study was
      explained and they were invited to participate. Demographic characteristics and
      diagnosis were recorded. Thereafter, the Zulu version of the Modified
      Posttraumatic Diagnostic Scale (MPDS) was administered and data collected.
      RESULTS: The study demonstrated that 22% of subjects reported symptoms of PTSD
      where the primary presentation was not trauma related. CONCLUSION: A significant
      number of psychiatric patients presenting for non-trauma related psychopathology
      report symptoms of PTSD when specifically questioned. The findings suggest that
      such questioning may be overlooked when dealing with psychiatric patients who do
      not specifically present on the basis of trauma.

PMID- 19582326
TI  - Impact of tertiary and quaternary service funding processes on medication
      selection in the SA essential drugs programme.

PMID- 19582327
TI  - Involuntary treatment of psychiatric patients in South Africa.
AB  - Society deems that mentally ill patients who lack insight and judgement may be
      treated involuntarily in institutions as a way of protecting them and the society
      around them. The ethical principle of 'paternalism' supersedes the principle of
      'autonomy'. In South Africa, the new Mental Health Care Act (MHCA), No 17, 2002
      has raised the issues and profile of mental health and serves as an advocate for
      mental health care users. In accordance with this MHCA, a mental health care user
      may be treated involuntarily at a health establishment on an inpatient basis
      under very specific regulations that serve to protect the users' rights as much
      as possible. However, the implementation of involuntary treatment whilst
      upholding users' rights within a health care service, which is plagued by human
      resource and infrastructure constraints, is extremely difficult and likely to
      infringe on these rights. The understanding of the regulations and principles
      governing involuntary treatment is important as it is a means of helping users'
      who despite needing it, refuse such treatment. If it is done sensitively,
      respectfully and conservatively, we can both protect the users' and societies'
      interests whilst at the same time are compliant with the principles of the MHCA.

PMID- 19582328
TI  - Management of perceived mental health problems by spiritual healers: a Nigerian
      study.
AB  - OBJECTIVE: Anecdotal reports and research findings have suggested that religious
      healers are widely consulted by many Nigerians in time of mental health
      crisis.The study aimed at examining the knowledge, attitude and practice of
      mental health care among a syncretic Church's healers, and their readiness to
      cooperate with Psychiatrists. METHOD: A modified, pilot-tested, selfcompleted
      questionnaire was used to obtain information from consenting spiritual healers
      who satisfy the inclusion criteria. Focus group discussions (FGDs), Participatory
      Observation (PO) and Key Informant Interviews (KII) were used to corroborate or
      refute the findings. RESULTS: The respondents' knowledge of mental disorders was
      limited to psychotic disorders; their explanatory model was similar to beliefs of
      the populace. In practice, they combined some modern medical approach, some
      native methodology and some eclectic religious practices such as prophecy, trance
      and dream. Only 6% of them ever referred their clients to medical practitioners.
      CONCLUSION: Religious healers still constitute an important route to access
      mental health care providers to some Nigerians.

PMID- 19582329
TI  - Post traumatic stress disorder: undiagnosed cases in a tertiary inpatient
      setting.
AB  - OBJECTIVE: Post traumatic stress disorder (PTSD) is a common, debilitating
      anxiety disorder characterized by emotional and physical symptoms that may occur
      after exposure to a severely traumatic event. Since it occurs commonly as a
      comorbid diagnosis with other mood- and anxiety disorders, we postulated that
      this disorder may be under- diagnosed in therapeutic wards where anxiety and mood
      disorders are treated. The study thus sought to determine the prevalence of
      undiagnosed PTSD in an inpatient population, and to compare the demographic
      details and comorbid diagnoses of subjects with and without PTSD. METHOD: The
      Clinician-administered PTSD Scale for DSM-IV (CAPS) was administered to 40
      subjects who were inpatients in a therapeutic ward of a large psychiatric
      hospital and who had never had a diagnosis of PTSD before. RESULTS: 16 (40%)
      subjects met the DSM-IV criteria for PTSD. We did not find significant clinical
      differentiating factors between subjects with and without PTSD; however subjects
      with PTSD were more likely to use cannabis. CONCLUSIONS: PTSD remains undiagnosed
      in many patients admitted to therapeutic units.

PMID- 19582330
TI  - Clinical neuropsychiatric correlates and EEG findings among children with
      developmental disorders in Lagos, Nigeria.
AB  - OBJECTIVE: Developmental disorders with or without associated neuropsychiatric
      complications continue to be one of the major health problems in Africa. The
      grossly inadequate management/ rehabilitative facilities further worsen this. A
      prospective study aimed at finding the types of developmental disorders and
      associated neuropsychiatric complications among children aged </=15 years that
      presented with developmental disorder in the study centers over 36 month study
      duration. METHODS: The study was carried out in the paediatric and child
      psychiatric clinics as well as the Electroencephalographic (EEG) unit of two
      major health facilities in Lagos, Nigeria: Lagos University Teaching Hospital
      (LUTH) and Psychiatric Hospital, Yaba, Lagos. For each subject, socio-demographic
      data was obtained and appropriate clinical evaluation was carried out to obtain
      the necessary data and clinical diagnoses. Furthermore, each of the subjects had
      waking EEG recording using 20-channel computerized Medelec(R)EEG machine. The EEG
      interpretation was blinded to the clinical history of the subjects. RESULTS:
      Overall, one hundred and eleven (111) subjects were evaluated over the 36 month
      study period. The cohort was made up of 63 (56.8%) males and 48 (43.2%) females.
      The mean age was 4.8 (+/-3.9) years, with most subjects falling in the age group
      of 0-5 years(69.4%). Mixed specific developmental disorders were most common
      (55%) followed by that of specific developmental disorders of speech and language
      (34.2%). Forty-one (36.9%) subjects suffered from one or more types of
      complications, with seizure, 22(19.8%) being the most common. The waking EEG
      recording was normal in 22 (19.8%) subjects; while abnormal epileptiform
      activities were found in 85 (76.6%) of recordings. No statistically significant
      relationship existed between EEG abnormalities and the factors of age and
      clinical diagnoses (i.e developmental abnormalities). CONCLUSION: The small
      number of subjects in this study is a major hindrance to drawing a general
      conclusion. However, it has been shown that a number of the cohort in addition to
      their developmental disorders suffered from such complications as seizures,
      hyperactivity etc. Furthermore, a significant proportion had EEG abnormalities of
      the epileptiform types possibly reinforcing the previously known fact of
      prevalent subtle brain damage among African children. The need for preventive
      health care is therefore emphasized.

PMID- 19582331
TI  - Long stay patients in a psychiatric hospital in Lagos, Nigeria.
AB  - OBJECTIVE: In the face of recently introduced government health reform and the
      dwindling number of available beds for acutely ill patients, a cross sectional
      study was carried out on long-stay patients at the 100 years old psychiatric
      hospital Yaba, Lagos, Nigeria with a view to discharging most of them. METHOD:
      Necessary consent was obtained from the Hospital Research and Ethical Committee.
      All the long-stay patients were evaluated with a specially designed proforma to
      elicit socio-demographic, clinical and long-stay variables. Further more, each of
      them had clinical assessment to make diagnosis in accordance with ICD - 10 and
      finally, the subjects were also assessed with the Brief Psychiatric Rating Scale
      (BPRS). RESULTS: Fifty-one (51) subjects; that is, occupying 10.7% of the
      hospital functional beds fulfilled the criteria of long-stay. They included 36
      (70.6%) males and 15(24.4%) females. The mean age was 47.3 inverted exclamation
      markA16.5 years with age range of 18-92 years. The average length of stay was
      11.4 inverted exclamation markA15.0 years and range of 0.5 to 57 years; with
      significant gender difference (males higher than females) (t =3.51, p<0.02). The
      vast majority of the subjects were diagnosed with schizophrenia (84.3%), followed
      by mental retardation with seizure disorder (5.9%). One-third (33.3%) of the
      subjects had co-morbid physical pathologies most especially epilepsies,
      hypertension, Koch inverted exclamation mark s disease, HIV/AIDS. Despite being
      on high doses of antipsychotics (conventional and/or atypical) the majority of
      the subjects (86.3%) exhibited poor mental state with BPRS scores of inverted
      exclamation markY10. The mean BPRS score was 23.6 inverted exclamation markA22.0
      and range of 4-56 with a significant gender difference (t = 3.66, p< 0.02).
      CONCLUSION: These patients would continue to require long-stay hospitalization
      despite been a burden to the study center; or, in the alternative provision of
      mid Cway facilities for their rehabilitation.

PMID- 19582332
TI  - Depression in African women presenting for psychological services at a general
      hospital.
AB  - OBJECTIVE: Despite the increase in knowledge of depression, little is known about
      depression among African populations, especially African woman. In South Africa,
      inadequate mental health services generally and specifically for African people
      in our society, has led to under reporting and under diagnosing of the disorder.
      The object of the study was to understand depression in African women attending a
      state health service. METHOD: Clinical records of all patients presenting with
      depression to a general hospital located in a densely populated African township,
      over a 2 year period, were examined. RESULTS: The epidemiological data is
      described. Depression in these women was related to poverty, overcrowding,
      unemployment, high levels of crime, lack of services and sexual abuse.
      CONCLUSION: African women return to a social context within which depression is
      increasingly prevalent. Establishing psychological services relevant to needs as
      well as means of ensuring that therapeutic gains extend to their social context
      are considered.

PMID- 19582333
TI  - The impact of CPOE medication systems' design aspects on usability, workflow and
      medication orders: a systematic review.
AB  - OBJECTIVES: To examine the impact of design aspects of computerized physician
      order entry (CPOE) systems for medication ordering on usability, physicians'
      workflow and on medication orders. METHODS: We systematically searched PubMed,
      EMBASE and Ovid MEDLINE for articles published from 1986 to 2007. We also
      evaluated reference lists of reviews and relevant articles captured by our search
      strategy, and the web-based inventory of evaluation studies in medical
      informatics 1982-2005. Data about design aspects were extracted from the relevant
      articles. Identified design aspects were categorized in groups derived from
      principles for computer screen and dialogue design and user guidance from the
      International Standard Organization, and if CPOE-specific, from the collected
      data. RESULTS: A total of 19 papers met our inclusion criteria. Sixteen studies
      used qualitative evaluation methods and the rest both qualitative and
      quantitative. In total 42 CPOE design aspects were identified and categorized in
      seven groups: 1) documentation and data entry components, 2) alerting, 3) visual
      clues and icons, 4) drop-down lists and menus, 5) safeguards, 6) screen displays,
      and 7) auxiliary functions. CONCLUSIONS: Beside the range of functionalities
      provided by a CPOE system, their subtle design is important to increase
      physicians' adoption and to reduce medication errors. This requires continuous
      evaluations to investigate whether interfaces of CPOE systems follow normal flow
      of actions in the ordering process and if they are cognitively easy to understand
      and use for physicians. This paper provides general recommendations for CPOE
      (re)design based on the characteristics of CPOE design aspects found.

PMID- 19582334
TI  - Integrated segmentation and non-linear registration for organ segmentation and
      motion field estimation in 4D CT data.
AB  - OBJECTIVES: The development of spatiotemporal tomographic imaging techniques
      allows the application of novel techniques for diagnosis and therapy in the
      medical routine. However, in consequence to the increasing amount of image data
      automatic methods for segmentation and motion estimation are required. In
      adaptive radiation therapy, registration techniques are used for the estimation
      of respiration-induced motion of pre-segmented organs. In this paper, a
      variational approach for the simultaneous computation of segmentations and a
      dense non-linear registration of the 3D images of the sequence is presented.
      METHODS: In the presented approach, a variational region-based level set
      segmentation of the structures of interest is combined with a diffusive
      registration of the spatial images of the sequence. We integrate both parts by
      defining a new energy term, which allows us to incorporate mutual prior
      information in order to improve the segmentation as well as the registration
      quality. RESULTS: The presented approach was utilized for the segmentation of the
      liver and the simultaneous estimation of its respiration-induced motion based on
      four-dimensional thoracic CT images. For the considered patients, we were able to
      improve the results of the segmentation and the motion estimation, compared to
      the conventional uncoupled methods. CONCLUSIONS: Applied in the field of
      radiation therapy of thoracic tumors, the presented integrated approach turns out
      to be useful for simultaneous segmentation and registration by improving the
      results compared to the application of the methods independently.

PMID- 19582335
TI  - The training of otorhinolaryngologists in Brazil.

PMID- 19582336
TI  - Clinical data and hearing of individuals with Alport syndrome.
AB  - Alport Syndrome (AS) is a hereditary disease, characterized by nephropathy, often
      times with sensorineural hearing loss and ocular defects. AIM: to analyze the
      clinical and hearing information from individuals with AS, more specifically the
      correlation between renal disorder and hearing loss (HL). STUDY DESIGN: clinical
      prospective with cross-sectional cohort. MATERIALS AND METHODS: 37 individuals
      underwent otorhinolaryngological evaluation and were submitted to audiologic
      tests. For HL statistical analysis we considered only the results from the pure
      tone audiometries. RESULTS: of the 28 individuals with clinical alterations, we
      found 46.4% of DLX and 53.6% of AD. HL happened to 46.1% of the individuals
      evaluated. 12 patients presented HL in the audiometric test: 11.5% mild and 34.6%
      moderate. Comparing the normal relatives with those with renal disorder; all that
      had HL also had renal disorder. In 30.8% the curve shape was mild descending in
      the high frequencies and in 11.5% it was flat. CONCLUSIONS: The inheritance
      pattern distribution does not match literature descriptions. HL is a frequent
      extra-renal finding. There is an association between renal involvement and HL (p=
      0.009). The most frequent curve shapes: mild descending in the high frequencies
      and flat. There was no association between HL and age. There is no correlation
      between the HL and gender in this group.

PMID- 19582337
TI  - Vestibular function in children underperforming at school.
AB  - Learning is a complex, dynamic process, structured from motor and perception
      skills which, when cortically processed, give birth to cognition. Balance is a
      fundamental neurological function that helps us maintain proper postures, an
      essential factor in learning and a sign or neurologic maturity. AIM: this paper
      aims to study vestibular function in children underperforming at school. STUDY
      DESIGN: this is a cross-sectional study. MATERIALS AND METHOD: eighty-eight
      children with ages ranging between 7 and 12 years attending the public schools of
      Piracicaba from 2004 to 2006 were enrolled. All children were interviewed,
      submitted to ENT examination, hearing tests, and vestibular examination. RESULTS:
      fifty-one percent of the participants had no reported difficulties at school,
      whereas 49.0% were underperforming at school. Under vestibular examination, 73.3%
      of the children performing well at school had normal findings, whereas 32.6% of
      the underperforming children had normal test results. Unilateral and bilateral
      irritative peripheral vestibular alterations were found in 67.4% of the
      underperformers and in 26.7% of the children not experiencing difficulties at
      school. CONCLUSION: all vestibular alterations found had an irritative peripheral
      origin. There was a statistically significant association between vestibular
      alteration and poor performance at school.

PMID- 19582338
TI  - Results of stapes surgery for otosclerosis with two kinds of prosthesis in
      residency training.
AB  - Stapes surgery is one of the approaches indicated to treat conductive hearing
      loss secondary to otosclerosis. The procedures requires skill and experience from
      the surgeon and is part of medical residency training. AIMS: To assess which type
      of prosthesis (Teflon or metal/steel) presents the best results in surgeries
      performed by residents and the incidence of complications. MATERIALS AND METHODS:
      we retrospectively assessed 189 interventions that counted on the active
      participation of resident physicians, and we compared the two types of prosthesis
      used. Audiometric results were analyzed following the guidelines from the
      Committee on Hearing and Equilibrium and also according to the Amsterdam Hearing
      Evaluation Plots. RESULTS: Bone-air gap reduced in an average value of 21.90 dB
      (p<0.05) after the surgery in the group that received the Teflon prosthesis and
      21.37 dB (p<0.05) in the group that received the mixed prosthesis, and gain in
      SRI was of 22.33 and 26.10 dB (p<0.05), and the air-bone gap was below 20 dB in
      80.6% and 85.04%, respectively. CONCLUSIONS: We did not see differences in the
      audiometry and in the incidence of complications when we compared the type of
      prosthesis used. We believe it is valid to continue teaching this procedure in
      medical residency training programs, regardless of the type of prosthesis.

PMID- 19582339
TI  - Analysis of histopathological aspects in acquired middle ear cholesteatoma.
AB  - Middle ear cholesteatomas are characterized by the presence of stratified
      squamous epithelium in this cavity with highly invasive properties causing bone
      destruction and it may lead to complications. AIM: To study the histopathological
      features in acquired cholesteatomas of the middle ear, correlating this data with
      patient age. STUDY DESIGN: clinical and experimental cross-sectional study.
      MATERIAL AND METHODS: Samples were obtained from 50 patients submitted to
      otologic surgery for the removal of middle ear cholesteatomas from 2006 to 2007.
      Thirty four patients were adults and 16 were children. Samples were studied by
      histological analysis. RESULTS: We found the presence of epithelial atrophy
      (78%), epithelial acanthosis (88%), hyperplasia of the basal layer (88%) and
      formation of epithelial cones (62%). There was a positive and significant
      correlation between histopathological variables (such as epithelial acanthosis,
      hyperplasia of the basal layer and formation of epithelial cones).
      Histopathological variables presented no statistical significant difference in
      both age groups (p>0,05). CONCLUSION: Cholesteatomas have hyperproliferating
      characteristics with epithelial acanthosis, hyperplasia of the basal layer and
      the presence of epithelial cones in the matrix.

PMID- 19582340
TI  - Ototoxicity and otoprotection in the inner ear of guinea pigs using gentamicin
      and amikacin: ultrastructural and functional aspects.
AB  - Ototoxicity is still a challenge to medicine. The discovery of self-protecting
      endogenous mechanisms of the outer hair cells associated with their functional
      and ultra-structural assessment methods has opened new horizons in the
      understanding and controlling of these mechanisms. AIM: this paper aimed at
      establishing whether or not underdoses of gentamicin could protect the inner ear
      against the harmful effects of amikacin, based on these protection mechanisms and
      determine if the otoacoustic emission amplitudes could be associated with the
      level of hair cell integrity. MATERIALS AND METHODS: Experimental study. We used
      31 guinea pigs. They were injected with saline solution, gentamicin and amikacin,
      alone and in combinations -intramuscular injections - during 12, 30 and 42 days.
      The otoacoustic emissions were recorded in the beginning and at the end of the
      experiment, comparing it with the cochlear integrity study carried out by
      electron microscopy. RESULTS: gentamicin underdoses did not protect the inner ear
      against amikacin toxicity; the reduction in otoacoustic emissions was strongly
      associated with an increase in hair cell lesions. CONCLUSION: these findings help
      understand inner ear otoprotection and ototoxicity. Establishing the correlation
      between the emissions amplitude an cell integrity plays an important role in the
      follow up of hair cell damage, with possible monitoring of ototoxicity caused by
      drugs in humans.

PMID- 19582341
TI  - Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in
      squamous cell carcinomas of the larynx.
AB  - Prognostic histological factors may contribute to determine the evolution of this
      neoplasia. AIM: To correlate p53 and Ki-67 immunohistochemical expression with
      age, histological degree, lymph node involvement and pathological staging in
      patients with laryngeal epidermoid carcinomas. METHODS: We assessed thirty
      consecutive cases of laryngeal epidermoid carcinomas submitted to
      immunohistochemistry to check the expression of p53 e Ki-67 antibodies. RESULTS:
      Mean age was of 56.2 years and the immunoexpression of the markers was observed
      in the group with more than 50 years of age, especially that o the ki-67 antibody
      (p=0.032). There was no relation between p53 and Ki-67 with lymph node
      involvement. Ki-67 was expressed in 70% of the high histology level cases and in
      80% in the low histology ones; while p53 was of 70% only in the high level cases.
      Pathology staging showed that in the group of advanced carcinomas, p53 expression
      was of 61.5%, while Ki-67 proved positive for the early cases (100%) and advanced
      (73.1%). CONCLUSION: There were no significant differences between p53 and Ki-67
      immunoexpression in laryngeal epidermoid carcinoma, except in the group of
      patients with more than 50 years of age, when Ki-67 expression was significantly
      higher.

PMID- 19582343
TI  - Comparison between telelaryngoscopy and suspension laryngoscopy in the diagnosis
      of benign vocal fold lesions.
AB  - Proper diagnosis of laryngeal benign lesions still brings doubts among
      experienced laryngologists, despite current diagnostic progress. AIM: The goal of
      this study was to compare telelaryngoscopy (preoperative) with suspension
      laryngoscopy (intraoperative) on the diagnosis of vocal fold benign lesions.
      MATERIALS AND METHODS: We carried out a restrospective study analyzing 79 charts
      from patients followed up in a University Hospital. In all the charts there was
      at least diagnostic hypothesis suggested by telelaryngoscopy, which was later on
      compared to intraoperative findings of suspension laryngoscopy. RESULTS: Almost
      two-thirds of the patients were females, with ages varying between 12 and 66
      years (mean of 37 years). Of the 79 patients studied, we diagnosed 95 lesions
      with telelaryngoscopy and 124 with suspension laryngoscopy. The most frequently
      found benign lesion was the vocal polyp in both methods. In 64.5% of the cases
      the diagnosis of the lesions in the outpatient ward was the same as those in the
      surgical findings. CONCLUSION: Laryngologists must be prepared to alter their
      surgical planning and treatment approaches because of diagnostic changes that may
      happen during surgery.

PMID- 19582342
TI  - Prognostic factors in squamous cell carcinoma of the oral cavity.
AB  - Researchers have been looking for factors that can influence the prognosis of
      oral cancer, because its outcome is highly uncertain. AIM: To evaluate variables
      that can impact the survival rate of patients with squamous-cell carcinoma of the
      oral cavity. MATERIAL AND METHODS: Data analysis of 45 patients from January,
      2001 to January, 2006. Survival rate curves have been estimated using the Kaplan
      Meier method and they have been compared through the log-rank test and the Cox
      regression standard. STUDY DESIGN: Retrospective analysis. RESULTS: Total five
      year survival rate was of 39% fpr these patients. Only the neck metastases
      (p=0.017), postoperative radiotherapy (p=0.056) and diseased margin(p=0.004)
      variables had statistic relevance. Survival rate was lower in patients with neck
      metastases, margins involved and those who underwent postoperative radiotherapy,
      in other words, those with the most aggressive tumors. After adjustment,
      radiotherapy did not prove to be statistically relevant. It is likely that the
      survival rate of 39% was due to the high number of patients with metastasis (52%)
      and because the samples were mostly of tongue and mouth floor diseases (82%),
      which are the hardest to control. CONCLUSION: Neck metastases and diseased
      margins of oral cavity carcinomas are the prognostic factors that can most impact
      the survival rate.

PMID- 19582344
TI  - Association between hearing loss level and degree of discomfort introduced by
      tinnitus in workers exposed to noise.
AB  - Hearing loss and tinnitus impact the lives of workers in every instance of their
      lives. AIM: This paper aims to investigate the existence of a dose-response
      relationship between hearing loss and tinnitus by determining whether higher
      levels of hearing loss can be associated with increased tinnitus-related
      discomfort. MATERIALS AND METHOD: This cross-sectional case study assessed 284
      workers exposed to occupational noise through pure tone audiometry. Test results
      were categorized as defined by Merluzzi. Individuals complaining of tinnitus
      answered the adapted and validated Brazilian Portuguese version of the Tinnitus
      Handicap Inventory. A generalized linear model was adjusted for binomial data to
      test the interaction between these factors. RESULTS: Over 60% of the ears
      analyzed had hearing loss, while more than 46% of them had tinnitus. Tinnitus
      prevalence and risk rates increased as pure tone audiometry results got worse.
      The association between both, considering all hearing loss degrees, was
      statistically significant. CONCLUSION: The results point to a statistical
      association between hearing loss and tinnitus; the greater the hearing loss, the
      greater the discomfort introduced by tinnitus.

PMID- 19582345
TI  - Temporal organization skills in cochlear implants recipients.
AB  - Processing acoustic clues from the sounds of speech depends on the proper
      perception of the frequency and duration of stimuli as a sequence of events. AIM:
      To assess the capacity for temporal organization in users of multichannel CI.
      METHOD: 14 normal hearing individuals formed the control group, matching in age
      and gender other 14 users of multichannel CI, who made up the study group, and
      they were assessed and compared as to the Frequency Patterns Test (FPT) and
      Duration Patterns Test (DPT). RESULTS: CI users had good performance in temporal
      organization tasks, with mean results of 48.7% in the FPT and 59.6% in the DPT.
      For the control group, mean performance at the FPT was of 63.4% and in the DPT of
      64.6%. We did not see statistically significant difference between the results
      from the control and study groups. CONCLUSION: The CI provided favorable
      performance in the tasks that required temporal organization skill for
      individuals evaluated in this study.

PMID- 19582346
TI  - Plug cartilage tympanoplasty in children.
AB  - The treatment of tympanic membrane perforations in the pediatric population with
      sequelae of chronic otitis media represents a challenge to otolaryngologists.
      AIM: To assess the clinical and audiometric results of the inlay technique with a
      tragus cartilage plug. MATERIALS AND METHODS: We assessed 23 patients (ages
      between 1 and 15 years) who underwent plug tympanoplasty. STUDY DESIGN: clinical
      retrospective. RESULTS: Repair success rate was of 82.6%, with audiometric
      parameters improvement in 87.5% of the patients. Complications were minimum.
      CONCLUSION: Considering the results attained, this method of tympanoplasty should
      be considered a good treatment option for tympanic membrane perforation in
      children.

PMID- 19582347
TI  - Auditory processing assessment in older people with no report of hearing
      disability.
AB  - In the elderly, the results of central auditory pathways behavioral assessments
      are considered to be difficult to read because of the possible interference of
      peripheral auditory pathway involvement. AIM: Assess the efficacy of the central
      auditory function in elderly patients who do not complain of hearing. MATERIALS
      AND METHODS: Case study involving 40 individuals within the age range of 60 to 75
      years. The patients underwent auditory processing evaluation based on anamnesis,
      otorhinolaryngological exam, threshold tonal audiometry, speech recognition
      threshold, speech recognition index, immittance measures, stapes reflex study,
      synthetic phrases identification test with ipsilateral competitive message,
      frequency pattern test and alternate twin-syllable test through dichotic task;
      age range and hearing loss influenced results from the phrases identification
      with ipsilateral competitive message. Percentages of right answers below normal
      standards were seen in the three tests that assessed the central auditory
      functions. CONCLUSION: Elderly individuals who did not complain of hearing
      presented relevant prevalence of signs of central auditory function
      inefficiencies.

PMID- 19582348
TI  - Selected bacterial recovery in Trinidadian children with chronic tonsillar
      disease.
AB  - Pharyngotonsillitis in children is widely treated with antibiotics. AIM: To
      examine tonsil surface and core microflora following elective adenotonsillectomy
      in children. METHODS: Tonsils of 102 Trinidadian children were prospectively
      examined for surface and core bacteriological culture and identification between
      2005-2006. RESULTS: Tonsils (360) yielded 800 isolates of Streptococcus spp.
      (51.3%), Staphylococcus spp. (42.3%) and Gram-negative genera (6.4%). Surface and
      core recovery of staphylococci and streptococci were similar (p>0.05). More
      (p<0.001) surfaces (82.2%) than cores (63.3%) grew Streptococcus spp.; alpha
      haemolytic Streptococcus prevalence was higher (p<0.001) than ss-haemolytic
      Streptococcus on surfaces (74.4% vs. 18.6%) than cores (58.9% vs. 13.7%).
      Surfaces and cores were not concordant for streptococci (p<0.0004) and alpha
      haemolytic Streptococcus (p<0.007). Surface and core ss-haemolytic Streptococcus
      yield was higher (p<0.05) in 6-16 than 1-5 year olds (31% and 23.8% vs 12.5% and
      8%). S. pyogenes surface and core prevalence was (84.6% vs 70%) and (50.0% vs
      25.0%) in older and younger children respectively. Klebsiella spp. (6.6 %, 2.2%),
      Proteus (4.4%, 4.4%) and Pseudomonas (4.4 %, 1.1%) grew on surfaces and cores
      respectively. CONCLUSION: Tonsil surfaces yield higher surface than core carriage
      for streptococci overall and for alpha haemolytic streptococci. Older children
      grow more beta-haemolytic streptococci and are high colonizers of S. pyogenes.
      Studies probing the mechanisms of streptococcal adhesions in Trinidadian children
      are suggested.

PMID- 19582349
TI  - Ototoxicity study in workers exposed to organophosphate.
AB  - Occupational and environmental exposure to agricultural pesticides represent an
      important health care problem in our country. Among the symptoms presented,
      dizziness stands out, because of a probable toxic action. AIM: The goal of our
      study was to characterize vestibular test results from rural workers
      occupationally and environmentally exposed to organophosphates used in
      agricultural pesticides. MATERIALS AND METHODS: We carried out a cohort cross
      sectional study with 18 rural workers from Teresopolis, RJ. Age ranged between 16
      and 59 years, with a mean value of 39.6 years, 5 were males and 13 females. We
      used three questionnaires with questions associated with general and auditory
      health, and more specific questions about dizziness and its association with
      work. All workers underwent clinical evaluation, audiometry and
      vectoelectronystagmography. RESULTS: Results showed that 16 workers had
      irritative peripheral body balance disorder and 7 workers had sensorineural
      hearing loss, thus suggesting that agricultural pesticides cause vestibular
      alterations through a slow and silent intoxication. CONCLUSIONS: Medical care for
      this population exposed to neurotoxic substances require an interdisciplinary
      approach, to guarantee efficient preventive and therapeutic measures.

PMID- 19582350
TI  - Formal auditory training in elderly hearing aid users.
AB  - It is of paramount importance to install hearing rehabilitation programs for the
      elderly. AIM: To check the efficacy of a forma auditory training program for
      elderly patients fitted with hearing aids for at least three months, by means of
      speech recognition tests and self-assessment questionnaires. METHODS:
      Longitudinal contemporary cohort study. We selected 13 elderly hearing aid users,
      using intra-canal hearing aids in both ears, from both genders, with average age
      of 65.3 years. This group was randomly divided in Experiment Group and Control
      Group. The Experiment Group underwent seven formal auditory training sessions,
      aiming at stimulating their hearing skills for hearing closing, memory,
      attention, background figure and binaural integration. The participants were
      assessed by three behavioral tests and one self assessment questionnaire.
      RESULTS: The elderly from the Experiment Group had significantly better
      performance in the assessments after auditory training in comparison to the
      Control Group. CONCLUSION: The formal auditory training program in a soundproof
      booth, associated with the use of hearing aids, improves speech recognition
      performance and reduces the perception of auditory handicap for the elderly who
      use intra-canal hearing aids.

PMID- 19582351
TI  - Steroid injection in chronic inflammatory vocal fold disorders, literature
      review.
AB  - Steroids are potent inhibitors of inflammation and wound repair. Local
      administration of steroids directly into the larynx has been reported in many
      laryngeal diseases. AIM: The purpose of this study is to review related
      literature about the use of steroid injection in patients with benign,
      inflammatory and chronic vocal disease. METHODOLOGY: We performed an electronic
      survey in Medline database and selected clinical trials regarding steroid use in
      benign laryngeal diseases. RESULTS: Steroids are indicated in these situations:
      1) acute inflammatory diseases, mainly when edema compromises the airways; 2)
      auto- immune disease with laryngeal involvement; 3) laryngeal stenosis; 4) benign
      lesions of the vocal folds, e.g., nodules, polyps and Reinke's edema, to reduce
      the inflammatory reactions before phonosurgery or in an attempt to avoid surgery;
      5) In phonosurgery, aiming to reduce scarring. In this case, it could be used as
      a preventive measure in vocal fold scarring, or for scar treatment. CONCLUSION:
      Steroids may be considered an important therapeutic option in the management of
      many diseases, specially the inflammatory ones, associated with vocal changes.

PMID- 19582352
TI  - Post-piercing perichondritis.
AB  - Piercing has become more and more popular among adolescents. The procedure is
      generally performed by unqualified professionals and carries its risk. Non
      sterilized material or inappropiate hygiene increases the possibility of
      perichondritis and celulitis. The disease is characterized by erythema of the
      auricula pinna, unbearable pain and fever. Left untreated, the condition
      progresses with edema along the auricula and abscess formation that may result in
      ischemic necrosis and a cauliflower anesthetic deformation. The most common
      bacteria is Pseudomonas aeruginosa. In cases with abscesses, drainage is
      necessary along with antibiotic therapy guided by cultures and antibiogram. AIM:
      The aim of this case report was to review the past 10 years of published papers
      dealing with anatomical aspects of the auricular pinna, the history of piercing
      and its most common complications. METHODS: A case report of perichondritis after
      'high' ear piercing that required surgical treatment and that progressed with no
      esthetic loss. RESULTS: Theoretical and practical experience based on a review
      and a report of a case that progressed satisfactorily. CONCLUSIONS: The increased
      incidence of perichondritis in adolescents should require more elaborated primary
      prevention measures.

PMID- 19582353
TI  - Oropharyngeal dysphagia in dermatomyosites: case report and literature review.
AB  - We present a rare case of dermatomyosites associated with severe oropharyngeal
      dysphagia. A 13 year old female patient, being followed at the Rheumatologic
      Department, was referred to the Otolaryngology Department of the University of
      Sao Paulo School of Medicine Hospital. She complained of swallowing problems,
      especially with solids. Following our dysphagia study protocol, we employed a
      speech pathologist and otolaryngology evaluation, mainly for clinical history,
      examination of anatomical structures involved with swallowing events, cranium
      nerves integrity and videoendoscopic swallowing study. We diagnosed severe
      oropharyngeal dysphagia, with aspiration of saliva and food of all consistencies.
      We advised against oral feeding and recommended a diet through a gastric tube.
      She started with therapy and xerostomia medication, together with the treatment
      of the base disease. The patient showed a significant improvement, noticed by the
      clinical evaluation and the control videoendoscopic swallowing study, with the
      possibility of returning to oral feeding. The authors stress the incidence of
      oropharyngeal dysphagia in dermatomyosites and suggest the videoendoscopic
      swallowing study as a good exam for diagnosis and follow-up of these patients.

PMID- 19582354
TI  - Cicatricial pemphygoid in the upper aerodigestive tract: report of two cases.
AB  - Cicatricial pemphygoid (mucous membrane cicatricial pemphygoid) is a chronic
      autoimmune inflammatory disease characterized by subepithelial bubbles in mucous
      membranes and, occasionally on the skin. It may affect the mouth, the nose,
      pharynx, larynx, the eyes, esophagus, anus, genitals and skin; especially
      affecting patients between fifty and sixty years of life. Treatment includes
      systemic steroids and immunosuppressive agents. In the present paper we describe
      two cases with the active disease, and one of them had sepsis because of using
      immunosuppressive agents and another that presented supraglottic stenosis
      requiring tracheostomy.

PMID- 19582355
TI  - Odontogenic myxoma of the maxilla invading the maxillary sinus.

PMID- 19582356
TI  - The importance of intraoral examination in the differential diagnosis of
      paracoccidioidomycosis.

PMID- 19582357
TI  - Glossopharyngeal schwannoma causing vocal fold paralysis.

PMID- 19582358
TI  - 34 self-inflicted foreign bodies in the maxillary sinus.

PMID- 19582360
TI  - Trace element hydrochemistry indicating water contamination in and around the
      Yangbajing geothermal field, Tibet, China.
AB  - Thirty-eight water samples were collected at Yangbajing to investigate the water
      contamination resulting from natural geothermal water discharge and anthropogenic
      geothermal wastewater drainage. The results indicate that snow or snow melting
      waters, Yangbajing River waters and cold groundwaters are free from geothermal
      water-related contamination, whereas Zangbo river waters are contaminated by
      geothermal wastewaters. Moreover, there may exist geothermal springs under the
      riverbed of a tributary stream of Zangbo River as shown by its Cd, Li, Mo and Pb
      concentrations. The efforts made in this study show trace element hydrochemistry
      can well indicate water quality degradation related to geothermal water
      exploitation.

PMID- 19582362
TI  - Anthropogenic sources of heavy metals in the Indian Ocean coast of Kenya.
AB  - Water and surface sediment samples from Rivers Sabaki, Ramisi and Vevesi that
      flow into the Indian Ocean coast of Kenya were analysed for heavy metals. The
      sediment concentrations of exchangeable cations (in microg/g) for Co, Cu, Mn, Ni,
      Pb, Sn and Zn ranged from 0.10 to 506.75 (for Mn at Sabaki), constituting between
      2% and 20% of the total metal concentrations obtained by digestion with strong
      acid. Cu, Mn, Ni, Pb and Zn were more leachable with 0.1 N HCl. The total
      dissolved metal in water and the total sediment concentrations for Ag, Cd, Co,
      Cr, Cu, Mn, Ni, Pb, Sn and Zn are given in the text. For dissolved metals, the
      metal/Mn ratios indicated higher concentrations of Ag in Sabaki River, Cd in
      Ramisi, Ni in Sabaki and Pb in Ramisi, respectively. In sediments, the metal/Mn
      ratios showed higher enrichment of Ag in Ramisi, Cd in Sabaki and Vevesi, and Zn
      in Sabaki, respectively. Enrichment factors showed elevated levels of Cd, Pb and
      Zn in sediment in River Sabaki and River Vevesi that were due to anthropogenic
      inputs through Athi River. The total dissolved metal concentration ranges for the
      three rivers were comparable with those ranges reported in rivers in South Africa
      but the sediment concentrations were below those of rivers in Europe and Asia
      where anthropogenic addition of some of the toxic elements such as Cu, Pb and Cd
      is evidently higher.

PMID- 19582361
TI  - Mechanism-based quantitative structure-activity relationships on toxicity of
      selected herbicides to Chlorella vulgaris and Raphidocelis subcapitata.
AB  - Four quantitative structure-activity relationships were developed for toxicity of
      selected photosynthesis (PHS) inhibitors and acetolactate synthase (ALS)
      inhibitors to Chlorella Vulgaris and Raphidocelis subcapitata using a mechanism
      based approach. These models have good fitness and predictive ability. The
      potential of electron transfer, intermolecular interactions with weak electron
      transfer, and intermolecular dispersive interactions between PHS inhibitors and
      the active site of action are key factors influencing the toxicity of these PHS
      inhibitors. Intermolecular weak electron-transfer interactions and intermolecular
      dispersive interactions mainly determine the toxicity of these ALS inhibitors.
      Sulfonyl is an important functional group governing the toxicity of ALS
      inhibitors investigated.

PMID- 19582363
TI  - Hyalella azteca (Saussure) responses to Coldwater River backwater sediments in
      Mississippi, USA.
AB  - Sediment from three Coldwater River, Mississippi backwaters was examined using 28
      day Hyalella azteca bioassays and chemical analyses for 33 pesticides, seven
      metals and seven PCB mixtures. Hydrologic connectivity between the main river
      channel and backwater varied widely among the three sites. Mortality occurred in
      the most highly connected backwater while growth impairment occurred in the other
      two. Precopulatory guarding behavior was not as sensitive as growth. Fourteen
      contaminants (seven metals, seven pesticides) were detected in sediments.
      Survival was associated with the organochlorine insecticide heptachlor.

PMID- 19582364
TI  - Evolution of potential ecological impacts of the bottom sediment from the Gulf of
      Gemlik; Marmara Sea, Turkey.
AB  - The eastern and southern coasts of the Gulf of Gemlik, a resort in the Sea of
      Marmara, Turkey, are under the influence of rapid ecotourism development, direct
      domestic and industrial discharges via rivers and outfalls, surface run-off,
      drainage from ports and shipping. According to sediment quality criteria in use
      around the world, sediment quality in the gulf shows a broad spectrum. It is more
      related by direct input, rather than by the type of sediment, and excluding inner
      port and southern coasts, it does not exert adverse biological effects yet. The
      total PAH concentrations range from 51 to 13,482 ng/g dry weight with the mean
      value of 1,850 ng/g dry weight (n = 61). The elevated values of the total toxic
      Benzo[a]pyrene equivalency (TEQcarc), with a maximum of 1,838 ng/g dry weight,
      were found at the inner harbor of Gemlik, possibly posing hazard to benthic
      organisms. Among the different PAHs, the contribution to the total TEQcarc
      decreased as the following order: Benzo[a]pyrene (43.6%) > Benzo[k]fluoranthene
      (36.0%) > Indeno[1,2,3-cd]pyrene (35.1%) > Benzo[b]fluoranthene (20.0%) >
      Chrysene + Triphenylene (18.9%) > Benzo[a]anthracene (12.5%).

PMID- 19582366
TI  - ERCP using double-balloon endoscopes in patients with Roux-en-Y anastomosis.
AB  - INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) and
      associated procedures are difficult to perform in patients with a Roux-en-Y
      reconstruction. Therefore, at present, at many institutions, ERCP is not
      generally performed for those with a Roux-en-Y anastomosis. METHODS: However,
      double-balloon endoscopes (DBEs) have dramatically changed this situation.
      RESULTS: The use of a DBE enables an endoscopic approach into the deeply situated
      small intestine, which has been difficult with a conventional endoscope.
      Therefore, ERCP for patients with a Roux-en-Y anastomosis has been attempted
      using a DBE, and good results have been reported. CONCLUSION: The development of
      DBEs has created the possibility of performing ERCP for patients with Roux-en-Y
      reconstruction in whom an endoscopic approach has conventionally been believed to
      be difficult.

PMID- 19582365
TI  - Predicting microvascular obstruction with cardiac troponin T after acute
      myocardial infarction: a correlative study with contrast-enhanced magnetic
      resonance imaging.
AB  - BACKGROUND: The presence of microvascular obstruction (MVO) is associated with
      more severely impaired left ventricular function and adverse prognosis. The aim
      of this study was to evaluate whether a single cardiac troponin T-value (cTnT)
      was able to predict the presence of MVO and whether cTnT is an independent
      predictor of MVO as compared to usual risk factors. STUDY DESIGN AND METHODS:
      Sixty-one consecutive patients with reperfused ST-elevation myocardial infarction
      (STEMI) were enrolled in the study. cTnT was measured serially at admission and
      after 24, 48, 72 and 96 h. Contrast-enhanced cardiac magnetic resonance imaging
      (CE-MRI) was performed on a 1.5T MR-scanner 4 +/- 1 days after STEMI. RESULTS:
      cTnT-time concentration kinetics in the presence of MVO differs from cTnT release
      in the absence of MVO showing a higher peak and a slower release. At single point
      measurement 24 h-cTnT correlates at least as well with the presence of MVO (P <
      0.001) as peak cTnT (P = 0.0016) and sampling over 96 h (P < 0.001). Using ROC
      analysis, at single measurement a cTnT concentration >2.52 microg/l at 24 h was a
      predictor for MVO (AUC 0.91) with a sensitivity of 100% and a specificity of 80%
      with a positive predictive value of 76% and a negative predictive value of 100%.
      In multivariate regression analysis 24 h-cTnT remained independent predictor for
      MVO. CONCLUSIONS: In STEMI, a single 24 h-cTnT value is an independent predictor
      for MVO and a convenient and inexpensive way to help define this important risk
      parameter in clinically routine.

PMID- 19582367
TI  - CTNNB1 (beta-catenin) mutation is rare in brain tumours but involved as a
      sporadic event in a brain metastasis.
AB  - BACKGROUND: The Wnt signaling pathway has been implicated in colon and other
      cancers. Nevertheless, few or no mutations of CTNNB1 (beta-catenin) have so far
      been described in brain cancer. We therefore examined the prevalence of
      constitutive activation of the Wnt signaling pathway in brain cancer specimens as
      well as cancer cell lines. METHOD: We used polymerase chain reaction PCR and
      direct sequencing methods to investigate whether mutations in the CTNNB1
      phosphorylation sites S33, S37, S41 and T45 were present in 68 brain tumours,
      including meningioma, astrocytoma, pituitary adenoma, neuroblastoma, metastasis
      to the brain, and cell lines. FINDINGS: CTNNB1 gene mutations were not found in
      either the original brain tumour specimens or the cell lines. However, a missense
      mutation of CTNNB1 was identified at residue 33, TCT (Ser) --> TGT (Cys) in a
      patient with lung metastasis to brain. In addition, in vitro functional assay
      showed that the S33C mutant of beta-catenin did affect transcriptional activity
      in a TCF-4-luciferase reporter construct. CONCLUSIONS: These results indicate
      that the mutation of exon 3 of the CTNNB1 gene in brain tumours may be a rare
      event and yet may be required for a small subset of human metastatic brain
      tumours.

PMID- 19582368
TI  - Stiffness in total knee arthroplasty.
AB  - Stiffness is a relatively uncommon complication after total knee arthroplasty. It
      has been defined as a painful limitation in the range of movement (ROM). Its
      pathogenesis is still unclear even if some risk factors have been identified.
      Patient-related conditions may be difficult to treat. Preoperative ROM is the
      most important risk factor, but an association with diabetes, reflex sympathetic
      dystrophy, and general pathologies such as juvenile rheumatoid arthritis and
      ankylosing spondylitis has been demonstrated. Moreover, previous surgery may be
      an additional cause of an ROM limitation. Postoperative factors include
      infections, arthrofibrosis, heterotrophic ossifications, and incorrect
      rehabilitation protocol. Infections represent a challenging problem for the
      orthopaedic surgeon, and treatment may require long periods of antibiotics
      administration. However, it is widely accepted that an aggressive rehabilitation
      protocol is mandatory for a proper ROM recovery and to avoid the onset of
      arthrofibrosis and heterotrophic ossifications. Finally, surgery-related factors
      represent the most common cause of stiffness; they include errors in soft-tissue
      balancing, component malpositioning, and incorrect component sizing. Although
      closed manipulation, arthroscopic and open arthrolysis have been proposed, they
      may lead to unpredictable results and incomplete ROM recovery. Revision surgery
      must be proposed in the case of well-documented surgical errors. These operations
      are technically demanding and may be associated with high risk of complications;
      therefore they should be accurately planned and properly performed.

PMID- 19582369
TI  - Progress in biomimetic carbohydrate recognition.
AB  - The importance of carbohydrate recognition in biology, and the unusual challenges
      involved, have lead to great interest in mimicking saccharide-binding proteins
      such as lectins. In this review, we discuss the design of artificial carbohydrate
      receptors, focusing on those which work under natural (i.e. aqueous) conditions.
      The problem is intrinsically difficult because of the similarity between
      substrate (carbohydrate) and solvent (water) and, accordingly, progress has been
      slow. However, recent developments suggest that solutions can be found. In
      particular, the "temple" family of carbohydrate receptors show good affinities
      and excellent selectivities for certain all-equatorial substrates. One example is
      selective for O-linked beta-N-acetylglucosamine (GlcNAc, as in the O-GlcNAc
      protein modification), while another is specific for beta-cellobiosyl and closely
      related disaccharides. Both show roughly millimolar affinities, matching the
      strength of some lectin-carbohydrate interactions.

PMID- 19582370
TI  - Oxidative stress triggers neuronal caspase-independent death: endonuclease G
      involvement in programmed cell death-type III.
AB  - To characterize neuronal death, primary cortical neurons (C57/Black 6 J mice)
      were exposed to hydrogen peroxide (H2O2) and staurosporine. Both caused cell
      shrinkage, nuclear condensation, DNA fragmentation and loss of plasma membrane
      integrity. Neither treatment induced caspase-7 activity, but caspase-3 was
      activated by staurosporine but not H2O2. Each treatment caused redistribution
      from mitochondria of both endonuclease G (Endo G) and cytochrome c. Neurons
      knocked down for Endo G expression using siRNA showed reduction in both nuclear
      condensation and DNA fragmentation after treatment with H2O2, but not
      staurosporine. Endo G suppression protected cells against H2O2-induced cell
      death, while staurosporine-induced death was merely delayed. We conclude that
      staurosporine induces apoptosis in these neurons, but severe oxidative stress
      leads to Endo G-dependent death, in the absence of caspase activation (programmed
      cell death-type III). Therefore, oxidative stress triggers in neurons a form of
      necrosis that is a systematic cellular response subject to molecular regulation.

PMID- 19582371
TI  - Phase I study of non-pegylated liposomal doxorubicin in combination with
      ifosfamide in adult patients with metastatic soft tissue sarcomas.
AB  - OBJECTIVE: The aim of this study was to evaluate the maximum tolerated dose (MTD)
      and safety of the combination of non- pegylated liposomal doxorubicin (Myocet)
      and ifosfamide in patients with metastatic soft tissue sarcomas. METHODS: Cohorts
      of four patients with metastatic soft tissue sarcomas received up to five cycles
      of intravenous ifosfamide 3000 mg/m2 on days 1- 3 in combination with escalating
      doses of intravenous Myocet on day 1 every 3 weeks until dose limiting toxicity
      (DLT) in at least one patient. Starting dose of Myocet was 40 mg/m2 to be
      escalated through 10 mg/m2 increase up to 80 mg/m2. Toxicity was graded according
      to the National Cancer Institute Common Toxicity Criteria v3.0 (NCI-CTC v3.0).
      RESULTS: Ten patients were enrolled in the study and 8 of them received the
      treatment. Median age was 45 years, 3 patients were male and 5 were female. DLT,
      consisting of neutropenic fever, was reached in one patient at dose level 2
      (Myocet 50 mg/m2). Therefore, the MTD and the recommended phase II dose is 40
      mg/m2. CONCLUSIONS: The combination of intravenous Myocet 40 mg/m2 on day 1 and
      ifosfamide 3,000 mg/m2 on days 1-3 every 3 weeks is safe and feasible; a phase II
      study is ongoing.

PMID- 19582372
TI  - Effect of a vitamin D(3) derivative (B3CD) with postulated anti-cancer activity
      in an ovarian cancer animal model.
AB  - The objective of the present study was to test the hypothesis that Calcidiol
      derivative B3CD qualifies as a potential anti-cancer drug in vivo employing an
      ovarian cancer xenograft model in mice. In addition, the selectivity of B3CD on
      viability and proliferation of platinum-resistant human ovarian cancer cell lines
      in comparison to control cell lines was analyzed in vitro. B3CD displayed cell
      line-specific cytotoxicity screened against a panel of ovarian and other
      carcinoma cell lines, endothelial and control cells. B3CD, at sub-cytotoxic
      concentrations, revealed stronger effects on the proliferation of SKOV-3 ovarian
      cancer cells vs. primary fibroblasts as determined by BrdU incorporation
      analysis. Treatment with B3CD at 0.5 microM resulted in highly condensed
      chromatin and fragmented nuclei in SKOV-3 cells but not in primary fibroblasts.
      B3CD induced cell death at low drug concentrations (< or = 0.5 microM) in SKOV-3
      ovarian cancer cells is mediated by the p38 MAPK signaling pathway: B3CD induced
      p38 MAPK expression and activation in SKOV-3 cells and inhibition of p38
      signaling counteracted B3CD induced cell death in vitro. An ovarian cancer cell
      animal model (human SKOV-3 cell derived xenografts in nude mice) revealed that
      tumor growth in few B3CD treated mice accelerated while the majority of B3CD
      treated mice displayed delayed tumor growth or full tumor regression. B3CD
      possesses anti-ovarian cancer properties in vitro and in vivo. We propose the
      further development of non-calcemic bromoacetoxy derivatives of vitamin D(3) as
      potential anti-cancer therapeutics.

PMID- 19582373
TI  - Effectiveness of temozolomide for primary glioblastoma multiforme in routine
      clinical practice.
AB  - Temozolomide has been used as a standard therapy for the treatment of newly
      diagnosed glioblastoma multiforme since 2005. To assess the effectiveness of
      temozolomide in routine clinical practice, we conducted an observational study at
      Maastricht University Medical Centre (MUMC). Data of patients receiving
      radiotherapy and temozolomide between January 2005 and January 2008 were
      retrieved from a clinical database (radiochemotherapy group), as were data of
      patients in a historical control group from the period before 2005 treated with
      radiotherapy only (radiotherapy group). The primary endpoint was overall
      survival. A total of 125 patients with GBM were selected to form the study
      cohort. Median survival benefit was 4 months: the median overall survival was 12
      months (95% CI, 9.7-14.3) in the group with radiochemotherapy with temozolomide,
      versus 8 months (95% CI, 5.3-10.7) in the group with only radiotherapy.
      Progression-free survival was 7 months (95% CI, 5.5-8.5) in the radiochemotherapy
      group and 4 months (95% CI, 2.9-5.1) in the group with only radiotherapy. The two
      year survival rate was 18% with radiochemotherapy with temozolomide against 4%
      with radiotherapy alone. Concomitant treatment with radiotherapy and temozolomide
      followed by adjuvant temozolomide resulted in grade III or IV haematological
      toxic effects in 9% of patients. The addition of temozolomide to radiotherapy in
      routine clinical practice for newly diagnosed glioblastoma resulted in a
      clinically meaningful survival benefit with minimal haematological toxicity,
      which confirms the experience of previous trials and justifies the continued use
      of temozolomide in routine clinical practice.

PMID- 19582375
TI  - The oxidative damage in lung of mice caused by lanthanoide.
AB  - This study was performed with the objective of assessing the antioxidant response
      of the lung of mice to different rare earths. LaCl(3), CeCl(3), and NdCl(3) at a
      higher dose of 20 mg/kg body weight were injected into the nasal cavity of ICR
      mice for consecutive 14 days, respectively. The increase of pulmonary lipids
      peroxide produced by Ln suggested an oxidative attack that was activated by a
      reduction of antioxidative defense mechanisms as measured by analyzing the
      activities of superoxide dismutase, catalase, ascorbate peroxidase, and total
      antioxidant capacity, as well as antioxidant levels such as glutathione and
      ascorbic acid, which were greatest in Ce(3+) treatment, medium in Nd(3+), and
      least in La(3+). It implied that the antioxidative responses of lung may be
      involved in 4f shell and alternable valence properties of Ln-induced lung
      toxicity.

PMID- 19582374
TI  - Detection of nanosecond time scale side-chain jumps in a protein dissolved in
      water/glycerol solvent.
AB  - In solution, the correlation time of the overall protein tumbling, tau(R), plays
      a role of a natural dynamics cutoff-internal motions with correlation times on
      the order of tau ( R ) or longer cannot be reliably identified on the basis of
      spin relaxation data. It has been proposed some time ago that the 'observation
      window' of solution experiments can be expanded by changing the viscosity of
      solvent to raise the value of tau(R). To further explore this concept, we
      prepared a series of samples of alpha-spectrin SH3 domain in solvent with
      increasing concentration of glycerol. In addition to the conventional (15)N
      labeling, the protein was labeled in the Val, Leu methyl positions ((13)CHD(2) on
      a deuterated background). The collected relaxation data were used in asymmetric
      fashion: backbone (15)N relaxation rates were used to determine tau(R) across the
      series of samples, while methyl (13)C data were used to probe local dynamics
      (side-chain motions). In interpreting the results, it has been initially
      suggested that addition of glycerol leads only to increases in tau(R), whereas
      local motional parameters remain unchanged. Thus the data from multiple samples
      can be analyzed jointly, with tau(R) playing the role of experimentally
      controlled variable. Based on this concept, the extended model-free model was
      constructed with the intent to capture the effect of ns time-scale rotameric
      jumps in valine and leucine side chains. Using this model, we made a positive
      identification of nanosecond dynamics in Val-23 where ns motions were already
      observed earlier. In several other cases, however, only tentative identification
      was possible. The lack of definitive results was due to the approximate character
      of the model-contrary to what has been assumed, addition of glycerol led to a
      gradual 'stiffening' of the protein. This and other observations also shed light
      on the interaction of the protein with glycerol, which is one of the naturally
      occurring osmoprotectants. In particular, it has been found that the overall
      protein tumbling is controlled by the bulk solvent, and not by a thin solvation
      layer which contains a higher proportion of water.

PMID- 19582376
TI  - Study on the trace elements in Swertia chirayita (Roxb.) H. Karsten.
AB  - An attempt has been made to analyze some trace elements and electrolytes like Zn,
      Cu, Mn, Fe, Co, Na, K, Ca, and Li present in the Swertia chirayita roots and
      leaves. The concentration of Ca in all the samples was more than 1,346.0 mg/kg
      and the concentration of other elements was found in the order K > Ca > Fe > Na >
      Mn > Zn > Co > Cu > Li in different samples of S. chirayita.

PMID- 19582377
TI  - Dialysability of magnesium and calcium from hospital duplicate meals: influence
      exerted by other elements.
AB  - Total and dialysable magnesium and calcium levels and corresponding
      dialysabilities were measured in duplicate meals (n = 108) during 36 consecutive
      days. The interaction exerted by other nutrients and energy on them was also
      performed. Total mean magnesium and calcium fractions of 113.9 +/- 98.3 and 337.2
      +/- 278.9 mg/meal respectively, were found. The Mg and Ca levels supplied by
      meals are positively (p < 0.05) correlated with macronutrient contents
      (carbohydrates and proteins). The mean dialysable Mg and Ca fractions were 56.9
      +/- 36.3 and 127.4 +/- 112.3 mg/meal (50.4 +/- 13.2 and 37.8 +/- 10.7% as
      dialysabilities, respectively). Total Mg and Ca levels are significantly
      correlated with corresponding element dialysabilities (p < 0.05). For both
      minerals, significant correlations between their total and dialysable fractions
      and between their dialysable level and dialysabilities were noted (p < 0.01). The
      mean Mg and Ca daily dietary intakes (DDI) were 341.7 +/- 68.0 and 1,011.6 +/-
      424.4 mg/day, respectively. For Ca and Mg the existence of similarities in their
      behaviour in meals and absorptive processes has been found. Duplicate meals with
      raw vegetables are good sources of bioaccessible Mg. High Ca dialysability has
      been found in the analysed meals. The fish and products constitute a good source
      of bioaccessible Ca. Mg, Ca, zinc, and chromium levels enhanced significantly the
      Mg dialysability. The Ca dialysability rose significantly with dialysable Ca and
      chromium fractions (p < 0.05).

PMID- 19582378
TI  - Nail antioxidant trace elements are inversely associated with inflammatory
      markers in healthy young adults.
AB  - Antioxidant intake may be linked to a reduction of the chronic low-grade
      inflammatory state related to obesity and several accompanying disorders such as
      insulin resistance, cardiovascular diseases, and metabolic syndrome. So, the aim
      of this study was to evaluate the potential associations between nail trace
      elements and several indicators in healthy young adults, emphasizing on the
      putative effect of antioxidant trace element intake on inflammation-related
      marker concentrations. This study enrolled 149 healthy young adults, whose
      anthropometrical and blood pressure values as well as lifestyle features were
      analyzed. Fasting blood samples were collected for the biochemical and
      inflammation-related measurements (C-reactive protein, tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-6, IL-18, and homocysteine). Nail samples
      were collected for the analysis of selenium, zinc, and copper concentrations. Our
      results showed that nail selenium was negatively associated with IL-18; nail zinc
      concentrations were inversely related to circulating IL-6, IL-18, and TNF-alpha,
      whereas nail copper (Cu) and Cu/selenium values were negatively correlated with
      homocysteine levels and the Cu/zinc ratio was unaffected. In conclusion, nail
      content on some trace elements related to antioxidant defense mechanisms seems to
      be associated with several inflammation-related markers linked to chronic
      diseases in apparently healthy young adults, which is of interest to understand
      the role of antioxidant intake.

PMID- 19582379
TI  - Comparative analysis of serum manganese, zinc, calcium, copper and magnesium
      level in panic disorder patients.
AB  - The purpose of the study was to determine the serum concentration of trace
      elements of panic disorder patients and to find out the relationship between
      trace element levels and nutritional status or socio-economic factors. The study
      was conducted among 54 panic disorder patients and 52 healthy volunteers.
      Patients were recruited from Bangabandhu Sheikh Mujib Medical University by
      random sampling. Serum trace element concentrations were determined by flame
      atomic absorption spectroscopy (for Mg, Zn, Ca, and Cu) as well as graphite
      furnace (for Mn). Data were analyzed by independent t test, Pearson's correlation
      analysis, regression analysis, and ANOVA. The serum concentration of Mn, Zn, Ca,
      Cu, and Mg in panic disorder patients were 0.37 +/- 0.30, 0.67 +/- 0.20, 99.91 +/
      15.15, 0.83 +/- 0.23, and 21.14 +/- 3.72 mg/L, while those were 0.4163 +/-
      0.2527, 0.86 +/- 0.3, 106.6073 +/- 18.6531, 0.8514 +/- 0.3646, and 21.37 +/- 2.03
      mg/L in control subjects, respectively. The serum concentration of Zn decreased
      significantly (p = 0.001) in patient group. But the differences of the
      concentration of Mn, Ca, Cu, and Mg between patient and control group were not
      significant (p = 0.522, p = 0.065, p = 0.800, and p = 0.712, respectively). Socio
      economic data reveal that most of the patients were very poor and middle aged.
      Mean BMIs of the control group (23.74 +/- 2.71 kg/m(2)) and the patient group
      (22.62 +/- 3.74 kg/m(2)) were within the normal range (18.5-25.0 kg/m(2)). There
      was no significant relationship between serum zinc level and BMI of patients (r =
      0.038; p = 0.809). So the decreased level of serum zinc in panic disorder
      patients was not because of other reasons, but rather it may provide a prognostic
      tool for the diagnosis and treatment of this disease.

PMID- 19582381
TI  - Prophylactic Burch colposuspension at the time of abdominal sacrocolpopexy: a
      survey of current practice patterns.
AB  - INTRODUCTION: The purpose of this study was to determine the utilization of the
      prophylactic Burch procedure with abdominal sacrocolpopexy since the publication
      of the Colpopexy and Urinary Reduction Efforts (CARE) trial. METHODS: Using an
      Internet survey, 1,134 members of the American Urogynecological Society (AUGS)
      were contacted in May 2008 and questioned regarding their practice patterns to
      prevent de novo stress incontinence after sacrocolpopexy. RESULTS: Two hundred
      sixty-six responses were obtained for a 23% response rate. Of the 235 respondents
      actively performing sacrocolpopexies, 133 (57%) would not perform a prophylactic
      Burch colposuspension at the time of sacrocolpopexy in a woman without symptoms
      of stress urinary incontinence. Respondents were more likely to perform a
      prophylactic Burch if it had been more than 6 years since they completed
      residency or fellowship training. CONCLUSIONS: Prophylactic Burch colposuspension
      at the time of abdominal sacrocolpopexy has not been uniformly implemented into
      clinical practice by AUGS members since the publication of the CARE Trial.

PMID- 19582382
TI  - Vaginal noise: prevalence, bother and risk factors in a general female population
      aged 45-85 years.
AB  - INTRODUCTION AND HYPOTHESIS: Vaginal noise (VN) is a symptom of pelvic floor (PF)
      dysfunction and has been described in a few studies. No other risk factors have
      been described besides parity and pelvic organ prolapse (POP). Underlying
      mechanisms of VN are unclear. Aims of this study were to describe prevalence,
      bother and relation between VN and PF (muscle)(dys)function. METHODS: A cross
      sectional study was performed on a general population of 2,921 women (aged 45-85
      years). Questionnaires were filled in by 1,397 women, and 800 were selected at
      random to undergo vaginal examination for POP Quantification and PF muscle
      function assessment. Chi-square tests, Student's t test and multivariate logistic
      regression were performed (P < 0.05). RESULTS: Response rate was 62.7%.
      Prevalence of VN was 12.8%; 72.1% reported only a little bother. Odds ratios for
      parity and solid stool were high. CONCLUSIONS: VN was strongly related to many
      symptoms of pelvic floor dysfunction, but it was only causing a little bother.

PMID- 19582383
TI  - Complications of transvaginal monofilament polypropylene mesh in pelvic organ
      prolapse repair.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to document intraoperative and
      postoperative complications associated with the use of transvaginal polypropylene
      mesh in the repair of pelvic organ prolapse (POP). METHODS: This is a
      retrospective review of 127 cases of transvaginal repair of POP using synthetic
      mesh. RESULTS: Mean postoperative value (+/-SD) for pelvic organ prolapse
      quantification (POPQ) measurements Aa, Ap, and C were: -2.4 +/- 1.1 (cm), -2.4 +/
      0.9 (cm), and -7.7 +/- 1.2 (cm), respectively. The difference between
      preoperative and postoperative values of these points was significant (p <
      0.0001). Mesh erosion rate was 13/127 (10.2%) with significant correlation
      between mesh erosion and concurrent vaginal hysterectomy (p = 0.008). Combined
      anterior and posterior vaginal mesh surgery increased the risk of intraoperative
      bleeding and blood transfusion (p < 0.05). CONCLUSIONS: Concurrent vaginal
      hysterectomy is associated with increased risk of vaginal mesh erosion. Combined
      anterior and posterior vaginal mesh repair is an increased risk factor for
      intraoperative bleeding and blood transfusion.

PMID- 19582384
TI  - Prophylactic antibiotics to prevent urinary tract infection during clean
      intermittent self-catheterization (CISC) for management of voiding dysfunction
      after prolapse and incontinence surgery: a decision analysis.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to estimate efficacy
      of prophylactic antibiotics in UTI prevention during CISC for postoperative
      voiding dysfunction after prolapse/incontinence surgery. METHODS: We constructed
      a decision tree model to evaluate risks and benefits of prophylactic antibiotics
      during CISC for voiding dysfunction after prolapse/incontinence surgery. The
      model randomized women requiring CISC to prophylactic antibiotics or no
      prophylaxis. Probabilities for UTI after CISC with or without prophylactic
      antibiotics, sequelae from antibiotic use or UTI, and utility values were
      obtained from published literature and practice quality assurance reviews. Main
      outcome was probability of experiencing no UTI or adverse event. RESULTS: Under
      baseline assumptions, prophylactic antibiotics were favored in both models. In
      the true UTI model, prophylactic antibiotics had an 83.1% probability of no UTI
      or adverse events; 16.1% better than no prophylactic antibiotics. CONCLUSIONS:
      Using decision analysis methods, prophylactic antibiotics are favored for
      prevention of UTI during CISC to manage voiding dysfunction after
      prolapse/incontinence surgery.

PMID- 19582385
TI  - Female urethral diverticulum: a pathological insight.
AB  - INTRODUCTION AND HYPOTHESIS: In this study, we define the histopathological
      features of female urethral diverticula and attempt to elucidate its pathogenesis
      and etiology. METHODS: We analyzed 22 clinical records of women diagnosed with
      urethral diverticula. We collected clinical, surgical, and pathological data.
      Pathological re-assessment was performed using hematoxylin-eosin and van Gieson
      stains. RESULTS: The predominant epithelial types were squamous (41.9%), columnar
      (31.8%), combined squamous and columnar (18.2%), and cuboidal (13.6%). There was
      no case of the transitional type. Epithelial ulcerations were present in nine
      cases. The diverticular wall was composed only of fibrous collagen tissue in all
      cases. Inflammatory signs were noted in 77.3% of specimens. CONCLUSIONS:
      Histopathological features of female urethral diverticula match the criteria for
      paraurethral cysts. Concomitant use of synthetic meshes should be avoided due to
      the possibility of an infectious etiology. Transvaginal excision of the sac is
      recommended, while transurethral procedures are contraindicated.

PMID- 19582386
TI  - Comparative results of two techniques to treat stress urinary incontinence:
      synthetic transobturator and aponeurotic slings.
AB  - INTRODUCTION AND HYPOTHESIS: This study aims to analyze comparatively the
      efficacy and safety of synthetic transobturatory and aponeurotic retropubic
      slings, in the treatment of stress urinary incontinence (SUI) in women. METHODS:
      Patients were separated in a randomized way. Twenty-one patients were submitted
      to the operatory correction by the transobturatory sling technique, whereas 20
      patients were operated by the retropubic sling technique. All patients were
      submitted to complete physical exam and urodynamic test. The "T" test and the
      Mann-Whitney U test were applied to establish comparisons between the two groups.
      Patients were followed-up for 12 months. RESULTS: Healing rate was 90.5% (19/21)
      and 95% (19/20), respectively after 12 months. The transobturatory group
      presented lesser complications rate than the retropubic group. CONCLUSIONS: The
      transobturatory and the aponeurotic slings techniques were equally effective for
      the treatment of SUI. The transobturatory sling has shown fewer complications and
      lesser surgical time than the aponeurotic sling technique.

PMID- 19582387
TI  - Caldesmon expression is decreased in women with anterior vaginal wall prolapse: a
      pilot study.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to compare vaginal
      caldesmon expression in women with and without anterior vaginal wall prolapse.
      METHODS: Vaginal tissues were sampled in women with (n = 11) or without (n = 11)
      vaginal wall prolapse. Caldesmon messenger RNA (mRNA) expression was assessed by
      quantitative real-time polymerase chain reaction. Immunohistochemistry and
      digital image analysis were used to determine caldesmon protein expression in the
      histologic sections. RESULTS: There were no significant differences in
      demographic data between the two groups. Caldesmon mRNA expression was
      significantly decreased in the vaginal tissue from women with anterior vaginal
      wall prolapse compared to women without prolapse [(caldesmon mean +/- SD mRNA
      expression in relative units) 0.03 +/- 0.03 vs 0.17 +/- 0.17, P = 0.02]. The
      fractional area of nonvascular caldesmon staining in the vagina of women with
      anterior vaginal wall prolapse was significantly decreased compared to women
      without prolapse [mean +/- SD (0.09 +/- 0.04 vs 0.16 +/- 0.09, P = 0.03)].
      CONCLUSIONS: Vaginal caldesmon expression is significantly decreased in women
      with anterior vaginal wall prolapse compared to normal subjects.

PMID- 19582394
TI  - WNT/beta-catenin increases the production of incretins by entero-endocrine cells.
AB  - AIMS/HYPOTHESIS: Glucose-dependent insulinotropic peptide (GIP) plays a pivotal
      role in the regulation of glucose homeostasis. Rates of diet-induced obesity,
      insulin resistance and type 2 diabetes are decreased when GIP signalling is
      disturbed in mice, suggesting that GIP plays a role in the onset of type 2
      diabetes. WNT signalling is linked to type 2 diabetes and induces synthesis of
      the other incretin, glucagon-like peptide 1 (GLP-1). GLP-1 analogues improve
      treatment of type 2 diabetes patients in whom GLP-1 signalling is intact and have
      captured clinical attention. GIP levels are altered at the onset of type 2
      diabetes and later on, while GIP signalling is impaired. Thus, GIP is not a
      candidate for treatment but might be an important target from a prevention
      perspective. Hypothesising that hypersecretion of GIP links altered WNT
      signalling to the onset of type 2 diabetes, we sought to determine whether WNT
      signalling induces GIP production by entero-endocrine cells. METHODS: RT-PCR and
      chromatin immunoprecipitation (ChIP) were used to study Gip gene induction. Gip
      promoter elements mediating WNT/lithium induction were identified
      (electrophoretic mobility shift assay, co-transfection of deletion mutants,
      ChIP). RESULTS: Lithium or WNT/beta-catenin signalling enhanced GIP production by
      entero-endocrine cells through a conserved site in the proximal Gip promoter.
      Lithium favours lymphoid enhancer factor-1/beta-catenin binding to Gip promoter
      and diminishes ChIP through T cell factor-4 and histone deacetylase 1.
      CONCLUSIONS/INTERPRETATION: Lithium and WNT are incretin inducers in general.
      This work provides a novel link between WNT signalling, obesity and diabetes.

PMID- 19582396
TI  - The 'Consent to Research' paradigm in critical care: challenges and potential
      solutions.

PMID- 19582395
TI  - Decreased surfactant phosphatidylcholine synthesis in neonates with congenital
      diaphragmatic hernia during extracorporeal membrane oxygenation.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) may result in severe respiratory
      insufficiency with a high morbidity. The role of a disturbed surfactant
      metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous
      surfactant metabolism in the most severe CDH patients who required extracorporeal
      membrane oxygenation (ECMO). METHODS: Eleven neonates with CDH who required ECMO
      and ten ventilated neonates without significant lung disease received a 24-h
      infusion of the stable isotope [U-(13)C] glucose. The (13)C-incorporation into
      palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial
      tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid
      (ELF) was measured during the first 4 days of the study. RESULTS: Fractional
      surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls
      (2.4 +/- 0.33 vs. 8.0 +/- 2.4%/day, p = 0.04). The control group had a higher
      maximal enrichment (0.18 +/- 0.03 vs. 0.09 +/- 0.02 APE, p = 0.04) and reached
      this maximal enrichment earlier (46.7 +/- 3.0 vs. 69.4 +/- 6.6 h, p = 0.004)
      compared to the CDH-ECMO group, which reflects higher and faster precursor
      incorporation in the control group. Surfactant PC concentration in ELF was
      similar in both groups. CONCLUSION: These results show that CDH patients who
      require ECMO have a decreased surfactant PC synthesis, which may be part of the
      pathogenesis of severe pulmonary insufficiency and has a negative impact on
      weaning from ECMO.

PMID- 19582397
TI  - A quantitative climate-match score for risk-assessment screening of reptile and
      amphibian introductions.
AB  - Assessing climatic suitability provides a good preliminary estimate of the
      invasive potential of a species to inform risk assessment. We examined two
      approaches for bioclimatic modeling for 67 reptile and amphibian species
      introduced to California and Florida. First, we modeled the worldwide
      distribution of the biomes found in the introduced range to highlight similar
      areas worldwide from which invaders might arise. Second, we modeled potentially
      suitable environments for species based on climatic factors in their native
      ranges, using three sources of distribution data. Performance of the three
      datasets and both approaches were compared for each species. Climate match was
      positively correlated with species establishment success (maximum predicted
      suitability in the introduced range was more strongly correlated with
      establishment success than mean suitability). Data assembled from the Global
      Amphibian Assessment through NatureServe provided the most accurate models for
      amphibians, while ecoregion data compiled by the World Wide Fund for Nature
      yielded models which described reptile climatic suitability better than available
      point-locality data. We present three methods of assigning a climate-match score
      for use in risk assessment using both the mean and maximum climatic
      suitabilities. Managers may choose to use different methods depending on the
      stringency of the assessment and the available data, facilitating higher
      resolution and accuracy for herpetofaunal risk assessment. Climate-matching has
      inherent limitations and other factors pertaining to ecological interactions and
      life-history traits must also be considered for thorough risk assessment.

PMID- 19582404
TI  - The paradoxical cell biology of alpha-Synucle.
AB  - Synucleinopathies are a group of neurodegenerative diseases characterized by
      accumulation and aggregation of the protein alpha-synuclein in neuronal perikarya
      and processes. In contrast to the proximal localization of alpha-synuclein in
      diseased states, under physiologic conditions, the bulk of alpha-synuclein is
      present in distant presynaptic terminals. Thus, pathologic conditions lead to
      mislocalization and aggregation of alpha-synuclein in neuronal cell bodies, and
      an outstanding question relates to the cell-biological mechanisms that can lead
      to such mislocalization. Like most other synaptic proteins, alpha-synuclein is
      synthesized in the neuronal perikarya and then transported into axons and
      synaptic domains. Accordingly, it has been hypothesized that disturbances in
      biogenesis/axonal transport or presynaptic targeting of alpha-synuclein can lead
      to its mislocalization in diseased states. In this chapter, key observations that
      lead to this hypothesis are presented in addition to a review of some recent
      literature that has directly addressed this issue. Finally, conflicting results
      that have resulted from such studies are also highlighted, and a view is offered
      to reconcile these controversies.

PMID- 19582405
TI  - Antigen processing and presentation in multiple sclerosis.
AB  - CD4(+) T cells play a central role in the pathogenesis of multiple sclerosis
      (MS). Generation, activation and effector function of these cells crucially
      depends on their interaction with MHC II-peptide complexes displayed by antigen
      presenting cells (APC). Processing and presentation of self antigens by different
      APC therefore influences the disease course at all stages. Selection by thymic
      APC leads to the generation of autoreactive T cells, which can be activated by
      peripheral APC. Reactivation by central nervous system APC leads to the
      initiation of the inflammatory response resulting in demyelination. In this
      review we will focus on how MHC class II antigenic epitopes are created by
      different APC from the thymus, the periphery and from the brain, and will discuss
      the relevance of the balance between creation and destruction of such epitopes in
      the context of MS. A solid understanding of these processes offers the
      possibility for designing future therapeutic strategies.

PMID- 19582406
TI  - Cooperation of B cells and T cells in the pathogenesis of multiple sclerosis.
AB  - B cells and T cells are two major players in the pathogenesis of multiple
      sclerosis (MS) and cooperate at various check points. B cells, besides serving as
      a source for antibody-secreting plasma cells, are efficient antigen presenting
      cells for processing of intact myelin antigen and subsequent activation and pro
      inflammatory differentiation of T cells. This notion is supported by the
      immediate clinical benefit of therapeutic B cell depletion in MS, presumably
      abrogating development of encephalitogenic T cells. However, different B cell
      subsets strongly vary in their respective effect on T cell differentiation which
      may relate to B cell phenotype, activation status, antigen specificity and the
      immunological environment where a B cell encounters a naive T cell in. In this
      regard, some B cells also have anti-inflammatory properties producing regulatory
      cytokines and facilitating development and maintenance of other immunomodulatory
      immune cells, such as regulatory T cells. Reciprocally, differentiated T cells
      influence T cell polarizing B cell properties establishing a positive feedback
      loop of joint pro- or anti-inflammatory B and T cell developments. Further, under
      the control of activated T helper cells, antigen-primed B cells can switch
      immunoglobulin isotype, terminally commit to the plasma cell pathway or enter the
      germinal center reaction to memory B Cell development. Taken together, B cells
      and T cells thus closely support one another to participate in the pathogenesis
      of MS in an inflammatory but also in a regulatory manner.

PMID- 19582407
TI  - Mitochondrial transport dynamics in axons and dendrites.
AB  - Mitochondrial dynamics and transport have emerged as key factors in the
      regulation of neuronal differentiation and survival. Mitochondria are dynamically
      transported in and out of axons and dendrites to maintain neuronal and synaptic
      function. Transport proceeds through a controlled series of plus- and minus-end
      directed movements along microtubule tracks (MTs) that are often interrupted by
      short stops. This bidirectional motility of mitochondria is facilitated by plus
      end-directed kinesin and minus end-directed dynein motors, and may be coordinated
      and controlled by a number of mechanisms that integrate intracellular signals to
      ensure efficient transport and targeting of mitochondria. In this chapter, we
      discuss our understanding of mechanisms that facilitate mitochondrial transport
      and delivery to specific target sites in dendrites and axons.

PMID- 19582409
TI  - Ubiquitination and TNFR1 signaling.
AB  - Death receptors are a subset of the tumor necrosis factor receptor (TNFR) family
      of proteins and share a characteristic cytoplasmic motif called the "death
      domain". In addition to mediating cell death, these receptors regulate cell
      proliferation, inflammatory responses, and tumor progression. Receptor occupancy
      triggers the assembly of several cytoplasmic molecules into distinct complexes,
      each initiating separate signaling events leading to different biological
      responses. Post-translational modifications involving ubiquitin, a peptide of 76
      amino acids, regulate events at nearly all stages of signaling. All ubiquitin
      chains function as docking platforms for molecules with specific recognition
      motifs that either propagate the signal or target the protein for proteasomal
      degradation. Moreover, enzymes with ubiquitin thioesterase activity
      (deubiquitinating enzymes, or DUBs) reverse modifications by removing the
      ubiquitin chains, allowing ubiquitin editing at the molecular level. Ubiquitin
      protein ligases (E3s), DUBs, and signaling molecules with ubiquitin recognition
      motifs control TNFR1 mediated cell death and activation of NF-kappaB and JNK.
      Here, we discuss the current understanding of how these proteins regulate TNFR1
      signaling.

PMID- 19582410
TI  - Targeting death-receptors in radiation therapy.
AB  - The development of apoptosis resistance is a crucial step during the pathogenesis
      of malignant tumors. Thus, any treatment approach overcoming apoptosis resistance
      may be a valuable tool in oncology. Although a variety of treatments induce
      apoptosis, only very few specifically trigger programmed cell death. In this
      regard, the class of apoptosis inducing ligands may turn out to have a
      considerable potential in oncology. TNF-alpha-related apoptosis-inducing ligand
      (TRAIL/Apo2L) is the most promising candidate, either alone or in combination
      with established cancer therapies, since it induces apoptosis in a wide range of
      malignant cells while sparing most normal tissues. Since death-receptor induced
      apoptosis is mainly mediated via nonmitochondrial death pathways, it is possible
      to induce apoptosis in cancer cell systems which mainly harbor defects within the
      mitochondrial death cascades. Even more so it has been shown that conventional
      DNA damaging approaches reduced the killing threshold for receptor induced
      apoptosis, making TRAIL an ideal candidate for combined approaches. Thus,
      combined treatments might offer the chance to enhance therapeutic efficiency and
      overcome resistance. In combination, additive or synergistic apoptotic responses
      and substantially enhanced clonogenic cell kill has been documented. Furthermore,
      in several settings it has been shown that combined modality teatments were
      effective in malignant cells, which are highly resistant to either treatment,
      alone. Ionizing radiation is one of the most effective modalities in oncology.
      Thus, it is reasonable to test, how far combinations of TRAIL with ionizing
      radiation may increase the efficacy. Indeed, the combination of TRAIL with
      ionizing radiation in several in vitro settings as well as xenograft models
      resulted in highly increased rates of cell kill and long-term tumor control. No
      increase in the rate and severity of side effects has been documented, indicating
      that the combination really increases the therapeutic ratio. It is important to
      note that TRAIL and TRAIL receptor agonistic antibodies, either as single

PMID- 19582408
TI  - Axon regeneration in the peripheral and central nervous systems.
AB  - Axon regeneration in the mature mammalian central nervous system (CNS) is
      extremely limited after injury. Consequently, functional deficits persist after
      spinal cord injury (SCI), traumatic brain injury, stroke, and related conditions
      that involve axonal disconnection. This situation differs from that in the
      mammalian peripheral nervous system (PNS), where long-distance axon regeneration
      and substantial functional recovery can occur in the adult. Both extracellular
      molecules and the intrinsic growth capacity of the neuron influence regenerative
      success. This chapter discusses determinants of axon regeneration in the PNS and
      CNS.

PMID- 19582411
TI  - Regulation of mRNA transport and translation in axons.
AB  - Movement of mRNAs into axons occurs by active transport by microtubules through
      the activity of molecular motor proteins. mRNAs are sequestered into granular
      like particles, referred to as transport ribonucleoprotein particles (RNPs) that
      mediate transport into the axonal compartment. The interaction of mRNA binding
      proteins with targeted mRNA is a key event in regulating axonal mRNA localization
      and subsequent localized translation of mRNAs. Several growth-modulating stimuli
      have been shown to regulate axonal mRNA localization. These do so by activating
      specific intracellular signaling pathways that converge upon RNA binding proteins
      and other components of the transport RNP to regulate their activity
      specifically. Transport can be both positively and negatively regulated by
      individual stimuli with regard to individual mRNAs. Consequently, there is
      exquisite specificity for regulating the axon's composition of mRNAs and proteins
      that control expression in the axon. Finally, recent studies indicate that
      axotomy can also trigger changes in axonal mRNA composition by specifically
      shifting the populations of mRNAs that are transported into distal axons.

PMID- 19582412
TI  - Actin in axons: stable scaffolds and dynamic filaments.
AB  - Actin filaments are thin polymers of the 42 kD protein actin. In mature axons a
      network of subaxolemmal actin filaments provide stability for membrane integrity
      and a substrate for short distance transport of cargos. In developing neurons
      dynamic regulation of actin polymerization and organization mediates axonal
      morphogenesis and axonal pathfinding to synaptic targets. Other changes in axonal
      shape, collateral branching, branch retraction, and axonal regeneration, also
      depend on actin filament dynamics. Actin filament organization is regulated by a
      diversity of actin-binding proteins (ABP). ABP are the focus of complex extrinsic
      and intrinsic signaling pathways, and many neurological pathologies and
      dysfunctions arise from defective regulation of ABP function.

PMID- 19582413
TI  - Retrograde injury signaling in lesioned axons.
AB  - The cell body of a lesioned neuron must receive accurate and timely information
      on the site and extent of axonal damage, in order to mount an appropriate
      response. Specific mechanisms must therefore exist to transmit such information
      along the length of the axon from the lesion site to the cell body. Three
      distinct types of signals have been postulated to underlie this process, starting
      with injury-induced discharge of axon potentials, and continuing with two
      distinct types of retrogradely transported macromolecular signals. The latter
      includes, on the one hand, an interruption of the normal supply of retrogradely
      transported trophic factors from the target, and, on the other hand, activated
      proteins originating from the injury site. This chapter reviews the progress on
      understanding the different mechanistic aspects of the axonal response to injury,
      and how the information is conveyed from the injury site to the cell body to
      initiate regeneration.

PMID- 19582414
TI  - The genetics of multiple sclerosis.
AB  - After many years of slow progress in the genetic analysis of complex diseases,
      including multiple sclerosis (MS), the past few years have eventually seen the
      first steps of turning a frustrating quest into a success story with the
      identification of a rapidly increasing number of confirmed disease promoting or
      protecting genetic variants. The principal reason for the change in situation is
      numbers: number of individuals assessed in the studies and number of genetic
      variations available for genotyping. In short, we now know that it takes
      thousands of patients to identify new genes but also to pinpoint the complex
      interplay of several genetic factors within the strongest genetic locus in MS,
      the HLA gene complex. However, the mission is not completed until the gene
      identification has been translated into useful understanding of disease
      mechanisms, and this is likely to necessitate further methodological progress as
      well as hard work in functional studies. Obviously, the reason for gene
      identification is never going to be genetic counseling or prenatal diagnosis as
      not even full knowledge of the genetic background on MS will allow even 30%
      accuracy in disease prediction, i.e., the concordance rate in female monozygotic
      twins. Therefore, it is only in the way that risk genes reveal details of disease
      triggering events, or that severity genes influence mechanisms driving the tissue
      damage, that genetic information is likely to be useful.

PMID- 19582415
TI  - T-cells in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a multifocal demyelinating disease of the central
      nervous system pathologically characterized by lesions of infiltrating
      macrophages and T cells. Multiple lines of evidence implicate that T cells play a
      central role in both mediating and regulating MS pathophysiology, and efforts to
      develop rational therapeutic strategies for MS have focused on understanding
      factors which control T cell function. T cells are a highly heterogeneous
      population comprised of multiple cell subtypes which mediate both adaptive
      immunity and specific tolerance. Much has been learned about the molecular
      signals that induce T cell activation and differentiation, and several effective
      treatments for MS act by altering these activation and differentiation pathways.
      In recent years, increasing recognition has been given to T cell subsets which
      serve immunosuppressive or regulatory functions, and it has been discovered that
      patients with MS have a functional defect in these cells. Current work is
      beginning to shed light on interactions of pathogenic and regulatory T cells with
      the intrinsic cells of the CNS to provide a more comprehensive picture of MS
      pathogenesis.

PMID- 19582416
TI  - Role of NK cells and invariant NKT cells in multiple sclerosis.
AB  - Natural killer (NK) cells and invariant natural killer T (iNKT) cells are two
      distinctive lymphocyte populations, each possessing its own unique features.
      Although NK cells are innate lymphocytes with cytotoxic property, they play an
      immunoregulatory role in the pathogenesis of autoimmune diseases. NKT cells are T
      cells expressing invariant TCR a-chains, which are known to bridge innate and
      adaptive arms of the immune system. Accumulating data now support active
      involvement of these cells in multiple sclerosis (MS). However, unlike
      professionally committed regulatory cells such as Foxp3(+) regulatory T cells,
      NK, and iNKT cells have dual potential of acting as either protective or
      pathogenic lymphocytes depending on the disease setting, adding complexity to the
      interpretation of data obtained from human and rodent studies. They are potential
      therapeutic targets in MS, and further in-depth understanding of these cells will
      lead to designing new strategies to overcome the disabling disease MS.

PMID- 19582418
TI  - Analysis of cancer stem cell metastasis in xenograft animal models.
AB  - Metastatic spread of cancer cells from the primary tumors to distant vital
      organs, such as lung, liver, brain, and bone, is responsible for the majority of
      cancer-related deaths. Cancer stem cells are likely to play essential roles in
      the metastatic spread of primary tumors because of their self-renewal capability
      and their potential to give rise to differentiated progenies that can adapt to
      different target organ microenvironments. Investigating the metastatic behavior
      of cancer stem cells (CSCs) is critical for the development of more effective
      therapies to prevent or delay the progression of malignant diseases. Animal
      models have been developed to mimic the multistep process of metastasis to
      various target organs. In this chapter, I will describe several xenograft methods
      to introduce human breast cancer cells into nude mice in order to generate
      spontaneous and experimental metastases. Similar experimental approach can be
      applied to analyze the metastatic behavior of CSCs derived from other tumor
      types.

PMID- 19582417
TI  - Defining cancer stem cells by xenotransplantation in zebrafish.
AB  - The zebrafish (Danio rerio) has become an increasingly utilized and relevant
      model organism in the study of cancer. The use of transgenic and reverse genetic
      approaches has yielded several strains that model a variety of human neoplasms.
      In addition to modeling human disease, these strains provide a platform for the
      analysis of tumor stem cells. Here we describe the basic technique for the
      isolation and transplantation of tumor tissue in the zebrafish. This technique
      was designed to study metastasis and invasive potential of zebrafish tumor cells.
      Additionally, the basic protocol can be modified in order to describe cancer stem
      cell characteristics, including proliferative capacity, self-renewal, and the
      minimum number of tumor cells required for engraftment.

PMID- 19582419
TI  - Identification of murine and human acute myeloid leukemia stem cells.
AB  - There is now compelling evidence to show that tumors, once believed to be a
      homogeneous mass of abnormally proliferative cells, comprise a heterogeneous
      population of transformed cells resembling the hierarchically organized
      populations in the corresponding tissue. At the top of this tumor hierarchy are
      the cancer stem cells (CSCs) which are critical for tumor growth and maintenance
      as they constantly replenish the tumor bulk and are believed to be resistant to
      most conventional chemotherapies. The first evidence for both malignant hierarchy
      and CSCs came from studies on acute myeloid leukemia (AML) followed by mounting
      evidence in other types of cancer. Murine models of leukemia have been the
      proving ground for the elucidation of key novel concepts in this nascent field of
      CSC research. A spate of recent studies highlighting the importance of CSCs in
      cancer has accentuated the need for identifying and characterizing these cells.
      The frequency of CSCs in the leukemic bulk (LSCs) is usually estimated by in vivo
      limiting-dilution transplantation assays of leukemic cells into recipient animal
      hosts in which identical leukemias can be regenerated. Each cell that is capable
      of propagating the leukemia in secondary recipients is termed a leukemia
      propagating cell (LPC). LSC candidates have been typically identified by the
      systematic dissection of compartments within a heterogeneous tumor to determine
      the subpopulation which shows maximal enrichment for LPCs. This is performed by
      determining the frequency of LPCs in each of those purified subpopulations, as
      has been described in both human and murine models of leukemia. It is important
      to mention that even though leukemia repopulation is often used as a surrogate
      for LSC estimation, the term LPCs can be equated with LSCs only if the phenotypic
      heterogeneity of the original tumor mass is regenerated upon tumor propagation
      into secondary recipients. The first part of the chapter deals with the
      estimation of LPCs in syngenic or congenic murine-murine models. In the second
      part, murine xenograft models for the estimation of LSCs in human leukemias are
      described.

PMID- 19582420
TI  - Methods for analysis of brain tumor stem cell and neural stem cell self-renewal.
AB  - Neural stem cells (NSC) self-renew and are multipotent, producing neurons and
      glia. Recent studies have shown that brain tumors (BT) contain cells that, like
      NSC, self-renew and are multipotent, producing the different types of cells found
      within the brain tumors. These brain tumor stem cells are a kind of cancer stem
      cell, competent to form tumors that mimic the parent tumor in experimental
      animals. Studies from our laboratory and others have demonstrated that brain
      tumor stem cells and NSC share similar mechanisms and pathways for proliferation.
      For example, we have identified that one of the AMPK/snf1 kinases, maternal
      embryonic leucine zipper kinase (MELK), is highly expressed in NSC and malignant
      brain tumors, as well as in brain tumor stem cell-enriched cell cultures.
      Analysis of transgenic MELK-reporter mice indicated that MELK is expressed in NSC
      in vivo, and our in vitro studies demonstrated that MELK is required for NSC self
      renewal. We have also found that MELK is required for proliferation of putative
      BT stem cells. Utilizing our studies with MELK as an example, this chapter
      describes methods to culture NSC and BT stem cells, and to analyze the pathways,
      which regulate self-renewal of those cells.

PMID- 19582421
TI  - Prospective identification of cancer stem cells with the surface antigen CD133.
AB  - Cancer cells do not share equal tumor-initiating potential. Only cancer stem
      cells (CSCs) can initiate cancer, which is important clinically because they
      should be eradicated to treat cancer patients. The purpose of experimental
      methods for identification of CSC is to isolate CSCs among various kinds of
      cancer cells in cancer masses. To identify CSCs, cancer masses derived from
      patients should be dissociated into single cells. Dissociated cells are
      classified into several groups according to expression status of one or several
      surface proteins using magnetic cell sorting (MACS) or fluorescence-activated
      cell sorting (FACS) methods. Sorted cells are cultured in a specialized culture
      medium for stem cells or inoculated into the primary cancer site of
      immunodeficient mice. In this chapter detailed experimental methods will be
      described and glioblastoma will be used as an example of solid cancers.

PMID- 19582423
TI  - Methodologies in assaying prostate cancer stem cells.
AB  - The cancer stem cell (CSC) theory posits that only a small population of tumor
      cells within the tumor has the ability to reinitiate tumor development and is
      responsible for tumor homeostasis and progression. Tumor initiation is a defining
      property of putative CSCs, which have been reported in both blood malignancies
      and solid tumors. In order to test whether any given human tumor cell population
      has CSC properties, the relatively enriched single cells have to be put into a
      foreign microenvironment in a recipient animal to test their tumorigenic
      potential. Furthermore, various in vitro assays need be performed to demonstrate
      that the presumed CSCs have certain biological properties normally associated
      with the stem cells (SCs). Herein, we present a comprehensive review of the
      experimental methodologies that our lab has been using in assaying putative
      prostate cancer (PCa) SCs in culture, xenograft tumors, and primary tumor
      samples.

PMID- 19582422
TI  - Neurosphere culture and human organotypic model to evaluate brain tumor stem
      cells.
AB  - The brain tumor stem cell (BTSC) hypothesis is based on the premise that there is
      a subpopulation of cells within tumors with tumorigenic and pluripotent
      properties. BTSC are believed to be responsible for both the initiation of brain
      tumors and their resistance to current therapeutic modalities. This new paradigm
      stresses the need for adequate techniques to culture and characterize this
      special population of cells. Furthermore, the use of different cell migration
      assays offers the possibility to evaluate the processes involved in glioma
      metastasis. In this chapter, we summarize a method to culture, analyze the
      cellular characteristics, and study the invasion of BTSCs using a neurosphere
      assay, cryostat sectioning, and human organotypic brain cortex migration assay,
      respectively.

PMID- 19582424
TI  - Characterization of nonmalignant and malignant prostatic stem/progenitor cells by
      Hoechst side population method.
AB  - Recent technical progress in the field of cancer stem/progenitor cell research
      revealed that these malignant cells may provide critical roles for primary tumor
      growth, metastases at distant tissues and organs, treatment resistance, and
      disease relapse. The precise molecular oncogenic events that frequently occur in
      cancer stem/progenitor cells and their early progenies during the early and late
      stages of cancer progression as well as their contribution to the treatment
      resistance and disease recurrence remain poorly defined. This lack of information
      on the deregulated gene products that may be involved in the malignant
      transformation of tissue-resident adult stem/progenitor cells into highly
      tumorigenic and/or migrating cancer stem/progenitor cells emphasizes the urgent
      need to perform future investigations. Toward this direction, we describe in this
      book chapter the characterization of nonmalignant and malignant prostatic
      stem/progenitor cells from well-established cell lines by Hoechst side population
      method. This novel approach should help to establish novel in vitro and in vivo
      models of human cancer stem/progenitor cell mimicking more closely the genetic
      and phenotypic changes occurring during the different stages of prostate
      carcinogenesis and disease progression in clinical settings. Of therapeutic
      interest, the identification of new biomarkers and molecular targets specific to
      these prostatic cancer-initiating cells should also help to develop more
      effective diagnostic and prognostic tests and chemopreventive and therapeutic
      treatments for the patients diagnosed at early and late stages of disease
      progression.

PMID- 19582425
TI  - Anchorage-independent growth of prostate cancer stem cells.
AB  - Prostate cancer is a major health concern in the Western world. Prostate cancer
      stem cells have been implicated to be involved in, if not solely responsible for
      prostate cancer initiation and relapse after surgical, hormonal, and
      chemotherapy. Until now, the identity of the presumed prostate cancer stem cell
      has been illusive and the efforts to characterize such cells have been hampered
      by the lack of efficient prostate stem cell activity assay. Anchorage-independent
      growth of brain and mammary stem cells in vitro has been proved to be a useful
      tool to enrich and characterize neural and mammary stem cells. Recently, we have
      successfully established a prostosphere cultivation method employing strategies
      similar to neurosphere and mammosphere cultures. Our results demonstrate that
      prostosphere-forming cells possess stem cell characters and are significantly
      over-represented in cancer tissues.

PMID- 19582426
TI  - Identification of human pancreatic cancer stem cells.
AB  - Emerging evidence suggests that malignant tumors are composed of a small subset
      of distinct cancer cells, termed "cancer stem cells" (typically less than 5% of
      total cancer cells based on cell surface marker expression), which have great
      proliferative potential, as well as more differentiated cancer cells, which have
      very limited proliferative potential. Data have been provided to support the
      existence of cancer stem cells in several different types of cancer, including
      human blood, brain, prostate, ovarian, melanoma, colon, and breast cancers. We
      have recently reported the identification of a subpopulation of pancreatic cancer
      cells that express the cell surface markers CD44+CD24+ESA+ (0.2-0.8% of all human
      pancreatic cancer cells) that function as pancreatic cancer stem cells. The
      CD44+CD24+ESA+ pancreatic cancer cells are highly tumorigenic and possess the
      stem cell-like properties of self-renewal and the ability to produce
      differentiated progeny. Pancreatic cancer stem cells also demonstrate
      upregulation of molecules important in developmental signaling pathways,
      including sonic hedgehog and the polycomb gene family member Bmi-1. Of clinical
      importance, cancer stem cells in several tumor types have shown resistance to
      standard therapies and may play a role in treatment failure or disease
      recurrence. Identification of pancreatic cancer stem cells and further
      elucidation of the signaling pathways that regulate their growth and survival may
      provide novel therapeutic approaches to treat pancreatic cancer, which is
      notoriously resistant to standard chemotherapy and radiation.

PMID- 19582427
TI  - Cancer stem cells in head and neck squamous cell carcinoma.
AB  - The cancer stem cell hypothesis states that within a tumor only a subset of
      cells, the "cancer stem cells" (CSC), are capable of initiating and propagating
      the disease. In various cancers such cells have been identified and prospectively
      isolated based on the presence of specific cell surface antigens. In head and
      neck squamous cell carcinomas, we have shown that the CSCs are contained within
      the CD44+ subset of tumor cells. This subset contains cells capable of initiating
      tumor growth in mice that recapitulates the original tumor heterogeneity.
      Furthermore, they have a primitive cellular morphology, express high levels of
      nuclear BMI1, and are arrayed in characteristic tumor microdomains. The methods
      used to purify this subset of tumorigenic cells, to characterize their gene
      expression profiles, and to identify their physical location within the context
      of the whole tumor are described here.

PMID- 19582428
TI  - Pituitary adenoma stem cells.
AB  - The identification of a subpopulation of brain tumor cells with potent
      tumorigenic capacity strengthens the cancer stem cell hypothesis of the origin of
      the tumors that has recently attracted the attention of many researchers. Reports
      have been published on the identification of tumor cells with stem cells
      characteristics in different types of tumors (acute myelogenic leukemia, breast
      cancer, prostate cancer, bone sarcomas, liver cancer, and melanomas). We and
      other groups have previously reported the isolation of cancer stem cells from
      adult glioblastoma multiforme. These cells express stem cell markers, and when
      differentiated they express glial and neuronal markers. In vivo they give a tumor
      that recapitulates the characteristics of the tumor in the patient. More recently
      we have isolated tumor stem-like cells also from benign tumors like pituitary
      adenomas. Cells derived from pituitary adenomas are able to grow as floating
      aggregates resembling the neurospheres (typical of normal stem cells) in a medium
      supplemented by growth factors (EGF and bFGF). The immunocytochemical analysis
      revealed that pituitary tumor stem-like cells are positives for nestin and, when
      grown for ten days in differentiation medium they express GFAP, BIII tubulin, and
      S-100. In vitro tumor stem-like cells derived from a patient with a somatotroph
      adenoma showed high production of growth hormone and prolactin, while cells
      derived from the same patient but grown in presence of fetal bovine serum showed
      no production of hormones.

PMID- 19582429
TI  - Genome-wide DNA methylation profiling: the mDIP-chip technology.
AB  - Aberrant DNA methylation is one of the major characteristics of tumor cells in
      addition to genetic and other epigenetic alterations. Evidence shows that both
      regional hypermethylation and global hypomethylation can occur in cancer cells.
      Increased DNA methylation can be found at select tumor-suppressor gene promoters,
      causing the silencing of these genes in tumorigenic cells. At the same time, a
      global decrease in DNA methylation is frequently observed in cancer cells, which
      may contribute to genome instability. Unlike genetic mutations, hypermethylation
      at tumor-suppressor gene promoters can be reversed with epigenetic therapy by
      using DNA demethylating agents.To better understand the mechanisms of cancer
      initiation and progression, and to better assess the effects of epigenetic
      therapy, a reliable high-throughput method for genome-wide DNA methylation
      analysis is needed. Recently, the process of coupling methylated DNA
      immunoprecipitation (mDIP) with microarray hybridization has been proven to be a
      successful strategy to map genome-wide DNA methylation patterns in different cell
      types.

PMID- 19582430
TI  - The contribution of niche-derived factors to the regulation of cancer cells.
AB  - In normal adult tissues, paracrine signals that derive from the stem cell niche,
      or microenvironment, play an important role in regulating the critical balance
      between activity and quiescence of stem cells. Similarly, evidence has emerged to
      support the hypothesis that signals derived from the microenvironment regulate
      cancer cells in an analogous manner. We recently reported that in basal cell
      carcinoma of the skin and in diverse other solid tumors, fibroblasts that
      comprise the tumor cell niche are, indeed, molecularly distinct from those that
      comprise the normal stroma. In particular, we found evidence suggesting that
      expression of secreted BMP antagonists by tumor-associated stromal cells may
      promote self-renewal of tumor stem cells in vivo. This chapter describes methods
      for identifying and evaluating the molecular signals that derive from fibroblasts
      in human tumors.

PMID- 19582431
TI  - Dendritic cell vaccines for cancer stem cells.
AB  - Accumulating evidence suggests that only a fraction of neoplastic cells, defined
      as cancer stem cells (CSC), are responsible for tumor perpetuation. Recent data
      suggest that neurospheres (NS) from glioblastoma multiforme (GBM) are enriched in
      CSC. The characterization of this subpopulation of brain tumor cells with a
      potent tumorigenic activity supports the cancer stem cell hypothesis in solid
      tumors and may imply that cancer cells are differentially targeted by treatments,
      including dendritic cell (DC) immunotherapy. To test therapeutic strategies, a
      good model mimicking the characteristics of GBM-NS and GBM-AC (Adherent Cells)
      was necessary. One of the most frequently used murine brain tumor models is the
      GL261 glioma cell line. To see whether GL261 cells could mimic the growth of
      human GBM-CSC we let them grow in EGF/bFGF without serum. After 5 days
      neurospheres were visible in the culture medium and were proliferating
      continuously. The characterization in vivo and in vitro demonstrates that GL261
      NS satisfy criteria used to identify CSC and are more immunogenic than AC. DC
      loaded with GL261-NS lysates protect mice against tumors from both GL261-NS and
      GL261-AC. Our results suggest that only DC vaccination against neurospheres can
      restrain the growth of a highly infiltrating and aggressive model of glioma and
      may have implications for the design of novel, more effective immunotherapy
      trials for malignant glioma and possibly other malignancies.

PMID- 19582432
TI  - Maintaining and engineering neural stem cells for delivery of genetically encoded
      therapy to brain tumors.
AB  - Despite advances for the treatment of cancer, the prognosis for patients
      suffering from malignant brain tumors remains dismal. High-grade neoplasms, such
      as gliomas, are highly invasive and spawn widely disseminated microsatellites
      that have limited the efficacy of surgical and adjunctive therapies. The cancer
      stem cell hypothesis suggests that conventional chemotherapeutic treatments kill
      differentiated and differentiating cells which often form the bulk of the tumor.
      One major concern is that the cells which give rise to the tumor, the cancer stem
      cells, remain untouched and may be responsible for a relapse of the disease.
      Therefore, an adjunctive therapy to current cancer treatment is critical for the
      survivability of patients suffering from brain tumors. We have successfully
      engineered tumor-tropic neural stem cells to deliver antineoplastic gene products
      directly to the tumor-producing cells. This potential therapeutic strategy may
      safely eradicate tumor-producing cells in the brain while minimizing damage to
      normal, healthy cells.

PMID- 19582433
TI  - Measurement of multiple drug resistance transporter activity in putative cancer
      stem/progenitor cells.
AB  - Multiple drug resistance, mediated by the expression and activity of ABC
      transporters, is a major obstacle to antineoplastic therapy. Normal tissue stem
      cells and their malignant counterparts share MDR transporter activity as a major
      mechanism of self-protection. Although MDR activity is upregulated in response to
      substrate chemotherapeutic agents, it is also constitutively expressed on both
      normal tissue stem cells and a subset of tumor cells prior to the initiation of
      therapy, representing a built-in obstacle to therapeutic ratio. Constitutive and
      induced MDR activity can be detected in cellular subsets of disaggregated
      tissues, using the fluorescent substrates Rhodamine 123 and Hoechst 33342 for
      ABCB1 (also known as P-gp and MDR1) and ABCG2 (BCRP1). In this chapter, we will
      describe the complete procedure for the detection of MDR activity, including: (1)
      Preparing single-cell suspensions from tumor and normal tissue specimens; (2) An
      efficient method to perform cell surface marker staining on large numbers of
      cells; (3) Flow cytometer setup and controls; (4) Simultaneous measurement of
      Hoechst 33342 and Rhodamine123 transport; and (5) Data acquisition and analysis.

PMID- 19582434
TI  - Estimation of human maximum tolerable intake  for methylmercury based on two
      recent studies in monkeys.
AB  - Results of long-term toxicity studies of methylmercury (MeHg) in monkeys have
      been reported. The aim of this study was to estimate the threshold body burden,
      blood level and threshold daily intake (TDI) of MeHg for monkey and human. The
      concepts of this study stood on that body burden of MeHg would follow the
      accumulation theory, and that the more intake of MeHg, the earlier the
      neurotoxicity appeared, vice versa. The threshold blood level (TBL) of monkey was
      estimated to be 0.71 as Hg mg/L and the body burden was estimated to be 4.83 as
      Hg mg/kg. The TDI was estimated to be 0.025 as Hg mg/kg day. In human, the TBL
      was estimated with compensation by elimination constants of human and monkey. The
      blood threshold limit and TDI of human were estimated to be 0.33 as Hg mg/L and
      0.0046 as Hg mg/kg day, respectively. The estimated body burden was 0.46 as Hg
      mg/kg.

PMID- 19582436
TI  - Material ejection and redeposition following atmospheric pressure near-field
      laser ablation on molecular solids.
AB  - Near-field laser ablation (NF-LA) coupled with mass spectrometry (MS) is very
      promising for highly spatially resolved chemical analyses on various substrates
      at atmospheric pressure, for example, in materials and life science applications.
      Although nanoscale sample craters can be produced routinely, no molecular mass
      spectra of ablated material from craters of <or=1 microm diameter have ever been
      acquired by NF-LA MS at atmospheric pressure. Some of the pressing questions are
      thus how much of the ablated material is transported into the mass spectrometer
      and in what form. Therefore, material redeposition on the near-field tip's
      surface from laser ablation of molecular solids was characterized with scanning
      electron microscopy. The crater profiles were studied by scanning probe
      microscopy. The results shown in this study demonstrate that there could be as
      much as 70% of the ablated material deposited on the near-field tip's surface.
      The redeposited products were found to be confined to a height of approximately
      50 microm, thus suggesting that most components inside near-field ablation plumes
      propagate about the same distance for both anthracene and tris(8
      hydroxyquinolinato)aluminum. Nanoparticles ablated from craters of <or=1 microm
      diameter are clearly observed. Furthermore, observation of tips after ablation of
      an anthracene surface angled at 60 degrees with respect to a horizontal surface
      shows that the direction of the near-field ablation plume is neither in the
      direction of the surface normal nor towards the axis of incident laser beam but
      deflected further away from surface normal.

PMID- 19582435
TI  - The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile
      mechanism characteristic of the mouse ileum.
AB  - We explored whether the M(2) muscarinic receptor in the guinea pig ileum elicits
      a highly potent, direct-contractile response, like that from the M(3) muscarinic
      receptor knockout mouse. First, we characterized the irreversible receptor
      blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout
      mice to verify its M(3) selectivity. Then, we used 4-DAMP mustard to inactivate
      M(3) responses in the guinea pig ileum to attempt to reveal direct, M(2) receptor
      mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent
      contractions in ileum from wild-type, M(2) receptor knockout, and M(3) receptor
      knockout mice characterized by negative log EC(50) (pEC (50)) values +/- SEM of
      6.75 +/- 0.03, 6.26 +/- 0.05, and 6.99 +/- 0.08, respectively. The corresponding
      E (max) values in wild-type and M(2) receptor knockout mice were approximately
      the same, but that in the M(3) receptor knockout mouse was only 36% of wild type.
      Following 4-DAMP mustard treatment, the concentration-response curve of
      oxotremorine-M in wild-type ileum resembled that of the M(3) knockout mouse in
      terms of its pEC (50), E (max), and inhibition by selective muscarinic
      antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M(3) responses
      selectively and renders the muscarinic contractile behavior of the wild-type
      ileum similar to that of the M(3) knockout mouse. Following 4-DAMP mustard
      treatment, the contractile response of the guinea pig ileum to oxotremorine-M
      exhibited low potency and a competitive-antagonism profile consistent with an
      M(3) response. The guinea pig ileum, therefore, lacks a direct, highly potent,
      M(2)-contractile component but may have a direct, lower potency M(2) component.

PMID- 19582437
TI  - Frequency-dependent modulation of muscle sympathetic nerve activity by sinusoidal
      galvanic vestibular stimulation in human subjects.
AB  - We have previously demonstrated that selective modulation of vestibular inputs,
      via sinusoidal galvanic vestibular stimulation (GVS) delivered at 0.5-0.8 Hz, can
      cause partial entrainment of muscle sympathetic nerve activity (MSNA). Given that
      we had seen interaction between the dynamic vestibular input and the normal
      cardiac-locked MSNA rhythm, we tested the hypothesis that frequencies of GVS
      remote from the cardiac frequency would cause a greater modulation of MSNA than
      those around the cardiac frequency. Bipolar binaural sinusoidal GVS (+/-2 mA, 200
      cycles) was applied to the mastoid processes in 11 seated subjects at frequencies
      of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 and 2.0 Hz. In all subjects, the stimulation
      evoked robust vestibular illusions of "rocking in a boat" or "swinging from side
      to side." Cross-correlation analysis revealed a cyclic modulation of MSNA at all
      frequencies, with the modulation index being similar between 1.1 Hz (78.5 +/-
      3.7%) and 2.0 Hz (77.0 +/- 4.3%). However, vestibular modulation of MSNA was
      significantly stronger at 0.2 Hz (93.1 +/- 1.7%) and significantly weaker at 0.8
      Hz (67.2 +/- 1.8%). The former suggests that low-frequency changes in vestibular
      input, such as those associated with postural changes, preferentially modulate
      MSNA; the latter suggests that vestibular inputs compete with the stronger
      baroreceptor inputs operating at the cardiac rhythm (approximately 0.8 Hz), with
      vestibular modulation of MSNA being greater when this competition with the
      baroreceptors is reduced.

PMID- 19582438
TI  - The effects of constraining eye movements on visually evoked steering responses
      during walking in a virtual environment.
AB  - We have previously shown that participants who step in place while viewing a
      moving scene that simulates walking towards and turning a corner demonstrate
      anticipatory sequential reorientation of axial body segments with timing
      characteristics similar to those seen during real turning. We propose that the
      coordination of axial body segments during steering represents a robust pre
      programmed postural synergy triggered by gaze realignment in the desired
      direction of travel. The primary aim of the current study was to test this
      hypothesis by studying the effects of constraining eye movement on visually
      evoked steering responses exhibited by participants stepping in place in a
      virtual environment. We predicted that preventing participants from generating
      anticipatory gaze shifts would significantly attenuate or eliminate visually
      evoked postural responses. A secondary aim was to investigate the nature of the
      visual cues that trigger the coordinated eye and whole body response by testing
      whether spatial (distance from the corner) or temporal (time to contact with
      corner) parameters modulated with the speed of the visual scene (normal, half
      speed and double speed). Six university graduate student (27.8 +/- 5.0 years)
      participants were asked to step in place at a self-selected comfortable pace
      while immersed in a virtual environment which simulated walking down a hallway
      and turning a corner. In half of the trials participants were required to
      maintain gaze direction on a static target placed in the middle of the viewing
      screen. Whole body kinematics and gaze behaviour were recorded. In support of our
      hypothesis, gaze fixation on a stationary target resulted in the suppression of
      anticipatory steering responses. Although postural adjustments were still
      observed during constrained gaze trials, they were reactive rather than
      anticipatory in nature and were significantly smaller than trials in which gaze
      was unconstrained. Our results further suggest that the time of eye and body
      reorientation is dependent on the temporal rather than spatial visual cues, i.e.
      visually specified estimation time to contact with the virtual corner. These
      results indicate that gaze redirection is a prerequisite for the initiation of a
      pre-programmed steering synergy and suggest that these robust postural responses
      are intimately linked to the oculomotor control processes within the central
      nervous system.

PMID- 19582439
TI  - Individualized dosing of aminoglycosides in neonates: mission accomplished or
      work in progress?

PMID- 19582441
TI  - 'Molar tooth' sign in Joubert syndrome.

PMID- 19582440
TI  - Influence of clinical and genetic factors on warfarin dose requirements among
      Japanese patients.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of clinical and
      genetic factors on warfarin dose requirements in the Japanese population.
      METHODS: We enrolled 125 patients on stable warfarin anticoagulant therapy with
      an international normalized ratio maintained between 1.5 and 3.0. PCR-based
      methods were performed to analyze genetic polymorphisms in the genes
      pharmacokinetically and pharmacodynamically related to warfarin reactions,
      including cytochrome P450 (CYP) 2C9, vitamin K epoxide reductase complex subunit
      1 (VKORC1), gamma-glutamyl carboxylase (GGCX) and factor VII (FVII). RESULTS: The
      presence of CYP2C9*3 and VKORC1-1639G>A had a significant impact on the mean
      maintenance dose of warfarin (CYP2C9*1/*1 2.74 +/- 1.24 mg/day vs. *1/*3 and
      *3/*3 1.56 +/- 0.85 mg/day, P = 0.009; VKORC1-1639AA 2.42 +/- 0.95 mg/day vs. GA
      3.71 +/- 1.43 mg/day vs. GG 7.25 +/- 0.35 mg/day, P < 0.001). In the multiple
      linear regression model, the combination of age, body surface area, and genotypes
      of CYP2C9*3 and VKORC1-1639G>A explained 54.8% of the variance in warfarin dose
      requirements. CONCLUSIONS: The influences of CYP2C9*3 and VKORC1-1639G>A on the
      maintenance dose of warfarin were well-defined in Japanese patients, while
      polymorphisms of GGCX and FVII did not affect it. The model established in this
      study might provide us most likely individual maintenance dose based on clinical
      and genetic backgrounds.

PMID- 19582442
TI  - Dentigerous cyst associated with a displaced tooth in the maxillary sinus: an
      unusual cause of recurrent sinusitis in an adolescent.
AB  - We report an unusual case of a displaced maxillary molar and associated
      dentigerous cyst within the maxillary sinus in an adolescent presenting as
      recurrent sinusitis. Although a rare cause of sinusitis in children, dentigerous
      cysts should be included in the differential diagnosis for causes of persistent
      or recurrent sinusitis in this age group. This report provides further evidence
      for obtaining imaging studies when managing pediatric sinusitis that does not
      respond to standard antibiotic therapy. We discuss management options for these
      lesions including the differential diagnoses and need for follow-up.

PMID- 19582443
TI  - Delayed, life-threatening lower gastrointestinal hemorrhage in an infant after
      serial transverse enteroplasty: treatment with transcatheter n-butyl-2
      cyanoacrylate embolization.
AB  - We report a case of n-butyl-2-cyanoacrylate glue embolization of life-threatening
      lower gastrointestinal (LGI) hemorrhage in a 10-month-old boy. The child had a
      history of gastroschisis and short-bowel syndrome. Six months prior to the LGI
      bleed, he had undergone a serial transverse enteroplasty (STEP) to lengthen his
      intestine. To the best of our knowledge this is both the first report of
      successful glue embolization for LGI bleeding in a child and also the first
      report of severe hemorrhage after the STEP procedure.

PMID- 19582445
TI  - Ca2+ spiral waves in a spatially discrete and random medium.
AB  - It is well known that the spatial distribution of the calcium ion channels in the
      endoplasmic reticulum is discrete. We study the Ca(2+) spiral pattern formation
      based on a model in which ion channels are discretely and randomly distributed.
      Numerical simulations are performed on different types of media with the Ca(2+)
      release sites uniformly distributed, discretely and uniformly arranged, or
      discretely and randomly arranged. The comparisons among the different media show
      that random distribution is necessary for spontaneous initiation of Ca(2+) spiral
      waves, and the discrete and random distribution is of significance for spiral
      waves under physiologically reasonable conditions. The period and velocity of
      spiral waves are also calculated, and they are not prominently changed by varying
      the type of medium.

PMID- 19582446
TI  - Production of a cytotoxic cationic antibacterial peptide in Escherichia coli
      using SUMO fusion partner.
AB  - Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad
      spectrum activities against bacteria, fungi, and tumor cells, which may possibly
      be used as an antimicrobial agent. We report here the application of small
      ubiquitin-related modifier (SUMO) fusion technology to the expression and
      purification of cationic antibacterial peptide ABP-CM4. The fusion protein
      expressed in a soluble form was purified to a purity of 90% by Ni-IDA
      chromatography and 112 mg protein of interest was obtained per liter of
      fermentation culture. After the SUMO-CM4 fusion protein was cleaved by the SUMO
      protease at 30 degrees C for 1 h, the cleaved sample was re-applied to a Ni-IDA.
      Finally, about 24 mg recombinant CM4 was obtained from 1 l fermentation culture
      with no less than 96% purity and the recombinant CM4 had similar antimicrobial
      properties to the synthetic CM4. Thus, the SUMO-mediated peptide expression and
      purification system potentially could be employed for the production of
      recombinant cytotoxic peptides.

PMID- 19582447
TI  - Microbiological production of tocopherols: current state and prospects.
AB  - Tocopherols are antioxidants that prevent various diseases caused by oxidative
      stress. Tocochromanols comprise four isoforms of tocopherols and four isoforms of
      tocotrienols but alpha-tocopherol is the most abundant and active isoform in
      human and animal tissues. Tocopherols are used as dietary supplements for human,
      as food preservatives, in manufacture of cosmetics, and for fortification of
      animal feed. Only photosynthetic cells are known to accumulate detectable
      concentrations of tocopherols. Tocopherols can be extracted and purified or
      concentrated from vegetable oils and other higher plant materials. However, the
      concentrations in these higher plant materials are very low and there are high
      proportions of the less-active homologues of tocopherols. Among the many strains
      of photosynthetic microorganisms known to accumulate tocopherols, Euglena
      gracilis is promising for commercial production of alpha-tocopherol. The growth
      rate and alpha-tocopherol contents are relatively high and alpha-tocopherol
      comprise more than 97% of all the tocopherols accumulated by Euglena gracilis.
      Although a lot of work has been done to increase the contents and composition of
      tocopherols in higher plants through genetic and metabolic engineering, work on
      genetic modification of microorganisms for increased tocopherol accumulation is
      scarce. Many cultivation systems have been investigated for efficient production
      of tocopherol by Euglena gracilis. However, those that involve heterotrophic
      metabolism are more promising. Bubble columns and flat-plate photobioreactors are
      more suitable for commercial production of tocopherols, than the tubular,
      internally illuminated, and open-air photobioreactors.

PMID- 19582448
TI  - Biosynthesis of novel terpolymers poly(lactate-co-3-hydroxybutyrate-co-3
      hydroxyvalerate)s in lactate-overproducing mutant Escherichia coli JW0885 by
      feeding propionate as a precursor of 3-hydroxyvalerate.
AB  - Novel lactate (LA)-based terpolymers, P[LA-co-3-hydroxybutyrate(3HB)-co-3
      hydroxyvalerate(3HV)]s (PLBVs), were produced in LA-overproducing mutant,
      Escherichia coli JW0885, which was found to be a superior host for the efficient
      production of LA-based polyesters. Recombinant E. coli JW0885 harboring the genes
      encoding LA-polymerizing enzyme (Ser325Thr/Gln481Lys mutant of
      polyhydroxyalkanoate synthase from Pseudomonas sp. 61-3) and three monomer
      supplying enzymes [propionyl-CoA transferase, beta-ketothiolase, and nicotinamide
      adenine dinucleotide phosphate (reduced form) (NADPH)-dependent acetoacetyl-CoA
      reductase] was aerobically grown on glucose with feeding of propionate as a
      precursor of 3-hydroxyvaleryl-CoA (3HV-CoA). Gas chromatography and nuclear
      magnetic resonance (NMR) analyses revealed that polymers accumulated in the cells
      were composed of LA, 3HB, and 3HV units, thus being identified as terpolymers,
      PLBVs. In addition, (1)H-NMR analysis suggested the existence of LA-3HV sequence
      in the terpolymer. When 100 mg/l of sodium propionate was added into the medium,
      3HV fraction in the terpolymer linearly reached up to 7.2 mol%, while LA fraction
      was inversely decreased. This phenomenon could be due to the change in metabolic
      fluxes of lactyl-CoA (LA-CoA) and 3HV-CoA depending on the concentration of
      propionate fed into the medium.

PMID- 19582449
TI  - Central giant cell granuloma of the jaws: clinical and radiological evaluation of
      22 cases.
AB  - OBJECTIVE: The objective was to investigate the clinical and radiological
      characteristics of central giant cell granulomas (CGCGs) of the jaws. METHODS: A
      retrospective analysis of a 20-year database was performed regarding both
      clinical and radiological features of 22 patients affected with CGCGs of the
      jaws. RESULTS: Fourteen women and 8 men were included with the age range of 7-81
      years (mean 31.7 years). Among the 22 lesions, 16 were located in the mandible
      and 6 in the maxilla. Painless swelling was the most common clinical feature in
      18 of all cases. Limited mouth opening was noted in 2 patients where the lesions
      involved the condyle. Radiographically, 13 lesions were homogeneously osteolytic
      and 9 lesions were trabeculated. Fifteen lesions were unilocular and 14 lesions
      presented with well-defined but not sclerotic margins. CT images in 5 patients
      clearly showed the trabeculation within the lesions. The follow-up ranged from
      1.5 to 11 years with a mean period of 5 years. Three out of 9 aggressive and 1
      out of 13 nonaggressive lesions developed recurrence. CONCLUSIONS: Diagnosis of
      CGCGs of the jaws depends on both correct interpretation of clinical,
      radiographic and pathological data. Differentiation between aggressive and
      nonaggressive CGCGs should be considered to improve individual treatment
      planning.

PMID- 19582450
TI  - Predictive potential of pre-operative functional neuroimaging in patients treated
      with subthalamic stimulation.
AB  - PURPOSE: The aim of this study was to investigate the predictive potential of pre
      operative regional cerebral blood flow (rCBF) in the pre-supplementary motor area
      (pre-SMA) and clinical factors in Parkinson's disease (PD) patients treated with
      subthalamic nucleus (STN) stimulation. METHODS: Ten patients underwent rCBF SPECT
      and motor Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post
      operatively during stimulation at 5 and 42 months. Statistical parametric mapping
      (SPM) was used to extract rCBF values in the pre-SMA because it is related with
      motor improvement. Post-operative outcomes included motor response to stimulation
      and percent improvement in UPDRS. Pre-operative predictors were explored by
      correlation test, linear regression and multivariate analyses. RESULTS: Higher
      pre-operative rCBF in the pre-SMA and younger age were associated with favourable
      outcomes at 5 and 42 months. Pre-operative rCBF results were significantly
      associated with baseline clinical factors. CONCLUSION: This study shows that PD
      patients with younger age have higher rCBF values in the pre-SMA and better
      outcome, thus giving the rationale to the hypothesis that STN stimulation could
      be considered early in the course of disease.

PMID- 19582451
TI  - Routine patellar resurfacing using an inset patellar technique.
AB  - The management of the patella in total knee arthroplasty still causes
      controversy. Whether or not to resurface the patella in primary total knee
      arthroplasty remains unclear. In this study we examined 220 consecutive total
      knee replacements, by a single surgeon, where the patella was routinely
      resurfaced using the inset technique. All patellae were suitable for resurfacing.
      Patellar thickness was not altered in 54.5% of patellae. In 97.2% the patella was
      within 2 mm of the original thickness. There were no significant complications.
      In this study we have found that the inset technique of patella resurfacing in
      total knee replacement is a simple and safe resurfacing procedure.

PMID- 19582452
TI  - Increased risk of recurrent thrombosis in patients with essential thrombocythemia
      carrying the homozygous JAK2 V617F mutation.
AB  - Evidence suggests that the JAK2 V617F mutation is associated with an increased
      risk of first thrombosis in patients with essential thrombocythemia (ET). Whether
      this mutation is also a risk factor for recurrent thrombosis is currently
      unknown. To investigate the impact of the JAK2 V617F mutation on the risk of
      recurrent thrombosis in patients with ET, we carried out a multicentre
      retrospective cohort study. We recruited 143 patients with previous arterial
      (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%)
      carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall,
      after adjustment for sex, age, presence of vascular risk factors, and treatment
      after the first thrombosis, the presence of the JAK2 mutation did not predict
      recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the
      individuals homozygous for the JAK2 V617F (allele burden >50%) mutation had an
      increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95%
      CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent
      risk factor for recurrent thrombosis in patients with ET.

PMID- 19582453
TI  - A case of generalized MALT lymphoma with IgM paraproteinemia and peripheral blood
      involvement.

PMID- 19582454
TI  - Reversible posterior leukoencephalopathy syndrome following R-CHOP therapy for
      diffuse large B-cell lymphoma.

PMID- 19582455
TI  - Serum cytokines in follicular lymphoma. Correlation of TGF-beta and VEGF with
      survival.
AB  - The prognosis of follicular lymphoma could vary with the tumor immune
      microenvironment. We evaluated the prognostic value of serum levels of ten
      cytokines. Our study cohort included 60 follicular lymphoma patients and 20
      controls. Serum was available at diagnosis in 31 patients, at first relapse in
      18, and complete remission in 11. Bioplex technology was used for determination
      of nine cytokines [interleukin (IL)-1Ra, IL-6, IL-7, IL-10, IL-13, tumor necrosis
      factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF), platelet
      derived growth factor (PDGF), and basic fibroblast growth factor (b-FGF)].
      Transforming growth factor beta (TGF-beta) was measured by sandwich enzyme-linked
      immunosorbent assay. IL-1Ra, IL-6, IL-7, IL-10, IL-13, TNF-alpha, VEGF, and PDGF
      levels were found increased in follicular lymphoma patients compared to controls.
      Multivariate analysis identified early stage and high TGF-beta levels as
      independent predictors of overall survival associated with improved outcome. High
      lactate dehydrogenase and VEGF levels were independently associated with poorer
      progression-free survival. These results show the prognostic value of TGF-beta
      and VEGF in follicular lymphoma and suggest their contribution to tumor
      microenvironment alterations.

PMID- 19582457
TI  - Severe neck and back pain in adolescence: remember osteoblastoma.
AB  - Osteoblastoma is a rare benign tumor of the bone. A 15-year-old boy presented
      with severe neck and back pain and was followed up for myofascial pain syndrome
      for 12 months. There was no neurologic deficit or scoliosis. The X-ray of the
      patient was normal. MRI revealed local destructive tumorous lesion of the T3-T5
      vertebrae. The tumor was resected by a spinal surgeon and histologic examination
      revealed osteoblastoma. The patient's complaints have been completely resolved
      and there was no recurrence during the follow-up.

PMID- 19582456
TI  - The -383A>C TNFRI polymorphism is associated with soluble levels and clinical
      activity in rheumatoid arthritis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a central role in inflammation, and
      it has been directly implicated in the pathogenesis of rheumatoid arthritis (RA).
      TNF-alpha activity is mediated through TNFRI and TNFRII cell surface receptors,
      which act as physiological attenuators of TNF-alpha activity. We recruited 190 RA
      patients and 190 healthy subjects (HS) in order to associate the -383A>C TNFRI
      polymorphism with sTNFRI levels and DAS28 score in RA. In results, sTNFRI levels
      were higher in RA patients than HS (P = 0.04). The -383A>C TNFRI polymorphism did
      not show significant differences in both studied groups. However, in the RA group
      the sTNFRI levels were significantly elevated (P = 0.004) in A/A genotype
      carriers. In addition, the A/A genotype carriers had the higher DAS28 score than
      A/C genotype (P = 0.02). These data suggest that -383A>C TNFRI polymorphism is
      not a susceptibility marker in RA, whereas the increased levels of sTNFRI could
      reflect the clinical activity in RA patients.

PMID- 19582458
TI  - Oligo-secretory myeloma in a patient with ankylosing spondylitis.
AB  - Non-secretory myeloma is a plasma cell dyscrasia characterized by the absence of
      serum and urinary monoclonal immunoglobulins on electrophoretic tests. Because of
      the lack of monoclonal protein, the identification of the disease is more
      difficult than for secretory myelomas. The coexistence of ankylosing spondylitis
      and multiple myeloma has been reported occasionally. We report a rare case of
      oligo-secretory myeloma coexistent with ankylosing spondylitis.

PMID- 19582459
TI  - Annual costs of rheumatoid arthritis in Turkey.
AB  - Objective of the present study is aimed to determine costs of rheumatoid
      arthritis (RA) based on reimbursement agencies perspective [Social Security
      Institution (SSI)] in Turkey. The international clinical guidelines for RA are
      followed for analysing the direct costs. Data were collected from hospital bills,
      social security institution price lists, and Ministry of Health drug price list.
      Direct costs of RA patients were estimated as euro 2,669.14 patient/year.
      Outpatient costs were found to be euro 240.40. Routine tests during the year were
      calculated as euro 98.85. Ten percent of patients are hospitalized per year, and
      0.62% of these patients received arthroplasty and/or other interventions. The
      cost during hospital stay was euro 87.76. euro 2,238 was determined as being paid
      per year for medication alone (including anti-TNF) and euro 4 is spent on
      auxiliary materials annually. Our data show a remarkable economic impact of RA
      over society. We hope that the cost of RA studies will help package price
      practices for reimbursement agencies.

PMID- 19582460
TI  - Efficacy of tacrolimus against Churg-Strauss syndrome in a patient with
      myasthenia gravis.

PMID- 19582461
TI  - Vanished humeral head in a patient with rheumatoid arthritis: a case of Gorham's
      disease.

PMID- 19582462
TI  - Assessment of alveolar epithelial permeability with Tc-99m DTPA aerosol
      scintigraphy in patients with Sjogren syndrome.
AB  - Sjogren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the
      exocrine glands and usually presents as persistent dryness of the mouth and eyes.
      Lung disease in SjS has been reported to occur early following clinical
      presentation of the disease. In this study, technetium-99m diethylene triamine
      penta-acetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy was used to
      assess the pulmonary membrane permeability in patients with primary SjS. A total
      of 18 patients with primary SjS and 13 healthy controls were investigated.
      Clinical evaluation, chest X-ray examination, pulmonary function tests, Tc-99m
      DTPA aerosol scintigraphy were performed in all the cases. The presence of
      respiratory symptoms (dyspnea and cough), duration of sicca symptoms were
      recorded. The clearance half time of Tc-99m DTPA radioaerosols in patients with
      SjS (20.49 +/- 2.56 min) was faster when compared to normal controls (42.32 +/-
      13.28 min) (P = 0.000) which means that there is a significant increase in lung
      permeability in patients with SjS compared to the controls. There is also a
      significant difference between PI of patients with SjS (0.34 +/- 0.09) and that
      of controls (0.42 +/- 0.07) (P = 0.012). According to the results of our
      preliminary study, one can detect pulmonary involvement by Tc-99m DTPA aerosol
      inhalation scintigraphy in patients with primary SjS.

PMID- 19582464
TI  - Malignant solid tumour, HIV infection and tuberculosis in children: an unholy
      triad.
AB  - INTRODUCTION: Co-morbidities introduce confounding variables into investigational
      protocols and complicate both diagnosis and management of children with malignant
      solid tumours. Such patients who are coincidentally HIV infected and who also
      have pulmonary or abdominal tuberculosis pose a particular challenge. AIM: The
      purpose of this report is to describe the diagnostic and management difficulties
      encountered in a small cadre of 18 HIV-infected children with solid tumours
      presenting to the Department of Paediatric Surgery. METHOD: A retrospective
      descriptive study of HIV-infected children with malignant solid tumours. RESULTS:
      18 HIV-infected children were identified with a variety of primary tumours. 11
      children had confirmed pulmonary or abdominal tuberculosis and in 4 the diagnosis
      was suspected. Neoadjuvant chemotherapy was used when possible to provide a
      window of opportunity to investigate co-morbidity and improve health status,
      inter alia, improving the patients' nutritional status. FDG-PET scanning proved
      unreliable in discriminating between malignant and inflammatory pathology.
      Overall survival was 33%. CONCLUSION: The coincidence of malignancy, HIV
      infection and tuberculosis carries a high mortality independent of the primary
      tumour type.

PMID- 19582463
TI  - Intralesional sclerotherapy for subcutaneous venous malformations in children.
AB  - BACKGROUND: Venous malformations (VMs) involve multiple anatomical spaces and
      encase critical neuromuscular structures, making surgical treatment difficult.
      Recently sclerotherapy has been suggested as the primary treatment for VMs
      instead of surgical intervention. This report represents eight cases of children
      with VMs treated with direct percutaneous injections of sclerosing agents, such
      as ethanol, polidocanol or ethanolamine oleate. METHODS: All eight patients had
      large lesions (>3 cm) located on the head, foot, neck and face. Sclerotherapy was
      performed in an angiographic suite under general anesthesia. Prior to
      sclerotherapy, percutaneous phlebography was performed in order to visualize the
      dynamic situation inside the lesion and the draining flow into the adjacent
      venous vascular system. A 2-15 ml of sclerosing agent was injected into VM
      lesions under fluoroscopy. RESULTS AND CONCLUSIONS: An evaluation by MRI
      examination showed that 6 out of 8 patients had remission, and alleviation of
      their symptoms without major complications, furthermore one of the lesions
      apparently disappeared. Intralesional sclerotherapy provides a simple, safe and
      effective treatment for VMs in the subcutaneous lesions in children.

PMID- 19582465
TI  - Influence of anemia on tumor response to preoperative chemoradiotherapy for
      locally advanced rectal cancer.
AB  - PURPOSE: In rectal cancer patients treated with preoperative chemoradiotherapy
      (CRT) and curative resection, we evaluated the influence of anemia on tumor
      response to preoperative CRT. METHODS: Between August 2001 and July 2007, 490
      patients underwent preoperative CRT, followed by curative-intent surgery. Tumor
      responses were evaluated based on tumor regression grade (TRG), T- and N-level
      downstaging, and volume reduction rates. RESULTS: The level of pretreatment
      hemoglobin (Hb) was 12.9 +/- 1.7 g/dl (range, 7.2-17.6 g/dl). Tumor response
      rates were significantly different below and above the Hb level of 9.0 g/dl.
      Specifically, patients with Hb levels >or=9.0 g/dl achieved better tumor
      responses than those with Hb levels < 9.0 g/dl (rates of TRG 3 or 4-29.0% vs. 0%,
      p < 0.001). In addition, there is no differences in tumor response between the
      nontransfusion and transfusion groups of patients with Hb levels >or=9.0 g/dl
      (rates of TRG 3 or 4-29.1% vs. 23.1%, p = 0.445). CONCLUSIONS: The serum Hb level
      could be a one of prognostic factors that influences the pathologic tumor
      response, and pretreatment anemia (below 9.0 g/dl of Hb) is associated with poor
      response to preoperative CRT.

PMID- 19582466
TI  - The effect of autonomous neuropathy on bowel preparation in type 2 diabetes
      mellitus.
AB  - INTRODUCTION: The need for colonoscopy is common among diabetics. In this study,
      we aimed to evaluate the effect of autonomous neuropathy on bowel preparation in
      type 2 diabetes mellitus (DM) patients. MATERIALS AND METHODS: The study
      population consisted of 45 patients with DM and 48 non-diabetic, age- and sex
      matched subjects. All colonoscopies were performed 5 h after the last dose of
      sodium phosphate. Colonoscopists rated the bowel preparation quality during the
      procedure using the Aronchick scale. All patients underwent a detailed
      cardiologic examination and 24-h Holter rhythm monitoring. Orthostatic
      hypotension and impairment in heart rate variability were accepted as indicators
      of autonomous neuropathy. RESULTS: Gender, age, blood pressure, and heart rates
      did not differ significantly between groups (p > 0.05). Autonomous neuropathy was
      detected in 14 (31.1%) patients in the DM group and in two (4.2%) in the control
      group (p < 0.05). Optimal bowel cleansing was achieved in 93.8% of controls and
      73.3% of diabetics; bowel cleansing was suboptimal in 26.7% of diabetics and 6.2%
      of controls (p < 0.05). Optimal bowel cleansing was achieved in six of 14 (42.8%)
      diabetic patients with autonomous neuropathy; however, optimal bowel cleansing
      was achieved in 27 of 31 (87.1%) diabetic patients without autonomous neuropathy
      (p < 0.05). Although optimal bowel cleansing was more prevalent among control
      patients than in diabetic patients without autonomous neuropathy, the difference
      was not significant (87.1% vs 93.8%; p > 0.05). CONCLUSION: These data suggest
      that optimal bowel cleansing is poorer in diabetics with autonomous neuropathy
      than in those without autonomous neuropathy and controls.

PMID- 19582467
TI  - [On the occasion of professor Dr. Heinrich Geidel's 80th birthday].

PMID- 19582468
TI  - [Fibromyalgia--the new guideline].
AB  - To date, the long-term course of fibromyalgia (FM) generally shows little
      improvement and many patients have problems managing their private, social and
      professional lives, if at all. Health workers in various specialties, and even in
      the same specialty, have differing concepts on etiology, diagnosis and treatment
      of FM. In its work spanning 2 years, an interdisciplinary working group made up
      from 10 scientific associations reviewed the literature and developed an S3-level
      consensus guideline. Various etiopathogenetic concepts converge from the
      perspective of a biopsychosocial model. A stepwise treatment approach with
      patient education, endurance training, multi-modal therapy and promotion of
      significant resources is recommended. Of the psychotherapeutic methods, cognitive
      behavioural training has proved the most relevant. Only a handful of drug
      therapies have undergone controlled trials, most however only over a period of a
      few weeks.

PMID- 19582469
TI  - [Muscle pain and weakness: common symptoms seen in medical practices--an
      interdisciplinary approach].

PMID- 19582470
TI  - Hybrid external fixation in treatment of proximal tibial fractures: a good
      outcome in AO/ASIF type-C fractures.
AB  - INTRODUCTION: The treatment of proximal tibial fractures is often challenging,
      and internal fixation is occasionally associated with problems in wound healing
      due to frequently co-existing soft tissue injuries. External fixation of these
      fractures have yielded satisfactory results, but some studies have reported
      problems in the achievement and maintenance of fracture reduction. The purpose of
      the present study was to evaluate the performance of a hybrid external fixator in
      the treatment of different types of proximal tibial fractures. MATERIALS AND
      METHODS: Thirty-three proximal tibial fractures, of which 20 were high energetic,
      were treated with a hybrid external fixator (Tenxor Strker-Howmedica) in the
      acute phase. Fracture categorisation was done according to AO/ASIF, and the
      reduction was performed most often by closed means or through mini-open reduction
      (26/78.8%). The patients were followed up to an average of 12.7 months (range 10
      22) and were evaluated with radiographs and clinical examinations. RESULTS: Five
      AO/ASIF type-C intraarticular fractures had a poor postoperative reduction, and
      were thus treated with internal fixation in a second operation. Of the remaining
      28 patients, local and transient pin tract infection was observed in seven
      patients, and one had septic arthritis of the knee. All 13 C1 and five of six
      C2/C3 fractures united in mean time of 15.1 weeks, whereas three of nine type-A
      fractures failed to unite, albeit an adequate reduction, and needed a second
      operation (odds ratio 11.4, 95% CI 1.0-143, compared with type-C fractures). For
      the remaining six type-A fractures, the mean healing time was 24 weeks (mean
      difference 8.9, 95% CI 6-12 weeks compared with type-C fractures). Age over 48
      and the presence of an open fracture, but not fracture type, gender, or the level
      of injury energy, correlated to a poor subjective outcome. CONCLUSIONS: The
      hybrid external fixation method we have used is safe, and type-C1 fractures are
      particularly suitable to be treated with this method. However, even C2/C3
      fractures may be candidates for this method, but a meticulous fracture reduction
      should be performed. Type-A fractures are liable to healing problems when the
      fixator is used as a rigid complex.

PMID- 19582471
TI  - Short- and long-term effects of single and repetitive glove occlusion on the
      epidermal barrier.
AB  - The aim of this study was to analyse the occlusive effects of glove materials
      (polyvinyl chloride, natural rubber latex) on epidermal barrier function and to
      relate the findings to the definitions of wet work in the current German
      ordinance on hazardous substances (2007) and in the German technical regulations
      on hazardous substances (TRGS 401; 2008). Short-term effects of wearing gloves
      once for 4 h, as well as the long-term effects of wearing gloves for 4 h daily
      for 7 days were assessed in a group of 20 healthy volunteers using non-invasive
      methods (transepidermal water loss (TEWL), capacitance, skin colour, skin surface
      pH). Data were collected 30 min and 3 h after single use, as well as 1 day after
      a 1-week application. TEWL and capacitance data showed hyperhydration of the
      horny layer 30 min after a 4-h occlusion as compared to baseline (p < 0.05).
      Three hours later, full recovery to basal values was observed. Additionally, a
      significant long-term effect after daily occlusion for 4 h for 7 days could not
      be demonstrated. In current literature, there is controversial evidence
      concerning the effects of glove occlusion. This study could not verify
      significant damage to skin barrier after 7 days of repeated occlusion 4 h daily
      in healthy volunteers. These findings require further discussion regarding the
      definitions in the current German ordinance on hazardous substances and in the
      TRGS 401.

PMID- 19582472
TI  - Is intravitreal bevacizumab treatment effective in diffuse diabetic macular
      edema?

PMID- 19582474
TI  - Level of education and the risk of lymphoma in the European prospective
      investigation into cancer and nutrition.
AB  - INTRODUCTION: Lymphomas belong to the few cancer sites with increasing incidence
      over past decades, and only a few risk factors have been established. We explored
      the association between education and the incidence of lymphoma in the
      prospective EPIC study. MATERIALS AND METHODS: Within 3,567,410 person-years of
      follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin
      lymphomas (HL)] were identified. Cox proportional hazard regression was used to
      examine the association between highest educational level (primary school or
      less, technical/professional school, secondary school, university) and lymphoma
      risk. RESULTS: Overall, no consistent associations between educational level and
      lymphoma risk were observed; however, associations were found for sub-groups of
      the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02-1.68; n
      = 583) in women with the highest education level (university) but not in men.
      Concerning sub-classes of B-NHL, a positive association between education and
      risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In
      both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly
      lower for subjects with university degree (HR = 0.46, 95% CI = 0.27-0.79) versus
      lowest educational level. No association was found for HL. CONCLUSION: We could
      not confirm an overall consistent association of education and risk of HL or NHL
      in this large prospective study; although, education was positively related to
      the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL.
      Due to limited number of cases in sub-classes and the large number of
      comparisons, the possibility of chance findings can not be excluded.

PMID- 19582473
TI  - Treatment for colorectal liver metastases: a review.
AB  - INTRODUCTION: Over the past decade, the emergence of surgical adjuncts such as
      portal vein embolization, two-stage hepatectomy, and ablative therapies not only
      decreases mortality and morbidity after an extended hepatectomy but also broadens
      the indication for surgical treatment of liver metastasis from colorectal cancer.
      Combination chemotherapeutic regimens, namely 5-fluorouracil/folinic acid with
      irinotecan or oxaliplatin, and targeted monochromal antibodies can downsize the
      tumor burden to the extent that formerly unresectable metastases can sometimes be
      excised. DISCUSSION: The 5-year survival rate following liver resection ranges
      between 25% and 58%. During the 5-fluorouracil/folinic acid with oxaliplatin and
      5-fluorouracil/folinic acid with irinotecan treatment period, the patients who
      were deemed to be resectable should be considered as surgical candidates
      regardless of the associated adverse predictive factors. The emergence of
      epidermal growth factor receptor antibody agents, which act effectively in
      patients with Kras wild-type tumor, fosters treatment individualization.
      CONCLUSION: The efficacy of the perioperative chemotherapy on survival benefit
      for resectable liver metastases has not been justified. However, the timing and
      indication of surgical treatment paradigm in colorectal liver metastasis,
      including for synchronous disease and extrahepatic disease, are dramatically
      changing with the development of chemotherapeutic agents.

PMID- 19582475
TI  - Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer
      cells.
AB  - PURPOSE: In this study, we investigated the correlation between p53 and bcl-2 in
      gambogic acid (GA)-induced apoptosis. METHOD: MTT assay was employed to evaluate
      MCF-7 cell viability after GA treatment. Cell morphological changes were observed
      follow-up under the inverted microscope after GA withdrawal. To observe the cell
      apoptosis, DAPI staining was used. Meanwhile, p53 small interfering RNA (si-RNA)
      was adopted to knock p53 down. All expressions of p53 and bcl-2 were evaluated by
      Western blot analysis. RESULTS: MTT assay showed that GA inhibited MCF-7 cell
      growth effectively in a time-dependent manner. With 0.5 h GA treatment, p53 was
      significantly increased, whereas bcl-2 was reduced potently with 6 h GA
      treatment. After GA withdrawal, p53 expressions were maintained in high levels.
      Furthermore, bcl-2 decreasing was attenuated after co-treatment with PFT alpha, a
      p53 transcription blocker. Same result was observed after p53 knock-down by p53
      si-RNA. CONCLUSIONS: Gambogic acid induced human breast cancer cells MCF-7
      apoptosis by reducing bcl-2 expression via p53.

PMID- 19582477
TI  - Additional records of metazoan parasites from Caribbean marine mammals, including
      genetically identified anisakid nematodes.
AB  - Studies of marine mammal parasites in the Caribbean are scarce. An assessment for
      marine mammal endo- and ectoparasites from Puerto Rico and the Virgin Islands,
      but extending to other areas of the Caribbean, was conducted between 1989 and
      1994. The present study complements the latter and enhances identification of
      anisakid nematodes using molecular markers. Parasites were collected from 59
      carcasses of stranded cetaceans and manatees from 1994 to 2006, including
      Globicephala macrorhynchus, Kogia breviceps, Kogia sima, Lagenodelphis hosei,
      Mesoplodon densirostris, Peponocephala electra, Stenella longirostris, Steno
      bredanensis, Trichechus manatus. Tursiops truncatus, and Ziphius cavirostris.
      Sixteen species of endoparasitic helminthes were morphologically identified,
      including two species of acanthocephalans (Bolbosoma capitatum, Bolbosoma
      vasculosum), nine species of nematodes (Anisakis sp., Anisakis brevispiculata,
      Anisakis paggiae, Anisakis simplex, Anisakis typica, Anisakis ziphidarium,
      Crassicauda anthonyi, Heterocheilus tunicatus, Pseudoterranova ceticola), two
      species of cestodes (Monorygma grimaldi, Phyllobothrium delphini), and three
      species of trematodes (Chiorchis groschafti, Pulmonicola cochleotrema,
      Monoligerum blairi). The nematodes belonging to the genus Anisakis recovered in
      some stranded animals were genetically identified to species level based on their
      sequence analysis of mitochondrial DNA (629 bp of mtDNA cox 2). A total of five
      new host records and six new geographic records are presented.

PMID- 19582476
TI  - Alterations of gene expression of RB pathway in Opisthorchis viverrini infection
      induced cholangiocarcinoma.
AB  - Opisthorchiasis has the significant relationship with the high prevalence of
      cholangiocarcinoma (CCA; a bile duct cancer) in the endemic areas in Southeast
      Asia. To reveal the molecular mechanism of the tumorigenesis induced by
      Opisthorchis viverrini infection, the present study investigated the kinetic
      expression of RB pathway genes, including RB1, p16(INK4), cyclin D1, and CDK4,
      during the development of opisthorchiasis-associated CCA in hamster model. The
      results of quantitative real-time polymerase chain reaction indicated that the
      expressions of RB1 and p16(INK4) were down-regulated during the development of
      CCA induced by infection plus N-nitrosodimethylamine treatment in a time
      dependent manner. On the other hand, the expressions of cyclin D1 and CDK4 were
      up-regulated. The expression kinetics was corresponding to the pathological
      progression of the opisthorchiasis-associated CCA, revealed by histopathological
      observation. Moreover, the analysis of the expression of these genes in human
      opisthorchiasis-associated CCA cases showed the decreased expression of RB1 and
      p16(INK4) in 50% and 82.7% cases and overexpression of cyclin D1 and CDK4 in half
      cases, respectively. The results suggested that RB pathway is likely involved in
      the tumorigenesis of opisthorchiasis-induced CCA and proposed the potential
      application of some of these genes as biomarkers in predispose and molecular
      therapy of the parasite-associated cancer.

PMID- 19582479
TI  - Complexity in water and carbon dioxide fluxes following rain pulses in an African
      savanna.
AB  - The idea that many processes in arid and semi-arid ecosystems are dormant until
      activated by a pulse of rainfall, and then decay from a maximum rate as the soil
      dries, is widely used as a conceptual and mathematical model, but has rarely been
      evaluated with data. This paper examines soil water, evapotranspiration (ET), and
      net ecosystem CO2 exchange measured for 5 years at an eddy covariance tower sited
      in an Acacia-Combretum savanna near Skukuza in the Kruger National Park, South
      Africa. The analysis characterizes ecosystem flux responses to discrete rain
      events and evaluates the skill of increasingly complex "pulse models". Rainfall
      pulses exert strong control over ecosystem-scale water and CO2 fluxes at this
      site, but the simplest pulse models do a poor job of characterizing the dynamics
      of the response. Successful models need to include the time lag between the
      wetting event and the process peak, which differ for evaporation, photosynthesis
      and respiration. Adding further complexity, the time lag depends on the prior
      duration and degree of water stress. ET response is well characterized by a
      linear function of potential ET and a logistic function of profile-total soil
      water content, with remaining seasonal variation correlating with vegetation
      phenological dynamics (leaf area). A 1- to 3-day lag to maximal ET following
      wetting is a source of hysteresis in the ET response to soil water. Respiration
      responds to wetting within days, while photosynthesis takes a week or longer to
      reach its peak if the rainfall was preceded by a long dry spell. Both processes
      exhibit nonlinear functional responses that vary seasonally. We conclude that a
      more mechanistic approach than simple pulse modeling is needed to represent daily
      ecosystem C processes in semiarid savannas.

PMID- 19582478
TI  - Trans-sialidase from Trypanosoma brucei as a potential target for DNA vaccine
      development against African trypanosomiasis.
AB  - African trypanosomiasis (AT), also known as sleeping sickness in humans and
      Nagana in animals, is a disease caused by the protozoan parasite Trypanosoma
      brucei. AT is an extremely debilitating disease in human, cattle, and wild
      animals, and the treatment is difficult with frequent relapses. This work shows
      that BALB-c mice immunized intramuscularly with a single dose (100 microg) of a
      plasmid DNA encoding the 5'-terminal region of the trans-sialidase (nTSA) gene of
      T. brucei brucei are able to produce IgG antibodies that bind to the bloodstream
      form of T. brucei-protein extract and recognize the recombinant nTSA protein,
      expressed in Escherichia coli. Furthermore, this DNA vaccination process was able
      to protect 60% of mice submitted to a challenge assay with the infective form of
      T. brucei brucei parasites. These results demonstrate that a DNA vaccine coding
      for trans-sialidase from T. brucei is potentially useful in the prophylaxis of
      AT.

PMID- 19582480
TI  - Lithium-induced membranous glomerulonephropathy in a pediatric patient.
AB  - Lithium-induced glomerular toxicity is an infrequent occurrence in pediatric
      patients. We report a 13-year-old patient presenting with clinical and laboratory
      evidence of renal insufficiency after long-term lithium use. Biopsy revealed
      membranous glomerulonephropathy. Discontinuation of the lithium treatment
      resulted in resolution of the symptoms and laboratory abnormalities. Other alkali
      metals have been implicated as risk factors for membranous glomerulonephropathy.
      To the best of our knowledge, this is the first reported case of lithium-induced
      glomerulonephropathy in a pediatric patient.

PMID- 19582481
TI  - HHV-6 infection in a pediatric kidney transplant patient.
AB  - Human herpesvirus 6 (HHV-6) infection can induce unusual complications in
      transplant patients, such as interstitial pneumonitis, encephalitis and marrow
      aplasia. We describe the clinical course of HHV-6 infection in a girl with renal
      transplantation. She presented with diarrhea and poor feeding on day 36 post
      transplantation (Tx), after a 5-day steroid pulse for clinical signs of acute
      rejection. A week later she developed fever and had elevated plasma creatinine
      and lactic dehydrogenase levels, but a physical examination did not reveal any
      anomalies with respect to suggest rash, pneumonitis, encephalitis or
      lymphadenopathy. Two weeks later, the patient developed anemia and leucopenia.
      HHV-6 was the only pathogen detected by the PCR assay of the serum and marrow
      aspiration. The patient had a successful recovery without specific treatment.
      This case report highlights the wide spectrum of complications resulting from HHV
      6 infection in immunosuppressed patients.

PMID- 19582482
TI  - Outcome and management of isolated moderate renal pelvis dilatation detected at
      postnatal screening.
AB  - The aim of this study was to evaluate the incidence and outcome of isolated
      moderate renal pelvis dilatation (RPD) [anterior-posterior diameter (APD) 10-15
      mm] in an unselected population of 2-month-old infants prospectively followed for
      up to 12-14 months of life. Isolated moderate renal pelvis dilatation was
      detected in 282 of the 11,801 (2.4%), infants screened; 240 infants with normal
      renal ultrasound were enrolled as the control group. Resolution of RPD was
      considered when an APD <or= 5 mm was found on two consecutive sonograms.
      Urological investigations were initiated if the RPD persisted or if urinary tract
      infection (UTI) occurred during follow-up, and antibiotic therapy was
      administered only when UTI occurred. The events of interest were resolution of
      the RPD, presence of uropathy and UTI. At follow-up, RPD persisted only in 18
      infants; of these, four infants were diagnosed with vesicoureteral reflux (grade
      1-3) and 14 with ureteropelvic junction obstruction. Of the 223 infants with RPD
      and 230 control infants who completed follow-up, UTI occurred in 3.6 and 2.5%,
      respectively. The incidence rate of UTI per 1000 person-months was 5.98 episodes
      in the patient group and 5.22 episodes in the control group. The rate ratio was
      1.146 (95% confidence interval 0.389-3.54, p = 0.8). Our data suggest that
      isolated moderate RPD is essentially a self-limiting condition and that
      antibiotic prophylaxis for the prevention of UTI should not be performed. A non
      invasive ultrasound scan performed during the follow-up is sufficient to diagnose
      a potentially dangerous and persistent RPD.

PMID- 19582483
TI  - Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no
      CLCN5 mutations.
AB  - Dent's disease is an X-linked renal tubulopathy caused by mutations mainly
      affecting the CLCN5 gene. Defects in the OCRL1 gene, which is usually mutated in
      patients with Lowe syndrome, have recently been shown to lead to a Dent-like
      phenotype, called Dent's disease 2. About 25% of Dent's disease patients do not
      carry CLCN5/OCRL1 mutations. The CLCN4 and SLC9A6 genes have been investigated,
      but no mutations have been identified. The recent discovery of a novel mediator
      of renal amino acid transport, collectrin (the TMEM27 gene), may provide new
      insight on the pathogenesis of Dent's disease. We studied 31 patients showing a
      phenotype resembling Dent's disease but lacking any CLCN5 mutations by direct
      sequencing of the OCRL1 and TMEM27 genes. Five novel mutations, L88X,
      P161HfsX167, F270S, D506N and E720D, in the OCRL1 gene, which have not previously
      been reported in patients with Dent's or Lowe disease, were identified among 11
      patients with the classical Dent's disease phenotype. No TMEM27 gene mutations
      were discovered among 26 patients, 20 of whom had an incomplete Dent's disease
      phenotype. Our findings confirm that OCRL1 is involved in the functional defects
      characteristic of Dent's disease and suggest that patients carrying missense
      mutations in exons where many Lowe mutations are mapped may represent a
      phenotypic variant of Lowe syndrome.

PMID- 19582484
TI  - Nutritional support for head and neck cancer patients receiving radiotherapy: a
      systematic review.
AB  - PURPOSE: Squamous cell carcinoma of the head and neck (HNSCC) is associated with
      weight loss before, during, and after treatment with radiotherapy (RT). This
      systematic review addressed the question "Which interventions aimed at optimizing
      nutrition are of benefit to HNSCC patients receiving RT?" METHODS: Randomized
      controlled trials (RCTs) studying interventions directed at nutritional support
      of adult patients with HNSCC receiving RT with or without chemotherapy were
      eligible. RCTs studying prophylaxis of acute mucositis, perioperative nutrition,
      or palliative and non-HNSCC populations were excluded. A comprehensive literature
      search was done and meta-analyses planned. RESULTS: Ten unique RCTs were
      identified (n = 585). All randomized less than 50 patients per trial arm. Five
      trials studied dietary counseling and/or nutritional supplements, four studied
      drug interventions, and one studied prophylactic enteral tube feeding.
      Nutritional status appeared to be maintained or improved with dietary counseling,
      megestrol acetate, and prophylactic enteral tube feeding. CONCLUSIONS: Data from
      RCTs supporting the use of interventions to optimize nutrition in HNSCC patients
      receiving RT are limited in both quantity and quality. Potentially effective
      interventions have not been tested comparatively or in combination, and few
      patients receiving chemoradiotherapy were studied. Further research in this area
      is a priority.

PMID- 19582485
TI  - Does mycorrhization influence herbivore-induced volatile emission in Medicago
      truncatula?
AB  - Symbiosis with mycorrhizal fungi substantially impacts secondary metabolism and
      defensive traits of colonised plants. In the present study, we investigated the
      influence of mycorrhization (Glomus intraradices) on inducible indirect defences
      against herbivores using the model legume Medicago truncatula. Volatile emission
      by mycorrhizal and non-mycorrhizal plants was measured in reaction to damage
      inflicted by Spodoptera spp. and compared to the basal levels of volatile
      emission by plants of two different cultivars. Emitted volatiles were recorded
      using closed-loop stripping and gas chromatography/mass spectrometry. The
      documented volatile patterns were evaluated using multidimensional scaling to
      visualise patterns and stepwise linear discriminant analysis to distinguish
      volatile blends of plants with distinct physiological status and genetic
      background. Volatile blends emitted by different cultivars of M. truncatula prove
      to be clearly distinct, whereas mycorrhization only slightly influenced herbivore
      induced volatile emissions. Still, the observed differences were sufficient to
      create classification rules to distinguish mycorrhizal and non-mycorrhizal plants
      by the volatiles emitted. Moreover, the effect of mycorrhization turned out to be
      opposed in the two cultivars examined. Root symbionts thus seem to alter indirect
      inducible defences of M. truncatula against insect herbivores. The impact of this
      effect strongly depends on the genetic background of the plant and, hence, in
      part explains the highly contradictory results on tripartite interactions
      gathered to date.

PMID- 19582486
TI  - The changing face of quality in spine surgery.

PMID- 19582487
TI  - Disruption of CNTNAP2 and additional structural genome changes in a boy with
      speech delay and autism spectrum disorder.
AB  - Patients with autism spectrum disorder (ASD) frequently harbour chromosome
      rearrangements and segmental aneuploidies, which allow us to identify candidate
      genes. In a boy with mild facial dysmorphisms, speech delay and ASD, we
      reconstructed by karyotyping, FISH and SNP array-based segmental aneuploidy
      profiling a highly complex chromosomal rearrangement involving at least three
      breaks in chromosome 1 and seven breaks in chromosome 7. Chromosome banding
      revealed an inversion of region 7q32.1-7q35 on the derivative chromosome 7. FISH
      with region-specific BACs mapped both inversion breakpoints and revealed
      additional breaks and structural changes in the CNTNAP2 gene. Two gene segments
      were transposed and inserted into the 1q31.2 region, while the CNTNAP2 segment
      between the two transposed parts as well as intron 13 to the 5-UTR were retained
      on the der(7). SNP array analysis revealed an additional de novo deletion
      encompassing the distal part of intron1 and exon 2 of CNTNAP2, which contains
      FOXP2 binding sites. Second, we found another de novo deletion on chromosome
      1q41, containing 15 annotated genes, including KCTD3 and USH2A. Disruptions of
      the CNTNAP2 gene have been associated with ASD and with Gilles de la Tourette
      syndrome (GTS). Comparison of disruptions of CNTNAP2 in patients with GTS and ASD
      suggests that large proximal disruptions result in either GTS or ASD, while
      relatively small distal disruptions may be phenotypically neutral. For full-blown
      ASD to develop, a proximal disruption of CNTNAP2 may have to occur concomitantly
      with additional genome mutations such as hemizygous deletions of the KCTD3 and
      USH2A genes.

PMID- 19582489
TI  - Encoding geometric and non-geometric information: a study with evolved agents.
AB  - Vertebrate species use geometric information and non-geometric or featural cues
      to orient. Under some circumstances, when both geometric and non-geometric
      information are available, the geometric information overwhelms non-geometric
      cues (geometric primacy). In other cases, we observe the inverse tendency or the
      successful integration of both cues. In past years, modular explanations have
      been proposed for the geometric primacy: geometric and non-geometric information
      are processed separately, with the geometry module playing a dominant role. The
      modularity issue is related to the recent debate on the encoding of geometric
      information: is it innate or does it depend on environmental experience? In order
      to get insight into the mechanisms that cause the wide variety of behaviors
      observed in nature, we used Artificial Life experiments. We demonstrated that
      agents trained mainly with a single class of information oriented efficiently
      when they were exposed to one class of information (geometric or non-geometric).
      When they were tested in environments that contained both classes of information,
      they displayed a primacy for the information that they had experienced more
      during their training phase. Encoding and processing geometric and non-geometric
      information was run in a single cognitive neuro-representation. These findings
      represent a theoretical proof that the exposure frequency to different spatial
      information during a learning/adaptive history could produce agents with no
      modular neuro-cognitive systems that are able to process different types of
      spatial information and display various orientation behaviors (geometric primacy,
      non-geometric primacy, no primacy at all).

PMID- 19582488
TI  - Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1
      mutation.
AB  - Schwannomatosis (MIM 162091) is a condition predisposing to the development of
      central and peripheral schwannomas; most cases are sporadic without a clear
      family history but a few families with a clear autosomal dominant pattern of
      transmission have been described. Germline mutations in SMARCB1 are associated
      with schwannomatosis. We report a family with multiple schwannomas and
      meningiomas. A SMARCB1 germline mutation in exon 1 was identified. The mutation,
      c.92A>T (p.Glu31Val), occurs in a highly conserved amino acid in the SMARCB1
      protein. In addition, in silico analysis demonstrated that the mutation disrupts
      the donor consensus sequence of exon 1. RNA studies verified the absence of mRNA
      transcribed by the mutant allele. This is the first report of a SMARCB1 germline
      mutation in a family with schwannomatosis characterized by the development of
      multiple meningiomas.

PMID- 19582490
TI  - A social preference valuations set for EQ-5D health states in Flanders, Belgium.
AB  - This study aimed at deriving a preference valuation set for EQ-5D health states
      from the general Flemish public in Belgium. A EuroQol valuation instrument with
      16 health states to be valued on a visual analogue scale was sent to a random
      sample of 2,754 adults. The initial response rate was 35%. Eventually, 548 (20%)
      respondents provided useable valuations for modeling. Valuations for 245 health
      states were modeled using a random effects model. The selection of the model was
      based on two criteria: health state valuations must be consistent, and the
      difference with the directly observed valuations must be small. A model including
      a value decrement if any health dimension of the EQ-5D is on the worst level was
      selected to construct the social health state valuation set. A comparison with
      health state valuations from other countries showed similarities, especially with
      those from New Zealand. The use of a single preference valuation set across
      different health economic evaluations within a country is highly preferable to
      increase their usability for policy makers. This study contributes to the
      standardization of outcome measurement in economic evaluations in Belgium.

PMID- 19582491
TI  - Hospital costs for treatment of acute heart failure: economic analysis of the
      REVIVE II study.
AB  - BACKGROUND: Acute heart failure (AHF) is the leading cause of hospital admission
      among older Americans. The Randomized EValuation of Intravenous Levosimendan
      Efficacy (REVIVE II) trial compared patients randomly assigned to a single
      infusion of levosimendan (levo) or placebo (SOC), each in addition to local
      standard treatments for AHF. We report an economic analysis of REVIVE II from the
      hospital perspective. METHODS: REVIVE II enrolled patients (N = 600) hospitalized
      for treatment of acute decompensated heart failure (ADHF) who remained dyspneic
      at rest despite treatment with intravenous diuretics. Case report forms
      documented index hospital treatment (drug administration, procedures, days of
      treatment by care unit), as well as subsequent hospital and emergency department
      admissions during follow-up ending 90 days from date of randomization. These data
      were used to impute cost of admission based on an econometric cost function
      derived from >100,000 ADHF hospital billing records selected per REVIVE II
      inclusion criteria. RESULTS: Index admission mean length of stay (LOS) was
      shorter for the levo group compared with standard of care (SOC) (7.03 vs 8.96
      days, P = 0.008) although intensive care unit (ICU)/cardiac care unit (CCU) days
      were similar (levo 2.88, SOC 3.22, P = 0.63). Excluding cost for levo, predicted
      mean (median) cost for the index admission was levo US $13,590 (9,458), SOC
      $19,021 (10,692) with a difference of $5,431 (1,234) favoring levo (P = 0.04).
      During follow-up through end of study day 90, no significant differences were
      observed in numbers of hospital admissions (P = 0.67), inpatient days (P = 0.81)
      or emergency department visits (P = 0.41). Cost-effectiveness was performed with
      a REVIVE-II sub-set conforming to current labeling, which excluded patients with
      low baseline blood pressure. Assuming an average price for levo in countries
      where currently approved, there was better than 50% likelihood that levo was both
      cost-saving and improved survival. Likelihood that levo would be cost-effective
      for willingness-to-pay below $50,000 per year of life gained was about 65%.
      CONCLUSIONS: In the REVIVE II trial, patients treated with levo had shorter LOS
      and lower cost for the initial hospital admission relative to patients treated
      with SOC. Based on sub-group analysis of patients administered per the current
      label, levo appears cost-effective relative to SOC.

PMID- 19582492
TI  - Growth mixture model of distraction osteogenesis: effect of pre-traction
      stresses.
AB  - In tensional studies of bone fragments during limb lengthening, it is usually
      assumed that the stress level in the gap tissue before each distraction step (pre
      traction stress) is rather modest. However, during the process of distraction
      osteogenesis, a large interfragmentary gap is generated and these pre-traction
      stresses may be important. To date, to the authors' knowledge, no computational
      study has been developed to assess the effect of stress accumulation during limb
      lengthening. In this work, we present a macroscopic growth mixture formulation to
      investigate the influence of pre-traction stresses on the outcome of this
      clinical procedure. In particular, the model is applied to the simulation of the
      regeneration of tibial defects by means of distraction osteogenesis. The
      evolution of pre-traction forces, post-traction forces and peak forces is
      evaluated and compared with experimental data. The results show that the
      inclusion of pre-traction stresses in the model affects the evolution of the
      regeneration process and the corresponding reaction forces.

PMID- 19582493
TI  - Bioactive substances produced by marine isolates of Pseudomonas.
AB  - Pseudomonas is a genus of non-fermentative gram-negative Gammaproteobacteria
      found both on land and in the water. Many terrestrial isolates of this genus have
      been studied extensively. While many produce bioactive substances, enzymes, and
      biosurfactants, other Pseudomonas isolates are used for biological control of
      plant diseases and bioremediation. In contrast, only a few marine isolates of
      this genus have been described that produce novel bioactive substances. The
      chemical structures of the bioactive substances from marine Pseudomonas are
      diverse, including pyroles, pseudopeptide pyrrolidinedione, phloroglucinol,
      phenazine, benzaldehyde, quinoline, quinolone, phenanthren, phthalate, andrimid,
      moiramides, zafrin and bushrin. Some of these bioactive compounds are
      antimicrobial agents, and dibutyl phthalate and di-(2-ethylhexyl) phthalate have
      been reported to be cathepsin B inhibitors. In addition to being heterogeneous in
      terms of their structures, the antibacterial substances produced by Pseudomonas
      also have diverse mechanisms of action: some affect the bacterial cell membrane,
      causing bacterial cell lysis, whereas others act as acetyl-CoA carboxylase and
      nitrous oxide synthesis inhibitors. Marine Pseudomonas spp. have been isolated
      from a wide range of marine environments and are a potential untapped source for
      medically relevant bioactive substances.

PMID- 19582494
TI  - Docosahexaenoic acid activates some SREBP-2 targets independent of cholesterol
      and ER stress in SW620 colon cancer cells.
AB  - The SREBP-2 transcription factor is mainly activated by low cellular cholesterol
      levels. However, other factors may also cause SREBP-2 activation. We have
      previously demonstrated activation of SREBP-2 by the polyunsaturated fatty acid
      docosahexaenoic acid (DHA) in SW620 colon cancer cells. Despite activation of
      SREBP-2, only a few target genes were induced and cholesterol biosynthesis was
      reduced. In the present study, gene expression analysis at early time points
      verified the previously observed SREBP-2 target gene expression pattern.
      Activation of SREBP-2 using siRNAs targeting Niemann Pick C1 protein (NPC1) led
      to increased expression of all SREBP target genes examined, indicating that
      activation of some SREBP-2 target genes is inhibited during DHA-treatment.
      Cholesterol supplementation during DHA treatment did not abolish SREBP-2
      activation. We also demonstrate that activation of SREBP-2 is independent of ER
      stress and eIF2alpha phosphorylation, which we have previously observed in DHA
      treated cells. Thapsigargin-induced ER stress repressed expression of SREBP-2
      target genes, but with a different pattern than observed in DHA-treated cells.
      Moreover, oleic acid (OA) treatment, which does not induce ER stress in SW620
      cells, led to activation of SREBP-2 and induced a target gene expression pattern
      similar to that of DHA-treated cells. These results indicate that DHA and OA may
      activate SREBP-2 and inhibit activation of SREBP-2 target genes through a
      mechanism independent of cholesterol level and ER stress.

PMID- 19582495
TI  - Mirror foot: treatment of three cases and review of the literature.
AB  - PURPOSE: To describe three cases of mirror foot and to develop a new
      classification of the mirror feet with an emphasis on their treatment. METHODS:
      Surgical treatment was performed on three patients with mirror foot. Mirror feet
      in the English literature were surveyed and cases found in PubMed as well as our
      three cases were classified according to a new classification that was an analogy
      of the mirror hand classification proposed by Al-Qattan et al. (J Hand Surg Br
      23:534-536, 1998). RESULTS: All three cases obtained satisfactory outcome after
      the treatment. In addition to these cases, 28 mirror feet were well described in
      the English literature, among which only seven cases have been documented for
      their treatment. All of the cases could be assigned to one of the categories of
      the proposed classification. CONCLUSION: Mirror foot is a very rare congenital
      deformity of the foot. We successfully treated three novel cases of mirror feet.
      A classification of the mirror feet proposed in this article was useful in order
      to understand its nature and obtain a guideline for its treatment.

PMID- 19582497
TI  - Length variation in 18S rRNA expansion segment 43/e4 of Daphnia obtusa: ancient
      or recurring polymorphism?
AB  - Expansion segments in ribosomal DNA (rDNA) can show length variation at the level
      of the individual, yet our understanding of the evolutionary forces shaping this
      variation is incomplete. Previous studies of expansion segment 43/e4 of the 18S
      rRNA gene in Daphnia obtusa have examined this variation in six individuals;
      however, it is not known if the variation documented at this locus is
      representative of variation across the species' geographic range. Furthermore, it
      is unclear whether length variants found in multiple individuals share common
      ancestry, or were generated de novo through recombination. We quantified
      expansion segment length variant frequencies in 134 individual D. obtusa from 33
      populations at 15 sites across the species range in the US, and used a
      phylogeographic approach to determine whether recombination continues to add to
      the standing crop of variation at this locus. We identified seven length variants
      across the sampling range, which spans almost 3000 km. Based on the
      phylogeographic distribution of length variants in the expansion segment, we
      conclude that they are shared ancient polymorphisms that have persisted despite
      the operation of molecular mechanisms that cause the concerted evolution of
      multigene families such as rDNA.

PMID- 19582498
TI  - Levels of cadmium, mercury, and lead in Magellanic penguins (Spheniscus
      magellanicus) stranded on the Brazilian coast.
AB  - Cadmium (Cd), mercury (Hg), and lead (Pb) were determined in samples of liver and
      breast muscles of first-year Magellanic penguins (Spheniscus magellanicus), from
      two different areas on the Brazilian coast, 35 on the Rio de Janeiro coast and 12
      on the Rio Grande do Sul coast. In both areas, Cd concentrations in muscle
      samples were <0.025 microg/g. However, the Cd and Hg concentrations found in
      liver and Hg concentrations found in muscle showed a significant difference
      between the two regions. The geometric mean of the concentrations was higher in
      the specimens from Rio de Janeiro (Cd--6.8 microg/g; Hg--liver, 1.6 microg/g, and
      muscle, 0.4 microg/g wet weight) than in those from Rio Grande do Sul (Cd--2.3
      microg/g; Hg--liver, 0.9 microg/g, and muscle, 0.1 microg/g wet weight). The site
      differences could be related to differences in diet influenced by geographic
      factors. Brazil's southeastern coast is highly urbanized, and its coastal waters
      are contaminated by the waste of agricultural and industrial activities. There is
      a lack of information on the levels of heavy metals in S. magellanicus, however,
      their wide distribution and top position in the trophic chain make the use of
      stranded specimens an attractive source of information for monitoring heavy
      metals in the South Atlantic coast.

PMID- 19582499
TI  - PTPN11 gene mutation and severe neonatal hypertrophic cardiomyopathy: what is the
      link?
AB  - Noonan syndrome (NS) is an autosomal dominant disorder characterized by multiple
      dysmorphic features and a broad spectrum of congenital heart defects. Specific
      mutations of the PTPN11 gene are associated with 50% of the NS cases and 90% of
      the multiple lentigines/LEOPARD syndrome (ML/LS) cases. These two allelic
      conditions have several overlapping clinical features. This study describes the
      association between the Gln510Glu mutation of the PTPN11 gene and lethal
      progressive hypertrophic cardiomyopathy (HCM) in a newborn with the NS phenotype.
      The findings confirm the intriguing relationship between site-specific mutations
      of the PTPN11 gene and rapidly progressive HCM.

PMID- 19582500
TI  - Cerebral hemorrhage associated with sildenafil (Revatio) in an infant.
AB  - A case of cerebral hemorrhage associated with sildenafil (Revatio) use in an
      infant is presented. Sildenafil is increasingly used in the treatment of primary
      and secondary pulmonary arterial hypertension and pulmonary arteriovenous
      fistula. In the reported case, sildenafil used to treat pulmonary arteriovenous
      fistula improved right-to-left shunting across the pulmonary fistula but resulted
      in cerebral hemorrhage. Cerebral hemorrhage, a previously reported complication
      of sildenafil, developed in an infant after a rapid increase in dose, to 4.7
      mg/kg/day. Therefore, sildenafil doses must be increased only with care, and
      cerebral hemorrhage must be considered a potential complication.

PMID- 19582501
TI  - Influence of bacterial lysate quality on growth of two bacterioplankton species.
AB  - All physico-chemical parameters that affect bacterial growth rate will also
      affect bacterial molecular composition, which in turn influences the chemical
      composition of bacterial lysate and its turnover rate in the ecosystem. To
      produce qualitatively different lysates, Vibrio sp. cells were grown under
      different pH, salt, or temperature conditions in rich growth media and then
      washed and lysed by autoclaving. Both the absolute concentrations and the ratios
      between elements in the lysates varied with different growth conditions, implying
      differences in lysate quality. Either Pseudoalteromonas sp. or Vibrio sp. was
      grown on the lysates at non-limiting lysate concentrations. Different lysates
      supported growth rates of Pseudoalteromonas sp. in the range from 0.25 to 1.53 h(
      1). On the other hand, growth rates of Vibrio sp. grown on its own lysates were
      around 0.4 h(-1) and were not dependent on lysate quality. Two orders of
      magnitude decrease in Zn concentration in Vibrio sp. cells grown on different
      lysates as compared to cells grown on rich growth medium suggested that Zn might
      be a factor limiting growth. In the simple microbial loop studied, the initial
      difference in lysate quality was preserved in Pseudoalteromonas sp., whereas
      Vibrio sp. decreased the initial differences in lysate quality, thereby
      neutralizing the primary effect of environmental conditions on carbon turnover.

PMID- 19582502
TI  - MR enterography with polyethylene glycol as oral contrast medium in the follow-up
      of patients with Crohn disease: comparison with CT enterography.
AB  - BACKGROUND: To compare magnetic resonance enterography (MRE) and computed
      tomography enterography (CTE) in detecting inflammatory bowel disease activity
      (IBD) in patients with Crohn's disease (CD). METHODS: A total of 29 patients (M
      20; F 9; mean age 43.8 +/- 15.9) with known CD underwent MRE. MRE was performed
      at 1.5 T using phased-array sense body coil, after oral administration of 1.5-2 L
      of PEG solution as oral contrast agent. MRE protocol included T1-weighted,
      sSShT2, sBTFE and gadolinium-enhanced THRIVE sequences acquired on coronal and
      axial planes. CTE was performed using a 16 multidetector-row computed-tomography
      before and after intravenous administration of 120 mL of iodinated contrast. MRE
      images and CTE scans were reviewed by a radiologist for bowel thickness and
      enhancement, mesenteric lymph nodes, vascular engorgement, fibrofatty
      proliferation, fistulas and abscesses. The disease activity was also defined by
      CDAI > 150. RESULTS: MRE has demonstrated a good sensitivity in detection of CD
      activity, particularly in depiction of mural thickening, mural enhancement, and
      vascular engorgement. The level of agreement between the two technique was
      excellent in evaluating wall thickening with mucosal hyperenhancement (kappa =
      1), comb (kappa = 0.90) and halo signs (kappa = 0.86). In detecting fibrofatty
      proliferation and mesenteric lymph nodes, CTE was superior to MRE (accuracy: P <
      0.05), while MRE was superior in visualization of fistulas. CONCLUSION: MRE is an
      accurate method in monitoring the activity of CD as compared to CTE and may be
      considered an alternative to CTE in assessing degree of CD and evaluating
      therapeutic effectiveness.

PMID- 19582503
TI  - The use of metatarsal bone grafts in the treatment of saddle nose deformities.

PMID- 19582504
TI  - Quick septoplasty: surgical technique and learning curve.
AB  - BACKGROUND: The importance and technical difficulties of septal surgery often are
      underestimated. Although septoplasty is among the most common procedures in nasal
      surgery, it is poorly taught and developed. METHODS: Septoplasty was performed
      for 1,035 consecutive white patients (789 males and 246 females) with a mean age
      of 35.7 years (range, 6-62 years) using a new personal surgical technique. Septal
      surgery was associated with functional endoscopic sinus surgery (FESS) in 157
      cases and rhinoplasty in 416 cases. Preoperative otorhinolaryngologic examination
      using flexible nasal endoscopy,anterior active rhinometry (AAR), and occasional
      computed tomography of the paranasal sinuses was performed.Postoperative AAR was
      carried out. Septoplasty operative time was measured. RESULTS: A significant
      reduction in nasal breathing resistances with respect to preoperative conditions
      was found in 1,017 patients (98%) after AAR (p?0.001). No septal perforation,
      nasal infection, or bleeding was noticed postoperatively.Three cases of turbino
      septal synechiae were observed. The mean septoplasty operative time was 13.83 +/-
      4.22 min (range, 8-31 min). A short learning curve (20 septoplasty procedures)
      for this new septoplasty technique was found. CONCLUSION: The proposed
      septoplasty technique is an effective and rapid procedure for the correction of
      septal deviations in both adults and children. Reproducible and easily learned,
      this technique can be associated with other surgical procedures such as FESS and
      rhinoplasty.

PMID- 19582505
TI  - Surgery for hepatocellular carcinoma located in the caudate lobe.
AB  - BACKGROUND: Surgery remains difficult for hepatocellular carcinoma (HCC)
      originating in the caudate lobe. Our objective was to evaluate the safety and
      problems associated with caudate lobectomy combined with other types of
      hepatectomy. METHODS: We performed caudate resection for HCC in 12 patients.
      Clinical and operative characteristics and survival were analyzed. RESULTS:
      Tumors were located in the Spiegel lobe in three patients, the caudate process in
      six, and the paracaval portion in three. The procedure performed most was
      isolated partial caudate lobe resection (six patients). Three patients underwent
      partial caudate lobe resection combined with other hepatectomy, and the remainder
      underwent total caudate lobe resection combined with other hepatectomy. Tumors of
      the patients who underwent combined total caudate lobe resection were mainly in
      the paracaval portion. The median operating time for the six patients who
      underwent combined resection was 400 min, and their median intraoperative blood
      loss was 1,683 ml. There were no postoperative complications in patients who
      underwent combined total caudate lobe resection, except one case of total
      resection combined with central bisegmentectomy. In that case, the remaining
      right posterior sector was twisted after liver extraction, causing blockage of
      the outflow of the right hepatic vein. The overall and recurrence-free survival
      rates did not differ between the isolated and combined resection groups.
      CONCLUSIONS: For removal of HCC located in the caudate lobe, especially the
      paracaval portion, partial or total caudate lobe resection with other types of
      hepatectomy contributes to safe, curative surgery if the liver functional reserve
      and complications associated with surgery are well understood.

PMID- 19582508
TI  - Disparities in gastric cancer outcomes among Asian ethnicities in the USA.
AB  - BACKGROUND: Survival for gastric cancer is reportedly higher in Asians than for
      other races. It is unclear whether differences in outcome exist among Asian
      ethnicities. Our objective was to assess gastric cancer survival in Asian ethnic
      groups in a large heterogeneous population. METHODS: Asian-Americans treated for
      gastric adenocarcinoma between 1988 and 2006 were identified from the Los Angeles
      County Cancer Surveillance Program. Patients were stratified and compared by
      ethnicity (Korean, Japanese, Chinese, Vietnamese or Filipino). RESULTS: Of the
      1,817 Asian-Americans in the study cohort, 45% (n = 810) were Korean, 25% (n =
      462) were Chinese, 11% (n = 193) were Japanese, 10% (n = 188) were Filipino, and
      9% (n = 164) were Vietnamese. For the entire cohort Koreans and Filipinos had the
      longest and shortest median survival (MS), respectively (22.4 and 10.3 months,
      respectively; P < 0.001). Multivariate analysis demonstrated that Japanese and
      Filipino ethnicity independently predicted worse survival compared with Korean
      ethnicity [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.08-1.73, P =
      0.008; and HR 1.71, 95% CI 1.37-2.13, P < 0.001, respectively]. In the surgical
      cohort, Koreans and Filipinos had the longest and shortest survival, respectively
      (MS of 57.8 and 21.7 months, respectively; P < 0.001). Multivariate analysis of
      the surgical cohort also demonstrated that Japanese and Filipino ethnicity
      independently predicted worse survival compared with Korean ethnicity (HR 1.61,
      95% CI 1.22-2.13, P < 0.001; and HR 1.66, 95% CI 1.24-2.22, P < 0.001,
      respectively). CONCLUSION: There are differences in gastric cancer survival among
      Asian ethnicities. Future studies addressing varying environmental exposures and
      molecular expression patterns in gastric cancer are warranted to better
      understand these disparities in outcome.

PMID- 19582506
TI  - The FLARE intraoperative near-infrared fluorescence imaging system: a first-in
      human clinical trial in breast cancer sentinel lymph node mapping.
AB  - BACKGROUND: Invisible NIR fluorescent light can provide high sensitivity, high
      resolution, and real-time image-guidance during oncologic surgery, but imaging
      systems that are presently available do not display this invisible light in the
      context of surgical anatomy. The FLARE imaging system overcomes this major
      obstacle. METHODS: Color video was acquired simultaneously, and in real-time,
      along with two independent channels of NIR fluorescence. Grayscale NIR
      fluorescence images were converted to visible "pseudo-colors" and overlaid onto
      the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final
      preclinical validation of the imaging system. A six-patient pilot study was
      conducted in women undergoing sentinel lymph node (SLN) mapping for breast
      cancer. Subjects received (99m)Tc-sulfur colloid lymphoscintigraphy. In addition,
      12.5 microg of indocyanine green (ICG) diluted in human serum albumin (HSA) was
      used as an NIR fluorescent lymphatic tracer. RESULTS: The FLARE system permitted
      facile positioning in the operating room. NIR light did not change the look of
      the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated
      in swine using clinically available NIR fluorophores and the dual NIR
      capabilities of the system. In the pilot clinical trial, a total of nine SLNs
      were identified by (99m)Tc- lymphoscintigraphy and nine SLNs were identified by
      NIR fluorescence, although results differed in two patients. No adverse events
      were encountered. CONCLUSIONS: We describe the successful clinical translation of
      a new NIR fluorescence imaging system for image-guided oncologic surgery.

PMID- 19582507
TI  - Reduced axin protein expression is associated with a poor prognosis in patients
      with squamous cell carcinoma of esophagus.
AB  - AIMS: Our study investigates the significance of the expression of Wnt pathway
      proteins including beta-catenin, Axin, beta-transducin-repeat-containing protein
      (beta-TrCP), and adenomatous polyposis coli (APC) in squamous cell carcinoma of
      the esophagus (ESCC). METHODS: Immunohistochemical analysis was performed on
      paraffin-embedded tissue specimens from 128 resected ESCC tumors to detect the
      expression of beta-catenin, Axin, beta-TrCP, and APC. Correlation between
      immunoexpression, clinicopathological parameters, and patient survival was
      analyzed. RESULTS: Increased beta-catenin expression was noted in 22 (18.2%) of
      121 tumor specimens. Reduced expression of Axin, beta-TrCP, and APC was observed
      in 57 (46.0%) of 124, 29 (24.4%) of 119, and 54 (48.2%) of 119 specimens,
      respectively. No correlation was found among these protein expressions. Axin
      protein expression was inversely correlated with tumor invasion depth (P =
      0.033). Reduced Axin protein expression, lymph node involvement, and distant
      metastasis were significant negative predictors for overall survival and disease
      free survival on univariate analysis. In multivariate analysis, reduced Axin
      expression remained a significant prognostic factor for patients with ESCC (P =
      0.005). CONCLUSIONS: Reduced Axin expression was observed in 46% of ESCC tumor
      specimens and was associated with poor prognosis in patients with ESCC. Further
      study is mandatory to elucidate the underlying mechanism responsible for loss of
      Axin expression and the role of Axin in ESCC tumorigenesis.

PMID- 19582509
TI  - Mitochondrial genomic instability in colorectal cancer: no correlation to nuclear
      microsatellite instability and allelic deletion of hMSH2, hMLH1, and p53 genes,
      but prediction of better survival for Dukes' stage C disease.
AB  - PURPOSE: Malfunction of mismatch repair (MMR) system and p53 produces nuclear
      genomic instability and is involved in colorectal tumorigenesis. In addition to a
      nuclear genome, eukaryotic cells have cytoplasmic genomes that are
      compartmentalized in the mitochondria. The aims of this study were to detect the
      mitochondrial genomic instability (mtGI) in colorectal carcinomas, and to explore
      its relationship with nuclear genetic alterations and its prognostic meaning.
      METHODS: Eighty-three colorectal carcinomas with corresponding normal mucosa were
      analyzed for mtGI, nuclear microsatellite instability (nMSI), and loss of
      heterozygosity (LOH) of hMSH2, hMLH1, and p53 genes. Mitochondrial and nuclear
      alterations were examined for mutual correlation and for associations with
      clinicopathological features and clinical outcomes. RESULTS: Out of 83 cases,
      mtGI was identified in 23 carcinomas (27.7%), whereas nMSI was detected in 11
      (13.3%). Of the 23 cases with mtGI, only two showed nMSI simultaneously. The
      frequencies of LOH of hMSH2, hMLH1, and p53 were 16.1%, 11.6%, and 65.3%,
      respectively. There was no significant association between mtGI and these allelic
      losses. Notably, Dukes' C patients with mtGI had better disease-free and overall
      survival than those lacking this feature (p = 0.0516 and 0.0313, respectively).
      CONCLUSIONS: Mitochondrial genomic instability occurs with a high frequency in
      colorectal carcinomas but is independent of nMSI and allelic deletion of hMSH2,
      hMLH1, and p53 genes. The results suggest that, instead of nuclear MMR system,
      there might be different mechanisms involving mitochondrial genomic integrity,
      and mtGI confers a better prognosis in Dukes' C colorectal cancer.

PMID- 19582511
TI  - Community-Acquired Methicillin-Resistant Staphylococcus aureus in the Suburban
      Hand Surgery Patient Population.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause for
      patients to present to a physician's office or emergency department. We observed
      increasing numbers of community-acquired MRSA infections in patients admitted to
      the hand surgery service at our suburban academic center. It is an important
      issue as unsuspected community-acquired MRSA hand infections can be admitted to
      the hospital, inadequately treated, and allowed for nosocomial spread. This study
      was performed to examine the trend in the incidence of community-acquired MRSA
      infections in patients admitted to the hand surgery service in order to sensitize
      practitioners to have a high index of suspicion for this entity and promote early
      recognition and treatment of this organism. A multihospital retrospective chart
      review was undertaken to compare the total number of community-acquired MRSA
      infections in our hospital as well as the number in patients admitted to the hand
      surgery service with community-acquired MRSA from 2000 through 2008. Statistical
      analysis was provided by linear regression. Two community-acquired hand MRSA
      infections were treated in 2000, as compared to three in 2001 and 2002, four in
      2003, five in 2004, six in 2005, 14 in 2006, 13 in 2007, and ten in 2008. This
      increase was statistically significant (p = 0.038). This retrospective review
      documents a rapidly rising number of community-acquired MRSA hand infections in
      the suburban environment. The hand surgeon must be aware of the increased
      prevalence of this entity to adequately combat this organism and prevent
      prolonged hospital stays, expanded morbidity, and inflated treatment costs.

PMID- 19582510
TI  - Modification of aminosilanized superparamagnetic nanoparticles: feasibility of
      multimodal detection using 3T MRI, small animal PET, and fluorescence imaging.
AB  - PURPOSE: The aim of our study was to modify an aminosilane-coated
      superparamagnetic nanoparticle for cell labeling and subsequent multimodal
      imaging using magnetic resonance imaging (MRI), positron emission tomography
      (PET), and fluorescent imaging in vivo. PROCEDURES: We covalently bound the
      transfection agent HIV-1 tat, the fluorescent dye fluorescein isothiocyanate, and
      the positron-emitting radionuclide gallium-68 to the particle and injected them
      intravenously into Wistar rats, followed by animal PET and MRI at 3.0 T. As a
      proof of principle hepatogenic HuH7 cells were labeled with the particles and
      observed for cell toxicity as well as detectability by MRI and biodistribution in
      vivo. RESULTS: PET imaging and MRI revealed increasing hepatic and splenic
      accumulation of the particles over 24 h. Adjacent in vitro studies in hepatogenic
      HuH7 cells showed a rapid intracellular accumulation of the particles with high
      labeling efficiency and without any signs of toxicity. In vivo dissemination of
      the labeled cells could be followed by dynamic biodistribution studies.
      CONCLUSIONS: We conclude that our modified superparamagnetic nanoparticles are
      stable under in vitro and in vivo conditions and are therefore applicable for
      efficient cell labeling and subsequent multimodal molecular imaging. Moreover,
      their multiple free amino groups suggest the possibility for further
      modifications and might provide interesting opportunities for various research
      fields.

PMID- 19582512
TI  - Prognostic factors and adjuvant chemoradiation therapy after
      pancreaticoduodenectomy for pancreatic adenocarcinoma.
AB  - BACKGROUND: The aim of this study was to determine prognostic factors for
      survival after resection of pancreatic adenocarcinoma (PC) and to compare
      outcomes after surgery alone versus surgery plus adjuvant therapy. METHODS: We
      performed a retrospective review of 219 patients who underwent
      pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data
      were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT)
      consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation
      dose was 45 Gy. RESULTS: The 3- and 5-year overall survival (OS) rates were 24.3%
      and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI),
      12-16 months]. Patients with metastatic lymph nodes experienced improved median
      survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after
      adjuvant CRT compared with those who had no CRT. Patients who underwent non
      curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037).
      Lymph node metastasis and non-curative resection showed no significance on
      multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001]
      and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic
      factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087).
      CONCLUSIONS: Adjuvant CRT benefited a subset of patients with resected PC,
      particularly those with lymph node metastasis and those undergoing non-curative
      resection. Multivariate analysis demonstrated that patients with tumors larger
      than 3 cm and poor differentiation had poor prognosis.

PMID- 19582513
TI  - Management of acute post-operative portal venous thrombosis.
AB  - BACKGROUND: Portal vein thrombosis can be a devastating, but often overlooked,
      complication of hepatobiliary procedures. Symptoms of acute portal vein
      thrombosis range from nondescript abdominal pain to septic shock secondary to
      mesenteric ischemia. DISCUSSION: The surgeon must be cognizant of these symptoms
      and the potential for portal vein thrombosis after any hepatobiliary procedures
      as an expedient diagnosis and treatment is necessary in order to prevent thrombus
      propagation, bowel ischemia, and death. This report outlines the symptoms,
      diagnosis, and a review of the literature on the treatment of acute portal vein
      thrombosis after hepatobiliary surgery with a special note made regarding a case
      of portal vein thrombosis after pancreatectomy and autologous islet cell
      transplantation.

PMID- 19582514
TI  - Long-term results of hepatectomy after hepatic arterial infusion chemotherapy for
      initially unresectable hepatic colorectal metastases.
AB  - BACKGROUND: The prognosis of unresectable hepatic colorectal metastases is poor
      even if chemotherapy is administered. The purpose of this study was to evaluate
      the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and
      hepatectomy following HAI for such condition. METHODS: Seventy-two patients with
      unresectable hepatic colorectal metastases received continuous HAI of 5
      fluorouracil. RESULTS: The overall response rate was 38%. The median survival of
      all patients was 18 months. The overall 3-year survival rate was 18%. Seven
      patients (10%) survived more than 58 months. Of the eight patients with a
      complete response, seven developed liver and/or lung metastases, and of these,
      one patient undergoing additional hepatectomy has been disease-free and the other
      six receiving chemotherapy died of disease. Another complete-response case died
      of liver abscess. Of the 19 patients with a partial response, six could undergo
      hepatectomy after HAI. The overall 5-year survival rate of seven patients
      undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the
      rate was 0%. CONCLUSIONS: Most patients showing response after HAI for
      unresectable hepatic colorectal metastases had relapses. The long-term prognosis
      of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI
      makes liver metastases resectable, they should be resected.

PMID- 19582515
TI  - Negative impact of blood transfusion on recurrence and prognosis of
      hepatocellular carcinoma after hepatic resection.
AB  - BACKGROUND: In perioperative management of hepatic resection for hepatocellular
      carcinoma, excessive blood loss and blood transfusion greatly influence
      postoperative complications and prognosis of the patients. We evaluated the
      influence of blood products use on postoperative recurrence and prognosis of
      patients with hepatocellular carcinoma. METHODS: The subjects were 66 patients
      who underwent elective hepatic resection for hepatocellular carcinoma without
      concomitant microwave or radiofrequency ablation therapy nor other malignancies
      between January 2001 and June 2006. We retrospectively investigated the influence
      of the use of blood products including red cell concentration and fresh frozen
      plasma on recurrence of hepatocellular carcinoma and overall survival. RESULTS:
      In multivariate analysis, the dose of blood products transfusion was a
      significant predictor of disease-free and overall survival. Both disease-free and
      overall survival rates of those who were given blood products were significantly
      worse than those who did not receive. On the other hand, in univariate analysis
      of disease-free and overall survival after hepatic resection and clinical
      variables, the amount of blood loss was not a significant predictor of recurrence
      or death. CONCLUSION: Transfusion of blood products is associated with increased
      recurrence rate and worse survival after elective hepatic resection for patients
      with hepatocellular carcinoma.

PMID- 19582516
TI  - Post-cholecystectomy quality of life: a prospective multicenter cohort study of
      its associations with preoperative functional status and patient demographics.
AB  - PURPOSE: This study analyzed patient demographics and preoperative functional
      status for associations with post-cholecystectomy quality of life (QOL). METHODS:
      This prospective study analyzed 159 cholecystectomy patients at two tertiary
      academic hospitals. All patients completed the SF-36 and the gastrointestinal
      quality of life index (GIQLI) at baseline and at 3 and 6 months postoperatively.
      The 95% confidence intervals for differences in responsiveness estimates were
      derived by bootstrap estimation. Scores derived by these instruments were
      interpreted by generalized estimating equation (GEE) before and after
      cholecystectomy. RESULTS: The examined population significantly (p < 0.05)
      improved in both SF-36 subscales and GIQLI subscales. After adjusting for time
      effects (time, and time(2)) and baseline predictors, GEE approaches revealed the
      following explanatory variables for QOL: time, time(2), age, gender, preoperative
      GIQLI score, body mass index, and number of comorbidities. CONCLUSION: The data
      revealed dramatically improved post-cholecystectomy QOL. However, QOL change was
      simultaneously associated with preoperative functional status and demographic
      characteristics.

PMID- 19582517
TI  - Short-term outcomes of laparoscopic rectal surgery for primary rectal cancer in
      elderly patients: is it safe and beneficial?
AB  - PURPOSE: The role of laparoscopic resection in management of rectal cancer is
      still controversial. The purpose of this study was to evaluate whether
      laparoscopic rectal resection for rectal cancer could be safely performed in
      elderly patients. METHODS: Forty-four elderly patients (> or =75 years)
      undergoing laparoscopic rectal resection (group A) were compared with 228 younger
      patients (<75 years) undergoing laparoscopic rectal resection (group B) and 43
      elderly patients (> or =75 years) undergoing open rectal resection (group C).
      RESULTS: The American Society of Anesthesiologists' status was significantly
      higher in group A than in group B. Operative procedure, operating time, and
      estimated blood loss were comparable, and overall postoperative complications did
      not differ significantly between groups A and B (13.6% vs. 11.8%). Operating time
      was longer (256 vs. 196 min), but estimated blood loss was significantly less (25
      vs. 241 ml) in group A than in group C. The rate of postoperative complications
      was lower (13.6% vs. 25.6%) in group A than in group C, but the difference was
      not statistically significant. Time to flatus (1.3 vs. 3.7 days), time to liquid
      diet (2.2 vs. 7.0 days), and hospital stay (19 vs. 22 days) were significantly
      shorter in group A than in group C. CONCLUSIONS: Laparoscopic rectal resection
      for elderly patients can be safely performed with similar postoperative outcomes
      as in younger patients and may have advantages in terms of faster
      gastrointestinal recovery and shorter length of hospital stay compared with open
      surgery.

PMID- 19582518
TI  - A case of fulminant portal pyemia complicating hemicolectomy for polyps:
      literature review and case report.
AB  - INTRODUCTION: Portal pyaemia is a rare phenomenon that can complicate a variety
      of pathologies and surgical procedures. It has a predilection for elderly and
      immunocompromised patients. DISCUSSION: We present a review of the related
      literature and report an exceptional case of fulminant portal pyaemia, with an
      atypical presentation in a patient with few typical risk factors, complicating an
      elective surgical procedure for benign disease. CONCLUSION: Portal pyaemia is a
      condition which can lead to acute overwhelming sepsis and carries a high
      mortality. It should be considered a differential in abdominal sepsis when no
      overt abdominal source is found.

PMID- 19582519
TI  - An analysis of trends and growth factor receptor expression of GI carcinoid
      tumors.
AB  - INTRODUCTION: The purpose of our study was twofold: (1) to determine the
      incidence, patient and tumor characteristics, and outcome of patients with
      gastrointestinal carcinoid tumors using the Surveillance, Epidemiology and End
      Results (SEER) database, and (2) to delineate the expression pattern of growth
      factor receptors (GFRs) in carcinoid tumors. MATERIALS AND METHODS: The SEER
      database search provided information on patients diagnosed with carcinoid tumors
      from 1990 to 2002. Carcinoid tumor sections (n = 46) were stained for the GFRs:
      epidermal growth factor receptor, insulin-like growth factor receptor (IGFR),
      vascular endothelial growth factor receptor (VEGFR), and HER-2/neu. RESULTS: Over
      the 12-year analysis period, 18,180 patients were identified with carcinoid
      tumors of the foregut, midgut, and hindgut; the incidence of carcinoid tumors
      increased approximately 2-fold during this time period. Of the patients with
      carcinoid tumors, there was a trend of increased expression of VEGFR and IGFR,
      particularly in the foregut and midgut carcinoids. Analysis of the SEER database
      confirms that the incidence of carcinoid tumors is increasing with an approximate
      doubling in the number of carcinoid cases from 1990 to 2002. Furthermore, an
      increase in VEGFR and IGFR expression suggests that GFR inhibitors may be
      effective adjuvant therapy for carcinoid cancer.

PMID- 19582521
TI  - Immunohistochemical expression of osteopontin in gastric cancer.
AB  - BACKGROUND/AIMS: Osteopontin (OPN) is significantly overexpressed in a variety of
      malignancies. However, little is known concerning the significance of OPN
      expression in human cancers. Thus, the aim of this study was to determine the
      relationship between the degree of OPN expression, the proliferative activity of
      cancer cells, and the clinicopathological findings for surgically resected
      gastric cancer. METHODOLOGY: We evaluated the immunohistochemical expression of
      OPN in 85 specimens of cancer. Additionally, we investigated a cancer cell
      proliferative index using an anti-MIB-1 antibody and terminal deoxynucleotidyl
      transferase-mediated dUTP biotin nick end labeling staining. Levels of OPN
      expression in gastric cancers were classified into three groups. To compare the
      relationship between OPN expression and clinicopathological findings, the
      features of cancer lesions were classified using the TNM Classification of
      Malignant Tumors, 6th Edition. RESULTS: Immunohistochemical examination of OPN
      expression in gastric cancer revealed diffuse granular staining in the cytoplasm.
      High OPN expression was observed in 37 of 85 carcinomas. Strong OPN expression
      was significantly associated with a low apoptotic index, a high proliferative
      index, depth of invasion, lymphatic invasion, and venous invasion.
      Pathologically, intestinal type carcinoma showed strong expression of OPN.
      CONCLUSIONS: These data suggested that OPN may play an important role in the
      invasiveness and the progressive nature of gastric cancer.

PMID- 19582520
TI  - Impact of hospital case volume on the quality of laparoscopic colectomy in Japan.
AB  - INTRODUCTION: The increased use of laparoscopic colectomy for colon cancer
      requires the evaluation of hospital case volume, quality care, and training
      systems, considering the difficulty of this surgery for various tumor locations.
      MATERIALS AND METHODS: We assessed the quality of this procedure in Japan, based
      on hospital case volume and tumor location. A total of 3,765 patients were
      enrolled across 567 hospitals between July and December 2007. We analyzed patient
      characteristics, postoperative surgical complications, the administration of
      stapling devices or chemotherapy, hospital volume and teaching status,
      postoperative length of stay, total charges, and operating room time. Hospitals
      were classified into four case-volume categories: high (> or =5 cases per month),
      intermediate to high (3-4), low to intermediate (1-2), and low (<1). Multivariate
      analysis was used to test the impact of hospital category and tumor location.
      RESULTS: Ten high-volume hospitals performed 401 cases, while 355 low-volume
      hospitals did 903. Hospital case volume, operating time, and complications
      affected postoperative stay and total costs. Longer procedural time was an
      independent predictor of complications. Tumor location, case volume, and teaching
      status explained the variations in procedural time individually but not
      complications. Training systems highlighting the applicability of techniques are
      important to promote the quality of laparoscopic colectomy.

PMID- 19582522
TI  - Seating of ceramic liners in the uncemented trident acetabular shell: is there
      really a problem?
AB  - Concerns have been raised regarding the risk of incomplete seating of metal
      backed ceramic liners in the Trident acetabular system. This prompted us to audit
      our series of primary and revision THAs. We retrospectively reviewed 68 patients
      (78 arthroplasties, 55 of which were primary and 23 revisions) using the Trident
      acetabular system between 2003 and 2007. Anteroposterior and lateral radiographs
      were reviewed independently by two specialist registrars and one consultant
      surgeon to look for incomplete seating. Six liners were seated incompletely,
      representing 8% overall. All unseated liners were in the primary group,
      representing 10% risk in this group, compared with 0% risk in the revision group.
      The incidence of malseating in our primary arthroplasty group was similar to the
      published incidence (16.4%). We encountered no problems in patients having a
      revision. We suspect shell deformation contributes to malseating of the metal
      backed ceramic liners. To reduce the rate of malseating, we now underream by 0.8
      mm rather than the usual 1.8 mm, particularly if the bone is sclerotic. LEVEL OF
      EVIDENCE: Level IV, case series. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19582523
TI  - Who is lost to followup?: a study of patients with distal radius fractures.
AB  - Distal radius fractures are the most common upper extremity fracture,
      representing one-sixth of all fractures treated in emergency departments
      nationwide. Beyond the initial reduction and immobilization of these fractures,
      providing proper followup to ensure maintenance of the reduction and identify
      complications is necessary for optimal recovery of forearm and wrist functions.
      We sought to identify the clinical and demographic factors that characterize
      patients with distal radius fractures who do not return for followup and to
      assess the underlying causes for their poor followup rates. Compared with
      patients who were compliant with followup, those lost to followup had lower
      Physical and Mental Health scores on the SF-36 forms, more often were treated
      nonoperatively, and more likely had not surpassed secondary education. However,
      we found no difference between these two groups based on age, gender, mechanism
      of injury, marital status, or hand dominance. Early identification of patients
      who potentially are noncompliant can result in additional measures being taken to
      ensure the patient's return to the treating hospital and physicians. This in turn
      will prevent complications attributable to lack of followup and allow more
      accurate assessment of results, thereby improving patient outcomes.

PMID- 19582525
TI  - Does severity or specific joint laxity influence clinical outcomes of anterior
      cruciate ligament reconstruction?
AB  - It generally is believed generalized joint laxity is one of the risk factors for
      failure of anterior cruciate ligament (ACL) reconstruction. However, no consensus
      exists regarding whether adverse effects on ACL reconstruction are attributable
      to joint-specific laxity or are related to the severity of generalized joint
      laxity. We therefore asked whether knee stability and functional outcomes would
      be related to joint-specific laxity and would differ according to the severity of
      generalized joint laxity. The Beighton and Horan criteria were used to assess
      joint laxity in 272 subjects. All elements are added to give an overall joint
      laxity score ranging from 0 to 5. Knee translation did not increase in proportion
      to the severity of the generalized joint laxity. Patients with scores less than 4
      showed similar knee stability. When all variables, including the severity of
      generalized joint laxity, were considered, only hyperextension of the knee
      independently predicted knee stability and function. In patients with knee
      hyperextension, a bone-patellar tendon-bone autograft provided superior stability
      and function compared with a hamstring tendon autograft. Our data suggest knee
      hyperextension predicts postoperative stability and function regardless whether
      patients have severe generalized joint laxity. LEVEL OF EVIDENCE: Level III,
      prognostic study. See Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 19582524
TI  - Percutaneous treatment of less severe intraarticular calcaneal fractures.
AB  - Percutaneous treatment of calcaneal fractures is intended to reduce soft tissue
      complications and postoperative stiffness of the subtalar joint. We assessed the
      complications, clinical hindfoot alignment, motion, functional outcome scores,
      and radiographic correction of percutaneous arthroscopically assisted reduction
      and screw fixation of selected, less severe fractures. We performed percutaneous
      reduction and screw fixation in 61 patients with Type II (Sanders et al.)
      calcaneal fractures. In 33 of 61 patients with displaced intraarticular fractures
      (types IIA and IIB), anatomic reduction of the subtalar joint was confirmed
      arthroscopically; these patients form the basis of this report. We observed no
      wound complications or infections. In two patients, one prominent screw was
      removed after 1 and 3 years, respectively. In one patient, arthroscopic
      arthrolysis was performed 1 year after the index procedure. Twenty-four of 33
      patients (73%) were followed a minimum of 24 months (mean, 29 months; range, 24
      67 months). The average American Orthopaedic Foot and Ankle Society ankle
      hindfoot score at last followup was 92.1 (range, 80-100). Bohler's angle and
      calcaneal width were reduced close to the values of the uninjured side. We
      believe percutaneous fixation is a reasonable alternative for moderately
      displaced Type II fractures provided adequate control over anatomic joint
      reduction with either subtalar arthroscopy or high-resolution (3-D) fluoroscopy.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 19582526
TI  - Successful spinal fusion by E. coli-derived BMP-2-adsorbed porous beta-TCP
      granules: a pilot study.
AB  - Bone morphogenetic proteins (BMPs) were originally identified as osteoinductive
      proteins. With cloning of BMP genes, studies of BMPs and their clinical
      application have advanced. However, with increasing clinical applications, drug
      delivery systems and production costs have become more important issues. To
      address these issues, we asked whether E. coli-derived rhBMP-2 (E-BMP-2)-adsorbed
      porous beta-TCP granules could achieve posterolateral lumbar fusion in a rabbit
      model similar to autogenous bone grafts. Lumbar spinal fusion masses were
      evaluated by 3-D computed tomography, mechanical testing, and histological
      analyses 8 weeks after surgery. By these measures E-BMP-2-adsorbed beta-TCP
      granules achieved lumbar spinal fusion in dose-dependent fashion in a rabbit
      model as well as autogenous bone graft. Our preliminary findings suggest E-BMP-2
      adsorbed porous beta-TCP could be a novel, effective alternative to autogenous
      bone grafting for generating new bone and promoting regenerative repair of bone,
      and potentially utilizable in the clinical setting for treating spinal disorders.

PMID- 19582527
TI  - Is fibular fracture displacement consistent with tibiotalar displacement?
AB  - We believed open reduction with internal fixation is required for supination
      external rotation ankle fractures located at the level of the distal tibiofibular
      syndesmosis (Lauge-Hanssen SER II and Weber B) with 2 mm or more fibular fracture
      displacement. The rationale for surgery for these ankle fractures is based on the
      notion of elevated intraarticular contact pressures with lateral displacement. To
      diagnose these injuries, we presumed that in patients with a fibular fracture
      with at least 2 mm fracture displacement, the lateral malleolus and talus have
      moved at least 2 mm in a lateral direction without medial displacement of the
      proximal fibula. We reviewed 55 adult patients treated operatively for a
      supination-external rotation II ankle fracture (2 mm or more fibular fracture
      displacement) between 1990 and 1998. On standard radiographs, distance from the
      tibia to the proximal fibula, distance from the tibia to the distal fibula, and
      displacement at the level of the fibular fracture were measured. These distances
      were compared preoperatively and postoperatively. We concluded tibiotalar
      displacement cannot be reliably assessed at the level of the fracture. Based on
      this and other studies, we believe there is little evidence to perform open
      reduction and internal fixation of supination-external rotation II ankle
      fractures. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 19582529
TI  - Are away rotations critical for a successful match in orthopaedic surgery?
AB  - Surveys have suggested one of the most important determinants of orthopaedic
      resident selection is completion of an orthopaedic clerkship at the program
      director's institution. The purpose of this study was to further elucidate the
      significance of visiting externships on the resident selection process. We
      retrospectively reviewed data for all medical students applying for orthopaedic
      surgery residency from six medical schools between 2006 and 2008, for a total of
      143 applicants. Univariate and multivariate regression analyses were used to
      compare students who matched successfully versus those who did not in terms of
      number of away rotations, United States Medical Licensing Examination scores,
      class rank, and other objective factors. Of the 143 medical students, 19 did not
      match in orthopaedics (13.3%), whereas the remaining 124 matched. On multiple
      logistic regression analysis, whether a student did more than one home rotation,
      how many away rotations a student performed, and United States Medical Licensing
      Examination Step 1 score were factors in the odds of match success. Orthopaedic
      surgery is one of the most competitive specialties in medicine; the away rotation
      remains an important factor in match success.

PMID- 19582528
TI  - Tantalum components in difficult acetabular revisions.
AB  - Although porous-coated hemispherical components are usually successful in
      acetabular revisions, the rate of failure is increased in hips with severe bone
      loss. Tantalum acetabular implants are characterized by higher friction, higher
      porosity, and greater osteoconductivity than titanium mesh or chrome-cobalt
      beads. We asked whether these components would provide stable short-term fixation
      without radiographic loosening in revisions at higher risk for failure. We
      prospectively followed 37 patients (39 hips) who had an acetabular revision with
      tantalum acetabular components. The minimum followup time was 2 years (mean, 3.3
      years; range, 2-7 years). The acetabular defects were classified as Paprosky et
      al. Type 3 in 26, Type 2 in 11, and Type 1 in two hips. The mean postoperative
      Harris hip score was 86. Thirty-eight of the 39 (97%) tantalum components were
      radiographically well fixed. There was one mechanical failure at 6 months,
      rerevised with a larger tantalum component. Bone ingrowth was apparent in 38 hips
      and four hips had a radiolucent line. There were six other reoperations, three
      recurrent dislocations (constrained liners leaving the shell in place), two
      infections that seeded to the hip from elsewhere and treated with drainage, and
      one supracondylar femur fracture, but the tantalum component was left in place.
      Tantalum acetabular components provide stable fixation in difficult acetabular
      revisions. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 19582530
TI  - Developing a new PET myocardial perfusion tracer.

PMID- 19582531
TI  - A multicenter evaluation of a new post-processing method with depth-dependent
      collimator resolution applied to full-time and half-time acquisitions without and
      with simultaneously acquired attenuation correction.
AB  - BACKGROUND: The field of nuclear cardiology is limited by image quality and
      length of procedure. The use of depth-dependent resolution recovery algorithms in
      conjunction with iterative reconstruction holds promise to improve image quality
      and reduce acquisition time. This study compared the Astonish algorithm employing
      depth-dependent resolution recovery and iterative reconstruction to filtered
      backprojection (FBP) using both full-time (FTA) and half-time (HTA) data.
      Attenuation correction including scatter correction in conjunction with the
      Astonish algorithm was also evaluated. METHODS: We studied 187 consecutive
      patients (132 with cardiac catheterization and 55 with low likelihood for CAD)
      from three nuclear cardiology laboratories who had previously undergone
      clinically indicated rest/stress Tc-99m sestamibi or tetrofosmin SPECT.
      Acquisition followed ASNC guidelines (64 projections, 20-25 seconds). Processing
      of the full-time data sets included FBP and Astonish (FTA). A total of 32
      projection data sets were created by stripping the full-time data sets and
      processing with Astonish (HTA). Attenuation correction was applied to both full
      time and half-time Astonish-processed images (FTA-AC and HTA-AC, respectively). A
      consensus interpretation of three blinded readers was performed for image
      quality, interpretative certainty, and diagnostic accuracy, as well as severity
      and reversibility of perfusion and functional parameters. RESULTS: Full-time and
      half-time Astonish processing resulted in a significant improvement in image
      quality in comparison with FBP. Stress and rest perfusion image quality
      (excellent or good) were 85%/80% (FBP), 98%/95% (FTA), and 95%/92% (HTA),
      respectively (p < 0.001). Interpretative certainty and diagnostic accuracy were
      similar with FBP, FTA, and HTA. Left ventricular functional data were not
      different despite a slight reduction in half-time gated image quality.
      Application of attenuation correction resulted in similar image quality and
      improved normalcy (FTA vs. FTA-AC: 76% vs. 95%; HTA vs. HTA-AC: 76% vs. 100%) and
      specificity (FTA vs. FTA-AC: 62% vs. 78%; HTA vs. HTA-AC: 63% vs. 84%) (p < 0.01
      for all comparisons). CONCLUSION: Astonish processing, which incorporates depth
      dependent resolution recovery, improves image quality without sacrificing
      interpretative certainty or diagnostic accuracy. Application of simultaneously
      acquired attenuation correction, which includes scatter correction, to full-time
      and half-time images processed with this method, improves specificity and
      normalcy while maintaining high image quality.

PMID- 19582532
TI  - A novel approach to maintain positive pressure ventilation during difficult
      Montgomery T-tube placement.

PMID- 19582533
TI  - Weaning critically ill adults from invasive mechanical ventilation: a national
      survey.
AB  - PURPOSE: To determine the stated practices of clinicians in weaning critically
      ill adults from invasive ventilation. METHODS: We conducted a cross-sectional,
      self-administered postal survey of Critical Care physicians and respiratory
      therapists (RTs) in leadership roles at Canadian teaching hospitals. We
      identified respondents using electronic mail and telephone correspondence. We
      used rigorous survey methodology to develop, test, and administer the
      questionnaire. RESULTS: One hundred ten of 162 (67.9%) clinicians returned the
      survey with 99 respondents (55 physicians and 44 RTs) completing it either in
      part or in-full. Approximately 95% of respondents acknowledged ever performing
      spontaneous breathing trials (SBTs) in clinical practice. Of these, 95.6% and 32%
      of respondents reported conducting daily and twice-daily screening to identify
      SBT candidates, at least sometimes. The three most common techniques to conduct
      SBTs included; pressure support (PS) with positive end-expiratory pressure
      (70.8%), continuous positive airway pressure (35.7%), and use of a T-piece
      (25.0%). PS ventilation was the weaning strategy used most frequently before
      SBTs. Most respondents (57.1%) considered continuous infusion of sedative
      hypnotics to be a relative contraindication to tracheal extubation. However,
      concurrent administration of low dose vasopressors, inotropes, and analgesic
      boluses, or continuous analgesic infusions were considered acceptable amongst
      60.8%, 73.2%, 78.4% and 58.8% of respondents, respectively. We did not observe
      regional variation in whether clinicians ever perform SBTs, the ventilatory modes
      used prior to an SBT nor in the use of PS and SBTs during the weaning process.
      CONCLUSIONS: Pressure support and SBTs are common features of weaning in Canadian
      teaching hospitals. Compared to the published literature, our survey suggests
      that weaning practices have evolved over time and that practice variation may be
      greater on an international level compared to a national level.

PMID- 19582534
TI  - Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual
      mechanism involving MMP-3.
AB  - In Parkinson disease (PD), the dopaminergic (DAergic) neurons in the substantia
      nigra undergo degeneration. While the exact mechanism for the degeneration is
      still not completely understood, neuronal apoptosis and inflammation are thought
      to play roles. We have recently obtained evidence that matrix metalloproteinase
      (MMP)-3 plays a crucial role in the apoptotic signal in DAergic cells as well as
      activation of microglia. The present study tested whether doxycycline might
      modulate MMP-3 and provide neuroprotection of DAergic neurons. Doxycycline
      effectively suppressed the expression of MMP-3 induced in response to cellular
      stress in the DAergic CATH.a cells. This was accompanied by protection of CATH.a
      cells as well as primary cultured mesencephalic DAergic neurons via attenuation
      of apoptosis. The active form of MMP-3, released under the cell stress condition,
      was also decreased in the presence of doxycycline. In addition, doxycycline led
      to downregulation of MMP-3 in microglial BV-2 cells exposed to lipopolysaccharide
      (LPS). This was accompanied by suppression of production of nitric oxide and TNF
      alpha, as well as gene expression of iNOS, TNF-alpha, IL-1beta, and COX-2. In
      vivo, doxycycline provided neuroprotection of the nigral DAergic neurons
      following MPTP treatment, as assessed by tyrosine hydroxylase immunocytochemistry
      and silver staining, and suppressed microglial activation and astrogliosis as
      assessed by Iba-1 and GFAP immunochemistry, respectively. Taken together,
      doxycycline showed neuroprotective effect on DAergic system both in vitro and in
      vivo and this appeared to derive from anti-apoptotic and anti-inflammatory
      mechanisms involving downregulation of MMP-3.

PMID- 19582535
TI  - H-FABP in the early diagnosis of stroke.

PMID- 19582536
TI  - Factors that influence the employment status of people  with multiple sclerosis:
      a multi-national study.
AB  - Paid employment is valuable for society and for the individual. A diagnosis of a
      chronic illness such as multiple sclerosis (MS) can influence a person's
      employment status. Previous studies have reported that demographic and disease
      related aspects can predict whether a person with MS will leave their job. The
      aim of the study was to assess the factors that people with MS believe to
      contribute to their employment status and to determine whether any of these
      differentiate people with MS who are employed from those who are not employed. A
      multinational questionnaire assessed aspects related to employment that
      facilitate or hinder job maintenance. Data was collected in 18 European
      countries. A total of 1,141 questionnaires were completed. Of those responding,
      694 (61%) subjects were employed and 477 (39%) were unemployed. The items that
      significantly differentiated the groups were related to MS symptoms, workplace
      environment and financial considerations. While MS influences employment status
      for many people who face difficult symptoms, aspects like a flexible work
      schedule and financial security are important and perhaps key to promoting job
      maintenance among people with MS.

PMID- 19582537
TI  - A discrepant abduction as an additional characteristic finding in a patient with
      Duane's retraction syndrome.

PMID- 19582538
TI  - [Pacemaker ECG quiz: AV sequential pacing--what is happening?].
AB  - The present case of a 55-year-old patient with heart failure displays a complex
      pacemaker ECG.

PMID- 19582539
TI  - Secular change of the incidence of four fracture types associated with senile
      osteoporosis in Sado, Japan: the results of a 3-year survey.
AB  - We conducted a three-year survey of fracture incidences associated with senile
      osteoporosis--compression fractures of the spine, femoral neck fractures, distal
      radius fractures, and fractures of the proximal end of the humerus--to examine
      secular change. The survey was conducted between 2004 and 2006 on patients in
      Sado City. We calculated the incidence of each fracture based on the population
      of Sado City (per 100,000 person-years). Only clinical or incident fractures were
      diagnosed as new fractures for compression fractures of the spine. Incidence of
      compression fracture of the spine was the highest, followed by femoral neck
      fracture, distal radius fracture, and fracture of the proximal end of the
      humerus. The incidence of femoral neck fracture increased annually from 2004 to
      2006, significantly among the elderly in their 80s (P < 0.05). Compression
      fracture of the spine also increased but not significantly. The incidences of
      distal radius fracture and fracture of the proximal end of the humerus did not
      increase. This increase in incidence of femoral neck fractures associated with
      senile osteoporosis will become an important issue for an aging society such as
      Japan.

PMID- 19582541
TI  - Third-party grooming in a captive chimpanzee group.
AB  - Social grooming is ubiquitous among the captive chimpanzees at Chester Zoo. Seven
      individuals were chosen here for a study of third-party social dynamics. The
      grooming decisions of five adult males were analysed, but only insofar as they
      directed attention to a mother-daughter pair. Uniquely, the daughter was an
      unpopular and physically disabled subadult whose congenital motor impairments
      prevented her from grooming others effectively. The impetus for this study was
      the observation that some males increased their grooming towards the disabled
      daughter during days when the mother had a tumescent anogenital swelling
      (sexually attractive to males) compared to days when the mother was not tumescent
      (less attractive). Apparently, males were grooming the daughter with no
      possibility of payback (because the daughter could never "return the favour"). A
      "grooming rate" (avg. grooming time/hour) was calculated that showed the grooming
      efforts of all five males towards both mother and daughter. These rates were
      compared on days when (1) the mother's anogenital swelling was tumescent, and (2)
      days when the swelling was not tumescent. Each male showed a different pattern of
      behaviour. Two males groomed the daughter significantly more when the mother was
      tumescent. Results for all males were graphed against the quality of the social
      relationship between each male and the mother. Apparently, only males that had a
      weaker relationship to the mother groomed the daughter more when the mother was
      tumescent. This pattern did not exist for males with a stronger relationship to
      the mother. Possibly, the insecure males were using the disabled daughter as a
      way to curry favour with the attractive mother. If this is confirmed, then this
      type of triadic situation is a possible setting for indirect reciprocity to
      occur.

PMID- 19582540
TI  - Mechanical load induces upregulation of transcripts for a set of genes implicated
      in secondary wall formation in the supporting tissue of Arabidopsis thaliana.
AB  - We examined the effects of mechanical load on transcripts of a set of cell wall
      related genes that are implicated in the formation of supporting tissues, by
      applying a 50 mg strip of aluminum foil to the inflorescence stem of Arabidopsis
      thaliana, a weight roughly half the fresh weight of the stem. Transcript levels
      of 12 of the 15 genes examined were increased by load application, as were the
      levels of some transcription factors that regulate secondary wall formation.
      These findings support the involvement of a load-sensing system in regulation of
      supporting tissue formation via transcriptional regulation of cell wall related
      genes.

PMID- 19582542
TI  - Stochastic variation in sex ratios in infant mortality rates due to small samples
      in provisioned Japanese macaque (Macaca fuscata) populations.
AB  - Sex differences in infant mortality in provisioned Japanese macaque populations
      were examined using 10 data sets from five populations. The results indicate that
      there was no available data set in which a sex difference in infant mortality was
      statistically significant. To examine whether the observed sex ratios in infant
      mortality rates could be the product of stochastic variation in small samples, a
      correlation between sample size and the magnitude of sex ratios in infant
      mortality rates was also examined. Notably, the magnitude of sex ratios in infant
      mortality rates declined significantly as sample sizes increased. These results
      suggest that previously reported marked sex ratios in infant mortality could be
      the product of stochastic variation in small samples.

PMID- 19582543
TI  - Low serum secretory immunoglobulin A level and sense of coherence score at an
      early gestational stage as indicators for subsequent threatened premature birth.
AB  - OBJECTIVES: The purpose of this study was to assess the validity of the candidate
      indicators secretory immunoglobulin A (s-IgA) and sense of coherence (SOC) as
      predictors of threatened premature birth. METHODS: This was a panel study
      conducted on women in their first and latter half of pregnancy during survey
      period. The survey period was from December 2005 to June 2006 and from December
      2007 to June 2008. The women enrolled in the study were asked to complete the
      survey questionnaire and provide blood samples for the determinations of
      physiological indicators. The questionnaire consisted of questions related to the
      stress perception scale (SPS), SOC score as an indicator of modifiers of stress,
      demographic data, complications in a previous pregnancy, and the course of the
      current pregnancy. We used s-IgA and high-sensitivity C-reactive protein as a
      physiological stress indicator and a marker of infection, respectively. Seventy
      two eligible subjects were included in the analysis. RESULTS: Twenty-eight
      (38.9%) subjects had undergone treatment for threatened premature birth, and 44
      (61.1%) subjects had not. In the logistic analysis, we set the course of
      pregnancy as a dependent variable, and age, birth history, smoking habits, a
      history of miscarriage, premature birth or threatened premature birth, SPS, SOC,
      and s-IgA in the first half of pregnancy as independent variables. We found that
      low serum s-IgA levels and low SOC scores in the first half of pregnancy were
      associated with threatened premature birth. CONCLUSIONS: Our results suggest that
      low serum s-IgA level and SOC score at an early gestational stage are significant
      indicators for a threatened premature birth.

PMID- 19582544
TI  - Regeneration of 5-HT fibers in hippocampal heterotopia of methylazoxymethanol
      induced micrencephalic rats after neonatal 5,7-DHT injection.
AB  - In order to elucidate the regeneration properties of serotonergic fibers in the
      hippocampus of methylazoxymethanol acetate (MAM)-induced micrencephalic rats (MAM
      rats), we examined serotonergic regeneration in the hippocampus following
      neonatal intracisternal 5,7-dihydroxytryptamine (5,7-DHT) injection. Prenatal
      exposure to MAM resulted in the formation of hippocampal heterotopia in the
      dorsal hippocampus. Immunohistochemical and neurochemical analyses revealed
      hyperinnervation of serotonergic fibers in the hippocampus of MAM rats. After
      neonatal 5,7-DHT injection, most serotonergic fibers in the hippocampus of 2-week
      old MAM rats had degenerated, while a small number of serotonergic fibers in the
      stratum lacunosum-moleculare (SLM) of the hippocampus and in the hilus adjacent
      to the granular cell layer of the dentate gyrus (DG) had not. Regenerating
      serotonergic fibers from the SLM first extended terminals into the hippocampal
      heterotopia, then fibers from the hilus reinnervated the DG and some fibers
      extended to the heterotopia. These findings suggest that the hippocampal
      heterotopia exerts trophic target effects for regenerating serotonergic fibers in
      the developmental period in micrencephalic rats.

PMID- 19582545
TI  - Scanning electron microscopy study of bone intracortical vessels using an
      injection and fractured surfaces technique.
AB  - The intracortical canal/vessel systems of long bones are not yet completely
      understood in terms of their morphology and physiology, mainly because of the
      difficulty of injecting the small calibre vessels and cutting the calcified
      matrix. Here, we apply a novel method combining perfusion of the vessels and
      fracture of the cortical bone to enlighten the architecture of this system. The
      femurs of ten rabbits were perfused with a water-soluble dye (China ink) or
      alcoholic glycerol solution, and the fractured cortex specimens were then
      examined by scanning electron microscopy (SEM). The results document: (1) the
      fibrillar structure of the canal surfaces; (2) the perivascular environment with
      cellular components in different phases of incorporation within the bone matrix;
      (3) previously unreported filamentous structures on the outer surface of vessels,
      which could be interpreted as non-myelinic nerve fibres; (4) the inner
      organisation of the cutting cones. Although based exclusively on morphology,
      these observation have some relevance to increasing knowledge of bone circulation
      physiology in the cortical bone.

PMID- 19582546
TI  - Origin of the 2009 Mexico influenza virus: a comparative phylogenetic analysis of
      the principal external antigens and matrix protein.
AB  - Triple-reassortant swine influenza A (H1) viruses, containing genes from avian,
      human, and swine influenza viruses, emerged and became an outbreak among humans
      worldwide. Over a 1,000 cases were identified within the first month, chiefly in
      Mexico and the United States. Here, the phylogenetic analysis of haemagglutin
      (HA), neuraminidase (NA), and matrix protein (MP) was carried out. The analysis
      showed that the H1 of this reassortant originated from American pigs, while NA
      and MP were more likely from European pigs. All of the 2009 isolates appear
      homogeneous and cluster together, although they are distinct from classical human
      A (H1N1) viruses.

PMID- 19582547
TI  - Chromium effect on ROS generation and detoxification in pea (Pisum sativum) leaf
      chloroplasts.
AB  - Pea plants were exposed to 0, 20, 50, and 100 microM chromium [Cr(VI)] to
      investigate oxidative stress in isolated chloroplasts. Leaf area and biomass
      accumulation were significantly reduced at higher Cr supply. Generation of
      superoxide, hydrogen peroxide, and *OH radical generation was enhanced in the
      chloroplasts isolated from Cr-exposed pea plants. Cr(VI) significantly reduced
      F(v)/F(m) ratio of chlorophyll (Chl) fluorescence, Chl content, and whole chain
      electron transport rate. Superoxide dismutase (SOD) activity increased at lower
      Cr supply while it decreased at higher Cr supply. Ascorbate peroxidase (APX) was
      found to be most sensitive to Cr stress. Monodehydroascorbate reductase activity
      remained higher at 20 and 50 microM Cr but decreased at 100 microM Cr. Increased
      activities of dehydroascorbate reductase (DHAR) and glutathione reductase (GR) in
      the isolated chloroplasts were observed during the initial 3 days of Cr exposure
      of pea plants. Activities of DHAR and GR were increased up to day 3 only.
      Ascorbate and glutathione (GSH) pools showed similar decrease that was more
      evident in the GSH pool as the duration of Cr treatment increased. Observed
      changes in reactive oxygen species concentration, photosynthetic characteristics,
      and antioxidant system indicate that chloroplasts in Cr-exposed pea plants are an
      important target of oxidative stress.

PMID- 19582548
TI  - Generation of reactive oxygen species by beta amyloid fibrils and oligomers
      involves different intra/extracellular pathways.
AB  - A neuropathological characteristic of Alzheimer's disease is the extracellular
      accumulation of amyloid beta peptide (Abeta) in neuritic plaques. Recent
      evidences suggested that soluble Abeta oligomers are the predominant neurotoxic
      species for neurons. Thus, considerable attention has been paid to discriminate
      the cytotoxic pathways of Abeta pre-fibrillar aggregates and mature fibrils. We
      showed that the mechanisms by which Abeta oligomers and fibrils generated
      reactive oxygen species differ in terms of site of production and kinetics,
      suggesting the involvement of different intra/extracellular pathways.

PMID- 19582550
TI  - An ex vivo toe model used to assess applicators for the iontophoretic ungual
      delivery of terbinafine.
AB  - PURPOSE: An ex vivo intact toe model was developed to assess two different
      applicator designs for iontophoretic delivery of terbinafine into the nail only
      or the nail and surrounding skin. METHODS: Iontophoretic permeation studies were
      carried out on intact cadaver toes using nail-only and nail/skin applicators with
      a current dose of 10 mA*min (0.5 mA for 20 min). RESULTS: Iontophoresis enhanced
      drug permeation and tissue loading with both applicators tested. Greater drug
      delivery was observed with the nail/skin applicator due to the additional
      terbinafine being delivered directly through the lower impedance skin area
      surrounding the nail. The concentration of drug loaded into the contact area of
      the nail with the nail-only and nail/skin applicator was ~13 and ~7 fold higher
      than their respective passive delivery levels but equivalent from each other in
      total drug mass delivered over the whole nail plate. In vitro release of drug
      from the iontophoretically loaded nails into agar suggests that a single
      treatment could have a prolonged effect (>50 days). CONCLUSIONS: This study
      demonstrates that the ex vivo toe model was useful in assessing the functionality
      of the different applicator designs. These results suggest that iontophoresis can
      significantly enhance the delivery of drugs to both the hard and soft tissues of
      the toe for the treatment of onychomycosis and other nail disorders.

PMID- 19582549
TI  - The Ca2+-independent PKC (p105) mediates the PMA-activation of marine mussel
      hemocytes and the Ca2+-dependent PKC (p60) does not intervene.
AB  - Previous works revealed the presence of a Ca(2+)-dependent protein kinase (p60)
      and a Ca(2+)-independent protein kinase (p105) in the mantle tissue from the sea
      mussel Mytilus galloprovincialis Lmk. The expression of both isoforms shows a
      balance between cytosolic and membrane fractions in mantle, gills, and
      hepatopancreas, whereas, in hemocytes, their expression is mainly cytosolic, as
      happens in muscle tissues with p60 alone. Both enzymatic forms contain
      phosphorylated serines, and no phosphorylation was detected in tyrosines. Only
      the form p105 mediates the PMA-induced activation of the hemocytes of M.
      galloprovincialis, and it does so by a process of down-regulation. The form p60
      does not respond to the presence of the phorbol ester, suggesting structural
      differences related to the binding sites of the diacylglycerol.

PMID- 19582551
TI  - Stabilization of peptide vesicles by introducing inter-peptide disulfide bonds.
AB  - PURPOSE: Previously, we have shown that the amphiphilic oligopeptide SA2 (Ac-Ala
      Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) spontaneously self-assemble into nano
      sized vesicles in aqueous environment. Relative weak individual intermolecular
      interactions dominate such oligopeptide assemblies. In this study we aimed at
      improving the stability of such peptide vesicles by covalently crosslinking the
      oligopeptide vesicles using disulfide bonds. Two and three cysteines were
      introduced in the SA2 peptide sequence to allow crosslinking (Ac-Ala-Cys-Val-Cys
      Leu-(Leu/Cys)-Leu-Trp-Glu-Glu-COOH). RESULTS: Upon disulfide formation the
      crosslinked vesicles remained stable under conditions that disrupted the non
      crosslinked peptide vesicles. The stabilized vesicles were more closely examined
      in terms of particle size (distribution) using atomic force microscopy, cryogenic
      electron microscopy, as well as dynamic light scattering analysis, showing an
      average particle radius in number between 15 and 20 nm. Using entrapment of
      calcein it was shown that intermolecular crosslinking of peptides within the
      vesicles did not affect the permeability for calcein. CONCLUSION: Introduction of
      cysteines into the hydrophobic domain of the SA2 amphiphilic oligopeptides is a
      feasible strategy for crosslinking the peptide vesicles. Such small crosslinked
      oligopeptide vesicles may hold promise for drug delivery applications.

PMID- 19582552
TI  - Facilitating empowerment in employees with chronic disease: qualitative analysis
      of the process of change.
AB  - INTRODUCTION: In the field of healthcare, empowering patients who have a chronic
      disease is defined as increasing their knowledge and skills, in order to enable
      them to define their treatment goals and take personal responsibility for their
      medical treatment. Our goal was to explore the nature of empowerment for
      employees who have a chronic disease and who experience work-related problems.
      METHODS: We used an explorative qualitative approach to document, from a
      professional perspective, the experiences of patients who participated in an
      empowerment training program. The researcher and the three instructors identified
      several themes which appeared to be important to many participants. These themes
      were fine-tuned and illustrated using brief case histories. RESULTS: We
      identified seven themes and characterized them in terms of employee tasks. These
      included: (1) developing a realistic understanding of one's abilities, (2)
      standing up for oneself in a self-confident way, (3) maintaining social relations
      based on mutual understanding with supervisors and colleagues, (4) collecting and
      assimilating knowledge of one's options, rights and duties, (5) consulting others
      and negotiating with regard to work accommodations, (6) planning one's job so as
      to provide personal satisfaction, and (7) maintaining a social life outside work.
      Not every employee is faced with all of these tasks, but most have to deal with
      several. CONCLUSION: Empowerment presupposes that employees with a chronic
      disease can act to solve problems at the workplace. The experiences during a
      comprehensive empowerment training illustrate that a process of reflection on
      personal emotions and a cognitive process of exploration and identification of
      bottlenecks at work may precede these actions. Our primary contribution is the
      aforementioned list of seven common tasks that many workers have to perform.
      Disseminating the list can support employees who have a chronic disease and may
      also be useful for their managers, HRM staff, occupational health and other
      healthcare workers.

PMID- 19582553
TI  - A comparison of ambient casino sound and music: effects on dissociation and on
      perceptions of elapsed time while playing slot machines.
AB  - This research examined the effects of a casino's auditory character on estimates
      of elapsed time while gambling. More specifically, this study varied whether the
      sound heard while gambling was ambient casino sound alone or ambient casino sound
      accompanied by music. The tempo and volume of both the music and ambient sound
      were varied to manipulate temporal engagement and introspection. One hundred and
      sixty (males = 91) individuals played slot machines in groups of 5-8, after which
      they provided estimates of elapsed time. The findings showed that the typical
      ambient casino auditive environment, which characterizes the majority of gaming
      venues, promotes understated estimates of elapsed duration of play. In contrast,
      when music is introduced into the ambient casino environment, it appears to
      provide a cue of interval from which players can more accurately reconstruct
      elapsed duration of play. This is particularly the case when the tempo of the
      music is slow and the volume is high. Moreover, the confidence with which time
      estimates are held (as reflected by latency of response) is higher in an auditive
      environment with music than in an environment that is comprised of ambient casino
      sounds alone. Implications for casino management are discussed.

PMID- 19582554
TI  - I am not a lucky person: an examination of the dimensionality of beliefs about
      chance.
AB  - The purpose of this article was to verify whether beliefs about chance are multi
      or unidimensional constructs. Traditionally, authors who assessed beliefs about
      chance postulated that individuals who perceive themselves as unlucky usually
      believe that chance is random and are less confident as well as more anxious.
      Curiously, it appears that sometimes these individuals act as if they were
      motivated to avoid negative consequences. In order to better understand these
      puzzling findings, two studies were performed to compare three instruments
      intended to assess beliefs about chance and to verify their causal properties. In
      total, 285 students filled out a battery of instruments, including chance
      questionnaires (LOC, BIGL and MBIC) and personality traits. Overall, results
      showed that luck, through perceived controllability, seems to be related to
      volitional control, whereas chance, which is more stable and less controllable
      than luck, can be associated with cognitive distortions. The implications of
      these results are discussed.

PMID- 19582555
TI  - Electronic gaming machine gambling: measuring motivation.
AB  - Electronic gambling machines (EGMs) are known to be a particularly risky form of
      gambling (Petry. Addiction 98(5):645-655, 2003). It is vital that researchers and
      clinicians are aware of factors which could lead to people having problems with
      this form. Gambling motivation is one such factor. This study developed a measure
      of EGM gambling motivations based on the results of qualitative research
      conducted with EGM problem gamblers and experienced counsellors (Thomas et al.
      Int J Mental Health Addiction 7:97-107, 2009). A community based sample of 232
      females (M = 29.60 years of age, SD = 15.41 years) and 123 males (M = 29.64 years
      of age, SD = 12.29 years) participated. Exploratory factor analysis extracted
      three motivational factors indicating people gambled on EGMs to escape, for its
      accessibility and for the social environment. Gambling to escape and for its
      accessibility had substantial positive correlations with frequency of EGM
      gambling and gambling problems. Social environment correlated less well with
      these indicators of excessive gambling. Correlations between factors suggested
      the accessible, social experience offered by EGM venues increases their appeal as
      a means of escape. The new subscales were internally consistent and demonstrated
      good evidence of validity. This new measure will facilitate future investigations
      into the relationships between gambling motivations, other aetiological factors
      and EGM problem gambling.

PMID- 19582556
TI  - Impact of visiting an Onsite Casino information centre on perceptions about
      randomness and gambling behaviours.
AB  - At the beginning of 2000, some educational initiatives in the field of
      responsible gambling resulted in the implementation of Onsite Casino Information
      Centres (OCICs). However, no study has yet empirically evaluated the impact of
      visiting an OCIC. This paper includes two studies evaluating the OCIC Au Centre
      du Hasard, located in Montreal, Quebec. The goal of the first study was to
      identify the profile of the visitors and to assess their appreciation. After a
      visit, 336 patrons accepted to complete a pen and paper questionnaire. The goal
      of the second study was to evaluate the impact of a visit on the perceptions
      about randomness and the gambling behaviours of the visitors. For this study, 67
      visitors were evaluated before, after, and 3 months following a visit and their
      results were compared to a control group. Data showed that most visitors were
      seniors, occasional slot machine gamblers, and in control of their gambling
      activities. The majority of guests greatly appreciated their visit. A visit to Au
      Centre du Hasard seemed to modify the misconceptions towards the notion of
      randomness but not the gambling behaviours. These gains were maintained at 3
      month follow-up. Results with respect to other prevention programs are discussed,
      and future research avenues are suggested.

PMID- 19582557
TI  - Affect-regulation expectancies among Gamblers.
AB  - Factor scores on a gambling expectancy questionnaire (GEQ) were used to subtype
      132 university students who gamble regularly (37.9% male; M age = 22.6 years, SD
      = 6.04) as: Reward Expectancy Gamblers (Reward EGs)-have strong expectations that
      gambling augments positive mood, Relief Expectancy Gamblers (Relief EGs)-have
      strong expectations that gambling relieves negative affect, and Non-Expectancy
      Gamblers (Non-EGs)-have neither strong expectation. Gambling on a high-low card
      game was compared across subtypes following priming for either "relief" or
      "reward" affect-regulation expectancies with the Scrambled Sentence Test (SST).
      The hypothesized Prime type x GEQ subtype interaction was not significant. When a
      more stringent set of criteria for GEQ subtyping was imposed, the "purified" sub
      sample (n = 54) resulted in the hypothesized statistically significant Prime type
      x GEQ subtype interaction. Relief EGs gambled more after being primed with the
      construct "relief of negative emotions" compared to after being primed with the
      construct "augmentation of positive emotion." Planned orthogonal contrasts showed
      a significant linear increase in number of bets made across GEQ subtypes when
      prime type corresponded to GEQ subtype. The results suggest a need for components
      in gambling treatment programs that address clients' expectancies that gambling
      can provide a specific desirable emotional outcome.

PMID- 19582558
TI  - Elucidating anomalous protein diffusion in living cells with fluorescence
      correlation spectroscopy-facts and pitfalls.
AB  - Anomalous protein diffusion has been frequently observed in intracellular fluids
      and on membranes of living cells. Indeed, a large variety of specimen, from
      bacteriae to mammalian cells, and several non-invasive measurement techniques,
      e.g. fluorescence correlation spectroscopy, have revealed that the mean square
      displacement (MSD) of proteins in vivo is often characterized by an anomalous
      power-law increase mean value of tau(t)(2) mean value of ~ t(alpha) with 0.5 <
      alpha </= 0.8. Here, we review these results with a particular focus on
      fluorescence correlation spectroscopy, and we report on possible causes of
      variations of the anomaly degree alpha. Moreover, we highlight generic
      consequences of anomalous diffusion that are likely to play an important role in
      the cellular context.

PMID- 19582559
TI  - Studying the interaction of pirarubicin with DNA and determining pirarubicin in
      human urine samples: combining excitation-emission fluorescence matrices with
      second-order calibration methods.
AB  - In this paper, UV-vis spectroscopy and fluorescence were combined to study the
      binding of Calf thymus DNA (ct-DNA) with the anthacycline antibiotic drug
      pirarubicin (THP). Ethidium bromide (EB) as the fluorescence probe was used to
      study the competitive binding interactions of THP with DNA by excitation-emission
      fluorescence matrices (EEFMs) coupled with the parallel factor analysis (PARAFAC)
      and the alternating normalization-weighted error algorithm (ANWE) with the second
      order advantage. All the results conformed that THP mainly bound with DNA by
      intercalation. Meanwhile, the two second-order calibration methods have been
      successfully applied to quantify THP in urine samples. Figures of merit were
      applied to compare the performance of the two methods. The results presented in
      this work showed that both the PARAFAC and ANWE methods were the convincing way
      to be applied in the complex biological systems even in the presence of
      uncalibrated interferences.

PMID- 19582560
TI  - How racial and ethnic groupings may mask disparities: the importance of
      separating Pacific Islanders from Asians in prenatal care data.
AB  - OBJECTIVE: To understand racial/ethnic differences in prenatal care receipt among
      Pacific Islanders and Asians, who are often combined into a single A/PI category.
      METHODS: Retrospective, population-based data were collected by the Vital
      Statistics branch of the California Department of Health Services. Approximately
      2.6 million records of all live California births with a birth certificate in
      2000-2004 were included. Analysis focused on prenatal care receipt and population
      characteristics associated with lack of adequate prenatal care, especially among
      Asian and Pacific Islander groups. RESULTS: Pacific Islanders (n = 11,962) were
      the most likely, compared to any other racial/ethnic group, to have inadequate
      prenatal care (OR = 2.9, 95% CIs 2.8-3.1), even when controlling for factors
      known to affect care receipt, specifically maternal age, educational attainment,
      parity, insurance, geographical region of residence, and maternal place of birth.
      In contrast, Asian women (n = 295,741) received care closer to that of the White
      reference group (OR = 1.5, 95% CIs 1.5-1.5). Among Pacific Islanders, Samoans (OR
      = 3.0, 95% CIs 2.7-3.4) were at particular risk of inadequate care compared to
      other PI sub-groups. CONCLUSION: Pacific Islander women received less adequate
      prenatal care than women of other racial/ethnic groups. The common practice of
      combining Asians and Pacific Islanders into a single A/PI category may mask needs
      in the Pacific Islander community. Therefore, in order to continue to reduce
      health disparities, it may be necessary to collect separate data on these two
      distinct populations in order to be able to appropriately direct programs and
      resources.

PMID- 19582561
TI  - Are you what your mother weighs? Evaluating the impact of maternal weight
      trajectories on youth overweight.
AB  - In this study, we investigate how three alternative measures of maternal body
      mass index (BMI) relate to youth overweight. We contrast the typical cross
      sectional measure of maternal BMI with a longitudinal mean and a standard
      deviation in maternal BMI. Using National Longitudinal Survey of Youth data, we
      estimate logistic regressions that relate maternal BMI to the risk of a youth
      being overweight while controlling for other familial characteristics.
      Participants in this study are 918 males and 841 females who were age 16-21 and
      either healthy weight or overweight in 2006. To be eligible for inclusion, teens
      were 15 years old by December 2006. After comparing several measures of maternal
      weight, we find that higher mean maternal BMI measured over the life of the
      adolescent has the strongest relationship with the odds of youth overweight for
      both male and female adolescents. For boys, a one unit increase in mother's mean
      BMI increases the odds of being overweight by 16% (OR = 1.16, 95% CI 1.11-1.20)
      while for girls the increase in the odds of being overweight is 13% (OR = 1.13,
      95% CI 1.09-1.18). Our findings suggest that researchers should move beyond
      static measures of maternal weight when examining the correlates of youth BMI.
      Maternal weight histories offer additional insights about the youth's home
      environment that are associated with the risk of a youth being overweight.

PMID- 19582562
TI  - The analysis of tryptase in serum of sarcoidosis patients.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized
      by activation of macrophages and T lymphocytes. Relatively little is known about
      the role of mast cells and their mediators in the pathogenesis of sarcoidosis.
      Tryptase is an enzyme produced by activated mast cells, regarded as a marker of
      mast cell activation. To analyse tryptase concentrations in serum of sarcoidosis
      patients in an attempt to define the role of tryptase and mast cells in the
      pathogenesis of sarcoidosis and to evaluate the potential of tryptase as marker
      of disease severity. Quantitative analysis of tryptase concentrations was
      performed in serum of patients with stable sarcoidosis (n = 12), progressive
      sarcoidosis (n = 23) and controls (n = 13). Patients enrolled in the study had
      been monitored at Siena Regional Referral Centre for Sarcoidosis from onset for
      at least 12 months. Significantly higher concentrations of tryptase were found in
      peripheral blood of sarcoidosis patients (6.08 +/- 3.98 microg/l) than controls
      (2.96 +/- 1.75microg/l; p = 0.012). Patients with progressive disease showed the
      highest tryptase concentrations in serum. Tryptase and mast cells may be involved
      in the immunopathogenesis of sarcoidosis and further studies are required to
      understand if tryptase may represent a marker of sarcoidosis severity.

PMID- 19582563
TI  - Sex differences in autism spectrum disorder: an examination of developmental
      functioning, autistic symptoms, and coexisting behavior problems in toddlers.
AB  - Little is known about the female presentation of autism spectrum disorder (ASD)
      during early childhood. We investigated sex differences in developmental profiles
      using the Mullen Scales of Early Learning, autistic symptoms on the ADOS-G, and
      coexisting behavior problems on the CBCL in 157 boys and 42 girls with ASD aged
      1.5-3.9 years. Overall, boys and girls evidenced a markedly similar pattern of
      developmental profiles, autism symptoms, and coexisting behavior problems,
      although subtle differences exist. Boys and girls evidenced a similar pattern of
      developmental strengths and weaknesses. Girls with ASD evidenced greater
      communication deficits than boys and boys evidenced more restricted, repetitive,
      and stereotyped behavior than girls. Girls exhibited more sleep problems and
      anxious or depressed affect than boys.

PMID- 19582564
TI  - Dissemination of evidence-based practice: can we train therapists from a
      distance?
AB  - Although knowledge about the efficacy of behavioral interventions for children
      with ASD is increasing, studies of effectiveness and transportability to
      community settings are needed. The current study conducted an effectiveness trial
      to compare distance learning vs. live instruction for training community-based
      therapists to implement the Early Start Denver Model. Findings revealed: (a)
      distance learning and live instruction were equally effective for teaching
      therapists to both implement the model and to train parents; (b) didactic
      workshops and team supervision were required to improve therapists' skill use;
      (c) significant child gains occurred over time and across teaching modalities;
      and (d) parents implemented the model more skillfully after coaching.
      Implications are discussed in relation to the economic and clinical utility of
      distance learning.

PMID- 19582566
TI  - Quantitative architectural analysis: a new approach to cortical mapping.
AB  - Results from functional imaging studies are often still interpreted using the
      classical architectonic brain maps of Brodmann and his successors. One obvious
      weakness in traditional, architectural mapping is the subjective nature of
      localizing borders between cortical areas by means of a purely visual,
      microscopical examination of histological specimens. To overcome this limitation,
      objective mapping procedures based on quantitative cytoarchitecture have been
      generated. As a result, new maps for various species including man were
      established. In our contribution, principles of quantitative cytoarchitecture and
      algorithm-based cortical mapping are described for a cytoarchitectural
      parcellation of the human auditory cortex. Defining cortical borders based on
      quantified changes in cortical lamination is the decisive step towards a novel,
      highly improved probabilistic brain atlas.

PMID- 19582567
TI  - Impact of the interaction between the 5HTTLPR polymorphism and maltreatment on
      adolescent depression. A population-based study.
AB  - Serotonin plays a central role in mood regulation and the development of
      depressive disorders. The present study investigated whether a functional
      polymorphism (5HTTLPR) of the serotonin transporter gene interacts with
      maltreatment in the prediction of depression. A cohort of 17-18 years old
      students (n = 1,482) anonymously completed the Survey of Adolescent Life and
      Health in Vestmanland 2006 and gave a saliva sample for DNA extraction. An
      association between maltreatment and adolescent depression was found independent
      of sex. When the whole population was analyzed, no main effect of 5HTTLPR in
      association with depression was found. When separated by sex, a significant main
      effect and a G x E interaction effect of the SS allele was found among girls. No
      gene main effect or G x E interaction effect was found among boys. The present
      study confirms previous findings of sex differences in interaction effects
      between the 5HTTLPR polymorphism and maltreatment in the prediction of adolescent
      depression.

PMID- 19582565
TI  - Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with
      anxiety, ADHD and tics in children with autism spectrum disorder.
AB  - The aim of the study is to examine rs4680 (COMT) and rs6265 (BDNF) as genetic
      markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV
      referenced rating scale for a total sample of 67 children with autism spectrum
      disorder (ASD). Both COMT (p = 0.06) and BDNF (p = 0.07) genotypes were
      marginally significant for teacher ratings of social phobia (etap (2) = 0.06).
      Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p =
      0.01, etap (2) = 0.10) and teacher-rated tics (p = 0.04; etap (2) = 0.07). There
      was also evidence of a possible interaction (p = 0.02, etap (2) = 0.09) of BDNF
      genotype with DAT1 3' VNTR with tic severity. BDNF and COMT may be biomarkers for
      phenotypic variation in ASD, but these preliminary findings remain tentative
      pending replication with larger, independent samples.

PMID- 19582568
TI  - Evaluating Project Connect: improving juvenile probationers' mental health and
      substance use service access.
AB  - Project Connect is a multilayered county-specific program aimed at linking
      juvenile probationers to needed mental health and substance use services. In four
      NY counties, the intervention included cooperative agreements between probation
      and mental health authorities, program materials to facilitate referral, in
      service training for probation officers, and systematic screening for mental
      health needs. Charts for 583 Baseline youths were reviewed and compared with 594
      youths undergoing intake under Project Connect. Compared to Baseline, under
      Project Connect, referred youths were 2.7 times as likely to access services,
      regardless of youth or county characteristics, service availability, or when the
      intervention took place.

PMID- 19582569
TI  - Co-administration of monosialoganglioside and skeletal muscle cells on dorsal
      root ganglion neuronal phenotypes in vitro.
AB  - The neuropeptide-immunoreactive (IR) and neurofilament-IR neurons are two major
      phenotypical classes in dorsal root ganglion (DRG). Targets of neuronal
      innervation play a vital role in regulating the survival and differentiation of
      innervating neurotrophin-responsive neurons. Monosialoganglioside (GM1) has been
      considered to have a neurotrophic factor-like activity. Both GM1 and target
      skeletal muscle (SKM) cells are essential for the maintenance of the function of
      neurons. However, whether target SKM cells and GM1, alone or associated, generate
      neuropeptide or neurofilament expression remains unclear. The aim of the present
      study is to investigate the effects of GM1 or/and SKM on DRG neuronal phenotypes.
      DRG neurons containing the neuropeptide substance P (SP) and neurofilament 200
      (NF-200) were quantified using immunofluorescent labeling in cultures of DRG,
      which was dissected out at times before (at embryonic days 12.5, E12.5) and after
      (at E19.5) sensory neurons contact peripheral targets in vivo. DRG neurons were
      cultured in absence or presence of GM1 or/and SKM cells. In this experiment, we
      found that: (1) GM1 promoted expression of SP and NF-200 in E12.5 DRG cultures;
      (2) SKM cells promoted expression of NF-200 but not SP in E12.5 DRG cultures; (3)
      GM1 and target SKM cells had additive effects on expression of SP and NF-200 in
      E12.5 DRG cultures; and (4) SKM or/and GM1 did not have effects on expression of
      SP and NF-200 in E19.5 DRG cultures. These results suggested that GM1 could
      influence DRG, two major neuronal phenotypes, before sensory neurons contact
      peripheral targets in vivo. Target SKM cells could only influence neurofilament
      expressed neuronal phenotype before sensory neurons contact peripheral targets in
      vivo. GM1 and SKM cells had the additive effects on two major DRG neuronal
      classes, which express neuropeptide or neurofilament when DRG cells were
      harvested before sensory neurons contact peripheral targets in vivo. These
      results offered new clues for a better understanding of the association of GM1
      or/and SKM with neuronal phenotypes.

PMID- 19582571
TI  - Development and application of a system for seminolipid metabolism using mouse
      seminiferous tubules.
AB  - A convenient tool for studying metabolism of seminolipid in testis was developed
      by using mouse isolated seminiferous tubules prepared by collagenase treatment.
      Because more than 99% of [(35)S]sulfate-incorporation was distributed in
      seminolipid, its metabolism in seminiferous tubules can be analyzed without
      disturbance of the other sulfolipids in this assay system. Furthermore, the
      contents of seminolipid and its precursor, galactosylalkylacylglycerol, which
      were determined by liquid chromatography-electrospray ionization mass
      spectrometry, did not change within a few hours, indicating that the
      incorporations of [(35)S]sulfate into seminolipid solely reflects the turnover
      rate of this sulfolipid. As an initial application of this system, we
      characterized heat-susceptibility of the seminolipid turnover rate in mouse
      seminiferous tubules. Severe heating (44 degrees C for 10 min) of the isolated
      seminiferous tubules suppressed the (35)S-incorporation into seminolipid to 47%
      of heating at scrotal temperature (32 degrees C for 70 min). In contrast,
      pretreatment of the testis in vivo under the same condition (44 degrees C for 10
      min) did not decrease the seminolipid turnover rate in the isolated seminiferous
      tubules. In addition, the activity of galactocerebroside sulfotransferase
      decreased in the temperature-dependent manner in seminiferous tubules as well as
      crude tubular homogenates, where the activity is significantly more stable in the
      former than the latter. The newly developed system could provide useful basic
      data for further analyses of seminolipid metabolism in the testis.

PMID- 19582570
TI  - Metabolic characterization of a mouse deficient in all known leptin receptor
      isoforms.
AB  - We have characterized a newly generated mouse model of obesity, a mouse strain
      deficient in all five previously described leptin receptor isoforms. These
      transgenic mice, named the db (333)/db (333) mice, were identified from an ENU
      mutagenesis screen and carry a point mutation in the seventh exon of the db gene
      encoding the leptin receptor, resulting in a premature stop codon (Y(333)Stop)
      and gene product that lacks STAT signaling domains. db (333)/db (333) mice have a
      morbidly obese phenotype, with body weights diverging from wild type as early as
      4 weeks of age (P < 0.05). To determine the contribution of the short isoforms of
      the leptin receptor in this metabolic phenotype, we performed an extensive
      metabolic characterization of the db (333)/db (333) mouse in relation to the well
      characterized db/db mouse lacking only the long form of the leptin receptor. db
      (333)/db (333) mice have similar endocrine and metabolic parameters as previously
      described in other leptin receptor transgenic mice including db/db mice that lack
      only the long isoform of the leptin receptor. However, db (333)/db (333) mice
      show a subtle trend toward higher body weight and insulin levels, lower oxygen,
      carbon dioxide production, respiratory exchange ratio (RER), and temperature than
      db/db mice suggesting the short isoforms may play an additional role in energy
      homeostasis.

PMID- 19582572
TI  - The effects of hypoxia/reoxygenation on the physiological behaviour of U373-MG
      astrocytes.
AB  - Nerve cells are very susceptible to hypoxia responsive for mitochondrial
      dysfunctions involved in the subsequent oxidative stress, apoptosis and necrosis.
      In this paper, we examined the effect of 12 h incubation of U-373 MG astrocytes
      in hypoxic environment (73% N(2): 2% O(2): 5% CO(2), v:v) by evaluating cell
      proliferation, modifications of NO and ATP production, intracellular Ca(2+)
      concentration [Ca(2+)](i), membrane potential, desferoxamine-chelatable free
      iron, esterified F2-isoprostanes levels and the production of phosphorylated ERK.
      The same parameters were evaluated also after a following re-oxygenation period
      of 24 h. Immediately after hypoxia the NO concentration increased significantly
      and returned to values similar to those of controls after the re-oxygenation
      period. At the same time, ATP levels remained similar to controls and the cell
      proliferation significantly decreased. This involved a significant increase of
      [Ca(2+)](i) immediately after hypoxia and the value remained significantly
      elevated after the following re-oxygenation period. Moreover, after hypoxia,
      astrocytes were slightly although not significantly depolarized. Indeed iron and
      F2-isoprostanes levels increased significantly after hypoxia. Finally ERK
      proteins increased slowly and not significantly after hypoxia and the same trend
      was observed after the re-oxygenation period. On the whole, our results indicate
      that 2% O(2) hypoxia induces a moderate oxidative stress, well tolerated by U-373
      MG cells, remaining the ATP production, mitochondrial membrane potential and
      activated ERK proteins, similar to the values of controls.

PMID- 19582573
TI  - Satisfaction with mental health services in a Latin American community of carers
      of patients with schizophrenia.
AB  - The aim of this study is to compare levels of satisfaction with Mental Health
      Services in a sample of 41 relatives of patients with schizophrenia, users of the
      Mental Health Public Service in the city of Arica, Chile. Of this sample, 18
      participated in a group family intervention and 23 did not. Overall, the total
      sample of relatives expressed satisfaction with the Mental Health Service.
      However, in the compound satisfaction measure (patient's evolution and
      satisfaction with the mental health service), there were significant differences
      between caregivers who participated in the psycho-educative multifamily
      intervention and those who did not. The control group was more satisfied with the
      care provided by mental health services. The experimental group reported greater
      satisfaction in the area of patient's evolution. This result is of special
      interest since it indicates that psycho-educational programs increase relatives'
      satisfaction with the patient's evolution and also has positive consequences for
      the relationship between patients and their relatives.

PMID- 19582574
TI  - Psychometric properties of an assessment for mental health recovery programs.
AB  - The concept of recovery can be operationalized from either the point of view of
      the consumer, or from the perspective of the agency providing services. The
      Milestones of Recovery Scale (MORS) was created to capture aspects of recovery
      from the agency perspective. Evidence establishing the psychometric properties of
      the MORS was obtained in three efforts: Inter-rater reliability using staff at
      The Village, a multi-service organization serving the homeless mentally ill in
      Long Beach, California; inter-rater reliability was also obtained from Vinfen
      Corporation, a large provider of housing services to mentally ill persons in
      Boston, Massachusetts. A test-retest reliability study was conducted using staff
      rating of clients at The Village, and evidence for validity was obtained using
      the Level of Care Utilization System (LOCUS) as a validity measure. The intra
      class correlation coefficient for the inter-rater reliability study was r = .85
      (CI .81, .89) for The Village and r = .86 (CI .80, .90) for Vinfen Corporation;
      test-retest reliability was r = .85 (CI .81, .87); and validity coefficients for
      the LOCUS were at or above r = .49 for all subscales except one. There is
      sufficient evidence for the reliability and validity of the MORS.

PMID- 19582575
TI  - HER-2/neu and topoisomerase-II-alpha expression and genic amplification in
      pancreatic adenocarcinoma.

PMID- 19582576
TI  - Diversion colitis in a 19-year-old female with megacystis-microcolon-intestinal
      hypoperistalsis syndrome.

PMID- 19582577
TI  - Patient self-administered abdominal pressure to reduce loop formation during
      minimally sedated colonoscopy.
AB  - CONTEXT: Assistant-administered abdominal pressure is usually required to reduce
      loop formation during a colonoscopy. The effect of patient self-administered
      abdominal pressure has not been evaluated. OBJECTIVE: To compare the
      effectiveness of patient self-administered abdominal pressure with assistant
      administered abdominal pressure to reduce loop formation during colonoscopy
      performed with minimal sedation. PATIENTS: Consecutive patients who underwent
      colonoscopy were randomized to receive either patient self-administered abdominal
      pressure (patient group, n = 51) or assistant-administered abdominal pressure
      (assistant group, n = 52) when looping occurred during colonoscopy minimally
      sedated with meperidine. When patient-administered abdominal pressure failed to
      reduce the loop formation, an assistant took over and delivered the abdominal
      pressure. RESULTS: No difference was found regarding cecal intubation rate,
      intubation time, mean pain scores, and overall satisfaction of patients between
      groups. However, fewer patients required assistant-administered pressure in the
      patient group than in the assistant group (18/51 vs. 41/52, P < 0.001).
      CONCLUSIONS: Patient self-administered pressure is effective in reducing looping
      during minimally sedated colonoscopy.

PMID- 19582578
TI  - Expression of urotensin II and its receptor in human liver cirrhosis and
      fulminant hepatic failure.
AB  - OBJECTIVES: Urotensin II [U-II] plasma levels are increased in liver cirrhosis
      [LC] and are discussed as an important mediator of portal hypertension since the
      U-II antagonist palosuran has beneficial effects on portal hypertension by
      increasing splanchnic resistance. Nevertheless, no data are available on the
      intrahepatic expression of U-II and its receptor [UT] in humans. METHODS: U-II
      and UT expression were analyzed in the livers of patients with LC, fulminant
      hepatic failure [FHF], and normal controls [NC] using immunohistochemistry.
      RESULTS: Both U-II and UT were expressed in the liver on endothelial cells from
      arteries, veins, and bile ducts as well as on Kupffer cells. In LC, the total
      number of U-II-expressing cells was 20% lower compared to NC (P < 0.001), while
      expression of UT did not differ between LC and NC. In contrast, significant
      enhanced number of U-II and UT positive cells were found in FHF compared to LC
      and NC (P < 0.001). U-II and UT expression was also found in portal veins,
      without differences between LC and NC. CONCLUSIONS: Our data demonstrate that U
      II and UT are not elevated in human cirrhotic livers but are in livers of
      patients with FHF.

PMID- 19582579
TI  - Long-term quality of life improvement in subjects with healed erosive
      esophagitis: treatment with lansoprazole.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic symptomatic
      condition and may be associated with erosive esophagitis (EE). Considerable data
      on the long-term maintenance of healing of EE are available, but data on long
      term GERD symptom prevention and patient quality of life (QOL) are limited. AIMS:
      To investigate QOL in subjects with healed EE who received 12 months of double
      blind maintenance treatment with lansoprazole or ranitidine, followed by long
      term open-label lansoprazole therapy to prevent recurrence of EE. METHODS:
      Subjects with healed EE received 12 months of double-blind maintenance treatment
      with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by
      dose-titrated, open-label lansoprazole therapy for up to 82 months. RESULTS:
      During double-blind treatment (n = 206), lansoprazole-treated patients showed
      significantly (P <or= 0.05) greater improvements than ranitidine-treated patients
      in the frequency, severity, and 'bothersomeness' of heartburn, the symptom index,
      problems of activity limitation, eating and drinking problems, symptom problems,
      health distress, and social functioning. During dose-titrated, open-label
      treatment (n = 195), all disease-specific QOL scales except sleep improved
      significantly (P < 0.001) from open-label baseline at each time-point.
      CONCLUSIONS: Maintenance treatment with lansoprazole for 12 months in healed EE
      subjects produced significantly greater improvements in QOL indicators than
      ranitidine. These improvements were sustained during dose-titrated, open-label
      lansoprazole treatment.

PMID- 19582580
TI  - Non-invasive testing for Helicobacter pylori in patients hospitalized with peptic
      ulcer hemorrhage: a cost-effectiveness analysis.
AB  - PURPOSE: Guidelines recommend routine invasive screening for Helicobacter pylori
      in patients with peptic ulcer hemorrhage (PUH). However, compliance with
      screening remains suboptimal. The aim of this study was to determine if a
      simplified approach based on noninvasive screening is cost effective in PUH.
      RESULTS: In the base case, post-endoscopy urea breath test (UBT) dominated the
      invasive testing with 34 fewer hemorrhages and cost savings of $406,600 in a
      cohort of 10,000 patients. When compliance with invasive testing decreases to
      60%, post-endoscopy UBT leads to 109 fewer hemorrhages and cost savings of
      $1,089,600. The invasive strategy becomes the preferred choice if the sensitivity
      of UBT reduces to <75%, such as in patients taking proton-pump inhibitors (PPI)
      before hospitalization. CONCLUSIONS: Post-endoscopy UBT is cost effective in PPI
      naive patients presenting with PUH. This strategy, once prospectively validated,
      can prove to be a preferred approach in institutions where compliance with
      invasive testing is suboptimal.

PMID- 19582581
TI  - Socio-demographic variability in adolescent substance use: mediation by parents
      and peers.
AB  - The current study examined socio-demographic variability in adolescent substance
      use and the mediating roles of maternal knowledge, paternal knowledge and peer
      substance use. The data were obtained from the United States records (N = 8,795)
      of the Health Behavior in School-Aged Children 2005/2006 Survey, in grades 6
      through 10. The analyses employed multiple indicator multiple cause and
      structural equation models. Adolescent substance use was measured by frequencies
      of alcohol use, being drunk, and cigarette and marijuana use in the past month.
      Peer influence had a direct influence on adolescent substance use. Maternal
      knowledge had both direct and indirect influences on adolescent substance use
      through its negative association with substance-using peers, whereas paternal
      knowledge only had an indirect influence. Parental knowledge and peer substance
      use totally mediated differences in adolescent substance use by grade;
      differences between Caucasian and African-American or Hispanic adolescents; and
      differences between adolescents from two-parent families and those from single
      mother, single-father or mother-stepfather families. Parental knowledge and peer
      substance were important mediators which largely accounted for variability in the
      prevalence of adolescent substance use by grade, race/ethnicity, and family
      structure.

PMID- 19582582
TI  - Undocumented migrants in Switzerland: geographical origin versus legal status as
      risk factor for tuberculosis.
AB  - Undocumented migrants, meaning migrants without a legal residency permit, come to
      Geneva from countries with high tuberculosis (TB) incidence. We estimate here
      whether being undocumented is a determinant of TB, independently of origin. Cross
      sectional study including undocumented migrants in a TB screening program in
      2002; results were compared to 12,904 age and frequency matched participants in a
      general TB screening program conducted at various workplaces in Geneva,
      Switzerland from 1992 to 2002. A total of 206 undocumented migrants (36% male,
      64% female, mean age 37.8 years (SD 11.8), 82.5% from Latin America) participated
      in the TB screening program. Compared to legal residents, undocumented migrants
      had an adjusted OR for TB-related fibrotic signs of 1.7 (95% CI 0.8;3.7). The OR
      of TB-related fibrotic signs for Latin American (vs. other) origin was 2.7 (95%
      CI 1.6;4.7) among legal residents and 5.5 (95% CI 2.8;10.8) among undocumented
      migrants. Chest X-ray screening identified a higher proportion of TB-related
      fibrotic signs among Latin Americans, independently of their residency status.

PMID- 19582583
TI  - Ambiguity advantage revisited: two meanings are better than one when accessing
      Chinese nouns.
AB  - This paper revisits the effect of lexical ambiguity in word recognition, which
      has been controversial as previous research reported advantage, disadvantage, and
      null effects. We discuss factors that were not consistently treated in previous
      research (e.g., the level of lexical ambiguity investigated, parts of speech of
      the experimental stimuli, and the choice of non-words) and report on a lexical
      decision experiment with Chinese nouns in which ambiguous nouns with homonymic
      and/or metaphorical meanings were contrasted with unambiguous nouns. An ambiguity
      advantage effect was obtained-Chinese nouns with multiple meanings were
      recognized faster than those with only one meaning. The results suggested that
      both homonymic and metaphorical meanings are psychologically salient semantic
      levels actively represented in the mental lexicon. The results supported a
      probability-based model of random lexical access with multiple meanings
      represented by separate semantic nodes. We further discuss these results in terms
      of lexical semantic representation and how different experimental paradigms
      result in different ambiguity effects in lexical access.

PMID- 19582584
TI  - Morpho-histochemical characterization of salivary gland cells of males of the
      tick Rhipicephalus sanguineus (Acari: Ixodidae) at different feeding stages:
      description of new cell types.
AB  - This study describes the changes undergone by cells of the salivary glands of
      unfed and feeding (at day two and four post-attachment) Rhipicephalus sanguineus
      males, as well as new cell types. In unfed males, types I and II acini are
      observed with cells "undifferentiated", undefined 1 and 2 (the latter, with
      atypical granules), a, c1 and c3; type III is composed of cells d and e; and type
      IV present cells g. In males at day two post-attachment, type I acini exhibit the
      same morphology of unfed individuals. An increase in size is observed in types
      II, III, and IV, as cells are filled with secretion granules. Some granules are
      still undergoing maturation. In type II acinus, cells a, b and c1-c8 are
      observed. Cells c7 and c8 are described for the first time. Cells c7 are termed
      as such due to the addition of polysaccharides in the composition of the
      secretion granules (in unfed individuals, they are termed undefined 1). Type III
      acini exhibit cells d and e completely filled with granules, and in type IV,
      cells g contain granules in several stages of maturation. In males at day four
      post-attachment, type I acini do not exhibit changes. Granular acini exhibit
      cells with fewer secretion granules, which are already mature. In type II acini,
      cells a, b, c1-c5 are present, type III exhibit cells d and e, and type IV
      contain cells g with little or no secretion. This study shows that in the
      salivary glands of R. sanguineus males, cells a, c1, and c3 of type II acinus,
      and cells d and e of type III do not exhibit changes in granular content,
      remaining continuously active during the entire feeding period. This indicates
      that during the intervals among feeding stages, gland cells reacquire the same
      characteristics found in unfed individuals, suggesting that they undergo
      reprogramming to be active in the next cycle.

PMID- 19582585
TI  - Screening pharmaceuticals for possible carcinogenic effects: initial positive
      results for drugs not previously screened.
AB  - OBJECTIVE: To screen commonly used prescription drugs for possible carcinogenic
      effects. METHODS: In a large health care program we identified 105 commonly used
      drugs, not previously screened. Recipients were followed for up to 121/2 years
      for incident cancer. Nested case-control analyses of 55 cancer sites and all
      combined included up to ten matched controls per case, with lag of at least 2
      years between drug dispensing and cancer. Positive associations entailed a
      relative risk of 1.50, with p <= 0.01 and higher risk for three or more, than for
      one prescription. Evaluation included further analyses, searches of the
      literature, and clinical judgment. RESULTS: There were 101 associations of
      interest for 61 drugs. Sixty-six associations were judged to have involved
      substantial confounding. We found evidence that of the remaining 35, the
      following associations may not be due to chance: sulindac with gallbladder cancer
      and leukemia, hyoscyamine with nonHodgkin lymphoma, nortriptyline with esophageal
      and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine
      with testicular cancer, hydrochlorothiazide with renal and lip cancer, and
      nifedipine with lip cancer. CONCLUSIONS: These preliminary findings suggest that
      further studies are indicated regarding sulindac, hyoscyamine, nortriptyline,
      oxazepam, fluoxetine, paroxetine, hydrochlorothiazide, and nifedipine.

PMID- 19582586
TI  - Ugi-Smiles couplings: new entries to N-aryl carboxamide derivatives.
AB  - The scope of the Ugi reaction has been extended by the use of phenols as
      carboxylic acid surrogates to afford N-aryl carboxamides. A Smiles rearrangement
      occurs as the last step of the mechanism instead of the classical final Mumm
      process. Various parameters concerning the nature of these inputs have been
      studied: the use of heteroaromatic derivatives, the substitution of the hydroxyl
      moiety by a thio entity (to afford functionalized thioamides), as well as the
      influence of the nature and position of substituents on the phenol. A three
      component version (Passerini-Smiles) of this coupling has been developed as well.
      Following these couplings, various post-condensation transformations have been
      performed to reach more complex heteroaromatic fused systems. The easy
      functionalizations of phenols offer many opportunities for cyclization
      strategies: the reduction of the nitro group allows the formation of o
      phenylenediamine derivatives, which, in turn, can be transformed into
      quinoxalines, benzotriazoles, and benzimidazoles. Various organometallic
      reactions of the Ugi-Smiles adducts have been successfully carried out, either
      from iodophenols (Heck couplings to give indoles, Ullmann reaction to form
      quinoxalines), or from allyl pyrimidines (azepine formation by RCM strategy) as
      starting phenol inputs. Finally, a new palladium-mediated oxidative cyclization
      led to the formation of tricyclic systems.

PMID- 19582587
TI  - Towards the production of high levels of eicosapentaenoic acid in transgenic
      plants: the effects of different host species, genes and promoters.
AB  - Eicosapentaenoic acid (EPA, 20:5n-3) plays an important role in many aspects of
      human health. In our efforts towards producing high levels of EPA in plants, we
      investigated the effects of different host species, genes and promoters on EPA
      biosynthesis. Zero-erucic acid Brassica carinata appeared to be an outstanding
      host species for EPA production, with EPA levels in transgenic seed of this line
      reaching up to 25%. Two novel genes, an 18-carbon omega3 desaturase (CpDesX) from
      Claviceps purpurea and a 20-carbon omega3 desaturase (Pir-omega3) from Pythium
      irregulare, proved to be very effective in increasing EPA levels in high-erucic
      acid B. carinata. The conlinin1 promoter from flax functioned reasonably well in
      B. carinata, and can serve as an alternative to the napin promoter from B. napus.
      In summary, the judicious selection of host species and promoters, together with
      the inclusion of genes that enhance the basic very long chain polyunsaturated
      fatty acid biosynthetic pathway, can greatly influence the production of EPA in
      plants.

PMID- 19582589
TI  - Dietary phytochemicals as rumen modifiers: a review of the effects on microbial
      populations.
AB  - In the recent years, the exploration of bioactive phytochemicals as natural feed
      additives has been of great interest among nutritionists and rumen
      microbiologists to modify the rumen fermentation favorably such as defaunation,
      inhibition of methanogenesis, improvement in protein metabolism, and increasing
      conjugated linoleic acid content in ruminant derived foods. Many phytochemicals
      such as saponins, essential oils, tannins and flavonoids from a wide range of
      plants have been identified, which have potential values for rumen manipulation
      and enhancing animal productivity as alternatives to chemical feed additives.
      However, their effectiveness in ruminant production has not been proved to be
      consistent and conclusive. This review discusses the effects of phytochemicals
      such as saponins, tannins and essential oils on the rumen microbial populations,
      i.e., bacteria, protozoa, fungi and archaea with highlighting molecular diversity
      of microbial community in the rumen. There are contrasting reports of the effects
      of these phytoadditives on the rumen fermentation and rumen microbes probably
      depending upon the interactions among the chemical structures and levels of
      phytochemicals used, nutrient composition of diets and microbial components in
      the rumen. The study of chemical structure-activity relationships is required to
      exploit the phytochemicals for obtaining target responses without adversely
      affecting beneficial microbial populations. A greater understanding of the
      modulatory effects of phytochemicals on the rumen microbial populations together
      with fermentation will allow a better management of the rumen ecosystem and a
      practical application of this feed additive technology in livestock production.

PMID- 19582590
TI  - From industrial sites to environmental applications with Cupriavidus
      metallidurans.
AB  - Cupriavidus metallidurans CH34 and related strains are adapted to metal
      contaminated environments. A strong resistance to environmental stressors and
      adaptation make it ideal strains for survival in decreasing biodiversity
      conditions and for bioaugmentation purposes in environmental applications. The
      soil bacterium C. metallidurans is able to grow chemolithoautotrophically on
      hydrogen and carbon dioxide allowing a strong resilience under conditions lacking
      organic matter. The biofilm growth on soil particles allows coping with
      starvation or bad conditions of pH, temperature and pollutants. Its genomic
      capacity of two megaplasmids encoding several heavy metal resistance operons
      allowed growth in heavy metal contaminated habitats. In addition its specific
      siderophores seem to play a role in heavy metal sequestration besides their role
      in the management of bioavailable iron. Efflux ATPases and RND systems pump the
      metal cations to the membrane surface where polysaccharides serve as heavy metal
      binding and nucleation sites for crystallisation of metal carbonates. These
      polysaccharides contribute also to flotation under specific conditions in a soil
      heavy metals-bacteria suspension mixture. An inoculated moving bed sand filter
      was constructed to treat heavy metal contaminated water and to remove the metals
      in the form of biomass mixed with metal carbonates. A membrane based contactor
      allowed to use the bacteria as well in a versatile wastewater treatment system
      and to grow homogeneously formed heavy metal carbonates. Its behaviour toward
      heavy metal binding and flotation was combined in a biometal sludge reactor to
      extract and separate heavy metals from metal contaminated soils. Finally its
      metal-induced heavy metal resistance allowed constructing whole cell heavy metal
      biosensors which, after contact with contaminated soil, waste, solids, minerals
      and ashes, were induced in function of the bioavailable concentration (Cd, Zn,
      Cu, Cr, Co, Ni, Tl, Pb and Hg) in the solids and allowed to investigate the
      speciation of immobilization of those metals.

PMID- 19582588
TI  - NGAL: a biomarker of acute kidney injury and other systemic conditions.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein belonging
      to the lipocalin superfamily. It was initially found in activated neutrophils,
      however, many other cells, like kidney tubular cells, may produce NGAL in
      response to various insults. Recently, it has been found to have a role in iron
      metabolism by virtue of its binding with siderophores. It has also been found to
      have a role in kidney development and tubular regeneration after injury. In
      experimental studies, it was found to be highly expressed in response to tubular
      injury. In subsequent clinical studies, urine NGAL has been found to be an early
      predictor for acute kidney injury (AKI). Newer devices for early bedside
      detection of NGAL are now available. Since serum creatinine is known to be an
      inadequate and late marker of AKI, NGAL might soon emerge as a troponin-like
      early marker for AKI. Recent evidence also suggests its role as a biomarker in a
      variety of other renal and non-renal conditions.

PMID- 19582591
TI  - Chromatic photoacclimation extends utilisable photosynthetically active radiation
      in the chlorophyll d-containing cyanobacterium, Acaryochloris marina.
AB  - Chromatic photoacclimation and photosynthesis were examined in two strains of
      Acaryochloris marina (MBIC11017 and CCMEE5410) and in Synechococcus PCC7942.
      Acaryochloris contains Chl d, which has an absorption peak at ca 710 nm in vivo.
      Cultures were grown in one of the three wavelengths (525 nm, 625 nm and 720 nm)
      of light from narrow-band photodiodes to determine the effects on pigment
      composition, growth rate and photosynthesis: no growth occurred in 525 nm light.
      Synechococcus did not grow in 720 nm light because Chl a does not absorb
      effectively at this long wavelength. Acaryochloris did grow in 720 nm light,
      although strain MBIC11017 showed a decrease in phycobilins over time. Both
      Synechococcus and Acaryochloris MBIC11017 showed a dramatic increase in
      phycobilin content when grown in 625 nm light. Acaryochloris CCMEE5410, which
      lacks phycobilins, would not grow satisfactorily under 625 nm light. The cells
      adjusted their pigment composition in response to the light spectral conditions
      under which they were grown. Photoacclimation and the Q (y) peak of Chl d could
      be understood in terms of the ecological niche of Acaryochloris, i.e. habitats
      enriched in near infrared radiation.

PMID- 19582592
TI  - Measuring pain in the context of homelessness.
AB  - PURPOSE: The primary objective of this study was to inform the development of
      measures of pain impact appropriate for all respondents, including homeless
      individuals, so that they can be used in clinical research and practice. The
      secondary objective was to increase understanding about the unique experience of
      homeless people with pain. METHODS: Seventeen homeless individuals with chronic
      health conditions (often associated with pain) participated in cognitive
      interviews to test the functioning of 56 pain measurement items and provided
      information about their experience living with and accessing treatment for pain.
      RESULTS: The most common problems identified with items were that they lacked
      clarity or were irrelevant in the context of homelessness. Items that were
      unclear, irrelevant and/or had other identified problems made it difficult for
      participants to respond. Participants also described multiple ways in which their
      pain was exacerbated by conditions of homelessness and identified barriers to
      accessing appropriate treatment. CONCLUSIONS: Results suggested that the majority
      of items were problematic for the homeless and require substantial modifications
      to make the pain impact bank relevant to this population. Additional
      recommendations include involving homeless in future item bank development,
      conducting research on the topic of pain and homelessness, and using cognitive
      interviewing in other types of health disparities research.

PMID- 19582593
TI  - Positive allosteric interaction of structurally diverse T-type calcium channel
      antagonists.
AB  - Low-voltage-activated (T-type) calcium channels play a role in diverse
      physiological responses including neuronal burst firing, hormone secretion, and
      cell growth. To better understand the biological role and therapeutic potential
      of the target, a number of structurally diverse antagonists have been identified.
      Multiple drug interaction sites have been identified for L-type calcium channels,
      suggesting a similar possibility exists for the structurally related T-type
      channels. Here, we radiolabel a novel amide T-type calcium channel antagonist
      (TTA-A1) and show that several known antagonists, including mibefradil,
      flunarizine, and pimozide, displace binding in a concentration-dependent manner.
      Further, we identify a novel quinazolinone T-type antagonist (TTA-Q4) that
      enhanced amide radioligand binding, increased affinity in a saturable manner and
      slowed dissociation. Functional evaluation showed these compounds to be state
      dependent antagonists which show a positive allosteric interaction. Consistent
      with slowing dissociation, the duration of efficacy was prolonged when compounds
      were co-administered to WAG/Rij rats, a genetic model of absence epilepsy. The
      development of a T-type calcium channel radioligand has been used to demonstrate
      structurally distinct TTAs interact at allosteric sites and to confirm the
      potential for synergistic inhibition of T-type calcium channels with structurally
      diverse antagonists.

PMID- 19582594
TI  - Hepatocellular carcinoma cells deteriorate the biophysical properties of
      dendritic cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells and induce antigen
      specific immune responses in the organism. The dysfunction of DCs has been
      implicated in tumor-bearing host. In order to elucidate the effects of tumor
      microenvironment on the functions of DCs from interdisciplinary aspects, we
      characterized the biophysical properties of DCs co-cultured with hepatocellular
      carcinoma cells (HCC). The results showed that the biophysical characteristics of
      immature and mature DCs were severely impaired by HCC compared with those under
      normal conditions, including the increased osmotic fragilities, decreased cell
      membrane fluidities, increased membrane viscoelastic properties, dysfunction and
      increased expression of cytoskeleton protein F-actin, as well as the deteriorated
      transendothelium migration. The impaired biophysical properties of DCs may be one
      of many aspects of the immune escape mechanisms of tumors. These results are
      clinically and instructionally significant with regard to how to enhance
      efficiency of the anti-tumor therapy based on DCs.

PMID- 19582595
TI  - Role of human liver microsomes in in vitro metabolism of drugs-a review.
AB  - Drug metabolism studies are essential and necessary during the evaluation of
      drugs. This review discusses the in vitro human liver models to estimate the drug
      metabolic fates in vivo. Different approaches are provided and emphasis is placed
      on the potential of human liver microsomes for drug metabolism and inhibition
      studies. The methodology for these studies using human liver microsomes,
      applications of human liver microsomes, and the drugs studied by human liver
      microsomes are listed. Human liver microsomes represent a critical experimental
      model for the evaluation of drug metabolites with a high probability of clinical
      success.

PMID- 19582596
TI  - Postpericardial injury syndrome: an autoimmune phenomenon.
AB  - Postpericardial injury syndrome (PPIS) is defined as pericarditis or pericardial
      effusion that results from recent or earlier injury of the pericardium. The
      clinical features of this syndrome include fever, leukocytosis, and elevated
      erythrocyte sedimentation rate. Recent studies have established a connection
      between this clinical presentation and an underlying autoimmune process. The role
      of the humoral immune response is well established regarding the pathogenesis of
      PPIS with elevated titers of different antibodies and immune complexes in the
      circulation correlating with disease activity. Nevertheless, cell-mediated
      response by different subgroups of T lymphocyte has a significant importance with
      direct infiltration of pericardial tissue and fluids. The diagnosis of PPIS is
      still challenging. A strong connection between specific serological immunological
      markers and the disease would be of great value in diagnosis and treatment.

PMID- 19582625
TI  - Advanced access scheduling.

PMID- 19582597
TI  - Multiple myeloma: management of adverse events.
AB  - The combination of conventional chemotherapy or dexamethasone with new drugs,
      such as immunomodulatory agents and proteasome inhibitors, has substantially
      changed the treatment paradigm of myeloma patients. New drugs have been
      incorporated in pre-transplant induction regimens and post-transplant
      consolidation and maintenance strategies for young patients; in elderly patients,
      standard melphalan and prednisone (MP) plus thalidomide or plus bortezomib are
      now considered standards of care, and ongoing trials are assessing if
      lenalidomide plus standard MP or plus low-dose dexamethasone may be other
      options. The efficacy of these drugs needs to be balanced against their toxicity.
      Different drugs have a different toxicity profile. The choice for the best
      treatment strategy for every single patient should be based on results of
      scientific randomized studies but tailored to account for patient's biological
      age, comorbidities, and the expected toxicity profile of different regimens.
      Prompt dose reduction and accurate management of treatment-related toxicity can
      greatly reduce early discontinuation rate and significantly improve treatment
      efficacy. This chapter will focus on frequency and management of main adverse
      events in newly diagnosed and relapsed myeloma patients and will provide
      guidelines for dose reductions and supportive therapy.

PMID- 19582627
TI  - A point system for resident scholarly activity.
AB  - Encouraging resident scholarly activity is challenging. One Army family medicine
      program was struggling to get residents to fulfill their requirements. Projects
      were not being completed, and publication or presentation of results was rare. A
      novel "scholarly activity point" system was introduced that expanded the types of
      scholarly activity residents could participate in while still encouraging
      clinical research. Since implementation, the number of residents successfully
      publishing and presenting scholarly projects has risen sharply. The point system
      has resulted in an increase in resident enthusiasm for scholarship, a change in
      the academic culture, and a dramatic rise in scholarly output.

PMID- 19582628
TI  - Reflections on a rotation in appalachia.

PMID- 19582629
TI  - Noises from below.

PMID- 19582630
TI  - Demystifying the discipline of medical humanities at the resident level.

PMID- 19582631
TI  - The University of Missouri integrated residency: evaluating a 4-year curriculum.
AB  - BACKGROUND AND OBJECTIVES: Several approaches to merging residency training and
      medical school education have been attempted over the past 20 years. This study
      describes and evaluates an integrated family medicine residency programa 4-year
      program that overlaps with the final year of medical school. METHODS: We
      retrospectively analyzed multiple data sources, including In-Training Examination
      scores, patient visit profiles, resident demographics, and graduate surveys.
      RESULTS: Integrated residents (IRs) perform significantly better than traditional
      residents on In-Training Examinations at each year of residency training, with
      the difference in mean scores decreasing over time (67.8, 39.6, and 33.0 points
      better in the first, second, and third residency years). No evidence of increased
      patient continuity or panel size was noted. A higher proportion of IRs serve as
      chief residents, rate their residency experience as "excellent," and remain with
      the program through graduation. Practice characteristics immediately after
      residency do not significantly differ. Financial benefits are evident for the IRs
      as well as the hosting department. CONCLUSIONS: This integrated program offers
      several benefits for both the medical student and the residency program, and it
      is a potential model for academic residencies aiming to recruit and retain a
      higher percentage of their own schools' students.

PMID- 19582632
TI  - Elder abuse education in primary care residency programs: a cluster group
      analysis.
AB  - BACKGROUND AND OBJECTIVES: Elder abuse is a serious issue, affecting up to 10% of
      community-dwelling older adults. This project sought to understand if elder abuse
      under-reporting was related to physician specialty and residency training.
      METHODS: A 17-item survey focusing on program demographics, current curriculum,
      priority of elder abuse education, clinical and didactic experiences, and triage
      resources was mailed to directors of all Michigan primary care residencies
      approved by the Accreditation Council for Graduate Medical Education. RESULTS:
      Clustering by program type, family medicine programs were primarily represented
      in the high-intensity group (standard residual -1.6), while internal medicine
      programs were primarily represented in the low-intensity group (standard residual
      2.5, X2=14.80, df=6). Emergency medicine comprised the mid-intensity groups. The
      high- intensity group scored very high or high on areas including knowledge of
      elder abuse facts, elder abuse curriculum and training, and awareness of
      community resources related to elder abuse. CONCLUSIONS: Family medicine
      residency programs appear to address elder abuse more comprehensively than do
      emergency medicine and internal medicine programs. These programs may need to
      consider additional curriculum and clinical experience in elder abuse.

PMID- 19582633
TI  - Implementation of STFM's "Smiles for Life" oral health curriculum in a medical
      school interclerkship.
AB  - BACKGROUND AND OBJECTIVES: While oral health is an important topic for medical
      education, it is often not covered in medical school. The Association of American
      Medical Colleges (AAMC) has recently set guidelines for oral health training in
      medical education. Our objective was to demonstrate how a mandatory
      interclerkship (half-day workshops taught between third-year clerkships) that
      covers pediatric, urgent care, examination skills, and prevention topics in oral
      health can lead to an increase in knowledge for medical students. METHODS:
      Teaching methods included the use of interactive lectures, an audience response
      system, and small-group workshops taught by medical and dental educators. The
      curriculum was based on the Society of Teachers of Family Medicine (STFM) Smiles
      for Life National Oral Health Curriculum. Students were given pretests and
      posttests, including a 6-month follow-up test. RESULTS: Students showed a
      significant improvement in knowledge between pretesting and immediate posttesting
      across a range of topics. Long-term knowledge retention was more limited. The
      majority of students reported enthusiasm for this topic and found the materials
      essential for their training. CONCLUSIONS: A brief interclerkship can improve
      medical students' oral health knowledge and be engaging. More research is needed
      to evaluate means to sustaining the knowledge.

PMID- 19582634
TI  - The joy of reviewing: a short guide to writing book and media reviews.

PMID- 19582636
TI  - Effect of a computerized body mass index prompt on diagnosis and treatment of
      adult obesity.
AB  - BACKGROUND: In obese adults, physicians often fail to identify obesity and
      recommend treatments for it. We sought to determine whether a computerized body
      mass index (BMI) chart prompt would increase the likelihood that patients of
      family physicians would be diagnosed with obesity and referred for obesity
      treatment. METHODS: A total of 846 obese patients of 37 family physicians were
      randomly assigned to either have a patient's BMI chart prompt placed in their
      electronic medical record (intervention group) or not have a BMI prompt
      (comparison group) placed in the record. We then examined patient medical records
      for evidence of an obesity diagnosis and referral for specific obesity
      treatments. We also measured whether the presence of comorbidities in obese
      patients influenced the likelihood of diagnoses and treatments by the physicians.
      RESULTS: Obese patients of physicians who had a BMI chart prompt in their medical
      records were significantly more likely than obese patients of physicians who did
      not receive a BMI chart prompt to receive a diagnosis of obesity (16.6% versus
      10.7%; P=.016). Patients of physicians who were provided with a BMI chart prompt
      were also more likely than patients of physicians who did not get a chart prompt
      to receive a referral for diet treatment (14.0% versus 7.3%, P=.002) and exercise
      (12.1% versus 7.1%, P=.016). Of the obesity comorbidities, only obstructive sleep
      apnea (OSA) was a predictor of a patient being diagnosed with obesity (OR=.49,
      95% CI=0.281, 0.869, P=.014). CONCLUSIONS: Inclusion of a computerized BMI chart
      prompt increased the likelihood that physicians would diagnose obesity in obese
      patients and refer them for treatment.

PMID- 19582635
TI  - Practitioner empathy and the duration of the common cold.
AB  - OBJECTIVE: This study's objective was to assess the relationship of empathy in
      medical office visits to subsequent outcomes of the common cold. METHODS: A total
      of 350 subjects ? 12 years of age received either a standard or enhanced
      physician visit as part of a randomized controlled trial. Enhanced visits
      emphasized empathy on the part of the physician. The patient-scored Consultation
      and Relational Empathy (CARE) questionnaire assessed practitioner-patient
      interaction, especially empathy. Cold severity and duration were assessed from
      twice-daily symptom reports. Nasal wash was performed to measure the immune
      cytokine interleukin-8 (IL-8). RESULTS: Eighty-four individuals reported perfect
      (score of 50) CARE scores. They tended to be older with less education but
      reported similar health status, quality of life, and levels of optimism. In those
      with perfect CARE scores, cold duration was shorter (mean 7.10 days versus 8.01
      days), and there was a trend toward reduced severity (mean area under receiver
      operator characteristics curve 240.40 versus 284.49). After accounting for
      possible confounding variables, cold severity and duration were significantly
      lower in those reporting perfect CARE scores. In these models, a perfect score
      also correlated with a larger increase in IL-8 levels. CONCLUSIONS: Clinician
      empathy, as perceived by patients with the common cold, significantly predicts
      subsequent duration and severity of illness and is associated with immune system
      changes.

PMID- 19582637
TI  - Adoption of electronic medical records in family practice: the providers'
      perspective.
AB  - BACKGROUND AND OBJECTIVES: The study's objectives were to explore Deliver Primary
      Healthcare Information (DELPHI) project participants' experiences, ideas, and
      perspectives regarding the adoption of electronic medical records (EMRs) into
      their primary health care practices and to examine perceived barriers and
      facilitators to EMR adoption. METHODS: This study explored the experiences of the
      30 participants in the project. Semi-structured interviews were conducted. The
      analysis was both iterative and interpretive. RESULTS: Two key themes emerged:
      (1) barriers (ie, level of computer literacy, training required, and time) and
      facilitators (ie, having an in-house problem solver and the EMR's integrated
      messaging system), and (2) a continuum of EMR adoption (ie, levels of knowledge
      ranging from novice to advanced and responses to the EMR that included
      participants' reflections on their personal journey across the adoption continuum
      and that of their practice sites). CONCLUSIONS: It is important to be aware of
      and responsive to factors that can influence EMR implementation and adoption.
      They include paying attention to computer literacy; setting aside dedicated time
      for EMR implementation and adoption, as well as engaging in training activities;
      and supporting problem-solvers in the practice. Mechanisms should be put into
      place to promote the movement of practices across the continuum of EMR adoption.

PMID- 19582638
TI  - EMRs for improving quality of care: promise and pitfalls.

PMID- 19582639
TI  - The birth of a house call practice.
AB  - Increasingly, physicians of all specialties are frustrated with the complex,
      unrewarding system of third-party billing in the United States. It has led many
      physicians to wonder how best to change their practice to ameliorate these
      challenges or leave their practice altogether. It is possible that family
      physicians suffer most because they are trained to provide comprehensive care to
      all comers, regardless of reimbursement status. What they may not know is that
      leaving the practice might be the best thing for everyone, and it doesn't
      necessarily mean leaving medicine! As I realized during my experiences working in
      South Florida, transitioning to a house call practice can be emotionally and
      financially rewarding.

PMID- 19582640
TI  - A short form of the Posttraumatic Growth Inventory.
AB  - A short form of the Posttraumatic Growth Inventory (PTGI-SF) is described. A
      sample of 1351 adults who had completed the Posttraumatic Growth Inventory (PTGI)
      in previous studies provided the basis for item selection. The resulting 10-item
      form includes two items from each of the five subscales of the original PTGI,
      selected on the basis of loadings on the original factors and breadth of item
      content. A separate sample of 186 completed the short form of the scale (PTGI
      SF). Confirmatory factor analyses on both data sets demonstrated a five-factor
      structure for the PTGI-short form (PTGI-SF) equivalent to that of the PTGI. Three
      studies of homogenous clinical samples (bereaved parents, intimate partner
      violence victims, and acute leukemia patients) demonstrated that the PTGI-SF
      yields relationships with other variables of interest that are equivalent to
      those found using the original form of the PTGI. A final study demonstrated that
      administering the 10 short-form items in a random order, rather than in the fixed
      context of the original scale, did not impact the performance of the PTGI-SF.
      Overall, these results indicate that the PTGI-SF could be substituted for the
      PTGI with little loss of information.

PMID- 19582641
TI  - Application of Failure Mode and Effect Analysis (FMEA) and cause and effect
      analysis in conjunction with ISO 22000 to a snails (Helix aspersa) processing
      plant; A case study.
AB  - Failure Mode and Effect Analysis (FMEA) has been applied for the risk assessment
      of snails manufacturing. A tentative approach of FMEA application to the snails
      industry was attempted in conjunction with ISO 22000. Preliminary Hazard Analysis
      was used to analyze and predict the occurring failure modes in a food chain
      system (snails processing plant), based on the functions, characteristics, and/or
      interactions of the ingredients or the processes, upon which the system depends.
      Critical Control points have been identified and implemented in the cause and
      effect diagram (also known as Ishikawa, tree diagram, and fishbone diagram). In
      this work a comparison of ISO22000 analysis with HACCP is carried out over snails
      processing and packaging. However, the main emphasis was put on the
      quantification of risk assessment by determining the RPN per identified
      processing hazard. Sterilization of tins, bioaccumulation of heavy metals,
      packaging of shells and poisonous mushrooms, were the processes identified as the
      ones with the highest RPN (280, 240, 147, 144, respectively) and corrective
      actions were undertaken. Following the application of corrective actions, a
      second calculation of RPN values was carried out leading to considerably lower
      values (below the upper acceptable limit of 130). It is noteworthy that the
      application of Ishikawa (Cause and Effect or Tree diagram) led to converging
      results thus corroborating the validity of conclusions derived from risk
      assessment and FMEA. Therefore, the incorporation of FMEA analysis within the
      ISO22000 system of a snails processing industry is considered imperative.

PMID- 19582642
TI  - Comparative hazard characterization in food toxicology.
AB  - Historically, different approaches have been adopted for comparing and
      characterizing hazards that can be found in the very complex mixture of
      substances present in food. In this review a variety of prominent risk assessment
      models are evaluated in the context of food safety. In their current state of
      refinement, though, they show limited applicability for comparative hazard
      characterization and impact magnitude scoring of adverse effects of substances in
      food. Nonetheless, some existing models hold building blocks and modelling
      concepts that appear promising for further development and integration. Thus, a
      new, dedicated, and generally accepted model is needed that is capable of
      generating relevant "Impact Magnitude Score" (IMS) values for comparing
      potentially toxic substances in food. A brief outline of requirements for a model
      (Guided Toxicology-assessment of Health Impact; GTHI) is presented that considers
      "severity" (S), "duration" (D), and "proportion of population affected" (P). An
      important demand on such a model is to provide significantly improved food safety
      evaluation amenable to regulatory agencies and consumers. This review is based on
      a project entitled "Promoting food safety through a new integrated risk analysis
      approach for foods" (acronym: "SAFE FOODS") that is under the subsidy of the
      European Commission.

PMID- 19582643
TI  - Integration of risk and benefit analysis-the window of benefit as a new tool?
AB  - Foods and food components can have positive and/or negative effects on our
      health, resulting in benefits and risks. At present these are evaluated in
      largely separated trajectories. In view of assessment, management, and
      communication, we here propose and argue for an integrated evaluation of risk and
      benefit of food components and foods. The window of benefit assessment concept is
      described as a framework to combine thresholds and scores. The recommended
      dietary allowance (RDA) and the tolerable upper intake level (UL) delimit the
      range of intakes that should be considered sufficient to prevent deficiency,
      while avoiding toxicity. Within these thresholds, two additional thresholds, the
      lower and upper level of additional benefit (LLAB and ULAB), define the range of
      intakes that constitute an additional benefit. Intake within these limits should
      thus be protective against a specified health or nutritional risk of public
      health relevance. To faithfully predict outcomes and to obtain the tools that are
      necessary to support scientific valid evaluations, a mechanism based systems
      biology understanding of the effects of foods and nutrients is seen as the way
      forward. Ultimately this should lead to an integrated risk-benefit assessment,
      which will allow better management and, especially, communication, to the benefit
      of the consumer.

PMID- 19582644
TI  - Swine flu: rehearsal for disaster?

PMID- 19582645
TI  - Review of school closure as a pandemic mitigation strategy.

PMID- 19582646
TI  - Dr. Aldridge's nightmare: state OIG demands back Medicaid payments.

PMID- 19582647
TI  - SGR still standing: Congress likely to punt on long-term Medicare fee fix.

PMID- 19582648
TI  - Flagging identify theft: is the patient who he says he is?

PMID- 19582649
TI  - Blood feud: controversy arises over newborn screening program.

PMID- 19582650
TI  - Bundling payments: San Antonio project seeks lower costs, improved care.

PMID- 19582651
TI  - [Depression and dementia--a multifaceted relation].

PMID- 19582652
TI  - [Sensitivity of neurochemical dementia diagnostics in CSF compared to 99mTc-SPECT
      in Alzheimer's dementia].
AB  - The diagnosis of Alzheimer's dementia is currently changing from a late and
      exclusion diagnosis towards a pathophysiology-based early and positive diagnosis.
      Especially advances in neuro-chemical dementia diagnostics in the cerebrospinal
      fluid (NDD-CSF) and imaging techniques like PET, SPECT or MRI are of particular
      interest. Unfortunately, many studies investigated only either one or other
      technique. In the present study 56 patients (average 67.1 years; average mini
      mental status test (MMST) 22.2) were examined with the clinical diagnosis of
      Alzheimer's dementia. All patients both underwent NDD-CSF as well as 99mTc-SPECT.
      Only the SPECT, but not the NDD-CSF correlated with disease severity. Sensitivity
      of NDD-CSF was 89 % and SPECT 48 % for all patients and 93 % resp. 61 % for
      patients with MMST < 24. Below MMST 20 both methods had equal sensitivity. Both
      diagnostic techniques showed no statistic coherence (p = 0.27), neither after
      correction for subgroups like disease severity or the APOE genotype. Our results
      are compatible with the hypothesis that the NDD-CSF reflects beta-amyloid
      aggregation and Tau-Protein pathology as a pathophysiologic biomarker. Our
      results suggest that SPECT is rather a state parameter for the rCBF changes
      following cortical neurodegeneration.

PMID- 19582653
TI  - [Functional MRI of transplanted kidneys using diffusion-weighted imaging].
AB  - PURPOSE: Contrast-enhanced MRI is considered problematic in renal allograft
      recipients due to the association of gadolinium administration and the
      development of NSF. Therefore, we assessed the clinical value of mono- and
      biexponential analysis of diffusion-weighted imaging (DWI). MATERIALS AND
      METHODS: A total of 32 patients were divided into four groups: (a) patients with
      stable function of renal allograft for at least 6 months, (b) patients with acute
      deterioration of allograft function, patients who recently underwent
      transplantation (< 14 days) with good (c) or decreased (d) renal function. T 2w
      ax. and T 1w cor. and a diffusion-weighted sequence with 16 b-values (b = 0 - 750
      s/mm (2)) were performed on a 1.5 T scanner (Magnetom Avanto, Siemens Medical
      Solutions). ROI-based analysis of the renal cortex was analyzed using the
      software "Table Curve 2D". RESULTS: Monoexponential analysis showed an ADC (mono)
      of 1961 +/- 104 1801 +/- 150, 2053 +/- 169 and 1720 +/- 191 10 (-6)mm (2) /sec
      for patient group a, b, c and d respectively. The difference in ADC (mono)
      between group (a) and (b) (p < 0.006) and between group (c) and (d) (p < 0.04)
      was statistically significant. Biexponential analysis revealed a mean perfusion
      fraction of 0.21, 0.23, 0.32 and 0.24 for group (a), (b), (c) and (d),
      respectively. Biexponential ADC showed a higher numerical accuracy. There were no
      statistically significant inter-group differences in diffusion (ADC (D)) and
      perfusion (ADC (P)). CONCLUSION: Unenhanced evaluation of renal allografts with
      DWI is feasible. ADC (mono) of renal cortex correlates with renal function. The
      significance of the higher numerical accuracy of biexponential analysis in
      clinical settings requires further evaluation in larger-scale studies.

PMID- 19582654
TI  - RECIST and WHO criteria evaluation of cervical, thoracic and abdominal lymph
      nodes in patients with malignant lymphoma: manual versus semi-automated
      measurement on standard MDCT slices.
AB  - PURPOSE: Since semi-automated lesion quantification may be more precise than
      manual uni- and bidimensional measurements, the purpose of this study was to
      compare semi-automated with manual evaluations of cervical, thoracic and
      abdominal lymph nodes in patients with malignant lymphoma. MATERIALS AND METHODS:
      62 patients with known malignant lymphoma underwent staging with contrast
      enhanced 16-MDCT (16x0.7 mm coll., 120 kV, cervical/thoracic/abdominal:
      150/120/160 mAseff., 1/1.25 /1 pitch, 4/3 - 5/4 - 5/4 slice
      thickness/reconstruction increment). On the basis of these standard reconstructed
      slices, each lesion was quantified in terms of RECIST and its longest
      orthographic diameter using a semi-automated software tool (Syngo CT Oncology,
      Siemens Medical Solutions, Forchheim, Germany) and manually by an experienced
      radiologist. The degree of agreement between manual measurements and software
      quantification was statistically assessed by computing the concordance
      correlation coefficient kappa and represented graphically in corresponding Bland
      Altman plots. RESULTS: 74/80 cervical, 51/80 thoracic and 75/80 abdominal lymph
      nodes were correctly evaluated by the software. A strong degree of agreement
      between both measurement techniques (RECIST diameter: kappa = 0.97
      (cervical)/0.98 (thoracic)/0.99 (abdominal); longest orthographic diameter: kappa
      = 0.97/0.93/0.97) was obtained. CONCLUSION: Semi-automated measurement of
      cervical, thoracic and abdominal lymph nodes showed valid results on standard
      axial reconstructions compared to manual quantification with the limitation of a
      high false segmentation rate in thoracic lymph nodes.

PMID- 19582655
TI  - [Effort, accuracy and histology of MR-guided vacuum biopsy of suspicious breast
      lesions--retrospective evaluation after 389 interventions].
AB  - The aim of this study was to evaluate the effort, accuracy, histological
      diagnoses and value of MR-guided vacuum biopsy (10-gauge, 9-gauge) as the
      diagnostic procedure for suspicious breast lesions visible on MRI alone. 389 MR
      guided vacuum biopsies of suspicious MRM findings were performed in 365 patients
      either with a Vacora system (10G, Bard Company) or an ATEC system (9G, Suros
      Company). The retrospective study included the number of specimens, the table
      time, the complication rate, and the histopathological results for open biopsy
      and the findings after follow-up. The study included 341 unilateral unilocular,
      12 unilateral bilocular and 12 bilateral unilocular MR-guided vacuum biopsies. In
      27 patients (3.9%) the planned intervention was canceled because the lesion could
      not be reproduced. The average number of specimens was 15.1 (range 4 - 75) with
      the 10G technique and 14.6 (range 4 - 38) with the 9G technique. The table time
      was 43.2 min (range 17 - 95 min). Histology revealed concordant benign lesions in
      231 cases (59.4%), borderline lesions in 50 cases (12.8%), malignant tumors in
      106 cases (DCIS 30 [7.7%], invasive carcinoma 76 [19.5%]), and discordant
      findings in 2 cases (0.5%). The complication rate was less than 1%. MR-guided
      vacuum biopsy of the breast is an effective method for the minimally invasive
      percutaneous evaluation of suspicious breast lesions seen on MRI alone. As a
      consequence, primary open biopsy can be avoided and the rate of unnecessary
      surgical interventions reduced. There were no major differences between 10G and
      9G vacuum biopsy systems.

PMID- 19582656
TI  - [Comparison of magnetic resonance imaging signs and clinical findings in follow
      up examinations in children and juveniles with temporomandibular joint
      involvement in juvenile idiopathic arthritis].
AB  - PURPOSE: The aim of this study was to analyze the extent to which pathological
      findings of temporomandibular joint (TMJ) in magnetic resonance imaging (MRI)
      follow-up examinations are correlated with clinical symptoms in patients with TMJ
      involvement in juvenile idiopathic arthritis (JIA) over time. MATERIALS AND
      METHOD: Data from 34 patients with TMJ involvement in JIA was retrospectively
      examined. Shortly after two clinical examinations, the first MRI and the follow
      up MRI were performed. The MRI examinations took place with 1.5 T MRI. RESULTS:
      In both MRI examinations alterations on the condyle (MRI1: 88 %, MRT2: 91 %) and
      contrast enhancement (MRT1: 76 %, MRT2 65 %) were found most frequently. TMJ pain
      (65 %) and lower mouth opening capacity (65 %) were the number one finding in the
      first clinical examination. A statistically significant correlation was found
      between the alterations on the condyle and TMJ pain (p = 0.025) and between the
      alterations on the condyle and lower mouth opening capacity (p = 0.019). By
      comparing the results of the first MRI with the results of the follow-up MRI, we
      identified a trend towards a progression of TMJ arthritis, while the clinical
      follow-up showed an improvement in most patients. CONCLUSION: We found a
      discrepancy between the progressive or stable trends of pathological findings in
      follow-up MRI and the decrease in clinical symptoms over time. Therefore, follow
      up examination by MRI shows important information for correct evaluation about
      the stage of TMJ arthritis and about the need for treatment. Consequently, follow
      up examination by MRI is an appropriate addition to clinical examination in the
      therapeutic concept.

PMID- 19582657
TI  - [An unusual presentation of progressive multifocal leukoencephalopathy as
      contrast enhanced lesion].

PMID- 19582658
TI  - [Acute ascending mediastinitis due to septic arthritis of the sternoclavicular
      joint].

PMID- 19582659
TI  - [Aneurysmic bone cyst of the head of the mandible: a rare site of a benign bone
      tumor].

PMID- 19582660
TI  - [Initial manifestation of SAPHO syndrome].

PMID- 19582661
TI  - Low-frequency ultrasound permeates the human thorax and lung: a novel approach to
      non-invasive monitoring.
AB  - PURPOSE: Conventional sonography at 2 - 10 MHz cannot permeate the chest because
      ultrasound at this frequency is strongly scattered and reflected by air
      inclusions in the lungs. Therefore, sonography is considered impracticable for
      thoracic imaging. However, human thoraxes and lungs in situ were never rigorously
      probed with ultrasound at frequencies below 1 MHz. In addition, ultrasound is
      commonly applied as echo imaging rather than sound transmission. MATERIALS AND
      METHODS: Human subjects were studied with a transducer detector pair or an
      elastic thorax belt equipped with 12 sensors 5 cm apart that was wrapped around
      the thorax and a single pulse transmitter attached to the sternum. We focused on
      fast ultrasound transmission from 1 kHz to 1 MHz, coupled over thoracic
      sonotrodes. RESULTS: Between 1 Hz to 1 MHz, sound transmission through thorax and
      lungs shows three distinct bands: < 1 kHz sound is transmitted at 30 - 50 m/sec,
      between 1 - 10 kHz sound transmission is absent and > 10 kHz sound is transmitted
      with a speed of 1500 m/sec. We demonstrate that low-frequency ultrasound (10 -
      750 kHz) can permeate the thorax and permits monitoring of the air and water
      content of human lungs. In healthy subjects at 15 kHz, the difference in sound
      transmission through thorax and lungs between inspiration and expiration was
      dynamic and spanned several decades. Sound transmission during expiration was
      strongly decreased in patients suffering from pulmonary emphysema or
      pneumothorax, but increased in patients with pleural effusions. CONCLUSION: Sound
      transmission in the lungs is characterized by three distinct frequency bands. Low
      frequency ultrasound is transmitted through the lungs and may offer a novel non
      invasive approach to real time diagnostics.

PMID- 19582664
TI  - [Abbreviations: a semi-malignant neoplasia of the language culture].

PMID- 19582663
TI  - [Psychiatric psychotherapeutic psychosomatic treatment by the hospital: framework
      for the development of a multi-sector budget for regional mandatory care].

PMID- 19582667
TI  - [Quality management in psychiatric specialty clinics].

PMID- 19582695
TI  - The impact of health on individual retirement plans: self-reported versus
      diagnostic measures.
AB  - We reassess the impact of health on retirement plans of older workers using a
      unique survey-register match-up which allows comparing the retirement effects of
      potentially biased survey self-reports of health to those of unbiased register
      based diagnostic measures. The aim is to investigate whether even for narrowly
      defined health measures a divergence exists in the impacts of health on
      retirement between self-reported health and objective physician-reported health.
      Our sample consists of older workers and retirees drawn from a Danish panel
      survey from 1997 and 2002, merged to longitudinal register data. Estimation of
      measurement error-reduced and selection-corrected pooled OLS and fixed effects
      models of retirement show that receiving a medical diagnosis is an important
      determinant of retirement planning for both men and women, in fact more important
      than economic factors. The type of diagnosis matters, however. For men, the
      largest reduction in planned retirement age occurs for a diagnosis of lung
      disease while for women it occurs for musculo-skeletal disease. Except for
      cardiovascular disease, diagnosed disease is more influential in men's retirement
      planning than in women's. Our study provides evidence that men's self-report of
      myalgia and back problems and women's self-report of osteoarthritis possibly
      yield biased estimates of the impact on planned retirement age, and that this
      bias ranges between 1.5 and 2 years, suggesting that users of survey data should
      be wary of applying self-reports of health conditions with diffuse symptoms to
      the study of labor market outcomes. On the other hand, self-reported
      cardiovascular disease such as high blood pressure does not appear to bias the
      estimated impact on planned retirement.

PMID- 19582696
TI  - Modelling health and output at business cycle horizons for the USA.
AB  - In this paper we employ a theoretical framework - a simple macro model augmented
      with health - that draws guidance from the Keynesian view of business cycles to
      examine the relative importance of permanent and transitory shocks in explaining
      variations in health expenditure and output at business cycle horizons for the
      USA. The variance decomposition analysis of shocks reveals that at business cycle
      horizons permanent shocks explain the bulk of the variations in output, while
      transitory shocks explain the bulk of the variations in health expenditures. We
      undertake a shock decomposition analysis for private health expenditures versus
      public health expenditures and interestingly find that while transitory shocks
      are more important for private sector expenditures, permanent shocks dominate
      public health expenditures.

PMID- 19582697
TI  - On the consequences of placing amino groups at the TBP-DNA interface. Does TATA
      really matter?
AB  - The TATA-box binding protein (TBP) belongs to a family of structural proteins
      involved in transcription in eukaryotic cells. TBP binds in the minor groove of
      DNA and recognizes specifically the consensus sequence: 5' TATAWAWR 3' (W = A or
      T). Recent reports show that the TATA-box is only present in 10% of all human
      polymerase II promoters. Therefore, TBP must bind frequently to low affinity DNA
      sequences, possibly with help of other transcription factors. In order to
      understand the intramolecular and intermolecular interactions that lead to the
      consensus sequence preferred by TBP, we use high resolution crystallographic
      structures of cognate TBP-DNA complexes as templates onto which 16 dinucleotide
      repeating sequence DNA oligomers were built. The binding free energy of each
      complex was calculated using the Molecular Mechanics/Poisson-Boltzmann Solvent
      Accessible (MM-PBSA) approximation. Parsing of the free energy components allowed
      us to identify the most important contributions to sequence selectivity: DNA
      deformation and the interaction energy between TBP residues and DNA bases, as
      expected. Surprisingly, poor interaction energies lead to larger deformation
      costs, suggesting strategies to improve affinity and selectivity. Local analysis
      of the TBP-DNA interface allowed us to build interaction and deformation energy
      tables that were used, without the need to fit their relative weights, to predict
      successfully both the consensus sequence for TBP, and relative binding affinities
      for a collection of TATA box variants.

PMID- 19582698
TI  - SCHIP premiums, enrollment, and expenditures: a two state, competing risk
      analysis.
AB  - Faced with state budget troubles, policymakers may introduce or increase State
      Children's Health Insurance Program (SCHIP) premiums for children in the highest
      program income eligibility categories. In this paper we compare the responses of
      SCHIP recipients in a state (Kentucky) that introduced SCHIP premiums for the
      first time at the end of 2003 with the responses of recipients in a state
      (Georgia) that increased existing SCHIP premiums in mid-2004. We start with a
      theoretical examination of how these different policies create different changes
      to family budget constraints and produce somewhat different financial incentives
      for recipients. Next we empirically model the impact of these policies using a
      competing risk approach to differentiate exits due to transfers to other
      eligibility categories of public coverage from exiting the public health
      insurance system. In both states we find a short-run increase in the likelihood
      that children transfer to lower- income eligibility/lower-premium categories of
      SCHIP. We also find a short-run increase in the rate at which children transfer
      from SCHIP to Medicaid in Kentucky, which is consistent with our theoretical
      model. These findings have important financial implications for state budgets, as
      the matching rates and premium levels are different for different eligibility
      categories of public coverage.

PMID- 19582700
TI  - A model to predict the cost-effectiveness of disease management programs.
AB  - High costs and deficits in the care of patients with chronic diseases have
      triggered numerous programs to improve the quality and efficiency of treatment of
      chronic diseases. Decision makers need to estimate the impact of a disease
      management program (DMP) on long-term costs and cost-effectiveness in order to
      decide which programs to introduce. This prediction, however, requires
      formalizing the relations between a variety of variables. The purpose of this
      paper is to formalize these relations and develop a model that enhances the
      quality of predictions of the costs and cost-effectiveness of a DMP. The model's
      cost function is able to portray a reduction both of treatment overuse and
      underuse by improving both physician and patient compliance. The model's
      applicability is demonstrated by a simulated DMP for patients with hypertension.
      The application example shows that implementation costs may have a larger
      financial impact than downstream costs.

PMID- 19582699
TI  - Adolescent depression and educational attainment: results using sibling fixed
      effects.
AB  - This paper contributes to the literature on the relationship between adolescent
      depression and educational attainment in several ways. First, while cross
      sectional data are normally used, this paper uses longitudinal data in order to
      defend against the potential of reverse causality. Second, this is the first
      paper in the literature to control for sibling-fixed effects in examining the
      relationship between adolescent depressive symptoms and human capital
      accumulation. Importantly, this eliminates omitted factors such as family and
      neighborhood characteristics common to siblings that affect both depressive
      symptoms and educational attainments (e.g. neighborhood crime, and family
      resources). Third, this paper examines the effects of both an indicator and scale
      of depressive symptoms and finds important associations with these depressive
      symptoms and human capital accumulation. Though the results cannot be given a
      causal interpretation, the findings show a negative relationship between
      depressive symptoms and years of schooling. The relationship appears to be driven
      primarily through increasing the chances of dropping out but may have small
      impacts on the likelihood of college attendance (conditional on high school
      graduation). In particular, preferred estimates suggest that a standard deviation
      increase in depressive symptoms is associated with a 25-30% increase in the
      likelihood of dropping out.

PMID- 19582701
TI  - Does the combination of fronto-maxillary facial angle and nasal bone evaluation
      improve the detection of Down syndrome in the second trimester?
AB  - OBJECTIVE: To determine if the combination of fronto-maxillary facial (FMF) angle
      and nasal bone (NB) evaluation improves the detection of Down syndrome (DS) in
      the second trimester. STUDY DESIGN: We compared the FMF angle measurements in
      euploid and DS fetuses seen between 2005 and 2008. The FMF angles were measured
      from stored two-dimensional (2-D) images by investigators blinded to the DS
      status of the fetus. All NB measurements were obtained prospectively. Receiver
      operator characteristic curve plot was used to determine the optimal definition
      for abnormal FMF angle. The detection and false positive rates and likelihood
      ratios positive and negative for the DS markers and their combinations were
      compared. RESULTS: Of 22 fetuses with DS seen between 16 and 22 weeks over the
      study period, NB and FMF angle evaluation was available for 21. These were
      compared with a control group of 201 fetuses seen at similar gestational age
      ranges without DS. NB alone identified 10/21 (47.6%) of Down syndrome while FMF
      angle identified 2/21 (9.5%). The combination of FMF angle and NB identified only
      one additional case of Down syndrome. CONCLUSIONS: While FMF angle and NB are
      independent markers for DS, their combination resulted in a minimal but
      nonsignificant improvement in DS detection.

PMID- 19582704
TI  - Bioanalysis 2009. Editorial.

PMID- 19582702
TI  - Decreased serum levels of kisspeptin in early pregnancy are associated with intra
      uterine growth restriction and pre-eclampsia.
AB  - OBJECTIVE: To investigate whether pregnancies with development of subsequent pre
      eclampsia and intra-uterine growth restriction are associated with altered levels
      of kisspeptin in maternal serum in the second trimester. STUDY DESIGN:
      Retrospective case-control study of 16-20 week serum samples matched for duration
      of storage at -70 degrees C. Levels of kisspeptin were measured in serum from
      women with pregnancies with subsequent development of pre-eclampsia (n = 57),
      intra-uterine growth restriction (n = 118), and matched controls (n = 317).
      RESULTS: Serum kisspeptin levels were significantly lower in those women who
      subsequently developed pre-eclampsia than in controls [median (quartile range)
      1109 (449) vs 1188 (365) pg/mL, p = 0.029] and in those with intra-uterine growth
      restriction [1164 (386) vs 1188 (365) pg/mL, p = 0.016]. CONCLUSIONS: Kisspeptin
      levels are lower in maternal serum in the second trimester, in pregnancies
      associated with placental dysfunction. The differences in kisspeptin are modest,
      so although not forming a single screening marker in pre-eclampsia and intra
      uterine growth restriction, measurement of kisspeptin may be useful in
      combination with other markers. Understanding the role of kisspeptin in the
      establishment of the placenta may further our knowledge of the mechanisms
      underlying placental function.

PMID- 19582706
TI  - Nanostructured pillars based on vertically aligned carbon nanotubes as the
      stationary phase in micro-CEC.
AB  - We present a micro-CEC chip carrying out a highly efficient separation of dsDNA
      fragments through vertically aligned multi-wall carbon nanotubes (MWCNTs) in a
      microchannel. The vertically aligned MWCNTs were grown directly in the
      microchannel to form straight nanopillar arrays as ordered and directional
      chromatographic supports. 1-Pyrenedodecanoic acid was employed for the surface
      modification of the MWCNTs' stationary phase to adsorb analytes by hydrophobic
      interactions. This device was used for separating dsDNA fragments of three
      different lengths (254, 360, and 572 bp), and fluorescence detection was employed
      to verify the electrokinetic transport in the MWCNT array. The micro-CEC
      separation of the three compounds was achieved in less than 300 s at a field
      strength of 66 V/cm due to superior laminar flow patterns and a lower flow
      resistance resulting from the vertically aligned MWCNTs being used as the
      stationary phase medium. In addition, a fivefold reduction of band broadening was
      obtained when the analyte was separated by the chromatographic MWCNT array
      channel instead of the CE channel. From all of the results, we suggest that an in
      situ grown and directional MWCNT array can potentially be useful for preparing
      more diversified forms of stationary phases for vertically efficient chip-based
      electrochromatography.

PMID- 19582707
TI  - Protein attachment onto silica surfaces--a survey of molecular fundamentals,
      resulting effects and novel preventive strategies in CE.
AB  - This review addresses the fundamentals governing the adsorption of individual
      protein molecules onto the surface of fused-silica capillaries, the protein
      aggregation to adsorbate clusters and their final accretion to monolayers with
      subsequent stratification to protein multilayers. The attention in CE protein
      separation has primarily been focused on (i) tuning the BGE including the buffer
      type, ionic strength, pH and additives, (ii) tailored post-rinse procedures to
      detach adhered protein residues and (iii) the optimization of capillary wall
      shielding in order to reduce protein attachment. Improvements in protein
      separation as well as related adverse effects are mainly discussed on the basis
      of parameters known to become deteriorated in case of protein adhesion, e.g.
      repeatability of the EOF and of migration times, peak width, theoretical plate
      numbers, resolution and asymmetry factor. However, knowledge of the molecular
      principles controlling protein adsorption onto silica surfaces is indispensable
      for separation optimization. Furthermore, it facilitates troubleshooting and the
      interpretation of undesired concomitant phenomena. This review comprehensively
      discusses protein adsorption models derived from surface chemistry primarily in
      terms of their relevance for CE, clearly showing that the adsorption process in
      its complexity is only partially revealed by models, which address single or
      binary protein solutions. In a further section theoretical concepts and surface
      models are related to surface phenomena encountered in CE. The final part of the
      review surveys recent concepts for prevention of protein adhesion, thereby
      addressing capillary treatment, favorable buffer types, dynamic and adhesive semi
      permanent coating strategies covering the literature from 2000-2008.

PMID- 19582705
TI  - DNA migration mechanism analyses for applications in capillary and microchip
      electrophoresis.
AB  - In 2009, electrophoretically driven DNA separations in slab gels and capillaries
      have the sepia tones of an old-fashioned technology in the eyes of many, even
      while they remain ubiquitously used, fill a unique niche, and arguably have yet
      to reach their full potential. For comic relief, what is old becomes new again:
      agarose slab gel separations are used to prepare DNA samples for "next-gen"
      sequencing platforms (e.g. the Illumina and 454 machines) - dsDNA molecules
      within a certain size range are "cut out" of a gel and recovered for subsequent
      "massively parallel" pyrosequencing. In this review, we give a Barron lab
      perspective on how our comprehension of DNA migration mechanisms in
      electrophoresis has evolved, since the first reports of DNA separations by CE (
      approximately 1989) until now, 20 years later. Fused-silica capillaries and
      borosilicate glass and plastic microchips quietly offer increasing capacities for
      fast (and even "ultra-fast"), efficient DNA separations. While the channel-by
      channel scaling of both old and new electrophoresis platforms provides key
      flexibility, it requires each unique DNA sample to be prepared in its own micro
      or nanovolume. This Achilles' heel of electrophoresis technologies left an
      opening through which pooled sample, next-gen DNA sequencing technologies rushed.
      We shall see, over time, whether sharpening understanding of transitions in DNA
      migration modes in crosslinked gels, nanogel solutions, and uncrosslinked polymer
      solutions will allow electrophoretic DNA analysis technologies to flower again.
      Microchannel electrophoresis, after a quiet period of metamorphosis, may emerge
      sleeker and more powerful, to claim its own important niche applications.

PMID- 19582708
TI  - Current separation and detection methods in microdialysis the drive towards
      sensitivity and speed.
AB  - This review outlines some of the analytical challenges associated with the
      analysis of microdialysis (MD) samples, in particular, the minute complex sample
      volumes that are often encountered. In MD sampling many different low-molecular
      weight molecules can be collected, but the research findings are often limited by
      the sensitivity, specificity, and reliability of the analytical technique that is
      coupled to the dialysis probe. Therefore it is critical that a lot of
      consideration is given in selecting the most suitable analytical method including
      the most appropriate detector. This review aims to highlight the strengths and
      weaknesses of a range of commonly used analytical methods employed in MD. In
      Section 1, a brief overview of the MD technique is described, followed by a
      discussion on some of the advantages and drawbacks of this sampling technique.
      Sections 2 and 3 examine analytical and other technical considerations regarding
      analysis, with special emphasis on the factors that specifically influence
      analytical detection. Section 4 outlines the most commonly employed analytical
      techniques used in MD, including HPLC coupled with various detectors. Detail is
      given regarding the LOD and LOQ for many applications using each detector. As MS
      is of such high importance in MD, a special sub-section has been devoted to it.
      The importance of CE is also highlighted, with specific applications described.
      In addition, analytical techniques that do not appear to have found routine use
      in MD are discussed. Section 5 is concerned with recent innovations in chemical
      separation techniques, in particular MCE and ultra-performance liquid
      chromatography. Specific applications of the coupling of these techniques with MD
      are highlighted, along with technical challenges associated with miniaturization.
      In the Section 6, the future outlook of MD is discussed. Techniques other than
      electrophoretic- and chromatographic based separation methods are outside the
      scope of this review.

PMID- 19582709
TI  - Introducing the CPL/MUW proteome database: interpretation of human liver and
      liver cancer proteome profiles by referring to isolated primary cells.
AB  - Interpretation of proteome data with a focus on biomarker discovery largely
      relies on comparative proteome analyses. Here, we introduce a database-assisted
      interpretation strategy based on proteome profiles of primary cells. Both 2-D
      PAGE and shotgun proteomics are applied. We obtain high data concordance with
      these two different techniques. When applying mass analysis of tryptic spot
      digests from 2-D gels of cytoplasmic fractions, we typically identify several
      hundred proteins. Using the same protein fractions, we usually identify more than
      thousand proteins by shotgun proteomics. The data consistency obtained when
      comparing these independent data sets exceeds 99% of the proteins identified in
      the 2-D gels. Many characteristic differences in protein expression of different
      cells can thus be independently confirmed. Our self-designed SQL database
      (CPL/MUW - database of the Clinical Proteomics Laboratories at the Medical
      University of Vienna accessible via www.meduniwien.ac.at/proteomics/database)
      facilitates (i) quality management of protein identification data, which are
      based on MS, (ii) the detection of cell type-specific proteins and (iii) of
      molecular signatures of specific functional cell states. Here, we demonstrate,
      how the interpretation of proteome profiles obtained from human liver tissue and
      hepatocellular carcinoma tissue is assisted by the Clinical Proteomics
      Laboratories at the Medical University of Vienna-database. Therefore, we suggest
      that the use of reference experiments supported by a tailored database may
      substantially facilitate data interpretation of proteome profiling experiments.

PMID- 19582710
TI  - CE of dsDNA in low-molecular-weight polyethylene oxide solutions.
AB  - To realise effective size separations of nucleic acid fragments using CE, gel
      based matrices are commonly employed. The separation of label-free dsDNA ladders
      and plasmid fragments in an uncross-linked semi-dilute poly (ethylene) oxide
      solution using multi-pixel UV detection at 254 nm is reported. Improvements in
      the sensitivity of UV detection of dsDNA using signal averaging over multiple
      pixels is demonstrated. Separations performed using a diode array detector also
      allow the progress of the separation to be monitored as a function of time.
      Several polymers were examined including methyl cellulose, linear polyacrylamide,
      hydroxy (propyl) methylcellulose and polyethylene oxide. Operations parameters
      investigated included UV transparency, self-coating capacity and separation
      efficiency. The results show complete resolution of all fragments under a range
      of conditions, including short separation lengths.

PMID- 19582712
TI  - Size-based protein separations by microchip electrophoresis using an acid-labile
      surfactant as a replacement for SDS.
AB  - We demonstrate the use of an acid-labile surfactant (ALS) as a replacement for
      SDS for size-based protein separations in a microfluidic device. ALS is of
      interest to the proteomic field as it degrades at low pH and hence can be removed
      to reduce surfactant interference with down-stream MS. A range of SDS and ALS
      concentrations were tested as denaturants for microchip electrophoresis to
      investigate their effects on the separation of proteins from 18 to 116 kDa and to
      provide a suitable comparison between the two surfactants. The electrophoretic
      mobilities of the proteins were not significantly affected by the use of ALS
      instead of SDS. Protein separations with ALS are performed in less than 3 min,
      which is a significant decrease in the time compared with the previous ALS
      separations on a slab gel format. We also demonstrate the use of poly-N
      hydroxyethylacrylamide as a dynamic, hydrophilic chip channel coating that can be
      applied with a rapid and simple protocol for size-based protein separation. The
      results reported here could significantly decrease the time and increase the
      attainable level of automation and integration of the front-end protein
      fractionation required for "top-down" proteomics.

PMID- 19582711
TI  - Rapid recovery of DNA from agarose gel slices by coupling electroelution with
      monolithic SPE.
AB  - An amino silica monolithic column prepared by in situ polymerization of
      tetraethoxysilane and N-(beta-aminoethyl)-gamma-aminopropyltriethoxysilane was
      firstly applied to recover DNA from agarose gel slices by coupling electroelution
      with monolithic SPE. DNA was electroeluted from the agarose gel slices onto the
      amino silica monolithic column. The DNA adsorbed on this monolithic column was
      then recovered using sodium phosphate solution at pH 10. The whole recovery
      procedure could be completed within 10 min because the use of amino silica
      monolithic column accelerated the DNA capture and facilitated the DNA release.
      Electroelution conditions, such as buffer pH, buffer concentration and applied
      voltage, were online optimized. The average yield for herring sperm DNA, pBR 322
      DNA and lambda DNA recovered from 1.0% w/v agarose gel slices were 55+/-4, 50+/-6
      and 42+/-7% (n=3), respectively. The polymerase chain reaction performance of pGM
      plasmid recovered from agarose gel slices demonstrated that the method could
      provide high-quality DNA for downstream processes. The combination of
      electroelution with monolithic SPE allows a rapid, simple and efficient DNA
      recovery method. This technique is especially useful for applications that need
      to purify small starting amounts of DNA.

PMID- 19582713
TI  - Mimicking virus attachment to host cells employing liposomes: analysis by chip
      electrophoresis.
AB  - Electrophoresis on a chip increasingly replaces electrophoresis in the capillary
      format because of its speed and containment of the sample within a disposable
      cartridge. In this paper we demonstrate its utility in the analysis of the
      interaction between a virus and a liposome-anchored receptor, mimicking viral
      attachment to host cells. This became possible because detergents, obligatory
      constituents of the BGE for capillary electrophoretic separation of the virus,
      were not necessary in the chip format. Separations were carried out in sodium
      borate buffer, pH 8.3. Liposomes and virus were both labeled for laser-induced
      fluorescence detection at lambda(ex)/lambda(em) 630/680 nm. Free virus and virus
      receptor complexes were resolved from virus attached to receptor-decorated
      liposomes in the absence of additives or sieving matrices within about 30 s on
      commercially available microfluidic chips.

PMID- 19582714
TI  - Separation of acidic and basic proteins by CE with CTAB additive and its
      applications in peptide and protein profiling.
AB  - In this paper, we report a very simple but efficient cationic micellar CE method
      for protein analysis in complex samples without any modification for the
      capillary wall. It was found that increased concentration (>or=2 mM) of CTAB
      additive in electrophoretic buffer can effectively suppress the wall adsorption
      of both acidic and basic proteins. The separation was improved with buffer pH
      decreasing from 6.0 to 3.0. By using a buffer containing 2 mM CTAB at pH 3.0,
      nine proteins with a wide range of pI values (4.7-11.0) were separated within 9
      min with high efficiencies (>6 x 10(5) plates per meter) and good reproducibility
      (RSDs of migration time <0.8% for run-to-run assays) and recoveries (91.6
      119.0%). This method was successfully applied to the analysis of complex
      biological samples, including plasma and red blood cells. Most importantly, we
      demonstrate the proteomic applications of the proposed method, including the
      analysis of tryptic digests of BSA and crude protein extracts from Escherichia
      coli cells. With simplicity, high efficiency, and good reproducibility, this
      method is promising for protein analysis in complex samples and may find its
      place in the future proteomic research.

PMID- 19582715
TI  - Complete sequencing of GABAA receptor subunit beta 3 by a rapid technique
      following in-gel digestion of the protein.
AB  - Knowledge on complete sequences is pivotal to identify splice variants, generate
      specific antibodies and predict conformation. A simple analytical approach to
      obtain 100% sequence coverage, however, is currently not available. Recombinant
      gamma-aminobutyric acid A receptor subunits were from insect SF9 cells that were
      co-transfected with rat alpha1 and His-tag beta 3. The complex of these two
      subunits was run on blue-native PAGE, followed by multidimensional
      electrophoretic steps. Spots resolved at the third electrophoretic step were in
      gel digested with trypsin, chymotrypsin and Asp-N. In-gel modification of lysines
      by acetylation was carried out to increase sequence coverage. Subsequently,
      peptides were analyzed by nano-ESI-LC-MS/MS using both, collision-induced
      dissociation and electron transfer dissociation principles. When results from
      trypsin, chymotrypsin and Asp-N digestion were combined, a single peptide [424
      KKTHLRRRSSQL 435] was still not identified. In-gel lysine acetylation leads to
      unambiguous identification of this peptide by the use of MASCOT v2.2. The use of
      the Modiro software along with MASCOT, however, was able to provide 100% sequence
      coverage even without the use of in-gel lysine acetylation. It was observed that
      the use of trypsin, chymotrypsin and Asp-N with bioinformatic handling by the
      MASCOT and Modiro software is sufficient to obtain complete sequencing of a
      highly hydrophobic membrane protein.

PMID- 19582716
TI  - Fabrication of a microfluidic enzyme reactor utilizing magnetic beads.
AB  - An enzyme-catalyzed microfluidic assay using magnetic micro-beads is described.
      Here, diaphorase (DI) (E.C. 1.6.99) is covalently attached to the magnetic micro
      beads (2.7 mum) and integrated into a short section of a microchip fabricated
      from PDMS. DI converts non-fluorescent resazurin to fluorescent resorufin in the
      presence of nicotinamide adenine dinucleotide phosphate (NADH). In this work, an
      embedded magnet holds the micro-beads in place within the microchannel while a
      solution of resazurin and NADH in buffer is flowed through the beads.
      Incorporation of the micro-beads into the microchannel requires only a few
      minutes and offers well-defined spatial resolution and reproducibility. At a flow
      rate of 41.2 microL/h, a stable state for the enzyme reaction in the microfluidic
      format was achieved within 50 s. The maximum conversion of the reaction was
      obtained at a concentration of 1.25 mM NADH. The reaction yield is affected by
      ZnCl(2) and at concentrations in excess of 90.0 mM, the activity of DI was almost
      double without ZnCl(2). At 5.2 mM potassium chloride, the activity of DI reached
      its maximum value. Overall, the conversion of resazurin in microfluidic format
      was more than twice than that in a batch assay.

PMID- 19582717
TI  - Characterization and identification of proteases secreted by Aspergillus
      fumigatus using free flow electrophoresis and MS.
AB  - Early diagnosis of life-threatening invasive aspergillosis in neutropenic
      patients remains challenging because current laboratory methods have limited
      diagnostic sensitivity and/or specificity. Aspergillus species are known to
      secrete various pathogenetically relevant proteases and the monitoring of their
      protease activity in serum specimens might serve as a new diagnostic approach.For
      the characterization and identification of secreted proteases, the culture
      supernatant of Aspergillus fumigatus was fractionated using free flow
      electrophoresis (Becton Dickinson). Protease activity of separated fractions was
      measured using fluorescently labeled reporter peptides. Fractions were also co
      incubated in parallel with various protease inhibitors that specifically inhibit
      a distinct class of proteases e.g. metallo- or cysteine-proteases. Those
      fractions with high protease activity were further subjected to LC-MS/MS analysis
      for protease identification. The highest protease activity was measured in
      fractions with an acidic pH range. The results of the 'inhibitor-panel' gave a
      clear indication that it is mainly metallo- and serine-proteases that are
      involved in the degradation of reporter peptides. Furthermore, several proteases
      were identified that facilitate the optimization of reporter peptides for
      functional protease profiling as a diagnostic tool for invasive aspergillosis.

PMID- 19582718
TI  - Detection of autoantibodies against cyclophilin A and triosephosphate isomerase
      in sera from breast cancer patients by proteomic analysis.
AB  - Much interest is presently being shown toward identifying markers for the
      detection of breast cancer. To detect autoantibodies that could represent
      diagnostic markers for breast cancer, we comprehensively analyzed serum
      autoantibodies showing immunoreactivity to proteins in tumor tissues of breast
      cancer. Tumor tissues were obtained from 40 patients with breast cancer, along
      with sera from 30 other patients with breast cancer and 22 healthy donors.
      Proteins from tumor tissues were separated by 2-DE. After blotting onto PVDF
      membranes, tissue proteins were immunoblotted with sera from patients or healthy
      donors. By comparing each immunoblot pattern, three immunoreactive spots
      displayed stronger staining intensity with patient sera than with sera from
      healthy donors. The matched protein spots on 2-DE gels were digested and used for
      LC-MS/MS analysis, and identified as cyclophilin A (peptidyl-prolyl cis-trans
      isomerase A), triosephosphate isomerase and ubiquitin-conjugating enzyme E2N.
      Immunoblot analysis was then performed using commercially available purified
      proteins, confirming the specificity of anti-cyclophilin A and anti
      triosephosphate isomerase antibodies in sera from patients.

PMID- 19582719
TI  - Upregulation of glycolytic enzymes in proteins secreted from human colon cancer
      cells with 5-fluorouracil resistance.
AB  - 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for
      colorectal cancer (CRC). However, resistance to this drug is a major obstacle in
      CRC chemotherapy. Accurate prediction of response to 5-FU would avoid unnecessary
      chemotherapy and allow the selection of other effective drugs. To identify a
      candidate predictor of 5-FU resistance, we isolated secreted proteins that were
      up- or downregulated in a 5-FU-resistant cancer cell line, compared with the
      parent cell line (SNU-C4), using a stable isotope-coded labeling protocol. For
      validating the clinical applicability of this method, levels of the identified
      proteins were determined in the sera of 46 patients treated with 5-FU. In total,
      238 proteins with molecular weights ranging from 50 to 75 kDa were identified.
      Among these, 45 and 35 secreted proteins were up- and downregulated in the 5-FU
      resistant cell line, respectively. We observed significant upregulation of
      glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate
      kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1. In
      particular, the level of PK-M2, a key enzyme in the glycolytic pathway, showed an
      increasing tendency in both sera and tissues from CRC patients displaying no
      response to 5-FU-based chemotherapy (progressive and stable disease cases),
      compared with that in complete or partial responders to 5-FU-based chemotherapy;
      however, it did not reach the statistical significance. In conclusion, increasing
      pattern of PK-M2 observed with 5-FU resistance induced in vitro and in sera and
      tissues from CRC patients displaying poor response to 5-FU-based chemotherapy
      suggest the relevance of dysregulated glycolysis and 5-FU-resistant CRC.

PMID- 19582720
TI  - Proteomic signature of reversine-treated murine fibroblasts by 2-D difference gel
      electrophoresis and MS: possible associations with cell signalling networks.
AB  - Recent advances in stem cell biology have demonstrated that terminally
      differentiated adult cells can be induced to de-differentiate into progenitor
      cells (induced stem cells) upon proper stimuli. This has been achieved by the
      induced expression of key regulatory genes by retro- or lenti-viral systems. On
      the other hand, synthetic "small molecules" can also induce de-differentiation
      and may represent a potentially safer approach as compared with genetic
      manipulation. Along this line, a synthetic purine called "reversine" has been
      shown to induce the de-differentiation of fibroblasts into mesenchymal stem-cell
      like progenitors, which can be successively induced to differentiate into
      skeletal muscle, smooth muscle and bone cells. The mechanism whereby reversine is
      able to achieve de-differentiation has yet to be clarified. In this context, we
      defined the protein changes induced by reversine treatment in murine fibroblasts
      by 2-D difference gel electrophoresis, coupled with MS. Proteins involved in
      cytoskeletal and cell shape remodeling, RNA export, degradation, folding, stress
      control and ATP production were found to be remarkably changed after reversine
      treatment. Ingenuity pathway analysis (IPA) predicted that these protein pattern
      changes enabled to propose that about 40 proteins might be associated to several
      biological functional networks, including cellular assembly, cell signaling and
      cell death. Altogether our data confirm the intrinsic complexity of the de
      differentiation process induced by reversine and suggest more selected approaches
      to investigate the action mechanism of this small molecule.

PMID- 19582722
TI  - Development of a 2-D apoB peptide profile to detect conformational changes
      associated with apoB-containing lipoproteins.
AB  - PTMs, such as glycosylation and phosphorylation of apolipoprotein B100 (apoB),
      are known to be involved with modulating the metabolism of apoB-containing
      lipoproteins. Current evidence suggests that intracellular and extracellular PTM
      of apoB are associated with various disorders such diabetes, dyslipidemia and
      atherosclerosis. The ability to identify and characterize the specific PTM of
      apoB correlating to specific pathologies may improve our understanding of the
      underlying molecular mechanisms regulating apoB metabolism. We have developed an
      assay to detect PTM and/or conformational changes in apoB isolated from the media
      of HepG2 cells. Using trypsin digestion in conjunction with 2-DE and Western
      blotting, a 2-D peptide fragment profile of apoB was established. The 2-D apoB
      profile was composed of a number of trypsin-generated fragments having a
      molecular mass between 10 and 188 kDa and a wide spectrum of isoelectric points.
      The 2-D apoB profile obtained from the media of HepG2 cells treated in the
      presence of agents (tunicamycin and glucosamine) known to modulate the PTM of
      apoB was distinct from that of control cells. Identifying changes in the 2-D apoB
      profile has the potential to not only provide insight into the underlying
      mechanisms regulating the metabolism of apoB-containing lipoproteins but may also
      have important implications for the development of novel diagnostic tools and/or
      future therapeutic agents.

PMID- 19582724
TI  - Simple method for determination of cocaine and main metabolites in urine by CE
      coupled to MS.
AB  - In this work, a simple method for the simultaneous determination of cocaine (COC)
      and five COC metabolites (benzoylecgonine, cocaethylene (CET), anhydroecgonine,
      anhydroecgonine methyl ester and ecgonine methyl ester) in human urine using CE
      coupled to MS via electrospray ionization (CE-ESI-MS) was developed and
      validated. Formic acid at 1 mol/L concentration was used as electrolyte whereas
      formic acid at 0.05 mol/L concentration in 1:1 methanol:water composed the
      coaxial sheath liquid at the ESI nozzle. The developed method presented good
      linearity in the dynamic range from 250 ng/mL to 5000 ng/mL (coefficient of
      determination greater than 0.98 for all compounds). LODs (signal-to-noise ratio
      of 3) were 100 ng/mL for COC and CET and 250 ng/mL for the other studied
      metabolites whereas LOQ's (signal-to-noise ratio of 10) were 250 ng/mL for COC
      and CET and 500 ng/mL for all other compounds. Intra-day precision and recovery
      tests estimated at three different concentration levels (500, 1500 and 5000
      ng/mL) provided RSD lower than 10% (except anhydroecgonine, 18% RSD) and
      recoveries from 83-109% for all analytes. The method was successfully applied to
      real cases. For the positive urine samples, the presence of COC and its
      metabolites was further confirmed by MS/MS experiments.

PMID- 19582723
TI  - The identification of phosphoglycerate kinase-1 and histone H4 autoantibodies in
      pancreatic cancer patient serum using a natural protein microarray.
AB  - Protein microarrays have been used to explore whether a humoral response to
      pancreatic cancer-specific tumor antigens has utility as a biomarker of
      pancreatic cancer. To determine if such arrays can be used to identify novel
      autoantibodies in the sera from pancreatic cancer patients, proteins from a
      pancreatic adenocarcinoma cell line (MIAPACA) were resolved by 2-D liquid-based
      separations, and then arrayed on nitrocellulose slides. The slides were probed
      with serum from a set of patients diagnosed with pancreatic cancer and compared
      with age- and sex-matched normal subjects. To account for patient-to-patient
      variability, we used a rank-based non-parametric statistical testing approach in
      which proteins eliciting significant differences in the humoral response in
      cancer compared with control samples were identified. The prediction analysis for
      microarrays classification algorithm was used to explore the classification power
      of the proteins found to be differentially expressed in cancer and control sera.
      The generalization error of the classification analysis was estimated using leave
      one-out cross-validation. A serum diagnosis of pancreatic cancer in this set was
      predicted with 86.7% accuracy, with a sensitivity and specificity of 93.3 and
      80%, respectively. Candidate autoantibody biomarkers identified using this
      approach were studied for their classification power by performing a humoral
      response experiment on recombinant proteins using an independent sample set of
      238 serum samples. Phosphoglycerate kinase-1 and histone H4 were noted to elicit
      a significant differential humoral response in cancer sera compared with age- and
      sex-matched sera from normal patients and patients with chronic pancreatitis and
      diabetes. This work demonstrates the use of natural protein arrays to study the
      humoral response as a means to search for the potential markers of cancer in
      serum.

PMID- 19582725
TI  - The new framework for understanding placental mammal evolution.
AB  - An unprecedented level of confidence has recently crystallized around a new
      hypothesis of how living placental mammals share a pattern of common descent. The
      major groups are afrotheres (e.g., aardvarks, elephants), xenarthrans (e.g.,
      anteaters, sloths), laurasiatheres (e.g., horses, shrews), and euarchontoglires
      (e.g., humans, rodents). Compared with previous hypotheses this tree is
      remarkably stable; however, some uncertainty persists about the location of the
      placental root, and (for example) the position of bats within laurasiatheres, of
      sea cows and aardvarks within afrotheres, and of dermopterans within
      euarchontoglires. A variety of names for sub-clades within the new placental
      mammal tree have been proposed, not all of which follow conventions regarding
      priority and stability. More importantly, the new phylogenetic framework enables
      the formulation of new hypotheses and testing thereof, for example regarding the
      possible developmental dichotomy that seems to distinguish members of the newly
      identified southern and northern radiations of living placental mammals.

PMID- 19582726
TI  - Water-soluble DNA-wrapped single-walled carbon-nanotube/quantum-dot complexes.

PMID- 19582727
TI  - Salt rejection and water transport through boron nitride nanotubes.
AB  - Nanotube-based water-purification devices have the potential to transform the
      field of desalination and demineralization through their ability to remove salts
      and heavy metals without significantly affecting the fast flow of water
      molecules. Boron nitride nanotubes have shown superior water flow properties
      compared to carbon nanotubes, and are thus expected to provide a more efficient
      water purification device. Using molecular dynamics simulations it is shown that
      a (5, 5) boron nitride nanotube embedded in a silicon nitride membrane can, in
      principle, obtain 100% salt rejection at concentrations as high as 1 M owing to a
      high energy barrier while still allowing water molecules to flow at a rate as
      high as 10.7 water molecules per nanosecond (or 0.9268 L m(-2) h(-1)).
      Furthermore, ions continue to be rejected under the influence of high hydrostatic
      pressures up to 612 MPa. When the nanotube radius is increased to 4.14 A the tube
      becomes cation-selective, and at 5.52 A the tube becomes anion-selective.

PMID- 19582728
TI  - Design and characterization of rotational multicomponent catalytic nanomotors.
AB  - Multicomponent rotational nanomotors consisting of Pt-coated TiO(2) nanoarms
      grown upon approximately 2.01-microm-diameter silica microbeads designed by
      dynamic shadowing growth are presented. When exposed to H(2)O(2), the structures
      rotate about an axis through the center of the microbead and perpendicular to the
      TiO(2) nanoarm at a rate of 0.15 Hz per % H(2)O(2) concentration. The rotational
      frequency increases parabolically when the surface tension of the solution is
      altered by the addition of sodium dodecyl sulphate; both relationships are
      explainable by a nanobubble-ejection model.

PMID- 19582730
TI  - A facile and novel synthesis of Ag-graphene-based nanocomposites.

PMID- 19582729
TI  - Direct growth of ZnO nanocrystals onto the surface of porous TiO(2) nanotube
      arrays for highly efficient and recyclable photocatalysts.

PMID- 19582731
TI  - A modified micromolding method for sub-100-nm direct patterning of Pd nanowires.

PMID- 19582732
TI  - Intensity-carrying modes in Raman and Raman optical activity spectroscopy.
AB  - We describe a quantum-chemical approach for the determination of modes with
      maximum Raman and Raman optical activity (ROA) intensity by maximizing the
      intensities with respect to the Raman and Raman optical activity intensity,
      respectively, which is shown to lead to eigenvalue equations. The intensity
      carrying modes are in general hypothetical modes and do not directly correspond
      to a certain normal mode in the spectrum. However, they provide information about
      those molecular distortions leading to intense bands in the spectrum. Modes with
      maximum Raman intensity are presented for propane-1,3-dione, propane-1,3-dionate,
      and Lambda-tris(propane-1,3-dionato)cobalt(III). Moreover, the mode with highest
      ROA intensity is examined for this chiral cobalt complex and also for the
      (chiral) amino acid L-tryptophan. The Raman and ROA high-intensity modes are an
      optimal starting guess for intensity-tracking calculations, in which selectively
      normal modes with high Raman or ROA intensity are converged. We present the first
      Raman and ROA intensity-tracking calculations. These reveal a high potential for
      large molecules, for which the selective calculation of normal modes with high
      intensity is desirable in view of the large computational effort required for the
      calculation of Raman and ROA polarizability property tensors.

PMID- 19582735
TI  - "Ruggero ceppellini" advanced school of immunology.

PMID- 19582733
TI  - Hollow mesoporous carbon spheres with magnetic cores and their performance as
      separable bilirubin adsorbents.
AB  - Hollow mesoporous carbon spheres with magnetic cores are directly replicated from
      hollow mesoporous aluminosilicate spheres with hematite cores by a simple
      incipient-wetness impregnation technique. The amount of magnetic cores and the
      saturation magnetization value can be easily tuned by changing the concentration
      of iron nitrate solution used in the synthesis procedure. As-prepared hollow
      mesoporous carbon spheres with magnetic cores are used as separable bilirubin
      adsorbents and show very good adsorptive properties. The characteristics of as
      prepared composites are examined by XRD, N(2) sorption, TEM, vibrating-sample
      magnetometry, and UV/Vis spectroscopy.

PMID- 19582736
TI  - A roadmap for thymic epithelial cell development.
AB  - Thymic epithelial cells (TEC) are essential components of the thymus that guide
      and control the development and TCR repertoire selection of T cells. Previously,
      TEC have been considered as postmitotic cells that, once generated during
      ontogeny, were maintained in their mature state. Recently, it has become clear
      that TEC can be generated from common or committed medullary and cortical TEC
      progenitor cells in ontogeny, that stages of immature and mature TEC are
      phenotypically separable, and that TEC undergo a rapid turnover in a matter of a
      few weeks. All of these findings strongly suggest that in the adult thymus mature
      TEC are constantly regenerated from a pool of stem or progenitor cells, a view
      that renders the thymus structure potentially much more dynamic than previously
      thought. However, the identity of "thymus stem cells" is elusive, and
      developmental stages of TEC development are only beginning to be elucidated.

PMID- 19582737
TI  - CTL quality and the control of human retroviral infections.
AB  - The CTL response plays a central part in deciding the outcome of viral
      infections. Evidence from host and viral genetics, gene expression microarrays
      and assays of T-cell phenotype and function indicate that individual differences
      in the efficiency of the virus-specific CTL response strongly determine the
      outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now
      believed that differences in anti-viral CTL efficiency or "quality" at the single
      cell level are critical in determining the efficacy of the host response to
      viruses. However, it is difficult to identify and quantify the reasons for this
      apparent individual variation in CTL efficiency, because of the chronic course of
      infection and the dynamical complexity of the equilibrium that is established
      between the virus and the host immune response. Specifically, it is unclear
      whether the observed variations among infected hosts, i.e. in the frequency,
      phenotype and function or quality of T cells, are the causes or effects - or both
      - of the variation in the efficiency of virus control.

PMID- 19582738
TI  - Getting to the crux of the matter: IL-23 and Th17 cell accumulation in the CNS.
AB  - IL-23 plays a critical role in EAE induced by the active immunization of C57BL/6
      mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein
      (MOG(35-55)). It was initially assumed that the pathogenic effects of IL-23 were
      directly related to the generation, expansion and/or stabilization of
      autoreactive CD4(+) Th17 cells. However, a number of recent studies have
      uncovered discrepancies between the requirement for IL-23, as opposed to Th17
      cells or their products (IL-17A, IL-17F and IL-22), in the development of EAE. In
      this issue of the European Journal of Immunology, it is demonstrated that
      impairment of IL-23 signaling does not impede the expansion of myelin-specific
      CD4(+) T cells in peripheral lymphoid tissues but inhibits their accumulation in
      the CNS. This paper contributes to a growing body of data that implicates IL-23
      in the acquisition of CNS homing properties by autoreactive effector cells.

PMID- 19582740
TI  - Silver nanoparticles with broad multiband linear optical absorption.

PMID- 19582741
TI  - The two structures of the hexafluorobenzene radical cation C6F6(*+).

PMID- 19582739
TI  - Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II
      NKT cells.
AB  - The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) is a demonstrated ligand for
      a subset of CD1d-restricted NKT cells, which could regulate experimental
      autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as
      tumor immunity and experimental hepatitis. Native sulfatide is a mixture of
      sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and
      fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide
      specific CD1d-restricted murine NKT hybridomas recognized several different
      sulfatide isoforms. These included the physiologically relevant isoforms C24:1
      and C24:0, major constituents of the myelin sheet of the nervous system, and
      C16:0, prominent in the pancreatic islet beta-cells. The most potent sulfatide
      isoform was lysosulfatide (lacking a fatty acid). Shortened fatty acid chain
      length (C24:1 versus C18:1), or saturation of the long fatty acid (C24:0),
      resulted in reduced stimulatory capacity, and fatty acid hydroxylation abolished
      the response. Moreover, sulfatide was not responsible for the natural
      autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a
      promiscuity in the recognition of sulfatide isoforms by a CD1d-restricted NKT
      cell clone, and suggest that sulfatide, a major component of the myelin sheet and
      pancreatic beta-cells, is one of several natural ligands for type II CD1d
      restricted NKT cells.

PMID- 19582742
TI  - Making protein patterns by writing in a protein-repelling matrix.

PMID- 19582744
TI  - Copper-catalyzed alkylation of sulfonamides with alcohols.

PMID- 19582743
TI  - In situ assembly and screening of enzyme inhibitors with surface-tension
      microarrays.

PMID- 19582745
TI  - Light-triggered bioactivity in three dimensions.

PMID- 19582747
TI  - Triflic acid catalyzed synthesis of spirocycles via acetylene cations.

PMID- 19582746
TI  - Polystyrene sulfonyl chloride: a highly orthogonal linker resin for the synthesis
      of nitrogen-containing heterocycles.

PMID- 19582748
TI  - An efficient dye-sensitized solar cell with an organic sensitizer encapsulated in
      a cyclodextrin cavity.

PMID- 19582749
TI  - Supramolecular chemistry on a cluster surface: fixation/complexation of potassium
      and ammonium ions with crown-ether-like rings.

PMID- 19582750
TI  - Total spontaneous resolution of five-coordinate complexes.

PMID- 19582751
TI  - Building addressable libraries: site-selective Lewis acid (scandium(III))
      catalyzed reactions.

PMID- 19582752
TI  - Unzipping carbon nanotubes: a peeling method for the formation of graphene
      nanoribbons.

PMID- 19582753
TI  - Immunisation route-dependent expression of IL-4/IL-13 can modulate HIV-specific
      CD8(+) CTL avidity.
AB  - All HIV-1 'systemic vaccine trials' in humans have yielded poor outcomes. Thus,
      it is important to understand whether the route of delivery influences the
      quality of protective CTL immunity. Using heterologous poxvirus immunisation we
      have shown that systemically (i.m./i.m.) immunised CD8(+) T cells generated
      higher levels of IL-4/IL-13 compared to mucosal delivery and expression also
      correlated with i.m./i.m. immunised mice eliciting CTL of lower avidity. Studies
      using IL-4(-/-) and IL-13(-/-) KO mice have shown that the capacity to express
      IFN-gamma, IL-4 and/or IL-13 by K(d)Gag(197-205)-specific CTL differed between
      these groups and was inversely correlated with CTL avidity (IL-13(-/-)>IL-4(-/
      )>BALB/c), although no significant differences in the magnitude of CTL responses
      were observed between IL-13(-/-) and wild type mice. When IL-13 was reconstituted
      in IL-13(-/-) splenocytes in vitro, their ability to bind tetramers also
      decreased significantly. Our data reveal that total absence of IL-13 can greatly
      enhance CTL avidity. In contrast, extracellular IL-4 appears to be important in
      maintaining long-term Th1/Th2 balance in CTL, even though expression of IL-4 by
      CTL markedly reduced avidity. STAT6(-/-) mice also showed memory CTL of higher
      avidity. Furthermore, CCL5 expression in K(d)Gag(197-205)-specific CTL was also
      regulated by IL-4/IL-13.

PMID- 19582754
TI  - Hydration effects on skin microstructure as probed by high-resolution cryo
      scanning electron microscopy and mechanistic implications to enhanced
      transcutaneous delivery of biomacromolecules.
AB  - Although hydration is long known to improve the permeability of skin, penetration
      of macromolecules such as proteins is limited and the understanding of enhanced
      transport is based on empirical observations. This study uses high-resolution
      cryo-scanning electron microscopy to visualize microstructural changes in the
      stratum corneum (SC) and enable a mechanistic interpretation of biomacromolecule
      penetration through highly hydrated porcine skin. Swollen corneocytes, separation
      of lipid bilayers in the SC intercellular space to form cisternae, and networks
      of spherical particulates are observed in porcine skin tissue hydrated for a
      period of 4-10 h. This is explained through compaction of skin lipids when
      hydrated, a reversal in the conformational transition from unilamellar liposomes
      in lamellar granules to lamellae between keratinocytes when the SC skin barrier
      is initially established. Confocal microscopy studies show distinct enhancement
      in penetration of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA)
      through skin hydrated for 4-10 h, and limited penetration of FITC-BSA once skin
      is restored to its natively hydrated structure when exposed to the environment
      for 2-3 h. These results demonstrate the effectiveness of a 4-10 h hydration
      period to enhance transcutaneous penetration of large biomacromolecules without
      permanently damaging the skin.

PMID- 19582755
TI  - Caring for mom and neglecting yourself? The health effects of caring for an
      elderly parent.
AB  - We examine the physical and mental health effects of providing care to an elderly
      mother on the adult child caregiver. We address the endogeneity of the selection
      in and out of caregiving using an instrumental variable approach, using the death
      of the care recipient and sibling characteristics. We also carefully control for
      baseline health and work status of the adult child. We explore flexible
      specifications, such as Arellano-Bond estimation techniques. Continued caregiving
      over time increases depressive symptoms and decreases self-rated health for
      married women and married men. In addition, the increase in depressive symptoms
      is persistent for married women. While depressive symptoms for single men and
      women are not affected by continued caregiving, there is evidence of increased
      incidence of heart conditions for single men, and that these effects are
      persistent. Robustness checks indicate that these health changes can be directly
      attributable to caregiving behavior, and not due to a direct effect of the death
      of the mother. The initial onset of caregiving has modest immediate negative
      effects on depressive symptoms for married women and no immediate effects on
      physical health. Negative physical health effects emerge 2 years later, however,
      suggesting that there are delayed effects on health that would be missed with a
      short recall period. Initial caregiving does not affect health of married men.

PMID- 19582756
TI  - Brief cognitive screening instruments: an update.
AB  - OBJECTIVE: To review the recent literature on cognitive screening with a focus on
      brief screening methods in primary care as well as geriatric services. DESIGN:
      The Medline search engine was utilized using the keyword search terms 'cognitive
      screening', 'cognitive assessment', and 'dementia screening' limiting articles to
      those published in English since 1998. RESULTS: 679 abstracts were retrieved.
      Articles focusing on attitudes toward cognitive screening, current screening
      practices, promising new instruments and more recent updates contributing
      significant information on established instruments were retrieved and
      incorporated into this review. Reference lists were reviewed for relevant
      contributing articles. Instruments recommended from previous reviews of cognitive
      screening and those identified in surveys as most frequently used in primary care
      and geriatric settings were emphasized in this review. CONCLUSIONS: Dementia
      remains under-diagnosed in the elderly population. Despite significant
      limitations, the Mini Mental State Exam remains the most frequently used
      cognitive screening instrument. Its best value in the community and primary care
      appears to be for the purpose of ruling out a diagnosis of dementia. Instruments
      such as the Mini-Cog, Memory Impairment Screen (MIS), and the General
      Practitioner Assessment of Cognition (GPCOG) have consistently been recognized
      for utility in primary care. The clock drawing test (CDT) and newer instruments
      such as the Montreal Cognitive Assessment (MoCA) and the Rowland Universal
      Dementia Assessment Scale (RUDAS) are gaining credibility due to improvements in
      sensitivity, addressing frontal/executive functioning, and decreasing
      susceptibility to cultural and educational biases.

PMID- 19582757
TI  - Effectiveness of an individualized functional training program on affective
      disturbances and functional skills in mild and moderate dementia--a randomized
      control trial.
AB  - OBJECTIVES: We reported the findings of a randomized controlled trial (RCT) to
      examine the effects of an individualized functional enhancement program (FEP) on
      functional skills and mood symptoms in mild and moderate dementia. SUBJECTS &
      METHODS: 74 Chinese older persons with dementia were recruited into a skills
      training program by occupational therapists (OT). Thirty seven subjects were
      trained with an individualized selection of daily activities (FEP Intervention,
      I); 37 were trained with general occupational therapy (Control, C). The FEP
      comprised of twice weekly group sessions of skills training and problem solving
      using cognitive behavioral approach. RESULTS: At 1 month after completion of
      program, both I and C subjects showed an improvement in process skills of the
      assessment of motor and process skills (AMPS)(paired t-tests, p < 0.05). At 4
      months post-program, the I group showed a further reduction of cornell scale for
      depression in dementia (CSDD) scores (paired t-test, p = 0.02); Apathy improved
      at 1 month post-training (p = 0.04), but deteriorated at 4 months (p = 0.01).
      Group differences in changes of mood and functional scores were not significant
      (ANVOCA, p > 0.05). CONCLUSIONS: The findings suggested a potential benefit for
      individualized occupational therapy. It should be tailor made with individual
      needs and continued for sustained effectiveness.

PMID- 19582758
TI  - Health status and suicide in the second half of life.
AB  - OBJECTIVE: To examine the associations of suicide in the second half of life with
      medical and psychiatric illness, functional limitations, and reported use of
      inpatient, ambulatory, and home health care services. METHOD: A retrospective
      case-control design was used to compare 86 people over age 50 years who died by
      suicide with a comparison group of 86 living community participants that were
      individually matched on age, gender, race, and county of residence. RESULTS:
      Suicide decedents had more Axis I diagnoses, including current mood and anxiety
      disorders, worse physical health status, and greater impairment in functional
      capacity. They were more likely to have required psychiatric treatment, medical,
      or surgical hospitalization in the last year, and visiting nurse or home health
      aide services. In a multivariate model, the presence of any active Axis I
      disorder and any impairment in instrumental activities of daily living (IADL)
      made independent contributions to suicide risk. CONCLUSIONS: Mental illness,
      physical illness, and associated functional impairments represent domains of risk
      for suicide in this age group. In addition to individuals with psychiatric
      illness, those with severe or comorbid physical illness and functional disability
      who require inpatient and home care services should be targeted for screening and
      preventive interventions.

PMID- 19582759
TI  - Subjective sleep, depression and anxiety: inter-relationships in a non-clinical
      sample.
AB  - OBJECTIVES: Previous research confirms the interdependent relationship between
      poor sleep and depression, but has often focused on objective measures of sleep
      and overlooked the importance of subjective factors. Insomnia may be maintained
      by anxiety and perceptions of poor sleep timing, and depression is associated
      with poor sleep satisfaction, regardless of perceived sleep timing. METHODS: This
      study explored the contribution of current depression and anxiety to sleep
      perceptions. Participants (n = 98) completed the Hospital Anxiety and Depression
      scale, and questionnaires were used to evaluate current and previous psychiatric
      illness, sleep disorders and prescribed psychotropic medication. RESULTS: A
      series of ANOVAs and regression analyses indicated that variance in sleep timing
      perceptions was more likely to be explained by symptoms of anxiety than
      depression; explained variance (adj. R(2)) 25%, t = 2.361; p = 0.023. The
      analyses also showed that sleep satisfaction perceptions (adj. R(2) = 20%, t =
      3.085; p = 0.004), and those relating to overall quality of life (adj. R(2) =
      37%, t = -2.763; p = 0.013), were more likely to be explained by symptoms of
      depression. CONCLUSIONS: These findings support the observation that anxiety
      appears related to poorer sleep timing perceptions, while depression appears
      associated with poor sleep satisfaction. Further research is needed to explore
      the factors that might maintain poor sleep satisfaction in depression.

PMID- 19582760
TI  - Pilot study of a three-step diagnostic pathway for young and old patients with
      Parkinson's disease dementia: screen, test and then diagnose.
AB  - OBJECTIVE: To pilot a three-step diagnostic model for young and old patients with
      Parkinson's disease dementia (PDD). METHODS: Prospective investigator-blinded
      study. We developed a screening questionnaire for patients with Parkinson's
      disease (PD) and their caregivers. Further, patients were subjected to three
      screening instruments (Montreal Cognitive Assessment (MoCA), Frontal Assessment
      Battery (FAB), Addenbrooke's Cognitive Examination-revised (ACE-R) and a detailed
      neuropsychological examination (NPE). Based on the NPE, patients were divided in
      a PD (without dementia) and a PDD-group. RESULTS: Forty-one PD patients, aged 37
      94 years, participated in this study. Patients were divided in a young group, <
      or = 65 (n = 22) and an old group >65 years (n = 19). In the young group (PDD, n
      = 5) the patient-screening questionnaire predicted PDD with a
      sensitivity/specificity of 100.0%/94.1%; in the old group (PDD, n = 10) the proxy
      screening questionnaire predicted PDD with a sensitivity/specificity of
      88.9%/66.7%. In the young group, ACE-R had the largest Area Under the Curve (AUC)
      0.88 (0.70-1.00), in the old group MoCA (AUC 1.00). However, the three
      instruments did not differ significantly. CONCLUSIONS: It seems feasible and
      efficient to use three consecutive diagnostic steps for PDD: (1) a screening
      questionnaire, (2) if positive: MoCA, FAB or ACE-R as screening instrument and
      (3) if positive: a detailed NPE for diagnosing PDD.

PMID- 19582762
TI  - Insulin-like growth factor type I receptor gene expression and obesity in
      esophageal adenocarcinoma.
AB  - The objective of this exploratory study was to evaluate the role of the insulin
      like growth factor I receptor (IGF-IR) in esophageal adenocarcinoma (EADC). Using
      quantitative PCR, we studied IGF-IR mRNA expression in 52 well-characterized
      surgically resected EADC and matched histologically normal esophageal tissues,
      and examined IGF-IR expression levels in relation to clinicopathologic
      characteristics, body mass index (BMI), and the common IGF-IR polymorphism
      (G1013A), recently proposed to modify risk of obesity for EADC. Expression levels
      of IGF-IR mRNA were not significantly different between EADC and matched
      histologically normal esophageal epithelia. Although no significant associations
      were found between IGF-IR expression and BMI, tumor differentiation, stage or
      survival, when stratified by genotype, patients with the polymorphic A variant
      had significantly higher IGF-IR expression in EADC tissues compared with matched
      normal epithelia. These findings suggest that G1013A most likely modulates IGF-IR
      function, possibly by influencing gene transcription or mRNA stability, and
      represents a plausible mechanistic link underlying the association between
      obesity and esophageal malignancy.

PMID- 19582761
TI  - MSH6 G39E polymorphism and CpG island methylator phenotype in colon cancer.
AB  - The MSH6 G39E germline polymorphism is not associated with an increased risk of
      either microsatellite stable or unstable sporadic colorectal cancer. Other than
      microsatellite instability, however, most genetic and epigenetic changes of
      tumors associated with this common variant have not been studied. The objective
      of our investigation was to evaluate associations between the MSH6 G39E (116G>A)
      polymorphism and CpG island methylator phenotype (CIMP) and BRAF V600E mutations
      in tumors from a sample of 1048 individuals with colon cancer and 1964 controls
      from Utah, Northern California, and Minnesota. The G39E polymorphism (rs1042821)
      was determined by the five prime nuclease assay. CIMP was determined by
      methylation-specific polymerase chain reaction (PCR) of CpG islands in MLH1,
      methylated in tumors (MINT)1, MINT2, MINT31, and CDKN2A. The BRAF V600E mutation
      was determined by sequencing exon 15. In microsatellite stable tumors, homozygous
      carriers of the G39E polymorphism had an increased risk of CIMP+ colon cancer
      (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1, 4.2) and BRAF V600E
      mutation (OR 3.1, 95% CI 1.01, 9.7) in a case-control comparison. This finding
      was not observed in unstable tumors; however, power may have been low to detect
      an association. Age at diagnosis, family history, and alcohol use did not
      interact with MSH6 G39E and CIMP. The MSH6 G39E germline polymorphism may be
      associated with CIMP+ colon cancer.

PMID- 19582763
TI  - Parental expectations, experiences and reactions, sense of coherence and grade of
      anxiety related to routine ultrasound examination with normal findings during
      pregnancy.
AB  - OBJECTIVE: To investigate parents' expectations, experiences and reactions, sense
      of coherence and anxiety before and after a second-trimester routine ultrasound
      examination, with normal findings. METHODS: Before and after ultrasound
      questionnaires including the scales parents' expectations, experiences and
      reactions to routine ultrasound examination (PEER-U state of mind index), sense
      of coherence (SOC) and state and trait anxiety inventory (STAI), were sent to a 1
      year cohort of women and their partners. Replies received were 2183. RESULTS:
      Both parents had significantly less worried state of mind (PEER-U) after the
      examination than before. Women had a lower grade of state anxiety after than
      before, but for men there was no significant change. Before the ultrasound, women
      had a higher degree of worried state of mind, as well as a higher grade of state
      and trait anxiety and a lower sense of coherence, than men. The women showed a
      greater reduction in worried state of mind than the men after the ultrasound
      examination. There were no significant differences in sense of coherence before
      and after ultrasound. CONCLUSIONS: Women and men are affected in their
      psychological well-being in relation to a routine ultrasound examination, but
      their sense of coherence remains stable.

PMID- 19582764
TI  - Improved protocols for the illumina genome analyzer sequencing system.
AB  - In this unit, we describe a set of improvements we have made to the standard
      Illumina Genome Analyzer protocols to make the sequencing process more reliable
      in a high-throughput environment, reduce amplification bias, narrow the
      distribution of insert sizes, and reliably obtain high yields of data.

PMID- 19582765
TI  - Analysis of oxidative damage by gene-specific quantitative PCR.
AB  - This unit describes the gene-specific quantitative PCR-based (QPCR) assay, which
      is used to measure DNA integrity of both nuclear and mitochondrial genomes based
      on amplification of long DNA targets. QPCR can be used to quantify the formation
      of DNA damage and the kinetics of DNA repair by following restoration of
      amplification of the target DNA over time after removal of the damaging agent. A
      detailed protocol to set up QPCR in any laboratory, highlighting critical
      parameters for successful establishment of the assay and interpretation of the
      results, is provided here. Advantages (e.g., the use of nanogram amounts of DNA)
      and limitations (e.g., the inability to define the specific type of lesion
      present on the DNA) of using QPCR to assay DNA damage in human cells are also
      described.

PMID- 19582766
TI  - Bone marrow engraftment studies.
AB  - Bone marrow engraftment studies are used to evaluate the level of donor versus
      recipient cells in post-transplant peripheral blood or bone marrow specimens.
      Unique DNA fingerprints identified from the recipient and the donor are used to
      determine the proportion of each contained within the total DNA extracted from
      the post-transplant specimen. These percentages correspond to relative amounts of
      donor and recipient cells in the specimen. Engraftment studies are sequentially
      performed on transplant patients to monitor closely the levels of donor and
      recipient cells so that appropriate therapeutic intervention can proceed if and
      when needed. This unit describes the use of fluorescent PCR for amplification of
      genomic short tandem repeats (STR). STR analysis is now considered the gold
      standard for engraftment studies and provides a quick and accurate assessment of
      the contribution of both donor and/or recipient hematopoietic cells in post
      transplantation specimens.

PMID- 19582767
TI  - Internet resources in medical genetics.
AB  - This unit presents an overview of the most commonly used Web-based information
      resources for clinicians seeking to apply molecular or array-based genetic
      testing to patient care, obtain information on metabolic disease testing, learn
      more about newborn screening, or understand the molecular basis of inherited
      diseases, as well as for consumers seeking advocacy or scientific/management
      information, and also for genetics professional societies.

PMID- 19582769
TI  - Investigation of an epistastic effect between a set of TAAR6 and HSP-70 genes
      variations and major mood disorders.
AB  - Epistasis, the interaction between genes, is a topic of current interest in
      molecular and quantitative genetics. We have further studied a previously
      investigated sample of 187 major depressive disorder (MDD) patients, 171 bipolar
      disorder (BD) patients, and 288 controls, and tried to analyze the interaction
      between a set of variations of independent genes: the trace amine receptor 6
      (rs4305745, rs8192625, rs7452939, rs6903874, and rs6937506) and the heat shock
      protein 70 (rs562047, rs1061581, rs2227956). The multifactor dimensionality
      reduction (MDR) method was applied and the covariates associated with diagnosis
      were also controlled. A significant predictive value of specific interactions
      between genotypes located in the investigated genes was found. We then report
      preliminary evidence that the epistasis between trace amine receptor 6 and heat
      shock protein 70 variations may compose a risk profile for major mood disorders.
      The level of statistical significance (P < 0.001) and the testing balancing
      accuracy over 0.62 suggest a cautious optimism toward this result, although the
      possibility of false positivity warrants further analyses in independent samples.

PMID- 19582771
TI  - Improving SNR of RF coils using composite coil elements.
AB  - A composite coil element consists of up to three independent orthogonal loops. It
      improves the flexibility in shaping the radio frequency (RF) field in its
      vicinity, compared with a single-loop coil element. Computer simulations were
      conducted to explore the potential advantages of this type of coil configuration
      for improving the signal-to- noise ratio (SNR), including the intrinsic SNR
      (ISNR) and the realistic SNR, when the effects of resistive loss of the coil were
      included. A 'half-space' model was considered, with a variable B(0) direction
      relative to the surface of a large conductive medium. The SNR performance of a
      square single-loop coil parallel to the surface of the medium was compared with
      that of a composite coil element where up to two additional orthogonal square
      loops of the same size were added to the single coil loop. The SNR performances
      of coil arrays consisting of single-loop elements and composite elements were
      also evaluated. The RF field was calculated using the finite-difference time
      domain method. The results show that the composite coil element has a
      substantially better ISNR at all depths from the surface than that of a single
      loop element covering the same surface area. Furthermore, the ISNR of a composite
      element is not sensitive to the surface orientation relative to the B(0) field.
      The computer simulation also revealed that at 128 MHz, the resistive loss from
      the copper coil loops standing upright on the surface at room temperature is
      substantial compared to the loss in the medium. Consequently, the realistic SNR
      is significantly lower than ISNR at 128 MHz for a composite coil element. The
      coil loading by the medium becomes more dominant at 170 and 298 MHz, and the
      differences between the realistic SNR and ISNR become smaller at these higher
      frequencies.

PMID- 19582768
TI  - Preliminary evidence of ubiquitin proteasome system dysregulation in
      schizophrenia and bipolar disorder: convergent pathway analysis findings from two
      independent samples.
AB  - Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many
      genes contributing to their etiologies. The aim of this investigation was to
      search for dysregulated molecular and cellular pathways for these disorders as
      well as psychosis. We conducted a blood-based microarray investigation in two
      independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control =
      8) and Taiwan (SCZ = 11, BPD = 14, control = 16). Diagnostic groups were compared
      to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n =
      6), Taiwan (n = 14)] were compared to subjects without such history [PSYCH(-):
      San Diego (n = 11), Taiwan (n = 14)]. Analyses of covariance comparing mean
      expression levels on a gene-by-gene basis were conducted to generate the top 100
      significantly dysregulated gene lists for both samples by each diagnostic group.
      Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results
      showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical
      pathways for BPD and psychosis diagnostic groups across both samples with a
      considerably low likelihood of a chance occurrence (P = 0.001). No overlap in
      dysregulated genes populating these pathways was observed between the two
      independent samples. Findings provide preliminary evidence of UPS dysregulation
      in BPD and psychosis as well as support further investigation of the UPS and
      other molecular and cellular pathways for potential biomarkers for SCZ, BPD,
      and/or psychosis.

PMID- 19582773
TI  - Shortening of human cell life span by induction of p16ink4a through the platelet
      derived growth factor receptor beta.
AB  - Mesenchymal stem cells (MSCs) are attracting a great deal of attention because
      they represent a valuable source of cells for use in regenerative medicine. In
      human cell culture it is important to obtain large numbers of cells for use in
      therapy. In this study, we attempted to prolong life span of a marrow-derived
      mesenchymal stem cell using a combination of growth factors and hormones.
      Furthermore we tested whether chemically defined culture conditions are
      sufficient for maintenance of multipotent mesenchymal stem cells. Epidermal
      growth factor, platelet-derived growth factor-BB (PDGF-BB), acidic fibroblast
      growth factor (FGF), basic FGF, and leukemia inhibitory factor were found to be
      key factors for the mesenchymal stem cell proliferation. The combination of these
      growth factors showed extremely strong mitogenic activity, and simultaneously
      induced the expression of cyclin-dependent kinase inhibitor p16ink4a protein and
      premature senescence more rapidly than serum-supported culture conditions. The
      induction of p16ink4a by growth factors was mediated through the mitogen
      activated protein kinase (MAPK) cascade. Excess growth stimulation by growth
      factors was thus one of the culture stress signals and a trigger of premature
      senescence at least in human cells.

PMID- 19582774
TI  - Protein cytoskeleton and overexpression of Na(+),K(+)-ATPase in opossum kidney
      cells.
AB  - Previous studies have shown that over time in culture opossum kidney (OK) cells
      are endowed with increased Na(+),K(+)-ATPase activity and expression (Silva et
      al., 2006, J Membr Biol 212:163-175; Silva and Soares-da-Silva, 2007, Am J
      Physiol Regul Integr Comp Physiol 293:R1764-R1770). The present work evaluated
      the cytoskeleton reorganization in OK cells at passages 40 and 80 in culture and
      its possible relationship with membrane transport proteins and cell morphology.
      It is shown that OK cells with 80 passages in culture have increased size,
      internal complexity, and total protein expression. In OK cells with 80 passages
      in culture the use of in-cell western showed that ezrin/radixin/moesin complex
      was increased by 20%. The most abundant ankyrin-G isoform in OK cells with 40
      passages was the approximately 200/220 kDa isoform, whereas in OK cells with 80
      passages the most abundant isoform was the approximately 170 kDa isoform. The
      spectrin-betaII approximately 240 kDa isoform, the predominant isoform in OK
      cells with 40 passages, was marginally detected in OK cells with 80 passages.
      Besides Na(+),K(+)-ATPase, GLUT2, and NHE3 expression was also significantly
      increased in OK cells with 80 passages. It is concluded that the prolonged cell
      passaging of OK cells results in an interesting and valuable experimental model
      to analyze the reorganization of the renal cell cytoskeleton proteins and its
      relationship with transporter and signaling membrane proteins.

PMID- 19582775
TI  - Role of Smad3, acting independently of transforming growth factor-beta, in the
      early induction of Wnt-beta-catenin signaling by parathyroid hormone in mouse
      osteoblastic cells.
AB  - Parathyroid hormone (PTH) exerts an anabolic action on bone but the mechanisms
      are incompletely understood. We showed previously that PTH interacts with the
      canonical Wnt-beta-catenin signaling pathway via the transforming growth factor
      (TGF)-beta signaling molecule, Smad3, to modulate osteoblast differentiation and
      apoptosis. Here, we examined which actions of Smad3 are TGF-beta-independent in
      stimulating the osteoblast phenotype and PTH-induced Wnt-beta-catenin signaling.
      For this, the TGF-beta receptor type 1 [activin receptor-like kinase (ALK5)]
      inhibitor (SB431542), and a Smad3 mutant in which the site normally
      phosphorylated by ALK5 is mutated from SSVS to AAVA, was used. PTH induced total
      beta-catenin and reduced phosphorylated beta-catenin levels at 1, 6, and 24 h in
      mouse osteoblastic MC3T3-E1 cells. Transient transfection of Smad3AAVA inhibited
      the PTH induction of total beta-catenin and reduction of phosphorylated beta
      catenin levels at 6 and 24 h, but not at 1 h, indicating that the early effects
      occur independently of TGF-beta receptor signaling. On the other hand, MC3T3-E1
      cell clones in which Smad3AAVA was stably expressed demonstrated elevated beta
      catenin levels, although alkaline phosphatase (ALP) activity and mineralization
      were unaltered. In contrast, MC3T3-E1 cell clones in which wild-type Smad3 was
      stably expressed exhibited increased ALP activity and mineralization that were
      decreased by the ALK5 inhibitor, SB431542, although the beta-catenin levels
      induced in these cells were not modulated. In conclusion, the present study
      indicates that PTH induces osteoblast beta-catenin levels via Smad3 independently
      of, and dependently on, TGF-beta in the early and later induction phases,
      respectively.

PMID- 19582776
TI  - Are abnormal premorbid personality traits associated with Alzheimer's disease? -
      A case-control study.
AB  - OBJECTIVE: To examine the association between premorbid personality traits,
      social networks and AD, using a case-control design, and two informant-based
      retrospective assessments of premorbid personality. METHODS: Cases consisted of
      217 Subjects diagnosed with probable late onset Alzheimer's disease (160 females
      and 57 males). Recruitment was from both community and nursing home settings.
      Controls consisted of 76 unaffected siblings (44 females and 32 males) of
      patients with AD. Both cases and controls received informant ratings of premorbid
      personality. RESULTS: A selection of abnormal personality traits were over
      represented in the AD group. AD was particularly associated with Cluster A
      personality disorder traits (Paranoid, Schizoid, Schizotypal). AD cases had
      correspondingly sparser social networks. CONCLUSIONS: There is an association
      between abnormal personality traits and AD. Individuals with AD also appear to
      have had lower levels of social interactivity.

PMID- 19582777
TI  - The relative role of drift and selection in shaping the human skull.
AB  - Human populations across the world vary greatly in cranial morphology. It is
      highly debated to what extent this variability has accumulated through neutral
      processes (genetic drift) or through natural selection driven by climate. By
      taking advantage of recent work showing that geographic distance along landmasses
      is an excellent proxy for neutral genetic differentiation, we quantify the
      relative role of drift versus selection in an exceptionally large dataset of
      human skulls. We show that neutral processes have been much more important than
      climate in shaping the human cranium. We further demonstrate that a large
      proportion of the signal for natural selection comes from populations from
      extremely cold regions. More generally, we show that, if drift is not explicitly
      accounted for, the effect of natural selection can be greatly overestimated.

PMID- 19582778
TI  - Visualizing disease associations: graphic analysis of frequency distributions as
      a function of age using moving average plots (MAP) with application to
      Alzheimer's and Parkinson's disease.
AB  - Age-related variation in marker frequency can be a confounder in association
      studies, leading to both false-positive and false-negative findings and
      subsequently to inconsistent reproducibility. We have developed a simple method,
      based on a novel extension of moving average plots (MAP), which allows
      investigators to inspect the frequency data for hidden age-related variations.
      MAP uses the standard case-control association data and generates a birds-eye
      view of the frequency distributions across the age spectrum; a picture in which
      one can see if, how, and when the marker frequencies in cases differ from that in
      controls. The marker can be specified as an allele, genotype, haplotype, or
      environmental factor; and age can be age-at-onset, age when subject was last
      known to be unaffected, or duration of exposure. Signature patterns that emerge
      can help distinguish true disease associations from spurious associations due to
      age effects, age-varying associations from associations that are uniform across
      all ages, and associations with risk from associations with age-at-onset. Utility
      of MAP is illustrated by application to genetic and epidemiological association
      data for Alzheimer's and Parkinson's disease. MAP is intended as a descriptive
      method, to complement standard statistical techniques. Although originally
      developed for age patterns, MAP is equally useful for visualizing any
      quantitative trait.

PMID- 19582779
TI  - Characterization of the expression of variant and standard CD44 in prostate
      cancer cells: identification of the possible molecular mechanism of CD44/MMP9
      complex formation on the cell surface.
AB  - CD44 is a glycosylated adhesion molecule and osteopontin is one of its ligand.
      CD44 undergoes alternative splicing to produce variant isoforms. Our recent
      studies have shown an increase in the surface expression of CD44 isoforms (sCD44
      and v4-v10 variant CD44) in prostate cancer cells over-expressing osteopontin
      (PC3/OPN). Formation of CD44/MMP9 complex on the cell surface is indispensable
      for MMP9 activity. In this study, we have characterized the expression of variant
      CD44 using RT-PCR, surface labeling with NHS-biotin, and immunoblotting.
      Expression of variant CD44 encompassing v4-v10 and sCD44 at mRNA and protein
      levels are of the same levels in PC3 and PC3/OPN cells. However, an increase in
      the surface expression of v6, v10, and sCD44 in PC3/OPN cells suggest that OPN
      may be a ligand for these isoforms. We then proceeded to determine the role of
      sCD44 in MMP9 activation. Based on our previous studies in osteoclasts, we
      hypothesized that phosphorylation of CD44 has a role on its surface expression
      and subsequent activation of MMP9. We have prepared TAT-fused CD44 peptides
      comprising unphosphorylated and constitutively phosphorylated serine residues at
      positions Ser323 and Ser325. Transduction of phosphopeptides at Ser323 and
      Ser323/325 into PC3 cells reduced the surface levels of CD44, MMP9 activity, and
      cell migration; but had no effect on the membrane localization of MMP9. However,
      MMP9 knock-down PC3 cells showed reduced CD44 at cellular and surface levels.
      Thus we conclude that surface expression of CD44 and activation of MMP9 on the
      cell surface are interdependent.

PMID- 19582781
TI  - C957T polymorphism of dopamine D2 receptor gene affects striatal DRD2 in vivo
      availability by changing the receptor affinity.
AB  - The C957T polymorphism of the human dopamine D2 receptor gene (DRD2) regulates
      DRD2 availability in striatum in vivo. Specifically, the T allele predicts high
      DRD2 availability in healthy volunteers (T/T>T/C>C/C). However, this finding was
      unexpected as in vitro the T allele is associated with a decrease in DRD2 mRNA
      stability and synthesis of the receptor through a putative alteration in the
      receptor mRNA folding. To elucidate further how changes in DRD2 density (B(max))
      and affinity (K(D)) contribute to the differences in DRD2 availability between
      the C957T genotypes, we studied these parameters separately in a sample of 45
      healthy volunteers. The subjects had two PET scans with [(11)C]raclopride (high
      and low specific radioactivity scans) for the estimation of B(max) and K(D), and
      were genotyped for the C957T. Moreover, the role of the related and previously
      studied functional TaqIA polymorphism of ankyrin repeat and kinase domain
      containing 1 (ANKK1) gene was reassessed for comparative purposes. The results
      indicate that the C957T increased binding potential by decreasing DRD2 K(D)
      (C/C>C/T>T/T), while B(max) was not significantly altered. These preliminary
      findings indicate that the C957T genotype-dependent changes in DRD2 availability
      are driven by alterations in receptor affinity and putatively in striatal
      dopamine levels. This mechanism seems to differ from that observed previously for
      the ANKK1 gene TaqIA polymorphism, where the minor allele (A1) affects DRD2
      availability predominantly by changing B(max). The hypothesis that the two SNPs
      may have independent effects on dopamine neurotransmission needs to be further
      tested.

PMID- 19582782
TI  - Differential effects of topiramate on prefrontal glutamatergic transmission when
      combined with raclopride or clozapine.
AB  - Treatment with topiramate may improve negative symptoms in schizophrenia when
      added to typical antipsychotic drugs (APDs) but not to clozapine. Both
      dopaminergic and glutamatergic transmissions in the medial prefrontal cortex
      (mPFC) are facilitated by atypical, but not typical, APDs, which is thought to
      improve negative symptoms and cognitive dysfunction in schizophrenia. Our
      previous results show that topiramate increases prefrontal dopamine (DA) outflow
      when added to the D(2/3) receptorantagonist raclopride. Here, using intracellular
      recording in vitro, we investigated the effects of topiramate on glutamatergic
      neurotransmission in the rat mPFC, both when given alone and in combination with
      raclopride or clozapine. Neither topiramate nor raclopride alone had any effect
      on N-methyl-D-aspartate (NMDA)-induced currents in pyramidal cells of the mPFC.
      However, the combination of topiramate and raclopride facilitated the NMDA
      induced currents, and this effect was blocked by the D1 receptor antagonist
      SCH23390. Topiramate also facilitated the effect of a submaximal, but inhibited
      the effect of a maximal, concentration of clozapine on these currents. The effect
      of combined topiramate and a submaximal concentration of clozapine could be
      blocked by SCH23390. In addition, combined topiramate and raclopride facilitated
      excitatory postsynaptic potentials. In contrast, topiramate inhibited clozapine's
      facilitating effect on these potentials. These data may help explain the
      improvement of negative symptoms when topiramate is used as adjunctive therapy in
      schizophrenic patients receiving typical APDs, but they may also shed light on
      the observed deterioration of symptoms when topiramate is added to full dose
      clozapine.

PMID- 19582783
TI  - Amphetamine and environmentally induced hyperthermia differentially alter the
      expression of genes regulating vascular tone and angiogenesis in the meninges and
      associated vasculature.
AB  - An amphetamine (AMPH) regimen that does not produce a prominent blood-brain
      barrier breakdown was shown to significantly alter the expression of genes
      regulating vascular tone, immune function, and angiogenesis in vasculature
      associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague
      Dawley rats were given either saline injections during environmentally-induced
      hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10,
      and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed
      either 3 h or 1 day after dosing, and total RNA and protein was isolated from the
      meninges, arachnoid and pia membranes, and associated vasculature (MAV) that
      surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular
      tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating
      that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH,
      and EIH to a lesser extent, elicited a significant inflammatory response at 3 h
      as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1,
      and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular
      homeostasis such as Icam1 and Hsp72 were also observed. The increased expression
      of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek
      (genes involved in stimulating angiogenesis) from AMPH exposure suggest that
      angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH
      compared to EIH. Alterations in vascular-related gene expression in the parietal
      cortex and striatum after AMPH were less in magnitude than in MAV, indicating
      less of a disruption of vascular homeostasis in these two regions. Changes in the
      levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV,
      compared to those in striatum and parietal cortex, imply an interaction between
      these regions to regulate the levels of insulin-like growth factor after AMPH
      damage. Thus, the vasculature and meninges surrounding the surface of the
      forebrain may be an important region in which AMPHs can disrupt vascular
      homeostasis.

PMID- 19582784
TI  - Ultrastructural analysis of local collaterals of rat ventral tegmental area
      neurons: GABA phenotype and synapses onto dopamine and GABA cells.
AB  - Local synapses formed by nondopamine cells within the ventral tegmental area
      (VTA) are thought to provide an important regulatory influence on the activity
      patterns of dopamine (DA) neurons. However, ultrastructural confirmation of intra
      areal synapses formed by VTA neurons is lacking, and the synaptic targets of
      these connections have not been examined. We performed discrete injections of the
      specific anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL) and used
      electron microscopy to visualize immunoperoxidase labeling within the local
      collaterals of VTA cells. The phenotype of target neurons was determined by
      immunogold-silver labeling for GABA or for tyrosine hydroxylase within DA
      neurons. Within or immediately adjacent to the VTA injection sites, PHAL was
      incorporated into the soma and dendrites of both GABA and DA cells. Tracer was
      also detected within myelinated and unmyelinated axons as well as axon terminals.
      Some labeled terminals formed identifiable synapses, the majority of which (78%)
      had symmetric morphology (presumably inhibitory). Both DA and GABA dendrites were
      contacted by these intrinsic axons. Postembedding immunogold labeling verified
      that local axon collaterals arose mainly from GABA cells (DA neurons are not
      known to issue recurrent collaterals). Nevertheless, a few synapses with
      asymmetric morphology (presumably excitatory) were also noted; whether these
      derive from local glutamate neurons requires further investigation. Hence, our
      data provide ultrastructural support for the long standing assumption that GABA
      VTA neurons synapse locally onto DA cells. The findings also suggest the presence
      of disinhibitory and possibly excitatory circuitry intrinsic to the VTA.

PMID- 19582785
TI  - Methods for detecting interactions between genetic polymorphisms and prenatal
      environment exposure with a mother-child design.
AB  - Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal
      environmental exposures are of particular concern because of the heightened
      susceptibility of the fetus and infant to diverse environmental pollutants.
      Marked inter-individual variation in response to the same level of exposure was
      observed in both mothers and their newborns, indicating that susceptibility might
      be due to genetic factors. With the mother-child pair design, existing methods
      developed for parent-child trio data or random sample data are either not
      applicable or not designed to optimally use the information. To take full
      advantage of this unique design, which provides partial information on genetic
      transmission and has both maternal and newborn outcome status collected, we
      developed a likelihood-based method that uses both the maternal and the newborn
      information together and jointly models gene-environment interactions on maternal
      and newborn outcomes. Through intensive simulation studies, the proposed method
      has demonstrated much improved power in detecting gene-environment interactions.
      The application on a real mother-child pair data from a study conducted in
      Krakow, Poland, suggested four significant gene-environment interactions after
      multiple comparisons adjustment.

PMID- 19582786
TI  - Assessment of SNP streak statistics using gene drop simulation with linkage
      disequilibrium.
AB  - We describe methods and programs for simulating the genotypes of individuals in a
      pedigree at large numbers of linked loci when the alleles of the founders are
      under linkage disequilibrium. Both simulation and estimation of linkage
      disequilibrium models are shown to be feasible on a genome wide scale. The
      methods are applied to evaluate the statistical significance of streaks of loci
      at which sets of related individuals share a common allele. The effects of
      properly allowing for linkage disequilibrium are shown to be important as they
      explain many of the large observations. This is illustrated by reanalysis of a
      previously reported linkage of prostate cancer to chromosome 1p23.

PMID- 19582787
TI  - Transforming growth factor-beta1 regulation of ATF-3 and identification of ATF-3
      target genes in breast cancer cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a crucial molecule for
      stimulation of breast cancer invasion and formation of bone metastases. The
      molecular mechanisms of how TGF-beta1 mediates these effects have yet to be
      completely determined. We have found that activating transcription factor-3 (ATF
      3) is strongly stimulated and its level is sustained by TGF-beta1 in highly
      invasive and metastatic human breast cancer (MDA-MB231) and in mouse mammary pad
      tumor cells (r3T). ATF-3 is also overexpressed in human primary breast cancer
      tissue. Overexpression of ATF-3 increased normal human mammary epithelial cell
      number and DNA synthesis suggesting a role for ATF-3 in cell proliferation. The
      functional role of ATF-3 in breast cancer progression was determined by the RNA
      interference technique. Knockdown of ATF-3 by ATF-3 shRNA in MDA-MB231 cells
      decreased expression of cell cycle gene, cyclin A1 in MDA-MB231 cells. ATF-3
      shRNA also decreased expression of an invasive and metastatic gene, matrix
      metalloproteinase-13 (MMP-13; collagenase-3) in these cells. Chromatin
      immunoprecipitation experiments identified the direct physical interaction of ATF
      3 protein on the human MMP-13 promoter. Thus, the dysregulation of ATF-3 by TGF
      beta1 is likely to activate cyclin A1 and MMP-13 genes in breast cancer cells and
      that would be key to the subsequent cancer cell invasion and metastasis.

PMID- 19582789
TI  - Surgeons and scientists: working together in embryo research.
AB  - Most surgeons in academic hospitals will have had a request from an enthusiastic
      research scientist to take samples of tissue during an operation. It seems
      reasonable and most patients will respond positively. But of course it is not
      quite that simple. The regulation of donation of human tissue for basic research
      is clearly defined but usually less rigorous than that which covers translational
      research and clinical trials. An exception has been the donation of embryos for
      embryonic stem cell derivation. The specific issues related to obtaining cells
      from patients for this work has resulted in a different relationship between
      scientist and clinician. This will be considered.

PMID- 19582788
TI  - Prostaglandin E2 inhibits the proliferation of human gingival fibroblasts via the
      EP2 receptor and Epac.
AB  - Elevated levels of prostaglandins such as PGE(2) in inflamed gingiva play a
      significant role in the tissue destruction caused by periodontitis, partly by
      targeting local fibroblasts. Only very few studies have shown that PGE(2)
      inhibits the proliferation of a gingival fibroblast (GF) cell line, and we
      expanded this research by using primary human GFs (hGFs) and looking into the
      mechanisms of the PGE(2) effect. GFs derived from healthy human gingiva were
      treated with PGE(2) and proliferation was assessed by measuring cell number and
      DNA synthesis and potential signaling pathways were investigated using selective
      activators or inhibitors. PGE(2) inhibited the proliferation of hGFs dose
      dependently. The effect was mimicked by forskolin (adenylate cyclase stimulator)
      and augmented by IBMX (a cAMP-breakdown inhibitor), pointing to involvement of
      cAMP. Indeed, PGE(2) and forskolin induced cAMP generation in these cells. Using
      selective EP receptor agonists we found that the anti-proliferative effect of
      PGE(2) is mediated via the EP(2) receptor (which is coupled to adenylate cyclase
      activation). We also found that the effect of PGE(2) involved activation of Epac
      (exchange protein directly activated by cAMP), an intracellular cAMP sensor, and
      not PKA. While serum increased the amount of phospho-ERK in hGFs by approximately
      300%, PGE(2) decreased it by approximately 50%. Finally, the PGE(2) effect does
      not require endogenous production of prostaglandins since it was not abrogated by
      two COX-inhibitors. In conclusion, in human gingival fibroblasts PGE(2) activates
      the EP(2)-cAMP-Epac pathway, reducing ERK phosphorylation and inhibiting
      proliferation. This effect could hamper periodontal healing and provide further
      insights into the pathogenesis of inflammatory periodontal disease.

PMID- 19582790
TI  - SRrp37, a novel splicing regulator located in the nuclear speckles and nucleoli,
      interacts with SC35 and modulates alternative pre-mRNA splicing in vivo.
AB  - We report here the identification and characterization of a novel SR-related
      protein, referred to as SRrp37, based on its apparent molecular weight and
      subcellular location. SRrp37 was identified through a yeast two-hybrid screen
      during the course of searching for proteins interacting with pNO40, a ribosomal
      60S core subunit. SRrp37 exhibited two alternative spliced isoforms generated by
      differential usage of the translation start site with the longer one, SRrp37,
      initiating at first exon and the shorter, SRrp37-2, starting from exon 2. Three
      distinct motifs can be discerned in the SRrp37 protein: (1) a serine-arginine
      (SR) dipeptide enriched domain, (2) a polyserine stretch, and (3) a potential
      nucleolar localization signal comprising a long array of basic amino acids.
      SRrp37's message was translated in tissue-specific patterns with both isoforms
      expressed at comparable levels in tissues showing expression. Indirect
      immunofluorescence analysis with an anti-SRrp37 antibody, as well as an
      experiment using myc-tagged proteins, demonstrated that SRrp37 was localized in
      nucleoli and nuclear speckles. GST pull-down assay showed that SRrp37 interacted
      physically with SC35. Using adenovirus E1A and chimeric calcitonin/dhfr
      constructs as splicing reporter minigenes, we found that SRrp37 modulated
      alternative 5' and 3' splicing in vivo. Together, SRrp37 may participate directly
      in splicing regulation or indirectly through interaction with SC35. Studies on
      this novel splicing regulator may provide new information on the intricate
      splicing machinery as related to the RNA metabolism involving processing of mRNA
      and rRNA.

PMID- 19582791
TI  - The ontogeny of exploratory behavior in male and female adolescent rats (Rattus
      norvegicus).
AB  - During adolescence, rats gain independence from their mothers and disperse from
      the natal burrow, with males typically dispersing further than females. We
      predicted that, if dispersal patterns are associated with responsiveness to
      novelty, exploratory behavior in novel environments would increase across
      adolescence, and males would explore more than females. Alternatively, females
      might explore more than males, if females are more motivated than males to learn
      about the immediate environment or if females have poorer spatial abilities than
      males. Twenty-five male and 21 female rats were exposed to two novel environments
      (open field and elevated plus-maze) during early, mid-, or late adolescence.
      Total locomotion and amount of exploration directed towards aversive areas
      increased across adolescence, even when body weight was included as a covariate.
      Female adolescents locomoted more and spent more time exploring aversive areas
      than males. Developmental changes in neural function potentially underlie age and
      sex differences in exploratory behavior.

PMID- 19582792
TI  - Genetic and gene-environment interaction effects on preschoolers' social
      behaviors.
AB  - This study examined effects from a specific dopamine receptor gene (DRD4),
      environmental influences from parents and peers, and the interaction between
      them, on aggressive and prosocial behaviors of preschoolers. Children were
      classified as DRD4-L (n = 27) if they had at least one DRD4 allele with six to
      eight repeats and as DRD4-S (n = 35) if not. Parent-child interactions were coded
      when children were 3-4 years old. Peer interaction data and parent questionnaires
      were collected at age 5. DRD4-L children shared less with each other and parents
      were less sensitive during parent-twin triadic interactions. Also, genotype
      interacted with peer aggression to affect children's aggression during a peer
      play interaction at age 5, and genotype interacted with prior parental
      sensitivity to affect later externalizing problems. Thus, children having a
      certain genetic disposition may be more sensitive to certain environmental
      stimuli and therefore more likely to exhibit aggressive behaviors under more
      stressful circumstances.

PMID- 19582794
TI  - Development of dynamic stability in children's rhythmic movement.
AB  - This study examined the hypothesis that the stability of rhythmic motor patterns
      increases with developmental age in children. Children aged 6 and 10 years and
      adults (18- to 23-year-olds) rocked back and forth at their preferred amplitude
      and frequency while seated on a wooden box placed atop a force platform.
      Participants performed the seated rocking task with their feet supported and
      unsupported. There was an age-related decrease in rocking frequency and
      variability of the rocking cycle period, while the stability of the rocking
      dynamics increased, as indexed by the standard deviation of the phase angle of
      center of pressure motion. The presence of foot support decreased the stability
      of the rocking dynamics and reduced cycle period variability in the children, but
      not the adults. The results revealed that increments of age are associated with
      an increase in the stability of rhythmic motor patterns even when environmental
      conditions are altered.

PMID- 19582793
TI  - Olfactory learning in the rat immediately after birth: Unique salience of first
      odors.
AB  - An infant rat's chance of survival is increased when it remains close to the
      nest. Early olfactory learning supports such adaptive behavior. Previous
      experiments indicated that non-associative odor exposure immediately after birth
      promoted later attachment to a similarly scented artificial nipple. The goal of
      the current experiments was to extend these findings on olfactory learning in the
      hours after birth by: exposing pups to more than one odor exposure (Experiment
      1), dissecting the role of timing versus order of odor exposure (Experiment 2),
      testing the odor specificity of these effects (Experiments 3 and 4), and
      evaluating associative odor conditioning soon after birth (Experiment 5). Without
      explicit prior odor experience, pups only hours old do not respond much to a
      novel odor. Prior non-associative odor experience increases later motor activity
      to that same odor and to novel odors. Furthermore, these findings may be specific
      to certain amodal dimensions of the (in our case) lemon odor exposure. Single
      odor non-associative and associative conditioning was equally effective
      immediately after birth and during the third postnatal hour. Nevertheless, pups
      given two mere odor exposures responded to the first one more than the second at
      test, regardless of whether the exposures began immediately or 2 hr after birth.
      Possible mechanisms for these findings concerning early olfactory learning are
      discussed.

PMID- 19582795
TI  - Prognostic role of myeloid cell leukemia-1 protein (Mcl-1) expression in human
      gastric cancer.
AB  - BACKGROUND: Myeloid cell leukemia-1 protein (Mcl-1), an anti-apoptotic member of
      Bcl-2 family, has been reported to be correlated with tumor progression. The
      purpose of this study was to establish the prognostic value of Mcl-1 expression
      in human gastric cancer. METHODS: Western blot assay was performed to detect the
      expression of Mcl-1 protein in human gastric cancer cell lines and tissues, while
      Mcl-1 expression in resected gastric cancer tissue samples was analysed by
      immunohistochemistry. RESULTS: The level of Mcl-1 protein expression in gastric
      cancer cell lines was significantly higher than that in gastric mucosa epithelial
      cell line. Moreover, the expression level of Mcl-1 protein was significantly
      higher in gastric cancer tissues than corresponding noncancerous tissues.
      Expression was correlated with T classification (P = 0.003), metastasis (P =
      0.001), clinical stage (P = 0.010), and venous invasion (P = 0.004). Patients
      with high Mcl-1 expression showed poorer 5-year overall survival than patients
      with low Mcl-1 expression (P = 0.012; log-rank test). Further univariate and
      multivariate analysis suggested that high Mcl-1 expression was an independent
      prognostic marker for the disease. CONCLUSION: Mcl-1 is highly upregulated in
      gastric cancer and high Mcl-1 expression is correlated with a poor prognosis in
      gastric cancer patients. Thus, Mcl-1 can be utilized as an independent prognostic
      factor.

PMID- 19582796
TI  - Total scapulectomy and constrained reverse total shoulder reconstruction for a
      Ewing's sarcoma.
AB  - BACKGROUND: Total scapulectomy and intra-articular resection of the glenohumeral
      joint indicates the Malawer Type III shoulder girdle resection. MATERIALS AND
      METHODS: The modified Tikhoff-Linberg total scapulectomy and constrained reverse
      total shoulder reconstruction for a Ewing's sarcoma of the scapula is presented.
      A combined approach has been used. The deltoid, trapezius, rhomboids, levator
      scapulae, latissimus dorsi, and serratus anterior were preserved. the tumor was
      removed en bloc by disarticulation of the acromioclavicular and the glenohumeral
      joints. The scapular prosthesis was suspended by the muscles. A constrained
      reverse humeral prosthesis was implanted after osteotomy of the humeral head.
      RESULTS: There were no intraoperative or postoperative complications; surgical
      margins were clear. At 12 months postoperatively, the patient has a stable and
      painless shoulder. CONCLUSION: The goal of shoulder reconstructions is to provide
      a stable and painless joint that allows positioning of the arm and hand in space.
      Compared to those patients left without a scapula reconstruction, prosthetic
      replacement of the scapula and shoulder partially restores abduction and external
      rotation and improves cosmesis.

PMID- 19582797
TI  - Structural modeling and biochemical studies reveal insights into the molecular
      basis of the recognition of beta-2-microglobulin by antibody BBM.1.
AB  - Human beta-2-microglobulin (beta2m) is the light chain of human leucocyte antigen
      I (HLA-I). It can disassociate from HLA-I and accumulate to cause serious
      dialysis-related amyloidosis (DRA) in long-term hemodialysis patients. Monoclonal
      antibody (mAb) BBM.1 can recognize both free-form and HLA-I associated beta2m. It
      can be used for specific elimination of beta2m from serum and can induce
      apoptosis of several types of tumor cells, and thus has great therapeutic
      potential. In this study, we constructed structural models of the BBM.1 Fv
      (fragment of the variable domain) and the BBM.1 Fv-beta2m complex, followed by
      biochemical evaluation. Analysis of the optimal complex model reveals that the
      previously identified immunodominant residues Glu(44) and Arg(45) of beta2m have
      direct interactions with BBM.1, while Asp(38) exerts its function mainly via
      stabilization of Arg(45). In addition, Arg(81) of beta2m is a newly identified
      immunodominant residue to have direct interaction with BBM.1. Further modeling
      study shows no steric conflict between the antibody and the HLA-I heavy chain.
      These results provide insights into the molecular basis of the recognition of
      beta2m by BBM.1 and explain why BBM.1 can bind both free-form and HLA-1
      associated beta2m. This information could be exploited in the engineering and
      improvement of BBM.1 and the development of other beta2m-targeting mAbs for
      therapeutic purposes.

PMID- 19582798
TI  - Needs assessment of family caregivers of cancer survivors: three cohorts
      comparison.
AB  - PURPOSE/BACKGROUND: Caregivers' quality of life (QOL) may be maximized when the
      caregivers' needs in the context of cancer care are met. Therefore, determining
      what needs are not being satisfied for family caregivers should be the first step
      in the development of programs designed to enhance caregivers' QOL. METHOD: The
      28-item Needs Assessment of Family Caregivers-Cancer (NAFC-C) scale was developed
      and validated with caregivers at three different survivorship phases: at 2 months
      (n=162), 2 years (n=896), and 5 years (n=608) post-diagnosis. RESULTS: The NAFC-C
      helped to identify caregivers whose needs were less likely to be met, based on
      their age and ethnicity. Furthermore, the extent to which caregivers'
      psychosocial needs were not being met was a consistent and strong predictor of
      poor mental health across all phases of survivorship, beyond the effects of a
      host of demographic characteristics. CONCLUSION: Findings suggest that
      interventions designed to help caregivers manage their own emotional distress as
      well as the survivors' distress, find meaning in the cancer caregiving
      experience, and foster supportive familial relationship will benefit caregivers
      by improving their QOL, not only during the time of diagnosis and treatment but
      years after.

PMID- 19582799
TI  - Balancing the funds in the New Cooperative Medical Scheme in rural China:
      determinants and influencing factors in two provinces.
AB  - In recent years, the central government in China has been leading the re
      establishment of its rural health insurance system, but local government
      institutions have considerable flexibility in the specific design and management
      of schemes. Maintaining a reasonable balance of funds is critical to ensure that
      the schemes are sustainable and effective in offering financial protection to
      members. This paper explores the financial management of the NCMS in China
      through a case study of the balance of funds and the factors influencing this, in
      six counties in two Chinese provinces. The main data source is NCMS management
      data from each county from 2003 to 2005, supplemented by: a household
      questionnaire survey, qualitative interviews and focus group discussions with all
      local stakeholders and policy document analysis. The study found that five out of
      six counties held a large fund surplus, whilst enrolees obtained only partial
      financial protection. However, in one county greater risk pooling for enrolees
      was accompanied by relatively high utilisation levels, resulting in a fund
      deficit. The opportunities to sustainably increase the financial protection
      offered to NCMS enrolees are limited by the financial pressures on local
      government, specific political incentives and low technical capacities at the
      county level and below. Our analysis suggests that in the short term, efforts
      should be made to improve the management of the current NCMS design, which should
      be supported through capacity building for NCMS offices. However, further medium
      term initiatives may be required including changes to the design of the schemes.

PMID- 19582801
TI  - Comparison of fundal height measurement and sonographically measured fetal
      abdominal circumference in the prediction of high and low birth weight at term.
AB  - OBJECTIVES: To compare the diagnostic value of fundal height and sonographically
      measured fetal abdominal circumference in the prediction of high and low birth
      weight in routine practice between 37 and 41 weeks' gestation. METHODS: Data were
      obtained from a multicenter study of 19 415 women in France and Belgium. In this
      study we included 7138 low-risk women from that population who underwent fundal
      height measurements no more than 8 days before delivery (Population A). We also
      included another 1689 women with both fundal height measurements and fetal
      ultrasound measurements obtained no more than 8 days before delivery (Population
      B). Population A was used to calculate the parameters of equations for estimating
      fetal weight according to fundal height alone (EFW(FH)) or fundal height in
      combination with other clinical indicators (EFW(FH+)). The ultrasound fetal
      weight estimation was based on fetal abdominal circumference (EFW(AC)) using
      Campbell and Wilkins' equation. The correlation between the estimated fetal
      weight calculated using each of the formulae and the birth weight was then
      evaluated in Population B, and the diagnostic value of each of the methods for
      predicting birth weight <or=2500 g or >or=4000 g was also compared. RESULTS:
      EFW(AC) was better correlated with birth weight than was either EFW(FH) or
      EFW(FH+). With specificity set at 95%, the sensitivity of EFW(AC) in screening
      for neonates weighing <or=2500 g was significantly higher than that of EFW(FH)
      (50.7% vs. 41.2%, P < 0.05) or EFW(FH+) (50.7% vs. 40.4%, P < 0.05). Similarly,
      its sensitivity for predicting a birth weight of >or=4000 g was significantly
      higher than that of EFW(FH) (54.0% vs. 37.1%, P < 0.05) or EFW(FH+) (54.0% vs.
      45.1%, P < 0.05). CONCLUSIONS: Sonographic measurement of fetal abdominal
      circumference predicts high and low birth weight better than does clinical
      examination based on fundal height in routine practice between 37 and 41 weeks'
      gestation.

PMID- 19582802
TI  - Pronounced stereospecificity of (1)H, (13)C, (15)N and (77)Se shielding constants
      in the selenophenyl oximes as shown by NMR spectroscopy and GIAO calculations.
AB  - In the (1)H and (13)C NMR spectra of 1-(2-selenophenyl)-1-alkanone oximes, the
      (1)H, the (13)C-3 and (13)C-5 signals of the selenophene ring are shifted by 0.1
      0.4, 2.5-3.0 and 5.5-6.0 ppm, respectively, to higher frequencies, whereas those
      of the (13)C-1, (13)C-2 and (13)C-4 carbons are shifted by 4-5, approximately 11
      and approximately 1.7 ppm to lower frequencies on going from the E to Z isomer.
      The (15)N chemical shift of the oximic nitrogen is larger by 13-16 ppm in the E
      isomer relative to the Z isomer. An extraordinarily large difference (above 90
      ppm) between the (77)Se resonance positions is revealed in the studied oxime
      isomers, the (77)Se peak being shifted to higher frequencies in the Z isomer. The
      trends in the changes of the measured chemical shifts are well reproduced by the
      GIAO calculations of the (1)H, (13)C, (15)N and (77)Se shielding constants in the
      energy-favorable conformation with the syn orientation of the-C=N-O-H group
      relative to the selenophene ring.

PMID- 19582800
TI  - Disparities in mental health between rural and nonrural cancer survivors: a
      preliminary study.
AB  - OBJECTIVE: While much research has sought to identify disparities in cancer
      incidence, survival, and treatment, little research has sought to identify
      disparities in mental health (MH) outcomes among cancer survivors. The present
      study aims to identify disparities in MH outcomes between rural and nonrural
      cancer survivors. METHODS: Cancer survivors who met eligibility criteria were
      identified through the Kentucky SEER Cancer Registry. Rural status was determined
      by 2003 USDA Rural-Urban Continuum Codes. 116 (n=54 rural, 62 nonrural) survivors
      with diagnoses of breast (n=42), hematologic (n=39), or colorectal (n=35) cancer
      completed mail-back questionnaires and/or a telephone interview. RESULTS: Rural
      cancer survivors reported poorer MH functioning (effect size (ES)=0.45 SD),
      greater symptoms of anxiety (ES=0.70) and depression (ES=0.47), greater distress
      (ES=0.41), and more emotional problems (ES=0.47) than nonrural cancer survivors.
      Rural and nonrural cancer survivors did not differ consistently in regard to
      positive MH outcomes, such as benefit finding. The pattern of results was
      maintained when adjusted for education and physical functioning. CONCLUSIONS:
      Clinically important disparities in MH outcomes were evident between rural and
      nonrural cancer survivors. Interventions aimed at raising access and utilization
      of MH services may be indicated for cancer survivors in rural areas.

PMID- 19582804
TI  - Clonal B-cell population in a reactive lymph node in acquired immunodeficiency
      syndrome.
AB  - A 40-year-old female, HIV positive, stage C, since 4 years, complained of a right
      cervical lymph node swelling. Two years before, the patient had been diagnosed
      with follicular B-cell non-Hodgkin lymphoma (FL); she had been treated with four
      cycles of multiagent chemotherapy plus rituximab, the last cycle being
      administered 10 months before coming to our attention. An ultrasound (US) guided
      fine-needle cytology (FNC) showed an atypical lymphoid cell proliferation. The
      phenotype evidenced by flow cytometry (FC) analysis was D5: 10%, CD19: 49%, CD23:
      10%, FMC7: 0%, CD10: 40%, CD10/19: 40%, lambda light chain 40%, kappa light chain
      0%. FDG-positron emission tomography (PET/CT) scan showed positivity in the
      corresponding cervical area. Since low LDH values and a reduced lymph node size
      were observed, the lymph node was therefore excised; the histology revealed a
      reactive hyperplastic lymph node with florid follicular pattern. A subsequent PCR
      analysis, performed on DNA extracted from a whole histological section, did not
      evidence IgH rearrangement. The patient is currently undergoing strict clinical
      and instrumental follow-up, including PET every 3 months; after 13 months, she is
      alive without recurrence of lymphoma. Clonal B-cell populations in non
      lymphomatous processes have been described in mucosa-associated lymphoid cell
      populations and reactive lymph nodes, and are considered non-malignant, antigen
      driven, proliferations of B-lymphocytes determined by an abnormal response to
      bacterial or viral antigen stimulation. The present case occurred in an HIV
      patient and was clinically complex because of the patient's history of FL. This
      experience suggests much attention in the evaluation of radiological,
      cytological, and FC data and in clinical correlation in patients suffering from
      autoimmune or immunodeficiency syndromes.

PMID- 19582803
TI  - Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with
      chronic hepatitis C.
AB  - Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin
      resistance, but the extent of impairment in insulin action, the target pathways
      involved, and the role of the virus per se have not been defined. In this study,
      we performed a euglycemic hyperinsulinemic clamp (1 mU x minute(-1) x kg(-1))
      coupled with infusion of tracers ([6,6-(2)H(2)]glucose, [(2)H(5)]glycerol) and
      indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not
      to have any features of the metabolic syndrome, and in seven healthy controls. We
      also measured liver expression of inflammatory cytokines/mediators and tested
      their association with the metabolic parameters. Compared to controls, in
      patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25%
      lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal
      endogenous glucose production (EGP) was 20% higher (P = 0.011) and its
      suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol
      appearance was not different in the basal state or during the clamp, but lipid
      oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher
      in patients with CHC who had more steatosis and was directly related to EGP, TGD,
      and glucose oxidation. The decreased insulin-stimulated suppression of EGP was
      associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P <
      0.05) and interleukin-18 (P < 0.05) expression. CONCLUSION: Hepatitis C infection
      per se is associated with peripheral and hepatic insulin resistance. Substrate
      competition by increased lipid oxidation and possibly enhanced hepatic expression
      of inflammatory cytokines/mediators could be involved in the defective glucose
      regulation.

PMID- 19582805
TI  - Cytologic detection of Strongyloides stercoralis in a 55-year-old Hispanic man
      with routine rectal/anal pap smear.
AB  - The anal-rectal cytology is introduced recently to evaluate human-papillomavirus
      related cellular changes in the cells of anal canal. It is especially useful in
      high risk patients such as HIV patients. Very few reports were published
      regarding cytomorphological findings in anal cytology. Strongyloides stercoralis
      is an enteric helminthic parasite with particular significance in
      immunocompromised patients. The infection is asymptomatic or manifests as mild
      gastrointestinal symptoms in normal hosts. The infection can be devastating in
      immunocompromised persons, and carries a high mortality rate. The presence of S.
      stercoralis larva in anal-rectal pap smears is rare. We report a case in a
      routine anal-rectal Pap smear with Strongyloides, and discuss the clinical
      significance and life cycle of S. stercoralis.

PMID- 19582806
TI  - Imprint cytology of hepatosplenic suppurative candidal granuloma complicating
      acute leukaemia: three case reports.

PMID- 19582807
TI  - Fine needle aspiration cytology in a case of fibrous dysplasia of jaw.
AB  - Fibro-osseous lesions of the jaw comprise of a spectrum of diseases which include
      osseous dysplasia, fibrous dysplasia, and ossifying fibroma. The differentiation
      amongst these individual pathological lesions is difficult and a combined clinico
      radiological and histological correlation is essential for exact categorization.
      Fine needle aspiration cytology (FNAC) is frequently carried out to distinguish
      between benign and malignant lesions of the jaw as is a quick and reliable
      modality of investigation which guides in further management. We report, a case
      of a jaw swelling in a young male, diagnosed as fibrous dysplasia on FNAC.

PMID- 19582808
TI  - Endometrial glandular and stromal breakdown, part 3: cytomorphology of "condensed
      cluster of stromal cells".
AB  - The aim of this study was undertaken to clarify the cytological characteristic of
      the "condensed clusters of stromal cells," which may be recognized in endometrial
      glandular and stromal breakdown (EGBD) cases. The material consists of 60 cases
      of cytologic smears for which histopathological diagnosis was obtained by
      endometrial curettage; they comprised 30 cases of EGBD and 30 cases of
      endometrioid adenocarcinoma grade 1 (G1). The following parameters were examined
      for "condensed clusters of stromal cells" in EGBD and for "clumps of cancer
      cells" in G1, respectively: (1) the occurrence of "condensed clusters of stromal
      cells"; (2) the nuclear shape; (3) a longer/shorter axis ratio in cell nuclei;
      (4) the area of cell nuclei; (5) the presence of overlapping nuclei; (6) nuclear
      crowding; (7) immunostaining. (1)"Condensed clusters of stromal cells" were only
      observed in EGBD. (2) A reniform nuclear shape was observed in 100% EGBD (P <
      0.0001) in comparison to G1 (3%). (3) The longer/shorter axis ratio in cell
      nuclei, G1 (1.37 +/- 0.2) was significantly lower in comparison to EGBD (1.53 +/-
      0.12, P = 0.0005). (4) Nuclear area in G1 (51.6 +/- 11.9, P < 0.0001) was
      significantly higher in comparison to EGBD (24.3 +/- 3.9 microm(2)). (5) The
      score of overlapping nuclei in EGBD (2.5 +/- 0.49) was significantly higher in
      comparison to G1 (1.8 +/- 0.44, P < 0.0001). (6) The nuclear crowding score was
      the same both in EGBD (2) and G1 (2) and these findings were not statistically
      significant. (7) Both CD10 and Wilms' tumor protein 1 were positive in the
      "condensed clusters of stromal cells" in the EGBD. The anti-cytokeratin staining
      was positive in "clumps of cancer cells" in the G1. The evaluation of the
      immunocytochemical findings by combining the Wilms' tumor 1 protein, CD10, and
      the anti-cytokeratin with the considered cytomorphologic features (reniform
      nucleus) may be useful for a correct diagnosis of EGBD in endometrial cytology.

PMID- 19582809
TI  - Metastatic hepatocellular carcinoma presenting as a pancreatic mass by computed
      tomography scan and mimicking a primary neuroendocrine tumor: a potential pitfall
      in aspiration cytology.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting
      at late stage and portending a poor prognosis for the patient. The peripancreatic
      fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic
      primary pancreatic neoplasms, even in this location. It is crucial to be aware of
      this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and
      to develop a strategy to reach the correct diagnosis. We present an endoscopic
      ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a
      pancreatic mass radiologically that had neuroendocrine features on various
      cytological and histological preparations. The metastatic lesions were located
      surgically in the peripancreatic adipose tissue with involvement of one
      peripancreatic lymph node. This case illustrates the utility of FNA for
      diagnosing uncommon presentations of HCC and the importance of clinical history,
      cell block, and an immunocytochemical panel in determining the origin of the
      tumor.

PMID- 19582810
TI  - Cryptococcal yeast cells on a sputum smear.

PMID- 19582811
TI  - Orbital sarcoma in HIV positive patient: a diagnostic dilemma.
AB  - Diagnosis of a high-grade sarcoma on fine needle aspiration cytology (FNAC) may
      not pose any difficulty; however, further sub-typing is sometimes difficult. The
      clinical data, investigations, and finer points on cytomorphology may help for
      proper categorization of the tumor, however, we encountered a case of orbital
      sarcoma in an Human Immunodeficiency Virus (HIV) positive patient, in which
      further sub-typing was difficult even on histopathology and immunohistochemistry
      was helpful. The diagnostic difficulties on FNA cytology smears as well as
      histopathology are highlighted.

PMID- 19582812
TI  - The membrane-bound bile acid receptor TGR5 is localized in the epithelium of
      human gallbladders.
AB  - TGR5 (Gpbar-1) is a plasma membrane-bound, G protein-coupled receptor for bile
      acids. TGR5 messenger RNA (mRNA) has been detected in many tissues, including rat
      cholangiocytes and mouse gallbladder. A role for TGR5 in gallstone formation has
      been suggested, because TGR5 knockout mice did not develop gallstones when fed a
      lithogenic diet. In this study, expression and localization of TGR5 was studied
      in human gallbladders. TGR5 mRNA and protein were detected in all 19
      gallbladders. Although TGR5 mRNA was significantly elevated in the presence of
      gallstones, no such relation was found for TGR5 protein levels. In order to study
      the localization of TGR5 in human gallbladders, a novel antibody was generated.
      The receptor was localized in the apical membrane and the rab11-positive
      recycling endosome of gallbladder epithelial cells. Furthermore, the TGR5
      staining colocalized with the cyclic adenosine monophosphate-regulated chloride
      channel cystic fibrosis transmembrane conductance regulator (CFTR) and the apical
      sodium-dependent bile salt uptake transporter, suggesting a functional coupling
      of TGR5 to bile acid uptake and chloride secretion. Stimulation with bile acids
      significantly increased cyclic adenosine monophosphate concentration in human
      gallbladder tissue. Incubation of gallbladder epithelial cells with a TGR5
      agonist led to a rise of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide
      (MQAE)-fluorescence, suggestive of a decrease in intracellular chloride
      concentration. The TGR5 agonist-dependent increase in MQAE-fluorescence was
      absent in TGR5 knockout mice or in the presence of a CFTR inhibitor, indicating
      that TGR5 mediates chloride secretion via activation of CFTR. The presence of the
      receptor in both the plasma membrane and the recycling endosome indicate that
      TGR5 can be regulated by translocation. CONCLUSION: The data suggest a role for
      TGR5 in bile acid-induced fluid secretion in biliary epithelial cells.

PMID- 19582813
TI  - Interleukin-27 displays interferon-gamma-like functions in human hepatoma cells
      and hepatocytes.
AB  - Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family.
      It is secreted by antigen-presenting cells, strongly acts on T cells, and also
      stimulates innate immune cells. In most studies, the effects of IL-27 on T cells
      were investigated; however, not much is known about possible effects of IL-27 on
      other cell types. IL-27 signals via the common IL-6-type cytokine receptor chain
      gp130 and the IL-27-specific chain WSX-1. Given the importance of gp130 in
      regulating liver responses such as the acute phase response or liver
      regeneration, we investigated whether IL-27 could also have a function in liver
      cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a
      sustained signal transducer and activator of transcription (STAT)1 and STAT3
      activation. Whereas the STAT3 mediated responses to IL-27 (gamma-fibrinogen and
      hepcidin induction) are not detectable, we observe an interferon-gamma (IFN
      gamma)-like STAT1 response leading to the induction of interferon-regulated
      proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9,
      myxovirus resistance A and guanylate binding protein 2. CONCLUSION: Our study
      provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and
      shows that IL-27 responses are not restricted to the classical immune cells. Our
      results suggest that IL-27 exerts IFN-like functions in liver cells and that it
      can contribute to the antiviral response in these cells.

PMID- 19582814
TI  - Cytopatholologic features of gliosarcoma with areas of primitive neuroepithelial
      differentiation of the brain in squash smears.
AB  - Gliosarcoma with areas of primitive neuroepithelial differentiation (GSPNED) is
      an extremely rare neoplasm. A case is presented here in which squash smears of a
      left temporal lobe tumor in a 76-year-old male demonstrated two distinct and
      easily recognizable cellular populations, i.e., densely hyperchromatic cells of a
      primitive nature in a fibrillary background and pleomorphic spindle-shaped cells.
      Occasional pseudo-rosette formations and nuclear cannibalism suggestive of
      neuroendocrine differentiation were also found. A cytologic diagnosis of a
      malignant tumor was suggested, and histochemical and immunohistochemical studies
      were conducted on formalin-fixed, paraffin-embedded material. Reticulin stain
      highlighted increased intercellular collagen and reticulin deposition within the
      spindled regions, whereas nodules with primitive cells were reticulin-poor. There
      was a diffuse and strong reactivity to neuron specific enolase, synaptophysin and
      CD56 immunostains. A stain for glial fibrillary acidic protein and S-100 protein
      demonstrated a subset of tumor cells including elongated cytoplasmic processes.
      The spindled component was positive for vimentin and smooth muscle actin, whereas
      the primitive-appearing tumor cells were negative. The diagnosis of GSPNED was
      confirmed based on cytopathologic, histopathological and immunohistochemical
      results. The cytomorphologic features of this distinctive tumor are illustrated,
      and the adjunctival value of squash smears for frozen-section diagnosis is also
      discussed. This is the first presentation of a cytopathologic analysis that
      provides an important clue to an accurate diagnosis of GSPNED.

PMID- 19582815
TI  - Cytology of head and neck squamous cell carcinoma variants.
AB  - The most common diagnosis rendered with head and neck fine needle aspiration
      (FNA) biopsy is metastatic squamous cell carcinoma (SCC). While most cases of
      metastatic SCC pose little diagnostic difficulty, the diagnosis of metastatic
      histologic variants of SCC, often coupled with less common etiologies, can be
      more problematic. This manuscript reviews the clinicopathologic features of the
      histologic variants of upper aerodigestive tract SCC (verrucous, papillary,
      spindle cell, undifferentiated, acantholytic, and basaloid) and uncommon
      etiologies of head and neck SCC (human papillomavirus, Epstein-Barr Virus, and
      NUT midline carcinomas). Particular attention is paid to the cytologic features
      of these lesions. Differential diagnoses and the use of ancillary testing are
      discussed.

PMID- 19582816
TI  - MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone
      morphogenetic protein signaling and liver stem cell differentiation by targeting
      Smads.
AB  - Transforming growth factor-beta / bone morphogenetic protein (TGFbeta/BMP)
      signaling has a gradient of effects on cell fate choice in the fetal mouse liver.
      The molecular mechanism to understand why adjacent cells develop into bile ducts
      or grow actively as hepatocytes in the ubiquitous presence of both TGFbeta
      ligands and receptors has been unknown. We hypothesized that microRNAs (miRNAs)
      might play a role in cell fate decisions in the liver. miRNA profiling during
      late fetal development in the mouse identified miR-23b cluster miRNAs comprising
      miR-23b, miR-27b, and miR-24-1 and miR-10a, miR-26a, and miR-30a as up-regulated.
      In situ hybridization of fetal liver at embryonic day 17.5 of gestation revealed
      miR-23b cluster expression only in fetal hepatocytes. A complementary (c)DNA
      microarray approach was used to identify genes with a reciprocal expression
      pattern to that of miR-23b cluster miRNAs. This approach identified Smads
      (mothers against decapentaplegic homolog), the key TGFbeta signaling molecules,
      as putative miR-23b cluster targets. Bioinformatic analysis identified multiple
      candidate target sites in the 3' UTRs (untranslated regions) of Smads 3, 4, and
      5. Dual luciferase reporter assays confirmed down-regulation of constructs
      containing Smad 3, 4, or 5, 3' UTRs by a mixture of miR-23b cluster mimics.
      Knockdown of miR-23b miRNAs during hepatocytic differentiation of a fetal liver
      stem cell line, HBC-3, promoted expression of bile duct genes, in addition to
      Smads, in these cells. In contrast, ectopic expression of miR-23b mimics during
      bile duct differentiation of HBC-3 cells blocked the process. CONCLUSION: Our
      data provide a model in which miR-23b miRNAs repress bile duct gene expression in
      fetal hepatocytes while promoting their growth by down-regulating Smads and
      consequently TGFbeta signaling. Concomitantly, low levels of the miR-23b miRNAs
      are needed in cholangiocytes to allow TGFbeta signaling and bile duct formation.

PMID- 19582818
TI  - Fine-needle aspiration (FNA) and pleural fluid cytology diagnosis of benign
      metastasizing pleomorphic adenoma of the parotid gland in the lung: a case report
      and review of literature.
AB  - Lesions that contain abundant benign myoepithelial cells, including pleomorphic
      adenomas of salivary gland origin, may present a diagnostic challenge in fine
      needle aspiration (FNA) specimens. Benign metastasizing pleomorphic adenoma is a
      rare neoplasm, in which the benign appearing pleomorphic adenoma, without any
      histological evidence of malignancy, metastasizes to distant sites including
      lung. In the absence of clinical history of a pre-existing myoepithelial
      neoplasm, the presence of myoepithelial cells in the lung or any other organs
      besides salivary glands may create diagnostic difficulty. Here we present the
      cytologic findings of such a metastatic tumor found in the lung FNA and pleural
      fluid specimens from a 64-year-old woman, with a history of local recurrent
      salivary gland pleomorphic adenomas, who presented with multiple bilateral
      pulmonary nodules and pleural effusion. The diagnosis of benign metastasizing
      pleomorphic adenoma was made based on clinical information and cytomorphology,
      and confirmed by immunocytochemistry.

PMID- 19582819
TI  - Cytopathological diagnosis of adult retinoblastoma in a vitrectomy specimen.
AB  - Retinoblastoma (RB) is extremely rare in adults. We describe a case of RB
      diagnosed by cytology in a vitrectomy specimen of a 23-year-old patient who
      presented with diminished visual acuity and retinal detachment in the absence of
      a clinically-visible mass. Cytological examination of the vitreous fluid showed
      clusters of loosely cohesive atypical cells with high nuclear to cytoplasmic
      ratio and "salt and pepper" chromatin pattern in a background of normal neuronal
      retinal cells. Nuclear molding was present as well as numerous apoptotic bodies.
      The cells were focally positive for epithelial markers and showed strong and
      diffuse positivity for neuroendocrine markers. Ki-67 stained 90% of the "atypical
      cells" nuclei, in contrast to nonneoplastic retinal neuronal cells, which were
      negative for the marker. A diagnosis of RB was rendered, and subsequently was
      confirmed in the enucleation specimen. The cytological differential diagnosis is
      discussed as well as the role that cytology and immunohistochemistry can play in
      differentiating neoplastic cells from normal retinal cellular elements in
      vitreous fluid specimens.

PMID- 19582817
TI  - Impaired liver regeneration in mice lacking glycine N-methyltransferase.
AB  - Hepatic S-adenosylmethionine (SAMe) is maintained constant by the action of
      methionine adenosyltransferase I/III (MATI/III), which converts methionine into
      SAMe and glycine N-methyltransferase (GNMT), which eliminates excess SAMe to
      avoid aberrant methylation reactions. During liver regeneration after partial
      hepatectomy (PH) MATI/III activity is inhibited leading to a decrease in SAMe.
      This injury-related reduction in SAMe promotes hepatocyte proliferation because
      SAMe inhibits hepatocyte DNA synthesis. In MATI/III-deficient mice, hepatic SAMe
      is reduced, resulting in uncontrolled hepatocyte growth and impaired liver
      regeneration. These observations suggest that a reduction in SAMe is crucial for
      successful liver regeneration. In support of this hypothesis we report that liver
      regeneration is impaired in GNMT knockout (GNMT-KO) mice. Liver SAMe is 50-fold
      higher in GNMT-KO mice than in control animals and is maintained constant
      following PH. Mortality after PH was higher in GNMT-KO mice than in control
      animals. In GNMT-KO mice, nuclear factor kappaB (NFkappaB), signal transducer and
      activator of transcription-3 (STAT3), inducible nitric oxide synthase (iNOS),
      cyclin D1, cyclin A, and poly (ADP-ribose) polymerase were activated at baseline.
      PH in GNMT-KO mice was followed by the inactivation of STAT3 phosphorylation and
      iNOS expression. NFkappaB, cyclin D1 and cyclin A were not further activated
      after PH. The LKB1/AMP-activated protein kinase/endothelial nitric oxide synthase
      cascade was inhibited, and cytoplasmic HuR translocation was blocked despite
      preserved induction of DNA synthesis in GNMT-KO after PH. Furthermore, a
      previously unexpected relationship between AMPK phosphorylation and NFkappaB
      activation was uncovered. CONCLUSION: These results indicate that multiple
      signaling pathways are impaired during the liver regenerative response in GNMT-KO
      mice, suggesting that GNMT plays a critical role during liver regeneration,
      promoting hepatocyte viability and normal proliferation.

PMID- 19582820
TI  - Modification of approach for totally implantable venous access device decreases
      rate of complications.
AB  - BACKGROUND: The aim of this study was to analyze the potential utilization of
      external jugular vein (EJV) cutdown approach for totally implantable venous
      access device (TIVAD) placement. METHODS: This is a prospective, non-randomized,
      observational, uni-institutional study. All patients (n = 451) were first
      subjected to attempted subclavian vein (SV) percutaneous approach. If SV
      percutaneous approach was unsuccessful after multiple puncture in group A and
      maximum two puncture in group B, an ipsilateral EJV cutdown approach was
      attempted. RESULTS: Four hundred four patients (89.6%) underwent TIVAD placement
      via SV percutaneous approach. Of those 47 patients in which SV percutaneous
      approach was not successful, 8 patients in group A and 39 patients in group B,
      TIVAD was placed via ipsilateral EJV cutdown approach. The average of operative
      time was 17.9 +/- 8.5 min in group A and 18 +/- 7.3 min in group B (P > 0.05).
      The early complications of group A were significantly higher than that of group B
      (P = 0.02). CONCLUSIONS: TIVAD placement by the SV percutaneous approach is safe
      and fast, and its success rate is very high. By avoiding the immediate
      complications associated with the percutaneous approach, the EJV cutdown has to
      be considered a valid, safe, and suitable alternative when the SV percutaneous
      approach unsuccessful after two needle puncture.

PMID- 19582821
TI  - Postoperative chemotherapy after neoadjuvant chemoradiation and surgery for
      rectal cancer: is it essential for patients with ypT0-2N0?
AB  - BACKGROUND: The potential advantage of adjuvant chemotherapy in patients with
      ypT0-2N0 rectal cancer remains unclear. The purpose of this study was to evaluate
      whether this therapy has an impact on survival. MATERIALS AND METHODS: Patients
      who underwent curative surgery after preoperative chemoradiation for locally
      advanced low rectal cancer were retrospectively reviewed. A total of 41
      consecutive patients with pathological stage 0 (ypT0N0) or I (ypT1-2N0) were
      enrolled. Of the 41 patients, 17 (41.5%) received postoperative 5-fluorouracil (5
      FU)-based chemotherapy, while 24 were followed without postoperative therapy.
      Oncologic outcomes were compared between the two groups. RESULTS: The median
      follow-up period was 47.6 months. The overall postoperative complication rates
      did not differ significantly between the patients who received chemotherapy and
      those who did not (17.6% vs. 20.8%, P = 0.799). The 5-year overall and disease
      free survival rates for patients who received chemotherapy were 88.9% and 84.7%,
      which were not significantly different from the rates for those who did not
      (85.9%; P = 0.644 and 73.4%; P = 0.599, respectively). CONCLUSIONS: Postoperative
      adjuvant chemotherapy for patients with good responses after preoperative
      chemoradiation and curative surgery did not significantly improve the survival.
      However, this should be validated in prospective randomized trials with larger
      sample sizes.

PMID- 19582822
TI  - Laparoscopic versus open gastrectomy for gastric cancer patients with COPD.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a
      higher risk of developing postoperative pulmonary complications. Laparoscopic
      gastrectomy (LG) is accepted as a standard treatment for early gastric cancer. We
      sought to compare the clinical presentation and complications associated with LG
      and open gastrectomy (OG) to define the role of LG in the treatment of patients
      with gastric cancer and COPD. METHODS: This was a retrospective cohort study of
      patients with gastric cancer and COPD who underwent gastrectomy from January 2005
      to December 2007. Patients were divided into LG group and OG group according to
      the treatment guidelines. The stage of COPD was determined by the FEV1 ratio.
      RESULTS: There were 104 patients enrolled in this study. No significant
      differences were observed in preoperative pulmonary function between the two
      groups, and most patients (99/104, 95%) were in COPD stages I and II. The changes
      in end-tidal CO(2) (P = 0.012) and PaCO(2) (P < 0.001) during surgery were
      statistically significant in the LG group. There were no significant differences
      in incidence of postoperative pulmonary complications between the LG (5/61, 8%)
      and OG (4/43, 9%) groups. CONCLUSIONS: LG can be performed safely for patients
      with gastric cancer and COPD in stage I and II.

PMID- 19582823
TI  - The perforator angiosome: a new concept in the design of deep inferior epigastric
      artery perforator flaps for breast reconstruction.
AB  - BACKGROUND: The previously described "perfusion zones" of the abdominal wall
      vasculature are based on filling of the deep inferior epigastric artery (DIEA)
      and all its branches simultaneously. With the advent of the DIEA perforator flap,
      only a single or several perforators are included in supply to the flap. As such,
      a new model for abdominal wall perfusion has become necessary. The concept of a
      "perforator angiosome" is thus explored. METHODS: A clinical and cadaveric study
      of 155 abdominal walls was undertaken. This comprised the use of 10 whole,
      unembalmed cadaveric abdominal walls for angiographic studies, and 145 abdominal
      wall computed tomographic angiograms (CTAs) in patients undergoing preoperative
      imaging of the abdominal wall vasculature. The evaluation of the subcutaneous
      branching pattern and zone of perfusion of individual DIEA perforators was
      explored, particularly exploring differences between medial and lateral row
      perforators. RESULTS: Fundamental differences exist between medial row and
      lateral row perforators, with medial row perforators larger (1.3 mm vs. 1 mm) and
      more likely to ramify in the subcutaneous fat toward the contralateral
      hemiabdomen (98% of cases vs. 2% of cases). A model for the perfusion of the
      abdominal wall based on a single perforator is presented. CONCLUSION: The
      "perforator angiosome" is dependent on perforator location, and can mapped
      individually with the use of preoperative imaging.

PMID- 19582824
TI  - A new approximator used in microvascular anastomosis.

PMID- 19582825
TI  - Income and attrition in the treatment of depression: a STAR*D report.
AB  - BACKGROUND: Attrition, or dropping out of treatment, remains a major issue in the
      care of depressed outpatients. Whether different factors are associated with
      attrition for different socioeconomic groups is not known. This report assessed
      whether attrition rates and predictors of attrition differed among depressed
      outpatients with different income levels. METHODS: Outpatients with nonpsychotic
      major depressive disorder treated for up to 14 weeks with citalopram in the first
      step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study
      were divided by household incomes of <$20,000, $20,000-<$40,000, and >or=$40,000.
      Attrition rates and sociodemographic and clinical correlates of attrition were
      identified for each group. RESULTS: Regardless of income level, remission rates
      were lower for participants who dropped out of treatment. Attrition rates
      increased as income decreased. For all income levels, younger age was
      independently associated with attrition. For the lowest income level, less
      education, better mental health functioning, being on public insurance, and
      having more concurrent Axis I conditions were associated with a greater
      likelihood of attrition. For the middle income group, less education, better
      mental health functioning, being Black or of another non-White race, and
      treatment in a psychiatric versus primary-care setting predicted greater
      attrition. For the highest income group, being Hispanic, having a family history
      of drug abuse, and melancholic features predicted attrition. Atypical symptom
      features (middle income group) and recurrent depression (highest income group)
      were associated with retention. CONCLUSIONS: Efforts to retain patients in
      antidepressant treatment should focus especially on less educated patients with
      lower household incomes and younger patients.

PMID- 19582826
TI  - Killian-Jamieson diverticulum mimicking a suspicious thyroid nodule: sonographic
      diagnosis.
AB  - Killian-Jamieson diverticulum is a rare form of pharyngoesophageal diverticula
      emerging in the anterolateral wall of the cervical esophagus. We present a case
      of Killian-Jamieson diverticulum that mimicked a thyroid nodule on sonography
      (US), and for which a US-guided fine-needle aspiration (FNA) was performed. The
      possibility of Killian-Jamieson diverticulum should be considered when a thyroid
      nodule is seen adjacent to the esophagus even without US change during/after
      swallowing.

PMID- 19582827
TI  - Safety and diagnostic accuracy of percutaneous ultrasound-guided biopsy of the
      spleen: a multicenter study.
AB  - PURPOSE: To analyze the safety and accuracy of ultrasound-guided (USG)
      percutaneous needle biopsy of the spleen. METHODS: Sixty-two USG needle biopsies
      performed in 52 patients were retrospectively analyzed: there were 53 biopsies of
      local lesions and 9 biopsies of diffuse lesions. Fine-needle aspiration (FNA) was
      performed in 37 cases and core-needle biopsy (CNB) in 25 cases. The complications
      and diagnostic accuracy of the 2 types of biopsy were compared. RESULTS: Two
      patients (3.8%) had postprocedural hemorrhage after CNB; one was minor, and the
      other severe, requiring splenectomy. No bleeding occurred with FNA. The
      diagnostic accuracy was similar with FNA (86.5%) and CNB (92%), whereas in
      patients with lymphoma, accuracy of FNA (80%) tended to be lower than that of CNB
      (100%), although the difference was not statistically significant. CONCLUSION:
      USG needle biopsy is safe and effective for diagnosing both focal and diffuse
      splenic lesions. The risk of bleeding may be lower with FNA than with CNB.

PMID- 19582828
TI  - Middle cerebral artery peak systolic velocity and ductus venosus velocity in the
      investigation of nonimmune hydrops.
AB  - PURPOSE: This study was performed to investigate the cause of nonimmune hydrops
      fetalis by measuring the peak systolic velocity (PSV) in the middle cerebral
      artery (MCA) and velocity waveforms of the ductus venosus (DV) with Doppler.
      METHODS: This cross-sectional study was done on 19 pregnancies referred to three
      university teaching hospitals for further investigation of nonimmune hydrops
      fetalis in 2007 and 2008. The MCA-PSV and DV velocity waveforms were recorded in
      all fetuses. Anemia was investigated in cases with MCA-PSV values greater than
      1.50 MoM (multiple of the median). Cardiovascular causes and chromosomal
      abnormalities were investigated in fetuses with abnormal DV velocity. RESULTS:
      Four of 19 fetuses had MCA-PSV values greater than 1.50 MoM. The causes of anemia
      were cytomegalovirus, parvovirus B19 infections, congenital heart disease, and
      Turner syndrome. Four cases had reversed flow in the DV; three of them had
      congenital heart disease on echocardiography; and one had a normal
      echocardiogram, but an abnormal karyotype was detected. CONCLUSION: Assessment of
      the MCA-PSV and DV velocity waveforms during sonographic examination of fetuses
      with nonimmune hydrops fetalis may improve our knowledge about the etiology of
      this condition.

PMID- 19582829
TI  - Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia
      by conventional cytogenetics using CpG oligonucleotide and interleukin-2
      stimulation: A Belgian multicentric study.
AB  - We performed a multicentric study to assess the impact of two different culture
      procedures on the detection of chromosomal abnormalities in 217 consecutive
      unselected cases with chronic lymphocytic leukemia (CLL) referred for routine
      analysis either at the time of diagnosis (n = 172) or during disease evolution (n
      = 45). Parallel cultures of peripheral blood or bone marrow were set up with the
      addition of either the conventional B-cell mitogen 12-O-tetradecanoyl-phorbol-13
      acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin-2 (IL
      2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities
      were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was
      detected in both cultures. Among these, the percentages of aberrant metaphases
      were similar in both conditions in 17 cases, higher in the CpG/IL-2 culture in 43
      cases, and higher in the TPA culture in 18 cases. Clonal aberrations were
      detected in only one culture, either in CpG/IL-2 or TPA in 33 (15%) and 5 (2%)
      cases, respectively. Taken together, abnormal karyotypes were observed in 51%
      with CpG/IL-2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201)
      allowed the detection of abnormalities not visible by conventional cytogenetic
      analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q)
      (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL-2
      stimulation increases the detection rate of chromosomal abnormalities in CLL
      compared with TPA and that further improvement can be obtained by FISH. However,
      neither conventional cytogenetics nor FISH detected all aberrations,
      demonstrating the complementary nature of these techniques.

PMID- 19582830
TI  - Freezing reaction in panic disorder patients associated with anticipatory
      anxiety.
AB  - BACKGROUND: Anticipatory anxiety can be described as a conditioned response with
      a defensive posture of freezing and autonomic activation. The purpose of this
      study was to assess the postural control analysis and autonomic activation in
      panic disorder (PD) patients presented with visual stimuli. METHODS: PD patients
      (n=29) and healthy controls (n=27) stood on a force platform while viewing a
      series of anxiogenic, mutilation, and neutral pictures. Skin conductance
      responses and the displacements of the center of pressure were measured. RESULTS:
      Overall, the PD patients demonstrated significantly reduced body sway, increased
      mean power frequency, and increased skin conductance compared to control group
      throughout the experiment (P<.05). PD patients also showed a negative correlation
      between anticipatory anxiety and mean sway area throughout the experiment.
      However, there was no significant difference in body sway velocity compared to
      healthy controls while viewing the anxiogenic block of pictures or the neutral
      block. CONCLUSIONS: Our data shows that PD patients experiencing anticipatory
      anxiety may present with lower mobility, consistent with the freezing behavior of
      the defense cascade. The data also shows that PD patients do not have a postural
      instability when confronted with specific anxiogenic context. The importance of
      this study is that it objectively demonstrates freezing-like behavior in PD
      patients.

PMID- 19582831
TI  - New methods for chicken embryo manipulations.
AB  - The capacity to image a growing embryo while simultaneously studying the
      developmental function of specific molecules provides invaluable information on
      embryogenesis. However, until recently, this approach was accomplished with
      difficulty both because of the advanced technology needed and because an easy
      method of minimizing damage to the embryo was unavailable. Here, we present a
      novel way of adapting the well-known EC culture of whole chick embryos to time
      lapse imaging and to functional molecular studies using blocking agents. The
      novelty of our method stems from the ability to apply blocking agents ex ovo as
      well as in ovo. We were able to study the function of a set of molecules by
      culturing developing embryos ex ovo in tissue culture media containing these
      molecules or by injecting them underneath the live embryo in ovo. The in ovo
      preparation is particularly valuable, because it extends the period of time
      during which the developmental function of the molecule can be studied and it
      provides an easy, reproducible method for screening a batch of molecules. These
      new techniques will prove very helpful in visualizing and understanding the role
      of specific molecules during embryonic morphogenesis, including blood vessel
      formation.

PMID- 19582832
TI  - Antibacterial effects and dissolution behavior of six bioactive glasses.
AB  - Dissolution behavior of six bioactive glasses was correlated with the
      antibacterial effects of the same glasses against sixteen clinically important
      bacterial species. Powdered glasses (<45 microm) were immersed in simulated body
      fluid (SBF) for 48 h. The pH in the solution inside the glass powder was measured
      in situ with a microelectrode. After 2, 4, 27, and 48 h, the pH and concentration
      of ions after removing the particles and mixing the SBF were measured with a
      normal glass pH electrode and ICP-OES. The bacteria were cultured in broth with
      the glass powder for up to 4 days, after which the viability of the bacteria was
      determined. The antibacterial effect of the glasses increased with increasing pH
      and concentration of alkali ions and thus with increased dissolution tendency of
      the glasses, but it also depended on the bacterium type. The changes in the
      concentrations of Si, Ca, Mg, P, and B ions in SBF did not show statistically
      significant influence on the antibacterial property. Bioactive glasses showed
      strong antibacterial effects for a wide selection of aerobic bacteria at a high
      sample concentration (100 mg/mL). The antibacterial effects increased with glass
      concentration and a concentration of 50 mg/mL (SA/V 185 cm(-1)) was required to
      generate the bactericidal effects. Understanding the dissolution mechanisms of
      bioactive glasses is essential when assessing their antibacterial effects.

PMID- 19582833
TI  - Angiogenic and inflammatory host response to surgical meshes of different mesh
      architecture and polymer composition.
AB  - One of the major challenges in hernia repair is the development of surgical
      meshes that guarantee an optimal biocompatibility and incorporation into the host
      tissue. For this purpose, it is necessary to study the impact of different mesh
      types on angiogenesis, inflammation, and tissue formation. In the present study,
      we analyzed the host tissue reaction to Prolene, Ultrapro, and Vicryl meshes over
      a 14-day period after implantation into the hamster dorsal skinfold chamber using
      intravital fluorescence microscopy and histology. Our results demonstrate that
      compared with the Prolene and Ultrapro mesh, the Vicryl mesh induced a more
      pronounced angiogenic and inflammatory host tissue response with formation of a
      densely vascularized granulation tissue, which was infiltrated by many
      inflammatory cells. However, the strong foreign body reaction was not associated
      with a better mesh incorporation, but resulted in a significantly reduced
      explantation strength when compared with that of Prolene and Ultrapro meshes.
      Histological examinations revealed that the granulation tissue surrounding the
      Vicryl mesh was instable, because of low collagen content and massive
      infiltration of inflammatory cells. Thus, our data demonstrate that a stronger
      angiogenic and inflammatory response to an implanted mesh does not necessarily
      result in a better incorporation into the host tissue.

PMID- 19582834
TI  - Porcine gelatin microsphere/calcium phosphate cement composites: an in vitro
      degradation study.
AB  - Scaffolds for bone tissue engineering preferably should be mechanically stable,
      osteoconductive, biodegradable and porous. To comply with these characteristics,
      calcium phosphate cements (CPCs) with porcine (type A) gelatin microspheres were
      formulated. In this experiment, in vitro degradation of 10 wt % gelatin type A
      microsphere CPCs (GELA CPCs) was followed for 12 weeks in proteolytic medium.
      Results showed a gradual decrease in mass, compression strength and E-modulus.
      Morphology investigation showed that degradation of the spheres started at the
      surface of the composite and gradually proceeded to the inner part. Overall,
      porcine gelatin microspheres can be used to generate in situ macroporosity into
      an injectable CPC.

PMID- 19582835
TI  - Specific DNA G-quadruplexes bind to ethanolamines.
AB  - A significant number of G-quadruplex-forming sequences have been revealed in
      human genome by bioinformatic searches, implying that G-quadruplexes may be
      involved in important biological processes and may be new chemotherapeutic
      targets. Therefore, it is important to discover the potential interactions of G
      quadruplexes with other molecules or groups. Here we describe a class of G
      quadruplexes, which can bind to ethanolamine groups that widely exist in
      biomolecules and drug molecules. The specific interaction of these G-quadruplexes
      with ethanolamine groups was identified by high performance affinity
      chromatography (HPAC) using immobilized ethanolamine and diethanolamine as
      stationary phase reagents. The circular dichroism (CD) spectra and native
      polyacrylamide gel electrophoresis (PAGE) show that these ethanolamine binding
      quadruplexes adopt an intramolecularly parallel structure. The relationship of
      ethanolamine binding and G-quadruplexe structure provides new clues for the G
      quadruplex-related studies as well as for the molecular designs of therapeutic
      reagents.

PMID- 19582836
TI  - Field-based comparison of ligand and coactivator binding sites of nuclear
      receptors.
AB  - A structure-based comparison of the ligand-binding domains of 35 nuclear
      receptors from five different subfamilies is presented. Their ligand and
      coactivator binding sites are characterized using knowledge-based contact
      preference fields for hydrophobic and hydrophilic interactions implemented in the
      MOE modeling environment. Additionally, for polar knowledge-based field points
      the preference for negative or positive electrostatic interactions is estimated
      using the Poisson-Boltzmann equation. These molecular-interaction fields are used
      to cluster the nuclear receptor family based on similarities of their binding
      sites. By analyzing the similarities and differences of hydrophobic and polar
      fields in binding pockets of related receptors it is possible to identify
      conserved interactions in ligand and coactivator binding pockets, which support
      e.g. design of specific ligands during lead optimization or virtual screening as
      docking filter. Examples of remarkable similarities between ligand binding sites
      of members from phylogenetically different nuclear receptor families (RXR, RAR,
      HNF4, NR5) and differences between closely related subtypes (LXR, RAR, TR) are
      discussed in more detail. Significant similarities and differences of coactivator
      binding sites are shown for NR3Cs, LXRs and PPARs.

PMID- 19582838
TI  - Effects of alendronate on bone formation and osteoclastic resorption after
      implantation of beta-tricalcium phosphate.
AB  - The aim of this study was to determine the effects of alendronate (ALN) on
      osteoclastic resorption of beta-tricalcium phosphate (beta-TCP) and bone
      formation. beta-TCP blocks of 75% porosity, with or without ALN treatment, were
      implanted into cavities drilled in rabbit femoral condyles. New bone formation,
      residual amount of beta-TCP, and the number of tartrate-resistant acid
      phosphatase-positive cells were evaluated 2 weeks after surgery. The results show
      that local application of ALN at a concentration of 10(-2) to 10(-6)M reduced the
      number of osteoclasts on the surface of beta-TCP. New bone formation was also
      inhibited by ALN in a dose-dependent manner. Thus, inhibition of osteoclast
      formation resulted in reduced beta-TCP resorption and bone formation. These
      results suggest that osteoclast-mediated resorption plays an important role in
      bone formation and a coupling-like phenomenon could occur in beta-TCP-filled bone
      defects.

PMID- 19582839
TI  - Ectopic osteogenic ability of calcium phosphate scaffolds cultured with
      osteoblasts.
AB  - Bone substitute materials can induce bone formation when combined with
      mesenchymal stem cells (MSC). The aim of the current study was to examine in vivo
      ectopic bone formation with MSC on tricalcium phosphate (TCP) ceramics.
      Osteoblasts isolated from bone marrow stromal cells (BMSCs) of New Zealand
      rabbits were cultured with TCP ceramics for 10 days, followed by implantation of
      the cultured TCP ceramics into the rabbit dorsum muscle. The cultured TCP and in
      vivo new bone formation with TCP biodegradation were evaluated histologically.
      Scanning electron microscopy showed that the surface of the cultured TCP ceramics
      was filled by osteoblasts with a cell-free zone in the central area. New bone was
      formed on the cultured TCP ceramics with signs of gradual degradation of TCP
      ceramics at 8 weeks of implantation, indicating that TCP could be a potential
      scaffold for seeding cells used for development of bioengineering tissues.

PMID- 19582837
TI  - Poly-epsilon-caprolactone/gel hybrid scaffolds for cartilage tissue engineering.
AB  - The aim of this study was to determine the suitability of hybrid scaffolds
      composed of naturally derived biopolymer gels and macroporous poly-epsilon
      caprolactone (PCL) scaffolds for neocartilage formation in vitro. Rabbit
      articular chondrocytes were seeded into PCL/HA (1 wt % hyaluronan), PCL/CS (0.5
      wt % chitosan), PCL/F (1:3 fibrin sealant plus aprotinin), and PCL/COL1 (0.24%
      type I collagen) hybrids and cultured statically for up to 50 days. Growth
      characteristics were evaluated by histological analysis, scanning electron
      microscopy, and confocal laser scanning microscopy. Neocartilage was quantified
      using a dimethyl-methylene blue assay for sulfated glycosaminoglycans (sGAG) and
      an enzyme-linked immunosorbent assay for type II collagen (COL2), normalized to
      dsDNA content by fluorescent PicoGreen assay. Chondrocytes were homogenously
      distributed throughout the entire scaffold and exhibited a predominantly
      spheroidal shape 1 h after being seeded into scaffolds. Immunofluorescence
      depicted expanding proteoglycan deposition with time. The sGAG per dsDNA
      increased in all hybrids between days 25 and 50. PCL/HA scaffolds consistently
      promoted highest yields. In contrast, total sGAG and total COL2 decreased in all
      hybrids except PCL/CS, which favored increasing values and a significantly higher
      total COL2 at day 50. Overall, dsDNA content decreased significantly with time,
      and particularly between days 3 and 6. The PCL/HA hybrid displayed two
      proliferation peaks at days 3 and 25, and PCL/COL1 displayed one proliferation
      peak at day 12. The developed hybrids provided distinct short-term environments
      for implanted chondrocytes, with not all of them being explicitly beneficial
      (PCL/F, PCL/COL1). The PCL/HA and PCL/CS hybrids, however, promoted specific
      neocartilage formation and initial cell retention and are thus promising for
      cartilage tissue engineering.

PMID- 19582840
TI  - Development of an in vitro model on cellular adhesion on granular natural bone
      mineral under dynamic seeding conditions--a pilot study.
AB  - Adhesion of osteogenic cells on biomaterials can be studied with static in vitro
      models, whereas models representing dynamic seeding conditions are rare. Herein,
      we present an in vitro model to study cell adhesion on granular biomaterials
      under dynamic seeding conditions. Radiolabeled osteogenic MC3T3-E1 cells were
      allowed to adhere to granules of natural bovine bone mineral (NBM) under constant
      rotation. Adhesion of MC3T3-E1 cells was determined by liquid scintillation
      counting, and cell morphology was visualized by scanning electron microscopy.
      Cell viability was determined by MTT assay under static and dynamic conditions,
      at room and body temperature, and in the presence or absence of serum. We show
      here that MC3T3-E1 cells rapidly adhere to NBM, reaching a peak 3 h after
      seeding. Attached cells display characteristic signs of spreading. Five to ten
      percent of total radioactivity remained on NBM after the removal of nonadherent
      cells. Viability is maintained at room temperature and under rotation for upto 3
      h. This data suggests that the dynamic in vitro model presented here provides a
      tool to study cell adhesion on granular biomaterials.

PMID- 19582841
TI  - Histomorphologic analysis of 30 plateau root form implants retrieved after 8 to
      13 years in function. A human retrieval study.
AB  - The objective of this study was to evaluate the morphology and integration status
      of 30 human retrieved plateau root form implants. Thirty plateau design root form
      implants that were in function from 8 to 13 years were retrieved from patients
      due to prosthetic reasons. Following surgical removal, the samples remained in
      10% buffered formaline for 7 days. Bone morphology was evaluated by transmitted
      and polarized light microscopy, and bone-to-implant contact (BIC)
      histomorphometric assessment was determined through computer software.
      Irrespective of time in vivo, lamellar bone was observed in close contact with
      the implant surface and between plateaus. BIC ranged from approximately 20 to
      approximately 80%. Polarized light microscopy showed a highly directional
      osteonic morphology between plateaus for most implants. A haversian-like
      microstructure running perpendicular to and along with the implants' long axis
      (between plateaus) was observed in regions of cortical and trabecular bone,
      revealing a unique bone microstructural evolution over time around functionally
      loaded plateau root form implants.

PMID- 19582842
TI  - In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces
      functionalized with BMP-2.
AB  - Poor implant fixation and bone resorption are two of the major challenges in
      modern orthopedics and are caused by poor bone/implant integration. In this work,
      bioactive crystalline titanium dioxide (TiO(2))/hydroxyapatite (HA) surfaces,
      functionalized with bone morphogenetic protein 2 (BMP-2), were evaluated as
      potential implant coatings for improved osseointegration. The outer layer
      consisted of HA, which is known to be osteoconductive, and may promote improved
      initial bone attachment when functionalized with active molecules such as BMP-2
      in a soaking process. The inner layer of crystalline TiO(2) is bioactive and
      ensures long-term fixation of the implant, once the hydroxyapatite has been
      resorbed. The in vitro response of mesenchymal stem cells on bioactive
      crystalline TiO(2)/HA surfaces functionalized with BMP-2 was examined and
      compared with the cell behavior on nonfunctionalized HA layers, crystalline
      TiO(2) surfaces, and native titanium oxide surfaces. The crystalline TiO(2) and
      the HA surfaces showed to be more favorable than the native titanium oxide
      surface in terms of cell viability and cell morphology as well as initial cell
      differentiation. Furthermore, cell differentiation on BMP-2-functionalized HA
      surfaces was found to be significantly higher than on the other surfaces
      indicating that the simple soaking process can be used for incorporating active
      molecules, promoting fast bone osseointegration to HA layers.

PMID- 19582844
TI  - Inactivation of bacterial spores and viruses in biological material using
      supercritical carbon dioxide with sterilant.
AB  - The purpose of this study was to validate supercritical carbon dioxide (SC-CO(2))
      as a terminal sterilization method for biological materials, specifically
      acellular dermal matrix. In this study, bacterial spores, Bacillus atrophaeus,
      were inoculated onto porcine acellular dermal matrix to serve as a "worst case"
      challenge device. The inactivation of the spores by SC-CO(2) with peracetic acid
      (PAA) sterilant was analyzed as a function of exposure times ranging from 1 to 30
      min. A linear inactivation profile for the Bacillus atrophaeus spores was
      observed, and a SC-CO(2) exposure time of 27 min was determined to achieve a
      sterility assurance level of 10(-6). The inactivation of viruses was also studied
      using Encephalomyocarditis (EMC) viruses. After 15 min of exposure to SC-CO(2)
      with PAA sterilant, more than a 6 log(10) reduction was observed for EMC viruses.
      Biochemical and biomechanical evaluations showed that the SC-CO(2) treatment with
      PAA sterilant did not cause significant changes in porcine acellular matrix's
      susceptibility to collagenase digestion, tensile or tear strength, indicating
      limited alteration of the tissue structure following SC-CO(2) sterilization.

PMID- 19582843
TI  - Enzyme-catalyzed hydrolysis of dentin adhesives containing a new urethane-based
      trimethacrylate monomer.
AB  - A new trimethacrylate monomer with urethane-linked groups, 1,1,1-tri-[4
      (methacryloxyethylamino-carbonyloxy)-phenyl]ethane (MPE), was synthesized,
      characterized, and used as a comonomer in dentin adhesives. Dentin adhesives
      containing 2-hydroxyethyl methacrylate (HEMA, 45% w/w) and 2,2-bis[4(2-hydroxy-3
      methacryloyloxy-propyloxy)-phenyl] propane (BisGMA, 30% w/w) in addition to MPE
      (25% w/w) were formulated with H(2)O at 0 (MPE0), 8 (MPE8), and 16 wt % water
      (MPE16) to simulate the wet demineralized dentin matrix and compared with
      controls [HEMA /BisGMA, 45/55 w/w, at 0 (C0), 8 (C8), and 16 wt % water (C16)].
      The new adhesive showed a degree of double bond conversion and mechanical
      properties comparable with control, with good penetration into the dentin surface
      and a uniform adhesive/dentin interface. On exposure to porcine liver esterase,
      the net cumulative methacrylic acid (MAA) released from the new adhesives was
      dramatically (p < 0.05) decreased relative to the control, suggesting that the
      new monomer improves esterase resistance.

PMID- 19582845
TI  - Mold fabrication and biological assessment of porous DNA-chitosan complexes.
AB  - A previous study revealed that DNA-chitosan complex prepared from the reaction
      between native DNA and chitosan in aqueous solution has suitable porosity for
      cell seeding, is nontoxic, and causes only a mild soft-tissue response. This
      simple and easy fabrication method for porous DNA-chitosan complex provides for a
      wide variety of applications as a scaffold material. The present study evaluated
      whether rinsing with PBS solution can fabricate DNA-chitosan complex in a mold
      and the histopathological responses of rat soft tissues to fabricated DNA
      chitosan complexes. DNA-chitosan complex paste was prepared by mixing distilled
      water and freeze-dried water-rinsed DNA-chitosan complex powder. A DNA-chitosan
      complex disk could be fabricated by rinsing with PBS buffer and subsequently
      freeze-drying the DNA-chitosan complex paste in the mold. Thus, a wide range of
      applications of DNA-chitosan complex for tissue engineering can be anticipated
      using the present easy fabrication method. The porosity of the disk was 85%, and
      many pores were visible in the DNA-chitosan complex (before fabrication) and in
      the fabricated DNA-chitosan disk. The values of the complex disks gradually
      reduced in the tissues although 60% of disks remained in the tissues. In
      conclusion, an easy fabrication method for making porous DNA-chitosan complex
      disks was developed. It was found that the fabrication method can delay the
      biodegradation of the DNA-chitosan complex disk without serious tissue responses
      in vivo. DNA-chitosan complex is promising as a scaffold material, and a wide
      range of applications of DNA-chitosan complex for tissue engineering are
      anticipated.

PMID- 19582846
TI  - Biodegradable inflatable balloon for reducing radiation adverse effects in
      prostate cancer.
AB  - Carcinoma of the prostate is one of the most abundant killers for men in the
      western world, and it is frequently treated via Radiation therapy. Unfortunately,
      radiotherapy side effects include rectal irritation and bleeding, erectile
      dysfunction and urinary frequency. Because radiation intensity decays rapidly as
      a function of distance, displacing irradiated prostate away from normal tissues
      would reduce damage and therefore side effects. The objective of this study is to
      develop an inflatable balloon that is implanted via a minimal invasive procedure.
      The balloon is made of a biodegradable polymer called poly(lactide-co-epsilon
      caprolactone). The implant is inserted rolled throughout the perineum; inflated
      in situ with a physiological saline; sealed and placed between the rectum wall,
      and the prostate gland. Balloon's mechanical and chemical properties were
      extensively characterized both in vitro and in vivo. The balloon's preparation
      ensures no bonding across surfaces as these may endanger the implant mechanical
      stability. Moreover, the coating method does not alter the polymer's molecular
      weight and therefore preserve its mechanical properties. Balloon's sterilization
      was carried out using ethylene oxide which, as our results show and in comparison
      with gamma-irradiation, doesn't damage the mechanical stability of the implant.
      The proper functionality of the insertion-mounting device as well as the balloon
      capability to retain its inflated form during patients' radiation session was
      demonstrated both in vitro and in vivo.

PMID- 19582847
TI  - Prolonged antibiotic delivery from anodized nanotubular titanium using a co
      precipitation drug loading method.
AB  - Advances in nanotechnology have led to the development of novel orthopedic
      implant materials that not only have better cytocompatibility properties but can
      also be used as unique drug delivery platforms. In the present study, currently
      used titanium was anodized to possess nanotubular surface structures (80 nm inner
      diameter and 200 nm deep) capable of drug delivery. Such anodized nanotubular
      titanium surfaces promote bone cell functions (such as adhesion and
      differentiation) in vitro and in vivo compared with unanodized titanium. To
      achieve local drug delivery, anodized titanium with nanotubular structures were
      loaded with penicillin-based antibiotics using a co-precipitation method in which
      drug molecules were mixed in simulated body fluid to collectively precipitate
      with calcium phosphate crystals. Results showed for the first time that such co
      precipitated coatings on anodized nanotubular titanium could release drug
      molecules for up to 3 weeks whereas previous studies have demonstrated only a 150
      minute release of antibiotics through simple physical adsorption. Furthermore,
      drug release using co-precipitation from anodized nanotubular titanium was
      determined to be a diffusion process dependent on first-order kinetics. In
      addition, contrary to conventional thinking that penicillin-based drug release
      should decrease cell functions (including both bacteria and mammalian cells),
      results of this study showed similar osteoblast (bone-forming cell) adhesion
      between non-drug loaded and drug loaded precipitated calcium phosphate coatings
      on anodized titanium. Due to the above, these findings represent a promising
      surface treatment for titanium that could be used for local drug delivery for
      improving orthopedic applications and, thus, should be studied further.

PMID- 19582849
TI  - Preparation of a completely autologous trileaflet valve-shaped construct by in
      body tissue architecture technology.
AB  - The aim of this study was to prepare completely autologous heart-valve-shaped
      constructs without using any artificial scaffold materials by in-body tissue
      architecture technology, which is a practical concept of regenerative medicine
      based on the biological defense mechanism against foreign bodies. Silicone rods
      were used as molds to achieve the tubular shape of the arteries, which were
      implanted in the subcutaneous spaces of rabbits. After 2 weeks of primary in-body
      tissue incubation, the silicone rods were completely encapsulated within a thin
      membranous connective tissue mainly consisting of collagen and having a thickness
      of approximately 100 microm. To achieve the trileaflet shape of the valve, the
      cylindrical tissues obtained were rolled up with polyurethane belts cut in the
      shape of three semi-ovals. The assembled tissues were reimplanted for 2 weeks for
      secondary incubation. The resulting tissues were over-encapsulated with the newly
      developed membranous connective tissue having a thickness of approximately 200
      400 microm. The newly formed membranes were completely fused to the previously
      developed inner membrane. After the removal of the two artificial materials,
      tubular constructs with trileaflet-shaped internal surface were obtained. By
      controlling the formation of the encapsulating tissue in the two-step in-body
      tissue incubation process, we were able to develop completely autologous
      trileaflet valve-shaped constructs.

PMID- 19582848
TI  - High molecular weight blood group A trisaccharide-polyacrylamide glycoconjugates
      as synthetic blood group A antigens for anti-A antibody removal devices.
AB  - Specific immunoadsorption of blood group antibodies by synthetic antigens
      immobilized on support matrices in the peri-transplantation period provides a
      promising solution to hyperacute rejection risk following ABO-incompatible
      transplantation. In this study, we investigated binding interactions between anti
      A antibodies and synthetic blood group A trisaccharide conjugated with
      polyacrylamide of different molecular weights (30 and 1000 kDa). The
      glycopolymers were equipped with biotin tags and deposited on streptavidin-coated
      sensor chips. The affinity and kinetics of anti-A antibodies binding to
      glycoconjugates were studied using surface plasmon resonance (SPR). The high
      molecular weight conjugate (Atri-PAA(1000)-biotin) enhanced antibody binding
      capacity by two to three fold compared with the low molecular weight conjugate
      (Atri-PAA(30)-biotin), whereas varying the carbohydrate content in Atri-PAA(1000)
      biotin (20 mol % or 50 mol %) did not affect antibody binding capacity of the
      glycoconjugate. The obtained results suggest that immunoadsorption devices,
      especially hollow fiber-based antibody filters which are limited in available
      surface area for antigen immobilization, may greatly benefit from the new
      synthetic high molecular weight polyacrylamide glycoconjugates.

PMID- 19582850
TI  - What is a "normal" wear pattern for metal-on-metal hip bearings?
AB  - In addition to classical run-in and steady-state wear phases, metal-on-metal
      (MOM) hip bearings have encountered "runaway wear" (RAW) trends in simulator
      studies. This puzzling behavior has resulted in 2- to 19-fold wear increases
      compared with other apparently "identical" bearings. MOM bearings have shown five
      identifiable RAW wear patterns in joint simulators; therefore, additional
      descriptive terms were used here to indicate various observed patterns, for
      example, "breakaway wear" (BAW), which was defined as a higher wear trend that
      recovers to steady-state wear. As these trends commonly occur for MOM, this
      raises the question of what can be considered "normal" behavior or "abnormal"? In
      an effort to identify possible causes for this behavior, the current study
      investigated six Co-Cr bearings, which closely matched with respect to
      geometrical tolerances. Despite close control of design and test variables, BAW
      occurred in 30% of the MOM bearings, producing a threefold wear increase above
      otherwise identical MOM bearings within the same group. The majority of the BAW
      (85%) occurred on the cup side and was validated by growth of wear scars and
      concentrations of metal ions. One bearing that showed continuing BAW at 5 Mc
      revealed a cup that was 50% smoother than other cups whereas its mating head was
      50% rougher, thus signifying that highly polished areas were sites of the highest
      MOM wear. The two BAW bearings with high wear showed the greatest conformity at 5
      Mc, in apparent contradistinction to classical lubrication theory.

PMID- 19582851
TI  - Drug-eluting stent with improved durability and controllability properties,
      obtained via electrocoated adhesive promotion layer.
AB  - Drug-eluting stents (DES) have become an accepted technology in intravascular
      intervention. Manufacturing methodologies of DES are based mainly on mechanical
      processes, which tend to generate coatings that have poor stability properties;
      these were recently related as a potential hazard. A novel approach for
      significantly increasing the adhesion of polymer coatings onto DES is presented.
      The method is based on the electrochemistry of diazonium salts. These substances
      are organic compounds with the characteristic structure of R-N(2) (+) X(-), where
      R is an organic residue and X(-) is an anion. The objective of this article is to
      study the properties of a selected diazonium salt 4-(1-dodecyloxy)
      phenyldiazonium tetrafluoroborate, referred as C(12)-phenyldiazonium. This
      material was found to be a superior adhesive promoter for polymeric coatings
      applied onto metallic stents. C(12)-phenyldiazonium was synthesized and
      electrocoated on metallic stents and plates. The multilayer films of C(12)
      phenyldiazonium were further characterized through electrochemical (cyclic
      voltammetry, impedance spectroscopy), physical (light and scanning electron
      microscopy, X-ray photoelectron spectroscopy, peeling tests), and chemical
      methodology (high pressure liquid chromatography). Further biocompatibility
      properties of the electrocoated basecoat were evaluated using in vitro and in
      vivo models. Synthesized C(12)-phenyldiazonium was successfully electrocoated
      onto metallic surfaces. Electrochemical tests demonstrated its efficient and
      controllable electrocoating. C(12)-phenyldiazonium was found to increase
      polymeric coating stability as was reflected by a standard adhesion test.
      Electrocoated metallic stents spray-coated with a second polymeric film showed
      improved durability following incubation in physiological buffer. Furthermore,
      this improvement in durability exhibits stabilized drug release. In addition,
      biocompatibility evaluations have demonstrated basecoat's inert properties.

PMID- 19582852
TI  - A loading device suitable for studying mechanical response of bone cells in hard
      scaffolds.
AB  - Bone cells live in an environment heavily influenced by mechanical forces.
      Systematic study of cell's mechanical responses has relied greatly on the in
      vitro experiments due to complexity of internal environment of bone cells in
      vivo. A loading device suitable to hard scaffolds for studying mechanical
      responses of bone cells was made by using a kind of long-travel, high-load
      piezoelectric actuator. The device, which was precisely controlled by computer,
      and designed to work in an incubator at 37 degrees C and 100% humidity, can cause
      hard scaffolds with directly compressive strains with more magnitudes, frequency
      components, and waveforms, including bone physiologically mechanical state. The
      experiment using hard scaffolds indicates the device validity. The device
      represents a versatile model that will provide conditions for investigating the
      effects of mechanical responses on bone cells in 3D hard scaffolds in vitro. In
      addition, the preliminary biological test was performed by the application of the
      device. The results showed that the dynamic compression with the amplitude of
      1000 microstrain, the frequency of 3 Hz, the duration of 3 min/day enhanced the
      osteoblastic proliferation and extracellular matrix compared with static
      conditions, and improved the cell distribution within scaffolds. The researches
      of 3D mechanical effects on bone cells just in hard scaffolds similar to that in
      cancellous bone can enhance the understanding of bone physiology in vivo. The
      direct, dynamic contact-loading of the device may provide an appropriate
      mechanical condition in bone tissue engineering culture.

PMID- 19582854
TI  - Preparation and characterization of calcium sulfate-biomimetic apatite
      nanocomposites for controlled release of antibiotics.
AB  - In the present study, release properties of antibiotic-loaded cement-type
      nanocomposites of biomimetic apatite and calcium sulfate were studied.
      Nanocrystalline component of the nanocomposite was synthesized by soaking a
      mixture of calcium phosphate reactants in tris-buffered simulated body fluid
      (SBF). The release patterns of cephalexin and gentamicin from both pure calcium
      sulfate and nanocomposite cements into SBF were collected up to 144 h and fitted
      by Higuchi and Weibull equations. The effect of loaded antibiotics on physical
      properties of the cements was also evaluated. Fast release behavior of both
      antibiotics was obtained from calcium sulfate matrix, in which 80-85% of the
      loaded antibiotics were liberated during the first 10 h of elution. In contrast,
      an administered elution was acquired from nanonocomposite materials so that the
      release was controlled, in all cases, by a combined mechanism; major mechanism
      was drug diffusion through the matrix and the minor was matrix dissolution. The
      results showed that the initial setting time and injectability of cements were
      increased from 7 min and 71% for pure calcium sulfate cement (powder-to-liquid
      ratio = 2.5 g/mL) to 33 min and 95% for the nanocomposite cement containing 60 wt
      % apatite, respectively. The compressive strength of nanocomposite was about 0.9
      MPa, nearly four times lower than that of pure calcium sulfate. In addition, the
      use of cephalexin monohydrate did not influence the setting time and compressive
      strength of the cements, whereas (adding) gentamicin sulfate significantly
      improved these properties.

PMID- 19582853
TI  - Evaluation of encapsulated Newcastle disease virus liposomes using various
      phospholipids administered to improve chicken humoral immunity.
AB  - We propose the adjuvant effects of phospholipid liposome compositions using
      intranasal inoculation of a liposomal-Newcastle disease virus (NDV) vaccine in
      chickens. The immunogenicity of three liposome formulations was determined in
      chickens using the hemagglutination-inhibition (HI) test, nasal secretory
      immunoglobulin A and serum immunoglobulin A (IgG) antibody titers using the
      enzyme-linked immunosorbent assay. The immune response against NDV antigens was
      determined after immunization with neutral charged liposomes composed of egg
      phosphatidylcholine (EPC) (60 micromol), cholesterol (Chol) (15 micromol), and
      EPC-liposomes (EPC-Lip), which elicited strong systemic (serum) and local (nasal)
      humoral responses. However, the intranasal administration with cationic charged
      liposomes composed of EPC (30 micromol), stearylamine (SA) (15 micromol), Chol
      (15 micromol), and SA-liposomes (SA-Lip) induced poor humoral immune responses.
      Only the vaccine formulated with anionic charged liposomes composed of EPC (30
      micromol), dipalmitoylphosphatidylserine (15 micromol), Chol (15 micromol), and
      phosphatidylserine-liposomes (PS-Lip) elicited the highest titers of HI
      antibodies. These are the first results to suggest that antigen delivery using
      EPC-Lip is very useful in enhancing antibody production at the mucosal site and
      in serum.

PMID- 19582856
TI  - Experimental immediate loading of dental implants in conjunction with grafting
      procedures.
AB  - The aim of this study was to evaluate immediate loading (IL) of dental implants
      in conjunction with grafting procedures. A total of 107 IL implants were inserted
      in six mini pigs. Before implant placement, crestal or apical defects were
      created, which were treated with bone chips, phycogene hydroxyapatite (HA),
      bovine HA, or bovine HA enhanced with a synthetic peptide. Crestal grafts were
      stabilized with titanium membranes. All bridges were in function and showed signs
      of chewing wear after 4-month loading. Three out of 107 implants showed no
      osseointegration (2.7%). Most of the crestal defects showed incomplete
      regeneration, due to an infection of the membranes (74.3%) The difference in
      height between surgical and remaining defect was calculated as defect
      development, which was 2.3 +/- 2.08 mm for bone chips with an area of regenerated
      bone of 22.8 +/- 3.34% and 0.7 +/- 2.22 mm for phycogene HA with 11.3 +/- 4.36%
      regenerated bone. Bovine HA showed an increase of defects 1.3 +/- 2.47 mm with
      only 7.9 +/- 1.7% bone regeneration. Bovine HA enhanced with a peptide showed a
      defect development of 1.1 +/- 1.42 mm with an area of regenerated bone of 18.2 +/
      2.38%. In conclusion, local grafting procedures did not disturb the course of
      osseointegration for immediate loaded implants if primary stability was reached.
      The regeneration of apical defects was uneventful even with immediate loading.
      Crestal defects required membrane fixation with a careful flap elevation to avoid
      membrane exposure and loss of the graft.

PMID- 19582855
TI  - Comparison of the response of cultured osteoblasts and osteoblasts outgrown from
      rat calvarial bone chips to nonfouling KRSR and FHRRIKA-peptide modified rough
      titanium surfaces.
AB  - Mimicking proteins found in the extracellular matrix (ECM) using specific peptide
      sequences is a well-known strategy for the design of biomimetic surfaces, but has
      not yet been widely exploited in the field of biomedical implants. This study
      investigated osteoblast and, as a control, fibroblast proliferation to novel
      consensus heparin-binding peptides sequences KRSR and FHRIKKA that were
      immobilized onto rough (particle-blasted and chemically etched) commercially pure
      titanium surfaces using a poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG)
      molecular assembly system. This platform enabled a detailed study of specific
      cell-peptide interactions even in the presence of serum in the culture medium;
      thanks to the excellent nonfouling properties of the PLL-g-PEG surface. Cell
      binding peptide sequence RGD in combination with KRSR or FHRRIKA was used to
      examine a potentially-enhanced or synergistic effect on osteoblast proliferation.
      Bare titanium and bioinactive surfaces (i.e., unfunctionalized PLL-g-PEG and
      scrambled KSSR, RFHARIK, and RDG) were used as control substrates. Additionally,
      in a newly developed experimental setup, freshly harvested bone chips from
      newborn rat calvariae were placed onto the same type of surfaces investigating
      size and pattern of osteoblast outgrowths. The findings of the current study
      demonstrated that the difference in osteoblast and fibroblast proliferation was
      influenced by surface topography more so than by the presence of surface-bound
      KRSR and FHRRIKA. On the other hand, in comparison with the control surfaces,
      osteoblast outgrowths from rat calvarial bone chips covered a significantly
      larger area on RGD, KRSR, and FHRRIKA surfaces after 8 days and also migrated in
      an isotropic way unlike cells on the bioinactive substrates. Furthermore, the
      stimulatory effect of 0.75 pmol cm(-2) RGD on osteoblast migration pattern could
      be enhanced when applied in combination with 2.25 pmol cm(-2) KRSR.

PMID- 19582857
TI  - ATR-FTIR as a thickness measurement technique for hydrated polymer-on-polymer
      coatings.
AB  - Hydrated polymer coatings on polymer substrates are common for many biomedical
      applications, such as tissue engineering constructs, contact lenses, and
      catheters. The thickness of the coatings can affect the mechanical behavior of
      the systems and the cellular response, but measuring the coating thickness can be
      quite challenging using conventional methods. We propose a new method, that is,
      attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) to
      determine the relative thickness, combined with atomic force microscopy to
      calibrate the ATR-FTIR measurements. This technique was successfully employed to
      determine the hydrated thickness of a series of crosslinked tetraglyme coatings
      on ultrahigh molecular weight polyethylene substrates intended to reduce wear of
      acetabular cups in total hip replacements. The hydrated coatings ranged from 30
      to 200 nm thick and were accurately measured despite the relatively high root
      mean-square (RMS) roughness of the substrates, 20-35 nm (peak-to-peak roughness
      55-100 nm). The calibrated ATR-FTIR technique is a promising new method for
      measuring the thickness of many other polymer-on-polymer and hydrated coatings.

PMID- 19582858
TI  - Adsorption and release of BMP-2 on nanocrystalline apatite-coated and uncoated
      hydroxyapatite/beta-tricalcium phosphate porous ceramics.
AB  - The association of bone morphogenetic proteins (BMPs) with calcium phosphate
      bioceramics is known to confer them osteoinductive properties. The aim of this
      study was to evaluate the surface properties, especially regarding recombinant
      human BMP-2 (rhBMP-2) adsorption and release, of commercial sintered biphasic
      calcium phosphate ceramics after coating with biomimetic nanocrystalline apatite.
      The raw and coated ceramics exhibited similar macroporous structures but
      different nanometer-sized pores contents. Both types of ceramics showed Langmuir
      type adsorption isotherms of rhBMP-2. The coating noticeably increased the rate
      of adsorption and the total amount of growth factor taken up, but the maximum
      coverage per surface area unit as well as the affinity constant appeared lower
      for coated ceramics compared with raw ceramic surfaces. The limited advantage
      gained by coating the ceramics can be assigned to a lower accessibility of the
      surface adsorption sites compared with the raw ceramics. The quantity of rhBMP-2
      spontaneously released in cell culture medium during the first weeks was lower
      for coated samples than for uncoated ceramics and represented a minor fraction of
      the total adsorbed amount. In conclusion, the nanocrystalline apatite coating was
      found to favor the adsorption of rhBMP-2 while providing a mean to fine tune the
      release of the growth factor.

PMID- 19582859
TI  - Porosity and semipermeability of hemoglobin-loaded polymeric nanoparticles as
      potential blood substitutes.
AB  - Porosity and semipermeability, allowing life-sustaining small molecules to
      penetrate, but hemoglobin (Hb) and other enzymes to cut off, predominantly affect
      the functionalities of the Hb-loaded polymeric nanoparticles (HbPNPs) as blood
      substitutes. In this article, HbPNPs formulated in the size range of 110-122 nm
      were prepared by a modified double-emulsion method with poly(lactic acid) (PLA)
      based polymers. The influences of the main preparation conditions, including
      solvent composition, stirring speed, Hb concentration and polymer matrix, on the
      porosity were investigated in details. To evaluate the porosity of HbPNPs, a
      novel nondestructive testing method based on molecular weight cut-off (MWCO) was
      developed, and an effusion approach was applied to investigate the pore size in
      the particle shells with poly(ethylene glycol)s (PEGs) of different molecular
      weights (PEG200, PEG400, PEG600) as probes. Moreover, in vitro diffusion
      behaviors of ascorbic acid and reduced glutathione from HbPNPs fabricated with
      various polymer matrices were studied. The MWCO of HbPNPs by changing solvent
      composition, stirring speed, Hb concentration, and polymer composition varied
      from 200 to 600, especially the PEGylation of the polymer, which exhibited
      obvious influence on the MWCO of HbPNPs. Ascorbic acid with molecular weight
      176.1 could diffuse into PEGylated nanoparticles with mPEG content of 5-30 wt %
      freely, while reduced glutathione with molecular weight 307.3 could not penetrate
      when mPEG content reached 30 wt %. These results suggest that the HbPNPs
      optimized with MWCO between 400 and 600 can facilitate the transport of all those
      life-sustaining small molecules.

PMID- 19582860
TI  - Nonlinear visco-elastic finite element analysis of different porcelain veneers
      configuration.
AB  - This study is aimed at evaluating the biomechanical behavior of feldspathic
      versus alumina porcelain veneers. A 3D numerical model of a maxillary central
      incisor, with the periodontal ligament (PDL) and the alveolar bone was generated.
      Such model was made up of four main volumes: dentin, enamel, cement layer and
      veneer. Incisors restored with alumina and feldspathic porcelain veneers were
      compared with a natural sound tooth (control). Enamel, cementum, cancellous and
      cortical bone were considered as isotropic elastic materials; on the contrary,
      the tubular structure of dentin was designed as elastic orthotropic. The
      nonlinear visco-elatic behavior of the PDL was considered. The veneer volumes
      were coupled with alumina and feldspathic porcelain mechanical properties. The
      adhesive layers were modeled in the FE environment using spring elements. A 50N
      load applied at 60 degrees angle with tooth longitudinal axis was applied and
      validated. Compressive stresses were concentrated on the external surface of the
      buccal side of the veneer close to the incisal margin; such phenomenon was more
      evident in the presence of alumina. Tensile stresses were negligible when
      compared to compressive ones. Alumina and feldspathic ceramic were characterized
      by a different biomechanical behavior in terms of elastic deformations and stress
      distributions. The ultimate strength of both materials was not overcome in the
      performed analysis.

PMID- 19582861
TI  - Measurement errors related to contact angle analysis of hydrogel and silicone
      hydrogel contact lenses.
AB  - This work sought to undertake a comprehensive investigation of the measurement
      errors associated with contact angle assessment of curved hydrogel contact lens
      surfaces. The contact angle coefficient of repeatability (COR) associated with
      three measurement conditions (image analysis COR, intralens COR, and interlens
      COR) was determined by measuring the contact angles (using both sessile drop and
      captive bubble methods) for three silicone hydrogel lenses (senofilcon A,
      balafilcon A, lotrafilcon A) and one conventional hydrogel lens (etafilcon A).
      Image analysis COR values were about 2 degrees , whereas intralens COR values
      (95% confidence intervals) ranged from 4.0 degrees (3.3 degrees , 4.7 degrees )
      (lotrafilcon A, captive bubble) to 10.2 degrees (8.4 degrees , 12.1 degrees )
      (senofilcon A, sessile drop). Interlens COR values ranged from 4.5 degrees (3.7
      degrees , 5.2 degrees ) (lotrafilcon A, captive bubble) to 16.5 degrees (13.6
      degrees , 19.4 degrees ) (senofilcon A, sessile drop). Measurement error
      associated with image analysis was shown to be small as an absolute measure,
      although proportionally more significant for lenses with low contact angle.
      Sessile drop contact angles were typically less repeatable than captive bubble
      contact angles. For sessile drop measures, repeatability was poorer with the
      silicone hydrogel lenses when compared with the conventional hydrogel lens; this
      phenomenon was not observed for the captive bubble method, suggesting that
      methodological factors related to the sessile drop technique (such as surface
      dehydration and blotting) may play a role in the increased variability of contact
      angle measurements observed with silicone hydrogel contact lenses.

PMID- 19582862
TI  - A comparison of experimental aneurysm occlusion determination by angiography,
      scanning electron microscopy, MICROFIL perfusion, and histology.
AB  - In clinical practice, occlusion of embolized, intracerebral aneurysms is
      evaluated using angiography. Standard, two-dimensional digital subtract
      angiography (DSA) is unable to quantify irregular aneurysm remnants, and even
      three-dimensional rotational angiography cannot quantify the degree of occlusion.
      To better understand occlusion at the aneurysm neck, we compared angiographic
      results with MICROFIL perfusion, histology, and scanning electron microscopy
      (SEM) results in 20 elastase-induced saccular aneurysms in rabbits. Aneurysms
      were embolized with HydroCoil devices (n = 12) or platinum coils (n = 8).
      Aneurysm follow-up occurred at 2 (n = 10) and 6 (n = 10) weeks. Aneurysm
      occlusion was evaluated using DSA, MICROFIL perfusion, histological ground
      sections, and SEM. Groups were compared statistically using ANOVA and chi(2)
      tests. The MICROFIL perfusion results were not concordant with the angiographic
      results for the HydroCoil and platinum coil groups. Both increased and decreased
      occlusion was observed on the MICROFIL-perfused aneurysms when compared with
      angiography. The histologic occlusion results of the HydroCoil group were
      concordant with the angiographic results; however, unoccluded areas not visible
      on angiography were routinely observed on the ground sections in the platinum
      coil group. SEM imaging of the aneurysm neck consistently showed decreased
      occlusion than angiographic results for both the HydroCoil and platinum coil
      groups. Although histology and MICROFIL-perfusion analyses provided additional
      details of aneurysm occlusion when compared with angiography, complete
      visualization of the entire neck of the aneurysm and accurate assessment of
      aneurysm occlusion was possible only with SEM.

PMID- 19582863
TI  - Evaluation of the efficacy of platelet-rich plasma in delivering BMSCs into 3D
      porous scaffolds.
AB  - Platelet-rich plasma (PRP), derived from autologous whole blood, is rich in
      fibrinogen and platelets, which release multiple active factors in response to
      thrombin. The purpose of this study was to evaluate the efficacy of PRP in
      delivering bone marrow stromal cells (BMSCs) into 3D porous scaffolds in
      comparison with platelet-poor plasma (PPP) and Dulbecco's modified Eagle's medium
      (DMEM). The seeding efficacy, proliferation, and differentiation of the BMSCs
      seeded into poly(lactic-co-glycolic acid) (PLGA) porous scaffolds via PRP, PPP,
      and DMEM were tested. Additionally, BMSC/PLGA constructs were implanted in goat
      calvarial defects to radiologically and histologically detect the capability of
      PRP for enhancing bone regeneration. The results showed that the BMSC seeding
      efficacy of PRP was similar as that of PPP, and greater potential for in vitro
      BMSC proliferation and in vivo bone regeneration than PPP and DMEM. Therefore,
      PRP can potentially accomplish convenient and effective cell delivery into porous
      scaffolds, which is valuable in bone tissue engineering.

PMID- 19582865
TI  - The flow cytometry shared resource laboratory: best practices to assure a high
      quality, cost-effective partnership with biomedical research laboratories.

PMID- 19582864
TI  - What drives cell morphogenesis: a look inside the vertebrate photoreceptor.
AB  - Vision mediating photoreceptor cells are specialized light-sensitive neurons in
      the outer layer of the vertebrate retina. The human retina contains approximately
      130 million of such photoreceptors, which enable images of the external
      environment to be captured at high resolution and high sensitivity. Rod and cone
      photoreceptor subtypes are further specialized for sensing light in low and high
      illumination, respectively. To enable visual function, these photoreceptors have
      developed elaborate morphological domains for the detection of light (outer
      segments), for changing cell shape (inner segments), and for communication with
      neighboring retinal neurons (synaptic terminals). Furthermore, rod and cone
      subtypes feature unique morphological variations of these specialized
      characteristics. Here, we review the major aspects of vertebrate photoreceptor
      morphology and key genetic mechanisms that drive their formation. These
      mechanisms are necessary for cell differentiation as well as function. Their
      defects lead to cell death.

PMID- 19582868
TI  - Xenopus Wnt11b is identified as a potential pronephric inducer.
AB  - In this study, we aimed to establish if known wnt signaling molecules could be
      responsible for inducing early pronephros specification, using a novel and
      effective in vitro bioassay in Xenopus embryos. Anterior somites have the unique
      biological activity to signal to unspecified intermediate mesoderm to induce
      pronephros formation in Xenopus embryos. We have used a molecular candidate gene
      approach to analyze both canonical and noncanonical wnt expression in isolated
      anterior and posterior somites and dissected presumptive pronephros, pronephric
      anlagen, and pronephros from stage 12.5-35 embryos. We have identified potential
      candidate wnt genes expressed in the right time and place to specify pronephric
      development. These candidates were then directly tested in an in vitro
      pronephrogenesis assay based on Holtfreter sandwich cultures. Results revealed
      that noncanonical wnt11b and wnt11 can induce pronephros formation in vitro. Loss
      of-function experiments confirmed that these genes are necessary for normal
      pronephros development.

PMID- 19582867
TI  - What are infant siblings teaching us about autism in infancy?
AB  - International research to understand infant patterns of development in autism
      spectrum disorders (ASDs) has recently focused on a research paradigm involving
      prospective longitudinal studies of infant siblings of children with autism. Such
      designs use a comparison group of infant siblings without any familial risks (the
      low-risk group) to gather longitudinal information about developmental skills
      across the first 3 years of life, followed by clinical diagnosis of ASD at 36
      months. This review focuses on five topics: presence of ASD in the infant sibling
      groups, patterns and characteristics of motor development, patterns and
      characteristics of social and emotional development, patterns and characteristics
      of intentional communication, both verbal and nonverbal, and patterns that mark
      the onset of behaviors pathognomonic for ASD. Symptoms in all these areas
      typically begin to be detected during the age period of 12-24 months in infants
      who will develop autism. Onset of the symptoms occurs at varying ages and in
      varying patterns, but the pattern of frank loss of skills and marked regression
      reported from previous retrospective studies in 20-30% of children is seldom
      reported in these infant sibling prospective studies. Two surprises involve the
      very early onset of repetitive and unusual sensory behaviors, and the lack of
      predictive symptoms at the age of 6 months. Contrary to current views that autism
      is a disorder that profoundly affects social development from the earliest months
      of life, the data from these studies presents a picture of autism as a disorder
      involving symptoms across multiple domains with a gradual onset that changes both
      ongoing developmental rate and established behavioral patterns across the first 2
      3 years of life.

PMID- 19582869
TI  - Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and
      inner ear malformation in mice.
AB  - Smad4 is the central intracellular mediator of transforming growth factor-beta
      (TGF-beta) signaling, which plays crucial roles in tissue regeneration, cell
      differentiation, embryonic development, and regulation of the immune system.
      Conventional Smad4 gene knockout results in embryonic lethality, precluding its
      use in studies of the role of Smad4 in inner ear development. We used chondrocyte
      specific Smad4 knockout mice (Smad4Co/Co) to investigate the function of Smad4 in
      inner ear development. Smad4Co/Co mice were characterized by a smaller cochlear
      volume, bone malformation, and abnormalities of the osseous spiral lamina and
      basilar membrane. The development of the hair cells was also abnormal, as
      evidenced by the disorganized stereocilia and reduced density of the neuronal
      processes beneath the hair cells. Auditory function tests revealed the homozygous
      Smad4Co/Co mice suffered from severe sensorineural hearing loss. Our results
      suggest that Smad4 is required for inner ear development and normal auditory
      function in mammals.

PMID- 19582872
TI  - Scalable analysis of flow cytometry data using R/Bioconductor.
AB  - Flow cytometry is one of the fundamental research tools available to the life
      scientist. The ability to observe multidimensional changes in protein expression
      and activity at single-cell resolution for a large number of cells provides a
      unique perspective on the behavior of cell populations. However, the analysis of
      complex multidimensional data is one of the obstacles for wider use of
      polychromatic flow cytometry. Recent enhancements to an open-source platform
      R/Bioconductor-enable the graphical and data analysis of flow cytometry data.
      Prior examples have focused on high-throughput applications. To facilitate wider
      use of this platform for flow cytometry, the analysis of a dataset, obtained
      following isolation of CD4(+)CD62L(+) T cells from Balb/c splenocytes using
      magnetic microbeads, is presented as a form of tutorial. A common workflow for
      analyzing flow cytometry data was presented using R/Bioconductor. In addition,
      density function estimation and principal component analysis are provided as
      examples of more complex analyses. The compendium presented here is intended to
      help illuminate a path for inquisitive readers to explore their own data using
      R/Bioconductor (available as Supporting Information).

PMID- 19582870
TI  - Cadherin-11 controls otolith assembly: evidence for extracellular cadherin
      activity.
AB  - Cadherin-11/Cdh11 is expressed through early development and strongly during
      inner ear development (otic placode and vesicle). Here we show that antisense
      knockdown of Cdh11 during early zebrafish development interferes with otolith
      formation. Immunofluorescence labeling showed that Cdh11 expression was
      concentrated on and within the otolith. Cdh11 was faintly detected at the lateral
      surface (sites of cell-cell contact) of otic epithelial cells and in the
      cytoplasm. Strongly labeled Cdh11 containing puncta were detected within the
      otolymph (the fluid within the otic vesicle) and associated with the otolith
      surface. BODIPY-ceramine-labeled vesicular structures detected in the otolymph
      were larger and more numerous in Cdh11 knockdown embryos. We present evidence
      supporting a working model that vesicular structures containing Cdh11 (perhaps
      containing biomineralization components) are exported from the otic epithelium
      into the otolymph, adhere to one another and to the surface of the growing
      otolith, facilitating otolith growth.

PMID- 19582871
TI  - Loss of dystrophin and the microtubule-binding protein ELP-1 causes progressive
      paralysis and death of adult C. elegans.
AB  - EMAP-like proteins (ELPs) are conserved microtubule-binding proteins that
      function during cell division and in the behavior of post-mitotic cells. In
      Caenorhabditis elegans, ELP-1 is broadly expressed in many cells and tissues
      including the touch receptor neurons and body wall muscle. Within muscle, ELP-1
      is associated with a microtubule network that is closely opposed to the integrin
      based adhesion sites called dense bodies. To examine ELP-1 function, we utilized
      an elp-1 RNA interference assay and screened for synthetic interactions with
      mutated adhesion site proteins. We reveal a synthetic lethal relationship between
      ELP-1 and the dystrophin-like protein, DYS-1. Reduction of ELP-1 in a dystrophin
      [dys-1(cx18)] mutant results in adult animals with motility defects, splayed and
      hypercontracted muscle with altered cholinergic signaling. Worms fill with
      vesicles, become flaccid, and die. We conclude that ELP-1 is a genetic modifier
      of a C. elegans model of muscular dystrophy.

PMID- 19582874
TI  - Endothelial progenitor cells do not contribute to tumor endothelium in primary
      and metastatic tumors.
AB  - Despite extensive research, the contribution of bone-marrow-derived endothelial
      progenitor cells (BM-EPC) to tumor angiogenesis remains controversial. In
      previous publications, the extent of incorporation of BM-EPCs into the
      endothelial cell (EC) layer in different tumor models has been reported as
      significant in some studies but undetectable in others. Here, we studied the
      differentiation of BM-EPCs and its contribution to tumor vessels in experimental
      and spontaneous lung metastasis (B16 melanoma and prostate carcinoma), in an
      autochthonous transgenic model of prostate tumorigenesis, in orthotopically
      implanted lung tumors [Lewis lung carcinoma (LLC)], in heterotopic subcutaneous
      models (LLC and C1 prostate carcinoma) growing in green fluorescent protein (GFP)
      expressing bone marrow (BM) chimeras. Immunofluorescence was performed with a set
      of endothelial and hematopoietic markers and confocal microscopy was used to
      generate 3D reconstruction images. By performing rigorously conducted
      morphological studies, we found no evidence of BM-EPCs differentiation into tumor
      endothelium independently of tumor type, grade and organ site in primary and
      metastatic tumors. The vast majority of GFP(+) cells were trafficking leucocytes
      or periendothelial myeloid cells. To explore the possibility that local
      overexpression of vascular endothelial growth factor (VEGF) might increase the
      numbers of incorporated BM-EPCs, we analyzed tumors genetically manipulated to
      overexpress VEGF(164). Local VEGF production induces a massive infiltration of
      bone-marrow-derived cells, but did not lead to vessel wall integration of these
      cells. Collectively, these findings suggest that during tumor progression
      vascularization occurs primarily via classical tumor angiogenesis (e.g.,
      sprouting of pre-existing ECs), whereas BM-EPCs do not incorporate into the
      vessel wall to any significant extent.

PMID- 19582873
TI  - Efficient characterization of the TCR repertoire in lymph nodes by flow
      cytometry.
AB  - Analysis of the T-cell receptor (TCR) repertoire by flow cytometry proved to be
      relevant for investigating T-cell diversity and detecting reactive cells in blood
      samples. We used this approach to characterize non-malignant T-lymphocytes in
      lymph nodes and give insights into their origin. The TCR repertoire of CD4+ and
      CD8+ T-cells from 81 lymph nodes was analyzed with a four-color flow cytometer
      using a wide panel of 25 anti-Vbeta monoclonal antibodies. Flow cytometry proved
      to be a useful and informative technique. We demonstrated a diversified TCR-Vbeta
      repertoire, and only low level expansions, in 53% of the samples. They involved
      nearly all Vbeta families, were more frequent in the CD8+ subset of older
      patients, but were not related to pathology. No evidence could be demonstrated in
      favor of stimulation by common antigens. Interestingly, the TCR-Vbeta repertoire
      proved to be very similar in lymph nodes and blood samples. Our results argue
      that in the cases studied, lymph node enlargement is mainly due to an increased
      homing of circulating T-cells. They also provide reference values for expression
      of 25 TCR-Vbeta in lymph nodes, which could serve as a basis for further
      applications in diagnosis of T-cell lymphoproliferative disorders.

PMID- 19582875
TI  - Stanniocalcin 2 promotes invasion and is associated with metastatic stages in
      neuroblastoma.
AB  - Stanniocalcin 2 (STC2) is a secreted glycoprotein of as yet unknown functions. We
      investigated STC2 in human neuroblastoma, the most common solid extra-cranial
      tumor of infancy. In primary tumor samples, we found that expression of STC2 is
      associated with the metastatic Stages 4 and 4s and MYCN expression. In vitro,
      however, we demonstrate that cell proliferation is reduced by STC2 due to an
      increase in the basal apoptosis rate of the transfected cells. On the other hand,
      in vitro assays showed that STC2-transfected neuroblastoma cells have an
      increased invasive potential and display higher activity of collagen-degrading
      matrix metalloproteinase 2 (MMP2). Using experimental tumors on the chick
      chorioallantoic membrane (CAM), we observed that STC2 expressing cells show signs
      of emigration from the solid tumor and destroy blood vessels of the CAM, giving
      rise to massively bleeding tumors. Erosion of blood vessels was also seen when
      purified STC2 protein was applied on the CAM. Taken together, we demonstrate a
      dual role for STC2 in neuroblastoma. It reduces proliferation of tumor cells in
      vitro, but increases the invasive potential and induces bleeding, and thereby may
      facilitate early metastasis. The potential of STC2 as a surrogate marker for
      metastatic neuroblastoma calls for further investigation.

PMID- 19582876
TI  - Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma.
AB  - Annexins (ANXs) are a family of calcium and phospholipid binding proteins that
      have been implicated in diverse important biological and physiological process.
      ANX A10 (ANXA10) is a member of this family, though little is known about its
      functions. In the present study, array based comparative genomic hybridization
      (CGH) was used to screen DNA copy number change in gastric cancer cell lines and
      the results obtained were compared with oligonucleotide microarray data. DNA loss
      of the ANXA10 locus in chromosome 4q33 was found in several gastric cancer cell
      lines by array based CGH and these cell lines showed decreased ANXA10 expression
      by oligonucleotide microarray analysis. Functional analysis using siRNA and full
      length cDNA transfection in gastric cancer cell lines demonstrated that ANXA10
      regulates gastric cancer cell proliferation. Of the 585 primary gastric carcinoma
      tissues examined, ANXA10 expression at the protein level was found to be reduced
      in 289 (49.4%) cases. Quantitative real-time PCR analysis validated loss of DNA
      at the ANXA10 locus in gastric carcinomas with reduced ANXA10 expression. By
      univariate survival analysis, lack of ANXA10 expression was associated with poor
      survival (p = 0.016). These results suggest that ANXA10 inactivation by
      chromosomal deletion may play a role during gastric cancer progression.

PMID- 19582877
TI  - Antibodies blocking adhesion and matrix binding domains of laminin-332 inhibit
      tumor growth and metastasis in vivo.
AB  - Laminin-332 (LN-332), which is essential for epithelial cell adhesion and
      migration, is up-regulated in most invasive carcinomas. Association between LN
      332 and carcinoma cell integrins and stroma collagen is thought to be important
      for tumor growth and metastasis. Here, we show that function blocking LN-332
      antibodies interfering with cellular adhesion and migration in vitro evoke
      apoptotic pathways. The antibodies also target epithelial tumors in vivo.
      Antibodies against the cell binding domain of the alpha3 chain of LN-332
      inhibited tumor growth by up to 68%, and antibodies against the matrix binding
      domains of the beta3 and gamma2 chains significantly decreased lung metastases.
      The LN-332 antibodies appear to induce tumor cell anoikis and subsequent
      programmed cell death and reduce migration by interfering with tumor cell matrix
      interactions.

PMID- 19582878
TI  - Upregulation of caveolin-1 and CD147 expression in nasopharyngeal carcinoma
      enhanced tumor cell migration and correlated with poor prognosis of the patients.
AB  - Expression of caveolin-1 (Cav-1) and extracellular matrix metalloproteinase
      inducer (EMMPRIN/CD147) and their prognostic significance were analyzed in
      archive NPC samples. Cav-1 and CD147 were overexpressed in 49.48% (96/194) and
      59.39% (117/197) of NPC, respectively. Both Cav-1 and CD147 expression levels
      correlated significantly with metastasis (p = 0.025 and 0.017, respectively) and
      a lower 5-year survival rate (p = 0.02 and 0.0009, respectively). In addition,
      Cav-1 expression levels correlated significantly with local recurrence (p =
      0.038). Multivariate Cox regression analysis indicated that combination of high
      Cav-1 and CD147 expression was a significant, independent prognosis predictor in
      patients with NPC (HR = 2.135; p = 0.006). Functional studies revealed that
      overexpression of Cav-1 promoted secretion of MMP-3 and MMP-11 (active) proteins,
      as well as an increase in the migratory ability of CNE1 and CNE2 cells, while
      siRNA-mediated silencing of Cav-1 or CD147 led to reduced levels of MMP-3 and MMP
      11(active) secretion, and reduced migration capacity of CNE1 and CNE2 cells. We
      observed a positive correlation between Cav-1 and CD147 expression in NPC (rho =
      0.330, p = 0.000), CD147 protein levels were upregulated in Cav-1 overexpressing
      CNE1 and CNE2 cells, whereas siRNA-mediated silencing of Cav-1 led to the
      downregulation of CD147 expression. Our results indicate that Cav-1 and CD147
      overexpression predict poor NPC prognosis and enhanced tumor cell migration,
      which is associated with MMP-3 and MMP-11 (active) secretion.

PMID- 19582880
TI  - Expression of the macrophage antigen CD163 in rectal cancer cells is associated
      with early local recurrence and reduced survival time.
AB  - Expression of the macrophage antigen CD163 in breast cancer cells is recently
      shown to be related to early distant recurrence and shortened survival. In this
      study, 163 patients with rectal cancer, included in the Swedish rectal cancer
      trial and followed up for a median of 71 months, were examined for the expression
      of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary
      tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101
      patients, 10 had CD163-positive cancers and these patients had earlier local
      recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those
      with CD163-negative tumors. When studying surgical specimens from 61 patients
      randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was
      found that 31% were CD163 positive whereas the corresponding figure was only 17%
      for 78 patients who were nonirradiated (p < 0.044), which tentatively may be
      consistent with X-rays inducing fusion. In CD163-positive tumors there was a
      reduced apoptotic activity as measured with the Termina deoxynucleotidyl
      Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There
      tended also to be an increased proliferation activity measured as an expression
      of Ki-67 non significant (NS). It is concluded that primary rectal cancers may
      express CD-163, and this phenotypic macrophage trait is related to early local
      recurrence, shorter survival time and reduced apoptosis. Furthermore, the
      expression of CD163 is more common after irradiation.

PMID- 19582879
TI  - Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo
      18beta-olean-1,12-dien-30-oate in colon cancer cells.
AB  - Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me) is a
      synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found
      in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer
      cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4
      protein and mRNA and several Sp-dependent genes including survivin, vascular
      endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me
      also induced apoptosis, arrested RKO and SW480 cells at G(2)/M, and inhibited
      tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me
      decreased expression of microRNA-27a (miR-27a), and this was accompanied by
      increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp
      repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit
      progression of cells through G(2)/M. Both CDODA-Me and antisense miR-27a induced
      comparable responses in RKO and SW480 cells, suggesting that the potent
      anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.

PMID- 19582881
TI  - Association of prostate stem cell antigen gene polymorphisms with the risk of
      stomach cancer in Japanese.
AB  - A recent whole-genome association study identified a strong association between
      polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer
      risk. In this case-control study, we aimed to validate this association, and
      further to explore environmental factors possibly interacting with PSCA
      polymorphisms in 708 incident stomach cancer cases and 708 age-sex matched
      controls. The association between PSCA polymorphisms and Helicobacter pylori
      infection was also examined. We found that rs2294008 and rs2976392, which were
      strongly linked to each other (D' = 1.00), were significantly associated with
      stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence
      interval: 1.19-1.65; p = 3.7 x 10(-5)). We found significant interaction with a
      family history of stomach cancer in first-degree relatives (p-heterogeneity =
      0.009). Similar to originally reported association, we found significant
      heterogeneity between diffuse and intestinal type (p-heterogeneity = 0.007). No
      association was seen between PSCA polymorphisms and H. pylori infection. In
      conclusion, PSCA polymorphisms are associated with stomach cancer risk in
      Japanese. A possible interaction with family history warrants further evaluation.

PMID- 19582882
TI  - Patterns of hematologic malignancies and solid tumors among 37,838 first-degree
      relatives of 13,896 patients with multiple myeloma in Sweden.
AB  - There are emerging data to suggest a role for genetic factors in the pathogenesis
      of multiple myeloma (MM). Based on small numbers, certain solid tumors have been
      reported to occur more frequently among blood relatives of patients with MM.
      Using population-based data, we assessed risks for hematologic malignancies,
      monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among
      first-degree relatives of patients with MM. We included 13,896 patients with MM
      and 54,365 matched controls. Also we identified first-degree relatives of
      patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal
      survival model, we estimated relative risks (RRs) and 95% confidence intervals
      (CIs) for hematologic and solid tumors among family members of patients with MM
      and controls as measures of familial aggregation. Compared with relatives of
      controls, relatives of patients with MM had an increased risk of developing MM
      (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia
      (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0
      1.5). No significantly increased risk was found for other hematologic or solid
      malignancies. Our findings support a role for a shared susceptibility (genetic,
      environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer.

PMID- 19582883
TI  - FGFR2 intronic polymorphisms interact with reproductive risk factors of breast
      cancer: results of a case control study in Japan.
AB  - Recently, 2 genome-wide association studies demonstrated that single nucleotide
      polymorphisms (SNPs) of the fibroblast growth factor receptor 2 (FGFR2) gene at
      intron 2 are significantly associated with the risk of female breast cancer. As
      the next step, it is necessary to evaluate the interaction between these SNPs and
      known risk factors of breast cancer because such an evaluation could elucidate
      mechanisms of carcinogenesis and lead to preventive advances. We conducted a case
      control study of 456 newly and histologically diagnosed breast cancer cases and
      912 age- and menopausal status-matched noncancer controls. The impact of 5 FGFR2
      intronic SNPs on the risk of breast cancer and the interactions between these
      SNPs and various known risk factors of breast cancer were evaluated in both pre
      and postmenopausal women. We observed a statistically significant association
      between 4 SNPs and breast cancer risk and these 4 SNPs were in strong linkage
      disequilibrium in the Japanese population. rs2420946 was associated with a
      population-attributable risk of 17.7%. We found that FGFR2 polymorphisms interact
      with family history of breast cancer (interaction p = 0.003) and reproductive
      risk factors, namely, age at menarche (interaction p = 0.019) and parity
      (interaction p = 0.026). Of note, a significant association between body mass
      index (BMI) > or = 25 and FGFR2 polymorphism was observed among postmenopausal
      women (trend p = 0.012), but not among premenopausal women. In contrast, BMI < 25
      had no significant association with this polymorphism regardless of menopausal
      status. These findings suggest that FGFR2 intronic SNPs affect the reproductive
      hormone-related pathway and contribute to the development of female breast cancer
      in the Japanese population.

PMID- 19582885
TI  - Unmasking the impostor.

PMID- 19582884
TI  - Investigating the potential of Bacillus subtilis alpha-amylase as a pressure
      temperature-time indicator for high hydrostatic pressure pasteurization
      processes.
AB  - The potential of Bacillus subtilis alpha-amylase (BSA) as a pressure-temperature
      time indicator (pTTI) for high pressure pasteurization processing (400-600 MPa;
      T(i) 10-40 degrees C; 1-15 min) was investigated. A stepwise approach was
      followed for the development of an enzyme-based, extrinsic, isolated pTTI. First,
      based on literature data on the pressure stability, BSA was selected as a
      candidate indicator. Next to the accuracy and ease of the measurement of the
      indicator's response (residual activity) to the pressure treatment, the storage
      and handling stability of BSA at atmospheric pressure was verified. Second, the
      stability of BSA at a constant temperature (T) and time in function of pressure
      (p) was investigated. Solvent engineering was used to shift the inactivation
      window of BSA in the processing range of interest. Third, the enzyme (1 g/L BSA
      MES 0.05 M pH 5.0) was kinetically calibrated under isobaric-isothermal
      conditions. Time dependent changes in activity could be modeled best by a first
      order model. Except for low pressures and high temperatures, a synergistic effect
      between pressure and temperature could be observed. Based on the model selected
      to describe the combined p,T-dependency of the inactivation rate constant, an
      elliptically shaped isorate contour plot could be constructed, illustrating the
      processing range where BSA can be used to demonstrate temperature gradients.
      Fourth, the validity of the kinetic model was tested successfully under dynamic
      conditions similar to those used in food industry. Finally, the indicator was
      found suitable to demonstrate nonuniformity in two-sectional planes of a
      vertical, single vessel system.

PMID- 19582888
TI  - The Obama effect?

PMID- 19582886
TI  - Laminin gamma2 mediates Wnt5a-induced invasion of gastric cancer cells.
AB  - BACKGROUND & AIMS: Wnt5a expression stimulates in vitro migration and invasion of
      cultured gastric cancer cells by an unknown mechanism and is also correlated with
      aggressiveness of gastric tumors. The aim of this study was to show that Wnt5a is
      involved in metastasis of gastric cancer cells in vivo and to explore the
      molecular mechanism by which Wnt5a regulates migration and invasion. METHODS: In
      an experimental liver metastasis assay, Wnt5a-knockdown gastric cancer cells were
      injected into the spleens of nude mice. Microarray analyses were used to compare
      expression patterns between mouse fibroblast L cells that stably express wild
      type and a mutant form of Wnt5a to investigate Wnt5a-dependent gene expression.
      The expression of genes found to be regulated by Wnt5a was investigated in
      cultured gastric cancer cells. Immunohistochemical analyses were performed to
      measure levels of Wnt-regulated gene products in 153 gastric cancer samples.
      RESULTS: Knockdown of Wnt5a in gastric cancer cells reduced the number of liver
      metastases that formed in nude mice. Microarray analyses indicated that Wnt5a
      activity induced expression of the gene encoding laminin gamma2, a subunit of the
      epithelial basement membrane protein laminin-5. Wnt5a induced the expression of
      laminin gamma2 through the activation of protein kinase C and c-Jun-N-terminal
      kinase. The invasive activity of gastric cancer cells depended on laminin gamma2;
      Wnt5a expression levels correlated with those of laminin gamma2 in diffuse
      scattered type gastric tumor samples from patients. CONCLUSIONS: Wnt5a
      contributes to gastric cancer progression by increasing metastatic potential.
      Wnt5a up-regulates laminin gamma2 to mediate gastric cancer cell aggressiveness.

PMID- 19582887
TI  - Negative mood affects brain processing of visceral sensation.
AB  - BACKGROUND & AIMS: A link between negative emotional state and abnormal visceral
      sensation has been frequently reported. However, the influence of negative
      emotion on brain processing of painful visceral sensations has not been
      investigated. We used functional magnetic resonance imaging (fMRI) and negative
      emotional stimuli to investigate the effects of negative emotion on brain
      processing of esophageal sensation. METHODS: Twelve healthy male volunteers (age
      range, 21-32 years) participated in the study. Negative emotion was induced using
      emotionally valent music. fMRI images were acquired during 2 experimental runs;
      throughout these, volunteers received randomized nonpainful and painful
      distentions to the esophagus during neutral and negative emotion. Subjective
      perception of each stimulus was acquired, as were mood ratings. RESULTS: Sadness
      ratings increased significantly following negative mood induction (P < .01).
      There was no significant effect of emotion on subjective perception of painful
      and nonpainful stimulation (P > .05). Following painful stimulation, brain
      activity increased in the right hemisphere during negative emotion and was
      localized to the anterior cingulate cortex (ACC; BA24/32), anterior insula, and
      inferior frontal gyrus. Following nonpainful stimulation during negative emotion,
      brain activity increased in the right anterior insula and ACC (BA24 and 32).
      CONCLUSIONS: This study provides new information about the influence of negative
      affect on central processing of visceral pain. Evidence of right hemispheric
      dominance during negative emotion indicates this hemisphere is predominately
      associated with sympathetic activity (arousal, negative affect) and that the
      right insula and right ACC are integral to subjective awareness of emotion
      through interoception.

PMID- 19582889
TI  - Russia's health promotion efforts blossom.

PMID- 19582890
TI  - Is disease eradication ethical?

PMID- 19582891
TI  - Passengers play a key part in road safety in Kenya.

PMID- 19582892
TI  - [Betablockers and noncardiac surgery: time to revisit strategies?].

PMID- 19582893
TI  - Granulocytic sarcoma.

PMID- 19582894
TI  - Mitochondrial tubulopathy in tenofovir disoproxil fumarate-treated rats.
AB  - OBJECTIVES: Tenofovir disoproxil fumarate (tenofovir DF) use has been associated
      with renal dysfunction and Fanconi syndrome. Tenofovir is taken up into renal
      tubules by anion transporters where high intracellular drug concentration may
      induce a functionally relevant depletion of mitochondrial DNA (mtDNA). We
      investigated if tenofovir may induce renal mtDNA depletion and respiratory chain
      dysfunction. METHODS: Rats (n = 8) were gavaged daily with 100 mg x kg(-1) x d(
      1) of tenofovir DF or didanosine. Kidneys and livers were examined after 8 weeks
      of treatment. RESULTS: The tenofovir group had significantly lower body and
      kidney weights than rats exposed to water or didanosine. Proximal but not distal
      tubules were of increased diameter and contained small lipid droplets. Tubular
      mitochondria were enlarged, and their crystal architecture was disrupted.
      Tenofovir-exposed kidneys contained low mtDNA copy numbers and impaired
      expression of mtDNA-encoded cytochrome c oxidase (COX) I but not nucleus-encoded
      COX IV subunits. Histochemistry demonstrated low tubular COX and nicotinamide
      adenine dinucleotide dehydrogenase (NADH-DH) activities, whereas succinate
      dehydrogenase activity was preserved. COX activity was preserved in the glomeruli
      of tenofovir-exposed rats. Didanosine did not elicit renal effects but, unlike
      tenofovir, depleted mtDNA in liver (by 52%). CONCLUSIONS: Tenofovir DF induces an
      organ-specific nephrotoxicity with mtDNA depletion and dysfunction of mtDNA
      encoded respiratory chain subunits. The data do not support nephrotoxicity of
      didanosine.

PMID- 19582896
TI  - HIV-1 genetic diversity and transmitted drug resistance in health care settings
      in Maputo, Mozambique.
AB  - OBJECTIVES: To characterize HIV-1 diversity and transmitted drug resistance in
      persons with access to care and treatment in Maputo, Mozambique. METHODS: Samples
      were collected in 2002-2004 from 144 drug-naive patients attending public
      hospitals and private clinics. Plasma viremia, CD4, and CD8 cell counts were
      determined for each patient. The Stanford Algorithm was used for resistance
      genotyping on pol sequences. Subtyping was done by phylogenetic analysis.
      RESULTS: Most patients had high viral load (mean, 5.0 log copies/mL) and low CD4
      cell counts (median, 260 CD4 cells/microL). Protease and/or reverse transcriptase
      sequences were obtained from 104 (72%) samples. Patients harbored subtypes C
      (80.8%), G (3.8%), CRF37_cpx (6.7%), untypable (U) (1.0%), and recombinant
      strains (7.7%) comprising the A, C, D, F, and U clades. There were no major
      protease inhibitor resistance mutations. Mutations conferring resistance to the
      nucleoside/nucleotide reverse transcriptase inhibitors and/or nonnucleoside
      reverse transcriptase inhibitors were found in 4 (4/68; 5.9%) patients.
      Phylogenetic analysis suggested an imported origin for 2 resistant variants.
      CONCLUSIONS: The HIV-1 epidemic in Maputo is evolving rapidly in genetic
      complexity due to the recent introduction of all major subtypes and recombinant
      forms. Continued surveillance of drug resistance in treated and untreated
      populations is needed to prevent further transmission of HIV drug-resistant
      variants and maximize the efficacy of antiretroviral therapy in Maputo.

PMID- 19582895
TI  - HIV testing rates and outcomes in a South African community, 2001-2006:
      implications for expanded screening policies.
AB  - BACKGROUND: Revised World Health Organization recommendations seek to increase
      HIV testing. We assessed the need for expanded testing in South Africa by
      examining current testing and treatment trends among a high prevalence
      population. METHODS: We determined the numbers of adults receiving HIV testing
      and antiretroviral treatment (ART) during 2001-2006 using testing registers
      linked to patient records from 2 health care facilities believed responsible for
      virtually all HIV services available to the population. We evaluated annual
      population testing rates using census population counts; proportions of clients
      testing seropositive (yield); CD4 counts and World Health Organization stage at
      diagnosis; and ART initiation rates. RESULTS: HIV testing rates rose from 4% in
      2001 to 20% in 2006 (P < 0.001) and were highest among pregnant females receiving
      provider-initiated testing. Yield for first-time testers decreased from 47% in
      2001 to 28% in 2006; annual incidence of seroconversion among initially HIV
      negative retesters was 1.9%. Median CD4 counts and World Health Organization
      stage distributions for newly diagnosed clients remained stable. HIV-infected
      clients receiving ART within 6 months of eligibility increased from 0% in 2001 to
      68% in 2006 (P < 0.001). CONCLUSIONS: Population testing and ART initiation rates
      rose dramatically during 2001-2006. Yet, yield remained high, and HIV-infected
      persons continued to receive late diagnoses. These findings highlight the
      continuing need for expanded testing and linkage to care.

PMID- 19582897
TI  - Modelling based on Australian HIV notifications data suggests homosexual age
      mixing is primarily assortative.
AB  - OBJECTIVE: To understand age-specific sexual mixing patterns of men who have sex
      with men in Australia, for behavioral insight, and to determine which age groups
      are at greatest risk of acquiring HIV in the future. METHODS: Diagnoses data
      based on Australia's HIV surveillance system are analyzed with a mathematical
      sexual transmission model to estimate the age-mixing patterns of sexual
      partnerships amongst men who have sex with men. The degree of assortativity and
      the relative rate of partner acquisition across different age groups are
      estimated. RESULTS: Although there are some differences between age groups,
      sexual mixing is primarily assortative for men of all ages, between completely
      random partner acquisition and fully assortative mixing, with greatest
      assortativity among middle-aged men. Men aged 25-34 years were shown to have the
      greatest level of sexual partner acquisition. There is little evidence to support
      disassortative mixing on average across the population. CONCLUSIONS: Although
      there is a tendency for partners of a similar age to be chosen and the average
      age of HIV-infected people in Australia is relatively old, suggesting that the
      epidemic may eventually age out depending on death rates, there seems to be
      sufficient cross-age mixing and high sexual mixing in younger age groups to
      sustain the HIV epidemic over the medium to long term.

PMID- 19582898
TI  - Pierluigi Nicotera. Interviewed by Karen Kaplan.

PMID- 19582899
TI  - If I deliver the baby now.

PMID- 19582900
TI  - Aurora1 phosphorylation activity on histone H3 and its  cross-talk with other
      post-translational histone  modifications in Arabidopsis.
AB  - The enzymological properties of AtAurora1, a kinase responsible for the cell
      cycle-dependent phosphorylation of histone H3 at S10, and its cross-talk with
      other post-translational histone modifications, were determined. In vitro
      phosphorylation of H3S10 by AtAurora1 is strongly increased by K9 acetylation,
      and decreased by K14 acetylation and T11 phosphorylation. However, S10
      phosphorylation activity is unaltered by mono-, di- or trimethylation of K9. An
      interference of H3K9 dimethylation by SUVR4 occurs by a pre-existing
      phosphorylation at S10. Hence, cross-talk in plants exists between
      phosphorylation of H3S10 and methylation, acetylation or phosphorylation of
      neighbouring amino acid residues. AtAurora1 undergoes autophosphorylation in vivo
      regardless of the presence of substrate, and forms dimers in planta. Of the three
      ATP-competitive Aurora inhibitors tested, Hesperadin was most effective in
      reducing the in vivo kinase activity of AtAurora1. Hesperadin consistently
      inhibited histone H3S10 phosphorylation during mitosis in Arabidopsis cells, but
      did not affect other H3 post-translational modifications, suggesting a specific
      inhibition of AtAurora in vivo. Inactivation of AtAurora also caused lagging
      chromosomes in a number of anaphase cells, but, unlike the situation in mammalian
      cells, Hesperadin did not influence the microtubule dynamics in dividing cells.

PMID- 19582901
TI  - Mentoring: a key strategy to prepare the next generation of physicians to care
      for an aging America.
AB  - Mentoring is an important instructional strategy that should be maximally used to
      develop the next generation of physicians who will care for a growing population
      of frail older adults. Mentoring can fulfill three specific purposes: (1) help
      learners choose an area of specialty, (2) help fellows and new faculty navigate
      advancement in the academic environment, and (3) help new physicians enter a
      local medical community and develop a high-quality, professionally rewarding,
      financially viable practice that meets the needs of older adults. The components
      and process of mentoring are reviewed. Current and potential mechanisms to
      promote mentoring for the specific purpose of increasing the quality and quantity
      of physicians available to care for the older adult population are discussed.

PMID- 19582902
TI  - Caregiving behind bars: correctional officer reports of disability in geriatric
      prisoners.
AB  - Despite increasing numbers of geriatric prisoners, little is known about
      geriatric disability or health care in prison. Although correctional officers
      often act as a liaison between prisoners and the healthcare system, the role of
      officers in recognizing geriatric disability has not been characterized. The
      goals of this study were to assess officers' assessment of disability in their
      assigned geriatric prisoners and to contrast their views with reports from the
      California Department of Corrections and Rehabilitation (CDCR). Questionnaires
      were given to 71 officers assigned to 618 randomly selected geriatric prisoners
      in 11 prisons. Information about 41 additional prisoners identified by
      correctional officers as "high risk" was also analyzed. Prisoner disability and
      health were determined through correctional officer questionnaires (activity of
      daily living (ADL) impairment, geriatric syndromes, level of care), chart review
      (medical diagnoses), and CDCR data (demographics, disability designation).
      Overall, 211 (34.1%) geriatric prisoners were unknown to their officer. Of the
      407 known prisoners, officers reported that 5.0% had ADL impairment and 3.1% were
      unsafe. Discordance between officer and CDCR reports of disability was common,
      with officers reporting higher disability rates. The 41 high-risk prisoners were
      more likely to have ADL impairment (22.0% vs 5.2%, P<.01) and geriatric syndromes
      such as falls and incontinence than the random sample. Overall, nearly one-third
      of geriatric prisoners were unknown to their assigned officer. Officers
      identified more disability than the CDCR, and prisoners they identified as high
      risk had nursing home-level functional impairments. Significant improvement in
      disability assessment is needed for officers and the CDCR.

PMID- 19582904
TI  - Under the gun.
AB  - The first recommendations on "meaningful use" got mixed reviews. Some said the
      federal advisory panel heeded the advice of providers in phasing in the process
      of adopting IT, while others say the bar might have been set too high. Work group
      Co-chairman Paul Tang, left, says the group had to strike a balance between too
      limited and too complicated definitions.

PMID- 19582906
TI  - AMA's moment. Obama visit makes news, but group's role unsure.

PMID- 19582905
TI  - Arguing over money. Reform debate turns to costs, reimbursement cuts.

PMID- 19582907
TI  - Emphasizing payment. Doc groups see reform through reimbursement prism.

PMID- 19582903
TI  - PIKfyve regulation of endosome-linked pathways.
AB  - The phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of
      PtdIns(3,5)P2, that has been implicated in various trafficking events associated
      with the endocytic pathway. We have now directly compared the effects of siRNA
      mediated knockdown of PIKfyve in HeLa cells with a specific pharmacological
      inhibitor of enzyme activity. Both approaches induce changes in the distribution
      of CI-M6PR and trans-Golgi network (TGN)-46 proteins, which cycles between
      endosomes and TGN, leading to their accumulation in dispersed punctae, whilst the
      TGN marker golgin-245 retains a perinuclear disposition. Trafficking of CD8-CI
      M6PR (retromer-dependent) and CD8-Furin (retromer-independent) chimeras from the
      cell surface to the TGN is delayed following drug administration, as is the
      transport of the Shiga toxin B-subunit. siRNA knockdown of PIKfyve produced no
      defect in epidermal growth factor receptor (EGFR) degradation, unless combined
      with knockdown of its activator molecule Vac14, suggesting that a low threshold
      of PtdIns(3,5)P2 is necessary and sufficient for this pathway. Accordingly
      pharmacological inhibition of PIKfyve results in a profound block to the
      lysosomal degradation of activated epidermal growth factor (EGF) and Met
      receptors. Immunofluorescence revealed EGF receptors to be trapped in the
      interior of a swollen endosomal compartment. In cells starved of amino acids,
      PIKfyve inhibition leads to the accumulation of the lipidated form of GFP-LC3, a
      marker of autophagosomal structures, which can be visualized as fluorescent
      punctae. We suggest that PIKfyve inhibition may render the late endosome/lysosome
      compartment refractory to fusion with both autophagosomes and with EGFR
      containing multivesicular bodies.

PMID- 19582908
TI  - Catholic labor's guiding light? U.S. bishops' conference to release 'blue print'
      for management on union issues.

PMID- 19582909
TI  - Being held accountable. Scrushy ordered to pay billions; L.A. exec pleads guilty.

PMID- 19582910
TI  - Out of the debate. Immigrants are missing quotient in reform talks.

PMID- 19582911
TI  - Dueling views. Dems support employer mandates, business doesn't.

PMID- 19582912
TI  - Dealing with personnel issues. To cut costs, systems seek ways to boost
      production, such as streamlining services.

PMID- 19582913
TI  - Tough times could get tougher. Attendees concerned over possible reimbursement
      cuts.

PMID- 19582914
TI  - ["Inspire the taste for innovation in nurses, in the service of collective
      quality"].

PMID- 19582915
TI  - [Nutrition from conception until birth, certainty and perspectives].

PMID- 19582916
TI  - Medication safety. Hospital, drug-maker team up to test new error reporting
      system.

PMID- 19582917
TI  - The power of payer data in health care reform.

PMID- 19582918
TI  - Leaders in transparency.

PMID- 19582919
TI  - On training.

PMID- 19582920
TI  - Working time directive. Quality time.

PMID- 19582921
TI  - Waiting times. First class posts.

PMID- 19582922
TI  - Skills development. Trade secrets.

PMID- 19582923
TI  - Training. You're hired.

PMID- 19582924
TI  - PCTs find there are no shortcuts to freedom.

PMID- 19582925
TI  - On caveats for consolidation.

PMID- 19582926
TI  - On what PCTs must prioritise.

PMID- 19582927
TI  - Staff wellbeing. What works for your workforce.

PMID- 19582928
TI  - Patient safety. Make sure your trust is a place of greater safety.

PMID- 19582929
TI  - Patient access. Hanging on the telephone.
AB  - Understaffed GP practices are unable to answer all patients' calls at peak times,
      such as Monday mornings. A third of practices have too few slots to meet expected
      levels of demand. Those that can meet demand do so through "complex and chaotic"
      processes. Lack of incentives means in-hours unscheduled care is being neglected.

PMID- 19582930
TI  - 'All bets are off' warns Nicholson as he tells NHS to prepare now for cuts.

PMID- 19582931
TI  - Trusts told to 'keep slogging' at infection control.

PMID- 19582932
TI  - Professionals in power: the czars' first 10 years.

PMID- 19582933
TI  - On toothless dental policy.

PMID- 19582934
TI  - On the Griffiths legacy.

PMID- 19582935
TI  - Voluntary workforce. Volunteers take a little and give a lot.

PMID- 19582936
TI  - Patient safety. Eat, drink and be healthy: malnutrition on the wards.

PMID- 19582937
TI  - General management. The power and the glory.
AB  - Consensus management was seen as decision making by the "lowest common
      denominator". General management was the way to measure cost benefits and achieve
      efficiency, said Griffiths. Within three years of Griffiths, there were 100
      nurses in unit and district general manager posts.

PMID- 19582938
TI  - Self care. Help yourself.

PMID- 19582939
TI  - Reform. In for the long haul.

PMID- 19582940
TI  - Re: O'Neill JP, Fenton JE. The recurrent laryngeal nerve in thyroid surgery.
      Surgeon 2008 6; 6: 373-7.

PMID- 19582941
TI  - Two-way street between depression and heart disease.  Lifting depression can help
      the heart; exercise is essential.

PMID- 19582942
TI  - Diet and attention deficit hyperactivity disorder.  Can some food additives or
      nutrients affect symptoms?  The jury is still out.

PMID- 19582944
TI  - Schizophrenia and bipolar disorder may share genetic origins.

PMID- 19582943
TI  - Coping with the stress of caregiving.  Caring for someone with a brain disorder
      can be especially hard.

PMID- 19582945
TI  - Questions and answers.  If I have obsessions or compulsions, does it mean that I
      have obsessive-compulsive disorder?

PMID- 19582947
TI  - Theses in the Osler Library including that of Pierre de Sales Laterriere.

PMID- 19582946
TI  - Montreal, medicine and William Leslie Logie: McGill's first graduate and Canada's
      first medical graduate. 175th anniversary, 1833-2008.

PMID- 19582948
TI  - All's fair in love, war and anatomical atlas publishing.

PMID- 19582949
TI  - The Oslers and Charles Darwin.

PMID- 19582950
TI  - Explaining long term trends in violent crime.

PMID- 19582952
TI  - Does correcting hyponatremia improve liver transplant outcomes?

PMID- 19582951
TI  - "Lies, damned lies and criminal statistics": reinterpreting the criminal
      statistics in England and Wales.

PMID- 19582954
TI  - Follow-up on platelet transfusion causing decreased postoperative survival after
      liver transplantation.

PMID- 19582953
TI  - Is there any benefit to laparoscopic liver resection for hepatocellular carcinoma
      if a salvage liver transplant is needed later?

PMID- 19582955
TI  - "The administration of discipline by the English is very rigid": British military
      law and the death penalty (1868-1918).

PMID- 19582956
TI  - [Child abuse in Swaziland].

PMID- 19582957
TI  - [National Society of Nurses, 23 regions, 23 presidents (6/6). Interview by Serge
      Benaderette].

PMID- 19582958
TI  - [Independent Ethics Committees for clinical research in Argentina. An evaluation
      and a system to guarantee their independence].

PMID- 19582959
TI  - [Living with HIV today].

PMID- 19582960
TI  - Setting a national minimum standard for health benefits: how do state benefit
      mandates compare with benefits in large-group plans?
AB  - Many proposed health insurance reforms would establish a federal minimum benefit
      standard--a baseline set of benefits to ensure that people have adequate coverage
      and financial protection when they purchase insurance. Currently, benefit
      mandates are set at the state level; these vary greatly across states and
      generally target specific areas rather than set an overall standard for what
      qualifies as health insurance. This issue brief considers what a broad federal
      minimum standard might look like by comparing existing state benefit mandates
      with the services and providers covered under the Federal Employees Health
      Benefits Program (FEHBP) Blue Cross and Blue Shield standard benefit package, an
      example of minimum creditable coverage that reflects current standard practice
      among employer-sponsored health plans. With few exceptions, benefits in the FEHBP
      standard option either meet or exceed those that state mandates require
      indicating that a broad-based national benefit standard would include most
      existing state benefit mandates.

PMID- 19582961
TI  - Menopause medicine: exercise and weight gain.

PMID- 19582962
TI  - Taking care of everything.

PMID- 19582963
TI  - Guidelines for hand hygiene in healthcare settings.

PMID- 19582964
TI  - The mature minor exception and the provision of medical treatment.

PMID- 19582965
TI  - Umbilical cord blood storage for the public good.

PMID- 19582966
TI  - Where have all the primary care doctors gone?

PMID- 19582967
TI  - The role of simulation in medical education.

PMID- 19582968
TI  - Epidermolysis bullosa acquisita in an 18-year-old African-American male: a case
      report.
AB  - An 18-year-old African-American male with epidermolysis bullosa acquisita
      presenting as vesico-bullous lesions over the fingers, elbows and knees following
      minimal trauma is reported. There was no underlying systemic disease, and he
      responded to administration of dapsone and prednisone.

PMID- 19582969
TI  - The controversy associated with long-acting beta2-agonists in asthmatic patients.

PMID- 19582970
TI  - Updates to the "Welcome to Medicare" exam.

PMID- 19582971
TI  - The hot toe.

PMID- 19582972
TI  - Calming troubled waters.

PMID- 19582973
TI  - Nursing: making a difference.

PMID- 19582974
TI  - Health care reform that cannot wait.

PMID- 19582975
TI  - Statement regarding seasonal influenza vaccination for registered nurses and
      other health care personnel.

PMID- 19582977
TI  - A peek at the plan.

PMID- 19582976
TI  - Sugar blues.

PMID- 19582978
TI  - Climate and health: one diagnosis, multiple prescriptions.

PMID- 19582980
TI  - A clinical decision support system using multilayer perceptron neural network to
      assess well being in diabetes.
AB  - BACKGROUND: Diabetes mellitus is an increasingly common life-style disorder whose
      management outcomes are measured in symptomatic, biochemical as well as
      psychological areas. Well being as an outcome of treatment is being increasingly
      recognized as a crucial component of treatment. There is little published
      literature on psychosocial outcomes and the factors influencing them. Therefore
      we have developed a neural network system which is trained to predict the well
      being in diabetes, using data generated in real life. MATERIAL AND METHODS: We
      developed a Multi Layer Perceptron Neural Network model, which had been trained
      by back propagation algorithm. Data was used from a cohort of 241 individuals
      with diabetes. We used age, gender, weight, fasting plasma glucose as a set of
      inputs and predicted measures of well-being (depression, anxiety, energy and
      positive well-being). RESULTS: It was observed that female patients report
      significantly higher levels of depression than their male counter parts. Some
      slight high or no significant differences are observed between males and female
      patients with regard to the number of persons with whom they share their
      anxieties and fears regarding diabetes. There is not much difference has been
      observed in energy levels of both males and females. Also, Males have higher pwb
      value when compared with the female counterparts. Also, this may be due to women
      tend to react more emotionally to disease and hence experience more difficulty in
      coping with it. The present sample of women being predominantly house wives may
      be worrying more about their health and its problems. Also, it is observed that,
      gender differences are significant with regard to total general well-being. With
      five inputs (age, sex, weight, fasting plasma glucose, bias), four outputs are
      four (depression, anxiety, energy and positive well-being) the momentum rate was
      0.9, the learning rate 0.7, using a sample of 50. the maximum individual error is
      0.001 when the number of iterations were 500, number of hidden layers is 1 and
      the number of units in the hidden layer are 6, the normalized system error was
      470.57. With input samples of 100, 150 and 200, keeping the other variables
      constant, the normalized system error was 419.61, 359.67 and 332.32 respectively.
      Similar values are found for the normalized system error when the number of units
      in the hidden layer have been increased to 7, 8 and 9 respectively. With two
      hidden layers, and with each hidden layer containing 6,7 ,8, 9, 10, 11 units for
      the samples 50, 100, 150, and 200, the same values of normalized system error was
      found. Women having weight between 40 kgs and 85kgs had higher levels of
      depression than men who had weight between 39kgs and 102 kgs. CONCLUSION: We have
      developed a prototype neural network model to predict the psychosocial well-being
      in diabetes, when biological or biographical variables are given as inputs. When
      greater data was fed to the system, the normalized system error can be reduced.

PMID- 19582979
TI  - The malaria severity score: a method for severity assessment and risk prediction
      of hospital mortality for falciparum malaria in adults.
AB  - BACKGROUND: There is paucity of research to quantify the severity and to predict
      the mortality risk of severe falciparum malaria even if it affects multiple organ
      systems during the course of the disease. Therefore, the aim of the present study
      is to develop a severity score for assessment of disease severity and risk
      prediction in adult patients of severe falciparum malaria on the first day of
      hospitalisation. METHODS: A cohort of 2598 patients of falciparum malaria were
      enrolled in this study of which 2089 patients were included as developmental
      sample and 509 patients as validation sample. Physiological variables were
      analyzed for defining and assessment of severity of organ dysfunction (OD). The
      severity level and corresponding severity score for each organ dysfunction were
      determined by logistic regression analysis that took both the relative severity
      among the organ systems and the degree of severity within an organ system into
      account. Risk of mortality has been calculated for each score. RESULTS:
      Physiological variables defined dysfunction in 7 organ systems with 3 levels of
      severity (I to III). Neurologic and renal dysfunction had 3 levels of severity.
      Hematologic, cardiovascular, and respiratory dysfunction had 2 levels of severity
      where as hepatic and metabolic dysfunction had 1 level of severity. 1,3, and 5
      points were assigned to level I, II, and III severity of organ dysfunction
      respectively. Malaria without any abnormal physiological variables had been
      considered as no organ failure and assigned 0 score. The cumulative scores in a
      patient is known as malaria severity score (MSS) that ranged from 0 to 21. Risk
      of mortality had been calculated for each score. CONCLUSION: This prospective
      study provides an objective tool for assessing severity levels for organ
      dysfunction and prediction of risk of mortality in severe falciparum malaria
      which can be used for treatment and research. It has been observed that no two
      patients of falciparum malaria are same in severity. The severity varies over
      time and malaria can affect single or multiple organs with different levels of
      severity which can be quantified as level I, II, and III. Neurologic and renal
      dysfunction were the most severe with level III severity, followed by
      haematologic, cardiovascular, and respiratory dysfunction with level-II severity,
      as well as hepatic and metabolic dysfunction the least severe with level-I
      severity. Patient of malaria can be stratified as low, intermediate, and high
      risk depending on the MSS. With the help of MSS daily risk estimates and recovery
      time of OD can be determined.

PMID- 19582981
TI  - Prevalence of coronary risk factors in type 2 diabetics without manifestations of
      overt coronary heart disease.
AB  - AIMS: To find the prevalence of cardiovascular risk factors in type-2 diabetics
      without manifestations of overt coronary heart disease and to estimate the
      prevalence of silent myocardial ischaemia in these patients. METHODS: Seventy
      seven patients of type 2 diabetes were recruited for the study (one patient lost
      after recruitment; 76 completed the study). History and physical examination were
      recorded. Laboratory investigations included fasting and 2-hour post-prandial
      blood sugar, blood urea, serum creatinine, lipid profile, glycated haemoglobin,
      and microalbuminuria. Ultrasonographic scanning of the carotid arteries was
      performed to measure the carotid IMT. For identification of cases of silent
      ischaemia, treadmill test (TMT) was performed. RESULTS: The study group was
      divided into a non-CAD group (n=54), and a silent CAD group (n=22). Twenty-two
      diabetics were found to have silent CAD as evidenced by a positive TMT result
      (28.9%). The prevalence of silent myocardial ischaemia was almost similar in both
      males and females. Serum LDL levels more than 140 mg% had a significant
      correlation with the prevalence of silent CAD (p = 0.04). The difference in CCA
      IMT values was found to be statistically significant between the silent CAD and
      non-CAD groups (p = 0.019). CONCLUSION: High LDL level and greater carotid intima
      media thickness are particularly important parameters that can predict if a
      patient of type 2 diabetes is at risk for silent ischaemia. A high carotid IMT is
      a surrogate and reliable marker of higher risk of CAD amongst type 2 diabetic
      patients, even in those without overt CAD. The study also underlines the utility
      of carotid IMT as a simple, non-invasive, safe, and cheap screening test for the
      assessment of risk of CAD in type 2 diabetics.

PMID- 19582982
TI  - Reliability and validity of a modified PHQ-9 item inventory (PHQ-12) as a
      screening instrument for assessing depression in Asian Indians (CURES-65).
AB  - OBJECTIVES: To evaluate the validity and reliability of the modified Patient
      Health Questionnaire(PHQ) 12 item instrument as a screening tool for assessing
      depression compared to the PHQ-9 in a representative south Indian urban
      population. METHODS: The Chennai Urban Rural Epidemiology Study [CURES] is a
      large cross-sectional study conducted in Chennai, South India. In Phase 1 of
      CURES(urban component), 26,001 individuals aged > or =20 years individuals were
      selected by a systematic sampling technique of whom one hundred subjects were
      randomly selected, using computer-generated numbers, for this validation study.
      Two self-reported questionnaires (modified PHQ-12 item and PHQ-9 item) were
      administered to the subjects to compare their effectiveness in detecting
      depression. Reliability and validity were assessed and Receiver Operating
      Characteristic (ROC) curves were plotted. Pearson's correlation was used to
      compare the two questionnaires. RESULTS: The mean age of the study was 38.6 +/-
      11.6 years and 48% were males. Pearson's correlation coefficient between the
      modified PHQ-12 and the PHQ-9 item was 0.913 [p < 0.0001]. Factor Analysis
      revealed that the modified PHQ-12 item scale can be used as a unidimensional
      scale and had excellent internal consistency (Cronbach's alpha: 0.88). A cut
      point of >4 calculated using the ROC curves for the modified PHQ-12 item had the
      highest sensitivity (92.0%) and specificity (90.7%) using PHQ-9 as the gold
      standard. The positive predictive value was 76.7%, and the negative predictive
      value, 97.1% and the area under the ROC curve, 0.979 (95% Confidence Interval:
      0.929 - 0.997, p < 0.0001). CONCLUSION: The modified PHQ-12 item is a valid and
      reliable instrument for large scale population based screening of depression in
      Asian Indians and a cut point score of greater than 4 gave the highest
      sensitivity and specificity.

PMID- 19582983
TI  - Scleroderma and hypermobility--an unusual combination.

PMID- 19582984
TI  - Atypical eschar sites in scrub typhus in sub-Himalayas.

PMID- 19582985
TI  - Whole grains and health: perspective for Asian Indians.
AB  - Grains are a part of human diet for about 10,000 years. Grains are the most
      important food source of Indian population, due to this carbohydrate consumption
      constitute approx. 60-70% of total food intake. Variety of grains are available
      in India, and different grains form staple diets of people in different part of
      the country. Whole grains are now recognized as an important source of fiber and
      other nutrients like trace minerals a vitamins. Grains have shown to have a role
      in prevention and reducing the risk of type 2 diabetes, coronary heart disease,
      cancer and obesity.

PMID- 19582987
TI  - Werner Forssmann--The Risk Taker. Stamps issued on Werner Forssmann and cardiac
      catheterization, Germany, 2006.

PMID- 19582988
TI  - Acute enteritis associated with pneumococcal bacteremia.
AB  - We describe an elderly male who had a two day history of fever, abdominal pain
      and watery loose motions. Clinical examination was positive for abdominal right
      lower quadrant tenderness and moderate dehydration. Stool examination revealed
      inflammatory diarrhea. Considering the high prevalence of extended spectrum beta
      lactamases (ESBL) producing Gram-negative infections, he was treated with
      Piperacillin/Tazobactam. Surprisingly, his blood culture which was taken on
      admission returned positive for Streptococcus pneumoniae after two days, which
      was coincident with resolution of fever and diarrhea. This patient had no other
      clinically apparent source of Pneumococcal infection and we believe that he had
      Pneumococcal enteritis with bacteremia. There are very few reported cases of
      isolated Pneumococcal enteritis in the literature. Therefore, we report this
      unusual form of Streptococcus pneumnoniae infection both because of its rarity
      and its potentially life-threatening but still curable nature.

PMID- 19582989
TI  - MRI imaging of ulnar leprosy abscess.
AB  - Leprosy is a chronic granulomatous infection, caused by mycobacterium leprae,
      primarily affecting the peripheral nerve trunks and cutaneous nerves. It
      classically presents with neural or dermal signs and symptoms. The indolent
      course of leprosy may manifest as erythema nodosum (appearance of tender inflamed
      subcutaneous nodule) and reversal reaction (inflammation in the previous skin
      lesion, appearance of new skin lesions, neuritis and abscess). Ulnar nerve is
      most commonly involved. This report illustrates the MR imaging appearance of
      ulnar nerve abscess.

PMID- 19582990
TI  - Syndrome of tubulointerstitial nephritis and uveitis.
AB  - We report a case of acute tubulointerstitial nephritis and uveitis syndrome (TINU
      syndrome) in an elderly Indian woman. TINU is one of the rare causes of acute
      tubulo interstitial nephritis and is likely to be missed as there is often
      temporal gap between the appearance of the renal and ocular manifestations.

PMID- 19582992
TI  - Bilateral breast hematoma following thrombolytic therapy.

PMID- 19582991
TI  - Unexpected and abnormally low HDL cholesterol levels on combination hypolipidemic
      therapy.
AB  - In general, Indians have low HDL cholesterol levels. Fenofibrate, a drug widely
      used in the treatment of hypertriglyceridemia, usually also increases HDL
      cholesterol. There have been a few reports in the literature of a paradoxical
      decrease in serum HDL-cholesterol in patients treated with fenofibrate, either
      alone or in combination with a statin. We report three cases of paradoxical
      decrease in serum HDL-cholesterol in type 2 diabetic patients treated with a
      statin-fenofibrate combination.

PMID- 19582994
TI  - [SBK must reflect on the strengths].

PMID- 19582993
TI  - Anaphylactic reaction to intravenous artesunate.

PMID- 19582995
TI  - [With our without open membership--both want a strong SBK (interview by Urs
      Luthi)].

PMID- 19582996
TI  - [Integration and exclusion--an ongoing conflict].

PMID- 19582997
TI  - [Prevention requires a sensitive touch].

PMID- 19582998
TI  - [Forum theater eliminates the taboo of the topic].

PMID- 19582986
TI  - Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic
      syndrome for Asian Indians and recommendations for physical activity, medical and
      surgical management.
AB  - Asian Indians exhibit unique features of obesity; excess body fat, abdominal
      adiposity, increased subcutaneous and intra-abdominal fat, and deposition of fat
      in ectopic sites (liver, muscle, etc.). Obesity is a major driver for the widely
      prevalent metabolic syndrome and type 2 diabetes mellitus (T2DM) in Asian Indians
      in India and those residing in other countries. Based on percentage body fat and
      morbidity data, limits of normal BMI are narrower and lower in Asian Indians than
      in white Caucasians. In this consensus statement, we present revised guidelines
      for diagnosis of obesity, abdominal obesity, the metabolic syndrome, physical
      activity, and drug therapy and bariatric surgery for obesity in Asian Indians
      after consultations with experts from various regions of India belonging to the
      following medical disciplines; internal medicine, metabolic diseases,
      endocrinology, nutrition, cardiology, exercise physiology, sports medicine and
      bariatric surgery, and representing reputed medical institutions, hospitals,
      government funded research institutions, and policy making bodies. It is
      estimated that by application of these guidelines, additional 10-15% of Indian
      population would be labeled as overweight/obese and would require appropriate
      management. Application of these guidelines on countrywide basis is also likely
      to have a deceleration effect on the escalating problem of T2DM and
      cardiovascular disease. These guidelines could be revised in future as
      appropriate, after another large and countrywide consensus process. Till that
      time, these should be used by clinicians, researchers and policymakers dealing
      with obesity and related diseases.

PMID- 19583000
TI  - [Professional triage increases safety and decreases workload].

PMID- 19582999
TI  - [Counseling, support and rest lead the way out of the low mood].

PMID- 19583001
TI  - [Structured assessment saves time].

PMID- 19583002
TI  - [Improved safety for personnel and patients].

PMID- 19583003
TI  - [Light modifies convalescence].

PMID- 19583004
TI  - ["Visionaries are needed who will dare to think differently (interview by Margrit
      Bachl)].

PMID- 19583005
TI  - [Understanding them--indispensible for nursing, helping, teaching].

PMID- 19583006
TI  - [Making life successful and prospering in life].

PMID- 19583007
TI  - [Geriatrics: the challenge of competence].

PMID- 19583008
TI  - [The possibility of having a third alternative].

PMID- 19583009
TI  - [Resistant bacteria threaten public health].

PMID- 19583010
TI  - [HSAN verdict--a setback for safer care].

PMID- 19583011
TI  - [Biosimilar products comparable to original preparations. The Medical Products
      Agency will not yet classify the agents as generics].

PMID- 19583012
TI  - [Darwin's principles direct the development of A/H1N1. Influenza virus evolution
      enormously complex--the new influenza is not and exception].

PMID- 19583014
TI  - [Biosimilar products--cheaper version of biological drugs. New possibilities
      within several therapeutic fields].

PMID- 19583013
TI  - [Fully possible to reduce the costs of hypertension treatment].

PMID- 19583015
TI  - [Initial management of open lower limb fractures].

PMID- 19583017
TI  - [The roundabout way of the circumcision].

PMID- 19583018
TI  - [Successful introduction to Hungarian physicians].

PMID- 19583016
TI  - [Investigation of suspected beta-lactam hypersensitivity].

PMID- 19583019
TI  - [The JUPITER study emphasizes primary prevention].

PMID- 19583020
TI  - [The zero vision creates new taboos].

PMID- 19583021
TI  - [Also elderly with polyneuropathic pain should get chance to pain relief].

PMID- 19583022
TI  - [Out-of-date about bipolar disease].

PMID- 19583023
TI  - [Here the artists compete for jobs in the health sector].

PMID- 19583024
TI  - [Two outbreaks of eosinophilic meningitis in Yunann (China) clinical,
      epidemiological and therapeutical issues].
AB  - Eosinophilic meningitis is an uncommon clinical entity, which is mostly caused by
      Angiostrongylus cantonensis, a nematode which parasitizes rat's lungs. Humans
      represent a dead-end in the parasite's lifecycle and become infected by ingesting
      snails, slugs or transport hosts. Due to uncontrolled proliferation and
      circulation of snails and rats, human angiostrongyliasis has emerged in new foci
      in continental China. The treatment, which relies upon a combination of
      albendazole and corticosteroids, is still a matter of debate. In order to assess
      the epidemiological features of two outbreaks which occurred in Kunming, capital
      of the Yunnan province, 2003 and 2005, along with the clinical and treatment
      issues, a retro-prospective study was carried out among thirty-four clinical
      cases of eosinophilic meningitis. Furthermore, a parasitological survey was
      carried out on randomized samples of snails sold in the markets of the city On
      admission, all cases were found to have acute headaches and an eosinophilic
      pleocytosis rate > 5% in the cerebro spinal fluid (CSF). All patients reported
      the consumption of raw snails Pomacea canaliculata, 14 days on average before the
      onset of headaches (range 1-30 days). Hyperesthesia due to radiculitis was
      observed in 68% of the cases and the meningitis syndrome was present in 41%. The
      average value of blood eosinophil count in CSF and in peripheral blood was 38%
      and 900/ml, respectively. Two treatment schedules were used (without
      randomization): one with progressive doses over 4 weeks; the other with immediate
      high doses for 10 days with 3 sessions separated by 14-day intervals. The results
      were compared by the Kaplan Meier log rank test. All the cases had a favorable
      evolution. The analysis suggested better effectiveness and tolerance of the
      albendazole - dexamethasone combination used at the highest dosage, namely
      20mglkg daily and 10mg daily respectively. Eosinophilic meningitis appeared to be
      recently emerging or re-emerging in Kunming. Deep-rooted culinary habits of
      eating raw food, and large amount of snails sold on local markets (about one ton
      per day) provide ideal conditions for the outbreak, or occurrence of this
      disease. According to the resdjlts of this study Chinese local authorities should
      be urged to improve information to the population about the risks of eating raw
      snails, in order to strengthen the control of both rat and snail populations and
      reinforce the supervision of local food markets.

PMID- 19583025
TI  - [Diagnosis of a cutaneous endometriosis decidualised and fistualized during
      pregnancy].
AB  - A case of a decidualized and fistulized cutaneous endometriosis has been observed
      in the obstretrical and gynecological department of the Yalgado-Ouedraogo
      national hospital. The patient was a 3-year-old pregnant woman in her third
      pregnancy primipara, without any surviving child, who presented with a large
      scabby exulcerated plaque on an hyperpigmented lesion, associated with para
      umbilical. The patient underwent 12 years earlier a laparotomy for peritonitis
      worsened with parietal suppuration, then by rupture. The lesion has made the
      diagnosis difficult and the histologist concluded that it was a decidualised
      cutaneous endometriosis. Based on this observation, the first one until now, the
      authors have made a publication on the case.

PMID- 19583026
TI  - [An uncommon localization of pyoderma gangrenosum on the penis of an HIV infected
      patient in the Ivory Coast].
AB  - Pyoderma gangrenosum is an uncommon chronic ulcerative dermatosis with unknown
      aetiology and with a pathology which is still obscure. In 15-45% of cases, it is
      related to intestinal chronic inflammatory disease (MICI), to a systemic disease
      that it can sometimes reveals or to an immunodeficiency This disease starts
      whether with a pustule, a bubble or a nodule which leads during its evolvement to
      a superficial ulceration with clear edges. Its diagnosis is easy and is mainly
      clinical. It is a disease which is localized preferably in lower limbs. Treatment
      is mainly based on oral route corticotherapy. We report a case of gangrenosum
      pyoderma localized on the penis in a 43-year-old HIV infected patient. It is an
      uncommon localization, misleading and delicate. We have treated successfully this
      patient by oral corticotherapy combined with local antiseptic treatments for 6
      months.

PMID- 19583027
TI  - [Unusual association of endomyocardial fibrosis and aberrant migration of
      Dracunculus medinensis in the pericardium].
AB  - We report one case of endomyocardial fibrosis with a relapsing pericarditis,
      associated with an aberrant migration of Dracunculus medinensis in the
      pericardium, in a 22-year-old patient from an endemic zone of bilharziasis and
      dracunculosis in Cote d'Ivoire. The evolution has been marked by the appearance
      of thrombus in the right atrium. The patient died on the 49th day of
      hospitalization following an refractory cardiac insufficiency.

PMID- 19583028
TI  - [Treatment's problem of osteoarticular infections in Madagascar].
AB  - The septic arthritis and osteitis treatment is based on germ(s) identification,
      which is not always obvious if we do not have at our disposal some proper
      technical platforms. Moreover, the population's low purchasing power compels us
      to prescribe the most affordable antibiotic. Regarding this context, this article
      is aimed at modelling a treatment strategy of osteoarticular infections for adult
      in developing countries, with international recommendations as our basis. It is a
      retrospective study, which concerned inpatients admitted in the rheumatology
      dermatology department of the Antananarivo University Hospital for septic
      arthritis and osteitis over all clinical patterns. We considered 9 cases
      including 7 septic arthritis and 2 osteitis. Staphylococcus aureus was found in
      two patients who had an osteitis, no germ was isolated for the patients with
      septic arthritis. Ceftriaxone 2 g per day combined with ciprofloxacine 1 g per
      day by IV route, shifted by oxacilline 3 g per day and by ciprofloxacine 1 g per
      day peroral proved to be effective for all patients. The international
      epidemiological data and the medicines cost were used as reference for the choice
      of antibiotics treatment. Our approach is worth being taken into consideration as
      an adaptation of the European recommendations to the realities of developing
      countries. In absence of any particular risk factor for any specific infection,
      the combination of ceftriaxone Iciprofloxacine IV route, shifted by
      oxacilline/ciprofloxacine peroral is recommended.

PMID- 19583029
TI  - [Two cases of probable immune restoration syndrome under antiretroviral treatment
      in patients treated for tuberculosis in Gabon].
AB  - Tuberculosis can be reactivated under specific treatment, as immune
      reconstitution inflammatory syndrome (IRIS), in HIV patients under antiretroviral
      treatment. We report two observations of tuberculosis exacerbation with extension
      to other territories (lymph node and pericarditis) occurring 3 weeks and 4 months
      after administration of tuberculosis treatment, with a favourable development, in
      absence of rehabilitation or addition of complementary therapy These observations
      show the necessity of increased surveillance on the short, medium and long term
      in patients with both treatment for tuberculosis and antiretroviral treatment.

PMID- 19583030
TI  - [Mitochondrial toxicity: a case of palpebral ptosis in a woman infected by HIV
      and treated with HAART including zidovudine].
AB  - The usual clinical feature of mitochondrial toxicity is proximal myopathy. We
      present the report case of palpebral ptosis which occurred under zidovudine
      therapy The symptom remission was obtained by stopping the antiretroviral
      therapy. This involves an important vigilance from both doctor and patient.

PMID- 19583031
TI  - [Tolerance study of a triple first-line antiretroviral combination zidovudine,
      lamivudine and efavirenz in Dakar, Senegal].
AB  - This study aimed at describing the side-effects reported in patients infected
      with HIV-1 treated initially by the association zidovudine, lamivudine and
      efavirenz between 2002 and 2007 in the Regional Centre of Clinical Research and
      Training in Dakar as part of the cohort of the Senegalese Initiative Access to
      Antiretroviral. Adverse effects were entered and analysed using the software Epi
      Info version 6.04. The average age of the patients was 38 years old. During the
      follow-up (average = 741 days), adverse effects were reported 75 times and 39
      patients were concerned. The most frequent type of side-effects was
      neuropsychiatric (47%), digestive (20%) and dermatological (16%). They were
      severe in 13% of cases and severe anaemia was noted in eight cases. These
      required a change of therapy in 19%, mainly for severe anaemia (15%). The
      association zidovudine, lamivudine and efavirenz doesn't seem to induce severe
      side-effects. Nevertheless, considering the frequency of neuropsychiatric side
      effects and severity of hematological side-effects, attention should be paid to
      neuropsychiatric and blood examination of patients undergoing this combination
      antiretroviral therapy.

PMID- 19583032
TI  - [Distribution and ecology of the Savannah human African trypanosomiasis vectors
      in disturbed forest zone in south Cameroon: about case in the Doume forest].
AB  - Vector control through trapping in the foci of humid forest areas is rather
      difficult because of the wide spreading of tsetse flies and transmission sites of
      human African trypanosomiasis. In fact, traps should be a priori set up
      everywhere to stop the transmission. The identification of the disease
      transmission sites enables efficient trapping through localisation of dangerous
      tsetse flies habitats needing vector control measures. The study of adult tsetse
      flies and teneral tsetse flies spatial distribution and human vector contacts was
      conducted in Doumb to determine the transmission of human African trypanosomiasis
      for efficient vector control. Glossina fuscipes fuscipes was the only tsetse fly
      captured with a very low apparent density of 0.13 tsetse flies per trap and per
      day. Furthermore, the disease transmission in the focus was not found uniform. In
      fact, human vector contacts are high in two villages (Paki and Mendin) located in
      the highly disturbed forest zones. These contacts occur in humid shallows where
      teneral tsetse flies were only captured around streams and forest galleries. The
      Doume focus presents therefore characteristics of savannah focus where river
      banks and nearby biotopes are the main target sites for vector control campaigns.

PMID- 19583033
TI  - [Five years of cholera surveillance in Ivory Coast during social and political
      crisis, 2001 to 2005].
AB  - For an efficient struggle against infectious diseases with epidemic potential,
      the Cdte d'Ivoire set up a precocious alert system in 2001 with a main objective:
      to detect epidemics of cholera, measles, yellow fever and meningitis and to
      provide necessary information for their control and their prevention. During the
      2001 to 2005 period, the country was marked by military and political crisis
      which occurred in 2002; the country had to face up to a reappearance of cholera.
      How did it evolve in such a context? The question was to describe the
      performances of the system and the evolution of cholera from weekly data
      collected by the centers of epidemiological monitoring in health districts. The
      cases and declared deaths were compiled and the indicators of morbidity and
      mortality were then studied according to time site and individual features on the
      period of 2001 to 2005. From 2001 to 2005, 11,874 cases were notified with 564
      deaths and a lethal rate of 4.7%. In 2001, from the initial source of infection,
      the civil jail, the epidemic of cholera disseminated itself through visitors in
      the whole city of Abidjan where 3250 cases were notified. Out of city, 20
      outbreaks have been declared with a total of 3010 cases. The yearly highest
      impact, 37 living cases/100,000 inhabitants recorded in 2001, decreased regularly
      until 2005 with 0.2 living cases/100,000. After 2002, outbreaks were located
      mainly in the half south of the country which welcomed displaced populations from
      the north, preferably in transition or settling zones near the front line. The
      lethal rate in Abidjan (2.3%) was less important than that of other health
      districts (8.6%). The lethal rate globally increased as the impact decreased.
      Vibrio cholerae was responsible for the epidemics. The group of 15 years old and
      over was the most affected (12.69 living cases/100,000) whereas the highest
      lethal rate appeared in the group under 5 years old (6.6%). The reappearance and
      constant cholera epidemics in Cote d'Ivoire are due to bad general hygiene
      conditions, insufficient supply of drinking water from wells or packaged,
      concentration of populations in the south of the country due to war and
      uncontrolled development of the poor and unsanitary precarious boroughs. Outburst
      during the dry season is a warning signal of an important epidemic during the
      raining season especially in poor urban areas. The precocious alert system has
      permitted to detect the epidemics, to follow up their evolution and to orientate
      the struggle against cholera in Cote d'Ivoire.

PMID- 19583034
TI  - [Assessment of antibiotics prescribing for outpatients in Cotonou, Benin].
AB  - The objective was to study antibiotics prescribing in Cotonou health care
      centres. This prospective study was conducted in two phases. The first consisted
      in collecting antibiotics prescriptions. In a second phase, the prescriptions
      were submitted to 4 experts who assessed the correctness of the prescribing. Out
      of the 588 prescriptions that could be analysed, 173 (29.4%) were correct The
      quality of the prescribing seems to depend only on the pathology but not on the
      nature of the basic training of the prescriber

PMID- 19583035
TI  - [Assessing the reliability of clinical malaria diagnosis in children consulting
      in three peripheral health care facilities, in Niakhar rural area, Senegal].
AB  - A demographic survey site has been implemented in Niakhar rural zone in Senegal
      since the 1960s and many epidemiological and demographic studies have been
      conducted in this context. In this Sahelo-Sudanese area, malaria transmission is
      mesoendemic and mainly seasonal. In health care facilities, malaria real burden
      is poorly known as malaria diagnosis only relies on patients' clinical signs. The
      aim of our study was to measure the reliability of malaria diagnosis in these
      health centres by performing a parasitological confirmation of presumptive
      malaria cases and by assessing the validity of diagnosis according to child's
      age. A cross-sectional study was conducted in August-December 2006 (rainy season)
      and in February-June 2007 (dry season) in three health care facilities of the
      area (2 public centres and one private dispensary). Children aged 1 to 14 years
      old and accompanied by an adult were included. Two thick blood smears were
      carried out for each patient. A total of 474 children were included; among them
      208 (43.9%) had a positive blood smear. Among the 335 (70.7%) presumptive malaria
      cases, 182 (54.3%) were confirmed by thick smear. Sensitivity specificity
      positive and negative predictive values were respectively 87.5%, 42.6%, 55.3% and
      80.7%. Clinical signs which were predictive of confirmed malaria were vomiting
      and body temperature > or =38 degrees C. Clinical diagnosis performances
      decreased significantly during the dry season and in children under the age of
      two. The proportion of true malaria cases (54.3%) confirms the results of
      previous studies described in literature and shows a consistency for the last
      twenty years. Malaria is the main diagnosis attributed to patients by health care
      agents, regardless of the child's age or the season, whereas thick smear results
      are predominantly negative among children aged less than 2 and during dry season.
      A better knowledge of malaria morbidity in these health care facilities is an
      asset for setting up further epidemiological studies in this area and
      implementing interventions aiming at improving patients' care.

PMID- 19583036
TI  - [Imported dracunculiasis: four cases confirmed in the south of Algeria].
AB  - The authors report for the first time, in the south of Algeria, four imported
      cases of dracunculiasis in Malian Touaregs. The patients came from Mali. They
      remained two months in Tamanrasset before settling in Illizi where they have been
      working illegally for more than nine months. In August 2007, because of infected
      lesions appearing on their legs a month earlier, the patients decided to go to
      the Illizi hospital for treatment The diagnosis of dracunculiasis was made by
      direct observation of worms emerging from lesions and by microscopic examination
      of larvae. The patients were then isolated and treated. The Ministry of Health
      immediately took measures to avoid local transmission of the disease, never seen
      in the region. The measures consisted in increasing awareness campaign among
      medical and paramedical staff about dracunculiasis and in pointing out the
      importance of detection of new cases among nomadic populations. The risk of
      emergence of a new dracunculiasis indigenous focus in the south of Algeria should
      be seriously considered, especially as the number of immigrants from endemic
      countries is increasing considerably

PMID- 19583037
TI  - The relationship between diabetes mellitus and destructive periodontal disease: a
      meta-analysis.
AB  - PURPOSE: The aim of this study was to systematically review the studies on the
      association between diabetes mellitus (DM) and destructive periodontal disease.
      METHODS: The methods applied include a literature search strategy, inclusion and
      exclusion criteria for selecting the studies, characteristics of the studies,
      quality assessment and meta-analysis. Data sources included PubMed, EMBASE,
      SciELO and LILACS. Selected papers were articles relating to human studies
      investigating whether or not diabetes is a risk factor for periodontitis and if
      it influences the response to periodontal therapy. Those papers that were
      published between January 1980 and June 2007 were retrieved. RESULTS: Of the 2440
      identified studies, 49 cross-sectional and eight longitudinal studies met the
      inclusion criteria. Twenty-seven of the 49 cross-sectional studies that are
      included in this review detected more periodontal disease in diabetic subjects
      compared with non-diabetic subjects. The greater risk of periodontal disease
      progression was associated with type 2 DM, and one study associated DM with
      response to periodontal therapy. Methodological flaws of most of the studies
      included inadequate control for confounders, insufficient statistical analysis
      and lack of information about sampling design. Random effect model showed a
      significant association with clinical attachment level (mean difference = 1.00
      [CI 95% = 0.15 to 1.84]) and periodontal pocket depth (mean difference = 0.46 [CI
      95% = 0.01 to 0.91]) between type 2 diabetics and non-diabetics. CONCLUSIONS:
      Type 2 DM can be considered a risk factor for periodontitis. More studies are
      needed to confirm the harmful effects of type 1 DM on periodontal disease.

PMID- 19583038
TI  - Impacts of toothbrushing frequency on periodontal findings in a group of elderly
      Lithuanians.
AB  - PURPOSE: The aim of this study was to evaluate the severity of the findings of
      dental plaque, calculus and deepened periodontal pockets in relation to self
      reported toothbrushing frequency in a group of elderly Lithuanians. The authors
      hypothesised that those reporting twice daily toothbrushing exhibit less severe
      periodontal findings. MATERIALS AND METHODS: A cross-sectional study of 94
      dentate patients aged 60 or older was conducted at two public dental offices in
      Lithuania. Half-mouth recordings of dental plaque, calculus and deepened
      periodontal pockets were expressed as mean values per subject. These indicators
      described the severity of periodontal findings. A self-administered questionnaire
      provided information on toothbrushing frequency, age, gender and education.
      Statistical evaluation included chi-square test, analysis of variance and
      logistic regression. RESULTS: None of the subjects were plaque-, calculus- or
      pocket-free. Of all, 26% reported that they brushed their teeth at least twice
      daily, 36% once daily and 38% less frequently. Women (P = 0.004), younger (P =
      0.002) and higher educated respondents (P < 0.001) reported twice daily
      toothbrushing more frequently than did their counterparts. Twice daily
      toothbrushing was clearly associated with the least severe conditions regarding
      dental plaque (P = 0.03) and deepened pockets (P < 0.001), but not calculus (P =
      0.39). Logistic regression models revealed higher level of education as the
      strongest factor odds ratio (OR = 2.7; P = 0.04) explaining the lowest scores of
      dental plaque. Higher frequency of toothbrushing was the strongest factor (OR =
      2.1; P = 0.03) to explain the lowest scores of deepened periodontal pockets.
      CONCLUSION: Twice daily toothbrushing contributes to better periodontal health in
      the elderly subjects and should be encouraged at every dental appointment.

PMID- 19583039
TI  - Antimicrobial efficacy of various disinfecting solutions in reducing the
      contamination of the toothbrush -- a comparative study.
AB  - BACKGROUND: Contaminated toothbrushes may play a role in the transmission of
      local or systemic diseases. As modern dentistry emphasises prevention and
      infection control, toothbrushes should be correctly stored, disinfected and
      changed at regular intervals. PURPOSE: The aim of this study was to test the
      efficacy of 3% neem, 2% triclosan, 0.2% chlorhexidine gluconate and 1% sodium
      hypochlorite as toothbrush disinfectants against Streptococcus mutans. MATERIALS
      AND METHODS: This was a double-blind, linear crossover, within-group comparative
      experimental trial conducted among 40 children aged 12 to 15 years. The study was
      divided into five phases: (1) distilled water (control); (2) 3% neem; (3) 2%
      triclosan; (4) 0.2% chlorhexidine gluconate; and (5) 1% sodium hypochlorite. The
      toothbrushes were collected after 5 days of brushing and were soaked for 12 h in
      antimicrobial solutions of separate phases, after which the toothbrushes were
      submitted for microbial analysis to check for the presence of S. mutans. RESULTS:
      The mean colony-forming units (CFUs) of S. mutans at phase 1 when compared with
      baseline was not significant (P = 0.17). The other phases had a significant drop
      in mean CFUs of S. mutans from baseline (P < 0.001). The percentage reduction of
      mean CFUs of S. mutans from baseline was the highest in phase 2 (86%).
      CONCLUSION: It can be concluded that all the solutions are effective in
      toothbrush decontamination, but 3% neem has greater efficacy than other
      solutions.

PMID- 19583040
TI  - Evaluation of different fluoride treatments of initial root carious lesions in
      vivo.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of three topical
      fluoride treatments to arrest initial root carious lesions. MATERIALS AND
      METHODS: Forty patients participated in a randomised study. Of the 60 root
      carious lesions that were included, 20 were randomised for treatment with the
      Carisolv chemo-mechanical technique and the Duraphat (2.23% F) fluoride varnish,
      20 with Duraphat alone and 20 with stannous fluoride solution (8%). The lesions
      were treated at baseline and after three and six months; a clinical evaluation
      was carried out on these occasions and after 1 year. RESULTS: All but four
      lesions were categorised as arrested caries during the 1-year follow-up period:
      18 in the Carisolv/Duraphat group and 19 each in the Duraphat and the stannous
      fluoride groups, respectively. There was a minor reduction in the mean size of
      the lesions of around 0.1 to 0.2 mm height and width and a moderate change in
      colour from a lighter to a darker appearance. No obvious differences were found
      between the groups. The mean percentage of mutans streptococci in plaque from all
      lesions was 3.5% at baseline, and it decreased to 1.8% during the year. The
      decrease was, however, not statistically significant, and no significant
      differences were found between the groups. CONCLUSIONS: It can be concluded that
      the frequent topical application of fluoride could be a successful treatment for
      incipient root carious lesions, irrespective of the type of fluoride treatment
      used.

PMID- 19583041
TI  - Self-control and self-confidence: their relationship to self-rated oral health
      status and behaviours.
AB  - PURPOSE: The aim of this study was to examine the relationship between self
      control and self-confidence, and students' self-rated oral health and oral-health
      related behaviours. MATERIALS AND METHODS: The present study sample consisted of
      178 first-year medical students. The questionnaire that was used in this study
      included information about sociodemographic factors, behavioural factors, self
      reported oral health status, self-control and self-confidence. RESULTS: The
      results showed that mean levels of self-confidence in individuals with current
      extracted teeth and with poor/very poor perceived gingival condition were
      statistically significant and lower than those with no current extracted teeth
      and with self-rated excellent gingival health (P < 0.05). Also participants with
      self-reported gingival bleeding showed lower values of self-control compared with
      those with healthy non-bleeding gingiva (P < 0.05). When oral health behaviour
      was evaluated, it was shown that students with higher scores of self-control were
      more likely to use everyday mouthrinses (P < 0.05). The multiple linear
      regression analyses showed, for self-rated oral and gingival health status as
      dependent variable, a strong association with students' self-confidence level (P
      < 0.05). CONCLUSIONS: The results support the view that self-confidence is
      related with oral health status, and individuals with impaired oral and gingival
      health have a low self-confidence level.

PMID- 19583042
TI  - The oral impact on daily performances and self-reported quality of life in
      elderly people in Florianopolis, Brazil.
AB  - PURPOSE: The aim of this study was to estimate the oral impact on daily
      performances (OIDPs) and its association with self-reported quality of life,
      sociodemographic and oral health conditions, self-reported oral symptoms and
      access to a clinician in elderly people. MATERIALS AND METHODS: A cross-sectional
      study was performed involving individuals over the age of 59 years, resident in
      the city of Florianopolis, Brazil. A sample of 180 individuals selected in a two
      stage approach was examined and interviewed. The World Health Organization
      Quality of Life-BREF (WHOQOL-BREF) was used to collect data on self-reported
      quality of life. The OIDP questionnaire was used to collect data on oral impact
      on daily performances. The criteria for the clinical data were those proposed by
      the World Health Organization. The dependent variable was the oral impact on
      daily performances. The chi-square test was used to examine the association
      between the dependent and the exploratory variables. Variables were inserted in a
      model of multiple logistic regression. The level of significance was set at P <
      0.05. RESULTS: The proportion of individuals who reported oral impact on daily
      performances was 45.6%. The results of the multiple logistic regression analysis
      showed that only the altered condition of the oral mucosa and the social domain
      of the WHOQOL-BREF maintained an independent association with oral impact on
      daily performance. CONCLUSION: Of the investigated elderly individuals 45.6%
      reported oral impact on daily performances. Those who presented altered oral
      mucosa and had a lower performance in the WHOQOL-BREF social domain were more
      likely to report such an impact.

PMID- 19583043
TI  - Oral health-related self-efficacy beliefs and toothbrushing: Finnish and Turkish
      pre-adolescents' and their mothers' responses.
AB  - PURPOSE: The aim of this study was to investigate the association between
      cognitive and behavioural factors of preadolescents and those of their mothers,
      assessed in terms of self-efficacy beliefs and toothbrushing among Turkish and
      Finnish population in the framework of Social Cognitive Theory. The specific
      objective was to test if this possible association worked regardless of cultural
      differences. MATERIALS AND METHODS: Self-administered questionnaires for Finnish
      (n = 338) and Turkish (n = 611) pre-adolescents and their mothers were used to
      collect the information on cognitive (pre-adolescent and maternal self-efficacy)
      and behavioural factors (toothbrushing frequencies). RESULTS: Turkish mothers and
      pre-adolescents reported lower levels of self-efficacy and toothbrushing than did
      their Finnish counterparts (P < 0.005). Finnish pre-adolescents reporting high
      self-efficacy were more likely to have mothers with high levels of self-efficacy
      (OR = 2.14, 95% CI = 1.16 to 3.93), (P = 0.014). Similar positive associations
      emerged between Turkish (OR = 2.45, 95% CI = 1.70 to 3.52), (P = 0.001) and
      Finnish (OR = 6.76, 95% CI = 2.21 to 20.65), (P = 0.001) pre-adolescent self
      efficacy and maternal recommended (twice daily) level of toothbrushing behaviour.
      For pre-adolescents' toothbrushing, their own self-efficacy was the common
      explanatory variable. Binary logistic regression models revealed that the
      maternal toothbrushing accounted for the Turkish pre-adolescents' toothbrushing
      behaviour, whereas maternal self-efficacy did so for the Finnish pre-adolescents'
      (P < 0.001) toothbrushing behaviour. CONCLUSIONS: This study underlines the need
      for integration of pre-adolescent self-efficacy and maternal cognition and
      behaviour into oral health intervention programmes because of their relation to
      recommended toothbrushing behaviour among pre-adolescents, regardless of cultural
      differences. These findings seem to fit with the Social Cognitive Theory, which
      emphasises the significance of cultural factors and cognition as the determinants
      of behaviour.

PMID- 19583044
TI  - Self-reported and clinically-diagnosed dental needs: determining the factors that
      affect subjective assessment.
AB  - PURPOSE: The role of demographic, socioeconomic and psychological factors that
      influence the subjective assessment of dental needs has been the subject of
      contemporary dental research. The aim of this study was to determine the
      relationship between self-reported and clinically diagnosed dental needs, with
      the view of understanding the factors that affect subjective assessments of
      dental problems. MATERIALS AND METHODS: A random sample of 130 subjects, aged 21
      to 63 years, was selected from the non-academic staff members of the Athens
      University of Economics and Business. Data were obtained for 92% (120
      participants) of the sample by a questionnaire-based interview and a clinical
      examination. The questions concentrated on the demographic and socioeconomic
      characteristics and the ratings of oral health, the perceived need, oral
      functional impacts and the level of satisfaction with the appearance. In the
      clinical examination, the oral health status of the participants was thoroughly
      recorded. RESULTS: A strong relationship was detected with the presence of
      caries, badly broken and missing teeth, and self-reported need for care.
      Embarrassment due to one's dental health was also associated with the perceived
      need, although satisfaction with the appearance was not. Neither demographic and
      socioeconomic status nor self-rated oral health was significantly associated with
      a currently perceived dental problem. CONCLUSION: Perceived need for dental care
      is affected by parameters other than demographic and socioeconomic status (i.e.
      parameters that are associated with the presence of symptoms and/or impacts on
      everyday life). Therefore, functional and psychological impacts of the disease
      seem to be as important, if not more, as the clinical indicators while estimating
      the dental needs.

PMID- 19583045
TI  - Self-liking, self-competence, body investment and perfectionism: associations
      with oral health status and oral-health-related behaviours.
AB  - PURPOSE: The aim of this study was to investigate whether self-liking, self
      competence, body investment and perfectionism were associated with self-reported
      oral health status and oral-health-related behaviours. MATERIALS AND METHODS: The
      study sample consisted of 217 first-year dental students. The questionnaire
      included information about sociodemographic factors, behavioural variables, self
      reported oral health status, self-liking, self-competence, body investment and
      perfectionism. RESULTS: Significant differences were found on self-liking, self
      competence and body investment subscales according to several variables:
      perceived dental health, current non-treated caries, current extracted teeth,
      satisfaction by the appearance of own teeth, the last time toothache occurred,
      self-reported gingival condition and self-reported gum bleeding. When oral health
      behaviours were analysed, an association between self-liking, self-competence and
      body investment subscales and flossing, mouthrinse and dental visit pattern was
      revealed. Toothbrushing frequency once a day or less was observed in persons with
      low-levels of self-liking, body care, body protection and perfectionism. Multiple
      linear regression analyses revealed that age, gender, smoking habits, anxiety,
      stress, depression in everyday life, self-liking, self-competence, body image,
      care and protection were positively associated with oral health behaviours.
      CONCLUSIONS: The results suggested that self-liking, self-competence and body
      investment subscales might be the psychosocial risk markers that influence self
      reported oral health status and behaviour.

PMID- 19583046
TI  - Program helps in early identification and treatment of neonatal
      hyperbilirubinemia.

PMID- 19583047
TI  - Great expectations in prenatal care.

PMID- 19583048
TI  - In conversation with Fred Montpetit.

PMID- 19583049
TI  - Waiting to be weighed: a pilot study of the effect of delayed newborn weighing on
      breastfeeding outcomes.
AB  - Although breastfeeding initiation rates are rising in Canada, rates of continued
      breastfeeding remain far below international recommendations. Two factors that
      can have a positive influence on breastfeeding outcomes are maternal confidence
      and support and education provided by public health nurses (PHNs). The weighing
      of newborns by PHNs within the first days after birth is standard practice in
      monitoring neonatal health. However, little is known about the effect of the
      timing of PHN neonatal weighing on maternal confidence or on outcomes such as
      intended duration of breastfeeding and formula supplementation rates. This pilot
      study compared breastfeeding self-efficacy, intended duration of breastfeeding
      and formula supplementation rates in two groups of mothers and newborns randomly
      assigned to different weighing protocols. Newborns in the standard care group
      were weighed post hospital discharge on day 2 or 3 after birth (n = 23), while
      those in the experimental group were weighed on day 5 (n = 26). No statistically
      significant differences were found between the two groups. However, a
      statistically significant increase in formula supplementation over the two-week
      study period was observed in the standard-weighing group and not in the delayed
      weighing group. This finding suggests that further research is needed to assess
      the impact of PHN infant weighing protocols on breastfeeding outcomes.

PMID- 19583050
TI  - Societal abuse in the lives of individuals with mental illness.
AB  - Societal abuse refers to the disadvantages that a group experience as a result of
      unjust social structures. People with mental illness are among the most
      marginalized, oppressed, devalued and stigmatized populations in our society.
      They experience a range of societal abuses, including barriers to health care,
      lack of employment, difficulty accessing and maintaining adequate housing, and
      discrimination. Nurses are in a unique position to address social inequity and
      societal abuse as advocates for health and well-being. The author addresses the
      impact of societal abuse and presents ways in which nurses can advocate for
      people with mental illness.

PMID- 19583051
TI  - Getting on with the job of supporting research.

PMID- 19583052
TI  - Nurse attorney notes precepting the pre-licensure nursing student: some legal
      considerations.

PMID- 19583053
TI  - Family caregivers are unseen patients.

PMID- 19583054
TI  - Perceived support among Iranian mothers of children with learning disability.
AB  - This qualitative phenomenological study explores the lived experiences of
      perceived support by Iranian mothers who have children with learning disability.
      Twelve open interviews with six mothers of learning-disabled children (7-12 years
      of age) were audiotape-recorded with participants' consent. The interviews were
      transcribed and data were analyzed using Van Manen methodology. Two major themes
      emerged from 138 thematic sentences. The mothers'experiences could be interpreted
      as a sense of being in the light or being in the shade of support, with
      variations for different participants. The results indicate a need for more
      specialized and individually adjusted support for mothers in Iran.

PMID- 19583055
TI  - Comparing perceived burden for Korean and American informal caregivers of stroke
      survivors.
AB  - Little is known about the burden of cross-cultural care for stroke patients. This
      article compares the perceived burden for caregivers of stroke survivors in Korea
      and the United States. A brief interview was conducted to determine specific
      problem areas for caregivers. Caregiver burden (using the Sense of Competence
      Questionnaire) and social support (using the ENRICHD Social Support Inventory)
      also were measured. The overall-sense-of-burden-from-caregiving score was
      significantly higher in the Korean cohort than in the American cohort, as was the
      scale regarding satisfaction with the relationship with the recipient of care.
      The primary predictors of overall burden for the combined sample were caregiver
      and patient depression and insufficient social support. Lower perceived social
      support among Korean caregivers was strongly related to caregiver depression,
      while it was more strongly related to increased hours of caregiving in the
      American sample. These findings can help rehabilitation nurses plan supportive
      interventions that incorporate cultural values for stroke survivors and their
      caregivers.

PMID- 19583056
TI  - A stress-busting program for family caregivers.
AB  - Aging baby boomers, longer life spans, and rising levels of Alzheimer's disease
      and related dementias (ADRD) will result in a caregiver crisis in the near
      future. The ways in which caregivers deal with stresses related to caregiving
      will be critical to both their own well-being and their ability to care for
      others. The purpose of this article is to describe the Stress-Busting Program
      (SBP) for family caregivers and its effectiveness. The essential components of
      the SBP are education, stress management, problem solving, and support delivered
      in a group setting for 9 weeks. Results of the SBP indicate that throughout the
      program, caregivers experienced significant improvements in general health,
      vitality, social function, and mental health scores and decreases in anxiety,
      anger/hostility, depression, perceived stress, and caregiver burden. The SBP is a
      cost-effective health-promotion strategy for caregivers who have substantial
      ongoing stress.

PMID- 19583058
TI  - Promoting family integrity to inspire hope in rehabilitation patients: strategies
      to provide evidence-based care.
AB  - The disability of one family member who requires inpatient rehabilitation care
      can negatively affect all family members and ultimately disrupt family integrity.
      The purpose of this article is to demonstrate how promoting family integrity also
      promotes hope when families are confronted with a newly disabled teen or adult.
      Current research findings indicate that rehabilitation nurses are in a key
      position to promote hope and family integrity by facilitating open communication
      between family members, fostering a tone of togetherness within and among
      families, and helping families resolve feelings of guilt and move toward
      forgiveness. These strategies are based on activities from the Nursing
      Interventions Classification (NIC) intervention "Family Integrity Promotion".
      This article presents a review of research to support these NIC activities and
      offers practical suggestions so rehabilitation nurses can incorporate these
      strategies into their daily practice with patients and their family members.

PMID- 19583057
TI  - Predictors of life satisfaction in stroke survivors and spousal caregivers after
      inpatient rehabilitation.
AB  - A global measure of life satisfaction has become increasingly important as an
      adjunctive outcome of healthcare interventions for people with disabilities,
      including those caused by stroke. Life satisfaction of stroke survivors
      mayaffectcaregivingspouses, as well. The purpose of this study was to identify,
      among many physical and psychosocial variables, specific variables that were
      associated with life satisfaction at 12 months after discharge from inpatient
      rehabilitation, and variables that were predictive of life satisfaction 1 year
      later (at 24 months). Between 12 and 24 months, life satisfaction decreased for
      stroke survivors, while it increased for caregiving spouses. The relationship
      between the couple (mutuality) was the only variable that was a significant
      predictor of life satisfaction for both stroke survivors and their spouses.

PMID- 19583059
TI  - Preoxygenation of the morbidly obese with obstructive sleep apnea.

PMID- 19583060
TI  - Anesthetic care of the patient with obstructive sleep apnea.

PMID- 19583061
TI  - Anesthesia and cardiopulmonary bypass for congenital heart surgery.

PMID- 19583062
TI  - Preventing paralytic ileus: can the anesthesiologist help.

PMID- 19583063
TI  - Current perioperative management of the patient with HIV.
AB  - Although modem medical care and current therapies save and prolong the lives of
      many patients with HIV/AIDS, the disease process has no cure and will continue to
      present itself during the perioperative period. All ages, young and old, may
      present with the pathology and, therefore, the anesthesiologist must have sound
      knowledge of the disease, treatment, complications, and multiorgan
      manifestations. It will be necessary to review the current treatment modalities
      for HIV as pharmacologic strategies are ever evolving with this disease process.

PMID- 19583064
TI  - A proposed classification of simulators.
AB  - This paper provides a coherent and comprehensive classification of simulators,
      using a five letter coding system, and is based on the characteristics of the
      user interface and the logic controller.

PMID- 19583065
TI  - Modern strategies for the anesthetic management of the patient with diabetes.
AB  - Diabetes Mellitus (DM) is an endocrine disease with high incidence. Long-term
      complications involve the eyes, kidneys, nerves, and blood vessels, resulting in
      hypertension, cardiac ischemia, atherosclerosis, and renal failure, among other
      syndromes. Given this prevalence, anesthesiologists, especially those who work
      with older patients, may expect to encounter some aspect of diabetes almost every
      day. Appropriate preoperative evaluation and rational intraoperative and
      postoperative management of this complex disease in elective and emergency
      circumstances are essential. Recent studies have emphasized the need to maintain
      tight perioperative glycemic control and new guidelines have been presented.

PMID- 19583066
TI  - The impact of intraoperative transoesophageal echocardiography on decision-making
      during cardiac surgery.
AB  - BACKGROUND: Real time intraoperative transoesophageal echocardiograpgy (TOE) has
      an expanding role in peri-operative management and surgical decision making.
      OBJECTIVES: Studies of the effect of transoesophageal echocardiography (TOE) on
      intraoperative decision making commonly emphasise major changes in operative
      plans. We examined more subtle effects using a novel scale, recording influences
      on management as follows: Level 1: TOE had no effect on management, confirmed and
      quantified known pathology. Level 2: TOE altered hemodynamic and/or anesthetic
      management. Level 3: TOE evaluated the adequacy of surgical intervention/or
      repair. Level 4: TOE led to an alteration in the surgical plan. We compared the
      impact of TOE as an aid to intra-operative management in coronary artery bypass
      cases with other types of cardiac surgery. METHODS: Retrospective, observational
      study in a single centre, university-affiliated hospital included 319 patients
      undergoing cardiac surgery and suitable for TOE. TOE was performed in each
      patient before and after the institution of cardiopulmonary by-pass. Normal and
      abnormal echocardiographic findings as well as immediate outcomes of the surgical
      procedure were recorded using a standard database form. Instances where TOE lead
      to alteration in operative management were documented. The findings were also
      compared with those documented on preoperative echocardiography. RESULTS: In 141
      CABG patients TOE had a level 1 impact in 73%, level 2 impact in 11.6%, levels 3
      and 4 in 7% and 7.8% respectively. In 178 non CABG patients these values were 2%,
      1.6%, (p < 0.05), 72.4% (p < 0.05) and 23.6% (p < 0.05) respectively. CONCLUSION:
      The impact of TOE in CABG procedures, while significantly less than that in non
      CABG surgical procedures, remains substantial.

PMID- 19583067
TI  - Effects of sevoflurane on postoperative liver functions in morbidly obese as
      compared to the non-obese patients.
AB  - OBJECTIVE: To assess the effect of sevoflurane anesthesia on hepatic function in
      morbidly obese versus non-obese patients undergoing abdominal surgeries. METHODS:
      We prospectively evaluated the levels of the serum concentration of liver enzymes
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate
      dehydrogenase (LDH), gamma glutamyl transferase (GGT), alkaline phosphatase
      (ALP), and total bilirubin (TBil), in 42 morbidly obese and 40 non obese patients
      who were scheduled for elective abdominal surgery under sevoflurane anesthesia at
      the Jordan University Hospital, Amman, Jordan. Measurement of liver enzymes was
      done in the recovery room, and on the first, 3 and 7 days after sevoflurane
      anesthesia, and the results were compared between the morbidly obese and non
      obese patients. RESULTS: ALT, AST, GGT and LDH increased significantly in the
      morbidly obese than they did in non obese patients. In morbidly obese patients
      TBil increased gradually peaking 7 days after anesthesia, LDH increased in the
      recovery room, AST and ALT increased in the recovery room and first day, while
      GGT increased 7th day after anesthesia. In non obese patients, AST, LDH increased
      in the recovery. ALP did not change in both groups. CONCLUSION: Sevoflurane
      induces elevation of the serum liver enzymes in morbidly obese patients with
      variable onsets.

PMID- 19583069
TI  - Evaluation of a blood conservation strategy in the intensive care unit: a
      prospective, randomised study.
AB  - OBJECTIVE AND METHODS: Anemia is a common problem in the ICU population. Most
      patients are anemic at admission, their hemoglobin concentrations declining
      further thereafter. The aim of the present study was to evaluate the effect of a
      combination strategy, involving closed arterial blood gas sampling and the use of
      pediatric vials for phlebotomy (Group A), on the sampling-induced blood loss and
      the rate of decline in hemoglobin in adult ICU patients. Combination (Group A)
      was compared to the current standard technique of arterial line sampling and
      adult vial phlebotomy (Group B) in a prospective, randomised, ethically-approved
      trial for the first 72 hours of their ICU stay. Peri-operative, oncology,
      coagulopathic and uremic patients were excluded. All other ICU patients with
      arterial cannulae and predicted to stay beyond 3 days, were enrolled. RESULTS: 39
      patients entered the study, 20 in Group A, and 19 in Group B. Data collection was
      complete for all. There was a statistically significant difference in sampling
      induced blood loss between the groups over the first 72 hours of treatment (mean
      +/- standard deviation: 15.16 +/- 5.3 ml Group A vs 45.11 +/- 14 ml Group B,
      p<0.001). There was a smaller decline in mean hemoglobin level, which was not
      statistically significant (0.79 +/- 0.6 g/dL vs 1.30 +/- 1.13, p = 0.09).
      CONCLUSIONS: Overall, this strategy reduced measurable blood losses from
      phlebotomy. In larger trials it might also preserve hemoglobin levels.

PMID- 19583068
TI  - Patient survey of continuous interscalene analgesia at home after shoulder
      surgery.
AB  - BACKGROUND: The use of continuous peripheral nerve blocks at home (CPNBH) has
      improved patients' perioperative experience. In 30 months, 348 patients were sent
      home with interscalene CPNBH. METHODS: With the Institutional Review Board (IRB)
      approval, all patients were surveyed for quality of analgesia and complications.
      The patients and their caretaker received verbal and written instructions,
      including care of the catheter and pump, and a list of complications and side
      effects. All were instructed on catheter removal and were given a contact number,
      and patients were called once per day. RESULTS: 172 patients responded to this
      survey. The majority of patients (76%) had very good postoperative analgesia.
      There was a 9.3% incidence of leakage of clear fluid, a 5.8% incidence of
      premature dislodgement, and an 8.7% incidence of shortness of breath. Residual
      neurological symptoms persisted in 18.6% of responders, all resolving within two
      months except in one case. A large proportion (40%) required no oral analgesics,
      and half of the rest required less than 3 pain pills. Most (94.1%) felt
      comfortable removing the catheters at home by themselves or by a family
      member/caretaker. CONCLUSION: This survey shows that CPNBH results in low pain
      scores and a low incidence of side effects. Many patients commented positively on
      their overall impression of their anesthesia care, particularly the level of
      attention that they received. This highlights the low incidence of those
      complications and neural injury.

PMID- 19583070
TI  - Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia.
AB  - BACKGROUND: The prolongation of spinal anesthesia by using clonidine through the
      oral, intravenous and spinal route has been known. The new alpha 2 agonist,
      dexmedetomidine has been proved to prolong the spinal anesthesia through the
      intrathecal route. We hypothesized that dexmedetomidine when administered
      intravenously following spinal block, also prolongs spinal analgesia. METHODS: 48
      patients were randomly allocated into two equal groups following receiving spinal
      isobaric bupivacaine 12.5 mg. Patients in group D received intravenously a
      loading dose of 1 microg/kg dexmedetomidine over 10 min and a maintenance dose of
      0.5 microg/kg/hr. Patients in group C (the control group) received normal saline.
      The regression times to reach S1 sensory level and Bromage 0 motor scale,
      hemodynamic changes and the level of sedation were recorded. RESULTS: The
      duration of sensory block was longer in intravenous dexmedetomidine group
      compared with control group (261.5 +/- 34.8 min versus 165.2 +/- 31.5 min, P <
      0.05). The duration of motor block was longer in dexmedetomidine group than
      control group (199 +/- 42.8 min versus 138.4 +/- 31.3 min, P < 0.05). CONCLUSION:
      Intravenous dexmedetomidine administration prolonged the sensory and motor blocks
      of bupivacaine spinal analgesia with good sedation effect and hemodynamic
      stability.

PMID- 19583071
TI  - Attenuation of hemodynamic responses following laryngoscopy and tracheal
      intubation -- comparative assessment of clonidine and gabapentin premedication.
AB  - OBJECTIVE: The present study was conducted to compare the effect of clonidine and
      gabapentin premedication in modifying the hyperdynamic response following
      laryngoscopy and tracheal intubation. METHODS AND MATERIALS: Seventy-five ASA I
      II patients of both sexes (37 males (49.3%), 38 females (50.7%)) 18 to 45 years
      (mean 32.8 +/- 8.65 yr.) were randomly allocated into three equal groups (25
      each). Group-1 received 0.2 mg clonidine, Group-2 received placebo and Group-3
      received 900 mg gabapentin, 120 minute before operation. Heart rate, systolic,
      diastolic and mean arterial blood pressure were measured before induction of
      anesthesia, before laryngoscopy, and 1, 3, 5, 10 min after intubation. RESULTS:
      Analysis revealed that the heart rate, systolic, diastolic and mean arterial
      blood pressure significantly differed between groups (p<0.001, p = 0.003,
      p<0.001, p<0.001, respectively). The highest rates of heart rate, systolic,
      diastolic and mean arterial blood pressure were in the placebo group and in one
      minute after laryngoscopy, and the lowest rate were in the gabapentin group at
      the time of 1, 3, 5 and 10 after laryngoscopy, except that the lowest rate of
      heart rate in 10 min after laryngoscopy was in clonidine group. CONCLUSION: The
      data propose that both clonidine and gabapentin have effective role in blunting
      hyperdynamic responses after laryngoscopy, more so with gabapentin.

PMID- 19583072
TI  - Pediatric cancer pain management at a regional cancer center: implementation of
      WHO Analgesic Ladder.
AB  - PURPOSE: To collect data on the prevalence of various types of cancer pain in a
      sample of children with cancer, and to implement the WHO Analgesic Ladder in the
      management of pain in pediatric cancer. METHODS: Eighty four pediatric patients
      suffering of cancer pain were studied during the period 2001-2006. Patients were
      requested to rate their global intensity of pain on 0-100 mm visual analogue
      scale (VAS 0 = no pain, 100 = maximum pain). Pain management was performed in
      accordance with the WHO Analgesic Ladder for cancer pain. Patients were followed
      up weekly for three weeks. RESULTS: Of the 84 pediatric children with cancer,
      pain was nociceptive in 26 (31%), neuropathic in 12 (14.3%) and mixed in 46
      (54.8%). Almost 7 (8.3%) of patients were on WHO step 3 at baseline. Thereafter
      the WHO step 3 increased; first week visit 36 (43%) patients; second week visit
      58 (69%), and third week 69 (82.1%). At baseline, 40 (47.6%) patients took NSAID
      only, 2 (2.4%) patients took adjuvant, while 38 (45.2 %) patients took
      combination of NSAID and adjuvant treatment. There was statistically significant
      (p = 0.000) reduction in VAS as time progressed. CONCLUSION: Cancer pain in
      pediatric age group can be well managed in accordance with the WHO Analgesic
      Ladder. Aggressive symptoms and control of treatment of related side effect are
      also needed to ensure successful implementation and the WHO Analgesic Ladder.

PMID- 19583073
TI  - The prophylactic effect of rectal acetaminophen on postoperative pain and opioid
      requirements after adenotonsillectomy in children.
AB  - BACKGROUND: Postoperative pain in children is common after adenotonsillectomy.
      Rectal acetaminophen has been used effectively for postoperative pain management
      in small children. The aim of this randomized double blind study was to evaluate
      the prophylactic effect of rectal acetaminophen on postoperative pain management
      and opioid requirements in children undergoing adenotonsillectomy. MATERIALS AND
      METHODS: 104 children, 7 to 15 yr, ASA I or II scheduled for elective
      adenotonsillectomy were recruited for the study. Patients were randomized to
      receive either rectal acetaminophen 40 mg/kg or nothing after induction of
      standard anesthesia. The postoperative pain was assessed using visual analog
      scale (VAS) every 2 hours for the first 6 hours. The need for rescue analgesic,
      intravenous pethedine of 0.5 mg/kg, was recorded at 24 hours after surgery.
      RESULTS: Pain scores were significantly lower in acetaminophen group at different
      times (p<0.001) and needed less rescue analgesic (p<0.001). CONCLUSION: We
      conclude that prophylactic rectal acetaminophen is effective in reducing pain
      after adenotonsillectomy and postoperative analgesic requirement.

PMID- 19583074
TI  - Pregnancy at term does not alter the responses to a mechanical and an electrical
      stimulus after skin EMLA application.
AB  - BACKGROUND: Pregnancy is associated with reduced local anesthetic requirements
      and increased pain thresholds, possibly due to hormonal changes and activation of
      endogenous opioids. METHODS: We compared the responses to a mechanical and an
      electrical stimulus in 30 pregnant women (pregnant group) scheduled for cesarean
      section and 30 healthy female volunteers (control group) matched for age. Pain
      was assessed by Visual Analogue Scale (VAS) on two different days after skin
      application of EMLA or placebo cream on the forearms. EMLA and placebo cream were
      randomly applied on the medial surface of both forearms for 30 min in a blind
      cross over manner and the subjects received a mechanical stimulus generated
      through a pressor palpator followed by an electrical stimulus generated through a
      nerve stimulator. RESULTS: Average VAS values from both trials did not differ
      between pregnant and control group exposed to the mechanical or electrical
      stimulus after EMLA application or after mechanical or electrical stimulus after
      placebo cream application.. CONCLUSIONS: Late pregnancy is not associated with
      increased sensitivity to local anesthetics (EMLA) applied to the skin, under our
      study conditions.

PMID- 19583075
TI  - Robotic laparoscopic radical cystectomy inhalational versus total intravenous
      anesthesia: a pilot study.
AB  - BACKGROUND: Robotic assistance may refine laparoscopic radical cystectomy. Steep
      Trendelenburg tilt (TT) and pneumoperitoneum (PP) are challenging anesthesia
      maneuvers. In view of those maneuvers, would inhalational anesthesia or total
      intravenous anesthesia (TIVA) be the more appropriate anesthetic management for
      this kind of surgery? This issue is under consideration in this clinical trial.
      METHODS: 15 patients scheduled for robotic laparoscopic radical cystectomy (RLRC)
      were randomly allocated into two groups to be anesthetized by either isoflurane
      anesthesia (ISO n = 8) or ketamine-midazolam-fentanyl total intravenous
      anesthesia (TIVA n = 7). The hemo-respiratory dynamics, oxygenation and
      biochemical variables were monitored taking into consideration the system organ
      function as primary outcomes, and operative conditions and recovery profile as
      secondary outcomes. RESULTS: The PP and TT increased the mean arterial and airway
      pressures and decreased lung compliance, and were associated with respiratory
      acidemia, while changes in heart rate remained within normal range. The duration
      of PP was shorter in TIVA patients but mean arterial pressure was higher than ISO
      group. ISO was associated with increased plasma concentrations ofprothrombin,
      fibrinogen and aspartate aminotransferase. CONCLUSIONS: Though the number of
      patients is small in this study (n = 15), it nevertheless brings to light the
      advantages of TIVA during the robotic laparoscopic radical cystectomy (RLRC), by
      shortening the duration of PP without an increase in prothrombin and fibrinogen
      concentrations. A lager number of clinical trial are needed to further clarify
      this issue.

PMID- 19583076
TI  - The effect of nitroglycerin as an adjuvant to lidocaine in intravenous regional
      anesthesia.
AB  - PURPOSE: The disadvantages of intravenous regional anesthesia (IVRA) include slow
      onset, poor muscle relaxation, tourniquet pain, and rapid onset of pain after
      tourniquet deflation. In this randomized, double-blind study, we evaluated the
      effect of nitroglycerin (NTG) in quality improvement when added to lidocaine in
      IVRA. METHODS: Forty-six patients (20-50 yrs), were randomly allocated in two
      equal groups. Under identical condition, the control group received a total dose
      of 3 mg/kg of lidocaine 1% diluted with saline, and the study group received an
      additional 200 microg NTG. Vital signs and tourniquet pain, based on visual
      analog scale (VAS) score were measured and recorded before and 5, 10, 15, 20, and
      30 min after anesthetic solution administration. The onset times of sensory and
      motor block were measured and recorded in all patients. After the tourniquet
      deflation, at 30 min and 2, 4, 6, 12 and 24 h, VAS score, time to first analgesic
      requirement, total analgesic consumption in the first 24 h after operation, and
      side effects were noted. RESULTS: The sensory and motor block onset time were
      shortened in study group (2.61 vs. 5.09 and 4.22 vs. 7.04 min, respectively) (p <
      0.05). The recovery time of sensory and motor block and onset of tourniquet pain
      were also prolonged (7.26 vs. 3.43, 9.70 vs. 3.74 and 25 vs. 16.65 min.,
      respectively) (p < 0.05). Analgesia time after tourniquet deflation was prolonged
      and tourniquet pain intensity was lowered in study group (p < 0.05).
      Intraoperative fentanyl and meperedine requirement during first postoperative day
      and pain intensity at 4, 6, 12 and 24 hr postoperatively were lower in the study
      group (p < 0.05). There were no significant side effects. CONCLUSION: The NTG
      adding to lidocaine in intravenous regional anesthesia shortens onset times of
      sensory and motor block and decreases the tourniquet and postoperative pain,
      without any side effect.

PMID- 19583077
TI  - Evaluation of the tourniquet leak during forearm intravenous regional anesthesia 
      - manual vs automatic pump injection.
AB  - BACKGROUND: The present study was conducted to compare the effect of pump
      injection versus manual injection on the venous pressure, during forearm
      intravenous regional anesthesia (IVRA) and the incidence and the magnitude of
      lidocaine leak. METHODS: A crossover randomized study of IVRA with a forearm
      tourniquet was conducted on 14 male healthy volunteers. This study was performed,
      once using manual injection of local anesthetic and once using automatic pump
      injection, on two separate sessions. In both techniques, 0.3 ml/kg lidocaine 0.5%
      was injected over 90 seconds. The occlusion pressure, continuous venous pressure
      and the serum lidocaine two minutes at end of injection, were recorded. RESULTS:
      The mean occlusion pressure 161.6 (17.2) mmHg was always higher than the mean
      initial arm systolic blood pressure 131.7. The maximum venous pressure was
      significantly higher in the manual technique 176.7 (15.4) mmHg than in the pump
      technique 161.3 (12.3) mmHg (p = 0.04). The incidence of lidocaine leak was
      significantly lower (35.71%) in the pump technique compared to (78.5%) in the
      manual technique (p = 0.02). Moreover; the mean lidocaine plasma concentrations
      was significantly higher [0.86 (0.5) microg x ml(-1)] in the manual technique
      compared to [0.32 (0.4) microg x ml(-1)] the pump technique (p = 0.04).
      CONCLUSION: The use of pump injection for forearm IVRA could significantly
      decrease the maximum venous pressure, and decrease the incidence and the
      magnitude of lidocaine leak past the tourniquet.

PMID- 19583079
TI  - Anesthetic implications of acute methylenedioxymethamphetamine intoxication in a
      patient with traumatic intracerebral hemorrhage.
AB  - The use of the street drug methylenedioxymethamphetamine (MDMA), commonly
      referred to as ecstasy, has become increasingly prevalent amongst teenagers and
      young adults in the United States and many other parts of the world. While most
      anesthesiologists are facile with the intricacies of managing patients
      intoxicated by alcohol, cocaine and narcotics the new "club" drugs present a
      challenge, especially under emergency conditions. MDMA, in particular, is the
      most commonly abused club drug and potentially one of the most dangerous in the
      perioperative period. We present a case report of traumatic subarachnoid
      hemorrhage in a patient with acute MDMA intoxication and a review of the
      anesthetic implications.

PMID- 19583080
TI  - Human poisoning after ingestion of puffer fish caught from Mediterranean Sea.
AB  - Puffer fish poisoning is due to a powerful neurotoxin produced by bacteria living
      in this kind of fish. Though the sea of Lebanon (Mediterranean) is not endemic of
      puffer fish and incidence of its serious poisoning is rare, yet occasional
      incidences do occur. The purpose of this presentation is to raise the awareness
      of fishermen, fish-restaurant frequenters, public health organizations and the
      Ministry of Health, of its serious symptomology and to seek medical help as soon
      as possible.

PMID- 19583078
TI  - Time to extubation in infants undergoing pyloromyotomy -- isoflurane inhalation
      vs remifentanil infusion.
AB  - BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) associated with
      metabolic alkalosis, could induce late anesthesia recovery, especially when
      opioids are used. The aim of this study was to compare the time of extubation and
      the quality of perioperative analgesia in infants scheduled for pyloromyotomy,
      receiving either isoflurane inhalation or remifentanil infusion. METHODS: Thirty
      full-term infants scheduled for pyloromyotomy were prospectively studied. A
      standardized anesthetic induction was performed. For maintenance of anesthesia,
      infants were randomly allocated to receive either isoflurane 0.75% of inspired
      concentration (GI n = 15), or remifentanil as a continuous infusion of 0.4 microg
      x kg(-1) x mn(-1) (GR n = 15). At the beginning of skin closure, the anesthetic
      was discontinued and 15 mg x kg(-1) of paracetamol administered. Non parametric
      tests were used in statistical analysis. RESULTS: The time to extubation was
      similar in both groups. The intraoperative heart rate was significantly lower in
      the GR group. CONCLUSION: Remifentanil provided better intraoperative analgesia
      than isoflurane in infants undergoing pyloromyotomy without increasing time to
      extubation.

PMID- 19583081
TI  - Failure of endtidal carbon dioxide to confirm tracheal intubation in a neonate
      with a single ventricle and severe pulmonary stenosis.

PMID- 19583082
TI  - Uneventful epidural analgesia in a patient with severe thrombocytopenia.
AB  - Epidural analgesia is the most effective method for analgesia in labor. It has,
      however, contraindications and carries many serious side effects. Though
      coagulopathy is an absolute contraindication for epidural and axial blocks, yet
      there are no absolute limits for platelet counts that stand in the way of
      providing epidural analgesia. In a patient who is writhing in pain due to severe
      uterine contractions, and in whom there exists a recent normal platelet screening
      and no history of bleeding disorders, it is internationally acceptable between
      anesthetists to provide epidural analgesia without waiting for a new platelet
      screening.

PMID- 19583083
TI  - The rate dependent bundle branch block -- transition from left bundle branch
      block to intraoperative normal sinus rhythm.
AB  - A chronic hypertensive patient with electrocardiogram (ECG) showing left bundle
      branch block (LBBB) was given general anesthesia for right modified radical
      mastectomy. Her ECG reverted to normal sinus rhythm intermittently during peri
      operative period. This intermittent rate-dependent LBBB is a rare entity. Though
      hypertension is one significant co-morbid condition, the risk evalution of LBBB
      during anesthesia only on an ECG finding, is not justifiable. Rather patient
      should be investigated further for any cardiac risk.

PMID- 19583084
TI  - Intubation-induced tracheal stenosis -- the urgent need for permanent solution.
AB  - The most common site for the occurrence of intubation-induced tracheal damage is
      at the area in contact with the inflatable cuff. After the change from high
      pressure to low-pressure cuffs, major tracheal lesions still continue to occur.
      This is a case of tracheal stenosis that occurred after 7 days of intubation with
      standard cuffed tube whose cuff pressure was assessed by subjective means. Three
      weeks later, patient was in need of reintubation, the trachea was found to be
      stenotic at the site of the previous tube cuff. Emergency tracheostomy had to be
      performed and computed axial tomography (CT) confirmed the tracheal stenosis. A
      month later, the patient had another cardiac arrest from which he did not
      recover. Our message in this report is to throw light and alert clinicians
      involved in tracheal intubation, of the presence of the Lanz endotracheal tube
      whose pilot balloon is designed to automatically regulate the intra-cuff pressure
      and thus prevent the occurrence of tracheal stenosis due to high pressure. We
      strongly recommend the presence of Lanz tracheal tubes as standard emergency
      equipment in intensive care settings and in any situation in which cuff pressure
      is likely to increase.

PMID- 19583085
TI  - Obstruction of endotracheal tube; a manufacturing error.

PMID- 19583086
TI  - Tracheal cartilage fracture with the percutaneous dilatational tracheostomy,
      Ciaglia method.

PMID- 19583088
TI  - Anesthesia for Nelson's syndrome.

PMID- 19583087
TI  - Ventriculo-peritoneal shunt surgery in an infant with double aortic arch, patent
      ductus arteriosus and atrial septal defect.
AB  - Double aortic arch with patent ductus arteriosus and atrial septal defect is an
      uncommon association. Such complex cardiac lesions may complicate an otherwise
      normal anesthetic course. We came across a case with aqueductal stenosis and
      hydrocephalus, scheduled for ventriculo-peritoneal shunt surgery, on an emergent
      basis. The child was managed successfully. The anesthetic implications of
      resultant left-to-right shunt with increased intracranial pressure have been
      described.

PMID- 19583089
TI  - Sudden cardiac arrest during cesarean section -- a possible case of amniotic
      fluid embolism.
AB  - Amniotic Fluid Embolism (AFE) is a rare obstetric catastrophe that occurs in
      approximately 1/50,000 pregnancies and has a mortality rate in excess of 80%. AFE
      is a condition that is poorly understood and often difficult to diagnose. We
      report a case of a healthy 27-yr-old gravid two, 35 wk gestation parturient with
      a previous Cesarean section two years previously, and presently admitted for
      emergent Cesarean section due to premature uterine contractions. Induction of
      general anesthesias was performed with no problem and a male preterm infant with
      Apgar 8 at 1 min was delivered. Amniotic fluid was bloody and 40% placental
      abruption existed. Following delivery of the placenta, patient suddenly became
      plethoric and O2 saturation began to decrease and no pulse could be palpated!
      Immediate CPR was successful but she was hemodynamically unstable and signs of
      right heart strain was obvious. Right jugular venous catheterization was
      performed, vasopressors were administered. After a two hours period of relatively
      stable vital signs, patient's reflexes returned to normal, however, profound
      coagulopathy on lab data was reported and she was treated with 10 unit Packed Red
      Blood Cells (PRBCs), 10 unit FFP and 8 unit platelets, Sodium bicarbonate,
      oxytocin and Methergine. The patient remained hemodynamically unstable while
      laparotomy-hysterectomy was performed to stop the bleeding. Unfortunately
      attempts were unsuccessful and patient died four hours later in ICU. Post-mortem
      findings showed signs of Disseminated Intravascular Coagulation (DIC), no fetal
      squamous cells in pulmonary vasculature were found and special staining of
      Cytokeratin marker shows no positive cells in lumen of vessels. The post-mortem
      diagnosis of AFE is challenging to forensic investigators and pathologists and
      can be confirmed by histological confirmation of amniotic fluid contents in the
      pulmonary vasculature, although they may be difficult to identify. In recent
      years it has been suggested that AFE is an anaphylactoid reaction to fetal
      antigens and an elevated serum tryptase level is increasingly being used to
      support the diagnosis. Sudden onset of cardiovascular collapse and early signs of
      right heart strain and fulminant DIC supports the diagnosis of AFE in this case,
      although no fetal debri could be find in pathologic staining.

PMID- 19583090
TI  - Perioperative care of a child with Ullrich congenital muscular dystrophy.
AB  - Ullrich congential muscular dystrophy (UCMD) is a severe form of congenital
      muscular dystrophy manifesting axial muscle contractures and distal joint
      hyperlaxity. Severe hypotonia and associated respiratory failure may occur early
      in the disease process. Given the various associated orthopedic conditions,
      anesthetic management may be required during surgical interventions to correct
      skeletal deformities or these patients may present with surgical conditions
      unrelated to their primary illness. We present a 4-year-old with UCMD who
      required operative intervention for a ruptured appendix. Anesthetic care
      implications included the need for a rapid airway control to limit the risks of
      aspiration due to the intra-abdominal process, choice of neuromuscular blocking
      agent for rapid sequence intubation, associated airway issues related to
      micrognathia and limited mouth opening, and the potential for involvement of the
      cardiovascular and respiratory systems. The perioperative management of patients
      with UCMD is discussed including the use of propofol and remifentanil for rapid
      sequence intubation to avoid the need for neuromuscular blocking agents.

PMID- 19583091
TI  - Practice guidelines and prevention of obstetric anesthesia-related maternal
      mortality.

PMID- 19583092
TI  - Tongue swelling in a child after cleft palate surgery.

PMID- 19583093
TI  - Transmission of HIV from parent to child in Papua New Guinea.

PMID- 19583094
TI  - The epidemiology of malaria in the Papua New Guinea highlands: 5. Aseki, Menyamya
      and Wau-Bulolo, Morobe Province.
AB  - Although not strictly a highlands province, Morobe encompasses large highlands
      areas, the most important being Aseki, Menyamya and Wau-Bulolo. A series of rapid
      malaria surveys conducted in both the wet and dry seasons found malaria to be
      clearly endemic in areas below 1400 m in Menyamya and Wau-Bulolo, with overall
      prevalence rates in the wet season (25.5%, range: 9.1%-39.2%) greatly exceeding
      those in the dry season (8.3%, range: 2.4%-22.8%; p < 0.001). In the wet season
      surveys Plasmodium falciparum was the clearly predominant species, accounting for
      63% of all infections. P. vivax increased in frequency in the dry season (from
      27% to 46%, p < 0.001), while P. falciparum and P. malariae decreased. In line
      with past surveys a low prevalence of malaria was found in the Aseki area.
      Malaria was found to be the main source of febrile illness in the wet season with
      at least 60% of measured or reported fever associated with parasitaemia. Other
      causes of febrile illness dominated in the dry. In villages with parasite
      prevalence rates < 20% mean haemoglobin levels and prevalence of severe anaemia
      were strongly correlated with overall parasite prevalence. In addition concurrent
      malarial infections were associated with a strong reduction of individual
      haemoglobin levels (-1.2 g/dl) and there was increased risk of moderate-to-severe
      anaemia with concurrent malaria. Malarial infections are thus the most
      significant cause of febrile illness and anaemia in the highlands fringe
      populations in Morobe. As a consequence all villages below 1500-1600 m in Morobe
      Province should be included in malaria control activities.

PMID- 19583095
TI  - The epidemiology of malaria in the Papua New Guinea highlands: 6. Simbai and
      Bundi, Madang Province.
AB  - Although predominantly a lowland province, Madang also includes highland areas
      such as Simbai and Bundi along the northern highland fringe. While the malaria
      situation in the coastal lowlands has been studied in great detail, the current
      malaria situation in the highland fringe communities has not been studied in
      depth since the 1960s. A series of recent malariological surveys found that the
      malaria situation has changed little over the last 40 years in both Simbai and
      Bundi. In the Simbai area there is little malaria transmission in villages above
      1400 m, with a prevalence rate (PR) of 2.5-4.2%. Below 1400 m, however, there is
      moderate to high transmission (PR 8.6-24.7%) with surprisingly little difference
      in prevalence rates between survey villages, despite large differences in
      altitude. Prevalence rates of malaria infection were low in all Bundi villages
      (2.5-8.5%) with most infections occurring in adolescents and adults, which
      indicates limited acquisition of effective immunity to malaria and the
      possibility that many infections are acquired when travelling to the highly
      malarious lowlands area. Based on spleen rates the lower Simbai area would be
      regarded as mesoendemic, and the upper Simbai and Bundi areas as hypoendemic.
      Only in the lower Simbai area is malaria a major cause of febrile illness.
      However, in all areas village mean haemoglobin (Hb) levels were highly correlated
      with the prevalence of malaria infections, while concurrent parasitaemia reduced
      individual Hb levels by 1.3 g/dl (CI95 [1.0-1.5], p < 0.001) and significantly
      increased the risk for moderate-to-severe anaemia (Hb < 8 g/dl) (adjusted odds
      ratio 5.6, CI95 [3.6-8.6], p < 0.001). Based on the survey results, areas of
      different malaria epidemiology are delineated and options for control in each
      area are discussed.

PMID- 19583097
TI  - Urinary tract infection in infants and young children presenting with fever
      without a focus in Port Moresby.
AB  - A prospective study was undertaken to document the importance of urinary tract
      infection (UTI) as a cause of fever without a focus (FWF) in children less than 3
      years of age presenting to the Children's Outpatients Department (COPD) of Port
      Moresby General Hospital (PMGH). 98 children, 55 males and 43 females, with a
      median age of 17 months and an interquartile range of 5-31.25 months, were
      recruited. In addition to a history and physical examination each child had a
      full blood count, a malaria parasite smear, and a urine sample (obtained by clean
      catch or midstream methods) for dipstick testing, microscopy and culture. Blood
      culture was performed where practicable. Lumbar puncture and cerebrospinal fluid
      (CSF) examination were done only if clinically indicated. UTI was diagnosed on
      urine culture in 9 of the 98 children. Both urinary nitrite and leukocyte
      esterase tests were sensitive (89%) and specific (96%). Other causes of FWF were
      classified as non-specific viral infection (31 children), lower respiratory tract
      infection (11), malaria (7), meningitis (4), bacteraemia (1 neonate) and other or
      unknown causes. The finding of UTI in 9% of the children is consistent with data
      from other tropical countries. Checking for urinary tract infection, which can be
      done using noninvasive methods of urine collection, is an important part of the
      investigation of infants and children with FWF.

PMID- 19583096
TI  - Chlamydia trachomatis infection and distribution of serovars in the Eastern
      Highlands Province, Papua New Guinea.
AB  - We have used nested polymerase chain reaction (PCR) and the PCR-based
      endonuclease digestion method to genotype Chlamydia trachomatis serovars in 460
      infected individuals from the Eastern Highlands Province of Papua New Guinea. Our
      study groups comprised women who presented in labour to the Goroka Base Hospital,
      their newborn infants, symptomatic children who presented to the hospital's
      Outpatients Department and men and women from 15 randomly selected villages in
      the Asaro Valley. In this analysis, the major outer membrane protein (MOMP) gene,
      omp1, of C. trachomatis was amplified using DNA obtained from the endocervix of
      women, urine from men, and both the eye and nasopharynx of children. Amplified
      DNAs were digested concurrently using Alul and a combination of EcoRI, Hinl and
      Hpall restriction enzymes. The mixtures were separated on electrophoretic gels
      and the respective serovars designated on the basis of resolved digested DNA
      patterns. Our results, which were confirmed also by omp1 sequence data, show
      serovars D, E, F, G, H and L3 to be present in the studied communities. The
      overall relative frequencies of these serovars were 30%, 21%, 25%, 1%, 20% and 2%
      respectively, with serovars D, E, F and H accounting for 97% of these infections.
      Double infections among these principal serovars were also detected in all our
      study groups but at a low overall frequency of 3%. Serovar D was the major agent
      involved in the aetiology of chlamydial infection in both children and adults
      though serovar F was the most frequent in newborn infants. Serovar H was
      relatively less frequent in symptomatic children. No trachoma-related serovars
      were detected, confirming the rarity of this disease in Papua New Guinea. In
      contrast, although clinical cases of lymphogranuloma venereum have not been
      described in the country, the detection of serovar L3 in this study suggests that
      it may occur. However, the association of L3 also with childhood infection
      indicates that it may be causing the same pathology as the serovars D-K that are
      associated with non-ulcerative sexually transmitted infections.

PMID- 19583098
TI  - The use of seatbelts in Port Moresby 12 years after the seatbelt legislation in
      Papua New Guinea.
AB  - The aim of this study was to assess the rate of seatbelt use by drivers and front
      seat passengers in Port Moresby, 12 years after the seatbelt legislation in 1993.
      Before the legislation, the rate of seatbelt usage was only 13.3% for drivers and
      11.4% for front-seat passengers. Use of seatbelts was assessed by observers at
      the main city roundabout. 50% of male drivers, 78% of female drivers, 49% of
      Papua New Guinean drivers and 69% of expatriate drivers wore seatbelts. Among the
      young drivers (teenagers aged < 20 years) 55% wore seatbelts. Of the front-seat
      passengers, 37% of males and 58% of females wore seatbelts. Female drivers and
      female front-seat passengers were more likely to wear seatbelts than males (OR
      2.55 [95% CI 1.53-4.23] and 2.34 [95% CI 1.32-4.14]). The front-seat passengers
      were more likely to be wearing seatbelts if the drivers wore theirs (OR 2.70 [95%
      CI 1.60-4.55]). Proportionately more drivers and front-seat passengers were
      wearing seatbelts than during the pre-legislation period, but more seatbelt
      education and awareness is needed because of the increasing number of road
      traffic accidents in Papua New Guinea.

PMID- 19583099
TI  - Large-vessel injuries of the neck admitted to Chongqing Emergency Medical Centre,
      China and Port Moresby General Hospital, Papua New Guinea, 1996-2006.
AB  - Stab wounds are the main cause of large-vessel injuries in the neck and they have
      a fairly good prognosis when the patient receives expeditious and appropriate
      management. The objective of this study is to present the experience of managing
      patients with large-vessel injuries in the neck. A retrospective study was
      carried out involving 22 cases with vessel injuries in the neck over the past 10
      years. Stab wounds accounted for 77% of this series (17 of 22 patients). All 22
      cases were treated operatively. The overall survival rate was 95%. One patient
      died on the operating table because of torrential haemorrhage into the chest.
      Complications included one thrombosis of the right subclavian artery, and five
      cases of haemothorax, all of which resolved. Successful salvage of patients with
      major vessel injuries in the neck depends on familiarity with the anatomy,
      accurate and timely clinical diagnosis and expedient surgical intervention.
      Patients with haemodynamic instability, rapidly expanding cervical haematomas or
      uncontrollable bleeding require immediate operative intervention, forgoing any
      diagnostic study. Stable patients may undergo radiological studies to detect
      occult injuries that may result in late morbidity such as false aneurysms and
      arteriovenous fistulae.

PMID- 19583100
TI  - Body size of Papua New Guineans: a comparison of the body mass index of adults in
      selected urban and rural areas of Papua New Guinea.
AB  - This is a cross-sectional study conducted in Port Moresby and 3 rural areas of
      Papua New Guinea from 1999 to 2002. These areas were selected because of their
      specific characteristics such as modernity, geographical location and remoteness.
      The aim of the study was to compare the body mass index (BMI) of selected urban
      and rural populations. When age was standardized, in urban and periurban
      populations, the mean BMI increased with age to about 40 years, plateaued and
      then decreased in older age. The BMI was higher in Port Moresby than in the other
      study areas: many people in Port Moresby were overweight (40%) and obese (21%),
      and by gender, 26% of females and 16% of males were obese. In Manus, the
      prevalence of overweight and obesity was 36% and 18% respectively. In both Port
      Moresby and Manus, more women than men were obese. Obesity was not a problem in
      rural areas of Strickland and Central Province. In rural Central Province 52% of
      subjects had a BMI < 20 kg/m2. Obesity is becoming a public health problem in the
      urban areas. The high prevalence of overweight and obesity corresponds with the
      high intake of refined carbohydrates and fatty foods in urban and periurban
      areas. It will be necessary to carry out health awareness and education on the
      risk factors associated with obesity in the urban and periurban areas and promote
      healthy environments: healthy foods should be available and affordable, and the
      accessibility and safety of exercise and walking tracks must be supported by the
      community and government agencies.

PMID- 19583102
TI  - He mana'o: June 2009.

PMID- 19583101
TI  - Scrub typhus (Orientia tsutsugamushi), spotted fever (Rickettsia australis) and
      dengue fever as possible causes of mysterious deaths in the Strickland Gorge area
      of Southern Highlands and West Sepik Provinces of Papua New Guinea.
AB  - A medical investigation was carried out in April 2001 into an outbreak of a
      mysterious haemorrhagic disease and deaths in the remote picturesque Strickland
      River area of Papua New Guinea (PNG). The area is in part of the Southern
      Highlands and West Sepik Provinces and situated downstream from the Porgera Joint
      Venture gold mine. 9 villages were visited and 140 persons, consisting of
      immediate blood relatives of the deceased (cases) and others in the village
      picked at random (controls), were physically examined. Specimens of blood, urine
      and faeces were collected from each person for laboratory tests in PNG and
      Australia. Positive sera for dengue (15%) and Japanese encephalitis (JE) (6%)
      were identified. Surprisingly, a number of the sera were positive for scrub
      typhus (Orientia tsutsugamushi) (28%) and spotted fever (Rickettsia australis)
      (11%). The last reported cases of scrub typhus in PNG were during World War Two
      among the allied troops. This is the first time spotted fever (R. australis) has
      been reported in PNG. These conditions may have been the cause of the deaths
      described by the villagers. However, there were significantly more dengue
      positive results among relatives of the deceased than non-relatives though no
      such difference was found with rickettsial infections: haemorrhagic dengue fever
      is thus the most likely cause of this recurring outbreak. Mining did not appear
      to be a direct causal factor for the deaths in the area.

PMID- 19583103
TI  - A practical approach to the healthcare crisis: the current challenges facing
      Hawai'i and the nation (part 1 of 2).
AB  - Although there is consensus regarding the existence of a healthcare crisis, that
      point is where the consensus stops, even within defined professional and
      demographic groups. Clearly there is evidence that we must address a growing
      societal expenditure for healthcare, an aging and more complex patient
      population, a shortage of physicians and other health care providers, and health
      outcomes disparities amongst population groups. This article emphasizes how these
      factors impact healthcare nationally and in Hawai'i. The second part of this
      series outlines approaches that can enhance health in the United States without
      creating economic collapse.

PMID- 19583104
TI  - Improving living renal transplant: lessons from a multi-ethnic transplant
      program.
AB  - Living-renal transplant (LRT) is the most effective treatment for endstage renal
      disease (ESRD), and innovative strategies to increase donation are needed. We
      reviewed our ethnically/culturally diverse program to identify factors that
      contribute to donors' decision to participate. Records of 110 LRT
      (related:unrelated = 66:44) and respective donors (1999-2005) were reviewed for
      demographics, outcome, education, employment, language, religion, and motivation.
      One and 5-year graft survival were 98.2% and 92% respectively. Mean donor age was
      41.1 yrs with Men:Women = 62:48 and similar ethnicity to recipients. Donors
      tended to be married (65.5%), educated (31.8% -- high school, 58.1% -- additional
      education/degree), employed (84.4%), religious (55.9%) and English-speaking
      (73.8%). Successful donors were motivated: 54% traveled from off-island, and
      10.9% had prior acts of altruism. Proper referral, identification & education of
      donors, and individual motivation of potential donors are key factors required
      for LRT. Continued efforts to overcome educational/language/cultural barriers are
      necessary to assist patients in finding donors and increasing LRT.

PMID- 19583105
TI  - First reported United States case of Legionella pneumophila serogroup 1 pneumonia
      in a patient receiving anti-tumor necrosis factor-alpha therapy.
AB  - Legionellosis has been reported to be an extremely rare disease in Hawai'i. The
      authors report a case of a 67-year-old woman with a history of rheumatoid
      arthritis treated with long-term adalimumab who developed severe right-sided
      community-acquired pneumonia and a parapneumonic effusion. Legionella pneumophila
      serogroup 1 was confirmed as the microbiologic cause based on a positive urine
      Legionella antigen as well as direct fluorescent antibody and Legionella culture
      of bronchoalveolar lavage. This is the first reported case of Legionella
      pneumonia associated with anti-tumor necrosis factor (TNF)-alpha therapy in the
      United States. There have been several reports of an increased association
      between legionellosis and treatment with a TNF-alpha antagonist. With the
      increasing use of TNF-alpha antagonists, Legionella pneumophila should be
      recognized as a potential re-emerging pathogen. Clinicians should particularly
      consider the diagnosis of legionellosis in patients who are immunocompromised,
      including those who receive anti-TNF-alpha therapy, or who have severe pneumonia.
      In such cases, there should be a low threshold for including empiric Legionella
      antimicrobial coverage until the diagnosis can be confirmed or reasonably
      excluded.

PMID- 19583106
TI  - Viral hepatitis in a homeless shelter in Hawai'i.
AB  - It is estimated that as many as 21,000 people in the state of Hawai'i may be
      infected with HCV Most of those infected with viral hepatitis are unaware they
      are infected. Complications from viral hepatitis include liver cirrhosis and
      hepatocellular carcinoma. Hawai'i has the highest incidence of hepatocellular
      carcinoma in the United States. In 2003 there were over 6000 homeless and over
      155,000 people at-risk of becoming homeless living in the state of Hawai'i. Risk
      factors for hepatitis, such as drug use, tattoos, sexual contact, and sharing of
      personal hygiene equipment are more prevalent in the homeless population. To
      determine the incidence of hepatitis B and C among a population of homeless
      individuals, a health fair was held at a Honolulu area homeless shelter with
      approximately 200 residents. The incidence of hepatitis B and C was determined by
      anti-HCV and HBsAg blood tests. A survey was also conducted regarding risk
      factors and basic demographics. Fifty-nine homeless adults volunteered for
      testing and took the survey. Thirty-one (52%) volunteers were born in Micronesia,
      twenty-four (41%) were born in the United States, two (3%) were born in Samoa,
      one (2%) was born in the Philippines, and one (2%) was born in the Marshall
      Islands. Forty adults were tested for Hepatitis C antibody, three of which tested
      positive. The primary risk factor among this group was jail time (100%), followed
      by illegal drug injection (67%), tattoos (67%), ear/body piercing (67%), snorting
      drugs (33%), blood transfusions (33%), and a sex partner with hepatitis (33%).
      Forty adults were also tested for HBsAg, One of which tested positive. This was a
      recent immigrant from Micronesia. Homeless people in Hawai'i are more likely to
      have hepatitis B or C because risk factors are common among this population.
      Additionally a large proportion of Hawai'i's homeless people come from the
      Pacific Islands, where the prevalence of hepatitis B is one of the highest in the
      world. In addition there are significant risks of hepatitis spread among the
      homeless and into the general population as many homeless do not realize they are
      infected. The health fair approach was an effective means for screening homeless
      people for hepatitis B and C. Our preliminary information suggests homeless
      shelters may be a good place for education, screening, and possibly interventions
      as well.

PMID- 19583107
TI  - An evaluation tool to measure cultural competency in graduate medical education.

PMID- 19583108
TI  - Assessing the needs for HIV medical care in Hawai'i.
AB  - To assess HIV medical care needs in Hawai'i, data was collected through surveys
      of both providers and consumers, from insurance companies, from the Department of
      Health, and from key programs who serve the HIV-infected population. HIV care in
      Hawai'i is provided through a mix of private, public and charitable sources, with
      most ancillary services provided separately by AIDS Service Organizations.
      Private providers with a specialty in HIV care are not being replaced at the rate
      which they retire or depart. Heavy reliance on public assistance to pay for care
      and patient characteristics such as substance abuse, limit choice of providers
      for some patients. Institutions are playing a greater role in filling patient
      care needs. It was found that most patients in care are highly satisfied with
      their care providers. People living with HIV who are not in care are likely to
      have multiple challenges which affect access to care such as homelessness,
      poverty, low levels of education, being of Asian Pacific Islander ethnicity, and
      receiving public assistance. Those who adhere to their medication are most likely
      to be employed and to have received counseling by a pharmacist, while those who
      are from Hawai'i and who were infected through injection drug use are less likely
      to be adherent. Supporting more than one provider option and linking with
      ancillary services may help keep HIV patients in care.

PMID- 19583109
TI  - The Hawai'i Community Resource Obesity Project: results from the Lifestyle
      Enhancement Program.
AB  - OBJECTIVE: The purpose of this study was to describe the effects of a community
      based, multidisciplinary team-led, lifestyle modification program on short-term
      weight loss in a morbidly obese (mean BMI 40.8 kg/m2), predominantly Native
      Hawaiian population. METHODS: Descriptive study comparing weight loss over time
      in intervention and control groups. Of 217 eligible participants in the
      intervention group, 58% were Native Hawaiian. RESULTS: Participants in the
      intervention group experienced a modest yet significant weight loss, while the
      control group gained weight. The mean 12-month weight loss in the intervention
      group was 4.1 pounds (1.9 kg). High program attrition rates hindered program
      effectiveness and data collection. CONCLUSION: Although the weight loss in the
      study group was moderate, it was significant over the control group whose members
      actually had an increase in average weight over the study period. Further
      research into pre-treatment correlates of attrition in this population is needed
      in order to eliminate health disparities among Native Hawaiians.

PMID- 19583110
TI  - A case report and literature review of group C streptococcal pneumonia.
AB  - Group C streptococci rarely cause severe disease in humans. The authors report a
      15-year-old girl with group C streptococcal pneumonia. No immune deficiencies
      were detected in our patient and investigation of virulence factors including
      emmL, sag A, spegg and smeZ genes failed to reveal insight into why the isolated
      group C streptococcal strain was so virulent. Fourteen other reports of primary
      group C streptococcal pneumonia were reviewed.

PMID- 19583111
TI  - Professionalism in the teacher-learner relationship in medical schools:
      mistreatment.

PMID- 19583112
TI  - Adolescent and young adult cancer care: a national and local problem.

PMID- 19583113
TI  - Schizophrenia.

PMID- 19583114
TI  - Leaving your job? What about your retirement account?

PMID- 19583115
TI  - Preventing back injuries.

PMID- 19583116
TI  - Prevention of mother-to-child HIV transmission and management of paediatric HIV
      infection in Jamaica.

PMID- 19583117
TI  - The HIV epidemic in the Caribbean: meeting the challenges of achieving universal
      access to prevention, treatment and care.
AB  - The HIV prevalence in the Caribbean is estimated at 1.0% (0.9% - 2%) with 230,000
      persons living with HIV/AIDS. HIV rates vary among countries with the Bahamas,
      Guyana, Haiti and Trinidad and Tobago having HIV rates of 2% or above while
      Cuba's rate is less than 0.2%. However throughout the Caribbean, HIV rates are
      significantly higher among those groups most at risk such as commercial sex
      workers, men who have sex with men and crack/cocaine users. The Caribbean
      Community (CARICOM) Heads of Governments declared AIDS to be a regional priority
      in 2001. The Pan Caribbean AIDS Partnership (PANCAP) was formed to lead the
      regional response to the HIV epidemic. National HIV Programmes have made definite
      progress in providing ARV treatment to persons with HIV/AIDS and reducing death
      rates due to AIDS, decreasing HIV mother-to-child transmission and providing a
      range ofHIVprevention programmes. However HIV stigma remains strong in the
      Caribbean and sexual and cultural practices put many youth, women and men at risk
      of HIV The Caribbean has set itself the goal of achieving universal access to HIV
      prevention, treatment and care. Several challenges need to be addressed. These
      include reducing HIV stigma, strengthening national responses, scaling-up better
      quality prevention programmes with greater involvement of vulnerable populations,
      more supportive HIV policies and wider access to ARV treatment with better
      adherence. In addition, there needs to be improved coordination among PANCAP
      partners at the regional level and within countries.

PMID- 19583118
TI  - Paediatric and perinatal HIV/AIDS in Jamaica an international leadership
      initiative, 2002-2007.
AB  - BACKGROUND: Paediatric and Perinatal HIV/AIDS remain significant health
      challenges in the Caribbean where the HIV seroprevalence is second only to Sub
      Saharan Africa. METHOD: We describe a collaborative approach to the prevention,
      treatment and care ofHIVin pregnant women, infants and children in Jamaica. A
      team of academic and government healthcare personnel collaborated to address the
      paediatric and perinatal HIV epidemic in Greater Kingston as a model for Jamaica
      (population 2.6 million, HIV seroprevalence 1.5%). A five-point plan was utilized
      and included leadership and training, preventing mother-to-child transmission
      (pMTCT), treatment and care of women, infants and children, outcomes-based
      research and local, regional and international outreach. RESULTS: A core group of
      paediatric/perinatal HIV professionals were trained, including paediatricians,
      obstetricians, public health practitioners, nurses, microbiologists, data
      managers, information technology personnel and students to serve Greater Kingston
      (birth cohort 20,000). During September 2002 to August 2007, over 69 793 pregnant
      women presented for antenatal care. During these five years, significant
      improvements occurred in uptake of voluntary counselling (40% to 91%) and HIV
      testing (53% to 102%). Eight hundred and eighty-three women tested HIV-positive
      with seroprevalence rates of 1-2% each year The use of modified short course
      zidovudine or nevirapine in the first three years significantly reduced mother-to
      child transmission (MTCT) of HIV from 29% to 6% (RR 0.27; 95%0 CI--0.10, 0.68).
      During 2005 to 2007 using maternal highly active antiretroviral therapy (HAART)
      with zidovudine and lamivudine with either nevirapine, nelfinavir or
      lopinavir/ritonavir and infant zidovudine and nevirapine, MTCT was further
      reduced to an estimated 1.6% in Greater Kingston and 4.75% islandwide. In five
      years, we evaluated 1570 children in four-weekly paediatric infectious diseases
      clinics in Kingston, St Andrew and St Catherine and in six rural outreach sites
      throughout Jamaica; 24% (377) had HIV/AIDS and 76% (1193) were HIV-exposed. Among
      the infected children, 79% (299 of 377) initiated HAART resulting in reduced HIV
      attributable childhood morbidity and mortality islandwide. An outcomes-based
      research programme was successfully implemented. CONCLUSION: Working
      collaboratively, our mission of pMTCT of HIV and improving the quality of life
      for families living and affected by HIV/AIDS in Jamaica is being achieved.

PMID- 19583119
TI  - Evolving care of HIV-infected pregnant women in Jamaica--from nevirapine to
      HAART.
AB  - BACKGROUND: The Ministry of Health, Jamaica, is scaling-up programmes to improve
      the health of HIV-positive pregnant women according to the modified WHO
      recommended preventative mother to child transmission (pMTCT) regimens of therapy
      based upon the mother's clinical and immunological status. Highly-active
      antiretroviral drugs (HAART) can result in successful pMTCT to < 1%. We report
      the clinical and immunological characteristics of HIV/AIDS in an era of evolving
      treatment and care of HIV-infected pregnant Jamaican women. SUBJECTS AND METHOD:
      Clinical records were reviewed of patients registered in antenatal clinics in
      Greater Kingston and St. Catherine, Jamaica (annual birth cohort--20,000) between
      September 2002 and August 2006. Disease status was determined using the Centers
      for Disease Control and Prevention (CDC) classification system for adult
      HIV/AIDS. Demographic, clinical and laboratory data were documented and analyzed.
      RESULTS: During the four-year period, 571 HIV-infected women were enrolled; 62%
      from Victoria Jubilee Hospital, 25% from Spanish Town Hospital and 13% from the
      University Hospital of the West Indies. Mean age was 27-29 (range 15-41) years,
      median parity was 2 (range 0-9) and 68-70% were unemployed. Ninety-five per cent
      had live births. CDC categories of illnesses were A--mild disease in 82% (n=473),
      B--moderate disease in 4.4% (n=24) and C--severe disease in 1.4% (n=8) while 12%
      (n=66) had insufficient data. During the first three years, CD4+ cell counts were
      evaluated in only 2.5% (10 of 406) of patients with median of 344 cells/microL,
      compared to CD4 evaluation in 50% (83 of 165 women) in the last year with median
      of573 cells/uL. Antiretroviral (ARV) medications primarily for pMTCT were given
      to 89% (n=506) ofwomen. Of these, uptake of HAART increased during years 1-3 from
      2-3% to 62% in year four Within two years post-partum, 24 women died, 92%
      (n=22)from the direct complications of HIV/AIDS. CONCLUSION: A comprehensive
      system of care of HIV in the peripartum period has been developed in Jamaica.
      Detailed medical evaluation during pregnancy is performed with modern guidelines
      and increasing laboratory availability of CD4+ cell counts and viral loads. We
      believe declining HIV infection rates in Jamaican infants and healthier mothers
      are a direct consequence of increased testing in pregnancy with early diagnosis
      and initiation of HAART-based pMTCT regimens in pregnant women.

PMID- 19583120
TI  - Effectiveness of antiretroviral therapy in treating paediatric HIV/AIDS in
      Jamaica.
AB  - BACKGROUND AND PURPOSE: Paediatric HIV/AIDS remains a significant challenge in
      developing countries. We describe the effectiveness of interventions in HIV
      infected children attending Paediatric Infectious Diseases Clinics in Jamaica.
      METHODS: One hundred and ninety-seven HIV-infected children were followed
      prospectively in multicentre ambulatory clinics between September 1, 2002 and
      August 31, 2005, in the Kingston Paediatric and Perinatal HIV/AIDS Programme,
      Jamaica, and their outcomes described. RESULTS: Median follow-up was 23 child
      months (interquartile range [IQR] 12-31) with 12 children (6.0%) lost to follow
      up and deaths (n=13) occurred at 4.64 per 100 child-years of follow-up. Median
      age was 5.0 years (IQR 2.2-8.1) and 32.1% had Centers for Disease Control and
      Prevention (CDC) category C disease at enrollment; 62% were ever on
      antiretroviral therapy (ART) with median duration of 15.4 months (IQR 5.5-25.5);
      85% initiated ART with zidovudine/lamivudine/nevirapine. Mean weight-for-height
      0.13 +/- 1.02 (mean difference -1.71 [95% Confidence interval (CI) -2.73, -0.69];
      p = 0.001) and body mass index-for-age 0.05 +/- 1.11 (mean difference -1.11, [CI 
      1.79, -0.43]; p = 0.002); z scores increased after 24 months on ART; however,
      children remained stunted. Reductions in the incidence of hospitalizations (mean
      diff 30.95, [CI 3.12, 58.78]; p = 0.03) and in episodes of pneumonia, culture
      positive sepsis and tuberculosis occurred in those on ART. CONCLUSIONS: A
      successfully implemented ambulatory model for paediatric HIV care in Jamaica has
      improved the quality of life and survival of HIV-infected children.

PMID- 19583122
TI  - Safety of antiretroviral drug therapy in Jamaican children with HIV/AIDS.
AB  - BACKGROUND: HIV has been a leading cause of death in Jamaican children aged < or
      = five years. Antiretroviral drugs (ARVs) are increasingly available in Jamaica
      through the Global Fund. Adverse effects of ARVs are a major cause for non
      adherence to medications. Knowledge of the use and side effects of these drugs
      are crucial in the management of HIV-infected children as we scale-up the use of
      antiretroviral therapy, islandwide. We evaluated the adverse events and safety of
      antiretroviral therapy in children attending four Infectious Disease Clinics in
      Kingston, Jamaica, a resource limited setting. METHODS: Data for children
      prospectively enrolled in the Kingston Paediatric and Perinatal HIV/AIDS
      Programme during September 2002 to April 2005 were analyzed. RESULTS: Among 121
      HIV-infected children, 77 (64%) were on ARVs, 90% had CDC class C disease, 60%
      were males and perinatal transmission predominated. AZT/3TC based regimen was
      utilized in 93%, trimethoprim/sulphamethoxazole prophylaxis was used in 100% and
      five were completing antituberculous drugs. Anaemia occurred in all patients,
      with increased severity in those on ARVs. Macrocytosis occurred in 83% and
      thrombocytopenia in 8% of those on ARVs. Elevation of bilirubin, aspartate
      transaminase (AST) and alanine transaminase (ALT) levels and reversed albumin to
      globulin ratio prior to commencing AR Vs, with significantly lower prevalence
      following use of ARVs emphasized the severity of HIV disease at time of ARV
      initiation. Clinical adverse reactions were uncommon and included nail
      discoloration (8%), vomiting (7%), nausea (3%), peripheral lipodystrophy (4%) and
      abnormal dreams (1%). Ten children required change of ARV medication because of
      severe adverse effects: three for severe anaemia with repeat blood transfusions,
      three for severe nevirapine-associated rash and four for indinavir-associated
      haematuria. CONCLUSIONS: ARVs are being successfully initiated in HIV-infected
      Jamaican children using the public health model. The excellent safety profile,
      good tolerance and few reported significant adverse effects augur well as
      antiretroviral therapy is scaled-up islandwide.

PMID- 19583121
TI  - Adherence to antiretroviral drug therapy in children with HIV/AIDS in Jamaica.
AB  - OBJECTIVE: We aimed to describe the adherence patterns to antiretroviral therapy
      (ART) in a cohort of HIV-infected children. METHODS: Between the periods May to
      October 2005, 63 HIV-infected children and their caregivers recruited
      consecutively at four Paediatric Infectious Disease Clinics in Greater Kingston
      and St. Catherine, Jamaica, were interviewed. Adherence was defined as no missed
      doses in the last four days. Biomedical markers and factors associated with
      adherence were explored. RESULTS: Global adherence level was 85.7% (54/63) and
      was significantly higher for children in residential care (approaching 100%)
      compared to 76.3% for children in family care (p = 0.008). Children had median
      age 7.9 years (range 0.8 - 19.4 years) and 57% were male. Median duration on ART
      was 18.3 months (range 0.1 - 123.8 months). Median CD4 count and per cent
      available for 95.2% (60/63) and 92.1% (58/63) children were 440 cells per microL
      (IQR 268-897 cells/pL) and 24.9% (IQR 15.6 - 42.7%), respectively. Median viral
      load was 9.60 x 103 copies/ml (IQR 0.05 x 10(3) - 52.50 x 10(3)) with 16% (10/63)
      having viral loads < or = 50 copies/ml. Children in residential care (n=26),
      receiving directly observed therapy had higher CD4 counts (p = 0.006) and CD4 per
      cent (p < or = 0.001). Factors associated with non-adherence were primarily
      caregiver related, especially long work hours (p = 0.002) and nausea as a side
      effect of ART (p = 0.007). Non-adherence was positively correlated with missing
      clinic appointments (r = 0.342, p = 0.009) and increasing age of child (r =
      0.310, p = 0.013). CONCLUSION: In resource-limited settings, psychosocial factors
      contribute significantly to nonadherence and should complement biomedical markers
      in predicting adherence to antiretroviral therapy in children.

PMID- 19583123
TI  - Renal manifestations in HIV-infected Jamaican children.
AB  - BACKGROUND: Documentation regarding the renal complications of paediatric HIV
      infection from developing countries is scarce. In the era prior to highly active
      antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed
      HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD)
      and death within a few months of diagnosis. With increased public access to
      antiretroviral therapy since 2002 and subsequent survival, renal complications
      are increasingly recognized among the surviving cohort of infected children.
      METHODS: A cohort of 196 HIV-infected children was followed in four multicentre
      ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the
      Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the
      clinical presentations and natural history of those patients who developed renal
      complications. RESULTS: Urinary tract infections were the most common diagnosis,
      occurring in 16.8% of patients, with a high recurrence rate and the most common
      organism was Escherichia coli. Four of seven patients who started indinavir
      developed complications of nephrolithiasis and tubulointerstitial nephropathy.
      Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male.
      Median age at diagnosis was five years; all presented with advanced HIV disease,
      nephrotic syndrome or nephrotic range proteinuria and three with chronic renal
      failure. Patients received standard medical management and were initiated on
      angiotensin-converting enzyme (ACE) inhibitors and HAART While the mortality
      ratio was 50%, only one death was associated with HIVAN and the median survival
      time was 3.1 years. CONCLUSIONS: HIV-infected children present with a variety of
      renal complications. With improved survival since the introduction of HAART, the
      incidence of HIVAN is expected to increase among this maturing paediatric cohort.
      Early detection and treatment will optimize the outcomes for these children.

PMID- 19583124
TI  - Absence of opportunistic parasitic infestations in children living with HIV/AIDS
      in children's homes in Jamaica: pilot investigations.
AB  - BACKGROUND: Many children living with HIV/AIDS in developing countries are
      infected with intestinal parasites. These infections add unnecessary morbidity to
      children already suffering the clinical insult of living with HIV/AIDS.
      OBJECTIVE: To determine the prevalence and potential risk factors for intestinal
      parasitic infections in HIV-infected children living in two institutions in
      Jamaica. METHODS: A total of 82 faecal specimens were collected from 41 HIV
      infected children (age range 2-14 years) who resided in two Children's Homes. A
      structured 42-item questionnaire was administered to caregivers to obtain
      clinical and demographic data on each child. Faecal specimens from each patient
      were examined using standard microbiological techniques and Cryptosporidium
      antigen detection was conducted using a commercially available enzyme immunoassay
      (EIA). RESULTS: No opportunistic intestinal parasites were identified in this
      study. Non-opportunistic parasites diagnosed included Giardia lamblia (12.2%) and
      Ascaris lumbricoides (2.4%) while the commensals Endolimax nana and Entamoeba
      hartmanni were found in 4.9% and 2.4% of children, respectively. CONCLUSION:
      Children living with HIV/AIDS in institutions in Jamaica that are closely
      supervised do not appear to be at substantial risk for intestinal parasites. This
      may be due to the strict clinical monitoring of the children and personal and
      environmental hygiene practices.

PMID- 19583125
TI  - Clinical manifestations of adolescents with HIV/AIDS in Jamaica.
AB  - OBJECTIVE: To characterize the clinicopathological manifestations and outcomes of
      a cohort of HIV-infected Jamaican adolescents. METHODS: This is a retrospective
      cohort study to determine demographic, clinical, immunological characteristics,
      antiretroviral uptake and mortality in 94 adolescents aged 10-19 years followed
      in the Kingston Paediatric and Perinatal HIV/AIDS Programme (KPAIDS) between
      September 2002 and May 2007. Parametric and non-parametric tests are used to
      compare variables. RESULTS: The median age at initial presentation was 10.0 years
      (interquartile range (IQR) 7.0-12.0 years), 54.3% (51) were female (p = 0.024),
      transmission was primarily mother-to-child (70, 73.4%), with 87% (61) of the
      latter presenting as slow progressors. Sexual transmission accounted for 19.1%
      and there was significant female predominance (n=15; p = 0.024). At most recent
      visit, perinatally infected adolescents were more likely (p < 0.0001) to reside
      with a non-parent (n=42) than a biological parent (n=19) and most had Centers for
      Disease Control and Prevention (CDC) category C (35/50%) disease, whereas the
      majority of non-perinatally infected children were classified CDC category A.
      Mean z scores for height-for-age was -1.47 +/- 1.21 (n=77), weight-for-age -1.06
      +/- 1.44 (n=80) and BMI-for-age -0.34 +/- 1.21 (n=76) respectively; females
      (n=41) were taller than males (n=36) at their current height (p = 0.031).
      Lymphadenopathy (82%), dermatitis (72.0%), hepatomegaly (48%) and parotitis (48%)
      were the most common clinical manifestations, with significant predilection for
      lymphadenopathy (p < or = 0.0001), dermatitis (p = 0.010), splenomegaly (p =
      0.008), hepatomegaly (p = 0.001) and parotitis (p = 0.007) among perinatally
      infected children. Median baseline CD4+ cell count was 256.0/microL (IQR 71.0 -
      478.0 cells/microL); median most recent CD4+ cell count was 521/microL (IQR 271.0
      - 911.0 cells/microL). Seventy-six per cent (n=71) were initiated with highly
      active antiretroviral therapy (HAART) and 62 (87.3%) were currently receiving
      first-line therapy. Six behaviourally infected females became pregnant, resulting
      in five live births. There were seven deaths (7.4%). CONCLUSION: This study
      comprehensively characterizes HIV infection among perinatally infected teens with
      predominantly slow-progressor disease and an increasing population of sexually
      infected adolescents. As the cohort transitions to adulthood, adolescent
      developmental, mental health and life planning issues must be urgently addressed.

PMID- 19583126
TI  - HIV-related mortality in Jamaican children.
AB  - OBJECTIVE: Paediatric HIV is a leading cause of morbidity and mortality
      worldwide. We describe HIV-related mortality in a cohort of HIV-infected Jamaican
      children and identified factors which influenced survival. METHODS: A
      retrospective descriptive study was conducted for the period March 2003 -
      December 2005 at Cornwall Regional Hospital, Montego Bay, Jamaica. We summarized
      demographic and clinical data of deceased and living perinatally HIV-infected
      children and identified factors that influenced survival of rapid and slow
      progressors. Rapid progressors are HIV-infected children identified clinically
      before age 2 years and slow progressors after age 2 years. RESULTS: There were 9
      (180%) HIV/AIDS-related deaths among 50 HIV-infected children of whom 23 (46%)
      were males and 21 (43%) were AIDS orphans. Five children (10%0) received ARV
      prophylaxis, 31 (62%) were breastfed and 39 (78%) received HAART Surviving
      children displayed primarily non-AIDS defining illnesses (pneumonia and sepsis)
      but there was no difference in AIDS-defining illnesses among living and deceased
      children. The median age at diagnosis was 26 months (range 3-121; IQR 10, 54).
      The median age at death was 30 months (range 7-122 months; IQR 17, 118). Both
      surviving and deceased children presented with primarily moderate symptoms at
      diagnosis (21, 42%) and death (7, 78%). In rapid progressors, 19 of 20 (95%) on
      HAART remained alive and all 4 (100%) who did not receive HAART died. The
      mortality rate in children on HAART was 30.78 per 100 person years and 48 per 100
      person years in children not receiving HAART. CONCLUSIONS: HAART is the only
      factor identified which prolonged survival for HIV-infected children who are
      rapid progressors, have AIDS-defining illnesses and are orphans.

PMID- 19583127
TI  - Challenges and successes of HIV voluntary counselling and testing programme in
      antenatal clinics in greater Kingston, Jamaica.
AB  - ISSUES: Voluntary counselling and testing (VCT) is a critical issue impacting HIV
      disease management from a national and global perspective. In Jamaica (population
      2.6 million), 2% of women in antenatal clinics are HIV-positive and mother-to
      child-transmission (MTCT) accounted for 7% of all reported cases in 2002.
      Notwithstanding this, VCT was ad hoc and not standardized. In 2003, a structured
      VCT programme was developed islandwide with over 300 VCT service providers and 16
      qualified trainers. DESCRIPTION: We describe the challenges and successes of VCT
      provided by five trained research nurses in the Perinatal HIV/AIDS Programme in
      Kingston which services 19,000 pregnant women per year in three major maternity
      centres and their 42 feeder antenatal clinics. LESSONS LEARNED: The VCT model
      used was group education, opt-out individual testing, individual post-test
      counselling for seropositives and informing seronegatives of their negative
      status. Major challenges encountered included lack of quality control of the
      counselling process and lost opportunities for un-booked women who presented in
      labour However successes enjoyed included client assessment of risk behaviours
      with appropriate lifestyle changes, increased uptake of HIV testing and adherence
      to care for themselves and their infants, as well as reduction in stigma.
      RECOMMENDATIONS: VCT has proven to be an important intervention that enabled
      improvement in the awareness, prevention and control of HIV in Jamaican pregnant
      women. Nurses who are appropriately trained in VCT can play a pivotal role in
      successful provision of VCT services.

PMID- 19583128
TI  - Voices of the women: feedback from women of child-bearing age who are living with
      HIV can help improve efficacy of psychosocial interventions.
AB  - BACKGROUND: We hypothesized that voluntary counselling and testing during
      pregnancy are necessary but not sufficient to provide the holistic psychosocial
      support needed by Jamaican women living with HIV and/or AIDS. Based on this
      hypothesis, we investigated a range of coping methods and support systems used by
      HIV-infected women and a group of their HIV-negative counterparts before, during
      and immediately after their pregnancies. METHODS: Women attending obstetric
      clinics in urban Jamaica completed a quantitative survey aimed at discovering
      coping behaviours, social and spiritual support systems. Pre-survey focus group
      studies and key informant interviews contributed to the design of the
      questionnaire while post-survey focus groups were used to probe the validity of
      the data gleaned from the questionnaire survey Survey data were analyzed using
      non-parametric tests for trend with independent univariate tests. RESULTS: Fifty
      five HIV-infected women and 51 HIV-negative women completed the survey Compared
      with HIV-negative women, more HIV-infected women reported both feeling depressed
      (p = 0.07) and having difficulty concentrating (p = 0.05) during the month
      immediately prior to the study. Other statistically significant differences
      included: HIV-infected women were more likely to pray, to sleep and to change
      eating habits in response to worry and stress (p = 0.001 in each instance).
      Although several women declared religious faith, significantly fewer HIV-infected
      women were willing to talk to a religious leader about their problems compared to
      their HIV-negative counterparts (p < 0.001). CONCLUSIONS: Participation of HIV
      infected women in post-survey focus groups augmented the survey findings. Many of
      the women reported negative emotions and some indicated serious challenges in
      accessing social support. The results point to the need for systematic
      documentation of psychosocial profiles as part of the approach to caring for
      these women. In addition, in the Jamaican sociocultural context, we recommend
      improved training of religious leaders and healthcare providers in psychosocial
      issues.

PMID- 19583129
TI  - Contact investigation in the prevention of mother-to-child transmission of HIV
      comparing urban and rural outcomes in Jamaica.
AB  - BACKGROUND AND PURPOSE: The contact investigators played a significant role in
      the decline of infectious syphilis in Jamaica and are likely important players in
      the prevention of mother-to-child transmission (PMTCT) in the HIV programme. A
      brief evaluation was done comparing the outcomes of contact investigation in
      Kingston and St. Andrew (KSA) with that of the contact investigation in two rural
      parishes. METHODS: The interview and field records for the seropositive antenatal
      clinic attendees for the period October 2004 to September 2005, in urban KSA,
      were compared with those for rural Clarendon and Portland. RESULTS: HIV
      seropositive pregnant women (n=88) were notified and/or referred to the parish
      contact investigators: 36 in KSA, 9 in Portland and 43 in Clarendon. The time
      from test date to interview date was almost twice as long for KSA (mean 27 days)
      than Portland (mean 15.7 days) and thrice that of Clarendon (mean 9 days). Mean
      disposition (case closure) times were for KSA: 19 days; Portland: 28 days and
      Clarendon: 15 days. Only 40% of the contacts were located for KSA and 48% of
      these tested positive for HIV For Portland, 73% were located and 8% tested
      positive. For Clarendon, 45% were located and 35% of these tested positive.
      CONCLUSIONS: On site same day HIV rapid testing is not always available so the
      contact investigator is an essential member of the pMTCT team in Jamaica. One of
      the programme outcomes (time to interview) was longer in the urban than the rural
      parishes while others (time to resolution of the case and percentage of contacts
      located and tested) had no consistent urban-rural differences.

PMID- 19583130
TI  - Predictors of HIV/AIDS confirmation and differences by guardian status in HIV+
      adolescents in Jamaica.
AB  - BACKGROUND: Approximately 25% of the cumulative AIDS cases in Jamaica involve
      adolescents and young adults. However the lives of adolescents living with HIV
      within Jamaica and the Caribbean have been understudied. OBJECTIVES: (1) To
      describe the sociodemographic characteristics of HIV+ Jamaican adolescents who
      have ever been a part of the Kingston Paediatric/Perinatal HIV Programme (KPAIDS)
      from September 1, 2002 to August 31, 2006 (2). To identify predictors of HIV/AIDS
      confirmation as well as factors associated or uniquely present in these
      adolescents by their guardian status. METHODS: Seventy-two HIV+ adolescents, ages
      10-19 years, were included. Factors studied included demographics as well as time
      to and time between HIV and AIDS confirmation. Data were analyzed by bivariate
      and multivariate statistics. RESULTS: The mean age of the adolescents was 12.6 +/
      2.8 years with slightly more males (52.8%) in the programme. There were equal
      proportions of adolescents living with HIV as with AIDS (43.1%). There were equal
      proportions who were lost to follow-up or deceased (8.3%). Twenty-two of them
      lived with parents, 25 with guardians and 18 in residential institutions. The
      primary mode of transmission was perinatal infection (68.1%), followed by sexual
      (20.8%), blood transfusion (2.9%) and unknown (8.3%). The mean time from HIV
      exposure to HIV confirmation and AIDS confirmation in mother-to-child
      transmission (MTCT) cases were 8.0 +/- 2.9 years and 9.6 +/- 3.3 years,
      respectively. In the multivariate analysis model, age and gender were significant
      in predicting time from HIV exposure to HIV confirmation. CONCLUSION: The
      majority of HIV-positive adolescents reside with parents and guardians and this
      might indicate support in spite of stigma and discrimination. However; the mean
      time to HIV confirmation in MTCT cases is quite long and must be reduced.

PMID- 19583131
TI  - Evaluation of adherence to highly active antiretroviral therapy in adults in
      Jamaica.
AB  - BACKGROUND AND PURPOSE: Highly active antiretroviral therapy (HAART) has improved
      morbidity and mortality and quality of life, revitalized communities and
      transformed the perception of HIV/AIDS from being a "death sentence" to a chronic
      illness. Strict and sustained adherence to medication is essential long-term
      viral suppression. In April 2005, an Adherence Support Programme was introduced
      to Jamaica's HIV Programme, whereby Persons Living with HIV/AIDS (PLWHA) who had
      achieved high levels of adherence were trained to provide support to other PLWHA
      in order to increase their adherence to HAART regimens. METHODS: A cross
      sectional survey of 116 individuals with advanced HIV and on HAART was performed
      in June and July 2006. RESULTS: Many participants were unemployed, poor persons
      with limited education. Based on self-report of seven-day adherence, 54.8% of
      persons were 95-100% adherent, 37.5% were 80-94% adherent and 7.7% were < 80%
      adherent. Having interacted with an adherence counsellor was not associated with
      adherence levels. Factors associated with nonadherence were: being away from home
      (38%), sleeping through dose-time (37%), forgetfulness (37%) and running out of
      pills (31%). Having no food (26.9%), not wanting to be seen taking medication
      (200%) and intolerable side effects (18.8%) were also reasons given. Only 44% of
      persons used aids to remind them of dose times. CONCLUSION: Adherence in this
      study group is low and may have worsened since 2005. More emphasis must be placed
      on preparing adults to start HAART The use of pillboxes and other reminders such
      as alarm clocks and cell phones must be reinforced.

PMID- 19583132
TI  - Isoniazid-resistant disseminated Mycobacterium tuberculosis in a Jamaican infant
      with HIV/AIDS.
AB  - A case report of isoniazid-resistant disseminated tuberculosis in a young child
      perinatally co-infected with human immunodeficiency virus (HIV-1) and the
      challenges managing this child in a resource-constrained setting.

PMID- 19583133
TI  - Bacille Calmette-Guerin lymphadenitis and immune reconstitution syndrome in HIV
      infected children on antiretroviral therapy in Jamaica.
AB  - The immune reconstitution inflammatory syndrome (IRIS) is a recognized
      complication associated with opportunistic infections occurring in HIV-infected
      individuals after the initiation of highly active antiretroviral therapy (HAART).
      We report on three HIV-infected infants with rapid progressor HIV disease who
      present with IRIS due to the BCG vaccine and occurring 3-6 weeks after initiation
      of HAART

PMID- 19583134
TI  - HIV infection, sexual abuse and social support in Jamaican adolescents referred
      to a psychiatric service.
AB  - BACKGROUND: Children and adolescents with HIV/AIDS often have
      psychological/psychiatric issues that require specialist intervention. We
      explored whether HIV infection acquired through sexual abuse led to particularly
      negative psychiatric outcomes and whether good social support is a protective
      factor in the development of undesirable psychiatric sequelae. METHODS: This
      study consists of a case series of five persons referred from the Paediatric
      Infectious Diseases Clinic to the Child Psychiatry Clinic, both at the University
      Hospital of the West Indies (UHWI) in Jamaica, during July 1 to November 30,
      2005. The patients were clinically assessed and diagnosed by a psychiatrist using
      the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM
      IV) criteria. Cases were compared according to gender, age, likely route of HIV
      infection, level offamily/social support and nature of psychiatric outcome.
      RESULTS: Adolescents who acquired HIV infection through sexual abuse reported
      more intense feelings of sadness and suicidal ideations. Those with good social
      support reported less intense feelings of sadness with no suicidal ideations and
      were more optimistic about their future regardless of the route of acquisition.
      Two of three adolescents who acquired HIV infection through sexual abuse and one
      of two who was perinatally infected required ongoing supportive psychotherapy to
      augment their social support, the characteristic most associated with favourable
      outcome. CONCLUSION: Both sexual abuse and HIV/AIDS are likely to have negative
      psychological consequences in children and adolescents. This psychological impact
      may be intensified when HIV infection results from sexual assault as opposed to
      other methods of transmission. The findings support the practice of providing HIV
      prophylaxis to all sexual assault victims of known or suspected HIV-positive
      perpetrators and of encouraging utilization of existing social support networks.

PMID- 19583135
TI  - Tattooing and perinatal HIV/AIDS in Jamaica.

PMID- 19583136
TI  - Speak up! Speak out! Building HIV and AIDS awareness among Jamaican school
      children.
AB  - BACKGROUND AND PURPOSE: The Government of Jamaica, through the Ministry of Health
      and other ministries, assisted by international funding agencies and members of
      non-governmental organizations, has diligently led the charge to reduce the
      incidence ofHIV and AIDS in Jamaica. Yet, the continued escalation in the
      infection rate attested to the need for education towards the reduction of stigma
      and discrimination, factors that fuel the spread of the virus. Significant
      efforts were made to woo corporations in Jamaica to redouble their efforts and
      provide resources to address the continued escalation of the AIDS epidemic in
      Jamaica. Scotiabank Jamaica responded with a unique educational initiative.
      METHODS: The Scotiabank National Primary Schools HIV and AIDS Debating
      Competition in 2006-2007 was conducted over a seven-month period. It was opened
      to primary-level, government and private institutions islandwide. RESULTS: A
      total of91 institutions competed with each other debating 16 moots (i.e., topics)
      in 417 debates from the first preliminary rounds through to the final. Moots
      reflected curricular and extracurricular concerns, emphasized the values of
      compassion, healthy lifestyles, critical thinking and child rights; they also
      sent messages of anti-discrimination, and parental and community
      responsibilities. Whereas communication between the organizers and the schools
      was sometimes challenging, schools subscribed to the activity (debates) for the
      awareness it brought and for the potential for developing students. Attempts were
      also made to raise awareness among teachers, parents and the general community.
      CONCLUSION: Feedback at the end acclaimed the debates as a valuable strategy for
      building awareness as well as development of student potential and unity around a
      common cause.

PMID- 19583137
TI  - [The challenges of influenza viruses].

PMID- 19583138
TI  - [Implications of anesthetic techniques on patients' recovery in laparoscopic
      cholecystectomy].
AB  - BACKGROUND/AIM: Different techniques of general anesthesia are used for
      laparoscopic cholecystectomy (LC). The aim of the study was to establish the best
      anesthetic technique for achieving better results during awakening affecting not
      only patient's recovery, but activities of anesthesiological team, as well.
      METHODS: The study was conducted as a prospective comparative clinical trial. The
      patients (n=90) were classified according to the applied anesthetic technique
      into two groups: Volatile Induction and Maintenance Anaesthesia (VIMA) with
      sevofluran and Target Controlled Infusion (TCI). The results relating to
      parameters of recovery after anesthesia and surgery were compared between these
      two groups. The following parameters were analysed: demographic patients'
      characteristics, duration of anesthesia, the times to eye opening, to respond to
      a command, to extubation, and to orientation, from the last anesthetic dose
      receiving until post anesthesia discharge (PAD), frequency of postoperative
      nausea, vomiting and agitation (PONVA). RESULTS: In the examined groups there
      were no statistically significant differences in the duration of anesthesia
      (68.29 +/- 6.47 vs 66.29 +/- 11.97 min, p = 0.327). The time to eye opening was
      significantly shorter in the group VIMA compared to the group TCI (4.49 +/- 1.20
      vs 7.42 +/- 1.25 min, p = 0.000), as well as the time to respond to a command
      (5.93 +/- 1.12 vs 8.47 +/- 1.08 min, p = 0.000). The patients anesthetised with
      VIMA technique wer estatistically significantly extubated earlier (6.84 +/- 1.19
      vs 9.69 +/- 1.31 min, p = 0.000). Considering orientation time, there was also
      statistically significant difference between the two groups (7.51 +/- 0.97 vs
      11.60 +/- 1.75 min, p = 0.000). There was no statistically significant difference
      in PAD time duration (19.42 +/- 5.99 vs 20.80 +/- 1.59 min, p = 0.142). There
      were no statistically significant differences in PONVA events between the
      examined groups. CONCLUSION: This study showed that VIMA technique with
      sevofluran in LC provides faster and more qualitative recovery of patients. Thus
      this technique should be applied in everyday anesthesiological procedures in LC,
      as well as in other minimally invasive videoendoscopic surgical procedures.

PMID- 19583139
TI  - [Breast reconstruction following amputation for cancer].
AB  - BACKGROUND/AIM: Today, breast reconstruction is a widely accepted method in the
      treatment of breast cancer after modified radical mastectomy. Reconstruction
      methods are associated with an acceptable number of complications and
      reconstruction favourably impacts quality of life. The aim of the study was to
      present our experience in breast reconstruction. METHODS: We presented here a
      four-year experience with 84 patients with breast reconstruction after modified
      radical mastectomy. RESULTS: Implant reconstructions were most common, 44
      (52.3%), with primary reconstruction in 31 (70.4%) and secondary in 13 (29.5%)
      women. Lattisimus dorsi flap (LDF) and implant were utilized in 32 (38%) of the
      patients, with primary reconstruction in 24 (75%) and secondary in 8 (25%) women.
      Transversal rectus abdominis myocutaneous (TRAM) flap was rarely used -- just in
      8 (9.5%) patients and only for secondary breast reconstruction. Postoperatively,
      some early complications such as hematoma, seroma, infections and partial flap
      necrosis were observed in 10 (11.9%) patients. Late complications, such as
      implant rejection, hypertrophic scarring and hernias at the flap elevation site,
      were noted in 10 (11.9%) cases. Implant loss occurred in 5 (5.9%) cases. All the
      complications were successfully managed, and patients rated their reconstruction
      as follows: excellent, 49 (59%) cases; very good, 20 (24%), and good, 14 (16.8%).
      In one case, disease progression was observed 6 months after the primary breast
      reconstruction. CONCLUSION: Breast reconstruction is an acceptable method in the
      treatment of breast cancer in patients in the need for or with already performed
      mastectomy. The choice of reconstruction approach depends on the breast volume,
      patient's wish and experience of surgical team. Our results suggest the advantage
      of breast reconstruction with LDF with implant, since the technique is safe,
      complications relatively rare and easily manageable, and the results are
      excellent or very good in each woman.

PMID- 19583140
TI  - Incidence and treatment outcome of oral lichen planus in southeast Serbia in a 10
      year period (1997-2007).
AB  - BACKGROUND/AIM: Lichen planus is a chronic, immunologic, mucocutaneous disease
      with a wide range of clinical manifestations. The aim of this retrospective study
      was to evaluate the most common forms of oral lichen planus (OLP) and its
      symptoms and to describe treatment responses in patients during 10-year period.
      METHODS: The study was conduced on 163 OLP patients who came in the Department of
      Oral medicine and Periodontology between 1997 and September 2007. Each case was
      classified into one of four clinical subtypes: reticular, atrophic, erosive
      ulcerative, bullous. RESULTS: There was no significant difference in patients
      age. Women were found to be significantly more likely to have OLP (p < 0.001).
      Corticosteroids were effective in reducing symptoms, erythema and healing ulcers.
      Improvement was shown over a long term in 61.35% patients. Over the long term
      38.65% patients maintained the same type of OLP or it became a more severe type.
      Two patients (1.22%) developed oral carcinoma during the follow-up period.
      CONCLUSION: The response of patients with erosive OLP to a short course of
      systemic corticosteroids often was quite remarkable. However, symptoms and signs
      tended to recur after this treatment. Periodic examinations, patient education,
      medical treatment, monitoring of side-effects as well as follow-up biopsies are
      necessary for management of OLP patients.

PMID- 19583141
TI  - Clinical significance of vascular endothelial growth factor expression in
      patients with carcinoma of the mouth floor and tongue.
AB  - BACKGROUND/AIM: Although there are several types of malignant oral cancers, more
      than 90% of all diagnosed oral cancers are squamous cell carcinoma (OSCC).
      Angiogenesis is a cascade-like mechanism which is essential for tumor growth and
      metastasis. Therefore, vascular endothelial growth factor (VEGF) expression in
      OSCC and its effect on clinicopathological characteristics and prognosis is of
      major interest. So far researches have shown that increased expression of this
      gene, in other words enhanced sinthesis of this protein (VEGF), independently on
      other factors, increases a chance for local relapse, and distant metastasis.
      Consequently, patients with OSCC have poor disease-free survival, as well as poor
      overall survival. The aim of the study was to determine clinical significance of
      VEGF expression in patients with stage II and III OSCC. METHODS: This
      retrospective study analysed 40 patients who had been operated for OSCC of their
      tongue and the mouth floor. Of these patients, some had stage II and III OSCC
      with histological grade, G1-G3 and nuclear grade Ng1-Ng3. Two high quality tissue
      samples were obtained and immunohistochemical expression of VEGF was
      quantitatively determined by using high microscope amplification. The value of
      VEGF expression of 20% was rated as significant expression, whereas tumor cells
      reactivation less than 20% was considered very low or no expression at all. The
      patients were followed up for a 3-year period. RESULTS: The obtained results
      showed that 11 (17.5%) patients had VEGF expression less than 20% and 29 (82.5%)
      above 20%. A statistical significance was immanent with positive nodal status (p
      < 0.05) and disease stage (p < 0.05). No statistical correlation was found
      between the level of VEGF expression and histological and nuclear grade, tumor
      size, disease relapse or patients overall survival. CONCLUSION: Inspite the
      controversy about the prognostic relevance of VEGF our results as well as the
      results of previous studies, suggest that the expression of VEGF is not reliable
      as a clinical parameter for the prognosis and disease outcome but it is one of
      the important factors for the disease progression.

PMID- 19583142
TI  - [Significance of ligature of early detected insufficient perforated lower
      extremities veins as a cause of the varicose syndrome].
AB  - BACKGROUND/AIM: Perforated veins (PV) connect surface and deep veins net.
      Insufficient perforated veins (IPV) are considered to be one of the causes of the
      venous stasis syndrome. Ligating IPV removes increased pressure transmission from
      the deep veins to the surface veins system and prevents the occurrence of
      varicosis, as well. The aim of the study was to determine surface veins diameters
      prior and after the surgical operation on IPV, and to confirm good results of the
      treatment with this method in removing causes of the surface veins varicosis.
      METHODS: The study included 30 patients of both sexes (25 males and 5 females),
      mean age 30.10 +/- 10.24 years. The patients were classified in accordance with
      CEAP (clinical severity, ethiology or cause, anatomy, pathophysiology)
      classification as those with the initial varicous syndrome based on IPV. Any of
      the patients were submitted to color Doppler echophlebography. In case of
      diameter > or = 3.5 mm PV were marked as IPV. All of the IPV were divided into
      two groups, the group I being with ostium in the stem of Vena Saphena Magna (VSM)
      or Vena Saphena Parva (VSP), while the group II was with ostium in the venous
      tributors. VSM and VSP diameters at the level of IPV ostium, bellow and above (1
      cm) the ostium were measured prior to IPV ligature, and 30 days after the
      surgical intervention. RESULTS: Comparing the results the highest ligature
      effects were shown at the level of IPV ostium in the stem of VSM and VSP of both
      groups (p < 0.0001) with the highest diameter reduction. There was a smaller
      reduction of diameter in the proximal and distal segment of ostium in the group
      I, while there was no diameter change in the distal segment of ostium in the
      group II. CONCLUSION: Saphenous stem diameter reduction at the level of ostium,
      proximally and distally of the confluence, confirms the significance of IPV
      ligature before pronounced varicosis appears.

PMID- 19583143
TI  - [Risk factors for the occurrence of cardiovascular system diseases in students].
AB  - BACKGROUND/AIM: Cardiovascular diseases are a leading cause of death in the
      majority of developed, as well as in many developing countries. The aim of this
      study was to determine cardiovascular risk factors in student population and to
      suggest possible measures for prevention. METHODS: The study was carried out
      during 2007-2008 at the School of Medicine, University of Nis. It included 824
      students in their final year (220 males, 604 females). RESULTS: There was no
      significant difference in prevalence of hypertension among the male (1.81%) and
      female students (0%). The prevalence of obesity (Body Mass Index - BMI > 30
      kg/m2) was significantly higher (p < 0.001) in the male (7.27%) than in the
      female population (1.32%). Abdominal obesity was also more frequently encountered
      (p < 0.01) in the male (9.09%) than in female population (1.32%). Every fourth
      student smoked cigarettes with no significant difference between the male and
      female students. Alcohol consumption was a significantly higher problem (p <
      0.001) in the male population (18.18%) than in the female one (2.65%). Physical
      inactivity was more often found (p < 0.001) in the female students (65.56%), than
      in male ones (36.36%). By the bivariate correlation of cardiovascular risk
      factors, it was determined that in the male student population systolic blood
      pressure correlated significantly with diastolic blood pressure, BMI and waist
      size, whereas age correlated with sistolic blood pressure, waist size and
      smoking. In the female students sistolic blood pressure correlated with diastolic
      blood pressure, BMI and waist size; diastolic blood pressure correlated with BMI
      and physical inactivity; cigarette smoking correlated with alcohol consumption
      and age. CONCLUSION: Cardiovascular risk factors are present in the final-year
      students of the School of Medicine, University of Nis. It is necessary to insist
      on decreasing obesity prevalence, cigarette and alcohol consumption, and on
      increasing physical activity of students in order to prevent cardiovascular
      diseases.

PMID- 19583144
TI  - Clinical evaluation of oxidative stress in patients with diabetes mellitus type
      II -- impact of acute exercise.
AB  - BACKGROUND/AIM: Exercise is a well recognized model of oxidative stress and,
      also, an important tool in diabetes management. The aim of our study was to
      evaluate oxidative stress in patients with diabetes mellitus type 2 and to
      determine influence of acute exercise training on the investigated parameters.
      METHODS: To evaluate oxidative stress in the patients, we determinated following
      parameters: triglycerides (TG), total cholesterol, low density lipoprotein
      cholesterol (LDL), oxidized LDL cholesterol (Ox LDL), superoxide dismutase (SOD),
      glutathione peroxidase (GSHPx), plasminogen activator inhibitor (PAI) which were
      measured at rest and immediately after the acute bout of cardiopulmonary exercise
      cycle-ergometer test. RESULTS: In basal condition, diabetic patients compared to
      controls have significant higher values of TG (3.12 +/- 1.09 vs 1.74 +/- 0.9
      mmol/L, p < 0.01), Ox LDL (84.73 +/- 16.90 vs 79.00 +/- 29.26 mmol/L, p < 0.05)
      and SOD enzyme activity (913.38 +/- 120.36 vs 877.14 +/- 153.18 U/g Hb, p <
      0.05). During the acute exercise test, there was significant increase of Ox LDL
      in both the study patients (from 84.73 +/- 16.90 to 92.33 +/- 23.29 mmol/L, p <
      0.05) and in the control group (from 79.00 +/- 29.26 to 89.30 +/- 29.07 mmol/L, p
      < 0.05). SOD activity was significantly increased in both groups during exercise,
      in diabetic patients from 913.38 +/- 120.36 to 921.50 +/- 130.03 U/gHb, p < 0.05,
      and in the controls from 877.14 +/- 153.18 to 895.00 +/- 193.49, U/gHb, p < 0.05.
      GSH-Px activity was significantly increased only in the diabetic patients after
      the acute exercise (from 45.04 +/- 11.19 to 51.81 +/- 15.07 U/gHb, p < 0.01), but
      not in the controls (from 44.63 +/- 13.73 to 43.97 +/- 25.97 U/gHb, p = ns). PAI
      significantly decreased during the exercise test, only in the healthy subjects
      (from 2.60 +/- 0.35 to 2.22 +/- 0.65, p < 0.05). Type 2 diabetic patients with
      complications had only significant increase in GSH-Px activity (from 47.10 +/-
      7.37 to 54.52 +/- 11.97 U/gHb, p < 0.01). CONCLUSION: Elevated Ox LDL, SOD and
      GSH-Px levels are associated with acute exercise in type 2 diabetic patients. We
      suggest that it could be a compensatory mechanism to preventing free radicals
      tissue damage. We hypothesize that a physical training program induces an enhance
      of muscular and liver antioxidant enzymes activity and reduces oxidative stress.
      Further studies are needed to explore the relationship between exercise and
      antioxidant system in diabetic patients with and without complications.

PMID- 19583145
TI  - [The relationship between C-reactive protein and subclinical carotid
      arteriosclerosis in military pilots].
AB  - BACKGROUND/AIM: Inflammation plays a key role in the physiopathology of
      arteriosclerosis. C-reactive protein (CRP) and common carotid artery intima-media
      thickness are independent predictors of cardiovascular events and diabetes
      mellitus in apparently healthy men, but relationship between them is not fully
      elucidated. The aim of the study was to assess the cross-sectional relationship
      between CRP and cardiovascular risk factors with common carotid artery intima
      media thickness in military pilots as representatives of healthy men. METHODS: We
      studied 161 military pilots (age 38 +/- 6 years) free of cardiovascular disease
      and diabetes mellitus. Traditional and metabolic risk factors were determined.
      Plasma CRP was measured by immunonephelometry. The common carotid artery intima
      media thickness was measured by ultrasonography in the posterior wall of both
      common carotid arteries. RESULTS: A total of 66.5% subjects had common carotid
      artery intima-media thickness > 0.9 mm (p < 0.01). The mean CRP plasma
      concentration was significantly higher in the subjects with common carotid artery
      intima-media thickness > 0.9 mm than in those with common carotid artery intima
      media thickness < or = 0.9 mm. In a simple regression analysis age adjusted CRP
      was associated with common carotid artery intima-media thickness (beta = 0.285, p
      < 0.01), and only high density lipoprotein cholesterol was not associated with
      common carotid artery intima-media thickness. The association between CRP and
      common carotid artery intima-media thickness remained highly significant after
      controlling for body mass index, blood pressure, total cholesterol, low density
      lipoprotein cholesterol, triglycerides, glycosylated hemoglobin and smoking (p <
      0.01). Controlling for glucose, triglycerides to high density lipoprotein
      cholesterol ratio, and total cholesterol to high density lipoprotein cholesterol
      ratio resulted in some reduction in the strength of the association, but
      including waist circumference in the regression made the relationship no longer
      significant (p = 0.119). Body mass index (beta = 0.352; p < 0.01), total
      cholesterol to high density lipoprotein cholesterol ratio (beta = 0.334; p <
      0.01) and age (beta = 0.190; p = 0.036) were the independent predictors of common
      carotid artery intima-media thickness. CONCLUSIONS: In the studied group of
      healthy men CRP per se is not an independent predictor of early arteriosclerosis,
      and may mediate the effect of certain traditional risk factors, especially
      visceral obesity, on promoting aterogenesis.

PMID- 19583146
TI  - Incidence of nasopharyngeal carcinoma in Belgrade during the period 1991-2005.
AB  - BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC) is a relatively rare malignant
      disease, of which 80,000 individuals become ill around the world annually, which
      amounts to 0.7% of all carcinomas. The aim of this descriptive study was to
      analyze NPC incidence in Belgrade (the capital city of Serbia, with about 1.6
      milion inhabitants) during the period 1991-2005. METHODS: In data analysis, crude
      rates age and sex specific rates, and standardized incidence rates were used.
      Standardization was performed by a direct method, using world population as the
      standard. RESULTS: In Belgrade, during the observed 15-year-period, the number of
      new NPC patients totaled 118, of which 86 (72.9%) were male and 32 (27.1%) were
      female. The average standardized incidence rate for men was 0.52 per 100,000 and
      for women 0.16 per 100,000. In both sexes the incidence was very low before 40
      years of age. In men, the greatest incidence rate of NPC was in the 50-59 years
      age group, and in women in those 60 and more years old. Furthermore,
      undifferentiated carcinoma of nasopharyngeal type was 3.6 times more often in
      comparison to squamous cell carcinoma. CONCLUSION: Belgrade belongs to a region
      with a low incidence rate of NPC. Further investigations are needed to explain
      higher frequency of undifferentiated carcinoma of nasopharyngeal type than
      squamous cell carcinoma.

PMID- 19583147
TI  - Fatal diquat intoxication.
AB  - BACKGROUND: Since the introduction of diquat in agriculture practice in 1960's,
      about 40 cases of poisoning have been described in detail in medical literature.
      CASE REPORT: We presented two cases. A case one, a 35-year-old, previously
      healthy, woman ingested 14% diquat solution. The poisoning had fulminant course,
      consisted of severe stomachache, vomiting, cardiocirculatory shock, respiratory
      failure and cardiac arrest 20 hours post-ingestion. Autopsy revealed myocardial
      infarction, bronchopneumonia and incipient renal damage. A case two, a 64-year
      old man developed severe gastroenteritis, corrosive lesions of mucosal surfaces,
      acute renal injury, arrhythmias, brain stem infarction and bronchopneumonia. The
      diagnosis of diquat poisoning was made retrospectively upon the clinical picture
      and identification of pesticides he had been exposed to. The patient died 18 days
      post-exposure. The most prominent findings on autopsy were pontine hemorrhage and
      infarction, bronchopneumonia, left ventricle papillary muscle infarction and
      renal tubular damage. CONCLUSION: Cardiocirculatory disturbances led to fatal
      complications, the heart and brain infarction. We pointed out the heart as one of
      the most severely affected organs in diquat poisoning.

PMID- 19583148
TI  - Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic
      amyloidosis.
AB  - BACKGROUND: Amyloidosis represents a group of different diseases characterized by
      extracellular accumulation of pathologic fibrillar proteins in various tissues
      and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic
      involvement predominantly in the kidney or heart. We evaluated the effect of
      ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of
      different etiologies, who presented with increased alkaline phosphatase and gamma
      glutamyl transferase. CASE REPORT: The study included four patients who presented
      with amyloidosis-associated intrahepatic cholestasis. Three of them had renal
      amyloidosis which developed 1-3 years before cholestasis occurred, the remaining
      one having intrahepatic cholestasis as the primary sign of the disease.
      Amyloidosis was identified from liver biopsies in all patients by its specific
      binding to Congo red and green birefringence in polarized light. The biochemical
      nature and the class of amyloid deposits were identified immunohistochemically.
      In addition to their regular treatment, the patients received 750 mg
      ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant
      decrease of serum alkaline phosphatase and gamma-glutamyl transferase, and their
      general status significantly improved. CONCLUSION: Treatment with ursodeoxycholic
      acid may be beneficial in patients with hepatic amyloidosis, and do extend
      indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver
      disease.

PMID- 19583149
TI  - [Unilatelaral iris plateau syndrome after the use of ecstasy].
AB  - BACKGROUND: Courmon street name for 3,4-Methylenedioxymethamphetamine (MDMA) is
      ecstasy. This widely abused "recreational" drug causes both an increased release
      of monoamine neurotransmitters, including serotonine and dopamine, and an
      increased reuptake inhibition of serotonin. As a consequence, mydriasis and
      increased intraocular pressure (IOP) in predisposed patients occur. We present
      herein a rare case of acute increased IOP after use of ecstasy. CASE REPORT: A
      female patient, aged 38 years, visited doctor complaing of a decreased vision
      acuity and severe pain in the left eye and in the left part of the head. The
      initial treatment was urgent antiglaucomatous therapy followed by withdrawal of
      subjective problems of the patient and improvement of objective finding. History
      taking procedure revaled that just before the onset of the pain the patient had
      used ecstasy and had had similar "experience" 6 years ago after cocaine snorting.
      She had not been to a doctor although she had experienced sporadic migrenous
      pain. Previous medical records excavation of revealed optic disk (cup-to-dise
      C/D=06), Bjerum arcuate scotoma and iris plateau with narrow chamber angle
      (Scheie II-III) so the diagnosis was a rare unilateral iris plateau syndrome of
      the left eye. Although the patient was given some pieces of information about the
      dangerous and possible deadly consequences of psychoactive substanace abuse, she
      has not continue the treatment. CONCLUSION: Ecstasy abuse might cause a complete
      loss of vision, thus medicametous and surgical treatment are abligatory.

PMID- 19583150
TI  - [Medicine in Rembrant's works].

PMID- 19583151
TI  - Coarse particulate matter apportionment around a steel smelter plant.
AB  - The results from a study carried out in the urban area of Genoa, Italy, where a
      large steel smelter recently shut down are presented. We had the opportunity to
      sample particulate matter (PM) before and after plant closure and, therefore, to
      measure the changes in concentration and composition of PM10 (atmospheric PM with
      aerodynamic diameter <10 microm). Elemental concentrations of Na to Pb were
      obtained through energy dispersive X-ray fluorescence (ED-XRF), and the
      contributions of specific sources of PM10 were calculated by positive matrix
      factorization (PMF). The PM10 average concentration turned out to be surprisingly
      similar before and after closing of the smelter. Nevertheless, the comparison
      among data collected in the two periods (plant operating and closed), even with
      the limited information provided by ED-XRF, allowed us to single out two sources
      of PM related to the smelter activities, to extract their emission profile, and
      to quantify the impact of the plant on PM10 levels.

PMID- 19583153
TI  - Extractive sampling and optical remote sensing of F100 aircraft engine emissions.
AB  - The Strategic Environmental Research and Development Program (SERDP) has
      initiated several programs to develop and evaluate techniques to characterize
      emissions from military aircraft to meet increasingly stringent regulatory
      requirements. This paper describes the results of a recent field study using
      extractive and optical remote sensing (ORS) techniques to measure emissions from
      six F-15 fighter aircraft. Testing was performed between November 14 and 16, 2006
      on the trim-pad facility at Tyndall Air Force Base in Panama City, FL.
      Measurements were made on eight different F100 engines, and the engines were
      tested on-wing of in-use aircraft. A total of 39 test runs were performed at
      engine power levels that ranged from idle to military power. The approach adopted
      for these tests involved extractive sampling with collocated ORS measurements at
      a distance of approximately 20-25 nozzle diameters downstream of the engine exit
      plane. The emission indices calculated for carbon dioxide, carbon monoxide,
      nitric oxide, and several volatile organic compounds showed very good agreement
      when comparing the extractive and ORS sampling methods.

PMID- 19583152
TI  - Evaluation of wood chip-based biofilters to reduce odor, hydrogen sulfide, and
      ammonia from swine barn ventilation air.
AB  - A pilot-scale biofilter was developed in which two types of wood chips (western
      cedar [WC] and 2-in. hardwood [HW]) were examined to treat odor emissions from a
      deep-pit swine finishing facility in central Iowa. The biofilters were operated
      continuously for 13 weeks at different airflow rates resulting in variable empty
      bed residence times (EBRTs) from 1.6 to 7.3 sec. The effects of three media
      moisture levels were also evaluated. A dynamic forced-choice olfactometer was
      used to evaluate odor concentrations from both the control (inlet) plenum and
      biofilter treatments (outlet). Hydrogen sulfide (H2S) and ammonia (NH3)
      concentrations were also measured from these olfactometry samples. Solid-phase
      microextraction (SPME) polydimethylsiloxane (PDMS)/divinylbenzene (DVB) 65-microm
      fibers were used to extract volatile organic compounds from both the control
      plenum and biofilter treatments. Analyses of separated odors were carried out
      using a gas chromatography-mass spectrometry-olfactometry (GC-MS-O) system.
      Static sample results indicated that both types of chips achieved significant
      reductions in odor (average 70.1 and 82.3% for HW and WC, respectively), H2S
      (average 81.8 and 88.6% for HW and WC, respectively) and NH3 (average 43.4 and
      74% for HW and WC, respectively) concentrations. GC-MS-O aromagram results showed
      both treatments reached high odor reduction efficiency (average 99.4 and 99.8%
      for HW and WC, respectively). The results also showed that maintaining proper
      moisture content and a minimum EBRT are critical to the success of wood chip
      based biofilters.

PMID- 19583154
TI  - Evaluation of bioaerosol components, generation factors, and airborne transport
      associated with lime treatment of contaminated sediment.
AB  - Lime treatment has been used in contaminated sediment management activities for
      many purposes such as dewatering, improvement of physical properties, and
      reducing contaminant mobility. Exothermic volatilization of volatile organic
      compounds from lime-treated sediment is well known, but potential aerosolization
      of bioaerosol components has not been evaluated. A physical model of a
      contaminated sediment treatment and airborne transport process and an
      experimental protocol were developed to identify specific bioaerosol components
      (bacteria, fungi, cell structural components, and particles) that may be
      aerosolized and transported. Key reaction variables (amount of lime addition,
      rate of lime addition, mixing energy supplied) that may affect the aerosolization
      of bioaerosol components were evaluated. Lime treatment of a sediment
      contaminated with heavy metals, petroleum-based organics, and microorganisms
      increased the sediment pH and solids content. Lime treatment reduced the number
      of water-extractable bacteria and fungi in the sediment from approximately 10(6)
      colony-forming units (CFU) x mL(-1) to less than the detection limit of 10(3) CFU
      x mL(-1). This reduction was seen immediately for bacteria and within 21 days for
      fungi. Lime treatment immediately reduced the amount of endotoxin in the
      sediment, but the effects of lime treatment on beta-D-glucan could not be
      determined. The temperature of the treated sediment was linearly related to the
      amount of lime added within the range of 0-25%. Bacteria were aerosolized during
      the treatment trials, but there was no culturable evidence of aerosolization of
      fungi, most likely because of either their particular growth stage or relatively
      larger particle size that reduced their aerosolization potential and their
      collection into the impingers. Nonbiological particles, endotoxin, and beta-D
      glucan were not detected in air samples during the treatment trials. The amount
      of lime added to the reaction beaker and the relative amount of mixing energy
      supplied to the reaction significantly affected the aerosolization ratio of
      bacteria (amount of aerosolized bacteria divided by the amount of bacteria in
      untreated sediment) from the reaction beaker. The rate of lime addition did not
      significantly affect the aerosolization ratio of bacteria. The aerosolization
      results suggest that exposure to bacteria is possible with sediment treatment
      activities, but the hazard level could not be determined because speciation of
      the aerosolized bacteria for pathogen identification was not performed, and
      health and safety standards and criteria for bioaerosol components have not been
      developed. Quantitative scaling analysis and whether the system represents actual
      environmental conditions were not studied.

PMID- 19583155
TI  - Measurement and capture of fine and ultrafine particles from a pilot-scale
      pulverized coal combustor with an electrostatic precipitator.
AB  - Experiments were carried out in a pilot-scale pulverized coal combustor at the
      Energy and Environmental Research Center (EERC) burning a Powder River Basin
      (PRB) subbituminous coal. A scanning mobility particle sizer (SMPS) and an
      electrical low-pressure impactor (ELPI) were used to measure the particle size
      distributions (PSDs) in the range of 17 nm to 10 microm at the inlet and outlet
      of the electrostatic precipitator (ESP). At the ESP inlet, a high number
      concentration of ultrafine particles was found, with the peak at approximately 75
      nm. A trimodal PSD for mass concentration was observed with the modes at
      approximately 80-100 nm, 1-2 microm, and 10 microm. The penetration of ultrafine
      particles through the ESP increased dramatically as particle size decreased below
      70 nm, attributable to insufficient or partial charging of the ultrafine
      particles. Injection of nanostructured fine-particle sorbents for capture of
      toxic metals in the flue gas caused high penetration of the ultrafine particles
      through the ESP. The conventional ESP was modified to enhance charging using soft
      X-ray irradiation. A slipstream of flue gas was introduced from the pilot-scale
      facility and passed through this modified ESP. Enhancement of particle capture
      was observed with the soft X-ray irradiation when moderate voltages were used in
      the ESP, indicating more efficient charging of fine particles.

PMID- 19583156
TI  - Energy recycling by co-combustion of coal and recovered paint solids from
      automobile paint operations.
AB  - During the past decade, there has been substantial interest in recovering energy
      from many unwanted byproducts from industries and municipalities. Co-combustion
      of these products with coal seems to be the most cost-effective approach. The
      combustion process typically results in emissions of pollutants, especially fine
      particles and trace elements. This paper presents the results of an experimental
      study of particulate emission and the fate of 13 trace elements (arsenic [As],
      barium [Ba], cadmium [Cd], chromium [Cr], copper [Cu], cobalt [Co], manganese
      [Mn], molybdenum [Mo], nickel [Ni], lead [Pb], mercury [Hg], vanadium [V], and
      zinc [Zn]) during combustion tests of recovered paint solids (RPS) and coal. The
      emissions from combustions of coal or RPS alone were compared with those of co
      combustion of RPS with subbituminous coal. The distribution/partitioning of these
      toxic elements between a coarse-mode ash (particle diameter [dp] > 0.5 microm), a
      submicrometer-mode ash (dp < 0.5 microm), and flue gases was also evaluated.
      Submicrometer particles generated by combustion of RPS alone were lower in
      concentration and smaller in size than that from combustion of coal. However, co
      combustion of RPS and coal increased the formation of submicrometer-sized
      particles because of the higher reducing environment in the vicinity of burning
      particles and the higher volatile chlorine species. Hg was completely volatilized
      in all cases; however, the fraction in the oxidized state increased with co
      combustion. Most trace elements, except Zn, were retained in ash during
      combustion of RPS alone. Mo was mostly retained in all samples. The behavior of
      elements, except Mn and Mo, varied depending on the fuel samples. As, Ba, Cr, Co,
      Cu, and Pb were vaporized to a greater extent from cocombustion of RPS and coal
      than from combustion of either fuel. Evidence of the enrichment of certain toxic
      elements in submicrometer particles has also been observed for As, Cd, Cr, Cu,
      and Ni during co-combustion.

PMID- 19583157
TI  - Biofiltration of air contaminated by styrene vapors on inorganic filtering media:
      an experimental study.
AB  - This paper presents a study on the biofiltration of styrene by using two
      inorganic filtering materials. The effects of styrene inlet load and nitrogen
      concentration present in the nutrient solution on biofilter performance were
      studied. The styrene inlet concentration was varied from 65 to 1115 parts per
      million by volume (ppmv), whereas the contaminated airflow rate was fixed at 1
      m3/hr. The nitrogen concentration in nutrient solution was varied from 1 to 4
      gN/L. The maximum elimination capacity obtained was 105 g/m3-hr, which
      corresponded to a removal efficiency of 80% for a styrene inlet load of 130 g/m3
      hr. This study shows that the nitrogen content in the nutrient solution affects
      the removal rate of styrene, with an optimal nitrogen concentration of 3 gN/L.
      The performance comparison between two different inorganic bed types was
      undertaken and a comparative study on biofiltration of two aromatic compounds,
      styrene and toluene, is also presented.

PMID- 19583158
TI  - The national ambient air monitoring strategy: rethinking the role of national
      networks.
AB  - A current re-engineering of the United States routine ambient monitoring networks
      intended to improve the balance in addressing both regulatory and scientific
      objectives is addressed in this paper. Key attributes of these network
      modifications include the addition of collocated instruments to produce multiple
      pollutant characterizations across a range of representative urban and rural
      locations in a new network referred to as the National Core Monitoring Network
      (NCore). The NCore parameters include carbon monoxide (CO), sulfur dioxide (SO2),
      reactive nitrogen (NOy), ozone (O3), and ammonia (NH3) gases and the major fine
      particulate matter (PM2.5) aerosol components (ions, elemental and organic carbon
      fractions, and trace metals). The addition of trace gas instruments, deployed at
      existing chemical speciation sites and designed to capture concentrations well
      below levels of national air quality standards, is intended to support both long
      term epidemiological studies and regional-scale air quality model evaluation. In
      addition to designing the multiple pollutant NCore network, steps were taken to
      assess the current networks on the basis of spatial coverage and redundancy
      criteria, and mechanisms were developed to facilitate incorporation of
      continuously operating particulate matter instruments.

PMID- 19583159
TI  - The social distribution of neighborhood-scale air pollution and monitoring
      protection.
AB  - The potential for inequities between population subgroups in air pollution
      exposures and in regulatory protection because of small-scale intraurban
      differences in outdoor air pollution and air quality monitoring are studied here.
      The focus subgroups are blacks, Hispanics, whites, and the population living
      below poverty, with Tampa, FL, used as the case study area for quantitative
      analyses. A geographical database is developed for the surrounding county that
      includes population demographics, source locations, monitor locations, and air
      pollutant concentrations. Data included are residential population demographics
      at the block-group spatial scale from the year 2000 U.S. Census, U.S.
      Environmental Protection Agency (EPA) Toxic Releases Inventory source locations
      and air source release amounts, EPA Air Quality System monitoring data, and
      Florida major highway source locations and roadway traffic data. This database is
      applied for analysis of the spatial relationships between residence locations of
      population subgroups and outdoor air pollution surrogates. A quantitative index
      to evaluate the inequity between subpopulations is developed and applied.
      Findings include that blacks, Hispanics, and people living in poverty are
      disproportionately living closer to sources of air pollution and further from
      regulatory air quality monitoring sites compared with the overall county
      population. Conversely, whites are disproportionately living away from sources
      and near monitoring sites. Analysis of the regulatory monitoring guidelines
      indicates that recent changes in those guidelines may exacerbate existent
      inequities. The results suggest disparities in exposures to air pollution,
      disparities in regulatory monitoring representation, and the need for more
      monitoring and analyses at smaller spatial scales.

PMID- 19583160
TI  - A new technique for characterizing the efficacy of fugitive dust suppressants.
AB  - The Portable In-Situ Wind Erosion Laboratory (PI-SWERL) instrument was evaluated
      for testing the effectiveness of dust suppressants for a range of native and
      constructed soils. The PM10 (particles with diameter < or = 10 microm) emissions
      from dust suppressant-treated and untreated soil surfaces were measured
      periodically over 14 months. No statistically significant differences were found
      among soil surfaces treated with three dilution mixtures of the dust suppressant.
      The temporal variation of PM10 emissions from treated and untreated plots for
      native and constructed soil textures indicated that: (1) reductions of PM10
      emissions by the dust suppressant were significant within 2-3 months after the
      application and diminished substantially thereafter, (2) decomposition of the
      protective treated layer resulted in high PM10 emissions for longer environmental
      exposure times, and (3) emissions from untreated soil surfaces declined over time
      because of the formation of a natural crust. These results demonstrated that the
      PI-SWERL can provide qualitative and quantitative information on PM10 emissions
      for a range of soil textures and can be used to estimate the effectiveness of
      dust suppressants exposed to actual environmental (i.e., weather and solar
      radiation) conditions over long periods of time.

PMID- 19583161
TI  - Seasonal ammonia emissions from a free-stall dairy in central Texas.
AB  - Studies show that agricultural and animal feeding operations (AFOs) contribute a
      considerable amount of ammonia (NH3) to the atmosphere. Agricultural NH3
      emissions are recognized as an important air quality issue. Biological
      decomposition of manure from dairy operations results in emissions of NH3 and
      other gases. There is a need to determine NH3 emission factors (EFs) to compile
      annual NH3 inventories. NH3 emissions should be estimated from different ground
      level area sources (GLAS) including open-lots (cows on earthen corrals), free
      stalls (cows in barns), manure composting sites, primary and secondary lagoons,
      separated solids, and milking parlors. A protocol using flux chambers was used to
      determine NH3 EFs from different GLAS of a free-stall dairy in central Texas.
      Data including NH3 emissions from GLAS were collected during winter and summer
      seasons. NH3 concentration measurements were made using chemiluminescence-based
      analyzers. The EFs for the free-stall dairy were estimated as 11 +/- 4.9
      (confidence interval [CI]) kg-NH3 x yr(-1) x head(-1) for summer and 4.7 +/- 4.9
      kg-NH3 x yr(-1) x head(-1) for winter. The estimated annual NH3 EF was 8.4 +/-
      4.9 kg-NH3 x yr(-1) head(-1) for this free-stall dairy. This seasonal difference
      was attributed to temperature, loading rate of dairy waste, and manure bacterial
      activity of GLAS. In winter, composted manure and free-stalls contributed nearly
      77% of the total NH3 emissions for the dairy; however, in summer, two lagoons at
      the dairy contributed 65% of the overall NH3 emissions.

PMID- 19583162
TI  - Development of welding emission factors for Cr and Cr(VI) with a confidence
      level.
AB  - Knowledge of the emission rate and release characteristics is necessary for
      estimating pollutant fate and transport. Because emission measurements at a
      facility's fence line are generally not readily available, environmental agencies
      in many countries are using emission factors (EFs) to indicate the quantity of
      certain pollutants released into the atmosphere from operations such as welding.
      The amount of fumes and metals generated from a welding process is dependent on
      many parameters, such as electrode composition, voltage, and current. Because
      test reports on fume generation provide different levels of detail, a common
      approach was used to give a test report a quality rating on the basis of several
      highly subjective criteria; however, weighted average EFs generated in this way
      are not meant to reflect data precision or to be used for a refined risk
      analysis. The 95% upper confidence limit (UCL) of the unknown population mean was
      used in this study to account for the uncertainty in the EF test data. Several
      parametric UCLs were computed and compared for multiple welding EFs associated
      with several mild, stainless, and alloy steels. Also, several nonparametric
      statistical methods, including several bootstrap procedures, were used to compute
      95% UCLs. For the nonparametric methods, a distribution for calculating the mean,
      standard deviation, and other statistical parameters for a dataset does not need
      to be assumed. There were instances when the sample size was small and instances
      when EFs for an electrode/process combination were not found. Those two points
      are addressed in this paper. Finally, this paper is an attempt to deal with the
      uncertainty in the value of a mean EF for an electrode/process combination that
      is based on test data from several laboratories. Welding EFs developed with a
      defined level of confidence may be used as input parameters for risk assessment.

PMID- 19583163
TI  - The hazards of alternative care.

PMID- 19583164
TI  - A visual essay. Aesthetic enhancement of the anterior maxilla using a pressed
      ceramic fabrication technique.

PMID- 19583165
TI  - Restorations of endodontically treated teeth: new concepts, materials, and
      aesthetics.
AB  - The care of endodontically treated teeth has been one of the greatest challenges
      in restorative dentistry. Left unrestored, endodontically treated teeth have
      complications that include coronal leakage and subsequent reinfection of the root
      canal system. These teeth are at risk for fracture, since they become predisposed
      to structural compromise when compared to their properly restored counterparts.
      As demonstrated herein, caries, previous restorations, fractures, wear, erosion,
      and endodontic procedures each require careful consideration and timely tooth
      reconstruction to ensure a favorable prognosis.

PMID- 19583166
TI  - The evolving e-practice. In-office digital dentistry: cutting-edge technologies
      for impression capture, restorative design, and prosthesis fabrication.

PMID- 19583167
TI  - Minimally invasive dentistry: paradigm shifts in preparation design.
AB  - While the concept of minimally invasive dentistry has long been considered a
      rational, viable approach to restorative care, preparation design, material
      science, and long-term evidentiary support have only recently begun to provide
      the foundation necessary to support such treatment in the everyday practice. This
      article reviews the fundamental paradigm shift evidenced in contemporary
      prosthodontics as required to facilitate the emerging interest in delivering
      conservative restorative alternatives.

PMID- 19583168
TI  - Communicating patient care for oral irritations and ulcerations.

PMID- 19583169
TI  - Impression-free/model-free anterior fixed partial denture: a novel CAD/CAM
      approach.

PMID- 19583170
TI  - A visual essay. Correction of asymmetry via laser gingivectomy, implant
      placement, and fixed restorations.

PMID- 19583172
TI  - What is the role of the registered nurse?

PMID- 19583171
TI  - Developing enhanced aesthetics: a laboratory approach to restoration of
      compromised dentition in the anterior region.
AB  - The artistry involved in the development of natural-looking, aesthetic
      restorations has been recognized by dental professionals and patients alike,
      increasing the role of the laboratory technician in the overall treatment
      planning phase. While it is rare for patients to first present to the laboratory
      for treatment, proactive technicians can actively seek out patients and assist
      them in identifying the type of restorative care desired and provide a reference
      to a qualified clinician once a modality has been identified. The following case
      presentation details the laboratory sequence used in the fabrication of a low
      fusing pressed ceramic restoration for a patient who presented to the laboratory
      for initial consultation and treatment planning.

PMID- 19583173
TI  - Leveraging the role of public health nursing in managing HIV/AIDS in Thailand: a
      journey of international collaboration.
AB  - Thailand is one of the first countries to have achieved significant advances in
      control over the HIV/AIDS epidemic occurring within its borders. Despite this
      impressive accomplishment, the disease continues to be a Leading cause of death
      in Thailand and is migrating into Thai populations heretofore relatively free of
      it, such as married women. In 2003, a unique Thai, American, academic, and
      government collaboration formed to address the on-going challenges of HIV/AIDS in
      Thailand and its emerging characteristics. The objective of this collaboration
      was to increase the capacity of Thailand's public health infrastructure to
      address the challenges of HIV/AIDS by utilizing a Larger and more empowered role
      for nurses within the country's existing health care system. This collaboration
      consisted of the Deans' Consortium of Nursing Educational Institutions, the Thai
      Ministry of Public Health, the Faculty of Nursing at Mahidol University, and
      United States university nursing educators. This paper describes the process that
      brought this collaboration into being. It also describes the outcomes achieved by
      this collaboration; a collaboration that realized a national strategy to Leverage
      and expand the role of public health nurses and the initiation of a nurse
      practitioners' role in the prevention and treatment of HIV/AIDS. This
      collaboration and strategy increased the capacity of the health care system in
      Thailand to more effectively meet the challenges posed by all infectious diseases
      in Thailand and, in particular, HIV/AIDS.

PMID- 19583174
TI  - Advanced nursing practice: a global perspective.
AB  - AIM: To review the titles, roles and scope of practice of Advanced Practice
      Nurses internationally. BACKGROUND: There is a worldwide shortage of nurses but
      there is also an increased demand for nurses with enhanced skills who can manage
      a more diverse, complex and acutely ill patient population than ever before. As a
      result, a variety of nurses in advanced practice positions has evolved around the
      world. The differences in nomenclature have led to confusion over the roles,
      scope of practice and professional boundaries of nurses in an international
      context. METHOD: CINAHL, Medline, and the Cochrane database of Systematic Reviews
      were searched from 1987 to 2008. Information was also obtained through government
      health and professional organisation websites. All information in the literature
      regarding current and past status, and nomenclature of advanced practice nursing
      was considered relevant. FINDINGS: There are many names for Advanced Practice
      Nurses, and although many of these roles are similar in their function, they can
      often have different titles. CONCLUSION: Advanced Practice Nurses are critical
      for the future, provide cost-effective care and are highly regarded by
      patients/clients. They will be a constant and permanent feature of future health
      care provision. However, clarification regarding their classification and
      regulation is necessary in some countries.

PMID- 19583175
TI  - The spectrum of 'new racism' and discrimination in hospital contexts: a
      reappraisal.
AB  - In keeping with the United Nations Declaration of Human Rights, all people have
      the right to the highest attainable standard of health. Despite the universal
      right to health, people of minority racial and ethnic backgrounds experience
      commonplace and significant unjust inequalities in their health and health care.
      A key reason for this rests on what might be described as 'the illusion of non
      racism in health care' -- an illusion that rests on the frequently articulated
      belief that 'racism is not an issue any more'. Although there has been increasing
      recognition in recent years that race and racism have a particular, consistent
      and complex independent negative effect on the health and health care of racial
      and ethnic minority groups, racism per se still tends to be under-recognised and
      poorly addressed in health and nursing care domains. In this paper, it is
      suggested that a key reason racism in health care has been Largely ignored is
      because of its 'changing face', making new and different forms of it difficult to
      recognise and manage. A key premise on which this paper rests -- and also its
      ultimate conclusion -- is that the problem of racism (to be distinguished from
      'culturally insensitive' and 'culturally incongruent' care) needs to be unmasked
      and managed so that those most at risk of being discriminated against on
      racialised grounds can rest assured that when in need, they will receive the
      equitable, safe and quality care they are entitled to receive.

PMID- 19583176
TI  - Internal conflict: undergraduate nursing students' response to inadequate
      supervision during the administration of medication.
AB  - Current legislation in Queensland requires that undergraduate nursing students
      are personally supervised when administering restricted medication in the
      clinical setting. Previous research suggests this is not always the case.
      Exploration of the experiences of undergraduate nursing students was undertaken
      using grounded theory as the methodological framework. In-depth, semi-structured
      interviews were conducted with 28 students during their final year clinical
      placements. Data were analysed using a constant comparative approach. The focus
      of this paper is to examine the emergent theme of internal conflict, which is
      experienced by the participants as a consequence of the theory-practice gap. This
      conflict is reflected by the divergent requirements and expectations between the
      university and the registered nurses providing supervision in light of the role
      both play in student assessment. In addition, the participants voiced concerns
      about patient safety due to the potential for medication error. Internal conflict
      was identified by participants as the cause of considerable fear and anxiety
      about passing the course, getting a job and avoiding harm to patients. These
      findings raise serious concerns about the adequacy of the supervision for nursing
      students and highlighted the need for a more concerted approach to the
      theoretical and clinical education of students in relation to medication
      administration.

PMID- 19583177
TI  - Preferences for continuing education through existing electronic access for
      Australian nurse practitioners and its implication in prescribing potential.
AB  - BACKGROUND: Little is known about Australian Nurse Practitioners (NPs)
      perceptions of the importance of continuing education (CE), their preferred
      methods to undertake CE in relation to prescribing practices or their access to
      electronic resources at work. Nurse Practitioner access to computerised
      technology may increase their provision of resources, provide point of care
      technology, and increase opportunities to participate in CE. PURPOSE: This paper
      aims to explore Australian NP preferences for continuing education and NP access
      to electronic mediums that may increase CE opportunities. METHODS: A self
      administered online survey was completed by 68 NPs from across Australia.
      RESULTS: The majority of respondents (93%) viewed CE to be very important and
      preferred methods of continuing education included receipt of information by
      email, and interactive online case studies. Respondents working in metropolitan
      areas had increased access to high speed Internet in comparison to NPs working in
      rural or remote areas, although this did not reach statistical significance (88%
      vs. 69%, p = 0.07). Significantly more NPs working in metropolitan areas had
      access to a Personal Digital Assistant (PDA) than NPs working in rural or remote
      areas (44% vs. 6%, p = 0.003). CONCLUSION: This is the first national survey to
      report preference for CE and access to technology of NPs in Australia. Electronic
      technology can provide programmed support such as online learning and resources
      through computers and PDAs to maximise NP prescribing potential.

PMID- 19583178
TI  - How do CNCs construct their after hours support role in a major metropolitan
      hospital.
AB  - AIM: To explore how CNCs who provide hospital wide support after hours (AHCSs)
      construct their role. METHODS: This is an ethnographic study involving two AHCSs
      as participants. Audio visual data was collected in 2007 at a Major Metropolitan
      Hospital, Sydney during after hours shifts. The data was coded using the
      standards defined in the Nurse Practitioner (NP) competencies. RESULTS: Four
      hours of videotape (observed clinical practice) and 2 h of audio tape
      (interviews) were coded. They performed procedures (22%), gathered information to
      identify at risk patients (21%), conducted patient assessments (20%) and relayed
      information/findings to ward nurses (12%) and doctors (12%). The
      roles/responsibilities of AHCSs were similar to those defined for NPs. For the
      domain "dynamic practice" 388 activities were identified. The two participants
      used advanced and comprehensive assessment skills and demonstrated a high level
      of proficiency in performing procedures/interventions. For the domain
      "professional efficacy" 174 activities were coded, for "clinical Leadership"
      there were 135 activities. "Pro-actively identifying at risk patients in general
      wards" was added as a new performance indicator within the domain "clinical
      leadership". An analysis of the interviews corroborated the results derived from
      the visual data. CONCLUSION: A significant capacity for critical thinking and
      clinical decision making were the hallmarks of the performance of the two AHCSs;
      their style of practice was collaborative, flexible and autonomous. While their
      formal role were as CNCs the two participants operationalised their
      roles/responsibilities as would a Nurse Practitioner. Their practice demonstrated
      a new competency: "the pro-active identification of at risk patients".

PMID- 19583179
TI  - Direct electron transfer to a metalloenzyme redox center coordinated to a
      monolayer-protected cluster.
AB  - A strategy for establishing electrical contact to the metal center of a redox
      metalloenzyme, galactose oxidase (GOase), by coordination of a linker attached to
      a monolayer-protected gold cluster is presented. The cluster-enzyme hybrid system
      was first prepared in solution and characterized by high-angle annular dark-field
      scanning transmission electron microscopy. Electrochemical communication between
      a gold electrode and GOase was achieved by first modifying the electrode surface
      with a biphenyl dithiol self-assembled monolayer followed by reaction with gold
      clusters capped with thioctic acid. GOase was then immobilized by replacement of
      the H(2)O molecule at the Cu(II) exogenous site by coordination of a carboxylate
      terminated gold cluster. This chemical attachment ensured electrical contact
      between the redox center and the electrode, leading to direct mediatorless
      electron transfer to the protein. Hybrid systems can find applications in
      biosensors and biofuel cells and for studying electrochemically the catalytic
      mechanism of reactions for which free radicals and electron-transfer reactions
      are involved. The present results can be extended to other metalloenzymes.

PMID- 19583180
TI  - Dynamic interfacial tension measurements with microfluidic Y-junctions.
AB  - Emulsification in microdevices (microfluidic emulsification) involves micrometer
      sized droplets and fast interface expansion rates. In addition, droplets are
      formed in less than milliseconds, and therefore traditional tensiometric
      techniques cannot be used to quantify the actual interfacial tension. In this
      paper, monodisperse droplets formed at flat microfluidic Y-junctions were used to
      quantify the apparent dynamic interfacial tension during (microfluidic)
      emulsification. Hexadecane droplets were formed in ethanol-water solutions with a
      range of static interfacial tensions to derive a calibration curve, which was
      subsequently used to access the dynamic interfacial tension of hexadecane
      droplets formed in surfactant solutions. For SDS and Synperonic PEF108, various
      continuous- and disperse-phase (hexadecane) flow rates were studied, and these
      conditions were linked to interfacial tension effects, which also allowed
      convective transport of surfactants to be investiagted. On the basis of these
      findings, various strategies for the formation of emulsion droplets can be
      followed and are discussed.

PMID- 19583181
TI  - Cadherin and integrin regulation of epithelial cell migration.
AB  - These studies quantified the relative effects of E-cadherin expression and
      homophilic ligation on the integrin-mediated motility of epithelial cells.
      Micropatterned proteins were used to quantitatively titrate the ligation of E
      cadherin and integrin receptors in order to assess their coordinate influence on
      the migration velocities of MDA-MB-231 breast tumor epithelial cells.
      Fibronectin, E-cadherin, and mixtures of fibronectin and E-cadherin were
      covalently patterned on solid surfaces at defined compositions and mass
      coverages. The migration velocities of parental epithelial cells and of cells
      engineered to express E-cadherin under tetracycline control show that E-cadherin
      expression reduces cell motility by both adhesion-dependent and adhesion
      independent mechanisms. Increasing E-cadherin expression levels also suppresses
      the dependence of cell velocity on the fibronectin coverage. On E-cadherin
      containing substrata, the cell velocity decreases both with the E-cadherin
      expression level and with the immobilized E-cadherin surface density. These
      studies thus identified conditions under which E-cadherin preferentially
      suppresses cell migration by adhesion-independent versus adhesion-dependent
      mechanisms.

PMID- 19583182
TI  - Fabrication and luminescence properties of one-dimensional CaMoO(4): Ln(3+) (Ln =
      Eu, Tb, Dy) nanofibers via electrospinning process.
AB  - One-dimensional CaMoO(4):Ln(3+) (Ln = Eu, Tb, Dy) nanofibers have been prepared
      by a combination method of sol-gel and electrospinning process. X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), high-resolution
      transmission electron microscopy (HRTEM), photoluminescence (PL), and low voltage
      cathodoluminescence (CL) as well as kinetic decays were used to characterize the
      resulting samples. SEM and TEM analyses indicate that the obtained precursor
      fibers have a uniform size, and the as-formed CaMoO(4):Ln(3+) nanofibers consist
      of nanoparticles. Under ultraviolet excitation, the CaMoO(4) samples exhibit a
      blue-green emission band with a maximum at 500 nm originating from the MoO(4)(2-)
      groups. Due to an efficient energy transfer from molybdate groups to dopants,
      CaMoO(4):Ln(3+) phosphors show their strong characteristic emission under
      ultraviolet excitation and low-voltage electron beam excitation. The energy
      transfer process was further studied by the emission spectra and the kinetic
      decay curves of Ln(3+) upon excitation into the MoO(4)(2-) groups in the
      CaMoO(4):x mol % Ln(3+) samples (x = 0-5). Furthermore, the emission colors of
      CaMoO(4):Ln(3+) nanofibers can be tuned from blue-green to green, yellow, and
      orange-red easily by changing the doping concentrations (x) of Ln(3+) ions,
      making the materials have potential applications in fluorescent lamps and field
      emission displays (FEDs).

PMID- 19583183
TI  - Pursuing "zero" protein adsorption of poly(carboxybetaine) from undiluted blood
      serum and plasma.
AB  - Human blood serum and plasma pose significant challenges to blood-contacting
      devices and implanted materials because of their high nonspecific adsorption onto
      surfaces. In this work, we investigated nonspecific protein adsorption from
      single protein solutions and complex media such as undiluted human blood serum
      and plasma onto poly(carboxybetaine acrylamide) (polyCBAA)-grafted surfaces at
      different temperatures. The polyCBAA grafting was done via atom-transfer radical
      polymerization (ATRP) with varying film thicknesses. The objective is to create a
      surface that experiences "zero" protein adsorption from complex undiluted human
      blood serum and plasma. Results show that protein adsorption from undiluted human
      blood serum, plasma, and aged serum on the polyCBAA-grafted surface is
      undetectable at both 25 and 37 degrees C by a surface plasmon resonance (SPR)
      sensor. This was achieved with a film thickness of approximately 21 nm.
      Furthermore, it is demonstrated that the polyCBAA surfaces after antibody
      immobilization maintain undetectable protein adsorption from undiluted human
      blood serum. This is the first time that an effective nonfouling material
      suitable for applications in complex blood media has been demonstrated.

PMID- 19583184
TI  - Etching-resistant silver nanoprisms by epitaxial deposition of a protecting layer
      of gold at the edges.
AB  - The protection of silver nanoprisms against etching by the epitaxial deposition
      of a thin layer of gold in solution has been investigated. It has been found that
      at low Au/Ag ratios (approximately 0.08 to 0.17) a thin layer of gold is
      deposited on the edges of the nanoprisms as expected, but without the structural
      damage typically associated with galvanic replacement. Furthermore, this layer of
      gold provides robust protection against etching of the nanoprisms by chloride and
      is strong evidence that etching by chloride is face-selective and does not take
      place at the flat {111} faces of the nanoprisms. Additionally, the deposition of
      a protecting layer of gold results in only a small red shift in the position of
      the main plasmon resonance. We have investigated the sensitivity of the localized
      surface plasmon resonance (LSPR) to changes in the bulk refractive index of the
      solution and find that the gold-protected silver nanoprisms are promising
      candidates for the development of new refractive index-based biosensors.

PMID- 19583186
TI  - Synthesis of colloidal particles with the symmetry of water molecules.
AB  - We describe a method for synthesizing "colloidal water": monodisperse micrometer
      sized polymer particles with the symmetry of water molecules. Our approach is
      based on multistep seeded polymerization with variation of cross-linker
      concentration in each step. This enables precise control of swelling selectivity
      and phase-separation, which control the particle morphology.

PMID- 19583187
TI  - Collective diffusion in colloid-polymer suspensions: relative role of
      thermodynamics and hydrodynamics.
AB  - Theories such as the mode coupling theory (MCT) have seen recent success in
      predicting the kinetic arrest boundaries and resultant flow properties of
      colloidal suspensions. A key assumption of such theories is that interparticle
      forces and equilibrium structure control slow dynamics and gelation, not long
      time many-body hydrodynamics. Here we report measurements of short-time
      collective diffusivities of colloid-polymer suspensions aimed at elucidating the
      relative contributions of hydrodynamics and thermodynamics as a phase transition
      or gelation boundary is approached. The experimental system is a hard sphere
      octadecyl silica suspension to which nonadsorbing polystyrene is added. Two
      different polymer molecular weights are chosen such that they give rise to a
      liquid-liquid or a gel transition as the colloid volume fraction or polymer
      concentration is increased. The short-time diffusivities are measured for each
      polymer molecular weight as a function of polymer concentration and colloid
      volume fraction. At a fixed polymer molecular weight and concentration, the
      colloid volume fraction is varied from dilute to concentrated and near the phase
      separation boundary. It is found for all measured colloid volume fractions that
      the diffusivities decrease linearly with increasing strength of the polymer
      mediated depletion attraction at a fixed polymer molecular weight. Comparisons
      are made with theoretical predictions in the dilute limit. When the effects of
      thermodynamics are normalized out by multiplying the measured diffusivities with
      the suspension structure factor, it is found that the hydrodynamic effects are
      essentially those of hard spheres independent of the range and strength of
      depletion attraction.

PMID- 19583188
TI  - Direct UV observation and kinetic studies of a alpha-alkoxy benzyloxy radical.
AB  - A alpha-alkoxy benzyloxy radical 3 was generated by laser flash photolysis of
      peroxyacetal 2, and its UV spectrum, decomposition pattern, reactivity with
      PPh(3), O(2), and i-PrOH, and quantum yield were explored. It was found that the
      radical 3 is very unstable and highly reactive and performs beta-C-H scission
      much faster than beta-C-O scission and H-abstraction.

PMID- 19583190
TI  - A simple method to produce trivalent colloidal particles.
AB  - Trivalent patchy colloidal particles are synthesized using a two-step mu-contact
      printing method. First, one pole of a particle is modified, then the other. With
      the center portion of the particle left intact, the final chemical makeup
      consists of three distinct patches of different chemical composition whose
      relative areas can be controlled. This method depends on preparing stamps with
      sufficient adhesion to lift off particles yet mild enough adhesion for their
      subsequent detachment. Furthermore, this method adjusts stamp stiffness, allowing
      the respective areas of the two printed poles to be controlled separately. To
      check the efficacy of the method, the shapes of the chemically modified poles
      were examined using scanning electron microscopy (SEM) after Au nanoparticle
      adsorption. Fluorescence imaging further confirmed the trivalent patchy particle
      geometry.

PMID- 19583189
TI  - Amphiphilicity in homopolymer surfaces reduces nonspecific protein adsorption.
AB  - Amphiphilic homopolymer films have been immobilized onto substrates to study the
      interactions of these polymers with proteins. X-ray photoelectron spectroscopy
      (XPS) was utilized to measure the amount of protein adsorption. Amphiphilic
      homopolymers have been shown to reduce protein adsorption, despite the high
      affinity of the hydrophobic or hydrophilic functional groups by themselves toward
      proteins. This protein-resistant property seems to arise from the unique
      molecular-scale alternation of incompatible functionalities. The combination of
      incompatible functionalities with a predefined alternating pattern within a
      monomer could provide a potential design for nonfouling materials.

PMID- 19583191
TI  - Solvation of carbon nanotubes in a room-temperature ionic liquid.

PMID- 19583192
TI  - Photochemical covalent attachment of alkene-derived monolayers onto hydroxyl
      terminated silica.
AB  - The functionalization of optically transparent substrates is of importance, for
      example, in the field of biosensing. In this article, a new method for
      modification of silica surfaces is presented that is based on a photochemical
      reaction of terminal alkenes with the surface. This yields highly hydrophobic
      surfaces, which are thermally stable up to at least 400 degrees C. The formed
      monolayer provides chemical passivation of the underlying surface, according to
      studies showing successful blocking of platinum atomic layer deposition (ALD).
      The reaction is photochemically initiated, requiring light with a wavelength
      below 275 nm. X-ray photoelectron spectroscopy and infrared spectroscopy studies
      show that the alkenes initially bind to the surface hydroxyl groups in
      Markovnikov fashion. At prolonged reaction times (>5 h), however, oligomerization
      occurs, resulting in layer growth normal to the surface. The photochemical nature
      of the reaction enables the use of photolithography as a tool to constructively
      pattern silica surfaces. Atomic force microscopy shows that the features of the
      photomask are well transferred. The newly developed method can complement
      existing patterning methods on silica that are based on soft lithography.

PMID- 19583193
TI  - Analog noise reduction in enzymatic logic gates.
AB  - In this work, we demonstrate both experimentally and theoretically that the
      analog noise generation by a single enzymatic logic gate can be dramatically
      reduced to yield gate operation with virtually no input noise amplification. We
      demonstrate that when a cosubstrate with a much smaller affinity than the primary
      substrate is used, a negligible increase in the noise output from the logic gate
      is obtained, as compared to the input noise level. Our general theoretical
      conclusions were confirmed by experimental realizations of the AND logic gate
      based on the enzyme horseradish peroxidase using hydrogen peroxide as the
      substrate, with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) or
      ferrocyanide as cosubstrates with vastly different rate constants.

PMID- 19583194
TI  - Adsorption and molecular rearrangement of amphoteric species at oil-water
      interfaces.
AB  - The formation of stable water-in-petroleum emulsions is a costly challenge when
      transporting, processing, and refining heavy crude oil and bitumen. The stability
      of these emulsions is attributed to interfacial films with well-documented
      viscoelastic properties that are known to vary with concentration, solvent
      quality, and asphaltene chemistry. In this study, we explore the impact of
      aqueous phase pH and salinity on the transient interfacial rheological properties
      of asphaltenic films. Using two chemically unique asphaltenes, interfacial shear
      rheology revealed an apparent salt-induced retardation of the interfacial
      consolidation processes that ultimately engender elasticity to the film. For
      Hondo asphaltenes at pH 7, a linear dependence of this retardation on the Debye
      parameter (kappa) suggested that shielding of electrostatic attraction was
      responsible. Further investigation with dynamic oscillating drop tensiometry at
      pH 3, 7, and 10 illustrated that intralayer repulsive and attractive
      electrostatic interactions can significantly influence the evolution of the
      interfacial structure. More specifically, the transient tension and dilatational
      modulus profiles indicated several interfacial processes were affected by the
      addition of salt, including (i) interfacial activity and the extent of
      adsorption, (ii) interfacial rearrangement and consolidation, and (iii)
      interfacial transport or displacement or both. Furthermore, the observed
      asphaltene interfacial behavior was consistent with those published for
      interfacial structure-forming amphoteric proteins, such as lysozyme and beta
      casein.

PMID- 19583195
TI  - Potential energy surfaces for vibrational structure calculations from a
      multiresolution adaptive density-guided approach: implementation and test
      calculations.
AB  - A multiresolution procedure to construct potential energy surfaces (PESs) for use
      in vibrational structure calculations is developed in the framework of the
      adaptive density-guided approach. The implementation of the method allows the
      construction of hybrid PESs with different mode-coupling terms calculated with a
      variety of combinations of electronic structure methods and basis sets.
      Furthermore, the procedure allows the construction of hybrid PESs that
      incorporate a variety of contributions and corrections to the electronic energy,
      such as infinite basis set extrapolation and core correlation effects. A full
      account of the procedure is given together with a rather large set of benchmark
      calculations on a set of 20 small molecules, from diatomics to tetratomics.

PMID- 19583196
TI  - Energetic differences at the subunit interfaces of normal human hemoglobins
      correlate with their developmental profile.
AB  - A previously unrecognized function of normal human hemoglobins occurring during
      protein assembly is described, i.e. self-regulation of subunit pairings and their
      durations arising from the variable strengths of their subunit interactions.
      Although many mutant human hemoglobins are known to have altered subunit
      interface strengths, those of the normal embryonic, fetal, and adult human
      hemoglobins have not been considered to differ significantly. However, in a
      comprehensive study of both types of subunit interfaces of seven of the eight
      normal oxy human hemoglobins, we found that the strengths, i.e., the free
      energies of the tetramer-dimer interfaces, contrary to previous reports, differ
      by 3 orders of magnitude and display an undulating profile similar to the
      transitions ("switches") of various globin subunit types over time. The dimer
      interface strengths are also variable and correlate linearly with their
      developmental profile. Embryonic hemoglobins are the weakest; fetal hemoglobin is
      of intermediate strength, and adult hemoglobins are the strongest. The pattern
      also correlates generally with their different O(2) affinities and responses to
      allosteric regulatory molecules. Acetylation of fetal hemoglobin weakens its
      unusually strong subunit interactions and occurs progressively as its level of
      expression diminishes and adult hemoglobin A formation begins; a causal
      relationship is suggested. The relative contributions of globin gene order and
      competition among subunits due to differences in their interface strengths were
      found to be complementary and establish a connection among genetics,
      thermodynamics, and development.

PMID- 19583197
TI  - High-accuracy extrapolated ab initio thermochemistry of the propargyl radical and
      the singlet C(3)H(2) carbenes.
AB  - Total atomization energies and enthalpies of formation (0 and 298.15 K) are
      evaluated using the high-accuracy extrapolated ab initio thermochemistry (HEAT)
      scheme for the two stable singlet C(3)H(2) carbenes [cyclopropenylidene (c
      C(3)H(2)) and propadienylidene (vinylidencarbene, l-C(3)H(2))], as well as for
      the 2-propynyl (propargyl, C(3)H(3)) radical. In the case of propargyl, the HEAT
      protocol predicts an enthalpy of formation of 354.9 +/- 1.0 kJ mol(-1) for 0 K;
      corresponding values of 498.1 +/- 1.0 and 555.6 +/- 1.0 kJ mol(-1) are estimated
      for c-C(3)H(2) and l-C(3)H(2). Additional consideration of temperature
      corrections leads to estimates of 352.2 +/- 1.0, 497.1 +/- 1.0, and 556.7 +/- 1.0
      kJ mol(-1) for the heats of formation at 298.15 K of the propargyl radical, c
      C(3)H(2), and l-C(3)H(2), respectively. Potential strategies for simplifying the
      HEAT protocol are also investigated and shown to have negligible impact on
      accuracy.

PMID- 19583198
TI  - A first principle analysis of the structure of oligoanilines doped with
      alkylsulfonic acids.
AB  - The interaction of polyaniline with alkylsulfonate dopants have been investigated
      at the atomic level using quantum mechanical methods. Calculations have been
      performed on complexes formed by dopant molecules with an alkyl group ranging
      from methyl to nonyl and model oligoanilines of different sizes. The
      stabilization provided by the formation of the alkylsulfonate...oligoaniline
      complexes (70-90 kcal/mol) is significantly higher than that found for
      conventional hydrogen bonds (5-12 kcal/mol) but lower than that obtained for
      methylsulfate...alkylammonium and methylsulfate...Na(+) systems (120-135
      kcal/mol). On the other hand, the influence of size of the alkyl group contained
      in the dopant on the interaction is practically negligible, whereas, in
      opposition, the number of aniline units used to represent polyaniline
      significantly affects the energetics of the interaction. Specifically, the
      interaction energy of an alkyl-dopant molecule and an infinite polyaniline chain
      has been predicted to be around -65 kcal/mol. The overall results allow the
      conclusion that the interaction between alkylsulfonate dopants and polyaniline is
      a very local phenomenon.

PMID- 19583199
TI  - Diastereo- and enantioselective Aza-MBH-type reaction of nitroalkenes to N
      tosylimines catalyzed by bifunctional organocatalysts.
AB  - The first example of diastereo- and enantioselective aza-MBH-type reaction was
      accomplished by the asymmetric synthesis of beta-nitro-gamma-enamines via a
      (1R,2R)-diaminocyclohexane thiourea derivative mediated tandem Michael addition
      and aza-Henry reaction in good yields (up to 95%) and high enantioselectivities
      (up to 91% ee) and diastereoselectivities (up to 1:99 dr).

PMID- 19583200
TI  - Palladium-catalyzed decarboxylative arylation of C-H bonds by aryl acylperoxides.
AB  - A Pd(OAc)(2)-catalyzed protocol for decarboxylative arylation of aromatic C-H
      bond was developed using aryl acylperoxides as inexpensive aryl sources.
      Substrates containing pyridyl, oxime, and oxazoline groups undergo effectively
      ortho-selective C-H arylation with excellent functional group tolerance. This
      arylation should begin by directing-group-assisted cyclopalladation, followed by
      the reaction of the palladacycle with aryl radicals generated in situ by thermal
      decomposition of the peroxides.

PMID- 19583201
TI  - Nondestructive, colorimetric monitoring of amines and thiols on a solid support.
AB  - A new, nondestructive, highly sensitive method for colorimetric monitoring of
      primary amines, secondary amines, and thiols on a solid support was developed.
      The resin used in this method is simply regenerated for the repetition of the
      reaction or an ensuing reaction. By using this new method, several peptides
      containing secondary amide linkages and C-terminal hydrazide groups were prepared
      in high purities and yields.

PMID- 19583202
TI  - Edaxadiene: a new bioactive diterpene from Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis remains a widespread and devastating human pathogen.
      Presented here is the characterization of an atypical class I diterpene cyclase
      from M. tuberculosis that catalyzes an unusual cyclization reaction in converting
      the known M. tuberculosis metabolite halimadienyl diphosphate to a further
      cyclized novel diterpene, which we have termed edaxadiene, as it directly
      inhibits maturation of the phagosomal compartment in which the bacterium is taken
      up during infection.

PMID- 19583203
TI  - Energy level alignment in CdS quantum dot sensitized solar cells using molecular
      dipoles.
AB  - The energy levels of CdS quantum dots (QDs) can be shifted in a systematic
      fashion with respect to the TiO(2) bands using molecular dipoles. Dipole moments
      pointing toward the QD surface shift the energy levels toward the vacuum level
      (a), thus enabling electron injection from excited QD states into the TiO(2)
      conduction band at lower photon energies compared to QDs with adsorbed molecular
      dipoles which are pointing away from the QD surface (b). In CdS QD sensitized
      solar cells this leads to a dipole dependent shift of the photovoltage onset and
      the photocurrent.

PMID- 19583204
TI  - Efficient approach to fluvirucins B2-B5, Sch 38518, and Sch 39185. First
      synthesis of their aglycon, via CM and RCM reactions.
AB  - A route to fluvirucinins B(2-5) (the common aglycon of fluvirucins B(2)-B(5), Sch
      38518, and Sch 39185) is reported for the first time. A ring-closing metathesis
      (RCM) generated the C6-C7 double bond, which by catalytic hydrogenation (in
      toluene) gave the desired epimer with a 9:1 diastereoselection. Azide 8a and
      carboxylic acid 5 came from ethyl-branched fragments C9-C13 (CHO at C9) and C1-C5
      via an asymmetric allylation of the former and a cross metathesis (CM) followed
      by a ketone methylenation (with 20 mol % of DMF as a sacrificial additive) of the
      latter.

PMID- 19583205
TI  - Cobalt-catalyzed 1,4-hydrovinylation of styrenes and 1-aryl-1,3-butadienes.
AB  - The application of aryl-substituted starting materials such as styrene and 1-aryl
      substituted 1,3-butadiene derivatives in the cobalt-catalyzed 1,4-hydrovinylation
      reaction has been investigated. The use of unsymmetrical alpha,omega-dienes in
      the hydrovinylation with 1-aryl-1,3-butadiene led chemoselectively to the 1:1 or
      the 1:2 adducts depending on the stoichiometry of the starting materials.

PMID- 19583206
TI  - Birch reductions at room temperature with alkali metals in silica gel (Na2K
      SG(I)).
AB  - Alkali metals in silica gel (the Na(2)K-SG(I) reagent) cleanly effect Birch
      reductions of substrates with at least two or more aromatic rings. The reaction
      conditions are alcohol-free, ammonia-free, and achieve excellent yields and high
      selectivities at room temperature.

PMID- 19583207
TI  - Crystallographic snapshots of cyanide- and water-bound C-clusters from
      bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
AB  - Nickel-containing carbon monoxide dehydrogenases (CODHs) reversibly catalyze the
      oxidation of carbon monoxide to carbon dioxide and are of vital importance in the
      global carbon cycle. The unusual catalytic CODH C-cluster has been
      crystallographically characterized as either a NiFe(4)S(4) or a NiFe(4)S(5) metal
      center, the latter containing a fifth, additional sulfide that bridges Ni and a
      unique Fe site. To determine whether this bridging sulfide is catalytically
      relevant and to further explore the mechanism of the C-cluster, we obtained
      crystal structures of the 310 kDa bifunctional CODH/acetyl-CoA synthase complex
      from Moorella thermoacetica bound both with a substrate H(2)O/OH(-) molecule and
      with a cyanide inhibitor. X-ray diffraction data were collected from native
      crystals and from identical crystals soaked in a solution containing potassium
      cyanide. In both structures, the substrate H(2)O/OH(-) molecule exhibits binding
      to the unique Fe site of the C-cluster. We also observe cyanide binding in a bent
      conformation to Ni of the C-cluster, adjacent the substrate H(2)O/OH(-) molecule.
      Importantly, the bridging sulfide is not present in either structure. As these
      forms of the C-cluster represent the coordination environment immediately before
      the reaction takes place, our findings do not support a fifth, bridging sulfide
      playing a catalytic role in the enzyme mechanism. The crystal structures
      presented here, along with recent structures of CODHs from other organisms, have
      led us toward a unified mechanism for CO oxidation by the C-cluster, the
      catalytic center of an environmentally important enzyme.

PMID- 19583208
TI  - Structural basis of cyanide inhibition of Ni, Fe-containing carbon monoxide
      dehydrogenase.
AB  - Carbon monoxide dehydrogenases (CODHs) catalyze the reversible oxidation of
      carbon monoxide with water to carbon dioxide, two protons, and two electrons. The
      CODHs of anaerobic microorganisms harbor a complex Ni/Fe/S-containing metal
      center called a C-cluster in their active site, which activates the substrates
      water and carbon monoxide, stabilizes an intermediary metal-carboxylate, and
      transiently stores the two electrons generated in the reaction. Several small
      molecules have been reported to inhibit carbon monoxide oxidation by CODHs, among
      which the cyanide anion acts as a slow binding inhibitor. Cyanide is
      isoelectronic to the substrate carbon monoxide, and its binding to the C-cluster
      has been reported to involve nickel, nickel and iron, or only iron. We report the
      crystal structure of CODH-II from Carboxydothermus hydrogenoformans in complex
      with cyanide at 1.36 A resolution. The structure reveals that cyanide binds to
      the C-cluster at an open coordination site completing the square-planar
      coordination geometry of the nickel ion. While active CODH has a water/hydroxo
      ligand bound to an iron ion near nickel, in the cyanide complex the water/hydroxo
      ligand is lost and iron occupies a position more close to the nickel ion. Based
      on the structure, we suggest that the competitive inhibitory character of cyanide
      originates from it obstruction of carbon monoxide binding to the nickel ion while
      the slow binding inhibition is due to a conformational change of the protein
      during which the water/hydroxo-ligand bound to iron is lost.

PMID- 19583209
TI  - Positively charged base surrogate for highly stable "base pairing" through
      electrostatic and stacking interactions.
AB  - "Base pairs" of cationic dyes (p-methylstilbazole) were incorporated into
      oligodeoxyribonucleotides (ODNs). This "base pair" greatly stabilized the duplex
      through electrostatic and stacking interactions. The melting temperature of
      modified ODN was higher than those of neutral dyes and native base pairs. Further
      stabilization of the duplex was observed when the number of cationic dyes
      increased.

PMID- 19583210
TI  - Revisiting the IspH catalytic system in the deoxyxylulose phosphate pathway:
      achieving high activity.
AB  - From two C(5) isoprene building blocks, isopentenyl diphosphate (IPP) and its
      isomer dimethylallyl diphosphate (DMAPP), the more than 30 000 members of the
      isoprenoid family are constructed in nature using two biosynthetic pathways, the
      mevalonate (MVA) pathway and the deoxyxylulose phosphate (DXP) pathway. IspH of
      the DXP pathway is a protein containing an iron-sulfur cluster and catalyzes a
      reductive dehydration reaction of the DXP pathway. In the literature, a wide
      range of Escherichia coli IspH activities have been reported (2.0 nmol min(-1)
      mg(-1) to 3.4 micromol min(-1) mg(-1)). For such a broad range of activities,
      reaction assays were carried out under many different conditions, preventing
      direct comparison of the activities and determination of the key factor
      responsible for such a dramatic difference in IspH activities. In this work, we
      systematically examined the role of redox mediators in IspH catalysis using E.
      coli IspH as the enzyme and dithionite as the ultimate electron source. Our
      studies not only suggest the importance of the iron-sulfur cluster but also
      improve the E. coli IspH activity by nearly 97-fold relative to that from the E.
      coli NADPH-flavodoxin reductase-flavodoxin system.

PMID- 19583211
TI  - Oligomer assembly of the C-terminal DISC1 domain (640-854) is controlled by self
      association motifs and disease-associated polymorphism S704C.
AB  - Genetic studies have established a role of disrupted-in-schizophrenia-1 (DISC1)
      in chronic mental diseases (CMD). Limited experimental data are available on the
      domain structure of the DISC1 protein although multiple interaction partners are
      known including a self-association domain within the middle part of DISC1
      (residues 403-504). The DISC1 C-terminal domain is deleted in the original
      Scottish pedigree where DISC1 harbors two coiled-coil domains and disease
      associated polymorphisms at 607 and 704, as well as the important nuclear
      distribution element-like 1 (NDEL1) binding site at residues 802-839. Here, we
      performed mutagenesis studies of the C-terminal domain of the DISC1 protein
      (residues 640-854) and analyzed the expressed constructs by biochemical and
      biophysical methods. We identified novel DISC1 self-association motifs and the
      necessity of their concerted action for orderly assembly: the region 765-854
      comprising a coiled-coil domain is a dimerization domain and the region 668-747
      an oligomerization domain; dimerization was found to be a prerequisite for
      orderly assembly of oligomers. Consistent with this, disease-associated
      polymorphism C704 displayed a slightly higher oligomerization propensity. The
      heterogeneity of DISC1 multimers in vitro was confirmed with a monoclonal
      antibody binding exclusively to HMW multimers. We also identified C-terminal
      DISC1 fragments in human brains, suggesting that C-terminal fragments could carry
      out DISC1-dependent functions. When the DISC1 C-terminal domain was transiently
      expressed in cells, it assembled into a range of soluble and insoluble multimers
      with distinct fractions selectively binding NDEL1, indicating functionality. Our
      results suggest that assembly of the C-terminal domain is controlled by distinct
      domains including the disease-associated polymorphism 704 and is functional in
      vivo.

PMID- 19583212
TI  - Structural, UV-visible, and electrochemical studies on 2,3-dicyano-5,6-di-2
      pyridylpyrazine, [(CN)2Py2Pyz], related species and its complexes
      [(CN)2Py2PyzMCl2] (M = Pt(II), Pd(II)).
AB  - 2,3-Dicyano-5,6-di-2-pyridylpyrazine, [(CN)(2)Py(2)Pyz], which
      autocyclotetramerizes to give the macrocycle tetrakis[5,6-di(2-pyridyl)-2,3
      pyrazino]porphyrazine, [Py(8)TPyzPzH(2)], bearing externally four
      dipyridinopyrazine fragments, reacts with bis(benzonitrile)dichloroplatinum(II),
      [(C(6)H(5)CN)(2)PtCl(2)], in CH(3)CN, affording the monometalated species
      [(CN)(2)Py(2)PyzPtCl(2)]. Single-crystal X-ray work on this compound shows that
      Pt(II) is bound to [(CN)(2)Py(2)Pyz] through the two pyridine N atoms ("py-py"
      coordination) in a way similar to that found for its monopalladium analogue,
      [(CN)(2)Py(2)PyzPdCl(2)]. Cyclic voltammetry of [(CN)(2)Py(2)PyzPtCl(2)] and
      [(CN)(2)Py(2)PyzPdCl(2)] in nonaqueous media (pyridine, DMSO, and DMF) indicates
      that the electron-withdrawing effect of the coordinated PtCl(2) and PdCl(2) units
      results in an initial one-electron reduction (E(1/2) = -0.60 and -0.54 V vs SCE
      in DMSO, respectively), which is easier by 0.25-0.30 V than the unmetalated
      [(CN)(2)Py(2)Pyz] (first reduction: E(1/2) = -0.87 V vs SCE). These
      electrochemical data are analyzed along with new results for a selected number of
      related pyrazine and 2,3-dicyanopyrazine molecules as well as earlier reported
      data on the mono- and bis-N-methylated derivatives [(CN)(2)Py(2-Mepy)Pyz](+) and
      [(CN)(2)(2-Mepy)(2)Pyz](2+), with these latter species being formed by reaction
      of the precursor [(CN)(2)Py(2)Pyz] with methyl iodide or p-toluensulfonate. The
      data in this study are also compared to electrochemical data previously reported
      for a triad of palladium(II) porphyrazine macrocycles obtained from the precursor
      [(CN)(2)Py(2)Pyz], i.e., [Py(8)TPyzPzPd], the corresponding pentanuclear complex
      [(PdCl(2))(4)Py(8)TPyzPzPd] (presenting "py-py" coordination at the
      dipyridinopyrazine fragments), and the octacation [(2-Mepy)(8)TPyzPzPd](8+) (N
      methylated at the pyridine rings). Thin-layer UV-visible spectra of singly
      reduced [(CN)(2)Py(2)Pyz](-) and its metalated analogues,
      [(CN)(2)Py(2)PyzPtCl(2)](-) and [(CN)(2)Py(2)PyzPdCl(2)](-), were measured in
      pyridine, DMF, and DMSO and show pi-pi* transitions, as well as unusually intense
      absorptions in the near-IR region (500-900 nm) of the spectrum.

PMID- 19583213
TI  - A straightforward protocol for one-pot allylic aminations/Stille couplings.
AB  - Stannylated allylic carbonates are suitable substrates for Pd-catalyzed allylic
      aminations. In DMF and with [Pd(allyl)Cl](2) as catalyst, the stannylated allyl
      amines formed can be directly coupled with electrophiles according to the Stille
      protocol, giving rise to highly functionalized building blocks in excellent
      yields.

PMID- 19583214
TI  - Medium-sized carbocycles by samarium diiodide-induced carbonyl-alkene
      cyclizations.
AB  - Intramolecular samarium diiodide-induced carbonyl-alkene or carbonyl-alkyne
      coupling reactions afforded without high dilution conditions 9- and 10-membered
      benzannulated carbocycles of type II and III in surprisingly good yields and
      stereoselectivities. A novel samarium diiodide-mediated cascade process leading
      to tricyclic compounds of type IV was also observed. Bisbenzannulated 10- and 11
      membered carbocycles were prepared in very good yields.

PMID- 19583215
TI  - Palladium-catalyzed cyclocarbonylation-decarboxylation of diethyl(2
      iodoaryl)malonates with vinyl ketones affording functionalized enolic 2-acyl-3,4
      dihydronaphthalenones.
AB  - A wide variety of enolic tautomers of functionalized 2-acyl-3,4-dihydronaphthalen
      1(2H)-ones were obtained in moderate to excellent yields by the palladium
      catalyzed cyclocarbonylation-decarboxylation of diethyl(2-iodoaryl)malonates with
      vinyl ketones and carbon monoxide. The reaction may proceed via the formation of
      a keto-diester, followed by oxidative addition, CO insertion, intramolecular
      cyclization, and decarboxylation to give the enolic substituted 2
      acyldihydronaphthalenones.

PMID- 19583217
TI  - Online integration of multiple sample pretreatment steps involving denaturation,
      reduction, and digestion with microflow reversed-phase liquid chromatography
      electrospray ionization tandem mass spectrometry for high-throughput proteome
      profiling.
AB  - A facile integrated platform for proteome profiling was established, in which
      native proteins were online denatured and reduced within a heater, digested with
      an immobilized trypsin microreactor, and analyzed by microflow reversed-phase
      liquid chromatography with electrospray ionization tandem mass spectrometry
      (microRPLC-ESI-MS/MS). In comparison to the traditional off-line urea
      denaturation protocol, even more unique peptides were obtained by online heating
      in triplicate (14 +/- 2 vs 11 +/- 2 for myoglobin and 16 vs 12 +/- 1 for BSA)
      within a significantly shortened pretreatment time of approximately 3.5 min
      (including 1 min of thermal denaturation and reduction and approximately 2.5 min
      of microreactor digestion). Moreover, proteins with concentrations ranging from
      50 ng/mL (approximately 6 fmol) to 1 mg/mL (approximately 120 pmol) were
      positively identified by the online system. Such a platform was further
      successfully applied for analyzing the soluble fraction of mouse liver extract.
      Of all the 367 proteins identified from samples pretreated by the urea protocol
      and online heating, approximately 40% were overlapped, showing the partial
      complementation of both approaches. All these results demonstrate that the online
      integrated platform is of great promise for high-throughput proteome profiling
      and improved identification capacity for low-abundance proteins with a minute
      sample amount.

PMID- 19583218
TI  - Electrochemical biosensing using amplification-by-polymerization.
AB  - A novel signal amplification strategy for electrochemical detection of DNA and
      proteins based on the amplification-by-polymerization concept is described.
      Specifically, a controlled radical polymerization reaction is triggered after the
      capture of target molecules on the electrode surface. Growth of long chain
      polymeric materials provides numerous sites for subsequent aminoferrocene
      coupling, which in turn significantly enhances electrochemical signal output.
      Activators generated electron transfer for atom transfer radical polymerization
      (AGET ATRP) is used in this study for its high efficiency in polymer grafting and
      better tolerance toward oxygen in air. 2-Hydroxyethyl methacrylate (HEMA) and
      glycidyl methacrylate (GMA) are examined to provide excess hydroxyl or epoxy
      groups for aminoferrocene coupling. A limit of detection of 15 pM and 0.07 ng/mL
      is demonstrated for DNA and ovalbumin, respectively. More than 7-fold signal
      enhancement in ovalbumin detection has been achieved comparing to the unamplified
      method. In addition, a more than 5 orders of magnitude of dynamic range is
      achieved with a linear correlation coefficient (R(2)) of 0.997 for DNA, and a
      more than 3 orders of magnitude with R(2) of 0.999 for ovalbumin. Together, the
      results show that the coupling of amplification-by-polymerization concept with
      electrochemical detection offers great promises in providing a sensitive and cost
      effective solution for biosensing applications.

PMID- 19583219
TI  - Identification of Escherichia coli HemG as a novel, menadione-dependent
      flavodoxin with protoporphyrinogen oxidase activity.
AB  - Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the six-electron oxidation
      of protoporphyrinogen IX to the fully conjugated protoporphyrin IX. Eukaryotes
      and Gram-positive bacteria possess an oxygen-dependent, FAD-containing enzyme for
      this step, while the majority of Gram-negative bacteria lack this oxygen
      dependent PPO. In Escherichia coli, PPO activity is known to be linked to
      respiration and the quinone pool. In E. coli SASX38, the knockout of hemG causes
      a loss of measurable PPO activity. HemG is a small soluble protein typical of
      long chain flavodoxins. Herein, purified recombinant HemG was shown to be capable
      of a menadione-dependent conversion of protoporphyrinogen IX to protoporphyrin
      IX. Electrochemical analysis of HemG revealed similarities to other flavodoxins.
      Interestingly, HemG, a member of a class of the long chain flavodoxin family that
      is unique to the gamma-proteobacteria, possesses a 22-residue sequence that, when
      transferred into E. coli flavodoxin A, produces a chimera that will complement an
      E. coli hemG mutant, indicating that this region confers PPO activity to the
      flavodoxin. These findings reveal a previously unidentified class of PPO enzymes
      that do not utilize oxygen as an electron acceptor, thereby allowing gamma
      proteobacteria to synthesize heme in both aerobic and anaerobic environments.

PMID- 19583220
TI  - Solution-phase parallel synthesis of Hsp90 inhibitors.
AB  - As part of an oncology chemistry program directed toward discovery of orally
      bioavailable inhibitors of the 90 kDa heat shock protein (Hsp90), several
      solution-phase libraries were designed and prepared. A 2 x 89 library of racemic
      resorcinol amides was prepared affording 131 purified compounds. After evaluation
      in a binding assay, followed by an AKT-Luminex cellular assay, three potent
      analogs had functional activity between 0.1 and 0.3 microM. Resolution by
      preparative chiral SFC chromatography led to (+)-15, (+)-16, and (+)-17 having
      functional IC(50) = 27, 43, and 190 nM, respectively. (+)-15 exhibited high
      clearance in human hepatocytes driven primarily by glucuronidation as confirmed
      by metabolite identification. A second 8 x 14 exploratory library was designed to
      investigate heterocyclic replacements of the resorcinol ring. The second library
      highlights the use of the (-)-sparteine-mediated enantioselective Pd-catalyzed
      alpha-arylation of N-Boc-pyrrolidine to prepare chiral 2-arylpyrrolidines in
      parallel.

PMID- 19583221
TI  - Highly ordered conjugated polymer nanoarchitectures with three-dimensional
      structural control.
AB  - Conductive polymers are a class of materials with vast potential for tomorrow's
      ultra-large-scale technologies as they combine structural and functional
      diversity with flexible synthesis and processing approaches. A missing component,
      with their subtle chemical structure, is reliable building at nanoscale. Here we
      report on the patterning of polyaniline, a prototypical conjugated polymer, with
      an unprecedented areal patterning order and density exceeding 0.25
      teradot/inch(2). With template-confined growth, through platinum-surface
      catalyzed polymerization of aniline, highly ordered arrays of distinct
      polyaniline nanowires are produced with a typical diameter <or=15 nm and aspect
      ratio higher than 20. Up-scaling is straightforward. Complex three-dimensional
      structural control is achieved through a direct pattern transfer via resist- and
      dose-modulated electron beam lithography. The morphology-modulated nanowires self
      assemble in key-lock type architectures induced by the structure asymmetry and
      nonuniformity of the capillary forces associated with the re-entrant features.

PMID- 19583222
TI  - Shannon entropy-based fingerprint similarity search strategy.
AB  - For fingerprint searching using multiple active reference compounds, an
      information entropy-based similarity method is introduced as an alternative to
      conventional similarity coefficients and search strategies. The approach involves
      the determination of the fingerprint bit pattern entropy of a compound reference
      set and recalculation of the entropy following the addition of individual test
      compounds. If a database compound shares similar bit patterns with reference set
      molecules, adding this compound to the reference set only produces a small change
      in system entropy. By contrast, inclusion of a compound having a dissimilar
      fingerprint leads to a notable increase in entropy. Thus, database compounds can
      be screened for candidate molecules that do not cause significant changes in
      reference set fingerprint entropy. Compared to nearest neighbor methods, this
      approach has the computational advantage that it extracts reference set
      information only once prior to similarity searching. Test calculations on
      different compound data sets, fingerprints, and screening databases reveal that
      the ability of our entropy-based method to detect active compounds is often
      superior to data fusion techniques and Tanimoto similarity calculations.

PMID- 19583223
TI  - Preparation and characterization of biocompatible microcapsules of sodium
      cellulose sulfate/chitosan by means of layer-by-layer self-assembly.
AB  - A novel microcapsule system composed of sodium cellulose sulfate (NaCS) and
      chitosan was prepared by layer-by-layer (LbL) self-assembly technique. As a
      potential drug delivery system, it had several advantages in biocompatibility and
      biodegradation due to its use of natural polysaccharides. Some parameters in the
      preparation of the microcapsule, such as layers in the LbL process (up to 20
      layers), chitosan viscosities (50, 100, and 200 mPas), outmost layer materials
      (NaCS or chitosan), and NaCl concentrations (0 M, 0.5 M, 1 M), were investigated
      to better understand their effects on the LbL process. A novel method for
      removing the core templates PLA and CaCO3 from the formed core-shell structure
      was proposed by addition of N-methyl pyrrolidone or EDTA-Na. This preparation
      process was well observed by a microscope-camera system. The hollow microcapsules
      were tested by scanning electron microscopy (SEM), confocal laser scanning
      microscopy (CLSM) and scanning probe microscopy (SPM) to characterize their size,
      morphology, and surface. The results showed that the shell thickness of
      microcapsules was about 6 nm, and the average thickness of one layer of
      NaCS/chitosan polyelectrolyte complex was 1.5 nm. The molecular weight cutoff in
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed about
      70 kDa by using of diffusion test with the cell lysate of Escherichia coli.

PMID- 19583225
TI  - Interfacial interactions in aprotic ionic liquid based protonic membrane and its
      correlation with high temperature conductivity and thermal properties.
AB  - Novel supported liquid membranes (SLMs) have been developed by impregnating
      Nafion and Hyflon membranes with ionic liquid 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (BMI-BTSI). These supported liquid membranes
      were characterized in terms of their ionic liquid uptake behavior, leaching of
      ionic liquid by water, thermal stability, mechanical properties, glass transition
      temperature, ion exchange capacity, and proton conductivity. In general, modified
      membranes are more flexible than unmodified samples due to the plasticization
      effects of the ionic liquid. However, these supported liquid membranes exhibit a
      significant increase in their operational stability and proton conductivity over
      unmodified membranes. We also demonstrate that proton conductivity of these
      supported liquid membranes allows conduction of protons in anhydrous conditions
      with conductivity increasing with temperature. Conductivity of up to 3.58 mS cm(
      1) has been achieved at 160 degrees C in dry conditions, making these materials
      promising for various electrochemical applications.

PMID- 19583224
TI  - Air bubble bursting effect of lotus leaf.
AB  - In this paper, a phenomenon of air bubbles quickly bursting within several
      milliseconds on a "self-cleaning" lotus leaf was described. This observation
      prompted the synthesis of artificial surfaces similar to that of the lotus leaf.
      The artificial leaf surfaces, prepared by photolithography and wet etching,
      showed a similar air bubble bursting effect. Smooth and rough silicon surfaces
      with an ordered nanostructure or patterned microstructure were utilized to study
      the contribution of the micro/nano hierarchical structures to this phenomenon of
      air bubble bursting. Air bubbles were found to burst on some superhydrophobic
      surfaces with microstructure (within 220 ms). However, air bubbles burst much
      more rapidly (within 13 ms) on similar surfaces with micro/nanostructure. The
      height, width, and spacing of hierarchical structures could also affect air
      bubble bursting, and the effect of the height was more obvious. When the height
      of hierarchical structures was around the height found in natural lotus papillae,
      the width and spacing were significant for air bubble bursting. An original model
      was proposed to further evaluate the reason why the micro/nano hierarchical rough
      structures had an excellent air bubble bursting effect, and the validity of the
      model was theoretically demonstrated.

PMID- 19583226
TI  - Influence of surface oxides on the colloidal stability of multi-walled carbon
      nanotubes: a structure-property relationship.
AB  - As with all nanomaterials, a large fraction of the atoms in carbon nanotubes
      (CNTs) reside at or near the surface. Consequently, surface chemistry will play a
      crucial role in determining the fate and transport of CNTs in aquatic
      environments. Frequently, oxygen-containing functional groups (surface oxides)
      are deliberately grafted into the CNT surface to promote colloidal stability. To
      study the influence that both the oxygen concentration and the oxygen functional
      group distribution have on the colloidal stability of multiwalled carbon
      nanotubes (MWCNTs), a suite of oxidized MWCNTs (O-MWCNTs) were created using
      different oxidizing agents and reaction conditions. Stable colloidal suspensions
      were prepared by low-power sonication of O-MWCNT powders in Milli-Q water.
      Results from TEM, AFM, DLS, and XPS measurements revealed that, irrespective of
      the surface chemistry, the colloidal suspensions were composed of individual
      nanotubes with comparable length distributions. The critical coagulation
      concentrations (CCC) of O-MWCNTs that exhibited different surface chemistries
      were measured with time-resolved dynamic light scattering (TR-DLS) using NaCl as
      the electrolyte. Over a range of environmentally relevant pH values, linear
      correlations were found to exist between the CCC, total oxygen concentration, and
      surface charge of O-MWCNTs. In contrast to surface charge, electrophoretic
      mobility did not prove to be a useful metric of colloidal stability. Information
      obtained from chemical derivatization studies, carried out in conjunction with
      XPS, revealed that the distribution of oxygen-containing functional groups also
      influences the colloidal stability of O-MWCNTs, with carboxylic acid groups
      playing the most important role. This study highlights the fact that quantitative
      relationships can be developed to rationalize the influence of surface chemistry
      on the behavior of nanomaterials in aquatic environments.

PMID- 19583227
TI  - Collective effects of multiple chiral selectors on enantioselective adsorption.
AB  - Molecular simulations were performed to predict the adsorption of racemic
      mixtures of (R,S)-1,3-dimethylallene (DMA) in three homochiral metal-organic
      frameworks (HMOFs). All three HMOFs include the same chiral linker, (R)-6,6'
      dichloro-2,2'-dihydroxy-1,1'-binaphthyl-4,4'-bipyridine (L), but have different
      topologies. While a single linker L shows very little enantioselectivity between
      the DMA enantiomers, the three HMOFs with closely packed linkers L have
      enantiomeric excesses of 6%, 28%, and 45%, showing that closely situated chiral
      selectors function synergistically to enhance the enantioselectivity. Both the
      confinement created by the linkers and the number of chiral linkers that form the
      confinement are important in enhancing the enantioselectivity. In addition, the
      simulations show that the enantioselectivity of the three HMOFs may be further
      enhanced by modifying the composition of the linker L.

PMID- 19583228
TI  - Structure and growth of vapor-deposited n-dotriacontane films studied by X-ray
      reflectivity.
AB  - We have used synchrotron X-ray reflectivity measurements to investigate the
      structure of n-dotriacontane (n-C(32)H(66) or C32) films deposited from the vapor
      phase onto a SiO(2)-coated Si(100) surface. Our primary motivation was to
      determine whether the structure and growth mode of these films differ from those
      deposited from solution on the same substrate. The vapor-deposited films had a
      thickness of approximately 50 A thick as monitored in situ by high-resolution
      ellipsometry and were stable in air. Similar to the case of solution-deposited
      C32 films, we find that film growth in vacuum begins with a nearly complete
      bilayer adjacent to the SiO(2) surface formed by C32 molecules aligned with their
      long axis parallel to the interface followed by one or more partial layers of
      perpendicular molecules. These molecular layers coexist with bulk particles at
      higher coverages. Furthermore, after thermally cycling our vapor-deposited
      samples at atmospheric pressure above the bulk C32 melting point, we find the
      structure of our films as a function of temperature to be consistent with a phase
      diagram inferred previously for similarly treated solution-deposited films. Our
      results resolve some of the discrepancies that Basu and Satija (Basu, S.; Satija,
      S. K. Langmuir 2007, 23, 8331) found between the structure of vapor-deposited and
      solution-deposited films of intermediate-length alkanes at room temperature.

PMID- 19583230
TI  - Capping and passivation of aluminum nanoparticles using alkyl-substituted
      epoxides.
AB  - We report here on the synthesis and passivation of small (20-30 nm) aluminum
      nanoparticles using alkyl-substituted epoxides as capping agents. FTIR and 13C
      NMR spectroscopy indicate that the epoxides polymerize to form a polyether cap on
      the surfaces of the aluminum nanoparticles. Nanoparticles capped with epoxyhexane
      and epoxydodecane are stable in air, but particles capped with epoxyisobutane are
      pyrophoric. TEM images show spherical Al particles. Powder X-ray diffraction
      shows the presence of crystalline Al. Titrimetric analysis of the core-shell
      nanostructures in air reveals that 96% of the total aluminum present is active
      (unoxidized) aluminum.

PMID- 19583229
TI  - Nanostructure of a poly(acrylic acid) brush and its transition in the amphiphilic
      diblock copolymer monolayer on the water surface.
AB  - The nanostructure and its transition of in a poly(acrylic acid) (PAA) brush in
      the water surface monolayers of poly(hydrogenated isoprene)-b-poly(acrylic acid)
      with different block lengths and block ratios were investigated by X-ray
      reflectivity as a function of surface pressure (brush density) and salt
      concentration in the subphase. The PAA brush showed the same behavior after salt
      addition as did the poly(methacrylic acid) (PMAA) brush, which was investigated
      previously. The brush chains expanded and then shrunk after passing the maximum
      with increasing added salt concentration. This behavior could be explained by the
      change in electric charges on the PAA brush chains as was observed on the PMAA
      brush. The PAA brush chains showed a critical brush density, where there was a
      transition between the carpet layer only and carpet + brush layer structures, as
      did the PMAA and poly(styrene sulfonic acid) (PSS) brushes. The critical brush
      density was about 0.4 chains nm(-2), which was higher than that of the PSS brush,
      a strong acid brush, and was close to that of the PMAA brush, a weak acid brush.
      However, the critical brush density of the PAA brush was independent of the
      hydrophilic chain length whereas that of the PMAA brush decreased with increasing
      PMAA chain length. In addition, the PAA brush had a thicker carpet layer than the
      PSS and PMAA brushes. Hence, the mechanism of PAA brush formation was predicted
      to be different from that of not only the PSS brush (strong acid brush) but also
      the PMAA brush.

PMID- 19583231
TI  - Divergent synthesis of the co-isolated mycotoxins longianone, isopatulin, and (Z)
      ascladiol via furan oxidation.
AB  - Longianone and the biosynthetically related mycotoxins isopatulin and (Z)
      ascladiol were prepared following a divergent route from a readily available
      furan diol. The route toward longianone features an unprecedented TBAF-promoted
      intramolecular oxa-Michael reaction to a conjugated keto enoate, and the
      oxidation of dihydrolongianone to longianone with stabilized IBX. The route to
      isopatulin features a chemoenzymatic synthesis of (Z)-ascladiol, and the
      regioselective oxidation of (Z)-ascladiol to isopatulin with MnO(2).

PMID- 19583232
TI  - Probing the interaction of magnetic iron oxide nanoparticles with bovine serum
      albumin by spectroscopic techniques.
AB  - The interaction of magnetic iron oxide nanoparticles (MNPs) with bovine serum
      albumin (BSA) was investigated by fluorescence (FL), ultraviolet visible (UV-vis)
      absorption, Raman, and circular dichroism (CD) spectroscopy. Results indicated
      that MNPs quench BSA FL mainly by a static quenching mechanism. The FL quenching
      constants KSV were obtained as 2.44x10(8), 2.41x10(8), and 2.40x10(8) L.mol(-1)
      at 291, 298, and 313 K, respectively. The thermodynamic parameters of enthalpy
      change DeltaH(theta), entropy change DeltaS(theta), and free energy change
      DeltaGtheta were -0.90 kJ.mol(-1), 157.38 J.mol(-1).K(-1), and -47.80 kJ.mol(-1)
      (298 K), respectively. The association constant (KA) and the number of binding
      sites (n) were 7.64x10(7) L.mol(-1) and 46.55 at higher concentration of MNPs,
      and 1.35x10(6) L.mol(-1) and 284.74 at lower concentration of MNPs. The analysis
      results suggested that the interaction was spontaneous and the electrostatic
      interactions played key roles in the reaction process. In addition, the Raman and
      CD spectra proved secondary structure alteration of BSA in the presence of MNPs.

PMID- 19583233
TI  - Enhanced protein steering: cooperative electrostatic and van der Waals forces in
      antigen-antibody complexes.
AB  - We study the association of the cationic protein lysozyme with several almost
      neutral protein fragments but with highly uneven charge distributions. Using
      mesoscopic protein models, we show how electrostatic interactions can align or
      steer protein complexes into specific constellations dictated by the specific
      charge distributions of the interacting biomolecules. Including van der Waals
      forces significantly amplifies the electrostatically induced orientational
      steering at physiological solution conditions, demonstrating that different
      intermolecular interactions can work in a cooperative way in order to optimize
      specific biochemical mechanisms. Individually, the electrostatic and van der
      Waals interactions lead only to a relatively weak intermolecular alignment, but
      when combined, the effect increases significantly.

PMID- 19583236
TI  - Water-chloride and water-bromide hydrogen-bonded networks: influence of the
      nature of the halide ions on the stability of the supramolecular assemblies.
AB  - Two compounds, namely, [TTPH(2)](Cl)(2) x 4 H(2)O (1) and [TTPH(2)](Br)(2) x 4
      H(2)O (2), (TTP = 4'-p-tolyl-2,2':6',2''-terpyridine) were synthesized from
      purely aqueous media and characterized by physical techniques. In the solid-state
      structures of these compounds, interesting supramolecular assemblies are
      observed. In 1, an unusual staircase-like architecture of the tape of edge-shared
      planar water hexamer is of importance, where the chloride ions are at the two
      edges of the tape. In 2, the polymeric nature of the water-bromide assembly is of
      interest, where discrete open-cube water octamers are doubly bridged by bromide
      ions. Semiempirical and DFT calculations confirm that the nature of the anion
      indeed affects the topology of the water-halide assemblies. We conclude that the
      protonated [TTPH(2)](2+) species can act as appropriate receptors for halide
      ions, which in turn act as a matrix for the formation of polymeric 1D water
      halide assemblies.

PMID- 19583237
TI  - Optoelectronic properties of natural cyanin dyes.
AB  - An integrated theoretical/experimental study of the natural cyanin dye is
      presented in terms of its structural and optoelectronic properties for different
      gas-phase and prototypical device configurations. Our microscopic analysis
      reveals the impact of hydration and hydroxylation reactions, as well as of the
      attached sugar, on ground and optically excited states, and it illustrates the
      visible-light harvesting capability of the dye. Our optical experiments at
      different and controlled pH concentrations allow for a direct comparison with
      theoretical results. We analyze the many different contributions to photocurrent
      of the various portions of a prototypical device and, as a proof of principle, we
      propose the addition of specific ligands to control the increase of the
      photocurrent yield in the cyanin-based electrochemical device.

PMID- 19583238
TI  - Computational insights into the mechanism of ligand unbinding and selectivity of
      estrogen receptors.
AB  - Estrogen receptors (ER) belong to the nuclear receptor superfamily, and two
      subtypes, ERalpha and ERbeta, have been identified to date. The differentiated
      functions and receptor expressions of ERalpha and ERbeta made it attracted to
      discover subtype-specified ligands with high selectivity. However, these two
      subtypes are highly homologous and only two residues differ in the ligand binding
      pocket. Therefore, the mechanism of ligand selectivity has become an important
      issue in searching selective ligands of ER subtypes. In this study, steered
      molecular dynamics simulations were carried out to investigate the unbinding
      pathways of two selective ERbeta ligands from the binding pocket of both ERalpha
      and ERbeta, which demonstrated that the pathway between the H11 helix and the H7
      approximately H8 loop was the most probable for ligand escaping. Then potentials
      of mean force for ligands unbinding along this pathway were calculated in order
      to gain insights into the molecular basis for energetics of ligand unbinding and
      find clues of ligand selectivity. The results indicated that His524/475 in
      ERalpha/ERbeta acted as a "gatekeeper" during the ligand unbinding. Especially,
      the H7 approximately H8 loop of ERbeta acted as a polar "transmitter" that
      controlled the ligand unbinding from the binding site and contributed to the
      ligand selectivity. Finally, the mechanism of ligand selectivity of ER subtypes
      was discussed from a kinetic perspective and suggestions for improving the ligand
      selectivity of ERbeta were also presented. These findings could be helpful for
      rational design of highly selective ERbeta ligands.

PMID- 19583241
TI  - Binding and release of consensus peptides by poly(acrylic acid) microgels.
AB  - The interaction between positively charged consensus peptides and poly(acrylic
      acid) microgels was investigated with micromanipulator-assisted light microscopy
      and confocal laser scanning microscopy. Peptide binding and release was monitored
      by microgel deswelling and swelling for monodisperse multiples of heparin-binding
      Cardin and Weintraub motifs, (AKKARA)(n) (1 <or= n <or= 4) and (ARKKAAKA)(n) (1
      <or= n <or= 3), as well as the corresponding titratable (AHHAHA)(4) and
      (AHHHAAHA)(3) peptides (A, K, R and H, refering to alanine, lysine, arginine, and
      histidine, respectively). When fully charged, these peptides distribute
      homogenously throughout the microgels and display concentration-dependent
      deswelling, which increases with increasing peptide length. Both (AKKARA)(4) and
      (ARKKAAKA)(3) display potent and fast microgel deswelling but only marginal
      subsequent electrolyte-induced desorption. In contrast, reducing the peptide
      charge for (AHHAHA)(4) and (AHHHAAHA)(3) at neutral and high pH, or the peptide
      length, substantially reduces the peptide affinity for the microgels and
      facilitates rapid peptide release. Taken together, the results also show that
      quite short peptides of moderate charge density interact strongly and cause
      extensive gel deswelling of oppositely charged microgels, precluding peptide
      release. They also show, however, that desirable triggered release can be
      achieved with peptides of lower charge density.

PMID- 19583242
TI  - Nitric oxide release in human aortic endothelial cells mediated by delivery of
      amphiphilic polysiloxane nanoparticles to caveolae.
AB  - Microdomains such as lipid raft and caveolae are organized as functional
      compartments in plasma membrane of cells. In this study, we note the functional
      platform of caveolae with dual functions, internalization of external substances
      and cell signalings leading to nitric oxide release, and hypothesize that the
      switching of enzyme activity of endothelial nitric oxide synthase can be achieved
      by targeting caveolae with nanoparticles. We prepared polysiloxane nanoparticles
      and studied cellular uptake of the nanoparticles and its concomitant influence on
      the nitric oxide release in human aortic endothelial cells. We found that
      polysiloxane nanoparticles were endocytosed via caveolae in human aortic
      endothelial cells and that enhanced nitric oxide release was followed by the
      cellular uptake of the nanoparticles. Furthermore, we confirmed that endothelial
      nitric oxide synthase was activated during cellular uptake of the nanoparticles.
      These findings support our idea that delivery of the polymeric nanoparticles to
      endothelial cells can lead to the induction of nitric oxide release.

PMID- 19583240
TI  - The role of ganglioside GM1 in cellular internalization mechanisms of
      poly(amidoamine) dendrimers.
AB  - Generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers with amine, acetamide, and
      carboxylate end groups were prepared to investigate polymer/cell membrane
      interactions in vitro. G7 PAMAM dendrimers were used in this study because higher
      generation of dendrimers are more effective in permeabilization of cell plasma
      membranes and in the formation of nanoscale holes in supported lipid bilayers
      than smaller, lower-generation dendrimers. Dendrimer-based conjugates were
      characterized by (1)H NMR, UV/vis spectroscopy, GPC, HPLC, and CE. Positively
      charged amine-terminated G7 dendrimers (G7-NH(2)) were observed to internalize
      into KB, Rat2, and C6 cells at a 200 nM concentration. By way of contrast,
      neither negatively charged G7 carboxylate-terminated dendrimers (G7-COOH) nor
      neutral acetamide-terminated G7 dendrimers (G7-Ac) associated with the cell
      plasma membrane or internalized under similar conditions. A series of in vitro
      experiments employing endocytic markers cholera toxin subunit B (CTB),
      transferrin, and GM(1)-pyrene were performed to further investigate mechanisms of
      dendrimer internalization into cells. G7-NH(2) dendrimers colocalized with CTB;
      however, experiments with C6 cells indicated that internalization of G7-NH(2) was
      not ganglioside GM(1) dependent. The G7/CTB colocalization was thus ascribed to
      an artifact of direct interaction between the two species. The presence of GM(1)
      in the membrane also had no effect upon XTT assays of cell viability or lactate
      dehydrogenase (LDH) assays of membrane permeability.

PMID- 19583243
TI  - Ultrafast differential ion mobility spectrometry at extreme electric fields in
      multichannel microchips.
AB  - The maximum electric field intensity (E) in field asymmetric waveform ion
      mobility spectrometry (FAIMS) analyses was doubled to E > 60 kV/cm. In earlier
      devices with >0.5 mm gaps, such strong fields cause electrical breakdown for
      nearly all gases at ambient pressure. As the Paschen curves are sublinear,
      thinner gaps permit higher E: here, we established 61 kV/cm in N(2) using
      microchips with 35 microm gaps. As FAIMS efficiency is exceptionally sensitive to
      E, such values can in theory accelerate analyses at equal resolution by over an
      order of magnitude. Here we demonstrate FAIMS filtering in approximately 20
      micros or approximately 1% of the previously needed time, with a resolving power
      of about half that for "macroscopic" units but sufficing for many applications.
      Microscopic gaps enable concurrent ion processing in multiple (here, 47)
      channels, which greatly relaxes the charge capacity constraints of planar FAIMS
      designs. These chips were integrated with a beta-radiation ion source and charge
      detector. The separation performance is in line with first-principles modeling
      that accounts for high-field and anisotropic ion diffusion. By extending FAIMS
      operation into the previously inaccessible field range, the present instrument
      advances the capabilities for research into ion transport and expands options for
      separation of hard-to-resolve species.

PMID- 19583245
TI  - Octanuclear aluminum(III) and iron(III) phosphonate cages encapsulating two Na(I)
      ions.
AB  - Hydrothermal reactions of aluminum(III) nitrate or iron(III) nitrate with N,N
      dimethylaminomethane-1,1-diphosphonic acid (H(4)L) and sodium hydroxide lead to
      two novel isostructural octanuclear metal phosphonate cages encapsulating two
      Na(I) ions, namely, [Al(8)Na(2)(HL)(2)(H(2)L)(10)(H(2)O)(6)] x 20 H(2)O (1) and
      [Fe(8)Na(2)(HL)(2)(H(2)L)(10)(H(2)O)(6)] x 22 H(2)O (2). The molecular structure
      of 1 can be viewed as a three-in-one cluster, in which a central zeolite D6R SBU
      lookalike aluminophosphonate cage is capped by two symmetry-related
      aluminophosphonate tetrahedral cages above and below and such a tetrahedral cage,
      being composed of four zeolite S6R SBU lookalike aluminophosphonate rings,
      further hexadentately traps one Na(+) ion in its cavity.

PMID- 19583244
TI  - The role of calcium in lipoprotein release by the low-density lipoprotein
      receptor.
AB  - The LDL receptor (LDLR) mediates efficient endocytosis of VLDL, VLDL remnants,
      and LDL. As part of the uptake process, the LDLR releases lipoproteins in
      endosomes. Released lipoproteins are subsequently trafficked to lysosomes for
      degradation, while the LDLR recycles back to the cell surface for further rounds
      of uptake. Endosomes have at least two features that can promote lipoprotein
      release: an acidic pH and low concentrations of free calcium. The relative
      contributions of acidic pH and low free calcium to lipoprotein release are not
      known. Here, we generated fibroblasts that express either normal LDLR or an LDLR
      variant that is unable to employ the acid-dependent release mechanism to
      determine the relative contributions of acidic pH and low free calcium on
      lipoprotein release. We show that endosomal concentrations of free calcium can
      drive lipoprotein release at rates that are similar to those of acid-dependent
      release and that the calcium-dependent and acid-dependent mechanisms can
      cooperate during lipoprotein release. Assessment of lipoprotein uptake by these
      two cell lines showed that LDL uptake requires the acid-dependent mechanism,
      while uptake of the VLDL remnant, beta-VLDL, does not. We propose that endosomes
      use both the acid-dependent and calcium-dependent release mechanisms to drive
      lipoprotein release and that the acid-dependent process is only required for LDL
      release.

PMID- 19583246
TI  - Current versus temperature-induced switching in a single-molecule tunnel
      junction: 1,5 cyclooctadiene on Si(001).
AB  - The biconformational switching of single cyclooctadiene molecules chemisorbed on
      a Si(001) surface was explored by quantum chemical and quantum dynamical
      calculations and low-temperature scanning tunneling microscopy experiments. The
      calculations rationalize the experimentally observed switching driven by
      inelastic electron tunneling (IET) at 5 K. At higher temperatures, they predict a
      controllable crossover behavior between IET-driven and thermally activated
      switching, which is fully confirmed by experiment.

PMID- 19583247
TI  - Ligand and solvation effects on the electronic properties of Au55 clusters: a
      density functional theory study.
AB  - The electronic properties of the neutral, positively and negatively charged bare
      Au(55), passivated Au(55)(PH(3))(12), Au(55)(PH(3))(12)Cl(6), and solvated
      Au(55)(PH(3))(12)Cl(6) 54 H(2)O clusters are studied using density functional
      theory. The presence of Cl atoms in the ligand shell favors a nonmetallic
      behavior while a more metallic behavior is induced by explicit solvation of
      Au(55)(PH(3))(12)Cl(6) with water molecules. The trends observed in the
      electronic properties upon ligation and solvation are in agreement with
      experimental studies.

PMID- 19583248
TI  - Enhanced permeability of charged dendrimers across tense lipid bilayer membranes.
AB  - Dendrimers have successfully proved themselves as functional nanodevices for drug
      delivery because they can render drug molecules a greater water solubility,
      bioavailability, and biocompatibility. It has recently been suggested that the
      structural changes of cell membranes (e.g., local lipid density and actual pore
      or hole) could affect the permeability across them for dendrimers. However, to
      understand these effects requires direct measurements in a single cell and is
      thus very difficult and more challenging. Here we use mesoscopic simulations to
      investigate the tension-mediated complexes comprising charged dendrimers and
      lipid bilayer membranes. The structures of membranes are alternated by adjusting
      their surface tensions. Our simulations demonstrate that the permeability of
      charged dendrimers can be effectively enhanced in the tense membranes, and the
      permeability in the actual hole is several times higher than that in the lipid
      poor section. The possible mechanism of charged dendrimer-induced pore nucleation
      in the tense membranes is evaluated. The findings have implications in tuning
      intracellular delivery rates and amounts in nanoscale complex and
      chemotherapeutics.

PMID- 19583249
TI  - Shear and AC Field Enhanced Carbon Nanotube Impedance Assay for Rapid, Sensitive,
      and Mismatch-Discriminating DNA Hybridization.
AB  - Other than concentrating the target molecules at the sensor location, we
      demonstrate two distinct new advantages of an open-flow impedance-sensing
      platform for DNA hybridization on carbon nanotube (CNT) surface in the presence
      of a high-frequency AC electric field. The shear-enhanced DNA and ion transport
      rate to the CNT surface decouples the parasitic double-layer AC impedance signal
      from the charge-transfer signal due to DNA hybridization. The flow field at high
      AC frequency also amplifies the charge-transfer rate across the hybridized CNT
      and provides shear-enhanced discrimination between DNA from targeted species and
      a closely related congeneric species with three nucleotide mismatches out of 26
      bases in a targeted attachment region. This allows sensitive detection of
      hybridization events in less than 20 min with picomolar target DNA concentrations
      in a label-free CNT-based microfluidic detection platform.

PMID- 19583250
TI  - Effect of temperature on the capacitance of carbon nanotube supercapacitors.
AB  - The effect of temperature on the kinetics and the diffusion mechanism of the ions
      in a supercapacitor assembled with single-walled carbon nanotube (SWNT) film
      electrodes and an organic electrolyte were thoroughly investigated. An improved
      room temperature performance of the supercapacitor was observed due to the
      combined effects of an increase in the conductivity of the SWNT films and surface
      modifications on the SWNT films by repeatedly heating and cooling the
      supercapacitor between the temperatures of 25 and 100 degrees C. Modified Randles
      equivalent circuit was employed to carry out an extensive analysis of the Nyquist
      spectra measured at different temperatures between 25 and 100 degrees C in order
      to understand the fundamentals of the capacitive and resistive variations in the
      supercapacitor. The experimental results and their thorough analysis will have
      significant impact not only on the fundamental understanding of the temperature
      dependent electrode/electrolyte interfacial properties but also on supercapacitor
      design with appropriate electrode materials for numerous industrial and consumer
      applications. The supercapacitor with SWNT film electrodes was capable of
      withstanding current densities as high as 100 A/g, yielding eminent specific
      power density values of about 55 kW/kg. Ultralong galvanostatic charge-discharge
      cycling over 200 000 cycles with a constant current density of 20 A/g at 25 and
      100 degrees C, respectively, showed excellent stability in capacitance with more
      than 80% efficiency. The usage of such a supercapacitor potentially enables far
      reaching advances in backup energy storage and high pulse power applications.

PMID- 19583251
TI  - Rolloamides A and B, cytotoxic cyclic heptapeptides isolated from the Caribbean
      marine sponge Eurypon laughlini.
AB  - Two cyclic heptapeptides, rolloamides A (1) and B (2), have been isolated from
      the Dominican marine sponge Eurypon laughlini. The structures of 1 and 2 were
      elucidated by a combination of spectroscopic analyses and chemical degradation.
      Rolloamide A (1), which was found to exist as two distinct conformers in
      C(5)D(5)N, exhibits growth suppressive activity against a panel of histologically
      diverse cancer cell lines.

PMID- 19583252
TI  - Anti-inflammatory flavonoids from the rhizomes of Helminthostachys zeylanica.
AB  - Eight new prenylated flavonoids, ugonins M-T (1-8), together with five known
      compounds, ugonins J-L (9-11), 5,4'-dihydroxy-4'',4''-dimethyl-5''-methyl-5''H
      dihydrofurano[2'',3'':6,7]flavanone, and quercetin, were isolated and purified
      from the rhizomes of Helminthostachys zeylanica. The structures of the new
      isolates were elucidated by spectroscopic and chemical methods. Compounds 1, 3,
      5, 7, 8, and 11 showed inhibition of superoxide anion generation and elastase
      release by human neutrophils in response to formyl-l-methionyl-l-leucyl-l
      phenylalanine/cytochalasin B (FMLP/CB).

PMID- 19583253
TI  - Surface Raman spectroscopy of the interface of tris-(8-hydroxyquinoline) aluminum
      with Mg.
AB  - Surface Raman spectroscopy in ultrahigh vacuum is used to interrogate interfaces
      formed between tris-(8-hydroxyquinoline) aluminum (Alq(3)) and vapor-deposited
      Mg. The Raman spectral results for deposition of Mg mass thicknesses between 5
      and 20 A indicate formation of a complex interfacial region composed primarily of
      Mg-Alq(3) adducts and small-grained amorphous or nanocrystalline graphite, the
      presence of which may have a significant effect on the electronic properties of
      this metal-organic interface. The observed shifts in nu(ring), nu(C-N), nu(Al-N),
      and nu(Al-O) modes along with the appearance of nu(Mg-C) and nu(Mg-O) modes
      suggest a structure for the Mg-Alq(3) adduct in which Mg is bound to the O and C
      atoms of Alq(3). In addition, several intense, broad modes are observed that are
      consistent with partial graphitization of the Alq(3) film.

PMID- 19583254
TI  - FLEth RNA intercalating probe is a convenient reporter for small interfering
      RNAs.
AB  - Here we report that the phenanthridine derivative covalently linked to a
      fluorescein moiety (FLEth) can act as a fluorescence based probe for duplex short
      interfering RNA (siRNA) and that this probe can also be used to report on protein
      RNA interactions. A fluorescence resonance energy transfer (FRET) signal that is
      observed at 600 nm occurs when FLEth is complexed with siRNA. At least 2
      molecules of FLEth can bind to 21 nt duplex siRNA, and the dissociation constants
      for these interactions are reported. We find that FLEth can also report on the
      interaction of siRNAs with the Carnation Italian ringspot viral suppressor of RNA
      silencing p19. FLEth does not bind to the siRNA-p19 complex nor can p19 bind to
      the siRNA-FLEth complex; rather FLEth can report on the fraction of siRNA that is
      unbound. FLEth can also bind siRNA in delivery systems such as liposomes. Once
      the siRNA reaches the interior of Huh 7.5 cells, FLEth dissociates from the siRNA
      and is found in the nucleoli suggesting that FLEth cannot bind to siRNAs that are
      associated with the RNA silencing machinery.

PMID- 19583255
TI  - Sortase-catalyzed peptide-glycosylphosphatidylinositol analogue ligation.
AB  - It is demonstrated that sortase A (SrtA) can catalyze efficient coupling of
      peptides to GPI analogues with a glycine residue attached to the
      phosphoethanolamine moiety at the nonreducing end to form GPI-linked peptides.
      This represents the first chemoenzymatic synthesis of GPI-peptide conjugates and
      is a proof-of-concept for the potential application of SrtA to the synthesis of
      more complex GPI-anchored peptides/glycopeptides and GPI-anchored
      proteins/glycoproteins.

PMID- 19583256
TI  - Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant
      potential and protective effects against H2O2-induced oxidative damage to pBR322
      DNA and red blood cells.
AB  - We evaluated the protective effects of subfractions of the ethyl acetate fraction
      (EAF) and the methanolic fraction (MF) from the crude ethanolic extract (CEE) of
      Azadirachta indica A. Juss (neem) leaves against various free radicals and
      hydrogen peroxide (H2O2)-induced oxidative damage to red blood cells (RBCs) and
      pBR322 DNA. Neem leaf fractions reduced DPPH(*), ABTS(*+), superoxide (O(*-)),
      hydroxyl (OH(*)), and nitric oxide radicals to nonradical forms in a
      concentration-dependent manner. Treatment with the benzene insoluble fraction
      from EAF (EBIF), the chloroform insoluble fraction from EAF (ECIF), the
      chloroform insoluble fraction from MF (MCIF), and the ethyl acetate insoluble
      fraction from MF (MEIF) significantly mitigated H2O2-induced oxidative damage to
      RBCs and pBR322 DNA. Although we found low in vitro free radical scavenging
      activity for the benzene insoluble fraction from EAF (EBSF), the chloroform
      soluble fraction from EAF (ECSF), the chloroform soluble fraction from MF (MCSF),
      and the ethyl acetate soluble fraction from MF (MESF), these fractions showed no
      effect on H2O2-induced lipid peroxidation and pBR322 DNA damage. High-performance
      liquid chromatography (HPLC) and TLC-Iatroscan analysis revealed that the greater
      efficacy of EBIF, ECIF, MCIF, and MEIF may be due to the presence of more polar
      compounds such as nimbolide and quercetin. Our studies suggest that the
      antioxidant and protective effects of active neem leaf fractions against H2O2
      induced lipid peroxidation and pBR322 DNA damage can be attributed to their
      ability to inhibit various free radicals.

PMID- 19583258
TI  - Metal-organic frameworks impregnated with magnesium-decorated fullerenes for
      methane and hydrogen storage.
AB  - A new concept is described for methane and hydrogen storage materials involving
      the incorporation of magnesium-decorated fullerenes within metal-organic
      frameworks (MOFs). The system is modeled using a novel approach underpinned by
      surface potential energies developed from Lennard-Jones parameters. Impregnation
      of MOF pores with magnesium-decorated Mg(10)C(60) fullerenes, denoted as Mg
      C(60)@MOF, places exposed metal sites with high heats of gas adsorption into
      intimate contact with large surface area MOF structures. Perhaps surprisingly,
      given the void space occupied by C(60), this impregnation delivers remarkable gas
      uptake, according to our modeling, which predicts exceptional performance for the
      Mg-C(60)@MOF family of materials. These predictions include a volumetric methane
      uptake of 265 v/v, the highest reported value for any material, which
      significantly exceeds the U.S. Department of Energy target of 180 v/v. We also
      predict a very high hydrogen adsorption enthalpy of 11 kJ mol(-1) with relatively
      little decrease as a function of H(2) filling. This value is close to the
      calculated optimum value of 15.1 kJ mol(-1) and is achieved concurrently with
      saturation hydrogen uptake in large amounts at pressures under 10 atm.

PMID- 19583257
TI  - A suite of activity-based probes for human cytochrome P450 enzymes.
AB  - Cytochrome P450 (P450) enzymes regulate a variety of endogenous signaling
      molecules and play central roles in the metabolism of xenobiotics and drugs. We
      recently showed that an aryl alkyne serves as an effective activity-based probe
      for profiling mouse liver microsomal P450s in vitro and in vivo. However,
      individual P450s display distinct substrate and inhibitor specificities,
      indicating that multiple probe structures may be required to achieve
      comprehensive coverage of this large and diverse enzyme family. Here, we have
      synthesized a suite of P450-directed, activity-based protein profiling (ABPP)
      probes that contain: (1) varied chemical architectures validated as mechanism
      based inhibitors of the P450 enzyme family, and (2) terminal alkyne groups for
      click chemistry conjugation of reporter tags. This set of probes was screened
      against a wide cross-section of human P450s, leading to the discovery of an
      optimal set of probes that provide broad coverage of this enzyme family. We used
      these probes to profile the effects on P450 activity of aromatase inhibitors in
      current clinical use for the treatment of breast cancer. We describe the
      surprising discovery that one of these aromatase inhibitors, anastrozole,
      significantly increases probe-labeling of P450 1A2, indicative of a heterotypic
      cooperativity effect on a central P450 isozyme involved in metabolizing numerous
      drugs and xenobiotics. The results presented herein greatly expand the suite of
      ABPP probes for profiling P450s and illuminate new applications for these tools
      to understand P450-drug interactions.

PMID- 19583259
TI  - Mechanisms of DNA binding and regulation of Bacillus anthracis DNA primase.
AB  - DNA primases are pivotal enzymes in chromosomal DNA replication in all organisms.
      In this article, we report unique mechanistic characteristics of recombinant DNA
      primase from Bacillus anthracis. The mechanism of action of B. anthracis DNA
      primase (DnaG(BA)) may be described in several distinct steps as follows. Its
      mechanism of action is initiated when it binds to single-stranded DNA (ssDNA) in
      the form of a trimer. Although DnaG(BA) binds to different DNA sequences with
      moderate affinity (as expected of a mobile DNA binding protein), we found that
      DnaG(BA) bound to the origin of bacteriophage G4 (G4ori) with approximately 8
      fold higher affinity. DnaG(BA) was strongly stimulated (>or=75-fold) by its
      cognate helicase, DnaB(BA), during RNA primer synthesis. With the G4ori ssDNA
      template, DnaG(BA) formed short (<or=20 nucleotides) primers in the absence of
      DnaB(BA). The presence of DnaB(BA) increased the rate of primer synthesis. The
      observed stimulation of primer synthesis by cognate DnaB(BA) is thus indicative
      of a positive effector role for DnaB(BA). By contrast, Escherichia coli DnaB
      helicase (DnaB(EC)) did not stimulate DnaG(BA) and inhibited primer synthesis to
      near completion. This observed effect of E. coli DnaB(EC) is indicative of a
      strong negative effector role for heterologous DnaB(EC). We conclude that
      DnaG(BA) is capable of interacting with DnaB proteins from both B. anthracis and
      E. coli; however, between DnaB proteins derived from these two organisms, only
      the homologous DNA helicase (DnaB(BA)) acted as a positive effector of primer
      synthesis.

PMID- 19583260
TI  - Synthesis and in vitro evaluation of N-substituted maleimide derivatives as
      selective monoglyceride lipase inhibitors.
AB  - The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many
      physiological processes, and its action is quickly terminated via enzymatic
      hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous
      level could offer therapeutic opportunities; however, few selective MGL
      inhibitors have been described so far. Here, we describe the synthesis of N
      substituted maleimides and their pharmacological evaluation on the recombinant
      human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N
      arylmaleimides were previously described ( Saario , S. M. ; Salo , O. M. ;
      Nevalainen , T. ; Poso , A. ; Laitinen , J. T. ; Jarvinen , T. ; Niemi , R.
      Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for
      Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes . Chem. Biol.
      2005 , 12 , 649 - 656 ) as MGL inhibitors, and along these lines, we present a
      new set of maleimide derivatives that showed low micromolar IC(50) and high
      selectivity toward MGL vs FAAH. Then, structure-activity relationships have been
      investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with
      an IC(50) value of 790 nM. Furthermore, rapid dilution experiments reveal that
      these compounds act as irreversible inhibitors. In conclusion, N-substituted
      maleimides constitute a promising class of potent and selective MGL inhibitors.

PMID- 19583261
TI  - The hypervariable region of K-Ras4B is responsible for its specific interactions
      with calmodulin.
AB  - K-Ras4B belongs to the family of p21 Ras GTPases, which play an important role in
      cell proliferation, survival, and motility. The p21 Ras proteins, such as K
      Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very
      similar signaling pathways. Only the C-terminal hypervariable regions differ
      significantly. A growing body of literature demonstrates that each Ras isoform
      possesses unique functions in normal physiological processes as well as in
      pathogenesis. One of the central questions in the field of Ras biology is how
      these very similar proteins achieve such remarkable specificity in protein
      protein interactions that regulate signal transduction pathways. Here we explore
      specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal
      titration calorimetry, we demonstrate that the hypervariable region of K-Ras4B
      contributes in a major way to the interaction with calmodulin, while the
      catalytic domain of K-Ras4B provides a way to control the interaction by
      nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the
      C-terminal domain of Ca(2+)-loaded calmodulin with micromolar affinity, while the
      GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal
      domain of calmodulin.

PMID- 19583262
TI  - Characterization of an RNA-cleaving deoxyribozyme with optimal activity at pH 5.
AB  - An in vitro selection endeavor previously executed by our laboratory led to the
      isolation of a set of RNA-cleaving deoxyribozymes that thrive under acidic
      conditions [Liu, Z., Mei, S. H., Brennan, J. D., and Li, Y. (2003) J. Am. Chem.
      Soc. 125, 7539-7545]. One of these sequences, coined pH5DZ1, is a 100-nucleotide
      (nt) cis-acting enzyme that was found to exhibit high cleavage activity near pH
      5. Herein, we seek to deduce the properties and sequence requirements of this
      enzyme. This deoxyribozyme was found to cleave a 23-nt chimeric DNA-RNA
      substrate, which contains a single ribonucleotide flanked by fluorophore- and
      quencher-modified nucleotides on each side of the cleavage junction. Extensive
      nucleotide deletion experiments indicated that only 42 bases within the original
      enzyme sequence are required for catalysis. Results from a reselection experiment
      further revealed that 26 of these nucleotides are absolutely conserved. In
      addition to sequence analysis and minimization studies, we successfully designed
      a trans-acting variant of this enzyme. Characterization of the cleavage products
      produced upon pH5DZ1-mediated RNA cleavage and analyses of possible structures of
      pH5DZ1 provided us with insights into the catalytic mechanism of pH5DZ1 and
      characteristics of deoxyribozymes that retain their activity under acidic
      conditions.

PMID- 19583279
TI  - Electrical and photoresponse properties of an intramolecular p-n homojunction in
      single phosphorus-doped ZnO nanowires.
AB  - The single-crystal n-type and p-type ZnO nanowires (NWs) were synthesized via a
      chemical vapor deposition method, where phosphorus pentoxide was used as the
      dopant source. The electrical and photoluminescence studies reveal that
      phosphorus-doped ZnO NWs (ZnO:P NWs) can be changed from n-type to p-type with
      increasing P concentration. Furthermore, we report for the first time the
      formation of an intramolecular p-n homojunction in a single ZnO:P NW. The p-n
      junction diode has a high on/off current ratio of 2.5 x 10(3) and a low forward
      turn-on voltage of approximately 1.37 V. Finally, the photoresponse properties of
      the diode were investigated under UV (325 nm) excitation in air at room
      temperature. The high photocurrent/dark current ratio (3.2 x 10(4)) reveals that
      the diode has a potential as extreme sensitive UV photodetectors.

PMID- 19583280
TI  - Recombination dynamics of spatially confined electron-hole system in luminescent
      gold catalyzed silicon nanowires.
AB  - We study by time-resolved low temperature photoluminescence (PL) experiments of
      the electronic states of silicon nanowires (SiNWs) grown by gold catalyzed
      chemical vapor deposition and passivated by thermal SiO(2). The typical
      recombination line of free carriers in gold-catalyzed SiNWs (Au-SiNWs) is
      identified and studied by time-resolved experiments. We demonstrate that
      intrinsic Auger recombination governs the recombination dynamic of the dense e-h
      plasma generated inside the NW. In a few tens of nanoseconds after the pulsed
      excitation, the density of the initial electronic system rapidly decreases down
      to reach that of a stable electron-hole liquid phase. The comparison of the PL
      intensity decay time of Au-SiNWs with high crystalline quality and purity silicon
      layer allows us to conclude that the Au-SiNW electronic properties are highly
      comparable to those of bulk silicon crystal.

PMID- 19583281
TI  - Comparison of epitaxial graphene on Si-face and C-face 4H SiC formed by ultrahigh
      vacuum and RF furnace production.
AB  - We present X-ray photoelectron spectroscopy, van der Pauw Hall mobilities, low
      temperature far-infrared magneto transmission (FIR-MT), and atomic force
      microscopy (AFM) results from graphene films produced by radiative heating in an
      ultrahigh vacuum (UHV) chamber or produced by radio frequency (RF) furnace
      annealing in a high vacuum chemical vapor deposition system on Si- and C-face 4H
      SiC substrates at 1200-1600 degrees C. Although the vacuum level and heating
      methods are different, graphene films produced by the two methods are chemically
      similar with the RF furnace annealing typically producing thicker graphene films
      than UHV. We observe, however, that the formation of graphene on the two faces is
      different with the thicker graphene films on the C-face RF samples having higher
      mobility. The FIR-MT showed a 0(-1) --> 1(0) Landau level transition with a
      square root B dependence and a line width consistent with a Dirac fermion with a
      mobility >250,000 cm(2) x V(-1) x s(-1) at 4.2 K in a C-face RF sample having a
      Hall-effect carrier mobility of 425 cm(2) x V(-1) x s(-1) at 300 K. AFM shows
      that graphene grows continuously over the varying morphology of both Si and C
      face substrates.

PMID- 19583282
TI  - Toward multiprotein nanoarrays using nanografting and DNA directed immobilization
      of proteins.
AB  - Atomic force microscopy nanografting was utilized to prepare DNA nanopatches of
      different sizes (200 x 200 to 1000 x 1000 nm(2)) onto which DNA-protein
      conjugates can be anchored through DNA-directed immobilization. Height
      measurements were used to assess the binding of the proteins as well as their
      subsequent interaction with other components, such as antibodies. The results
      indicate that nanografted patch arrays are well suited for application in
      biosensing and could enable the fabrication of multifeature protein nanoarrays.

PMID- 19583284
TI  - Electron-beam-induced deposition of platinum from a liquid precursor.
AB  - We demonstrate here the first focused electron-beam-induced deposition (EBID) of
      nanostructures using a liquid precursor. We have deposited sub-50 nm platinum
      (Pt) wires and dots from a dilute, aqueous solution of chloroplatinic acid.
      Existing EBID processes rely on the electron-beam stimulated decomposition of
      gaseous precursors; as a result, the deposits are highly contaminated (up to 75
      at. % carbon or 60 at. % phosphorus for Pt processes). In contrast, we show that
      deposition of platinum by electron-beam reduction of platinum ions from solution
      leads to high-purity deposits (approximately 10 at. % chlorine contamination) at
      rates at least ten times higher than those obtained with other platinum
      precursors. Liquid-phase EBID offers a new route to deterministic, three
      dimensional, nanometer-scale structures composed of multiple materials without
      complex multistep processing. Thus, it may prove important for prototyping and
      low-volume production of nanoscale devices and for repair and modification of
      nanoscale masks and templates used in high-volume production.

PMID- 19583283
TI  - Direct-bandgap InAs quantum-dots have long-range electron-hole exchange whereas
      indirect gap Si dots have short-range exchange.
AB  - Excitons in quantum dots manifest a lower-energy spin-forbidden "dark" state
      below a spin-allowed "bright" state; this splitting originates from electron-hole
      (e-h) exchange interactions, which are strongly enhanced by quantum confinement.
      The e-h exchange interaction may have both a short-range and a long-range
      component. Calculating numerically the e-h exchange energies from atomistic
      pseudopotential wave functions, we show here that in direct-gap quantum dots
      (such as InAs) the e-h exchange interaction is dominated by the long-range
      component, whereas in indirect-gap quantum dots (such as Si) only the short-range
      component survives. As a result, the exciton dark/bright splitting scales as
      1/R(2) in InAs dots and 1/R(3) in Si dots, where R is the quantum-dot radius.

PMID- 19583332
TI  - Accurately Probing Slow Motions on Millisecond Timescales with a Robust NMR
      Relaxation Experiment.

PMID- 19583303
TI  - Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in
      protein structure, stability, and solvent network.
AB  - Human carbonic anhydrase II (HCA II) is a monomeric zinc-containing metalloenzyme
      that catalyzes the hydration of CO(2) to form bicarbonate and a proton. The
      properties of the zinc have been extensively elucidated in catalysis but less
      well studied as a contributor to structure and stability. Apo-HCA II (without
      zinc) was prepared and compared to holo-HCA II: in crystallographic structural
      features, in backbone amide H/D exchange, and in thermal stability. The removal
      of zinc from the active site has no effect on either the topological fold of the
      enzyme or the ordered water network in the active site. However, the removal of
      the zinc alters the collective electrostatics of the apo-HCA II that result in
      the following differences from that of the holoenzyme: (1) the main thermal
      unfolding transition of the apo-HCA II is lowered by 8 degrees C, (2) the
      relative increase in thermal mobility of atoms of the apo-HCA II was not observed
      in the vicinity of the active site but manifested on the surface of the enzyme,
      and (3) the side chain of His 64, the proton shuttle residue that sits on the rim
      of the active site, is oriented outward and is associated with additional ordered
      "external" waters, as opposed to a near equal inward and outward orientation in
      the holo-HCA II.

PMID- 19583428
TI  - Introduction to cancer chemotherapeutics.

PMID- 19583429
TI  - ABC efflux pump-based resistance to chemotherapy drugs.

PMID- 19583430
TI  - Aldehyde selective Wacker oxidations of phthalimide protected allylic amines: a
      new catalytic route to beta3-amino acids.
AB  - A new method for the synthesis of beta(3)-amino acids is presented. Phthalimide
      protected allylic amines are oxidized under Wacker conditions selectively to
      aldehydes using PdCl(2) and CuCl or Pd(MeCN)(2)Cl(NO(2)) and CuCl(2) as
      complementary catalyst systems. The aldehydes are produced in excellent yields
      and exhibit a large substrate scope. Beta-amino acids and alcohols are
      synthesized by oxidation or reduction and subsequent deprotection.

PMID- 19583432
TI  - Bi3Mn3O11: a new KSbO3-type random ferrimagnet with high T(C).
AB  - A new compound, Bi(3)Mn(3)O(11), with a KSbO(3)-type structure was prepared using
      a high-pressure technique. Its structural, chemical, and magnetic properties have
      been investigated. Bi(3)Mn(3)O(11) was shown to be a ferrimagnet with rather high
      T(C) despite the random distribution of manganese ions with different oxidation
      states in one site. Bi(3)Mn(3)O(11) gradually loses oxygen on heating forming
      several phases with the same structure but with different magnetic properties.
      These findings may revive interest in the KSbO(3) family of compounds, which is
      rather adaptive considering the cation variations and oxygen content.

PMID- 19583431
TI  - Carborane-based pincers: synthesis and structure of SeBSe and SBS Pd(II)
      complexes.
AB  - We report the synthesis of several unique, boron-rich pincer complexes derived
      from m-carborane. The SeBSe and SBS pincer ligands can be synthesized via two
      independent synthetic routes and are metalated with Pd(II). These structures
      represent unique coordinating motifs, each with a Pd-B(2) bond chelated by two
      thio- or selenoether ligands. This class of structures serves as the first
      example of boron-metal pincer complexes and possesses several interesting
      electronic properties imposed by the m-carborane cage.

PMID- 19583433
TI  - Elucidating the mechanism of lipid membrane-induced IAPP fibrillogenesis and its
      inhibition by the red wine compound resveratrol: a synchrotron X-ray reflectivity
      study.
AB  - The islet amyloid polypeptide (IAPP) or amylin is a pancreatic hormone and
      crucially involved in the pathogenesis of type-II diabetes mellitus (T2DM).
      Aggregation and amyloid formation of IAPP is considered as the primary culprit
      for pancreatic beta-cell loss in T2DM patients. In this study, first X-ray
      reflectivity (XRR) measurements on IAPP at lipid interfaces have been carried
      out, providing a molecular level characterization of the first steps of the lipid
      induced fibrillation process of IAPP, which is initiated by lipid-induced
      nucleation, oligomerization, followed by detachment of larger IAPP aggregate
      structures from the lipid membrane, and terminated by the formation of mature
      fibrils in the bulk solution. The adsorption process of IAPP at lipid interfaces
      in the absence and presence of negatively charged lipid has also been studied by
      complementary ATR-FTIR spectroscopic measurements. The morphological properties
      were followed by atomic force microscopy (AFM). Moreover, we show that the
      polyphenolic red wine compound resveratrol is able to inhibit IAPP aggregation
      also in the presence of aggregation-fostering negatively charged lipid
      interfaces, revealing its potential as a drug candidate for T2DM.

PMID- 19583435
TI  - Advanced Monte Carlo approach to study evolution of quartz surface during the
      dissolution process.
AB  - A newly developed Monte Carlo (MC) algorithm designed to study the complex
      interplay of dissolution and precipitation reactions on mineral surface is
      presented. This algorithm utilizes existing advanced reactive and configurational
      biased MC techniques with new protocols specific for mineral-water interfaces.
      This time-independent methodology is especially advantageous for studying the
      kinetically slow quartz-water dissolution process. The aim is to use this method
      to understand the role of the local arrangement of reactive sites and surface
      topography in the surface evolution during dissolution. The simulations were
      performed in neutral pH medium, and two possible dissolution mechanisms were
      tested. The results indicate that out of the direct and stepwise mechanisms, the
      direct mechanism leads to complete dissolution that is not experimentally
      observed in the natural environment. On the other hand, the stepwise dissolution
      is more realistic, as it resembles the experimentally observed steady-state
      dissolution of the quartz-water system. These simulations identify the least
      coordinated surface sites (Q(1)) as the primary reactive site for hydrolysis and
      precipitation. Other surface sites (Q(2) and Q(3)) also undergo hydrolysis, but
      they are sterically hindered and are turned passive by precipitating Q(1) groups.
      The conclusions from the simulations are dominated by the surface topology of
      quartz; thus, we believe that the results are applicable for other polymorphs of
      silica and other protonation conditions.

PMID- 19583434
TI  - Determination of the solution-bound conformation of an amino acid binding protein
      by NMR paramagnetic relaxation enhancement: use of a single flexible paramagnetic
      probe with improved estimation of its sampling space.
AB  - We demonstrate the feasibility of elucidating the bound ("closed") conformation
      of a periplasmic binding protein, the glutamine-binding protein (GlnBP), in
      solution, using paramagnetic relaxation enhancements (PREs) arising from a single
      paramagnetic group. GlnBP consists of two globular domains connected by a hinge.
      Using the ligand-free ("open") conformation as a starting point, conjoined rigid
      body/torsion-angle simulated annealing calculations were performed using backbone
      (1)H(N)-PREs as a major source of distance information. Paramagnetic probe
      flexibility was accounted for via a multiple-conformer representation. A
      conventional approach where the entire PRE data set is enforced at once during
      simulated annealing yielded poor results due to inappropriate conformational
      sampling of the probe. On the other hand, significant improvements in coordinate
      accuracy were obtained by estimating the probe sampling space prior to structure
      calculation. Such sampling is achieved by refining the ensemble of probe
      conformers with intradomain PREs only, keeping the protein backbone fixed in the
      open form. Subsequently, while constraining the probe to the previously found
      conformations, the domains are allowed to move relative to each other under the
      influence of the non-intradomain PREs, giving the hinge region torsional degrees
      of freedom. Thus, by partitioning the protocol into "probe sampling" and
      "backbone sampling" stages, structures significantly closer to the X-ray
      structure of ligand-bound GlnBP were obtained.

PMID- 19583438
TI  - Intra-protein compensatory mutations analysis highlights the tRNA recognition
      regions in aminoacyl-tRNA synthetases.
AB  - The aminoacyl-tRNA synthetases (aaRSs) covalently attach amino acids to their
      corresponding nucleic acid adapter molecules, tRNAs. The interactions in the tRNA
      aaRSs complexes are mostly non-specific, and largely electrostatic. Tracing a way
      of aaRS-tRNA mutual adaptation throughout evolution offers a clearer view of
      understanding how aaRS-tRNA systems preserve patterns of tRNA recognition and
      binding. In this study, we used the compensatory mutations analysis to explore
      adaptation of aaRSs in respond to random mutations that can occur in the tRNA
      recognition area. We showed that the frequency of compensatory mutations among
      residues that belong to the recognition region is 1.75-fold higher than that of
      the exposed residues. The highest frequencies of compensatory mutations are
      observed for pairs of charged residues, wherein one residue is located within the
      tRNA-recognition area, while the second is placed outside of the area, and
      contributes to the formation of the aaRS electrostatic landscape. Given charged
      residues are compensated by buried charge residues in more than 60% of the
      analyzed mutations. The cytoplasmatic and mitochondrial aaRSs preserve similar
      patterns of compensatory mutations in the tRNA recognition areas. Moreover, we
      found that mitochondrial aaRSs demonstrate a significant increase in the
      frequency of compensatory mutations in the area. Our findings shed light on the
      physical nature of compensatory mutations in aaRSs, thereby keeping unchanged
      tRNA-recognition patterns.

PMID- 19583439
TI  - Structural rearrangements of rhodopsin subunits in a dimer complex: a molecular
      dynamics simulation study.
AB  - The present work reports a 0.1 micros molecular dynamics simulation of a bovine
      rhodopsin dimer based on a recently reported semi-empirical model obtained by
      fitting two monomers from the crystal structure to atomic force microscopy maps
      (Fotiadis et al. Curr Opin Struct Biol 16, 252, 2006). The simulation shows that
      the quaternary arrangement is stable although subtle rearrangements in its
      tertiary elements are observed during the first 60 ns of the trajectory. The
      comparison with a parallel 0.1 micros simulation of a single monomer in the same
      conditions and using the same protocol allows the study of subunit-subunit
      interactions on the dimer interface together with the structural effects
      associated to the dimer formation. The present study describes the interface of a
      TM4/TM5-TM4/TM5 dimer at an atomistic level including an analysis of the energy
      contributions to the interaction of each part of the protein involved. We also
      compare the differences in the structure of the single monomer with those of the
      dimer subunits with the aim of understanding the changes required for the dimer
      formation.

PMID- 19583437
TI  - tRNA-dependent cysteine biosynthetic pathway represents a strategy to increase
      cysteine contents by preventing it from thermal degradation: thermal adaptation
      of methanogenic archaea ancestor.
AB  - Although cysteine (Cys) is beneficial to stabilize protein structures, it is not
      prevalent in thermophiles. For instance, the Cys contents in most thermophilic
      archaea are only around 0.7%. However, methanogenic archaea, no matter
      thermophilic or not, contain relatively abundant Cys, which remains elusive for a
      long time. Recently, Klipcan et al. correlated this intriguing property of
      methanogenic archaea with their unique tRNA-dependent Cys biosynthetic pathway.
      But, the deep reasons underlying the correlation are ambiguous. Considering the
      facts that free Cys is thermally labile and the tRNA-dependent Cys biosynthesis
      avoids the use of free Cys, we speculate that the unique Cys biosynthetic pathway
      represents a strategy to increase Cys contents by preventing it from thermal
      degradation, which may be relevant to the thermal adaptation of methanogenic
      archaea ancestor.

PMID- 19583441
TI  - Studies on the structural stability of rabbit prion probed by molecular dynamics
      simulations.
AB  - Prion diseases are invariably fatal and highly infectious neurodegenerative
      diseases that affect humans and animals. Rabbits are the only mammalian species
      reported to be resistant to infection from prion diseases isolated from other
      species (I. Vorberg et al., Journal of Virology 77 (3), 2003-2009 (2003)). At the
      end of 2007 the NMR structure of rabbit prion (124-228) was deposited into
      protein data bank (PDB entry 2FJ3). This paper studies the inhibition mechanism
      of rabbit prion at molecular structural level by molecular dynamics simulations.

PMID- 19583440
TI  - An insight to the dynamics of conserved water molecular triad in IMPDH II
      (human): recognition of cofactor and substrate to catalytic Arg 322.
AB  - Inosine 5' monophosphate dehydrogenase (IMPDH II) is a key enzyme involved in the
      de novo biosynthesis pathway of purine nucleotides and is also considered to be
      an excellent target for cancer inhibitor design. The conserve R 322 residue (in
      human) is thought to play some role in the recognition of inhibitor and cofactor
      through the catalytic D 364 and N 303. The 15 ns simulation and the water
      dynamics of the three different PDB structures (1B3O, 1NF7, and 1NFB) of human
      IMPDH by CHARMM force field have clearly indicated the involvement of three
      conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic
      residues (R 322, D 364, and N 303) to inhibitor and cofactor. Both the guanidine
      nitrogen atoms (NH1 and NH 2) of the R 322 have anchored the di- and mono
      nucleotide (cofactor and inhibitor) binding domains via the conserved W(C) and
      W(L) water molecules. Another conserved water molecule WM seems to bridge the two
      domains including the R 322 and also the W(C) and W(L) through seven centers H
      bonding coordination. The conserved water molecular triad (W(C)-W(M)-W(L)) in the
      protein complex may thought to play some important role in the recognition of
      inhibitor and cofactor to the protein through R 322 residue.

PMID- 19583442
TI  - Binding of TCA to the prion protein: mechanism, implication for therapy, and
      application as probe for complex formation of bio-macromolecules.
AB  - Tricyclic aromatic compounds (TCA) are promising candidates for treatment of
      transmissible spongiform encephalopathies. Direct binding to the cellular prion
      protein (PrP(C)) has been proposed as anti-prion active mechanism. We here show
      by means of NMR-spectroscopy that binding of TCA occurs with millimolar affinity
      to motifs consisting of two neighboring aromatic residues (Ar-Ar motif). It is
      independent of the secondary structure of this motif and of the side chain
      attached to the TCA and it is not specific to PrP(C). Because biologically
      inactive 9-aminoacridine (9-aa) binds with similar K(D) as anti-prion active
      quinacrine, direct interaction with PrP(C) as mechanism of action appears highly
      unlikely. However, binding of 9-aa to Ar-Ar-motifs in proteins can be used as
      reporter for biological macromolecule interactions, by measuring changes in T(1)
      NMR relaxation times of 9-aa.

PMID- 19583444
TI  - Computational model of the HIV-1 subtype A V3 loop: study on the conformational
      mobility for structure-based anti-AIDS drug design.
AB  - The V3 loop of the HIV-1gp120 glycoprotein presenting 35-residue-long, frequently
      glycosylated, highly variable, and disulfide bonded structure plays the central
      role in the virus biology and forms the principal target for neutralizing
      antibodies and the major viral determinant for co-receptor binding. Here we
      present the computer-aided studies on the 3D structure of the HIV-1 subtype A V3
      loop (SA-V3 loop) in which its structurally inflexible regions and individual
      amino acids were identified and the structure-function analysis of V3 aimed at
      the informational support for anti-AIDS drug researches was put into practice. To
      this end, the following successive steps were carried out: (i) using the methods
      of comparative modeling and simulated annealing, the ensemble of the low-energy
      structures was generated for the consensus amino acid sequence of the SA-V3 loop
      and its most probable conformation was defined basing on the general criteria
      widely adopted as a measure of the quality of protein structures in terms of
      their 3D folds and local geometry; (ii) the elements of secondary V3 structures
      in the built conformations were characterized and careful analysis of the
      corresponding data arising from experimental observations for the V3 loops in
      various HIV-1 strains was made; (iii) to reveal common structural motifs in the
      HIV-1 V3 loops regardless of their sequence variability and medium inconstancy,
      the simulated structures were collated with each other as well as with those of
      V3 deciphered by NMR spectroscopy and X-ray studies for diverse virus isolates in
      different environments; (iv) with the object of delving into the conformational
      features of the SA-V3 loop, molecular dynamics trajectory was computed from its
      static 3D structure followed by determining the structurally rigid V3 segments
      and comparing the findings obtained with the ones derived hereinbefore; and (v)
      to evaluate the masking effect that can occur due to interaction of the SA-V3
      loop with the two virtual molecules constructed previously by tools of
      computational modeling and named FKBP and CycA peptides, molecular docking of V3
      with these molecules was implemented and inter-atomic contacts appearing in the
      simulated complexes were analyzed to specify the V3 stretches keeping in touch
      with the ligands. As a matter of record, V3 segments 3-7, 15-20, and 28-32
      containing the highly conserved and biologically meaningful residues of gp120
      were shown to retain their 3D main chain shapes in all the cases of interest
      presenting the forward-looking targets for anti-AIDS drug researches. From the
      data on molecular docking, synthetic analogs of the CycA and FKBP peptides were
      suggested being suitable frameworks for making a reality of the V3-based anti-HIV
      1 drug projects.

PMID- 19583443
TI  - Ligand-based dual target drug design for H1N1: swine flu--a preliminary first
      study.
AB  - In March and April, 2009, an outbreak of H1N1 influenza in Mexico had led to
      hundreds of confirmed cases and the death toll had risen to 160. The worldwide
      spread of H1N1 has been attracting global attention and arising an overwhelming
      fear. So far, the vaccine and remedy has been in urgent need. In this study, a
      QSAR model and pharmacophore map of neuraminidase (NA) type 1 (N1) contained two
      hydrogen bond acceptor features, one hydrogen bond donor feature, and one
      positive ionizable feature. NCI database was employed in virtual screen by the N1
      pharmacophore map features. After screening, compounds were obtained and then
      docked into haemagglutinin type 1 (H1) to find out the candidate drugs for dual
      target of both N1 and H1. The candidate, NCI0353858, selected via virtual
      screening and docking, might be functional to this worldwide disease;
      consequently, further clinical investigations and scientific application are
      urgently demanded. We realize the proposed ligand does not have much validity
      without conducting a study on the stability of the protein-ligand complex by MD
      simulations and binding free energy, and such a study is underway and will be
      reported later in this journal. Nevertheless, the present study is clear,
      consistent and could give a rational explanation for the binding mode of the best
      selected ligand.

PMID- 19583446
TI  - Dissociation of protonated peptides containing adjacent arginines.
AB  - The dissociation of protonated peptides containing adjacent arginines has been
      studied by electrospray ionization-tandem mass spectrometry (ESI MS/MS) and
      theoretical calculations. The experimental results show that singly protonated
      peptides cleave at the Arg-Arg amide bond and generate the y(1) ion when adjacent
      arginines are the C-terminal residues. The major cleavage occurs at the C
      terminal amide bond and produces the b(n-1) ion when adjacent arginines are not
      the C-terminal residues. The diketopiperazine and oxazolone fragmentation
      pathways of protonated NRR (Asn-Arg-Arg) have been investigated at the B3LYP/6
      31G(d) and B3LYP/6-31++G(d,p) levels of theory. The geometries and energies of
      transition state species and hydrogen-bonding interaction are also discussed.

PMID- 19583445
TI  - Construction and assessment of reaction models of class I EPSP synthase:
      molecular docking and density functional theoretical calculations.
AB  - The high frequency of contamination by herbicides suggests the need for more
      active and selective herbicides. Glyphosate is the active component of one of the
      top-selling herbicides, which is also a potent EPSP synthase inhibitor. That is a
      key enzyme in the shikimic acid pathway, which is found only in plants and some
      microorganisms. Thus, EPSP synthase is regarded as a prime target for herbicides.
      In this line, molecular modeling studies using molecular dynamics simulations and
      DFT techniques were performed to understand the interaction of glyphosate and its
      analogs with the wild type enzyme and Gly96Ala mutant EPSP synthase. In addition,
      we investigated the reaction mechanism of the natural substrate. Our findings
      indicate some key points to the design of new selective glyphosate derivates.

PMID- 19583447
TI  - RecA-mediated cleavage of lambda cI repressor accepts repressor dimers: probable
      role of prolyl cis-trans isomerization and catalytic involvement of H163, K177,
      and K232 of RecA.
AB  - The lambda cI repressor is found to be cleaved in the presence of activated RecA
      in its DNA-bound dimeric form at a rate similar to that in the absence of
      operator DNA in contrast to previous studies inferring repressor monomer as a
      preferred substrate. Though activated RecA does not possess any measurable
      isomerase activity against a standard peptide substrate, prolyl isomerase
      inhibitors cyclosporin A and rapamycin do inhibit RecA-mediated cleavage.
      Histidine and lysine to a smaller extent, are shown to cleave cI repressor in a
      non-enzymatic fashion whereas arginine and glutamate do not. When activated RecA
      filament is covalently modified by using an excess of diethyl pyrocarbonate or
      maleic anhydride, RecA-mediated cleavage of cI repressor is inhibited. Combining
      our chemical modification data with model building and earlier mutagenesis data,
      it is argued that H163, K177, and K232 in RecA are crucial residues involved in
      cI repressor cleavage by combining with the catalytic Ser149 and K192 in the
      repressor. It is suggested by model building that subunits n, n+4, and n+5 in the
      RecA filament contribute one loop each for holding the C-terminal domain of the
      repressor during cleavage within the RecA helical groove, explaining why its ADP
      form is inactive and its ATP-form is active regarding repressor cleavage.

PMID- 19583448
TI  - Kinetic effects on signal normalization in oligonucleotide microchips with
      labeled immobilized probes.
AB  - Among various factors affecting operation of oligonucleotide microchips, the
      variations in concentration and in homogeneous distribution of immobilized probes
      over the cells are one of the most important. The labeling of immobilized probes
      ensures the complete current monitoring on the probe distribution and is reliable
      and convenient. Using hydrogel-based oligonucleotide microchips, the
      applicability of Cy3-labeled immobilized probes for quality control and signal
      normalization after hybridization with Cy5-labeled target DNA was investigated.
      This study showed that proper signal normalization should be different in
      thermodynamic conditions and in transient regime with hybridization far from
      saturation. This kinetic effect holds for both hydrogel-based and surface
      oligonucleotide microchips. Besides proving basic features, the technique was
      assessed on a sampling batch of 50 microchips developed for identifying mutations
      responsible for rifampicin and isoniazid resistance of Mycobacterium
      tuberculosis.

PMID- 19583449
TI  - Viral myocarditis: diagnosis, aetiology and management.
AB  - Myocarditis is an inflammatory disease of the cardiac muscle caused by myocardial
      infiltration of immunocompetent cells following any kind of cardiac injury.
      Classic myocarditis mainly occurs as a result of the host's immune response
      against organisms that cause common infectious illnesses, as a manifestation of
      hypersensitivity or as a toxic reaction to drug therapy. Chronic inflammatory
      events may survive successful clearance of initial cardiotoxic agents, be
      triggered or amplified by autoimmunological processes, or develop in the context
      of systemic diseases. If the underlying infectious or immune-mediated causes of
      the disease are carefully defined by clinical and biopsy-based tools, specific
      immunosuppressive and antiviral treatment options may improve the prognosis of
      patients with acute and chronic disease.

PMID- 19583450
TI  - Idiopathic membranous nephropathy: management strategies.
AB  - Treatment of idiopathic membranous nephropathy is based on a 'symptomatic'
      therapy that includes ACE inhibitors or angiotensin II receptor antagonists, and
      on an 'aetiological' therapy aimed at modulating underlying immunological
      mechanisms. The role of the latter is still debated given the usually indolent
      course of disease; furthermore, traditional immunosuppressants would not have an
      impact on patient and renal survival according to a systematic review of
      literature. However, up to 40% of untreated patients eventually develop end-stage
      renal disease and remission of nephrotic syndrome protects patients from related
      life-threatening complications and is the strongest positive prognostic factor
      for long-term kidney function. Therefore, immunosuppressive therapy seems to be
      rational in high-risk patients with nephrotic syndrome or deteriorating renal
      function. This article outlines a possible role for each 'aetiological' therapy
      on the basis of available evidence in order to provide some practical
      recommendations. The first-line therapy is based on a 6-month regimen of
      alternating corticosteroids and an alkylating agent ('Ponticelli' regimen),
      whereas oral ciclosporin and intramuscular corticotrophin (adrenocorticotrophic
      hormone) are alternatives that provide comparable results in terms of remission
      of proteinuria, with a different adverse effect profile. New drugs are emerging
      as potential treatments, such as mycophenolate mofetil, tacrolimus, intravenous
      immunoglobulins and rituximab. Specific settings, such as chronic renal failure
      or elderly age, require a careful balance between benefits and toxicity of
      immunosuppression. The tailor-made use of this repertoire of drugs can provide a
      tool to achieve remission of proteinuria and modify the natural course of
      idiopathic membranous nephropathy.

PMID- 19583451
TI  - Varenicline: a novel pharmacotherapy for smoking cessation.
AB  - Varenicline is an orally administered small molecule with partial agonist
      activity at the alpha4beta2 nicotinic acetylcholine receptor. Varenicline was
      approved by both the US FDA and the European Medicines Agency of the EU in 2006
      as an aid to smoking cessation. Subsequently, varenicline has been approved in
      over 80 other countries. Varenicline is almost entirely absorbed following oral
      administration, and absorption is unaffected by food, smoking or the time of day.
      Varenicline undergoes only minimal metabolism and approximately 90% of the drug
      is excreted in the urine unchanged. Varenicline has a mean elimination half-life
      after repeated administration of approximately 24 hours in smokers. The area
      under the plasma concentration-time curve is increased in patients with moderate
      or severe renal failure. No clinically relevant varenicline-drug interactions
      have been identified. In two identical, randomized, double-blind, phase III
      clinical trials in healthy, motivated-to-quit, mainly Caucasian smokers aged 18
      75 years in the US, 12 weeks of treatment with varenicline 1 mg twice daily was
      associated with significantly higher abstinence rates over weeks 9-12 than
      sustained-release bupropion 150 mg twice daily or placebo. In a separate phase
      III trial, an additional 12 weeks of treatment in smokers achieving abstinence in
      the first 12 weeks was associated with greater abstinence through to week 52 than
      placebo treatment. Varenicline treatment was also associated with significantly
      higher rates of abstinence than placebo treatment in randomized, double-blind,
      clinical trials in smokers in China, Japan, Korea, Singapore, Taiwan and
      Thailand. In a randomized, open-label, multi-national, phase III trial,
      varenicline treatment was associated with a significantly higher rate of
      abstinence than transdermal nicotine-replacement therapy. In these trials,
      varenicline treatment was associated with lower urge to smoke and satisfaction
      from smoking in relapsers than placebo or active comparators. In the two US phase
      III trials, 12 weeks of treatment with varenicline 1 mg twice daily had an
      acceptable safety and tolerability profile. Nausea and abnormal dreams were the
      most common adverse events that occurred in more varenicline than placebo
      recipients. The incidence and prevalence of nausea were greatest in weeks 1 and 2
      of treatment, and declined thereafter. The prevalence of early adverse effects
      can be reduced by individual dose titration. Adverse events associated with
      varenicline therapy have been reported in post-marketing surveillance, including
      neuropsychiatric events such as depressed mood, agitation, changes in behaviour,
      suicidal ideation and suicide. Currently, it is unclear whether the association
      of varenicline therapy with these adverse events is causal, coincidental or
      related to smoking cessation. Given the greater efficacy of varenicline compared
      with other pharmacotherapies, and the high risk of morbidity and mortality
      associated with continued smoking, varenicline is a valuable pharmacological aid
      to smoking cessation.

PMID- 19583453
TI  - Outcome of antimicrobial therapy in documented biofilm-associated infections: a
      review of the available clinical evidence.
AB  - Numerous laboratory findings indicate that microbial biofilms may be encountered
      in several types of human infections, affecting the activity of antimicrobial
      agents. We evaluated the clinical evidence regarding the effectiveness of
      antimicrobial therapy for infections documented to be biofilm-associated, by
      performing a review of 15 relevant studies, excluding dental and eye infections.
      In a clinical trial, a significant difference was noted in the effectiveness of
      antibacterial agents used for catheter-related urinary tract infections in which
      substantial bacterial adherence on uroepithelial cells was observed. In case
      series and case reports, 28 patients with biofilm-associated infections
      documented by electron microscopy scanning were identified. Infection sites
      included ear, urinary tract, CNS, bloodstream and foreign body implantation site.
      Pseudomonas and Staphylococcus spp. were the predominant microorganisms among the
      bacterial or fungal causative pathogens. In 24 cases, infections related to the
      presence of foreign bodies. Treatment failure or recurrence was noted in all
      eight patients in whom targeted antimicrobial therapy was instituted before
      foreign body removal. Foreign body removal coupled with antimicrobial therapy was
      effective in all ten relevant cases. In four cases of native tissue urinary tract
      infections, the outcome of the initial antimicrobial therapy was poor. The
      limited available relevant clinical evidence indicates that conventional
      antimicrobial therapy alone is not adequately effective against documented
      biofilm-associated infections. Although some regimens might be more appropriate
      in this setting, further research on novel therapeutic strategies is needed to
      improve the outcome of patients with biofilm-associated infections.

PMID- 19583452
TI  - The role of oral beclometasone dipropionate in the treatment of gastrointestinal
      Graft-versus-Host Disease.
AB  - Graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation
      causes significant morbidity and mortality. An important site of GVHD is the
      gastrointestinal (GI) tract because development of acute GI GVHD is prognostic of
      overall survival. The standard of care to treat acute GI GVHD is systemic
      corticosteroids and immunosuppressants; however, the use of these therapies can
      cause life-threatening opportunistic infections. To limit the adverse effects of
      systemic immunosuppression, the topically active corticosteroid beclometasone
      dipropionate has been investigated in case studies and in randomized placebo
      controlled trials for the treatment of acute GI GVHD. In this review, we appraise
      these studies with beclometasone dipropionate, and discuss future randomized
      studies to clarify the role of beclometasone dipropionate for the treatment and
      prevention of acute GVHD. At present, more data are required before the addition
      of beclometasone dipropionate to systemic corticosteroids for the treatment of
      acute GVHD can be considered the standard of care.

PMID- 19583454
TI  - Torasemide prolonged release.
AB  - Torasemide prolonged release (PR), a high-ceiling diuretic, inhibits renal
      tubular reabsorption of sodium and chloride in the thick ascending limb of the
      loop of Henle. Relative to the immediate-release (IR) formulation, the PR
      formulation of torasemide was associated with similar systemic exposure, but
      significantly slower rates of absorption and lower fluctuations in plasma
      concentrations, and provided higher natriuretic efficiency and more constant
      diuresis. The antihypertensive efficacy of once-daily torasemide PR 5-10 mg was
      noninferior to that of once-daily torasemide IR 5-10 mg with regard to the change
      from baseline in sitting diastolic BP (primary endpoint) in a 12-week,
      randomized, double-blind trial in patients with mild to moderate hypertension.
      Sitting systolic BP (SBP) decreased from baseline to a similar extent in the
      overall population of the treatment groups at week 12. However, daytime SBP
      decreased to a significantly greater extent with torasemide PR than IR in a
      subgroup of patients who underwent ambulatory 24-hour BP monitoring. Patients
      receiving torasemide PR were more likely to achieve adequate control of BP at
      weeks 8 and 12 than those receiving torasemide IR. The PR formulation of
      torasemide was well tolerated in the clinical trial, with a tolerability profile
      that was similar to that with the IR formulation.

PMID- 19583455
TI  - Rabeprazole: a review of its use in the management of gastric acid-related
      diseases in adults.
AB  - Rabeprazole (Aciphex, Alfence, Pariet) is a proton pump inhibitor (PPI) used for
      the treatment of adults with conditions requiring a reduction of gastric acid
      secretion such as erosive or ulcerative gastro-oesophageal reflux disease (GORD),
      non-erosive reflux disease (NERD), duodenal and gastric ulcers, and pathological
      hypersecretory conditions including Zollinger-Ellison syndrome (ZES). It is also
      used as part of combination therapy for the eradication of Helicobacter pylori, a
      pathogen frequently implicated in the development of gastric and duodenal ulcers.
      Rabeprazole has a well established efficacy and safety profile in the treatment
      of gastric acid-related diseases. Rabeprazole is a useful, well tolerated and
      cost-effective option for the treatment of GORD, NERD, peptic ulcer and other
      gastric acid-related diseases (including ZES), and provides an appropriate
      alternative to other currently available PPIs, with the added benefits of having
      a consistent efficacy profile and low drug interaction potential due to its
      predominantly nonenzymatic metabolism.

PMID- 19583458
TI  - [Detection situation of an adhesion factor in diarrheagenic Escherichia coli].
AB  - Diarrhea caused by the Escherichia coli with held adhesion came to attention. We
      performed an adhesion-related gene and relation of diarrhea. Subjects were 77
      outpatients with diarrhea from June 2003 to December 2005. A total of 102 E. coli
      strains randomly isolated from stool specimens. All the toxigenic examinations
      were negative, and there were not the relations. Adhesion-related gene were 10
      strains found. As for the contents, astA was 5 strains, 2 strains of aggR, 2
      strains of eaeA, 1 strain of eaeA plus astA. Of these, we were able to classify 5
      strains in serological typing, but remain 5 strains did not typing. Only one
      strain of O157 was VT positive. There is not it with causative E. coli of
      diarrhea even if serological typing is negative. Therefore it was thought that an
      adhesion-related gene test was important.

PMID- 19583457
TI  - [Evaluation of rapid antimicrobial susceptibility test for Staphylococcus aureus
      by chemiluminescent assay and its application for screening of beta-lactam
      antibiotic induced vancomycin-resistant MRSA].
AB  - Minimum inhibitory concentrations (MICs) of vancomycin (VCM) and teicoplanin
      (TEIC) were measured using a novel susceptibility test based on the
      chemiluminescence assay method (CA) (Rapid-Lumi Eiken; Eiken Chemicals, Tokyo,
      Japan) against 84 strains of Staphylococcus aureus, consisting of 82 strains of
      methicillin-resistant S. aureus (MRSA) from clinical isolated, S. aureus Mu3
      involving beta-lactam antibiotic induced vancomycin (VCM) resistant MRSA (BIVR)
      and methicillin-susceptible S. aureus ATCC 29213. The results were in good
      accordance with the values determined by Clinical and Laboratory Standards
      Institute (CLSI): i.e., 100% (84/84) of consistency for VCM and 95% (80/84) for
      TEIC, respectively. In addition, BIVR strains were properly estimated from the
      results of the CA method and using the BIVR detection method with Mu3 agar (Mu3
      Agar method), even though the incubation times was very short (2-4 h). In
      conclusion, it was found that the new method is reliable and rapid to detect BIVR
      strains in clinical laboratories.

PMID- 19583456
TI  - [Epidemiological search for vancomycin-resistant enterococci in mainland of the
      Ryukyus].
AB  - During the period from January through December 2007, a total of 1,814 stool
      specimens from the inpatients of nine regional hospitals in mainland of the
      Ryukyus, were tested to identify vancomycin-resistant enterococci (VRE). All the
      stool specimens were primarily cultured onto the VRE selective agar plates, and a
      total of 195 specimens yielded positive enterococcal growth. Of 195 isolates, VRE
      screening agar tests identified 106 phenotypic VRE isolates, consisting 24
      isolates of Enterococcus casseliflavus, 12 of E. faecalis, 4 of E. faecium, and
      66 of E. gallinarum. Then, the 106 VRE isolates were tested for vanA and vanB
      genes by polymerase chain reaction, the results indicating none of the isolates
      were positive for vanA or vanB genes. With these results, it can be concluded
      that, at present, mainland of the Ryukyus is VRE-free area, and it is necessary
      to continue careful search for incoming and spreading of VRE positive for vanA
      and vanB genes in Okinawa.

PMID- 19583459
TI  - Reliability of using urinary and blood trichloroacetic acid as a biomarker of
      exposure to chlorinated drinking water disinfection byproducts.
AB  - This study was designed to analyse the reliability of using urinary and blood
      trichloroacetic acid (TCAA) as a biomarker of exposure. A total of 46 healthy
      women consumed supplied TCAA-containing tap water for 15 days and provided urine
      and blood samples for TCAA measurements. The findings revealed that the
      reliability of measurements was excellent by using measures of TCAA ingestion,
      blood concentration and urinary excretion (intraclass correlation coefficients
      (ICC) > 0.75, p < 0.001). Volume of tap water consumption (ICC = 0.69) and
      creatinine-adjusted urinary concentration (ICC = 0.72) were less reliable. This
      indicated that the intraindividual variability was small and the interindividual
      reliability was high by using these measures in this cohort study. Laboratory
      variability did not significantly contribute to total variance (ICC > 0.95, p <
      0.001). Other possible sources of variation such as bathing, showering,
      dishwashing and physical activities were unlikely to contribute significantly to
      total variance. For sampling strategies, 1-day blood sampling and 2-day urine
      sampling are sufficient to achieve reliability for an epidemiological study if a
      quasi-steady-state TCAA level in the body is reached. The results suggest that
      TCAA ingestion, TCAA loading in blood and urinary TCAA excretion are reliable
      measures for use as biomarkers in epidemiological studies.

PMID- 19583460
TI  - In vivo lymphatic targeting of methylene blue with microemulsion and multiple
      microemulsion.
AB  - Three formulations including methylene blue solution (MB-S), MB water-in-oil
      microemulsion (MB-ME), and MB multiple microemulsion (MB-MME) were prepared with
      the aim to evaluate whether the three formulations can carry MB target to
      regional lymph nodes and show lymphatic tropism after subcutaneous
      administration. The pseudo-ternary phase diagrams were also studied. The
      morphology of MB-ME and MB-MME was examined by transmission electron microscopy
      to characterize the microstructure. The particle size and viscosity were also
      measured. MB concentrations in plasma, lymph nodes, and limb soles were
      quantitatively analyzed using HPLC. Results show that MME can target MB to
      regional lymph nodes, and can be employed as a potential lymph tracer in sentinel
      lymph node biopsy.

PMID- 19583461
TI  - The role of mechanical loading in ligament tissue engineering.
AB  - Tissue-engineered ligaments have received growing interest as a promising
      alternative for ligament reconstruction when traditional transplants are
      unavailable or fail. Mechanical stimulation was recently identified as a critical
      component in engineering load-bearing tissues. It is well established that living
      tissue responds to altered loads through endogenous changes in cellular behavior,
      tissue organization, and bulk mechanical properties. Without the appropriate
      biomechanical cues, new tissue formation lacks the necessary collagenous
      organization and alignment for sufficient load-bearing capacity. Therefore,
      tissue engineers utilize mechanical conditioning to guide tissue remodeling and
      improve the performance of ligament grafts. This review provides a comparative
      analysis of the response of ligament and tendon fibroblasts to mechanical loading
      in current bioreactor studies. The differential effect of mechanical stimulation
      on cellular processes such as protease production, matrix protein synthesis, and
      cell proliferation is examined in the context of tissue engineering design.

PMID- 19583462
TI  - The impact of biomechanics in tissue engineering and regenerative medicine.
AB  - Biomechanical factors profoundly influence the processes of tissue growth,
      development, maintenance, degeneration, and repair. Regenerative strategies to
      restore damaged or diseased tissues in vivo and create living tissue replacements
      in vitro have recently begun to harness advances in understanding of how cells
      and tissues sense and adapt to their mechanical environment. It is clear that
      biomechanical considerations will be fundamental to the successful development of
      clinical therapies based on principles of tissue engineering and regenerative
      medicine for a broad range of musculoskeletal, cardiovascular, craniofacial,
      skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key
      to producing regenerated tissues with high strength and endurance. However, many
      challenges remain, particularly for tissues that function within complex and
      demanding mechanical environments in vivo. This paper reviews the present role
      and potential impact of experimental and computational biomechanics in
      engineering functional tissues using several illustrative examples of past
      successes and future grand challenges.

PMID- 19583463
TI  - Evidence for early morphological decomposition in visual word recognition.
AB  - We employ a single-trial correlational MEG analysis technique to investigate
      early processing in the visual recognition of morphologically complex words.
      Three classes of affixed words were presented in a lexical decision task: free
      stems (e.g., taxable), bound roots (e.g., tolerable), and unique root words
      (e.g., vulnerable, the root of which does not appear elsewhere). Analysis was
      focused on brain responses within 100-200 msec poststimulus onset in the
      previously identified letter string and visual word-form areas. MEG data were
      analyzed using cortically constrained minimum-norm estimation. Correlations were
      computed between activity at functionally defined ROIs and continuous measures of
      the words' morphological properties. ROIs were identified across subjects on a
      reference brain and then morphed back onto each individual subject's brain (n =
      9). We find evidence of decomposition for both free stems and bound roots at the
      M170 stage in processing. The M170 response is shown to be sensitive to
      morphological properties such as affix frequency and the conditional probability
      of encountering each word given its stem. These morphological properties are
      contrasted with orthographic form features (letter string frequency, transition
      probability from one string to the next), which exert effects on earlier stages
      in processing ( approximately 130 msec). We find that effects of decomposition at
      the M170 can, in fact, be attributed to morphological properties of complex
      words, rather than to purely orthographic and form-related properties. Our data
      support a model of word recognition in which decomposition is attempted, and
      possibly utilized, for complex words containing bound roots as well as free word
      stems.

PMID- 19583464
TI  - Effect of attention on early cortical processes associated with the sound-induced
      extra flash illusion.
AB  - When a single flash of light is presented interposed between two brief auditory
      stimuli separated by 60-100 msec, subjects typically report perceiving two
      flashes [Shams, L., Kamitani, Y., & Shimojo, S. Visual illusion induced by sound.
      Brain Research, Cognitive Brain Research, 14, 147-152, 2002; Shams, L., Kamitani,
      Y., & Shimojo, S. Illusions. What you see is what you hear. Nature, 408, 788,
      2000]. Using ERP recordings, we previously found that perception of the illusory
      extra flash was accompanied by a rapid dynamic interplay between auditory and
      visual cortical areas that was triggered by the second sound [Mishra, J.,
      Martinez, A., Sejnowski, T. J., & Hillyard, S. A. Early cross-modal interactions
      in auditory and visual cortex underlie a sound-induced visual illusion. Journal
      of Neuroscience, 27, 4120-4131, 2007]. In the current study, we investigated the
      effect of attention on the ERP components associated with the illusory extra
      flash in 15 individuals who perceived this cross-modal illusion frequently. All
      early ERP components in the cross-modal difference wave associated with the extra
      flash illusion were significantly enhanced by selective spatial attention. The
      earliest attention-related modulation was an amplitude increase of the positive
      going PD110/PD120 component, which was previously shown to be correlated with an
      individual's propensity to perceive the illusory second flash [Mishra, J.,
      Martinez, A., Sejnowski, T. J., & Hillyard, S. A. Early cross-modal interactions
      in auditory and visual cortex underlie a sound-induced visual illusion. Journal
      of Neuroscience, 27, 4120-4131, 2007]. The polarity of the early PD110/PD120
      component did not differ as a function of the visual field (upper vs. lower) of
      stimulus presentation. This, along with the source localization of the component,
      suggested that its principal generator lies in extrastriate visual cortex. These
      results indicate that neural processes previously shown to be associated with the
      extra flash illusion can be modulated by attention, and thus are not the result
      of a wholly automatic cross-modal integration process.

PMID- 19583465
TI  - Temporal integration in visual word recognition.
AB  - When two displays are presented in close temporal succession at the same
      location, how does the brain assign them to one versus two conscious percepts? We
      investigate this issue using a novel reading paradigm in which the odd and even
      letters of a string are presented alternatively at a variable rate. The results
      reveal a window of temporal integration during reading, with a nonlinear boundary
      around approximately 80 msec of presentation duration. Below this limit, the
      oscillating stimulus is easily fused into a single percept, with all
      characteristics of normal reading. Above this limit, reading times are severely
      slowed and suffer from a word-length effect. ERPs indicate that, even at the
      fastest frequency, the oscillating stimulus elicits synchronous oscillations in
      posterior visual cortices, while late ERP components sensitive to lexical status
      vanish beyond the fusion threshold. Thus, the fusion/segregation dilemma is not
      resolved by retinal or subcortical filtering, but at cortical level by at most
      300 msec. The results argue against theories of visual word recognition and
      letter binding that rely on temporal synchrony or other fine temporal codes.

PMID- 19583466
TI  - Human visual system automatically encodes sequential regularities of discrete
      events.
AB  - For our adaptive behavior in a dynamically changing environment, an essential
      task of the brain is to automatically encode sequential regularities inherent in
      the environment into a memory representation. Recent studies in neuroscience have
      suggested that sequential regularities embedded in discrete sensory events are
      automatically encoded into a memory representation at the level of the sensory
      system. This notion is largely supported by evidence from investigations using
      auditory mismatch negativity (auditory MMN), an event-related brain potential
      (ERP) correlate of an automatic memory-mismatch process in the auditory sensory
      system. However, it is still largely unclear whether or not this notion can be
      generalized to other sensory modalities. The purpose of the present study was to
      investigate the contribution of the visual sensory system to the automatic
      encoding of sequential regularities using visual mismatch negativity (visual
      MMN), an ERP correlate of an automatic memory-mismatch process in the visual
      sensory system. To this end, we conducted a sequential analysis of visual MMN in
      an oddball sequence consisting of infrequent deviant and frequent standard
      stimuli, and tested whether the underlying memory representation of visual MMN
      generation contains only a sensory memory trace of standard stimuli (trace
      mismatch hypothesis) or whether it also contains sequential regularities
      extracted from the repetitive standard sequence (regularity-violation
      hypothesis). The results showed that visual MMN was elicited by first deviant
      (deviant stimuli following at least one standard stimulus), second deviant
      (deviant stimuli immediately following first deviant), and first standard
      (standard stimuli immediately following first deviant), but not by second
      standard (standard stimuli immediately following first standard). These results
      are consistent with the regularity-violation hypothesis, suggesting that the
      visual sensory system automatically encodes sequential regularities. In
      combination with a wide range of auditory MMN studies, the present study
      highlights the critical role of sensory systems in automatically encoding
      sequential regularities when modeling the world.

PMID- 19583468
TI  - New names for known things: on the association of novel word forms with existing
      semantic information.
AB  - The plasticity of the adult memory network for integrating novel word forms
      (lexemes) was investigated with whole-head magnetoencephalography (MEG). We
      showed that spoken word forms of an (artificial) foreign language are integrated
      rapidly and successfully into existing lexical and conceptual memory networks.
      The new lexemes were learned in an untutored way, by pairing them frequently with
      one particular object (and thus meaning), and infrequently with 10 other objects
      (learned set). Other novel word forms were encountered just as often, but paired
      with many different objects (nonlearned set). Their impact on semantic memory was
      assessed with cross-modal priming, with novel word forms as primes and object
      pictures as targets. The MEG counterpart of the N400 (N400m) served as an
      indicator of a semantic (mis)match between words and pictures. Prior to learning,
      all novel words induced a pronounced N400m mismatch effect to the pictures. This
      component was strongly reduced after training for the learned novel lexemes only,
      and now closely resembled the brain's response to semantically related native
      language words. This result cannot be explained by mere stimulus repetition or
      stimulus-stimulus association. Thus, learned novel words rapidly gained access to
      existing conceptual representations, as effectively as related native-language
      words. This association of novel lexemes and conceptual information happened fast
      and almost without effort. Neural networks mediating these integration processes
      were found within left temporal lobe, an area typically described as one of the
      main generators of the N400 response.

PMID- 19583467
TI  - Prestimulus subsequent memory effects for auditory and visual events.
AB  - It has been assumed that the effective encoding of information into memory
      primarily depends on neural activity elicited when an event is initially
      encountered. Recently, it has been shown that memory formation also relies on
      neural activity just before an event. The precise role of such activity in memory
      is currently unknown. Here, we address whether prestimulus activity affects the
      encoding of auditory and visual events, is set up on a trial-by-trial basis, and
      varies as a function of the type of recognition judgment an item later receives.
      Electrical brain activity was recorded from the scalps of 24 healthy young adults
      while they made semantic judgments on randomly intermixed series of visual and
      auditory words. Each word was preceded by a cue signaling the modality of the
      upcoming word. Auditory words were preceded by auditory cues and visual words by
      visual cues. A recognition memory test with remember/know judgments followed
      after a delay of about 45 min. As observed previously, a negative-going,
      frontally distributed modulation just before visual word onset predicted later
      recollection of the word. Crucially, the same effect was found for auditory words
      and observed on stay as well as switch trials. These findings emphasize the
      flexibility and general role of prestimulus activity in memory formation, and
      support a functional interpretation of the activity in terms of semantic
      preparation. At least with an unpredictable trial sequence, the activity is set
      up anew on each trial.

PMID- 19583469
TI  - Coercion and compositionality.
AB  - Research in psycholinguistics and in the cognitive neuroscience of language has
      suggested that semantic and syntactic processing are associated with different
      neurophysiologic correlates, such as the N400 and the P600 in the ERPs. However,
      only a handful of studies have investigated the neural basis of the syntax
      semantics interface, and even fewer experiments have dealt with the cases in
      which semantic composition can proceed independently of the syntax. Here we
      looked into one such case-complement coercion--using ERPs. We compared sentences
      such as, "The journalist wrote the article" with "The journalist began the
      article." The second sentence seems to involve a silent semantic element, which
      is expressed in the first sentence by the head of the verb phrase (VP) "wrote the
      article." The second type of construction may therefore require the reader to
      infer or recover from memory a richer event sense of the VP "began the article,"
      such as began writing the article, and to integrate that into a semantic
      representation of the sentence. This operation is referred to as "complement
      coercion." Consistently with earlier reading time, eye tracking, and MEG studies,
      we found traces of such additional computations in the ERPs: Coercion gives rise
      to a long-lasting negative shift, which differs at least in duration from a
      standard N400 effect. Issues regarding the nature of the computation involved are
      discussed in the light of a neurocognitive model of language processing and a
      formal semantic analysis of coercion.

PMID- 19583470
TI  - Lexical competition in nonnative speech comprehension.
AB  - Electrophysiological studies consistently find N400 effects of semantic
      incongruity in nonnative (L2) language comprehension. These N400 effects are
      often delayed compared with native (L1) comprehension, suggesting that semantic
      integration in one's second language occurs later than in one's first language.
      In this study, we investigated whether such a delay could be attributed to (1)
      intralingual lexical competition and/or (2) interlingual lexical competition. We
      recorded EEG from Dutch-English bilinguals who listened to English (L2) sentences
      in which the sentence-final word was (a) semantically fitting and (b)
      semantically incongruent or semantically incongruent but initially congruent due
      to sharing initial phonemes with (c) the most probable sentence completion within
      the L2 or (d) the L1 translation equivalent of the most probable sentence
      completion. We found an N400 effect in each of the semantically incongruent
      conditions. This N400 effect was significantly delayed to L2 words but not to L1
      translation equivalents that were initially congruent with the sentence context.
      Taken together, these findings firstly demonstrate that semantic integration in
      nonnative listening can start based on word initial phonemes (i.e., before a
      single lexical candidate could have been selected based on the input) and
      secondly suggest that spuriously elicited L1 lexical candidates are not available
      for semantic integration in L2 speech comprehension.

PMID- 19583471
TI  - The function of words: distinct neural correlates for words denoting differently
      manipulable objects.
AB  - Recent research indicates that language processing relies on brain areas
      dedicated to perception and action. For example, processing words denoting
      manipulable objects has been shown to activate a fronto-parietal network involved
      in actual tool use. This is suggested to reflect the knowledge the subject has
      about how objects are moved and used. However, information about how to use an
      object may be much more central to the conceptual representation of an object
      than information about how to move an object. Therefore, there may be much more
      fine-grained distinctions between objects on the neural level, especially related
      to the usability of manipulable objects. In the current study, we investigated
      whether a distinction can be made between words denoting (1) objects that can be
      picked up to move (e.g., volumetrically manipulable objects: bookend, clock) and
      (2) objects that must be picked up to use (e.g., functionally manipulable
      objects: cup, pen). The results show that functionally manipulable words elicit
      greater levels of activation in the fronto-parietal sensorimotor areas than
      volumetrically manipulable words. This suggests that indeed a distinction can be
      made between different types of manipulable objects. Specifically, how an object
      is used functionally rather than whether an object can be displaced with the hand
      is reflected in semantic representations in the brain.

PMID- 19583472
TI  - The evocative power of sounds: conceptual priming between words and nonverbal
      sounds.
AB  - Two experiments were conducted to examine the conceptual relation between words
      and nonmeaningful sounds. In order to reduce the role of linguistic mediation,
      sounds were recorded in such a way that it was highly unlikely to identify the
      source that produced them. Related and unrelated sound-word pairs were presented
      in Experiment 1 and the order of presentation was reversed in Experiment 2 (word
      sound). Results showed that, in both experiments, participants were sensitive to
      the conceptual relation between the two items. They were able to correctly
      categorize items as related or unrelated with good accuracy. Moreover, a
      relatedness effect developed in the event-related brain potentials between 250
      and 600 msec, although with a slightly different scalp topography for word and
      sound targets. Results are discussed in terms of similar conceptual processing
      networks and we propose a tentative model of the semiotics of sounds.

PMID- 19583474
TI  - Visual anticipatory information modulates multisensory interactions of artificial
      audiovisual stimuli.
AB  - The neural activity of speech sound processing (the N1 component of the auditory
      ERP) can be suppressed if a speech sound is accompanied by concordant lip
      movements. Here we demonstrate that this audiovisual interaction is neither
      speech specific nor linked to humanlike actions but can be observed with
      artificial stimuli if their timing is made predictable. In Experiment 1, a pure
      tone synchronized with a deformation of a rectangle induced a smaller auditory N1
      than auditory-only presentations if the temporal occurrence of this audiovisual
      event was made predictable by two moving disks that touched the rectangle. Local
      autoregressive average source estimation indicated that this audiovisual
      interaction may be related to integrative processing in auditory areas. When the
      moving disks did not precede the audiovisual stimulus--making the onset
      unpredictable--there was no N1 reduction. In Experiment 2, the predictability of
      the leading visual signal was manipulated by introducing a temporal asynchrony
      between the audiovisual event and the collision of moving disks. Audiovisual
      events occurred either at the moment, before (too "early"), or after (too "late")
      the disks collided on the rectangle. When asynchronies varied from trial to trial
      -rendering the moving disks unreliable temporal predictors of the audiovisual
      event--the N1 reduction was abolished. These results demonstrate that the N1
      suppression is induced by visual information that both precedes and reliably
      predicts audiovisual onset, without a necessary link to human action-related
      neural mechanisms.

PMID- 19583473
TI  - Responding with restraint: what are the neurocognitive mechanisms?
AB  - An important aspect of cognitive control is the ability to respond with
      restraint. Here, we modeled this experimentally by measuring the degree of
      response slowing that occurs when people respond to an imperative stimulus in a
      context where they might suddenly need to stop the initiated response compared
      with a context in which they do not need to stop. We refer to the RT slowing that
      occurs as the "response delay effect." We conjectured that this response delay
      effect could relate to one or more neurocognitive mechanism(s): partial response
      suppression (i.e., "active braking"), prolonged decision time, and slower
      response facilitation. These accounts make different predictions about motor
      system excitability and brain activation. To test which neurocognitive mechanisms
      underlie the response delay effect, we performed two studies with TMS and we
      reanalyzed fMRI data. The results suggest that the response delay effect is at
      least partly explained by active braking, possibly involving a mechanism that is
      similar to that used to stop responses completely. These results further our
      understanding of how people respond with restraint by pointing to proactive
      recruitment of a neurocognitive mechanism heretofore associated with outright
      stopping.

PMID- 19583475
TI  - Ketamine modulates theta and gamma oscillations.
AB  - Ketamine, an N-methyl-D-aspartate (NMDA) receptor glutamatergic antagonist, has
      been studied as a model of schizophrenia when applied in subanesthetic doses. In
      EEG studies, ketamine affects sensory gating and alters the oscillatory
      characteristics of neuronal signals in a complex manner. We investigated the
      effects of ketamine on in vivo recordings from the CA3 region of mouse
      hippocampus referenced to the ipsilateral frontal sinus using a paired-click
      auditory gating paradigm. One issue of particular interest was elucidating the
      effect of ketamine on background network activity, poststimulus evoked and
      induced activity. We find that ketamine attenuates the theta frequency band in
      both background activity and in poststimulus evoked activity. Ketamine also
      disrupts a late, poststimulus theta power reduction seen in control recordings.
      In the gamma frequency range, ketamine enhances both background and evoked power,
      but decreases relative induced power. These findings support a role for NMDA
      receptors in mediating the balance between theta and gamma responses to sensory
      stimuli, with possible implications for dysfunction in schizophrenia.

PMID- 19583477
TI  - Semantic processing in the anterior temporal lobes: a meta-analysis of the
      functional neuroimaging literature.
AB  - The role of the anterior temporal lobes (ATLs) in semantic cognition is not clear
      from the current literature. Semantic dementia patients show a progressive and a
      specific semantic impairment, following bilateral atrophy of the ATLs.
      Neuroimaging studies of healthy participants, however, do not consistently show
      ATL activation during semantic tasks. Consequently, several influential theories
      of semantic memory do not ascribe a central role to the ATLs. We conducted a meta
      analysis of 164 functional neuroimaging studies of semantic processing to
      investigate factors that might contribute to the inconsistency in previous
      results. Four factors influenced the likelihood of finding ATL activation: (1)
      the use of PET versus fMRI, reflecting the fact that fMRI but not PET is
      sensitive to distortion artifacts caused by large variations in magnetic
      susceptibility in the area of the ATL; (2) a field of view (FOV) of more than 15
      cm, thereby ensuring whole-brain coverage; (3) the use of a high baseline task to
      prevent subtraction of otherwise uncontrolled semantic activation; (4) the
      inclusion of the ATL as an ROI. The type of stimuli or task did not influence the
      likelihood of ATL activation, consistent with the view that this region underpins
      an amodal semantic system. Spoken words, written words, and picture stimuli
      produced overlapping ATL peaks. On average, these were more inferior for picture
      based tasks. We suggest that the specific pattern of ATL activation may be
      influenced by stimulus type due to variations across this region in the degree of
      connectivity with modality-specific areas in posterior temporal cortex.

PMID- 19583478
TI  - Cortical projection topography of the human splenium: hemispheric asymmetry and
      individual differences.
AB  - The corpus callosum is the largest white matter pathway in the human brain. The
      most posterior portion, known as the splenium, is critical for interhemispheric
      communication between visual areas. The current study employed diffusion tensor
      imaging to delineate the complete cortical projection topography of the human
      splenium. Homotopic and heterotopic connections were revealed between the
      splenium and the posterior visual areas, including the occipital and the
      posterior parietal cortices. In nearly one third of participants, there were
      homotopic connections between the primary visual cortices, suggesting
      interindividual differences in splenial connectivity. There were also more
      instances of connections with the right hemisphere, indicating a hemispheric
      asymmetry in interhemispheric connectivity within the splenium. Combined, these
      findings demonstrate unique aspects of human interhemispheric connectivity and
      provide anatomical bases for hemispheric asymmetries in visual processing and a
      long-described hemispheric asymmetry in speed of interhemispheric communication
      for visual information.

PMID- 19583476
TI  - Neural representations and mechanisms for the performance of simple speech
      sequences.
AB  - Speakers plan the phonological content of their utterances before their release
      as speech motor acts. Using a finite alphabet of learned phonemes and a
      relatively small number of syllable structures, speakers are able to rapidly plan
      and produce arbitrary syllable sequences that fall within the rules of their
      language. The class of computational models of sequence planning and performance
      termed competitive queuing models have followed K. S. Lashley [The problem of
      serial order in behavior. In L. A. Jeffress (Ed.), Cerebral mechanisms in
      behavior (pp. 112-136). New York: Wiley, 1951] in assuming that inherently
      parallel neural representations underlie serial action, and this idea is
      increasingly supported by experimental evidence. In this article, we developed a
      neural model that extends the existing DIVA model of speech production in two
      complementary ways. The new model includes paired structure and content
      subsystems [cf. MacNeilage, P. F. The frame/content theory of evolution of speech
      production. Behavioral and Brain Sciences, 21, 499-511, 1998 ] that provide
      parallel representations of a forthcoming speech plan as well as mechanisms for
      interfacing these phonological planning representations with learned sensorimotor
      programs to enable stepping through multisyllabic speech plans. On the basis of
      previous reports, the model's components are hypothesized to be localized to
      specific cortical and subcortical structures, including the left inferior frontal
      sulcus, the medial premotor cortex, the basal ganglia, and the thalamus. The new
      model, called gradient order DIVA, thus fills a void in current speech research
      by providing formal mechanistic hypotheses about both phonological and phonetic
      processes that are grounded by neuroanatomy and physiology. This framework also
      generates predictions that can be tested in future neuroimaging and clinical case
      studies.

PMID- 19583480
TI  - The Role of Propylthiouracil in the Management of Graves' Disease in Adults:
      report of a meeting jointly sponsored by the American Thyroid Association and the
      Food and Drug Administration.

PMID- 19583479
TI  - Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early
      visual improvements and safety at 1 year.
AB  - Human gene therapy with rAAV2-vector was performed for the RPE65 form of
      childhood blindness called Leber congenital amaurosis. In three contemporaneous
      studies by independent groups, the procedure was deemed safe and there was
      evidence of visual gain in the short term. At 12 months after treatment, our
      young adult subjects remained healthy and without vector-related serious adverse
      events. Results of immunological assays to identify reaction to AAV serotype 2
      capsid were unchanged from baseline measurements. Results of clinical eye
      examinations of study and control eyes, including visual acuities and central
      retinal structure by in vivo microscopy, were not different from those at the 3
      month time point. The remarkable improvements in visual sensitivity we reported
      by 3 months were unchanged at 12 months. The retinal extent and magnitude of rod
      and cone components of the visual sensitivity between 3 and 12 months were also
      the same. The safety and efficacy of human retinal gene transfer with rAAV2-RPE65
      vector extends to at least 1 year posttreatment.

PMID- 19583485
TI  - The pros and cons of prophylactic central compartment lymph node dissection for
      papillary thyroid carcinoma.

PMID- 19583486
TI  - Effects of selective serotonin reuptake inhibitors on thyroid function in
      depressed patients with primary hypothyroidism or normal thyroid function.
AB  - BACKGROUND: Several studies with ambiguous results have examined the effects of
      selective serotonin reuptake inhibitors (SSRIs) on thyroid function. This study
      aimed to establish the effects of fluoxetine and sertraline treatments on thyroid
      function and thyroid autoimmunity in patients with major depression and primary
      hypothyroidism and in patients with major depression and normal thyroid function.
      METHODS: This was a prospective, controlled, intervention study involving 67
      subjects: 28 patients with major depression and hypothyroidism on adequate
      levothyroxine therapy randomized for treatment with fluoxetine (n = 13) or
      sertraline (n = 15); 29 patients with major depression and normal thyroid
      function treated with fluoxetine (n = 15) or sertraline (n = 14) and 10 control
      patients with hypothyroidism on adequate levothyroxine therapy without
      depression. Main outcome measures included thyrotropin, thyroxine (T(4)), free
      thyroxine, triiodothyronine (T(3)), anti-thyroid peroxidase antibodies, and
      Hamilton depression (HAM-D) rating scale. RESULTS: Patients with normal thyroid
      function who were treated with fluoxetine demonstrated a significant reduction of
      T(3) after 15 and 30 days of treatment (p = 0.034 and p = 0.011) and a
      significant reduction of T(4) throughout the intervention period (p = 0.04 after
      15 days; p = 0.015 after 30 days; and p = 0.029 after 90 days). However, all
      thyroid parameters remained within the euthyroid range. No changes were observed
      among hypothyroid patients on levothyroxine replacement therapy who were treated
      with either SSRI. The degree of improvement in depression symptoms (HAM-D rating
      scale) after 90 days of SSRI treatment was correlated with T(3) levels reduction
      among patients with normal thyroid function randomized for sertraline and among
      patients with hypothyroidism randomized for fluoxetine. T(3) levels remained
      within the euthyroid range during the study period. CONCLUSIONS: Neither
      fluoxetine nor sertraline was associated with clinically significant changes in
      thyroid function or thyroid autoimmunity in either primary hypothyroid or normal
      thyroid function patients with depression. However, results suggest that patients
      with normal thyroid function who were treated with fluoxetine are more
      susceptible to minor changes within the serotoninergic system than patients with
      hypothyroidism on the same SSRI therapy. To the best of our knowledge, this is
      the first study to demonstrate the safety of administering SSRIs in hypothyroid
      patients.

PMID- 19583487
TI  - Pediatric reference intervals for free thyroxine and free triiodothyronine.
AB  - BACKGROUND: The clinical value of free thyroxine (FT(4)) and free
      triiodothyronine (FT(3)) analysis depends on the reference intervals with which
      they are compared. We determined age- and sex-specific reference intervals for
      neonates, infants, and children 0-18 years of age for FT(4) and FT(3) using
      tandem mass spectrometry. METHODS: Reference intervals were calculated for serum
      FT(4) (n = 1426) and FT(3) (n = 1107) obtained from healthy children between
      January 1, 2008, and June 30, 2008, from Children's National Medical Center and
      Georgetown University Medical Center Bioanalytical Core Laboratory, Washington,
      DC. Serum samples were analyzed using isotope dilution liquid chromatography
      tandem mass spectrometry (LC/MS/MS) with deuterium-labeled internal standards.
      RESULTS: FT(4) reference intervals were very similar for males and females of all
      ages and ranged between 1.3 and 2.4 ng/dL for children 1 to 18 years old. FT(4)
      reference intervals for 1- to 12-month-old infants were 1.3-2.8 ng/dL. These 2.5
      to 97.5 percentile intervals were much tighter than reference intervals obtained
      using immunoassay platforms 0.48-2.78 ng/dL for males and 0.85-2.09 ng/dL for
      females. Similarly, FT(3) intervals were consistent and similar for males and
      females and for all ages, ranging between 1.5 pg/mL and approximately 6.0 pg/mL
      for children 1 month of age to 18 years old. CONCLUSIONS: This is the first study
      to provide pediatric reference intervals of FT(4) and FT(3) for children from
      birth to 18 years of age using LC/MS/MS. Analysis using LC/MS/MS provides more
      specific quantification of thyroid hormones. A comparison of the ultrafiltration
      tandem mass spectrometric method with equilibrium dialysis showed very good
      correlation.

PMID- 19583488
TI  - Cases of borderline in vitro constitutive thyrotropin receptor activity: how to
      decide whether a thyrotropin receptor mutation is constitutively active or not?
AB  - BACKGROUND: Previous in vitro data for several constitutively activating
      thyrotropin receptor (TSHR) mutations reported divergent results for the
      constitutive activity of the same mutations. Moreover, several case reports have
      highlighted the difficulties in determining whether a TSHR mutation is
      constitutively active or not. Retrospectively, this has repeatedly been the case
      for mutants with only a slight increase of basal cAMP activity. We re-examined 10
      previously described TSHR germline mutations with minor increases of basal cAMP
      activity and analyzed the influences of the cell line and vector system on the
      basal receptor activity. METHODS: TSHR mutations were characterized by
      determination of cell surface expression, cAMP accumulation, and linear
      regression analysis of constitutive activity. RESULTS: Re-examination of the
      previously described constitutively active TSHR germline mutations did not show
      constitutive activity for R310C and N670S as tested in COS-7 cells and confirmed
      constitutive activity for the other eight mutations. However, mutant N670S showed
      a slight but significant increase of basal activity measured by linear regression
      analysis when analyzed in HEK(GT) cells transiently transfected with pcDNA but
      not with the pSVL vector. This was not the case for R310C. CONCLUSIONS: Our
      findings indicate that current methods to precisely classify mutants with only a
      slight increase of the basal activity as constitutively active are limited. The
      results concerning the level of the basal activity can be influenced by the
      vector and/or the cell system. A comprehensive clinical characterization of the
      respective patients appears as a necessary and promising adjunct for the activity
      classification of these borderline mutations.

PMID- 19583489
TI  - Anaplastic thyroid carcinoma in a young woman: a rare case of survival.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but one of the most
      aggressive human cancers. It carries a dismal prognosis with average survival of
      6 months. It is characteristically diagnosed in patients older than 60 years. We
      report the case of a young patient with ATC, in whom disease-free survival
      exceeds 2 years, and review the related literature. SUMMARY: A 26-year-old woman
      presented with a rapidly growing anterior neck mass. A neck computed tomography
      scan showed a 3.5-cm left thyroid mass extending into the lateral neck. Fine
      needle aspiration biopsy showed a malignant tumor. A subsequent core biopsy
      showed an undifferentiated epithelial carcinoma. A total thyroidectomy and left
      modified radical neck dissection were performed. Histopathology and
      immunohistochemical analysis confirmed an ATC. Postoperatively, the patient
      received radiation with concurrent chemotherapy. Serial follow-up imaging studies
      showed no evidence of residual or recurrent disease or metastases, and patient
      remains alive, free of disease, over 2 years. CONCLUSION: ATC is usually a
      disease of the elderly but should be considered in the differential diagnosis of
      any patient who presents with a rapidly enlarging anterior neck mass. A rapid and
      thorough investigation should be initiated. This unusual case highlights that
      this aggressive thyroid cancer may occur in the young. It also emphasizes the
      role of aggressive surgery, if resectable.

PMID- 19583490
TI  - Inflammatory proptosis in Rosai-Dorfman disease simulating thyroid-associated
      ophthalmopathy.

PMID- 19583493
TI  - Carnosinase levels in aging brain: redox state induction and cellular stress
      response.
AB  - Carnosinase is a dipeptidase found almost exclusively in brain and serum. Its
      natural substrate carnosine, present at high concentration in the brain, has been
      proposed as an antioxidant in vivo. We investigated the role of carnosinase in
      brain aging to establish a possible correlation with age-related changes in
      cellular stress response and redox status. In addition, a stable HeLa cell line
      expressing recombinant human serum carnosinase CN1 was established. The enzyme
      was purified from transfected cells, and specific antibodies were produced
      against it. Brain expression of CN1, Hsp72, heme oxygenase-1, and thioredoxin
      reductase increased with age, with a maximal induction in hippocampus and
      substantia nigra, followed by cerebellum, cortex, septum, and striatum. Hsps
      induction was associated with significant changes in total SH groups, GSH redox
      state, carbonyls, and HNE levels. A positive correlation between decrease in GSH
      and increase in Hsp72 expression was observed in all brain regions examined
      during aging. Increased carnosinase activity in the brain can lead to decreased
      carnosine levels and GSH/GSSG ratio. These results, consistent with the current
      notion that oxidative stress and cellular damage are characteristic hallmarks of
      the aging process, sustain the critical role of cellular stress-response
      mechanisms as possible targets for novel antiaging strategies.

PMID- 19583494
TI  - RETRACTION - In Vitro Derivation of Human Sperm from Embryonic Stem Cells.
AB  - This article, "In Vitro Derivation of Human Sperm from Embryonic Stem Cells," is
      being retracted from Stem Cells and Development.    Further details will follow
      online, and in a subsequent issue of the Journal.

PMID- 19583495
TI  - Habitat use in irrigation channels by the golden venus chub (Hemigrammocypris
      rasborella) at different growth stages.
AB  - Ecological information on the golden venus chub (Hemigrammocypris rasborella
      Fowler, 1910) was collected during field surveys and used to analyze habitat use
      by this species at each growth stage. Surveys were conducted every month for
      approximately 2 years In an irrigation ditch near the Ushizu River, Kyushu
      Island, Japan. Based on the characteristic nuptial coloration of males, it was
      estimated that H. rasborella spawns between spring and summer. Size measurements
      of 2697 individuals indicated two size classes. The population of age class 1
      decreased rapidly after the spawning period. On the basis of growth patterns, the
      life cycle of H. rasborella was classified into three stages: the growth stage
      (GS) of age class 0 fish from August to November, the no-growth stage (NGS) of
      age class 0 fish from December to March, and the growing and spawning stage (GSS)
      of age class 0 and 1 fish from April to August. Habitat use by GS, NGS, and GSS
      fish was analyzed with a stepwise multiple linear regression. The average number
      of fish was negatively correlated with the presence of a concrete revetment in
      the GS; positively and negatively correlated with minimum water depth and
      submerged plants, respectively, in the NGS; and positively correlated with
      maximum water temperature in the GSS. These results suggest that maintenance of
      the water level in the fallow season and not using concrete revetments are
      essential for the conservation of this species under the present conditions in
      Japanese rice fields.

PMID- 19583496
TI  - Presoldier induction by a juvenile hormone analog in the nasute termite
      Nasutitermes takasagoensis (Isoptera: Termitidae).
AB  - The ability of JHIII and three JHAs (hydroprene, pyriproxyfen and methoprene) to
      induce presoldier differentiation was tested in a highly derived termite,
      Nasutitermes takasagoensis (Isoptera: Nasutitermitinae), and induced presoldiers
      were examined morphologically and histologically. Hydroprene was the most
      effective hormone analog for the artificial induction of presoldier
      differentiation. Principal component analysis showed that hydroprene-induced
      presoldiers had similar external gross morphology to natural presoldiers found in
      the same colony. Induced presoldiers had a long, horn-like frontal projection,
      called a nasus, on the head. A well-developed reservoir and duct of the frontal
      gland were also observed inside the head. Scanning electron micrographs showed
      that the precursory structure forming the nasus (nasus disc) was developed under
      the cuticle of hydroprene-treated individuals just prior to the molt into
      presoldiers. Morphological changes in presoldier differentiation induced by
      hydroprene seemed to occur normally, compared with those in natural presoldiers.
      Thus, the present methods shown in this study will provide opportunities to
      conduct further molecular analyses on the molecular developmental bases of nasus
      formation during soldier differentiation in higher termites.

PMID- 19583492
TI  - Redox regulation of cell survival by the thioredoxin superfamily: an implication
      of redox gene therapy in the heart.
AB  - Reactive oxygen species (ROS) are the key mediators of pathogenesis in
      cardiovascular diseases. Members of the thioredoxin superfamily take an active
      part in scavenging reactive oxygen species, thus playing an essential role in
      maintaining the intracellular redox status. The alteration in the expression
      levels of thioredoxin family members and related molecules constitute effective
      biomarkers in various diseases, including cardiovascular complications that
      involve oxidative stress. Thioredoxin, glutaredoxin, peroxiredoxin, and
      glutathione peroxidase, along with their isoforms, are involved in interaction
      with the members of metabolic and signaling pathways, thus making them attractive
      targets for clinical intervention. Studies with cells and transgenic animals have
      supported this notion and raised the hope for possible gene therapy as modern
      genetic medicine. Of all the molecules, thioredoxins, glutaredoxins, and
      peroxiredoxins are emphasized, because a growing body of evidence reveals their
      essential and regulatory role in several steps of redox regulation. In this
      review, we discuss some pertinent observations regarding their distribution,
      structure, functions, and interactions with the several survival- and death
      signaling pathways, especially in the myocardium.

PMID- 19583497
TI  - Regulation of desmin expression in adult-type myogenesis and muscle maturation
      during Xenopus laevis metamorphosis.
AB  - Isoforms of myosin heavy chain and tropomyosin convert during metamorphosis of
      Xenopus laevis with larval-to-adult remodeling of dorsal muscle (Nishikawa and
      Hayashi, 1994 , Dev. Biol. 165: 86-94). In the present study, other markers for
      muscle remodeling during metamorphosis were determined by SDS-PAGE analysis. The
      amounts of twelve muscle proteins changed remarkably during metamorphosis. Among
      these, a 54-kDa molecule was found to be desmin, and the relative content/total
      proteins decreased dramatically through metamorphosis. In hindlimb muscle, desmin
      content increased fourfold during prometamorphosis, when myoblast proliferation
      and fusion occurred. With further myotube maturation, this content decreased by
      1/2 while that of muscle actin continued to increase. Thus, desmin up- and down
      regulation in hindlimbs mark early and late phases of myogenesis, respectively.
      In tall muscle, the desmin content decreased continuously to (1/8) before and
      during metamorphosis, due to tall muscle growth and maturation. In dorsal muscle,
      three desmin changes occurred: a pre-metamorphic decrease, a transient increase
      at prometamorphosis, and a rapid decrease at the climax stage.
      Immunohistochemical analysis showed desmin+ cells to be present between young
      (adult-type) myotubes and replicating (PCNA+) cells in dorsal muscles,
      correlating the transient desmin upregulation in dorsal muscle with the
      initiation of adult-type myogenesis. After the upregulation, dorsal muscle desmin
      decreased to (1/8). This rapid down-regulation was replicated by administration
      of triiodothyronine (T3) to tadpoles, suggesting a significant role for T3 in
      dorsal muscle remodeling during metamorphosis. Collectively, these results show
      that analysis of desmin expression and PCNA-immunohistochemistry are good tools
      for determining the sites and timing of larval-to-adult muscle remodeling during
      Xenopus laevis metamorphosis.

PMID- 19583498
TI  - Placode formation and generation of gonadotropin-releasing hormone (GnRH) neurons
      in ascidians.
AB  - Neurogenic placodes, a chordate innovation, generate several neuronal
      populations, including gonadotropin-releasing hormone (GnRH) neurons which are
      crucial for vertebrate and solitary ascidian urochordate reproduction. The dorsal
      strand placode of ascidians Is derived from the anterior ridge of the embryonic
      neural plate and thus shares a common developmental origin and expression of
      various transcription factors with vertebrate placodes. Despite their importance
      for understanding vertebrate origins, the evolutionary and developmental origins
      of the neurogenic placode remain obscure. Here I demonstrate the formation of an
      elaborate neurogenic placode, which forms the dorsal strand, on part of the
      neural gland epithelium in a solitary ascidian urochordate, Halocynthia roretzi.
      Two modes of GnRH neurogenesis in the dorsal strand (a peripheral organ) and the
      migration of GnRH neurons into the brain along the visceral nerve are also
      described. Ontogenetically, GnRH neurons are first detected in the dorsal strand
      and cerebral ganglion of very young Juveniles at almost the same time,
      demonstrating that ascidians possess morphological and developmental features in
      common with vertebrates. These results further indicate that the onset of
      peripheral GnRH neurogenesis and the ability of neurons to migrate into the brain
      predate the divergence of ascidians and vertebrates. Thus, based on the
      generation of GnRH neurons, the dorsal strand in ascidians may be homologous to
      the vertebrate olfactory placode. These organs are derived from the anterior
      region of the embryonic neural plate, which expresses several transcription
      factors that invertebrate chordates and vertebrates have in common. These results
      provide unequivocal support for the clade Olfactories (tunicates + vertebrates).

PMID- 19583499
TI  - Discovery of dense aggregations of stalked crinoids in Izu-Ogasawara trench,
      Japan.
AB  - Stalked crinoids are recognized as living fossils that typically inhabit modern
      deep-water environments exceeding 100 m. Previous records of stalked crinoids
      from hadal depths (exceeding 6000 m) are extremely rare, and no in-situ
      information has been available. We show here that stalked crinoids live densely
      on rocky substrates at depths over 9000 m in the Izu-Ogasawara Trench off the
      eastern coast of Japan, evidenced by underwater photos and videos taken by a
      remotely operated vehicle. This is the deepest in-situ observation of stalked
      crinoids and demonstrates that crinoid meadows can exist at hadal depths close to
      the deepest ocean floor, in a fashion quite similar to populations observed in
      shallower depths.

PMID- 19583500
TI  - A homolog of the vertebrate thyrostimulin glycoprotein hormone alpha subunit
      (GPA2) is expressed in Amphioxus neurons.
AB  - The cystine-knot glycoprotein hormone alpha (GPA) family regulates gonadal and
      thyroid functions in vertebrates. Little is known concerning GPA family members
      in primitive chordates. A previous genomic analysis revealed the presence of two
      genes homologous to the thyrostimulin alpha subunit (GPA2) in an amphioxus
      (Branchiostoma florideae); however only one GPA2 homolog contained both the
      cystine-knot structure and N-glycosylation site characteristic of family members.
      Gene-specific PCR was used to obtain the cDNA and genomic sequences of the GPA2
      homolog of the amphioxus Branchiostoma belcheri. Whole-mount in situ
      hybridization revealed GPA2 mRNA expression in the anterior part of the nerve
      cord and on the left side of the central canal. Because amphioxus possesses only
      one true GPA2 homolog, while vertebrates possess two glycoprotein hormone alpha
      subunits (thyrostimulin alpha, or GPA2, and the common alpha subunit of gonadal
      and thyroid glycoprotein hormones, GPA1), our results suggest that GPA1 was
      acquired later in the vertebrate lineage through gene duplication.

PMID- 19583501
TI  - Morph-dependent expression and subcellular localization of host serine
      carboxypeptidase in bacteriocytes of the pea aphid associated with degradation of
      the endosymbiotic bacterium Buchnera.
AB  - Pea aphids form a mutualistic association with the endosymbiotic bacterium
      Buchnera, which is harbored in specialized host cells called bacteriocytes. The
      adult aphids display dimorphism In which there are winged and wingless morphs. We
      previously reported that the Buchnera density in bacteriocytes of the winged
      morph (alate) decreases around final ecdysis, whereas that in the wingless morph
      (aptera) does not decrease; the decrease in density in alatae is accompanied by
      activation of the host lysosomal system and by Buchnera degradation. In the
      present study, we performed a proteomic analysis to clarify the molecular
      mechanisms underlying the decrease in Buchnera density. By comparing the protein
      expression profiles of bacteriocytes in alatae and apterae Just after final
      ecdysis, we identified three and one protein spots that were preferentially
      expressed in alatae and apterae, respectively. Among the three alate-preferential
      spots, two were an identical aphid protein, carboxypeptidase vitellogenic-like
      (CPVL), whereas the other was a mixture of four proteins: gamma-glutamyl
      hydrolase, acyl-CoA dehydrogenase, aphid short chain acyl-CoA dehydrogenase, and
      Buchnera S-adenosylmethionine synthetase. The aptera-preferential spot was
      Buchnera outer membrane protein A. Immunoblot and immunohistochemical analyses
      using aphid bacteriocytes Just after final ecdysis revealed that expression of
      aphid CPVL was preferentially upregulated in alatae and was localized around
      Buchnera cells in the bacterlocytes, suggesting the involvement of CPVL in
      Buchnera degradation in alatae.

PMID- 19583502
TI  - Genetic diversity and differentiation of gray mullet (Mugil cephalus) in the
      coastal waters of Taiwan.
AB  - From mid-December to late January, schools of mature gray mullet (Mugil cephalus)
      migrate southward along the coastal waters of China to Taiwan for spawning. It
      has been proposed that there is no genetic differentiation of gray mullet in the
      coastal waters of Taiwan. To test this hypothesis, complete cytochrome b (cyt b)
      DNA sequences of 98 Individuals of gray mullet, two Individuals of Liza
      macrolepis, and three individuals of L. affinis were amplified by polymerase
      chain reaction and sequenced. Phylogenetic trees reconstructed with the Bayesian,
      maximum likelihood, maximum parsimony, and neighbor-Joining methods all support
      the existence of three monophyletic groups (denoted as groups 1, 2, and 3), with
      net evolutionary divergences (p-distances) between groups ranging from 5.1% to
      6.6%. To estimate the relative abundance of each group, a PCR-RFLP method was
      developed to examine 600 juveniles collected from October 2006 to March 2007.
      Groups 1, 2, and 3 comprised 85%, 3%, and 12% of the samples, respectively.
      Juveniles of groups 1 and 3 could be found as early as November, but Juveniles of
      group 2 were not found until February. Based on the dates of specimen collection
      and phylogenetic analyses, we propose that groups 1 and 2 are migratory
      populations from China and Japan, respectively, whereas group 3 is a resident
      population in Taiwan.

PMID- 19583503
TI  - Identification, characterization, and expression of the genes TektinA1 and
      Axonemal protein 66.0 in the tropical abalone Haliotis asinina.
AB  - The genes Tektin A1 and axonemal protein 66.0 were successfully Isolated and
      characterized in the tropical abalone Haliotis asinina. The full-length cDNAs of
      Ha-TekA1 and Ha-Axp66.0 were 2166 and 2038 bp long, with ORFs of 1350 and 1683
      bp, respectively. Both Ha-TekA1 and Ha-Axp66.0 were expressed in the testes but
      not in the ovaries or hemocytes of H. asinina adults. In addition, HaAxp66.0 was
      not expressed in H. asinina juveniles (2, 3, and 5 months old). A tissue
      expression analysis showed Ha-Axp66.0 to be expressed specifically in the testes,
      whereas Ha-TekA1 was expressed abundantly in the testes but weakly in the foot,
      gill, digestive gland, left hypobranchial gland, and mantle. The relative
      expression levels of Ha-TekA1 and Ha-Axp66.0 were significantly lower in
      undeveloped testes (stage I) than in developed testes (stages II, III, and IV) of
      H. asinina (P < 0.05).

PMID- 19583504
TI  - A new species of Philautus (Amphibia, Anura, Rhacophoridae) from the lowland of
      Sarawak, western Borneo.
AB  - A new species in the rhacophorid genus Philautus is described on the basis of
      five male specimens collected from the Matang Range, a herpetologically well
      surveyed area of the lowland of Sarawak, western Borneo. The species possesses a
      cutaneous pectoris muscle but lacks vomerine teeth, and is assigned to the
      aurifasciatus group of Philautus. It is superficially similar to some other
      species of the same group, but can be differentiated from them by a combination
      of several morphological characters, including lack of a nuptial pad and lingual
      papilla, and more significantly, by a distinct advertisement call. This discovery
      underscores the immediate necessity for detailed surveys in the already well
      explored lowlands of Borneo.

PMID- 19583506
TI  - Laparoscopic transabdominal transvesical vesicovaginal fistula repair.
AB  - BACKGROUND AND PURPOSE: Transabdominal transvesical repair has been the standard
      management for difficult vesicovaginal fistulae as a result of obstetric and
      gynecologic surgery. We describe a laparoscopic transvesical technique that
      minimizes operative morbidity. PATIENTS AND METHODS: This retrospective study
      included 25 women who underwent laparoscopic surgery for vesicovaginal fistula
      from June 2003 to November 2008. All patients were underwent laparoscopic surgery
      by the transabdominal transvesical route. Patients were investigated by
      intravenous urography, micturating cystography, cystoscopy, and retrograde
      pyelography. RESULTS: Of the 25 patients who underwent laparoscopic surgery, 3
      patients' operations had to be converted to open surgery because of dense
      adhesions. Of the 22 cases completed laparoscopically, leakage per vagina
      occurred in 3 patients. One patient underwent fulguration of residual fistula and
      was cured, one underwent vaginal repair, and other patient was lost to follow-up.
      CONCLUSIONS: Laparoscopic transvesical vesicovaginal fistula repair appears to be
      a safe and effective procedure that adheres to the principles of a transabdominal
      transvesical fistula repair while decreasing morbidity and improving cosmesis.

PMID- 19583510
TI  - Gene transcript abundance profiles distinguish Kawasaki disease from adenovirus
      infection.
AB  - BACKGROUND: Acute Kawasaki disease (KD) is difficult to distinguish from other
      illnesses that involve acute rash or fever, in part because the etiologic
      agent(s) and pathophysiology remain poorly characterized. As a result, diagnosis
      and critical therapies may be delayed. METHODS: We used DNA microarrays to
      identify possible diagnostic features of KD. We compared gene expression patterns
      in the blood of 23 children with acute KD and 18 age-matched febrile children
      with 3 illnesses that resemble KD. RESULTS: Genes associated with platelet and
      neutrophil activation were expressed at higher levels in patients with KD than in
      patients with acute adenovirus infections or systemic adverse drug reactions, but
      levels in patients with KD were not higher than those in patients with scarlet
      fever. Genes associated with B cell activation were also expressed at higher
      levels in patients with KD than in control subjects. A striking absence of
      interferon-stimulated gene expression in patients with KD was confirmed in an
      independent cohort of patients with KD. Using a set of 38 gene transcripts, we
      successfully predicted the diagnosis for 21 of 23 patients with KD and 7 of 8
      patients with adenovirus infection. CONCLUSIONS: These findings provide insight
      into the molecular features that distinguish KD from other febrile illnesses and
      support the feasibility of developing novel diagnostic reagents for KD based on
      the host response.

PMID- 19583513
TI  - Risk factors and outcomes associated with isolation of meropenem high-level
      resistant Pseudomonas aeruginosa.
AB  - OBJECTIVE: To determine risk factors and outcomes for patients with meropenem
      high-level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory
      concentration [MIC] > or = 32 microg/mL). DESIGN: Case-control-control. SETTING:
      An 867-bed urban, teaching hospital. PATIENTS: Fifty-eight MRPA case patients
      identified from an earlier P. aeruginosa study; 125 randomly selected control
      patients with meropenem-susceptible P. aeruginosa (MSPA) (MIC < or = 4
      microg/mL), and 57 control patients without P. aeruginosa (sampled by case
      date/location). METHODS: Patient data, outcomes, and costs were obtained via
      administrative database. Cases were compared to each control group while
      controlling for time at risk (days between admission and culture, or entire
      length of stay [LOS] for patients without P. aeruginosa). RESULTS: A
      multivariable model predicted risks for MRPA versus MSPA (odds ratio [95%
      confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15,
      1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53
      [1.18, 5.45]) (adj. R(2) = 0.28). For MRPA versus no P. aeruginosa, risks were
      age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40
      [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj.
      R(2) = 0.32). Other invasive devices (including mechanical ventilation) and
      previous antibiotic use (including carbapenems) were nonsignificant. MRPA
      mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at
      risk (P = .15) but did from mortality without P. aeruginosa (9%) (P = .01).
      Median LOS and costs were greater for MRPA patients versus MSPA patients and
      patients without P. aeruginosa: 30 days versus 16 and 10 (P<.01) and $88,425
      versus $28,620 and $22,605 (P<.01). CONCLUSIONS: Although antibiotic use has been
      shown to promote resistance, our data found that prior antibiotic use was not
      associated with MRPA acquisition. However, admission frequency and Foley
      catheters were, suggesting that infection control measures are essential to
      reducing MRPA transmission.

PMID- 19583514
TI  - Mixture model to assess the extent of cross-transmission of multidrug-resistant
      pathogens in hospitals.
AB  - OBJECTIVE: Creation of a mixture model based on Poisson processes for assessment
      of the extent of cross-transmission of multidrug-resistant pathogens in the
      hospital. METHODS: We propose a 2-component mixture of Poisson processes to
      describe the time series of detected cases of colonization. The first component
      describes the admission process of patients with colonization, and the second
      describes the cross-transmission. The data set used to illustrate the method
      consists of the routinely collected records for methicillin-resistant
      Staphylococcus aureus (MRSA), imipenem-resistant Pseudomonas aeruginosa, and
      multidrug-resistant Acinetobacter baumannii over a period of 3 years in a German
      tertiary care hospital. RESULTS: For MRSA and multidrug-resistant A. baumannii,
      cross-transmission was estimated to be responsible for more than 80% of cases;
      for imipenem-resistant P. aeruginosa, cross-transmission was estimated to be
      responsible for 59% of cases. For new cases observed within a window of less than
      28 days for MRSA and multidrug-resistant A. baumannii or 40 days for imipenem
      resistant P. aeruginosa, there was a 50% or greater probability that the cause
      was cross-transmission. CONCLUSIONS: The proposed method offers a solution to
      assessing of the extent of cross-transmission, which can be of clinical use. The
      method can be applied using freely available software (the package FlexMix in R)
      and it requires relatively little data.

PMID- 19583515
TI  - Molecular Characterization of Stenotrophomonas maltophilia isolates from cystic
      fibrosis patients and the hospital environment.
AB  - OBJECTIVES: To ascertain whether cystic fibrosis (CF) patients are colonized or
      infected with unique or multiple strains of Stenotrophomonas maltophilia; to
      understand whether some strains colonize or infect more than 1 patient,
      indicating clonal spread; and to explore the molecular heterogeneity of hospital
      water isolates and their correlation with clinical isolates. SETTING: The
      regional CF center of Policlinico "Umberto I" of Rome, Italy. METHODS: The study
      was carried out on a random sample of S. maltophilia isolates (n = 110) collected
      from CF patients (n = 50) during the period 2002-2005 and on 24 water isolates
      obtained during a monitoring program in the first 6 months of 2005. Home
      environmental samplings were not performed. All isolates, which were recovered
      from cultures of specimens obtained in both inpatient and outpatient settings,
      were genotyped with DNA macrorestriction analysis with the restriction enzyme
      XbaI and pulsed-field gel electrophoresis. RESULTS: One-third of the patients
      with repeated episodes of S. maltophilia infection or colonization hosted more
      than 1 strain. A potential transmission, defined as the isolation of the same
      strain in 2 or more patients, occurred 5 times, showing a frequency of potential
      transmission episodes slightly higher than previously reported. Water, taps, and
      sinks of the different rooms of the CF center tended to be persistently colonized
      with the same strain of S. maltophilia, with no correlation between clinical and
      water-associated isolates. CONCLUSIONS: The study does not provide sufficient
      data to conclude definitively that isolation of colonized or infected CF patients
      and control of hospital water systems contamination would be beneficial infection
      control measures. Epidemiologic analytical studies that correlate the presence of
      S. maltophilia with clinical outcomes are strongly needed.

PMID- 19583516
TI  - Macrolide resistance and molecular types of Treponema pallidum causing primary
      syphilis in Shanghai, China.
AB  - BACKGROUND: The resurgence of syphilis in China requires laboratories to update
      their methods for molecular epidemiology investigation and surveillance. This
      study focuses on implementing polymerase chain reaction (PCR) diagnostic tests
      for syphilis and for detection of molecular subtypes and macrolide resistance
      among strains causing primary syphilis in the city of Shanghai, China. METHODS:
      Swabs were obtained from the genital lesions of 39 patients who presented with
      symptoms compatible with primary syphilis. Eight of the patients also provided
      whole blood samples. Swabs were also obtained from 10 patients without syphilis
      who presented with genital ulcers. PCR tests to amplify 3 common but unlinked
      treponemal genes were performed on DNA samples extracted from these specimens.
      Molecular subtyping was based on genetic characterization of 2 treponemal repeat
      genes, arp and tpr. Detection of macrolide resistance was accomplished by
      identification of the 23S ribosomal RNA gene mutation associated with the
      resistance pattern. RESULTS: Thirty-eight patients with primary syphilis were
      found to have Treponema pallidum DNA in their genital lesions by PCR assays using
      primers that target the bmp, tpp-47, and polA genes. None of the patients without
      syphilis had positive PCR results. Five molecular subtypes were identified, with
      1 type (14f) causing 79% of the cases. All 38 patients were found to be infected
      with macrolide-resistant strains. CONCLUSIONS: Three common treponemal gene
      targets (bmp, tpp-47, and polA) were detectable by PCR in patients with primary
      syphilis. A single clone characterized as 14f and showing macrolide resistance
      appeared to have caused most of the primary syphilis cases in this study.

PMID- 19583517
TI  - Tuberculosis into the 2010s: is the glass half full?
AB  - During the 16 years since the World Health Organization declared tuberculosis
      (TB) a global emergency, major new challenges have emerged-in particular the
      spread of extensively drug-resistant (XDR)-TB and its overlap with human
      immunodeficiency virus infection. However, during this period, we have also
      witnessed the creation of-and major commitments from-agencies dedicated to TB
      control, research, and funding, and tangible positive achievements have occurred;
      these include improvements in both new and existing TB diagnostics, a
      developmental pipeline of new candidate TB drugs, better treatment outcomes for
      multidrug-resistant TB and XDR-TB, heightened recognition of the importance of
      nosocomial transmission, and improved strategies to reduce mortality associated
      with concurrent human immunodeficiency virus infection and TB. We suggest updates
      to the 2006 International Standards of Tuberculosis Care to embrace these
      developments. The incorporation of these recent advances into optimized directly
      observed treatment, short course (DOTS), programs, in conjunction with more
      widespread deployment and enhanced political will, all provide grounds for
      improved control.

PMID- 19583518
TI  - Long-term Escherichia coli asymptomatic bacteriuria among women with diabetes
      mellitus.
AB  - BACKGROUND: Persistent Escherichia coli asymptomatic bacteriuria (ASB) is common
      among persons with diabetes mellitus, but the duration of colonization and the
      rates of recolonization are unknown. We estimated the duration of colonization
      and the rate of recolonization among successively isolated E. coli from diabetic
      women with ASB and compared the virulence profiles with uropathogenic and
      commensal E. coli. METHODS: A total of 105 women with diabetes were enrolled in a
      randomized, controlled clinical trial for treatment of ASB in Manitoba, Canada,
      and were observed at least every 3 months for up to 3 years. We analyzed 517
      isolates from 70 women with repeated E. coli ASB for genetic similarity using
      enterobacterial repetitive intergenic consensus polymerase chain reaction. Unique
      strains were screened for uropathogenic virulence characteristics using dot blot
      hybridization and compared with different collections of E. coli isolates.
      RESULTS: On average, differences were found among women assigned to treatment for
      ASB, those treated only for symptomatic infections, and untreated women in (1)
      follow-up time with bacteriuria (29%, 31%, and 66%, respectively; P<.001), (2)
      duration of bacteriuria (2.2, 2.5, and 3.7 months, respectively; P=.04), and (3)
      carriage of unique isolates (2.4, 2.8, and 4 months, respectively; P=.03). Women
      assigned to antibiotic treatment usually had recurrent infection (76%), 64% of
      the time with a genetically new E. coli strain. Virulence characteristics of
      these isolates were comparable to those of fecal isolates from healthy women.
      CONCLUSIONS: Treatment may reduce the overall proportion of time infected in the
      long term and carriage of a unique strain, but most treatment regimens were
      followed by subsequent recolonization. Infecting strains did not have virulence
      factors characteristic of uropathogenic E. coli.

PMID- 19583519
TI  - Ongoing revolution in bacteriology: routine identification of bacteria by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - BACKGROUND: Matrix-assisted laser desorption ionization time-of-flight (MALDI
      TOF) mass spectrometry accurately identifies both selected bacteria and bacteria
      in select clinical situations. It has not been evaluated for routine use in the
      clinic. METHODS: We prospectively analyzed routine MALDI-TOF mass spectrometry
      identification in parallel with conventional phenotypic identification of
      bacteria regardless of phylum or source of isolation. Discrepancies were resolved
      by 16S ribosomal RNA and rpoB gene sequence-based molecular identification.
      Colonies (4 spots per isolate directly deposited on the MALDI-TOF plate) were
      analyzed using an Autoflex II Bruker Daltonik mass spectrometer. Peptidic spectra
      were compared with the Bruker BioTyper database, version 2.0, and the
      identification score was noted. Delays and costs of identification were measured.
      RESULTS: Of 1660 bacterial isolates analyzed, 95.4% were correctly identified by
      MALDI-TOF mass spectrometry; 84.1% were identified at the species level, and
      11.3% were identified at the genus level. In most cases, absence of
      identification (2.8% of isolates) and erroneous identification (1.7% of isolates)
      were due to improper database entries. Accurate MALDI-TOF mass spectrometry
      identification was significantly correlated with having 10 reference spectra in
      the database (P=.01). The mean time required for MALDI-TOF mass spectrometry
      identification of 1 isolate was 6 minutes for an estimated 22%-32% cost of
      current methods of identification. CONCLUSIONS: MALDI-TOF mass spectrometry is a
      cost-effective, accurate method for routine identification of bacterial isolates
      in <1 h using a database comprising > or =10 reference spectra per bacterial
      species and a 1.9 identification score (Brucker system). It may replace Gram
      staining and biochemical identification in the near future.

PMID- 19583520
TI  - Birth prevalence and natural history of congenital cytomegalovirus infection in a
      highly seroimmune population.
AB  - BACKGROUND: The natural history of congenital cytomegalovirus (CMV) infection is
      scarcely known in populations with high maternal CMV seroprevalence. This study
      evaluated the birth prevalence, clinical findings at birth, and hearing outcome
      in CMV-infected children from such a population. METHODS: Consecutively born
      infants were screened for the presence of CMV in urine and/or saliva specimens
      during the first 2 weeks after birth. Neonatal clinical findings were recorded,
      and CMV-infected children were tested to document hearing function during follow
      up. A subset of mothers of CMV-infected infants were prenatally tested for the
      presence of anti-CMV immunoglobulin G antibodies. RESULTS: Congenital CMV
      infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%)
      of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical
      finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had >3
      findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%;
      95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral
      profound hearing loss was observed in 2 children, and the hearing threshold was
      >60 decibels in all 5 children with hearing loss, including 2 children born to
      mothers with probable nonprimary CMV infection. CONCLUSIONS: The results of this
      large newborn screening study in a population with high CMV seroimmunity provide
      additional evidence that congenital CMV disease occurs in populations with high
      seroprevalence rates, with a similar incidence of CMV-related hearing loss to
      that reported in the offspring of women from populations in developed countries
      with lower rates of seroimmunity to CMV.

PMID- 19583533
TI  - Initialization, conceptualization, and application in the generalized
      (fractional) calculus.
AB  - This paper provides a formalized basis for initialization in the fractional
      calculus. The intent is to make the fractional calculus readily accessible to
      engineering and the sciences. A modified set of definitions for the fractional
      calculus is provided which formally include the effects of initialization.
      Conceptualizations of fractional derivatives and integrals are shown. Physical
      examples of the basic elements from electronics are presented along with examples
      from dynamics, material science, viscoelasticity, filtering, instrumentation, and
      electrochemistry to indicate the broad application of the theory and to
      demonstrate the use of the mathematics. The fundamental criteria for a
      generalized calculus established by Ross (1974) are shown to hold for the
      generalized fractional calculus under appropriate conditions. A new generalized
      form for the Laplace transform of the generalized differintegral is derived. The
      concept of a variable structure (order) differintegral is presented along with
      initial efforts toward meaningful definitions.

PMID- 19583534
TI  - Perceptions concerning hip resurfacing from attendees at the Second Annual U.S.
      Comprehensive Course on Total Hip Resurfacing Arthroplasty.
AB  - Resurfacing hip arthroplasty represents a new, alternative technology to standard
      total hip arthroplasty. We examined the perceptions about resurfacing after the
      Second Annual United States Comprehensive Course on Total Hip Resurfacing
      Arthroplasty, which was a multi-company sponsored educational event to advance
      general knowledge, basic science, and surgical skills relevant to this field. The
      course led to a substantial increase in knowledge concerning resurfacing as
      evaluated from pre- and post-tests. The perceptions concerning indications,
      patient selection, and beliefs of the course attendees are reported.

PMID- 19583535
TI  - A comparison of total hip resurfacing and total hip arthroplasty - patients and
      outcomes.
AB  - A comparison of pertinent preoperative and postoperative data relative to total
      hip resurfacing versus total hip arthroplasty (THA) would assist in evaluating
      current perceptions in outcome. We compared 50 consecutive metal-metal
      resurfacing replacements in 50 patients with 44 consecutive conventional total
      hip arthroplasties in 35 patients, who were implanted during the same time
      period, by the same surgeon, and followed prospectively for 2 to 4 years. The
      patients undergoing hip resurfacing were 62% male, 9 years younger, and 3.2
      inches taller, with a lower mean body mass index and American Society of
      Anesthesiologists (ASA) grade than patients undergoing total hip arthroplasty.
      Preoperatively, patients undergoing resurfacing had a lower Harris hip score (46
      vs 52 points), more pain, higher UCLA (University of California at Los Angeles)
      activity scores (4.2 vs 3.6), and better range of motion. Surgical time for
      resurfacing was 18% longer, but there was less total blood loss and fewer
      transfusions. Postoperatively, there was no difference in Harris hip score (97 vs
      96). Patients undergoing resurfacing had higher function, Short Form-12 physical
      activity scores, and UCLA activity scores, but also a higher incidence of slight
      or mild pain. There were no differences in postoperative range of motion or
      dislocation (one each). The preoperative characteristics and general health
      status of the average patient undergoing resurfacing are more favorable than that
      of the average patient undergoing conventional total hip arthroplasty. Caution
      should be applied in attributing differences in outcomes directly to the
      arthroplasty technology.

PMID- 19583536
TI  - Minimally invasive hip resurfacing compared to minimally invasive total hip
      arthroplasty.
AB  - BACKGROUND: Since its March 2006 FDA approval in the United States, Birmingham
      hip resurfacing (BHR) has been a popular alternative to hip arthroplasty for the
      younger patient population. Data to date has shown a trend toward low incidence
      of dislocation and good survivorship. METHODS: 128 patients operated on by a
      single surgeon from July 2006 to December 2008 were reviewed for complications,
      pain, and function. A group of single incision, minimally invasive standard total
      hip replacements (106 cases) in 2008 was used for comparison of the same
      outcomes. CONCLUSION: Pain, function, and total Harris Hip scores were all
      improved by the 2 year mark and better than the total hip group. Overall incision
      lengths decreased over the study time period. The average age of the BHR
      recipient was 51 years, approximately 14 years less than the total hip mean age.
      Pain in the Birmingham group improved by 32 points at the 3 month mark. By the
      end of 2 years, the Birmingham group Harris Hip score mean was nearly perfect at
      98.5 points. Rare incidence of complications, marked decreased pain scores and
      marked elevation in function were results found in this sample of Birmingham
      resurfacing.

PMID- 19583537
TI  - Resurfacing matched to standard total hip arthroplasty by preoperative activity
      levels - a comparison of postoperative outcomes.
AB  - BACKGROUND: Some studies have suggested that resurfacing patients are generally
      more active postoperatively than their conventional total hip arthroplasty
      (THA)counterparts, but controversy remains over whether this is a reflection of
      preferential use of resurfacing for younger and higher-activity patients. We
      hypothesized that, when controlling for preoperative activity levels, in addition
      to relevant clinical and demographic factors, resurfacing provides similar
      results to conventional hip arthroplasty. MATERIALS AND METHODS: The specific
      question asked was whether resurfacing patients had differences in postoperative
      activity level, clinical outcomes, or rate of revisions, as compared to a matched
      cohort of patients treated with conventional THA. Thirty-three patients (23 men
      and 10 women) who were treated with resurfacing arthroplasties were matched to a
      cohort of patients who underwent conventional hip arthroplasty by gender, age,
      body mass index (BMI), and preoperative activity level. Mean preoperative Harris
      hip scores and length of follow-up were similar for the two groups. Postoperative
      weighted activity scores, Harris hip scores, patient satisfaction score, pain
      scores, and revision rates were evaluated at a mean final follow-up of 42 months
      (range, 25 to 68 months) for the resurfacing group and 45 months (range, 24 to 67
      months) for the conventional hip group, and analyzed for differences. RESULTS: At
      final follow-up, activity levels were significantly higher in the resurfacing
      group, with a mean weighted activity score of 10.0 points (range, 1.0 to 27.5
      points), as compared to a mean score of 5.3 points (range, 0 to 12.0 points) in
      the THA group. Mean Harris hip scores, patients satisfaction scores, and pain
      scores were similar for both groups. There were no revisions in either group.
      CONCLUSIONS: The results of this study suggest that patients treated with hip
      resurfacing arthroplasty have a significantly higher postoperative activity
      level, as compared to those treated with conventional THA, when controlled for
      preoperative factors.

PMID- 19583538
TI  - Resurfacing versus conventional total hip arthroplasty - review of comparative
      clinical and basic science studies.
AB  - OBJECTIVE: Although standard total hip arthroplasties have a long and successful
      history as the standard of care for advanced, symptomatic osteoarthritis, there
      is increasing patient demand and surgeon interest in femoral bone conserving
      resurfacing alternatives. The purpose of this study was to assess the state of
      the research that directly compares the outcomes of conventional total hip
      arthroplasty procedures with the current generation of metal-on-metal resurfacing
      hip arthroplasties. METHODS: A comprehensive review was performed of the
      published literature that directly compared total hip arthroplasty and
      resurfacing hip arthroplasty and that considered basic science, radiographic, and
      clinical studies. RESULTS: Of the basic science studies, two investigations found
      evidence that favored total hip arthroplasty, while three favored resurfacing hip
      arthroplasty. For the clinical studies, all reports showed that resurfacing hip
      arthroplasty had similar or better outcomes than total hip arthroplasty at short-
      to midterm follow-up. The gait studies suggest that resurfacing provides a more
      natural gait than conventional total hip arthroplasty. CONCLUSIONS: While there
      is still much debate and room for additional research on this topic, multiple
      midterm clinical results suggest that resurfacing hip arthroplasty represents a
      safe, effective alternative to conventional total hip arthroplasty, especially
      for younger, active patients.

PMID- 19583539
TI  - Canadian academic experience with metal-on-metal hip resurfacing.
AB  - The current depth and breadth of experience in hip resurfacing in Canadian
      academic centers is not well known. This study endeavors to increase awareness of
      the prevalence of programs and current experience in a select number of
      representative teaching centers by examining the learning curve of high-volume
      surgeons. A questionnaire was sent to all academic centers in Canada to identify
      the volume of hip resurfacing, surgical approach, and type of prosthesis. In
      addition, five surgeons, not fellowship-trained in hip resurfacing, were selected
      for a detailed review of their first 50 cases, including survey of patient
      demographics, surgical approach, radiographic evaluation, complications, and
      revision. Eleven of 14 academic centers are currently performing hip resurfacing.
      All of these centers had performed more than 50 cases, with 10 of 11 of them
      having more than one surgeon performing the procedure. The posterior approach was
      found to be the most commonly utilized in surgeries. The overall revision rate
      was 3.2% at a mean time of 2 years, with femoral neck fracture (1.6%) being the
      most common cause for failure. The failure rate was comparable to other centers
      of expertise and lower than previously published multicenter trials. All surgeons
      reviewed were in specialized arthroplasty practices, which may contribute to the
      relatively low complication rates reported.

PMID- 19583541
TI  - Extra-articular deformities and the role of hip resurfacing - a proposed
      classification system.
AB  - There has been an increasing demand for hip resurfacing as an alternative to
      total hip arthroplasty. A number of reports have been published recently
      detailing the technique and role of resurfacing in a variety of extra-articular
      deformities, dysplastic conditions, and settings of retained intramedullary
      hardware and other impediments. The following report proposes a classification
      system that recognizes intramedullary and extramedullary deformities. With the
      long-term expectation for resurfacing, these complex situations may require
      categorization to segregate risk factors in order to allow for better planning
      and prognostication.

PMID- 19583540
TI  - The early results of metal-on-metal hip resurfacing - a prospective study at a
      minimum two-year follow-up.
AB  - Hip resurfacing has recently been offered as an attractive alternative to
      conventional total hip arthroplasty. This report evaluated the short-term
      functional outcome and longevity of a newer generation resurfacing device and
      includes the results of 228 consecutive hip resurfacing in 209 patients at a
      minimum of two-year follow-up. All resurfacing were performed by a single surgeon
      using a posterior approach. Excluding infections, there were only three failures
      (1.3%). The overall survival at 4.6 years was 96.9%. The survival of resurfacing
      in this study was comparable to that of other published studies of hip
      resurfacing. Surface hip arthroplasty appears to be an effective alternative to
      conventional total hip arthroplasty in patients suffering from osteoarthritis.

PMID- 19583542
TI  - Resurfacing arthroplasty for patients with osteonecrosis.
AB  - The suitability of third-generation metal-on-metal hip resurfacing products for
      patients with a primary diagnosis of osteonecrosis has been debated. The
      preservation of femoral head bone stock for femoral prosthetic support is
      essential for the long-term stability of implants. A modern hip resurfacing
      system was implanted in 1148 hips as part of a United States multicenter
      investigational device exemption study. Of these, 116 hips had a preoperative
      diagnosis of osteonecrosis and were compared to 1023 hips with osteoarthritis.
      Survival rates were not significantly different (95.9% and 95.8% at 24 months for
      osteoarthritis and osteonecrosis respectively, p = 0.46). Resurfacing
      arthroplasty for patients with osteonecrosis appears to be a reasonable
      alternative, taking into consideration implant size, patient gender, and size of
      femoral deficiency. Further characterization is needed to identify those specific
      patients with osteonecrosis for whom resurfacing arthroplasty would be
      appropriate.

PMID- 19583543
TI  - Hip resurfacing-keys to success.
AB  - In recent years, metal-on-metal hip resurfacing has become an increasingly
      popular treatment for patients needing hip arthroplasty. Important factors to
      consider for a successful outcome include proper patient selection and surgical
      technique, including approach, component positioning, and cementing technique.
      This review will serve as guide to both those who are learning the technique of
      hip resurfacing and to more experienced surgeons.

PMID- 19583544
TI  - Cement technique changes improved hip resurfacing longevity - implant retrieval
      findings.
AB  - BACKGROUND: Most designs of metal-on-metal hip resurfacing utilize cement for
      femoral fixation, but the amount, application, and distribution of cement varies
      considerably according to implant design and surgeon preference. In one type of
      hip resurfacing system (Conserve Plus), the objective was to achieve a 1-mm
      cement mantle and several millimeters of penetration. In early cases of the
      senior investigator's (HCA) series, cement fixation failures were noted, and this
      prompted changes in femoral head preparation and cement application techniques.
      Survivorship improved following implementation of these changes. The aim of the
      current study was to examine revised femoral components for the cement
      distribution, especially in cases where the improved techniques were subsequently
      applied. METHOD: Fifteen resurfacing femoral components were sectioned and the
      slices were radiographed and photographed, and the amount and distribution of
      cement were examined and measured. Cases representative of the evolving cementing
      techniques were examined in detail. RESULTS: There was considerable variation
      observed in the amount and distribution of cement, partly as a consequence of
      variable bone quality in this "all-comers" included series. The cement analyses
      showed that the newer cementing techniques helped to reduce over-penetration
      while providing better cement interdigitation. The use of extra fixation holes
      and cementing the stem in cases with poor bone quality were associated with
      improved cement-to-bone contact area. CONCLUSION: Meticulous femoral head
      preparation was helpful in providing durable cement fixation and is essential in
      cases with poor bone quality.

PMID- 19583545
TI  - Quantifying degree of difficulty in hip - resurfacing of pistol-grip deformity.
AB  - This study used computer simulation to endeavor to quantify the relative degree
      of difficulty of resurfacing femora with pistol-grip deformities compared to
      relatively normal femora. Computer models of five pistol-grip femora and one
      relatively normal femur were computed from computed tomography (CT) scans of
      patients who had undergone computer-assisted hip resurfacing. A computer
      simulation of positioning the femoral resurfacing component on the femur was
      performed to count the number of acceptable configurations of the component on
      the femur. A high number of acceptable configurations implies that the surgeon
      has greater freedom, or greater margin for error, in implanting the component
      compared to a femur with a smaller number of acceptable configurations. We found
      that pistol-grip deformities dramatically reduce the number of acceptable
      configurations for valgus alignment, and that such configurations result in
      decreased femoral offset and increased depth of reaming.

PMID- 19583546
TI  - Computer navigated hip resurfacing for patients with abnormal femoral anatomy.
AB  - Hip resurfacing is a technically demanding alternative to total hip arthroplasty.
      The use of traditional jigs for placement of the femoral guidewire can lead to
      preparatory errors that may predispose the resurfacing construct to premature
      failure. Computer navigation is a tool that can be used to minimize the incidence
      of inadequate to detrimental preparation of the femoral head and improve the
      accuracy of component placement. Computer navigation not only shows promise in
      routine cases of hip resurfacing but also in those cases that are technically
      challenging. The current study demonstrated the utility of imageless computer
      navigation in placement of the femoral component for patients presenting with
      abnormal femoral anatomy.

PMID- 19583547
TI  - Computer-assisted navigation in hip resurfacing arthroplasty - a single-surgeon
      experience.
AB  - Hip resurfacing arthroplasty is a technically challenging procedure, and
      orientation of the femoral component is critical to avoid implant failure. The
      use of computer-assisted navigation has been shown to decrease the learning curve
      for beginners in hip resurfacing and to improve the surgeon's ability to produce
      consistent results. Computer navigation offers real-time feedback, with the
      opportunity to produce improved repeatability to optimize patient outcomes. The
      purpose of this study was to evaluate the learning curve of computer-assisted
      surgery in the hands of an experienced hip resurfacing surgeon. A retrospective
      review of 100 consecutive navigated hip resurfacing arthroplasties in 94 patients
      assessed preoperative and postoperative neck-shaft angles, operative times, and
      complications. Twenty-five non-navigated hip resurfacing arthroplasties,
      performed by the same surgeon, were evaluated as a matching group. Mean operative
      times for the computer-assisted hip resurfacing were 101 minutes, as compared to
      104 minutes in the non-navigated group. We found that in the hands of an
      experienced hip resurfacing surgeon, the addition of computer-assisted navigation
      had no effect on the learning curve, but did provide feedback and repeatability
      to the surgeon.

PMID- 19583548
TI  - Evaluation of persistent pain after hip resurfacing.
AB  - Evaluation and treatment of pain following hip resurfacing arthroplasty can be
      challenging, even for the most experienced arthroplasty surgeon. As in any total
      hip replacement, there are a number of investigative tools at the disposal of
      orthopaedic surgeons to elicit the underlying causes of pain for diagnosis and
      treatment. A detailed history and physical examination are the most important
      first steps in the differential diagnosis of the intrinsic and extrinsic
      etiologies of hip pain. Serial radiographs from the time of surgery also should
      be reviewed and compared for changes indicative of loosening, migration, and
      osteolysis, in combination or alone. Diagnostic injections with local anesthetic
      agents additionally can be performed to localize the origin of pain. Bone
      scintigraphy, hip joint aspiration, and laboratory tests, including erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP), should be requested
      routinely to exclude an occult infection. The use of ultrasound (US), magnetic
      resonance imaging (MRI), and even hip arthroscopy has been suggested as potential
      diagnostic tools when metal sensitivity is suspected. Relative to cause, femoral
      neck fractures and the possibility of metal hypersensitivity as sources of
      persistent groin pain should always be considered in metal-on-metal hip
      resurfacing. Additionally, iliopsoas tendinopathy and anterior impingement of the
      femoral neck are well-recognized causes of pain and should be included in the
      differential diagnosis. Surface arthroplasty is becoming an acceptable
      alternative to standard total hip replacement in young patients. It is
      increasingly essential to recognize the different causes of pain following
      resurfacing in order to make an accurate diagnosis and initiate timely,
      appropriate treatment.

PMID- 19583549
TI  - Posterior femoroacetabular impingement (PFAI) - after hip resurfacing
      arthroplasty.
AB  - INTRODUCTION: The recent, encouraging outcome literature on hip resurfacing
      arthroplasty (HRA) has not sufficiently examined the potential occurrence of
      postoperative femoroacetabular impingement (PFAI) and sequelae. The current study
      asks the questions, "Does femoroacetabular impingement occur after hip
      resurfacing arthroplasty (HRA) and, if so, what are the clinical outcomes?"
      METHODS: Sixty-nine consecutive hips in 57 patients with a minimum of 2 years
      clinical and radiographic follow-up were evaluated. Both acetabular and femoral
      component positions and postsurgical changes in the femoral neck and acetabulum
      were recorded. RESULTS: Fourteen hips in 13 patients (20%) developed a small
      scalloped, corticated erosion in the posterior neck, just distal to the femoral
      component and adjacent to the acetabular component rim. These erosions were
      between 5 and 10 mm in depth and became apparent at an average of 15 months
      (range, 6 to 24 months) following surgery. After 2 years, they showed no further
      progression. The location and shape of the erosions indicate PFAI as the
      etiology. One hip also demonstrated similar changes in the anterior neck. The
      Harris Hip Score and UCLA (University of California at Los Angeles) Activity
      Scores were higher in patients with such erosions (97.5 and 9.2, respectively),
      compared to those patients without (93.5 and 8.4, respectively). Additionally,
      patients with erosions reported slightly better pain relief on average than
      patients with no radiographic evidence of impingement. No significant differences
      in range of motion or component position were found between the two groups.
      CONCLUSIONS: Small, corticated, non-progressive erosions can occur from
      femoroacetabular impingement following HRA. The erosions were more commonly
      posterior in this series, and they tended to occur in active patients. There is
      no adverse effect on clinical outcomes, and more specifically, there is no
      association of PFAI with pain.

PMID- 19583550
TI  - Range of motion after stemmed total hip arthroplasty and hip resurfacing - a
      clinical study.
AB  - Range of motion after total hip arthroplasty is becoming an important topic as
      today's patients present at a younger age and are more active. An effective study
      design to carry out comparisons of clinical performance between two implants
      should eliminate patient-related extraneous variables (e.g., age, gender,
      activity level, among others). The aim of the present study was to compare the
      range of motion results achieved postoperatively between metalon-metal hip
      resurfacing (HR) and conventional total hip arthroplasty (THA) in a cohort of
      bilateral patients implanted with both designs. Thirty-five patients who had
      undergone bilateral surgery with one hip receiving an HR device and the
      contralateral hip receiving a THA were retrospectively selected. Sixty-nine
      percent of the patients were male, and at the time of implantation of the
      resurfacing device the mean age of the patients was 53 years. The mean follow-up
      time was 88 months for the hips treated with HR and 96 months for the hips that
      received a THA. We found no difference in any of the range of motion measurements
      between HR and THA even after separating the cohort into two groups based on the
      femoral head size of the THA (femoral heads under 40 mm and femoral heads greater
      or equal to 40 mm). Our investigation showed that, for most patients, prosthetic
      design is unlikely to be a limiting factor of range of motion after surgery
      provided that the positioning of the acetabular component is adequate.

PMID- 19583551
TI  - Biologic effects of implant debris.
AB  - Biologic response to orthopedic implants debris is central to clinical
      performance. Eventual implant loosening due to aseptic osteolysis has been
      attributed to local inflammatory responses to wear and corrosion products that
      are produced by articulating implant interfaces. The response to implant debris
      is dominated by local immune activation, e.g. macrophages. Immune reactivity has
      been shown to depend on the number of particles produced or the dose (i.e., the
      concentration of phagocytosable particles per tissue volume, which can be
      characterized by knowing the size distribution and amount of debris). Elongated
      particles (fbers) are generally more pro-inflammatory than round particles, and
      there is a growing consensus that metals particles are more proinflammatory than
      polymers in vivo. Generally, to produce an in vitro inflammatory response,
      particles need to be less than 10 mum, i.e. phagocytosable. However, both soluble
      and particulate debris derived from Co-Cr-Mo alloy implants can induce
      monocyte/macrophage activation and secretion of pro-inflammatory cytokines such
      as IL-1beta, TNFalpha, IL-6 and IL-8 via up-regulation of transcription factor
      NFkappabeta, and activation of inflammasome danger signaling in human
      macrophages. Not only does activation of local (and systemic) inflammation result
      in decreased osteoblast function but osteoclast activity increases. Some people
      are more predisposed to implant debris induced inflammation and metal "allergy"
      testing services are becoming available. New pathways of implant debris-induced
      inflammatory reactions continue to be discovered, such as the "danger signaling"
      inflammasome pathway, which provides new targets for pharmaceutical intervention
      and improved implant performance.

PMID- 19583552
TI  - The problem with large diameter metal-on-metal acetabular cup inclination.
AB  - Large diameter metal-on-metal hip bearings have proven to be clinically
      successful in active patients, but, in a small number, they are associated with
      elevated wear and high metal ion levels when cup inclination angles are too steep
      and the version is too extreme, or either alone. Based on the geometry of six
      different commercially available large diameter metal-on-metal acetabular
      components, this study demonstrated that the critical bearing surface operates at
      an angle up to 16 masculine greater than the cup face inclination. Due to
      geometry alone, measured cup inclination is not the angle that most surgeons
      perceive it to be. We strongly recommend when employing large diameter metal-on
      metal bearings that lower inclination and version angles are targeted to prevent
      excessive wear.

PMID- 19583553
TI  - Methods to analyze real-world databases and registries.
AB  - Observational studies, administrative database studies, and registries offer a
      wealth of real-world information, if designed, maintained, and analyzed according
      to appropriate observational study methodology. This review summarizes basic
      observational study methods employed in rheumatology and highlights several
      notable examples. In response to growing interest in real-world effectiveness and
      safety data, registries are expected to proliferate in the near future. The
      availability of detailed clinical information in registries coupled with powerful
      tools for analysis offers promise for timely and accurate information on the
      safety and effectiveness of rheumatic treatments.

PMID- 19583554
TI  - Evidence-based medicine and the Cochrane Collaboration.
AB  - Providing evidence-based care to patients involves turning a clinical problem
      into an answerable question, systematically searching for the best evidence
      relevant to the question, critically appraising that evidence, and, finally,
      using the evidence as the basis for clinical decisions to solve the problem.
      While the overload of medical information today presents a demanding challenge to
      physicians to sort and identify relevant and valid evidence, it is vitally
      important to translate that evidence into clinically useful terms. To apply
      evidence to patient clinical management, it is critical to discuss with patients
      the evidence, the benefits and the harms, and the alternative treatments, such
      that they understand and can fully participate in the decision-making process.
      The framework of evidenced-based medicine provides a concrete methodology to
      address these issues, here, framed and detailed in five steps. The Cochrane
      Collaboration has been at the forefront of applying the methods of evidence-based
      medicine (EBM) in the treatment and management of musculoskeletal and other
      disorders.

PMID- 19583555
TI  - Diagnostic versus classification criteria - a continuum.
AB  - The current understanding that disease criteria are different than classification
      criteria is not well founded. In fact, they are a continuum. The arithmetic
      behind the two are the same and is built on a clear understanding of the concepts
      of sensitivity and specificity. Diagnosis is nothing different than
      classification in the individual patient. The main element that makes a set of
      criteria diagnostic is the pretest odds. We should question our current practice
      of making universal disease criteria and perhaps design criteria tailored to
      subspecialties.

PMID- 19583556
TI  - Safety reporting in randomized clinical trials - a need for improvement.
AB  - The reporting of adverse events (AEs) in randomized clinical trials (RCTs) is
      often lacking in the publication of trials. Part of the problem is the way safety
      data are reported in RCTs. Reporting of "time to event," use of standardized
      incidence ratios for comparison to normal population or disease controls, use of
      "patient years" when reporting AE, and adequate sample size and power
      calculations are some of the problems that need to be addressed and improved in
      RCTs.

PMID- 19583557
TI  - RAPID3-an index of physical function, pain, and global status as "vital signs" to
      improve care for people with chronic rheumatic diseases.
AB  - A guide to RAPID3 (routine assessment of patient index data), an index of three
      patient self-report measures-physical function, pain, and patient global estimate
      of status-on a multidimensional health assessment questionnaire (MDAQ) is
      presented, including development, scoring, use in standard care, and rationale.
      RAPID3 and its individual components are regarded as "vital signs," which may
      alert a health professional to unsuspected patient problems, provide a baseline
      measure to support a change in therapy, and numerically document improvement or
      worsening over time to complement clinical impressions. MDHAQ-RAPID3 can be
      incorporated into the infrastructure of standard rheumatology care for completion
      in the waiting room by every patient with any rheumatic disease at every visit:
      if there is a reason for a visit, there is a reason for RAPID3 vital signs.
      RAPID3 is calculated in 5 to 10 seconds, providing similar information to DAS28
      (disease activity score) and CDAI (clinical disease activity index), which
      require a mean of 114 and 106 seconds, respectively. MDHAQ-RAPID3 presents an
      additional advantage for the patient to optimize the office encounter by
      completion of the questionnaire in the waiting room. The MDHAQ also includes a
      review of systems and recent medical history, which can save 2 to 3 minutes per
      visit for other patient concerns. A physician's clinical decisions ultimately
      require synthesis and interpretation of all available data, ranging from
      laboratory tests to patient questionnaire scores. RAPID3 vital signs can
      contribute to this synthesis toward improved quality, outcomes, and documentation
      of rheumatology care.

PMID- 19583558
TI  - What can we learn from design faults in the Women's Health Initiative randomized
      clinical trial?
AB  - Design faults resulted in the inability of the Women's Health Initiative (WHI)
      randomized clinical trial to test the level of cardioprotection conferred by
      timely hormone treatment of women seeking help for menopausal complaints.
      Adopting a design constructed around the avoidance of symptomatic subjects and
      recruitment of older subjects who were more likely to manifest cardiovascular
      events during the life of the WHI resulted in recruitment of older, sicker
      subjects than are normally treated for complaints around the time of menopause.
      The lack of cardioprotection in subjects that began treatment a decade or more
      after menopause diluted cardioprotection in subjects starting treatment close to
      the menopausal transition. As a result, despite having the largest number of
      subjects ever, there were not enough women in the WHI who were comparable to
      those in the observational trials that showed cardioprotection. This led the WHI
      to report that there was no cardioprotection in the trial, a position that has
      been qualified after further analysis. Misapprehension of the initial WHI
      conclusions by the media, professionals, and regulatory agencies led to a major
      shift away from menopausal hormone treatment. This remains problematic since the
      evidence continues to favor cardioprotection and other benefits that are denied
      under present regulations and guidelines. Regulatory agencies and professional
      organizations need to better understand the faws in the WHI design and results in
      order to properly consider its results and the sustainability of their earlier
      conclusions and recommendations. Additionally, new trials are needed to test the
      validity of menopausal hormone-related cardioprotection.

PMID- 19583559
TI  - Arthritis as a risk factor for incident coronary heart disease in elderly
      Japanese-American males - the Honolulu Heart Program.
AB  - BACKGROUND: Arthritis is the most common chronic disease in the elderly. Studies
      show that rheumatoid arthritis is a risk factor for cardiovascular morbidity and
      mortality, and osteoarthritis is associated with an unfavorable cardiovascular
      risk factor profile. METHODS: At the Honolulu Heart Program's fourth examination
      in 1991 to 1993, arthritis status was assessed among a cohort of 3741 Japanese
      American males, ages 71 to 93 years. Arthritis was determined by self-report of
      physician diagnosis, and subjects were divided into two groups: current arthritis
      and no current arthritis. Eight years of follow-up data are available for
      incident coronary heart disease (CHD) in 2777 subjects free of CHD at baseline.
      Age-adjusted rates of incident CHD and means of cardiovascular risk factors were
      compared in each group. Cox proportional hazards models were used to calculate
      relative risks, adjusting for common cardiovascular risk factors, alcohol, and
      use of aspirin or NSAIDs, or both. RESULTS: There were 279 cases of incident CHD
      in the cohort over 8 years; in those with arthritis, 11.7% developed incident
      CHD, compared to 9.8% in those without arthritis (p = 0.24). Age-adjusted rates
      of incident CHD in those with and without arthritis were 20.5 and 18.0 per 1000
      person-years, respectively (p = 0.25). Arthritis was not significantly associated
      with CHD risk factors. Arthritis was not a significant independent predictor of
      incident CHD (relative risk, 1.06; 95% CI, 0.74 to 1.51). CONCLUSIONS: Arthritis,
      and most probably osteoarthritis, may not be associated with most CHD risk
      factors or 8-year incident CHD in elderly Japanese-American males.

PMID- 19583560
TI  - Monitoring response to therapy in rheumatoid arthritis - perspectives from the
      clinic.
AB  - The major objectives in treating patients with rheumatoid arthritis are managing
      the symptoms of disease and preserving joint structure, with the ultimate goal of
      disease remission. Several independent studies have shown that treatment
      decisions driven by quantitative rather than subjective monitoring of disease
      activity result in significantly improved patient outcomes. Various assessment
      tools are available that measure both clinical and patient-reported outcomes.
      While some measurement tools may be more appropriate for use in clinical trials,
      several have been developed that are simple and practical to use, even in a busy
      clinic. As pivotal members of the multidisciplinary rheumatology healthcare
      provider team, the nurse and the rheumatologist play key roles in managing a
      patient's progress by closely monitoring their response to treatment. Here, we
      discuss optimal disease management founded on a multidisciplinary approach and
      provide an overview of some key measures for assessing patient response to
      treatment.

PMID- 19583561
TI  - Multifocal IOLs: a euphoric personal report. strabismus surgery in thyroid
      ophthalmopathy, management of the "lost" medial rectus muscle; superior oblique
      tuck complications.

PMID- 19583562
TI  - The NOT crisis in health care. The Cost "Issue" is all the fault of our congress
      and our government anyway. "Reform" is a four letter word. Reform Congress! How
      they can and should reduce costs. Our part to help.

PMID- 19583563
TI  - Standard strabismus surgery in thyroid ophthalmopathy.
AB  - INTRODUCTION: Techniques for the surgical treatment of thyroid related strabismus
      vary and include non-adjustable (standard), [postop'] adjustable suture, and a
      newer procedure aimed at correcting restriction rather than using dose/response
      tables.This study reports the results utilizing standard strabismus procedures
      for the treatment of thyroid ophthalmopathy. METHODS: Charts of 31 consecutive
      patients who underwent surgery in the pst 5 years for restrictive strabismus
      secondary to thyroid ophthalmopathy were retrospectively reviewed. All surgery
      was performed by recession and reattachment of the muscle to the globe, allowing
      for no postoperative adjustment. Standard doses were used for all primary surgery
      and slightly modified in some cases of reoperation, but the general principal was
      from a standard published nomogram. RESULTS: All 31 patients had preoperative
      diplopia and restricted motility. 22 patients wore prisms prior to surgery. Of
      the 31 patients who underwent surgery 9 required a second operation. After
      reoperation 5 patients (16%) continued to have diplopia. However, 4 of these
      patients were able to achieve single binocular vision with a small amount of
      prism. Only 2 patients were unable to achieve single binocular vision with or
      without prism. 22 patients (71%) had full ocular motility after surgery. After
      one surgery, 25 of 31 patients (81%) were satisfied with the results of surgery.
      This increased to 29 patients (94%) after reoperation. CONCLUSION: The results of
      this study indicated that strabismus surgery for restrictive thyroid
      ophthalmopathy using standard technique and table amounts of surgery can provide
      excellent results and patient satisfaction.

PMID- 19583564
TI  - Tenon's capsule pseudo-tendon repair of a lost medial rectus muscle.
AB  - BACKGROUND AND PURPOSE: The loss of an extraocular muscle is an infrequent but
      serious complication of strabismus surgery. The purpose is to show that a
      tailored tongue of Tenon's capsule, 7.0 mm to 9.0 mm wide and 12.0 mm to 14.0 mm
      long, fashioned in the direction of a lost medial rectus muscle and attached at
      the site of its original insertion can restore full ocular movement in the
      direction of action of the muscle. CASE REPORT: Thisis a report of a patient who
      underwent re-shaping and attachment of Tenon's capsule to the original insertion
      of the medial rectus muscle that ruptured during attempted medial rectus
      recession for longstanding esotropia with medial rectus restriction. The
      procedure was done immediately following the loss and failure to retrieve the
      lost muscle. RESULTS: Residual large angle esotropia and good adduction were
      obtained postoperatively despite a severed and consecutively lost medial rectus
      muscle. CONCLUSION: A tongue of Tenon's capsule, attached at the original site of
      a lost extraocular rectus muscle in a young adult, works as a pseudo-tendon
      successfully restoring function in the direction of action of that muscle.

PMID- 19583565
TI  - Extrusion of non-absorbable suture from a superior oblique tuck without loss of
      surgical effect.
AB  - BACKGROUND: Superior oblique tuck is an effective procedure for the treatment of
      superior oblique palsy. There has been no report of the extrusion of the non
      absorbable suture typically used in this procedure. We describe a case of late
      extrusion of the non-absorbable suture used in a superior oblique tuck. RESEARCH
      DESIGN: Case report. CASE REPORT: A 4 year old boy underwent a successful left
      superior oblique tuck for a left superior oblique palsy. Eleven months after
      surgery, the non-absorbable suture used forf the tuck extruded coincidentally
      with ocular trauma. The suture was slightly adherent to a suture granuloma in the
      supranasal quadrant of the left eye and removed without loss of surgical effect
      of the superior oblique tuck. CONCLUSION: Late extrusion of a non-absorbable
      suture used in a superior oblique tuck may not result in loss of surgical effect.
      However, this finding does not imply the acceptability of using an absorbable,
      instead of a non-absorbable, suture in this procedure.

PMID- 19583566
TI  - Oxygen: a master regulator of pancreatic development?
AB  - Beyond its role as an electron acceptor in aerobic respiration, oxygen is also a
      key effector of many developmental events. The oxygen-sensing machinery and the
      very fabric of cell identity and function have been shown to be deeply
      intertwined. Here we take a first look at how oxygen might lie at the crossroads
      of at least two of the major molecular pathways that shape pancreatic
      development. Based on recent evidence and a thorough review of the literature, we
      present a theoretical model whereby evolving oxygen tensions might choreograph to
      a large extent the sequence of molecular events resulting in the development of
      the organ. In particular, we propose that lower oxygenation prior to the
      expansion of the vasculature may favour HIF (hypoxia inducible factor)-mediated
      activation of Notch and repression of Wnt/beta-catenin signalling, limiting
      endocrine cell differentiation. With the development of vasculature and improved
      oxygen delivery to the developing organ, HIF-mediated support for Notch
      signalling may decline while the beta-catenin-directed Wnt signalling is
      favoured, which would support endocrine cell differentiation and perhaps exocrine
      cell proliferation/differentiation.

PMID- 19583567
TI  - Newly formed E-cadherin contacts do not activate Cdc42 or induce filopodia
      protrusion in human keratinocytes.
AB  - BACKGROUND INFORMATION: The appropriate regulation of cell-cell adhesion is an
      important event in the homoeostasis of different cell types. In epithelial cells,
      tight adhesion mediated by E-cadherin receptors is essential for the
      differentiation and functionality of epithelial sheets. Upon assembly of cadherin
      mediated cell-cell contacts, it is well established that the small GTPases Rho
      and Rac are activated and are necessary for junction stability. However, the role
      of the small GTPase Cdc42 in cadherin adhesion is less clear. Cdc42 can be
      activated by E-cadherin in a breast tumour cell line, but the requirement for
      Cdc42 function for new junction assembly or maintenance has been contradictory.
      Cdc42 participation in cell-cell contacts has been inferred from the presence of
      filopodia, the typical F-actin structure induced by Cdc42 activation, as cells
      approach each other to establish cell-cell contacts. Yet, under these conditions,
      the contribution of migration to filopodia protrusion cannot be excluded and the
      results are difficult to interpret. RESULTS: In the present study, we set out to
      address (a) whether Cdc42 is activated by new E-cadherin cell-cell contacts when
      junction assembly occurs without prior migration and (b) whether Cdc42 function
      is necessary for cadherin stability. We found that junction formation in
      confluent keratinocytes or upon E-cadherin clustering decreased Cdc42-GTP levels.
      In the absence of serum- and migration-induced Cdc42 activation, we demonstrated
      that cell-cell contacts do not induce filopodia or require Cdc42 function to
      assemble. CONCLUSION: We conclude that Cdc42 does not participate in the early
      events that initiate stable cadherin adhesion in keratinocytes. Yet, it is
      feasible that Cdc42 may be activated at later time points or by other receptors.
      Cdc42 can then participate in additional functions during polarization, such as
      Golgi re-positioning or basolateral trafficking.

PMID- 19583568
TI  - Promoting assembly and bundling of FtsZ as a strategy to inhibit bacterial cell
      division: a new approach for developing novel antibacterial drugs.
AB  - FtsZ plays an essential role in bacterial cell division. We have used the
      assembly of FtsZ as a screen to find antibacterial agents with a novel mechanism
      of action. The effects of 81 compounds of 29 different structural scaffolds on
      FtsZ assembly in vitro were examined using a sedimentation assay. Out of these 81
      compounds, OTBA (3-{5-[4-oxo-2-thioxo-3-(3-trifluoromethyl-phenyl)-thiazolidin-5
      ylidenemethyl]-furan-2-yl}-benzoic acid) was found to promote FtsZ assembly in
      vitro. OTBA increased the assembly of FtsZ, caused bundling of FtsZ
      protofilaments, prevented dilution-induced disassembly of FtsZ protofilaments and
      decreased the GTPase activity in vitro. It bound to FtsZ with an apparent
      dissociation constant of 15+/-1.5 microM. Furthermore, OTBA inhibited the
      proliferation of Bacillus subtilis 168 cells with an MIC (minimum inhibitory
      concentration) of 2 microM, whereas it exerted minimal effects on mammalian cell
      proliferation, indicating that it might have a potential use as an antibacterial
      drug. In the effective proliferation inhibitory concentration range, OTBA induced
      filamentation in bacteria and also perturbed the formation of the cytokinetic Z
      rings in bacteria. However, the agent neither perturbed the membrane structures
      nor affected the nucleoid segregation in B. subtilis cells. The results suggested
      that the OTBA inhibited bacterial cytokinesis by perturbing the formation and
      functioning of the Z-ring via altering FtsZ assembly dynamics. The antibacterial
      mechanism of action of OTBA is similar to that of the widely used anticancer drug
      paclitaxel, which inhibits cancer cell proliferation by promoting the assembly of
      tubulin, a eukaryotic homologue of FtsZ.

PMID- 19583570
TI  - Sublingual traumatic ulceration (a Riga-Fede disease): report of two cases.
AB  - Sublingual traumatic ulceration is rare and a benign, ulcerative and
      granulomatous process that occurs as a result of repetitive trauma of the oral
      mucosal surfaces by the teeth. Treatment should begin conservatively and should
      focus on eliminating the source of the trauma. In our cases, we chose the
      conservative treatment by grinding the teeth and placing composite resin over the
      offending teeth and applied orabase. At the follow-up, we confirmed that the
      lesion was resolved and infant was feeding normally.

PMID- 19583569
TI  - Matrix metalloproteinase-2 predicts mortality in patients with acute coronary
      syndrome.
AB  - The aim of the present study was to investigate the predictive value of MMP
      (matrix metalloproteinase)-2, MMP-3 and MMP-9 levels in patients with acute
      coronary syndrome for death, readmission with HF (heart failure) or recurrent MI
      (myocardial infarction) and to compare them with established markers, NT-proBNP
      (N-terminal pro-B-type natriuretic peptide) and the GRACE (Global Registry of
      Acute Coronary Events) score. A single blood test was taken 4 days after
      admission in 1024 consecutive patients with acute MI with end points observed
      over 519 (134-1059) days [value is median (range)]. MMP-2 and MMP-3 were
      increased in patients who died (n=111) compared with survivors (P<0.006 and
      P=0.01 respectively), but were similar in patients with HF (n=106) or MI (n=138).
      MMP-9 levels were similar across study end points. Using Cox proportional hazards
      modelling, MMP-2 demonstrated an independent prediction of death [HR (hazard
      ratio) 6.60, P=0.001], along with NT-proBNP (HR 4.62, P<0.001) and the GRACE
      score (HR 1.03, P<0.001), but MMP-3, MMP-9 or log10-troponin I did not. For 1
      year mortality, the areas under the receiver operating characteristic curves were
      0.60 and 0.58 for MMP-2 and MMP-3 respectively, compared with 0.82 for NT-proBNP
      and 0.84 for the GRACE score (all P<0.001). Kaplan-Meier analysis revealed that
      MMP-2 levels in the top quartile were associated with higher mortality rates (log
      rank 12.49, P=0.006). On univariate analysis, MMP-2 and MMP-3 had a weak
      association with HF readmission, which was lost after adjustment for clinical
      factors. None of the MMPs tested predicted MI. In conclusion, this is the first
      single centre study that identifies MMP2 as an independent predictor of all-cause
      mortality post-ACS (acute coronary syndrome); however, NT-proBNP and the GRACE
      score are superior for risk stratification in this cohort.

PMID- 19583571
TI  - Further development of a scientific journal.

PMID- 19583572
TI  - Rigidity of commonly used dental trauma splints.
AB  - BACKGROUND/AIMS: The stability of immobilization devices varies from flexible to
      rigid, depending on the trauma. We evaluated the rigidity of various commonly
      used splints in vitro MATERIAL AND METHODS: An acrylic resin model was used. The
      central incisors simulated injured teeth, with increased vertical and horizontal
      mobility. The lateral incisors and canines stimulated uninjured teeth. Tooth
      mobility was measured with the Periotest device. Vertical and horizontal
      measurements were made before and after splinting, and the difference between
      values was defined as the splint effect. We evaluated 4 composite splints, 3 wire
      composite splints, a titanium trauma splint, a titanium ring splint, a bracket
      splint, and 2 Schuchardt splints RESULTS: For all injured teeth and all splints,
      there was a significant splint effect for the vertical and horizontal dimensions
      (P < 0.05). For injured teeth, the composite splints produced the largest changes
      in vertical tooth mobility; wire-composite splints 1 and 2, using orthodontic
      wires, produced the smallest vertical splint effects. For uninjured teeth, the
      Schuchardt 1 splint and the bracket splint produced the largest splint effects;
      wire-composite splints 1 and 2 produced only a slight change in tooth mobility.
      Composite splints 2 and 3 produced the largest horizontal splint effects for
      injured teeth, and the 4 composite splints produced the largest horizontal splint
      effects for uninjured teeth. The most horizontally flexible splints were the
      titanium trauma splint and wire-composite splints 1 and 2. CONCLUSIONS: According
      to the current guidelines and within the limits of an in vitro study, it can be
      stated that flexible or semirigid splints such as the titanium trauma splint and
      wire-composite splints 1 and 2 are appropriate for splinting teeth with
      dislocation injuries and root fractures, whereas rigid splints such as wire
      composite splint 3 and the titanium ring splint can be used to treat alveolar
      process fractures.

PMID- 19583574
TI  - Influence of custom-made mouth guards on strength, speed and anaerobic
      performance of taekwondo athletes.
AB  - The purpose of this study was to test the influence of custom-made mouth guards
      on strength and anaerobic performance of taekwondo athletes. The study included
      21 (11 male and 10 female) trained subjects participating in taekwondo. Anaerobic
      power and anaerobic capacity, isokinetic quadriceps and hamstring strength,
      handgrip strength, isometric lower extremity and back strength, 20 m sprint time,
      squat and counter movement jumping height were measured in two randomized
      conditions: with or without custom-made (CM) mouth guards. No significant
      differences were observed between the two conditions (with or without CM mouth
      guards) in 20 m sprint time, jumping tests, handgrip strength, isometric leg or
      back strength. On the other hand, peak power and average power in Wingate
      Anaerobic Test and Hamstring Isokinetic Peak Torque significantly increased as a
      result of wearing mouth guard (P < 0.05). In conclusion, we can suggest that
      taekwondo athletes can use CM mouth guards without any negative effects on their
      strength and anaerobic performance.

PMID- 19583573
TI  - Effectiveness of limited cone-beam computed tomography in the detection of
      horizontal root fracture.
AB  - To compare the diagnostic accuracy of conventional film radiography, charge
      coupled device (CCD) and photostimulable phosphor plate (PSP) digital images and
      limited cone-beam computed tomography in detecting simulated horizontal root
      fracture. Root fractures were created in the horizontal plane in 18 teeth by a
      mechanical force and fragments were relocated. Another 18 intact teeth with no
      horizontal root fracture served as a control group. Thirty-six teeth were placed
      in the respective empty maxillary anterior sockets of a human dry skull in groups
      three by three. Intraoral radiographs were obtained in three different vertical
      views by utilizing Eastman Kodak E-speed film, CCD sensor, RVG 5.0 Trophy and a
      PSP sensor Digora, Optime. Cone beam CT images were taken with a unit (3D
      Accuitomo; J Morita MFG. Corp, Kyoto, Japan). Three dental radiologists
      separately examined the intraoral film, PSP, CCD and cone beam CT images for the
      presence of horizontal root fracture. Specificity and sensitivity for each
      radiographic technique were calculated. Kappa statistics was used for assessing
      the agreement between observers. Chi-square statistics was used to determine
      whether there were differences between the systems. Results were considered
      significant at P < 0.05. Cone beam CT images revealed significantly higher
      sensitivities (P < 0.05) than the intraoral systems between which no significant
      differences were found. Specificities did not show any statistically significant
      differences between any of the four systems. The kappa values for inter-observer
      agreement between observers (four pairs) ranged between 0.82-0.90 for the 3DX
      evaluations and between 0.63-0.71 for the different types of intraoral images.
      Limited cone beam CT, outperformed the two-dimensional intraoral, conventional as
      well as digital, radiographic methods in detecting simulated horizontal root
      fracture.

PMID- 19583575
TI  - Knowledge of lay people and dentists in emergency management of dental trauma.
AB  - The multidisciplinary nature of the follow-up evaluations of traumatic dental
      injuries (TDI) requires that both the lay public and practitioners possess
      knowledge of the treatment strategies involved. The aim of this paper was to
      assess the level of knowledge of elementary public schoolteachers, parents and
      dentists of the city of Joacaba, Southern Brazil, about the emergency management
      of TDI. Three independent cross sectional studies were carried out involving
      samples of elementary public schoolteachers (n = 245), parents (n = 107) and
      dentists (n = 85) in the city in 2001. Data were collected through structured
      interviews for schoolteachers and dentists, and questionnaires for parents,
      containing questions about socio-demographic characteristics and about incidents
      resulting in TDI. The responses in the three studies showed a wide variability of
      indicated procedures for the situations of TDI proposed. The results of
      association studies showed that older schoolteachers (P = 0.003), older dentists
      (P = 0.013) and dentists who had graduated more recently (P = 0.032) chose
      significantly more correct answers in some TDI incidents. The answers of
      schoolteachers, parents and dentists showed a wide variability of indicated
      procedures for the situations proposed. The great majority of them would not
      follow the approaches most recommended in the literature. A greater importance
      should be placed on TDI through educational campaigns aiming schoolteachers and
      parents and also through undergraduation and postgraduation dental curricula in
      order of improving its management.

PMID- 19583576
TI  - Healing process of incisor teeth of diabetic rats replanted after storage in
      milk.
AB  - Several local factors that influence the healing process of replanted teeth have
      been investigated. However, it remains unclear how systemic alterations, such as
      diabetes mellitus, affect the prognosis of these cases. The purpose of this study
      was to evaluate the healing process of incisors of non-controlled diabetic rats
      replanted after storage in bovine long shelf-life (UHT) whole milk. Thirty-two
      rats were randomly assigned to receive an endovenous injection of either citrate
      buffer solution (group I - control; n = 16) or streptozotocin dissolved in
      citrate buffer solution to induce diabetes (group II; n = 16). After confirmation
      of the diabetic status by analysis of the glycemic levels, the maxillary right
      incisor of each animal was extracted and immersed in milk for 60 min. The root
      canals of teeth were then instrumented, and were filled with a calcium hydroxide
      based dressing and replanted into their sockets. All animals received systemic
      antibiotic and were killed by anesthetic overdose 10 and 60 days after
      replantation. The specimens containing the replanted teeth were removed, fixed,
      decalcified, and embedded in paraffin. Semi-serial 6-microm-thick sections were
      obtained and stained with hematoxylin and eosin for histologic and histometric
      analyses. The results showed that the connective tissue adjacent to the root
      surface was less organized in the diabetic animals than in the control animals in
      both periods; the root dentin was less severely affected by root resorption in
      the diabetic rats; there were no significant differences between the control and
      diabetic groups regarding the occurrence of replacement resorption and
      inflammatory resorption.

PMID- 19583577
TI  - Traumatic dental injuries in individuals with cerebral palsy.
AB  - BACKGROUND: Cerebral palsy (CP) is one of the most frequent conditions
      encountered in the daily practice of dentists who treat special-needs individuals
      and it seems that traumatic dental injuries are often present in these cases. The
      aim of this study was to investigate and describe the prevalence related to
      traumatic dental injury (TDI) in individuals with CP attending rehabilitation
      treatment at the Lar Escola Sao Francisco Rehabilitation Center in Sao Paulo,
      Brazil. MATERIAL AND METHODS: The sample included 100 individuals with a medical
      diagnosis of CP (SG) aged 1-15 years (mean 7 years 2 months +/-SD 3 years 4
      months) and 100 non-disabled individuals (CG), aged 1-15 years (mean 7 years 5
      months +/- SD 4 years 0 month), presenting the same socioeconomic level as SG.
      Data were collected through clinical examinations according to Andreasen criteria
      and interviews. RESULTS: According to the Gross Motor Function Classification,
      the SG presented 34.0% of individuals that walked with or without assistive
      mobility devices and 66.0% required a wheelchair for mobility. The TDI prevalence
      observed for CG was 32.0% (n = 32), with 20.0% (n = 20) for SG, showing no
      statistically significant difference (P = 0.053). For both groups, the teeth most
      affected were the maxillary central incisors. Crown fracture without pulp
      exposure was the most frequent type of injury (31.2%) in CG and enamel fracture
      (30.0%), in SG. The groups differed significantly regarding dental treatment
      received after TDI (P = 0.012), with CG presenting higher percentages of treated
      individuals CONCLUSIONS: The data suggest that the TDI prevalence in individuals
      presenting CP and attending rehabilitation treatment was similar compared with
      non-disabled individuals, but they received less treatment.

PMID- 19583578
TI  - First-aid knowledge about tooth avulsion among dentists, doctors and lay people.
AB  - In avulsion, teeth are bodily displaced out of the bony socket. Boys, aged 7-9
      years, are most prone to avulsion of maxillary central incisors. Tooth avulsion
      should ideally be treated with immediate replantation. Because of the urgency in
      treatment, personnel dealing with this injury should have knowledge about the
      first-aid treatment. This study was conducted to assess the first-aid knowledge
      about tooth avulsion among dentists, doctors, students, school teachers and the
      general public in Lahore, Pakistan. Data were collected using a form with one
      open-ended question about the first-aid treatment of traumatic avulsion.
      Immediate replantation of the avulsed tooth was suggested by 10.1% of 377
      respondents. Among dentists, 45.8% suggested immediate replantation, with the
      rest suggesting transport of the tooth to a dentist for replantation. Among all
      other groups (non-dentists) immediate replantation was suggested by 4.6% and
      transport to a dentist by 3.3%. Non-dentists in Pakistan, including doctors, have
      insufficient knowledge about the immediate treatment of tooth avulsion. Dentists,
      in comparison, have significantly more knowledge, but may need training in
      selection of the appropriate treatment option and handling and care of the
      avulsed tooth.

PMID- 19583579
TI  - Evaluating the knowledge of sports participants regarding dental emergency
      procedures.
AB  - Dental trauma is a common consequence of sports practice to which emergency
      treatment is critical. The purpose of this study was to evaluate the knowledge of
      sports participants about dental trauma procedures, particularly tooth avulsion.
      A specific questionnaire concerning concepts, experiences and behaviors after
      dental trauma and the use of mouthguard was standardized and validated with 80
      people. The validated questionnaire was then distributed to 310 sports
      participants. The results showed that 28.4% had experienced a kind of dental
      trauma; 42.6% would look for a dentist for treatment; 51.7% reimplanted or would
      reimplant the avulsed tooth; 6.5% would maintain the avulsed tooth in milk.
      Although 47.4% of the participants were aware of the possibility of accidents
      during sports practice, only 13.9% reported to use a mouthguard. This study
      showed an overall lack of knowledge of sportsmen and sportswomen with regards to
      tooth avulsion, thus reinforcing the need for educational campaigns to improve
      the immediate emergency treatment of tooth avulsion.

PMID- 19583580
TI  - Traumatic injuries to permanent teeth in Turkish children, Ankara.
AB  - The aim of this study was to identify the types and etiologies of dento-alveolar
      injuries among patients who were treated for injuries to maxillary and/or
      mandibular permanent teeth at the Gulhane Medical Academy, Department of
      Pediatric Dentistry, Center of Dental Sciences in Ankara, Turkey to provide a
      basis for determining optimal treatment approaches and educational needs. From a
      total of 4956 children aged 6-12 years (mean age: 8.91 +/- 1.95) applying to the
      Center, 472 children (9.5%) were found to have suffered dental injuries during a
      period of 2 years. Injuries were classified according to drawings and texts based
      on the WHO classification system, as modified by Andreasen and Andreasen. Injury
      rates were highest among children age 6 and ages 8-10. The most frequently
      injured permanent teeth were the maxillary central incisors (88.2%), and the
      maxillary right central permanent incisor made up 47.2% of all injured teeth. The
      most common cause of dental trauma was falling while walking or running (40.3%).
      Most injuries involved a single tooth (64.8%). The most common type of injury was
      enamel fracture (44.6%). There was a significant difference in gender, where boys
      more often suffered from a dental hard tissue and pulp injury than girls (P =
      0.019), whereas there was no difference in gender (P = 0.248) in the distribution
      of periodontal injuries. Injuries were found to occur more frequently during the
      summer (P < 0.001). Children with increased overjet were 2.19 times more likely
      to have dental injuries than other children. Considering that the incidence of
      traumatic dental injury is highest among children ages 6 and ages 8-10 as well as
      the fact that patients with increased overjet are more prone to dental trauma,
      preventive orthodontic treatment in early mixed dentition may play an important
      role in reducing traumatic dental injuries.

PMID- 19583581
TI  - Orthodontic reduction of a displaced alveolar fracture: a case study.
AB  - A 42-year-old woman had sustained a severe dental trauma with an alveolar
      fracture after an epileptic attack. A tooth block 31, 32, 33 and 34 was
      dislocated about 7 mm in buccal direction. Panoramic X-rays and CT-scan disclosed
      the alveolar fracture without total disjunction of the fragment. An orthodontic
      appliance was used to reduce the fracture with gentle forces during a 5-month
      period. Normal function was established and the teeth remained vital.

PMID- 19583582
TI  - Decoronation of an ankylosed permanent incisor: alveolar ridge preservation and
      rehabilitation by an implant supported porcelain crown.
AB  - Replacement resorption and ankylosis are frequently diagnosed following severe
      dental trauma. The complications that may develop as a result of ankylosis of a
      permanent incisor in children and adolescent include: esthetic compromise,
      orthodontic complications because of: arch irregularity; lack of mesial drift;
      tilting of adjacent teeth, arch length loss and local arrest of alveolar ridge
      growth. To avoid such complications, an ankylosed tooth should be removed before
      the changes become so pronounced that they compromise future prosthetic
      treatment. The purpose of this article was to present a case of preservation of
      the alveolar ridge for implant rehabilitation by utilizing decoronation for the
      treatment of a young permanent central incisor. An implant was inserted, without
      any bone augmentation procedures, followed by prosthetic porcelain crown
      rehabilitation. We conclude that treatment of an ankylosed young permanent
      incisor by decoronation may maintain the alveolar bone ridge width, height and
      continuity, and facilitate future rehabilitation with minimal, if any, ridge
      augmentation procedures.

PMID- 19583583
TI  - Invalid results because of inappropriate statistical analyses. Treatment
      recommendations still in question.

PMID- 19583585
TI  - Incorrect citation suggests an opinion opposite to our conviction: a
      clarification.

PMID- 19583587
TI  - Avoiding unscheduled transcription in shared promoters: Saccharomyces cerevisiae
      Sum1p represses the divergent gene pair SPS18-SPS19 through a midsporulation
      element (MSE).
AB  - The sporulation-specific gene SPS18 shares a common promoter region with the
      oleic acid-inducible gene SPS19. Both genes are transcribed in sporulating
      diploid cells, albeit unevenly in favour of SPS18, whereas in haploid cells grown
      on fatty acids only SPS19 is highly activated. Here, SPS19 oleate-response
      element (ORE) conferred activation on a basal CYC1-lacZ reporter gene equally in
      both orientations, but promoter analysis using SPS18-lacZ reporter constructs
      with deletions identified a repressing fragment containing a midsporulation
      element (MSE) that could be involved in imposing directionality towards SPS19 in
      oleic acid-induced cells. In sporulating diploids, MSEs recruit the Ndt80p
      transcription factor for activation, whereas under vegetative conditions, certain
      MSEs are targeted by the Sum1p repressor in association with Hst1p and Rfm1p.
      Quantitative real-time PCR demonstrated that in haploid sum1Delta, hst1Delta, or
      rfm1Delta cells, oleic acid-dependent expression of SPS18 was higher compared
      with the situation in wild-type cells, but in the sum1Delta mutant, this effect
      was diminished in the absence of Oaf1p or Pip2p. We conclude that SPS18 MSE is a
      functional element repressing the expression of both SPS18 and SPS19, and is a
      component of a stricture mechanism shielding SPS18 from the dramatic increase in
      ORE-dependent transcription of SPS19 in oleic acid-grown cells.

PMID- 19583588
TI  - The word style "groundwater" reflects increased public awareness of the resource.

PMID- 19583589
TI  - Citation and acceptance of the 2008 M. King Hubbert Award.

PMID- 19583590
TI  - Citation and acceptance of the 2008 Robert Storm Interdivisional Cooperation
      Award.

PMID- 19583591
TI  - KT3D_H2O: a program for kriging water level data using hydrologic drift terms.
AB  - It is often necessary to estimate the zone of contribution to, or the capture
      zone developed by, pumped wells: for example, when evaluating pump-and-treat
      remedies and when developing wellhead protection areas for supply wells. Tonkin
      and Larson (2002) and Brochu and Marcotte (2003) describe a mapping-based method
      for estimating the capture zone of pumped wells, developed by combining universal
      kriging (kriging with a trend) with analytical expressions that describe the
      response of the potentiometric surface to certain applied stresses. This Methods
      Note describes (a) expansions to the technique described by Tonkin and Larson
      (2002); (b) the concept of the capture frequency map (CFM), a technique that
      combines information from multiple capture zone maps into a single depiction of
      capture; (c) the development of a graphical user interface to facilitate the use
      of the methods described; and (d) the integration of these programs within the
      MapWindow geographic information system environment. An example application is
      presented that illustrates ground water level contours, capture zones, and a CFM
      prepared using the methods and software described.

PMID- 19583592
TI  - A user interface for the Kansas Geological Survey slug test model.
AB  - The Kansas Geological Survey (KGS) developed a semianalytical solution for slug
      tests that incorporates the effects of partial penetration, anisotropy, and the
      presence of variable conductivity well skins. The solution can simulate either
      confined or unconfined conditions. The original model, written in FORTRAN, has a
      text-based interface with rigid input requirements and limited output options. We
      re-created the main routine for the KGS model as a Visual Basic macro that runs
      in most versions of Microsoft Excel and built a simple-to-use Excel spreadsheet
      interface that automatically displays the graphical results of the test. A
      comparison of the output from the original FORTRAN code to that of the new Excel
      spreadsheet version for three cases produced identical results.

PMID- 19583593
TI  - Molecular cloning and characterization of soybean protein disulfide isomerase
      family proteins with nonclassic active center motifs.
AB  - Protein disulfide isomerase (PDI) and other PDI family proteins are members of
      the thioredoxin superfamily and are thought to play important roles in disulfide
      bond formation and isomerization in the endoplasmic reticulum (ER). The exact
      functions of PDI family proteins in plants remain unknown. In this study, we
      cloned two novel PDI family genes from soybean leaf (Glycine max L. Merrill cv.
      Jack). The cDNAs encode proteins of 520 and 523 amino acids, and have been
      denoted GmPDIL-3a and GmPDIL-3b, respectively. GmPDIL-3a and GmPDIL-3b are the
      first plant ER PDI family proteins reported to contain the nonclassic redox
      center motif CXXS/C, and both proteins are ubiquitously expressed in the plant
      body. However, recombinant GmPDIL-3a and GmPDIL-3b did not function as
      oxidoreductases or as molecular chaperones in vitro, although a proportion of
      each protein formed complexes in both thiol-dependent and thiol-independent ways
      in the ER. Expression of GmPDIL-3a and GmPDIL-3b in the cotyledon increased
      during seed maturation when synthesis of storage proteins was initiated. These
      results suggest that GmPDIL-3a and GmPDIL-3b may play important roles in the
      maturation of the cotyledon by mechanisms distinct from those of other PDI family
      proteins.

PMID- 19583594
TI  - In this issue: treatment-refractory chronic migraine.

PMID- 19583595
TI  - Images from headache: atypical cluster headache secondary to giant meningioma.

PMID- 19583596
TI  - Expert opinion: adherence to prophylactic migraine medication.

PMID- 19583598
TI  - Clinical review and epidemiology of headache disorders in US service members:
      with emphasis on post-traumatic headache.
AB  - Migraine or headache is a common problem in the active duty population, in the
      recently deployed service members, and is a cardinal symptom of traumatic brain
      injury. While there is increasing appreciation of the clinical burden of post
      traumatic headache (PTHA) in the military traumatic brain injury population,
      there remain significant research gaps related to the epidemiology of PTHA,
      including lack of understanding of natural history, whether there are
      predisposing factors that predict the development or prognosis of headache post
      trauma and, most basically, the features that distinguish PTHA from other forms
      of chronic headache. Although diagnostic criteria for PTHA are included in the
      International Classification of Headache Disorders, 2nd edition, revised, these
      criteria are somewhat arbitrary and were not empirically defined. This lack of
      precision about the PTHA phenotype limits the rigor of observational studies of
      PTH but does not appear to significantly hamper treatment, provided the treatment
      involves a multi-modality approach.

PMID- 19583599
TI  - From psychoneurosis to ICHD-2: an overview of the state of the art in post
      traumatic headache.
AB  - Post-traumatic headache (PTH) is an important public health issue - head injuries
      are common, headache is the most common sequelae of head injuries, and PTH can be
      particularly disabling. Fortunately, for most individuals with PTH, the headache
      gradually dissipates over a period of several days, weeks, or months either
      spontaneously or aided by non-pharmacologic and/or pharmacologic management.
      Regrettably, for a minority of head-injured individuals, the PTH is intractable
      and disabling despite aggressive and comprehensive treatment. Unfortunately,
      there are many prejudices against individuals with PTH. Frequently, the presence
      or absence of litigation and/or the mechanism of head injury (sports-related
      trauma, slip-and-fall injury, motor vehicle accident, or military service-related
      injury) biases physicians' views on the legitimacy of the patient's PTH.
      Accordingly, this review attempts to summarize the state of the art of our
      understanding of PTH. This clinical review highlights: (a) views on PTH
      throughout the last few centuries, (b) the ICHD-2 classification of PTH, (c) the
      epidemiology of head injuries and PTH, (d) the clinical characteristics of PTH,
      (e) PTH related postconcussive symptoms, (f) pathophysiology of PTH, (g)
      evaluation of PTH, and (h) management of PTH.

PMID- 19583600
TI  - Post-traumatic headache: commentary: an overview.
AB  - The history of post-traumatic headache begins in the middle of the 19th century,
      and its latest iteration has been defined in the International Headache
      Classification of 2004. Contrary to the latter, there are instances when mild
      head injury without symptoms or signs of concussion may evoke the
      pathophysiological changes of migraine. The mechanisms of chronic post-traumatic
      headache and the associated syndrome are complex and include pathophysiological,
      psychological, and socioeconomic factors. Treatment of these headaches is similar
      to that of the primary headaches with particular attention to nonpharmacological
      measures.

PMID- 19583602
TI  - Migraine aura.

PMID- 19583603
TI  - Increased leukocyte aggregates are associated with atherosclerosis in patients
      with hemodialysis.
AB  - Little data are available on the role of blood rheology in atherosclerosis in
      hemodialysis (HD) patients. This study sought to assess the relationship between
      leukocytes conjugated with platelets (leukocyte aggregates [LA]) and
      atherosclerosis in patients with HD. The present study included 118 patients on
      HD. As surrogate markers of atherosclerosis, aortic stiffness measured by
      brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were
      measured. As an assessment of LA, a method, microchannel array flow analyzer,
      which makes it possible to directly observe the flow of blood cell elements
      through the microchannel, was used. We measured a number of LA during 50 microL
      flow of whole blood through microchannels. In 12 age-matched healthy individuals,
      a number of LA during 50 microL flow of whole blood was 25.7+/-5.4, whereas in HD
      patients it was significantly increased up to 48.2+/-16.4 (P<0.001). Flow
      cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates
      were positively associated with plasma levels of fibrinogen (P<0.01), or serum
      high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant
      associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001).
      In conclusion, we demonstrated hemorheologically that monocyte-platelet
      conjugates play an important role in aortic stiffness and IMT in HD patients.

PMID- 19583604
TI  - The relationship between laboratory-based outcome measures and mortality in end
      stage renal disease: a systematic review.
AB  - Despite data that traditional laboratory-based outcome measures in dialysis are
      improving over time, population-based data indicate that mortality rates are not
      improving in parallel. With increased focus on performance measures based on
      laboratory-based outcomes (e.g., hematocrit, albumin, and parathyroid hormone),
      less emphasis has been placed on other markers, some of which may be stronger
      predictors of mortality. We performed a systematic review to interpret the
      predictive value of laboratory-based outcome measures in dialysis. We identified
      studies with data regarding the predictive value of laboratory-based outcomes for
      mortality in dialysis. We calculated the sample size-weighted pooled relative
      risk of death with dichotomized "high" vs. "low" levels of each measure. We rank
      ordered predictors by scaling the pooled relative risk of each measure by its
      pooled standard deviation. There were 5171 titles, of which 128 (representing 44
      laboratory-based outcomes) were selected. Nine were significantly associated with
      mortality, in order of decreasing scaled effect size: (1) tumor necrosis factor
      alpha, (2) hematocrit, (3) interleukin-6, (4) troponin T, (5) Kt/V(urea), (6)
      prealbumin, (7) urea reduction ratio, (8) serum albumin, and (9) C-reactive
      protein. Other oft-cited measures such as calcium phosphate product and
      parathyroid hormone were not significantly associated with mortality in pooled
      analysis. Quality improvement efforts to improve traditional laboratory-based
      outcomes in end-stage renal disease are necessary, but likely insufficient, to
      improve overall mortality in dialysis. Renewed consideration of cardiovascular,
      inflammatory, and nutritional markers that are especially strong predictors of
      mortality may have important implications for risk stratification and targeted
      therapeutic interventions.

PMID- 19583606
TI  - Etiology and management of chylothorax following pediatric heart surgery.
AB  - BACKGROUND: Chylothorax after congenital heart surgery (CHD) is a potentially
      challenging complication. The purpose of this study was to review our experience
      with the management of chylothorax following congenital heart surgery. METHODS:
      Between September 1997 and August 2006, of 1341 pediatric patients undergoing
      correction of congenital heart disease in our institution, 18 (1.3%) developed
      chylothorax postoperatively. Surgical procedures included tetralogy of Fallot
      repair in 10 patients, ventricular septal defect closure (one), atrial septal
      defect with pulmonary stenosis repair (one), Fontan procedure (three),
      coarctation of the aorta repair (one), aortopulmonary shunt (one), and ligation
      of patent ductus arteriosus in one patient. All patients followed a therapeutic
      protocol including complete drainage of chyle collection and controlled
      nutrition. Somatostatin was used adjunctively in six (33.3%) patients. Surgical
      intervention was reserved for persistent lymph leak despite maximal therapy.
      Following resolution of chylothorax, a medium-chain triglyceride diet was
      implemented for six weeks. RESULTS: There were no deaths. Fifteen patients
      (83.3%) responded to conservative therapy. Lymph leak ranged from 2.5 to 14.7
      mL/kg per day for 8 to 42 days. Three patients with persistent drainage required
      thoracotomy with pleurodesis to achieve resolution, in two of which previously
      attempted chemical pleurodesis with doxycycline proved ineffective. Duration of
      lymph leak in this subgroup ranged from 15 to 47 days with 5.1 to 7.4 mL/kg per
      day output. CONCLUSIONS: Postoperative chylothorax is an infrequent complication
      of surgery for congenital heart disease and can occur even after median
      sternotomy in the absence of pathologically elevated venous pressure or Fontan
      circulation. Although hospitalization can be prolonged, conservative therapy is
      effective in most cases, while surgical pleurodesis proved successful in the
      refractory cases.

PMID- 19583605
TI  - Phosphorylcholine-coated circuits improve preservation of platelet count and
      reduce expression of proinflammatory cytokines in CABG: a prospective randomized
      trial.
AB  - BACKGROUND: The interaction of blood with foreign artificial surfaces during
      cardiopulmonary bypass (CPB) has been recognized as a major stimulus in evoking a
      systemic inflammatory and metabolic response. Phosphorylcholine (PC) is a new
      generation coating material designed to ameliorate biocompatibility and thereby
      to reduce the detrimental interactions of CPB. We studied the effects of PC
      coated perfusion circuits on platelet function and the humoral and cellular
      response to CPB. METHODS: Thirty patients undergoing coronary artery bypass
      grafting were randomized to PC-coated (PC group, n = 15) and noncoated (control
      group, n = 15) circuit groups. Clinical data, total blood loss, and pre- and
      postoperative platelet counts were recorded and IL-6 and TNF-alpha, CD41a, CD42b,
      and CD62p were measured at induction of anesthesia, after the initiation of CPB
      and at termination of CPB. RESULTS: There was a significantly improved
      preservation of platelet count following CPB in the PC group (p = 0.028), which
      was sustained over a period of 72 hours. The use of PC-coated circuits further
      resulted in a significant attenuation of TNF-alpha and IL-6 expression (p < 0.05
      and p < 0.01); however, we were unable to detect any differences in clinical
      outcomes. CONCLUSIONS: Despite similar clinical outcome, the obvious reduction of
      cytokine expression and improved preservation of platelet count suggest superior
      biocompatibility of PC-coated circuits.

PMID- 19583607
TI  - Influence of methylprednisolone on levels of neuron-specific enolase in cardiac
      surgery: a corticosteroid derivative to decrease possible neuronal damage.
AB  - BACKGROUND: Cerebral injury is a well-known complication after cardiac surgery
      with cardiopulmonary bypass (CPB), especially in adult patients. Specific
      biochemical markers like neuron-specific enolase (NSE) and S-100beta protein were
      developed previously for early detecting neuronal damage after CPB.
      Corticosteroids are shown to reduce multisystemic deleterious effects of
      cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of
      this study is to demonstrate the decrease of serum neuron-specific enolase levels
      in patients who received corticosteroids before CPB. METHODS: Thirty patients
      scheduled for elective coronary bypass surgery were included in the study.
      Patients were divided randomly into two groups as the control group (n = 15) who
      underwent a standard coronary bypass surgery without any additional medication
      and the study group (n = 15) who received 1 gm of methylprednisolone before CPB.
      Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were
      drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation.
      RESULTS: Serum cytokine and NSE levels were significantly increased after CPB
      above their normal range in both groups. In the study group, IL-6 and NSE levels
      were significantly reduced while IL-10 levels were much higher after CPB. High
      NSE levels significantly correlated with IL-6 levels in the control group.
      CONCLUSION: The lower levels of NSE in patients who received methylprednisolone
      may suggest that corticosteroids might be useful in decreasing possible neuronal
      damage during heart surgery. However, we were not able to demonstrate an adverse
      neurological outcome.

PMID- 19583609
TI  - Quality improvement program increases early tracheal extubation rate and
      decreases pulmonary complications and resource utilization after cardiac surgery.
AB  - BACKGROUND: Early tracheal extubation is a common goal after cardiac surgery and
      may improve postoperative outcomes. Our study evaluates the impact of a quality
      improvement program (QIP) on early extubation, pulmonary complications, and
      resource utilization after cardiac surgery. METHODS: Between 2002 and 2006, 980
      patients underwent early tracheal extubation (<6 hours after surgery) and 1231
      had conventional extubation (> 6 hours after surgery, conventional group).
      Outcomes compared between the two groups included: (1) pneumonia, (2) sepsis, (3)
      intensive care unit (ICU) length of stay, (4) hospital length of stay, (5) ICU
      readmission, and (6) reintubation. Logistic regression analysis and propensity
      score adjustment were used to adjust for imbalances in the patients' preoperative
      characteristics. RESULTS: Early extubation rates were significantly increased
      with QIP (QIP 53% vs. Non-QIP 38%, p = 0.01). Early extubation was associated
      with a lower rate of (1) pneumonia (odds ratio [OR]= 0.35, 95% confidence
      intervals [CI]= 0.22-0.55, p <0.001), (2) sepsis (OR = 0.38, CI = 0.20-0.74, p
      <0.004), (3) prolonged ICU length of stay (OR = 0.42, CI = 0.35-0.50, p <0.001),
      (4) hospital length of stay (OR = 0.37, CI = 0.29-0.47, p <0.001), (5) ICU
      readmission (OR = 0.55, CI = 0.39-0.78, p <0.001), and (6) reintubation (OR =
      0.53, CI = 0.34-0.81, p <0.003) both in multivariable logistic regression
      analysis and propensity score adjustment. CONCLUSIONS: QIP and early tracheal
      extubation reduce pulmonary complications and resource utilization after cardiac
      surgery.

PMID- 19583608
TI  - Thromboelastography-based transfusion algorithm reduces blood product use after
      elective CABG: a prospective randomized study.
AB  - OBJECTIVE: Bleeding and allogeneic transfusion remain constant problems in
      cardiac surgical procedures. In this study, we aimed to test the role of a
      routine thromboelastography (TEG)-based algorithm on bleeding and transfusions in
      patients undergoing elective coronary artery bypass grafting (CABG). METHODS:
      Patients (n = 224) undergoing elective CABG with cardiopulmonary bypass were
      prospectively randomized into two groups according to transfusion strategy: in
      group 1 (clinician-directed transfusion, n = 110) need for blood transfusion was
      based on clinician's discretion and standard coagulation tests and in group 2
      (TEG algorithm group, n = 114) kaolin-activated (k) TEG-based algorithm-guided
      perioperative transfusion management. Transfusion, blood loss, and outcome data
      were recorded. RESULTS: There were no differences in consumption of packed cell
      units, blood loss, re-exploration for bleeding, and early clinical outcome
      between the groups. Patients in the TEG group had significantly lower median
      units of fresh frozen plasma and platelets compared with the other group (p =
      0.001). The median number of total allogeneic units transfused (packed cells and
      blood products) was significantly reduced in the TEG group compared with the
      other group (median 2, range 1-3 units vs. median 3, range 2-4 units,
      respectively, p = 0.001). The need for tranexamic acid was significantly
      diminished in the TEG group compared with the other group (10.3% vs. 19%,
      respectively, p = 0.007). CONCLUSION: Our results show that routine use of a kTEG
      guided algorithm reduces the consumption of blood products in patients undergoing
      elective CABG. Adopting such an algorithm into routine management of these
      patients may help to improve clinical outcome and reduce the potential risks of
      transfusion-related complications and total costs after CABG.

PMID- 19583611
TI  - External security stitch for retrograde cardioplegia cannula.
AB  - Retrograde cardioplegia catheter displacement represents a troublesome
      complication, frequently forcing the surgeon to interrupt the operative procedure
      and cannulate newly the coronary sinus. However, this maneuver is time consuming,
      often implies the loss of surgical exposure, and exposes again the coronary sinus
      to the risk of iatrogenic injuries. We describe the use of an external security
      stitch through the muscular right atrial wall to avoid the displacement of a
      retrograde cardioplegia catheter and analyze the anatomic conditions which
      predispose to this complication.

PMID- 19583610
TI  - Temporary epicardial ventricular stimulation in patients with atrial
      fibrillation: acute effects of ventricular pacing site on bypass graft flows.
AB  - OBJECTIVE: Data on coronary artery bypass grafts flows in patients with atrial
      fibrillation (AF) requiring epicardial ventricular pacing is lacking. This study
      aimed to evaluate the optimal epicardial ventricular pacing site in patients with
      AF following coronary artery bypass surgery (CABG). METHODS: In 23 consecutive
      patients (mean age = 69.2 +/- 1.9 years, gender = 62% male, ejection fraction
      [EF]= 50.4 +/- 2.1%) monoventricular stimulations (VVI) were tested with a
      constant pacing rate of 100 bpm. The impact of ventricular pacing on bypass graft
      flow (transit-time flow probe) and pulsatility index (PI) were measured after
      lead placement on the mid paraseptal region of the right (RVPS) and the left
      (LVPS) ventricle, on the right inferior wall (RVIW), and on the right ventricular
      outflow tract (RVOT). In addition, hemodynamic parameters were measured. Patients
      served as their own control. RESULTS: Comparison of all tested pacing locations
      revealed that RVOT stimulation provided the highest bypass grafts flows (59.9 +/-
      6.1 mL/min) and PI (2.2 +/- 0.1) when compared with RVPS (51.3 +/- 4.7 mL/min, PI
      = 2.6 +/- 0.2), RVIW (54.0 +/- 5.1 mL/m; PI = 2.4 +/- 0.2), and LVPS (53.1 +/-
      4.5 mL/min; PI = 2.3 +/- 0.1), respectively (p < 0.05). When analyzing patients
      according to their preoperative LV function (group I = EF > 50%; group II = EF <
      50%), higher bypass graft flows were observed with RVOT pacing in patients with
      lower EF (p = n.s.). CONCLUSIONS: Temporary RVOT pacing facilitates optimal
      bypass graft flows when compared with other ventricular pacing sites and should
      be the preferred method of temporary pacing in cardiac surgery patients with AF.
      Especially in patients with low EF following CABG, RVOT pacing may improve
      myocardial oxygen conditions for the ischemic myocardium and enhance graft
      patency in the early postoperative period.

PMID- 19583613
TI  - Repair of a recurrent pseudoaneurysm of the ascending aorta in an atomic bomb
      survivor with myelodysplastic syndrome.
AB  - The occurrence of infective aortic pseudoaneurysms tends to be intractable and
      difficult to treat. We experienced a very rare case of a recurrent infective
      pseudoaneurysm in the ascending aorta that occurred after cardiac surgery in an
      atomic bomb survivor with myelodysplastic syndrome. The pseudoaneurysm was
      successfully repaired using a femoral artery autograft with an omentopexy and the
      patient recovered well without any recurrence.

PMID- 19583612
TI  - The coronary sinus: a versatile option for pacemaker implantation during
      minimally invasive valve surgery.
AB  - A 66-year-old patient with previous mitral valve replacement underwent redo
      surgery for severe secondary tricuspid valve regurgitation. The patient presented
      with right heart failure and was pacemaker-dependent prior to surgery. Tricuspid
      valve replacement and implantation of a cardiac pacemaker lead through the
      coronary sinus were performed. The operative procedure and current literature are
      discussed.

PMID- 19583614
TI  - Combined surgical treatment in aortic type A dissection.
AB  - Acute Stanford type A aortic dissection is a fatal event that, for its high
      mortality when left untreated, requires urgent surgical intervention. The
      established treatment includes repair of the ascending aorta and various portions
      of the aortic arch, leaving the descending aorta untreated. We report the case of
      a 62-year-old man in whom a combined approach of the ascending aorta with
      surgical correction and transluminal placement of a stent in the aortic arch was
      performed.

PMID- 19583616
TI  - Compelling argument for an agitated saline bubble study prior to cardiac
      transplantation.
AB  - Cardiac transplant recipients with patent foramen ovale (PFO) are at risk for
      right-to-left shunting. Failure to identify this abnormality can have serious
      posttransplant consequences. In this article, we describe a cardiac transplant
      recipient with hypoxemia where a PFO was diagnosed postoperatively despite direct
      surgical investigation at the time of orthotopic heart transplantation (OHT).
      Transthoracic echocardiography with bubble study is relatively inexpensive,
      noninvasive, and simple and can be a useful method to identify PFO/atrial septal
      defect. Thus, authors recommend critically screening both donor and recipient
      hearts prior to OHT.

PMID- 19583615
TI  - Late dissection of pulmonary autograft treated by valve-sparing aortic root
      replacement.
AB  - Dissection of the pulmonary autograft is an extremely rare complication requiring
      emergent treatment as there is a chance of rupture and proximal aortic
      involvement. The autograft dissection can involve the aortic annulus, causing
      separation of leaflets from the annulus in addition to causing annular
      dilatation, thereby precluding resuspension of leaflets. The usual treatment in
      such cases is to perform the Bentall procedure, which involves placing a valved
      conduit (usually mechanical valve) and thereby necessitating anticoagulation.
      This report describes a case of successful valve-sparing aortic root replacement
      following the Ross procedure with dissection of autograft.

PMID- 19583617
TI  - Robotic hybrid procedure and triple-vessel disease.
AB  - A 56-year old man presented with increasing angina pectoris. Coronary angiogram
      showed a triple-vessel disease, with significant lesions on the main stem, on an
      obtuse marginal branch of the circumflex coronary artery (Cx), on the right
      coronary artery (RCA), and a proximal occlusion of the left anterior descending
      artery (LAD). A hybrid procedure was decided, with a beating heart totally
      endoscopic double vessel coronary artery bypass grafting (Double BHTECAB) on the
      LAD and the Cx, with the use of a four-arm robotic device, and a stent placement
      into the RCA in a second step. Both procedures went uneventfully, and the patient
      is fully asymptomatic 15 months after the procedure.

PMID- 19583619
TI  - A simple maneuver on sternal saw facilitates to perform curved sternal mini
      incisions like J- and C-shaped partial sternotomies.
AB  - Minimal invasive approaches, including partial J- or C-shaped sternotomies, have
      gained a worldwide acceptance in cardiac surgical practice. To increase the
      cosmetic benefit and improve the surgical exposure, the length of underlying
      partial sternotomy is usually 3 to 5 cm longer than the length of skin incision
      in most of these approaches. Using a standard sternal saw or a rotary craniotome,
      it is quite difficult to make sternal incision under subcutaneous tissue at both
      ends of skin incision. Moreover, standard sternal saws do not allow doing fine
      manipulations on sternum that may cause inadvertent sternal cutting, especially
      at the curved parts of C- or J-type partial sternotomies. We removed the blade
      protector part of a standard sternal saw. This simple maneuver enables surgeons
      to perform several challenging mini-sternotomies easily for adult cardiac
      procedures.

PMID- 19583618
TI  - Transpulmonary stenting of both pulmonary arteries with a surgical access through
      redo sternotomy.
AB  - We report the case of a four-year-old boy with pulmonary atresia (PA) and
      ventricular septal defect (VSD) associated with MAPCAs who had a complete repair
      two times. He developed 21 months later stenosis at the origin of both pulmonary
      arteries. The conventional interventional catheterization approaches were not
      available due to femoral vein thrombosis and severe transient complete
      atrioventricular block due to the manipulations to catheterize the left pulmonary
      artery. The stenoses were treated by implant of stents using a surgical access to
      the proximal portion of a Contegra valved conduit (Medtronic, Inc., Minneapolis,
      MN, USA) by sternotomy.

PMID- 19583620
TI  - Surgical treatment for epicardial metastasis of myxoid liposarcoma involving
      atrioventricular sulcus.
AB  - We report the case of a 52-year-old man who presented with a cardiac metastasis
      of myxoid liposarcoma invading the atrioventricular sulcus. The tumor was arising
      from the anterior wall of the right atrium and basal right ventricle. After
      complete resection of the tumor (14 x 7.5 x 6 cm, 279 g), the annulus had no
      strong supporting tissue because of invasion of the atrioventricular sulcus. The
      tricuspid valve was reconstructed with reinforcement of the annulus using an
      autologous pericardial strip. The defect of the right atrial wall was
      reconstructed with a pericardial patch. After the reconstruction,
      echocardiography showed grade 1 tricuspid regurgitation. Although the patient had
      a small metastasis to the lung after surgery, he is doing well after 31-month
      follow-up. We believe that it is justified to perform aggressive resection with
      annuloplasty, when it is feasible, for cardiac metastasis of myxoid liposarcoma.

PMID- 19583621
TI  - Impending aneurysm rupture after endovascular repair of infrarenal abdominal
      aortic aneurysm.
AB  - An 81-year-old male presented with lower abdominal pain radiating to back
      associated with diaphoresis. He received endovascular repair of an infrarenal
      abdominal aortic aneurysm 21 months ago. Triple phase abdominal CT showed
      impending aneurysm rupture secondary to endoleak. After re-stenting and
      percutaneous transluminal angioplasty, he had an uneventful recovery later.

PMID- 19583622
TI  - Kommerell's diverticulum, risk factor for aortic dissection.
AB  - A 54-year-old man presented with sharp chest pain and hypertension. He was
      treated with intravenous antihypertensive with good control of the blood
      pressure. Chest X-ray showed widened mediastinum, and subsequent computed
      tomography scan of the chest demonstrated dissection of the descending thoracic
      aorta. It also showed an aberrant right subclavian artery with retrograde
      extension of dissection and Kommerell's diverticulum, which is dilatation at the
      origin of the aberrant subclavian artery.

PMID- 19583623
TI  - Surgical repair of anomalous coronary arteries arising from the opposite sinus of
      Valsalva in infants and children.
AB  - BACKGROUND: Unroofing of anomalous coronary artery originating from the opposite
      sinus of Valsalva has become the procedure of choice for this congenital lesion,
      with surgery performed in children as young as two years old. An increasing
      number of this anomaly is diagnosed in infancy with no clear indication whether
      surgical repair should be done in this age group. This paper reviews our
      experience with this anomaly, and focuses on its surgical management in infants.
      METHODS: Between April 2002 and February 2007, eight patients underwent surgical
      repair of anomalous coronary artery arising from the opposite sinus of Valsalva
      and coursing between the aorta and pulmonary artery. Patients' age varied from
      two months to 28 years with a mean of 11.7 +/- 11.1 years. SURGICAL TECHNIQUE:
      Surgical repair involved unroofing the intramural segment of the anomalous
      coronary artery using cardiopulmonary bypass. RESULTS: Two patients were younger
      than one year (Group A), and six patients were older than one year (group B). The
      mean intensive care unit stay was 2.5 +/- 0.7 days for Group A and 2.8 +/- 1.9
      for Group B. The mean hospital stay was 4 +/- 1.4 days for Group A and 4.3 +/-
      2.4 days for Group B. There was no mortality and no complications. The mean
      follow-up period is 14 +/- 15.7 months with a range of one to 39 months. At the
      time of the last follow-up, all patients were asymptomatic in New York Heart
      Association class I and follow-up echocardiography on six of eight patients
      showed wide open coronary ostium. CONCLUSION: Unroofing the anomalous coronary
      artery arising from the opposite sinus of valsalva can be done in infants with
      minimal morbidity and mortality. Longer follow-up is needed to assess long-term
      results.

PMID- 19583624
TI  - Left ventricular-right atrial communication (Gerbode-type defect) following
      mitral valve replacement.
AB  - We report a case of left ventricular-right atrial communication in a 51-year-old
      patient following mitral valve replacement. Transesophageal echocardiography was
      used to make the diagnosis, and the communication was closed surgically using
      pledgeted sutures. The surgical management of such defects is discussed.

PMID- 19583625
TI  - Aortic arch aneurysm associated with arch vessel anomalies: truncus bicaroticus
      and retroesophageal right subclavian artery.
AB  - An atherosclerotic aortic arch aneurysm associated with a common origin for both
      carotid arteries is a rare condition. An aberrant right subclavian artery is just
      as rare, especially with a retroesophageal course. A combination of these two
      conditions, we believe, has never been reported.

PMID- 19583626
TI  - Autologous pericardium patch aneurysm after ventricular septal defect closure and
      arterial switch operation.
AB  - A neonate with L-transposition of the great arteries with ventricular septal
      defect underwent complete repair using fresh autologous pericardium to close the
      ventricular septal defect as well as to reconstruct the neo pulmonary artery
      sinuses. Four months later, the child came back with right ventricular inflow
      obstruction related to aneurysmal pericardial patch, severe tricuspid
      regurgitation, and severe supra-valvular pulmonic stenosis. At reoperation, there
      was a redundant, aneurysmal pericardial patch densely adherent to the septal and
      posterior leaflets of the tricuspid valve, which was damaged. The pericardial
      patch was replaced, the pulmonary artery enlarged, and tricuspid valve repaired.
      Postoperative course was uneventful, but residual moderate tricuspid
      regurgitation required intensive medical treatment.

PMID- 19583627
TI  - Diagnosis, operation, recurrence, metastasis, and death: a case of primary
      cardiac rhabdomyosarcoma.
AB  - We present a case report of a 48-year-old man with a huge left atrial
      rhabdomyosarcoma who presented as severe mitral stenosis and accepted emergency
      surgery. Two years later, a pathologic fracture revealed osseous metastasis, and
      intracardiac recurrence was detected by echocardiography. The patient died of
      multiple organ failure in the end. This case is an unusual presentation of
      complete course of cardiac rhabdomyosarcoma (CR) from diagnosis, operation,
      recurrence, and metastasis to death. Although primary CR is highly lethal,
      operation should be indicated to clarify the diagnosis, relieve symptoms, and
      improve short-term survival.

PMID- 19583628
TI  - Left ventricular epicardial hydatid cyst compressing the left circumflex artery.
AB  - Cardiac hydatid is a rare disease with varied presentation. We report a unique
      case of left ventricular epicardial hydatid cyst causing left circumflex artery
      compression. Cardiac hydatids have to be surgically treated on diagnosis because
      of the high risk of catastrophic rupture. We discuss the surgical principles and
      the other adjuncts to avoid recurrence.

PMID- 19583629
TI  - Lower blood pressure goals for cardiovascular and renal risk reduction: are they
      defensible?

PMID- 19583630
TI  - Commentary: revisiting the early morning blood pressure surge and myocardial
      ischemia.

PMID- 19583631
TI  - Early morning surge and dipping status of blood pressure: are these of predictive
      value for silent myocardial ischemia?
AB  - To investigate the predictive value of morning surge (MS) and dipping status of
      blood pressure (BP) for ST-segment depression (ST depression) in hypertensive
      persons, the combined 24-hour ambulatory BP measurement and Holter
      electrocardiographic recordings of 344 patients (132 women and 212 men, 60+/-12
      years) were analyzed. The morning BP surge was calculated as mean systolic BP
      during the 2 hours after awaking minus the mean systolic BP during the 1 hour
      that included the lowest sleep BP. Depending on the percentage decrease in
      systolic BP at night, patients were subdivided into extreme dippers, dippers,
      nondippers, and risers. ST depression was defined as horizontal or descending ST
      depression of 1 mm of 1 minute duration and a 1-minute interval after the
      previous episode or 24-hour mean ST-segment value <-0.1 mV. ST depression was
      observed in 76 (22.1%) of 344 patients. The mean MS in patients with ST
      depression was with 25+/-15 mm Hg and not significantly different when compared
      with patients without ST depression (26+/-15 mm Hg). The prevalence of ST
      depression was not significantly different in dippers, extreme dippers,
      nondippers, and risers (20%, 23.5%, 23%, and 25.5%, respectively). Systolic and
      diastolic BP values during ST depression were significantly higher in the morning
      as compared with ST depression in the evening (149/84 mm Hg vs 138/78 mm Hg,
      P<.05). In the present study, MS and dipping status of BP were not associated
      with ST depression. ST depression was, however, characterized by significantly
      higher BP peaks in the early morning hours.

PMID- 19583632
TI  - ASH Position Paper: Dietary approaches to lower blood pressure.
AB  - A substantial body of evidence has implicated several aspects of diet in the
      pathogenesis of elevated blood pressure (BP). Well-established risk factors for
      elevated BP include excess salt intake, low potassium intake, excess weight, high
      alcohol consumption, and suboptimal dietary pattern. African Americans are
      especially sensitive to the BP-raising effects of excess salt intake,
      insufficient potassium intake, and suboptimal diet. In this setting, dietary
      changes have the potential to substantially reduce racial disparities in BP and
      its consequences. In view of the age-related rise in BP in both children and
      adults, the direct, progressive relationship of BP with cardiovascular-renal
      diseases throughout the usual range of BP, and the worldwide epidemic of BP
      related disease, efforts to reduce BP in nonhypertensive as well as hypertensive
      individuals are warranted. In nonhypertensives, dietary changes can lower BP and
      delay, if not prevent, hypertension. In uncomplicated stage I hypertension,
      dietary changes serve as initial treatment before drug therapy. In hypertensive
      individuals already on drug therapy, lifestyle modifications can further lower
      BP. The current challenge is designing and implementing effective clinical and
      public health interventions that lead to sustained dietary changes among
      individuals and more broadly in the general population.

PMID- 19583633
TI  - Realities of newer beta-blockers for the management of hypertension.
AB  - Beta-blockers are prescribed for a variety of cardiovascular conditions including
      hypertension, heart failure, primary treatment of myocardial infarction (MI), and
      secondary prevention of ischemic cardiac events. Yet they remain underprescribed
      in populations at increased risk for cardiovascular disease because of
      tolerability and safety concerns. Beta-blockers are heterogeneous with respect to
      pharmacokinetic and pharmacodynamic effects. "Original" agents were nonselective,
      blocking both beta1-adrenoceptors and beta2-adrenoceptors. Later, new agents were
      developed with selectivity for beta1-adrenoceptors, and were subsequently
      followed by beta-blockers, which exhibit additional effects, such as
      vasodilation. Among newer agents, labetalol, carvedilol, and nebivolol have been
      approved for use in the United States. Nebivolol possesses both beta1-selectivity
      and nitric oxide-mediated vasodilatory effects, while carvedilol has attractive
      effects on insulin resistance and exhibits antioxidant effects. Newer beta
      blockers may overcome concerns about efficacy, adverse effects, and tolerability,
      while delivering cardiovascular protection.

PMID- 19583634
TI  - Improving outcomes in hypertensive patients: focus on adherence and persistence
      with antihypertensive therapy.
AB  - Although effective control of blood pressure (BP) reduces the risk of
      cardiovascular events in patients with hypertension, BP control rates among
      treated patients in actual clinical practice are less than optimal. Although the
      costs of medicines and medical care (which are difficult to estimate both in
      clinical trials and general clinical practice) are important, medication-taking
      behavior--adherence and persistence with antihypertensive regimens--influences BP
      control rates. Many factors affect adherence and persistence with medications,
      including efficacy and tolerability of drugs prescribed, such that rates vary
      greatly among antihypertensive classes. In general, medications with fewer
      adverse effects (in registration trials or large outcomes studies) are associated
      with increased adherence and lower discontinuation rates. More widespread use of
      such agents, particularly those available in generic formulations or in low-cost
      formularies, may lead to better long-term BP control and fewer cardiovascular
      events.

PMID- 19583635
TI  - Management of Takayasu arteritis during pregnancy.

PMID- 19583636
TI  - A new intravenous calcium channel blocker option to treat acute elevations in
      blood pressure.

PMID- 19583637
TI  - Heart failure in people younger than 50 years is more common in black than white
      Americans and is closely associated with poorly treated and controlled
      hypertension: the CARDIA study.

PMID- 19583638
TI  - Lifestyle changes and blood pressure control: a community-based cross-sectional
      survey (2006 Ontario Survey on the Prevalence and Control of Hypertension).

PMID- 19583643
TI  - The need for complementary and alternative medicine familiarisation in
      undergraduate nurse education.

PMID- 19583644
TI  - Sleep disturbance experiences among perimenopausal women in Taiwan.
AB  - AIM: To generate a descriptive theory framework regarding the experiences of
      sleep disturbances among perimenopausal women in Taiwan. BACKGROUND: Although
      studies show that some perimenopausal women are troubled by sleep problems,
      little information was found about the subjective experiences of sleep
      disturbances among these women. Research is required to explore women's feelings
      or perceptions in dealing with their sleep problems. These understandings will be
      important to help alleviate perimenopausal women's sleep problems. DESIGN: A
      grounded theory research design was applied. METHOD: Twenty-one Taiwanese sleep
      disturbed women, aged 46-57 years, participated in in-depth interviews. RESULTS:
      'Getting back a good night's sleep' was the core theme for describing and guiding
      the process of the women's sleep disturbance experiences. During the process,
      'disturbed sleep' was identified as the antecedent condition that included
      subcategories: easy awakening, difficulty falling asleep, inner worries, physical
      discomfort and genetic and bodily constitution. Analyses showed five categories
      (some with subcategories) of the sleep disturbed women: (i) worsening health
      status - physical exhaustion, impaired social interactions, emotional swings and
      decreased work performance; (ii) living with lonely nights - self-help and
      endurance; (iii) a search for resources to relieve sleep difficulties - doctor
      shopping, trying alternative therapies, exercising and seeking support; (iv)
      vicious cycle and (v) acceptance of insomnia. CONCLUSIONS: Women expected to
      relieve their sleep disturbance by finding comprehensive counselling or by their
      body constitution responding to treatment. Healthcare providers need to value
      women's individual concerns and subjective voices. Providers must seek out sleep
      counselling instead of simply prescribing drugs for their sleep difficulties.
      RELEVANCE TO CLINICAL PRACTICE: It is crucial to integrate perimenopausal sleep
      care by implementing a multidimensional approach such as sleep assessment
      laboratories, sleep counselling, complementary alternative medicine, sleep
      strategies and support groups.

PMID- 19583645
TI  - An educational intervention to improve women's ability to cope with childbirth.
AB  - AIM AND OBJECTIVE: To test the effectiveness of an efficacy-enhancing educational
      intervention to promote women's self-efficacy for childbirth and coping ability
      in reducing anxiety and pain during labour. BACKGROUND: The evidence of the
      effective application of the self-efficacy theory in health-promoting
      interventions has been well established. Little effort has been made by health
      professionals to integrate self-efficacy theory into childbirth care. DESIGN:
      Randomised controlled trial. METHODS: An efficacy-enhancing educational
      intervention based on Bandura's self-efficacy theory was evaluated. The eligible
      Chinese first-time pregnant women were randomly assigned to either an
      experimental group (n = 60) or a control group (n = 73). The experimental group
      received two 90-minute sessions of the educational programme in between the 33rd
      35th weeks of pregnancy. Follow-up assessments on outcome measures were conducted
      within 48 hours after delivery. The short form of the Chinese Childbirth Self
      Efficacy Inventory was used to measure maternal self-efficacy prior to labour.
      Evaluation of pain and anxiety during the three stages of labour and performance
      of coping behaviour during labour were measured by the Visual Analogue Scale and
      Childbirth Coping Behaviour Scale respectively. RESULTS: The experimental group
      was significantly more likely than the control group to demonstrate higher levels
      of self-efficacy for childbirth (p < 0.0001), lower perceived anxiety (p < 0.001,
      early stage and p = 0.02, middle stage) and pain (p < 0.01, early stage and p =
      0.01, middle stage) and greater performance of coping behaviour during labour (p
      < 0.01). CONCLUSIONS: The educational intervention based on Bandura's self
      efficacy theory is effective in promoting pregnant women's self-efficacy for
      childbirth and reducing their perceived pain and anxiety in the first two stages
      of labour. RELEVANCE TO CLINICAL PRACTICE: Relief of pain and anxiety is an
      important issue for both women and childbirth health professionals. The efficacy
      enhancing educational intervention should be further developed and integrated
      into childbirth educational interventions for promoting women's coping ability
      during childbirth.

PMID- 19583646
TI  - Effects of Meridian acupressure for stroke patients in Korea.
AB  - AIM: To examine the effects of Meridian acupressure on the functions of affected
      upper extremities, activity of daily living and depression for stroke patients.
      BACKGROUND: The handicaps of stroke patients necessitate multidisciplinary
      rehabilitation, which is aimed at decreasing the consequences of the illness in
      daily functions. In traditional Chinese medicine, Meridian acupressure has been
      used for rehabilitation of affected upper extremities of hemiplegia stroke
      patients in clinical practice. DESIGN: Randomised clinical trial. METHOD: Sample
      was 56 consecutive stroke patients in K Oriental hospital. Meridian acupressure
      was applied every day for 10 min per time in the experimental group (28 subjects)
      for two weeks. Routine care only was applied in the control group (28 subjects).
      Measures were a hand dynamometer for grip power, a 15-point graphic rating scale
      for pain, the distance round the index finger for oedema, electrogoniometry for
      the passive ROM of the upper extremities, the activity of daily living scale for
      activity of daily living and the six-face rating scale for depression. Data were
      collected from March 2003-September 2004. RESULTS: There were significant
      differences in functions of affected upper extremities, activity of daily living
      and depression between experimental and control group. CONCLUSIONS: Meridian
      acupressure was an effective intervention for improving the movement of the
      affected upper extremities, increasing activity of daily living and decreasing
      depression of hemiplegia stroke patients. RELEVANCE TO CLINICAL PRACTICE: Health
      professionals need to consider an array of methods including Meridian acupressure
      for the rehabilitation of stroke patients. Meridian acupressure has the potential
      as an alternative nursing intervention for multidisciplinary rehabilitation of
      stroke patients in practice.

PMID- 19583647
TI  - Soothing music can increase oxytocin levels during bed rest after open-heart
      surgery: a randomised control trial.
AB  - AIM: To evaluate the effect of bed rest with music on relaxation for patients who
      have undergone heart surgery on postoperative day one. BACKGROUND: Music
      intervention has been evaluated as an appropriate nursing intervention to reduce
      patients 'pain, stress and anxiety levels in several clinical settings, but its
      effectiveness in increasing patients' subjective and objective relaxation levels
      has not been examined. DESIGN: A randomised controlled trial. METHOD: Forty
      patients undergoing open coronary artery bypass grafting and/or aortic valve
      replacement surgery were randomly allocated to either music listening during bed
      rest (n = 20) or bed rest only (n = 20). Relaxation was assessed during bed rest
      the day after surgery by determining the plasma oxytocin, heart rate, mean
      arterial blood pressure, PaO2 SaO2 and subjective relaxation levels. RESULTS: In
      the music group, levels of oxytocin increased significantly in contrast to the
      control group for which the trend over time was negative i.e., decreasing values.
      Subjective relaxation levels increased significantly more and there were also a
      significant higher levels of PaO2 in the music group compared to the control
      group. There was no difference in mean arterial blood pressure, heart rate and
      SaO2 between the groups. CONCLUSION: Listening to music during bed rest after
      open-heart surgery has some effects on the relaxation system as regards s
      oxytocin and subjective relaxations levels. This effect seems to have a causal
      relation from the psychological (music makes patients relaxed) to the physical
      (oxytocin release). RELEVANCE TO CLINICAL PRACTICE: Music intervention should be
      offered as an integral part of the multimodal regime administered to the patients
      that have undergone cardiovascular surgery. It is a supportive source that
      increases relaxation.

PMID- 19583648
TI  - Use of folk remedies among families of children hospitalised in Taiwan.
AB  - AIMS: To describe the attitudes toward and the use of folk remedies among
      caregivers of children who were hospitalised in Taiwan. BACKGROUND: Parents
      incorporate folk remedies into the care of sick children in many cultures,
      including Taiwan. Twelve common folk remedies are commonly used in the Taiwanese
      culture for the care of sick children. DESIGN: The study employed a descriptive,
      exploratory design using survey methods. Participants were 92 caregivers
      (parents) whose children were hospitalised for at least three days in a hospital
      in the middle district of Taiwan. RESULTS: Sixty per cent of the participants
      used some form of folk remedies in the care of their hospitalised children. The
      most frequently used remedies were: spirit-calling (63%); carrying a cross or
      incense bag (47%), praying a Buddhist mantra (36%). There was a positive
      relationship between a positive attitude towards folk remedies and current use
      with children (p < 0.05). Logistic regression analysis revealed that parents'
      previous experience of using folk remedies (odds ratio = 0.272, p = 0.037), and
      parents' knowledge of the care of disease (odds ratio = 18.044, p = 0.015) were
      the strongest predictors of use of folk remedies. Almost three-fourths (73%) of
      all participants expected that health care providers would respect and not
      interfere with their use of folk remedies; 72% of parents stated that they would
      not tell healthcare providers about the use of folk remedies. CONCLUSIONS: The
      majority of the parents of hospitalised children in Taiwan can be expected to use
      folk remedies for the purpose of psychological and spiritual support during child
      hospitalised. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers need to be
      aware of the folk remedies used within various cultural groups so that culturally
      appropriate and safe care can be provided for the child and family.

PMID- 19583649
TI  - Effectiveness of applying progressive muscle relaxation technique on quality of
      life of patients with multiple sclerosis.
AB  - AIMS AND OBJECTIVES: To identify the effects of applying Progressive Muscle
      Relaxation Technique on Quality of Life of patients with multiple Sclerosis.
      BACKGROUND: In view of the growing caring options in Multiple Sclerosis,
      improvement of quality of life has become increasingly relevant as a caring
      intervention. Complementary therapies are widely used by multiple sclerosis
      patients and Progressive Muscle Relaxation Technique is a form of complementary
      therapies. DESIGN: Quasi-experimental study. METHOD: Multiple Sclerosis patients
      (n = 66) were selected with no probability sampling then assigned to experimental
      and control groups (33 patients in each group). Means of data collection
      included: Individual Information Questionnaire, SF-8 Health Survey, Self-reported
      checklist. PMRT performed for 63 sessions by experimental group during two months
      but no intervention was done for control group. Statistical analysis was done by
      SPSS software. RESULTS: Student t-test showed that there was no significant
      difference between two groups in mean scores of health-related quality of life
      before the study but this test showed a significant difference between two
      groups, one and two months after intervention (p < 0.05). anova test with
      repeated measurements showed that there is a significant difference in mean score
      of whole and dimensions of health-related quality of life between two groups in
      three times (p < 0.05). CONCLUSIONS: Although this study provides modest support
      for the effectiveness of Progressive Muscle Relaxation Technique on quality of
      life of multiple sclerosis patients, further research is required to determine
      better methods to promote quality of life of patients suffer multiple sclerosis
      and other chronic disease. RELEVANCE TO CLINICAL PRACTICE: Progressive Muscle
      Relaxation Technique is practically feasible and is associated with increase of
      life quality of multiple sclerosis patients; so that health professionals need to
      update their knowledge about complementary therapies.

PMID- 19583650
TI  - Turkish children loved distraction: using kaleidoscope to reduce perceived pain
      during venipuncture.
AB  - AIM: To assess the effect of distraction (looking through kaleidoscopes) to
      reduce perceived pain, during venipuncture in healthy school-age children.
      BACKGROUND: Distraction has been noted to be an effective method to help children
      cope with painful procedures. In the studies carried out, although it was found
      out that distraction made with different distracters reduced the pain of
      venipuncture, there is only one study confirming analgesic effect of distracters.
      DESIGN: The study was carried out as an intervention-control group design.
      METHOD: Children (n = 206), in whom venipuncture was applied in a laboratory for
      examination between the dates January-September 2006, were included in the study.
      The data were obtained by a form determining introductory features of the
      children and Wong-Baker FACES Pain Rating Scale and Visual Analogue Scale
      evaluating the pain. Descriptive statistics was used in the assessment of the
      data and t-test was used in comparisons of dependent-independent groups. RESULTS:
      Pain levels of the children according to both scales in intervention group were
      lower than those of control group. But, it was detected that the distinction
      between score averages of intervention and control group of Wong-Baker FACES Pain
      Rating Scale, not Visual Analogue Scale, was statistically significant (p <
      0.001). CONCLUSION: It was detected that the distraction made with kaleidoscope
      effectively reduced the pain related to venipuncture in healthy school children
      and that some features of the children influenced the perception of pain.
      RELEVANCE TO CLINICAL PRACTICE: Distraction with kaleidoscope is a method, which
      the nurse will be able to use for venipuncture to obtain optimal pain control. In
      addition, it is important for a nurse to know some features about the children
      for a pain free and positive experience.

PMID- 19583651
TI  - Efficacy of progressive muscle relaxation training in reducing anxiety in
      patients with acute schizophrenia.
AB  - AIM AND OBJECTIVES: The objective of this study was to examine the efficacy of
      progressive muscle relaxation training on anxiety in patients with acute
      schizophrenia. BACKGROUND: Many empirical studies have found progressive muscle
      relaxation training beneficial in reducing the psychological effects of anxiety.
      Progressive muscle relaxation training is also effective in reducing the distress
      symptoms associated with the symptomatology of schizophrenia. DESIGN: An
      experimental randomised controlled trial using repeated measures. METHOD: The
      study was designed to examine the effects of progressive muscle relaxation
      training on patients diagnosed with schizophrenia. Study participants were acute
      psychiatric inpatients in Taiwan. Eighteen patients were block randomised and
      then assigned to an experimental or control group. The experimental group
      received progressive muscle relaxation training and the control group received a
      placebo intervention. Results from the Beck anxiety inventory were compared
      between groups as a pretest before intervention, on day 11 of intervention and
      one week post-test after the intervention was completed. Changes in finger
      temperature were measured throughout the experiment. RESULTS: The degree of
      anxiety improvement was significantly higher in the progressive muscle relaxation
      training group than in the control group after progressive muscle relaxation
      training intervention (p < 0.0001) and at follow-up (p = 0.0446; the mean BAI
      score fell from 16.4 pretest to -5.8 post-test. After adjusting for the change in
      patient finger temperature, the mean change in temperature was significantly
      different between the two patient groups. The average body temperature increased
      significantly after applying the progressive muscle relaxation training to
      patients with schizophrenia. CONCLUSION: This study demonstrated that progressive
      muscle relaxation training can effectively alleviate anxiety in patients with
      schizophrenia. RELEVANCE TO CLINICAL PRACTICE: Progressive muscle relaxation
      training is potentially an effective nursing intervention in the reduction of
      anxiety in patients diagnosed with schizophrenia, depending on the quality of
      their mental status at the time of intervention. Progressive muscle relaxation
      training is a useful intervention as it is proven to reduce anxiety levels across
      a spectrum of psychiatric disorders.

PMID- 19583652
TI  - Disability and pain management methods of Taiwanese arthritic older patients.
AB  - AIM: This study aims to investigate the prevalence of disability, factors
      influencing disability and pain self-management techniques employed by older
      arthritis patients in Taiwan. BACKGROUND: Arthritis is the most common chronic
      disease in older people. It may result in pain, stiffness and joint deformity,
      which ultimately lead to disability. Understanding the factors influencing
      disability is needed to help arthritis sufferers to achieve optimal health
      status. DESIGN: A cross-sectional design was employed for this study. METHODS:
      One hundred and fifty-one older persons diagnosed with either rheumatoid
      arthritis or osteoarthritis were interviewed in the rheumatology clinics located
      in two medical centres in northern Taiwan. Six questionnaires were administered:
      Barthel Index, Instrumental Activity of Daily Living, Rapid Assessment of Disease
      Activity in Rheumatology, the Chinese version of Pain Management Inventory,
      Geriatric Depression Scale and Life Satisfaction Index. RESULTS: Disability was
      found in 11% of Taiwanese individuals diagnosed with either rheumatoid arthritis
      or osteoarthritis. Those in disability reported more severe disease activity,
      pain, depression and lower life satisfaction. Hierarchical multiple regression
      analysis revealed that 31-46% of the total variance of disability could be
      explained by age, gender, marriage, joint pain score, diagnosis, disease
      activity, depression and pain management. Patients with rheumatoid arthritis had
      significantly higher levels of disability, disease activity during the preceding
      six months, more depression and less life satisfaction than patients with
      osteoarthritis. CONCLUSION: Higher disability was explained by older age, female,
      unmarried, diagnosed with rheumatoid arthritis, more joint pain, more disease
      severity, more depression and more use of pain management strategies in arthritis
      patients. RELEVANCE TO CLINICAL PRACTICE: Nurses are urged to recognise the
      individual differences among the factors that are thought to contribute most to
      disability. An individualised, multidimensional and comprehensive treatment plan
      with informational support is essential to maximise pain management skills of
      arthritic older people to achieve improvement in pain, level of disability and
      mental health.

PMID- 19583653
TI  - Experiences of counselling in the emergency department during the waiting period:
      importance of family participation.
AB  - AIM: To describe patients' experiences of counselling, defined as information
      giving and advice by nursing staff, in the emergency department. A particular
      focus was on the waiting period and on the importance of family participation in
      counselling. BACKGROUND: Counselling is a widely studied topic in nursing. Too
      little is known about counselling in emergency departments and especially about
      participation of family members and suitability of counselling for the patient's
      life situation. DESIGN: Descriptive quantitative study. METHODS: Data were
      collected by questionnaires from patients (n = 107) visiting a hospital emergency
      department. The data were subjected to statistical analysis. RESULTS: Forty-two
      per cent of patients arrived at the emergency department with a family member:
      spouse or cohabiting partner, mother, father or daughter. Patients were fairly
      satisfied with the counselling. The presence of a family member was important to
      the majority of patients (75%). About half of the patients wanted information
      concerning their illness, condition and treatment to be given to their family
      members. Those visiting the department with a family member were more satisfied
      with counselling and felt that it promoted their participation in care.
      CONCLUSION: It is to encourage patients' family members to participate in
      counselling situations in emergency departments. However, the type of information
      passed on to family members should be carefully discussed and prepared. RELEVANCE
      TO CLINICAL PRACTICE: Patients' family members seem to be important partners in
      counselling situations. The presence of family members supports patients in the
      emergency department during the waiting period and helps them orientate in their
      situation. When family members are present, issues which patients wish to discuss
      should be carefully planned. Family presence should be encouraged in emergency
      departments.

PMID- 19583654
TI  - Inner power, physical strength and existential well-being in daily life:
      relatives' experiences of receiving soft tissue massage in palliative home care.
AB  - AIM AND OBJECTIVES: This article explores relatives' experiences of receiving
      soft tissue massage as a support supplement while caring for a dying family
      member at home. BACKGROUND: In palliative home care, relatives play an important
      role as carers to seriously ill and dying family members. To improve their
      quality of life, different support strategies are of importance. Complementary
      methods, such as soft tissue massage have become an appreciated supplement for
      these patients. However, only few studies focus on relatives experiences of
      receiving soft tissue massage as a supplemental support. DESIGN: Qualitative
      design METHOD: Nineteen relatives received soft tissue massage (hand or foot)
      nine times (25 minutes) in their homes. Open-ended semi-structured tape-recorded
      interviews were conducted once per relative after the nine times of massage,
      using qualitative content analysis. RESULTS: Soft tissue massage gave the
      relatives' feelings of 'being cared for', 'body vitality' and 'peace of mind'.
      For a while, they put worries of daily life aside as they just experienced
      'being'. During massage, it became apparent that body and mind is constituted of
      an indestructible completeness. The overarching theme was 'inner power, physical
      strength and existential well-being in their daily lives'. CONCLUSION: All
      relatives experienced soft tissue massage positively, although they were under
      considerable stress. Soft tissue massage could be an option to comfort and
      support relatives in palliative home care. RELEVANCE TO CLINICAL PRACTICE: In
      palliative nursing care, soft tissue massage could present a worthy supplement in
      supporting caring relatives.

PMID- 19583656
TI  - Commentary on Paley J (2009) Religion and the secularisation of health care.
      Journal of Clinical Nursing 18, 1963-1974.

PMID- 19583655
TI  - The impact of illness perception on adherence to therapeutic regimens of patients
      with hypertension in Taiwan.
AB  - AIMS: To examine the predictive effects of illness perception on adherence to
      therapeutic regimens of patients with hypertension. BACKGROUND: Illness
      perception is an important predictor for adherence to therapeutic regimens.
      Hypertension is asymptomatic. How the lay views, especially identity and causal
      attribution, affect the patients' adherence to therapeutic regimens need to be
      further explored. DESIGN: A cross-sectional survey. METHODS: Purposive sampling
      was conducted at the cardiovascular clinics of two teaching hospitals in central
      Taiwan. A sample of 277 patients was included in this study. Guided by the Self
      Regulation Model, a series of variables including socio-demographic variables,
      clinical variables, illness representations, identity and causes were evaluated
      for their relationships with adherence to the antihypertensive regimen and
      recommendations of self-management. RESULTS: Predictors of adherence to
      prescribed medications in the hierarchical logistic regressions were treatment
      control, risk factors and psychological attribution. In the self-management
      model, we found that symptoms experienced after a hypertension diagnosis,
      symptoms for blood pressure prediction, personal control, balance and cultural
      causal attribution were significant predictors of adherence to self-management,
      adding an additional 21% of the variance. The results of analysis of variance
      showed that those who were unsure if they had experienced symptoms after a
      hypertension diagnosis were more likely to self-regulate (increase or decrease)
      prescribed medications than those without symptoms. CONCLUSIONS: The findings
      suggest that the Self Regulation Model may provide a useful framework for
      understanding and explaining adherence to therapeutic regimens of patients with
      hypertension across cultures. RELEVANCE TO CLINICAL PRACTICE. Factors that affect
      the patients' adherence to prescribed medications and self-management
      recommendations differ greatly. Despite its subjectivity, identity showed
      significantly predictive effects on adherence to self-management. Understanding
      patients' lay views on hypertension allows health professionals providing
      effective care for better adherence to therapeutic regimens.

PMID- 19583658
TI  - Nursing on television: are we being served?

PMID- 19583659
TI  - Older people and falls: health status, quality of life, lifestyle, care networks,
      prevention and views on service use following a recent fall.
AB  - AIM AND OBJECTIVE: This study has investigated older people's experiences of a
      recent fall, its impact on their health, lifestyle, quality of life, care
      networks, prevention and their views on service use. BACKGROUND: Falls are common
      in older people and prevalence increases with age. Falls prevention is a major
      policy and service initiative. DESIGN: An exploratory, qualitative design
      involving two time points. METHOD: A convenience sample of 27 older people from
      two primary care trusts who had a recent fall. Taped semi structured qualitative
      interviews were conducted and repeated at follow up to detect change over time
      and repeat falls. Data were collected on their experience of falls, health,
      activities of living, lifestyle, quality of life, use of services, prevention of
      falls, informal care and social networks. Content analysis of transcribed
      interviews identified key themes. RESULTS: The majority of people fell indoors (n
      = 23), were repeat fallers (n = 22) with more than half alone when they fell (n =
      15). For five people it was their first ever fall. Participants in primary care
      trust 1 had a higher mean age than those in primary care trust 2 and had more
      injurious falls (n = 12, mean age 87 years vs. n = 15, mean age 81 years). The
      majority of non-injurious falls went unreported to formal services. Falls can
      result in a decline in health status, ability to undertake activities of living,
      lifestyle and quality of life. CONCLUSIONS: Local informal care and support
      networks are as important as formal care for older people at risk of falls or who
      have fallen. Access to falls prevention programmes and services is limited for
      people living in more rural communities. RELEVANCE TO PRACTICE: Falls prevention
      initiatives and services should work with local communities, agencies and
      informal carers to ensure equitable access and provision of information,
      resources and care to meet the needs of older people at risk or who have fallen.

PMID- 19583660
TI  - The meaning of feeling well in people with moderate or severe traumatic brain
      injury.
AB  - AIM: The aim of this study was to elucidate the meaning of feeling well for
      people with moderate or severe traumatic brain injury. BACKGROUND: Considerable
      attention has been given to research consequences, quality of life and
      satisfaction with life in people with traumatic brain injury. Most studies reveal
      negative aspects of living with traumatic brain injury. Knowledge that provides
      an understanding of the meaning of feeling well for people with a traumatic brain
      injury entails the possibility that they could receive support to feel well,
      despite their injury. DESIGN: This study used a qualitative research approach, as
      the aim was to elucidate meaning. METHODS: Data were collected through
      qualitative research interviews with two women and six men with moderate or
      severe traumatic brain injury who had lived with the injury for between 7-15
      years. A phenomenological hermeneutic method was used to interpret the data.
      RESULTS: The meaning of feeling well for people with moderate or severe traumatic
      brain injury was that the initially unfamiliar life with traumatic brain injury
      became familiar. This included finding strength, regaining control over everyday
      life, being close to someone and being good enough. People with traumatic brain
      injury felt well when they became reconciled with the circumstances of their life
      and created a new entity in that life, in which their complete health had been
      lost. RELEVANCE TO CLINICAL PRACTICE: This study helps professionals to enhance
      their understanding and awareness of the possibilities for people with moderate
      or severe traumatic brain injury to feel well. The study showed that people with
      traumatic brain injury needed a lot of strength to achieve this. Professionals
      can help them to feel well by getting to know them and thus find ways to support
      the person's feeling of wellbeing.

PMID- 19583661
TI  - Living with hepatitis C and treatment: the personal experiences of patients.
AB  - AIM: The purpose of the study was to explore the issues surrounding chronic
      hepatitis C, combination therapy and its impact on personal relationships to
      enhance understanding of the experiences of patients living with hepatitis C.
      This paper focuses on the experiences of the patients and their partners'
      experiences will be published separately. BACKGROUND: Patients with chronic
      hepatitis C who have active inflammatory changes on liver biopsy may undergo
      combination therapy with interferon and ribavirin. For some patients, the adverse
      effects of combination therapy are so severe that it can potentially place an
      enormous stress on personal relationships. DESIGN: The study was informed by
      Heideggerian phenomenology. METHODS: Purposive sampling and semi-structured
      interviews of five patients and their partners were conducted between 2004-2006
      in Sydney Australia, to obtain a rich description of their experiences. RESULTS:
      The findings from this study revealed that chronic hepatitis C and combination
      therapy had an enormous impact on the lives of the patients, their partners and
      families. The illness and treatment had significant physiological effects that
      had an impact on quality of life; however, the social and psychological
      consequences of living with a highly stigmatised disease with an unknown course
      and outcome cannot be underestimated. CONCLUSION: The results of this study lend
      support to the effectiveness of providing equitable services to persons diagnosed
      with chronic hepatitis C. However, additional research is needed to explore
      gender, socioeconomic, sexual-orientation, transmission, cultural, religious and
      genotype differences in this group to address their needs better. RELEVANCE TO
      CLINICAL PRACTICE: Nurses play a significant role in educating patients with
      chronic hepatitis C, advocating for them and helping them to achieve a reasonable
      state of well being. Through deeper understanding of their experiences of illness
      and treatment, nurses can move beyond the medical oriented approach to care.

PMID- 19583662
TI  - Perceived control and involvement in self care in patients with colorectal
      cancer.
AB  - AIM: This paper reports the qualitative findings from a mixed methods study which
      explored patients' understandings of perceived control in relation to their self
      care during chemotherapy for colorectal cancer. BACKGROUND: A greater degree of
      patient involvement in self care is increasingly being encouraged; however,
      little is known about how factors such as perceived control influence patients'
      active involvement in self care. DESIGN: Qualitative, longitudinal study.
      METHODS: Semi structured interviews were conducted with 11 patients before and
      after six months of chemotherapy treatment for colorectal cancer in a Scottish
      cancer centre between March 2005-June 2006. The interviews, conducted as part of
      a larger study, explored patients' understandings of their perceived control over
      managing treatment-related side effects and how this influenced their attitudes
      toward, and role preferences in, self care. RESULTS: Patients fell into one of
      two groups: 'high' or 'low' perceived controllers. High-perceived controllers
      were more likely to view their active involvement in self care positively, as
      being necessary in managing treatment-related effects and were less likely to
      rely on nurses to take overall responsibility for the management of treatment
      related side effects. Low-perceived controllers were less likely to believe in
      the importance or necessity of their active involvement in self care and more
      likely to perceive nurses as being the ones responsible for the management of
      treatment-related side effects. CONCLUSIONS: Perceived control during treatment
      for cancer influences patients' perceptions toward, and role preferences in, self
      care. RELEVANCE TO CLINICAL PRACTICE: Clinical interventions designed to enhance
      involvement in self care would benefit from focussing on enhancing patients'
      perceived control and understanding their role preferences in self care. Patients
      with different understandings of perceived control may require different help and
      support to encourage their involvement in self care.

PMID- 19583663
TI  - Anxiety in the operating theatre: a study of frequency and environmental impact
      in patients having local, plexus or regional anaesthesia.
AB  - AIMS: To estimate the frequency of intraoperative anxiety, the influence of
      environmental factors on intraoperative anxiety and to study the relationship
      between intraoperative anxiety and generalised anxiety and depression.
      BACKGROUND: Previous research has documented that surgery is associated with
      increased stress and anxiety, which have an adverse effect on patient outcomes.
      Few studies have been conducted to obtain patients' perspectives about the
      influence of the operating theatre environment on anxiety. DESIGN: The study used
      a survey design including questionnaires. METHOD: Clinical variables were noted
      from the anaesthesia medical records. The sample (n = 119) comprised patients
      undergoing elective surgery and emergency operations within 24 hours of
      admission. Anxiety was assessed by the Jakobsen's questionnaire and the Hospital
      Anxiety and Depression scale. RESULTS: Twenty-three per cent felt anxious on
      arrival at the operating theatre, 35% were anxious at induction of anaesthesia,
      while 12% felt anxious after induction. At start of surgery 15% experienced
      anxiety and during surgery 9% were anxious. Continuous information reduced the
      experience of anxiety in 49% of the patients and the opportunity to ask questions
      during the intraoperative period reduced anxiety in 55%. The sight of technical
      equipment and surgical instruments was reported to increase anxiety in 9% and 6%
      of the sample, respectively. Patients with higher levels of general anxiety and
      depression also experienced significantly higher levels of anxiety in the
      intraoperative period. CONCLUSIONS: In this study patients experience highest
      level of anxiety at induction of anaesthetics. The operating theatre environments
      impact on patients' anxiety are in less degree influenced by the sight and
      hearing of the technical equipment and the surroundings. Continuous information
      and opportunity to ask questions reduces patients' anxiety. Results indicate that
      there is a significant positive relationship between generalised anxiety and
      depression prior to admission and anxiety experienced during the intraoperative
      period. RELEVANCE TO CLINICAL PRACTICE: Generalised anxiety and depression prior
      to surgery should be identified to implement nursing interventions to reduce
      anxiety in the operating theatre.

PMID- 19583664
TI  - Health literacy and functional health status in Korean older adults.
AB  - AIMS AND OBJECTIVES: The aim of the study was to investigate the relationships of
      health literacy to chronic medical conditions and the functional health status
      among community-dwelling Korean older adults. BACKGROUND: In the literature,
      limited health literacy has been reported to have adverse effect on health
      outcomes. However, the link between health literacy to health status among Korean
      older adults needs to be clarified. DESIGN: A cross-sectional survey. METHODS: A
      cross-sectional survey of 103 community-dwelling Korean older adults was
      conducted from June 2007-September 2007. Health literacy was measured using the
      Korean Functional Health Literacy test and functional health status was measured
      using the subscales of the Medical Outcomes Study 12-item Short-Form Health
      Survey. RESULTS: Individuals with a low health literacy had significantly higher
      rates of arthritis and hypertension. After adjusting for age, education and
      income, older individuals with low health literacy had higher limitations in
      activity and lower subjective health. In a model adjusting for age and income
      only, older individuals with low health literacy were more likely to report lower
      levels of physical function and subjective health and higher levels of
      limitations in activity and pain. CONCLUSIONS: Among community-dwelling Korean
      older adults, limited health literacy is associated independently with higher
      rates of chronic medical conditions and lower subjective health status. RELEVANCE
      TO CLINICAL PRACTICE: Nurses are key to providing health education to older
      adults. The understanding of the relationship of health literacy to health status
      is essential to develop communication and health education efforts for older
      adults in nursing practice.

PMID- 19583665
TI  - Investigating factors associated with nurses' attitudes towards perinatal
      bereavement care: a study in Shandong and Hong Kong.
AB  - AIMS: To explore nurses' attitudes towards perinatal bereavement care and to
      identify factors associated with these attitudes. BACKGROUND: It is likely that
      the attitude of nursing staff can influence recovery from a pregnancy loss and
      that nurses with positive attitudes to bereavement care can help bereaved parents
      to cope during their grieving period. DESIGN: Survey. METHOD: Data were collected
      through a structured questionnaire; 657 nurses were recruited from Obstetrics and
      Gynaecology units in Hong Kong and Shandong during 2006. Outcome measures
      included attitudes towards perinatal bereavement care, importance of hospital
      policy and training support for bereavement care. RESULTS: The majority of nurses
      in this study had a positive attitude to bereavement care. Results show that only
      21.6% (n = 141) of the nurses surveyed had bereavement-related training. In
      contrast, about 89.8% (n = 300) believed they needed to be equipped with relevant
      knowledge, skills and understanding in the care and support of bereaved parents
      and more than 88.5% (n = 592) would share their experiences with their colleagues
      and seek support when feeling under stress. A regression model showed that age,
      past experience in handling grieving parents, recent ranking and nurses'
      perceived attitudes to hospital policy and training provided for bereavement care
      were the factors associated with nurses' attitudes to perinatal bereavement care.
      CONCLUSIONS: Nurses in both cities emphasised their need for increased knowledge
      and experience, improved communication skills and greater support from team
      members and the hospital for perinatal bereavement care. RELEVANCE TO CLINICAL
      PRACTICE: These findings may be used by nursing educators to educate their
      students on issues related to delivery of sensitive bereavement care in perinatal
      settings and to enhance nursing school curricula.

PMID- 19583666
TI  - Staff acceptance of video monitoring for coordination: a video system to support
      perioperative situation awareness.
AB  - AIM: To understand staff acceptance of a remote video monitoring system for
      operating room (OR) coordination. BACKGROUND: Improved real-time remote visual
      access to OR may enhance situational awareness but also raises privacy concerns
      for patients and staff. DESIGN: Survey. METHODS: A system was implemented in a
      six-room surgical suite to display OR monitoring video at an access restricted
      control desk area. Image quality was manipulated to improve staff acceptance. Two
      months after installation, interviews and a survey were conducted on staff
      acceptance of video monitoring. RESULTS: About half of all OR personnel responded
      (n = 63). Overall levels of concerns were low, with 53% rated no concerns and 42%
      little concern. Top two reported uses of the video were to see if cases are
      finished and to see if a room is ready. Viewing the video monitoring system as
      useful did not reduce levels of concern. Staff in supervisory positions perceived
      less concern about the system's impact on privacy than did those supervised (p <
      0.03). Concerns for patient privacy correlated with concerns for staff privacy
      and performance monitoring. Technical means such as manipulating image quality
      helped staff acceptance. CONCLUSIONS: Manipulation of image quality resulted
      overall acceptance of monitoring video, with residual levels of concerns. OR
      nurses may express staff privacy concern in the form of concerns over patient
      privacy. RELEVANCE TO CLINICAL PRACTICE: This study provided suggestions for
      technological and implementation strategies of video monitoring for coordination
      use in OR. Deployment of communication technology and integration of clinical
      information will likely raise concerns over staff privacy and performance
      monitoring. The potential gain of increased information access may be offset by
      negative impact of a sense of loss of autonomy.

PMID- 19583667
TI  - Nursing students' knowledge, attitude and readiness to work for clients with
      sexual health concerns.
AB  - AIMS: To investigate nursing students' knowledge, attitude and readiness to work
      for clients with sexual health concerns and to identify strategies to help
      students develop as they take up their role in sexual health-related care.
      BACKGROUND: There is an increasing global demand for improving sexual health. A
      better understanding of nursing students' attitude and readiness to work for
      clients with sexual health concerns is the beginning of this endeavour. The need
      to explore strategies for developing competent health care practitioners is
      timely. DESIGN: A cross-sectional survey. METHODS: Nursing students (n = 377)
      studying in pre- and post-registration programmes were surveyed at a university
      in Hong Kong using a questionnaire with open- and closed-ended questions about
      their knowledge, attitude and self-perception on readiness to work for clients
      with sexual health concerns. RESULTS: Students' knowledge of sexual health was
      satisfactory. They were positive in acknowledging the nursing role in sexual
      health care, but hesitant in taking up an active role in practice. Students'
      readiness to participate in related activities was below satisfactory. Their
      perception of inadequate knowledge, feelings of anxiety, worries about
      colleagues' and clients' possible adverse responses and inadequate exemplars were
      major factors affecting their readiness. This paper also highlighted some
      important learning areas and strategies that could help in enhancing students'
      knowledge and confidence in sexual health care practices. CONCLUSION: Improving
      the educational programme and clinical practice for nursing students is necessary
      but may not be adequate. Valuing the affective aspect of education, formal
      recognition of this extended role and advancing related education to a post
      experience level would also benefit the development of sexual health care.
      RELEVANCE TO CLINICAL PRACTICE: Preparing more mentors as exemplars, inviting
      clinicians and managers as partners in sexual health-related care would help
      nursing students to work efficiently for clients with sexual health concerns.

PMID- 19583668
TI  - Staff attitudes towards institutionalised dementia residents.
AB  - AIM: To explore the attitudes of staff caring for institutionalised dementia
      residents and the variables associated with these attitudes. METHODS: Fourteen
      nursing homes and one hospital-based geriatric ward in Bergen, Norway were
      surveyed, using the translation of an Approach to Dementia Questionnaire. The
      study population (n = 291) was a mixture of registered nurses, auxiliary nurses,
      nursing assistants and non-trained aides. DESIGN: Survey. RESULTS: Significant
      differences in hope and person-centred attitudes were identified in this study.
      Nursing assistants, compared with registered nurses (p = 0.02), had significantly
      lower hope attitudes. Staff over 50 years of age reported significantly lower
      hope attitudes (p = 0.01) than those under 40 years of age. Staff with 10 and
      fewer years of work experience reported significantly lower hope attitudes (p =
      0.02) than those with more than 10 years of experience. Nurses with specialised
      training in geriatrics, psychiatry or dementia care had significantly higher hope
      attitudes, compared with nurses without any special training (p = 0.04). The
      person-centred attitude was lower among participants who were over 50 years old,
      compared with their counterparts under the age of 40 (p < or = 0.01). DISCUSSION:
      Education, age, work experience, care unit size and specialised training are
      associated with differences in attitudes. We recommend that employers be
      proactive in encouraging and facilitating staff development by offering further
      training that aims to impart more positive attitudes. RELEVANCE TO CLINICAL
      PRACTICE: Improvements in staff competency levels will be more important in the
      future, as a result of the forecasted increase in the percentage of the
      population who will suffer from dementia and reside in nursing homes.

PMID- 19583669
TI  - Appropriate prescribing in the elderly: an investigation of two screening tools,
      Beers criteria considering diagnosis and independent of diagnosis and improved
      prescribing in the elderly tool to identify inappropriate use of medicines in the
      elderly in primary care in Ireland.
AB  - BACKGROUND: Elderly patients are particularly vulnerable to inappropriate
      prescribing, with increased risk of adverse drug reactions and consequently
      higher rates of morbidity and mortality. A large proportion of inappropriate
      prescribing is preventable by adherence to prescribing guidelines, suitable
      monitoring and regular medication review. As a result, screening tools have been
      developed to help clinicians improve their prescribing. OBJECTIVES: To compare
      identification rates of inappropriate prescribing in elderly patients in primary
      care using two validated screening tools: Beers' criteria and improved
      prescribing in the elderly tool (IPET); to calculate the net ingredient cost
      (NIC) per month (euro) of the potentially inappropriate medicines in this
      population of patients. METHOD: A consecutive cohort of 500 patients 65 years of
      age and over were recruited prospectively from primary care over a 6 month period
      in a provincial town in Ireland. Patients' medical records (electronic and paper)
      were screened and all relevant information concerning current illnesses and
      medications was recorded on a standardized data collection form to which Beers'
      criteria [considering diagnosis (CD) and independent of diagnosis (ID)] and IPET
      tools were applied. The NIC was calculated from an edition of the Irish monthly
      index of medical specialities published concurrently with the data collection.
      RESULTS: Beers' criteria identified a total of 69 medicines that were prescribed
      inappropriately (eight CD and 61 ID) in 65 patients (13%), costing euro824.88 per
      month while IPET identified 63 potentially inappropriate medicines in 52 (10.4%)
      patients costing euro381.28 per month. CONCLUSIONS: Potentially inappropriate
      medications are prescribed in a significant proportion of elderly people in
      primary care, with significant economic implications.

PMID- 19583670
TI  - Potentially severe drug interactions in elderly outpatients: results of an
      observational study of an administrative prescription database.
AB  - PURPOSE: To estimate the prevalence of potentially severe drug-drug interactions
      (DDIs) and their relationship with age, sex and number of prescribed drugs.
      METHODS: We analysed all prescriptions dispensed from 1 January 2003 to 31
      December 2003 to individuals aged 65 or more registered under the Local Health
      Authority of Lecco, a northern Italian province with a population of almost 330
      000 persons. Elderly who received at least two co-administered prescriptions were
      selected to assess the presence of DDIs. RESULTS: The prevalence of potentially
      severe DDIs was 16%, and rose with increasing patient's age and number of drugs
      prescribed. At multivariate analysis, the adjusted odds ratios rose from 1.07
      (95% CI 1.03-1.11) in patients aged 70-74 to 1.52 (95% CI 1.46-1.60) in those
      aged 85 or older. Elderly taking more than five drugs on a chronic basis had a
      statistically significant higher risk of sever DDIs than those receiving less
      than 3 or 3-5 such drugs. CONCLUSIONS: The elderly constitutes a population at
      high risk of DDIs. As physicians still have some difficulty in managing this
      problem, it is essential to highlight for them, which factors raise the risk of
      DDIs.

PMID- 19583671
TI  - Prescribed medications and pharmacy interventions for acute respiratory tract
      infections in Swiss primary care.
AB  - BACKGROUND AND OBJECTIVES: Symptomatic medications are often not considered in
      clinical studies assessing interventions to reduce prescribing of antibiotics for
      acute respiratory tract infections (ARTI). Our study objectives were to examine
      prescribing patterns of antibiotics and symptomatic medications for ARTI in Swiss
      primary care and to monitor pharmacists' interventions during the prescription
      dispensing process. METHODS: Medical records of 695 patients participating in a
      clinical trial which was designed to reduce use of antibiotics for ARTI in
      primary care, were linked to their prescriptions. Matching of prescribed and
      dispensed medications enabled the assessment of interventions by community
      pharmacists. RESULTS: On average, 2.4 different drugs were prescribed per patient
      (in total 142 antibiotics, 1599 symptomatic medications, and 56 non-ARTI
      medication). Most patients (80%) were treated only with symptomatic medications.
      Most frequently prescribed symptomatic ARTI-medications were nasal decongestants
      (39%), cough suppressants (36%), and mucolytics (31%). Patients with prescribed
      antibiotics received significantly fewer symptomatic medications (odds ratio,
      0.24; 95% confidence interval 0.16-0.37). Over 20% of prescriptions prompted at
      least one intervention by a pharmacist in the dispensing process. A discrepancy
      between prescribed and dispensed medications was seen in 19% of patients.
      CONCLUSIONS: Prescription rates of antibiotics for ARTI in this trial were low
      and patients were treated mainly with non-antibiotic symptomatic medications.
      Efforts to reduce antibiotic prescribing may induce higher rates of use of
      medications for intensive symptomatic treatment. Considerable differences between
      prescribed and dispensed medications were noted.

PMID- 19583672
TI  - Attitudes of Australian pharmacists towards practice-based research.
AB  - BACKGROUND AND OBJECTIVE: The aim was to conduct a national cross-sectional
      survey of randomly selected Australian pharmacists to determine their attitudes
      towards and involvement in pharmacy practice research. This included the
      canvassing of perceived barriers and potential solutions to promote research
      activity in pharmacy practice. METHODS: A questionnaire was developed around
      those used in UK and Australasian studies of general practitioners' attitudes
      towards research. Questions assessed attitudes to research, involvement in
      research, barriers and facilitators to involvement, self-assessed understanding
      of research terminology, and access to and use of electronic bibliographic
      databases. One thousand pharmacists were randomly and proportionately selected
      from the State and Territory Pharmacy Board registers to receive the anonymous
      questionnaire by mail. Non-respondents were sent a follow-up reminder and second
      copy of the questionnaire after 3 weeks. RESULTS: A response rate of 37% was
      achieved. Approximately, one-third of responding pharmacists were presently, or
      had been, involved in research activities, and generally reported positive
      experiences. Lack of time and never being approached or not being aware of the
      opportunities were major barriers to pharmacist participation in research.
      Approximately, one-third of the pharmacists were not interested in participating
      in research. There was low usage of publicly available electronic bibliographic
      databases and of scientific journals. Although there was overwhelming recognition
      of the value of research to the profession, few pharmacists possessed a good
      understanding of key terms related to research and evidence-based practice (e.g.
      P-value or number needed to treat). CONCLUSION: There was overwhelming
      recognition of the value of research to the pharmacy profession. Important
      factors encouraging individual pharmacists to participate in research were a
      desire to improve the profession, the opportunity to learn more about disease
      management and to provide enhanced services to patients, and personal interest.

PMID- 19583673
TI  - Clinical impact of a pharmacist-physician co-managed programme on hyperlipidaemia
      management in Hong Kong.
AB  - OBJECTIVE: The study aimed to investigate the clinical impact of pharmacist
      physician co-managed programme on the management of hyperlipidaemia. METHODS: The
      study was a prospective randomized controlled trial. Adult patients were selected
      if: (i) they were taking one or more lipid-lowering agents with a valid lipid
      panel before their next follow up; (ii) had a baseline lipid profile within the
      previous 6 months; (iii) their lipid panel did not reach the targeted low-density
      lipoprotein-cholesterol (LDL-C) goal based on the National Cholesterol Education
      Programme Adult Treatment Panel III. Pharmacists interviewed patients in the
      intervention group for 15-30 min to provide consultation on the drug regimen and
      lifestyle modifications. A telephone follow-up every 4 weeks and a follow-up
      interview on the date of the physician visit were scheduled. Patients in the
      control group received routine conventional care. The primary outcome measurement
      was the change in lipid panel between baseline and at the end of study. RESULTS:
      One hundred and eighteen patients were recruited to the study [58 patients in
      intervention group (mean age 63 +/- 10 years old) and 60 in control group (mean
      age 61 +/- 12 years old)]. Starting with similar baseline levels, the end of
      study LDL-C and total cholesterol levels for the intervention and control groups
      were LDL-C: 2.80 +/- 0.89 mmol/L and total cholesterol 4.75 +/- 1.08 mmol/L vs.
      LDL-C: 3.24 +/- 0.78 mmol/L and total cholesterol 5.18 +/- 0.93 mmol/L,
      respectively. The differences were statistically significant (P < 0.0015).
      CONCLUSION: The study showed that a pharmacist-physician co-managed programme for
      hyperlipidaemic patient was effective in getting more patients to reach their
      target lipid levels.

PMID- 19583674
TI  - Poor applicability of estimation method for adults to calculate unbound serum
      concentrations of valproic acid in epileptic neonates and infants.
AB  - OBJECTIVE: To characterize the relationship between total and unbound
      concentrations of valproic acid (VPA) in epileptic neonates and infants, the
      clinical examination records of those patients archived via therapeutic drug
      monitoring (TDM) activities were retrospectively analyzed. METHODS: The screening
      encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were
      treated with VPA monotherapy and whose total and unbound VPA concentrations were
      determined. These data were divided into groups according to the patients' age.
      In each group, the relationship between total and unbound VPA concentrations was
      compared to a reference profile, and the deviation from the reference was
      evaluated. The reference profile was calculated using the Langmuir equation, in
      which two parameters Kd and Bm were set to 7.8 and 130 microg/mL, respectively,
      according to our previous findings. RESULTS: The relationship between total and
      unbound VPA concentrations of patients of 0 years old considerably deviated from
      the reference, and their unbound VPA concentrations were generally higher
      compared to the corresponding reference values. It is suggested that the large
      deviation is related to the fact that the serum albumin concentrations of
      patients younger than 1 year old tend to be lower than those of patients in other
      age groups. CONCLUSION: Since the relationship between the VPA concentrations of
      epileptic neonates and infants is noticeably different from the reference, the
      unbound serum VPA concentrations of these patients are not adequately estimated
      using the same method as that for grown-ups. The unbound VPA concentrations of
      neonates and infants should be explicitly determined via TDM activities.

PMID- 19583675
TI  - Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5%
      dextrose stored on polyolefin infusion bags.
AB  - BACKGROUND: Calcium levofolinate infusions could be prepared in advance by a
      centralized intravenous additive service (CIVAS) to improve safety and time
      management. OBJECTIVE: To investigate the effect of freezing, microwave thawing
      and long-term storage at 5 +/- 3 degrees C on the stability of calcium
      levofolinate in 5% dextrose solution. METHODS: Solutions of 250 mL of 5% dextrose
      in polyolefin bags (n = 5) containing approximately 400 mg of calcium
      levofolinate were prepared under aseptic conditions and frozen for 95 days at -20
      degrees C. The solutions were then thawed using microwaves and stored at 5 +/- 3
      degrees C for 1 month. The calcium levofolinate concentrations were measured by
      high performance liquid chromatography (HPLC). Visual inspection was performed
      and pH was measured periodically during the storage at 5 +/- 3 degrees C.
      Stability of the solution was defined as a concentration remaining superior to
      90% of the initial concentration by regression analysis as recommended by the
      Food and Drug Administration (FDA). RESULTS: No colour change or precipitation in
      the solutions was observed. Calcium levofolinate infusions were stable when
      stored at 5 +/- 3 degrees C during 1 month after freeze-thaw treatment.
      Throughout this period, the lower confidence limit of the estimated regression
      line of concentration-time profile remained above 90% of the initial
      concentration. Slight change in pH values from 6.52 +/- 0.01 to 6.50 +/- 0.01
      during storage time did not affect retention time on HPLC and has no clinical
      consequence, the solutions remaining in the acceptable range for perfusion (4
      <or= pH <or= 10). CONCLUSION: Under the conditions of this study, calcium
      levofolinate in 5% dextrose infusion may be prepared, frozen in advance by CIVAS,
      and then microwave thawed before use. Such treatment extends long-term stability
      and releases pharmacist's time for major activities such as checking medication
      order errors.

PMID- 19583676
TI  - Comparison of linkage disequilibrium patterns and haplotype structure of eight
      single nucleotide polymorphisms across the CYP1A2 gene between the Korean, and
      other populations registered in the International HapMap database.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine the frequencies
      of CYP1A2 gene polymorphisms, analyze Linkage disequilibrium (LD) blocks and
      haplotypes in a Korean population, and compare them with those in African,
      European, Japanese and Chinese populations. METHODS: We searched across diverse
      studies conducted in Korea and the Knowledge Base for Korean Pharmacogenomics
      Research Network operated by Seoul National University to determine the frequency
      of single nucleotide polymorphisms (SNPs) of the CYP1A2 gene and to choose
      frequently occurring SNPs in a Korean population. We analyzed and confirmed the
      frequencies of CYP1A2 SNPs that are inferred as MAF >0.05 in 400 healthy Korean
      subjects, using direct sequencing and a TaqMan assay. The LD block and haplotypes
      were constructed from the SNP databases in the other races registered in the
      International HapMap (Europeans, Chinese, Japanese and Africans) and the
      haplotype frequencies in each race were compared with those in the Korean
      population. RESULTS AND DISCUSSION: We found 12 SNPs with minor allele frequency
      (MAF) values above 5% in the 5' regulatory regions, the exon, and surrounding
      introns of CYP1A2 gene based on previous reports in Koreans. In this study, two
      of twelve SNPs were lower than 5% in frequency (n = 400). The CYP1A2 haplotypes
      were analyzed based on 10 SNPs, confirmed to have MAF >0.05 in this study. Four
      haplotypes (H1, H2, H3 and H4) represented most of the Korean population (>94%).
      CONCLUSIONS: The haplotype frequencies among the five ethnic groups revealed that
      haplotype distributions in Koreans were similar to those of the Japanese and
      Chinese, but were quite different to those of the Africans and Europeans. These
      LD and haplotype data should be useful in drug development and in understanding
      genetic associations of CYP1A2 with adverse drug effects. These inter-ethnic
      differences in frequencies of SNPs and haplotypes may help to explain
      inconsistencies that have been reported in association studies and could
      contribute to predict the pharmacokinetics and pharmacodynamics of drugs that are
      metabolized by CYP1A2.

PMID- 19583677
TI  - CYP2C19 haplotypes in Koreans as a marker of enzyme activity evaluated with
      omeprazole.
AB  - BACKGROUND AND OBJECTIVE: CYP2C19 is clinically important in Korea because of the
      relatively high incidence of poor metabolizers in the population. To fully
      understand the genetic mechanism of the CYP2C19 defect in poor metabolizers, all
      variants need to be studied simultaneously. The aim of this study was to
      investigate the usefulness of CYP2C19 haplotypes as a marker of CYP2C19 enzyme
      activity in Koreans. METHODS: We analysed the single nucleotide polymorphisms and
      haplotypes of the CYP2C19 gene in 150 healthy Koreans and found three major
      (frequency > 0.1) haplotypes (H1, H2 and H3). One oral dose of 40 mg omeprazole
      (Losec) was administered to 30 subjects grouped as H1/H1, H2/H2, H1/H2, H1/H3 and
      H2/H3. The pharmacokinetics of omeprazole and its metabolites, 5
      hydroxyomeprazole and omeprazole sulphone, in those groups was analysed. RESULTS
      AND DISCUSSION: The area under the plasma concentration-time curve (AUC(0-
      >infinity)) and elimination half-life (T(1/2)) of omeprazole were significantly
      greater in the H2/H2 and H2/H3 groups than in the H1/H1 group (P < 0.05), whereas
      the metabolic ratios of omeprazole to 5-hydroxyomeprazole were also markedly
      higher. CONCLUSION: Although a specific SNP of CYP2C19 may be predictive of
      enzyme activity, haplotyping is more reliable for identifying poor metabolizers
      in populations with variant alleles other than CYP2C19*2 and *3 alleles.

PMID- 19583678
TI  - Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS
      patients and PAFAH genotype.
AB  - BACKGROUND: Platelet activating factor (PAF), a pro-inflammatory phospholipid,
      stimulates cytokine secretion from polymorphonuclear leukocytes expressing the
      transmembrane G-protein coupled PAF receptor. Elevated PAF levels are associated
      with acute respiratory distress syndrome (ARDS) and sepsis severity. The pro
      inflammatory effects of PAF are terminated by PAF acetylhydrolase (PAF-AH).
      OBJECTIVE: We sought to determine whether allelic variants in the human PAFAH
      gene (Arg92His, Ile198Thr, and Ala379Val) contribute to variability in PAF-AH
      activity in patient plasma obtained within 72 h of ARDS diagnosis. RESULTS:
      Plasma PAF-AH activity (mean +/- SD) was higher in patients homozygous for the
      Arg92 allele compared to His92 allele carriers (2.21 +/- 0.77 vs. 1.64 +/- 0.68
      U/min; P < 0.01; n = 31 and 21 respectively). Baseline plasma PAF-AH activity was
      higher among day 7 survivors vs. day 7 non-survivors (2.05 +/- 0.75 vs. 1.27 +/-
      0.63, P = 0.05). CONCLUSION: These data demonstrate an association between PAF-AH
      allelic variation, plasma activity, and outcome in ARDS.

PMID- 19583679
TI  - Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin
      converting enzyme inhibitor-induced cough.
AB  - BACKGROUND AND OBJECTIVE: Treatment with angiotensin-converting enzyme (ACE)
      inhibitors can induce chronic cough in many patients. Genetic variations in the
      neurokinin 2 receptor gene (NK2R) are significantly associated with cough
      sensitivity to capsaicin. METHODS: This study assessed the relationship between
      genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking
      ACE inhibitors. Patients included in the study did not have chest abnormalities,
      postnasal drip, gastroesophageal reflux or a recent history of upper respiratory
      infection. RESULTS: We detected two single nucleotide polymorphisms in the NK2R
      gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231
      were 36.3% for Gly/Gly, 49.5% for Gly/Glu and 14.3% for Glu/Glu. The allelic
      frequencies at amino acid 375 were 74.7% for Arg/Arg, 24.2% for Arg/His and 1.1%
      for His/His. The prevalence of chronic cough in patients with the amino acid 231
      genotype was 33.3% in Gly/Gly homozygotes, 24.4% in Gly/Glu heterozygotes and 0%
      in Glu/Glu homozygotes. There was a statistically significant association between
      chronic cough and the Glu/Glu allele (P = 0.028) when the data were analyzed with
      a recessive model. In addition, there was a significant inverse linear
      association between the number of Glu231 alleles and ACE inhibitor-related cough
      (P = 0.026). The prevalence of chronic cough in patients with the amino acid 375
      genotype was 22.1% in Arg/Arg homozygotes, 31.8% in Arg/His heterozygotes and 0%
      in His/His homozygotes, although none of these association were statistically
      significant. CONCLUSION: Our findings indicate that the Gly231Glu polymorphism is
      associated with a lower prevalence of ACE inhibitor-related cough.

PMID- 19583680
TI  - Effect of various estimates of renal function on prediction of vancomycin
      concentration by the population mean and Bayesian methods.
AB  - OBJECTIVE: Renal function was estimated in 129 elderly patients with methicillin
      resistant Staphylococcus aureus (MRSA) who were treated with vancomycin (VCM).
      The estimation was performed by substituting serum creatinine (SCR) measured
      enzymatically and a value converted using the Jaffe method into the Cockcroft
      Gault and Modification of Diet in Renal Disease (MDRD) equations. The serum
      trough level was predicted from three estimates of renal function by the
      population mean (PM) and Bayesian methods and the predictability was assessed.
      METHODS: Two-compartment model-based Japanese population parameters for VCM were
      used, and the mean prediction error (ME) and root mean squared error (RMSE) were
      calculated as indices of bias and accuracy, respectively, for predictions by the
      PM and Bayesian methods. RESULTS: The PM method gave the highest correlation with
      the measured value using the estimate of renal function obtained by substituting
      the Jaffe-converted SCR into the Cockcroft-Gault equation. There was no positive
      or negative bias in the ME and the value was significantly smaller than for other
      predicted data (P < 0.05). RMSE was also the smallest, indicating that this
      method increases the predictability of the serum VCM trough level. While, ME
      showed a negative bias for all values predicted by the Bayesian method, both the
      ME and RMSE were very small. CONCLUSION: In the application of the PM method for
      VCM treatment of elderly patients with MRSA, substitution of SCR based on the
      Jaffe method into the Cockcroft-Gault equation increases the predictability of
      the serum VCM trough level. The Bayesian method predicted the serum VCM trough
      level with high accuracy using any of the estimates of renal function.

PMID- 19583681
TI  - Population pharmacokinetic analysis of vancomycin in patients with gram-positive
      infections and the influence of infectious disease type.
AB  - OBJECTIVE: To describe the population pharmacokinetics of vancomycin in patients
      with gram-positive infections and to investigate the influence of type of
      infectious disease. METHODS: A two-compartment open model was adopted as a
      pharmacokinetic model. The nonlinear mixed-effects model was used to analyze the
      population pharmacokinetic models. RESULTS: We propose one general model and one
      infectious disease type-specific model. The general model showed that vancomycin
      clearance (CL) was linearly correlated with estimated creatinine clearance
      (CL(CR)) when CL(CR) was less than 85 mL/min, as expressed by CL(L/h) = 0.0322 x
      CL(CR) + 0.32. The distribution volumes of the central and peripheral compartment
      were different in healthy volunteers and patients with gram-positive infections.
      The infectious disease type-specific model showed that these differences were
      more pronounced in patients with pneumonia. CONCLUSION: The population
      pharmacokinetic parameters of vancomycin obtained here can be used to
      individualize the dosage of vancomycin in institutions with similar patient
      population characteristics.

PMID- 19583682
TI  - Multiple drug interactions - induced serotonin syndrome: a case report.
AB  - Serotonin syndrome is a potentially life-threatening disorder of excessive
      serotoninergic activity often due to drug interactions. We report a case of
      serotonin syndrome induced by pharmacokinetic and pharmacodynamic interactions
      between three different selective serotonin-reuptake inhibitors (SSRI) and
      possibly ciprofloxacin. Extreme caution is necessary in patients treated with
      serotonin-reuptake inhibitors who need to be switched to another antidepressant
      or when they require the addition of concomitant drugs, especially serotoninergic
      drugs and isoenzimes of cytochrome P450 inhibitors.

PMID- 19583683
TI  - Complete atrioventricular block associated with dapsone therapy: a rare
      complication of dapsone-induced hypersensitivity syndrome.
AB  - Dapsone is still widely used for a range of infectious and inflammatory diseases.
      A potential severe side-effect, known as dapsone-induced hypersensitivity
      syndrome (DHS), may occur. DHS is characterized by fever, skin rashes,
      lymphadenopathy and multiorgan dysfunction manifesting as hepatitis, cholangitis,
      pneumonitis, colitis, thyroiditis and myocarditis. However, DHS-associated
      complete atrioventricular block has not previously been reported. We describe
      here a 45-year-old Chinese woman who developed DHS after 5 weeks of dapsone
      therapy for pustular palmoplantar psoriasis. In addition to typical DHS symptoms,
      she experienced several episodes of syncope as a result of complete
      atrioventricular block which was successfully reversed with a permanent pacemaker
      implantation.

PMID- 19583684
TI  - Future perspectives in the treatment of atopic dermatitis.
AB  - Atopic dermatitis is a chronically relapsing inflammatory skin disease with an
      increasing prevalence. The guidelines for the treatment of atopic dermatitis
      enable us to manage many patients with atopic dermatitis under a global
      consensus, which also contributes to improving their quality of life. However,
      there remain some patients with atopic dermatitis whose symptoms cannot be
      satisfactorily controlled using the therapeutic management recommended by the
      guidelines. Recent genetic, immunological and physiological insights into the
      pathomechanisms of atopic dermatitis are expected to overcome the limitations of
      the currently available treatment. Advances in pharmacology and biotechnology
      will also provide more efficient and safer medications. In this review, the
      limitations of the currently available therapies and the advantages and
      disadvantages of new approaches for the treatment of atopic dermatitis including
      topical and systemic immunosuppressants as well as biologics and anti-pruritic
      agents are discussed. Potential new cellular targets for the treatment of atopic
      dermatitis are also illustrated.

PMID- 19583685
TI  - Epidemiology of pityriasis versicolor in Adana, Turkey.
AB  - Pityriasis versicolor is a common superficial mycoses of the skin. It is now
      recognized that the causative organisms of this infection are different species
      of Malassezia. The aim of this study was to determine the distribution of
      Malassezia species in patients with pityriasis versicolor in Adana, Turkey. In
      total, 97 patients positive for Malassezia elements, namely, yeast cells and
      short hyphae in microscopic examination, were included in the study. All samples
      were inoculated in plates containing modified Dixon's medium. However, only 44 of
      the patients (45.4%) showed Malassezia spp. in culture. Malassezia globosa
      (47.7%) was the most commonly isolated species followed by Malassezia furfur
      (36.4%) and Malassezia slooffiae (15.9%). Mixed Malassezia species were not
      isolated. In conclusion, M. globosa was found to be the predominant PV isolate in
      Adana, Turkey.

PMID- 19583686
TI  - Effects of oral antibiotic roxithromycin on quality of life in acne patients.
AB  - Macrolides are effective for inflammatory acne, but there are not many studies on
      roxithromycin. In this study, patients with acne were surveyed for improvement of
      their quality of life after treatment with roxithromycin. Patients were orally
      given roxithromycin 300 mg daily for 2-4 weeks. At the time of pre- and post
      treatment, the dermatologists graded the severity of acne symptoms, and the
      patients answered questionnaires. In 123 half faces of 76 patients, 80 half faces
      were improved, 42 half faces were not changed, and one half face was
      deteriorated. The score of "symptom and feeling" and "leisure" in DLQI-J and
      "emotions" and "symptoms" in Skindex-29-J were significantly decreased after
      roxithromycin treatment. Roxithromycin has a therapeutic effect on inflammatory
      acne and leads to improvement of quality of life in the patients.

PMID- 19583687
TI  - Clinicopathological features and T-cell receptor gene rearrangement findings of
      mycosis fungoides in patients younger than age 20 years.
AB  - Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma that
      usually arises in middle-aged or older people. The incidence of childhood MF is
      low, but studies in childhood MF suggests that the incidence is rising. The
      number of studies in childhood MF are few and there are currently no studies
      about childhood MF in Asians. We investigated the clinicopathological features, T
      cell receptor (TCR) gene rearrangement findings, treatment and follow up in
      childhood MF. The retrospective study was performed on a population consisting of
      23 MF patients aged 4-19 years. The duration of the disease ranged from 1 month
      to 10 years (mean, 2.7 years). In Tumor-Node-Metastasis classifications, all
      cases were confined to stage IA or IB. Histopathological findings revealed
      epidermotropism and perivascular infiltrates, epidermotropism in the
      infundibulum, Pautrier's microabscess, haloed lymphocytes, epidermal lymphocytes
      larger than dermal lymphocytes, atypical cells with hyperchromatic nuclei and
      wiry bundles of collagen. TCRgamma gene rearrangement was performed except for
      four patients, and monoclonality was detected in 16 of 19 cases (84%). Treatment
      was done with psoralen and ultraviolet (UV)A, UVA1, narrow-band UVB, topical
      steroid, retinoic acid and calcipotriol. Most patients showed a good response. At
      a mean follow up of 90.4 months, no patient had either an exacerbation of the
      disease or extracutaneous involvement. Compared with adult-onset MF, MF in
      children may show a variety of clinical features. It is considered to have a good
      prognosis. Moreover, histopathological study and TCR gene rearrangement study can
      help in the diagnosis of MF in children.

PMID- 19583688
TI  - Rat marrow-derived multipotent adult progenitor cells differentiate into skin
      epidermal cells in vivo.
AB  - Wound repair and functional reconstruction are two key aspects for treatment of
      skin injury. Research on cell source for skin repair has become a focus of study.
      The immune rejection induced by allograft cells and the limited source of
      autologous epidermal stem cells have led to more attention on the multipotent
      adult progenitor cells (MAPC). In this study, we examined the influence of the
      local environment of skin injury on the migration and differentiation of MAPC in
      nude mice. The homing of MAPC to the wounds and the epidermal differentiation of
      MAPC were investigated by detecting the expression of specific antigens of rat
      major histocompatibility complex I (MHC-I) antigen and the tracing markers. Three
      weeks after transplantation, hair follicle-like structure appeared and rat MHC-I
      antigen was positive in the follicles of the healed skin. PKH26-labeled cells
      expressing cytokeratin were found in the regenerated follicle-like structures,
      sebaceous glands and sweat glands. Our findings indicate that MAPC can migrate to
      the skin injury site and the hair follicles, and participate in skin wound
      healing by differentiating into epidermal cells, which contributes to the
      theoretical research of MAPC plasticity and provides theoretical evidence for
      clinical application of transplantation therapy with MAPC.

PMID- 19583690
TI  - Stewart-Bluefarb syndrome: a case report with angiographic findings.
AB  - Acroangiodermatitis is a group of benign, angioproliferative cutaneous disease
      caused by chronic venous insufficiency, acquired or congenital arteriovenous
      shunts and limb paralysis. Stewart-Bluefarb syndrome is the type of
      acroangiodermatitis which is associated with a congenital arteriovenous
      malformation. This is a rare syndrome characterized by cutaneous kaposiform
      lesions that usually onset at the second decade. In this report, a case of
      acroangiodermatitis associated with a congenital arteriovenous malformation,
      which has been diagnosed after 40 years, is described.

PMID- 19583689
TI  - Comparative study of nail sampling techniques in onychomycosis.
AB  - Onychomycosis is a common problem. Obtaining accurate laboratory test results
      before treatment is important in clinical practice. The purpose of this study was
      to compare results of curettage and drilling techniques of nail sampling in the
      diagnosis of onychomycosis, and to establish the best technique and location of
      sampling. We evaluated 60 patients suffering from distal and lateral subungual
      onychomycosis and lateral subungual onychomycosis using curettage and vertical
      and horizontal drilling sampling techniques from three different sites of the
      infected nail. KOH examination and fungal culture were used for detection and
      identification of fungal infection. At each sample site, the horizontal drilling
      technique has a better culture sensitivity than curettage. Trichophyton rubrum
      was by far the most common pathogen detected by both techniques from all sampling
      sites. The drilling technique was found to be statistically better than curettage
      at each site of sampling, furthermore vertical drilling from the proximal part of
      the affected nail was found to be the best procedure for nail sampling. With each
      technique we found that the culture sensitivity improved as the location of the
      sample was more proximal. More types of pathogens were detected in samples taken
      by both methods from proximal parts of the affected nails.

PMID- 19583691
TI  - Drug eruption due to intravesical instillations of both epirubicin and mitomycin
      C.
AB  - We present the first patient to develop drug eruption due to intravesical
      instillations of both epirubicin and mitomycin C. A 58-year-old-man underwent
      transurethral resection (TUR) for superficial bladder carcinoma followed by
      instillations of intravesical chemotherapy. Immediately after TUR, the first
      instillation of epirubicin was performed. Two days after the first instillation,
      the patient developed generalized erythema of the face, trunk, upper and lower
      limbs. Two days after the second instillation, the patient developed severe
      generalized erythema and was diagnosed as having drug eruption due to
      intravesical instillations of epirubicin by the dermatologist. Instead of
      epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the
      first instillation of mitomycin C, the patient again developed severe generalized
      erythema and was diagnosed as having drug eruption due to intravesical
      instillation of mitomycin C. Drug eruption after the first instillation of
      epirubicin might have been due to drug toxicity of the agent. However, drug
      eruptions after the second instillation of epirubicin and the first instillation
      of mitomycin C might have been due to allergic reactions to the drugs. The
      patient has not received any further intravesical chemotherapy and has not
      demonstrated any such a drug eruption again.

PMID- 19583692
TI  - Necrotizing fasciitis and myonecrosis "synergistic necrotizing cellulitis" caused
      by Bacillus cereus.
AB  - Our patient was a 37-year-old man with diabetes mellitus and hepatopathy as
      underlying diseases. Swelling, erythema and pain appeared in the left upper limb
      on the day before the initial examination. On examination, diffuse purpura was
      noted on the left upper limb, and, as it rapidly extended to the left upper
      trunk, emergency surgery was performed. Intraoperatively, gas-producing necrosis
      was observed not only in subcutaneous tissues but also from the fascia to muscle
      tissues, and the condition resembled clostridial gas gangrene. However, as the
      culturing of samples from the lesion yielded Bacillus cereus, a diagnosis of
      necrotizing fasciitis and myonecrosis (synergistic necrotizing cellulitis) due to
      B. cereus was made. While the patient developed a serious condition due to sepsis
      and disseminated intravascular coagulation, he could be saved by early
      debridement and intensive treatment with an appropriate selection of antibiotics.

PMID- 19583693
TI  - Papular acantholytic dyskeratosis of the vulva.
AB  - We describe a 63-year-old woman with an asymptomatic papular eruption on the
      vulva. Clinically, the lesions showed multiple pin-head-sized whitish papules on
      the labia major. Histologically, the biopsy specimen showed acantholysis
      throughout the epidermis with the presence of dyskeratotic cells resembling corps
      ronds and grains, hyperkeratosis and parakeratosis. These clinical and
      histological findings were consistent with the diagnosis of papular acantholytic
      dyskeratosis of the vulva which is a rare disorder, first described in 1984.

PMID- 19583694
TI  - Successful treatment of single lymph node metastasis of melanoma with carbon ion
      radiotherapy and chemotherapy.

PMID- 19583695
TI  - Feasibility of COL1A1-PDGFB fusion gene detection to evaluate surgical margins in
      dermatofibrosarcoma protuberans.

PMID- 19583696
TI  - Genetic divergence is more tightly related to call variation than landscape
      features in the Amazonian frogs Physalaemus petersi and P. freibergi.
AB  - Behavioural isolation from divergence in male advertisement calls and female
      preferences is hypothesized to cause genetic divergence and speciation in the
      Amazonian frogs Physalaemus petersi and P. freibergi, yet the importance of call
      variation and landscape features in genetic divergence is unresolved. We tested
      for correlations between genetic divergence at microsatellite loci and (1) call
      variables; and (2) landscape variables among 10 populations of these frogs.
      Genetic divergence was not correlated with geographical distance, rivers or
      elevation. There was a strong positive relationship, however, between genetic
      divergence and inter-population differences in one call variable, whine dominant
      frequency. Effective population sizes varied among sites (range = 15-846) and
      were often small, suggesting that genetic drift could influence call evolution.
      Evidence for fine-scale genetic structure within sites was also found. Our
      results support the hypothesis that behavioural isolation from divergence in male
      calls and female preferences causes genetic divergence and speciation.

PMID- 19583697
TI  - Indirect effects of FRIGIDA: floral trait (co)variances are altered by seasonally
      variable abiotic factors associated with flowering time.
AB  - Reproductive timing is a critical life-history event that could influence the
      (co)variation of traits developing later in ontogeny by regulating exposure to
      seasonally variable factors. In a field experiment with Arabidopsis thaliana, we
      explore whether allelic variation at a flowering-time gene of major effect
      (FRIGIDA) affects (co)variation of floral traits by regulating exposure to
      photoperiod, temperature, and moisture levels. We detect a positive latitudinal
      cline in floral organ size among plants with putatively functional FRI alleles.
      Statistically controlling for bolting day removes the cline, suggesting that
      seasonal abiotic variation affects floral morphology. Both photoperiod and
      precipitation at bolting correlate positively with the length of petals, stamens,
      and pistils. Additionally, floral (co)variances differ significantly across FRI
      backgrounds, such that the sign of some floral-trait correlations reverses.
      Subsequent experimental manipulations of photoperiod and water availability
      demonstrate direct effects of these abiotic factors on floral traits. In sum,
      these results highlight how the timing of life-history events can affect the
      expression of traits developing later in ontogeny, and provide some of the first
      empirical evidence for the effects of major genes on evolutionary potential.

PMID- 19583698
TI  - Ritual fights and male reproductive success in a human population.
AB  - Ritual fights are widespread across human populations. However, the evolutionary
      advantage associated with this behaviour is unclear because these fights rarely
      provide direct benefits such as territory, resources or mates. Here, the
      reproductive success of men competing in a traditional ritual fight, Sereer
      wrestling, was investigated for the first time. Involvement in wrestling had a
      significant positive effect on men's number of offspring and a marginally
      significant effect on polygyny, controlling for age, body condition and socio
      economic status. These positive effects suggest that being involved in wrestling
      competition provides prestige, facilitating access to mates and thereby
      increasing fecundity. However, when women were interviewed on their preference
      concerning qualities of potential mates, the quality 'being involved in wrestling
      competition' was poorly ranked. This discrepancy may arise either from deceptive
      reports or from discordance between parents and daughters in the choice of a
      husband.

PMID- 19583699
TI  - How is sexual conflict over parental care resolved? A meta-analysis.
AB  - Biparental care of offspring is both a form of cooperation and a source of
      conflict. Parents face a trade-off between current and future reproduction:
      caring less for the current brood allows individuals to maintain energy reserves
      and increase their chances of remating. How can selection maintain biparental
      care, given this temptation to defect? The answer lies in how parents respond to
      changes in each other's effort. Game-theoretical models predict that biparental
      care is evolutionarily stable when reduced care by one parent leads its partner
      to increase care, but not so much that it completely compensates for the lost
      input. Experiments designed to reveal responses to reduced partner effort have
      mainly focused on birds. We present a meta-analysis of 54 such studies, and
      conclude that the mean response was indeed partial compensation. Males and
      females responded differently and this was in part mediated by the type of
      manipulation used.

PMID- 19583700
TI  - Cell-mediated immunity and multi-locus heterozygosity in bluethroat nestlings.
AB  - Recent evidence suggests that marker-based heterozygosity-fitness correlations
      may be driven by only one or a few markers, indicating local heterozygosity
      effects caused by linkage disequilibrium with functional genes. In this study, we
      investigated the relationship between microsatellite heterozygosity and a measure
      of cell-mediated immunity (phytohaemagglutinin; PHA) in bluethroat (Luscinia s.
      svecica) nestlings using a full-sibling design. We found significant positive
      associations between PHA response and two different indices of microsatellite
      heterozygosity, i.e. multi-locus heterozygosity and mean d(2). However, model
      comparisons disclosed that both associations were more likely caused by local
      effects rather than general effects and that the two local effects appeared to be
      realized through two different genetic mechanisms. Our results indicate that both
      the random assortment of parental chromosomes during meiosis as well as
      inbreeding can drive heterozygosity-fitness correlations.

PMID- 19583701
TI  - Uncontrolled hemorrhage in insulin-dependent diabetic rats.
AB  - OBJECTIVES: Diabetes mellitus (DM) is a known risk factor for higher morbidity
      and mortality after trauma. The authors tested the hypothesis that there is a
      difference in the response to uncontrolled hemorrhage between normal euglycemic
      rats and insulin-dependent diabetic rats. METHODS: Thirty-one adult male Sprague
      Dawley rats were used in this study. Fifteen streptozocin (STZ)-injected rats
      became diabetic (DM+) 2 weeks after treatment. Sixteen rats served as nondiabetic
      controls (DM-). All rats were anesthetized with Althesin and their femoral
      arteries were catheterized via cutdown, allowing continuous monitoring of vital
      signs. Sixteen (eight DM-, eight DM+) rats underwent uncontrolled hemorrhage by
      75% tail amputation. Fifteen (eight DM-, seven DM+) rats served as non-hemorrhage
      controls. The mean arterial pressure (MAP), lactate, and cumulative hemorrhage
      volume per 100 g were measured pre-hemorrhage and then every 15 minutes post
      hemorrhage for 2 hours. Data were reported as mean +/- standard deviation.
      Interval data were analyzed by analysis of variance (two tails, alpha = 0.05).
      RESULTS: Pre-hemorrhage glucose was significantly higher (p < 0.001) in the DM+
      (357.9 +/- 22.2 mg/dL) versus DM- (125.7 +/- 9.7 mg/dL) rats. At baseline, there
      was no significant difference in weight, MAP, or lactate between DM+ and DM-
      rats. Body-weight-adjusted mean cumulative hemorrhage volume was significantly
      greater (p < 0.04) in diabetic rats (2.52 +/- 0.15 cm(3)/100 g body weight) than
      the nondiabetic rats (1.86 +/- 0.25 cm(3)/100 g body weight). CONCLUSIONS:
      Compared to nondiabetic rats, diabetic rats suffered a greater blood loss after
      the same uncontrolled vascular injury.

PMID- 19583702
TI  - Functions of glutamate transporters in cerebellar Purkinje cell synapses.
AB  - Glutamate transporters play a critical role in the maintenance of low
      extracellular concentrations of glutamate, which prevents the overactivation of
      post-synaptic glutamate receptors. Four distinct glutamate transporters,
      GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3 and EAAT4, are distributed in the molecular
      layer of the cerebellum, especially near glutamatergic synapses in Purkinje cells
      (PCs). This review summarizes the current knowledge about the differential roles
      of these transporters at excitatory synapses of PCs. Data come predominantly from
      electrophysiological experiments in mutant mice that are deficient in each of
      these transporter genes. GLAST expressed in Bergmann glia contributes to the
      clearing of the majority of glutamate that floods out of the synaptic cleft
      immediately after transmitter release from the climbing fibre (CF) and parallel
      fibre (PF) terminals. It is indispensable to maintain a one-to-one relationship
      in synaptic transmission at the CF synapses by preventing transcellular glutamate
      spillover. GLT-1 plays a similar but minor role in the uptake of glutamate as
      GLAST. Although the loss of neither GLAST nor GLT-1 affects cerebellar
      morphology, the deletion of both GLAST and GLT-1 genes causes the death of the
      mutant animal and hinders the folium formation of the cerebellum. EAAT4 removes
      the low concentrations of glutamate that escape from uptake by glial
      transporters, preventing the transmitter from spilling over into neighbouring
      synapses. It also regulates the activation of metabotropic glutamate receptor 1
      (mGluR1) in perisynaptic regions at PF synapses, which in turn affects mGluR1
      mediated events including slow EPSCs and long-term depression. No change in
      synaptic function is detected in mice that are deficient in EAAC1.

PMID- 19583703
TI  - Cardioprotection of bradykinin at reperfusion involves transactivation of the
      epidermal growth factor receptor via matrix metalloproteinase-8.
AB  - AIM: The endogenous autacoid bradykinin (BK) reportedly reduces myocardial
      infarct size when given exogenously at reperfusion. Muscarinic and opioid G
      protein-coupled receptors are equally protective and have been shown to couple
      through a matrix metalloproteinase (MMP)-dependent transactivation of the
      epidermal growth factor receptor (EGFR). Here we test whether BK protects the rat
      heart through the EGFR by an MMP-dependent pathway. METHODS: Infarct size was
      measured in isolated perfused rat hearts undergoing 30 min regional ischaemia
      followed by 120 min reperfusion. In additional studies HL-1 cardiomyocytes were
      loaded with tetramethylrhodamine ethyl to measure their mitochondrial membrane
      potential (Psim). Adding the calcium ionophore calcimycin, causes Psim-collapse
      presumably due to calcium-induced mitochondrial permeability transition. RESULTS:
      As expected, BK (100 nmol L(-1)) started 5 min prior to reperfusion reduced
      infarct size from 38.9 +/- 2.0% of the ischaemic zone in control hearts to 22.2
      +/- 3.3% (P < 0.001). Co-infusing the EGFR inhibitor AG1478, the broad-spectrum
      MMP-inhibitor GM6001, or a highly selective MMP-8 inhibitor abolished BK's
      protection, thus suggesting an MMP-8-dependent EGFR transactivation in the
      signalling. Eighty minutes of exposure to calcimycin reduced the mean cell
      fluorescence to 37.4 +/- 1.8% of untreated cells while BK could partly preserve
      the fluorescence and, hence, protect the cells (50.5 +/- 2.3%, P < 0.001). The BK
      induced mitochondrial protection could again be blocked by AG1478, GM6001 and MMP
      8 inhibitor. Finally, Western blotting revealed that BK's protection was
      correlated with increased phosphorylation of EGFR and its downstream target Akt.
      CONCLUSION: These results indicate that BK at reperfusion triggers its protective
      signalling pathway through MMP-8-dependent transactivation of the EGFR.

PMID- 19583704
TI  - Rapid and easy semi-quantitative evaluation method for diacylglycerol and
      inositol-1,4,5-trisphosphate generation in orexin receptor signalling.
AB  - AIM: Fluorescent protein-based indicators have enabled measurement of
      intracellular signals previously nearly inaccessible for studies. However,
      indicators showing intracellular translocation upon response suffer from serious
      limitations, especially the very time-consuming data collection. We therefore set
      out in this study to evaluate whether fixing and counting cells showing
      translocation could mend this issue. METHODS: Altogether three different
      genetically encoded indicators for diacylglycerol and inositol-1,4,5
      trisphosphate were transiently expressed in Chinese hamster ovary cells stably
      expressing human OX(1) orexin receptors. Upon stimulation with orexin-A, the
      cells were fixed with six different protocols. RESULTS: Different protocols
      showed clear differences in their ability to preserve the indicator's
      localization (i.e. translocation after stimulus) and its fluorescence, and the
      best results for each indicator were obtained with a different protocol. The
      concentration-response data obtained with cell counting are mostly comparable to
      the real-time translocation and biochemical data. CONCLUSION: The counting
      method, as used here, works at single time point and looses the single-cell
      quantitative aspect. However, it also has some useful properties. First, it
      easily allows processing of a 100- to 1000-fold higher cell numbers than real
      time imaging producing statistically consistent population-quantitative data much
      faster. Secondly, it does not require expensive real-time imaging equipment.
      Fluorescence in fixed cells can also be quantitated, though this analysis would
      be more time-consuming than cell counting. Thirdly, in addition to the
      quantitative data collection, the method could be applied for identifying
      responsive cells. This might be very useful in identification of e.g. orexin
      responding neurones in a large population of non-responsive cells in primary
      cultures.

PMID- 19583705
TI  - Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats
      is associated with increased acetylcholine-induced airway contractility.
AB  - AIM: We have recently reported that hypoxia stimulates transcription of the TrkB
      neurotrophin receptor in cultured cells via stabilization of hypoxia-inducible
      factor-1alpha. Here we investigated whether the expression of TrkB and other
      neurotrophin receptors is oxygen-sensitive also in vivo, and explored the
      functional consequences of an oxygen-regulated TrkB expression. METHODS: Rats
      were exposed either to 21% O(2) or 8% O(2) for 6 h and TrkB was analysed by
      reverse transcription real-time PCR, in situ mRNA hybridization, and
      immunological techniques. The importance of the brain-derived neurotrophic factor
      (BDNF)-TrkB pathway in the control of mechanical airway function was assessed on
      isolated tracheal segments from normoxic and hypoxic rats. RESULTS: TrkB
      transcripts were increased approx. 15-fold in the lungs of hypoxic rats, and the
      respiratory epithelium was identified as the site of enhanced TrkB expression in
      hypoxia. The TrkB ligand, BDNF, significantly increased the contractile response
      to acetylcholine (ACh) of isolated tracheal segments from hypoxic but not from
      normoxic rats. This effect of BDNF was prevented by pre-incubation of the tissue
      specimens with the tyrosine kinase inhibitor K252a and by mechanical removal of
      the TrkB containing airway epithelium. Likewise, the nitric oxide (NO) synthase
      inhibitor l-NAME abrogated the influence of BDNF on ACh-induced contractions of
      isolated tracheal segments from hypoxic rats. CONCLUSION: These results
      demonstrate that systemic hypoxia stimulates expression of the TrkB neurotrophin
      receptor in the airway epithelium. Furthermore, activation of TrkB signalling by
      BDNF in hypoxia enhances mechanical airway contractility to ACh through a
      mechanism that requires NO.

PMID- 19583706
TI  - Quality of performance of everyday activities in children with spina bifida: a
      population-based study.
AB  - AIM: The aim of this study was to evaluate the quality of the performance of
      everyday activities in children with spina bifida. METHODS: Fifty children with
      spina bifida (of 65 children in a geographic cohort), aged 6 to 14 years, were
      evaluated with Assessment of Motor and Process Skills. RESULTS: Compared with age
      normative values, 60% of the children with spina bifida were found to have motor
      ability measures below 2 SD and 48% process ability measures below 2 SD. Most of
      the children with spina bifida had difficulties performing well-known everyday
      activities in an effortless, efficient and independent way, relating to both
      motor and process skills. The motor skills hardest to accomplish involved motor
      planning and the process skills hardest to accomplish were adaptation of
      performance and initiations of new steps, thus actually getting the task done.
      CONCLUSION: To reach autonomy in life, children with spina bifida may need
      particular guidance to learn not only how to do things but also how to get things
      done.

PMID- 19583707
TI  - Reversibility of acute intermediate phase bilirubin encephalopathy.
AB  - AIM: To show the potential for reversing acute intermediate to advanced phase
      bilirubin encephalopathy. METHODS: Case studies. RESULTS: Six extremely jaundiced
      infants had symptoms of intermediate to advanced phase acute bilirubin
      encephalopathy. The infants were treated aggressively. Two patients had brain
      magnetic resonance imaging showing increased signals in the globus pallidus. On
      follow-up, all infants are neurologically normal. CONCLUSIONS: Intermediate-to
      advanced stage acute bilirubin encephalopathy may occasionally be reversible.
      These cases provide a strong argument in favour of rapid and aggressive
      intervention in infants presenting with extreme jaundice and neurological
      symptoms.

PMID- 19583708
TI  - Thiopental pharmacokinetics in newborn infants: a case report of overdose.
AB  - Thiopental may be used for sedation before intubation in newborn infants. A boy,
      born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed
      thiopental 3 mg/kg before intubation. He developed temporary hypotension and
      oxygen desaturation, and remained unconscious for longer than expected with a
      suppressed electroencephalography for 48 h. Serum thiopental concentration was
      82, 59, 42 and 32 micromol/L after 20 min and 6, 24 and 68 h respectively. Serum
      concentrations from five newborn infants at the same time points after intubation
      with the same thiopental dose were used as reference values, and indicated a 10
      fold overdose in the index case. The cause of the overdose could not be
      identified. The infant recovered; cerebral magnetic resonance imaging at the age
      of 42 gw and psychomotor development at 2 years were normal. These results show
      that thiopental concentrations are variable in neonates and there is a high risk
      of dosage error as no specific paediatric formulation is available. CONCLUSION:
      Well-designed procedures and continuous education are required to prevent errors
      and adverse events during drug delivery to newborn infants. To develop a safe
      method of administration for thiopental, an extended pharmacokinetic and
      pharmacodynamic study in neonates is warranted.

PMID- 19583709
TI  - Long-term outcome of non-fistulizing (ulcers, stricture) perianal Crohn's disease
      in patients treated with infliximab.
AB  - BACKGROUND: In Crohn's disease, anal ulcers and stricture can be disabling. AIM:
      To evaluate long-term outcome of non-fistulizing perianal Crohn's disease under
      infliximab. METHODS: The medical records of 99 patients with non-fistulizing
      perianal Crohn's disease at first infliximab infusion were reviewed. Complete
      responses (ulcer healing or stricture regression) after induction infliximab
      therapy and at the maximal follow-up were assessed. RESULTS: Ninety-four patients
      (94.9%) had ulcers, 22 (22.2%) had stricture and 31 (31.3%) had draining perianal
      fistulas at first infliximab infusion. After infliximab induction therapy, 40/94
      (42.5%) patients with ulcers, 4/22 (18.2%) with stricture and 10/31 (32.2%) with
      fistulas had a complete response. Eight patients were lost to follow-up. After a
      median follow-up of 175 weeks (range, 13-459), complete response rates for
      ulcers, stricture and fistulas were 72.3% (68/94), 54.5% (12/22) and 54.8%
      (20/31) respectively. Long-term response for cavitating ulcer was positively
      associated with concomitant immunosuppressant use (P = 0.017) and older age (P =
      0.049). Among the 12 patients with complete regression of stricture, 6 patients
      also had anal dilatation. Complete response was associated with perianal pain
      relief and disappearance of soiling. Three patients with ulcers developed an anal
      abscess. CONCLUSIONS: Infliximab therapy may be effective in inducing and
      maintaining response for ulcers.

PMID- 19583710
TI  - Antinociceptive activity of a new benzofuranone derived from a chalcone.
AB  - Chalcones represent an important group of natural or synthetic compounds with a
      variety of biological activities including antinociceptive and anti-inflammatory
      ones. The aim of this work was the synthesis of a new benzofuranone compound and
      evaluation of its antinociceptive potential in mice. The new benzofuranone 4 was
      synthesized from chalcone 3. The antinociceptive activity of 4 was determined by
      writhing, formalin, capsaicin, and glutamate and hot-plate tests. Compound 4
      caused potent and dose-related inhibition against the writhing test with ID50 6.1
      (5.1-7.6) MUmol/kg, i.p., being about 15 times more active than the reference
      drugs, acetyl salicylic acid and acetaminophen. It was also effective in a dose
      dependent manner in significantly reducing the painful stimulus in both phases of
      formalin, in the capsaicin and in the glutamate test with ID50 values of 27.3
      (24.5-30.6) and 18.9 (18.5-19.4) MUmol/kg (first and second phase), 12.6 (9.8
      16.2) and 24.5 (20.4-29.6) MUmol/kg respectively. The results showed that the
      studied compound exhibits both central and peripheral antinociceptive activities
      and might be further used as a model to obtain new and more potent analgesic
      drugs.

PMID- 19583711
TI  - Rosuvastatin attenuates heart failure and cardiac remodelling in the ageing
      spontaneously hypertensive rat.
AB  - 3-hydroxy-3-methylglutaryl(HMG)-Coenzyme(Co)A reductase inhibitors such as
      rosuvastatin may improve clinical status in patients with hypertension and heart
      failure. The ageing spontaneously hypertensive rat (SHR) closely mimics the
      chronic heart failure disease process observed in humans. This study examined the
      structural and functional changes in the cardiovascular system of 15-month-old
      SHR and normotensive Wistar-Kyoto (WKY) rats treated with rosuvastatin (20
      mg/kg/day perorally) for 24 weeks. Cardiovascular structure and function were
      monitored serially by echocardiography. At 21 months, ex vivo Langendorff,
      electrophysiological or histological studies were performed. Chronic rosuvastatin
      treatment attenuated elevations of left ventricular wet weight (mg/g body weight:
      21-month WKY, 2.30 +/- 0.04; 15-month SHR, 3.03 +/- 0.08; 21-month SHR, 4.09 +/-
      0.10; 21-month SHR + rosuvastatin, 3.50 +/- 0.13), myocardial extracellular
      matrix content (% left ventricular area: 21-month WKY, 7.6 +/- 0.5; 15-month SHR,
      13.2 +/- 0.8; 21-month SHR 19.6 +/- 1.0; 21-month SHR with rosuvastatin 14.6 +/-
      1.2) and diastolic stiffness (kappa: 21-month WKY, 24.9 +/- 0.6; 15-month SHR,
      26.4 +/- 0.4; 21-month SHR, 33.1 +/- 0.8; 21-month SHR + rosuvastatin, 27.5 +/-
      0.6) as well as attenuating the deterioration of systolic and diastolic function
      (fractional shortening %: 21-month WKY, 66 +/- 2; 15-month SHR, 51 +/- 3; 21
      month SHR, 38 +/- 3; 21-month SHR + rosuvastatin, 52 +/- 4). There was no effect
      on the increased systolic blood pressure, plasma low-density lipoprotein
      concentrations or the prolonged action potential duration. Thus, chronic
      rosuvastatin treatment may attenuate myocardial dysfunction in heart failure by
      preventing fibrosis.

PMID- 19583713
TI  - Monthly itraconazole versus classic homeopathy for the treatment of recurrent
      vulvovaginal candidiasis: a randomised trial.
AB  - OBJECTIVE: Antimycotics effectively treat sporadic and recurrent vulvovaginal
      candidiasis (RVVC). Classic homeopathy (CH) is also used to treat this condition.
      We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC
      episodes. DESIGN: Single-centre, prospective, randomised trial. SAMPLE: One
      hundred-and-fifty patients with a history of RVVC and an acute episode of VVC.
      METHODS: Women were randomised into 3 groups: itraconazole with lactobacilli
      (group 1), itraconazole without lactobacilli (group 2) and CH (group 3).
      Itraconazole treatment of acute infection was followed by a 6-month maintenance
      regimen with monthly single-day itraconazole (200 mg bid). Women in group 1 were
      given additional vaginal lactobacilli for 6 days per month throughout the
      maintenance regimen Thereafter, patients were followed without treatment for 6
      months. CH treatment was performed for 12 months. RESULTS: Women in groups 1 and
      2 reached a culture-free status significantly earlier than women in group 3 (log
      rank test; P < 0.0001). Specifically, before the start of the maintenance
      regimen, 44 of 49 women (89.8%) in group 1 and 40 of 47 women (85%) in group 2
      were free of Candida detectable by culture, 22 of 46 (47%) women in group 3
      reached a culture-free status after the first visit, but had a recurrence
      significantly earlier compared with women in groups 1 and 2 (log-rank test; P =
      0.002). After 12 months, 19 of 25 (76%) women in group 1, 18 of 23 (78%) women in
      group 2 and 9 of 23 (39%) women in group 3 were free of culture-detectable
      Candida. Assessment of RVVC-associated complaints by VAS score showed that women
      in group 3 had a significantly higher level of discomfort (36.8, 25.1 and 27.7
      respectively; P < 0.001) and were significantly less satisfied (59.2, 68.2 and
      71.7 respectively; P < 0.001) than patients in groups 1 and 2. CONCLUSIONS:
      Monthly cycle-dependent itraconazole is more effective than CH in the treatment
      of RVVC. Lactobacilli do not confer an added benefit.

PMID- 19583712
TI  - After-effects reported by women following colposcopy, cervical biopsies and
      LLETZ: results from the TOMBOLA trial.
AB  - OBJECTIVE: Few studies have investigated physical after-effects of colposcopy. We
      compared post-colposcopy self-reported pain, bleeding, discharge and menstrual
      changes in women who underwent: colposcopic examination only; cervical punch
      biopsies; and large loop excision of the transformation zone (LLETZ). DESIGN:
      Observational study nested within a randomised controlled trial. SETTING:
      Grampian, Tayside and Nottingham. POPULATION: Nine hundred-and-twenty-nine women,
      aged 20-59, with low-grade cytology, who had completed their initial colposcopic
      management. METHODS: Women completed questionnaires on after-effects at
      approximately 6-weeks, and on menstruation at 4-months, post-colposcopy. MAIN
      OUTCOME MEASURES: Frequency of pain, bleeding, discharge; changes to first
      menstrual period post-colposcopy. RESULTS: Seven hundred-and-fifty-one women
      (80%) completed the 6-week questionnaire. Of women who had only a colposcopic
      examination, 14-18% reported pain, bleeding or discharge. Around half of women
      who had biopsies only and two-thirds treated by LLETZ reported pain or discharge
      (biopsies: 53% pain, 46% discharge; LLETZ: 67% pain, 63% discharge). The
      frequency of bleeding was similar in the biopsy (79%) and LLETZ groups (87%).
      Women treated by LLETZ reported bleeding and discharge of significantly longer
      duration than other women. The duration of pain was similar across management
      groups. Forty-three percent of women managed by biopsies and 71% managed by LLETZ
      reported some change to their first period post-colposcopy, as did 29% who only
      had a colposcopic examination. CONCLUSIONS: Cervical punch biopsies and,
      especially, LLETZ carry a substantial risk of after-effects. After-effects are
      also reported by women managed solely by colposcopic examination. Ensuring that
      women are fully informed about after-effects may help to alleviate anxiety and
      provide reassurance, thereby minimising the harms of screening.

PMID- 19583714
TI  - Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised
      controlled trial.
AB  - OBJECTIVE: To compare vaginal repair augmented by mesh with traditional
      colporrhaphy for the treatment of pelvic organ prolapse. DESIGN: Prospective
      randomised controlled trial. SETTING: Tertiary teaching hospital. POPULATION: One
      hundred and thirty-nine women with stage >or=2 prolapse according to the pelvic
      organ prolapse quantification (POP-Q) system requiring both anterior and
      posterior compartment repair. METHODS: Subjects were randomised to anterior and
      posterior vaginal repair with mesh augmentation (mesh group, n = 69) or
      traditional anterior and posterior colporrhaphy (no mesh group, n = 70). MAIN
      OUTCOME MEASURES: The primary outcome was the absence of POP-Q stage >or=2
      prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes
      and satisfaction with surgery. Complications were also reported. RESULTS: For
      subjects attending the 12-month review, success in the mesh group was 81.0% (51
      of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not
      significantly different (P-value = 0.07). A high level of satisfaction with
      surgery and improvements in symptoms and quality-of-life data were observed at 12
      months compared to baseline in both groups, but there was no significant
      difference in these outcomes between the two groups. Vaginal mesh exposure
      occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported
      by five of 30 (16.7%) sexually active women in the mesh group and five of 33
      (15.2%) in the no mesh group at 12 months. CONCLUSION: In this study, vaginal
      surgery augmented by mesh did not result in significantly less recurrent prolapse
      than traditional colporrhaphy 12 months following surgery.

PMID- 19583716
TI  - The need for ureteric re-implantation during augmentation cystoplasty: video
      urodynamic evaluation.
AB  - OBJECTIVE: To evaluate video-urodynamic (VUD) results before and after surgery in
      children with high-pressure, low-compliance bladders and vesico-ureteric reflux
      (VUR), who had augmentation cystoplasty with no antireflux surgery, hypothesising
      that in these patients, poor preoperative bladder dynamics is not always the
      cause of the associated VUR, as VUR persists in some patients. PATIENTS AND
      METHODS: We assessed objective VUD criteria where antireflux surgery might
      potentially be necessary to avoid reflux after augmentation, and retrospectively
      evaluated the clinical consequences of persistent VUR and compared it to those
      whom VUR resolved. In all, 19 patients with VUR and hypocompliant bladders (mean
      age 11.4 years, range 5-21) had augmentation ileocystoplasty. Lower urinary tract
      function was assessed before surgery and at 3 and 6 months afterward with VUD.
      Symptomatic febrile urinary tract infections (UTIs) and progressive renal
      scarring on scintigraphy were retrospectively evaluated in all patients. RESULTS:
      VUR persisted in nine patients despite a low-pressure bladder. In all patients
      with persistent VUR, VUD at 6 months after surgery showed that VUR started at low
      bladder volumes (mean 29.6 mL, range 19-52) and low pressures (mean 14.6 cmH(2)O,
      range 9.6-25) when compared to the group with no persistent VUR. Before surgery
      VUD showed that reflux started at the beginning of the filling phase (mean 14.8
      mL, range 8-33) with very low intravesical pressures (mean 7.8 cmH(2)O, range 4
      17) in these nine patients. During the follow-up febrile UTIs were significantly
      more frequent in the group with persistent VUR. One patient had progressive renal
      scarring on scintigraphy after cystoplasty. CONCLUSION: Preoperative VUD findings
      might be a very important predictor of the spontaneous resolution of VUR. In
      these patients concomitant VUR should be corrected simultaneously during bladder
      augmentation if it starts at low pressures on preoperative VUD, as persistence of
      VUR can induce scarring from febrile UTIs.

PMID- 19583717
TI  - Current salvage methods for recurrent prostate cancer after failure of primary
      radiotherapy.
AB  - We reviewed the current salvage methods for patients with local recurrent
      prostate cancer after primary radiotherapy (RT), using a search of relevant
      Medline/PubMed articles published from 1982 to 2008, with the following search
      terms: 'radiorecurrent prostate cancer, local salvage treatment, salvage radical
      prostatectomy (RP), salvage cryoablation, salvage brachytherapy, salvage high
      intensity focused ultrasound (HIFU)', and permutations of the above. Only
      articles written in English were included. The objectives of this review were to
      analyse the eligibility criteria for careful selection of appropriate patients
      and to evaluate the oncological results and complications for each method. There
      are four whole-gland re-treatment options (salvage RP, salvage cryoablation,
      salvage brachytherapy, salvage HIFU) for RT failure, although others might be in
      development or investigations. Salvage RP has the longest follow-up with
      acceptable oncological results, but it is a challenging technique with a high
      complication rate. Salvage cryoablation is a feasible option, especially using
      third-generation technology, whereby the average biochemical disease-free
      survival rate is 50-70% and there are fewer occurrences of severe complications
      such as recto-urethral fistula. Salvage brachytherapy, with short-term cancer
      control, is comparable to other salvage methods but depends on cumulative dosage
      limitation to target tissues. HIFU is a relatively recent option in the salvage
      setting. Both salvage brachytherapy and HIFU require more detailed studies with
      intermediate and long-term follow-up. As these are not prospective, randomized
      studies and the definitions of biochemical failure varied, there are limited
      comparisons among these different salvage methods, including efficacy. In the
      focal therapy salvage setting, the increased use of thermoablative methods for
      eligible patients might contribute to reducing complications and maintaining
      quality of life. The problem to effectively salvage patients with locally
      recurrent disease after RT is the lack of diagnostic examinations with sufficient
      sensitivity and specificity to detect local recurrence at an early curable stage.
      Therefore, a more strict definition of biochemical failure, improved imaging
      techniques, and accurate specimen mapping are needed as diagnostic tools.
      Furthermore, universal selection criteria and an integrated definition of
      biochemical failure for all salvage methods are required to determine which
      provides the best oncological efficacy and least comorbidity.

PMID- 19583718
TI  - Blue-sky thinking about blue-light cystoscopy.

PMID- 19583715
TI  - Obstetric interventions for babies born before 28 weeks of gestation in Europe:
      results of the MOSAIC study.
AB  - OBJECTIVE: To describe obstetric intervention for extremely preterm births in ten
      European regions and assess its impact on mortality and short term morbidity.
      DESIGN: Prospective observational cohort study. SETTING: Ten regions from nine
      countries participating in the 'Models of Organising Access to Intensive Care for
      Very Preterm Babies in Europe' (MOSAIC) project. POPULATION: All births from 22
      to 29 weeks of gestation (n = 4146) in 2003, excluding terminations of pregnancy.
      METHODS: Comparison of three obstetric interventions (antenatal corticosteroids,
      antenatal transfer and caesarean section for fetal indication) rates at 22-23, 24
      25 and 26-27 weeks to that at 28-29 weeks and the association of the level of
      intervention with pregnancy outcome. MAIN OUTCOME MEASURES: Use of antenatal
      corticosteroids, antenatal transfer and caesarean section by two-week gestational
      age groups as well as a composite score of these three interventions. Outcomes
      included stillbirth, in-hospital mortality and intraventricular haemorrhage (IVH)
      grades III and IV and/or periventricular leucomalacia (PVL) and bronchopulmonary
      dysplasia (BPD). RESULTS: There were large differences between regions in
      interventions for births at 22-23 and 24-25 weeks. Differences were most
      pronounced at 24-25 weeks; in some regions these babies received the same care as
      babies of 28-29 weeks, whereas elsewhere levels of intervention were distinctly
      lower. Before 26 weeks and especially at 24-25 weeks, there was an association
      between the composite intervention score and mortality. No association was
      observed at 26-27 weeks. For survivors at 24-25 weeks, the intervention score was
      associated with higher rates of BPD, but not with IVH or PVL. CONCLUSIONS: There
      are large differences between European regions in obstetric practices at the
      lower limit of viability and these are related to outcome, especially at 24-25
      weeks.

PMID- 19583719
TI  - Para-anastomotic haematoma volume predicts the presence of anastomotic
      extravasation after radical retropubic prostatectomy.
AB  - OBJECTIVE: To determine the mechanism for delayed healing of the urinary
      anastomosis after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS:
      The volumes of the para-anastomotic haematoma (PHV) and anastomotic extravasation
      were measured by ultrasonography in 95 men after RRP. The performance
      characteristics of PHV for predicting urinary extravasation were ascertained and
      compared with that of postoperative blood loss, measured as the difference
      between the haematocrit immediately after RRP and that at discharge. RESULTS: The
      sensitivity and specificity of PHV for predicting urinary extravasation at a
      threshold of 37 mL was 100% and 96%, respectively. PHV was superior to
      postoperative blood loss in predicting anastomotic extravasation, as shown by an
      area under the receiver operating curve of 0.99 vs 0.91, respectively.
      CONCLUSIONS: Our findings provide compelling evidence that delayed healing of the
      anastomosis after RRP is due to distraction forces secondary to a pelvic
      haematoma. The accuracy of PHV as a predictor of anastomotic extravasation
      suggests that this measurement might replace cystography for assessing
      anastomotic integrity after RRP.

PMID- 19583721
TI  - Only connect.

PMID- 19583720
TI  - Bladder neck contracture after retropubic radical prostatectomy: incidence and
      risk factors from a large single-surgeon experience.
AB  - OBJECTIVE: To examine a large, single-surgeon series of patients with prostate
      cancer who underwent retropubic radical prostatectomy (RRP) for men with
      postoperative bladder neck contractures (BNCs). PATIENTS AND METHODS: From 1983
      to 2007, 4132 men underwent RRP for prostate cancer by one surgeon. All patients
      had BN reconstruction with mucosal eversion. The bladder to membranous urethral
      anastomosis was made using six 2/0 chromic catgut sutures over an 18 F Foley
      catheter. The catheter was left in place for 10 days. Data from these men is
      stored in a prospective database, which was reviewed in this study for men with
      BNCs after RRP. Men with BNCs were compared with all other men in the series to
      determine risk factors for BNC development. RESULTS: Overall, BNCs developed in
      110 patients (2.5%). Examining our last 500 patients there was a contemporary BNC
      rate of <1%. The median (range) follow-up was 44 (12-233) months. Tumour
      characteristics were similar in the men with BNCs and those with no BNCs, and the
      rates of organ-confined disease were also similar (65% vs 70%, P = 0.27). Men
      with BNCs had higher median preoperative prostate-specific antigen (PSA) levels
      (6.7 vs 5.7 mg/dL; P = 0.009) and were more likely to have PSA failure after RRP
      (30% vs 16%, P < 0.001). On multivariate analysis, non-nerve sparing (P = 0.003)
      and a surgical date before 1992 (P < 0.001) were significant predictors of BNC.
      Patients with BNCs had lower potency rates (49% vs 63%, P < 0.003) and continence
      rates (88% vs 94%, P = 0.07) at the 18-month follow-up. CONCLUSIONS: BNCs are
      rare, occurring in <1% in our modern series. The important surgical factors in
      preventing BNCs are to avoid closing the BN too tightly and attaining good
      apposition of the BN with the urethral stump with a watertight closure. BNCs are
      more common with non-nerve-sparing surgery and early in a surgeon's experience.

PMID- 19583722
TI  - Cardiovascular risk and the urological patient.

PMID- 19583723
TI  - The fate of an unsatisfactory urine cytology test among patients with urothelial
      carcinoma.
AB  - OBJECTIVE: To determine the outcome of patients with a urinary cytology test that
      is unsatisfactory (UUCyt) for evaluation (<50 urothelial cells) to guide the
      clinical decision-making process, as currently there are no guidelines to aid in
      interpreting this result and directing further investigations. PATIENTS AND
      METHODS: We retrospectively reviewed 142 patients, with 265 instances of UUCyt,
      in our bladder cancer database and by chart review. The cytology, cystoscopy and
      pathology results in the subsequent 12 months after a UUCyt result were reviewed,
      and the incidence of new and recurrent genitourinary tract cancers was
      calculated. RESULTS: All patients had a previous history of, or developed,
      urothelial carcinoma during the follow-up. There were 41 instances (16.3%) in
      which bladder cancer was evident at the time of the UUCyt and 29% of these
      tumours were high-grade. There were another 44 instances (17.5%) in which new or
      recurrent bladder cancer developed in the subsequent year after a UUCyt test, and
      many (38.6%) of these tumours were high-grade. CONCLUSION: The incidence of
      urothelial carcinoma after a UUCyt was high (33.9%) with a substantial number of
      high-grade (34%) tumours, implying that a UUCyt result cannot be interpreted as
      negative for malignancy. Therefore, in these cases, the urologist must depend on
      cystoscopy to make a diagnosis.

PMID- 19583725
TI  - Lingual mucosal grafts for anterior urethroplasty: a review.
AB  - We critically reviewed recent reports of lingual mucosal grafts (LMGs) for
      substitution urethroplasty, to determine the efficacy and complications of this
      approach. Only a few centres have published the short or interim outcome of LMG
      urethroplasty. These studies dealt mainly with surgical techniques and harvesting
      LMGs, emphasizing the comparison of different intra-oral donor sites. The
      preliminary results seem to be encouraging for the safety and efficacy of LMG
      urethroplasty. When compared with other substitute materials, LMG give equally
      good results with much easier harvesting and minimal donor site morbidity. Thus,
      lingual mucosa is most likely to become an alternative to oral mucosa for
      substitution urethroplasty and longer term results of its use are awaited with
      interest.

PMID- 19583724
TI  - Are prostate needle biopsies predictive of the laterality of significant cancer
      and positive surgical margins?
AB  - OBJECTIVE: To determine whether data obtained from preoperative prostate needle
      biopsy can predict the laterality of significant cancer and positive surgical
      margins on final-specimen pathology after laparoscopic radical prostatectomy
      (LRP). PATIENTS AND METHODS: Data from 490 patients undergoing LRP by one surgeon
      were reviewed retrospectively. The demographic characteristics, intraoperative
      data and pathological results were analysed. Univariate and multivariate analyses
      were used to determine which factors before and during LRP influenced the
      positive surgical margin status. RESULTS: There was only minor agreement between
      the laterality of positive needle biopsies and laterality of any cancer and
      significant cancer on final-specimen pathology (kappa = 0.135 and 0.151,
      respectively). This was irrespective of the number of needle cores obtained or
      final-specimen Gleason grade. Similarly, the laterality of dominant cancer on
      needle biopsy had only a minor agreement with the location of positive surgical
      margins (kappa = 0.050) and fair agreement with the location of extracapsular
      extension on final-specimen pathology (kappa = 0.235). CONCLUSIONS: Preoperative
      needle biopsy data have only a minor correlation with the laterality of
      significant cancer and positive surgical margins at final pathology of LRP
      specimens. Recognition of this fact, and the frequent bilaterality of significant
      cancer, with its potential for contralateral positive surgical margins even when
      the biopsies are positive only unilaterally, is an important consideration when
      planning nerve-sparing, and potentially for focal therapy.

PMID- 19583726
TI  - Fragmentation of prostatic needle biopsy cores containing adenocarcinoma: the
      role of specimen submission.
AB  - OBJECTIVE: To determine the factors contributing to the fragmentation of
      prostatic core biopsies containing prostatic carcinoma, which might complicate
      the quantification of the number cores with cancer and/or the amount of tumour in
      a core. MATERIALS AND METHODS: Prostate biopsy cases containing fragmented cores
      with cancer and cancer cases present only in unfragmented cores were sought in
      records from the consultant service of one of the authors. A 'part' corresponded
      to the site-specific jar submitted by the urologist (i.e. left or right; left
      apex, left mid, etc.). Cases of prostatic adenocarcinoma with fragmented cores
      containing cancer (463) and cases with cancer lacking fragmented cores (200) were
      compared. RESULTS: The mean number of parts per case was 8.1 and 7.5 in the
      unfragmented and fragmented cases, respectively (not significant). The mean
      number of cores per part was significantly higher in the fragmented group than
      the unfragmented group (2.6 vs 2.1, P = 0.004). The number of parts containing
      cancer was higher in cases with fragmented cores than in cases with unfragmented
      cores (2.8 vs 1.6, P < 0.001). A higher mean Gleason score was associated with
      the cancer in fragmented cores than in unfragmented cores (6.6 vs 6.2, P <
      0.001). Multivariate regression analysis showed that fragmentation was associated
      with the number of parts with cancer (P < 0.001), cores per part (P < 0.001) and
      Gleason score (P < 0.04). CONCLUSIONS: The number of parts per case with cancer,
      number of cores submitted per part, and Gleason score contribute to the
      likelihood of fragmentation of cores containing prostatic adenocarcinoma.

PMID- 19583727
TI  - Pelvic-floor imaging using three-dimensional ultrasonography and magnetic
      resonance imaging in the long term follow-up of the bladder-exstrophy-epispadias
      complex.
AB  - OBJECTIVE: To investigate whether established pelvic floor variables can be used
      to predict the risk of uterine prolapse after surgery and to compare two
      different operative strategies, pelvic adaptation with functional reconstruction
      and an open pelvis with urinary diversion, as a congenital bony pelvis and pelvic
      floor defect predisposes females with bladder-exstrophy-epispadias complex (BEEC)
      to uterine prolapse. PATIENTS, SUBJECTS AND METHODS: We conducted a cross
      sectional study using perineal three-dimensional ultrasonography (3D-US) and
      magnetic resonance imaging (MRI) to describe pelvic floor anatomy in 19 women
      with BEEC (mean age 27.3 years) and five controls, with the outcome evaluated by
      a semi-structured interview. The analysis of 3D-US and MRI was conducted by two
      independent investigators. RESULTS: Of the 19 women with BEEC, 13 initially had a
      functional bladder reconstruction, six a urinary diversion with removal of the
      exstrophic bladder, and 12 women had closure of the pelvis either by traction
      bandage or osteotomy, and in the other seven the symphysis was not approximated.
      Four patients had a complete and one a mild uterine prolapse. After a mean follow
      up of 24 years, the mean symphyseal diastasis was 4.5 cm after symphyseal
      approximation, 9.0 cm without symphyseal approximation in BEEC and 0.49 cm in
      controls. The mean levator hiatus was 4.9 cm on 3D-US and 4.1 cm on MRI after
      symphyseal approximation, 5.9 and 7.6 cm without symphyseal approximation and 4.2
      and 3.2 cm in controls, respectively. The respective mean levator angle was 86.6
      degrees and 87.3 degrees after symphyseal approximation, 104.1 degrees and 101.3
      degrees without and 71.3 degrees and 45.5 in controls. Prolapse was statistically
      significantly more common in patients with no symphyseal approximation.
      CONCLUSION: This is the first study showing that perineal 3D-US is useful for
      pelvic floor imaging in BEEC. Established pelvic floor variables might be useful
      for predicting the risk of pelvic organ prolapse in BEEC.

PMID- 19583728
TI  - Ultrasonographic bladder measurements can replace urodynamic study for the
      diagnosis of non-monosymptomatic nocturnal enuresis.
AB  - OBJECTIVE: To compare urodynamic (UD) and ultrasonography (US)-based measurements
      for the diagnosis and follow-up of patients with non-monosymptomatic primary
      nocturnal enuresis (NMPNE). PATIENTS AND METHODS: The study included 455 enuretic
      children (282 boys and 173 girls, mean age 9.58 years) with daytime voiding
      symptoms and with more than one void per night. In healthy children the upper
      limits for US-measured bladder wall thickness are 3 and 5 mm for a full or empty
      bladder, respectively. In 419 children the results showed urodynamic signs of an
      overactive bladder (OAB) and the US-measured bladder wall was thickened. After 6
      months of antimuscarinic treatment, we re-assessed the children with US and UD;
      the relation between UD and US measurements was confirmed. After analysing these
      data, we considered the use of a new diagnostic assessment for patients with
      NMPNE. In children with a significant US measurement, i.e. a bladder wall with a
      thickness of >3 mm (full bladder) and >5 mm (empty bladder), the diagnostic
      assessment was concluded and therapy was started. We restricted the UD
      examination exclusively to those patients who either had severe intractable
      symptoms or did not respond to treatment. This new management was applied to 453
      patients with NMPNE. After the first 6 months of therapy all the patients were
      assessed with a new US study. RESULTS: In all, 343 patients (75.7%) were full
      responders, with a normal bladder wall thickness; 82 (18.1%) were partial
      responders but with no normalization of bladder wall thickness; only 28 (6.2%)
      were classified as nonresponders with a persistent thickened bladder wall.
      CONCLUSIONS: We favour a more conservative management: the UD study should be
      limited to the very few patients who either have severe intractable symptoms or
      do not respond to treatment. In our experience, the US study, which is not
      invasive, is useful for the diagnosis and follow-up of NMPNE and it is preferable
      to the UD study, which is invasive and often traumatic for children.

PMID- 19583729
TI  - Acquisition of flexible cystoscopy skills on a virtual reality simulator by
      experts and novices.
AB  - OBJECTIVE: To assess the construct validity of the URO Mentor (Simbionix Corp.,
      Cleveland, OH, USA) virtual reality training model for several variables of
      skills training in cysto-urethroscopy, addressing two research questions: (i)
      Does training on the URO Mentor significantly improve novices' performance in
      terms of time, trauma, areas inspected and Global Rating Scale (GRS) score?; (ii)
      is discrimination between different levels of expertise possible using the URO
      Mentor? METHODS: Thirty experts and 50 novices performed seven tasks on the URO
      Mentor during one training session. The first, fourth and seventh tasks were
      'test tasks' to evaluate participants' performance. The simulator recorded
      procedure time and trauma; a supervisor scored which areas were inspected and
      gave scores on the GRS. A two-way analysis of variance with repeated-measures
      test was used to analyse experts' and novices' performances, with P < 0.05
      considered to indicate statistical significance. Effect sizes (ES) were
      calculated to quantify the practical significance of the results; ES of 0.10,
      0.30, and 0.50 were considered small, medium and large, respectively. RESULTS:
      Novices' performances showed a significant improvement with large ES in time
      (linear trend of learning curve P < 0.001, ES 0.66) and mean GRS score (linear
      trend P < 0.001, ES 0.84, quadratic trend P = 0.018, ES 0.24). There was a medium
      improvement for trauma (linear trend P < 0.001, ES 0.40) and a small improvement
      in areas inspected (linear trend P = 0.032, ES 0.21). That the 95% confidence
      intervals of the measures on the first task of experts and novices did not
      coincide indicates that differentiation between experts and novices on the four
      variables measured can be achieved using the URO Mentor. CONCLUSIONS: Training on
      the URO Mentor appears to result in a medium to large improvement of novices'
      performances for time, trauma, areas inspected and GRS scores. Moreover,
      discrimination between different levels of expertise is possible using this
      simulator.

PMID- 19583730
TI  - Dicoumarol enhances doxorubicin-induced cytotoxicity in p53 wild-type urothelial
      cancer cells through p38 activation.
AB  - OBJECTIVE: To investigate the effectiveness of a combined treatment of 3-30
      methylene-bis[4-hydroxycoumarin] (dicoumarol) with doxorubicin for the treatment
      of urothelial cancer, as doxorubicin is a common chemotherapeutic agent but its
      therapeutic efficacy is limited. MATERIALS AND METHODS: The synergistic effect of
      dicoumarol with chemotherapeutic agents such as cisplatin, doxorubicin and
      paclitaxel was evaluated in RT112 urothelial cancer cells. Then, dicoumarol
      mediated enhancement of doxorubicin-induced cytotoxicity was screened in
      urothelial cancer cell lines with different p53 statuses or RT112 stable
      transfectants with a dominant-negative mutant of p53 (p53DN). To clarify the
      importance of the modification of p53 function by dicoumarol to enhance
      doxorubicin toxicity, the change in the p53-p21 pathway and mitogen-activated
      protein kinase (MAPK)-mitochondria pathway by the combined treatment were
      elucidated by Western blot analysis. Finally, the effect of p21 knockdown in the
      susceptibility to doxorubicin was examined with RT112 stable transfectants with
      short hairpin RNA (shRNA) of p21. RESULTS: Dicoumarol significantly increased the
      susceptibility of RT112 cells to cisplatin and doxorubicin, but not to paclitaxel
      in RT112 cells. Dicoumarol (100 microm) also enhanced the cytotoxicity of
      doxorubicin in other bladder cancer cell lines with wild-type p53 (wt-p53; three
      times in 253J and 13 times in KK47), but not in those with mutant-type p53
      (TCCsup, J82 and EJ) or in RT112 p53DN. The combined treatment with dicoumarol
      suppressed p53/p21 induction by doxorubicin and resulted in sequential p38 MAPK
      activation, myeloid cell leukaemia 1 suppression and caspase cleavage. The
      synergistic effect of doxorubicin/dicoumarol was suppressed by the p38 MAPK
      inhibitor SB202190 and, furthermore, p21 knockdown with shRNA transfection made
      RT112 cells six times more susceptible to doxorubicin with p38 MAPK activation.
      CONCLUSION: These results suggest that concomitant use of dicoumarol could
      enhance the cytotoxicity of doxorubicin in urothelial cancer cells with wt-p53
      through the p53/p21/p38 MAPK pathways. This combined treatment may provide a new
      therapeutic option to overcome chemoresistance in bladder cancer.

PMID- 19583731
TI  - Robot-assisted radical prostatectomy in men aged > or =70 years.
AB  - OBJECTIVES: To assess the outcomes of elderly men with prostate cancer treated
      with robot-assisted radical prostatectomy (RARP), because more healthy elderly
      men will present with localized prostate cancer and many will seek surgical
      treatment as the population ages. PATIENTS AND METHODS: Between 2005 and 2008,
      203 men had RARP performed by one surgeon; patients were categorized into two
      groups based on their age (> or =70 vs <70 years). All data were recorded
      prospectively in an institutional approved database. RESULTS: Of the 203 men, 23
      (11%) were aged > or =70 years; the older men had similar baseline
      characteristics as younger men, and had characteristics during and after surgery
      comparable to those in younger men. The pathological RARP Gleason grade was
      significantly greater in older men. Surgical complications were not significantly
      different between the groups. Continence rates were significantly lower in older
      men at 6 months after surgery, but returned to levels equivalent to those in
      younger men within 12 months after surgery. Older patients took significantly
      longer to be capable of driving after surgery. CONCLUSIONS: The outcomes of RARP
      in elderly men are largely comparable to those in younger men, with the exception
      of higher pathological Gleason grade, a transient delay in return of continence,
      and taking longer to return to driving after surgery. Advanced chronological age
      should not be a contraindication for RARP in patients with clinically localized
      prostate cancer, but expectations should be managed preoperatively.

PMID- 19583732
TI  - Obesity is associated with a higher risk of clear-cell renal cell carcinoma than
      with other histologies.
AB  - OBJECTIVE: To investigate the association between body mass index (BMI) and
      histology of renal cell carcinoma (RCC) in a contemporary cohort, as obesity is
      increasingly prevalent in the USA and might be contributing to the increasing
      incidence of RCC, but little is known about the relationship of obesity with the
      different histological subtypes of RCC. PATIENTS AND METHODS: From January 2000
      to December 2007 we identified 1640 patients with renal cortical tumours
      undergoing surgical extirpation at our institution, and who had their BMI
      recorded. Multivariable logistic regression models were used to test the
      association of BMI with RCC histology. RESULTS: The median (interquartile range)
      BMI was 28 (25-32) kg/m(2) and 38% of patients were classified as obese (BMI >30
      kg/m(2)). After adjusting for tumour size, age, gender, American Society of
      Anesthesiologists score, estimated glomerular filtration rate, hypertension,
      diabetes mellitus and smoking, the BMI was significantly associated with clear
      cell histology; the odds ratios were 1.04 for each unit of BMI (95% confidence
      interval, CI, 1.02-1.06; P < 0.001) and 1.48 when comparing obese vs non-obese
      patients (95% CI 1.19-1.84; P < 0.001). In the subgroup of patients with RCC
      (excluding benign renal cortical tumours), BMI was still an independent predictor
      of clear-cell histology (odds ratio 1.04, 95% CI 1.02-1.06, P = 0.001).
      CONCLUSIONS: These results suggest that BMI is an independent predictor of clear
      cell histology in patients with a renal cortical tumour. While the aetiology of
      this phenomenon requires further study, these findings might have implications in
      determining a patient's risk of harbouring a clear-cell RCC and in subsequent
      treatment recommendations.

PMID- 19583733
TI  - Compartment syndrome in urological practice.

PMID- 19583734
TI  - Expression of vascular endothelial growth factor and angiopoietins in human
      corpus cavernosum.
AB  - OBJECTIVE: To evaluate the expression of the angiogenic factors vascular
      endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human
      penile erectile tissue. MATERIALS AND METHODS: Penile fragments were removed from
      four young healthy organ donors (aged 17-28 years), and processed for
      immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors
      (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm
      the expression of VEGF and Angs in erectile tissue. RESULTS: VEGF and VEGFR1
      expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected
      mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a
      scattered distribution mostly in the perivascular SM layer, showing co
      localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2
      was not detected by immunohistochemical studies, but the use of the same antibody
      in molecular analysis confirmed Ang2 expression in human corpus cavernosum.
      CONCLUSIONS: We show for the first time the co-localization of VEGF and Ang1 in
      the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be
      available for neoangiogenesis, if challenged. Studies of endothelial markers,
      growth factors and specific receptors are useful for understanding vascular
      organization and angiogenesis in normal human erectile tissue. This knowledge
      will be fundamental for developing newer therapeutic approaches to prevent or
      even cure erectile dysfunction.

PMID- 19583735
TI  - Epibulbar complex choristoma and hemimegalencephaly in linear sebaceous naevus
      syndrome.
AB  - Epidermal naevus syndrome is a group of congenital syndromes comprising epidermal
      naevi associated with a variety of developmental abnormalities of the ocular,
      nervous, skeletal, cardiovascular and urogenital systems. We describe a case of
      an 8-month-old boy with a brown alopecic plaque on his face and scalp and a
      vascularized epibulbar mass involving the entire cornea, which had been present
      since birth. Histopathological examination identified sebaceous naevus in
      combination with complex choristoma. Magnetic resonance imaging of the brain
      showed hemimegalencephaly.

PMID- 19583736
TI  - Weathering of the hairless scalp: a study using skin capacitance imaging and
      ultraviolet light-enhanced visualization.
AB  - The balding scalp is particularly exposed to sunlight, hence, the overall ageing
      process modulated by ultraviolet and near-infrared light may be increased at this
      location. The induced changes are better revealed under ultraviolet light
      examination. Any alteration in the epidermal maturation is potentially reflected
      by stratum corneum changes observed as disturbances on skin-capacitance imaging.

PMID- 19583737
TI  - Permanent makeup removal using Q-switched Nd:YAG laser.
AB  - Red-brown tattoos are usually treated with a frequency-doubled Q-switched (QS)
      neodymium:yttrium-aluminum-garnet Nd:YAG laser (532 nm), because red and pink
      pigments show maximum absorption between 500 and 570 nm. Using a QS laser for red
      brown tattoo removal has sometimes led to paradoxical darkening of the tattoo
      pigments, and this darkened grey-black colour may be difficult to remove. A woman
      with red-brown cosmetic tattoos on her eyebrows was treated using a QS Nd:YAG
      laser (1064 nm) initially with low fluence and subsequently with increasing
      fluences at 6-weekly intervals. After the first treatment, a slight darkening of
      the tattoo pigments was seen, but this faded and complete clearance was achieved
      after five treatments. There was no downtime during every treatment and there
      were no scars, pigmentary alterations or textural changes.

PMID- 19583738
TI  - Development of motor speed and associated movements from 5 to 18 years.
AB  - AIM: To study the development of motor speed and associated movements in
      participants aged 5 to 18 years for age, sex, and laterality. METHOD: Ten motor
      tasks of the Zurich Neuromotor Assessment (repetitive and alternating movements
      of hands and feet, repetitive and sequential finger movements, the pegboard,
      static and dynamic balance, diadochokinesis) were administered to 593 right
      handed participants (286 males, 307 females). RESULTS: A strong improvement with
      age was observed in motor speed from age 5 to 10, followed by a levelling-off
      between 12 and 18 years. Simple tasks and the pegboard matured early and complex
      tasks later. Simple tasks showed no associated movements beyond early childhood;
      in complex tasks associated movements persisted until early adulthood. The two
      sexes differed only marginally in speed, but markedly in associated movements. A
      significant laterality (p<0.001) in speed was found for all tasks except for
      static balance; the pegboard was most lateralized, and sequential finger
      movements least. Associated movements were lateralized only for a few complex
      tasks. We also noted a substantial interindividual variability. INTERPRETATION:
      Motor speed and associated movements improve strongly in childhood, weakly in
      adolescence, and are both of developmental relevance. Because they correlate
      weakly, they provide complementary information.

PMID- 19583739
TI  - Childhood chorea-encephalopathy and unremarkable MRI: an association suggesting
      parvovirus B19 infection.

PMID- 19583740
TI  - Selection and assessment of children with Developmental Coordination Disorder.

PMID- 19583741
TI  - HIV-stage, nutritional status, and child psychomotor development in resource-poor
      settings - a causal web.

PMID- 19583742
TI  - Repeat botulinum toxin-A injections in the upper limb of children with
      hemiplegia: a randomized controlled trial.
AB  - AIM: To test the effectiveness of repeat botulinum toxin A (BoNT-A) injections in
      the affected arm of 22 children with hemiplegic cerebral palsy (19 males, three
      females), aged 1 year 10 months to 4 years 10 months (mean 3y 8mo, SD 9mo) in a
      randomized controlled trial. METHOD: Children received either three series of
      BoNT-A injections plus twice-weekly occupational therapy (OT) or OT alone in 16
      week cycles. Muscles targeted at each injection cycle in the 11 children
      receiving BoNT-A+OT were the adductor pollicis (n=9), flexor pollicis longus
      (n=5), flexor digitorum superficialis (n=8), flexor digitorum profundus (n=8),
      flexor carpi radialis (n=2), flexor carpi ulnaris (n=6), pronator teres (n=10),
      and biceps brachii (n=11). Parental perception of treatment efficacy was assessed
      using the Canadian Occupational Performance Measure (COPM) and the Goal
      Attainment Scale (GAS), quality of movement using the Quality of Upper Extremity
      Skills Test (QUEST), fine motor skills using the Peabody Developmental Motor
      Scale - Fine Motor (PDMS-FM), and spasticity using the Modified Tardieu Scale
      (MTS). Between-group differences at 12 months were analysed using independent
      sample t-tests. RESULTS: All children were at Gross Motor Function Classification
      System levels I (BoNT-A+OT n=6; OT n=8) or II (n=5 and n=3 respectively) and were
      too young to be classified using the Manual Ability Classification System. The
      BoNT-A+OT group had higher COPM performance scores (mean difference -0.8, 95%
      confidence interval [CI] -1.5-0.0) and higher GAS T scores (mean difference -6.9,
      95% CI -13.8 to -0.1]). No significant difference was found for the COPM
      satisfaction, PDMS-FM, or QUEST scores. The BoNT-A+OT group showed progressive
      reduction in spasticity compared with the OT group. At study completion MTS mean
      difference was 50.0 degrees (95% CI 22.4-77.6) for pronators and 20.9 degrees
      (95% CI 2.4-39.4) for wrist flexors. INTERPRETATION: Repeat BoNT-A injections in
      the upper limb combined with OT resulted in progressively reduced spasticity and
      improved parental perception of performance.

PMID- 19583743
TI  - Presumed perinatal stroke in a child with Down syndrome and moyamoya disease.
AB  - Moyamoya disease describes a cerebral arteriopathy characterized by stenosis or
      occlusion of the terminal internal carotid and/or the proximal middle cerebral
      arteries. We report a female child with trisomy 21 and bilateral moyamoya disease
      who presented, unusually, with a presumed perinatal cerebral infarct. The
      clinical, radiological, and angiographic features of moyamoya disease in children
      with Down syndrome are similar to those with other aetiologies or idiopathic
      cases. Early recognition is important as moyamoya disease presenting in childhood
      is associated with a high rate of recurrent stroke and there is evidence that
      surgical revascularization can prevent further events. An important practical
      lesson arising from this case is that although the evaluation of children with
      presumed perinatal stroke tends to be limited relative to the evaluation of
      arterial ischaemic stroke in older children, this may need to be more
      comprehensive in infants at high risk of arteriopathy. The parents of the child
      gave informed consent to the publication of this report.

PMID- 19583744
TI  - Longitudinal development of hand function in children with unilateral cerebral
      palsy.
AB  - AIM: The aim of this study was to describe how the usefulness of the hemiplegic
      hand develops in children with unilateral cerebral palsy (CP) aged between 18
      months and 8 years. METHOD: A prospective longitudinal study of 43 children (22
      males, 21 females) with unilateral CP was conducted. Inclusion age was 18 months
      to 5 years 4 months (mean 2y 8mo [SD 1y 1mo]). Children were assessed with the
      Assisting Hand Assessment (AHA) 3 to 11 times per child over a mean period of 4
      years 6 months. Two models were used for grouping children: by AHA score at 18
      months and by Manual Ability Classification System (MACS) levels. Estimated
      average motor development curves were fitted with a nonlinear mixed-effects
      model. RESULTS: Children with a high AHA score (high ability level) at 18 months
      reached a significantly higher ability level and at a higher progression rate
      than children with a low 18-month AHA score. Limits of development differed
      between the three MACS levels. INTERPRETATION: Results indicate that the AHA
      score at 18 months can be used to discuss future development of affected hand use
      in bimanual tasks in children with unilateral CP.

PMID- 19583745
TI  - Hip displacement and scoliosis in Rett syndrome - screening is required.
AB  - AIM: This study aimed to determine the prevalence of hip displacement and spinal
      deformity in a clinic population of females with Rett syndrome to define
      implications for screening and management. METHOD: Age, MECP2 gene status, gross
      motor function, prevalence of hip displacement, as measured by migration
      percentage, and spinal deformity, determined by measurement of Cobb angle, were
      recorded. RESULTS: Thirty-one females with a mean age of 15 years 6 months (SD 5y
      4mo) fulfilled a clinical diagnosis of Rett syndrome. Fifteen (48%, 95%
      confidence interval [CI] 30-67) of the cohort had a hip migration percentage of
      30% of more. Eight of the 31 patients (95% CI 12-45) had undergone surgery for
      the prevention or treatment of hip displacement or dislocation. Twenty-seven of
      the 31 patients (95% CI 70-96) had a scoliosis, with a Cobb angle of less than 10
      degrees; 20 patients (95% CI 45-81) had a Cobb angle greater than 30 degrees.
      Eleven (95% CI 19-55) patients have required spinal fusion surgery.
      INTERPRETATION: The prevalence of hip displacement and spinal deformity in a
      clinic cohort of females with Rett syndrome in Victoria, Australia, was very
      high. Early, repeated, and consistent clinical and radiological surveillance for
      hip displacement and spinal deformities is recommended in all young patients with
      Rett syndrome.

PMID- 19583746
TI  - The cholinesterase inhibitor physostigmine for the local treatment of dry mouth:
      a randomized study.
AB  - Application of physostigmine to the oromucosal surface with the aim of
      stimulating underlying mucin-producing glands while reducing cholinergic systemic
      effects might be a strategy for treating dry mouth. Subjects suffering from dry
      mouth and with hyposalivation participated in a crossover, double-blind,
      randomized study. A gel containing physostigmine (0.9, 1.8, 3.6, and 7.2 mg) or
      placebo was applied to the inside of the lips and distributed with the tongue.
      The feeling of dryness was assessed using a visual analogue scale (VAS) (where a
      score of 100 = extremely dry) and systemic effects were registered. Based on
      assessments of efficacy and safety, the dose of 1.8 mg of physostigmine was
      selected for use in the second part of the study to make objective measurements
      of saliva volumes. Physostigmine (1.8 mg) produced long-lasting (120 min) relief
      (evident as a score reduction of 25 on the VAS) in the feeling of dryness.
      Judging from AUC values related to baseline over 180 min, the improvement for
      both mouth and lips in response to physostigmine was six times greater than that
      to placebo. At higher doses of physostigmine, gastrointestinal discomfort
      predominantly occurred. The volume of saliva collected in response to
      physostigmine was five times higher over 180 min than that collected in response
      to placebo. Physostigmine, applied locally, therefore appears to be a promising
      modality for dry-mouth treatment.

PMID- 19583747
TI  - Effects of amphetamine on salivary secretion.
AB  - Amphetamine induces xerogenic effects, but its mechanism of action and xerogenic
      potency are unknown. In the current in vivo study on the rat parotid gland, the
      effects of amphetamine on reflex-evoked and acetylcholine-evoked salivation were
      examined in the absence and presence of adrenergic and dopaminergic antagonists.
      Under anaesthesia, amphetamine increased the secretion of salivary fluid and the
      amount of protein therein in response to acetylcholine. Phentolamine abolished
      the increase in salivary flow and had no effect on the salivary protein
      concentration, whereas propranolol only reduced the salivary protein
      concentration. Reflex activation of the secretion evoked a well-maintained level
      of secretion that was reduced by amphetamine [50% inhibitory dose (ID(50)) 1.9 +/
      0.1 mg kg(-1) intravenously); the salivary protein concentration was increased
      in the presence of amphetamine. Phentolamine and haloperidol reduced the
      amphetamine-inhibitory effect on the reflex-evoked fluid response, whereas
      propranolol had no effect on the fluid response. The xerogenic effect of
      amphetamine is mainly exerted by central mechanisms involving alpha
      adrenoceptors, while, indirectly, amphetamine causes secretion of protein by
      inducing the release of noradrenaline from glandular nerve terminals.

PMID- 19583748
TI  - Redistribution of small GTP-binding protein, Rab27B, in rat parotid acinar cells
      after stimulation with isoproterenol.
AB  - Small GTP-binding protein, Rab27, has been implicated in the regulation of
      different types of membrane trafficking, including melanosome transport in
      melanocytes and regulated secretion events in a wide variety of secretory cells.
      We have previously shown that Rab27 is involved in the control of isoproterenol
      (IPR)-induced amylase release from rat parotid acinar cells. Although Rab27 is
      predominantly localized on secretory granules under resting conditions, changes
      to its intracellular localization after beta-stimulation have never been
      elucidated. The present study investigated IPR-induced redistribution of Rab27B
      in the parotid acinar cells, revealing translocation from secretory granules to
      the subapical region after 5 min of IPR treatment and then diffusion into the
      cytosol after 30 min of IPR treatment. Dissociation of Rab27B from the apical
      plasma membrane is probably mediated through the Rab GDP dissociation inhibitor
      (GDI) in the cytosol extracting GDP-bound Rab protein from membranes, as a
      dramatic increase in the amount of the Rab27B-GDI complex in the cytosol was
      observed 30 min after stimulation with IPR. These results indicate that, in
      parotid acinar cells, Rab27B is translocated, in a time-dependent manner, from
      secretory granules into the apical plasma membrane as a result of exposure to
      IPR, and then into the cytosol through binding with the GDI.

PMID- 19583749
TI  - Genomic instability and tumor-specific DNA alterations in oral leukoplakias.
AB  - Leukoplakias, clinically identifiable premalignant lesions, often precede oral
      squamous cell carcinoma (OSCC). Identification of leukoplakias that have the
      potential for transformation to malignancy is a key clinical problem. The aim of
      this study was to assess genomic instability, and to detect tumor-specific
      genomic alterations, in leukoplakias. Genomic instability was analyzed by
      comparing the DNA fingerprints of 32 leukoplakias with those of paired normal
      tissue. In addition, the mutational status of the p53 gene was analyzed using
      polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP)
      and polymerase chain reaction-heteroduplex DNA (PCR-HET), and the mutations were
      subsequently confirmed by DNA sequencing. Moderate-to-significant genomic
      instability was detected in all leukoplakias analysed. Nine unique amplicons,
      present in leukoplakias but not in normal tissue, were retrieved and successfully
      characterized. The p53 gene was mutated in 40.6% of patients. Four patients with
      moderate instability and mutated p53 developed OSCC. The data obtained in this
      study support and concretize the thesis that premalignant lesions possess many of
      the alterations found in cancer before the development of a malignant phenotype.
      Inactivation or mutation of the p53 tumor-suppressor might be an early event
      contributing to genomic instability and increasing the risk of malignant
      transformation.

PMID- 19583750
TI  - Reduction of orthodontic tooth movement by experimentally induced periodontal
      inflammation in mice.
AB  - Orthodontic therapy is known to have an aggravating effect on the progression of
      destructive periodontitis if oral hygiene is not maintained. However, it is
      largely unknown how active periodontitis affects the velocity of orthodontic
      tooth movement. In this study, we examined the effect of periodontal inflammation
      on orthodontic tooth movement using a mouse model. Orthodontic force was applied
      on the maxillary first molar of mice, with or without ligature wire to induce
      experimental periodontitis. The distance moved by the first molar was
      significantly reduced by the ligature-induced experimental periodontitis.
      Tartrate-resistant acid phosphatase staining revealed that the number of
      osteoclasts present during orthodontic treatment was lower in the pressure zone
      of alveolar bone in the presence of periodontal inflammation. Consistently, the
      expression level of receptor activator of nuclear factor-kappaB ligand (RANKL) in
      the pressure zone was decreased in the ligature group. By contrast, experimental
      periodontitis increased the expression of cyclooxygenase-2 mRNA in the
      periodontal tissues, while in vitro treatment with prostaglandin E(2) decreased
      extracellular signal-regulated kinase phosphorylation and RANKL expression
      induced by mechanical stress in osteoblasts. Taken together, these results
      suggest that the orthodontic force-induced osteoclastogenesis in alveolar bone
      was inhibited by the accompanying periodontal inflammation, at least partly
      through prostaglandin E(2), resulting in reduced orthodontic tooth movement.

PMID- 19583751
TI  - Healing of extraction sockets in collagenase-2 (matrix metalloproteinase-8)
      deficient mice.
AB  - Matrix metalloproteinase-8 (MMP-8) participates in skin wound healing and
      inflammation. We hypothesized that MMP-8 plays a role in wound healing after
      tooth extraction and in periapical inflammation. Bone formation, collagen
      metabolism, and inflammation in tooth extraction socket and in periapical lesions
      were analyzed in wild-type mice and in MMP-8-deficient (MMP-8(-/-)) mice. New
      trabecular bone area in the extraction sockets and in periapical lesions were
      similar in both groups. In extraction sockets significantly more type III
      procollagen was synthesized, and the neutrophil and MMP-9 levels were lower in
      MMP-8(-/-) mice. The amount of Fas ligand, identified as a substrate for MMP-8,
      was lower in alveolar mucosa but higher in alveolar bone of MMP-8(-/-) mice.
      These results indicate that MMP-8 can modulate inflammation and collagen
      metabolism of alveolar bone and mucosa.

PMID- 19583752
TI  - Effects of toothbrushing force on the mineral content and demineralized organic
      matrix of eroded dentine.
AB  - Eroded dentine has a complex histological structure, and its organic fraction
      becomes increasingly exposed as a result of the continual action of acids. The
      present study sought to investigate the effects of brushing forces up to 4 N on
      mineralized and organic dentine fractions. The study was a cyclic
      demineralization and remineralization experiment (carried out over 9 d). Erosion
      was performed with HCl (6 x 2 min d-1), pH 1.6. Samples exposed to erosion alone
      served as controls; test samples were eroded and brushed with a powered
      toothbrush (2 x 15 s d-1), applying forces of 2, 3, or 4 N. Samples were analysed
      (using profilometry and longitudinal microradiography) before and after the
      removal of superficial organic material with collagenase. Randomly selected
      samples were subjected to scanning electron microscopy. Demineralized organic
      material was present on all samples regardless of brushing force. Loss values
      (determined using profilometry) after erosion only, and after brushing with
      forces of 2, 3, and 4 N, were 11.7 +/- 5.1, 13.6 +/- 11.2, 30.7 +/- 19.0, and
      25.5 +/- 20.3, respectively, before treatment with collagenase, and 111.7 +/-
      11.6, 122.0 +/- 11.8, 121.9 +/- 15.7, and 123.0 +/- 12.0, respectively, after
      treatment with collagenase. Microradiography confirmed the results. Significant
      effects of brushing force were only found on the demineralized organic fraction,
      and mineral loss was unaffected. The notion that eroded dentine is particularly
      prone to abrasion should be reconsidered.

PMID- 19583753
TI  - Prevalence of halitosis in the population of the city of Bern, Switzerland: a
      study comparing self-reported and clinical data.
AB  - Epidemiological data on halitosis are rare. In this study we evaluated the
      prevalence of halitosis in the population of the city of Bern, Switzerland, using
      a standardized questionnaire and clinical examination. First of all, a
      standardized questionnaire was filled out by all 419 participants. In the
      clinical examination, 'objective' values for halitosis were gathered through two
      different organoleptic assessments and by the measurement of volatile sulfur
      compounds (VSC). Additionally, tongue coating and the modified periodontal
      screening index (PSI) were evaluated for each participant. The questionnaire
      revealed that 32% of all subjects sometimes or often experienced halitosis. The
      organoleptic evaluation (grade 0-5) identified 48 persons with grade 3 and
      higher. Measurement of VSC identified 117 subjects (28%) with readings of >or= 75
      parts per billion (ppb). Tongue coating, modified PSI, and smoking were
      significantly associated with higher organoleptic scores, and tongue coating and
      smoking were associated with higher VSC values. For about one-third of the
      Bernese city population, halitosis seems to pose an oral health problem. Only a
      weak correlation between self-reported halitosis and either organoleptic or VSC
      measurements could be detected.

PMID- 19583754
TI  - Dental fear and subjective oral impacts among adults in Finland.
AB  - We aimed to study the association between subjective oral impacts and dental fear
      adjusted for age, gender, level of education, and dental attendance, and to
      evaluate whether this association was modified by the number of remaining teeth.
      Nationally representative data on Finnish adults, 30+ yr of age (n = 5,987), were
      gathered through interviews, clinical examination, and questionnaires. Dental
      fear was measured using the question: 'How afraid are you of visiting a dentist?'
      and subjective oral impacts were measured using the 14-item Oral Health Impact
      Profile (OHIP-14) questionnaire. The outcome variables were the percentage of
      people reporting one or more OHIP-14 items fairly often or very often, and the
      'extent' and 'severity'. Those with high dental fear reported higher levels of
      prevalence, 'extent', and 'severity' of subjective oral impacts than did those
      with low dental fear or no fear. The association between dental fear and
      subjective oral impacts was not significantly modified by the number of remaining
      teeth. The greatest differences between those with high dental fear and low
      dental fear were found in psychological, social, and handicap dimensions, but not
      in functional or physical dimensions of the OHIP-14. Treating dental fear could
      have positive effects on subjective oral impacts by reducing psychological and
      social stress and by improving regular dental attendance and oral health.

PMID- 19583755
TI  - Young children's Oral Health-Related Quality of Life and dental fear after
      treatment under general anaesthesia: a randomized controlled trial.
AB  - During the past decade the research interest in Oral Health-Related Quality of
      Life (OHRQoL) has been prospering. This study was performed to test (using a
      randomized controlled trial design) the hypothesis that young children's OHRQoL
      improves after oral rehabilitation under general anaesthesia (GA). A further aim
      of this study was to explore whether dental fear also changes. One-hundred and
      four children (54 boys; mean age 4.08 yr, standard deviation = 1.09), who had
      been referred to a specialized clinic in paediatric dentistry, were randomly
      assigned, based on a Solomon four-group design, to two treatment (GA) and two
      control conditions. The Early Childhood Oral Health Impact Scale (ECOHIS) and the
      Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) were used to assess
      OHRQoL and dental fear, respectively, before and after the rehabilitation
      procedures. A 2 x 2 analysis of variance revealed that the total ECOHIS score
      after GA was more positive in the GA group than in the control group. There was
      no effect found of the pre-test and there was also no interaction between the pre
      test and treatment. In the total CFSS-DS scores no effects were found. The
      results of this study showed that the child's OHRQoL improved after treatment
      under GA. Furthermore, children need guidance in reducing dental fear after
      treatment under GA.

PMID- 19583756
TI  - One- vs. five-session treatment of intra-oral injection phobia: a randomized
      clinical study.
AB  - The present study aimed to evaluate the effect of one and five sessions of
      treatment for intra-oral injection phobia in 55 subjects fulfilling the DSM-IV
      criteria for specific phobia. The subjects were randomly assigned to one or five
      sessions of cognitive behavioural therapy (CBT) performed by dentists.
      Assessments included behavioural tests and self-report instruments used
      pretreatment, post-treatment, and at 1 yr of follow-up. The dental anxiety scale
      (DAS), the injection phobia scale-anxiety, and the mutilation questionnaires were
      applied. Mean avoidance duration of intra-oral injections before treatment was
      7.0 yr. The results showed that 89% of the subjects had received intra-oral
      injections from a regular dentist during the 1-yr follow-up. The only significant
      difference between the one- and the five-session groups was that the five-session
      group reported less anxiety (as measured using the DAS) at 1 yr of follow-up. It
      was concluded that both treatments performed by dentists specially trained in CBT
      have a significant treatment effect on the intra-oral injection phobia.

PMID- 19583757
TI  - The impact of educational level on oral health-related quality of life in older
      people in London.
AB  - There are socioeconomic inequalities in oral health, but the relationship between
      education and oral health-related quality of life (OHRQoL) among older adults has
      not been adequately studied. This study assessed whether there is an educational
      gradient in OHRQoL among older people in London. We employed secondary analysis
      of baseline data (n = 1,090) from a randomized controlled trial of health-risk
      appraisal on community-dwelling non-disabled people 65 yr of age and older,
      registered with three group medical practices in suburban London. Multiple linear
      regressions were used to analyze the association between OHRQoL [measured using
      the Geriatric Oral Health Assessment Index (GOHAI)] and education, adjusted for
      age, gender, pension status, and denture wearing. Overall, 30.6% reported low
      levels of OHRQoL. Eating discomfort was the most frequent problem (24% reported
      'often/always'), while concerns about appearance were also prevalent. Significant
      variations in OHRQoL existed between socioeconomic groups. In adjusted analyses,
      there was a clear education gradient in OHRQoL, with worse perceptions at each
      lower level of education. Low educational level has an independent negative
      impact on OHRQoL in older people, which is not explained by differences in income
      or in denture wearing between educational groups. Policies targeting lower
      educated groups should be complemented with whole-population strategies for the
      reduction of oral health inequalities.

PMID- 19583758
TI  - Factorial structure and cross-cultural invariance of the Oral Impacts on Daily
      Performances.
AB  - The issue of cross-cultural construct validation and measurement invariance of
      the Oral Impacts on Daily Performances (OIDP) questionnaire is important. Using
      confirmatory factor analysis (CFA), this study evaluated a proposed three-factor
      structure of the OIDP questionnaire in Tanzanian adolescents and adults and
      assessed whether this model would be replicated in Ugandan adolescents. Between
      2004 and 2007, OIDP data were collected from 1,601 Tanzanian adolescents, 1,031
      Tanzanian adults, and 1,146 Ugandan adolescents. Model generation analysis was
      restricted to Tanzanian adolescents, and the model achieved was tested, without
      modification, in Tanzanian adults and in Ugandan adolescents. A modified three
      factor solution with cross-loadings improved the fit of the OIDP model to the
      data compared with a one-factor model and the original three-factor model within
      the Tanzanian [comparative fit index (CFI) = 0.99] and Ugandan (CFI = 0.98)
      samples. Cross-validation in Tanzanian adults provided a reasonable fit (CFI =
      0.98). Multiple-group CFA demonstrated acceptable fit [chi(2) = 140.829, degrees
      of freedom (d.f.) = 24, CFI = 0.98] for the unconstrained model, whereas
      unconstrained and constrained models were statistically significantly different.
      Factorial validity was confirmed for the three-factor OIDP model. The results
      provide evidence for cross-cultural equivalence of the OIDP, suggesting that this
      measure is comparable, at least to some extent, across Tanzanian and Ugandan
      adolescents.

PMID- 19583759
TI  - A comparison between two-dimensional and three-dimensional cephalometry on
      frontal radiographs and on cone beam computed tomography scans of human skulls.
AB  - The aim of this study was to evaluate whether measurements performed on
      conventional frontal radiographs are comparable to measurements performed on
      three-dimensional (3D) models of human skulls derived from cone beam computed
      tomography (CBCT) scans and if the latter can be used in longitudinal studies.
      Cone beam computed tomography scans and conventional frontal cephalometric
      radiographs were made of 40 dry human skulls. From the CBCT scan a 3D model was
      constructed. Standard cephalometric software was used to identify landmarks and
      to calculate ratios and angles. The same operator identified 10 landmarks on both
      types of cephalometric radiographs, and on all images, five times with a time
      interval of 1 wk. Intra-observer reliability was acceptable for all measurements.
      There was a statistically significant and clinically relevant difference between
      measurements performed on conventional frontal radiographs and on 3D CBCT-derived
      models of the same skull. There was a clinically relevant difference between
      angular measurements performed on conventional frontal cephalometric radiographs,
      compared with measurements performed on 3D models constructed from CBCT scans. We
      therefore recommend that 3D models should not be used for longitudinal research
      in cases where there are only two-dimensional (2D) records from the past.

PMID- 19583760
TI  - The effect of a peroxidase primer on bond strength of three luting systems to
      dentin.
AB  - The purpose of the present study was to investigate the effect of an experimental
      primer containing a microperoxidase (MP-11) with 2-hydroxyethyl methacrylate on
      adhesive bonding of three different luting systems and dentin. The luting systems
      prepared were three etch-and-rinse systems (10-3/Super-Bond, 10-0/Super-Bond,
      65PA/Super-Bond), a self-etching system (PanaviaF2.0), and a self-adhesive system
      (SA-Luting). These luting systems were used in conjunction with the MP-11 primer,
      and were designated as 10-3/MP-11/Super-Bond, 10-0/MP-11/Super-Bond, 65PA/MP
      11/Super-Bond, MP-11/PanaviaF2.0, MP-11/SA-Luting, respectively. The dentin
      surfaces of human premolar teeth were treated, and then bonded with acrylic rods.
      Shear bond strengths were determined after 24 h of storage in water. The maximum
      mean bond strength was obtained with 10-0/MP-11/Super-Bond (48.7 +/- 6.6 MPa),
      followed by 10-3/MP-11/Super-Bond (36.3 +/- 10.2 MPa), 65PA/MP-11/Super-Bond
      (32.9 +/- 9.2 MPa), 10-3/Super-Bond (26.6 +/- 6.7 MPa), MP-11/PanaviaF2.0 (21.4
      +/- 5.6 MPa), MP-11/SA-Luting (17.2 +/- 3.5 MPa), PanaviaF2.0 (16.9 +/- 5.7 MPa),
      65PA/Super-Bond (12.8 +/- 2.0 MPa), SA-Luting (11.2 +/- 5.4 MPa), and 10-0/Super
      Bond (9.6 +/- 3.9 MPa). The additional use of MP-11 primer significantly improved
      the bond strengths in the etch-and-rinse systems with 4-META/MMA-TBB resin. It is
      suggested that the peroxidase has a potential to improve dentin adhesion in the
      etch-and rinse, self-etching, and self-adhesive systems.

PMID- 19583761
TI  - Load-bearing capacity of all-ceramic posterior inlay-retained fixed dental
      prostheses.
AB  - The purpose of this in vitro study was to compare the quasi-static load-bearing
      capacity of all-ceramic resin-bonded three-unit inlay-retained fixed dental
      prostheses (IRFDPs) made from computer-aided design/computer-aided manufacturing
      (CAD/CAM)-manufactured yttria-stabilized tetragonal zirconia polycrystals (Y-TZP)
      frameworks with two different connector dimensions, with and without fatigue
      loading. Twelve IRFDPs each were made with connector dimensions 3 x 3 mm(2)
      (width x height) (control group) and 3 x 2 mm(2) (test group). Inlay-retained
      fixed dental prostheses were adhesively cemented on identical metal-models using
      composite resin cement. Subgroups of six specimens each were fatigued with
      maximal 1,200,000 loading cycles in a chewing simulator with a weight load of 25
      kg and a load frequency of 1.5 Hz. The load-bearing capacity was tested in a
      universal testing machine for IRFDPs without fatigue loading and for IRFDPs that
      had not already fractured during fatigue loading. During fatigue testing one
      IRFDP (17%) of the test group failed. Under both loading conditions, IRFDPs of
      the control group exhibited statistically significantly higher load-bearing
      capacities than the test group. Fatigue loading reduced the load-bearing capacity
      in both groups. Considering the maximum chewing forces in the molar region, it
      seems possible to use zirconia ceramic as a core material for IRFDPs with a
      minimum connector dimension of 9 mm(2). A further reduction of the connector
      dimensions to 6 mm(2) results in a significant reduction of the load-bearing
      capacity.

PMID- 19583762
TI  - Marginal accuracy of four-unit zirconia fixed dental prostheses fabricated using
      different computer-aided design/computer-aided manufacturing systems.
AB  - Besides load-bearing capacity, marginal accuracy is a further crucial factor
      influencing the clinical long-term reliability of fixed dental prostheses (FDPs).
      The aim of this in vitro study was to evaluate the marginal fit of four-unit
      zirconia bridge frameworks fabricated using four different computer-aided design
      (CAD)/computer-aided manufacturing (CAM) systems. Ten frameworks were
      manufactured using each fabricating system. Three systems (inLab, Everest,
      Cercon) processed white-stage zirconia blanks, which had to be sintered to final
      density after milling, while with one system (Digident) restorations were
      directly milled from a fully sintered material. After manufacturing, horizontal
      and vertical marginal discrepancies, as well as the absolute marginal
      discrepancy, were determined by means of a replica technique. The absolute
      marginal discrepancy, which is considered to be the most suitable parameter
      reflecting restorations' misfit in the marginal area, had a mean value of 58 mum
      for the Digident system. By contrast, mean absolute marginal discrepancies for
      the three other systems, processing presintered blanks, differed significantly
      and ranged between 183 and 206 mum. Within the limitations of this study, it
      could be concluded that the marginal fit of zirconia FDPs is significantly
      dependent on the CAD/CAM system used, with restorations processed of fully
      sintered zirconia showing better fitting accuracy.

PMID- 19583763
TI  - Morphological and bond strength evaluation of different resin cements to root
      dentin.
AB  - This study correlated the morphological characteristics with the bond strengths
      of various resin cements used for bonding fiber posts to root canal dentin. Fifty
      glass-fiber posts (FRC Postec Plus) were luted into the root canals of extracted
      human anterior teeth using five resin cements (n = 10): Panavia F 2.0, PermaFlo
      DC, Variolink II, RelyX Unicem, and Clearfil Core. Before insertion of the post,
      the adhesive systems were labeled with fluorescein and the resin cement was
      labeled with rhodamine isothiocyanate. The roots were sectioned into three slices
      (of 2 mm thickness), and each slice was analyzed using confocal laser scanning
      microscopy in dual fluorescence mode to determine hybrid layer thickness, the
      number of resin tags, and the number of broken tags. Bond strengths were measured
      using a micro push-out test. Bond strengths to root canal dentin, as well as the
      morphological characteristics, were significantly affected by the materials.
      However, these factors did not correlate. The self-adhesive resin cement, which
      showed the formation of a hybrid layer and resin tags only sporadically, had the
      highest bond strengths. These results indicate that chemical interactions between
      the adhesive cement and hydroxyapatite may be more crucial for root dentin
      bonding than the ability of the same material to hybridize dentin.

PMID- 19583764
TI  - Fluid flow after resin-composite restoration in extracted carious teeth.
AB  - The aim of this study was to investigate fluid flow in dentin after restoration
      of carious teeth with resin composite bonded with a total-etching adhesive, with
      or without glass-ionomer cement lining. The roots of extracted third molars were
      removed and the crowns were connected to a fluid flow-measuring device. Each
      carious lesion was stained with caries detector dye and caries was removed using
      slow-speed burs and spoon excavators. Caries-excavated teeth were divided into
      two groups for restoration with resin composite bonded with a total-etch
      adhesive: (i) without lining; and (ii) lined with glass-ionomer cement before
      bonding. In non-carious teeth, cavities of similar dimensions were prepared,
      divided into two groups, and restored in the same manner. Fluid flow was
      recorded, after restoration, for up to 1 month. Caries-affected dentin was
      examined by scanning electron microscopy (SEM), and the bonded interfaces were
      observed using a confocal laser scanning microscope. No significant difference in
      fluid flow was observed between the two restorative procedures or between the
      carious and non-carious groups. The SEM images showed that the dentinal tubules
      of acid-etched, caries-affected dentin were usually still occluded, while some
      were patent. Limited penetration of fluorescent dye into dentin and into the
      bonded interfaces of restored carious teeth was observed.

PMID- 19583765
TI  - Structural and mechanistic aspects of flavoproteins: photosynthetic electron
      transfer from photosystem I to NADP+.
AB  - This minireview covers the research carried out in recent years into different
      aspects of the function of the flavoproteins involved in cyanobacterial
      photosynthetic electron transfer from photosystem I to NADP(+), flavodoxin and
      ferredoxin-NADP(+) reductase. Interactions that stabilize protein-flavin
      complexes and tailor the midpoint potentials in these proteins, as well as many
      details of the binding and electron transfer to protein and ligand partners, have
      been revealed. In addition to their role in photosynthesis, flavodoxin and
      ferredoxin-NADP(+) reductase are ubiquitous flavoenzymes that deliver NAD(P)H or
      low midpoint potential one-electron donors to redox-based metabolisms in
      plastids, mitochondria and bacteria. They are also the basic prototypes for a
      large family of diflavin electron transferases with common functional and
      structural properties. Understanding their mechanisms should enable greater
      comprehension of the many physiological roles played by flavodoxin and ferredoxin
      NADP(+) reductase, either free or as modules in multidomain proteins. Many
      aspects of their biochemistry have been extensively characterized using a
      combination of site-directed mutagenesis, steady-state and transient kinetics,
      spectroscopy and X-ray crystallography. Despite these considerable advances,
      various key features of the structural-function relationship are yet to be
      explained in molecular terms. Better knowledge of these systems and their
      particular properties may allow us to envisage several interesting applications
      of these proteins beyond their physiological functions.

PMID- 19583766
TI  - Structural and mechanistic aspects of flavoproteins: probes of hydrogen
      tunnelling.
AB  - At least half of all enzyme-catalysed reactions are thought to involve a hydrogen
      transfer. In the last 10 years, it has become apparent that many of these
      reactions will occur, in part, or in full, by quantum mechanical tunnelling. We
      are particularly interested in the role of promoting vibrations on H transfer,
      and the Old Yellow Enzyme family of flavoproteins has proven to be an excellent
      model system with which to examine such reactions. In this minireview, we
      describe new and established experimental methods used to study H-tunnelling in
      these enzymes and we consider some practical issues important to such studies.
      The application of these methods has provided strong evidence linking protein
      dynamics and H-tunnelling in biological systems.

PMID- 19583768
TI  - Structural and mechanistic aspects of flavoproteins.

PMID- 19583769
TI  - Structural effects of a dimer interface mutation on catalytic activity of
      triosephosphate isomerase. The role of conserved residues and complementary
      mutations.
AB  - The active site of triosephosphate isomerase (TIM, EC: 5.3.1.1), a dimeric
      enzyme, lies very close to the subunit interface. Attempts to engineer monomeric
      enzymes have yielded well-folded proteins with dramatically reduced activity. The
      role of dimer interface residues in the stability and activity of the Plasmodium
      falciparum enzyme, PfTIM, has been probed by analysis of mutational effects at
      residue 74. The PfTIM triple mutant W11F/W168F/Y74W (Y74W*) has been shown to
      dissociate at low protein concentrations, and exhibits considerably reduced
      stability in the presence of denaturants, urea and guanidinium chloride. The
      Y74W* mutant exhibits concentration-dependent activity, with an approximately 22
      fold enhancement of k(cat) over a concentration range of 2.5-40 microM,
      suggesting that dimerization is obligatory for enzyme activity. The Y74W* mutant
      shows an approximately 20-fold reduction in activity compared to the control
      enzyme (PfTIM WT*, W11F/W168F). Careful inspection of the available crystal
      structures of the enzyme, together with 412 unique protein sequences, revealed
      the importance of conserved residues in the vicinity of the active site that
      serve to position the functional K12 residue. The network of key interactions
      spans the interacting subunits. The Y74W* mutation can perturb orientations of
      the active site residues, due to steric clashes with proximal aromatic residues
      in PfTIM. The available crystal structures of the enzyme from Giardia lamblia,
      which contains a Trp residue at the structurally equivalent position, establishes
      the need for complementary mutations and maintenance of weak interactions in
      order to accommodate the bulky side chain and preserve active site integrity.

PMID- 19583770
TI  - Biosynthesis of riboflavin. Screening for an improved GTP cyclohydrolase II
      mutant.
AB  - GTP cyclohydrolase II catalyzes the first dedicated step in the biosynthesis of
      riboflavin and appears to be a limiting factor for the production of the vitamin
      by recombinant Bacillus subtilis overproducer strains. Using error-prone PCR
      amplification, we generated a library of the B. subtilis ribA gene selectively
      mutated in the GTP cyclohydrolase II domain. The ratio of the GTP cyclohydrolase
      II to 3,4-dihydroxy-2-butanone synthase activities of the mutant proteins was
      measured. A mutant designated Construct E, carrying seven point mutations, showed
      a two-fold increase in GTP cyclohydrolase II activity and a four-fold increase in
      the K(m) value with GTP as the substrate. Using the analog 2-amino-5-formylamino
      6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate as the substrate, the mutant
      showed a rate enhancement by a factor of about two and an increase in the K(m)
      value by a factor of about 5. A series of UV absorption spectra obtained in
      stopped-flow experiments using the wild-type and mutant enzymes revealed
      isosbestic points indicative of apparently perfect reactions, which were similar
      to the findings obtained with GTP cyclohydrolase II of Escherichia coli. Initial
      burst velocities obtained for the mutant and wild-type proteins were similar. The
      data suggest that the mutations present in Construct E are jointly conducive to
      the acceleration of a late step in the reaction trajectory, most probably the
      release of product from the enzyme.

PMID- 19583767
TI  - Structural and mechanistic aspects of flavoproteins: electron transfer through
      the nitric oxide synthase flavoprotein domain.
AB  - Nitric oxide synthases belong to a family of dual-flavin enzymes that transfer
      electrons from NAD(P)H to a variety of heme protein acceptors. During catalysis,
      their FMN subdomain plays a central role by acting as both an electron acceptor
      (receiving electrons from FAD) and an electron donor, and is thought to undergo
      large conformational movements and engage in two distinct protein-protein
      interactions in the process. This minireview summarizes what we know about the
      many factors regulating nitric oxide synthase flavoprotein domain function,
      primarily from the viewpoint of how they impact electron input/output and
      conformational behaviors of the FMN subdomain.

PMID- 19583771
TI  - SAF-3, a novel splice variant of the SAF-1/MAZ/Pur-1 family, is expressed during
      inflammation.
AB  - The Cys2His2-type zinc finger transcription factor serum amyloid A activating
      factor 1 [SAF-1, also known as MAZ (myc-associated zinc finger protein) or Pur-1
      (purine binding factor-1)] plays an important role in regulation of a variety of
      inflammation-responsive genes. An SAF-2 splice variant acting as a negative
      regulator of SAF-1 was identified previously, and the present study reports the
      identification of a novel SAF-3 splice variant that is expressed during
      inflammation. SAF-3 mRNA, isolated from a cDNA library produced from IL-1beta
      induced cells, originates from a previously unknown first coding exon, and
      thereby contains a unique N-terminal domain but shares the same six zinc finger
      DNA-binding domains as present in SAF-1. In addition, a negatively functioning
      domain present at the N-terminus of SAF-1 and SAF-2 is spliced out in SAF-3. The
      expression of SAF-3 is very low in normal tissues and in cells grown under normal
      conditions. However, RT-PCR analysis of mRNAs from cytokine and growth factor
      induced cells as well of mRNAs isolated from several diseased tissues revealed
      abundant expression of SAF-3. The transactivation potential of SAF-3 is much
      greater than that of the predominantly expressed splice variant SAF-1. These
      findings show that transcriptional regulation of downstream inflammation
      responsive genes by SAF/MAZ/Pur-1 is likely to be more complex than previously
      assumed. In addition, we show that SAF-3 expression initiates from an upstream
      novel promoter. This is the first report of the existence of multiple promoters
      regulating expression of the SAF/MAZ/Pur-1 family of proteins.

PMID- 19583772
TI  - A novel antifungal hevein-type peptide from Triticum kiharae seeds with a unique
      10-cysteine motif.
AB  - Two forms of a novel antimicrobial peptide (AMP), named WAMP-1a and WAMP-1b, that
      differ by a single C-terminal amino acid residue and belong to a new structural
      type of plant AMP were purified from seeds of Triticum kiharae Dorof. et Migusch.
      Although WAMP-1a and WAMP-1b share similarity with hevein-type peptides, they
      possess 10 cysteine residues arranged in a unique cysteine motif which is
      distinct from those described previously for plant AMPs, but is characteristic of
      the chitin-binding domains of cereal class I chitinases. An unusual substitution
      of a serine for a glycine residue in the chitin-binding domain was detected for
      the first time in hevein-like polypeptides. Recombinant WAMP-1a was successfully
      produced in Escherichia coli. This is the first case of high-yield production of
      a cysteine-rich plant AMP from a synthetic gene. Assays of recombinant WAMP-1a
      activity showed that the peptide possessed high broad-spectrum inhibitory
      activity against diverse chitin-containing and chitin-free pathogens, with IC(50)
      values in the micromolar range. The discovery of a new type of AMP active against
      structurally dissimilar microorganisms implies divergent modes of action and
      discloses the complexity of plant-microbe interactions.

PMID- 19583773
TI  - Subcellular compartmentalization of FADD as a new level of regulation in death
      receptor signaling.
AB  - Fas-associated protein with death domain (FADD) is an essential adaptor protein
      in death receptor-mediated signal transduction. During apoptotic signaling, FADD
      functions in the cytoplasm, where it couples activated receptors with initiator
      caspase-8. However, in resting cells, FADD is predominantly stored in the
      nucleus. In this study, we examined the modalities of FADD intracellular
      trafficking. We demonstrate that, upon CD95 activation, FADD redistributes from
      the nucleus to the cytoplasm. This inducible nuclear-cytoplasmic translocation of
      FADD is independent of CD95 internalization, formation of the death-inducing
      signaling complex, and caspase-8 activation. In contrast to nuclear export of
      FADD, its subsequent recruitment and accumulation at endosomes containing
      internalized CD95 requires a caspase-8-dependent feedback loop. These data
      indicate the existence of differential pathways directing FADD nuclear export and
      cytoplasmic trafficking, and identify subcellular compartmentalization of FADD as
      a novel regulatory mechanism in death receptor signaling.

PMID- 19583774
TI  - NMR study of complexes between low molecular mass inhibitors and the West Nile
      virus NS2B-NS3 protease.
AB  - The two-component NS2B-NS3 protease of West Nile virus is essential for its
      replication and presents an attractive target for drug development. Here, we
      describe protocols for the high-yield expression of stable isotope-labelled
      samples in vivo and in vitro. We also describe the use of NMR spectroscopy to
      determine the binding mode of new low molecular mass inhibitors of the West Nile
      virus NS2B-NS3 protease which were discovered using high-throughput in vitro
      screening. Binding to the substrate-binding sites S1 and S3 is confirmed by
      intermolecular NOEs and comparison with the binding mode of a previously
      identified low molecular mass inhibitor. Our results show that all these
      inhibitors act by occupying the substrate-binding site of the protease rather
      than by an allosteric mechanism. In addition, the NS2B polypeptide chain was
      found to be positioned near the substrate-binding site, as observed previously in
      crystal structures of the protease in complex with peptide inhibitors or bovine
      pancreatic trypsin inhibitor. This indicates that the new low molecular mass
      compounds, although inhibiting the protease, also promote the proteolytically
      active conformation of NS2B, which is very different from the crystal structure
      of the protein without inhibitor.

PMID- 19583775
TI  - Tyrosine nitration in the human leucocyte antigen-G-binding domain of the Ig-like
      transcript 2 protein.
AB  - Ig-like transcript 2 (ILT2) is a suppressive receptor that participates in the
      control of the autoimmune reactivity. This action is usually carried out in a
      proinflammatory microenvironment where there is a high production of free
      radicals and NO. However, little is known regarding whether these conditions
      modify the protein or affect its suppressive functions. The present study aimed
      to investigate the suppressive response of the ILT2 receptor under oxidative
      stress. To address this topic, we treated the ILT2-expressing natural killer cell
      line, NKL, with the NO donor N-(4-[1-(3-aminopropyl)-2-hydroxy-2
      nitrosohydrazino]butyl)propane-1,3-diamine (DETA-NO). We observed that DETA-NO
      caused ILT2 protein nitration. MS analysis of the chimeric recombinant human ILT2
      Fc protein after treatment with the peroxynitrite donor 3-(morpholinosydnonimine
      hydrochloride) (SIN-1) showed the nitration of Tyr35, Tyr76 and Tyr99, which are
      involved in human leucocyte antigen-G binding. This modification is selective
      because other Tyr residues were not modified by SIN-1. Recombinant human ILT2-Fc
      treated with SIN-1 bound a significantly higher quantity of human leucocyte
      antigen-G than untreated recombinant human ILT2-Fc. DETA-NO did not modify ILT2
      mRNA expression or protein expression at the cell surface. Preincubation of NKL
      cells with DETA-NO decreased the cytotoxic lysis of K562-human leucocyte antigen
      G1 cells compared to untreated NKL cells (P < 0.05) but increased cytotoxicity
      against K562-pcDNA cells (P < 0.05). Intracellular tyrosine phosphorylation
      produced after human leucocyte antigen-G binding was not affected by DETA-NO cell
      pretreatment. These results support the hypothesis that the ILT2human leucocyte
      antigen-G interaction should have a central role in tolerance under oxidative
      stress conditions when other tolerogenic mechanisms are inhibited.

PMID- 19583776
TI  - Structure of the HIV-1 Rev response element alone and in complex with regulator
      of virion (Rev) studied by atomic force microscopy.
AB  - The interaction of multiple HIV-1 regulator of virion (Rev) proteins with the
      viral RNA target, the Rev response element (RRE), is critical for nuclear export
      of incompletely spliced and unspliced viral RNA, and for the onset of the late
      phase in the viral replication cycle. The heterogeneity of the Rev-RRE complex
      has made it difficult to study using conventional structural methods. In the
      present study, atomic force microscopy is applied to directly visualize the
      tertiary structure of the RRE RNA alone and in complex with Rev proteins. The
      appearance of the RRE is compatible with the earlier proposed RRE secondary
      structure in dimensions and overall shape, including a stalk and a head
      interpreted as stem I, and stem-loops II-V in the secondary structure model,
      respectively. Atomic force microscopy imaging of the Rev-RRE complex revealed an
      increased height of the structure both in the stalk and head regions, which is in
      accordance with a binding model in which Rev binding to a high affinity site in
      stem IIB triggers oligomerization of Rev proteins through cooperative binding
      along stem I in RRE. The present study demonstrates that atomic force microscopy
      comprises a useful technique to study complex biological structures of nucleic
      acids at high resolution.

PMID- 19583777
TI  - The transcription factor ZBP-89 suppresses p16 expression through a histone
      modification mechanism to affect cell senescence.
AB  - The transcription factor ZBP-89 has been implicated in the induction of growth
      arrest and apoptosis. In this article, we demonstrate that ZBP-89 was able to
      restrain senescence in NCI-H460 human lung cancer cells, through epigenetically
      regulating p(16INK4a) expression. Specifically, our results indicate that
      knockdown of ZBP-89 by RNA interference stimulated cellular senescence in NCI
      H460 cells, as judged by the senescence-associated beta-galactosidase activity
      assay and senescence-associated heterochromatin foci assay, and this process
      could be reversed by RNA interference-mediated p16(INK4a) silencing. We also show
      that histone deacetylase (HDAC) 3 and HDAC4 inhibited p16(INK4a) promoter
      activity in a dose-dependent manner. Furthermore, chromatin immunoprecipitation
      assays verified that HDAC3 was recruited to the p16(INK4a) promoter by ZBP-89
      through an epigenetic mechanism involving histone acetylation modification.
      Moreover, immunofluorescence and coimmunoprecipitation assays revealed that ZBP
      89 and HDAC3 formed a complex. These data suggest that ZBP-89 and HDAC3, but not
      HDAC4, can work coordinately to restrain cell senescence by downregulating
      p16(INK4a) expression through an epigenetic modification of histones.

PMID- 19583778
TI  - Seric and secretory antibodies reactive to alpha, beta and gamma intimins of
      Escherichia coli in healthy Brazilian adults.
AB  - Intimin is essential for attaching and effacing lesions by pathogens such as
      enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC),
      and the antigenic polymorphism of intimin determines distinct subtypes. Our aim
      was to investigate the presence of immunoglobulin G (IgG) and IgA antibodies
      reactive to alpha, beta and gamma intimins in serum and colostrum from healthy
      Brazilian adults. We found seric IgG and secretory IgA antibodies reactive to
      conserved and variable regions of alpha, beta and gamma intimins and a positive
      correlation between the concentrations of these antibodies in both serum and
      colostrum that suggested cross reactivity among anti-intimin antibodies, as was
      confirmed by immunoblotting and absorption. The concentrations of anti-conserved
      region antibodies were higher than those of variable region antibodies. The
      presence of antibodies reactive to EHEC antigens could result from contact with
      EPEC or with other bacteria of the environment even though this bacterium is not
      frequent in Brazil, and suggests possible protection against EHEC.

PMID- 19583779
TI  - Patients with epilepsy: cognitively compromised before the start of antiepileptic
      drug treatment?
AB  - PURPOSE: To compare the cognitive profile of newly diagnosed untreated epilepsy
      patients with healthy volunteers using a comprehensive neuropsychological test
      battery. METHODS: A total of 155 untreated patients with newly diagnosed
      epilepsy, and no known brain pathology, were assessed before the start of
      treatment with antiepileptic medication. Their scores across the
      neuropsychological measures were compared with 87 healthy volunteers from the
      general population equated for age and sex. RESULTS: After adjusting for age,
      sex, and education, patients with epilepsy performed significantly worse than
      healthy volunteers on 6 of 14 cognitive measures, particularly in the domains of
      memory and psychomotor speed. Cognitive performance was not related to the number
      of seizures, type of epilepsy, or mood. When an impairment index was calculated,
      53.5% patients had a least one abnormal score [>2 standard deviations (SD) below
      the control mean] on the test battery compared with 20.7% of healthy volunteers.
      DISCUSSION: Newly diagnosed untreated patients with epilepsy are cognitively
      compromised before the start of antiepileptic drug medication. The domains most
      affected are memory and psychomotor speed. More than one-half of the patients had
      at least one abnormal test score across the test battery. There were no
      differences in epilepsy-related or mood variables between those who demonstrated
      dysfunction and those that did not.

PMID- 19583780
TI  - Doublecortin expression in focal cortical dysplasia in epilepsy.
AB  - PURPOSE: Doublecortin (DCX) is a microtubule-associated protein with regulatory
      roles in radial and tangential migration of neurons during cortical development.
      In normal adult cortex there is restricted expression, and DCX is widely used as
      a marker of neurogenesis. Imperfect corticogenesis is thought to underpin many
      focal cortical pathologies in epilepsy surgical series, including focal cortical
      dysplasia (FCD). The aim was to study DCX expression patterns in such lesions
      compared to normal developing and mature cortex. METHOD: Cases of FCD types Ia
      (13) and IIb (4), pediatric hippocampal sclerosis (HS) (5), temporal lobe
      sclerosis (5), glioneuronal tumors (5), gray matter heterotopia (3), and control
      tissues (16) from a wide age range [20 gestational weeks (GW) to 85 years] were
      studied using immunohistochemistry to DCX. RESULTS: In controls and all epilepsy
      cases, perinuclear labeling of small round cells (SRCs) and satellite
      perineuronal cells was observed in both postmortem and surgical tissues. In FCD
      Ia up to the age of 4 years, prominent DCX-positive (DCX(+)), immature cells were
      present along the junction of layers I and II, with processes extending into the
      molecular layer. These cell types were not a significant feature in other
      pathologies, which showed multipolar DCX(+) cells or labeling of dysmorphic cells
      throughout the cortex. DISCUSSION: Persistent cellular DCX expression is
      confirmed in normal adult cortex. Characteristic expression patterns in layer II
      of FCD Ia could indicate delayed or abnormal cortical maturation rather than
      ongoing cytogenesis. This could be indicative of enhanced local cortical
      plasticity as well as a potential diagnostic feature of this type of pathology.

PMID- 19583781
TI  - Doublecortin-like (DCL) expression in focal cortical dysplasia and cortical
      tubers.
AB  - PURPOSE: Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of
      patients with tuberous sclerosis complex (TSC) are malformations of cortical
      development that are frequently associated with intractable epilepsy. Their
      histopathologic and molecular features suggest developmental abnormalities during
      the early stages of cortical development, which may involve neural progenitor
      cells. The aim of our study was to define the expression and cell-specific
      distribution of doublecortin-like (DCL), a protein critically involved in
      neuronal division and radial migration during early corticogenesis, in both FCD
      and TSC. METHODS: DCL was studied in epilepsy surgery cases with FCD IIB (n = 8)
      and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis,
      and Western blotting. RESULTS: Autopsy and surgical control neocortical specimens
      were characterized by modest DCL immunoreactivity (IR) throughout all cortical
      layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in
      FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large
      dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression
      of DCL with the neural progenitor or neuroblast markers nestin, GFAPdelta, and
      doublecortin was observed in both FCD and TSC specimens. The increased DCL
      expression within the dysplastic cortex, compared to control cortex, was
      confirmed by Western blot analysis. DISCUSSION: The prominent postnatal
      expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role
      for this microtubule associated protein, also during early human cortical
      development, which could be relevant to the pathogenesis of these developmental
      glioneuronal malformations.

PMID- 19583782
TI  - Economic burden of epilepsy in a developing country: a retrospective cost
      analysis in China.
AB  - PURPOSE: To study the cost of epilepsy in China, and, therefore, provide
      essential information on the burden of the disease to individuals and society.
      METHODS: A cost-of-illness study was performed on a retrospective cohort of
      medically treated patients. Data on clinical characteristics, utilization of
      sources, and costs were collected from 289 patients in a standardized format.
      RESULTS: Direct medical care costs was Chinese yuan, renminbi (RMB) 2,529 (USD
      372) per year per patient, of which antiepileptic drugs (RMB 1,651 or USD 243)
      accounted for the major cost component. Nonmedical direct costs were much less
      than direct health care costs, averaging approximately RMB 756 (USD 111). Costs
      due to loss of productivity averaged approximately RMB 1,968 (USD 289) per
      patient per year. Taken together, the overall mean annual cost for epilepsy per
      patient in our series was approximately RMB 5,253 (USD 773), and these costs
      accounted for more than half of the mean annual income. Total cost was
      significantly associated with disease severity and different responses to drug
      treatment. In addition, new antiepileptic drugs and the number of drugs taken
      were closely related with the drug cost. CONCLUSION: The results indicate that
      the economic burden of epilepsy to both Chinese patients and the nation is heavy,
      and the composition proportions of the costs in China have many similar features
      and some noteworthy differences with that of other countries.

PMID- 19583783
TI  - Prevalence, incidence, and clinical characteristics of epilepsy--a community
      based door-to-door study in northern Tanzania.
AB  - PURPOSE: The main aim of this door-to-door-study was to determine the prevalence,
      incidence, and clinical characteristics of epilepsy in northern Tanzania.
      METHODS: A total of 7,399 people were screened with a standardized questionnaire
      using "multistage random sampling." RESULTS: The prevalence rate of epilepsy was
      11.2/1,000 [95% confidence interval (CI) 8.9-13.9/1,000] and the age-adjusted
      prevalence rate was 13.2/1,000. The prevalence of active epilepsy was 8.7/1,000
      (95% CI 6.7-11/1,000). There was a preponderance of women. The average
      retrospective incidence including the last 5 years was 81.1/100,000 (95% CI 65
      101/100,000). Fifty-four percent (45 of 83) of the people with epilepsy had
      generalized seizures without any identifiable cause; 71% (59 of 83) of the
      epilepsy patients had not visited health institutions prior to the study and 76%
      (63 of 83) had never received treatment. DISCUSSION: Our study shows that the
      prevalence and incidence of epilepsy in northern Tanzania are higher compared to
      developed countries and that the majority of people with epilepsy do not access
      treatment.

PMID- 19583784
TI  - Ring chromosome 20 syndrome: a link between epilepsy onset and neuropsychological
      impairment in three children.
AB  - PURPOSE: Ring chromosome 20 [r(20)] syndrome is a well-defined chromosomal
      disorder characterized by epilepsy, mild-to-moderate mental retardation, and lack
      of recognizable dysmorphic features. Epilepsy is often the most important
      clinical manifestation of the syndrome, even if its appearance is not constantly
      precocious. Seizures are frequently drug resistant. METHODS: We describe three
      children with [r(20)] syndrome in whom the onset of epilepsy (age at onset range:
      4 years and 6 months to 9 years and 4 months) determined a kind of epileptic
      status (age at onset range: 6 years and 10 months to 9 years and 8 months) with
      dramatic neuropsychological deterioration. This epileptic status lasted for
      several months because of refractoriness to most antiepileptic drugs (AEDs), but
      it was treated successfully with a combination of valproate and lamotrigine in
      two children. RESULTS: As soon as seizures stopped, the children showed prompt
      recovery with partial restoration of the neuropsychological impairment.
      CONCLUSION: This clinical picture can be described as abrupt epileptic
      encephalopathy.

PMID- 19583785
TI  - Molecular characterization of bacteria associated with the trophosome and the
      tube of Lamellibrachia sp., a siboglinid annelid from cold seeps in the eastern
      Mediterranean.
AB  - Specimens of Lamellibrachia (Annelida: Siboglinidae) were recently discovered at
      cold seeps in the eastern Mediterranean. In this study, we have investigated the
      phylogeny and function of intracellular bacterial symbionts inhabiting the
      trophosome of specimens of Lamellibrachia sp. from the Amon mud volcano, as well
      as the bacterial assemblages associated with their tube. The dominant
      intracellular symbiont of Lamellibrachia sp. is a gammaproteobacterium closely
      related to other sulfide-oxidizing tubeworm symbionts. In vivo uptake experiments
      show that the tubeworm relies on sulfide for its metabolism, and does not utilize
      methane. Bacterial communities associated with the tube form biofilms and occur
      from the anterior to the posterior end of the tube. The diversity of 16S rRNA
      gene phylotypes includes representatives from the same divisions previously
      identified from the tube of the vent species Riftia pachyptila, and others
      commonly found at seeps and vents.

PMID- 19583786
TI  - Rumen protozoa are rich in polyunsaturated fatty acids due to the ingestion of
      chloroplasts.
AB  - Within this study, we investigated whether the polyunsaturated fatty acids (PUFA)
      rich nature of rumen protozoa is a consequence of ingestion of PUFA-rich
      chloroplasts. Four Hereford x Friesian steers were offered hay [low 18:3 (n-3)
      and low chlorophyll concentration] followed by freshly cut perennial ryegrass
      [high 18:3 (n-3) and high chlorophyll concentration] for 16 days. On the 14th and
      16th days, rumen protozoa as well as attached and planktonic bacteria were
      fractionated 1 h before (-1 h), 2 and 6 h postfeeding, and their fatty acid
      concentrations determined. Protozoa fractionated from fresh grass-fed steers were
      richer (P<0.05) in PUFA, except conjugated linoleic acid, for all time points
      compared with those from hay-fed steers. Protozoal density was higher (P<0.05)
      for grass compared with hay. Entodinomorphid abundance was 3.4 times higher on
      fresh grass (P<0.01) compared with hay. Confocal microscopy and transmission
      electron microscopy confirmed that Epidinium spp. were commonly saturated with
      intracellular cytoplasmic chloroplasts. These data suggest that engulfment of
      chloroplasts is a major contributor to the high 18:3 (n-3) concentration of
      protozoa.

PMID- 19583787
TI  - Localization and transmission route of Coriobacterium glomerans, the endosymbiont
      of pyrrhocorid bugs.
AB  - Endosymbiotic gut bacteria play an essential role in the nutrition of many
      insects. Most of the nutritional interactions investigated so far involve
      gammaproteobacterial symbionts, whereas other groups have received comparatively
      little attention. Here, we report on the localization and the transmission route
      of the specific actinobacterial symbiont Coriobacterium glomerans from the gut of
      the red firebug, Pyrrhocoris apterus (Hemiptera: Pyrrhocoridae). The symbionts
      were detected by diagnostic PCRs and FISH in the midgut section M3, in the rectum
      and in feces of the bugs as well as in the hemolymph of some females.
      Furthermore, adult female bugs apply the symbionts to the surface of the eggs
      during oviposition, from where they are later taken up by the hatchlings. Surface
      sterilization of egg clutches generated aposymbiotic insects and thereby
      confirmed the vertical transmission route via the egg surface. However, symbionts
      were readily acquired horizontally when the nymphs were reared in the presence of
      symbiont-containing eggshells, feces, or adult bugs. Using diagnostic PCRs and
      partial sequencing of the 16S rRNA gene, closely related bacterial symbionts were
      detected in the cotton stainer bug Dysdercus fasciatus (Hemiptera:
      Pyrrhocoridae), suggesting that the symbiosis with Actinobacteria may be
      widespread among pyrrhocorid bugs.

PMID- 19583788
TI  - Archaea in the Gulf of Aqaba.
AB  - Using a polyphasic approach, we examined the presence of Archaea in the Gulf of
      Aqaba, a warm marine ecosystem, isolated from major ocean currents and subject to
      pronounced seasonal changes in hydrography. Catalyzed reported deposition FISH
      analyses showed that Archaea make up to >20% of the prokaryotic community in the
      Gulf. A spatial separation between the two major phyla of Archaea was observed
      during summer stratification. Euryarchaeota were found exclusively in the upper
      200 m, whereas Crenarchaeota were present in greater numbers in layers below the
      summer thermocline. 16S rRNA gene-based denaturing gradient gel electrophoresis
      confirmed this depth partitioning and revealed further diversity of Crenarchaeota
      and Euryarchaeota populations along depth profiles. Phylogenetic analysis showed
      pelagic Crenarchaeota and Euryarchaeota to differ from coral-associated Archaea
      from the Gulf, forming distinct clusters within the Marine Archaea Groups I and
      II. Endsequencing of fosmid libraries of environmental DNA provided a tentative
      identification of some members of the archaeal community and their role in the
      microbial community of the Gulf. Incorporation studies of radiolabeled leucine
      and bicarbonate in the presence of different inhibitors suggest that the archaeal
      community participates in autotrophic CO(2) uptake and contributes little to the
      heterotrophic activity.

PMID- 19583790
TI  - A novel circuit overrides Adr1p control during expression of Saccharomyces
      cerevisiae 2-trans-enoyl-ACP reductase Etr1p of mitochondrial type 2 fatty acid
      synthase.
AB  - The significance of the chronicled role of the yeast transcription factor Adr1p
      in regulating ETR1 was examined in wild type and isogenic adr1Delta mutant cells.
      An ETR1-lacZ reporter construct was used to verify Adr1p-dependent gene
      expression. On solid glycerol medium containing X-gal, wild-type cells expressing
      the reporter turned blue, whereas the adr1Delta mutants remained white. beta
      Galactosidase activity measurements following 24-h cell growth in liquid glycerol
      medium revealed a 6.5-fold greater expression level of the reporter gene in the
      wild type compared with the adr1Delta mutant. In contrast, immunoblotting showed
      that Etr1p abundance was essentially indistinguishable between the two strains
      whereas Cta1p, whose expression depends on Adr1p, was present in the wild-type
      cells, but not in the mutants. Moreover, enzyme assays conducted on transformed
      wild-type and adr1Delta mutant cells expressing a plasmid-borne ETR1 tethered
      behind the native promoter revealed similar levels of reductase activity, and the
      lipoic acid content in the two parental strains was equivalent. Hence, while
      Adr1p influenced the transcription levels of ETR1, it did not alter the abundance
      of Etr1p, the level of reductase activity, or the cellular amount of lipoic acid.
      The results point toward a potentially novel layer of control for maintaining
      physiological levels of lipoic acid.

PMID- 19583789
TI  - Subseafloor microbial communities associated with rapid turbidite deposition in
      the Gulf of Mexico continental slope (IODP Expedition 308).
AB  - The subseafloor microbial communities in the turbidite depositional basins Brazos
      Trinity Basin IV (BT Basin) and the Mars-Ursa Basin (Ursa Basin) on the Gulf of
      Mexico continental slope (IODP holes U1319A, U1320A, U1322B and U1324B) were
      investigated by PCR-dependent molecular analyses targeted to the small subunit
      (SSU) rRNA genes, dsrA and mcrA, and hydrogenase activity measurements. Biomass
      at both basins was very low, with the maximum cell or the SSU rRNA gene copy
      number <1 x 10(7) cells mL(-1) or copies g(-1) sediments, respectively.
      Hydrogenase activity correlated with biomass estimated by SSU rRNA gene copy
      number when all data sets were combined. We detected differences in the SSU rRNA
      gene community structures and SSU rRNA gene copy numbers between the basin-fill
      and basement sediments in the BT Basin. Examination of microbial communities and
      hydrogenase activity in the context of geochemical and geophysical parameters and
      sediment depositional environments revealed that differences in microbial
      community composition between the basin-fill and basement sediments in the BT
      Basin were associated with sedimentation regimes tied to the sea-level change.
      This may also explain the distributions of relatively similar archaeal
      communities in the Ursa Basin sediments and basement sediments in the BT Basin.

PMID- 19583791
TI  - Genome-wide identification of novel genomic islands that contribute to Salmonella
      virulence in mouse systemic infection.
AB  - Salmonella pathogenicity islands are inserted into the genome by horizontal gene
      transfer and are required for expression of full virulence. Here, we performed
      tRNA scanning of the genome of Salmonella enterica serovar Typhimurium and
      compared it with that of nonpathogenic Escherichia coli in order to identify
      genomic islands that contribute to Salmonella virulence. Using deletion analysis,
      we identified four genomic islands that are required for virulence in the mouse
      infection model. One of the newly identified pathogenicity islands was the pheV
      tRNA-located genomic island, which is comprised of 26 126 bp, and encodes 22
      putative genes, including STM3117-STM3138. We also showed that the pheV tRNA
      located genomic island is widely distributed among different nontyphoid
      Salmonella serovars. Furthermore, genes including STM3118-STM3121 were identified
      as novel virulence-associated genes within the pheV-tRNA-located genomic island.
      These results indicate that a Salmonella-specific pheV-tRNA genomic island is
      involved in Salmonella pathogenesis among the nontyphoid Salmonella serovars.

PMID- 19583792
TI  - Aerobic methanol-oxidizing bacteria in soil.
AB  - Methanol is an atmospheric compound that is primarily released from plant
      polymers and impacts ozone formation. The global methanol emission rate from
      terrestrial ecosystems is of the same order of magnitude (4.9 x 10(12) mol year(
      1)) as that of methane (10 x 10(12) mol year(-1)). The major proportion of the
      annual plant-released methanol does not enter the atmosphere, but may be
      reoxidized by biological methanol oxidation, which is catalyzed by methanol
      oxidizing prokaryotes. Fifty-six aerobic methanol-oxidizing species have been
      isolated from soils. These methylotrophs belong to the Alpha-, Beta-, and
      Gammaproteobacteria, Verrucomicrobia, Firmicutes, and Actinobacteria. Their
      ecological niches are determined by oxygen and methanol concentration,
      temperature, pH, the capability to utilize nitrate as an electron acceptor, and
      the spectrum of nitrogen sources and utilizable multicarbon substrates. Recently
      discovered interactions with eukaryotes indicate that their ecological niches may
      not solely be defined by physicochemical parameters. Nonetheless, there are still
      gaps in knowledge; based on global methanol budgets, methanol oxidation in soil
      is important, but has not been addressed adequately by biogeochemical studies.
      Ratios of above-ground and soil-internal methanol oxidation are not known. The
      contribution to methanol-oxidation by aerobic and anaerobic methylotrophs in situ
      also needs further research.

PMID- 19583794
TI  - Development of a PCR assay for identification of the Bacillus cereus group
      species.
AB  - AIMS: A PCR technique was developed as a reliable and rapid identification method
      for the Bacillus cereus group species, based on a unique conserved sequence of
      the motB gene (encoding flagellar motor protein) from B. cereus, Bacillus
      thuringiensis and Bacillus anthracis. METHODS AND RESULTS: Primer locations were
      identified against eight strains of the B. cereus group spp. from nucleotide
      sequences available in the National Centre for Biotechnology Information
      database. The PCR assay was applied for the identification of 117 strains of the
      B. cereus group spp. and 19 strains from other microbial species, with special
      emphasis on foodborne pathogens. CONCLUSION: The designed cross-species primers
      are group specific and did not react with DNA from other Bacillus and non
      Bacillus species either motile or not. The primers system enabled us to detect
      10(3) CFU of B. cereus cells per millilitre of sample. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Bacillus cereus group spp. belongs to one of the most prevalent
      foodborne pathogens. Bacterial growth results in production of different toxins;
      therefore, consumption of food containing >10(6) bacteria per gram may result in
      emetic and diarrhoeal syndromes. A rapid and sensitive bacterial detection method
      is significant for food safety.

PMID- 19583793
TI  - Cloning and comparison of phylogenetically related chitinases from Listeria
      monocytogenes EGD and Enterococcus faecalis V583.
AB  - AIMS: To compare enzymatic activities of two related chitinases, ChiA and EF0361,
      encoded by Listeria monocytogenes and Enterococcus faecalis, respectively.
      METHODS AND RESULTS: The chiA and EF0361 genes were amplified by PCR, cloned and
      expressed with histidine tags, allowing easy purification of the gene products.
      ChiA had a molecular weight as predicted from the amino acid sequence, whereas
      EF0361 was 1840 Da lower than expected because of C-terminal truncation. The ChiA
      and EF0361 enzymes showed activity towards 4-nitrophenyl N,N'-diacetyl-beta-D
      chitobioside with K(m) values of 1.6 and 2.1 mmol l(-1), respectively, and k(cat)
      values of 21.6 and 6.5 s(-1). The enzymes also showed activity towards 4
      nitrophenyl beta-D-N, N', N''-triacetylchitotriose and carboxy-methyl-chitin
      Remazol Brilliant Violet but not towards 4-nitrophenyl N-acetyl-beta-D
      glucosaminide. Chitinolytic specificities of the enzymes were supported by their
      inactivity towards the substrates 4-nitrophenyl beta-D-cellobioside and
      peptidoglycan. The pH and temperature profiles for catalytic activities were
      relatively similar for both the enzymes. CONCLUSION: The ChiA and EF0361 enzymes
      show a high degree of similarity in their catalytic activities although their
      hosts share environmental preferences only to some extent. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study contributes to an understanding of the
      chitinolytic activities by L. monocytogenes and Ent. faecalis. Detailed
      information on their chitinolytic systems will help define potential reservoirs
      in the natural environment and possible transmission routes into food
      manufacturing plants.

PMID- 19583795
TI  - Mobility and survival of Salmonella Typhimurium and human adenovirus from spiked
      sewage sludge applied to soil columns.
AB  - AIMS: This study investigated the survival and transport of sewage sludge-borne
      pathogenic organisms in soils. METHODS AND RESULTS: Undisturbed soil cores were
      treated with Salmonella enterica ssp. enterica serovar Typhimurium-lux (STM-lux)
      and human adenovirus (HAdV)-spiked sewage sludge. Following an artificial
      rainfall event, these pathogens were analysed in the leachate and soil sampled
      from different depths (0-5 cm, 5-10 cm and 10-20 cm) after 24 h, 1 and 2 months.
      Significantly more STM-lux and HAdV leached through the soil cores when sewage
      sludge was present. Significantly more STM-lux were found at all soil depths, at
      all time periods in the sewage sludge treatments, compared to the controls. The
      rate of decline of STM-lux in the controls was more rapid than in the sewage
      sludge treatments. Survival and transport of HAdV were minimal. CONCLUSIONS: The
      presence of sewage sludge can significantly influence the transport and survival
      of bacterial pathogens in soils, probably because of the presence of organic
      matter. Environmental contamination by virus is unlikely because of strong soil
      adsorption. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that
      groundwater contamination from vertical movement of pathogens is a potential risk
      and that it highlights the importance of the treatment requirements for biosolids
      prior to their application to land.

PMID- 19583796
TI  - Two-stage fermentation process for alginate production by Azotobacter vinelandii
      mutant altered in poly-beta-hydroxybutyrate (PHB) synthesis.
AB  - AIMS: A two-stage fermentation strategy, based on batch cultures conducted first
      under non-oxygen-limited conditions, and later under oxygen-limited conditions,
      was used to improve alginate production by Azotobacter vinelandii (AT6), a strain
      impaired in poly-beta-hydroxybutyrate (PHB) production. METHODS AND RESULTS: The
      use of sucrose as carbon source, as well as a high oxygen concentration (10%),
      allowed to obtain a maximum biomass concentration of 7.5 g l(-1) in the first
      stage of cultivation. In the second stage, the cultures were limited by oxygen
      (oxygen close to 0%) and fed with a sucrose solution at high concentration. Under
      those conditions, the growth rate decreased considerably and the cells used the
      carbon source mainly for alginate biosynthesis, obtaining a maximum concentration
      of 9.5 g l(-1), after 50 h of cultivation. CONCLUSION: Alginate concentration
      obtained from the AT6 strain was two times higher than that obtained using the
      wild-type strain (ATCC 9046) and was the highest reported in the literature.
      However, the mean molecular mass of the alginate produced in the second stage of
      the process by the mutant AT6 was lower (400 kDa) than the polymer molecular mass
      obtained from the cultures developed with the parental strain (950 kDa).
      SIGNIFICANCE AND IMPACT OF THE STUDY: The use of a mutant of A. vinelandii
      impaired in the PHB production in combination with a two-stage fermentation
      process could be a feasible strategy for the production of alginate at industrial
      level.

PMID- 19583797
TI  - The role of aminopeptidase PepS in the growth of Streptococcus thermophilus is
      not restricted to nitrogen nutrition.
AB  - AIMS: To investigate the effect of an absence of aminopeptidase PepS on the
      growth of Streptococcus thermophilus on different media and at different
      temperatures. METHODS AND RESULTS: Using gene interruption, a negative mutant of
      the Strep. thermophilus CNRZ385 strain was constructed for the aminopeptidase
      PepS (strain DeltapepS). Checks were first of all made using biochemical assays
      that the DeltapepS strain lacks the peptide hydrolase activity of aminopeptidase
      PepS. It was demonstrated that the absence of the aminopeptidase PepS exerted a
      negative effect on growth whatever the culture medium (M17, chemically defined
      medium, milk). The role of aminopeptidase PepS in growth was enhanced at a high
      temperature (45 degrees C vs 37 degrees C). The DeltapepS strain was more
      resistant to lysozyme than the wild-type strain. CONCLUSIONS: We were able to
      demonstrate that aminopeptidase PepS probably plays a pleiotropic role through
      its involvement in growth via nitrogen nutrition, as well as via other cellular
      functions/metabolisms (such as peptidoglycane metabolism). SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study constitutes the first report on the role of a
      member of the M29 MEROPS family of metallopeptidases
      (http://merops.sanger.ac.uk/).

PMID- 19583798
TI  - Effect of starter culture inoculation on feed hygiene and microbial population
      development in fermented pig feed composed of a cereal grain mix with wet wheat
      distillers' grain.
AB  - AIMS: Investigating the influence of an added starter culture on the properties
      of fermented liquid pig feed. METHODS AND RESULTS: Diets of cereal grain blended
      with wet wheat distillers' grain that were either not inoculated (WWDG),
      inoculated with a silage starter culture at start (WWDGsc1) or at start and at
      each backslopping (replacement of 80% the content with fresh mixture, simulating
      feed outtake, WWDGsc5) were fermented for 5 days, followed by 5 days of daily
      backslopping. Numbers of undesirable micro-organisms (enterobacteria, moulds)
      were reduced in all fermentations; particularly enterobacteria in the starter
      culture inoculated diets. Lactobacillus plantarum present in the starter culture
      became dominant in diets WWDGsc1 and WWDGsc5. However, Lactobacillus panis that
      was dominating WWDG was also abundant in WWDGsc1 and WWDGsc5. Yeast populations
      were not influenced by the starter culture, with Pichia fermentans dominating all
      fermentations. All diets had similar chemical characteristics with the exception
      of a significant increase of all tested organic acids in WWDGsc5. CONCLUSIONS:
      The addition of a starter culture influences the bacterial population in
      fermented liquid feed, but there is also a strong impact of the flora already
      present in the feed ingredients. The yeast population is not influenced by adding
      a lactic acid bacteria (LAB) starter culture. A consortium of LAB and yeast
      strains adapted to the fermentation should be used as starter culture.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that it is possible to
      influence the current unpredictable and spontaneous process of feed fermentation
      when appropriate starter cultures are used. For this purpose, LAB and yeasts with
      desirable characteristics should be isolated.

PMID- 19583799
TI  - Antimicrobial mortar surfaces for the improvement of hygienic conditions.
AB  - AIMS: To evaluate the effectiveness of various antimicrobial mortar formulations
      in inhibiting the growth of a selection of pathogens of environmental and
      hygienic concern. METHODS AND RESULTS: Mortar prisms containing triclosan
      incorporated fibres or different concentrations of silver copper zeolites were
      incubated with Escherichia coli, Listeria monocytogenes, Salmonella enterica or
      Staphylococcus aureus at 4 or 20 degrees C for 24 h. From plate counting, a
      substantial bactericidal effect (>4 log units) could only be observed for the
      mortar specimens containing more than 3% zeolites on cement weight base, the
      effect being more pronounced at 20 degrees C compared to 4 degrees C. No
      inhibitory effect could be observed for mortar specimens containing antimicrobial
      fibres. Adenosinetriphosphate (ATP) measurements allowed for a rapid indication
      of the occurrence of antimicrobial activity. CONCLUSIONS: In order to obtain a
      bactericidal effect on mortar surfaces, concentrations of silver copper zeolites
      of more then 3% are required. SIGNIFICANCE AND IMPACT OF THE STUDY: To our
      knowledge, this is the first study in which the effectiveness of various
      antimicrobial mortar mixtures towards the inhibition of pathogens has been
      evaluated in a quantitative way. Antimicrobial concrete mixtures can be used for
      the improvement of the hygienic conditions in a variety of environments.

PMID- 19583800
TI  - Applicability of the 16S-23S rDNA internal spacer for PCR detection of the
      phytostimulatory PGPR inoculant Azospirillum lipoferum CRT1 in field soil.
AB  - AIMS: To assess the applicability of the 16S-23S rDNA internal spacer regions
      (ISR) as targets for PCR detection of Azospirillum ssp. and the phytostimulatory
      plant growth-promoting rhizobacteria seed inoculant Azospirillum lipoferum CRT1
      in soil. METHODS AND RESULTS: Primer sets were designed after sequence analysis
      of the ISR of A. lipoferum CRT1 and Azospirillum brasilense Sp245. The primers
      fAZO/rAZO targeting the Azospirillum genus successfully yielded PCR amplicons
      (400-550 bp) from Azospirillum strains but also from certain non-Azospirillum
      strains in vitro, therefore they were not appropriate to monitor indigenous
      Azospirillum soil populations. The primers fCRT1/rCRT1 targeting A. lipoferum
      CRT1 generated a single 249-bp PCR product but could also amplify other strains
      from the same species. However, with DNA extracts from the rhizosphere of field
      grown maize, both fAZO/rAZO and fCRT1/rCRT1 primer sets could be used to evidence
      strain CRT1 in inoculated plants by nested PCR, after a first ISR amplification
      with universal ribosomal primers. In soil, a 7-log dynamic range of detection
      (10(2)-10(8) CFU g(-1) soil) was obtained. CONCLUSIONS: The PCR primers targeting
      16S-23S rDNA ISR sequences enabled detection of the inoculant A. lipoferum CRT1
      in field soil. SIGNIFICANCE AND IMPACT OF THE STUDY: Convenient methods to
      monitor Azospirillum phytostimulators in the soil are lacking. The PCR protocols
      designed based on ISR sequences will be useful for detection of the crop
      inoculant A. lipoferum CRT1 under field conditions.

PMID- 19583801
TI  - Characterization of Chlamydiaceae species using PCR and high resolution melt
      curve analysis of the 16S rRNA gene.
AB  - AIM: To design a rapid diagnostic test to differentiate species belonging to the
      family Chlamydiaceae. METHODS AND RESULTS: Five oligonucleotide sets each
      targeting various conserved regions of the genome of six species (Chlamydia
      muridarum, C. suis, C. trachomatis, Chlamydophila felis, Cp. pneumoniae and Cp.
      psittaci) belonging to the family Chlamydiaceae were tested for their suitability
      for polymerase chain reaction (PCR) and high resolution melt (HRM) curve analysis
      to differentiate Chlamydiaceae species. Three of the oligonucleotide sets were
      able to detect all six reference species used in this study, but only one set
      (16SG) could clearly differentiate between them by HRM curve analysis. The PCR
      HRM curve analysis confidence percentages correlated strongly with the nucleotide
      sequence identities. Clinical specimens from a number of animal species suspected
      of chlamydiosis were tested with the newly developed 16SG PCR-HRM curve analysis
      and sequenced to confirm the infecting species. It was demonstrated that PCR-HRM
      using the 16SG oligonucleotide set could relate the infecting Chlamydiaceae
      species to the most similar (based on 16S rRNA gene nucleotide sequence)
      reference species tested. Although Cp. pecorum was not included initially as a
      reference species in this assay, inclusion of a field isolate of Cp. pecorum as a
      reference allowed two koala specimens to be correctly identified. CONCLUSION: PCR
      HRM analysis using the oligonucleotide set 16SG is a robust, simple and rapid
      technique for differentiation of at least the Chlamydiaceae species used in this
      study. SIGNIFICANCE AND IMPACT OF THE STUDY: This technique allowed for the rapid
      detection and identification of the six Chlamydiaceae reference species and may
      be useful for identification of uncharacterized Chlamydiaceae species or for use
      in animal species where occurrence of the disease has not been fully
      investigated.

PMID- 19583802
TI  - Calorimetric investigations into the starvation response of Pseudomonas putida
      growing on phenol and glucose.
AB  - AIMS: To investigate the stress response during nutrient deprivation,
      particularly with regard to the application of phenol as growth substrate of
      Pseudomonas putida with calorimetric measurements as a new method. METHODS AND
      RESULTS: The online and noninvasive measurement of the thermal power P(0) permits
      the detection of microbial activity during the starvation period. While the
      results of the investigations with phenol reveal a significant loss of activity
      as a function of the temporal nutrient dosage, only a small loss of activity was
      detected by using glucose. Microbiological methods (colony forming units (CFU)
      and activity of catechol-2,3-dioxygenase) showed a loss of the enzyme activity at
      a constant CFU. The introduction of a simple decay parameter k(D) in the kinetic
      description of the growth process on phenol was sufficient for the successful
      kinetic modelling. CONCLUSIONS: The combination of calorimetric measurements and
      the determination of the enzymatic activity proved the loss of activity of Ps.
      putida during the deprivation of the substrate phenol. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The initial heat power (P(0)) proves to be a suitable parameter for
      the characterization of the physiological state of the culture and can be used
      for the regulation of nutrient supply in biotechnological process development.

PMID- 19583803
TI  - HDAC inhibitor, scriptaid, induces glioma cell apoptosis through JNK activation
      and inhibits telomerase activity.
AB  - The present study identified a novel mechanism of induction of apoptosis in
      glioblastoma cells by scriptaid - a histone deacetylase (HDAC) inhibitor.
      Scriptaid reduced glioma cell viability by increasing Jun N-terminal kinase (JNK)
      activation. Although scriptaid induced activation of both p38MAPK and JNK, it was
      the inhibition of JNK that attenuated scriptaid-induced apoptosis significantly.
      Scriptaid also increased the expression of (i) p21 and p27 involved in cell-cycle
      regulation and (ii) gammaH2AX associated with DNA damage response in a JNK
      dependent manner. Treatment with scriptaid increased Ras activity in glioma
      cells, and transfection of cells with constitutively active RasV12 further
      sensitized glioma cells to scriptaid-induced apoptosis. Scriptaid also inhibited
      telomerase activity independent of JNK. Taken together, our findings indicate
      that scriptaid (i) induces apoptosis and reduces glioma cell proliferation by
      elevating JNK activation and (ii) also decreases telomerase activity in a JNK
      independent manner.

PMID- 19583804
TI  - Introduction to the tumour microenvironment review series.

PMID- 19583805
TI  - RNA-binding proteins implicated in the hypoxic response.
AB  - In cells responding to low oxygen levels, gene expression patterns are strongly
      influenced by post-transcriptional processes. RNA-binding proteins (RBPs) are
      pivotal regulators of gene expression in response to numerous stresses, including
      hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in
      response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB
      (polypyrimidine tract-binding protein) associate with mRNAs encoding hypoxia
      response proteins such as HIF-1alpha and VEGF mRNAs, enhance their expression
      after hypoxia and play a major role in establishing hypoxic gene expression
      patterns. Additional RBPs such as iron-response element-binding proteins (IRPs),
      cytoplasmic polyadenylation-element-binding proteins (CPEBs) and several
      heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia-regulated
      transcripts and modulate the levels of the encoded proteins. We discuss the
      efficient regulation of hypoxic gene expression by RBPs and the mounting interest
      in targeting hypoxia-regulatory RBPs in diseases with aberrant hypoxic responses.

PMID- 19583807
TI  - A novel recombinant immunotoxin with the smallest ribosome-inactivating protein
      Luffin P1: T-cell cytotoxicity and prolongation of allograft survival.
AB  - In the creation of stable tolerance to MHC-incompatible allografts, reducing the
      large mass of donor-reactive cells via apoptosis is often required. Apoptosis
      induction by immunotoxins targeting surface molecules specifically presented on
      donor-reactive cytopathic T effector (T(eff)) cells is a promising strategy.
      Traditionally, the toxin moieties are bacterial exotoxins or plant-derived
      ribosome-inactivating proteins (RIPs) with large molecular size and strong
      immunogenicity, hence causing the problems of tissue penetration, host immune
      reaction and quick clearance. We have identified a novel class of small molecule
      RIPs (<10 kD) from the seeds of the plant Luffa cylindrica. The smallest member
      of this family, Luffin P1, has a molecular weight of 5226.8 Da, yet possessing a
      highly potent inhibitory activity on cell-free protein synthesis with IC50 of
      0.88 nM. We now report a recombinant hIL-2-Luffin P1 immunotoxin, which strongly
      inhibited T-cell proliferation in mixed lymphocyte reaction and ConA response
      with IC50 of 1.8-10 nM. In vivo, hIL-2-Luffin P1 significantly prolonged the
      survival of major MHC-mismatched skin and kidney allografts in animal models.
      Thus, we demonstrate for the first time the efficacy of the smallest immunotoxin
      that could be further combined with other pharmacological and immunological
      reagents for synergistic control of pathogenic lymphocytes in immune-mediated
      diseases.

PMID- 19583806
TI  - Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in
      polycystic ovarian tissue.
AB  - Connective tissue components--collagen types I, III and IV--surrounding the
      ovarian follicles undergo drastic changes during ovulation. Abnormal collagen
      synthesis and increased volume and density of ovarian stroma characterize the
      polycystic ovary syndrome (PCOS). During the ovulatory process, collagen
      synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in
      ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays
      essential role in coordinating the control of ovarian extracellular matrix (ECM)
      during follicular development. We have recently shown accumulation of advanced
      glycation end products (AGEs), molecules that stimulate ECM production and
      abnormal collagen cross-linking, in ovarian tissue. However, the possible link
      between LOX and AGEs-induced signalling in collagen production and stroma
      formation in ovarian tissue from PCOS remains elusive. The present study
      investigates the hypothesis of AGE signalling pathway interaction with LOX gene
      activity in polycystic ovarian (PCO) tissue. We show an increased distribution
      and co-localization of LOX, collagen type IV and AGE molecules in the PCO tissue
      compared to control, as well as augmented expression of AGE signalling
      mediators/effectors, phospho(p)-ERK, phospho(p)-c-Jun and nuclear factor kappaB
      (NF-kappaB) in pathological tissue. Moreover, we demonstrate binding of AGE
      induced transcription factors, NF-kappaB and activator protein-1 (AP-1) on LOX
      promoter, indicating a possible involvement of AGEs in LOX gene regulation, which
      may account for the documented increase in LOX mRNA and protein levels compared
      to control. These findings suggest that deposition of excess collagen in PCO
      tissue that induces cystogenesis may, in part, be due to AGE-mediated stimulation
      of LOX activity.

PMID- 19583808
TI  - Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up
      regulation of an Akt-binding protein, periplakin.
AB  - Although overexpression of cyclin A2 is reportedly an indicator of a poor
      prognosis of various malignancies including endometrial carcinoma, its molecular
      mechanism remains undetermined. To address this issue, we examined the effect of
      cyclin A2 on the development of resistance to chemotherapeutic drugs. The
      expression of cyclin A2 protein was increased in advanced-stage and chemotherapy
      refractory stage endometrial carcinomas compared with that in early-stage
      tumours. The expression levels of cyclin A2 in endometrial carcinoma cell lines
      correlated positively with the IC(50) for cisplatin. Endometrial carcinoma HHUA
      cells that overexpressed cyclin A2 showed increased resistance to cisplatin in
      vitro and in vivo, via the activation of a survival pathway, the inositol-3
      phosphate kinase (PI3K) cascade. The use of a cDNA microarray identified an Akt
      binding protein, periplakin, as a novel target of cyclin A2. The cyclin A2
      induced up-regulation of periplakin was mediated via direct binding of Sp1 to the
      promoter that was activated by cyclin A2 along with chromatin remodelling
      involving CBP/p300, and the siRNA-mediated silencing of periplakin suppressed the
      PI3K pathway. These results indicate cyclin A2 to be involved in the acquisition
      of aggressive behaviour of tumour cells through the activation of PI3K by cyclin
      A2-induced periplakin, and to be a promising therapeutic target.

PMID- 19583809
TI  - Physiological concentrations of bile acids down-regulate agonist induced
      secretion in colonic epithelial cells.
AB  - In patients with bile acid malabsorption, high concentrations of bile acids enter
      the colon and stimulate Cl(-) and fluid secretion, thereby causing diarrhoea.
      However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally
      present at lower concentrations where its role in regulating transport is
      unclear. Thus, the current study set out to investigate the effects of
      physiologically relevant DCA concentrations on colonic epithelial secretory
      function. Cl(-) secretion was measured as changes in short-circuit current across
      voltage-clamped T(84) cell monolayers. At high concentrations (0.5-1 mM), DCA
      acutely stimulated Cl(-) secretion but this effect was associated with cell
      injury, as evidenced by decreased transepithelial resistance (TER) and increased
      lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to
      lower DCA concentrations (10-200 microM) inhibited responses to Ca(2+) and cAMP
      dependent secretagogues without altering TER, LDH release, or secretagogue
      induced increases in intracellular second messengers. Other bile acids -
      taurodeoxycholic acid, chenodeoxycholic acid and cholic acid - had similar
      antisecretory effects. DCA (50 microM) rapidly stimulated phosphorylation of the
      epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen
      activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis
      inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the
      MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest
      that, in contrast to its acute prosecretory effects at pathophysiological
      concentrations, lower, physiologically relevant, levels of DCA chronically down
      regulate colonic epithelial secretory function. On the basis of these data, we
      propose a novel role for bile acids as physiological regulators of colonic
      secretory capacity.

PMID- 19583811
TI  - Image-guided tissue engineering.
AB  - Replication of anatomic shape is a significant challenge in developing implants
      for regenerative medicine. This has lead to significant interest in using medical
      imaging techniques such as magnetic resonance imaging and computed tomography to
      design tissue engineered constructs. Implementation of medical imaging and
      computer aided design in combination with technologies for rapid prototyping of
      living implants enables the generation of highly reproducible constructs with
      spatial resolution up to 25 microm. In this paper, we review the medical imaging
      modalities available and a paradigm for choosing a particular imaging technique.
      We also present fabrication techniques and methodologies for producing cellular
      engineered constructs. Finally, we comment on future challenges involved with
      image guided tissue engineering and efforts to generate engineered constructs
      ready for implantation.

PMID- 19583810
TI  - The immune boundaries for stem cell based therapies: problems and prospective
      solutions.
AB  - Stem cells have fascinated the scientific and clinical communities for over a
      century. Despite the controversy that surrounds this field, it is clear that stem
      cells have the potential to revolutionize medicine. However, a number of
      significant hurdles still stand in the way of the realization of this potential.
      Chiefly among these are safety concerns, differentiation efficiency and
      overcoming immune rejection. Here we review current progress made in this field
      to optimize the safe use of stem cells with particular emphasis on prospective
      interventions to deal with challenges generated by immune rejection.

PMID- 19583812
TI  - Hyperacetylation in prostate cancer induces cell cycle aberrations, chromatin
      reorganization and altered gene expression profiles.
AB  - Histone acetylation is a fundamental mechanism in the regulation of local
      chromatin conformation and gene expression. Research has focused on the impact of
      altered epigenetic environments on the expression of specific genes and their
      pathways. However, changes in histone acetylation also have a global impact on
      the cell. In this study we used digital texture analysis to assess global
      chromatin patterns following treatment with trichostatin A (TSA) and have
      observed significant alterations in the condensation and distribution of higher
      order chromatin, which were associated with altered gene expression profiles in
      both immortalised normal PNT1A prostate cell line and androgen-dependent prostate
      cancer cell line LNCaP. Furthermore, the extent of TSA-induced disruption was
      both cell cycle and cell line dependent. This was illustrated by the
      identification of sub-populations of prostate cancer cells expressing high levels
      of H3K9 acetylation in the G(2)/M phase of the cell cycle that were absent in
      normal cell populations. In addition, the analysis of enriched populations of
      G(1) cells showed a global decondensation of chromatin exclusively in normal
      cells.

PMID- 19583814
TI  - Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and
      cell death: metallothionein protection.
AB  - We have shown cardiac protection by metallothionein (MT) in the development of
      diabetic cardiomyopathy (DCM) via suppression of cardiac cell death in cardiac
      specific MT-overexpressing transgenic (MT-TG) mice. The present study was
      undertaken to define whether diabetes can induce cardiac endoplasmic reticulum
      (ER) stress and whether MT can prevent cardiac cell death via attenuating ER
      stress. Diabetes was induced by streptozotocin in both MT-TG and wild-type (WT)
      mice. Two weeks, and 2 and 5 months after diabetes onset, cardiac ER stress was
      detected by expression of ER chaperones, and apoptosis was detected by
      CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and cleaved
      caspase-3 and caspase-12. Cardiac apoptosis in the WT diabetic mice, but not in
      MT-TG diabetic mice, was significantly increased 2 weeks after diabetes onset. In
      parallel with apoptotic effect, significant up-regulation of the ER chaperones,
      including glucose-regulated protein (GRP)78 and GRP94, cleaved ATF6 and
      phosporylated eIF2alpha, in the hearts of WT, but not MT-TG diabetic mice.
      Infusion of angiotensin II (Ang II) also significantly induced ER stress and
      apoptosis in the hearts of WT, but not in MT-TG mice. Direct administration of
      chemical ER stress activator tunicamycin significantly increased cardiac cell
      death only in WT mice. Pre-treatment with antioxidants completely prevented Ang
      II-induced ER stress and apoptosis in the cultured cardiac cells. These results
      suggest that ER stress exists in the diabetic heart, which may cause the cardiac
      cell death. MT prevents both diabetes- and Ang II-induced cardiac ER stress and
      associated cell death most likely via its antioxidant action, which may be
      responsible for MT's prevention of DCM.

PMID- 19583813
TI  - Lymphangiogenesis and cancer metastasis.
AB  - Metastasis is a characteristic trait of most tumour types and the cause for the
      majority of cancer deaths. Many tumour types, including melanoma and breast and
      prostate cancers, first metastasize via lymphatic vessels to their regional lymph
      nodes. Although the connection between lymph node metastases and shorter survival
      times of patients was made decades ago, the active involvement of the lymphatic
      system in cancer, metastasis has been unravelled only recently, after molecular
      markers of lymphatic vessels were identified. A growing body of evidence
      indicates that tumour-induced lymphangiogenesis is a predictive indicator of
      metastasis to lymph nodes and might also be a target for prevention of
      metastasis. This article reviews the current understanding of lymphangiogenesis
      in cancer anti-lymphangiogenic strategies for prevention and therapy of
      metastatic disease, quantification of lymphangiogenesis for the prognosis and
      diagnosis of metastasis and in vivo imaging technologies for the assessment of
      lymphatic vessels, drainage and lymph nodes.

PMID- 19583815
TI  - Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated
      protein accumulation.
AB  - Autophagy is an evolutionarily conserved cell survival pathway that enables cells
      to recoup ATP and other critical biosynthetic molecules during nutrient
      deprivation or exposure to hypoxia, which are hallmarks of the tumour
      microenvironment. Autophagy has been implicated as a potential mechanism of
      resistance to anticancer agents as it can promote cell survival in the face of
      stress induced by chemotherapeutic agents by breaking down cellular components to
      generate alternative sources of energy. Disruption of autophagy with chloroquine
      (CQ) induces the accumulation of ubiquitin-conjugated proteins in a manner
      similar to the proteasome inhibitor bortezomib (BZ). However, CQ-induced protein
      accumulation occurs at a slower rate and is localized to lysosomes in contrast to
      BZ, which stimulates rapid buildup of ubiquitinated proteins and aggresome
      formation in the cytosol. The histone deacetylase (HDAC) inhibitor vorinostat
      (VOR) blocked BZ-induced aggresome formation, but promoted CQ-mediated
      ubiquitinated protein accumulation. Disruption of autophagy with CQ strongly
      enhanced VOR-mediated apoptosis in colon cancer cells. Accordingly, knockdown of
      the essential autophagy gene Atg7 also sensitized cells to VOR-induced apoptosis.
      Knockdown of HDAC6 greatly enhanced BZ-induced apoptosis, but only marginally
      sensitized cells to CQ. Subsequent studies determined that the CQ/VOR combination
      promoted a large increase in superoxide generation that was required for
      ubiquitinated protein accumulation and cell death. Finally, treatment with the
      CQ/VOR combination significantly reduced tumour burden and induced apoptosis in a
      colon cancer xenograft model. Collectively, our results establish that inhibition
      of autophagy with CQ induces ubiquitinated protein accumulation and VOR
      potentiates CQ-mediated aggregate formation, superoxide generation and apoptosis.

PMID- 19583817
TI  - Functional polymorphism in H2BFWT-5'UTR is associated with susceptibility to male
      infertility.
AB  - H2B histone family, member W, testis-specific (H2BFWT) gene encodes a testis
      specific histone that becomes incorporated into sperm chromatin. A male
      infertility-associated single nucleotide polymorphism (-9C > T) within the 5'
      untranslated region (5'UTR) of the H2BFWT gene was identified by direct
      sequencing. Statistical association studies showed the polymorphism significantly
      associated with male infertility (n = 442, P = 0.0157), especially in non
      azoospermia (n = 262, P = 0.018). Furthermore, this polymorphism is also
      associated with sperm parameters, especially sperm count (n = 164, P = 0.0127)
      and vitality (n = 164, P = 0.0076). We investigated how the genetic variant at
      5'UTR confers susceptibility to non-azoospermia. Western blotting of His-tag
      H2BFWT revealed a difference at the translational level between -9T and the wild
      type -9C in the absence of change at the transcriptional level. Reporter assays
      showed that this reducing translational change originated from an upstream open
      reading frame (uORF) generated by the -9C to -9T change. Finally, in vivo H2BFWT
      expression in sperm was significantly dependent on the -9C > T genotype from non
      azoospermia (P = 0.0061). Therefore, this polymorphism could affect the
      translational efficiency of a quantitatively important histone protein by the
      uORF. Our data implicate H2BFWT as a susceptibility factor for male infertility,
      possibly with other genetic and environmental factors.

PMID- 19583818
TI  - Genetic variants associated with deep vein thrombosis: the F11 locus.
AB  - BACKGROUND: Recent studies have found associations between deep vein thrombosis
      (DVT) and single nucleotide polymorphisms (SNPs) in a 4q35.2 locus that contains
      genes encoding factor XI (F11), a cytochrome P450 family member (CYP4V2), and
      prekallikrein (KLKB1). OBJECTIVE: We investigated which of the common SNPs in
      this locus are independently associated with DVT. METHODS: The study populations
      were the Leiden Thrombophilia Study (LETS) (443 DVT cases and 453 controls) and
      the Multiple Environmental and Genetic Assessment of risk factors for venous
      thrombosis (MEGA study) (2712 DVT cases and 4634 controls). We assessed the
      association between DVT and 103 SNPs in a 200 kb region using logistic
      regression. RESULTS: We found that two SNPs (rs2289252 and rs2036914 in F11) were
      independently associated with DVT. After adjusting for age, sex, and the other
      SNP, the odds ratios (risk vs. non-risk homozygotes) of these two SNPs were 1.49
      for rs2289252 (95% CI, 1.25-1.76) and 1.33 for rs2036914 (95% CI, 1.11-1.59). We
      found that rs2289252 was also associated with FXI levels, as has been previously
      reported for rs2036914; these two SNPs remained associated with DVT with somewhat
      attenuated risk estimates after adjustment for FXI levels. CONCLUSION: Two SNPs,
      rs2289252 and rs2036914 in F11, appear to independently contribute to the risk of
      DVT, a contribution that is explained at least in part by an association with FXI
      levels.

PMID- 19583816
TI  - Histone deacetylase inhibition and the regulation of cell growth with particular
      reference to liver pathobiology.
AB  - The transcriptional activity of genes largely depends on the accessibility of
      specific chromatin regions to transcriptional regulators. This process is
      controlled by diverse post-transcriptional modifications of the histone amino
      termini of which reversible acetylation plays a vital role. Histone
      acetyltransferases (HATs) are responsible for the addition of acetyl groups and
      histone deacetylases (HDACs) catalyse the reverse reaction. In general, though
      not exclusively, histone acetylation is associated with a positive regulation of
      transcription, whereas histone deacetylation is correlated with transcriptional
      silencing. The elucidation of unequivocal links between aberrant action of HDACs
      and tumorigenesis lies at the base of key scientific importance of these enzymes.
      In particular, the potential benefit of HDAC inhibition has been confirmed in
      various tumour cell lines, demonstrating antiproliferative, differentiating and
      pro-apoptotic effects. Consequently, the dynamic quest for HDAC inhibitors (HDIs)
      as a new class of anticancer drugs was set off, resulting in a number of
      compounds that are currently evaluated in clinical trials. Ironically, the
      knowledge with respect to the expression pattern and function of individual HDAC
      isoenzymes remains largely elusive. In the present review, we provide an update
      of the current knowledge on the involvement of HDACs in the regulation of
      fundamental cellular processes in the liver, being the main site for drug
      metabolism within the body. Focus lies on the involvement of HDACs in the
      regulation of growth of normal and transformed hepatocytes and the
      transdifferentiation process of stellate cells. Furthermore, extrapolation of our
      present knowledge on HDAC functionality towards innovative treatment of malignant
      and non-malignant, hyperproliferative and inflammatory disorders is discussed.

PMID- 19583819
TI  - Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular
      events: four studies and a meta-analysis.
AB  - OBJECTIVE: The exposure of tissue factor (TF) to blood flow is the initial step
      in the coagulation process and plays an important role in thrombogenesis. We
      investigated the role of genetic polymorphisms and haplotypes of the TF gene in
      the risk of ischemic vascular disease. METHODS: Four hundred and twenty-two
      Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808
      US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic
      stroke and 209 controls and 148 German cases with juvenile ischemic stroke and
      191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population),
      rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped.
      Additionally, a meta-analysis of all previous studies on TF loci and the risk of
      ischemic coronary disease (ICD) was performed. RESULTS: After multivariable
      analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any
      consistent association with MI. Pooled meta-analysis of six studies also
      suggested that TF polymorphisms are not associated with CHD. A significant,
      independent association between SNP rs1324214 (C/T) and juvenile stroke was found
      in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24
      0.92, in combined analysis). Pooled analysis also showed a significant
      association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3
      H3 (OR = 0.43, 95% CI 0.20-0.92). CONCLUSIONS: TF genetic variations were
      associated with the risk of ischemic stroke at young age, but did not affect
      ischemic coronary disease.

PMID- 19583820
TI  - Levels of circulating endothelial progenitor cells are related to uremic toxins
      and vascular injury in hemodialysis patients.
AB  - BACKGROUND: Patients suffering from chronic kidney diseases (CKD) exhibit
      cardiovascular diseases and profound endothelial dysfunction. CKD patients have
      reduced numbers of endothelial progenitor cells, but little is known about the
      factors influencing these numbers. OBJECTIVES: Among these factors, we
      hypothesized that uremic toxins and vascular injury affect endothelial progenitor
      cells. PATIENTS/METHODS: Thirty-eight hemodialysis patients were investigated and
      compared with 21 healthy controls. CD34+CD133+ immature progenitors, CD34+KDR+
      endothelial progenitors cells (EPC) and myeloid EPC (mEPC) were counted in
      peripheral blood. Levels of uremic toxins beta(2)-microglobulin, indole-3 acetic
      acid, indoxylsulfate, p-cresylsulfate and homocysteine were measured. Vascular
      injury was assessed in hemodialysis (HD) patients by measuring aortic pulse wave
      velocity and plasma levels of endothelial microparticles. In vitro experiments
      were performed to study the effect of uremic toxins on apoptosis of progenitor
      cells. RESULTS AND CONCLUSIONS: CD34+CD133+ immature progenitor cell number was
      negatively correlated with the levels of uremic toxins beta(2)-microglobulin and
      indole-3 acetic acid. In vitro, indole-3 acetic acid induced apoptosis of CD133+
      cells. These data indicate uremic toxins have a deleterious role on progenitor
      cells, early in the differentiation process. Moreover, mEPC number was positively
      correlated with markers of vascular injury-pulse wave velocity and endothelial
      microparticle levels. This suggests that vascular lesions could stimulate
      progenitor cell mobilization, even in a context of reduced EPC induced by CKD. In
      conclusion, uremic toxins and vascular injury appear to affect endothelial
      progenitor cell biology in CKD.

PMID- 19583821
TI  - Evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of
      venous thromboembolism.

PMID- 19583822
TI  - The molecular mechanisms of immunomodulation and tolerance induction to factor
      VIII.
AB  - Successful factor (F) VIII replacement therapy in hemophilia A patients is
      confounded by the generation of inhibitory anti-FVIII antibodies (Ab) in 25-30%
      of treated patients. These antibodies, termed 'inhibitors', significantly
      increase morbidity within the hemophilia population and lower the quality of life
      for these patients. For the past 30 years, immune tolerance induction (ITI) has
      been the standard therapy to elicit immunological tolerance to FVIII in the
      clinic. ITI works well in approximately 75% of patients, but it is expensive, can
      take years to show effect and is in many cases practically challenging.
      Therefore, new immunological tolerance induction strategies are now being
      designed and tested in hemophilia A animal models. This review attempts to
      provide a comprehensive description, at both the cellular and molecular levels,
      of these novel advances in tolerance induction and immunomodulation of FVIII. We
      begin by briefly reviewing why and how the immune system generates a protective
      response against exogenous FVIII. This leads to a discussion of the latest
      advances in FVIII tolerance/immunomodulation technology. These advances include
      interesting methodologies to induce B cell specific tolerance in FVIII primed
      humans and animals, as well as newer T cell-specific therapies that modify and/or
      block co-stimulation. We also discuss methods to manipulate FVIII loading of
      antigen-presenting cells.

PMID- 19583823
TI  - An acquired inhibitor to the GPVI platelet collagen receptor in a patient with
      lupus nephritis.
AB  - BACKGROUND: GPVI is a major platelet collagen signaling receptor. In rare cases
      of immune thrombocytopenic purpura (ITP), autoantibodies to GPVI result in
      receptor shedding. OBJECTIVES: To investigate a possible pathogenic role of
      plasma anti-GPVI antibody located in a woman with lupus nephritis. METHODS:
      Measured were (i) platelet aggregation to collagen and convulxin, (ii) platelet
      GPVI expression (flow cytometry and western blotting), (iii) plasma soluble GPVI
      (sGPVI, dual antibody ELISA), and (iv) plasma anti-GPVI antibody (ELISA using
      recombinant sGPVI). RESULTS: In 2006 and early 2007, the patient had a normal
      platelet count but a virtual absence of platelet aggregation to collagen and
      convulxin. Her platelets responded normally to other agonists including cross
      linking ITAM-dependent FcgammaRIIA by monoclonal antibody, IV.3. Flow cytometry
      and western blotting showed a platelet deficiency of GPVI. Plasma sGPVI levels
      were undetectable whereas ELISA confirmed the presence of anti-GPVI antibody.
      Sequencing revealed a normal GPVI cDNA structure. The patient's plasma and the
      isolated IgG3 fraction activated and induced GPVI shedding from normal platelets.
      A deteriorating clinical condition led to increasingly strict immunosuppressive
      therapy. This was globally associated with a fall in plasma anti-GPVI titres, the
      restoration of platelet GPVI and the convulxin response, and the loss of her
      nephrotic syndrome. CONCLUSIONS: Our results show that this patient acquired a
      potent anti-GPVI IgG3 antibody with loss of GPVI and collagen-related platelet
      function. Further studies are required to determine whether anti-GPVI antibodies
      occur in other lupus patients with nephritis.

PMID- 19583824
TI  - Prophylactic immune tolerance induced by changing the ratio of antigen-specific
      effector to regulatory T cells.
AB  - BACKGROUND: Gene and protein replacement therapies for inherited protein
      deficiencies such as hemophilia or lysosomal storage disorders are limited by
      deleterious immune responses directed against their respective therapeutic
      proteins. Therefore, the development of protocols preventing such responses is
      key to providing successful long-term therapy. OBJECTIVES: We sought to develop a
      protocol, utilizing a drug/peptide cocktail, that would effectively shift the
      antigen-specific CD4+ T-cell population, tipping the balance from effector T
      cells (Teffs) towards regulatory T cells (Tregs). METHODS: Treg-deficient
      (DO11.10-tg Rag2(-/-)) BALB/c mice were used to screen for an optimal protocol
      addressing the aforementioned goal and to study the mechanisms underlying in vivo
      changes in T-cell populations. Muscle-directed gene transfer to hemophilia B mice
      was also performed in order to test the optimal protocol in a therapeutically
      relevant setting. RESULTS: Specific antigen administration (4-week repeated
      dosing) combined with rapamycin and interleukin-10 led to substantial reductions
      in Teffs, via activation-induced cell death, and induced CD4+CD25+FoxP3+ Tregs to
      a large extent in multiple organs. The proportion of apoptotic T cells also
      increased over time, whereas Teffs and Tregs were differentially affected. When
      applied to a model of protein deficiency (gene therapy for hemophilia B), the
      protocol successfully prevented inhibitor formation, whereas non-specific
      immunosuppression was only marginally effective. CONCLUSIONS: It is feasible to
      provide a short-term, prophylactic protocol allowing for the induction of immune
      tolerance. This protocol may provide a marked advance in efforts seeking to
      improve clinical outcomes in disorders involving therapeutic protein replacement.

PMID- 19583825
TI  - A modified recombinant factor VIIa: can we make it work harder, better, faster,
      stronger?

PMID- 19583826
TI  - Abnormal hemostasis in a knock-in mouse carrying a variant of factor IX with
      impaired binding to collagen type IV.
AB  - BACKGROUND: Factor IX binds to collagen type IV, but this binding has no known
      consequence. OBJECTIVES: To determine the effect of reduced binding of FIX to
      collagen IV. METHODS: We constructed and characterized 'knock-in' mice containing
      the mutation lysine 5 to alanine (K5A) in the Gla domain of their FIX. The K5A
      mutation dramatically reduced the affinity of FIX for collagen type IV, but had
      no measurable effect on platelet binding, phospholipid binding, or in vitro
      clotting activity. However, K5AFIX mice had a mild bleeding tendency, despite
      their in vitro clotting activity being normal. Hemostatic protection from delayed
      rebleeding was intermediate between wild-type and hemophilia B mice (which had no
      detectable clotting activity); moreover, survival of K5A FIX mice after nascent
      clot removal was dramatically improved as compared with hemophilia B mice.
      Importantly, there was no detectable difference between K5AFIX and wild-type mice
      in either a laser-induced thrombosis model or the chromogenic FIX activity assay.
      In contrast, after ferric chloride injury, which exposes collagen IV as well as
      other basement membrane proteins, intravital microscopy revealed that vessel
      occlusion was significantly slower in K5AFIX mice than in wild-type mice.
      CONCLUSIONS: Our results indicate that the FIX molecule with decreased affinity
      for collagen IV has altered hemostatic properties in vivo and that the binding of
      FIX to collagen IV probably plays a significant functional role in hemostasis.

PMID- 19583827
TI  - The genetics of isolated orofacial clefts: from genotypes to subphenotypes.
AB  - Orofacial clefts are the most common craniofacial birth defects and one of the
      most common congenital malformations in humans. They require complex
      multidisciplinary treatment and are associated with elevated infant mortality and
      significant lifelong morbidity. The development of craniofacial structures is an
      exquisitely orchestrated process involving the coordinated growth of multiple,
      independently derived primordia. Perturbations impacting on the genesis or growth
      of these primordia may interfere with the proper morphogenesis of facial
      structures, resulting in clefting of the lip, the primary or secondary palate, or
      a combination of these sites. A variety of genetic approaches involving both
      human populations and animal models have greatly facilitated the search for genes
      involved in human clefting. In this article, we review the most prominent genes
      for orofacial clefts in the context of developmental pathways that shape the
      craniofacial complex. We highlight several Mendelian clefting syndromes that have
      provided valuable clues in identifying genes for the more common, isolated forms
      of clefting. Finally, we elaborate on a number of potential subclinical features
      (subphenotypes) associated with what have previously been diagnosed as 'isolated'
      clefts that may serve as additional markers for identifying individuals or
      families in whom there may be a greater risk of inheriting a cleft.

PMID- 19583828
TI  - Extraintestinal pathogenic Escherichia coli O1:K1:H7/NM from human and avian
      origin: detection of clonal groups B2 ST95 and D ST59 with different host
      distribution.
AB  - BACKGROUND: Extraintestinal pathogenic Escherichia coli (ExPEC) strains of
      serotype O1:K1:H7/NM are frequently implicated in neonatal meningitis, urinary
      tract infections and septicemia in humans. They are also commonly isolated from
      colibacillosis in poultry. Studies to determine the similarities of ExPEC from
      different origins have indicated that avian strains potentially have zoonotic
      properties. RESULTS: A total of 59 ExPEC O1:K1:H7/NM isolates (21 from avian
      colibacillosis, 15 from human meningitis, and 23 from human urinary tract
      infection and septicemia) originated from four countries were characterized by
      phylogenetic PCR grouping, Multilocus Sequence Typing (MLST), Pulsed Field Gel
      Electrophoresis (PFGE) and genotyping based on several genes known for their
      association with ExPEC or avian pathogenic Escherichia coli (APEC) virulence.APEC
      and human ExPEC isolates differed significantly in their assignments to
      phylogenetic groups, being phylogroup B2 more prevalent among APEC than among
      human ExPEC (95% vs. 53%, P = 0.001), whereas phylogroup D was almost exclusively
      associated with human ExPEC (47% vs. 5%, P = 0.0000). Seven virulence genes
      showed significant differences, being fimAvMT78 and sat genes linked to human
      isolates, while papGII, tsh, iron, cvaC and iss were significantly associated to
      APEC. By MLST, 39 of 40 ExPEC belonging to phylogroup B2, and 17 of 19 belonging
      to phylogroup D exhibited the Sequence Types (STs) ST95 and ST59, respectively.
      Additionally, two novel STs (ST1013 and ST1006) were established. Considering
      strains sharing the same ST, phylogenetic group, virulence genotype and PFGE
      cluster to belong to the same subclone, five subclones were detected; one of
      those grouped six strains of human and animal origin from two countries.
      CONCLUSION: Present results reveal that the clonal group B2 O1:K1:H7/NM ST95,
      detected in strains of animal and human origin, recovered from different dates
      and geographic sources, provides evidence that some APEC isolates may act as
      potential pathogens for humans and, consequently, poultry as a foodborne source,
      suggesting no host specificity for this type of isolates. A novel and important
      finding has been the detection of the clonal group D O1:K1:H7/NM ST59 almost
      exclusively in humans, carrying pathogenic genes linked to the phylogenetic group
      D. This finding would suggest D O1:K1:H7/NM ST59 as a host specific pathotype for
      humans.

PMID- 19583829
TI  - Correction: Ethnic differences in BMI among Dutch adolescents: what is the role
      of screen viewing, active commuting to school, and consumption of soft drinks and
      high-caloric snacks?

PMID- 19583830
TI  - Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the
      immunologic facet of oncolytic therapy.
AB  - BACKGROUND: GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that
      selectively colonizes established human xenografts inducing their complete
      regression. RESULTS: Here, we explored xenograft/VACV/host interactions in vivo
      adopting organism-specific expression arrays and tumor cell/VACV in vitro
      comparing VACV replication patterns. There were no clear-cut differences in vitro
      among responding and non-responding tumors, however, tumor rejection was
      associated in vivo with activation of interferon-stimulated genes (ISGs) and
      innate immune host's effector functions (IEFs) correlating with VACV colonization
      of the xenografts. These signatures precisely reproduce those observed in humans
      during immune-mediated tissue-specific destruction (TSD) that causes tumor or
      allograft rejection, autoimmunity or clearance of pathogens. We recently defined
      these common pathways in the "immunologic constant of rejection" hypothesis
      (ICR). CONCLUSION: This study provides the first prospective validation of a
      universal mechanism associated with TSD. Thus, xenograft infection by oncolytic
      VACV, beyond offering a promising therapy of established cancers, may represent a
      reliable pre-clinical model to test therapeutic strategies aimed at modulating
      the central pathways leading to TSD; this information may lead to the
      identification of principles that could refine the treatment of cancer and
      chronic infection by immune stimulation or autoimmunity and allograft rejection
      through immune tolerance.

PMID- 19583831
TI  - Excitatory repetitive transcranial magnetic stimulation to left dorsal premotor
      cortex enhances motor consolidation of new skills.
AB  - BACKGROUND: Following practice of skilled movements, changes continue to take
      place in the brain that both strengthen and modify memory for motor learning.
      These changes represent motor memory consolidation a process whereby new memories
      are transformed from a fragile to a more permanent, robust and stable state. In
      the present study, the neural correlates of motor memory consolidation were
      probed using repetitive transcranial magnetic stimulation (rTMS) to the dorsal
      premotor cortex (PMd). Participants engaged in four days of continuous tracking
      practice that immediately followed either excitatory 5 HZ, inhibitory 1 HZ or
      control, sham rTMS. A delayed retention test assessed motor learning of repeated
      and random sequences of continuous movement; no rTMS was applied at retention.
      RESULTS: We discovered that 5 HZ excitatory rTMS to PMd stimulated motor memory
      consolidation as evidenced by off-line learning, whereas only memory
      stabilization was noted following 1 Hz inhibitory or sham stimulation.
      CONCLUSION: Our data support the hypothesis that PMd is important for continuous
      motor learning, specifically via off-line consolidation of learned motor
      behaviors.

PMID- 19583832
TI  - Inactivation of murine norovirus by chemical biocides on stainless steel.
AB  - BACKGROUND: Human norovirus (NoV) causes more than 80% of nonbacterial
      gastroenteritis in Europe and the United States. NoV transmission via
      contaminated surfaces may be significant for the spread of viruses. Therefore,
      measures for prevention and control, such as surface disinfection, are necessary
      to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a
      surrogate for human NoV was used to study the efficacy of active ingredients of
      chemical disinfectants for virus inactivation on inanimate surfaces. METHODS: The
      inactivating properties of different chemical biocides were tested in a
      quantitative carrier test with stainless steel discs without mechanical action.
      Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic
      acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of
      residual virus was determined by endpoint-titration on RAW 264.7 cells. RESULTS:
      PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)]
      were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by
      > or = 4 log10 within 5 minutes exposure time, whereas 2-propanol showed a
      reduced effectiveness even at 60% (v/v). Furthermore, there were no significant
      differences in virus reduction whatever interfering substances were used. When
      testing with ethanol, 1- and 2-propanol, results under clean conditions were
      nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3%
      erythrocytes). CONCLUSION: Products based upon PAA, GDA, ethanol and 1-propanol
      should be used for NoV inactivation on inanimate surfaces. Our data provide
      valuable information for the development of strategies to control NoV
      transmission via surfaces.

PMID- 19583833
TI  - Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to
      tumorigenesis.
AB  - The execution of the mitotic program with high fidelity is dependent upon
      precise spatiotemporal regulation of posttranslational protein modifications. For
      example, the timely polyubiquitination of critical mitotic regulators by Anaphase
      Promoting Complex/Cyclosome (APC/C) is essential for the metaphase to anaphase
      transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled
      activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of
      kinetochores to mitotic spindle and facilitating equal segregation of sister
      chromatids. The critical effector of the spindle checkpoint, Mitotic arrest
      deficient 2 (Mad2), is recruited to unattached kinetochores forming a complex
      with other regulatory proteins to efficiently and cooperatively inhibit APC/C
      Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the
      development of genomic instability in both cell culture and animal models, and
      evidence suggests that aberrant regulation of the spindle checkpoint plays a
      critical role in human carcinogenesis. Recent studies have illuminated a network
      of both degradative and non-degradative ubiquitination events that regulate the
      metaphase to anaphase transition and mitotic exit. Within this context, our
      recent work showed that the HECT (Homologous to E6-AP C-terminus)-family E3
      ligase Smurf2 (Smad specific ubiquitin regulatory factor 2), known as a negative
      regulator of transforming growth factor-beta (TGF-beta) signaling, is required
      for a functional spindle checkpoint by promoting the functional localization and
      stability of Mad2. Here we discuss putative models explaining the role of Smurf2
      as a new regulator in the spindle checkpoint. The dynamic mitotic localization of
      Smurf2 to the centrosome and other critical mitotic structures provides
      implications about mitotic checkpoint control dependent on various ubiquitination
      events. Finally, deregulated Smurf2 activity may contribute to carcinogenesis by
      perturbed mitotic control.

PMID- 19583834
TI  - Higher percentage of CD133+ cells is associated with poor prognosis in colon
      carcinoma patients with stage IIIB.
AB  - BACKGROUND: Cancer stem cell model suggested that tumor progression is driven by
      the overpopulation of cancer stem cells and eradicating or inhibiting the
      symmetric division of cancer stem cells would become the most important
      therapeutic strategy. However, clinical evidence for this hypothesis is still
      scarce. To evaluate the overpopulation hypothesis of cancer stem cells the
      association of percentage of CD133+ tumor cells with clinicopathological
      parameters in colon cancer was investigated since CD133 is a putative cancer stem
      cell marker shared by multiple solid tumors. PATIENTS AND METHODS: Tumor tissues
      matched with adjacent normal tissues were collected from 104 stage IIIB colon
      cancer patients who were subject to radical resection between January, 1999 to
      July, 2003 in this center. The CD133 expression was examined with
      immunohistochemical staining. The correlation of the percentage of CD133+ cell
      with clinicopathological parameters and patients' 5-year survival was analyzed.
      RESULTS: The CD133+ cells were infrequent and heterogeneous distribution in the
      cancer tissue. Staining of CD133 was localized not only on the glandular-luminal
      surface of cancer cells but also on the invasive budding and the poorly
      differentiated tumors with ductal structures. Both univariate and multivariate
      survival analysis revealed that the percentage of CD133+ cancer cells and the
      invasive depth of tumor were independently prognostic. The patients with a lower
      percentage of CD133+ cancer cells (less than 5%) were strongly associated with a
      higher 5-year survival rate than those with a higher percentage of CD133+ cancer
      cells (greater than or equal to 55%). Additionally, no correlation was obtained
      between the percentage of CD133+ cancer cells and the other clinicopathological
      parameters including gender, age, site of primary mass, pathologic types, grades,
      and invasive depth. CONCLUSION: The fact that a higher percentage CD133+ cells
      were strongly associated with a poorer prognosis in patients with locally
      advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor
      progression, and the overpopulation hypothesis of cancer stem cell seems
      reasonable.

PMID- 19583836
TI  - The impact of platelet function or C-reactive protein, on cardiovascular events
      after an acute myocardial infarction.
AB  - BACKGROUND: Recurrent cardiovascular events following acute myocardial infarction
      (AMI) are common. The purpose of this study was to evaluate the impact of
      platelet aggregation, PFA-100 closure times and peak C-reactive protein (CRP),
      respectively, on the occurrence of death, myocardial infarction and ischemic
      cerebral events after an AMI. Furthermore, to examine the relationship between
      the platelet function tests and peak CRP. METHODS: Three hundred and thirty-four
      patients with AMI were included in the study. Platelet aggregation was analyzed
      by an aggregometer using laser light (PA-200). The state of high residual
      platelet reactivity was defined as normal closure times (PFA-100) during
      treatment with aspirin. RESULTS: The fourth quartile of peak CRP was associated
      with poorer outcome as compared to the first quartile in a multivariate Cox
      regression analysis, with a hazard ratio of 2.0 (95% CI 1.1-3.7) for the
      occurrence of death, myocardial infarction and ischemic cerebral events. The
      fourth quartile of peak CRP (>64.6 mg/l) was associated with platelet aggregation
      (p < 0.001, adjusted R2 = 0.13) and high residual platelet reactivity, in a
      multivariate model, with an odds ratio of 2.9 (CI 95% 1.3-6.8), as compared to
      the first quartile. Neither the highest quartile of platelet aggregation nor the
      state of high residual platelet reactivity predicted new cardiovascular events.
      CONCLUSION: In patients with myocardial infarction, measured peak CRP is
      associated with new cardiovascular events. Despite an association with peak CRP
      neither more pronounced platelet aggregation nor PFA-100 closure times
      independently predict new cardiovascular events.

PMID- 19583835
TI  - Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with
      the insect pathogen Photorhabdus luminescens.
AB  - BACKGROUND: The Gram-negative bacterium Photorhabdus asymbiotica (Pa) has been
      recovered from human infections in both North America and Australia. Recently, Pa
      has been shown to have a nematode vector that can also infect insects, like its
      sister species the insect pathogen P. luminescens (Pl). To understand the
      relationship between pathogenicity to insects and humans in Photorhabdus we have
      sequenced the complete genome of Pa strain ATCC43949 from North America. This
      strain (formerly referred to as Xenorhabdus luminescens strain 2) was isolated in
      1977 from the blood of an 80 year old female patient with endocarditis, in
      Maryland, USA. Here we compare the complete genome of Pa ATCC43949 with that of
      the previously sequenced insect pathogen P. luminescens strain TT01 which was
      isolated from its entomopathogenic nematode vector collected from soil in
      Trinidad and Tobago. RESULTS: We found that the human pathogen Pa had a smaller
      genome (5,064,808 bp) than that of the insect pathogen Pl (5,688,987 bp) but that
      each pathogen carries approximately one megabase of DNA that is unique to each
      strain. The reduced size of the Pa genome is associated with a smaller diversity
      in insecticidal genes such as those encoding the Toxin complexes (Tc's), Makes
      caterpillars floppy (Mcf) toxins and the Photorhabdus Virulence Cassettes (PVCs).
      The Pa genome, however, also shows the addition of a plasmid related to pMT1 from
      Yersinia pestis and several novel pathogenicity islands including a novel Type
      Three Secretion System (TTSS) encoding island. Together these data suggest that
      Pa may show virulence against man via the acquisition of the pMT1-like plasmid
      and specific effectors, such as SopB, that promote its persistence inside human
      macrophages. Interestingly the loss of insecticidal genes in Pa is not reflected
      by a loss of pathogenicity towards insects. CONCLUSION: Our results suggest that
      North American isolates of Pa have acquired virulence against man via the
      acquisition of a plasmid and specific virulence factors with similarity to those
      shown to play roles in pathogenicity against humans in other bacteria.

PMID- 19583837
TI  - Expressional dynamics of minisatellite 33.15 tagged spermatozoal transcriptome in
      Bubalus bubalis.
AB  - BACKGROUND: Transcriptionally quiescent spermatozoa have been established to be a
      repository of mRNA coding for several functionally essential cellular proteins.
      This entourage of mRNA is envisaged to be involved in post-fertilization and
      early embryogenesis. Minisatellites tagged with mRNA transcripts have been
      implicated with gene organization, regulation and function. However, the
      organization and expression of the minisatellite tagged transcript diversity,
      particularly in spermatozoa, remains unclear. RESULTS: In the present study, we
      identified and characterized 12 mRNA transcripts from the spermatozoa of water
      buffalo Bubalus bubalis employing minisatellite associated sequence amplification
      (MASA) and a consensus sequence of 33.15 repeat loci. Of these 33.15 tagged
      transcripts, only one was found to be homologous to Bovine steroid 21-hydroxylase
      (P-450-c21) gene. Other ten transcripts showed significant similarity with
      various mRNAs or chromosomal contigs across the species. The remaining one
      construed to be novel since this was unreported in the database (NCBI GenBank).
      All these uncharacterized and known transcripts showed highest expression in
      testis and spermatozoa compared to that in somatic tissues and ovary. Of these 12
      mRNA transcripts, 4 showed differential expression in the forebrain and hindbrain
      of buffalo. Moreover, genes corresponding to all the 33.15 tagged spermatozoal
      transcripts were found to be conserved across 13 other species analyzed.
      CONCLUSION: Our results show MASA as an important tool to capture mRNA transcript
      diversity tagged with minisatellites in the spermatozoa. Comprehensive
      characterization of these transcripts is envisaged to augment our understanding
      on the genes involved in testicular functions and sustenance of a viable paternal
      genome during pre- and post- fertilization events and early stages of
      development. Prospects of this approach in genome analysis in general and
      comparative genomics in particular are highlighted.

PMID- 19583838
TI  - The use of average Pavlov ratio to predict the risk of post operative upper limb
      palsy after posterior cervical decompression.
AB  - STUDY DESIGN: A retrospective study was conducted to study the post operative
      upper limb palsy after laminoplasty for cervical myelopathy. OBJECTIVE: To
      identify a reliable and simple preoperative radiological parameter in predicting
      the risk of post operative upper limb palsy. BACKGROUND: Post operative upper
      limb palsy is one of the causes of patient dissatisfaction after surgery. There
      had been no simple, standard preoperative radiological parameters reliably
      predict the occurrence of this problem. MATERIALS AND METHODS: Seventy-four
      patients received posterior cervical decompression from 1998 to 2008. Medical
      record and preoperative radiological information were evaluated. Clinical
      presentations of the palsy were described. The relationship between the
      occurrence of palsy and different preoperative radiological information is
      analyzed. RESULTS: Eighteen patients (24.3%) presented with post operative upper
      limb palsy. Majority of patients presented with dysesthesia (17/18) and with
      deficit of the C5 segment (17/18). Ten patients presented with pure dysesthesia
      and 8 patients presented with mixed motor-sensory deficit and dysesthesia.
      Multilevel involvement was exclusively presented in patients with motor weakness.
      A longer duration of symptom (16.7 Vs 57.2 days) was noticed in patients in the
      motor deficit group. Average Pavlov ratio less then 0.65 (P = 0.027, Odds Ratio =
      3.68) and compression at the C3/4 in preoperative MRI image (P = 0.025, Odds
      Ratio = 6) were significant risk factors for development of this problem.
      CONCLUSION: Post operative upper limb palsy is not uncommon and thorough
      preoperative explanation is important. There is a spectrum of clinical
      presentation and patients with multi-level involvement and motor deficit are
      associated with poorer prognosis. Average Pavlov ratio < 0.65 and compression at
      C3/4 segment on preoperative MRI image are simple and reliable preoperative
      predictor for the development of this problem.

PMID- 19583840
TI  - Trypanocidal activity of the proteasome inhibitor and anti-cancer drug
      bortezomib.
AB  - The proteasome inhibitor and anti-cancer drug bortezomib was tested for in vitro
      activity against bloodstream forms of Trypanosoma brucei. The concentrations of
      bortezomib required to reduce the growth rate by 50% and to kill all trypanosomes
      were 3.3 nM and 10 nM, respectively. In addition, bortezomib was 10 times more
      toxic to trypanosomes than to human HL-60 cells. Moreover, exposure of
      trypanosomes to 10 nM bortezomib for 16 h was enough to kill 90% of the parasites
      following incubation in fresh medium. However, proteasomal peptidase activities
      of trypanosomes exposed to bortezomib were only inhibited by 10% and 30%
      indicating that the proteasome is not the main target of the drug. The results
      suggest that bortezomib may be useful as drug for the treatment of human African
      trypanosomiasis.

PMID- 19583839
TI  - OHMM: a Hidden Markov Model accurately predicting the occupancy of a
      transcription factor with a self-overlapping binding motif.
AB  - BACKGROUND: DNA sequence binding motifs for several important transcription
      factors happen to be self-overlapping. Many of the current regulatory site
      identification methods do not explicitly take into account the overlapping sites.
      Moreover, most methods use arbitrary thresholds and fail to provide a biophysical
      interpretation of statistical quantities. In addition, commonly used approaches
      do not include the location of a site with respect to the transcription start
      site (TSS) in an integrated probabilistic framework while identifying sites.
      Ignoring these features can lead to inaccurate predictions as well as incorrect
      design and interpretation of experimental results. RESULTS: We have developed a
      tool based on a Hidden Markov Model (HMM) that identifies binding location of
      transcription factors with preference for self-overlapping DNA motifs by
      combining the effects of their alternative binding modes. Interpreting HMM
      parameters as biophysical quantities, this method uses the occupancy probability
      of a transcription factor on a DNA sequence as the discriminant function, earning
      the algorithm the name OHMM: Occupancy via Hidden Markov Model. OHMM learns the
      classification threshold by training emission probabilities using unaligned
      sequences containing known sites and estimating transition probabilities to
      reflect site density in all promoters in a genome. While identifying sites, it
      adjusts parameters to model site density changing with the distance from the
      transcription start site. Moreover, it provides guidance for designing padding
      sequences in gel shift experiments. In the context of binding sites to
      transcription factor NF-kappaB, we find that the occupancy probability predicted
      by OHMM correlates well with the binding affinity in gel shift experiments. High
      evolutionary conservation scores and enrichment in experimentally verified
      regulated genes suggest that NF-kappaB binding sites predicted by our method are
      likely to be functional. CONCLUSION: Our method deals specifically with
      identifying locations with multiple overlapping binding sites by computing the
      local occupancy of the transcription factor. Moreover, considering OHMM as a
      biophysical model allows us to learn the classification threshold in a principled
      manner. Another feature of OHMM is that we allow transition probabilities to
      change with location relative to the TSS. OHMM could be used to predict physical
      occupancy, and provides guidance for proper design of gel-shift experiments.
      Based upon our predictions, new insights into NF-kappaB function and regulation
      and possible new biological roles of NF-kappaB were uncovered.

PMID- 19583843
TI  - GOGrapher: A Python library for GO graph representation and analysis.
AB  - BACKGROUND: The Gene Ontology is the most commonly used controlled vocabulary for
      annotating proteins. The concepts in the ontology are organized as a directed
      acyclic graph, in which a node corresponds to a biological concept and a directed
      edge denotes the parent-child semantic relationship between a pair of terms. A
      large number of protein annotations further create links between proteins and
      their functional annotations, reflecting the contemporary knowledge about
      proteins and their functional relationships. This leads to a complex graph
      consisting of interleaved biological concepts and their associated proteins. What
      is needed is a simple, open source library that provides tools to not only create
      and view the Gene Ontology graph, but to analyze and manipulate it as well. Here
      we describe the development and use of GOGrapher, a Python library that can be
      used for the creation, analysis, manipulation, and visualization of Gene Ontology
      related graphs. FINDINGS: An object-oriented approach was adopted to organize the
      hierarchy of the graphs types and associated classes. An Application Programming
      Interface is provided through which different types of graphs can be
      pragmatically created, manipulated, and visualized. GOGrapher has been
      successfully utilized in multiple research projects, e.g., a graph-based multi
      label text classifier for protein annotation. CONCLUSION: The GOGrapher project
      provides a reusable programming library designed for the manipulation and
      analysis of Gene Ontology graphs. The library is freely available for the
      scientific community to use and improve.

PMID- 19583841
TI  - Increased levels of active c-Src distinguish invasive from in situ lobular
      lesions.
AB  - INTRODUCTION: Mounting molecular evidence suggests that invasive lobular
      carcinoma (ILC) is developing from in situ lesions, atypical lobular hyperplasia
      (ALH), and lobular carcinoma in situ (LCIS). However, little is known about the
      mechanisms promoting the progression of lobular breast cancer (LBC) to invasive
      disease. Here, we investigated whether c-Src kinase, an established inducer of
      invasive states, contributes to the progression from ALH/LCIS to ILC. METHODS:
      Immunochemistry for c-Src and other cancer-related molecules was performed on
      archived tissue specimens from 57 LBC patients. Relative c-Src activity was
      estimated by comparing fluorescence intensity of ILC with that of adjacent
      ALH/LCIS and nonneoplastic epithelia after staining with an antibody against
      active c-Src. Expression of active c-Src was correlated with markers of invasion
      and malignancy and with relapse among LBC patients. RESULTS: Levels of activated
      c-Src were increased in ILC relative to ALH/LCIS (1.63-fold +/- 0.24 SD) and
      nonneoplastic epithelia (1.47 +/- 0.18 SD). Increased c-Src levels correlated
      with the activation of c-Src downstream targets (Fak, Stat-3) and the expression
      of mesenchymal markers. ILC cells with activated c-Src co-expressed metastatic
      markers (Opn, Cxcr4) and included cells positive for the cancer stem cell marker
      Aldh1. A tendency for high c-Src levels (P = 0.072) was observed among the seven
      LBC patients with relapsed disease. CONCLUSIONS: Our data indicate elevated c-Src
      activity in ILC relative to noninvasive neoplastic tissue. The associated
      molecular changes suggest that c-Src promotes LBC invasiveness by inducing an
      epithelial-mesenchymal transition. Therefore, c-Src antagonists might counteract
      the acquisition of invasiveness during LBC progression. Inhibition of c-Src may
      also affect ILC cells thought to have a high metastatic potential and to be
      capable of initiating/maintaining tumor growth. Together with the possible
      association between high c-Src levels and disease recurrence, our findings
      encourage the evaluation of c-Src antagonists for the treatment of LBC.

PMID- 19583842
TI  - Evolutionary flexibility of protein complexes.
AB  - BACKGROUND: Proteins play a key role in cellular life. They do not act alone but
      are organised in complexes. Throughout the life of a cell, complexes are dynamic
      in their composition due to attachments and shared components. Experimental and
      computational evidence indicate that consecutive addition and secondary losses of
      components played a major role in the evolution of some complexes, mostly without
      affecting the core function. Here, we analysed in a large scale approach whether
      this flexibility in evolution is only limited to a distinct number of complexes
      or represents a more general trend. RESULTS: Focussing on human protein
      complexes, we based our analysis on a manually curated dataset from HPRD. In
      total, 1,060 complexes with 6,136 proteins from 2,187 unique genes were
      considered. We computed interologs in 25 different species and predicted the
      composition of complexes. Over the analysed species, the composition of most
      complexes was highly flexible and only 25% of all genes were never lost. Even if
      one component was lost at a particular point in time, the fraction of observed
      second, independent losses of additional components was high (75% of all
      complexes affected). Still, loss of whole complexes happened rarely. This
      biological signal deviated significantly from random models. We exemplified this
      trend on the anaphase promoting complex (APC) where a core is highly conserved
      throughout all metazoans, but flexibility in certain components is observable.
      CONCLUSION: Consecutive additions and losses of distinct units is a fundamental
      process in the evolution of protein complexes. These evolutionary events
      affecting genes coding for units in human protein complexes showed a
      significantly different phylogenetic pattern compared to randomly selected genes.
      Determination of taxon specific attachments or losses might be linked to specific
      cellular or morphological features. Thus, protein complexes contain not only
      structural and functional, but also evolutionary cores.

PMID- 19583844
TI  - Application of tri-colour, dual fusion fluorescence in situ hybridization (FISH)
      system for the characterization of BCR-ABL1 fusion in chronic myelogenous
      leukaemia (CML) and residual disease monitoring.
AB  - BACKGROUND: We studied the application of the BCR-ABL1 + 9q34 tri-colour dual
      fusion fluorescence in situ hybridization (FISH) system in the characterization
      of fusion signal pattern and the monitoring of residual disease in chronic
      myelogenous leukaemia (CML). The signal constellation on metaphases with the tri
      colour dual fusion system was defined. The knowledge of various signal patterns
      obtained from the different genetic rearrangements was further applied to the
      analysis of hybridization signals on interphase nuclei. METHODS: BCR-ABL1 dual
      colour, dual fusion FISH (D-FISH) was performed on diagnostic samples of 22 CML
      patients. The tri-colour FISH system was performed on cases that showed aberrant
      signal patterns other than the classical 1 green (G) 1 orange (O) 2 fusions (F).
      Using the aqua band-pass filter, random signal overlap in interphase nuclei would
      be indicated by the presence of an aqua signal (ASS1), while genuine fusion was
      represented by the absence of the ASS1 signal. RESULTS: Using the D-FISH system,
      the signal patterns could be categorized into 4 groups: group 1 (n = 17) showed
      the classical 1G1O2F; group 2 (n = 2) showed 2G1O1F indicating ABL1 deletion;
      group 3 (n = 1) showed 1G2O1F indicating BCR deletion; group 4 (n = 2) with
      1G1O1F indicating reciprocal ABL1-BCR deletion. The tri-colour dual fusion system
      correlated with the D-FISH system for cases with der(9) deletion. The added aqua
      labelled ASS1 probe was useful in differentiating random signal overlap from
      genuine BCR-ABL1 fusion in the interphase cells (group 4). CONCLUSION: Although
      the D-FISH probe was valuable in establishing the different patterns of aberrant
      signals and monitoring patients with the classic 2-fusion signals in CML, the tri
      colour dual fusion probe should be used for patients with der(9) deletion to
      monitor response to treatment.

PMID- 19583846
TI  - Nutrition induced pleomorphism and budding mode of reproduction in Deinococcus
      radiodurans.
AB  - BACKGROUND: Morphological adaptation is an important biological function of a
      microorganism to cope with its environment. Pleomorphism (to exist in a number of
      morphological forms) took centre stage in many discussions wherein a bacterium
      exhibits morphological transition and altered mode of reproduction in response to
      an environmental condition. FINDINGS: To strengthen the concept on pleomorphism
      in bacteria, we report here different cell morphologies of Deinococcus
      radiodurans in response to variation in nutrient concentration. From our studies
      we attempt primary evidence towards the presence of significant population of
      monomer cells of D. radiodurans in specific culture condition. In this report we
      also illustrate with scanning electron micrographs an unusual budding mode of
      reproduction in D. radiodurans which was not reported till date for this group of
      bacteria. CONCLUSION: In a holistic view the study reflects on bacterial shape
      (morphotypes) and the physiological adaptation to a particular nutrient
      environment. The discovery of budding mode of reproduction in Deinococcus will be
      of interest to microbiologists. It can serve as a model system to understand the
      mechanism of budding process at molecular level.

PMID- 19583845
TI  - Virological efficacy and emergence of drug resistance in adults on antiretroviral
      treatment in rural Tanzania.
AB  - BACKGROUND: Virological response to antiretroviral treatment (ART) in rural
      Africa is poorly described. We examined virological efficacy and emergence of
      drug resistance in adults receiving first-line ART for up to 4 years in rural
      Tanzania. METHODS: Haydom Lutheran Hospital has provided ART to HIV-infected
      patients since October 2003. A combination of stavudine or zidovudine with
      lamivudine and either nevirapine or efavirenz is the standard first-line regimen.
      Nested in a longitudinal cohort study of patients consecutively starting ART, we
      carried out a cross-sectional virological efficacy survey between November 2007
      and June 2008. HIV viral load was measured in all adults who had completed at
      least 6 months first-line ART, and genotypic resistance was determined in
      patients with viral load >1000 copies/mL. RESULTS: Virological response was
      measured in 212 patients, of whom 158 (74.5%) were women, and median age was 35
      years (interquartile range [IQR] 29-43). Median follow-up time was 22.3 months
      (IQR 14.0-29.9). Virological suppression, defined as <400 copies/mL, was observed
      in 187 patients (88.2%). Overall, prevalence of > or =1 clinically significant
      resistance mutation was 3.9, 8.4, 16.7 and 12.5% in patients receiving ART for 1,
      2, 3 and 4 years, respectively. Among those successfully genotyped, the most
      frequent mutations were M184I/V (64%), conferring resistance to lamivudine, and
      K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside
      reverse transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue
      mutations (TAMs), associated with cross-resistance to all nucleoside reverse
      transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both
      NRTIs and NNRTIs, was found in 64%. CONCLUSION: Virological suppression rates
      were good up to 4 years after initiating ART in a rural Tanzanian hospital.
      However, drug resistance increased with time, and dual-class resistance was
      common, raising concerns about exhaustion of future antiretroviral drug options.
      This study might provide a useful forecast of drug resistance and demand for
      second-line antiretroviral drugs in rural Africa in the coming years.

PMID- 19583847
TI  - BiGGEsTS: integrated environment for biclustering analysis of time series gene
      expression data.
AB  - BACKGROUND: The ability to monitor changes in expression patterns over time, and
      to observe the emergence of coherent temporal responses using expression time
      series, is critical to advance our understanding of complex biological processes.
      Biclustering has been recognized as an effective method for discovering local
      temporal expression patterns and unraveling potential regulatory mechanisms. The
      general biclustering problem is NP-hard. In the case of time series this problem
      is tractable, and efficient algorithms can be used. However, there is still a
      need for specialized applications able to take advantage of the temporal
      properties inherent to expression time series, both from a computational and a
      biological perspective. FINDINGS: BiGGEsTS makes available state-of-the-art
      biclustering algorithms for analyzing expression time series. Gene Ontology (GO)
      annotations are used to assess the biological relevance of the biclusters.
      Methods for preprocessing expression time series and post-processing results are
      also included. The analysis is additionally supported by a visualization module
      capable of displaying informative representations of the data, including
      heatmaps, dendrograms, expression charts and graphs of enriched GO terms.
      CONCLUSION: BiGGEsTS is a free open source graphical software tool for revealing
      local coexpression of genes in specific intervals of time, while integrating
      meaningful information on gene annotations. It is freely available at:
      http://kdbio.inesc-id.pt/software/biggests. We present a case study on the
      discovery of transcriptional regulatory modules in the response of Saccharomyces
      cerevisiae to heat stress.

PMID- 19583848
TI  - Limitation of using synthetic human odours to test mosquito repellents.
AB  - BACKGROUND: Gold-standard tests of mosquito repellents involve exposing human
      volunteers to host-seeking mosquitoes, to assess the protective efficacy of the
      repellents. These techniques are not exposure-free and cannot be performed prior
      to toxicological evaluation. It is postulated that synthetic lures could provide
      a useful assay that mimics in-vivo conditions for use in high-throughput
      screening for mosquito repellents. METHODS: This paper reports on a semi-field
      evaluation of repellents using a synthetic blend of human derived attractants for
      the malaria vector, Anopheles gambiae sensu stricto Different concentrations of
      known repellents, N, N diethyl-3-methylbenzamide (deet) and Para-methane-3, 8,
      diol (PMD) were added into traps baited with the synthetic blend, and resulting
      changes in mosquito catches were measured. RESULTS: All test concentrations of
      deet (0.001% to 100%) reduced the attractiveness of the synthetic blend. However,
      PMD was repellent only at 0.25%. Above this concentration, it significantly
      increased the attractiveness of the blend. There was no relationship between the
      repellent concentrations and the change in mosquito catches when either deet (r2
      = 0.033, P = 0.302) or PMD (r2 = 0.020, P = 0.578) was used. CONCLUSION: It is
      concluded that while some repellents may reduce the attractiveness of synthetic
      human odours, others may instead increase their attractiveness. Such
      inconsistencies indicate that even though the synthetic attractants may provide
      exposure-free and consistent test media for repellents, careful selection and
      multiple-repellent tests are necessary to ascertain their suitability for use in
      repellent screening. The synthetic odour blend tested here is not yet
      sufficiently refined to serve as replacement for humans in repellent testing, but
      may be developed further and evaluated in different formats for exposure free
      repellent testing purposes.

PMID- 19583849
TI  - Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian
      developmental stages in the female blue crab, Callinectes sapidus 2: novel
      specific binding sites in hepatopancreas and cAMP as a second messenger.
AB  - The finding that molt-inhibiting hormone (MIH) regulates vitellogenesis in the
      hepatopancreas of mature Callinectes sapidus females, raised the need for the
      characterization of its mode of action. Using classical radioligand binding
      assays, we located specific, saturable, and non-cooperative binding sites for MIH
      in the Y-organs of juveniles (J-YO) and in the hepatopancreas of vitellogenic
      adult females. MIH binding to the hepatopancreas membranes had an affinity 77
      times lower than that of juvenile YO membranes (KD values: 3.22 x 10(-8) and 4.19
      x 10(-10) M/mg protein, respectively). The number of maximum binding sites
      (B(MAX)) was approximately two times higher in the hepatopancreas than in the YO
      (B(MAX) values: 9.24 x 10(-9) and 4.8 x 10(-9) M/mg protein, respectively).
      Furthermore, MIH binding site number in the hepatopancreas was dependent on
      ovarian stage and was twice as high at stage 3 than at stages 2 and 1. SDS-PAGE
      separation of [125I] MIH or [125I] crustacean hyperglycemic hormone (CHH)
      crosslinked to the specific binding sites in the membranes of the J-YO and
      hepatopancreas suggests a molecular weight of approximately 51 kDa for a MIH
      receptor in both tissues and a molecular weight of approximately 61 kDa for a CHH
      receptor in the hepatopancreas. The use of an in vitro incubation of
      hepatopancreas fragments suggests that MIH probably utilizes cAMP as a second
      messenger in this tissue, as cAMP levels increased in response to MIH.
      Additionally, 8-Bromo-cAMP mimicked the effects of MIH on vitellogenin (VtG) mRNA
      and heterogeneous nuclear (hn) VtG RNA levels. The results imply that the
      functions of MIH in the regulation of molt and vitellogenesis are mediated
      through tissue specific receptors with different kinetics and signal
      transduction. MIH ability to regulate vitellogenesis is associated with the
      appearance of MIH specific membrane binding sites in the hepatopancreas upon
      pubertal/final molt.

PMID- 19583851
TI  - A randomized cross-over study of the quality of cardiopulmonary resuscitation
      among females performing 30:2 and hands-only cardiopulmonary resuscitation.
AB  - BACKGROUND: Hands-Only cardiopulmonary resuscitation (CPR) is recommended for use
      on adult victims of witnessed out-of-hospital (OOH) sudden cardiac arrest or in
      instances where rescuers cannot perform ventilations while maintaining minimally
      interrupted quality compressions. Promotion of Hands-Only CPR should improve the
      incidence of bystander CPR and, subsequently, survival from OOH cardiac arrest;
      but, little is known about a rescuer's ability to deliver continuous chest
      compressions of adequate rate and depth for periods typical of emergency services
      response time. This study evaluated chest compression rate and depth as subjects
      performed Hands-Only CPR for 10 minutes. For comparison purposes, each also
      performed chest compressions with ventilations (30:2) CPR. It also evaluated
      fatigue and changes in body biomechanics associated with each type of CPR.
      METHODS: Twenty healthy female volunteers certified in basic life support
      performed Hands-Only CPR and 30:2 CPR on a manikin. A mixed model repeated
      measures cross-over design evaluated chest compression rate and depth, changes in
      fatigue (chest compression force, perceived exertion, and blood lactate level),
      and changes in electromyography and joint kinetics and kinematics. RESULTS: All
      subjects completed 10 minutes of 30:2 CPR; but, only 17 completed 10 minutes of
      Hands-Only CPR. Rate, average depth, percentage at least 38 millimeters deep, and
      force of compressions were significantly lower in Hands-Only CPR than in 30:2
      CPR. Rates were maintained; but, compression depth and force declined
      significantly from beginning to end CPR with most decrement occurring in the
      first two minutes. Perceived effort and joint torque changes were significantly
      greater in Hands-Only CPR. Performance was not influenced by age. CONCLUSION:
      Hands-Only CPR required greater effort and was harder to sustain than 30:2 CPR.
      It is not known whether the observed greater decrement in chest compression depth
      associated with Hands-Only CPR would offset the potential physiological benefit
      of having fewer interruptions in compressions during an actual resuscitation. The
      dramatic decrease in compression depth in the first two minutes reinforces
      current recommendations that rescuers take turns performing compressions,
      switching every two minutes or less. Further study is recommended to determine
      the impact of real-time feedback and dispatcher coaching on rescuer performance.

PMID- 19583850
TI  - Postural changes in women with chronic pelvic pain: a case control study.
AB  - BACKGROUND: Chronic pelvic pain (CPP) is a lower abdominal pain lasting at least
      6 months, occurring continuously or intermittently and not associated exclusively
      with menstruation or intercourse. Although the musculoskeletal system has been
      found to be involved in CPP, few studies have assessed the contribution of
      posture in women with CPP. We aimed to determine if the frequency of postural
      changes was higher in women with CPP than healthy subjects. METHODS: A case
      control study included 108 women with CPP of more than 6 months' duration (CPP
      group) who consecutively attended at the Hospital of the University of Sao Paulo
      and 48 healthy female volunteers (control group). Postural assessment was
      noninvasive and performed in the standing position, with the reference points of
      Kendall used as normal parameters. Factors associated with CPP were assessed by
      logistic regression analysis. RESULTS: Logistic regression showed that the
      independent factors associated with CPP were postural changes in the cervical
      spine (OR 4.1; 95% CI 1.6-10.7; p < 0.01) and scapulae (OR 2.9; 95% CI 1.1-7.6; p
      < 0.05). CONCLUSION: Musculoskeletal changes were associated with CPP in 34% of
      women. These findings suggest that a more detailed assessment of women with CPP
      is necessary for better diagnosis and for more effective treatment.

PMID- 19583852
TI  - Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian
      developmental stages in the female blue crab, Callinectes sapidus 1: an ovarian
      stage dependent involvement.
AB  - To understand the hormonal coordination of the antagonism between molting and
      reproduction in crustaceans, the terminally anecdysial mature female Callinectes
      sapidus was used as a model. The regulatory roles of crustacean hyperglycemic
      hormone (CHH) and molt-inhibiting hormone (MIH) in vitellogenesis were examined.
      A competitive specific RIA was used to measure the levels of MIH and CHH in the
      hemolymphs of mature females at pre- and mid- vitellogenic stages, and their
      effects on vitellogenesis at early (early 2, E2) and mid vitellogenesis (3)
      stages were determined in vitro. A hepatopancreas fragments incubation system was
      developed and the levels of vitellogenin (VtG), as well as VtG mRNA and
      heterogeneous nuclear (hn)VtG RNA were determined using RIA or QPCR,
      respectively. MIH titers were four times higher at mid-vitellogenesis than at pre
      vitellogenesis, while CHH levels in the hemolymph were constant. In the in vitro
      incubation experiments, MIH increased both VtG mRNA levels and secretion at
      ovarian stage 3. At stage E2, however, MIH resulted in a mixed response:
      downregulation of VtG mRNA and upregulation of hnVtG RNA. CHH had no effect on
      any of the parameters. Actinomycin D blocked the stimulatory effects of MIH in
      stage 3 animals on VtG mRNA and VtG, while cycloheximide attenuated only VtG
      levels, confirming the MIH stimulatory effect at this stage. MIH is a key
      endocrine regulator in the coordination of molting and reproduction in the mature
      female C. sapidus, which simultaneously inhibits molt and stimulates
      vitellogenesis.

PMID- 19583853
TI  - A systematic investigation of the protein kinases involved in NMDA receptor
      dependent LTD: evidence for a role of GSK-3 but not other serine/threonine
      kinases.
AB  - BACKGROUND: The signalling mechanisms involved in the induction of N-methyl-D
      aspartate (NMDA) receptor-dependent long-term depression (LTD) in the hippocampus
      are poorly understood. Numerous studies have presented evidence both for and
      against a variety of second messengers systems being involved in LTD induction.
      Here we provide the first systematic investigation of the involvement of
      serine/threonine (ser/thr) protein kinases in NMDAR-LTD, using whole-cell
      recordings from CA1 pyramidal neurons. RESULTS: Using a panel of 23 inhibitors
      individually loaded into the recorded neurons, we can discount the involvement of
      at least 57 kinases, including PKA, PKC, CaMKII, p38 MAPK and DYRK1A. However, we
      have been able to confirm a role for the ser/thr protein kinase, glycogen
      synthase kinase 3 (GSK-3). CONCLUSION: The present study is the first to
      investigate the role of 58 ser/thr protein kinases in LTD in the same study. Of
      these 58 protein kinases, we have found evidence for the involvement of only one,
      GSK-3, in LTD.

PMID- 19583854
TI  - Identifying concerted evolution and gene conversion in mammalian gene pairs
      lasting over 100 million years.
AB  - BACKGROUND: Concerted evolution occurs in multigene families and is characterized
      by stretches of homogeneity and higher sequence similarity between paralogues
      than between orthologues. Here we identify human gene pairs that have undergone
      concerted evolution, caused by ongoing gene conversion, since at least the human
      mouse divergence. Our strategy involved the identification of duplicated genes
      with greater similarity within a species than between species. These genes were
      required to be present in multiple mammalian genomes, suggesting duplication
      early in mammalian divergence. To eliminate genes that have been conserved due to
      strong purifying selection, our analysis also required at least one intron to
      have retained high sequence similarity between paralogues. RESULTS: We identified
      three human gene pairs undergoing concerted evolution (BMP8A/B, DDX19A/B, and
      TUBG1/2). Phylogenetic investigations reveal that in each case the duplication
      appears to have occurred prior to eutherian mammalian radiation, with exactly two
      paralogues present in all examined species. This indicates that all three gene
      duplication events were established over 100 million years ago. CONCLUSION: The
      extended duration of concerted evolution in multiple distant lineages suggests
      that there has been prolonged homogenization of specific segments within these
      gene pairs. Although we speculate that selection for homogenization could have
      been utilized in order to maintain crucial homo- or hetero- binding domains, it
      remains unclear why gene conversion has persisted for such extended periods of
      time. Through these analyses, our results demonstrate additional examples of a
      process that plays a definite, although unspecified, role in molecular evolution.

PMID- 19583855
TI  - Social participation and independence in activities of daily living: a cross
      sectional study.
AB  - BACKGROUND: It is today widely accepted that participation in social activities
      contributes towards successful ageing whilst, at the same time, maintaining
      independence in the activities of daily living (ADLs) is the sine qua non for
      achieving that end. This study looks at people aged 65 and over living in an
      urban area in Spain who retain the ability to attend Social Centres providing
      recreational facilities. The aim of this paper is to quantify independence and
      identify the risk factors involved in its deterioration. METHODS: The sample size
      was calculated using the equation for proportions in finite populations based on
      a random proportional sample type, absolute error (e) = 0.05, alpha = 0.05, beta
      = 0.1, p = q = 0.5. Two-stage sampling was used. In the first place, the
      population was stratified by residence and a Social Centre was randomly chosen
      for each district. In the second stage, individuals were selected in a simple
      random sample without replacement in proportion to the number of members at each
      social centre.A multivariate logistical regression analysis takes functional ADL
      capacity as the dependent variable. The choice of predictive variables was made
      using a bivariate correlation matrix. Among the estimators obtained, Nagelkerke's
      R2 coefficient, and the Odds ratio (CI 95%) were considered. Sensitivity and 1
      specificity were adopted to present the results in graphic form. RESULTS: Out of
      this sample, 63.7% were fully capable of carrying out ADLs, while the main
      factors contributing to deterioration, identified on the basis of a logistic
      regression model, are in order of importance, poor physical health, poor mental
      health, age (above 75 years) and gender (female). The model employed has a
      predictive value of 88% and 92% (depending on the age range considered) with
      regard to the independence in ADLs. CONCLUSION: A review of the few Spanish works
      using similar methodology shows that the percentage of non-institutionalised
      persons who are independent enough to carry out ADLs is considerably lower than
      that found in this study of socially-active persons. Participation in
      recreational activities as part of a community may delay the onset of the
      dependence associated with ageing.

PMID- 19583856
TI  - Anti-malarial activity of 6-(8'Z-pentadecenyl)-salicylic acid from Viola websteri
      in mice.
AB  - BACKGROUND: Petroleum ether extracts of Viola websteri Hemsl (Violaceae) were
      reported to have anti-plasmodial activity against Plasmodium falciparum in vitro,
      with this activity being largely attributable to 6-(8'Z-pentadecenyl)-salicylic
      acid (6-SA). METHODS: The schizontocidal activity of 6-SA on early Plasmodium
      berghei infections was evaluated in a four-day test. The possible 'repository'
      activity of 6-SA was assessed using the method described by Peters. The median
      lethal dose (LD50) of 6-SA, when given intraperitoneally, was also determined
      using uninfected ICR mice and the method of Lorke. RESULTS: In the present study,
      6-SA was found to have anti-malarial activity in vivo, when tested against P.
      berghei in mice. 6-SA at 5, 10 and 25 mg/kg x day exhibited a significant blood
      schizontocidal activity in four-day early infections, repository evaluations and
      established infections with a significant mean survival time comparable to that
      of the standard drug, chloroquine (5 mg/kg.day). CONCLUSION: 6-SA possesses a
      moderate anti-malarial activity that could be exploited for malaria therapy.

PMID- 19583857
TI  - The feasibility of a single-blinded fast-track pragmatic randomised controlled
      trial of a complex intervention for breathlessness in advanced disease.
AB  - BACKGROUND: The Breathlessness Intervention Service is a novel service for
      patients with intractable breathlessness regardless of aetiology. It is being
      evaluated using the Medical Research Council's framework for the evaluation of
      complex interventions. This paper describes the feasibility results of Phase II:
      a single-blinded fast-track pragmatic randomised controlled trial. METHODS: A
      single-blinded fast-track pragmatic randomised controlled trial was conducted for
      patients with chronic obstructive pulmonary disease referred to the service.
      Patients were randomised to either receive the intervention immediately for an
      eight-week period, or receive the intervention after an eight-week period on a
      waiting list during which time they received standard care. Outcomes examined
      included: response rates to the trial; response rates to the individual
      questionnaires and items; comments relating to the trial functioning made during
      interviews with patients, carers, referrers and service providers; and,
      researcher fieldwork notes. RESULTS: 16 of the 20 eligible patients agreed to
      participate in a recruitment visit (16/20); 14 respondents went on to complete a
      recruitment visit/baseline interview. The majority of those who completed a
      recruitment visit/baseline interview completed the RCT protocol (13/14); 12 of
      their carers were recruited and completed the protocol. An unblinding rate of
      6/25 respondents (patients and carers) was identified. Missing data were minimal
      and only one patient was lost to follow up. The fast-track trial methodology
      proved feasible and acceptable. Two of the baseline/outcome measures proved
      unsuitable: the WHO performance scale and the Schedule for the Evaluation of
      Individual Quality of Life-Direct Weighting (SEIQoL-DW). CONCLUSION: This study
      adds to the evidence that fast-track randomised controlled trials are feasible
      and acceptable in evaluations of palliative care interventions for patients with
      non-malignant conditions. Reasonable response rates and low attrition rates were
      achieved. Further, with adequate preparation of the research and randomisation
      teams, clinicians, and responders, and effective liaison with the clinicians,
      single-blinding proved possible. Methods were identified to reduce unblinding
      through careful attention to the type of data collected at unblinded measurement
      points; the content of interviews should be carefully considered when designing
      blinded-trial protocols. TRIAL REGISTRATION: Clinical Trials.gov NCT00711438.

PMID- 19583858
TI  - Comparative chromosome mapping of repetitive sequences. Implications for genomic
      evolution in the fish, Hoplias malabaricus.
AB  - BACKGROUND: Seven karyomorphs of the fish, Hoplias malabaricus (A-G) were
      previously included in two major groups, Group I (A, B, C, D) and Group II (E, F,
      G), based on their similar karyotype structure. In this paper, karyomorphs from
      Group I were analyzed by means of distinct chromosomal markers, including silver
      stained nucleolar organizer regions (Ag-NORs) and chromosomal location of
      repetitive sequences (18S and 5S rDNA, and satellite 5SHindIII-DNA), through
      fluorescence in situ hybridization (FISH), in order to evaluate the evolutionary
      relationships among them. RESULTS: The results showed that several chromosomal
      markers had conserved location in the four karyomorphs. In addition, some other
      markers were only conserved in corresponding chromosomes of karyomorphs A-B and C
      D. These data therefore reinforced and confirmed the proposed grouping of
      karyomorphs A-D in Group I and highlight a closer relationship between
      karyomorphs A-B and C-D. Moreover, the mapping pattern of some markers on some
      autosomes and on the chromosomes of the XY and X1X2Y systems provided new
      evidence concerning the possible origin of the sex chromosomes. CONCLUSION: The
      in situ investigation of repetitive DNA sequences adds new informative characters
      useful in comparative genomics at chromosomal level and provides insights into
      the evolutionary relationships among Hoplias malabaricus karyomorphs.

PMID- 19583859
TI  - CD133 antigen expression in ovarian cancer.
AB  - BACKGROUND: Much attention has been recently focused on the role of cancer stem
      cells (CSCs) in the initiation and progression of solid malignancies. Since CSCs
      are able to proliferate and self-renew extensively, thus sustaining tumor growth,
      the identification of CSCs through their antigenic profile might have relevant
      clinical implications. In this context, CD133 antigen has proved to be a marker
      of tumor cells with stemness features in several human malignancies.The aim of
      the study was to investigate the clinical role of the immunohistochemically
      assessed expression of CD133 in a large single Institution series of ovarian
      cancer patients. METHODS: The study included 160 cases admitted to the
      Gynecologic Oncology Unit, Catholic University of Campobasso and Rome. CD133
      antigen was identified by the monoclonal mouse anti-CD133-1 antibody (clone CD133
      Miltenyi biotec). RESULTS: In the overall series CD133 positive tumor cells were
      observed in 50/160 (31.2%) cases. A diffuse cytoplasmic pattern was identified in
      30/50 (60.0%), while an apical cytoplasmic pattern was found in 20/50 (40.0%) of
      CD133 positive tumors.As of September 2008, the median follow up was 37 months
      (range: 2-112). During the follow up period, progression and death of disease
      were observed in 123 (76.9%), and 88 (55.0%) cases, respectively. There was no
      difference in TTP between cases with negative (median TTP = 23 months) versus
      positive CD133 expression (median TTP = 24 months) (p value = 0.3). Similar
      results were obtained for OS. When considering the TTP and OS curves according to
      the pattern of CD133 expression, a trend to a worse prognosis for cases with
      diffuse cytoplasmic versus the apical cytoplasmic pattern was documented,
      although the statistical significance was not reached. CONCLUSION: The
      immunohistochemical assessment of CD133 expression seems not to provide
      additional prognostic information in ovarian cancer patients. The role of the
      different pattern of CD133 immunoreaction deserves further investigation in a
      larger series.

PMID- 19583860
TI  - Discussing prognosis with older people with musculoskeletal pain: a cross
      sectional study in general practice.
AB  - BACKGROUND: Prognosis has been described as an important but neglected branch of
      clinical science. While patients' views have been sought in the context of life
      threatening illness, similar research is lacking for patients presenting with
      common, non-life-threatening musculoskeletal complaints. The aim of this study
      was to gauge whether and why older patients with musculoskeletal pain think
      prognostic information is important, and how often they felt prognosis was
      discussed in the general practice consultation. METHODS: A cross-sectional survey
      of consecutive patients aged 50 years of over presenting with non-inflammatory
      musculoskeletal pain to 5 Central Cheshire general practices. The frequency of
      responses to the prognostic questions were described and the association with
      sociodemographic, presenting pain complaint, and psychosocial variables explored
      using logistic regression. RESULTS: 502 participants (77%) responded to the
      postal questionnaire. 165 (33%) participants reported discussing prognosis in the
      consultation with their GP. Discussions about prognosis were more often reported
      by male patients (OR 1.72, 95% CI 1.09, 2.71) and those for whom this was their
      first consultation (OR 1.81, 95% CI 1.16, 2.80). 402 (82%) participants thought
      that prognostic information was important. This was highest among those currently
      in paid employment (OR 2.95, 95% CI 1.33, 6.57). The reasons patients gave for
      believing prognostic information was important included 'knowing for the sake of
      knowing' and planning future activity. Reasons for not believing prognostic
      information to be important included the belief that progression of pain was
      inevitable and that nothing could be done to help. CONCLUSION: Prognostic
      information is thought to be important amongst older people with musculoskeletal
      pain yet discussions occur infrequently in primary care. Barriers to effective
      prognostic communication and the exact information needs of patients are still
      unknown and warrant further research.

PMID- 19583861
TI  - Activation of estrogen receptor beta-dependent nitric oxide signaling mediates
      the hypotensive effects of estrogen in the rostral ventrolateral medulla of
      anesthetized rats.
AB  - BACKGROUND: Apart from their well-known peripheral cardiovascular effects,
      emerging evidence indicates that estrogen acts as a modulator in the brain to
      regulate cardiovascular functions. The underlying mechanisms of estrogen in
      central cardiovascular regulation, however, are poorly understood. The present
      study investigated the cardiovascular effects of 17beta-estradiol (E2beta) in the
      rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are
      located, and delineated the engagement of nitric oxide (NO) in E2beta-induced
      cardiovascular responses. METHODS: In male Sprague-Dawley rats maintained under
      propofol anesthesia, the changes of blood pressure, heart rate and sympathetic
      vasomotor tone after microinjection bilaterally into the RVLM of a synthetic
      estrogen, E2beta were examined for at least 120 min. The involvement of ERalpha
      and/or ERbeta subtypes was determined by microinjection of selective ERalpha or
      ERbeta agonist into bilateral RVLM. Different NO synthase (NOS) inhibitors were
      used to evaluate the involvement of differential of NOS isoforms in the
      cardiovascular effects of E2beta. RESULTS: Bilateral microinjection of E2beta
      (0.5, 1, or 5 pmol) into the RVLM dose-dependently decreased systemic arterial
      pressure (SAP) and the power density of the vasomotor components of SAP signals,
      our experimental index for sympathetic neurogenic vasomotor tone. These
      cardiovascular depressive effects of E2beta (1 pmol) were abolished by co
      injection of ER antagonist ICI 182780 (0.25 or 0.5 pmol), but not a transcription
      inhibitor actinomycin D (10 nmol). Like E2beta, microinjection bilaterally into
      the RVLM of a selective ERbeta agonist 2,3-bis(4-hydroxyphenyl) propionitrile
      (DPN, 1, 2, or 5 pmol) induced significant decreases in these hemodynamic
      parameters in a dose-dependent manner. In contrast, the selective ERalpha agonist
      1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (5 pmol) did not influence the
      same cardiovascular parameters. Co-administration bilaterally into the RVLM of
      NOS inhibitor NG-nitro-L-arginine methyl ester (5 nmol) or selective inducible
      NOS (iNOS) inhibitor S-methylisothiourea (25 pmol), but not selective neuronal
      NOS inhibitor 7-nitroindazole (0.5 pmol) or endothelial NOS inhibitor N5-(1
      Iminoethyl)-L-ornithine (2.5 pmol), significantly attenuated the cardiovascular
      depressive effects elicited by DPN (2 pmol). CONCLUSION: Our results indicate
      that E2beta in the RVLM elicited short-term cardiovascular depressive effects via
      an ERbeta-dependent nontranscriptional mechanism. These vasodepressor effects of
      E2beta are likely to be mediated by the iNOS-derived NO in the RVLM.

PMID- 19583862
TI  - Impact of housing on the survival of persons with AIDS.
AB  - BACKGROUND: Homeless persons with HIV/AIDS have greater morbidity and mortality,
      more hospitalizations, less use of antiretroviral therapy, and worse medication
      adherence than HIV-infected persons who are stably housed. We examined the effect
      of homelessness on the mortality of persons with AIDS and measured the effect of
      supportive housing on AIDS survival. METHODS: The San Francisco AIDS registry was
      used to identify homeless and housed persons who were diagnosed with AIDS between
      1996 and 2006. The registry was computer-matched with a housing database of
      homeless persons who received housing after their AIDS diagnosis. The Kaplan
      Meier product limit method was used to compare survival between persons who were
      homeless at AIDS diagnosis and those who were housed. Proportional hazards models
      were used to estimate the independent effects of homelessness and supportive
      housing on survival after AIDS diagnosis. RESULTS: Of the 6,558 AIDS cases, 9.8%
      were homeless at diagnosis. Sixty-seven percent of the persons who were homeless
      survived five years compared with 81% of those who were housed (p < 0.0001).
      Homelessness increased the risk of death (adjusted relative hazard [RH] 1.20; 95%
      confidence limits [CL] 1.03, 1.41). Homeless persons with AIDS who obtained
      supportive housing had a lower risk of death than those who did not (adjusted RH
      0.20; 95% CL 0.05, 0.81). CONCLUSION: Supportive housing ameliorates the negative
      effect of homelessness on survival with AIDS.

PMID- 19583865
TI  - DNA watermarks in non-coding regulatory sequences.
AB  - BACKGROUND: DNA watermarks can be applied to identify the unauthorized use of
      genetically modified organisms. It has been shown that coding regions can be used
      to encrypt information into living organisms by using the DNA-Crypt algorithm.
      Yet, if the sequence of interest presents a non-coding DNA sequence, either the
      function of a resulting functional RNA molecule or a regulatory sequence, such as
      a promoter, could be affected. For our studies we used the small cytoplasmic RNA
      1 in yeast and the lac promoter region of Escherichia coli. FINDINGS: The lac
      promoter was deactivated by the integrated watermark. In addition, the RNA
      molecules displayed altered configurations after introducing a watermark, but
      surprisingly were functionally intact, which has been verified by analyzing the
      growth characteristics of both wild type and watermarked scR1 transformed yeast
      cells. In a third approach we introduced a second overlapping watermark into the
      lac promoter, which did not affect the promoter activity. CONCLUSION: Even though
      the watermarked RNA and one of the watermarked promoters did not show any
      significant differences compared to the wild type RNA and wild type promoter
      region, respectively, it cannot be generalized that other RNA molecules or
      regulatory sequences behave accordingly. Therefore, we do not recommend
      integrating watermark sequences into regulatory regions.

PMID- 19583864
TI  - The relation between the incidence of hypernatremia and mortality in patients
      with severe traumatic brain injury.
AB  - INTRODUCTION: The study was aimed at verifying whether the occurrence of
      hypernatremia during the intensive care unit (ICU) stay increases the risk of
      death in patients with severe traumatic brain injury (TBI). We performed a
      retrospective study on a prospectively collected database including all patients
      consecutively admitted over a 3-year period with a diagnosis of TBI (post
      resuscitation Glasgow Coma Score < or = 8) to a general/neurotrauma ICU of a
      university hospital, providing critical care services in a catchment area of
      about 1,200,000 inhabitants. METHODS: Demographic, clinical, and ICU laboratory
      data were prospectively collected; serum sodium was assessed an average of three
      times per day. Hypernatremia was defined as two daily values of serum sodium
      above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox
      proportional-hazards regression models were used, with time-dependent variates
      designed to reflect exposure over time during the ICU stay: hypernatremia,
      desmopressin acetate (DDAVP) administration as a surrogate marker for the
      presence of central diabetes insipidus, and urinary output. The same models were
      adjusted for potential confounding factors. RESULTS: We included in the study 130
      TBI patients (mean age 52 years (standard deviation 23); males 74%; median
      Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50
      (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died
      within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the
      patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances
      hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The
      occurrence of hypernatremia was highest (P = 0.003) in patients with suspected
      central diabetes insipidus (25/130, 19.2%), a condition that was associated with
      increased severity of brain injury and ICU mortality. After adjustment for the
      baseline risk, the incidence of hypernatremia over the course of the ICU stay was
      significantly related with increased mortality (hazard ratio 3.00 (95% confidence
      interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P
      = 0.06), hypernatremia providing no additional prognostic information in the
      instances of suspected central diabetes insipidus. CONCLUSIONS: Mild
      hypernatremia is associated with an increased risk of death in patients with
      severe TBI. In a proportion of the patients the association between hypernatremia
      and death is accounted for by the presence of central diabetes insipidus.

PMID- 19583866
TI  - Total antioxidant capacity--a novel early bio-chemical marker of oxidative stress
      in HIV infected individuals.
AB  - BACKGROUND: Oxidative stress induced by the production of reactive oxygen species
      may play a critical role in the stimulation of HIV replication and the
      development of immunodeficiency. This study was conducted as there are limited
      and inconclusive studies on the significance of a novel early marker of oxidative
      stress which can reflect the total antioxidant capacity in HIV patients, METHODS:
      Total antioxidant capacity (TAC) and lipid peroxidation were evaluated in 50 HIV
      1 seropositive patients (including HIV-1 symptomatics and asymptomatics).
      Controls included 50 age and sex matched and apparently healthy HIV-1
      seronegative subjects. Serum malondialdehyde (MDA), Total antioxidant capacity
      [TAC] (by ferric reducing antioxidant power assay), vitamin E, vitamin C and
      superoxide dismutase (SOD) enzyme activity were estimated among controls and
      cases. Statistical comparisons and correlations at 5% level of significance were
      determined. RESULTS AND DISCUSSION: The mean MDA concentrations were
      significantly elevated in both HIV-1 asymptomatic (CD4+ count > 500
      cells/microliter) and HIV-1 symptomatic (CD4+ count <500 cells/microliter) groups
      (Mean +/- S.D values were 2.2 +/- 0.7 nmol/ml and 2.8 +/- 0.8 nmol/ml
      respectively) when compared with the control group (mean +/- S.D value was 0.9 +/
      0.2 nmol/ml) (p < 0.01). The mean TAC of HIV-1 asymptomatic and HIV-1
      symptomatic (Mean +/- S.D values were 754.6 +/- 135.6 micromol/L and 676.6 +/-
      154.1 micromol/L respectively) patients were significantly reduced compared with
      the control group (Mean +/- S.D value was 1018.7 +/- 125.6 micromol/L) (p <
      0.01). Also, there were significantly decreased levels of vitamin E, vitamin C
      and SOD among HIV-1 seropositive patients(controls > asymptomatic > symptomatic)
      compared to controls (p < 0.01). TAC showed significant negative correlation with
      MDA among HIV-1 infected patients (p < 0.01). CONCLUSION: Our results clearly
      show that severe oxidative stress occurs in the HIV-1 seropositive patients in
      comparison with controls, and increases significantly with the progression of
      disease, i.e. HIV-1 symptomatics > asymptomatics > controls. TAC can be used as a
      novel early bio-chemical marker of oxidative stress in HIV-1 infected patients
      which may result in reduced tissue damage by free radicals and help to monitor
      and optimize antioxidant therapy in such patients.

PMID- 19583867
TI  - Poverty, social exclusion and dental caries of 12-year-old children: a cross
      sectional study in Lima, Peru.
AB  - BACKGROUND: Socioeconomic differences in oral health have been reported in many
      countries. Poverty and social exclusion are two commonly used indicators of
      socioeconomic position in Latin America. The aim of this study was to explore the
      associations of poverty and social exclusion with dental caries experience in 12
      year-old children. METHODS: Ninety families, with a child aged 12 years, were
      selected from 11 underserved communities in Lima (Peru), using a two-stage
      cluster sampling. Head of households were interviewed with regard to indicators
      of poverty and social exclusion and their children were clinically examined for
      dental caries. The associations of poverty and social exclusion with dental
      caries prevalence were tested in binary logistic regression models. RESULTS:
      Among children in the sample, 84.5% lived in poor households and 30.0% in
      socially excluded families. Out of all the children, 83.3% had dental caries.
      Poverty and social exclusion were significantly associated with dental caries in
      the unadjusted models (p = 0.013 and 0.047 respectively). In the adjusted model,
      poverty remained significantly related to dental caries (p = 0.008), but the
      association between social exclusion and dental caries was no longer significant
      (p = 0.077). Children living in poor households were 2.25 times more likely to
      have dental caries (95% confidence interval: 1.24; 4.09), compared to those
      living in non-poor households. CONCLUSION: There was support for an association
      between poverty and dental caries, but not for an association between social
      exclusion and dental caries in these children. Some potential explanations for
      these findings are discussed.

PMID- 19583868
TI  - Intravenous fluid restriction after major abdominal surgery: a randomized blinded
      clinical trial.
AB  - BACKGROUND: Intravenous (IV) fluid administration is an essential part of
      postoperative care. Some studies suggest that a restricted post-operative fluid
      regime reduces complications and postoperative hospital stay after surgery. We
      investigated the effects of postoperative fluid restriction in surgical patients
      undergoing major abdominal surgery. METHODS: In a blinded randomized trial, 62
      patients (ASA I-III) undergoing elective major abdominal surgical procedures in a
      university hospital were allocated either to a restricted (1.5 L/24 h) or a
      standard postoperative IV fluid regime (2.5 L/24 h). Primary endpoint was length
      of postoperative hospital stay (PHS). Secondary endpoints included postoperative
      complications and time to restore gastric functions. RESULTS: After a 1-year
      inclusion period, an unplanned interim analysis was made because of many protocol
      violations due to patient deterioration. In the group with the restricted regime
      we found a significantly increased PHS (12.3 vs. 8.3 days; p = 0.049) and
      significantly more major complications: 12 in 30 (40%) vs. 5 in 32 (16%) patients
      (Absolute Risk Increase: 0.24 [95%CI: 0.03 to 0.46], i.e. a number needed to harm
      of 4 [95%CI: 2-33]). Therefore, the trial was stopped prematurely. Intention to
      treat analysis showed no differences in time to restore gastric functions between
      the groups. CONCLUSION: Restricted postoperative IV fluid management, as
      performed in this trial, in patients undergoing major abdominal surgery appears
      harmful as it is accompanied by an increased risk of major postoperative
      complications and a prolonged postoperative hospital stay. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN16719551.

PMID- 19583869
TI  - Co-morbidities of vertiginous diseases.
AB  - BACKGROUND: Co-morbidities of vertiginous diseases have so far not been
      investigated systematically. Thus, it is still unclear whether the different
      vertigo syndromes (e.g. benign paroxysmal positional vertigo (BPPV), Meniere's
      disease (MD), vestibular migraine and phobic vertigo (PPV)) have also different
      spectrums of co-morbidities. METHODS: All patients from a cohort of 131
      participants were surveyed using a standardised questionnaire about the co
      morbidities hypertension, diabetes mellitus, BMI (body mass index), migraine,
      other headache, and psychiatric diseases in general and the likelihood of a
      depression in particular. RESULTS: We noted hypertension in 29.0% of the cohort,
      diabetes mellitus in 6.1%, migraine in 8.4%, other headache in 32.1%, psychiatric
      diseases in 16.0%, overweight and obesity in 33.6% and 13.7% respectively, as
      well as a clinical indication for depression in 15.9%. CONCLUSION: In general, we
      did not detect an increased prevalence of the co-morbidities diabetes mellitus,
      arterial hypertension, migraine, other headache and obesity compared to the
      general population. There was an increased prevalence of psychiatric co-morbidity
      in patients with PPV, and the prevalence of hypertension was elevated in patients
      with MD.

PMID- 19583870
TI  - Improvement of a real-time RT-PCR assay for the detection of enterovirus RNA.
AB  - We describe an improvement of an earlier reported real-time RT-PCR assay for the
      detection of enterovirus RNA, based on the 5' exonuclease digestion of a dual
      labeled fluorogenic probe by Taq DNA polymerase. A different extraction method,
      real-time RT-PCR instrument and primer set were evaluated. Our data show that the
      optimized assay yields a higher sensitivity and reproducibility and resulted in a
      significant reduced hands-on time per sample.

PMID- 19583871
TI  - Automating approximate Bayesian computation by local linear regression.
AB  - BACKGROUND: In several biological contexts, parameter inference often relies on
      computationally-intensive techniques. "Approximate Bayesian Computation", or ABC,
      methods based on summary statistics have become increasingly popular. A
      particular flavor of ABC based on using a linear regression to approximate the
      posterior distribution of the parameters, conditional on the summary statistics,
      is computationally appealing, yet no standalone tool exists to automate the
      procedure. Here, I describe a program to implement the method. RESULTS: The
      software package ABCreg implements the local linear-regression approach to ABC.
      The advantages are: 1. The code is standalone, and fully-documented. 2. The
      program will automatically process multiple data sets, and create unique output
      files for each (which may be processed immediately in R), facilitating the
      testing of inference procedures on simulated data, or the analysis of multiple
      data sets. 3. The program implements two different transformation methods for the
      regression step. 4. Analysis options are controlled on the command line by the
      user, and the program is designed to output warnings for cases where the
      regression fails. 5. The program does not depend on any particular simulation
      machinery (coalescent, forward-time, etc.), and therefore is a general tool for
      processing the results from any simulation. 6. The code is open-source, and
      modular.Examples of applying the software to empirical data from Drosophila
      melanogaster, and testing the procedure on simulated data, are shown. CONCLUSION:
      In practice, the ABCreg simplifies implementing ABC based on local-linear
      regression.

PMID- 19583872
TI  - Preliminary investigation of plasma levels of sex hormones and human growth
      factor(s), and P300 latency as correlates to cognitive decline as a function of
      gender.
AB  - BACKGROUND: Aging is marked by declines in levels of many sex hormones and growth
      factors, as well as in cognitive function. The P300 event-related potential has
      been established as a predictor of cognitive decline. We decided to determine if
      this measure, as well as 2 standard tests of memory and attention, may be
      correlated with serum levels of sex hormones and growth factors, and if there are
      any generalizations that could be made based on these parameters and the aging
      process. FINDINGS: In this large clinically based preliminary study several sex
      stratified associations between hormone levels and cognition were observed,
      including (1) for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly
      associated negatively with prolonged P300 latency; (2) for males aged 30 to 49,
      the spearman correlation between prolonged P300 latency and low free testosterone
      was significant; (3) for males aged 60 to 69, there was a significant negative
      correlation between P300 latency and DHEA levels; (4) for females aged 50 to 59
      IGFBP-3 significantly associated negatively with prolonged P300 latency; (5) for
      females at all age periods, estrogen and progesterone were uncorrelated with P300
      latency; and (6) for females aged 40 to 69, there was significant negative
      correlation between DHEA levels and P300 latency. Moreover there were no
      statistically significant correlations between any hormone and Wechsler Memory
      Scale-III (WMS-111). However, in females, there was a significant positive
      correlation between estrogen levels and the number of Attention Deficit Disorder
      (ADD) complaints. CONCLUSION: Given certain caveats including confounding factors
      involving psychiatric and other chronic diseases as well as medications, the
      results may still have important value. If these results could be confirmed in a
      more rigorously controlled investigation, it may have important value in the
      diagnosis, prevention and treatment of cognitive impairments and decline.

PMID- 19583873
TI  - A novel virus that infecting hypovirulent strain XG36-1 of plant fungal pathogen
      Sclerotinia sclerotiorum.
AB  - BACKGROUND: Sclerotinia sclerotiorum is a notorious plant fungal pathogen which
      spreads across the world. Hypovirulence is a phenomenon where the virulence of
      fungal pathogens is decreased, even lost, due to mycovirus infection. The
      potential of hypoviruses for biological control of the chestnut blight fungus
      (Cryphonectria parasitica) has attracted much interest, and has led to discovery
      of new hypovirulent strains in other fungi. RESULTS: A hypovirulent strain,
      strain XG36-1, was isolated from a typical lesion on the stem of rapeseed
      (Brassica napus) caused by Sclerotinia sclerotiorum. Strain XG36-1 grew on PDA
      very slowly (average 2.5 +/- 0.1 mm/d) with sectoring, and developed abnormal
      colony morphology with few sclerotia. Unlike health strains (such as wildtype
      strain XG-13), it was unable to induce lesions on detached leaves of rapeseed.
      Sclerotia of strain XG36-1 produced apothecia rarely. A sexual progeny test
      showed that the phenotypes of all 104 sexual progeny were not different from
      wildtype strain XG-13 which shows normal phenotype of S. sclerotiorum, and
      protoplast regeneration tests showed that 25.5% of the regenerants of strain XG36
      1 were recovered fully. Furthermore, the hypovirulence and its associated traits
      could be transmitted to XG36-1A34R, a hygromycin-resistance gene labelled sexual
      progeny of strain XG36-1, by hyphal anastomosis. Transmission electron microscope
      (TEM) observation showed that the cytoplasm of strain XG36-1 was destroyed and
      granulated; the membranes of nuclei and mitochondria were disintegrated; and
      mitochondrial cristae were cavitated. Viral particles (about 40 nm) in hyphae of
      strain XG36-1, but not in its sexual progeny and wildtype strain XG-13, could be
      observed with TEM, and several virus-like particles were uniquely enveloped by
      single layer membrane in the cells of strain XG36-1. Furthermore, the viral
      particles could be co-transmitted with the hypovirulence traits through hyphal
      anastomosis. CONCLUSION: Hypovirulence and its associated traits of strain XG36-1
      could be mediated by a fungal virus. Currently, we could not know the
      characteristic of this virus, but it likely represent a new type of mycovirus in
      S. sclerotiorum, and possibly in fungi.

PMID- 19583874
TI  - Serum heavy metals and hemoglobin related compounds in Saudi Arabia firefighters.
AB  - BACKGROUND: Firefighters are frequently exposed to significant concentrations of
      hazardous materials including heavy metals, aldehydes, hydrogen chloride,
      dichlorofluoromethane and some particulates. Many of these materials have been
      implicated in the triggering of several diseases. The aim of the present study is
      to investigate the effect of fire smoke exposure on serum heavy metals and
      possible affection on iron functions compounds (total iron binding capacity,
      transferrin saturation percent, ferritin, unsaturated iron-binding capacity blood
      hemoglobin and carboxyhemoglobin,). SUBJECTS AND METHODS: Two groups of male
      firefighter volunteers were included; the first included 28 firefighters from
      Jeddah city, while the second included 21 firefighters from Yanbu city with an
      overall age rang of 20-48 years. An additional group of 23 male non-firefighters
      volunteered from both cities as normal control subjects. Blood samples were
      collected from all volunteer subjects and investigated for relevant parameters.
      RESULTS: The results obtained showed that there were no statistically significant
      changes in the levels of serum heavy metals in firefighters as compared to normal
      control subjects. Blood carboxyhemoglobin and serum ferritin were statistically
      increased in Jeddah firefighters, (p < 0.05 and p < 0.05 respectively) and Yanbu
      firefighters, (p < 0.005 and p < 0.001 respectively) as compared to normal
      control group while serum TIBC and UIBC were statistically decreased in Yanbu
      firefighters as compared to Jeddah firefighters, (p < 0.005 and p < 0.005
      respectively) and normal control group, (p < 0.005 and p < 0.01 respectively). On
      the other hand, serum transferrin saturation percent was elevated in only Yanbu
      firefighters, (p < 0.05) as compared to Jeddah firefighters. Besides, there was
      no statistically significant change in blood hemoglobin and serum iron on
      comparison between all studied groups. CONCLUSION: Such results might point to
      the need for more health protective and prophylactic measures to avoid such
      hazardous health effects (elevated Blood carboxyhemoglobin and serum ferritin and
      decreased serum TIBC and UIBC) that might endanger firefighters working under
      dangerous conditions. Firefighters must be under regular medical follow-up
      through standard timetabled medical laboratory investigations to allow for early
      detection of any serum biochemical or blood hematological changes.

PMID- 19583875
TI  - Investigating the effects of climatic variables and reservoir on the incidence of
      hemorrhagic fever with renal syndrome in Huludao City, China: a 17-year data
      analysis based on structure equation model.
AB  - BACKGROUND: HFRS is a serious public health problem in China and the study on
      HFRS is important in China for its large population. The present study aimed to
      explore the impact of climatic variables and reservoir on the incidence of HFRS
      in Huludao City, an epidemic focus of the disease in northeastern China. METHODS:
      Structure Equation Model (SEM), a statistical technique for testing and
      estimating causal relationships, was conducted based on climatic variables, virus
      carrying index among rodents, and incidence of HFRS in the city during the period
      1990 to 2006. The linear structural relationships (LISREL) software (Scientific
      Software International, Lincolnwood, IL) was used to fit SEMs. RESULTS:
      Temperature, precipitation, relative humidity and virus-carrying index among
      rodents have shown positive correlations with the monthly incidence of HFRS,
      while air pressure had a negative correlation with the incidence. The best-fit
      SEM model fitted well with the data-based correlation matrix, P value was more
      than 0.56, root mean square error of approximation (RMSEA) equaled to 0, goodness
      of-fit index (GFI) was more than 0.99. CONCLUSION: Climate and reservoirs have
      affected the incidence of HFRS in Huludao City, located in northeastern China.
      Climate affects HFRS incidence mainly through the effect on reservoir in the
      study area. HFRS prevention and control should give more consideration to rodent
      control and climate variations.

PMID- 19583876
TI  - Development of an automated speech recognition interface for Personal Emergency
      Response Systems.
AB  - BACKGROUND: Demands on long-term-care facilities are predicted to increase at an
      unprecedented rate as the baby boomer generation reaches retirement age. Aging-in
      place (i.e. aging at home) is the desire of most seniors and is also a good
      option to reduce the burden on an over-stretched long-term-care system. Personal
      Emergency Response Systems (PERSs) help enable older adults to age-in-place by
      providing them with immediate access to emergency assistance. Traditionally they
      operate with push-button activators that connect the occupant via speaker-phone
      to a live emergency call-centre operator. If occupants do not wear the push
      button or cannot access the button, then the system is useless in the event of a
      fall or emergency. Additionally, a false alarm or failure to check-in at a
      regular interval will trigger a connection to a live operator, which can be
      unwanted and intrusive to the occupant. This paper describes the development and
      testing of an automated, hands-free, dialogue-based PERS prototype. METHODS: The
      prototype system was built using a ceiling mounted microphone array, an open
      source automatic speech recognition engine, and a 'yes' and 'no' response dialog
      modelled after an existing call-centre protocol. Testing compared a single
      microphone versus a microphone array with nine adults in both noisy and quiet
      conditions. Dialogue testing was completed with four adults. RESULTS AND
      DISCUSSION: The microphone array demonstrated improvement over the single
      microphone. In all cases, dialog testing resulted in the system reaching the
      correct decision about the kind of assistance the user was requesting. Further
      testing is required with elderly voices and under different noise conditions to
      ensure the appropriateness of the technology. Future developments include
      integration of the system with an emergency detection method as well as
      communication enhancement using features such as barge-in capability. CONCLUSION:
      The use of an automated dialog-based PERS has the potential to provide users with
      more autonomy in decisions regarding their own health and more privacy in their
      own home.

PMID- 19583877
TI  - Clinical significance of 4 patients with chronic hepatitis B achieving HBsAg
      clearance by treated with pegylated interferon alpha-2a for less than 1 year: a
      short report.
AB  - We report 4 chinese patients with hepatitis B e antigen-positive chronic
      hepatitis B achieving clearance of HBsAg by using pegylated interferon alpha-2a
      for less than 1 year, to provide one clinical clue for the treatment of chronic
      hepatitis B.

PMID- 19583878
TI  - Dark chocolate or tomato extract for prehypertension: a randomised controlled
      trial.
AB  - BACKGROUND: Flavanol-rich chocolate and lycopene-rich tomato extract have
      attracted interest as potential alternative treatment options for hypertension, a
      known risk factor for cardiovascular morbidity and mortality. Treatment of
      prehypertension (SBP 120-139/DBP 80-89 mmHg) may forestall progression to
      hypertension. However, there has been only limited research into non
      pharmacological treatment options for prehypertension. We investigated the effect
      of dark chocolate or tomato extract on blood pressure, and their acceptability as
      an ongoing treatment option in a prehypertensive population. METHODS: Our trial
      consisted of two phases: a randomised controlled three-group-parallel trial over
      12 weeks (phase 1) followed by a crossover of the two active treatment arms over
      an additional 12-week period (phase 2). Group 1 received a 50 g daily dose of
      dark chocolate with 70% cocoa containing 750 mg polyphenols, group 2 were
      allocated one tomato extract capsule containing 15 mg lycopene per day, and group
      3 received one placebo capsule daily over 8 weeks followed by a 4-week washout
      period. In phase 2 the active treatment groups were crossed over to receive the
      alternative treatment. Median blood pressure, weight, and abdominal circumference
      were measured 4-weekly, and other characteristics including physical activity,
      general health, energy, mood, and acceptability of treatment were assessed by
      questionnaire at 0, 8 and 20 weeks. We analysed changes over time using a linear
      mixed model, and one time point differences using Kruskal-Wallis, Fisher's-Exact,
      or t-tests. RESULTS: Thirty-six prehypertensive healthy adult volunteers
      completed the 6-month trial. Blood pressure changes over time within groups and
      between groups were not significant and independent of treatment. Weight and
      other characteristics did not change significantly during the trial. However, a
      marked difference in acceptability between the two treatment forms (chocolate or
      capsule) was revealed (p < 0.0001). Half of the participants allocated to the
      chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20%
      considered it an unacceptable long-term treatment option, whereas all
      participants found it easy and acceptable to take a capsule each day for blood
      pressure. CONCLUSION: Our study did not find a blood pressure lowering effect of
      dark chocolate or tomato extract in a prehypertensive population. Practicability
      of chocolate as a long-term treatment option may be limited. TRIAL REGISTRATION:
      http://www.anzctr.org.au Identifier: ACTRN12609000047291.

PMID- 19583879
TI  - Precursors and diverse pathways to personality disorder in children and
      adolescents.

PMID- 19583881
TI  - The development of personality disorders: perspectives from normal personality
      development in childhood and adolescence.
AB  - The developmental pathways leading to personality disorders are poorly
      understood, but clues to these pathways come from recent research on personality
      disorders and normal personality development in childhood and adolescence. The
      first section of this paper reviews recent work on personality disorders in
      childhood and adolescence, and concludes that personality disorders in
      adolescence are already prevalent, moderately stable, and impairing. The second
      section draws on McAdams and Pals' personality model to offer a taxonomy of
      personality differences that can account for the known patterns of emerging
      personality pathology. This taxonomy includes youths' temperament and personality
      traits, mental representations (including attachment), coping strategies, and
      narrative identities. Individual differences in all of these domains may play
      critical roles in the development, manifestation, and course of personality
      disorders. Existing knowledge of normal and abnormal personality development can
      inform future research on the developmental pathways leading to personality
      pathology, the diagnostic criteria for personality disorders, and the development
      of validated treatments for personality disorders in the first two decades of
      life.

PMID- 19583880
TI  - A unifying perspective on personality pathology across the life span:
      developmental considerations for the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders.
AB  - Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-V) include replacing current personality disorder (PD)
      categories on Axis II with a taxonomy of dimensional maladaptive personality
      traits. Most of the work on dimensional models of personality pathology, and on
      personality disorders per se, has been conducted on young and middle-aged adult
      populations. Numerous questions remain regarding the applicability and
      limitations of applying various PD models to early and later life. In the present
      paper, we provide an overview of such dimensional models and review current
      proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing
      evidence on the development, measurement, and manifestation of personality
      pathology in early and later life focusing on those issues deemed most relevant
      for informing DSM-V. Finally, we present overall conclusions regarding the need
      to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight
      the advantages of a dimensional model in unifying PD perspectives across the life
      span.

PMID- 19583883
TI  - Childhood antecedents of personality disorder: an alternative perspective.
AB  - One of the fundamental limitations of the Diagnostic and Statistical Manual of
      Mental Disorders-Fourth Edition, Text Revision (DSM-IV-TR) categorical model of
      personality disorder classification has been the lack of a strong scientific
      foundation, including an understanding of childhood antecedents. The DSM-IV-TR
      personality disorders, however, do appear to be well understood as maladaptive
      variants of the domains and facets of the general personality structure as
      conceptualized within the five-factor model (FFM). Integrating the classification
      of personality disorder with the FFM brings to an understanding of the
      personality disorders a considerable body of scientific research on childhood
      antecedents. The temperaments and traits of childhood do appear to be antecedent
      to the FFM of adult personality structure, and these temperament and traits of
      childhood and adolescence are the likely antecedents for adult personality
      disorder, providing further support for the conceptualization of the adult
      personality disorders as maladaptive variants of the domains and facets of the
      FFM. Conceptualizing personality disorders in terms of the FFM thereby provides a
      basis for integrating the classification of abnormal and normal personality
      functioning across the life span.

PMID- 19583884
TI  - A structural-developmental psychodynamic approach to psychopathology: two
      polarities of experience across the life span.
AB  - Consistent with principles of developmental psychopathology, this paper presents
      a broad psychodynamic structural developmental perspective that establishes
      conceptual continuities between processes of normal personality development,
      personality organization, concepts of psychopathology, and processes of
      therapeutic change. The major assumption of this approach is that personality
      development proceeds in a dialectic synergistic interaction between the
      development of capacities for interpersonal relatedness and the development of
      self-definition or identity. Extensive research demonstrates that these two
      dimensions define two broad types of personality organization, each with a
      particular experiential mode; preferred forms of cognition, defense, and
      adaptation; unique qualities of interpersonal relatedness and specific types of
      object and self-representation. Severe disruptions of this normal dialectic
      developmental process result in various forms of psychopathology organized in two
      basic configurations in which there is distorted defensive preoccupation, at
      different developmental levels, with one of these polarities (relatedness or self
      definition) at the expense of the development of the other dimension. This paper
      reviews empirical findings supporting this approach to normal and disrupted
      personality development throughout the life cycle and considers its relationship
      to the internalizing-externalizing distinction in childhood and adolescence,
      attachment theory, and research on the interaction between biological and
      psychosocial factors in development across the life span. Finally, we discuss the
      implications of this approach for intervention and prevention.

PMID- 19583886
TI  - Adolescent attachment and trajectories of hostile-impulsive behavior:
      implications for the development of personality disorders.
AB  - Adolescents' trajectories of impulsive and hostile behaviors provide a dynamic
      index of risk for the emergence of Cluster B (antisocial and borderline)
      personality disorders in early adulthood. In the current study, we tested the
      hypothesis that preoccupied states of mind in the Adult Attachment Interview
      would increase both the level and rate of growth in adolescents' trajectories of
      aggressive and sexual risk-taking behaviors measured at ages 13, 15, and 17.
      Overall, preoccupied states of mind predicted higher levels of sexual risk taking
      and aggressive behaviors across all three assessments as well as higher rates of
      growth in sexual-risk taking and caregiver-reported aggression over time. In
      addition, preoccupied females showed slower rates of decline in self-reported
      hostile emotions than did preoccupied males. The effects of gender as a moderator
      of the relations between preoccupied status and risk trajectories for personality
      disorders are discussed.

PMID- 19583885
TI  - Predictors of withdrawal: possible precursors of avoidant personality disorder.
AB  - Relations of avoidant personality disorder (AvPD) with shyness and inhibition
      suggest that a precursor of AvPD is withdrawal. Using a sample of 4.5- to 7-year
      olds studied four times, 2 years apart, four and three classes of children
      differing in trajectories of mother- and teacher-reported withdrawal,
      respectively, were identified. Mothers and teachers generally did not agree on
      children's trajectories but the pattern of findings in the two contexts did not
      differ markedly. The mother-identified high and declining withdrawal class, in
      comparison with less withdrawn classes, and the teacher-identified high and
      declining class compared with low withdrawal classes, were associated with
      relatively high levels of anger and low levels of attentional control and
      resiliency. The mother-identified moderate and increasing withdrawal class was
      distinguished from less problematic withdrawal classes by higher anger, lower
      resiliency, and sometimes, lower attentional control. The teacher-identified low
      and increasing withdrawal class was distinguished from less problematic
      withdrawal classes by lower resiliency and lower attentional control. Findings
      are discussed in terms of the developmental precursors to social withdrawal and
      avoidant behavior.

PMID- 19583882
TI  - Multifinality in the development of personality disorders: a Biology x Sex x
      Environment interaction model of antisocial and borderline traits.
AB  - Although antisocial personality disorder (ASPD) is more common among males and
      borderline PD (BPD) is more common among females, some authors have suggested
      that the two disorders reflect multifinal outcomes of a single etiology. This
      assertion is based on several overlapping symptoms and features, including trait
      impulsivity, emotional lability, high rates of depression and suicide, and a high
      likelihood of childhood abuse and/or neglect. Furthermore, rates of ASPD are
      elevated in the first degree relatives of those with BPD, and concurrent
      comorbidity rates for the two disorders are high. In this article, we present a
      common model of antisocial and borderline personality development. We begin by
      reviewing issues and problems with diagnosing and studying PDs in children and
      adolescents. Next, we discuss dopaminergic and serotonergic mechanisms of trait
      impulsivity as predisposing vulnerabilities to ASPD and BPD. Finally, we extend
      shared risk models for ASPD and BPD by specifying genetic loci that may confer
      differential vulnerability to impulsive aggression and mood dysregulation among
      males and impulsive self-injury and mood dysregulation among females. Although
      the precise mechanisms of these sex-moderated genetic vulnerabilities remain
      poorly understood, they appear to interact with environmental risk factors
      including adverse rearing environments to potentiate the development of ASPD and
      BPD.

PMID- 19583887
TI  - Childhood personality pathology: dimensional stability and change.
AB  - Studies on the developmental course of personality disorders have suggested that
      adult personality disorders enclose both features with a natural plasticity over
      time, as well as stable components represented by underlying trait dimensions.
      The current study broadens this dimensional stability perspective toward an
      earlier developmental stage, and describes with different indices of stability
      the longitudinal behavior of basic childhood maladaptive trait dimensions in a
      community sample of 477 Flemish children. The results underscore structural, rank
      order, and within-person stability for the disagreeableness, emotional
      instability, introversion, and compulsivity dimensions and suggest a similar
      maturation principle as has been proposed for adults. Individual growth curve
      analyses indicate that children's maladaptive trait scores generally decrease as
      they grow older, with a smaller decline for high-scoring individuals. Childhood
      maladaptive traits and general psychopathology dimensions show similar
      longitudinal patterns in terms of shape and change over time, supporting a
      spectrum conceptualization of Axis I related pathology and personality disorder
      precursors at young age. The implications of these findings for a developmental
      perspective on dimensional conceptualizations of personality disorders are
      discussed.

PMID- 19583888
TI  - Conscientiousness and externalizing psychopathology: overlap, developmental
      patterns, and etiology of two related constructs.
AB  - The present paper focuses on the trait domain of conscientiousness, its
      development, and its relation to psychopathology. The definition of
      conscientiousness and its interface with specific forms of psychopathology, such
      as externalizing psychopathology, are discussed first. Then an overview of the
      known developmental changes in conscientiousness across the life course is
      provided, as well as the potential shared developmental etiology of
      conscientiousness and externalizing psychopathology. Given the lack of data,
      testing etiological factors that may contribute to the development of both
      conscientiousness and externalizing disorders, we report on three studies
      examining the childhood experiences associated with both conscientiousness and
      externalizing behaviors. Last, future directions are discussed.

PMID- 19583889
TI  - Child maltreatment and trajectories of personality and behavioral functioning:
      implications for the development of personality disorder.
AB  - This study investigated the longitudinal impact of maltreatment parameters on
      personality processes and maladjustment and prospective relationships between
      personality trajectory classes and subsequent maladjustment outcomes. The sample
      involved maltreated (n = 249) and nonmaltreated (n = 200) children followed
      longitudinally between ages 6 and 10. Growth mixture modeling indicated
      multifinality in personality development depending on the risk status (i.e.,
      maltreated vs. nonmaltreated). Two trajectory classes of ego resiliency were
      identified for maltreated children: those who showed a declining trajectory
      exhibited greater maladjustment. In contrast, three trajectory classes of ego
      control were identified for nonmaltreated children; the subgroups showing
      increases in ego undercontrol or dramatic changes from high ego undercontrol to
      high ego overcontrol exhibited poor adjustment. Experiencing multiple
      maltreatment subtypes and physical/sexual abuse were related to higher levels of
      ego undercontrol and externalizing symptomatology, whereas early onset of
      maltreatment was associated with the low and decreasing trajectory of ego
      resiliency and higher levels of internalizing symptomatology. The findings
      suggest that ego resiliency and ego control, personality processes related to
      self-regulation, may be important factors in identifying distinct pathways to
      later personality disorders as well as pathways to resilient functioning.

PMID- 19583890
TI  - Triarchic conceptualization of psychopathy: developmental origins of
      disinhibition, boldness, and meanness.
AB  - The clinical concept of psychopathy ("psychopathic personality") is generally
      considered to entail persistent behavioral deviancy in the company of emotional
      interpersonal detachment. However, longstanding debates continue regarding the
      appropriate scope and boundaries of the concept. Here, we review alternative
      historic descriptions of the disorder together with empirical findings for the
      best-established assessment instruments in use with adolescents and youth as a
      basis for formulating an integrative, triarchic model of psychopathy. The essence
      of the triarchic model is that psychopathy encompasses three distinct phenotypic
      constructs: disinhibition, which reflects a general propensity toward problems of
      impulse control; boldness, which is defined as the nexus of social dominance,
      emotional resiliency, and venturesomeness; and meanness, which is defined as
      aggressive resource seeking without regard for others ("dysaffliated agency").
      These differing phenotypic components are considered in terms of relevant
      etiologic and developmental pathways. The triarchic conceptualization provides a
      basis for reconciling and accommodating alternative descriptive accounts of
      psychopathy, and a framework for coordinating research on neurobiological and
      developmental processes contributing to varying manifestations of the disorder.

PMID- 19583891
TI  - Resting heart rate and the development of antisocial behavior from age 9 to 14:
      genetic and environmental influences.
AB  - The genetic and environmental basis of a well-replicated association between
      antisocial behavior (ASB) and resting heart rate was investigated in a
      longitudinal twin study, based on two measurements between the ages of 9 and 14
      years. ASB was defined as a broad continuum of externalizing behavior problems,
      assessed at each occasion through a composite measure based on parent ratings of
      trait aggression, delinquent behaviors, and psychopathic traits in their
      children. Parent ratings of ASB significantly decreased across age from childhood
      to early adolescence, although latent growth models indicated significant
      variation and twin similarity in the growth patterns, which were explained almost
      entirely by genetic influences. Resting heart rate at age 9-10 years old was
      inversely related to levels of ASB but not change patterns of ASB across age or
      occasions. Biometrical analyses indicated significant genetic influences on heart
      rate during childhood, as well as ASB throughout development from age 9 to 14.
      Both level and slope variation were significantly influenced by genetic factors.
      Of importance, the low resting heart rate and ASB association was significantly
      and entirely explained by their genetic covariation, although the heritable
      component of heart rate explained only a small portion (1-4%) of the substantial
      genetic variance in ASB. Although the effect size is small, children with low
      resting heart rate appear to be genetically predisposed toward externalizing
      behavior problems as early as age 9 years old.

PMID- 19583892
TI  - Neighborhoods and genes and everything in between: understanding adolescent
      aggression in social and biological contexts.
AB  - Adolescent aggression was explored in relation to neighborhood and genetic
      characteristics. Child saturation (the proportion of the population consisting of
      children under the age of 15), ethnic heterogeneity, poverty, and urbanicity of
      neighborhoods were examined in relation to adolescent aggression in 12,098
      adolescents followed longitudinally for 1 year. Longitudinal analyses indicated
      that child saturation was positively associated with increases in aggression,
      with this finding emerging among those living in the same neighborhood at both
      testing times and those who moved between testing times. In a subsample of males
      for whom genetic data were available, the relation of child saturation to
      adolescent aggression was moderated by the monoamine oxidase A (MAOA) gene. The
      regression of aggression on child saturation was steeper for those with the low
      activity version of the MAOA allele than among those with the high activity
      version of the allele. The implications of the results for an understanding of
      the origins and ontogeny of aggression and personality disorders are discussed.

PMID- 19583893
TI  - Types and continua in developmental psychopathology: problem behaviors in school
      and their relationship to later antisocial behavior.
AB  - In the study of developmental psychopathology a dimensional, variable-oriented
      approach dominates over a typological approach. With the person-oriented research
      paradigm providing the metatheoretical framework, pros and cons of these two
      approaches are discussed, and it is pointed to different methodological
      realizations of the typological approach, and to the contexts where they might be
      appropriate. It is also pointed out that the two important and underused concepts
      of equifinality and multifinality with advantage can be incorporated in a person
      oriented approach. An empirical example is given of the study of the structure of
      early adolescent problem behaviors and their relationship to later criminality
      where dimensional as well as typological analyses are carried out. The usefulness
      of the typological approach in studying the development and early manifestations
      of the personality disorder psychopathy is also discussed. It is concluded that
      the usefulness of a typological approach appears to be underestimated.

PMID- 19583895
TI  - Early maternal separation and the trajectory of borderline personality disorder
      symptoms.
AB  - Extended maternal separations before age 5 were evaluated as a predictor of long
      term risk for offspring borderline personality disorder (BPD) symptoms in
      longitudinal data from a large random community sample. Early separations from
      mother predicted elevations in BPD symptoms assessed repeatedly from early
      adolescence to middle adulthood. Early separations also predicted a slower than
      normal rate of decline in symptoms with age. Other theoretically grounded risks
      were examined and shown to predict elevated BPD symptoms over the developmental
      trajectory. Long-term effects of early separations were largely independent of
      childhood temperament, child abuse, maternal problems, and parenting risks. These
      data provide the first prospectively collected data on the developmental course
      of BPD symptoms and suggest a series of environmental and other influences on
      these very disabling problems.

PMID- 19583896
TI  - Using postgraduate students' evaluations of research experience to benchmark
      departments and faculties: issues and challenges.
AB  - BACKGROUND: The introduction of the Australian Research Training Scheme has been
      a strong reason for assuring the quality of the research higher degree (RHD)
      experience; if students experience poor supervision, an unsupportive climate, and
      inadequate infrastructure, prior research suggests RHD students will be less
      likely to complete their degree, with negative consequences for the student, the
      university, and society at large. AIMS: The present study examines the
      psychometric properties of a survey instrument, the Student Research Experience
      Questionnaire (SREQ), for measuring the RHD experience of currently enrolled
      students. The core scales of the SREQ focus on student experiences of
      Supervision; Infrastructure; Intellectual and Social Climate; and Generic Skills
      Development. SAMPLE: Participants were 2,213 postgraduate research students of a
      large, research-intensive Australian university. RESULTS: Preliminary factor
      analyses conducted at the student level supported the a priori four factors that
      the SREQ was designed to measure. However, multi-level analyses indicated that
      there was almost no differentiation between faculties or departments nested with
      faculties, suggesting that the SREQ responses are not appropriate for
      benchmarking faculties or departments. CONCLUSIONS: Consistent with earlier
      research based on comparisons across universities, the SREQ is shown to be almost
      completely unreliable in terms of benchmarking faculties or departments within a
      university.

PMID- 19583894
TI  - Representations of the caregiver-child relationship and of the self, and emotion
      regulation in the narratives of young children whose mothers have borderline
      personality disorder.
AB  - Borderline personality disorder (BPD) represents a severe distortion in the
      development of attachment, self, and emotion regulation. Study of children at
      high risk of developing BPD may inform precursors to BPD. In a low socioeconomic
      status sample of 30 children aged 4-7 whose mothers have BPD and 30 normative
      comparisons, representations of the caregiver-child relationship and of the self,
      and emotion regulation were assessed with a story-stem completion measure. In
      contrast to comparisons and controlling for major depressive disorder, children
      whose mothers have BPD told stories with the following: (a) more parent-child
      role reversal, more fear of abandonment, and more negative mother-child and
      father-child relationship expectations; (b) more incongruent and shameful
      representations of the self; and (c) poorer emotion regulation indicated by more
      confusion of boundaries between fantasy and reality and between self and fantasy,
      more fantasy proneness, less narrative coherence, and marginally more intrusion
      of traumatic themes. In the sample as a whole, (a) a maladaptive caregiver-child
      relationship composite was associated with maternal identity disturbance and self
      harm; (b) a maladaptive self-composite was associated with maternal self-harm;
      and (c) a maladaptive emotion regulation composite was associated with maternal
      identity disturbance, negative relationships, and self-harm. Results are
      discussed in terms of putative precursors to BPD and preventive interventions.

PMID- 19583897
TI  - Educational management: a neglected area.

PMID- 19583898
TI  - Workplace-based assessment (WPBA) portfolios in licensing for general practice
      specialty training.

PMID- 19583899
TI  - Developing a set of quality criteria for community-based medical education in the
      UK.
AB  - CONTEXT: General practices educate increasing numbers of learners at various
      stages. Criteria for educational provision exist, but practices supporting
      learners at different stages and from different institutions might face different
      criteria. METHODS: Criteria for practice-based teaching were developed at a
      workshop at a national conference. An online Delphi questionnaire invited
      educationalists to label these criteria as 'essential', 'desirable' or
      'unnecessary' for 'occasional', 'intensive' and 'foundation year' teaching. Two
      rounds of the Delphi were completed. The views about the criteria of a range of
      stakeholders were explored using focus groups and telephone interviews. RESULTS:
      We generated 76 criteria in five domains; physical environment, learning
      environment, tutor characteristics, patient involvement and departmental
      responsibilities. Stakeholders' views differed concerning the merits of criteria
      and which should take greatest priority. None felt that developing such a list
      was inappropriate. They proposed no new criteria to add to those identified in
      the Delphi process. CONCLUSION: To the best of our knowledge this is the first
      nationally derived list of criteria, capable of being used in both undergraduate
      and postgraduate practice-based medical education. These criteria can provide a
      benchmark against which to set local criteria.

PMID- 19583900
TI  - Exploring the perceptions of out-of-hours training for GP registrars in Wales.
AB  - This paper explores the perceptions of GP registrars about the quality of the
      training that they receive within out-of-hours (OOH) settings. Focus groups with
      trainers, clinical supervisors and GP registrars revealed three areas of
      interest: supervision, educational experience and system factors. Implications
      for OOH training are discussed.

PMID- 19583901
TI  - What's another year? A qualitative evaluation of extension of general practice
      training in the West of Ireland.
AB  - Vocational training in general practice has been shown to be effective in
      developing skilled, competent, independent practitioners. Nevertheless, many
      commentators have suggested that the traditional three-year training programme in
      the UK and Ireland does not prepare general practice registrars (GPRs) fully for
      independent practice and that extension of the general practice component of
      training would enhance capability development. This study describes the
      experience of one Irish training programme (the Western Area Training Programme
      in General Practice) during its transition from a three- to a four-year
      programme. METHODS: This study used focus group interviews to compare and
      contrast the expectations and experiences of three distinct groups: General
      practitioners (GPs) who completed the traditional three-year training programme
      and were interviewed after one year of independent practice. GPRs who were the
      first entrants into the new extended year of training who were interviewed at the
      beginning and at the end of the year. GP trainers who were the first trainers
      involved in the extended year of training who were also interviewed at the
      beginning and at the end of the year. RESULTS: The registrars who completed the
      extra year felt better prepared for independent practice than their counterparts
      who had completed the traditional shorter scheme, due mainly to an increased
      sense of professional confidence, a broader experience of different practice
      approaches, a greater knowledge of practice management and the additional career
      guidance received during their final year. Trainers and registrars described a
      different type of training relationship in the fourth year. The relationship
      could be described as more one of mentorship than a traditional trainer-trainee
      relationship. The customized design of the year provided an easier transition
      into independent practice than the sudden change experienced in the traditional
      programme but trainers felt that the flexibility offered could create unrealistic
      expectations of the reality of finding time for continued learning in general
      practice. Future research is suggested including followup studies of extended
      programmes to assess whether the apparent benefits detected in this study
      influence subsequent personal and practice development. It would also be valuable
      to explore the effects of the extended programme on the other stakeholders such
      as the programme directing team, the patients and other training practice team
      members.

PMID- 19583902
TI  - Extension of general practice training from three to four years: experiences of a
      vocational training programme in Southern Ireland.
AB  - The aim of this study was to evaluate the experiences of trainees taking part in
      an extended (four-year) general practice training programme introduced in the
      South Eastern region of the Republic of Ireland to replace the previous
      traditional (three-year) programme. In a qualitative design, eight homogeneous
      focus groups were held to determine the value of the additional year of training.
      The first cohort of trainees was interviewed towards the start and at the end of
      their fourth year. Trainees finishing the following year were also interviewed,
      as were graduates from the final three-year programme. GP trainers and the four
      members of the programme directing team comprised two further independent focus
      groups. Trainees reported that the integration of hospital posts and general
      practice attachments over the four years was particularly beneficial. The
      exposure to a variety of different general practices and the opportunity to take
      part in specialty clinics were considered extremely useful. The fourth year of
      training was felt to be less pressurised than previous years. Professional and
      personal development was enhanced; improved readiness to practise and confidence
      were noted. Perceived disadvantages of extended training included a lack of
      acknowledgment for doctors in their fourth year and excessive emphasis placed on
      research during the final year of training. The addition of an extra year of
      vocational training improves professional and personal development and changes
      the learning experience for doctors. Doctors felt more confident and ready to
      enter independent practice at the end of the fourth year of training.

PMID- 19583903
TI  - Short and long multiple-choice question stems in a primary care oriented
      undergraduate medical curriculum.
AB  - In this study Year 1 students in a new, primary care-oriented undergraduate
      course were offered a practice multiple-choice question (MCQ) examination with
      two question item formats--with and without brief primary care-based clinical
      scenarios--with the same correct answers. Data collected included: completion
      time; number correct; and responses to a questionnaire seeking student perception
      on the time required, clarity, ease of choice, and curriculum relevance. The mean
      scores for both groups of students were no different, although about 20% more
      time was required to complete clinical scenario stem question sets. Students
      perceived that the clinical scenarios had little effect on choosing the correct
      answer, improved question clarity and increased relevance to the curriculum. This
      study suggests that it is possible to assess junior medical students studying
      integrated undergraduate medical curricula by using MCQs containing brief
      clinical scenario stems, so long as either item numbers or timing are adjusted.
      This item format better reflects the learning process and may better prepare
      students for later professional practice assessment. GPs have an important role
      in developing assessment items that reflect early clinical integration.

PMID- 19583904
TI  - The assessment afternoon: an innovative way of doing workplace-based assessments
      for GP registrars.

PMID- 19583905
TI  - A teaching programme for general practice specialty trainees in ST2.

PMID- 19583906
TI  - Developing a new GP placement for medical students: the Shetland experience.

PMID- 19583907
TI  - Study effectively.
AB  - As a busy healthcare practitioner with a desire to maintain and update
      professional skills and knowledge, perhaps the study skills you acquired as an
      undergraduate may need to be updated and refined too. Issues of time management
      take on a different meaning with the increased pressures of juggling a busy
      career, home life and continuing professional development. As an undergraduate,
      your focus was very much on learning the volume of material that was delivered in
      the medical curriculum but was the idea of learning how to learn ever considered?
      This article is aimed at identifying some of the strategies that might be helpful
      in enabling you to make the most effective use of the time available to you for
      study and thereby ensuring that your learning opportunities are maximised.

PMID- 19583908
TI  - Recent advances in podoconiosis.
AB  - In terms of either research or public-health policy, podoconiosis, a non
      infectious form of elephantiasis, has received little attention since the 1980s.
      The aim of this narrative review is to examine the results of the relevant
      research published in the past 2 years, in the context of the data from earlier
      investigations. The review concludes by indicating areas in which further
      investigation is necessary before robust intervention strategies, to reduce the
      public-health burden posed by podoconiosis, can be devised.

PMID- 19583909
TI  - Blood banking in a malaria-endemic area: evaluating the problem posed by malarial
      parasitaemias.
AB  - The emergence and wide dissemination of drug-resistant malarial parasites
      underscore the need to prevent post-transfusion malaria. In Nigeria, as in most
      of sub-Saharan Africa, however, blood donors are not routinely screened for
      malarial infection. Recently, 391 consecutive potential blood donors in a malaria
      endemic area of south-western Nigeria were each checked for malarial parasitaemia
      using three methods: microscopy (all samples), OptiMAL (315 samples) and/or the
      Clinotech Malaria Cassette (142 samples). OptiMAL detects parasite-specific
      lactate dehydrogenase whereas the Clinotech test detects the surface proteins of
      merozoites and sporozoites. Microscopy revealed parasitaemias in 79 (20.2%) of
      the potential donors, the levels of parasitaemia varying from 34 to 6289 asexual
      parasites/microl (mean=445/microl). The prevalence of malarial parasitaemia, as
      detected by microscopy, was significantly higher during the rainy season than in
      the dry season (27.3% v. 5.5%; P<0.0001). There was no significant association
      between patent parasitaemia and fever (i.e. an axillary temperature > or =37.5
      degrees C), blood group, gender or anaemia. The corresponding prevalences of
      malarial parasitaemia detected using the rapid diagnostic tests were 3.8%
      (12/315) for OptiMAL and 57.8% (82/142) for the Clinotech. With the results of
      the microscopy used as the 'gold standard', OptiMAL gave a sensitivity of only
      16.0% but a specificity of 98.5%. The corresponding values for the Clinotech
      tests were 69.2% and 50.0%, respectively. It would clearly be beneficial to
      include screening for malaria parasitaemia in the routine investigation of
      potential blood donors in Nigeria, especially during the rainy season, when the
      risk of transfusion-transmitted malaria appears relatively high.

PMID- 19583910
TI  - Two recent but temporally distinct outbreaks of cutaneous leishmaniasis among
      foreign workers in the Dead-Sea area of Jordan.
AB  - Two temporally distinct outbreaks of human cutaneous leishmaniasis (CL), as well
      as scattered cases of the disease, have recently been observed close to the Dead
      Sea, in Jordan. Each of the two outbreaks, which occurred in 2004/2005 and
      2007/2008, involved a group of foreign workers who were deployed within otherwise
      uninhabited locations. During each outbreak, about 20% of the workers were found
      infected with the causative parasite. In the earlier outbreak, 61 workers were
      found to have skin lesions like those of CL and all but three were confirmed by
      culture and/or the examination of smears (40 cases) or, in the case of 18 (86%)
      of the 21 suspected cases found smear- and culture-negative, by PCR. In the
      second outbreak, the cases were only identified from their clinical
      manifestations and their response to antileishmanial treatment (cryotherapy).
      Leishmania major was identified as the cause of the 2004/2005 outbreak and some
      sporadic cases that occurred, in 2004, along the shores of the Dead Sea. The
      burrows of potential reservoir hosts were found close to the outbreak locations,
      frequently under the chenopod Seidlitzia rosmarinus. The two outbreaks emphasise
      the continuing problem posed by the CL focus in the Mid Jordan Valley and its
      impact on humans who move into the area. Curiously, an investigation on the socio
      economic conditions of the workers during the outbreaks identified a group of 48
      workers who were living in air-conditioned rooms during the 2007/2008 outbreak,
      among whom no CL cases were found. In contrast, 26 of a neighbouring group of 124
      workers, who were all living in non-air-conditioned rooms, developed CL lesions.
      The role of air conditioning, and of other factors and measures, in the
      prevention of the transmission of the causative parasites of CL merits further
      investigation and the attention of the local health authorities.

PMID- 19583911
TI  - Zoonotic tuberculosis and brucellosis in Africa: neglected zoonoses or minor
      public-health issues? The outcomes of a multi-disciplinary workshop.
AB  - Late in 2007, veterinary, medical and anthropological professionals from Europe
      and Africa met in a 2-day workshop in Pretoria, South Africa, to evaluate the
      burden, surveillance and control of zoonotic tuberculosis and brucellosis in sub
      Saharan Africa. Keynote presentations reviewed the burden of these diseases on
      human and livestock health, the existing diagnostic tools, and the available
      control methods. These presentations were followed by group discussions and the
      formulation of recommendations. The presence of Mycobacterium bovis and Brucella
      spp. in livestock was considered to be a serious threat to public health, since
      livestock and animal products are the only source of such infections in human
      beings. The impact of these pathogens on human health appears to be relatively
      marginal, however, when compared with Mycobacterium tuberculosis infections and
      drug resistance, HIV and malaria. Appropriate diagnostic tools are needed to
      improve the detection of M. bovis and Brucella spp. in humans. In livestock, the
      'test-and-slaughter' approach and the pasteurization of milk, which have been
      used successfully in industrialized countries, might not be the optimal control
      tools in Africa. Control strategies should fit the needs and perceptions of local
      communities. Improved intersectoral and international collaboration in
      surveillance, diagnosis and control, and in the education of medical and
      veterinary personnel, are advocated.

PMID- 19583912
TI  - Rickettsial infection in Amblyomma nodosum ticks (Acari: Ixodidae) from Brazil.
AB  - The rickettsial infections in 174 Amblyomma nodosum found on passeriform birds in
      the Atlantic forest, eastern Brazil, have recently been evaluated. Rickettsiae
      were successfully isolated from two ticks, using cultures of Vero cells. Both
      isolates were molecularly characterised, using the rickettsial genes gltA and
      htrA and, when possible, also ompA and ompB. Portions of the gltA and htrA genes
      from one of the rickettsial isolates were found be closely match the
      corresponding GenBank sequences for Rickettsia bellii, with 99.9% and 100%
      homology, respectively. This isolate was named R. bellii strain Pontal. Portions
      of the gltA, htrA and ompB genes from the second isolate most closely matched the
      corresponding sequences of R. parkeri, whereas a portion of the ompA gene from
      this isolate was closest to the relevant sequence of Rickettsia sp. strain
      COOPERI (which has been considered to be a strain of R. parkeri in Brazil). The
      second isolate was named R. parkeri strain NOD. Further investigation of the 172
      ticks from which isolates were not recovered revealed R. parkeri strain NOD in 40
      and R. bellii strain Pontal in nine, giving overall infection prevalences of
      23.6% (41/174) and 5.7% (10/174), respectively. This appears to be the first
      report of R. bellii and R. parkeri in A. nodosum.

PMID- 19583913
TI  - Crude extracts of, and purified compounds from, Pterocarpus angolensis, and the
      essential oil of Lippia javanica: their in-vitro cytotoxicities and activities
      against selected bacteria and Entamoeba histolytica.
AB  - In a recent study, various extracts of Pterocarpus angolensis were prepared and
      tested against bacteria. The acetone extract was found to be the most active
      against all the bacteria investigated, with minimum inhibitory concentrations
      varying from 0.0156 mg/ml against Staphylococcus aureus to 2 mg/ml against
      Enterobacter cloacae. Seven pure compounds were subsequently isolated from the
      ethanol extract of P. angolensis. Using several chromatographic and spectroscopic
      methods, the structures of five of these compounds - phthalate and four
      derivatives of epicatechin [(-)-epicatechin, epicatechin-3-O-galate, epicatechin
      (4beta-8)-epicatechin (B2), and a hexamer of epicatechin] - were successfully
      determined. The seven purified compounds were then further tested, in vitro,
      against Staphylococcus aureus and Entamoeba histolytica, and for their in-vitro
      cytotoxic activity. Although all seven were active against S. aureus, just one of
      the purified compounds from P. angolensis and piperitenone, a pure compound
      isolated from Lippia javanica essential oil, were found to have marked activity
      against Entamoeba histolytica, with median inhibitory concentrations (IC(50)) of
      25 and 100 microg/ml, respectively. The other P. angolensis compounds were either
      weakly active or showed no activity against the amoebae when tested at
      concentrations up to 400 microg/ml. All seven compounds isolated from P.
      angolensis showed less toxicity against cultures of human (HCT-8) cells than
      piperitenone, with IC(50) of 175-375 microg/ml. The presence of epichatechin and
      derivatives (with strong antibacterial activities but generally weak activities
      against Entamoeba histolytica) in the stem bark of P. angolensis has thus been
      demonstrated. Further investigation of the activities of these compounds and
      their potential use in the treatment of bacterial diseases appears justified.

PMID- 19583914
TI  - Health laboratories in the Tanga region of Tanzania: the quality of diagnostic
      services for malaria and other communicable diseases.
AB  - Although critical for good case management and the monitoring of health
      interventions, the health-laboratory services in sub-Saharan Africa are grossly
      compromised by poor infrastructures and a lack of trained personnel, essential
      reagents and other supplies. The availability and quality of diagnostic services
      in 37 health laboratories in three districts of the Tanga region of Tanzania have
      recently been assessed. The results of the survey, which involved interviews with
      health workers, observations and a documentary review, revealed that malaria
      accounted for >50% of admissions and out-patient visits. Most (92%) of the
      laboratories were carrying out malaria diagnosis and 89% were measuring
      haemoglobin concentrations but only one (3%) was conducting culture and
      sensitivity tests, and those only on urine and pus samples. Only 14 (17%) of the
      84 people found working in the visited laboratories were laboratory technologists
      with a diploma certificate or higher qualification. Sixteen (43%) of the study
      laboratories each had five or fewer types of equipment and only seven (19%) had
      more than 11 types each. Although 11 (30%) of the laboratories reported that they
      conducted internal quality control, none had standard operating procedures (SOP)
      on display or evidence of such quality assurance. Although malaria was the main
      health problem, diagnostic services for malaria and other diseases were
      inadequate and of poor quality because of the limited human resources, poor
      equipment and shortage of supplies. If the health services in Tanga are not to be
      overwhelmed by the progressively increasing burden of HIV/AIDS, malaria,
      tuberculosis and other emerging and re-emerging diseases, more funding and
      appropriate policies to improve the availability and quality of the area's
      diagnostic services will clearly be required.

PMID- 19583915
TI  - Successful use of miltefosine and sodium stibogluconate, in combination, for the
      treatment of an HIV-positive patient with visceral leishmaniasis: a case report
      and brief review of the literature.

PMID- 19583916
TI  - Use of multilocus microsatellite typing (MLMT) for the genetic analysis of Indian
      isolates of Leishmania donovani.

PMID- 19583917
TI  - A case of 'original antigenic sin' or just a paradoxical reaction in
      leptospirosis?

PMID- 19583928
TI  - Methodology of pharmacodynamic evaluation on Chinese herbal medicine based on
      syndrome differentiation.
AB  - The clinical application of Chinese herbal medicine should be based on syndrome
      differentiation in traditional Chinese medicine (TCM), and the pharmacological
      evaluation of herbal medicine in new drug discovery should be also based on the
      TCM syndrome differentiation. To clarify the Chinese herbal characteristics and
      mechanisms of action through pharmacological experiments is not only the
      inevitable requirement for Chinese herb modernization and internationalization,
      but also the key way to direct the clinical rational administration. Thus how to
      characterize the syndrome type in commonly used animal disease models becomes the
      key issue in pharmacological evaluation. Following the development of
      biomedicine, one important way to clarify the syndrome characteristics of animal
      disease model in the pharmacological evaluation is to compare the differences
      between the responsive and non-responsive animals, and to find out the
      responsiveness-related biocharacteristics. An important approach to set up the
      Chinese herbal pharmacological evaluation which is suitable for Chinese medicine
      differentiation is to utilize the method of surveying syndrome type with Chinese
      herb formula and select the responsive animal model to reflect certain syndrome
      type, and furthermore to clear up the syndrome characteristics of the animal
      model by investigating its modern biological basis and establishing the correct
      indications of special TCM syndrome type. This pharmacological evaluation way
      based on finding out the responsiveness-related biocharacteristics of herbal
      medicine could become more effective in evaluating drug effects, further
      improving the new drug discovery, and developing Chinese herbal medicine.

PMID- 19583929
TI  - [Evidence-based medicine and individualized health care].
AB  - In 21st century, clinical medicine moves toward a model of individualized health
      care. The development of the individualized model is based on the research
      findings of human genomics project including genotype and single nucleotide
      polymorphisms (SNPs), as well as the new health care model, that is, biological
      psychological-social-environmental-spiritual. It reflects the idea of patient
      centered care, and corresponds to the traditional practice of Chinese medicine,
      which addressed the individualized therapy on the basis of symptom pattern
      differentiation. However, the era of evidence-based medicine affords new meanings
      of individualized health care and promotes the research on the practice. The
      practice based on evidence would happen upon the integration of external research
      evidence, the expertise and experience of practitioners, and the value and
      preference of patients, so the decision of health care will be conscientious,
      explicit and judicious. This assay describes the meanings of individualized
      health care in different medical contexts, the characteristics of individualized
      practice in Chinese medicine, and proposals for further research in practice.

PMID- 19583930
TI  - [Effects of Songling Xuemaikang Capsule on ambulatory blood pressure in treatment
      of essential hypertension: a single-blind randomized controlled trial].
AB  - OBJECTIVE: To explore the effects of Western medicine including Ca(2+) channel
      antagonist and angiotensin-receptor antagonist combined with Songling Xuemaikang
      Capsule (SXC), a compound traditional Chinese herbal medicine for calming liver
      and suppressing liver yang, on blood pressure indexes derived from 24-hour
      ambulatory blood pressure monitoring (ABPM), and to evaluate the effects and
      stability of SXC in lowering blood pressure. METHODS: Seventy patients with
      essential hypertension of grade 2 or grade 3 were randomly assigned to routine
      group and SXC group. There were 35 cases in each group. The patients in the
      routine group were administered with 2.5 mg levoamlodipine and 40 mg telmisartan
      once daily, and 1.5 g SXC was administered orally to the patients in the SXC
      group three times daily besides levoamlodipine and telmisartan treatment. They
      were all treated for two weeks. Twenty-four-hour ABPM, trough to peak ratio and
      smoothness index were measured before and after the treatment. RESULTS: Twenty
      four-hour, day and night average systolic blood pressure (SBP) and 24-hour, day
      and night SBP load in the two groups were lowered as compared with before
      treatment (P < 0.05). The effects of Western medicine combined with SXC on blood
      pressure depression were better than those of Western medicine (P < 0.05).
      Western medicine combined with SXC had a significant influence on diastolic blood
      pressure (DBP) as compared with Western medicine (P < 0.05). The heart rate in
      the SXC group was reduced as compared with before treatment and the routine group
      (P < 0.05). Trough to peak ratio in SXC group was higher than that in the routine
      group, while there was no significant difference in smoothness index between the
      two groups. Morning surge in blood pressure in the two groups was improved as
      compared with before treatment (P < 0.05), and there was a significant difference
      in morning surge in blood pressure between the two groups (P < 0.05). CONCLUSION:
      Western medicine combined with SXC has long-lasting effects in lowering heart
      rate and blood pressure, especially for SBP and SBP load. SXC plus Western
      medicine also has an inhibition effect on morning surge in blood pressure.

PMID- 19583931
TI  - [Effects of Xuesaitong injection on coagulation function of gastric cancer
      patients undergoing laparoscopic surgery: a randomized controlled trial].
AB  - OBJECTIVE: To study the effects of Xuesaitong Injection, an extract from a
      Chinese herbal medicine, on coagulation function of gastric cancer patients
      undergoing laparoscopic surgery. METHODS: Fifty patients undergoing laparoscopic
      surgery for gastric cancer were randomly divided into control group and
      Xuesaitong group, with 25 patients in each group. Conventional anti-infection and
      transfusion treatment was given to the patients in the control group, and
      intravenous drip infusion of 400 mg Xuesaitong Injection added into 250 mL 5%
      glucose injection was administered once daily to the patients in the Xuesaitong
      group for 6 days from the first day after laparoscopic operation besides the
      conventional anti-infection and transfusion treatment. The values of prothrombin
      time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and
      international normalized ratio (INR) were detected by using blood coagulation
      method, and the values of D-dimer (D-D) before operation, instantly and 3, 5, 7
      days after operation were detected by using enzyme-linked immunosorbent assay in
      the two groups. Furthermore, the development of deep vein thrombosis on the day 7
      after operation was observed by vein angiography. RESULTS: There were no
      significant differences in the values of PT, APTT, INR, FIB and D-D between the
      two groups before operation, and there were no significant changes in APTT and
      INR after operation in the two groups. The values of PT decreased in the two
      groups on day 3 after operation, while there was no significant difference
      between the two groups. The value of PT in the control group decreased gradually
      with the extension of postoperation time (P < 0.05), while the PT value in the
      Xuesaitong group did not change significantly, and there was significant
      difference between the two groups (P < 0.05). The values of FIB and D-D increased
      instantly after operation in the two groups as compared with those before
      operation (P < 0.05), while there was no significant difference between the two
      groups. With the extension of postoperation time, the values of FIB and D-D
      increased gradually in the control group (P < 0.05); the D-D value on day 3 after
      operation increased, but the D-D values on day 5 and day 7 after operation
      decreased gradually in the Xuesaitong group (P < 0.05). The occurrence rate of
      deep vein thrombosis on day 7 after operation in the Xuesaitong group was lower
      than that in the control group. CONCLUSION: Laparoscopic surgery for gastric
      cancer may cause high agglutination condition, which will increase the risk of
      deep vein thrombosis, and Xuesaitong Injection can improve this state.

PMID- 19583932
TI  - [Color Doppler ultrasound evaluation of a Chinese herbal formula in treating
      lower limb arteriosclerosis: a randomized controlled trial].
AB  - OBJECTIVE: To observe the effects of a Chinese compound herbal medicine for
      reinforcing qi, activating blood circulation, expelling phlegm and dredging
      collaterals in treatment of lower limb arteriosclerosis. METHODS: The outpatients
      and inpatients with lower limb arteriosclerosis from Shanghai Yueyang Hospital of
      Integrated Traditional Chinese and Western Medicine were randomly divided into
      control group and treatment group after color Doppler ultrasound inspection, and
      there were 30 cases in each group. The patients in the treatment group were
      treated with simvastatin and a Chinese compound herbal medicine for reinforcing
      qi, activating blood circulation, expelling phlegm and dredging collaterals, and
      the patients in the control group were treated only with simvastatin. The color
      Doppler ultrasound imaging of lower limb arteries including inside diameter,
      intima-media thickness, and plaque area in all the patients were examined after 6
      month treatment. The levels of serum total cholesterol (TC) and low-density
      lipoprotein (LDL) were detected too. RESULTS: After the treatment, the lower limb
      artery intima-media thickness and artery plaque area in the treatment group
      decreased obviously as compared with those in the control group (P < 0.05). Color
      Doppler flow imaging showed that the percentage of patients with uniphase wave
      decreased from 26.67% (8/30) to 6.67% (2/30) in the treatment group (P < 0.05),
      and from 26.67% (8/30) to 16.67% (5/30) in the control group (P < 0.05) as
      compared with those before the treatment, and there was also a significant
      difference between the two groups (P < 0.05). The concentrations of serum TC and
      LDL in the treatment group were lower than those in the control group (P < 0.05).
      CONCLUSION: Color Doppler ultrasound showed that the Chinese compound medicine
      for reinforcing qi, activating blood circulation, expelling phlegm and dredging
      collaterals has positive effects on lower limb arteriosclerosis.

PMID- 19583933
TI  - [Distribution characteristics of common syndrome types and syndrome elements
      extracted by experts' experience in perimenopausal and postmenopausal women].
AB  - OBJECTIVE: To compare the distribution characteristics of common syndrome types
      and syndrome elements of menopause syndrome in perimenopausal and postmenopausal
      women on the basis of standardized syndrome differentiation extracted by experts'
      experiences. METHODS: A total of 1 582 outpatients with menopause syndrome who
      met with the diagnosis and inclusion criteria in seven grade 3 hospitals from
      October 2006 to June 2007 were included. A clinical epidemiological survey in the
      patients was carried out. The syndrome elements of disease location and
      characteristics were extracted and analyzed statistically by standardizing the
      syndrome differentiation of experts' experience in traditional Chinese medicine.
      RESULTS: There were 105 syndrome types after initial standardization, and the
      common syndrome types were kidney yin deficiency, deficiency of liver and kidney
      yin, stagnation of liver qi, and deficiency of both kidney yin and yang. Six
      syndrome elements of the disease location were extracted, among which the common
      elements were kidney, liver, spleen and heart. Seventeen syndrome elements of the
      disease characteristics were extracted, among which the common elements were yin
      deficiency, qi stagnation, qi deficiency, yang deficiency and deficiency.
      Syndrome types of stagnation of liver qi, deficiency of spleen and kidney, and qi
      stagnation were more frequently diagnosed during perimenopausal period, while the
      syndrome type of kidney yin deficiency was more frequently diagnosed during
      postmenopausal period, and the kidney was the main disease location. The
      distribution characteristics of the other syndrome types and elements were
      similar during the two periods. CONCLUSION: The syndrome type distribution in
      women with menopause syndrome is complex, while the syndrome element distribution
      is simple. Generally, the syndrome type and syndrome element distributions during
      perimenopausal and postmenopausal periods are similar, but there are significant
      differences in some syndrome types and syndrome elements between the two periods.
      All of these can give support for revealing the distribution rule of the common
      syndrome types and syndrome elements and give a theoretical basis for clinical
      treatment of menopause syndrome.

PMID- 19583934
TI  - [Functional brain magnetic resonance imaging in healthy people receiving
      acupuncture at Waiguan versus Waiguan plus Yanglingquan points: a randomized
      controlled trial].
AB  - OBJECTIVE: To observe the cerebral activating effects of needling at Waiguan
      (SJ5) versus SJ5 plus Yanglingquan (GB34) points in young healthy volunteers
      based on the hypothesis of "needling effect of combined acupuncture points
      relates to the brain activation". METHODS: Sixteen healthy volunteers were
      randomly divided into SJ5 group and SJ5 plus GB34 group, and there were 8
      volunteers in each group. The volunteers in the two groups received needling at
      corresponding points on the right hand or foot respectively. Nuclear magnetic
      resonance (1.5T, GE Corporation) was used for functional magnetic resonance
      imaging (fMRI) of the brain before and during the needling, and the obtained
      experimental data in the regional brain were processed and analyzed by the method
      of region of interest (ROI). RESULTS: The ROI activation induced by needling of
      SJ5 or SJ5 plus GB34 was all relatively concentrated (activation rate more than 4
      or activation point more than 10) on bilateral frontal and parietal lobes. There
      were no significant differences in ROI activation rates of brain regions between
      the two groups. ROI activation points showed that needling at SJ5 could activate
      the right cerebellum specifically (P < 0.05, vs SJ5 plus GB34), while needling at
      SJ5 plus GB34 could activate the left parietal and occipital lobes and bilateral
      basal ganglion more effectively than activate the other brain regions (P < 0.05,
      vs SJ5). ROI activation strength showed that needling at SJ5 plus GB34 could more
      strongly activate the right cerebellum (P < 0.05, vs SJ5). CONCLUSION: Based on
      fMRI data, a kind of acupuncture point combination of SJ5 and GB34 within the
      hand-foot Shaoyang meridians, could improve the motor and sensory dysfunctions
      and equilibrium disturbance. The effect of combined acupuncture points was proved
      by cerebral activity initially.

PMID- 19583935
TI  - Effects of Bushen Kangshuai Tang in retrieving oxidative stress-induced
      reproductive defects in Caenorhabditis elegans.
AB  - OBJECTIVE: To explore the function of Bushen Kangshuai Tang (BKT), a compound
      traditional Chinese herbal medicine, in alleviating oxidative stress-induced
      reproductive defects in organism nematode Caenorhabditis elegans. METHODS: The L4
      larvae were cultured with 25%, 50%, 75%, and 100% of BKT with the final
      concentration of 0.33 g/mL. Ultraviolet irradiation [20 J/(m(2) x min)], heat
      shock (36 degrees centigrade, 2 h), and paraquat treatment (2 mmol/L, 2h) were
      exerted as the stresses. Reproduction was assayed by the egg number in uterus,
      brood size, and generation time. RESULTS: Ultraviolet irradiation, heat-shock,
      and paraquat treatment could significantly reduce egg number in uterus and brood
      size, increase generation time, and suppress activities of catalase and
      superoxide dismutase of the treated wild-type N2 nematodes. Administration of BKT
      did not cause toxic or altered effects on reproduction under wild-type background
      in C. elegans. However, BKT administration at higher concentrations could not
      only effectively alleviate the reproductive defects induced by ultraviolet
      irradiation, heat-shock, and paraquat treatment, but also increase the catalase
      and superoxide dismutase activities suppressed by ultraviolet irradiation, heat
      shock, and paraquat treatment as compared with the control. Moreover,
      administration of BKT at higher concentrations could largely recover the
      reproductive defects formed in mev-1 mutant nematodes with elevated oxidative
      stress. CONCLUSION: Oxidative stress can negatively regulate the reproductive
      process, and the administration of high concentrations of BKT will largely
      retrieve the oxidative stress-induced reproductive defects in exposed nematodes.

PMID- 19583936
TI  - [Anti-inflammatory effects and quantitative study of the combinations of active
      ingredients of Painong powder in mice].
AB  - OBJECTIVE: To study the anti-inflammatory effects of the combinations of active
      components of Painong powder, a compound traditional Chinese herbal medicine, and
      the quantitative analysis of their interactions. METHODS: The mouse model of
      acute inflammation with increase of capillary permeability was induced by
      intraperitoneal injection of acetic acid. An orthogonal design with 2 levels
      (used and unused) was applied to assign the combinations groups of active
      ingredients including naringin and neohesperidin, peoniflorin, and platycodin.
      Aspirin and normal saline were administered as control. The pharmacodynamic
      interactions were analyzed by the optical density (OD) of infiltrated Evans blue.
      RESULTS: The different combinations of active ingredients showed anti
      inflammatory effect with different degree, and the predicted values of OD varied
      from 0.115 to 0.170. The maximum anti-inflammatory effect was from the
      combination of naringin, neohesperidin, paeoniflorin and platycodin, better than
      that of the saline group (P < 0.01). However, there was no significant difference
      as compared with the aspirin group (P > 0.05). Paeoniflorin showed a dominant
      contribution to the formula, and platycodin the least. The combination of all
      active components exhibited synergism. CONCLUSION: The results suggest that all
      the ingredients are efficacious constituents of the formula, and paeoniflorin
      shows a dominant contribution to the formula. More information about prescription
      compatibility can be obtained by the orthogonal simulation method.

PMID- 19583937
TI  - [Effects of Qushi Huayu Decoction in prevention and treatment of fatty liver in
      rats based on adiponectin-free fatty acid pathway].
AB  - OBJECTIVE: To explore the effects of Qushi Huayu Decoction (QSHYD), a compound
      traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic
      fatty liver disease (NAFLD) in rats. METHODS: Forty Wistar male rats were used to
      establish the NAFLD model by subcutaneous injection of carbon tetrachloride
      (CCl(4)) for 4 weeks (twice weekly) along with high-fat and low-protein diet for
      2 weeks. After two-week administration, the rats were randomly divided into four
      groups: untreated group, high-dose QSHYD group, medium-dose QSHYD group and low
      dose QSHYD group. Another six rats were used as normal control. After 2-week
      treatment, the following indexes were detected: (1) liver pathology; (2) contents
      of serum adiponectin (ADP) and liver triglyceride (TG); (3) concentrations of
      liver FFA, adiponectin receptor 2 (AdipoR2), malonyl-coenzyme A (malony1-CoA),
      AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACCase), fatty acid
      synthase (FAS) and carnitine palmitoyl transferase-1 (CPT-1). RESULTS: Compared
      with the normal group, there were physiological changes associated with hepatic
      steatosis and inflammation in liver tissues in the untreated group as observed by
      oil red O staining and HE staining. The TG, FFA, malony1-CoA, FAS, and ACCase
      concentrations in liver tissues in the untreated group were elevated
      significantly. While the contents of ADP in serum and AdipoR2, CPT-1 and AMPK in
      liver tissues in the untreated group were decreased markedly. The pathological
      damages in each QSHYD-treated group were significantly less than those in the
      untreated group. The TG and FFA contents in liver tissues in each QSHYD-treated
      group were significantly decreased. The FAS, ACCase and malonyl-CoA
      concentrations in liver tissues of the high QSHYD-treated group were reduced
      markedly as compared with the untreated group. High- and medium-dose of QSHYD
      could significantly increase ADP content in serum and AMPK, CPT-1 and AdipoR2
      contents in liver tissues. CONCLUSION: QSHYD can affect the ADP-FFA pathway by
      increasing the content of serum ADP, which may be one of its important mechanisms
      in preventing and treating NAFLD in rats.

PMID- 19583938
TI  - [Effects of Liangxue Jiedu Decoction in treating psoriasis in a mouse psoriasis
      model].
AB  - OBJECTIVE: To study the effects of Liangxue Jiedu Decoction, a compound
      traditional Chinese herbal medicine with the function of blood-cooling and
      detoxicating, in treating psoriasis in mice and to explore its mechanism.
      METHODS: (1) Sixty mice were randomly divided into Liangxue Jiedu Decoction
      group, compound Indigo Naturalis capsule group, acitretin capsule group and
      normal saline group. Another 10 mice were selected as blank control. After 2-week
      administration, mice were sacrificed to obtain samples. After hematoxylin and
      eosin (HE) staining, tail scales with granular layers were calculated by an
      optical microscope. (2) Except for ten mice in blank group, sixty female mice
      were injected intraperitoneally with diethylstilbestrol once daily. After 3-day
      injection, mice were randomly divided into four groups and treated as above
      description. After 2-week treatment, all mice were injected intraperitoneally
      with colchicine (2 mg/kg), and sacrificed 6 h after the injection. The mitotic
      rate in virginal epithelium was calculated after HE staining. RESULTS: Compared
      with normal saline, Liangxue Jiedu Decoction could significantly inhibit the
      mitosis of mouse vaginal epithelium (P < 0.01) and promote the formation of
      granular layers in mouse tail-scale epidermis (P < 0.01). CONCLUSION: The
      mechanism of Liangxue Jiedu Decoction in treating psoriasis may be related to
      promoting granular cell growth and inhibiting proliferation of epidermic cells.

PMID- 19583939
TI  - [Protective effect of catechin on renal microvessels in 5/6 nephrectomized rats
      and its mechanism].
AB  - OBJECTIVE: To investigate the effects of catechin on angiotensin-converting
      enzyme (ACE) activity, angiotensin II(Ang II) content and microvessel density
      (MVD) in renal tissues of 5/6 nephrectomized rats. METHODS: Sixty SD rats were
      divided into 3 groups: sham-operated group, untreated group and catechin group.
      Animal model was reproduced by 5/6 nephrectomy. After 8- and 12-week
      administration, rats were sacrificed. Renal MVD was measured by
      immunohistochemical method with CD34 marking. Activities of ACE in plasma and
      renal cortices were measured by ultraviolet spectrophotometer, and Ang II
      contents in plasma and renal cortices were measured by radioimmunoassay.
      Glomerular sclerosis index (GSI) and tubule interstitial score (TIS) were
      calculated by semiquantitative integration with hematoxylin and eosin staining
      and periodic acid-Schiff staining. RESULTS: After 8- and 12-week administration,
      the GSI and TIS in the catechin group were much less than those in the untreated
      group (P < 0.05, P < 0.01). MVDs around glomerulus and tubule at the end of the
      8th and 12th week in the untreated group and the catechin group were much less
      than those in the sham-operated group (P < 0.01). The ACE activities and Ang II
      contents in plasma and renal cortices in the catechin group were much less than
      those in the untreated group (P < 0.01). By Pearson correlation analysis, we
      found that MVD had negative correlation with GSI, TIS, Ang II content, and ACE
      activity (P < 0.01), however, the ACE activity and Ang II content had positive
      correlation with GSI, TIS (P < 0.01). CONCLUSION: Catechin can prevent the 5/6
      nephrectomized rats from decreasing of MVD and inhibit the progress of glomerular
      sclerosis and interstitial fibrosis by inhibiting the activity of ACE and
      reducing the production of Ang II.

PMID- 19583940
TI  - [Effects of electro-acupuncture on signal transduction pathway of hypothalamic
      neuroendocrine system in ovariectomized rats].
AB  - OBJECTIVE: To compare the varieties and contents of the main nerval information
      molecules in perfusate from hypothalamic medial preoptic area (MPOA) of the rats
      in different sexual cycles and the ovariectomized rats treated by electro
      acupuncture, so as to observe the similarities and differences of hypothalamic
      neuroendocrine signal transduction pathway under the physiological and
      pathological status, and to explore the mechanisms of neuroendocrine signal
      transduction of electro-acupuncture therapeutic effect in perimenopausal
      syndrome. METHODS: The stereo localization technique and push-and-pull perfusion
      of the rat brain nucleus were adopted for collecting the hypothalamic MPOA
      perfusate of the female rats with normal sexual cycle, and also for collecting
      the MPOA perfusate of ovariectomized rats after electro-acupuncture treatment as
      acupuncture perfusate (AP). After being respectively microinjected into MPOA of
      the ovariectomized rats, the influence of the different perfusates on vagina
      cytology and serum estradiol (E2) level was observed. The contents of
      gonadotropin-releasing hormone (GnRH), dopamine (DA), gamma-aminobutyric acid
      (GABA), glutamate (Glu), aspartate (Asp) and beta-endorphin (beta-EP) in the
      perfusate of each group were detected by radioimmunoassay or high performance
      liquid chromatography, and then the varieties and contents of these substances in
      the perfusate of each group were compared and analyzed. RESULTS: The contents of
      neural active substances including DA, GABA, Glu, and beta-EP in the perfusate
      from the rats' MPOA during different stages of sexual cycle showed some regular
      changes. After the perfusate was microinjected respectively into the MPOA of the
      ovariectomized rats, the changes of animal vaginal exfoliated cells and serum E2
      level showed the similar four-stage cycle characteristics as normal rats; the
      changes of vaginal exfoliated cells and serum E2 level of the ovariectomized rats
      without electro-acupuncture treatment showed the acupuncture-like effects
      following the microinjection of AP in the MPOA. CONCLUSION: The information
      molecules in the perfusate from MPOA of rats in normal sexual cycle or electro
      acupuncture-treated rats include classical neurotransmitters, amino acid
      neurotransmitters, and neuropeptides. Acupuncture may modulate the release and
      synthesis of these information molecules to normalize the subnormal function of
      MPOA in perimenopausal period. Thus, AP may be a neuroendocrine signal carrier of
      acupuncture effects for acupuncture signal transduction from one individual to
      another. This may provide a new thinking and method for studying acupuncture
      signal transduction of the acupuncture therapeutic effects on perimenopausal
      syndrome.

PMID- 19583941
TI  - [A review for a traditional Chinese medical journal Shou Shi Yi Bao].
AB  - Shou Shi Yi Bao was a journal of traditional Chinese medicine (TCM) during the
      period from 1935 to 1937, and was originated by Chen Huan-yun, a TCM physician in
      Suzhou. It is mainly to transmit the knowledge of TCM and to promote the epidemic
      prevention capacity of local public. The editorial characteristics and historical
      value of the journal were explored in initial background, staff writers,
      editorial policies, contents and the Editor Chen's medical ideas. Shou Shi Yi Bao
      was supported by many famous TCM physicians, although the journal was originated
      from the civil society. It was an academic TCM journal with perfect
      practicability for orientating to the public and highlighting the academic
      spirit. Chen Huan-yun was a resolute defender of TCM, and had many opinions on
      clinical practice and lots of scientific suggestions on TCM development. Shou Shi
      Yi Bao reflected the main characteristics of TCM journals in 1930s. The journal
      was one of the important documents to study the TCM history during the period of
      the Republic of China in Jiangsu Province, and it also set a stage for the
      struggle between TCM and Western medicine at that time. The documentary
      information of the journal has literature and history values in reflecting the
      historical process of TCM self-improvement. The success of the journal was due to
      not only the broken-up sectarian bias and cooperation of the TCM practitioners
      but also the preponderant geographic and cultural circumstances of Suzhou as well
      as Chen Huan-yun's profound knowledge in traditional Chinese culture and
      medicine.

PMID- 19583942
TI  - Research on receptors related to acupuncture analgesia and positron emission
      tomography radioligands: a review.

PMID- 19583943
TI  - [How to express quantitative data: Part five].

PMID- 19583944
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      an analysis of the mechanism of diseases (Part 2).

PMID- 19583945
TI  - Beta testing the antioxidant function of eIF2alpha phosphorylation in diabetes
      prevention.
AB  - In this issue of Cell Metabolism, Kaufman and colleagues (Back et al., 2009)
      elegantly demonstrate that appropriate regulation of eIF2alpha phosphorylation
      improves glucose tolerance and beta cell viability by preventing the lethal
      buildup of oxidative damage due to unregulated synthesis, trafficking, and
      misfolding of proteins.

PMID- 19583946
TI  - Spreading the wealth: Niemann-Pick type C proteins bind and transport
      cholesterol.
AB  - Endocytosed cholesterol must be transferred from the environment (e.g., low
      density lipoproteins) via the lysosomal system to the rest of the cell. In
      Niemann-Pick type C disease, this process fails. In a recent issue of Cell, Kwon
      et al. (2009) suggest how this transpires mechanistically by crystallizing a
      domain of a protein defective in this syndrome.

PMID- 19583947
TI  - A crystallized view of AMPK activation.
AB  - AMP-activated protein kinase (AMPK) is a key metabolic regulator. Recent work
      (Chen et al., 2009) elucidates the structural interaction between the
      autoinhibitory sequence and the kinase domain of the AMPK catalytic subunit.
      Enhanced understanding of the molecular mechanics of AMPK activation might lead
      to novel therapeutic approaches.

PMID- 19583948
TI  - The gutsy side of bone.
AB  - Though surgical removal of the stomach has long been linked to low bone mass, the
      molecular mechanism has been elusive. Amling and coworkers now demonstrate that
      gastric cell acid production is necessary for calcium absorption. Mice lacking
      this acidification develop hypocalcemia, with increased parathyroid hormone and
      osteoclast differentiation, and decreased bone mass.

PMID- 19583949
TI  - As a matter of fat.
AB  - Excess fatty acid accumulation in nonadipose tissues is a hallmark of metabolic
      disease. When elevated lipid levels exceed the cell's capacity to store or
      utilize fatty acids, a lipotoxic-response is elicited, characterized by
      destruction of organelle membranes, activation of stress pathways, and apoptosis.
      This Minireview focuses on the mechanisms by which lipid overload causes
      nonadipose cell death and contributes to the pathogenesis of obesity and
      diabetes.

PMID- 19583950
TI  - Translation attenuation through eIF2alpha phosphorylation prevents oxidative
      stress and maintains the differentiated state in beta cells.
AB  - Accumulation of unfolded protein within the endoplasmic reticulum (ER) attenuates
      mRNA translation through PERK-mediated phosphorylation of eukaryotic initiation
      factor 2 on Ser51 of the alpha subunit (eIF2alpha). To elucidate the role of
      eIF2alpha phosphorylation, we engineered mice for conditional expression of
      homozygous Ser51Ala mutant eIF2alpha. The absence of eIF2alpha phosphorylation in
      beta cells caused a severe diabetic phenotype due to heightened and unregulated
      proinsulin translation; defective intracellular trafficking of ER cargo proteins;
      increased oxidative damage; reduced expression of stress response and beta-cell
      specific genes; and apoptosis. However, glucose intolerance and beta cell death
      in these mice were attenuated by a diet containing antioxidant. We conclude that
      phosphorylation of eIF2alpha coordinately attenuates mRNA translation, prevents
      oxidative stress, and optimizes ER protein folding to support insulin production.
      The finding that increased proinsulin synthesis causes oxidative damage in beta
      cells may reflect events in the beta cell failure associated with insulin
      resistance in type 2 diabetes.

PMID- 19583951
TI  - Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha
      expression and adipogenesis.
AB  - PPARgamma and C/EBPalpha cooperate to control preadipocyte differentiation
      (adipogenesis). However, the factors that regulate PPARgamma and C/EBPalpha
      expression during adipogenesis remain largely unclear. Here, we show PTIP, a
      protein that associates with histone H3K4 methyltransferases, regulates PPARgamma
      and C/EBPalpha expression in mouse embryonic fibroblasts (MEFs) and during
      preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of
      PPARgamma expression and PPARgamma-stimulated C/EBPalpha expression. Further,
      PTIP is essential for induction of PPARgamma and C/EBPalpha expression during
      preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4
      trimethylation and RNA polymerase II on PPARgamma and C/EBPalpha promoters.
      Accordingly, PTIP(-/-) MEFs and preadipocytes all show striking defects in
      adipogenesis. Rescue of the adipogenesis defect in PTIP(-/-) MEFs requires
      coexpression of PPARgamma and C/EBPalpha. Finally, deletion of PTIP in brown
      adipose tissue significantly reduces tissue weight. Thus, by regulating PPARgamma
      and C/EBPalpha expression, PTIP plays a critical role in adipogenesis.

PMID- 19583952
TI  - Pigment epithelium-derived factor contributes to insulin resistance in obesity.
AB  - Obesity is a major risk factor for insulin resistance; however, the factors
      linking these disorders are not well defined. Herein, we show that the
      noninhibitory serine protease inhibitor, pigment epithelium-derived factor
      (PEDF), plays a causal role in insulin resistance. Adipocyte PEDF expression and
      serum levels are elevated in several rodent models of obesity and reduced upon
      weight loss and insulin sensitization. Lean mice injected with recombinant PEDF
      exhibited reduced insulin sensitivity during hyperinsulinemic-euglycemic clamps.
      Acute PEDF administration activated the proinflammatory serine/threonine kinases
      c-Jun terminal kinase and extracellular regulated kinase in both muscle and
      liver, which corresponded with reduced insulin signal transduction. Prolonged
      PEDF administration stimulated adipose tissue lipolysis, resulted in ectopic
      lipid deposition, and reduced insulin sensitivity, while neutralizing PEDF in
      obese mice enhanced insulin sensitivity. Overall, these results identify a causal
      role for PEDF in obesity-induced insulin resistance.

PMID- 19583953
TI  - Genetic evidence supporting a critical role of endothelial caveolin-1 during the
      progression of atherosclerosis.
AB  - The accumulation of LDL-derived cholesterol in the artery wall is the initiating
      event that causes atherosclerosis. However, the mechanisms that lead to the
      initiation of atherosclerosis are still poorly understood. Here, by using
      endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we
      show the critical role of Cav-1 in promoting atherogenesis. Mice were generated
      lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double
      knockout background. Genetic ablation of Cav-1 on an apoE knockout background
      inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the
      endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces
      LDL infiltration into the artery wall, promotes nitric oxide production, and
      reduces the expression of leukocyte adhesion molecules, effects completely
      reversed in transgenic mice. In summary, this unique model provides physiological
      evidence supporting the important role of endothelial Cav-1 expression in
      regulating the entry of LDL into the vessel wall and the initiation of
      atherosclerosis.

PMID- 19583955
TI  - Identification of cholesterol-regulating genes by targeted RNAi screening.
AB  - Elevated plasma cholesterol levels are considered responsible for excess
      cardiovascular morbidity and mortality. Cholesterol in plasma is tightly
      controlled by cholesterol within cells. Here, we developed and applied an
      integrative functional genomics strategy that allows systematic identification of
      regulators of cellular cholesterol levels. Candidate genes were identified by
      genome-wide gene-expression profiling of sterol-depleted cells and systematic
      literature queries. The role of these genes in cholesterol regulation was then
      tested by targeted siRNA knockdown experiments quantifying cellular cholesterol
      levels and the efficiency of low-density lipoprotein (LDL) uptake. With this
      strategy, 20 genes were identified as functional regulators of cellular
      cholesterol homeostasis. Of these, we describe TMEM97 as SREBP target gene that
      under sterol-depleted conditions localizes to endo-/lysosomal compartments and
      binds to LDL cholesterol transport-regulating protein Niemann-Pick C1 (NPC1).
      Taken together, TMEM97 and other factors described here are promising to yield
      further insights into how cells control cholesterol levels.

PMID- 19583954
TI  - CRTC2 (TORC2) contributes to the transcriptional response to fasting in the liver
      but is not required for the maintenance of glucose homeostasis.
AB  - The liver contributes to glucose homeostasis by promoting either storage or
      production of glucose, depending on the physiological state. The cAMP response
      element-binding protein (CREB) is a principal regulator of genes involved in
      coordinating the hepatic response to fasting, but its mechanism of gene
      activation remains controversial. We derived CRTC2 (CREB-regulated transcription
      coactivator 2, previously TORC2)-deficient mice to assess the contribution of
      this cofactor to hepatic glucose metabolism in vivo. CRTC2 mutant hepatocytes
      showed reduced glucose production in response to glucagon, which correlated with
      decreased CREB binding to several gluconeogenic genes. However, despite
      attenuated expression of CREB target genes, including PEPCK, G6Pase, and PGC
      1alpha, no hypoglycemia was observed in mutant mice. Collectively, these results
      provide genetic evidence supporting a role for CRTC2 in the transcriptional
      response to fasting, but indicate only a limited contribution of this cofactor to
      the maintenance of glucose homeostasis.

PMID- 19583956
TI  - Selenium functionalized intraocular lenses inhibit posterior capsule
      opacification in an ex vivo canine lens capsular bag assay.
AB  - The purpose of this study was to determine the inhibitory effect of
      selenocystamine coated intraocular lenses (IOLs) on the formation of posterior
      capsule opacification (PCO) in an ex vivo canine lens capsular bag assay.
      Selenocystamine was covalently bound to the surface of poly(2-hydroxyethyl
      methacrylate) (poly(HEMA)) discs. Three groups of canine lens capsules (6 coated
      IOLs (SeIOLs), 7 non-coated control IOLs and 8 empty capsules) were cultured for
      10 days. During the culture period PCO was scored based on visual inspection of
      the capsules using phase contrast microscopy. On day 10 all the capsules were
      prepared for light microscopic examination and lens epithelial cells (LECs) were
      quantified. Proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin
      (alpha-SMA) and cleaved caspase-3 were examined by immunohistochemistry.
      Additionally, cell viability assays were performed on LECs cultured in tissue
      culture medium pre-incubated with either a SeIOL or control IOL. The viability
      assays demonstrated that no detectable cytotoxic leachables were associated with
      the functionalized IOLs. The central posterior capsule was free of cells
      underneath all SeIOLs, although large numbers of LECs populated the capsular
      periphery. Apoptotic cells were observed underneath the periphery of some SeIOLs.
      Both the PCO scores and LEC counts of SeIOL containing capsules were
      significantly lower than those of control group capsules (p < 0.01 and p =
      0.0004, respectively). The use of selenium functionalized IOLs resulted in a
      significant reduction of PCO in this ex vivo model. Binding of selenocystamine to
      a foldable IOL may provide an effective method to prevent population of the
      central posterior capsule with LECs.

PMID- 19583957
TI  - A single immunization with a recombinant canine adenovirus type 2 expressing the
      seoul virus Gn glycoprotein confers protective immunity against seoul virus in
      mice.
AB  - Seoul virus (SEOV), a member of hantavirus genus, is one of the causative agents
      of hemorrhagic fever with renal syndrome (HFRS) and afflicts tens of thousands of
      people annually. In this paper, we evaluate the immune response induced by a
      replication-competent recombinant canine adenovirus type 2 expressing the Gn
      protein of SEOV (rCAV-2-Gn) in BALB/c mice. Sera from immunized mice contained
      neutralizing antibodies that could specifically recognize SEOV and neutralize its
      infectivity in vitro. Moreover, the recombinant virus induced complete protection
      against a lethal challenge with the highly virulent SEOV strain CC-2. Protective
      level neutralizing antibodies were maintained for at least 20 weeks. The efficacy
      of the recombinant was similar to that induced by a currently available
      inactivated HFRS vaccine. This recombinant virus is therefore a potential
      alternative to the inactivated vaccine.

PMID- 19583958
TI  - p38 MAPK inhibition selectively mitigates inflammatory mediators and VEGF
      production in AF cells co-cultured with activated macrophage-like THP-1 cells.
AB  - OBJECTIVES: Recent data have suggested that macrophages are involved in the
      pathogenesis of discogenic back pain and enhance the secretion of inflammatory
      mediators in co-cultured annulus fibrosus (AF) cells. The purpose of these
      studies is to determine the role of p38 mitogen-activated protein kinase (p38
      MAPK) signaling in the interactions between macrophage and AF cells. METHODS:
      Human AF cells were co-cultured with phorbol myristate acetate-stimulated
      macrophage-like THP-1 cells with and without p38 MAPK inhibition. Conditioned
      media from co-cultured cells were assayed for interleukin (IL)-6, IL-8,
      prostaglandin E2 (PGE2), PGF2alpha, and vascular endothelial growth factor
      (VEGF). Naive and macrophage-exposed AF cell responses to 10ng/ml tumor necrosis
      factor-alpha (TNF-alpha) were compared using the same outcome measures. RESULTS:
      IL-6, IL-8, PGE2, PGF2alpha, and VEGF were secreted in greater quantities by
      cells maintained in co-culture compared to macrophages or AF cells cultured
      alone. SB202190 blunted IL-6, PGE2, and PGF2alpha production in a dose-dependent
      manner in co-culture. However, it did not suppress IL-8 and VEGF production. TNF
      alpha-stimulated AF cell inflammatory mediators were up-regulated by macrophage
      exposure. SB202190 successfully suppressed IL-6, IL-8, PGE2, and PGF2alpha
      secretion in macrophage-exposed AF cells in response to TNF-alpha. CONCLUSIONS:
      Annular injury can result in macrophage infiltration, and this can cause enhanced
      inflammatory mediator and VEGF production by AF cells. The p38 MAPK pathway
      signals are responsible for much of IL-6 and PG secretion from AF cells with
      macrophage-like cells, suggesting that blockade of this signal may serve as a
      therapeutic approach to discogenic pain.

PMID- 19583959
TI  - Bone marrow lesions and joint effusion are strongly and independently associated
      with weight-bearing pain in knee osteoarthritis: data from the osteoarthritis
      initiative.
AB  - OBJECTIVE: It is widely believed that there are multiple sources of pain at a
      tissue level in osteoarthritis (OA). Magnetic Resonance Images (MRIs) provide a
      wealth of anatomic information and may allow identification of specific features
      associated with pain. We hypothesized that in knees with OA, bone marrow lesions
      (BMLs), synovitis, and effusion would be associated with weight-bearing and (less
      so with) non-weight-bearing pain independently. METHODS: In a cross-sectional
      study of persons with symptomatic knee OA using univariate and multivariate
      logistic regressions with maximal BML, effusion, and synovitis defined by Boston
      Leeds Osteoarthritis Knee Score as predictors, and knee pain using weight-bearing
      and non-weight-bearing Western Ontario and McMaster University OA Index pain
      questions as the outcome, we tested the association between MRI findings and knee
      symptoms. RESULTS: 160 participants, mean age 61 (+/-9.9), mean body mass index
      (BMI) 30.3 (+/-4.7) and 50% female, stronger associations were seen with weight
      bearing compared with non-weight-bearing knee pain with adjusted risk ratios
      (RRs) of weight-bearing knee pain, for increasing maximal BML scores of 1.0
      (referent) (maximal BML=0), 1.2, 1.9, and 2.0 (P for trend=0.006). For effusion
      scores, adjusted RRs of knee pain were 1.0, 1.7, 2.0, and 2.6 (P for
      trend=0.0004); and for synovitis scores, adjusted ORs were 1.0, 1.4, 1.5, and 1.9
      (P for trend=0.22). CONCLUSION: Cross-sectionally, maximal BML and effusion
      scores are independently associated with weight-bearing and less so with non
      weight-bearing knee pain, supporting the idea that pain in OA is multifactorial.
      These MRI features should be considered as possible new treatment targets in knee
      OA.

PMID- 19583960
TI  - Need for high-standard translation methodology for the dissemination of
      guidelines.

PMID- 19583961
TI  - TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis:
      modulation and integration of signaling pathways through receptor-Smads.
AB  - OBJECTIVE: Chondrocytes and alteration in chondrocyte differentiation play a
      central role in osteoarthritis. Chondrocyte differentiation is amongst others
      regulated by members of the transforming growth factor-beta (TGF-beta)
      superfamily. The major intracellular signaling routes of this family are via the
      receptor-Smads. This review is focused on the modulation of receptor-Smad
      signaling and how this modulation can affect chondrocyte differentiation and
      potentially osteoarthritis development. METHODS: Peer reviewed publications
      published prior to April 2009 were searched in the Pubmed database. Articles that
      were relevant for the role of TGF-beta superfamily/Smad signaling in chondrocyte
      differentiation and for differential modulation of receptor-Smads were selected.
      RESULTS: Chondrocyte terminal differentiation is stimulated by Smad1/5/8
      activation and inhibited the by Smad2/3 pathway, most likely by modulation of
      Runx2 function. Several proteins and signaling pathways differentially affect
      Smad1/5/8 and Smad2/3 signaling. This will result in an altered Smad1/5/8 and
      Smad2/3 balance and subsequently have an effect on chondrocyte differentiation
      and osteoarthritis development. CONCLUSION: Modulation of receptor-Smads
      signaling can be expect to play an essential role in both the regulation of
      chondrocyte differentiation and osteoarthritis development and progression.

PMID- 19583962
TI  - Differential binding of tropomyosin isoforms to actin modified with m
      maleimidobenzoyl-N-hydroxysuccinimide ester and fluorescein-5-isothiocyanate.
AB  - Differential interactions of tropomyosin (TM) isoforms with actin can be
      important for determination of the thin filament functions. A mechanism of
      tropomyosin binding to actin was studied by comparing interactions of five
      alphaTM isoforms with actin modified with m-maleimidobenzoyl-N-hydroxysuccinimide
      ester (MBS) and with fluorescein-5-isothiocyanate (FITC). MBS attachment sites
      were revealed with mass spectrometry methods. We found that the predominant actin
      fraction was cross-linked by MBS within subdomain 3. A smaller fraction of the
      modified actin was cross-linked within subdomain 2 and between subdomains 2 and
      1. Moreover, investigated actins carried single labels in subdomains 1, 2, and 3.
      Such extensive modification caused a large decrease in actin affinity for
      skeletal and smooth muscle tropomyosins, nonmuscle TM2, and chimeric TM1b9a. In
      contrast, binding of nonmuscle isoform TM5a was less affected. Isoform's affinity
      for actin modified in subdomain 2 by binding of FITC to Lys61 was intermediate
      between the affinity for native actin and MBS-modified actin except for TM5a,
      which bound to FITC-actin with similar affinity as to actin modified with MBS.
      The analysis of binding curves according to the McGhee-von Hippel model revealed
      that binding to an isolated site, as well as cooperativity of binding to a
      contiguous site, was affected by both actin modifications in a TM isoform
      specific manner.

PMID- 19583963
TI  - A new homogeneous high-throughput screening assay for profiling compound activity
      on the human ether-a-go-go-related gene channel.
AB  - Long QT syndrome, either inherited or acquired from drug treatments, can result
      in ventricular arrhythmia (torsade de pointes) and sudden death. Human ether-a-go
      go-related gene (hERG) channel inhibition by drugs is now recognized as a common
      reason for the acquired form of long QT syndrome. It has been reported that more
      than 100 known drugs inhibit the activity of the hERG channel. Since 1997,
      several drugs have been withdrawn from the market due to the long QT syndrome
      caused by hERG inhibition. Food and Drug Administration regulations now require
      safety data on hERG channels for investigative new drug (IND) applications. The
      assessment of compound activity on the hERG channel has now become an important
      part of the safety evaluation in the process of drug discovery. During the past
      decade, several in vitro assay methods have been developed and significant
      resources have been used to characterize hERG channel activities. However,
      evaluation of compound activities on hERG have not been performed for large
      compound collections due to technical difficulty, lack of throughput, and/or lack
      of biological relevance to function. Here we report a modified form of the FluxOR
      thallium flux assay, capable of measuring hERG activity in a homogeneous 1536
      well plate format. To validate the assay, we screened a 7-point dilution series
      of the LOPAC 1280 library collection and reported rank order potencies of ten
      common hERG inhibitors. A correlation was also observed for the hERG channel
      activities of 10 known hERG inhibitors determined in this thallium flux assay and
      in the patch clamp experiment. Our findings indicate that this thallium flux
      assay can be used as an alternative method to profile large-volume compound
      libraries for compound activity on the hERG channel.

PMID- 19583964
TI  - A one-step method to identify MAP kinase residues involved in inactivation by
      tyrosine- and dual-specificity protein phosphatases.
AB  - MAP kinases (MAPKs) are enzymes directly involved in the control of cellular
      homeostasis in response to external cues, from differentiation and developmental
      processes to cell transformation. The activation status of MAPKs, both in
      magnitude and in duration, reflects the balance of phosphorylation at their Thr
      and Tyr regulatory residues by specific MAPK kinases and their dephosphorylation
      by inactivating protein serine/threonine phosphatases (PPs) and protein tyrosine
      phosphatases (PTPs). The dephosphorylation of MAPKs by PTPs relies on molecular
      docking between the two enzymes at specific interaction sites. Here we outline a
      one-step method to identify ERK1/2 and p38alpha mutations that prevent binding
      and inactivation by PTPs (tyrosine- or dual-specificity phosphatases) based on
      the use of anti-pTyr antibodies and cell lysis buffers lacking or containing the
      broad PTP inhibitor sodium orthovanadate (Na3VO4).

PMID- 19583965
TI  - Hydrogel-based protein array for quantifying epidermal growth factor receptor
      activity in cell lysates.
AB  - Epidermal growth factor receptor (EGFR) signaling plays an important role in a
      majority of solid tumors, and therapeutics targeted against EGFR has demonstrated
      promise in slowing growth of these tumors. However, many of these drugs either
      have failed to reproduce promising preclinical model results in clinical settings
      or have been successful in only a subgroup of cancer patients due partly to
      incomplete assessment of EGFR status in cancer. A patient-customized, predictive
      diagnostic for the effects of specific anti-EGFR therapies may improve outcomes.
      Here we report the development of a hydrogel-based protein array for quantitative
      and reproducible determination of the activity of EGFR directly from cellular
      extracts. In this study, we used glutathione S-transferase-fused Eps15 (GST
      Eps15) fusion proteins immobilized within a polyacrylamide hydrogel as a
      substrate for quantifying EGFR kinase activity from the extracts of EGFR
      expressing cell lines. Significant EGFR up-regulation was detected in a mixture
      containing 7% EGFR-overexpressing cell lysate diluted in lysate from a cell line
      expressing low levels of EGFR. In addition, the GST-Eps15 protein array was
      capable of detecting inhibition of EGFR activity when incubated with different
      tyrosine kinase inhibitors. These findings establish the potential of this
      protein-acrylamide copolymer hydrogel array not only to evaluate EGFR status in
      cancer cell lysates but also to screen for the most promising therapeutics for
      individual patients and monitor treatment progression.

PMID- 19583967
TI  - Trypanosoma cruzi: Different methods of data analysis to evaluate the genetics
      biology relationship.
AB  - The correlation of genetic and biological diversity in Trypanosoma cruzi was
      studied. Strains of T. cruzi II, isolated from humans; and of T. cruzi I,
      isolated from wild-animal reservoirs and from triatomines in the state of Parana,
      Brazil, were used. Thirty-six biological parameters measured in vitro and six in
      vivo, related to growth kinetics and metacyclogenesis, susceptibility to
      benznidazole, macrophage infection, and experimental infection in mice were
      evaluated. Data from RAPD and SSR-PCR were used as genetic parameters. Mantel's
      test, group analysis, principal components analysis (PCA), and cladistical
      analyses were applied. With the Mantel's test, a low correlation was observed
      when parameters related to growth kinetics and metacyclogenesis in vitro and
      development of the experimental infection in vivo were included. The group
      analysis defined two groups that were separated as to whether they produced
      patent parasitemia in BALB/c mice. In the larger group, strains derived from wild
      reservoirs were separated from strains derived from triatomines and humans. The
      PCA identified two groups that differed as to whether they produced a parasitemia
      curve in mice. The cladistical analysis supported the previous results. This
      study shows the importance of the parasite-host relationship for the behavior of
      the strains, and that the combination of methods supports, extends, and clarifies
      the available information.

PMID- 19583968
TI  - Propagation of the myxozoan parasite Myxobolus cerebralis by different geographic
      and genetic populations of Tubifex tubifex: an Oregon perspective.
AB  - Tubifex tubifex are obligate invertebrate hosts in the life cycle of Myxobolus
      cerebralis, the myxozoan parasite that causes whirling disease in salmonid
      fishes. This exotic parasite is established to varying degrees across Oregon's
      Columbia River system (Pacific Northwest, USA) and characteristics of local T.
      tubifex populations likely play a role in the pattern of disease occurrence. To
      better understand these patterns, we collected T. tubifex from three Oregon river
      basins (Willamette, Deschutes, and Grande Ronde), determined their genotype
      (mitochondrial 16S rDNA lineage and RAPD genotype) and exposed 10 different
      populations to M. cerebralis in the laboratory. Four mt lineages were identified:
      I, III, V and VI. Lineage III was found in all river basins but dominated both
      central and eastern sites. The RAPD assay further divided these lineages into
      geographic sub-populations; no RAPD genotype was common to all basins. There was
      a significant difference in prevalence of infection and level of parasite
      production among the populations we exposed to M. cerebralis that was attributed
      to genotypic composition. Only lineage III worms released actinospores and only
      populations dominated by this lineage amplified the parasite. These populations
      had the lowest survival, however, the lineage dominant before exposure remained
      dominant despite the high prevalence of infection. The distribution and infection
      dynamics of susceptible T. tubifex throughout Oregon may contribute to the
      differences in M. cerebralis occurrence; our studies further support the
      influence of oligochaete genotypes on the manifestation of whirling disease in
      salmonid populations.

PMID- 19583966
TI  - Conformational changes and catalysis by alcohol dehydrogenase.
AB  - As shown by X-ray crystallography, horse liver alcohol dehydrogenase undergoes a
      global conformational change upon binding of NAD(+) or NADH, involving a rotation
      of the catalytic domain relative to the coenzyme binding domain and the closing
      up of the active site to produce a catalytically efficient enzyme. The
      conformational change requires a complete coenzyme and is affected by various
      chemical or mutational substitutions that can increase the catalytic turnover by
      altering the kinetics of the isomerization and rate of dissociation of coenzymes.
      The binding of NAD(+) is kinetically limited by a unimolecular isomerization
      (corresponding to the conformational change) that is controlled by deprotonation
      of the catalytic zinc-water to produce a negatively-charged zinc-hydroxide, which
      can attract the positively-charged nicotinamide ring. The deprotonation is
      facilitated by His-51 acting through a hydrogen-bonded network to relay the
      proton to solvent. Binding of NADH also involves a conformational change, but the
      rate is very fast. After the enzyme binds NAD(+) and closes up, the substrate
      displaces the hydroxide bound to the catalytic zinc; this exchange may involve a
      double displacement reaction where the carboxylate group of a glutamate residue
      first displaces the hydroxide (inverting the tetrahedral coordination of the
      zinc), and then the exogenous ligand displaces the glutamate. The resulting
      enzyme-NAD(+)-alcoholate complex is poised for hydrogen transfer, and small
      conformational fluctuations may bring the reactants together so that the hydride
      ion is transferred by quantum mechanical tunneling. In the process, the
      nicotinamide ring may become puckered, as seen in structures of complexes of the
      enzyme with NADH. The conformational changes of alcohol dehydrogenase demonstrate
      the importance of protein dynamics in catalysis.

PMID- 19583969
TI  - 6beta-naltrexol preferentially antagonizes opioid effects on gastrointestinal
      transit compared to antinociception in mice.
AB  - AIMS: The current studies were designed to compare the in vivo potencies of the
      opioid antagonists 6beta-naltrexol and naltrexone in blocking the effects of the
      opioid agonist hydrocodone following intravenous (i.v.) or oral (p.o.)
      administration. MAIN METHODS: Adult male CD-1 mice were used for all experiments.
      The 55 degrees C tail-flick assay was used to assess the CNS antinociceptive
      activity of hydrocodone, and a charcoal meal gastrointestinal transit assay was
      used to assess the peripheral effects of hydrocodone. Graded antagonist dose
      response curves for i.v. and p.o. 6beta-naltrexol and naltrexone were generated
      to determine ID(50) antagonist potency estimates against fixed doses of
      hydrocodone. KEY FINDINGS: Both antagonists produced dose-related blockade of
      hydrocodone-induced antinociception and inhibition of gastrointestinal transit.
      Naltrexone was between 5- and 13-fold more potent than 6beta-naltrexol in
      blocking a CNS effect of hydrocodone, whereas the drugs were nearly equipotent in
      blocking inhibition of gastrointestinal transit. Co-administration studies
      indicated an approximate 10-fold greater potency of 6beta-naltrexol for
      antagonism of hydrocodone-induced inhibition of gastrointestinal transit versus
      antinociception, whereas naltrexone blocked both effects with near equal potency.
      6beta-naltrexol produced a longer duration of antagonist blockade and had a
      slower time to peak effect compared to naltrexone. SIGNIFICANCE: The pharmacology
      of 6beta-naltrexol differentiates it from currently available opioid antagonists.
      This includes an intermediate selectivity for peripheral versus central opioid
      receptors, a long duration of action, and neutral antagonist qualities in opioid
      exposed systems. These properties render it a drug candidate for a co-formulation
      product with opioid analgesics to reduce peripheral opioid side effects and limit
      abuse potential.

PMID- 19583971
TI  - Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation
      related bone disease.
AB  - Chronic inflammation affects bone metabolism and is commonly associated with the
      presence of osteoporosis. Bone loss is directed by various immune mediators such
      as the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin 1
      beta or interferon-gamma. Pre-B cell colony enhancing factor (PBEF)/nicotinamide
      phosphoribosyl transferase (NAMPT)/visfatin is a pleiotropic mediator acting as
      growth factor, cytokine and enzyme involved in energy and nicotinamide adenine
      dinucleotide (NAD) metabolism. PBEF/NAMPT/visfatin has been recently demonstrated
      to exert several pro-inflammatory functions. We studied serum levels of
      PBEF/NAMPT/visfatin in patients with inflammatory bowel diseases (IBD) and their
      relation with bone mineral density (BMD). Furthermore, we were interested whether
      PBEF/NAMPT/visfatin affects osteoclastogenesis and involved mediators.
      PBEF/NAMPT/visfatin serum levels were increased in patients with IBD, correlated
      positively with disease activity and negatively with BMD, especially in the
      lumbar spine. Osteoclast precursor cells were generated from peripheral blood
      mononuclear cells after stimulation with various growth factors such as
      macrophage colony-stimulating factor (M-CSF) and soluble ligand of receptor
      activator of nuclear factor kappa B (RANK). In these in vitro studies,
      PBEF/NAMPT/visfatin suppressed osteoclastogenesis and inhibited the
      differentiation of osteoclast precursors into tartrate-resistant acid phosphatase
      positive multinucleated cells. These effects were paralleled by the suppression
      of the osteoclast typical markers RANK, nuclear factor of activated T-cells c1
      (NFATc1) and cathepsin-K. This is the first report demonstrating a potential role
      for this important cytokine/enzyme in inflammation-related bone disease.

PMID- 19583970
TI  - Antenatal glucocorticoid therapy increase cardiac alpha-enolase levels in fetus
      and neonate rats.
AB  - AIMS: Antenatal glucocorticoid therapy has been shown to prevent acute diseases
      including infant respiratory distress syndrome and reduce mortality, although
      little is known about the effects on cardiac function-related proteins in the
      fetus or neonate. We investigated whether cardiac function-related proteins were
      altered in cardiac tissues of fetuses and neonates born to pregnant rats treated
      by glucocorticoid. MAIN METHODS: Dexamethasone (DEX) was administered to pregnant
      rats for 2 days on day 17 and 18 or day 19 and 20 of gestation to simulate
      antenatal DEX therapy, and cardiac tissues of 19- and 21-day fetuses and 1-, 3-,
      and 5-day neonates were analyzed using a proteomic technique with liquid
      chromatography-mass spectrometry/mass spectrometry. KEY FINDINGS: The identified
      five proteins; alpha-enolase, creatine kinase-M type, beta-tubulin, troponin T,
      and ATP synthase beta-chain, were significantly increased in fetal cardiac
      tissues with DEX administration. We observed that significant increase of alpha
      enolase in the 19-day fetuses by DEX using Western blotting and
      immunohistochemistry. ATP and cAMP levels were also increased in the fetal heart
      tissue. In addition, pyruvate levels were significantly increased in the fetus
      groups by DEX. SIGNIFICANCE: These results suggest that increased alpha-enolase
      may contribute to acceleration of glycolysis in the preterm heart.

PMID- 19583972
TI  - Effect of adiponectin deficiency on intestinal damage and hematopoietic responses
      of mice exposed to gamma radiation.
AB  - Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin
      sensitivity and inflammation. It is also involved in modulation of cell
      proliferation by binding to various growth factors. Based on its known effects in
      modulating cell proliferation and oxidative stress, APN may potentially be
      involved in regulating tissue damage and repair following irradiation.
      Adiponectin KO mice and their WT littermates were exposed to a single whole-body
      dose of 3 or 6Gy gamma radiation. Radiation-induced alterations were studied in
      jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and
      compared with sham-irradiated groups. In WT mice, irradiation did not
      significantly alter serum APN levels while inducing a significant decrease in
      serum leptin. Irradiation caused a significant reduction in thymocyte
      cellularity, with concomitant decrease in CD4(+), CD8(+) and CD4(+)CD8(+) T cell
      populations, with no significant differences between WT and APN KO mice.
      Irradiation resulted in a significantly higher increase in the frequency of
      micronucleated reticulocytes in the blood of APN KO compared with WT mice,
      whereas frequency of micronucleated normochromatic erythrocytes in the bone
      marrow at day 5 was significantly higher in WT compared with APN KO mice.
      Finally, irradiation induced similar alterations in villus height and crypt cell
      proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham
      irradiated APN KO mice produced higher levels of IL-6 compared with tissue from
      WT animals, but the difference was no longer apparent following irradiation. Our
      data indicate that APN deficiency does not play a significant role in modulating
      radiation-induced gastrointestinal injury in mice, while it may participate in
      regulation of damage to the hematopoietic system.

PMID- 19583973
TI  - The possible effect of transposons on the Drosophila melanogaster somatic
      mutation and recombination test.
AB  - The wing somatic mutation and recombination test (SMART) using transheterozygotes
      for the Drosophila melanogaster third chromosome markers mwh (multiple wing
      hairs) and flr(3) (flare-3) has proved to be efficient in genotoxicity screens.
      The genetic background of the D. melanogaster strains affects the frequency of
      identification of somatic mutant spots. The genetic background appears to be also
      of importance in hybrid dysgenesis (HD) revealed in crosses between flies from
      genetically distant D. melanogaster strains. In this study, we analyzed mwh and
      flr3/Ser D. melanogaster strains for the presence of the P and hobo transposable
      elements that induce genetic instability in P-M and H-E dysgenic crosses,
      respectively. According to PCR these strains lack the P-element. The mwh strain
      does not contain the hobo-element too, while hobo is present as a full-length
      variant and its numerous defective derivatives in the flr(3)/Ser genome. Based on
      the crosses the reference E- and H-strains to strains used in SMART, the flr/Ser
      were assigned to the H-type and the mwh to the E-type. Fluorescence in situ
      hybridization reveals over 50 hobo hybridization sites scattered throughout the
      flr(3)/Ser genome. Thus, there is a basis for H-E HD in the strains we studied.
      However the mwh/flr(3), regardless of cross-direction showed higher fertility
      than the mwh females. Cross-direction had also no affect on hybrid fertility.
      This meant that they did not exhibit the major HD symptoms. In our view, the
      significance of the TE activity as a cause of HD has been overestimated, in the
      case of H-E HD at least. The majority of the mutant spots in SMART result not so
      much from mutations or TE transposition as from recombination events, even in the
      case of balancer individuals.

PMID- 19583974
TI  - Regulation of ATM in DNA double strand break repair accounts for the
      radiosensitivity in human cells exposed to high linear energy transfer ionizing
      radiation.
AB  - High linear energy transfer (LET) radiation shows different biological effects
      from low-LET radiation. The complex nature of high LET radiation-induced damage,
      especially the clustered DNA damage, brings about slow repair of DNA double
      strand breaks (DSBs), which finally lead to higher lethality and chromosome
      aberration. Ionizing radiation (IR) induced DNA DSBs are repaired by both non
      homologous end-joining (NHEJ) and homologous recombination repair (HRR) pathways
      in mammalian cells. The novel function of ataxia telangiectasia-mutated (ATM)
      protein is its involvement in the DSB repair of slow kinetics for "dirty" breaks
      rejoining by NHEJ, this suggests that ATM may play a more important role in high
      LET radiation-induced DNA damage. We show here that KU55933, an ATM inhibitor
      could distinctly lower the clonogenic survival in normal human skin fibroblast
      cells exposed to carbon ion radiation and dramatically impair the normal process
      for DSB repair. We also implicated the involvement of ATM in the two pathways of
      DNA DSB repair, with DNA-PKcs and Rad51 as the representative proteins. The
      phosphorylation of DNA-PKcs at Thr-2609 with both immunoblotting and
      immunofluorescent staining indicated an ATM-dependent change, while for Rad51,
      KU55933 pretreatment could postpone the formation of nuclear Rad51 foci.
      Interestingly, we also found that pretreatment with chloroquine, an ATM
      stimulator could protect cells from carbon ion radiation only at lower doses. For
      doses over 1Gy, protection was no longer observed. There was a dose-dependent
      increase for ATM kinase activity, with saturation at about 1Gy. Chloroquine
      pretreatment prior to 1Gy of carbon ion radiation did not enhance the
      autophosphorylation of ATM at serine 1981. The function of ATM in G2/M checkpoint
      arrest facilitated DSB repair in high-LET irradiation. Our results provide a
      possible mechanism for the direct involvement of ATM in DSB repair by high-LET
      irradiation.

PMID- 19583976
TI  - Olanzapine plus 17-beta estradiol produce antidepressant-like actions in rats
      forced to swim.
AB  - Several combinations of effective treatments have been used in the search for
      higher response rates or more rapid responses than monotherapy to diminish
      treatment-resistant depression. One strategy is to combine olanzapine plus
      antidepressant drugs. In preclinical studies in male rats, olanzapine combined
      with fluoxetine produce antidepressant-like actions and increase the
      allopregnanolone levels in the brain. 17-beta estradiol also produces
      antidepressant-like actions by increasing allopregnanolone levels. However, the
      effects of combining olanzapine with 17-beta estradiol in the forced swimming
      test have not been tested before. Thus, systemic injections of vehicle plus
      olanzapine, or fluoxetine (20.0 mg/kg; 25.0 mg/kg) or 17-beta estradiol (10.0
      microg/rat; 20.0 microg/rat) reduced immobility by increasing active behaviors,
      which were cancelled by finasteride (finasteride was used to block the endogenous
      production of allopregnanolone by the brain) in ovariectomized rats forced to
      swim. Subthreshold doses of olanzapine (2.5 mg/kg) combined with subthreshold
      doses of 17-beta estradiol (5.0 microg/rat) produced antidepressant-like actions,
      as did the combination subthreshold dose of olanzapine (2.5 mg/kg) plus the
      subthreshold dose of fluoxetine (15.0 mg/kg). Finasteride cancelled the
      antidepressant-like actions of the several combinations used. It is concluded
      that olanzapine alone or combined with fluoxetine or estradiol reduced immobility
      by increasing swimming. In conclusion, olanzapine produces antidepressant-like
      actions alone or in combination with estradiol. These antidepressant-like actions
      of this combination were cancelled by finasteride.

PMID- 19583975
TI  - Ondansetron blocks LiCl-induced conditioned place avoidance but not conditioned
      taste/flavor avoidance in rats.
AB  - The ability of an experimental agent to support conditioned taste/flavor
      avoidance (CT/FA) in rats often is interpreted as sufficient evidence that the
      agent produced a state of malaise or nausea. Paradoxically, however, CT/FA also
      is induced by certain drugs that support conditioned preferences in rats,
      suggesting that CT/FA is insufficient to reveal a negative hedonic state. The
      present study tested the hypothesis that the anti-nausea drug ondansetron (OND)
      would block the ability of nauseogenic lithium chloride (LiCl) to support
      conditioned place avoidance (CPA), without attenuating LiCl-induced CT/FA. After
      pre-treatment with either OND or vehicle, rats were conditioned with i.p.
      injection of 0.15 M LiCl containing 2% saccharin (LiCl+sac) on conditioning day
      1, and with 0.15 M NaCl alone on conditioning day 2. Rats were confined to a
      distinct chamber of a CPA apparatus after each conditioning injection. In other
      rats, OND or vehicle pre-treatment was followed by NaCl+sac on conditioning day
      1, and LiCl alone on day 2. Subsequent testing revealed that OND blocked the
      ability of LiCl to support CPA. Conversely, in the same rats, OND did not alter
      the ability of LiCl to condition avoidance of 0.2% sac solution during a 60 min
      bottle test. In a separate experiment, a sensitive 2-bottle choice test was used
      to confirm that OND pre-treatment does not reduce the ability of LiCl to support
      CT/FA. These results support the view that CPA is an additional useful tool to
      reveal the experience of malaise and nausea in rats, whereas CT/FA demonstrated
      in bottle intake tests is insufficient for this purpose.

PMID- 19583977
TI  - Immobilization of Candida rugosa lipase on sporopollenin from Lycopodium
      clavatum.
AB  - Sporopollenin is a natural polymer obtained from Lycopodium clavatum, which is
      highly stable with constant chemical structure and has high resistant capacity to
      chemical attack. In this study, immobilization of lipase from Candida rugosa
      (CRL) on sporopollenin by adsorption method is reported for the first time.
      Besides this, the enzyme adsorption capacity, activity and thermal stability of
      immobilized enzyme have also been investigated. It has been observed that under
      the optimum conditions (Spo-E((0.3))), the specific activity of the immobilized
      lipase on the sporopollenin by adsorption was 16.3U/mg protein, which is 0.46
      times less than that of the free lipase (35.6U/mg protein). The pH and
      temperature of immobilized enzyme were optimized, which were 6.0 and 40 degrees C
      respectively. Kinetic parameters V(max) and K(m) were also determined for the
      immobilized lipase. It was observed that there is an increase of the K(m) value
      (7.54mM) and a decrease of the V(max) value (145.0U/mg-protein) comparing with
      that of the free lipase.

PMID- 19583978
TI  - Agonist actions of clothianidin on synaptic and extrasynaptic nicotinic
      acetylcholine receptors expressed on cockroach sixth abdominal ganglion.
AB  - Clothianidin is new neonicotinoid insecticide acting selectively on insect
      nicotinic acetylcholine receptors (nAChRs). Its effects on nAChRs expressed on
      cercal afferent/giant interneuron synapses and DUM neurons have been studied
      using mannitol-gap and whole-cell patch-clamp techniques, respectively. Bath
      application of clothianidin-induced dose-dependent depolarizations of cockroach
      cercal afferent/giant interneuron synapses which were not reversed after wash-out
      suggesting a strong desensitization of postsynaptic interneurons at the 6th
      abdominal ganglion (A6). Clothinidin activity on the nerve preparation was
      characterized by an increased firing rate of action potentials which then ceased
      when the depolarization reached a peak. Clothianidin responses were insensitive
      to all muscarinic antagonists tested but were blocked by co-application of
      specific nicotinic antagonists methyllicaconitine, alpha-bungarotoxin and d
      tubocurarine. In a second round of experiment, clothianidin actions were tested
      on DUM neurons isolated from the A6. There was a strong desensitization of nAChRs
      which was not affected by muscarinic antagonists, pirenzepine and atropine, but
      was reduced with nicotinic antagonist alpha-bungarotoxin. In addition,
      clothianidin-induced currents were completely blocked by methyllicaconitine
      suggesting that (1) clothianidin acted as a specific agonist of nAChR subtypes
      and (2) a small proportion of receptors blocked by MLA was insensitive to alpha
      bungarotoxin. Moreover, because clothianidin currents were blocked by d
      tubocurarine and mecamylamine, we provided that clothianidin was an agonist of
      both nAChRs: imidacloprid-sensitive nAChR1 and -insensitive nAChR2 subtypes.

PMID- 19583979
TI  - Apolipoprotein E genotyping method by real time PCR, a fast and cost-effective
      alternative to the TaqMan and FRET assays.
AB  - The apolipoprotein E gene (APOE) polymorphism genotyping has an allegedly
      important predictive value for coronary heart disorders and Alzheimer's disease.
      We developed a simple, fast, cost-effective and suited for high-throughput
      protocol for determining APOE genotypes by Real Time PCR monitored by SYBR Green.
      The method is based on differential amplification by allele-specific primers.
      These primers have variations in their 3'-end nucleotides such that are specific
      for one of the two variants in each polymorphic position. By this protocol, we
      obtained a 100% concordance with the APOE genotypes determined by sequencing
      analysis. The main advantages of this method are its relative simplicity and the
      reduced cost compared to other methodologies, such as the TaqMan and FRET assays.

PMID- 19583980
TI  - Representing spike trains using constant sampling intervals.
AB  - Sensory neurons encode external information by a series of times of action
      potentials, which is called a spike train. However, since it is a point process,
      it is hard to analyze. Here we propose a method for converting a spike train into
      a real-valued time series with a fixed sampling interval under the assumption of
      temporal codes. The proposed method yields time series that represent encoded
      signals. Especially when the method is applied to spike trains generated using
      integrate-and-fire models, the yielded time series look very similar to those of
      encoded information. The method works robustly even when a spike train is
      contaminated with noise. Since unlike filters it does not use its original
      signals for the conversion, the proposed method can be widely used for
      investigating spike train data in the real world.

PMID- 19583981
TI  - In vivo labeling and in vitro characterisation of central complex neurons
      involved in the control of sound production.
AB  - Injection of muscarine into the central complex of the grasshopper brain can
      stimulate species-specific sound production through activation of the
      phospholipase C-initiated transduction pathway. We introduce a strategy, to label
      central complex interneurons that are directly stimulated by the injected
      muscarine and to study their physiology in dissociated primary cell culture.
      Fluorescent dextranes, co-injected to brain sites where muscarine stimulates
      sound production, are incorporated from the extracellular space by 3-14 central
      complex neurons. Most labeled neurons are columnar neurons that express
      muscarinic acetylcholine receptors. An average of 3-4 dextrane-labeled central
      complex neurons per brain can be recognised by their fluorescence in dissociated
      cell cultures. Their function as potential direct targets of previous in vivo
      pharmacological stimulation of the intact brain was supported by expression of
      muscarinic receptors in cytomembranes of isolated neuronal cell bodies and
      muscarine-stimulated calcium responses in vitro. Pharmacological inhibition of
      phospholipase C function and removal of extracellular calcium indicated that
      release from inositolphosphate-regulated internal stores mediates the increase of
      cytosolic calcium concentrations. The experimental procedures described in this
      study can be applied to any preparation in which focal drug application elicits,
      terminates or modulates behavior in order to label and physiologically analyse
      those interneurons within the circuit that serve as direct targets of the
      injected drug.

PMID- 19583982
TI  - A cellular model of inflammation for identifying TNF-alpha synthesis inhibitors.
AB  - Neuroinflammation is a common facet of both acute and chronic neurodegenerative
      conditions, exemplified by stroke and by Alzheimer's and Parkinson's disease, and
      the presence of elevated levels of the proinflammatory cytokine, tumor necrosis
      factor-alpha (TNF-alpha), has been documented in each. Although initial TNF-alpha
      generation is associated with a protective compensatory response, its unregulated
      chronic elevation is generally detrimental and can drive the disease process. In
      such circumstances, therapeutic strategies that can both gain access to the brain
      and target the production of TNF-alpha are predicted to be of clinical benefit.
      An in vitro mouse macrophage-like cellular screen, utilizing RAW 264.7 cells, was
      hence developed to identify novel TNF-alpha lowering agents incorporating
      lipophilic physicochemical characteristics predicted to allow penetration of the
      blood-brain barrier. Cultured RAW 264.7 cells exposed to lipopolysaccharide (LPS)
      induced a rapid, marked and concentration-dependent cellular release of TNF-alpha
      into the cell culture media, which was readily detected by enzyme linked
      immunosorbent assay (ELISA). The effects of four characterized thalidomide-based
      TNF-alpha lowering agents were assessed alongside 10 novel uncharacterized
      compounds synthesized on the same backbone. One of these new analogs possessed
      activity of sufficient magnitude to warrant further investigation. Activity
      determined in the cellular model translated to an in vivo rodent model of acute
      LPS-induced TNF-alpha elevation. The utility of the TNF-alpha cellular assay lies
      in its simplicity and robust nature, providing a tool for initial pharmacological
      screening to allow for the rapid identification novel TNF-alpha lowering agents.

PMID- 19583983
TI  - OpenFluo: a free open-source software for optophysiological data analyses.
AB  - Optophysiological imaging methods can be used to record the activity in vivo of
      groups of neurons from particular areas of the nervous system (e.g. the brain) or
      of cell cultures. Such methods are used, for example, in the spatio-temporal
      coding and processing of sensory information. However, the data generated by
      optophysiological methods must be processed carefully if relevant results are to
      be obtained. The raw fluorescence data must be digitally filtered and analyzed
      appropriately to obtain activity maps and fluorescence time course for single
      spots. We used a Matlab environment to implement the necessary procedures in a
      user-friendly manner. We developed OpenFluo, a program for people inexperienced
      in optophysiological methods and for advanced users wishing to perform simple,
      rapid data analyses without the need for complex, time-consuming programming
      procedures. This program will be made available as stand-alone software and as an
      open-source Matlab tool. It will therefore be possible for experienced users to
      integrate their own routines. We validated this software by assessing its ability
      to process both artificial recordings and real biological data corresponding to
      recordings of the honeybee brain.

PMID- 19583984
TI  - Behavioral profile and dorsal hippocampal cells in carioca high-conditioned
      freezing rats.
AB  - Selection for contextual fear conditioning is an important behavioral paradigm
      for studying the role of genetic variables and their interaction with the
      surrounding environment in the etiology and development of anxiety disorders.
      Recently, a new line of animals selectively bred for high levels of freezing in
      response to contextual cues previously associated with footshock was developed
      from a Wistar population. The purpose of the present study was to evaluate the
      emotional and cognitive aspects of this new line of animals, which has been named
      Carioca High-Freezing (CHF). For the characterization of anxious behavior, CHF
      and control animals were tested in the elevated plus-maze (EPM) and the social
      interaction test. CHF animals were significantly more anxious than control rats
      in terms of both the number of entries into EPM open arms and the percentage of
      time spent in these arms. The time spent in social interaction behavior was also
      significantly decreased. No statistical differences were found in locomotor
      activity, as measured by both the number of entries into the closed arms of the
      EPM and the number of crossings into the social interaction test arena. No
      differences between CHF and control groups were found in the depression forced
      swimming test, suggesting that the anxiety trait selected in the CHF line did not
      interact with affective disorders traits such as those for depression. Cognitive
      aspects of the CHF rats were evaluated in the object recognition task. Results
      from this test indicated no difference between the two groups. The present study
      also encompassed histological analysis of the dorsal hippocampus from CHF and
      control animals. Results revealed an absence of qualitative and quantitative
      differences between these two groups of animals in cells located in the dentate
      gyrus, CA1, and CA3 areas. Therefore, future studies are required to further
      investigate the possible neural mechanisms involved in the origin and development
      of the anxious phenotype observed in this model.

PMID- 19583985
TI  - The synthetic substance hypoxanthine 3-N-oxide elicits alarm reactions in
      zebrafish (Danio rerio).
AB  - Zebrafish, one of the preferred study species of geneticists, is gaining
      increasing popularity in behavioral neuroscience. This small and prolific species
      may be an excellent tool with which the biological mechanisms of vertebrate brain
      function and behavior are investigated. Zebrafish has been proposed as a model
      organism in the analysis of fear responses and human anxiety disorders. Species
      specific cues signaling the presence of predators have been successfully utilized
      in such research. Zebrafish has been shown to respond to its natural alarm
      substance with species-typical fear reactions. However, the extraction of this
      alarm substance and ascertaining its consistent dosing has been problematic. A
      synthetic substance with a known chemical identity and molecular weight would
      allow precise dosing and experimental control. Previously, the chemical
      component, hypoxanthine 3-N-oxide, common to several fish alarm substances has
      been identified and has been shown to elicit alarm reactions in fish species
      belonging to the Osteriophysan superorder. In the current study we investigate
      the effect of hypoxanthine 3-N-oxide by exposing zebrafish to three different
      concentrations of this synthetic substance. Our results show that the substance
      efficaciously induces species-typical fear reactions increasing the number of
      erratic movement episodes and jumps in zebrafish. We discuss the translational
      relevance of our findings and conclude that hypoxanthine 3-N-oxide will have
      utility to elicit fear responses in the laboratory in a precisely controlled
      manner in zebrafish.

PMID- 19583986
TI  - Simple quantification of bacterial envelope-associated extracellular materials.
AB  - We have developed a simple method for distinguishing between bacterial cultures
      that produce different amount of exopolysaccharide. It is based upon small
      differences in pellet volume formed by those cultures upon centrifugation. For
      that we have constructed a special centrifugation tube consisting of two
      connected chambers: an upper 12 ml chamber connected to a lower capillary
      chamber. Cells are applied to the upper chamber and following centrifugation,
      sink to its bottom and are forced into the capillary so that the height they fill
      can be measured. This procedure has been developed in order to demonstrate
      differences in volume of centrifugation pellet formed by similar number of
      Escherichia coli K12 wild type, rpoS mutant and yjbG rpoS double mutant cells.
      These differences are further shown to be a result of overproduction of colanic
      acid exopolysaccharide in the mutant strains. We suggest that this simple method
      can be employed to detect differences in other cell surface structures and to
      estimate biomass when optical density measurement or microscopic count is not
      applicable.

PMID- 19583987
TI  - Efficient in vitro synthesis of cis-polyisoprenes using a thermostable cis
      prenyltransferase from a hyperthermophilic archaeon Thermococcus kodakaraensis.
AB  - The Tk-idsB encoding cis-prenyltransferase which catalyzes consecutive cis
      condensation of isopentenyl diphosphate to allylic diphosphate was isolated from
      a hyperthermophilic archaeon Thermococcus kodakaraensis, and enzymatic
      characteristics of the recombinant Tk-IdsB were examined. Tk-IdsB was not fully
      denatured even at 90 degrees C and preferably utilizes both C(10) and C(15)
      allylic diphosphates to yield mainly the C(60)-C(65) products. Based on
      structural models, single alanine-substitution mutants at Glu68, Lys109, or
      Leu113 were constructed, showing that all the three produced longer chains (C(65)
      C(70)) than the wild-type and the substitution at 109 (K109A) was the most
      effective. Tk-IdsB was applied to an organic-aqueous dual-phase system and more
      than 90% of the products were recovered from the organic phase when 1-butanol or
      1-pentanol was overlaid. When 1-octanol was overlaid, 70% of the products were
      obtained from the upper organic phase. The product distributions were changed
      depending on the hydrophobicity of organic solvents used. Tk-IdsB was then
      immobilized onto silica beads to make Tk-IdsB more tolerant, showing that half
      life of enzyme at 80 degrees C was prolonged by immobilization. When the
      immobilized Tk-IdsB was applied in the organic-aqueous dual-phase system,
      immobilized Tk-IdsB catalyzed consecutive condensation more efficiently than the
      unimmobilized one.

PMID- 19583988
TI  - Transcriptional control of the succinate dehydrogenase operon sdhCAB of
      Corynebacterium glutamicum by the cAMP-dependent regulator GlxR and the LuxR-type
      regulator RamA.
AB  - In experiments performed to identify transcriptional regulators of the
      tricarboxylic acid cycle of Corynebacterium glutamicum, the cAMP-dependent
      regulator GlxR and the regulators of acetate metabolism RamA and RamB were
      enriched by DNA affinity chromatography with the promoter region of the sdhCAB
      operon encoding succinate dehydrogenase. The binding of purified GlxR, RamA and
      RamB was verified by electrophoretic mobility shift assays and the regulatory
      effects of these proteins on sdhCAB gene expression were tested by promoter
      activity assays and SDH activity measurements. Evidence was obtained that GlxR
      functions as a repressor and RamA as an activator of sdhCAB expression, whereas
      RamB had no obvious influence under the conditions tested.

PMID- 19583989
TI  - Neuroanatomical characterization of endogenous opioids in the bed nucleus of the
      stria terminalis.
AB  - Numerous neuroanatomical data indicate that the bed nucleus of the stria
      terminalis (BST) provides an interface between cortical and amygdaloid neurons,
      and effector neurons modulating motor, autonomic and neuroendocrine responses.
      Distinct divisions of the BST may be involved in stress response, homeostatic
      regulation, nociception, and motivated behaviors. Endogenous opioid peptides and
      receptors are expressed in the BST, but their exact distribution is poorly
      characterized. The present study used in situ hybridization in order to
      characterize the endogenous opioid system of the BST, focusing on both enkephalin
      and dynorphin neuropeptides, as well as their respective receptors (mu, delta,
      and kappa opioid receptors). We report that preprodynorphin mRNA is observed in
      distinct nuclei of the BST, namely the fusiform, oval and anterior lateral
      nuclei. In contrast, there is a widespread expression of preproenkephalin mRNA in
      both anterior and posterior divisions of the BST. Similarly, mu and kappa opioid
      receptors are broadly expressed in the BST, whereas delta opioid receptor mRNA
      was observed only in the principal nucleus. For further characterization of
      enkephalin-expressing neurons of the BST, we performed a double fluorescent in
      situ hybridization in order to reveal the coexpression of enkephalin peptides and
      markers of GABAergic and glutamatergic neurons. Although most neurons of the BST
      are GABAergic, there is also a modest population of glutamatergic cells
      expressing vesicular glutamate transporter 2 (VGLUT2) in specific nuclei of the
      BST. Finally, we identified a previously unreported population of enkephalinergic
      neurons expressing VGLUT2, which is principally located in the posterior BST.

PMID- 19583990
TI  - Safety assessment of Lactobacillus brevis KB290 as a probiotic strain.
AB  - Lactobacillus brevis KB290 (KB290), a plant-derived probiotic lactic acid
      bacterium, reportedly improves gut health and stimulates immune function. Here we
      extensively investigated the geno-, acute, subacute, and subchronic toxicity of
      KB290 and its bacterial translocation potential. KB290 was non-mutagenic in the
      bacterial reverse mutation assay by the preincubation method. In the single oral
      dose toxicity test, KB290 at 10(9) cfu/ml was nontoxic at maximum capacity (20
      ml/kg). When 10(8), 10(9), or 10(10) cfu/kg was administered daily to rats by
      gavage for 2 weeks (subacute assay), we observed no clear treatment-related
      effect and no evidence of bacterial translocation from the gastrointestinal
      tract. When it was administered for 13 weeks (subchronic assay), we again
      observed no clear treatment-related effect and no significant toxicological
      effect. Based on those results, we consider 10(10) cfu/kg per day, the highest
      dose tested, to be the no observed adverse effect level (NOAEL). These results
      suggest that KB290 is safe for human consumption.

PMID- 19583991
TI  - Comparative hepatotoxicity and clastogenicity of sodium arsenite and three
      petroleum products in experimental Swiss Albino Mice: the modulatory effects of
      Aloe vera gel.
AB  - Petroleum products (PPs) consist of complex chemical mixtures, mainly
      hydrocarbons. Their composition varies considerably with source and use.
      Inappropriate manual handling and use of PPs, in countries like Nigeria, results
      in excessive skin contact with the possibility of hazard to health. There has
      been inadequate evidence to classify diesel, kerosene and hydraulic oil as human
      carcinogens and there is limited evidence for their toxicity and carcinogenicity
      in experimental animals. We compared the hepatotoxicity and clastogenicity of
      diesel, petrol or hydraulic oil with that of sodium arsenite (Na(2)AsO(2)) in
      mice. Our findings showed that these PPs are capable of inducing gamma-glutamyl
      transferase (gammaGT) activity in the serum and liver to levels comparable with
      that induced by Na(2)AsO(2). Mice treated with individual PPs have elevated mean
      liver and serum gammaGT at levels that are significantly different from the
      values observed for the negative control group. Also, the individual PPs alone
      have micronuclei formation induction activity similar to Na(2)AsO(2). We found
      that treatment with Aloe vera gel before the PPs significantly reduced mean liver
      and serum gammaGT, and the mean number of micronuclei scored when compared with
      groups administered each of the PPs alone, supporting the presence of
      hepatoprotective components in Aloe vera.

PMID- 19583992
TI  - Ictal hallucination and hemispheric specialization: findings from 217 cases with
      a unilateral epileptic focus.
AB  - Epileptic populations are generally considered inappropriate to investigate
      hemispheric specialization. However, (1) because hallucination occurs in the
      early stage of the ictus during which activation is observed in and around the
      focus, the former could be a direct result of the latter (hypothesis 1), and (2)
      the type of psychological content of ictal hallucination could depend on which
      hemisphere is ictally activated (hypothesis 2). It was predicted that, on the
      basis of quantitative analysis of previously published singles case reports,
      unilateral ictal hallucinations should occur in the visual field, ear or hemibody
      contralateral to the side of the ictal focus (test of hypothesis 1). It was also
      predicted that verbal ictal auditory hallucinations should result more often from
      left hemisphere foci, and non-verbal auditory ictal hallucinations from right
      hemisphere foci (test of hypothesis 2). Previously published cases (N=217) of
      ictal hallucination from a unilateral epileptic focus were reviewed and analyzed
      with multivariate statistics. Both predictions were strongly supported.

PMID- 19583993
TI  - Predicting protein subnuclear localization using GO-amino-acid composition
      features.
AB  - The nucleus guides life processes of cells. Many of the nuclear proteins
      participating in the life processes tend to concentrate on subnuclear
      compartments. The subnuclear localization of nuclear proteins is hence important
      for deeply understanding the construction and functions of the nucleus. Recently,
      Gene Ontology (GO) annotation has been used for prediction of subnuclear
      localization. However, the effective use of GO terms in solving sequence-based
      prediction problems remains challenging, especially when query protein sequences
      have no accession number or annotated GO term. This study obtains homologies of
      query proteins with known accession numbers using BLAST to retrieve GO terms for
      sequence-based subnuclear localization prediction. A prediction method PGAC,
      which involves mining informative GO terms associated with amino acid composition
      features, is proposed to design a support vector machine-based classifier. PGAC
      yields 55 informative GO terms with training and test accuracies of 85.7% and
      76.3%, respectively, using a data set SNL_35 (561 proteins in 9 localizations)
      with 35% sequence identity. Upon comparison with Nuc-PLoc, which combines
      amphiphilic pseudo amino acid composition of a protein with its position-specific
      scoring matrix, PGAC using the data set SNL_80 yields a leave-one-out cross
      validation accuracy of 81.1%, which is better than that of Nuc-PLoc, 67.4%.
      Experimental results show that the set of informative GO terms are effective
      features for protein subnuclear localization. The prediction server based on PGAC
      has been implemented at http://iclab.life.nctu.edu.tw/prolocgac.

PMID- 19583996
TI  - Load affects human odometry for travelled distance but not straight-line
      distance.
AB  - In a simple homing task with human participants, we disassociated the outbound
      distance travelled from the straight-line distance between home and target. Prior
      to the outbound journey, which involved a detour, participants were given one of
      two instructions concerning the inbound journey, which did not involve a detour:
      to walk the distance travelled or to walk to home. The inbound journey under each
      intention, made with eyes closed at a self-selected pace, was the measure of the
      perceived distance. We conducted two experiments that differed in whether or not
      the detour and target were visible during the outbound journey. In both
      experiments, we manipulated the load carried in the outbound journey (0% or 20%
      body weight) and the speed (fast or slow) of the outbound journey. The outcome of
      both experiments was that, indifferent to speed, participants perceived the
      distance travelled with load to be longer than that travelled without load, but
      perceived home's straight-line distance from target to be the same for both load
      conditions. Perceptions of travel distance and straight-line distance seem to be
      based on different information kinds and to refer to different animal-environment
      relations. In identifying neural mechanisms supportive of navigation, straight
      line distance versus travelled distance may prove to be a productive distinction.

PMID- 19583995
TI  - Differential response of Leydig cells in expressing 11beta-HSD type I and
      cytochrome P450 aromatase in male rats subjected to corticosterone deficiency.
AB  - Emerging evidence suggests that the glucocorticoid and estradiol are important
      for Leydig cell steroidogenesis and are regulated via aromatase for estradiol
      production and 11beta-HSD for oxidatively inactivating glucocorticoid. Although
      it is known that corticosterone deficiency impaired Leydig cell steroidogenesis,
      its effect on the expression of Leydig cell 11beta-HSD type I and aromatase are
      yet to be recognized. Following metyrapone-induced corticosterone deficiency,
      serum corticosterone and testosterone levels decrease, whereas serum estradiol
      remains unaltered. 11beta-HSD type I mRNA and its activity was decreased by
      corticosterone deficiency, whereas the activity and mRNA of aromatase remains
      unaltered. Simultaneous administration of corticosterone prevented its deficiency
      induced changes of 11beta-HSD type I in Leydig cells. Our results show that
      metyrapone-induced corticosterone deficiency impairs Leydig cell 11beta-HSD
      enzyme activity and 11beta-HSD type I mRNA expression, and the Leydig cells need
      to maintain their intracellular concentration of corticosterone for a normal
      function.

PMID- 19583994
TI  - IL-6 augments angiotensinogen in primary cultured renal proximal tubular cells.
AB  - In human kidneys, the mechanisms underlying angiotensinogen (AGT) augmentation by
      interleukin 6 (IL-6) are poorly understood and the only information available is
      in HK-2, immortalized human renal proximal tubular epithelial cells. Therefore,
      the present study was performed to elucidate the effects of IL-6 on AGT
      expression in primary cultured human renal proximal tubular epithelial cells
      (RPTEC) after characterization of HK-2 and RPTEC. RPTEC showed low basal AGT mRNA
      (11+/-1%) and protein (7.0+/-0.9%) expression, high IL-6 receptor (IL-6R)
      expression (282+/-17%), and low basal NF-kappaB (43+/-7%) and STAT3 (43+/-7%)
      activities compared to those in HK-2. In RPTEC, AGT mRNA and protein expressions
      were enhanced by IL-6 (172+/-31% and 378+/-39%, respectively). This AGT
      augmentation was attenuated by an IL-6R antibody. STAT3 phosphorylation (366+/
      55% at 30min) and translocation were enhanced by IL-6. The AGT augmentation was
      attenuated by a STAT3 inhibitor. These data indicate that IL-6 increases AGT
      expression via STAT3 pathway in RPTEC.

PMID- 19583997
TI  - Transcriptional regulation of iNOS and COX-2 by a novel compound from Curcuma
      comosa in lipopolysaccharide-induced microglial activation.
AB  - Overproduction of pro-inflammatory mediators resulting from chronic activation of
      microglia has been implicated in many neurodegenerative disorders, such as
      Parkinson's disease and Alzheimer's disease. In this study, we investigated the
      effects of (3R) 1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, or compound 049 on the
      production of pro-inflammatory mediators in lipopolysaccharide (LPS)-treated
      microglia. Compound 049 is a pure compound fractionated from the hexane extract
      of Curcuma comosa, an indigenous plant of Thailand traditionally used as an anti
      inflammatory agent for the treatment of uterine inflammation. It was found that
      pretreatment of the highly aggressively proliferating immortalized (HAPI), rat
      microglial cell line, with compound 049, at the concentrations of 0.1, 0.5 and
      1microM significantly decreased LPS-induced NO and PGE(2) production in a
      concentration-dependent manner. Parallel to the decreases in NO and PGE(2)
      production was a reduction in the expression of inducible NO synthase (iNOS) and
      cyclooxygenase 2 (COX-2) as measured by mRNA and protein levels. These results
      indicate that compound 049 possesses an anti-inflammatory activity and may have a
      therapeutic potential for the treatment of neurodegenerative diseases related to
      microglial activation.

PMID- 19583998
TI  - Application of chitosan microspheres for nasal delivery of vaccines.
AB  - Nasal vaccines offer several benefits, such as highly vascular mucous membranes,
      low enzymatic degradation compared to oral vaccines, and greater acceptability to
      patients. Nasal vaccines, however, have to overcome several limitations,
      including mucociliary clearance and the inefficient uptake of soluble antigens.
      Therefore, nasal vaccines require potent adjuvants and delivery systems to
      enhance their immunogenicity and to protect their antigens. Chitosan is a cheap,
      biocompatible, biodegradable, mucoadhesive, and nontoxic natural polymer.
      Chitosan microspheres have been investigated to determine whether they allow the
      controlled release of drugs and vaccines. They have figured in various studies on
      the vaccine delivery system through the nasal route. Several researchers have
      developed modified chitosan microspheres through their concomitant use with
      adjuvants or immunomodulators for an additive and a synergistic effect, and
      through the mannosylation of chitosan for receptor-mediated targeting antigen
      presenting cells. The results of the recent researches on chitosan microspheres
      used as a nasal vaccine delivery system are discussed in this review.

PMID- 19583999
TI  - Coexpression of omega subunit in E. coli is required for the maintenance of
      enzymatic activity of Xanthomonas campestris pv. campestris RNA polymerase.
AB  - In this study, plasmid pBBad22K was modulated to be able to coexpress the
      subunits of Xanthomonascampestris pv. campestris (Xcc) core RNA polymerase (RNAP)
      in an Escherichia coli host. The subunit-encoding genes of Xcc core RNAP were PCR
      amplified respectively to convert into gene cassettes in which an intact subunit
      encoding gene and a ribosome binding site (RBS) preceding the gene were
      contained, and were then cloned one by one into pBBad22K. In addition, a
      hexahistidine tag (His-tag) was introduced into the C-terminus of alpha subunit
      encoded rpoA during PCR for facilitating purification of Xcc core RNAP. The
      resultant vectors, pBC-CBA and pBC-CBAZ, were used for overproduction of Xcc core
      RNAP lacking or containing omega, respectively. The assembly of Xcc core RNAP
      subunits that were coexpressed from these vectors was demonstrated after
      purification via two-step column chromatography. The yield of Xcc core RNAP
      containing omega had a 67% increase compared with that of one lacking omega,
      indicating that omega promotes the assembly of Xcc core RNAP. In addition, Xcc
      core RNAP lacking omega showed a 13-fold decrease in enzymatic activity in
      comparison with that containing omega. Promoter-specific transcription assays by
      recombinant Xcc core RNAP reconstituted with external added sigma factor showed
      that the absence of omega debilitates the transcriptional activity of Xcc RNAP.
      Our results demonstrated that omega is not only capable of strengthening the
      stability, but is also required for the maintenance of enzymatic activity of Xcc
      RNAP.

PMID- 19584000
TI  - Ustilago maydis accumulates beta-carotene at levels determined by a retinal
      forming carotenoid oxygenase.
AB  - The basidiomycete Ustilago maydis, the causative agent of corn smut disease, has
      emerged as a model organism for dimorphism and fungal phytopathogenicity. In this
      work, we line out the key conserved enzymes for beta-carotene biosynthesis
      encoded by the U. maydis genome and show that this biotrophic fungus accumulates
      beta-carotene. The amount of this pigment depended on culture pH and aeration but
      was not affected by light and was not increased by oxidative stress. Moreover, we
      identified the U. maydis gene, cco1, encoding a putative beta-carotene cleavage
      oxygenase. Heterologous overexpression and in vitro analyses of purified enzyme
      demonstrated that Cco1 catalyzes the symmetrical cleavage of beta-carotene to
      yield two molecules of retinal. Analyses of beta-carotene and retinal contents in
      U. maydiscco1 deletion and over-expression strains confirmed the enzymatic
      function of Cco1, and revealed that Cco1 determines the beta-carotene content.
      Our data indicate that carotenoid biosynthesis in U. maydis is carried out to
      provide retinal rather than to deliver protective pigments. The U. maydis genome
      also encodes three potential opsins, a family of photoactive proteins that use
      retinal as chromophore. Two opsin genes showed different light-regulated
      expression patterns, suggesting specialized roles in photobiology, while no mRNA
      was detected for the third opsin gene in the same experiments. However, deletion
      of the cco1 gene, which should abolish function of all the retinal-dependent
      opsins, did not affect growth, morphology or pathogenicity, suggesting that
      retinal and opsin proteins play no relevant role in U. maydis under the tested
      conditions.

PMID- 19584001
TI  - Role of nitric oxide in obsessive-compulsive behavior and its involvement in the
      anti-compulsive effect of paroxetine in mice.
AB  - In view of the reports that nitric oxide modulates the neurotransmitters
      implicated in obsessive-compulsive disorder, patients with obsessive-compulsive
      disorder exhibit higher plasma nitrate levels, and drugs useful in obsessive
      compulsive disorder influence nitric oxide, we hypothesized that nitric oxide may
      have some role in obsessive-compulsive behavior. We used marble-burying behavior
      of mice as the animal model of obsessive-compulsive disorder, and nitric oxide
      levels in brain homogenate were measured using amperometric nitric oxide
      selective sensor method. Intraperitoneal administration of nitric oxide enhancers
      viz. nitric oxide precursor-l-arginine (800 mg/kg), nitric oxide donor-sodium
      nitroprusside (3 mg/kg) or phosphodiesterase type 5 inhibitor-sildenafil (3
      mg/kg) significantly increased marble-burying behavior as well as brain nitrites
      levels, whereas treatment with 7-nitroindazole-neuronal nitric oxide synthase
      inhibitor (20-40 mg/kg, i.p.) or paroxetine-selective serotonin reuptake
      inhibitor (5-10 mg/kg, i.p.) dose dependently attenuated marble-burying behavior
      and nitrites levels in brain. Further, co-administration of sub-effective doses
      of 7-nitroindazole (10 mg/kg) and paroxetine (2.5 mg/kg) significantly attenuated
      marble-burying behavior. Moreover, pretreatment with l-arginine (400 mg/kg,
      i.p.), sodium nitroprusside (2.0 mg/kg, i.p.) or sildenafil (2.0 mg/kg, i.p.)
      significantly attenuated the inhibitory influence of 7-nitroindazole (40 mg/kg)
      or paroxetine (10 mg/kg) on marble-burying behavior as well as on brain nitrites
      levels. None of the above treatment had any significant influence on locomotor
      activity. In conclusion, obsessive compulsive behavior in mice appears related to
      nitric oxide in brain, and anti-compulsive effect of paroxetine appears to be
      related to decrease central levels of nitric oxide.

PMID- 19584002
TI  - Ontogenetic development of erythropoiesis can be studied non-invasively in GATA
      1:DsRed transgenic zebrafish.
AB  - For the erythroid cell lineage development in vertebrates, GATA-1 transcription
      factor is essential. In our report, we have demonstrated that the approximate
      developmental status of erythrocytes and the progression of blood formation can
      be studied non-invasively in GATA-1:DsRed transgenic zebrafish (Danio rerio)
      embryo and larva by characterization of fluorescence luminance spectra. The study
      was carried out for animals maintained under normoxic and hypoxic (152 and 20
      torr PO(2) respectively) conditions up to 10 days post-fertilization (dpf) and
      total blood cell concentrations and fluorescent cells' percentage were determined
      for this purpose. The erythroids were classified into five intensity stages (IS)
      on the basis of their fluorescence intensity. The luminescent cells with medium
      intensities (IS3) in normoxic animals were found throughout 2 to 10 dpf although
      in lower quantity while in hypoxic group they appeared from 5 dpf to 10 dpf
      showing a maximum of 15% of the total luminescent cells at 8 dpf. The total blood
      cell concentration dropped after 8 dpf in contrast to hypoxic group which showed
      further increasing trend. The fluorescent cells' percentage in normoxic group was
      generally higher as compared to the hypoxic ones. Our method successfully defined
      various stages of erythroid development. An effort was also made to correlate our
      luminance data (GATA-1 expression) and total blood cell concentrations with Epo
      mRNA production. Quantitative RT-PCR of 2-15 dpf old zebrafish was carried out
      for this purpose. Normoxic animals showed 1-3 Epo mRNA copies per ng RNA in
      contrast to the hypoxic larvae that showed remarkable fluctuation of 1 to 12 Epo
      mRNA copies per ng RNA during development. The blood volume (aortic diameter) and
      production time scale proved to be important factors to define the relationship
      of Epo mRNA with total blood cell concentration and GATA-1 protein expression
      respectively.

PMID- 19584004
TI  - Biotech acquisitions by big pharma: why and what is next.
AB  - Leading pharmaceutical companies are increasingly making biotech acquisitions to
      help them refill their pipelines, but what makes a good acquisition target and
      what will be the impact of the present financial crisis on deals.

PMID- 19584003
TI  - Application of a double-reporter-guided mutant selection method to improve
      clavulanic acid production in Streptomyces clavuligerus.
AB  - A reporter-guided mutant selection (RGMS) method has been developed wherein
      reporters are used to facilitate selection of target over-expressing mutants. It
      was applied to improve clavulanic acid (CA) production in Streptomyces
      clavuligerus. In a single-reporter design, the transcriptional activator ccaR of
      CA biosynthesis was chosen as the over-expressing target, and neo (resistance to
      kanamycin) as the reporter; 51% of the selected mutants produced higher CA titer
      than the starting strain. To reduce the high false positive rate of single
      reporter method, a double-reporter RGMS vector was configured, in which an xylE
      neo double-reporter cassette was used to monitor ccaR expression; 90% of mutants
      selected by the modified method showed improvement in CA titer. Double-reporter
      RGMS is the most efficient tool for mutant selection reported to date and is also
      an alternative method for target over-expression. The mutants obtained by RGMS
      showed great genetic diversity that could be further exploited in inverse
      metabolic engineering.

PMID- 19584007
TI  - [Medial pancreatectomy ].

PMID- 19584005
TI  - The interactions of iron with other divalent metals in the intestinal tract of a
      freshwater teleost, rainbow trout (Oncorhynchusmykiss).
AB  - This study examined the concentration-dependent interactive effects of four
      essential (Cu(2+), Zn(2+), Ni(2+), Co(2+)) and two non-essential (Pb(2+) and
      Cd(2+)) divalent metals on intestinal iron (Fe(2+)) absorption in freshwater
      rainbow trout (Oncorhynchusmykiss) using an invitro gut sac technique. All of the
      divalent metals except cobalt inhibited the intestinal Fe(2+) absorption in fish,
      and the magnitude of inhibition followed the order of:
      Ni(2+)~Pb(2+)>Cd(2+)~Cu(2+)>Zn(2+). The mucosal epithelium of the intestine was
      found to be the most sensitive to inhibition relative to the mucus or blood
      compartment, suggesting that these interactions likely occur via the divalent
      metal transporter-1 (DMT1). In addition, the reciprocal effects of Fe(2+) on
      intestinal accumulation of lead and cadmium were investigated. Elevated Fe(2+)
      did not affect lead accumulation in the intestine, indicating a greater affinity
      of Pb(2+) to the Fe(2+) transport pathway and/or the existence of additional
      pathways for lead absorption. In contrast, the accumulation of cadmium in the
      intestine decreased considerably in the presence of excess Fe(2+), indicating the
      importance of the Fe(2+) absorption pathway in dietary cadmium accumulation in
      fish. Overall, our study provides important insights into the mechanisms of
      dietary uptake of several divalent metals in freshwater fish.

PMID- 19584006
TI  - Population genetics of the mosquito Culex pipiens pallens reveals sex-linked
      asymmetric introgression by Culex quinquefasciatus.
AB  - The Culex pipiens complex in Asia includes a temperate subspecies, Culex pipiens
      pallens, of uncertain taxonomic status. The shape of the male genitalia suggests
      it is a hybrid between Cx. pipiens and Cx. quinquefasciatus. We studied
      populations of Cx. p. pallens in Japan, Korea, and China and compared them to
      local populations of Cx. quinquefasciatus and Cx. p. pipiens. We examined
      variation in a nuclear intron in the acetylcholinesterase-2 gene [ACE] and eight
      microsatellite loci. We found a distinct microsatellite signature for Cx. p.
      pallens indicating restricted gene flow between Eastern and Western populations
      of Cx. pipiens, supporting the existence of two subspecies. Furthermore, a
      multilocus genotype analysis revealed current hybridization between Cx. p.
      pallens and Cx. quinquefasciatus in southern Japan, Republic of Korea, and China
      but not in Hokkaido, in northern Japan. Surprisingly, however, we found that the
      sex-linked ACE locus in chromosome I has introgressed asymmetrically through the
      males such that all male Cx. p. pallens have a copy of the Cx. quinquefasciatus
      ACE locus. This result highlights some of the potential consequences of
      hybridization between local and introduced species to disease transmission
      worldwide.

PMID- 19584008
TI  - [Intra-peritoneal laparoscopy for umbilical hernia].

PMID- 19584009
TI  - [Roux-en-Y intrathoracic esopho-jejunal anastomosis after total gastrectomy].

PMID- 19584010
TI  - Cytokinin signaling during root development.
AB  - The cytokinin class of phytohormones regulates division and differentiation of
      plant cells. They are perceived and signaled by a phosphorelay mechanism similar
      to those observed in prokaryotes. Research into the components of phosphorelay
      had previously been marred by genetic redundancy. However, recent studies have
      addressed this with the creation of high-order mutants. In addition, several new
      elements regulating cytokinin signaling have been identified. This has uncovered
      many roles in diverse developmental and physiological processes. In this review,
      we look at these processes specifically in the context of root development. We
      focus on the formation and maintenance of the root apical meristem, primary and
      secondary vascular development, lateral root emergence and development, and root
      nodulation. We believe that the root is an ideal organ with which to investigate
      cytokinin signaling in a wider context.

PMID- 19584011
TI  - Live-cell imaging in the study of neurodegeneration.
AB  - The development of vital fluorescent synthetic dyes and the generation of a
      myriad of genetically encoded fluorescent proteins permit sensitive visualization
      of a broad range of dynamic features in living cells with fluorescence
      microscopy. Many neurodegenerative diseases such as Alzheimer's disease (AD),
      amyotrophic lateral sclerosis (ALS), Creutzfeld-Jacob disease (CJD), Huntington's
      disease (HD), multiple sclerosis (MS), and Parkinson's disease (PD) share common
      aspects on a cellular level that are associated with a change in the dynamic
      behavior of the whole cell, cell compartments, or single proteins. These include
      disturbances of transport mechanisms or protein turnover, missorting and
      aggregation of proteins, and changes in the structural plasticity of neurons. In
      this chapter, we describe different live-cell-imaging techniques, present
      representative examples, and discuss the current and potentially future use of
      live-cell-imaging approaches to answer key questions regarding the mechanisms or
      potential treatments of neurodegenerative diseases.

PMID- 19584012
TI  - Interactions between heparan sulfate and proteins-design and functional
      implications.
AB  - Heparan sulfate (HS) proteoglycans at cell surfaces and in the extracellular
      matrix of most animal tissues are essential in development and homeostasis, and
      variously implicated in disease processes. Functions of HS polysaccharide chains
      depend on ionic interactions with a variety of proteins including growth factors
      and their receptors. Negatively charged sulfate and carboxylate groups are
      arranged in various types of domains, generated through strictly regulated
      biosynthetic reactions and with enormous potential for structural variability.
      The level of specificity of HS-protein interactions is assessed through binding
      experiments in vitro using saccharides of defined composition, signaling assays
      in cell culture, and targeted disruption of genes for biosynthetic enzymes
      followed by phenotype analysis. While some protein ligands appear to require
      strictly defined HS structure, others bind to variable saccharide domains without
      any apparent dependence on distinct saccharide sequence. These findings raise
      intriguing questions concerning the functional significance of regulation in HS
      biosynthesis.

PMID- 19584013
TI  - Fibroblasts-a diverse population at the center of it all.
AB  - The capacity of fibroblasts to produce and organize the extracellular matrix and
      to communicate with other cells makes them a central component of tissue biology.
      Even so, fibroblasts remain a somewhat enigmatic population. Our inability to
      fully comprehend these cells is in large part due to the paucity of unique
      cellular markers and to their pervasive diversity. Much of our understanding of
      fibroblast diversity has evolved from studies where subpopulations of these cells
      have been produced without resorting to cell surface markers. In this regard,
      cloning and mechanical separation of tissues prior to establishing cultures has
      provided multiple subpopulations. Nonetheless, in isolated situations, the
      expression or lack of expression of Thy-1/CD90 has been used to separate
      fibroblast subsets. The role of fibroblasts in intercellular communication is
      emerging through the implementation of organotypic studies in which three
      dimensional fibroblast culture are combined with other populations of cells. Such
      studies have revealed critical paracrine loops that are essential for organ
      development and for wound repair. These studies also provide a backdrop for the
      emerging field of tissue engineering. The participation of fibroblasts in the
      regulation of tissue homeostasis and their contribution to the aging process are
      emerging issues that require better understanding. In short, fibroblasts
      represent a multifaceted, complex group of cells.

PMID- 19584014
TI  - Imprinting and extraembryonic tissues-mom takes control.
AB  - Genomic imprinting is an epigenetic mechanism that silences one parental allele
      of a small subset of genes. Many imprinted genes exhibit this property only in
      extraembryonic tissues-placenta and yolk sac. This has led to the idea that
      imprinting in mammals coevolved with some aspect of placentation. Nevertheless,
      many studies of imprinting have ignored the extraembryonic tissues, the yolk sac
      and its precursor, the primitive endoderm, in particular. The primitive endoderm
      is involved in very early signaling events during a critical stage in
      development, gastrulation, during which body plan axes and head process
      neuroectoderm are established. Improper signaling from primitive endoderm as a
      result of abnormal expression of imprinted genes has the capacity to effect long
      term defects in embryonic/fetal tissues that might hitherto have been overlooked.
      We discuss these gaps in the knowledge, propose a mechanism for genomic
      imprinting based on current data, and suggest a line of investigation that will
      expand our understanding of this unique regulatory mechanism and its impact on
      development.

PMID- 19584015
TI  - Cell and molecular biology of ATP-binding cassette proteins in plants.
AB  - ATP-binding cassette (ABC) proteins constitute a large and diverse superfamily of
      membrane-bound and soluble proteins, which are involved in a wide range of
      biological processes in all organisms from prokaryotes to eukaryotes. Genome
      analyses of model plants, for example, Arabidopsis and rice, have revealed that
      plants have more than double numbers of this family member in their genomes
      compared to animals and insects. In recent years, various biochemical and
      physiological functions of ABC proteins in plants have been reported. Some are
      relevant for the defense mechanisms to biotic and abiotic stresses, whereas
      others are involved in the basic functions necessary for maintaining the plant
      life. Here, we provide an updated inventory of plant ABC proteins and summarize
      their tissue specificities, membrane localizations, and physiological functions.

PMID- 19584016
TI  - Cell and molecular biology of the fastest myosins.
AB  - Chara myosin is a class XI plant myosin in green algae Chara corallina and
      responsible for fast cytoplasmic streaming. The Chara myosin exhibits the fastest
      sliding movement of F-actin at 60 mum/s as observed so far, 10-fold of the
      shortening speed of muscle. It has some distinct properties differing from those
      of muscle myosin. Although knowledge about Chara myosin is very limited at
      present, we have tried to elucidate functional bases of its characteristics by
      comparing with those of other myosins. In particular, we have built the putative
      atomic model of Chara myosin by using the homology-based modeling system and
      databases. Based on the putative structure of Chara myosin obtained, we have
      analyzed the relationship between structure and function of Chara myosin to
      understand its distinct properties from various aspects by referring to the
      accumulated knowledge on mechanochemical and structural properties of other
      classes of myosin, particularly animal and fungal myosin V. We will also discuss
      the functional significance of Chara myosin in a living cell.

PMID- 19584017
TI  - Removal of either N-glycan site from the envelope receptor binding domain of
      Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor
      usage.
AB  - Three N-linked glycosylation sites were removed from the envelope glycoproteins
      of Friend, Moloney, and AKV mouse ecotropic gammaretroviruses: gs1 and gs2, in
      the receptor binding domain; and gs8, in a region implicated in post-binding cell
      fusion. Mutants were tested for their ability to infect rodent cells expressing 4
      CAT-1 receptor variants. Three mutants (Mo-gs1, Mo-gs2, and Fr-gs1) infect NIH
      3T3 and rat XC cells, but are severely restricted in Mus dunni cells and Lec8, a
      Chinese hamster cell line susceptible to ecotropic virus. This restriction is
      reproduced in ferret cells expressing M. dunni dCAT-1, but not in cells
      expressing NIH 3T3 mCAT-1. Virus binding assays, pseudotype assays, and the use
      of glycosylation inhibitors further suggest that restriction is primarily due to
      receptor polymorphism and, in M. dunni cells, to glycosylation of cellular
      proteins. Virus envelope glycan size or type does not affect infectivity. Thus,
      host range variation due to N-glycan deletion is receptor variant-specific, cell
      specific, virus type-specific, and glycan site-specific.

PMID- 19584018
TI  - Human antibody titers to Epstein-Barr Virus (EBV) gp350 correlate with
      neutralization of infectivity better than antibody titers to EBV gp42 using a
      rapid flow cytometry-based EBV neutralization assay.
AB  - Measurement of neutralizing antibodies to Epstein-Barr virus (EBV) is important
      for evaluation of candidate vaccines. The current neutralization assay is based
      on antibody inhibition of EBV transformation of B cells and requires 6 weeks to
      perform. We developed a rapid, quantitative flow cytometry assay and show that
      neutralizing antibody titers measured by the new assay strongly correlate with
      antibody titers in the standard transformation-based assay. Antibodies to EBV
      gp350 and gp42 have been shown to block infection of B cells by EBV. Using new
      assays to quantify antibodies to these glycoproteins, we show for the first time
      that human plasma contains high titers of antibody to gp42; these titers
      correlate with neutralization of EBV infectivity or transformation. Furthermore,
      we show that antibody titers to EBV gp350 correlate more strongly with
      neutralization than antibody titers to gp42. These assays should be useful in
      accessing antibody responses to candidate EBV vaccines.

PMID- 19584019
TI  - Delineating the psychic structure of substance abuse and addictions: should
      anxiety, mood and impulse-control dysregulation be included?
AB  - Current "official" nosology (e.g. DSM IV) is largely limited to physical
      manifestations of addiction that can be objectively observed and are suited to
      the maintaining of an "atheoretical" perspective. However, addicted subjects
      display additional psychiatric symptoms that affect their well-being and social
      functioning and, in accordance with DSM IV, are typically relegated to the domain
      of psychiatric "comorbidity." We contend that the relationship of these
      psychiatric symptoms with addiction is very close, as demonstrated by the high
      frequency of association observed. We further assert that substance use may
      modify pre-existing psychic structures such as temperament and related
      subthreshold conditions and lead to addiction as a specific mental disorder,
      inclusive also of symptoms pertaining to mood/anxiety, or impulse-control
      dimensions. The present contribution addresses the weaknesses of the current DSM
      based nosology of addiction-related mental comorbidity. We highlight the overlap
      of the biological substrates and the neurophysiology of addictive processes and
      psychiatric symptoms associated with addiction, and propose the inclusion of
      specific mood, anxiety, and impulse-control dimensions in the psychopathology of
      addictive processes. We postulate that addiction reaches beyond the mere result
      of drug-elicited effects on the brain and cannot be peremptorily equated only
      with the use of drugs despite the adverse consequences produced. We infer that
      mood, anxiety and impulse-control dysregulation is at the very core of both the
      origins and clinical manifestations of addiction and should be incorporated into
      the nosology of the same, emphasising how addiction is a relapsing chronic
      condition in which psychiatric manifestations play a crucial role. To conclude,
      addictionology cannot be severed from its psychopathological connotations, in
      view of the undeniable presence of symptoms, of their manifest contribution to
      the way addicted patients feel and behave, and to the role they play in
      maintaining the continued use of substances.

PMID- 19584020
TI  - Cognitive reactivity: investigation of a potentially treatable marker of suicide
      risk in depression.
AB  - BACKGROUND: Suicidal ideation is the most stable symptom of depression across
      episodes. This relative stability may be brought about by increased cognitive
      reactivity to sad mood (CR) during periods of remission. The idea is that a
      network of depressive cognitions, which include suicidal ideation, becomes
      strengthened with each episode of depression. Consequently, the whole network may
      be more easily re-activated, for instance by an episode of low mood. We examined
      the association between reactivity of suicidal cognitions during recovery and the
      presence of suicidal ideation and behavior during the previous depressive
      episode. METHODS: In a case-control design, the CR profiles of recovered
      depressed participants with (N=355) and without (N=250) a history of suicidal
      ideation were compared. Structured clinical interviews were used to determine
      diagnoses and prior symptoms. Cognitive reactivity profile was measured with the
      Leiden Index of Depression Sensitivity-Revised (LEIDS-R). RESULTS: Suicidal
      ideation during a depressive episode was associated with a distinct CR profile
      during remission: elevated hopelessness reactivity scores. This relationship
      between prior suicidality and current CR was independent of anxiety disorder
      comorbidity. Moreover, a history of suicide attempt(s) was also associated with a
      distinct CR profile. These individuals had both higher hopelessness reactivity
      and higher aggression reactivity than the non-suicidal and suicidal ideation
      groups. LIMITATIONS: Symptoms during the previous depressive episode were
      assessed retrospectively. CONCLUSIONS: This is the first study to show that CR
      may underlie the relative stability of suicidal symptoms independent of anxiety
      comorbidity and that suicidal ideation and suicidal behavior are associated with
      distinct patterns of CR. Since CR is a potentially treatable vulnerability marker
      of depression recurrence, this has important clinical implications.

PMID- 19584021
TI  - Symptoms of depression and anxiety mediate the relationship between self-esteem
      and paranoia.

PMID- 19584022
TI  - Chronic fluoxetine differentially modulates the hippocampal microtubular and
      serotonergic system in grouped and isolation reared rats.
AB  - Social isolation from weaning in rats produces behavioural and hippocampal
      structural changes at adulthood. Here, rats were group or isolation reared for
      eight-weeks. Following the initial four-week period of rearing, fluoxetine (10
      mg/kg i.p.) was administered for 28 days. Changes in recognition memory,
      hippocampal monoamines, and cytoskeletal microtubules were investigated.
      Isolation-rearing for four- or eight-weeks produced recognition memory deficits
      that were not reversed by fluoxetine. Eight-weeks of isolation decreased alpha
      tubulin acetylation (Acet-Tub) and the tyrosinated/detyrosinated alpha-tubulin
      ratio (Tyr/Glu-Tub), suggesting major alterations in microtubule dynamics and
      neuronal plasticity. In grouped rats, fluoxetine decreased Acet-Tub without
      changes in Tyr/Glu-Tub. In isolates, fluoxetine did not affect Acet-Tub but
      increased Tyr/Glu-Tub. Finally, fluoxetine altered serotonin metabolism in
      grouped, but not in isolated animals. Therefore, isolation-rearing changes the
      hippocampal responses of the serotonergic and microtubular system to fluoxetine.
      These findings show that early-life experience induces behavioural changes
      paralleled by alterations in cytoskeletal and neurochemical functions.

PMID- 19584023
TI  - Carnosine attenuates oxidative stress and apoptosis in transient cerebral
      ischemia in rats.
AB  - Cerebral ischemia leads to cognitive decline and neuronal damage in the
      hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal
      loss after cerebral ischemia and reperfusion injury. Carnosine has both
      antioxidant and neuroprotective effects against ROS. In the present study, the
      effects of carnosine on oxidative stress, apoptotic neuronal cell death and
      spatial memory following transient cerebral ischemia in rats were investigated.
      Transient ischemia was induced by occlusion of right common carotid artery of
      rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal
      injection of 250 mg/kg carnosine or saline 30 min prior to experiment.
      Determination of antioxidant enzyme activities was performed
      spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed
      using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a
      significant decrease in lipid peroxidation and increase in antioxidant enzyme
      activities in ischemic rat brains. The number of TUNEL-positive cells was
      decreased significantly in carnosine-treated group when compared with the
      ischemia-induction group. Carnosine treatment did not provide significant
      protection from ischemia induced deficits in spatial learning. The results show
      that carnosine is effective as a prophylactic treatment for brain tissue when it
      is administered before ischemia without affecting spatial memory.

PMID- 19584024
TI  - Expression of two metallothionein genes in different brain regions of common
      carp.
AB  - The expression pattern of two metallothionein (MT) genes in response to
      temperature shock and exposure to Cd(2+) was investigated in the brain of common
      carp ( Cyprinus carpio ), in whole-animal experiments. The changes in the levels
      of MT-1 and MT-2 mRNA in the olfactory lobe, midbrain and cerebellum were
      followed by semiquantitative RT-PCR. The inducibility of the two MT genes was
      brain region and stressor-specific. Cd(2+) affected mostly the expression of MT
      2, while the level of the MT-1 transcript did not change significantly in any of
      the brain regions examined. Moreover, the MT-2 expression was regulated
      spatially; MT-2 was induced significantly more strongly in the olfactory lobe
      than in the cerebellum or midbrain. A sudden temperature drop mainly affected the
      expression of the MT-1 gene; after 5 h of cold shock, the MT-1 mRNA level was
      about 25% of the basal value in the cerebellum and the midbrain region. The MT-2
      expression did not change significantly during this treatment.

PMID- 19584025
TI  - Ultrastructural aspects of previtellogenic oocyte growth in hermaphrodite
      sharpsnout seabream, Diplodus puntazzo (Teleostei, Sparidae).
AB  - This paper describes various aspects of previtellogenic oocyte growth in
      sharpsnout seabream, Diplodus puntazzo , is an important marine culture fish
      species in the Mediterranean. The ultrastructural characteristics of nuclear
      morphology, nuclear-cytoplasmic ratio and the starting of the follicle envelope
      formation were described in detail. These cells do not significantly differ from
      those of the other teleost species. The ultrastructural aspects provide new
      information on the reproductive biology of Sparidae.

PMID- 19584026
TI  - Effect of N-metylcarbamate pesticide bendiocarb on cattle lymphocytes after in
      vitro exposure.
AB  - Bendiocarb is a carbamate broad-spectrum insecticide used to control disease
      vectors such as mosquitoes and flies, as well as household and agricultural
      pests. Nowadays, only few papers reporting cytogenetic or possible genotoxic
      effect of this insecticide on mammalian cells are available. In the present study
      24-hour exposure to bendiocarbamate at concentrations ranging from 20 to 160
      MUg/ml was used for investigation of unstable chromosomal aberrations (CA),
      sister chromatid exchanges (SCE) and stable chromosomal aberration induction in
      cultured bovine peripheral lymphocytes. The slight but no significant increase of
      chromatide breaks frequency was observed after the exposure of lymphocytes to 80
      MUg/ml of bendiocarb. At the highest concentration added to the cell cultures
      (160 MUg/ml) mitotic index decrease was shown in both donors (p < 0.05; p <
      0.01). Both statistically significant elevation of SCEs (p < 0.05) and a
      reduction of proliferative indices (PI) (p < 0.01) were shown at a dose of 80
      MUg/ml. By means of two fluorescent-labelled whole chromosome-painting probes,
      stable aberrations such as bovine chromosome 1 and 5 translocation as well as
      numerical aberrations (polyploidies, heteroploidies) were visualised under
      fluorescent microscope in some examined metaphases.

PMID- 19584027
TI  - Genotoxicity study of Hypiran and Chamomilla herbal drugs determined by in vivo
      supervital micronucleus assay with mouse peripheral reticulocytes.
AB  - The growth in popularity of Over The Counter (OTC) of medicinal products or other
      natural sources have taken a very large share of healthcare system therefore it
      is essential to determine their safety as for as public health is concerned.In
      this study Maximum Tolerated Dose (MTD) was obtained according to CSGMT protocol
      presented by the Environmental Mutagen Society of Japan. The positive group
      received mitomycin C in dose of 0.5 mg/kg. The peripheral blood samples before
      treatment (zero time) were considered as negative control. The MTD of Hypiron was
      12 ml/kg and for Chamomilla was 10 ml/kg. Doses of MTD, 1/2 MTD and 1/4 MTD were
      considered for test groups. Then blood samples were prepared 48 hours after first
      administration of drugs and kept on precoated Acridine orange slides. The scoring
      of micronucleated reticulocytes were carried out per 2000 counted reticulocytes
      in each slide by fluorescent microscope. The results were statistically analyzed.
      Results of Hypiran were compared with negative control group and the P value was
      P > 0.05, but the p value of Chamomilla was P < 0.05. Also, the p value of
      Hypiran and Chamomilla compared with historical negative control group was less,
      therefore Chamomilla herbal drog can be classified as equivocul category of
      genotoxicity and Hypiran did not show genotoxicity.

PMID- 19584028
TI  - Effect of moderate hypoxia/reoxygenation on mitochondrial adaptation to acute
      severe hypoxia.
AB  - In an experimental model, it was shown that repetitive periods of
      hypoxia/reoxygenation (H/R) [5 cycles of 5 min hypoxia (12% O(2) in N(2) )
      followed by 15 min normoxia, daily for three weeks] attenuated basal and
      stimulated in vitro lipid peroxidation, as well as H(2)O(2) production in liver
      and brain mitochondria of rats exposed to acute severe hypoxia. Adaptation to
      moderate H/R enhanced in mitochondria the production and activity of reactive
      oxygen species scavengers, such as glutathione, manganese superoxide dismutase,
      glutathione peroxidase, and glutathione-S-transferase. It was demonstrated that
      the maintenance of GSH-redox cycle by activation of glutathione reductase and
      NADP(+) -dependent isocitrate dehydrogenase is an integral part of the
      biochemical adaptive mechanism of oxidative tolerance to new damaging factor.
      Brain mitochondria showed more sensitivity to oxidative stress than liver
      mitochondria, and long-lasting sessions of H/R affect differentially their pro
      /antioxidant homeostasis.

PMID- 19584029
TI  - UV-B response of greening barley seedlings.
AB  - The relationship between the greening stage of barley seedlings and their
      response to UV-B irradiation was studied. Etiolated barley seedlings ( Hordeum
      vulgare L., cv. Alfa) greened 12, 24 and 48 h were exposed to UV-B irradiation
      (312 nm) for 5 h. As a result of UV-B treatment the rate of CO(2) fixation and
      chlorophyll contents decreased but flavonoids, UV-B-induced compounds and
      carotenoids increased. The inhibition of photosynthesis in green plants was lower
      in comparison to greening ones. The 12 h greening plants were more sensitive to
      UV-B treatment than the plants greening 24 h and particularly 48 h, estimated by
      the quantum efficiency of PSII photochemistry and the oxygen production rate. The
      levels of flavonoids and UV-B induced compounds enhanced with increasing the
      greening time. Activity of antioxidant enzymes catalase, peroxidase and
      superoxide dismutase increased during the seedlings greening and as a result of
      UV-B irradiation, but the pattern of isoforms remained similar to those found in
      the controls. UV-B preferentially induced Cu,Zn-superoxide dismutase. Increase of
      UVB induced synthesis of antioxidant enzymes is in line with their important role
      in the plant response to UV-B stress. Data presented show that the response of
      barley seedlings to UV-B irradiation is related to the development stage of
      photosynthetic apparatus.

PMID- 19584030
TI  - Effect of foliar feeding on nitrogen assimilation in alfalfa plants at
      insufficient molybdenum supply.
AB  - The influence of foliar feeding on the nitrogen assimilation in alfalfa plants
      under conditions of Mo shortage was studied. It was established that foliar
      fertilization with 0.3% solution of Agroleaf(r) resulted in increase of nitrogen
      fixation and nitrogen assimilation in the absence of Mo. Insufficient molybdenum
      supply leads to significant reduction of plant Mo content and nitrogen-fixing
      activity, while stress induced amino acids as alanine, GABA, threonine, proline
      and serine increased repeatedly. The negative effect of Mo deficiency on the
      enzyme activities related to the primary nitrogen assimilation (NR, GS, GOGAT)
      and plant growth diminished due to the foliar absorbed nutrients.

PMID- 19584031
TI  - Cytological changes in Turkish durum and bread wheat genotypes in response to
      salt stress.
AB  - Effects of salt stress on root growth, mitotic index, nuclear volume,
      vacuolization, nucleolar distortion and starch content were investigated in
      Turkish bread wheat ( Triticum aestivum L. cvs. Yildiz - salt sensitive, Dagdas -
      salt tolerant) and durum wheat ( Triticum durum L. cvs. C1252 - salt sensitive,
      Meramsalt tolerant) genotypes which were treated with 150 mM NaCI over a 6-day
      period. Salt treatment of wheat seedlings resulted in a decrease in root
      elongation and cell division in all genotypes at the 48 hours. According to
      controls, wheat root length decrease was 49% for Dagdas, 53.34% for Yildiz,
      25.34% for Meram, 53.68% for C1252 at the 48 h. Mitotic index showed a more
      significant decrease in sensitive genotypes (1.24% for Yildiz, 0.66% for C1252
      compairing to their controls 3.85% and 3.72%, respectively) of bread and durum
      wheat rather than tolerant ones (2.21% for Dagdas, 1.57% for Meram compairing to
      their controls 4.12% and 5.88%, respectively) at the 48 h of salt treatment.
      Calculated nuclear volume of wheat genotypes besides Dagdas showed a decline at
      the 48 h ranged from 1.57x10(5) to 2.13x10(5) MUm(3) . Vacuolization and nuclear
      distortion appeared on DAPI-stained preparations. There was a clear reduction in
      starch content in salt treated genotypes of durum wheat.

PMID- 19584032
TI  - Shoot development from hypocotyl protoplasts of sunflower (Helianthus annuus L.).
AB  - The plant regeneration from sunflower protoplast was achieved by protocols that
      considerably differ with respect to basal medium and concentration of growth
      regulators added. In most cases regeneration was restricted to a small proportion
      of genotypes. In this experiment, sunflower inbred line Ha-74A, with a high
      regeneration ability was used for protoplast isolation from etiolated hypocotyls.
      Isolated protoplasts were embedded in agarose droplets and cultured according to
      different regeneration protocols. The best results were obtained when protoplasts
      were cultured on L4 medium followed by transfer of regenerated microcalluses to
      solid regeneration media. Shoot regeneration was achieved by culture of calluses
      on SE regeneration medium after the treatment with 2.2 MUM thidiazuron.

PMID- 19584033
TI  - Discrimination between Bacteroides, Dichelobacter, Fusobacterium, Porphyromonas
      and Prevotella isolated from caprine footrot by PCR-RFLP - short communication.
AB  - Footrot is widely considered the most severe and most common foot pathology in
      small ruminants. This study tested the ability of a molecular typing system based
      on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      assay of the 16S rRNA gene to discriminate between the strict anaerobe genera
      most commonly isolated from footrot ( Bacteroides, Dichelobacter, Fusobacterium,
      Porphyromonas and Prevotella ) in goats in Extremadura (Spain), with a view to
      facilitating identification for diagnostic purposes and thus providing a useful
      tool for future epidemiological studies. Although the electrophoretic patterns
      obtained with the enzyme Tru 1I were more readily interpreted, and may thus be
      the best initial option, results may be confirmed by a second enzyme ( RsaI). The
      PCR-RFLP assay of the 16S rRNA gene may therefore prove a useful addition to
      conventional biochemical identification techniques, providing taxonomic
      information at genus level.

PMID- 19584034
TI  - Two-dimensional echocardiographic measurements of the left atrium in dogs with
      cardiac disease.
AB  - The aim of the present study was to verify the validity of two-dimensional
      echocardiographic (2DE) measurement technique in dogs with left atrial
      enlargement. Thirty-one dogs with clinically and echocardiographically proven
      cardiac diseases were randomly selected. The left atrial right-to-left diameter
      (La(r-l)) and the diameter of the left atrium just above the mitral annulus
      (La(ama)) as well as the ratio of left atrial to aortic diameter ( La/Ao ) were
      measured by 2DE. The La (r-l) / La(ama) ratio was independent of body weight
      (R(2) = 0.0006) and age (R(2) = 0.0012), respectively. A significant linear
      relationship was found between La(ama) and La/Ao (the ratio that expresses the
      severity of atrial enlargement): La(ama) = 1.2238 La/Ao + 1.1608 (R(2) = 021; P <
      0.01). There was also a positive linear relationship between La(r-l) and La/Ao :
      La(r-l) = 1.6876 La/Ao + 1.2648 (R(2) = 0.27; P < 0.005). In our dogs with
      cardiac disease, the La(r-l) / La(ama) ratio showed no significant relation to
      the La/Ao index (R(2) = 0.028). Thus, La(r-l) / La(ama) proved to be independent
      of the severity of atrial enlargement. Based on the strong relationship stated in
      the equation between La ama and La r-l [ La(r-l) / La(ama) = 1.31159 (95%
      confidence interval)], La(ama) can also be used for the assessment of left atrial
      size even in dogs with cardiac disease.

PMID- 19584035
TI  - M-mode and two-dimensional echocardiographic reference values for three Hungarian
      dog breeds: Hungarian Vizsla, Mudi and Hungarian Greyhound.
AB  - The aim of the study was to establish normal reference echocardiographic values
      for three Hungarian dog breeds, and to determine the potential dependence of
      intracardiac parameters on body weight, age and gender. M-mode and two
      dimensional echocardiography were performed on 95 clinically healthy dogs
      including 45 Hungarian Vizslas, 28 Mudis and 22 Hungarian Greyhounds. Linear
      intracardiac measurements included interventricular septal thickness (IVS), left
      ventricular internal diameter (LVID), left ventricular posterior wall thickness
      (LVPW) both in systole and diastole, as well as left atrial internal diameter
      (LAD), and aortic diameter (AOD) in early diastole. Fractional shortening (FS),
      end-diastolic and end-systolic left ventricular volumes (EDV and ESV), as well as
      LAD:AOD ratio were calculated from the linear parameters. Mean, range and
      standard deviation of measurements were calculated for each breed. Body weight
      positively correlated in all three breeds with all left ventricular dimensions,
      such as IVS d , IVS s , LVID d , LVIDD s , LVPW d and LVPW s parameters. LA
      values showed positive correlations to body weight in all three breeds. AOD and
      LA demonstrated a positive correlation with body weight in Hungarian Vizslas and
      Mudis, whilst the LAD:AOD ratio was related to body weight only in Mudis. Gender
      did not correlate with any of the measured echocardiographic parameters in any
      breeds. In Mudis, a positive correlation was found between the LAD: AOD ratio and
      age, as well as between the LAD: AOD ratio and E point to septal separation
      (EPSS).

PMID- 19584036
TI  - Effect of citric acid on electrocardiographic parameters of broiler chickens with
      pulmonary hypertension.
AB  - To clarify the effect of orally administered citric acid on the
      electrocardiographic parameters of pulmonary hypertensive broilers, chicks were
      reared at high altitude and treated with citric acid for 45 days. Increase of
      cardiac indices such as right ventricle/total ventricles (RV/TV), RV/body weight
      and TV/body weight ratio was not observed in the treated groups as compared to
      the control groups. Decrease of S amplitude in the treated groups (leads II, III,
      aVF) was only significant (P < 0.05) at 45 days of age (leads II, aVF; 1.5 g/l of
      citric acid). There were significant reductions of T amplitude at 28 (lead aVR)
      and 36 days (lead aVL) and significant reductions of R wave at 28 (lead aVL, all
      doses of citric acid) and 45 days of age (lead aVR, 1 and 1.5 g/l citric acid) in
      the treated groups. The QRS interval was significantly higher at 28 (leads III
      and aVF), 36 (leads II, III and aVF, 1 g/l citric acid) and 45 days of age (leads
      II and aVF) in the treated groups. The QT interval was significantly (P < 0.05)
      increased at 28 and 45 days of age (lead aVL) and the RR interval also showed an
      increase at 28 (leads aVR and aVL) and 45 (lead aVL) days of age as compared to
      the controls. Our data indicate that citric acid modulates the induction of
      pulmonary hypertension at high altitude and this effect is detectable in the
      electrocardiographic parameters.

PMID- 19584037
TI  - Novel monoclonal antibodies recognise guinea fowl thrombocytes.
AB  - This paper introduces two novel monoclonal antibodies, designated GTr1 and GTr2,
      which recognise guinea fowl thrombocyte surface antigen(s). The antibodies were
      tested in embryos and adult birds. GTr1 and GTr2 staining emerged at embryonic
      days 12 and 7, respectively. After embryonic day 12 there was no difference in
      staining pattern between the two monoclonal antibodies. The isotype of the
      antibodies is IgG1. The antibodies did not react with any other haematopoietic
      cells of guinea fowl, and there was no species cross-reaction with chicken,
      turkey and quail. The antibodies can be used in interspecies chimeric and
      parabiotic experiments to identify cells of guinea fowl origin.

PMID- 19584038
TI  - Pathological changes induced by rancid feed in rats and effects on growth and
      protein utilisation.
AB  - The objective of this trial was to study the effect of rancid feeds on the health
      status and growth of rats and to determine the pathological changes induced by
      dietary rancidity. Forty-two weaned male rats (body weight: 69.3 +/- 1.0 g) were
      divided into seven experimental groups (n = 6 each). Rats in the different groups
      were fed diets containing meat-and-bone meal at an inclusion rate of 19 to 22%,
      low or high in peroxides and high in organic acids, with or without antioxidant.
      The diets were isoproteic (10%) and isolipidic (6%). During the 26-day-long trial
      (5 days for adjustment and 21 days for the main period) the body weight gain and
      the feed consumption were recorded. At the end of the trial detailed gross and
      histopathological examinations were performed. Feeding high-peroxide feed
      mixtures for 21 days significantly (P < 0.05) decreased feed intake and
      liveweight gain, while high organic acid concentration had only slight negative
      effects. Antioxidant supplementation alleviated the harmful effects, especially
      in the high-peroxide group. The ingestion of rancid feed mixtures and the
      subsequent decreased feed intake caused a decrease of glycogen content in the
      hepatocytes, accompanied by a slight centrolobular fatty infiltration. Peroxides
      caused lymphocyte depletion in the spleen, decreased the size of Malpighian
      bodies and the number of lymphoblasts, and altered the spermatogenesis. The
      protective effect of the antioxidant mixture seemed to be negligible in this
      respect.

PMID- 19584039
TI  - Cutaneous mast cell tumour within a lipoma in a boxer.
AB  - This report describes a case of a canine cutaneous grade I mast cell tumour which
      developed within a lipoma in the right axillar region of an 8-year-old male
      Boxer. Immunohistologically, the neoplastic mast cells were positive for
      serotonin, CD45 vimentin and p53, and negative for lysozyme, CD3 and CD79a
      expression. The proliferation index of the mast cell tumour based on the Ki-67
      antigen was 6.1%. Between the benign neoplastic lipocytes and mastocytoma tumour
      cells intratumoural microvessels were detected by immunohistochemical staining
      using CD31 and claudin-5 as markers for vascular endothelium.

PMID- 19584040
TI  - Harderian gland adenocarcinoma in a Florida Red-bellied Turtle ( Pseudemys
      nelsoni ) - Case report.
AB  - The authors describe a case of unilateral adenocarcinoma emerging from the
      Harderian gland, filling the right orbital cavity of a Florida Red-bellied Turtle
      ( Pseudemys nelsoni ). The tumour did not produce any metastasis but presented an
      expansive growth and led to the dislocation and protrusion of the right eyeball.
      Histopathological analysis revealed the presence of numerous mitotic figures in
      the cellular population that made up the tumour. The tumour cells completely
      filled the alveoli of the gland and had a nest-like structure. The authors also
      emphasise the importance of the differential diagnosis of this rare pathological
      change in turtles. Epithelial hyperplasia of the Harderian gland's duct, observed
      in animals suffering from vitamin A deficiency, can also lead to an enlargement
      of the eyelid, but in these cases the change usually involves both eyelids
      symmetrically. This is the first description of a Harderian gland adenocarcinoma
      in a Florida Red-bellied Turtle.

PMID- 19584041
TI  - Crosstalk between coagulation and inflammation in mastitis and metritis in dairy
      cows.
AB  - Coagulation and inflammation are closely related as part of the mechanisms of
      host defence during a severe infection. The aim of this study was to investigate
      the relation between thrombin as a factor in both the coagulative and
      inflammatory processes and neutrophil secretory function on the basis of
      lactoferrin (LF), elastase and myeloperoxidase release in the course of mastitis
      and metritis in cows. Thrombin generation was measured on the basis of hydrolysis
      of SAR-PRO-ARG-pNA and lactoferrin concentration was estimated by an ELISA
      method. The greatest thrombin generation was observed in the metritis group (1.18
      +/- 0.62 IU). The level of LF was the highest in the group of cows with mastitis
      (0.74 +/- 0.55 mg/ml) in the first phase of the disease. In the second phase of
      the diseases the level of serum LF in cows with mastitis diminished to the value
      of 0.41 +/- 0.16 mg/ml, whereas in cows with metritis the level of LF increased
      to 0.51 +/- 0.17 mg/ml. This study reveals that the excessive production of
      thrombin not only causes hypercoagulatory disorders but also exaggerates
      neutrophil function by the release of some enzymes which may play a destructive
      role during disseminated intravascular coagulation (DIC). These enzymes also
      inhibit anticoagulative systems, thus potentially worsening the course of the
      disease.

PMID- 19584042
TI  - Alterations in some blood coagulation parameters in naturally occurring cases of
      canine babesiosis.
AB  - Changes in coagulation parameters were studied in dogs naturally infected with
      Babesia canis canis (n = 30), and haemostasis was evaluated and compared to
      values obtained from healthy dogs (n = 29). To date, there have not been any
      studies examining the dynamics of thrombin-antithrombin complex formation in
      cases of canine babesiosis. Coagulation parameters evaluated before (day 0) and
      on days 1, 2, and 3 after treatment with imidocarb (6 mg/kg inj. s.c.) included
      the determination of platelet counts, the formation of thrombin-antithrombin
      complexes (TAT), prothrombin time (PT), activated partial thromboplastin time
      (APTT) and antithrombin III (AT III) activity. TAT complexes were significantly
      elevated in animals with babesiosis on days 0 and 2 (mean 49.7 and 87.7 microg/L
      vs. control, 7.2 microg/L). AT III activity was significantly decreased at all
      time-points examined. There were no differences in PT. On days 2 and 3 the APTT
      was significantly shortened in the infected dogs when compared to control animals
      (means of 21.3 and 19.2 s vs. control, 30.0 s). Our analysis demonstrated that
      infected dogs had significant thrombocytopenia during the course of the study
      (mean day 0 - 29 x 10(9) /L, day 1 - 48 x 10(9) /L, day 2 - 47 x 10(9) /L and day
      3 - 87 x 10(9) /L, vs. control -259 x 10(9) /L). These data suggest that
      babesiosis in dogs compromise primary and secondary haemostasis and that
      induction of disseminated intravascular coagulation (DIC) occurs in canine
      babesiosis.

PMID- 19584043
TI  - Gross pathology, blood chemistry, lipid and peroxide contents in rainbow trout (
      Oncorhynchus mykiss Walbaum) affected by experimental Arcobacter cryaerophilus
      infection at low water temperature.
AB  - Arcobacter cryaerophilus was isolated from naturally infected rainbow trout (
      Oncorhynchus mykiss Walbaum), and its pathogenicity was tested by intramuscular
      injection using healthy 1-year-old rainbow trout under cold-water conditions (at
      5 degrees C). The lethal dosage of 50% end point (LD 50 ) for A. cryaerophilus
      was calculated as 7.79 x 10 5 viable cells. Experimental infection caused gross
      clinical abnormalities such as fallen scales, exophthalmia, oedema in injection
      region and at the base of fins, pale gills, kidney necrosis, hyperaemic areas in
      pale liver, haemorrhagic spots in heart, elongated spleen and swollen
      gallbladder. Activities of aspartate aminotransferase and alkaline phosphatase,
      and concentrations of glucose, total protein, albumin, cholesterol, triglyceride
      and calcium in the serum of the experimentally infected rainbow trout were
      significantly decreased compared with the healthy fish. Positive correlations
      were observed among blood parameters. Total lipid weights increased in the brain,
      muscle and liver tissues of infected fish and dropped in the gill and spleen
      tissues. Lipid peroxide contents in the brain, liver, kidney, spleen, muscle and
      gill tissues of infected rainbow trout were significantly higher than in healthy
      animals. The present work shows that A. cryaerophilus can be moderately virulent
      for rainbow trout at low water temperature, and changes in lipid and lipid
      peroxide contents of tissues and blood indices can highlight barely detectable
      effects of A. cryaerophilus infection in rainbow trout under laboratory
      conditions. However, the application of these indices in farm biomonitoring using
      rainbow trout will need more detailed studies and a careful consideration of the
      environmental parameters.

PMID- 19584044
TI  - Effects of energy restriction on thyroid hormone metabolism in chickens.
AB  - Energy restriction induces changes in thyroid hormone economy in the form of a
      complex adaptation mechanism, in order to conserve energy storage and protein
      reserves. In the present work, thyroid hormone serum concentrations, hepatic
      deiodinase enzyme activities and hepatic deiodinase mRNA expression were examined
      after feed restriction and fasting. We demonstrate that during energy
      restriction, T 3 concentration is lowered due to a decreased T 4 activation and
      increased T 3 inactivation. We show that hepatic type-I deiodinase (D1) is not
      affected by energy restriction, however, hepatic D2 is decreased on both
      transcriptional and enzyme activity levels. Furthermore, hepatic D3 is increased
      after feed restriction in the liver. We also show that the hypothalamic feedback
      is not involved in the changes in serum T 3 and T 4 concentrations. Our data
      indicate that D2 enzyme contributes to the special hormone-exporting role of the
      chicken liver and this enzyme can be modulated by feed restriction.

PMID- 19584045
TI  - Effects of melatonin treatment on follicular development and oocyte quality in
      Chios ewes - short communication.
AB  - Follicular development and oocyte quality were assessed by laparoscopic
      observation and in vitro fertilisation, respectively, in melatonin-treated (Group
      M) and control (Group C) anoestrous Chios ewes (n = 10 in each group). Fourteen
      days after melatonin insertion, all ewes had laparoscopic evaluation of the
      follicular population followed by oocyte pick-up (OPU); on day 22 intravaginal
      progestagen sponges were inserted for 14 days. Two days after sponge removal the
      follicular population was re-evaluated and a second follicular aspiration was
      performed. Collected oocytes from the second OPU underwent in vitro maturation,
      fertilisation and culture. The number of large follicles was higher in Group M
      than in the control ewes during the first OPU and tended to be so (P = 0.06) at
      the second. Morphologically, oocytes collected from controls were of better
      quality than those from Group M; however, more oocytes collected from
      melatonintreated animals fertilised and developed in vitro . These results
      indicate that melatonin is a potent regulator of follicular development and
      oocyte competence during the anoestrous period of the ewe.

PMID- 19584046
TI  - Papillomavirus-associated fibropapillomas of red deer ( Cervus elaphus ).
AB  - Oval, firm, cutaneous tumours with a rough, hairless, pigmented surface,
      exhibiting a moderately pronounced papillary structure were detected on the
      abdominal skin of two young red deer ( Cervus elaphus ). One animal was shot in
      Lower Austria in 2004, the other at a deer farm in Hungary in 2007. Histological
      examination of both samples classified the tumours as fibropapillomas, showing
      marked proliferation of fibroblasts and connective tissue, accompanied by
      hyperkeratosis, parakeratosis and acanthosis of the overlaying epidermis, and
      occasional foci of inflammation. The distribution of cytokeratin and vimentin was
      characterised in the lesion. The presence of papillomavirus (PV) antigen was
      demonstrated by immunohistochemistry in both cases. Papillomavirus-specific DNA
      was successfully amplified by PCR from one sample. The obtained partial
      nucleotide sequence of the L2 ORF exhibited the highest critical identity values
      with the homologous regions of Delta-papillomaviruses, especially the Roe deer
      papillomavirus (93%). Phylogenetic analysis of the partial L2 ORF sequence
      alignment of 10 papillomaviruses by both neighbour-joining and maximum parsimony
      method confirmed that the Red deer PV is very closely related to the Western roe
      deer papillomavirus (CcPV1).

PMID- 19584048
TI  - Hypochlorous acid converts the gamma-glutamyl group of glutathione disulfide to 5
      hydroxybutyrolactam, a potential marker for neutrophil activation.
AB  - In healthy cells, glutathione disulfide (GSSG) is rapidly reduced back to
      glutathione (GSH) by glutathione reductase to maintain redox status. The ratio of
      GSH/GSSG has been used as an indicator of oxidative stress. However, hypochlorous
      acid (HOCl) generated by the myeloperoxidase-H(2)O(2)-Cl(-) system of neutrophils
      converts GSH to irreversible oxidation products. Although several such products
      have been identified, yields of these compounds are very low in biological
      systems, and they cannot account quantitatively for thiol loss. In the current
      studies, we use liquid chromatography-mass spectrometry (LC-MS) to demonstrate
      that HOCl and chloramines oxidize GSSG to two irreversible products in high
      yield. The products, termed M-45 and M-90, are, respectively, 45 or 90 atomic
      mass units lighter than GSSG. The reaction pathway involves chloramine and
      aldehyde intermediates, and converts the gamma-glutamyl residues of GSSG to 5
      hydroxybutyrolactam. Importantly, M-45 and M-90 were resistant to reduction by
      glutathione reductase. Moreover, the monohydroxylbutyrolactam M-45 accounted for
      >90% of the endogenous GSH oxidation products generated by activated neutrophils.
      Because the reaction pathway involves chlorinating intermediates,
      hydroxylbutyrolactams are likely to be specific products of HOCl, which is
      generated only by myeloperoxidase. Therefore, our observations implicate M-45 as
      a potential biomarker for myeloperoxidase activity in vivo.

PMID- 19584049
TI  - The double-stranded RNA binding domain of the vaccinia virus E3L protein inhibits
      both RNA- and DNA-induced activation of interferon beta.
AB  - Vaccinia virus, a large DNA virus that replicates in the cytoplasm, expresses its
      E3L protein to inhibit the cellular innate immune response and apoptosis. E3L is
      a bifunctional protein that contains an N-terminal DNA binding domain (BD) and a
      C-terminal double-stranded RNA (dsRNA)-BD (residues 100-190), both of which
      contribute to viral pathogenesis by blocking the activation of cellular genes
      that respond to the viral infection. We report that expression of the dsRNA-BD
      alone inhibits not only the dsRNA-induced activation of interferon beta (IFNbeta)
      but also that of 5'-triphosphate single-stranded RNA and DNA-induced IFNbeta
      activation even though E3L(100-190) does not bind the latter two pathogen
      associated molecular patterns. This inhibition occurs in both human HeLa and A549
      cells, where RIG-I appears to be required for dsDNA-induced IFNbeta activation.
      Unexpectedly, the two residues most important for dsRNA binding are also critical
      for this domain's ability to inhibit all three nucleic acid-induced cellular
      responses.

PMID- 19584050
TI  - The human malaria parasite Plasmodium falciparum is not dependent on host
      coenzyme A biosynthesis.
AB  - Pantothenate, a precursor of the fundamental enzyme cofactor coenzyme A (CoA), is
      essential for growth of the intraerythrocytic stage of human and avian malaria
      parasites. Avian malaria parasites have been reported to be incapable of de novo
      CoA synthesis and instead salvage CoA from the host erythrocyte; hence,
      pantothenate is required for CoA biosynthesis within the host cell and not the
      parasite itself. Whether the same is true of the intraerythrocytic stage of the
      human malaria parasite, Plasmodium falciparum, remained to be established. In
      this study we investigated the metabolic fate of [(14)C]pantothenate within
      uninfected and P. falciparum-infected human erythrocytes. We provide evidence
      consistent with normal human erythrocytes, unlike rat erythrocytes (which have
      been reported to possess an incomplete CoA biosynthesis pathway), being capable
      of CoA biosynthesis from pantothenate. We also show that CoA biosynthesis is
      substantially higher in P. falciparum-infected erythrocytes and that P.
      falciparum, unlike its avian counterpart, generates most of the CoA synthesized
      in the infected erythrocyte, presumably necessitated by insufficient CoA
      biosynthesis in the host erythrocyte. Our data raise the possibility that malaria
      parasites rationalize their biosynthetic activity depending on the capacity of
      their host cell to synthesize the metabolites they require.

PMID- 19584051
TI  - Mitochondrial glutamate carrier GC1 as a newly identified player in the control
      of glucose-stimulated insulin secretion.
AB  - The SLC25 carrier family mediates solute transport across the inner mitochondrial
      membrane, a process that is still poorly characterized regarding both the
      mechanisms and proteins implicated. This study investigated mitochondrial
      glutamate carrier GC1 in insulin-secreting beta-cells. GC1 was cloned from
      insulin-secreting cells, and sequence analysis revealed hydropathy profile of a
      six-transmembrane protein, characteristic of mitochondrial solute carriers. GC1
      was found to be expressed at the mRNA and protein levels in INS-1E beta-cells and
      pancreatic rat islets. Immunohistochemistry showed that GC1 was present in
      mitochondria, and ultrastructural analysis by electron microscopy revealed inner
      mitochondrial membrane localization of the transporter. Silencing of GC1 in INS
      1E beta-cells, mediated by adenoviral delivery of short hairpin RNA, reduced
      mitochondrial glutamate transport by 48% (p < 0.001). Insulin secretion at basal
      2.5 mM glucose and stimulated either by intermediate 7.5 mM glucose or non
      nutrient 30 mM KCl was not modified by GC1 silencing. Conversely, insulin
      secretion stimulated with optimal 15 mM glucose was reduced by 23% (p < 0.005) in
      GC1 knocked down cells compared with controls. Adjunct of cell-permeant glutamate
      (5 mM dimethyl glutamate) fully restored the secretory response at 15 mM glucose
      (p < 0.005). Kinetics of insulin secretion were investigated in perifused
      isolated rat islets. GC1 silencing in islets inhibited the secretory response
      induced by 16.7 mM glucose, both during first (-25%, p < 0.05) and second (-33%,
      p < 0.05) phases. This study demonstrates that insulin-secreting cells depend on
      GC1 for maximal glucose response, thereby assigning a physiological function to
      this newly identified mitochondrial glutamate carrier.

PMID- 19584053
TI  - D-xylose degradation pathway in the halophilic archaeon Haloferax volcanii.
AB  - The pathway of D-xylose degradation in archaea is unknown. In a previous study we
      identified in Haloarcula marismortui the first enzyme of xylose degradation, an
      inducible xylose dehydrogenase (Johnsen, U., and Schonheit, P. (2004) J.
      Bacteriol. 186, 6198-6207). Here we report a comprehensive study of the complete
      D-xylose degradation pathway in the halophilic archaeon Haloferax volcanii. The
      analyses include the following: (i) identification of the degradation pathway in
      vivo following (13)C-labeling patterns of proteinogenic amino acids after growth
      on [(13)C]xylose; (ii) identification of xylose-induced genes by DNA microarray
      experiments; (iii) characterization of enzymes; and (iv) construction of in-frame
      deletion mutants and their functional analyses in growth experiments. Together,
      the data indicate that D-xylose is oxidized exclusively to the tricarboxylic acid
      cycle intermediate alpha-ketoglutarate, involving D-xylose dehydrogenase
      (HVO_B0028), a novel xylonate dehydratase (HVO_B0038A), 2-keto-3-deoxyxylonate
      dehydratase (HVO_B0027), and alpha-ketoglutarate semialdehyde dehydrogenase
      (HVO_B0039). The functional involvement of these enzymes in xylose degradation
      was proven by growth studies of the corresponding in-frame deletion mutants,
      which all lost the ability to grow on d-xylose, but growth on glucose was not
      significantly affected. This is the first report of an archaeal D-xylose
      degradation pathway that differs from the classical D-xylose pathway in most
      bacteria involving the formation of xylulose 5-phosphate as an intermediate.
      However, the pathway shows similarities to proposed oxidative pentose degradation
      pathways to alpha-ketoglutarate in few bacteria, e.g. Azospirillum brasilense and
      Caulobacter crescentus, and in the archaeon Sulfolobus solfataricus.

PMID- 19584052
TI  - Anionic pulmonary surfactant phospholipids inhibit inflammatory responses from
      alveolar macrophages and U937 cells by binding the lipopolysaccharide-interacting
      proteins CD14 and MD-2.
AB  - Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause
      of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is
      secreted as a complex mixture of lipids and proteins onto the alveolar surface of
      the lung. Surfactant phospholipids are essential in reducing surface tension at
      the air-liquid interface and preventing alveolar collapse at the end of the
      respiratory cycle. In the present study, we determined that palmitoyl-oleoyl
      phosphatidylglycerol and phosphatidylinositol, which are minor components of
      pulmonary surfactant, and synthetic dimyristoylphosphatidylglycerol regulated the
      inflammatory response of alveolar macrophages. The anionic lipids significantly
      inhibited LPS-induced nitric oxide and tumor necrosis factor-alpha production
      from rat and human alveolar macrophages and a U937 cell line by reducing the LPS
      elicited phosphorylation of multiple intracellular protein kinases. The anionic
      lipids were also effective at attenuating inflammation when administered
      intratracheally to mice challenged with LPS. Binding studies revealed high
      affinity interactions between the palmitoyl-oleoyl-phosphatidylglycerol and the
      Toll-like receptor 4-interacting proteins CD14 and MD-2. Our data clearly
      identify important anti-inflammatory properties of the minor surfactant
      phospholipids at the environmental interface of the lung.

PMID- 19584054
TI  - The transcription factor Atf1 binds and activates the APC/C ubiquitin ligase in
      fission yeast.
AB  - Fission yeast Atf1 is a member of the ATF/CREB basic leucine zipper (bZIP) family
      of transcription factors with strong homology to mammalian ATF2. Atf1 regulates
      transcription in response to stress stimuli and also plays a role in controlling
      heterochromatin formation and recombination. However, its DNA binding independent
      role is poorly studied. Here, we report that Atf1 has a distinct role in
      regulating the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. We
      have identified atf1(+) as a dose-dependent suppressor of apc5-1, a mutation
      causing mitotic arrest. Remarkably, the suppression is not dependent upon the
      bZIP domain and is therefore independent of the ability of Atf1 to bind DNA.
      Interestingly, Atf1 physically binds the APC/C in vivo. Furthermore, we show that
      addition of purified Atf1 proteins into a cell-free system stimulates
      ubiquitylation of cyclin B and securin by the APC/C. These results reveal a novel
      role for Atf1 in cell cycle control through protein-protein interaction.

PMID- 19584055
TI  - Glycosylated hydroxytryptophan in a mussel adhesive protein from Perna viridis.
AB  - The 3,4-dihydroxyphenyl-l-alanine (Dopa)-containing proteins of mussel byssus
      play a critical role in wet adhesion and have inspired versatile new synthetic
      strategies for adhesives and coatings. Apparently, however, not all mussel
      adhesive proteins are beholden to Dopa chemistry. The cDNA-deduced sequence of
      Pvfp-1, a highly aromatic and redox active byssal coating protein in the green
      mussel Perna viridis, suggests that Dopa may be replaced by a post-translational
      modification of tryptophan. The N-terminal tryptophan-rich domain of Pvfp-1
      contains 42 decapeptide repeats with the consensus sequences ATPKPW(1)TAW(2)K and
      APPPAW(1)TAW(2)K. A small collagen domain (18 Gly-X-Y repeats) is also present.
      Tandem mass spectrometry of isolated tryptic decapeptides has detected both C(2)
      hexosylated tryptophan (W(1)) and C(2)-hexosylated hydroxytryptophan (W(2)), the
      latter of which is redox active. The UV absorbance spectrum of W(2) is consistent
      with 7-hydroxytryptophan, which represents an intriguing new theme for
      bioinspired opportunistic wet adhesion.

PMID- 19584056
TI  - miR-331-3p regulates ERBB-2 expression and androgen receptor signaling in
      prostate cancer.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and
      are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is
      frequently overexpressed in prostate cancer and is associated with disease
      progression and poor survival. We have identified two specific miR-331-3p target
      sites within the ERBB-2 mRNA 3'-untranslated region and show that miR-331-3p
      expression is decreased in prostate cancer tissue relative to normal adjacent
      prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331
      3p reduced ERBB-2 mRNA and protein expression and blocked downstream
      phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection
      blocked the androgen receptor signaling pathway in prostate cancer cells,
      reducing activity of an androgen-stimulated prostate-specific antigen promoter
      and blocking prostate-specific antigen expression. Our findings provide insight
      into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p
      has the capacity to regulate signaling pathways critical to the development and
      progression of prostate cancer cells.

PMID- 19584057
TI  - Pin1 catalyzes conformational changes of Thr-187 in p27Kip1 and mediates its
      stability through a polyubiquitination process.
AB  - The cis-trans peptidylprolyl isomerase Pin1 plays a critical role in regulating a
      subset of phosphoproteins by catalyzing conformational changes on the
      phosphorylated Ser/Thr-Pro motifs. The phosphorylation-directed ubiquitination is
      one of the major mechanisms to regulate the abundance of p27(Kip1). In this
      study, we demonstrate that Pin1 catalyzes the cis-trans conformational changes of
      p27(Kip1) and further mediates its stability through the polyubiquitination
      mechanism. Our results show that the phosphorylated Thr-187-Pro motif in
      p27(Kip1) is a key Pin1-binding site. In addition, NMR analyses show that this
      phosphorylated Thr-187-Pro site undergoes conformational change catalyzed by
      Pin1. Moreover, in Pin1 knock-out mouse embryonic fibroblasts, p27(Kip1) has a
      shorter lifetime and displays a higher degree of polyubiquitination than in Pin1
      wild-type mouse embryonic fibroblasts, suggesting that Pin1 plays a critical role
      in regulating p27(Kip1) degradation. Additionally, Pin1 dramatically reduces the
      interaction between p27(Kip1) and Cks1, possibly via isomerizing the cis-trans
      conformation of p27(Kip1). Our study thus reveals a novel regulatory mechanism
      for p27(Kip1) stability and sheds new light on the biological function of Pin1 as
      a general regulator of protein stability.

PMID- 19584058
TI  - Coupling of Ca(2+) microdomains to spatially and temporally distinct cellular
      responses by the tyrosine kinase Syk.
AB  - Communication between the cell surface and the nucleus is essential for regulated
      gene expression. In neurons, Ca(2+)-dependent gene transcription is sensitive to
      local Ca(2+) entry. In immune cells, excitation-transcription coupling is thought
      to involve global Ca(2+) signals. Here, we show that in mast cells, Ca(2+)
      microdomains from store-operated Ca(2+) release-activated Ca(2+) channels
      activate expression of the transcription factor c-fos. Local Ca(2+) entry is
      sensed by the tyrosine kinase Syk, which signals to the nucleus through the
      transcription factor STAT5. Ca(2+) microdomains also promote secretion of
      proinflammatory messengers, which, like gene expression, requires Syk. Syk
      therefore couples Ca(2+) microdomains to the activation of two spatially and
      temporally distinct cellular responses, revealing the versatility of local Ca(2+)
      signals in driving cell activation.

PMID- 19584059
TI  - Nuclear factor-kappaB regulates estrogen receptor-alpha transcription in the
      human heart.
AB  - Estrogen receptor (ER)-mediated effects have been associated with the modulation
      of myocardial hypertrophy in animal models and in humans, but the regulation of
      ER expression in the human heart has not yet been analyzed. In various cell lines
      and tissues, multiple human estrogen receptor alpha (hERalpha) mRNA isoforms are
      transcribed from distinct promoters and differ in their 5'-untranslated regions.
      Using PCR-based strategies, we show that in the human heart the ERalpha mRNA is
      transcribed from multiple promoters, namely, A, B, C, and F, of which the F
      promoter is most frequently used variant. Transient transfection reporter assays
      in a human cardiac myocyte cell line (AC16) with F-promoter deletion constructs
      demonstrated a negative regulatory region within this promoter. Site-directed
      mutagenesis and electrophoretic mobility shift assays indicated that NF-kappaB
      binds to this region. An inhibition of NF-kappaB activity by parthenolide
      significantly increased the transcriptional activity of the F-promoter.
      Increasing NF-kappaB expression by tumor necrosis factor-alpha reduced the
      expression of ERalpha, indicating that the NF-kappaB pathway inhibits expression
      of ERalpha in human cardiomyocytes. Finally, 17beta-estradiol induced the
      transcriptional activity of hERalpha promoters A, B, C, and F. In conclusion,
      inflammatory stimuli suppress hERalpha expression via activation and subsequent
      binding of NF-kappaB to the ERalpha F-promoter, and 17beta-estradiol/hERalpha may
      antagonize the inhibitory effect of NF-kappaB. This suggests interplay between
      estrogen/estrogen receptors and the pro-hypertrophic and inflammatory responses
      to NF-kappaB.

PMID- 19584060
TI  - Solution structure of human Pex5.Pex14.PTS1 protein complexes obtained by small
      angle X-ray scattering.
AB  - The Pex5p receptor recognizes newly synthesized peroxisomal matrix proteins which
      have a C-terminal peroxisomal targeting signal to the peroxisome. After docking
      to protein complexes on the membrane, these proteins are translocated across the
      membrane. The docking mechanism remains unclear, as no structural data on the
      multicomponent docking complex are available. As the interaction of the cargo
      loaded Pex5p receptor and the peroxisomal membrane protein Pex14p is the
      essential primary docking step, we have investigated the solution structure of
      these complexes by small angle x-ray scattering and static light scattering.
      Titration studies yielded a 1:6 stoichiometry for the Pex5p.Pex14p complex, and
      low resolution structural models were reconstructed from the x-ray scattering
      data. The free full-length human Pex5p is monomeric in solution, with an
      elongated, partially unfolded N-terminal domain. The model of the complex reveals
      that the N terminus of Pex5p remains extended in the presence of cargo and
      Pex14p, the latter proteins being significantly intermingled with the Pex5p
      moiety. These results suggest that the extended structure of Pex5p may play a
      role in interactions with other substrates such as lipids and membrane proteins
      during the formation of functional multiprotein complexes.

PMID- 19584061
TI  - Referrals into a dedicated British penile cancer centre and sources of possible
      delay.
AB  - OBJECTIVE: To assess sources of delay in referral to a specialist Urology clinic
      for penile cancer. METHODS: Patients with penile cancer seen during the period
      December 2002 to December 2007 were identified from the unit's database.
      Information regarding presentation, diagnosis and pattern of referral was
      retrieved from records. Delay was defined as the time between the patient first
      noticing a penile lesion and date of first seeking medical advice, or additional
      time before being seen by a Urologist resulting from referral to another
      specialty. RESULTS: Of 100 patients, with a median age of 54 years (range 2-81
      years), 19% were initially referred to other specialties (Genitourinary Medicine
      13%, Dermatology-4%, Plastics 2%). Initial referrals to Genito-urinary Medicine
      and Dermatology resulted in mean delays of 6 and 3.5 months respectively, whereas
      the mean duration for patients to present to any medical practitioner from onset
      of symptoms was 5.8 months. Overall, 47% presented with locally advanced disease.
      CONCLUSION: Approximately one-fifth of patients with penile cancer are first
      referred to specialties other than Urology. This sometimes delays diagnosis,
      potentially affecting overall prognosis. The major source of delay, however,
      results from patient reluctance to seek medical advice. Thus, the greatest impact
      in this condition is likely to be achieved by increased public awareness and
      education.

PMID- 19584062
TI  - Absolute myocardial blood flow determination using real-time myocardial contrast
      echocardiography during adenosine stress: comparison with single-photon emission
      computed tomography.
AB  - OBJECTIVE: To assess the feasibility and diagnostic accuracy of real-time
      myocardial contrast echocardiography (MCE)-derived absolute myocardial blood flow
      for detection of myocardial perfusion abnormalities compared with simultaneous
      technetium 99 m sestamibi single-photon emission computed tomography (SPECT).
      DESIGN: Prospective study. SETTING: Tertiary-care medical institution. PATIENTS:
      79 patients with known or suspected coronary artery disease. INTERVENTIONS:
      Simultaneous SPECT and real-time MCE during adenosine stress. MAIN OUTCOME
      MEASURES: Absolute myocardial blood flow (MBF, ml/min/g), microbubble velocity
      (beta, min(-1)), and reserve values. Endpoints included sensitivity, specificity,
      positive likelihood ratio (LR+) or negative likelihood ratio (LR-) and area under
      the curve (AUC) of the receiver operating characteristic curve. RESULTS: Reserve
      measurements were feasible in 975 of 1343 segments (73%); of these, 130 segments
      (13%) were abnormal by SPECT. MCE perfusion parameters clearly distinguished
      abnormal from normal segments for beta reserve (1.13 (0.99) vs 2.22 (1.36),
      p<0.001) and MBF reserve (1.80 (2.29) vs 3.69 (2.79), p<0.001). The beta reserve
      cut-off of 1.60 provided the following: AUC, 0.787; sensitivity, 82%;
      specificity, 66%; LR+, 2.40; and LR-, 0.28. The MBF reserve cut-off of 1.90
      provided the following: AUC, 0.779; sensitivity, 73%; specificity, 72%; LR+,
      2.69; and LR-, 0.37. MBF reserve had an AUC of 0.773 for the left anterior
      descending coronary artery, 0.885 for the left circumflex coronary artery and
      0.739 for the right coronary artery. CONCLUSIONS: Real-time MCE-derived absolute
      MBF, beta, and reserve values are feasible and accurate for detecting myocardial
      perfusion abnormalities as defined by SPECT.

PMID- 19584063
TI  - Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome
      17p13.3 result in facial dysmorphisms, growth restriction, and cognitive
      impairment.
AB  - BACKGROUND: Deletions in the 17p13.3 region are associated with abnormal neuronal
      migration. Point mutations or deletion copy number variants of the PAFAH1B1 gene
      in this genomic region cause lissencephaly, whereas extended deletions involving
      both PAFAH1B1 and YWHAE result in Miller-Dieker syndrome characterised by facial
      dysmorphisms and a more severe grade of lissencephaly. The phenotypic
      consequences of YWHAE deletion without deletion of PAFAH1B1 have not been studied
      systematically. METHODS: We performed a detailed clinical and molecular
      characterization of five patients with deletions involving YWHAE but not
      PAFAH1B1, two with deletion including PAFAH1B1 but not YWHAE, and one with
      deletion of YWHAE and mosaic for deletion of PAFAH1B1. RESULTS: Three deletions
      were terminal whereas five were interstitial. Patients with deletions including
      YWHAE but not PAFAH1B1 presented with significant growth restriction, cognitive
      impairment, shared craniofacial features, and variable structural abnormalities
      of the brain. Growth restriction was not observed in one patient with deletion of
      YWHAE and TUSC5, implying that other genes in the region may have a role in
      regulation of growth with CRK being the most likely candidate. Using array based
      comparative genomic hybridisation and long range polymerase chain reaction, we
      have delineated the breakpoints of these nonrecurrent deletions and show that the
      interstitial genomic rearrangements are likely generated by diverse mechanisms,
      including the recently described Fork Stalling and Template Switching
      (FoSTeS)/Microhomology Mediated Break Induced Replication (MMBIR). CONCLUSIONS:
      Microdeletions of chromosome 17p13.3 involving YWHAE present with growth
      restriction, craniofacial dysmorphisms, structural abnormalities of brain and
      cognitive impairment. The interstitial deletions are mediated by diverse
      molecular mechanisms.

PMID- 19584064
TI  - ABCB4 gene mutations and single-nucleotide polymorphisms in women with
      intrahepatic cholestasis of pregnancy.
AB  - AIM: To evaluate the nature and frequency of ATP-binding cassette subfamily B
      member 4 (ABCB4) gene variants in a series of French patients with intrahepatic
      cholestasis of pregnancy (ICP). METHODS: In this prospective study, the entire
      ABCB4 gene coding sequence was analysed by DNA sequencing in 50 unrelated women
      with ICP defined by pruritus and raised serum alanine aminotransferase activity
      or bile acid concentration, with recovery after delivery. Genomic variants
      detected in patients with ICP were sought in 107 control pregnant women. Patients
      with ICP and controls were of Caucasian origin. RESULTS: Eight genomic variants
      were observed. One nonsense mutation (p.Arg144Stop) and two missense mutations
      (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A
      third missense mutation (p.Arg590Gln) was detected in three heterozygous patients
      and in two homozygous patients also homozygous for a particular haplotype of
      three single-nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The
      chromosomal frequency of the p.Arg590Gln variant was significantly different
      between the ICP and control group (7.0% vs 0.5%; p = 0.0017; OR 16.03, 95% CI
      1.94 to 132.16). An association was also found between allele T of the c.504T>C
      silent nucleotide polymorphism and ICP (68.0% vs 53.7%; p = 0.017; OR 1.83, 95%
      CI 1.08 to 3.11). The chromosomal frequency of the p.Arg652Gly variant did not
      differ between the ICP and control group (p = 0.40). CONCLUSIONS: This study
      shows that 16% of Caucasian patients with ICP bear ABCB4 gene mutations, and
      confirms the significant involvement of this gene in the pathogenesis of this
      complex disorder.

PMID- 19584065
TI  - Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split
      hand foot malformation (SHFM) are caused by chromosome 10q genomic
      rearrangements.
AB  - BACKGROUND: The 10q24 chromosomal region has previously been implicated in split
      hand foot malformation (SHFM). SHFM3 was mapped to a large interval on chromosome
      10q. The corresponding dactylaplasia mouse model was linked to the syntenic locus
      on chromosome 19. It was shown that the two existing Dac alleles result from MusD
      insertions upstream of or within Dactylin (Fbxw4). However, all efforts to find
      the underlying cause for the human SHFM3 have failed on the analysis of all the
      genes within the linkage region. Intriguingly a submicroscopic duplication within
      the critical locus on chromosome 10q24 was associated with the phenotype. METHODS
      AND RESULTS: As a part of screening for genomic rearrangements in cases with
      unexplained syndromic limb defects, a cohort of patients was analysed by array
      comparative genomic hybridisation (CGH). A 10q24 microduplication was detected in
      two individuals with distal limb deficiencies associated with micrognathia,
      hearing problems and renal hypoplasia. In addition, in a family with two affected
      siblings, a somatic/gonadal mosaicism for the microduplication was detected in
      the apparently healthy mother. Using a high resolution oligoarray further
      delineation of the duplication size was performed. CONCLUSIONS: The detected
      10q24 genomic imbalance in our syndromic patients has a similar size to the
      duplication in the previously reported individuals with an isolated form of SHFM,
      thus extending the clinical spectrum of SHFM3. These findings clearly demonstrate
      the importance of array CGH in the detection of the aetiology of complex,
      clinically heterogeneous entities.

PMID- 19584066
TI  - Evidence for human microRNA-offset RNAs in small RNA sequencing data.
AB  - MicroRNA-offset-RNAs (moRNAs) were recently detected as highly abundant class of
      small RNAs in a basal chordate. Using short read sequencing data, we show here
      that moRNAs are also produced from human microRNA precursors, albeit at quite low
      expression levels. The expression levels of moRNAs are unrelated to those of the
      associated microRNAs. Surprisingly, microRNA precursors that also show moRNAs are
      typically evolutionarily old, comprising more than half of the microRNA families
      that were present in early Bilateria, while evidence for moRNAs was found only
      for a relative small fraction of microRNA families of recent origin.

PMID- 19584067
TI  - Identification of distant family relationships.
AB  - MOTIVATION: Family relationships can be estimated from DNA marker data.
      Applications arise in a large number of areas including evolution and
      conservation research, genealogical research in human, plant and animal
      populations, forensic problems and genetic mapping via linkage and association
      analyses. Traditionally, likelihood-based approaches to relationship estimation
      have used unlinked genetic markers. Due to the fact that some relationships
      cannot be distinguished from data at unlinked markers, and given the limited
      number of such markers available, there are considerable constraints on the type
      of identification problem that can be satisfactorily addressed with such
      approaches. The aim of this article is to explore the potential of linked
      autosomal single nucleotide polymorphism markers in this context. Throughout, we
      will view the problem of relationship estimation as one of pedigree
      identification rather than identity-by-descent, and thus focus on applications
      where determination of the exact relationship is important. RESULTS: We show that
      the increase in information obtained by exploiting large sets of linked markers
      substantially increases the number of problems that can be solved. Results are
      presented based on simulations as well as on real data. AVAILABILITY: The R
      library FEST is freely available from http://folk.uio.no/thoree/FEST.

PMID- 19584068
TI  - Cardioprotective effects of normothermic reperfusion with oxygenated potassium
      cardioplegia: a possible mechanism.
AB  - Na(+)/K(+) pump activation induced by normothermic reperfusion with high
      potassium cardioplegia may exert a protective effect on reperfusion-induced
      myocardial damage. We investigated (1) temperature dependency and extracellular
      potassium dependency of the Na(+)/K(+) pump current (Ip), (2) effects of high
      potassium or ouabain during reperfusion on the post-ischemic left ventricular
      (LV) function. Ip-voltage relation was constructed at 5.0 and 20 mM of KCl (37
      degrees C) using a whole-cell clamp technique in guinea pig myocytes. Ip at -40
      mV was measured at 37, 27 and 18 degrees C (KCl: 5.0 mM). Isolated rat hearts
      were Langendorff-perfused and subjected to 20 min of global ischemia (37 degrees
      C) followed by 35 min of reperfusion (37 degrees C). The post-ischemic recovery
      of LV developed pressure (%LVDP) was assessed in the four reperfusate groups (4.8
      mM KCl, 10 mM KCl, 20 mM KCl, or 4.8 mM KCl plus 50 microM ouabain during the
      first 10 min of reperfusion). The 4.8 mM KCl and 10.0 mM KCl groups were compared
      under metabolic inhibition (glucose-free, NaCN, or hypoxia) during reperfusion.
      The Ip-voltage relation shifted upward when extracellular KCl was increased from
      5.0 to 20 mM. Ip was significantly greater at 37 degrees C than at 18 degrees C
      (114.3+/-17.2 vs. 22.7+/-1.2 pA, respectively). %LVDP was significantly greater
      at the 10.0 mM KCl group than at the 4.8 mM KCl group (54.9+/-5.5% vs. 34.2+/
      5.9%, respectively). Metabolic inhibition abolished the difference between the
      two groups. Ouabain significantly decreased %LVDP (15.9+/-1.6%). Potassium
      induced cardiac arrest during normothermic reperfusion may exert a
      cardioprotective effect by inducing Na(+)/K(+) pump activation, which may be
      supported by aerobic metabolism during reoxygenation rather than by energy saving
      during cardiac arrest.

PMID- 19584069
TI  - Apico-aortic conduit for aortic stenosis with a porcelain aorta; technical
      modification for apical outflow.
AB  - A successful apico-aortic bypass for a patient with a porcelain aorta suffering
      from aortic stenosis is reported. A sewing cuff with an outflow graft to the apex
      and a hand-made composite graft were used instead of a rigid apical connector.

PMID- 19584070
TI  - Age- and gender-specific values of estimated glomerular filtration rate among
      6232 patients undergoing cardiac surgery.
AB  - Impaired preoperative renal function as estimated by glomerular filtration rate
      (GFR) is an independent risk factor for mortality after cardiac surgery. Little
      is known about the actual prevalence of renal dysfunction among patients
      undergoing cardiac surgery in Germany. We performed a retrospective analysis of
      6232 patients from 20 to 80 years. GFR was estimated with the modification of
      diet in renal disease (MDRD) formula. There was an age-dependent decrease in
      estimated glomerular filtration rates (eGFR) among both men and women. There is a
      stepwise age-dependent increase of chronic kidney disease (CKD) stages 3-5 (<60
      ml/min/1.73 m(2)). The lower the eGFR the higher the risk for mortality [odds
      ratio 2.93 95%-confidence interval (CI) 1.92-4.53] for eGFR<30 ml/min/1.73 m(2);
      odds ratio 1.93 (95%-CI 1.56-2.39) for eGFR 30-60 ml/min/1.73 m(2) compared to
      patients with an eGFR>60 ml/min/1.73 m(2). The actual mortality rates varied
      between 6.3% (307/4869) for patients with an eGFR>60 ml/min/1.73 m(2), 11.3%
      (137/1051) for patients with an eGFR of 30-60 ml/min/1.73 m(2) and 16.6% (27/163)
      for patients with an eGFR<30 ml/min/1.73 m(2). Estimated GFR declines are age-
      and gender-dependent. Preoperative renal dysfunction is an important predictor of
      in-hospital mortality after cardiac surgery.

PMID- 19584071
TI  - Brain natriuretic peptide a predictive marker in cardiac surgery.
AB  - BACKGROUND: BNP which stands for B-type natriuretic peptide is a cardiac
      neurohormone and is secreted in response to myocardial stress and causes
      natriuresis and vasodilatation. Studies have reported close correlation between a
      high concentration of BNP in blood and worse short-term and long-term prognosis
      following myocardial infarction and heart failure. In this study, we have tested
      its usefulness and predictive value in the outcome post cardiac surgery. METHODS:
      Between March 2006 and June 2007, 141 patients, undergoing cardiac surgery, were
      enrolled in this study. Their BNP concentration was measured prior to the
      operation and their comorbidities were examined against their BNP levels.
      Postoperatively their outcome was closely monitored. Main clinical endpoints were
      atrial fibrillation (AF), inotrope use, renal impairment, early deaths and
      hospital stay. RESULTS: Some preoperative comorbidities, such as renal
      impairment, peripheral vascular disease (PVD) and low ejection fraction (EF) were
      associated with higher BNP level. Statistically, EuroSCORE and Parsonnet score
      showed significant correlation with preoperative BNP concentration (P<0.0001).
      Postoperatively, high-BNP concentration predicted inotropic use, higher than
      baseline creatinine level, longer ventilation time, longer hospital stay and
      early mortality (P<0.05) but our study did not reveal any predictive value for
      BNP in identifying those developing AF or infection postoperatively. CONCLUSIONS:
      BNP is a valuable biochemical marker, which is easy to measure and can be
      beneficial in predicting the operative outcome.

PMID- 19584072
TI  - Emerging molecular technologies for identifying the risk of second cancers.

PMID- 19584073
TI  - Food extracts for chemoprevention: quo vadis?

PMID- 19584074
TI  - Dietary chemopreventive phytochemicals: too little or too much?
AB  - There is a large body of evidence that the consumption of fruit and vegetables
      can decrease the risk of cancer. However, the link between diet and health is
      extremely complex. Some dietary phytochemicals seem to offer protection in an
      exposure-related manner and many molecular targets and signaling pathways
      affected by phytochemicals have been discovered. Although in vitro studies have
      contributed significantly to our understanding, quite a number use concentrations
      orders of magnitude greater than those achievable in humans or toxic to normal
      tissues (exemplified by toxic concentrations of indole-3-carbinol,
      epigallocatechin-3-gallate, curcumin, and genistein for breast cells). Such
      studies may produce results that are physiologically irrelevant, thus hindering
      predictions of efficacy. Here, we argue for careful consideration to be given to
      the in vitro experimental conditions under which dietary phytochemicals are
      investigated. Design features, such as the use of appropriate nontoxic
      concentrations, extended treatment times, three-dimensional cultures, primary
      tumor cultures, and comparison of susceptibility of various cancer subtypes,
      should improve our understanding of their molecular targets. This in turn would
      facilitate predictions as to their potential usefulness in the clinic.

PMID- 19584075
TI  - Novel susceptibility loci for second primary tumors/recurrence in head and neck
      cancer patients: large-scale evaluation of genetic variants.
AB  - This study was aimed to identify novel susceptibility variants for second primary
      tumor (SPT) or recurrence in curatively treated early-stage head and neck
      squamous cell carcinoma (HNSCC) patients. We constructed a custom chip containing
      a comprehensive panel of 9,645 chromosomal and mitochondrial single nucleotide
      polymorphisms (SNP) representing 998 cancer-related genes selected by a
      systematic prioritization schema. Using this chip, we genotyped 150 early-stage
      HNSCC patients with and 300 matched patients without SPT/recurrence from a
      prospectively conducted randomized trial and assessed the association of these
      SNPs with risk of SPT/recurrence. Individually, six chromosomal SNPs and seven
      mitochondrial SNPs were significantly associated with risk of SPT/recurrence
      after adjustment for multiple comparisons. A strong gene-dosage effect was
      observed when these SNPs were combined, as evidenced by a progressively
      increasing SPT/recurrence risk as the number of unfavorable genotypes increased
      (P for trend < 1.00 x 10(-20)). Several polygenic analyses suggest an important
      role of interconnected functional network and gene-gene interaction in modulating
      SPT/recurrence. Furthermore, incorporation of these genetic markers into a
      multivariate model improved significantly the discriminatory ability over the
      models containing only clinical and epidemiologic variables. This is the first
      large-scale systematic evaluation of germ-line genetic variants for their roles
      in HNSCC SPT/recurrence. The study identified several promising susceptibility
      loci and showed the cumulative effect of multiple risk loci in HNSCC
      SPT/recurrence. Furthermore, this study underscores the importance of
      incorporating germ-line genetic variation data with clinical and risk factor data
      in constructing prediction models for clinical outcomes.

PMID- 19584076
TI  - Pilot study of oral anthocyanins for colorectal cancer chemoprevention.
AB  - Naturally occurring anthocyanins possess colorectal cancer chemopreventive
      properties in rodent models. We investigated whether mirtocyan, an anthocyanin
      rich standardized bilberry extract, causes pharmacodynamic changes consistent
      with chemopreventive efficacy and generates measurable levels of anthocyanins in
      blood, urine, and target tissue. Twenty-five colorectal cancer patients scheduled
      to undergo resection of primary tumor or liver metastases received mirtocyan 1.4,
      2.8, or 5.6 grams (containing 0.5-2.0 grams anthocyanins) daily for 7 days before
      surgery. Bilberry anthocyanins were analyzed by high performance liquid
      chromatography (HPLC) with visible or mass spectrometric detection. Proliferation
      was determined by immunohistochemistry of Ki-67 in colorectal tumor.
      Concentrations of insulin-like growth factor (IGF)-I were measured in plasma.
      Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in
      plasma, colorectal tissue, and urine, but not in liver. Anthocyanin
      concentrations in plasma and urine were roughly dose-dependent, reaching
      approximately 179 ng/gram in tumor tissue at the highest dose. In tumor tissue
      from all patients on mirtocyan, proliferation was decreased by 7% compared with
      preintervention values. The low dose caused a small but nonsignificant reduction
      in circulating IGF-I concentrations. In conclusion, repeated administration of
      bilberry anthocyanins exerts pharmacodynamic effects and generates concentrations
      of anthocyanins in humans resembling those seen in Apc(Min) mice, a model of FAP
      adenomas sensitive to the chemopreventive properties of anthocyanins. Studies of
      doses containing <0.5 gram bilberry anthocyanins are necessary to adjudge whether
      they may be appropriate for development as colorectal cancer chemopreventive
      agents.

PMID- 19584077
TI  - Chemoprevention of lung squamous cell carcinoma in mice by a mixture of Chinese
      herbs.
AB  - Antitumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies
      have shown significant chemopreventive efficacy of ATB against human esophageal
      and lung cancers. We have recently developed a new mouse model for lung squamous
      cell carcinomas (SCC). In this study, lung SCC mouse model was characterized
      using small-animal imaging techniques (magnetic resonance imaging and computed
      tomography). ATB decreased lung SCC significantly (3.1-fold; P < 0.05) and
      increased lung hyperplastic lesions by 2.4-fold (P < 0.05). This observation
      suggests that ATB can block hyperplasia from progression to SCC. ATB tissue
      distribution was determined using matrine as a marker chemical. We found that ATB
      is rapidly absorbed and then distributes to various tissues including the lung.
      These results indicate that ATB is a potent chemopreventive agent against the
      development of mouse lung SCCs.

PMID- 19584078
TI  - Topical treatment with black raspberry extract reduces cutaneous UVB-induced
      carcinogenesis and inflammation.
AB  - Light in the UVB spectrum (280-320 nm) induces a number of changes in the
      epidermis and dermis of mice and humans, resulting in a robust inflammatory
      response. A standardized black raspberry extract (BRE) has been effective in
      reducing signaling pathways commonly initiated by inflammatory stimuli. In this
      study, we determined whether this extract could reduce cutaneous UVB-induced
      inflammation and carcinogenesis. In our carcinogenesis model, female SKH-1
      hairless mice were exposed to one minimal erythemal dose of UVB thrice weekly on
      nonconsecutive days for 25 weeks. Immediately after each exposure, the mice were
      treated topically with either BRE dissolved in vehicle or with vehicle only.
      Beginning on week 19, mice treated with BRE had a significant reduction in tumor
      number and in average tumor size. This reduction correlated with a significant
      reduction in tumor-infiltrating CD3(+)foxp3(+) regulatory T-cells. In the acute
      model, mice were exposed to a single minimal erythemal dose of UVB and treated
      topically with BRE or with vehicle. At 48 hours post-UVB exposure, topical BRE
      treatment significantly reduced edema, p53 protein levels, oxidative DNA damage,
      and neutrophil activation. The ability of topical BRE to reduce acute UVB-induced
      inflammation and to decrease tumor development in a long-term model provides
      compelling evidence to explore the clinical efficacy of BRE in the prevention of
      human skin cancers.

PMID- 19584080
TI  - Maternal baicalin treatment increases fetal lung surfactant phospholipids in
      rats.
AB  - Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria
      baicalensis Georgi and has been reported to stimulate surfactant protein (SP)-A
      gene expression in human lung epithelial cell lines (H441). The aims of this
      study were to determine whether maternal baicalin treatment could increase lung
      surfactant production and induce lung maturation in fetal rats. This study was
      performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers
      were injected intraperitoneally with baicalin (5 mg/kg/day) on Day 18 of
      gestation. Two-day baicalin group mothers were injected intraperitoneally with
      baicalin (5 mg/kg/day) on Days 17 and 18 of gestation. Control group mothers were
      injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation,
      fetuses were delivered by cesarean section. Maternal treatment with 2-day
      baicalin significantly increased saturated phospholipid when compared with
      control group and total phospholipid in fetal lung tissue when compared with
      control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin
      significantly increased maternal growth hormone when compared with control group.
      Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were
      comparable among the three experimental groups. Maternal baicalin treatment
      increases pulmonary surfactant phospholipids of fetal rat lungs and the
      improvement was associated with increased maternal serum growth hormone. These
      results suggest that antenatal baicalin treatment might accelerate fetal rat lung
      maturation.

PMID- 19584079
TI  - Alpha-keto acid metabolites of naturally occurring organoselenium compounds as
      inhibitors of histone deacetylase in human prostate cancer cells.
AB  - Histone deacetylase (HDAC) inhibitors are gaining interest as cancer therapeutic
      agents. We tested the hypothesis that natural organoselenium compounds might be
      metabolized to HDAC inhibitors in human prostate cancer cells. Se-Methyl-L
      selenocysteine (MSC) and selenomethionine are amino acid components of selenium
      enriched yeast. In a cell-free system, glutamine transaminase K (GTK) and L-amino
      acid oxidase convert MSC to the corresponding alpha-keto acid, beta
      methylselenopyruvate (MSP), and L-amino acid oxidase converts selenomethionine to
      its corresponding alpha-keto acid, alpha-keto-gamma-methylselenobutyrate (KMSB).
      Although methionine (sulfur analogue of selenomethionine) is an excellent
      substrate for GTK, selenomethionine is poorly metabolized. Structurally, MSP and
      KMSB resemble the known HDAC inhibitor butyrate. We examined androgen-responsive
      LNCaP cells and androgen-independent LNCaP C4-2, PC-3, and DU145 cells and found
      that these human prostate cancer cells exhibit endogenous GTK activities. In the
      corresponding cytosolic extracts, the metabolism of MSC was accompanied by the
      concomitant formation of MSP. In MSP-treated and KMSB-treated prostate cancer
      cell lines, acetylated histone 3 levels increased within 5 hours, and returned to
      essentially baseline levels by 24 hours, suggesting a rapid, transient induction
      of histone acetylation. In an in vitro HDAC activity assay, the selenoamino
      acids, MSC and selenomethionine, had no effect at concentrations up to 2.5
      mmol/L, whereas MSP and KMSB both inhibited HDAC activity. We conclude that, in
      addition to targeting redox-sensitive signaling proteins and transcription
      factors, alpha-keto acid metabolites of MSC and selenomethionine can alter HDAC
      activity and histone acetylation status. These findings provide a potential new
      paradigm by which naturally occurring organoselenium might prevent the
      progression of human prostate cancer.

PMID- 19584081
TI  - Effective Control of Type 2 Diabetes through Antioxidant Defense by Edible Fruits
      of Diospyros peregrina.
AB  - The matured fruits of Diospyros peregrina are successfully employed by the
      traditional healers and local people of costal West Bengal, India for the
      treatment of diabetes. Present investigation was undertaken to evaluate the role
      of hydroalcoholic extract of D. peregrina (HDP) on type 2 diabetes as well as the
      augmented oxidative stresses associated with it. Oral administration of HDP at
      25, 50 and 100 mg kg(-1) body weight per day to diabetic rats was found to
      possess significant dose-dependent hypoglycemic and hypolipidemic activity. The
      diabetic rats showed lower activities of superoxide dismutase (SOD), catalase
      (CAT) and reduced glutathione (GSH) content in hepatic and renal tissues as
      compared to normal rats. The activities of SOD, CAT and GSH were found to be
      increased in extract-treated diabetic rats in selected tissues. The increased
      level of lipid peroxidation (thiobarbituric acid reactive substances) in diabetic
      rats was also found to be reverted back to near normal status in extract-treated
      groups. Thus it may be concluded that the HDP may produce its hypoglycemic effect
      through antioxidant defense mechanism.

PMID- 19584082
TI  - How well did health departments communicate about risk at the start of the Swine
      flu epidemic in 2009?
AB  - On Sunday, 26 April 2009, the secretary of the U.S. Department of Health and
      Human Services declared a public health emergency in response to the outbreak of
      H1N1 influenza (known as swine flu) in the United States. Through an analysis of
      state and local health department Web sites, we determined whether departments
      were able to provide online information to their constituents within twenty-four
      hours of the declaration. The overwhelming majority of state health departments,
      and more than half of health departments participating in the Cities Readiness
      Initiative-but only a quarter of smaller, local health departments-were
      successful in doing so.

PMID- 19584083
TI  - LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms
      and is effective even in cells from SMA patients non-responsive to valproate.
AB  - Histone deacetylase inhibitors (HDACi) are potential candidates for therapeutic
      approaches in cancer and neurodegenerative diseases such as spinal muscular
      atrophy (SMA)--a common autosomal recessive disorder and frequent cause of early
      childhood death. SMA is caused by homozygous absence of SMN1. Importantly, all
      SMA patients carry a nearly identical copy gene, SMN2, that produces only minor
      levels of correctly spliced full-length transcripts and SMN protein. Since an
      increased number of SMN2 copies strongly correlates with a milder SMA phenotype,
      activation or stabilization of SMN2 is considered as a therapeutic strategy.
      However, clinical trials demonstrated effectiveness of the HDACi valproate (VPA)
      and phenylbutyrate only in <50% of patients; therefore, identification of new
      drugs is of vital importance. Here we characterize the novel hydroxamic acid
      LBH589, an HDACi already widely used in cancer clinical trials. LBH589 treatment
      of human SMA fibroblasts induced up to 10-fold elevated SMN levels, the highest
      ever reported, accompanied by a markedly increased number of gems. FL-SMN2 levels
      were increased 2-3-fold by transcription activation via SMN2 promoter H3K9
      hyperacetylation and restoration of correct splicing via elevated hTRA2-beta1
      levels. Furthermore, LBH589 stabilizes SMN by reducing its ubiquitinylation as
      well as favouring incorporation into the SMN complex. Cytotoxic effects were not
      detectable at SMN2 activating concentrations. Notably, LBH589 also induces SMN2
      expression in SMA fibroblasts inert to VPA, in human neural stem cells and in the
      spinal cord of SMN2-transgenic mice. Hence, LBH589, which is active already at
      nanomolar doses, is a highly promising candidate for SMA therapy.

PMID- 19584084
TI  - Rac1 and Rho contribute to the migratory and invasive phenotype associated with
      somatic E-cadherin mutation.
AB  - Recent evidence suggests a close association between extracellular E-cadherin
      mutation in diffuse-type gastric carcinoma and the acquisition of a migratory
      phenotype of tumour cells. To characterize the cellular machinery that mediates
      the gain of motility of tumour cells with mutant E-cadherin, we turned to the
      small Rho GTPases Rac1 and Rho because they have been implicated in pathological
      processes including tumour cell migration and invasion. In the present study, we
      analyse the activity of Rac1 and Rho in relation to E-cadherin harbouring an in
      frame deletion of exon 8 and prove for the first time that the mutation reduces
      the ability of E-cadherin to activate Rac1 and to inhibit Rho. We provide
      evidence that the lack of Rac1 activation observed in response to mutant E
      cadherin influences the downstream signalling of Rac1, as is shown by the
      decrease in the binding of the Rac1 effector protein IQGAP1 to Rac1-GTP.
      Moreover, reduced membranous localization of p120-catenin in mutant E-cadherin
      expressing cells provides an explanation for the lack of negative regulation of
      Rho by mutant E-cadherin. Further, we show by time-lapse laser scanning
      microscopy and invasion assay that the enhanced motility and invasion associated
      with mutant E-cadherin is sensitive to the inhibition of Rac1 and Rho. Together,
      these findings present evidence that the mutation of E-cadherin influences Rac1
      and Rho activation in opposite directions and that Rac1 and Rho are involved in
      the establishment of the migratory and invasive phenotype of tumour cells that
      have an E-cadherin mutation.

PMID- 19584085
TI  - Identification of a new putative functional IL18 gene variant through an
      association study in systemic lupus erythematosus.
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role
      in chronic inflammation and autoimmune disorders. In this study, we aimed to
      determine the potential role of the IL18 gene in SLE. To define the genetic
      association of the IL18 and SLE, we have genotyped nine SNPs in an independent
      set of Spanish cases and controls. The IL18 polymorphisms were genotyped by PCR,
      using a predeveloped TaqMan allele discrimination assay. Two SNPs were still
      significant after fine mapping of the IL18 gene. The SNP (rs360719) surviving
      correction for multiple tests was genotyped in two replication cohorts from Italy
      and Argentina. After the analysis, a significance with rs360719 C-allele remained
      across the sets and after the meta-analysis (Pooled OR = 1.37, 95% CI 1.21-1.54,
      combined P = 3.8E-07, Pc = 1.16E-06). Quantitative real-time PCR was performed to
      assess IL18 mRNA expression in PBMC from subjects with different IL18 rs360719
      genotypes. We tested the effect of the IL18 rs360719 polymorphism on the
      transcription of IL18 by electrophoretic mobility shift assay and western blot.
      We found a significant increase in the relative expression of IL18 mRNA in
      individuals carrying the rs360719 C-risk allele; in addition we show that the
      polymorphism creates a binding site for the transcriptional factor OCT-1. These
      findings suggest that the novel IL18 rs360719 variant may play an important role
      in determining the susceptibility to SLE and it could be a key factor in the
      expression of the IL18 gene.

PMID- 19584086
TI  - Elucidation of the complex structure and origin of the human trypsinogen locus
      triplication.
AB  - One of the causes of chronic pancreatitis is the duplication and triplication of
      a approximately 605 kb segment containing the trypsinogen locus. Employing array
      comparative genomic hybridization, we fully characterized the triplication copy
      number mutation (CNM) and found it to be part of a complex rearrangement that
      also contains a triplicated approximately 137 kb segment and 21 bp sequence
      tract. This triplication allele therefore constitutes a gain of two tandemly
      arranged composite duplication blocks, each comprising a copy of the
      approximately 605 kb segment, a copy of the inverted approximately 137 kb segment
      and a copy of the inverted 21 bp sequence tract. As such, it represents the first
      characterization of a human complex triplication CNM at the DNA sequence level.
      All triplications and duplications identified were found to arise from a common
      founder chromosome. A two-step process is proposed for the generation of this
      highly unusual triplication CNM. Thus, the first composite duplication block is
      envisaged to have been generated by break-induced serial replication slippage
      during mitosis. This duplication would have provided the sequence homology
      required to promote non-allelic homologous recombination (NAHR) during meiosis
      which would then, in a second step, have generated the complex triplication
      allele. Our data provide support for the view that many human germline copy
      number variants arise through replication-based mechanisms during the premeiotic
      mitotic divisions of germ cells. The low copy repeats thereby generated could
      then serve to promote NAHR during meiosis, giving rise to amplified DNA sequences
      which would themselves predispose to further recombinational events during both
      mitosis and meiosis.

PMID- 19584087
TI  - Generation of an epigenetic signature by chronic hypoxia in prostate cells.
AB  - Increasing levels of tissue hypoxia have been reported as a natural feature of
      the aging prostate gland and may be a risk factor for the development of prostate
      cancer. In this study, we have used PwR-1E benign prostate epithelial cells and
      an equivalently aged hypoxia-adapted PwR-1E sub-line to identify phenotypic and
      epigenetic consequences of chronic hypoxia in prostate cells. We have identified
      a significantly altered cellular phenotype in response to chronic hypoxia as
      characterized by increased receptor-mediated apoptotic resistance, the induction
      of cellular senescence, increased invasion and the increased secretion of IL-1
      beta, IL6, IL8 and TNFalpha cytokines. In association with these phenotypic
      changes and the absence of HIF-1 alpha protein expression, we have demonstrated
      significant increases in global levels of DNA methylation and H3K9 histone
      acetylation in these cells, concomitant with the increased expression of DNA
      methyltransferase DMNT3b and gene-specific changes in DNA methylation at key
      imprinting loci. In conclusion, we have demonstrated a genome-wide adjustment of
      DNA methylation and histone acetylation under chronic hypoxic conditions in the
      prostate. These epigenetic signatures may represent an additional mechanism to
      promote and maintain a hypoxic-adapted cellular phenotype with a potential role
      in tumour development.

PMID- 19584092
TI  - Siva1 is a XIAP-interacting protein that balances NFkappaB and JNK signalling to
      promote apoptosis.
AB  - XIAP is known as a potent inhibitor of apoptosis, but in addition is involved in
      cellular signalling, including the NFkappaB, JNK and TGFbeta pathways. Our search
      for XIAP-interacting partners led us to Siva1, a proapoptotic protein that is
      known to play a role in T-cell apoptosis through a caspase-dependent
      mitochondrial pathway. The interaction sites between XIAP and Siva1 were mapped
      to the RING domain of XIAP and the N-terminal, SAH-containing and death-homology
      region-containing domains of Siva1. Co-immunoprecipitation experiments showed
      that XIAP, Siva1 and TAK1 form a ternary complex in Jurkat T cells. Reporter-gene
      analysis revealed that Siva1 inhibits XIAP- and TAK1-TAB1-mediated NFkappaB
      activation. By contrast, Siva1 increased XIAP- and TNFalpha-mediated AP1 activity
      and prolonged TNFalpha-induced JNK activation, whereas knock down of Siva1
      resulted in reduced JNK activation. This suggests that Siva1 differentially
      modulates signalling by JNK and NFkappaB and shifts the balance between these
      pathways towards enhanced JNK activation, a situation that promotes apoptosis.
      Ectopically expressed Siva1 increased caspase-3 activity, which was inhibited by
      XIAP in a ubiquitin-ligase-dependent manner. In line with this, Siva1 was lysine
      48-linked polyubiquitylated by XIAP. Our findings suggest that, via physical
      interaction with XIAP and TAK1, Siva1 diminishes NFkappaB and enhances JNK
      activity to favour apoptosis.

PMID- 19584093
TI  - AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of
      TRAF2.
AB  - AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2; also
      known as JTV-1) was first identified as p38 in a macromolecular protein complex
      that consisted of nine different aminoacyl-tRNA synthetases and two other
      auxiliary factors. AIMP2 also plays pivotal roles in the regulation of cell
      proliferation and death. Although AIMP2 was previously shown to augment TNFalpha
      induced cell death, its working mechanism in this signal pathway was not
      understood. Here, we investigate the functional significance and mode of action
      of AIMP2 in TNFalpha signaling. TNFalpha-induced cell death was compromised in
      AIMP2-deficient or -suppressed cells and exogenous supplementation of AIMP2
      augmented apoptotic sensitivity to TNFalpha signaling. This activity was
      confirmed by the AIMP2-dependent increase of IkappaB and suppression of NFkappaB.
      We found binding of AIMP2 to TRAF2, a key player in the TNFalpha signaling
      pathway. AIMP2 augmented the association of an E3 ubiquitin ligase, c-IAP1, with
      TRAF2, causing ubiquitin-dependent degradation of TRAF2. These findings suggest
      that AIMP2 can mediate the pro-apoptotic activity of TNFalpha via the
      downregulation of TRAF2 expression.

PMID- 19584095
TI  - Obscurin determines the architecture of the longitudinal sarcoplasmic reticulum.
AB  - The giant protein obscurin is thought to link the sarcomere with the sarcoplasmic
      reticulum (SR). The N-terminus of obscurin interacts with the M-band proteins
      titin and myomesin, whereas the C-terminus mediates interactions with ankyrin
      proteins. Here, we investigate the importance of obscurin for SR architecture and
      organization. Lack of obscurin in cross-striated muscles leads to changes in
      longitudinal SR architecture and disruption of small ankyrin-1.5 (sAnk1.5)
      expression and localization. Changes in SR architecture in obscurin knockout mice
      are also associated with alterations in several SR or SR-associated proteins,
      such as ankyrin-2 and beta-spectrin. Finally, obscurin knockout mice display
      centralized nuclei in skeletal muscles as a sign of mild myopathy, but have
      normal sarcomeric structure and preserved muscle function.

PMID- 19584094
TI  - Dynamic localization of G proteins in Dictyostelium discoideum.
AB  - Extracellular stimuli exert their effects on eukaryotic cells via serpentine G
      protein-coupled receptors and mediate a vast number of physiological responses.
      Activated receptors stimulate heterotrimeric G-proteins, consisting of three
      subunits, alpha, beta and gamma. In Dictyostelium discoideum, cAMP binds to the
      cAMP receptor cAR1, which is coupled to the heterotrimer containing the Galpha2
      subunit. These studies provide in vivo evidence as to how receptors influence the
      localization of the G-protein complex prior to and after ligand binding. Previous
      work has shown that the state of the heterotrimer could be monitored by changes
      in fluorescence (or Forster) resonance energy transfer (FRET) between the alpha2-
      and beta-subunits of D. discoideum. We now report the kinetics of G-protein
      activation as a loss of FRET prior to and after cAMP addition by using total
      internal reflection fluorescence microscopy (TIRFM). We also performed
      photobleaching experiments to measure G-protein recovery times. Our data show
      that inactive and active G-proteins cycle between the cytosol and plasma
      membrane. These data suggest that cAR1 activation slows the membrane dissociation
      ('off') rate of the alpha2 subunit, while simultaneously promoting betagamma
      subunit dissociation.

PMID- 19584096
TI  - Integrins mediate their unconventional, mechanical-stress-induced secretion via
      RhoA and PINCH in Drosophila.
AB  - During the epithelium remodelling such as the flattening of the Drosophila
      follicular epithelium, the alpha-integrin subunits are unconventionally secreted
      through a dGRASP-dependent route that is built de novo. The biogenetic process
      starts with the upregulation of a small subset of targeted mRNAs, including
      dgrasp. Here, we show that dgrasp mRNA upregulation is triggered by the tension
      of the underlying oocyte and by applied external forces at the basal side of the
      follicular epithelium. We show that integrins are also involved in dgrasp mRNA
      upregulation and the epithelium remodelling. Tension leads to the recruitment of
      RhoA to the plasma membrane, where it participates in its remodelling. The LIM
      protein PINCH can cycle to the nucleus and is involved in dgrasp mRNA
      upregulation. We propose that integrins are involved in triggering the biogenesis
      of their own unconventional secretion route that they use to strengthen adhesion
      and ensure epithelial integrity at the next stages of development, perhaps by
      acting as mechanosensors of the underlying tension through RhoA and PINCH.

PMID- 19584098
TI  - Endonuclease-sensitive regions of human spermatozoal chromatin are highly
      enriched in promoter and CTCF binding sequences.
AB  - During the haploid phase of mammalian spermatogenesis, nucleosomal chromatin is
      ultimately repackaged by small, highly basic protamines to generate an extremely
      compact, toroidal chromatin architecture that is critical to normal spermatozoal
      function. In common with several species, however, the human spermatozoon retains
      a small proportion of its chromatin packaged in nucleosomes. As nucleosomal
      chromatin in spermatozoa is structurally more open than protamine-packaged
      chromatin, we considered it likely to be more accessible to exogenously applied
      endonucleases. Accordingly, we have used this premise to identify a population of
      endonuclease-sensitive DNA sequences in human and murine spermatozoa. Our results
      show unequivocally that, in contrast to the endonuclease-resistant sperm
      chromatin packaged by protamines, regions of increased endonuclease sensitivity
      are closely associated with gene regulatory regions, including many promoter
      sequences and sequences recognized by CCCTC-binding factor (CTCF). Similar
      differential packaging of promoters is observed in the spermatozoal chromatin of
      both mouse and man. These observations imply the existence of epigenetic marks
      that distinguish gene regulatory regions in male germ cells and prevent their
      repackaging by protamines during spermiogenesis. The ontology of genes under the
      control of endonuclease-sensitive regulatory regions implies a role for this
      phenomenon in subsequent embryonic development.

PMID- 19584100
TI  - Acinar cell carcinoma with prominent intraductal growth pattern: case report and
      review of the literature.
AB  - Acinar cell carcinoma of the pancreas is rare, accounting for less than 1% of
      carcinomas arising in the exocrine pancreas. Patients are typically between the
      fifth and seventh decade of life and show a 2:1 male predominance. Symptoms tend
      to be nonspecific, and approximately 50% of the patients have metastases at the
      time of presentation. There have been recent case reports of acinar cell
      carcinoma showing both intraductal and/or papillary patterns of growth that could
      potentially be mistaken for intraductal neoplasia. The cases reported up to date
      presented as solitary nodules. The authors describe the first case of acinar cell
      carcinoma with both intraductal and tubuloglandular growth diffusely involving
      the pancreas. In addition, the authors review the published cases reporting
      acinar cell carcinoma with intraductal and/or papillary growth patterns.

PMID- 19584099
TI  - Functional involvement of central cholinergic circuits and visual hallucinations
      in Parkinson's disease.
AB  - Visual hallucinations (VHs) represent a frequent and disturbing complication of
      Parkinson's disease. Evidence suggests that VH can be related to central
      cholinergic dysfunction. Short-latency afferent inhibition (SAI) technique gives
      the opportunity to test an inhibitory cholinergic circuit in the human cerebral
      motor cortex. This inhibition of motor-evoked potentials can be observed when
      transcranial magnetic stimulation is delivered with a delay ranging from 2 to 8
      ms, after a peripheral nerve afferent input has reached the somatosensory cortex.
      We applied SAI technique in 10 non-demented patients with Parkinson's disease
      with VHs, in 12 non-demented patients with Parkinson's disease without VHs (NVH
      pts) and in 11 age-matched normal controls. All patients with Parkinson's disease
      underwent a battery of neuropsychological tests to assess frontal and
      visuospatial functions, memory and attention. SAI was significantly reduced in
      patients with VHs compared with controls and patients without VHs.
      Neuropsychological examination showed a mild cognitive impairment in 16 out of 22
      patients with Parkinson's disease. In addition, we found that in our patients
      with VHs, performance of some tasks evaluating visuospatial functions and
      attentional/frontal lobe functions was significantly more impaired than in
      patients without VHs. SAI abnormalities, presence of VH and neuropsychological
      results strongly support the hypothesis of cholinergic dysfunction in some
      patients with Parkinson's disease, who will probably develop a dementia. A follow
      up study of our patients is required to verify whether SAI abnormalities can
      predict a future severe cognitive decline. Moreover, SAI can also be very useful
      to follow-up the efficacy of anti-cholinesterase therapies.

PMID- 19584101
TI  - Chemical synthesis of 6(GlcNAc)- and 6(Gal)-O-sulfated SiaLe(X) tetrasaccharides
      in spacer-armed form.
AB  - Practical synthesis of tetrasaccharide sulfates, 6((GlcNAc))-O-Su-SiaLe(X)
      OCH(2)CH(2)CH(2)NH(2) and 6((Gal))-O-Su-SiaLe(X)-OCH(2)CH(2)CH(2)NH(2) (Su(
      )SO(3)H), selectin ligands, and leu- kocyte trafficking agents is presented. Both
      sulfates were synthesized starting from the same precursor, protected SiaLe(x),
      by the conventional procedures of carbohydrate chemistry. The sulfated SiaLe(x)
      derivative was modified at the spacer group to give 6((Gal))-O-Su-SiaLe(x)-
      OCH(2)CH(2)CH(2)NH-COCH(2)CH(2)C[triple bond]CH, convenient for "click chemistry"
      mode conjugation with an azido carrier, particularly, for the synthesis of an
      immunogen.

PMID- 19584097
TI  - Clusters and superclusters of phased small RNAs in the developing inflorescence
      of rice.
AB  - To address the role of small regulatory RNAs in rice development, we generated a
      large data set of small RNAs from mature leaves and developing roots, shoots, and
      inflorescences. Using a spatial clustering algorithm, we identified 36,780
      genomic groups of small RNAs. Most consisted of 24-nt RNAs that are expressed in
      all four tissues and enriched in repeat regions of the genome; 1029 clusters were
      composed primarily of 21-nt small RNAs and, strikingly, 831 of these contained
      phased RNAs and were preferentially expressed in developing inflorescences.
      Thirty-eight of the 24-mer clusters were also phased and preferentially expressed
      in inflorescences. The phased 21-mer clusters derive from nonprotein coding,
      nonrepeat regions of the genome and are grouped together into superclusters
      containing 10-46 clusters. The majority of these 21-mer clusters (705/831) are
      flanked by a degenerate 22-nt motif that is offset by 12 nt from the main phase
      of the cluster. Small RNAs complementary to these flanking 22-nt motifs define a
      new miRNA family, which is conserved in maize and expressed in developing
      reproductive tissues in both plants. These results suggest that the biogenesis of
      phased inflorescence RNAs resembles that of tasiRNAs and raise the possibility
      that these novel small RNAs function in early reproductive development in rice
      and other monocots.

PMID- 19584102
TI  - Clinical manifestations, antibiotic susceptibility and molecular analysis of
      Mycobacterium kansasii isolates from a university hospital in Taiwan.
AB  - OBJECTIVES: Mycobacterium kansasii causes a variety of infections. Although
      previous reports on the prognosis of antimicrobial therapy have been mostly
      satisfactory, problems involving treatment failure or relapse have been
      encountered. The purpose of this study was to establish a relationship between
      the clinical treatment outcomes of M. kansasii infections and bacterial drug
      susceptibility, and their clonality. METHODS: A total of 37 M. kansasii clinical
      isolates and clinical information on 34 patients were retrospectively collected
      in a tertiary medical centre in Taiwan. Bacterial drug susceptibility was
      determined by the microdilution method. The phylogenetic relationship was
      analysed by PFGE analysis. RESULTS: Results of PFGE typing revealed a major
      cluster (cluster I) and eight other divergent patterns. Two/three strains leading
      to treatment failure were also multidrug resistant and belonged to cluster I.
      CONCLUSIONS: A relationship between high drug resistance and genetic relatedness
      of some M. kansasii strains was established. This was associated with clinical
      treatment failure.

PMID- 19584103
TI  - Imipenem underdosing as a cause of persistent neutropenic fever?

PMID- 19584104
TI  - Treatment and prevention of Candida albicans biofilms with caspofungin in a novel
      central venous catheter murine model of candidiasis.
AB  - OBJECTIVES: We sought to develop a novel model of central venous catheter (CVC)
      associated candidiasis in mice and to use this model to examine the efficacy of
      caspofungin to treat and prevent Candida albicans biofilms in vivo. METHODS: We
      used catheterized mice, commercially available from the National Cancer
      Institute, to form C. albicans biofilms inside CVCs. Once the model was
      developed, we examined the efficacy of caspofungin for the treatment of preformed
      biofilms and for the prevention of C. albicans biofilm formation. RESULTS: We
      developed a relatively simple murine model of CVC-associated candidiasis that
      minimized the number of manipulations necessary for in vivo biofilm formation. C.
      albicans biofilms formed in vivo display structural features similar to those
      observed for models of in vitro- and other in vivo-formed biofilms. Following
      model development, 0.25 microg/mL of caspofungin was instilled in the catheter to
      treat preformed biofilms. The results indicated that caspofungin treatment
      significantly reduced biofilm fungal load in the catheters and dissemination to
      kidneys compared with untreated controls. In a second set of experiments
      catheters were pre-treated by filling with 60 microg/mL of caspofungin before
      challenge with C. albicans via the CVC. Again, the results indicated a
      significant reduction in biofilm fungal load and dissemination to kidneys
      compared with untreated controls. CONCLUSIONS: We have developed a novel model of
      CVC-associated candidiasis in mice. Using this model we demonstrate the efficacy
      of caspofungin for the treatment and prevention of C. albicans biofilms in vivo.

PMID- 19584105
TI  - Developments in outpatient parenteral antimicrobial therapy (OPAT) for Gram
      positive infections in Europe, and the potential impact of daptomycin.
AB  - Parenteral antimicrobial therapy is traditionally offered in the inpatient
      setting in many parts of the world. In the USA, the past three decades have seen
      an unprecedented increase in the delivery of these therapies in the non-inpatient
      setting, and outpatient parenteral antibiotic therapy (OPAT) is now an
      established standard of care in North America. However, the uptake of OPAT within
      Europe has been more gradual, owing to a number of clinical, fiscal, logistical
      and cultural considerations. In particular, physicians who are not currently
      engaged in OPAT programmes frequently cite concerns over patient safety as a
      major barrier. However, where OPAT programmes have been established, high levels
      of satisfaction are reported by both patients and physicians, suggesting that
      many anxieties concerning the introduction of OPAT stem from a lack of patient
      and physician education regarding the key potential benefits associated with
      OPAT. As the burden of serious Gram-positive infections grows, so does the need
      to offer clinicians, administrators and patients alternative treatment programmes
      that are equally effective and safe compared with inpatient treatment, while
      promoting optimal use of limited healthcare resources. This article will review
      the European experience of OPAT, discussing the associated benefits and the
      potential antibiotic options, with an emphasis on the evolving experience with
      daptomycin.

PMID- 19584106
TI  - Molecular characterization of macrolide resistance determinants [erm(B) and
      mef(A)] in Streptococcus pneumoniae and viridans group streptococci (VGS)
      isolated from adult patients with cystic fibrosis (CF).
AB  - OBJECTIVES: Although long-term use of azithromycin has shown a significant
      clinical improvement for patients with cystic fibrosis (CF), its long-term effect
      on the susceptibility of commensal flora within CF airways has not yet been
      examined. We therefore suggest that long-term use of azithromycin increases
      macrolide resistance in commensal streptococci. METHODS: Erythromycin
      susceptibility in naturally colonizing viridans group streptococci (VGS) was
      characterized, as well as macrolide resistance gene determinants through sequence
      analysis, in pneumococci (n = 15) and VGS [n = 84; i.e. Streptococcus salivarius
      (n = 30), Streptococcus mitis (n = 17), Streptococcus sanguinis (n = 11),
      Streptococcus oralis (n = 10), Streptococcus parasanguinis (n = 6), Streptococcus
      gordonii (n = 3), Streptococcus infantis (n = 3), Streptococcus cristatus (n =
      2), Streptococcus anginosus (n = 1) and Streptococcus australis (n = 1)] isolated
      from sputum from 24 adult CF patients, who were on oral azithromycin therapy for
      at least the previous 7 months. RESULTS: Almost three-quarters of isolates (74;
      74.7%) were resistant to erythromycin, whilst a further 15 (15.2%) had reduced
      susceptibility, leaving only 10 (10.1%) isolates susceptible to erythromycin. The
      majority (89.8%) were not susceptible to erythromycin, as demonstrated by
      possession of the erm(B) gene in 25/99 (25.3%), the mef(A) gene in 1/99 (1.0%),
      the mef(E) gene in 75/99 (75.8%) and both erm(B) and mef(E) genes simultaneously
      in 11/99 (11.1%). These results indicate that genotypic resistance for macrolides
      is common in VGS in adult CF patients, with efflux being over three times more
      frequent. CONCLUSIONS: Long-term treatment with azithromycin in CF patients may
      reduce antibiotic susceptibility in commensal VGS, where these organisms may
      potentially act as a reservoir of macrolide resistance determinants for newly
      acquired and antibiotic-susceptible pathogens.

PMID- 19584107
TI  - Survival among nocturnal home haemodialysis patients compared to kidney
      transplant recipients.
AB  - BACKGROUND: Kidney transplantation is the gold standard renal replacement
      therapy. Nocturnal haemodialysis (NHD) is an intensive dialysis modality (6-8
      h/session, 3-7 sessions/week) associated with a significant improvement of
      clinical and biochemical parameters compared to conventional dialysis. To date,
      no studies have compared survival in patients treated with NHD and kidney
      transplantation. METHODS: Using data from two regional NHD programmes and the
      USRDS from 1994 to 2006, we performed a matched cohort study comparing survival
      between NHD and deceased and living donor kidney transplantation (DTX and LTX) by
      randomly matching NHD patients to transplant recipients in a 1:3:3 ratio. The
      independent association of treatment modality with survival was determined using
      Cox multivariate regression. RESULTS: The total study population consisted of 177
      NHD patients matched to 1062 DTX and LTX recipients (total 1239 patients)
      followed for a maximum of 12.4 years. During the follow-up period, the proportion
      of deaths among NHD, DTX and LTX patients was 14.7%, 14.3% and 8.5%, respectively
      (P = 0.006). We found no difference in the adjusted survival between NHD and DTX
      (HR 0.87, 95% CI 0.50-1.51; NHD reference group), while LTX survival was better
      (HR 0.51, 95% CI 0.28-0.91). CONCLUSIONS: These results indicate that NHD and DTX
      survival is comparable, and suggest that this intensive dialysis modality may be
      a bridge to transplantation or even a suitable alternative in the absence of LTX
      in the current era of growing transplant waiting lists and organ shortage.

PMID- 19584111
TI  - Patients and doctors are asked to report antivirals' side effects as swine flu
      spreads.

PMID- 19584108
TI  - Proteomic analysis of murine Piwi proteins reveals a role for arginine
      methylation in specifying interaction with Tudor family members.
AB  - In germ cells, Piwi proteins interact with a specific class of small noncoding
      RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that
      represses transposable elements, thus safeguarding germ cell genomes. Basic
      models describe the overall operation of piRNA pathways. However, the protein
      compositions of Piwi complexes, the critical protein-protein interactions that
      drive small RNA production and target recognition, and the precise molecular
      consequences of conserved localization to germline structures, call nuage,
      remains poorly understood. We purified the three murine Piwi family proteins,
      MILI, MIWI, and MIWI2, from mouse germ cells and characterized their interacting
      protein partners. Piwi proteins were found in complex with PRMT5/WDR77, an enzyme
      that dimethylates arginine residues. By immunoprecipitation with specific
      antibodies and by mass spectrometry, we found that Piwi proteins are arginine
      methylated at conserved positions in their N termini. These modifications are
      essential to direct complex formation with specific members of the Tudor protein
      family. Recognition of methylarginine marks by Tudor proteins can drive the
      localization of Piwi proteins to cytoplasmic foci in an artificial setting,
      supporting a role for this interaction in Piwi localization to nuage, a
      characteristic that correlates with proper operation of the piRNA pathway and
      transposon silencing in multiple organisms.

PMID- 19584113
TI  - Access to antimalarial therapy: accurate diagnosis is essential to achieving long
      term goals.

PMID- 19584116
TI  - Does night-time transpiration contribute to anisohydric behaviour in a Vitis
      vinifera cultivar?
AB  - The hypothesis that vines of the Semillon wine grape variety show anisohydric
      behaviour was tested, i.e. that tissue hydration is unstable under fluctuating
      environmental conditions. Stomatal conductance and transpiration rates from
      leaves were measured during the day and at night. Leaf water potential (Psi(l))
      in Semillon was negatively correlated to vapour pressure deficit (VPD) both
      predawn and during the day. Furthermore, Psi(l) fell to significantly lower
      values than in any of the nine other varieties examined. Night-time values of
      stomatal conductance (g(n)) and transpiration (E(n)) in Semillon were up to four
      times higher than in other varieties; plants enclosed in plastic bags overnight
      to reduce E(n) resulted in better plant-soil equilibration so that predawn Psi(l)
      in Semillon was the same as in Grenache. These data indicate that the hypothesis
      is supported, and that night-time transpiration contributes significantly to the
      low Psi(l) values in Semillon during warm, dry nights. The other contributing
      factor is daytime stomatal conductance (g(day)), which in Semillon leaves was
      higher than in other varieties, although the decline in g(day) with increasing
      VPD was greater in Semillon than in Shiraz or Grenache. The high values of g(day)
      were associated with high rates of transpiration (E(day)) by Semillon through a
      day when VPD reached 4.5 kPa. When compared to other varieties, Semillon was not
      unusual in terms of root length density, stomatal density, xylem sap abscisic
      acid, or leaf electrolyte leakage. Night-time and daytime water loss and
      insufficient stomatal regulation therefore account for the tendency to
      anisohydric behaviour shown by Semillon.

PMID- 19584117
TI  - RACK1 is a negative regulator of ABA responses in Arabidopsis.
AB  - Receptor for Activated C Kinase 1 (RACK1) is viewed as a versatile scaffold
      protein in mammals. The protein sequence of RACK1 is highly conserved in
      eukaryotes. However, the function of RACK1 in plants remains poorly understood.
      Accumulating evidence suggested that RACK1 may be involved in hormone responses,
      but the precise role of RACK1 in any hormone signalling pathway remains elusive.
      Molecular and genetic evidence that Arabidopsis RACK1 is a negative regulator of
      ABA responses is provided here. It is shown that three RACK1 genes act
      redundantly to regulate ABA responses in seed germination, cotyledon greening and
      root growth, because rack1a single and double mutants are hypersensitive to ABA
      in each of these processes. On the other hand, plants overexpressing RACK1A
      displayed ABA insensitivity. Consistent with their proposed roles in seed
      germination and early seedling development, all three RACK1 genes were expressed
      in imbibed, germinating and germinated seeds. It was found that the ABA
      responsive marker genes, RD29B and RAB18, were up-regulated in rack1a mutants.
      Furthermore, the expression of all three RACK1 genes themselves was down
      regulated by ABA. Consistent with the view that RACK1 negatively regulates ABA
      responses, rack1a mutants lose water significantly more slowly from the rosettes
      and are hypersensitive to high concentrations of NaCl during seed germination. In
      addition, the expression of some putative RACK1-interacting, ABA-, or abiotic
      stress-regulated genes was mis-regulated in rack1a rack1b double mutants in
      response to ABA. Taken together, these findings provide compelling evidence that
      RACK1 is a critical, negative regulator of ABA responses.

PMID- 19584118
TI  - Immune system-tumour efficiency ratio as a new oncological index for radiotherapy
      treatment optimization.
AB  - A dynamical system model for tumour-immune system interaction together with a
      method to mimic radiation therapy are proposed. A large population of virtual
      patients is simulated following an ideal radiation treatment. A characteristic
      parameter, the immune system-tumor efficiency ratio (ISTER) is introduced. ISTER
      dependence of treatment success and other features are studied. Radiotherapy
      treatment dose optimization, following ALARA (As Low As Reasonably Achievable)
      criterion, as well as a patient classification are drawn from the statistics
      results.

PMID- 19584119
TI  - Genomic approaches for designing durum wheat ready for climate change with a
      focus on drought.
AB  - Climate change is projected to have a significant impact on temperature and
      precipitation profiles in the Mediterranean basin. The incidence and severity of
      drought will become commonplace and this will reduce the productivity of rain-fed
      crops such as durum wheat. Genetic diversity is the material basis for crop
      improvement and plant breeding has exploited naturally occurring variation to
      deliver cultivars with improved resistance to abiotic stresses. The coupling of
      new genomic tools, technologies, and resources with genetic approaches is
      essential to underpin wheat breeding through marker-assisted selection and hence
      mitigate climate change. Improvements in crop performance under abiotic stresses
      have primarily targeted yield-related traits and it is anticipated that the
      application of genomic technologies will introduce new target traits for
      consideration in wheat breeding for resistance to drought. Many traits relating
      to the plant's response and adaptation to drought are complex and multigenic, and
      quantitative genetics coupled with genomic technologies have the potential to
      dissect complex genetic traits and to identify regulatory loci, genes and
      networks. Full realization of our abilities to manipulate metabolism,
      transduction pathways, and transcription factors for crop improvement ultimately
      relies on our basic understanding of the regulation of plant networks at all
      levels of function.

PMID- 19584120
TI  - Physical effects of soil drying on roots and crop growth.
AB  - The nature and effect of the stresses on root growth in crops subject to drying
      is reviewed. Drought is a complex stress, impacting on plant growth in a number
      of interacting ways. In response, there are a number of ways in which the growing
      plant is able to adapt to or alleviate these stresses. It is suggested that the
      most significant opportunity for progress in overcoming drought stress and
      increasing crop yields is to understand and exploit the conditions in soil by
      which plant roots are able to maximize their use of resources. This may not be
      straightforward, with multiple stresses, sometimes competing functions of roots,
      and conditions which impact upon roots very differently depending upon what soil,
      what depth or what stage of growth the root is at. Several processes and the
      interaction between these processes in soil have been neglected. It is our view
      that drought is not a single, simple stress and that agronomic practice which
      seeks to adapt to climate change must take account of the multiple facets of both
      the stress induced by insufficient water as well as other interacting stresses
      such as heat, disease, soil strength, low nutrient status, and even hypoxia. The
      potential for adaptation is probably large, however. The possible changes in
      stress as a result of the climate change expected under UK conditions are
      assessed and it appears possible that wet warm winters will impact on root growth
      as much if not more than dry warm summers.

PMID- 19584121
TI  - Unravelling the regulatory mechanisms that modulate the MEP pathway in higher
      plants.
AB  - The methyl-D-erythritol 4-phosphate pathway is responsible for the biosynthesis
      of a substantial number of natural compounds of biological and biotechnological
      importance. In recent years, this pathway has become an obvious target to develop
      new herbicides and antimicrobial drugs. In addition, the production of a variety
      of compounds of medical and agricultural interest may be possible through the
      genetic manipulation of this pathway. To this end, a complete understanding of
      the molecular mechanisms that regulate this pathway is of tremendous importance.
      Recent data have accumulated that show some of the multiple mechanisms that
      regulate the methyl-D-erythritol 4-phosphate pathway in plants. In this review we
      will describe some of these and discuss their implications. It has been
      demonstrated that 1-deoxy-D-xylulose-5-phosphate synthase (DXS), the first enzyme
      of this route, plays a major role in the overall regulation of the pathway. A
      small gene family codes for this enzyme in most of the plants which have been
      analysed so far, and the members of these gene families belong to different
      phylogenetic groups. Each of these genes exhibits a distinct expression pattern,
      suggesting unique functions. One of the most interesting regulatory mechanisms
      recently described for this pathway is the post-transcriptional regulation of the
      level of DXS and DXR proteins. In the case of DXS, this regulation appears
      conserved among plants, supporting its importance. The evidence accumulated
      suggests that this regulation might link the activity of this pathway with the
      plant's physiological conditions and the metabolic demand for the final products
      of this route.

PMID- 19584123
TI  - High medical co-morbidity and family history of dementia is associated with lower
      cognitive function in older patients.
AB  - BACKGROUND: Risk factors for cognitive decline in ageing are multifactorial,
      including medical co-morbidities and familial genetic risk. OBJECTIVES: To assess
      the effect of medical co-morbidity and family history of dementia on cognitive
      performance in older outpatients of family practitioners. METHODS: Analysis of
      535 outpatients from 11 practices aged 65 and older, without a diagnosis of
      dementia. Information on medical co-morbidities, family history of dementia and
      cognitive test data were obtained. RESULTS: Patients were classified into high or
      low medical co-morbidities (<7 versus >8) and positive or negative family history
      of dementia. After controlling for age, education, gender and depression, global
      cognitive test scores, as well as memory, executive function, spatial ability and
      attention were significantly lower for persons having a high number of medical co
      morbidities. Cognitive test scores were not significantly different for persons
      with or without a family history of dementia. A significant interaction between
      medical co-morbidities and family history of dementia was observed for the global
      cognitive score, executive function and spatial ability. Those persons with a
      high number of medical co-morbidities and positive family history of dementia had
      the lowest performance. Separate regression analysis assessing individual disease
      risk factors (e.g. hypertension and diabetes) did not find any relationship
      between specific medical variables and cognitive test scores for any of the
      subgroups. CONCLUSIONS: A high number of medical co-morbidities in addition to a
      reported family history of dementia are particularly detrimental to cognitive
      performance in elderly non-demented family practice patients.

PMID- 19584124
TI  - Commentary: A new dawn for genetic epidemiology?

PMID- 19584122
TI  - The association between GP and patient ratings of quality of care at outpatient
      clinics.
AB  - BACKGROUND: GPs and patients are frequently asked to evaluate mental health care,
      but studies including evaluations from both groups are rare. OBJECTIVE: To assess
      the association between GPs' and patients' assessment of mental health outpatient
      clinic in Norway and identify important health care predictors for patient and GP
      satisfaction with the clinics. METHODS: Two cross-sectional national surveys were
      carried out: survey of GPs in 2006 and patients in 2007 evaluating outpatient
      clinics at 69 community mental health centres in Norway. A total of 2009 GPs and
      9001 outpatients assessed the clinics by means of a postal questionnaire. Main
      outcome measures were correlations between GP and patient ratings of the
      outpatient clinics at the clinic level and health care predictors for patient
      satisfaction and GP satisfaction with the clinics. RESULTS: Clinic scores for
      GPs' and patients' assessment of waiting time were moderate to highly correlated
      (0.65), while clinic scores for GP and patient satisfaction had a lower but
      significant positive association (0.37). Significant positive correlations
      between clinic scores for GP and patients ratings were found for 38 of the 48
      associations tested. The most important predictors for patient satisfaction with
      the clinics were interaction with the clinician (beta: 0.23) and being met with
      politeness and respect at the clinic (beta: 0.19), while the most important
      predictors for GP satisfaction with the clinics were perceived competence (beta:
      0.25), rejection of referrals (beta: -0.17) and waiting time for patients (beta: 
      0.16). CONCLUSIONS: A consistent positive association between GP and patient
      ratings at the clinic level was identified. Mental health services aiming at
      improving GP and patient satisfaction should be sensitive to the fact that the
      two groups prioritize different health care factors.

PMID- 19584125
TI  - Correlates of environmental factors and human plague: an ecological study in
      Vietnam.
AB  - BACKGROUND: Human plague caused by Yersinia pestis remains a public health threat
      in endemic countries, because the disease is associated with increased risk of
      mortality and severe economic and social consequences. During the past 10 years,
      outbreaks of plague have occasionally occurred in Vietnam's Central Highlands
      region. The present study sought to describe and analyse the occurrence of plague
      and its association with ecological factors. METHODS: The study included all 510
      communes of the Central Highlands region (with a total population of
      approximately 4 million) where 95% of incidence of plague cases in Vietnam had
      been reported from 1997 through 2002. Plague was clinically ascertained by using
      a standard protocol by WHO. Data on domestic fleas and rodents were obtained by
      using traps and periodic surveillance in accordance with the WHO guidelines.
      Temperature, duration of sunshine, rainfall and humidity were recorded as monthly
      averages by local meteorological stations. The association between these
      ecological factors and plague was assessed by using the Poisson regression model.
      RESULTS: From 1997 through 2002, 472 cases of plague were reported, of whom 24
      (5.1%) died. The incidence of plague peaked during the dry season, with
      approximately 63% of cases occurring from February through April. The risk of
      plague occurrence was associated with an increased monthly flea index (RR and 95%
      CI: 1.93; 1.61-2.33 for months with the flea index >1) and increased rodent
      density (RR 1.23; 1.15-1.32 per each 3% increase in density). Moreover, the risk
      of plague increased during the dry season (RR 2.07; 1.64-2.62), when rainfall
      fell <10 mm (RR 1.44; 1.17-1.77). CONCLUSIONS: These data suggest that the flea
      index, rodent density and rainfall could be used as ecological indicators of
      plague risk in Vietnam. The data also suggest that the occurrence of plague in
      Vietnam's Central Highlands is likely resulted from multiple causes that remain
      to be delineated.

PMID- 19584126
TI  - Commentary: Can we facilitate the ethical approval of international observational
      studies?

PMID- 19584127
TI  - Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months.
AB  - Carbon nanotubes (CNT) are of great commercial interest. Theoretically, during
      processing and handling of CNT and in abrasion processes on composites containing
      CNT, inhalable CNT particles might be set free. For hazard assessment, we
      performed a 90-day inhalation toxicity study with a multiwall CNT (MWCNT)
      material (Nanocyl NC 7000) according to Organisation for Economic Co-operation
      and Development test guideline 413. Wistar rats were head-nose exposed for 6
      h/day, 5 days/week, 13 weeks, total 65 exposures, to MWCNT concentrations of 0
      (control), 0.1, 0.5, or 2.5 mg/m(3). Highly respirable dust aerosols were
      produced with a proprietary brush generator which neither damaged the tube
      structure nor increased reactive oxygen species on the surface. Inhalation
      exposure to MWCNT produced no systemic toxicity. However, increased lung weights,
      pronounced multifocal granulomatous inflammation, diffuse histiocytic and
      neutrophilic inflammation, and intra-alveolar lipoproteinosis were observed in
      lung and lung-associated lymph nodes at 0.5 and 2.5 mg/m(3). These effects were
      accompanied by slight blood neutrophilia at 2.5 mg/m(3). Incidence and severity
      of the effects were concentration related. At 0.1 mg/m(3), there was still
      minimal granulomatous inflammation in the lung and in lung-associated lymph
      nodes; a no observed effect concentration was therefore not established in this
      study. The test substance has low dust-forming potential, as demonstrated by
      dustiness measurements, but nonetheless strict industrial hygiene measures must
      be taken during handling and processing. Toxicity and dustiness data such as
      these can be used to compare different MWCNT materials and to select the material
      with the lowest risk potential for a given application.

PMID- 19584128
TI  - Floral thermogenesis of three species of Hydnora (Hydnoraceae) in Africa.
AB  - BACKGROUND AND AIMS: Floral thermogenesis occurs in at least 12 families of
      ancient seed plants. Some species show very high rates of respiration through the
      alternative pathway, and some are thermoregulatory, with increasing respiration
      at decreasing ambient temperature. This study assesses the intensity and
      regulation of respiration in three species of African Hydnora that represent the
      Hydnoraceae, an unusual family of holoparasitic plants from arid environments.
      METHODS: Long-term respirometry (CO(2) production) and thermometry were carried
      out on intact flowers of H. africana, H. abyssinica and H. esculenta in the
      field, and short-term measurements were made on floral parts during the
      protogynous flowering sequence. KEY RESULTS: For H. africana, there was no
      temperature elevation in either the osmophores or the gynoecial chamber in any
      phase, and mass-specific respiration rates of the flower parts were low (maximum
      8.3 nmol CO(2) g(-1) s(-1) in osmophore tissue). Respiration tracked ambient and
      floral temperatures, eliminating the possibility of the inverse relationship
      expected in thermoregulatory flowers. Hydnora abyssinica flowers had higher
      respiration (maximum 27.5 nmol g(-1) s(-1) in the osmophores) and a slight
      elevation of osmophore temperature (maximum 2.8 degrees C) in the female stage.
      Respiration by gynoecial tissue was similar to that of osmophores in both
      species, but there was no measurable elevation of gynoecial chamber temperature.
      Gynoecial chamber temperature of H. esculenta could reach 3.8 degrees C above
      ambient, but there are no respiration data available. Antheral tissue respiration
      was maximal in the male phase (4.8 nmol g(-1) s(-1) in H. africana and 10.3 nmol
      g(-1) s(-1) in H. abyssinica), but it did not raise the antheral ring
      temperature, which showed that thermogenesis is not a by-product of pollen
      maturation or release. CONCLUSIONS: The exceptionally low thermogenesis in
      Hydnora appears to be associated with scent production and possibly gynoecial
      development, but has little direct benefit to beetle pollinators.

PMID- 19584129
TI  - Isotemporal substitution paradigm for physical activity epidemiology and weight
      change.
AB  - For a fixed amount of time engaged in physical activity, activity choice may
      affect body weight differently depending partly on other activities'
      displacement. Typical models used to evaluate effects of physical activity on
      body weight do not directly address these substitutions. An isotemporal
      substitution paradigm was developed as a new analytic model to study the time
      substitution effects of one activity for another. In 1991-1997, the authors
      longitudinally examined the associations of discretionary physical activities,
      with varying activity displacements, with 6-year weight loss maintenance among
      4,558 healthy, premenopausal US women who had previously lost >5% of their
      weight. Results of isotemporal substitution models indicated widely heterogeneous
      relations with each physical activity type (P < 0.001) depending on the displaced
      activities. Notably, whereas 30 minutes/day of brisk walking substituted for 30
      minutes/day of jogging/running was associated with weight increase (1.57 kg, 95%
      confidence interval: 0.33, 2.82), brisk walking was associated with lower weight
      when substituted for slow walking (-1.14 kg, 95% confidence interval: -1.75, 
      0.53) and with even lower weight when substituted for TV watching. Similar
      heterogeneous relations with weight change were found for each activity type (TV
      watching, slow walking, brisk walking, jogging/running) when displaced by other
      activities across these various models. The isotemporal substitution paradigm may
      offer new insights for future public health recommendations.

PMID- 19584130
TI  - Marital trajectories and mortality among US adults.
AB  - More than a century of empirical evidence links marital status to mortality.
      However, the hazards of dying associated with long-term marital trajectories and
      contributing risk factors are largely unknown. The authors used 1992-2006
      prospective data from a cohort of US adults to investigate the impact of current
      marital status, marriage timing, divorce and widow transitions, and marital
      durations on mortality. Multivariate hazard ratios were significantly higher for
      adults currently divorced and widowed, married at young ages (< or =18 years),
      who accumulated divorce and widow transitions (among women), and who were
      divorced for 1-4 years. Results also showed significantly lower risks of
      mortality for men married after age 25 years compared with on time (ages 19-25
      years) and among women experiencing > or =10 years of divorce and > or =5 years
      of widowhood relative to those without exposure to these statuses. For both
      sexes, accumulation of marriage duration was the most robust predictor of
      survival. Results from risk-adjusted models indicated that socioeconomic
      resources, health behaviors, and health status attenuated the associations in
      different ways for men and women. The study demonstrates that traditional
      measures oversimplify the relation between marital status and mortality and that
      sex differences are related to a nexus of marital experiences and associated
      health risks.

PMID- 19584131
TI  - Invited commentary: toward a more comprehensive social epidemiology of marital
      trajectories and mortality.
AB  - In this issue of the Journal, Dupre et al. (Am J Epidemiol. 2009;170(5):546-555)
      use data from a nationally representative cohort of older US adults to examine
      the association of current marital status, timing of first marriage, number and
      kind of transitions out of marriage, and durations spent in various marital
      statuses with the risk of all-cause mortality. Their study offers a wealth of
      empirical findings that make important contributions to research on the relation
      between marital status and mortality. The richness of their findings suggests the
      need for future research to provide a more complete account of the mechanisms
      that lead from specific dimensions of marital status (and family structure more
      broadly) to mortality or other health outcomes over the life course.

PMID- 19584132
TI  - Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the
      multiethnic cohort study.
AB  - In many epidemiologic studies, investigators have reported an inverse relation
      between nonsteroidal antiinflammatory drugs (NSAIDs) and colon cancer, but fewer
      researchers have examined the relation with gastric cancer. Cases for this study
      consisted of incident gastric adenocarcinomas (n = 643) identified between 1993
      and 2004 among members of the Multiethnic Cohort (Hawaii and Los Angeles,
      California). Aspirin and nonaspirin NSAID use was assessed on the basis of a self
      administered questionnaire. Multivariate-adjusted hazards ratios and 95%
      confidence intervals were calculated using Cox proportional hazards regression.
      Compared with no regular use, regular use of aspirin was associated with a
      decreased risk of distal gastric cancer (hazard ratio (HR) = 0.73, 95% confidence
      interval (CI): 0.61, 0.89; P(trend) = 0.009), but use of nonaspirin NSAIDs was
      not (HR = 1.00, 95% CI: 0.81, 1.24; P(trend) = 0.99). The inverse association
      with regular aspirin use was observed only for intestinal-type distal gastric
      adenocarcinoma (HR = 0.66, 95% CI: 0.47, 0.95; P(trend) = 0.01), as opposed to
      diffuse-type distal gastric adenocarcinoma (HR = 0.92, 95% CI: 0.53, 1.60;
      P(trend) = 0.45). In this study, the authors found aspirin use to be inversely
      associated with distal gastric adenocarcinoma, particularly of the intestinal
      type.

PMID- 19584133
TI  - Suicide among US veterans: A prospective study of 500,000 middle-aged and elderly
      men.
AB  - Expert opinion is divided about whether US military veterans, the vast majority
      of whom are middle-aged or older, are at increased risk of suicide. To assess the
      risk of suicide associated with veteran status, the authors conducted a
      prospective cohort study of 499,356 male participants in the Cancer Prevention
      Study II. Participants reported their veteran status and other characteristics in
      1982 and were followed for mortality through 2004. The relative risk of mortality
      from suicide according to veteran status at baseline was estimated by using Cox
      proportional hazards models. During follow-up, 1,248 veterans and 614 nonveterans
      died by suicide. In age-adjusted analyses, the risk of suicide did not differ by
      veteran status. Additional adjustment for several sociodemographic, behavioral,
      and clinical factors had little effect on hazard ratios. The authors concluded
      that the risk of death from suicide among middle-aged and older US males is
      independent of veteran status and suggest that policies to prevent veteran
      suicide should focus on factors that may heighten suicide risk rather than on
      veteran status per se.

PMID- 19584134
TI  - Increased late sodium currents are related to transcription of neuronal isoforms
      in a pressure-overload model.
AB  - AIMS: The late and persistent sodium current (I(Na)) has been identified as a
      target for anti-arrhythmia drugs in patients with heart failure (HF). However,
      the underlying mechanism of late I(Na) (I(NaL)) production remains uncertain. We
      hypothesized that transcriptional alteration among sodium channel (NaCh) isoforms
      may contribute to I(NaL) in failing cardiomyocytes. METHODS AND RESULTS: Pressure
      overload rat models were created by 16-week constriction of the ascending aorta
      (HF). Haemodynamic and electrocardiographic variables were studied in sham
      operation and HF rats. Action potential (AP) and I(Na) were recorded using whole
      cell patch-clamp techniques. The expression of various NaCh isoforms was
      evaluated by immunocytochemistry, RT-PCR, and western blot. The HF group
      exhibited left ventricular enlargement, systolic dysfunction, and prolongation of
      QTc intervals (P < 0.05). Current-clamp recording indicated that AP durations
      (APDs) were more sensitive to tetrodotoxin. Voltage-clamp recordings showed that
      I(NaL) was increased (-1.54 +/- 0.43 vs. -1.08 +/- 0.38 pA/pF, P < 0.01) in HF,
      but transient I(Na) (I(NaT)) density was decreased (-14.61 +/- 2.30 vs. -26.15 +/
      5.17 pA/pF, P < 0.01). Correspondingly, the relative mRNA levels of the neuronal
      isoforms SCN1a and SCN8a increased 2.5- and 2.7-fold, respectively; SCN3a did not
      change, whereas SCN5a decreased by approximately 60% in HF. Protein levels
      paralleled their mRNA expression. CONCLUSION: The up-regulated expression of the
      neuronal NaCh isoforms SCN1a and SCN8a could be one mechanism of I(NaL)
      production, which may contribute to prolongation of APD in the failing heart.

PMID- 19584135
TI  - Characterization of CD30 expression in human embryonic stem cell lines cultured
      in serum-free media and passaged mechanically.
AB  - BACKGROUND: The presence of chromosomal abnormalities could have a negative
      impact for human embryonic stem cell (hESC) applications both in regenerative
      medicine and in research. A biomarker that allows the identification of
      chromosomal abnormalities induced in hESC in culture before they take over the
      culture would represent an important tool for defining optimal culture conditions
      for hESC. Here we investigate the expression of CD30, reported to be a biomarker
      of hESCs with abnormal karyotype, in undifferentiated and spontaneously
      differentiated hESC. METHODS AND RESULTS: hESC were derived and cultured on mouse
      fibroblasts in KO-SR containing medium (serum free media) and passaged
      mechanically. Our results based on analysis at mRNA (RT-PCR) and protein
      (fluorescence-activated cell sorting and immunocytochemistry) level show that
      CD30 is expressed in undifferentiated hESC, even at very early passages, without
      any correlation with the presence of chromosomal anomalies. We also show that the
      expression of CD30 is rapidly lost during early spontaneous differentiation of
      hESC. CONCLUSION: We conclude that CD30 expression in hESC cultures is probably a
      consequence of culture conditions, and that KO-SR may play a role. In addition,
      the expression of so-called 'stemness' markers does not change in
      undifferentiated hESC during long-term culture or when cells acquire chromosomal
      abnormalities.

PMID- 19584136
TI  - Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in
      spermatozoa from infertile men.
AB  - BACKGROUND: In mammals, oocyte activation at fertilization is thought to be
      induced by the sperm-specific phospholipase C zeta (PLCzeta). However, it still
      remains to be conclusively shown that PLCzeta is the endogenous agent of oocyte
      activation. Some types of human infertility appear to be caused by failure of the
      sperm to activate and this may be due to specific defects in PLCzeta. METHODS AND
      RESULTS: Immunofluorescence studies showed PLCzeta to be localized in the
      equatorial region of sperm from fertile men, but sperm deficient in oocyte
      activation exhibited no specific signal in this same region. Immunoblot analysis
      revealed reduced amounts of PLCzeta in sperm from infertile men, and in some
      cases, the presence of an abnormally low molecular weight form of PLCzeta. In one
      non-globozoospermic case, DNA analysis identified a point mutation in the PLCzeta
      gene that leads to a significant amino acid change in the catalytic region of the
      protein. Structural modelling suggested that this defect may have important
      effects upon the structure and function of the PLCzeta protein. cRNA
      corresponding to mutant PLCzeta failed to induce calcium oscillations when
      microinjected into mouse oocytes. Injection of infertile human sperm into mouse
      oocytes failed to activate the oocyte or trigger calcium oscillations. Injection
      of such infertile sperm followed by two calcium pulses, induced by assisted
      oocyte activation, activated the oocytes without inducing the typical pattern of
      calcium oscillations. CONCLUSIONS: Our findings illustrate the importance of
      PLCzeta during fertilization and suggest that mutant forms of PLCzeta may
      underlie certain types of human male infertility.

PMID- 19584137
TI  - Medicine and public health in a multiethnic world.
AB  - Achievement of medical and public health goals requires mutual understanding
      between professionals and the public, a challenge in diverse societies. Despite
      their massive diversity humans belong to one species, with race and ethnicity
      used to subgroup/classify humans and manage diversity. Classifications are
      contextual and vary by time, place and classifier. As classifications show major
      variations in health status, and risk factors, research using race and ethnicity
      has accelerated. Medical sciences, including epidemiology, are learning fast to
      extract value from such data. Among the debatable issues is the value of the
      relative risk versus absolute risk approaches (the latter is gaining ground), and
      how to assess ethnicity and race (self-assignment is favoured in the UK and North
      America, country of birth in continental Europe). Racial and ethnic variations in
      disease and risk factors are often large and usually unexplained. There is a
      compelling case for ethnic monitoring, despite its difficulties, for tackling
      inequalities and as a foundation for research. Medical and public health goals
      require good data collected in a racism-free social environment. Health
      professionals need to find the benefits of exploring differences while avoiding
      social division. Advances in health care, public health and medical science will
      follow.

PMID- 19584138
TI  - Deficient deletion of apoptotic cells by macrophage migration inhibitory factor
      (MIF) overexpression accelerates photocarcinogenesis.
AB  - Chronic ultraviolet (UV) exposure can increase the occurrence of p53 mutations,
      thus leading to a dysregulation of apoptosis and the initiation of skin cancer.
      Therefore, it is extremely important that apoptosis is induced quickly after UV
      irradiation, without any dysregulation. Recent studies have suggested a
      potentially broader role for macrophage migration inhibitory factor (MIF) in
      growth regulation via its ability to antagonize p53-mediated gene activation and
      apoptosis. To further elucidate the possible role of MIF in photocarcinogenesis,
      the acute and chronic UVB effect in the skin was examined using macrophage
      migration inhibitory factor transgenic (MIF Tg) and wild-type (WT) mice. The MIF
      Tg mice exposed to chronic UVB irradiation began to develop skin tumors after
      approximately 14 weeks, whereas the WT mice began to develop tumors after 18
      weeks. A higher incidence of tumors was observed in the MIF Tg in comparison with
      the WT mice after chronic UVB irradiation. Next, we clarified whether the
      acceleration of photo-induced carcinogenesis in the MIF Tg mice was mediated by
      the inhibition of apoptosis There were fewer sunburned cells in the epidermis of
      the MIF Tg mice than the WT mice after acute UVB exposure. The epidermis derived
      from the MIF Tg mice exhibited substantially decreased levels of p53, bax and p21
      after UVB exposure in comparison with the WT mice. Collectively, these findings
      suggest that chronic UVB exposure enhances MIF production, which may inhibit the
      p53-dependent apoptotic processes and thereby induce photocarcinogenesis in the
      skin.

PMID- 19584140
TI  - Withholding medical records without explanation: a Foucauldian reading of public
      interest.

PMID- 19584141
TI  - Measurement and analysis of radiofrequency radiations from some mobile phone base
      stations in Ghana.
AB  - A survey of the radiofrequency electromagnetic radiation at public access points
      in the vicinity of 50 cellular phone base stations has been carried out. The
      primary objective was to measure and analyse the electromagnetic field strength
      levels emitted by antennae installed and operated by the Ghana Telecommunications
      Company. On all the sites measurements were made using a hand-held spectrum
      analyser to determine the electric field level with the 900 and 1800 MHz
      frequency bands. The results indicated that power densities at public access
      points varied from as low as 0.01 microW m(-2) to as high as 10 microW m(-2) for
      the frequency of 900 MHz. At a transmission frequency of 1800 MHz, the variation
      of power densities is from 0.01 to 100 microW m(-2). The results were found to be
      in compliant with the International Commission on Non-ionizing Radiological
      Protection guidance level but were 20 times higher than the results generally
      obtained for such a practice elsewhere. There is therefore a need to re-assess
      the situation to ensure reduction in the present level as an increase in mobile
      phone usage is envisaged within the next few years.

PMID- 19584139
TI  - Association between global DNA hypomethylation in leukocytes and risk of breast
      cancer.
AB  - BACKGROUND: Global DNA hypomethylation may result in chromosomal instability and
      oncogene activation, and as a surrogate of systemic methylation activity, may be
      associated with breast cancer risk. METHODS: Samples and data were obtained from
      women with incident early-stage breast cancer (I-IIIa) and women who were cancer
      free, frequency matched on age and race. In preliminary analyses, genomic
      methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5
      mdC), as well as methylation analysis of the LINE-1-repetitive DNA element.
      Further analyses used only 5-mdC levels. Logistic regression models were used to
      estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast
      cancer in relation to amounts of methylation. RESULTS: In a subset of samples
      tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC
      level in leukocyte DNA was significantly lower in breast cancer cases than
      healthy controls (P = 0.001), but no significant case-control differences were
      observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted
      significant differences in 5-mdC levels in leukocytes between cases (n = 176) and
      controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC
      tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84-2.65) and lowest
      tertile (T1; OR = 2.86, 95% CI = 1.65-4.94) had higher risk of breast cancer (P
      for trend < or = 0.001). Among controls only and cases and controls combined,
      only alcohol intake was found to be inversely associated with methylation levels.
      CONCLUSION: These findings suggest that leukocyte DNA hypomethylation is
      independently associated with development of breast cancer.

PMID- 19584142
TI  - Phylogenomic analysis demonstrates a pattern of rare and ancient horizontal gene
      transfer between plants and fungi.
AB  - Horizontal gene transfer (HGT) describes the transmission of genetic material
      across species boundaries and is an important evolutionary phenomenon in the
      ancestry of many microbes. The role of HGT in plant evolutionary history is,
      however, largely unexplored. Here, we compare the genomes of six plant species
      with those of 159 prokaryotic and eukaryotic species and identify 1689 genes that
      show the highest similarity to corresponding genes from fungi. We constructed a
      phylogeny for all 1689 genes identified and all homolog groups available from the
      rice (Oryza sativa) genome (3177 gene families) and used these to define 14
      candidate plant-fungi HGT events. Comprehensive phylogenetic analyses of these 14
      data sets, using methods that account for site rate heterogeneity, demonstrated
      support for nine HGT events, demonstrating an infrequent pattern of HGT between
      plants and fungi. Five HGTs were fungi-to-plant transfers and four were plant-to
      fungi HGTs. None of the fungal-to-plant HGTs involved angiosperm recipients.
      These results alter the current view of organismal barriers to HGT, suggesting
      that phagotrophy, the consumption of a whole cell by another, is not necessarily
      a prerequisite for HGT between eukaryotes. Putative functional annotation of the
      HGT candidate genes suggests that two fungi-to-plant transfers have added
      phenotypes important for life in a soil environment. Our study suggests that
      genetic exchange between plants and fungi is exceedingly rare, particularly among
      the angiosperms, but has occurred during their evolutionary history and added
      important metabolic traits to plant lineages.

PMID- 19584145
TI  - Revealing tumor immunity after hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation is currently the most
      effective method for inducing tumor immunity. However, the diversity of target
      antigens recognized by donor T cells has not been established. New studies show
      that tumor-reactive T cells are directed against diverse tumor-specific targets
      as well as minor histocompatibility antigens.

PMID- 19584143
TI  - Shoot Na+ exclusion and increased salinity tolerance engineered by cell type
      specific alteration of Na+ transport in Arabidopsis.
AB  - Soil salinity affects large areas of cultivated land, causing significant
      reductions in crop yield globally. The Na+ toxicity of many crop plants is
      correlated with overaccumulation of Na+ in the shoot. We have previously
      suggested that the engineering of Na+ exclusion from the shoot could be achieved
      through an alteration of plasma membrane Na+ transport processes in the root, if
      these alterations were cell type specific. Here, it is shown that expression of
      the Na+ transporter HKT1;1 in the mature root stele of Arabidopsis thaliana
      decreases Na+ accumulation in the shoot by 37 to 64%. The expression of HKT1;1
      specifically in the mature root stele is achieved using an enhancer trap
      expression system for specific and strong overexpression. The effect in the shoot
      is caused by the increased influx, mediated by HKT1;1, of Na+ into stelar root
      cells, which is demonstrated in planta and leads to a reduction of root-to-shoot
      transfer of Na+. Plants with reduced shoot Na+ also have increased salinity
      tolerance. By contrast, plants constitutively expressing HKT1;1 driven by the
      cauliflower mosaic virus 35S promoter accumulated high shoot Na+ and grew poorly.
      Our results demonstrate that the modification of a specific Na+ transport process
      in specific cell types can reduce shoot Na+ accumulation, an important component
      of salinity tolerance of many higher plants.

PMID- 19584146
TI  - Inhibition of PI3K and MEK: it is all about combinations and biomarkers.
AB  - A small molecule inhibitor of MAP/ERK kinase (MEK) was effective against human
      breast cancer cells with a basal-like gene expression signature. Antitumor
      activity was limited by both feedback upregulation of phosphatidylinositol-3
      kinase (PI3K)/AKT upon inhibition of MEK as well as loss of the phosphatase PTEN.
      Therefore, MEK inhibitors should preferably be investigated in combination with
      PI3K inhibitors in basal-like breast cancers.

PMID- 19584148
TI  - Partially matched related donor transplantation can achieve outcomes comparable
      with unrelated donor transplantation for patients with hematologic malignancies.
AB  - PURPOSE: The study aimed to compare the outcomes of patients undergoing
      hematopoietic stem cell transplantation (HSCT) from partially matched related
      donors (PMRD) and unrelated donors (URD) for hematologic malignancies without the
      use of in vitro T cell depletion. EXPERIMENTAL DESIGN: HSCT was done on 297
      consecutive patients from URDs (n = 78) and PMRDs (n = 219) during the same time
      period. Incidences of graft-versus-host disease (GVHD), relapse, nonrelapse
      mortality, overall survival, and leukemia-free survival between the PMRD and URD
      groups were compared. RESULTS: All patients achieved full engraftment. The
      cumct65ulative incidences of grades II to IV acute GVHD in the PMRD and URD
      cohorts were 47% [95% confidence interval (95% CI), 33-62%] versus 31% (CI, 20
      42%; P = 0.033), with a relative risk of 1.72 (95% CI, 1.01-2.94; P = 0.046). The
      incidence of chronic GVHD did not differ significantly between the two cohorts (P
      = 0.17). The 2-year incidences of nonrelapse mortality and relapse were 20% (CI,
      15-26%) versus 18% (CI, 10-27%), with P = 0.98, and 12% (CI, 8-16%) versus 18%
      (CI, 10-27%), with P = 0.12, for the PMRD versus the URD cohort, respectively.
      The 4-year overall survival and leukemia-free survival were 74% (CI, 67-80%)
      versus 74% (CI, 62-85%), with P = 0.98, and 67% (CI, 59-75%) versus 61% (CI, 47
      74%), with P = 0.74, respectively. CONCLUSIONS: Our comparisons show that every
      major end point, including relapse, nonrelapse mortality, overall survival, and
      leukemia-free survival, was comparable between the PMRD and the URD groups.

PMID- 19584149
TI  - Human leukocyte antigen-G protein expression is an unfavorable prognostic
      predictor of hepatocellular carcinoma following curative resection.
AB  - PURPOSE: Human leukocyte antigen-G (HLA-G) is a tumor-associated
      immunosuppressive molecule involved in tumor escape mechanisms. The aim of this
      study is to elucidate its prognostic significance in hepatocellular carcinoma
      (HCC). EXPERIMENTAL DESIGN: Immunohistochemical staining of HLA-G expression as
      well as tumor-infiltrating FoxP3+ regulatory (Tregs) and CD8+ cytotoxic T cells
      was carried out on tissue microarrays containing 173 HCC tissue specimens.
      Membrane-bound HLA-G1 protein expression in five human HCC cell lines was
      detected by Western blot. RESULTS: HLA-G expression was associated with HCC
      prognosis, especially in early-stage diseases, with high expression independently
      associated with shortened overall survival (P = 0.041) and increased tumor
      recurrence (P = 0.023). HLA-G level was positively related to Tregs/CD8+ ratio
      and their combination served as a better prognosticator, patients having
      concurrent high levels of both variables at more than three times of risk of
      death and tumor relapse than those with concurrent low levels (both P < 0.001).
      In addition, HLA-G1 expression increased in a concordant manner with the increase
      of metastatic potential in human HCC cell lines. CONCLUSIONS: Overexpression of
      HLA-G protein in HCC was an independent indicator for poor outcome especially in
      early-stage disease. The combination of HLA-G expression and Tregs/CD8+ ratio
      added the prognostic power to both variables, offering a possible strategy of
      tumor-stroma interaction-oriented cancer immunotherapy.

PMID- 19584147
TI  - Prevention of radiation-induced oral mucositis after adenoviral vector-mediated
      transfer of the keratinocyte growth factor cDNA to mouse submandibular glands.
AB  - PURPOSE: The study aims to evaluate if human keratinocyte growth factor (hKGF),
      secreted after transduction of murine salivary glands with adenoviral vectors,
      can prevent oral mucositis resulting from radiation. EXPERIMENTAL DESIGN: Two
      serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1alpha-hKGF and
      AdLTR(2)EF1alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single
      (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis
      (ulcers on tongue). One day before irradiation, the above viral vectors or an
      empty vector, Adcontrol, was given (10(10) particles per gland) to both
      submandibular glands by retrograde ductal instillation. Each experiment included
      five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1alpha-hKGF, or
      AdLTR(2)EF1alpha-hKGF). Blood, saliva, submandibular glands, and tongue were
      collected on day 7 for single-dose studies or day 10 for fractionated dosing.
      hKGF levels were measured by ELISA. RESULTS: In three separate single-dose
      irradiation experiments, lingual ulcers were dramatically reduced after either
      KGF-expressing vector. Similarly, in two separate fractionated irradiation
      experiments, the hKGF-expressing vectors completely prevented ulcer formation.
      QPCR data indicated that approximately 10(7) to 10(8) particles of each vector
      remained in the targeted submandibular glands at the terminal time. Transgenic
      hKGF protein was found at high levels in saliva, serum, and submandibular gland
      extracts. CONCLUSIONS: hKGF gene transfer to salivary glands prevented radiation
      induced oral mucositis in mice. This proof of concept study suggests that
      transgenic hKGF secreted from transduced salivary glands may be useful clinically
      to prevent oral mucositis caused by radiation.

PMID- 19584151
TI  - SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer.
AB  - PURPOSE: Recently, the majority of protein coding genes were sequenced in a
      collection of pancreatic cancers, providing an unprecedented opportunity to
      identify genetic markers of prognosis for patients with adenocarcinoma of the
      pancreas. EXPERIMENTAL DESIGN: We previously sequenced more than 750 million base
      pairs of DNA from 23,219 transcripts in a series of 24 adenocarcinomas of the
      pancreas. In addition, 39 genes that were mutated in more than one of these 24
      cancers were sequenced in a separate panel of 90 well-characterized
      adenocarcinomas of the pancreas. Of these 114 patients, 89 underwent
      pancreaticoduodenectomy, and the somatic mutations in these cancers were
      correlated with patient outcome. RESULTS: When adjusted for age, lymph node
      status, margin status, and tumor size, SMAD4 gene inactivation was significantly
      associated with shorter overall survival (hazard ratio, 1.92; 95% confidence
      interval, 1.20-3.05; P = 0.006). Patients with SMAD4 gene inactivation survived a
      median of 11.5 months, compared with 14.2 months for patients without SMAD4
      inactivation. By contrast, mutations in CDKN2A or TP53 or the presence of
      multiple (> or =4) mutations or homozygous deletions among the 39 most frequently
      mutated genes were not associated with survival. CONCLUSIONS: SMAD4 gene
      inactivation is associated with poorer prognosis in patients with surgically
      resected adenocarcinoma of the pancreas.

PMID- 19584152
TI  - Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) promotes angiogenesis and
      vascular permeability. The VEGF gene is polymorphic. We investigated the
      prognostic significance of three VEGF single nucleotide polymorphisms (SNP) in
      esophageal cancer. EXPERIMENTAL DESIGN: Three hundred sixty-one patients were
      genotyped for three VEGF SNPs (-460T/C, 405G/C, and 936C/T) using DNA extracted
      from prospectively collected blood samples. The association of each individual
      SNP, and haplotypes of the three SNPs, on overall survival (OS) was investigated.
      RESULTS: The variant allele of 936C/T was associated with improved OS compared
      with the wild-type genotype (log-rank P < 0.001). This association remained
      significant for OS after adjustments for age, gender, performance status, and
      disease stage [VEGF 936C/T: adjusted hazard ratio (AHR), 0.70; 95% confidence
      interval (95% CI), 0.49-0.99; P = 0.04; VEGF 936T/T: AHR, 0.11; 95% CI, 0.02
      0.82; P = 0.03]. No independent associations were found for VEGF -460T/C and VEGF
      405G/C. The CGC haplotype of the three VEGF SNPs (-460T/C, 405G/C, and 936C/T)
      combined was associated with reduced OS compared with all other patients
      (CGC/CGC: AHR, 1.51; 95% CI, 1.00-2.30; P = 0.05). CONCLUSIONS: VEGF 936C/T, and
      a haplotype of 460T/C, 405G/C, and 936C/T combined, has potential prognostic
      significance in esophageal cancer.

PMID- 19584150
TI  - Relationship of CDX2 loss with molecular features and prognosis in colorectal
      cancer.
AB  - PURPOSE: The homeodomain transcription factor CDX2 is a relatively specific
      immunohistochemical marker for gastrointestinal carcinoma. However, no study has
      comprehensively examined the relationship between CDX2 expression in colon cancer
      and clinical, pathologic, prognostic, and molecular features, including
      microsatellite instability and CpG island methylator phenotype (CIMP).
      EXPERIMENTAL DESIGN: Utilizing 621 colorectal cancers with clinical outcome and
      molecular data, CDX2 loss was detected in 183 (29%) tumors by
      immunohistochemistry. RESULTS: In multivariate logistic regression analysis, CDX2
      loss was associated with female gender [odds ratio (OR), 3.32; P < 0.0001], CIMP
      high (OR, 4.42; P = 0.0003), high tumor grade (OR, 2.69; P = 0.0085), stage IV
      disease (OR, 2.03; P = 0.019), and inversely with LINE-1 hypomethylation (for a
      30% decline; OR, 0.33; P = 0.0031), p53 expression (OR, 0.55; P = 0.011), and
      beta-catenin activation (OR, 0.60; P = 0.037), but not with body mass index,
      tumor location, microsatellite instability, BRAF, KRAS, PIK3CA, p21, or
      cyclooxygenase-2. CDX2 loss was not independently associated with patient
      survival. However, the prognostic effect of CDX2 loss seemed to differ according
      to family history of colorectal cancer (P(interaction) = 0.0094). CDX2 loss was
      associated with high overall mortality (multivariate hazard ratio, 2.40; 95% CI,
      1.28-4.51) among patients with a family history of colorectal cancer; no such
      association was present (multivariate hazard ratio, 0.97; 95% CI, 0.66-1.41)
      among patients without a family history of colorectal cancer. CONCLUSIONS: CDX2
      loss in colorectal cancer is independently associated with female gender, CIMP
      high, high-level LINE-1 methylation, high tumor grade, and advanced stage. CDX2
      loss may be associated with poor prognosis among patients with a family history
      of colorectal cancer.

PMID- 19584153
TI  - Clinical relevance of a pharmacogenetic approach using multiple candidate genes
      to predict response and resistance to imatinib therapy in chronic myeloid
      leukemia.
AB  - PURPOSE: Imatinib resistance is major cause of imatinib mesylate (IM) treatment
      failure in chronic myeloid leukemia (CML) patients. Several cellular and genetic
      mechanisms of imatinib resistance have been proposed, including amplification and
      overexpression of the BCR/ABL gene, the tyrosine kinase domain point mutations,
      and MDR1 gene overexpression. EXPERIMENTAL DESIGN: We investigated the impact of
      16 single nucleotide polymorphisms (SNP) in five genes potentially associated
      with pharmacogenetics of IM, namely ABCB1, multidrug resistance 1; ABCG2, breast
      cancer resistance protein; CYP3A5, cytochrome P450-3A5; SLC22A1, human organic
      cation transporter 1; and AGP, alpha1-acid glycoprotein. The DNAs from peripheral
      blood samples in 229 patients were genotyped. RESULTS: The GG genotype in ABCG2
      (rs2231137), AA genotype in CYP3A5 (rs776746), and advanced stage were
      significantly associated with poor response to IM especially for major or
      complete cytogenetic response, whereas the GG genotype at SLC22A1 (rs683369) and
      advanced stage correlated with high rate of loss of response or treatment failure
      to IM therapy. CONCLUSIONS: We showed that the treatment outcomes of imatinib
      therapy could be predicted using a novel, multiple candidate gene approach based
      on the pharmacogenetics of IM.

PMID- 19584155
TI  - EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding
      locoregional lymph node metastases.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) and its downstream factors
      KRAS and BRAF are mutated with different frequencies in non-small cell lung
      cancer and mutations predict clinical response to EGFR inhibitors. The present
      study compared the mutational status of EGFR, KRAS, and BRAF in primary tumors
      with the one in corresponding lymph node metastases. EXPERIMENTAL DESIGN: Direct
      bidirectional sequencing of EGFR gene exons 18 to 21, KRAS gene codons 12/13 and
      61 to 68, and BRAF exon 15 was done on 96 paired samples of primary lung
      adenocarcinomas and corresponding locoregional lymph node metastases. In
      addition, comparative genomic hybridization analyses in two pairs of
      corresponding primary and metastatic tumor samples with discordant EGFR mutation
      status were done. RESULTS: Mutations in EGFR, KRAS, and BRAF were observed in 7
      (7%), 36 (38%), and 2 (2%) patients, respectively. Interestingly, KRAS mutations
      were observed in two patients with an EGFR mutation. Mutations in primary tumors
      and lymph node metastases were identical in 1 of 7 (14%) patients in case of EGFR
      and 11 of 36 (31%) patients in case of KRAS. One patient harbored different KRAS
      mutations in primary and corresponding metastatic tumors. Comparative genomic
      hybridization analysis revealed similar patterns of chromosomal changes, strongly
      supporting a common clonal origin of primary tumors and metastases. CONCLUSIONS:
      The possibility of differences in the mutational status of EGFR, KRAS, BRAF
      between primary tumors and corresponding lymph node metastases should be
      considered whenever these mutations are used for the selection of patients for
      EGFR-directed tyrosine kinase inhibitor therapy.

PMID- 19584154
TI  - Antiangiogenesis targeting tumor microenvironment synergizes glucuronide prodrug
      antitumor activity.
AB  - PURPOSE: This study is aimed at investigating the in vivo antitumor activity of a
      novel cell-impermeable glucuronide prodrug, 9-aminocamptothecin glucuronide
      (9ACG), and elucidating the synergistically antitumor effects of antiangiogenesis
      therapy by targeting the tumor microenvironment. EXPERIMENTAL DESIGN: We analyzed
      the antitumor effects of 9ACG alone or combined with antiangiogenic monoclonal
      antibody DC101 on human tumor xenografts by measuring tumor growth and mouse
      survival in BALB/c nu/nu nude and NOD/SCID mice. The drug delivery, immune
      response, and angiogenesis status in treated tumors were assessed by high
      performance liquid chromatography, immunohistochemistry, and immunofluorescence
      assays. RESULTS: We developed a nontoxic and cell-impermeable glucuronide
      prodrug, 9ACG, which can only be activated by extracellular beta-glucuronidase to
      become severely toxic. 9ACG possesses potent antitumor activity against human
      tumor xenografts in BALB/c nu/nu nude mice but not for tumors implanted in
      NOD/SCID mice deficient in macrophages and neutrophils, suggesting that these
      cells play an important role in activating 9ACG in the tumor microenvironment.
      Most importantly, antiangiogenic monoclonal antibody DC101 potentiated single
      dose 9ACG antitumor activity and prolonged survival of mice bearing resistant
      human colon tumor xenografts by providing strong beta-glucuronidase activity and
      prodrug delivery through enhancing inflammatory cell infiltration and normalizing
      tumor vessels in the tumor microenvironment. We also show that inflammatory cells
      (neutrophils) were highly infiltrated in advanced human colon cancer tissues
      compared with normal counterparts. CONCLUSIONS: Our study provides in vivo
      evidence that 9ACG has potential for prodrug monotherapy or in combination with
      antiangiognesis treatment for tumors with infiltration of macrophage or
      neutrophil inflammatory cells.

PMID- 19584156
TI  - Targeted delivery of tumor antigens to activated dendritic cells via CD11c
      molecules induces potent antitumor immunity in mice.
AB  - PURPOSE: CD11c is an antigen receptor predominantly expressed on dendritic cells
      (DC), to which antigen targeting has been shown to induce robust antigen-specific
      immune responses. To facilitate targeted delivery of tumor antigens to DCs, we
      generated fusion proteins consisting of the extracellular domain of human HER or
      its rat homologue neu, fused to the single-chain fragment variable specific for
      CD11c (scFv(CD11c)-HER2/neu). EXPERIMENTAL DESIGN: Induction of cellular and
      humoral immune responses and antitumoral activity of the fusion proteins admixed
      with DC-activating CpG oligonucleotides (scFv(CD11c)-HER2/neu(CpG)) were tested
      in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB
      neuT mice developing spontaneous neu-driven mammary carcinomas. RESULTS:
      Vaccination of BALB/c mice with scFv(CD11c)-HER2(CpG) protected mice from
      subsequent challenge with HER2-positive, but not HER2-negative, murine breast
      tumor cells, accompanied by induction of strong HER2-specific T-cell and antibody
      responses. In a therapeutic setting, injection of scFv(CD11c)-HER2(CpG) caused
      rejection of established HER2-positive tumors. Importantly, antitumoral activity
      of such a fusion protein vaccine could be reproduced in immunotolerant BALB-neuT
      mice, where scFv(CD11c)-neu(CpG) vaccination significantly protected against a
      subsequent challenge with neu-expressing murine breast tumor cells and markedly
      delayed the onset of spontaneous mammary carcinomas. CONCLUSIONS: CD11c-targeted
      protein vaccines for in vivo delivery of tumor antigens to DCs induce potent
      immune responses and antitumoral activities and provide a rationale for further
      development of this approach for cancer immunotherapy.

PMID- 19584157
TI  - Identification of a new panel of serum autoantibodies associated with the
      presence of in situ carcinoma of the breast in younger women.
AB  - PURPOSE: We examined the feasibility of using a panel of autoantibodies to
      multiple tumor-associated proteins as a method for early detection of breast
      cancer and, more particularly, carcinoma in situ (CIS). EXPERIMENTAL DESIGN:
      PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens
      by proteomic approaches. The seroreactivity of a panel of antibodies consisting
      of these three antigens and two previously described autoantigens, HSP60 and
      MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from
      CIS patients, and 93 from healthy controls) with the use of specific ELISAs.
      FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by
      reverse transcription-PCR and immunohistochemistry in early-stage breast tumors.
      RESULTS: Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed
      significantly increased reactivity in primary breast cancer and CIS compared with
      healthy controls. When combined, the five markers significantly discriminated
      primary breast cancer [receiver operating characteristic area under the curve,
      0.73; 95% confidence interval (95% CI), 0.60-0.79] and CIS (receiver operating
      characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy
      individuals. Importantly, the receiver operating characteristic-area under the
      curve value of the autoantibody panel was able to distinguish CIS, including high
      grades, from healthy controls in women under the age of 50 years (receiver
      operating characteristic area under the curve, 0.85; 95% CI, 0.61-0.92). Finally,
      only FKBP52 mRNA and protein levels were found to be increased in CIS and primary
      breast cancer compared with healthy breast tissue. CONCLUSIONS: This autoantibody
      assay against a panel of five antigens allows for an accurate discrimination
      between early-stage breast cancer, especially CIS, and healthy individuals. These
      results could be of interest in detecting early breast cancer as an aid to
      mammography, especially in women under the age of 50 years with aggressive
      cancers.

PMID- 19584158
TI  - Receptor-targeted nanoparticles for in vivo imaging of breast cancer.
AB  - PURPOSE: Cell-surface receptor-targeted magnetic iron oxide nanoparticles provide
      molecular magnetic resonance imaging contrast agents for improving specificity of
      the detection of human cancer. EXPERIMENTAL DESIGN: The present study reports the
      development of a novel targeted iron oxide nanoparticle using a recombinant
      peptide containing the amino-terminal fragment of urokinase-type plasminogen
      activator (uPA) conjugated to magnetic iron oxide nanoparticles amino-terminal
      fragment conjugated-iron oxide (ATF-IO). This nanoparticle targets uPA receptor,
      which is overexpressed in breast cancer tissues. RESULTS: ATF-IO nanoparticles
      are able to specifically bind to and be internalized by uPA receptor-expressing
      tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing s.c. and
      i.p. mammary tumors leads to the accumulation of the particles in tumors,
      generating a strong magnetic resonance imaging contrast detectable by a clinical
      magnetic resonance imaging scanner at a field strength of 3 tesla. Target
      specificity of ATF-IO nanoparticles showed by in vivo magnetic resonance imaging
      is further confirmed by near-IR fluorescence imaging of the mammary tumors using
      near-IR dye-labeled amino-terminal fragment peptides conjugated to iron oxide
      nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower
      uptake of the particles in the liver and spleen compared with those receiving
      nontargeted iron oxide nanoparticles. CONCLUSIONS: Our results suggest that uPA
      receptor-targeted ATF-IO nanoparticles have potential as molecularly targeted,
      dual modality imaging agents for in vivo imaging of breast cancer.

PMID- 19584159
TI  - PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates
      docetaxel-induced efficacy in xenografts.
AB  - PURPOSE: Checkpoint kinase 1 (Chk1) plays a critical role in the activation of
      mitotic spindle checkpoint and DNA damage checkpoint. We examined the preclinical
      use of the Chk1 inhibitor PF-00477736 as a docetaxel-sensitizing agent.
      Specifically, we investigated the correlation between PF-00477736-mediated
      modulation of biomarkers and the sensitization of docetaxel efficacy.
      EXPERIMENTAL DESIGN: In vitro and in vivo studies using COLO205 and other cell
      lines were done to assess PF-00477736-induced enhancement of docetaxel efficacy
      and effects on associated biomarkers. RESULTS: PF-00477736 significantly enhanced
      the docetaxel-induced efficacy in tumor cells and xenografts. Docetaxel induced
      dose- and time-dependent increase in the levels of phosphorylated Chk1
      (Ser(345)), phosphorylated histone H3 (Ser(10)), and gammaH2AX foci and promoted
      the cytoplasmic localization of phosphorylated Cdc25C (Ser(216)). PF-00477736
      cotreatment suppressed docetaxel-induced changes in phosphorylated histone H3 and
      cytoplasmic phosphorylated Cdc25C (Ser(216)) levels and concurrently sensitized
      the docetaxel-induced apoptosis. Docetaxel alone or in combination with PF
      00477736 induced significant antiproliferative activity in xenografts, shown via
      [18F]FLT-PET imaging. However, changes in [18F]FLT uptake did not reflect the
      potentiation of docetaxel efficacy. In contrast, bioluminescence imaging showed
      that PF-00477736 sensitized docetaxel-induced suppression of tumor survival.
      CONCLUSIONS: Docetaxel triggers mitotic spindle checkpoint activation at low
      concentrations and activates both the DNA damage checkpoint and the spindle
      checkpoint at high concentrations. In combination with docetaxel, PF-00477736
      abrogates the mitotic checkpoint, as well as the DNA damage checkpoint, and
      results in sensitization to docetaxel. Chk1 inhibitor PF-00477736 offers a
      therapeutic potential for the enhancement of taxane therapy.

PMID- 19584160
TI  - Regulation of replicative and stress-induced senescence by RSK4, which is down
      regulated in human tumors.
AB  - PURPOSE: The control of senescence and its biochemical pathways is a crucial
      factor for understanding cell transformation. In a large RNA interference screen,
      the RSK4 gene was found to be related to p53-dependent arrest. The purpose of the
      present study was to investigate the potential role of RSK4 as a tumor suppressor
      gene. EXPERIMENTAL DESIGN: RSK4 expression was determined by quantitative real
      time PCR and immunoblot in 30 colon and 20 renal carcinomas, and in 7 colon
      adenomas. Two HCT116 colon carcinoma cell lines (p53 wt and p53 null), IMR90
      human fibroblasts, and E1A-expressing IMR90 cells were infected with RSK4 cDNA
      and/or shRNA. RSK4 expression levels were analyzed in HCT116 p53 wt or p53 null
      and IMR90 after senescence induction by quantitative real-time PCR and Western
      blot. RESULTS: The RSK4 gene was down-regulated in 27 of 30 colon carcinomas (P <
      0.001), 16 of 20 renal cell carcinomas (P < 0.01), and 6 of 7 colon adenomas (P <
      0.01). In vitro overexpression of RSK4 induced cell arrest and senescence
      features in normal fibroblasts and malignant colon carcinoma cell lines.
      Interestingly, in these cell lines RSK4 mRNA levels were increased both in
      replicative and stress-induced senescence. Moreover, IMR90 partially immortalized
      by RSK4 shRNA and HCT116 with this short hairpin RNA were more resistant to
      cisplatin treatment. Finally, cells expressing E1A or Rb short interfering RNA
      were resistant to RSK4-mediated senescence. CONCLUSION: These results support the
      concept that RSK4 may be an important tumor suppressor gene by modulating
      senescence induction and contributing to cell proliferation control in colon
      carcinogenesis and renal cell carcinomas.

PMID- 19584161
TI  - MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate
      temozolomide resistance.
AB  - PURPOSE: Over the past few years, the alkylating agent temozolomide has become
      the standard-of-care therapy for patients with glioblastoma, the most common
      brain tumor. Recently, large-scale cancer genome sequencing efforts have
      identified a hypermutation phenotype and inactivating MSH6 mismatch repair gene
      mutations in recurrent, post-temozolomide glioblastomas, particularly those
      growing more rapidly during temozolomide treatment. This study aimed to clarify
      the timing and role of MSH6 mutations in mediating glioblastoma temozolomide
      resistance. EXPERIMENTAL DESIGN: MSH6 sequence and microsatellite instability
      (MSI) status were determined in matched prechemotherapy and postchemotherapy
      glioblastomas identified by The Cancer Genome Atlas (TCGA) as having
      posttreatment MSH6 mutations. Temozolomide-resistant lines were derived in vitro
      through selective growth under temozolomide, and the MSH6 gene was sequenced in
      resistant clones. The role of MSH6 inactivation in mediating resistance was
      explored using lentiviral short hairpin RNA knockdown and MSH6 reconstitution.
      RESULTS: MSH6 mutations were confirmed in posttreatment TCGA glioblastomas but
      absent in matched pretreatment tumors. The posttreatment hypermutation phenotype
      displayed a signature bias toward CpC transitions and was not associated with
      MSI. In vitro modeling through exposure of an MSH6 wild-type glioblastoma line to
      temozolomide resulted in resistant clones; one clone showed an MSH6 mutation,
      Thr(1219)Ile, that had been independently noted in two treated TCGA
      glioblastomas. Knockdown of MSH6 in the glioblastoma line U251 increased
      resistance to temozolomide cytotoxicity and reconstitution restored cytotoxicity
      in MSH6-null glioma cells. CONCLUSIONS: MSH6 mutations are selected in
      glioblastomas during temozolomide therapy both in vitro and in vivo and are
      causally associated with temozolomide resistance.

PMID- 19584162
TI  - A phase I clinical trial of darinaparsin in patients with refractory solid
      tumors.
AB  - PURPOSE: Darinaparsin, an organic arsenic, targets essential cell survival
      pathways. We determined the dose-limiting toxicity (DLT) and maximum tolerated
      dose of darinaparsin in patients with advanced cancer. EXPERIMENTAL DESIGN:
      Patients with solid malignancies refractory to conventional therapies were
      treated with i.v. darinaparsin daily for 5 days every 4 weeks. The starting dose
      (78 mg/m(2)) escalated to 109, 153, 214, 300, 420, and 588 mg/m(2). A
      conventional "3 + 3" design was used. RESULTS: Forty patients (median age, 61.5
      years; median number of prior therapies, 5) received therapy; 106 cycles were
      given (median, 2; range, 1-12). Twenty patients reported no drug-related
      toxicities. No DLTs were reported at a dose of <420 mg/m(2). At 588 mg/m(2), two
      of four patients developed DLTs, including grade 3 altered mental status and
      ataxia. Of four patients treated at the de-escalated dose of 500 mg/m(2), one
      developed similar toxicities. De-escalating the dose to 420 mg/m(2) (n = 8)
      resulted in two neurologic DLTs. Further de-escalation to 300 mg/m(2) (n = 3)
      resulted in no drug-related toxicities. Arsenic plasma levels peaked on treatment
      day 3, plateaued on day 5, and returned to baseline on day 7. Plasma levels
      varied within cohorts but increased with increasing doses. The median plasma
      arsenic half-life was 16.2 hours. Seven (17.5%) patients had stable disease for >
      or =4 months (median, 6; range, 4-11), including 4 of 17 with colorectal and 2 of
      3 with renal cancer. CONCLUSIONS: The recommended dose for phase II trials is 300
      mg/m(2) i.v. given daily for 5 days every 4 weeks.

PMID- 19584163
TI  - Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate
      biopsy in the United States.
AB  - PURPOSE: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription
      factor is a putatively oncogenic gene rearrangement that is commonly found in
      prostate cancer tissue from men undergoing prostatectomy. However, the prevalence
      of the fusion was less common in samples of transurethral resection of the
      prostate from a Swedish cohort of patients with incidental prostate cancer
      followed by watchful waiting, raising the question as to whether the high
      prevalence in prostatectomy specimens reflects selection bias. We sought to
      determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific
      antigen-screened men undergoing prostate biopsy in the United States.
      EXPERIMENTAL DESIGN: We studied 140 prostate biopsies from the same number of
      patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization
      assay. One hundred and thirty-four samples (100 cancer and 34 benign) were
      assessable. RESULTS: ERG gene rearrangement was detected in 46% of prostate
      biopsies that were found to have prostate cancer and in 0% of benign prostate
      biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform
      growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were
      significantly more frequent in TMPRSS2-ERG fusion-positive prostate cancer
      biopsies than gene fusion-negative prostate cancer biopsies (P < or = 0.04). No
      significant association with Gleason score was detected. In addition, non
      Caucasian patients were less likely to have positive fusion status (P = 0.02).
      CONCLUSIONS: This is the first prospective North American multicenter study to
      characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients
      undergoing needle biopsy irrespective of whether or not they subsequently undergo
      prostatectomy. Our results show that this gene rearrangement is common among
      North American men who have prostate cancer on biopsy, is absent in benign
      prostate biopsy, and is associated with specific morphologic features. These
      findings indicate a need for prospective studies to evaluate the relationship of
      TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate
      cancer in North American men, and a need for the development of noninvasive
      screening tests to detect TMPRSS2-ERG rearrangement.

PMID- 19584164
TI  - Activation of phosphatidylinositol-3'-kinase/AKT signaling is essential in
      hepatoblastoma survival.
AB  - PURPOSE: Hepatoblastoma represents the most frequent malignant liver tumor in
      childhood. The phosphatidylinositol-3'-kinase (PI3K)/AKT pathway is crucial in
      downstream signaling of multiple receptor tyrosine kinases of pathogenic
      importance in hepatoblastoma. Increased PI3K/AKT signaling pathway activity and
      activating mutations of PIK3CA, encoding a PI3K catalytic subunit, have been
      reported in different childhood tumors. The current study was done to analyze the
      role of PI3K/AKT signaling in hepatoblastoma. EXPERIMENTAL DESIGN:
      Immunohistochemical stainings of (Ser473)-phosphorylated (p)-AKT protein, its
      targets p-(Ser9)-GSK-3beta and p-(Ser2448)-mTOR, as well as the cell cycle
      regulators Cyclin D1, p27(KIP1), and p21(CIP1) were done and the PIK3CA gene was
      screened for mutations. In vitro, two hepatoblastoma cell lines treated with the
      PI3K inhibitor LY294002 were analyzed for AKT and GSK-3beta phosphorylation, cell
      proliferation, and apoptosis. Additionally, simultaneous treatments of
      hepatoblastoma with LY294002 and cytotoxic drugs were carried out. RESULTS: Most
      tumors strongly expressed p-AKT, p-GSK-3beta, and p-mTOR; subgroups showed
      significant Cyclin D1, p27(KIP1), and p21(CIP1) expression. One hepatoblastoma
      carried an E545A mutation in the PIK3CA gene. In vitro, PI3K inhibition
      diminished hepatoblastoma cell growth being accompanied by reduced AKT and GSK
      3beta phosphorylation. Flow cytometry and 4', 6-diamidino-2-phenylindole
      stainings showed that PI3K pathway inhibition leads to a substantial increase in
      apoptosis and a decrease in cellular proliferation linked to reduced Cyclin D1
      and increased p27(KIP1) levels. Simultaneous treatment of hepatoblastoma cell
      lines with LY294002 and cytotoxic drugs resulted in positive interactions.
      CONCLUSIONS: Our findings imply that PI3K signaling plays an essential role in
      growth control of hepatoblastoma and might be successfully targeted in multimodal
      therapeutic strategies.

PMID- 19584165
TI  - Combination of viral oncolysis and tumor-specific immunity to control established
      tumors.
AB  - PURPOSE: Advanced-stage cancers are extremely difficult to treat and rarely
      result in a cure. The application of oncolytic viruses is a potential strategy
      for controlling advanced-stage cancer because intratumoral (i.t.) injection of an
      oncolytic virus, such as vaccinia virus, results in tumor cell lysis and
      subsequent release of tumor antigens into the microenvironment. Furthermore, the
      viruses can serve as a vehicle for delivering genes of interest to cancer cells.
      EXPERIMENTAL DESIGN: In the current study, we hypothesize that in tumor-bearing
      mice primed with DNA encoding an immunogenic foreign antigen, ovalbumin (OVA)
      followed by a boost with i.t. administration of vaccinia virus encoding the same
      foreign antigen, OVA, can generate enhanced antitumor effects through the
      combination of viral oncolysis and tumor-specific immunity. RESULTS: We observed
      that tumor-bearing mice primed with OVA DNA and boosted with vaccinia encoding
      OVA (Vac-OVA) generated significant therapeutic antitumor effects as well as
      induced significant levels of OVA-specific CD8+ T cells in two different tumor
      models. Furthermore, treatment with Vac-OVA not only kills the tumor and stromal
      cells directly but also renders the tumor cells and surrounding stromal cells
      susceptible to OVA-specific CD8+ T-cell killing, resulting in enhanced antitumor
      therapeutic effects. CONCLUSIONS: Thus, the current study may provide a novel
      therapeutic strategy for the control of advanced-stage cancers.

PMID- 19584167
TI  - 15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer.
AB  - PURPOSE: We have investigated the expression and regulation of 15
      hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer. EXPERIMENTAL
      DESIGN: Clinical gastric adenocarcinoma samples were analyzed by
      immunohistochemistry and quantitative real-time PCR for protein and mRNA
      expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects
      of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation
      were assessed in gastric cancer cell lines. RESULTS: In a gastric cancer cell
      line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was
      methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine
      restored 15-PGDH expression. In a cell line with a relatively high basal level of
      15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This
      effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH
      promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong
      increase of prostaglandin E(2) production in MKN-28 cells and increased cell
      growth of these cells by 31% in anchorage-independent conditions. In clinical
      gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in
      gastric cancer samples when compared with paired nonneoplastic tissues (n = 26)
      and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210).
      CONCLUSIONS: 15-PGDH is down-regulated in gastric cancer, which could potentially
      lead to accelerated tumor progression. Importantly, our data indicate that a
      proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses
      15-PGDH expression at least partially by inhibiting promoter activity of the 15
      PGDH gene.

PMID- 19584166
TI  - Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical
      models of breast cancer.
AB  - PURPOSE: To evaluate noninvasive imaging methods as predictive biomarkers of
      response to trastuzumab in mouse models of HER2-overexpressing breast cancer. The
      correlation between tumor regression and molecular imaging of apoptosis, glucose
      metabolism, and cellular proliferation was evaluated longitudinally in responding
      and nonresponding tumor-bearing cohorts. EXPERIMENTAL DESIGN: Mammary tumors from
      MMTV/HER2 transgenic female mice were transplanted into syngeneic female mice.
      BT474 human breast carcinoma cell line xenografts were grown in athymic nude
      mice. Tumor cell apoptosis (NIR700-Annexin V accumulation), glucose metabolism [2
      deoxy-2-[18F]fluoro-d-glucose positron emission tomography ([18F]FDG-PET)], and
      proliferation [3'-[18F]fluoro-3'-deoxythymidine-PET ([18F]FLT-PET)] were
      evaluated throughout a biweekly trastuzumab regimen. Imaging metrics were
      validated by direct measurement of tumor size and immunohistochemical analysis of
      cleaved caspase-3, phosphorylated AKT, and Ki67. RESULTS: NIR700-Annexin V
      accumulated significantly in trastuzumab-treated MMTV/HER2 and BT474 tumors that
      ultimately regressed but not in nonresponding or vehicle-treated tumors. Uptake
      of [18F]FDG was not affected by trastuzumab treatment in MMTV/HER2 or BT474
      tumors. [18F]FLT-PET imaging predicted trastuzumab response in BT474 tumors but
      not in MMTV/HER2 tumors, which exhibited modest uptake of [18F]FLT. Close
      agreement was observed between imaging metrics and immunohistochemical analysis.
      CONCLUSIONS: Molecular imaging of apoptosis accurately predicts trastuzumab
      induced regression of HER2+ tumors and may warrant clinical exploration to
      predict early response to neoadjuvant trastuzumab. Trastuzumab does not seem to
      alter glucose metabolism substantially enough to afford [18F]FDG-PET significant
      predictive value in this setting. Although promising in one preclinical model,
      further studies are required to determine the overall value of [18F]FLT-PET as a
      biomarker of response to trastuzumab in HER2+ breast cancer.

PMID- 19584168
TI  - The influence of prostate volume on prostate-specific antigen performance:
      implications for the prostate cancer prevention trial outcomes.
AB  - PURPOSE: Although showing a 25% reduction in the biopsy prevalence of cancer
      compared with placebo in the Prostate Cancer Prevention Trial, finasteride was
      associated with a higher prevalence of high-grade disease. This observation was
      driven by "for-cause" biopsies. We sought to understand how volume-dependent
      changes in prostate-specific antigen test performance characteristics may have
      contributed. EXPERIMENTAL DESIGN: A retrospective review was done on 1,304 men
      referred for initial biopsy with a prostate-specific antigen between 4 and 10
      ng/mL or an abnormal digital rectal examination. Receiver-operator curves and
      positive predictive values were ascertained for prostate-specific antigen
      stratified by diagnosis and prostate volume. RESULTS: The performance of prostate
      specific antigen changed for any and high-grade (Gleason, > or =3 + 4) cancer in
      a volume-specific manner. For any cancer, the area under the curve (AUC)
      decreased from 0.758 to 0.629 to 0.520 as prostate volume increased (<30, 30-50,
      >50 cm(3), respectively). For high-grade cancer, a similar trend was shown (AUC,
      0.712, 0.639, and 0.497, respectively). The positive predictive value of a
      prostate-specific antigen of > or =4 ng/mL was also affected by prostate volume.
      Trends for Gleason < or = 6 decreased as prostate volume increased (positive
      predictive value for <30 cm(3), 25.0%; positive predictive value for 30-50 cm(3),
      23.8%; and positive predictive value for >50 cm(3), 17.3%). A more significant
      trend was seen for high-grade cancer (positive predictive value for <30 cm(3),
      39.0%; positive predictive value for 30-50 cm(3), 22.3%; and positive predictive
      value for >50 cm(3), 10.7%). CONCLUSION: Decreases in prostate volume over time
      and the resultant change in prostate-specific antigen performance characteristics
      may have contributed a bias toward the detection of high-grade disease in the
      finasteride arm of the Prostate Cancer Prevention Trial.

PMID- 19584169
TI  - Color fluorescence ratio for detection of bronchial dysplasia and carcinoma in
      situ.
AB  - BACKGROUND: Autofluorescence bronchoscopy is more sensitive than conventional
      bronchoscopy for detecting early airway mucosal lesions. Decreased specificity
      can lead to excessive biopsy and increased procedural time. Onco-LIFE, a device
      that combines fluorescence and reflectance imaging, allows numeric representation
      by expressing red-to-green ratio (R/G ratio) within the region of interest. The
      aim of the study was to determine if color fluorescence ratio (R/G ratio) added
      to autofluorescence bronchoscopy could provide an objective means to guide
      biopsy. METHODS: Subjects at risk for lung cancer were recruited at two centers:
      VU University Medical Centre (Amsterdam) and BC Cancer Agency (Canada). R/G ratio
      for each site appearing normal or abnormal was measured before biopsy. R/G ratios
      were correlated with pathology, and a receiver operating characteristic curve of
      R/G ratio for high-grade and moderate dysplasia was done. Following analysis of
      the training data set obtained from two centers, a prospective validation study
      was done. RESULTS: Three thousand three hundred sixty-two adequate biopsies from
      738 subjects with their corresponding R/G ratios were analyzed. R/G ratio 0.54
      conferred 85% sensitivity and 80% specificity for the detection of high-grade and
      moderate dysplasia, area under the curve was 0.90, and 95% confidence interval
      was 0.88 to 0.92. In another 70 different sites that were assessed, kappa
      measurements of agreement of R/G ratios with visual scores and pathology were
      0.66 (P < 0.0001) and 0.61 (P < 0.0001), respectively. R/G ratio combined with
      visual score improved specificity to 88% (95% confidence interval, 0.73-0.96) for
      high-grade and moderate dysplasia. CONCLUSION: Color fluorescence ratio can
      objectively guide the bronchoscopist in selecting sites for biopsy with good
      pathologic correlation.

PMID- 19584171
TI  - Neighborhood influences on the academic achievement of extremely low birth weight
      children.
AB  - OBJECTIVE: To examine neighborhood effects on academic achievement of children
      with extremely low birth weight (ELBW <1000 g) and normal birth weight (NBW)
      controls. METHODS: The study included 183 8-year-old children with ELBW born
      during 1992-1995 and 176 sociodemographically similar NBW controls. Academic
      achievement was measured via The Woodcock-Johnson III Academic Skills Cluster.
      RESULTS: Children with ELBW had significantly lower achievement scores (89 +/- 16
      vs. 97 +/- 13). A multilevel estimation of predictors of academic achievement
      revealed that neighborhood poverty was significantly associated with lower
      achievement (beta = -.17; 95% CI -.3, -.05; p < .01). Additional correlates
      included birth weight status, male sex, and parent ratings of attention deficit
      hyperactivity disorder symptoms. Family characteristics included maternal
      education and parent protection. CONCLUSIONS: Neighborhood characteristics affect
      academic achievement of both children with ELBW and NBW controls, over and above
      individual and family influences. Interventions designed to address family and
      neighborhood factors may potentially improve these outcomes.

PMID- 19584172
TI  - Distinct genetic regulation of progression of diabetes and renal disease in the
      Goto-Kakizaki rat.
AB  - Goto-Kakizaki (GK) rats develop early-onset type 2 diabetes (T2D) symptoms, with
      signs of diabetic nephropathy becoming apparent with aging. To determine whether
      T2D and renal disease share similar genetic architecture, we ran a quantitative
      trait locus (QTL) analysis in the F2 progeny of a GK x Brown Norway (BN) rat
      cross. Further, to determine whether genetic components change over time, we ran
      the QTL analysis on phenotypes collected longitudinally, at 3, 6, 9 and 12 mo,
      from the same animals. We confirmed three chromosomal regions that are linked to
      early diabetes phenotypes (chromosomes 1, 5, and 10) and a single region involved
      in the late progression of the disorder (chromosome 4). A single region was
      identified for the onset of the renal phenotype proteinuria (chromosome 5). This
      region overlaps the diabetic QTL, although it is not certain whether similar
      genes are involved in both phenotypes. A second QTL linked to the progression of
      the renal phenotype was found on chromosome 7. Linkage for triglyceride and
      cholesterol levels were also identified (chromosomes 7 and 8, respectively).
      These results demonstrate that, in general, different genetic components control
      diabetic and renal phenotypes in a diabetic nephropathy model. Furthermore, these
      results demonstrate that, over time, different genetic components are involved in
      progression of disease from those that were involved in disease onset. This
      observation would suggest that clinical studies collecting participants over a
      wide age distribution may be diluting genetic effects and reducing power to
      detect true effects.

PMID- 19584170
TI  - Down-regulation of epidermal growth factor receptor by selective expansion of a
      5'-end regulatory dinucleotide repeat in colon cancer with microsatellite
      instability.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) is overexpressed in several
      tumor types, and its expression is influenced by the length of a 5'-end
      microsatellite repeat (CA)n: the longer the repeat, the lower the expression.
      Dinucleotide repeats accumulate insertion/deletion types of mutations in tumors
      with microsatellite instability. We designed this study to estimate the
      occurrence of these mutations in EGFR(CA)n and their relevance in carcinogenesis
      of microsatellite instability-positive colon and gastric tumors. EXPERIMENTAL
      DESIGN: We analyzed the frequency of EGFR(CA)n mutations in vivo in 55 colorectal
      and 14 gastric microsatellite instability-positive cancers, and in vitro in
      single-cell clone cultures of microsatellite instability-positive colon tumor
      cell line LS174. Single-cell clone cultures with different repeat lengths were
      analyzed by fluorescent-activated cell sorter for EGFR cell-surface expression. A
      correlation analysis was done between EGFR(CA)n mutations and mutations in KRAS,
      BRAF, and p53. RESULTS: Unlike single-cell clone cultures, which exhibited higher
      rate of deletions compared with insertions, most of EGFR(CA)n mutations in colon
      and gastric tumors were insertions. Longer EGFR(CA)n correlated with lower EGFR
      cell-surface expression in single-cell clone cultures. In colon cancers, the
      elongation of the repeat was associated negatively with mutations in KRAS and
      BRAF, but not in p53. CONCLUSIONS: The EGFR(CA)n elongation observed in tumors
      cannot be explained by an intrinsic property of this repeat favoring insertions
      versus deletions. Instead, a selection for repeat elongation occurs in
      microsatellite instability-positive tumors, leading to EGFR down-regulation.
      These findings suggest that in microsatellite instability-positive tumors current
      therapies targeting EGFR overexpression may have either no effect or an opposite
      to the expected effect.

PMID- 19584173
TI  - Kininogen gene (KNG) variation has a consistent effect on aldosterone response to
      antihypertensive drug therapy: the GERA study.
AB  - Recent experimental and clinical studies suggested that apart from playing an
      essential role in blood pressure homeostasis, aldosterone is involved in the
      pathophysiology of cardiovascular and renal diseases by inducing structural
      changes in the heart, kidney, and vessel wall. The interindividual variation of
      aldosterone response to antihypertensive treatment is considerable, and is at
      least partially explained by genetic variation. In this study, we investigated
      aldosterone response to two antihypertensive drugs-a thiazide diuretic and an
      angiotensin receptor blocker (ARB). Genetic variations in 50 candidate genes were
      tested for association with aldosterone response in four independent samples:
      African American (AA) responders to a diuretic (n = 289), AA responders to an ARB
      (n = 252), European American (EA) responders to a diuretic (n = 295) and EA
      responders to an ARB (n = 300). Linear regression was used to test the
      association with inclusion of age, sex, and body mass index as covariates. The
      results indicated the existence of one or more variants in the kininogen gene
      (KNG) that influence interindividual variation in aldosterone response. The
      significant association was replicated in three of four studied groups. The
      single nucleotide polymorphism rs4686799 was associated in AA and EA responders
      to the diuretic (P = 0.04 and P = 0.07, respectively), and rs5030062 and rs698078
      were significantly associated in EA responders to the diuretic (P = 0.05 and P =
      0.01) and EA responders to the ARB (P = 0.04 and P = 0.02). Although the clinical
      implication of KNG gene variation to antihypertensive drug response is yet to be
      determined, this novel candidate locus provides important new insights into drug
      response physiology.

PMID- 19584174
TI  - Fusion as the result of sperm-somatic cell interaction.
AB  - The research has been designed to investigate whether acrosome-reacted
      spermatozoa can fuse with somatic cells and to check whether this event may
      involve the molecular machinery implicated in the sperm-egg fusion. Boar
      spermatozoa were capacitated in vitro and then treated with A23187 to induce
      acrosome reaction and activate their fusogenic potential. Reacted spermatozoa,
      loaded with the membrane-permeant fluorescent dye calcein AM, were incubated with
      plated granulosa cells or cells derived from stable cell lines: CRFK, VERO, and
      ESK4. The fusion between spermatozoa and somatic cells was revealed by the
      diffusion of the fluorescent dye from the sperm to the cell as membrane fusion
      and cytoplasmic continuity between the two cells were established. The
      involvement of integrin alpha6 and tetraspanin CD9 in the process of fusion was
      assessed by carrying out the experiment in the presence of antibodies against
      these molecules. Moreover, the incidence of fusion displayed by the different
      cell types used was analyzed in relation to their content in the above molecules
      assessed by western blot and immunostaining. The role of CD9 was additionally
      investigated by using CD9-negative cells. The data presented demonstrate that
      boar spermatozoa can fuse with different somatic cell types derived from
      different species and the process requires the combined presence of both integrin
      and tetraspanin molecules on the cell plasma membrane.

PMID- 19584175
TI  - Neurotrophin NT3 promotes ovarian primordial to primary follicle transition.
AB  - Neurotrophins are growth factors that are known to have a role in promoting cell
      survival and differentiation. The focus of the current study is to examine the
      role of neurotrophins in regulating ovarian primordial follicle development.
      Ovaries from 4-day old rats were placed into organ culture and cultured for 10
      days in the absence or presence of neurotrophin-3 (NT3), brain-derived
      neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries
      with NT3 resulted in a significant (P<0.01) increase in primordial follicle
      development (i.e. primordial to primary follicle transition). Treatment with BDNF
      at high doses of 100-250 ng/ml also significantly (P<0.01) increased primordial
      follicle development, but NGF had no effect. Immunohistochemical studies
      determined that NT3 was present in granulosa cells, interstitial tissue, and in
      the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was
      present in oocytes at all stages of development. Analysis of ovaries that contain
      predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3,
      NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF,
      NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3
      receptor with the tyrphostin AG 879 resulted in oocyte death and a significant
      (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with
      K252a slowed primordial to primary follicle transition. A microarray analysis
      demonstrated that a small number of genes were differentially expressed after NT3
      treatment. Observations indicate that the neurotrophin NT3, acting through the
      NTRK3 receptor in oocytes, promotes the primordial to primary follicle
      transition.

PMID- 19584176
TI  - Decreased circulating lactoferrin in insulin resistance and altered glucose
      tolerance as a possible marker of neutrophil dysfunction in type 2 diabetes.
AB  - CONTEXT: Lactoferrin is an innate immune system protein with multiple beneficial
      health activities. OBJECTIVE: To gain insight in the interaction between innate
      immune system and metabolic disturbances (obesity and insulin resistance), we
      investigated the relationship between circulating lactoferrin and chronic
      inflammation-associated insulin resistance according glucose tolerance status in
      Caucasian population. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES:
      Circulating nonstressed lactoferrin (ELISA), metabolic variables, and
      inflammatory markers were measured in 229 men, 94 with normal (NGT) and 135 with
      altered glucose tolerance (AGT). Lactoferrin secretion by neutrophil was
      investigated in whole-blood culture (four young NGT subjects, four older NGT
      subjects, and four patients with type 2 diabetes) under microbial
      lipopolysaccharide (LPS) with IL-6 and rosiglitazone treatment. We also tested
      the lactoferrin action in THP-1 cells under LPS stimulus. RESULTS: Circulating
      lactoferrin was significantly decreased in patients with AGT (431.5 +/- 187.5 vs.
      493.5 +/- 238.9 ng/ml, P = 0.02). In addition, circulating lactoferrin was
      negatively associated with hyperglycemia and obesity measures and positively with
      insulin sensitivity. Lactoferrin was negatively related to inflammatory markers,
      especially in AGT subjects. In ex vivo experiments, we found a significant
      decrease in LPS-induced lactoferrin release from neutrophils in subjects with
      type 2 diabetes. IL-6 coincubation decreased LPS-induced lactoferrin release in
      NGT subjects (P < 0.001). Finally, rosiglitazone treatment led to increased
      lactoferrin secretion (398 +/- 193 vs. 280.1 +/- 104.9 ng/ml, P < 0.0001).
      Lactoferrin decreased nuclear factor-kappabeta activation and IL-6, IL-8, and
      macrophage chemoattractant protein-1 expression under LPS challenge. CONCLUSIONS:
      Decreased circulating lactoferrin levels may play a role in chronic low level
      inflammation-associated insulin resistance.

PMID- 19584177
TI  - The effects of serum testosterone, estradiol, and sex hormone binding globulin
      levels on fracture risk in older men.
AB  - CONTEXT: The relationship between sex steroids and fracture is poorly understood.
      OBJECTIVE: The objective of the study was to examine associations between
      nonvertebral fracture risk and bioavailable estradiol (bioE2), bioavailable
      testosterone (bioT), and SHBG. DESIGN: This was a case-cohort study. SETTING: The
      Osteoporotic Fractures in Men Study (MrOS) was conducted in a prospective U.S.
      cohort in 5995 community-dwelling men 65 yr old or older. PARTICIPANTS:
      Participants included a subcohort of 1436 randomly chosen white men plus all 446
      minorities and all those with incident hip and other nonvertebral fractures. MAIN
      OUTCOME MEASURES: Baseline testosterone and estradiol were measured by mass
      spectrometry (MS) and SHBG by RIA. RESULTS: Men with the lowest bioE2 (<11.4
      pg/ml) or highest SHBG (>59.1 nm) had greater risk of all nonvertebral fractures
      [adjusted hazard ratio (HR) [95% confidence interval]: 1.5 (1.2-1.9) and 1.4 (1.1
      21.8), respectively]. Men with the lowest bioT (<163.5 ng/dl) had no increased
      fracture risk after adjustment for bioE2 [adjusted HR 1.16 (0.90-1.49)]. A
      significant interaction between SHBG and bioT (P = 0.03) resulted in men with low
      bioT and high SHBG having higher fracture risk [HR 2.1 (1.4-3.2)]. Men with low
      bioE2, low bioT, and high SHBG were at highest risk [HR 3.4 (2.2-5.3)].
      CONCLUSIONS: Older men with low bioE2 or high SHBG levels are at increased risk
      of nonvertebral fracture. When SHBG levels are high, men with low bioT levels
      have higher risk. The strongest association occurred when all measures were
      considered in combination.

PMID- 19584178
TI  - Evidence for a specific defect in hippocampal memory in overt and subclinical
      hypothyroidism.
AB  - CONTEXT: Declarative memory largely depends upon normal functioning temporal
      lobes (hippocampal complex) and prefrontal cortex. Animal studies suggest
      abnormal hippocampal function in hypothyroidism. OBJECTIVE: The aim of the study
      was to assess declarative memory in overt and subclinical (SCH) hypothyroid
      patients before and after l-T(4) (LT4) replacement and in matched normal
      subjects. DESIGN AND SETTING: A prospective, open-labeled interventional study
      was conducted at a teaching hospital. PARTICIPANTS AND INTERVENTION: Hypothyroid
      (n = 21) and SCH (n = 17) patients underwent neuropsychological tests at baseline
      and 3 and 6 months after LT4 replacement. Normal subjects were studied at the
      same time-points. MAIN OUTCOME: Tests of spatial, verbal, associative, and
      working memory; attention; and response inhibition and the Hospital Anxiety and
      Depression Scale were administered. RESULTS: Baseline deficits in spatial,
      associative, and verbal memory, which rely upon the integrity of the hippocampal
      and frontal areas, were identified in patients with overt hypothyroidism. Spatial
      and verbal memory were impaired in SCH patients (P < 0.05). TSH levels correlated
      negatively (P < 0.05) with these deficits. After LT4 replacement, verbal memory
      normalized. Spatial memory normalized in the SCH group but remained impaired in
      the hypothyroid group. Associative memory deficits persisted in the overt
      hypothyroid group. Hospital Anxiety and Depression Scale scores did not correlate
      with cognitive function. Measures of attention and response inhibition did not
      differ from control subjects. CONCLUSION: Cognitive impairment occurs in SCH and
      more markedly in overt hypothyroidism. These impairments appear predominantly
      mnemonic in nature, suggesting that the etiology is not indicative of general
      cognitive slowing. We propose that these deficits may reflect an underlying
      disruption of normal hippocampal function and/or connectivity.

PMID- 19584180
TI  - Association between C-reactive protein and adiposity in women.
AB  - CONTEXT: The link between C-reactive protein (CRP) and adiposity deserves to be
      further explored, considering the controversial diabetogenic role of CRP.
      OBJECTIVE: We explored the potential causal role of CRP on measures of adiposity.
      DESIGN: We used a Mendelian randomization approach with the CRP and LEPR genes as
      instrumental variables in a cross-sectional Caucasian population-based study
      comprising 2526 men and 2836 women. Adiposity was measured using body mass index
      (BMI), fat and lean mass estimated by bioelectrical impedance, and waist
      circumference. RESULTS: Log-transformed CRP explained by the rs7553007 single
      nucleotide polymorphism tagging the CRP gene was significantly associated with
      BMI [regression coefficient: 1.22 (0.18; 2.25), P = 0.02] and fat mass [2.67
      (0.65; 4.68), P = 0.01] but not with lean mass in women, whereas no association
      was found in men. Log-transformed CRP explained by the rs1805096 LEPR single
      nucleotide polymorphism was also positively associated, although not
      significantly, with BMI or fat mass. The combined CRP-LEPR instrument explained
      2.24 and 0.77% of CRP variance in women and men, respectively. Log-transformed
      CRP explained by this combined instrument was significantly associated with BMI
      [0.98 (0.32; 1.63), P = 0.004], fat mass [2.07 (0.79; 3.34), P = 0.001], and
      waist [2.09 (0.39; 3.78), P = 0.01] in women but not men. CONCLUSION: Our data
      suggest that CRP is causally and positively related to BMI in women and that this
      is mainly due to fat mass. Results on the combined CRP-LEPR instrument suggest
      that leptin may play a role in the causal association between CRP and adiposity
      in women. Results in men were not significant.

PMID- 19584179
TI  - Body mass index is associated with increased creatinine clearance by a mechanism
      independent of body fat distribution.
AB  - CONTEXT: Although obesity has been, in general, associated with glomerular
      hyperfiltration, visceral adiposity has been suggested to be associated with
      reduced glomerular filtration. OBJECTIVE: The aim of the study was to evaluate
      the differential effects of obesity and body fat distribution on glomerular
      filtration. DESIGN AND SETTING: We conducted a cross-sectional study of the
      Japanese-American community in Seattle, Washington. PARTICIPANTS: We studied a
      representative sample of second-generation Japanese-American men and women with
      normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired
      fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King
      County, Washington. MAIN OUTCOME MEASURES: Glomerular filtration rate was
      estimated by 24-h urinary creatinine clearance, body size by body mass index
      (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT
      scan. RESULTS: Creatinine clearance was positively correlated with BMI (r =
      0.429; P < 0.001), fasting glucose (r = 0.198; P = 0.001), and insulin levels (r
      = 0.125; P = 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P <
      0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between
      creatinine clearance and BMI remained significant after adjustments for IAF, SCF
      areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF
      areas were not independently associated with creatinine clearance after adjusting
      for BMI. Creatinine clearance increased with increasing BMI after adjusting for
      fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal
      glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r =
      0.471; P < 0.001). CONCLUSIONS: BMI rather than body fat distribution is an
      independent determinant of creatinine clearance in nondiabetic subjects. Lean
      body mass, rather than adiposity, may explain this association.

PMID- 19584181
TI  - Effect of vitamin D deficiency and replacement on endothelial function in
      asymptomatic subjects.
AB  - CONTEXT: Vitamin D receptors are present in many tissues. Hypovitaminosis D is
      considered to be a risk factor for atherosclerosis. OBJECTIVE: This study
      explores the effects of vitamin D replacement on insulin sensitivity, endothelial
      function, inflammation, oxidative stress, and leptin in vitamin D-deficient
      subjects. DESIGN, SETTING, AND PATIENTS: Twenty-three asymptomatic vitamin D
      deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter
      were compared with a control group that had a mean 25(OH)D level of 75
      nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3
      months. The following parameters were evaluated before and after treatment:
      vitamin D metabolites, leptin, endothelial function by brachial artery flow
      mediated dilatation (FMD), insulin sensitivity index based on oral glucose
      tolerance test, and lipid peroxidation as measures of thiobarbituric acid
      reactive substances (TBARS). RESULTS: FMD measurements were significantly lower
      in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after
      replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly
      lower than pretreatment levels (P < 0.001). A positive correlation between FMD
      and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and
      TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in
      leptin levels after therapy, and the leptin levels were positively correlated
      with 25(OH)D levels (r = 0.45; P < 0.05). CONCLUSIONS: This study shows that
      25(OH)D deficiency is associated with endothelial dysfunction and increased lipid
      peroxidation. Replacement of vitamin D has favorable effects on endothelial
      function. Vitamin D deficiency can be seen as an independent risk factor of
      atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may
      predispose to higher rates of cardiovascular disease in the winter.

PMID- 19584182
TI  - Association of plasma leptin concentrations with adiposity measurements in rural
      Chinese adolescents.
AB  - CONTEXT: There is evidence that leptin is involved in the etiology of obesity
      related cardiovascular disease in adults. This raises the question of whether
      leptin levels in adolescence are indicative of adiposity-related cardiovascular
      risk. OBJECTIVE: This study investigated gender-specific patterns of plasma
      leptin during adolescence, assessed which adiposity measurements are most
      strongly associated with plasma leptin, and estimated to what degree leptin
      adiposity associations are influenced by genetic factors. METHODS: Plasma leptin
      concentrations were determined using a sandwich immunoassay. Associations between
      plasma leptin and several adiposity measurements were examined using generalized
      estimating equations. Genetic contribution to leptin-adiposity association was
      estimated by Cholesky decomposition models using twin design. RESULTS: Plasma
      leptin levels were higher in females than males at all Tanner stages. In females,
      body mass index, waist circumference, fat mass index (FMI), and percentage body
      fat (%BF) had similar associations with leptin levels. In males, %BF and FMI were
      more strongly associated with leptin levels than body mass index and waist
      circumference. In both males and females, percentage trunk fat had the weakest
      association with leptin among the five adiposity measures. Shared genetic factors
      account for more than 80% of the phenotypic correlation between %BF and leptin.
      CONCLUSIONS: We found gender differences in leptin levels and leptin-adiposity
      associations. In both genders, leptin levels were strongly associated with %BF
      and FMI, particularly in males. Shared genetic factors contributed largely to the
      phenotypic correlation between leptin and %BF. Our findings underscored the
      importance of further investigation of leptin as a biomarker of adiposity in
      adolescents.

PMID- 19584183
TI  - Estimated glucose disposal rate in assessment of the metabolic syndrome and
      microvascular complications in patients with type 1 diabetes.
AB  - OBJECTIVE: The objective of the study was to quantify insulin resistance in type
      1 diabetes patients by estimated glucose disposal rate (eGDR), according to the
      presence or absence of the metabolic syndrome, and its relationship with chronic
      complications. DESIGN: This was a cross-sectional study in 91 patients with type
      1 immune-mediated diabetes managed at an outpatient endocrinology clinic. All
      participants were Caucasians aged 18 yr or older with type 1 diabetes duration of
      more than 6 months who had completed the study protocol. RESULTS: Twenty-nine
      patients met metabolic syndrome criteria, yielding a prevalence of 31.9%.
      Although no differences in insulin requirements were found between diabetic
      patients with and without metabolic syndrome, lower eGDR levels, indicating
      greater insulin resistance, were observed in metabolic syndrome patients compared
      with those without (6.19 +/- 1.5 mg/kg(-1) x min(-1) vs. 9.93 +/- 1.6 mg/kg(-1) x
      min(-1)) (P < 0.001). An eGDR level less than 8.77 mg/kg(-1) x min(-1) showed
      100% sensitivity and 85.2% specificity for metabolic syndrome diagnosis. All
      patients with diabetes complications had eGDR values below 8.16 mg/kg(-1) x min(
      1). eGDR level was significantly lower in patients with diabetic retinopathy
      (5.97 +/- 1.2 mg/kg(-1) x min(-1)), diabetic neuropathy (5.06 +/- 0.4 mg/kg(-1) x
      min(-1)), or diabetic nephropathy (5.79 +/- 1.5 mg/kg(-1) x min(-1)) compared
      with those without (9.38 +/- 2.0 mg/kg(-1) x min(-1), P < 0.001; 9.26 +/- 2.0
      mg/kg(-1) x min(-1), P < 0.001; and 9.19 +/- 2.2 mg/kg(-1) x min(-1), P < 0.001).
      CONCLUSIONS: Insulin resistance is common in type 1 diabetes patients and is
      associated with microvascular complications. eGDR, as an insulin resistance
      marker, provides more useful information than other classical variables such as
      insulin requirements.

PMID- 19584184
TI  - Timing of levothyroxine administration affects serum thyrotropin concentration.
AB  - CONTEXT: Patients treated with levothyroxine typically ingest it in a fasting
      state to prevent food impairing its absorption. The serum thyrotropin
      concentration is the therapeutic index of levothyroxine action. OBJECTIVE: The
      study objective was to determine the effect of the timing of levothyroxine
      administration in relationship to food on serum thyrotropin levels. DESIGN:
      Participants were randomized to one of six sequences, each consisting of three 8
      wk regimens in a three-period crossover design. These regimens were in a fasting
      state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and
      total T(3) during each of the three timing regimens were documented. The primary
      outcome was the difference between serum TSH concentrations under fasting
      conditions compared with concentrations during the other 8-wk regimens. SETTING:
      The study was conducted in an academic medical center. PARTICIPANTS: Study
      participants were receiving levothyroxine for treatment of hypothyroidism or
      thyroid cancer. RESULTS: Sixty-five patients completed the study. The mean
      thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was
      administered in the fasting state. When levothyroxine was taken with breakfast,
      the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29
      mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration
      was also significantly higher (2.19 +/- 2.66 mIU/liter). CONCLUSION: Nonfasting
      regimens of levothyroxine administration are associated with higher and more
      variable serum TSH concentrations. If a specific serum TSH goal is desired,
      thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion
      of levothyroxine ensures that TSH concentrations remain within the narrowest
      target range.

PMID- 19584185
TI  - Persistent adrenocorticotropin response to desmopressin in the early
      postoperative period predicts recurrence of Cushing's disease.
AB  - CONTEXT: Patients with Cushing's disease (CD) often show an ACTH and cortisol
      response to desmopressin (DDAVP). OBJECTIVE: We tested whether persistence of a
      positive response to DDAVP after successful surgery identifies patients at risk
      of CD recurrence. DESIGN: We prospectively included all CD patients who had a
      positive response to DDAVP before successful surgery from 1995 through 2007.
      SETTING: The study was performed at a university hospital. PATIENTS: One hundred
      seventy-four patients with CD, 148 women and 26 men, mean age 36.1 +/- 0.8 yr,
      were studied. The median follow-up after surgery was 58 months (interquartile
      range 22-93 months). INTERVENTION: DDAVP test was performed immediately before
      and after surgery. MAIN OUTCOME MEASURE: An ACTH and cortisol increment of at
      least 30 and 20% above baseline, respectively, were considered as a positive
      response to DDAVP. The risk of CD recurrence was analyzed according to the
      postoperative hormonal response to DDAVP. RESULTS: Recurrence of CD occurred in
      19 patients (10.9%). The recurrence-free survival at 5 yr was 89.8% [95%
      confidence interval (CI) 84.2-95.4]. Patients with a positive ACTH response had a
      5-yr recurrence-free survival of 82.6% (95% CI 70.6-94.6%) as compared with 94.0%
      (95% CI 88.2-99.8%; P < 0.01) in patients without it. Multivariate analysis
      showed that persistence of a positive ACTH response to DDAVP was significantly
      associated with CD recurrence. CONCLUSION: Positive ACTH response to DDAVP after
      surgery is associated with an increased risk of CD recurrence. However, the
      specificity and predictive value of this finding are low.

PMID- 19584186
TI  - Nonalcoholic fatty liver is not associated with carotid intima-media thickness in
      type 2 diabetic patients.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is commonly associated with
      obesity, metabolic syndrome, and type 2 diabetes. Several studies suggest that
      NAFLD is independently associated with an increased risk of cardiovascular
      disease in nondiabetic subjects. In type 2 diabetic subjects, the link between
      fatty liver and atherosclerosis is less clear. In this study, we set out to
      determine, whether fatty liver content, evaluated using 1H-magnetic resonance
      spectroscopy, a very precise imaging technique, was associated with
      atherosclerosis in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A
      total of 101 patients with type 2 diabetes mellitus were included in this study.
      Liver fat (1H-magnetic resonance spectroscopy) and carotid intima media thickness
      (IMT) were measured. RESULTS: Sixty-one (60.3%) patients had steatosis (hepatic
      triglyceride content greater than 5.5%). Liver fat content was correlated with
      fasting serum triglycerides (r = 0.22; P = 0.02) and alanine aminotransferase (r
      = 0.42; P = 0.0001). Sixty-eight percent of subjects with severe steatosis
      (hepatic triglyceride content greater than 15%) had aspartate aminotransferase in
      the normal range. Age was strongly correlated with IMT (r = 0.37; P = 0.0002).
      Steatosis did not correlate with IMT (r = -0.03; P = 0.75). There was no
      significant difference between the two groups (with and without hepatic
      steatosis) for IMT values. CONCLUSIONS: this study suggests that in people with
      type 2 diabetes, fatty liver is not associated with cardiovascular disease. In a
      diabetic population, it seems that fatty liver is not a determinant factor
      associated with carotid IMT.

PMID- 19584187
TI  - Growth hormone deficiency in patients with chronic heart failure and beneficial
      effects of its correction.
AB  - CONTEXT: A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF)
      has been described by several independent groups and is associated with poor
      clinical status and outcome. OBJECTIVE: The aim of the current study was to
      investigate the prevalence of GH deficiency in a patient population with CHF and
      evaluate the cardiovascular effects of GH replacement therapy. DESIGN AND
      SETTING: The randomized, single-blind, controlled trial was conducted at the
      Federico II University. PARTICIPANTS: One hundred fifty-eight patients with CHF,
      New York Heart Association class II-IV, underwent a GH stimulation test. Sixty
      three patients satisfied the criteria for GH deficiency, and 56 of them were
      enrolled in the trial. INTERVENTION: The treated group (n = 28) received GH at a
      replacement dose of 0.012 mg/kg every second day (approximately 2.5 IU). MAIN
      OUTCOMES MEASURES: Changes in physical performance and various cardiovascular
      indexes were measured. RESULTS: GH replacement therapy improved quality of life
      score (from 46 +/- 5 to 38 +/- 4; P < 0.01), increased peak oxygen uptake and
      exercise duration (from 12.9 +/- .9 to 14.5 +/- 1 ml/kg x min and from 520 +/- 36
      to 586 +/- 43 sec, respectively; P < 0.01), and flow-mediated vasodilation (from
      8.8 +/- 1.3 to 12.7 +/- 1.2%; P < 0.01). GH increased left ventricular ejection
      fraction (from 34 +/- 2 to 36 +/- 2%; P < 0.01) and reduced circulating N
      terminal pro-brain natriuretic peptide levels (from 3201 +/- 900 to 2177 +/- 720
      pg/ml; P = 0.006). No significant changes from baseline were observed in
      controls. CONCLUSIONS: As many as 40% of patients with CHF are GH deficient. GH
      replacement therapy in these patients improves exercise capacity, vascular
      reactivity, left ventricular function, and indices of quality of life.

PMID- 19584188
TI  - Impact of the exon 3-deleted growth hormone (GH) receptor polymorphism on
      baseline height and the growth response to recombinant human GH therapy in GH
      deficient (GHD) and non-GHD children with short stature: a systematic review and
      meta-analysis.
AB  - CONTEXT: The exon-3 deleted GH receptor (GHR(d3)) polymorphism is associated with
      an increased growth response to recombinant human GH (rhGH) therapy in some, but
      not all, studies in GH-deficient (GHD) and non-GHD children with short stature.
      OBJECTIVE: The aim of the study was to assess the effects of GHR(d3) on baseline
      height and the first year's growth response to rhGH treatment in prepubertal GHD
      and non-GHD children with short stature. DESIGN: We conducted a systematic review
      and meta-analysis. METHODS: Fifteen studies reporting the effect of GHR(d3) on
      growth parameters were included. Principal outcomes were baseline height sd score
      (SDS) and the weighted average of change in growth velocity (Delta cm/yr) and
      height gain (Delta height SDS) after 1 yr of rhGH. RESULTS: In GHD, not in non
      GHD, baseline height SDS was 0.159 sd higher [95% confidence interval (CI),
      0.020, 0.298] in GHR(d3) compared with GHR(wt-wt). In GHR(d3), rhGH therapy
      resulted in a higher increase in growth velocity (0.521 cm/yr; 95% CI, 0.196,
      1.015) and height gain (0.075 sd; 95% CI, 0.007, 0.143) compared with GHR(wt-wt).
      Meta-regression demonstrated a larger difference between GHR(d3) and GHR(wt-wt)
      in studies using lower rhGH doses and carried out at a higher age, independently
      of the cause of short stature. CONCLUSIONS: This meta-analysis in prepubertal
      children with short stature indicates that GHR(d3) is associated with increased
      baseline height in GHD, but not in non-GHD. Furthermore, GHR(d3) stimulates
      growth velocity by an additional effect of approximately 0.5 cm during the first
      year of rhGH treatment, and this effect is more pronounced at lower doses of rhGH
      and higher age.

PMID- 19584189
TI  - Antiresorptive effects of phytoestrogen supplements compared with estradiol or
      risedronate in postmenopausal women using (41)Ca methodology.
AB  - INTRODUCTION: Reduction of ovarian estrogen secretion at menopause increases net
      bone resorption and leads to bone loss. Isoflavones have been reported to protect
      bone from estrogen deficiency, but their modest effects on bone resorption have
      been difficult to measure with traditional analytical methods. METHODS: In this
      randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we
      compared four commercial sources of isoflavones from soy cotyledon, soy germ,
      kudzu, and red clover and a positive control of oral 1 mg estradiol combined with
      2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their
      antiresorptive effects on bone using novel (41)Ca methodology. RESULTS:
      Risedronate and estrogen plus progesterone decreased net bone resorption measured
      by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum
      isoflavone profiles indicating bioavailability of the phytoestrogens, only soy
      isoflavones from the cotyledon and germ significantly decreased net bone
      resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption
      and biochemical markers of bone turnover were not influenced by interventions.
      CONCLUSIONS: Dietary supplements containing genistein-like isoflavones
      demonstrated a significant but modest ability to suppress net bone resorption in
      postmenopausal women at the doses supplied in this study over a 50-d intervention
      period.

PMID- 19584190
TI  - Testosterone's short-term positive effect on luteinizing-hormone secretory-burst
      mass and its negative effect on secretory-burst frequency are attenuated in
      middle-aged men.
AB  - BACKGROUND: Testosterone (T) production declines and LH pulses become smaller and
      more frequent in middle-aged men. The mechanisms underlying these changes are not
      known. RATIONALE: Small frequent LH pulses in middle-aged men could reflect
      impaired feedback by systemic T. HYPOTHESIS: Middle age disrupts negative
      feedback by T on selected facets of LH secretion. SUBJECTS AND SETTING: Healthy
      men were studied at an academic medical center. METHODS: The protocol comprised
      blockade of gonadal steroidogenesis and graded transdermal addback of T doses of
      0, 2.5, 5, or 7.5 mg/d designed to span the castrate to physiological range of T
      concentrations in each of 23 healthy men ages 19-71 yr (interquartile range, 28
      53 yr). We quantified 12-h basal and pulsatile LH secretion (92 time series)
      using a mathematically justified deconvolution method. RESULTS: Stepwise T
      supplementation from the hypogonadal through the eugonadal range repressed mean
      (12-h) LH concentrations (P = 0.001). By regression analysis, age attenuated the
      capabilities of increasing T concentrations to 1) increase LH secretory-burst
      mass (P < 0.0001); and 2) decrease LH secretory-burst frequency (P = 0.025). Age
      did not alter T's feedback on basal LH secretion, interpulse regularity, the
      waveform of LH secretory bursts, or the slow half-life of LH. CONCLUSION: Middle
      age impairs both the positive and negative actions of systemic T on pulsatile LH
      secretion in healthy men, thus potentially explaining earlier inconsistencies in
      feedback studies based upon single-sample mean LH concentrations. Longitudinal
      studies will be required to elucidate the precise age dependence of inferred dual
      feedback failure.

PMID- 19584192
TI  - Effects of teriparatide in postmenopausal women with osteoporosis on prior
      alendronate or raloxifene: differences between stopping and continuing the
      antiresorptive agent.
AB  - OBJECTIVE: The aim of the study was to assess adding vs. switching to
      teriparatide 20 microg/d in patients on alendronate or raloxifene. DESIGN: We
      conducted a randomized, open-label trial. PATIENTS AND INTERVENTIONS:
      Postmenopausal women with osteoporosis on alendronate or raloxifene for at least
      18 months added teriparatide (Add groups) or switched to teriparatide (Switch
      groups) for 18 months. MAIN OUTCOME MEASURES: We measured bone turnover markers
      (BTM) and bone mineral density (BMD). RESULTS: In the alendronate stratum,
      increases in BTM were smaller in the Add vs. Switch group [6-month PINP (64 vs.
      401%); bone ALP (15 vs. 71%); betaCTX (27 vs. 250%); all P < 0.001]. However, at
      6 months, total hip BMD increased more in the Add vs. Switch group (1.4 vs. 
      0.8%; P = 0.002). In the Add vs. Switch group, 18-month BMD increments were
      higher in lumbar spine (8.4 vs. 4.8%; P = 0.003) and total hip (3.2 vs. 0.9%; P =
      0.02), but not in femoral neck (2.7 vs. 2.3%; P = 0.75). In the raloxifene
      stratum, increases in BTM were also smaller in the Add vs. Switch group [6-month
      PINP (131 vs. 259%; P < 0.001), bone ALP (31 vs. 44%; P = 0.035), and betaCTX (67
      vs. 144%; P = 0.001)]. At 6 months, total hip BMD increase was greater in the Add
      vs. Switch group (1.8 vs. 0.5%; P = 0.028). At 18 months, increases in lumbar
      spine (9.2 vs. 8.1%), total hip (2.8 vs. 1.8%), and femoral neck (3.8 vs. 2.2%)
      were not significantly different between groups. CONCLUSIONS: In women with
      osteoporosis treated with antiresorptives, greater bone turnover increases were
      achieved by switching to teriparatide, whereas greater BMD increases were
      achieved by adding teriparatide.

PMID- 19584194
TI  - Regulation of soluble vascular endothelial growth factor receptor 1 secretion
      from human endothelial cells by tissue inhibitor of metalloproteinase 1.
AB  - Vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) are
      key regulators in human ovarian angiogenesis. Produced by granulosa and ovarian
      theca interna cells, VEGF promotes blood vessel growth during follicular
      development and corpus luteum formation, whereas sVEGFR-1, which is secreted by
      endothelial cells, functions as an antagonist to VEGF activity by binding it. In
      order to gain further insights into the regulatory mechanisms of ovarian
      angiogenesis, the aim of the present study was to analyze the influence of tissue
      inhibitor of metalloproteinase 1 (TIMP-1), which is actively involved in the
      degradation and remodeling of the extracellular matrix, on sVEGFR-1 secretion of
      cultured human umbilical vein endothelial cells. sVEGFR-1 production was
      determined in the culture supernatant by Sandwich-ELISA. We showed that TIMP-1
      produced by human granulosa cells and recombinant human TIMP-1 both significantly
      increased the production of sVEGFR-1 in endothelial cells. Also, the down
      regulation of TIMP-1 expression by RNA interference resulted in a significant
      reduction of endothelial sVEGFR-1 secretion into the culture medium. Furthermore,
      TIMP-1 weakly inhibited proliferation of VEGF-stimulated endothelial cells. In
      conclusion, our results provide evidence that TIMP-1 increases the production of
      sVEGFR-1 in endothelial cells and thus may reduce VEGF bioavailability, leading
      to reduced blood vessel growth in the ovary.

PMID- 19584193
TI  - Subtle alterations of cardiac performance in children with growth hormone
      deficiency: results of a two-year prospective, case-control study.
AB  - BACKGROUND: GH-deficient (GHD) children have reduced left ventricular (LV) mass,
      but impairment of cardiac function has never been documented. AIM: The aim of the
      study was to evaluate effects of GHD and GH therapy on cardiac function using
      load-dependent and load-independent indices of myocardial contractility. PATIENTS
      AND METHODS: Echocardiography was performed in 24 GHD children at baseline and 1
      and 2 yr after GH therapy and in 24 controls. RESULTS: Compared with controls,
      GHD children at baseline had lower LV mass (LV mass/BSA 50.6 +/- 1.8 vs. 60.5 +/-
      2.4 g/m(2); P < 0.002, and LV mass/H(2.7) 28.7 +/- 1.2 vs. 33.6 +/- 1.3 g/m(2.7);
      P < 0.009). Global systolic function was normal, with only a trend toward slight
      impairment of the fractional shortening (34.9 +/- 1.5 vs. 37.6 +/- 1.1%).
      However, subtle LV dysfunction was revealed by load-dependent and load
      independent indices of myocardial contractility. In fact, GHD patients compared
      with controls showed lower rate-corrected mean velocity of circumferential fiber
      shortening (1.0 +/- 0.03 vs. 1.18 +/- 0.03 circ/sec; P = 0.0001) and stress
      shortening index (0.10 +/- 0.02 vs. 0.18 +/- 0.02; P < 0.007) and higher end
      systolic stress (49.2 +/- 1.4 vs. 45.7 +/- 1.0 g/cm(2); P < 0.05). One year of GH
      treatment was associated with a significant improvement of cardiac size (LV
      mass/BSA 67.8 +/- 2.9 g/m(2); LV mass/H(2.7) 38.2 +/- 2.0 g/m(2.7); P < 0.0001
      and P = 0.0003, respectively) and myocardial contractility (mean velocity of
      circumferential fiber shortening 1.2 +/- 0.04 circ/sec; P < 0.0002; stress
      shortening index 0.19 +/- 0.02; P < 0.003) and reduced afterload (end-systolic
      stress 43.9 +/- 1.4 g/cm(2); P < 0.03). CONCLUSIONS: Our data indicate that GH
      deficiency is associated with abnormalities in morphology and function in not
      only adults but also children and further supports the beneficial effect of GH on
      the heart.

PMID- 19584191
TI  - Insulin resistance in adolescents with type 2 diabetes is associated with
      impaired exercise capacity.
AB  - CONTEXT: The incidence of pediatric type 2 diabetes (T2D) is rising, with unclear
      effects on the cardiovascular system. Cardiopulmonary fitness, a marker of
      morbidity and mortality, is abnormal in adults with T2D, yet the mechanisms are
      incompletely understood. OBJECTIVE: We hypothesized that cardiopulmonary fitness
      would be reduced in youth with T2D in association with insulin resistance (IR)
      and cardiovascular dysfunction. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      cross-sectional study at an academic hospital that included 14 adolescents (age
      range, 12-19 yr) with T2D, 13 equally obese adolescents and 12 lean adolescents
      similar in age, pubertal stage, and activity level. MAIN OUTCOME MEASURES:
      Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and
      oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac
      function by echocardiography, vascular function by venous occlusion
      plethysmography, body composition by dual-energy x-ray absorptiometry,
      intramyocellular lipid by magnetic resonance spectroscopy, and inflammation by
      serum markers. RESULTS: Adolescents with T2D had significantly decreased
      VO(2)peak and insulin sensitivity, and increased soleus intramyocellular lipid, C
      reactive protein, and IL-6 compared to obese or lean adolescents. Adolescents
      with T2D also had significantly prolonged VO(2)kinetics, decreased work rate,
      vascular reactivity, and adiponectin, and increased left ventricular mass and
      fatty acids compared to lean adolescents. In multivariate linear regression
      analysis, IR primarily, and fasting free fatty acids and forearm blood flow
      secondarily, were significant independent predictors of VO(2)peak. CONCLUSIONS:
      Given the strong relationship between decreased cardiopulmonary fitness and
      increased mortality, these findings in children are especially concerning and
      represent early signs of impaired cardiac function.

PMID- 19584196
TI  - Update on nonautoimmune diabetes in children.
AB  - Over the last two decades, nonautoimmune-mediated type 2 diabetes mellitus (T2DM)
      has become a clinical entity of increasing importance among adolescents. Yet,
      research specific to adolescent T2DM is in its infancy. Our understanding of the
      epidemiology of T2DM among adolescents is complicated by variability in
      definition, incomplete knowledge of novel autoimmune epitopes, the presence of
      individuals with phenotypic overlap between type 1 and type 2 diabetes, and
      inadequate understanding of the contribution of common single-gene defects.
      Furthermore, a higher ratio of diagnosed to undiagnosed cases and a strong
      relationship with the onset of puberty suggest unique aspects of the
      pathophysiology in adolescents. Investigators have begun to address these areas
      while also identifying important relationships with the intrauterine development.
      Well-designed clinical studies are currently examining the adolescent-specific
      challenges in prevention and treatment of T2DM, whereas a number of associations
      struggle to provide screening and treatment guidelines to practitioners based on
      limited understanding of the phenomenon. Finally, there is growing understanding
      of medium- and long-term morbidity and mortality in early adulthood. Given the
      likelihood that early-onset T2DM will have important implications for future
      public health, continued attention to all aspects of this complex social,
      economic, and physiological disorder is critical.

PMID- 19584197
TI  - Dopamine agonist therapy in prolactinomas: when can treatment be discontinued?

PMID- 19584195
TI  - Oogenesis and cell death in human prenatal ovaries: what are the criteria for
      oocyte selection?
AB  - Prenatal oogenesis produces hundreds of thousands of oocytes, most of which are
      discarded through apoptosis before birth. Despite this large-scale selection, the
      survivors do not constitute a perfect population, and the factors at the cellular
      level that result in apoptosis or survival of any individual oocyte are largely
      unknown. What then are the selection criteria that determine the size and quality
      of the ovarian reserve in women? This review focuses on new data at the cellular
      level, on human prenatal oogenesis, offering clues about the importance of the
      timing of entry to meiotic prophase I by linking the stages and progress through
      MPI with the presence or absence of apoptotic markers. The characteristics and
      responsiveness of cultured human fetal ovarian tissue at different gestational
      ages to growth factor supplementation and the impact of meiotic abnormalities
      upon apoptotic markers are discussed. Future work will require the use of a
      tissue culture model of prenatal oogenesis in order to investigate the fate of
      individual live oocytes at different stages of development.

PMID- 19584198
TI  - Polycystic ovary syndrome: a model of combinatorial endocrinology?

PMID- 19584199
TI  - Preeclampsia and soluble fms-like tyrosine kinase 1.

PMID- 19584200
TI  - Central NMU signaling in body weight and energy balance regulation: evidence from
      NMUR2 deletion and chronic central NMU treatment in mice.
AB  - To investigate the role of the central neuromedin U (NMU) signaling system in
      body weight and energy balance regulation, we examined the effects of long-term
      intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking
      the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6
      mice, icv infusion of NMU (8 microg x day(-1) x mouse(-1)) for 7 days decreased
      body weight and total energy intake compared with vehicle treatment. However,
      these parameters were unaffected by NMU treatment in lean male and female C57BL/6
      mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had
      increased body weight and body fat mass when fed a high-fat diet but lacked a
      clear body weight phenotype when fed a standard diet compared with wild-type
      littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat
      diet were protected from central NMU-induced body weight loss compared with
      littermate wild-type mice. Thus, we provide the first evidence that long-term
      central NMU treatment reduces body weight, food intake, and adiposity and that
      central NMUR2 signaling is required for these effects in female but not male
      mice.

PMID- 19584202
TI  - The syndrome of combined pulmonary fibrosis and emphysema.

PMID- 19584201
TI  - A highly energetic process couples calcium influx through L-type calcium channels
      to insulin secretion in pancreatic beta-cells.
AB  - Calcium (Ca(2+)) influx is required for the sustained secretion of insulin and is
      accompanied by a large rate of energy usage. We hypothesize that the energy usage
      reflects a process [Ca(2+)/metabolic coupling process (CMCP)] that couples Ca(2+)
      to insulin secretion by pancreatic islets. The aim of the study was to test this
      hypothesis by testing the effect of inhibiting candidate Ca(2+)-sensitive
      proteins proposed to play a critical role in the CMCP. The effects of the
      inhibitors on oxygen consumption rate (OCR), a reflection of ATP usage, and
      insulin secretion rate (ISR) were compared with those seen when L-type Ca(2+)
      channels were blocked with nimodipine. We reasoned that if a downstream Ca(2+)
      regulated site was responsible for the OCR associated with the CMCP, then its
      inhibition should mimic the effect of nimodipine. Consistent with previous
      findings, nimodipine decreased glucose-stimulated OCR by 36% and cytosolic Ca(2+)
      by 46% and completely suppressed ISR in rat pancreatic islets. Inhibitors of
      three calmodulin-sensitive proteins (myosin light-chain kinase, calcineurin, and
      Ca(2+)/calmodulin-dependent protein kinase II) did not meet the criteria. In
      contrast, KN-62 severed the connection between Ca(2+) influx, OCR, and ISR
      without interfering with Ca(2+) influx. In the presence of nimodipine or KN-62,
      potentiators of ISR, acetylcholine, GLP-1, and arginine had little effect on
      insulin secretion, suggesting that the CMCP is also essential for the
      amplification of ISR. In conclusion, a KN-62-sensitive process directly mediates
      the effects of Ca(2+) influx via L-type Ca(2+) channels on OCR and ISR,
      supporting the essential role of the CMCP in mediating ISR.

PMID- 19584203
TI  - The metabolic syndrome and pulmonary vascular disease.

PMID- 19584204
TI  - Stimulating advances in chronic heart failure and COPD.

PMID- 19584205
TI  - Lung cancer staging and the home insurance building constructed in 1884-1885.

PMID- 19584207
TI  - The role of conflict of interest in reporting of scientific information.
AB  - We have come to appreciate that scientific misconduct is often not intuitively
      obvious to those who perpetrate it. Therefore, this commentary has been written
      to review what we know about the role of conflict of interest (COI) in the
      reporting of scientific information and to challenge those of us in educator
      roles to do a better job in mentoring our trainees, junior faculty, and
      associates on what is right and wrong; what is ethical and unethical. The review
      addresses the following questions: (1) Why has the public trust in the clinical
      research industry been eroded? (2) How often is the ethical concept of equipoise
      violated in industry-sponsored randomized controlled clinical trials? (3) How
      often are negative trials underreported and favorable trials selectively or
      redundantly over-reported in industry-sponsored randomized controlled clinical
      trials? (4) What is being done to restore the public trust? While there are
      multiple strategies to mitigate COI in the reporting of scientific information,
      we have come to appreciate that the disclosure of potential conflicts of interest
      is not enough. It is our hope that this article and its contents can serve as a
      stimulus for the development and incorporation of an educational series in all
      training programs on what is ethical and unethical in the conducting and
      reporting of scientific studies.

PMID- 19584208
TI  - The new lung cancer staging system.
AB  - The International Association for the Study of Lung Cancer (IASLC) has conducted
      an extensive initiative to inform the revision of the lung cancer staging system.
      This involved development of an international database along with extensive
      analysis of a large population of patients and their prognoses. This article
      reviews the recommendations of the IASLC International Staging Committee for the
      definitions for the TNM descriptors and the stage grouping in the new non-small
      cell lung cancer staging system.

PMID- 19584209
TI  - Recombinant activated factor VII for massive hemoptysis in patients with cystic
      fibrosis.
AB  - Massive hemoptysis is a common complication in patients with cystic fibrosis (CF)
      and is associated with significant morbidity and mortality. Conventional
      treatment with antibiotic therapy and early bronchial artery embolization (BAE)
      is usually successful in achieving hemostasis in the majority of patients.
      Recombinant activated factor VII (rFVIIa), originally developed for use in
      patients with hemophilia, has emerged as a general hemostatic agent that is
      potentially useful in the management of many life-threatening bleeding
      conditions. In this article, we present four patients with CF lung disease and
      massive hemoptysis who were treated successfully with rFVIIa. We suggest that in
      patients with CF who present with massive hemoptysis, the use of rFVIIa can be
      considered in patients with refractory hemoptysis despite conventional therapy or
      as a temporizing therapy when BAE is not immediately available.

PMID- 19584210
TI  - Spontaneous middle lobe torsion secondary to pleural effusion.
AB  - Pulmonary torsion is very rare, and usually occurs following lung resection. We
      report a case of spontaneous middle lobe torsion in a patient presenting with a
      right pleural effusion. The condition was treated by lobectomy through a totally
      thoracoscopic approach.

PMID- 19584211
TI  - Sleep in the ICU: potential mechanisms and clinical implications.
AB  - Patients in the ICU are known to have severely disrupted sleep with disturbed
      circadian pattern, decreased nocturnal sleep time, abnormally increased stages 1
      and 2 sleep, and reduced or absent deep sleep. Recent data reveal that a
      subpopulation of critically ill patients manifests unique EEG sleep patterns. The
      etiology of sleep disruption in the ICU includes the inherent nature of the
      environment, medications, ventilator-patient interaction, and the effect of acute
      illness. How sleep disruption contributes to outcomes in critically ill patients,
      such as recovery time and weaning from mechanical ventilation, is unknown. This
      article reviews the literature describing sleep in ICU patients, including recent
      investigations in patients who require mechanical ventilation, factors that
      affect sleep in critically ill patients, and the potential mechanisms and
      clinical implications of disturbed sleep in the ICU setting with directions to
      consider for future investigations.

PMID- 19584212
TI  - Reporting "basic results" in ClinicalTrials.gov.

PMID- 19584213
TI  - Update on Registration of Clinical Trials in ClinicalTrials.gov.

PMID- 19584214
TI  - A rare cause of multiple cavitary nodules.

PMID- 19584215
TI  - A 38-year-old welder with dyspnea and iron overload.

PMID- 19584216
TI  - An iatrogenic lung nodule.

PMID- 19584220
TI  - Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of
      ventilator-associated pneumonia.

PMID- 19584221
TI  - Surfactant replacement therapy in ARDS.

PMID- 19584222
TI  - Perioperative epidural analgesia and prevention of ventilator-associated
      pneumonia.

PMID- 19584223
TI  - Steroids in patients with septic shock.

PMID- 19584224
TI  - Discordance in spirometric interpretations using different reference equations.

PMID- 19584225
TI  - Miller-Fisher variant of Guillain-Barre syndrome.

PMID- 19584226
TI  - Impact of pulmonary tuberculosis on menstrual pattern and fertility.

PMID- 19584227
TI  - Biological properties of potent inhibitors of class I phosphatidylinositide 3
      kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.
AB  - The phosphatidylinositide 3-kinase pathway is frequently deregulated in human
      cancers and inhibitors offer considerable therapeutic potential. We previously
      described the promising tricyclic pyridofuropyrimidine lead and chemical tool
      compound PI-103. We now report the properties of the pharmaceutically optimized
      bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting
      clinical development candidate GDC-0941. All four compounds inhibited
      phosphatidylinositide 3-kinase p110alpha with IC(50) < or = 10 nmol/L. Despite
      some differences in isoform selectivity, these agents exhibited similar in vitro
      antiproliferative properties to PI-103 in a panel of human cancer cell lines,
      with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and
      comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620
      exhibited improvements in solubility and metabolism with high tissue distribution
      in mice. Both compounds gave improved antitumor efficacy over PI-103, following
      i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with
      treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI
      540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed
      comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and
      exhibited 78% oral bioavailability in mice, with tumor exposure above 50%
      antiproliferative concentrations for >8 hours following 150 mg/kg p.o. and
      sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led
      to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at
      150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV
      1 ovarian cancer xenografts, respectively. Together, these data support the
      development of GDC-0941 as a potent, orally bioavailable inhibitor of
      phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical
      trials.

PMID- 19584228
TI  - Increased antitumor activity of bevacizumab in combination with hypoxia inducible
      factor-1 inhibition.
AB  - Inhibition of hypoxia inducible factor-1 (HIF-1) is an attractive therapeutic
      strategy to target the tumor microenvironment. However, HIF-1 inhibitors may have
      limited activity as single agents and combination therapies may be required. We
      tested the hypothesis that HIF-1 inhibition in a hypoxic-stressed tumor
      microenvironment, which could be generated by administration of antiangiogenic
      agents, may result in a more pronounced therapeutic effect. The activity of
      bevacizumab, either alone or in combination with the HIF-1alpha inhibitor
      topotecan, was evaluated in U251-HRE xenografts. Tumor tissue was collected at
      the end of treatment and changes in tumor oxygenation, angiogenesis,
      proliferation, apoptosis, HIF-1alpha levels, HIF-1 target genes, and DNA damage
      were evaluated. Bevacizumab decreased microvessel-density and increased
      intratumor-hypoxia, but did not induce apoptosis. Moreover, bevacizumab alone
      caused a significant increase of HIF-1-dependent gene expression in tumor tissue.
      Addition of a low dose of daily topotecan to bevacizumab significantly inhibited
      tumor growth, relative to mice treated with topotecan or bevacizumab alone (P <
      0.01). The addition of topotecan to bevacizumab was also associated with profound
      inhibition of HIF-1 transcriptional activity, significant inhibition of
      proliferation, and induction of apoptosis. Importantly, DNA damage induced by
      topotecan alone was not augmented by addition of bevacizumab, suggesting that
      increased cytotoxic activity did not account for the increased antitumor effects
      observed. These results strongly suggest that combination of anti-vascular
      endothelial growth factor antibodies with HIF-1 inhibitors is an attractive
      therapeutic strategy targeting in the hypoxic tumor microenvironment.

PMID- 19584229
TI  - Evaluation of current methods used to analyze the expression profiles of ATP
      binding cassette transporters yields an improved drug-discovery database.
AB  - The development of multidrug resistance (MDR) to chemotherapy remains a major
      challenge in the treatment of cancer. Resistance exists against every effective
      anticancer drug and can develop by multiple mechanisms. These mechanisms can act
      individually or synergistically, leading to MDR, in which the cell becomes
      resistant to a variety of structurally and mechanistically unrelated drugs in
      addition to the drug initially administered. Although extensive work has been
      done to characterize MDR mechanisms in vitro, the translation of this knowledge
      to the clinic has not been successful. Therefore, identifying genes and
      mechanisms critical to the development of MDR in vivo and establishing a reliable
      method for analyzing highly homologous genes from small amounts of tissue is
      fundamental to achieving any significant enhancement in our understanding of MDR
      mechanisms and could lead to treatments designed to circumvent it. In this study,
      we use a previously established database that allows the identification of lead
      compounds in the early stages of drug discovery that are not ATP-binding cassette
      (ABC) transporter substrates. We believe this can serve as a model for appraising
      the accuracy and sensitivity of current methods used to analyze the expression
      profiles of ABC transporters. We found two platforms to be superior methods for
      the analysis of expression profiles of highly homologous gene superfamilies. This
      study also led to an improved database by revealing previously unidentified
      substrates for ABCB1, ABCC1, and ABCG2, transporters that contribute to MDR.

PMID- 19584230
TI  - Response prediction to a multitargeted kinase inhibitor in cancer cell lines and
      xenograft tumors using high-content tyrosine peptide arrays with a kinetic
      readout.
AB  - Multitargeted kinase inhibitors have shown clinical efficacy in a range of cancer
      types. However, two major problems associated with these drugs are the low
      fraction of patients for which these treatments provide initial clinical benefit
      and the occurrence of resistance during prolonged therapy. Several types of
      predictive biomarkers have been suggested, such as expression level and
      phosphorylation status of the major targeted kinase(s), mutational status of the
      kinases involved and of key components of the downstream signaling cascades, and
      gene expression signatures. In this work, we describe the development of a
      response prediction platform that does not require prior knowledge of the
      relevant kinases targeted by the inhibitor; instead, a phosphotyrosine peptide
      profile using peptide arrays with a kinetic readout is derived in lysates in the
      presence and absence of a kinase inhibitor. We show in a range of cell lines and
      in xenograft tumors that this approach allows for the stratification of
      responders and nonresponders to a multitargeted kinase inhibitor.

PMID- 19584231
TI  - EGFRvIII and c-Met pathway inhibitors synergize against PTEN-null/EGFRvIII+
      glioblastoma xenografts.
AB  - Receptor tyrosine kinase (RTK) systems, such as hepatocyte growth factor (HGF)
      and its receptor c-Met, and epidermal growth factor receptor (EGFR), are
      responsible for the malignant progression of multiple solid tumors. Recent
      research shows that these RTK systems comodulate overlapping and dynamically
      adaptable oncogenic downstream signaling pathways. This study investigates how
      EGFRvIII, a constitutively active EGFR deletion mutant, alters tumor growth and
      signaling responses to RTK inhibition in PTEN-null/HGF(+)/c-Met(+) glioma
      xenografts. We show that a neutralizing anti-HGF monoclonal antibody (L2G7)
      potently inhibits tumor growth and the activation of Akt and mitogen-activated
      protein kinase (MAPK) in PTEN-null/HGF(+)/c-Met(+)/EGFRvIII(-) U87 glioma
      xenografts (U87wt). Isogenic EGFRvIII(+) U87 xenografts (U87-EGFRvIII), which
      grew five times more rapidly than U87-wt xenografts, were unresponsive to
      EGFRvIII inhibition by erlotinib and were only minimally responsive to anti-HGF
      monoclonal antibodies. EGFRvIII expression diminished the magnitude of Akt
      inhibition and completely prevented MAPK inhibition by L2G7. Despite the lack of
      response to L2G7 or erlotinib as single agents, their combination synergized to
      produce substantial antitumor effects (inhibited tumor cell proliferation,
      enhanced apoptosis, arrested tumor growth, prolonged animal survival), against
      subcutaneous and orthotopic U87-EGFRvIII xenografts. The dramatic response to
      combining HGF:c-Met and EGFRvIII pathway inhibitors in U87-EGFRvIII xenografts
      occurred in the absence of Akt and MAPK inhibition. These findings show that
      combining c-Met and EGFRvIII pathway inhibitors can generate potent antitumor
      effects in PTEN-null tumors. They also provide insights into how EGFRvIII and c
      Met may alter signaling networks and reveal the potential limitations of certain
      biochemical biomarkers to predict the efficacy of RTK inhibition in genetically
      diverse cancers.

PMID- 19584232
TI  - Topoisomerase I levels in the NCI-60 cancer cell line panel determined by
      validated ELISA and microarray analysis and correlation with indenoisoquinoline
      sensitivity.
AB  - Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level
      of Top1 in tumors has been used as a biomarker for chemotherapeutic efficacy. In
      this study, we report the development and validation of a two-site enzyme
      chemiluminescent immunoassay for Top1, which we used to measure Top1 levels in
      the NCI-60 cancer cell line panel. Top1 levels ranged from 0.9 to 9.8
      ng/mL/microg protein extract in these cell lines. Levels varied both within and
      between cancer types but were generally highest in colon cancer and leukemia cell
      lines and lowest in central nervous system and renal cancer cell lines. Top1 mRNA
      levels in the NCI-60 cell lines were also measured by microarray; mRNA values
      generally showed a good correlation with protein levels (Pearson correlation =
      0.8). When these expression levels were compared with the activity of the
      indenoisoquinoline class of Top1 inhibitors across the NCI-60 cell panel, low
      levels of Top1 were associated with increased resistance to these drugs. The
      results of our studies indicate that our Top1 assay can be used to quantify Top1
      levels in untreated cells as well as cells treated with Top1 inhibitors and that
      the assay has the potential to be adapted for use in predicting clinical response
      to Top1-active antineoplastic agents.

PMID- 19584233
TI  - Determinants for the efficiency of anticancer drugs targeting either Aurora-A or
      Aurora-B kinases in human colon carcinoma cells.
AB  - The mitotic Aurora kinases, including Aurora-A and Aurora- B, are attractive
      novel targets for anticancer therapy, and inhibitory drugs have been developed
      that are currently undergoing clinical trials. However, the molecular mechanisms
      how these drugs induce tumor cell death are poorly understood. We have addressed
      this question by comparing the requirements for an efficient induction of
      apoptosis in response to MLN8054, a selective inhibitor of Aurora-A, and the
      selective Aurora-B inhibitor ZM447439 in human colon carcinoma cells. By using
      various isogenic knockout as well as inducible colon carcinoma cell lines, we
      found that treatment with MLN8054 induces defects in mitotic spindle assembly,
      which causes a transient spindle checkpoint-dependent mitotic arrest. This cell
      cycle arrest is not maintained due to the activity of MLN8054 to override the
      spindle checkpoint. Subsequently, MLN8054-treated cells exit from mitosis and
      activate a p53-dependent postmitotic G(1) checkpoint, which subsequently induces
      p21 and Bax, leading to G(1) arrest followed by the induction of apoptosis. In
      contrast, inhibition of Aurora-B by ZM447439 also interferes with normal
      chromosome alignment during mitosis and overrides the mitotic spindle checkpoint
      but allows a subsequent endoreduplication, although ZM447439 potently activates
      the p53-dependent postmitotic G(1) checkpoint. Moreover, the ZM447439-induced
      endoreduplication is a prerequisite for the efficiency of the drug. Thus, our
      results obtained in human colon carcinoma cells indicate that although both
      Aurora kinase inhibitors are potent inducers of tumor cell death, the pathways
      leading to the induction of apoptosis in response to these drugs are distinct.

PMID- 19584234
TI  - Pertuzumab increases epidermal growth factor receptor down-regulation by
      counteracting epidermal growth factor receptor-ErbB2 heterodimerization.
AB  - Epidermal growth factor receptor (EGFR) and ErbB2 readily form heterodimers when
      both are expressed in the same cell and the EGFR is activated by one of its
      ligands. Our data show that such heterodimers are constitutively formed also in a
      ligand-independent manner on overexpression of EGFR and ErbB2 in porcine aortic
      endothelial cells. Interestingly, cross-linking experiments showed that
      incubation with the antibody pertuzumab, which has been shown to bind the
      dimerization arm of ErbB2, resulted in dissolution of EGFR-ErbB2 heterodimers.
      Incubation with pertuzumab also increased the amount of EGF-induced EGFR
      homodimers, and under these conditions, endocytosis of radiolabeled EGF was
      increased. This increase was significant, although slightly more EGF was
      internalized in cells expressing EGFR only compared with pertuzumab-treated cells
      expressing both EGFR and ErbB2. By confocal microscopy analysis, more EGF was
      observed in endosomes on incubation with pertuzumab, and under similar
      conditions, immunoblotting experiments showed increased EGFR degradation on
      incubation with both EGF and pertuzumab. These results show that pertuzumab
      enhanced the endocytic down-regulation of EGFR by counteracting EGFR-ErbB2
      heterodimerization. Our previous results showing that ErbB2 counteracts EGFR
      endocytosis can therefore be explained by tethering of EGFR to ErbB2 at the
      plasma membrane.

PMID- 19584235
TI  - Induction of glutathione-dependent DNA double-strand breaks by the novel
      anticancer drug brostallicin.
AB  - Brostallicin is a DNA minor groove binder in phase II clinical trials. Here, we
      show that brostallicin induces gamma-H2AX nuclear foci that colocalize with 53BP1
      and are dependent on glutathione, as shown by inhibition of those gamma-H2AX foci
      by l-buthionine sulfoximine. To differentiate brostallicin from the clinically
      approved minor groove binder trabectedin (ecteinascidin 743), we tested whether
      the brostallicin-induced gamma-H2AX and antiproliferative responses were
      dependent on nucleotide excision repair and found that, unlike trabectedin, they
      are not. Additionally, brostallicin retained activity in the trabectedin
      resistant HCT116-ER5 cell line. Induction of gamma-H2AX foci by brostallicin was
      partially dependent on the repair nuclease Mre11. Pretreatment with aphidicolin
      partially reduced brostallicin-induced gamma-H2AX foci, suggesting that
      brostallicin induces both replication-associated and replication-independent DNA
      damage. Replication-associated DNA damage was further shown by the colocalization
      of gamma-H2AX foci with replication foci and by the rapid inhibition of DNA
      synthesis and accumulation of cells in S phase in response to brostallicin. In
      addition, brostallicin was able to induce lower intensity gamma-H2AX foci in
      human circulating lymphocytes. Together, our results indicate that brostallicin
      induces DNA double-strand breaks and suggest gamma-H2AX as a pharmacodynamic
      biomarker for brostallicin.

PMID- 19584236
TI  - EB1089 inhibits the parathyroid hormone-related protein-enhanced bone metastasis
      and xenograft growth of human prostate cancer cells.
AB  - Parathyroid hormone-related protein (PTHrP) plays a major role in prostate
      carcinoma progression and bone metastasis. Once prostate cancers become androgen
      independent, treatment options become limited. Vitamin D analogues represent a
      potentially valuable class of agents in this clinical context. Using the prostate
      cancer cell line C4-2 as a model, we studied the effects of PTHrP and the
      noncalcemic vitamin D analogue EB1089 on markers of prostate cancer cell
      progression in vitro and in vivo. C4-2 is a second-generation androgen
      independent LNCaP subline that metastasizes to the lymph nodes and bone when
      injected into nude mice and produces mixed lytic/blastic lesions, mimicking the
      in vivo situation. We report that PTHrP increases cell migration and invasion,
      and that a pathway via which EB1089 inhibits these processes is through down
      regulation of PTHrP expression. PTHrP also increases anchorage-independent cell
      growth in vitro and xenograft growth in vivo; EB1089 reverses these effects. The
      in vivo PTHrP effects are accompanied by increased tumor cell proliferation and
      survival. Treatment with EB1089 reverses the proliferative but not the
      antiapoptotic effects of PTHrP. PTHrP also increases intratumor vessel density
      and vascular endothelial growth factor expression; EB1089 reverses these effects.
      Intracardially injected C4-2 cells produce predominantly osteoblastic lesions;
      PTHrP overexpression decreases the latency, increases the severity and alters the
      bone lesion profile to predominantly osteolytic. EB1089 largely reverses these
      PTHrP effects. A direct correlation between PTHrP immunoreactivity and increasing
      tumor grade is observed in human prostate cancer specimens. Thus, decreasing
      PTHrP production by treatment with vitamin D analogues may prove therapeutically
      beneficial for prostate cancer.

PMID- 19584237
TI  - Zalypsis (PM00104) is a potent inducer of gamma-H2AX foci and reveals the
      importance of the C ring of trabectedin for transcription-coupled repair
      inhibition.
AB  - Zalypsis (PM00104) is a novel tetrahydroisoquinoline alkaloid related to
      trabectedin [ecteinascidin 743 (Et743)]. Et743 and PM00104 have similar A and B
      rings but differ in their C rings. The present study shows that Et743 and PM00104
      differ in at least two ways: in their DNA binding properties and nucleotide
      excision repair (NER) dependency for cellular targeting. DNase I footprinting
      shows that the two drugs bind DNA differentially. We also found that, in contrast
      to Et743, the antiproliferative activity of PM00104 does not depend on
      transcription-coupled NER. Accordingly, PM00104 induces gamma-H2AX foci with the
      same efficiency in NER-deficient or NER-proficient cells. Moreover, the formation
      of gamma-H2AX foci is replication dependent for PM00104, whereas it is both
      transcription and replication dependent in the case of Et743. These findings show
      the importance of the C ring structure of tetrahydroisoquinoline ecteinascidin
      derivatives for NER targeting. Finally, PM00104 exerts antiproliferative activity
      at nanomolar concentrations and induces gamma-H2AX response in two Ewing's
      sarcoma cell lines, suggesting that gamma-H2AX could serve as a pharmacodynamic
      biomarker for the clinical development of PM00104.

PMID- 19584238
TI  - Upregulation of thrombospondin-1 and angiogenesis in an aggressive human
      pancreatic cancer cell line selected for high metastasis.
AB  - Pancreatic cancer remains a leading cause of death despite its relatively low
      incidence. As in many other solid tumors, angiogenesis is critical to the growth
      and metastasis of this cancer. Through serial in vivo passages in mice, we have
      developed a highly aggressive variant of human pancreatic cancer cell line XPA-1
      which shows more rapid primary tumor growth, faster time to metastasis, and more
      rapid lethality than the parental cell line. The high-metastatic variant
      developed a much denser tumor vasculature early during growth within the
      pancreas. Interestingly, examination of the in vitro growth of this aggressive
      variant yielded no significant difference from the parental cell line. Real-time
      PCR evaluation of genes involved in angiogenesis revealed a 24-fold increase in
      Thrombospondin-1 expression in cells derived from the high-metastatic variant
      when compared with the parental cell line. These findings provide direct evidence
      that elevated capability for angiogenesis, mediated by specific changes in gene
      expression, can lead to a large increase in cancer aggressiveness and resulting
      metastasis. These findings have important implications for the treatment of
      metastatic disease.

PMID- 19584239
TI  - Oncogenic transformation confers a selective susceptibility to the combined
      suppression of the proteasome and autophagy.
AB  - The proteasome and the autophagy systems are two evolutionarily conserved
      mechanisms for degrading intracellular materials. They are functionally coupled
      and suppression of the proteasome promotes autophagy. Although suppression of the
      proteasome leads to cell death, suppression of autophagy can be either prodeath
      or prosurvival. To understand the underlining mechanism of this dichotomy and its
      potential clinical implications, we treated various transformed and
      nontransformed human cells with proteasome inhibitors. We found that whether
      autophagy served a prosurvival role in this scenario was contingent on the
      cellular oncogenic status. Thus, autophagy suppression enhanced apoptosis induced
      by proteasome inhibitors in transformed cells, but not in nontransformed cells.
      Oncogenic transformation enhanced the ability of cells to initiate autophagy in
      response to stress, reflecting a stronger dependence of transformed cells on
      autophagy for survival. Indeed, a combined use of bortezomib, the only Food and
      Drug Administration-approved proteasome inhibitor for clinical use, and
      chloroquine, which inhibits autophagy by disturbing lysosomal functions,
      suppressed tumor growth more significantly than either agent alone in a xenograft
      model. These findings indicate that suppression of both intracellular degradation
      systems could constitute a novel strategy for enhanced cancer control in a tumor
      specific way.

PMID- 19584240
TI  - D,L-Sulforaphane causes transcriptional repression of androgen receptor in human
      prostate cancer cells.
AB  - D,L-Sulforaphane (SFN), a synthetic analogue of cruciferous vegetable-derived L
      isomer, inhibits the growth of human prostate cancer cells in culture and in vivo
      and retards cancer development in a transgenic mouse model of prostate cancer. We
      now show that SFN treatment causes transcriptional repression of androgen
      receptor (AR) in LNCaP and C4-2 human prostate cancer cells at pharmacologic
      concentrations. Exposure of LNCaP and C4-2 cells to SFN resulted in a
      concentration-dependent and time-dependent decrease in protein levels of total AR
      as well as Ser(210/213)-phosphorylated AR. The SFN-mediated decline in AR protein
      level was accompanied by a decrease in intracellular as well as secreted levels
      of prostate-specific antigen, an AR-regulated gene product. The decrease in AR
      protein level resulting from SFN exposure was not reversed in the presence of the
      protein synthesis inhibitor cycloheximide. Reverse transcription-PCR analysis
      revealed a dose-dependent decrease in AR mRNA levels, indicating transcriptional
      repression of this ligand-activated transcription factor. The SFN treatment
      inhibited AR promoter activity as revealed by luciferase reporter assay.
      Synthetic androgen (R1881)-stimulated nuclear translocation of AR was markedly
      suppressed in the presence of SFN in both cell lines. The SFN treatment also
      inhibited R1881-stimulated proliferation of LNCaP cells. Naturally occurring thio
      analogues (iberverin, erucin, and berteroin), but not the sulfonyl analogues
      (cheirolin, erysolin, and alyssin sulfone), of SFN were also effective in
      reducing protein levels of AR in LNCaP cells. In conclusion, the present study
      shows for the first time that SFN treatment causes transcriptional repression of
      AR and inhibition of its nuclear localization in human prostate cancer cells.

PMID- 19584241
TI  - Inhibition of S-adenosylmethionine decarboxylase by inhibitor SAM486A connects
      polyamine metabolism with p53-Mdm2-Akt/protein kinase B regulation and apoptosis
      in neuroblastoma.
AB  - S-adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme of polyamine
      (PA) biosynthesis, and both AdoMetDC and PA levels are often up-regulated in
      cancer cells. The second-generation inhibitor SAM486A inhibits AdoMetDC enzyme
      activity and has been evaluated in phase II clinical cancer trials. However,
      little is known about the mechanism of action and potential use of this
      therapeutic drug in the treatment of the pediatric cancer neuroblastoma (NB).
      Here, we show that p53 wild-type NB cells are highly sensitive to SAM486A
      treatment. Most notably, SAM486A treatment resulted in the rapid accumulation of
      proapoptotic proteins p53 and Mdm2. Concomitant with the increase of proteins at
      endogenous levels, the in vivo phosphorylation of p53 at residues
      Ser(46)/Ser(392) and Mdm2 at residue Ser(166) was observed. Moreover, the
      antiapoptotic protein Akt/protein kinase B was down-regulated and also
      dephosphorylated at residue Ser(473) in a dose- and time-dependent manner and NB
      cells entered apoptotic cell death. The results presented in this study highlight
      the importance of PA homeostasis and provide a direct link between PA metabolism
      and apoptotic cell signaling pathways in p53 wild-type NB cells. PA inhibitors
      such as SAM486A may be effective alternative agents for the treatment of NBs with
      or without MYCN amplification.

PMID- 19584243
TI  - Microbial methane oxidation processes and technologies for mitigation of landfill
      gas emissions.
AB  - Landfill gas containing methane is produced by anaerobic degradation of organic
      waste. Methane is a strong greenhouse gas and landfills are one of the major
      anthropogenic sources of atmospheric methane. Landfill methane may be oxidized by
      methanotrophic microorganisms in soils or waste materials utilizing oxygen that
      diffuses into the cover layer from the atmosphere. The methane oxidation process,
      which is governed by several environmental factors, can be exploited in
      engineered systems developed for methane emission mitigation. Mathematical models
      that account for methane oxidation can be used to predict methane emissions from
      landfills. Additional research and technology development is needed before
      methane mitigation technologies utilizing microbial methane oxidation processes
      can become commercially viable and widely deployed.

PMID- 19584242
TI  - Renal and liver tumors in Tsc2(+/-) mice, a model of tuberous sclerosis complex,
      do not respond to treatment with atorvastatin, a 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor.
AB  - Inactivating mutations of the tumor suppressor gene TSC2 are associated with
      tumorigenesis in tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis.
      Statins, as 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, have the
      potential to limit the growth of these tumors by limiting the isoprenylation of
      activated GTPases in Tsc2-null cells. We tested atorvastatin as a therapy for (a)
      ethylnitrosourea (ENU)-enhanced renal cystadenoma and (b) spontaneous liver
      hemangioma in 129Sv/Jae Tsc2(+/-) mice. ENU-treated Tsc2(+/-) mice were given
      atorvastatin chow (0.1%, w/w) for 1 or 3 months before sacrifice at 6 months;
      129Sv/Jae Tsc2(+/-) mice were given atorvastatin chow (0.1%, w/w) for 6 months
      before sacrifice at 12 months. All treatment groups were compared with mice of
      identical genotype and strain background that were fed control chow. Pathologic
      analyses revealed a predominance of renal cystadenoma in ENU-treated and liver
      hemangioma in non-ENU-treated 129Sv/Jae Tsc2(+/-) mice. In both cohorts, serum
      cholesterol levels and levels of phosphorylated S6 and GTP-RhoA in healthy tissue
      were significantly (>50%) reduced in atorvastatin-treated mice as compared with
      controls. Following atorvastatin treatment, no significant reduction in tumor
      size, morphology, or phosphorylated S6 levels was observed for either ENU
      associated renal cystadenoma or spontaneous liver hemangioma as compared with the
      untreated groups. In conclusion, although the marked reduction in cholesterol
      levels indicates that atorvastatin was effective as an 3-hydroxy-3-methylglutaryl
      CoA reductase inhibitor, it did not inhibit the growth of tumors that develop in
      these Tsc2(+/-) models, suggesting that it is unlikely to have benefit as a
      single-agent therapy for TSC-associated tumors.

PMID- 19584244
TI  - Experimental determination of upper bound for transition path times in protein
      folding from single-molecule photon-by-photon trajectories.
AB  - Transition paths are a uniquely single-molecule property not yet observed for any
      molecular process in solution. The duration of transition paths is the tiny
      fraction of the time in an equilibrium single-molecule trajectory when the
      process actually happens. Here, we report the determination of an upper bound for
      the transition path time for protein folding from photon-by-photon trajectories.
      FRET trajectories were measured on single molecules of the dye-labeled, 56
      residue 2-state protein GB1, immobilized on a glass surface via a biotin
      streptavidin-biotin linkage. Characterization of individual emitted photons by
      their wavelength, polarization, and absolute and relative time of arrival after
      picosecond excitation allowed the determination of distributions of FRET
      efficiencies, donor and acceptor lifetimes, steady state polarizations, and
      waiting times in the folded and unfolded states. Comparison with the results for
      freely diffusing molecules showed that immobilization has no detectable effect on
      the structure or dynamics of the unfolded protein and only a small effect on the
      folding/unfolding kinetics. Analysis of the photon-by-photon trajectories yields
      a transition path time <200 micros, >10,000 times shorter than the mean waiting
      time in the unfolded state (the inverse of the folding rate coefficient). Szabo's
      theory for diffusive transition paths shows that this upper bound for the
      transition path time is consistent with previous estimates of the Kramers
      preexponential factor for the rate coefficient, and predicts that the transition
      path time is remarkably insensitive to the folding rate, with only a 2-fold
      difference for rate coefficients that differ by 10(5)-fold.

PMID- 19584245
TI  - DNA-binding specificity and in vivo targets of Caenorhabditis elegans nuclear
      factor I.
AB  - The conserved nuclear factor I (NFI) family of transcription factors is unique to
      animals and essential for mammalian development. The Caenorhabditis elegans
      genome encodes a single NFI family member, whereas vertebrate genomes encode 4
      distinct NFI protein subtypes (A, B, C, and X). NFI-1-deficient worms exhibit
      abnormalities, including reduced lifespan, defects in movement and pharyngeal
      pumping, and delayed egg-laying. To explore the functional basis of these
      phenotypes, we sought to comprehensively identify NFI-1-bound loci in C. elegans.
      We first established NFI-1 DNA-binding specificity using an in vitro DNA
      selection strategy. Analysis yielded a consensus motif of TTGGCA(N)(3)TGCCAA,
      which occurs 586 times in the genome, a 100-fold higher frequency than expected.
      We next asked which sites were occupied by NFI-1 in vivo by performing chromatin
      immunoprecipitation of NFI-1 followed by microarray hybridization. Only 55
      genomic locations were identified, an unexpectedly small target set. In vivo NFI
      1 binding sites tend to be upstream of genes involved in core cellular processes,
      such as chromatin remodeling, mRNA splicing, and translation. Remarkably, 59 out
      of 70 (84%) of the C. briggsae orthologs of the identified targets contain
      conserved NFI binding sites in their promoters. These experiments provide a
      foundation for understanding how NFI-1 is recruited to unexpectedly few in vivo
      sites to perform its developmental functions, despite a vast over-representation
      of its binding motif.

PMID- 19584246
TI  - The virion-packaged endoribonuclease of herpes simplex virus 1 cleaves mRNA in
      polyribosomes.
AB  - The virion host shutoff protein product of the U(L)41 gene of herpes simplex
      virus 1 is an endoribonuclease that selectively degrades mRNAs during the first
      hours after infection. Specifically, in contrast to the events in uninfected
      cells or cells infected with a mutant lacking the RNase, in wild-type virus
      infected cells mRNA of housekeeping genes exemplified by GAPDH is degraded
      rapidly, whereas mRNAs containing AU elements are cleaved and the 5' cleavage
      product of these RNAs persists for many hours. We report that in wild-type virus
      infected cells there was a rapid increase in the number and size of processing
      bodies (P-bodies). These P-bodies were also preset in cycloheximide (CHX)-treated
      cells but not in either treated or untreated uninfected cells or cells infected
      with the RNase minus mutant. Additional studies revealed that polyribosomes
      extracted from cytoplasm of wild-type virus-infected cells treated with CHX and
      displayed in sucrose gradients contained ribosome-loaded, truncated AU-rich mRNAs
      lacking the 3' UTR and poly(A) tails. The results suggest that the virion RNase
      is bound to polyribosomes by virtue of the reported association with translation
      machinery and cleaves the RNAs 5' to the AU elements. In contrast to the slow
      degradation of the of the residual 5' domain, the 3' UTR of the AU-rich mRNA and
      the GAPDH mRNA are rapidly degraded in wild-type virus-infected cells.

PMID- 19584247
TI  - Direct electrophysiological measurement of human default network areas.
AB  - Neuroimaging-based investigations in humans have established the existence of
      brain regions that are selectively metabolically active while resting. We report
      a population-scale neurophysiological measurement of activity in regions of this
      "default network," by recording high-frequency power (76-200 Hz) electrical
      potentials directly from these regions in three human subjects. A selective
      increase observed during only resting, when compared with activity, firmly
      establishes a neuronal origin for default network phenomena.

PMID- 19584248
TI  - TRIMming p53 for ubiquitination.

PMID- 19584249
TI  - How can we learn efficiently to act optimally and flexibly?

PMID- 19584250
TI  - Dinuclear nickel complexes modeling the structure and function of the acetyl CoA
      synthase active site.
AB  - A dinuclear nickel complex with methyl and thiolate ligands,
      Ni(dadt(Et))Ni(Me)(SDmp) (2), has been synthesized as a dinuclear Ni(d)-Ni(p)
      site model of acetyl-CoA synthase (ACS) (dadt(Et) is N,N'-diethyl-3,7-diazanonane
      1,9-dithiolate; Dmp is 2,6-dimesitylphenyl). Complex 2 was prepared via 2
      methods: (i) ligand substitution of a dinuclear Ni(II)-Ni(II) cation complex
      [Ni(dadt(Et)) Ni(tmtu)2] (OTf)2 (1) with MeMgBr and KSDmp (tmtu is
      tetramethylthiourea), (ii) methyl transfer from methylcobaloxime
      Co(dmgBF2)2(Me)(Py) (5) to a Ni(II)-Ni(0) complex such as [Ni(dadt(Et))Ni(cod)]
      (3), generated in situ from Ni(dadt(Et)) and Ni(cod)(2), followed by addition of
      KSDmp (cod is 1,5-cyclooctadiene; dmgBF2 is difluoroboryl-dimethylglyoximate).
      Method ii models the formation of Nip-Me species proposed as a plausible
      intermediate in ACS catalysis. The reaction of 2 with excess CO affords the
      acetylthioester CH3C(O)SDmp (8) with concomitant formation of Ni(dadt(Et))Ni(CO)2
      (9) and Ni(CO)4 plus Ni(dadt(Et)). When complex 2 is treated with 1 equiv of CO
      in the presence of excess 1,5-cyclooctadiene, the formation of 9 and Ni(CO)4 is
      considerably suppressed, and instead the dinuclear Ni(II)-Ni(0) complex is
      generated in situ, which further affords 2 upon successive treatment with
      Co(dmgBF2)2(Me)(Py) (5) and KSDmp. These results suggest that (i) ACS catalysis
      could include the Nid(II)-Nip(0) state as the active species, (ii) The Nid(II)
      Nip(0) species could first react with methylcobalamin to afford Nid(II)-Nip(II)
      Me, and (iii) CO insertion into the Nip-Me bond and the successive reductive
      elimination of acetyl-CoA occurs immediately when CoA is coordinated to the Nip
      site to form the active Nid(II)-Nip(0) species.

PMID- 19584252
TI  - Genetic identification of putative remains of the famous astronomer Nicolaus
      Copernicus.
AB  - We report the results of mitochondrial and nuclear DNA analyses of skeletal
      remains exhumed in 2005 at Frombork Cathedral in Poland, that are thought to be
      those of Nicolaus Copernicus (1473-1543). The analyzed bone remains were found
      close to the altar Nicolaus Copernicus was responsible for during his tenure as
      priest. The mitochondrial DNA (mtDNA) profiles from 3 upper molars and the femurs
      were identical, suggesting that the remains originate from the same individual.
      Identical mtDNA profiles were also determined in 2 hairs discovered in a calendar
      now exhibited at Museum Gustavianum in Uppsala, Sweden. This calendar was the
      property of Nicolaus Copernicus for much of his life. These findings, together
      with anthropological data, support the identification of the human remains found
      in Frombork Cathedral as those of Nicolaus Copernicus. Up-to-now the particular
      mtDNA haplotype has been observed only 3 times in Germany and once in Denmark.
      Moreover, Y-chromosomal and autosomal short tandem repeat markers were analyzed
      in one of the tooth samples, that was much better preserved than other parts of
      the skeleton. Molecular sex determination revealed that the skeleton is from a
      male individual, and this result is consistent with morphological investigations.
      The minimal Y-chromosomal haplotype determined in the putative remains of
      Nicolaus Copernicus has been observed previously in many countries, including
      Austria, Germany, Poland, and the Czech Republic. Finally, an analysis of the SNP
      located in the HERC2 gene revealed the C/C genotype that is predominant in blue
      eyed humans, suggesting that Copernicus may have had a light iris color.

PMID- 19584251
TI  - Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic
      peptide mimics of Tat protein.
AB  - The interaction of the HIV-1 transactivator protein Tat with its transactivation
      response (TAR) RNA is an essential step in viral replication and therefore an
      attractive target for developing antivirals with new mechanisms of action.
      Numerous compounds that bind to the 3-nt bulge responsible for binding Tat have
      been identified in the past, but none of these molecules had sufficient potency
      to warrant pharmaceutical development. We have discovered conformationally
      constrained cyclic peptide mimetics of Tat that are specific nM inhibitors of the
      Tat-TAR interaction by using a structure-based approach. The lead peptides are
      nearly as active as the antiviral drug nevirapine against a variety of clinical
      isolates in human lymphocytes. The NMR structure of a peptide-RNA complex reveals
      that these molecules interfere with the recruitment to TAR of both Tat and the
      essential cellular cofactor transcription elongation factor-b (P-TEFb) by binding
      simultaneously at the RNA bulge and apical loop, forming an unusually deep
      pocket. This structure illustrates additional principles in RNA recognition: RNA
      binding molecules can achieve specificity by interacting simultaneously with
      multiple secondary structure elements and by inducing the formation of deep
      binding pockets in their targets. It also provides insight into the P-TEFb
      binding site and a rational basis for optimizing the promising antiviral activity
      observed for these cyclic peptides.

PMID- 19584254
TI  - Concerted proton-coupled electron transfers in aquo/hydroxo/oxo metal complexes:
      electrochemistry of [OsII(bpy)2py(OH2)]2+ in water.
AB  - Kinetic analysis of the successive oxidative cyclic voltammetric responses of
      [Os(II)(bpy)(2)py(OH(2))](2+) in buffered water, together with determination of
      H/D isotope effects, has allowed the determination of the mechanisms of the
      successive proton-coupled electron transfers that convert the Os(II)-aquo complex
      into the Os(III)-hydroxo complex and the later into the Os(IV)-oxo complex. The
      stepwise pathways prevail over the concerted pathway in the first case. However,
      very large concentrations of a base, such as acetate, trigger the beginning of a
      concerted reaction. The same trend appears, but to a much larger extent, when
      high local concentration of carboxylates are attached close to the Os complex.
      The Os(III)-hydroxo/Os(IV)-oxo couple is globally much slower and concerted
      pathways predominate over the stepwise pathways. Water is, however, not an
      appropriate proton acceptor in this respect. Other bases, such as citrate or
      phosphate, are instead quite effective for triggering concerted pathways. Here,
      we suggest factors causing these contrasting behaviors, providing a practical
      illustration of the prediction that concerted processes are an efficient way of
      avoiding high-energy intermediates. Observation of a strong decelerating effect
      of inactive ions together with the positive role of high local concentrations of
      carboxylates to initiate a concerted route underscores the variety of structural
      and medium factors that may operate to modulate and control the occurrence of
      concerted pathways. These demonstrations and analyses of the occurrence of
      concerted pathways in an aquo-hydroxo-oxo series are expected to serve as
      guidelines for studies in term of methodology and factor analysis.

PMID- 19584255
TI  - Overcoming systemic roadblocks to sustainable health.

PMID- 19584253
TI  - Long-term sensory deprivation selectively rearranges functional inhibitory
      circuits in mouse barrel cortex.
AB  - Long-term whisker removal alters the balance of excitation and inhibition in
      rodent barrel cortex, yet little is known about the contributions of individual
      cells and synapses in this process. We studied synaptic inhibition in four major
      types of neurons in live tangential slices that isolate layer 4 in the
      posteromedial barrel subfield. Voltage-clamp recordings of layer 4 neurons reveal
      that fast decay of synaptic inhibition requires alpha1-containing GABA(A)
      receptors. After 7 weeks of deprivation, we found that GABA(A)-receptor-mediated
      inhibitory postsynaptic currents (IPSCs) in the inhibitory low-threshold-spiking
      (LTS) cell recorded in deprived barrels exhibited faster decay kinetics and
      larger amplitudes in whisker-deprived barrels than those in nondeprived barrels
      in age-matched controls. This was not observed in other cell types. Additionally,
      IPSCs recorded in LTS cells from deprived barrels show a marked increase in
      zolpidem sensitivity. To determine if the faster IPSC decay in LTS cells from
      deprived barrels indicates an increase in alpha1 subunit functionality, we
      deprived alpha1(H101R) mutant mice with zolpidem-insensitive alpha1-containing
      GABA(A) receptors. In these mice and matched wild-type controls, IPSC decay
      kinetics in LTS cells were faster after whisker removal; however, the deprivation
      induced sensitivity to zolpidem was reduced in alpha1(H101R) mice. These data
      illustrate a change of synaptic inhibition in LTS cells via an increase in alpha1
      subunit-mediated function. Because alpha1 subunits are commonly associated with
      circuit-specific plasticity in sensory cortex, this switch in LTS cell synaptic
      inhibition may signal necessary circuit changes required for plastic adjustments
      in sensory-deprived cortex.

PMID- 19584256
TI  - Endometriosis: contribution of 3.0-T pelvic MR imaging in preoperative assessment
      -initial results.
AB  - PURPOSE: To determine the accuracy of 3.0-T pelvic magnetic resonance (MR)
      imaging in the preoperative assessment of endometriosis and to evaluate colon
      wall involvement after intrarectal gel administration. MATERIALS AND METHODS:
      Institutional review board approval for this study was obtained, and each patient
      gave written informed consent. Forty-one consecutive patients with clinical
      suspicion of endometriosis underwent pelvic MR imaging at 3.0 T before surgery.
      Single-shot and high-spatial-resolution axial T2-weighted, sagittal fat
      suppressed T2-weighted, and axial fat-suppressed T1-weighted sequences were
      performed. T2-weighted sequences were repeated after the rectum was filled with
      ultrasonographic (US) gel. Two blinded readers interpreted images independently.
      Image quality was scored by using a four-point scale. Detailed mapping of deep
      endometriosis was performed. Colon wall infiltration was graded (none, serosa,
      muscularis, submucosa, mucosa). MR imaging results were compared with surgical
      and pathologic findings. Interobserver agreement was assessed by using kappa
      statistics. Nonparametric tests were performed to compare colon wall infiltration
      scores without and those with US gel and between observers. RESULTS: Twenty-seven
      of 41 patients had deep endometriosis at surgery and histopathologic examination.
      Sensitivity, specificity, positive and negative predictive values, and accuracy
      for the diagnosis of deep endometriosis at MR imaging were 96.3% (26 of 27), 100%
      (14 of 14), 100% (26 of 26), 93.3% (14 of 15), and 97.6% (40 of 41),
      respectively. kappa Values ranged from 0.65 to 1.0, depending on the location of
      deep endometriosis. Colon wall infiltration assessment by both readers correlated
      well with pathologic findings (Spearman coefficient, >0.93), although median wall
      involvement scores were lower at pathologic examination than for both readers
      both before (P = .042 and P = .011) and after (P = .079 and P = .011) intrarectal
      gel filling. CONCLUSION: MR imaging of the pelvis at 3.0 T is accurate in the
      diagnosis and staging of deep endometriosis for the preoperative assessment of
      patients clinically suspected of having endometriosis.

PMID- 19584258
TI  - p21 expression is induced by activation of nuclear nerve growth factor-induced
      Balpha (Nur77) in pancreatic cancer cells.
AB  - 1,1-Bis(3'-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) activates the orphan
      receptor nerve growth factor-induced Balpha (Nur77) in cancer cells, and in this
      study, DIM-C-pPhOCH3 decreased Panc1 pancreatic cancer cell survival and arrested
      cells in G0-G1. These responses were accompanied by induction of the cyclin
      dependent kinase inhibitor p21 in pancreatic cancer cells. Mechanistic studies
      showed that induction of p21 mRNA and protein by DIM-C-pPhOCH3 was Nur77
      dependent but did not depend on Kruppel-like factor 4, which was also induced by
      DIM-C-pPhOCH3. Activation of p21 promoter constructs by DIM-C-pPhOCH3 required
      the GC-rich proximal region of the promoter, and results of RNA interference
      studies showed that Nur77-dependent activation of the p21 promoter involved
      interactions with Sp1 and Sp4 but not Sp3. Interactions of Nur77 with the p21
      promoter in Panc1 cells treated with DIM-C-pPhOCH3 were also confirmed in
      chromatin immunoprecipitation assays. These data show that activation of nuclear
      Nur77 results in a novel pathway for induction of p21, which is independent of
      Nur77 response elements but dependent on Sp proteins bound to the GC-rich
      proximal region of the p21 promoter.

PMID- 19584257
TI  - CXCR4 and matrix metalloproteinase-1 are elevated in breast carcinoma-associated
      fibroblasts and in normal mammary fibroblasts exposed to factors secreted by
      breast cancer cells.
AB  - The complex molecular communications that occur between neoplastic and stromal
      cells within the tumor microenvironment play an integral role in breast cancer
      pathogenesis. Carcinoma-associated fibroblasts (CAF) produce tumor-enhancing
      factors and have been strongly implicated in breast cancer development. Similar
      to the way in which tumors have been compared with "wounds that never heal," CAFs
      have been equated to activated fibroblasts, which are present in inflammatory
      environments, in which they aid in wound healing through tissue remodeling and
      repair. Matrix metalloproteinase-1 (MMP-1) and G protein-coupled receptor, CXCR4,
      are elevated in these activated fibroblasts, in which they facilitate
      angiogenesis and matrix degradation, processes that are also vital to breast
      cancer metastasis. In this study, we investigated MMP-1 and CXCR4 expression in
      normal human mammary fibroblasts (HMF) exposed to soluble breast cancer factors.
      Historically, elevated CXCR4 expression is associated with breast cancer cells.
      However, we show that soluble factors secreted by SUM102 breast cancer cells
      stimulated the expression of MMP-1 and CXCR4 in HMFs. As a result, these stromal
      cells acquired an invasive and migratory phenotype. To confirm the clinical
      relevancy of our findings, we analyzed CAFs obtained from primary breast cancers.
      These cells also displayed elevated MMP-1 and CXCR4 levels compared with
      counterpart fibroblasts, and were more invasive and migratory. Together, our data
      suggest that soluble breast cancer factors initiate the transdifferentiation of
      normal HMFs to tumor-promoting CAFs, and that through the induction of MMP-1 and
      CXCR4 levels, these cells exhibit an invasive and migratory phenotype.

PMID- 19584259
TI  - PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and
      BRCA2.
AB  - BRCA1 and BRCA2 are prominently associated with inherited breast and ovarian
      cancer. The encoded proteins function in DNA damage responses, but no functional
      link between BRCA1 and BRCA2 has been established. We show here that PALB2
      physically and functionally connects BRCA1 and BRCA2 into a DNA damage response
      network that also includes the RAD51 recombinase. PALB2 directly binds BRCA1, as
      determined with bacterially expressed fragments of each protein. Furthermore,
      PALB2 independently interacts with BRCA1 and BRCA2 through its NH2 and COOH
      termini, respectively. Critically, two point mutants (L21P and L24P) of the PALB2
      coiled-coil domain or an NH2-terminal deletion (Delta1-70) disrupt its
      interaction with BRCA1. We have reconstituted PALB2-deficient cells with
      PALB2Delta1-70, PALB2-L21P, or PALB2-L24P, or with COOH-terminally truncated
      PALB2 that is deficient for interaction with BRCA2. Using extracts from these
      cells, we find that PALB2 mediates the physical interaction of BRCA2 with a COOH
      terminal fragment of BRCA1. Analysis of the assembly of foci in these cells by
      BRCA1, PALB2, BRCA2, and RAD51 suggests that BRCA1 recruits PALB2, which in turn
      organizes BRCA2 and RAD51. Resistance to mitomycin C and the repair of DNA double
      strand breaks by homologous recombination require the interaction of PALB2 with
      both BRCA1 and BRCA2. These results suggest that BRCA1 and BRCA2 cooperate in DNA
      damage responses in a PALB2-dependent manner, and have important implications for
      the genesis of breast/ovarian cancer and for chemotherapy with DNA interstrand
      cross-linking agents.

PMID- 19584260
TI  - Therapeutic inhibition of the epidermal growth factor receptor in high-grade
      gliomas: where do we stand?
AB  - High-grade gliomas account for the majority of intra-axial brain tumors. Despite
      abundant therapeutic efforts, clinical outcome is still poor. Thus, new
      therapeutic approaches are intensely being investigated. Overexpression of the
      epidermal growth factor receptor (HER1/EGFR) is found in various epithelial
      tumors and represents one of the most common molecular abnormalities seen in high
      grade gliomas. Dysregulated HER1/EGFR is found in 40% to 50% of glioblastoma, the
      most malignant subtype of glioma. Several agents such as tyrosine kinase (TK)
      inhibitors, antibodies, radio-immuno conjugates, ligand-toxin conjugates, or RNA
      based agents have been developed to target HER1/EGFR or its mutant form,
      EGFRvIII. To date, most agents are in various stages of clinical development.
      Clinical data are sparse but most advanced for TK inhibitors. Although data from
      experimental studies seem promising, proof of a significant clinical benefit is
      still missing. Among the problems that have to be further addressed is the
      prediction of the individual patient's response to HER1/EGFR-targeted
      therapeutics based on molecular determinants. It is quite possible that blocking
      HER1/EGFR alone will not sufficiently translate into a clinical benefit.
      Therefore, a multiple target approach concomitantly aimed at different molecular
      sites might be a favorable concept. This review focuses on current HER1/EGFR
      targeted therapeutics and their development for high-grade gliomas.

PMID- 19584262
TI  - Cyclooxygenase-2 up-regulates ataxia telangiectasia and Rad3 related through
      extracellular signal-regulated kinase activation.
AB  - Cyclooxygenase-2 (COX-2) overexpression caused prolonged G2 arrest after exposure
      to ionizing radiation (IR) in our previous study. We were therefore interested in
      investigating the function of COX-2 in the G2 checkpoint pathway. Interestingly,
      we found that cells in which COX-2 is overexpressed showed up-regulated ataxia
      telangiectasia and Rad3 related (ATR) expression compared with control cells. In
      this study, we investigated the mechanism of ATR up-regulation by COX-2 and
      tested our hypothesis that COX-2-induced extracellular signal-regulated kinase
      (ERK) activation mediates up-regulation of ATR by COX-2. To investigate the
      relationship between COX-2 and ATR, we used two stable COX-2-overexpressing
      cancer cell lines (HCT116-COX-2 and H460-COX-2), a COX-2 knockdown A549 lung
      cancer cell line (AS), and an ATR knockdown HCT116 cell line. Cells were treated
      with various drugs [celecoxib, prostaglandin E2 (PGE2), PD98059, U0126, and
      hydroxyurea] and were then analyzed using reverse transcription-PCR, confocal
      microscopy, Western blotting, and clonogenic assay. COX-2-overexpressing cells
      were shown to have increased ERK phosphorylation and ATR expression compared with
      control cells, whereas AS cells were shown to have decreased levels of phospho
      ERK and ATR. In addition, exogenously administered PGE2 increased ERK
      phosphorylation. Inhibition of ERK phosphorylation decreased ATR expression in
      both HCT116-COX-2 and A549 cells. HCT116-COX-2 cells were resistant to IR or
      hydroxyurea compared with HCT116-Mock cells, whereas administration of ATR shRNA
      showed the opposite effect. COX-2 stimulates ERK phosphorylation via PGE2. This
      COX-2-induced ERK activation seems to increase ATR expression and activity in
      endogenous COX-2-overexpressing cancer cells as well as in COX-2-overexpressing
      stable cell lines.

PMID- 19584261
TI  - Requirement of phosphatidylinositol(3,4,5)trisphosphate in phosphatidylinositol 3
      kinase-induced oncogenic transformation.
AB  - Phosphatidylinositol 3-kinases (PI3K) are divided into three classes, which
      differ in their substrates and products. Class I generates the inositol
      phospholipids PI(3)P, PI(3,4)P2, and PI(3,4,5)P3 referred as PIP, PIP2, and PIP3,
      respectively. Class II produces PIP and PIP2, and class III generates only PIP.
      Substrate and product differences of the three classes are determined by the
      activation loops of their catalytic domains. Substitution of the class I
      activation loop with either class II or III activation loop results in a
      corresponding change of substrate preference and product restriction. We have
      evaluated such activation loop substitutions to show that oncogenic activity of
      class I PI3K is linked to the ability to produce PIP3. We further show that
      reduction of cellular PIP3 levels by the 5'-phosphatase PIPP interferes with PI3K
      induced oncogenic transformation. PIPP also attenuates signaling through Akt and
      target of rapamycin. Class III PI3K fails to induce oncogenic transformation.
      Likewise, a constitutively membrane-bound class I PI3K mutant retaining only the
      protein kinase is unable to induce transformation. We conclude that PIP3 is an
      essential component of PI3K-mediated oncogenesis and that inability to generate
      PIP3 abolishes oncogenic potential.

PMID- 19584263
TI  - Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma
      deficient cells to DNA damage-induced necrosis.
AB  - The retinoblastoma (Rb) tumor suppressor is a key regulator of cell cycle
      checkpoints but also protects against cell death induced by stresses such as DNA
      damage and death receptor ligation. We report here that cell death of Rb
      deficient cells exposed to key genotoxic agents was associated with increased
      expression of S phase-specific E2F target genes and cell death consistently
      occurred in the S phase of the cell cycle. Cell cycle arrest induced by serum
      starvation prevented S phase entry, attenuated DNA damage, and promoted survival,
      suggesting that Rb-null cells die due to a failure to prevent S phase entry. DNA
      damage-induced death of Rb-null cells was associated with nucleotide depletion,
      higher activity of poly-ADP-ribose-polymerase (Parp), and cell death that was
      primarily necrotic. Knockdown of Parp-1 or chemical inhibition of Parp activity
      prevented nucleotide depletion and restored the viability of Rb-deficient cells
      to wild-type levels. Furthermore, chemical inhibition of Parp activity in vivo
      attenuated the cytotoxic effects of cisplatin against Rb-deficient tumors,
      arguing that Parp inhibitors should not be used therapeutically in combination
      with genotoxic drugs against tumors that are inactivated for the Rb tumor
      suppressor.

PMID- 19584264
TI  - Nuclear factor-kappaB inhibition by parthenolide potentiates the efficacy of
      Taxol in non-small cell lung cancer in vitro and in vivo.
AB  - In this study, we have examined the molecular events induced by parthenolide, a
      sesquiterpene lactone, and explored possible mechanisms of resistance and
      sensitization of tumor cells to Taxol. We showed that parthenolide could
      antagonize Taxol-mediated nuclear factor-kappaB (NF-kappaB) nuclear translocation
      and activation and Bcl-xl up-regulation by selectively targeting I-kappaB kinase
      activity. In A549 cells, inhibition of nuclear factor-kappaB by parthenolide
      resulted in activation of the mitochondrial death pathway to promote cytochrome c
      release and caspase 3 and 9 activation. In contrast, Taxol alone induced
      apoptosis via a pathway independent of mitochondria cytochrome c cascade. In
      addition, depletion of Bcl-xl rescued the apoptotic response to Taxol. Moreover,
      treatment with parthenolide increased the efficacy of the Taxol-induced
      inhibition of A549 tumor xenografts in mice. This study elucidated the cellular
      responses induced by parthenolide that decrease the threshold of mitochondria
      dependent apoptosis in the treatment of non-small cell lung cancer cells.

PMID- 19584265
TI  - Matrix protein CCN1 is critical for prostate carcinoma cell proliferation and
      TRAIL-induced apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an
      important role in immune surveillance and preferentially induces apoptosis in
      cancer cells over normal cells, suggesting its potential in cancer therapy.
      However, the molecular basis for its selective killing of cancer cells is not
      well understood. Recent studies have identified the CCN family of integrin
      binding matricellular proteins as important regulators of cell behavior,
      including cell adhesion, proliferation, migration, differentiation, and survival.
      We show here that CCN1 (CYR61) supports the adhesion of prostatic carcinoma cells
      as an adhesion substrate through integrins and heparan sulfate proteoglycans.
      Knockdown of CCN1 expression in PC-3 and DU-145 androgen-independent prostate
      cancer cells strongly inhibited their proliferation without causing apoptosis,
      indicating that CCN1 promotes their growth. However, CCN1 also significantly
      enhances TRAIL-induced apoptosis through interaction with integrins alphavbeta3
      and alpha6beta4 and the cell-surface heparan sulfate proteoglycan syndecan-4,
      acting through a protein kinase Calpha-dependent mechanism without requiring de
      novo protein synthesis. Knockdown of CCN1 expression in PC-3, DU-145, and LNCaP
      cells severely blunted their sensitivity to TRAIL, an effect that was reversed by
      exogenously added CCN1 protein. These findings reveal a functional dichotomy for
      CCN1 in prostate carcinoma cells, because it contributes to both cell
      proliferation and TRAIL-induced cell death and suggest that CCN1 expression
      status may be an important parameter in assessing the efficacy of TRAIL-dependent
      cancer therapy.

PMID- 19584266
TI  - Targeting of tumor blood vessels: a phage-displayed tumor-homing peptide
      specifically binds to matrix metalloproteinase-2-processed collagen IV and blocks
      angiogenesis in vivo.
AB  - Proteolytic degradation of the basement membrane by the matrix metalloproteinase
      2 and -9 is an essential step in tumor angiogenesis. On proteolytic degradation,
      cryptic sites in collagen IV are formed, which serve as a migration signal for
      endothelial cells and are specific for angiogenic blood vessels. The aim of this
      study was to generate peptides that bind specifically to proteolytically
      processed collagen IV and to test whether these peptides accumulate in tumor
      vasculature and are able to block angiogenesis. To obtain such peptides, we
      performed a combined in vivo and in vitro phage display screen using a
      recombinant phage-displayed peptide library. We found a phage displaying the
      peptide sequence TLTYTWS that specifically binds to collagen IV modified by
      matrix metalloproteinase-2. We then tested the ability of the phage to bind to
      the vasculature in xenograft tumors and found indeed a significant accumulation
      of the phage in tumors but not in control organs. The tumor homing of the TLTYTWS
      phage is specific, as it can be blocked by coinjection chemically synthesized
      cognate peptide. Moreover, TLTYTWS peptide inhibits angiogenesis in an in vivo
      assay in a concentration-dependent manner and significantly reduces endothelial
      differentiation in vitro. In conclusion, we report about a novel tumor-homing
      peptide that specifically binds to proteolytically processed collagen IV,
      accumulates in tumors, and blocks angiogenesis. This peptide may be a new useful
      tool for diagnostic and therapeutic procedures in oncology.

PMID- 19584268
TI  - Platelets: guardians of tumor vasculature.
AB  - Solid tumors generate a prothrombotic environment capable of platelet activation.
      Recent findings indicate that the activated platelets are crucial regulators of
      tumor vascular homeostasis in that they prevent tumor hemorrhage. Surprisingly,
      this effect is independent of platelets' capacity to form thrombi and instead
      relies on the secretion of their granule content. Thus, targeting platelet
      secretory activities may represent a new approach to specifically destabilize
      tumor vasculature.

PMID- 19584267
TI  - Parathyroid hormone-related protein regulates cell survival pathways via integrin
      alpha6beta4-mediated activation of phosphatidylinositol 3-kinase/Akt signaling.
AB  - Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic
      tissues and cancer cell lines. PTHrP enhances tumor cell growth and metastasis in
      vivo and up-regulates proinvasive integrin alpha6beta4 expression in vitro.
      Hallmarks of malignant tumor cells include resistance to apoptosis and anchorage
      independent cell growth. In this study, we used the human prostate cancer cell
      lines C4-2 and PC-3 as model systems to study the effects of PTHrP on these
      processes. We report that PTHrP protects these cells from doxorubicin-induced
      apoptosis and promotes anchorage-independent cell growth via an intracrine
      pathway. Conversely, autocrine/paracrine PTHrP action increases apoptosis in C4-2
      cells and has no effect on apoptosis in PC-3 cells. The intracrine effects of
      PTHrP on apoptosis are mediated via activation of the phosphatidylinositol 3
      kinase (PI3K)/Akt pathway. PTHrP also affects the phosphorylation state of Akt
      substrates implicated in apoptosis suppression, including glycogen synthase
      kinase-3 and Bad. The prosurvival effects of PTHrP are accompanied by increases
      in the ratio of antiapoptotic to proapoptotic members of the Bcl-2 family and in
      levels of c-myc. PTHrP also increases nuclear factor-kappaB activity via a PI3K
      dependent pathway. Integrin alpha6beta4 is known to activate PI3K. Here, we also
      show that knockdown of integrin alpha6beta4 negates the PTHrP-mediated activation
      of the PI3K/Akt pathway. Taken together, these observations provide evidence of a
      link between PTHrP and the PI3K/Akt signaling pathway through integrin
      alpha6beta4, resulting in the activation of survival pathways. Targeting PTHrP
      production in prostate cancer may thus prove therapeutically beneficial.

PMID- 19584269
TI  - MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and
      regulates its functions.
AB  - MicroRNAs (miR) have been identified as posttranscriptional modifiers of target
      gene regulation and control the expression of gene products important in cancer
      progression. Here, we show that miR-661 inhibits the expression of metastatic
      tumor antigen 1 (MTA1), a widely up-regulated gene product in human cancer, by
      targeting the 3' untranslated region (UTR) of MTA1 mRNA. We found that endogenous
      miR-661 expression was positively regulated by the c/EBPalpha transcription
      factor, which is down-regulated during cancer progression. c/EBPalpha directly
      interacted with the miR-661 chromatin and bound to miR-661 putative promoter that
      contains a c/EBPalpha-consensus motif. In addition, we found that the level of
      MTA1 protein was progressively up-regulated, whereas that of miR-661 and its
      activator, c/EBPalpha, were down-regulated in a breast cancer progression model
      consisting of MCF-10A cell lines whose phenotypes ranged from noninvasive to
      highly invasive. c/EBPalpha expression in breast cancer cells resulted in
      increased miR-661 expression and reduced MTA1 3'UTR-luciferase activity and MTA1
      protein level. We also provide evidence that the introduction of miR-661
      inhibited the motility, invasiveness, anchorage-independent growth, and
      tumorigenicity of invasive breast cancer cells. We believe our findings show for
      the first time that c/EBPalpha regulates the level of miR-661 and in turn
      modifies the functions of the miR661-MTA1 pathway in human cancer cells. Based on
      these findings, we suggest that miR-661 be further investigated for therapeutic
      use in down-regulating the expression of MTA1 in cancer cells.

PMID- 19584271
TI  - The emerging role of EpCAM in cancer and stem cell signaling.
AB  - Initially discovered as a dominant antigen on colon carcinomas, the epithelial
      cell adhesion molecule (EpCAM) was considered a mere cell adhesion molecule and
      reliable surface-binding site for therapeutic antibodies. Recent findings can
      better explain the relevance of EpCAM's high-level expression on human cancers
      and cancer propagating cells, and its negative prognostic potential for survival
      of patients with certain cancers. EpCAM has oncogenic potential and is activated
      by release of its intracellular domain, which can signal into the cell nucleus by
      engagement of elements of the wnt pathway.

PMID- 19584270
TI  - Activating transcription factor 2 and c-Jun-mediated induction of FoxP3 for
      experimental therapy of mammary tumor in the mouse.
AB  - FOXP3 is inactivated in breast cancer cells by a number of mechanisms, including
      somatic mutations, deletion, and epigenetic silencing. Because the mutation and
      deletion are usually heterozygous in the cancer samples, it is of interest to
      determine whether the gene can be induced for the purpose of cancer therapy.
      Here, we report that anisomycin, a potent activator of activating transcription
      factor (ATF) 2, and c-Jun-NH(2)-kinase, induces expression of FoxP3 in both
      normal and malignant mammary epithelial cells. The induction is mediated by ATF2
      and c-Jun. Targeted mutation of ATF2 abrogates both constitutive and inducible
      expression of FoxP3 in normal epithelial cells. Both ATF2 and c-Jun interact with
      a novel enhancer in the intron 1 of the FoxP3 locus. Moreover, shRNA silencing of
      ATF2 and FoxP3 reveals an important role of ATF2-FoxP3 pathway in the anisomycin
      induced apoptosis of breast cancer cells. A low dose of anisomycin was also
      remarkably effective in treating established mammary tumor in the mice. Our data
      showed that FoxP3 can be reactivated for cancer therapy.

PMID- 19584273
TI  - MicroRNA classifiers for predicting prognosis of squamous cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC), which is comprised mainly of adenocarcinoma
      and squamous cell carcinoma (SCC), is the cause of 80% of all lung cancer deaths
      in the United States. NSCLC is also associated with a high rate of relapse after
      clinical treatment and, therefore, requires robust prognostic markers to better
      manage therapy options. The aim of this study was to identify microRNA (miRNA)
      expression profiles in SCC of the lung that would better predict prognosis. Total
      RNA from 61 SCC samples and 10 matched normal lung samples was processed for
      small RNA species and profiled on MirVana miRNA Bioarrays (version 2, Ambion). We
      identified 15 miRNAs that were differentially expressed between normal lung and
      SCC, including members of the miR-17-92 cluster and its paralogues. We also
      identified miRNAs, including miR-155 and let-7, which had previously been shown
      to have prognostic value in adenocarcinoma. Based on cross-fold validation
      analyses, miR-146b alone was found to have the strongest prediction accuracy for
      stratifying prognostic groups at approximately 78%. The miRNA signatures were
      superior in predicting overall survival than a previously described 50-gene
      prognostic signature. Whereas there was no overlap between the mRNAs targeted by
      the prognostic miRNAs and the 50-gene expression signature, there was a
      significant overlap in the corresponding biological pathways, including
      fibroblast growth factor and interleukin-6 signaling. Our data indicate that
      miRNAs may have greater clinical utility in predicting the prognosis of patients
      with squamous cell lung carcinomas than mRNA-based signatures.

PMID- 19584274
TI  - Tumor necrosis factor-alpha and interleukin-1 antagonists alleviate inflammatory
      skin changes associated with epidermal growth factor receptor antibody therapy in
      mice.
AB  - Cancer patients receiving epidermal growth factor receptor (EGFR) antibody
      therapy often experience an acneiform rash of uncertain etiology in skin regions
      rich in pilosebaceous units. Currently, this condition is treated symptomatically
      with very limited, often anecdotal success. Here, we show that a monoclonal
      antibody targeting murine EGFR, ME1, caused a neutrophil-rich hair follicle
      inflammation in mice, similar to that reported in patients. This effect was
      preceded by the appearance of lipid-filled hair follicle distensions adjacent to
      enlarged sebaceous glands. The cytokine tumor necrosis factor-alpha (TNFalpha),
      localized immunohistochemically to this affected region of the pilosebaceous
      unit, was specifically up-regulated by ME1 in skin but not in other tissues
      examined. Moreover, skin inflammation was reduced by cotreatment with the
      TNFalpha signaling inhibitor, etanercept, indicating the involvement of TNFalpha
      in this inflammatory process. Interleukin-1, a cytokine that frequently acts in
      concert with TNFalpha, is also involved in this process given the efficacy of the
      interleukin-1 antagonist Kineret. Our results provide a mechanistic framework to
      develop evidence-based trials for EGFR antibody-induced skin rash in patients
      with cancer.

PMID- 19584272
TI  - Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter
      cohort of BRCA1/2 mutation carriers.
AB  - Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of
      factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation
      carriers is important because no effective early detection for ovarian cancers
      exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to
      evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and
      TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed
      with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was
      observed for one haplotype with a multiple testing corrected P (P(corr)) = 0.012,
      although no individual haplotype was significant. At MRE11, statistically
      significant associations were observed for one haplotype (P(corr) = 0.007). At
      NBS1, we observed a P(corr) = 0.024 for haplotypes. In BRCA2 carriers, no
      associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at
      ATM (P(corr) = 0.044) and BARD1 (P(corr) = 0.012) were associated with ovarian
      cancer risk. At BRIP1, two common haplotypes were significantly associated with
      ovarian cancer risk (P(corr) = 0.011). At MRE11, we observed a significant
      haplotype association (P(corr) = 0.012), and at RAD51, one common haplotype was
      significantly associated with ovarian cancer risk (P(corr) = 0.026). Variants in
      genes that interact biologically withBRCA1 and/or BRCA2 may be associated with
      modified ovarian cancer risk in women who carry BRCA1/2 mutations.

PMID- 19584275
TI  - Epstein-Barr virus latent membrane protein-1 effects on junctional plakoglobin
      and induction of a cadherin switch.
AB  - Latent membrane protein-1 (LMP1) is considered the major oncoprotein of Epstein
      Barr virus and is frequently expressed in nasopharyngeal carcinoma (NPC). LMP1
      promotes growth and migration of epithelial cells, and the loss of plakoglobin
      has been identified as a contributing factor to LMP1-induced migration.
      Plakoglobin is a junctional protein that can also serve as a transcription factor
      in Tcf/Lef signaling. To determine the effects of LMP1 on the molecular and
      functional properties of plakoglobin, LMP1 was overexpressed in the NPC cell line
      C666-1. LMP1 did not affect plakoglobin stability but did decrease plakoglobin
      transcription. The resultant decreased levels of nuclear plakoglobin did not
      affect Tcf/Lef activity or the amount of plakoglobin bound to Tcf4. Although LMP1
      induced and stabilized beta-catenin, a protein with common binding partners to
      plakoglobin, the loss of plakoglobin did not affect its association with Tcf4.
      However, LMP1 did induce a cadherin switch from E- to N-cadherin, a process
      involved in cancer progression, and enhanced the association of junctional beta
      catenin with N-cadherin. LMP1 decreased overall levels of junctional plakoglobin
      but the remaining junctional plakoglobin was found associated with the induced N
      cadherin. This increased association of junctional plakoglobin with N-cadherin
      was a distinguishing feature of LMP1-expressing cells that have reduced migration
      due to restoration of plakoglobin. Low levels of plakoglobin were also detected
      in human NPC tissues. These findings reveal that the effects of LMP1 on
      junctional plakoglobin and the initiation of a cadherin switch likely contribute
      to metastasis of NPC.

PMID- 19584277
TI  - Cytogenetic and cDNA microarray expression analysis of MCF10 human breast cancer
      progression cell lines.
AB  - We used a combination of spectral karyotyping, array comparative genomic
      hybridization, and cDNA microarrays to gain insights into the structural and
      functional changes of the genome in the MCF10 human breast cancer progression
      model cell lines. Spectral karyotyping data showed several chromosomal
      aberrations and array comparative genomic hybridization analysis identified
      numerous genomic gains and losses that might be involved in the progression
      toward cancer. Analysis of the expression levels of genes located within these
      genomic regions revealed a lack of correlation between chromosomal gains and
      losses and corresponding up-regulation or down-regulation for the majority of the
      approximately 1,000 genes analyzed in this study. We conclude that other
      mechanisms of gene regulation that are not directly related to chromosomal gains
      and losses play a major role in breast cancer progression.

PMID- 19584276
TI  - Long-lived Min mice develop advanced intestinal cancers through a genetically
      conservative pathway.
AB  - C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop
      numerous adenomas along the entire length of the intestine and consequently die
      at an early age. This short lifespan would prevent the accumulation of somatic
      genetic mutations or epigenetic alterations necessary for tumor progression. To
      overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing
      C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids
      developed few intestinal tumors and often lived longer than 1 year. Many of the
      tumors (24-87%) were invasive adenocarcinomas, in which neoplastic tissue
      penetrated through the muscle wall into the mesentery. In a few cases (3%),
      lesions metastasized by extension to regional lymph nodes. The development of
      these familial cancers does not require chromosomal gains or losses, a high level
      of microsatellite instability, or the presence of Helicobacter. To test whether
      genetic instability might accelerate tumor progression, we generated Apc(Min/+)
      mice homozygous for the hypomorphic allele of the Nijmegen breakage syndrome gene
      (Nbs1(DeltaB)) and also treated Apc(Min/+) mice with a strong somatic mutagen.
      These imposed genetic instabilities did not reduce the time required for cancers
      to form nor increase the percentage of cancers nor drive progression to the point
      of distant metastasis. In summary, we have found that the Apc(Min/+) mouse model
      for familial intestinal cancer can develop frequent invasive cancers in the
      absence of overt genomic instability. Possible factors that promote invasion
      include age-dependent epigenetic changes, conservative somatic recombination, or
      direct effects of alleles in the F(1) hybrid genetic background.

PMID- 19584278
TI  - Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase
      7 expression.
AB  - The high mortality rate of lung cancer is largely due to the spread of disease to
      other organs. However, the molecular changes driving lung cancer invasion and
      metastasis remain unclear. In this study, we identified fibulin-5, a vascular
      ligand for integrin receptors, as a suppressor of lung cancer invasion and
      metastasis. Fibulin-5 was silenced by promoter hypermethylation in a majority of
      lung cancer cell lines and primary tumors. It inhibited lung cancer cell invasion
      and down-regulated matrix metalloproteinase-7 (MMP-7), which promoted lung cancer
      cell invasion. Knockdown of fibulin-5 was sufficient to stimulate cell invasion
      and MMP-7 expression. The expression levels of fibulin-5 and MMP-7 were inversely
      correlated in lung tumors. Suppression of MMP-7 expression by fibulin-5 was
      mediated by an integrin-binding RGD motif via the extracellular signal-regulated
      kinase (ERK) pathway. Furthermore, overexpression of fibulin-5 in H460 lung
      cancer cells inhibited metastasis in mice. Collectively, these results suggest
      that epigenetic silencing of fibulin-5 promotes lung cancer invasion and
      metastasis by activating MMP-7 expression through the ERK pathway.

PMID- 19584279
TI  - Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in
      castration-resistant prostate cancer.
AB  - It seems clear that androgen receptor (AR)-regulated expression of the
      TMPRSS2:ERG fusion gene plays an early role in prostate cancer (PC) development
      or progression, but the extent to which TMPRSS2:ERG is down-regulated in response
      to androgen deprivation therapy (ADT) and whether AR reactivates TMPRSS2:ERG
      expression in castration-resistant PC (CRPC) have not been determined. We show
      that ERG message levels in TMPRSS2:ERG fusion-positive CRPC are comparable with
      the levels in fusion gene-positive primary PC, consistent with the conclusion
      that the TMPRSS2:ERG expression is reactivated by AR in CRPC. To further assess
      whether TMPRSS2:ERG expression is initially down-regulated in response to ADT, we
      examined VCaP cells, which express the TMPRSS2:ERG fusion gene, and xenografts.
      ERG message and protein rapidly declined in response to removal of androgen in
      vitro and castration in vivo. Moreover, as observed in the clinical samples, ERG
      expression was fully restored in the VCaP xenografts that relapsed after
      castration, coincident with AR reactivation. AR reactivation in the relapsed
      xenografts was also associated with marked increases in mRNA encoding AR and
      androgen synthetic enzymes. These results show that expression of TMPRSS2:ERG,
      similarly to other AR-regulated genes, is restored in CRPC and may contribute to
      tumor progression.

PMID- 19584280
TI  - Biochemical, cellular, and in vivo activity of novel ATP-competitive and
      selective inhibitors of the mammalian target of rapamycin.
AB  - The mammalian target of rapamycin (mTOR) is centrally involved in cell growth,
      metabolism, and angiogenesis. While showing clinical efficacy in a subset of
      tumors, rapamycin and rapalogs are specific and allosteric inhibitors of mTOR
      complex 1 (mTORC1), but they do not directly inhibit mTOR complex 2 (mTORC2), an
      emerging player in cancer. Here, we report chemical structure and biological
      characterization of three pyrazolopyrimidine ATP-competitive mTOR inhibitors, WAY
      600, WYE-687, and WYE-354 (IC(50), 5-9 nmol/L), with significant selectivity over
      phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold). Unlike the rapalogs,
      these inhibitors acutely blocked substrate phosphorylation by mTORC1 and mTORC2
      in vitro and in cells in response to growth factor, amino acids, and hyperactive
      PI3K/AKT. Unlike the inhibitors of PI3K or dual-pan PI3K/mTOR, cellular
      inhibition of P-S6K1(T389) and P-AKT(S473) by the pyrazolopyrimidines occurred at
      significantly lower inhibitor concentrations than those of P-AKT(T308) (PI3K-PDK1
      readout), showing mTOR selectivity in cellular setting. mTOR kinase inhibitors
      reduced AKT downstream function and inhibited proliferation of diverse cancer
      cell lines. These effects correlated with a strong G(1) cell cycle arrest in both
      the rapamycin-sensitive and rapamycin-resistant cells, selective induction of
      apoptosis, repression of global protein synthesis, and down-regulation of
      angiogenic factors. When injected into tumor-bearing mice, WYE-354 inhibited
      mTORC1 and mTORC2 and displayed robust antitumor activity in PTEN-null tumors.
      Together, our results highlight mechanistic differentiation between rapalogs and
      mTOR kinase inhibitors in targeting cancer cell growth and survival and provide
      support for clinical development of mTOR kinase inhibitors as new cancer therapy.

PMID- 19584281
TI  - Positive feedback activation of estrogen receptors by the CXCL12-CXCR4 pathway.
AB  - Induction of estrogen-regulated gene transcription by estrogen receptors ERalpha
      and ERbeta plays an important role in breast cancer development and growth. High
      expression of the chemokine receptor CXCR4 and its ligand CXCL12/stromal cell
      derived factor 1 (SDF-1) has also been correlated with aggressive breast tumor
      phenotypes. Here, we describe a positive regulatory loop between the CXCR4/SDF-1
      signaling pathway and ER transcriptional competence in human breast cancer cells.
      Treatment of breast carcinoma MCF-7 cells with SDF-1 increased ER transcriptional
      activity and expression of ER target genes, including SDF-1 itself. These effects
      were blocked by the antiestrogen ICI-182780 and by CXCR4 silencing and,
      conversely, estrogen-induced gene expression and growth of MCF-7 cells were
      impaired on CXCR4 inhibition. Both ERalpha and ERbeta were activated by SDF-1 in
      the presence of CXCR4 and by overexpression of a constitutively active CXCR4,
      indicating that CXCR4 signals to both receptors. In particular, ERbeta was able
      to translate the effects of SDF-1 on its own expression, as well as enhance
      activator protein 1 (AP-1) containing genes cyclin D1 and c-Myc in the presence
      of tamoxifen. This correlated with an increased ERbeta occupancy of responsive
      promoters at both estrogen-responsive and AP-1 elements. Ser-87, a conserved
      mitogen-activated protein kinase site in ERbeta, was highly phosphorylated by SDF
      1, revealing an essential role of the AF-1 domain in response to CXCR4
      activation. These results identify a complete autocrine loop between the
      CXCR4/SDF-1 and ERalpha/ERbeta signaling pathways that dictates ER-dependent gene
      expression and growth of breast cancer cells.

PMID- 19584282
TI  - High efficacy of a Listeria-based vaccine against metastatic breast cancer
      reveals a dual mode of action.
AB  - Most cancer vaccines induce CTL responses to tumor-associated antigens (TAA).
      Killing of tumor cells occurs through TAA-specific CTL-mediated cytolysis. Here,
      we show that one preventive followed by two therapeutic immunizations with an
      attenuated Listeria monocytogenes (LM)-based vaccine eradicates all metastases
      and almost the entire primary tumor in the syngeneic, aggressive mouse breast
      tumor model 4T1. We provide strong evidence that this is due to the combined
      result of direct kill by Listeria infecting the tumor cells and by CTL responses
      against Listeria antigens. We showed by electron microscopy that LM expressing
      truncated listeriolysin O (LLO) and amino acid fragments 311 to 660 of TAA Mage-b
      (LM-LLO-Mage-b(311-660)) and the control strain LM-LLO infect tumor cells in
      vitro and in vivo. In vitro data indicate that tumor cell death occurs through
      activation of NADP(+) oxidase and increased intracellular Ca(2+) levels, both
      resulting in the production of high ROS levels. Because both LM-LLO and LM-LLO
      Mage-b(311-660) showed equally strong efficacies in vivo, we concluded that LM
      LLO was crucial and Mage-b was of less importance. We found strong CTL responses
      to LM-LLO in the spleen, and depletion of CD8 T cells in vivo resulted in
      significant tumor regrowth (52%) in LM-LLO-vaccinated mice, indicating that LM
      LLO-specific CTL indeed partially contributed to tumor cell kill in vivo. This
      dual mode of action of a Listeria-based vaccine has not been described before and
      may provide new directions in the development of more effective vaccines against
      metastatic breast cancer.

PMID- 19584283
TI  - MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin
      sensitivity of human hepatocarcinoma cells.
AB  - The identification of target genes is a key step for assessing the role of
      aberrantly expressed microRNAs (miRNA) in human cancer and for the further
      development of miRNA-based gene therapy. MiR-122 is a liver-specific miRNA
      accounting for 70% of the total miRNA population. Its down-regulation is a common
      feature of both human and mouse hepatocellular carcinoma (HCC). We have
      previously shown that miR-122 can regulate the expression of cyclin G1, whose
      high levels have been reported in several human cancers. We evaluated the role of
      miR-122 and cyclin G1 expression in hepatocarcinogenesis and in response to
      treatment with doxorubicin and their relevance on survival and time to recurrence
      (TTR) of HCC patients. We proved that, by modulating cyclin G1, miR-122
      influences p53 protein stability and transcriptional activity and reduces
      invasion capability of HCC-derived cell lines. In addition, in a therapeutic
      perspective, we assayed the effects of a restored miR-122 expression in
      triggering doxorubicin-induced apoptosis and we proved that miR-122, as well as
      cyclin G1 silencing, increases sensitivity to doxorubicin challenge. In patients
      resected for HCC, lower miR-122 levels were associated with a shorter TTR,
      whereas higher cyclin G1 expression was related to a lower survival, suggesting
      that miR-122 might represent an effective molecular target for HCC. Our findings
      establish a basis toward the development of combined chemo- and miRNA-based
      therapy for HCC treatment.

PMID- 19584284
TI  - Progressive tumor formation in mice with conditional deletion of TGF-beta
      signaling in head and neck epithelia is associated with activation of the
      PI3K/Akt pathway.
AB  - The precise role of transforming growth factor (TGF)-beta signaling in head and
      neck squamous cell carcinoma (SCC) is not yet fully understood. Here, we report
      generation of an inducible head- and neck-specific knockout mouse model by
      crossing TGF-beta receptor I (Tgfbr1) floxed mice with K14-CreER(tam) mice. By
      applying tamoxifen to oral cavity of the mouse to induce Cre expression, we were
      able to conditionally delete Tgfbr1 in the mouse head and neck epithelia. On
      tumor induction with 7,12-dimethylbenz(a)anthracene (DMBA), 45% of Tgfbr1
      conditional knockout (cKO) mice (n = 42) developed SCCs in the head and neck area
      starting from 16 weeks after treatment. However, no tumors were observed in the
      control littermates. A molecular analysis revealed an enhanced proliferation and
      loss of apoptosis in the basal layer of the head and neck epithelia of Tgfbr1 cKO
      mice 4 weeks after tamoxifen and DMBA treatment. The most notable finding of our
      study is that the phosphoinositide 3-kinase (PI3K)/Akt pathway was activated in
      SCCs that developed in the Tgfbr1 cKO mice on inactivation of TGF-beta signaling
      through Smad2/3 and DMBA treatment. These observations suggest that activation of
      Smad-independent pathways may contribute cooperatively with inactivation of Smad
      dependent pathways to promote head and neck carcinogenesis in these mice. Our
      results revealed the critical role of the TGF-beta signaling pathway and its
      cross-talk with the PI3K/Akt pathway in suppressing head and neck carcinogenesis.

PMID- 19584285
TI  - Genomic characterization of esophageal squamous cell carcinoma from a high-risk
      population in China.
AB  - Genomic instability plays an important role in most human cancers. To
      characterize genomic instability in esophageal squamous cell carcinoma (ESCC), we
      examined loss of heterozygosity (LOH), copy number (CN) loss, CN gain, and gene
      expression using the Affymetrix GeneChip Human Mapping 500K (n = 30 cases) and
      Human U133A (n = 17 cases) arrays in ESCC cases from a high-risk region of China.
      We found that genomic instability measures varied widely among cases and
      separated them into two groups: a high-frequency instability group (two-thirds of
      all cases with one or more instability category of > or =10%) and a low-frequency
      instability group (one-third of cases with instability of <10%). Genomic
      instability also varied widely across chromosomal arms, with the highest
      frequency of LOH on 9p (33% of informative single nucleotide polymorphisms), CN
      loss on 3p (33%), and CN gain on 3q (48%). Twenty-two LOH regions were
      identified: four on 9p, seven on 9q, four on 13q, two on 17p, and five on 17q.
      Three CN loss regions-3p12.3, 4p15.1, and 9p21.3-were detected. Twelve CN gain
      regions were found, including six on 3q, one on 7q, four on 8q, and one on 11q.
      One of the most gene-rich of these CN gain regions was 11q13.1-13.4, where 26
      genes also had RNA expression data available. CN gain was significantly
      correlated with increased RNA expression in over 80% of these genes. Our findings
      show the potential utility of combining CN analysis and gene expression data to
      identify genes involved in esophageal carcinogenesis.

PMID- 19584286
TI  - Transcriptional output of the Salvador/warts/hippo pathway is controlled in
      distinct fashions in Drosophila melanogaster and mammalian cell lines.
AB  - The Salvador/Warts/Hippo (SWH) pathway is an important modulator of organ size,
      and deregulation of pathway activity can lead to cancer. Several SWH pathway
      components are mutated or expressed at altered levels in different human tumors
      including NF2, LATS1, LATS2, SAV1, and YAP. The SWH pathway regulates tissue
      growth by restricting the activity of the transcriptional coactivator protein
      known as Yorkie (Yki) in Drosophila melanogaster and Yes-associated protein (YAP)
      in mammals. Yki/YAP drives tissue growth in partnership with the Scalloped
      (Sd)/TEAD1-4 transcription factors. Yki/YAP also possesses two WW domains, which
      contact several proteins that have been suggested to either promote or inhibit
      the ability of Yki to induce transcription. To investigate the regulatory role of
      the Yki/YAP WW domains, we analyzed the functional consequence of mutating these
      domains. WW domain mutant YAP promoted transformation and migration of breast
      epithelial cells with increased potency, suggesting that WW domains mediate the
      inhibitory regulation of YAP in these cells. By contrast, the WW domains were
      required for YAP to promote NIH-3T3 cell transformation and for the ability of
      Yki to drive tissue growth in D. melanogaster and optimally activate Sd. This
      shows that Yki/YAP WW domains have distinct regulatory roles in different cell
      types and implies the existence of proteins that promote tissue growth in
      collaboration with Yki and Sd.

PMID- 19584287
TI  - The serine protease inhibitor protease nexin-1 controls mammary cancer metastasis
      through LRP-1-mediated MMP-9 expression.
AB  - Through their ability to degrade the extracellular matrix, proteases mediate
      cancer cell invasion and metastasis. Paradoxically, some serine protease
      inhibitors (serpins) are often overexpressed in human tumors. Using computational
      analysis, we found that the RNA level of protease nexin-1 (PN-1), a serpin that
      blocks numerous proteases activity, is significantly elevated in estrogen
      receptor-alpha-negative and in high-grade breast cancer. The in silico approach
      was complemented by mechanistic studies on two mammary cancer cell lines, the PN
      1-negative 168FARN cells and the PN-1-positive 4T1 cells, both of which form
      primary mammary tumors, but only 4T1 tumors are able to metastasize to the lungs.
      We show that treatment of 168FARN cells with PN-1 stimulates extracellular signal
      regulated kinase activation via low-density lipoprotein receptor-related protein
      1 (LRP-1) binding, resulting in increased matrix metalloproteinase (MMP)-9 RNA,
      protein, and secreted activity. PN-1-silenced 4T1 cells express low MMP-9 levels.
      Moreover, injection of PN-1-silenced cells into mice did not affect 4T1 primary
      mammary tumor outgrowth; however, the tumors had impaired metastatic potential,
      which could be restored by reexpressing soluble MMP-9 in the PN-1-silenced 4T1
      cells. Thus, using mammary tumor models, we describe a novel pathway whereby the
      serpin PN-1 by binding LRP-1 stimulates extracellular signal-regulated kinase
      signaling, MMP-9 expression, and metastatic spread of mammary tumors.
      Importantly, an analysis of 126 breast cancer patients revealed that those whose
      breast tumors had elevated PN-1 levels had a significantly higher probability to
      develop lung metastasis, but not metastasis to other sites, on relapse. These
      results suggest that PN-1 might become a prognostic marker in breast cancer.

PMID- 19584288
TI  - Kruppel-associated box domain-associated protein-1 as a latency regulator for
      Kaposi's sarcoma-associated herpesvirus and its modulation by the viral protein
      kinase.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) has been linked to the development
      of Kaposi's sarcoma, a major AIDS-associated malignancy, and to hematologic
      malignancies, including primary effusion lymphoma and multicentric Castleman's
      disease. Like other herpesviruses, KSHV is capable of both latent and lytic
      replication. Understanding the molecular details associated with this transition
      from latency to lytic replication is key to controlling virus spread and can
      affect the development of intervention strategies. Here, we report that Kruppel
      associated box domain-associated protein-1 (KAP-1)/transcriptional intermediary
      factor 1beta, a cellular transcriptional repressor that controls chromosomal
      remodeling, participates in the process of switching viral latency to lytic
      replication. Knockdown of KAP-1 by small interfering RNA leads to KSHV
      reactivation mediated by K-Rta, a key transcriptional regulator. In cells
      harboring latent KSHV, KAP-1 was associated with the majority of viral lytic-gene
      promoters. K-Rta overexpression induced the viral lytic cycle with concomitant
      reduction of KAP-1 binding to viral promoters. Association of KAP-1 with
      heterochromatin was modulated by both sumoylation and phosphorylation. During
      lytic replication of KSHV, KAP-1 was phosphorylated at Ser(824). Several lines of
      evidence directly linked the viral protein kinase to this post-translational
      modification. Additional studies showed that this phosphorylation of KAP-1
      produced a decrease in its sumoylation, consequently decreasing the ability of
      KAP-1 to condense chromatin on viral promoters. In summary, the cellular
      transcriptional repressor KAP-1 plays a role in regulating KSHV latency, and
      viral protein kinase modulates the chromatin remodeling function of this
      repressor.

PMID- 19584289
TI  - Nimotuzumab, an antitumor antibody that targets the epidermal growth factor
      receptor, blocks ligand binding while permitting the active receptor
      conformation.
AB  - Overexpression of the epidermal growth factor (EGF) receptor (EGFR) in cancer
      cells correlates with tumor malignancy and poor prognosis for cancer patients.
      For this reason, the EGFR has become one of the main targets of anticancer
      therapies. Structural data obtained in the last few years have revealed the
      molecular mechanism for ligand-induced EGFR dimerization and subsequent signal
      transduction, and also how this signal is blocked by either monoclonal antibodies
      or small molecules. Nimotuzumab (also known as h-R3) is a humanized antibody that
      targets the EGFR and has been successful in the clinics. In this work, we report
      the crystal structure of the Fab fragment of Nimotuzumab, revealing some unique
      structural features in the heavy variable domain. Furthermore, competition assays
      show that Nimotuzumab binds to domain III of the extracellular region of the
      EGFR, within an area that overlaps with both the surface patch recognized by
      Cetuximab (another anti-EGFR antibody) and the binding site for EGF. A computer
      model of the Nimotuzumab-EGFR complex, constructed by docking and molecular
      dynamics simulations and supported by mutagenesis studies, unveils a novel
      mechanism of action, with Nimotuzumab blocking EGF binding while still allowing
      the receptor to adopt its active conformation, hence warranting a basal level of
      signaling.

PMID- 19584290
TI  - MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3:
      potential implications for immune based therapy of human solid tumors.
AB  - B7-H3, a surface immunomodulatory glycoprotein, inhibits natural killer cells and
      T cells. The monoclonal antibody (mAb) 8H9 is specific for 4Ig-B7-H3, the long
      and principal form of B7-H3. Early results from radioimmunotherapy using 8H9 have
      shown promise in patients with metastatic solid tumors to the central nervous
      system. Whereas B7-H3 transcript was ubiquitously expressed in a wide spectrum of
      human solid tumors as well as human normal tissues, B7-H3 protein was
      preferentially expressed only in tumor tissues. By quantitative reverse
      transcription-PCR, all three isoforms of microRNA miR-29 (a, b, and c) were
      highly expressed in normal tissues. However, they were down-regulated in a broad
      spectrum of solid tumors, including neuroblastoma, sarcomas, brain tumors, and
      tumor cell lines. B7-H3 protein expression was inversely correlated with miR-29
      levels in both cell lines and tumor tissues tested. Using luciferase reporter
      assay, miR-29a was shown to directly target B7-H3 3' untranslated region, and
      knock-in and knockdown of miR-29a led to down-regulation and up-regulation,
      respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3
      protein expression has implications in immune escape by solid tumors.
      Differential modulation of this key immunoinhibitory molecule in tumor versus
      normal tissues may advance both cell-mediated immunotherapy and antibody-based
      targeted strategies using the B7-H3-specific mAb 8H9.

PMID- 19584291
TI  - Bone morphogenetic proteins 2 and 5 are down-regulated in adrenocortical
      carcinoma and modulate adrenal cell proliferation and steroidogenesis.
AB  - Bone morphogenetic proteins (BMP) have been shown to affect tumorigenesis in a
      variety of tumors. Quantitative PCR analysis revealed down-regulation of BMP2 and
      BMP5 in tissue samples from adrenocortical carcinoma and adrenocortical tumor
      cell lines compared with normal adrenal glands. Integrity of BMP-dependent
      pathways in these cell lines could be shown by activation of the Smad1/5/8
      pathway with subsequent increase of ID protein expression upon incubation with
      BMP2 or BMP5. On a functional level, BMP treatment resulted in inhibition of cell
      proliferation and viability in a dose- and time-dependent manner. This growth
      inhibitory effect was associated with BMP-dependent reduction of AKT
      phosphorylation under baseline conditions and under insulin-like growth factor
      costimulation. Furthermore, steroidogenic function, including melanocortin-2
      receptor and steroidogenic enzyme expressions, was profoundly reduced. In vitro
      demethylation treatment and overexpression of GATA6 resulted in reactivation of
      BMP-dependent pathways with concomitant modulation of steroidogenesis. Taken
      together, we show that loss of expression of members of the BMP family of ligands
      is a common finding in adrenocortical tumors and we provide evidence that BMP
      dependent pathways are likely to be involved in the modulation of the malignant
      and functional phenotype of adrenocortical cancer cells.

PMID- 19584292
TI  - Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3
      kinase/mammalian target of rapamycin inhibitor NVP-BEZ235.
AB  - The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)
      pathway mediates proliferation, survival, and drug resistance in multiple myeloma
      (MM) cells. Here, we tested the anti-MM activity of NVP-BEZ235 (BEZ235), which
      inhibits PI3K/Akt/mTOR signaling at the levels of PI3K and mTOR. 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric survival
      assays showed that MM cell lines exhibited dose- and time-dependent decreased
      viability after exposure to BEZ235 (IC(50), 25-800 nmol/L for 48 hours). MM cells
      highly sensitive (IC(50), <25 nmol/L) to BEZ235 (e.g., MM.1S, MM.1R, Dox40, and
      KMS-12-PE) included both lines sensitive and resistant to conventional
      (dexamethasone, cytotoxic chemotherapeutics) agents. Pharmacologically relevant
      BEZ235 concentrations (25-400 nmol/L) induced rapid commitment to and induction
      of MM.1S and OPM-2 cell death. Furthermore, normal donor peripheral blood
      mononuclear cells were less sensitive (IC(50), >800 nmol/L) than the majority of
      MM cell lines tested, suggesting a favorable therapeutic index. In addition,
      BEZ235 was able to target MM cells in the presence of exogenous interleukin-6,
      insulin-like growth factor-1, stromal cells, or osteoclasts, which are known to
      protect against various anti-MM agents. Molecular profiling revealed that BEZ235
      treatment decreased the amplitude of transcriptional signatures previously
      associated with myc, ribosome, and proteasome function, as well as high-risk MM
      and undifferentiated human embryonic stem cells. In vivo xenograft studies
      revealed significant reduction in tumor burden (P = 0.011) and survival (P =
      0.028) in BEZ235-treated human MM tumor-bearing mice. Combinations of BEZ235 with
      conventional (e.g., dexamethasone and doxorubicin) or novel (e.g., bortezomib)
      anti-MM agents showed lack of antagonism. These results indicate that BEZ235
      merits clinical testing, alone and in combination with other agents, in MM.

PMID- 19584293
TI  - Computational identification of a p38SAPK-regulated transcription factor network
      required for tumor cell quiescence.
AB  - The stress-activated kinase p38 plays key roles in tumor suppression and
      induction of tumor cell dormancy. However, the mechanisms behind these functions
      remain poorly understood. Using computational tools, we identified a
      transcription factor (TF) network regulated by p38alpha/beta and required for
      human squamous carcinoma cell quiescence in vivo. We found that p38
      transcriptionally regulates a core network of 46 genes that includes 16 TFs.
      Activation of p38 induced the expression of the TFs p53 and BHLHB3, while
      inhibiting c-Jun and FoxM1 expression. Furthermore, induction of p53 by p38 was
      dependent on c-Jun down-regulation. Accordingly, RNAi down-regulation of BHLHB3
      or p53 interrupted tumor cell quiescence, while down-regulation of c-Jun or FoxM1
      or overexpression of BHLHB3 in malignant cells mimicked the onset of quiescence.
      Our results identify components of the regulatory mechanisms driving p38-induced
      cancer cell quiescence. These may regulate dormancy of residual disease that
      usually precedes the onset of metastasis in many cancers.

PMID- 19584294
TI  - Human papillomavirus E7 oncoprotein overrides the tumor suppressor activity of
      p21Cip1 in cervical carcinogenesis.
AB  - The E7 oncoprotein of the high-risk human papillomaviruses (HPV) is thought to
      contribute to cervical carcinogenesis at least in part by abrogating cell cycle
      regulation. E7 can dysregulate the cell cycle through its interaction with
      several cellular proteins including the retinoblastoma suppressor protein pRb, as
      well as the cyclin-dependent kinase inhibitor p21(Cip1). Inactivation of pRb in
      cervical epithelia is not sufficient to explain the ability of E7 to cause
      cervical cancers in transgenic mice. In the current study, we focused on the role
      of p21(Cip1) in cervical cancer. Cervical disease was significantly increased in
      p21(-/-) mice compared with p21(+/+) mice, showing that p21(Cip1) can function as
      a tumor suppressor in this tissue. Importantly, the ability of E7 to induce
      cervical cancers was not significantly enhanced on the p21-null background,
      consistent with the hypothesis that the ability of E7 to inhibit p21(Cip1)
      contributes to its carcinogenic properties. Further supportive of this
      hypothesis, cervical carcinogenesis in mice expressing a mutant form of HPV-16
      E7, E7(CVQ), which fails to inactivate p21(Cip1), was significantly reduced
      compared with that in K14E7(WT) mice expressing wild-type HPV-16 E7. However,
      K14E7(CVQ) mice still displayed heightened levels of cervical carcinogenesis
      compared with that in nontransgenic mice, indicating that activities of E7
      besides its capacity to inactivate p21(Cip1) also contribute to cervical
      carcinogenesis. Taken together, we conclude that p21(Cip1) functions as a tumor
      suppressor in cervical carcinogenesis and that p21(Cip1) inactivation by HPV-16
      E7 partially contributes to the contribution of E7 to cervical carcinogenesis.

PMID- 19584297
TI  - Overexpression of platelet-derived growth factor-BB increases tumor pericyte
      content via stromal-derived factor-1alpha/CXCR4 axis.
AB  - Platelet-derived growth factor-BB (PDGF-BB) is a well-characterized growth factor
      displaying potent biological effects on angiogenesis. Recent studies reveal that
      overexpression of PDGF-BB within tumors results in increased pericyte coverage,
      suggesting that PDGF-BB signaling is also essential for the cancerous pericyte
      recruitment process. However, the molecular mechanism underlying this regulation
      remains obscure. In the current study, we show that tumor-derived PDGF-BB induces
      SDF-1alpha expression in endothelial cells (EC), resulting in the formation of
      SDF-1alpha chemotaxis gradient, which coincides with the PDGF-BB-induced pericyte
      recruitment during angiogenesis. PDGF-BB dramatically up-regulates SDF-1alpha
      secretion through the activation of PDGFRbeta in tumor-associated ECs, whereas
      this up-regulation can be substantially inhibited by either blockade of the
      phosphatidylinositol 3-kinase/Akt/mTOR pathway with chemical inhibitors or the
      inactivation of HIF-1alpha through small interfering RNA interference. On the
      other hand, we reveal that SDF-1alpha can increase pericytes motility in vitro.
      Blockade of the SDF-1alpha/CXCR4 axis prevents the PDGF-BB-induced pericyte
      recruitment not only in three in vitro recruitment models but also in the PDGF-BB
      overexpressing tumor xenograft models. These results highlight that the
      involvement of SDF-1alpha/CXCR4 axis is essential for the pericyte recruitment
      within the PDGF-BB-overexpressing tumors and raise the possibility that blockade
      of the SDF-1alpha/CXCR4 axis may provide a therapeutic synergy with
      antiangiogenic molecules that selectively target ECs.

PMID- 19584295
TI  - Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells
      in osteosarcoma.
AB  - We explored the nature of the tumor-initiating cell in osteosarcoma, a bone
      malignancy that predominately occurs in children. Previously, we observed
      expression of Oct-4, an embryonal transcriptional regulator, in osteosarcoma cell
      cultures and tissues. To examine the relationship between Oct-4 and
      tumorigenesis, cells from an osteosarcoma biopsy (OS521) were stably transfected
      with a plasmid containing the human Oct-4 promoter driving a green fluorescent
      protein (GFP) reporter to generate the transgenic line OS521Oct-4p. In culture,
      only approximately 24% of the OS521Oct-4p cells were capable of activating the
      transgenic Oct-4 promoter; yet, xenograft tumors generated in NOD/SCID mice
      contained approximately 67% GFP(+) cells, which selectively expressed the
      mesenchymal stem cell-associated surface antigens CD105 and ICAM-1. Comparison of
      the tumor-forming capacity of GFP-enriched and GFP-depleted cell fractions
      revealed that the GFP-enriched fractions were at least 100-fold more tumorigenic,
      capable of forming tumors at doses of <300 cells, and formed metastases in the
      lung. Clonal populations derived from a single Oct-4/GFP(+) cell were capable of
      forming tumors heterogeneous for Oct-4/GFP expression. These data are consistent
      with the cancer stem cell model of tumorigenesis in osteosarcoma and implicate a
      functional link between the capacity to activate an exogenous Oct-4 promoter and
      tumor formation. This osteosarcoma tumor-initiating cell appears highly prolific
      and constitutes a majority of the cell population in a primary xenograft tumor,
      which may provide a biological basis for the particular virulence of this type of
      cancer.

PMID- 19584296
TI  - Epithelial to mesenchymal transition contributes to drug resistance in pancreatic
      cancer.
AB  - A better understanding of drug resistance mechanisms is required to improve
      outcomes in patients with pancreatic cancer. Here, we characterized patterns of
      sensitivity and resistance to three conventional chemotherapeutic agents with
      divergent mechanisms of action [gemcitabine, 5-fluorouracil (5-FU), and
      cisplatin] in pancreatic cancer cells. Four (L3.6pl, BxPC-3, CFPAC-1, and
      SU86.86) were sensitive and five (PANC-1, Hs766T, AsPC-1, MIAPaCa-2, and MPanc96)
      were resistant to all three agents based on GI(50) (50% growth inhibition). Gene
      expression profiling and unsupervised hierarchical clustering revealed that the
      sensitive and resistant cells formed two distinct groups and differed in
      expression of specific genes, including several features of "epithelial to
      mesenchymal transition" (EMT). Interestingly, an inverse correlation between E
      cadherin and its transcriptional suppressor, Zeb-1, was observed in the gene
      expression data and was confirmed by real-time PCR. Independent validation
      experiment using five new pancreatic cancer cell lines confirmed that an inverse
      correlation between E-cadherin and Zeb-1 correlated closely with resistance to
      gemcitabine, 5-FU, and cisplatin. Silencing Zeb-1 in the mesenchymal lines not
      only increased the expression of E-cadherin but also other epithelial markers,
      such as EVA1 and MAL2, and restored drug sensitivity. Importantly,
      immunohistochemical analysis of E-cadherin and Zeb-1 in primary tumors confirmed
      that expression of the two proteins was mutually exclusive (P = 0.012).
      Therefore, our results suggest that Zeb-1 and other regulators of EMT may
      maintain drug resistance in human pancreatic cancer cells, and therapeutic
      strategies to inhibit Zeb-1 and reverse EMT should be evaluated.

PMID- 19584298
TI  - Analysis of the human cancer glycome identifies a novel group of tumor-associated
      N-acetylglucosamine glycan antigens.
AB  - The cell surface is covered by a dense layer of protein- and lipid-linked
      glycans. Although it has been known that distinct glycan structures are
      associated with cancer, the whole spectrum of cancer-associated glycans has
      remained undiscovered. In the present study, we analyzed the protein-linked
      cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometric glycan profiling of cancer patient tissue samples. In lung cancer,
      we detected accumulation of a novel group of tumor-associated glycans. These
      protein-linked glycans carried abnormal nonreducing terminal beta-N-acetyl-D
      glucosamine (GlcNAc) residues. A similar phenomenon was also detected in
      structural analyses of tumor-derived glycosphingolipids. This showed that glycan
      biosynthesis may dramatically change in cancer and that direct glycome analysis
      can detect the resulting marker glycans. Based on the structural knowledge, we
      further devised a covalent labeling technique for the detection of GlcNAc
      expressing tumors with a specific transferase enzyme. In normal tissues, terminal
      GlcNAc antigens are capped by galactosylation. Similarly to common cancer
      associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc
      antigens result from incomplete glycosylation. In conclusion, the identified
      terminal GlcNAc glycans should be recognized as a novel class of tumor markers.

PMID- 19584299
TI  - Efficient targeting of a SCID gene by an engineered single-chain homing
      endonuclease.
AB  - Sequence-specific endonucleases recognizing long target sequences are emerging as
      powerful tools for genome engineering. These endonucleases could be used to
      correct deleterious mutations or to inactivate viruses, in a new approach to
      molecular medicine. However, such applications are highly demanding in terms of
      safety. Mutations in the human RAG1 gene cause severe combined immunodeficiency
      (SCID). Using the I-CreI dimeric LAGLIDADG meganuclease as a scaffold, we
      describe here the engineering of a series of endonucleases cleaving the human
      RAG1 gene, including obligate heterodimers and single-chain molecules. We show
      that a novel single-chain design, in which two different monomers are linked to
      form a single molecule, can induce high levels of recombination while
      safeguarding more effectively against potential genotoxicity. We provide here the
      first demonstration that an engineered meganuclease can induce targeted
      recombination at an endogenous locus in up to 6% of transfected human cells.
      These properties rank this new generation of endonucleases among the best
      molecular scissors available for genome surgery strategies, potentially avoiding
      the deleterious effects of previous gene therapy approaches.

PMID- 19584302
TI  - Differential contribution of SNARE-dependent exocytosis to inflammatory
      potentiation of TRPV1 in nociceptors.
AB  - Potentiation of the pain-integrator ion channel transient receptor potential
      vanilloid type 1 (TRPV1) underlies thermal hyperalgesia mediated by a variety of
      proinflammatory factors. Two complementary mechanisms of TRPV1 inflammatory
      sensitization have been proposed, namely a decrease of its activation threshold
      and an increment of its surface expression in nociceptors. Here we investigated
      the involvement of regulated exocytosis to the inflammatory sensitization of
      TRPV1 in rat neonatal dorsal root ganglion neurons by proalgesic agents. The
      contribution of soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE)-dependent exocytosis was evaluated using a small peptide
      patterned after the synaptosomal-associated protein of 25 kDa (SNAP-25) protein
      that acts as a specific and potent inhibitor of neuronal exocytosis. We found
      that TRPV1 sensitization mediated by nerve growth factor, ATP, and IGF-I was
      accompanied by a higher channel expression in the neuronal plasma membrane, which
      was prevented by blockade of regulated exocytosis. In contrast, TRPV1
      sensitization caused by bradykinin, IL-1beta, and artemin was insensitive to
      inhibition of SNARE-dependent vesicular fusion and was not due to an increase in
      TRPV1 surface expression. Therefore, it appears that some, but not all,
      proinflammatory agents sensitize rat nociceptors by promoting the recruitment of
      TRPV1 channels to the neuronal surface. These findings support the tenet that
      SNARE complex-mediated exocytosis of TRPV1 may be a valid therapeutic target to
      treat inflammatory pain.

PMID- 19584301
TI  - The sunburn response in human skin is characterized by sequential eicosanoid
      profiles that may mediate its early and late phases.
AB  - Sunburn is a commonly occurring acute inflammatory process, with dermal
      vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B
      induced hydrolysis of membrane phospholipids releases polyunsaturated fatty
      acids, and their subsequent metabolism by cyclooxygenases (COXs) and
      lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different
      stages of the inflammation. Our objective was to identify candidate eicosanoids
      formed during the sunburn reaction in relation to its clinical and histological
      course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined
      expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI
      MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and
      leukocyte markers, while quantifying clinical erythema. We show that vasodilatory
      prostaglandins (PGs) PGE(2), PGF(2alpha), and PGE(3) accompany the erythema in
      the first 24-48 h, associated with increased COX-2 expression at 24 h. Novel,
      potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic
      acid (HETE) are elevated from 4 to 72 h, in association with peak dermal
      neutrophil influx at 24 h, and increased dermal CD3(+) lymphocytes and 12- and 15
      LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later
      expression, peaking at 72 h. Sunburn is characterized by overlapping sequential
      profiles of increases in COX products followed by LOX products that may regulate
      subsequent events and ultimately its resolution.

PMID- 19584300
TI  - Structural changes in intermediate filament networks alter the activity of
      insulin-degrading enzyme.
AB  - The intermediate filament (IF) protein nestin coassembles with vimentin and
      promotes the disassembly of these copolymers when vimentin is hyperphosphorylated
      during mitosis. The aim of this study is to determine the function of these
      nonfilamentous particles by identifying their interacting partners. In this
      study, we report that these disassembled vimentin/nestin complexes interact with
      insulin degrading enzyme (IDE). Both vimentin and nestin interact with IDE in
      vitro, but vimentin binds IDE with a higher affinity than nestin. Although the
      interaction between vimentin and IDE is enhanced by vimentin phosphorylation at
      Ser-55, the interaction between nestin and IDE is phosphorylation independent.
      Further analyses show that phosphorylated vimentin plays the dominant role in
      targeting IDE to the vimentin/nestin particles in vivo, while the requirement for
      nestin is related to its ability to promote vimentin IF disassembly. The binding
      of IDE to either nestin or phosphorylated vimentin regulates IDE activity
      differently, depending on the substrate. The insulin degradation activity of IDE
      is suppressed approximately 50% by either nestin or phosphorylated vimentin,
      while the cleavage of bradykinin-mimetic peptide by IDE is increased 2- to 3
      fold. Taken together, our data demonstrate that the nestin-mediated disassembly
      of vimentin IFs generates a structure capable of sequestering and modulating the
      activity of IDE.

PMID- 19584303
TI  - Characterization of human adult stem-cell populations isolated from visceral and
      subcutaneous adipose tissue.
AB  - Adipose tissue is a dynamic endocrine organ with a central role in metabolism
      regulation. Functional differences in adipose tissue seem associated with the
      regional distribution of fat depots, in particular in subcutaneous and visceral
      omental pads. Here, we report for the first time the isolation of human adipose
      derived adult stem cells from visceral omental and subcutaneous fat (V-ASCs and S
      ASCs, respectively) from the same subject. Immunophenotyping shows that plastic
      culturing selects homogeneous cell populations of V-ASCs and S-ASCs from the
      corresponding stromal vascular fractions (SVFs), sharing typical markers of
      mesenchymal stem cells. Electron microscopy and electrophysiological and real
      time RT-PCR analyses confirm the mesenchymal stem nature of both V-ASCs and S
      ASCs, while no significant differences in a limited pattern of cytokine/chemokine
      expression can be detected. Similar to S-ASCs, V-ASCs can differentiate in vitro
      toward adipogenic, osteogenic, chondrogenic, muscular, and neuronal lineages, as
      demonstrated by histochemical, immunofluorescence, real-time RT-PCR, and
      electrophysiological analyses, suggesting the multipotency of such adult stem
      cells. Our data demonstrate that both visceral and subcutaneous adipose tissues
      are a source of pluripotent stem cells with multigermline potential. However, the
      visceral rather than the subcutaneous ASC could represent a more appropriate in
      vitro cell model for investigating the molecular mechanisms implicated in the
      pathophysiology of metabolic disorders such as obesity.

PMID- 19584305
TI  - Complete focal adhesion kinase deficiency in the mammary gland causes ductal
      dilation and aberrant branching morphogenesis through defects in Rho kinase
      dependent cell contractility.
AB  - The adult, virgin mammary gland is a highly organized branched ductal network
      comprising two major cell types: myoepithelial and luminal epithelial cells. To
      study the role and mechanism of focal adhesion kinase (FAK)-mediated signaling in
      mammary gland development and differentiation, we used a conditional Fak-knockout
      mammary epithelial cell (MEC) transplantation model. Conditional Cre recombinase
      (Cre)-mediated Fak deletion in primary cultured MECs isolated from
      FAK(lox/lox)/Rosa26Cre-ERT2 donor mice caused loss of FAK in all mammary cells.
      Transplantation of Fak-knockout MECs in a cleared mammary fat pad of immune
      deficient recipient mice resulted in development of new but dilated virgin ducts
      with a disrupted myoepithelial and luminal epithelial cell multilayer and
      aberrant ductal morphogenesis during pregnancy. In the absence of FAK, MECs
      spread poorly, showed enhanced Rho kinase (ROCK)-mediated cytoskeletal
      contractility, and failed to respond to receptor-mediated cytoskeletal
      remodeling. Likewise, FAK deficiency fully inhibited branching morphogenesis of
      mammary gland organoids in a ROCK-dependent manner. Altogether these data suggest
      a model in which FAK coordinates contractile forces in MECs to maintain the
      bilayered cellular organization of myoepithelial and luminal epithelial cells in
      ducts, thus allowing proper mammary gland development and function.

PMID- 19584304
TI  - Inactivation of klotho function induces hyperphosphatemia even in presence of
      high serum fibroblast growth factor 23 levels in a genetically engineered
      hypophosphatemic (Hyp) mouse model.
AB  - Hyp mice possess a mutation that inactivates the phosphate-regulating gene, which
      is homologous to the endopeptidases of the X-chromosome (PHEX). The mutation is
      associated with severe hypophosphatemia due to excessive urinary phosphate
      wasting. Such urinary phosphate wasting in Hyp mice is associated with an
      increased serum accumulation of fibroblast growth factor (FGF) 23. We wanted to
      determine the biological significance of increased serum FGF23 levels and
      concomitant hypophosphatemia in Hyp mice and to evaluate whether FGF23 activity
      could be modified by manipulating klotho (a cofactor of FGF23 signaling). We
      generated Hyp and klotho double-mutant mice (Hyp/klotho(-/-)). Severe
      hypophosphatemia of Hyp mice was reversed to hyperphosphatemia in Hyp/klotho(-/-)
      double mutants, despite the fact that the double mutants showed significantly
      increased serum levels of FGF23. Hyperphosphatemia in Hyp/klotho(-/-) mice was
      associated with increased renal expression of sodium/phosphate cotransporter 2a
      (NaPi2a) protein. Exogenous injection of bioactive parathyroid hormone 1-34 down
      regulated renal expression of NaPi2a and consequently reduced serum levels of
      phosphate in Hyp/klotho(-/-) mice. Moreover, in contrast to the Hyp mice, the
      Hyp/klotho(-/-) mice showed significantly higher serum levels of 1,25
      dihydroxyvitamin D and developed extensive calcification in soft tissues and
      vascular walls. Furthermore, compared with the Hyp mice, Hyp/klotho(-/-) mice
      were smaller in size, showed features of generalized tissue atrophy, and
      generally died by 15-20 wk of age. Our in vivo studies provide genetic evidence
      for a pathological role of increased FGF23 activities in regulating abnormal
      phosphate homeostasis in Hyp mice. Moreover, these results suggest that even when
      serum levels of FGF23 are significantly high, in the absence of klotho, FGF23 is
      unable to regulate systemic phosphate homeostasis. Our in vivo observations have
      significant clinical implications in diseases associated with increased FGF23
      activity and suggest that the functions of FGF23 can be therapeutically modulated
      by manipulating the effects of klotho.

PMID- 19584306
TI  - Functional selectivity of natural and synthetic prostaglandin EP4 receptor
      ligands.
AB  - Classically, the prostaglandin E(2) (PGE(2)) receptor EP(4) has been classified
      as coupling to the Galpha(s) subunit, leading to intracellular cAMP increases.
      However, EP(4) signaling has been revealed to be more complex and also involves
      coupling to pertussis toxin-sensitive Galpha(i) proteins and beta-arrestin
      mediated effects. There are now many examples of selective activation of
      independent pathways by G protein-coupled receptor (GPCR) ligands, a concept
      referred to as functional selectivity. Because most EP(4) ligands had thus far
      only been functionally characterized by their ability to stimulate cAMP
      production, we systematically determined the potencies and efficacies of a panel
      of EP(4) ligands for activation of Galpha(s), Galpha(i), and beta-arrestin
      relative to the endogenous ligand PGE(2). For this purpose, we adapted three
      bioluminescence resonance energy transfer (BRET) assays to evaluate the
      respective pathways in living cells. Our results suggest considerable functional
      selectivity among the tested, structurally related agonists. PGE(2) was the most
      selective in activating Galpha(s), whereas PGF(2alpha) and PGE(1) alcohol were
      the most biased for activating Galpha(i1) and beta-arrestin, respectively. We
      observed reversal in order of potencies between beta-arrestin 2 and Galpha(i1)
      functional assays comparing PGE(1) alcohol and either PGF(2alpha), PGD(2), or 7
      [(1R,2R)-2-[(E,3R)-3-hydroxy-4-(phenoxy)but-1-enyl]-5-oxocyclopentyl]heptanoic
      acid (M&B28767). Most ligands were full agonists for the three pathways tested.
      Our results have implications for the use of PGE(2) analogs in experimental and
      possibly clinical settings, because their activity spectra on EP(4) differ from
      that of the native agonist. The BRET-based methodology used for this first
      systematic assessment of a set of EP(4) agonists should be applicable for the
      study of other GPCRs.

PMID- 19584307
TI  - Rescue of functional F508del cystic fibrosis transmembrane conductance regulator
      by vasoactive intestinal peptide in the human nasal epithelial cell line
      JME/CF15.
AB  - F508del is the most common cystic fibrosis-causing mutation that induces early
      degradation and poor trafficking of cystic fibrosis transmembrane conductance
      regulator (CFTR) chloride channels to the apical membrane of epithelial cells.
      Our previous work in bronchial serous cells showed that vasoactive intestinal
      peptide (VIP) stimulation of the VPAC(1) receptor enhances CFTR-dependent
      chloride secretion by increasing its membrane insertion by a protein kinase C
      (PKC)-dependent pathway. In the present study, we investigated the effect of VIP
      on F508del-CFTR activity and membrane insertion in the human nasal epithelial
      cell line JME/CF15, which also expresses the VPAC(1) receptor. At reduced
      temperature (27 degrees C), which rescues F508del-CFTR trafficking, acute
      stimulation by VIP of rescued F508del-CFTR channels was protein kinase A (PKA)-
      and PKC-dependent. One hour of treatment with VIP strongly increased F508del-CFTR
      activity, with iodide efflux peaks three times higher than with untreated cells.
      At 37 degrees C, VIP-treated cells, but not untreated controls, showed
      significant iodide efflux peaks that were sensitive to the CFTR inhibitor 3-[(3
      trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone
      (CFTR(inh)-172). Immunostaining, biotinylation assays, and Western blots
      confirmed a VIP-induced maturation and membrane insertion of F508del-CFTR at 37
      degrees C. The corrector effect of VIP was abolished by the PKA inhibitor N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamidedihydrochloride (H89), whereas
      Galpha(s) stimulation by cholera toxin significantly increased F508del-CFTR
      trafficking. On the other hand, membrane localization, but not maturation, of
      F508del-CFTR was significantly reduced by the PKC inhibitor bisindolylmaleimide X
      and the G(i/o) protein inhibitor pertussis toxin. VIP treatment had no effect on
      intracellular calcium or proteasome activity. These results indicate that, in
      human nasal cells, VIP rescues trafficking and membrane insertion of functional
      F508del-CFTR channels at physiological temperature by stimulating both PKA- and
      PKC-dependent pathways.

PMID- 19584308
TI  - A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired
      insulin secretion.
AB  - OBJECTIVE: Two independent genome-wide association studies for type 2 diabetes in
      Japanese subjects have recently identified common variants in the KCNQ1 gene that
      are strongly associated with type 2 diabetes. Here we studied whether a common
      variant in KCNQ1 would influence BMI as well as insulin secretion and action and
      predict future type 2 diabetes in subjects from Sweden and Finland. RESEARCH
      DESIGN AND METHODS: Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was
      studied in 2,830 type 2 diabetic case subjects and 3,550 control subjects from
      Sweden (Malmo Case-Control) and prospectively in 16,061 individuals from the
      Malmo Preventive Project (MPP). Association between genotype and insulin
      secretion/action was assessed cross- sectionally in 3,298 nondiabetic subjects
      from the Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia Study and
      longitudinally in 2,328 nondiabetic subjects from the Botnia Prospective Study
      (BPS). KCNQ1 expression (n = 18) and glucose-stimulated insulin secretion (n =
      19) were measured in human islets from nondiabetic cadaver donors. RESULTS: The C
      allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes
      in both the Malmo Case-Control (odds ratio 1.23 [95% CI 1.12-1.34]; P = 5.6 x 10(
      6)) and the prospective (1.14 [1.06-1.22]; P = 4.8 x 10(-4)) studies.
      Furthermore, the C-allele was associated with decreased insulin secretion
      (corrected insulin response [CIR] P = 0.013; disposition index [DI] P = 0.013) in
      the PPP-Botnia Study and in the BPS at baseline (CIR P = 3.6 x 10(-4); DI P =
      0.0058) and after follow-up (CIR P = 0.0018; DI P = 0.0030). C-allele carriers
      showed reduced glucose-stimulated insulin secretion in human islets (P = 2.5 x
      10(-6)). CONCLUSIONS: A common variant in the KCNQ1 gene is associated with
      increased risk of future type 2 diabetes in Scandinavians, which partially can be
      explained by an effect on insulin secretion.

PMID- 19584309
TI  - Functional brain connectivity and neurocognitive functioning in patients with
      long-standing type 1 diabetes with and without microvascular complications: a
      magnetoencephalography study.
AB  - OBJECTIVE: Hyperglycemia-associated microvascular disease may underlie changes in
      cerebral functioning and cognitive performance in patients with type 1 diabetes.
      Functional connectivity, an indicator of functional interactions and information
      exchange between brain regions, provides a measure of cerebral functioning. This
      study addresses functional connectivity and cognition in type 1 diabetic patients
      with and without proliferative retinopathy, relative to healthy control subjects,
      using magnetoencephalography. RESEARCH DESIGN AND METHODS: Fluctuations in
      magnetic field at scalp for Delta, theta, lower and upper alpha, beta, and lower
      and upper gamma frequency bands were measured using magnetoencephalography.
      Synchronization likelihood, a measure of functional connectivity, was computed.
      Using neuropsychological tests, cognitive functioning was assessed and its
      associations with functional connectivity were determined. RESULTS: Compared with
      control subjects, type 1 diabetic patients performed poorer on general cognitive
      ability, information processing speed, and motor speed, irrespective of their
      microvascular complication status. Functional connectivity, however, was lowest
      for type 1 diabetic patients with retinopathy, compared with type 1 diabetic
      patients without microvascular complications and control subjects, whereas type 1
      diabetic patients without microvascular complications showed an increase relative
      to control subjects. Positive associations were found between functional
      connectivity and executive functioning, memory, information processing speed,
      motor speed, and attention. CONCLUSIONS: Compared with healthy control subjects,
      functional connectivity and cognition differed in type 1 diabetic patients
      irrespective of microvascular complication status, indicating that chronic
      hyperglycemia, among other factors, may negatively affect brain functioning even
      before microvascular damage becomes manifest. The association found between
      synchronization likelihood and cognition suggests functional connectivity plays a
      significant role in cognitive functioning.

PMID- 19584310
TI  - Foxo1 links hyperglycemia to LDL oxidation and endothelial nitric oxide synthase
      dysfunction in vascular endothelial cells.
AB  - OBJECTIVE: Atherosclerotic cardiovascular disease is the leading cause of death
      among people with diabetes. Generation of oxidized LDLs and reduced nitric oxide
      (NO) availability because of endothelial NO synthase (eNOS) dysfunction are
      critical events in atherosclerotic plaque formation. Biochemical mechanism
      leading from hyperglycemia to oxLDL formation and eNOS dysfunction is unknown.
      RESEARCH DESIGN AND METHODS: We show that glucose, acting through oxidative
      stress, activates the transcription factor Foxo1 in vascular endothelial cells.
      RESULTS: Foxo1 promotes inducible NOS (iNOS)-dependent NO-peroxynitrite
      generation, which leads in turn to LDL oxidation and eNOS dysfunction. We
      demonstrate that Foxo1 gain-of-function mimics the effects of hyperglycemia on
      this process, whereas conditional Foxo1 knockout in vascular endothelial cells
      prevents it. CONCLUSIONS: The findings reveal a hitherto unsuspected role of the
      endothelial iNOS-NO-peroxynitrite pathway in lipid peroxidation and eNOS
      dysfunction and suggest that Foxo1 activation in response to hyperglycemia brings
      about proatherogenic changes in vascular endothelial cell function.

PMID- 19584311
TI  - Ethyl pyruvate administration inhibits  hepatic tumor growth.
AB  - EP is a potent inhibitor of HMGB1 release that has significant anti-inflammatory
      activities and exerts a protective effect in animal models of inflammation. As
      inflammation is linked to cancer growth, we hypothesized that EP would have anti
      tumor activity and explored its effects in a liver tumor model. Mice injected
      intraportally with MC38 colorectal cancer cells led to the growth of visible
      hepatic tumors within 2 weeks. Pretreatment with EP 30 min prior to infusion of
      tumor cells and continuing daily for 9 days inhibited tumor growth significantly
      in a dose-dependent manner, with 80 mg/kg EP achieving >70% reduction in the
      number of tumor nodules when compared with untreated animals. Delayed treatment
      with EP also suppressed tumor growth significantly, although to a lesser extent.
      Tumors had early, marked leukocytic infiltrates, and EP administration decreased
      innate (NK cells, monocytes) and adaptive (T and B cell lymphocytic) immune cell
      infiltrates acutely and significantly in the liver. Serum IL-6 and HMGB1 levels,
      which were elevated following tumor injection, were decreased significantly in EP
      treated animals. Tumors showed an increase in apoptosis in EP treated mice, and
      tumor cells treated in vitro with EP had marked increases in LC3-II and cleaved
      PARP, consistent with enhanced autophagic flux and apoptosis. Thus, EP inhibition
      of tumor growth in the liver was mediated by tumor (induction of apoptosis) and
      host (decreased inflammation) effects. EP administration may have a therapeutic
      role in the treatment of cancer in conjunction with other therapeutic agents.

PMID- 19584312
TI  - Lung parenchymal mechanics in health and disease.
AB  - The mechanical properties of lung tissue are important determinants of lung
      physiological functions. The connective tissue is composed mainly of cells and
      extracellular matrix, where collagen and elastic fibers are the main determinants
      of lung tissue mechanical properties. These fibers have essentially different
      elastic properties, form a continuous network along the lungs, and are
      responsible for passive expiration. In the last decade, many studies analyzed the
      relationship between tissue composition, microstructure, and macrophysiology,
      showing that the lung physiological behavior reflects both the mechanical
      properties of tissue individual components and its complex structural
      organization. Different lung pathologies such as acute respiratory distress
      syndrome, fibrosis, inflammation, and emphysema can affect the extracellular
      matrix. This review focuses on the mechanical properties of lung tissue and how
      the stress-bearing elements of lung parenchyma can influence its behavior.

PMID- 19584313
TI  - LKB1 and AMPK family signaling: the intimate link between cell polarity and
      energy metabolism.
AB  - Research on the LKB1 tumor suppressor protein mutated in cancer-prone Peutz
      Jeghers patients has continued at a feverish pace following exciting developments
      linking energy metabolism and cancer development. This review summarizes the
      current state of research on the LKB1 tumor suppressor. The weight of the
      evidence currently indicates an evolutionary conserved role for the protein in
      the regulation of various aspects of cellular polarity and energy metabolism. We
      focus on studies examining the concept that both cellular polarity and energy
      metabolism are regulated through the conserved LKB1-AMPK signal transduction
      pathway. Recent studies from a variety of model organisms have given new insight
      into the mechanism of polyp development and cancer formation in Peutz-Jeghers
      patients and the role of LKB1 mutation in sporadic tumorigenesis. Conditional
      LKB1 mouse models have outlined a tissue-dependent context for pathway activation
      and suggest that LKB1 may affect different AMPK isoforms independently.
      Elucidation of the molecular mechanism responsible for Peutz-Jeghers syndrome
      will undoubtedly reveal important insight into cancer development in the larger
      population.

PMID- 19584314
TI  - Mitochondrial dynamics in mammalian health and disease.
AB  - The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and
      chondros, grain) illustrates that the heterogeneity of mitochondrial morphology
      has been known since the first descriptions of this organelle. Such a
      heterogeneous morphology is explained by the dynamic nature of mitochondria.
      Mitochondrial dynamics is a concept that includes the movement of mitochondria
      along the cytoskeleton, the regulation of mitochondrial architecture (morphology
      and distribution), and connectivity mediated by tethering and fusion/fission
      events. The relevance of these events in mitochondrial and cell physiology has
      been partially unraveled after the identification of the genes responsible for
      mitochondrial fusion and fission. Furthermore, during the last decade, it has
      been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1)
      cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer
      disease/autosomal dominant optic atrophy). In addition, other diseases such as
      type 2 diabetes or vascular proliferative disorders show impaired MFN2
      expression. Altogether, these findings have established mitochondrial dynamics as
      a consolidated area in cellular physiology. Here we review the most significant
      findings in the field of mitochondrial dynamics in mammalian cells and their
      implication in human pathologies.

PMID- 19584315
TI  - Hyperpolarization-activated cation channels: from genes to function.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a
      small subfamily of proteins within the superfamily of pore-loop cation channels.
      In mammals, the HCN channel family comprises four members (HCN1-4) that are
      expressed in heart and nervous system. The current produced by HCN channels has
      been known as I(h) (or I(f) or I(q)). I(h) has also been designated as pacemaker
      current, because it plays a key role in controlling rhythmic activity of cardiac
      pacemaker cells and spontaneously firing neurons. Extensive studies over the last
      decade have provided convincing evidence that I(h) is also involved in a number
      of basic physiological processes that are not directly associated with
      rhythmicity. Examples for these non-pacemaking functions of I(h) are the
      determination of the resting membrane potential, dendritic integration, synaptic
      transmission, and learning. In this review we summarize recent insights into the
      structure, function, and cellular regulation of HCN channels. We also discuss in
      detail the different aspects of HCN channel physiology in the heart and nervous
      system. To this end, evidence on the role of individual HCN channel types arising
      from the analysis of HCN knockout mouse models is discussed. Finally, we provide
      an overview of the impact of HCN channels on the pathogenesis of several diseases
      and discuss recent attempts to establish HCN channels as drug targets.

PMID- 19584316
TI  - Aneuploidy: from a physiological mechanism of variance to Down syndrome.
AB  - Quantitative differences in gene expression emerge as a significant source of
      variation in natural populations, representing an important substrate for
      evolution and accounting for a considerable fraction of phenotypic diversity.
      However, perturbation of gene expression is also the main factor in determining
      the molecular pathogenesis of numerous aneuploid disorders. In this review, we
      focus on Down syndrome (DS) as the prototype of "genomic disorder" induced by
      copy number change. The understanding of the pathogenicity of the extra genomic
      material in trisomy 21 has accelerated in the last years due to the recent
      advances in genome sequencing, comparative genome analysis, functional genome
      exploration, and the use of model organisms. We present recent data on the role
      of genome-altering processes in the generation of diversity in DS neural
      phenotypes focusing on the impact of trisomy on brain structure and mental
      retardation and on biological pathways and cell types in target brain regions
      (including prefrontal cortex, hippocampus, cerebellum, and basal ganglia). We
      also review the potential that genetically engineered mouse models of DS bring
      into the understanding of the molecular biology of human learning disorders.

PMID- 19584317
TI  - From pheromones to behavior.
AB  - In recent years, considerable progress has been achieved in the comprehension of
      the profound effects of pheromones on reproductive physiology and behavior.
      Pheromones have been classified as molecules released by individuals and
      responsible for the elicitation of specific behavioral expressions in members of
      the same species. These signaling molecules, often chemically unrelated, are
      contained in body fluids like urine, sweat, specialized exocrine glands, and
      mucous secretions of genitals. The standard view of pheromone sensing was based
      on the assumption that most mammals have two separated olfactory systems with
      different functional roles: the main olfactory system for recognizing
      conventional odorant molecules and the vomeronasal system specifically dedicated
      to the detection of pheromones. However, recent studies have reexamined this
      traditional interpretation showing that both the main olfactory and the
      vomeronasal systems are actively involved in pheromonal communication. The
      current knowledge on the behavioral, physiological, and molecular aspects of
      pheromone detection in mammals is discussed in this review.

PMID- 19584319
TI  - Transglutaminases and disease: lessons from genetically engineered mouse models
      and inherited disorders.
AB  - The human transglutaminase (TG) family consists of a structural protein, protein
      4.2, that lacks catalytic activity, and eight zymogens/enzymes, designated factor
      XIII-A (FXIII-A) and TG1-7, that catalyze three types of posttranslational
      modification reactions: transamidation, esterification, and hydrolysis. These
      reactions are essential for biological processes such as blood coagulation, skin
      barrier formation, and extracellular matrix assembly but can also contribute to
      the pathophysiology of various inflammatory, autoimmune, and degenerative
      conditions. Some members of the TG family, for example, TG2, can participate in
      biological processes through actions unrelated to transamidase catalytic
      activity. We present here a comprehensive review of recent insights into the
      physiology and pathophysiology of TG family members that have come from studies
      of genetically engineered mouse models and/or inherited disorders. The review
      focuses on FXIII-A, TG1, TG2, TG5, and protein 4.2, as mice deficient in TG3,
      TG4, TG6, or TG7 have not yet been reported, nor have mutations in these proteins
      been linked to human disease.

PMID- 19584320
TI  - AMPK in Health and Disease.
AB  - The function and survival of all organisms is dependent on the dynamic control of
      energy metabolism, when energy demand is matched to energy supply. The AMP
      activated protein kinase (AMPK) alphabetagamma heterotrimer has emerged as an
      important integrator of signals that control energy balance through the
      regulation of multiple biochemical pathways in all eukaryotes. In this review, we
      begin with the discovery of the AMPK family and discuss the recent structural
      studies that have revealed the molecular basis for AMP binding to the enzyme's
      gamma subunit. AMPK's regulation involves autoinhibitory features and
      phosphorylation of both the catalytic alpha subunit and the beta-targeting
      subunit. We review the role of AMPK at the cellular level through examination of
      its many substrates and discuss how it controls cellular energy balance. We look
      at how AMPK integrates stress responses such as exercise as well as nutrient and
      hormonal signals to control food intake, energy expenditure, and substrate
      utilization at the whole body level. Lastly, we review the possible role of AMPK
      in multiple common diseases and the role of the new age of drugs targeting AMPK
      signaling.

PMID- 19584321
TI  - A 62-year-old woman with skin cancer who experienced wrong-site surgery: review
      of medical error.
AB  - After a life-threatening complication of an injection for neck pain several years
      ago, Ms W experienced a wrong-site surgery to remove a squamous cell lesion from
      her nose, followed by pain, distress, and shaken trust in clinicians. Her
      experience highlights the challenges of communicating with patients after errors.
      Harmful medical errors occur relatively frequently. Gaps exist between patients'
      expectations for disclosure and apology and physicians' ability to deliver
      disclosures well. This discrepancy reflects clinicians' fear of litigation,
      concern that disclosure might harm patients, and lack of confidence in disclosure
      skills. Many institutions are developing disclosure programs, and some are
      reporting success in coupling disclosures with early offers of compensation to
      patients. However, much has yet to be learned about effective disclosure
      strategies. Important future developments include increased emphasis on
      institutions' responsibility for disclosure, involving trainees and other team
      members in disclosure, and strengthening the relationship between disclosure and
      quality improvement.

PMID- 19584322
TI  - Oncology's first Phase 0 trial.

PMID- 19584323
TI  - Laparoscopic versus open surgery in cancer: new studies add data to debate.

PMID- 19584325
TI  - Electronic medical records: oncology practices take the plunge.

PMID- 19584324
TI  - JAK2 inhibitors: not the next imatinib but researchers see other possibilities.

PMID- 19584318
TI  - Vascular extracellular matrix and arterial mechanics.
AB  - An important factor in the transition from an open to a closed circulatory system
      was a change in vessel wall structure and composition that enabled the large
      arteries to store and release energy during the cardiac cycle. The component of
      the arterial wall in vertebrates that accounts for these properties is the
      elastic fiber network organized by medial smooth muscle. Beginning with the onset
      of pulsatile blood flow in the developing aorta, smooth muscle cells in the
      vessel wall produce a complex extracellular matrix (ECM) that will ultimately
      define the mechanical properties that are critical for proper function of the
      adult vascular system. This review discusses the structural ECM proteins in the
      vertebrate aortic wall and will explore how the choice of ECM components has
      changed through evolution as the cardiovascular system became more advanced and
      pulse pressure increased. By correlating vessel mechanics with physiological
      blood pressure across animal species and in mice with altered vessel compliance,
      we show that cardiac and vascular development are physiologically coupled, and we
      provide evidence for a universal elastic modulus that controls the parameters of
      ECM deposition in vessel wall development. We also discuss mechanical models that
      can be used to design better tissue-engineered vessels and to test the efficacy
      of clinical treatments.

PMID- 19584326
TI  - StatBite: 2007 vs. 2008: Electronic Medical Records Adoption in United States'
      Practices.

PMID- 19584327
TI  - Underlying causes of the black-white racial disparity in breast cancer mortality:
      a population-based analysis.
AB  - BACKGROUND: In the United States, a black-to-white disparity in age-standardized
      breast cancer mortality rates emerged in the 1980s and has widened since then.
      METHODS: To further explore this racial disparity, black-to-white rate ratios
      (RRs(BW)) for mortality, incidence, hazard of breast cancer death, and incidence
      based mortality (IBM) were investigated using data from the National Cancer
      Institute's Surveillance, Epidemiology, and End Results program on 244 786 women
      who were diagnosed with breast cancer from January 1990 through December 2003 and
      followed through December 2004. A counterfactual approach was used to examine the
      expected IBM RRs(BW), assuming equal distributions for estrogen receptor (ER)
      expression, and/or equal hazard rates of breast cancer death, among black and
      white women. RESULTS: From 1990 through 2004, mortality RR(BW) was greater than
      1.0 and widened over time (age-standardized breast cancer mortality rates fell
      from 36 to 29 per 100 000 for blacks and from 30 to 22 per 100 000 for whites).
      In contrast, incidence RR(BW) was generally less than 1.0. Absolute hazard rates
      of breast cancer death declined substantially for ER-positive tumors and modestly
      for ER-negative tumors but were persistently higher for blacks than whites.
      Equalizing the distributions of ER expression in blacks and whites decreased the
      IBM RR(BW) slightly. Interestingly, the black-to-white disparity in IBM RR(BW)
      was essentially eliminated when hazard rates of breast cancer death were matched
      within each ER category. CONCLUSIONS: The black-to-white disparity in age
      standardized breast cancer mortality was largely driven by the higher hazard
      rates of breast cancer death among black women, diagnosed with the disease,
      irrespective of ER expression, and especially in the first few years following
      diagnosis. Greater emphasis should be placed on identifying the etiology of these
      excess hazards and developing therapeutic strategies to address them.

PMID- 19584329
TI  - The cover. Their audience.

PMID- 19584330
TI  - A piece of my mind. Physician by number.

PMID- 19584328
TI  - Racial disparities in cancer survival among randomized clinical trials patients
      of the Southwest Oncology Group.
AB  - BACKGROUND: Racial disparities in cancer outcomes have been observed in several
      malignancies. However, it is unclear if survival differences persist after
      adjusting for clinical, demographic, and treatment variables. Our objective was
      to determine whether racial disparities in survival exist among patients enrolled
      in consecutive trials conducted by the Southwest Oncology Group (SWOG). METHODS:
      We identified 19 457 adult cancer patients (6676 with breast, 2699 with lung,
      1244 with colon, 1429 with ovarian, and 1843 with prostate cancers; 1291 with
      lymphoma; 2067 with leukemia; and 2208 with multiple myeloma) who were treated on
      35 SWOG randomized phase III clinical trials from October 1, 1974, through
      November 29, 2001. Patients were grouped according to studies of diseases with
      similar histology and stage. Cox regression was used to evaluate the association
      between race and overall survival within each disease site grouping, controlling
      for available prognostic factors plus education and income, which are surrogates
      for socioeconomic status. Median and ten-year overall survival estimates were
      derived by the Kaplan-Meier method. All statistical tests were two-sided.
      RESULTS: Of 19 457 patients registered, 2308 (11.9%, range = 3.9%-21.6%) were
      African American. After adjustment for prognostic factors, African American race
      was associated with increased mortality in patients with early-stage
      premenopausal breast cancer (hazard ratio [HR] for death = 1.41, 95% confidence
      interval [CI] = 1.10 to 1.82; P = .007), early-stage postmenopausal breast cancer
      (HR for death = 1.49, 95% CI = 1.28 to 1.73; P < .001), advanced-stage ovarian
      cancer (HR for death = 1.61, 95% CI = 1.18 to 2.18; P = .002), and advanced-stage
      prostate cancer (HR for death = 1.21, 95% CI = 1.08 to 1.37; P = .001). No
      statistically significant association between race and survival for lung cancer,
      colon cancer, lymphoma, leukemia, or myeloma was observed. Additional adjustments
      for socioeconomic status did not substantially change these observations. Ten
      year (and median) overall survival rates for African American vs all other
      patients were 68% (not reached) vs 77% (not reached), respectively, for early
      stage, premenopausal breast cancer; 52% (10.2 years) vs 62% (13.5 years) for
      early-stage, postmenopausal breast cancer; 13% (1.3 years) vs 17% (2.3 years) for
      advanced ovarian cancer; and 6% (2.2 years) vs 9% (2.7 years) for advanced
      prostate cancer. CONCLUSIONS: African American patients with sex-specific cancers
      had worse survival than white patients, despite enrollment on phase III SWOG
      trials with uniform stage, treatment, and follow-up.

PMID- 19584331
TI  - NIH program to boost pipeline for drugs to treat rare and neglected diseases.

PMID- 19584332
TI  - New study supports lifesaving benefits of implantable defibrillation devices.

PMID- 19584333
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584334
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584335
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584336
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584337
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584338
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584339
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584340
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584341
TI  - Clinical practice guidelines and scientific evidence.

PMID- 19584342
TI  - Treatment for individuals with HIV/AIDS following release from prison.

PMID- 19584343
TI  - Treatment for individuals with HIV/AIDS following release from prison.

PMID- 19584344
TI  - Tubular diskectomy vs conventional microdiskectomy for sciatica: a randomized
      controlled trial.
AB  - CONTEXT: Conventional microdiskectomy is the most frequently performed surgery
      for patients with sciatica due to lumbar disk herniation. Transmuscular tubular
      diskectomy has been introduced to increase the rate of recovery, although
      evidence is lacking of its efficacy. OBJECTIVE: To determine outcomes and time to
      recovery in patients treated with tubular diskectomy compared with conventional
      microdiskectomy. DESIGN, SETTING, AND PATIENTS: The Sciatica Micro-Endoscopic
      Diskectomy randomized controlled trial was conducted among 328 patients aged 18
      to 70 years who had persistent leg pain (>8 weeks) due to lumbar disk herniations
      at 7 general hospitals in The Netherlands from January 2005 to October 2006.
      Patients and observers were blinded during the follow-up, which ended 1 year
      after final enrollment. INTERVENTIONS: Tubular diskectomy (n = 167) vs
      conventional microdiskectomy (n = 161). MAIN OUTCOME MEASURES: The primary
      outcome was functional assessment on the Roland-Morris Disability Questionnaire
      (RDQ) for sciatica (score range: 0-23, with higher scores indicating worse
      functional status) at 8 weeks and 1 year after randomization. Secondary outcomes
      were scores on the visual analog scale for leg pain and back pain (score range: 0
      100 mm) and patient's self-report of recovery (measured on a Likert 7-point
      scale). RESULTS: Based on intention-to-treat analysis, the mean RDQ score during
      the first year after surgery was 6.2 (95% confidence interval [CI], 5.6 to 6.8)
      for tubular diskectomy and 5.4 (95% CI, 4.6 to 6.2) for conventional
      microdiskectomy (between-group mean difference, 0.8; 95% CI, -0.2 to 1.7). At 8
      weeks after surgery, the RDQ mean (SE) score was 5.8 (0.4) for tubular diskectomy
      and 4.9 (0.5) for conventional microdiskectomy (between-group mean difference,
      0.8; 95% CI, -0.4 to 2.1). At 1 year, the RDQ mean (SE) score was 4.7 (0.5) for
      tubular diskectomy and 3.4 (0.5) for conventional microdiskectomy (between-group
      mean difference, 1.3; 95% CI, 0.03 to 2.6) in favor of conventional
      microdiskectomy. On the visual analog scale, the 1-year between-group mean
      difference in improvement was 4.2 mm (95% CI, 0.9 to 7.5 mm) for leg pain and 3.5
      mm (95% CI, 0.1 to 6.9 mm) for back pain in favor of conventional
      microdiskectomy. At 1 year, 107 of 156 patients (69%) assigned to tubular
      diskectomy reported a good recovery vs 120 of 151 patients (79%) assigned to
      conventional microdiskectomy (odds ratio, 0.59 [95% CI, 0.35 to 0.99]; P = .05).
      CONCLUSIONS: Use of tubular diskectomy compared with conventional microdiskectomy
      did not result in a statistically significant improvement in the Roland-Morris
      Disability Questionnaire score. Tubular diskectomy resulted in less favorable
      results for patient self-reported leg pain, back pain, and recovery. TRIAL
      REGISTRATION: isrctn.org Identifier: ISRCTN51857546.

PMID- 19584345
TI  - Effect of reduced-dose schedules with 7-valent pneumococcal conjugate vaccine on
      nasopharyngeal pneumococcal carriage in children: a randomized controlled trial.
AB  - CONTEXT: The effects of reduced-dose schedules of 7-valent pneumococcal conjugate
      vaccine (PCV-7) on pneumococcal carriage in children are largely unknown,
      although highly relevant in the context of subsequent herd effects. OBJECTIVE: To
      examine the effects of a 2-dose and 2 + 1-dose PCV-7 schedule on nasopharyngeal
      pneumococcal carriage in young children compared with controls. DESIGN, SETTING,
      AND PATIENTS: A randomized controlled trial of nasopharyngeal carriage of
      Streptococcus pneumoniae enrolling 1003 healthy newborns and 1 of their parents
      in a general community in The Netherlands, with follow-up to age 24 months and
      conducted between July 7, 2005, and February 14, 2008. INTERVENTION: Infants were
      randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of
      PCV-7 at 2, 4, and 11 months; or no dosage (control group). MAIN OUTCOME MEASURE:
      Vaccine serotype pneumococcal carriage rates in infants in the second year of
      life. RESULTS: At 12 months, vaccine serotype pneumococcal carriage was
      significantly decreased after both PCV-7 schedules, with vaccine serotype
      pneumococcal carriage rates of 25% (95% confidence interval [CI], 20%-30%) and
      20% (95% CI, 16%-25%) in the 2-dose and 2 + 1-dose schedule groups, respectively,
      vs 38% (95% CI, 33%-44%) in the control group (both P < .001). At 18 months, in
      the 2 + 1-dose schedule group, vaccine serotype pneumococcal carriage had further
      decreased to 16% (95% CI, 12%-20%) and, at 24 months, to 14% (95% CI, 11%-18%;
      both P < .001); whereas in the 2-dose schedule group, vaccine serotype
      pneumococcal carriage had remained stable at 18 months (24%; 95% CI, 20%-29%),
      but at 24 months had further decreased to 15% (95% CI, 11%-19%; both P < .001).
      In the control group, vaccine serotype pneumococcal carriage remained around 36%
      to 38% until 24 months. CONCLUSION: Compared with no pneumococcal vaccination, a
      2 + 1-dose and 2-dose schedule of PCV-7 resulted in significant reductions of
      vaccine serotype pneumococcal carriage in the second year of life. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00189020.

PMID- 19584347
TI  - Adiponectin levels and risk of type 2 diabetes: a systematic review and meta
      analysis.
AB  - CONTEXT: The association of obesity with development of type 2 diabetes may be
      partly mediated by altered secretion of adipokines by adipose tissue. Greater
      adiposity down-regulates secretion of adiponectin, an adipokine with anti
      inflammatory and insulin-sensitizing properties. The strength and consistency of
      the relation between plasma adiponectin and risk of type 2 diabetes is unclear.
      OBJECTIVE: To systematically review prospective studies of the association of
      plasma adiponectin levels and risk of type 2 diabetes. DATA SOURCES: A systematic
      search of the MEDLINE, EMBASE, and Science Citation Index Expanded databases
      using adiponectin and diabetes and various synonyms and reference lists of
      retrieved articles up to April 10, 2009. STUDY SELECTION: We included prospective
      studies with plasma adiponectin levels as the exposure and incidence of type 2
      diabetes as the outcome variable. DATA EXTRACTION: Two reviewers independently
      extracted data and assessed study quality. Generalized least-squares trend
      estimation was used to assess dose-response relationships. Pooled relative risks
      and 95% confidence intervals were calculated using random-effects models to
      incorporate between-study variation. RESULTS: Thirteen prospective studies with a
      total of 14 598 participants and 2623 incident cases of type 2 diabetes were
      included in the meta-analysis. Higher adiponectin levels were monotonically
      associated with a lower risk of type 2 diabetes. The relative risk of type 2
      diabetes was 0.72 (95% confidence interval, 0.67-0.78) per 1-log microg/mL
      increment in adiponectin levels. This inverse association was consistently
      observed in whites, East Asians, Asian Indians, African Americans, and Native
      Americans and did not differ by adiponectin assay, method of diabetes
      ascertainment, duration of follow-up, or proportion of women. The estimated
      absolute risk difference (cases per 1000 person-years) per 1-log microg/mL
      increment in adiponectin levels was 3.9 for elderly Americans and 30.8 for
      Americans with impaired glucose tolerance. CONCLUSION: Higher adiponectin levels
      are associated with a lower risk of type 2 diabetes across diverse populations,
      consistent with a dose-response relationship.

PMID- 19584348
TI  - FDA performance goals for approving drugs and biologics.

PMID- 19584349
TI  - The need for improved access to FDA reviews.

PMID- 19584346
TI  - Genetic variants associated with cardiac structure and function: a meta-analysis
      and replication of genome-wide association data.
AB  - CONTEXT: Echocardiographic measures of left ventricular (LV) structure and
      function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To
      identify common genetic variants associated with cardiac structure and function
      by conducting a meta-analysis of genome-wide association data in 5 population
      based cohort studies (stage 1) with replication (stage 2) in 2 other community
      based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community
      based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals
      of European ancestry; 55% women, aged 26-95 years; examinations between 1978
      2008), we estimated the association between approximately 2.5 million single
      nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and
      echocardiographic traits. In stage 2, SNPs significantly associated with traits
      in stage 1 were tested for association in 2 other cohorts (n = 4094 people of
      European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to
      indicate genome-wide significance, we performed an inverse variance-weighted
      fixed-effects meta-analysis of genome-wide association data from each cohort.
      MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions,
      wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS:
      In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1
      each with LV internal dimensions and systolic dysfunction, 3 each with LV mass
      and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated
      (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait
      variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size,
      explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci
      harboring common variants that were associated with variation in LV diastolic
      dimensions and aortic root size, but such findings explained a very small
      proportion of variance. Further studies are required to replicate these findings,
      identify the causal variants at or near these loci, characterize their functional
      significance, and determine whether they are related to overt cardiovascular
      disease.

PMID- 19584350
TI  - Possible outcomes of comparative effectiveness research.

PMID- 19584351
TI  - Beyond information: exploring patients' preferences.

PMID- 19584352
TI  - Resolving unreported conflicts of interest.

PMID- 19584353
TI  - JAMA patient page. Sciatica.

PMID- 19584354
TI  - Caspase-8 for outer harmony.
AB  - The epidermis is part of the innate immune system and represents the first line
      of defense against external insults. It must continuously replace differentiated
      or damaged keratinocytes, and this is maintained through a multilayered structure
      and a dynamic equilibrium between proliferation of stem cells and transit
      amplifying cells in the basal layer and differentiation in suprabasal layers. At
      the surface of the epidermis, keratinocytes die by a specific and well
      orchestrated terminal differentiation process, and the resulting dead corneocytes
      play an essential function as the first barrier against the environment. New
      evidence demonstrates that keratinocyte-specific ablation of the apoptotic
      caspase-8 in mice destroys the balance in the epidermis. Although differentiation
      in the outermost epidermal layers of these mice is normal, the mice suffer from
      strong cutaneous inflammation because of enhanced production and secretion of the
      proinflammatory cytokine pro-interleukin-1alpha.

PMID- 19584357
TI  - Scotties put editor in doghouse.

PMID- 19584356
TI  - Declines in levels of hyperpolarization-activated cation (HCN) channels in the
      rat ovary after cisplatin exposure.
AB  - The distribution of the 4 hyperpolarization-activated cation (hyperpolarization
      activated, cyclic nucleotide-gated [HCN]) channels (HCN1-4), channels associated
      with rhythmic electrical bursting, varies in the different cells of the ovary.
      Cisplatin is a broadly used chemotherapeutic agent that results in ovarian
      damage. The objective of this study was to test the hypothesis that cisplatin
      treatment will affect expression of the ovarian HCN channels. Adult female
      Sprague-Dawley rats were dosed with saline, 4.5 mg/kg cisplatin, or 6.0 mg/kg
      cisplatin as 2 weekly injections and then were killed 5 days after the second
      cisplatin dose. The ovaries were studied for HCN1-4 using semiquantitative H
      score immunohistochemical analysis and using Western blot analysis. By
      immunohistochemistry, for HCN4, the oocyte-specific staining declined after
      cisplatin treatment (P < .001). There was a decline in HCN2 intensity after
      cisplatin in the antral granulosa cells (P < .05) and thecal cells (P < .05).
      There were no differences found for the immunohistochemical HCN1 and HCN3 H
      scores after cisplatin. The Western blot analysis revealed that there was a
      decline in HCN3 levels after cisplatin exposure (P < .05). For HCN1 and HCN2,
      there was no change in the total ovarian protein levels after cisplatin.
      Treatment in vivo with cisplatin resulted in decline in the levels of the HCN
      channels in the rat ovary, with oocytes, antral cells, and thecal cells being
      specifically affected.

PMID- 19584358
TI  - Radiologic science educator stress and burnout.
AB  - PURPOSE: To examine the perceived level of occupational stress and burnout of
      radiologic science educators. METHODS: The Maslach Burnout Inventory (MBI) with
      health status and demographic survey was sent by e-mail to 241 members of the
      Association of Educators in Imaging and Radiologic Sciences Inc. The survey
      yielded a 62% response rate. Independent sample t-tests, regression analysis and
      one-way ANOVAs were used to compare data. RESULTS: Results indicated average
      levels for radiologic science educator feelings of emotional exhaustion, low
      levels for their feelings of depersonalization and average levels for their
      feelings of personal accomplishment. A statistically significant result was found
      between all 3 subscales of the MBI and the reported health status. CONCLUSION:
      This research study may help raise awareness of stress and burnout and their
      relationship to the health of radiologic science educators.

PMID- 19584359
TI  - Educational program emergency planning.
AB  - BACKGROUND: Tragic university shootings have prompted administrators of higher
      education institutions to re-evaluate their emergency preparedness plans and take
      appropriate measures for preventing and responding to emergencies. OBJECTIVE: To
      review the literature and identify key components needed to prevent shootings at
      higher education institutions in the United States, and in particular,
      institutions housing radiologic science programs. METHODS: Twenty-eight emergency
      preparedness plans were retrieved electronically and reviewed from a convenience
      sample of accredited radiologic science programs provided by the Joint Review
      Committee on Education in Radiologic Technology Web site. RESULTS: The review of
      the 28 emergency preparedness plans confirmed that most colleges are prepared for
      basic emergencies, but lack the key components needed to successfully address
      mass-casualty events. Only 5 (18%) of the 28 institutions addressed policies
      concerning school shootings.

PMID- 19584355
TI  - Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and
      ubiquitylation by pVHL.
AB  - Agonist-induced ubiquitylation and degradation of heterotrimeric guanine
      nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play an
      essential role in surface receptor homeostasis, thereby tuning many physiological
      processes. Although beta-arrestin and affiliated E3 ligases mediate agonist
      stimulated lysosomal degradation of the beta(2)-adrenergic receptor (beta(2)AR),
      a prototypic GPCR, the molecular cues that mark receptors for ubiquitylation and
      the regulation of receptor degradation by the proteasome remain poorly
      understood. We show that the von Hippel-Lindau tumor suppressor protein (pVHL)-E3
      ligase complex, known for its regulation of hypoxia-inducible factor (HIF)
      proteins, interacts with and ubiquitylates the beta(2)AR, thereby decreasing
      receptor abundance. We further show that the interaction of pVHL with beta(2)AR
      is dependent on proline hydroxylation (proline-382 and -395) and that the
      dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous
      beta(2)AR prolyl hydroxylase. Under hypoxic conditions, receptor hydroxylation
      and subsequent ubiquitylation decrease dramatically, thus attenuating receptor
      degradation and down-regulation. Notably, in both cells and tissue, the abundance
      of endogenous beta(2)AR is shown to reflect constitutive turnover by EGLN3 and
      pVHL. Our findings provide insight into GPCR regulation, broaden the functional
      scope of prolyl hydroxylation, and expand our understanding of the cellular
      response to hypoxia.

PMID- 19584360
TI  - Using medical imaging to decipher autism.
AB  - A steady stream of news stories reflects a growing focus on research concerning
      autism. Increasingly, scientists endeavor to identify the possible causes of the
      disorder, to explore the differences between autistic and neurotypical brains and
      to emphasize the need for accurate, timely diagnosis and early intervention.
      Several controversies surround the puzzle that is autism, including what culprits
      might be responsible for so many newly diagnosed cases each year. Fortunately,
      exciting advances in imaging technology and brain research promise a greater
      understanding of the disorder and extend much-needed hope to families and
      professionals facing the challenges of autism. This article is a Directed
      Reading. Your access to Directed Reading quizzes for continuing education credit
      is determined by your area of interest. For access to other quizzes, go to
      www.asrt.org/store.

PMID- 19584361
TI  - Pharmacology in radiology.
AB  - Radiologic technologists need a basic understanding of pharmacology principles.
      This is particularly true during radiographic examinations involving contrast
      media administration. A fundamental knowledge of pharmacodynamics and
      pharmacokinetics can help radiologic technologists and radiologist assistants
      better understand how medications act, possible adverse reactions medications can
      cause in patients and the principles of drug administration. This article is a
      Directed Reading. Your access to Directed Reading quizzes for continuing
      education credit is determined by your area of interest. For access to other
      quizzes, go to www.asrt.org/store.

PMID- 19584362
TI  - Contrast-enhanced ultrasound.
AB  - Throughout Europe and Asia, microsphere contrast agents called microbubbles are
      revolutionizing traditional ultrasonography, dramatically improving the precision
      of diagnostic sonograms and expanding the clinical scope of a widely used imaging
      modality. Microbubbles improve visualization of blood flow, the cardiovascular
      system and the perfusion of blood into vital organs, particularly the liver,
      making contrast-enhanced ultrasound (CEUS) competitive with other diagnostic
      imaging modalities for these applications. This article reviews the concepts,
      principles, applications and techniques of CEUS and describes changing regulatory
      views regarding contraindications. Emerging therapeutic applications also are
      discussed. This article is a Directed Reading. Your access to Directed Reading
      quizzes for continuing education credit is determined by your area of interest.
      For access to other quizzes, go to www.asrt.org/store.

PMID- 19584363
TI  - Scanning protocols improve efficiency.

PMID- 19584364
TI  - Deficit reduction act affects staffing.

PMID- 19584365
TI  - What type of leader are you?

PMID- 19584366
TI  - Bomb survivors and radiation protection.

PMID- 19584367
TI  - Evaluating resources.

PMID- 19584368
TI  - Spot the problem here?

PMID- 19584369
TI  - 7-tesla small animal MR imaging.

PMID- 19584370
TI  - Redesigning online course delivery.

PMID- 19584371
TI  - Bone densitometry.

PMID- 19584372
TI  - Patient satisfaction and physician productivity: complementary or mutually
      exclusive?
AB  - Motivating physicians to increase productivity and maximize patient satisfaction
      may result in conflicted behavior, raising questions about whether one must be
      sacrificed for the other. To determine if high satisfaction (measured by Press
      Ganey patient satisfaction survey) can be achieved while maintaining high
      productivity (measured in McGladrey relative value units, MRVU), longitudinal
      data collected from January 2002 to July 2004 were modeled using repeated
      measures regression. A total of 136 000 patient-completed satisfaction
      questionnaires evaluating 417 physicians were collected for analysis. Patient
      confidence (positively correlated; P = .001) and physician/patient time
      (inversely correlated; P = .001) were associated with higher physician
      productivity. Increases in MRVU were associated with decreases in patient
      perceptions of time with the physician (P = .003). The relationships between
      patient satisfaction and physician productivity were relatively small, suggesting
      that they are not necessarily incompatible and that both can be improved
      simultaneously.

PMID- 19584373
TI  - Implementation of the National Surgical Quality Improvement Program: critical
      steps to success for surgeons and hospitals.
AB  - The National Surgical Quality Improvement Program (NSQIP), as administered by the
      American College of Surgeons, became available to private sector hospitals across
      the United States in 2004. The program works to improve surgical outcomes by
      providing high-quality, risk-adjusted data to surgeons at a given hospital to
      stimulate discussion and define target areas for improvement. Although the NSQIP
      began in the early 1990s with Veterans Administration hospitals and expanded to
      private sector hospitals nearly 5 years ago, the "how to" process for NSQIP
      implementation has been left to individual institutions to manage on their own.
      The NSQIP was instituted at a large tertiary hospital in 2005, identifying
      through experience 12 critical steps to help surgeons and hospitals implement the
      NSQIP.

PMID- 19584375
TI  - Quality: the Mayo Clinic approach.
AB  - Developing highly reliable care for patients requires changes in some traditional
      beliefs of medical practice, an evolution toward a "system" of health care, the
      disciplined application of scientific principles, modifications in the way all
      future providers are trained, and a fundamental understanding by leadership that
      quality must become a business strategy and core work, not an expense or
      regulatory requirement. Quality at Mayo is defined as a composite of outcomes,
      safety, and service. A 4-part strategic construct focusing on Culture,
      Infrastructure, Engineering, and Execution has been developed to guide
      improvement activities and to ensure a comprehensive approach to better patient
      care. The Mayo Clinic experience has led to a greater understanding of the
      leadership commitment, organizational challenges, and the breadth of initiatives
      necessary to achieve highly reliable care.

PMID- 19584374
TI  - Assessing surgical quality using administrative and clinical data sets: a direct
      comparison of the University HealthSystem Consortium Clinical Database and the
      National Surgical Quality Improvement Program data set.
AB  - The use of "clinical" versus "administrative" data sets for health care quality
      assessment continues to be debated. This study directly compares the University
      HealthSystem Consortium Clinical Database (UHC CDB) and the National Surgical
      Quality Improvement Program (NSQIP) in terms of their assessment of complications
      and death for 26 322 surgery patients using analyses of variance, correlation,
      and multivariable logistic regression. The NSQIP had more variables with
      significant correlation with outcomes. The NSQIP was better at predicting death
      (c-index 0.94 vs 0.90, P < .05) and complications (c-index 0.78 vs 0.76, P =
      .07), especially for higher risk patients. The UHC CDB missed and misclassified
      several major complications. The data sets are similar in their explanatory power
      relative to outcomes, but the clinical data set is better, particularly at
      identifying higher risk patients and specific complications. It should prove more
      useful for initiating and monitoring clinical process improvements because of
      more clinically relevant variables.

PMID- 19584376
TI  - Medicare's new hospital payment rule: limitations and unintended consequences.

PMID- 19584377
TI  - Pay-for-performance (of) advance directives.

PMID- 19584378
TI  - Risperidone treatment of an adolescent with severe posttraumatic stress disorder.

PMID- 19584379
TI  - Dapagliflozin for the treatment of type 2 diabetes.
AB  - OBJECTIVE: To review the literature and describe the pharmacology,
      pharmacokinetics, clinical safety, and efficacy of dapagliflozin, a compound
      currently in Phase 3 clinical trials. DATA SOURCES: A search of the literature
      was conducted via MEDLINE (1995-March 2009) and ClinicalTrials.gov using the
      search terms dapagliflozin, SGLT2 inhibitor, sodium-glucose co-transport
      inhibition, and renal glucose reabsorption inhibition. Bibliographies of
      identified articles were also used to identify useful references. STUDY SELECTION
      AND DATA EXTRACTION: All English-language reports evaluating dapagliflozin were
      included in this review, including abstracts and scientific presentations. DATA
      SYNTHESIS: Due to the increasing prevalence of type 2 diabetes, suboptimal
      management of the associated hyperglycemia, morbidity and mortality associated
      with the disease, and the limitations of currently available therapies, novel
      therapeutic strategies are needed for its treatment. Dapagliflozin represents the
      first selective, sodium-glucose cotransporter 2 inhibitor that functions by
      regulating renal glucose reabsorption. Clinical trial data are limited, but
      available evidence supports clinically significant reductions in fasting plasma
      glucose, postprandial plasma glucose, hemoglobin A(1c), and body weight with this
      agent. In addition, dapagliflozin has demonstrated excellent tolerability with
      safety data demonstrated in both Phase 1 and Phase 2 studies. CONCLUSIONS:
      Dapagliflozin represents the first in a new class of drugs that may represent a
      promising new option in the treatment of type 2 diabetes. Results of ongoing
      Phase 3 clinical trials are necessary to demonstrate efficacy and safety of this
      agent across various patient populations and clinical scenarios.

PMID- 19584380
TI  - Prefilter bivalirudin for preventing hemofilter occlusion in continuous renal
      replacement therapy.
AB  - OBJECTIVE: To describe a case of successful bivalirudin use as a prefilter
      anticoagulant in continuous venovenous hemofiltration (CVVH). CASE SUMMARY: A 30
      year-old male was brought to the hospital by ambulance with an anterior
      communicating artery subarachnoid hemorrhage, signs of intraparenchymal
      hemorrhage, and hydrocephalus. During the patient's complicated hospital course,
      he developed acute renal failure requiring CVVH, as well as hepatic insufficiency
      (Child-Pugh class B). Unfractionated heparin was used as a prefilter
      anticoagulant. After he had a positive heparin-induced thrombocytopenia (HIT)
      antibody test, prefilter heparin was discontinued in favor of bivalirudin. Filter
      survival and systemic activated partial thromboplastin time (aPTT) values were
      compared between prefilter heparin (n = 5) and bivalirudin (n = 4). Filter
      survival was similar (median 26 h with heparin vs 37 h with bivalirudin; p =
      0.52). Prefilter bivalirudin 1-2.5 mg/hour (0.009-0.023 mg/kg/h) was effective in
      maintaining systemic aPTTs that were 1-1.4 times the reference range. Serotonin
      release assay and subsequent HIT antibodies were negative. The patient's renal
      function improved and CVVH was discontinued. DISCUSSION: Critically ill patients
      requiring CVVH often need regional or systemic anticoagulation to prevent filter
      occlusion. In some patient populations, such as those with HIT or liver failure,
      prefilter heparin and regional citrate, respectively, may not be options.
      Alternative anticoagulants may be needed to avoid complications of frequent
      filter occlusions. The direct thrombin inhibitors (DTIs) lepirudin and argatroban
      have been used to maintain hemofilter patency, in small studies. Bivalirudin may
      have pharmacokinetic advantages over other DTIs when used in patients with
      hepatic and renal impairment. In our patient, bivalirudin provided a safe
      alternative to heparin therapy and was effective in maintaining hemofilter
      patency during CVVH. CONCLUSIONS: Prefilter bivalirudin may be an option to
      prevent filter occlusion in patients requiring continuous renal replacement
      therapy. Future studies are needed to validate the safety and efficacy of
      bivalirudin as a prefilter anticoagulant.

PMID- 19584381
TI  - Application of STOPP and START criteria: interrater reliability among
      pharmacists.
AB  - BACKGROUND: Inappropriate prescribing is a well-documented problem in older
      people. The new screening tools, STOPP (Screening Tool of Older Peoples'
      Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment)
      have been formulated to identify potentially inappropriate medications (PIMs) and
      potential errors of omissions (PEOs) in older patients. Consistent, reliable
      application of STOPP and START is essential for the screening tools to be used
      effectively by pharmacists. OBJECTIVE: To determine the interrater reliability
      among a group of clinical pharmacists in applying the STOPP and START criteria to
      elderly patients' records. METHODS: Ten pharmacists (5 hospital pharmacists, 5
      community pharmacists) were given 20 patient profiles containing details
      including the patients' age and sex, current medications, current diagnoses,
      relevant medical histories, biochemical data, and estimated glomerular filtration
      rate. Each pharmacist applied the STOPP and START criteria to each patient
      record. The PIMs and PEOs identified by each pharmacist were compared with those
      of 2 academic pharmacists who were highly familiar with the application of STOPP
      and START. An interrater reliability analysis using the kappa statistic (chance
      corrected measure of agreement) was performed to determine consistency between
      pharmacists. RESULTS: The median kappa coefficients for hospital pharmacists and
      community pharmacists compared with the academic pharmacists for STOPP were 0.89
      and 0.88, respectively, while those for START were 0.91 and 0.90, respectively.
      CONCLUSIONS: Interrater reliability of STOPP and START tools between pharmacists
      working in different sectors is good. Pharmacists working in both hospitals and
      in the community can use STOPP and START reliably during their everyday practice
      to identify PIMs and PEOs in older patients.

PMID- 19584382
TI  - Acquired Fanconi syndrome after treatment with capecitabine, irinotecan, and
      bevacizumab.
AB  - OBJECTIVE: To describe a case of acquired Fanconi syndrome after treatment with
      capecitabine, irinotecan, and bevacizumab. CASE SUMMARY: A 77-year-old female
      with metastatic colon cancer presented with vomiting and diarrhea. The patient
      had been diagnosed with stage IIIC (T3, N2, M0) colon cancer 18 months earlier
      and was initially treated with FOLFOX6 (regimen of oxaliplatin, fluorouracil, and
      leucovorin) after her hemicolectomy. She was switched to a
      capecitabine/oxaliplatin regimen after 4 cycles due to central access problems.
      She did well until 10 months after her cancer diagnosis, when metastasis was
      discovered. She was started on reduced doses of capecitabine, irinotecan, and
      bevacizumab. After her eleventh cycle, she presented to the hospital with the
      above symptoms. Laboratory test results showed hypokalemia, hypocalcemia,
      hypophosphatemia, and hypouricemia. The patient had not been started on any new
      medications other than chemotherapy for over 1 year. The electrolyte derangements
      were new, since the patient had laboratory values checked every 3 weeks. Despite
      daily intravenous replacements, the electrolyte abnormalities persisted.
      Laboratory evaluations demonstrated the presence of euglycemic glucosuria and a
      high fractional excretion of phosphorus in the setting of hypophosphatemia.
      Fanconi syndrome was confirmed by demonstration of aminoaciduria. DISCUSSION:
      Fanconi syndrome is a disorder characterized by proximal tubular dysfunction
      resulting in electrolyte wasting. In the acquired form, medications and multiple
      myeloma are the most common causes. Based on the Naranjo probability scale, a
      drug was the probable cause of Fanconi syndrome in our patient. However, because
      multiple drugs were involved, it was not possible to determine which one was the
      culprit. CONCLUSIONS: This is the first case of Fanconi syndrome reported after
      the administration of capecitabine, irinotecan, and bevacizumab. More studies are
      needed to confirm this association.

PMID- 19584383
TI  - Ordering off the menu: assessing compliance with a nonformulary medication
      policy.
AB  - BACKGROUND: Use of nonformulary medications (NFMs) may create added costs and
      potential safety issues. Institutional policies can support compliance with
      formulary systems and address these issues. However, periodic review is needed to
      assess the effectiveness of NFM policies. OBJECTIVE: To evaluate NFM use at a
      large university medical center and assess for compliance with the established
      policy as well as for prescribing errors, procurement procedures, and delivery
      times. METHODS: All new medication orders entered as NFM in the computerized
      order entry system during a 6-week period were evaluated and followed until
      administration of the first NFM dose. Orders were categorized as NFMs, formulary
      medications (FMs), or the patient's own medications. Each order was evaluated to
      determine the prescriber, service and location of the patient, and any
      prescribing errors. Additional information, such as the indication, location
      where the medication was obtained, and the delivery time, was obtained through
      patient chart review and the pharmacist intervention database. RESULTS: A total
      of 237 orders were entered as nonformulary; 72 (30%) were FMs and 165 (70%) were
      NFMs. Of the 165 NFM orders, 71 (43%) were orders for the patient's own
      medication. Of the remaining 94 NFMs, only 39% met the institution's established
      policy criteria. Overall, 28% of all orders entered as nonformulary had a
      prescribing error. Of these, 49% were incorrect dosages and 33% were misspelled
      orders. Seventy percent of NFMs were obtained from the institution's standard
      locations. The institution's nonformulary turnaround time was achieved with 96%
      of NFMs. CONCLUSIONS: The majority of NFM orders did not meet the institution's
      established criteria and these orders frequently contained prescribing errors.
      Routine assessment of NFM use and policy compliance can present opportunities for
      improvement.

PMID- 19584384
TI  - Safety and clinical outcomes when utilizing high-dose (> or =8 mg/kg) daptomycin
      therapy.
AB  - BACKGROUND: Daptomycin is approved for the treatment of skin and skin-structure
      infections (4 mg/kg) and Staphylococcus aureus bacteremia, including right-sided
      endocarditis (6 mg/kg). In vitro and animal studies have reported increased
      activity with increased daptomycin doses. There are limited clinical data on use
      of daptomycin at doses greater than 6 mg/kg. OBJECTIVE: To evaluate the safety
      and efficacy of higher doses (> or =8 mg/kg) of daptomycin when administered for
      a variety of gram-positive infections. METHODS: Data were collected
      retrospectively as part of an ongoing registry (the Cubicin Outcomes Registry and
      Experience database) for the 2005-2007 program years. For the purpose of this
      study, the safety and efficacy of daptomycin were evaluated in patients who
      received doses of 8 mg/kg or higher. RESULTS: Ninety-four (2.6%) of 3617 patients
      received daptomycin doses of 8 mg/kg or higher; 18 (19%) of those patients
      received doses of 10 mg/kg or higher. The most common infections were bacteremia
      (30/94), skin and skin-structure infections (22/94), and endocarditis (15/94).
      The most common pathogens were Enterococcus spp. (37/94; 57% vancomycin
      resistant) and S. aureus (28/94; 68% methicillin-resistant). Fifty-one percent of
      the patients were male, 39% were aged 66 years or older, 27% had an initial
      creatinine clearance less than 30 mL/min, and 17% were on dialysis. The median
      duration of daptomycin therapy was 15 days (minimum 1, maximum 90). Six (6.4%) of
      the 94 patients experienced 1 or more adverse events or abnormal laboratory value
      changes possibly related to daptomycin; in 2 (2.1%) of the 94 patients,
      daptomycin was discontinued due to treatment-related adverse events. Seventy-four
      (79%) patients were considered evaluable for efficacy. The overall clinical
      success rate was 89% (bacteremia, 91%; skin and skin-structure infections, 88%;
      endocarditis, 67%). CONCLUSIONS: Daptomycin was well tolerated and effective at
      doses of 8 mg/kg or higher in patients with gram-positive infections. Further
      prospective and comparative studies of daptomycin at doses greater than 6 mg/kg
      are warranted.

PMID- 19584385
TI  - Clevidipine: an ultra short-acting calcium channel antagonist for acute
      hypertension.
AB  - OBJECTIVE: To review the safety, efficacy, and pharmacologic characteristics of
      clevidipine, a new ultra short-acting intravenous antihypertensive agent for the
      treatment of moderate-to-severe hypertension. DATA SOURCES: A literature search
      was conducted through MEDLINE (1966-March 2009), International Pharmaceutical
      Abstracts (1970-March 2009), and EMBASE (1988-March 2009) using the search terms
      clevidipine, H324/38, hypertension, and hypertensive crisis. STUDY SELECTION AND
      DATA EXTRACTION: Available studies, abstracts, and review articles published in
      English that evaluated the pharmacology, pharmacokinetics, safety, and clinical
      efficacy of clevidipine were reviewed and critically evaluated. DATA SYNTHESIS:
      Clevidipine is a new third-generation dihydropyridine calcium-channel blocker
      available for intravenous management of moderate-to-severe hypertension.
      Clevidipine is an ultra short-acting, selective arteriolar vasodilator that acts
      similar to other L-type dihydropyridine calcium-channel blockers by inhibiting
      influx of extracellular calcium into the vascular smooth muscle. Its safety and
      efficacy have been primarily evaluated in the perioperative setting in patients
      undergoing cardiac surgery requiring management of elevated blood pressure. In
      comparison to most other intravenous antihypertensives, clevidipine has a rapid
      onset of action, is ultra short-acting, easily titratable with a predictable dose
      response, and is void of drug-drug interactions and need for dose adjustment in
      patients with hepatic or renal insufficiency, thus making it a valuable
      antihypertensive in both the intraoperative and critical care settings. In
      clinical trials, clevidipine was well tolerated at infusion rates from 2-32 mg
      per hour, for up to 72 hours. CONCLUSIONS: Clevidipine is the first intravenous
      antihypertensive approved by the Food and Drug Administration in nearly a decade.
      Based on available published clinical trials, clevidipine appears to be safe and
      effective in the acute management of moderate-to-severe elevations in blood
      pressure and a viable alternative to other agents such as nitroglycerin, sodium
      nitroprusside, and nicardipine.

PMID- 19584386
TI  - Continuous-infusion beta-lactam antibiotics during continuous venovenous
      hemofiltration for the treatment of resistant gram-negative bacteria.
AB  - OBJECTIVE: To describe the rationale, principles, and dosage calculations for
      continuous-infusion beta-lactam antibiotics to treat multidrug-resistant bacteria
      in patients undergoing continuous venovenous hemofiltration (CVVH). DATA SOURCES:
      A MEDLINE search (1968-November 2008) of the English-language literature was
      performed using the terms continuous infusion and Pseudomonas or Acinetobacter;
      hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal
      replacement therapy or pharmacokinetics; and terms describing different beta
      lactam antibiotics. STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and
      human studies were evaluated that used continuous-infusion beta-lactam
      antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii
      infections. Studies were reviewed that described the pharmacokinetics of beta
      lactam antibiotics during CVVH as well as other modalities of continuous renal
      replacement therapy. DATA SYNTHESIS: Continuous infusion of beta-lactam
      antibiotics, maintaining drug concentrations 4-5 times higher than the minimum
      inhibitory concentration, is a promising approach for managing infections caused
      by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy
      is made difficult by the occurrence of acute renal failure and the need for renal
      replacement therapy. Case series and pharmacokinetic properties indicate that
      several beta-lactam antimicrobials that have been studied for continuous
      infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic
      acid, and tazobactam, are significantly cleared by hemofiltration. Methodology
      and formulas are provided that allow practitioners to calculate dosage regimens
      and reach target drug concentrations for continuous beta-lactam antibiotic
      infusions during CVVH based on a literature review, pharmacokinetic principles,
      and our experience at the National Institutes of Health Clinical Center.
      CONCLUSIONS: Continuous infusion of beta-lactam antibiotics may be a useful
      treatment strategy for multidrug-resistant gram-negative infections in the
      intensive care unit. Well-established pharmacokinetic and pharmacodynamic
      principles can be used to safely reach and maintain steady-state target
      concentrations of beta-lactam antibiotics in critical illness complicated by
      acute renal failure requiring CVVH.

PMID- 19584387
TI  - Medication adherence and its effect on relapse among patients discharged from a
      Veterans Affairs posttraumatic stress disorder treatment program.
AB  - BACKGROUND: Clinical outcomes in patients with posttraumatic stress disorder
      (PTSD) can be affected by several factors, including medication adherence. PTSD
      is associated with an increased likelihood of missed appointments, medication
      underuse or abuse, and treatment nonadherence. OBJECTIVE: To evaluate medication
      adherence and its effect on relapse following discharge of veterans from a PTSD
      residential rehabilitation program (PRRP). METHODS: A retrospective evaluation of
      drug adherence and relapse in the 12 months following discharge of patients from
      a PRRP was performed. All veterans who were discharged from January 1, 2005, to
      December 31, 2006, and were receiving antidepressant therapy were included.
      Adherence to antidepressant therapy was assessed by electronic prescription
      claims and defined as a medication possession ratio of at least 0.8 in the year
      following discharge. Relapse was defined as a hospitalization for psychiatric
      symptomatology. Predictive factors of adherence were also explored. RESULTS:
      Twenty-eight of the 82 (34%) veterans included in our study were adherent to
      medication during the 12 months following discharge. Seventeen (20.7%) veterans
      were rehospitalized for psychiatric symptoms, but nonadherence was not
      significantly associated with relapse (p = 0.91). The total number of drugs that
      a veteran received was related to adherence; patients who had a higher median
      number of medications were more adherent (p = 0.014). Age, comorbid substance
      abuse, combat service, and service connection were not associated with drug
      adherence. CONCLUSIONS: The majority of patients who were discharged from a
      residential PTSD treatment program were nonadherent to antidepressant drug
      therapy. One in 5 veterans with PTSD was rehospitalized within 1 year; however,
      medication adherence did not affect this outcome.

PMID- 19584388
TI  - An open-label study of mirtazapine as treatment for combat-related PTSD.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is common among war veterans.
      Antidepressants are effective in reducing symptoms and associated disability for
      some patients. OBJECTIVE: To assess the effectiveness of mirtazapine for combat
      related PTSD among veterans treated in an Australian hospital. METHODS: This open
      label prospective study assessed the effectiveness of mirtazapine as empirical
      treatment for combat-related PTSD. The initial dose was 15 mg at night, titrated
      against response to 15-45 mg. PTSD symptoms were assessed using the Mississippi
      Scale for Combat-Related Posttraumatic Stress Disorder and the Clinician
      Administered PTSD Scale (CAPS). Subjects also completed the Hospital Anxiety and
      Depression Scale (HADS). Body weight and biochemical assessments, including
      fasting blood glucose (FBG), total serum cholesterol, and serum triglycerides,
      were also measured. Baseline measurements were repeated after 12 weeks. RESULTS:
      During the 18-month recruitment phase, 17 subjects were enrolled and 13 completed
      the protocol. The CAPS measurement decreased from a mean pretreatment score of
      87.5 to 64.4 (p = 0.01). In 4 cases, the CAPS score decreased to below the
      diagnostic cut-point, consistent with a remission of PTSD. The Mississippi scale
      measurement decreased from a mean pretreatment score of 126.6 to 115.5 (p <
      0.01). The mean HADS anxiety score decreased from 15.6 +/- 4.2 to 13.5 +/- 5.6 (p
      = 0.016), although the proportion of subjects with scores above the diagnostic
      cut-point remained high. The mean HADS depression score at baseline was not
      significantly different from the postintervention score. One subject had a
      postintervention FBG of 155 mg/dL (consistent with diabetes mellitus), which was
      increased from the baseline level of 83 mg/dL. All subjects experienced an
      increase in body weight. One subject had an increase in body weight of 8.75 kg
      (8.4%) from baseline. CONCLUSIONS: Although small and with methodological
      limitations, this study suggests that mirtazapine is an effective treatment for
      combat-related PTSD. Additional research incorporating an appropriately powered,
      double-blind, placebo-controlled study design is required.

PMID- 19584389
TI  - The epothilones: how pharmacology relates to clinical utility.
AB  - OBJECTIVE: To review the pharmacologic properties of a novel class of
      chemotherapeutic agents, the epothilones, and to summarize findings from recent
      clinical trials investigating the various epothilones in cancer therapy. DATA
      SOURCES: Literature searches were conducted using MEDLINE, PubMed, and the
      abstract search engines for the American Society of Clinical Oncology and
      American Association for Cancer Research annual meetings (all searches through
      November 2008). Primary search terms included epothilone, BMS-247550,
      ixabepilone, EPO906, patupilone, sagopilone, and ZK-EPO. STUDY SELECTION AND DATA
      EXTRACTION: Publications were given priority for inclusion if they discussed
      structural or pharmacologic properties of the epothilones as a class or if they
      included preclinical or clinical data for epothilones currently in clinical
      development. DATA SYNTHESIS: The epothilones are a novel class of microtubule
      stabilizing agents (MSAs). Epothilones are structurally and pharmacologically
      distinct from taxanes, but the exact ways in which the pharmacophores of the 2
      classes differ has not been firmly established. A number of natural,
      semisynthetic, and fully synthetic epothilones are in various stages of clinical
      development. These agents differ from each other and from existing MSAs; these
      differences influence potency, stability, and solubility. Ixabepilone is
      currently approved to treat multidrug-resistant metastatic breast cancer and has
      demonstrated efficacy in earlier stages of breast cancer and in several other
      tumor types. Patupilone and sagopilone are currently under clinical investigation
      and have each shown promise in a number of treatment settings and tumor types.
      All 3 agents appear to be associated with manageable toxicities, but no class
      wide toxicity profile exists for the epothilones and dose-limiting toxicities
      differ among the agents. CONCLUSIONS: The epothilones have demonstrated
      significant potential for addressing the growing therapeutic challenge of taxane
      resistance, and the ever-increasing pool of information regarding structure
      activity relationships of these MSAs will help to optimize microtubule-targeted
      chemotherapy.

PMID- 19584390
TI  - Current concepts in vascular cognitive impairment and pharmacotherapeutic
      implications.
AB  - OBJECTIVE: To review evolution of the vascular cognitive impairment (VCI)
      construct, including diagnosis, pharmacotherapeutic implications, and address
      challenges that will shape future developments. DATA SOURCES: Literature
      retrieval was accessed through PubMed, from 1966 to December 2008, using the
      terms vascular cognitive impairment, vascular dementia, post-stroke dementia,
      vascular cognitive disorder, mild cognitive impairment, criteria, disease
      progression, outcomes, treatment, prevention, biomarkers, and neuroimaging. STUDY
      SELECTION AND DATA EXTRACTION: All articles in published English identified from
      the data sources were evaluated for inclusion. Regarding pharmacotherapy,
      prospective double-blind, placebo-controlled studies were included as well as
      extensions or relevant post hoc analyses. DATA SYNTHESIS: In the 1970s, "senile
      dementia due to hardening of the arteries" was used to describe dementia due to
      vascular causes. This was a narrow view of what is now known to be a common form
      of cognitive impairment in older people. Multiple infarct dementia (MID) was
      first proposed to describe dementia attributable to multiple cerebral infarcts,
      followed by the vascular dementia (VaD) construct, itself meant to be an
      improvement over MID. The VaD construct had limitations, not the least of which
      was that, by the time a patient was diagnosed with VaD, the opportunity for
      prevention was lost. Thus arose the concept of VCI, representing a group of
      heterogeneous disorders that share presumed vascular causes. The importance of
      VCI is centered on the fact that vascular risk factors are treatable, and thus
      should lead to a reduction in the incidence of cognitive impairment due to
      vascular causes. There is evidence that treatment of hypertension can lead to a
      reduction in the incidence of cognitive impairment and dementia, and that
      treatment of VaD with acetylcholinesterase inhibitors may be beneficial.
      CONCLUSIONS: Careful attention needs to be given to controlling vascular risk
      factors in at-risk patients. Pharmacists should play an active role in this
      important area of geriatric pharmacotherapy.

PMID- 19584391
TI  - Decreased INR response secondary to warfarin-flucloxacillin interaction.

PMID- 19584392
TI  - The impact of methodological approach on cost findings in comparison of epoetin
      alfa with darbepoetin alfa.
AB  - BACKGROUND: Two erythropoiesis-stimulating agents (ESAs), epoetin alfa and
      darbepoetin alfa, are approved for the treatment of chemotherapy-induced anemia
      in patients with cancer. Randomized controlled trials indicate that the drugs are
      similarly efficacious, but that the duration of clinical benefit (DCB) ranges
      from 2 to 7 days for epoetin alfa and from 7 to 21 days for darbepoetin alfa,
      depending on dose. Given equivalent efficacy, payers are increasingly interested
      in understanding the cost differences for these 2 drugs. OBJECTIVE: To examine
      the impact of different methodological approaches on the cost comparison between
      epoetin alfa and darbepoetin alfa users, with cancer from a payer perspective.
      METHODS: Episodes of care (episode) were constructed for cancer patients treated
      with ESAs, using MarketScan claims data. Episodes started with the first ESA
      claim and ended on the last ESA claim or the claim before a 42-day or longer gap
      in ESA therapy. Each episode was augmented with an estimated DCB based on the
      last dose in the episode. Cost was reimbursed amount observed in the claims
      database. Adjusted weekly cost was estimated using generalized linear models to
      control for difference in clinical and demographic differences across epoetin
      alfa and darbepoetin alfa episodes. RESULTS: Episodes were created in 324
      darbepoetin alfa and 342 epoetin alfa users. Darbepoetin alfa users tended to be
      younger, had more comorbidities, and had advanced cancer (all p < 0.001). After
      accounting for DCB, the average weekly cost of darbepoetin alfa was significantly
      lower than that of epoetin alfa ($619 vs $940; p < 0.001). After multivariate
      adjustment, darbepoetin alfa had lower costs than epoetin alfa in the base case
      and all alternative approaches. CONCLUSIONS: To reduce the risk of potential
      bias, DCB and different patient characteristics should be taken into account when
      using retrospective claims data to conduct cost comparisons between agents that
      have significant differences in dosing schedule.

PMID- 19584393
TI  - Agreement between pharmacists for problem identification: an initial quality
      measurement of cognitive services.
AB  - BACKGROUND: Recent changes in national reimbursement policies expand the ability
      of pharmacists to seek reimbursement for cognitive services. The quality of
      pharmacist-provided cognitive services has, until now, remained unassessed.
      Pharmacists should demonstrate the quality and value of their work to ensure the
      continued and expanded acceptance of reimbursement for their services. A
      preliminary step in assessing quality is to compare agreement between pharmacists
      for basic problem identification. OBJECTIVE: To quantify agreement between
      pharmacist reviewers for problem identification among Utah Medicaid recipients.
      METHODS: Five pharmacists retrospectively reviewed drug regimens, patient
      characteristics, diagnosis codes, and procedures for 80 Medicaid patients in
      September 2008 and identified drug-related problems (DRPs) in 15 predetermined
      categories. Data for each patient were reviewed twice, and each combination of 2
      pharmacists reviewed the same 8 patients' information. We calculated a
      reliability coefficient to compare the number of DRPs identified and used
      prevalence and bias adjusted kappa (PABAK) to determine interrater reliability
      for the presence of a specific DRP. RESULTS: Of the 15 DRPs categorized by
      pharmacist reviewers, 1 (untreated indications) had a PABAK coefficient of 0.20,
      indicating a relatively low level of agreement between reviewers. All other DRP
      categories had good to excellent agreement, with PABAK coefficients ranging
      between 0.43 and 0.98. CONCLUSIONS: Pharmacist reviewers exhibited less
      variability in DRP identification or categorization than had been expected for
      most categories. This work supports the conclusion that pharmacists in our center
      provide a basic and necessary level of quality for problem assessment. Future
      work is needed to document the impact of this quality on patient outcomes.

PMID- 19584394
TI  - Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate evidence for use of aromatase inhibitors for ovulation
      induction and pregnancy in patients with polycystic ovary syndrome (PCOS). DATA
      SOURCES: A MEDLINE search (1966-May 2009) was conducted using the search terms
      anastrozole, aromatase inhibitors, exemestane, letrozole, ovulation, and
      polycystic ovary syndrome to identify relevant studies. STUDY SELECTION AND DATA
      EXTRACTION: Prospective clinical trials published in English and conducted in
      humans were identified. Trials using intrauterine insemination methods for
      pregnancy were excluded. The resulting articles were separated into 2 groups:
      aromatase inhibitor use in clomiphene-resistant patients and use in treatment
      naive patients. Eleven trials were reviewed. DATA SYNTHESIS: Accepted
      pharmacologic treatments for women with PCOS and infertility include clomiphene
      citrate, gonadotropins, and gonadotropin-releasing hormone (GnRH) analogs. Each
      medication has variable efficacy rates and adverse effects. Therefore, other
      treatments are needed for a subset of women with PCOS and infertility. Evidence
      suggests that nonsteroidal aromatase inhibitors, specifically letrozole and
      anastrozole, may have ovulation-inducing effects by inhibiting androgen-to
      estrogen conversion. Select trials with aromatase inhibitors have demonstrated
      efficacy for increased endometrium thickness, ovulation rates, and pregnancy
      rates when used in clomiphene citrate-resistant or treatment-naive patients.
      CONCLUSIONS: Further trials comparing aromatase inhibitors with clomiphene
      citrate are necessary before aromatase inhibitors can be recommended routinely
      for ovulation induction in women with PCOS and infertility. However, aromatase
      inhibitors may be considered in a subset of this population, specifically women
      who are clomiphene citrate resistant or those who, after discussion of risks and
      benefits, are not candidates for clomiphene citrate, gonadotropins, or GnRH
      analogs.

PMID- 19584395
TI  - Sex differences in inappropriate drug use: a register-based study of over 600,000
      older people.
AB  - BACKGROUND: Several studies have observed a higher rate of inappropriate drug use
      in elderly women than in elderly men, although few have focused explicitly on sex
      differences. Also, educational level (a measure of socioeconomic status) has been
      associated with both polypharmacy and inappropriate drug use in the elderly
      population, which could explain sex differences in inappropriate drug use.
      OBJECTIVE: To investigate whether sex is associated with inappropriate drug use
      in a large general population of older people, after adjustment for age,
      socioeconomic status (ie, educational level), and comorbidity (ie, number of
      drugs). METHODS: We conducted an analysis of data on sex, age, dispensed drugs,
      and education for people aged 75-89 years who were registered in the Swedish
      Prescribed Drug Register between July and October 2005 (N = 645,429). The main
      outcome measures were the filling of prescriptions for anticholinergic drugs or
      long-acting benzodiazepines, concurrent use of 3 or more psychotropic drugs, and
      potentially serious drug-drug interactions. RESULTS: Potentially inappropriate
      drug use was more common in women (24.6%) than in men (19.3%). More women than
      men were exposed to all types of inappropriate drug use, except for potentially
      serious drug-drug interactions. Logistic regression analysis showed that women
      were more likely to be exposed to potentially inappropriate drug use than were
      men (OR 1.24; 95% CI 1.23 to 1.26) after adjustment for age, education, and
      number of drugs (used as a proxy for comorbidity). In particular, female sex was
      highly associated with inappropriate psychotropic use (eg, long-acting
      benzodiazepines: adjusted OR [ORadjusted] 1.45; 95% CI 1.42 to 1.49; >3
      psychotropic drugs: ORadjusted 1.50; 95% CI 1.47 to 1.53). In contrast, women had
      a lower probability of potentially serious drug-drug interactions than did men
      (ORadjusted 0.81; 95% CI 0.80 to 0.83). CONCLUSIONS: Inappropriate drug use in
      the elderly should be monitored separately for women and men. Our results suggest
      that neither socioeconomic status nor comorbidity seem to explain sex differences
      in inappropriate drug use. Future research in other large study populations is
      needed for investigation of other explanations behind these sex differences.

PMID- 19584396
TI  - Coagulation and innate immune responses: can we view them separately?
AB  - The horseshoe crab is often referred to as a "living fossil," representative of
      the oldest classes of arthropods, almost identical to species in existence more
      than 500 million years ago. Comparative analyses of the defense mechanisms used
      by the horseshoe crab that allowed it to survive mostly unchanged throughout the
      millennia reveal a common ancestry of the coagulation and innate immune systems
      that are totally integrated-indeed, almost inseparable. In human biology, we
      traditionally view the hemostatic pathways and those regulating innate immune
      responses to infections and tissue damage as entirely separate entities. But are
      they? The last couple of decades have revealed a remarkable degree of interplay
      between these systems, and the linking cellular and molecular mechanisms are
      rapidly being delineated. In this review, we present some of the major points of
      intersection between coagulation and innate immunity. We attempt to highlight the
      potential impact of these findings by identifying recently established paradigms
      that will hopefully result in the emergence of new strategies to treat a range of
      inflammatory and hemostatic disorders.

PMID- 19584397
TI  - A nonfibrin macromolecular cofactor for tPA-mediated plasmin generation following
      cellular injury.
AB  - Tissue-type plasminogen activator (tPA) is an extracellular protease that
      converts plasminogen into plasmin. For tPA to generate plasmin under biologic
      conditions, a cofactor must first bring tPA and plasminogen into physical
      proximity. Fibrin provides this cofactor for tPA-mediated plasmin generation in
      blood. Despite being naturally devoid of fibrin(ogen), tPA-mediated plasmin
      formation also occurs in the brain. The fibrin-like cofactor(s) that facilitates
      plasmin formation in the injured brain has remained unknown. Here we show that
      protein aggregates formed during neuronal injury provide a macromolecular,
      nonfibrin cofactor that promotes tPA-mediated plasmin formation and subsequent
      cell breakdown. The binding of plasminogen and tPA to these protein aggregates
      occurs via distinct mechanisms. Importantly, nonneuronal cell types also exhibit
      this cofactor effect upon injury, indicating a general phenomenon. This novel
      cofactor identified in nonviable cells has ramifications for ischemic stroke
      where tPA is used clinically and where plasmin activity within the injured brain
      is unwanted. A means of selectively inhibiting the binding of tPA to nonviable
      cells while preserving its association with fibrin may be of benefit for the
      treatment of ischemic stroke.

PMID- 19584398
TI  - miR-34a contributes to megakaryocytic differentiation of K562 cells independently
      of p53.
AB  - The role of miRNAs in regulating megakaryocyte differentiation was examined using
      bipotent K562 human leukemia cells. miR-34a is strongly up-regulated during
      phorbol ester-induced megakaryocyte differentiation, but not during hemin-induced
      erythrocyte differentiation. Enforced expression of miR-34a in K562 cells
      inhibits cell proliferation, induces cell-cycle arrest in G(1) phase, and
      promotes megakaryocyte differentiation as measured by CD41 induction. miR-34a
      expression is also up-regulated during thrombopoietin-induced differentiation of
      CD34(+) hematopoietic precursors, and its enforced expression in these cells
      significantly increases the number of megakaryocyte colonies. miR-34a directly
      regulates expression of MYB, facilitating megakaryocyte differentiation, and of
      CDK4 and CDK6, to inhibit the G(1)/S transition. However, these miR-34a target
      genes are down-regulated rapidly after inducing megakaryocyte differentiation
      before miR-34a is induced. This suggests that miR-34a is not responsible for the
      initial down-regulation but may contribute to maintaining their suppression later
      on. Previous studies have implicated miR-34a as a tumor suppressor gene whose
      transcription is activated by p53. However, in p53-null K562 cells, phorbol
      esters induce miR-34a expression independently of p53 by activating an
      alternative phorbol ester-responsive promoter to produce a longer pri-miR-34a
      transcript.

PMID- 19584399
TI  - Hyperfunctional C3 convertase leads to complement deposition on endothelial cells
      and contributes to atypical hemolytic uremic syndrome.
AB  - Complement is a major innate immune defense against pathogens, tightly regulated
      to prevent host tissue damage. Atypical hemolytic uremic syndrome (aHUS) is
      characterized by endothelial damage leading to renal failure and is highly
      associated with abnormal alternative pathway regulation. We characterized the
      functional consequences of 2 aHUS-associated mutations (D(254)G and K(325)N) in
      factor B, a key participant in the alternative C3 convertase. Mutant proteins
      formed high-affinity C3-binding site, leading to a hyperfunctional C3 convertase,
      resistant to decay by factor H. This led to enhanced complement deposition on the
      surface of alternative pathway activator cells. In contrast to native factor B,
      the 2 mutants bound to inactivated C3 and induced formation of functional C3
      convertase on iC3b-coated surface. We demonstrated for the first time that factor
      B mutations lead to enhanced C3-fragment deposition on quiescent and adherent
      human glomerular cells (GEnCs) and human umbilical vein endothelial cells
      (HUVECs), together with the formation of sC5b-9 complexes. These results could
      explain the occurrence of the disease, since excessive complement deposition on
      endothelial cells is a central event in the pathogenesis of aHUS. Therefore, risk
      factors for aHUS are not only mutations leading to loss of regulation, but also
      mutations, resulting in hyperactive C3 convertase.

PMID- 19584401
TI  - Enrichment of Sca1+ hematopoietic progenitors in polycythemic mice inhibits
      leukemogenesis.
AB  - Polycythemia vera (PV) is a myeloproliferative disorder characterized by a
      pronounced increase in the number of erythroid cells. However, despite this
      aberrant proliferation, the incidence of erythroleukemia is paradoxically rare in
      PV patients. In this study, we show that the progression of Friend virus-induced
      erythroleukemia is delayed in a mouse model of primary familial congenital
      polycythemia in which the wild-type Epo-receptor (EpoR) gene is replaced with a
      truncated human EPOR gene. Herein, we show that these mice exhibit enrichment of
      Sca1(+)/cKit(-) progenitors and several mature immune cells, such as dendritic
      cells and macrophages. In cotransplantation experiments, Sca1(+)/cKit(-)
      progenitors inhibit the tumorigenicity of Sca1(-)/cKit(+) erythroleukemic cells.
      A cell line established from Sca1(+)/cKit(-) progenitors is also capable of
      inhibiting leukemic proliferation in culture and in mice. This phenomenon of
      leukemic inhibition, also detected in the serum of PV patients, is partially
      attributed to increased nitric oxide secretion. In addition, the administration
      of erythropoietin into leukemic mice induces a polycythemia-like state associated
      with the expansion of Sca1(+)/cKit(-) progenitors and derivative immune cells,
      thereby inhibiting leukemia progression. This study indicates that a combination
      therapy incorporating the enrichment of Sca1(+)/cKit(-) progenitors may serve as
      a novel approach for the treatment of leukemia.

PMID- 19584400
TI  - A risk-adapted, response-based approach using ABVE-PC for children and
      adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of
      P9425.
AB  - Current treatment strategies for Hodgkin lymphoma result in excellent survival
      but often confer significant long-term toxicity. We designed ABVE-PC
      (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to
      (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of
      long-term sequelae by response-based reduction of cumulative chemotherapy.
      Efficient induction of early response by dose-dense drug delivery supported an
      early-response-adapted therapeutic paradigm. The 216 eligible patients were
      younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC
      was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles
      received 21 Gy radiation to involved regions; RER was documented in 63% of
      patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy
      radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the
      slow early responders (P = .85). Only 1% of patients had progressive disease.
      Five-year overall survival was 95%. With this regimen, cumulative doses of
      alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually
      associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen
      that provides outstanding event-free survival/overall survival with short
      duration, early-response-adapted therapy.

PMID- 19584402
TI  - Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of
      adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL) is a malignant lymphoproliferative disorder
      caused by HTLV-I infection. In ATL, chemotherapeutic responses are generally
      poor, which has suggested the existence of chemotherapy-resistant cancer stem
      cells (CSCs). To identify CSC candidates in ATL, we have focused on a Tax
      transgenic mouse (Tax-Tg) model, which reproduces ATL-like disease both in Tax-Tg
      animals and also after transfer of Tax-Tg splenic lymphomatous cells (SLCs) to
      nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Using a
      limiting dilution transplantation, it was estimated that one CSC existed per
      10(4) SLCs (0.01%). In agreement with this, we have successfully identified
      candidate CSCs in a side population (0.06%), which overlapped with a minor
      population of CD38(-)/CD71(-)/CD117(+) cells (0.03%). Whereas lymphoma did not
      develop after transplantation of 10(2) SLCs, 10(2) CSCs could consistently
      regenerate the original lymphoma. In addition, lymphoma and CSCs could also be
      demonstrated in the bone marrow and CD117(+) CSCs were observed in both
      osteoblastic and vascular niches. In the CSCs, Tax, Notch1, and Bmi1 expression
      was down-regulated, suggesting that the CSCs were derived from Pro-T cells or
      early hematopoietic progenitor cells. Taken together, our data demonstrate that
      CSCs certainly exist and have the potential to regenerate lymphoma in our mouse
      model.

PMID- 19584403
TI  - Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C.
AB  - Acute myelogenous leukemia is driven by leukemic stem cells (LSCs) generated by
      mutations that confer (or maintain) self-renewal potential coupled to an aberrant
      differentiation program. Using retroviral mutagenesis, we identified genes that
      generate LSCs in collaboration with genetic disruption of the gene encoding
      interferon response factor 8 (Irf8), which induces a myeloproliferation in vivo.
      Among the targeted genes, we identified Mef2c, encoding a MCM1-agamous-deficiens
      serum response factor transcription factor, and confirmed that overexpression
      induced a myelomonocytic leukemia in cooperation with Irf8 deficiency.
      Strikingly, several of the genes identified in our screen have been reported to
      be up-regulated in the mixed-lineage leukemia (MLL) subtype. High MEF2C
      expression levels were confirmed in acute myelogenous leukemia patient samples
      with MLL gene disruptions, prompting an investigation of the causal interplay.
      Using a conditional mouse strain, we demonstrated that Mef2c deficiency does not
      impair the establishment or maintenance of LSCs generated in vitro by MLL/ENL
      fusion proteins; however, its loss led to compromised homing and invasiveness of
      the tumor cells. Mef2c-dependent targets included several genes encoding matrix
      metalloproteinases and chemokine ligands and receptors, providing a mechanistic
      link to increased homing and motility. Thus, MEF2C up-regulation may be
      responsible for the aggressive nature of this leukemia subtype.

PMID- 19584405
TI  - The prevalence of middle eastern extremist ideologies among some canadian
      offenders.
AB  - The Belief Diversity Scale (BDS) was administered to 89 male Canadian offenders
      of different religious backgrounds. The BDS is a 33-item, sixsubscale instrument
      designed to quantitatively measure the religious attitudes, beliefs, and
      ideologies of Middle Eastern extremists on risk areas described in the
      literature. Results indicated that the Muslim offenders scored much higher than
      and significantly different from both the Christian and atheist groups on the
      BDS. Results also suggested the prevalence of Middle Eastern extremist ideologies
      among the Muslim offenders involved in this study.

PMID- 19584404
TI  - Identification of endogenous acyl amino acids based on a targeted lipidomics
      approach.
AB  - Using a partially purified bovine brain extract, our lab identified three novel
      endogenous acyl amino acids in mammalian tissues. The presence of numerous amino
      acids in the body and their ability to form amides with several saturated and
      unsaturated fatty acids indicated the potential existence of a large number of
      heretofore unidentified acyl amino acids. Reports of several additional acyl
      amino acids that activate G-protein coupled receptors (e.g., N-arachidonoyl
      glycine, N-arachidonoyl serine) and transient receptor potential channels (e.g.,
      N-arachidonoyl dopamine, N-acyl taurines) suggested that some or many novel acyl
      amino acids could serve as signaling molecules. Here, we used a targeted
      lipidomics approach including specific enrichment steps, nano-LC/MS/MS, high
      throughput screening of the datasets with a potent search algorithm based on
      fragment ion analysis, and quantification using the multiple reaction monitoring
      mode in Analyst software to measure the biological levels of acyl amino acids in
      rat brain. We successfully identified 50 novel endogenous acyl amino acids
      present at 0.2 to 69 pmol g(-1) wet rat brain.

PMID- 19584406
TI  - Psychosocial correlates of physical dating violence victimization among Latino
      early adolescents.
AB  - This study examined the association between dating violence victimization and
      psychosocial risk and protective factors among Latino early adolescents. An
      anonymous, cross-sectional, self-reported survey was administered to a
      convenience sample of Latino youth (n = 322) aged 11 to 13 residing in suburban
      Washington, D.C. The dependent variable was physical dating violence; the
      independent variables included violence, substance use, emotional well-being,
      prosocial behaviors, and parenting practices. Multivariate logistic regression
      models were constructed and adjusted odds ratio and 95% confidence interval were
      examined. Overall, 13.5% (n = 43) of Latino early adolescents reported being a
      victim of physical dating violence within the past year. The prevalence was 14.4%
      for girls and 12.9% for boys. Among the girls, binge drinking was the sole risk
      behavior associated with dating violence. Gun carrying, alcohol consumption, and
      having considered suicide were associated with dating violence among the boys.
      Physical dating violence appears to affect a small but significant proportion of
      Latino early adolescents and is associated with other risk behaviors. Healthy
      dating relationship programs are warranted for middle school youth with some
      tailoring to reflect gender differences in risk profiles.

PMID- 19584407
TI  - The impact of protective factors in desistance from violent reoffending: a study
      in three samples of adolescent offenders.
AB  - This study examined the impact of protective factors, assessed by means of the
      Structured Assessment of Violence Risk in Youth (SAVRY), on desistance from
      violent reoffending in adolescents. Three samples included male adolescents in
      different stages of the judicial process: pre-trial (n = 111); during residential
      treatment (n = 66); and after release from a juvenile justice facility ( n = 47).
      The results lend support to the hypothesis that protective factors buffer or
      mitigate the risk of violent reoffending. Using regression analyses, in all
      samples, the addition of protective factors yielded a significant increment in
      the amount of variance explained by dynamic risk factors alone. Furthermore, in
      medium to high risk subgroups, the violent reoffending rate was significantly
      higher when protective factors were absent, compared to when protective factors
      were present. These findings are discussed in terms of their implications for
      risk assessment and risk management practice with adolescent offenders.

PMID- 19584408
TI  - Health outcomes of youth development programme in England: prospective matched
      comparison study.
AB  - OBJECTIVE: To evaluate the effectiveness of youth development in reducing teenage
      pregnancy, substance use, and other outcomes. DESIGN: Prospective matched
      comparison study. SETTING: 54 youth service sites in England. PARTICIPANTS: Young
      people (n=2724) aged 13-15 years at baseline deemed by professionals as at risk
      of teenage pregnancy, substance misuse, or school exclusion or to be vulnerable.
      INTERVENTION: Intensive, multicomponent youth development programme including sex
      and drugs education (Young People's Development Programme) versus standard youth
      provision. MAIN OUTCOME MEASURES: Various, including pregnancy, weekly cannabis
      use, and monthly drunkenness at 18 months. RESULTS: Young women in the
      intervention group more commonly reported pregnancy than did those in the
      comparison group (16% v 6%; adjusted odds ratio 3.55, 95% confidence interval
      1.32 to 9.50). Young women in the intervention group also more commonly reported
      early heterosexual experience (58% v 33%; adjusted odds ratio 2.53, 1.09 to 5.92)
      and expectation of teenage parenthood (34% v 24%; 1.61, 1.07 to 2.43).
      CONCLUSIONS: No evidence was found that the intervention was effective in
      delaying heterosexual experience or reducing pregnancies, drunkenness, or
      cannabis use. Some results suggested an adverse effect. Although methodological
      limitations may at least partly explain these findings, any further
      implementation of such interventions in the UK should be only within randomised
      trials.

PMID- 19584409
TI  - An independent external validation and evaluation of QRISK cardiovascular risk
      prediction: a prospective open cohort study.
AB  - OBJECTIVE: To independently evaluate the performance of the QRISK score for
      predicting 10 year risk of cardiovascular disease in an independent UK cohort of
      patients from general practice and compare the performance with Framingham
      equations. DESIGN: Prospective open cohort study. SETTING: 274 practices from
      England and Wales contributing to the THIN database. PARTICIPANTS: 1.07 million
      patients, registered between 1 January 1995 and 1 April 2006, aged 35-74 years
      (5.4 million person years) with 43 990 cardiovascular events. MAIN OUTCOME
      MEASURES: First diagnosis of cardiovascular disease (myocardial infarction,
      coronary heart disease, stroke, and transient ischaemic attack) recorded in
      general practice records. RESULTS: This independent validation indicated that
      QRISK offers an improved performance in predicting the 10 year risk of
      cardiovascular disease in a large cohort of UK patients over the Anderson
      Framingham equation. Discrimination and calibration statistics were better with
      QRISK. QRISK explained 32% of the variation in men and 37% in women, compared
      with 27% and 31% respectively for Anderson Framingham. QRISK underpredicted risk
      by 13% for men and 10% for women, whereas Anderson Framingham overpredicted risk
      by 32% for men and 10% for women. In total, 85 010 (8%) of patients would be
      reclassified from high risk (>or=20%) with Anderson Framingham to low risk with
      QRISK, with an observed 10 year cardiovascular disease risk of 17.5% (95%
      confidence interval 16.9% to 18.1%) for men and 16.8% (15.7% to 18.0%) for women.
      The incidence rate of cardiovascular disease events among men was 30.5 per 1000
      person years (95% confidence interval 29.9 to 31.2) in high risk patients
      identified with QRISK and 23.7 per 1000 person years (23.2 to 24.1) in high risk
      patients identified with Anderson Framingham. Similarly, the incidence rate of
      cardiovascular disease events among women was 26.7 per 1000 person years (25.8 to
      27.7) in high risk patients identified with QRISK compared with 22.2 per 1000
      person years (21.4 to 23.0) in high risk patients identified with Anderson
      Framingham. CONCLUSIONS: The QRISK cardiovascular disease risk equation offers an
      improvement over the long established Anderson Framingham equation in terms of
      identifying a high risk population for cardiovascular disease in the United
      Kingdom. QRISK underestimates 10 year cardiovascular disease risk, but the
      magnitude of underprediction is smaller than the overprediction with Anderson
      Framingham.

PMID- 19584410
TI  - QRISK or Framingham for predicting cardiovascular risk?

PMID- 19584412
TI  - The vote of acute medical inpatients: a prospective study.
AB  - OBJECTIVE: There may be ethical issues associated with allowing certain
      inpatients to vote as some may be cognitively impaired. During the 2007 elections
      in France, we conducted a prospective observational study on voting among
      hospitalized patients. METHOD: Patients hospitalized in an Internal Medicine and
      Geriatric Department on election day were included. The primary outcome was the
      turnout among registered inpatients, and secondary outcomes were Mini-Mental
      State Examination (MMSE) scores and reasons for abstention. RESULTS: Of 142
      inpatients (mean age 73 years), 84 were eligible to vote, and 22 actually voted
      (turnout 25.2%). Among the voters, 23% had an MMSE score of less than 12; 58% of
      abstentions were procedure-related. DISCUSSION: In our study, some inpatients did
      not vote as a result of procedural issues. When patients with severe cognitive
      impairment vote, there is a potential risk of vote diversion. Voting procedures
      should be improved to give inpatients easier access to the ballot while
      protecting them from the risk of fraud.

PMID- 19584411
TI  - Black-White disparities in disability among older Americans: further untangling
      the role of race and socioeconomic status.
AB  - OBJECTIVE: To explore the impact of adjusting for income and education on
      disparities in functional limitations and limitations in activities of daily
      living (ADLs) between Black and White older Americans. METHOD: Data from the 2003
      American Community Survey were used to examine the associations of education and
      income, stratified by race and gender, with functional limitations and ADLs, in a
      sample of 16,870 non-Hispanic Blacks and 186,086 non-Hispanic Whites aged 55 to
      74. Sequential logistic regressions were used to examine the relative
      contribution of income and education to racial disparities. RESULTS: Ninety
      percent of the Black-White difference in disability rates for men and 75% of the
      difference for women aged 55 to 64 were explained by income and education.
      DISCUSSION: The greatly elevated risk of disability among Blacks aged 55 to 74 is
      largely explained by differences in socioeconomic status. Reductions in Black
      White health disparities require a better understanding of the mechanisms whereby
      lower income and education are associated with functional outcomes in older
      persons.

PMID- 19584413
TI  - Differentials by socioeconomic status and institutional characteristics in
      preventive service utilization by older persons in Costa Rica.
AB  - Objective.The goals of this article are to assess the level of preventive service
      utilization by older persons in Costa Rica and to determine whether there are
      differentials in utilization across socioeconomic status (SES) and institutional
      characteristics. Method. Using data from the Costa Rican Study on Longevity and
      Healthy Aging (CRELES) project, a study of healthy aging in Costa Rica, the
      authors use self-reported information on preventive service utilization. The SES
      differentials are studied using logistic regressions. Results. Preventive
      services linked to cardiovascular disease prevention are frequently utilized;
      preventive services linked to cancer screening, vaccination, and sense
      impairments are not so widely used. Higher SES people are more likely to utilize
      most preventive services. Utilization rates among uninsured seniors are lower
      than among their insured peers. Home visits by community health workers are
      positively associated with higher utilization rates. Discussion. The SES
      disparities in preventive service utilization exist in Costa Rica, and
      institutional characteristics are positively associated with increasing
      utilization.

PMID- 19584414
TI  - Dielectric function of ZnTe nanocrystals by spectroscopic ellipsometry.
AB  - We have studied the optical properties of ZnTe nanocrystals (ZnTe-nc) by
      spectroscopic ellipsometry. The ZnTe-nc are embedded in a SiO2 matrix by an ion
      implantation technique. Two doses of 1 x 10(16) and 5 x 10(15) cm(-2) of
      tellurium and zinc ions are implanted in a 250 nm thick SiO2 layer thermally
      grown on silicon with respective implantation energies of 180 and 115 keV.
      Subsequent thermal treatments at 800 degrees C lead to the formation of ZnTe-nc.
      Their sizes are characterized by transmission electron microscopy. The ZnTe-nc
      obtained with the 1 x 10(16) cm(-2) dose are self-organized into two layers
      parallel to the surface. Their mean radius ranges between 4-17 nm and 7-17 nm.
      The ZnTe-nc obtained with the 5 x 10(15) cm(-2) dose are self-organized into one
      layer with a mean radius between 4-17 nm. A critical points (CPs) dispersion
      model is used to extract the optical responses of the ZnTe-nc. The optical
      properties such as the dielectric function and the second derivative of the
      dielectric function are presented and analyzed. The dielectric function spectra
      reveal distinct structures attributed to band gap and optical transitions at
      higher energy. The correlation between the optical responses and the size of the
      nanocrystals is also given.

PMID- 19584415
TI  - The formation of carbon nanostructures by in situ TEM mechanical nanoscale
      fatigue and fracture of carbon thin films.
AB  - A technique to quantify in real time the microstructural changes occurring during
      mechanical nanoscale fatigue of ultrathin surface coatings has been developed.
      Cyclic nanoscale loading, with amplitudes less than 100 nm, is achieved with a
      mechanical probe miniaturized to fit inside a transmission electron microscope
      (TEM). The TEM tribological probe can be used for nanofriction and nanofatigue
      testing, with 3D control of the loading direction and simultaneous TEM imaging of
      the nano-objects. It is demonstrated that fracture of 10-20 nm thick amorphous
      carbon films on sharp gold asperities, by a single nanoscale shear impact,
      results in the formation of <10 nm diameter amorphous carbon filaments. Failure
      of the same carbon films after cyclic nanofatigue, however, results in the
      formation of carbon nanostructures with a significant degree of graphitic
      ordering, including a carbon onion.

PMID- 19584416
TI  - The shape evolution of gold seeds and gold@silver core-shell nanostructures.
AB  - We report the seed-dependent shape evolution of gold@silver (Au@Ag) core-shell
      nanostructures with various morphologies through using pre-existing Au
      nanocrystals as nuclei in a polyvinylpyrrolidone (PVP)-assisted polyol reduction
      process. Au nanocrystalline seeds with different shapes such as cube, truncated
      octahedron, octahedron, twinned hexagon and triangle, five-twinned decahedron and
      nanorod are firstly synthesized by refluxing a 1,5-pentanediol solution
      containing Au precursors in the presence of PVP. The Au seeds obtained in this
      way then serve as the nuclei for further epitaxial growth of Ag shells by using
      Ag precursors via the same route. Scanning transmission electron microscope
      (STEM) characterization of the products obtained demonstrates that the
      morphological evolution of the Ag shells depends completely on the shapes of the
      Au seeds that are used. We have observed that the Au@Ag core-shell nanostructures
      formed with various regular shapes such as cube, bi-triangle, and nanorod with
      five-twinned cross section, are mostly surrounded by {100}-type Ag crystalline
      facets. Our findings provide new evidence and clear evolution routines from the
      Au cores with well-defined shapes to the corresponding Ag shells for the Au@Ag
      core-shell nanostructures by the family of the PVP-assisted polyol reduction
      methods.

PMID- 19584417
TI  - The hydrophobicity of a lotus leaf: a nanomechanical and computational approach.
AB  - The multi-scale microstructure of a lotus leaf is rendered non-wetting by micro
      protrusions and nano-hairs present on its surface. The mechanical properties of
      the surface become important since the water droplet has to be supported on the
      micro-protrusions without wetting the surface. Current work correlates the non
      wetting behavior of the lotus leaf with its mechanical properties (Young's
      modulus and critical flexing stress) and areal spread of micro-protrusions on the
      leaf surface. Quasistatic nanoindentation of nano-hairs on the lotus leaf surface
      has shown a variation of elastic modulus between 359 and 870 MPa, which in turn
      dictates the critical flexing strength and consequent non-wetting. Computational
      fluid dynamics modeling is utilized to correlate wetting phenomena with the areal
      spread of micro-protrusions. A qualitative model is proposed for the way nature
      has chosen to render the lotus leaf surface non-wetting.

PMID- 19584418
TI  - Temperature-dependent low electric field charging of Si nanocrystals embedded
      within oxide-nitride-oxide dielectric stacks.
AB  - In this work we examine the current peaks and the negative differential
      resistance that appear in the low electric field regime of oxide-nitride-oxide
      structures with a two-dimensional band of silicon nanocrystals embedded in a
      nitride layer. The silicon nanocrystals were synthesized by low energy ion
      implantation (1 keV, 1.5 x 10(16) Si(+) cm(-2)) and subsequent thermal annealing
      (950 degrees C, 30 min). Electrical examination was performed at temperatures
      from 20 to 100 degrees C using constant voltage ramp-rate current measurements.
      This approach enables us to determine the origin of the observed current peaks as
      well as to extract the trapping location of the injected carriers within the
      dielectric stack. The results confirm that the carriers are trapped within the Si
      nanocrystal band, verifying that this region corresponds to energy minima of the
      dielectric stack.

PMID- 19584419
TI  - Homogeneous core/shell ZnO/ZnMgO quantum well heterostructures on vertical ZnO
      nanowires.
AB  - Low-area density ZnO nanowire arrays, growing perpendicularly to the substrate,
      are synthesized with high-pressure pulsed laser deposition. The introduction of a
      ZnO buffer layer enables us to fabricate individual nanowires several micrometres
      apart (area density<0.1 nanowire microm(-2)), suppressing any shadowing effect by
      neighbouring nanowires during subsequent growth. These low density ZnO nanowires,
      whose c-axis is perpendicular to the substrate surface, are then used as
      templates to grow ZnO/ZnMgO core-shell nanowire heterostructures with
      conventional low-pressure pulsed laser deposition. Cathodoluminescence
      spectroscopy as well as transmission electron microscopy show that a sharp
      interface forms between the ZnO core and the ZnMgO shell. Based on these
      findings, we have grown a series of radial ZnO/ZnMgO quantum wells with different
      thicknesses that exhibit quantum confinement effects, with thicker quantum wells
      emitting at lower energies. Spatially resolved cathodoluminescence confirms the
      homogeneity of the quantum well structure along the full nanowire length of about
      3 microm.

PMID- 19584420
TI  - Species enrichment of SWNTs with pyrene alkylamide derivatives: is the alkyl
      chain length important?
AB  - Three similar amide-functionalized pyrene derivatives (N-methyl(18-Crown-6)pyrene
      1-acetamide, N-methyl(18-Crown-6)pyrene-1-butyramide and N-methyl (18-Crown
      6)pyrene-1-formamide), denoted as pa-18-C-6, pb-18-C-6 and pc-18-C-6,
      respectively, with different alkyl chain lengths between the amide groups and
      pyrene moieties have been successfully synthesized and for the first time, their
      separation effects on single-walled carbon nanotubes (SWNTs) according to their
      electronic structures (metallic/semiconducting) and diameter have been
      demonstrated. Resonant Raman spectroscopy and UV-vis-NIR show that all three
      pyrene derivatives are selective to metallic SWNTs (met-SWNTs). Resonant Raman
      scattering (RRS) spectra also indicate that two of the pyrene derivatives, pb-18
      C-6 and pc-18-C-6, are selective to large-diameter (D>1 nm) met-SWNTs. The third
      compound, pa-18-C-6, is selective to small-diameter (D<1.03 nm) met-SWNTs due to
      the ketone-to-enol rearrangement resulting in higher strain force relaxation; the
      rearrangement was shown by Fourier-transform infrared spectroscopy data. For
      their discrimination between different relatively large-diameter semiconducting
      species, RRS spectra using a 785 nm laser show that pb-18-C-6 is selective to
      larger diameter ones while pa-18-C-6 and pc-18-C-6 have no selectivity. The
      selectivity for met-SWNTs in the solution is confirmed by a tenfold decline in
      thin film SWNT network resistivity (from 43 to 4.3 S m(-1)) after depletion of
      metallic nanotubes by a four-pass selection procedure using pa-18-C-6 and pc-18-C
      6 surfactants alternately. Further, after the four-pass selection procedure, the
      conductivity of a network using the supernatant SWNTs changes less when heated in
      air compared to another network using the precipitated SWNTs; the high
      conductivity stability of the network with supernatant SWNTs further confirms the
      high content of met-SWNTs which are resistant to carrier doping.

PMID- 19584421
TI  - Frequency dependent enhancement of heat transport in a nanofluid with ZnO
      nanoparticles.
AB  - In this paper we report an observation of an unusual frequency dependent
      enhancement of the heat transport parameter (C(p)kappa, C(p) = heat capacity and
      kappa = thermal conductivity) of a nanofluid containing ZnO nanoparticles of an
      average size of 10 nm (volume fraction<or=1.5%) in ethanol. The enhancement of
      C(p)kappa at low frequency is substantial. C(p)kappa becomes frequency
      independent at low frequency but it shows a strong dependence on the measuring
      frequency where it decreases as the frequency is increased. The enhancement also
      depends on the temperature and also scales with the concentration of ZnO. This
      frequency dependent thermal conductivity of nanofluids cannot be explained by the
      classical effective medium theory. A new model has to be developed to explain the
      above phenomenon. We have suggested local aggregation as the likely cause that
      may give rise to the observed frequency dependence.

PMID- 19584422
TI  - Evolution of metastable phases in silicon during nanoindentation: mechanism
      analysis and experimental verification.
AB  - This paper explores the evolution mechanisms of metastable phases during the
      nanoindentation on monocrystalline silicon. Both the molecular dynamics (MD) and
      the in situ scanning spreading resistance microscopy (SSRM) analyses were carried
      out on Si(100) orientation, and for the first time, experimental verification was
      achieved quantitatively at the same nanoscopic scale. It was found that under
      equivalent indentation loads, the MD prediction agrees extremely well with the
      result experimentally measured using SSRM, in terms of the depth of the residual
      indentation marks and the onset, evolution and dimension variation of the
      metastable phases, such as beta-Sn. A new six-coordinated silicon phase, Si-XIII,
      transformed directly from Si-I was discovered. The investigation showed that
      there is a critical size of contact between the indenter and silicon, beyond
      which a crystal particle of distorted diamond structure will emerge in between
      the indenter and the amorphous phase upon unloading.

PMID- 19584423
TI  - Surface modification on silicon with chitosan and biological research.
AB  - The aim of the present study was to investigate the effect of chitosan
      modification of silicon (Si) on protein adsorption, cell adhesion and cell
      proliferation. Chitosan was first immobilized on the Si surface through a (3
      aminopropyl)triethoxysilane (APTES) bridge. The surface was then characterized by
      contact angle measurement, atomic force microscopy (AFM), x-ray photoelectron
      spectroscopy (XPS) and energy dispersive x-ray spectroscopy (EDX). The amount of
      protein adsorbed on the native Si and chitosan-modified Si surface was evaluated
      by a modified Coomassie brilliant blue (CBB) protein assay. The adhesion and
      proliferation behavior of L-929 and pc12 cells were then assessed by microscopy
      and methylthiazoltetrazolium (MTT) tests. The results showed that the chitosan
      modification could resist protein adsorption and inhibit the adhesion and
      proliferation of two kinds of cells on Si.

PMID- 19584424
TI  - Modification of the bulk properties of the porous poly(lactide-co-glycolide)
      scaffold by irradiation with a cyclotron ion beam with high energy for its
      application in tissue engineering.
AB  - Understanding the bulk properties of a prefabricated scaffold for handling and
      degradation during cell culture may be advantageous to its application in tissue
      engineering. Modification of the bulk properties of the porous poly(lactide-co
      glycolide) (PLGA) scaffold was performed by irradiation with a high energy
      cyclotron proton ion beam. The porous PLGA scaffolds were fabricated in advance
      by the gas-foaming method by employing ammonium bicarbonate particles as
      porogens. Irradiation with ion beams was performed with 40 MeV for 3, 6 and 9 min
      on the scaffolds at a distance of 30 cm from the beam exit to the scaffold
      surface. The bulk area of the ion beam-treated PLGA scaffold apparently
      demonstrated no color changes when observed with a digital camera. The chemical
      structures of the untreated samples seemed to be kept well when analyzed by both
      Fourier transformed infrared but a subtle change was observed in its x-ray
      photoelectron spectroscopy. The results of in vitro tissue culture with smooth
      muscle cells for up to 4 weeks also demonstrated no significant difference in
      terms of its handling stability during cell culture and cellular behavior between
      the untreated PLGA scaffolds and the ion beam-treated ones. However, significant
      changes were observed in its molecular weight as measured by gel permeation
      chromatography, indicating a significant reduction of its molecular weights.
      These results of in vitro tests and GPC measurements indicated that while bulk
      modification of the scaffold was processed, its handling was stable during in
      vitro cell culture for up to 4 weeks.

PMID- 19584425
TI  - Development of epigallocatechin gallate-eluting polymeric stent and its
      physicochemical, biomechanical and biological evaluations.
AB  - Localized drug delivery from drug-eluting stents has been accepted as one of the
      most promising treatment methods for preventing restenosis after stenting.
      However, hypersensitivity reactions caused by their nonresorbable polymer
      coatings and bare-metal stents may result in serious clinical sequelae.
      Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, has been
      shown to exert anti-thrombotic, anti-inflammatory and anti-proliferative
      activities. In this study, it was hypothesized that sustainedly released EGCG
      from biodegradable poly(lactide-co-epsilon-caprolactone, PLCL) would suppress the
      proliferation of vascular smooth muscle cells (VSMCs). EGCG-releasing PLCL (E
      PLCL) was prepared by blending PLCL with EGCG. The surface morphology, roughness
      and melting temperature of PLCL were not changed despite EGCG addition. EGCG was
      uniformly dispersed into E-PLCL and sustainedly released for periods up to 7 days
      by controlled diffusion rather than PLCL degradation. Moreover, EGCG did not
      affect tensile strength at break, but significantly increased the elastic modulus
      of PLCL. The proliferation of VSMCs onto E-PLCL was significantly suppressed
      although the cell attachment onto E-PLCL had been higher than that onto PLCL. On
      the other hand, EGCG-eluting polymeric stents were prepared with neither cracks
      nor webbings between struts, and their structural integrity was maintained
      without delamination or destruction. These results suggest that E-PLCL can be
      potentially applied for fabricating an EGCG-eluting vascular stent, namely an
      EGCG-eluting polymeric stent, or even an EGCG-releasing polymer-coated metal
      stent, to prevent thrombosis, inflammation and in-stent restenosis.

PMID- 19584426
TI  - Biodegradable poly(ester amine)s for gene delivery applications.
AB  - Cationic polymers have been increasingly proposed as potential gene delivery
      vectors because of their versatility. In this paper, we focus on the
      characteristics of poly(ester amine)s (PEAs) as gene delivery carriers,
      degradation pattern as an essential parameter for reduced toxicity,
      classification based on its physicochemical properties followed by its success as
      efficient gene delivery carrier in vitro and in vivo. We also discuss the
      conjugation of ligands/charged groups to the side chain of the polyester in order
      to achieve receptor-mediated endocytosis as well as target-specific delivery of
      DNA. Capable of delivering exogenous genes to a cell nucleus, these cationic PEAs
      also serve as a valuable model to understand the important characteristics that
      render a polymer an effective gene carrier.

PMID- 19584427
TI  - Electrospinning of synthesized triblock copolymers of epsilon-caprolactone and L
      lactide for the application of vascular tissue engineering.
AB  - Biodegradable triblock copolymers of epsilon-caprolactone and L-lactide with
      varying compositions and molecular weights have been synthesized. They were then
      used to fabricate compliant small-diameter tissue engineered vascular scaffolds
      by using an electrospinning technique. The in vitro and in vivo degradation of
      the ultrafine fabrics was monitored to be faster than their counterpart cast
      films. A favorable interaction between the scaffolds and the mouse fibroblast
      L929 cells was demonstrated via MTT assay. A confluent, adherent monolayer of
      canine mesenchymal stem cells was observed in the tubular scaffold lumen after
      culture in a bioreactor for 3 days. The scaffold mechanical strength was strong
      enough to be transplanted into the canine carotid artery.

PMID- 19584428
TI  - Deficits in aversive but not in safe taste memory in the APPswe/PS1dE9 mice.
AB  - Age-related changes in taste memory were evaluated in APPswe/PS1dE9 transgenic
      (Tg) mice and age-matched wild type littermate controls (Wt). These Tg mice
      produce increasing amounts of amyloid-beta in the brain with age, develop
      significant amounts of plaques by 9 months of age, and provide an opportunity to
      study the effects of Alzheimer's disease-like amyloidosis on different aspects of
      taste memory. In groups of mice ranging from 15-16 months of age, the neophobic
      response and its attenuation were similar in Tg and Wt mice. However, conditioned
      taste aversion (CTA), which resulted from the association between a new taste and
      an artificially induced gastric malaise, was significantly reduced in the 15-16
      month old Tg mice compared to the Wt mice, but not in the 3-4 or 7-8 month old
      mice. The extinction of CTA was normal in 3-4 month old Tg mice, but occurred
      more rapidly in the 7-8 and 15-16 months old Tg mice than in the age-matched
      controls. These results provide evidence of differences in the neuronal systems
      involved in the attenuation of neophobia and CTA and suggest that the progressive
      amyloidosis that takes place in APPswe/PS1dE9 mice selectively affects the
      aversion component of taste memory.

PMID- 19584429
TI  - Functional roles of amyloid-beta protein precursor and amyloid-beta peptides:
      evidence from experimental studies.
AB  - Amyloid-beta (Abeta) has remained a central feature in research into Alzheimer's
      disease (AD). Yet the function of the amyloid-beta protein precursor (AbetaPP)
      and its processing products in the central nervous system is controversial. This
      review examines experimental literature from cell cultures to transgenic AD and
      brain injury models with a special emphasis on the functional role of AbetaPP and
      AbetaPP-derived peptides. AbetaPP knock-out mice exhibit severe metabolic
      abnormalities and behavioral deficits, indicating an important physiological
      function of AbetaPP. Also, an increasing body of evidence suggests that while
      Abeta is undoubtedly linked to neurodegeneration, the soluble amino-terminal
      fragment of AbetaPP (sAbetaPPalpha) has neuroprotective, neurotrophic, and cell
      adhesive functions. Moderate overexpression of human AbetaPP in rodents does not
      produce apparent Abeta pathology and has no significant effect on cognitive or
      sensorimotor behavior and, surprisingly, may even provide histological
      neuroprotection against focal cerebral ischemia. In contrast, phenotypes with
      more severe Abeta pathology show impaired cognitive performance, increased
      vulnerability to brain ischemia and trauma, and less favorable functional outcome
      even before Abeta deposition. A delicate balance in AbetaPP processing seems to
      determine its functional consequences. Thus, it is tempting to speculate that
      promotion of alpha-secretase-mediated cleavage of AbetaPP, which leads to
      increased sAbetaPPalpha production, provides a novel therapeutic strategy in the
      treatment of AD and brain injury.

PMID- 19584432
TI  - Complex splicing and neural expression of duplicated tau genes in zebrafish
      embryos.
AB  - Microtubule-associated protein tau (MAPT) is the major component of the
      neurofibrillary tangles found in the brains of those suffering from Alzheimer's
      disease. Various forms of tau lesions are found in other neurodegenerative
      diseases (tauopathies). We report identification of two MAPT paralogous genes in
      zebrafish, mapta and maptb, and analysis of their expression patterns during
      embryonic development. The two paralogues appear to have arisen by duplication of
      an ancestral teleost MAPT orthologue. Analysis of the splicing of transcripts
      from both genes during embryogenesis showed that mapta can be spliced into
      isoforms with between four and six tubulin-binding repeats (4R-6R), while maptb
      is mainly spliced into 3R isoforms. Expression of both genes is observed
      predominantly in the developing central nervous system. A particularly large
      isoform of maptb is specifically expressed in the trigeminal ganglion and in
      dorsal sensory neurons of the spinal cord. Changes in the subcellular ratio of 3R
      and 4R isoforms can have pathological consequences in mammals. The predominant
      production of 4R-6R isoforms from mapta and of 3R isoforms from maptb suggests
      that zebrafish embryos will be a useful tool with which to study the discrete
      functions and interactions of the 3R and 4R MAPT isoforms.

PMID- 19584431
TI  - Stress-induced tau phosphorylation: functional neuroplasticity or neuronal
      vulnerability?
AB  - Abnormally phosphorylated tau protein is a key component of the pathology seen in
      neurodegenerative tauopathies, such as Alzheimer's disease (AD). Despite its
      association with disease, tau phosphorylation (tau-P) also plays an important
      role in neuroplasticity, such as dendritic/synaptic remodeling seen in the
      hippocampus in response to environmental challenges, such as stress. To define
      the boundaries between neuroplasticity and neuropathology, studies have attempted
      to characterize the paradigms, stimuli, and signaling intermediates involved in
      stress-induced tau-P. Supporting an involvement of stress in AD are data
      demonstrating alterations in stress pathways and peptides in the AD brain and
      epidemiological data implicating stress exposure as a risk factor for AD. In this
      review, the question of whether stress-induced tau-P can be used as a model for
      examining the relationship between functional neuroplasticity and neuronal
      vulnerability will be discussed.

PMID- 19584430
TI  - Effects of stress and stress hormones on amyloid-beta protein and plaque
      deposition.
AB  - Growing evidence indicates that physical and psychosocial stressors, in part
      acting through the hypothalamic-pituitary-adrenal (HPA) axis, may accelerate the
      process of Alzheimer's disease (AD). In this review, we summarize recent research
      related to the effects of stress and stress hormones on the various disease
      process elements associated with AD. Specifically, we focus on the relationships
      among chronic stressors, HPA axis activity, amyloid-beta protein, and amyloid
      beta plaque deposition in mouse models of AD. The potential mechanisms by which
      stress and stress-related components, especially corticotrophin-releasing factor
      and its receptors, influence the pathogenesis of AD are discussed.

PMID- 19584433
TI  - Absence of ApoE upregulates murine brain ApoD and ABCA1 levels, but does not
      affect brain sterol levels, while human ApoE3 and human ApoE4 upregulate brain
      cholesterol precursor levels.
AB  - Apolipoprotein E (apoE) is a regulator of peripheral cholesterol homeostasis, and
      the apoE-isoform E4 is a major risk factor for the development of Alzheimer's
      disease (AD). Accumulating evidence suggests a key role for aberrant cholesterol
      metabolism in AD. We hypothesized that apoE-deficiency in mice not only affects
      cholesterol homeostasis in the periphery, but also in the brain, and that this
      can be restored by astrocyte-specific expression of human apoE3, but not apoE4.
      Using gas-chromatography mass-spectrometry, we found that absence of apoE in mice
      does not affect brain cholesterol homeostasis although serum sterol levels
      increase dramatically, especially when the apoE-knockout mice are fed a high fat
      diet. We provide evidence suggesting that apoD and the ATP-binding Cassette
      Transporter A1 (ABCA1) play a compensatory role in the apoE-deficient brain.
      Surprisingly, astrocyte-specific expression of human apoE3 or apoE4 in brains of
      apoE-knockout mice significantly increases brain levels of cholesterol and its
      precursors compared to control mice, indicative of an increased cholesterol
      synthesis rate in the brain. This increase is independent of the apoE-isoform,
      suggesting that the detrimental effect of apoE4 on the pathogenesis of AD is
      unlikely to be due to an apoE-isoform effect on brain cholesterol homeostasis.

PMID- 19584434
TI  - Regulation of the physiological function and metabolism of AbetaPP by AbetaPP
      binding proteins.
AB  - Amyloid-beta protein precursor (AbetaPP) is a receptor-like, type-I membrane
      protein that plays a central role in the pathogenesis of Alzheimer's disease. The
      cytoplasmic domain of AbetaPP is important for the metabolism and physiological
      functions of AbetaPP and contains a GYENPTY motif that interacts with proteins
      that contain a phosphotyrosine binding (PTB) domain such as X11/Mint, FE65, and
      the JIP family of proteins. X11 and X11-like proteins are neuronal adaptor
      proteins involved in presynaptic function and the intracellular trafficking of
      proteins. Recent studies in X11s knockout mice confirmed findings from in vitro
      studies that X11 proteins affect AbetaPP metabolism and the generation of amyloid
      beta peptide. FE65 proteins are involved in transactivation in coordination with
      the intracellular domain fragment of AbetaPP, and/or in cellular responses to DNA
      damage. Neurodevelopmental defects observed in FE65s double knockout mice suggest
      that FE65 proteins cooperate with AbetaPP to play a role in neuronal cytoskeletal
      regulation. c-Jun N-terminal kinase (JNK) interacting protein-1 (JIP-1), a
      scaffolding protein for the JNK kinase cascade, has been suggested to mediate the
      intracellular trafficking of AbetaPP by molecular motor kinesin-1. This article
      reviews some of the recent findings regarding the regulation of physiological
      function and metabolism of AbetaPP by AbetaPP binding proteins.

PMID- 19584435
TI  - Reexamining Alzheimer's disease: evidence for a protective role for amyloid-beta
      protein precursor and amyloid-beta.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease
      characterized clinically by cognitive decline and pathologically by the
      accumulation of amyloid-beta-containing senile plaques and neurofibrillary
      tangles. A great deal of attention has focused, focused on amyloid-beta as the
      major pathogenic mechanism with the ultimate goal of using amyloid-beta lowering
      therapies as an avenue of treatment. Unfortunately, nearly a quarter century
      later, no tangible progress has been offered, whereas spectacular failure tends
      to be the most compelling. We have long contended, as has substantial literature,
      that proteinaceous accumulations are simply downstream and, often, endstage
      manifestations of disease. Their overall poor correlation with the level of
      dementia, and their presence in the cognitively intact is evidence that is often
      ignored as an inconvenient truth. Current research examining amyloid oligomers,
      therefore, will add copious details to what is, in essence, a reductionist
      distraction from upstream pleiotrophic processes such as oxidative stress, cell
      cycle dysfunction, and inflammation. It is now long overdue that the
      neuroscientists avoid the pitfall of perseverating on "proteinopathies'' and
      recognize that the continued targeting of end stage lesions in the face of
      repeated failure, or worse, is a losing proposition.

PMID- 19584436
TI  - Complexes of amyloid-beta and cystatin C in the human central nervous system.
AB  - A role for cystatin C (CysC) in the pathogenesis of Alzheimer's disease (AD) has
      been suggested by the genetic linkage of a CysC gene (CST3) polymorphism with
      late-onset AD, the co-localization of CysC with amyloid-beta (Abeta) in AD
      brains, and binding of CysC to soluble Abeta in vitro and in mouse models of AD.
      This study investigates the binding between Abeta and CysC in the human central
      nervous system. While CysC binding to soluble Abeta was observed in AD patients
      and controls, a SDS-resistant CysC/Abeta complex was detected exclusively in
      brains of neuropathologically normal controls, but not in AD cases. The
      association of CysC with Abeta in brain from control individuals and in
      cerebrospinal fluid reveals an interaction of these two polypeptides in their
      soluble form. The association between Abeta and CysC prevented Abeta accumulation
      and fibrillogenesis in experimental systems, arguing that CysC plays a protective
      role in the pathogenesis of AD in humans and explains why decreases in CysC
      concentration caused by the CST3 polymorphism or by specific presenilin 2
      mutations can lead to the development of the disease. Thus, enhancing CysC
      expression or modulating CysC binding to Abeta have important disease-modifying
      effects, suggesting a novel therapeutic intervention for AD.

PMID- 19584437
TI  - Ginseng for cognitive function in Alzheimer's disease: a systematic review.
AB  - The objective of this review is to assess the clinical evidence for or against
      ginseng as a treatment for Alzheimer's disease (AD). We searched 20 databases
      from their inception to January 2009 and included all randomized clinical trials
      (RCTs) of any type of Panax ginseng to treat human patients suffering from AD.
      Methodological quality was assessed using the Jadad score. Two RCTs met all
      inclusion criteria. They assessed the effectiveness of ginseng as an adjunct to
      drug therapy on cognitive function compared with conventional drug therapy. Their
      results suggested significant effect in favor of ginseng on the Mini-Mental
      Status Examination (n = 174, weight mean difference (WMD), 1.85; 95% confidence
      intervals, CIs 0.88 to 2.82, P = 0.0002) and on the Alzheimer's Disease
      Assessment Scale (ADAS)-cognitive (n = 174, WMD, 3.09; 95% CIs 1.08 to 5.09, P =
      0.003). Both of these studies are burdened with serious methodological
      limitations. In conclusion, the evidence for ginseng as a treatment of AD is
      scarce and inconclusive. Further rigorous trials seem warranted.

PMID- 19584438
TI  - Glial cell-line derived neurotrophic factor (GDNF) concentrations in
      cerebrospinal fluid and serum of patients with early Alzheimer's disease and
      normal controls.
AB  - As neurotrophic factors play an important role in development and maintenance of
      global central nervous system (CNS) function, we supposed that glial cell-line
      derived neurotrophic factor (GDNF), which has been extensively studied for its
      survival promoting effects especially concerning catecholaminergic neurons, also
      plays a significant role in neurodegenerative disease characterized mainly by
      damage of cholinergic CNS neurons like AD. Here we compared GDNF concentrations
      in serum and cerebrospinal fluid (CSF) of patients with probable Alzheimer's
      disease (AD) and normal controls (NC). While GDNF concentrations in CSF were
      significantly increased in patients with AD (291.7 +/- 85.8 pg/ml) compared with
      NC subjects (218.7 +/- 93.3 pg/ml, p = 0.012), GDNF concentration of AD patients
      (486.5 +/- 72.3 pg/ml) in serum were significantly decreased compared with the NC
      group (711.5 +/- 186.5 pg/ml, p < 0.001). Increased GDNF in CSF of AD might be
      due to an upregulated expression in CNS as an adaptive process of the impaired
      brain to enhance neurotrophic support at least in early stages of disease and/or
      impairment of CSF turnover. Decreased serum concentration of GDNF might be
      related to altered function of the blood brain barrier thus disturbing clearance
      or facilitating passover of potentially harmful metabolites.

PMID- 19584439
TI  - Astrocyte function is modified by Alzheimer's disease-like pathology in aged
      mice.
AB  - Alzheimer's disease (AD) may affect all cell types in the central nervous system.
      Astrocytes have rarely been investigated in the aged brain and the role of
      astrocytes in AD is poorly understood. In this study, we used acute brain slices
      from an amyloid-beta overexpressing double transgenic mouse line where astrocytes
      express the enhanced green fluorescent protein under the control of the glial
      fibrillary acidic protein promoter. Using the patch-clamp technique, we analyzed
      cell coupling and glutamate reactivity, two main features of astrocytes, in the
      living tissue of aged mice in an AD mouse model. We found large astrocytic
      networks in the aged (20 to 27 months) transgenic animals in the neocortex, but
      not in the hippocampus. In contrast, coupling was low in all brain regions of
      aged control mice. We furthermore noticed significant changes in the responses of
      astrocytes to glutamate. The expression of functional glutamate transporters and
      AMPA/kainate-type glutamate receptors increases in the amyloid-beta protein
      precursor overexpressing mice. Thus, exposure to amyloid-beta leads to altered
      astrocyte properties and this change might be beneficial to maintain synaptic
      function.

PMID- 19584440
TI  - Alzheimer's disease selective vulnerability and modeling in transgenic mice.
AB  - Neurodegenerative diseases are characterized by 'hot spots' of degeneration. The
      regions of primary vulnerability vary between different neurodegenerative
      diseases. Within these regions, some neurons are lost whereas others that are
      morphologically indiscriminate survive. The enigma of this selective
      vulnerability is tightly linked to two fundamental problems in the neurosciences.
      First, it is not understood how many neuronal cell types make up the mammalian
      brain; estimates are in the order of more than a thousand. Second, the mechanisms
      by which some nerve cells undergo functional impairment followed by degeneration
      while others do not, remain elusive. Understanding the basis for this selective
      vulnerability has significant implications for understanding the pathogenesis of
      disease and for developing treatments. Here, we review what is known about
      selective vulnerability in Alzheimer's disease, frontotemporal dementia, and
      Parkinson's disease. We suggest, since transgenic animal models of disease
      reproduce aspects of selective vulnerability, that these models offer a valuable
      system for future investigations into the physiological basis of selective
      vulnerability.

PMID- 19584441
TI  - The Multidimensional Prognostic Index (MPI), based on a comprehensive geriatric
      assessment predicts short- and long-term mortality in hospitalized older patients
      with dementia.
AB  - Aim of this study was to evaluate the usefulness of a Multidimensional Prognostic
      Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) for predicting
      mortality risk in older patients with dementia. The present was a retrospective
      study with a year of follow-up that included 262 patients aged 65 years and older
      with a diagnosis of dementia. A standardized CGA that included information on
      clinical, cognitive, functional, and nutritional aspects, as well as comorbidity,
      medications, and social support network, was used to calculate MPI. The
      predictive value of the MPI for all-cause mortality over 1 month, 6 months, and
      12 months of follow-up was evaluated. Higher MPI values were significantly
      associated with higher mortality at 1 month (MPI-1, low risk = 0%, MPI-2,
      moderate risk = 5.2%, MPI-3, severe risk = 13.7%; p < 0.002), 6-months (MPI-1 =
      2.7%, MPI-2 = 11.2%, MPI-3 = 28.8%; p < 0.001), and 12-months (MPI-1 = 2.7%, MPI
      2 = 18.2%, MPI-3 = 35.6%; p < 0.001) of follow-up. The discrimination of the MPI
      was also good, with areas under the ROC curves of 0.77 (sensitivity = 82.9%,
      specificity = 66.0%, with a cut off value > 0.16) at 12-months of follow up. In
      conclusion, the MPI, calculated from information collected in a standardized CGA,
      accurately stratified hospitalized elderly patients with dementia into groups at
      varying risk of short- and long-term mortality.

PMID- 19584443
TI  - Novel T719P AbetaPP mutation unbalances the relative proportion of amyloid-beta
      peptides.
AB  - A novel missense mutation (T719P) in the amyloid-beta protein precursor (AbetaPP)
      gene was discovered in a 46-year old patient affected by early onset familial
      Alzheimer's disease. Using surface enhanced laser desorption/ionization mass
      spectrometry (SELDI-TOF MS), we determined mass profiles of amyloid-beta peptides
      (Abeta) in cerebrospinal fluid (CSF) of the AbetaPP mutated patient, healthy
      control subjects (n = 10), and of two subjects carrying mutations in presenilins
      genes (PS) (i.e., PS1 P117L and PS2 T122R): seven different C-terminally and
      three N-terminally truncated Abeta peptides were found in CSF. The investigated
      AbetaPP as well as PS mutations were associated with an overall reduction of
      Abeta species, except for Abeta(10-40). Interestingly, the AbetaPP T719P mutation
      unbalanced the relative proportion of Abeta peptides with a reduction of Abeta(1
      40) and Abeta(1-42) paralleled by an increase of Abeta(1-38) and Abeta(10-40).
      Despite the specific neuropeptidomic phenotype associated with the AbetaPP T719P
      mutation, the enrichment in Abeta(10-40) paralleled by depletion of Abeta(1-42)
      seems to be a common theme in familial AD. The AbetaPP T719P mutation is of
      particular interest because it is the only mutation located in close proximity to
      the AbetaPP epsilon-cleavage site.

PMID- 19584444
TI  - Amyloid-beta42 plasma levels are elevated in amnestic mild cognitive impairment.
AB  - Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of
      Alzheimer's disease (AD). We measured plasma levels of amyloid-beta40 (Abeta40)
      and Abeta42 in 191 subjects with aMCI. Seventy-nine of them were clinically
      followed for two years. In the total cohort of aMCI cases, the average level of
      Abeta42, as well as the Abeta42/Abeta40 ratio, was significantly higher than
      those of the 102 cognitively normal age-matched subjects. The aMCI cases that
      converted to probable AD within 2 years had higher levels of Abeta42 and, to a
      lesser extent, Abeta40 than the stable cases. However the large variability of
      measured values indicates that plasma Abeta is not a suitable marker of incipient
      AD.

PMID- 19584442
TI  - Lifespan profiles of Alzheimer's disease-associated genes and products in monkeys
      and mice.
AB  - Alzheimer's disease (AD) is characterized by plaques of amyloid-beta (Abeta)
      peptide, cleaved from amyloid-beta protein precursor (AbetaPP). Our hypothesis is
      that lifespan profiles of AD-associated mRNA and protein levels in monkeys would
      differ from mice and that differential lifespan expression profiles would be
      useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA,
      AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a
      transcriptional regulator of the AbetaPP gene, specificity protein 1 (SP1), and
      the beta amyloid precursor cleaving enzyme (BACE1). In mice, AbetaPP and SP1 mRNA
      and their protein products were elevated late in life; Abeta levels declined in
      old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while
      protein products and Abeta levels rose. Proteolytic processing in both species
      did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels
      coordinate, but an inverse relationship exists with corresponding protein
      products as well as Abeta levels. Comparison of human DNA and mRNA sequences to
      monkey and mouse counterparts revealed structural features that may explain
      differences in transcriptional and translational processing. These findings are
      important for selecting appropriate models for AD and other age-related diseases.

PMID- 19584445
TI  - The effects of enhanced zinc on spatial memory and plaque formation in transgenic
      mice.
AB  - There is considerable evidence suggesting that metals play a central role in the
      pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals
      may both precipitate and potentiate an Alzheimer's disease phenotype. Despite
      this, there remain few studies that have examined the behavioral consequences of
      elevated dietary metals in wild type and Alzheimer's disease animals. To further
      investigate this in the current study, two separate transgenic models of AD
      (Tg2576 and TgCRND8), together with wild type littermates were administered 10
      ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both
      pre- and postnatally until 11 months of age, while TgCRND8 animals were treated
      for five months following weaning. Behavioral testing, consisting of "Atlantis"
      and "moving" platform versions of the Morris water maze, were conducted at the
      end of the study, and tissues were collected for immunohistochemical analysis of
      amyloid-beta burden. Our data demonstrate that the provision of a zinc-enriched
      diet potentiated Alzheimer-like spatial memory impairments in the transgenic
      animals and was associated with reduced hippocampal amyloid-beta plaque deposits.
      Zinc-related behavioral deficits were also demonstrated in wild type mice, which
      were sometimes as great as those present in the transgenic animals. However, zinc
      related cognitive impairments in transgenic mice were greater than the summation
      of zinc effects in the wild type mice and the transgene effects.

PMID- 19584446
TI  - A study of the SORL1 gene in Alzheimer's disease and cognitive function.
AB  - Several studies have investigated the role of the neuronal sortilin-related
      receptor (SORL1) gene in Alzheimer's disease (AD), but findings have been
      inconsistent. We conducted a study of 7 single nucleotide polymorphisms (SNPs),
      rs668387, rs689021, rs641120, rs1699102, rs3824968, rs2282649, and rs1010159, in
      the SORL1 gene that were associated to AD in previous studies. We tested for
      association with AD and cognitive function in 6741 participants of the Rotterdam
      Study and in 2883 individuals from the Erasmus Rucphen Family study. We performed
      meta-analyses on AD using our data together with those of previous studies
      published prior to September 2008 in Caucasians. Further, we studied up to 76
      SNPs in a 400 kb region within and flanking the gene to evaluate the evidence
      that other genetic variants are associated with AD or cognitive function. There
      was no significant evidence for association between SORL1 SNPs and incident AD
      patients in the Rotterdam Study. In a meta-analysis of our data with those of
      others, six out of seven SNPs attained borderline significance. However, removal
      of the first study reporting association from the meta-analysis resulted in non
      significant odds ratios for all SNPs. SNPs rs668387, rs689021, and rs641120 were
      associated with cognitive function in non-demented individuals at borderline
      statistical significance in two independent Dutch cohorts, but in the opposite
      direction. Testing for association using dense SNPs in the SORL1 gene did not
      reveal significant association with AD, or with cognitive function when adjusting
      for multiple testing. In conclusion, our data do not support the hypothesis that
      genetic variants in SORL1 are related to the risk of AD.

PMID- 19584448
TI  - Iron regulatory protein 2 is involved in brain copper homeostasis.
AB  - Trace metal homeostasis is tightly controlled in the brain, as even a slight
      dysregulation may severely impact normal brain function. This is especially
      apparent in Alzheimer's disease, where brain homeostasis of trace metals such as
      copper and iron is dysregulated. As it is known that iron and copper metabolism
      are linked, we wanted to investigate if a common mechanism could explain the
      increase in iron and decrease in copper seen in Alzheimer's disease brain.
      Amyloid-beta protein precursor (AbetaPP) has been implicated in copper efflux
      from the brain. Furthermore, it was shown that iron regulatory proteins (IRP),
      which regulate iron homeostasis, can block AbetaPP mRNA translation. In a
      correlative study we have therefore compared brain regional copper levels and
      AbetaPP expression in mice with a targeted deletion of IRP2-/-. Compared with
      controls, six week old IRP2-/- mice had significantly less brain copper in the
      parietal cortex, hippocampus, ventral striatum, thalamus, hypothalamus, and whole
      brain, while AbetaPP was significantly upregulated in the hippocampus (p < 0.05)
      and showed a trend toward upregulation in the thalamus (p < 0.1). This is the
      first study to demonstrate that iron regulatory proteins affect brain copper
      levels, which has significant implications for neurodegenerative diseases.

PMID- 19584449
TI  - Increased inflammatory response both in brain and in periphery in presenilin 1
      and presenilin 2 conditional double knock-out mice.
AB  - It has been reported that conditional double knockout of presenilin-1 and
      presenilin-2 in forebrain of mice (dKO mice) induce symptoms most analogous to
      that of neurodegenerative diseases, especially Alzheimer's disease, however,
      there is no deposition of extra amyloid-beta (Abeta(40) or Abeta(42)) in dKO
      brain. In the present study, we thoroughly measured the inflammatory response in
      dKO mice, which is another global symptom in neurodegenerative diseases. We
      demonstrated that glial cells were dramatically activated from early age (3
      months) in dKO brain when compared with control mice. In addition, complement
      C1qalpha and C4, the key components in the classical complement pathway, were
      also stimulated in dKO mice brain. Antibody array and ELISA analysis indicated
      that cytokine and chemokine levels were also significantly increased in dKO
      brain. Moreover, we found that leukocytes were elevated beginning at 6 months of
      age, and multiple inflammatory mediators changed in dKO mice serum at 9 months,
      showing that the inflammatory responses gradually expanded to systemic tissue.
      These findings confirm that presenilins double knockout results in robust
      inflammatory response both in brain and in periphery and suggest that dKO mice
      may be useful to further understand the effects of inflammation on the
      pathological processes of neurodegenerative diseases.

PMID- 19584447
TI  - Impact of APOE on the healthy aging brain: a voxel-based MRI and DTI study.
AB  - Neuroimaging studies of apolipoprotein E (ApoE4) have implicated its association
      with brain atrophy in Alzheimer's disease. To date, few studies have used
      automated morphological analysis techniques to assess ApoE4-related brain
      structure change in both gray and white matter in nondemented older adults.
      Nondemented (CDR = 0, n = 53) subjects over 60 had MRI, diffusion tensor imaging,
      and neurocognitive assessments. We assessed differences in cognition and brain
      structure associated with ApoE4 genetic variation using voxel-based morphometry
      techniques, and tract-based spatial statistics of fractional anisotropy change.
      In nondemented older adults with the E4 allele, cognitive performance was
      reduced, and atrophy was present in the hippocampus and amygdala compared to
      ApoE4 negative participants. We also report that E4 carriers have decreased
      fractional anisotropy in the left parahippocampal gyrus white matter. In
      conclusion, the presence of an ApoE4 allele in nondemented older adults is
      associated with decreases in cognition and gray and white matter changes in the
      medial temporal cortex. Overall we provide further evidence of the effects of
      genetic variance related to imaging and cognitive measures of risk for
      Alzheimer's disease.

PMID- 19584450
TI  - Differential patterns of implicit emotional processing in Alzheimer's disease and
      healthy aging.
AB  - Implicit memory for emotional facial expressions (EFEs) was investigated in young
      adults, healthy old adults, and mild Alzheimer's disease (AD) patients. Implicit
      memory is revealed by the effect of experience on performance by studying
      previously encoded versus novel stimuli, a phenomenon referred to as perceptual
      priming. The aim was to assess the changes in the patterns of priming as a
      function of aging and dementia. Participants identified EFEs taken from the
      Facial Action Coding System and the stimuli used represented the emotions of
      happiness, sadness, surprise, fear, anger, and disgust. In the study phase,
      participants rated the pleasantness of 36 faces using a Likert-type scale.
      Subsequently, the response to the 36 previously studied and 36 novel EFEs was
      tested when they were randomly presented in a cued naming task. The results
      showed that implicit memory for EFEs is preserved in AD and aging, and no
      specific age-related effects on implicit memory for EFEs were observed. However,
      different priming patterns were evident in AD patients that may reflect
      pathological brain damage and the effect of stimulus complexity. These findings
      provide evidence of how progressive neuropathological changes in the temporal and
      frontal areas may affect emotional processing in more advanced stages of the
      disease.

PMID- 19584451
TI  - Impact of APOE epsilon4 on the cognitive performance of a sample of non-demented
      Puerto Rican nonagenarians.
AB  - APOE epsilon4 is a major risk factor for Alzheimer's disease. It has also been
      associated with cognitive impairment and cognitive decline in young-olds, but the
      impact of the epsilon4 allele on cognitive function in very late life is still
      unclear. The object of this study was to evaluate the association of the epsilon4
      allele of APOE with the cognitive performance of a sample of non-demented oldest
      olds. Eighty-seven Spanish-speaking Puerto Rican non-demented nonagenarians were
      administered a complete neuropsychological assessment and provided a blood sample
      used for APOE genotyping. A factor analysis generated two factors: 1) verbal
      memory; and 2) visuo-spatial, naming and attention tasks, accounting for 43.6% of
      the overall variance in the 13 original neuropsychological variables. The
      multivariate analysis reflected, after controlling for gender, education, and
      age, the APOE epsilon4 carriers performed better in overall cognition (both
      factors analyzed together) than non-carriers (T<formula>;{2}</formula> = 0.082,
      F(2,80) = 3.289, p = 0.042). Neither gender nor the gender by APOE epsilon4
      status interaction was associated with differences in cognition. In conclusion,
      the results of this study suggest that, among these Puerto Rican non-demented
      nonagenarians, being an APOE epsilon4 allele carrier is associated with better
      cognition.

PMID- 19584453
TI  - Neurological soft signs in nursing home residents with Alzheimer's disease.
AB  - Neurological soft signs (NSS), i.e., minor motor and sensory changes, are a
      common feature in psychiatric disorders related to brain changes. Nevertheless,
      they have rarely been investigated in patients with Alzheimer's disease (AD). NSS
      were examined in 104 nursing home residents with AD with respect to dementia
      severity, neuropsychiatric symptoms, and Parkinsonian signs as well as potential
      medication effects. 16 cognitively unimpaired residents served as a control
      group. NSS scores were significantly higher in residents with AD and were
      associated with both severity of cognitive deficits and non-cognitive symptoms,
      in particular apathy, but neither with Parkinsonian signs nor with antipsychotic
      medication. Our results demonstrate that NSS increase with progression of AD and
      one may hypothesize that they are linked to degenerative cerebellar changes. NSS
      in AD are clinically significant and thus, besides other neurological symptoms,
      are to be considered in diagnostics and therapy.

PMID- 19584452
TI  - Lesion-induced hippocampal plasticity in transgenic Alzheimer's disease mouse
      models: influences of age, genotype, and estrogen.
AB  - We have studied entorhinal cortex lesion-induced sprouting in the hippocampus in
      young, adult, and aged control and transgenic Alzheimer's disease model mice. The
      entorhinal cortex was unilaterally, partially lesioned, and four weeks later the
      subsequent axonal sprouting in dentate gyrus was analyzed. Our data demonstrate
      that young and adult, control and amyloid-beta protein precursor
      (AbetaPP)/presenilin 1 (PS1) mice display a significantly increased density of
      staining for synaptophysin in dentate gyrus, indicative of axonal sprouting.
      However, whereas young and adult mice demonstrate sprouting, aged mice (control
      and AbetaPP/PS1) do not show a significant upregulation of synaptophysin staining
      following the lesions. In contrast, aged mice overexpressing PS1 show an
      increased regenerative response compared to age-matched control mice and mice
      overexpressing AbetaPP which do not show sprouting. Further, the data demonstrate
      that a significant Abeta load in the dentate gyrus does not prevent axonal
      sprouting. Lastly, only aged mice show significant shrinkage of the molecular
      layer of dentate gyrus following entorhinal cortex lesions. Further, adult
      ovariectomized females (control and AbetaPP/PS1) are significantly reduced in
      their plasticity following lesions. Taken together, the data indicate that
      amyloid-beta deposits do not negatively impact plasticity in the brain and that
      overexpression of AbetaPP is not beneficial, but that normal estrogen levels are
      beneficial for plasticity.

PMID- 19584454
TI  - Neuropathology and the neuroinflammation idea.
AB  - A role for innate immunity in neurodegenerative diseases is now widely accepted,
      although debate continues over the relative contributions of these processes to
      disease progression and/or to disease amelioration. The idea that microglia and
      cytokines are important in neurodegeneration arose from neuropathological
      observations, especially in Alzheimer's disease. Microglia are invariant
      components of the Abeta plaques of Alzheimer's disease, where they show a waxing
      and waning of numbers, activation state, and cytokine expression during plaque
      progression. This is in contrast to diffuse Abeta deposits sometimes found in
      abundance in the brain of non-demented elderly individuals, which do not contain
      activated microglia. In Alzheimer's disease, plaque-associated astrocytes, which
      also produce paracrine mediators, show a pattern similar to that of microglia;
      and the associated plaque progression is accompanied by progressive damage to and
      loss of adjacent neurons. Further, activated microglia and astrocytes show a
      progressive pattern of association with neurofibrillary tangles. These
      observations, together with known functions of the involved cytokines, originally
      suggested a central role for immunological phenomena in driving disease
      progression in Alzheimer's disease. Further observations have extended these
      ideas to alpha-synuclein-based diseases (Parkinson's disease, dementia with Lewy
      bodies, and multiple system atrophy) as well as other neurodegenerative diseases
      and conditions.

PMID- 19584455
TI  - Heteroplasmy of mitochondrial D310 mononucleotide repeat region in the blood of
      patients with Alzheimer's disease.
AB  - There is increasing evidence of oxidative stress in patients with Alzheimer's
      disease (AD) and mild cognitive impairment (MCI). Because mitochondrial DNA
      (mtDNA) is susceptible to oxidative damage, somatic mtDNA mutations may be
      induced by oxidative stress. Most of the studies examining mitochondrial
      mutations have been performed on postmortem brain tissues of AD patients. This
      study examined peripheral blood samples of AD and MCI patients to determine if
      peripheral mtDNA mutations are associated with these two conditions. A total of
      236 subjects, including 71 AD patients, 84 amnestic MCI patients, 41 cognitively
      normal aging controls, and 40 young controls, were recruited. There was
      heteroplasmy of the mtDNA D310 polycytosine repeat region in 37 of 71 (52.1%) AD
      patients and this was significantly more frequent than in MCI patients (31.0%),
      normal aging (31.7%), and young controls (27.5%). However, subjects with amnestic
      MCI did not have a significantly higher rate of heteroplasmy in D310 than
      cognitively normal elderly subjects. The heteroplasmic alterations of D310 were
      more frequently in subjects with a larger number of polycytosine repetitions.
      Insertion of cytosine was the most common mutation type. The results suggest that
      mutations of mtDNA 310 region are frequently present in the peripheral blood of
      AD patients. Further prospective investigations to determine if MCI subjects with
      D310 mutations develop AD is warranted.

PMID- 19584456
TI  - Global warming and its impact on skin disorders.

PMID- 19584457
TI  - Crusted scabies.
AB  - Crusted scabies is a rare manifestation of scabies characterized by uncontrolled
      proliferation of mites in the skin. In immunocompromised patients, this
      infestation is characterized by crusted lesions. The occurrence of the disease in
      human immunodeficiency virus-infected patients and the widespread use of
      immunosuppressive agents has led to a renewed interest in the disease. Early
      recognition and treatment is necessary to avoid an outbreak of scabies. This
      review highlights the pathogenesis, predisposing factors, clinical features and
      treatment of crusted scabies.

PMID- 19584458
TI  - Dermatitis cruris pustulosa et atrophicans.
AB  - Dermatitis cruris pustulosa et atrophicans (DCPA) is a distinctive type of
      chronic superficial folliculitis, primarily affecting the lower limbs. It is
      characterized by symmetrical follicular pustules of both legs, with cutaneous
      edema, resulting in alopecia, atrophy and scarring. It was first described by
      Clarke, from West Nigeria, in 1952 and well illustrated in his book "Skin
      diseases in the African," under the initial label of "Nigerian shin disease."
      Subsequently, it was described in India as well, in 1964, and continues to be a
      problem in dermatology clinics across the country. It is predominantly a disease
      of men and has a high prevalence in some geographical regions; up to 3-4% in
      Madras, South India. Some unique features that distinguish DCPA from banal
      pustular folliculitis include its peculiar localization to the legs, extreme
      chronicity, resistance to therapy and inevitable alopecia and atrophy of the
      involved skin, with little postinflammatory hyper- or hypopigmentation. Further,
      even in the presence of extensive lesions, there are no systemic features.
      Coagulase-positive Staphylococcus aureus is known to have a role in the etiology
      of DCPA, but the exact etiopathogenesis still needs to be elucidated.
      Immunological postulates such as hypergammaglobulinemia have been put forward to
      explain the chronicity of the condition. A number of therapeutic agents have been
      tried in various studies, including cotrimoxazole, psoralen with ultraviolet A
      (PUVA) therapy, ciprofloxacin, pentoxifylline, rifampicin, dapsone, minocycline
      and mupirocin (topical) with variable success rates. Although a well-recognized
      entity in dermatology clinics in tropical countries, DCPA has received little
      attention in the dermatological literature and has only a few studies to its
      credit. Its unique clinical picture, unclear etiopathogenesis and resistance to
      therapy afford a vast scope for further investigation and study.

PMID- 19584459
TI  - Cutaneous vasculitides: clinico-pathological correlation.
AB  - BACKGROUND: Cutaneous vasculitis presents as a mosaic of clinical and
      histological findings. Its pathogenic mechanisms and clinical manifestations are
      varied. AIMS: To study the epidemiological spectrum of cutaneous vasculitides as
      seen in a dermatologic clinic and to determine the clinico-pathological
      correlation. METHODS: A cohort study was conducted on 50 consecutive patients
      clinically diagnosed as cutaneous vasculitis in the dermatology outdoor;
      irrespective of age, sex and duration of the disease. Based on the clinical
      presentation, vasculitis was classified according to modified Gilliam's
      classification. All patients were subjected to a baseline workup consisting of
      complete hemogram, serum-creatinine levels, serum-urea, liver function tests,
      chest X-ray, urine (routine and microscopic) examination besides antistreptolysin
      O titer, Mantoux test, cryoglobulin levels, antineutrophilic cytoplasmic
      antibodies and hepatitis B and C. Histopathological examination was done in all
      patients while immunofluorescence was done in 23 patients. RESULTS: Out of a
      total of 50 patients diagnosed clinically as cutaneous vasculitis, 41 were
      classified as leukocytoclastic vasculitis, 2 as Heinoch-Schonlein purpura, 2 as
      urticarial vasculitis and one each as nodular vasculitis, polyarteritis nodosa
      and pityriasis lichenoid et varioliforme acuta. Approximately 50% of the patients
      had a significant drug history, 10% were attributed to infection and 10% had
      positive collagen workup without any overt manifestations, while 2% each had
      Wegener granulomatosis and cryoglobulinemia. No cause was found in 26% cases.
      Histopathology showed features of vasculitis in 42 patients. Only 23 patients
      could undergo direct immunofluorescence (DIF), out of which 17 (73.9%) were
      positive for vasculitis. CONCLUSIONS: Leukocytoclastic vasculitis was the
      commonest type of vaculitis presenting to the dermatology outpatient department.
      The workup of patients with cutaneous vasculitis includes detailed history,
      clinical examination and investigations to rule out multisystem involvement
      followed by skin biopsy and DIF at appropriate stage of evolution of lesions.
      Follow up of these patients is very essential as cutaneous manifestations may be
      the forme fruste of serious systemic involvement.

PMID- 19584460
TI  - Comparison of seropositivity of human T lymphotropic virus type 1 in mycosis
      fungoides patients and normal volunteers: a case-control study and review of
      literature.
AB  - BACKGROUND: There have been controversial reports about the possible association
      between mycosis fungoides (MF), its leukemic variant Siotazary syndrome (SS) and
      human T lymphotropic virus type 1 (HTLV-1) in different geographical regions.
      AIMS: The purpose of this study was to explore any association between MF and
      presence of HTLV-1 infection in Iran. METHODS: In a case-control setting, 150
      clinically and histopathologically proven MF patients had been admitted to the
      tertiary referral skin center during a 10-year period and another 150 normal
      volunteers had been compared with each other for the presence of HTLV-1
      infection. Enzyme-linked immunosorbent assay (ELISA) was used to detect
      antibodies against HTLV-1, and positive results were confirmed with western
      blotting. RESULTS: Only three MF patients had HTLV-1 infection, whereas two cases
      of normal subjects had the infection (P > 0.05). The only three seropositive MF
      patients were male and from North-Eastern Iran. CONCLUSION: This study showed
      that MF does not correlate with HTLV-1 infection in Iran.

PMID- 19584461
TI  - Keloids: assessment of effects and psychosocial-impacts on subjects in a black
      African population.
AB  - BACKGROUND: Keloids are vexatious swelling on the skin or the conjuctiva. The
      effects and impacts of these lesions have not been assessed in a keloid endemic
      environment like Nigeria. AIMS: The purpose of this study is to assess the
      psychosocial impact as well as effects of keloids on the subjects in a black
      African population where lesions are commonly seen. METHODS: This is a
      prospective study which assesses the impacts of keloid on keloid patients.
      Consented patients who presented to the Plastic Surgery Clinic of the Lautech
      Teaching Hospital, Osogbo, Nigeria were recruited into the study. A set of
      questionnaires were administered to all consented patients. The administered
      questionnaires were analyzed using SPSS version 10. RESULTS: One hundred and
      thirty one patients were involved in this study. They comprised of 61 males and
      70 females. Most (96.8%) of them had the keloid lesion for more than one year.
      Sixteen (12.2%) of the patients felt that keloids negatively affect their works,
      64 (48.9%) of the patients felt stigmatized by keloids, 28 (56.0%) of them who
      had lesions in conspicuous parts while 24 (46.2%) had lesions in non-conspicuous
      parts. Females (59.1%) felt stigmatized than males. Only 47 (35.8%) of the
      patients believed that keloid swelling limit their social interaction.
      CONCLUSION: Keloids do not appear to have significant negative impacts on keloid
      patients in a keloid-endemic community like a black African population.

PMID- 19584462
TI  - Outcome of dexamethasone-cyclophosphamide pulse therapy in pemphigus: a case
      series.
AB  - BACKGROUND: Pemphigus disorders are a group of serious and potentially life
      threatening diseases affecting skin and/or mucus membranes. Dexamethasone
      cyclophosphamide pulse (DCP) therapy has shown promising results in the
      management of these diseases. AIMS: The objective of the study was to assess the
      outcome of DCP therapy in pemphigus. METHODS: Pemphigus patients who had been
      treated with DCP therapy from 2001 to 2008 were prospectively and retrospectively
      analyzed. RESULTS: A total of 65 pemphigus patients were enrolled. Male to female
      ratio was 1 : 1.82. Mean age of patients was 44.65 +/- 11.85 years with a range
      of 14 to 73 years. Thirty two patients completed phase I, of which 28 (9 in phase
      II, 7 in phase III and 12 in phase III) were maintaining remission and four
      patients relapsed. Relapse was observed only in patients who discontinued or took
      irregular treatment. Six patients were declared cured of disease. Five patients
      died during phase I. Dexamethasone-cyclophosphamide pulse therapy is not
      absolutely free from adverse effects. Most of the immediate side effects were
      expected, tolerable and did not pose any problem in continuing treatment. There
      was a slight increased incidence of weight gain, hypertension, diabetes mellitus,
      cataract and Cushingoid habitus, since most of our patients also received
      additional daily oral steroids. Also, there was a high incidence of secondary
      pyogenic infections of skin lesions and oral candidiasis during phase I.
      Staphylococcus aureus was the commonest bacteria isolated from the pus of skin
      lesions. Most of the alterations in laboratory parameters were transitory or
      correctable, and did not pose a problem in continuing therapy. CONCLUSIONS: DCP
      therapy was found to be effective in inducing and maintaining remission in
      pemphigus, provided the patients receive regular and complete treatment.

PMID- 19584463
TI  - Evaluation of pityriasis versicolor in prisoners: a cross-sectional study.
AB  - BACKGROUND: Pityriasis versicolor (PV) is a mild but recurrent superficial fungal
      infection of stratum corneum. Many predisposing factors such as late teen and
      young adulthood age, tropical and subtropical climate (and to a lesser extent
      temperate climate), immunosuppression, malnutrition, use of oral contraceptives,
      hyperhidrosis, poor hygiene and a few other factors have been proposed for this
      condition. AIM: Regarding these probable and possible risk factors, we felt that
      jail is a unique population which can be affected by this infection and therefore
      we decided to evaluate some aspects of this infection in this population.
      METHODS: In this cross-sectional study in male prisoners of Bandarabbas city, 230
      prisoners were randomly selected. One hundred and five (45.67%) of them were
      diagnosed to be infected. They were also evaluated regarding age, duration of
      being imprisoned, skin color, site of lesion and its pigmentation change and any
      concomitant clinical manifestation such as pruritus, burning or cebure. Chi
      square test or Fisher's exact test was used for data analysis. RESULTS: Mean age
      of infected population was 31.62 +/- 8.67 years while peak incidence of PV was in
      28-32 years age group. The most common color change was hypopigmentation. No case
      of PV hyperpigmentation was seen. We could not also observe any association
      between skin color and duration of being imprisoned with the frequency of
      infection. CONCLUSION: There seems to be no difference between pattern of
      infection in the general population and prisoners' population in the aspects
      evaluated.

PMID- 19584464
TI  - Agent-based model of laser hair removal: a treatment optimization and patient
      education tool.
AB  - BACKGROUND: Tracking of various parameters associated with laser hair removal is
      tedious and time consuming. The currently available mathematical models are not
      simple enough for physicians to be used as a treatment optimization and patient
      education tool. AIM: The aim of the study was to develop a mathematical model for
      laser hair removal using agent-based modeling and to make a user-friendly
      simulation environment. METHODS: The model was created using NetLogo. The hairs
      were modeled as agents oscillating between anagen and telogen. The variables were
      assigned based on published data whenever possible and the various paths the
      agent could take were coded as conditional statements. The improvement was
      assessed using an arbitrary index which takes into account the mean diameter and
      pigmentation along with the number and length of hairs visible above the surface.
      Few of the commonly encountered scenarios were simulated using the model.
      RESULTS: The model is made freely available online
      (http://www.gulfdoctor.net/model/lhr.htm). Limited number of simulations
      performed indicated that an eight-week gap between laser sessions may be more
      effective than a four-week gap. CONCLUSIONS: The simulation provides a reliable
      tool for treatment optimization and patient education as obtaining relevant
      clinical data is slow and labor-intensive. Its visual interface and online
      availability makes it useful for everyday use.

PMID- 19584465
TI  - Linear morphea with secondary mucinosis.
AB  - Secondary mucin deposition in the skin is a common feature of lupus erythematosus
      and dermatomyositis. In scleroderma, it occurs uncommonly or in small amount. We
      describe a 7-year-old boy with progressive, linear, bound-down plaques involving
      the thighs, lower abdomen and back with no systemic involvement. Histopathology
      showed features of scleroderma with abundant mucin deposition in the reticular
      dermis. This report highlights excessive mucin deposition in lesions of morphea.

PMID- 19584466
TI  - Kaposi's sarcoma: a presenting manifestation of HIV infection in an Indian.
AB  - Kaposi's sarcoma (KS) is a multifocal neoplastic proliferation of endothelial
      cells predominantly involving skin and other organs. HIV-associated Kaposi's
      sarcoma has been rarely reported from India. A 38-year-old male presented with
      persistent swelling on the left lower limb for one year along with multiple
      erythematous to dusky papules and plaques of one and half months duration and
      swelling and black discoloration of right lower limb for one month. Cutaneous
      examination revealed numerous skin colored and erythematous papules and plaques
      distributed on the left lower limb on the anteromedial aspect and verrucous
      plaque on the left sole. Multiple erythematous, grouped papules were present over
      the soft palate. Skin biopsy showed numerous slit like spaces dissecting into the
      collagen of the upper and mid-dermis along with 'promontory sign' suggestive of
      Kaposi's sarcoma. Patient was found to be HIV-positive by ELISA test.

PMID- 19584467
TI  - Primary systemic amyloidosis: three different presentations.
AB  - Primary systemic amyloidosis is a rare disease. We report three cases of primary
      systemic amyloidosis, one case with multiple myeloma and two cases without any
      hematological abnormality. Purpuric lesions were the only presenting symptoms of
      the patient with multiple myeloma and only on investigation, myeloma was
      detected. Bone marrow biopsy and serum and urine electrophoresis were normal in
      remaining two cases. These two patients presented with typical waxy lesions on
      face. Cutis verticis gyrata was present in one case and carpal tunnel syndrome
      was seen in other case as an additional diagnostic clue. Macroglossia was present
      in all three cases. Diagnosis was confirmed in all three cases by biopsy using
      haematoxylin and eosin staining and Congo red staining. Polarized microscopy was
      not done because of unavailability.

PMID- 19584468
TI  - Three cases of Dowling Degos disease in two families.
AB  - Dowling Degos disease is a rare condition inherited as autosomal dominant trait
      characterized by numerous, asymptomatic, symmetrical, progressive, small, round
      pigmented macules over axillae and groins, face, neck, arms and trunk, scattered
      comedo-like lesions (dark dot follicles) and pitted acneiform scars.
      Histopathology is diagnostic. We are hereby reporting three cases of Dowling
      Degos disease belonging to two families. Our first and second case belonged to
      the same family, whereas our third case belonged to different family. In our
      series, all the patients had onset after puberty. All three cases had reticulate
      pigmentation over face and/or flexures, black comedones and follicular pits. On
      histopathological examination of the skin biopsy taken from the lesion over the
      back, all these patients showed classical histopathological features of Dowling
      Degos disease. We feel that one should investigate the patient presenting with
      reticulate pigmentation over the face and flexures with blackish comedone-like
      lesions, because histopathological features of this condition are unmistakable.

PMID- 19584469
TI  - Moist flat-topped raised genital lesions in late pregnancy.

PMID- 19584470
TI  - Clinico-epidemiological profile of cutaneous manifestations among human
      immunodeficiency virus positive patients in the sub-Himalayan region.

PMID- 19584471
TI  - Spider nevi and chronic liver disease.

PMID- 19584472
TI  - Correlation of the severity of cutaneous rosacea with ocular rosacea.

PMID- 19584473
TI  - Giant nevus lipomatosus cutaneous superficialis.

PMID- 19584474
TI  - Nifedipine-induced acute generalized exanthematous pustulosis in a case of acute
      glomerulonephritis.

PMID- 19584475
TI  - Proximal subungual onychomycosis caused by Aspergillus flavus in a HIV-positive
      patient.

PMID- 19584476
TI  - Acral dyschromatosis with developmental regression and dystonia in a seven-year
      old child: dyschromatosis symmetrica hereditaria variant or a new syndrome?

PMID- 19584477
TI  - Ross syndrome.

PMID- 19584478
TI  - A mini-outbreak of cutaneous anthrax in Vizianagaram District, Andhra Pradesh,
      India.

PMID- 19584479
TI  - Hemorrhagic cystitis following dexamethasone:cyclophosphamide pulse therapy.

PMID- 19584480
TI  - Dermatomal giant nevus unius lateralis.

PMID- 19584481
TI  - Leflunomide.

PMID- 19584482
TI  - Sutures and suturing techniques in skin closure.

PMID- 19584484
TI  - Asymptomatic yellowish papules and plaques over flexures.

PMID- 19584483
TI  - Linear nodules along the arm.

PMID- 19584485
TI  - Multiple angiokeratomas on the breast.

PMID- 19584486
TI  - A retrospective analysis of adverse events in the elderly in a tertiary referral
      center in Mumbai (Bombay), India.
AB  - BACKGROUND: Adverse events (AEs) account for significant morbidity and mortality
      in elderly. Inappropriate medication usage has been regarded as an important
      factor contributing to AEs in them. Beers criteria are a set of standard criteria
      for guiding drug prescription in elderly. OBJECTIVE: To estimate the burden of
      AEs in the elderly in India and use of Beers criteria for assessing
      appropriateness of drug prescription in them. MATERIALS AND METHODS: Data on AEs
      collected by our tertiary referral center for the years 2005 and 2006 was
      analyzed. The term 'elderly individuals' was defined as those aged >or=58 years.
      An AE was defined as any untoward medical occurrence with a medicinal product in
      a patient or a clinical investigation, whether or not causally related. RESULTS:
      In 2005, 321 AEs were reported, and in 2006 there were 673. Of them, those in the
      elderly constituted 60 (18.9%) and 44 (11.8%) AEs in the 2 years, respectively.
      About 7 (11.6%) of the AEs in elderly in 2005 were due to medications not
      fulfilling Beers criteria but none in 2006. Two thirds of the AEs in both years
      were found to be due to antidiabetics, oral anticoagulants and antiplatelets and
      drugs with a narrow therapeutic index. Warfarin, digoxin and insulin accounted
      for a quarter of the AEs. CONCLUSIONS: Some commonly used medications account for
      a major proportion of AEs in elderly. Prospective studies of similar nature could
      further help us assess the burden of AEs in elderly.

PMID- 19584487
TI  - The effect of clofibrate with phototherapy in late pre-term newborns with non
      hemolytic jaundice.
AB  - BACKGROUND: Despite an understanding of the enzymatic pathways leading to
      bilirubin production and degradation, very few pharmacologic interventions are
      utilized and the mainstay of treatment remains phototherapy. AIMS: To evaluate
      the efficacy of clofibrate in reducing total serum bilirubin levels in late pre
      term neonates with non-hemolytic jaundice. DESIGN AND SETTING: Double-blind,
      placebo-controlled, randomized trial; tertiary level neonatal unit. MATERIALS AND
      METHODS: A randomized controlled study was carried out in the neonatal ward of
      Children's Hospital, Tabriz, Iran, over a 1-year period. Sixty-eight healthy late
      pre-term infants readmitted with non-hemolytic hyperbilirubinemia were randomized
      to receive phototherapy and clofibrate (n= 35) or phototherapy and placebo (n=
      33). STATISTICAL ANALYSIS USED: Chi-square test and independent sample 't' test.
      RESULTS: There were no significant differences in the weight, gender, modes of
      delivery and age of neonates between the two groups. Similarly the mean total
      serum bilirubin (TSB) level at the time of admission was not significantly
      different between the two groups [mean+/- SD: 19.72 +/- 1.79 (95% confidence
      interval: 19.12-20.54 mg/dL) vs. 20.05 +/- 2.82 (95% confidence interval, 19.54
      22.04 mg/dL), P= 0.57]. The mean TSB 48 hours after phototherapy [mean+/- SD:
      8.06+/- 1.34 (95% confidence interval: 7.94-10.18 mg/dL) vs.10.94 +/- 2.87 (95%
      confidence interval: 9.92-12.16 mg/dL), P= 0.02] and the mean duration of
      phototherapy [mean+/- SD: 64.32 +/- 12.48 (95% confidence interval: 60-81.6
      hours) vs. 87.84 +/- 29.76 (95% confidence interval: 79.2-108 hours), P< 0.001]
      were significantly lower in the clofibrate-treated group. CONCLUSIONS: Clofibrate
      is an effective adjunctive drug in neonatal hyperbilirubinemia, which results in
      decreased TSB level and reduced duration of phototherapy in late pre-term
      newborns.

PMID- 19584488
TI  - Survival analysis and risk factors for death in tuberculosis patients on directly
      observed treatment-short course.
AB  - BACKGROUND: Tuberculosis is a disease with a high case fatality of 4.65%.
      OBJECTIVES: To describe the survival pattern of patients on Directly Observed
      Treatment-Short course (DOTS) according to categories, age and sex of patients.
      SETTINGS: Tuberculosis unit (TU) at District Tuberculosis Centre (DTC), Yavatmal,
      India. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Data of
      patients registered for DOTS in the year 2004 were collected from the
      tuberculosis register. STATISTICAL ANALYSIS: Kaplan Meier plots and log rank
      tests to assess the survival pattern. Cox proportional hazards model for
      multivariate analysis. RESULTS: A total of 716 patients were registered at the
      TU. The survival rates by the end of the intensive phase were 96%, 93% and 99% in
      categories I, II and III of DOTS, respectively. The cumulative survival rates
      were 93%, 88% and 96% in the three DOTS categories, respectively. There was a
      significant difference in the survival curves amongst the three DOTS categories
      (log rank statistic= 7.26, d.f..= 2, P=0 0.02) and amongst the different age
      groups [log rank statistic= 8.78, d.f.= 3, P= 0.012). There was no difference in
      the survival curves of male and female patients (log rank statistic= 0.05, d.f.=
      1, P= 0.80) and according to type of disease (log rank statistic= 5.63, d.f.= 2,
      P= 0.05). On Cox proportional hazard analysis, age groups of 40 to 60 years
      [adjusted hazard ratio= 7.81 (1.002-60.87)] and above 60 years [adjusted hazard
      ratio= 21.54 (2.57-180.32)] were identified as significant risk factors for
      death. CONCLUSIONS: Age above 40 years is a significant risk factor for death in
      patients of tuberculosis. There was a significant difference in survival curves
      of the three DOTS categories and age groups.

PMID- 19584489
TI  - Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes
      mellitus: a North Indian study.
AB  - BACKGROUND: The vitamin D receptor (VDR) gene is a candidate gene for
      susceptibility to several diseases. Studies on association between VDR
      polymorphisms and risk of type 2 diabetes (T2DM) in different ethnic populations
      are yet inconclusive. AIMS: This study was conducted to evaluate association
      between VDR polymorphisms and genetic susceptibility to T2DM in the north Indian
      population. SETTINGS AND DESIGN: One hundred clinically diagnosed T2DM patients
      and 160 healthy controls from the north Indian population were recruited for
      genetic association study. MATERIALS AND METHODS: Genomic DNA was extracted from
      blood and genotyped for the single nucleotide polymorphism SNPs of FokI (T/C)
      [rs2228570], BsmI (A/G) [rs1544410] and TaqI (C/T) [rs731236] by polymerase chain
      reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.
      STATISTICAL ANALYSIS USED: Genotype distribution and allelic frequencies were
      compared between patients and controls. Mean values and odds ratios (ORs) with
      95% confidence interval (CI) were calculated using SPSS software (version 15.0).
      RESULTS: The genotype distribution, allele and haplotype frequencies of VDR
      polymorphism did not differ significantly between patients and controls. Mean age
      and waist-hip ratio of patients were found to be associated with VDR
      polymorphism. Combination studies showed FFBbtt increased the risk of T2DM in
      north Indians. CONCLUSIONS: Our data suggest that VDR gene polymorphism in
      combination of genotypes is associated with the risk of T2DM and thus requires
      further studies as a probable genetic risk marker for T2DM.

PMID- 19584490
TI  - Salmonella Wien from gastroenteritis cases encountered in Mangalore, India: a
      report of 10 cases and review of the literature.
AB  - Ten cases of gastroenteritis due to S. Wien were reported from a tertiary care
      hospital in Mangalore, in the month of April 2008. Biochemically, it resembles S.
      Paratyphi B or S. Typhimurium. Serotyping was done at the Central Research
      Institute, Kasauli, to confirm the identity. The food source is more likely to be
      chicken or some poultry products. All the 10 cases recovered with symptomatic
      treatment including antimicrobials like fluoroquinolones. To the best of our
      knowledge, no documented report is available from India regarding the prevalence
      of this organism in humans.

PMID- 19584491
TI  - Pancreas divisum and choledochal cyst.
AB  - Pancreas divisum (PD) is the most common congenital variant of the pancreas,
      affecting 5% to 14% of the population. The ventral duct only drains the ventral
      pancreas through the major papilla, whereas the majority of the pancreas drains
      via the dorsal duct through the minor papilla. We report the case of a 21-year
      old woman with recurrent acute pancreatitis who presented with the rare finding
      of choledochal cyst and pancreas divisum (PD). She underwent minor papilla
      sphincterotomy and pancreatic duct stenting. Comparable literature findings of PD
      and choledochal cyst are discussed with regard to the presented case.

PMID- 19584492
TI  - Paraneoplastic erythrocytosis as a primary presentation of hepatocellular
      carcinoma.

PMID- 19584493
TI  - Possible mechanism for zonisamide-induced hyperammonemia in a child with
      citrullinemia type 1.

PMID- 19584494
TI  - Adult-onset Still's disease: a review.
AB  - OBJECTIVE: This article is an attempt to review recent literature regarding
      pathogenesis and clinical and laboratory findings in adult-onset Still's disease
      (AOSD). MATERIALS AND METHODS: A search was conducted in PubMed and Ovid for
      English language publications, using individual or linked search terms "adult
      onset Still's disease," "adult Still's disease," "Still's disease," "AOSD," and
      other related terms, from 1996 to 2009, and the clinically relevant articles were
      subsequently selected. RESULTS: More than 1000 titles were reviewed by the
      authors, and the most important concepts were selected from 143 full-text
      articles. CONCLUSION: Adult-onset Still's disease (AOSD) is a rare systemic
      inflammatory disorder of unknown etiology and pathogenesis, usually presenting
      with high spiking fever accompanied by systemic manifestations. The disease is an
      entity with heterogeneous pathology; and diverse suggested etiologies, clinical
      manifestations and prognoses. There is no single diagnostic test for AOSD;
      rather, the diagnosis is based on a set of criteria, the most important of which
      are indeed clinical, but they also include paraclinical ones. Treatment aims at
      both minimizing inflammation and halting disease progression. For the former,
      nonsteroidal anti-inflammatory drugs have limited efficacy; so glucocorticoids in
      conjunction with disease-modifying antirheumatic drugs are also used. Novel
      therapeutic approaches such as anti-tumor necrosis factor blockade and monoclonal
      antibodies are promising.

PMID- 19584495
TI  - Emergence of novel influenza a H1N1 virus as a pandemic agent.

PMID- 19584496
TI  - Microbes, the moon, and H1N1.

PMID- 19584497
TI  - AIDS-associated parasitic diarrhoea.
AB  - Since the advent of human immunodeficiency virus infection, with its profound and
      progressive effect on the cellular immune system, a group of human opportunistic
      pathogens has come into prominence. Opportunistic parasitic infection can cause
      severe morbidity and mortality. Because many of these infections are treatable,
      an early and accurate diagnosis is important. This can be accomplished by a
      variety of methods such as direct demonstration of parasites and by serological
      tests to detect antigen and/or specific antibodies. However, antibody response
      may be poor in these patients and therefore immunodiagnostic tests have to be
      interpreted with caution. Cryptosporidium parvum, Isospora belli, Cyclospora
      cayetanensis, Microsporidia, Entamoeba histolytica and Strongyloides stercoralis
      are the commonly detected parasites. Detection of these parasites will help in
      proper management of these patients because drugs are available for most of these
      parasitic infections.

PMID- 19584498
TI  - Role of Borna disease virus in neuropsychiatric illnesses: are we inching closer?
AB  - The biological cause of psychiatric illnesses continues to be under intense
      scrutiny. Among the various neurotropic viruses, Borna disease virus (BDV) is
      another virus that preferentially targets the neurons of the limbic system and
      has been shown to be associated with behavioural abnormalities. Presence of
      various BDV markers, including viral RNA, in patients with affective and mood
      disorders have triggered ongoing debate worldwide regarding its aetiopathogenic
      relationship. This article analyses its current state of knowledge and recent
      advances in diagnosis in order to prove or refute the association of BDV in
      causation of human neuropsychiatric disorders. This emerging viral causative
      association of behavioural disorders, which seems to be inching closer, has
      implication not only for a paradigm shift in the treatment and management of
      neuropsychiatric illnesses but also has an important impact on the public health
      systems.

PMID- 19584499
TI  - Probiotics.
AB  - The term "probiotic" was first used in 1965, by Lilly and Stillwell, to describe
      substances secreted by one organism which stimulate the growth of another. The
      use of antibiotics, immunosuppressive therapy and irradiation, amongst other
      means of treatment, may cause alterations in the composition and have an effect
      on the GIT flora. Therefore, the introduction of beneficial bacterial species to
      GI tract may be a very attractive option to re-establish the microbial
      equilibrium and prevent disease. Prebiotic is a non-digestible food ingredient
      that confers benefits on the host by selectively stimulating one bacterium or a
      group of bacteria in the colon with probiotic properties. Both probiotics and
      prebiotics are together called as Synbiotics. Various bacterial genera most
      commonly used in probiotic preparations are Lactobacillus, Bifidobacterium,
      Escherichia, Enterococcus, Bacillus and Streptococcus . Some fungal strains
      belonging to Saccharomyces have also been used. Probiotics have been shown to be
      effective in varied clinical conditions- ranging from infantile diarrhoea,
      necrotizing enterocolitis, antibiotic-associated diarrhoea, relapsing Clostridium
      difficle colitis, Helicobacter pylori infections, inflammatory bowel disease to
      cancer, female uro-genital infection and surgical infections. Lactobacillus
      rhamnosus strain GG has proven beneficial affects on intestinal immunity. It
      increases the number of IgA and other immunoglobulins secreting cells in the
      intestinal mucosa. It also stimulates local release of interferons. It
      facilitates antigen transport to underlying lymphoid cells, which serves to
      increase antigen uptake in Peyer's patches. Probiotics are live microorganisms,
      so it is possible that they may result in infection in the host. The risk and
      morbidity of sepsis due to probiotic bacteria should be weighed against the
      potential for sepsis due to more pathological bacteria and the morbidity of
      diseases for which probiotic bacteria are being used as therapeutic agents. Also,
      future, well-designed placebo controlled studies with validated results are
      required for ascertaining the true health benefits of probiotics The important
      point in this regard is careful selection of the probiotic agent, its dose
      standardization and a thorough knowledge of its beneficial effects.

PMID- 19584500
TI  - Detection of opportunistic DNA viral infections by multiplex PCR among HIV
      infected individuals receiving care at a tertiary care hospital in South India.
AB  - PURPOSE: Opportunistic viral infections cause increased morbidity and mortality
      among human immunodeficiency virus (HIV) infected individuals, especially those
      who are not on antiretroviral treatment. Early diagnosis of these opportunistic
      viruses will be able to reduce the risk of disease progression with appropriate
      intervention. MATERIALS AND METHODS: Multiplex PCR was attempted to detect the
      opportunistic herpes viruses (HSV-1, HSV-2, VZV, EBV, and CMV), adenovirus and
      polyoma viruses (JC and BK) in three cocktails of PCR reactions. Subsequently,
      all the viruses detected were quantitated by testing using monoplex real time
      PCR. Whole blood samples collected between 2006 and 2007 from 68 treatment naive
      HIV-1 infected and 30 normal healthy individuals were tested for these eight
      viruses. Among the 68 HIV-1 infected individuals 35 had CD4+ T cell count less
      than or equal to 200 while the other 33 had greater than 200 CD4+ T cells.
      RESULTS: Among the 68 HIV-1 infected individuals, 49 (72%) were positive for EBV,
      5 (7%) samples were positive for CMV. All the five CMV positive individuals had
      CD4+ T cell count of less than or equal to 200 cells/microL. The mean EBV load
      among the individuals with a CD4+ T cells of less than or equal to 200
      cells/microL was 3.88 log(10) while among those with greater than 200 CD4+ T
      cells it was 3.75 log(10) . The mean CMV load was 6.98 log(10). Three samples
      were positive for both CMV & EBV. None of the samples was positive for HSV-1, HSV
      2, VZV, Adenovirus, JC and BK viruses. CONCLUSIONS: In our study, multiplex PCR
      based detection system was found useful in detecting opportunistic viruses in HIV
      infected individuals. Though EBV is the most prevalent opportunistic viral
      infection among HIV infected individuals, there was no significant association
      between EBV load, CD4+ T cell counts and HIV-1 virus load. CMV was seen in HIV
      infected individuals with low CD4+ T cell counts (less than 200 cells/microL).

PMID- 19584501
TI  - Evaluation of the bactec MGIT 960 TB system for recovery and identification of
      Mycobacterium tuberculosis complex in a high through put tertiary care centre.
AB  - AIM: To evaluate the performance of an automated BACTEC MGIT 960, a non
      radioactive, non-invasive liquid culture system for cultivation of M.
      tuberculosis complex in terms of recovery rate and time. MATERIALS AND METHODS:
      From March 2005 to December 2007, 14,597 specimens were processed using the MGIT
      960 system and the results were compared with conventional L.J medium. We
      standardised r-nitro benzoic acid (PNBA) assay on MGIT 960 TB system for
      identification of M. tuberculosis complex and evaluated its usefulness by
      comparing the results with an in-house molecular assay and sequencing. RESULTS
      AND DISCUSSION: Of the total 6143 (42%) isolates positive for M. tuberculosis
      complex, 6015 (41%) were positive by MGIT 960 TB system. In contrast, 3526 (24%)
      M. tuberculosis complex isolates grew on the conventional L.J medium. The mean
      turn around time for mycobacterial growth in smear-positive specimens was nine
      days for MGIT 960, and 38 days for L.J. medium whereas in smear negative
      specimens it was 16 days by MGIT vs. 48 days by L.J. CONCLUSION: MGIT 960 system
      with PNBA assay for identification of M. tuberculosis complex is a rapid and
      useful method in laboratories processing a large number of specimens.

PMID- 19584502
TI  - Congenital CMV infection; diagnosis in symptomatic infants.
AB  - BACKGROUND: Samples from babies exhibiting clinical symptoms suggestive of
      congenital infection are referred regularly to NICD, New Delhi,, from Government
      Hospitals located in Delhi and a home for abandoned children (Palna), for the
      diagnosis of etiological agents like toxoplasma, rubella, CMV and herpes. Blood
      samples of mothers of most of the affected babies are also received. OBJECTIVE:
      Evaluation of rapid and accurate technique for the diagnosis of congenital CMV
      infection. MATERIALS AND METHODS: One hundred and twenty five blood samples
      suggestive of symptomatic congenital CMV infection were selected from samples
      received at NICD during the period June 2005-March 2007. A request to collect and
      send the urine samples of the selected babies was sent to the respective
      hospitals. Serum samples of the babies were tested for CMV-IgM antibodies using
      micro-capture ELISA. Mothers' serum samples were subjected to CMV-IgM and IgG
      class antibodies assay by commercial ELISA kits. DNA isolation and amplification
      was performed in urine samples and some of the serum samples using a commercial
      PCR kit for detection of HCMV. Blood and urine samples from 20 normal babies were
      included in the study. RESULTS: Twenty Seven serum samples (21.6%) of infants, of
      the 125 tested, were positive for CMV-IgM antibodies. Twenty five samples (20%)
      showed amplification of CMV-DNA. All 25 samples positive for PCR were positive
      for CMV IgM antibodies. Sera of 73 mothers, out of 75 tested (97.3%), were
      positive for CMV IgG antibodies. However, none of them was positive for CMV IgM
      antibodies. Mothers of all 27 positive babies were positive for CMV-IgG
      antibodies. Serum and urine samples from 20 normal babies were negative for ELISA
      and PCR. CONCLUSION: micro-capture ELISA technique was found to be more sensitive
      than PCR (92.6%) for detection of congenital CMV infection. ELISA is also rapid,
      less cumbersome and cost effective for diagnosis of CMV infection.

PMID- 19584503
TI  - Characterization of RPO B gene for detection of rifampicin drug resistance by
      SSCP and sequence analysis.
AB  - PURPOSE: Because of the emergence of multidrug-resistant tuberculosis in recent
      times, the rapid detection of resistance to the first-line anti-tuberculosis drug
      rifampicin was felt worldwide. Accordingly, this study was conducted to evaluate
      the diagnostic potential of polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) for checking its utility as a rapid screening test for
      determination of rifampicin drug resistance. MATERIALS AND METHODS: A total of 34
      isolates of Mycobacterium tuberculosis (M. tuberculosis) (22 rifampicin
      resistant, 11 rifampicin sensitive and one control H37Rv) strains were analysed
      by PCR-SSCP and DNA sequencing within the 157-bp region of the rpo B gene (Ala
      500-Val 550). RESULTS: Rifampicin resistance was detected successfully by PCR
      SSCP in 20/22(90.90%) of rifampicin-resistant strains showing a total of nine
      different mutations in seven codon positions: codon 513 (CAA-->CCA), 516 (GAC-
      >GTC), 507 (GGC-->GAC), 526 (CAC-->GAC, TAC), 531 (TCG-->TTG, TGG), 522 (TCG-
      >TGG) and 533 (GTG-->CCG). Two rifampicin-resistant strains showed an identical
      PCR-SSCP pattern with the wild type H37Rv; 77.27% rifampicin-resistant strains
      showed a single point mutation and 9.09% had no mutation. Three rifampicin
      resistant strains showed characteristic double mutations at codon positions 526
      and 531. Sensitivity and specificity were calculated as 90.90% and 100%.
      CONCLUSIONS: Rifampicin-resistant genotypes were mainly found in codon positions
      516, 526 and 531. PCR-SSCP seems to be an efficacious method of predicting
      rifampicin resistance and substantially reduces the time required for
      susceptibility testing from 4 to 6 weeks to a few weeks.

PMID- 19584505
TI  - Efficacy of nasopharyngeal culture in identification of pathogen in middle ear
      fluid in chronic otitis media with effusion.
AB  - PURPOSE: Chronic otitis media with effusion (OME) is the leading cause of hearing
      loss during childhood. In bacterial etiology of OME, the most frequent pathogens
      responsible are Haemophilus influenzae followed by Streptococcus pneumoniae and
      Moraxella catarrhalis. This study aimed at evaluating the accuracy of
      nasopharyngeal (NP) specimens in the identification of pathogens in the middle
      ear fluid (MEF) in patients with OME. MATERIALS AND METHODS: In this cross
      sectional, case-control study, 95 MEFs and 53 NP secretion specimens were
      obtained from 53 children. As a control group, 102 NP specimens were taken from
      children having an operation other than an otological disease. Conventional
      culture methods and multiplex-PCR method have been used to determine the etiology
      of OME; NP carriage between cases and control groups were compared using
      conventional culture methods. Pearson Chi-Square and Fisher's Exact tests were
      used in statistical analysis. RESULTS: Bacteria were isolated by culture in 37.9%
      of MEF specimens, 14.7% of which belonged to the group H. influenzae, S.
      pneumoniae and M. catarrhalis. PCR was positive in 30.5% specimens targeting the
      same pathogens. There was a two-fold increase in carriage rate of S. pneumoniae
      and H. influenzae in patients than controls for each pathogen. CONCLUSION: PCR is
      a more reliable method to detect middle ear pathogens in MEF in comparison with
      the conventional culture methods. The NP colonization wasn't found to be an
      indicator of the pathogen in MEF although middle ear pathogens colonize more in
      nasopharynx of diseased children.

PMID- 19584504
TI  - Drug resistant mutations detected by genotypic drug resistance testing in
      patients failing therapy in clade C HIV-1 infected individuals from India.
AB  - PURPOSE: There has been an increase in the number of individuals administered
      antiretroviral therapy (ART) in India but treatment outcome is hampered by
      increasing development of drug resistance. Previous reports from India have shown
      M184V as the commonest mutation in treated individuals. However, there is no
      evidence for any protease mutations in these reports. This study was done to
      observe the common/unique mutational patterns observed in reverse transcriptase
      (RT) and protease (Pr) genes of clade C HIV-1 strains from individuals showing
      treatment failure in India. MATERIALS AND METHODS: The assay was done by
      sequencing the Pr and RT genes of the HIV-1 strains from 18 individuals failing
      ART. Analysis was carried out using Stanford HIV drug resistance database (SHDB).
      The sequences were also submitted to the calibrated population resistance tool of
      SHDB and Rega HIV-1 sub typing tool. Phylogenetic analysis and quality control
      were performed with Mega 4. RESULTS: Among the 20 strains, 19 showed resistance
      to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside
      reverse transcriptase inhibitors (NNRTIs), one strain to NNRTIs and five strains
      showed protease inhibitors (PI) resistance and 3-class resistance. The most
      common mutation conferring NRTI resistance was M184V (90%) while K103N (45%) was
      the most common mutation conferring NNRTI resistance. The M46I mutation was seen
      in 20% of the Pr sequences. CONCLUSION: Resistance testing to check the
      prevalence of drug resistance mutations that arise following failure of the first
      line regimen to establish guidelines for second line regimens in India is a must.
      Studies are needed to confirm if mutation patterns that arise among clade C
      following failure of ART are the same as for clade B strains.

PMID- 19584506
TI  - Dermatophytes, related keratinophilic and opportunistic fungi in indoor dust of
      houses and hospitals.
AB  - Dermatophytes, related keratinophilic and opportunistic fungi were isolated from
      indoor dust samples of 46 hospitals and 47 houses in Kanpur. A total of 19 fungi
      represented by 11 genera were isolated by the hair-baiting technique from 230 and
      235 samples from hospitals and houses respectively. The isolated fungi are
      Acremonium implicatum (Indian Type Culture Collection) ITCC 5266, A. strictum
      (Germplasm Centre for Keratinophilic Fungi) GPCK 1137, Aphanoascus fulvescens
      GPCK 1081, Arthroderma simii GPCK 1275, Chrysosporium queenslandicum ITCC 5270,
      C. indicum ITCC 5269, C. pannicola GPCK 1022, C. tropicum GPCK 1269, Ctenomyces
      serratus ITCC 5267, Gymnoascus reessii ITCC 5265, Malbranchea fulva GPCK 1075,
      Malbranchea pulchella ITCC 5268, Micosporum gypseum GPCK 1038 , Microsporum
      cookei GPCK 2001, M. fulvum GPCK 2002, Paecilomyces lilacinum GPCK 1080,
      Penicillium expansum GPCK 1082, Trichophyton mentagrophytes GPCK 2003 and T.
      terrestre GPCK 2004. In hospitals, the minimum frequency was of Ctenomyces
      serratus ITCC 5267 while the maximum frequency was of Arthroderma simii GPCK
      1275. In houses, Chrysosporium queenslandicum ITCC 5270 and C. tropicum GPCK 1269
      were with minimum and maximum frequencies respectively. This makes the first
      report of these fungi with keratinolytic ability in the indoor dust of hospitals
      and houses.

PMID- 19584507
TI  - Isolation and identification of nontuberculous mycobacteria from water and soil
      in central India.
AB  - Nontuberculous mycobacteria (NTM), important organisms in the Genus Mycobacterium
      and commonly present in the environment, are known to cause disseminated disease
      in AIDS patients. In this study, NTM were isolated from environment (soil and
      water) of the AIDS patients with disseminated NTM disease to know the prevalence
      of environmental NTM species and their correlation with clinical isolates from
      patients of the same area. Paraffin baiting technique was used to isolate NTM
      from environmental samples. Once isolated, subcultures were made on Lowenstein
      Jensen and Middlebrook 7H10 media and the species were identified using
      phenotypic and genotypic techniques. A total of 26 NTM isolates belonging to
      seven different species could be identified. Mycobacterium avium was the only
      species isolated from both clinical and environmental samples of the same
      patient; but the isolates did not match using PCR for IS 1311 and IS 1245 spacer
      sequences.

PMID- 19584508
TI  - Microbicides in India-present and future.
AB  - India continues to wage a battle against the human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome (AIDS) epidemic. Despite an array of
      preventive and control efforts directed against the disease, it continues to
      finds its way from the high risk groups to the general population. Women are more
      vulnerable to HIV/AIDS because of biological as well as socio-cultural factors.
      Microbicides appear to provide an attractive option as a means of protection to
      be used by women. At present, microbicide trials are in study phases I and II in
      India. The development of an ideal microbicide candidate which would be effective
      and confirms to user satisfaction poses a major challenge to researchers.

PMID- 19584510
TI  - Food poisoning due to Salmonella enterica serotype weltevreden in Mangalore.
AB  - An outbreak of food poisoning due to Salmonella enterica serotype Weltevreden (
      S.weltevreden ) involving 34 students has been reported from a tertiary care
      hospital in Mangalore. The symptoms developed 8-10 hours, after consuming a non-
      vegetarian dish, probably fish, from an outside caterer. The identity of the
      organism was confirmed at Central Research Institute, Kasauli. This report
      emphasizes the geographical distribution of this organism in the Coastal
      Karnataka region. S.Weltevreden may be overlooked due to the biochemical
      similarity to S. Paratyphi B & S. Typhimurium.

PMID- 19584509
TI  - Evaluation of a rapid immunochromatographic device for the detection of IgM & IgG
      antibodies to dengue viruses (DENV) in a tertiary care hospital in south India.
AB  - This study has evaluated the performance of a rapid immunochromatographic test
      (ICT) device in detecting antibodies to Dengue virus (DENV) in a tertiary
      hospital in South India. Sera from hospital attendees, with requests for DENV
      antibody testing, were tested with the Panbio Dengue Duo Cassette and a reference
      antibody capture assay for the detection of IgM (Dengue IgM capture ELISA
      National Institute of Virology, India) and IgG (Dengue IgG capture ELISA-Panbio
      Diagnostics Inc., Australia) antibodies. The ICT results were compared with
      results of antibody capture tests for the detection of the IgM and IgG
      antibodies, respectively. Accuracy indices for IgM and IgG detection,
      respectively were -- sensitivity 81.8% and 87.5%, specificity 75.0%, and 66.6%,
      positive predictive value (PPV) 61.0% and 72.9% and negative predictive value
      (NPV) 89.6% and 83.9%. The device performs poorly in detection of IgM and IgG
      antibodies to DENVs and is not recommended for use as a stand-alone diagnostic
      test.

PMID- 19584511
TI  - Isolated pancreatic tuberculosis.
AB  - Isolated pancreatic tuberculosis (TB) is extremely rare, even in countries where
      TB is endemic. The recent increased reporting of TB of the pancreas is related to
      a worldwide increase in TB and an increase in emigration from countries where TB
      is endemic into countries where more sophisticated healthcare and diagnostic
      facilities are available. Herein, we report an unusual case of isolated
      pancreatic region TB, which presented with dyspeptic symptoms and was diagnosed
      by ultrasonography-guided needle aspiration and computed tomography scan of the
      abdomen. This case is unique with regard to abundant bacterial load, as evident
      by Ziehl Neelsen staining and absence of evidence of TB elsewhere. Pancreatic TB
      should be considered as a differential diagnosis of a pancreatic mass and most
      patients have an excellent clinical response to standard antituberculosis
      regimens.

PMID- 19584512
TI  - Neonatal melioidosis: a case report from India.
AB  - Melioidosis, caused by Burkholderia pseudomallei , is an infectious disease of
      major public health importance in Southeast Asia and Australia. We report, for
      the first time from the Indian subcontinent, a case of melioidosis in a neonate,
      its clinical presentation, microbiological diagnosis, possible mode of
      transmission and outcome. A pre-term female baby developed respiratory distress
      soon after birth. The child was febrile, had tachypnea, grunting, normal heart
      rate with a low pulse volume and poor peripheral perfusion. Chest X-ray revealed
      right-sided bronchopneumonia. B. pseudomallei was isolated from the blood culture
      of the neonate collected aseptically. The neonate was successfully treated with
      meropenem.

PMID- 19584513
TI  - Mycobacterium thermoresistibile: case report of a rarely isolated mycobacterium
      from Europe and review of literature.
AB  - Mycobacterium thermoresistibile is a non-tuberculous mycobacterium strongly
      associated with human infections. Since 1966, there have only been six reports of
      its isolation from clinical samples. We report on the first case from Europe and
      review all the previous cases. Identification was achieved with sequencing of the
      16S rRNA and hsp65 genes. This study presents its phenotypic and biochemical
      profile, susceptibilities to selected antibiotics and hsp65 polymerase chain
      reaction-restriction fragment length polymorphism profile with BsteII and Hae III
      .

PMID- 19584514
TI  - Hantavirus infection: a case report from India.
AB  - The clinical presentation of hantavirus infections in India is unclear. We report
      here a case of hantavirus infection in a 46 year old quarry worker presenting
      with fever, abdominal pain, jaundice, thrombocytopenia and renal dysfunction.
      Seroconversion and rising anti-hantavirus IgG titers were taken as evidence of
      hantavirus infection. Clinicians should consider hantavirus infections in the
      differential diagnosis of acute febrile illness along with scrub typhus,
      leptospirosis and dengue.

PMID- 19584515
TI  - Uncommon presentation of pulmonary aspergilloma.
AB  - Cases of pulmonary aspergilloma without any predisposing factors are rarely
      reported. Clinical presentation varies from case to case. Here, we report a case
      of pulmonary aspergilloma in a 60-year-old male patient who was admitted to the
      Intensive Respiratory Care Unit with spontaneous pneumothorax. The patient had a
      history of dyspnea on exertion since 9 months and mild haemoptysis since the last
      6 months. A computerised tomographic scan of the lungs showed a lesion in the
      left main bronchus along with obstructive emphysema of the right lung, moderate
      pneumothorax and mediastinal emphysema. Bronchoscopy was performed and the biopsy
      samples were processed for histopathological examination and culture on
      Sabouraud's dextrose agar, which yielded growth of Aspergillus flavus. Repeat
      sputum samples also yielded the growth of A. flavus. The patient responded to
      intravenous liposomaamphotericin B and intercostal drainage.

PMID- 19584516
TI  - Familial tularaemia.
AB  - Tularaemia is a zoonotic disease caused by Francisella tularensis . In this
      report, we have presented an early stage case of tularemia with fever and
      pharyngitis and two cases from the same non-endemic region with typical
      lymphadenitis. All three patients were treated with non-specific medications in
      healthcare centres, the treatment being directed towards symptoms resembling
      those of upper respiratory tract infections. However, there was no regression in
      their complaints. Because the first case had been treated earlier, his
      lymphadenopaties regressed and there was no suppuration. The other two cases,
      which had been suspected to be exposed to the same pathogen based on their
      histories, were at a mild acute phase and presented to our clinic with typical
      lymphadenitis. The diagnoses of each of the three patients were made
      serologically. An early clinical recovery was achieved in the first patient with
      streptomycin (1 x 1 g/day im) and doxycyline (2 x 100 mg/day peroral) therapy.
      The therapy was prolonged to 4 weeks in the other two cases according to lymph
      node response and no complications occurring in their follow-ups. It can be
      concluded that tularaemia should be considered in the differential diagnosis of
      patients with fever, pharyngitis, conjunctivitis and cervical lymphadenopathies
      that do not respond to beta-lactam antibiotics.

PMID- 19584517
TI  - PPTCT of HIV: two and a half year experience at MKCG medical college, Berhampur,
      India.

PMID- 19584518
TI  - Ciprofloxacin breakpoints in enteric fever: time to revise our susceptibility
      criteria.

PMID- 19584519
TI  - Comparison of performance characteristics of automated PCR systems with culture
      for detection of MTB complex from clinical samples in central India.

PMID- 19584520
TI  - Bacterial contamination of mobile phones of health care workers.

PMID- 19584521
TI  - Etiology and risk factors for early onset neonatal sepsis.

PMID- 19584522
TI  - Root-determined hypernodulation mutant of Lotus japonicus shows high-yielding
      characteristics.
AB  - Here we report the phenotypic characteristics of a novel hypernodulation mutant,
      Ljrdh1 (root-determined hypernodulation 1) of Lotus japonicus. At 12 weeks after
      rhizobial inoculation, there were no differences between the growth of Ljrdh1
      and, wild-type. However, Ljrdh1 showed 2 to 3 times higher nitrogen-fixing
      activity, and seed and pod yields, were approximately 50% higher than the wild
      type. This is the first report of a legume hypernodulation mutant showing normal
      growth and a high-yielding characteristic under optimal cultivation conditions.

PMID- 19584523
TI  - Delphinidin ameliorates beta-amyloid-induced neurotoxicity by inhibiting calcium
      influx and tau hyperphosphorylation.
AB  - Beta-amyloid (Abeta) has been suggested to induce neurotoxicity in Alzheimer's
      disease. We evaluated the neuroprotective effects of delphinidin, an
      anthocyanidin commonly present in pigmented fruits and vegetables, against Abeta
      induced toxicity. Abeta (25-35) significantly decreased the viability of PC12
      cells, and this was accompanied by an increase in intracellular calcium levels
      and tau phosphorylation. However, treatment with delphinidin rescued PC12 cells
      from Abeta by attenuating the elevation of intracellular calcium levels and tau
      phosphorylation. Taken together, these results suggest that delphinidin protects
      PC12 cells against Abeta-induced toxicity by attenuating intracellular calcium
      influx and tau hyperphosphorylation.

PMID- 19584524
TI  - Further evaluation of the localization and functionality of hemagglutinin epitope
      and fluorescent protein-tagged AtMinD1 in Arabidopsis thaliana.
AB  - Symmetric chloroplast division requires a prokaryote-derived division regulator
      protein MinD, whose subchloroplastic localization remains to be completely
      established. We investigated the localization and functionality of AtMinD1
      (Arabidopsis thaliana MinD) fused with a dual hemagglutinin epitope (dHA) or a
      yellow fluorescent protein (YFP). AtMinD1-dHA, which successfully complemented
      the arc11/atminD1 mutant phenotype, was predominantly located at the envelope
      membrane and the mid-chloroplast constriction site. Meanwhile, AtMinD1-YFP was
      non-functional and showed suborganellar localization partly similar to that of
      AtMinD1-dHA. This prompts us to reevaluate earlier transgenic and transient
      expression studies using fluorescent protein-tagged AtMinD1.

PMID- 19584525
TI  - Purification and characterization of a (R)-1-phenyl-1,3-propanediol-producing
      enzyme from Trichosporon fermentans AJ-5152 and enzymatic (R)-1-phenyl-1,3
      propanediol production.
AB  - An (R)-1-phenyl-1,3-propanediol-producing enzyme was purified from Trichosporon
      fermentans AJ-5152. It was NADPH-dependent and converted 3-hydroxy-1
      phenylpropane-1-one (HPPO) to (R)-1-phenyl-1,3-propanediol [(R)-PPD] with anti
      Prelog's specificity. It showed maximum activity at pH 7.0 and 40 degrees C. Its
      K(m) and V(max) values toward HPPO were 20.1 mM and 3.4 mumol min(-1) mg protein(
      1) respectively. The relative molecular weight of the enzyme was estimated to be
      68,000 on gel filtration and 32,000 on SDS-polyacrylamide gel electrophoresis. An
      (R)-PPD-producing reaction using the (R)-PPD-producing enzyme and an NADPH
      recycling system was carried out by successive feeding of HPPO. A total (R)-PPD
      yield of 8.9 g/l was produced in 16 h. The molar yield was 76%, and the optical
      purity of the (R)-PPD produced was over 99% e.e.

PMID- 19584526
TI  - Isolation of Pseudomonas sp. strain HB01 which degrades the persistent brominated
      flame retardant gamma-hexabromocyclododecane.
AB  - In this study, we isolated Pseudomonas sp. strain HB01 from a soil sample
      contaminated with brominated pollutants, and found that it degraded gamma
      hexabromocyclododecane (gamma-HBCD). The strain degraded 81% of 1 mM gamma-HBCD
      within 5 d of culture. Furthermore, it demonstrated biodegradation of
      structurally related (bromo) alkanes. To the best of our knowledge, this is the
      first report that outlines the isolation of a bacterial strain that degrades
      gamma-HBCD.

PMID- 19584528
TI  - Use of whole crop sorghums as a raw material in consolidated bioprocessing
      bioethanol production using Flammulina velutipes.
AB  - The possibility of using two kinds of sorghum as raw materials in consolidated
      bioprocessing bioethanol production using Flammulina velutipes was investigated.
      Enzymatic saccharification of sweet sorghum was not as high as in brown mid-rib
      (bmr) mutated sorghum, but the amount of ethanol production was higher. Ethanol
      production from bmr mutated sorghum significantly increased when saccharification
      enzymes were added to the culture.

PMID- 19584527
TI  - Analysis of gene transcripts in a crude oil-degrading marine microbial community.
AB  - We established a procedure for analyzing gene transcripts in a microbial
      community of unknown genomic background. Analysis of a crude oil-degrading marine
      microbial community detected the expression of genes related to the
      biodegradation of fatty acids and the biosynthesis of glycolipids probably
      involved in the emulsification of crude oil.

PMID- 19584529
TI  - The hydrophobicity in a chemically modified side-chain of cysteine residues of
      thanatin is related to antimicrobial activity against Micrococcus luteus.
AB  - The chemically modified thanatins with the methyl group (CH(3)), ethyl group
      (C(2)H(5)), and normal-octyl group (C(8)H(17)) at the side-chain of cysteine
      residues were synthesized. The octyl group modified form exhibited 8-fold higher
      antimicrobial activity against Micrococcus luteus than wild type thanatin. It was
      found that there was an equilateral correlation between antimicrobial activity
      and side-chain hydrophobicity at the cysteine residues in thanatin.

PMID- 19584530
TI  - Pinostrobin from Boesenbergia pandurata is an inhibitor of Ca2+-signal-mediated
      cell-cycle regulation in the yeast Saccharomyces cerevisiae.
AB  - Upon searching plant extracts for inhibitors of the Ca(2+) signaling pathway
      using the zds1Delta-yeast proliferation based assay, a crude rhizome extract of
      Boesenbergia pandurata was found to be strongly positive, and from this extract
      pinostrobin, alpinetin, and pinocembrin chalcone were isolated as active
      components. Further biochemical experiments confirmed that pinostrobin possesses
      inhibitory activity on the Ca(2+) signals involved in the control of G2/M phase
      cell cycle progression in Saccharomyces cerevisiae.

PMID- 19584531
TI  - Antimicrobial activity of elephant garlic oil against Vibrio cholerae in vitro
      and in a food model.
AB  - Vibrio cholera is a major foodborne pathogen in Thailand. It is present in raw
      and lightly cooked foods, and it causes cholera. Natural products inhibiting it
      can be used to improve the safety of foods. In this study, elephant garlic oil
      was studied for its major diallyl sulfide content and its antimicrobial activity
      against V. cholerae. The oil had a very low concentration of diallyl monosulfides
      (1.62%) in comparison with the other diallyl sulfides (25.09% for diallyl
      disulfide, 16.04% for diallyl trisulfide, and 10.58% for diallyl tetrasulfide).
      In an in vitro study, the oil was found to have a bacteriocidal effect on all
      tested strains of V. cholerae, with varied minimal inhibitory concentrations
      (MICs) ranging from 3.13 to 25 microg/ml. It was also found that elephant garlic
      oil retarded the growth of the bacteria or reduced the bacterial cell load in the
      food model, depending on its concentration.

PMID- 19584532
TI  - Properties of a metagenome-derived beta-glucosidase from the contents of rabbit
      cecum.
AB  - In this study, a previously cloned beta-glucosidase gene, umbgl3B, was
      heterologously expressed in Escherichia coli, and the biochemical properties of
      the purified enzyme were characterized. The recombinant enzyme was stable over a
      wide range of pH values (5.0-9.0) and below 30 degrees C. It displayed optimum
      enzymatic activity at pH 6.5 at 40 degrees C, under condition similar to that in
      the rabbit cecum, suggesting an active role of the native enzyme in vivo. The
      recombinant beta-glucosidase Umbgl3B showed high activity to aryl beta-D
      glucosides and low activity to cellooligosaccharides, with a polymerization
      degree of less than 5. The enzyme had no activity toward long
      cellooligosaccharides or polysaccharides. The aspartic acid residue, D772, of the
      wild-type Umbgl3B was predicted as a nucleophile. Mutant D772A was constructed.
      It showed less than 1/10,000 activity of the wild-type enzyme, but had the same
      properties, suggesting that residue D772 plays a key role in the enzyme's
      activity.

PMID- 19584533
TI  - Identification of the electron transfer flavoprotein as an upregulated enzyme in
      the benzoate utilization of Desulfotignum balticum.
AB  - Desulfotignum balticum utilizes benzoate coupled to sulfate reduction. Two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) analysis was conducted
      to detect proteins that increased more after growth on benzoate than on butyrate.
      A comparison of proteins on 2D gels showed that at least six proteins were
      expressed. The N-terminal sequences of three proteins exhibited significant
      identities with the alpha and beta subunits of electron transfer flavoprotein
      (ETF) from anaerobic aromatic-degraders. By sequence analysis of the fosmid clone
      insert (37,590 bp) containing the genes encoding the ETF subunits, we identified
      three genes, whose deduced amino acid sequences showed 58%, 74%, and 62% identity
      with those of Gmet_2267 (Fe-S oxidoreductase), Gmet_2266 (ETF beta subunit), and
      Gmet_2265 (ETF alpha subunit) respectively, which exist within the 300-kb genomic
      island of aromatic-degradation genes from Geobacter metallireducens GS-15. The
      genes encoding ETF subunits found in this study were upregulated in benzoate
      utilization.

PMID- 19584534
TI  - Characteristics of novel insect defensin-based membrane-disrupting trypanocidal
      peptides.
AB  - Synthetic D- and L-amino acid type cationic 9-mer peptides (all sequences were
      synthesized as D- or L-amino acids) derived from the active sites of insect
      defensins were tested for their ability to modify the growth of blood-stream form
      African trypanosomes in vitro. One of them, the D-type peptide A (RLYLRIGRR
      NH(2)), irreversibly suppressed proliferation of the Trypanosoma brucei brucei
      GUTat3.1 parasite. The presence of negatively charged phosphatidylserine on the
      surface of the parasites was demonstrated, suggesting electrostatic interaction
      between the peptide and the phospholipids. Furthermore, this peptide was found to
      alter trypanosome membrane-potentials significantly, an effect apparently due to
      the removal of the parasite's plasma membrane. The potential toxic effects of D
      peptide A on mammalian cells was assessed using human brain microvascular
      endothelial cells. Only minor effects were found when the endothelial cells were
      exposed for 16 h to peptide concentrations of less than 200 microM. These
      findings suggest that insect defensin-based peptides represent a potentially new
      class of membrane-disrupting trypanocidal drugs.

PMID- 19584535
TI  - Syntheses and antimicrobial activity of tetrasubstituted tetrahydrofuran lignan
      stereoisomers.
AB  - The syntheses of all stereoisomers of tetrasubstituted tetrahydrofuran lignan
      were accomplished, and the antimicrobial activity was examined. The 9,9'-diol
      compound bearing (7R,7'R,8R,8'R) and (7R,7'S,8R,8'R) stereochemistry showed the
      strongest antibacterial activity against Listeria denitrificans and Bacillus
      subtilis, respectively. It was also found that (-)-virgatusin bearing
      (7S,7'R,8S,8'S) stereochemistry had strongest antifungal activity.

PMID- 19584537
TI  - Functional analyses of immediate early gene ETR101 expressed in yeast.
AB  - ETR101, a human homolog of rat pip92, is a cellular immediate early gene induced
      by extracellular stimuli such as serum growth factors. ETR101 encodes a short
      lived, proline-rich protein (ETR101) exhibiting no significant sequence
      similarity to any other known protein, and little is known about its function. We
      investigated the functioning of ETR101 as a transcriptional activator for the
      gene ISYNA1, which encodes human inositol 1-phosphate synthase. We constructed a
      yeast strain in which the chromosomal region of the PSS1 promoter was replaced
      with the human ISYNA1 promoter. Using this yeast strain, we screened human cDNAs,
      which activated the ISYNA1 promoter, and thus expressed the PSS1 as a reporter
      gene. We obtained two types of cDNA, E2F1, known as a gene encoding Rb-binding
      protein, and ETR101. The E2F1 gene product (E2F1) is known to bind to and
      activate the ISYNA1 promoter. In a manner similar to E2F1, ETR101 binds to and
      activates the ISYNA1 promoter.

PMID- 19584536
TI  - Isolation of single chain variable fragments against six esters of pyrethrins by
      subtractive phage display.
AB  - Recombinant antibodies (rAbs) are a new diagnostic test for immulogical
      detection. To date, there are no reports about anti-pyrethrins rAbs. Here we
      describe the generation of monomeric and dimeric single chain variable fragments
      (scFvs) with affinity for six esters of pyrethrins using a subtractive phage
      display technology. First, scFv libraries with long-linker (Ger(4)Ser)(3) and
      short-linker (Ger(4)Ser) were established to contain 1.04 x 10(7) or 6.07 x 10(6)
      transformants. After four rounds of panning, phage ELISA demonstrated that three
      clones (E2, F2, and H7) showed higher affinity from the long-linker library, and
      clones (h6, a5) exhibited better antibody activity to pyrethrin I and II from the
      short-linker library. The scFv candidates were sequenced to identify the specific
      antibody response against pyrethrins. Isolated scFvs constitute valuable tools
      for real-time detection of pyrethrins. In addition, the subtractive phage display
      provides a simple approach for isolation of scFvs.

PMID- 19584538
TI  - Molecular cloning and expression of starfish protein kinase C isoforms.
AB  - To investigate the roles of protein kinase C (PKC) isoforms in Echinoderms, we
      cloned starfish cDNAs for novel, atypical, and conventional PKCs. They showed
      highest homology with PKCdelta, iota, and alpha isoforms respectively. It was
      predicted from the whole genome sequence and by RT-PCR that sea urchin has only
      one isoform of each PKC subgroups. It is thus likely that these isoforms are the
      prototypes or ancestors of the PKC subgroups. The phylogenetic tree suggests that
      atypical PKC was first formed by evolution from the common prototype of AGC
      protein kinase family, and novel and conventional PKCs next. RT-PCR analysis
      indicated that novel and atypical PKC mRNAs are expressed ubiquitously in all
      tissues of adult starfish, whereas conventional PKC mRNA is expressed mainly in
      the ovary and oocytes, and only slightly in the tube foot and stomach. Upon
      heterologous expression, only atypical PKC was expressed in the functional form
      in insect cells.

PMID- 19584539
TI  - Molecular heterogeneity of TIME-EA4, a timer protein in silkworm diapause eggs.
AB  - TIME-EA4 is an ATPase that measures time intervals as a diapause-duration clock
      found in diapause eggs of the silkworm, Bombyx mori. In the current studies, we
      report the molecular heterogeneity of TIME-EA4 protein regarding not only amino
      acid L62V, but also the numbers and linkage patterns of the sugar chain attached
      to the Asn(22) residue. These sugar chain structures were determined in a pico
      molar amount of the protein by combining the methods of chemical modification
      (Smith degradation) and nano-HPLC-electrospray ionization-quadrupole-time of
      fight-mass spectrometry (ESI-Q-TOF-MS) and -MS/MS. The Japanese and bi-voltine
      Thai silkworm strains were compared to show the heterogeneity represented by four
      kinds of molecular species. Judicious choice of the combination methods led us to
      find the first example of a linkage-position difference in the glycosidic bonds
      even in sugar moieties of the same molecular weight; thus, the Man(1-6)Man(1
      4)GlcNAc(1-4)GlcNAc structure in the C108 pure strain and Man(1-3)Man(1
      4)GlcNAc(1-4)GlcNAc structure in the Kinshu-Showa hybrid. A total of five kinds
      of molecular heterogeneity was determined, including the amino acids in TIME-EA4
      protein. This paper describes the details for determining the sugar chain linkage
      in TIME-EA4 from the diapause eggs of various silkworm strains.

PMID- 19584540
TI  - Inhibition of P-glycoprotein enhances the suppressive effect of kaempferol on
      transformation of the aryl hydrocarbon receptor.
AB  - Dioxins enter the body mainly through the diet, bind to the aryl hydrocarbon
      receptor (AhR), and cause various toxicological effects. In this study, we found
      that oral administration of kaempferol or ginkgo biloba extract (EGb) containing
      24% flavonol at 100 mg/kg body weight suppressed AhR transformation induced by 3
      methylcholanthrene at 10 mg/kg body weight in the liver of mice. The suppressive
      effect of kaempferol was enhanced by verapamil, an inhibitor of P-glycoprotein (P
      gp), in ex vivo experiments using a hepatic cytosolic fraction and 2,3,7,8
      tetrachlorodibenzo-p-dioxin. Enhancement of the suppressive effect by verapamil
      was also observed in mouse hepatoma Hepa-1c1c7 cells, accompanied by an increase
      in the uptake of kaempferol into the cells. In conclusion, inhibition of P-gp
      enhanced the suppressive effect of kaempferol on AhR transformation through an
      increase in the intracellular kaempferol concentration.

PMID- 19584541
TI  - Orally administered Lactobacillus paracasei KW3110 induces in vivo IL-12
      production.
AB  - Lactic acid bacteria (LAB) are popularly used as probiotics, and some strains of
      LAB have anti-allergic functions in vivo. Although in vitro studies show that LAB
      modulate the T helper type (Th) 1/Th2 balance and inhibit IgE secretion by
      inducing IL-12, it is not known how LAB regulates allergies in vivo. In this
      study, we evaluated in vivo IL-12 production after oral administration of
      Lactobacillus paracasei KW3110, a strain reported to improve allergies, to mice.
      Orally administered KW3110 interacted with CD11b positive cells and induced IL-12
      mRNA expression at Peyer's patch. In addition, blood IL-12 levels increased
      transiently 10 h after administration of KW3110. Based on these results, we found
      that oral administration of KW3110 induces IL-12 in vivo. Our findings should
      contribute to understanding of the in vivo function of LAB.

PMID- 19584542
TI  - Transgenic lettuce producing a candidate protein for vaccine against edema
      disease.
AB  - Pig edema disease is a bacterial disease caused by Shiga toxin 2e-producing
      Escherichia coli belonging mainly to serotypes O138, O139, and O141. The B
      subunit of Shiga toxin 2e (Stx2eB) is a candidate protein for use in a vaccine
      against edema disease. We produced this protein in transgenic lettuce (Lactuca
      sativa), an edible plant that can be cultivated in a factory setting. In a
      transient expression system, we found that NtADH 5'-untranslated region (5'-UTR)
      functions as a translational enhancer in lettuce cells, and that Stx2eB
      accumulates most efficiently in the endoplasmic reticulum (ER) of lettuce cells.
      Stx2eB was produced in stable transgenic lettuce plants expressing a modified
      Stx2eB gene fused with the NtADH 5'-UTR and sequence encoding ER localization
      signals.

PMID- 19584543
TI  - Characterization of NikA histidine kinase and two response regulators with
      special reference to osmotic adaptation and asexual development in Aspergillus
      nidulans.
AB  - Aspergillus nidulans has many histidine-to-aspartate (His-Asp) phosphorelay
      components, including 15 histidine kinases (HKs), four response regulators (RRs),
      and a histidine-containing phosphotransfer intermediate (HPt). Of these, NikA
      (HK) is highly conserved in many filamentous fungi. It has been found that NikA
      is responsible for the responses of filamentous fungi to fungicides such as
      iprodione and fludioxonil. Two RRs, SskA and SrrA, are also involved in the
      fungicide response, providing a typical example of the His-Asp phosphorelay
      system, in which NikA functions as a sensor upstream of SskA and SrrA in response
      to fungicides. To gain further insight into the physiological roles of the NikA
      SskA/SrrA phosphorelay system, we constructed a pair of DeltanikADeltasskA and
      DeltanikADeltasrrA double mutants. Here we provide evidence regarding the crucial
      involvement of the NikA-SskA/SrrA phosphorelay system in both osmotic adaptation
      and asexual development, including conidia formation. Based on these results, a
      general insight into the A. nidulans His-Asp phosphorelay network is also
      discussed.

PMID- 19584544
TI  - Identification of sam4 as a rad24 allele in Schizosaccharomyces pombe.
AB  - Fission yeast requires nutritional starvation to switch the mitotic cell cycle to
      sexual differentiation, but sam mutants, of which we had isolated nine alleles,
      mate without the starvation condition. These mutants are useful for understanding
      the mechanism underlying the way cells sense nutritional starvation and change
      the cell cycle. To identify the sam allele, we first sought phenotypes other than
      the original sam phenotype. We found that all nine sam mutants were sensitive to
      1 M KCl, that sam2, sam3, sam4 and sam9 were sensitive to 0.1 M CaCl(2), and that
      only the sam4 mutant was sensitive to 150 J/m(2) UV. This peculiar phenotype of
      sam4 suggested to us that sam4 might be an allele of rad24, which encodes a 14-3
      3 protein. In fact, the Rad24 protein disappeared in sam4 and the rad24 mRNA was
      not transcribed in sam4. In addition, the mutation that changed Gln to a stop
      codon was found in the rad24 locus of sam4. Hence we concluded that sam4 is an
      allele of rad24. We also found that over-expression of rad24 or rad25 (a paralog
      of rad24) has a suppressive effect on sam1, and that sam1 was not an allele of
      rad24 nor rad25. Thus 14-3-3 proteins are deeply involved in the switching of the
      mitotic cell cycle to the sexual differentiation of fission yeast.

PMID- 19584545
TI  - Visualization and quantification of three-dimensional distribution of yeast in
      bread dough.
AB  - A three-dimensional (3-D) bio-imaging technique was developed for visualizing and
      quantifying the 3-D distribution of yeast in frozen bread dough samples in
      accordance with the progress of the mixing process of the samples, applying cell
      surface engineering to the surfaces of the yeast cells. The fluorescent yeast was
      recognized as bright spots at the wavelength of 520 nm. Frozen dough samples were
      sliced at intervals of 1 microm by an micro-slicer image processing system
      (MSIPS) equipped with a fluorescence microscope for acquiring cross-sectional
      images of the samples. A set of successive two-dimensional images was
      reconstructed to analyze the 3-D distribution of the yeast. The average shortest
      distance between centroids of enhanced green fluorescent protein (EGFP) yeasts
      was 10.7 microm at the pick-up stage, 9.7 microm at the clean-up stage, 9.0
      microm at the final stage, and 10.2 microm at the over-mixing stage. The results
      indicated that the distribution of the yeast cells was the most uniform in the
      dough of white bread at the final stage, while the heterogeneous distribution at
      the over-mixing stage was possibly due to the destruction of the gluten network
      structure within the samples.

PMID- 19584547
TI  - Electron transfer processes in subunit I mutants of cytochrome bo quinol oxidase
      in Escherichia coli.
AB  - Cytochrome bo is a terminal quinol oxidase in the aerobic respiratory chain of
      Escherichia coli. Subunit I binds all four redox centers, and electrons are
      transferred from quinols to high-spin heme o and Cu(B) through a bound uniquinone
      8 and low-spin heme b. To explore the role of conserved charged amino acid
      residues, we examined the one-electron transfer processes in subunit I mutants.
      We found that all the mutants examined increased the electron transfer rate from
      the bound quinone to heme b more than 40-fold. Tyr288 and Lys362 are key residues
      in the K-channel for charge compensation of the heme o-Cu(B) binuclear center
      with protons. The Tyr288Phe and Lys362Gln mutants showed 100-fold decreases in
      heme b-to-heme o electron transfer, accompanied by large increases in the redox
      potential of heme o. Our results indicate that electromagnetic coupling of hemes
      is important for facilitated heme-heme electron transfer in cytochrome bo.

PMID- 19584546
TI  - Sensitive quantification of bulleyaconitine A in human serum by liquid
      chromatography-tandem mass spectrometry.
AB  - A simple and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      method was developed and validated for the quantification of bulleyaconitine A
      (BLA) in human serum. Samples were extracted from human serum by protein
      precipitation. Domperidone was used as internal standard (I.S.). Chromatography
      separation was performed on a Waters Sunfire C18 column (2.1 x 50 mm, 5 microm)
      with a gradient mobile phase. Detection was performed in positive mode using
      multiple reaction monitoring (MRM) of the transition m/z 644.2>584.3 for BLA and
      m/z 426.3>175.3 for I.S. The proposed method was validated in a linear range of
      0.0587-11.7 ng/ml. Intra- and inter-day precision was better than 9.88% and
      7.76%. The recovery for BLA was 97.90%, and for I.S. 89.40%. This method provides
      a simple, rapid, specific, and sensitive tool for the quantitative determination
      of BLA in human serum, and can be used to monitor serum levels in patients
      treated with BLA.

PMID- 19584548
TI  - Synthesis and field evaluation of methyl-branched ketones, sex pheromone
      components produced by Lithosiinae female moths in the family of Arctiidae.
AB  - Female moths of Lyclene dharma dharma (Arctiidae, Lithosiinae) produce a novel
      sex pheromone composed of three methyl-branched ketones (I-III) in a ratio of
      2:1:1. In order to confirm the structure of III (6,14-dimethyl-2-octadecanone), a
      mixture of its four stereoisomers was synthesized via chain elongation by two
      Wittig reactions, starting from 1,7-hexanediol. GC-MS data of the synthetic III
      were satisfactorily coincident with those of the natural component. In addition
      to the racemic mixtures of I (6-methyl-2-octadecanone) and II (14-methyl-2
      octadecanone), previously synthesized, the activity of III was evaluated in the
      Iriomote Islands, and effective male attraction was observed for the 2:1:1
      mixture of I-III. This result indicates that the females do not produce only one
      stereoisomer for each component or that the response of the males is not
      disturbed by the other stereoisomers of natural isomers produced by the females.
      The field test also revealed that the two-component lure of I and II captured as
      many males as the mixture of I-III, while lures baited with two components in
      other combinations and with only one component scarcely exhibited any male
      attraction ability.

PMID- 19584549
TI  - Identification of high gamma-aminobutyric acid producing marine yeast strains by
      physiological and biochemical characteristics and gene sequence analyses.
AB  - Four marine yeasts isolated from the Pacific Ocean off Japan (Siki No. 4, Siki
      No. 15, Hach No. 6, and Inub No. 11), which showed high gamma-aminobutyric acid
      (GABA) producing abilities, were identified and classified by physiological and
      biochemical characteristics and gene sequence analyses. Analysis of biochemical
      data suggested that while Siki No. 15 was identical to Candida, the remaining
      three isolates belonged to the genus Pichia. However, these data were
      insufficient to resolve their identity at the species level. Subsequently,
      analysis of the 5.8S rRNA genes and the two internal transcribed spacer regions
      (ITS) sequences revealed that Siki No. 15 belongs to Pichia guilliermondii, while
      the remaining three isolates corresponded to Pichia anomala. Since Siki No. 4
      showed slightly different biochemical properties than the other two isolates,
      which were otherwise identical, we sought to investigate the sequences of the
      intergenic spacer region 1 (IGS1). We observed few nucleotide changes, suggesting
      that the Hach No. 6 and Inub No. 11 isolates belong to different but new strains
      for which we propose the names P. anomola MR-1 and MR-2 respectively.

PMID- 19584550
TI  - Application of cell-surface engineering for visualization of yeast in bread
      dough: development of a fluorescent bio-imaging technique in the mixing process
      of dough.
AB  - Cell-surface engineering (Ueda et al., 2000) has been applied to develop a novel
      technique to visualize yeast in bread dough. Enhanced green fluorescent protein
      (EGFP) was bonded to the surface of yeast cells, and 0.5% EGFP yeasts were mixed
      into the dough samples at four different mixing stages. The samples were placed
      on a cryostat at -30 degrees C and sliced at 10 microm. The sliced samples were
      observed at an excitation wavelength of 480 nm and a fluorescent wavelength of
      520 nm. The results indicated that the combination of the EGFP-displayed yeasts,
      rapid freezing, and cryo-sectioning made it possible to visualize 2-D
      distribution of yeast in bread dough to the extent that the EGFP yeasts could be
      clearly distinguished from the auto-fluorescent background of bread dough.

PMID- 19584551
TI  - Construction of a protein library of Arabidopsis transcription factors using a
      wheat cell-free protein production system and its application for DNA binding
      analysis.
AB  - We created a protein library consisting of 647 Arabidopsis transcription factors
      (TFs) using a wheat cell-free system. The quality of proteins in the library was
      checked by binding assay of bZIP family proteins. Screening of TFs binding to 5'
      regulatory regions of FLC and LFY was conducted using the library, and MYB67 and
      GBF1 were found to be binding factors.

PMID- 19584552
TI  - Effects of Lactobacillus fermented soymilk and soy yogurt on hepatic lipid
      accumulation in rats fed a cholesterol-free diet.
AB  - We examined the effects of lactic acid fermented soymilk, in which part of the
      soymilk was replaced with okara (soy yogurt), on plasma and hepatic lipid
      profiles in rats fed a cholesterol-free diet. Additionally, we investigated the
      effects of soy yogurt on hepatic gene expression in rats using DNA microarray
      analysis. Male Sprague-Dawley rats aged 5 weeks (n=5/group) were fed a control
      diet (AIN-93) or a test diet in which 20% of the diet was replaced by soy yogurt
      for 7 weeks. Soy yogurt consumption did not affect body weight or adipose tissue
      weight as compared with control diet. In the soy yogurt group, the liver weight
      and hepatic triglyceride content were significantly lower than the control group,
      and the level of plasma cholesterol was also lower. Furthermore, DNA microarray
      analysis indicated that soy yogurt ingestion down-regulated the expression of the
      SREBP-1 gene and enzymes related to lipogenesis in the rat liver, while
      expression of beta-oxidation-related genes was up-regulated. These results
      suggest that soy yogurt is beneficial in preventing hepatic lipid accumulation in
      rats.

PMID- 19584554
TI  - Isolation and characterization of endophytic Bacillus subtilis Jaas ed1
      antagonist of eggplant Verticillium wilt.
AB  - An endophytic bacterial strain, Jaas ed1, was isolated from the interior of
      eggplant (Solanum melongena L.) stems in Jiangsu Province, China. According to
      the morphological and physiological characteristics and phylogenetic analysis of
      the 16s rDNA sequence, it was identified as Bacillius subtilis. Strain Jaas ed1
      and its cell-free filtrate had strong antifungal activity against Verticillium
      dahliae. The strain was an internal colonizer within the eggplant without any
      harmful side effects to the plant. In greenhouse experiments, the strain cell
      suspension effectively controlled Verticillium wilt of eggplant, and its control
      efficiency was far more significant than that of the cell-free filtrate after
      inoculation of V. dahliae.

PMID- 19584553
TI  - Production of human monoclonal antibodies against Fc(epsilon)RI(alpha) by a
      method combining in vitro immunization with phage display.
AB  - An in vitro immunization protocol using human peripheral blood mononuclear cells
      (PBMC) was developed to generate human antigen-specific antibodies. Monoclonal
      antibodies have great potential, and in particular, efficient acquirement of
      monoclonal antibodies against membrane proteins provides advantages. In this
      study, we tried to generate a human monoclonal antibody against the high affinity
      IgE receptor, Fc(epsilon)RI(alpha), using a method combining in vitro
      immunization and phage display. Heavy and light chain variable region genes were
      obtained from PBMC immunized in vitro with Fc(epsilon)RI(alpha)-expressed KU812F
      cells. Subsequently a combined phage antibody library 6 x 10(3) in the size was
      generated. Antigen-specific phage antibody clones were selected by panning with
      recombinant Fc(epsilon)RI(alpha) and recombined to produce human IgG format
      antibodies using CHO cells. The antibodies exhibited specific binding against
      Fc(epsilon)RI(alpha). These results suggest that one can obtain membrane protein
      specific human monoclonal antibodies from a relatively small phage antibody
      library using in vitro immunized PBMCs.

PMID- 19584555
TI  - The protective immune response against infectious bronchitis virus induced by
      multi-epitope based peptide vaccines.
AB  - Peptide vaccine was found to be an effective and powerful approach to a variety
      of pathogens. To explore multi-epitope based peptide vaccines against infectious
      bronchitis virus (IBV), the immunogenic peptides were fused to the 3' terminal of
      glutathione S transferase gene (GST) and expressed in Escherichia coli. ELISA and
      Western blot analysis showed that the purified fusion proteins had excellent
      immune activity with chicken anti-IBV serum. During the vaccination course, the
      candidate peptide vaccines induced strong humoral and cellular response, and
      provided up to 80.0% immune protection, while all non-immunized chickens in the
      negative control group manifested obvious typical symptoms and died after virus
      challenge. Our finding provides a new way to develop multi-epitope based peptide
      vaccine against IBV.

PMID- 19584556
TI  - Quantitative analysis of saponins in a tea-leaf extract and their
      antihypercholesterolemic activity.
AB  - A novel simple method using liquid chromatography/time-of-flight mass
      spectrometry (LC/TOF-MS) and LC/UV was established for the quantification of
      saponins in an extract from green tea leaves. The amount of saponins in a
      fraction with high in vitro antihypercholesterolemic activity, Fr2-3, was
      determined to be 72%. An in vivo experiment showed that the addition of 0.5% Fr2
      3 to a high-cholesterol diet suppressed the increase in serum cholesterol levels
      in rats. Fr2-3 induced a decrease in the liver cholesterol and triglyceride
      levels and an increase in the fecal excretion of cholesterol. These results
      indicate tea-leaf saponins to be the active components in Fr2-3 and that these
      saponins exhibited antihypercholesterolemic activity by inhibiting cholesterol
      absorption in the intestines.

PMID- 19584557
TI  - Molecular cloning and functional expression of a new amylosucrase from
      Alteromonas macleodii.
AB  - The presence of amylosucrase in 12 Alteromonas and Pseudoalteromonas strains was
      examined. Two Alteromonas species (Alteromonas addita KCTC 12195 and Alteromonas
      macleodii KCTC 2957) possessed genes that had high sequence homology to known
      amylosucrases. Genomic clones containing the ASase analogs were obtained from A.
      addita and A. macleodii, and the deduced amino acid sequences of the
      corresponding genes (aaas and amas, respectively) revealed that they were highly
      similar to the ASases of Neisseria polysaccharea, Deinococcus radiodurans, and
      Deinococcus geothermalis. Functional expression of amas in Escherichia coli was
      successful, and typical ASase activity was detected in purified recombinant AMAS,
      whereas the purified recombinant AAAS was nonfunctional. Although maximum total
      activity of AMAS was observed at 45 degrees C, the ratio of transglycosylation to
      total activity increased as the temperature decreased from 55 to 25 degrees C.
      These results imply that transglycosylation occurs preferentially at lower
      temperatures while hydrolysis is predominant at higher temperatures.

PMID- 19584558
TI  - Production of 3-hydroxypropionaldehyde in silage inoculated with Lactobacillus
      coryniformis plus glycerol.
AB  - We examined the production of an antimicrobial component, 3
      hydroxypropionaldehyde (3-HPA), in laboratory-scale silage inoculated with
      Lactobacillus coryniformis strain 394, which ferments glycerol to 3-HPA. A
      modified colorimetric method that used an NaOH-treated blank and determined the
      absorption spectrum of the samples was employed to detect a 3-HPA-like component
      (HLC) that was assumed to be 3-HPA. Inoculation with Lb. coryniformis 394 plus
      glycerol in ensiling produced HLC at 10-460 ppm and contributed to inhibition of
      butyric fermentation and retardation of aerobic spoilage. HLC was considered to
      be 3-HPA from its absorption spectrum. These results suggest that the production
      of 3-HPA by Lb. coryniformis 394 is useful in ensiling and that the modified
      colorimetric method is effective to detect 3-HPA in silage.

PMID- 19584560
TI  - TBK1-targeted suppression of TRIF-dependent signaling pathway of Toll-like
      receptors by 6-shogaol, an active component of ginger.
AB  - Toll-like receptors (TLRs) are primary sensors that detect a wide variety of
      microbial components involving induction of innate immune responses. After
      recognition of microbial components, TLRs trigger the activation of myeloid
      differential factor 88 (MyD88) and Toll-interleukin-1 (IL-1) receptor domain
      containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling
      pathways. 6-Shoagol, an active ingredient of ginger, inhibits the MyD88-dependent
      signaling pathway by inhibiting inhibitor-kappaB kinase activity. Inhibitor
      kappaB kinase is a key kinase in nuclear factor kappaB (NF-kappaB) activation.
      However, it is not known whether 6-shogaol inhibits the TRIF-dependent signaling
      pathway. Our goal was to identify the molecular target of 6-shogaol in the TRIF
      dependent pathway of TLRs. 6-Shogaol inhibited the activation of interferon
      regulatory factor 3 (IRF3) induced by lipopolysaccharide (LPS) and by
      polyriboinosinic polyribocytidylic acid (poly[I:C]), overexpression of TRIF, TANK
      binding kinase1 (TBK1), and IRF3. Furthermore, 6-shogaol inhibited TBK1 activity
      in vitro. Together, these results suggest that 6-shogaol inhibits the TRIF
      dependent signaling pathway of TLRs by targeting TBK1, and, they imply that 6
      shogaol can modulate TLR-derived immune/inflammatory target gene expression
      induced by microbial infection.

PMID- 19584559
TI  - Protective effect of selenoarginine against oxidative stress in D-galactose
      induced aging mice.
AB  - The protective effect of selenoarginine against oxidation resistance was
      investigated in D-galactose (D-gal)-induced aging mice. The mice were divided
      into four groups (n=15): a normal group, a model group, a lowdose selenoarginine
      group (8.35 microg of Se/kg b.w./d), and a high dose selenoarginine group (16.78
      microg of Se/kg b.w./d). The aging model was induced by s.c. injection D
      galactose dissolved in 0.9% normal saline of a dose of 150 mg/kg/d for 6 weeks.
      The mice in the normal group received s.c. injection of sterile normal saline at
      the same dose and frequency. The results showed that oxidative stress in the
      liver, kidney, and brain tissues and the serum of the mice was induced by D
      galactose, but selenoarginine had an obviously protective effect against D
      galactose-induced aging mice. Lowdose selenoarginine performed better than high
      dose selenoarginine. The protective effect of selenoarginine on D-galactose
      induced aging mice can be attributed to elevation of the activity of antioxidase
      and enhanced antioxidant defenses.

PMID- 19584561
TI  - Screening and characterization of potential probiotic lactic acid bacteria from
      cultured common carp intestine.
AB  - Screening of potential probiotic LAB for aquaculture from adult common carp
      intestine was performed seasonally. Lactococcus lactis h2 and Lactococcus
      raffinolactis h47, which show cholic acid resistance and strong antibacterial
      activity against fish pathogens, were selected from predominant LAB in summer and
      winter respectively. Enterococcus pseudoavium h50, with the strongest
      antimicrobial activity among the strains isolated through 1 year, was also
      selected. Streptococcus iniae I1, with strong antimicrobial activity, was
      selected from predominant LAB in young common carp intestine. Direct screening of
      LAB with cholic acid resistance was also carried out seasonally. The
      antibacterial activity of the isolates was tested, and Lactobacillus fuchuensis
      K11 was selected from the summer isolates. In addition, five candidate strains
      were selected from the winter samples. The candidates' levels of cholic acid
      resistance and antibacterial activity were better than or at the least matched
      those of their corresponding type strains. All the candidates grew over a wide
      range of temperatures.

PMID- 19584562
TI  - Mutational analysis of uncharged polar residues and proline in the distal one
      third (Thr130-Pro142) of the highly conserved region of mouse Slc10a2.
AB  - Solute carrier family member 2 (SLC10A2) reabsorbs bile acids at the distal
      terminus of the ileum in an Na(+)-dependent manner. Alignment of deduced amino
      acid sequences of SLC10 family members and homologous genes in various species
      revealed a highly conserved region that corresponds to Gly(104)-Pro(142) of
      SLC10A2. To elucidate the functional importance of this region, uncharged polar
      residues and Pro in the distal one-third of this region in mouse Slc10a2
      (mSlc10a2) were submitted to mutational analysis, and taurocholic acid uptake and
      cell surface localization were evaluated. In addition to mutations that abolished
      almost all of the transport activity with and without cellular localization
      failure (P142V and T130A respectively), a mutation that perhaps affected affinity
      for taurocholic acid was identified (T134A). These results suggest that the
      highly conserved region contains residues involved in the substrate interaction,
      function, and cellular localization of mSlc10a2.

PMID- 19584564
TI  - Myocardial recovery by mechanical unloading with left ventricular assist system.
AB  - It has been generally believed that advanced congestive heart failure (HF) is
      progressive, but there is increasing evidence that mechanical unloading with the
      use of left ventricular assist system (LVAS) occasionally reverses the progress
      of HF and permits device explantation. This "bridge to recovery" strategy is
      attracting interest, not only for the treatment of severe HF, but also in the
      study of the pathophysiological mechanisms involved in remodeling and its
      regression, with the hope of establishing reliable indicators of sustained
      recovery and strategies to enhance this process. Tissue samples obtained at the
      time of LVAS implantation and at explantation enabled study of the effects of LV
      unloading at the cellular and gene levels. However, the problem with these
      analyses is the lack of correlation between clinical improvement and cellular or
      molecular changes. Clinically, there are still many questions about the
      application of this strategy. The evaluation of LV function while on LVAS and the
      prediction of sustained recovery after explantation of the device have been the
      major concerns. Pharmacological regimens to promote recovery have been proposed,
      but require validation by multicenter study. Further investigation of the
      underlying mechanisms may help to establish strategies to enhance the recovery
      process.

PMID- 19584563
TI  - Cyclic dipeptide of D-ornithine obtained from the dobsonfly, Protohermes grandis
      Thunberg.
AB  - A new compound was isolated from the water-soluble fraction of a methyl alcohol
      extract obtained from the larva of the dobsonfly (Protohermes grandis Thunberg).
      The novel compound had a 12-membered ring and was confirmed to be a cyclic
      dipeptide of D-ornithine by a chiral analysis, using high-performance liquid
      chromatography, 2D-nuclear magnetic resonance, and field desorption mass
      spectrometry.

PMID- 19584565
TI  - Dietary effect of capric acid containing soyphospholipids.
AB  - A comparative evaluation of the dietary effect between capric acid (C10:0)
      containing soyphospholipids and soyphospholipids without capric acid on the lipid
      profile of serum of rats when ingested at 5% or 10% level by weight in soybean
      oil was made. Rats were taken in five groups. One group was fed 20% soybean oil.
      Two groups received soybean oil containing 5% and 10% soyphospholipids by weight,
      respectively. Other two groups were fed soybean oil containing 5% and 10% capric
      acid containing soyphospholipids by weight, respectively. The other dietary
      components remained same for all the groups. The feeding was done for 4 weeks. At
      the end of feeding period there was no althrough significant change in weight
      gain, food intake and food efficiency ratio (FER). No significant change was
      observed in serum lipid profiles between the rats fed soybean oil and soybean oil
      with 5% or 10% soyphospholipids. There was significant decrease in serum total
      cholesterol (TC) and high density lipoprotein (HDL)-cholesterol level in the rats
      fed soybean oil blended with capric acid containing soyphospholipids at 5% level.
      The level of TC, triglyceride (TG), very low density lipoprotein (VLDL)
      cholesterol decreased significantly when the rats were fed capric acid containing
      soyphospholipids at 10% level. There is overall significant change in TC, TG,
      VLDL- and LDL-cholesterol. The possible mechanism behind the reduction of serum
      lipid profile may be the reduction of interfacial tension of phospholipids could
      affect serum lipid profiles due to enhanced or much greater extent of
      emulsification of the both polar and nonpolar lipid components and their transfer
      from the intestine to the bile pathway.

PMID- 19584567
TI  - Imaging of metabolites by MALDI mass spectrometry.
AB  - Visualization of endogenous molecules in small experimental animals is very
      important in order to investigate the localization of specific molecules.
      Conventional imaging techniques are not suitable for simultaneous visualization
      of endogenous molecules. We recently developed a new imaging method-imaging mass
      spectrometry (IMS) using matrix-assisted laser desorption/ionization quadrupole
      ion trap time-of-flight (MALDI-QIT-TOF). In this study, we applied IMS using
      MALDI-QIT-TOF to visualize the metabolites in medaka (Oryzias latipes) sections
      and determined the spatial distribution of metabolites including lipids.

PMID- 19584566
TI  - Polymerizable anionic gemini surfactants: physicochemical properties in aqueous
      solution and polymerization behavior.
AB  - A novel polymerizable anionic gemini surfactant has been synthesized and the
      physicochemical properties in aqueous solution have been studied with a
      combination of various analytical techniques. The surfactant (PA12-2-12) contains
      two anionic monomeric parts linked with an ethylene spacer and polymerizable
      methacryloxy groups covalently bound to the terminal of the hydrocarbon chains.
      The static surface tension data suggest that, when compared with a conventional
      (non-polymerizable) anionic gemini surfactant (A12-2-12), (i) the interfacial
      adsorption of PA12-2-12 occurs more effectively from low surfactant
      concentrations, whereas (ii) a weak interaction of the polymerizable terminal
      groups with water molecules (and/or the steric hindrance of the polymerizable
      groups) plays a significant role in the subsequent molecular packing at the
      air/aqueous solution interface. The latter effect (as well as the electrostatic
      repulsion between the anionic headgroups) results in a relatively less packed
      monolayer film, overcoming the strong intermolecular attractive interaction that
      is frequently seen for gemini surfactant systems. In the region of low added
      electrolyte concentrations, PA12-2-12 spontaneously forms spherical micelles in
      aqueous solution, which is confirmed with the Corrin-Harkins analysis (critical
      micelle concentration (cmc) vs. total counter-ion concentration) and cryogenic
      transmission electron microscopy (cryo-TEM). The spherical micelles have been
      polymerized under UV light irradiation in the absence of added electrolytes. Cryo
      TEM measurements confirm that no significant change in the original micelle
      morphology occurs during the polymerization. This offers a possibility that the
      polymerizable anionic gemini surfactant should be useful as nano-structural
      organic templates and/or interfacial stabilizers in aqueous solution.

PMID- 19584568
TI  - Iodine-catalyzed synthesis of five-membered cyclic ethers from 1,3-diols under
      solvent-free conditions.
AB  - Intramolecular etherification of 1,3-diols was investigated using iodine as a
      catalyst under solvent-free conditions. The reaction proceeded to completion in a
      heterogeneous system. Five-membered cyclic ethers were obtained by intramolecular
      cyclization of 1,3-diols with dehydration. A propella ether (11
      oxatricyclo[4.4.3.0(1,6)]tridecane) was conveniently synthesized from a 1,3-diol
      (6-(2-hydroxyethyl)spiro[4.5]decan-6-ol) in 86% yield with carbon skeleton
      rearrangement under the following conditions: a temperature of 60 degrees C, a
      molar ratio of 1,3-diol:iodine = 1:0.2, and a time period of 3 h. Bicyclic ethers
      were also obtained from the corresponding 1,3-diols, but spiro ethers were
      obtained in lower yield. Terpenic cyclic ethers were efficiently synthesized from
      the corresponding 1,3-diols, derived from (+)-camphor and (-)-fenchone. In the
      case of etherification with a mechanism of carbon skeleton rearrangement, the
      yield of the solvent-free reaction was as high as that of the corresponding
      reaction in solution. Etherification reactions with carbon skeleton rearrangement
      proceeded more smoothly than those with hydride shift.

PMID- 19584569
TI  - Protecting effect of phytoncide solution, on normal human dermal fibroblasts
      against reactive oxygen species.
AB  - Four types of phytoncide solutions (A-Type, AB-Type, D-Type and G-Type) was
      evaluated for reduction of cell damage induced by oxidative stress, ultraviolet A
      (UVA), ultraviolet B (UVB), hydroxyperoxide (H2O2) and t-butyl-hydroperoxide (t
      BHP); stimulation of collagen synthesis against UVA irradiation; and inhibition
      of matrix metalloproteinase-1 (MMP-1) activity induced by UVA in human normal
      dermal fibroblasts and human reconstituted skin model. The A-Type, AB-Type, D
      Type and G-Type of phytoncide solutions pretreatment resulted in significant
      protection against cell damage induced by UVB, UVA, H2O2 and t-BHP. The amount of
      type I collagen following UVA irradiation was increased by treatment with
      phytoncide solutions in a concentration-dependent manner. On the other hand,
      phytoncide solutions also suppressed the excess MMP-1 irradiated UVA in a
      concentration-dependent manner. These effects of G-type solution were superior to
      those of other types solutions.

PMID- 19584570
TI  - In vitro eye irritancy test of lauryl derivatives and polyoxyethylene alkyl
      derivatives with the reconstructed rabbit corneal epithelium model.
AB  - The rabbit corneal epithelium model (RCE model) was developed as a three
      dimensional in vitro model to replace animal testing for the assessment of eye
      tolerance. In the model, a stratified culture of rabbit corneal epithelial cells
      is grown at the air-liquid interface on a collagen gel acting as a parabasal
      membrane. Histological cross-sections show that the structure of RCE model
      closely parallels that of the rabbit corneal epithelium. The lauryl derivatives,
      such as sodium lauryl sulfate (SLS), polyoxyethylene (9) lauryl ether (PLE),
      sodium polyoxyethylene (2) lauryl ether sulfate (SPLE), mono glyceryl laurate
      (MGL), and sodium N-lauroyl-L-glutaminate (SLG), and polyoxyethylene alkyl
      derivatives, polyoxyethylene (9) lauryl ether (PLE), polyoxyethylene (10) cetyl
      ether (PCE), polyoxyethylene (10) stearyl ether (PSE), polyoxyethylene (10) oleyl
      ether (POE), and polyoxyethylene (10) behenyl ether (PBE), were evaluated for in
      vitro eye irritation potential using the RCE model by the measurement of
      viability with MTT assay. SLS, PLE, SPLE, MGL, and SLG inhibited 90.3%, 69.8%,
      79.7%, 45.8%, and 32.7% of the viability at a concentration of 0.5%. The IC50
      (50% inhibitory concentration) values of SLS, PLE, SPLE, MGL, and SLG were
      0.086%, 0.205%, 0.133%, 0.627%, and 0.934%, respectively. These results indicated
      that a functional group at the end of lauryl chain is an important factor for
      inhibiting the viability using the RCE model. The polyoxyethylene alkyl
      derivatives had distinctly different the viability potencies according to their
      alkyl patterns. PLE inhibited the viability greater than other polyoxyethylene
      alkyl derivatives. Therefore, the lauryl chain of PLE is an important factor for
      inhibiting the viability on the RCE model.

PMID- 19584571
TI  - In vitro biological activity of Salvia leriifolia benth essential oil relevant to
      the treatment of Alzheimer's disease.
AB  - In this study the chemical composition, cholinesterase inhibitory property and
      anti-inflammatory activity of S. leriifolia Benth. essential oil was evaluated
      for the first time. GC and GC-MS analysis revealed the presence of camphor
      (10.5%), 1,8-cineole (8.6%), camphene (6.2%) and alpha-pinene (4.7%) as main
      constituents. S. leriifolia oil exhibited a promising antioxidant activity by
      DPPH assay with an IC(50) 2.26 microL/mL. Interesting cholinesterase inhibitory
      activity was also found with IC(50) values of 0.32 and 0.29 microL/mL for
      acetylcholinesterase (AChE) and butyrrylcholinesterase (BChE), respectively.
      Moreover, this oil inhibited LPS-induced NO production with an IC(50) value of
      165 microg/mL. The absence of cytotoxicity at 1000 microg/mL was evaluated by MTT
      assay in 142BR cells.

PMID- 19584572
TI  - Acquisition-weighted MRSI for detection and quantification of BNCT 10B-carrier L
      p-boronophenylalanine-fructose complex, a phantom study.
AB  - Proton magnetic resonance spectroscopy (1H MRS) is a potential method to detect
      and quantify a boron neutron capture therapy 10B-carrier compound, L-p
      boronophenylalanine (BPA), in the brain. However, optimal positioning of MRS
      voxel to capture tissue with maximal BPA concentration can be challenging. Three
      dimensional proton magnetic resonance spectroscopic imaging (3D 1H MRSI) provides
      spectral data covering a large spatial volume, which is a major advantage in
      detecting and quantifying BPA. BPA detection limit in phantom conditions was
      determined at 1.5 T using a 3D 1H MRSI protocol with clinically acceptable
      nominal spatial resolution and duration. Quantification tests for aqueous phantom
      were performed using both single voxel MRS and 3D MRSI. In 3D MRSI, BPA detection
      limit was approximately 1.0 mM and BPA quantification accuracy was better than +/
      5%. The results suggest that MRSI would be a feasible method for in vivo BPA
      evaluation in clinical conditions.

PMID- 19584573
TI  - A screening tool for attention deficit hyperactivity disorder in children in
      Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: A clinically validated attention deficit hyperactivity
      disorder (ADHD) scale in Arabic for evaluating children in Saudi Arabia who might
      be suspected of having ADHD is lacking. Thus, we studied the validity of an
      Arabic version of the ADHD Rating Scale in discriminating children with an ADHD
      diagnosis from normal children or from those with non-ADHD psychiatric diagnoses,
      including mental retardation. METHODS: The guardians of 119 children provided
      demographic data and completed the standardized Arabic version of the ADHD Rating
      Scale on their children, who were either normal, had a diagnosis of ADHD, or had
      a non-ADHD psychiatric diagnosis. The mean rating scores of the groups were
      compared, and the cutoff points were calculated for both sexes. RESULTS: The
      scores discriminated children with ADHD diagnosis (mean and [SD], 28 [6.288])
      from normal children (10.93 [8.009]), and those with a non-ADHD psychiatric
      diagnosis (16.63 [8.865]). ADHD cutoff points were obtained for male (23.5) and
      female (22.5) children. Psychosocial characteristics associated with children
      having ADHD were not associated with the diagnosis of ADHD. CONCLUSION: The ADHD
      Rating Scale (Arabic version), in terms of either the grand total score or the
      total score of each of its two subscales, demonstrated concurrent and
      discriminant validity by discriminating children with ADHD from other clinical
      and non-clinical children groups. The study obtained cutoff points for both sexes
      based only on the grand total score of the scale because of the relatively small
      sample size. Replication of the study, utilizing a larger sample and eliciting
      ratings from both parents and teachers, is recommended.

PMID- 19584574
TI  - Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients.
AB  - Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive
      metabolic disorder that results in combined immunodeficiency, neurologic
      dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi
      Arabia or in patients with an Arabic ethnic background. We report on two Saudi
      girls with PNP deficiency. Both showed severe lymphopenia and neurological
      involvement. Sequencing of the PNP gene of one girl revealed a novel missense
      mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT.
      Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly
      reduced, but did not completely eliminate PNP activity.

PMID- 19584575
TI  - Forced eye closure-induced reflex seizure and non-ketotic hyperglycemia.
AB  - We report an uncommon case of 53-year-old female patient with partial seizure
      induced by forced voluntary eye closure due to non-ketotic hyperglycemia. The
      initial laboratory tests showed an elevated blood glucose level of 550 mg/dL but
      no evidence of ketosis. Brain magnetic resonance imaging was normal. When the
      blood glucose levels decreased slowly to about 150 mg/dL in five days, the
      seizures ended completely. No anticonvulsants were used. Since seizures are
      generally refractory to antiepileptic medication, control of blood glucose is
      essential.

PMID- 19584576
TI  - Prevalence of exercise-induced bronchoconstriction in teenage football players in
      Tunisia.
AB  - BACKGROUND AND OBJECTIVES: Studies on exercise-induced bronchoconstriction (EIB)
      in team sports are lacking. The aim of this study was to screen for EIB among
      amateur teenage football players in Tunisia and to compare EIB prevalence between
      regions. METHODS: One hundred ninety-six male football players (mean age [SD],
      13.5 [0.5] yrs), practicing in three different cities of Tunisia (Tunis, Sousse
      and Sfax), underwent an outdoor free run of 7 minutes. Forced expiratory volume
      in one second (FEV subset1) was recorded prior to and at 0, 3, 5, 10, 15, 20 and
      30 minutes after the run. Players were screened for EIB positivity defined as a
      greater than 10% decline in FEV subset1 from the resting value at any timepoint.
      RESULTS: FEV1 decreased more than 10% in 30% of the players. EIB positivity was
      more common in Sfax (15.8%) than in Tunis (7.7%) (P=.03). Air humidity during the
      study was higher in Tunis. CONCLUSION: EIB is prevalent among amateur teenage
      football players in Tunisia. The prevalence differs between regions and seems to
      be dependent on air humidity levels.

PMID- 19584577
TI  - Breast metastasis of small bowel carcinoid tumor misdiagnosed as primary breast
      cancer.

PMID- 19584578
TI  - Experience with oral mexiletine in primary erythromelalgia in children.
AB  - Primary erythromelalgia is characterized by burning pain, redness, and warmth in
      the extremities. We present two cases of primary erythromelalgia both of whom
      presented with a history of several months of severe burning pain in both hands
      and feet. Both patients had received multiple pain medications with no
      improvement in symptoms. Pain was relieved by putting affected parts in ice cold
      water, which resulted in immersion injury of the affected parts. Both patients
      stopped taking part in school and social activities. We tried oral mexiletine, a
      class Ib antiarrythmic agent, in view of its reported role in various chronic
      painful conditions. Dramatic improvement was observed with its use. Both patients
      improved after several weeks of use, and there were fewer soaking episodes. We
      observed no adverse effects with mexilitine therapy.

PMID- 19584579
TI  - A 15-year-old girl with pancytopenia and congenital defects.

PMID- 19584580
TI  - Clinicopathological study of male breast carcinoma: 24 years of experience.
AB  - BACKGROUND AND OBJECTIVES: Because breast cancer in men is rare, few patients are
      available for prospective studies. To learn more about its epidemiology, risk
      factors, clinical features, genetics and pathology in our country, we conducted a
      retrospective study of all cases seen in recent decades at our institution.
      PATIENTS AND METHODS: We identified each case of male breast cancer in the
      database at the Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir,
      India, between the years 1983 to 2007. RESULTS: We identified only 32 cases of
      male breast cancer over the 24-year period. Male breast cancer accounted for 32
      (2.8%) of 1141 resected breast specimens, which included all breast lesions and
      32 (4.1%) of 780 breast cancer cases. Of the 32 cases, 20 (62.5%) had various
      associated risk factors. Invasive ductal carcinoma was seen in 30 cases (93.7%).
      Of 20 cases that underwent molecular studies, 16 (80%) patients had estrogen
      receptor positivity whereas 14 (70%) had progesterone receptor positivity. Six
      cases (30%) overexpressed HER2 and p53. The BRCA2 mutation was observed in 4
      cases (40%) while no patient presented with the BRCA1 mutation. CONCLUSION: An
      incidence of 4.1% for male breast cancer indicates that this disease is not as
      uncommon as presumed in this part of the world. Breast cancer in men seems more
      frequently to be hormone receptor positive and the BRCA2 mutation confers a
      significant risk to men.

PMID- 19584581
TI  - The validity and reliability of the Arabic version of the EQ-5D: a study from
      Jordan.
AB  - BACKGROUND AND OBJECTIVES: EQ-5D is a generic measure that permits comparisons in
      quality of life across disease states, and which may provide useful data for
      health policy and resource allocation decision-making. There are no published
      reports on the acceptability and psychometric properties of the EQ-5D in the
      Arabic language. We therefore investigated the validity and reliability of the
      Arabic translation of the EQ-5D in Jordan. METHODS: The study was conducted on a
      convenience sample consisting of consecutive adult Arabic-speaking outpatients or
      visitors attending a university teaching hospital. Subjects were interviewed
      twice using a standardized questionnaire containing the EQ-5D, Short Form 36
      Health Survey (SF-36). To assess the validity of the Arabic version of the EQ-5D,
      ten hypotheses relating responses to EQ-5D dimensions or the visual analogue
      scale (EQ-VAS) to SF-36 scores or other variables were examined and test-retest
      reliability was assessed. RESULTS: The study included 186 subjects who had a mean
      age of 45.3 years and included 87 (47%) females. The major problem reported in
      more than 102 (55%) of the subjects was anxiety/depression. All of the ten
      apriori hypothesis relating EQ-5D responses to external variables were fulfilled.
      Cohenas k for test-retest reliability (n=52) ranged from 0.48 to 1.0. CONCLUSION:
      The Arabic translation of EQ-5D appears to be valid and reliable in measuring
      quality of life in Jordanian people.

PMID- 19584582
TI  - Factors associated with sexual dysfunction in Jordanian women and their sexual
      attitudes.
AB  - BACKGROUND: Female sexual dysfunction (FSD) is defined as disorders of libido,
      arousal, and orgasm, as well as sexual pain, that leads to personal distress or
      interpersonal difficulties. Social aspects of FSD have been understudied. The aim
      of this study was to explore the social aspects of FSD and sexual attitudes of
      Jordanian women. SUBJECTS AND METHODS: Six hundred thirteen married females were
      studied between October 2006 and August 2007 at the National Center for Diabetes,
      Endocrinology and Genetics (NCDEG), Amman, Jordan. Females were interviewed using
      a special questionnaire that was suitable to our culture and added to the Arabic
      translation of the Female Sexual Function Index (FSFI) Questionnaire. RESULTS:
      Older age was associated with a decreased total FSD index and its domain scores.
      Women with obesity were more likely to have impaired arousability and impaired
      capability of reaching orgasm. About 58.5% of women reported that they prepared
      themselves if they had sexual desire and 68.2% reported wearing special attire
      for this purpose. Only 37.2% of women could ask their husband for a special
      excitement. CONCLUSIONS: FSD is prevalent in Jordan. Its social aspects are
      understudied and need more research in the future.

PMID- 19584583
TI  - RE: Serum viral markers in Iranian patients with congenital bleeding disorder.

PMID- 19584584
TI  - Accuracy of the Fischer scoring system and the Breast Imaging Reporting and Data
      System in identification of malignant breast lesions.
AB  - BACKGROUND AND OBJECTIVES: Fischer developed a scoring system in 1999 that made
      identifying malignnant lesions much easier for inexperienced radiologists. Our
      study was performed to assess whether this scoring system would help beginners to
      accurately diagnose breast lesions on magnetic resonance (MR) imaging and to
      assess the correlation between the magnetic resonance mammography Breast Imaging
      Reporting and Data System (MRM BI-RADS) grade and the final diagnosis. PATIENTS
      AND METHODS: The lesion morphology and contrast kinetics of 63 masses in 41
      patients were evaluated on MRI and accorded a MRM BI-RADS final assessment
      category using the Fischer scoring system. The accuracy was evaluated after the
      final diagnosis was obtained by tissue sampling and follow-up imaging. RESULTS:
      There were 25 malignant and 30 benign lesions. Eight lesions were seen by MRI
      only and we could not verify their pathology since we did not have MR-guided
      biopsy facilities at the time of the study. On MR mammography, the proven
      carcinomatous lesions were characterized as BI-RADS category V in 16 (64%),
      category IV in 7 (28%), and category III in 2 (8%) lesions. Benign lesions were
      graded as category V in 3 (10%), category IV in 6 (20%), and category III in 3
      (10%), category II in 10 (33%) and category I in 8 (27%) lesions. The MRM BI-RADS
      category accurately predicted malignancy in 92% and a benign pathology in 70% of
      the lesions. The overlap between the MRM features of chronic inflammatory lesions
      and carcinomas resulted in a lower accuracy in diagnosing benign as compared to
      malignant lesions. CONCLUSION: The MRM BI-RADS lexicon using the Fischer scoring
      system is useful and has a high predictive value, especially for malignant breast
      lesions, and is easy to apply. Overlapping features between benign inflammatory
      and malignant lesions might yield a reduced accuracy in inflammatory pathologies.

PMID- 19584585
TI  - Anthropometry and body composition of school children in Bahrain.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted because of the lack of a
      comprehensive nationwide assessment of data on the anthropometric status and
      related health problems in Bahraini school children aged 6 to 18 years. SUBJECTS
      AND METHODS: A cross-sectional survey was conducted on the anthropometric status
      of school children enrolled in the primary, intermediate and secondary government
      schools in all populated regions of Bahrain. The sample size included 2594
      students (1326 girls and 1268 boys) representing 2.5% of the total student
      population. For sample selection, a multi-stage sampling design was chosen that
      combined multi-cluster and simple random sampling methods. Anthropometric
      measurements included height, weight, mid-arm circumference and skin fold
      thickness at two sites (triceps and subscapular). Anthropometric indices derived
      were body mass index (BMI) and arm muscle area. The WHO reference standards
      (2007) and the National Health and Nutrition Examination Survey (NHANES) II data
      were used for comparison. RESULTS: Compared to WHO reference standards, the
      median height of Bahraini children and adolescents in the age range of 6 to 18
      years was close to the 25th percentile or lower, while the median BMI during
      adolescent years was comparable in boys, but higher than WHO standards in girls,
      reaching the 75th percentile. The cutoff values of BMI for overweight/obesity
      status (85th and 95th percentile) were higher by 3-6 kg/m(2) compared to WHO
      standards. While skin fold thicknesses were also higher in Bahraini adolescents
      compared to their American counterparts (NHANES II), arm muscularity was
      substantially lower. CONCLUSIONS: Current study findings for BMI as well as skin
      fold thicknesses suggest an increased trend toward adiposity among Bahraini
      adolescents, especially in girls, which puts this age group at a high risk of
      adult obesity and its consequences. A need for urgent intervention programs is
      emphasized.

PMID- 19584586
TI  - Prevalence of psychological symptoms in Saudi secondary school girls in Abha,
      Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Adolescence is characterized by rapid physiological,
      social and cognitive changes. Aim of the present work is to study mental health
      of Saudi adolescent secondary school girls in Abha city, Aseer region, Saudi
      Arabia. METHODS: A cross-sectional study was conducted in 10 secondary schools
      for girls using the Arabic version of the symptom-revised checklist 90 (SCL 90
      R), a mental health questionnaire that was administered to the girls by fourth
      year female medical students. RESULTS: The most prevalent mental symptoms in the
      545 female students were phobic anxiety (16.4%), psychoticism (14.8%), anxiety
      (14.3%), and somatization (14.2%). The prevalence of depression, paranoid
      ideation and interpersonal sensitivity amounted to 13.9%, 13.8% and 13.8%,
      respectively. The least prevalent mental symptoms were hostility (12.8%) and
      obsessive-compulsive behavior (12.3%). Overall, psychological symptoms (in terms
      of a positive global severity index) were found in 16.3% of the girls. In a
      multivariate logistic regression analysis, no significant relationship was found
      with sociodemographic factors. CONCLUSION: Psychological symptoms and disorders
      are prevalent in secondary school girls and health professionals need to be able
      to recognize, manage and follow-up mental health problems in young people.
      Further research is needed to explore the magnitude of the problem at the
      national level.

PMID- 19584587
TI  - Doppler ultrasonography in the diagnosis of Graves disease: a non-invasive,
      widely under-utilized diagnostic tool.

PMID- 19584590
TI  - Bibliography. Current world literature. Drugs in anesthesia,.

PMID- 19584592
TI  - Current world literature.

PMID- 19584593
TI  - Lipid management in clinical practice.

PMID- 19584594
TI  - The expanding role of complement in adipose tissue metabolism and lipoprotein
      function.

PMID- 19584595
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 19584596
TI  - Not all angiopoietin-like proteins (Angptls) are created equal: insights from
      molecular, genetic, and pharmacological studies on the mechanism of LPL
      inhibition by Angptl3 and Angptl4.

PMID- 19584598
TI  - Current Opinion in Neurology. Current world literature.

PMID- 19584599
TI  - Sports medicine pearls and pitfalls: benign neutropenia in athletes.

PMID- 19584601
TI  - Legal ergogenic aids?

PMID- 19584602
TI  - Exercise in the treatment and prevention of diabetes.
AB  - The inclusion of regular physical activity is critical for optimal insulin action
      and glycemic control in individuals with diabetes. Current research suggests that
      Type II diabetes mellitus can be prevented and that all types of diabetes can be
      controlled with physical activity, largely through improvements in muscular
      sensitivity to insulin. This article discusses diabetes prevention and the acute
      and chronic benefits of exercise for individuals with diabetes, along with the
      importance and impact of aerobic, resistance, or combined training upon glycemic
      control. To undertake physical activity safely, individuals also must learn
      optimal management of glycemia.

PMID- 19584603
TI  - Effects of exercise on quality of life and prognosis in cancer survivors.
AB  - Cancer is a global health problem with over 10 million cancer survivors in the
      United States alone. Cancer and its treatments often produce side effects that
      undermine quality of life. The purpose of this article is to review research
      examining the effects of physical activity (PA) upon quality of life and disease
      prognosis in cancer survivors. We divide our review into PA studies focusing upon
      (a) quality of life during treatments, (b) quality of life during survivorship
      (after treatments), (c) quality of life during palliative care, and (d) disease
      prognosis end points. Compelling clinical trial data indicate that PA can improve
      quality of life end points during treatment and survivorship. Data during
      palliative care is limited. Observational data suggest that PA may reduce the
      risk of disease recurrence and extend survival in some cancer survivors. Research
      findings suggest that PA is an appropriate recommendation for most cancer
      survivors, although many research questions remain.

PMID- 19584604
TI  - Night eating syndrome presenting as anorexia in an athlete: case report and
      review.

PMID- 19584605
TI  - Legal nutritional boosting for cycling.
AB  - Several nutritional strategies have been used in cycling to improve performance.
      Carbohydrate feeding during exercise has been shown to be effective, but recent
      studies have suggested that recommendations may have to be adjusted to take into
      account recent findings. Protein co-ingested with carbohydrate during exercise
      has received a lot of recent interest, but the evidence is equivocal, at best.
      Thus, in the absence of a plausible mechanism, it is difficult to see how protein
      would increase endurance performance. There also has been a lot of interest in
      training with low glycogen to maximize training adaptations, but the longer-term
      effects upon performance are still unclear. Various supplements have been
      suggested to improve endurance performance, but most of these nutrition
      supplements lack the scientific support that would warrant the recommendation.

PMID- 19584606
TI  - The influence of nutritional ergogenic aids on exercise heat tolerance and
      hydration status.
AB  - Exercise in the heat may predispose an athlete to an exertional heat illness. It
      is imperative to be knowledgeable on the influence of various nutritional
      supplements on exercise tolerance and hydration status. Because of the variety of
      nutritional ergogenic aids that are easily accessible to athletes, medical and
      health professionals must rely on empirical evidence when making conclusions
      about the efficacy of a supplement while not ignoring significant anecdotal
      reports that may resemble real-life situations more closely.

PMID- 19584607
TI  - Supplements: help, harm, or hype? How to approach athletes.
AB  - Supplement use by athletes presents many challenges to health care professionals.
      We need to respect the athlete's desire to optimize performance and balance this
      with the need to protect the athlete's health. Supplements are available so
      readily and hold significant appeal because of the promise of quick results with
      little effort. Because we work with athletes who may have underlying health
      issues that could be compromised by misdirected supplement use, we need to ask
      the questions: what do you take, how much, and how often. Why must we do this?
      Our goal is to help our athletes strive, thrive, and stay alive.

PMID- 19584608
TI  - Effects of the dietary flavonoid quercetin upon performance and health.
AB  - There is increased interest among such diverse groups as the military, athletes,
      and the aged for novel plant-derived dietary supplements to enhance performance
      and maintain/improve health. Quercetin, a flavonoid found in fruits and
      vegetables, has unique biological properties that are likely to improve
      mental/physical performance and reduce infection risk during intense exercise.
      These properties include antiinflammatory, antioxidant, and psychostimulant
      activity, as well as the ability to stimulate mitochondrial biogenesis, and they
      form the basis for potential benefits to overall health and disease resistance.
      However, most information regarding quercetin is based upon in vitro and animal
      studies. Therefore, there is a pressing need for well-designed clinical trials to
      evaluate this novel dietary supplement further. This article will examine the
      recent scientific literature concerning the role of quercetin in mental and
      physical performance and health.

PMID- 19584609
TI  - ACSM Clinician Profile. David T. Bernhardt, M.D.

PMID- 19584610
TI  - To use or not to use: the dilemma of NSAIDs and craniotomy.

PMID- 19584612
TI  - Use of glyceryl trinitrate patches in the treatment of accidental digital
      injection of epinephrine from an autoinjector.

PMID- 19584613
TI  - Intestinal perforation caused by three small magnets.

PMID- 19584614
TI  - Malposition of nasogastric tube detected by a multislice computed tomography.

PMID- 19584615
TI  - Progress in the making.

PMID- 19584617
TI  - Vascular conditions causing vision disorders. Preface.

PMID- 19584618
TI  - Carotid artery dissection and vertebrobasilar insufficiency.

PMID- 19584619
TI  - Cerebral blindness.

PMID- 19584620
TI  - Mitochondrial disorders.

PMID- 19584621
TI  - Ischemic optic neuropathy.

PMID- 19584623
TI  - Arteriovenous malformations and carotid-cavernous fistulae.

PMID- 19584622
TI  - Retinal vascular occlusion syndromes.

PMID- 19584624
TI  - Diagnostic techniques in neurovascular disorders.

PMID- 19584625
TI  - Neuro-ophthalmic aspects of aneurysms.

PMID- 19584626
TI  - Visual dysfunction in migraine.

PMID- 19584627
TI  - Transient visual loss.

PMID- 19584629
TI  - Giant asymptomatic pericardial cyst.
AB  - Pericardial cysts are rare. We provide high-quality imagery demonstrating a giant
      cyst using plain radiography, ultrasound and magnetic resonance imaging (MRI).

PMID- 19584630
TI  - Quantitative regional blood flow measurements in exercising leg skeletal muscle
      based on 99mTc-pertechnetate clearance.

PMID- 19584631
TI  - Traumatic bronchobiliary fistula diagnosed by 99mTc-mebrofenin hepatobiliary
      scintigraphy.

PMID- 19584633
TI  - Cor pulmonale due to congenital central hypoventilation syndrome presenting in
      adolescence.
AB  - OBJECTIVE: To report the first case of congenital central hypoventilation
      syndrome (CCHS) presenting with severe cor pulmonale in an adolescent. METHODS
      AND DESIGN: Case report and literature review. Our Institutional Review Board
      waived the need for consent. SETTING: Pediatric intensive care unit in a tertiary
      care children's hospital. PATIENT: A 12-year-old girl who developed profound
      hypoxia following routine dental extraction under intravenous opiate sedation and
      became progressively obtunded due to marked hypoventilation without hypoxic
      arousal, requiring mechanical ventilation. She had evidence of severe right heart
      failure, but no cardiac, pulmonary, neurologic, or neuromuscular cause was
      identified. The diagnosis of CCHS was suspected and subsequently confirmed by
      blood polymerase chain reaction analysis that revealed a heterozygous polyalanine
      expansion mutation of the PHOX2B gene (five polyalanine repeats). CONCLUSIONS:
      This report describes the unusual presentation of severe cor pulmonale in an
      adolescent with so-called "late-onset" CCHS. CCHS was previously thought to be a
      disease affecting only neonates, but the late-onset phenotype has now been well
      described in adults. It should be considered in any child presenting with
      unexplained right heart failure without an identifiable cause, particularly if
      central sleep apnea is present, because early initiation of ventilatory support
      can prevent cardiac and neurologic sequelae and improve outcome.

PMID- 19584634
TI  - Chronic granulomatous disease presenting as fulminant Aspergillus pneumonitis: a
      lethal combination?
AB  - OBJECTIVE: Case reports of two patients with unusually late initial presentation
      of chronic granulomatous disease with fulminant Aspergillus pneumonia. DATA
      SOURCES AND EXTRACTION: Medical notes; retrospective study. STUDY SELECTION:
      Identical pattern of clinical presentation in two patients referred for support
      with extracorporeal membrane oxygenation (ECMO). Our Institutional Review Board
      waived the need for consent. DATA SYNTHESIS: Two school-aged boys presented with
      features of, and were initially treated, for community-acquired pneumonia.
      However, the disease course was rapidly progressive to fulminant respiratory
      failure and because both failed conventional intensive care management, they were
      referred to ECMO support. Although both died of evolving multiorgan failure, ECMO
      support allowed open lung biopsy leading to diagnosis of invasive Aspergillus
      pneumonia and chronic granulomatous disease. CONCLUSIONS: Failure of adequate
      therapy for acute community-acquired pneumonia and rapid progression to
      respiratory failure should lead to the possibility of fungal etiology. Congenital
      immunodeficiency may present for the first time late in life, so acute invasive
      pulmonary aspergillosis in the absence of known risk factors should lead to
      consideration of chronic granulomatous disease regardless of patient age.

PMID- 19584635
TI  - Entrapment of a subclavian venous catheter in a child--how to get it out?
AB  - OBJECTIVE: To report a rare case of an entrapped subclavian venous catheter and
      to describe an anatomically based maneuver to remove it. DESIGN: Case report.
      SETTING: Pediatric critical care unit in a tertiary care hospital. PATIENT: An 8
      yr-old girl suffering from 50% body surface area burns and clinical sepsis in
      whom a double lumen subclavian venous catheter, placed 12 days earlier, could not
      be removed. INTERVENTION: Concomitant abduction and internal rotation of the
      shoulder and outward traction in the scapular plane plus backward pressure on the
      first rib while carefully pulling out the entrapped catheter. RESULT: Successful
      removal of the intact catheter, avoiding catheter disruption and embolization.
      CONCLUSION: Side hole of an acutely placed multilumen catheter may be entrapped
      at the costoclavicular angle. An anatomically-based maneuver may widen the gap
      between the clavicle and the first rib and enable safe removal of the catheter.

PMID- 19584637
TI  - Pediatric neurointensive care: 2008 update for the Rogers' Textbook of Pediatric
      Intensive Care.
AB  - OBJECTIVE: To review important articles, in the field of pediatric neurointensive
      care, that were published subsequent to the fourth edition of the Rogers'
      Textbook of Pediatric Intensive Care. DATA SOURCES: The U.S. National Library of
      Medicine (http://www.ncbi.nlm.nih.gov/sites/entrezPubMed) was searched for the
      term pediatric and the following individual terms, cardiac arrest, asphyxia,
      traumatic brain injury, status epilepticus, stroke, cerebral ischemia, and
      cerebral hemorrhage, to generate abstracts of additional citations that were then
      screened for potential inclusion. The authors were also aware of a number of key
      recent articles in both pediatric and adult neurointensive care and these were
      also screened. STUDY SELECTION AND DATA EXTRACTION: Promising articles were
      reviewed and the decision as to whether they were included was made at the
      discretion of the section editors. DATA SYNTHESIS: Articles in four categories
      were included based on selected chapters in the neurointensive care section of
      the textbook, using the specific chapter heading in the textbook, namely, head
      and spinal cord trauma, hypoxic-ischemic encephalopathy, status epilepticus, and
      cerebrovascular disease and stroke. CONCLUSION: Developments in the field and
      practice of pediatric neurocritical care continue with significant additions to
      the literature and practice recommendations concerning care following traumatic
      brain injury, cardiac arrest, status epilepticus, and cerebrovascular events.
      Importantly, the continued progression in knowledge raises the health services
      issue of whether, in certain settings of high clinical volume, it is time for
      specialized pediatric neurointensive care services or units.

PMID- 19584638
TI  - Minimizing and accounting for the impact of rescue therapies in clinical trials.

PMID- 19584639
TI  - Extracorporeal cardiopulmonary resuscitation for in-hospital cardiac arrest:
      lessons from acute neurotoxicity.

PMID- 19584640
TI  - Management of pediatric traumatic brain injury in France--Clarity required.

PMID- 19584641
TI  - Validating serologic biomarkers of brain injury for cardiac arrest research.

PMID- 19584642
TI  - Organ donation performance in critical care.

PMID- 19584643
TI  - Pressure-volume curves and ventilator tuning in acute respiratory distress
      syndrome.

PMID- 19584644
TI  - Extracorporeal membrane oxygenation for refractory septic shock in children: One
      institution's experience.

PMID- 19584645
TI  - Serum cardiac troponin I levels in pediatric sepsis/septic shock.

PMID- 19584647
TI  - Pharmacologic vitreolysis--premise and promise of the first decade.

PMID- 19584648
TI  - Intravitreal injection of therapeutic agents.
AB  - BACKGROUND: Intravitreal injection (IVI) with administration of various
      pharmacological agents is a mainstay of treatment in ophthalmology for
      endopthalmitis, viral retinitis, age-related macular degeneration, cystoid
      macular edema, diabetic retinopathy, uveitis, vascular occlusions, and retinal
      detachment. The indications and therapeutic agents are reviewed in this study.
      METHODS: A search of the English, German, and Spanish language MEDLINE database
      was conducted. A total of 654 references spanning the period through early 2008
      were individually evaluated. RESULTS: The advantage of the IVI technique is the
      ability to maximize intraocular levels of medications and to avoid the toxicities
      associated with systemic treatment. Intravitreal injection has been used to
      deliver several types of pharmacological agents into the vitreous cavity:
      antiinfective and antiinflammatory medications, immunomodulators, anticancer
      agents, gas, antivascular endothelial growth factor, and several others. The goal
      of this review is to provide a detailed description of the properties of numerous
      therapeutic agents that can be delivered through IVI, potential complications of
      the technique, and recommendations to avoid side effects. CONCLUSION: The IVI
      technique is a valuable tool that can be tailored to the disease process of
      interest based on the pharmacological agent selected. This review provides the
      reader with a comprehensive summary of the IVI technique and its multitude of
      uses.

PMID- 19584649
TI  - Safety and efficacy of intravitreal bevacizumab (avastin) for the management of
      branch and hemiretinal vein occlusion.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab
      (Avastin, Genentech) for the treatment of macular edema (ME) secondary to branch
      retinal vein occlusion (BRVO) and hemiretinal vein occlusion (HRVO). METHODS: A
      retrospective review was performed of consecutive patients treated with
      intravitreal bevacizumab (1.25 mg) for ME secondary to BRVO/HRVO from May 2005 to
      August 2006 with follow-up through February 2007. Re-treatment was performed at
      monthly or longer intervals at the discretion of the treating physician. RESULTS:
      Fifty-two eyes with a BRVO and 13 eyes with an HRVO received intravitreal
      bevacizumab at baseline. Visual acuity improved by a mean of 12 letters at 1
      month (n = 51; P < 0.001), 13 letters at 3 months (n = 61; P < 0.001), 13 letters
      at 6 months (n = 42; P < 0.001), 14 letters at 9 months (n = 27; P < 0.001), and
      15 letters at 12 months (n = 17; P = 0.015). The mean optical coherence
      tomography (OCT) thickness decreased by 184 microm (P < 0.001), 131 microm (P <
      0.001), 161 microm (P < 0.001), 158 microm (P = 0.002), and 205 microm (P =
      0.002) at 1 month, 3 months, 6 months, 9 months, and 12 months, respectively. The
      mean number of injections was 1.4, 2.1, 2.7, and 3.1, and 3.3 at 1 month, 3
      months, 6 months, 9 months, and 12 months, respectively. No ocular or systemic
      adverse events were observed. CONCLUSION: Improvements in visual acuity and OCT
      outcomes were observed during the first year after intravitreal bevacizumab in
      patients with ME secondary to BRVO and HRVO.

PMID- 19584650
TI  - Visual outcomes and incidence of recurrent vitreous hemorrhage after vitrectomy
      in diabetic eyes pretreated with bevacizumab (avastin).
AB  - PURPOSE: To evaluate the safety and effect of bevacizumab pretreatment on the
      incidence of recurrent vitreous hemorrhage and visual acuity after vitrectomy for
      proliferative diabetic retinopathy. METHODS: This was a consecutive,
      retrospective, and comparative cohort study. Patients undergoing vitrectomy from
      September 2006 through November 2007 at the Emory Eye Center for complications of
      proliferative diabetic retinopathy were identified and reviewed. A total of 33
      eyes pretreated with bevacizumab and 104 untreated eyes were observed for
      postoperative vitreous hemorrhage and final visual acuity. RESULTS: Patients in
      the bevacizumab group were significantly younger than those in the untreated
      group (average age, 46.4 vs. 58.4 years) and were more likely to have 20-gauge
      instrumentation (58% vs. 36%). An average of 9.6 days passed between injection
      and surgery. Early (4-6 weeks) rebleed rates were 15% versus 13% in the
      bevacizumab and untreated groups, respectively, and not statistically different.
      Preoperative (7/200 vs. count finger at 4'), 1-month postoperative (20/200(-3)
      vs. 20/150), and 3-month postoperative visual acuity (20/100(-3) vs. 20/100(+2))
      were not statistically different between groups. No statistical difference was
      found in rebleed rates regarding the gauge of vitrectomy. CONCLUSION: Bevacizumab
      pretreatment for diabetic vitrectomy was not associated with any observed
      complications but did not influence rates of postoperative vitreous hemorrhage or
      final visual acuity in this retrospective series. The overall incidence of
      postoperative early vitreous hemorrhage in this series was 13% and seems lower
      than historically reported rates.

PMID- 19584651
TI  - Retinal vein occlusion and low-dose fibrinolytic therapy (R.O.L.F.): a
      prospective, randomized, controlled multicenter study of low-dose recombinant
      tissue plasminogen activator versus hemodilution in retinal vein occlusion.
AB  - PURPOSE: To investigate the efficacy of intravenous thrombolysis with low-dose
      recombinant tissue plasminogen activator (rt-PA) in recent-onset central retinal
      vein occlusion (CRVO) or branch retinal vein occlusion. METHODS: This was a
      prospective, randomized, controlled multicenter trial in patients with CRVO or
      branch retinal vein occlusion, best-corrected visual acuity < or =20/50, and
      onset of symptoms within 11 days before treatment. In each group, patients were
      randomized to either hemodilution or thrombolysis with 50 mg of rt-PA with
      concomitant intravenous heparinization. The primary clinical outcome measure was
      improvement in best-corrected visual acuity from baseline at 1 year. RESULTS:
      Fifty-two subjects were enrolled in the study. Patients with CRVO (n = 41) who
      were treated with rt-PA exhibited a significant improvement in best-corrected
      visual acuity compared with those who received hemodilution (P < 0.0001). At 1
      year follow-up, the proportion of eyes with CRVO achieving an improvement in
      visual acuity of three or more lines was 45% after treatment with rt-PA and 21%
      after hemodilution therapy. The median final best-corrected visual acuity among
      CRVO patients given rt-PA was 20/60 (light perception, 20/15) compared with
      20/400 (light perception, 20/20) in the hemodilution group. There were no
      significant differences among patients with branch retinal vein occlusion (n =
      11). We observed no serious adverse events. No significant differences were found
      regarding the development of ocular neovascularization. CONCLUSION: Treatment
      with intravenous low-dose rt-PA improved visual outcome in CRVO. Thrombolysis was
      not associated with a lower risk of ocular neovascularization, indicating that
      the mechanisms involved in this process occur at an early stage.

PMID- 19584652
TI  - Bevacizumab in macular edema: functional and anatomic changes in a prospective
      case series.
AB  - OBJECTIVE: To evaluate the early rate of change of best-corrected visual acuity
      (BCVA), central retinal sensitivity, neuroretinal and choroidal thickness in
      patients with macular edema after 1.25 mg/0.05 ml intravitreal bevacizumab
      (Avastin; Genentech, Inc., South San Francisco, CA). METHODS: A prospective,
      nonrandomized, interventional study. Thirty-seven consecutive eyes with macular
      edema were included in the study. For all eyes, BCVA, central retinochoroidal
      thickness at standardized A-scan, central retinal thickness, and central retinal
      sensitivity recorded with a spectral scanning laser ophthalmoscope optical
      coherence tomography/microperimeter device were evaluated at baseline and 7, 15,
      30, 37, 45, and 60 days after initial treatment. All patients received 2
      intravitreal bevacizumab injections at 1-month interval. RESULTS: A significant
      although not related improvement of BCVA and retinal sensitivity was seen after 1
      month and 2 months of follow-up. Anatomic improvement only involved the
      neuroretina, although significant changes of central choroidal thickness were not
      detected. CONCLUSION: Intravitreal bevacizumab for macular edema determines
      significant early functional and anatomic improvements.

PMID- 19584653
TI  - Single-session photodynamic therapy combined with intravitreal bevacizumab for
      retinal angiomatous proliferation.
AB  - PURPOSE: To evaluate the efficacy of single-session photodynamic therapy (PDT)
      combined with intravitreal bevacizumab (IVB) in the treatment of retinal
      angiomatous proliferation (RAP) in age-related macular degeneration. METHODS: In
      this pilot study, eight patients with RAP underwent indocyanine green angiography
      (ICGA)-guided single-session verteporfin PDT followed by intravitreal bevacizumab
      (1.25 mg) within a 0-day +/- 1-day interval. All patients were naive to
      treatment. Best-corrected visual acuity (BCVA), fluorescein angiography, ICGA,
      and optical coherence tomography (OCT) were performed at baseline and at each
      follow-up visit. All patients received three consecutive monthly IVB injections;
      thereafter, retreatment with bevacizumab was performed in the case of worsening
      BCVA or a deterioration of angiographic or OCT findings. RESULTS: All patients
      had 9 months of follow-up. Complete resolution of angiographic leakage was
      achieved in all eyes at 9 months. A significant improvement in the mean BCVA was
      observed at 1 month, 3 months, 6 months, and 9 months after combined treatment (P
      = 0.004). Visual acuity improved in 62.5% and was stable in 37.5% of cases. No
      patients had a decrease in BCVA of three or more lines during follow-up. Mean
      central macular thickness was significantly reduced in all patients (P < 0.0001)
      as controlled at 1-month, 3-month, 6-month, and 9-month intervals from initial
      treatment. The mean number of injections for the 9 months were 3.2 +/- 0.4. No
      ocular complications or systemic events developed. CONCLUSION: Sequenced combined
      treatment with single-session PDT and IVB injections may be useful in treating
      RAP, reducing or eliminating retinal edema, and improving or stabilizing visual
      acuity. Further investigations are warranted to outline the appropriate treatment
      paradigm for combination therapy.

PMID- 19584654
TI  - Assessment of optic nerve cup-to-disk ratio changes in patients receiving
      multiple intravitreal injections of antivascular endothelial growth factor
      agents.
AB  - PURPOSE: To assess whether the transient intraocular pressure rise, frequent
      intraocular pressure fluctuations, or antivascular endothelial growth factor
      (VEGF) effects of repeated intravitreal injection of anti-VEGF agents can lead to
      changes in the optic nerve vertical cup-to-disk ratio (C/D). METHODS: Patients
      with a known history of glaucoma and those receiving triamcinolone acetonide were
      excluded from the study. Fundus photographs were cropped to optic disk images
      only, which were then randomized and independently graded by two glaucoma
      specialists. In patients who received treatments in only one eye, the fellow eye
      was used as a control. RESULTS: Twenty-three eyes of 21 patients met inclusion
      criteria. The mean change in C/D was -0.012 (95% confidence interval [CI], -0.053
      to 0.029) for the treated group and -0.006 (95% CI, -0.106 to 0.095) for the
      control group, with no statistically significant difference (P = 0.90). The mean
      change in C/D for eyes receiving < or =5 injections (n = 9) was 0.003 (95% CI, 
      0.089 to 0.095) in the treated group and 0.054 (95% CI, -0.033 to 0.142) in the
      control group, with no statistically significant difference (P = 0.33). In eyes
      receiving >5 injections (n = 14), the mean change in C/D was -0.021 (95% CI, 
      0.095 to 0.052) in the treated group and -0.057 (95% CI, -0.231 to 0.116) in the
      control group, with no statistically significant difference (P = 0.70).
      CONCLUSION: There was no statistically significant change in the vertical C/D of
      optic nerves in patients receiving multiple intravitreal injections of anti-VEGF
      agents, regardless of whether they received fewer or more than five total
      injections. This suggests that the short-term intraocular pressure rise and
      frequent intraocular pressure fluctuation, as well as the anti-VEGF properties of
      these drugs, do not adversely change the optic nerve C/D. Additional prospective
      studies are warranted to confirm these conclusions.

PMID- 19584655
TI  - Complement Factor P in choroidal neovascular membranes of patients with age
      related macular degeneration.
AB  - PURPOSE: To evaluate whether complement Factor P (properdin) was present in
      surgically removed choroidal neovascular membranes of patients with age-related
      macular degeneration (AMD) and to investigate whether associated pre- and
      postoperative clinical characteristics can be correlated. METHODS: The study
      population consisted of 26 AMD patients (26 eyes) with the exclusion criterion of
      prior treatment of the choroidal neovascular membranes. Factor P was detected
      immunocytochemically on paraffin sections (7 microm) by a polyclonal rabbit
      antihuman antibody. RESULTS: Eleven of 22 assessable membranes showed a positive
      reaction for Factor P. The average percentage of Factor P-positive cells per
      membrane ranged from 0.65% to 4.09%. The duration of visual loss was
      significantly longer (8.6 +/- 2.7 vs. 3.9 +/- 0.8 months), and the size of
      postoperative measured area of atrophic retinal pigment epithelium was larger
      (27.6 +/- 7.6 vs. 15.0 +/- 6.9 mm2) in patients with Factor P-positive membranes
      compared with Factor P-negative ones. CONCLUSION: Factor P was expressed in 50%
      of choroidal neovascular membranes of patients with AMD. The group with Factor P
      positive membranes differed significantly from the Factor P-negative group in key
      clinical outcomes. Additional studies need to investigate the role of Factor P in
      the development of AMD for potential therapeutic intervention.

PMID- 19584656
TI  - Macular thickness measurements in normal eyes with time-domain and Fourier-domain
      optical coherence tomography.
AB  - PURPOSE: To compare macular thickness measurements using time-domain optical
      coherence tomography (OCT) and Fourier-domain OCT. METHODS: Thirty-two eyes from
      32 normal patients underwent complete ophthalmic evaluation. Macular scanning
      using the StratusOCT and the RTVue-100 OCT were performed for a total of three
      times each on the same visit. The average retinal thicknesses of the nine macular
      sectors as defined by the Early Treatment Diabetic Retinopathy Study, along with
      the foveal center point and macular volume, were recorded. The SD, the
      coefficient of variation, and the intraclass correlation coefficient were
      calculated for each parameter studied. Comparisons were made between the two OCTs
      in terms of retinal thicknesses measurements, their reproducibility, and macular
      regional differences. Correlations between retinal thickness and demographic
      variables (age and gender) were also investigated. Due to known differences in
      segmentation algorithms of the two OCTs, software calipers were used to measure
      the distance from the internal limiting membrane to the photoreceptor inner
      segment-outer segment junction at the foveal center point on all RTVue scans to
      allow a more fair comparison. RESULTS: The RTVue yielded greater retinal
      thickness measurements in nearly all macular subfields compared with the
      StratusOCT. Even after accounting for differences in segmentation algorithms,
      significant disparities were still evident with the RTVue measurements less than
      those of the StratusOCT at the foveal center. On both machines, the macula was
      thinnest at the fovea and thickest within the 3 mm ring. There were some
      consistent regional variations in macular thickness evident on both OCTs.
      Compared with the StratusOCT, the RTVue generally had lower coefficients of
      variation and higher intraclass coefficients, suggesting better reproducibility.
      Age and gender also appeared to be important determinants in some macular
      thickness parameters. CONCLUSION: Compared with StratusOCT, the RTVue fourier
      domain OCT yields greater retinal thickness measurements with greater
      reproducibility, presumably due to different segmentation algorithms, increased
      sampling density, and greater resolution. However, regional differences across
      the macula can be consistently observed with both devices.

PMID- 19584657
TI  - Spectral domain optical coherence tomography characteristics of cuticular drusen.
AB  - PURPOSE: To evaluate the appearance of cuticular drusen with spectral domain
      optical coherence tomography. METHODS: Eyes of patients with cuticular drusen
      were imaged using a prototype spectral domain optical coherence tomography
      instrument with 5-microm axial resolution. Thickness maps were obtained after
      automated segmentation of the internal limiting membrane and retinal pigment
      epithelium layers using a proprietary algorithm. The volume of subretinal fluid
      (SRF) was calculated using a manual segmentation technique that involved drawing
      boundaries around the SRF. The repeatability of these measurements was tested by
      comparing the volume measurements from multiple scans performed on the same day
      in four eyes of three patients. RESULTS: Sixteen eyes from eight patients with
      cuticular drusen were scanned. Areas of decreased retinal thickness overlying
      drusen were best visualized using the three-dimensional retinal thickness map.
      The distribution and sawtooth pattern of cuticular drusen were best visualized
      using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes,
      13 had SRF within the macula. In the eyes with macular SRF, characteristic
      excrescences were present along the outer retina and attenuation of the
      photoreceptor inner and outer segment boundary were observed in many areas. In
      areas where the retina was detached, the retinal pigment epithelium-Bruch's
      membrane complex appeared nodular or attenuated. The volumetric measurements of
      the SRF were performed using a manual segmentation with a 1.11% mean difference
      between repeated measurements on the same day (range, 0.47-1.68%; standard
      deviation, 0.55%). CONCLUSION: The sawtooth pattern of drusen and the presence of
      excrescences along the detached outer retina are characteristic features of
      cuticular drusen that should be helpful in confirming the diagnosis of this
      condition. The volumetric analysis of the SRF is repeatable and may be useful in
      following the clinical course of these patients.

PMID- 19584658
TI  - Distortion maps from preferential hyperacuity perimetry are helpful in monitoring
      functional response to Lucentis therapy.
AB  - PURPOSE: To use preferential hyperacuity perimetry to obtain a quantitative
      measure of central visual field distortion that would aid in the monitoring of
      functional responsiveness to ranibizumab treatment. METHODS: This study is a
      retrospective analysis of data from patients with neovascular age-related macular
      degeneration treated with ranibizumab. Preferential hyperacuity perimetry (PHP)
      were performed before and within 10 days of treatment. Pre- and posttreatment PHP
      metamorphopsia maps of contours showing 6 levels of metamorphopsia severity (S1
      through S6; least to most distortion) were analyzed. Optical coherence tomography
      (OCT) outputs were subjected to standardized grading to generate metrics on
      subretinal fluid height, maximum retinal thickness, outer high-reflectivity band
      thickness, and height of pigment epithelial detachment (OCT metrics). RESULTS:
      Complete data were available from 17 patients. Statistically significant
      reductions were seen between baseline and posttreatment in PHP contour areas and
      OCT metrics, except for maximum retinal thickness. Mean best-corrected visual
      acuity improved by two letters, but this was not statistically significant.
      Change in PHP parameters correlated strongly with change in subretinal fluid
      height, with P values of <0.01 for most comparisons. Change in best-corrected
      visual acuity did not correlate with change in any of the OCT metrics or PHP
      distortion map areas. CONCLUSION: The reduction in the contour map area seen on
      PHP outputs occurs rapidly and correlates with the resolution of subretinal
      fluid, suggesting that this parameter may be used to monitor response to therapy.

PMID- 19584659
TI  - Endophthalmitis caused by proteus species: antibiotic sensitivities and visual
      acuity outcomes.
AB  - PURPOSE: The purpose of this study was to report the clinical presentation,
      causative organisms, antibiotic sensitivities, management, and visual acuity
      outcomes in patients with endophthalmitis caused by Proteus species at a
      university teaching hospital over a 24-year period. METHODS: This was a
      retrospective consecutive case series. The Bascom Palmer Eye Institute
      Microbiology Laboratory database was reviewed to identify all patients with
      intraocular cultures positive for Proteus species between 1983 and 2007. Clinical
      records were reviewed to ascertain the clinical presentation, management, and
      visual acuity outcomes. RESULTS: In the 13 patients identified, all cases
      followed intraocular surgery, and 1 was associated with a recurrent corneal
      ulcer. Of the 1,751 organisms isolated from intraocular culture during the study
      period, 244 were Gram negative. Proteus species represented 5.3% of gram-negative
      organisms and <1% of the total isolates identified. Endophthalmitis developed 2
      days to 14 days postoperatively (median, 3.5 days), and patients were observed 1
      month to 61 months after presentation (median, 17 months). Presenting vision
      ranged from light perception to 20/200. Ten patients had positive cultures for
      Proteus mirabilis, and three patients had a growth of Proteus morganii. Four
      patients (31%) were infected with >1 organism. All Proteus isolates were
      sensitive to the antibiotics clinically administered, including cefazolin,
      ceftazidime, gentamicin, and the fluoroquinolones. Five patients (38%) initially
      received intravitreal injections of antibiotics alone, 1 received an anterior
      chamber washout in combination with intravitreal injections, and 7 patients (54%)
      received pars plana vitrectomy in combination with intravitreal injections. Two
      of the patients (15%) who received vitrectomies had either an intraocular lens or
      retained nuclear fragments removed. Six patients (46%) received additional
      antibiotic injections during the clinical course, and 6 patients (46%) underwent
      additional surgical procedures. Final visual acuity was better than light
      perception in 5 patients (38%) and was light perception or no light perception in
      8 patients (62%). Only 4 patients (31%) had a final vision acuity > or =5/200.
      CONCLUSION: Despite prompt treatment with appropriate antibiotics, the clinical
      outcome for Proteus species endophthalmitis is often poor.

PMID- 19584661
TI  - Patterns of referral of retinal patients for low vision intervention in the anti
      VEGF era.
AB  - PURPOSE: The goal of this study was to see how the availability of ranibizumab
      affected the referral patterns for low vision (LV) evaluation. METHODS: This
      study used a retrospective review and a comparison of all patients newly referred
      from retinal Practice 1 (J.T.T., R.N.S.) for LV consultation, from July 2005 to
      June 2006 (Year 1, preranibizumab) and from July 2006 to June 2007 (Year 2,
      ranibizumab available), and a retrospective review of patients referred by
      retinal Practice 2 (M.J.E.) since February 2007. RESULTS: Practice 1: In Year 1,
      24 patients with choroidal neovascularization were referred for LV, and in Year
      2, only 12 were referred. There was a trend for those patients referred in Year 2
      to have worse visual acuity and Pelli-Robson contrast sensitivity than those in
      Year 1. In Years 1 and 2, 18 and 11 patients with other conditions were referred
      for LV consultation, respectively. For these patients without choroidal
      neovascularization, there was no significant difference between groups for visual
      acuity or contrast sensitivity. Practice 2: The mean best-corrected visual acuity
      of patients with bilateral choroidal neovascularization referred was 20/145, and
      no patient had visual acuity > or =20/100. CONCLUSION: Although the use of
      antivascular endothelial growth factor agents puts visual acuity in a zone more
      favorable for successful LV intervention, patients with better acuities may not
      be referred for LV evaluation despite their residual visual impairments and their
      scotomas, and despite the fact that without LV intervention, they are having
      difficulty with reading and other activities of daily living. The frequent visits
      required for monthly injection, the tendency to wait until a course of therapy is
      complete before referring patients, and a lesser appreciation for the need for LV
      intervention in patients with only moderate visual loss may be factors in
      explaining this.

PMID- 19584660
TI  - Structural assessment of hyperautofluorescent ring in patients with retinitis
      pigmentosa.
AB  - PURPOSE: To analyze the retinal structure underlying the hyperautofluorescent
      ring visible on fundus autofluorescence in patients with retinitis pigmentosa.
      METHODS: Twenty-four eyes of 13 patients with retinitis pigmentosa, aged 13 years
      to 67 years, were studied. The integrity of the photoreceptor cilia, also known
      as the inner/outer segment junction of the photoreceptors, the outer nuclear
      layer, and retinal pigment epithelium, was evaluated outside, across, and inside
      the ring with spectral-domain optical coherence tomography (OCT). RESULTS: Inside
      the foveal area, fundus autofluorescence did not detect abnormalities. Outside
      the ring, fundus autofluorescence revealed hypoautofluorescence compatible with
      the photoreceptor/retinal pigment epithelium degeneration. Spectral-domain OCT
      inside the ring, in the area of normal foveal fundus autofluorescence, revealed
      an intact retinal structure in all eyes and total retinal thickness values that
      were within normal limits. Across the ring, inner/outer segment junction
      disruption was observed and the outer nuclear layer was decreased in thickness in
      a centrifugal direction in all eyes. Outside the hyperautofluorescent ring, the
      inner/outer segment junction and the outer nuclear layer appeared to be absent
      and there were signs of retinal pigment epithelium degeneration. CONCLUSION:
      Disruption of the inner/outer segment junction and a decrease in outer retinal
      thickness were found across the central hyperautofluorescent ring seen in
      retinitis pigmentosa. Outer segment phagocytosis by retinal pigment epithelium is
      necessary for the formation of an hyperautofluorescent ring.

PMID- 19584663
TI  - Early postoperative intraocular pressure after 23-gauge sutureless small-incision
      pars plana vitrectomy.

PMID- 19584664
TI  - Diagnostic and therapeutic challenges: panuveitis and optic neuritis.

PMID- 19584662
TI  - New technique for inserting 27-gauge twinlight chandelier illumination fibers
      into the eye using intravenous cannula.

PMID- 19584665
TI  - The microcannula ring: 25-gauge infusion cannula stabilizer.

PMID- 19584666
TI  - Re: Surgical treatment of a juxtapapillary retinal hemangioma.

PMID- 19584668
TI  - Re: Macular structure and vision of patients with macular heterotopia secondary
      to retinopathy of prematurity.

PMID- 19584669
TI  - Re: The potential of pluripotent cells in vitreoretinal diseases.

PMID- 19584673
TI  - Antihypertensives for kidney transplant recipients: systematic review and meta
      analysis of randomized controlled trials.
AB  - In nontransplant populations, effects of different antihypertensive drug classes
      vary. Relative effects in kidney transplant recipients are uncertain. We
      performed a systematic review including random effects meta-analysis of
      randomized controlled trials, using Cochrane Collaboration methodology. We
      identified 60 trials, enrolling 3802 recipients. Twenty-nine trials (2262
      patients) compared calcium channel blockers (CCB) with placebo or no treatment,
      10 trials (445 patients) compared angiotensin-converting enzyme inhibitors (ACEi)
      with placebo or no treatment, and seven studies (405 patients) compared CCB with
      ACEi. CCB compared with placebo or no treatment (plus additional agents in either
      arm as required) reduced graft loss (risk ratio [RR] 0.75, 95% confidence
      intervals [CI] 0.57-0.99) and improved glomerular filtration rate (GFR; mean
      difference [MD] 4.5 mL/min, 95% CI 2.2-6.7). Data on ACEi versus placebo or no
      treatment were inconclusive for GFR (MD -8.1 mL/min, 95% CI -18.6-2.4) and
      inconsistent for graft loss, precluding meta-analysis. In direct comparison with
      CCB, ACEi decreased GFR (MD 11.5 mL/min, 95% CI 7.2-15.8), proteinuria (MD 0.28
      g/day, 95% CI 0.10-0.47), hemoglobin (MD 11.5 g/L, 95% CI 7.2-15.8), and
      increased hyperkalemia (RR 3.7, 95% CI 1.9-7.7). Graft loss data were
      inconclusive (RR 7.4, 95% CI 0.4-140). These data suggest that CCB may be
      preferred as first-line agents for hypertensive kidney transplant recipients.

PMID- 19584672
TI  - Intravenous immunoglobulin a natural regulator of immunity and inflammation.
AB  - Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma
      and have been used for the treatment of primary immunodeficiency disorders for
      more than 25 years. IVIG products are also effective in the treatment of
      autoimmune and inflammatory disorders; however, the precise mechanism(s) of
      action is not known. Recent investigations suggest that IVIG has a much broader
      ability to regulate cellular immunity including innate and adaptive components.
      IVIG is also a recently recognized modifier of complement activation and injury.
      Here, we discuss these important advancements and how this knowledge applies to
      desensitization protocols and to the treatment of antibody-mediated rejection.

PMID- 19584674
TI  - Will improved donor safety increase liver donations?

PMID- 19584675
TI  - Comparable barriers to access to kidney transplantation across national lines.

PMID- 19584676
TI  - A lifetime versus a graft life approach redefines the importance of HLA matching
      in kidney transplant patients.
AB  - INTRODUCTION: Human leukocyte antigen (HLA) matching has been de-emphasized in
      the allocation of renal allografts and further discounting is planned in the new
      United Network of Organ Sharing kidney allocation model. An unforeseen
      consequence of poorer matching could be increased sensitization for candidates
      pursuing retransplantation. METHODS: We examined candidates listed in the United
      States from 1988 to 2007 from the Scientific Renal Transplant Registry (SRTR)
      database that were relisted after loss of a primary kidney transplant (n=15,980).
      The primary outcome was change in panel reactive antibody (PRA) from prior to
      recipient's initial transplant to the subsequent listing. Absolute change in PRA
      levels were examined in general linear models and the likelihood of becoming
      newly sensitized in logistic models. RESULTS: There was no appreciable change in
      PRA for patients receiving a first 0 HLA-A, -B, -DR, or 0 HLA-A, -B-mismatched
      kidney transplant; contrariwise, there was a significant increase in PRA by
      increasing HLA mismatch of the first transplant. Only 10% of patients became
      sensitized after a 0 HLA-A, -B-mismatched transplant, whereas the proportion rose
      up to 37% with increasing HLA mismatches. Other factors, notably younger age and
      African American race, also contributed to a higher PRA at relisting.
      CONCLUSIONS: Although there might be a limited impact of HLA matching on acute
      rejection and graft survival, many patients might be negatively impacted from
      poor HLA matching of their first kidney transplant when needing a second
      transplant. This might be particularly important in patients with a long life
      expectancy because of the high likelihood of needing a second transplant during
      their lifetime.

PMID- 19584678
TI  - Real-time bioluminescence imaging of macroencapsulated fibroblasts reveals
      allograft protection in rhesus monkeys (Macaca mulatta).
AB  - BACKGROUND: Encapsulation of cells has the potential to eliminate the need for
      immunosuppression for cellular transplantation. Recently, the TheraCyte device
      was shown to provide long-term immunoprotection of murine islets in a mouse model
      of diabetes. In this report, translational studies were undertaken using skin
      fibroblasts from an unrelated rhesus monkey donor that were transduced with an
      HIV-1-derived lentiviral vector expressing firefly luciferase permitting the use
      of bioluminescence imaging (BLI) to monitor cell survival over time and in a
      noninvasive manner. METHODS: Encapsulated cells were transplanted subcutaneously
      (n=2), or cells were injected without encapsulation (n=1) and outcomes compared.
      BLI was performed to monitor cell survival. RESULTS: The BLI signal from the
      encapsulated cells remained robust postinsertion and in one animal persisted for
      up to 1 year. In contrast, the control animal that received unencapsulated cells
      exhibited a complete loss of cell signal within 14 days. CONCLUSIONS: These data
      demonstrate that TheraCyte encapsulation of allogeneic cells provides robust
      immune protection in transplanted rhesus monkeys.

PMID- 19584677
TI  - Cytoplasmic inheritance of transplantation antigens in animals produced by
      nuclear transfer.
AB  - BACKGROUND: Nuclear transfer has been used as a means of selectively modifying
      the mammalian genome. One possible consequence of this technology is that the
      oocytes used in nuclear transfer may provide additional antigens by cytoplasmic
      inheritance of maternally derived, mitochondrial DNA (mtDNA). These studies
      examine the potential consequences of such inheritance in a large animal
      transplantation model. METHODS: Renal transplants were performed between major
      histocompatibility complex (MHC)-identical animals differing only in the source
      of their maternally derived cytoplasmic DNA, using a protocol, which uniformly
      leads to tolerance within standard MHC-inbred lines. In an attempt to correlate
      transplant results with a putative marker for disparities in cytoplasmically
      inherited minor histocompatibility antigens, we examined one hypervariable region
      of mtDNA, designated hypervariable region 1 (HV1). RESULTS: The mtDNA sequence of
      the HV1 region was found to be invariant among MGH miniature swine of different
      haplotypes, despite 25 years of selective breeding of the sublines of this
      colony. In contrast, swine derived by nuclear transfer into outbred oocytes
      differed in the HV1 region sequence from each other and from MGH swine. Renal
      transplants from standard, inbred MGH swine to their MHC-identical knockout
      counterparts derived from outbred oocytes were rejected within 2 weeks, whereas
      transplants in the reverse direction were accepted for over 30 days. CONCLUSIONS:
      The HV1 sequence of mtDNA may serve as a marker for the level of diversity of
      mtDNA. These transplant data are consistent with the existence of mtDNA-encoded
      mitochondrial minor antigens with a level of diversity that can influence the
      outcome of renal transplantation.

PMID- 19584679
TI  - Comparison of the population capacity of hematopoietic and mesenchymal stem cells
      in experimental colitis rat model.
AB  - OBJECTIVE: This study compares the population and repair ability of bone marrow
      hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) in experimental
      colitis (EC) rat model after allogeneic stem-cell transplantation (SCT). METHODS:
      EC was induced by 2, 4, 6-trinitrobenzenesulfonic acid (TNBS). The HSCs, MSCs,
      HSCs+MSCs, derived from male Sprague-Dawley rats, were cultured and labeled with
      bromodeoxyuridine and then transplanted into the EC rat. The colon samples were
      collected for histologic evaluation at days 7, 14, and 21 posttransplantation.
      Immunohistochemical staining, polymerase chain reaction, and fluorescence in situ
      hybridization were used to detect donor stem cells population. RESULTS: EC
      induced by TNBS had characteristics similar to those of Crohn's disease. A large
      number of bromodeoxyuridine- labeled HSCs or MSCs were detected on days 7, 14,
      and 21 posttransplantation. Sex-determining region of Y chromosomes (sry) was
      found in all EC regions, but not in control and normal tissues. A clear
      localization of Y chromosomes in the colons of EC rat was detected by
      fluorescence in situ hybridization. Immunohistochemical staining revealed that
      HSCs or MSCs had similar population ability. When HSCs and MSCs were combined,
      gross morphologic scores significantly improved 21 days post-SCT compared with
      the control without SCT, but only slightly better than that of HSCs or MSCs
      alone. CONCLUSIONS: Allogeneic transplantation of HSCs or MSCs alone could
      populate in the injured regions of the colons, both showed similar population
      ability in the colons of the TNBS-induced EC model rats. Combination
      transplantation of HSCs with MSCs could improve the gross morphologic scores of
      EC.

PMID- 19584680
TI  - Prevention of early loss of transplanted islets in the liver of mice by
      adenosine.
AB  - BACKGROUND: The low efficiency of islet transplantation necessitating sequential
      transplantations with the use of 2 to 3 donors for a recipient has been a major
      obstacle facing clinical islet transplantation. We determined whether adenosine
      has any beneficial effects on preventing early loss of transplanted islets in the
      liver, thereby facilitating successful islet transplantation from one donor to
      one recipient in mice. METHODS: Two hundred islets, the number of islets from a
      single mouse pancreas, were grafted into the liver of streptozotocin-induced
      diabetic C57BL/6 mice. Adenosine was administered once at the time of islet
      transplantation. Mononuclear cells in the liver of mice receiving islets were
      isolated and examined by flow cytometry. RESULTS: A single injection of adenosine
      at the time of transplantation ameliorated hyperglycemia of diabetic mice
      receiving 200 syngenic islets with suppression of interferon (IFN)-gamma
      production of hepatic NKT cells and neutrophils, while that of control did not.
      The IFN-gamma production of NKT cells and neutrophils in the liver of mice
      treated with alpha-galactosylceramide, a synthetic ligand of NKT cells was
      suppressed by adenosine. The beneficial effect of adenosine was also observed for
      BALB/c islet allografts when alloimmune rejection was prevented by anti-CD4
      antibody. CONCLUSIONS: Adenosine suppresses the NKT cell-mediated IFN-gamma
      production of neutrophils in the liver of mice receiving islets, thus leading to
      prevention of early loss of transplanted syngenic and allogenic islets. The
      findings indicate that adenosine may improve efficiency of clinical islet
      transplantation.

PMID- 19584681
TI  - Type 2 diabetes mellitus phenotype and graft survival after islet
      transplantation.
AB  - BACKGROUND: Body fat accumulation decreases insulin sensitivity. It has being
      associated with earlier onset of type 1 diabetes mellitus (DM) and islet graft
      failure. The aim of this study was to evaluate whether insulin resistance,
      characterized by risk factors for type 2 DM, can predict islet graft survival in
      type 1 DM islet transplant (ITx) recipients. METHODS: Demographic,
      anthropometrical, and laboratory data, as well as family history of type 2 DM
      (first degree relatives), were collected from 44 ITx recipients. Risk factors for
      type 2 DM, such as positive family history of type 2 DM (n=11) and overweight
      (body mass index >25 kg/m2; n=14), were analyzed separately and in combination,
      which was designated as "type 2 DM phenotype" (n=5). Differences in outcomes
      (time-to-graft dysfunction and failure) were compared using Kaplan-Meier curves.
      Cox regression analysis was performed to control for possible confounding
      factors. RESULTS: Neither positive family history of type 2 DM nor overweight at
      baseline could predict islet function outcomes after ITx. However, when both risk
      factors were grouped, the "type 2 DM phenotype" was associated with earlier islet
      graft failure (mean estimate graft survival 25.7+/-9.1 vs. 54.1+/-5.2 months,
      P=0.022). These results were sustained after adjustments for confounding
      variables (OR 5.20, 95% CI 1.12-24.0). CONCLUSIONS: Predisposition for type 2 DM
      can coexist with the type 1 DM phenotype and is associated with earlier decline
      in islet graft function. Prospective clinical trials should address whether it is
      associated with decreased insulin sensitivity and if insulin sensitizers play a
      role in prolonging islet graft survival.

PMID- 19584682
TI  - Tacrolimus-induced elevation in plasma triglyceride concentrations after
      administration to renal transplant patients is partially due to a decrease in
      lipoprotein lipase activity and plasma concentrations.
AB  - BACKGROUND: Hyperlipidemia is a frequent and persistent complication in solid
      organ transplant recipients, leading to the high occurrence of cardiovascular
      disease in this patient population. Lipid abnormalities including increased total
      cholesterol, triglycerides (TG), and low-density lipoprotein-cholesterol have
      been reported frequently in transplantation patients and a variety of
      immunosuppressive therapies seem to be one of the main factors that influence
      posttransplant lipidemic profiles. For many years, tacrolimus (TAC) has been used
      as an immunosuppressive drug in transplantation. The aim of our investigation was
      to determine the effect of TAC administration on the plasma lipid profile and
      some key regulatory proteins of plasma lipid metabolism including cholesterol
      ester transfer protein, hepatic lipase and lipoprotein lipase (LPL) within renal
      transplant patients. METHODS: Twenty-five renal transplant patients were
      recruited and received TAC therapy, of which nine of these patients were treated
      with statin therapy for dyslipidemia. The effects of TAC on plasma total
      cholesterol, TG, HDL-C, low-density lipoprotein-cholesterol, cholesterol ester
      transfer protein, hepatic lipase and LPL concentration and activity were
      determined from patients plasma samples collected before the transplant surgery
      (baseline), and weekly for four consecutive weeks after surgery and TAC
      administration. RESULTS: We observed that TAC significantly increases plasma TG
      concentrations and reduces LPL plasma concentration and activity in renal
      transplant patients, independent of any lipid lowering drug treatment patients
      received. CONCLUSIONS: Taken together, these findings suggest that the reduction
      in LPL activity, partly due to the decrease of plasma LPL concentration after TAC
      administration may be an explanation for hypertriglyceridemia observed in
      patients administered TAC.

PMID- 19584684
TI  - CMV mismatch does not affect patient and graft survival in UK renal transplant
      recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is one of the major infections encountered
      posttransplantation. UK Guidelines (2003) recommend CMV prophylaxis or screening
      with preemptive treatment for all high risk recipients. Studies predating the
      widespread use of CMV prophylaxis have shown that CMV seronegative recipients (R
      ) receiving a renal allograft from a CMV seropositive donor (D+) have worse
      outcomes than those avoiding primary CMV infection. Therefore, it has been
      suggested that CMV matching should be a part of the UK national deceased donor
      kidney allocation scheme. METHODS: We examined patient and allograft survival
      according to donor and recipient CMV serostatus in 10,190 UK adult and pediatric
      deceased donor renal transplant recipients transplanted between 2000 and 2007. We
      also ascertained CMV prophylaxis strategies in all UK renal transplant units.
      RESULTS: Twenty-one of the 22 UK renal transplant centers used prophylactic oral
      valganciclovir for 3 months posttransplant in the D+R- transplants, having done
      so for a median of 4 years. Unadjusted data showed that D+R+ rather than D+R-
      transplants had the lowest patient and allograft survivals at 3 years
      posttransplant. However, after adjustment for donor age, there was no significant
      effect of donor and recipient CMV serostatus on allograft or patient survival.
      CONCLUSIONS: These findings suggest that in an era where CMV prophylaxis is used
      routinely in D+R- transplants, the previously noted adverse effects of primary
      CMV infection on allograft and patient survival can be avoided (perhaps through a
      reduction in the incidence and/or severity of primary CMV infection), without
      using a CMV-matching allocation scheme.

PMID- 19584683
TI  - Incidence of delayed graft function and wound healing complications after
      deceased-donor kidney transplantation is not affected by de novo everolimus.
AB  - BACKGROUND: Concerns about delayed graft function (DGF) and wound healing
      complications with sirolimus has led to suggestions that everolimus introduction
      could be delayed after transplantation. METHODS: In a prospective, multicenter,
      open-label study, deceased-donor kidney transplant recipients at protocol
      specified risk of DGF (defined as > or =1 dialysis session during the first week
      posttransplant excluding day 1) were randomized to start everolimus therapy on
      day 1 posttransplant (immediate everolimus [IE]), or from week 5 (delayed
      everolimus [DE]) with mycophenolic acid until everolimus was initiated. All
      patients received anti-interleukin-2 receptor antibodies, cyclosporine A, and
      corticosteroids. A planned 3-month analysis from this 12-month study is presented
      here. RESULTS: One hundred and thirty-nine patients were randomized (IE 65, DE
      74). The primary composite endpoint: biopsy-proven acute rejection, graft loss,
      death, DGF, wound healing events, or lost to follow-up at month 3, occurred in 36
      IE patients (55.4%) and 47 DE patients (63.5%, P=0.387). The incidence of DGF was
      similar between groups (IE 24.6%, DE 24.3%; n.s.). Wound healing events of any
      type occurred in 40.0% and 41.9% of IE and DE patients (n.s.); events relating to
      initial transplant surgery occurred in 36.9% IE patients and 37.8% DE patients
      (n.s.), most of which were fluid collections. Study drug was discontinued due to
      adverse events or graft loss in 13 IE (20.0%) and 17 DE patients (23.0%).
      CONCLUSIONS: Findings from this randomized, multicenter trial indicate that
      kidney function recovery, wound healing, efficacy, and tolerance are similar at 3
      months posttransplant with immediate or DE in patients at protocol-specified risk
      of DGF.

PMID- 19584685
TI  - Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a
      case-control study.
AB  - BACKGROUND: The specific role of different immunosuppressive agents as risk
      factors for BK virus nephropathy (BKN) has not been well studied. METHODS: In
      this case-control study, we examined the association of tacrolimus (TAC),
      mycophenolate mofetil (MMF), and prednisone with BKN in renal allograft
      recipients transplanted between 1997 and 2004 at our center who underwent
      biopsies for allograft dysfunction. Drug levels or doses were recorded during the
      3 months before the index biopsy. Random effects logistic modeling was used for
      data analysis. RESULTS: There were 33 cases with BKN, biopsied at 16.4+/-2.8
      months and 66 matched controls with biopsies at 21.5+/-2.1 months posttransplant
      (P=0.16). After adjusting for sex, race, retransplant status, diabetes, donor
      source, and induction agent, TAC blood level was associated with increased risk
      of BKN (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.02-1.7, P=0.03),
      whereas MMF dose was not (OR 1.0, 95% CI 0.99-1.0, P=0.2). Moreover, prednisone
      dose was also found to be a significant risk factor for BKN (OR 1.22, 95% CI 1.04
      1.4, P=0.02). CONCLUSIONS: The results of this study show that BKN is associated
      with TAC level and prednisone dose and not with MMF dose. This suggests that
      reducing TAC and prednisone dose and maintaining MMF may be a more appropriate
      initial approach for the treatment of BKN. Further studies are needed to compare
      the efficacy and safety of this approach with the currently recommended one.

PMID- 19584687
TI  - Factors that influence access to the national renal transplant waiting list.
AB  - BACKGROUND: Registry data can be used to examine whether there are differences
      between individual renal units in the proportion of dialysis patients listed for
      renal transplantation, to investigate possible reasons for any differences
      observed, and to discover whether highlighting these anomalies can influence
      practice. METHODS: A cross-sectional study of 12, 401 prevalent adult dialysis
      patients from 41 renal units across England and Wales was performed. The
      proportion of patients registered on the deceased donor transplant waiting list
      was determined for each renal unit. Patient- and center-specific factors that
      influence the probability of being listed for transplantation were identified and
      used to adjust for differences observed between units. The annual change in the
      size of the transplant waiting list was examined before and after presentation of
      these data. RESULTS: A total of 23.3% of patients were active on the transplant
      waiting list. PATIENT: Specific variables significantly associated with listing
      were age, primary renal disease, graft number, social deprivation, and ethnicity
      but not gender. Centre-specific variables included size of renal unit, size of
      living donor program, and listing practice for living donor transplantation.
      Whether the renal unit was also a transplant unit was not significant. After
      adjusting for these variables, there remained unexplained variation between renal
      units in the proportion of dialysis patients on the waiting list. An increase in
      the number of patients listed for transplantation has been observed since
      presenting these data. CONCLUSIONS: Differences in listing practice exist between
      centers that cannot be explained by the patient case mix or center
      characteristics examined.

PMID- 19584686
TI  - Sustained BK viruria as an early marker for the development of BKV-associated
      nephropathy: analysis of 4128 urine and serum samples.
AB  - BACKGROUND: BKV reactivation plays the causative role in the development of BKV
      associated nephropathy (BKVAN). Because of the lack of effective therapy, early
      diagnosis of BKV reactivation is paramount for the prevention of BKVAN. Resting
      in uroepithelial cells, BKV is excreted first in urine before it can be detected
      in plasma. The present study analyzed predictive value of BK viruria for the
      development of BK viremia and its possible advantage for the early BKVAN
      prediction. METHODS: Total of 4128 urine and serum samples obtained from renal
      transplant patients were analyzed for BKV positivity by real-time polymerase
      chain reaction in 433 patients in cross-sectional and in 233 patients in
      longitudinal manner, respectively. The prospective longitudinal analysis included
      seven measurements during the first posttransplant year. RESULTS: A total of 7%
      and 19% patients were positive for BKV in serum and urine, respectively.
      Sustained BK viruria showed sensitivity of 100% and specificity of 94% for BK
      viremia and was associated with significantly higher level of BK load than the
      patients with transient viruria (P<0.01). Interestingly, BK viremia was preceded
      by BK viruria: the peak of viral load and number of positive patients appeared
      during the third and fifth posttransplant month for urine and serum,
      respectively. BKVAN diagnosed in 21.4% of patient with persistent BK viruria
      appeared 5 and 11 weeks after BKV reactivation in serum and urine, respectively,
      was detected. CONCLUSION: Sustained BK viruria is a reliable marker allowing an
      early identification of patients at high risk of BKVAN development and therefore
      assure precocious therapeutic interventions.

PMID- 19584688
TI  - Validity and feasibility of transient elastography for the transplanted liver in
      the peritransplantation period.
AB  - BACKGROUND: Transient elastography has recently been suggested to be capable of
      detecting dynamic changes in stiffness that accompanies acute liver damage. Its
      feasibility and usefulness in the perioperative period in living donor liver
      transplantation (LDLT) have not been studied. METHODS: We evaluated 678 liver
      stiffness measurements (LSMs) obtained in the peritransplantation period from 24
      LDLT recipients, 24 corresponding donors (preoperatively only), another five
      donors with a remnant right liver, and three deceased donor liver transplantation
      recipients. The LSM was performed once preoperatively, every morning
      postoperatively until postoperative day 14, and three times a week after that
      until the patient was discharged from the hospital. RESULTS: Overall LSM success
      rate (valid shots/total shots) was 0.929+/-0.119. There was a significant
      negative relationship between the LSM success rate and thoracic belt thickness
      (P<0.0021). The interquartile range to median value rate of LSMs remained high
      (21.1%+/-11.2%) compared with the preoperative values (15.6%+/-8.5%), even 1
      month after the transplantation. Among LDLT recipients (n=24), the LSM value was
      highest in the first postoperative week and declined thereafter. Recipients with
      complications had significantly higher LSM values than those without
      complications in the fourth postoperative week (POW4; P=0.0066) and POW5 or later
      (P=0.0028). All cases of acute cellular rejection had a concomitant sharp rise in
      liver stiffness and a rapidly depleted portal flow. CONCLUSIONS: Despite the high
      variability of the results, transient elastography may be an efficient method for
      monitoring changes in dynamic liver stiffness in the early posttransplant period.

PMID- 19584689
TI  - Donor complications associated with living donor liver transplantation in Japan.
AB  - BACKGROUND: The Japanese Liver Transplantation Society presented its first report
      on donor morbidity in 2003. The Society has been continuing to survey outcomes in
      living liver donors in Japan. METHODS: By using a uniform comprehensive medical
      record review process, data were collected on 3565 living liver donors who had
      donated grafts by the end of December 2006 at 38 Japanese centers. RESULTS:
      Preoperative problems were reported in 2 donors, intraoperative problems in 27,
      and postoperative complications in 270. In total, 299 donors (8.4%) suffered
      complications related to liver donation. Postoperative complications included
      biliary complications in 3.0%, reoperation in 1.3%, severe after-effects in two
      (0.06%), and death (apparently related to donor surgery) in one donor (0.03%).
      The incidence of postoperative complications in left and right lobe donors was
      8.7% and 9.4%, respectively. CONCLUSIONS: The accumulated experience indicates a
      reduction in the incidence of donor complications, especially for right lobe
      resection. One donor death and two cases of severe after effects related to liver
      donation have been reported during 18 years of living donor liver transplantation
      experience in Japan.

PMID- 19584691
TI  - The impact of EBV load on T-cell immunity in pediatric thoracic transplant
      recipients.
AB  - BACKGROUND: Immunologic monitoring of pediatric transplant (Tx) recipients, who
      are at increased risk of Epstein-Barr virus (EBV)-driven posttransplant
      lymphoproliferative disease, is an important goal in clinical transplantation.
      Here, we investigated the impact of EBV load on T-cell immunity from pediatric Tx
      recipients, using clinically applicable tests for improved assessment of T-cell
      immune competence. METHODS: Thirty-five asymptomatic pediatric thoracic Tx
      patients were categorized into three groups according to their EBV load levels as
      follows: undetectable viral load (UVL), chronic low viral load (LVL) and chronic
      high viral load (HVL). Global and EBV-specific T-cell immunity were assessed by
      ATP release using Cylex Immuknow and T Cell Memory assays. RESULTS: UVL patients
      exhibited normal ATP release to Concanavalin A (ConA) and phytohemagglutinin
      (PHA; 190+/-86 ng/mL, 328+/-163 ng/mL) and detectable EBV-specific (37+/-34
      ng/mL) ATP responses. LVL patients displayed significantly stronger responses to
      ConA (373+/-174 ng/mL), PHA (498+/-196 ng/mL) and EBV (152+/-179 ng/mL), when
      compared with UVL or to HVL patients (ConA 185+/-114 ng/mL, PHA 318+/-173 ng/mL,
      and EBV 33+/-42 ng/mL). Moreover, HVL patients displayed significant inverse
      correlation between CD4+ T-cell ATP levels and EBV loads. CONCLUSIONS: Evaluation
      of global and EBV-specific T-cell immunity provides a rapid assessment of
      patients' immune competence. It is still unclear whether selective oversuppressed
      ATP release by CD4+ T cells reflects HVL patients at risk of posttransplant
      lymphoproliferative disease. Further longitudinal studies will determine the
      importance of Immuknow test in identifying asymptomatic HVL patients vulnerable
      to EBV complications.

PMID- 19584690
TI  - Everolimus with reduced cyclosporine versus MMF with standard cyclosporine in de
      novo heart transplant recipients.
AB  - BACKGROUND: Pharmacokinetic modeling supports trough monitoring of everolimus,
      but prospective data comparing this approach versus mycophenolate mofetil (MMF)
      in de novo cardiac transplant recipients are currently unavailable. METHODS: In a
      12-month multicenter open-label study, cardiac transplant patients received
      everolimus (trough level 3-8 ng/mL) with reduced cyclosporine A (CsA) or MMF (3
      g/day) with standard CsA, both with corticosteroids+/-induction therapy. RESULTS:
      In total, 176 patients were randomized (everolimus 92, MMF 84). Mean creatinine
      clearance was 72.5+/-27.9 and 76.8+/-32.1 mL/min at baseline, 65.4+/-24.7 and
      72.2+/-26.2 mL/min at month 6, and 68.7+/-27.7 and 71.8+/-29.8 mL/min at month 12
      with everolimus and MMF, respectively. The primary endpoint was not met since
      calculated CrCl at month 6 posttransplant was 6.9 mL/min lower with everolimus,
      exceeding the predefined margin of 6 mL/min. However, by month 12 the between
      group difference had narrowed versus baseline (3.1 mL/min). All efficacy
      endpoints were noninferior for everolimus versus MMF. The 12-month incidence of
      biopsy-proven acute rejection International Heart and Lung Transplantation grade
      more than or equal to 3A was 21 of 92 (22.8%) with everolimus and 25 of 84
      (29.8%) with MMF. Adverse events were consistent with class effects including
      less-frequent cytomegalovirus infection with everolimus (4 [4.4%]) than MMF (14
      [16.9%], P=0.01). CONCLUSION: Concentration-controlled everolimus with reduced
      CsA results in similar renal function and equivalent efficacy compared with MMF
      with standard CsA at 12 months after cardiac transplantation.

PMID- 19584692
TI  - Effect of adherence to home spirometry on bronchiolitis obliterans and graft
      survival after lung transplantation.
AB  - BACKGROUND: Patient-controlled home spirometry (HS) after lung transplantation
      has been shown to be valid and reliable to detect the presence of graft infection
      and rejection at its earliest onset. Effects of nonadherence to HS on detection
      of the bronchiolitis obliterans syndrome (BOS) and on graft survival are unknown.
      METHODS: A 7-year prospective cohort study assessed nonadherence longitudinally
      using electronic spirometry for 24 months. During follow-up, BOS,
      retransplantation, and survival were stratified by adherence groups. RESULTS:
      Electronic monitoring of 226 patients confirmed that 123,487 measures were
      performed. Period prevalence was 0.76 measures per patient day and decreased
      significantly over time (P<0.0001). During follow-up, BOS was developed in 32% of
      patients; 5% received a second transplant, and mortality rate was 19%. Kaplan
      Meier event-free analysis showed decreased freedom from BOS time in nonadherers
      (30%) compared with good (43%) or moderate adherers (19%) (log rank 6.008;
      P<0.014) and a tendency toward lower retransplantation rates (log rank 3.14;
      P<0.07). Mantel Cox regression revealed no impact of adherence on patient
      survival. CONCLUSIONS: This was the first study assessing nonadherence to HS
      based on electronic monitoring in relation to long-term outcome after lung
      transplantation. Nonadherers showed decreased freedom from BOS in the largest
      sample to date, but did not impact survival.

PMID- 19584693
TI  - Analysis of USRDS: incidence and risk factors for Pneumocystis jiroveci
      pneumonia.
AB  - BACKGROUND: To investigate the effect of modern immunosuppression on the
      incidence, risk factors, morbidity, and mortality of Pneumocystis pneumonia (PCP)
      in recipients of kidney transplants. METHODS: We conducted a retrospective cohort
      study of 32,757 Medicare primary transplant recipients in the United States Renal
      Data System from January 1, 2000 through July 31, 2004. PCP infection was defined
      by Medicare claims using International Classification of Disease, 9th Revision
      codes. The incidence of PCP infections, graft loss, and death were measured.
      RESULTS: There were a total of 142 cases (cumulative incidence 0.4%) of PCP after
      kidney transplantation during the study period. By using multivariate analysis
      with Cox regression, expanded criteria donor, donation after cardiac death, and
      earlier year of transplant were associated with development of PCP disease.
      Induction immunosuppression and acute rejections were not associated with risk
      for PCP infections. However, based on adjusted hazard ratio (AHR), maintenance
      immunosuppression regimens containing the combination of tacrolimus and sirolimus
      (AHR 3.60, confidence interval [CI] 2.03-6.39), Neoral and mycophenolate mofetil
      (AHR 2.09, CI 1.31-3.31), and sirolimus and mycophenolate mofetil (AHR 2.77, CI
      1.40-5.47), were associated with development of PCP. As a time dependent
      variable, PCP was associated with an increased risk of both graft loss and death.
      CONCLUSION: PCP infections are rare in the modern era of prophylaxis; however,
      these infections are a serious risk factor for graft loss and patient death, in
      particular, in patients who are on sirolimus as part of the immunosuppressive
      regimen. The median time to development of PCP after transplant was 0.80+/-0.95
      years, suggesting a longer period of PCP prophylaxis.

PMID- 19584695
TI  - Is a single low-fixed dose of rituximab sufficient for treating acute humoral
      rejection after kidney transplantation?

PMID- 19584696
TI  - Potential risk in using hepatic veins of a native liver for reconstructing
      accessory veins in right lobe living donor graft.

PMID- 19584698
TI  - Interacinar c4d staining in pancreas allografts.

PMID- 19584699
TI  - Correlates of HIV, sexually transmitted infections, and associated high-risk
      behaviors among male clients of female sex workers in Tijuana, Mexico.
AB  - OBJECTIVES: To determine sociodemographic and behavioral correlates of HIV
      infection among male clients of female sex workers (FSWs) in Tijuana. METHODS:
      Four hundred men aged 18 years or older who had paid or traded for sex with a FSW
      in Tijuana during the past 4 months were recruited in Tijuana's 'zone of
      tolerance,' where prostitution is practiced openly under a municipal permit
      system. Efforts were made to balance the sample between residents of the United
      States (San Diego County) and of Mexico (Tijuana). Participants underwent
      interviews and testing for HIV, syphilis, gonorrhea, and Chlamydia. Logistic
      regression identified correlates of HIV infection. RESULTS: Mean age was 36.6
      years. One-quarter had injected drugs within the previous 4 months. Lifetime use
      of heroin, cocaine, and methamphetamine was 36, 50, and 64%, respectively. Men
      had frequented FSWs for an average of 11 years, visiting FSWs an average of 26
      times last year. In the past 4 months, one-half reported having unprotected sex
      with a FSW; 46% reported being high fairly or very often when having sex with a
      FSW. Prevalence of HIV, syphilis, gonorrhea, and Chlamydia was 4, 2, 2.5, and
      7.5%; 14.2% were positive for at least one infection. Factors independently
      associated with HIV infection were living in Mexico, ever using methamphetamine,
      living alone, and testing positive for syphilis. CONCLUSION: Male clients of FSWs
      in Tijuana had a high sex and drug risk profile. Although sexually transmitted
      infection prevalence was lower than among FSWs, HIV prevalence was comparable
      suggesting the need for interventions among clients to prevent spread of HIV and
      sexually transmitted infections.

PMID- 19584700
TI  - Foreskin inflammation is associated with HIV and herpes simplex virus type-2
      infections in Rakai, Uganda.
AB  - DESIGN: We assessed foreskin inflammation associated with HIV and herpes simplex
      virus type 2 (HSV-2) in circumcised men. METHODS: Foreskin tissues were assessed
      in 97 HIV-infected and 135 HIV-uninfected men enrolled in randomized trials of
      circumcision in Rakai, Uganda. Inflammation was quantified using an ordinal score
      evaluating extent, intensity, and cellular composition of infiltrates in the
      epithelium and stroma. Prevalence rate ratios of inflammation were estimated by
      multivariate Poisson regression. RESULTS: Foreskin inflammation was primarily
      focal. Epithelial inflammation was present in 4.2% of men with neither HIV nor
      HSV-2 infection; 7.8% of men with only HSV-2; 19.0% with HIV alone (P = 0.04);
      and 31.6% in HIV/HSV-2 coinfected men [prevalence rate ratio (PRR) 7.5, 95%
      confidence interval (CI) 2.3-23.8, P < 0.001]. Stromal inflammation was present
      in 14.1% of HIV/HSV-2 uninfected men, compared with 29.7% in men with HSV-2 alone
      (P = 0.03), 33.3% in men with HIV alone (P = 0.04), and 61.0% in men with HIV/HSV
      2 coinfection (PRR 4.3, 95% CI 2.3-7.9, P < 0.001). In HIV-infected men,
      epithelial inflammation was associated with higher HIV viral load. Epithelial
      inflammation was more frequent among men reporting recent genital ulceration.
      Both epithelial and stromal inflammation were more common among men with smegma
      on physical examination. CONCLUSION: Foreskin inflammation is increased with HIV
      and HSV-2 infections, higher HIV viral load and presence of smegma. Foreskin
      inflammation may have implications for HIV transmission and acquisition in
      uncircumcised men.

PMID- 19584702
TI  - Comparison of previous and present World Health Organization clinical staging
      criteria in HIV-infected Malawian children.
AB  - In many settings, HIV infected children are looked after with limited access to
      CD4 cell count or viral load. The decision to initiate antiretroviral therapy
      (ART) is made clinically, based on the WHO paediatric staging criteria, which
      were revised in 2006. Results of using new and old criteria were compared. Of 694
      children, 626 (90.2%) fulfilled criteria to start ART when applying the new WHO
      staging guidelines, whereas 330 (47.6%) children were eligible for ART when using
      the old WHO criteria. This signifies a marked rise in the number of paediatric
      patients qualifying for ART on clinical grounds.

PMID- 19584701
TI  - Combination HBV therapy is linked to greater HBV DNA suppression in a cohort of
      lamivudine-experienced HIV/HBV coinfected individuals.
AB  - OBJECTIVES: To determine if highly active antiretroviral therapy (HAART) with
      combination anti-hepatitis B virus (HBV) therapy compared to HAART with HBV
      monotherapy leads to greater HBV DNA suppression in an HIV/HBV coinfected cohort.
      DESIGN: A cross-sectional analysis of 122 HIV/HBV coinfected patients from
      Australia and the United States. METHODS: Univariate analysis and ordinal
      logistic regression were used to determine factors associated with an HBV DNA
      less than 100 IU/ml. RESULTS: The majority of patients were on HAART (85%), had
      an HIV RNA less than 50 copies/ml, a median CD4 cell count of 438 cells/microl,
      and had prior or current lamivudine therapy (98%). The majority (89%) of those on
      HAART were on HBV-active drugs including 54% on tenofovir (TDF) with either
      lamivudine (LAM) or emtrictabine (FTC), 34% receiving LAM or FTC monotherapy, and
      12% on TDF monotherapy. Only 4% of patients in the combination (TDF + LAM/FTC)
      group had HBV DNA greater than 20 000 IU/ml compared to 54% in the group on no
      HBV-active therapy, 31% in the LAM or FTC monotherapy group, and 30% in the TDF
      monotherapy group (P < 0.0001). In an ordinal logistic regression model,
      monotherapy with either TDF or LAM remained independently associated with higher
      HBV DNA. CONCLUSION: These data suggest that there may be an advantage to using
      TDF in combination with LAM or FTC in HIV/HBV coinfection, particularly in the
      setting of previous LAM experience. Continued prospective follow-up in this study
      will confirm whether the advantage is sustained longer-term.

PMID- 19584703
TI  - Impact of adding maraviroc to antiretroviral regimens in patients with full viral
      suppression but impaired CD4 recovery.
AB  - We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on
      antiretroviral therapy with full viral suppression but impaired CD4 cell
      recovery. There were no significant differences in changes in CD4 cell count,
      percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks
      of maraviroc therapy. Plasma endotoxin levels measured in four patients before
      and during maraviroc treatment also showed no significant differences.

PMID- 19584704
TI  - Prevalence of unprotected anal intercourse among HIV-diagnosed MSM in the United
      States: a meta-analysis.
AB  - OBJECTIVE: To integrate the empirical findings on the prevalence of unprotected
      anal intercourse (UAI) among HIV-diagnosed men who have sex with men (MSM) in the
      United States. METHODS: Comprehensively searching MEDLINE, EMBASE, PsycINFO (2000
      2007), hand searching bibliographic lists, and contacting researchers. Thirty US
      studies (n = 18,121) met selection criteria. Analyses were conducted using random
      effects models and meta-regression. RESULTS: The prevalence of UAI was
      considerably higher with HIV-seropositive partners (30%; 95% confidence interval
      25-36) than with serostatus unknown (16%; 95% confidence interval 13-21) or HIV
      seronegative partners (13%; 95% confidence interval 10-16). The prevalence of UAI
      with either a serostatus unknown or HIV-seronegative partner was 26%. The UAI
      prevalence did not differ by the length of the behavioral recall window but did
      vary by the type of anal intercourse (insertive vs. receptive). Studies with the
      following features had a lower UAI prevalence: recruiting participants before
      2000, MSM of color being the majority of study sample, recruiting participants
      from medical settings, using random or systematic sampling methods, and having
      interviewers administer the questionnaire. Being on antiretroviral therapy,
      having an undetectable viral load, and reporting more than 90% medication
      adherence were not associated with UAI. CONCLUSION: Most HIV-diagnosed MSM
      protect partners during sexual activity, but a sizeable percentage continues to
      engage in sexual behaviors that place others at risk for HIV infection and place
      themselves at risk for other sexually transmitted infections. Prevention with
      positives programs continues to be urgently needed for MSM in the United States.

PMID- 19584705
TI  - The impact of AIDS diagnoses on long-term neurocognitive and psychiatric outcomes
      of surviving adolescents with perinatally acquired HIV.
AB  - OBJECTIVE: To explore the association between previous severe HIV disease,
      defined as past Centers for Disease Control and Prevention class C diagnosis, and
      neurocognitive and psychiatric outcomes in long-term survivors of perinatally
      acquired HIV. DESIGN: A retrospective cohort study of perinatally HIV-infected
      adolescents receiving outpatient care at a single site. METHODS: Comparisons were
      made between those with and without class C diagnoses. RESULTS: Eighty-one
      patients formed the study group, 47% were females and 72% were African-American.
      Median patient age was 15 years (interquartile range 13-17). Of the study group,
      47% had a past class C diagnosis. The median age at class C diagnosis was 3.1
      years (interquartile range 0.9-8.1). There were no significant differences
      between the groups with respect to most recent CD4(+) cell percentage or plasma
      viral RNA level. Class C patients were more likely to have a history of
      psychiatric diagnosis [odds ratio 2.6; 95% confidence interval (CI) 1.1-6.3],
      psychiatric hospitalization (odds ratio 4.8; 95% CI 1.2-17.4), or learning
      disability (odds ratio 4.5; 95% CI 1.7-11.4). There was a significant difference
      in full-scale intelligence quotient between the groups (adjusted linear
      regression coefficient -11.7; 95% CI -17.9 to 5.5). After adjusting for age at
      antiretroviral therapy initiation, the associations between class C diagnosis and
      lower full-scale intelligence quotient, learning disorders, and psychiatric
      diagnoses remained significant. CONCLUSION: A distant history of AIDS diagnosis
      was associated with an increased risk of neurocognitive and psychiatric
      impairment in adolescents with perinatally acquired HIV. Further research should
      help delineate if early treatment, possibly soon after birth and definitely prior
      to AIDS diagnosis, might lead to improved outcomes.

PMID- 19584706
TI  - Antineoplastic and cytogenetic effects of chlorpromazine on human lymphocytes in
      vitro and on Ehrlich ascites tumor cells in vivo.
AB  - The inhibitory effect of phenothiazines in tumor growth and cancer cell
      proliferation in vitro and in vivo has been established. These reports motivated
      us to investigate the genotoxic, cytotoxic, and cytostatic potential of
      chlorpromazine, alone or in combination with mitomycin C, in vitro and in vivo.
      Sister chromatid exchange levels were assessed providing a quantitative index of
      genotoxicity. In-vitro studies were performed on human lymphocyte cultures and in
      vivo studies involved Ehrilch ascites tumor (EAT) cells. An antitumour study was
      also conducted on the survival time and the ascitic volume in EAT-bearing Balb/C
      mice. The combination of chlorpromazine plus caffeine and mitomycin C exerted
      cytostatic and cytotoxic actions in human lymphocytes. The combination of
      chlorpromazine plus mitomycin C exerted cytostatic and cytotoxic actions in EAT
      cells, significantly increased the survival span of the mice inoculated with EAT
      cells, and suppressed the expected tumor growth increase. The findings of this
      basic study illustrate that high chlorpromazine concentrations increase
      chemotherapeutic effectiveness of mitomycin C. Chlorpromazine concentrations
      within the observed human plasma concentration range need to be tested along with
      antineoplastic agents in vitro for its synergistic action so as to evaluate a
      potential clinical application. Further investigation including other
      phenothiazines, biological systems, and cancer models is required.

PMID- 19584707
TI  - Hydroxychloroquine, chloroquine, and all-trans retinoic acid regulate growth,
      survival, and histone acetylation in breast cancer cells.
AB  - The antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have
      potential applications in cancer treatment. The growth of MCF-7 and MDA-MB-231
      human breast cancer cells in vitro was inhibited by CQ and HCQ and these cells
      were more sensitive than nontumorigenic MCF-10A breast epithelial cells.
      Furthermore, all-trans retinoic acid (ATRA) augmented the anticancer effects of
      CQ and HCQ as evidenced by significant reductions in Ki67-positive cancer cells
      and clonogenicity compared with cells treated with CQ or HCQ in the absence of
      ATRA. As an earlier study suggested that CQ, HCQ, and ATRA are breast cancer cell
      differentiation agents, these agents were screened in cell-free histone
      deacetylase (HDAC) and histone acetyltransferase (HAT) assays. ATRA, but not CQ
      or HCQ, inhibited HDAC activity in HeLa nuclear extracts. Growth inhibitory
      concentrations of HCQ and ATRA stimulated purified p300/CBP-associated factor,
      where CBP is the cAMP-response element binding protein, HAT activity. To
      investigate whether growth inhibitory concentrations of these agents influenced
      protein acetylation in cells, gel-purified histone H3 and histone H4 were
      analyzed using mass spectrometry. HCQ alone and HCQ+ATRA treatments altered the
      acetylation status in the N-terminal lysines of histones H3 and H4 compared with
      dimethyl sulfoxide (DMSO) controls. The results indicated that HCQ and ATRA
      regulate protein acetylation events in MCF-7 breast cancer cells, and identify a
      potential mechanism for their effects on breast cancer cell growth and
      differentiation.

PMID- 19584708
TI  - The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen
      in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells.
AB  - Tamoxifen resistance is a major clinical problem in the treatment of estrogen
      receptor alpha-positive breast tumors. It is, at present, unclear what exactly
      causes tamoxifen resistance. For decades, chlorpromazine has been used for
      treating psychotic diseases, such as schizophrenia. However, the compound is now
      also recognized as a multitargeting drug with diverse potential applications, for
      example, it has antiproliferative properties and it can reverse resistance toward
      antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug
      resistance caused by overexpression of P-glycoprotein in cancer cells. In this
      study, we have investigated the effect of chlorpromazine on tamoxifen response of
      human breast cancer cells. We found that chlorpromazine worked synergistically
      together with tamoxifen with respect to reduction of cell growth and metabolic
      activity, both in the antiestrogen-sensitive breast cancer cell line, MCF-7, and
      in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen
      sensitive and tamoxifen-resistant cells were killed equally well by combined
      treatment with chlorpromazine and tamoxifen. This synergistic effect could be
      prevented by addition of estrogen, suggesting that chlorpromazine enhances the
      effect of tamoxifen through an estrogen receptor-mediated mechanism. To
      investigate this putative mechanism, we applied biophysical techniques to simple
      model membranes in the form of unilamellar liposomes of well-defined composition
      and found that chlorpromazine interacts strongly with lipid bilayers of different
      composition leading to increased permeability. This implies that chlorpromazine
      can change influx properties of membranes hence suggesting that chlorpromazine
      may be a promising chemosensitizing compound for enhancing the cytotoxic effect
      of tamoxifen.

PMID- 19584709
TI  - Rapamycin, the mTOR kinase inhibitor, sensitizes acute myeloid leukemia cells, HL
      60 cells, to the cytotoxic effect of arabinozide cytarabine.
AB  - The mammalian target of rapamycin (mTOR) kinase is a key regulator of cell growth
      and proliferation. Overexpression of the mTOR signaling pathway has been
      described in several tumor cells, including the majority of acute myeloid
      leukemia (AML) cases. The anti-tumor efficacy of mTOR inhibitors was shown in
      several preclinical and clinical studies. In AML, however, the potential
      antineoplastic effect of mTOR inhibitors has received little attention thus far.
      In this in-vitro study of the human AML cell line, HL-60, we aimed to assess the
      antileukemic activity of rapamycin (RAPA), an mTOR inhibitor, alone and in
      combination with cytarabine (Ara-C). The study showed that RAPA in concentrations
      of 1-10 nmol/l arrested the cell cycle progression of Hl-60 cells in the G1
      phase, without evident cytotoxic effect. This effect was associated with
      significant inhibition of cyclin E expression. At concentrations higher than 10
      nmol/l, RAPA exerted a significant proapoptotic effect, with the collapse of
      mitochondrial potential and caspase-3 activation. The most prominent proapoptotic
      effect was observed for a combination of 1 nmol/l of RAPA and 50 nmol/l of Ara-C,
      especially when Ara-C was added at a 24-h interval after RAPA. In conclusion,
      these data indicate that RAPA might be effective in the treatment of acute
      leukemia patients, especially in combination with Ara-C, the drug routinely used
      in AML treatment. On the basis of these results, attempts to combine classical
      induction chemotherapy with an inhibitor of the mTOR kinase in AML treatment
      could be warranted.

PMID- 19584711
TI  - Chronic preexposure to methylphenidate cross-sensitizes methamphetamine in male
      Japanese quail.
AB  - An increasing debate exists about the potential of exposure to methylphenidate
      increasing later risk of drug abuse. The objective of this study was to
      investigate whether chronic preexposure to methylphenidate would induce cross
      sensitization to a subsequent methamphetamine challenge in male Japanese quail.
      Male quail were treated intraperitoneally with either 5, 10, or 20 mg/kg
      methylphenidate or saline for 14 days. After a 14-day washout period, birds were
      challenged with 5.6 mg/kg of methamphetamine. Methylphenidate-induced behavioral
      sensitization was not evident after 14 days of preexposure. However, locomotor
      activity was greater during the methamphetamine challenge in birds that were
      preexposed to a high dose of methylphenidate. The findings suggest that chronic
      preexposure to methylphenidate may be sufficient to alter later responding to
      methamphetamine, regardless of whether preexposure resulted in behavioral
      sensitization.

PMID- 19584710
TI  - Erythrocyte concentration distribution in sheathed microfluidic flows.
AB  - The combined effect of dissociative and associative forces on erythrocytes
      flowing in direct, layered contact with cell-free "sheath" flows in microfluidic
      systems was studied to aid in the design of blood purification devices. A blood
      stream flowed in direct contact between two fluids that were cell free. The
      layered flow created a sharp transverse concentration gradient of erythrocytes
      that promoted lateral movement of cells. This movement was perceived as both
      dispersive (arising from particle collisions or shear-enhanced movement) and
      associative (arising from rouleau formation and shear-induced migration, which
      limited the extent of movement and maintained a higher hematocrit in the central
      layer). The concentration changes of erythrocytes in the blood and sheath streams
      were measured to determine the flux of cells between streams. At flows with low
      wall shear rates, the flux of erythrocytes into the sheath streams was small.
      When shear was increased, cell flux away from the central layer increased. There
      was an intermediate shear rate that maximized cellular flux away from the center
      stream, and a further increase in shear rate showed no change in cell flux.
      Changing the transverse position of erythrocytes entering the system strongly
      affects their distribution in the exiting stream even for long fluid residence
      times. The results clarify microfluidic device design and elucidate how shear and
      hematocrit affect erythrocyte movement in blood.

PMID- 19584712
TI  - Penile erection and yawning induced by dopamine D2-like receptor agonists in
      rats: influence of strain and contribution of dopamine D2, but not D3 and D4
      receptors.
AB  - Dopamine (DA) is implicated in penile erection (PE) and yawning (YA) in rats
      through activation of D2-like receptors. However, the exact role of each subtype
      (D2, D3 and D4) of this receptor family in PE/YA is still not clearly elucidated.
      We recorded concomitantly PE and YA after treatment with agonists with various
      levels of selectivity for the different subtypes of D2-like receptors. In
      addition, we investigated the efficacy of antagonists with selective or
      preferential affinity for each of the three receptor subtypes to prevent
      apomorphine-induced PE and YA. Wistar rats were more sensitive than Long-Evans
      rats to the erectogenic activity of the nonselective DA agonist apomorphine (0.01
      0.08 mg/kg), whereas Sprague-Dawley rats were insensitive. However, all the three
      strains were equally sensitive to apomorphine-induced YA. In Wistar rats,
      apomorphine (0.01-0.63 mg/kg), the D2/D3 agonists quinelorane and (+)7-OH-DPAT
      (0.000625-10 mg/kg) or PD 128,907 (0.01-10 mg/kg), but not the D4 agonists PD
      168,077, RO-10-5824 and ABT-724 (0.04-0.63 mg/kg), produced PE and YA with bell
      shaped dose-response curves. Similarly, ABT-724 and CP226-269 (another D4
      agonist) failed to elicit PE and YA in Sprague-Dawley rats. Furthermore, in
      Wistar rats, PE and YA elicited by apomorphine (0.08 mg/kg) were not modified by
      selective D3 (S33084 and SB-277011, 0.63-10 mg/kg) or D4 (L-745,870 and RBI-257,
      0.63-2.5 mg/kg) antagonists, but were prevented by the preferential D2 blocker L
      741,626 (near-full antagonism at 2.5 mg/kg). The present data do not support a
      major implication of either DA D3 or D4 receptors in the control of PE and YA in
      rats, but indicate a preponderant role of DA D2 receptors.

PMID- 19584713
TI  - Pentoxifylline attenuates iminodipropionitrile-induced behavioral abnormalities
      in rats.
AB  - This investigation was undertaken to study the effect of pentoxifylline (PTX) on
      iminodipropionitrile (IDPN)-induced behavioral abnormalities [excitation with
      choreiform and circling movements (ECC) syndrome] in rats. The animals were
      intraperitoneally injected with IDPN (100 mg/kg) daily for 7 days. PTX was
      administered daily 30 min before IDPN in the doses of 25, 50, and 100 mg/kg for 9
      days. The animals were observed for neurobehavioral abnormalities including
      dyskinetic head movements, circling, tail hanging, air righting reflex, and
      contact inhibition of the righting reflex. The onset of ECC syndrome was observed
      on day 8 in the group treated with IDPN alone; all animals in this group became
      dyskinetic on day 10. Co-treatment with PTX dose dependently delayed the onset
      time and significantly reduced the incidence and severity of IDPN-induced ECC
      syndrome; high dose of PTX completely inhibited the abnormal behavioral signs in
      IDPN-treated rats. Administration of IDPN caused significant depletions in
      cerebral glutathione and vitamin E levels. Treatment with PTX dose dependently
      attenuated IDPN-induced oxidative stress in rats. The beneficial effects of PTX
      against IDPN toxicity may be attributed to its antioxidant and anti-inflammatory
      properties.

PMID- 19584715
TI  - Potential supplementary utility of combined PFA-100 and functional von Willebrand
      factor testing for the laboratory assessment of desmopressin and factor
      concentrate therapy in von Willebrand disease.
AB  - We performed a retrospective audit of cross-laboratory testing of desmopressin
      and factor concentrate therapy to assess the potential utility of supplementary
      testing using the PFA-100 with functional von Willebrand factor (VWF) activity
      testing. Data were evaluated for a large number of patients with von Willebrand
      disease of type 1, type 2A or type 2M, as well as a comparative subset of
      individuals with haemophilia or carriers of haemophilia. Laboratory testing
      comprised pre and postdesmopressin, or pre and postconcentrate, evaluation of
      factor VIII, VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity as
      traditionally performed, supplemented with collagen-binding (VWF:CB) testing and
      PFA-100 closure times. In brief, both therapies tended to normalize VWF test
      parameters and closure times in individuals with type 1 von Willebrand disease,
      with the level of correction in closure times related to the level of
      normalization of VWF, particularly the VWF:CB. However, although occasional
      correction of closure times was observed in patients with type 2A or type 2M von
      Willebrand disease, these did not in general normalize PFA-100 closure times
      either with desmopressin or factor concentrate therapy. In these patients,
      improvement in closure times was more likely in those in whom VWF:CB values
      normalized or when VWF:CB/VWF:Ag ratios normalized. This study confirms that
      there is a strong relationship between the presenting levels of plasma VWF and
      PFA-100 closure times, and that the supplementary combination of PFA-100 and
      VWF:CB testing might provide added clinical utility to current broadly applied
      testing strategies limited primarily to VWF:Ag, VWF ristocetin cofactor and
      factor VIII:coagulant. Future prospective investigations are warranted to
      validate these relationships and to investigate their therapeutic implications.

PMID- 19584714
TI  - Effects of environmental enrichment on sensitivity to cocaine in female rats:
      importance of control rates of behavior.
AB  - Environmental enrichment produces functional changes in mesolimbic dopamine
      transmission and alters sensitivity to psychomotor stimulants. These
      manipulations also alter the control rate of many behaviors that are sensitive to
      stimulant administration, which can make comparison of drug effects between
      isolated and enriched subjects difficult. The purpose of this study was to
      examine the effects of environmental enrichment on control rates of behavior and
      on sensitivity to cocaine in tests of locomotor activity, drug self
      administration, conditioned place preference, and toxicity. In the locomotor
      activity test, isolated rats exhibited greater activity after the administration
      of cocaine, but also had higher control rates of activity. When locomotor
      activity was expressed as a percentage of saline control values, enriched rats
      exhibited a greater increase relative to their own control than isolated rats. In
      the drug self-administration procedure, isolated rats had higher breakpoints on a
      progressive-ratio schedule of reinforcement when responding was maintained by
      cocaine; however, isolated rats also had higher breakpoints in saline
      substitution tests and higher rates of inactive lever responding. When the self
      administration data were expressed as a percentage of these control values,
      enriched rats exhibited a greater increase in responding relative to their own
      control rates than isolated rats. No differences were observed between isolated
      and enriched rats under control conditions in the place preference and toxicity
      studies. In both of these procedures, enriched rats were more sensitive than
      isolated rats to all the doses of cocaine tested. These data emphasize the
      importance of considering control rates of behavior in studies examining
      environmental enrichment and drug sensitivity, and suggest that environmental
      enrichment increases sensitivity to cocaine across a range of dependent measures
      when differences in control rates of behavior are taken into account.

PMID- 19584716
TI  - A prospective, controlled trial of a pharmacy-driven alert system to increase
      thromboprophylaxis rates in medical inpatients.
AB  - Although venous thromboembolism is an important cause of morbidity and mortality
      within the hospital, a significant proportion of at-risk inpatients do not
      receive measures known to reduce the risk of deep vein thrombosis and pulmonary
      embolism. The objective of the present study was to determine whether a pharmacy
      driven alert system would, compared to usual care, be associated with a higher
      rate of adequate venous thromboembolism prevention measures among at-risk
      inpatients on a general internal medicine service. The study was a prospective,
      controlled trial set at a university-based teaching hospital. The participants
      were adults who were admitted (Monday through Friday) to the general internal
      medicine inpatient service from 19 June to 21 September 2006. Their treatment
      included a pharmacist assessment of venous thromboembolism risk and a pharmacist
      driven alert to the treating physician. The Proportion of at-risk patients
      receiving adequate thromboprophylaxis within 36 h of admission was recorded.
      Overall, 140 patients were at sufficient risk for venous thromboembolism to be
      included. In the usual care group, prophylactic measures were ordered for 49
      (61%) of the 80 patients at moderate to high risk. In the pharmacist-alert group,
      44 (73%) of the 60 moderate to high venous thromboembolism-risk patients received
      adequate thromboprophylaxis (P = 0.15). Although we did not observe a
      statistically significant difference between the groups, our results are
      consistent with previous reports suggesting that alert systems can increase the
      proportion of hospitalized patients who receive adequate measures to prevent
      venous thromboembolism.

PMID- 19584717
TI  - Metabolomics for assessment of nutritional status.
AB  - PURPOSE OF REVIEW: The current rise in diet-related diseases continues to be one
      of the most significant health problems facing both the developed and the
      developing world. The use of metabolomics - the accurate and comprehensive
      measurement of a significant fraction of important metabolites in accessible
      biological fluids - for the assessment of nutritional status is a promising way
      forward. The basic toolset, targets and knowledge are all being developed in the
      emerging field of metabolomics, yet important knowledge and technology gaps will
      need to be addressed in order to bring such assessment to practice. RECENT
      FINDINGS: Dysregulation within the principal metabolic organs (e.g. intestine,
      adipose, skeletal muscle and liver) are at the center of a diet-disease paradigm
      that includes metabolic syndrome, type 2 diabetes and obesity. The assessment of
      both essential nutrient status and the more comprehensive systemic metabolic
      response to dietary, lifestyle and environmental influences (e.g. metabolic
      phenotype) are necessary for the evaluation of status in individuals that can
      identify the multiple targets of intervention needed to address metabolic
      disease. SUMMARY: The first proofs of principle building the knowledge to bring
      actionable metabolic diagnostics to practice through metabolomics are now
      appearing.

PMID- 19584718
TI  - Influence of Helicobacter pylori on gastric regulation of food intake.
AB  - PURPOSE OF REVIEW: To evaluate the influence of Helicobacter pylori infection on
      the gastric regulation of food intake and body weight. RECENT FINDINGS: H. pylori
      infection leads to a decrease of circulating ghrelin through a reduction of
      ghrelin-producing cells in the gastric mucosa and increases the amount of gastric
      leptin with no effect on circulating leptin levels. Eradication of H. pylori
      reverses the abnormal regulation of gastric hormone secretion. This finding is
      suggested to favor weight gain after H. pylori eradication and points to the
      potential effect of H. pylori in the pathophysiology of obesity. SUMMARY: H.
      pylori has an influence on the release of gastric hormones and therefore plays a
      role in the regulation of body weight, hunger and satiety.

PMID- 19584719
TI  - Molecular markers of aggressiveness of thyroid cancer.
AB  - PURPOSE OF REVIEW: To review recent progress at defining molecular markers that
      predict the biological behavior of thyroid cancer. RECENT FINDINGS: Thyroid
      cancer behavior is defined by the effects of the initiating oncogene as well as
      secondary events in tumor cells and the tumor microenvironment that are both
      genetic and epigenetic. Over the past several years, there has been intense focus
      on identifying molecular markers to better predict the aggressiveness of thyroid
      cancers and also to define therapeutic targets. The results of recent articles in
      this area of work are summarized with a focus of differentiated follicular-cell
      derived forms of thyroid cancer. SUMMARY: Clinical staging predicts tumor
      behavior in many cases, but does not allow true 'personalization' of initial
      therapy or identify potential therapeutic targets for patients with progressive
      disease that does not respond to standard therapies. Recent data point to several
      new opportunities to refine thyroid cancer treatment based on molecular
      information. Several highlighted articles have begun to apply this information
      with clinical intent.

PMID- 19584720
TI  - Stress and obesity: the role of the hypothalamic-pituitary-adrenal axis in
      metabolic disease.
AB  - PURPOSE OF REVIEW: Chronic stress, combined with positive energy balance, may be
      a contributor to the increased risk for obesity, especially upper body obesity,
      and other metabolic diseases. This association may be mediated by alterations in
      the hypothalamic-pituitary-adrenal (HPA) axis. In this review, we summarize the
      major research that has been conducted on the role of the HPA axis in obesity and
      metabolic disease. RECENT FINDINGS: Dysregulation in the HPA axis has been
      associated with upper body obesity, but data are inconsistent, possibly due to
      methodological differences across studies. In addition to systemic effects,
      changes in local cortisol metabolism in adipose tissue may also influence the
      risk for obesity. HPA axis dysregulation may be the causal link between
      conditions such as maternal malnutrition and sleep deprivation with metabolic
      disease. SUMMARY: The present review provides evidence for the relationship
      between chronic stress, alterations in HPA activity, and obesity. Understanding
      these associations and its interactions with other factors will be important in
      developing effective treatments for obesity and related metabolic diseases.

PMID- 19584722
TI  - Is there a role for direct renin inhibitors in chronic kidney disease?
AB  - PURPOSE OF REVIEW: To evaluate the evidence supporting the use of renin
      inhibitors to control hypertension, limit kidney disease progression, and
      decrease cardiovascular risk in patients with chronic kidney disease (CKD).
      RECENT FINDINGS: The literature on the subject is still limited. Most of the
      studies have used aliskiren as the study drug. Animal models show improved
      survival and decreased renal injury in animals receiving aliskiren. Human studies
      in patients with normal renal function show effective blood pressure control
      alone or in combination with different agents. There are no studies focusing on
      blood pressure control in patients with CKD, though the drug has been safely used
      in CKD. In a randomized clinical trial, aliskiren decreased albuminuria when
      added to losartan in patients with early diabetic nephropathy. Ongoing studies
      are evaluating the role of renin inhibitors in the prevention of cardiovascular
      events and slowing of kidney disease progression in CKD. SUMMARY: Renin
      inhibitors, specifically aliskiren, effectively decrease albuminuria. Their role
      in improving hard renal endpoints and decreasing cardiovascular events in CKD
      still remains to be established.

PMID- 19584721
TI  - The physiological impact of the serum and glucocorticoid-inducible kinase SGK1.
AB  - PURPOSE OF REVIEW: The role of serum and glucocorticoid-inducible kinase 1 (SGK1)
      in renal physiology and pathophysiology is reviewed with particular emphasis on
      recent advances. RECENT FINDINGS: The mammalian target of rapamycin complex 2 has
      been shown to phosphorylate SGK1 at Ser422 (the so-called hydrophobic motif).
      Ser397 and Ser401 are two additional SGK1-phosphorylation sites required for
      maximal SGK1 activity. A 5' variant alternate transcript of human Sgk1 has been
      identified that is widely expressed and shows improved stability, enhanced
      membrane association, and greater stimulation of epithelial Na+ transport. SGK1
      is essential for optimal processing of the epithelial sodium channel and also
      regulates the expression of the Na+-Cl- cotransporter. With regard to
      pathophysiology, SGK1 participates in the stimulation of renal tubular glucose
      transport in diabetes, the renal profibrotic effect of both angiotensin II and
      aldosterone, and in fetal programing of arterial hypertension. SUMMARY: The
      outlined recent findings advanced our understanding of the molecular regulation
      of SGK1 as well as the role of the kinase in renal physiology and the
      pathophysiology of renal disease and hypertension. Future studies using
      pharmacological inhibitors of SGK1 will reveal the utility of the kinase as a new
      therapeutic target.

PMID- 19584724
TI  - Allergic contact dermatitis in children: common allergens and treatment: a
      review.
AB  - PURPOSE OF REVIEW: The following study reviews the recent literature pertaining
      to allergic contact dermatitis (ACD) in the pediatric population. This study also
      provides an overview of the most common allergens and discusses various
      therapeutic modalities. RECENT FINDINGS: The pathophysiology of ACD is intricate
      and multifaceted, resulting in a characteristic, delayed inflammatory response.
      Although commonly recognized in adults, its existence in the pediatric population
      was questioned. Recent literature suggests that pediatric ACD exists and is more
      common than previously recognized. The diagnosis relies on the clinical
      presentation combined with appropriate use and interpretation of a patch test.
      Although many studies have investigated ACD in children, few have documented the
      relevance of positive patch test reactions until recently. The most current
      prevalence estimates of positive patch test reactions range from 14 to 70% of
      children patch tested. Although that range is broad, these studies have
      demonstrated the relevance of positive reactions and confirmed ACD as a disease
      entity in children. SUMMARY: ACD is a previously underrecognized disease process
      in the pediatric population that can manifest as a serious dermatologic challenge
      for both patients and physicians. This review will address the prevalence,
      diagnostic methods, frequent allergens and treatment options in pediatric ACD.

PMID- 19584725
TI  - Social factors and forensic psychiatry in India.
AB  - PURPOSE OF REVIEW: Forensic psychiatry is a psychiatric specialty yet to be
      recognized in many countries. This review evaluates the current status and
      practice of forensic psychiatry in India and the impact of social factors as they
      relate to this area. It evaluates existing mental health legislation, civil and
      criminal laws, the standing of teaching and training of concerned professionals
      and emphasizes the scarcity of care provisions for mentally ill prisoners. RECENT
      FINDINGS: Mental health services in India have shown a tremendous improvement,
      especially during the last two decades. However there are some isolated reports
      of people with mental health disorders having been exposed to a wide range of
      human rights violations. Several reports identified gross inadequacies in the
      current mental health legislation and judicial apathy. SUMMARY: Forensic
      psychiatry in India at the dawn of the 21st century is practised in an
      environment of a bewildering mosaic of scarce resources, conflicting interests
      and apparent apathy of government, policy makers and legislators. Human rights
      and privileges to live with dignity of mentally ill prisoners have not been given
      adequate attention until now. This study also identifies pertinent issues for the
      future development of forensic psychiatry in India.

PMID- 19584726
TI  - Legal controls of the medical profession.
AB  - PURPOSE OF REVIEW: The authors, after a brief historical review of the theme,
      review the articles published in the last year. The purpose is to verify how the
      field has moved on during this period, as a constant increase of legal and social
      controls on the medical profession is perceived. RECENT FINDINGS: Surprisingly,
      very few articles treating directly the theme reviewed were found. The better
      part of the articles examined legal aspects of the medical profession in a
      nonsystematic way. Among the ones selected those that dealt with internal
      controls (produced by the professional categories such as the Clinical Practice
      Guidelines) and those that dealt with external controls (produced by other social
      groups) could be identified. SUMMARY: The authors conclude that the existence of
      limits and internal and external controls is fundamental for a professional
      medical practice of quality. However, the excess of controls, which causes a
      defensive attitude, may negatively interfere in the quality of the care offered
      to patients.

PMID- 19584723
TI  - Clinical research directions in pediatric cardiology.
AB  - PURPOSE OF REVIEW: Clinical research in pediatric cardiology is under-appreciated
      and under-funded, yet it has enormous implications for cardiovascular health and
      healthcare over the entire life-course. Renewed interest in federally funded
      clinical research makes it timely to propose a comprehensive research agenda
      that, with its associated rationale, will attract public funds for research into
      child cardiovascular health and disease. RECENT FINDINGS: We propose here a
      comprehensive pediatric cardiology research agenda consisting of 22 topics and
      associated research questions. We describe the following five topics in more
      detail: the need for life-course studies of pediatric cardiac disease and
      epigenetic factors for later onset of cardiovascular effects; the need to study
      cardiometabolic disease risk in children; recent pediatric cardiology clinical
      trials and observational studies; the need to explore the role of physical
      activity in preventing and treating pediatric cardiology patients; and the need
      to develop and implement evidence-based interventions to manage pediatric
      cardiovascular problems. SUMMARY: If the field of pediatric cardiology can adopt
      a comprehensive research agenda that identifies the most-needed studies, then
      research could be better coordinated, long-term and collaborative studies would
      be more readily organized and funded, and the overall financial and scientific
      efficiency of research in pediatric cardiology would be improved. Targeted
      research efforts are more likely to realize potential breakthroughs in areas such
      as genetic and epigenetic screening, biomarkers, cardioprotective strategies,
      life-course studies, long-term monitoring technologies, environmental influences
      on disease, evidence-based practice guidelines, and more rapid and safer
      development of drugs.

PMID- 19584727
TI  - Prevention of complete heart block in children of mothers with anti-SSA/Ro and
      anti-SSB/La autoantibodies: detection and treatment of first-degree
      atrioventricular block.
AB  - PURPOSE OF REVIEW: To describe the results of two recent prospective studies that
      may indicate how to monitor, diagnose, and treat fetuses with neonatal lupus
      manifesting with heart involvement and to summarize additional research reports
      regarding the pathophysiology and outcomes of this rare condition. RECENT
      FINDINGS: The PR Interval and Dexamethasone Evaluation study found 10 cases of
      neonatal lupus (10%) with three first-degree atrioventricular blocks (AVBs) and
      three complete heart blocks. The study included 98 pregnancies in 95 women with
      anti-SSA/Ro antibodies who completed weekly fetal Doppler echocardiogram-based
      evaluation. The authors concluded that they were unable to detect first-degree
      AVB before progression to complete heart block. A similar observational
      prospective study was performed in 70 fetuses of 56 mothers using tissue velocity
      fetal kinetocardiogram for measurement of PR prolongation. In this study, six
      fetuses (8.5%) showed first-degree AVB, and fast normalization of heart function
      was achieved through maternal treatment with fluorinated steroids. The authors
      concluded that fetal kinetocardiogram can detect first-degree AVB in the fetus
      exposed to maternal anti-SSA/Ro or anti-SSB/La antibodies or both and that
      fluorinated steroids given on detection were associated with normalized
      atrioventricular conduction in fetuses with first-degree AVB. SUMMARY: Echo
      Doppler seems a less reliable method for early detection of fetus first-degree
      AVB, and it is suggested that fetal kinetocardiogram or fetal electrocardiography
      are preferred. Although atrioventricular block reverses spontaneously in some
      fetuses, parents and treating physicians should consider immediate treatment with
      fluorinated steroids once a first-degree AVB is detected due to the high risk of
      rapid progression to complete blockage.

PMID- 19584728
TI  - Statistical approaches to evaluating the effect of risk factors on the pain of
      knee osteoarthritis in longitudinal studies.
AB  - PURPOSE OF REVIEW: We describe commonly used measures of knee pain in
      longitudinal studies and review various analytic approaches to evaluating the
      effect of a risk factor on each type of pain measure. RECENT FINDINGS: In
      longitudinal epidemiologic studies of knee pain, frequent knee pain and activity
      related pain severity are the most commonly used measures for pain. Various
      analytic approaches have been used to evaluate the effect of a risk factor on
      each type of pain measure. Analytic approaches utilized include the generalized
      estimating equations model and the mixed-effects linear regression model for pain
      severity assessed as a continuous outcome variable, the mixed-effects logistic
      regression model and conditional logistic regression model for pain exacerbation
      measured as a dichotomous outcome variable, and a mixed-effects regression model,
      stratified proportional odds model, and a multistate transition model for pain
      severity measured as an ordinal outcome variable. SUMMARY: Compared with cross
      sectional studies, longitudinal studies allow investigators to assess the effect
      of change in a risk factor of interest on change in risk of knee pain or change
      in pain severity. With appropriate analysis methods, investigators are able to
      minimize potential confounders that differ among individuals or knees but which
      do not vary over time within a person or knee.

PMID- 19584729
TI  - Pathogenesis of kidney disease in systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: A combination of systemic autoimmunity and tissue response to
      immune injury underlie renal involvement in lupus erythematosus. In this review,
      we discuss recent literature investigating pathogenetic mechanisms of lupus
      glomerulonephritis. RECENT FINDINGS: In lupus glomerulonephritis, glomerular
      immune complexes were believed to be the primary mediators of renal disease.
      Recent studies make it apparent that autoantibodies of multiple specificities
      participate in the formation of immune complexes, deposited in the kidneys. Renal
      infiltration by T cells, macrophages, and dendritic cells have a dominant role in
      the progression of lupus glomerulonephritis leading to renal failure. Activation
      of Toll-like receptors modulates autoantibody production and systemic interferon
      responses. However, glomerular cell responses to immune injury influence disease
      outcome. In addition, new insights on the genetics of susceptibility to end-organ
      damage in lupus glomerulonephritis have been discovered. Differential glomerular
      responses reflected in gene expression profiles during disease progression
      provide potential markers for diagnosis of lupus glomerulonephritis progression
      and flares. In addition, studies of end-organ responses provide new targets for
      therapeutic interventions. SUMMARY: Lupus glomerulonephritis is a prototype of
      immune complex disease mediated by autoantibodies of multiple specificities, one
      of which is anti-DNA. Murine models of spontaneous systemic lupus erythematosus
      have been critical for understanding the underlying disease. Recent studies
      demonstrate that in addition to systemic autoimmunity, end-organ responses, and
      end-organ resistance to damage are also critical in determining disease outcome.
      This understanding should influence design of novel therapeutic approaches in
      systemic lupus erythematosus.

PMID- 19584731
TI  - Hereditary and familial kidney cancer.
AB  - PURPOSE OF REVIEW: Changing strategies in the evaluation and treatment of renal
      neoplasms have been fostered by developments in the understanding of the genetics
      and molecular biology of renal tumors. Many of these discoveries have come from
      research into hereditary kidney cancer syndromes and the genetic mutations
      responsible for tumorigenesis. The purpose of this review is to familiarize the
      reader with the known heritable forms of kidney cancer, the recent advances in
      the field and their impact on patient management. RECENT FINDINGS: Genetic and
      phenotypic characterization of renal cancer syndromes includes von Hippel-Lindau
      disease, Birt-Hogg-Dube syndrome, hereditary papillary renal carcinoma, and
      hereditary leiomyomatosis and renal carcinoma. SUMMARY: Hereditary kidney cancer
      syndromes offer valuable insight into the pathogenesis of kidney cancer through
      identification of the underlying genetic mechanisms common to hereditary and
      sporadic forms of disease. An understanding of the manifestations of these
      diseases is necessary to allow for accurate diagnosis of patients and to provide
      the opportunity for appropriate screening. Conservative management strategies
      have been developed and should be followed to limit treatment-related morbidity.

PMID- 19584730
TI  - Emerging new pathways of pathogenesis and targets for treatment in systemic lupus
      erythematosus and Sjogren's syndrome.
AB  - PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) and Sjogren's syndrome are
      chronic inflammatory diseases characterized by the dysfunction of T cells, B
      cells, and dendritic cells and the production of antinuclear autoantibodies.
      Here, we evaluate newly discovered molecular and cellular targets for the
      treatment of SLE and Sjogren's syndrome. RECENT FINDINGS: The mammalian target of
      rapamycin in T and B cells has been successfully targeted for treatment of SLE
      with rapamycin or sirolimus both in patients and animal models. Inhibition of
      oxidative stress, nitric oxide production, interferon alpha, toll-like receptors
      7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function,
      lysosome function, endosome recycling, and the nuclear factor kappa B pathway
      showed efficacy in animal models of lupus. B-cell depletion and blockade of anti
      DNA antibodies and T-B cell interaction have shown success in animal models,
      whereas human studies have so far failed to accomplish clinical endpoints,
      possibly due to inadequacies in study design. SUMMARY: Discovery of novel genes
      and signaling pathways in lupus pathogenesis offers novel biomarker-targeted
      approaches for treatment of SLE and Sjogren's syndrome.

PMID- 19584732
TI  - Biomarkers in renal cell carcinoma.
AB  - PURPOSE OF REVIEW: To review the latest information on biomarkers in renal cell
      carcinoma and their use in integrated staging systems. RECENT FINDINGS: The
      discovery of the Von Hippel-Lindau defect and the hypoxia inducible factor-1alpha
      transcripted genes has led to an explosion in the understanding of molecular
      pathways in renal cell carcinoma. The two most prominent biomarkers are carbonic
      anhydrase IX and vascular endothelial-derived growth factor. Carbonic anhydrase
      IX has demonstrated excellent specificity and ability to predict treatment
      response. Vascular-derived growth factor has good correlation with stage, grade
      and increased levels with adverse survival. Markers such as CXCL16, ADAM10, B7
      H1, Ki-67, survivin, P53, GLUT-1, calveolin-1 and endoglin are continuously being
      validated. CXCL16 is one of the newest biomarkers, is significantly expressed in
      papillary renal cell carcinoma and is an independent prognostic marker for better
      patient survival. The incorporation of biomarkers into integrated staging systems
      such as UCLA Integrated Staging System, SSIGN and Bioscore are discussed and
      compared. SUMMARY: The use of novel molecular biomarkers are being incorporated
      into clinical practice. The understanding of molecular pathways will lead to
      tailored treatment to the individual patient.

PMID- 19584733
TI  - Surgery for vena caval tumor extension in renal cancer.
AB  - PURPOSE OF REVIEW: We review recent efforts designed to improve the preoperative
      assessment, minimize the surgical morbidity, and develop multimodal treatments
      for patient with renal cell carcinoma and venous tumor thrombus. RECENT FINDINGS:
      The ability of computerized tomography to classify venous thrombus has improved
      with recent advancements in multidetector/three-dimensional technology. The
      utility of preoperative imaging to predict vascular wall invasion, which carries
      adverse prognostic significance, has also been demonstrated. Minimally invasive
      approaches to low-level thrombus cases have been explored, whereas techniques to
      minimize the morbidity associated with the use of cardiopulmonary bypass and
      circulatory arrest in patients with a retrohepatic or supradiaphragmatic
      thrombus, including antegrade cerebral perfusion, the use of cardiopulmonary
      bypass with mild hypothermia, and the increased application of veno-venous
      bypass, have improved perioperative outcomes. Meanwhile, results from several
      case reports suggest a potential role for neoadjuvant systemic therapy with
      tyrosine kinase inhibitors prior to resection. SUMMARY: Improvements in
      perioperative assessment and surgical technique have decreased the morbidity and
      improved the outcomes for patients with renal cell carcinoma and venous tumor
      thrombus. Further investigations of the role for targeted therapies in the
      management of these complex patients are needed to define the optimal multimodal
      approach.

PMID- 19584734
TI  - Potential new urinary markers in the early detection of bladder cancer.
AB  - PURPOSE OF REVIEW: Bladder cancer remains a highly prevalent and lethal
      malignancy. Early diagnosis and prompt treatment have been shown to improve
      survival at both initial diagnosis and recurrence. A vast number of tumor markers
      have been identified and rigorously evaluated in attempts to improve noninvasive
      diagnostic accuracy of bladder cancer. Hematuria was the first tumor marker in a
      field that has grown to include soluble markers, cell-surface antigens, cell
      cycle-related proteins, and genetic alterations. We aim to provide a critical
      appraisal of newer markers and the current state of research. RECENT FINDINGS:
      The number of tumor markers identified has been exponentially increasing. For a
      variety of reasons, many are unsuitable for clinical practice. More promising
      recent markers include those discovered in the fields of genomics, proteomics,
      and epigenetics. Much of the recent work is focused on molecular genetic pathways
      in bladder cancer. SUMMARY: The field of bladder cancer tumor markers remains a
      rapidly evolving area in which newer markers are constantly identified,
      evaluated, and often discarded if they do not add significantly to the
      urologists' armamentarium. Newer markers rely on genetic rearrangements,
      molecular changes, and cell-cycle-related proteins. Work is currently being done
      to identify the most promising markers.

PMID- 19584735
TI  - Physical activity levels among urban and rural women in south India and the risk
      of breast cancer: a case-control study.
AB  - Breast cancer (BC) incidence in India is approximately 100% higher among urban
      women than rural women. The role of household activities (HA) among urban and
      rural women in the development of BC was investigated. The study was conducted
      between 2002 and 2005, at the Regional Cancer Center, Trivandrum and three cancer
      hospitals in Chennai. Cases (735 urban and 1131 rural) were women with
      histologically confirmed incident BC. Controls (631 urban and 1242 rural) were
      age-matched women, who accompanied cancer patients to the hospital. Using in
      person interview, information on time spent on HA and potential confounding
      variables was collected. Odds ratio (OR) and 95% confidence intervals (CI) of BC
      were estimated according to the time spent on HA through logistic regression
      models. Time spent on HA was longer among rural women (urban vs. rural: 48 vs.
      59% in Trivandrum and 31 vs. 41% in Chennai for 5 or more hours/day on HA). The
      risk of BC declined with increasing time spent on HA. Compared with less than 3
      h/day, the ORs for 5-6 h/day were 0.48 (95% CI: 0.32-0.72) in premenopausal and
      0.49 (95% CI: 0.34-0.72) in postmenopausal women. Corresponding ORs for 6 or more
      hours/day were 0.70 (95% CI: 0.48-1.02) and 0.51 (95% CI: 0.35-0.73). The study
      supports the hypothesis that a high level of physical activity (PA) contributes
      to the difference in BC risk between urban and rural women in India. The
      proportion of BC avoided because of moderate or high PA was estimated to be 19%
      in urban women and 38% in rural women.

PMID- 19584736
TI  - The impact of analgesia on the diagnostic accuracy of the sonographic Murphy's
      sign.
AB  - OBJECTIVES: Administering analgesia to patients with abdominal pain before
      diagnostic imaging is now accepted as standard practice. However, analgesia
      before diagnostic right upper quadrant ultrasound continues to be controversial
      for fear of masking the sonographic Murphy's sign (SMS). This study sought to
      evaluate the impact of analgesia on the accuracy of the SMS in predicting
      cholecystitis. We hypothesized that the impact of analgesia on radiologist
      performed ultrasound and emergency physician (EP)-performed ultrasound would be
      equivalent. METHODS: Thirty patients presenting to the emergency department with
      abdominal pain were randomized to receive placebo or meperidine for the first two
      doses of medication. The patients underwent EP performed right upper quadrant
      ultrasound before and after the administration of medication, in addition to
      receiving a radiology department ultrasound postmedication. The presence of SMS
      was then compared with final hospital or pathological diagnosis. RESULTS: Eleven
      of 30 patients (37%) had a final diagnosis of cholecystitis and only one patient
      had a change in their SMS postmedication. The EP assessment for postmedication
      SMS had a sensitivity of 0.82 [confidence interval (CI): 0.48-0.97] and
      specificity of 0.95 (CI: 0.71-0.99) for cholecystitis. The radiology assessment
      for postmedication SMS had a sensitivity of 0.17 (CI: 0.01-0.63) and specificity
      of 1 (CI: 0.74-1) for cholecystitis. CONCLUSION: This pilot study shows that
      analgesia does not significantly change the assessment of SMS when performed by
      an EP sonographer. It also suggests that EP-performed ultrasound may be more
      accurate in assessing this predictive sign of cholecystitis.

PMID- 19584737
TI  - Emergency department presentations with suspected acute coronary syndrome-
      frequency of self-reported cocaine use.
AB  - The objective of this study was to assess the prevalence of self-reported cocaine
      use in individuals presenting to the Emergency Department (ED) with suspected
      myocardial ischaemia/acute coronary syndrome (ACS). A retrospective review (1
      January to 31 December 2008) of all suspected myocardial ischaemia/ACS
      presentations to our ED was undertaken. Basic demographic data and use/nonuse of
      cocaine were recorded from notes; where appropriate the route of use, concomitant
      use of other recreational drugs/ethanol, presenting features and treatment(s)
      were extracted. Self-reported cocaine use was recorded in 54 (1.9%) of the 2810
      presentations. The mean+/-SD age of those who self-reported the use of cocaine
      (28.9+/-9.0) was significantly lower than those who did not (52.3+/-12.7)
      (P<0.0001). Twenty (37.0%) of those with cocaine use had one or more features of
      potential cocaine (sympathomimetic) toxicity at presentation to the ED. In
      conclusion, self-reported recent cocaine use was documented in a clinically
      significant minority of patients with suspected myocardial ischaemia/ACS.

PMID- 19584738
TI  - The response to hepatitis B vaccine: does it differ in celiac disease?
AB  - OBJECTIVES: There is a relationship between nonresponsiveness to hepatitis B
      virus (HBV) vaccine and certain human leukocyte antigen (HLA) genotypes. In
      healthy population, 4-10% vaccine recipients fail to produce protective levels of
      antibodies to the HBV vaccine after standard immunization depending upon age and
      the presence of various underlying diseases. Celiac disease (CD) is an HLA
      associated immunological disease. It has been suggested that certain HLA
      haplotypes which are linked to CD are associated with nonresponse to HBV vaccine
      as well. The aim of this study is to assess the response to HBV vaccine
      prospectively in a group of CD and to explore the potential link between CD and
      HBV vaccine nonresponse by studying shared HLA haplotypes. PATIENTS AND METHODS:
      Sixty-three previously diagnosed celiac patients who were on a strict gluten-free
      diet (GFD) and 54 healthy children were evaluated serologically for anti-HBs
      status. Celiac children who were anti-HBs negative at baseline were fully
      vaccinated prospectively, and reevaluated for the response to HBV vaccine. To
      estimate the role of HLA type in HBV vaccine response in celiac patients, a
      subgroup of both patients and control participants had HLA genotypes performed.
      RESULTS: At enrollment, 27 (67.5%) children with CD and 48 (85.2%) healthy
      children were anti-HBs positive, and the difference between patients and controls
      was statistically significant (P<0.05). However, failure to respond to HBV
      vaccine was only 3.6% (response rate 96.4%) in prospectively vaccinated celiac
      patients. There was no relationship between HLA type and vaccine nonresponse in
      our study group. CONCLUSION: The response to HBV vaccine in celiac children who
      were compliant to GFD is not different from a healthy population. CD may be one
      of the immune diseases associated with a high rate of HBV vaccine nonresponse but
      it might not be permanent and treatment with GFD and compliance to the treatment
      may ameliorate the immune response to HBV vaccine in celiac children.

PMID- 19584739
TI  - The effect of prolonged-release melatonin on sleep measures and psychomotor
      performance in elderly patients with insomnia.
AB  - Objectives of this study were to investigate the effects of prolonged-release
      melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in
      patients aged > or =55 years with primary insomnia, as defined by fourth revision
      of the Diagnostic and Statistical Manual of Mental Disorders of the American
      Psychiatric Association. Patients (N = 40) were treated nightly single-blind with
      placebo (2 weeks), randomized double-blind to PRM or placebo (3 weeks) followed
      by withdrawal period (3 weeks). Sleep was assessed by polysomnography, all-night
      sleep electroencephalography spectral analysis and questionnaires. Psychomotor
      performance was assessed by the Leeds Psychomotor Test battery. By the end of the
      double-blind treatment, the PRM group had significantly shorter sleep onset
      latency (9 min; P = 0.02) compared with the placebo group and scored
      significantly better in the Critical Flicker Fusion Test (P = 0.008) without
      negatively affecting sleep structure and architecture. Half of the patients
      reported substantial improvement in sleep quality at home with PRM compared with
      15% with placebo (P = 0.018). No rebound effects were observed during withdrawal.
      In conclusion, nightly treatment with PRM effectively induced sleep and improved
      perceived quality of sleep in patients with primary insomnia aged > or =55 years.
      Daytime psychomotor performance was not impaired and was consistently better with
      PRM compared with placebo. PRM was well tolerated with no evidence of rebound
      effects.

PMID- 19584740
TI  - Proliferation, but not interleukin 2 production, of Gag-specific CD8+ T cells is
      associated with low HIV viremia and high CD4 counts in HIV-1-infected Chinese
      individuals.
AB  - BACKGROUND: To control HIV globally, a comprehensive understanding of host
      immunity to HIV in different human populations is needed. Relatively, little is
      known on the quantity and quality of HIV-specific T-cell responses in Chinese
      patients. METHODS: We quantified HIV Gag-specific CD8+ and CD4+ T cells that are
      capable of producing interferon (IFN)-gamma and interleukin 2 and assessed their
      proliferative capacity in a cohort of 53 antiretroviral-naive chronically HIV-1
      infected Chinese patients. RESULTS: The proliferation of Gag-specific CD8+ T
      cells, but not their IFN-gamma or interleukin 2 production, was inversely
      proportional to HIV viral load and directly proportional to CD4+ T-cell counts.
      Gag-specific CD8+ T-cell proliferation was proportionate to the frequency of IFN
      gamma-secreting CD8+ T cells. Such correlations, however, did not exist for Gag
      specific CD4 T cells. CONCLUSIONS: These results suggest that good quality and
      large quantities of HIV Gag-specific T-cell responses are associated with
      virologic control in HIV-1-infected Chinese patients. We infer that protective T
      cell vaccines tested in other populations should also provide benefit to the
      Chinese population.

PMID- 19584742
TI  - Sudden death in a patient with idiopathic right ventricular outflow tract
      arrhythmia.
AB  - Idiopathic ventricular tachycardia originating from the right ventricular outflow
      tract (RVOT) and idiopathic RVOT extrasystoles are generally considered benign
      arrhythmias. We describe the case of a patient with typical RVOT arrhythmias
      without any symptoms for many years, who died suddenly the day before a planned
      electrophysiological study. The only disquieting signs in her clinical history
      were a relatively short coupling interval of premature ventricular contractions
      in some ECG recordings and an isolated run of polymorphic nonsustained
      ventricular tachycardia induced by an RVOT extrasystole during previous ECG
      monitoring.

PMID- 19584741
TI  - Using social networks to recruit an HIV vaccine preparedness cohort.
AB  - OBJECTIVES: To evaluate a social network approach to develop an adolescent cohort
      for HIV vaccine preparedness and investigate characteristics that influence
      recruitment. METHODS: We summarize baseline data from a prospective cohort study
      that included 4 sessions over 6 months. Fifty-nine HIV-infected adolescent and
      adult patients of a family-based HIV clinic named significant others and
      indicated willingness to involve them in this study. Sixty-two adolescent and
      adult significant others not known to be HIV infected were enrolled. Logistic
      regression was used to estimate factors associated with willingness. RESULTS:
      Participants identified 624 social network members including 276 adolescents
      (44%). Network member's awareness of the index's HIV positivity (P < 0.01) and
      older age (P = 0.05) affected willingness. Respondents were less willing to
      invite drug-risk alters (P = 0.006). Adolescents were willing to invite more
      adolescents than were adults (P < 0.0001). Adolescents younger than 18 years old
      reported fewer sexual and drug-using risk behaviors than expected. CONCLUSIONS:
      HIV-infected patients are willing to recruit their social networks, provided
      concerns about disclosure of HIV status are addressed. Using social networks to
      identify and recruit adolescent populations is appropriate and feasible for
      vaccine preparedness activities, future vaccine trials, and other prevention
      programs, but procedures are needed to selectively identify and retain high-risk
      youth.

PMID- 19584743
TI  - Capecitabine-induced cardiotoxicity: when to suspect? How to manage? A case
      report.
AB  - We present a case of capecitabine-induced cardiac toxicity manifested by chest
      pain, ST-segment elevation and ventricular tachycardia. Symptoms and ECG
      alterations were completely reversible after withdrawal of the drug. Coronary
      angiography demonstrated the absence of epicardial coronary spasm. We suggest
      cardiac monitoring with ECG Holter and effort ECG during the first days of drug
      administration. Prompt evaluation of chest pain in this setting is of paramount
      importance.

PMID- 19584744
TI  - Myocardial scarring following chemotherapy for multiple myeloma detected using
      late gadolinium hyperenhancement cardiovascular magnetic resonance.
AB  - We present the case of a 60-year-old lady who was treated with chemotherapy for
      myeloma. Following initiation of bortezomib, she developed heart failure which
      was associated with a reduction in left ventricular systolic function. A
      gadolinium enhanced cardiovascular magnetic resonance scan demonstrated midwall
      hyperenhancement consistent with midwall fibrosis.

PMID- 19584745
TI  - Toxic agents in a toxic research environment? The case of contrast ultrasound.

PMID- 19584746
TI  - How long does it take to make an accurate diagnosis in an epilepsy monitoring
      unit?
AB  - This study reports the existence of patients requiring prolonged monitoring with
      video-electroencephalography to make an accurate diagnosis and to quantify how
      often this occurs. The authors performed a retrospective review of 248
      consecutive adult patients admitted to the epilepsy monitoring unit during 12
      months for event characterization or presurgical evaluation. For the diagnosis of
      definite epilepsy, at least one epileptic seizure must have been recorded with
      video-electroencephalography. The median time to first diagnostic event, whether
      epileptic seizure or nonepileptic event, was 2 days; 35% required 3 or more days
      and 7% >1 week. Twelve percent of those with definite epilepsy never had
      interictal epileptiform discharges and 17% of those with nonepileptic events had
      interictal epileptiform discharges. Six percent of patients with definite
      epilepsy had neither epileptic seizures nor interictal epileptiform discharges
      until day 3 or after. Based on our results, it is common to require 3 or more
      days in an epilepsy monitoring unit to record and diagnose the nature of
      paroxysmal episodes and not rare to require more than a week. Interictal
      electroencephalography alone cannot reliably distinguish between those with
      epileptic seizures and nonepileptic events.

PMID- 19584747
TI  - Relationships between sleep spindles and activities of the cerebral cortex after
      hemispheric stroke as determined by simultaneous EEG and MEG recordings.
AB  - This study aimed to determine the relationships between the amplitude and
      cortical-activating areas in each hemisphere for 14-Hz centro-parietal spindles
      to clarify the involvement of the cortex in the asymmetry of spindles after
      hemispheric stroke with putaminal or thalamic hemorrhage using simultaneous
      recording of the electroencephalogram and magnetoencephalogram. Spontaneous
      cortical activities during sleep stage 2 (spindles) were simultaneously recorded
      from 10 patients with putaminal or thalamic hemorrhage with a 60-channel
      electroencephalogram and a 306-channel whole-head magnetoencephalogram. Based on
      the frequencies and cortical distributions recorded with electroencephalogram,
      the 14-Hz centro-parietal and 12-Hz frontal spindles were differentiated. The
      cortical sources of the 14-Hz centro-parietal spindles were identified with
      magnetoencephalogram as equivalent current dipoles. Activation centered in four
      areas, the pre- and postcentral areas in posterior frontal cortex and parietal
      cortex of each hemisphere. However, these areas were not always activated
      simultaneously. Reduction of amplitude in the affected hemisphere after
      hemispheric stroke indicated reduction of areas of activation or activation
      strengths in the ipsilateral hemisphere. For some spindles, when reduction of
      amplitude of above 50% occurred in the affected hemisphere compared with the
      nonaffected hemisphere, no activation occurred in the ipsilateral hemisphere.
      Reduction of amplitude was related to the reduction of areas of cortical
      activation and activation strengths. Reduction of amplitude also occurred over
      the nonaffected hemisphere, and reduction of cortical activating area and
      activation occurred in the nonaffected hemisphere, suggesting that the cerebral
      hemispheres are involved in the eneration of spontaneous sleep spindles. The
      stronger ipsilateral effects of cerebral lesions on spindle oscillations
      indicated reduction of amplitude of sleep spindles in the ipsilateral hemisphere,
      as well as reduction of cortical activation of spindle oscillations and
      underlying corticothalamic projections. Simultaneous electroencephalogram and
      magnetoencephalogram recordings can yield valuable findings concerning the
      functional asymmetry between hemispheres after hemispheric stroke from the
      relationships between the amplitude and patterns of cortical activation
      associated with spindles.

PMID- 19584748
TI  - The effects of transcranial stimulation on paretic lower limb motor excitability
      during walking.
AB  - Balanced transcallosal inhibition sustains symmetrical corticomotor excitability
      and assists the performance of bimanual voluntary movements. After stroke,
      transcallosal inhibition becomes asymmetric. This finding raised the notion that
      reducing poststroke asymmetry in transcallosal inhibition might prime the motor
      system before training and lead to improvements in walking recovery. In this
      study, we examined three neuromodulatory protocols applied during walking to
      determine if they could increase ipsilesional and decrease contralesional motor
      excitability in patients with chronic stroke. Inhibitory repetitive transcranial
      magnetic stimulation and inhibitory paired associative stimulation were applied
      to the contralesional motor system, and facilitatory anodal transcranial direct
      current stimulation was applied to the ipsilesional motor system. We tested the
      bilateral modulatory effects of each stimulation protocol on the tibialis
      anterior, medial gastrocnemius, medial hamstrings, and vastus lateralis of nine
      patients with chronic stroke. All stimulation protocols increased paretic limb
      and decreased nonparetic limb motor excitability. There was no statistical
      difference in the extent of modulation between these stimulation protocols. This
      result suggests these three protocols are promising candidate priming mechanisms
      for testing the hypothesis in a future study that reducing the poststroke
      asymmetry of between-hemisphere motor excitability will enhance the effect of
      gait therapy.

PMID- 19584749
TI  - Imaging compatible electrodes for continuous electroencephalogram monitoring in
      the intensive care unit.
AB  - Continuous electroencephalogram in the intensive care unit is increasingly
      recognized as an important diagnostic and prognostic tool in critically ill
      patients. Metal disc electrodes or subdermal needle electrodes are neither
      computed tomography nor magnetic resonance imaging compatible. Their frequent
      replacement required for imaging purposes is time consuming and contributes to
      scalp breakdown. We have developed and report on two new types of imaging
      compatible electrodes. The subdermal wire electrode and the silver-epoxy-coated
      conductive plastic electrode are magnetic resonance imaging, computed tomography,
      and angiogram compatible. Moreover, the subdermal wire electrode does not require
      any daily maintenance. The electrodes were used on a total of 24 intensive care
      unit patients (subdermal wire electrode = 20, conductive plastic electrodes = 4)
      who required continuous electroencephalogram. During an average of 62.2 +/- 44
      hours of electroencephalogram recording, 54% of the patients underwent imaging
      procedures (nine magnetic resonance imagings, five computed tomographic scans,
      and two angiograms) of good quality without the need to remove/replace the
      electrodes. The continuous electroencephalogram revealed epileptogenic activity
      that was not detected on standard 20-minute recordings in 28% of patients
      screened, with electrographic seizures in 11%. These two types of imaging
      compatible electrodes offer definite advantages in clinical practice. The
      combined diagnostic information of continuous electroencephalogram and easy-to
      plan imaging yields important results and improves the clinical management and
      treatment of intensive care unit patients.

PMID- 19584750
TI  - Inverse modeling on decomposed electroencephalographic data: a way forward?
AB  - Inverse modeling is typically applied to instantaneous electroencephalogram
      signals. However, this approach has several shortcomings including its
      instability to model multiple and deep located dipole sources and the
      interference of background noise may hamper the sensitivity, stability, and
      precision of the estimated dipoles. This article validates different dipole
      estimation techniques to find the most optimal combination of different analysis
      principles using both simulations and recordings. Electroencephalogram data were
      simulated with six known source locations. First, a dataset was simulated with
      sources chosen to mimic somatosensory-evoked potentials to electrical stimuli.
      Additionally, 20 further datasets were simulated each containing six randomly
      located and oriented sources. The simulated sources included superficial, deep,
      and simultaneously active sources. Furthermore, somatosensory-evoked potentials
      to median nerve stimuli were recorded from one subject. On both simulated and
      recorded evoked potential data, three different methods of signal decomposition
      were compared: independent component analysis (ICA), second-order blind
      identification (SOBI), and multichannel matching pursuit (MMP). For inverse
      modeling of the brain sources, the DIPFIT function of the EEGLAB software was
      used on raw and decomposed data. MMP was able to separate all simulated
      components that corresponded to superficial, deep, and simultaneously active
      sources. ICA and SOBI were only able to find components that corresponded to
      superficial sources. For the 20 randomized simulations, the results from the
      evoked potential simulation were reproduced. Inverse modeling on MMP components
      (atoms) was better than on ICA or SOBI components (P < 0.001). DIPFIT on MMP
      atoms localized 99.2% of the simulated dipoles in correct areas with their
      correct time/frequency distribution. DIPFIT on ICA and SOBI components localized
      35% and 39.6%, respectively of the simulated dipoles in correct areas. As for the
      real-evoked potentials recorded in one subject, DIPFIT on MMP atoms allowed us to
      build a dipole model closer to the current physiological knowledge than dipole
      modeling of ICA and SOBI components. The results show that using MMP before
      inverse modeling is a reliable way to noninvasively estimate cortical activation.

PMID- 19584751
TI  - Sleep structure in patients with periodic limb movements and obstructive sleep
      apnea syndrome.
AB  - Periodic limb movements (PLM) and obstructive sleep apnea syndrome (OSAS) are two
      frequent sleep disorders which often occur in the same patient. The goal of this
      study was to know the influence of the presence of PLM in the sleep architecture
      in patients with and without OSAS. Two hundred twenty consecutive patients (69
      women and 151 men) participated in this transversal study. They were patients
      with clinical suspicion of dysomnia, including snoring, OSAS, and PLM. All of
      them underwent a full polysomnography and were interviewed using questionnaires
      about the sleep quality. The sleep parameters (percentage of sleep stages, rapid
      eye movement latency, sleep efficiency, awakenings, PLM presence, apnea-hypopnea
      index) were calculated and compared between groups. Descriptive statistics and
      nonparametric distribution techniques were used for the analysis. Patients with
      PLM when compared with patients with OSAS had lower sleep efficiency and less
      rapid eye movement percentage. The presence of PLM in patients with sleep apnea
      was less relevant being responsible only for an increase in the rapid eye
      movement latency and a decrease in the duration of the three to four sleep
      stages. However, the presence of OSAS was related to a better sleep efficiency
      (patients with PLM plus OSAS had a better sleep efficiency than patients with
      only PLM). PLM alters the structure of sleep. In patients with sleep apnea, the
      presence of PLM is less relevant.

PMID- 19584752
TI  - Simple renal cysts and arterial hypertension: does their evacuation decrease the
      blood pressure?
AB  - OBJECTIVE: To evaluate the relationships between simple renal cysts and arterial
      hypertension and whether their evacuation decreases the blood pressure (BP).
      METHODS: In a cross-sectional design, we analyzed 184 study participants with
      cysts and compared hypertensive and nonhypertensive among them. Outcomes were the
      number, the size and the location of a cyst. In a cross-over design, we first
      evaluated the change in absolute value of SBP, DBP and mean BP in 62 hypertensive
      patients who underwent percutaneous evacuation of a cyst and then the decrease of
      BP as a categorical variable that comprised all study participants. RESULTS:
      There were 55% giant renal cysts among hypertensive and 24% among nonhypertensive
      patients (P = 0.0001). The prevalence rates of multiple and peripheral cysts in
      hypertensive and nonhypertensive patients were similar to those of single and
      perihilar cysts, respectively. Significant differences in SBP, DBP and mean BP
      were found between pretreatment readings and 3 days, 1 month, 3 months and 6
      months after cyst evacuation (P < 0001). The differences were significant in all
      hypertensive patients (P < 0.001). There were less hypertensive patients 3 days
      after treatment than before treatment (P < 0.0001). CONCLUSION: An apparent
      association between the size of a simple renal cyst and hypertension was found,
      and aspiration of cysts resulted in a reduction of BP. Location and number of
      cysts were not related to BP.

PMID- 19584754
TI  - Renal and cardiovascular events: do they deserve the same consideration in
      clinical trials?

PMID- 19584755
TI  - Medication error reporting and the work environment in a military setting.
AB  - This study examined nurses' reasons for medication errors, reasons for not
      reporting errors, and perceived unit-reporting practices. It compared nurses'
      anonymous reports of medication errors with those from institutional reporting
      mechanisms. Qualities of the work environment, staffing, and workload were
      evaluated to determine associations with perceived error-reporting practices. The
      study findings have immediate applicability as a baseline for system
      improvements.

PMID- 19584753
TI  - Importance of pulsatility in hypertensive carotid artery growth and remodeling.
AB  - Arteries experience marked variations in blood pressure and flow during the
      cardiac cycle that can intensify during exercise, in disease, or with aging.
      Diverse observations increasingly suggest the importance of such pulsatility in
      arterial homeostasis and adaptations. We used a transverse aortic arch banding
      model to quantify chronic effects of increased pulsatile pressure and flow on
      wall morphology, composition, and biaxial mechanical properties in paired mouse
      arteries: the highly pulsatile right common carotid artery proximal to the band
      (RCCA-B) and the nearly normal left common carotid artery distal to the band
      (LCCA-B). Increased pulsatile mechanical stimuli in RCCA-B increased wall
      thickness compared with LCCA-B, which correlated more strongly with pulse (r* =
      0.632; P < 0.01) than mean (r* = 0.020; P = 0.47) or systolic (r* = 0.466; P <
      0.05) pressure. Similarly, inner diameter at mean pressure increased in RCCA-B
      and correlated slightly more strongly with a normalized index of blood velocity
      pulsatility (r* = 0.915; P < <0.001) than mean flow (r* = 0.834; P < 0.001).
      Increased wall thickness and luminal diameter in RCCA-B resulted from significant
      increases in cell number per cross-sectional area (P < 0.001) and collagen-to
      elastin ratio (P < 0.05) as well as a moderate (1.7-fold) increase in
      glycosaminoglycan content, which appears to have contributed to the significant
      decrease (P < 0.001) in the in-vivo axial stretch in RCCA-B compared with LCCA-B.
      Changes in RCCA-B also associated with a signficant increase in monocyte
      chemoattractant protein-1 (P < 0.05) whereas LCCA-B did not. Pulsatile pressure
      and flow are thus important stimuli in the observed three-dimensional arterial
      adaptations, and there is a need for increased attention to the roles of both
      axial wall stress and adventitial remodeling.

PMID- 19584757
TI  - Factors associated with pelvic asymmetry in transverse plane during gait in
      patients with cerebral palsy.
AB  - The purpose of this study was to describe the patterns of pelvic rotational
      asymmetry in the transverse plane and identify the possible factors related to
      this problem. One thousand and forty-five patients with cerebral palsy (CP) and
      complete documentation in the gait laboratory were reviewed in a retrospective
      study. Pelvic asymmetry in the transverse plane was observed in 52.7% of the
      patients; and to identify the possible causes of pelvic retraction, clinical
      (Thomas test, popliteal angle, and gastrocnemius tightness) and dynamic
      parameters (mean rotation of the hip in stance, minimum hip flexion, minimum knee
      flexion, and peak ankle dorsiflexion) were evaluated. The association between
      these parameters and pelvic retraction was assessed statistically. The results
      showed that 75.7% of patients with asymmetric pattern of the pelvis had clinical
      diagnosis of diplegic spastic CP. Among the patients with asymmetrical CP, the
      most common pattern was pelvic retraction on the affected side. The relationship
      between pelvic retraction and internal hip rotation was stronger in patients with
      asymmetrical diplegic CP than in those with hemiplegic (P<0.001) or symmetrical
      diplegic CP (P = 0.014). All of the patients exhibited a significant association
      among clinical parameters (Thomas test, popliteal angle, and gastrocnemius
      tightness) and pelvic retraction. In conclusion, pelvic retraction seems to be a
      multifactorial problem, and the etiology can change according to topographic
      classification, which must be taken into account during the decision-making
      process in patients with CP.

PMID- 19584756
TI  - Introduction of discharge plan to reduce adverse events within 72 hours of
      discharge from the ICU.
AB  - We examined the effect of introducing a discharge plan on the occurrence of
      adverse events within 72 hours of intensive care unit discharge. The study
      excluded discharges to home or to another institution and "not-for-resuscitation"
      patients. The adverse events rate was 23%, of which 37% were considered to be
      preventable. Respiratory problems and infections were the most frequent reasons.
      The discharge plan contributed to a change in the nature and preventability of
      events and facilitates the discharge process.

PMID- 19584758
TI  - Communication and adherence: moving from prediction to understanding.

PMID- 19584759
TI  - Comparing cost-utility estimates: does the choice of EQ-5D or SF-6D matter?
AB  - BACKGROUND: A number of different measures can be used within cost-utility
      analyses, we compared results according to both the EQ-5D and SF-6D. METHODS: A
      randomized trial was conducted to compare 4 options for people with knee pain.
      Over the 2 year trial period, the change in cost to health-service was estimated,
      and both the EQ-5D and SF-6D were used to estimate the change in quality-adjusted
      life years (QALYs). Using a complete case analysis, the cost-utility (incremental
      cost-effectiveness ratio [ICER]) of each option, according to both the EQ-5D and
      SF-6D, was calculated and assessed in relation to the cost-effectiveness
      threshold of pound20,000 per QALY. RESULTS: Of the 389 participants, 247 had
      complete cost, EQ-5D and SF-6D data. According to the EQ-5D, option 1 had an
      estimated ICER of pound10,815 (compared with option 4), option 2 was dominated by
      option 1, and option 3 was subject to extended dominance. Conversely, according
      to the SF-6D, option 3 had an ICER of pound9999 (compared with option 4), option
      2 had an ICER of pound36,883 (compared with option 3), and option 1 was subject
      to extended dominance. CONCLUSION: The EQ-5D and SF-6D estimated that different
      options (1 and 3, respectively) were cost-effective at the pound20,000 per QALY
      threshold, demonstrating that the choice of measure does matter.

PMID- 19584760
TI  - A longitudinal analysis of patient satisfaction and subsequent quality of life in
      Hong Kong Chinese breast and nasopharyngeal cancer patients.
AB  - BACKGROUND: We evaluated the longitudinal course of the relationship between
      patient satisfaction and quality of life (QoL) in Chinese breast and
      nasopharyngeal cancer patients. METHODS: A sample of Chinese breast (n = 250) and
      nasopharyngeal (n = 242) cancer patients were assessed during their first
      outpatient visit (baseline) and at 2 follow-up interviews (FU1 and FU2). The
      Chinese version of the Functional Assessment of Cancer Therapy-General Scale
      (FACT-G (Ch)) was adopted to assess QoL. Patient satisfaction was assessed by the
      9-item Chinese Patient Satisfaction Questionnaire (ChPSQ-9) and the cognitive
      subscale of the Medical Interview Satisfaction Scale (MISS-Cog). Linear mixed
      effects models were fitted to identify predictors of patient satisfaction and
      QoL. RESULTS: Recurrence after baseline (std beta = 0.58; 95% CI: 0.17, 0.98; P <
      0.05) was the only predictor of MISS-Cog, age (std beta = 0.01; 95% CI: 0.00,
      0.02; P < 0.05) and depressed mood (std beta = 0.20; 95% CI: 0.10, 0.30; P <
      0.001) of ChPSQ-9. After adjusting for sociodemographic and psychosocial
      variables, both ChPSQ-9 (std beta = 0.13; 95% CI: 0.07, 0.19; P < 0.001) and MISS
      Cog (std beta = 0.07; 95% CI: 0.02, 0.12; P < 0.05) independently predicted FACT
      G (Ch) scores. CONCLUSIONS: These findings suggest both general emotional support
      and informational support are important in predicting QoL among Chinese breast
      and nasopharyngeal cancer patients.

PMID- 19584761
TI  - Differential symptom reporting by mode of administration of the assessment:
      automated voice response system versus a live telephone interview.
AB  - BACKGROUND: Automated voice response (AVR) systems have been used to collect
      patient-reported outcome data. Mode of administration of the assessment may
      affect patient reporting. OBJECTIVE: To evaluate if there is a differential
      reporting of symptoms by the mode of assessment: AVR versus a live telephone
      interview among cancer patients with solid tumors undergoing chemotherapy.
      RESEARCH DESIGN: Randomized clinical trial comparing a nurse-assisted symptom
      management with an automated telephone symptom management. After completing
      intake telephone interview administered by a person, patients were randomized to
      either nurse arm or AVR arm to receive a 6-contact 8-week symptom management
      intervention. Patients in the nurse arm were called by specially trained nurses,
      and patients in the AVR arm were contacted via automated system to assess their
      symptoms and deliver symptom management strategies. SUBJECTS: Two hundred
      patients in nurse arm, and 186 patients in the AVR arm completed the first
      intervention contact. MEASURES: Severities of 14 cancer-related symptoms were
      rated by patients at intake interview and at first intervention contact before
      the receipt of any interventions. RESULTS: When compared with patients contacted
      by a nurse, patients contacted by the AVR reported higher severity of nausea and
      vomiting, diarrhea, poor appetite, constipation, diarrhea, pain, and alopecia
      controlling for prior intake symptom assessment that was free of mode effect.
      Symptom reporting varied by age, with the oldest group of patients reporting
      higher severity to the nurse. CONCLUSION: Mode effect needs to be considered in
      designing trials for symptom management and in symptom monitoring in clinical
      practice.

PMID- 19584762
TI  - Physician communication and patient adherence to treatment: a meta-analysis.
AB  - BACKGROUND: Numerous empirical studies from various populations and settings link
      patient treatment adherence to physician-patient communication. Meta-analysis
      allows estimates of the overall effects both in correlational research and in
      experimental interventions involving the training of physicians' communication
      skills. OBJECTIVES: Calculation and analysis of "r effect sizes" and moderators
      of the relationship between physician's communication and patient adherence, and
      the effects of communication training on adherence to treatment regimens for
      varying medical conditions. METHODS: Thorough search of published literature
      (1949-August 2008) producing separate effects from 106 correlational studies and
      21 experimental interventions. Determination of random effects model statistics
      and the detailed examination of study variability using moderator analyses.
      RESULTS: Physician communication is significantly positively correlated with
      patient adherence; there is a 19% higher risk of non-adherence among patients
      whose physician communicates poorly than among patients whose physician
      communicates well. Training physicians in communication skills results in
      substantial and significant improvements in patient adherence such that with
      physician communication training, the odds of patient adherence are 1.62 times
      higher than when a physician receives no training. CONCLUSION: Communication in
      medical care is highly correlated with better patient adherence, and training
      physicians to communicate better enhances their patients' adherence. Findings can
      contribute to medical education and to interventions to improve adherence,
      supporting arguments that communication is important and resources devoted to
      improving it are worth investing in. Communication is thus an important factor
      over which physicians have some control in helping their patients to adhere.

PMID- 19584763
TI  - Patient activation status as a predictor of patient experience among Medicare
      beneficiaries.
AB  - BACKGROUND: Patient activation status (PAS) can be identified using the Medicare
      Segmentation Screening Tool, a 2-item measure assessing patients' health skills
      and motivation to participate in their own care. OBJECTIVE: To determine whether
      PAS is predictive of Medicare beneficiary health care experiences with health
      providers and insurance plans after case-mix adjustment. RESEARCH DESIGN: Linear
      regression models examined the association between PAS and evaluations of care
      after case-mix adjustment in observational cross-sectional data. SUBJECTS:
      236,322 Medicare beneficiaries with at least one prescription medication
      responding to the Medicare Segmentation Screening Tool items on the 2007 Medicare
      Consumer Assessment of Healthcare Providers and Systems Survey. MEASURES: Four
      category patient activation category; 11 patient-reported evaluations of health
      care and providers and 2 self-reported immunization measures. RESULTS: PAS was
      strongly predictive of beneficiary experience beyond case-mix adjustment. Even
      after case-mix adjustment, active beneficiaries consistently reported the most
      positive experiences, followed by complacent beneficiaries, with differences of
      0.2 to 0.4 standard deviations for 4 of 5 composite measures of patient
      experience (P < 0.05). Adjusted immunization rates for flu and pneumonia were
      highest for active beneficiaries, followed closely by high-effort beneficiaries.
      The rates for these 2 segments were 10 percentage points higher than for
      complacent and passive beneficiaries. CONCLUSIONS: PAS may be an important
      determinant of health care experiences. More confident respondents (active and
      complacent) give higher ratings of their care and providers, suggesting that they
      have more favorable experiences. Respondent motivation (high for active and high
      effort) seems to be a factor in receiving preventive care.

PMID- 19584764
TI  - Components of care vary in importance for overall patient-reported experience by
      type of hospitalization.
AB  - BACKGROUND: Patients are hospitalized for disparate conditions and procedures.
      Patient experiences with care may depend on hospitalization type (HT).
      OBJECTIVES: Determine whether the contributions of patient experience composite
      measures to overall hospital ratings on the Hospital Consumer Assessment of
      Healthcare Providers and Systems Survey vary by HT. RESEARCH DESIGN: In cross
      sectional observational data, we defined 24 HTs using major diagnostic category
      and service line (medical, surgical, or obstetrical). To assess the importance of
      each composite for each HT, we calculated the simultaneous partial correlations
      of 7 composite scores with an overall hospital rating, controlling for patient
      demographics. SUBJECTS: Nineteen thousand seven hundred twenty English- or
      Spanish-speaking adults with nonpsychiatric primary diagnoses discharged home
      12/02-1/03 after an overnight inpatient stay in any of 132 general acute care
      hospitals in 3 states. MEASURES: Patient-reported doctor communication, nurse
      communication, staff responsiveness, physical environment, new medicines
      explained, pain control, and postdischarge information; overall 0 to 10 rating of
      care. RESULTS: Nurse communication was most important overall, with a 0.34
      average partial correlation (range: 0.17-0.49; P < 0.05 and among the 3 most
      important composites for all HTs). Discharge information was least important
      (0.05 average partial correlation; P < 0.05 for 10 of 24 HTs). Interactions
      demonstrated significant (P < 0.05) variation in partial correlations by HT for 5
      of 7 composites (all but responsiveness and environment), with nurse
      communication, doctor communication, and pain control showing the most variation
      (F > 2, P < 0.05). CONCLUSIONS: The importance of patient experience dimensions
      differs substantially and varies by HT. Quality improvement efforts should target
      those aspects of patient experience that matter most for each HT.

PMID- 19584765
TI  - Attributing sources of variation in patients' experiences of ambulatory care.
AB  - BACKGROUND: Public reporting and pay-for-performance programs increasingly rely
      on patient experience data to evaluate individual physicians and guide quality
      improvement efforts. The extent to which performance variation is attributable to
      physicians versus other system-level units, however, remains unclear. METHODS:
      Using ambulatory care experience survey data from 61,839 patients of 1729 primary
      care physicians in California (response rate = 39.1%), this study assesses the
      proportion of explainable performance variation attributable to various
      organizational units in composite measures of physician-patient interaction,
      organizational features of care, and global assessments of care. For each
      measure, multilevel regression models that controlled for respondent
      characteristics and used random effects to account for the clustering of patients
      within physicians, physicians within care sites, care sites within medical
      groups, and medical groups within primary care service areas, estimated the
      proportion of explainable performance variation attributable to each system-level
      unit. RESULTS: System-level factors explained between 27.9% to 47.7% of
      variation, with the highest proportion explained for the access to care composite
      and the lowest explained for the quality of chronic care composite. Physicians
      accounted for the largest proportion of explainable variance for all measures
      (range: 35.1%-49.0%). Care sites and primary care service areas explained
      substantial proportions of variance (>20% each) for the access to care and care
      coordination measures. Medical groups explained the largest proportions of
      variation (>20%) for global assessments of care. CONCLUSIONS: Individual
      physicians and their care sites are the most important foci for patient
      experience improvement efforts. Because markets contribute substantially to
      performance variation on organizational features of care, future research should
      clarify the extent to which associated performance deficits are modifiable.

PMID- 19584766
TI  - Predictive role of preoperative lymphoscintigraphy on the status of the sentinel
      lymph node in clinically node-negative patients with cutaneous melanoma.
AB  - We reviewed our experience to assess the predictive role of preoperative
      lymphoscintigraphy with regard to the pathological status of sentinel lymph node
      (sN) in patients with cutaneous melanoma, to optimize the surgical treatment
      planning with regard to the use of intraoperative frozen section examination of
      sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b
      T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of
      sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the
      ratio of radiotracer concentration within sN nodes as compared with the injection
      site. Our score allowed us to foresee that sN of patients with thick melanomas
      (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood
      (P<0.001) of harboring metastasis, whereas sN in patients with thin melanomas
      (T1b-T2) and high preoperative score (from L4 to L5) showed a 100% likelihood of
      being metastasis free. In conclusion, the sN is a reliable predictor of regional
      lymph node status in patients with cutaneous malignant melanoma. Moreover, we
      suggest that a low score (L1-L2-L3) associated with a thick melanoma is a good
      predictive factor of the positive sN involvement. This information could be
      useful in scheduling the intraoperative frozen-section examination with an
      expected benefit of a positive test in almost 90% of patients. Such patients
      might be selected for a 'one-stage' procedure with a more effective cost/benefit
      ratio and decreased hospitalization costs.

PMID- 19584767
TI  - The gallium complex KP46 exerts strong activity against primary explanted
      melanoma cells and induces apoptosis in melanoma cell lines.
AB  - The antineoplastic properties of gallium are well documented. Owing to their
      robust accumulation of gallium, melanoma cells should be amenable to gallium
      based anticancer drugs. With the aim of improving the disappointingly low
      activity of inorganic gallium salts, we have developed the orally bioavailable
      gallium complex KP46 [tris(8-quinolinolato)gallium(III)] that had already been
      successfully studied in a phase I clinical trial. To assess its therapeutic
      potential in malignant melanoma, its antiproliferative effects were investigated
      in series of human cell lines and primary explanted melanoma samples by means of
      the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and
      the Human Tumor Cloning Assay, respectively. When compared with other cell lines,
      the majority of melanoma cells rank among the KP46-sensitive cell lines (50%
      inhibitory concentration values: 0.8-3.7 micromol/l). Clinically achievable
      concentrations of KP46 proved to be highly effective in melanoma cells from
      primary explants of cutaneous and lymph node metastases. Colony growth was
      inhibited in 10 of 10 specimens by 5 micromol/l KP46 (corresponding to the steady
      state plasma concentration measured earlier in a study patient) and in four of 10
      specimens by 0.5 micromol/l KP46. In-vitro potency of KP46 is higher than that of
      dacarbazine or fotemustine and comparable with that of cisplatin. The effects
      induced by KP46 in melanoma cell lines involve cell-cycle perturbations (S-phase
      arrest) and apoptosis (activation of caspase-9, PARP [poly(ADP-ribose)
      polymerase] cleavage, formation of apoptotic bodies). No effects on DNA secondary
      structure could be observed in an electrophoretic mobility shift assay using
      double-stranded plasmid DNA. Thus, further studies on the therapeutic
      applicability of KP46 in malignant melanoma are warranted.

PMID- 19584769
TI  - Epithelial, stromal, and corneal pachymetry changes during orthokeratology.
AB  - PURPOSE: To describe epithelial, stromal, and corneal thickness profile changes
      induced by orthokeratology treatment. METHODS: This is a case report of a mild
      myopic patient (OD -3.25/-0.50 x 172 and OS -3.25/-0.50 x 45) treated with
      orthokeratology lenses. The patient was assessed before treatment (following 2
      weeks of no orthokeratology contact lens wear) and during treatment (after 30
      consecutive nights of wearing orthokeratology lenses). Epithelial, stromal, and
      corneal thickness profile in vivo was measured by Artemis very high-frequency
      digital ultrasound scanning across the central 10 mm diameter of the cornea
      before and during orthokeratology treatment. Manifest refraction, contrast
      sensitivity, corneal topography, and corneal front surface aberrations were also
      measured before and during orthokeratology treatment. Thickness changes were
      correlated with corneal topography changes and corneal front surface aberrations
      changes. The effects of these changes on the patient's quality of vision were
      measured with manifest refraction and contrast sensitivity. RESULTS:
      Orthokeratology lenses effectively corrected the patient's myopic refraction.
      Corneal topography demonstrated typical central flattening and an annulus of mid
      peripheral steepening in both the eyes. The epithelial thickness profile was
      altered, with up to 18 microm of central epithelial thinning and up to 16 microm
      of annular mid-peripheral epithelial thickening. There also appeared to be a
      degree of stromal changes, with central stromal thickening and mid-peripheral
      stromal thinning, in particular in the left eye. There was a large increase in
      higher order aberrations, in particular in the left eye. This was associated with
      a decrease in contrast sensitivity in both the eyes. CONCLUSIONS: Refractive
      changes during orthokeratology treatment are mainly induced by changes in
      epithelial thickness profile, while stromal changes may also contribute to a
      small extent.

PMID- 19584768
TI  - Magnetic resonance imaging diagnoses of bone scan abnormalities in breast cancer
      patients.
AB  - OBJECTIVE: To investigate the type of MR imaging diagnosis that corresponded to
      spinal lesions detected on a bone scan according to the number of lesions in
      breast cancer patients. MATERIALS AND METHODS: We retrospectively reviewed spinal
      MR images of 134 patients with breast cancer whose bone scans showed one or more
      spinal hot uptakes. The patients were grouped according to the number of spinal
      lesions detected on the bone scan: one or two lesions versus multiple (more than
      two) lesions. By using MR imaging, we determined the etiology of the spinal
      lesions in terms of being either benign or malignant. If the lesions were benign,
      we further categorized them into several specific pathologies. RESULTS: Sixty
      four (48%) of 134 patients had one or two spinal lesions as seen on a bone scan.
      On MR imaging, 45 (70%) of the 64 lesions had benign pathologies, whereas 19
      lesions (30%) were malignant. The benign pathologies in the 45 patients included
      facet arthrosis in 20 patients (44%), discovertebral degeneration in 12 patients
      (27%), compression fractures in eight patients (18%), and Schmorl's nodes in five
      patients (11%). Seventy (52%) of 134 patients had multiple spinal lesions as seen
      on the bone scan, and MR imaging revealed multiple bone metastases in 67 patients
      (96%) and facet arthrosis in three patients (4%). CONCLUSION: One or two spinal
      lesions seen on a bone scan in breast cancer patients are more likely to be
      benign pathologies such as facet arthrosis, discovertebral degeneration,
      compression fracture or Schmorl's node on MR imaging.

PMID- 19584770
TI  - Variants in COMT and spontaneous smoking cessation: retrospective cohort analysis
      of 925 cessation events.
AB  - Genome-wide studies have identified single nucleotide polymorphisms associated
      with smoking behaviour and nicotine dependence. Less is known about genetic
      determinants of smoking cessation, but rs4680 in COMT has recently been shown to
      explain a substantial proportion of the variation in cessation in the general
      population. We attempted to replicate the reported, clinically relevant effect in
      a population-based retrospective cohort analysis of 1443 ever-heavy smokers, of
      whom 925 had reached abstinence. In Cox regression models, neither rs4680 nor two
      polymorphisms nearby were associated with smoking cessation. The adjusted
      relative cessation rate (95% confidence interval) in rs4680 methionine carriers
      in reference to valine homozygotes was 0.97 (0.83-1.12). The absence of a
      significant effect of rs4680 in this statistically well-powered study - the 95%
      confidence interval even excluding the previously reported effect - highlights
      the need for rigorous replication efforts and suggests that rs4680 genotype
      should not yet be considered informative for smoking patient care.

PMID- 19584771
TI  - Pharmacokinetic and pharmacodynamic basis for overcoming acetaldehyde-induced
      adverse reaction in Asian alcoholics, heterozygous for the variant ALDH2*2 gene
      allele.
AB  - OBJECTIVES: It has been well documented that although homozygosity of the variant
      aldehyde dehydrogenese-2 (ALDH2) gene allele, ALDH2*2, in Asians almost fully
      protects against alcoholism, the heterozygosity only affords a partial protection
      to varying degrees. The partial protection against alcoholism has been ascribed
      to the faster elimination of acetaldehyde by residual hepatic ALDH2 activity and
      the lower accumulation in circulation in nonalcoholic heterozygotes. The
      physiological basis for overcoming the protection in ALDH2*1/*2 alcoholics,
      however, remains unclear. METHODS: To address this question, we recruited a total
      of 27 Han Chinese alcohol-dependent men, matched by age and body mass index,
      controlled for normal liver and cardiovascular functions, from a population base
      of 221 alcoholics. The participants were divided into ALDH2*1/*1 homozygotes (n =
      13) and ALDH2*1/*2 heterozygotes (n = 14). After a moderate dose of ethanol (0.5
      g/kg body weight), blood ethanol/acetaldehyde/acetate concentrations, cardiac and
      extracranial/intracranial arterial hemodynamic parameters, as well as self-rated
      subjective sensations, were measured for 130 min. RESULTS: ALDH2*1/*2 alcoholics
      exhibited significantly higher blood acetaldehyde levels as well as prominent
      cardiovascular effects and the subjective perceptions, compared with the
      ALDH2*1/*1 alcoholics. Comparable profiles of blood acetaldehyde were found
      between heterozygotic alcoholics and the previously reported nonalcoholic
      heterozygotes intaking the same dose of ethanol. ALDH2*1/*2 alcoholics revealed,
      however, significantly lower intensities in both physiologic and psychologic
      responses than did the nonalcoholic heterozygotes. CONCLUSION: These results
      indicate that acetaldehyde, rather than ethanol or acetate, is primarily
      responsible for the observed alcohol sensitivity reactions in heterozygotic
      alcoholics and suggest that physiological tolerance and/or innate low sensitivity
      may play a crucial role in overcoming the deterring response. A potential
      pharmacogenetic classification of acetaldehydism and alcoholism for alcoholics
      carrying the different ALDH2 genotypes is proposed.

PMID- 19584772
TI  - Evaluation of variable-dose treatment with a new U.S. Botulinum Toxin Type A
      (Dysport) for correction of moderate to severe glabellar lines: results from a
      phase III, randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: In April, the U.S. Food and Drug Administration approved a new U.S.
      formulation of botulinum neurotoxin type A (Dysport; Medicis Aesthetics, Inc.,
      Scottsdale, Ariz.). This formulation has demonstrated inhibition of glabellar
      lines at a 50-unit dose. Standard clinical practice is to adjust the dose based
      on muscle mass. METHODS: Patients stratified by race/ethnicity were randomized to
      receive a single treatment of Dysport administered in various doses or placebo.
      Dysport was administered in a total volume of 0.4 to 0.6 ml for women (50, 60, or
      70 units) and 0.5 to 0.7 ml for men (60, 70, or 80 units), based on
      procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and
      patient self-evaluation on days 14, 30, 60, 90, 120, and 150 after treatment.
      RESULTS: At day 30, 85 percent and 87 percent of Dysport-treated patients were
      responders as assessed by blinded evaluator and patient self-evaluation,
      respectively, compared with 3 percent and 5 percent of placebo-treated patients,
      respectively (p < 0.001). Median duration of effect was 109 days for Dysport
      versus 0 days for placebo (blinded evaluator) and 107 days for Dysport versus 0
      days for placebo (patient self-evaluation). Response and duration of action were
      slightly higher in African American patients. The majority of treatment-emergent
      adverse events were mild or moderate in severity. CONCLUSION: A single treatment
      with Dysport, with the dose based on gender and muscle mass, is well tolerated
      and provides a greater and longer-lasting improvement in glabellar lines compared
      with placebo.

PMID- 19584773
TI  - Association between the serotonin 2A receptor gene and bipolar affective disorder
      in an Australian cohort.
AB  - OBJECTIVE: The serotonin 2A receptor gene (HTR2A) is involved in serotonergic
      neurotransmission, and has been targeted as a functional candidate for mood
      disorders because of the extensive support for the involvement of serotonin in
      mood regulation. We previously reported linkage evidence for a bipolar affective
      disorder susceptibility locus on chromosome 13q, which harbours HTR2A, thus
      making the gene both a positional and functional candidate. We assessed HTR2A for
      association in an Australian bipolar disorder case-control cohort. METHODS:
      Single nucleotide polymorphisms (SNPs) were selected across HTR2A exons and
      introns, and were investigated for association in an Australian cohort of 218
      cases and 166 healthy controls. SNP haplotypes were also examined for
      association. RESULTS: Significant association of rs2224721 (P = 0.02) and
      borderline significance of rs1923886 (P = 0.05) were observed. The former
      remained significant after multiple testing corrections using the rough False
      Discovery Rate method, but did not exceed the more conservative Bonferroni's
      correction threshold. Haplotype association analysis suggests that the haplotype
      CCGCA (at SNPs rs3125, rs6314, rs1923886, rs2224721 and rs2770296) is protective
      against bipolar disorder (P = 0.021, odds ratio 0.63) and the rarer haplotype
      CCACG confers risk to the disorder (P = 0.0065, odds ratio 3.08). CONCLUSION: We
      found that HTR2A is associated with bipolar disorder. The HTR2A gene should not
      be excluded as a potential susceptibility gene for bipolar disorder despite a
      number of conflicting association results.

PMID- 19584774
TI  - Association and expression studies of glutamate-cysteine ligase modifier (GCLM)
      and schizophrenia in the Chinese Han population.

PMID- 19584775
TI  - Adding insult to injury: care of patients with acute kidney injury.

PMID- 19584776
TI  - Venous thromboembolism: not as easy as it looks.

PMID- 19584778
TI  - Management of venous thromboembolism in patients with cancer.
AB  - The association between venous thromboembolism and cancer has been recognized for
      over 140 years. This article reviews current prevention, diagnosis and treatment
      of cancer-related venous thromboembolism, and highlights emerging anticoagulants
      and the possible anticancer effects of anticoagulants such as low molecular
      weight heparins.

PMID- 19584779
TI  - Venous thromboembolism: a UK perspective.
AB  - Venous thromboembolism remains a significant cause of morbidity and mortality in
      the UK, and its dangers, particularly in hospitalized patients, have long been
      recognized. Recent measures to tackle this problem and new treatments should
      alleviate the burden of venous thromboembolism for patients, their families and
      hospital services.

PMID- 19584780
TI  - Practical prescribing of intravenous unfractionated heparin.
AB  - Intravenous unfractionated heparin is sometimes poorly managed in NHS hospitals.
      This article investigates why this is so and reviews the evidence for optimal
      unfractionated heparin prescribing, using it to make some suggestions as to how
      doctors can improve this.

PMID- 19584781
TI  - Managing immunosuppression in medical patients.
AB  - Immunosuppressive drugs are increasingly widely used. Safe use requires knowledge
      of the side-effect profile, contraindications and precautions before starting,
      and the monitoring regimen, and patients should be fully informed of the risks
      and benefits before starting.

PMID- 19584782
TI  - Recent initiatives to reduce the spread of meticillin-resistant Staphylococcus
      aureus.
AB  - Recent initiatives have achieved marked reductions in meticillin-resistant
      Staphylococcus aureus bacteraemias. However, the relative effectiveness of
      prevention interventions is unclear. Initiatives to control meticillin-resistant
      Staphylococcus aureus have tended to ignore the benefits of altering
      antimicrobial prescribing.

PMID- 19584784
TI  - Setting learning objectives.
AB  - Clinical teachers may be involved with students and trainees on a variety of
      different programmes who are required to achieve a diverse range of learning
      outcomes or objectives. Teachers who better understand the relationship between
      learning outcomes and the planning and delivery of educational activities can
      help learners receive more from their education and training.

PMID- 19584783
TI  - Transient osteoporosis of the foot.
AB  - Transient osteoporosis is a rare cause of pain in the foot. There is a broad
      differential diagnosis. A multidisciplinary assessment by both an orthopaedic
      surgeon and rheumatologist with review of the imaging by a radiologist is useful,
      as this condition is a diagnosis of exclusion.

PMID- 19584785
TI  - Working as a newly appointed consultant: a study into the transition from
      specialist registrar.
AB  - Practising for the first time as a consultant can be extremely challenging. This
      study explored the experiences of 45 physicians and surgeons who had made the
      transition from specialist registrar to hospital consultant.

PMID- 19584787
TI  - When headaches are not neurological: an unusual presentation of Ebstein's
      anomaly.

PMID- 19584786
TI  - Leopold Auenbrugger, father of the clinical examination of the chest.

PMID- 19584788
TI  - An unusual case of acute onset lower lip numbness.

PMID- 19584789
TI  - Mittelschmerz mimicking appendicitis.

PMID- 19584790
TI  - Mental Capacity Act: a must for all.

PMID- 19584792
TI  - Should patients be manually ventilated during rapid sequence induction of
      anaesthesia?
AB  - Pulmonary aspiration of gastric contents has been recognized as a cause of
      significant morbidity and mortality during anaesthesia since the classic
      publication by Mendelson in 1946. The introduction of suxamethonium 5 years later
      allowed tracheal intubation to be achieved under complete muscle relaxation
      within 1 minute of induction of anaesthesia. In 1961 Sellick described the use of
      cricoid pressure to prevent gastric regurgitation.

PMID- 19584793
TI  - Serum or plasma urea and electrolytes.

PMID- 19584794
TI  - General management of acute kidney injury.

PMID- 19584795
TI  - Orbital cellulitis: assessment and management.

PMID- 19584796
TI  - A shift in the life of a medical student working as a health-care assistant.

PMID- 19584797
TI  - So you want to be ... a cardiologist.

PMID- 19584798
TI  - Managing your pay: a guide for the foundation year doctor.

PMID- 19584799
TI  - Smell and taste disorders. Changes in senses can often be treated.

PMID- 19584800
TI  - Statin medications may improve stroke outcomes, recovery.

PMID- 19584801
TI  - Regularly consuming red meat could have health consequences.

PMID- 19584802
TI  - Weight loss depends on cutting calories, not following latest fad.

PMID- 19584803
TI  - Health care in a pinch. Investments that won't break your budget.

PMID- 19584804
TI  - Mayo Clinic office visit. Carpal tunnel syndrome. An interview with Russell
      Gelfman, M.D.

PMID- 19584805
TI  - Emotional eating. Look beyond food for comfort.

PMID- 19584806
TI  - Can I get swimmer's itch from swimming in a lake?

PMID- 19584807
TI  - What does it mean to have "dense breasts?".

PMID- 19584808
TI  - An interview with Nobel laureate Douglas Osheroff, Physics 1996.
AB  - At extremely low temperatures, certain materials conduct electrical currents
      without resistance - a phenomenon called superconductivity. An analogous state
      occurs in extremely low-temperature fluids, in which molecules flow without
      internal friction or resistance. Such a state, termed superfluidity, was
      predicted for helium-3 shortly after the Bardeen, Cooper, and Schrieffer (BCS)
      theory of 1957 explained the superconductivity of metals. The search for helium-3
      superfluidity commenced; it continued for about ten years without success, and
      was all but abandoned by the time Douglas D. Osheroff began his graduate studies
      at Cornell University. "The general wisdom was that the superfluidity of helium-3
      was a pipe dream of the theorists," says Osheroff. "But in fact, it did occur."
      In 1972, Osheroff - together with David M. Lee and Robert C. Richardson -
      demonstrated the transition of helium-3 to a superfluid state at temperatures
      near absolute zero (-273 degrees C). Twenty-four years after their discovery,
      Osheroff and colleagues won the Nobel Prize in Physics. Osheroff's scientifically
      inquisitive nature developed long before his landmark discovery. "A lot of people
      did crazy things when they were young" says Osheroff, whose wild experimentation
      including building a 100,000-volt X-ray machine as a teenager. Now as a faculty
      member at Stanford University, Osheroff stresses the importance of mentoring
      undergraduates to get them excited about science, and to guide them on what to do
      next. As for graduate school, Osheroff says that "it doesn't matter what is it
      that you study as a graduate student - the important thing is learning how to
      study."

PMID- 19584809
TI  - Generation of single-cell suspensions from mouse neural tissue.
AB  - Within the nervous system, hundreds of neuronal and glial cell types have been
      described. Each specific cell type in the brain or spinal cord has a repertoire
      of cell surface molecules, or molecular determinants, through which it can be
      identified and characterized. Currently, robust cell identification and
      separation technologies require single-cell preparations to be generated while
      simultaneously limiting cell death and destruction of characteristic surface
      protein. The gentleMACS Dissociator, when used in combination with trypsin or
      papain-based dissociation kits, can effectively and gently dissociate brain
      tissue while preserving antigen epitopes and limiting cell loss. Standardized
      preparation of single-cell suspensions is achieved using C Tubes and optimized,
      preset gentleMACS Programs. Once generated, single-cell suspensions can be
      treated with monoclonal conjugates like Anti-Prominin-1 MicroBeads, which
      identify neural progenitors, or purified further using Myelin Removal Beads.

PMID- 19584810
TI  - The genetics of quantitative traits: challenges and prospects.
AB  - A major challenge in current biology is to understand the genetic basis of
      variation for quantitative traits. We review the principles of quantitative trait
      locus mapping and summarize insights about the genetic architecture of
      quantitative traits that have been obtained over the past decades. We are
      currently in the midst of a genomic revolution, which enables us to incorporate
      genetic variation in transcript abundance and other intermediate molecular
      phenotypes into a quantitative trait locus mapping framework. This systems
      genetics approach enables us to understand the biology inside the 'black box'
      that lies between genotype and phenotype in terms of causal networks of
      interacting genes.

PMID- 19584811
TI  - Quantitative approaches in developmental biology.
AB  - The tissues of a developing embryo are simultaneously patterned, moved and
      differentiated according to an exchange of information between their constituent
      cells. We argue that these complex self-organizing phenomena can only be fully
      understood with quantitative mathematical frameworks that allow specific
      hypotheses to be formulated and tested. The quantitative and dynamic imaging of
      growing embryos at the molecular, cellular and tissue level is the key
      experimental advance required to achieve this interaction between theory and
      experiment. Here we describe how mathematical modelling has become an invaluable
      method to integrate quantitative biological information across temporal and
      spatial scales, serving to connect the activity of regulatory molecules with the
      morphological development of organisms.

PMID- 19584812
TI  - Lentiviral vectors transduce proliferating dendritic cell precursors leading to
      persistent antigen presentation and immunization.
AB  - Lentiviral vectors (LVs) are tools for in vivo gene delivery, to correct genetic
      defects or to deliver antigens for vaccination. It was reported that systemic
      injection of LVs in mice transduced cells in liver and spleen. Here we describe
      the reasons for, and consequences of, persistent gene expression in spleen. After
      5 days of intravenous injection, a green fluorescence protein (GFP)-expressing LV
      was detected in lymphocytes, macrophages and all subsets of dendritic cells (DCs)
      in spleen. In the case of macrophages and DCs, the percentage of transduced cells
      increased between 5 and 30 days after injection. We used bromodeoxyuridine (BrdU)
      incorporation to show that the macrophages were largely nondividing, whereas the
      transduced DCs arose from dividing precursor cells and could be detected in
      spleen 2 months after injection. Expression of ovalbumin (OVA) in the LV reduced
      the number of transduced DCs in spleen after 30 days. However, the remaining
      transduced cells stimulated proliferation and activation of OVA-specific CD8(+) T
      cells transferred 2 months after LV injection. The mice also maintained cytolytic
      activity against OVA-pulsed targets. These results show that LVs transduce DC
      precursors, which maintain transduced DCs in spleen for at least 2 months,
      leading to prolonged antigen presentation and effective T-cell memory.

PMID- 19584814
TI  - Mesenchymal stem cells arrest intervertebral disc degeneration through
      chondrocytic differentiation and stimulation of endogenous cells.
AB  - Degenerative disc disease (DDD) is a common disease which affects millions of
      people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have
      been shown to have the ability to arrest degeneration in rabbit and canine
      intervertebral discs. In this study, we have used the mouse model to investigate
      the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were
      injected into the degenerated murine intervertebral discs induced by annular
      puncture. We found that BMSC could arrest the progressive degeneration of the
      discs with significant regeneration of the nucleus pulposus (NP). In the
      regeneration, expression of proteoglycan genes were upregulated and extracellular
      matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined
      in situ hybridization and immunohistochemistry revealed that BMSC underwent
      chondrocytic differentiation in the regeneration process. Interestingly, BMSC
      induced an increase of endogenous notochordal cells in NP and expression of
      chondrocytic markers. In this study, we have firstly shown that the BMSC could
      arrest the degeneration of the murine notochordal NP and contribute to the
      augmentation of the ECM in the NP by both autonomous differentiation and
      stimulatory action on endogenous cells.

PMID- 19584813
TI  - Drug delivery-mediated control of RNA immunostimulation.
AB  - RNA interference (RNAi) has generated significant interest as a strategy to
      suppress viral infection, but in some cases antiviral activity of unmodified
      short-interfering RNA (siRNA) has been attributed to activation of innate immune
      responses. We hypothesized that immunostimulation by unmodified siRNA could
      mediate both RNAi as well as innate immune stimulation depending on the mode of
      drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs)
      to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1)
      formulated with unmodified siRNA targeting the influenza nucleoprotein gene
      exhibited antiviral activity. Formulations were optimized to increase antiviral
      activity, but the antiviral activity of lipidoid-delivered siRNA did not depend
      on sequence homology to the influenza genome as siRNA directed against unrelated
      targets also suppressed influenza replication in vivo. This activity was
      primarily attributed to enhancement of innate immune stimulation by lipidoid
      mediated delivery, which indicates increased toll-like receptor (TLR) activation
      by siRNA. Certain chemical modifications to the siRNA backbone, which block
      TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated
      antiviral activity despite enhanced lipidoid-mediated delivery. Here, we
      demonstrate that innate immune activation caused by unmodified siRNA can have
      therapeutically relevant effects, and that these non-RNAi effects can be
      controlled through chemical modifications and drug delivery.

PMID- 19584816
TI  - Dose optimization for long-term rAAV-mediated RNA interference in the
      nigrostriatal projection neurons.
AB  - Short-hairpin RNA (shRNA)-mediated gene knockdown is a powerful tool for targeted
      gene silencing and an emerging novel therapeutic strategy. Recent publications,
      however, reported unexpected toxicity after utilizing viral-mediated shRNA
      knockdown in vivo. Thus, it is currently unclear whether shRNA-mediated knockdown
      strategy can be used as a safe and efficient tool for gene silencing. In this
      study, we have generated rAAV vectors expressing shRNAs targeting the rat
      tyrosine hydroxylase (TH) mRNA (shTH) for testing the efficacy of in vivo TH
      knockdown in the nigral dopaminergic neurons. At high titers, not only the shTH
      vectors but also the scrambled and green fluorescence protein (GFP)-only controls
      caused cell death. In a dose-response study, we identified a dose window leading
      to >60% decrease in TH(+) neurons without any change in vesicular monoamine
      transporter-2 (VMAT2) expression. Moreover, using the safe and efficient dose, we
      showed that dopamine (DA) synthesis rate was significantly reduced and this lead
      to emergence of motor deficits in the shTH-expressing rats. Interestingly, these
      animals showed very robust and long-lasting recovery after a single systemic L
      3,4-dihydroxyphenylalanine (L-DOPA) administration beyond what can be achieved in
      6-hydroxydopamine (6-OHDA)-lesioned rats. Our results have implications for both
      mechanistic and therapeutic studies utilizing long-term shRNA-mediated gene
      silencing in the nigrostriatal projection system.

PMID- 19584815
TI  - Mesenchymal stromal cells as supportive cells for hepatocytes.
AB  - Hepatocytes and hematopoietic stem cells (HSCs) appear to share many of the same
      requirements for their survival, functionality, and proliferation. This may be
      due to a shared location during fetal development. Moreover, hepatocytes and HSCs
      are unable to function, or even survive, without stromal cell support. Bone
      marrow-derived mesenchymal stromal cells (MSCs) support the proliferation and
      functionality, not only of HSCs, but also of hepatocytes. Although knowledge of
      the mechanisms underlying HSCs' support is far more advanced than for
      hepatocytes, data suggest that many agents important for HSCs also maintain the
      normal hepatocyte phenotype in vitro. Thus, it is possible that new techniques
      for the maintenance and expansion of HSCs may also be useful for hepatocytes.
      Bone marrow-derived MSCs are easily cultured and expanded in vitro, and some data
      suggest that they are immunoregulatory as well as relatively nonimmunogenic.
      These observations suggest that allogeneic MSCs may be useful not only in
      supporting hepatocyte growth and proliferation but also in modulating immune
      responses such as stellate cell activation.

PMID- 19584817
TI  - Regulation of adult hematopoietic stem cells fate for enhanced tissue-specific
      repair.
AB  - The ability to control the differentiation of adult hematopoietic stem cells
      (HSCs) would promote development of new cell-based therapies to treat multiple
      degenerative diseases. Systemic injection of NaIO(3) was used to ablate the
      retinal pigment epithelial (RPE) layer in C57Bl6 mice and initiate neural retinal
      degeneration. HSCs infected ex vivo with lentiviral vector expressing the RPE
      specific gene RPE65 restored a functional RPE layer, with typical RPE phenotype
      including coexpression of another RPE-specific marker, CRALBP, and photoreceptor
      outer segment phagocytosis. Retinal degeneration was prevented and visual
      function, as measured by electroretinography (ERG), was restored to levels
      similar to that found in normal animals. None of the controls (no HSCs, HSCs
      alone and HSCs infected with lentiviral vector expressing LacZ) showed these
      effects. In vitro gene array studies demonstrated that infection of HSC with
      RPE65 increased adenylate cyclase mRNA. In vitro exposure of HSCs to a
      pharmacological agonist of adenylate cyclase also led to in vitro differentiation
      of HSCs to RPE-like cells expressing pigment granules and the RPE-specific
      marker, CRALBP. Our data confirm that expression of the cell-specific gene RPE65
      promoted fate determination of HSCs toward RPE for targeted tissue repair, and
      did so in part by activation of adenylate cyclase signaling pathways. Expression
      by HSCs of single genes unique to a differentiated cell may represent a novel
      experimental paradigm to influence HSC plasticity, force selective
      differentiation, and ultimately lead to identification of pharmacological
      alternatives to viral gene delivery.

PMID- 19584818
TI  - Nucleofection of DCs to generate Multivirus-specific T cells for prevention or
      treatment of viral infections in the immunocompromised host.
AB  - Viral infections cause morbidity and mortality in allogeneic hematopoietic stem
      cell transplant (HSCT) recipients. To prevent and treat these, we have produced
      and infused cytotoxic T lymphocytes (CTLs) with specificity for Epstein-Barr
      virus (EBV), cytomegalovirus (CMV), and adenovirus (Adv), and shown that small
      numbers of infused cells proliferate in vivo and protect against all three
      viruses. Despite these encouraging results, broader implementation of this
      approach is limited by the need for infectious virus material (EBV), expensive
      production of clinical grade adenoviral vectors, and a prolonged (8-12 weeks)
      period of manufacture. There is also competition between virus-derived antigens
      within antigen-presenting cells (APCs), limiting extension to additional agents.
      We now describe an approach that uses DNA nucleofection of dendritic cells (DCs)
      with DNA plasmids that encode a range of immunodominant and subdominant viral
      antigens from CMV, EBV, BK, and Adv. Within 10 days, this methodology provides
      multivirus-reactive CTLs that lack alloreactivity. We further demonstrate that
      nucleofected DC stimulation can be combined with interferon-gamma (IFN-gamma)
      capture technology to produce even more rapid multivirus-CTL products for
      treatment of acute infection. These CTL generation procedures should increase the
      feasibility and applicability of T-cell therapy.

PMID- 19584820
TI  - Comparison between filgrastim and lenograstim plus chemotherapy for mobilization
      of PBPCs.
AB  - Recombinant human (rHu) G-CSF has been widely used to treat neutropenia and
      mobilize PBPCs for their autologous and allogeneic transplantation. It shortens
      neutropenia and thus reduces the frequency of neutropenic fever. We compared the
      efficiency of glycosylated rHu and non-glycosylated Hu G-CSF in mobilizing
      hematopoietic progenitor cells (HPCs). In total, 86 patients were consecutively
      enrolled for mobilization with CY plus either glycosylated or non-glycosylated G
      CSF, and underwent leukapheresis. The HPC content of each collection, toxicity,
      days of leukapheresis needed to reach the minimum HPC target and days to recover
      WBC (> or =500 and >1000/mm(3)) and plts (>50 000/mm(3)) were evaluated.
      Glycosylated G-CSF mobilized more CD34+ cells than did the non-glycosylated form.
      The ability to reach a collection target of >3 x 10(6) CD34+/kg body weight in
      two leukaphereses was higher for glycosylated G-CSF. No significant differences
      between the two regimens were observed with regard to toxicity and days to WBC
      and plt recovery. High-dose CY plus glycosylated G-CSF achieved adequate
      mobilization and the collection target more quickly and with fewer leukaphereses.

PMID- 19584821
TI  - Influence of GST gene polymorphisms on busulfan pharmacokinetics in children.
AB  - Busulfan (BU) is a key compound in conditioning myeloablative regimens for
      children undergoing hematopoietic stem cell transplantation (HSCT). There are
      wide interindividual differences in BU pharmacokinetics, which increase the risk
      of veno-occlusive disease, graft rejection and disease relapse. As BU is mainly
      metabolized by glutathione S-transferase (GST), it is hypothesized that
      functional polymorphisms in GST genes may explain in part the variability in BU
      pharmacokinetics. We analyzed polymorphisms in GSTA1 (C-69T, A-513G, G-631T, C
      1142G), GSTM1 (deletion) and GSTP1 (A1578G, C2293T) genes in 28 children
      undergoing HSCT. All patients had individualized dosing based on pharmacokinetics
      after the first dose of intravenous BU. GSTM1-null individuals had higher drug
      exposure (P(Cmax)=0.008; P(AUC)=0.003; P(Css)=0.02) and lower clearance
      (P(CL)=0.001). Multivariate regression models showed that, other than the drug
      dose and age, the GSTM1 genotype was the best predictor of first-dose
      pharmacokinetic variability. GSTM1-null patients also received lower cumulative
      BU doses (P=0.02). No association was found between BU exposure and major GSTA1
      or GSTP1 gene variants. In children, GSTM1 polymorphism seems to modify BU
      pharmacokinetics after intravenous drug administration.

PMID- 19584822
TI  - Prompt recovery of recipient hematopoiesis after two consecutive haploidentical
      peripheral blood SCTs in a child with leukocyte adhesion defect III syndrome.

PMID- 19584819
TI  - Strategies to modulate immune responses: a new frontier for gene therapy.
AB  - The success of gene therapy strategies to cure disease relies on the control of
      unwanted immune responses to transgene products, genetically modified cells
      and/or to the vector. Effective treatment of an established immune response is
      much harder to achieve than prevention of a response before it has had a chance
      to develop. However, preventive strategies are not always effective in avoiding
      immune responses, thus the use of drugs to induce immunosuppression (IS) is
      required. The growing discovery of novel drugs provides a conceptual shift from
      using generalized, moderately intensive immunosuppressive regimens towards a
      refined approach to attain the optimal balance of naive cells, effector cells,
      memory cells, and regulatory cells, harnessing the natural tolerance mechanisms
      of the body. We review several strategies based on transient IS coupled with gene
      therapy for sustained immune tolerance induction to the therapeutic transgene.

PMID- 19584823
TI  - Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit
      anti-thymocyte globulin, given on day+7 after alternative donor transplants.
AB  - We have previously shown that hemopoietic stem cell transplant (HSCT) recipients
      can be stratified on day+7 as having low, intermediate or a high risk of
      transplant-related mortality (TRM). With the aim of reducing TRM and GVHD,
      intermediate and high-risk patients (n=170) were randomized to receive anti
      thymocyte globulin (ATG, thymoglobuline) on day+7 (n=84) or no treatment (n=86)
      (controls). There was a reduction of TRM from 35% in controls to 29% in ATG
      patients (P=0.3), of acute GVHD III-IV from 15 to 5% (P=0.02) and of chronic GVHD
      from 26 to 11% (P=0.03); survival was comparable. The predictive value of the
      day+7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high
      risk, respectively, P=0.03), whereas ATG abrogated this predictive effect (29 vs
      29%). ATG reduced GVHD (P=0.006) in high-risk patients, but not in patients with
      an intermediate risk. In conclusion, we confirm that TRM can be predicted on the
      basis of day+7 laboratory values, after alternative donor HSCT; in high-, but not
      intermediate-risk patients, the administration of ATG on day+7 reduces GVHD.
      These results may represent a platform for risk-adapted post transplant immune
      modulation.

PMID- 19584824
TI  - Allogeneic and autologous transplantation for haematological diseases, solid
      tumours and immune disorders: current practice in Europe 2009.
AB  - The European Group for Blood and Marrow Transplantation regularly publishes
      special reports on the current practice of haematopoietic SCT for haematological
      diseases, solid tumours and immune disorders in Europe. Major changes have
      occurred since the first report was published. HSCT today includes grafting with
      allogeneic and autologous stem cells derived from BM, peripheral blood and cord
      blood. With reduced-intensity conditioning regimens in allogeneic
      transplantation, the age limit has increased, permitting the inclusion of older
      patients. New indications have emerged, such as autoimmune disorders and AL
      amyloidosis for autologous HSCT and solid tumours, myeloproliferative syndromes
      and specific subgroups of lymphomas for allogeneic transplants. The introduction
      of alternative therapies, such as imatinib for CML, has challenged well
      established indications. An updated report with revised tables and operating
      definitions is presented.

PMID- 19584825
TI  - Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective
      and leads to an increase of activated NK (NKp44(+)) and T (HLA-DR(+)) cells.
AB  - We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated
      myeloma patients with a median age of 59 years (range: 37-70) and relapse after
      allo-SCT. Lenalidomide was given at a dose of 15 mg (n=4), or 25 mg (n=20),
      orally once daily on day 1 to day 1 every 28 days, with (n=20) or without (n=4)
      DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side
      effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and
      thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were
      observed in 50%. Non-hematological toxicity consisted of muscle cramps (n=9),
      fatigue (n=5) and constipation (n=2). Mild grade I-II GVHD was seen in three
      patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in
      13%. The median time to progression was 9.7 months (95% confidence interval (CI):
      7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring
      after lenalidomide showed significant increase of activated NK (NKp44(+)) and T
      (HLA-DR(+)) cells, as well as regulatory T cells (CD4(+), CD25(+), CD127(lo)),
      supporting an immunomodulating anti-myeloma effect of lenalidomide.

PMID- 19584826
TI  - Prior treatment with gemtuzumab ozogamicin and the risk of veno-occlusive disease
      after allogeneic haematopoietic stem cell transplantation.
AB  - This was a retrospective multicenter study including 44 acute leukaemia patients
      who have received allogeneic haematopoietic SCT (allo-HSCT) after prior exposure
      to Gemtuzumab Ozogamicin (GO) + chemotherapy. Median interval between last
      administration of GO and allo-HSCT was 4.2 (range, 0.8-26.3) months. At time of
      allo-HSCT, 33 patients were in CR. The majority of patients (n=36) received a
      reduced-intensity conditioning (RIC) regimen before allo-HSCT. All but one
      patient received low-dose heparin for veno-occlusive disease (VOD) prophylaxis.
      With a median follow-up of 15 (range, 1.1-63) months, overall survival and
      disease-free survival after allo-HSCT were 45% (95% confidence interval (CI), 30
      61%) and 38% (95% CI, 24-54%) at 2 years, respectively. The cumulative incidence
      of grade 3-4 hyperbilirubinemia was 13.5% (n=6), with this being 21% in patients
      with a short (< or =3.5 months) GO-allo-HSCT interval (n=4/19) vs 8% in all
      others (P=NS). Overall, the cumulative incidence of VOD was 7% (n=3), with this
      being 10.5% (n=2/19) in patients with a short GO-allograft interval (< or =3.5
      months) vs 4% (n=1/25) for all others (P=NS), and 5.5% (n=2/36) in patients
      receiving an RIC regimen vs 12.5% for the others (n=1/8) (P=NS). These results
      suggest that GO-based chemotherapy before allo-HSCT is feasible and does not
      result in an excessive rate of liver toxicity, especially VOD, after allo-HSCT.

PMID- 19584827
TI  - Brazilian experience with two conditioning regimens in patients with multiple
      sclerosis: BEAM/horse ATG and CY/rabbit ATG.
AB  - Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an
      intensive immunosuppressive therapy to treat refractory patients and to prevent
      the progression of multiple sclerosis (MS). This is a prospective multicentric
      Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and
      CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary
      progressive MS subtype and the mean age was 42 years. The baseline EDSS score in
      58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively.
      The complication rate during the intra-transplantation period was 56% for all
      patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG
      group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and
      alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all
      patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In
      conclusion, the CY/rATG regimen seems to be associated with similar outcome
      results, but presented less toxicity when compared with the BEAM/hATG regimen.
      Long-term follow-up would be required to fully assess the differences in
      therapeutic effectiveness between the two regimens.

PMID- 19584828
TI  - The utility of capsule endoscopy in patients with suspected Crohn's disease.
AB  - OBJECTIVES: In patients with suspected Crohn's disease (CD), little is known
      about the test characteristics of capsule endoscopy (CE) in the diagnosis of this
      condition. We sought to determine the utility of CE for the subsequent diagnosis
      of CD in patients suspected to have this condition. METHODS: All patients who
      underwent CE at a single tertiary-care center for investigation of suspected
      small bowel CD, and who had a 12-month follow-up, were included in the study. All
      patients had undergone other investigations that were normal or equivocal. The
      test characteristics of CE were determined on the basis of capsule findings of
      small bowel ulcers and a subsequent new diagnosis of CD within 12 months of CE.
      RESULTS: The study included 102 patients with 12-month follow-up data. The
      majority (75%) met the established criteria to define "suspected Crohn's disease"
      as an indication for CE. Most had undergone computed tomography scan or small
      bowel follow-through (92%) and colonoscopy (99%) before CE. There were abnormal
      CE findings suggestive of CD in 39 patients. The prevalence rate of a new
      diagnosis of CD by 12 months in the study population was 13%. Using the presence
      of more than 3 ulcers as the criterion for an abnormal CE study, the sensitivity
      of CE for the diagnosis of CD was 77%, the specificity was 89%, the positive
      predictive value (PPV) was 50%, and the negative predictive value (NPV) was 96%.
      CONCLUSIONS: In patients with suspected CD, CE has a high sensitivity and a NPV
      for this condition. The PPV varies depending on the patient population and the
      criteria for a CE diagnosis of CD.

PMID- 19584829
TI  - High accuracy of narrow band imaging without magnification for the real-time
      characterization of polyp histology and its comparison with high-definition white
      light colonoscopy: a prospective study.
AB  - OBJECTIVES: Standard white light colonoscopy has limited ability to differentiate
      between polyp types (adenomatous vs. hyperplastic). Narrow band imaging (NBI)
      highlights the superficial mucosal/vascular patterns on polyps and may facilitate
      real-time characterization of polyp histology. The aim of this study was to
      prospectively evaluate and compare the diagnostic characteristics of high
      definition white light colonoscopy (HDWL) and NBI without magnification in the
      real-time prediction of polyp histology (adenomatous vs. hyperplastic) by
      evaluating the surface mucosal and vascular patterns. METHODS: We conducted a
      prospective comparative study in a tertiary referral center. A total of 100
      patients referred for screening or surveillance colonoscopy were prospectively
      enrolled and underwent colonoscopy using a high-definition colonoscope with NBI
      capability. Every polyp detected was initially evaluated with HDWL followed by
      NBI for the presence of surface mucosal/vascular patterns. Based on these
      patterns, polyp histology was predicted by both modalities. The main outcome
      measurements were: (i) diagnostic characteristics of HDWL and NBI in predicting
      polyp histology and (ii) impact of polyp size and learning effect (first half of
      study vs. second half) on the ability of NBI to predict adenomas. RESULTS: A
      total of 236 polyps were detected in 100 patients-143 adenomas, 77 hyperplastic,
      and 16 others. Surface patterns (type A: hyperplastic; type B: adenomatous) were
      recognized in all polyps with NBI (100%) compared to 45% with HDWL. For
      predicting adenomas, NBI had a significantly higher sensitivity and greater
      accuracy (96 and 93% respectively) compared with HDWL (38 and 61% respectively)
      (all P<0.0001). Although the accuracy of NBI for predicting adenomas improved
      with increasing polyp size (< or =5 mm; 6-9 mm; > or =10 mm) and in the second
      half compared with the first half of the study, these differences were not
      statistically significant. CONCLUSIONS: Using a simple surface mucosal/vascular
      pattern classification, NBI without magnification was highly accurate and
      significantly superior to HDWL for the real-time prediction of adenomas.

PMID- 19584830
TI  - A randomized clinical study evaluating the safety and efficacy of a new, reduced
      volume, oral sulfate colon-cleansing preparation for colonoscopy.
AB  - OBJECTIVES: We sought to evaluate a new, low-volume, oral sulfate solution as a
      bowel preparation for colonoscopy in adult patients. METHODS: The investigations
      were designed as two multicenter, single-blind, randomized, non-inferiority
      studies to show that the sulfate regimen would effect cleansing that is
      acceptable and equivalent to polyethylene glycol electrolyte solution with
      ascorbic acid (PEG-EA), and would be suitable for colonoscopy. One study
      evaluated same-day administration; the other compared the two study preparations
      given by split-dose administration in which the first portion was taken the
      evening before colonoscopy and the second portion on the morning of the
      procedure. The primary efficacy variable was based on bowel cleansing graded by
      an investigator who was unaware of the preparation method received. RESULTS:
      Study 1 randomized 408 outpatients scheduled for colonoscopy for routine
      indications, with 387 subjects taking the preparation. In all, 364 subjects were
      randomized and took the preparation in study 2. The demographics of the enrolled
      subjects were similar across both treatment groups in the two studies, including
      gender, race, and ethnic characteristics. The primary efficacy analysis supports
      the conclusion that the oral sulfate solution produces the same degree of
      cleansing as PEG-EA. Successful preparations were seen in 82.4% and 80.3% in
      study 1 and 97.2% and 95.6% in study 2 for the oral sulfate solution and the PEG
      EA regimen, respectively. Although no difference in excellent preparations was
      seen in the 1-day preparation, split-dose administration resulted in more
      excellent preparations in the sulfate group than in the PEG-EA group (63.3 vs.
      52.5%, P=0.043). Preparation-related symptoms of cramping, bloating, nausea, and
      vomiting were generally mild and infrequent. Sulfate subjects reported slightly
      increased gastrointestinal events and higher vomiting scores (P=0.009) in the 1
      day preparation but not in the split-dose regimen. There were no other
      differences for adverse events or clinically significant laboratory findings,
      including no increased creatinine. CONCLUSIONS: The new 960 -ml oral sulfate
      solution is effective for colonoscopy cleansing and has an acceptable safety
      profile.

PMID- 19584831
TI  - Early HBeAg loss during peginterferon alpha-2b therapy predicts HBsAg loss:
      results of a long-term follow-up study in chronic hepatitis B patients.
AB  - OBJECTIVES: Treatment with pegylated interferon (PEG-IFN) alpha-2b results in
      hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment.
      The aim of this study was to determine whether a long-term response to PEG-IFN is
      dependent on the timing of HBeAg loss. METHODS: A total of 91 patients treated
      with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with
      PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this
      study. Patients were initially followed up at 4-week intervals and had one
      additional long-term follow-up (LTFU) visit (mean: 3.03+/-0.77 years 26 weeks
      post treatment). RESULTS: Of the 172 patients included, 78 patients (46%) did not
      have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%)
      had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss< or =32 weeks
      had hepatitis B virus DNA of <400 copies/ml significantly more often than did
      those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis
      B surface antigen (HBsAg) negativity was also observed significantly more often
      in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg
      loss tended to occur more often in patients treated with PEG-IFN and lamivudine
      combination therapy than in those treated with PEG-IFN alone (35 vs. 21%;
      P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14). CONCLUSIONS: Early PEG-IFN
      induced HBeAg loss results in a high likelihood of HBsAg loss and may be
      associated with more profound viral suppression during the first 32 weeks of
      therapy in patients treated with lamivudine combinations.

PMID- 19584832
TI  - Immunomodulators are associated with a lower risk of first surgery among patients
      with non-penetrating non-stricturing Crohn's disease.
AB  - OBJECTIVES: Early immunomodulator therapy may alter the natural history of
      Crohn's disease in certain patients. We determined whether immunomodulator use
      was associated with a lower risk of first surgery among patients with non
      stricturing non-penetrating Crohn's disease. METHODS: A total of 159 consecutive
      patients with non-penetrating non-stricturing Crohn's disease from 1994 to 2005
      were retrospectively identified and followed from diagnosis to either first
      surgery (surgery group) or last clinic follow-up (medication group) in a
      historical cohort analysis. Immunomodulator use, duration, disease location, age
      at diagnosis, smoking, family history, and decade of diagnosis were compared. Cox
      proportional hazards models were adjusted for propensity score to determine
      whether immunomodulator use lasting >6 months decreased the risk of first surgery
      and whether duration of therapy affected risk. RESULTS: The median duration of
      follow-up was similar (6.0 vs. 5.5 years), age at diagnosis 10 years earlier, and
      isolated colonic disease three times less common (18 vs. 49%) in the surgery
      group as compared with the medication group. Immunomodulator use increased with
      time but overall was less common in the surgical group (24 vs. 48%). In the
      multivariate Cox proportional hazards model immunomodulator use was associated
      with a lower risk of surgery (hazard ratio, 0.41; 95% confidence interval 0.21
      0.81) after adjustment for propensity score. Similarly, risk of surgery declined
      with duration of use. CONCLUSIONS: Immunomodulator use is associated with a
      decreased risk of first surgery among patients with non-stricturing non
      penetrating CD. Early immunomodulator therapy may be beneficial in preventing
      first surgery in this population that has yet to develop penetrating or
      fistulizing complications.

PMID- 19584833
TI  - DNA promoter hypermethylation of p16 and APC predicts neoplastic progression in
      Barrett's esophagus.
AB  - OBJECTIVES: Prediction of progression to cancer in patients with Barrett's
      esophagus (BE) is difficult using current techniques. We determined whether DNA
      promoter hypermethylation of genes frequently methylated in esophageal
      adenocarcinoma (p16 and APC) could be used as predictors of progression in BE.
      METHODS: We first performed a cross-sectional study to evaluate the prevalence of
      gene hypermethylation in biopsies from patients with normal esophagus (n=17), BE
      (n=102), and adenocarcinoma (n=42). We then performed a nested case-control study
      comparing gene hypermethylation in BE patients who progressed from baseline
      pathology to high-grade dysplasia or cancer (n=7) vs. patients who did not
      progress (n=50). RESULTS: None of the patients with normal esophagus had p16 or
      APC hypermethylation. Hypermethylation was prevalent in BE without dysplasia or
      low-grade dysplasia (p16=31% and APC=50%; P<0.01) and high-grade dysplasia or
      adenocarcinoma (p16=54% and APC=68%; P<0.001) compared with normal esophagus (not
      detected). Patients who progressed from baseline pathology to high-grade
      dysplasia or cancer had higher prevalence of hypermethylation in their initial
      esophagus biopsies compared with those who did not progress for both p16 (100 vs.
      33%; P=0.008) and APC (86 vs. 40%; P=0.02). Hypermethylation of both p16 and APC
      was a strong predictor of subsequent progression to high-grade dysplasia or
      cancer during a mean follow-up time of 4.1 years (odds ratio (95% confidence
      interval)=14.97 (1.73,inf), P=0.01). Among patients who were negative for both
      p16 and APC hypermethylation, none progressed from baseline pathology to high
      grade dysplasia or cancer. CONCLUSIONS: Hypermethylation of both p16 and APC
      strongly predicts progression to high-grade dysplasia or cancer in patients with
      BE. Absence of p16 and APC hypermethylation is associated with a benign course.

PMID- 19584834
TI  - Appendicectomy as a therapy for ulcerative proctitis.
AB  - OBJECTIVES: Available data regarding whether appendicectomy performed after the
      onset of ulcerative colitis can modulate its clinical course are currently
      limited. This study aimed at addressing this issue. METHODS: In this study, we
      report a prospective case series of 30 adult patients (median age 35 years, range
      17-70 years; male/female: 11/19) with ulcerative proctitis (median duration of
      symptoms 5 years, range 8 months to 30 years; median Simple Clinical Colitis
      Activity Index score 9, range 7-12), who underwent appendicectomy in the absence
      of any history suggestive of previous appendicitis. Patients were subsequently
      followed up clinically with the assessment of the Simple Clinical Colitis
      Activity Index for a median of 14 months (range 9-32 months). RESULTS: After
      appendicectomy, the clinical activity index improved significantly to a median
      score of 2 (range 0-12) (P<0.0005). The improvement in the clinical activity
      index occurred in 27 of 30 (90%) patients, whereas the index remained unchanged
      in the remaining 3 of 30 (10%) patients. Furthermore, 12 of 30 (40%) patients
      experienced a complete resolution of symptoms (clinical activity index score of
      0) by 12 months, such that all pharmacological treatments could be withdrawn, and
      have remained in remission off all previous treatments for a median 9 months
      (range 6-25 months). The time required for a complete resolution of symptoms post
      appendicectomy ranged from 1 to 12 months (median 3 months) (Kaplan-Meier
      analysis). None of the clinical or histological factors analyzed were
      significantly associated with post-appendicectomy outcome. CONCLUSIONS: This case
      series, the largest reported so far, provides rationale for controlled trials to
      properly evaluate the possible role of appendicectomy in the treatment of
      ulcerative proctitis.

PMID- 19584836
TI  - Elucidating regulatory mechanisms downstream of a signaling pathway using
      informative experiments.
AB  - Signaling cascades are triggered by environmental stimulation and propagate the
      signal to regulate transcription. Systematic reconstruction of the underlying
      regulatory mechanisms requires pathway-targeted, informative experimental data.
      However, practical experimental design approaches are still in their infancy.
      Here, we propose a framework that iterates design of experiments and
      identification of regulatory relationships downstream of a given pathway. The
      experimental design component, called MEED, aims to minimize the amount of
      laboratory effort required in this process. To avoid ambiguity in the
      identification of regulatory relationships, the choice of experiments maximizes
      diversity between expression profiles of genes regulated through different
      mechanisms. The framework takes advantage of expert knowledge about the pathways
      under study, formalized in a predictive logical model. By considering model
      predicted dependencies between experiments, MEED is able to suggest a whole set
      of experiments that can be carried out simultaneously. Our framework was applied
      to investigate interconnected signaling pathways in yeast. In comparison with
      other approaches, MEED suggested the most informative experiments for unambiguous
      identification of transcriptional regulation in this system.

PMID- 19584837
TI  - The insider's guide to plagiarism.

PMID- 19584838
TI  - Conflict of interest rules seen by some as too stringent.

PMID- 19584835
TI  - Optimal tuning of bacterial sensing potential.
AB  - Through production and sensing of small signal molecules, quorum sensing (QS)
      enables bacteria to detect changes in their density and regulate their functions
      accordingly. QS systems are tremendously diverse in terms of their specific
      sensory components, the biochemical and transport properties of signaling
      molecules, their target functions and the context in which QS-mediated functions
      are activated. Cutting across this diversity, however, the central architecture
      of QS systems is universal; it comprises signal synthesis, secretion, degradation
      and detection. We are thus able to derive a general metric for QS 'sensing
      potential' based on this 'core' module. The sensing potential quantifies the
      ability of a single bacterium to sense the dimensions of its microenvironment.
      This simple metric captures the dominant activation properties of diverse QS
      systems, giving a concise description of the sensing characteristics. As such, it
      provides a convenient quantitative framework to study the phenotypic effects of
      QS characteristics. As an example, we show how QS characteristics uniquely
      determine the scenarios in which regulation of a typical QS-controlled function,
      such as exoenzyme secretion, becomes advantageous.

PMID- 19584839
TI  - A close look at acid reflux drugs points to possible risks.

PMID- 19584841
TI  - Report details changes and challenges for women in biomedicine.

PMID- 19584843
TI  - New initiative launched to support research in Africa.

PMID- 19584844
TI  - Nuclear watchdog and WHO move forward against cancer.

PMID- 19584845
TI  - High-tech bandages lighten the load of light therapy.

PMID- 19584847
TI  - Straight talk with... Mauro Ferrari. Interviewed by Jon Evans.

PMID- 19584848
TI  - Outpacing cancer.

PMID- 19584854
TI  - Antibody affinity maturation and respiratory syncytial virus disease.

PMID- 19584855
TI  - Will integrin inhibitors have proangiogenic effects in the clinic?

PMID- 19584857
TI  - Receptors identified for hand, foot and mouth virus.

PMID- 19584858
TI  - Coupling bone degradation to formation.

PMID- 19584859
TI  - Tumor immunotherapy: making an immortal army.

PMID- 19584860
TI  - Targeting lymphotoxin depletes pathogenic T cells.

PMID- 19584862
TI  - Damage control in the nervous system: rehabilitation in a plastic environment.

PMID- 19584863
TI  - Damage control in the nervous system: beware the immune system in spinal cord
      injury.

PMID- 19584865
TI  - Alefacept promotes co-stimulation blockade based allograft survival in nonhuman
      primates.
AB  - Memory T cells promote allograft rejection particularly in co-stimulation
      blockade-based immunosuppressive regimens. Here we show that the CD2-specific
      fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig)
      selectively eliminates memory T cells and, when combined with a co-stimulation
      blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80
      and CD86-specific fusion protein, prevents renal allograft rejection and
      alloantibody formation in nonhuman primates. These results support the immediate
      translation of a regimen for the prevention of allograft rejection without the
      use of calcineurin inhibitors, steroids or pan-T cell depletion.

PMID- 19584866
TI  - A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA
      helicase A inhibits growth of Ewing's sarcoma.
AB  - Many sarcomas and leukemias carry nonrandom chromosomal translocations encoding
      tumor-specific mutant fusion transcription factors that are essential to their
      molecular pathogenesis. Ewing's sarcoma family tumors (ESFTs) contain a
      characteristic t(11;22) translocation leading to expression of the oncogenic
      fusion protein EWS-FLI1. EWS-FLI1 is a disordered protein that precludes standard
      structure-based small-molecule inhibitor design. EWS-FLI1 binding to RNA helicase
      A (RHA) is important for its oncogenic function. We therefore used surface
      plasmon resonance screening to identify compounds that bind EWS-FLI1 and might
      block its interaction with RHA. YK-4-279, a derivative of the lead compound from
      the screen, blocks RHA binding to EWS-FLI1, induces apoptosis in ESFT cells and
      reduces the growth of ESFT orthotopic xenografts. These findings provide proof of
      principle that inhibiting the interaction of mutant cancer-specific transcription
      factors with the normal cellular binding partners required for their oncogenic
      activity provides a promising strategy for the development of uniquely effective,
      tumor-specific anticancer agents.

PMID- 19584870
TI  - Do we need biopsies of metastases for colorectal cancer patients?

PMID- 19584867
TI  - TGF-beta1-induced migration of bone mesenchymal stem cells couples bone
      resorption with formation.
AB  - Bone remodeling depends on the precise coordination of bone resorption and
      subsequent bone formation. Disturbances of this process are associated with
      skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in
      vitro and in vivo models that active TGF-beta1 released during bone resorption
      coordinates bone formation by inducing migration of bone marrow stromal cells,
      also known as bone mesenchymal stem cells, to the bone resorptive sites and that
      this process is mediated through a SMAD signaling pathway. Analyzing mice
      carrying a CED-derived mutant TGFB1 (encoding TGF-beta1), which show the typical
      progressive diaphyseal dysplasia seen in the human disease, we found high levels
      of active TGF-beta1 in the bone marrow. Treatment with a TGF-beta type I receptor
      inhibitor partially rescued the uncoupled bone remodeling and prevented the
      fractures. Thus, as TGF-beta1 functions to couple bone resorption and formation,
      modulation of TGF-beta1 activity could be an effective treatment for bone
      remodeling diseases.

PMID- 19584874
TI  - Five reasons to distrust the trust model.

PMID- 19584872
TI  - All-oral combination of oral vinorelbine and capecitabine as first-line
      chemotherapy in HER2-negative metastatic breast cancer: an International Phase II
      Trial.
AB  - BACKGROUND: This multicentre, international phase II trial evaluated the efficacy
      and safety profile of a first-line combination of oral vinorelbine plus
      capecitabine for women with metastatic breast cancer (MBC). METHODS: Patients
      with measurable, HER2-negative disease received, as a first line in metastatic
      setting, 3-weekly cycles of oral vinorelbine 80 mg m(-2) (after a first cycle at
      60) on day 1 and day 8, plus capecitabine 1000 mg m(-2) (750 if >or=65 years of
      age) twice daily, on days 1-14. Treatment was continued until progression or
      unacceptable toxicity. RESULTS: A total of 55 patients were enrolled and 54 were
      treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had
      received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST)
      in 49 evaluable patients was 51% (95% confidence interval (CI), 36-66), including
      complete response in 4%. The clinical benefit rate (response or stable disease
      for >or=6 months) was 63% (95% CI, 48-77). The median duration of response was
      7.2 months (95% CI, 6.4-10.2). After a median follow-up of 41 months, median
      progression-free survival was 8.4 months (95% CI, 5.8-9.7) and median overall
      survival was 29.2 months (95% CI, 18.2-40.1). Treatment-related adverse events
      were manageable, the main grade 3-4 toxicity was neutropaenia (49%); two patients
      experienced febrile neutropaenia and three patients had a neutropaenic infection
      (including one septic death). A particularly low rate of alopaecia was observed.
      CONCLUSION: These results show that the all-oral combination of oral vinorelbine
      and capecitabine is an effective and well-tolerated first-line regimen for MBC.

PMID- 19584875
TI  - Colon cancer screening consultations can aid in obesity management.

PMID- 19584876
TI  - Retraction: Update to "C-reactive protein and metabolic syndrome in youth: a
      strong relationship?".

PMID- 19584877
TI  - Two-year follow-up in 21,784 overweight children and adolescents with lifestyle
      intervention.
AB  - Although randomized controlled trials demonstrated the long-term efficacy of
      lifestyle interventions in overweight children, the effects of these
      interventions in clinical practice under real-life conditions are largely
      unknown. One hundred twenty-nine centers specialized in outpatient pediatric
      obesity care participated in this quality assessment. All patients presenting
      before the year 2006 for lifestyle intervention of at least 6 months duration in
      these institutions were analyzed in a 2-year follow-up. A total of 21,784 (45%
      male) overweight children and adolescents aged 2-20 years (mean BMI 30.4 kg/m2,
      mean SDS-BMI 2.51, mean age 12.6 years) were included in the analysis. Based on
      an intention-to-treat analysis with variables set back to baseline in lost of
      follow-up, 22% of the children reduced their SDS-BMI after 6 months, 15% after 12
      months, and 7% after 24 months, but only in 24, 17, and 8% of children,
      respectively, complete data were available. In the five treatment centers with
      the best outcome (518 patients), 83% of the children reduced their overweight
      after 6 months, 67% after 12 months, and 51% after 24 months. Under real-life
      conditions, most treatment centers cannot prove the long-term efficacy of their
      interventions due to high drop-out rate or lack of documentation. Conversely,
      some institutions achieved a reduction of overweight in nearly the half of their
      patients 24 months after baseline demonstrating the great heterogeneity in
      outcome. To improve the effectiveness of lifestyle interventions in real-life
      studying, the process and structure quality as well as their long-term results is
      urgently needed.

PMID- 19584878
TI  - Metabolic implications of dietary trans-fatty acids.
AB  - Dietary trans-fatty acids are associated with increased risk of cardiovascular
      disease and have been implicated in the incidence of obesity and type 2 diabetes
      mellitus (T2DM). It is established that high-fat saturated diets, relative to low
      fat diets, induce adiposity and whole-body insulin resistance. Here, we test the
      hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat
      accumulation, insulin resistance) are also worsened with provision of a low-fat
      diet containing elaidic acid (18:1t), the predominant trans-fatty acid isomer
      found in the human food supply. Male 8-week-old Sprague-Dawley rats were fed a
      10% trans-fatty acid enriched (LF-trans) diet for 8 weeks. At baseline, 3 and 6
      weeks, in vivo magnetic resonance spectroscopy (1H-MR) assessed intramyocellular
      lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic-hyperinsulinemic
      clamps (week 8) determined whole-body and tissue-specific insulin sensitivity
      followed by high-resolution ex vivo 1H-NMR to assess tissue biochemistry. Rats
      fed the LF-trans diet were in positive energy balance, largely explained by
      increased energy intake, and showed significantly increased visceral fat and
      liver lipid accumulation relative to the low-fat control diet. Net glycogen
      synthesis was also increased in the LF-trans group. A reduction in glucose
      disposal, independent of IMCL accumulation was observed in rats fed the LF-trans
      diet, whereas in rats fed a 45% saturated fat (HF-sat) diet, impaired glucose
      disposal corresponded to increased IMCLTA. Neither diet induced an increase in
      IMCLsoleus. These findings imply that trans-fatty acids may alter nutrient
      handling in liver, adipose tissue, and skeletal muscle and that the mechanism by
      which trans-fatty acids induce insulin resistance differs from diets enriched
      with saturated fats.

PMID- 19584879
TI  - HDL subspecies in young adult twins: heritability and impact of overweight.
AB  - The association between abdominal obesity and atherogenic lipid profile emerges
      from complex interactions of genes and environment. We aimed to explore the
      heritability and effects of overweight on serum lipid profile (high-density
      lipoprotein-cholesterol (HDL-C), HDL mean particle size, percentages of HDL(2b,
      2a, 3a, 3b, and 3c,) low-density lipoprotein-cholesterol (LDL-C), LDL peak
      particle size and triglycerides (TGs)) in healthy, young adults. HDL-C, LDL-C,
      and TG were measured in 52 monozygotic (MZ) and 89 dizygotic (DZ) twin pairs,
      aged 23-32 years, chosen to represent a wide range of BMIs (17.6-42.9 kg/m2). Of
      them, 24 MZ and 26 DZ pairs were chosen at random for measurements of HDL mean
      and LDL peak particle sizes and percentages of HDL subspecies. The heritabilities
      of the lipid parameters adjusted for BMI were HDL-C 73%, HDL mean particle size
      56%, HDL subspecies 46-63%, LDL-C 79%, LDL peak particle size 49%, and TG 64%.
      Genetic and environmental correlations between BMI and HDL-C, LDL-C, and TG were
      modest (0.3-0.4). Abdominal overweight (waist circumference>or=94 cm for males
      and >or=80 cm for females) associated with decreased HDL-C, increased LDL-C, and
      TG concentrations, smaller HDL mean particle size, lower HDL2b, and higher HDL3c
      percentages in both genders. Within MZ twins, controlling for genetic influences,
      within-pair differences in HDL3c percentage were associated with those in waist
      (r=0.46, P=0.032) and BMI (r=0.51, P=0.013). In conclusion, serum lipid
      parameters, including LDL peak and HDL mean particle sizes and HDL subspecies
      distribution are under strong genetic control. Overweight associated with
      significant lipid profile changes, particularly, small HDL3c increased in
      overweight independent of genetic influences.

PMID- 19584880
TI  - Genes on rat chromosomes 3, 5, 10, and 16 are linked with facets of metabolic
      syndrome.
AB  - WOKW (Wistar Ottawa Karlsburg W) rats develop metabolic syndrome closely
      resembling human disorder. In crossing studies between disease-prone WOKW and
      disease-resistant DA (Dark Agouti) rats, several quantitative trait loci (QTLs)
      were mapped. To prove the in vivo relevance of QTLs, congenic DA.WOKW rats,
      briefly termed DA.3aW, DA.3bW, DA.5W, DA.10W, and DA.16W, were generated by
      transferring chromosomal regions of WOKW chromosomes 3, 5, 10, and 16 onto DA
      genetic background. Male (n=12) and female (n=12) rats of each congenic strain
      and their parental strain DA were characterized for adiposity index (AI), serum
      leptin, and serum insulin as well as serum cholesterol and serum triglycerides as
      single facets of metabolic syndrome at the age of 30 weeks. The data showed a
      significant higher AI for male and female DA.3aW and female DA.16W compared with
      DA. Serum leptin was significantly elevated in male and female DA.3aW, DA.10W,
      and DA.16W rats in comparison with DA. Rats of both sexes of DA.10W and female
      DA.16W showed significantly elevated serum insulin in comparison to DA. Female
      rats of all congenics had significantly higher serum cholesterol compared with
      DA, while males did not differ. Finally, triglycerides were only elevated in male
      DA.16W. The results demonstrate an involvement of WOKW chromosomes 3, 5, 10, and
      16 in developing facets of the metabolic syndrome.

PMID- 19584881
TI  - Admixture mapping of quantitative trait loci for BMI in African Americans:
      evidence for loci on chromosomes 3q, 5q, and 15q.
AB  - Obesity is a heritable trait and a major risk factor for highly prevalent common
      diseases such as hypertension and type 2 diabetes. Previously we showed that BMI
      was positively correlated with African ancestry among the African Americans (AAs)
      in the US National Heart, Lung, and Blood Institute's Family Blood Pressure
      Program (FBPP). In a set of 1,344 unrelated AAs, using Individual Ancestry (IA)
      estimates at 284 marker locations across the genome, we now present a
      quantitative admixture mapping analysis of BMI. We used a set of unrelated
      individuals from Nigeria to represent the African ancestral population and the
      European American (EA) in the FBPP as the European ancestral population. The
      analysis was based on a common set of 284 microsatellite markers genotyped in all
      three groups. We considered the quantitative trait, BMI, as the response variable
      in a regression analysis with the marker location specific excess European
      ancestry as the explanatory variable. After suitably adjusting for different
      covariates such as sex, age, and network, we found strong evidence for a positive
      association with European ancestry at chromosome locations 3q29 and 5q14 and a
      negative association on chromosome 15q26. To our knowledge, this is the largest
      quantitative admixture mapping effort in terms of sample size and marker locus
      involvement for the trait. These results suggest that these regions may harbor
      genes influencing BMI in the AA population.

PMID- 19584884
TI  - Youth BMI trajectories: evidence from the NLSY97.
AB  - We examined heterogeneity in BMI trajectory classes among youth and variables
      that may be associated with trajectory class membership. We used data from seven
      rounds (1997-2003) of the 1997 National Longitudinal Survey of Youth (NLSY97), a
      nationally representative, longitudinal survey of people born between 1980 and
      1984 who were living in the United States in 1997. The analyses were based on an
      accelerated longitudinal design. General growth mixture modeling implemented in
      Mplus (version 4.1) was used to identify subtypes of youth BMI growth
      trajectories over time. Four distinct youth BMI trajectories were identified.
      Class 1 includes youth at high risk for becoming obese by young adulthood (at age
      12 and 23, approximately 67 and 90%, respectively, are classified as obese, and
      almost 72% will have had a BMI>or=40 at some time during this developmental
      period). Class 2 includes youth at moderate-to-high risk (at age 12 and 23,
      approximately 55 and 68%, respectively, are classified as obese). Class 3
      includes youth at low-to-moderate risk (i.e., at age 12 and 23, approximately 8
      and 27%, respectively, are classified as obese). Class 4 includes youth at low
      risk (few of these youth are obese at any age during this developmental period).
      These results highlight the importance of considering heterogeneity in BMI growth
      among youth and early interventions among those most at risk of the adverse
      health consequences of excess weight.

PMID- 19584883
TI  - Visceral and subcutaneous adiposity and adiponectin in middle-aged Japanese men:
      the ERA JUMP study.
AB  - Adiponectin is reduced in obesity and has been suggested to play an important
      role in modulation of atherosclerosis. We studied the relationship between
      visceral (VAT) and subcutaneous (SAT) adipose tissue and serum adiponectin
      concentrations in Japanese men. Participants were 304 randomly selected community
      based Japanese men aged 40-49 without a prior history of cardiovascular disease.
      Participants were grouped according to tertiles of serum adiponectin. In multiple
      linear regression analysis including age, pack years of smoking, and alcohol
      intake as covariates, log-transformed adiponectin was inversely associated with
      both VAT and SAT when these two obesity measures were included separately in the
      models. However, log-transformed adiponectin was inversely associated with VAT
      (standardized beta estimate=-0.465; P<0.0001) and positively associated with SAT
      (standardized beta estimate=1.277; P=0.03), when these were included
      concomitantly in the model. In conclusion, VAT and SAT had differential
      associations with serum adiponectin concentrations.

PMID- 19584882
TI  - Correlates and heritability of nonalcoholic fatty liver disease in a minority
      cohort.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin
      resistance. The condition disproportionately affects Hispanic Americans. The aims
      of this study were to examine the risk factors and heritability of NAFLD in 795
      Hispanic American and 347 African-American adults participating in the Insulin
      Resistance Atherosclerosis Study (IRAS) Family Study. Computed tomography (CT)
      scans of the abdomen were evaluated centrally for measures of liver-spleen (LS)
      density ratio and abdominal fat distribution. Other measures included insulin
      sensitivity (SI) calculated from a frequently sampled intravenous glucose
      tolerance test and various laboratory measures. Statistical models which adjust
      for familial relationships were estimated separately for the two ethnic groups.
      Heritability was calculated using a variance components approach. The mean age of
      the cohort was 49 years (range 22-84); 66% were female. NAFLD (LS ratio<1) was
      more common in Hispanic Americans (24%) than African Americans (10%). NAFLD was
      independently associated with SI and visceral adipose tissue (VAT) area in both
      ethnic groups, although the proportion of explained variance was considerably
      higher in the Hispanic models. Adiponectin contributed significantly in the
      African-American models whereas triglycerides (TGs) and plasminogen activator
      inhibitor 1 (PAI-1) contributed only in the Hispanic models. Liver density was
      modestly heritable in both ethnic groups (h2 approximately 0.35). In summary, the
      prevalence of NAFLD was twofold greater in Hispanic than African Americans.
      Certain correlates of NAFLD were similar between the ethnic groups, whereas
      others were distinct. NAFLD was modestly heritable. These findings suggest that
      NAFLD may have a differing environmental and/or genetic basis in these ethnic
      groups.

PMID- 19584885
TI  - Body composition measured by dual-energy X-ray absorptiometry half-body scans in
      obese adults.
AB  - Dual-energy X-ray absorptiometry (DXA) has become a common measurement of human
      body composition. However, obese subjects have been understudied largely due to
      weight and scan area restrictions. Newer DXA instruments allow for heavier
      subjects to be supported by the DXA scanner, but the imaging area is still
      smaller than the body size of some obese subjects. In this study, we determined
      the validity of an automated half-scan methodology by comparing to the standard
      whole-body scans in a cohort of obese volunteers. Fifty-two subjects whose BMI>30
      kg/m2 completed whole-body iDXA (GE Lunar) scans. The resulting scans were
      analyzed in three ways: the standard whole-body scan, total body estimated from
      the left side, and from the right side. Fat mass, nonbone lean mass, bone mineral
      content (BMC), and percent fat derived from each half scan were compared to the
      whole-body scans. Total fat mass, nonbone lean mass, or percent fat was
      comparable for the whole-body scans, left, and right side scans (>97% within
      individuals and >99.9% for the group). The BMC estimate using the right side scan
      was slightly but statistically higher than the whole-body BMC (approximately 30 g
      or 1%, P<0.001), while the left side scan BMC estimate was lower than the whole
      body BMC by the same magnitude. No significant magnitude bias was found for any
      of the composition variables. We conclude that the new iDXA half-body analysis in
      obese subjects appears to be closely comparable to whole-body analysis for fat
      mass, nonbone lean mass, and percent fat.

PMID- 19584886
TI  - TNF-alpha promoter methylation as a predictive biomarker for weight-loss
      response.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine which is
      commonly elevated in obese subjects and whose promoter is susceptible to be
      regulated by cytosine methylation. The aim of this research was to analyze
      whether epigenetic regulation of human TNF-alpha promoter by cytosine methylation
      could be involved in the predisposition to lose body weight after following a
      balanced hypocaloric diet. Twenty-four patients (12 women/12 men) with excessive
      body weight-for-height (BMI: 30.5+/-0.32 kg/m2; age: 34+/-4 years old) followed
      an 8-week energy-restricted diet. Blood mononuclear cell DNA, isolated before the
      nutritional intervention, was treated with bisulfite and a region of TNF-alpha
      gene promoter (from -360 to +50 bp) was sequenced. Obese men with successful
      weight loss (>or=5% of initial body weight) showed lower levels of total TNF
      alpha promoter methylation (r=0.74; P=0.021), especially in the positions -170 bp
      (r=0.75, P=0.005) and -120 bp (r=0.70, P=0.011). Baseline TNF-alpha circulating
      levels were positively associated with total promoter methylation (r=0.84,
      P=0.005) and methylation at position -245 bp (r=0.75, P=0.020). TNF-alpha
      promoter methylation could be a good inflammation marker predicting the
      hypocaloric diet-induced weight-loss, and constitutes a first step toward
      personalized nutrition based on epigenetic criteria.

PMID- 19584889
TI  - Association between regional cerebral blood flow during hypoglycemia and genetic
      and phenotypic traits of the renin-angiotensin system.
AB  - The risk of severe hypoglycemia in patients with type I diabetes and high basal
      activity in the renin-angiotensin system (RAS) is significantly higher than in
      patients with low basal RAS activity. In healthy men, we tested the hypothesis
      that differences in spontaneous RAS activity are associated with differences in
      cerebral activity responses during mild hypoglycemia. A total of 10 healthy men
      with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O
      PET (H(2)(15)O-positron emission tomography) study was conducted with a series of
      six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after
      hypoglycemia. The mean plasma glucose concentration was similar in both the
      groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.:
      0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral
      activity in the frontal area and a higher cerebral activity in the entorhinal
      area that expanded to include the parahippocampal gyrus after hypoglycemia. Our
      findings suggest that the high RAS group to a lesser extent than the low RAS
      group activates areas involving executive function that may explain the
      correlation between high basal RAS activity and risk of severe hypoglycemia in
      type I diabetes.

PMID- 19584890
TI  - Comparison of eight methods for the estimation of the image-derived input
      function in dynamic [(18)F]-FDG PET human brain studies.
AB  - The aim of this study was to compare eight methods for the estimation of the
      image-derived input function (IDIF) in [(18)F]-FDG positron emission tomography
      (PET) dynamic brain studies. The methods were tested on two digital phantoms and
      on four healthy volunteers. Image-derived input functions obtained with each
      method were compared with the reference input functions, that is, the activity in
      the carotid labels of the phantoms and arterial blood samples for the volunteers,
      in terms of visual inspection, areas under the curve, cerebral metabolic rates of
      glucose (CMRglc), and individual rate constants. Blood-sample-free methods
      provided less reliable results as compared with those obtained using the methods
      that require the use of blood samples. For some of the blood-sample-free methods,
      CMRglc estimations considerably improved when the IDIF was calibrated with a
      single blood sample. Only one of the methods tested in this study, and only in
      phantom studies, allowed a reliable calculation of the individual rate constants.
      For the estimation of CMRglc values using an IDIF in [(18)F]-FDG PET brain
      studies, a reliable absolute blood-sample-free procedure is not available yet.

PMID- 19584891
TI  - Characterization of tumor angiogenesis in rat brain using iron-based vessel size
      index MRI in combination with gadolinium-based dynamic contrast-enhanced MRI.
AB  - This study aimed at combining an iron-based, steady-state, vessel size index
      magnetic resonance imaging (VSI MRI) approach, and a gadolinium (Gd)-based,
      dynamic contrast-enhanced MRI approach (DCE MRI) to characterize tumoral
      microvasculature. Rats bearing an orthotopic glioma (C6, n=14 and RG2, n=6)
      underwent DCE MRI and combined VSI and DCE MRI 4 h later, at 2.35 T. Gd-DOTA (200
      mumol of Gd per kg) and ultrasmall superparamagnetic iron oxide (USPIO) (200
      micromol of iron per kg) were used for DCE and VSI MRI, respectively. C6 and RG2
      gliomas were equally permeable to Gd-DOTA but presented different blood volume
      fractions and VSI, in good agreement with histologic data. The presence of USPIO
      yielded reduced K(trans) values. The K(trans) values obtained with Gd-DOTA in the
      absence and in the presence of USPIO were well correlated for the C6 glioma but
      not for the RG2 glioma. It was also observed that, within the time frame of DCE
      MRI, USPIO remained intravascular in the C6 glioma whereas it extravasated in the
      RG2 glioma. In conclusion, VSI and DCE MRI can be combined provided that USPIO
      does not extravasate with the time frame of the DCE MRI experiment. The
      mechanisms at the origin of USPIO extravasation remain to be elucidated.

PMID- 19584892
TI  - Reduced ADAMTS13 activity in delayed cerebral ischemia after aneurysmal
      subarachnoid hemorrhage.
AB  - The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid
      hemorrhage (SAH) remains unknown. Besides vasospasm, microthrombosis might have
      an important function. As in patients with thrombotic thrombocytopenic purpura an
      A Disintegrin And Metalloprotease with ThromboSpondin repeats-13 (ADAMTS13)
      deficiency leads to higher concentrations of large von Willebrand factor (vWF)
      multimers resulting in microthrombosis, our purpose was to compare ADAMTS13 and
      vWF in patients with and without DCI after aneurysmal SAH. We measured ADAMTS13
      activity, vWF antigen, vWF propeptide, and vWF ristocetin cofactor activity in
      plasma at standard intervals. Thirty-one patients were included. Eleven patients
      (35%) developed DCI. No differences were observed in baseline characteristics
      between patients with and without DCI. Patients with DCI had a stronger decrease
      in ADAMTS13 activity, and a more profound increase in vWF antigen, vWF
      propeptide, and vWF activity in the first few days after the hemorrhage (P-values
      for difference in polynomial time trend 0.0001, 0.020, 0.004, and 0.188,
      respectively). No indication of correlation between vWF antigen and ADAMTS13 was
      found (r=-0.027, P=0.736). Our results suggest that microthrombosis has a role in
      the pathogenesis of DCI, as a result of decreased ADAMTS13 activity and
      endothelium dysfunction.

PMID- 19584894
TI  - How the olfactory bulb got its glomeruli: a just so story?
AB  - The nearly 2,000 glomeruli that cover the surface of the olfactory bulb are so
      distinctive that they were noted specifically in the earliest of Cajal's
      catalogues. They have variously been considered a functional unit, an
      organizational unit and a crucial component of the olfactory coding circuit.
      Despite their central position in olfactory processing, the development of the
      glomeruli has only recently begun to be investigated with new and powerful
      genetic tools. Some unexpected findings have been made that may lead to a new
      understanding of the processes involved in wiring sensory regions of the brain.
      It may no longer be sufficient to simply invoke genes, spikes and their interplay
      in the construction of brain circuits. The story of 'how the olfactory bulb got
      its glomeruli' may be more complex, and more revealing, than has been supposed.

PMID- 19584895
TI  - Bioavailability of alpha-linolenic acid from flaxseed diets as a function of the
      age of the subject.
AB  - BACKGROUND: Dietary flaxseed may have beneficial cardiovascular effects. An aged
      population has a higher incidence of cardiovascular disease, but they may react
      differently to flaxseed in the diet. OBJECTIVE: To investigate the response, over
      a period of 4 weeks, of subjects aged 18-29 or 45-69 years to a diet containing
      the same amount of alpha-linolenic acid (ALA) (6 g) introduced in the form of
      ground flaxseed (30 g) or flaxseed oil. RESULTS: All subjects who received
      flaxseed oil showed a significant increase in plasma ALA and eicosapentaenoic
      acid (EPA) concentrations over the course of this study. Subjects who received
      ground flaxseed in the 18-29-year-old group showed a statistically significant
      increase in their plasma ALA levels, and although there was a trend in the same
      direction for the 45-69-year-old subjects, this did not achieve statistical
      significance. The diets induced no major changes in platelet aggregation, plasma
      total cholesterol, low-density lipoprotein or high-density lipoprotein
      cholesterol levels in any of the groups. Younger subjects showed a decrease in
      triglyceride (TG) values compared with older subjects. There were no significant
      side effects that caused compliancy issues. CONCLUSION: Subject age does not seem
      to be a major determining factor in influencing ALA absorption from a flaxseed
      supplemented diet nor in the metabolism of ALA to EPA in the groups fed flaxseed
      oil. Concerns about side effects in older subjects administered a higher fiber
      load in a flaxseed-supplemented diet are not justified. However, younger but not
      older subjects showed a beneficial decrease in circulating TGs due to flaxseed
      supplementation.

PMID- 19584896
TI  - Legacy of mutiny on the Bounty: founder effect and admixture on Norfolk Island.
AB  - The population of Norfolk Island, located off the eastern coast of Australia,
      possesses an unusual and fascinating history. Most present-day islanders are
      related to a small number of the 'Bounty' mutineer founders. These founders
      consisted of Caucasian males and Polynesian females and led to an admixed present
      day population. By examining a single large pedigree of 5742 individuals,
      spanning >200 years, we analyzed the influence of admixture and founder effect on
      various cardiovascular disease (CVD)-related traits. On account of the relative
      isolation of the population, on average one-third of the genomes of present-day
      islanders (single large pedigree individuals) is derived from 17 initial
      founders. The proportion of Polynesian ancestry in the present-day individuals
      was found to significantly influence total triglycerides, body mass index,
      systolic blood pressure and diastolic blood pressure. For various cholesterol
      traits, the influence of ancestry was less marked but overall the direction of
      effect for all CVD-related traits was consistent with Polynesian ancestry
      conferring greater CVD risk. Marker-derived homozygosity was computed and agreed
      with measures of inbreeding derived from pedigree information. Founder effect
      (inbreeding and marker-derived homozygosity) significantly influenced height. In
      conclusion, both founder effect and extreme admixture have substantially
      influenced the genetic architecture of a variety of CVD-related traits in this
      population.

PMID- 19584893
TI  - Spinal muscular atrophy: why do low levels of survival motor neuron protein make
      motor neurons sick?
AB  - Many neurogenetic disorders are caused by the mutation of ubiquitously expressed
      genes. One such disorder, spinal muscular atrophy, is caused by loss or mutation
      of the survival motor neuron1 gene (SMN1), leading to reduced SMN protein levels
      and a selective dysfunction of motor neurons. SMN, together with partner
      proteins, functions in the assembly of small nuclear ribonucleoproteins (snRNPs),
      which are important for pre-mRNA splicing. It has also been suggested that SMN
      might function in the assembly of other ribonucleoprotein complexes. Two
      hypotheses have been proposed to explain the molecular dysfunction that gives
      rise to spinal muscular atrophy (SMA) and its specificity to a particular group
      of neurons. The first hypothesis states that the loss of SMN's well-known
      function in snRNP assembly causes an alteration in the splicing of a specific
      gene (or genes). The second hypothesis proposes that SMN is crucial for the
      transport of mRNA in neurons and that disruption of this function results in SMA.

PMID- 19584897
TI  - Caveolinopathies: from the biology of caveolin-3 to human diseases.
AB  - In muscle tissue the protein caveolin-3 forms caveolae--flask-shaped
      invaginations localized on the cytoplasmic surface of the sarcolemmal membrane.
      Caveolae have a key role in the maintenance of plasma membrane integrity and in
      the processes of vesicular trafficking and signal transduction. Mutations in the
      caveolin-3 gene lead to skeletal muscle pathology through multiple pathogenetic
      mechanisms. Indeed, caveolin-3 deficiency is associated to sarcolemmal membrane
      alterations, disorganization of skeletal muscle T-tubule network and disruption
      of distinct cell-signaling pathways. To date, there have been 30 caveolin-3
      mutations identified in the human population. Caveolin-3 defects lead to four
      distinct skeletal muscle disease phenotypes: limb girdle muscular dystrophy,
      rippling muscle disease, distal myopathy, and hyperCKemia. In addition, one
      caveolin-3 mutant has been described in a case of hypertrophic cardiomyopathy.
      Many patients show an overlap of these symptoms and the same mutation can be
      linked to different clinical phenotypes. This variability can be related to
      additional genetic or environmental factors. This review will address caveolin-3
      biological functions in muscle cells and will describe the muscle and heart
      disease phenotypes associated with caveolin-3 mutations.

PMID- 19584898
TI  - Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile
      men.
AB  - DNA methylation marks, a key modification of imprinting, are erased in primordial
      germ cells and sex specifically re-established during gametogenesis. Abnormal
      epigenetic programming has been proposed as a possible mechanism compromising
      male fertility. We analysed by pyrosequencing the DNA methylation status of 47
      CpGs located in differentially methylated regions (DMRs), the DMR0 and DMR2 of
      the IGF2 gene and in the 3rd and 6th CTCF-binding sites of the H19 DMR in human
      sperm from men with normal semen and patients with teratozoospermia (T) and/or
      oligo-astheno-teratozoospermia (OAT). All normal semen samples presented the
      expected high global methylation level for all CpGs analysed. In the
      teratozoospermia group, 11 of 19 patients presented a loss of methylation at
      variable CpG positions either in the IGF2 DMR2 or in both the IGF2 DMR2 and the
      6th CTCF of the H19 DMR. In the OAT group, 16 of 22 patients presented a severe
      loss of methylation of the 6th CTCF, closely correlated with sperm concentration.
      The methylation state of DMR0 and of the 3rd CTCF was never affected by the
      pathological status of sperm samples. This study demonstrates that epigenetic
      perturbations of the 6th CTCF site of the H19 DMR might be a relevant biomarker
      for quantitative defects of spermatogenesis in humans. Moreover, we defined a
      methylation threshold sustaining the classification of patients in two groups,
      unmethylated and methylated. Using this new classification of patients, the
      observed intrinsic imprinting defects of spermatozoa appear not to impair
      significantly the outcome of assisted reproductive technologies.

PMID- 19584899
TI  - Gene and pathway-based second-wave analysis of genome-wide association studies.
AB  - Despite the great success of genome-wide association studies (GWAS) in
      identification of the common genetic variants associated with complex diseases,
      the current GWAS have focused on single-SNP analysis. However, single-SNP
      analysis often identifies only a few of the most significant SNPs that account
      for a small proportion of the genetic variants and offers only a limited
      understanding of complex diseases. To overcome these limitations, we propose gene
      and pathway-based association analysis as a new paradigm for GWAS. As a proof of
      concept, we performed a comprehensive gene and pathway-based association analysis
      of 13 published GWAS. Our results showed that the proposed new paradigm for GWAS
      not only identified the genes that include significant SNPs found by single-SNP
      analysis, but also detected new genes in which each single SNP conferred a small
      disease risk; however, their joint actions were implicated in the development of
      diseases. The results also showed that the new paradigm for GWAS was able to
      identify biologically meaningful pathways associated with the diseases, which
      were confirmed by a gene-set-rich analysis using gene expression data.

PMID- 19584900
TI  - Association of FTO variants with BMI and fat mass in the self-contained
      population of Sorbs in Germany.
AB  - The association between common variants in the FTO gene with weight, adiposity
      and body mass index (BMI) has now been widely replicated. Although the causal
      variant has yet to be identified, it most likely maps within a 47 kb region of
      intron 1 of FTO. We performed a genome-wide association study in the Sorbian
      population and evaluated the relationships between FTO variants and BMI and fat
      mass in this isolate of Slavonic origin resident in Germany. In a sample of 948
      Sorbs, we could replicate the earlier reported associations of intron 1 SNPs with
      BMI (eg, P-value=0.003, beta=0.02 for rs8050136). However, using genome-wide
      association data, we also detected a second independent signal mapping to a
      region in intron 2/3 about 40-60 kb away from the originally reported SNPs (eg,
      for rs17818902 association with BMI P-value=0.0006, beta=-0.03 and with fat mass
      P-value=0.0018, beta=-0.079). Both signals remain independently associated in the
      conditioned analyses. In conclusion, we extend the evidence that FTO variants are
      associated with BMI by putatively identifying a second susceptibility allele
      independent of that described earlier. Although further statistical analysis of
      these findings is hampered by the finite size of the Sorbian isolate, these
      findings should encourage other groups to seek alternative susceptibility
      variants within FTO (and other established susceptibility loci) using the
      opportunities afforded by analyses in populations with divergent mutational
      and/or demographic histories.

PMID- 19584901
TI  - On the use of sibling recurrence risks to select environmental factors liable to
      interact with genetic risk factors.
AB  - Gene-environment interactions are likely to be involved in the susceptibility to
      multifactorial diseases but are difficult to detect. Available methods usually
      concentrate on some particular genetic and environmental factors. In this paper,
      we propose a new method to determine whether a given exposure is susceptible to
      interact with unknown genetic factors. Rather than focusing on a specific genetic
      factor, the degree of familial aggregation is used as a surrogate for genetic
      factors. A test comparing the recurrence risks in sibs according to the exposure
      of indexes is proposed and its power is studied for varying values of model
      parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable
      for common diseases with moderate familial aggregation, only when the role of
      exposure has been clearly outlined. Interestingly, accounting for a sibling
      correlation for the exposure increases the power of EURECA. An application on a
      sample ascertained through one index affected with type 2 diabetes is presented
      where gene-environment interactions involving obesity and physical inactivity are
      investigated. Association of obesity with type 2 diabetes is clearly evidenced
      and a potential interaction involving this factor is suggested in Hispanics
      (P=0.045), whereas a clear gene-environment interaction is evidenced involving
      physical inactivity only in non-Hispanic whites (P=0.028). The proposed method
      might be of particular interest before genetic studies to help determine the
      environmental risk factors that will need to be accounted for to increase the
      power to detect genetic risk factors and to select the most appropriate samples
      to genotype.

PMID- 19584902
TI  - A comprehensive approach to haplotype-specific analysis by penalized likelihood.
AB  - Haplotypes can hold key information to understand the role of candidate genes in
      disease etiology. However, standard haplotype analysis has yet been able to fully
      reveal the information retained by haplotypes. In most analysis, haplotype
      inference focuses on relative effects compared with an arbitrarily chosen
      baseline haplotype. It does not depict the effect structure unless an additional
      inference procedure is used in a secondary post hoc analysis, and such analysis
      tends to be lack of power. In this study, we propose a penalized regression
      approach to systematically evaluate the pattern and structure of the haplotype
      effects. By specifying an L1 penalty on the pairwise difference of the haplotype
      effects, we present a model-based haplotype analysis to detect and to
      characterize the haplotypic association signals. The proposed method avoids the
      need to choose a baseline haplotype; it simultaneously carries out the effect
      estimation and effect comparison of all haplotypes, and outputs the haplotype
      group structure based on their effect size. Finally, our penalty weights are
      theoretically designed to balance the likelihood and the penalty term in an
      appropriate manner. The proposed method can be used as a tool to comprehend
      candidate regions identified from a genome or chromosomal scan. Simulation
      studies reveal the better abilities of the proposed method to identify the
      haplotype effect structure compared with the traditional haplotype association
      methods, demonstrating the informativeness and powerfulness of the proposed
      method.

PMID- 19584903
TI  - The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the
      development of paragangliomas in a large multigenerational family.
AB  - Germline mutations in SDHD predispose to the development of head and neck
      paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on
      the sex of the parent who transmits the mutation: paragangliomas only arise upon
      paternal transmission. In this study, both the risk of paraganglioma and
      phaeochromocytoma formation, and the risk of developing associated symptoms were
      investigated in 243 family members with the SDHD.D92Y founder mutation. By using
      the Kaplan-Meier method, age-specific penetrance was calculated separately for
      paraganglioma formation as defined by magnetic resonance imaging (MRI) and for
      paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms
      alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI
      detection of occult paragangliomas was included, penetrance was estimated to be
      54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70
      years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in
      8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one
      patient (3%). Although the majority of carriers of a paternally inherited SDHD
      mutation will eventually develop head and neck paragangliomas, we find a lower
      penetrance than previous estimates from studies based on predominantly index
      cases. The family-based study described here emphasizes the importance of the
      identification and inclusion of clinically unaffected mutation carriers in all
      estimates of penetrance. This finding will allow a more accurate genetic
      counseling and warrants a 'wait and scan' policy for asymptomatic paragangliomas,
      combined with biochemical screening for catecholamine excess in SDHD-linked
      patients.

PMID- 19584904
TI  - Comprehensive SNP-chip for retinitis pigmentosa-Leber congenital amaurosis
      diagnosis: new mutations and detection of mutational founder effects.
AB  - Fast and efficient high-throughput techniques are essential for the molecular
      diagnosis of highly heterogeneous hereditary diseases, such as retinitis
      pigmentosa (RP). We had previously approached RP genetic testing by devising a
      chip based on co-segregation analysis for the autosomal recessive forms. In this
      study, we aimed to design a diagnostic tool for all the known genes (40 up to
      now) responsible for the autosomal dominant and recessive RP and Leber congenital
      amaurosis (LCA). This new chip analyzes 240 single nucleotide polymorphisms
      (SNPs) (6 per gene) on a high-throughput genotyping platform (SNPlex, Applied
      Biosystems), and genetic diagnosis is based on the co-segregation analysis of SNP
      haplotypes in independent families. In a single genotyping step, the number of RP
      candidates to be screened for mutations is considerably reduced, and in the most
      informative families, all the candidates are ruled out at once. In a panel of RP
      Spanish pedigrees, the disease chip became a crucial tool for selecting those
      suitable for genome-wide RP gene search, and saved the burdensome direct
      mutational screening of every known RP gene. In a large adRP family, the chip
      allowed ruling out of all but the causative gene, and identification of an
      unreported null mutation (E181X) in PRPF31. Finally, on the basis of the
      conservation of the SNP haplotype linked to this pathogenic variant, we propose
      that the E181X mutation spread through a cohort of geographically isolated
      families by a founder effect.

PMID- 19584905
TI  - Differential effects of iodoacetamide and iodoacetate on glycolysis and
      glutathione metabolism of cultured astrocytes.
AB  - Iodoacetamide (IAA) and iodoacetate (IA) have frequently been used to inhibit
      glycolysis, since these compounds are known for their ability to irreversibly
      inhibit the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
      However, the consequences of a treatment with such thiol reagents on the
      glutathione (GSH) metabolism of brain cells have not been explored. Exposure of
      astroglia-rich primary cultures to IAA or IA in concentrations of up to 1 mM
      deprived the cells of GSH, inhibited cellular GAPDH activity, lowered cellular
      lactate production and caused a delayed cell death that was detectable after 90
      min of incubation. However, the two thiol reagents differed substantially in
      their potential to deprive cellular GSH and to inhibit astrocytic glycolysis. IAA
      depleted the cellular GSH content more efficiently than IA as demonstrated by
      half-maximal effects for IAA and IA that were observed at concentrations of about
      10 and 100 muM, respectively. In contrast, IA was highly efficient in
      inactivating GAPDH and lactate production with half-maximal effects observed
      already at a concentration below 100 muM, whereas IAA had to be applied in 10
      times higher concentration to inhibit lactate production by 50%. These
      substantial differences of IAA and IA to affect GSH content and glycolysis of
      cultured astrocytes suggest that in order to inhibit astrocytic glycolysis
      without substantially compromising the cellular GSH metabolism, IA - and not IAA 
      should be used in low concentrations and/or for short incubation periods.

PMID- 19584907
TI  - Agrobacterium-mediated gene transfer to cereal crop plants: current protocols for
      barley, wheat, triticale, and maize.
AB  - The development of powerful "omics" technologies has enabled researchers to
      identify many genes of interest for which comprehensive functional analyses are
      highly desirable. However, the production of lines which ectopically express
      recombinant genes, or those in which endogenous genes are knocked down via stable
      transformation, remains a major bottleneck for the association between genetics
      and gene function in monocotyledonous crops. Methods of effective DNA transfer
      into regenerable cells of immature embryos from cereals by means of Agrobacterium
      tumefaciens have been modified in a stepwise manner. The effect of particular
      improvement measures has often not been significantly evident, whereas their
      combined implementation has resulted in meaningful advances. Here, we provide
      updated protocols for the Agrobacterium-mediated generation of stably transgenic
      barley, wheat, triticale and maize. Based upon these methods, several hundred
      independent transgenic lines have been delivered, with efficiencies of inoculated
      embryos leading to stably transgenic plants reaching 86% in barley, 10% in wheat,
      4% in triticale, and 24% in maize.

PMID- 19584908
TI  - Clinical Significance of Skin Toxicity due to EGFR-Targeted Therapies.
AB  - Many small molecules and monoclonal antibodies blocking the activity of Epidermal
      Growth factor receptor (EGFR) have been developed and have shown clinical
      activity in patients with non-small cell lung cancer (NSCLC), pancreatic cancer,
      and colorectal cancer (CRC), and are in clinical development for a range of other
      solid tumors. The toxicity profile of such agents is characterized by a typical
      pattern of cutaneous reactions. In this paper we reviewed the current available
      data regarding the clinical significance of skin reaction due to EGFR targeted
      agents. We show that skin toxicity can be considered as predictive marker of
      response to such drugs and that it is not disease specific; however its potential
      prognostic value is still to be proven.

PMID- 19584906
TI  - Build-ups in the supply chain of the brain: on the neuroenergetic cause of
      obesity and type 2 diabetes mellitus.
AB  - Obesity and type 2 diabetes have become the major health problems in many
      industrialized countries. A few theoretical frameworks have been set up to derive
      the possible determinative cause of obesity. One concept views that food
      availability determines food intake, i.e. that obesity is the result of an
      external energy "push" into the body. Another one views that the energy milieu
      within the human organism determines food intake, i.e. that obesity is due to an
      excessive "pull" from inside the organism. Here we present the unconventional
      concept that a healthy organism is maintained by a "competent brain-pull" which
      serves systemic homeostasis, and that the underlying cause of obesity is
      "incompetent brain-pull", i.e. that the brain is unable to properly demand
      glucose from the body. We describe the energy fluxes from the environment,
      through the body, towards the brain with a mathematical "supply chain" model and
      test whether its predictions fit medical and experimental data sets from our and
      other research groups. In this way, we show data-based support of our hypothesis,
      which states that under conditions of food abundance incompetent brain-pull will
      lead to build-ups in the supply chain culminating in obesity and type 2 diabetes.
      In the same way, we demonstrate support of the related hypothesis, which states
      that under conditions of food deprivation a competent brain-pull mechanism is
      indispensable for the continuance of the brain s high energy level. In
      conclusion, we took the viewpoint of integrative physiology and provided evidence
      for the necessity of brain-pull mechanisms for the benefit of health. Along these
      lines, our work supports recent molecular findings from the field of
      neuroenergetics and continues the work on the "Selfish Brain" theory dealing with
      the maintenance of the cerebral and peripheral energy homeostasis.

PMID- 19584909
TI  - Combining dissimilarities in a Hyper Reproducing Kernel Hilbert Space for complex
      human cancer prediction.
AB  - DNA microarrays provide rich profiles that are used in cancer prediction
      considering the gene expression levels across a collection of related samples.
      Support Vector Machines (SVM) have been applied to the classification of cancer
      samples with encouraging results. However, they rely on Euclidean distances that
      fail to reflect accurately the proximities among sample profiles. Then, non
      Euclidean dissimilarities provide additional information that should be
      considered to reduce the misclassification errors. In this paper, we incorporate
      in the nu-SVM algorithm a linear combination of non-Euclidean dissimilarities.
      The weights of the combination are learnt in a (Hyper Reproducing Kernel Hilbert
      Space) HRKHS using a Semidefinite Programming algorithm. This approach allows us
      to incorporate a smoothing term that penalizes the complexity of the family of
      distances and avoids overfitting. The experimental results suggest that the
      method proposed helps to reduce the misclassification errors in several human
      cancer problems.

PMID- 19584910
TI  - The track of brain activity during the observation of TV commercials with the
      high-resolution EEG technology.
AB  - We estimate cortical activity in normal subjects during the observation of TV
      commercials inserted within a movie by using high-resolution EEG techniques. The
      brain activity was evaluated in both time and frequency domains by solving the
      associate inverse problem of EEG with the use of realistic head models. In
      particular, we recover statistically significant information about cortical areas
      engaged by particular scenes inserted within the TV commercial proposed with
      respect to the brain activity estimated while watching a documentary. Results
      obtained in the population investigated suggest that the statistically
      significant brain activity during the observation of the TV commercial was mainly
      concentrated in frontoparietal cortical areas, roughly coincident with the
      Brodmann areas 8, 9, and 7, in the analyzed population.

PMID- 19584911
TI  - AQP1 is not only a water channel: it contributes to cell migration through
      Lin7/beta-catenin.
AB  - BACKGROUND: AQP1 belongs to aquaporins family, water-specific, membrane-channel
      proteins expressed in diverse tissues. Recent papers showed that during
      angiogenesis, AQP1 is expressed preferentially by microvessels, favoring
      angiogenesis via the increase of permeability In particular, in AQP1 null mice,
      endothelial cell migration is impaired without altering their proliferation or
      adhesion. Therefore, AQP1 has been proposed as a novel promoter of tumor
      angiogenesis. METHODS/FINDINGS: Using targeted silencing of AQP1 gene expression,
      an impairment in the organization of F-actin and a reduced migration capacity was
      demonstrated in human endothelial and melanoma cell lines. Interestingly, we
      showed, for the first time, that AQP1 co-immunoprecipitated with Lin-7. Lin7-GFP
      experiments confirmed co-immunoprecipitation. In addition, the knock down of AQP1
      decreased the level of expression of Lin-7 and beta-catenin and the inhibition of
      proteasome contrasted partially such a decrease. CONCLUSIONS/SIGNIFICANCE: All
      together, our findings show that AQP1 plays a role inside the cells through Lin
      7/beta-catenin interaction. Such a role of AQP1 is the same in human melanoma and
      endothelial cells, suggesting that AQP1 plays a global physiological role. A
      model is presented.

PMID- 19584912
TI  - The status of wildlife in protected areas compared to non-protected areas of
      Kenya.
AB  - We compile over 270 wildlife counts of Kenya's wildlife populations conducted
      over the last 30 years to compare trends in national parks and reserves with
      adjacent ecosystems and country-wide trends. The study shows the importance of
      discriminating human-induced changes from natural population oscillations related
      to rainfall and ecological factors. National park and reserve populations have
      declined sharply over the last 30 years, at a rate similar to non-protected areas
      and country-wide trends. The protected area losses reflect in part their poor
      coverage of seasonal ungulate migrations. The losses vary among parks. The
      largest parks, Tsavo East, Tsavo West and Meru, account for a disproportionate
      share of the losses due to habitat change and the difficulty of protecting large
      remote parks. The losses in Kenya's parks add to growing evidence for wildlife
      declines inside as well as outside African parks. The losses point to the need to
      quantify the performance of conservation policies and promote integrated
      landscape practices that combine parks with private and community-based measures.

PMID- 19584913
TI  - Immunophenotypic lymphocyte profiles in human african trypanosomiasis.
AB  - Human African trypanosomiasis (HAT) is a deadly vector-born disease caused by an
      extracellular parasite, the trypanosome. Little is known about the cellular
      immune responses elicited by this parasite in humans. We used multiparameter flow
      cytometry to characterize leukocyte immunophenotypes in the blood and
      cerebrospinal fluid (CSF) of 33 HAT patients and 27 healthy controls identified
      during a screening campaign in Angola and Gabon. We evaluated the subsets and
      activation markers of B and T lymphocytes. Patients had a higher percentage of
      CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls,
      but lacked activated CD4+ T lymphocytes (CD25+). Patients displayed no increase
      in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+), but memory
      CD8 T-cell levels (CD8+CD45RA2) were significantly lower in patients than in
      controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2). No relationship
      was found between these blood immunophenotypes and disease severity (stage 1 vs
      2). However, CD19+ B-cell levels in the CSF increased with disease severity. The
      patterns of T and B cell activation in HAT patients suggest that immunomodulatory
      mechanisms may operate during infection. Determinations of CD19+ B-cell levels in
      the CSF could improve disease staging.

PMID- 19584915
TI  - Discovery of a novel prolactin in non-mammalian vertebrates: evolutionary
      perspectives and its involvement in teleost retina development.
AB  - BACKGROUND: The three pituitary hormones, viz. prolactin (PRL), growth hormone
      (GH) and somatolactin (SL), together with the mammalian placental lactogen (PL),
      constitute a gene family of hormones with similar gene structure and encoded
      protein sequences. These hormones are believed to have evolved from a common
      ancestral gene through several rounds of gene duplication and subsequent
      divergence. PRINCIPAL FINDINGS: In this study, we have identified a new PRL-like
      gene in non-mammalian vertebrates through bioinformatics and molecular cloning
      means. Phylogenetic analyses showed that this novel protein is homologous to the
      previously identified PRL. A receptor transactivation assay further showed that
      this novel protein could bind to PRL receptor to trigger the downstream post
      receptor event, indicating that it is biologically active. In view of its close
      phylogenetic relationship with PRL and also its ability to activate PRL receptor,
      we name it as PRL2 and the previously identified PRL as PRL1. All the newly
      discovered PRL2 sequences possess three conserved disulfide linkages with the
      exception of the shark PRL2 which has only two. In sharp contrast to the
      classical PRL1 which is predominantly expressed in the pituitary, PRL2 was found
      to be mainly expressed in the eye and brain of the zebrafish but not in the
      pituitary. A largely reduced inner nuclear layer of the retina was observed after
      morpholino knockdown of zebrafish PRL2, indicating its role on retina development
      in teleost. SIGNIFICANCE: The discovery of this novel PRL has revitalized our
      understanding on the evolution of the GH/PRL/SL/PL gene family. Its unique
      expression and functions in the zebrafish eye also provide a new avenue of
      research on the neuroendocrine control of retina development in vertebrates.

PMID- 19584914
TI  - LPS-induced genes in intestinal tissue of the sea cucumber Holothuria glaberrima.
AB  - Metazoan immunity is mainly associated with specialized cells that are directly
      involved with the immune response. Nevertheless, both in vertebrates and
      invertebrates other organs might respond to immune activation and participate
      either directly or indirectly in the ongoing immune process. However, most of
      what is known about invertebrate immunity has been restricted to immune effector
      cells and little information is available on the immune responses of other
      tissues or organs. We now focus on the immune reactions of the intestinal tissue
      of an echinoderm. Our study employs a non-conventional model, the echinoderm
      Holothuria glaberrima, to identify intestinal molecules expressed after an immune
      challenge presented by an intra-coelomic injection of lipopolysaccharides (LPS).
      The expression profiles of intestinal genes expressed differentially between LPS
      injected animals and control sea water-injected animals were determined using a
      custom-made Agilent microarray with 7209 sea cucumber intestinal ESTs. Fifty (50)
      unique sequences were found to be differentially expressed in the intestine of
      LPS-treated sea cucumbers. Seven (7) of these sequences represented homologues of
      known proteins, while the remaining (43) had no significant similarity with any
      protein, EST or RNA database. The known sequences corresponded to cytoskeletal
      proteins (Actin and alpha-actinin), metabolic enzymes (GAPDH, Ahcy and Gnmt),
      metal ion transport/metabolism (major yolk protein) and defense/recognition
      (fibrinogen-like protein). The expression pattern of 11 genes was validated using
      semi-quantitative RT-PCR. Nine of these corroborated the microarray results and
      the remaining two showed a similar trend but without statistical significance.
      Our results show some of the molecular events by which the holothurian intestine
      responds to an immune challenge and provide important information to the study of
      the evolution of the immune response.

PMID- 19584916
TI  - Cytotoxic effect of recombinant Mycobacterium tuberculosis CFP-10/ESAT-6 protein
      on the crucial pathways of WI-38 cells.
AB  - To unravel the cytotoxic effect of the recombinant CFP-10/ESAT-6 protein (rCFES)
      on WI-38 cells, an integrative analysis approach, combining time-course
      microarray data and annotated pathway databases, was proposed with the emphasis
      on identifying the potentially crucial pathways. The potentially crucial pathways
      were selected based on a composite criterion characterizing the average
      significance and topological properties of important genes. The analysis results
      suggested that the regulatory effect of rCFES was at least involved in cell
      proliferation, cell motility, cell survival, and metabolisms of WI-38 cells. The
      survivability of WI-38 cells, in particular, was significantly decreased to 62%
      with 12.5 microM rCFES. Furthermore, the focal adhesion pathway was identified as
      the potentially most-crucial pathway and 58 of 65 important genes in this pathway
      were downregulated by rCFES treatment. Using qRT-PCR, we have confirmed the
      changes in the expression levels of LAMA4, PIK3R3, BIRC3, and NFKBIA, suggesting
      that these proteins may play an essential role in the cytotoxic process in the
      rCFES-treated WI-38 cells.

PMID- 19584917
TI  - Inflammation but not endothelial dysfunction is associated with the severity of
      coronary artery disease in dyslipidemic subjects.
AB  - INTRODUCTION: Endothelial dysfunction and inflammation play a key role in the
      development of atherosclerosis. The present study evaluated endothelial function,
      inflammatory parameters, and carotid intima-media thickness (IMT) in dyslipidemic
      patients with or without coronary artery disease (CAD). METHODS: Metabolic
      profile and inflammatory parameters were determined in dyslipidemic patients with
      (+CAD, n = 33) and without (-CAD, n = 69) symptomatic CAD. Endothelial function
      was evaluated by flow mediated dilatation (FMD) and plasma concentration of
      nitrites and nitrates. Carotid IMT was measured by ultrasound. RESULTS: No
      significant differences were observed in anthropometric hemodynamic or metabolic
      parameters between the groups. After adjusting by age and medication usage, some
      inflammatory markers were significantly higher in +CAD; however no significant
      differences in FMD or plasma levels of nitrites were observed. CONCLUSIONS: In
      subjects with dyslipidemia, the presence of CAD is associated with an elevation
      of certain inflammatory markers and carotid IMT but not with further endothelial
      dysfunction.

PMID- 19584918
TI  - Developing prognostic systems of cancer patients by ensemble clustering.
AB  - Accurate prediction of survival rates of cancer patients is often key to stratify
      patients for prognosis and treatment. Survival prediction is often accomplished
      by the TNM system that involves only three factors: tumor extent, lymph node
      involvement, and metastasis. This prediction from the TNM has been limited,
      because other potential prognostic factors are not used in the system. Based on
      availability of large cancer datasets, it is possible to establish powerful
      prediction systems by using machine learning procedures and statistical methods.
      In this paper, we present an ensemble clustering-based approach to develop
      prognostic systems of cancer patients. Our method starts with grouping
      combinations that are formed using levels of factors recorded in the data. The
      dissimilarity measure between combinations is obtained through a sequence of data
      partitions produced by multiple use of PAM algorithm. This dissimilarity measure
      is then used with a hierarchical clustering method in order to find clusters of
      combinations. Prediction of survival is made simply by using the survival
      function derived from each cluster. Our approach admits multiple factors and
      provides a practical and useful tool in outcome prediction of cancer patients. A
      demonstration of use of the proposed method is given for lung cancer patients.

PMID- 19584919
TI  - Self reported incidence and morbidity of acute respiratory illness among deployed
      U.S. military in Iraq and Afghanistan.
AB  - BACKGROUND: Historically, respiratory infections have had a significant impact on
      U.S. military missions. Deployed troops are particularly at high risk due to
      close living conditions, stressful work environments and increased exposure to
      pathogens. To date, there are limited data available on acute respiratory illness
      (ARI) among troops deployed in support of ongoing military operations,
      specifically Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF).
      METHODS: Using self-report data from two sources collected from troops deployed
      to Iraq, Afghanistan and the surrounding region, we analyzed incidence and risk
      factors for ARI. Military personnel on mid-deployment Rest & Recuperation (R&R)
      or during redeployment were eligible to participate in the voluntary self-report
      survey. RESULTS: Overall, 39.5% reported having at least one ARI. Of these, 18.5%
      sought medical care and 33.8% reported having decreased job performance. The rate
      of self-reported ARI was 15 episodes per 100 person-months among those taking the
      voluntary survey, and 24.7 episodes per 100 person-months among those taking the
      clinic health questionnaire. Negative binomial regression analysis found female
      sex, Navy branch of service and lack of flush toilets to be independently
      associated with increased rates of ARI. Deployment to OIF, increasing age and
      higher rank were also positively associated with ARI risk. CONCLUSIONS: The
      overall percentage of deployed military personnel reporting at least one acute
      respiratory illness decreased since earlier parts of OIF/OEF. However, the
      reported effect on job performance increased tremendously. The most important
      factors associated with increased respiratory infection are female sex, Navy
      branch of service, lack of improved latrine facilities, deployment to OIF,
      increasing age and higher rank.

PMID- 19584921
TI  - L-dopa medication in Parkinson's disease restores activity in the motor cortico
      striatal loop but does not modify the cognitive network.
AB  - BACKGROUND: The goal of this study was to evaluate the effects of L-Dopa
      medication in Parkinson's disease (PD) on brain activation during the performance
      of a set-shifting task. Using fMRI, we have previously studied the patterns of
      activity observed in patients with PD after overnight removal of dopaminergic
      medication compared with control participants during the performance of different
      stages of the Wisconsin Card Sorting Task (WCST). The results revealed decreased
      cortical activity in the PD group compared to controls in the conditions that
      significantly required striatum, while increased cortical activity was observed
      when striatum was not involved. However, the effect of dopaminergic medication in
      PD patients on those patterns of activity has not yet been studied.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, eleven PD patients at early stage of the
      disease taking L-Dopa medication were recruited and underwent two fMRI sessions
      while performing the WCST: one session while taking their normal dose of
      medication and the other following overnight dopaminergic medication withdrawal.
      We found that L-dopa medication helped restoring a normal pattern of activity
      when matching and not planning was required, by increasing cortical activity in
      the premotor cortex. This effect was even stronger in the motor loop, i.e. when
      the putamen was required for controls, when matching following negative feedback.
      However, the medication did not change the pattern of activity in conditions
      relying primarily on a cognitive loop, i.e. when the caudate nucleus was
      required. CONCLUSIONS/SIGNIFICANCE: These studies provide explanation at the
      neural level regarding the relatively poor effects of L-Dopa on the cognitive
      deficits observed in PD.

PMID- 19584920
TI  - PINP: a new method of tagging neuronal populations for identification during in
      vivo electrophysiological recording.
AB  - Neural circuits are exquisitely organized, consisting of many different neuronal
      subpopulations. However, it is difficult to assess the functional roles of these
      subpopulations using conventional extracellular recording techniques because
      these techniques do not easily distinguish spikes from different neuronal
      populations. To overcome this limitation, we have developed PINP
      (Photostimulation-assisted Identification of Neuronal Populations), a method of
      tagging neuronal populations for identification during in vivo
      electrophysiological recording. The method is based on expressing the light
      activated channel channelrhodopsin-2 (ChR2) to restricted neuronal
      subpopulations. ChR2-tagged neurons can be detected electrophysiologically in
      vivo since illumination of these neurons with a brief flash of blue light
      triggers a short latency reliable action potential. We demonstrate the
      feasibility of this technique by expressing ChR2 in distinct populations of
      cortical neurons using two different strategies. First, we labeled a
      subpopulation of cortical neurons-mainly fast-spiking interneurons-by using adeno
      associated virus (AAV) to deliver ChR2 in a transgenic mouse line in which the
      expression of Cre recombinase was driven by the parvalbumin promoter. Second, we
      labeled subpopulations of excitatory neurons in the rat auditory cortex with ChR2
      based on projection target by using herpes simplex virus 1 (HSV1), which is
      efficiently taken up by axons and transported retrogradely; we find that this
      latter population responds to acoustic stimulation differently from unlabeled
      neurons. Tagging neurons is a novel application of ChR2, used in this case to
      monitor activity instead of manipulating it. PINP can be readily extended to
      other populations of genetically identifiable neurons, and will provide a useful
      method for probing the functional role of different neuronal populations in vivo.

PMID- 19584922
TI  - Characterization of voltage-gated potassium channels in human neural progenitor
      cells.
AB  - BACKGROUND: Voltage-gated potassium (K(v)) channels are among the earliest ion
      channels to appear during brain development, suggesting a functional requirement
      for progenitor cell proliferation and/or differentiation. We tested this
      hypothesis, using human neural progenitor cells (hNPCs) as a model system.
      METHODOLOGY/PRINCIPAL FINDINGS: In proliferating hNPCs a broad spectrum of K(v)
      channel subtypes was identified using quantitative real-time PCR with a
      predominant expression of the A-type channel K(v)4.2. In whole-cell patch-clamp
      recordings K(v) currents were separated into a large transient component
      characteristic for fast-inactivating A-type potassium channels (I(A)) and a
      small, sustained component produced by delayed-rectifying channels (I(K)). During
      differentiation the expression of I(A) as well as A-type channel transcripts
      dramatically decreased, while I(K) producing delayed-rectifiers were upregulated.
      Both K(v) currents were differentially inhibited by selective neurotoxins like
      phrixotoxin-1 and alpha-dendrotoxin as well as by antagonists like 4
      aminopyridine, ammoniumchloride, tetraethylammonium chloride and quinidine. In
      viability and proliferation assays chronic inhibition of the A-type currents
      severely disturbed the cell cycle and precluded proper hNPC proliferation, while
      the blockade of delayed-rectifiers by alpha-dendrotoxin increased proliferation.
      CONCLUSIONS/SIGNIFICANCE: These findings suggest that A-type potassium currents
      are essential for proper proliferation of immature multipotent hNPCs.

PMID- 19584923
TI  - Pyrin Modulates the Intracellular Distribution of PSTPIP1.
AB  - PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type
      phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome
      (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory
      disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial
      Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease
      associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are
      thought to share a common pathoetiology. The studies outlined here describe
      several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which
      has homology to membrane-deforming BAR proteins, forms homodimers and generates
      membrane-associated filaments in native and transfected cells. An extended FCH
      (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self
      aggregation. We further show that the PSTPIP1 filament network is dependent upon
      an intact tubulin cytoskeleton and that the distribution of this network can be
      modulated by pyrin, indicating that this is a dynamic structure. Finally, we
      demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC,
      another pyrin binding protein. ASC specks are associated with inflammasome
      activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin
      to ASC specks with particularly high efficiency, suggesting a unique mechanism
      underlying the robust inflammatory phenotype of PAPA syndrome.

PMID- 19584924
TI  - Amplification and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at
      8q24.22-q24.23 in medulloblastoma.
AB  - BACKGROUND: Medulloblastoma is the most common malignant brain tumour of
      childhood. The identification of critical genes involved in its pathogenesis will
      be central to advances in our understanding of its molecular basis, and the
      development of improved therapeutic approaches. METHODOLOGY/PRINCIPAL FINDINGS:
      We performed a SNP-array based genome-wide copy number analysis in
      medulloblastoma cell lines, to identify regions of genomic amplification and
      homozygous deletion, which may harbour critical disease genes. A series of novel
      and established medulloblastoma defects were detected (MYC amplification (n = 4),
      17q21.31 high-level gain (n = 1); 9p21.1-p21.3 (n = 1) and 6q23.1 (n = 1)
      homozygous deletion). Most notably, a novel recurrent region of genomic
      amplification at 8q24.22-q24.23 was identified (n = 2), and selected for further
      investigation. Additional analysis by interphase fluorescence in situ
      hybridisation (iFISH), PCR-based mapping and SNP-array revealed this novel
      amplification at 8q24.22-q24.23 is independent of MYC amplification at 8q24.21,
      and is unique to medulloblastoma in over 800 cancer cell lines assessed from
      different tumour types, suggesting it contains key genes specifically involved in
      medulloblastoma development. Detailed mapping identified a 3Mb common minimal
      region of amplification harbouring 3 coding genes (ZFAT1, LOC286094, KHDRBS3) and
      two genes encoding micro-RNAs (hsa-miR-30b, hsa-miR-30d). Of these, only
      expression of hsa-miR-30b, hsa-miR-30d and KHDRBS3 correlated with copy number
      status, and all three of these transcripts also displayed evidence of elevated
      expression in sub-sets of primary medulloblastomas, measured relative to the
      normal cerebellum. CONCLUSIONS/SIGNIFICANCE: These data implicate hsa-miR-30b,
      hsa-miR-30d and KHDRBS3 as putative oncogenic target(s) of a novel recurrent
      medulloblastoma amplicon at 8q24.22-q24.23. Our findings suggest critical roles
      for these genes in medulloblastoma development, and further support the
      contribution of micro-RNA species to medulloblastoma pathogenesis.

PMID- 19584925
TI  - Evidence for the concerted evolution between short linear protein motifs and
      their flanking regions.
AB  - BACKGROUND: Linear motifs are short modules of protein sequences that play a
      crucial role in mediating and regulating many protein-protein interactions. The
      function of linear motifs strongly depends on the context, e.g. functional
      instances mainly occur inside flexible regions that are accessible for
      interaction. Sometimes linear motifs appear as isolated islands of conservation
      in multiple sequence alignments. However, they also occur in larger blocks of
      sequence conservation, suggesting an active role for the neighbouring amino
      acids. RESULTS: The evolution of regions flanking 116 functional linear motif
      instances was studied. The conservation of the amino acid sequence and
      order/disorder tendency of those regions was related to presence/absence of the
      instance. For the majority of the analysed instances, the pairs of sequences
      conserving the linear motif were also observed to maintain a similar local
      structural tendency and/or to have higher local sequence conservation when
      compared to pairs of sequences where one is missing the linear motif.
      Furthermore, those instances have a higher chance to co-evolve with the
      neighbouring residues in comparison to the distant ones. Those findings are
      supported by examples where the regulation of the linear motif-mediated
      interaction has been shown to depend on the modifications (e.g. phosphorylation)
      at neighbouring positions or is thought to benefit from the binding versatility
      of disordered regions. CONCLUSION: The results suggest that flanking regions are
      relevant for linear motif-mediated interactions, both at the structural and
      sequence level. More interestingly, they indicate that the prediction of linear
      motif instances can be enriched with contextual information by performing a
      sequence analysis similar to the one presented here. This can facilitate the
      understanding of the role of these predicted instances in determining the protein
      function inside the broader context of the cellular network where they arise.

PMID- 19584926
TI  - Impact of exercise in community-dwelling older adults.
AB  - BACKGROUND: Concern has been expressed that preventive measures in older people
      might increase frailty by increasing survival without improving health. We
      investigated the impact of exercise on the probabilities of health improvement,
      deterioration and death in community-dwelling older people. METHODS AND PRINCIPAL
      FINDINGS: In the Canadian Study of Health and Aging, health status was measured
      by a frailty index based on the number of health deficits. Exercise was
      classified as either high or low/no exercise, using a validated, self
      administered questionnaire. Health status and survival were re-assessed at 5
      years. Of 6297 eligible participants, 5555 had complete data. Across all grades
      of frailty, death rates for both men and women aged over 75 who exercised were
      similar to their peers aged 65 to 75 who did not exercise. In addition, while all
      those who exercised had a greater chance of improving their health status, the
      greatest benefits were in those who were more frail (e.g. improvement or
      stability was observed in 34% of high exercisers versus 26% of low/no exercisers
      for those with 2 deficits compared with 40% of high exercisers versus 22% of
      low/no exercisers for those with 9 deficits at baseline). CONCLUSIONS: In
      community-dwelling older people, exercise attenuated the impact of age on
      mortality across all grades of frailty. Exercise conferred its greatest benefits
      to improvements in health status in those who were more frail at baseline. The
      net effect of exercise should therefore be to improve health status at the
      population level.

PMID- 19584927
TI  - Local calcium elevation and cell elongation initiate guided motility in
      electrically stimulated osteoblast-like cells.
AB  - BACKGROUND: Investigation of the mechanisms of guided cell migration can
      contribute to our understanding of many crucial biological processes, such as
      development and regeneration. Endogenous and exogenous direct current electric
      fields (dcEF) are known to induce directional cell migration, however the initial
      cellular responses to electrical stimulation are poorly understood. Ion fluxes,
      besides regulating intracellular homeostasis, have been implicated in many
      biological events, including regeneration. Therefore understanding intracellular
      ion kinetics during EF-directed cell migration can provide useful information for
      development and regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the
      initial events during migration of two osteogenic cell types, rat calvarial and
      human SaOS-2 cells, exposed to strong (10-15 V/cm) and weak (< or = 5 V/cm)
      dcEFs. Cell elongation and perpendicular orientation to the EF vector occurred in
      a time- and voltage-dependent manner. Calvarial osteoblasts migrated to the
      cathode as they formed new filopodia or lamellipodia and reorganized their
      cytoskeleton on the cathodal side. SaOS-2 cells showed similar responses except
      towards the anode. Strong dcEFs triggered a rapid increase in intracellular
      calcium levels, whereas a steady state level of intracellular calcium was
      observed in weaker fields. Interestingly, we found that dcEF-induced
      intracellular calcium elevation was initiated with a local rise on opposite sides
      in calvarial and SaOS-2 cells, which may explain their preferred directionality.
      In calcium-free conditions, dcEFs induced neither intracellular calcium elevation
      nor directed migration, indicating an important role for calcium ions. Blocking
      studies using cadmium chloride revealed that voltage-gated calcium channels
      (VGCCs) are involved in dcEF-induced intracellular calcium elevation.
      CONCLUSION/SIGNIFICANCE: Taken together, these data form a time scale of the
      morphological and physiological rearrangements underlying EF-guided migration of
      osteoblast-like cell types and reveal a requirement for calcium in these
      reactions. We show for the first time here that dcEFs trigger different patterns
      of intracellular calcium elevation and positional shifting in osteogenic cell
      types that migrate in opposite directions.

PMID- 19584928
TI  - Signatures of depression in non-stationary biometric time series.
AB  - This paper is based on a discussion that was held during a special session on
      models of mental disorders, at the NeuroMath meeting in Stockholm, Sweden, in
      September 2008. At this occasion, scientists from different countries and
      different fields of research presented their research and discussed open
      questions with regard to analyses and models of mental disorders, in particular
      depression. The content of this paper emerged from these discussions and in the
      presentation we briefly link biomarkers (hormones), bio-signals (EEG) and biomaps
      (brain-maps via EEG) to depression and its treatments, via linear statistical
      models as well as nonlinear dynamic models. Some examples involving EEG-data are
      presented.

PMID- 19584929
TI  - New Mid-Cretaceous (latest Albian) dinosaurs fromWinton, Queensland, Australia.
AB  - BACKGROUND: Australia's dinosaurian fossil record is exceptionally poor compared
      to that of other similar-sized continents. Most taxa are known from fragmentary
      isolated remains with uncertain taxonomic and phylogenetic placement. A better
      understanding of the Australian dinosaurian record is crucial to understanding
      the global palaeobiogeography of dinosaurian groups, including groups previously
      considered to have had Gondwanan origins, such as the titanosaurs and
      carcharodontosaurids. METHODOLOGY/PRINCIPAL FINDINGS: We describe three new
      dinosaurs from the late Early Cretaceous (latest Albian) Winton Formation of
      eastern Australia, including; Wintonotitan wattsi gen. et sp. nov., a basal
      titanosauriform; Diamantinasaurus matildae gen. et sp. nov., a derived
      lithostrotian titanosaur; and Australovenator wintonensis gen. et sp. nov., an
      allosauroid. We compare an isolated astragalus from the Early Cretaceous of
      southern Australia; formerly identified as Allosaurus sp., and conclude that it
      most-likely represents Australovenator sp. CONCLUSION/SIGNIFICANCE: The
      occurrence of Australovenator from the Aptian to latest Albian confirms the
      presence in Australia of allosauroids basal to the Carcharodontosauridae. These
      new taxa, along with the fragmentary remains of other taxa, indicate a diverse
      Early Cretaceous sauropod and theropod fauna in Australia, including
      plesiomorphic forms (e.g. Wintonotitan and Australovenator) and more derived
      forms (e.g. Diamantinasaurus).

PMID- 19584930
TI  - Cytoprotective Nrf2 pathway is induced in chronically txnrd 1-deficient
      hepatocytes.
AB  - BACKGROUND: Metabolically active cells require robust mechanisms to combat
      oxidative stress. The cytoplasmic thioredoxin reductase/thioredoxin (Txnrd1/Txn1)
      system maintains reduced protein dithiols and provides electrons to some cellular
      reductases, including peroxiredoxins. PRINCIPAL FINDINGS: Here we generated mice
      in which the txnrd1 gene, encoding Txnrd1, was specifically disrupted in all
      parenchymal hepatocytes. Txnrd1-deficient livers exhibited a transcriptome
      response in which 56 mRNAs were induced and 12 were repressed. Based on the
      global hybridization profile, this represented only 0.3% of the liver
      transcriptome. Since most liver mRNAs were unaffected, compensatory responses
      were evidently effective. Nuclear pre-mRNA levels indicated the response was
      transcriptional. Twenty-one of the induced genes contained known antioxidant
      response elements (AREs), which are binding sites for the oxidative and chemical
      stress-induced transcription factor Nrf2. Txnrd1-deficient livers showed
      increased accumulation of nuclear Nrf2 protein and chromatin immunoprecipitation
      on the endogenous nqo1 and aox1 promoters in fibroblasts indicated that Txnrd1
      ablation triggered in vivo assembly of Nrf2 on each. CONCLUSIONS: Chronic
      deletion of Txnrd1 results in induction of the Nrf2 pathway, which contributes to
      an effective compensatory response.

PMID- 19584931
TI  - Drosophila RISC component VIG and its homolog Vig2 impact heterochromatin
      formation.
AB  - Heterochromatin formation plays an important role in gene regulation and the
      maintenance of genome integrity. Here we present results from a study of the D.
      melanogaster gene vig, encoding an RNAi complex component and its homolog vig2
      (CG11844) that support their involvement in heterochromatin formation and/or
      maintenance. Protein null mutations vig(EP812) and vig2(PL470) act as modifiers
      of Position Effect Variegation (PEV). VIG and Vig2 are present in polytene
      chromosomes and partially overlap with HP1. Quantitative immunoblots show
      depletion of HP1 and HP2 (large isoform) in isolated nuclei from the vig(EP812)
      mutant. The vig2(PL470) mutant strain demonstrates a decreased level of H3K9me2.
      Pull-down experiments using antibodies specific to HP1 recovered both VIG and
      Vig2. The association between HP1 and both VIG and Vig2 proteins depends on an
      RNA component. The above data and the developmental profiles of the two genes
      suggest that Vig2 may be involved in heterochromatin targeting and establishment
      early in development, while VIG may have a role in stabilizing HP1/HP2 chromatin
      binding during later stages.

PMID- 19584932
TI  - Gene-based multiclass cancer diagnosis with class-selective rejections.
AB  - Supervised learning of microarray data is receiving much attention in recent
      years. Multiclass cancer diagnosis, based on selected gene profiles, are used as
      adjunct of clinical diagnosis. However, supervised diagnosis may hinder patient
      care, add expense or confound a result. To avoid this misleading, a multiclass
      cancer diagnosis with class-selective rejection is proposed. It rejects some
      patients from one, some, or all classes in order to ensure a higher reliability
      while reducing time and expense costs. Moreover, this classifier takes into
      account asymmetric penalties dependent on each class and on each wrong or
      partially correct decision. It is based on nu-1-SVM coupled with its
      regularization path and minimizes a general loss function defined in the class
      selective rejection scheme. The state of art multiclass algorithms can be
      considered as a particular case of the proposed algorithm where the number of
      decisions is given by the classes and the loss function is defined by the
      Bayesian risk. Two experiments are carried out in the Bayesian and the class
      selective rejection frameworks. Five genes selected datasets are used to assess
      the performance of the proposed method. Results are discussed and accuracies are
      compared with those computed by the Naive Bayes, Nearest Neighbor, Linear
      Perceptron, Multilayer Perceptron, and Support Vector Machines classifiers.

PMID- 19584933
TI  - Analysis of Gene Expression Profiles in Leaf Tissues of Cultivated Peanuts and
      Development of EST-SSR Markers and Gene Discovery.
AB  - Peanut is vulnerable to a range of foliar diseases such as spotted wilt caused by
      Tomato spotted wilt virus (TSWV), early (Cercospora arachidicola) and late
      (Cercosporidium personatum) leaf spots, southern stem rot (Sclerotium rolfsii),
      and sclerotinia blight (Sclerotinia minor). In this study, we report the
      generation of 17,376 peanut expressed sequence tags (ESTs) from leaf tissues of a
      peanut cultivar (Tifrunner, resistant to TSWV and leaf spots) and a breeding line
      (GT-C20, susceptible to TSWV and leaf spots). After trimming vector and
      discarding low quality sequences, a total of 14,432 high-quality ESTs were
      selected for further analysis and deposition to GenBank. Sequence clustering
      resulted in 6,888 unique ESTs composed of 1,703 tentative consensus (TCs)
      sequences and 5185 singletons. A large number of ESTs (5717) representing genes
      of unknown functions were also identified. Among the unique sequences, there were
      856 EST-SSRs identified. A total of 290 new EST-based SSR markers were developed
      and examined for amplification and polymorphism in cultivated peanut and wild
      species. Resequencing information of selected amplified alleles revealed that
      allelic diversity could be attributed mainly to differences in repeat type and
      length in the SSR regions. In addition, a few additional INDEL mutations and
      substitutions were observed in the regions flanking the microsatellite regions.
      In addition, some defense-related transcripts were also identified, such as
      putative oxalate oxidase (EU024476) and NBS-LRR domains. EST data in this study
      have provided a new source of information for gene discovery and development of
      SSR markers in cultivated peanut. A total of 16931 ESTs have been deposited to
      the NCBI GenBank database with accession numbers ES751523 to ES768453.

PMID- 19584934
TI  - Right porto-ovarian H-shunt for the surgical treatment of symptomatic portal
      biliopathy: a case report and literature review.
AB  - Portal hypertension, especially when it is caused by extrahepatic portal vein
      thrombosis, is commonly followed by the development of an abnormal periportal and
      pericholedochal variceal network, which form a portal cavernoma. This may exert
      extrinsic pressure on the adjacent biliary ducts and gallblader, causing
      morphologic abnormalities, termed portal biliopathy, which is usually leading to
      asymptomatic cholestasis, while less frequently it can be associated with
      obstructive jaundice, gallstone formation, and cholangitis. Endoscopic stone
      extraction can effectively treat portal biliopathy when cholangitis is associated
      with common bile duct stones. Portosystemic shunts are indicated in cases of
      disease recurrence as they can achieve regression of portal cavernoma and usually
      relieve symptomatic portal biliopathy. This case describes an alternative partial
      portosystemic shunt that utilizes the right ovarian vein as an autologous conduit
      for the surgical treatment of symptomatic portal biliopathy.

PMID- 19584935
TI  - Migratory status is not related to the susceptibility to HPAIV H5N1 in an
      insectivorous passerine species.
AB  - Migratory birds have evolved elaborate physiological adaptations to travelling,
      the implications for their susceptibility to avian influenza are however unknown.
      Three groups of stonechats (Saxicola torquata) from (I) strongly migrating, (II)
      weakly migrating and (III) non-migrating populations were experimentally infected
      with HPAIV H5N1. The different bird groups of this insectivorous passerine
      species were infected in autumn, when the migrating populations clearly exhibit
      migratory restlessness. Following infection, all animals succumbed to the disease
      from 3 through 7 days post inoculation. Viral shedding, antigen distribution in
      tissues, and survival time did not differ between the three populations. However,
      notably, endothelial tropism of the HPAIV infection was exclusively seen in the
      group of resident birds. In conclusion, our data document for the first time the
      high susceptibility of an insectivorous passerine species to H5N1 infection, and
      the epidemiological role of these passerine birds is probably limited due to
      their high sensitivity to HPAIV H5N1 infection. Despite pronounced inherited
      differences in migratory status, the groups were generally indistinguishable in
      their susceptibility, survival time, clinical symptoms and viral shedding.
      Nevertheless, the migratory status partly influenced pathogenesis in the way of
      viral tropism.

PMID- 19584936
TI  - Prediction and interaction in complex disease genetics: experience in type 1
      diabetes.

PMID- 19584937
TI  - Identification of novel reference genes using multiplatform expression data and
      their validation for quantitative gene expression analysis.
AB  - Normalization of mRNA levels using endogenous reference genes (ERGs) is critical
      for an accurate comparison of gene expression between different samples. Despite
      the popularity of traditional ERGs (tERGs) such as GAPDH and ACTB, their
      expression variability in different tissues or disease status has been reported.
      Here, we first selected candidate housekeeping genes (HKGs) using human gene
      expression data from different platforms including EST, SAGE, and microarray, and
      13 novel ERGs (nERGs) (ARL8B, CTBP1, CUL1, DIMT1L, FBXW2, GPBP1, LUC7L2, OAZ1,
      PAPOLA, SPG21, TRIM27, UBQLN1, ZNF207) were further identified from these HKGs.
      The mean coefficient variation (CV) values of nERGs were significantly lower than
      those of tERGs and the expression level of most nERGs was relatively lower than
      high expressing tERGs in all dataset. The higher expression stability and lower
      expression levels of most nERGs were validated in 108 human samples including
      formalin-fixed paraffin-embedded (FFPE) tissues, frozen tissues and cell lines,
      through quantitative real-time RT-PCR (qRT-PCR). Furthermore, the optimal number
      of nERGs required for accurate normalization was as few as two, while four genes
      were required when using tERGs in FFPE tissues. Most nERGs identified in this
      study should be better reference genes than tERGs, based on their higher
      expression stability and fewer numbers needed for normalization when multiple
      ERGs are required.

PMID- 19584938
TI  - Measurement of brain function of car driver using functional near-infrared
      spectroscopy (fNIRS).
AB  - The aim of this study is to propose a method for analyzing measured signal
      obtained from functional Near-Infrared Spectroscopy (fNIRS), which is applicable
      for neuroimaging studies for car drivers. We developed a signal processing method
      by multiresolution analysis (MRA) based on discrete wavelet transform.
      Statistical group analysis using Z-score is conducted after the extraction of
      task-related signal using MRA. Brain activities of subjects with different level
      of mental calculation are measured by fNIRS and fMRI. Results of mental
      calculation with nine subjects by using fNIRS and fMRI showed that the proposed
      methods were effective for the evaluation of brain activities due to the task.
      Finally, the proposed method is applied for evaluating brain function of car
      driver with and without adaptive cruise control (ACC) system for demonstrating
      the effectiveness of the proposed method. The results showed that frontal lobe
      was less active when the subject drove with ACC.

PMID- 19584940
TI  - On the relation between bursts and dynamic synapse properties: a modulation-based
      ansatz.
AB  - When entering a synapse, presynaptic pulse trains are filtered according to the
      recent pulse history at the synapse and also with respect to their own pulse time
      course. Various behavioral models have tried to reproduce these complex filtering
      properties. In particular, the quantal model of neurotransmitter release has been
      shown to be highly selective for particular presynaptic pulse patterns. However,
      since the original, pulse-iterative quantal model does not lend itself to
      mathematical analysis, investigations have only been carried out via simulations.
      In contrast, we derive a comprehensive explicit expression for the quantal model.
      We show the correlation between the parameters of this explicit expression and
      the preferred spike train pattern of the synapse. In particular, our analysis of
      the transmission of modulated pulse trains across a dynamic synapse links the
      original parameters of the quantal model to the transmission efficacy of two
      major spiking regimes, that is, bursting and constant-rate ones.

PMID- 19584939
TI  - Changes in EEG power spectral density and cortical connectivity in healthy and
      tetraplegic patients during a motor imagery task.
AB  - Knowledge of brain connectivity is an important aspect of modern neuroscience, to
      understand how the brain realizes its functions. In this work, neural mass models
      including four groups of excitatory and inhibitory neurons are used to estimate
      the connectivity among three cortical regions of interests (ROIs) during a foot
      movement task. Real data were obtained via high-resolution scalp EEGs on two
      populations: healthy volunteers and tetraplegic patients. A 3-shell Boundary
      Element Model of the head was used to estimate the cortical current density and
      to derive cortical EEGs in the three ROIs. The model assumes that each ROI can
      generate an intrinsic rhythm in the beta range, and receives rhythms in the alpha
      and gamma ranges from other two regions. Connectivity strengths among the ROIs
      were estimated by means of an original genetic algorithm that tries to minimize
      several cost functions of the difference between real and model power spectral
      densities. Results show that the stronger connections are those from the
      cingulate cortex to the primary and supplementary motor areas, thus emphasizing
      the pivotal role played by the CMA_L during the task. Tetraplegic patients
      exhibit higher connectivity strength on average, with significant statistical
      differences in some connections. The results are commented and virtues and
      limitations of the proposed method discussed.

PMID- 19584942
TI  - Sequence characterization of the MC1R gene in yak (Poephagus grunniens) breeds
      with different coat colors.
AB  - Melanocortin 1 receptor (MC1R) gene plays a key role in determining coat color in
      several species, including the cattle. However, up to now there is no report
      regarding the MC1R gene and the potential association of its mutations with coat
      colors in yak (Poephagus grunniens). In this study, we sequenced the encoding
      region of the MC1R gene in three yak breeds with completely white (Tianzhu breed)
      or black coat color (Jiulong and Maiwa breeds). The predicted coding region of
      the yak MC1R gene resulted of 954 bp, the same to that of the wild-type cattle
      sequence, with >99% identity. None of the mutation events reported in cattle was
      found. Comparing the yak obtained sequences, five nucleotide substitutions were
      detected, which defined three haplotypes (E(Y1), E(Y2), and E(Y3)). Of the five
      mutations, two, characterizing the E(Y1) haplotype, were nonsynonymous
      substitutions (c.340C>A and c.871G>A) causing amino acid changes located in the
      first extracellular loop (p.Q114K) and in the seventh transmembrane region
      (p.A291T). In silico prediction might indicate a functional effect of the latter
      substitution. However, all three haplotypes were present in the three yak breeds
      with relatively consistent frequency distribution, despite of their distinguished
      coat colors, which suggested that there was no across-breed association between
      haplotypes or genotypes and black/white phenotypes, at least in the investigated
      breeds. Other genes may be involved in affecting coat color in the analyzed yaks.

PMID- 19584941
TI  - Rapid Diagnosis of Intestinal Parasitic Protozoa, with a Focus on Entamoeba
      histolytica.
AB  - Entamoeba histolytica is an invasive intestinal pathogenic parasitic protozoan
      that causes amebiasis. It must be distinguished from Entamoeba dispar and E.
      moshkovskii, nonpathogenic commensal parasites of the human gut lumen that are
      morphologically identical to E. histolytica. Detection of specific E. histolytica
      antigens in stools is a fast, sensitive technique that should be considered as
      the method of choice. Stool real-time PCR is a highly sensitive and specific
      technique but its high cost make it unsuitable for use in endemic areas where
      there are economic constraints. Serology is an important component of the
      diagnosis of intestinal and especially extraintestinal amebiasis as it is a
      sensitive test that complements the detection of the parasite antigens or DNA.
      Circulating Gal/GalNac lectin antigens can be detected in the serum of patients
      with untreated amoebic liver abscess. On the horizon are multiplex real-time PCR
      assays which permit the identification of multiple enteropathogens with high
      sensitivity and specificity.

PMID- 19584944
TI  - A model of postural control in quiet standing: robust compensation of delay
      induced instability using intermittent activation of feedback control.
AB  - The main purpose of this study is to compare two different feedback controllers
      for the stabilization of quiet standing in humans, taking into account that the
      intrinsic ankle stiffness is insufficient and that there is a large delay
      inducing instability in the feedback loop: 1) a standard linear, continuous-time
      PD controller and 2) an intermittent PD controller characterized by a switching
      function defined in the phase plane, with or without a dead zone around the
      nominal equilibrium state. The stability analysis of the first controller is
      carried out by using the standard tools of linear control systems, whereas the
      analysis of the intermittent controllers is based on the use of Poincare maps
      defined in the phase plane. When the PD-control is off, the dynamics of the
      system is characterized by a saddle-like equilibrium, with a stable and an
      unstable manifold. The switching function of the intermittent controller is
      implemented in such a way that PD-control is 'off' when the state vector is near
      the stable manifold of the saddle and is 'on' otherwise. A theoretical analysis
      and a related simulation study show that the intermittent control model is much
      more robust than the standard model because the size of the region in the
      parameter space of the feedback control gains (P vs. D) that characterizes stable
      behavior is much larger in the latter case than in the former one. Moreover, the
      intermittent controller can use feedback parameters that are much smaller than
      the standard model. Typical sway patterns generated by the intermittent
      controller are the result of an alternation between slow motion along the stable
      manifold of the saddle, when the PD-control is off, and spiral motion away from
      the upright equilibrium determined by the activation of the PD-control with low
      feedback gains. Remarkably, overall dynamic stability can be achieved by
      combining in a smart way two unstable regimes: a saddle and an unstable spiral.
      The intermittent controller exploits the stabilizing effect of one part of the
      saddle, letting the system evolve by alone when it slides on or near the stable
      manifold; when the state vector enters the strongly unstable part of the saddle
      it switches on a mild feedback which is not supposed to impose a strict stable
      regime but rather to mitigate the impending fall. The presence of a dead zone in
      the intermittent controller does not alter the stability properties but improves
      the similarity with biological sway patterns. The two types of controllers are
      also compared in the frequency domain by considering the power spectral density
      (PSD) of the sway sequences generated by the models with additive noise.
      Different from the standard continuous model, whose PSD function is similar to an
      over-damped second order system without a resonance, the intermittent control
      model is capable to exhibit the two power law scaling regimes that are typical of
      physiological sway movements in humans.

PMID- 19584945
TI  - Analysis of skeletal phenotypes in thyroid hormone receptor mutant mice.

PMID- 19584943
TI  - Trichomonas vaginalis infection and associated risk factors in a socially
      marginalized female population in coastal Peru.
AB  - OBJECTIVE: The epidemiology of Trichomonas vaginalis infection among sexually
      active socially-marginalized women in three urban, coastal Peruvian cities was
      examined in order to quantify the prevalence of trichomonas infection and
      identify associated risk factors. METHODS: We conducted a cross-sectional, venue
      based study of women from socially-marginalized populations in three coastal
      Peruvian cities. RESULTS: Among the 319 women enrolled, the overall prevalence of
      trichomonal infection was 9.1% (95% CI, 5.9%-12.3%). The mean age was 26.3 years,
      and 35.5% reported having had unprotected intercourse with nonprimary partners
      and 19.8% reported two or more sex partners in the last three months. Trichomonal
      infection was associated with increased number of sex partners (PR 2.5, 95% CI
      1.4-4.6) and unprotected sex with nonprimary partner in the last three months (PR
      2.3, 95% CI 1.1-4.9). CONCLUSIONS: A moderately high prevalence of trichomonal
      infection was found among women in our study. Trichomonal infection was
      associated with unprotected sex and multiple sex partners. Efforts to control the
      continued spread of trichomonal infection are warranted.

PMID- 19584946
TI  - Spatio-temporal modeling of chronic PM10 exposure for the Nurses' Health Study.
AB  - Chronic epidemiological studies of airborne particulate matter (PM) have
      typically characterized the chronic PM exposures of their study populations using
      city- or countywide ambient concentrations, which limit the studies to areas
      where nearby monitoring data are available and which ignore within-city spatial
      gradients in ambient PM concentrations. To provide more spatially refined and
      precise chronic exposure measures, we used a Geographic Information System (GIS)
      based spatial smoothing model to predict monthly outdoor PM(10) concentrations in
      the northeastern and midwestern United States. This model included monthly smooth
      spatial terms and smooth regression terms of GIS-derived and meteorological
      predictors. Using cross-validation and other pre-specified selection criteria,
      terms for distance to road by road class, urban land use, block group and county
      population density, point- and area-source PM(10) emissions, elevation, wind
      speed, and precipitation were found to be important determinants of PM(10)
      concentrations and were included in the final model. Final model performance was
      strong (cross-validation R(2)=0.62), with little bias (-0.4 mug m(-3)) and high
      precision (6.4 mug m(-3)). The final model (with monthly spatial terms) performed
      better than a model with seasonal spatial terms (cross-validation R(2)=0.54). The
      addition of GIS-derived and meteorological predictors improved predictive
      performance over spatial smoothing (cross-validation R(2)=0.51) or inverse
      distance weighted interpolation (cross-validation R(2)=0.29) methods alone and
      increased the spatial resolution of predictions. The model performed well in both
      rural and urban areas, across seasons, and across the entire time period. The
      strong model performance demonstrates its suitability as a means to estimate
      individual-specific chronic PM(10) exposures for large populations.

PMID- 19584947
TI  - Resonance tuning of a neuromechanical system with two negative sensory feedback
      configurations.
AB  - Resonance tuning in a model of rhythmic movement is compared when the central
      pattern generator (CPG) consists of two endogenously bursting or two tonically
      spiking neurons that are connected with reciprocally inhibitory synapses. The CPG
      receives inhibitory and/or excitatory position feedback from a linear, one-degree
      of-freedom mechanical subsystem. As with previously published results [5, 15],
      resonance tuning is limited to frequencies that are greater than the intrinsic
      CPG frequency with endogenously bursting neurons. In contrast, with tonically
      spiking neurons, the resonance tuning range is expanded to frequencies that are
      below the intrinsic CPG frequency.

PMID- 19584948
TI  - Mere Exposure and Racial Prejudice: Exposure to Other-Race Faces Increases Liking
      for Strangers of That Race.
AB  - White participants were exposed to other-race or own-race faces to test the
      generalized mere exposure hypothesis in the domain of face perception, namely
      that exposure to a set of faces yields increased liking for similar faces that
      have never been seen. In Experiment 1, rapid supraliminal exposures to Asian
      faces increased White participants' subsequent liking for a different set of
      Asian faces. In Experiment 2, subliminal exposures to Black faces increased White
      participants' subsequent liking for a different set of Black faces. The findings
      are consistent with prominent explanations for mere exposure effects as well as
      with the familiar face overgeneralization hypothesis that prejudice derives in
      part from negative reactions to faces that deviate from the familiar own-race
      prototype.

PMID- 19584949
TI  - Nanopore with Transverse Nanoelectrodes for Electrical Characterization and
      Sequencing of DNA.
AB  - A DNA sequencing device which integrates transverse conducting electrodes for the
      measurement of electrode currents during DNA translocation through a nanopore has
      been nanofabricated and characterized. A focused electron beam (FEB) milling
      technique, capable of creating features on the order of 1 nm in diameter, was
      used to create the nanopore. The device was characterized electrically using gold
      nanoparticles as an artificial analyte with both DC and AC measurement methods.
      Single nanoparticle/electrode interaction events were recorded. A low-noise, high
      speed transimpedance current amplifier for the detection of nano to picoampere
      currents at microsecond time scales was designed, fabricated and tested for
      future integration with the nanopore device.

PMID- 19584950
TI  - Predictors of Infant Feeding Frequency by Mexican Immigrant Mothers.
AB  - With an increase in the prevalence of overweight being seen as early as infancy,
      it is essential that the factors which account for early excess weight gain be
      identified. In this study, maternal and infant characteristics were examined to
      determine their relation to the frequency of infants being fed. A cohort of 67
      low-educated Mexican mothers who formula-fed their infants were recruited at a
      WIC Center and home-visited when their infants were 6-months-old. Mothers were
      surveyed with regard to their feeding attitudes and perception of their infant's
      temperament, and kept a 24-hour diary of their infant's behavior. Nearly 30% of
      the 6-month-old infants were at or above the 85(th) percentile of weight-for
      length. A regression analysis revealed only one factor, the number of infant
      crying episodes, as predictive of infant feeding (Beta = .246, p<.07), with the
      correlation even stronger (r =.35 (p<.01). As crying appeared to elicit feeding
      among these mothers, pediatricians, nurses, and WIC educators should consider
      discussing alternate strategies for quieting infants with the mothers they
      counsel.

PMID- 19584951
TI  - Immune responses in autoimmune hepatitis: effect of prednisone and azathioprine
      treatment: case report.
AB  - The role of the immune response in autoimmune hepatitis has not been studied
      before and after prednisone and azathioprine treatment. Distributions of blood
      lymphocytes (CD4+, CD8+, CD19+, CD23+, CD16/56+), levels of serum immunoglobulins
      (IgM, IgG, IgE, IgA) and cytokines (IFN-gamma, IL-4, IL-12, TNFalpha ) were
      studied in a child (f/14 y/o) with autoimmune hepatitis before and after
      prednisone (20 mg/d) and azathioprine (50 mg/d) treatment (nephelometry, UniCAP
      Total IgE Fluoroenzymeimmunoassay, flow cytometry, cytokine ELISA). Patient was
      studied for 0-2.5 yrs; treatment was initiated 12 weeks post diagnosis. Numbers
      of CD4+ T cells increased (50%), while CD19+ and CD23+ cells decreased (>50%)
      post treatment; other lymphocyte subsets were unaffected by treatment. Serum IgG
      and IgE levels decreased (>50%) after treatment; serum IgM and IgA were within
      normal range and were not affected by treatment High levels of IFN-gamma (5-23
      pg/ml) were initially detected in serum, which decreased after treatment (<0.1
      pg/ml). Furthermore, low levels of IL-4 (0.2 pg/mL) were detected before
      treatment, which were not detected after treatment (<0.1 pg/ml). In contrast,
      before treatment, IL-12 and TNFalpha were not detected in serum; however after
      treatment the levels of IL-12 and TNFalpha dramatically increased. Prednisone and
      azathioprine treatment decreased total serum IgG, IgE, IFN-gamma and IL-4 levels,
      and blood CD19+ and CD23+ cells; however serum IL-12, TNFalpha and blood CD4+ T
      cells increased with treatment. Understanding immunomodulation in autoimmune
      hepatitis will provide better insight and mechanisms of this disease and may
      tailor more effective therapeutic intervention.

PMID- 19584952
TI  - Comparison of skeletal muscle strength between cardiac patients and age-matched
      healthy controls.
AB  - The purpose of the present study was to compare muscular strength of knee
      extensors and arm flexor muscles of cardiac patients (n = 638) and healthy
      controls (n = 961) in different age groups. Isometric torques were measured in a
      sitting position with the elbow, hip, and knee flexed to 90(0). For statistical
      analysis, age groups were pooled in decades from the age of 30 to 90 years.
      Additionally, the influence of physical lifestyle prior to disease on muscular
      strength was obtained in the patients. For statistical analysis three-way ANOVA
      (factors age, gender, and physical activity level) was used.Both in patients and
      in controls a significant age-dependent decline in maximal torque could be
      observed for arm flexors and knee extensors. Maximal leg extensor muscle showed
      statistically significant differences between healthy controls and cardiac
      patients as well as between subgroups of patients: Physically inactive patients
      showed lowest torques (male: 148 +/- 18 Nm; female: 82 +/- 25 Nm) while highest
      values were measured in control subjects (male: 167 +/- 16 Nm; female: 93 +/- 17
      Nm). In contrast, arm flexor muscles did not show any significant influence of
      health status or sports history.This qualitative difference between weight
      bearing leg muscles and the muscle group of the upper extremity suggest that
      lower skeletal muscle strength in heart patients is mainly a consequence of
      selective disuse of leg muscles rather than any pathological skeletal muscle
      metabolism. Since a certain level of skeletal muscle strength is a prerequisite
      to cope with everyday activities, strength training is recommended as an
      important part of cardiac rehabilitation.

PMID- 19584953
TI  - How subchronic and chronic health effects can be neglected for GMOs, pesticides
      or chemicals.
AB  - Chronic health effects are increasing in the world such as cancers, hormonal,
      reproductive, nervous, or immune diseases, even in young people. During
      regulatory toxicological subchronic tests to prevent these on mammalian health,
      prior commercialization of chemicals, including pesticides and drugs, or GMOs,
      some statistically significant findings may be revealed. This discussion is about
      the need to investigate the relevant criteria to consider those as biologically
      significant. The sex differences and the non linear dose or time related effects
      should be considered in contrast to the claims of a Monsanto-supported expert
      panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in
      particular to reveal hormone-dependent diseases and first signs of toxicities.

PMID- 19584954
TI  - Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on
      the liver of male albino rats.
AB  - Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different
      chemical classes, have been extensively used for chemotherapy of various cancers.
      Despite extensive investigations into their hepatotoxicity, there is very limited
      information on their effects on the structure and ultra-structure of liver cells
      in vivo. Here, we demonstrate for the first time, the effects of these three
      anticancer drugs on rat liver toxicity using both light and electron microscopy.
      Light microscopic observations revealed that higher doses of cisplatin and
      doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including
      dissolution of hepatic cords, focal inflammation and necrotic tissues.
      Interestingly, low doses also exhibited abnormal changes, including periportal
      fibrosis, degeneration of hepatic cords and increased apoptosis. These changes
      were confirmed at ultrastructural level, including vesiculated rough endoplasmic
      reticulum and atrophied mitochondria with ill-differentiated cisternae, dense
      collection of macrophages and lymphocytes as well as fibrocytes with collagenous
      fibrils manifesting early sign of fibrosis, especially in response to cisplatin
      and doxorubicin -treatment. Our results provide in vivo evidence, at
      ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin
      and 5-FU at both light and electron microscopi. These results can guide the
      design of appropriate treatment regimen to reduce the hepatotoxic effects of
      these anticancer drugs.

PMID- 19584956
TI  - "A form of practical machinery": the origins of Research Ethics Committees in the
      UK, 1967-1972.

PMID- 19584957
TI  - Popularizing controversial science: a popular treatise on poisons by Mateu Orfila
      (1818).

PMID- 19584958
TI  - Procuring corpses: the English anatomy inspectorate, 1842 to 1858.

PMID- 19584955
TI  - Lipoproteins, cholesterol homeostasis and cardiac health.
AB  - Cholesterol is an essential substance involved in many functions, such as
      maintaining cell membranes, manufacturing vitamin D on surface of the skin,
      producing hormones, and possibly helping cell connections in the brain. When
      cholesterol levels rise in the blood, they can, however, have dangerous
      consequences. In particular, cholesterol has generated considerable notoriety for
      its causative role in atherosclerosis, the leading cause of death in developed
      countries around the world. Homeostasis of cholesterol is centered on the
      metabolism of lipoproteins, which mediate transport of the lipid to and from
      tissues. As a synopsis of the major events and proteins that manage lipoprotein
      homeostasis, this review contributes to the substantial attention that has
      recently been directed to this area. Despite intense scrutiny, the majority of
      phenotypic variation in total cholesterol and related traits eludes explanation
      by current genetic knowledge. This is somewhat disappointing considering
      heritability estimates have established these traits as highly genetic. Thus, the
      continued search for candidate genes, mutations, and mechanisms is vital to our
      understanding of heart disease at the molecular level. Furthermore, as marker
      development continues to predict risk of vascular illness, this knowledge has the
      potential to revolutionize treatment of this leading human disease.

PMID- 19584959
TI  - Holy medicine and diseases of the soul: Henry of Lancaster and Le livre de seyntz
      medicines.

PMID- 19584960
TI  - The English sweat in Lubeck and North Germany, 1529.

PMID- 19584961
TI  - A newly discovered manuscript dedication by Mark Akenside.

PMID- 19584962
TI  - Nalfurafine hydrochloride: a new drug for the treatment of uremic pruritus in
      hemodialysis patients.
AB  - Uremic pruritus in hemodialysis patients is intractable and no effective
      treatments have been established yet. Although the precise mechanism of the
      pruritus is still unclear, accumulating evidence suggests that activation of the
      micro-opioid receptors may induce pruritus in hemodialysis patients. On the other
      hand, activation of kappa-opioid receptors is known to control or inhibit the
      signals activated through micro-opioid receptors; therefore, it was expected that
      kappa-opioid receptor agonists would be able to reduce pruritus in patients
      undergoing hemodialysis. Nalfurafine hydrochloride is a novel derivative of the
      opioid receptor antagonist naltrexone. Nalfurafine hydrochloride is a selective
      kappa-opioid receptor agonist and has a potent antipruritic effect on various
      types of pruritus through central kappa-opioid receptor activation in non
      clinical pharmacological studies. Moreover, clinical studies have demonstrated
      that nalfurafine hydrochloride possesses efficacy and safety in hemodialysis
      patients with uremic pruritus. In this review, we provide a detailed description
      of the activity of nalfurafine hydrochloride using published data of in vitro, in
      vivo nonclinical pharmacological and clinical studies in hemodialysis patients
      with uremic pruritus.

PMID- 19584963
TI  - Clevudine for hepatitis B.
AB  - Clevudine is distinguished from other oral agents by its sustained suppression of
      HBV DNA for several months after cessation of therapy, according to a
      comprehensive review of hepatitis B in the 2 October 2008 issue of the New
      England Journal of Medicine. Clevudine is differentiated by i) an unusual
      activation pathway to the biochemically active triphosphate; ii) a mechanism of
      action of clevudine triphosphate that inhibits multiple steps of the hepatitis B
      virus (HBV) intracellular life cycle; iii) a long half-life and iv) significant
      reduction of covalently closed circular DNA (cccDNA) in animal models. Clevudine
      was approved and is marketed in South Korea based on two 24-week phase III trials
      vs. placebo. In these studies with treatment-naive patients, 59% of 248 HBeAg
      positive patients had undetectable HBV DNA after 24 weeks of treatment compared
      with 92% of 89 HBeAg-negative patients, while the percentage of patients with
      normal liver enzymes was 68% in the HBeAg-positive patients and 75% in the HBeAg
      negative patients (all statistically significant versus placebo). Follow-up
      studies include trials vs. lamivudine as well as a phase IV study of long-term
      clevudine. Larger and longer phase III trials in the United States, European
      Union, Asia and South America of clevudine vs. adefovir are ongoing. An ANRS
      sponsored trial of clevudine vs. tenofovir vs. the combination of the two agents
      is poised to begin. Literature published through November 2008 and presentations
      from the 59th annual meeting of the American Association for the Study of Liver
      Diseases held 31 October to 4 November 2008 are included.

PMID- 19584964
TI  - Sertraline in the treatment of panic disorder.
AB  - Sertraline has been used as a treatment for anxiety disorders since the mid 1990s
      and has proven itself an effective, well-tolerated and economically viable
      treatment for panic disorder (PD) when used in the range of 50 to 175 mg per day.
      Numerous short- and long-term studies have demonstrated the efficacy of
      sertraline in the treatment of PD. In addition, in an 80-week relapse prevention
      trial, sertraline was found to reduce severity and frequency of panic attacks,
      baseline anxiety and to confer protection from relapse for up to 36 weeks
      following withdrawal from medication Data on sertraline as an alternative to
      tricyclic antidepressants and paroxetine in terms of tolerability is presented
      here. The efficacy of sertraline is shown to be comparable to cognitive
      behavioral therapy in one study and recent attempts at adjunctive therapy for PD
      with atypical antipsychotics are reviewed as well. Anxiety disorders constitute
      the most prevalent grouping of mental illnesses in the general population.
      Patients with panic disorder suffer a significant degree of medical comorbidity
      in addition to overlap with major depressive disorder, generalized anxiety
      disorder and somatization disorders. Further, PD patients experience a high
      degree of debility as measured by public assistance, emergency room and medical
      service utilization and suicide risk. Epidemiological data and studies linking
      significant decrease in medical, emergency service and laboratory utilization in
      PD patients taking sertraline are also presented. When reviewed in context with
      the efficacy trials, a compelling argument can be made for making sertraline a
      first choice among the serotonin reuptake inhibitors in the treatment of PD.

PMID- 19584965
TI  - Allopurinol, an inhibitor of uric acid synthesis--can it be used for the
      treatment of metabolic syndrome and related disorders?
AB  - Allopurinol is an inhibitor of xanthine oxidoreductase (XOR) and inhibits the
      generation of uric acid (UA) as the final product of purine catabolism, as well
      as the resulting generation of superoxide (O2(-)), in humans. Elevation of the
      serum UA (SUA) level, referred to as hyperuricemia (HU), eventually leads to gout
      and allopurinol has been used for the treatment of HU and gout. Studies have
      revealed the role of elevated SUA levels and the associated oxidative stress (OS)
      in a broad spectrum of pathological conditions and it is anticipated that these
      findings would also expand the use of allopurinol as a therapeutic drug. This
      article presents a review of reports, mainly of recent studies, on the efficacy
      of allopurinol in various diseases and explores novel potential uses of the drug.
      Important novel and potential uses of great interest include metabolic syndrome
      (MetS) and related disorders, chronic kidney disease (CKD), nonalcoholic fatty
      liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Ischemia
      reperfusion injury and mucositis, encountered as adverse effects of cancer
      treatment, have also been under investigation as potential targets for
      allopurinol.

PMID- 19584966
TI  - Empiric antibiotic selection for infectious emergencies: bacterial pneumonia,
      meningitis and sepsis.
AB  - Appropriate early management of infectious emergencies is essential to preventing
      adverse outcomes. Clinicians in acute-care settings must be prepared to provide
      appropriate empiric antibiotics, as failure to do so has been associated with an
      increased risk of mortality. Empiric treatment of these infections requires
      knowledge of the disease state, most common pathogens, and patient-specific risk
      factors. Additionally, regional and institutional patterns of antibiotic
      resistance must be taken into consideration. At the same time, inappropriate use
      of broad-spectrum antibiotics should be avoided to prevent emergence of
      antimicrobial resistance. It is also essential that initial antibiotic therapy be
      de-escalated and redirected once the causative pathogen has been identified and
      antibiotic susceptibilities determined. Bacterial infection with pneumonia,
      meningitis and sepsis severe enough to warrant hospitalization are included in
      this review. The most common bacterial pathogens and empiric antibiotic
      recommendations for immunocompetent adults will be discussed. In addition,
      circumstances that may influence the selection of certain antibiotics are
      reviewed.

PMID- 19584967
TI  - Novel zolpidem formulations.
AB  - Zolpidem is currently the global market leader in the hypnotic arena. Recently
      several novel zolpidem formulations have been launched in the U.S. or are in the
      preregistration development phase. These comprise an extended-release form, two
      types of sublingual formulations and an oral spray. The pharmacokinetic and
      pharmacodynamic effects of these formulations are reviewed.

PMID- 19584968
TI  - Recommendations for advancing the care of Canadians living with refractory angina
      pectoris: a Canadian Cardiovascular Society position statement.

PMID- 19584969
TI  - Formation of a national network for rapid response to device and lead advisories:
      The Canadian Heart Rhythm Society Device Advisory Committee.
AB  - The Canadian Heart Rhythm Society (CHRS) Device Advisory Committee was
      commissioned to respond to advisories regarding cardiac rhythm device and lead
      performance on behalf of the CHRS. In the event of an advisory, the Chair uses an
      e-mail network to disseminate advisory information to Committee members broadly
      representative of the Canadian device community. A consensus recommendation is
      prepared by the Committee and made available to all Canadian centres on the CHRS
      Web site after approval by the CHRS executive. This collaborative approach using
      an e-mail network has proven very efficient in providing a rapid national
      response to device advisories. The network is an ideal tool to collect specific
      data on implanted device system performance and allows for prompt reporting of
      clinically relevant data to front-line clinicians and patients.

PMID- 19584970
TI  - Diagnostic usefulness of graded exercise testing in pediatric supraventricular
      tachycardia.
AB  - BACKGROUND: Episodic symptoms, often reported during exertion, complicate the
      assessment of suspected supraventricular tachycardia (SVT). OBJECTIVE: To examine
      the diagnostic sensitivity of graded exercise testing in young patients with
      documented SVT or ventricular preexcitation. METHODS: A single-centre
      retrospective review identified 53 patients (5.1 to 17.5 years of age) with
      structurally normal hearts who had undergone 65 graded treadmill exercise tests
      in the setting of either documented SVT with normal resting electrocardiograms
      (n=30) or ventricular preexcitation (n=23). Twenty-five patients (13 pre-excited
      and 12 nonpreexcited) had exercise-related symptoms. SVT induction during
      exercise testing was assessed in relation to pre-excitation and the patient's
      history of exercise-induced symptoms. RESULTS: SVT was induced during six of the
      65 exercise tests performed in three of 53 patients (overall sensitivity 5.7%).
      All three patients had a history of exercise- induced symptoms, and two had
      ventricular preexcitation. SVT was induced in 12% of patients with exercise-
      related symptoms. No other rhythm disturbances occurred during exercise testing.
      CONCLUSION: The diagnostic yield of graded exercise testing in patients with
      suspected SVT is limited, even among those with exercise related symptoms.

PMID- 19584971
TI  - Impact of the metabolic syndrome on aortic pulse pressure and ascending aortic
      pulsatility in patients with angiographically normal coronary arteries.
AB  - BACKGROUND: Large artery stiffness is a major determinant of pulse pressure (PP),
      and PP at baseline has been associated with future coronary events. OBJECTIVE: To
      evaluate the impact of the metabolic syndrome on aortic PP and ascending aortic
      pulsatility (AP) in patients with angiographically normal coronary arteries.
      METHODS: Forty-two patients with the metabolic syndrome and 40 age matched
      control subjects without the metabolic syndrome were included in the study. All
      subjects had normal coronary arteries. Diagnosis of the metabolic syndrome was
      based on the International Diabetes Federation guidelines published in 2005.
      Ascending AP was estimated as the ratio of aortic PP to mean blood pressure.
      RESULTS: Aortic PP (59+/-12 mmHg versus 43+/-10 mmHg; P<0.001) and ascending AP
      (0.54+/-0.10 versus 0.48+/-0.10; P<0.001) were significantly higher in the
      metabolic syndrome group. Multiple regression analysis revealed statistically
      independent relationships between ascending AP and fasting blood glucose, waist
      circumference and systolic blood pressure (model R2=0.408; P<0.001). The
      metabolic syndrome, as a whole, was also independently associated with both
      ascending AP (P<0.01) and aortic PP (P<0.01). CONCLUSION: The data showed that
      the metabolic syndrome is independently associated with increased aortic PP and
      ascending AP in patients with normal coronary arteries, suggesting aortic
      stiffness as one of the possible mechanisms underlying the excess cardiovascular
      risk associated with the metabolic syndrome.

PMID- 19584972
TI  - Alteration of messenger RNA and protein levels of cardiac alpha(1)-adrenergic
      receptor and angiotensin II receptor subtypes during aging in rats.
AB  - BACKGROUND: Structural and functional alterations in the senescent heart have
      been associated with an activated sympathetic nervous system and a regional
      cardiac renin-angiotensin system. To date, however, limited information related
      to their expression alteration during the whole procress of growth and
      development has been reported. OBJECTIVES: To examine the expression of alpha(1)
      adrenergic receptor (alpha(1)-AR) and angiotensin II receptor (ATR) subtypes in
      the left ventricle of hearts from young adult, middle-aged, presenescent and
      senescent rats. METHODS: Semiquantitative reverse transcriptase polymerase chain
      reaction and Western blot were used to quantitate the messenger RNA and protein
      of alpha(1)-AR and ATR subtypes, respectively, in the left ventricles of three-
      (young adult), 12- (middle age), 18- (presenescent) and 24-month-old (senescent)
      Wistar rats. RESULTS AND CONCLUSIONS: alpha(1A)-AR expression decreased gradually
      with age, and alpha(1D)-AR expression was repressed in middle age and
      presenescence, while the expression of alpha(1B)-AR remained unchanged during
      senescence. AT(1)R expression was unaffected by aging from young adulthood to
      presenescence, but exhibited a remarkable upregulation in senescence. There were
      no significant discrepancies of cardiac AT(2)R expression among the four age
      groups, but both messenger RNA and protein had a tendency to upregulate during
      aging. The results suggest that there are considerable changes of expression of
      cardiac alpha(1)-AR and ATR subtypes during growth and development. The change of
      cardiac alpha(1)-AR and ATR expression during aging is a protective response to
      senescence by keeping normal myocardial contractility, while the upregulation of
      AT(1)R and AT(2)R promotes age-related myocardium hypertrophy and cardiac
      remodelling.

PMID- 19584974
TI  - Bivalirudin as an anticoagulant for simultaneous integrated coronary artery
      revascularization - a novel approach to an inherent concern.
AB  - BACKGROUND: Simultaneous integrated coronary artery revascularization combines
      coronary artery bypass surgery and percutaneous coronary intervention into a
      single procedure. This approach provides immediate, complete and optimal
      myocardial revascularization in a less invasive manner. Because simultaneous
      integrated coronary revascularization necessitates two distinct anticoagulation
      protocols for the surgical and percutaneous aspects of the procedure, combining
      these anticoagulation protocols carries a bleeding risk. Using a single
      anticoagulant to facilitate the necessities of both aspects of the integrated
      approach may alleviate this risk. CASE PRESENTATION: A 45-year-old man with an
      occluded left anterior descending artery and a moderately stenotic circumflex
      artery underwent simultaneous integrated coronary revascularization. Bivalirudin
      was used to achieve anticoagulation for the duration of the procedure. The
      patient was asymptomatic with excellent patency of both the bypass graft and the
      stented circumflex artery via angiography at 10 months. CONCLUSION: Bivalirudin
      can be used to effectively achieve a unified anticoagulation protocol for
      simultaneous integrated revascularization.

PMID- 19584973
TI  - Amiodarone-induced thyrotoxicosis: a review.
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) develops in 3% of amiodarone
      treated patients in North America. AIT is classified as type 1 or type 2. Type 1
      AIT occurs in patients with underlying thyroid pathology such as autonomous
      nodular goiter or Graves' disease. Type 2 AIT is a result of amiodarone causing a
      subacute thyroiditis with release of preformed thyroid hormones into the
      circulation. OBJECTIVES: To review the literature and present an overview of the
      differentiation between and management of type 1 and type 2 AIT. METHODS: PubMed,
      the Cumulative Index to Nursing and Allied Health Literature and Medscape
      searches of all available English language articles from 1983 to 2006 were
      performed. Search terms included 'amiodarone -induced thyrotoxicosis',
      'complications', 'management', 'treatment' and 'colour flow Dopper sonography'.
      RESULTS: There is evidence to suggest that to differentiate between type 1 and
      type 2 AIT, a careful history and physical examination should be performed to
      identify pre-existing thyroid disease. An iodine-131 uptake test and colour flow
      Doppler sonography should be performed. Patients with type 2 AIT should receive a
      trial of glucocorticoids, whereas those with type 1 should receive antithyroid
      therapy. For patients in whom the mechanism of the thyrotoxicosis is unclear, a
      combination of prednisone and antithyroid therapy may be considered.

PMID- 19584975
TI  - An unusual case of infective endocarditis: extension of a tricuspid valve
      vegetation into the left atrium through a patent foramen ovale.
AB  - Tricuspid valve endocarditis frequently occurs in the setting of intravenous drug
      use. A case of tricuspid valve endocarditis in a 37-year-old woman with a history
      of intravenous cocaine use is described. Transthoracic echocardiography showed
      extension of the tricuspid valve mass through a patent foramen ovale and into the
      left atrium. One week after intravenous antibiotic treatment, the mass no longer
      traversed the patent foramen ovale, and only two smaller tricuspid valve
      vegetations remained. The present case demonstrates the value of performing a
      complete and thorough transthoracic echocardiography to visualize and evaluate
      both the right- and left-sided consequences of infective endocarditis in
      intravenous drug users. It also serves as a useful reminder to physicians caring
      for such patients that right sided endocarditis can have important left-sided
      complications.

PMID- 19584977
TI  - Assessment of activity status and survival according to the Canadian
      Cardiovascular Society angina classification.
AB  - BACKGROUND: Despite its widespread use, limited data on the validity of the
      Canadian Cardiovascular Society angina (CCSA) classification relative to other
      measures of functional status have been reported. OBJECTIVE: To assess the
      validity of the CCSA classification by comparing it with the Duke Activity Status
      Index (DASI) and evaluate its prognostic significance with respect to long-term
      mortality. METHODS: The study population consisted of 1407 patients who underwent
      cardiac catheterization between 1992 and 1996. The median follow-up period was
      9.7 years (interquartile range 6.1 to 11.1 years) and the mortality status as of
      December 31, 2004 was available for all patients. RESULTS: The first three CCSA
      classes were inversely related to the DASI. The mean (+/- SD) scores were as
      follows: class I, 31.4+/-16.7; class II, 22.5+/-15.4; class III, 14.7+/-14.3; and
      class IV, 15.5+/-14.9 (P<0.01). Increasing CCSA class was associated with
      increased long-term mortality, even after adjusting for baseline characteristics.
      Chest pain course was also an important modulator of mortality among class III
      and IV patients; one-year mortality rates were 8.1% among unstable patients
      compared with 4.8% among patients with stable or progressing course. CONCLUSION:
      CCSA classes I to III were inversely related to DASI scores and linearly
      associated with mortality. The similarity in outcomes among class III and IV
      patients is probably explained by the confounding effect of the stability of the
      patients' symptoms. The higher mortality risk among class III and IV patients
      with an unstable course provides impetus for a revised CCSA definition
      incorporating this information.

PMID- 19584976
TI  - Prognostic value of treadmill exercise and dobutamine stress positron emission
      tomography.
AB  - BACKGROUND: Although positron emission tomography (PET) is routinely performed
      using vasodilator stress, exercise and dobutamine stress are available
      alternatives. Evidence suggests that vasodilator PET myocardial perfusion imaging
      (MPI) has prognostic value, but the prognostic value of treadmill exercise and
      dobutamine PET MPI is unknown. OBJECTIVE: To determine the potential prognostic
      value of nonvasodilator stress PET MPI. METHODS: Patients underwent treadmill
      exercise or dobutamine PET MPI. Images were assessed qualitatively and
      semiquantitatively. PET results were categorized as normal (summed stress score
      [SSS] of less than 4), abnormal (SSS of 4 or greater) or inconclusive (SSS of
      less than 4 and submaximal peak stress heart rate). Patient follow-up (cardiac
      death, nonfatal myocardial infarction [MI] and/or late revascularization) was
      performed. RESULTS: Of the 124 patients (mean follow-up period of 2.3+/-1.6
      years), 46 patients (37%) had a normal study, 15 patients (12%) had an
      inconclusive study and 63 (51%) had an abnormal PET. Patients with a normal PET
      had no deaths or nonfatal MI. One patient with a normal PET underwent late
      revascularization (annual event rate of 1.7%). Patients with an abnormal PET had
      15 cardiac events (one cardiac death, four nonfatal MIs and 10 late
      revascularizations), with an annual event rate of 13.0% (P=0.002). CONCLUSIONS:
      Although small, the present study suggests that defects seen on PET myocardial
      perfusion, resulting from stressors (treadmill exercise and dobutamine) that
      increase myocardial oxygen demand, may have prognostic value.

PMID- 19584978
TI  - Multiple imputation for missing with cardiac magnetic resonance imaging data:
      results from the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Cardiac magnetic resonance imaging (MRI) is a noninvasive technique
      used to accurately and reproducibly measure biological parameters such as left
      ventricular mass. However, some subjects either refuse or are unable to complete
      testing, and the impact of excluding these missing data from predictive models is
      unknown. METHODS: Multiple imputation was applied to cardiac MRI data that were
      previously analyzed using a complete case approach. The model variables - 10
      traditional cardiovascular risk factors and five sociodemographic variables -
      were used as a basis for imputation. Men and women were imputed separately. The
      primary focus was assessing the change in the cardiovascular predictors of left
      ventricular geometry and systolic function. RESULTS: Although 27% of participants
      were missing cardiac MRI data, multiple imputation returned results similar to
      those of a complete case analysis. These results were robust to the point of
      including additional variables in the imputation analysis above and beyond the
      model variables. The degree of variance explained by the models increased
      marginally but the statistical inference was altered for only two predictors out
      of 53 cardiovascular risk factors using multiple imputation. DISCUSSION: The
      results suggest that the cardiac MRI data in the Multi-Ethnic Study of
      Atherosclerosis (MESA) do not substantively change when missing data are handled
      using multiple imputation. Future analyses of cardiac MRI data may consider the
      complete case approach to be adequate despite the high rate of missing data in
      this population.

PMID- 19584979
TI  - Effect of angiotensin-converting enzyme inhibition on C-reactive protein levels:
      the ramipril C-reactive pRotein randomized evaluation (4R) trial results.
AB  - BACKGROUND: Plasma levels of the inflammatory biomarker C-reactive protein (CRP)
      predict cardiovascular risk and may represent a target for treating and/or
      monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme
      inhibitors on CRP levels has not been adequately studied. METHODS: A total of 264
      men and women, with CRP levels of 2 mg/L or greater and no history of
      cardiovascular disease, were enrolled in a 12-week randomized, double-blind,
      placebo-controlled study. Participants were randomly assigned to receive 10
      mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome
      measure was the change in CRP levels from baseline to 12 weeks in the ramipril-
      versus placebo treated patients. RESULTS: The mean (+/- SD) age was 53+/-9 years
      (60% men). Baseline demographics were similar between the volunteers allocated to
      receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84
      mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP
      values over 12 weeks was --13.2% (95% CI --22.3% to --3.2% ) in the placebo group
      compared with --21.1% (95% CI --29.9% to --11.2%) in the ramipril group (P
      nonsignificant), indicating no significant reduction in the primary end point of
      the trial. CONCLUSIONS: A 12-week ramipril treatment protocol for healthy middle
      aged volunteers did not lower CRP levels compared with placebo. However, because
      of the inherent variability of CRP levels, a much larger study is required to
      exclude a small treatment effect.

PMID- 19584980
TI  - Effects of therapy using the Celacade system on structural and functional cardiac
      remodelling in rats following myocardial infarction.
AB  - BACKGROUND: Immune modulation by the Celacade system (Vasogen Inc, Canada)
      decreases mortality and hospitalization in human heart failure. OBJECTIVES: To
      study the effects of Celacade in rats on acute cytokine expression after coronary
      artery ligation, cardiac dimensions following myocardial infarction (MI), and
      systolic and diastolic function of cardiac muscle in MI. METHODS: Celacade
      treatment was administered 14 days before coronary artery ligation and monthly
      after the surgery. Cytokine expression in cardiac tissue was measured on days 1
      and 7 by ELISA in sham rats and in rats with MI (with or without Celacade
      treatment). Echocardiograms were obtained serially for 16 weeks. Force and
      sarcomere length (SL) were measured by strain gauge and laser diffraction in
      isolated right ventricle trabeculas at 16 weeks. The inotropic effect of pacing
      on force was quantified as F5 Hz/0.5 Hz. Diastolic dysfunction was quantified as
      the root mean square of spontaneous SL fluctuations. RESULTS: Celacade inhibited
      transforming growth factor beta-1 production in the infarct area on day 7
      (191.6+/-22.6 pg/mg versus 275.4+/-30.1 pg/mg; P<0.05), but did not attenuate
      cardiac dilation in MI. Celacade restored positive inotropism of pacing in MI (F5
      Hz/0.5 Hz in Celacade, 219.1+/-46.7%; MI, 148.1+/-27.1% [P<0.05 compared with
      211.4+/-37.9% in sham]). Celacade reduced diastolic dysfunction in MI (root mean
      square of spontaneous SL fluctuations: 121+/-15% and 143+/-19% with Celacade
      versus 184+/-19% and 190+/-26% without Celacade at 26 degrees C and 36 degrees C,
      respectively) compared with sham (100%; P<0.05). CONCLUSIONS: Celacade reduces
      the increase of transforming growth factor beta-1 expression during the acute
      stage of MI in rats, but does not prevent chronic cardiac dilation. Celacade
      restores the positive inotropic effect of increased pacing rate in trabeculas
      from rat right ventricles with large MIs and reduces diastolic dysfunction.

PMID- 19584982
TI  - The Saudi Project for Assessment of Coronary Events (SPACE) registry: design and
      results of a phase I pilot study.
AB  - OBJECTIVE: The delay between the availability of clinical evidence and its
      application to the care of patients with acute coronary syndrome (ACS) in the
      Kingdom of Saudi Arabia remains undefined. The Saudi Project for Assessment of
      Coronary Events (SPACE) registry provides a comprehensive view of the current
      diagnostic and treatment strategies for patients with ACS; thus, the registry may
      be used to identify opportunities to improve the care of these patients. METHODS:
      Eight hospitals in different regions of Saudi Arabia were involved in the pilot
      phase of the registry, from December 2005 to July 2006. The study patients
      included individuals with ST segment elevation myocardial infarction (STEMI), non
      STEMI and unstable angina. RESULTS: A total of 435 patients (77% men and 80%
      Saudis) with a mean age of 57.1 years were enrolled. Medical history included
      previously diagnosed ischemic heart disease (32%), percutaneous coronary
      intervention (12%), diabetes mellitus (53%), hypertension (48%), current smoking
      (39%), hyperlipidemia (31%) and family history of premature coronary artery
      disease (11%). The median door-to-needle time for fibrinolytic therapy received
      by patients with STEMIs was 90 min. Inhospital medications included
      acetylsalicylic acid (98%), clopidogrel (73%), angiotensin- converting enzyme
      inhibitors (74%), beta-blockers (73%), statins (88%), unfractionated heparin
      (80%), low-molecular weight heparin (22%) and glycoprotein IIb/IIIa inhibitors
      (9%). The inhospital mortality rate was 5%. CONCLUSION: The first nationwide
      registry of patients with ACS in the Kingdom of Saudi Arabia is presented. In
      contrast to registries from developed countries, our cohort is characterized by a
      younger age at presentation and a much higher prevalence of diabetes mellitus.
      Most patients with STEMIs did not receive fibrinolytic therapy within the time
      recommended in the American College of Cardiology/American Heart Association
      guidelines. The results of the present pilot study show potential targets for
      improvement in care.

PMID- 19584983
TI  - Hypertrophic obstructive cardiomyopathy complicated by ruptured chordae tendinea
      to the posterior mitral leaflet and severe congestive heart failure.
AB  - A 63-year-old woman with hypertrophic obstructive cardiomyopathy developed
      rapidly progressive fatigue, shortness of breath and congestive heart failure. A
      transesophageal echocardiogram demonstrated ruptured chordae to the posterior
      mitral valve leaflet with severe mitral regurgitation. Mitral valve replacement
      eliminated the outflow gradient. Acute or subacute hemodynamic deterioration in a
      patient with hypertrophic obstructive cardiomyopathy should lead to a search for
      associated lesions.

PMID- 19584981
TI  - Effect of interleukin-15 on the course of myocarditis in Coxsackievirus B3
      infected BALB/c mice.
AB  - OBJECTIVE: Cytokines have an important role in both the initiation and
      perpetuation of viral myocarditis. Because a causative therapy of myocarditis is
      not yet well established and immunomodulation is a promising approach, the
      influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of
      experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined.
      METHODS: Hearts from CVB3-infected (n=14), sham-infected (n=14) and CVB3-infected
      BALB/c mice treated with IL-15 (n=6) or a competitive IL-15 fusion protein (n=6)
      were analyzed for hemodynamic function, cellular infiltrates and myocardial
      collagen content. RESULTS: Induction of myocarditis was associated with
      significant loss of body and heart weight, decreased left ventricular function,
      and increased collagen content and cellular infiltrates in the myocardium.
      Treatment of infected animals with IL-15 resulted in normalization of body and
      heart weight, and significantly improved systolic and diastolic left ventricular
      function, comparable with that of uninfected animals. This was paralleled by a
      significant reduction of myocardial collagen content to levels observed in
      animals without disease and by markedly reduced cellular infiltration of
      lymphocytes and macrophages in the myocardium. Inhibition of intrinsic IL-15 with
      IL-15 fusion protein tended to aggravate the disease. CONCLUSIONS: Treatment with
      IL-15 has a positive effect on CVB3- induced murine myocarditis and seems to be a
      promising approach to modifying clinical course, hemodynamics and histopathology
      of virus-induced myocarditis. Further studies are needed to identify the
      underlying mechanisms.

PMID- 19584984
TI  - Reversible left ventricular dysfunction resembling Takotsubo syndrome after self
      injection of adrenaline.
AB  - Transient left ventricular (LV) ballooning syndrome, or Takotsubo syndrome, is
      characterized by a reversible LV dysfunction. The pathophysiology has not been
      fully elucidated, but an excess of catecholamines seems to have an essential
      role. The case of a 27-year-old man who developed transient LV dysfunction
      resembling Takotsubo syndrome after self-injection of adrenaline is described.
      The present case may provide additional evidence to the hypothesis of excess
      sympathetic activation in LV ballooning syndrome.

PMID- 19584986
TI  - ST segment elevation in precordial leads during percutaneous coronary
      intervention of the right coronary artery.

PMID- 19584985
TI  - Cardiac hazard associated with eating habits. A case of infected intrapericardial
      foreign body due to an ingested toothpick.
AB  - An unusual case of a toothpick perforating the distal one-third of the duodenum,
      penetrating the inferior vena cava and thereafter migrating to the right atrium
      with extensive pericardial fibrosis is reported. A 60-year-old man was admitted
      to the emergency department because of epigastric pain, which had progressively
      worsened. After partial recovery, he was discharged. However, after four episodes
      of different gastrointestinal bacteria septicemias of unknown origin over a
      period of five months, the patient was transferred to Laval Hospital (Laval,
      Quebec) for clinical investigation. Cardiac echocardiography demonstrated a right
      atrial mass, suggestive of the presence of a thrombus. Thus, after exploratory
      thoracotomy was performed to remove the so-called thrombus, a toothpick was found
      in the right atrium.

PMID- 19584987
TI  - Left ventricular apical cystic thrombus mimicking a hydatid cyst.

PMID- 19584988
TI  - Screening for breast cancer should be an integral part of myocardial perfusion
      imaging.

PMID- 19584989
TI  - Pulsus alternans in critical aortic stenosis.

PMID- 19584990
TI  - "But the MRI of the ankle is normal...".

PMID- 19584991
TI  - Effect of simulated lateral process talus "fracture excision" on its ligamentous
      attachments.
AB  - Recent epidemiologic studies highlight lateral talar process fractures as
      snowboarder's fracture or snowboarder's ankle. Snowboarding is the fastest
      growing sport worldwide, so lateral talar process fractures are increasing in
      frequency and mandating a more careful assessment of injury patterns, surrounding
      tissue involvement, and treatment strategy. In this study, we evaluated the
      effects of lateral talar process fracture on the footprints of 3 lateral
      stabilizing ligaments of the ankle and subtalar joint-the lateral talocalcaneal
      ligament (LTCL), the anterior talofibular ligament (ATFL), and the posterior
      talofibular ligament (PTFL). The musculotendinous structures from 10 fresh
      cadaveric limbs were removed and the distal fibula reflected to provide
      visualization of the lateral talar process and ligamentous attachments. Length
      and width of the LTCL, ATFL, and PTFL footprints on the lateral process of the
      talus were measured with calipers before and after removal of a 1-cm(3) simulated
      fracture fragment. Relative changes in the attachment site areas for the 3
      ligaments were determined. Mean pre-excision footprint areas were 80.57 mm(2)
      (LTCL), 224.38 mm(2) (ATFL), and 394.18 mm(2) (PTFL); mean postexcision footprint
      areas were 2.10 mm(2) (LTCL), 194.89 mm(2) (ATFL), and 335.18 mm(2) (PTFL); and
      mean decreases calculated as percentages of the original areas were 97.5% +/-
      3.5% (LTCL), 11.7% +/- 13.0% (ATFL), and 14.3% +/- 12.3% (PTFL). Removal of a 1
      cm(3) bony fragment from the lateral talar process involves 3 of the major
      lateral stabilizing ligaments: approximately 100% of LTCL and approximately 10%
      to 15% of ATFL and PTFL.

PMID- 19584992
TI  - Rate of return of functional outcome after open reduction and internal fixation
      of unstable ankle fractures.
AB  - In the prospective cohort study reported here, we used the Short Musculoskeletal
      Function Assessment (SMFA) questionnaire to assess rate of return of functional
      outcome after open reduction and internal fixation of unstable ankle fractures
      (Orthopaedic Trauma Association/Arbeitsgemeinschaft fur Osteosynthesefragen
      [OTA/AO] 44B and 44C) at a level II trauma center over the course of 1 year. The
      entire group of 69 consecutive adults improved significantly (P<.01) on the SMFA
      Emotional Status and Dysfunction scales from 2 to 4 months and on the Mobility
      and Daily Activities scales from 2 to 4 months and from 4 to 6 months. There were
      no significant changes on the Arm/Hand Function and Bother scales. There was a
      significant effect of age on Mobility, Daily Activities, and Dysfunction, with
      older patients (> or = 50 years) obtaining higher (worse) scores. There was no
      significant effect on patient sex on any of the scales. Patients with 44C
      fractures (vs 44B fractures) had significantly (P = .05) higher mean Bother
      scores at 6 months. There were no significant differences arising from presence
      or absence of a fracture of the medial malleolus. Our SMFA data show that older
      patients (> or = 50 years) and patients with 44C fractures had slower return to
      maximal function and higher Bother scores at 6 months. All groups reached a
      relatively stable functional outcome by 6 months after injury, but their mobility
      did not return to population norms over the same period.

PMID- 19584993
TI  - Sacral stress fractures in children.

PMID- 19584994
TI  - Bilateral fractures of the medial malleoli without a history of trauma.

PMID- 19584995
TI  - Footdrop without significant pain as late presentation of acute peroneal
      compartment syndrome in an intercollegiate football player.

PMID- 19584996
TI  - E-prescribing and the Physician Quality Reporting Initiative: get in while the
      getting is good!

PMID- 19584997
TI  - Open scapula resection in beach-chair position for treatment of snapping scapula.
AB  - We describe a technique of resecting the superomedial border of the scapula for
      treatment of "snapping scapula." We have performed 5 consecutive open resections
      with the patient in the beach-chair position, and results have been good. This
      technique may be of particular benefit in patients who undergo concomitant
      glenohumeral arthroscopy.

PMID- 19584998
TI  - Posterior ankle impingement: os trigonum syndrome.

PMID- 19584999
TI  - Simultaneous solitary glomus tumors in nonadjacent digits.

PMID- 19585000
TI  - A rare case of chondromyxoid fibroma of the scapula.

PMID- 19585001
TI  - Malignant peripheral nerve sheath tumor of the lumbar spine.

PMID- 19585002
TI  - Rare extraskeletal osteosarcoma in the anterolateral right leg of a 37-year-old
      man.

PMID- 19585004
TI  - Stable G-quadruplexes are found outside nucleosome-bound regions.
AB  - Unusual DNA structures such as four-stranded G-quadruplexes have been found to
      form in vivo and to play regulatory roles. However, since DNA is normally present
      as chromatin, with the double helix wrapped around histone proteins, it is
      unclear how a G-quadruplex could form in such a region. Here, we show that
      regulatory G-quadruplexes found upstream of transcription start sites are in fact
      located in a region depleted of nucleosomes, and that in general in both
      Caenorhabditis elegans and humans, stable G-quadruplexes are located outside
      nucleosome-bound regions, hence making it easier for them to form in vivo.

PMID- 19585005
TI  - A dependency graph approach for the analysis of differential gene expression
      profiles.
AB  - A central aim of differential gene expression profile analysis is to provide an
      interpretation of given data at the level of biological processes and pathways.
      However, traversing descriptive data into context is not straightforward. We
      present a gene-centric dependency graph approach supporting an interpretation of
      omics profiles at the level of affected networks. The core of our dependency
      graph comprises data objects encoding the functional categorization of a
      particular gene, its tissue-specific reference gene expression, as well as known
      interactions and subcellular location of assigned proteins. On the basis of these
      genome, transcriptome, and proteome data we compute pair-wise object (gene)
      dependencies and interpret them as weighted edges in a dependency graph. Mapping
      of omics profiles on this graph can be used to identify connectors linking
      features of the omics list, in turn providing the basis for identification of
      subgraphs and motifs characterizing the cellular state under analysis. We
      exemplify this approach by analyzing differential gene expression data
      characterizing B-cell lymphoma and demonstrate the identification of B-cell
      lymphoma associated subgraphs.

PMID- 19585003
TI  - Towards inferring time dimensionality in protein-protein interaction networks by
      integrating structures: the p53 example.
AB  - Inspection of protein-protein interaction maps illustrates that a hub protein can
      interact with a very large number of proteins, reaching tens and even hundreds.
      Since a single protein cannot interact with such a large number of partners at
      the same time, this presents a challenge: can we figure out which interactions
      can occur simultaneously and which are mutually excluded? Addressing this
      question adds a fourth dimension into interaction maps: that of time. Including
      the time dimension in structural networks is an immense asset; time
      dimensionality transforms network node-and-edge maps into cellular processes,
      assisting in the comprehension of cellular pathways and their regulation. While
      the time dimensionality can be further enhanced by linking protein complexes to
      time series of mRNA expression data, current robust, network experimental data
      are lacking. Here we outline how, using structural data, efficient structural
      comparison algorithms and appropriate datasets and filters can assist in getting
      an insight into time dimensionality in interaction networks; in predicting which
      interactions can and cannot co-exist; and in obtaining concrete predictions
      consistent with experiment. As an example, we present p53-linked processes.

PMID- 19585006
TI  - Analysis of structured and intrinsically disordered regions of transmembrane
      proteins.
AB  - Integral membrane proteins display two major types of transmembrane structure,
      helical bundles and beta barrels. The main functional roles of transmembrane
      proteins are the transport of small molecules and cell signaling, and sometimes
      these two roles are coupled. For cytosolic, water-soluble proteins, signaling and
      regulatory functions are often carried out by intrinsically disordered regions.
      Our long range goal is to determine whether integral membrane proteins likewise
      use disordered regions for signaling and regulation. Here we carried out a
      systematic bioinformatics investigation of intrinsically disordered regions
      obtained from integral membrane proteins for which crystal structures have been
      determined, and for which the intrinsic disorder was identified as missing
      electron density. We found 120 disorder-containing integral membrane proteins
      having a total of 33675 residues, with 3209 of the residues distributed among 240
      different disordered regions. These disordered regions were compared with those
      obtained from water-soluble proteins with regards to their amino acid
      compositional biases, and to the accuracies of various disorder predictors. The
      results of these analyses show that the disordered regions from helical bundle
      integral membrane proteins, those from beta barrel integral membrane proteins,
      and those from water soluble proteins all exhibit statistically distinct amino
      acid compositional biases. Despite these differences in composition, current
      algorithms make reasonably accurate predictions of disorder for these membrane
      proteins. Although the small size of the current data sets are limiting, these
      results suggest that developing new predictors that make use of data from
      disordered regions in helical bundles and beta barrels, especially as these
      datasets increase in size, will likely lead to significantly more accurate
      disorder predictions for these two classes of integral membrane proteins.

PMID- 19585011
TI  - Copper-catalyzed cyclization reactions for the synthesis of alkaloids.
AB  - Copper-mediated Ullmann type transformations have recently evolved as useful and
      valuable synthetic tools in organic synthesis. If newly developed catalytic
      systems are readily available, inexpensive, and tolerate most functional groups,
      they also provide new opportunities in natural product synthesis since they allow
      new and efficient retrosynthetic disconnections. They are also especially
      convenient for the development of straightforward cyclization and
      macrocyclization procedures. The present article showcases some examples of
      copper-catalyzed cyclization reactions for the synthesis of alkaloids we have
      recently developed.

PMID- 19585012
TI  - Structural analysis of the Gly-rich region in spider dragline silk using stable
      isotope labeled sequential model peptides and solid-state NMR.
AB  - The local structure of the Gly rich region in synthetic model peptides of spider
      dragline silk was analyzed with solid-state NMR and no dominant secondary
      structure was revealed.

PMID- 19585010
TI  - Total synthesis and study of myrmicarin alkaloids.
AB  - The myrmicarins are a family of air- and temperature-sensitive alkaloids that
      possess unique structural features. Our concise enantioselective synthesis of the
      tricyclic myrmicarins enabled evaluation of a potentially biomimetic assembly of
      the complex members via direct dimerization of simpler structures. These studies
      revealed that myrmicarin 215B undergoes efficient and highly diastereoselective
      Bronsted acid-induced dimerization to generate a new heptacyclic structure,
      isomyrmicarin 430A. Mechanistic analysis demonstrated that heterodimerization
      between myrmicarin 215B and a conformationally restricted azafulvenium ion
      precursor afforded a functionalized isomyrmicarin 430A structure in a manner that
      was consistent with a highly efficient, non-concerted ionic process. Recent
      advancement in heterodimerization between tricyclic derivatives has enabled the
      preparation of strategically functionalized hexacyclic structures. The design and
      synthesis of structurally versatile dimeric compounds has greatly facilitated
      manipulation of these structures en route to more complex myrmicarin derivatives.

PMID- 19585013
TI  - Enhanced fluorescence sensing of hydroxylated organotins by a boronic acid-linked
      Schiff base.
AB  - A simple Schiff base, 2-(2',4'-dihydroxybenzylidene)aminobenzeneboronic acid, was
      found to show a fluorescence enhancement in the presence of hydroxylated
      organotins in aqueous solution.

PMID- 19585014
TI  - Design and construction of a box-shaped 3D-DNA origami.
AB  - A box-shaped 3D-DNA origami has been successfully constructed by selective
      closing of a preformed open motif, and identified by atomic force microscopy and
      dynamic light scattering analysis.

PMID- 19585015
TI  - Hydrogen generation: catalytic acceleration and control by light.
AB  - The ruthenium-catalyzed generation of hydrogen from formic acid is significantly
      accelerated by light.

PMID- 19585017
TI  - Water co-encapsulation in an inverted molecular capsule.
AB  - Comparison of water-free and water-mediated recognition processes within a
      synthetic resorcinarene-based self-assembled capsule shows that water can change
      the stoichiometry of binding as well as the selectivity and it can substantially
      restrict guest dynamics within the binding site.

PMID- 19585016
TI  - Upconverting luminescent nanomaterials: application to in vivo bioimaging.
AB  - In this report, the development of multi-channel anti-Stokes luminescent Y2O3
      nanoparticles for application to in vivo upconversion imaging is detailed.

PMID- 19585019
TI  - Substituent-dependent exchange mechanisms in highly fluxional RSn9(3-) anions.
AB  - 119Sn NMR studies show that the RSn9(3-) ions (R=i-Pr, Sn(C6H11)3) are highly
      fluxional in solution, where the exchange mechanisms involve rapid migration of
      the R group in the latter but not in the former.

PMID- 19585018
TI  - Hydrogen-bonded multilayer of pH-responsive polymeric micelles with tannic acid
      for surface drug delivery.
AB  - We report the design of a platform for the delivery of hydrophobic drugs
      conjugated to block copolymer micelles via pH-responsive linkage that are
      assembled within hydrogen-bonded polymer multilayer thin films.

PMID- 19585020
TI  - Bio-inspired chemical reactors for growing aligned gold nanoparticle-like wires.
AB  - Bioinspired masks, created by merging sol-gel chemistry with biotemplating, were
      used as local chemical reactors to grow aligned arrays of gold nanoparticle-like
      wires.

PMID- 19585021
TI  - Carbon-titania composite substrates for fuel cell catalyst applications.
AB  - We report a sol-gel route to synthesize optimized carbon-titania composite
      substrates, which have more than twice the surface area, nearly three times
      higher corrosion resistance and improved hydrogen adsorption-desorption area
      retention compared to the commercial Vulcan XC-72 carbon substrates.

PMID- 19585022
TI  - Interplay of metal-allyl and metal-metal bonding in dimolybdenum allyl complexes.
AB  - Addition of PMe3 to Mo2(allyl)4 afforded Mo2(allyl)4(PMe3)2, in which two of the
      allyl groups adopt an unprecedented micro2-eta1,eta3 bonding mode; theoretical
      studies elucidate the roles of the sigma- and pi-donor ligands in the interplay
      of metal-allyl and metal-metal bonding.

PMID- 19585023
TI  - Water-soluble nanorods self-assembled via pristine C60 and porphyrin moieties.
AB  - A novel water-soluble nanorod is discussed, which is prepared via the self
      assembly of pristine C60 and a double-sided porphyrin projecting four beta
      cyclodextrins from each face.

PMID- 19585024
TI  - Organic nanotubes assembled from isophthalamides and their application as
      templates to fabricate Pt nanotubes.
AB  - A new class of organic nanotubes have been assembled from simple isophthalamide
      derivatives and their surface can be conveniently coated with Pt, which form new
      Pt nanotubes after the inside organic materials are removed with hot methanol.

PMID- 19585025
TI  - Exciplex quenching of a luminescent cyclometallated platinum complex by extremely
      poor Lewis bases.
AB  - An intensely phosphorescent Pt complex in cyclohexane is efficiently quenched by
      exciplex formation with extremely weak Lewis bases such as toluene and other
      aromatic compounds.

PMID- 19585026
TI  - Sulfur-tagged metal-organic frameworks and their post-synthetic oxidation.
AB  - A series of sulfur-tagged zinc MOFs containing functionalised 4,4'
      biphenyldicarboxylate ligands has been prepared: oxidative post-synthetic
      modification with dimethyldioxirane has converted the sulfide tags into sulfones,
      leaving the MOF networks intact.

PMID- 19585027
TI  - Alloyed semiconductor nanocrystals with broad tunable band gaps.
AB  - Nearly monodisperse alloyed (CuInS2)x(ZnS)1-x nanocrystals with cubic and
      hexagonal phases were successfully synthesized for the first time, and the band
      gaps of these alloyed nanocrystals can be tuned in the broad range of 1.5 to 3.7
      eV by changing the ratio of CuInS2 to ZnS.

PMID- 19585028
TI  - Glycine and L-serine crystalline perhydrates.
AB  - We report the first crystalline amino acid perhydrates, show induced chirality of
      hydrogen peroxide in L-serine perhydrate, and demonstrate that the glycine
      perhydrate contains 40.47 wt% hydrogen peroxide.

PMID- 19585029
TI  - Sandwich nanohybrid of single-walled carbon nanohorns-TiO2-porphyrin for
      electrocatalysis and amperometric biosensing towards chloramphenicol.
AB  - A sandwich nanohybrid of single-walled carbon nanohorn-TiO2-porphyrin was
      prepared via the dentate binding of TiO2 nanoparticles to carboxylate groups,
      which showed an excellent electrocatalytic activity towards the reduction of
      chloramphenicol in neutral media, leading to a highly sensitive and stable
      amperometric biosensor for chloramphenicol.

PMID- 19585030
TI  - Mismatch DNA-specific enzymatic cleavage employed in a new method for the
      electrochemical detection of genetic mutations.
AB  - Utilizing enzymatic mismatched DNA-specific cleavage and electrocatalytic
      signaling, a new electrochemical method for the detection of DNA mutations was
      developed and successfully applied to detect various mutations in the BRCA1 gene.

PMID- 19585032
TI  - Self-assembly of bent-core liquid crystals: formation of a modulated smectic
      phase with p2gg lattice to escape anticlinic tilt.
AB  - A new silyl terminated bent-core mesogen was synthesized which shows a randomly
      tilted SmCR phase and a columnar phase with p2gg lattice as new modes of self
      assembly in this class of compounds.

PMID- 19585031
TI  - Probing a sialyltransferase's recognition domain to prepare alpha(2,8)-linked
      oligosialosides and analogs.
AB  - We report the first observation that a monosialyl residue is the essential
      structural element recognized by the enzyme CST-II; this has resulted in an
      attractive route to synthesize a series of alpha(2,8)-linked oligosialic acids
      and their thioanalogs in one step.

PMID- 19585033
TI  - Surface texturing of porous silicon with capillary stress and its
      superhydrophobicity.
AB  - Lotus-leaf-like superhydrophobic surfaces have been prepared simply by surface
      texturing of porous silicon films with capillary stress and the mechanism was
      studied in detail.

PMID- 19585034
TI  - Jahn-Teller distortions of six-coordinate CuII compounds: cis or trans?
AB  - Unlike their octahedral analogues, copper(II) compounds with trigonal prismatic
      stereochemistry undergo an elongation of two bonds in cis positions due to a Jahn
      Teller effect, a behavior that can also occur in slightly twisted octahedra.

PMID- 19585035
TI  - Engineering noncovalent spin-spin interactions in an organic-pillared spin cage.
AB  - A prism-shaped spin cage, in which two radical panels were aligned in a face-to
      face fashion at a distance of 6.8 A, efficiently induced through-space metal
      radical spin-spin interaction by encapsulation of a planar copper complex.

PMID- 19585036
TI  - Molecular recognition at the liquid-liquid interface of colloidal microcapsules.
AB  - Dithiocarbamate chemistry is used as a crosslinking tool to fabricate FePt
      colloidal microcapsules which provide a versatile scaffold for "host-guest"
      recognition at the liquid-liquid interface.

PMID- 19585037
TI  - Highly enantioselective organocatalytic Michael addition of nitroalkanes to 4-oxo
      enoates.
AB  - A useful Michael addition reaction using nitroalkanes as the nucleophile and 4
      oxo-enoates as the Michael acceptor has been disclosed, and the reaction allows
      expedient access to functionalized chiral gamma-keto esters in high yields and
      excellent enantioselectivities (up to 98% ee), with a low catalyst loading.

PMID- 19585038
TI  - Prenucleation and coalescence of cobalt nanoclusters mediated by multivalent
      calixarene complexes.
AB  - The formation of cobalt nanoclusters from polynuclear Co-alkyne species can be
      directed by multivalent calixarene ligands; thermochemical studies of Con
      calixarenes reveal the influence of multivalency in prenucleation and postnuclear
      growth processes.

PMID- 19585039
TI  - The molecular form of mercury in biota: identification of novel mercury peptide
      complexes in plants.
AB  - The molecular structure of a variety of novel mercury-phytochelatin complexes was
      evidenced in rice plants exposed to inorganic mercury (Hg2+) using RP-HPLC with
      simultaneous detection via ICP-MS and ES-MS.

PMID- 19585040
TI  - Phosphate-assisted peptide ligation.
AB  - A novel ligation method for the synthesis of phosphopeptides and peptides is
      described, which utilises the inherent reactivity of a peptide bearing an N
      terminal phosphoserine or phosphothreonine residue to facilitate amide bond
      formation with a range of C-terminal peptide thioesters.

PMID- 19585041
TI  - Efficient synthesis of 2,3-dihydro-1H-pyrazoles via a highly selective Pd(0)
      catalyzed coupling-cyclization reaction of terminal 2-substituted 2,3-allenyl
      hydrazines with aryl iodides.
AB  - 2,3-dihydro-1H-pyrazoles were highly selectively synthesized via the Pd(0)
      catalyzed coupling-cyclization reaction of 4-non-substituted 2-substituted 2,3
      allenyl hydrazines with aryl iodides in moderate to good yields.

PMID- 19585043
TI  - A heterocyclic organogallium peroxide with two dialkylgallium groups bridged by a
      peroxide dianion.
AB  - Treatment of Li[H2GaR2] [R=CH(SiMe3)2] with the hydrogen peroxide adduct
      (H2O2)2.DABCO (DABCO=diazabicyclooctane) afforded a heterocyclic digallium
      peroxide, [R2Ga(micro,eta1,eta1-O2)(micro-OH)GaR2]Li(DABCO) (2), in which two
      dialkylgallium groups are bridged by an oxidizing peroxo and a hydroxo ligand.

PMID- 19585042
TI  - Highly asymmetric cobalt-catalyzed aziridination of alkenes with
      trichloroethoxysulfonyl azide (TcesN3).
AB  - A Co(II)-based catalytic system has been developed for asymmetric aziridination
      of alkenes with trichloroethoxysulfonyl azide (TcesN3) under mild conditions,
      forming the corresponding N-Tces-aziridines in high yields and excellent
      enantioselectivities.

PMID- 19585044
TI  - A macrocyclic coumarin-containing tripeptide via CuAAC chemistry.
AB  - A Cu-catalysed macrocyclisation was performed to obtain a macrocyclic coumarin
      containing tripeptide for use in thrombin activity measurements.

PMID- 19585045
TI  - Synthetic studies on vincorine: access to the 3a,8a-dialkyl-1,2,3,3a,8,8a
      hexahydropyrrolo[2,3-b]indole skeleton.
AB  - Synthetic studies on vincorine are described; the conversion of 3-aminoethyl-3
      alkyloxindoles to 3a,8a-dialkyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles has
      been achieved through an addition-cyclization sequence, and a fully
      functionalized key intermediate was constructed with this method.

PMID- 19585046
TI  - Luminescent, water-soluble gold nanoparticles functionalised with 3MLCT emitting
      rhenium complexes.
AB  - Rhenium complexes functionalised with thioester-terminated alkyl chains can be
      attached to gold nanoparticles to yield water-soluble, visibly luminescent Re-GNP
      hybrid conjugates.

PMID- 19585047
TI  - Fluorescent alpha-cyclodextrin as a chemosensor for halomethanes.
AB  - A new fluorescent chemosensor, NBDamine-appended alpha-cyclodextrin, was prepared
      and showed high selectivity for perhalogenated methanes via multisite
      interactions between the perhalogenated methane and the cyclodextrin molecule.

PMID- 19585048
TI  - Nickel-catalyzed [2+2+2] cycloaddition of arynes and an unactivated alkene:
      synthesis of 9,10-dihydrophenanthrene derivatives.
AB  - A nickel-catalyzed [2+2+2] cycloaddition of two molecules of aryne and an alkene
      moiety in a alpha,omega-diene afforded 9,10-dihydrophenanthrene derivatives in
      good yields.

PMID- 19585049
TI  - Synthesis of highly stable pure-silica thin-walled hexagonally ordered mesoporous
      material.
AB  - Hexagonally ordered mesoporous silica with a very narrow mesopore size
      distribution and exceptionally high stability paired with unusually thin pore
      walls was prepared using piperidine and cetyltrimethylammonium bromide.

PMID- 19585050
TI  - Superconducting TaS2-xIy hierarchical nanostructures.
AB  - Iodine-doped TaS2 hierarchical nanostructures, for which nanorod arrays are
      vertically grown on the edge of nanosheets, were prepared and showed
      superconductivity below 5 K.

PMID- 19585051
TI  - Regioselective formation of interlocked dicarba bridges in naturally occurring
      cyclic peptide toxins using olefin metathesis.
AB  - Bis-dicarba analogues of native dicystine-containing alpha-conotoxin Rg1A, an
      analgesic peptide isolated from cone snail venom, were constructed on resin using
      a regioselective metathesis-hydrogenation strategy.

PMID- 19585052
TI  - Highly active new chiral Co(III) salen catalysts immobilized by electrostatic
      interaction with sulfonic acid linkages on ordered mesoporous SBA-16 silica.
AB  - New chiral cobalt(III) salen complexes immobilized via HO3S-linkers on ordered
      SBA-16 by electrostatic interactions showed very high activity in
      enantioselective ring-opening reactions of racemic epoxides.

PMID- 19585053
TI  - Encapsulated binding sites--synthetically simple receptors for the binding and
      transport of HCl.
AB  - We report a receptor with an encapsulated amine/amide binding site, which binds
      HCl with high affinity in organic media--the rate of HCl transport through an
      apolar phase is controlled by the degree of encapsulation of the HCl binding
      site.

PMID- 19585056
TI  - Dietary supplement use by adolescents.
AB  - OBJECTIVES: To review the use, benefits and adverse effects of the main dietary
      supplements consumed by adolescents. SOURCES: The literature review was performed
      using MEDLINE and LILACS databases (1997-2008). We analyzed 377 articles, and 52
      of them were selected as references. SUMMARY OF THE FINDINGS: Consumption of
      dietary supplements is widely spread among adolescents. This habit has often been
      detected in pediatric and adolescent medicine clinics. Most of the time, the use
      of supplements is motivated by the search of the ideal body. Other reasons for
      this practice are: attempt to compensate for an inadequate diet, increase
      immunity, prevent diseases, improve athletic performance and overcome their own
      athletic limits. The dietary supplements most frequently used and for which there
      is little evidence of beneficial effects in healthy adolescents are: proteins,
      amino acids, beta-hydroxy-beta-methylbutyrate, microelements, carnitine,
      creatine, vitamins, caffeine, and bicarbonate. This dietary supplementation may
      be beneficial for competitive athletes who do not have a balanced diet after a
      specific dietary deficiency has been detected. CONCLUSION: The unrestrained
      consumption of dietary supplements should be avoided, since, besides the lack of
      evidence that such practice will lead to improvement of performance, it exposes
      adolescents to several adverse effects. Balanced nutrition, with intake of
      essential energy and nutrients is usually enough to achieve good athletic
      performance. The use of dietary supplements must be allowed only for selected
      cases in which specific nutritional deficiencies are identified.

PMID- 19585057
TI  - New and existing therapeutic options for hand eczema.
AB  - Hand eczema affects up to 10% of the population and encompasses a diverse range
      of morphological presentations and underlying pathophysiological processes. This
      article will review the new and existing treatments that are available for this
      common dermatologic problem.

PMID- 19585058
TI  - Treatments for pityriasis rosea.
AB  - Pityriasis rosea is a common skin disorder in children and young adults. It is a
      self-limiting disease with symptoms that are typically mild and tolerable.
      Consequently, the best treatment remains the one followed so far by generations
      of dermatologists: reassuring the patient and letting the condition go away on
      its own. However, there are times when treatment is recommended. In this paper,
      we review the available treatments for this skin disease.

PMID- 19585059
TI  - Treatments for scalp psoriasis with emphasis on calcipotriol plus betamethasone
      dipropionate gel (Xamiol).
AB  - Scalp psoriasis occurs in 50%-75% of patients with plaque psoriasis. It may be
      the only area of the body affected, or it may be associated with disease
      elsewhere, including psoriatic arthritis. Most cases are treated topically,
      usually with steroids and/or calcipotriol. In 2008, Health Canada and the US FDA
      approved a stable, once-daily 2-compound gel containing calcipotriol and
      betamethasone dipropionate (Xamiol, LEO Pharma; Taclonex Scalp, Warner Chilcott).
      This once-daily therapy improves patient quality of life with a quick onset of
      action and greater efficacy than monotherapy with either ingredient or twice
      daily treatment with calcipotriol 0.005% (Dovonex, LEO Pharma) scalp solution.
      The gel vehicle was developed for ease of use, improved cosmetic acceptability
      and absorption on the scalp. By 2 weeks, approximately 60%, and by 8 weeks,
      approximately 70% of patients have controlled disease (i.e., absent or very mild
      disease). At 8 weeks, the calcipotriol and betamethasone dipropionate gel
      formulation has a safety profile comparable with betamethasone dipropionate and
      is associated with significantly fewer adverse events than calcipotriol. Xamiol
      may be safely used for up to 52 weeks. No cases of atrophy, striae, or steroid
      purpura were noted in two 52-week studies.

PMID- 19585060
TI  - Use of tacrolimus ointment in vitiligo alone or in combination therapy.
AB  - Current treatments for vitiligo are largely unsatisfactory. Topical
      corticosteroids and phototherapy (narrow-band UVB and psoralen+UVA) are the most
      prescribed, however, these therapies are often not effective and have important
      side-effect, especially when used for a long time. Many studies have reported the
      efficacy and safety of tacrolimus ointment in adults and children with vitiligo,
      particularly when located on the head and neck. Successful treatment is possible
      when it is combined with other therapies, such as narrow-band UVB,
      microphototherapy, helium-neon laser, or narrow-band excimer laser.

PMID- 19585062
TI  - Polybrominated diphenyl ethers in the soil of typical industrial city.
AB  - Linfen is generally recognized as one of the most polluted industrial cities in
      China. Indeed, Linfen is affected by heavy polluting industries and faces
      pollution by polybrominated diphenyl ethers (PBDEs). For this study, ten surface
      soil samples covering all of Linfen were collected and analyzed for 42 BDE
      congeners. The total PBDEs concentration ranged from 0.064 to 136.1 ng g-1.
      Moreover, source analysis indicated that PBDEs may be associated with the
      prevalent use of Deca-BDE in the industrial area of the city. Furthermore, higher
      levels of PBDE contamination were observed in south Linfen due to the
      distribution of industrial plants.

PMID- 19585061
TI  - Outcome and length of stay in psychiatric hospitalization, the experience of the
      University Clinic of Turin.
AB  - BACKGROUND: Given the current tendency to shorten psychiatric hospitalization and
      change its organization, an issue could be raised regarding its outcomes.
      PURPOSE: To analyze features related to length of stay in a short-term inpatient
      treatment, to study outcomes and to evaluate the diagnosis-specific effects of
      hospitalization. METHOD: A sample of 310 consecutive hospitalized patients, with
      psychotic disorder, depressive disorder and bipolar disorder (DSM IV-TR), was
      recruited at the University Psychiatric Clinic, Service for Cognitive Disorders,
      Department of Neuroscience, University of Turin. Severity of illness was rated
      using the brief psychiatry rating scale (BPRS). We evaluated relations between
      length of stay and clinical and socio-demographic features (linear regression)
      and possible differences confronting BPRS scores at admission and discharge in
      the different diagnostic subgroups (ANOVA for repeated measures). RESULTS: All
      the sample of patients showed a significant improvement in symptomatology during
      hospitalization. Worse symptomatology in anxiety-depression domain of BPRS at
      admission in the whole sample was positively correlated with length of stay. A
      longer length of stay was also shown in patients with diagnosis of depressive
      disorder. Finally, a different pattern of improvement of BPRS (total score and
      domains) was shown between the different diagnostic groups. CONCLUSION: Brief
      hospitalization in our service was shown to be highly effective. Different
      diagnostic groups had different response to hospitalization, showing faster
      improvement in characteristic symptomatology, but the anxiety-depression domain
      showed the highest percentage of change for all the diagnostic groups. We
      therefore suppose that hospitalization has two effects: a specific (due to
      tailored therapies) and a non-specific one (due to non-specific therapy and to a
      placebo-like effect).

PMID- 19585063
TI  - Effect of cadmium on haemocyte viability of the woodlouse Porcellio laevis
      (Isopoda, Crustacea).
AB  - This study investigated the effects of cadmium on haemocyte viability of the
      woodlouse Porcellio laevis, using the trypan blue exclusion assay. The ultimate
      aim is to determine the usefulness of this cellular response as biomarker of
      cadmium exposure. Results showed that exposure to sublethal concentrations of
      cadmium, with concomitant cadmium accumulation in the body, significantly lowered
      the percentages of viable haemocytes in P. laevis. This response was already
      observed after the first week of exposure and could therefore possibly serve as
      an early warning of cadmium exposure. A field study is needed to validate these
      findings.

PMID- 19585064
TI  - Behavior of simetryn and thiobencarb in the plough zone of rice fields.
AB  - The behavior of simetryn and thiobencarb in flooded rice soil was investigated in
      a 2-year study. The concentrations of simetryn and thiobencarb were in the
      hundreds of MUg kg-1 in the top soil layer (0-5 cm) and became significantly
      lower in tens of MUg kg-1 in the deeper soil layers (5-10 and 10-15 cm). The half
      lives of the two herbicides were also shorter (36 and 17 days for simetryn and
      thiobencarb, respectively) in the top soil layer, as they were most affected by
      environmental conditions, compared with corresponding values of 82 and 69 days in
      the 5-10 cm soil layer. Simetryn concentration was stable, while thiobencarb's
      half-life was 165 days in the 10-15 cm layer. About 35% of the applied mass of
      simetryn and thiobencarb were found in the rice soil compartment.

PMID- 19585065
TI  - A hybrid technique: video-assisted thoracoscopic surgery (VATS) pulmonary
      resections for community-based surgeons.
AB  - BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) for pulmonary
      resection was first described more than 15 years ago, it has yet to gain grass
      roots acceptance. The majority of surgeons who routinely perform VATS resections
      work in academic or government institutions. The perceived complexity of the
      technique, inadequate instrumentation and resources, and concern regarding the
      potential compromise of surgical and oncologic principles may present a greater
      barrier to adoption by community-based surgeons. This article illustrates some of
      the technical aspects of a hybrid technique that enables a single surgeon to
      perform VATS pulmonary resection on a routine basis in a community-based
      practice. METHODS: From January 2005 to March 2008, 492 VATS pulmonary resections
      were performed by a community-based, solo-practice surgeon using a hybrid VATS
      technique. The highlight of this technique is utilization of a thoracoscopy port
      and a utility incision. The advantages of this dual access are ease in
      instrumentation, visualization, lighting, and retraction. In addition, this
      technique allows immediate access under direct vision for urgent control of
      bleeding, which can be difficult using a conventional thoracoscopic approach.
      RESULTS: Mean operative time was 52 (median, 48) minutes. Mean length of stay was
      7 (median, 4) days. Mean length of ICU stay was 1.7 days, with 85% of patients
      having no days spent in the ICU. Mean length of chest tube duration was 4 days.
      Perioperative mortality was 3.5% and overall mortality was 9.8%, with a mean
      follow-up of 239 days. These results compare favorably with the conventional VATS
      approach. CONCLUSIONS: This series shows that our hybrid VATS approach to
      pulmonary resection is safe and feasible at community hospital-based practices.

PMID- 19585066
TI  - Clinical outcomes of endoscopic submucosal dissection for undifferentiated early
      gastric cancer.
AB  - BACKGROUND: Early gastric cancer (EGC) with undifferentiated histology has not
      been generally accepted as an indication for endoscopic treatment. This study was
      designed to evaluate the outcomes and clinicopathological factors associated with
      the complete resection of undifferentiated EGC using endoscopic submucosal
      dissection (ESD). METHODS: A retrospective analysis of prospectively collected
      data was performed on consecutive patients who underwent ESD. Among the 456 EGCs
      treated using ESD at the Seoul National University Hospital, Seoul, Korea,
      between April 2005 and June 2008, 60 lesions (13.2%) were diagnosed as
      undifferentiated gastric cancer (poorly differentiated adenocarcinoma or signet
      ring cell carcinoma). RESULTS: En bloc resection was performed in all lesions
      without significant complications. The size discrepancy between the pretreatment
      endoscopy and the resected specimen was significantly higher in undifferentiated
      EGCs than differentiated EGCs (p = 0.002). The complete resection rate was
      significantly lower for undifferentiated EGC (55%) cases than differentiated EGC
      cases (84.1%; p < 0.001). Independent risk factors for incomplete resection of
      undifferentiated EGC included tumor size >20 mm, submucosal invasion, and
      presence of ulceration. During a mean observation time of 16 months, no
      recurrence developed in any of the patients with undifferentiated EGCs thought to
      be completely resected by ESD. CONCLUSIONS: ESD might be considered an
      alternative treatment modality in carefully selected cases of undifferentiated
      EGC.

PMID- 19585067
TI  - Resident training in minimally invasive surgery: a survey of Canadian department
      and division chairs.
AB  - BACKGROUND: This study aimed to seek the opinions of academic surgical chairs on
      minimally invasive surgery (MIS) education for general surgery residents and to
      identify perceived gaps and trends in educational strategies. METHODS: A national
      survey on attitudes toward MIS was sent to the chairs of departments of surgery
      and divisions of general surgery across the 16 Canadian academic centers. The
      survey contained 34 questions consisting of Likert scales, single answers, and
      multiple-choice questions. Nonresponders were contacted directly. At the time of
      the survey, two department chair positions were vacant. RESULTS: The response
      rate was 87% (26/30). The majority of the centers used early operating room
      exposure to basic MIS cases (92%) and animal labs (85%). Two-thirds of the
      institutions used early operating room exposure to advanced MIS cases (69%) and
      didactic lectures (65%). Half of the academic centers used MIS video (54%) and
      the laparoscopic virtual reality simulator (54%). The least used method was
      computer software (19%). The surgical division and department chairs believed the
      most effective teaching method was early operating room exposure to basic MIS
      cases (100%), followed by the laparoscopic virtual reality simulator (91%) and
      animal labs (88%). Computer software was considered 42% useful, and the least
      useful method was didactic lectures (16%). In the next 5 years, 62% of academic
      centers plan to add laparoscopic virtual reality simulators to their MIS
      curriculum. CONCLUSION: The chairs' opinion on the most effective MIS teaching
      method for residents is basic MIS cases followed by laparoscopic virtual reality
      simulators. The majority of academic institutions plan to add laparoscopic
      virtual reality simulators to the curriculum in the next 5 years.

PMID- 19585069
TI  - Endoscopic submucosal dissection for rectal carcinoid tumors.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has an advantage over
      endoscopic mucosa resection (EMR) by enabling removal of gastrointestinal
      neoplasms en bloc. The ESD procedure is the treatment of choice for rectal
      carcinoids that have classic histologic architecture with minimal cellular
      pleomorphism and sparse mitoses, but it has not been applied for such tumors.
      METHODS: The ESD procedure was performed for patients with colorectal tumors that
      fulfilled the inclusion criteria specifying tumor with a diameter of 10 mm or
      less, no muscular layer invasion, and no metastases to the lymph nodes or distal
      organs. The ESD procedure was performed for patients with rectal carcinoids but
      no node or distal metastasis. RESULTS: This study enrolled 20 rectal carcinoid
      tumors from 20 consecutive patients. The mean tumor size was 7.6 mm (range, 3-16
      mm). En bloc removal was achieved for all the tumors, and the complete resection
      (en bloc with tumor-free lateral/basal margins) rate was 90% (18/20). The two
      cases in which the margins were not evaluable due to burn effects still are free
      of recurrence and metastasis at this writing. Perforation was seen in one case,
      which was managed nonsurgically. CONCLUSIONS: Precise histolopathogic assessment
      of the specimens resected en bloc by ESD may reduce tumor recurrence and
      metastasis after ESD. As the treatment of choice for small rectal carcinoids, ESD
      is associated with nominal risks of metastatic disease.

PMID- 19585068
TI  - Natural orifice translumenal endoscopic surgery (NOTES) partial nephrectomy in a
      porcine model.
AB  - BACKGROUND: This study aimed to evaluate the feasibility of natural orifice
      translumenal endoscopic surgery (NOTES) transgastric partial nephrectomy without
      hilar clamping in a porcine model. METHODS: A 45-kg male pig was placed in the
      supine position after endotracheal general anesthesia. A therapeutic gastroscope
      was introduced through the esophagus, and a 2-cm gastrotomy was performed using a
      diathermy electrocautery needle at the junction of the fundus and the proximal
      body. After incision of Gerota's fascia, the left kidney's upper pole was excised
      using the thulium laser without hilar dissection or clamping. An endoscopic wire
      loop was used to entrap and extract the specimen into the stomach. The
      gastroscope was subsequently withdrawn with the intact specimen. After hemostasis
      via reinsertion of the endoscope was ensured, metal clips were applied
      endoscopically to close the gastrotomy. RESULTS: The total operative time for the
      NOTES transgastric partial nephrectomy was 240 min. Use of the therapeutic double
      channel gastroscope allowed for scarless NOTES. The available 3.7- and 2.8-mm
      gastroscope ports were used for gastrotomy, excision, removal of the specimen,
      and endoscopic clip application. The procedure was performed in a nonischemic
      fashion with application of the thulium laser, which provided adequate
      hemostasis. No further interventions such as suturing of the renal capsule or use
      of hemostatic agents were required. The final specimen was 3 cm in size, and the
      estimated blood loss was 200 ml. A major drawback of the thulium laser was
      excessive smoke produced by vaporization of the tissue, which was minimized with
      the use of external irrigation. CONCLUSION: The findings show that NOTES
      transgastric partial nephrectomy with thulium laser is feasible. Further studies
      are needed to demonstrate long-term efficacy and provide additional data
      regarding practical applications of this novel approach and technique.

PMID- 19585070
TI  - Routine management of stricture after gastric bypass and predictors of subsequent
      weight loss.
AB  - BACKGROUND: Gastrojejunal anastomotic stricture is the most commonly occurring
      short-term complication after Roux-en-Y gastric bypass. Endoscopic balloon
      dilation is the first-line treatment for stricture. However, an optimal dilation
      protocol has not been identified. This study aimed to document routine management
      of stricture after laparoscopic gastric bypass and its impact on postoperative
      weight loss. METHODS: Charts of patients who underwent gastric bypass from 2000
      to 2006 were reviewed using a standardized abstraction form. Patients with
      stricture were matched with control subjects based on age +/-5 years, gender, and
      preoperative body mass index (BMI +/- 5). Patients with at least 6 months of
      follow-up assessment were included in the study. RESULTS: Of the 113 patients
      included in the study, 20% were male, 26% black, 19% Hispanic, and 51% white.
      Their mean age was 42 +/- 10 years (range, 22-66 years). The mean preoperative
      BMI was 47.0 +/- 5.4 kg/m(2) for the case group and 46.6 +/- 5.5 kg/m(2) for the
      control group (p = 0.3). After adjustment for patient characteristics, using a
      larger balloon was associated with reduced odds of stricture recurrence (odds
      ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.85; p = 0.02). All the
      patients were without signs or symptoms of stricture at the last follow-up visit
      (20 +/- 17 months). Weight loss was similar between the two groups. The
      percentage of estimated weight loss (%EWL) at 12 months postoperatively was 66%
      for the study participants and 67% for the control subjects (p = 0.5). Baseline
      alcohol use and higher preoperative BMI were associated with a higher BMI 6
      months postoperatively (p = 0.004 and p < 0.001, respectively). CONCLUSIONS:
      Initial dilation with a larger balloon is safe and may prevent stricture
      recurrence. Further study of modifiable risk factors for reduced weight loss
      after surgery, such as alcohol use, may improve patient outcomes.

PMID- 19585071
TI  - Is laparoscopic fiberoptic choledochoscopy for common bile duct stones a fine
      option or a mandatory step?
AB  - BACKGROUND: Because choledochoscopy often is a challenging maneuver, it would be
      advantageous to define the real utility of its use. This study aimed to compare
      blind exploration of the common bile duct (CBD) with choledochoscopy-assisted CBD
      stone removal in terms of patient outcome and complication rate. METHODS: Two
      groups of patients were prospectively evaluated in a 4-year period. The study
      participants were 36 men and 27 women randomized to group A (n = 32) for a blind
      basket procedure or group B (n = 31) for a choledochoscopy-assisted procedure as
      the first step of laparoscopic CBD stone removal. Patients with preoperatively
      suspected CBD stones (n = 51) and those with unsuspected stones (n = 12) were
      included. The two groups did not differ significantly in terms of anagraphics,
      American Society of Anesthesiology (ASA) score, or previous surgery. All the
      procedures were performed by surgeons skilled in this surgical field.
      Choledochoscopy, when used, was always performed with the instrument connected to
      a camera monitor that had a wide vision, whether in a single-monitor, in a
      picture-in-picture manner, or with the use of an additional monitor. RESULTS:
      From March 2004 to April 2008, 63 patients undergoing CBD exploration for stone
      removal were enrolled in the study. Five of these patients had undergone previous
      endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic sphincterotomy
      (ES). The mean operative time was 107 min for group A and 122 min for group B.
      The mean hospital stay was 3 days for group A and 3.6 days for group B. Clearance
      of CBD stones was achieved laparoscopically in 62 cases. One patient required
      open combined transduodenal papilloplasty and transcholedochotomy. In seven
      cases, blind basket exploration was unable to remove the stones according to the
      cholangiogram, so choledochoscopy was required. Six patients underwent a
      transversal coledocothomy for stone removal. A Kehr T-tube was placed in four of
      these patients. In four group A cases, the papilla was inadvertently passed
      during the procedure. In six group A cases, including the four aforementioned
      cases, a high level of amylases was found on postoperative day 1. At this
      writing, no late complications or stone recurrences have been observed in either
      group. CONCLUSIONS: The laparoscopic basket blind technique and choledochoscopy
      are safe and effective for CBD stone removal. However, the latter seems to be
      better in terms of a higher stone removal rate and fewer minor complications
      despite its longer operation time. In the authors' opinion, it may be preferable
      to reserve ERCP for very high-risk patients, taking into account that in addition
      to the related complications, it results in an approximate 10% rate of recurrent
      or persistent stones.

PMID- 19585073
TI  - Treatment of gallbladder disease during operations Iraqi Freedom and Enduring
      Freedom.
AB  - BACKGROUND: We examined the outcome after treatment for gallbladder disease in
      deployed military service members and the impact of instituting a clinical
      pathway to expedite return to duty (RTD). METHODS: A retrospective chart review
      of 97 medically evacuated patients with gallbladder disease was carried out.
      These patients were evacuated from the field to Landstuhl Regional Medical Center
      (LRMC), Germany, between March 2003 and November 2004. In October 2003, a
      clinical pathway was established to facilitate returning these deployed patients
      back to their combat units. These service members were compared with 90 local
      patients who underwent the same surgery during the study period. RESULTS: Twenty
      nine patients were treated before the implementation of the clinical pathway. Of
      those, five had complications, five were converted to open, and 52% returned to
      their deployed units. After the clinical pathway was established, there were no
      complications (p = 0.023), two were converted to open (p = 0.002), and 84%
      returned to duty (p = 0.002). The Operation Iraqi Freedom (OIF) and Operation
      Enduring Freedom (OEF) service members had delayed presentations for definitive
      treatment. When compared with the local patient group, OIF/OEF surgical cases
      were more often male (78 vs. 32%, p < 0.001), younger (average 31 vs. 35 years, p
      < 0.001), and associated with longer operative times (89 vs. 52 min, p < 0.001),
      and had higher conversion rate to open (7.2 vs. 2.2%, p = 0.17) and higher major
      complication rate (5.1 vs. 0%, p = 0.06). Time to operation and final pathologic
      diagnosis were significantly different between the two groups. CONCLUSIONS:
      Gallbladder surgery can be performed in a delayed manner in the deployed service
      member, although with a significantly higher morbidity as compared with the local
      population. We suggest that changes in the immediate treatment and transportation
      of these service members should occur at the theater level. The use of a clinical
      pathway facilitates the rapid RTD of soldiers diagnosed with gallbladder disease.

PMID- 19585072
TI  - Endoscopic retrograde cholangiography by double balloon enteroscopy in patients
      with Roux-en-Y hepaticojejunostomy.
AB  - BACKGROUND: In patients with Roux-en-Y hepaticojejunostomy (HJ), endoscopic
      retrograde cholangiography (ERC) cannot usually be achieved since the anastomosis
      is not reachable via standard duodenoscope. In this study, we report our
      experience with ERC using double balloon enteroscope (DBE) (DBE-ERC) in patients
      with HJ. METHODS: The DBE-ERC procedures performed since the index case done
      dated May 3, 2006 have been overviewed. RESULTS: Fourteen patients underwent the
      procedure. DBE-ERC was successful in all but one patient, for whom the
      anastomosis could not be reached (success rate to reach anastomosis: 92.9%). The
      remaining 13 patients (7 female, 6 male; age 28-61 years, mean 45.3 years) had 20
      sessions of DBE-ERC. The cannulation of the bile duct was achieved in all
      patients. The procedures, such as sphincteroplasty, dilatation, stone extraction
      and stent placement, were performed. Therapeutic procedures were all successful,
      except for in a single patient, who had the common bile duct filled with multiple
      stones and was referred for surgery. Three patients who had anastomotic stenosis
      treated by stenting are symptom free on follow-up at 3, 9 and 12 months,
      respectively, after stent removal. Retroperitoneal air was detected in a patient
      following stricturoplasty, but recovery was attained with medical treatment
      alone. Mean duration of the procedures was 75 +/- 62 min. CONCLUSION: DBE-ERCP
      enables us to perform ERC in a group of patients for whom it was impossible
      previously. Further experience is needed to evaluate its therapeutic efficacy
      compared with alternative methods.

PMID- 19585074
TI  - Laparoscopic pancreatic resection: some benefits of evolving surgical techniques.
AB  - Laparoscopic pancreatic resection began to be reported in the first half of the
      1990s, with subsequent reports focusing primarily on the safety and usefulness of
      laparoscopic distal pancreatectomy (Lap-DP) for benign and low-malignancy lesions
      of the pancreatic body and tail (such as chronic pancreatitis, neuroendocrine
      tumor, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm).
      Recently we have also begun to see retrospective case-control studies comparing
      these techniques with open surgery, with Lap-DP showing advantages not only in
      terms of esthetics related to the surgical wound, but also with regard to reduced
      intraoperative bleeding, postoperative recovery time, and days of postoperative
      hospitalization. Prospective randomized controlled trials are still needed for
      confirmation, but it appears likely that this technique will become a standard
      surgical procedure for the treatment of diseases of the pancreatic body and tail.
      In contrast, laparoscopic pancreatoduodenectomy (Lap-PD) remains controversial in
      the minds of many pancreatic surgeons. This is primarily due to the difficulty of
      laparoscopic reconstruction following resection. However, there have recently
      been a number of single-center reports on the use of this procedure in at least
      20 patients per center, showing that Lap-PD is associated with considerable
      reduction in intraoperative bleeding. Our own experience has been similar. In
      carefully selected patients, we find Lap-PD to be a useful surgical procedure.

PMID- 19585075
TI  - Comparison and phylogenetic analysis of cowpox viruses isolated from cats and
      humans in Fennoscandia.
AB  - Cowpox virus (CPXV), a member of the genus Orthopoxvirus (OPV), has reservoirs in
      small mammals and may cause disease in humans, felidae and other animals. In this
      study we compared CPXVs isolated from humans and cats in Fennoscandia by
      restriction enzyme and DNA sequence analysis. The HindIII restriction profiles
      clearly distinguished geographically distinct CPXV isolates, whereas only minor
      differences were found between the profiles of geographically linked isolates.
      The complete gene sequences encoding the cytokine response modifier B, the
      hemagglutinin and the Chinese hamster ovary host range protein were determined
      for the same isolates and included in phylogenetic analysis. By including
      representative OPV sequences from GenBank, detailed comparative analyses were
      performed showing pronounced heterogeneity among CPXVs compared to members of
      other OPV species. However, a close relationship between the Norwegian (3 of 4
      isolates) and Swedish isolates was detected, whereas the isolate from Finland was
      more closely related to a Russian isolate for all three genes compared. We infer
      that the investigated CPXVs have distinct evolutionary histories in different
      rodent lineages.

PMID- 19585076
TI  - Variations in the frequencies of torque teno virus subpopulations during HAART
      treatment in HIV-1-coinfected patients.
AB  - Sera from 15 patients coinfected with TTV and HIV-1, collected before and at two
      times after introduction of highly active anti-retroviral therapy (HAART), were
      tested for TTV load and the presence of the five highly divergent TTV
      phylogenetic groups. Seven patients showed a 1-5 log TTV load decrease during
      HAART, while the others did not show significant variations. A decrease in the
      number of coinfecting TTV genogroups was detected in 12 of 15 patients, with the
      mean number of TTV genogroups/patient decreasing from 2.33 before HAART to 1.47
      at the last collect. All five genogroups were less frequently found after
      introduction of HAART. Three hundred sixty-seven TTV clones from four different
      genogroups, derived from two patients, were sequenced. Noticeable fluctuations in
      TTV subpopulation frequencies were observed in both patients analyzed. In
      conclusion, HAART tends to reduce the number of TTV genotypes/genogroups and may
      affect the balance between different TTV isolates coinfecting single individuals.

PMID- 19585077
TI  - Identification of amino acid residues of Ljungan virus VP0 and VP1 associated
      with cytolytic replication in cultured cells.
AB  - Ljungan virus is a picornavirus isolated from Swedish and North American rodents.
      Replication of Ljungan virus in cultured cells normally induces a weak and
      delayed cytopathic effect compared to that of many other picornaviruses. However,
      efficiently replicating Ljungan virus variants may evolve during serial passages
      in cell culture. In this study, we evaluate the significance of three
      substitutions in capsid protein VP0 and VP1 of a cell-culture-adapted variant of
      the Swedish Ljungan virus 145SL strain. In contrast to the parental strain, this
      145SLG variant grows to high titers in green monkey kidney cells and induces a
      distinct cytopathic effect. Reverse genetic analyses demonstrated that each one
      of the individual capsid substitutions contributes to lytic replication in cell
      culture, but also that expression of all three substitutions results in a 100- to
      500-fold increase in viral titers compared to viruses encoding single capsid
      substitutions. In addition, as indicated by detection of activated caspase-3 and
      DNA fragmentation, there seems to be an association between increased replication
      efficiency of lytic Ljungan virus variants and induction of an apoptotic response
      in infected green monkey kidney cells.

PMID- 19585078
TI  - Stereoanesthesia or astereognosia?
AB  - This case attempts to explicit the importance of clinical examination in the
      differential diagnosis of two similar clinical entities namely astereognosia and
      stereoanesthesia. The patient presented below involves a multiple sclerosis
      patient whose symptoms were considered at first to be a case of astereognosia
      since she mainly complained of an inability to recognize and name the form and
      nature of objects by touch. However, a thorough clinical examination and the
      results of neurophysiological and neuroimaging testing demonstrated that it
      involved a case of stereoanesthesia due to a demyelinating lesion at the cervical
      region of the spinal cord.

PMID- 19585079
TI  - Susceptibility of Staphylococcus aureus to porphyrin-mediated photodynamic
      antimicrobial chemotherapy: an in vitro study.
AB  - The ability of Staphylococcus aureus to develop multidrug resistance is well
      documented, and the antibiotic resistance showed by an increasing number of
      bacteria has shown the need for alternative therapies to treat infections,
      photodynamic therapy (PDT) being a potential candidate. The aim of this study was
      to determine the effect of photodynamic therapy as a light-based bactericidal
      modality to eliminate Staphylococcus aureus. The study investigated a technique
      based on a combination of light and a photosensitizer that is capable of
      producing oxidative species to induce a cytotoxic effect. A Staphylococcus aureus
      suspension was exposed to a light emitting diode (LED) emitting at 628 nm, 14.6
      mW/cm(2), and energy density of 20 J/cm(2), 40 J/cm(2), or 60 J/cm(2) in the
      presence of different porphyrin concentrations (Photogem). Three drug
      concentrations were employed: 12 microl/ml, 25 microl/ml, and 50 microl/ml. The
      treatment response was evaluated by the number of bacterial colony forming units
      (CFU) after light exposure. The results indicated that exposure to 60 J/cm(2)
      eliminated 100% (10 log(10) scales) of bacteria, on average. The best PDT
      response rate to eliminate Staphylococcus aureus was achieved with exposure to
      LED light in combination with the photosensitizer at concentrations ranging from
      25 microl/ml to 50 microl/ml. These data suggest that PDT has the potential to
      eliminate Staphylococcus aureus in suspension and indicates the necessary drug
      concentration and light fluency.

PMID- 19585081
TI  - TULA-family proteins: an odd couple.
AB  - Two members of the TULA family (TULA/STS-2/UBASH3A and TULA-2/STS-1/UBASH3B)
      recently emerged as novel regulators of several cellular functions. The degree of
      structural similarity between the TULA-family proteins is typical for proteins
      that belong to the same family. Furthermore, the experiments with knockout mice
      lacking these proteins may be interpreted as suggesting that functions of TULA
      family proteins in T lymphocytes overlap. At the same time, TULA and TULA-2
      exhibit clear functional dissimilarities, starting with the finding that a
      conserved phosphatase domain present in both proteins exhibits remarkable
      differences in enzymatic activity; TULA-2 is an active phosphatase capable of
      dephosphorylating multiple tyrosine-phosphorylated proteins, whereas the
      phosphatase activity of TULA is extremely low. In contrast, TULA, but not TULA-2,
      facilitates growth factor withdrawal-induced apoptosis in T cells. In spite of
      their apparent importance, the functional role of TULA-family proteins is not
      well understood. In particular, the role of functional dissimilarities between
      them remains unclear.

PMID- 19585082
TI  - Influence of prolonged exposure of a short half life non-steroidal anti
      inflammatory drugs on gastrointestinal safety.
AB  - AIMS: To test the influence of frequent concentration peaking, as occurs in
      multiple-dosing of non-steroidal anti-inflammatory drugs (NSAIDs) with short t
      (1/2), and duration of therapy of NSAIDs on gastrointestinal permeability.
      METHODOLOGY: 2.5 mg/(kg 12 h) flurbiprofen was administered as repeated oral and
      interperitoneal (i.p) doses or as i.p. osmotic pump (once implanted to mimic long
      t(1/2)) for 7 days to healthy rats. Urinary excretion of (51)Cr-EDTA (days 0, 1,
      4 and 7 during all regimens) and sucrose (days 0, 1 and 7 for i.p. doses) were
      measured as markers of gastroduodenal and intestinal permeability, respectively.
      RESULTS: Both i.p. regimens elevated (51)Cr-EDTA permeability suggestive of a
      systemic effect. There was no significant difference between the i.p regimens in
      (51)Cr-EDTA permeability. The first day (51)Cr-EDTA permeability was
      significantly higher for the oral than for the i.p. doses suggestive of a topcal
      effect. The effect became less potent with time despite continuous dosing
      indicating adaptation for both topical and systemic effects. None of the i.p.
      regimen altered sucrose permeability. CONCLUSION: NSAID's potency to increase
      permeability reduces with time despite continuous dosing. Topical effect
      following oral dosing, and not the frequent peaking differentiates regimens from
      each other in elevating (51)Cr-EDTA permeability. The repeated dosing rather than
      the magnitude of t(1/2) may influence the gut safety profile of NSAIDs.

PMID- 19585080
TI  - Predominant regulators of tubulin monomer-polymer partitioning and their
      implication for cell polarization.
AB  - The microtubule-system organizes the cytoplasm during interphase and segregates
      condensed chromosomes during mitosis. Four unrelated conserved proteins,
      XMAP215/Dis1/TOGp, MCAK, MAP4 and Op18/stathmin, have all been implicated as
      predominant regulators of tubulin monomer-polymer partitioning in animal cells.
      However, while studies employing the Xenopus egg extract model system indicate
      that the partitioning is largely governed by the counteractive activities of
      XMAP215 and MCAK, studies of human cell lines indicate that MAP4 and Op18 are the
      predominant regulators of the interphase microtubule-array. Here, we review
      functional interplay of these proteins during interphase and mitosis in various
      cell model systems. We also review the evidence that MAP4 and Op18 have
      interphase-specific, counteractive and phosphorylation-inactivated activities
      that govern tubulin subunit partitioning in many mammalian cell types. Finally,
      we discuss evidence indicating that partitioning regulation by MAP4 and Op18 may
      be of significance to establish cell polarity.

PMID- 19585085
TI  - Biophysical characterization of beta-thalassemic red blood cells.
AB  - Thalassemia is the world's most common hereditary disease; therefore, more
      interest has been devoted for the development of the screening procedure of this
      disease. In beta-thalassemia major, the subject of the current study, impaired
      biosynthesis of beta-globin leads to accumulation of unpaired alpha-globin chain.
      The objective of the present study, was to examine many of the biophysical
      properties of beta-thalassemia major red blood cells (RBCs) and to study the
      possibility of use of any of them as a preliminary screening tool for beta
      thalassemia. The percentage of normal hemolysis, osmotic fragility test,
      turbidity test, rheological properties, and dielectric properties, were studied
      in 20 regularly blood transfused thalassemia major patients who were under
      chelation therapy and their status were compared with those of 10 healthy
      subjects. There was an increase in the percentage of hemolysis for beta
      thalassemia by 114.6% compared to the normal RBCs. The fragility curve for beta
      thalassemia RBCs showed a shift toward lower NaCl concentration compared to the
      normal curve. The average osmotic fragility (H(50): the NaCl concentration
      producing 50% homolysis) for beta-thalassemia was found to be 3.21 +/- 0.67 g/l,
      whereas for normal RBCs it was 5.5 +/- 0.31 g/l. The turbidity curve of the beta
      thalassemic RBCs showed a shift toward higher detergent concentration of the
      normal curve, with higher value for the average membrane solubilization (S(50)).
      The viscosity value of whole blood beta-thalassemia was found to be 3.916 +/-
      0.56 cp whereas for normal blood was 2.516 +/- 0.36 cp. The relative
      permittivity, dielectric loss, and AC conductivity of RBCs decreased
      significantly compared to normal samples. This could be attributed to the loss of
      the insulating properties of the membrane and loss of its surface charge of
      thalassemic RBCs. As can be noticed, several factors showed clear difference
      between thalassemic and normal blood samples. Some of these parameters could be
      measured immediately after sample withdrawal and require short time to perform
      the measurements. This offers the advantages of being effective, low cost, and
      fast techniques, therefore, we suggest that these techniques could be applied for
      beta-thalassemia major screening purposes.

PMID- 19585084
TI  - Knowing when to give up: early-rejection stratagems in ligand docking.
AB  - Virtual screening is an important resource in the drug discovery community, of
      which protein-ligand docking is a significant part. Much software has been
      developed for this purpose, largely by biochemists and those in related
      disciplines, who pursue ever more accurate representations of molecular
      interactions. The resulting tools, however, are very processor-intensive. This
      paper describes some initial results from a project to review computational
      chemistry techniques for docking from a non-chemistry standpoint. An abstract
      blueprint for protein-ligand docking using empirical scoring functions is
      suggested, and this is used to discuss potential improvements. By introducing
      computer science tactics such as lazy function evaluation, dramatic increases to
      throughput can and have been realized using a real-world docking program.
      Naturally, they can be extended to any system that approximately corresponds to
      the architecture outlined.

PMID- 19585083
TI  - A phase I pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic
      agent, in patients with refractory solid cancer.
AB  - We conducted a phase I trial of the antiangiogenic agent 6-O-(4
      dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to
      determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety
      profiles as well as identify the biologically active dose (BAD) from ex vivo
      pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation
      schedule, 19 patients with refractory solid tumors were enrolled at dose levels
      of CKD-732 ranging from 1 to 15 mg/m(2) given twice weekly for 2 weeks followed
      by a 1-week rest. No treatment-related deaths occurred in this study. Confusion
      and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m(2). The
      area under the concentration-time curve (AUC) and maximum concentration (Cmax)
      increased dose dependently with increasing doses. The BAD was 5 mg/m(2) according
      to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor
      3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P =
      0.045). The results from this study showed an MTD of 15 mg/m(2) and a BAD of 5
      mg/m(2).

PMID- 19585086
TI  - [Rectal pocket syndrome after stapled haemorrhoidopexy].
AB  - We report the case of a 41-year-old female patient who presented in the emergency
      department with recurrent pain in the lower abdomen 3 years after
      haemorrhoidopexy (Longo's procedure). At clinical examination a space-occupying
      mass between the rectum and the vagina was present which was identified as a
      stool-loaded diverticulum of the rectum by magnetic resonance imaging. Using a
      perineal approach the diverticulum could be excised at its base and the defect of
      the mucosa was closed transanally with sutures. A diverticulum of the rectum is a
      rare complication (2.5%) after stapled haemorrhoidopexy. In the diagnostic of
      complications after Longo's haemorroidopexy the MRI constitutes an excellent
      auxiliary modality.

PMID- 19585087
TI  - [Intramedullary stabilization of bilateral femur fractures with pulmonary artery
      embolism].
AB  - This is a case report of a 31-year-old motorcyclist who was admitted to our
      emergency department with severe multiple injuries and an ISS score of 38
      points.There were bone injuries on all 4 extremities, fractures of both proximal
      femurs, both radii, a great soft tissue injury of the lower limb, stable
      fractures of the spine and a blunt thoracic injury. A bone fragment compressed
      femoral vein and artery on the right side with consecutive thrombus in the
      inferior caval vein and thrombembolism of the central lung artery. The proximal
      femur fractures were treated initialy with gamma-nails after implanting a cava
      filter because of the high-risk constellation for further thrombembolism.
      Operation was monitored with transesophageal echocardiography.The cava filter
      could be delivered on 2nd postoperative day without complication. The patient was
      ventilated for 1 day, stayed on ICU for 9 days and left hospital in a good
      condition after 28 days. It was the strategic and logistic great achievement of
      an interdisciplinary trauma center to implant cava filter and decide for
      intramedullar osteosythesis without delay.

PMID- 19585088
TI  - [Therapy principles of distal fractures of the forearm in childhood].
AB  - Fractures of the forearm in children represent one of the most frequent injuries.
      Most are monotraumatic occurring during sport or leisure activities. Diagnosis
      can be made by conventional X-ray examination in 2 planes. Distal forearm
      fractures are classified into epiphyseolysis and epiphyseal fractures,
      metaphyseal greenstick and buckle fractures, complete distal radius and forearm
      fractures as well as Galeazzi lesions. The vast majority of cases without
      relevant dislocation can be treated with immobilization employing a cast. The
      remaining fractures have to be repositioned and restored depending on age and
      degree of dislocation.The state of the art in surgical therapy is the Kirschner
      wire osteosynthesis after closed reduction. Especially meta-diaphyseal fractures
      can alternatively be stabilized with plate osteosynthesis or external fixation.
      Following these therapeutic principles, prognosis is excellent and most of the
      injuries heal without any functional impairment.

PMID- 19585089
TI  - [Fast track in cardiac surgery].
AB  - Fast track in cardiac surgery is not well defined. In the past early or immediate
      extubation was used as a marker. After cardiac surgery this parameter is not
      sufficient. In addition to cardiorespiratory stability, circulatory and
      haemostatic homeostasis are also required. Therefore the current Fast Track
      concept includes a period of intensive monitoring of the patient postoperatively
      to establish stability. Thereafter intensive care medicine should not be
      required. Evolving new surgical concepts in combination with appropriate
      anaesthesiologic management will lead to wide application of fast track cardiac
      surgery in the future.

PMID- 19585090
TI  - [Cluster immunotherapy of persistent allergic rhinoconjunctivitis. Safety aspects
      of induction therapy with mite depot allergen preparations].
AB  - BACKGROUND: Apart from allergen avoidance and pharmacotreatment, specific
      immunotherapy (SIT) is the most important therapeutic option offered to allergic
      patients. Clinical efficacy of SIT depends on the specific allergen extract used,
      the quality and total cumulative amount of allergen applied and the treatment
      schedule of the therapy. In cluster SIT, 2-3 injections per treatment day are
      applied resulting in an accelerated achievement of the maintenance dose. PATIENTS
      AND METHODS: In this study 79 mite-sensitized adult allergic patients aged 18 to
      59 years (mean 27.4+/-7.2 years) were investigated in terms of side-effects of
      cluster SIT during induction treatment. RESULTS: A total of 129 local
      hypersensitivity reactions (>grade 1) occurred or 10.2% of all injections (69%
      grade 1, 20% grade 2, 11% grade 3 and no grade 4 reactions). The total number of
      systemic reactions was 40 or 3.2% of all injections with 92% grade 1 and 8% grade
      2 reactions. Grade 3 or 4 reactions did not occur. CONCLUSION: Cluster SIT with
      depot allergens represents an interesting alternative option to conventional
      dosage schedules of SIT.

PMID- 19585091
TI  - Trends in research related to "Shinrin-yoku" (taking in the forest atmosphere or
      forest bathing) in Japan.
AB  - "Shinrin-yoku", which can be defined as "taking in the forest atmosphere or
      forest bathing", has been receiving increasing attention in Japan in recent years
      for its capacity to provide relaxation and reduce stress. Since 2004, the authors
      of this paper have been involved in an investigation designed to ascertain the
      physiological effects of "Shinrin-yoku" within the framework of the "Therapeutic
      Effects of Forests" project. We have conducted physiological experiments, both in
      actual forests and in the laboratory, to elucidate the physiological effects on
      individuals of exposure to the total environment of forests or to only certain
      elements of this environment, such as the odor of wood, the sound of running
      stream water, and the scenery of the forest. We have obtained physiological
      measurements of central nervous activity, autonomic nervous activity, and
      biomarkers reflecting stress response that can be applied in this line of
      approach. Using these measurements, we have summarized the separate elements of
      forests in terms of the five senses. We have also reviewed a selection of field
      studies and introduced a number of results from ongoing projects as well as those
      from early studies. Future perspectives are also discussed.

PMID- 19585092
TI  - [Peripheral arterial disease: epidemiology, symptoms and diagnosis].
AB  - Peripheral arterial disease (PAD) is highly prevalent. Patients with PAD have
      often manifestations of atherosclerosis in other vascular territories and are at
      increased risk for cardiovascular events. Typical symptoms are intermittent
      claudication or rest pain and acral lesions in patients with advanced PAD. The
      majority of PAD patients is clinically asymptomatic, therefore it makes sense to
      look for PAD in patients with cardiovascular risk factors. The ankle brachial
      index (ABI = ankle/arm pressure) is regarded as an easy and cost effective method
      for baseline diagnostic. If ABI measurement confirms the suspected PAD, a
      detailed diagnostic pathway should follow in which duplex sonography plays a
      central role. In some cases additional radiologic imaging is necessary to
      complete the diagnostic or to plan therapeutic procedures.

PMID- 19585093
TI  - [30 year-old patient with multiple pelvic lesions and fecal incontinence].
AB  - In a 30 year-old patient with subacute loss of bowel control and perianal
      anesthesia radiologic examination showed multiple bone lesions. The results of a
      bone marrow aspiration showed acute myeloid leukemia M2 with translocation
      t(8,21) associated with granulocytic sarcoma. The patient was treated with high
      dose chemotherapy and had a complete remission after autologous stem cell
      transplantation.

PMID- 19585094
TI  - [Pathophysiology of the right ventricle in lung diseases].
AB  - The thin-walled right heart is characterized by a low mass-volume-relation. Right
      ventricular function is influenced basically by loading conditions (afterload and
      preload), myocardial perfusion, contractility and heart rate. Afterload is
      determined by intrathoracal and pulmonary vascular pressure/resistance.
      Morphologic adaptions of the right ventricle affect right ventricular function in
      cor pulmonale. So the normal, not hypertrophied right ventricle is extremely
      sensitive to increasing pulmonary artery pressure. Otherwise, minor reductions in
      afterload lead to a substantial decrease of right ventricular wall stress,
      myocardial oxygen demand and likely the risk of arrhythmia. Therefore clinical
      consequences and complications of pulmonary hypertension are substantially
      dependent on right ventricular dynamics.

PMID- 19585095
TI  - [S2 guidelines on diagnostic, therapy and metaphylaxis of urolithiasis. Part 2:
      Metabolic diagnostic and metaphylaxis].

PMID- 19585096
TI  - [S2 guidelines on diagnostic, therapy and metaphylaxis of urolithiasis : Part 1:
      Diagnostic and therapy].

PMID- 19585097
TI  - [Economic aspects of the treatment of urinary stones. Results of the German
      Society for Shock Wave Lithotripsy].
AB  - Urolithiasis is the disease that leads to the largest number of inpatient
      treatments in urologic clinics in Germany. It is very important to know the
      current rules of remuneration for urinary stone therapy and to adjust the
      relevant clinical pathways. The German Society for Shock Wave Lithotripsy (DGSWL)
      stressed these economic aspects at its 2009 consensus meeting, since clinical
      therapy cannot be free of economic restrictions in the long term.

PMID- 19585098
TI  - [The bought patient : The ethical value of per capita flat rates from a medical
      viewpoint].
AB  - Payments received by private physicians per patient sent for hospital treatment
      are a relatively new phenomenon in the German medical system. This practice has
      been made possible by the currently aggressive competition between hospitals. The
      practice of such regular payments has several legal as well as ethical aspects.
      It needs to be clarified whether and in which cases such payments constitute a
      justified fee for a valuable and necessary service or whether they simply
      represent an element of corruption which is used to generate case numbers in a
      competitive market situation.

PMID- 19585099
TI  - Look before you leap: a new approach to mapping QTL.
AB  - In this paper, we present an innovative and powerful approach for mapping
      quantitative trait loci (QTL) in experimental populations. This deviates from the
      traditional approach of (composite) interval mapping which uses a QTL profile to
      simultaneously determine the number and location of QTL. Instead, we look before
      we leap by employing separate detection and localization stages. In the detection
      stage, we use an iterative variable selection process coupled with permutation to
      identify the number and synteny of QTL. In the localization stage, we position
      the detected QTL through a series of one-dimensional interval mapping scans.
      Results from a detailed simulation study and real analysis of wheat data are
      presented. We achieve impressive increases in the power of QTL detection compared
      to composite interval mapping. We also accurately estimate the size and position
      of QTL. An R library, DLMap, implements the methods described here and is freely
      available from CRAN ( http://cran.r-project.org/ ).

PMID- 19585100
TI  - Ryd4 (Hb): a novel resistance gene introgressed from Hordeum bulbosum into barley
      and conferring complete and dominant resistance to the barley yellow dwarf virus.
AB  - Barley yellow dwarf virus (BYDV) causes high yield losses in most of the major
      cereal crops worldwide. A source of very effective resistance was detected within
      the tetraploid wild species of Hordeum bulbosum. Interspecific crosses between a
      resistant H. bulbosum accession and H. vulgare cv. 'Igri' were performed to
      transfer this resistance into cultivated barley. Backcrosses to H. vulgare
      resulted in offspring which carried a single subterminal introgression of H.
      bulbosum chromatin on barley chromosome 3HL and proved to be fully resistant to
      BYDV-PAV, as inferred by ELISA values of zero or close to zero and lack of BYDV
      symptoms. Genetic analysis indicated a dominant inheritance of the BYDV-PAV
      resistance factor, which we propose to denote Ryd4 ( Hb ) . The identity and
      effect of Ryd4 ( Hb ) are discussed in relation to other known genes for BYDV
      resistance or tolerance, as well as the relevance of this gene for resistance
      breeding in barley.

PMID- 19585101
TI  - A susceptibility gene for type 2 diabetes confers substantial risk for diabetes
      complicating cystic fibrosis.
AB  - AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with
      cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent
      heritability studies in CF twins and siblings indicate that genetic modifiers
      play a substantial role. We sought to assess whether genes conferring risk for
      diabetes in the general population may play a risk modifying role in CF. METHODS:
      We tested whether a family history of type 2 diabetes affected diabetes risk in
      CF patients in 539 families in the CF Twin and Sibling family-based study. A type
      2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was
      evaluated for association with diabetes in CF using 998 patients from the family
      based study and 802 unrelated CF patients in an independent case-control study.
      RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF
      (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T
      allele at rs7903146) was associated with diabetes in CF in the family study (p =
      0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the
      family-based study, variation in TCF7L2 increased the risk of diabetes about
      three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the
      mean age at diabetes diagnosis by 7 years. In CF patients not treated with
      systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per
      allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic
      variant conferring risk for type 2 diabetes in the general population is a
      modifier of risk for diabetes in CF.

PMID- 19585102
TI  - Avoidance of patellar eversion improves range of motion after total knee
      replacement: a prospective randomized study.
AB  - Minimally invasive surgery has recently been introduced in TKA surgery. The
      purpose of this study was to evaluate the effect of eversion of the patella, on
      safety and functional result after TKA. In a prospective, randomised, double
      blinded trial, 60 patients were divided in two groups: group A underwent TKA
      through a standard medial parapatellar arthrotomy, with patellar eversion. Group
      B underwent the same exposure, except for the fact that the patella was subluxed
      laterally. All other treatment protocols were identical. Outcomes were measured
      until 1 year postoperatively. Radiographic evaluation included AP, lateral,
      skyline and full leg standing radiographs. VAS, WOMAC score, Knee Society Knee
      and Function score were performed. Active and passive range of motion (ROM) and
      knee proprioception was measured. All patients underwent isokinetic strength
      testing. The mean passive ROM changed from 121 degrees preoperatively to 121
      degrees postoperatively in group A, compared to 118 degrees -131 degrees
      respectively in group B at 1 year (P = 0.003). The mean active ROM changed from
      112 degrees to 115 degrees in group A, and from 108 degrees to 125 degrees in
      group B (P = 0.005). All other parameters were not significantly different.
      Patellar dislocation without eversion for exposing the knee during TKA is a safe
      procedure and improves ROM at 1 year postoperatively.

PMID- 19585103
TI  - Anatomic double-bundle ACL reconstruction using a bone-patellar tendon-bone
      autograft: a technical note.
AB  - This article describes an original arthroscopic double-bundle anterior cruciate
      ligament (ACL) reconstruction technique using a bone-patellar tendon-bone
      autograft. A rectangular patellar bone block, with a double strand patellar
      tendon, and a double tibial bone block is harvested. The femoral anteromedial
      tunnel is made using an all-inside technique by the anteromedial portal. The
      femoral posterolateral (PL) tunnel is created with an outside-in technique, with
      a 30 degrees divergence between both tunnels. A single tibial tunnel is drilled,
      the graft is then passed through the tibial tunnel, and the bundles are
      separately tensioned and fixed with three bioabsorbable interference screws. The
      femoral AM bone block is fixed by the anteromedial portal, the tibial bone block
      is then fixed in an oblique manner in order to mimic the ACL orientation with the
      knee at 30 degrees of flexion. The femoral PL bone block is fixed at the end with
      the knee in full extension.

PMID- 19585104
TI  - The injury profile of Karate World Championships: new rules, less injuries.
AB  - The aim of this paper is to document the injury rate in high-level modern
      competitive karate after a change of competition rules was implemented in the
      year 2000, and to compare it with the injury rate found before the rules were
      changed. A prospective recording of the injuries resulting from 2,762 matches in
      three consecutive World Karate Championships (representing 7,425 min of active
      fighting) was performed, and compared with the results from 2,837 matches from
      the three last World Karate Championships (representing 7,631 min of active
      fighting) held before the change of competition rules. In total, 497 injuries
      were recorded, with an incidence of 0.180 injuries per match or 6.7 per 100 min
      of active fighting. There were 1,901 male category fights (in which 383 injuries
      were recorded), and 861 female category fights (in which 114 injuries were
      recorded). The global injury incidence was almost double with the old rules
      compared to the one with the new rules [OR 1.99, 95% CI (1.76-2.26); p <
      0.00001]. In male category, the risk of injury was higher before the rules were
      changed [OR 1.81, 95% CI (1.56-2.09); p < 0.00001], and also in female category
      [OR 2.71; 95% CI (2.64-2.80); p < 0.00001]. The rate of severe injuries was not
      different before and after the change of rules. The implementation of the new
      competition rules in competitive karate has been associated with a significant
      reduction in injury rate, making competition safer for athletes.

PMID- 19585105
TI  - Selective anteromedial bundle reconstruction in partial ACL tears: a series of 36
      patients with mean 24 months follow-up.
AB  - The purpose of this study was to describe an original technique of reconstruction
      of the anteromedial bundle preserving the posterolateral bundle and to report the
      results of a consecutive 36 patients series with mean 24 months follow-up. Our
      hypothesis is that this selective reconstruction of ACL partial tears could
      restore knee stability and function. In a consecutive series of 256, ACL
      reconstructions, 36 patients in which intact ACL fibers remained in the location
      corresponding to the posterolateral bundle were perioperatively diagnosed. These
      patients (21 women and 15 men) underwent isolated reconstruction of the
      anteromedial bundle while keeping the remaining fibers intact. AM bundle
      reconstructions were performed by the same surgeon using an outside-in technique.
      A quadrupled hamstring graft was used in 20 patients and a doubled semitendinosus
      graft in 16 patients. The mean age of the patients at the time of surgery was 32
      years (min 15, max 53). The delay between injury and surgery was 6.6 months (min
      2, max 35). Patients were assessed with the IKDC ligament evaluation form.
      Instrumented knee testing was performed with the Rolimeter arthrometer.
      Statistical analysis was performed to compare the preoperative and postoperative
      objective evaluation. Eleven concomitant meniscal lesions at the time of
      reconstruction were found. One patient who underwent a traumatic graft rupture at
      4 months post surgery and two patients with previous contralateral ACL
      reconstruction were excluded, leaving 33 patients for final evaluation. Three
      reoperations were performed, including two arthrolysis for cyclops syndrome and
      one revision for a traumatic graft rupture. At last follow-up, 24 (73%) patients
      were graded A, 8 (24%) graded B and 1 C (3%) at IKDC objective evaluation. Mean
      side to side instrumented laxity was 4.8 mm (min 3, max 6) preoperatively and 0.8
      mm (min 0, max 2) postoperatively. AM bundle reconstruction with an outside-in
      technique remains simple and reproducible. The preliminary results are
      encouraging with excellent side to side laxity. Graft size should probably be
      adapted to limit cyclops syndrome occurrence.

PMID- 19585106
TI  - Short-term antidepressant treatment modulates amygdala response to happy faces.
AB  - RATIONALE: We have previously demonstrated that antidepressant medication
      facilitates the processing of positive affective stimuli in healthy volunteers.
      These early effects of antidepressants may be an important component in the
      therapeutic effects of antidepressant treatment in patients with depression and
      anxiety. OBJECTIVES: Here we used functional magnetic resonance imaging in a
      double-blind, randomised, placebo-controlled between-groups design to investigate
      the effects of short-term (7-10 days) treatment with the selective serotonin
      reuptake inhibitor, citalopram, on the amygdala response to positive and negative
      facial expressions in healthy volunteers. RESULTS: Citalopram was associated with
      increased amygdala activation to happy faces relative to placebo control, without
      changes in levels of mood or anxiety. CONCLUSIONS: These early, direct effects of
      antidepressant administration on emotional processing are consistent with a
      cognitive neuropsychological model of antidepressant action.

PMID- 19585109
TI  - In situ measurements of emission transition dipole moment of individual ordered
      microdomain of diprotonated tetraphenylporphine aggregate formed at
      dodecane/aqueous H2SO4 interface.
AB  - Rhombic-ordered microdomains of diprotonated 5,10,15,20-tetraphenylporphine
      aggregate, whose sizes were 10-200 microm, were formed at dodecane/aqueous
      H(2)SO(4) interfaces. The light excitation of their two absorption bands (410 and
      473 nm for H- and J-bands, respectively) led to one fluorescence band at longer
      wavelength (723 nm). The direction of the emission transition dipole moment
      (mu(e)) of individual rhombic microdomains, determined with an in situ optical
      microscope and a linear polarizer, was almost parallel to the major axis, which
      was also almost parallel to the direction of the absorption transition dipole
      moment of their J-bands. Their absorption and emission transition scheme was
      proposed.

PMID- 19585107
TI  - Equivalent effects of acute tryptophan depletion on REM sleep in ecstasy users
      and controls.
AB  - INTRODUCTION: This study sought to test the association between 3,4
      methylenedioxymethamphetamine use, serotonergic function and sleep. MATERIALS AND
      METHODS: Ambulatory polysomnography was used to measure three nights sleep in 12
      ecstasy users and 12 controls after screening (no intervention), a tryptophan
      free amino acid mixture (acute tryptophan depletion (ATD)) and a tryptophan
      supplemented control mixture. RESULTS: ATD significantly decreased rapid eye
      movement (REM) sleep onset latency, increased the amount of REM sleep and
      increased the amount of stage 2 sleep in the first 3 h of sleep. There was no
      difference between ecstasy users' and controls' sleep on the screening night or
      after ATD. DISCUSSION: These findings imply that the ecstasy users had not
      suffered significant serotonergic damage as indexed by sleep.

PMID- 19585110
TI  - Development of a metabonomic approach based on LC-ESI-HRMS measurements for
      profiling of metabolic changes induced by recombinant equine growth hormone in
      horse urine.
AB  - Despite the worldwide existing regulation banning the use of the recombinant
      equine growth hormone (reGH) as growth promoter, it is suspected to be used in
      horseracing to improve performances. Various analytical methods previously
      developed to screen for its misuse have encountered some limitations in terms of
      detection timeframes, in particular during the first days following reGH
      administration. A novel strategy involving the characterization of global
      metabolomic fingerprints in urine samples of non-treated and reGH-treated horses
      by liquid chromatography-electrospray-high-resolution mass spectrometry (LC-ESI
      HRMS) is described and assessed in this paper in order to develop a new screening
      tool for growth hormone abuse in horseracing. The strategy involves a limited
      sample preparation of the urine samples and the use of appropriate software for
      data processing and analysis. As preliminary work, reproducibility of both sample
      preparation and mass spectrometry (MS) measurements was evaluated in order to
      demonstrate the reliability of the method. Application of the developed protocol
      on two horses demonstrated the suitability of the developed strategy and
      preliminary results showed significant modifications of the metabolome after
      treatment with reGH.

PMID- 19585111
TI  - Electrochemical immunoassay using quantum dot/antibody probe for identification
      of cyanobacterial hepatotoxin microcystin-LR.
AB  - The presence of cyanobacterial hepatotoxins such as microcystin-LR poses health
      threats to humans due to their potential for causing severe physiological effects
      when contaminated drinking water is ingested. Here, the electrochemical detection
      of microcystin-LR is explored using a quantum dot/antibody (QD/Ab) probe for
      nanoparticle-based amplification and direct electrochemical transduction. The
      immunological recognition of microcystin-LR using the QD/Ab probe was amplified
      and converted to an electrochemical signal by measuring the cadmium ions released
      from QD based on square wave stripping voltammetry under optimized
      electrochemical factors. Whereas a qualitative analysis for microcystin-LR was
      achieved using the specific peak potential of the anodic voltammogram at -0.6 +/-
      0.05 V, concentration of the toxin was quantified based on the charge density of
      the anodic peak; a dynamic range of 0.227 to 50 microg/L and limit of detection
      of 0.099 microg/L were obtained with high sensitivity. The extracted microcystin
      LR from Microcystis aeruginosa was estimated as 1,944 microg/g of dried weight of
      the microorganism.

PMID- 19585112
TI  - Formation, determination and significance of masked and other conjugated
      mycotoxins.
AB  - Mycotoxins are secondary metabolites of fungi poisonous for humans or animals
      which can be found on a great variety of food and feed commodities. Food is not
      necessarily safe just because the presence of well-known mycotoxins has been
      ruled out, as they might still be there in disguise. Mycotoxins may also occur in
      conjugated form, either soluble (masked mycotoxins) or incorporated
      into/associated with/attached to macromolecules (bound mycotoxins). These
      conjugated mycotoxins can emerge after metabolization by living plants, fungi and
      mammals or after food processing. Awareness of such altered forms of mycotoxins
      is increasing, but reliable analytical methods, measurement standards and
      occurrence and toxicity data are still lacking. In this paper currently known
      conjugated mycotoxins, their formation and determination are reviewed. For the
      latter, liquid chromatography-(tandem) mass spectrometry or ELISA methods are
      employed with or without conversion to the parent mycotoxins. Sample preparation
      to transform the bound forms into soluble forms can involve enzymatic or
      acidic/alkaline treatment. Especially mycotoxins which are in contact with living
      plants in the field are prone to be metabolized. This transformation process is
      not only important regarding food safety but also for the resistance of plants
      towards fungal-induced diseases, such as Fusarium head blight of wheat.

PMID- 19585113
TI  - Characterization and analysis of the regulatory network involved in control of
      lipomycin biosynthesis in Streptomyces aureofaciens Tu117.
AB  - Analysis of the alpha-lipomycin biosynthesis gene cluster of Streptomyces
      aureofaciens Tu117 led to the identification of five putative regulatory genes,
      which are congregated into a subcluster. Analysis of the lipReg1-4 and lipX1
      showed that they encode components of two-component signal transduction systems
      (LipReg1 and LipReg2), multiple antibiotics resistance-type regulator (LipReg3),
      large ATP-binding regulators of the LuxR family-type regulator (LipReg4), and
      small ribonuclease (LipRegX1), respectively. A combination of targeted gene
      disruptions, complementation experiments, lipomycin production studies, and gene
      expression analysis via RT-PCR suggests that all regulatory lip genes are
      involved in alpha-lipomycin production. On the basis of the obtained data, we
      propose that LipReg2 controls the activity of LipReg1, which in its turn govern
      the expression of the alpha-lipomycin pathway-specific regulatory gene lipReg4.
      The ribonuclease gene lipX1 and the transporter regulator lipReg3 appear to work
      independently of genes lipReg1, lipReg2, and lipReg4.

PMID- 19585114
TI  - Efficacy of 18F-FDG PET/CT in the evaluation of patients with recurrent cervical
      carcinoma.
AB  - PURPOSE: Only a limited number of studies have evaluated the efficacy of 18F-FDG
      PET/CT for recurrent cervical carcinoma, which this study seeks to expand upon.
      METHODS: This is a retrospective study of 30 women with cervical carcinoma who
      had a surveillance PET/CT after initial therapy. Sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value were
      calculated using a 2 * 2 contingency table with pathology results (76%) or
      clinical follow-up (24%) as the gold standard. The Wilson score method was used
      to perform 95% confidence interval estimations. RESULTS: The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of PET/CT for the detection of local recurrence at the primary site were 93, 93,
      93, 86, and 96%, respectively. The same values for the detection of distant
      metastases were 96, 95, 95, 96, and 95%, respectively. Seventy-one percent of the
      scans performed in symptomatic patients showed true-positive findings. In
      comparison, 44% of scans performed in asymptomatic patients showed true-positive
      findings. But, all patients subsequently had a change in their management based
      on the PET/CT findings such that the effect was notable. The maximum standardized
      uptake value ranged from 5 to 28 (average: 13 +/- 7) in the primary site and 3 to
      23 (average: 8 +/- 4) in metastases which were significantly different (p =
      0.04). CONCLUSION: This study demonstrates favorable efficacy of 18F-FDG PET/CT
      for identification of residual/recurrent cervical cancer, as well as for
      localization of distant metastases.

PMID- 19585115
TI  - Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled
      octreotate in rats with CA20948 tumours.
AB  - PURPOSE: Peptide receptor radionuclide therapy using beta-emitting radiolabelled
      somatostatin analogues like DOTA,Tyr3-octreotate shows beneficial results in
      patients suffering from somatostatin receptor overexpressing tumours. However,
      after high-dose therapy partial renal reabsorption of radiopeptides may lead to
      nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these
      radiopeptides without affecting tumour uptake. Recently co-administration of
      Gelofusine has been described to have a comparable kidney-protecting effect in
      rats. In the present study optimal dosing of Gelofusine co-administration was
      studied in tumour-bearing rats. METHODS: Doses of 40, 80, 120 or 160 mg/kg
      Gelofusine were co-injected with 15 ug DOTA,Tyr3-octreotate, labelled with 3 MBq
      111In for biodistribution (24 h post-injection, n = 4 per group) and with 60 MBq
      111In for microSPECT imaging experiments at 3, 24 and 48 h post-injection. An
      additional group of rats received 80 mg/kg Gelofusine plus 400 mg/kg lysine co
      injection. Biodistribution studies were performed both in older (475 g) and
      younger (300 g) rats, the latter bearing CA20948 tumours. RESULTS: Co-injection
      of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention
      of 111In-DOTA,Tyr3-octreotate, whereas higher doses further increased the
      reduction to 50-60% in both groups of rats. Combining Gelofusine and lysine
      caused 70% reduction of renal uptake. The uptake of radiolabelled octreotate both
      in somatostatin receptor-expressing normal tissues and tumours was not affected
      by Gelofusine co-injection. CONCLUSION: In rats co-injection of 80 mg/kg
      Gelofusine resulted in maximum reduction of renal retention of 111In-DOTA,Tyr3
      octreotate, which was further improved when combined with lysine. Tumour uptake
      of radiolabelled octreotate was not affected, resulting in an increased tumour to
      kidney ratio.

PMID- 19585116
TI  - Off-line motion correction methods for multi-frame PET data.
AB  - PURPOSE: Patient motion during PET acquisition may affect measured time-activity
      curves, thereby reducing accuracy of tracer kinetic analyses. The aim of the
      present study was to evaluate different off-line frame-by-frame methods to
      correct patient motion, which is of particular interest when no optical motion
      tracking system is available or when older data sets have to be reanalysed.
      METHODS: Four different motion correction methods were evaluated. In the first
      method attenuation-corrected frames were realigned with the summed image of the
      first 3 min. The second method was identical, except that non-attenuation
      corrected images were used. In the third and fourth methods non-attenuation
      corrected images were realigned with standard and cupped transmission images,
      respectively. Two simulation studies were performed, based on [11C]flumazenil and
      (R)-[11C]PK11195 data sets, respectively. For both simulation studies different
      types (rotational, translational) and degrees of motion were added. Simulated PET
      scans were corrected for motion using all correction methods. The optimal method
      derived from these simulation studies was used to evaluate two (one with and one
      without visible movement) clinical data sets of [11C]flumazenil, (R)-[11C]PK11195
      and [11C]PIB. For these clinical data sets, the volume of distribution (VT) was
      derived using Logan analysis and values were compared before and after motion
      correction. RESULTS: For both [11C]flumazenil and (R)-[11C]PK11195 simulation
      studies, optimal results were obtained when realignment was based on non
      attenuation-corrected images. For the clinical data sets motion disappeared
      visually after motion correction. Regional differences of up to 433% in VT before
      and after motion correction were found for scans with visible movement. On the
      other hand, when no visual motion was present in the original data set, overall
      differences in VT before and after motion correction were <1.5 +/- 1.3%.
      CONCLUSION: Frame-by-frame motion correction using non-attenuation-corrected
      images improves the accuracy of tracer kinetic analysis compared to non-motion
      corrected data. Electronic supplementary material The online version of this
      article (doi:10.1007/s00259-009-1193-y) contains supplementary material, which is
      available to authorised users.

PMID- 19585117
TI  - Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human
      hepatocellular carcinoma and on H22 transplanted mice.
AB  - AIM: To investigate the synergistic inhibitory effects of the combination of 5
      fluorouracil (5-FU) with the natural flavanoid oroxylin A on human hepatocellular
      carcinoma cells HepG2 in vitro and on transplanted murine hepatoma 22 (H22)
      tumors in vivo and the preliminary mechanisms. METHODS: The inhibitory effects of
      5-FU combined with the natural flavanoid oroxylin A in vitro were detected by MTT
      assay and the effects in vivo were investigated by transplanted H22 mice model.
      DAPI staining and Annexin V/propidium iodide (PI) double staining were used to
      detect the cell morphological changes and apoptosis. The mRNA levels of thymidine
      synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in HepG2 cells after
      oroxylin A and 5-FU combination treatment were observed by quantitative real-time
      PCR. Western blotting assay was used to reveal the expressions of apoptotic
      inducing proteins P53, cleaved PARP, COX-2, Bcl-2, and pro-caspase3. RESULTS:
      Oroxylin A in combination with 5-FU presented synergistic effect (CI<1) on HepG2
      cells in vitro when the inhibitory rate was higher than 7.5%. The inhibitory rate
      on H22 murine solid tumor in vivo in the combination group was higher than
      monotherapy. 5-FU combined with oroxylin A exerted stronger apoptotic induction
      in HepG2 cells than either single drug treatment. Quantitative real-time PCR
      discovered the downregulation of TS mRNA and DPD mRNA in HepG2 cells after
      combination treatment. Western blotting assay revealed oroxylin A enhanced 5-FU
      induced apoptosis in HepG2 cells by elevating the expressions of apoptotic
      inducing proteins P53 and cleaved PARP and decreasing the expression of apoptotic
      inhibitory proteins COX-2, Bcl-2, and pro-caspase3. CONCLUSION: The anti
      hepatocellular carcinoma effects in vitro and in vivo of 5-FU and oroxylin A
      combinations were synergistic and oroxylin A increased the sensitivity of HepG2
      cells to 5-FU by modulating the metabolic enzymes of 5-FU and apoptotic-related
      proteins.

PMID- 19585118
TI  - Successful treatment of refractory cardiac tamponade due to rheumatoid arthritis
      using pericardial drainage.
AB  - Rheumatoid pericarditis occurs in patients with rheumatoid arthritis (RA).
      However, cardiac tamponade due to rheumatoid pericarditis is rare; we describe a
      case of a 72-year-old man with a 6-year history of rheumatoid arthritis who
      developed rheumatoid pericarditis with recurrent cardiac tamponade. The patient
      experienced relapse of the cardiac tamponade despite treatment with
      pericardiocentesis. Therefore, the patient underwent surgical pericardial
      drainage. The patient was also subsequently treated with increasing doses of
      corticosteroid, methotrexate and leukocytapheresis. These treatments resulted in
      a successful outcome without any complication. This case suggests that in
      addition to immunosuppressive therapy, pericardial drainage should be considered
      in the treatment of life-threatening refractory cardiac tamponade caused by
      rheumatoid arthritis.

PMID- 19585119
TI  - Lower bone mineral density of forearm in postmenopausal patients with
      radiographic hand osteoarthritis.
AB  - The association between clinical parameters and forearm bone mineral density
      (BMD) in postmenopausal females with radiographic hand OA has not been
      determined. We investigated the difference in forearm BMD between radiographic
      hand OA and non-radiographic hand OA, and also the association between clinical
      parameters of patients and the level of forearm BMD. A total of 180
      postmenopausal patients with hand OA were enrolled in this study. We classified
      them into two groups according to the Kellgren-Lawrence (K-L) radiological grade,
      one with radiographic hand OA (K-L grade > or = 2) and the other with non
      radiographic OA (K-L grade < 2) as controls. The number of nodal joints, swollen
      joints and tender joints were determined in the physical examination, and
      measures of BMD (g/cm(2)), Australian Canadian (AUSCAN) OA hand index, grip
      strength, pinch strength, and visual analogue scale (VAS) were also estimated.
      Patients with radiographic hand OA had lower distal radius BMD when compared with
      controls (0.35 +/- 0.06 vs. 0.40 +/- 0.05, P < 0.001). After adjusting for
      variables such as age, menopausal duration, number of nodal joints, and AUSCAN
      function index, the difference in BMD between the two groups was also
      significantly different (0.35 +/- 0.04 vs. 0.38 +/- 0.04, P < 0.001). For
      analysis of risk factors for forearm BMD in hand OA, age and K-L OA grade in
      total hand OA are considered risk factors, whereas age and menopause duration
      contribute to the forearm BMD in radiographic hand OA patients (P < 0.001, P =
      0.002, respectively). The development of osteoporosis at the distal radius in
      radiographic hand OA is associated with older age (OR = 1.216, P = 0.002), lower
      BMI (OR = 0.777, P = 0.004) and lower stiffness in the AUSCAN OA index (OR =
      0.505, P = 0.003). This study shows that the BMD levels of the distal radius in
      patients with radiographic hand OA are significantly lower when compared to those
      of controls. Forearm BMD levels are positively associated with age and K-L
      radiological grade in total hand OA, whereas age and menopausal duration are
      closely related with radiographic hand OA. The presence of osteoporosis in the
      distal radius in radiographic hand OA may be influenced by age, BMI, and
      stiffness on the AUSCAN index.

PMID- 19585121
TI  - Evaluation of computer-aided detection of lesions in mammograms obtained with a
      digital phase-contrast mammography system.
AB  - A computer-aided detection (CAD) system was evaluated for its ability to detect
      microcalcifications and masses on images obtained with a digital phase-contrast
      mammography (PCM) system, a system characterised by the sharp images provided by
      phase contrast and by the high resolution of 25-MUm-pixel mammograms. Fifty
      abnormal and 50 normal mammograms were collected from about 3,500 mammograms and
      printed on film for reading on a light box. Seven qualified radiologists
      participated in an observer study based on receiver operating characteristic
      (ROC) analysis. The average of the areas under ROC curve (AUC) values for the ROC
      analysis with and without CAD were 0.927 and 0.897 respectively (P = 0.015). The
      AUC values improved from 0.840 to 0.888 for microcalcifications (P = 0.034) and
      from 0.947 to 0.962 for masses (P = 0.025) respectively. The application of CAD
      to the PCM system is a promising approach for the detection of breast cancer in
      its early stages.

PMID- 19585120
TI  - Voltage-dependent anion channels: their roles in plant defense and cell death.
AB  - The voltage-dependent anion channels (VDACs), mitochondrial outer membrane
      components, are present in organisms from fungi to animals and plants. They are
      thought to function in the regulation of metabolite transport between
      mitochondria and the cytoplasm. Sufficient knowledge on plant VDACs has been
      accumulated, so that we can here summarize the current information. Then, the
      involvement of mitochondria in plant defense and cell death is overviewed. While,
      in mammals, it is suggested that VDAC, also known as a component of the
      permeability transition pore (PTP) complex formed in the junction site of
      mitochondrial outer and inner membrane, is a key player in mitochondria-mediated
      cell death, little is known about the role of plant VDACs in this process. We
      have shown that plant VDACs are involved in mitochondria-mediated cell death and
      in defense against a non-host pathogen. In light of the current findings, we
      discuss the role of the PTP complex and VDAC as its component in plant pathogen
      defense and cell death.

PMID- 19585122
TI  - Effective dose evaluation of multidetector CT examinations: influence of the ICRP
      recommendation in 2007.
AB  - We compared effective doses for recent computed tomography (CT) examinations
      calculated based on International Commission on Radiological Protection
      publication number 103 (ICRP 103) with those calculated based on ICRP publication
      number 60 (ICRP 60), and considered the usefulness of the effective dose in CT
      dose evaluation. After placing radiophotoluminescence glass dosimeters (RPLDs)
      inside or outside an anthropomorphic phantom, we examined from the chest to the
      pelvis, cardiac, and cranial regions of the phantom. The absorbed dose was
      calculated by multiplying calibrated dose values of RPLD by the mass energy
      coefficient ratio. The effective dose was calculated as the sum total of the
      value for each tissue, which was multiplied by the equivalent dose according to
      the tissue weighting factor recommended in ICRP 103 and ICRP 60. Calculated
      effective doses based on ICRP 103 were different by -11% to +82% compared with
      those based on ICRP 60. The values of absorbed doses for selective tissues were
      relatively higher than the values for the effective dose. The effective dose
      represents only a mean dose value for an average human. Therefore, assessing the
      absolute dose of particular individuals in CT examinations based exclusively on
      the effective dose is not recommended.

PMID- 19585123
TI  - The assessment of intracranial bleeding with virtual unenhanced imaging by means
      of dual-energy CT angiography.
AB  - The purpose of this study was to assess virtual unenhanced brain computed
      tomography (CT) images obtained by dual-energy CT angiography (CTA) for the
      detection of intracranial bleeding. In total, 25 patients were included in the
      study (average age 53.2 years, range 25-75 years, 14 male, 11 female), all with
      intracranial bleeding on unenhanced brain CT and who underwent additional CTA
      performed on a dual-source CT in a dual-energy acquisition mode. The two X-ray
      tubes were operated at 140 and 80 kV, respectively. Data were analyzed using dual
      energy evaluation software. Virtual unenhanced images were calculated by removing
      the relative iodine content from each voxel. The virtual unenhanced images were
      evaluated by a radiologist blinded to the findings of the conventional images
      related to the presence of intracranial bleeding. The image quality and contrast
      to-noise ratio (CNR) between bleeding and brain tissue were assessed. The virtual
      image quality was found to be sufficient in 96%. The agreement in detection of
      intracranial bleeding on virtual and conventional unenhanced images reached 96%
      in per-lesion analysis and 100% in per-patient analysis. The averaged CNR reached
      2.63 in virtual unenhanced images and 3.27 in conventional. Virtual unenhanced
      images are sufficient for the detection of intracranial bleeding.

PMID- 19585124
TI  - [Unclear deterioration of vision after renal transplant].
AB  - A 27-year-old female patient reported a variable but unsatisfactory visual acuity
      which had persisted for several years. The patient had been dependent on dialysis
      from the age of 14 years old and from then on also needed a hearing aid. A kidney
      had been transplanted 5 years ago. The diagnosis was anterior lenticonus due to
      Alport syndrome.

PMID- 19585125
TI  - Melatonin rhythms in the Australian freshwater crocodile (Crocodylus johnstoni):
      a reptile lacking a pineal complex?
AB  - The vertebrate pineal gland is the primary source of melatonin, the rhythmic
      secretion of which is influenced by environmental light and temperature, thereby
      providing animals with information about seasonally changing photoperiod and
      thermoperiod. Although pineal glands are present in the majority of vertebrate
      species, a discrete organ is reported to be absent in the Crocodilia. However, if
      the melatonin rhythm is crucial to the survival of the organism, it would be
      expected that the rhythm would be present in crocodiles. In the present study, we
      measured blood plasma melatonin over a 30-h period in aestivating Australian
      freshwater crocodiles (Crocodylus johnstoni) in their natural habitat at the end
      of the dry season (November) and found no discernible melatonin rhythm. However,
      another group of captive-reared C. johnstoni, maintained under natural light and
      temperature cycles and sampled in the early dry season (June) showed a clear
      melatonin rhythm. These results suggest that there is either an extrapineal
      source of melatonin in this crocodile species or that there is melatonin
      producing tissue elsewhere which heretofore has not been discovered. Further
      studies are needed to determine why the melatonin rhythm is intermittently
      expressed and whether this may be related to seasonal changes in the expression
      of the rhythm linked to tropical environments.

PMID- 19585128
TI  - Post CSF shunting Chiari I malformation--sequel or complication? Hypertension or
      hypotension?

PMID- 19585126
TI  - Infantile encephalopathy due to vitamin deficiency in industrial countries.
AB  - INTRODUCTION: Severe avitaminosis causing life-threatening conditions in the
      infantile age group is extremely uncommon and has been reported in babies with
      malabsorption receiving prolonged inadequate vitamin supplements. CASE REPORTS:
      We report two infants who presented with neurological deterioration. Immediate
      work-up and treatment for infectious and inborn metabolic disorders were
      initiated and the diagnosis, made with a few days delay, was prolonged
      avitaminosis of thiamine (B1) and cobalamin (B12). B1 deficiency was suspected
      when further neurological deterioration was observed during administration of
      intravenous fluids containing glucose in an infant with high lactate levels in
      the cerebrospinal fluid. High transketolase activity that normalized after
      thiamine treatment and the findings in the MRI and MRS of the brain confirmed the
      suspected diagnosis. B12 deficiency was suspected in an infant of a strict
      vegetarian mother who presented with neurological deterioration and severe
      megaloblastic anemia. The diagnosis was confirmed when low serum levels of B12
      and methylmalonic aciduria were detected and treatment with B12 resulted in
      normalization of urinary methymalonic acid. CONCLUSION: Avitaminosis, even in
      industrialized countries, should be considered in an atypical age group with no
      known risk factors. Early diagnosis and prompt treatment may accomplish a quick
      recovery with fewer sequelae.

PMID- 19585129
TI  - Gradual and complete delivery of a hydatid cyst of the brain through a single
      burr hole, a wrong happening!
AB  - INTRODUCTION: Cerebral hydatidosis is a rare larval infection of the central
      nervous system affecting mostly the children and young adults. CASE REPORT: The
      authors report a case of a 5-year-old girl harboring a large right frontoparietal
      hydatid cyst. The imaging studies were not diagnostic for 'cerebral hydatidosis'
      and were interpreted as 'brain abscess'. DISCUSSION: Attempting for simple
      cannulation of the lesion through a burr hole drained a clear fluid. The cannula
      was removed promptly but the cyst wall came out little by little through the hole
      in a single piece which turned out to be the entire wall of a hydatid cyst. She
      was treated by antihelmintic medications for 6 months and there has been no sign
      of recurrence after a year. Odd paraclinical imaging characteristics and unique
      accidental surgical event makes this case the first reported pediatric brain
      hydatidosis with spontaneous complete delivery of the cyst through a single burr
      hole which can certainly be considered a wrong attempt if undertaken
      intentionally.

PMID- 19585130
TI  - The International Society for Pediatric Neurosurgery: our mission under
      challenge.

PMID- 19585131
TI  - [Tissue retention of T cells as a therapeutic target in rheumatoid arthritis].
AB  - Autoreactive T cells are instrumental for the induction and chronification of
      autoimmune diseases. While immigration of T cells into inflamed tissue is
      strongly enhanced during acute inflammatory phases, retention of antigen specific
      T cells rather than subsequent recruitment of recirculating effector cells
      appears to contribute to the inflammatory infiltrate seen during chronic
      inflammation. Patients suffering from rheumatoid arthritis also show accumulation
      of oligoclonal T cells within the inflamed synovia, where environmental signals
      seem to promote the prolonged survival of these chronically activated T cells.
      The survival signals and mechanisms controlling retention of T cells within the
      inflamed synovia are poorly characterized. However, the specific interference
      with these mechanisms could be a therapeutic approach in chronic inflammatory
      diseases like rheumatoid arthritis that are accompanied by a strong local
      accumulation of immune cells.

PMID- 19585132
TI  - [Biological switches: the 'all-or-none' principle in T-cell activation].
AB  - T helper lymphocytes (Th cells) play a central role in cellular defence against
      pathogens as well as in cellular self tolerance. The activation of Th cells is a
      crucial process determining the course of a protective immune response.
      Dysregulated activation processes can lead to pathologic immune reactions and may
      induce autoimmune diseases. Thus, for example, chronic activation of Th cells can
      trigger autoimmune diseases such as rheumatoid arthritis. One fundamental feature
      of antigen-specific T-cell activation is the synthesis of cytokines, e.g.
      Interleukin- (IL-)2. Here we present results of our working group indicating for
      the first time that, at the level of the individual cell, IL-2 is expressed in a
      binary fashion, i.e. according to an all-or-none principle. The identification
      and characterization of such intracellular switches may provide new options to
      manipulate the fate of T cells and develop novel therapeutic strategies.

PMID- 19585133
TI  - [Myalgia in polymyalgia rheumatica, temporal arteritis and other vasculitides].
AB  - Myalgias most commonly occur in polymyalgia rheumatica (PMR). About 45% of
      patients with giant cell arteritis present with symptoms of PMR. Other
      vasculitides may also lead to arthralgia and myalgia. While shoulder and pelvic
      pain is characteristic for PMR pain often also occurs in the back of the neck and
      in the region of the thoracic spine. In addition, patients often present with
      malaise, morning stiffness and weight loss. CRP and ESR are elevated. Ultrasound
      and MRI delineate minor synovitis, tenosynovitis and bursitis in the shoulder.
      Hip joint synovitis and trochanteric bursitis are also commonly seen. PMR should
      be distinguished from rheumatoid arthritis. The initial treatment comprises a
      prednisolone dose of 15-25 mg/day, followed by a weekly decrease of 1-2.5 mg.
      Once 10 mg/day has been reached the dose should be reduced more slowly.

PMID- 19585134
TI  - Rosette-forming glioneuronal tumor: report of an unusual case with
      intraventricular dissemination.
AB  - A rosette-forming glioneuronal tumor (RGNT) was encountered in a 16-year-old
      Chinese girl. She experienced seizures with loss of consciousness for 1 month
      prior to diagnosis. A brain MRI revealed multifocal masses occupying all of the
      ventricular system associated with marked hydrocephalus. A biopsy was performed
      on the right lateral ventricle using a neuroendoscope and the patient was given
      postoperative radiotherapy. She was followed for 7 months, and there was no
      radiological or clinical evidence of tumor progression. Histological examination
      demonstrated two regions characterized by predominant neurocytic rosettes and
      scant low grade astrocytoma. No histological anaplasia was present.
      Immunohistological studies showed that the small round tumor cells forming
      rosettes were strongly positive for Olig2. A chromosome 1p/19q co-deletion was
      not detected by FISH analysis. While the pathological features of our case
      closely resembled those reported in the original description, the diffuse
      intraventricular growth pattern of the tumor was different from previous
      examples. Further long-term follow-up studies are required to assess the
      biological behavior and clinical outcome of the RGNT entity.

PMID- 19585135
TI  - Post-hysterectomy menstruation: a rare phenomenon.
AB  - Post-menopausal bleeding is a common problem with varied etiology in the age
      group between 50 and 60 years. It is more likely to be of some pathologic cause
      which needs to be ruled out. Bleeding in a patient after hysterectomy is even
      rarer with varied causes like atrophic vaginitis, cervical stump cancer,
      infiltrating ovarian tumors, estrogen secreting tumors in other parts of the
      body. Endometriosis of the vault sometimes can cause post-menopausal bleeding.
      Diverticulitis of the bowel may give rise to vaginal discharge due to fistula,
      but bleeding is rare. Bladder pathology may cause vaginal bleeding. Our case is a
      rare case of vault endometriosis and should always be kept as a differential
      diagnosis in patients with bleeding after hysterectomy.

PMID- 19585136
TI  - Different HLA-DR expression in endometriotic and adenomyotic lesions: correlation
      with transvaginal ultrasonography findings.
AB  - OBJECTIVE: Human leukocyte antigen-DR (HLA-DR) has been implicated in eutopic and
      ectopic glandular epithelial cells in endometriosis. We investigated the
      expression of HLA-DR in endometriotic and adenomyotic tissues within the stromal
      and glandular cells. Moreover, we correlate the HLA-DR expression according the
      transvaginal ultrasonography findings. METHODS: We studied operative and
      pathologic reports of 113 women who underwent laparoscopic or laparotomy
      treatment of endometrioma or adenomyosis. Tissues from 51 women with endometrioma
      and 62 women with adenomyosis were retrospectively evaluated. The distribution
      and intensity of the HLA-DR immunostaining was assessed using electron
      microscopy. Pathologic finding of the uterine junction zone and the size of
      endometrioma were evaluated with the laparoscopic results and the ultrasound
      findings. RESULTS: In adenomyosis tissues, the percentage of HLA-DR cells
      expression was significantly higher in stromal cells (83.9%) compared to
      glandular cells (25.8%), (p<0.001). The number of HLA-DR-positive endometriotic
      glandular cells was significantly higher than the total glandular adenomyotic
      cells (p<0.005). HLA-DR-positive cells was significantly different between
      stromal (p<0.016) and glandular cells (p<0.044) in each side of endometrioma.
      Finally, HLA-DR-positive percentage cells were significantly more frequent in the
      secretory phase than the proliferative in stromal and glandular cells in both
      groups. CONCLUSION: HLA-DR antigen expression in endometrium and adenomyotic
      tissues. However, HLA-DR expression is distributed preferentially in glandular
      epithelial cells in endometrioma and in the adenomyotic stroma. In both groups
      the HLA-DR expression was significantly higher in the secretory phase than the
      proliferative or glandular and stroma cells. Larger perspective studies are
      needed to establish the expression of HLA antigens in immune reactions which
      occur in adenomyosis and endometriosis.

PMID- 19585137
TI  - Regional metastatic pattern of papillary thyroid carcinoma.
AB  - The objective of the present study was to determine the pattern of lymphatic
      spread in papillary thyroid carcinoma with clinically positive nodes. Between
      1999 and 2008, a total of 48 consecutive patients with clinical evidence of
      cervical lymph node metastasis of papillary thyroid carcinoma underwent 61
      modified radical neck dissections (13 being bilateral) including levels II-VI.
      All neck dissection specimens were separated during surgery into levels and
      analysis was done with respect to the levels of neck. T value of tumor and
      demographic parameters were compared with the number of metastatic nodes with
      univariate analysis. The median number of pathologic nodes in neck dissection
      specimen was 7.0. The predominant site of metastasis was level VI (77%), followed
      by level III (69%), level IV (66%), and level II (46%). Level V showed 34% of
      nodal metastasis. Seven patients had level VII, and five patients had
      parapharyngeal lymph node dissections because of lymphatic involvement at these
      sites. There was no statistically significant correlation between T value, age,
      sex and the number of histologically positive lymph nodes (P = 0.39, P = 0.91 and
      P = 0.84, respectively). It was concluded that the high incidence of metastatic
      disease in levels II through VI supports the recommendation for level II through
      level VI neck dissection in patient with clinically positive neck disease.

PMID- 19585138
TI  - Carbon dioxide laser-assisted phonosurgery for benign glottic lesions.
AB  - The objectives of the study were (1) to evaluate glottic function following
      carbon dioxide laser-assisted phonosurgery of benign laryngeal disease, and (2)
      to assess postoperative glottic morphology and disease recurrence rates, using
      the study design of comparative prospective non-randomized case series of
      patients with benign glottic pathology treated by laser-assisted phonosurgery
      over 10 years. 235 consecutive patients had pre- and postoperative data collected
      by objective laryngeal examination, videostroboscopy recording of vocal fold
      mucosal wave movement, electroacoustic voice analysis (statistical analysis:
      Wilcoxon test) and perceptual voice evaluation. Comparing pre- and postoperative
      functional results demonstrated a statistically significant improvement in all
      spectrographically analysed objective voice parameters (P < 0.001). Postoperative
      morphological analysis confirmed three recurrences of granuloma and one of
      Reinke's oedema. Carbon dioxide laser-assisted voice restoration for benign
      glottic disease is effective.

PMID- 19585139
TI  - Audiovisual assessment of exercise-induced laryngeal obstruction: reliability and
      validity of observations.
AB  - Variable obstruction to airflow at the laryngeal level may cause respiratory
      distress during exercise. The Continuous Laryngoscopy Exercise (CLE)-test enables
      direct visualization of the larynx during ongoing exercise. The aims of this
      study were to establish a scoring system for laryngeal obstruction as visualized
      during the CLE-test as well as to assess reliability and validity of this scoring
      system. Continuous video recording of the larynx was performed in parallel with
      continuous video recording of the upper part of the body, and recording of breath
      sounds in 80 patients and 20 symptom-negative volunteers, running on a treadmill
      to respiratory maximal tolerable distress or exhaustion. Each participant scored
      the degree of symptoms during exercise. The scoring system contains four sub
      scores, each graded from 0 to 3. Two independent laryngologists, blinded to
      clinical data, scored the video recordings of the larynx twice. The proportion of
      inter- and intra-observer agreement (equal scores) for each sub-score through
      these four sessions varied between 70 and 100% (weighted kappa values varied from
      0.49 to 1.00 correspondingly). A positive correlation was found between CLE-test
      sum score and symptom score (rho = 0.75, P < 0.001). There was a significant
      difference in CLE-test sum score between patients (3.34 +/- 1.34) and volunteers
      (0.65 +/- 0.66) (P < 0.001). The single CLE-test sub-score that correlated most
      strongly with symptom score was glottic adduction at maximal effort (rho = 0.75,
      P < 0.001). The presented scoring system is reliable and valid, and we suggest
      that it can be used when laryngeal function during exercise is evaluated.

PMID- 19585140
TI  - The spatial repositioning of adipogenesis genes is correlated with their
      expression status in a porcine mesenchymal stem cell adipogenesis model system.
AB  - Alterations in the nuclear positioning of chromosomes and specific genes during
      differentiation and development have suggested strongly the existence of a
      relationship between non-random organization of the genome and its function. In
      this study, we have examined the genome organization in interphase nuclei during
      adipogenesis, using the pig as a model organism. We hypothesized that changes in
      the gene expression profile and chromatin remodeling which occur during cellular
      differentiation would elicit repositioning of whole chromosomes, moving specific
      genes on them to different regions of the nucleus. We established an in vitro
      adipogenesis differentiation system using mesenchymal stem cells, derived from
      porcine bone marrow. The nuclear position of seven adipogenesis genes (PPARG,
      SREBF1, FABP4, CEBPA, CEBPB, CREB, and GATA2), two control genes (SOX9 and MYL1),
      and six chromosomes carrying these gene loci (SSC4, SSC6, SSC12, SSC13, SSC15,
      and SSC17) was determined. We found that during adipogenesis, using the in vitro
      stem cell model system, in contrast to our original hypothesis, the nuclear
      position of genes involved in adipogenesis was altered radically with the up
      regulation of gene expression correlating with these genes becoming more
      internally located within nuclei. Chromosome territories, containing these genes,
      were also found to alter their nuclear position during the in vitro adipogenesis
      model, with the most dramatic repositioning being SSC4 that moved from the
      nuclear periphery towards the nuclear interior. We found that during in vitro
      adipogenesis chromosome territories decondensed and the genes were found on loops
      and projections of chromatin, away from the main body of the chromosomes. From
      our data, it appears that the temporal repositioning of genes, emanating away
      from chromosomes, during adipogenesis is correlated with gene activity,
      supporting models of the involvement of spatial genome repositioning in
      regulating gene expression and the nuclear interior being an important region of
      the nucleus for transcription.

PMID- 19585141
TI  - Urea promotes TonEBP expression and cellular adaptation in extreme hypertonicity.
AB  - The transcriptional activator TonEBP is a central regulator of osmolality in the
      renal medulla and whole body water homeostasis. In order to understand the
      regulation of TonEBP in the renal medulla, we examined MDCK cells, a kidney
      derived epithelial cell line, under conditions mimicking the renal medulla.
      Moderate changes in ambient tonicity, which was tolerated without prior
      adaptation, displayed lasting effects on TonEBP in bidirectional manner
      stimulated by hypertonicity and inhibited by hypotonicity. TonEBP expression was
      further enhanced by extreme hypertonicity observed in the inner medullae of
      antidiuretic animals. Urea stimulated TonEBP expression and promoted cellular
      proliferation under the conditions of extreme hypertonicity. On the other hand,
      the TonEBP activity was negatively modulated under these conditions presumably to
      temper the highly abundant TonEBP. We conclude that urea is critical to the
      cellular adaptation to extreme hypertonicity and the high level of TonEBP
      expression in the inner medulla.

PMID- 19585142
TI  - Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes
      whose expression is up-regulated in human adipocytes by macrophage-conditioned
      medium.
AB  - White adipose tissue exhibits inflammation as tissue mass expands in obesity,
      involving macrophage infiltration and a direct inflammatory response by
      adipocytes. DNA microarrays and conditioned medium have been used to examine the
      effects of macrophages on global gene expression in human adipocytes. SGBS
      adipocytes, differentiated in culture, were treated with macrophage-conditioned
      medium (U937 cells) for 4 or 24 h; control cells received unconditioned medium.
      Agilent arrays comprising 44,000 probes were used to analyse gene expression.
      Microarray analysis identified 1,088 genes differentially expressed in response
      to the conditioned medium at both 4 and 24 h (754 up-regulated, 334 down
      regulated at 24 h); these included genes associated with inflammation and
      macrophage infiltration. A cluster of matrix metalloproteinase genes were highly
      up-regulated at both time-points, including MMP1, MMP3, MMP9, MMP10, MMP12 and
      MMP19. At 4 and 24 h, MMP1 was the most highly up-regulated gene (>2,400-fold
      increase in mRNA at 24 h). ELISA measurements indicated that substantial
      quantities of MMP1 and MMP3 were released from adipocytes incubated with
      conditioned medium, with little release by control adipocytes. Treatment with
      TNFalpha induced substantial increases in MMP1 (>100-fold) and MMP3 (27-fold)
      mRNA level and MMP1 and MMP3 release in adipocytes, suggesting that this cytokine
      could contribute to the stimulation of MMP expression by macrophages. In
      conclusion, macrophage-secreted factors induce a major inflammatory response in
      human adipocytes, with expression of MMP family members being strongly up
      regulated. The induction of MMP1 and other MMPs suggests that macrophages
      stimulate tissue remodelling during adipose tissue expansion in obesity.

PMID- 19585145
TI  - Is there a structural limit to 'branch' recursively between more than two tasks?
AB  - The term 'branching' refers to processes needed for successful reuptake of a task
      after interruption by another task. Based on a model of human prefrontal
      cognitive architecture, it has been postulated that people cannot branch
      recursively between more than two tasks due to a capacity limit built into the
      cognitive architecture (Koechlin and Hyafil in Science 318:594-598, 2007). As an
      alternative to a structural limit for recursive branching between more than two
      tasks we put forward the hypothesis that working memory capacity is the limiting
      factor in recursive branching. We tested this hypothesis by independently varying
      working memory load and number of recursive branching steps. Successful branching
      between up to four tasks was observed, as long as working memory load was kept
      low. Our data, thus, do not support the proposition of a structural limit to
      recursive branching beyond two tasks. Instead, they suggest that working memory
      capacity limit is the most important factor that limits the capacity for
      branching. We further observed that the requirement to retain task sets and task
      contents additively contributed to the difficulty of recursive branching. In a
      broader context, our data thus support working memory models that conceptualize
      working memory and executive functions not as separate modules, but as tightly
      interactive processes.

PMID- 19585144
TI  - Identification and characterization of 27 conserved microRNAs in citrus.
AB  - MicroRNAs (miRNAs) are a class of non-protein-coding small RNAs. Considering the
      conservation of many miRNA genes in different plant genomes, the identification
      of miRNAs from non-model organisms is both practicable and instrumental in
      addressing miRNA-guided gene regulation. Citrus is an important staple fruit
      tree, and publicly available expressed sequence tag (EST) database for citrus are
      increasing. However, until now, little has been known about miRNA in citrus. In
      this study, 27 known miRNAs from Arabidopsis were searched against citrus EST
      databases for miRNA precursors, of which 13 searched precursor sequences could
      form fold-back structures similar with those of Arabidopsis. The ubiquitous
      expression of those 13 citrus microRNAs and other 13 potential citrus miRNAs
      could be detected in citrus leaf, young shoot, flower, fruit and root by northern
      blotting, and some of them showed differential expression in different tissues.
      Based on the fact that miRNAs exhibit perfect or nearly perfect complementarity
      with their target sequences, a total of 41 potential targets were identified for
      15 citrus miRNAs. The majority of the targets are transcription factors that play
      important roles in citrus development, including leaf, shoot, and root
      development. Additionally, some other target genes appear to play roles in
      diverse physiological processes. Four target genes have been experimentally
      verified by detection of the miRNA-mediated mRNA cleavage in Poncirus trifoliate.
      Overall, this study in the identification and characterization of miRNAs in
      citrus can initiate further study on citrus miRNA regulation mechanisms, and it
      can help us to know more about the important roles of miRNAs in citrus.

PMID- 19585143
TI  - Conserved microRNAs and their targets in model grass species Brachypodium
      distachyon.
AB  - MicroRNAs are small, non-protein-coding RNAs playing regulatory functions in many
      organisms. Using computational approaches 26 new Brachypodium distachyon miRNAs
      belonging to 19 miRNA families were identified in expressed sequence tags (EST)
      and genomic survey sequence databases. EST revealed that predicted miRNAs are
      expressed in B. distachyon. Detailed nucleotide analyses showed that pre-miRNAs
      in B. distachyon are in the range of 63-180 nucleotides. Mature miRNAs located in
      the different positions of precursor RNAs are varied from 19 to 24 nucleotides in
      length. Quantifying RNAs using realtime PCR (qRT-PCR) analyses validated
      expression level differences of selected B. distachyon miRNAs. In this study, we
      detected that the expression level of some of the predicted miRNAs are distinct
      and some of them are similar in the leaf tissues. In addition, using these miRNAs
      as queries 27 potential target mRNAs were predicted in B. distachyon NCBI EST
      database and 246 target mRNA were predicted in NCBI protein-coding nucleotide
      (mRNA) database of all plant species. The majority of the target mRNAs encode
      transcription factors regulating plant development, morphology and flowering
      time. Other newly identified miRNAs target the mRNAs involving metabolic
      processes, signal transduction and stress response.

PMID- 19585146
TI  - Bleeding complications after ritual circumcision: about six children.
AB  - Circumcision is the most common surgical procedure in boys. Even if the procedure
      is frequent, circumcision can have tragic complications. We report the cases of
      six children, seen over 1 year at the emergency department for bleeding
      complication or mutilation after ritual home circumcision. To avoid such
      complications, it is recommended that circumcision should be performed by doctors
      trained in this procedure. Parents have to be cautioned about the risks of
      possible complications after this procedure.

PMID- 19585147
TI  - Detection of low-abundant novel transcripts in mouse hematopoietic stem cells.
AB  - Gene expression profiles of hematopoietic stem cells (HSCs) provide clues for
      understanding molecular mechanisms of HSC behavior, including self-renewal and
      differentiation. We took advantage of serial analysis of gene expression (SAGE)
      to identify medium- and low-abundant transcripts expressed in HSCs/hematopoietic
      progenitor cells (HPCs). Among a total of 31,380 unique transcripts, 17,326 (55%)
      correspond to known genes and, 14,054 (45%) are low-copy transcripts that have no
      matches to currently known genes. Among the former class, 3,899 (23%) were
      alternatively spliced transcripts and 3,754 (22%) represent anti-sense
      transcripts from known genes. Mapping of the SAGE tags to the mouse genome showed
      that differences in gene expression exist among chromosomes. In addition,
      comparison of the HSCs/HPCs SAGE data to that of myeloid progenitor cells
      revealed that massive genetic reprogramming occurs in hematopoietic cell
      differentiation. Our results demonstrate a previously unrecognized complexity of
      gene expression in HSCs/HPCs, and indicate the need for further efforts to fully
      identify and characterize the transcripts expressed in this cell type.

PMID- 19585148
TI  - Evolution of Tom, 297, 17.6 and rover retrotransposons in Drosophilidae species.
AB  - LTR retrotransposons are the most abundant transposable elements in Drosophila
      and are believed to have contributed significantly to genome evolution. Different
      reports have shown that many LTR retrotransposon families in Drosophila
      melanogaster emerged from recent evolutionary episodes of transpositional
      activity. To contribute to the knowledge of the evolutionary history of
      Drosophila LTR retrotransposons and the mechanisms that control their abundance,
      distribution and diversity, we conducted analyses of four related families of LTR
      retrotransposons, 297, 17.6, rover and Tom. Our results show that these elements
      seem to be restricted to species from the D. melanogaster group, except for 17.6,
      which is also present in D. virilis and D. mojavensis. Genetic divergences and
      phylogenetic analyses of a 1-kb fragment region of the pol gene illustrate that
      the evolutionary dynamics of Tom, 297, 17.6 and rover retrotransposons are
      similar in several aspects, such as low codon bias, the action of purifying
      selection and phylogenies that are incongruent with those of the host species. We
      found an extremely complex association among the retrotransposon sequences,
      indicating that different processes shaped the evolutionary history of these
      elements, and we detected a very high number of possible horizontal transfer
      events, corroborating the importance of lateral transmission in the evolution and
      maintenance of LTR retrotransposons.

PMID- 19585150
TI  - Plasticity and regulatory mechanisms of Hox gene expression in mouse neural crest
      cells.
AB  - In amniotes, the developmental potentials of neural crest cells differ between
      the cranium and the trunk. These differences may be attributable to the different
      expression patterns of Hox genes between cranial and trunk neural crest cells.
      However, little is known about the factors that control Hox genes expression in
      neural crest cells. The present data demonstrate that retinoic acid (RA)
      treatment and the activation of Wnt signaling induce Hoxa2 and Hoxd9 expression,
      respectively, in mouse mesencephalic neural crest cells, which never express Hox
      genes in vivo. Furthermore, Wnt signaling suppresses the induction of Hoxa2. We
      also demonstrate that these factors participate in the maintenance of Hoxa2 and
      Hoxd9 expression in mouse trunk neural crest cells. Our results suggest that RA
      and Wnt signaling function as environmental factors that regulate the expression
      of Hoxa2 and Hoxd9 in mouse neural crest cells.

PMID- 19585151
TI  - Ultrastructure of neuroglial contacts in crayfish stretch receptor.
AB  - In order to explore neuroglial relationships in a simple nervous system, we have
      studied the ultrastructure of the crayfish stretch receptor, which consists of
      only two mechanoreceptor neurons enwrapped by glial cells. The glial envelope
      comprises 10-30 glial layers separated by collagen sheets. The intercellular
      space between the neuronal and glial membranes is generally less than 10-15 nm in
      width. This facilitates diffusion between neurons and glia but restricts neuron
      communication with the environment. Microtubule bundles passing from the
      dendrites to the axon through the neuron body limit vesicular transport between
      the perikaryon and the neuronal membrane. Numerous invaginations into the neuron
      cytoplasm strengthen glia binding to the neuron and shorten the diffusion pathway
      between them. Double-membrane vesicles containing fragments of glial, but not
      neuronal cytoplasm, represent the captured tips of invaginations. Specific
      triads, viz., "flat submembrane cisterns - vesicles - mitochondria", are
      presumably involved in the formation of the invaginations and double-membrane
      vesicles and in neuroglial exchange. The tubular lattice in the glial cytoplasm
      might transfer ions and metabolites between the glial layers. The integrity of
      the neuronal and glial membranes is impaired in some places. However, free
      neuroglial passage might be prevented or limited by the dense diffuse material
      accumulated in these regions. Thus, neuroglial exchange with cellular components
      might be mediated by transmembrane diffusion, especially in the invaginations and
      submembrane cisterns, by the formation of double-walled vesicles in which large
      glial masses are captured and by transfer through tubular lattices.

PMID- 19585149
TI  - Genetic risk factors for melanoma.
AB  - The genetic basis of melanoma is complex and has both inherited and acquired
      components. Different genomic approaches have been used to identify a number of
      inherited risk factors, which can be stratified by penetrance and prevalence.
      Rare high-penetrance factors are expressed in familial clustering of melanoma and
      include mutations in CDKN2A (encoding p16(INK4a) and p14(ARF)) and CDK4. These
      genes are involved in cell-cycle arrest and melanocyte senescence and are nearly
      invariably targeted by somatic mutations during melanoma progression. Low
      penetrance factors are common in the general population and include single
      nucleotide polymorphisms in or near MC1R, ASIP, TYR and TYRP1. These genes are
      major determinants of hair and skin pigmentation, but their role in melanoma
      development remains unclear. This review describes the efforts that have led to
      the current understanding of melanoma susceptibility as the result of complex
      gene-gene and gene-environment interactions. Despite the significant advances,
      the majority of familial cases remain unaccounted for.

PMID- 19585152
TI  - Inter-population differences in the tolerance of a marsupial folivore to plant
      secondary metabolites.
AB  - Plant secondary metabolites (PSMs) strongly influence diet selection by mammalian
      herbivores. Concentrations of PSMs vary within and among plant species, and
      across landscapes. Therefore, local adaptations may cause different populations
      of herbivores to differ in their ability to tolerate PSMs. Here, we tested the
      food intake responses of three populations of a marsupial folivore, the common
      brushtail possum (Trichosurus vulpecula Kerr), from different latitudes and
      habitat types, to four types of PSMs. We found clear variation in the responses
      of northern and southern Australian possums to PSMs. Brushtail possums from
      southern Australia showed marked decreases in food intake in response to all four
      PSMs, while the two populations from northern Australia were not as sensitive and
      their responses did not differ from one another. These results were unexpected,
      based on our understanding of the experiences of these populations with PSMs in
      the wild. Our results suggest that geographically separated populations of
      possums may have evolved differing abilities to cope with PSMs, as a result of
      local adaptation to their natural environments. Our results provide the basis for
      future studies to investigate the mechanisms by which populations of mammalian
      species differ in their ability to tolerate PSMs.

PMID- 19585154
TI  - Foliar water uptake: a common water acquisition strategy for plants of the
      redwood forest.
AB  - Evaluations of plant water use in ecosystems around the world reveal a shared
      capacity by many different species to absorb rain, dew, or fog water directly
      into their leaves or plant crowns. This mode of water uptake provides an
      important water subsidy that relieves foliar water stress. Our study provides the
      first comparative evaluation of foliar uptake capacity among the dominant plant
      taxa from the coast redwood ecosystem of California where crown-wetting events by
      summertime fog frequently occur during an otherwise drought-prone season.
      Previous research demonstrated that the dominant overstory tree species, Sequoia
      sempervirens, takes up fog water by both its roots (via drip from the crown to
      the soil) and directly through its leaf surfaces. The present study adds to these
      early findings and shows that 80% of the dominant species from the redwood forest
      exhibit this foliar uptake water acquisition strategy. The plants studied include
      canopy trees, understory ferns, and shrubs. Our results also show that foliar
      uptake provides direct hydration to leaves, increasing leaf water content by 2
      11%. In addition, 60% of redwood forest species investigated demonstrate
      nocturnal stomatal conductance to water vapor. Such findings indicate that even
      species unable to absorb water directly into their foliage may still receive
      indirect benefits from nocturnal leaf wetting through suppressed transpiration.
      For these species, leaf-wetting events enhance the efficacy of nighttime re
      equilibration with available soil water and therefore also increase pre-dawn leaf
      water potentials.

PMID- 19585153
TI  - Evidence that phylogenetically novel non-indigenous plants experience less
      herbivory.
AB  - The degree to which biotic interactions influence invasion by non-indigenous
      species may be partly explained by the evolutionary relationship of these
      invaders with natives. Darwin's naturalization hypothesis controversially
      proposes that non-native plants are more likely to invade if they lack close
      relatives in their new range. A possible mechanism for this pattern is that
      exotics that are more closely related to natives are more likely to share their
      herbivores, and thus will suffer more damage than phylogenetically isolated
      species. We tested this prediction using exotic plants in Ontario, Canada. We
      measured herbivore damage to 32 species of exotic plants in a common garden
      experiment, and 52 in natural populations. We estimated their phylogenetic
      distances from locally occurring natives in three ways: as mean distance (age) to
      all native plants, mean distance to native members of the same family, and
      distance to the closest native species. In the common garden, the proportion of
      leaves damaged and the average proportion of leaf area damaged declined with mean
      phylogenetic distance to native family relatives by late summer. Distance to
      native confamilials was a better predictor of damage than distance to the closest
      native species, while mean distance to the entire native plant community failed
      to predict damage. No significant patterns were detected for plants in natural
      populations, likely because uncontrolled site-to-site variation concealed these
      phylogenetic trends. To the extent that herbivory has negative demographic
      impacts, these results suggest that exotics that are more phylogenetically
      isolated from native confamilials should be more invasive; conversely, native
      communities should be more resistant to invasion if they harbor close familial
      relatives of potential invaders. However, the large scatter in this relationship
      suggests that these often are likely to be weak effects; as a result, these
      effects often may be difficult to detect in uncontrolled surveys of natural
      populations.

PMID- 19585155
TI  - [Psychosocial factors in chronic low back pain in orthopaedic inpatient
      rehabilitation. An analysis using the axes of the Mainz Pain Staging System].
AB  - BACKGROUND: The aim of this study was to investigate the criterion validity of
      the Mainz Pain Staging System (MPSS), considering the four axes of the MPSS
      separately. METHODS AND DESIGN: Psychological and pain-related impairments were
      analysed depending on the stage of axis (I, II, III) for each single axis of the
      MPSS in a consecutive sample of 280 patients with chronic low back pain in
      orthopaedic inpatient rehabilitation. In addition, the distribution of frequency
      of clinically significant symptoms in depression, anxiety and somatisation were
      examined depending on the stage of axis. RESULTS: For all axes, an increasing
      stage was associated with greater psychological and pain-related impairments.
      Particularly patients assigned to stage III on axis 1 (temporal aspects) and 2
      (spatial aspects) and patients assigned to stage II on axis 3 (drug intake) and 4
      (utilisation of the health care system) showed enhanced psychosocial impairments
      and more frequently had clinically relevant symptoms in psychological variables.
      CONCLUSION: Findings confirm the criterion validity of the MPSS for chronic low
      back pain. In addition, results support the significance of psychosocial factors
      for the further development of chronicity.

PMID- 19585156
TI  - [Successful treatment of treatment-resistant opioid-induced constipation in a
      patient with incomplete paraplegia with methylnaltrexone].
AB  - We observed a patient with incomplete, cervical paraplegia and opioid-induced
      constipation who developed a resistance to laxatives after 15 years of treatment.
      The constipation-induced reduction in the patient's quality of life was improved
      using 12 mg methylnaltrexone, a peripheral mu-opioid receptor antagonist,
      administered subcutaneously twice a week.

PMID- 19585157
TI  - [Specialized outpatient palliative treatment by the Bochum Medical Service for
      Palliative Treatment].
AB  - Most people would like to spend the end of their life at home in their familiar
      surroundings. Is it possible to look after and care for people at home if the
      work of doctors, carers and hospices is coordinated and comprehensive? MATERIAL
      AND METHODS: After receiving approval from the Ethics Committee of the Ruhr
      University Medical Faculty, the data of patients at the Bochum Medical Service
      for Palliative Treatment were anonymized and statistically evaluated. RESULTS:
      Complete data from 104 patients were evaluated. On average, the patients were
      69.8 years old, and 91% were suffering from malignancies. In 95% of the patients,
      the main symptom was fatigue, followed by pain (87%) of a mean score of NRS 5.5.
      Of those patients who were treated and looked after until the end of their lives,
      only 15.8% died in hospital and 73% of them on the palliative care ward.
      CONCLUSION: Our results indicate that by introducing a specialized structure for
      outpatient palliative care, including a specialized 24-h palliative medical
      service, an improvement in total care for patients at the end of their lives can
      be achieved.

PMID- 19585158
TI  - Image fusion for preoperative evaluation of vertebral artery in a patient with
      atlantoaxial vertical subluxation and chronic renal failure.
AB  - For preoperative evaluation of the vertebral artery (VA) at the craniovertebral
      junction, 3-dimensional (3-D) computed tomography (CT) angiography can
      simultaneously and precisely depict the location of the VA and the
      circumferential osseous tissues. However, this procedure has the risk of contrast
      induced nephropathy, especially when patients have pre-existing renal impairment.
      We report the case of a 73-year-old woman with rheumatoid arthritis and
      concomitant chronic renal failure in whom severe myelopathy developed due to
      atlantoaxial vertical subluxation and subaxial subluxation. We planned to perform
      C1 laminectomy and C3-C7 laminoplasty, but to avoid the risk of intraoperative VA
      injury, we applied a fusion image technique of 3-D magnetic resonance (MR)
      angiography and co-registered 3-D CT that allowed for virtual assessment
      preoperatively of the VA courses, instead of 3-D CT angiography. Through the 3-D
      hybrid MR angiography-CT images, we could predict, in detail, the VA courses and
      the surrounding bony structures. At surgery, we found that the locations of the
      VAs were identical to that predicted on the preoperative image fusion analysis.
      We conclude that our image fusion techniques possess accurate diagnostic value
      for detecting arterial course, and could be applicable for patients in whom
      administration of contrast media should be avoided due to specific conditions,
      such as drug allergy and chronic renal failure.

PMID- 19585159
TI  - Local and global subaxial cervical spine biomechanics after single-level fusion
      or cervical arthroplasty.
AB  - An experimental in vitro biomechanical study was conducted on human cadaveric
      spines to evaluate the motion segment (C4-C5) and global subaxial cervical spine
      motion after placement of a cervical arthroplasty device (Altia TDI,Amedica, Salt
      Lake City, UT) as compared to both the intact spine and a single-level fusion.
      Six specimens (C2-C7) were tested in flexion/extension, lateral bending, and
      axial rotation under a +/- 1.5 Nm moment with a 100 N axial follower load.
      Following the intact spine was tested; the cervical arthroplasty device was
      implanted at C4-C5 and tested. Then, a fusion using lateral mass fixation and an
      anterior plate was simulated and tested. Stiffness and range of motion (ROM) data
      were calculated. The ROM of the C4-C5 motion segment with the arthroplasty device
      was similar to that of the intact spine in flexion/extension and slightly less in
      lateral bending and rotation, while the fusion construct allowed significantly
      less motion in all directions. The fusion construct caused broader effects of
      increasing motion in the remaining segments of the subaxial cervical spine,
      whereas the TDI did not alter the adjacent and remote motion segments. The fusion
      construct was also far stiffer in all motion planes than the intact motion
      segment and the TDI, while the artificial disc treated level was slightly stiffer
      than the intact segment. The Altia TDI allows for a magnitude of motion similar
      to that of the intact spine at the treated and adjacent levels in the in vitro
      setting.

PMID- 19585160
TI  - Difference in redox behaviors between copper-binding octarepeat and nonoctarepeat
      sites in prion protein.
AB  - We studied the redox behavior of copper-binding sites in prion protein (PrP) to
      clarify copper's role in the pathological mechanism underlying prion diseases. We
      investigated the coordination structures, binding affinities, and redox
      potentials of copper-binding peptide fragments derived from the N-terminal domain
      of PrP by density functional theory calculations. We used four models for copper
      binding moieties in PrP(60-96): two were derived from the PHGGGWGQ octapeptide
      repeat region of PrP(60-91), and the others were tripeptide Gly-Thr-His fragments
      derived from the copper-binding nonoctarepeat site around His96. We found that
      such PrP-derived copper-binding complexes exhibit conformationally dependent
      redox behavior; for example, the copper-binding complex derived from the
      octarepeat region tends to possess high reduction potential for the Cu(II)/Cu(I)
      couple, exceeding 0 V versus the standard hydrogen electrode, whereas the copper
      binding nonoctarepeat model around His96 tends to possess high oxidation
      potential for the Cu(II)/Cu(III) couple and stabilize the higher-valent Cu(III)
      state. It is possible that such distinct redox activities of a copper-binding PrP
      are involved in the mechanism underlying prion diseases.

PMID- 19585161
TI  - Computational modeling of the dizinc-ferroxidase complex of human H ferritin:
      direct comparison of the density functional theory calculated and experimental
      structures.
AB  - Density functional theory optimizations of structures of dizinc(II) complexes
      with a six-residue model of the ferroxidase center of human H ferritin have been
      performed and the results compared with the crystallographically determined
      structure of the complex as presented in Protein Data Bank file 2CEI. The model
      employs the full structures of Glu27, Glu62, His65, Glu107, Gln141, and Ala144,
      and the structural effect of Tyr34 is also examined. The mean absolute deviation
      from experiment of atomic positions in the best calculated structures is less
      than 0.3 A. The experimental structure is reproduced well enough to determine the
      coordination environment of the metal ions. Each zinc(II) center is
      pentacoordinate with a single water ligand, and the two centers are bridged by a
      hydroxide ion. Ala144 interacts weakly and repulsively with the rest of the
      complex. Tyr34 displays a weak attraction through a hydrogen bond to Glu107 that
      affects the orientation of that group.

PMID- 19585162
TI  - A review of studies mapping (or cross walking) non-preference based measures of
      health to generic preference-based measures.
AB  - Clinical studies use a wide variety of health status measures to measure health
      related quality of life, many of which cannot be used in cost-effectiveness
      analysis using cost per quality adjusted life year (QALY). Mapping is one
      solution that is gaining popularity as it enables health state utility values to
      be predicted for use in cost per QALY analysis when no preference-based measure
      has been included in the study. This paper presents a systematic review of
      current practice in mapping between non-preference based measures and generic
      preference-based measures, addressing feasibility and validity, circumstances
      under which it should be considered and lessons for future mapping studies. This
      review found 30 studies reporting 119 different models. Performance of the
      mappings functions in terms of goodness-of-fit and prediction was variable and
      unable to be generalised across instruments. Where generic measures are not
      regarded as appropriate for a condition, mapping does not solve this problem.
      Most testing in the literature occurs at the individual level yet the main
      purpose of these functions is to predict mean values for subgroups of patients,
      hence more testing is required.

PMID- 19585163
TI  - A comparison of polysomnographic variables between obese adolescents with
      polycystic ovarian syndrome and healthy, normal-weight and obese adolescents.
AB  - PURPOSE: The purpose of this study was to determine the differences in
      polysomnographic variables between obese adolescents with polycystic ovarian
      syndrome (PCOS) and healthy, normal-weight and obese controls, as the prevalence
      of obstructive sleep apnea syndrome (OSAS) is increased in adults with PCOS.
      METHODS: Twenty-two obese adolescents with PCOS (mean age 15.2 +/- 1.3 years,
      mean BMI 31.7 +/- 6.2 kg/m(2)), 18 healthy, normal-weight adolescents (mean age
      15.0 +/- 0.9 years, mean BMI 20.6 +/- 2.3 kg/m(2)), and 11 healthy, obese
      adolescents (mean age 15.0 +/- 1.0 years, mean BMI 34.8 +/- 8.7 kg/m(2))
      underwent polysomnography to compare mean transcutaneous arterial oxygen
      saturation (Sat O(2)), apnea index (AI), hypopnea index (HI), apnea-hypopnea
      index (AHI), the absolute number of obstructive apneas (NOA), percentage sleep
      stages 3 and 4 of non-REM sleep (stages 3 and 4), percentage of REM sleep (%REM),
      sleep-onset latency, and sleep efficiency. RESULTS: We found no differences
      between the three groups concerning Sat O(2), AI, HI, AHI, NOA, and stages 3 and
      4. The girls with PCOS differed from normal-weight and obese controls regarding
      sleep-onset latency and sleep efficiency and from the normal-weight controls
      regarding %REM. CONCLUSIONS: OSAS does not seem to be more prevalent in
      adolescents with PCOS. Concerning the respiratory variables, adolescents with
      PCOS do not seem to differ from healthy controls; however, there seem to be
      differences concerning sleep architecture.

PMID- 19585164
TI  - Omega-3 fatty acids regulate gene expression levels differently in subjects
      carrying the PPARalpha L162V polymorphism.
AB  - Omega-3 fatty acids (FAs) are natural ligands of the peroxisome proliferator
      activated receptor-alpha (PPARalpha), a nuclear receptor that modulates
      expression levels of genes involved in lipid metabolism. The L162V polymorphism
      of the PPARalpha gene is associated with a deteriorated metabolic profile. We
      postulate that subjects carrying the PPARalpha-V162 allele exhibit differences in
      the expression of PPARalpha and its target genes after incubation with omega-3
      FAs compared with L162 homozygotes. Peripheral blood monocytes from six men
      carrying the PPARalpha-V162 allele paired for age and for body mass index with
      six L162 homozygotes were differentiated into macrophages and activated with
      eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or mixtures of EPA:DHA.
      Data demonstrates that gene expression levels of PPARalpha and apolipoprotein AI
      (APOA1) were significantly lower for carriers of the PPARalpha-V162 allele
      compared to L162 homozygotes after the addition of DHA and a mixture of EPA:DHA.
      Additionally, lipoprotein lipase (LPL) gene expression displayed a tendency to be
      lower in the PPARalpha L162V polymorphism subgroup after the addition of a
      mixture of EPA:DHA. Consequently, individuals carrying the PPARalpha-V162 allele
      may demonstrate inferior improvements in their lipid profile due to alterations
      in gene expression rates in response to omega-3 FA supplementation.

PMID- 19585165
TI  - Two concomitant arrhythmias in a transplanted heart.

PMID- 19585167
TI  - Sympathetic skin response in primary Raynaud's phenomenon.
AB  - OBJECTIVES: The pathogenetic hypotheses of Raynaud's phenomenon include increased
      activation of sympathetic noradrenergic nerves controlling muscle tone of digit
      arteriolar walls. Because acral sympathetic fibres contain vasoactive adrenergic
      and cholinergic fibres for sweat glands, we tested cholinergic sympathetic fibre
      function in primary Raynaud's phenomenon (PRP) patients by sympathetic skin
      response (SSR). METHODS: Twenty-six consecutive patients (19 women, 7 men, mean
      age 37.8 years) with PRP were enroled prospectively. SSR was obtained by random
      electrical stimulation of the left ulnar nerve at the wrist recording from the
      palm (PSSR), third (M3SSR) and fifth fingers (U5SSR) on the right side. For each
      subject latency of shortest response, area of largest response and grand mean
      latencies and areas of 12 consecutive responses were calculated. The differences
      between patients and a control group (15 women, 6 men, mean age 38.9 years) were
      calculated. SSR habituation was also compared between patients and controls.
      RESULTS: PSSRs were recorded in all patients and no difference in any PSSR
      parameter was found between patients and controls. U5SSRs and M3SSRs were absent
      in two patients. Grand mean area and mean of largest M3SSRs and U5SSRs were
      significantly lower in patients than in controls. Grand mean latency and mean of
      shortest M3SSRs and U5SSRs were significantly slower in patients than in
      controls. M3 and U5SSRs habituated less in patients than in controls.
      INTERPRETATION: Dysregulation of cholinergic sympathetic fibres innervating the
      fingers was found in PRP. Abnormal peripheral mechanisms may be the cause. Since
      SSR habituation was also not normal, even central mechanisms may be implicated.

PMID- 19585166
TI  - HLA class II alleles in patients with multiple sclerosis  in the Biscay province
      (Basque Country, Spain).
AB  - Genetic susceptibility to multiple sclerosis (MS) is associated with genes of the
      major histocompatibility complex, particularly with the HLA DRB1*1501-DQA1*0102
      DQB1*0602 haplotype in Caucasians. To investigate the association of DRB1, DQA1
      and DQB1 alleles and haplotypes with MS in Biscay, Basque Country, northern
      Spain, we examined 197 patients and 200 regionally matched controls. High
      resolution HLA class II typing was performed by polymerase chain reaction
      followed by sequence-specific oligonucleotide probe hybridization. Several
      alleles were overrepresented in MS patients compared with those of controls:
      DRB1*0402, DRB1*1303, DRB1*1501, DQA1*0102, DQB1*0301, and DQB1*0602. DQB1*0602
      was the only potentially predisposing allele for MS that withstood Bonferroni
      correction and maintained the association in a logistic regression model. On the
      other hand, several alleles showed lower frequencies in the MS group: DRB1*0101,
      DQA1*0101, DQB1*0303, and DQB1*0501, but only DRB1*0101 and DQB1*0303 maintained
      a negative association with the disease in the regression analysis. Three
      haplotypes were identified as potentially predisposing for MS in our population:
      DRB1*1501-DQA1*0102-DQB1*0602, DRB1*0402-DQA1*0301-DQB1*0302, and HLA-DRB1*013
      DQA1*05-DQB1*0301. Additionally, three haplotypes associated with a lower risk
      for MS were identified, exhibiting DRB1*0101-DQA1*0101-DQB1*0501 the strongest
      negative association with MS [12% in controls vs. 3.8% in MS, Pc = 0.00047, OR =
      0.290 (95% CI = 0.160-0.528)], and suggesting, therefore, a putative protective
      role for this haplotype in the population under study.

PMID- 19585168
TI  - Differential gene expression during smoltification of Atlantic salmon (Salmo
      salar L.): a first large-scale microarray study.
AB  - The life cycle of the Atlantic salmon (Salmo salar) involves a period of 1 to 3
      years in freshwater followed by migration to the sea where the salmon undergoes
      rapid growth. In preparation for the marine environment, while still in
      freshwater, the salmon undergo a transformation from a freshwater dwelling parr
      to a saltwater adapted smolt, a process known as smoltification. The Atlantic
      salmon Transcriptome Analysis of Important Traits of Salmon/Salmon Genome Project
      (TRAITS/SGP) cDNA microarray was used to investigate how gene expression alters
      during smoltification. Genes differentially expressed during smoltification were
      identified by comparing gene expression profiles in smolt brain, gill, and kidney
      tissue samples with those of parr. Of the three tissues investigated, the number
      of differentially expressed genes was the greatest in gill. Many of the
      differentially expressed genes could be assigned to one of four main categories:
      growth, metabolism, oxygen transport, and osmoregulation. Quantitative polymerase
      chain reaction successfully confirmed the differential expression of seven of the
      upregulated genes. The TRAITS/SGP cDNA microarray was used to successfully
      demonstrate for the first time how gene expression mediates smoltification in the
      Atlantic salmon. Changes in gene expression observed in this study reflected the
      physiological and biochemical changes recorded by previous studies describing the
      parr-smolt transformation. This study significantly increases our knowledge of
      smoltification and will benefit future studies in this area of research.

PMID- 19585169
TI  - Farming sponges to supply bioactive metabolites and bath sponges: a review.
AB  - Sponges have been experimentally farmed for over 100 years, with early attempts
      done in the sea to supply "bath sponges". During the last 20 years, sponges have
      also been experimentally cultured both in the sea and in tanks on land for their
      biologically active metabolites, some of which have pharmaceutical potential. Sea
      based farming studies have focused on developing good farming structures and
      identifying the optimal environmental conditions that promote production of bath
      sponges or bioactive metabolites. The ideal farming structure will vary between
      species and regions, but will generally involve threading sponges on rope or
      placing them inside mesh. For land-based sponge culture, most research has
      focused on determining the feeding requirements that promote growth. Many sea-
      and land-based studies have shown that sponges grow quickly, often doubling in
      size every few months. Other favorable results and interesting developments
      include partially harvesting farmed sponges to increase biomass yields, seeding
      sexually reproduced larvae on farming structures, using sponge farms as large
      biofilters to control microbial populations, and manipulating culture conditions
      to promote metabolite biosynthesis. Even though some results are promising, land
      based culture needs further research and is not likely to be commercially
      feasible in the near future. Sea-based culture still holds great promise, with
      several small-scale farming operations producing bath sponges or metabolites. The
      greatest potential for commercial bath sponge culture is probably for
      underdeveloped coastal communities, where it can provide an alternative and
      environmentally friendly source of income.

PMID- 19585171
TI  - Web-based training method for interpretation of dental images.

PMID- 19585170
TI  - Construction and characterization of a bacterial artificial chromosome (BAC)
      library of Pacific white shrimp, Litopenaeus vannamei.
AB  - The pacific white shrimp (Litopenaeus vannamei) is one of the most economically
      important marine aquaculture species in the world. To facilitate gene cloning and
      characterization, genome analysis, physical mapping, and molecular selection
      breeding of marine shrimp, we have developed the techniques to isolate high
      quality megabase-sized DNA from hemocyte nuclear DNA of female shrimp and
      constructed a bacterial artificial chromosome (BAC) genomic library for the
      species. The library was constructed in the Hind III site of the vector pECBAC1,
      consisting of 101,760 clones arrayed in 265 384-well microtiter plates, with an
      average insert size of 101 kb, and covering the genome approximately fivefold. To
      characterize the library, 92,160 clones were spotted onto high-density nylon
      filters for hybridization screening. A set of 18 pairs of overgo probes designed
      from eight cDNA sequences of L. vannamei genes were used in hybridization
      screening, and 35 positive clones were identified. These results suggest that the
      shrimp BAC libraries will provide a useful resource for screening of genomic
      regions of interest candidate genes, gene families, or large-sized synthetic DNA
      region and promote future works on comparative genomics, physical mapping, and
      large-scale genome sequencing in the species.

PMID- 19585172
TI  - Patterns of care with a positive sentinel node: echoes of an opportunity missed.

PMID- 19585173
TI  - Complete response of an initially non-surgical adenocarcinoma of the duodenum to
      chemotherapy with the FOLFOX 4 regimen.
AB  - INTRODUCTION: The incidence of adenocarcinoma of the small bowel is very low in
      comparison with that of colorectal cancer. Radical surgery is the only curative
      treatment, and results with chemotherapy and radiotherapy are disappointing. No
      standard chemotherapy is defined for non-surgical adenocarcinoma of the small
      bowel. In France, it is usually treated with the same chemotherapy regimens as
      used for colorectal cancer. CASE REPORT: We report here the case of a young
      patient with an initially non-surgical adenocarcinoma of the duodenum treated in
      a palliative setting with the FOLFOX 4 chemotherapy regimen. After 4 months of
      treatment, CT scan showed no residual tumor and the patient was well. A
      multidisciplinary committee decided that a second surgical investigation was
      necessary, and a duodenal resection was performed, with no residual tumor in the
      final specimen. After 27 months of follow-up the patient was well and without
      recurrence. CONCLUSION: The FOLFOX 4 regimen seems to be efficacious for some
      small-bowel adenocarcinomas and can be expected to lead to downstaging. If the
      outcome of a few months of chemotherapy is favorable, it is appropriate for a
      multidisciplinary expert committee to consider further surgery. This case
      underscores the value of multidisciplinary expert committees in scrutinizing
      therapeutic decisions in rare and difficult cases.

PMID- 19585174
TI  - Forkhead transcription factor Foxo1 is essential  for adipocyte differentiation.
AB  - We analyzed the physiological role of forkhead box class O 1 (Foxo1) in adipocyte
      differentiation by suppressing Foxo1 mRNAwith siRNA specific for Foxo1.Mouse 3T3
      L1 preadipocytes infected with an adenovirus expressing Foxo1-siRNA showed a
      marked decrease in lipid droplet formation when induced to differentiate into
      adipocytes. Adipocyte differentiation was most severely inhibited by exposing
      cells to Foxo1-siRNA before induction of differentiation. The incorporation of
      fluorescent-labeled glucose and fatty acid was significantly inhibited in cells
      deficient in Foxo1. RTPCR revealed that downregulation of Foxo1 decreased the
      expression of the transcription factors, PPAR-gamma and C/EBP-alpha. By
      comparison, Foxo1-siRNA did not affect the expression of C/EBP-beta or C/EBP
      delta during the early period of adipocyte differentiation. These results
      indicate that Foxo1 plays an essential role in adipocyte differentiation,
      especially at the very early stage of terminal adipocyte differentiation.

PMID- 19585175
TI  - Cross talk between hedgehog and bone morphogenetic proteins occurs during
      cardiomyogenesis in P19 cells.
AB  - Hedgehog (Hh) signaling plays a role in heart morphogenesis and can initiate
      cardiomyogenesis in P19 cells. To determine if Hh signaling is essential for P19
      cell cardiomyogenesis, we determined which Hh factors are expressed and the
      effect of Hh signal transduction inhibitors. Here, we find that the Hh gene
      family and their downstream mediators are expressed during cardiomyogenesis but
      an active Hh signaling pathway is not essential. However, loss of Hh signaling
      resulted in a delay of BMP-4, GATA-4, Gli2, and Meox1 expression during
      cardiomyogenesis. By using Noggin-overexpressing P19 cells, we determined that Hh
      signaling was not active during Noggin-mediated inhibition of cardiomyogenesis.
      Thus, there is cross talk between the Hh and BMP signaling pathways and the Hh
      pathway appears important for timely cardiomyogenesis.

PMID- 19585176
TI  - Some studies on the morphological aspects of buffalo oocytes in relation to the
      ovarian morphology and culture condition.
AB  - The present study was conducted to establish the effects of ovarian morphology on
      oocyte quantity and quality, as well as the effect of preincubated granulosa
      cells (PGCs) on in vitro maturation of buffalo oocytes and steroid hormones
      production. A total of 52 ovarian pairs were grouped into three types: type I
      (with functional corpus luteum), type II (with regressed corpus luteum), and type
      III (without corpus luteum). The number of follicles and oocytes/ovary were
      documented. The follicles were classified into three groups (<2, 2-6, and >6 mm
      O). Oocytes were classified according to their morphology into four grades
      (grades A, B, C, and D), or according to their cumulus compactness into four
      groups (more than three layers, one to three layers of cumulus cells, partial
      remnants of cumulus cells, and no cumulus cells). A PGCs was used to investigate
      their steroidogenic potential on the in vitro maturation. The highest number of
      follicles and oocytes was found in type III than types II and I. Grades A and B
      oocytes were significantly higher (P < 0.01) in number in type III ovaries.
      Oocytes with more than three layers of cumulus cells showed higher maturation
      rate than oocytes with partial remnants or no cumulus cells but with small
      difference from oocytes having one to three layers of cumulus cells. Beside the
      higher maturation rate in compact than denuded oocytes, a significantly higher (P
      < 0.01) rates obtained in compact or denuded oocytes when cultured in vitro with
      PGCs than the corresponding oocytes with no PGCs. These maturation rates
      coincided with higher level (P < 0.05) of estradiol-17ss when compact oocytes
      cultured with or without PGCs than denuded oocytes and higher level (P < 0.05) of
      progesterone after culture with PGCs for both compact and denuded oocytes than
      the corresponding oocytes with no PGCs. In summary, buffalo ovaries with no
      corpus luteum may be suggested for obtaining high number of follicles and good
      oocytes than the others. Oocytes with intact cumulus showed better maturation
      than those with partial or denuded cumulus, although the denuded oocytes improved
      their meiotic competence to a less or greater extent when cultured in vitro with
      PGCs.

PMID- 19585178
TI  - Aligning incentives in orthopaedics: opportunities and challenges -- the Case
      Medical Center experience.
AB  - For 30 years, the orthopaedic faculty at Case Western Reserve University worked
      as an independent private corporation within University Hospitals Case Medical
      Center (Hospital). However, by 2002, it became progressively obvious to our
      orthopaedic practice that we needed to modify our business model to better manage
      the healthcare regulatory changes and decreased reimbursement if we were to
      continue to attract and retain the best and brightest orthopaedic surgeons to our
      practice. In 2002, our surgeons created a new entity wholly owned by the parent
      corporation at the Hospital. As part of this transaction, the parties negotiated
      a balanced employment model designed to fully integrate the orthopaedic surgeons
      into the integrated delivery system that included the Hospital. This new faculty
      practice plan adopted a RVU-based compensation model for the physicians, with
      components that created incentives both for clinical practice and for academic
      and administrative service contributions. Over the past 5 years, aligning
      incentives with the Hospital has substantially increased the clinical
      productivity of the surgeons and has also benefited the Hospital and our
      patients. Furthermore, aligned incentives between surgeons and hospitals could be
      of substantial financial benefit to both, as Medicare moves forward with its
      bundled project initiative.

PMID- 19585177
TI  - Preoperative pain catastrophizing predicts pain outcome after knee arthroplasty.
AB  - Psychologic status is associated with poor outcome after knee arthroplasty yet
      little is known about which specific psychologic disorders or pain-related
      beliefs contribute to poor outcome. To enhance the therapeutic effect of a
      psychologic intervention, the specific disorders or pain-related beliefs that
      contributed to poor outcome should be identified. We therefore determined whether
      specific psychologic disorders (ie, depression, generalized anxiety disorder,
      panic disorder) or health-related beliefs (ie, self-efficacy, pain
      catastrophizing, fear of movement) are associated with poor outcome after knee
      arthroplasty. We conducted a cohort study of 140 patients undergoing knee
      arthroplasty at two hospitals. Patients completed a series of psychologic
      measures, provided various sociodemographic data, and were followed for 6 months.
      Patients were dichotomized to groups with either a favorable or a poor outcome
      using WOMAC pain and function scores and evidence-based approaches. After
      adjusting for confounding variables, we found pain catastrophizing was the only
      consistent psychologic predictor of poor WOMAC pain outcome. No psychologic
      predictors were associated consistently with poor WOMAC function outcome. An
      intervention focusing on pain catastrophizing seems to have potential for
      improving pain outcome in patients prone to catastrophizing pain. LEVEL OF
      EVIDENCE: Level I, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19585180
TI  - Eligibility for organ donation: a medico-legal perspective on defining and
      determining death.
AB  - PURPOSE: In the context of post-mortem organ donation, there is an obvious need
      for certainty regarding the legal definition and determination of death, as
      individuals must be legally pronounced dead before organs may be procured for
      donation. Surprisingly then, the legal situation in Canada with regard to the
      definition and determination of death is uncertain. The purpose of this review is
      to provide anesthesiologists and critical care specialists with a medico-legal
      perspective regarding the definition and determination of death (particularly as
      it relates to non-heart-beating donor protocols) and to contribute to ongoing
      improvement in policies, protocols, and practices in this area. PRINCIPAL
      FINDINGS: The status quo with regard to the current legal definition of death is
      presented as well as the criteria for determining if and when death has occurred.
      A number of important problems with the status quo are described, followed by a
      series of recommendations to address these problems. CONCLUSIONS: The legal
      deficiencies regarding the definition and determination of death in Canada may
      place health care providers at risk of civil or criminal liability, discourage
      potential organ donation, and frustrate the wishes of some individuals to donate
      their organs. The definition and criteria for the determination of death should
      be clearly set out in legislation. In addition, the current use of non-heart
      beating donor protocols in Canada will remain inconsistent with Canadian law
      until more persuasive evidence on the potential return of cardiac function after
      cardiac arrest is gathered and made publicly available or until a concrete
      proposal to abandon the dead donor rule and amend Canadian law is adopted
      following a process of public debate and intense multidisciplinary review.

PMID- 19585181
TI  - Comparisons of cystatin C with creatinine for evaluation of renal function in
      chronic kidney disease.
AB  - BACKGROUND: Because of the limitations of creatinine (Cr) as a marker for the
      glomerular filtration rate (GFR), cystatin C (CysC) has been proposed as an
      alternative substance. The aim here was to clarify the characteristics of CysC
      compared with Cr. METHODS: CysC and Cr were measured in 199 patients with chronic
      kidney disease. Regression analysis between CysC and Cr and comparisons of the
      effect of gender, inflammation, prescription of prednisolone, smoking and
      diabetes mellitus (DM) on these markers were performed. Sensitivity and
      specificity of CysC and Cr to discriminate estimated GFR of less than 50
      ml/min/1.73 m(2) were computed and evaluated by the receiver-operating
      characteristic curve (ROC). RESULTS: The correlation coefficient between natural
      logarithmic Cr [ln(Cr)] and ln(CysC) was higher than that between these variables
      per se (0.941 vs. 0.906). When Cr was lower than 1.10 mg/dl, CysC rose more
      sharply than Cr. CysC divided by Cr (CysC/Cr) was higher in females (1.35 +/-
      0.33 vs. 1.16 +/- 0.30; p < 0.001), in patients with elevated CRP (1.33 +/- 0.40
      vs. 1.21 +/- 0.29; p < 0.001) and in patients prescribed with prednisolone (1.42
      +/- 0.33 vs. 1.20 +/- 0.30; p < 0.001). A stepwise multiple linear regression
      model indicated that ln(CysC) was positively correlated with ln(Cr), age, female
      gender, prednisolone prescription, elevated CRP and DM (R = 0.964, p < 0.001).
      The area under the ROC curve of Cr was 0.900 and that of CysC was 0.925.
      CONCLUSION: CysC is a promising marker for GFR because it was not gender- or age
      related. However, inflammation, prednisolone and DM caused CysC to deviate higher
      than expected from GFR. CysC can rise sensitively in early renal dysfunction.

PMID- 19585186
TI  - CKD Clinical Practice Guidebook. The essence of treatment for CKD patients.

PMID- 19585179
TI  - Persistent adeno-associated virus 2 and parvovirus B19 sequences in post-mortem
      human cerebellum.
AB  - We previously reported in a large cohort (N = 104) of post-mortem tissues the
      detection of both the non-pathogenic adeno-associated virus (AAV2) in
      approximately 13% and the pathogenic human parvovirus B19 (B19) in approximately
      42% of human brains, particularly the dorsolateral prefrontal cortex. Multiple
      animal parvoviruses target the developing cerebellum (CBLM) resulting in
      hypoplasia and ataxia, but very little is known about the human parvoviruses and
      their ability to infect or cause disease in the CBLM. We have now confirmed in
      the above cohort the presence of AAV2 and B19 sequences in the CBLM. Our results
      show that approximately 27% and approximately 70% of human CBLM are positive by
      nested polymerase chain reaction for AAV2 and B19 sequences, respectively. We
      also document in a second cohort (N = 10) the presence of AAV2 (50%) and B19
      (100%) sequences in the CBLM and correlate our results for B19 with studies from
      matched sera. Eighty percent (80%) of this cohort was positive for anti-B19 IgG,
      while none were IgM+, suggesting that most individuals had been previously
      infected with B19 but none acutely. To our knowledge, this study is the first to
      demonstrate that both AAV2 and B19 sequences are present at relatively high
      frequencies in the CBLM and are likely due to persistent rather than acute
      infection. Further studies will lead to insights into AAV2- and/or B19-CBLM
      interactions including mechanisms of infection, persistence, and possibly
      neuropathology, including cerebellar hypoplasia and ataxia.

PMID- 19585214
TI  - Algorithm for in vitro diagnostic multivariate index assay.
AB  - Recently emerging diagnostic tools such as MammaPrint and oncotype-DX are
      beginning to have impact on clinical practice of breast cancer. They are based on
      gene expression profiling, i.e., gene expression analysis of a large number of
      genes. Their unique characteristic is the use of a score calculated from
      expression values of a number of genes, for which the Food and Drug
      Administration (FDA) created a new diagnostic category entitled "in vitro
      diagnostic multivariate index assay (IVDMIA)." In contrast to conventional
      biomarkers, IVDMIA requires an algorithm to calculate the diagnostic score. The
      linear classifier is the preferred algorithm. When the number of diagnostic genes
      is n, each tumor is represented by a point in an n-dimensional space made from
      gene expression values. Diagnostic algorithms (linear classifier) make an (n-1)
      dimensional plane in the n-dimensional space to separate two patient groups.
      Calculation of the diagnostic score is achieved by dimension reduction.
      Currently, IVDMIA is restricted to gene expression profiling, and will also be
      applied to malignancies other than breast cancer.

PMID- 19585212
TI  - Characterization of thymic masses using (18)F-FDG PET-CT.
AB  - BACKGROUND: The resectability and survival may be improved in thymoma and thymic
      carcinoma with multimodality therapy. Various diagnostic imaging modalities are
      required for accurate diagnosis and preoperative staging of thymic masses. The
      present prospective study was planned to evaluate if Fluorodeoxyglucose (FDG) PET
      CT can help differentiate various thymic lesions noted on conventional imaging
      modalities. METHODS: A prospective study was undertaken in 23 patients who had
      shown either an anterior mediastinal mass consistent with thymic origin or
      suspicious for a thymic mass on contrast-enhanced computed tomography scan. All
      patients underwent whole body FDG PET-CT after intravenous injection of 370 MBq
      of FDG. The interpretation of PET-CT images was based on the following criteria:
      FDG uptake (present or absent), SUVmax, pattern of uptake, invasion to
      surrounding structures, presence of metastasis and necrosis. The results of PET
      CT were correlated with the final histopathology following surgery. Statistical
      analysis was performed with SPSS 11.5 for Windows software. The mean SUVmax of
      the 3 groups of pathology was compared using the Kruskal-Wallis Test. RESULTS:
      Thymic hyperplasia had an enlarged thymus with mean SUVmax of 1.1. Low risk
      thymoma had large tumors and their mean SUVmax was 3. High risk thymoma had small
      tumors with mean SUVmax of 2.1. As a group, thymoma had mean SUVmax value of 2.3.
      All thymic carcinomas were large, and their mean SUVmax was 7. The difference
      between the mean SUVmax for thymic hyperplasia, thymoma and thymic carcinoma was
      statistically significant. The difference between the SUVmax of high risk and low
      risk thymoma was not significant. CONCLUSION: (18)F-FDG PET-CT can help
      characterize various thymic lesions noted on conventional imaging modalities.
      However, larger prospective studies are further required to substantiate these
      findings.

PMID- 19585213
TI  - Overexpression of Annexin II affects the proliferation, apoptosis, invasion and
      production of proangiogenic factors in multiple myeloma.
AB  - The abnormal expression of Annexin II (AnxA2, A2) has been associated with the
      development of tumors; however, its expression and function in multiple myeloma
      (MM) is less known. We compared the expression of AnxA2 in primary myeloma cells
      from MM patients with that in normal plasma cells from normal subjects and found
      that myeloma cells from patients had higher expression of AnxA2. Expression of
      AnxA2 was also significantly higher in MM cell lines U266 and RPMI8226, compared
      with other hematologic tumor cell lines. Transfecting U266 and RPMI8226 cells
      with the small interfering RNA (siRNA) that targets human AnxA2 led to
      significant downregulation of AnxA2 expression, which resulted in the decreased
      proliferation, invasive potential and increased apoptosis of U266 and RPMI8226
      cell lines. Silencing AnxA2 gene by siRNA also inhibited the expression of pro
      angiogenic molecules including VEGF-C, VEGF-R2, MMP-2, MMP-9, MT1-MMP and TIMP-2
      in the two cell lines. Our data suggested that the AnxA2 is overexpressed in MM
      patients and myeloma cell lines U266 and RPMI8226, and that AnxA2 overexpression
      appeared to affect the proliferation, apoptosis, invasive potential and
      production of pro-angiogenic factors in MM cell lines U266 and RPMI8226.

PMID- 19585215
TI  - Preoperative diagnosis of the axillary arch with multidetector row computed
      tomography and the axillary arch in association with anatomical problems of
      sentinel lymph node biopsy.
AB  - BACKGROUND: The purpose of this study was to describe the preoperative diagnosis
      of the axillary arch with multidetector row computed tomography (MDCT) in
      patients who underwent sentinel lymph node (SLN) biopsy. In addition, we
      investigated anatomical problems of SLN biopsy in the cases that diagnosed this
      anomaly. METHODS: From 2003 to 2008, combined procedures with blue dye SLN biopsy
      and MDCT-assisted axillary node sampling were performed in 550 clinically axilla
      negative patients with primary operable breast cancer. We use MDCT for not only
      the diagnosis of the axillary arch, but also the planning and navigation of SLN
      biopsy. RESULTS: The axillary arches were preoperatively diagnosed with MDCT in
      59 patients (10.8%) as follows: a single ordinary axillary arch (n = 44), another
      anomalous muscle besides the ordinary axillary arch (n = 13), and other rare
      axillary arches (n = 2). The SLN identification failure rate was 1.8% (9/491) for
      patients without the axillary arch and 5.1% (3/59) for patients with the axillary
      arch (chi-square test, P = 0.11). Three patients with an axillary arch in whom a
      SLN could not be identified were observed in 13 patients who had another
      anomalous muscle besides the ordinary axillary arch (3/13, 23.1%). In the
      examination of 56 patients with an axillary arch in whom a SLN was identified,
      variations of the SLN location and/or anomalous muscles covering a SLN were
      observed in 16 patients (28.5%). CONCLUSIONS: MDCT is useful for a diagnosis of
      the axillary arch. The axillary arch should be kept in mind during SLN biopsy
      because this anomaly would be related to anatomical variations that affect SLN
      biopsy.

PMID- 19585216
TI  - Effects of dexamethasone on the expression of beta(1)-, beta (2)- and beta (3)
      adrenoceptor mRNAs in skeletal and left ventricle muscles in rats.
AB  - Glucocorticoids are known to increase the density and mRNA levels of beta
      adrenoceptors (beta-AR) via the glucocorticoid receptor (GR) in many tissues.
      However, the effects of these changes in the skeletal and cardiac muscles remain
      relatively unknown. We have investigated the effects of dexamethasone on the
      expression of the beta(1)-, beta(2)-, and beta(3)-AR mRNAs and GR mRNA in fast
      twitch fiber-rich extensor digitorum longus (EDL), slow-twitch fiber-rich soleus
      (SOL), and left ventricle (LV) muscles by real-time quantitative RT-PCR. Male
      rats were divided into a dexamethasone group and control group. The weight, RNA
      concentration, and total RNA content of EDL muscle were 0.76-, 0.85-, and 0.65
      fold lower, respectively, in the dexamethasone group than in the control group.
      The weight, RNA concentration, and total RNA content of SOL muscle were 0.92-,
      0.87-, and 0.81-fold lower, respectively, in the dexamethasone group than in the
      control group; these differences were significant. However, the weight/body
      weight and total RNA content/body weight of LV muscle were 1.38- and 1.39-fold
      higher, respectively, in the dexamethasone group than in the control group,
      respectively; these differences were also significant. Dexamethasone
      significantly decreased GR mRNA expression in EDL muscle without changing the
      expression of the beta(1)-, beta(2)-, and beta(3)-AR mRNAs. However,
      dexamethasone significantly decreased the expressions of beta(2)-AR and GR mRNAs
      in SOL muscle and significantly increased beta(1)-AR mRNA expression in LV muscle
      without changing GR mRNA expression. These results suggest that the effects of
      dexamethasone on the expression of beta(1)- and beta(2)-AR mRNAs and muscle mass
      depend on the muscle contractile and/or constructive types.

PMID- 19585217
TI  - Physiological and biochemical responses of green microalgae from different
      habitats to osmotic and matric stress.
AB  - Growth of five aeroterrestrial green algal strains (Trebouxiophyceae) in response
      to changing water availabilities-caused by osmotic (ionic) and matric
      (desiccation) stresses-was investigated in comparison with a freshwater and a
      marine strain. All investigated algae displayed good growth under brackish
      conditions while four out of the five aeroterrestrial strains even grew well
      under full marine conditions (28-40 psu). The comparison between growth responses
      in liquid medium, on solid agarose, and on glass fiber filters at 100% air
      humidity indicated a broad growth tolerance of aeroterrestrial algae towards
      diminished water availability. While two aeroterrestrial strains even grew better
      on solid medium which mimics natural biofilm conditions, the aquatic strains
      showed significant growth inhibition under matric stress. Except Stichococcus
      sp., which contained the C6-polyol sorbitol, all other aeroterrestrial green
      algae investigated synthesized and accumulated the C5-polyol ribitol in response
      to osmotic stress. Using (13)C NMR spectroscopy and HPLC, it could be verified
      that ribitol functions as an osmotically regulated organic solute. This is the
      first proof of ribitol in free-living aeroterrestrial green algae. The
      biochemical capability to synthesize polyols under environmental stress
      conditions seems to support algal life outside aquatic habitats.

PMID- 19585218
TI  - Analogues of both Leu- and Met-enkephalin containing a constrained dipeptide
      isostere prepared from a Baylis-Hillman adduct.
AB  - An efficient route was developed for the synthesis of the Fmoc-protected
      dipeptide 4, isostere of Gly-Gly containing an alpha-methylene beta-amino acid;
      the conformationally restricted analogues of Leu-enkephalin, 3a, and Met
      enkephalin, 3b, respectively, were prepared by changing 4 for Gly(2)-Gly(3) in
      the native compounds 3a and 3b whose biological activities were significantly
      lower than the parent compounds.

PMID- 19585219
TI  - Abstracts of the 11th International Congress on Amino Acids, Peptides and
      Proteins. August 3-7, 2009. Vienna, Austria.

PMID- 19585220
TI  - Anomalous origin of circumflex arteries evaluated with MDCT.

PMID- 19585221
TI  - Procalcitonin in patients with acute coronary syndromes and cardiogenic shock
      submitted to percutaneous coronary intervention.
AB  - Procalcitonin (PCT) is known to be a biological diagnostic marker for severe
      sepsis, or septic shock in critically ill patients. There are still contrasting
      data about a role of procalcitonin in patients with acute myocardial infarction
      or cardiogenic shock, and in those with acute coronary syndromes, that is, non-ST
      elevation myocardial infarction or unstable angina. We evaluated plasma levels of
      procalcitonin and C-reactive protein (CRP) in 52 patients admitted to our
      intensive cardiac care unit (ICCU): 14 patients with cardiogenic shock (CS)
      following ST-elevation myocardial infarction (STEMI), 15 patients with
      uncomplicated ST-elevation myocardial infarction (STEMI), and 24 with non-ST
      elevation myocardial infarction or unstable angina (NSTEMI/UA). In all patients,
      infective processes were excluded. Procalcitonin values were significantly higher
      in CS patients with respect to the other two subgroups (P < 0.001, P < 0.001)
      while CRP levels were higher than NSTEMI/UA patients (P < 0.001) but not with
      respect to STEMI patients (P = 0.063). No correlations were found in cardiogenic
      shock patients between CRP and PCT values (R = 0.02; P = 0.762, ns).
      Procalcitonin levels measured on ICCU admission are significantly higher in
      patients with cardiogenic shock following the acute myocardial infarction, and
      they are not correlated with those of CRP. The degree of myocardial ischemia
      (clinically indicated by the whole spectrum of ACS, from unstable angina to
      cardiogenic shock ST-elevation following myocardial infarction) and the related
      inflammatory-induced response are better reflected by CRP (which was positive in
      most acute cardiac care patients of all our subgroups), than by PCT which seems
      more reflective of a higher degree of inflammatory activation, being positive
      only in all CS patients.

PMID- 19585222
TI  - Interleukin 7 receptor alpha as a potential therapeutic target in
      transplantation.
AB  - Drugs targeting memory lymphocytes may allow for a better control of rejection in
      transplantation, particularly in immunized patients. In this article the
      rationale of targeting interleukin 7 receptor alpha (IL-7Ralpha), a molecule
      expressed by both memory and naive T cells, is reviewed in the context of
      transplantation. Whereas naive T cells are partly responsible for acute rejection
      and are targeted by current immunosuppressive drugs that block costimulatory
      signals (cyclosporine A, anti-CD3 antibody, anti-CD52 antibody, anti-thymocyte
      globulin, etc.), memory T cells are resistant to costimulation blockade. As such,
      memory cells are an obstacle to experimental tolerance induction and may be
      involved in chronic rejection. There is thus much scientific interest in
      developing molecules able to target these cells. The role of the IL-7/IL-7Ralpha
      pathway in transplantation rejection has been suggested by the effect of an anti
      IL-7 monoclonal antibody which, when associated with costimulation blockade,
      prolonged heart allograft survival in mice. Here the hypothesis that targeting IL
      7Ralpha would preserve effector T cells that are less dependent on IL-7 for
      survival while sparing regulatory CD4+ CD25high IL-7Ralpha(low) T cells is
      discussed. An anti-IL-7Ralpha antibody could also help achieve allograft
      tolerance by reducing alloreactive cells.

PMID- 19585223
TI  - A human brainstem glioma xenograft model enabled for bioluminescence imaging.
AB  - Despite the use of radiation and chemotherapy, the prognosis for children with
      diffuse brainstem gliomas is extremely poor. There is a need for relevant
      brainstem tumor models that can be used to test new therapeutic agents and
      delivery systems in pre-clinical studies. We report the development of a
      brainstem-tumor model in rats and the application of bioluminescence imaging
      (BLI) for monitoring tumor growth and response to therapy as part of this model.
      Luciferase-modified human glioblastoma cells from five different tumor cell
      sources (either cell lines or serially-passaged xenografts) were implanted into
      the pontine tegmentum of athymic rats using an implantable guide-screw system.
      Tumor growth was monitored by BLI and tumor volume was calculated by three
      dimensional measurements from serial histopathologic sections. To evaluate if
      this model would allow detection of therapeutic response, rats bearing brainstem
      U-87 MG or GS2 glioblastoma xenografts were treated with the DNA methylating
      agent temozolomide (TMZ). For each of the tumor cell sources tested, BLI
      monitoring revealed progressive tumor growth in all animals, and symptoms caused
      by tumor burden were evident 26-29 days after implantation of U-87 MG, U-251 MG,
      GBM6, and GBM14 cells, and 37-47 days after implantation of GS2 cells.
      Histopathologic analysis revealed tumor growth within the pons in all rats and
      BLI correlated quantitatively with tumor volume. Variable infiltration was
      evident among the different tumors, with GS2 tumor cells exhibiting the greatest
      degree of infiltration. TMZ treatment groups were included for experiments
      involving U-87 MG and GS2 cells, and in each case TMZ delayed tumor growth, as
      indicated by BLI monitoring, and significantly extended survival of animal
      subjects. Our results demonstrate the development of a brainstem tumor model in
      athymic rats, in which tumor growth and response to therapy can be accurately
      monitored by BLI. This model is well suited for pre-clinical testing of
      therapeutics that are being considered for treatment of patients with brainstem
      tumors.

PMID- 19585225
TI  - Effect of HCl concentrations on apatite-forming ability of NaOH-HCl- and heat
      treated titanium metal.
AB  - Titanium (Ti) metal was treated with water or HCl solutions after 5 M NaOH
      solution treatment and then subjected to heat treatment at 600 degrees C. The
      apatite-forming abilities of the treated Ti metals were examined in simulated
      body fluid. The apatite-forming ability of the Ti metal subjected to NaOH, water
      and heat treatment was lower than that of just NaOH and heat treatments. Ti
      metals subjected to NaOH, HCl and heat treatment showed apatite-forming
      abilities, which increased with increasing HCl concentrations up to the same
      level as that of NaOH- and heat-treated Ti metal. The former did not show a
      decrease in its apatite-forming ability, even in a humid environment for a long
      period, whereas the latter decreased its ability. The increase in the apatite
      forming ability with increasing HCl concentrations suggests a different mechanism
      of apatite formation from that previously proposed.

PMID- 19585224
TI  - Hyperglycemic oxoaldehyde, glyoxal, causes barrier dysfunction, cytoskeletal
      alterations, and inhibition of angiogenesis in vascular endothelial cells:
      aminoguanidine protection.
AB  - Vascular endothelium is vulnerable to the attack of glucose-derived oxoaldehydes
      (glyoxal and methylglyoxal) during diabetes, through the formation of advanced
      glycation end products (AGEs). Although aminoguanidine (AG) has been shown to
      protect against the AGE-induced adverse effects, its protection against the
      glyoxal-induced alterations in vascular endothelial cells (ECs) such as
      cytotoxicity, barrier dysfunction, and inhibition of angiogenesis has not been
      reported and we investigated this in the bovine pulmonary artery ECs (BPAECs).
      The results showed that glyoxal (1-10 mM) significantly induced cytotoxicity and
      mitochondrial dysfunction in a dose- and time-dependent (4-12 h) fashion in ECs.
      Glyoxal was also observed to significantly inhibit EC proliferation. The study
      also revealed that glyoxal induced EC barrier dysfunction (loss of trans
      endothelial electrical resistance), actin cytoskeletal rearrangement, and tight
      junction alterations in BPAECs. Furthermore, the results revealed that glyoxal
      significantly inhibited in vitro angiogenesis on the Matrigel. For the first
      time, this study demonstrated that AG significantly protected against the glyoxal
      induced cytotoxicity, barrier dysfunction, cytoskeletal rearrangement, and
      inhibition of angiogenesis in BPAECs. Therefore, AG appears as a promising
      protective agent in the treatment of AGE-induced vascular endothelial alterations
      and dysfunction during diabetes, presumably by blocking the reactivity of the
      sugar-derived dicarbonyls such as glyoxal and preventing the formation of AGEs.

PMID- 19585226
TI  - Synthesis and characterization of biocomposites with different hydroxyapatite
      collagen ratios.
AB  - Hydroxyapatite (HA)-type I collagen (Col) composite is a tissue-engineered bone
      graft which can act as a carrier or a template structure for cells or any other
      agents. In this paper, the effect of Col ratio on the scaffold structure and
      composition was analyzed. Scaffolds composed by HA/Col with different weight
      ratios (80:20; 50:50; 20:80, and 10:90) were produced by the precipitation method
      at pH 8-9, 37 degrees C and 6 h of ripening. Using X-ray diffraction data, the
      Rietveld structure refinement showed that the size of HA crystals along the c
      axis direction (002) decreases significantly in the presence of Col. Thus, the HA
      crystal shape turned from needle-like in pure HA, into spherical, in the 10:90
      composite due to Col fibrillogenesis. The homogeneity of the composite was
      significantly dependent on the amount of Col in it. HA/Col 20/80 composite
      presented HA particles in a more homogenous way. Such a biocomposite was
      successfully produced in a rapid way and it is potentially useful for both small
      tissue repairs and engineering.

PMID- 19585228
TI  - A collaborative approach to genetic testing: a community hospital's experience.
AB  - The field of cancer genetics is evolving rapidly, and much has changed over the
      past ten years in the way services are being provided and by whom they are being
      provided. We recount here our experience with the evolution of cancer genetic
      services in a community setting, focusing on collaboration with non-genetics
      providers to offer genetic testing for hereditary cancer. This approach allows
      for the most effective use of genetic counselors' expertise for challenging
      cases, and enables the patient to remain within their community to allow for
      better access to resources for long-term follow-up.

PMID- 19585229
TI  - Does post-identification feedback affect evaluations of eyewitness testimony and
      identification procedures?
AB  - Two experiments were conducted to test whether post-identification feedback
      affects evaluations of eyewitnesses. In Experiment 1 (N = 156), evaluators viewed
      eyewitness testimony. They evaluated witnesses who received confirming post
      identification feedback as more accurate and more confident, among other
      judgments, compared with witnesses who received disconfirming post-identification
      feedback or no feedback. This pattern persisted regardless of whether the
      witness's confidence statement was included in the testimony. In Experiment 2 (N
      = 161), witness evaluators viewed the actual identification procedure in which
      feedback was delivered. Instructions to disregard the feedback were manipulated.
      Again, witnesses who received confirming feedback were assessed more positively.
      This pattern occurred even when witness evaluators received instructions to
      disregard the feedback. These experiments are the first to confirm researchers'
      assumptions that feedback effects on witnesses translate to changes in judgments
      of those witnesses.

PMID- 19585230
TI  - Repeated eyewitness identification procedures: memory, decision making, and
      probative value.
AB  - Two experiments examined the effects of multiple identification procedures on
      identification responses, confidence, and similarity relationships. When the
      interval between first and second identification procedures was long (Experiment
      1), correct and false identifications increased, but the probative value of a
      suspect identification changed little; consistent witnesses were more confident
      than inconsistent witnesses; and the similarity relationships between suspect and
      foils were unchanged. When the interval between first and second identification
      procedures was short (Experiment 2), suspect identification rates changed little,
      but foil identifications increased significantly; confidence for all
      identifications increased; consistent witnesses were more confident than
      inconsistent witnesses; and similarity relationships changed such that witnesses
      were less likely to identify the suspect as being the best match to the
      perpetrator.

PMID- 19585232
TI  - Tumor necrosis factor alpha and interleukin 10 promoter polymorphisms in Mexican
      patients with restenosis after coronary stenting.
AB  - To test for an association with risk for restenosis after coronary stent
      placement, the TNF-alpha and IL-10 polymorphisms were analyzed by 5' exonuclease
      TaqMan assays in 162 patients who initially underwent coronary stenting. Analysis
      of basal and procedure coronary angiographies revealed a higher proportion of
      restenosis in lesions treated with bare metal stents compared with those treated
      with drug-eluting stents (P < 0.001). Distribution of TNF-alpha genotypes was
      similar in patients with and without restenosis. The IL-10 polymorphisms showed a
      moderate protective trend of the -819 TT genotype against restenosis when the
      lesions were analyzed (P = 0.071, OR = 0.471). Multivariate analysis confirmed a
      protective role for drug-eluting stents (P < 0.001, OR = 0.199) and the -819 TT
      genotype (P = 0.037, OR = 0.391). These results suggest the IL-10 -819 TT
      genotype has a protective role against in-stent restenosis.

PMID- 19585227
TI  - Osteoimmunology: crosstalk between the immune and bone systems.
AB  - INTRODUCTION: The interaction between the immune and skeletal systems has long
      been acknowledged, but investigation into rheumatoid arthritis (RA) as well as
      the various bone phenotypes found in immunocompromised gene-deficient mice has
      highlighted the importance of the dynamic interplay between the two systems. This
      has led to the recent emergence and subsequent rapid evolution of the field of
      osteoimmunology. BONE DESTRUCTION WITH ARTHRITIS AS A RANKL DISEASE: In the bone
      destruction associated with RA, IL-17-producing helper T cells (T(H)17) play a
      major role by inducing receptor activator of nuclear factor-kappaB ligand
      (RANKL). RANKL stimulates osteoclastogenesis through nuclear factor of activated
      T cells cytoplasmic 1 (NFATc1), which is well known as a crucial regulator of
      immunity. NEW PLAYERS IN OSTEOIMMUNOLOGY: In addition to cellular interactions
      via cytokines, the immune and skeletal systems share various molecules, including
      transcription factors, signaling molecules, and membrane receptors. CONCLUSION:
      The scope of osteoimmunology has grown to encompass a wide range of molecular and
      cellular interactions, the elucidation of which will provide a scientific basis
      for future therapeutic approaches to diseases of both the immune and skeletal
      systems.

PMID- 19585234
TI  - The contribution of mere recognition to the p300 effect in a concealed
      information test.
AB  - In two experiments, we investigated the role of mere recognition in a P300 based
      CIT. Mere recognition was isolated by having participants respond based on an
      irrelevant dimension of the stimuli. In Experiment 1 stimuli consisted of
      familiar and unfamiliar faces, with a dot placed on the left or the right cheek.
      Participants responded according to dot location. In the second experiment,
      participants were presented with autobiographical information, alternated with
      irrelevant stimuli, while instructed to respond based on the case of the stimuli.
      Results showed that with both familiar faces, and autobiographical information,
      mere recognition was sufficient to elicit a P300.

PMID- 19585235
TI  - Bisphosphonate-related osteonecrosis of the jaw in randomized clinical trials.

PMID- 19585233
TI  - Intrathecal NGF administration reduces reactive astrocytosis and changes
      neurotrophin receptors expression pattern in a rat model of neuropathic pain.
AB  - Nerve growth factor (NGF), an essential peptide for sensory neurons, seems to
      have opposite effects when administered peripherally or directly to the central
      nervous system. We investigated the effects of 7-days intrathecal (i.t.) infusion
      of NGF on neuronal and glial spinal markers relevant to neuropathic behavior
      induced by chronic constriction injury (CCI) of the sciatic nerve. Allodynic and
      hyperalgesic behaviors were investigated by Von Frey and thermal Plantar tests,
      respectively. NGF-treated animals showed reduced allodynia and thermal
      hyperalgesia, compared to control animals. We evaluated on lumbar spinal cord the
      expression of microglial (ED-1), astrocytic (GFAP and S-100beta), and C- and
      Adelta-fibers (SubP, IB-4 and Cb) markers. I.t. NGF treatment reduced reactive
      astrocytosis and the density of SubP, IB4 and Cb positive fibers in the dorsal
      horn of injured animals. Morphometric parameters of proximal sciatic nerve stump
      fibers and cells in DRG were also analyzed in CCI rats: myelin thickness was
      reduced and DRG neurons and satellite cells appeared hypertrophic. I.t. NGF
      treatment showed a beneficial effect in reversing these molecular and
      morphological alterations. Finally, we analyzed by immunohistochemistry the
      expression pattern of neurotrophin receptors TrkA, pTrkA, TrkB and p75(NTR).
      Substantial alterations in neurotrophin receptors expression were observed in the
      spinal cord of CCI and NGF-treated animals. Our results indicate that i.t. NGF
      administration reverses the neuro-glial morphomolecular changes occurring in
      neuropathic animals paralleled by alterations in neurotrophin receptors ratio,
      and suggest that NGF is effective in restoring homeostatic conditions in the
      spinal cord and maintaining analgesia in neuropathic pain.

PMID- 19585236
TI  - Controversial BRCA1 allelotypes in commonly used breast cancer cell lines.

PMID- 19585237
TI  - Association of BTLA gene polymorphisms with the risk of malignant breast cancer
      in Chinese women of Heilongjiang Province.
AB  - B and T lymphocyte attenuator (BTLA) is an immunoinhibitory receptor with the
      ability to deliver inhibitory signals for suppressing lymphocyte activation. To
      identify the influences of BTLA gene polymorphisms on the risk of sporadic breast
      cancer, a case-control study was conducted in women from northeast of China,
      Heilongjiang Province. We genotyped five SNPs (rs9288952, rs2931761, rs2633562,
      rs2705535 and rs1844089) in BTLA gene among exons and introns. Our research
      groups consist of 592 patients with breast cancer and 506 age/sex-matched healthy
      controls. Genotypes were determined by the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and polymerase chain reaction with
      confronting two-pair primer (PCR-CTPP) methods. Data were analyzed using the chi
      square test by EXCEL, SPSS and Haploview softwares. The frequencies of BTLA
      rs1844089 CT and rs2705535 AG were higher in patients than in controls (P =
      0.0164; P = 0.0031), and rs1844089 CC, rs2705535 GG and rs9288952 CC genotypes
      had lower incidences in patients than in controls (P = 0.0483; P = 0.0098; P =
      0.0400). The frequency of haplotype CAAAT was significantly higher in patients (P
      = 0.0112). Strong association was shown between five SNPs of BTLA gene and tumor
      size, estrogen receptor (ER), progesterone receptor (PR), C-erbB-2 and P53
      statuses. Strong association was observed between tumor size, ER, PR, P53 and the
      CAGAT(P = 0.012), TAAGT(P = 0.0378), CAGAT(P = 0.0013), CAAGT(P = 0.0373) and
      CAAAT(P = 0.0306) haplotypes. These results primarily suggested that BTLA gene
      polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese
      women in northeast of Heilongjiang Province.

PMID- 19585238
TI  - Stories behind the symptoms: a qualitative analysis of the narratives of 9/11
      rescue and recovery workers.
AB  - A qualitative study of the experiences of rescue and recovery workers/volunteers
      at Ground Zero following the terrorist attacks of 9/11/01 is reported.
      Information was extracted from a semi-structured clinical evaluation of 416
      responders who were the initial participants in a large scale medical and mental
      health screening and treatment program for 9/11 responders. Qualitative analysis
      revealed themes that spanned four categories- occupational roles, exposures,
      attitudes/experiences, and outcomes related to the experience of Ground Zero.
      Themes included details regarding Ground Zero roles, grotesque experiences such
      as smells, the sense of the surreal nature of responding, and a turning to
      rituals to cope after leaving Ground Zero. These findings personalize the symptom
      reports and diagnoses that have resulted from the 9/11 responders' exposure to
      Ground Zero, yielding richer information than would otherwise be available for
      addressing the psychological dimensions of disasters. This work shows that large
      scale qualitative surveillance of trauma-exposed populations is both relevant and
      feasible.

PMID- 19585239
TI  - Motion compensation in hand-held laser scanning for surface modeling in plastic
      and reconstructive surgery.
AB  - The purpose of this work is to develop a new integrated methodology for breast
      morphology assessment in plastic and reconstructive surgery. Such a methodology
      comprises hand-held laser scanning with active compensation of breathing motion
      and involuntary movements, in order to obtain a thorough and artifacts-free
      representation of patient breast shape. This was obtained by tracking surface
      motion with a configuration of passive markers fitted on the patient's thoraco
      abdominal region. The proposed method, based on a mapping procedure, has been
      compared with respiratory gating, that is commonly used in radiotherapy and
      biomedical imaging applications. The results show that the implemented procedure
      is adequately able to compensate for motion, resulting in quantitative surface
      description to be used for clinical evaluation.

PMID- 19585240
TI  - Assessing the susceptibility to local buckling at the femoral neck cortex to age
      related bone loss.
AB  - Although it is known that long cortical bone structurally alter their area moment
      of inertia with age related bone loss maintaining their bending strength, the
      incidence of fragility fractures associated with cortical thinning still
      prevails. We hypothesize that cortical thinning with aging increases the local
      buckling susceptibility under abnormal or eccentric loads, and initiates
      fracture. The paper presents a series of 3D geometrical model derived from CT
      scans of a human femoral neck used to simulate age-related bone loss. The purpose
      of the model is to predict the susceptibility of local buckling at the femoral
      neck in falls by elderly folks. Geometric three-dimensional models of femoral
      neck cortices were developed from 7 human cadaver femurs (4 female, 3 male, 52-68
      years). Three age related femoral neck models were simulated by either reducing
      (young age-related model) or increasing (old age-related model) the outer
      cortical surfaces in the radial-direction, by 1-mm. The control model was the
      middle-age related model. The inner cortex diameter was also adjusted to
      equilibrate the compressive stresses, based on the load-profile of a single
      legged stance. Based on the old age related model, two additional "fragile"
      models were simulated by reducing the compressive load profile by 10 and 20%
      changing the inner cortex diameter, respectively. Using these models for each
      specimen, the consequence of a fall on the greater trochanter was evaluated. The
      Finite Strip Method (FSM) was used to investigate the association between local
      buckling at the femoral neck and the load to failure. Under constant loading,
      buckling progressively reduced the load to failure with aging, as seen in 2/7 of
      the middle age (by 9-15%) and 5/7 of the old age (by 7-32%) related models. In
      the fragile models, a 51% reduction in the load to failure was noted. Structural
      adaptation to age-related bone loss might preserves the bending strength under
      physiologic loads, but cortical thinning effects the buckling ratio reaching a
      critical threshold that would make the bone susceptible to local buckling at the
      femoral neck increasing the risk of fracture in a fall.

PMID- 19585241
TI  - In vivo dynamic deformation of the mitral valve annulus.
AB  - Though mitral valve (MV) repair surgical procedures have increased in the United
      States [Gammie, J. S., et al. Ann. Thorac. Surg. 87(5):1431-1437, 2009; Nowicki,
      E. R., et al. Am. Heart J. 145(6):1058-1062, 2003], studies suggest that altering
      MV stress states may have an effect on tissue homeostasis, which could impact the
      long-term outcome [Accola, K. D., et al. Ann. Thorac. Surg. 79(4):1276-1283,
      2005; Fasol, R., et al. Ann. Thorac. Surg. 77(6):1985-1988, 2004; Flameng, W., P.
      Herijgers, and K. Bogaerts. Circulation 107(12):1609-1613, 2003; Gillinov, A. M.,
      et al. Ann. Thorac. Surg. 69(3):717-721, 2000]. Improved computational modeling
      that incorporates structural and geometrical data as well as cellular components
      has the potential to predict such changes; however, the absence of important
      boundary condition information limits current efforts. In this study, novel high
      definition in vivo annular kinematic data collected from surgically implanted
      sonocrystals in sheep was fit to a contiguous 3D spline based on quintic-order
      hermite shape functions with C(2) continuity. From the interpolated
      displacements, the annular axial strain and strain rate, bending, and twist along
      the entire annulus were calculated over the cardiac cycle. Axial strain was shown
      to be regionally and temporally variant with minimum and maximum values of -10
      and 4%, respectively, observed. Similarly, regionally and temporally variant
      strain rate values, up to 100%/s contraction and 120%/s elongation, were
      observed. Both annular bend and twist data showed little deviation from unity
      with limited regional variations, indicating that most of the energy for
      deformation was associated with annular axial strain. The regionally and
      temporally variant strain/strain rate behavior of the annulus are related to the
      varied fibrous-muscle structure and contractile behavior of the annulus and
      surrounding ventricular structures, although specific details are still
      unavailable. With the high resolution shape and displacement information
      described in this work, high fidelity boundary conditions can be prescribed in
      future MV finite element models, leading to new insights into MV function and
      strategies for repair.

PMID- 19585243
TI  - The Columbia-Harlem Homeless Medical Partnership: a new model for learning in the
      service of those in medical need.
AB  - Though altruism and patient advocacy are promoted in medical education curricula,
      students are given few opportunities to develop these skills. Student-run clinics
      focusing on the health needs of the underserved can provide important health
      services to needy patients while providing students with career-influencing
      primary care experiences. The Columbia-Harlem Homeless Medical Partnership
      (CHHMP)-a project initiated by medical students to provide primary care to
      Northern Manhattan's homeless population-serves as a new model of service
      learning in medical education. Unlike many other student-run clinics, CHHMP has
      developed direct patient outreach, continuous care (stable "student-patient
      teams" and a weekly commitment for all volunteers), and regular internal data
      review. Chart review data presented demonstrate the project's success in
      providing care to the clinic's target population of homeless and unstably housed
      patients. Targeted outreach efforts among clients have increased rates of patient
      follow-up at each subsequent review period. Additionally, CHHMP has used review
      data to develop services concordant with identified patient needs (psychiatric
      care and social services). CHHMP has recruited a committed group of volunteers
      and continues to engender an interest in the health needs of the underserved
      among students. Not only does CHHMP provide a "medical home" for homeless
      patients, it also provides a space in which students can develop skills
      unaddressed in large teaching hospitals. This project, a "win-win" for patients
      and students, serves as a unique model for community health-based service
      learning in medical education.

PMID- 19585244
TI  - Physical activity resource attributes and obesity in low-income African
      Americans.
AB  - More than two thirds of Americans are overweight or obese, and African Americans
      are particularly vulnerable to obesity when compared to Caucasians. Ecological
      models of health suggest that lower individual and environmental socioeconomic
      status and the built environment may be related to health attitudes and behaviors
      that contribute to obesity. This cross-sectional study measured the direct
      associations of neighborhood physical activity resource attributes with body mass
      index (BMI) and body fat among low-income 216 African Americans (Mean (M) age =
      43.5 years, 63.9% female) residing in 12 public housing developments. The
      Physical Activity Resource Assessment instrument measured accessibility,
      incivilities, and the quality of features and amenities of each physical activity
      resource within an 800-m radius around each housing development. Sidewalk
      connectivity was measured using the Pedestrian Environment Data Scan instrument.
      Ecological multivariate regression models analyzed the associations between the
      built environment attributes and resident BMI and body fat at the neighborhood
      level. Sidewalk connectivity was associated with BMI (M = 31.3 kg/m(2); p <
      0.05). Sidewalk connectivity and resource accessibility were associated with body
      fat percentage (M = 34.8%, p < 0.05). Physical activity resource attributes and
      neighborhood sidewalk connectivity were related to BMI and body fat among low
      income African Americans living in housing developments.

PMID- 19585245
TI  - Cytogenetic survey of species of two distinct genera of Iberian nases
      (Cyprinidae, Leuciscinae) that hybridize extensively in nature. I. Evidence of a
      similar and conserved chromosome pattern with some few species-specific markers
      at macro-structural level.
AB  - Pseudochondrostoma duriense and Pseudochondrostoma polylepis hybridize
      extensively with Achondrostoma oligolepis in natural populations. In this first
      survey, karyotypes were comparatively analyzed by C-, AgNOR- and CMA(3)-banding
      procedures in pure (non-introgressed) fish specimens. Leuciscinae pattern was
      evidenced in the three species: metacentrics and submetacentrics dominance, a big
      subtelo/acrocentric (marker) chromosome pair and a 2n = 50; small macro
      structural differences were observed. Heterochromatin was centromere-associated.
      Exceptions were found at sm1 and st/a1 long arms and at m1, sm3 and sm6 short
      arms. The st/a1 band was telomeric in the straight-mouth nases and sub-terminal
      in A. oligolepis. Multiple NORs of heterochromatic nature were found in sm pairs
      of the three species. Signals were telomeric except for one pair in A.
      oligolepis. Two to four structural and two functional NORs were found in P.
      duriense and P. polylepis, and four to six structural and four functional NORs in
      A. oligolepis. Species-specific markers will prove useful in hybrid zones'
      cytogenetic characterization and for in-depth studies of genome compatibility
      related issues in future studies.

PMID- 19585246
TI  - Impacts of intensive agricultural irrigation and livestock farming on a semi-arid
      Mediterranean catchment.
AB  - Irrigation return flows (IRF) are a major contributor of non-point source
      pollution to surface and groundwater. We evaluated the effects of irrigation on
      stream hydrochemistry in a Mediterranean semi-arid catchment (Flumen River, NE
      Spain). The Flumen River was separated into two zones based on the intensity of
      irrigation activities in the watershed. General linear models were used to
      compare the two zones. Relevant covariables (urban sewage, pig farming, and
      gypsum deposits in the basin) were quantified with the help of geographic
      information system techniques, accompanied by ground-truthing. High variability
      of the water quality parameters and temporal dynamics caused by irrigation were
      used to distinguish the two river reaches. Urban activity and livestock farming
      had a significant effect on water chemistry. An increase in the concentration of
      salts (240-541 microS.cm(-1) more in winter) and nitrate (average concentrations
      increased from 8.5 to 20.8 mg.l(-1) during irrigation months) was associated with
      a higher level of IRF. Those river reaches more strongly influenced by urban
      areas tended to have higher phosphorus (0.19-0.42 mg.l(-1) more in winter)
      concentrations. These results support earlier research about the significant
      consequences to water quality of both urban expansion and intensive agricultural
      production in arid and semi-arid regions. Data also indicate that salinization of
      soils, subsoils, surface water, and groundwater can be an unwelcome result of the
      application of pig manure for fertilization (increase in sodium concentration in
      77.9 to 138.6 mg.l(-1)).

PMID- 19585247
TI  - Professional competencies in health sciences education: from multiple
      intelligences to the clinic floor.
AB  - Nontechnical competencies identified as essential to the health professional's
      success include ethical behavior, interpersonal, self-management, leadership,
      business, and thinking competencies. The literature regarding such diverse
      topics, and the literature regarding "professional success" is extensive and wide
      ranging, crossing educational, psychological, business, medical and vocational
      fields of study. This review is designed to introduce ways of viewing
      nontechnical competence from the psychology of human capacity to current
      perspectives, initiatives and needs in practice. After an introduction to the
      tensions inherent in educating individuals for both biomedical competency and
      "bedside" or "cageside" manner, the paper presents a brief overview of the major
      lines of inquiry into intelligence theory and how theories of multiple
      intelligences can build a foundation for conceptualizing professional and life
      skills. The discussion then moves from broad concepts of intelligence to more
      specific workplace skill sets, with an emphasis on professional medical
      education. This section introduces the research on noncognitive variables in
      various disciplines, the growing emphasis on competency based education, and the
      SKA movement in veterinary education. The next section presents the evidence that
      nontechnical, noncognitive or humanistic skills influence achievement in academic
      settings, medical education and clinical performance, as well as the challenges
      faced when educational priorities must be made.

PMID- 19585248
TI  - QSAR allows going a step further by measuring and quantifying cause-effect
      information to chemical structures.

PMID- 19585249
TI  - Adenovirus vector production using low-multiplicity infection of 293 cells.
AB  - The use of low-multiplicity infection of 293 cells in static culture with regular
      medium replacement was investigated for efficient large-scale production of
      adenovirus vectors for gene therapy applications. An adenovirus vector carrying
      the enhanced green fluorescent protein gene (Ad EGFP) was used to infect 293-F
      cells at a low multiplicity of infection (MOI) of 0.00001-0.1 transductional unit
      (TU) cell(-1). The cells, which have the ability to grow in suspension, were
      incubated in T-flasks and the serum-free culture medium was replaced with fresh
      medium via centrifugation every 2 days. Because only a small proportion of cells
      were initially infected at low MOIs (<1 TU cell(-1)), uninfected cells continued
      to grow until they were infected by progeny adenoviruses released from previously
      infected cells. When 293-F cells at a relatively low density of 1 x 10(5) cells
      cm(-3) were infected with Ad EGFP at a low MOI of 0.001 TU cell(-1), the vector
      yield was 2.7-fold higher than the maximum yield obtained with high-multiplicity
      infection (MOI = 10 TU cell(-1)) in batch culture. These results indicate that
      efficient adenovirus vector production using low MOIs is achieved by minimization
      of either nutrient depletion and/or accumulation of inhibitory metabolites in the
      culture medium.

PMID- 19585250
TI  - Role of the serotonin transporter in heart valve development and disease.

PMID- 19585251
TI  - The quality of raw and cured hams as affected by the dietary replacement of soya
      bean meal with alternative protein sources.

PMID- 19585252
TI  - Effect of stunning voltage and scalding method on the incidence of the "red skin"
      defect of Parma ham.

PMID- 19585253
TI  - Extension and validation of the UNI EN 1786 method for electron spin resonance
      (ESR) detection of irradiated turkey, pork and horse meat samples.

PMID- 19585254
TI  - Lipid changes in Italian salami induced by irradiation.

PMID- 19585255
TI  - Plasma atrial natriuretic peptide (proANP 31-67), B-type natriuretic peptide (Nt
      proBNP) and endothelin-1 (ET-1) concentrations in dogs with chronic degenerative
      valvular disease (CDVD).

PMID- 19585256
TI  - Biopharmaceutical profile of tramadol in the dog.

PMID- 19585257
TI  - Evaluation of the muscular relaxant effect of dexmedetomidine or medetomidine in
      cats.

PMID- 19585258
TI  - Analysis of variability and antigenic peptide prediction of E2 BVDV glycoprotein
      in a mucosal-disease affected animal.

PMID- 19585259
TI  - Equine Gasterophilosis in Sardinia: annual trend of bot eggs laying in different
      topographic regions of the horse.

PMID- 19585260
TI  - Immunolocalization of INSL3 in dog foetal Leydig cells and the LGR8 receptor in
      the gubernaculum testis.

PMID- 19585261
TI  - Evolutionary approach to communication between humans and dogs.
AB  - Dogs and humans have been sharing a common environment for a long time. Some
      aspects of their social interaction are described as communication in which
      members of both species influence each other's behaviour by special behaviour
      signals. Recent research is aimed at providing an evolutionary account for the
      emergence of communicative interactions between dogs and people. The present
      review summarizes how carefully applied experimental methods can be utilised to
      answer such research questions, in order to separate different processes that may
      underlie the mental abilities in dogs.

PMID- 19585262
TI  - Cystic echinococcosis in Europe and in Italy.
AB  - Cystic Echinococcosis remains a public health problem especially in the
      Mediterranean Region and the economic impact of Echinococcosis is great despite
      efforts to control it. In this review, an attempt is made to assess the present
      epidemiological situation of Echinococcosis in Europe and Italy.

PMID- 19585263
TI  - Innovations in seafood preservation and storage.
AB  - The increasing amount of farmed fish cannot be easily absorbed by the market as
      only fresh fish. The production and promotion of value-added fresh and processed
      fish products, which could fulfil consumers' present demands, may represent a
      solution to this problem. The aim of this paper is to review some of the most
      recent technologies, such as surface decontamination, use of "natural" additives
      and compounds, active packaging, used or experimented with to prolong shelf life,
      while ensuring the safety of fresh fish and fishery products.

PMID- 19585264
TI  - Mice with podocyte-specific overexpression of wild type alpha-actinin-4 are
      healthy controls for K256E-alpha-actinin-4 mutant transgenic mice.
AB  - Mutations in the gene ACTN4 encoding the actin bundling protein-alpha-actinin-4
      underlie an inherited form of kidney lesions known as focal segmental
      glomerulosclerosis (FSGS). Previously, we developed a model for this condition by
      generating mice with podocyte-specific overexpression of a disease-causing mutant
      alpha-actinin-4 (K256E-ACTN4 (pod+)). However, whether alpha-actinin-4
      overexpression artifacts and not the gain of affinity effects of the mutation
      accounted for the robust FSGS phenotype in these mice was unclear. To address
      this question, we developed a control line of mice with podocyte-specific
      overexpression of wildtype alpha-actinin-4 (wt-ACTN4 (pod+)). An 8.3 kb fragment
      of the mouse nephrin promoter (NPHS1) was used to drive expression of a
      hemagglutinin (HA)-tagged wildtype alpha-actinin-4 coding sequence in mice. Five
      founder lines expressing the HA-tagged alpha-actinin-4 protein in a podocyte
      specific manner were obtained, as determined by co-immunofluorescence with HA and
      synaptopodin antibodies. Quantitative PCR revealed that renal transgene mRNA
      levels of wt-ACTN4 (pod+) mice are similar to K256E-ACTN4 (pod+) mice. In
      contrast to K256E-ACTN4 (pod+) mice which exhibit albuminuria, podocyte foot
      process effacement and glomerular scarring, wt-ACTN4 (pod+) mice are healthy and
      indistinguishable from non-transgenic littermates. These findings suggest that
      the K256E mutation itself and not overexpression of alpha-actinin-4 protein per
      se accounts for the FSGS phenotype in our transgenic model.

PMID- 19585265
TI  - Seroprevalence of Toxoplasma gondii infection in breeding sows in Western Fujian
      Province, China.
AB  - The objective of the present investigation was to estimate the seroprevalence T.
      gondii infection in breeding sows in Western Fujian Province, the People's
      Republic of China. Sera collected from breeding sows during 2006-2007 from 6
      different regions in Western Fujian Province were assayed for antibodies to T.
      gondii by an indirect hemagglutination antibody (IHA) test. Antibodies to T.
      gondii were detected in 87 (14.38%) of 605 breeding sows. Differences in
      seroprevalence were observed between sampling regions, ranging from 10.14% to
      37.50%. The present investigation demonstrated that the prevalence of T. gondii
      infection in breeding sows in Fujian Province was high. Integrated control
      strategies and measures should be implemented to prevent and control T. gondii
      infection in breeding sows, which in turn will have significant implications for
      the control of human infection with T. gondii in this province.

PMID- 19585266
TI  - What governs the reaction center excitation wavelength of photosystems I and II?
AB  - The sun's spectrum harvested through photosynthesis is the primary source of
      energy for life on earth. Plants, green algae, and cyanobacteria-the major
      primary producers on earth-utilize reaction centers that operate at wavelengths
      of 680 and 700 nm. Why were these wavelengths "chosen" in evolution? This study
      analyzes the efficiency of light conversion into chemical energy as a function of
      hypothetical reaction center absorption wavelengths given the sun's spectrum and
      the overpotential cost associated with charge separation. Surprisingly, it is
      found here that when taking into account the empirical charge separation cost the
      range 680-720 nm maximizes the conversion efficiency. This suggests the
      possibility that the wavelengths of photosystem I and II were optimized at some
      point in their evolution for the maximal utilization of the sun's spectrum.

PMID- 19585267
TI  - Serum phenylalanine concentrations in patients post trauma and burn correlate to
      neopterin concentrations.

PMID- 19585269
TI  - Experience with the treatment of argininosuccinic aciduria during pregnancy.
AB  - We present the details of the management and the outcome of a pregnancy of a
      woman affected with argininosuccinic aciduria. Management with a closely
      monitored, protein-restricted diet, supplemented with L-arginine, resulted in the
      birth of a healthy infant boy and an uneventful perinatal course for the mother.

PMID- 19585268
TI  - Inherited disorders in the conversion of methionine to homocysteine.
AB  - During the last decade much important new information relating to the metabolic
      pathway from methionine to homocysteine has been gained. Interest has been
      stimulated by the discovery of two novel disorders, glycine N-methyltransferase
      deficiency and S-adenosylhomocysteine hydrolase deficiency. Another disorder in
      this pathway, methionine adenosyltransferase deficiency, has been increasingly
      detected, thanks to the expansion of newborn screening programmes by tandem mass
      spectrometry technology. These significant steps allow important insight into the
      pathogenesis of these three disorders, as well as into the mechanisms of damage
      to various organs (liver, brain, muscle) and point to the relevance of these
      disorders for crucial biological processes such as methylation, transsulfuration
      or carcinogenesis in mammals, the pathogenesis of numerous pathological
      conditions, in particular those associated with hyperhomocysteinaemia, the action
      and possible toxicity of some drugs or consequences of nutritional variations.
      This review summarizes current knowledge of three inherited disorders in this
      metabolic pathway and draws attention to their much broader significance for
      human health and understanding of important biological processes.

PMID- 19585270
TI  - Expression and characterization of Momordica Chanrantia anti-hyperglycaemic
      peptide in Escherichia coli.
AB  - A nucleic acid sequence MC, encoding Momordica Chanrantia anti-hyperglycaemic
      peptide MC6 (accession: AAX06814) synthesized according to Escherichia coli
      preferred codons, was cloned and expressed in E. coli. Recombinant protein pQE8
      MC (about 3.5 kDa) was purified and analyzed by 20% SDS-PAGE and western blot. It
      revealed that the expressed pQE8-MC had good solubility in aqueous media. An HPLC
      assay was used to confirm the expression of pQE8-MC. Subsequent pharmacological
      activity assay revealed a significant hypoglycemic effect of low dose treatments
      of pQE8-MC on male kunming mice. Four hours after an intravenous tail injection,
      the blood sugar levels of mice treated with pQE8-MC saline solution A3 (1 mg/kg
      BW) decreased greatly (P < 0.01) relative to the levels of a control group. This
      suggests that pQE8-MC, expressed in bioengineered E. coli, has a similar
      hypoglycemic function to the natural protein MC6 from M. Chanrantia. These
      results reveal the possibility of using bio-engineered bacteria as an anti
      diabetic agent.

PMID- 19585271
TI  - Identification of a null allele of cytochrome P450 3A7: CYP3A7 polymorphism in a
      Korean population.
AB  - Cytochrome P450 3A7 (CYP3A7) is expressed in the human fetal liver and plays a
      role in the metabolism of hormones, drugs, and toxic compounds. Genetic variants
      of CYP3A7 are associated with serum estrone level, bone density, and hepatic
      CYP3A activity in adults. We analyzed the genetic variations of CYP3A7 in a
      Korean population. From direct sequencing of all exons and flanking regions of
      the CYP3A7 gene in 48 Koreans, we found five genetic variants, including three
      novel variants. One variant, a thymidine insertion in exon 2 (4011insT), causes
      premature termination of CYP3A7 translation, which may result in a null
      phenotype. The novel variant was assigned to the CYP3A7*3 allele by the CYP
      allele nomenclature committee. For further screen of this novel variant in other
      ethnic populations, we used pyrosequencing to analyze an additional 185 Koreans,
      100 African Americans, 100 Caucasians, and 159 Vietnamese for the presence of
      this variant. The variant was not found in any other individuals, except for one
      Korean subject. The frequencies of two known functional alleles, CYP3A7*2 and
      CYP3A7*1C, were 26 and 0%, respectively, in Koreans. The frequencies of the
      functional CYP3A7 polymorphisms in Koreans were significantly different from
      those in Caucasians and African Americans. This is the first report of a null
      type allele of the CYP3A7 gene. It also provides population-level genetic data on
      CYP3A7 in Koreans to reveal the wide ethnic variation in CYP3A7 polymorphism.

PMID- 19585272
TI  - Molecular cloning and characterization of an up-regulated UDP-glucosyltransferase
      gene induced by DON from Triticum aestivum L. cv. Wangshuibai.
AB  - Fusarium head blight, also called scab, is a serious disease of small grain
      cereals and maize. Scab can not only cause yield loss, more seriously is that it
      can also deteriorate seed quality by contaminating the infected grains with
      trichothecenes toxins harmful to human and animal health. Deoxynivalenol (DON) is
      one of the most important toxin members. It was proposed that DON acted first as
      a virulence factor during fungal pathogenesis and then accumulated in grain to
      levels posing a threat to human and animal health. In the present research, by
      expression analysis of DON-induced samples using GeneChip Wheat Genome Array (
      http://www.affymetrix.com/products/arrays/specific/wheat.affx ), a DON-resistance
      related gene TaUGT3 (GenBank accession FJ236328) was cloned and characterized
      from a scab resistant wheat (Triticum aestivum L.) variety Wangshuibai. The full
      length cDNA of TaUGT3 was 1,755 bp and contained a putative open reading frame
      (ORF) with 496 amino acids encoding a UDP-glucosyltransferase (UGT). TaUGT3
      showed high similarity in amino acid level with DOGT1 gene in Arabidopsis, which
      is able to detoxify DON. TaUGT3 was located on the group 3 chromosomes of wheat
      using nulli-tetrasomic lines and deletion lines of Chinese Spring. Co-transformed
      of TaUGT3 with GFP genes to onion epidermis cells using transient transformation
      technique by microprojectile bombardment indicated the subcellular location of
      the protein encoded by TaUGT3 was in the plasma membrane and nuclear.
      Transformation and overexpression of the TaUGT3 gene in Arabidopsis could enhance
      tolerance against DON.

PMID- 19585273
TI  - The involvement of HSP22 from bay scallop Argopecten irradians in response to
      heavy metal stress.
AB  - Heat shock protein 22 (HSP22) is an important member of small heat shock protein
      (sHSP) subfamily which plays a key role in the process of protecting cells,
      facilitating the folding of nascent peptides, and responding to stress. In the
      present study, the cDNA of HSP22 was cloned from Argopecten irradians (designated
      as AiHSP22) by rapid amplification cDNA end (RACE) based on the expressed
      sequence tags (ESTs). The full-length cDNA of AiHSP22 was of 1,112 bp, with an
      open reading frame of 588 bp encoding a polypeptide of 195 amino acids. The
      deduced amino acid sequence of AiHSP22 showed high similarity to previously
      identified HSP22s. The expression patterns of AiHSP22 mRNA in different tissues
      and in haemocytes of scallops exposed to Cd(2+), Pb(2+) or Cu(2+) were
      investigated by real-time quantitative RT-PCR. The mRNA of AiHSP22 was
      constitutively expressed in all examined tissues, including haemocyte, muscle,
      kidney, gonad, gill and heart. The expression level in heart and muscle was
      higher than that in other tissues. The mRNA level of AiHSP22 in haemocytes was up
      regulated after a 10 days exposure of scallops to Cu(2+), Pb(2+) and Cd(2+).
      However, the expression of AiHSP22 did not increase linearly along with the rise
      of heavy metal concentration. Different concentrations of the same metal resulted
      in different effects on AiHSP22 expression. The sensitive response of AiHSP22 to
      Cu(2+), Pb(2+) and Cd(2+) stress indicated that it could be developed as an
      indicator of exposure to heavy metals for the pollution monitoring programs in
      aquatic environment.

PMID- 19585274
TI  - Expression of endostatin mediated by a novel non-viral delivery system inhibits
      human umbilical vein endothelial cells in vitro.
AB  - Ultrasound (US)-mediated microbubble destruction is recognized to have
      considerable potential for gene delivery, whereas, there is few report of its
      effect on enhancing liposomal transfection. In this study, we used pIRES2
      EGFP/hES containing human endostatin (hES) cDNA as target gene to test the
      hypothesis that US exposure with microbubbles could improve liposomal
      transfection, and to investigate the possibility of intracellular delivery of ES
      gene using this method. Under the controlled US exposure condition with
      microbubbles, the plasmid:liposome was transferred into COS-7 cells. The
      transfection rate, the expression of endostatin and the inhibition effect of
      transfection-endostatin on endothelial cells were assessed. The results revealed
      that US-mediated microbubble destruction together with liposome could
      significantly enhance gene transfection without obvious cell damage. By this
      means, endostatin gene could be efficiently transferred into COS-7 cells and
      expressed. The transfection-endostatin could inhibit endothelial proliferation
      and migration, which suggests that the non-viral method might be useful in anti
      angiogenesis therapy in the future.

PMID- 19585275
TI  - Chemical changes in aging Drosophila melanogaster.
AB  - The "Green Theory" of aging proposes that organismal lifespan is limited by the
      failure to repair molecular damage generated by a broad range of metabolic
      processes. Two specific predictions arise from this: (1) that these processes
      will produce a wide variety of stable but dysfunctional compounds that increase
      in concentration with age, and (2) that organisms maintained under conditions
      that extend lifespan will display a reduced rate of accumulation of such
      "molecular rubbish". To test these predictions, novel analytical techniques were
      developed to investigate the accumulation of damaged compounds in Drosophila
      melanogaster. Simple preparative techniques were developed to produce digests of
      whole D. melanogaster for use in three-dimensional (3D) fluorimetry and 1H NMR
      spectrometry. Cohorts of Drosophila maintained under normal conditions showed an
      age-related increase in signals consistent with damage whereas those maintained
      under conditions of low temperature and dietary restriction did not. 1H NMR
      revealed distinct age-associated spectral changes that will facilitate the
      identification of novel compounds that both increase and decrease during aging in
      this species. These findings are consistent with the predictions of the "Green
      Theory".

PMID- 19585276
TI  - Seizure detection with a commercially available bedside EEG monitor and the
      subhairline montage.
AB  - INTRODUCTION: Availability of standard, continuous electroencephalography (cEEG)
      monitoring in ICU is very limited, although commercially available 4-channel
      modules are present in many ICUs. We investigated the sensitivity of such modules
      compared with the more complete monitoring with a standard EEG system. METHODS:
      Seventy patients at high risk of seizures in the medical-surgical intensive care
      unit and Epilepsy Monitoring Unit were recorded simultaneously for at least 24 h
      with a 4-channel commercial ICU bedside monitoring system (Datex-Ohmeda) with a
      subhairline montage and a standard EEG machine (XLTEK) using the international 10
      20 system of electrode placement. Recordings were interpreted independently from
      each other. RESULTS: The 4-channel recordings demonstrated a sensitivity of 68
      and 98% specificity for seizure detection, and a sensitivity of 39% and a
      specificity of 92% for detection of spikes and PLEDs. CONCLUSIONS: The 4-channel
      EEG module has limited but practical usefulness for seizure detection when
      standard cEEG monitoring is not available.

PMID- 19585277
TI  - The longitudinal profile of bilirubin and ferritin in the cerebrospinal fluid
      following a subarachnoid hemorrhage: diagnostic implications.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) spectrophotometry for bilirubin is a highly
      sensitive test in the diagnostic work up of a suspected subarachnoid hemorrhage
      (SAH). CASES: We report two cases suffering from an aneurysmal SAH in which
      extraventricular drainage for acute hydrocephalus was required. Longitudinal
      analyses of the CSF samples demonstrated that CSF bilirubin was detectable in all
      cases during the first week, becoming undetectable in one case in the second
      week. Importantly, CSF ferritin levels rose substantially (>1,000 ng/ml) after 6
      days, peaking around 3,000 ng/ml after 2 weeks (normal upper reference range 12
      ng/ml). In both cases blood was visible on the initial CT brain scan,
      disappearing on a later scan. CONCLUSION: CSF ferritin levels may be an important
      additional laboratory test in the diagnostic work-up of patients with a suspected
      SAH. CSF ferritin levels may prove particularly helpful in cases with late
      presentation if the CT brain scan is normal and CSF bilirubin level is
      undetectable.

PMID- 19585278
TI  - Blockage of reuniting duct in Meniere's disease.
AB  - CONCLUSION: The bony saccular orifice to the bony groove of the ductus reuniens
      (reuniting duct) could not be visualized in the Meniere's ear with significantly
      greater frequency compared with normal subjects, which suggests that the
      reuniting duct is affected by radio-opaque substances in CT findings. OBJECTIVE:
      This study investigated a more specific, objective, and simpler strategy to
      diagnose Meniere's disease by assessing the reuniting duct. SUBJECTS AND METHODS:
      We examined the ears of 12 patients with definitely diagnosed unilateral
      Meniere's disease in stage 3 based on Meniere's disease criteria proposed by the
      Committee on Hearing and Equilibrium of the American Academy of Otolaryngology
      Head and Neck Surgery (AAO-HNS), and the ears of 12 normal control subjects using
      three-dimensional (3D) cone beam CT. RESULTS: The bony groove of the reuniting
      duct between the saccule and cochlea was visualized in all control subjects.
      However, the bony saccular orifice to the bony groove could not be visualized in
      the lesional ear of Meniere's patients with significantly greater frequency
      compared with those of the contralateral non-lesional ears and control ears (p <
      0.01). This orifice was not patent in 66.7% (8 of 12 ears) on the lesional side
      but all contralateral non-lesional ears of the patients and normal control ears
      were patent.

PMID- 19585288
TI  - The cost of relapse in schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: The aim of this study was to quantify the costs and resource
      utilization associated with a relapse of schizophrenia or schizoaffective
      disorder. METHODS: The study comprised a retrospective audit of data from 200
      patients diagnosed with schizophrenia or schizoaffective disorder who were
      admitted to hospital for a relapse of their disorder in two mental health
      services in Australia between 1 June 2001 and 31 May 2002. Resource use and
      costing data were collected for 12 months before and 12 months after the
      hospitalization. RESULTS: There was an increase in contacts per month and
      associated outpatient costs after the index admission which persisted for the
      full 12 month data collection period (total of AUD $637). There was also a total
      increase in hospital costs but this did not persist beyond the first 2 months of
      the follow-up period and is likely explained by the index admission. CONCLUSIONS:
      Increased healthcare resource utilization and costs results from relapse in
      patients with schizophrenia or schizoaffective disorder. An increase in service
      use and costs persist for a considerable time period after an episode of relapse.

PMID- 19585289
TI  - Community treatment orders and competence to consent.
AB  - OBJECTIVE: The aim of this paper is to explore the relationship between civil
      commitment under a Community Treatment Order (CTO) and competence to consent to
      treatment. METHOD: A purposive convenience sample of 10 service users under CTOs
      were interviewed using the MacArthur Competence Assessment Tool for Treatment
      (MacCAT-T). Ratings were compared with the ratings of 10 matched voluntary
      service users. RESULTS: Seventy percent of the CTO sample were found to be
      incompetent according to the MacCAT-T, compared to 20% of the comparison group (p
      = 0.004). The proportion of the CTO sample found to be incompetent reduces to 50%
      if the subscale of appreciation is excluded (p = 0.004). Most people in each
      group would elect to continue their current treatment if given the choice.
      CONCLUSION: Findings of this study suggest that mental health law reform
      introducing considerations of competence could lead to a substantially different
      group of people being subject to CTOs. If the CTO is carefully targeted and not
      used excessively, it is likely to be accorded qualified acceptance for most
      service users for whom it is used.

PMID- 19585290
TI  - Patients who do well and who do less well in an inpatient adolescent unit.
AB  - OBJECTIVE: The primary aim of the study was to investigate whether patient
      characteristics such as age, sex, length of inpatient stay and reason for
      admission were related to positive or negative treatment outcome at an adolescent
      inpatient unit. METHOD: This study employed a prospective cohort design in the
      form of a clinical audit. Health of the Nation Outcome Scales for Children and
      Adolescents (HoNOSCA) pre- and post-admission scores were compared for the whole
      sample and across diagnoses. RESULTS: While there was a significant reduction
      overall in symptoms following an inpatient stay, patient characteristics and
      reason for admission were not related to outcomes at a statistically significant
      level. CONCLUSIONS: This inpatient unit generally functions as a short stay unit
      and as a result it is difficult to draw any meaningful conclusions as to what
      sort of patient would benefit most from an admission to the unit.

PMID- 19585291
TI  - Children as consumer participants of child and adolescent mental health services.
AB  - OBJECTIVE: This pilot study explored children's perspectives of an initial
      assessment at outpatient child and adolescent mental health services (CAMHS).
      METHOD: A semi-structured qualitative interview was undertaken with nine children
      aged 7-12 years. Transcribed interviews were analyzed to reveal common themes.
      RESULTS: Children generally coped well with the interview. They identified themes
      involving stigma, qualities and approaches of staff, aspects of the CAMHS
      environment, and anxiety about attending CAMHS as key issues. CONCLUSIONS: This
      pilot study suggests that it is feasible to interview children regarding their
      perspectives on attending a CAMHS. Children's views of CAMHS are required to help
      inform developmentally appropriate service delivery.

PMID- 19585292
TI  - An evaluation of monitoring practices in patients on second generation
      antipsychotics.
AB  - OBJECTIVE: Treatment with second generation antipsychotics (SGAs) can increase
      the risk of patients with schizophrenia developing obesity, hyperlipidaemia and
      diabetes. Routine monitoring is recommended, but clinical practice suggests
      monitoring is not conducted at a rate necessary for these comorbidities. The aim
      was to audit what proportion of patients were having their weight, height, girth,
      body mass index, lipids and blood sugar levels monitored and recorded. METHOD: An
      audit of patients with schizophrenia, discharged from three psychiatric wards,
      was conducted. Two data sheets were recorded for every patient and inter-rater
      reliability was calculated. Data were then entered into SPSS and statistical
      significance calculated. RESULTS: The sample consisted of 93 patients; SGAs were
      taken by 31% of admitted and 88% of discharged patients. Of these, 65% had their
      weight recorded, 61% height, 31% random blood sugar levels, 3% postprandial blood
      sugar levels, 2% glycosylated haemoglobin, and 7.5% cholesterol and
      triglycerides. Girth and BMI were not recorded. Abnormalities were detected in
      29% of recorded BSL and 2% of recorded cholesterol. CONCLUSIONS: Patients with
      schizophrenia on antipsychotics have an alarmingly low rate of monitoring of
      these common adverse effects and comorbidities. Clinicians need to be aware of
      this, so that they can improve their practice.

PMID- 19585293
TI  - Alprazolam prescribing in Tasmania: a two-fold intervention designed to reduce
      inappropriate prescribing and concomitant opiate prescription.
AB  - OBJECTIVE: The population rate of alprazolam prescribing in Tasmania has been
      more than double that of national rates. Serious adverse events have been
      observed through co-administration of opioid medications with alprazolam. A two
      fold intervention, comprising GP education coupled with changes to prescribing
      regulations, was designed with the intention to decrease inappropriate
      prescribing of alprazolam and thereby reduce adverse outcomes. The aim of this
      study was to assess the impact of the intervention on prescribing rates. METHOD:
      We measured the number of alprazolam prescriptions for the years prior to and the
      year following the intervention. Health Insurance Commission data were utilized
      to enable comparison of subsidized prescription rates for alprazolam in Tasmania,
      and compared with national data. Participants were registered medical
      practitioners in Tasmania who were potential prescribers of alprazolam. The
      interventions were three GP Education Meetings during June 2007, one in each of
      the major regions of Tasmania, regarding evidence-based interventions for panic
      disorder. Changes to regulatory procedures to minimize co-prescription of
      alprazolam with opioids was implemented in September 2007. RESULTS: A reduction
      in alprazolam prescribing in Tasmania occurred after the interventions.
      CONCLUSION: Education can be an effective strategy to influence prescribing
      behaviour of doctors. It is likely that this effect can be augmented by adoption
      of more stringent regulatory requirements.

PMID- 19585294
TI  - The University of Western Australia Institute of Psychiatry for Medical Students:
      an Australian first.
AB  - OBJECTIVE: Recruitment of medical graduates into psychiatry has become a growing
      issue over the last few decades. This paper describes the implementation of an
      innovative program, based on a Canadian concept, that aimed to promote psychiatry
      as a career choice to medical students, to immerse them in the 'world of
      psychiatry', and introduce them to potential mentors. The University of Western
      Australia Institute of Psychiatry for Medical Students was a week-long program
      that provided medical students with an opportunity to participate in a diverse
      agenda of interactive seminars on a range of psychiatric subspecialties and the
      neurosciences. Students were also able to attend elective sessions and meet
      registrars and psychiatrists on an informal basis. Lunches and social events were
      also provided. CONCLUSION: Twenty-one students attended the inaugural Institute.
      Twenty-seven speakers contributed to the morning seminars and there were 17
      clinical elective site visits. Feedback from students was positive and the week
      was rated highly, both in terms of its organization and from an academic
      perspective. It is planned to run the Institute annually and, in time, it is
      hoped that it will increase the numbers of students who choose psychiatry as a
      career option.

PMID- 19585295
TI  - Medical students' attitudes towards a career in psychiatry before and after
      viewing a promotional DVD.
AB  - OBJECTIVES: The objectives were, first, to determine attitudes towards psychiatry
      as a career among medical students currently enrolled at the University of Sydney
      and, second, to establish the immediate impact on those attitudes of a
      promotional DVD, released by the Royal Australian and New Zealand College of
      Psychiatrists. METHOD: Medical students enrolled in the University of Sydney in
      2008 were invited to complete a voluntary online questionnaire, in which their
      attitudes towards psychiatry were explored, and the immediate effects of a 15
      minute DVD were ascertained. RESULTS: A total of 123 students participated. Only
      one student identified psychiatry as their chosen career. Medical students viewed
      psychiatry as the least attractive specialty for the degree to which patients are
      helped effectively and in terms of having a reliable scientific foundation.
      However, it rated well in regard to being intellectually challenging, a rapidly
      advancing field of medicine, and providing research opportunities and a good
      lifestyle. Psychiatry is less respected than most other specialties by students
      and they perceive this discipline to be poorly respected by other medical
      students and current medical practitioners. After viewing the DVD, there were
      improved student ratings of the benefits of a career in psychiatry, especially in
      relation to the specialty being enjoyable, offering effective treatment and
      having a scientific foundation. There was also enhanced understanding of the role
      of a psychiatrist in just over half of the participants and increased interest in
      psychiatry in about 30% of participants. The DVD was most effective in increasing
      awareness of the diversity of subspecialties available within psychiatry, good
      lifestyle factors, and the training involved. CONCLUSION: Among medical students,
      psychiatry is perceived as unattractive and fails to command the respect afforded
      other specialties. The viewing of a promotional DVD by medical students was found
      to be effective in improving their attitudes towards psychiatry and increasing
      their interest in pursuing a career in the specialty. However, the long-term
      impact of this modest improvement is unknown and the low survey response rate
      limits the extent to which the results can be generalized.

PMID- 19585296
TI  - Soaring on the wings of the wind: Freud, Jews and Judaism.
AB  - OBJECTIVES: This paper looks at Freud's Jewish identity in the context of the
      Jewish experience in Eastern and Central Europe after 1800, using his family
      history and significant figures in his life as illustration. Sigmund Freud's life
      as a Jew is deeply paradoxical, if not enigmatic. He mixed almost exclusively
      with Jews while living all his life in an anti-Semitic environment. Yet he
      eschewed Jewish ritual, referred to himself as a godless Jew and sought to make
      his movement acceptable to gentiles. At the end of his life, dismayed by the
      rising forces of nationalism, he accepted that he was in his heart a Jew "in
      spite of all efforts to be unprejudiced and impartial". The 18th century Haskalla
      (Jewish Enlightenment) was a form of rebellion against conformity and a means of
      escape from shtetl life. In this intense, entirely inward means of intellectual
      escape and revolt against authority, strongly tinged with sexual morality, we see
      the same tensions that were to manifest in the publication by a middle-aged
      Viennese neurologist of a truly revolutionary book to herald the new 20th
      century: The Interpretation of Dreams. Freud's life and work needs to be
      understood in the context of fin-de-siecle Vienna. Mitteleuropa, the cultural
      renaissance of Central Europe, resulted from the emancipation and urbanization of
      the burgeoning Jewish middle class, who adopted to the cosmopolitan environment
      more successfully than any other group. In this there is an extreme paradox: the
      Jewish success in Vienna was a tragedy of success. CONCLUSIONS: Freud, despite a
      deliberate attempt to play down his Jewish origins to deflect anti-Semitic
      attacks, is the most representative Jew of his time and his thinking and work
      represents the finest manifestation of the Litvak mentality.

PMID- 19585297
TI  - The cover art of Australasian Psychiatry: in brief conversation with John
      Dickson. [Interview by Garry Walter and Harry Minas].

PMID- 19585299
TI  - Audit of antipsychotic polypharmacy in Christchurch.

PMID- 19585300
TI  - Dangerousness and risk assessment.

PMID- 19585301
TI  - An unusual case of hospital-acquired infection: Legionella Longbeachae.

PMID- 19585308
TI  - Effect of granule size on the interference colors of starch in polarized light.
AB  - A Nikitin-Berek compensator tilted at 5.5 degrees in a polarizing microscope was
      used to create a background second-order blue interference color against which
      starch granules were examined. A grating monochromator showed the first
      interference minimum of the background was at 590 nm. Starch granules have a
      radial molecular structure. Thus, some radii were in line with the axis of the
      compensator while others were across the compensator axis. Where radial
      birefringence counteracted the background birefringence, starch granules had two
      quadrants with a bright yellow first-order interference color. Where radial
      birefringence added to the background birefringence, there were two quadrants of
      second-order blue (higher than the background). In yellow quadrants where
      birefringence was reduced, the wavelength of the first interference minimum was
      reduced. In blue quadrants where birefringence was increased, the wavelength of
      the first interference minimum was increased. The extent to which the
      interference minimum of the background birefringence was shifted by starch
      granules was strongly dependent on the size of the starch granules. For yellow
      quadrants, the shifts were: r = -0.87, P < 0.001, n = 22 for corn starch; r = -
      0.94, P <0.001, n = 22 for tapioca starch; and r = -0.94, P <0.001, n = 12 for
      potato starch. For blue quadrants, the shifts were: r = 0.80, P < 0.001, n = 22
      for corn; r = 0.81, P < 0.001, n = 22 for tapioca; and r = 0.93, P < 0.001, n =
      16 for potato. When interference colors are used to evaluate starch granules, the
      granules should be similar in size or a correction must be made for granule size,
      and the Michel-Levy chart of interference colors may be used to collect data
      subjectively.

PMID- 19585302
TI  - Rehabilitating ECT's public image.

PMID- 19585309
TI  - The effect of stuttering on communication: a preliminary investigation.
AB  - This paper describes a study in which Systemic Functional Linguistics was applied
      to describe how people who stutter use language. The aim of the study was to
      determine and describe any differences in language use between a group of 10
      adults who stutter and 10 matched normally-fluent speakers. In addition to formal
      linguistic analyses, analyses drawn from Systemic Functional Linguistics were
      used to further investigate the expression of both syntactic and semantic
      complexity. The findings from this study replicated previous findings of Packman
      et al. in which they found that the language used by people who stutter was
      significantly less complex than the control group. Another major finding was that
      adults who stuttered used the linguistic resource of modality significantly less
      than the normally-fluent matched peers. The implications these strategies have on
      communication and social participation will be discussed.

PMID- 19585310
TI  - How do children ascribe gender to nouns? A study of Spanish-speaking children
      with and without specific language impairment.
AB  - The purpose of this investigation was to identify how Spanish-speaking preschool
      children with and without specific language impairment (SLI) use the various cues
      available for ascribing a noun's inherent gender in the language. Via an invented
      word task, four types of cues were isolated and presented to each child: (1) two
      types of noun-internal cues (semantic transparency and word ending), and (2) two
      types of noun-external cues (article gender and adjective gender). Eleven
      children with typical language skills, 11 children with SLI, and 11 adults
      participated in the study. Results indicated, as expected, that adults
      outperformed both child groups. Significant differences were observed in the
      children's use of article cues, with the typical children outperforming the
      children with SLI. Individual data also indicate that most children with SLI were
      using the noun-internal cue of word ending effectively. Discussion of previous
      research in the area of gender agreement in Spanish-speaking children with SLI
      and explanations of potential reasons for the children's performance are
      addressed.

PMID- 19585311
TI  - A comparison between written and spoken narratives in aphasia.
AB  - The aim of the present study was to explore how a personal narrative told by a
      group of eight persons with aphasia differed between written and spoken language,
      and to compare this with findings from 10 participants in a reference group. The
      stories were analysed through holistic assessments made by 60 participants
      without experience of aphasia and through measurement of lexical and syntactic
      variables. The findings showed that the participants with aphasia generally
      received lower ratings than the reference group, but also that stories written by
      participants with aphasia were rated as easier to understand, more interesting,
      and more coherent than the group's spoken stories. Regression analysis showed
      that syntax could predict several of the rated variables for the stories told by
      the participants with aphasia. Results point to the need to include writing
      training in language rehabilitation in order to increase the ability for persons
      with aphasia to participate in communicative situations in everyday life.

PMID- 19585312
TI  - The production of linguistic prosody in subjects with aphasia.
AB  - This study investigated the production of linguistic prosody in subjects with
      left hemisphere damage (LHD). Three experiments involving the production of
      lexical stress in nouns vs verbs, compound nouns vs tag constructions, and echo
      questions vs statements were conducted. Acoustic measurements (fundamental
      frequency (F(0)), duration and amplitude) of the prosodic structures were
      examined and naive listeners were asked to identify the meanings of the
      utterances. The results of the acoustic measurements indicated that LHD subjects
      did not produce prosodic structures that were comparable to control subjects to
      convey different linguistic meanings in all three experiments. Naive listeners
      had greater difficulty identifying the intended meanings of the utterances
      produced by the LHD subjects than control subjects in all three experiments. The
      results suggest that the left hemisphere plays a role in the production of
      linguistic prosody.

PMID- 19585317
TI  - Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils
      oxidative burst and nitric oxide production after exercise.
AB  - Seventeen volunteer male professional cyclists were randomly assigned to control
      or supplemented (6 g L-citrulline-malate) groups and participated in a cycling
      stage. Blood samples were taken in basal conditions, after the race and 3 h post
      race. Citrulline supplementation significantly increased plasma concentration of
      both arginine and citrulline after the stage only in the supplemented group.
      Polymorphonuclear neutrophils (PMNs) from controls responded to exercise with a
      progressive decrease in ROS production. Supplemented PMNs significantly increased
      ROS production after exercise compared to basal values and diminished to values
      lower than basal at recovery. PMN nitrite concentration was significantly higher
      after exercise and recovery only in the supplemented group. Markers of oxidative
      damage-CK, LDH, malondialdehyde-and DNA damage remained unchanged in both groups.
      In conclusion, oral L-citrulline administration previous to a cycling stage
      increases plasma arginine availability for NO synthesis and PMNs priming for
      oxidative burst without oxidative damage.

PMID- 19585318
TI  - Antioxidant activities of extracts and subfractions from Inonotus Obliquus.
AB  - The ethanolic crude extracts and three subfractions (ethyl acetate fraction, n
      butanol fraction, and aqueous fraction) from Inonotus Obliquus were obtained by
      sequential partitioning and their antioxidant activities were investigated in the
      present study. The methods of the total antioxidant capacity measured by the
      ferric-reducing antioxidant power assay, reducing power assay, scavenging
      activities towards DPPH, superoxide anion and hydroxyl radical employed in this
      study were established in in vitro systems. The amounts of total phenolics and
      total flavonoids were also determined by spectrophotometer. The results showed
      that the crude extracts and subfractions exhibited antioxidant activities in
      different evaluating system. The decreasing order of antioxidant activities is
      ethyl acetate fraction >n-butanol fraction >crude extract>aqueous fraction. A
      similar order of the amounts of phenolics and flavonoids in extract and
      subfractions was found. The results showed that the extent of antioxidant
      activities is in accordance with the amounts of phenolics and flavonoids existing
      in extracts and subfractions.

PMID- 19585319
TI  - Hair structures are effectively altered during 810 nm diode laser hair epilation
      at low fluences.
AB  - BACKGROUND: Diode lasers with high fluence and cooling technology are effective
      at removing unwanted hair but are also associated with discomfort and morbidity,
      especially when treating dark or tanned skins. METHODS: Thirty patients with skin
      phototypes IV and V (range: 23-62 years of age; average: 39 years) underwent a
      single hair removal treatment using a new diode laser (810 nm) technology that
      incorporates low fluence but very high average power. The treatment technique
      employed multiple, in-motion, repetitive laser passes on a 100 cm(2) area of the
      skin. A 5mm punch biopsy was carried out before and after a single treatment.
      Tissue samples were harvested and stained with haematoxylin-eosin. RESULTS: The
      physical integrity of hair follicles was altered with inflammatory infiltrate,
      hair shaft detachment from its sheath, and perifollicular oedema, related to
      incipient necrosis. CONCLUSION: Low fluence but high average power diode laser
      technology yields significant changes in hair structure and architecture in
      patients with dark skin types. The procedure caused low levels of discomfort and
      was well tolerated.

PMID- 19585321
TI  - Social work with older immigrants & their families. Foreword.

PMID- 19585322
TI  - Experiences of aging among immigrants from India to the United States: social
      work practice in a global context.
AB  - The aging of immigrants is a critical component in the health dynamics of the
      nation's aging population. To date, few studies have addressed within-group
      diversity and linked contemporary contexts of global connectedness with the aging
      experiences of older immigrants. This study aims to conceptually understand the
      diversity in aging dynamics within a specific immigrant group: Indian immigrants
      in New York City. The impact of globalization and transnational connection on
      aging experiences on 2 within groups-Indians who came to the United States at age
      of 65 or older (LLIs) and those who came at an early age (ELIs) are analyzed.
      Implications for social work practice, research and policy are discussed.

PMID- 19585320
TI  - Dermatological patient safety: problems and solutions.
AB  - BACKGROUND: Patient safety issues are the forefront of delivering effective
      quality healthcare. The fast pace and high volume of dermatology practice
      presents an opportunity for new research on error prevention and patient safety.
      OBJECTIVE: To identify areas of concern in patient safety to introduce starting
      points for new improvement projects in dermatology. METHODS: Aliterature search
      was performed using the PubMed database with the search terms 'patient safety'
      and 'quality of care'. The articles were categorized into three topics concerning
      patient safety research: safety in treatment and procedures received; safety
      issues related to facility infrastructure; and human resource management.
      RESULTS: Many issues identified as healthcare shortcomings such as wrong site
      surgery, patient misidentification, specimen errors, medication errors,
      communication failure, poor teamwork, healthcare worker management defects, and
      facility safety design problems were discussed in the literature. Each of these
      requires exploration with new safety initiatives for resolution. Alimitation
      included omitting pieces on occupational health and safety that could contribute
      to overall patient safety. Our search also included only data from one database.
      CONCLUSIONS: Patient safety is an ever-evolving process requiring continuous
      attention by practicing physicians including dermatologists, healthcare staff,
      patients, and research scholars to discover and implement new safety initiatives
      for overall healthcare improvement.

PMID- 19585323
TI  - Financial abuse in elderly Korean immigrants: mixed analysis of the role of
      culture on perception and help-seeking intention.
AB  - This study aims to evaluate how elderly Korean immigrants perceive and respond to
      a hypothetical incident of financial abuse on the basis of their cultural
      background. By using a quota sampling strategy, 124 elderly Korean immigrants
      were recruited. A mixed-method approach was employed to explore the role of
      culture on elderly immigrants' view of financial abuse and the construct of
      independent and interdependent self-construal was adopted to theoretically guide
      the study. Mixed-method analysis confirmed considerable influence of culture,
      particularly in responding to the abusive situation. Although the vast majority
      of the elders (92%) perceived financial abuse as elder mistreatment, only two
      thirds (64%) intended to seek help. Five major themes for not seeking help were
      produced. These are: (a) issues related to family problems, (b) tolerance of the
      abuse, (c) shame, (d) victim blame, and (e) mistrust toward third party
      intervention. A series of binary logistic regressions revealed (a) a lower
      likelihood of seeking formal types of help with those who had higher level of
      adherence to traditional values and (b) the profile of vulnerable elderly Koreans
      who are at higher risk of being financially abused: male and less educated. This
      article also discusses implications for social work practice and elder
      mistreatment policy, particularly focusing on how to work with elderly Korean
      immigrants who are vulnerable to this problem and who tend to use collectivistic
      cultural values in responding to financial abuse.

PMID- 19585324
TI  - Ethnic enclave resources and predictors of depression among Arizona's Korean
      immigrant elders.
AB  - This is the first study examining predictors of depression among Arizona's Korean
      immigrant elders not residing in ethnic enclaves. A snowball sample of 120
      elders, aged 64 and over, completed the study interview. The proportion of
      respondents reporting depression was 38.1%, higher than the incidence reported
      among counterparts in New York City's immigrant ethnic enclaves. Multiple
      regression analyses (R2=.44) indicate that English language proficiency had the
      most powerful effect on explaining depression. Discussion centers on why programs
      aimed at reducing language barriers among socially isolated immigrant elders need
      to be a first priority in service provision.

PMID- 19585325
TI  - How older Hispanic immigrants in New York City cope with current traumatic
      stressors: practice implications.
AB  - Older minority immigrant groups in the United States may be at increased risk for
      traumatic stress in an age of terrorism and of civil and political unrest. This
      exploratory study investigated how older Hispanic immigrants in New York City
      coped in response to current traumatic stressors, and whether they differed from
      a comparison group of older US-born non-Hispanics. We administered the Impact of
      Events Scale-Revised (IES-R) and the Brief COPE instruments to 24 older Hispanic
      immigrants and 15 older non-Hispanics, born in the United States, at 2 senior
      centers. Hispanic immigrants showed greater symptomatic response to current
      stressors as measured by significantly higher scores on the hyperarousal and
      avoidance subscales of the IES-R. Both groups used passive coping strategies.
      Older Hispanic immigrants may be at increased risk for negative psychological
      consequences caused by a current stressor. Practitioners should encourage older
      Hispanic immigrants to use active coping strategies to deal with those stressors.

PMID- 19585326
TI  - Religious/spiritual and other adaptive coping strategies among Chinese American
      older immigrants.
AB  - Although recent scholarship focuses on the importance of religion to ethnic
      minorities and immigrants, relatively little attention has been given to how
      faith and spirituality help Asian immigrant elderly cope with life's challenges.
      This exploratory study was undertaken via in-depth interviews with 12 Chinese
      American older adults to further explore the meaning of suffering and faith as a
      coping mechanism for these challenges. Findings reveal that these respondents
      have developed particular adaptive strategies in managing their life challenges
      incorporating socio-emotional, cognitive, and instrumental aspects.
      Religious/spiritual coping was found to be embedded with respondents' values,
      faith, and cultural beliefs, and seem to be an important factor in developing
      effective coping strategies. Implications for the importance of culturally
      sensitive social work practice are discussed.

PMID- 19585327
TI  - Intergenerational support of Chinese rural elders with migrant children: do sons'
      or daughters' migrations make a difference?
AB  - This article investigates how the out-migration of adult children affects
      monetary, instrumental, and emotional support of Chinese rural elders over a 5
      year interval, and whether the gender of migrant children makes a difference in
      such relationships. With a sample of 1,006 older parents (60+) in rural Anhui
      province, the result of hierarchical regression analyses showed that support from
      adult children was mainly needs based. Declining income of older parents related
      to increased monetary support. Experiencing widowhood and difficulties with
      instrumental activities of daily living was associated with higher probability of
      receiving instrumental support. Beyond expanding parental needs, only the out
      migration of sons led to more monetary and emotional support among elders over
      time. Implications for policy, social work practice, and future research are
      discussed.

PMID- 19585328
TI  - Avenues and barriers to access of services for immigrant elders: state and local
      policies for OAA units on aging.
AB  - The diversification and aging of the US population has been at the root of many
      political and policy debates in recent years. Of particular interest has been the
      place of immigrants in an aging society, and what rights these immigrants are
      entitled to. The objective of this article is to describe the current avenues and
      barriers to access of services for immigrant elders and examine potential
      solutions for reform. The article begins with a historical overview of the policy
      issue, followed by the current status of the issue in the United States and
      suggestions for reform.

PMID- 19585330
TI  - Ergonomics. Case study: safety training issues for Hispanic construction workers.

PMID- 19585331
TI  - Indoor allergens in Minnesota schools and child care centers.
AB  - Elevated concentrations of allergens in the indoor environment may cause allergic
      sensitization and symptoms. Occupant exposure to indoor allergens in educational
      facilities should and can be controlled. This study (1) assessed the presence of
      indoor allergens in Minnesota schools and child care centers, (2) characterized
      the distribution of allergens in different materials, and (3) evaluated the
      effect of building and maintenance interventions on allergen concentrations.
      Settled dust samples were collected from carpet, vinyl tile floors, and
      upholstered furniture in six schools and seven child care centers before and
      after interventions. Interventions included changes to cleaning, ventilation,
      entry mats, furnishings, flooring, and classroom items. The amount of total dust,
      culturable fungi, and indoor allergens--cockroach, dust mite, cat, and dog--were
      quantified in the dust samples. Cockroach and dust mite allergens were generally
      low and below the detection limit, but one dust mite allergen was detected in
      some areas. Cat and dog allergens were frequently detected at elevated levels,
      with half the samples above the provisional sensitization risk thresholds and a
      few samples above the symptom thresholds. Allergen concentrations were highest in
      upholstered furniture, followed by carpeting and then vinyl floor tile. Cat and
      dog allergens were lower after the interventions. Cat and dog allergens, but not
      dust mite and cockroach allergens, seem to be ubiquitous in child care and
      elementary schools of the U.S. Midwest. These allergens may contribute to
      sensitization in atopic individuals and occasionally cause symptoms in sensitized
      allergic individuals. Fleecy materials that are not adequately cleaned, such as
      upholstered furniture, appear to be the most significant allergen reservoirs.
      Modest environmental interventions can be implemented by building staff, which
      should result in lower allergen concentrations.

PMID- 19585332
TI  - Taking the measure of dissociation.

PMID- 19585333
TI  - Evidence of dissociative amnesia in science and literature: culture-bound
      approaches to trauma in Pope, Poliakoff, Parker, Boynes, and Hudson (2007).
AB  - The current culture of traumatic stress studies includes research that identifies
      the ways in which stress and trauma impair learning and memory in both humans and
      animals. Yet it also contains health professionals who argue that individuals
      cannot forget traumatic events. Many accounts present differences among these
      positions as a legitimate debate despite the substantial forensic, survey, and
      neurological evidence that both demonstrates the capacity for people to exhibit
      impaired memory for trauma and highlights specific mechanisms. In a recent
      article, H. G. Pope, M. B. Poliakoff, M. P. Parker, M. Boynes, and J. I. Hudson
      (2007) hypothesized that if individuals could forget trauma, the phenomenon would
      appear in world literature prior to 1800. They conducted a contest to generate
      submissions of examples and determined that dissociative amnesia is a culture
      bound syndrome. Their report fails to provide a thorough account of all
      submissions and the process through which they were all rejected, offers highly
      questionable literary analyses, and includes several misrepresentations of the
      state of the science regarding memory for trauma. This response addresses
      methodological problems with the contest, explores examples of forgetting trauma
      from literature written before 1800, examines social and historical aspects of
      the issue, and summarizes the extensive cognitive and neurological data that Pope
      et al. did not consider. The present article conceptualizes the premise of the
      contest and the authors' conclusion as symptomatic of a culture affected by
      biases that include the denial of trauma and its effects.

PMID- 19585336
TI  - A preliminary study examining relationships between childhood maltreatment,
      dissociation, and self-injury in psychiatric outpatients.
AB  - This study aimed to examine the relationships between childhood maltreatment,
      dissociation, and self-injury. Unlike much previous research, this study included
      5 different types of childhood maltreatment in addition to sexual and physical
      abuse, and it looked at parameters of maltreatment such as onset and duration.
      Participants (n = 58) were psychiatric outpatients. The different types of
      maltreatment co-occurred, with most participants suffering 4 or all 5 types. It
      was found that childhood maltreatment rather than dissociation predicted self
      injury. Furthermore, physical abuse rather than the other kinds of childhood
      maltreatment was significantly related to self-injury.

PMID- 19585337
TI  - Affective responsiveness, betrayal, and childhood abuse.
AB  - Several trauma-specific and emotion theories suggest that alterations in
      children's typical affective responses may serve an attachment function in the
      context of abuse by a caregiver or close other. For example, inhibiting negative
      emotional responses or expressions might help the child preserve a relationship
      with an abusive caregiver. Past research in this area has relied on self-report
      methods to discover links between affective responsiveness and caregiver abuse.
      Extending this literature, the current study used facial electromyography to
      assess affective responsiveness with 2 measures: mimicry of emotional facial
      expressions and affective modulation of startle. We predicted that women who
      reported childhood abuse by close others would show alterations in affective
      responsiveness relative to their peers. We tested 100 undergraduate women who
      reported histories of (a) childhood sexual or physical abuse by someone close,
      such as a parent (high-betrayal); (b) childhood abuse by someone not close (low
      betrayal); or (c) no abuse in childhood (no-abuse). Especially when viewing
      women's emotional expressions, the high-betrayal group showed more mimicry of
      happy and less mimicry of angry faces relative to women who reported no- or low
      betrayal abuse, who showed the opposite pattern. Furthermore, women who reported
      high-betrayal abuse showed less affective modulation of startle during pictures
      depicting men threatening women than did the other two groups. Findings suggest
      that, as predicted by betrayal trauma theory, women who have experienced high
      betrayal abuse show alterations in automatic emotional processes consistent with
      caregiving-maintenance goals in an abusive environment.

PMID- 19585338
TI  - Narratives of dissociation: insights into the treatment of dissociation in
      individuals who were sexually abused as children.
AB  - This article provides an in-depth understanding of the treatment of dissociation
      from the perspective of 7 individuals who have a history of childhood sexual
      abuse and engage in moderate to high levels of dissociative behavior. Levels of
      dissociation were screened using the Dissociative Experiences Scale (E. Bernstein
      Carlson & F. Putnam, 1993), and individual interviews were conducted to gain
      insight into how dissociation can best be treated in a therapeutic context. From
      a narrative research design with a holistic-content analysis (A. Lieblich, R.
      Tuval-Mashiach, & T. Zilber, 1998), 3 major themes and 16 subthemes were
      revealed. The major themes included (a) identifying specific tools and techniques
      that were recognized as critical in managing dissociative symptoms, (b)
      challenging the dominant medical paradigm by underscoring the importance of
      helping clients contextualize and normalize dissociative behavior, and (c)
      highlighting specific characteristics of the therapeutic relationship that create
      the necessary trust and safety to facilitate reparation. A detailed description
      of the 3 major themes and 16 subthemes is provided. Implications for both
      clinical theory and practice are identified.

PMID- 19585340
TI  - The relationship between fatalism, dissociation, and trauma symptoms in Latinos.
AB  - Numerous studies have documented an overrepresentation of posttraumatic stress
      disorder in the Latino population. However, the contributing factors to trauma
      symptomatology among Latinos are not fully understood. The present study examined
      112 low-income, Latino outpatients in a mental health clinic to identify
      culturally relevant variables that predict trauma symptomatology. Fatalism,
      peritraumatic dissociation, acculturation, and demographic variables were
      analyzed. Peritraumatic dissociation was found to account for a significant
      percentage of the variance in trauma symptoms (21%) as measured by the
      Peritraumatic Dissociative Experiences Questionnaire-Modified and the Trauma
      Symptom Inventory. Fatalism measured by the Multiphasic Assessment of Cultural
      Constructs was not found to be significantly associated with symptom severity.
      Also, acculturation variables did not predict peritraumatic dissociation.
      Implications of the findings for trauma research and practice are discussed.

PMID- 19585339
TI  - Inpatient treatment for adult survivors of childhood sexual abuse: a preliminary
      outcome study.
AB  - The objective of this study was to examine the changes in psychiatric symptoms
      and interpersonal problems in 34 adults with a history of childhood sexual abuse
      and posttraumatic stress disorder who attended a 3-month inpatient treatment
      program. Levels of posttraumatic, depressive, and general psychiatric symptoms
      and interpersonal problems were assessed at pre-care evaluation, admission,
      discharge, and 1-year follow-up using the Impact of Event Scale, the Beck
      Depression Inventory, the Symptom Check List 90 Revised, and the Inventory of
      Interpersonal Problems. Work status was assessed at admission and at follow-up.
      Significant improvements were seen during treatment on the global scores of all
      instruments except the Beck Depression Inventory. At follow-up, patients had kept
      their gains on symptom measures and experienced further progress regarding
      interpersonal problems. At discharge, 3 of the previously 32 unemployed patients
      were able to return to work. Patients with comorbid somatization disorder tended
      to have higher levels of distress and less favorable treatment response. Future
      studies should include pre- and posttreatment assessment of dissociation to
      evaluate its association with outcome.

PMID- 19585341
TI  - Dissociation in borderline personality disorder: a detailed look.
AB  - The objective of the present study was to assess in detail the whole spectrum of
      normal and pathological dissociative experiences and dissociative disorder (DD)
      diagnoses in borderline personality disorder (BPD) as diagnosed with the Revised
      Diagnostic Interview for Borderlines. Dissociation was measured comprehensively
      in 21 BPD outpatients using the Structured Clinical Interview for DSM-IV
      Dissociative Disorders-Revised, the Multidimensional Inventory of Dissociation
      (MID), the Dissociative Experiences Scale pathological taxon analysis, and the
      Somatoform Dissociation Questionnaire. The frequencies of DDs in this BPD sample
      were as follows: 24% no DD, 29% mild DD (dissociative amnesia and
      depersonalization disorder), 24% DD Not Otherwise Specified (DDNOS), and 24%
      dissociative identity disorder. With regard to the dissociative experiences
      endorsed, almost all patients reported identity confusion, unexplained mood
      changes, and depersonalization. Even those BPD patients with mild DD reported
      derealization, depersonalization, and dissociative amnesia. BPD patients with
      DDNOS reported frequent depersonalization, frequent amnesia, and notable
      experiences of identity alteration. BPD patients with dissociative identity
      disorder endorsed severe dissociative symptoms in all categories. Analysis of the
      MID pathological dissociation items revealed that 32% of the items were endorsed
      at a clinically significant level of frequency by more than 50% of our BPD
      patients. In conclusion, the frequencies of Diagnostic and Statistical Manual of
      Mental Disorders (4th ed.) DDs in these patients with BPD were surprisingly high.
      Likewise, the "average" BPD patient endorsed a wide variety of recurrent
      pathological dissociative symptoms.

PMID- 19585345
TI  - An item response theory/confirmatory factor analysis of the Autobiographical
      Memory Test.
AB  - The Autobiographical Memory Test (AMT) is used to assess the degree of
      specificity of autobiographical memory. The AMT usually contains cue words of
      both positive and negative valence, but it is unclear whether these valences form
      separate factors or not. Accordingly, confirmatory factor analysis assessed
      whether the AMT measures one overall factor, or whether different cue types are
      related to different factors. Results were consistent across three datasets (N =
      333, N = 405, and N = 336). A one-factor model fitted each dataset well, which
      suggests that responses to positive and negative cues are related to the one
      construct. In addition, item response theory analyses showed that the AMT is most
      precise for people who score low on memory specificity. Implications for using
      the AMT with high-functioning samples are discussed.

PMID- 19585347
TI  - Lingering effects of inattention on the recognition of novel forms.
AB  - Two experiments are reported in which participants were instructed to attend to
      one of two overlapping figures and report how distinctive it was (Experiment 1),
      or how angular it was or what it resembled (Experiment 2). Tests of recognition
      memory indicated that recognition of the unattended figures was below chance,
      consistent with the conclusion that an implicit memory of the unattended figures
      and an "action tag" to not respond to the figures combine at recognition to
      suppress positive identification. Furthermore, participants that scored high on
      an index of working memory ability showed worse memory for the unattended shapes,
      suggesting that the ability to control attention not only enhances memory for
      attended items, but also leads to greater suppression of unattended distractors.

PMID- 19585346
TI  - Threat-related processing supports prospective memory retrieval for people with
      obsessive tendencies.
AB  - Obsessive-compulsive disorder can result in a variety of deficits to cognitive
      performance, including negative consequences for attention and memory
      performance. The question addressed in the current study concerned whether this
      disorder influenced performance in an event-based prospective memory task. The
      results from a subclinical population indicated that, relative to non-anxious
      controls and mildly depressed controls, people with obsessive-compulsive
      tendencies (washing compulsions) incur decrements in remembering to respond to
      cues related to a neutral intention (respond to animals). This deficit was
      ameliorated by giving the subclinical group an intention about a threat-related
      category (respond to bodily fluids) and cueing them with concepts that they had
      previously rated as particularly disturbing to them. Thus, their normal
      attentional bias for extended processing of threat-related information overcame
      their natural deficit in event-based prospective memory.

PMID- 19585348
TI  - Metal bar prevents phantom limb motion: case study of an amputation patient who
      showed a profound change in the awareness of his phantom limb.
AB  - This case report describes an amputee (patient A.S., a 60-year-old male forelimb
      amputee) who had an extraordinary experience with a phantom limb. He complained
      that he could not move the wrist of his phantom limb because a metal bar was
      perceived to be grasped by the hand. As a solution for removing the metal bar, we
      invited the patient to undergo mirror reflection-induced visual feedback therapy.
      The patient reported that the metal bar previously grasped by his hand was
      successfully removed from the phantom during the course of therapy.
      Interestingly, this experience was accompanied by profound changes in the EMG
      modulation in the residual wrist muscles. In this article, the possible
      mechanisms underlying this interesting phenomenon will be discussed.

PMID- 19585349
TI  - Opportunities to say 'yes': rare speech automatisms in a case of progressive
      nonfluent aphasia and apraxia.
AB  - We describe the investigation of speech automatisms in a man with progressive
      nonfluent aphasia and apraxias. Occurrence of the automatisms yes and right, were
      analysed across a range of speech tasks varying in length, propositionality,
      lexical and articulatory complexity, whether tasks engaged internal generation or
      external triggering and articulatory distortions, and while completing
      pantomimes/gestures. No differences were found in occurrence across most tasks
      but there was a significant interaction between automatism production and apraxic
      speech errors and during limb praxic tasks, suggesting that production of the
      automatism was unrelated to linguistic or lexical variables, but was related to
      the presence of speech apraxia coupled with disinhibition.

PMID- 19585351
TI  - A case of developmental deep dyslexia: what's left is right.
AB  - Cases of acquired deep dyslexia have not clearly and consistently supported any
      of the theoretical models. We report on a case of a 51-year-old right-handed
      female, L.S., with a developmental history of deep dyslexia in order to test the
      neuropsychological models using a visual half-field semantic priming paradigm.
      Word targets were primed either by a highly associated word (e.g., CLEAN-DIRTY),
      a weakly associated word (e.g., CLEAN-TIDY), or an unrelated word (e.g., CLEAN
      FAMILY) projected to either the same or opposite visual field (VF) as the target.
      In normals, RVF-left hemisphere primes result in high associate priming
      regardless of target location (ipsilateral or contralateral to the prime),
      whereas LVF-right hemisphere primes produce both high and low associate priming
      across both target location conditions (Hutchinson, Whitman, Abeare & Raiter,
      2003). In contrast, L.S. showed hyperpriming to both high and low associates only
      in the left hemisphere with inhibition of high associates in the right
      hemisphere. This case represents a variation of developmental deep dyslexia in
      which the patient's left hemisphere functions like a normal right hemisphere.
      However, the lack of exclusively high associate priming in the opposite (right)
      hemisphere may not provide the necessary narrowing of semantic activation
      necessary for normal reading and thus, may lead to semantic reading errors.
      Theoretical implications are discussed.

PMID- 19585352
TI  - Hyperlexia and ambient echolalia in a case of cerebral infarction of the left
      anterior cingulate cortex and corpus callosum.
AB  - We report the case of a 69-year-old woman with cerebral infarction in the left
      anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a
      distinctive reading phenomenon, as well as ambient echolalia. Clinical features
      also included complex disorders such as visual groping, compulsive manipulation
      of tools, and callosal disconnection syndrome. She read words written on the
      cover of a book and repeated words emanating from unrelated conversations around
      her or from hospital announcements. The combination of these two features due to
      a focal lesion has never been reported previously. The supplementary motor area
      may control the execution of established subroutines according to external and
      internal inputs. Hyperlexia as well as the compulsive manipulation of tools could
      be interpreted as faulty inhibition of preexisting essentially intact motor
      subroutines by damage to the anterior cingulate cortex reciprocally
      interconnected with the supplementary motor area.

PMID- 19585350
TI  - A slice of pi : an exploratory neuroimaging study of digit encoding and retrieval
      in a superior memorist.
AB  - Subject PI demonstrated superior memory using a variant of a Method of Loci (MOL)
      technique to recite the first digits of the mathematical constant pi to more than
      2(16) decimal places. We report preliminary behavioral, functional magnetic
      resonance imaging (fMRI), and brain volumetric data from PI. fMRI data collected
      while PI recited the first 540 digits of pi (i.e., during retrieval) revealed
      increased activity in medial frontal gyrus and dorsolateral prefrontal cortex.
      Encoding of a novel string of 100 random digits activated motor association
      areas, midline frontal regions, and visual association areas. Volumetric analyses
      indicated an increased volume of the right subgenual cingulate, a brain region
      implicated in emotion, mentalizing, and autonomic arousal. Wechsler Abbreviated
      Scale of Intelligence (WASI) testing indicated that PI is of average
      intelligence, and performance on mirror tracing, rotor pursuit, and the Silverman
      and Eals Location Memory Task revealed normal procedural and implicit memory.
      PI's performance on the Wechsler Memory Scale (WMS-III) revealed average general
      memory abilities (50th percentile), but superior working memory abilities (99th
      percentile). Surprisingly, PI's visual memory (WMS-III) for neutral faces and
      common events was remarkably poor (3rd percentile). PI's self-report indicates
      that imagining affective situations and high emotional content is critical for
      successful recall. We speculate that PI's reduced memory for neutral/non
      emotional faces and common events, and the observed increase in volume of the
      right subgenual cingulate, may be related to extensive practice with memorizing
      highly emotional material.

PMID- 19585353
TI  - The effects of cerebellar ataxia on sign language production: a case study.
AB  - Speech and sign production both require precise coordination of multiple
      articulators. The characteristics of dysarthria following ataxia have been well
      documented, but less is known about the consequences of ataxia for sign language,
      which uses the hands and arms as articulators. This is the first study to examine
      ataxic dysarthria in a sign language user. What is novel in this research is that
      the limbs are employed for both linguistic and non-linguistic movements. Notably,
      sign production deficits broadly resembled ataxic dysarthria, while non
      linguistic movement deficits were similar to those previously reported for ataxic
      limb movement.

PMID- 19585355
TI  - Cytokine and molecular analyses of intraocular lymphoma.
AB  - PURPOSE: The authors investigate the efficacy of using the cytokine levels and
      clonal heavy-chain immunoglobulin (IgH) gene rearrangements in the vitreous as
      adjunctive tools to diagnose intraocular lymphoma (IOL). METHODS: The IL-10 and
      IL-6 levels and IgH gene rearrangements were analyzed in vitreous samples from 8
      cases of IOL and in 14 uveitis patients. RESULTS: The level of IL-10 with an IL
      10/IL-6 ratio > 1 was significantly higher in all eyes with IOL. B-cell
      monoclonality was detected in only 5 of 8 eyes with IOL. CONCLUSIONS: The
      measurements of the levels of cytokines are valuable as a reliable biomarker.

PMID- 19585354
TI  - Primary intraocular lymphoma: diagnosis and differential diagnosis.
AB  - Diagnosis of PIOL can be challenging. It requires a high degree of clinical
      suspicion and differential diagnosis includes infectious and non-infectious
      etiologies particularly the common masquaraders sarcoidosis, tuberculosis, viral
      retinitis and syphilis. The definitive diagnosis depends on demonstration of
      malignant lymphoma cells in ocular specimens or CSF. Ocular specimen could
      include vitreous, aqueous or chorioretinal biopsy. Ocular pathologist should be
      consulted prior to the diagnostic procedure to help handle and process the
      specimen appropriately. In addition to cytology, flow cytometry,
      immunohistochemistry, molecular analysis and cytokines may be used as adjuncts in
      facilitating the diagnosis.

PMID- 19585356
TI  - Vitrectomy for endogenous fungal endophthalmitis.
AB  - PURPOSE: The purpose of this study was to evaluate the predisposing risk factors
      and treatment outcomes of endogenous fungal endophthalmitis (EFE). METHODS:
      Records of 25 patients (29 eyes), diagnosed with EFE and treated at Shanghai Eye,
      Ear, Nose & Throat Hospital from January 2002 to December 2006, were
      retrospectively reviewed. Four patients had bilateral disease. Final visual
      acuity and recurrence of EFE were evaluated. RESULTS: Of these 25 patients
      diagnosed with EFE, 20 patients (22 eyes) were treated by pars plana vitrectomy.
      Of the remaining 5 patients (7 eyes), 3 cases (4 eyes) were cured by antifungal
      drugs through systemic treatment and intravitreal injection, but another 2 cases
      (3 eyes) were only given intravitreal injection because of severe general
      conditions. Of the 22 eyes that underwent pars plana vitrectomy, 16 (73%) eyes
      gained visual acuity of counting fingers or better. Recurrent EFE was happened in
      2 eyes. Vitrectomy was repeated in 1 eye, another was subsequently enucleated due
      to phthisis. Vitreous culture-proven or smear-proven EFE occurred in 27 or 2
      eyes, respectively. Candida albicans occurred in 17 of 29 eyes (59%), and other
      causative organisms were yeast fungus (3 eyes), Aspergillus niger (3 eyes),
      Actinomyces (2 eyes),Aspergillus flavus (1 eye), and Fusarium (1 eye).
      CONCLUSION: Candida albicans were the most common causative organisms in EFE. The
      most common predisposing risk factors include recent major operation and
      intravenous administration in rural settings. Most patients with EFE will gain
      useful vision (counting fingers) after pars plana vitrectomy.

PMID- 19585357
TI  - Endogenous Klebsiella endophthalmitis associated with Klebsiella pneumoniae
      pneumonia.
AB  - PURPOSE: To investigate the management, bacterial strains, antibiotic
      sensitivities, and visual outcomes in patients with Klebsiella pneumoniae
      pneumonia and endogenous Klebsiella endophthalmitis. METHODS: Data were collected
      for treatments, antibiotic sensitivity patterns, and final visual outcomes.
      RESULTS: The study included 10 eyes of 9 patients with a median age of 42 years
      (range, 0-86 years). Diabetes mellitus was the most common comorbid risk factor
      (n = 5, 56%). Nine eyes (90%) were treated with intravitreal antibiotics, and one
      with pars plana vitrectomy and intravitreal antibiotics. One eye achieved a
      favorable visual acuity of 20/20; however, 6 eyes developed vision of no light
      perception, including 2 of evisceration. Two nosocomial K. pneumoniae isolates
      were extended-spectrum-beta-lactamase-producing strains, which demonstrated the
      resistance to amikacin and ceftazidime. CONCLUSIONS: Ophthalmologists and
      physicians should be aware of Klebsiella pneumonia as a possible cause of
      endogenous endophthalmitis, and endogenous Klebsiella endophthalmitis usually
      causes poor visual outcomes.

PMID- 19585359
TI  - Ocular features in neurosarcoidosis.
AB  - BACKGROUND/AIMS: To determine the type of ocular involvement in patients with
      neurosarcoidosis, and evaluate whether the type of eye involvement may help in
      the diagnosis of neurosarcoidosis. METHODS: Retrospective, case history study. We
      reviewed the medical records of 46 patients who attended the sarcoidosis clinics
      at the Royal Brompton and Moorfields Eye Hospital over a 4-year period with a
      diagnosis of definite and probable neurosarcoidosis supported by laboratory
      investigations and exclusion of other causes for the neurological symptoms.
      RESULTS: Cranial nerve involvement was the most common neurological manifestation
      in this series. Among the 27 patients with cranial neuropathy, lower motor
      neurone facial palsy was the most frequently seen in 19 patients (70.4%).
      Diplopia was seen in four patients (14.9%). In three patients, this was because
      of common oculomotor nerve paresis. Uveitis was the most common intraocular
      manifestation in patients with neurosarcoidosis. The majority of these patients
      (9, 64.3%) suffered from anterior uveitis, but in 35.7% of them the inflammatory
      process involved the posterior segment. CONCLUSIONS: We found a higher incidence
      of ocular manifestations, including intraocular inflammation in neurosarcoidosis
      compared to that in systemic sarcoidosis elsewhere. The most common ocular
      complication seen in our series was anterior uveitis; however there were no
      associated clinical features of the uveitis in these series that could contribute
      to the differential diagnosis between neurosarcoidosis and other autoimmune
      disorders with neuro-ophthalmic features such as multiple sclerosis. Patients
      with neurological symptoms and associated intraocular inflammation should have a
      routine work-up for sarcoidosis. Investigations should include MRI scan of the
      brain and orbits and lumbar puncture in selected cases. Tissue biopsy should be
      attempted when clinically accessible lesions are available i.e., conjunctiva or
      lacrimal gland.

PMID- 19585358
TI  - International criteria for the diagnosis of ocular sarcoidosis: results of the
      first International Workshop On Ocular Sarcoidosis (IWOS).
AB  - AIM: To report criteria for the diagnosis of intraocular sarcoidosis, taking into
      account suggestive clinical signs and appropriate laboratory investigations and
      biopsy results. DESIGN: Concensus workshop of an international committee on
      nomenclature. METHODS: An international group of uveitis specialists from Asia,
      Africa, Europe, and America met in a concensus conference in Shinagawa, Tokyo on
      October 28-29, 2006. Based on questionnaires that had been sent out prior to the
      conference, the participants discussed potential intraocular clinical signs
      eligible for a diagnosis of ocular sarcoidosis. A refined definition of clinical
      signs, which received two-thirds majority of votes, was included in the list of
      signs consistent with ocular sarcoidosis. Laboratory investigations were
      similarly discussed and those tests reaching a two-thirds majority were retained
      for the diagnosis of ocular sarcoidosis. Finally diagnostic criteria were
      proposed based on ocular signs, laboratory investigations, and biopsy results.
      RESULTS: The concensus conference identified seven signs in the diagnosis of
      intraocular sarcoidosis: (1) mutton-fat keratic precipitates (KPs)/small
      granulomatous KPs and/or iris nodules (Koeppe/Busacca), (2) trabecular meshwork
      (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS), (3) vitreous
      opacities displaying snowballs/strings of pearls, (4) multiple chorioretinal
      peripheral lesions (active and/or atrophic), (5) nodular and/or segmental peri
      phlebitis (+/- candlewax drippings) and/or retinal macroaneurism in an inflamed
      eye, 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and
      (7) bilaterality. The laboratory investigations or investigational procedures
      that were judged to provide value in the diagnosis of ocular sarcoidosis in
      patients having the above intraocular signs included (1) negative tuberculin skin
      test in a BCG-vaccinated patient or in a patient having had a positive tuberculin
      skin test previously, (2) elevated serum angiotensin converting enzyme (ACE)
      levels and/or elevated serum lysozyme, (3) chest x-ray revealing bilateral hilar
      lymphadenopathy (BHL), (4) abnormal liver enzyme tests, and (5) chest CT scan in
      patients with a negative chest x-ray result. Four levels of certainty for the
      diagnosis of ocular sarcoidosis (diagnostic criteria) were recommended in
      patients in whom other possible causes of uveitis had been excluded: (1) biopsy
      supported diagnosis with a compatible uveitis was labeled as definite ocular
      sarcoidosis; (2) if biopsy was not done but chest x-ray was positive showing BHL
      associated with a compatible uveitis, the condition was labeled as presumed
      ocular sarcoidosis; (3) if biopsy was not done and the chest x-ray did not show
      BHL but there were 3 of the above intraocular signs and 2 positive laboratory
      tests, the condition was labeled as probable ocular sarcoidosis; and (4) if lung
      biopsy was done and the result was negative but at least 4 of the above signs and
      2 positive laboratory investigations were present, the condition was labeled as
      possible ocular sarcoidosis. CONCLUSION: Various clinical signs, laboratory
      investigations, and biopsy results provided four diagnostic categories of sarcoid
      uveitis. The categorization allows prospective multinational clinical trials to
      be conducted using a standardized nomenclature, which serves as a platform for
      comparison of visual outcomes with various therapeutic modalities.

PMID- 19585360
TI  - Fluorodeoxyglucose positron emission tomography for the diagnosis of sarcoidosis
      in patients with unexplained chronic uveitis.
AB  - PURPOSE: To assess the value of fluorine-18 fluorodeoxyglucose positron emission
      tomography ((18)F-FDG PET) in patients with unexplained chronic uveitis. METHODS:
      Retrospective review of 19 (18)F-FDG PET scans. All patients had normal chest CT.
      In the final analysis, the authors used criteria similar to the criteria of Abad
      et al. (Abad S, Meyssonier V, Allali J, et al. Association of peripheral
      multifocal choroiditis with sarcoidosis: a study of thirty-seven patients.
      Arthritis Rheum. 2004;51:974-982) for the diagnosis of sarcoidosis-associated
      uveitis. RESULTS: Ten (53%) whole-body scans were consistent with sarcoidosis. At
      the end, subsequent mediastinal biopsies proved sarcoidosis in 3 patients; 2
      patients were considered as presumed sarcoidosis, and 6 indeterminate
      sarcoidosis. CONCLUSION: (18)F-FDG PET may show focal uptake suggestive of
      sarcoidosis in patients with unexplained uveitis.

PMID- 19585361
TI  - Mycophenolate mofetil therapy for sarcoidosis-associated uveitis.
AB  - PURPOSE: To evaluate the control of ocular inflammation and the steroid sparing
      effect in patients with sarcoidosis-associated uveitis treated with mycophenolate
      mofetil (MMF). METHODS: Retrospective case series. All patients with a diagnosis
      of sarcoidosis-associated uveitis that were treated with MMF between 2005 and
      2007 were identified. The dose and duration of MMF therapy and side effects were
      recorded. RESULTS: Seven patients (14 eyes) with sarcoidosis-associated uveitis
      were treated with MMF. The mean duration of treatment was 10 +/- 4.7 months and
      the average time to control uveitis was 6.7 weeks. The flare-up rate was 51.5 per
      100 person-years follow-up. The best-corrected mean logMAR VA revealed
      improvement in all 14 eyes. The efficacy of MMF in keeping disease activity under
      control was maintained in 6 patients. CONCLUSION: These data suggest that MMF is
      effective in controlling sarcoidosis-related ocular inflammation, has a
      corticosteroid sparing effect and a manageable side-effect profile.

PMID- 19585362
TI  - Anterior ischemic optic neuropathy associated with pegylated interferon therapy
      for chronic hepatitis C.
AB  - PURPOSE: To report a case of anterior ischemic optic neuropathy (AION) associated
      with the combined therapy of pegylated interferon alpha (PEG-IFNalpha) and
      ribavirin. METHODS: Case report. RESULTS: A 57-year-old male with chronic
      hepatitis C, treated with PEG-IFNalpha -2b and ribavirin for 6 months, noted
      sudden onset of painless blurred vision in his right eye. The initial visual
      acuity decreased to 20/60 in the right eye. Fundoscopy of right eye revealed
      optic disc edema with disc hemorrhage. Visual field examination disclosed
      inferior altitudinal defect. Relative afferent pupillary defect with poor color
      vision function was also noted in the right eye. Visual evoked potential
      demonstrated decreased amplitude in the right eye. A marked resolution of disc
      edema and improvement of visual acuity to 20/20 were noted at 6 weeks follow-up.
      CONCLUSIONS: AION may occur in combined treatment of PEG-IFNalpha -2b and
      ribavirin for chronic hepatitis C. Patients who are candidates for this treatment
      should be informed about its possible occurrence.

PMID- 19585363
TI  - Intravitreal anakinra inhibits choroidal neovascular membrane growth in a rat
      model.
AB  - PURPOSE: To determine the effect of intravitreal anakinra on choroidal
      neovascularization (CNV) in an animal model. METHODS: Laser photocoagulation used
      to rupture Bruch's membrane; animals then assigned to groups based on varying
      frequency of intravitreal anakinra injections. At day 30, digital angiography was
      used to measure the CNV area. RESULT: Intravitreal anakinra dose-dependently
      inhibited CNV growth. Injections given one time resulted in a 26% reduction in
      CNV; in the once weekly group, a 41% reduction was seen; in the twice-weekly
      group, a 62% reduction was seen (all p < .001). CONCLUSION: Suppressing IL-1
      function may provide another therapeutic avenue in exudative AMD.

PMID- 19585364
TI  - Interleukin-1 and tumor necrosis factor-alpha: novel targets for immunotherapy in
      Eales disease.
AB  - BACKGROUND: Eales disease is an idiopathic obliterative vasculopathy that
      primarily affects the peripheral retina of young adults. The authors evaluated
      interleukin 1 beta (IL-1beta), interleukin-6 (IL-6), Interleukin-10 (IL-10), and
      tumor necrosis factor-alpha (TNF-alpha) in the serum of patients with Eales
      disease stages for the first time. METHODS: The study group consisted of 45
      consecutive patients of Eales disease [inflammatory stage (n = 15) and
      proliferative stage (n = 30)] and 28 healthy controls. Immunoassays for the
      quantification of the levels of four cytokines including IL-1beta, IL-6, IL-10,
      and TNF-alpha in the serum samples were performed using ELISA kits. RESULTS: IL
      1beta, IL-6, IL-10, and TNF-alpha levels were found to be increased significantly
      in the inflammatory stage of Eales disease as compared to controls (p < .001). IL
      1beta levels decreased significantly during the proliferative stage of the
      disease as compared to the inflammatory stage (p = .03). TNF-alpha levels
      increased significantly during the proliferative stage as compared to the
      inflammatory stage (p = .02). CONCLUSIONS: Raised levels of IL-1beta and TNF
      alpha were observed in the inflammatory stage and persisted in the proliferative
      stage of the disease. The IL-1 system and TNF-alpha represent novel target for
      immunotherapy for controlling inflammatory activity and/or the associated long
      term sequelae related to angiogenesis in Eales disease.

PMID- 19585365
TI  - Ocular syphilis--back again: understanding recent increases in the incidence of
      ocular syphilitic disease.
AB  - PURPOSE: The clinical findings and outcomes of 12 cases of luetic uveitis are
      reported. METHODS: Review of clinical records. RESULTS: Patients included 10 men
      and 2 women; 7 were homosexual, 9 HIV-positive. Six patients presented a medical
      history suggestive of syphilis. All patients presented with iritis and vitritis.
      Visual acuity improved in 11 patients after treatment. CONCLUSIONS: Syphilis has
      reemerged in developed countries. This may be related to the post-AID S/HAART
      era, with a growing pool of HIV-positive men who oftenly practice unsafe sex. We
      underscore the importance of a high index of suspicion of ocular syphilis in
      patients with these characteristics.

PMID- 19585366
TI  - Ocular syphilis unmasked following intravitreal triamcinolone injection.
AB  - PURPOSE: To report intravitreal triamcinolone (IVTA)-induced unmasking of ocular
      syphilis. DESIGN: Two case reports. METHODS: A homosexual, diabetic male with
      macular edema treated with bilateral IVTA and a male with bilateral panuveitis
      and macular edema who underwent vitrectomy and IVTA. Both developed occlusive
      retinal vasculitis and panuveitis postinjection. Syphilis serology was positive
      although both denied previous symptoms. RESULTS: Intramuscular penicillin lead to
      resolution of inflammation but both sustained severe loss of vision. Cause-and
      effect relationship demonstrated between IVTA and reactivation of syphilis.
      CONCLUSIONS: Intravitreal corticosteroid can modulate the immune response to
      intraocular syphilis; vigilance is required, particularly in high-risk patients.

PMID- 19585367
TI  - Vitreous concentration of triamcinolone acetonide after a single transseptal
      depot injection.
AB  - PURPOSE: To determine vitreous concentrations of triamcinolone acetonide(TA)
      following transseptal injection. METHODS: TA (40 mg/l ml) was administered at
      varying intervals prior to vitrectomy. Vitreous samples from 18 patients were
      obtained. TA concentrations were quantified using HPLC-MS. RESULTS: Vitreous
      levels of TA were detected in all samples (range 0.64-168.0 ng/ml). The interval
      from injection to sampling ranged from 0.5-20 days. Tmax was attained at 0.5
      days. TA concentrations were negatively correlated with scleral thickness (P =
      0.0184) and depot location (P = 0.0230) but not with PVD status (P = 0.9633).
      CONCLUSION: Significant vitreous concentrations of TA are achieved after a single
      transseptal injection. Scleral thickness, depot location and time influence
      vitreous TA levels.

PMID- 19585368
TI  - Combined intravitreal bevacizumab and triamcinolone acetonide injection for
      idiopathic neuroretinitis.
AB  - PURPOSE: To present a case with idiopathic neuroretinitis that was treated with
      combined intravitreal bevacizumab and triamcinolone. DESIGN: Case report.
      METHODS: Interventional case report. RESULTS: A 31-year-old man presented with a
      visual acuity of 3/10 and afferent pupillary defect in the right eye.
      Ophthalmologic examination disclosed papillitis and macular edema. Neurology
      consultation with cranial computerized tomography scan revealed no abnormality.
      The patient was injected with bevacizumab and triamcinolone intravitreally. One
      week later, the vision increased to 10/10, macular edema disappeared. One month
      later, optic disc edema disappeared. CONCLUSIONS: Intravitreal injection of
      bevacizumab and triamcinolone effectively treated idiopathic neuroretinitis.

PMID- 19585370
TI  - Methodological background of decision rules and feedback tools for outcomes
      management in psychotherapy.
AB  - Systems to provide feedback regarding treatment progress have been recognized as
      a promising method for the early identification of patients at risk for treatment
      failure in outpatient psychotherapy. The feedback systems presented in this
      article rely on decision rules to contrast the actual treatment progress of an
      individual patient and his or her expected treatment response (ETR). Approaches
      to predict the ETR on the basis of patient intake characteristics and previous
      treatment progress can be classified into two broad classes: Rationally derived
      decision rules rely on the judgments of experts, who determine the amount of
      progress that a patient has to achieve for a given treatment session to be
      considered "on track." Empirically derived decision rules are based on expected
      recovery curves derived from statistical models applied to aggregated
      psychotherapy outcomes data. Examples of each type of decision rule and of
      feedback systems based on such rules are presented and reviewed.

PMID- 19585371
TI  - Modeling psychotherapy process by time-series panel analysis (TSPA).
AB  - The authors introduce the methodology of aggregated time-series analysis (time
      series panel analysis [TSPA]), by which prototypical process patterns are
      estimated using longitudinal psychotherapy process data. Empirical trajectories
      of 202 outpatients (15-107 sessions) were available. Presession questionnaires
      provided measures of patient's well-being and patient's therapy motivation. TSPA
      was contrasted with growth curve modeling. Fixed effects were estimated in both
      methods. Unbalanced longitudinal data considering multiple levels can be
      analyzed. Using Granger causality derived from time-lagged associations, the TSPA
      pattern revealed feedback relationships between well-being and therapy
      motivation. Growth curve analysis highlighted logarithmic increases of well-being
      trajectories. In particular, TSPA can illuminate change mechanisms in
      psychotherapy field data by its nonexperimental approximation to an analysis of
      causal dynamic structures.

PMID- 19585373
TI  - Desirable pharmacokinetic properties of (13)C-uracil as a breath test probe of
      gastric emptying in comparison with (13)C-acetate and (13)C-octanoate in rats.
AB  - OBJECTIVE: To investigate the possible use of a (13)C-uracil breath test for
      gastric emptying by evaluating the pharmacokinetic properties of (13)C-uracil in
      a breath test in rats, in comparison with (13)C-acetate and (13)C-octanoate,
      traditional (13)C-probes for gastric emptying. MATERIAL AND METHODS: Absorption
      of the (13)C-probes from different parts of the gastrointestinal tract was
      evaluated in fasted rats. (13)C-Uracil breath tests for gastric emptying were
      carried out in conditions where delayed gastric emptying was induced by
      clonidine, quinpirole, and propantheline, and in a postoperative ileus model.
      Following oral administration, we measured residual (13)C-uracil in the stomach
      and correlated the amount with the breath response. RESULTS: All the (13)C-probes
      employed were well absorbed from the intestine after intraduodenal
      administration. After intragastric administration, (13)C-uracil was not absorbed
      from the stomach, but (13)C-acetate and (13)C-octanoate were partly absorbed from
      the stomach. The cumulative (14)C-uracil recovery (%) at 168 h was 92.3, 6.3, or
      0.5%, from expired gases, urine, and feces, respectively. Delta(13)C values in
      (13)C-uracil breath tests were decreased in conditions characterized by delayed
      gastric emptying. A highly negative correlation was observed between the breath
      response and the residual ratio of (13)C-uracil in the stomach after oral
      administration of (13)C-uracil, indicating that (13)C-uracil can be used as an in
      vivo probe for evaluating gastric emptying in a quantitative manner. CONCLUSIONS:
      This study showed that (13)C-uracil has desirable pharmacokinetic properties as
      an in vivo probe of gastric emptying. It is thus suggested that the (13)C-uracil
      breath test may be useful for the measurement of gastric emptying in humans.

PMID- 19585374
TI  - Is asymptomatic pancreatic hyperenzymemia the same condition in adults and in
      children?

PMID- 19585375
TI  - Atypical retroperitoneal fibrosis associated with biliary stricture: IgG4-related
      sclerosing disease?

PMID- 19585376
TI  - Prospective observational study of the incidental findings on endoscopic
      ultrasonography: should a complete exploration always be performed?
AB  - OBJECTIVES: To quantify the additional non-suspected new diagnoses made on upper
      endosonography (EUS) which were unknown before the procedure, and to analyse
      their influence on the management of patients. A further objective was to
      evaluate the influence that previous radiological or endoscopic explorations have
      on the capacity of EUS to diagnose these unsuspected lesions. MATERIAL AND
      METHODS: During a 2-year period every patient sent to our unit for upper EUS
      underwent a complete investigation, after signing an informed consent document.
      An upper EUS was considered as complete whenever the gut wall, pancreas, biliary
      tract, ampulla, large abdominal vessels, liver, spleen, left adrenal gland,
      posterior mediastinum and thyroid lobes had been explored. An additional
      diagnosis (AD) was defined as a diagnosis made on EUS that was previously unknown
      and not suspected. A significant additional diagnosis (SAD) was defined as an AD
      that required further study. The results of complementary explorations carried
      out before EUS were registered. RESULTS: A total of 239 patients were included in
      the study. ADs were found in 92 patients (38.5%), which were considered to be
      SADs in 27 patients (11.3%). Those patients had previously undergone computed
      tomography (CT) and those who underwent more than one exploration had fewer
      incidences of ADs on EUS (p=0.03 and p=0.02, respectively). No exploration alone
      or in combination with others showed any influence on the capacity of EUS to find
      a SAD (p >0.05). CONCLUSIONS: In our series, an AD was found on upper
      endosonography in 38.5% of the patients studied, and a SAD in 11.3%. The
      probability of finding a SAD on EUS is not influenced by previous endoscopic or
      radiologic explorations.

PMID- 19585377
TI  - Vocational intervention based on the Model of Human Occupation: a review of
      evidence.
AB  - Work is a growing concern in disability and rehabilitation fields. Specific
      evidence related to occupational therapy in the area of vocational rehabilitation
      is somewhat limited. With increased demands for occupation-focused, evidence
      based, and theory-informed practice, this review aims to use clinically relevant
      questions to organize and synthesize evidence regarding work-related
      interventions specifically related to an occupation-focused theory, the Model of
      Human Occupation. A total of 45 published works related to both the MOHO and
      vocational issues were identified and included in the review. The review
      demonstrates that there is a range of evidence that supports the use of the MOHO
      and its tools as a basis for work-based clinical interventions. Evidence supports
      the conclusion that MOHO-based work assessments have good psychometric properties
      and are useful in evaluating vocational potential and needs. MOHO-based work
      programs have been shown to have a positive impact in improving vocational
      outcomes to a range of clients.

PMID- 19585378
TI  - Coronary atherosclerosis using computed tomography coronary angiography in
      patients with systemic sclerosis.
AB  - BACKGROUND: Impaired coronary artery reserve has previously been demonstrated in
      patients with systemic sclerosis (SSc). Both micro- and macrovascular factors are
      probably contributory to the underlying pathogenesis. OBJECTIVES: To examine the
      frequency of coronary atherosclerosis in a series of SSc patients by computed
      tomography coronary angiography (CTCA), a less invasive method than conventional
      coronary angiography, the current gold standard in the detection of coronary
      atherosclerosis, and to explore its clinical associations. METHODS: Nineteen
      consecutive SSc patients [six with diffuse (dSSc) and 13 with limited disease
      (lSSc)] with disease duration of >or= 3 years were recruited. Coronary calcium
      score and contrast angiography were examined by CT scan. Conventional
      cardiovascular factors and inflammatory markers were measured and correlated with
      CT findings. RESULTS: The mean+/-SD age of these patients was 52.5+/-12.5 years
      with median disease duration of 12.5 years. Six (31.6%) patients were found to
      have coronary artery calcification (calcium score 13-2008). Coronary calcium was
      detected in one dSSc patient but contrast angiography was not performed because
      of interference from an in situ implantable cardiac device. Some parts of the
      coronary arteries were not assessable in two patients who had ectopic cardiac
      rhythm. Five lSSc patients had calcified plaques causing variable coronary
      luminal stenosis. All patients were asymptomatic. Patients with abnormal CTCA
      findings were more likely to be older (p < 0.001) and were less likely to have
      serum anti-Scl70 antibodies (p = 0.003) than those without, after Bonferroni
      correction. CONCLUSIONS: Coronary atherosclerosis is not uncommon in asymptomatic
      SSc patients. CTCA is a convenient and non-invasive method for studying coronary
      atherosclerosis.

PMID- 19585379
TI  - Comparison of three rheumatoid arthritis disease activity scores in clinical
      routine.
AB  - OBJECTIVE: To evaluate whether the revised disease activity cut-off values for
      the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity
      Index (CDAI) are in congruence with the Disease Activity Score including a 28
      joint count (DAS28) disease activity criteria in daily clinical routine. PATIENTS
      AND METHODS: A total of 570 rheumatoid arthritis (RA) outpatients were assessed
      and categorized according to the DAS28, the SDAI, and the CDAI. These results
      were compared to the respective DAS28 disease activity categories. Statistical
      evaluation was carried out by calculating alpha, the Spearman rank correlation,
      and kappa-statistics. RESULTS: DAS28, SDAI, and CDAI levels were significantly
      correlated to one another on a group level (p < 0.001). Internal consistency was
      the highest for the CDAI (alpha = 0.783) and the lowest for the DAS28 (alpha =
      0.664). Kappa-statistics revealed a substantial degree of agreement with respect
      to mild, moderate, and high disease activity according to the three scores, with
      exceptions concerning the definition of a remission-like state. Further
      categorization showed that an additional 44% of patients were found to be in
      remission according to the DAS28 disease activity criteria relative to those
      defined by the SDAI or the CDAI disease activity categories respectively.
      CONCLUSION: The revised SDAI limits for disease activity and the respective CDAI
      thresholds proved to be in congruence with the DAS28 disease activity categories
      in daily clinical routine. The SDAI and the CDAI were found to be more stringent
      in defining remission.

PMID- 19585381
TI  - Patient experiences of rehabilitation in rheumatology: association with process
      and outcome.
AB  - OBJECTIVE: To evaluate health-care experiences of patients following inpatient
      rheumatology rehabilitation and to assess the association between these
      experiences and aspects of health-care delivery and patient characteristics.
      METHODS: Data were collected from 435 patients with a rehabilitation stay of >or=
      1 week at 12 institutions in Norway in 2006. At discharge, patients completed the
      Rehabilitation Patient Experiences Questionnaire (Re-PEQ), which includes four
      important aspects of patient experiences. Multiple regression analysis was used
      to assess associations between Re-PEQ scores, health-care process, health and
      sociodemographic variables. RESULTS: A total of 412 (94.7%) patients completed
      the Re-PEQ; scores ranged from 69 (social environment) to 83 (care/organization)
      on the 0-100 scale, where 100 represents the best possible experience. The social
      environment scale had the largest component of variation explained by the
      independent variables, which included number of doctor visits, amount of group
      education, and individual exercise (p < 0.01). The type of institution, number of
      doctor visits, mental health, and gender also explained significant components of
      variation in the other Re-PEQ scale scores. CONCLUSION: Patients reported good
      experiences with rheumatology rehabilitation. Areas where poorer experiences
      emerged can help target areas for future initiatives aimed at improving the
      quality of care. Health and sociodemographic variables should be controlled for
      in studies of patient experiences.

PMID- 19585382
TI  - Health status and perception of pain: a comparative study between female patients
      with hand osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is the most frequent rheumatic joint disease and
      its occurrence is growing due to prolonged life expectancy and an increasing
      number of elderly individuals in the population. The main objective of this study
      was to compare the burden of disease, assessed by measures of pain and health
      related quality of life (HRQoL), between female patients with hand osteoarthritis
      (HOA) and rheumatoid arthritis (RA). METHODS: One hundred and ninety female HOA
      patients were compared with 194 female RA patients of the same age. HRQoL was
      measured with the Arthritis Impact Measurement 2 Scale (Aims2), the 36-item Short
      Form Health Survey (SF-36) and its preference-based single index measure SF-6D,
      the Health Assessment Questionnaire (HAQ), the modified HAQ (MHAQ), self-efficacy
      scales, and visual analogue scales (VAS) for pain and fatigue. We also compared
      levels of fibromyalgia (FM)-like symptoms (headache, muscle pain, numbness, and
      concentration problems). Scores were compared by a multivariate analysis of
      covariance (ANCOVA), adjusted for age, number of comorbidities, and years of
      education. Sime's procedure was used to adjust for multiple testing. RESULTS: RA
      patients had significantly lower levels of physical functioning compared to HOA
      patients, whereas pain measured on the Arthritis Impact Measurement Scale 2
      (AIMS2) was significantly worse in HOA as compared with RA. The HOA patients also
      had worse scores for FM-like symptoms. SF-6D utility scores in HOA and RA were
      similar (0.63 and 0.64, respectively). CONCLUSIONS: The overall impact of the
      disease on HRQoL was similar between RA and HOA patients, based on the SF-6D
      scores. Physical function was worse in RA patients, but HOA patients reported
      worse scores in pain measures and FM-like symptoms.

PMID- 19585384
TI  - Rituximab therapy in patients with rheumatoid arthritis refractory or with
      contraindication to anti-tumour necrosis factor drugs: real-life experience in
      Finnish patients.
AB  - OBJECTIVES: To describe the effects of rituximab therapy in patients with
      rheumatoid arthritis (RA) in routine clinical practice in Finland. METHODS: Data
      were collected retrospectively from patient records in five rheumatology clinics
      in Finland. All RA patients treated during 2005-2008 (n = 81) were included.
      Information on disease-modifying anti-rheumatic drugs (DMARDs), DMARD
      combinations, and biologics prior to rituximab use was collected as well as
      treatment responses after initiating rituximab therapy. The Disease Activity
      Score using 28 joint counts (DAS28) was used to determine disease activity and
      European League Against Rheumatism (EULAR) responses. RESULTS: Mean disease
      duration was 14 (range 0-47) years and the median number of prior DMARDs and
      biologics used were 7 (1-12) and 2 (0-4), respectively. Efficacy analysis was
      performed on 57 patients with available DAS28 data at treatment onset and follow
      up visits. Median DAS28 declined from 6.07 (3.19-7.70) to 3.99 (1.53-6.55) by the
      first rituximab treatment course. Altogether 77% of the patients achieved a EULAR
      response, 26% with a good response including 18% with remission. Furthermore, the
      patients treated concomitantly with DMARDs other than methotrexate (MTX) achieved
      a EULAR response slightly more often than the patients on MTX (85% vs. 70%) only.
      A second course of rituximab was given to 48% of the patients on an average of 9
      months after initial therapy, with the median DAS28 score declining further to
      3.49 (0.1-5.74). Safety and tolerability assessment of the 81 patients indicates
      rituximab to be well tolerated. CONCLUSIONS: Rituximab can effectively control
      disease activity in patients with active disease and poor response to previous
      therapies, in combination with MTX but also with other DMARDs.

PMID- 19585385
TI  - Intraurethral prostate injections with mepivacaine epinephrine: effects on
      patient comfort, treatment time and energy consumption during high-energy
      transurethral microwave thermotherapy.
AB  - OBJECTIVE: To investigate the effects of intraprostatic mepivacaine epinephrine
      injections administered by the Schelin catheter during high-energy transurethral
      microwave thermotherapy (TUMT) using the CoreTherm Prostalund Feedback Treatment
      (PLFT) system. MATERIAL AND METHODS: The study included 85 men with lower urinary
      tract symptoms due to benign prostatic enlargement. One group had intraprostatic
      injections with mepivacaine epinephrine by the new Schelin catheter, while
      patients in the other group were treated without intraprostatic injections. All
      men were treated by TUMT using the PLFT system. Before treatment, transrectal
      ultrasound (TRUS) volume was measured. During the procedure, treatment time,
      energy consumption, cell-kill parameter and maximal prostate temperature were
      recorded. Patients who needed perioperative intravenous analgesics and the rate
      of perioperative and postoperative complications were registered. RESULTS: The
      patients who had intraprostatic and periprostatic injections with mepivacaine
      epinephrine had shorter effective treatment time and reduced energy consumption.
      There was also a difference between the two groups in that 70% of patients
      without intraprostatic injections and only 11% of injected patients needed
      intravenous analgesics. No differences were found in TRUS volume, estimated cell
      kill, maximal prostate temperature or complication rates. CONCLUSIONS:
      Intraprostatic injections with mepivacaine epinephrine distributed by the Schelin
      catheter reduce the number of patients needing intravenous analgesics during
      PLFT, as well as the treatment time and energy consumption during treatment.
      Besides improved patient comfort, intraprostatic and periprostatic injections
      condense the treatment time without side-effects, making PLFT less cumbersome for
      most patients.

PMID- 19585386
TI  - Effect of motion smoothness on brain activity while observing a dance: An fMRI
      study using a humanoid robot.
AB  - Motion smoothness is critical in transmitting implicit information of body
      action, such as aesthetic qualities in dance performances. We expected that the
      perception of motion smoothness would be characterized by great intersubject
      variability deriving from differences in personal backgrounds and attitudes
      toward expressive body actions. We used functional magnetic resonance imaging and
      a humanoid robot to investigate the effects of the motion smoothness of
      expressive body actions and the intersubject variability due to personal
      attitudes on perceptions during dance observation. The effect of motion
      smoothness was analyzed by both conventional subtraction analysis and functional
      connectivity analyses that detect cortical networks reflecting intersubject
      variability. The results showed that the cortical networks of motion- and body
      sensitive visual areas showed increases in activity in areas corresponding with
      motion smoothness, but the intersubject variability of personal attitudes toward
      art did not influence these active areas. In contrast, activation of cortical
      networks, including the parieto-frontal network, has large intersubject
      variability, and this variability is associated with personal attitudes about the
      consciousness of art. Thus, our results suggest that activity in the cortical
      network involved in understanding action is influenced by personal attitudes
      about the consciousness of art during observations of expressive body actions.

PMID- 19585387
TI  - The increasing number of female general practitioners: why we need to change
      medical culture.

PMID- 19585389
TI  - Differential effects of constraints in the processing of Russian cataphora.
AB  - Anaphoric relations between pronouns and their antecedents are subject to a
      number of different linguistic constraints, which exclude the possibility of
      coreference in specific syntactic or discourse contexts. Constraints on anaphora
      may, in principle, impact online sentence processing in a couple of different
      ways. They may act as constraints on the generation of interpretations,
      preventing illicit anaphoric relations from ever being considered. Alternatively,
      they may act as later filters on interpretations, rejecting candidate
      interpretations after initial consideration. A number of previous studies have
      sought to determine which of these mechanisms accurately describes the online
      impact of constraints on anaphora. The current studies present evidence that
      there is no uniform answer to this question, and that the two mechanisms are both
      used, for different constraints. Evidence for this is drawn from studies on the
      processing of two constraints on backwards anaphora or cataphora in Russian that
      apply in superficially similar contexts but that differ in a number of respects.
      One self-paced reading study and two judgement studies are reported. The self
      paced reading study manipulates the gender congruency between a pronoun and a
      following name in three pairs of conditions. In conditions where the pronoun-name
      configuration violates no constraints on anaphora a gender mismatch effect was
      observed following the name, as in previous studies, suggesting that
      comprehenders actively search for an antecedent following a cataphoric pronoun.
      In conditions where the pronoun-name configuration violates Principle C of the
      classical binding theory no effect of the gender manipulation was observed,
      suggesting that comprehenders do not even consider the possibility of
      interpretations that violate this constraint. In conditions where the pronoun
      name configuration violates a Russian-specific constraint on cataphora a gender
      match effect was observed following the name, the reverse of the finding in the
      no-constraint conditions, suggesting that the constraint applies as a filter on
      candidate interpretations.

PMID- 19585388
TI  - Diagnosis and management of patients with hand and wrist problems in general
      practice.
AB  - OBJECTIVES: 1) To describe diagnoses made by general practitioners (GPs) in
      patients with hand or wrist problems, 2) to describe management, and 3) to
      determine the association between diagnostic information and two outcomes:
      persistent symptoms and specialist referral. METHODS: GPs recruited patients with
      hand or wrist problems and completed a standardized form recording information
      about patient history, observations, palpation, and physical tests. Patients were
      sent a questionnaire at baseline, 3, and 12 months, containing questions on
      characteristics and symptom severity. Logistic regression analyses were used to
      determine the association between diagnostic information and the odds of
      persistent symptoms or specialist referral. RESULTS: The three most frequently
      recorded diagnoses were osteoarthritis (17%), tenosynovitis (16%), and nerve
      entrapment (13%). "Wait and see" (30%) and painkillers (24%) were most often
      advised. Higher probability of persistent symptoms at both 3 and 12 months was
      associated with being female, higher age, long baseline symptom duration, and
      higher baseline pain intensity score; positive DeQuervain test was associated
      with lower probability of persistent symptoms. Having a recurrent problem was
      associated with higher odds of specialist referral. CONCLUSION: In primary care,
      physical tests and information about physical signs are of importance in
      diagnosing patients with hand or wrist problems, but provide limited prognostic
      information.

PMID- 19585390
TI  - Effects of quetiapine on cognitive functions in schizophrenic patients: a
      preliminary single-trial ERP analysis.
AB  - AIM: The study aimed to explore by means of single-trial event-related potentials
      (ERPs), whether and how the medication change from older neuroleptics to
      quetiapine in schizophrenic patients led to a significant cognitive enhancement.
      This single-trial ERP analysis helps to investigate attention and memory
      processes in the single patient before and after treatment. PATIENTS AND METHODS:
      Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up
      for 16 weeks and assessed for changes of clinical symptoms and ERP components
      P300 representing target detection processes and N400 indexing context
      integration in word recognition processes. Three subjects had to be excluded from
      the ERP recording sessions because of excessive blink artefacts and movements.
      RESULTS: Regarding the P300 components of the target detection, there were
      significant increases of amplitudes in 5 of 10 patients (50%) at week 16
      comparing with week 0. Regarding the N400 components of the word recognition,
      there were significant increases of amplitudes in 4 of 10 patients (40%) at week
      16 comparing with week 0. DISCUSSION: The mean scores of PANSS, MADRS, Bf-S, SCL
      90 and CGI-S at the end of study (week 16) showed significant improvements
      compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal
      symptoms as well as akathisia were reported after quetiapine treatment. These
      preliminary data suggest that quetiapine might partially improve the cognitive
      functions in the context integration and target detection processing in these
      patients. This technical procedure (single-trial ERP) may help to differentially
      assess cognitive enhancements in each single patient under treatment.

PMID- 19585391
TI  - Reasons and outcomes of olanzapine dose adjustments in the outpatient treatment
      of schizophrenia.
AB  - INTRODUCTION: Antipsychotic treatment dose adjustments may influence treatment
      outcomes in patients with schizophrenia. METHODS: We analysed data from 4,247
      outpatients with schizophrenia who started olanzapine monotherapy in the 3-year,
      prospective, observational SOHO study to determine factors associated with
      olanzapine dose adjustments and how these impact on treatment effectiveness and
      tolerability. RESULTS: Regression analyses showed an association between changes
      in the Clinical Global Impression (CGI) and olanzapine dose changes: patients
      with a lack of effectiveness were more likely to have their dose increased,
      whereas patients with good treatment response were more likely to have a dose
      decrease. Improvement in tardive dyskinesia was associated with dose increase or
      no change (p=0.034) and worsening of sexual problems was associated with dose
      decrease (p=0.001). Conversely, an increase in olanzapine dose was associated
      with subsequent clinical improvement (CGI), but dose adjustment had no
      significant effects on tolerability outcomes. DISCUSSION: These results indicate
      that psychiatrists tend to modify olanzapine dose according to treatment
      response. Dose increases seem to be associated with a better response to
      treatment and not with a worsening of side-effects.

PMID- 19585392
TI  - COMT Val 158 Met polymorphism is associated with cognitive flexibility in a
      signal discrimination task in schizophrenia.
AB  - BACKGROUND: Associations between the well-known functional single nucleotide
      polymorphism Val (158)Met in the gene encoding catechol- O-methyltransferase
      (COMT) and cognitive do-mains affected in schizophrenia are inconsistent
      regarding directionality and specific impact and call for a more fundamental
      cognitive endophenotype. Recent studies suggest that the COMT genotype
      contributes to cognitive flexibility, a fundamental cognitive ability that
      potentially influences an individual's performance in a variety of other
      neurocognitive tasks. METHODS: We investigated the association between COMT Val
      (158)Met genotype and cognitive flexibility as assessed by signal discrimination
      in the Continuous Performance Test - Identical Pairs version in a cohort of 111
      German schizophrenic patients. RESULTS: COMT genotype was significantly
      associated with signal discrimination index d' in schizophrenia. The Val/Val
      genotype was associated with the highest and the Met/Met genotype with the lowest
      scores; heterozygous individuals displayed an intermediate performance.
      CONCLUSIONS: Our data suggest that allelic variation at the COMT Val (158)Met
      locus may influence signal discrimination capacity in schizophrenia and confirm
      that Val loading, probably due to decreased prefrontal dopamine availability, is
      associated with greater cognitive flexibility, which in turn may influence other
      cognitive measures that have been associated with COMT to date.

PMID- 19585393
TI  - Translation of randomised controlled trial findings into clinical practice:
      comparison of olanzapine and valproate in the EMBLEM study.
AB  - OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and
      valproate-treated patients in an observational study of acute mania with the
      results of a randomised controlled trial (RCT) assessing the same treatments.
      METHODS: EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2
      year, prospective, observational study of health outcomes associated with the
      treatment of mania. Severity of mania and depression were assessed at baseline
      and 6 weeks using the YMRS and the 5-item version of the HAMD, respectively.
      RESULTS: 621 patients were analysed (n=107 valproate, n=514 olanzapine). Both
      groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores,
      with greater mean improvements in the olanzapine compared with the valproate
      group. Olanzapine was associated with more weight gain and less gastrointestinal
      difficulties than valproate. DISCUSSION: The EMBLEM results support those of the
      RCT, which suggest that olanzapine monotherapy seems to be more effective than
      valproate monotherapy in the treatment of acute mania.

PMID- 19585394
TI  - Aripiprazole as an adjunct to clozapine therapy in adolescents with early-onset
      schizophrenia: a retrospective chart review.
AB  - INTRODUCTION: Combination of antipsychotic substances is a therapeutic option
      increasingly applied in patients with schizophrenia, who do not respond to
      antipsychotic monotherapy. Recently, various reports on combination of clozapine
      with aripiprazole in adults have been published. As there is not yet data on
      adolescent patients, we aimed to study the above-mentioned augmentation strategy
      in this population. METHODS: We included 15 patients with schizophrenia from a
      child and adolescent psychiatric department (8 male; mean age 19.3 [SD+/-1.2,
      range 17.2-21.2] years). Patients had been under clozapine treatment, followed by
      aripiprazole augmentation. Retrospectively, patients' medical records were
      reviewed, using a rating scale in analogy to the Clinical Global Impressions
      (CGI) scale. RESULTS: Mean observation time was 11.1 [SD+/-9.7] months. Mean CGI
      Severity scores improved significantly (p=0.003, d=0.76) from 5.3 (baseline) to
      4.5 (endpoint; last observation carried forward (LOCF)). CGI-Improvement scores
      decreased from 3.7 (after 1 month) to 3.3 (endpoint; LOCF) (p=0.212, d=0.45).
      CONCLUSIONS: In adolescents with schizophrenia, aripiprazole augmentation of
      clozapine treatment might be an effective therapeutic strategy. Prospective
      studies for this age group are required to obtain more specific clinical data on
      clinical effectiveness.

PMID- 19585395
TI  - The effects of paroxetine on the pharmacokinetics of paliperidone extended
      release tablets.
AB  - INTRODUCTION: Co-morbid medical and psychiatric conditions are common in
      individuals with schizophrenia. As such, selecting antipsychotic medications with
      a low potential for drug-drug interactions (DDIs) is crucial, as many are
      extensively metabolized by hepatic cytochrome P450 (CYP) isozymes. METHODS: This
      randomized, crossover study examined the effects of paroxetine (a potent CYP2D6
      inhibitor) on the pharmacokinetic parameters of a single dose of the novel
      antipsychotic agent, paliperidone extended-release tablets (paliperidone ER), in
      healthy subjects. RESULTS: The mean C (max) and AUC of paliperidone were slightly
      higher and paliperidone clearance was slightly lower following co-administration
      of paliperidone ER with paroxetine. There was a ratio of geometric treatment
      means of 116.48% for AUC (infinity) [90% CI: 104.49-129.84]. However, the
      increase in total exposure to paliperidone was not considered clinically
      relevant. The incidence of adverse events was lower when subjects received the
      combination of paliperidone ER and paroxetine compared with paroxetine alone.
      DISCUSSION: Results suggest that no clinically relevant pharmacokinetic
      interaction occurs when paroxetine and paliperidone ER are co-administered and,
      therefore, initiation or discontinuation of concomitant treatment with CYP2D6
      inhibiting drugs does not appear to warrant an adjustment in paliperidone ER
      dosage.

PMID- 19585396
TI  - Atypical anorexia in a male patient accompanied by strong obsessive-compulsive
      symptoms successfully treated with naltrexone.

PMID- 19585397
TI  - Aripiprazole for the management of olanzapine-induced weight gain.

PMID- 19585398
TI  - Submaximal fatigue and recovery in boys and men.
AB  - We examined the effects of a sustained submaximal isometric contraction on
      fatigue and recovery rates in untrained prepubescent boys and men. Fifteen
      prepubescent boys and 15 men executed an isometric plantar flexion at 20% of
      their maximal voluntary contraction for 10 min. During the fatigue protocol,
      surface electromyogram of the soleus, medial gastrocnemius, and tibialis anterior
      muscles were obtained. Following the fatigue protocol, maximal voluntary
      contraction data were also obtained every 3 min throughout a 15-min recovery
      period. During the fatigue protocol, agonist and antagonist surface
      electromyogram increased gradually to a similar extent in both groups. Following
      fatigue, torque and surface electromyogram during a maximal voluntary contraction
      decreased compared to pre-fatigue values and recovered in a similar manner in
      both groups. However, boys showed faster recovery in torque and surface
      electromyogram during the third minute of recovery period. It is concluded that a
      low-intensity sustained isometric fatigue protocol induces similar fatigue levels
      in boys and men. However, there is evidence that boys can recover faster than
      men.

PMID- 19585399
TI  - Criterion-related validity of sit-and-reach and modified sit-and-reach test for
      estimating hamstring flexibility in children and adolescents aged 6-17 years.
AB  - The purpose of the present study was to examine the criterion-related validity of
      the sit-and-reach test (SRT) and the modified sit-and-reach test (MSRT) for
      estimating hamstring flexibility in children and adolescents as well as to
      determine whether the MSRT is more valid than the SRT. A total of 87 (45 boys and
      42 girls) children (6-12 years old) and adolescents (13-17 years old) performed
      the SRT and the MSRT. Hamstring flexibility was measured with goniometry through
      the passive straight-leg raise test. Regression analysis was performed to study
      the association of SRT and MSRT with hamstring flexibility (criterion measure).
      The SRT was associated with hamstring flexibility in both children (beta=1.089, R
      (2)=0.281, p=0.001) and adolescents (beta=0.690, R (2)=0.333, p=0.004). The MSRT
      was also associated with hamstring flexibility in both children (beta=1.296, R
      (2)=0.298, p<0.001) and adolescents (beta=0.588, R (2)=0.243, p=0.027). It is
      concluded that the criterion-related validity of the SRT and the MSRT for
      estimating hamstring flexibility is weak. The present data do not support that
      the MSRT is a more valid method than the SRT in children and adolescents.

PMID- 19585400
TI  - Reproducibility of the 6-minute walk test in obese adults.
AB  - The six-minute walk test (6MWT) is an inexpensive, quick and safe tool to
      evaluate the functional capacity of patients with heart failure and chronic
      obstructive pulmonary disease. The aim of this study was to determine the
      reproducibility of the 6MWT in overweight and obese individuals. We thus
      undertook a prospective repeated-measure validity study taking place in our
      academic weight management outpatient clinic. The 6MWT was conducted twice the
      same day in 21 overweight or obese adult subjects (15 females and 6 males).
      Repeatability of walking distance was the primary outcome. Anthropometric
      measures, blood pressure and heart rate were also recorded. Participant's mean
      BMI was 37.2+/-9.8 kg/m(2) (range: 27.0-62.3 kg/m(2)). Walking distance in the
      morning (mean=452+/-90 m) and in the afternoon (mean=458+/-97 m) were highly
      correlated (r=0.948; 95% Confidence Interval 0.877-0.978; p<0.001). Walking
      distance was negatively correlated with BMI (r=-0.47, p=0.03), waist
      circumference (r=-0.43, p=0.05) and pre-test heart rate (r=-0.54, p=0.01). Our
      findings indicate that the 6MWT is highly reproducible in obese subjects and
      could thus be used as a fitness indicator in clinical studies and clinical care
      in this population.

PMID- 19585401
TI  - Resistance training in cancer survivors: a systematic review.
AB  - This systematic review summarizes the research of previous studies that used
      resistance training in the post-treatment phase of cancer patients with a focus
      on methodological quality, training methods and physical outcome measures. We
      found twenty-four studies (10 RCTs, 4 controlled clinical trials and 10
      uncontrolled trials) that met all inclusion criteria. The studies were of
      moderate methodological quality. The majority of studies involved breast cancer
      patients (54%), followed by prostate cancer patients (13%). Most studies used a
      combination of resistance and aerobic training, which was mostly supervised.
      Resistance training involved large muscle groups, with 1-3 sets of 8-12
      repetitions. The duration of the resistance training programs varied from 3-24
      weeks, with a training frequency of 1-5 sessions per week. The training intensity
      ranged from 25% to 85% of the one-repetition maximum. Overall, positive training
      effects were observed for cardiopulmonary and muscle function, with significant
      increases in peak oxygen uptake (range: 6-39%), and in the one-repetition maximum
      (range: 11-110%). In general, there were no effects of training on body
      composition, endocrine and immune function, and haematological variables. No
      adverse effects of the resistance training were reported. Based upon these
      results, we recommend to incorporate resistance training in cancer rehabilitation
      programmes.

PMID- 19585402
TI  - Kinematic analysis of volleyball spike jump.
AB  - The purpose of this study was to determine the influence of upper and lower
      extremity movements on the volleyball spike jump (SJ) and how this movement may
      differ from the standing vertical jumps due to its asymmetry. The 3-D kinematics
      of body segments were measured in 16 experienced volleyball players with a VICON
      motion capture system. The jump heights (JH) of counter-movement (CM) and SJ were
      determined utilizing a force platform. A significant correlation was found
      between the JH during the SPJ and the maximal horizontal velocity of the center
      of mass (CoM) (r=0.71, p=0.002), the minimum height of the CoM (r=-0.68,
      p=0.004), the JH during CMJ (r=0.66, p=0.006) and SJ (r=0.74, p=0.001), the range
      of movement of right knee flexion-extension (r=0.76, p=0.001) and the angular
      velocity of left shoulder hyperextension (r=0.72, p=0.002). The asymmetry of the
      SJ revealed differences in angles, angular velocities of the right and left legs
      and arms, and a significant difference (p=0.001) between the distances of the
      left and right foot center to the CoM. Results of our study suggest the
      importance of optimal approach technique to reach a maximal JH in the volleyball
      SJ. The SJ movement is influenced by general jumping ability.

PMID- 19585403
TI  - The core and hip in soccer athletes compared by gender.
AB  - Gender differences in hip and core strength and range of motion may contribute to
      the gender based variance in injury risk. This study was designed to test the
      primary hypothesis that hip and core strength, flexibility and lower extremity
      dynamic alignment differ in male and female soccer athletes. Ninety-eight
      collegiate soccer players (54 male, 44 female) participated in this study.
      Athletes were evaluated for hip range of motion, and hip and abdominal strength.
      Both male and female soccer players demonstrated limited hip rotation, with less
      hip internal rotation in males (p<0.0001), and poor abdominal core control,
      although the males are stronger (p=0.02). Overall hip ROM is shifted towards
      internal rotation in females compared to males. Female soccer players also have a
      significant side-to-side disparity in hip abductor strength (p<0.0001), not
      present in males. The shift in hip ROM towards internal rotation combined with
      the hip abductor imbalance may be associated with a position of ACL risk with
      internally rotated hips and valgus knees in female soccer players. Limitations in
      hip and core strength and range of motion may play a role in the disparity
      between the male and female rate of ACL injury.

PMID- 19585404
TI  - Qualitative in vitro NMR analysis of creatine ethyl ester pronutrient in human
      plasma.
AB  - There are a number of forms of creatine available that attempt to improve the
      solubility and permeability, with the anticipation this will result in an
      improved pharmacokinetic profile and ultimately an enhanced ergogenic response.
      Previous research has shown that the different salt forms can improve solubility
      resulting in slightly altered pharmacokinetic profiles, however specific data
      exploring the conversion of esterified derivatives to creatine is lacking. The
      purpose of this study was to examine the assertion that creatine ethyl ester
      undergoes enzymatic conversion to creatine in human tissues. The IN VITRO
      response of creatine ethyl ester to incubation in human plasma was examined by H
      NMR analysis. Lyophilized human plasma was reconstituted in D2O and phosphate
      buffered saline and 1.5 mg of the analyte was added. Following incubation at 37
      degrees C for 4 h and subsequent protein precipitation, the supernatant was
      analyzed by NMR, utilizing the diagnostic chemical shift of the methylene signal
      to determine the species present in solution, I.E. creatine ethyl ester,
      creatine, or creatinine. Both creatine and creatinine were run in parallel as
      control experiments and each assay was run in triplicate. As expected both
      creatine and creatinine remained unchanged. However, conversion of creatine ethyl
      ester to creatine by the esterases in human plasma was not observed to any
      detectable extent and the only species detected after the incubation period was
      creatinine. While not a definitive characterization of the IN VIVO behavior,
      these results strongly warrant a complete IN VIVO pharmacokinetic analysis of
      creatine ethyl ester since it appears these "pronutrients" may actually provide
      large exogenous sources of pharmacologically inactive creatinine rather than
      ergogenic creatine.

PMID- 19585405
TI  - Phosphorylation of perilipin is associated with indicators of lipolysis in
      Holstein cows.
AB  - Perilipin is a regulatory protein that coats the lipid droplet in adipocytes. In
      the basal state, perilipin inhibits lipolysis by restricting access of hormone
      sensitive lipase (HSL) to the lipid droplet. In contrast, during stimulated
      lipolysis, phosphorylated perilipin interacts with HSL such that the catalytic
      activity of HSL on its acylglycerol substrate is enhanced. However, the
      regulation and function of perilipin in vivo has not been defined clearly across
      comparative animal models. Consequently, this study was undertaken to determine
      if changes in perilipin mRNA, protein, or phosphorylation state are associated
      with in vivo indicators of lipolysis in the dairy cow as a model of lipolysis
      induced by the marked metabolic demands of lactation. Semiquantitative western
      blotting and quantitative PCR were used to quantify total and phosphorylated HSL
      and perilipin in adipose tissue obtained from cows in early [5-14 days in milk
      (DIM), n=11] and mid (176-206 DIM, n=9) lactation. As expected, circulating NEFA
      and glycerol concentrations, and phosphorylated HSL were greater in early versus
      mid lactation, indicative of greater lipolytic activity in early lactation.
      Furthermore, phosphorylated, but not total perilipin abundance, was greater in
      early lactation when the metabolic demand for energy is greater than in mid
      lactation. Finally, the abundance of phosphorylated perilipin was positively
      correlated with circulating glycerol and NEFA concentrations during both early
      and mid lactation. Collectively, these data support the hypothesis that
      phosphorylated perilipin is a critical determinant of lipolytic activity stemming
      from the metabolic demands of lactation.

PMID- 19585406
TI  - Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol
      in saliva and serum in comparison with the insulin tolerance test.
AB  - Unstimulated early morning cortisol has been suggested as a first line parameter
      to assess adrenal function in patients with suspected secondary adrenal
      insufficiency. The measurement of basal salivary cortisol (BSaC) instead of basal
      serum cortisol (BSeC) offers some advantages, such as painless sampling and the
      determination of the free hormone. The objective of this study was to evaluate
      the diagnostic value of BSeC and BSaC in comparison to the insulin tolerance test
      (ITT). Seventy-seven patients with hypothalamic-pituitary disease and 184 healthy
      controls were enrolled. ITT were performed in patients, and BSeC as well as BSaC
      levels were measured in patients and controls. Upper and lower thresholds (with
      >or=95% specificity either for adrenal sufficiency or adrenal insufficiency) were
      calculated by ROC analysis both for BSeC and BSaC. The ITT identified 41 patients
      as adrenal insufficient and 36 patients as adrenal sufficient. Upper and lower
      cutoffs were 470 and 103 nmol/l for BSeC, and 21.1 and 5.0 nmol/l for BSaC,
      respectively. Thereby, basal cortisol allowed a highly specific diagnosis (i.e.,
      similar to the ITT result) in either 23% (BSeC) or 27% (BSaC) of patients. We
      suggest the determination of unstimulated early morning cortisol as first-line
      screening method for the diagnosis of secondary adrenal insufficiency. If upper
      and lower cutoffs are used, dynamic testing could be obviated in about one fourth
      of cases. Due to its easy and painless collection BSaC may be preferable to BSeC.

PMID- 19585407
TI  - Effect of testosterone on thyroid weight and function in iodine deficient
      castrated rats.
AB  - The prevalence of goiter, especially in iodine deficient regions, is higher in
      women than in men. This investigation was conducted to determine the effect of
      testosterone on thyroid weight and function in both normal iodine deficient and
      castrated rats. Male Wistar rats were divided into 6 groups of 7 animals each:
      castrated hormone treated (C+T); castrated nonhormone treated (C+NT); normal (N),
      iodine deficient diet, castrated hormone treated (ID+C+T); castrated iodine
      deficient diet, nonhormone treated (ID+C+NT); and normal iodine deficient diet
      (ID+N). Three weeks after castration, C+T and ID+C+T groups received daily
      intraperitoneal injections of 1 mg/kg testosterone enanthate, for 9 weeks. At the
      end, we measured thyroid weight and serum testosterone, T(4), free T(4), T3, and
      TSH, and urinary iodine concentrations. Serum testosterone level significantly
      decreased in the C+NT and ID+C+NT groups (p<0.001). In ID groups, serum TSH, T(3)
      and thyroid weight levels increased significantly and serum T4 and free T (4)
      levels decreased significantly as compared to iodine sufficient groups (p<0.001).
      ID+C+NT group, had higher serum TSH and thyroid weight and lower serum-free T4
      than the ID+C+T and ID+N groups (p<0.01). The C+NT group had higher serum TSH and
      lower serum-free T(4) than the C+T and N groups (p<0.01). These results suggest
      that testosterone decreases thyroid enlargement and prevents the fall in free
      T(4) levels in ID castrated rats, which may explain the lower incidence of goiter
      in men than women in iodine deficient regions.

PMID- 19585408
TI  - [Academic plastic surgery: a comparison of residency models in Germany and the
      USA].
AB  - In this review article, the current postgraduate training programs in plastic
      surgery in Germany and the USA are compared with regard to structure, methods,
      duty hours, income, board examination and research opportunities.

PMID- 19585409
TI  - Paediatric surgical complications of Ehlers-Danlos syndrome.

PMID- 19585410
TI  - [The English patient].

PMID- 19585415
TI  - Current status of venous thromboembolism prophylaxis.
AB  - Postoperative venous thromboembolism (VTE) represents a serious and potentially
      fatal complication that affects 40% to 60% of patients undergoing major
      orthopedic surgery and not receiving antithrombotic prophylaxis. Several
      prophylactic modalities, including pharmacological agents such as oral vitamin K
      antagonists (VKA) and low molecular weight heparins (LMWH), have been shown to be
      effective and safe for most patients at high risk for VTE. However, some patients
      undergoing cancer or major orthopedic surgery remain at some residual VTE risk
      despite the use of these methods. Approaches to improve the results of
      prophylaxis include optimizing the timing and duration of pharmacological
      prophylaxis, combining mechanical methods with anticoagulants, and the
      development of new antithrombotics.

PMID- 19585419
TI  - Minimally invasive Ivor Lewis esophagectomy for the management of iatrogenic
      esophageal perforation in a patient with esophageal cancer.
AB  - Esophageal perforation after endoscopic instrumentation is a surgical emergency.
      Prompt diagnosis and treatment have a significant impact on mortality. In the
      setting of esophageal cancer, iatrogenic perforation presents a difficult
      challenge for surgical management as primary repair is not feasible. In this
      chapter, we describe the use of a minimally invasive Ivor Lewis esophagectomy for
      the management of an iatrogenic esophageal perforation in a patient with
      metastatic esophageal cancer.

PMID- 19585431
TI  - Single-center retrospective study of the technique, safety, and 12-month efficacy
      of the MiniArcTM single-incision sling: a new minimally invasive procedure for
      treatment of female SUI.
AB  - This study was conducted to report on the technique, safety, and early efficacy
      of a single-incision mini-sling to treat female stress urinary incontinence
      (SUI). Women suffering from SUI were offered a single-incision approach to place
      a suburethral polypropylene mesh tape in a position similar to that of a
      transobturator sling without passage of needles through the groin. Retrospective
      data was collected on 61 patients that received the new MiniArcTM single-incision
      sling at a single center in the United States. Patient selection and concomitant
      procedures were determined by the senior authors at the center, and the senior
      authors were the primary surgeons in all cases. Procedures were completed under
      general, regional, or MAC anesthesia as determined by the surgeon. Average
      operative time for the sling procedure alone was short and the average blood loss
      was 29 cc. There were no intraoperative complications. There was one
      postoperative adverse event secondary to urinary retention that was resolved by
      loosening of the sling under local anesthesia in an office setting. The overall
      cure rate at 12 months determined by physician and patient assessment in 58/61
      patients was 91.4%. No patients suffered pain or dyspareunia secondary to the
      sling, and no erosions or extrusions were reported. In this initial study, the
      MiniArcTM single-incision sling appears to be a safe approach to treat female
      SUI, and the early clinical results are encouraging.

PMID- 19585438
TI  - Vertical expandable prosthetic titanium rib (VEPTR): indications, technique, and
      management review.
AB  - Surgical correction is generally indicated as the primary form of management in
      children with severe early onset scoliosis. Even so, conservative, nonsurgical
      treatment is always considered first, as surgical correction carries significant
      concomitant consequences, including but not limited to crankshaft phenomenon and,
      more importantly, inhibition of further spine, lung, and chest growth in
      skeletally immature patients. Fusionless surgical procedures assuage some of
      these risks, as they are characteristically associated with techniques
      necessitating spinal fusion. One device looks particularly promising in treating
      and managing severe early onset scoliosis, the vertical expandable prosthetic
      titanium rib (VEPTR)-a device that was initially targeted toward children with
      thoracic insufficiency syndrome (TIS). Despite its promising results in
      correction of severe early onset scoliosis, as well as associated rib and chest
      wall deformities, the VEPTR nevertheless has a complication rate comparable to
      other fusionless techniques. Continued modifications and research will hopefully
      beget a device that permits thoracic and spinal growth in skeletally immature
      patients yet with fewer postoperative complications. In this chapter, the authors
      review the clinical experience with VEPTR to date and present their results in 16
      children with congenital scoliosis cared for at Shriners Hospital of
      Philadelphia.

PMID- 19585439
TI  - [Management of venous thromboembolism].

PMID- 19585440
TI  - [CME--Ultrasound diagnosis 29. High echo formations in the kidneys].

PMID- 19585441
TI  - [Epidemiology of chronic venous insufficiency--Swiss survey with surprising
      results].
AB  - Lower limb chronic venous insufficiency (CVI) is one of the most common diseases
      in western world adults with considerable socio-economic impact. Varicose veins
      of the legs are caused by a number of factors. Current data suggest that both
      lifestyle and environmental factors play a role in varicose vein occurrence.
      Nevertheless, environmental factors seem to play greater role than previously
      thought. This was also observed in a Swiss survey of 1099 participants carried
      out during summer 2008 in 40 different Swiss pharmacies.

PMID- 19585442
TI  - [Ethical problems in clinical practice of evidence-based medicine].
AB  - Ethical problems as consequences of evidence-based medicine (EBM) have
      insufficiently been investigated and discussed. EBM--as initially intended--is
      usually interpreted as an attempt to treat patients individually with respect to
      their personal preferences and the present situation according to the best
      available clinical evidence. This practice is in line with accepted medical
      ethics. Therefore, it does not appear to be a relevant issue for discussion at
      first sight. However, between the theoretical concept and the practical use (or
      misuse) of this approach discrepancies exist which require some considerations.
      In particular the practical use of EBM generates a number of ethical problems:
      EBM is increasingly misused as an instrument of resource-allocation. Based on
      randomized controlled trials (RCTs) for very specific patient groups, the general
      access to medical supply is regulated and limited. The recurrence to general
      ("supra-individual") external evidence may additionally be in strong contrast to
      the individual patients' intentions and will and leads to conflicts for therapy
      decisions. If no longer the individual preferences and the patients' will are in
      the center of therapy decisions but a so called "general welfare", the mutual
      trust between patient and doctor is eroded. The utilitaristic approach of a
      primacy of this general welfare in opposition to the individual welfare is
      favored by the present interpretation and use of EBM. This conflicts with the
      perception of the doctor as a patient's advocate. However, the doctor being the
      patient's advocate is the basis of the traditional medical ethos. We should take
      care that we do not completely lose the basis of our medical ethos.

PMID- 19585443
TI  - [Acute psychosis caused by co-amoxiclav].

PMID- 19585444
TI  - [18-year-old woman with an ovarian tumour detected by coincidence].
AB  - Massive ovarian edema (MOE) is a rare, benign disease of young women. Because
      preoperatively in most cases the differential diagnosis primarily appears to
      indicate the presence of a malignant tumour, there is a risk that these patients
      will be subjected to unnecessary overtreatment. In the case of the 18-year-old
      patient described here, on the basis of the preoperative data the suspected
      clinical diagnosis was polycystic ovarian (PCO) syndrome. In the MRI the enlarged
      ovary was interpreted as a mucous tumour. The laparotomy showed a smooth-walled,
      opalescent ovarian tumour with adnexal torsion. Histopathological examination of
      the adnexectomy specimen gave the diagnosis of a massive ovarian edema (MOE).
      Therapeutically, a wedge-shaped excision, immediate-section histology and
      derotation and suspension of the ovary would have been sufficient. Unnecessary
      overtreatment can be avoided in young women with enlarged ovaries, if MOE is
      included in the differential diagnosis and if the characteristic sonography, MRI
      and macroscopy findings are known.

PMID- 19585451
TI  - [Physician--sculptures and literature puzzle].

PMID- 19585445
TI  - [Headaches and aphasia in an immunocompromised patient].
AB  - We report the case of a 81-year-old, immunocompromised Patient, admitted to our
      hospital with new-onset headaches and word-finding difficulties. The MRI of the
      brain revealed a temporal mass on the left with marginal contrast-enhancement.
      During the next days Listeria monocytogenes grew in the bloodcultures so that the
      diagnosis of a brain-abscess caused by Listeria was established. Due to the
      localisation, surgical drainage of the abscess was not possible, so that a
      prolonged antibiotic therapy lasting over 4.5 months was initiated. The MRI after
      therapy demonstrated no abscess persistence. Listeria mostly cause infections in
      the immunocompromised, elderly, newborn or pregnant host. Next to bacteraemia
      without a focus, CNS-invasion with meningitis, meningoencephalitis or less
      frequent abcess-formation (5-10%) is the most important manifestation.

PMID- 19585454
TI  - Biodistribution of two (131)I-IMBA preparations, differently labelled, in mice
      with experimental B16 melanoma tumours.
AB  - BACKGROUND: Numerous reports indicate that some iodinated compounds of benzamide
      derivatives display a strong affinity to the cells of melanoma. In the present
      report, a compound [N-(2-diethylaminoethyl)-3-iodo-4metyoxybenzamide ((131)I
      IMBA)] has been prepared by two different labelling methods. Biodistribution of
      the injected compound was followed in mice with experimentally induced B16
      melanoma tumours, and tumour/ tissue ratios were studied as a function of time
      post administration. MATERIAL AND METHODS: The iodinated (131)I-IMBA was obtained
      by means of (131)I exchange for nonradioactive iodine atoms (method I) and by
      means of (131)I substitution for a metalorganic group (method II). The last
      preparation was purified by chloroform extraction. The chemical purity was
      assessed by means of ascending thin layer chromatography (TLC). The
      biodistribution of (131)I-IMBA in C57 Black mice was studied in animals with
      experimentally induced B16 mice melanoma tumours. RESULTS: The mean labelling
      efficiency exceeded 95 and 80 % for methods I and II, respectively, at
      radiochemical purity > 95% in both cases. (131)I-IMBA was vividly cumulated by
      melanoma tumours in mice. At 24-hours post (131)I-IMBA administration the values
      of tumour /non-tumour ratios for the compound labelled by method II reached the
      following values: tumour/liver 10 +/- 3, tumour/lung 15 +/- 12, tumour/blood 153
      +/- 39, tumour/intestines 176 +/- 26, tumour/kidneys 270 +/- 107, and
      tumour/muscle 448 +/- 82. These values exceeded, by an order of magnitude, the
      corresponding ratios for the same compound labelled by method I. CONCLUSIONS:
      High values of tumour/non-tumour ratios indicate that (131)I-IMBA could be a
      promising radiopharmaceutical for clinical diagnosis (staging) of melanomas in
      humans.

PMID- 19585453
TI  - Preparation and evaluation of [(61)Cu]-thiophene-2-aldehyde thiosemicarbazone for
      PET studies.
AB  - BACKGROUND: [(61)Cu]Thiophene-2-aldehyde thiosemicarbazone ([(61)Cu]TATS) (4) was
      prepared according to an analogy of carrier copper compound with antitumor
      activity, for eventual use in PET. MATERIAL AND METHODS: [(61)Cu]TATS was
      prepared using copper-61 acetate and in-house made ligand (TATS) in one step.
      (61)Cu was produced via the (nat)Zn(p,x) (61)Cu nuclear reaction (180 mircoA, 22
      MeV, 3.2 h) followed by a two-step chromatography method (222 GBq of (61)Cu(2+)).
      [(61)Cu]TATS preparation was optimized for reaction conditions (buffer
      concentration and temperature). The tracer was finally administered to normal
      rats for biodistribution studies. RESULTS: Total radiolabelling of the tracer
      took 30 minutes with a radiochemical purity of more than 90% (using HPLC and
      RTLC) and specific activity of about 250-300 Ci/mmol. The complex was stable in
      the presence of human serum for an hour. The biodistribution of copper cation and
      the tracer was checked in wild-type rats for up to 2 hours with significant
      spleen and lung uptake of the tracer. CONCLUSIONS: The production of (61)Cu via
      the (nat)Zn(p,x) (61)Cu is an efficient and reproducible method with high
      specific activity leading to the production and preliminary evaluation of
      [(61,)Cu]TATS, a potential PET tracer, was reported.

PMID- 19585456
TI  - Effect of attenuation correction on normal (99)mTc-MIBI myocardial perfusion
      scintigrams acquired with a hybrid SPECT/CT camera.
AB  - The aim of this study was to evaluate the effect of the CT-derived attenuation
      correction on (99m)Tc-MIBI normal myocardial perfusion scintigrams. Rest
      perfusion scintigrams of patients in whom coronary artery disease was suspected,
      without a history or any signs in ECG of a myocardial infarction, were analysed.
      Patients were included in the material if their rest perfusion scintigrams were
      normal. This criterion was fulfilled by 61 patients (29 men and 32 women) aged
      between 40 and 74 (mean value 57) years, with body mass between 50 and 120 (mean
      value 70) kg. Tomographic reconstruction of a radionuclide study was performed
      with an iterative OSEM method (10 subsets, 2 iterations) sequentially without and
      with attenuation and scatter corrections on a dedicated Xeleris workstation,
      applying an ACQC tool to enable manual realignment of SPECT and CT images. SPECT
      studies were evaluated visually and semiquantitatively. Visual analysis of
      tomograms was performed with the aim of finding sites of significantly lower
      counts in comparison with the maximal level (in the lateral wall).
      Semiquantitative analysis was based on counts in 20 segments of a polar map.
      Attenuation correction caused a complete (in 32 of 40 - 80% of patients) or
      partial (in 8 of 40 - 20% of patients) filling out of all areas of lower counts
      in the inferior wall. However, although in the anterior wall attenuation
      correction caused a complete (in 11 of 35 - 31% of cases) or partial (10 of 35 -
      29% of cases) filling of areas of lower counts, in 14 cases (40%) those areas
      remained unchanged or increased, and in 8 cases (13% of all patients) new areas
      of decreased counts appeared. The same was true for the apical region, in which
      areas of decreased counts were detected in 14 of 61 (23%) cases without
      attenuation correction, but after application of the correction number of apical
      defects, this figure grew to 22 (36%) patients. Altogether, attenuation
      correction reduced the total number of lower count areas from 104 to 66. Semi
      quantitative analysis revealed that attenuation correction reduced nonuniformity
      in counts in the whole myocardium - the mean difference between segment with
      maximum counts and values in all segments was reduced from 17.5 +/- +/- 12% to
      11.0 +/- 10.3% (p < 0.0001) in male patients, and in female patients, from 11.5
      +/- 9% to 10.5 +/- 8.6%, thus equalling non-uniformities in myocardial
      scintigrams of both sexes. Misalignment of CT and SPECT studies was observed in
      17 (28%) patients but only in 2 (3% of all patients) patients did CT realignment
      evidently change the attenuation corrected scintigrams. Although attenuation
      correction can cause artefacts, its use is justified by the reduction of the
      total number of areas of lower counts and the improvement of uniformity of images
      of normally perfused myocardium.

PMID- 19585455
TI  - Impact of CT based attenuation correction on quantitative assessment of DaTSCAN
      ((123)I-Ioflupane) imaging in diagnosis of extrapyramidal diseases.
AB  - The quality of visually and semi-quantitatively assessed DaTSCAN images is
      crucial for differential diagnostics of extrapyramidal diseases. Neuroimaging
      with the use of presynaptic tracers of the dopaminergic system provides evidence
      of nigrostriatal degeneration and may support the clinical diagnosis of
      Parkinsonism. During the last two years (2007-2008) we tried to elaborate the
      optimal methodology of SPECT/CT examination with the use of DaTSCAN ((123)I
      Ioflupane), and we sought to evaluate the effect of the reconstruction and
      attenuation correction method on semi-quantitative measures of relative uptake in
      the striatum. In a present study, we retrospectively studied DaTSCAN scans of 44
      consecutive patients with clinical indications of Parkinson's disease or
      uncertain Parkinsonian syndromes. The quality of DaTSCAN images reconstructed
      with the use of ordered-subset expectation maximization reconstruction technique
      (OSEM) with attenuation correction based on CT maps was found to be superior to
      that provided by the commonly applied filtered backprojection method (FBP) with
      Chang attenuation correction. OSEM reconstructed transverse slices were more
      legible for clinical interpretation because of increased contrast and improved
      delineation between striatum structures. Semi-quantitative assessments of
      relative striatum uptake for OSEM reconstructed slices secured better intra
      operator reproducibility than that obtained by FBP method.

PMID- 19585458
TI  - Detection of bilateral, multifocal breast cancer and assessment of tumour
      response to neoadjuvant chemotherapy by Tc-99m sestamibi imaging - a case report.
AB  - In breast cancer, neoadjuvant chemotherapy needs early indication for
      responsiveness. Tc-99m sestamibi scintimammography provides comprehensive
      information about the extent of disease including multiple foci in one or both
      breasts and possible involvement of nodes. In the present case, X-mammography was
      positive for a suspicious mass in the upper quadrant of the left breast only. On
      the other hand,Tc-99m Sestamibi scintimammography was able to depict the full
      extent of the disease, including its spread to the axillary lymph node, and gave
      useful information on the effectiveness of neoadjuvant chemotherapy. The case
      reported here demonstrates that Tc-99m sestamibi scintimammography was useful in
      detecting bilateral breast cancer and could provide additional information on
      possible axillary lymph node involvement. Furthermore, Tc-99m sestamibi
      scintimammography was effective in monitoring response to chemotherapy in the
      studied case.

PMID- 19585457
TI  - Age-related changes in skull uptake on bone scintigraphy: a quantitative study.
AB  - BACKGROUND: "Hot skull", or diffuse increased activity of bone seeking
      radiotracers, is frequently seen in the bone scans of some patients, especially
      elderly women. This finding has been attributed to enhanced bone metabolism in
      old age. MATERIAL AND METHODS: We semi-quantitatively studied 342 normal bone
      scans (161 male and 181 female within the age range 12 to 82 years). We divided
      the patients into 7 age groups: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, and 70
      and above. The geometric means of the anterior and posterior background corrected
      skull and mid-femoral ROI values were used for calculation of the skull to
      femoral ratio (SFR). RESULTS: The skull to femoral ratio was significantly higher
      in female patients in the age groups 30-39 and above. In females, the five upper
      age groups (30-39, 40-49, 50-59, 60-69, and 70 and above) had significantly
      higher SFR than the lower age groups. In males, the two upper age groups (60-69,
      70 and above) had significantly higher SFR than the lower age groups. The
      findings in males were not concordant with the previous studies addressing this
      issue, which could be explained by different bone mineral density in the Iranian
      population. CONCLUSION: Our data showed that "hot skull" is not necessarily an
      abnormal finding, especially in elderly women. We suggest that every nuclear
      medicine department uses its own normal values and reference samples for
      quantitative evaluation, due to ethnic or socio-economical variations.

PMID- 19585459
TI  - Neurolymphomatosis detected by (18)F-FDG PET/CT scan - a case report.
AB  - Lymphoma involvement of the peripheral nerves is a rare clinical presentation of
      non-Hodgkin lymphoma. We report the case of a 59-year-old woman with the defect
      of peripheral motor neuron admitted for PET/CT scan. The scan disclosed increased
      (18)F-FDG activity along the brachial and lumbar plexuses together with very
      intense (18)F-FDG uptake in the cervical lymph node masses. The diagnosis, based
      on the subsequent histopathologic lymph node examination, was diffuse large B
      cell lymphoma.

PMID- 19585460
TI  - Cryopreservation of dissociated human embryonic stem cells in the presence of
      ROCK inhibitor.
AB  - Two different methods have been adopted for the cryopreservation of human
      embryonic stem cells (hESCs): vitrification and conventional slow freezing/rapid
      thawing. However, these methods present poor viability and high differentiation
      rates. Therefore, the development of an efficient cryopreservation protocol for
      hESCs is one of the major challenges for the application of these cells in
      clinical therapy and regenerative medicine. A novel method for the
      cryopreservation of dissociated hESCs in the presence of a selective Rho
      associated kinase (ROCK) inhibitor that increases cell survival and the
      efficiency of colony formation of cryopreserved hESCs has been developed.
      Moreover, this protocol improves the existing methods presenting short recovery
      times and hardly any differentiation rates. Thus, an easy handling protocol that
      allows the cryopreservation of large amounts of hESCs is described.

PMID- 19585461
TI  - Differentiation of embryonic stem cells into anterior definitive endoderm.
AB  - Anterior definitive endoderm (ADE) is both an important embryonic signaling
      center and a unique multipotent precursor of liver, pancreas, and other visceral
      organs. Here we describe a method for the differentiation of mouse embryonic stem
      (ES) cells to endoderm with pronounced anterior character. ADE-containing
      cultures can be produced in vitro by suspension (aggregation or embryoid body)
      culture and in a serum-free adherent monolayer culture. Purified ES cell-derived
      ADE cells appear committed to endodermal fates and can undergo further
      differentiation in vitro towards liver and pancreas with enhanced efficiency.

PMID- 19585462
TI  - Assessing cumulative incidence functions under the semiparametric additive risk
      model.
AB  - In analyzing competing risks data, a quantity of considerable interest is the
      cumulative incidence function. Often, the effect of covariates on the cumulative
      incidence function is modeled via the proportional hazards model for the cause
      specific hazard function. As the proportionality assumption may be too
      restrictive in practice, we consider an alternative more flexible semiparametric
      additive hazards model of (Biometrika 1994; 81:501-514) for the cause-specific
      hazard. This model specifies the effect of covariates on the cause-specific
      hazard to be additive as well as allows the effect of some covariates to be fixed
      and that of others to be time varying. We present an approach for constructing
      confidence intervals as well as confidence bands for the cause-specific
      cumulative incidence function of subjects with given values of the covariates.
      Furthermore, we also present an approach for constructing confidence intervals
      and confidence bands for comparing two cumulative incidence functions given
      values of the covariates. The finite sample property of the proposed estimators
      is investigated through simulations. We conclude our paper with an analysis of
      the well-known malignant melanoma data using our method.

PMID- 19585463
TI  - Selective and non-selective non-steroidal anti-inflammatory drugs and the risk of
      acute kidney injury.
AB  - PURPOSE: Use of non-steroidal anti-inflammatory drugs (NSAID) is associated with
      risk of acute kidney injury (AKI). Risk of AKI may vary with selectivity of the
      NSAID, but this has not been studied in a large cohort where AKI was assessed
      directly from laboratory data. The objective was to compare AKI risk between
      selective and non-selective NSAIDs using a laboratory-based definition of AKI.
      METHODS: We conducted a retrospective nested case-control study in the U.S.
      Department of Veterans Affairs health care system. From a cohort of 1 459 271 new
      NSAID users, we identified 22 824 cases of AKI (97% male; mean age: 63 years),
      and 336 734 matched controls between 2000 and 2006. AKI was defined as a
      creatinine increase of greater than 50%. RESULTS: We found higher risk of AKI in
      new users of any single NSAID (adjusted odds ratio = 1.82; 95%CI: 1.68, 1.98)
      compared to non-users without recent use. The risk of AKI varied among different
      NSAIDs with risk generally increasing with decrease in selectivity: rofecoxib
      (0.95; 0.64, 1.42), celecoxib (0.96; 0.63, 1.47), meloxicam (1.13; 0.63, 2.05),
      etodolac (1.31; 1.08, 1.59), diclofenac (1.11; 0.84, 1.48), piroxicam (1.53;
      1.05, 2.23), salsalate (1.51; 1.22, 1.87), sulindac (1.61; 1.12, 2.30), ibuprofen
      (2.25, 2.04, 2.49), naproxen (1.72; 1.52, 1.95), high dose aspirin (3.64; 2.46,
      5.37), indomethacin (1.94; 1.56, 2.42), keterolac (2.07; 1.78, 2.41). Those using
      multiple NSAIDs appeared to have higher risk (2.90; 2.62, 3.22). CONCLUSIONS:
      This study provides evidence that risk of AKI may be lower with more selective
      agents than with naproxen or other non-selective NSAIDs.

PMID- 19585464
TI  - Insights into the anthrax lethal factor-substrate interaction and selectivity
      using docking and molecular dynamics simulations.
AB  - The anthrax toxin of the bacterium Bacillus anthracis consists of three distinct
      proteins, one of which is the anthrax lethal factor (LF). LF is a gluzincin Zn
      dependent, highly specific metalloprotease with a molecular mass of approximately
      90 kDa that cleaves most isoforms of the family of mitogen-activated protein
      kinase kinases (MEKs/MKKs) close to their amino termini, resulting in the
      inhibition of one or more signaling pathways. Previous studies on the crystal
      structures of uncomplexed LF and LF complexed with the substrate MEK2 or a MKK
      based synthetic peptide provided structure-activity correlations and the basis
      for the rational design of efficient inhibitors. However, in the crystallographic
      structures, the substrate peptide was not properly oriented in the active site
      because of the absence of the catalytic zinc atom. In the current study, docking
      and molecular dynamics calculations were employed to examine the LF-MEK/MKK
      interaction along the catalytic channel up to a distance of 20 A from the zinc
      atom. This residue-specific view of the enzyme-substrate interaction provides
      valuable information about: (i) the substrate selectivity of LF and its
      inactivation of MEKs/MKKs (an issue highly important not only to anthrax
      infection but also to the pathogenesis of cancer), and (ii) the discovery of new,
      previously unexploited, hot-spots of the LF catalytic channel that are important
      in the enzyme/substrate binding and interaction.

PMID- 19585466
TI  - Central nervous system medication use and incident mobility limitation in
      community elders: the Health, Aging, and Body Composition study.
AB  - PURPOSE: To evaluate whether CNS medication use in older adults was associated
      with a higher risk of future incident mobility limitation. METHODS: This 5-year
      longitudinal cohort study included 3055 participants from the health, aging and
      body composition (Health ABC) study who were well-functioning at baseline. CNS
      medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and
      antidepressants) was determined yearly (except year 4) during in-home or in
      clinic interviews. Summated standardized daily doses (low, medium, and high) and
      duration of CNS drug use were computed. Incident mobility limitation was
      operationalized as two consecutive self-reports of having any difficulty walking
      1/4 mile or climbing 10 steps without resting every 6 months after baseline.
      Multivariable Cox proportional hazard analyses were conducted adjusting for
      demographics, health behaviors, health status, and common indications for CNS
      medications. RESULTS: Each year at least 13.9% of participants used a CNS
      medication. By year 6, overall 49% had developed incident mobility limitation. In
      multivariable models, CNS medication users compared to never users showed a
      higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR)
      1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk
      were seen in analyses examining dose- and duration-response relationships.
      CONCLUSIONS: CNS medication use is independently associated with an increased
      risk of future incident mobility limitation in community dwelling elderly.
      Further studies are needed to determine the impact of reducing CNS medication
      exposure on mobility problems.

PMID- 19585467
TI  - Bile acid-binding activity of young persimmon (Diospyros kaki) fruit and its
      hypolipidemic effect in mice.
AB  - The hypolipidemic effects and bile acid-binding properties of young persimmon
      (Diospyros kaki) fruit were examined. In an animal experiment, male C57BL/6.Cr
      mice (n = 5) were fed an AIN-76-modified high fat diet supplemented with 2% or 5%
      (w/w) dried young persimmon fruit (YP) for 10 weeks. The intake of YP
      significantly enhanced fecal bile acid excretion and lowered the concentration of
      hepatic lipids and plasma cholesterol. Analysis of gene expression in liver
      tissue showed that 2% or 5% YP up-regulated the expression of the sterol
      regulatory element-binding protein-2 gene. In the 5% group, there were increased
      expressions of the genes for cholesterol 7alpha-hydroxylase and the low-density
      lipoprotein receptor. Next, the bile acid-binding ability of YP was analysed in
      vitro using cholic acid (CA). In 100-2000 microM CA solutions, 1% (w/v) YP
      adsorbed approximately 60% of CA, while dried mature persimmon fruit adsorbed
      approximately 20% of CA. The positive control, cholestyramine, adsorbed
      approximately 80% of CA in the 100-2000 microM CA solutions. A crude tannin
      extract from YP, which contained 54.7% condensed tannins, adsorbed approximately
      78% of CA in the 2000 microM CA solutions. These results suggest that the ability
      of YP to bind bile acid contributes to its hypolipidemic effect in mice.

PMID- 19585468
TI  - Cytochrome P450 2C19 inhibitory activity of common berry constituents.
AB  - The cytochrome P450 enzyme CYP2C19 is involved in the metabolism of many commonly
      prescribed drugs, including proton pump inhibitors, antiepileptics and
      antidepressants. CYP2C19 inhibitors from food and food supplements may augment
      the toxicity of these agents and lead to noncompliance with treatment. The
      present investigation addresses CYP2C19 inhibition by 18 berry constituents using
      a chemiluminescent assay. Test compounds displayed inhibitory properties in a
      concentration-dependent fashion, with IC(50) values ranging from 20.2 microM up
      to >316 microM. In the order of decreasing effect size, anthocyanidins were
      followed by anthocyanidin-monoglycosides and procyanidins. Anthocyanidin
      diglucosides exhibited weak and biphasic effects. When compared with the CYP2C19
      inhibitor fluvoxamine, the flavonoids under study were 50- to 750-fold less
      potent. It is concluded that the above natural substances are moderate to poor
      inhibitors of CYP2C19 in vitro.

PMID- 19585469
TI  - Eviprostat suppresses urinary oxidative stress in a rabbit model of partial
      bladder outlet obstruction and in patients with benign prostatic hyperplasia.
AB  - Eviprostat is a phytotherapeutic agent that has been used widely for more than 40
      years in the treatment of benign prostatic hyperplasia (BPH) in Japan and
      Germany, and is known to have antioxidant activity. The present study
      investigated the effect of Eviprostat on the levels of the urinary oxidative
      stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in a rabbit model of surgical
      partial bladder outlet obstruction (PBOO) and in patients with lower urinary
      tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in
      urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of
      sham-operated rabbits. When twice-daily Eviprostat was administered orally
      throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was
      suppressed by 70%. In the clinical study, nine patients who received Eviprostat
      for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment.
      During Eviprostat treatment, the total International Prostate Symptom Score
      (IPSS) decreased from 16.56 +/- 2.74 to 13.67 +/- 2.30 and the quality of life
      score from 4.22 +/- 0.40 to 3.22 +/- 0.46. The findings provide evidence that the
      antioxidant activity of Eviprostat is responsible for its beneficial effects in
      the treatment of BPH.

PMID- 19585470
TI  - Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a
      dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human
      breast cancer cells.
AB  - Schizandrin is one of the main dibenzocyclooctadiene lignans present in the fruit
      of Schisandra chinensis (Schisandraceae). Biological activities including
      hepatoprotective, antiviral and neuroprotective effects of schizandrin and other
      dibenzocyclooctadiene lignans have been reported previously. However, the
      antiproliferative effect of schizandrin against human cancer cells has been
      poorly determined to date. This study examined the antiproliferative effect of
      schizandrin in human breast cancer cells. Schizandrin exhibited growth inhibitory
      activities in cultured human breast cancer cells, and the effect was the more
      profound in estrogen receptor (ER)-positive T47D cells than in ER-negative MDA-MB
      231 cells. When treated with the compound in T47D cells, schizandrin induced the
      accumulation of a cell population in the G0/G1 phase, which was further
      demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of
      the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A,
      CDK2 and CDK4. These results suggest that schizandrin inhibits cell proliferation
      through the induction of cell cycle arrest with modulating cell cycle-related
      proteins in human breast cancer cells.

PMID- 19585471
TI  - Hypericum perforatum L. (St John's wort) extract Ze 117 inhibits dopamine re
      uptake in rat striatal brain slices. An implication for use in smoking cessation
      treatment?
AB  - Classic synthetic antidepressant drugs, as well as St John's wort extract (SJW),
      directly inhibit the re-uptake of norepinephrine (NE) and/or serotonin (5-HT)
      into pre-synaptic axons. With chronic treatment they induce adaptive changes in a
      number of neurotransmitter receptors in synaptic membranes. The immediate effects
      of SJW Ze 117, an extract low in hyperforin content, on the specific dopamine
      (DA) uptake were studied in rat striatal brain slices and compared with the
      effects on NE and 5-HT uptake in rat cortical brain slices. Specific DA uptake
      was inhibited in a dose dependent manner. In contrast to the findings in
      synaptosomal preparations published so far, the extract showed different
      inhibitory potencies for the respective transporters. The potencies for the
      uptake inhibition of NA, DA and 5-HT were 30, 7 and 1, respectively. The results
      indicate that the SJW Ze 117 extract interferes in three ways with the individual
      uptakes of the relevant neurotransmitters that are considered to be causal in the
      development of depression. This observation, the concomitant and potent
      inhibition of DA re-uptake by SJW extract, may additionally provide a rationale
      for the treatment of nicotine or drug addiction with SJW.

PMID- 19585472
TI  - Efficacy of purslane in the treatment of oral lichen planus.
AB  - This study evaluated the effectiveness of antioxidant-rich purslane in the
      treatment of oral lichen planus (OLP). A total of 37 biopsy-proven symptomatic
      OLP patients were selected for this randomized double-blind placebo-controlled
      trial. All subjects were divided into two groups to receive purslane (n = 20) or
      placebo (n = 17) for 3 months. Assessments were made at baseline, after 2 weeks
      and each month for 6 months, based on the visual analog scale (VAS) and clinical
      improvement including lesion type and size. Approximately 83% of the purslane
      patients showed partial to complete clinical improvement but 17% had no response.
      In the placebo group 17% experienced partial improvement, 73% did not respond and
      10% showed worsening. According to VAS scores, a partial to complete response was
      observed in all purslane-treated patients, while 71%, 15% and 14% of the controls
      demonstrated partial response, no response and worsening of the symptoms,
      respectively. A significant decrease in VAS scores was seen at the end of the
      study period (p < 0.001). No serious side-effects occurred in either of the
      groups. According to our findings purslane is clinically effective in the
      treatment of OLP. Considering the lack of side-effects during the study period,
      it may be a favorable alternative treatment for OLP.

PMID- 19585473
TI  - Hypoglycemic effect of aqueous extract of seabuckthorn (Hippophae rhamnoides L.)
      seed residues in streptozotocin-induced diabetic rats.
AB  - An extract of seabuckthorn (Hippophae rhamnoides L.) seed residues has been shown
      to possess hypoglycemic and hypolipidemic properties in normal mice. The present
      study investigated the effects of an aqueous extract of seabuckthorn seed
      residues (ASSR) on serum glucose, lipid profiles and antioxidant parameters in
      streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into
      four groups: a normal control group; diabetic control group; diabetic groups
      supplemented with 5 mg/kg body weight glibenclamide (reference drug) and 400
      mg/kg body weight ASSR. Diabetes in rats was induced by intraperitoneal injection
      of streptozotocin (45 mg/kg body weight). Vehicle (distilled water),
      glibenclamide and ASSR were administered orally to normal and diabetic rats once
      a day lasting for 4 weeks. The data showed that administration of ASSR
      significantly lowered the serum glucose, triglyceride and nitric oxide levels in
      diabetic rats. Moreover, ASSR treatment also increased serum superoxide dismutase
      activity and glutathione level markedly. These results show that ASSR has
      hypoglycemic, hypotriglyceridemic and antioxidant effects in streptozotocin
      induced diabetic rats, suggesting that ASSR supplementation can be useful in
      preventing diabetic complications associated with hyperlipidemia and oxidative
      stress.

PMID- 19585474
TI  - Cytotoxic guaianolide from Anthemis segetalis (Asteraceae).
AB  - Two epimeric guaianolides were isolated from the aerial parts of Anthemis
      segetalis. These compounds have not been detected in any Anthemis species so far.
      One of them was tested for cytotoxicity against human cervical cancer (HeLa) and
      murine melanoma (B16) cell lines showing appreciable activity.

PMID- 19585475
TI  - Effect of sinomenine on the in vitro intestinal epithelial transport of selected
      compounds.
AB  - Herbal products can interfere with allopathic medicinal treatment through
      pharmacokinetic and pharmacodynamic interactions. Although pharmacokinetic
      interactions that alter drug absorption may cause variable and unsatisfactory
      drug bioavailability, a drug absorption enhancement effect of a herb may be used
      to ensure sufficient absorption of poorly absorbable drugs. The effect of the
      hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium
      acutum, on the transepithelial electrical resistance and transport of different
      compounds (including cimetidine, vitamin C, rutin, luteolin and insulin) across
      Caco-2 epithelial cell monolayers was investigated in this study. Sinomenine HCl
      induced a concentration dependent lowering effect on the transepithelial
      electrical resistance of Caco-2 cell monolayers, which was completely reversible.
      Sinomenine HCl significantly increased the transport of all the test compounds in
      the apical-to-basolateral direction compared with the control group and decreased
      the transport of cimetidine, a P-glycoprotein substrate, in the basolateral-to
      apical direction. From these results it can be concluded that sinomenine HCl
      increases drug absorption across the intestinal epithelium by means of one or
      more mechanisms including a transient opening of the tight junctions (as
      indicated by a reduction in transepithelial electrical resistance) to allow for
      paracellular transport and/or inhibition of active drug efflux transport (as
      indicated by inhibition of basolateral-to-apical transport of cimetidine).

PMID- 19585476
TI  - Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce
      caspase-3-dependent apoptosis in oral cavity cancer cells.
AB  - EGb 761, extracted from Ginkgo biloba leaves, has been proven to induce caspase-3
      dependent apoptosis in oral cavity cancer cells. Since EGb 761 is a composition
      of various components, it is important to identify which components are
      responsible for its anticancer effects to reduce the total dosage and to avoid
      toxicity. Therefore, the study aimed to determine the effective compounds of EGb
      761 that induce apoptosis in oral cavity cancer cells and to identify whether
      caspase-3 was involved in apoptosis of oral cancer cells by EGb 761 components.
      The results of cell proliferation assays on oral cavity cancer cells showed that
      kaempferol and quercetin significantly inhibited cellular proliferation at a
      concentration of 40 microM. Flow cytometry showed that the antiproliferative
      effects of each component were due to increased apoptosis. Kaempferol and
      quercetin induced apoptosis in various oral cancer cell lines (SCC-1483, SCC-25
      and SCC-QLL1) and showed cleavage of poly (ADP-ribose) polymerase (PARP). Caspase
      3 activity assay revealed that induction of apoptosis by kaempferol and quercetin
      was caspase-3-dependent. In conclusion, the results suggest that kaempferol and
      quercetin, two components of EGb 761, effectively induce caspase-3-dependent
      apoptosis of oral cavity cancer cells and can be considered as possible anti-oral
      cavity cancer agents.

PMID- 19585477
TI  - Genotoxicity and antigenotoxicity evaluation of non-photoactivated hypericin.
AB  - The potential genotoxicity and antigenotoxicity of non-photoactivated hypericin
      was investigated in five experimental models. Hypericin was non-mutagenic in the
      Ames assay, with and without metabolic activation. It did not exert a protective
      effect against mutagenicity induced by 9-aminoacridine. In a yeast (Saccharomyces
      cerevisiae) assay, hypericin did not increase the frequency of mitotic crossovers
      or total aberrants at the ade(2) locus, the number of convertants at the trp5
      locus, or the number of revertants at the ilv1 locus. In combined application
      with 4-nitroquinoline-1-oxide, it significantly enhanced the number of revertants
      at the ilv1 locus at the highest concentration used. Hypericin was not mutagenic
      in the alga Chlamydomonas reinhardtii. However, in combined application with
      methyl methane sulfonate, toxicity and mutagenicity were slightly reduced. In a
      chromosome aberration assay using three mammalian cell lines, hypericin did not
      alter the frequency of structural chromosome aberrations, and in the DPPH radical
      scavenging assay, it did not exert any antioxidant effects.

PMID- 19585478
TI  - Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian
      syndrome. A randomized controlled trial.
AB  - Hirsutism in polycystic ovarian syndrome (PCOS), consequent to elevated androgen
      levels leads to significant cosmetic and psychological problems. Recent research
      in Turkey has shown that spearmint tea has antiandrogenic properties in females
      with hirsutism. No research has yet been undertaken to assess whether a reduction
      in androgen levels brought about by spearmint tea, translates to a clinical
      improvement in the degree of hirsutism. This study was a two centre, 30 day
      randomized controlled trial. Forty two volunteers were randomized to take
      spearmint tea twice a day for a 1 month period and compared with a placebo herbal
      tea. At 0, 15 and 30 days of the study serum androgen hormone levels and
      gonadotrophins were checked, the degree of hirsutism was clinically rated using
      the Ferriman-Galwey score and a questionnaire (the modified DQLI = Dermatology
      Quality of Life Index) was used to assess improvements in the level of self
      reported hirsutism. Forty one of 42 patients completed the study. Free and total
      testosterone levels were significantly reduced over the 30 day period in the
      spearmint tea group (p < 0.05). LH and FSH also increased (p < 0.05). Patient's
      subjective assessments of their degree of hirsutism scored by the modified DQLI
      were significantly reduced in the spearmint tea group (p < 0.05). There was,
      however, no significant reduction in the objective Ferriman-Galwey ratings of
      hirsutism between the two trial groups over the trial duration (p = 0.12). There
      was a clear and significant alteration in the relevant hormone levels. This is
      associated clinically with a reduction in the self-reported degree of hirsutism
      but unfortunately not with the objectively rated score. It was demonstrated and
      confirmed that spearmint has antiandrogen properties, the simple fact that this
      does not clearly translate into clinical practice is due to the relationship
      between androgen hormones and follicular hair growth and cell turnover time.
      Simply put, the study duration was not long enough. The original studies from
      Turkey were in fact only 5 days long. The time taken for hirsutism to resolve is
      significant and a much longer future study is proposed as the preliminary
      findings are encouraging that spearmint has the potential for use as a helpful
      and natural treatment for hirsutism in PCOS.

PMID- 19585479
TI  - Studies on the effects of oral administration of nutrient mixture, quercetin and
      red onions on the bioavailability of epigallocatechin gallate from green tea
      extract.
AB  - Epigallocatechin gallate (EGCG), a main anticancer component in green tea, has a
      poor bioavailability in rats and humans due to oxidation, metabolism and its
      efflux. It was hypothesized that nutrients that address these problems might
      result in increased bioavailability. Plasma concentrations of EGCG at various
      time intervals were determined to calculate and compare the pharmacokinetic
      parameters after oral administration of green tea extract (GTE) or GTE as a
      nutrient mixture (E) or E + quercetin (Q)/red onions. In rat studies,
      supplementation of GTE with other nutrients (E) or E + Q raised the plasma C(max)
      from 55.29 +/- 1.70 to 61.94 +/- 1.70 ng/mL and 94.44 +/- 1.59 ng/mL,
      respectively. The corresponding t((1/2)) elimination was 2.04 +/- 0.2 h, 3.63 +/-
      0.66 h and 2.28 +/- 0.049 h. The AUC(0-24h) were 510.16 +/- 9.88 for GTE, 601.72
      +/- 19.10 ng.h/mL for E and 794.08 +/- 15.27 ng x h/mL (p < or = 0.05) for E + Q.
      In human studies when GTE was fed as GTE or E or E + red onions, the C(max)
      values were 348.4 +/- 76.6, 384.0 +/- 78.5 ng/mL and 468.4 +/- 131.4. AUC(0-8h)
      was 1784.1 +/- 56.06 (GTE), 1971.5 +/- 566.5 ng x h/mL (E) and 2490 +/- 878.1 (E
      + Q), but the change in t((1/2)) elimination was not significant.In conclusion,
      it is possible to increase the bioavailability of EGCG by supplementing it with
      nutrients and quercetin.

PMID- 19585480
TI  - Protective effect of Morinda citrifolia fruits on beta-amyloid (25-35) induced
      cognitive dysfunction in mice: an experimental and biochemical study.
AB  - The neuroprotective effect of an ethyl acetate extract of Morinda citrifolia
      (Rubiaceae) Linn. fruits (EMC, ethyl acetate extract of Morinda citrifolia) at
      doses of 200 and 400 mg/kg, p.o. was studied on beta-amyloid (25-35) peptide
      induced cognitive dysfunction in mice. In the step-down inhibitory avoidance, EMC
      exhibited a significant increase in short-term memory and long-term memory (p <
      0.05). A significant decrease (p < 0.01) in escape latency was noticed in the
      animals in the water maze. A significant increase (p < 0.01) in alteration of
      behavior was exhibited upon administration of EMC 200 and 400 mg/kg on the Y
      maze. Exploratory parameters such as line crossings, head dipping and rearing
      were increased significantly in EMC treated groups in a dose-dependent manner (p
      < 0.05 and p < 0.01). A significant reduction (p < 0.05) in acetyl cholinesterase
      activity was noticed in the EMC 200 and 400 mg/kg treated groups. The level of
      monoamine oxidase-A was decreased by the administration of EMC 200 and 400 mg/kg
      (p < 0.05 and p < 0.01, respectively). EMC at a dose of 400 mg/kg exhibited a
      significant increase (p < 0.01) in the levels of serotonin and dopamine.
      Antioxidant enzymes such as superoxide dismutase, glutathione reductase,
      glutathione peroxidase and ascorbic acid were decreased significantly in the b
      amyloid peptide injected group, whose levels were restored significantly (p <
      0.01) by the administration of EMC (400 mg/kg).

PMID- 19585482
TI  - The neuropsychopharmacological effects of Catha edulis in mice offspring born to
      mothers exposed during pregnancy and lactation.
AB  - Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and
      widespread habit in East Africa and the Middle East. Although a body of knowledge
      exists about the adverse effects of khat during pregnancy, data are sparse with
      regard to the consequences of long-term exposure during pregnancy and lactation.
      The present work, therefore, was initiated to evaluate the
      neuropsychopharmacological effects of Catha edulis exposure during pregnancy and
      lactation in mice at postnatal day 28. To this effect, a lyophilized extract of
      khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive
      control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water
      (negative control, CONT) were administered daily to pregnant mice from
      gestational day 6 until weaning. Neuropsychopharmacological measurements were
      done by making use of a battery of neurobehavioural and cognitive tests.
      Moreover, toxicity to liver and kidney was also evaluated by determining
      biochemical markers for possible tissue damage. K200 produced significant motor
      in-coordination and emotional instability; as revealed by impairment in both
      cliff avoidance (p < 0.01) and forelimb grip strength (p < 0.001), as well as by
      an increase in stereotyped behaviour such as grooming (p < 0.05), and in the
      percent of time spent in open arms (p < 0.05). On the other hand, K100 had an
      effect only on grip strength where a decrement was noted (p < 0.01). A different
      pattern emerged with AMP whilst it increased duration of sniffing (p < 0.05),
      neither grip strength nor the time spent in the open arm was affected compared
      with CONT. Increased latency to reach the goal box and the number of wrong
      decisions (p < 0.05) in both the learning and the recall tests was observed with
      K200 and AMP. By contrast, both doses of khat and AMP equally affected
      performance in the Y-maze (p < 0.05). Alterations in the biochemical indices of
      liver and kidney function were also noted with AMP and K200. These findings
      indicate that khat exposure produces dose-related central and peripheral effects
      during pregnancy and lactation which might pose a serious impediment to the
      physical and mental development of the offspring.

PMID- 19585481
TI  - Inhibitory effect of tea polyphenols on local tissue damage induced by snake
      venoms.
AB  - The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae)
      (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in
      Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae)
      venoms. These snake venom enzymes are responsible for the early effects of
      envenomation, such as local tissue damage and inflammation. The CS extract
      inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase
      in both venoms by in vitro neutralization and inhibited the hemorrhagic and the
      dermonecrotic activities of the venoms in vivo. It is suggested that the
      inhibitory potential of the CS extract against local tissue damage induced by
      snake venoms may be attributed to complexation and chelation between the venom
      proteins and the phenolic contents of the extract.

PMID- 19585483
TI  - Radiographic evidence of mandibular osteoporosis improvement in Wistar rats
      treated with Ginkgo biloba.
AB  - OBJECTIVE: Evaluate the effects of the extract of Ginkgo biloba (EGb) on the rat
      mandibular glucocorticoid-induced-osteoporosis. METHOD: 36 female rats were
      divided into six groups (n=6): control, osteoporosis, positive control and EGb1
      (14 mg/kg/day), EGb2 (28 mg/kg/day), and EGb3 (56 mg/kg/day) treatment.
      Treatments were conducted for 30 days after osteoporosis induction. The animals
      were euthanized and their left mandibles were removed and radiographed to
      evaluate the cortical and the periodontal bone support. The control group was
      compared with the osteoporosis group (Student's t-test). The other groups were
      analyzed by ANOVA test followed by Tukey post-hoc test (p < 0.05). RESULTS: There
      was a significant reduction in periodontal bone support in the osteoporosis
      group. The positive control group showed a significant increase in the mesial
      periodontal bone support, as well as the EGb group treated with 28 and 56 mg/Kg,
      which showed a significant increase in the mesial and distal periodontal bone
      support. The mandibular cortical was not affected by osteoporosis; however, the
      group treated with EGb using 56 mg/Kg showed a significant increase in the
      thickness of the mandibular cortical. CONCLUSIONS: The EGb recovered the
      periodontal bone support and increased the mandibular cortical thickness. The EGb
      may be effective in the treatment of osteoporosis.

PMID- 19585484
TI  - Screening for acetylcholinesterase inhibitory activity in plant extracts from
      Argentina.
AB  - Plants are a potential source of bioactive compounds and offer a promising
      strategy for the treatment of neurological disorders such as Alzheimer's disease.
      The inhibitory effect of 73 native and naturalized plants collected from the
      central region of Argentina on acetylcholinesterase (AChE) was tested using
      microplate and TLC assays after solvent fractionation of complete ethanol
      extracts obtained from the plants. Organic fractions obtained from extracts of
      Achyrocline tomentosa (Asteraceae), Eupatorium viscidum (Asteraceae), Ruprechtia
      apetala (Polygonaceae) Trichocline reptans (Asteraceae) and Zanthoxylum coco
      (Rutaceae) presented strong inhibition of AChE (higher than 80%) at 1 mg/mL, with
      R. apetala and T. reptans being the most potent, showing complete inhibition of
      the enzyme. Their IC(50) values were 0.0779 and 0.1118 mg/mL, respectively.
      Aqueous fractions did not show any inhibitory activity on the enzyme. These
      results suggest that the most effective extracts deserve further investigation
      with the aim of obtaining new molecules for the treatment of neurodegenerative
      disorders.

PMID- 19585485
TI  - Hesperidin suppresses adjuvant arthritis in rats by inhibiting synoviocyte
      activity.
AB  - The present study was designed to investigate the effect of hesperidin on rat
      adjuvant arthritis (AA) and to elucidate the involvement of synoviocytes in this
      process. Freund's complete adjuvant was used to induce AA in rats. Secondary paw
      swelling and the index of immune organs of AA rats were measured. Macrophage-like
      synoviocytes were separated by the method of collagenase and trypsin digestion.
      Synoviocyte proliferation was assayed by MTT assay. TNF-alpha, IL-1beta and IL-10
      production of synoviocytes were examined with ELISA. The levels of TNF-alpha, IL
      1beta, IL-10 mRNA were determined using RT-PCR. It was found that intragastric
      hesperidin administration (80, 160 mg/kg) significantly inhibited secondary paw
      swelling and restored the index of immune organs of AA rats. Furthermore,
      synoviocyte proliferation in AA rats was apparently suppressed after hesperidin
      treatment, which was accompanied by decreased transcription as well as production
      of TNF-alpha and IL-1beta from synoviocytes. Hesperidin also markedly increased
      IL-10 at both protein and transcription levels in AA rats. In aggregate, the
      above results demonstrate that hesperidin has a therapeutic effect on AA and the
      mechanisms are partly related to inhibiting synoviocyte activity and modulating
      inflammatory cytokine production of synoviocytes which play a crucial role in the
      pathogenesis of AA.

PMID- 19585486
TI  - Screening of Kit inhibitors: suppression of Kit signaling and melanogenesis by
      emodin.
AB  - In search of novel antipigmentation agents, a set of 3,840 compounds with natural
      like synthetic or natural origin were screened against Kit (stem cell factor
      receptor). Emodin from the seed of Cassia tora and baicalin from Scutellariae
      radix showed potent inhibitory effects (IC(50) = 4.9 and 9.0 microM,
      respectively) on the phosphorylation of Kit. Emodin also blocked other receptor
      tyrosine kinase activities, such as epithelial growth factor receptor (EGFR),
      vascular endothelial growth factor receptor 2 (VEGFR-2), fibroblast growth factor
      receptor 1 (FGFR-1), platelet-derived growth factor receptor b (PDGFR-b). In
      contrast to emodin, aloe-emodin did not inhibit Kit activity at all. Emodin also
      blocked the cellular kinase activities of Kit and its down-stream p44/42 mitogen
      activated protein kinase (MAPK) in MO7e cells and human primary melanocytes.
      Emodin strongly suppressed the melanin synthesis triggered by stem cell factor
      (SCF) treatment. Also, emodin showed almost no toxicity up to 10 microM on
      cultured melanocytes as reported previously by other researchers. The results
      indicate that emodin is a good candidate for the development of antipigmentation
      agents since it can radically block the differentiation and proliferation of
      pigment cells by reducing Kit signaling.

PMID- 19585487
TI  - Determination of the lactate threshold and maximal blood lactate steady state
      intensity in aged rats.
AB  - The reliability of the lactate threshold (LT) determined in aged rats and its
      validity to identify an exercise intensity corresponding to the maximal blood
      lactate steady state (MLSS) were analyzed. Eighteen male aged Wistar rats
      (approximately 365 days) were submitted to two incremental swimming tests until
      exhaustion, consisting of an initial load corresponding to 1% of body mass (BM)
      and increments of 1% BM at each 3-min with blood lactate ([lac]) measurements.
      The LT was determined by visual inspection (LT(V)) as well by applying a
      polynomial function on the [lac]/workload ratio (LT(P)) by considering the
      vertices of the curve. For the MLSS, twelve animals were submitted, on different
      days, to 3-4 exercise sessions of 30-min with workload corresponding to 4, 5 or
      6% BM. The MLSS was considered the highest exercise intensity at which the [lac]
      variation was not higher than 0.07 mM.min(-1) during the last 20-min. No
      differences were observed for the test-retest results (4.9 +/- 0.7 and 5.0 +/-
      0.8 %BM for LTv; and 6.0 +/- 0.6 and 5.8 +/- 0.6 %BM for LTp) that did not differ
      from the MLSS (5.4 +/- 0.5 %BM). The LT identified for aged rats in swimming,
      both by visual inspection and polynomial function, was reliable and did not
      differ from the MLSS.

PMID- 19585488
TI  - TpMRK regulates cell division of Tetrahymena in response to oxidative stress.
AB  - TpMRK was identified as a stress-responsive mitogen activated protein kinase
      (MAPK)-related kinase and has been shown to play a critical role in the stress
      signalling in Tetrahymena cells. Here, we found that the mRNA expression of TpMRK
      was correlated with cell division of Tetrahymena with decreased expression
      occurring in cells prior to entering synchronous cell division induced by heat
      treatment. Notably, cell division was delayed with a lower division index of 40%
      after exposure to hydrogen peroxide while 85% of cells underwent cell division
      synchronously at 75 min after heat treatment without the oxidative exposure.
      Furthermore, inactivation of TpMRK signalling by p38 MAPK inhibitor SB203580 or
      MEK inhibitor PD 98059 partially derepressed cell division induced by hydrogen
      peroxide. Our data suggest that oxidative stimuli might cause aberration of
      synchronous cell division of Tetrahymena through activating the TpMRK cascade.

PMID- 19585489
TI  - Blood lipid levels in relation to glucose status in seven populations of Asian
      origin without a prior history of diabetes: the DECODA study.
AB  - BACKGROUND: Dyslipidaemia commonly coexists with diabetes. We investigated the
      association of lipid profiles with glucose levels in populations of Asian origin
      without a prior history of diabetes. METHODS: Cross-sectional data of 10,374 men
      and 12,552 women aged 30-74 years from 14 cohorts, representing seven populations
      of Asian origin were jointly analysed. Multivariable adjusted linear regression
      analyses with standardized regression coefficients (beta) were performed to
      estimate relationships between lipids and plasma glucose. RESULTS: Within each
      glucose category, fasting plasma glucose (FPG) levels were correlated with
      increasing levels of triglycerides (TGs), total cholesterol (TC), TC to high
      density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p < 0.05 in
      most of the ethnic groups) and inversely associated with HDL-C (p < 0.05 in some,
      but not all, of the populations). The association of lipids with 2-h plasma
      glucose (2hPG) followed a similar pattern as that for the FPG, except that an
      inverse relationship between HDL-C and glucose was more commonly observed for
      2hPG than for FPG among different ethnic groups. CONCLUSIONS: Hyperglycaemia is
      associated with adverse lipid profiles in Asians without a prior history of
      diabetes. The 2hPG appears to be more closely associated with lipid profiles than
      does FPG. When assessing the risk of cardiovascular disease, the association of
      the dyslipidaemia with intermediate hyperglycaemia needs to be considered.

PMID- 19585491
TI  - A novel model of bone-metastatic prostate cancer in immunocompetent mice.
AB  - BACKGROUND: Bone metastasis is a frequent and catastrophic consequence of
      prostate cancer for which only palliative treatment is available. Animal models
      of bone metastatic prostate cancer are necessary for understanding disease
      mechanisms but few models exist. METHODS: We have used the murine prostate
      carcinoma cell line RM1 to generate a bone metastatic model of prostate cancer.
      Repeated intracardiac injection of RM1 cells followed by isolation of cells from
      bone tumors has yielded a cell line with strong bone-metastatic potential, RM1
      bone metastatic (BM). RESULTS: This cell line metastasizes to multiple bony sites
      in over 95% of injected C57BL/6 mice and is far less tropic to soft tissues. Bone
      tumors produced by the RM1(BM) cell line show no preference for particular
      skeletal sites as most bones are affected. Histology, and micro-computed
      tomography show that RM1(BM) cells form osteolytic tumors, but with evidence of
      osteoblastic changes. In vitro the RM1 cells express E-cadherin but not vimentin,
      do not form colonies in soft agar, are non-invasive but are more motile than the
      parent cell line. CONCLUSIONS: This model provides a novel means for identifying
      cellular and molecular mechanisms that contribute to bone metastasis and allow
      for preclinical testing of therapies to prevent and treat tumor metastasis to
      bone. Finally as the syngeneic tumor cells are injected into immunocompetent
      mice, this model will provide a means to study interactions between the immune
      system, tumors and bone, and therapies that target such interactions.

PMID- 19585492
TI  - Assessment of "grading" with Ki-67 and c-kit immunohistochemical expressions may
      be a helpful tool in management of patients with flat epithelial atypia (FEA) and
      columnar cell lesions (CCLs) on core breast biopsy.
AB  - It is essential to reach a better understanding of "flat epithelial
      atypia/columnar cell lesions" (FEA/CCLs) in breast core biopsies. Our aim was to
      explore their biological nature, in order to predict the likelihood of an upgrade
      to carcinoma. "Cytological grading" has been specially focused, in view of its
      possible utility in the choice of management. One hundred thirty of a total of
      900 cases core needle (CN)/vacuum-assisted biopsies (VABs), with diagnoses of
      "hyperplasia" and "atypia" were retrospectively re-evaluated. Pathological
      findings of further excision biopsies (FEBs) performed in 40/75 patients with
      follow-up were compared with the previous diagnoses. In all cases, both Ki-67 and
      c-kit immunoreactivities were explored and compared with both normal breast
      tissues and subsequently documented cancers, with special reference to the
      hyperplastic FEA/CCLs, with "mild" atypia (FEA/CCHAm). Sixteen cases were re
      diagnosed as "usual ductal hyperplasia" (UDH), 60 as "columnar cell hyperplasia"
      (CCH), and 54 as FEA/CCHA, 30 of which FEA/CCHAm and 24 FEA/CCHAh (with high
      atypia). Significantly, the Ki-67 index proved to be on the increase and c-kit
      expression on the decrease in FEA/CCHA lesions, mainly in the FEA/CCHAh group and
      in the subsequently observed cancers, compared with either benign tissues or the
      FEA/CCH cases. It was also significant that most of the carcinomas were found in
      FEBs within the FEA/CCHAh group. In this study cytological grading, together with
      Ki-67 and c-kit indices, proved to be helpful in FEA/CCLs evaluation. With regard
      to FEA/CCHAm lesions, an adequate surveillance appears to be a more appropriate
      management tool than FEB, as a result of their biological nature and behavior.

PMID- 19585490
TI  - Cell cycle regulator cdk2ap1 inhibits prostate cancer cell growth and modifies
      androgen-responsive pathway function.
AB  - BACKGROUND: We evaluated the effect of expressing the cell cycle regulator
      cdk2ap1, downregulated in prostate cancer cell lines, in inhibiting prostate
      cancer cell growth. METHODS: Expression of cdk2ap1 using a tet-inducible
      lentiviral system modified growth rate, induced cell cycle arrest and apoptosis
      and reduced the invasive ability of prostate cancer cell lines, as assayed by
      cell viability, cell cycle profiling, Caspase 3/7 detection, and matrigel
      invasion assays. We examined the effect of expressing cdk2ap1 on gene expression
      profiles of cytokine, invasion, apoptotic, and androgen response pathways using
      quantitative real-time PCR, and used androgen-responsive reporter gene assays,
      and methylation-sensitive PCR to examine the mechanism of cdk2ap1 interaction
      with androgen-responsive pathways. RESULTS: The expression of cdk2ap1 correlated
      with a reduction in cellular growth, irrespective of inhibition or stimulation of
      androgen receptor (AR) signaling pathways. Cell cycle arrest, increased
      apoptosis, and a reduction in invasiveness phenotypes were observed upon cdk2ap1
      expression. Enhanced demethylation at the AR promoter, AR expression increases,
      and enhanced AR transcriptional activity correlated with cdk2ap1 expression.
      CONCLUSIONS: Our findings support a novel concept by which cell cycle inhibitor
      genes can impact prostate cancer phenotypes by restoring a tumor suppressive
      function to androgen-responsive pathways and this function may involve modulation
      of a subset of functions of the AR.

PMID- 19585493
TI  - Body mass index and mortality from lung cancer in smokers and nonsmokers: a
      nationally representative prospective study of 220,000 men in China.
AB  - Low body mass index (BMI) has been associated with increased risk of lung cancer.
      However, the nature of the association, especially in populations with relatively
      low BMI, is less well characterized, as is the relevance to it of smoking. A
      nationally representative prospective cohort study included 217,180 Chinese men
      aged 40-79 years in 1990-91 who had no prior history of cancer and were followed
      up for 15 years. Standardized hazard ratios (HRs) were calculated for lung cancer
      mortality by baseline BMI. The mean baseline BMI was 21.7 kg/m(2), and 2,145 lung
      cancer deaths were recorded during 15 years of follow-up. The prevalence of
      smoking was strongly inversely associated with BMI, but no apparent relationship
      was seen between amount smoked (or other measures of smoking intensity) and BMI
      among smokers. Overall there was a strong inverse association between BMI and
      lung cancer mortality (p < 0.0001 for trend) after excluding the first 3 years of
      follow-up. This association appeared to be confined mainly to current smokers,
      with no apparent relationship in nonsmokers (p < 0.001 for difference between
      slopes). Among current smokers, the inverse association appeared to be log
      linear, with each 5 kg/m(2) lower BMI associated with a 35% (95% confidence
      interval: 24-46%; p < 0.0001) higher lung cancer mortality, and it persisted
      after excluding those who had reported poor health status or history of any
      disease or respiratory symptoms at baseline. In this relatively lean Chinese male
      population, low BMI was strongly associated with increased risk of lung cancer
      only among current smokers.

PMID- 19585494
TI  - Multiple human papillomavirus genotype infections in cervical cancer progression
      in the study to understand cervical cancer early endpoints and determinants.
AB  - Determining the causal attribution of human papillomavirus (HPV) genotypes to
      cervical disease is important to estimate the effect of HPV vaccination and to
      establish a type spectrum for HPV-based screening. We analyzed the prevalence of
      HPV infections and their attribution to cervical disease in a population of 1,670
      women referred to colposcopy for abnormal cytology at the University of Oklahoma.
      HPV genotyping was performed from cytology specimens using the Linear Array assay
      that detects 37 HPV genotypes. We used different methods of type attribution to
      revised cervical disease categories. We found very high prevalence of multiple
      HPV infections with up to 14 genotypes detected in single specimens. In all
      disease categories except for cancers, there was a significant trend of having
      more infections at a younger age. We did not see type interactions in multiple
      genotype infections. HPV16 was the most frequent genotype at all disease
      categories. Based on different attribution strategies, the attribution of vaccine
      genotypes (6, 11, 16, 18) ranged from 50.5 to 67.3% in cancers (n = 107), from
      25.6 to 74.8% in CIN3 (n = 305), from 15.2 to 52.2% in CIN2 (n = 427), and from
      6.6 to 26.0% in <CIN2 (n = 708). In the HSIL cytology group (n = 651),
      attribution ranged from 26.1 to 64.7%. The attribution of vaccine types to HSIL
      was substantially higher compared to the lower cytology categories. The potential
      range of HPV genotype attribution is wide at the disease categories <CIN2 to
      CIN3. Genotyping from cervical lesions and analyzing viral oncogene expression
      can improve estimates of HPV genotype attribution.

PMID- 19585495
TI  - Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical
      cancer in the Swedish population--a candidate gene approach.
AB  - High-risk human papillomavirus (hrHPV) infection is the major risk factor for
      cervical cancer (CxCa). The role of genetic susceptibility in the disease has
      been suggested, but the existing data lack consistency. We conducted a nested
      case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish
      population-based cohorts to examine the association of common genetic variants
      with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms
      in 14 genes were selected on the basis of reported association or mechanistic
      plausibility with an HPV infection or cervical cancer development. Genotyping was
      conducted using multiplex PCR and Luminex technology. A significant association
      of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds
      ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the
      LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14,
      95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally,
      the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an
      increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50,
      respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95%
      CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of
      the effect of smoking. We did not find any association of risk with polymorphisms
      in genes related to the innate immune system. In conclusion, our study provides
      evidence for genetic susceptibility to CxCa due to variations in genes involved
      in the immune system and in cell cycle.

PMID- 19585496
TI  - Prevalence and predictors of abandonment of therapy among children with cancer in
      El Salvador.
AB  - Abandonment of therapy is one of the most common causes of treatment failure
      among children with cancer in low-income countries. Our objectives were to
      describe the prevalence and predictors of abandonment among such children with
      cancer in El Salvador. We analyzed data on patients younger than 16 years,
      diagnosed with any malignancy between January 2001 and December 2003 at the
      Benjamin Bloom National Children's Hospital, San Salvador. Among 612 patients,
      353 were male (58%); the median age at diagnosis was 5.1 years; 59% of patients
      were diagnosed with leukemia/lymphoma, 28% with solid tumors and 13% with brain
      tumors. The prevalence of abandonment was 13%. Median time to abandonment was 2.0
      (range 0-36) months. In univariate analyses, paternal illiteracy [odds ratio (OR)
      3.8, 95% confidence interval (CI) 2.0-7.2; p = 0.001]; maternal illiteracy (OR =
      5.1, 95% CI 2.5-10; p < 0.0001); increasing number of household members (OR =
      1.2, 95% CI 1.1-1.3; p = 0.004); and low monthly household income (OR per $100 =
      0.59, 95% CI 0.45-0.75; p < 0.0001) all significantly increased the risk of
      abandonment, whereas travel time to hospital did not. In multiple regression
      analyses, low monthly income and increased number of people in the household were
      independently predictive of abandonment. In conclusion, in El Salvador, despite
      the provision of free treatment, socioeconomic variables significantly predict
      increased risk of abandonment of therapy. Understanding the pathways through
      which socioeconomic status affects abandonment may allow the design of effective
      interventions.

PMID- 19585498
TI  - Epidemiologic evaluation of pharmaceuticals with limited evidence of
      carcinogenicity.
AB  - Thorough review by the International Agency for Research on Cancer (IARC) has
      resulted in classifying many substances, including pharmaceuticals, as probably
      or possibly carcinogenic to humans, based on experiments on animals or limited
      data on humans. We evaluated 9 such pharmaceuticals for evidence of
      carcinogenicity in patients receiving them in a large medical care program with
      automated pharmacy records and a cancer registry. Nested case-control analyses
      were performed in a cohort of 6.5 million subscribers with up to 12 years of
      follow-up, focusing on cancer sites suggested by previous evidence and other
      sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose
      response. Unmeasured confounding was estimated in sensitivity analyses. We found
      some supportive evidence for carcinogenicity of griseofulvin, metronidazole and
      phenytoin and for the known carcinogen, cyclophosphamide, which was added for
      validation of our data and analyses. Findings for chloramphenicol, iron-dextran
      complex, phenoxybenzamine and phenobarbital were essentially non-contributory.
      Confounding by cigarette smoking and prior thyroid disease could account,
      respectively, for associations of oxazepam with lung cancer and propylthiouracil
      with thyroid cancer. Although not definitive, these findings should be considered
      in the evaluations of these pharmaceuticals.

PMID- 19585497
TI  - Coffee drinking and risk of endometrial cancer--a population-based cohort study.
AB  - Coffee drinking has been reported to have beneficial effects on insulin
      resistance, which has been directly associated with endometrial cancer. Although
      a relationship between coffee consumption and endometrial cancer risk is
      biologically plausible, this hypothesis has been previously explored in only 2
      prospective studies, with a small number of cases. We used data from the Swedish
      Mammography Cohort, a population-based prospective cohort study of 60,634 women.
      During 17.6 years of follow-up, 677 participants were diagnosed with incident
      endometrial cancer (adenocarcinoma). We examined the association between self
      reported coffee consumption (at baseline 1987-90 and in 1997) and endometrial
      cancer risk using Cox proportional hazards models. Each additional cup (200 g) of
      coffee per day was associated with a rate ratio (RR) of 0.90 [95% confidence
      interval (CI), 0.83-0.97]. In women drinking 4 or more cups of coffee a day, the
      RR for the risk reduction of endometrial cancer was 0.75 (95% CI, 0.58-0.97) when
      compared with those who drank 1 cup or less. The association seemed largely
      confined to overweight and obese women, who showed a respective risk reduction of
      12% (95% CI, 0-23%) and 20% (95% CI, 7-31%) for every cup of coffee, but was not
      observed among normal-weight women. There was a statistically significant
      interaction between coffee consumption and body mass index (p(interaction) <
      0.001). These data indicate that coffee consumption may be associated with
      decreased risk of endometrial cancer, especially among women with excessive body
      weight. If confirmed by other prospective studies, these results are of major
      public health significance.

PMID- 19585499
TI  - Detection of cell-free BIRC5 mRNA in effusions and its potential diagnostic value
      for differentiating malignant and benign effusions.
AB  - The detection of circulating nucleic acids has long been explored for the
      diagnosis of a variety of clinical conditions. The aim of this study was to
      detect the cell-free mRNA expression of BIRC5 in patients with effusions and
      assess its potential diagnostic value. Pleural fluids and ascites samples were
      collected prospectively from 112 patients. The cell-free RNA was extracted from
      effusions and the mRNA expression of BIRC5 was detected using real-time RT-PCR.
      The expression of carcinoembryonic antigen (CEA) and biochemical markers in
      effusions was also assayed. Effusions were classified as benign or malignant on
      the basis of their definitive pathologic or cytologic diagnoses. The expression
      of cell-free BIRC5 mRNA was statistically significantly higher in the malignant
      group than in the benign group. BIRC5 mRNA was also significantly different
      between patients with Stage III and Stage IV non-small cell lung cancers. The
      sensitivity and diagnostic accuracy of BIRC5 were 79.0 and 81.3%, whereas a
      combination of CEA and BIRC5 reached 86.4% sensitivity and 88.4% accuracy. These
      results indicate that effusions with higher levels of cell-free BIRC5 mRNA are
      more likely to be malignant. Determination of BIRC5 and CEA in effusions could
      enhance diagnostic value in the diagnosis of malignant effusions.

PMID- 19585500
TI  - Population dynamics of serologically identified coinfections with human
      papillomavirus types 11, 16, 18 and 31 in fertile-aged Finnish women.
AB  - Licensed human papillomavirus (HPV) vaccines are expected to prevent high-risk
      (hr) HPV-infections (most notably types 16 and 18). Whether HPV vaccination will
      change the distribution of hrHPVs at the population level is open, since
      competition between HPV types is not well understood. Two stratified random
      subcohorts (1983-1997 and 1995-2003) of 7,815 and 3,252 women with a minimum of 2
      pregnancies (<32 years) were selected from the Finnish Maternity Cohort. Using
      ELISA based on virus-like particles (VLP), we determined antibodies to HPV11, 16,
      18 and 31 in paired sera of the women and used Poisson regression models to
      estimate the risk of further infection with other HPV types in those positive for
      HPV16 or HPV18 at baseline. Baseline HPV16 seropositivity was associated with
      increased risk of later infections with HPV18 (3.1, 95% CI: 1.7, 5.6). HPV18
      seropositivity was associated with increased risk of HPV16 (3.9, 95% CI: 2.5,
      6.1). Our observations favor a coinfection rather than superinfection model for
      the different HPV types and are not suggestive for type-replacement following HPV
      vaccination.

PMID- 19585501
TI  - Dietary glucosinolate intake and risk of prostate cancer in the EPIC-Heidelberg
      cohort study.
AB  - Glucosinolates (GLS) are secondary plant metabolites occurring in cruciferous
      vegetables. Their biologically active break-down products show cancer preventive
      properties in animal and cell studies. So far, epidemiologic studies, using
      consumption of cruciferous vegetables as proxy for GLS intake, yielded
      inconsistent results. Here, we evaluated the association between dietary intake
      of GLS in comparison with consumption data of GLS-containing foods and the risk
      of prostate cancer. The study population comprised 11,405 male participants of
      the prospective EPIC-Heidelberg cohort study. During a mean follow-up time of 9.4
      years, 328 incident cases of prostate cancer occurred. At recruitment, habitual
      food consumption was assessed by a validated food frequency questionnaire, and
      intake of individual GLS was estimated by means of a newly compiled database on
      food content of GLS. Adjusted hazard ratios (HR) for prostate cancer were
      calculated using the Cox proportional hazard model. Median daily intake of total
      GLS was 7.9 mg/day (interquartile range 5.1-11.9 mg/day). The risk of prostate
      cancer decreased significantly over quartiles of total GLS intake (multivariate
      HR [4th vs. 1st quartile] 0.68, 95% CI 0.48-0.97, p(trend) 0.03). Associations
      with GLS-containing food intake were weaker. Among GLS subgroups, aliphatic GLS
      showed the strongest inverse association with cancer risk. Analyses stratified by
      tumor stage and grade gave hint to inverse associations for localized and low
      grade cancers. This study shows an inverse association between dietary intake of
      GLS and the risk of prostate cancer. Because this is the first prospective study
      using individual GLS intake data, confirmation in other studies is warranted.

PMID- 19585503
TI  - Characteristics of menstruation and pregnancy and the risk of lung cancer in
      women.
AB  - Lung tissue, both normal and cancerous, has been found to express estrogen
      receptors and patterns of expression have differed between men and women,
      suggesting a possible role for hormone-related factors in lung carcinogenesis in
      women. Few epidemiological studies have examined hormone-related variables and
      lung cancer risk and the findings have not been consistent. We investigated the
      association between characteristics of menstruation and pregnancy in relation to
      lung cancer risk in a population-based case-control study carried out in
      Montreal, Canada, including 422 women with lung cancer and 577 controls. For each
      variable, odds ratios (OR) and 95% confidence intervals (CI) were estimated using
      unconditional logistic regression modeling. Associations were also examined
      according to level of smoking and by lung cancer histology. All statistical tests
      were two-sided. Most characteristics of menstruation and pregnancy were not
      associated with lung cancer risk. However, an increased risk was observed for
      women who had had a non-natural menopause, which predominantly included women who
      had had a bilateral oophorectomy, compared with women who had had a natural
      menopause (OR = 1.92, 95% CI: 1.22-3.01). An inverse association with age at
      menopause was suggested. These results did not vary by level of smoking and they
      were similar for adenocarcinomas compared with other histological types. Our
      results suggest that hormonal factors, related to early menopause and/or ovary
      removal, may play a role in the risk of lung cancer. Further studies are needed
      to confirm these findings, and to assess the possible contribution of hormone
      replacement therapy.

PMID- 19585504
TI  - Attenuation of proteolysis-mediated cyclin E regulation by alternatively spliced
      Parkin in human colorectal cancers.
AB  - Parkin has a critical role in the ubiquitin-proteasome system as an E3-ligase
      targeting several substrates. Our recent finding that Parkin-deficient mice are
      susceptible to tumorigenesis provided evidence that Parkin is a tumor suppressor
      gene. Dysfunction of the Parkin gene is frequently observed in various human
      cancers, but the mechanism underlying the cell cycle disruption induced by Parkin
      dysfunction that leads to carcinogenesis is not known. Here, we demonstrated that
      Parkin expression in colonic epithelial cells is regulated in a cell cycle
      associated manner. Epidermal growth factor (EGF) stimulation upregulated Parkin
      gene expression in human colon cells. Inhibition of the phosphoinositide 3-kinase
      [PI(3)K]-Akt-dependent pathways suppressed growth factor-induced Parkin
      expression. The expression of alternatively spliced Parkin isoforms with various
      deletions spanning exons 3-6 was detected in 18 of 43 (42%) human colorectal
      cancer tissues. Wild-type Parkin induced the degradation of cyclin E protein, but
      the alternatively spliced Parkin identified in colon cancers showed defective
      proteolysis of cyclin E. These findings indicate that Parkin expression is
      induced by growth factor stimulation and is involved in the cell cycle regulation
      of colon cells. Tumor-specific expression of alternatively spliced Parkin
      isoforms might contribute to enhanced cell proliferation through the attenuation
      of proteolysis-mediated cyclin E regulation in human colorectal cancers.

PMID- 19585502
TI  - E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells
      treated with chlorophyllin.
AB  - Chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits
      cancer chemopreventive properties, but which also has been studied for its
      possible cancer therapeutic effects. We report here that human colon cancer cells
      treated with CHL accumulate in S-phase of the cell cycle, and this is associated
      with reduced expression levels of p53, p21, and other G(1)/S checkpoint controls.
      At the same time, E2F1 and E2F4 transcription factors become elevated and exhibit
      increased DNA binding activity. In CHL-treated colon cancer cells,
      bromodeoxyuridine pulse-chase experiments provided evidence for the inhibition of
      DNA synthesis. Ribonucleotide reductase (RR), a pivotal enzyme for DNA synthesis
      and repair, was reduced at the mRNA and protein level after CHL treatment, and
      the enzymatic activity was inhibited in a concentration-dependent manner both in
      vitro and in vivo. Immunoblotting revealed that expression levels of RR subunits
      R1, R2, and p53R2 were reduced by CHL treatment in HCT116 (p53(+/+)) and HCT116
      (p53(-/-)) cells, supporting a p53-independent mechanism. Prior studies have
      shown that reduced levels of RR small subunits can increase the sensitivity of
      colon cancer cells to clinically used DNA-damaging agents and RR inhibitors. We
      conclude that by inhibiting R1, R2, and p53R2, CHL has the potential to be
      effective in the clinical setting, when used alone or in combination with
      currently available cancer therapeutic agents.

PMID- 19585506
TI  - Melanocortin receptor 1 variants and melanoma risk: a study of 2 European
      populations.
AB  - Variation within the melanocortin receptor 1 (MC1R) gene, that influences
      phenotypic traits and susceptibility to melanoma, is abundant across the
      populations. We assessed and compared the risk of melanoma in 2 European
      populations, German and Spanish, by genotyping MC1R variants through direct DNA
      sequencing from 1,185 melanoma cases and 1,582 controls. The presence of any
      variant in both populations was associated with a significantly increased risk of
      melanoma (odds ratio OR = 1.67, 95% confidence interval CI 1.40-1.99). The
      population attributable fractions (PAF) associated with the MC1R variants in both
      populations was over 25%. However, the results showed a statistically significant
      (p < 0.0001) higher frequency of MC1R variants in the German (70%) than in the
      Spanish population (60%). The red-hair colour (RHC) variants, though associated
      with increased risk in both populations, were more common in the German than in
      the Spanish population (p < 0.0001). Interestingly, non-RHC variants increased
      the disease risk in the Spanish (OR = 1.60, 95% CI 1.20-2.14) but not in the
      German population (OR = 1.07, 95% CI 0.80-1.44). Although RHC variants explained
      a major proportion of the observed PAF in the German population, in the Spanish
      population the major contributor to the PAF was the non-RHC V60L variant. We also
      observed reduced historic linkage disequilibrium between the variants V92M and
      T314T in the gene in German melanoma cases. In conclusion, our data underscored
      the unambiguous importance of the MC1R variants towards the population burden of
      melanoma. However, the variants that are associated with the disease differ
      between the investigated populations.

PMID- 19585507
TI  - The potential impact of human papillomavirus vaccination in contemporary
      cytologically screened populations may be underestimated: an observational
      retrospective analysis of invasive cervical cancers.
AB  - The aim of this study was to determine the proportion of invasive cervical
      cancers attributable to human papillomavirus (HPV) types 16 and 18 in a
      contemporary, cytologically well-screened UK population. This was achieved in a
      retrospective observational analysis by HPV typing 453 archival invasive cervical
      cancers diagnosed between January 1, 2000 and September 1, 2006. Pathological
      material was collected from 9 hospitals across Wales (UK), and HPV typing and
      pathology review was conducted at a central laboratory. Genotyping for high-risk
      HPV DNA was performed by PCR-enzyme immunoassay using the GP5+/6+ primer set. DNA
      was successfully extracted from 297 cases. Two hundred and eighty cases were
      included in the final analysis. The proportion of cases which had only HPV 16
      and/or 18 was 219 of 280 (78.2%, 95% CI = 73.0-82.7); the proportion of cases
      which had HPV 16 or 18 and another HPV type was 230 of 280 (82.1%, 95% CI = 77.2
      86.2). The proportion of cervical cancers associated with infection with HPV
      types 16 and 18 has previously been estimated at around 70%. The appropriate
      figure for a cytologically well-screened UK population appears to be
      approximately 80%. Hence, the potential impact of the current vaccination
      programme may be underestimated.

PMID- 19585505
TI  - p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index
      squamous cell carcinoma of head and neck.
AB  - P73 plays an important role in modulating cell-cycle control, inducing apoptosis,
      and inhibiting cell growth. A novel noncoding p73 G4C14-to-A4T14 exon 2
      polymorphism was associated with risk of squamous cell carcinoma of the head and
      neck (SCCHN). We hypothesized that p73 G4C14-to-A4T14 polymorphism modulates risk
      of second primary malignancies (SPM) in patients after index SCCHN. We followed a
      cohort of 1,384 patients diagnosed with incident SCCHN between May 1995 and
      January 2007 for SPM development. Log-rank test and Cox proportional hazard
      models were used to compare SPM-free survival and SPM risk between the different
      genotype groups. Our results showed that patients carrying the p73 variant AT
      allele were less likely to develop SPM compared with the patients with p73 GC/GC
      genotype (Log-rank test, p = 0.013). Compared with the p73 GC/GC genotype, there
      was a significantly reduced risk of SPM associated with the p73 GC/AT genotype
      (HR, 0.61, 95% CI, 0.40-0.93) and the combined p73 GC/AT+AT/AT genotypes (HR,
      0.59, 95% CI, 0.39-0.89), but a nonsignificantly reduced risk for p73 AT/AT
      genotype (HR, 0.44, 95% CI, 0.14-1.41). The p73 AT allele was significantly
      associated with risk of SPM in an allele dose-response manner (p = 0.011 for
      trend). The risk of SPM associated with p73 variant genotypes (GC/AT+AT/AT) was
      more pronounced in several subgroups (e.g., older patients, men, minorities, ever
      smokers, and ever drinkers). Our results support that this p73 polymorphism may
      be a marker for risk of SPM among patients with an incident SCCHN.

PMID- 19585508
TI  - Breast cancer metastasis suppressor 1 coordinately regulates metastasis
      associated microRNA expression.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple
      tumor types without blocking tumorigenesis. BRMS1 forms complexes with SIN3,
      histone deacetylases and selected transcription factors that modify metastasis
      associated gene expression (e.g., EGFR, OPN, PI4P5K1A, PLAU). microRNA (miRNA)
      are a recently discovered class of regulatory, noncoding RNA, some of which are
      involved in neoplastic progression. Based on these data, we hypothesized that
      BRMS1 may also exert some of its antimetastatic effects by regulating miRNA
      expression. MicroRNA arrays were done comparing small RNAs that were purified
      from metastatic MDA-MB-231 and MDA-MB-435 and their nonmetastatic BRMS1
      transfected counterparts. miRNA expression changed by BRMS1 were validated using
      SYBR Green RT-PCR. BRMS1 decreased metastasis-promoting (miR-10b, -373 and -520c)
      miRNA, with corresponding reduction of their downstream targets (e.g., RhoC which
      is downstream of miR-10b). Concurrently, BRMS1 increased expression of metastasis
      suppressing miRNA (miR-146a, -146b and -335). Collectively, these data show that
      BRMS1 coordinately regulates expression of multiple metastasis-associated miRNA
      and suggests that recruitment of BRMS1-containing SIN3:HDAC complexes to, as yet
      undefined, miRNA promoters might be involved in the regulation of cancer
      metastasis.

PMID- 19585509
TI  - Novel HIV-1 clade B candidate vaccines designed for HLA-B*5101(+) patients
      protected mice against chimaeric ecotropic HIV-1 challenge.
AB  - Novel candidate HIV-1 vaccines have been constructed, which are tailor-designed
      for HLA-B*5101(+) patients infected with HIV-1 clade B. These vaccines employ
      novel immunogen HIVB-B*5101 derived from consensus HIV-1 clade B Gag p17 and p24
      regions coupled to two Pol-derived B*5101-restricted epitopes, which are together
      with a third B*5101 epitope in Gag dominant in HIV-1-infected long-term non
      progressing patients. Both plasmid DNA and modified vaccinia virus Ankara (MVA)
      vectors supported high expression levels of the HIVB-B*5101 immunogen in cultured
      cells. Heterologous DNA prime-recombinant MVA boost regimen induced efficiently
      HIV-1-specific CD8(+) T-cell responses in BALB/c mice. These vaccine-elicited T
      cells were multifunctional, killed efficiently target cells in vivo, and
      protected mice against challenge with ecotropic HIV-1/NL4-3 and ecotropic HIV
      1/NDK chimaeric viruses with HIV-1 clade B or D backbones, respectively, and
      ecotropic murine leukemia virus gp80 envelope, and therefore did so in the
      absence of anti-HIV-1 gp120 antibodies. These results support further development
      of HIVB-B*5101 vaccines in combined heterologous-modality regimens. The use of
      allele-specific vaccines in humans is discussed in the context of other
      developments in the HIV-1 field.

PMID- 19585510
TI  - Mycobacterium chelonae sensitisation induces CD4(+)-mediated cytotoxicity against
      BCG.
AB  - Significant variability in efficacy of live Mycobacterium bovis BCG as a
      tuberculosis vaccine is observed globally. Effects of pre-vaccination
      sensitisation to non-tuberculous environmental mycobacteria (Env) are suspected
      to underlie this phenomenon, but the mechanisms remain unclear. We postulated
      that it could be due to Env-specific T cells exerting cytotoxicity against BCG
      infected host cells. After murine sensitisation with heat-killed antigens of
      different Env species, splenocytes from M. chelonae (CHE)-sensitised mice exerted
      the strongest cytotoxicity against autologous BCG-infected macrophages. This
      cytotoxicity was correlated with reduced BCG viability. The cytotoxicity was
      reduced by the depletion of CD4(+), but not CD8(+) or CD56(+) cells, and CD4(+)
      cells showed higher percentage of cytotoxicity than CD4(-) cells, supporting a
      role for CD4(+) cells in CHE-induced, BCG-specific cytotoxicity. Additionally,
      this cytotoxicity was IFN-gamma, perforin and FasL dependent. After CHE
      sensitisation and subsequent BCG intranasal infection, there was significant
      expansion of lung CD4(+) cells, the main cell type producing IFN-gamma. This was
      associated with 2- and 6-fold reductions in lung BCG counts 1 and 3 wk,
      respectively post- infection, relative to non-sensitised mice. This is the first
      report describing cytotoxicity against BCG-infected cells as a mechanism
      underlying the influence of Env sensitisation on subsequent BCG responses.

PMID- 19585511
TI  - CREB and AP-1 activation regulates MKP-1 induction by LPS or M-CSF and their
      kinetics correlate with macrophage activation versus proliferation.
AB  - MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in
      innate immunity. This phosphatase inactivates ERK1/2, which are involved in two
      opposite functional activities of the macrophage, namely proliferation and
      activation. Here we found that although macrophage proliferation and activation
      induce MKP-1 with different kinetics, gene expression is mediated by the proximal
      promoter sequences localized between -380 and -180 bp. Mutagenesis experiments of
      the proximal element determined that CRE/AP-1 is required for LPS- or M-CSF
      induced activation of the MKP-1 gene. Moreover, the results from gel shift
      analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to
      the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with
      the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal
      transduction pathways that activate the induction of MKP-1 correlate kinetically
      with induction by M-CSF and LPS.

PMID- 19585512
TI  - The interaction between DC and Plasmodium berghei/chabaudi-infected erythrocytes
      in mice involves direct cell-to-cell contact, internalization and TLR.
AB  - Early interactions between blood-stage Plasmodium parasites and cells of the
      innate immune system are very important in shaping the adaptive immune response
      to malaria, and a number of studies have suggested that DC are responsible for
      this phenomenon. Therefore, we examined the capacity of murine BM-derived DC to
      internalize parasites, be activated and produce cytokines upon in vitro
      interaction with murine erythrocytes infected with two different strains of
      rodent malaria parasites (Plasmodium berghei and Plasmodium chabaudi chabaudi).
      We show that the increased expression of MHC class II and co-stimulatory
      molecules and increased production of cytokines by DC following Plasmodium
      infection involves internalization of infected RBC. Such DC activation not only
      requires direct cell-to-cell contact and internalization of infected RBC by DC
      but also involves TLR4, TLR9, MyD88 and signaling via NF-kappaB; however, TLR
      involvement in survival to Plasmodium infection was found to be negligible.

PMID- 19585513
TI  - Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in
      patients with cancer and obesity.
AB  - Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond
      rapidly by killing tumor cells and release cytokines that activate and regulate
      adaptive immune responses. They are essential for tumor rejection in various
      mouse models, but clinical trials in humans involving iNKT cells have been less
      successful, partly due to their rarity in humans compared with mice. Here we
      describe an accumulation of functional iNKT cells in human omentum, a migratory
      organ with healing properties. Analysis of 39 omental samples revealed that T
      cells are the predominant lymphoid cell type and of these, 10% expressed the
      invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any
      other human organ tested to date. About 15% of omental hematopoietic cells
      expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells
      killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental
      iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and
      with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These
      data suggest a novel role for the omentum in immune regulation and tumor immunity
      and identify it as a potential source of iNKT cells for therapeutic use.

PMID- 19585514
TI  - Mechanisms determining cell membrane expression of different gammadelta TCR chain
      pairings.
AB  - We investigated the ability of the most common TCR-gamma and delta chains to
      express on the cell surface. Vgamma1Cgamma4 and Vgamma7Cgamma1 chains paired with
      all TCR-delta chains tested, whereas Vgamma4Cgamma1 chains were found with
      Vdelta4 and Vdelta5, but not with Vdelta2 or Vdelta6 chains, and Vgamma2Cgamma2
      chains were expressed only with Vdelta5. Mapping studies showed that up to four
      polymorphic residues influence the different co-expressions of Vgamma1 and
      Vgamma2 chains with Vdelta chains. Unexpectedly, these residues are not located
      in the canonical gamma/delta interface, but in the outer part of the gammadelta
      TCR complex exposed to the solvent. Expression of functional Vdelta4 or Vdelta6
      chains in Vgamma2/Vdelta5(+) cells or of functional Vgamma2Cgamma2 in Vgamma1(+)
      cells reduced cell-surface expression of the gammadelta TCR. Taken together,
      these data show that (i) the Vgamma/Vdelta repertoire of mouse gammadelta T cells
      is reduced by physical constraints in their associations. (ii) Lack of
      Vgamma2/Vdelta expression is due to the formation of aberrant TCR complexes,
      rather than to an intrinsic inability of the chains to pair and (iii) despite not
      being expressed at the cell surface, the presence of a functionally rearranged
      Vgamma2 chain in gammadelta T cells results in reduced TCR levels.

PMID- 19585516
TI  - The effect of allogeneic in vitro stimulation and in vivo immunization on memory
      CD4(+) T-cell APOBEC3G expression and HIV-1 infectivity.
AB  - Allogeneic immunity is one of the most potent natural immune responses. APOBEC3G
      (A3G) is an intracellular anti-viral factor that deaminates cytidine to uridine.
      Allogeneic stimulation of human CD4(+) T cells in vitro upregulated A3G mRNA and
      a significant correlation was found between the mixed leukocyte reaction and A3G
      mRNA. The mechanism of upregulation of A3G mRNA involves interaction between HLA
      on DC and TCR of CD4(+) T cells, which is ZAP70 and downstream ERK phosphokinase
      signalling dependent and induces CD40L and A3G mRNA expression in CD4(+) T cells.
      Alloimmune-induced A3G was found to be significantly increased in CD45RA(-),
      CCR5(+) and CD45RA(-)CCR7(-) subsets of effector memory T cells. In vivo studies
      of women alloimmunized with their partners' PBMC also showed a significant
      increase in A3G protein in CD4(+) T cells, CD45RO(+) memory and CCR7(-) effector
      memory T cells. The functional effect of allostimulation upregulating A3G mRNA
      was demonstrated by a significant decrease in in vitro infectivity, using GFP
      labelled pseudovirus and confirmed by a decrease in HIV-1 (BaL) infection of
      primary CD4(+) T cells. The results suggest that alloimmunization offers an
      alternative or complementary strategy in inducing an innate anti-viral factor
      that inhibits HIV-1 infection.

PMID- 19585517
TI  - The C-type lectin DC-SIGN internalizes soluble antigens and HIV-1 virions via a
      clathrin-dependent mechanism.
AB  - Dendritic cells (DC), professional Ag-presenting cells located in mucosae and
      lymphoid organs, operate at the interface of innate and adaptive immunity and are
      likely the first cells to encounter invading HIV-1. Although the C-type lectin DC
      Specific ICAM-3-grabbing non-integrin (DC-SIGN) binds to several viruses,
      including HIV-1, its direct involvement in viral entry remains controversial.
      Despite its central role in DC function, little is known about the underlying
      molecular mechanism(s) of DC-SIGN-mediated Ag uptake. Here, we analyzed the early
      stages of DC-SIGN-mediated endocytosis and demonstrate that both membrane
      cholesterol and dynamin are required. Confocal microscopy and clathrin RNAi
      showed that DC-SIGN-mediated internalization occurs via clathrin-coated pits.
      Electron microscopy of ultrathin sections showed the involvement of DC-SIGN in
      clathrin-dependent HIV-1 internalization by DC. Currently, DC-specific C-type
      lectins are considered potential target in anti-tumor clinical trials. Detailed
      information about how different Ag are internalized via these receptors will
      facilitate the rational design of targeted therapeutic strategies.

PMID- 19585518
TI  - New luminol chemiluminescence reaction using diperiodatoargentate as oxidate for
      the determination of amikacin sulfate.
AB  - A new chemiluminescence (CL) reaction between luminol and diperiodatoargentate
      [K(2) [Ag (H(2)IO(6)) (OH)(2)]] was observed in alkaline medium. The CL intensity
      could be greatly enhanced by amikacin sulfate. Therefore a new CL method for the
      determination of amikacin sulfate was built by combining with flow injection
      technology. A possible mechanism of the CL reaction was proposed via the
      investigation of the CL kinetic characteristics, the CL spectrum and the UV
      absorption spectra of some related substance. The concentration range of linear
      response was 5.1 x 10(-8) to 5.1 x 10(-6)mol L(-1) with a detection limit of 1.9
      x 10(-8) mol L(-1) (3sigma). The proposed method had good reproducibility with a
      relative standard deviation of 2.8% (n = 7) for 5.1 x 10(-7) mol L(-1) of
      amikacin sulfate. It was successfully applied to determine amikacin sulfate in
      serum.

PMID- 19585519
TI  - The epigenetic regulators Bmi1 and Ring1B are differentially regulated in
      pancreatitis and pancreatic ductal adenocarcinoma.
AB  - Chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are associated
      with major changes in cell differentiation. These changes may be at the basis of
      the increased risk for PDAC among patients with chronic pancreatitis. Polycomb
      proteins are epigenetic silencers expressed in adult stem cells; up-regulation of
      Polycomb proteins has been reported to occur in a variety of solid tumours such
      as colon and breast cancer. We hypothesized that Polycomb might play a role in
      preneoplastic states in the pancreas and in tumour development/progression. To
      test these ideas, we determined the expression of PRC1 complex proteins (Bmi1 and
      Ring1b) during pancreatic development and in pancreatic tissue from mouse models
      of disease: acute and chronic pancreatic injury, duct ligation, and in K
      Ras(G12V) conditional knock-in and caerulein-treated K-Ras(G12V) mice. The study
      was extended to human pancreatic tissue samples. To obtain mechanistic insights,
      Bmi1 expression in cells undergoing in vitro exocrine cell metaplasia and the
      effects of Bmi1 depletion in an acinar cancer cell line were studied. We found
      that Bmi1 and Ring1B are expressed in pancreatic exocrine precursor cells during
      early development and in ductal and islet cells-but not acinar cells-in the adult
      pancreas. Bmi1 expression was induced in acinar cells during acute injury, in
      acinar-ductal metaplastic lesions, as well as in pancreatic intraepithelial
      neoplasia (PanIN) and PDAC. In contrast, Ring1B expression was only significantly
      and persistently up-regulated in high-grade PanINs and in PDAC. Bmi1 knockdown in
      cultured acinar tumour cells led to changes in the expression of various
      digestive enzymes. Our results suggest that Bmi1 and Ring1B are modulated in
      pancreatic diseases and could contribute differently to tumour development.

PMID- 19585521
TI  - Dys-regulated activation of a Src tyroine kinase Hck at the Golgi disturbs N
      glycosylation of a cytokine receptor Fms.
AB  - HIV-1 Nef accelerates the progression to AIDS by binding with and activating a
      Src kinase Hck, but underlying molecular basis is not understood. We revealed
      that Nef disturbed N-glycosylation/trafficking of a cytokine receptor Fms in an
      Hck-dependent manner, a possible trigger to worsen uncontrolled immune system.
      Here, we provide direct evidence that dys-regulated activation of Hck pre
      localized to the Golgi apparatus causes this Fms maturation arrest. A striking
      change in Hck induced by Nef other than activation was its skewed localization to
      the Golgi due to predominant Golgi-localization of Nef. Studies with different
      Nef alleles and their mutants showed a clear correlation among higher Nef-Hck
      affinity, stronger Hck activation, severe Golgi-localization of Hck and severe
      Fms maturation arrest. Studies with a newly discovered Nef-Hck binding blocker 2c
      more clearly showed that skewed Golgi-localization of active Hck was indeed the
      cause of Fms maturation arrest. 2c blocked Nef-induced skewed Golgi-localization
      of an active form of Hck (Hck-P2A) and Fms maturation arrest by Nef/Hck-P2A, but
      showed no inhibition on Hck-P2A kinase activity. Our finding establishes an
      intriguing link between the pathogenesis of Nef and a newly emerging concept that
      the Golgi-localized Src kinases regulate the Golgi function.

PMID- 19585522
TI  - Functional role of aquaglyceroporin 7 expression in the pancreatic beta-cell line
      BRIN-BD11.
AB  - Both mouse and rat pancreatic islet beta-cells were recently found to express
      aquaglyceroporin 7 (AQP7). In the present study, the expression and role of AQP7
      in the function of BRIN-BD11 cells were investigated. AQP7 mRNA and protein were
      detected by RT-PCR and Western blot analysis, respectively. In an isoosmolar
      medium, the net uptake of [2-(3)H]glycerol displayed an exponential time course
      reaching an equilibrium plateau value close to its extracellular concentration.
      Within 2 min of incubation in a hypotonic medium (caused by a 50 mM decrease in
      NaCl concentration), the [2-(3)H]glycerol uptake averaged 143.2 +/- 3.8% (n = 24;
      P < 0.001) of its control value in isotonic medium, declining thereafter
      consistently with previously demonstrated volume regulatory decrease. When
      isoosmolarity was restored by the addition of 100 mM urea to the hypotonic
      medium, [2-(3)H]glycerol uptake remained higher (112.1 +/- 2.8%, n = 24; P <
      0.001) than its matched control under isotonic conditions, indicating rapid entry
      of urea and water. Insulin release by BRIN-BD11 cells was 3 times higher in
      hypotonic than in isotonic medium. When glycerol (100 mM) or urea (100 mM) were
      incorporated in the hypotonic medium, the insulin release remained significantly
      higher than that found in the control isotonic medium, averaging respectively
      120.2 +/- 4.2 and 107.0 +/- 3.8% of the paired value recorded in the hypotonic
      medium. These findings document the rapid entry of glycerol and urea in BRIN-BD11
      cells, likely mediated by AQP7.

PMID- 19585523
TI  - Plant cell calcium-rich environment enhances thermostability of recombinantly
      produced alpha-amylase from the hyperthermophilic bacterium Thermotoga maritime.
AB  - In the industrial processing of starch for sugar syrup and ethanol production, a
      liquefaction step is involved where starch is initially solubilized at high
      temperature and partially hydrolyzed with a thermostable and thermoactive alpha
      amylase. Most amylases require calcium as a cofactor for their activity and
      stability, therefore calcium, along with the thermostable enzyme, are typically
      added to the starch mixture during enzymatic liquefaction, thereby increasing
      process costs. An attractive alternative would be to produce the enzyme directly
      in the tissue to be treated. In a proof of concept study, tobacco cell cultures
      were used as model system to test in planta production of a hyperthermophilic
      alpha-amylase from Thermotoga maritima. While comparable biochemical properties
      to recombinant production in Escherichia coli were observed, thermostability of
      the plant-produced alpha-amylase benefited significantly from high intrinsic
      calcium levels in the tobacco cells. The plant-made enzyme retained 85% of its
      initial activity after 3 h incubation at 100 degrees C, whereas the E. coli
      produced enzyme was completely inactivated after 30 min under the same
      conditions. The addition of Ca(2+) or plant cell extracts from tobacco and
      sweetpotato to the E. coli-produced enzyme resulted in a similar stabilization,
      demonstrating the importance of a calcium-rich environment for thermostability,
      as well as the advantage of producing this enzyme directly in plant cells where
      calcium is readily available.

PMID- 19585524
TI  - W7FW14F apomyoglobin amyloid aggregates-mediated apoptosis is due to oxidative
      stress and AKT inactivation caused by Ras and Rac.
AB  - We have previously reported that addition of prefibrillar aggregates (PFAs)
      derived from W7FW14F apomyoglobin mutant to NIH-3T3 cells affects their
      viability. In this article, we have found that cytotoxicity induced by PFAs in
      NIH 3T3 and SH-SY5Y human neuroblastoma cells was due to early activation of
      apoptotic cell death dependent from a caspase-3- and -9-mediated mitochondrial
      pathway. A time-dependent increase of intracellular ROS and an about twofold
      decrease of mitochondrial localization of scavenger protein MnSOD was found. The
      use of the anti-oxidant agent N-acetyl-cysteine (NAC) antagonized both the
      increase of intracellular ROS and apoptosis induced by PFAs. PFAs caused an about
      60% increase of the activity of both Ras and Erk-1/2 at 30 and 45 min while they
      were restored to basal levels at later time points. This effect was paralleled by
      a time-dependent decrease of the activity of the survival enzyme Akt. Effects
      similar to those on Ras activity were also recorded on the activity of the stress
      involved small GTP binding protein Rac that was about 75% increased after 30 min
      but resumed to basal levels at later time points. This effect was paralleled by a
      time-dependent activation of p38 kinase activity and HSP-70 expression. The use
      of both the ras farnesyltransferase inhibitor tipifarnib and the Rac geranyl
      geranyltransferase GGTI-298, but not of the MEK-1 inhibitor U0126 partially
      antagonized the effects of PFAs on apoptosis occurrence. On the other hand, the
      PI3K/Akt inhibitor LY 294002 potentiated apoptosis induced by PFAs. Our results
      indicate a role for Ras and Rac in the induction of both intracellular ROS
      increased levels and apoptosis mediated by PFAs and disclose a new scenario of
      intervention in neurodegenerative diseases.

PMID- 19585525
TI  - Impedance spectroscopy as a tool for non-intrusive detection of extracellular
      mediators in microbial fuel cells.
AB  - Endogenously produced, diffusible redox mediators can act as electron shuttles
      for bacterial respiration. Accordingly, the mediators also serve a critical role
      in microbial fuel cells (MFCs), as they assist extracellular electron transfer
      from the bacteria to the anode serving as the intermediate electron sink.
      Electrochemical impedance spectroscopy (EIS) may be a valuable tool for
      evaluating the role of mediators in an operating MFC. EIS offers distinct
      advantages over some conventional analytical methods for the investigation of MFC
      systems because EIS can elucidate the electrochemical properties of various
      charge transfer processes in the bio-energetic pathway. Preliminary
      investigations of Shewanella oneidensis DSP10-based MFCs revealved that even low
      quantities of extracellular mediators significantly influence the impedance
      behavior of MFCs. EIS results also suggested that for the model MFC studied,
      electron transfer from the mediator to the anode may be up to 15 times faster
      than the electron transfer from bacteria to the mediator. When a simple carbonate
      membrane separated the anode and cathode chambers, the extracellular mediators
      were also detected at the cathode, indicating diffusion from the anode under open
      circuit conditions. The findings demonstrated that EIS can be used as a tool to
      indicate presence of extracellular redox mediators produced by microorganisms and
      their participation in extracellular electron shuttling.

PMID- 19585526
TI  - Dynamic changes in chromatin structure through post-translational modifications
      of histone H3 during replication origin activation.
AB  - Genome duplication relies on the timely activation of multiple replication
      origins throughout the genome during S phase. Each origin is marked by the
      assembly of a multiprotein pre-replication complex (pre-RC) and the recruitment
      of the replicative machinery, which can gain access to replication origins on the
      DNA through the barrier of specific chromatin structures. Inheritance of the
      genetic information is further accompanied by maintenance and inheritance of the
      epigenetic marks, which are accomplished by the activity of histone and DNA
      modifying enzymes traveling with the replisome. Here, we studied the changes in
      the chromatin structure at the loci of three replication origins, the early
      activated human lamin B2 (LB2) and monkey Ors8 (mOrs8) origins and the late
      activated human homologue of the latter (hOrs8), during their activation, by
      measuring the abundance of post-translationally modified histone H3. The data
      show that dynamic changes in the levels of acetylated, methylated and
      phosphorylated histone H3 occur during the initiation of DNA replication at these
      three origin loci, which differ between early- and late-firing origins as well as
      between human- and monkey-derived cell lines. These results suggest that specific
      histone modifications are associated with origin firing, temporal activation and
      replication fork progression and underscore the importance of species
      specificity.

PMID- 19585528
TI  - Hybrid silica polymeric monolith-based in-tube microextraction and CE for
      determination of bisphenol A in beverages.
AB  - On-line concentration techniques in capillary electrophoresis, including stacking
      and sweeping, have a weak tolerance towards complex real samples. A phenyl
      functionalized hybrid silica monolithic polymeric capillary column (id 530
      microm) was prepared by in-situ co-condensation of phenyltriethoxysilane (PTES)
      and tetraethoxysilane (TEOS). In order to enhance the stability of a monolithic
      column within a wide-bore capillary, a novel and simple frit-preparation method
      for wide-bore capillaries was first introduced by immobilizing a short length of
      capillary of suitable outer diameter at the end of the monolithic capillary
      column during condensation of the sol-gel solution. The monolithic column was
      used for the extraction of bisphenol A (BPA) from cola samples, and the
      interfering compounds can be removed from the samples with 40% ACN solution (v/v)
      as eluent. The pretreated samples were further concentrated and separated using
      large-volume stacking and sweeping micellar electrokinetic chromatography. The
      method was successfully applied to the determination of bisphenol A spiked in
      cola, yielding a detection limit of 1.8 ng/mL. Close correlation coefficients and
      acceptable method reproducibility were obtained for bisphenol A over a linear
      range of 0.005-0.200 microg/mL.

PMID- 19585527
TI  - Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on
      human cytomegalovirus gene expression in vitro.
AB  - The nucleolus is a nuclear domain involved in the biogenesis of ribosomes, as
      well as in many other important cellular regulatory activities, such as cell
      cycle control and mRNA processing. Many viruses, including herpesviruses, are
      known to exploit the nucleolar compartment during their replication cycle. In a
      previous study, we demonstrated the preferential targeting and accumulation of
      the human cytomegalovirus (HCMV) UL83 phosphoprotein (pp65) to the nucleolar
      compartment and, in particular, to the nucleolar matrix of lytically infected
      fibroblasts; such targeting was already evident at very early times after
      infection. Here we have investigated the possible effects of rRNA synthesis
      inhibition upon the development of HCMV lytic infection, by using either
      actinomycin D or cisplatin at low concentrations, that are known to selectively
      inhibit RNA polymerase I activity, whilst leaving RNA polymerase II function
      unaffected. Following the inhibition of rRNA synthesis by either of the agents
      used, we observed a significant redistribution of nucleolar proteins within the
      nucleoplasm and a simultaneous depletion of viral pp65 from the nucleolus; this
      effect was highly evident in both unextracted cells and in nuclear matrices in
      situ. Of particular interest, even a brief suppression of rRNA synthesis resulted
      in a very strong inhibition of the progression of HCMV infection, as was
      concluded from the absence of accumulation of HCMV major immediate-early proteins
      within the nucleus of infected cells. These data suggest that a functional
      relationship might exist between rRNA synthesis, pp65 localization to the
      nucleolar matrix and the normal development of HCMV lytic infection.

PMID- 19585529
TI  - Preparation and characterization of polymethacrylate monolithic capillary columns
      with dual hydrophilic interaction reversed-phase retention mechanism for polar
      compounds.
AB  - Monolithic columns for capillary hydrophilic interaction liquid chromatography
      (HILIC) were prepared in fused-silica capillaries by radical co-polymerization of
      [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide and ethylene
      dimethacrylate in various binary and ternary porogen solvent mixtures with
      azobisisobutyronitrile as the initiator of the polymerization reaction. Columns
      showed mixed separation modes: reversed-phase (RP) in water-rich mobile phases
      and HILIC at high concentrations of acetonitrile (>60-80%) in aqueous-organic
      mobile phases. A continuous change in retention was observed at increasing
      concentration of water in acetonitrile, giving rise to characteristic U-turn
      plots of retention factors versus the concentration of water in the mobile phase,
      with minima corresponding to the transition between the mechanisms controlling
      the retention. The selectivity of organic polymer monolithic columns for HILIC
      separations can be varied by adjusting the concentration of sulfobetaine monomer
      and the composition of the porogen solvent in the polymerization mixture. Under
      HILIC conditions, the monolithic capillary sulfobetaine columns show separation
      selectivities for polar phenolic acids similar to those of a commercial silica
      based sulfobetaine ZIC-HILIC column, which, however, has limited selectivity in
      the RP mode due to lower retention.

PMID- 19585530
TI  - Extraction of genomic DNA using a new amino silica monolithic column.
AB  - A new amino silica monolithic column was developed for DNA extraction in a
      miniaturized format. The monolithic column was prepared in situ by polymerization
      of tetraethoxysilane (TEOS) and N-(beta-aminoethyl)-gamma
      aminopropylmethyldimethoxysilane (AEAPMDMS). DNA was loaded in 50 mM
      tris(hydroxylmethyl)aminomethane-EDTA buffer at pH 7.0 and eluted with 300 mM
      potassium phosphate solution at pH 10.0. Under optimal condition, a 6.0-cm
      monolithic column provided a capacity of 56 ng DNA with an extraction efficiency
      of 71 +/- 5.2% (X +/- RSD). When the amino silica monolithic column was applied
      to extract genomic DNA from the whole blood of crucian carp, an extraction
      efficiency of 52 +/- 5.6% (X +/- RSD) was obtained by three extractions. Since
      the chaotropic-based sample loading and organic solvent wash steps were avoided
      in this procedure, the purified DNA was suitable for downstream processes such as
      PCR. This amino silica monolithic column was demonstrated to allow rapid and
      efficient DNA purification in microscale.

PMID- 19585531
TI  - Microchip free flow planar reversed phase electrochromatography with monolithic
      stationary phase.
AB  - In this study, microchip free flow planar RP electrochromatography (microFF
      PRPEC) was developed by in situ polymerization of monolithic materials in
      microchamber, and successfully applied for the separation of dyes and proteins.
      Poly(butyle methyacrylate-co-ethylene dimethacrylate) was prepared by UV
      initiated polymerization in a glass microchamber (42 mm long, 23 mm wide, and 28
      microm deep). A mixture of 1-propanol, 1,4-butanediol, and water was chosen as
      porogens, and 1.2% (wt%) 2-acrylamide-2-methyl-propanesulfonic acid (AMPS) was
      added into the polymerization solution to generate EOF. With 30% v/v ACN-15 mM
      Tris-HCl as the mobile phase, rhodamine B and methyl green were separated from
      each other with 400 V transverse voltage applied, and resolution as high as 4.6
      was obtained, much higher than that obtained by microFFE under optimal
      conditions. Furthermore, microFF-PRPEC was also successfully applied into the
      separation of lysozyme and ribonuclease B, and resolution as high as 9.4 was
      obtained. All these results demonstrate that microFF-RPPEC might have great
      potential in the microscale continuous preparation of samples with improved
      resolution compared to microFFE.

PMID- 19585532
TI  - Modification of plant hormone levels and signaling as a tool in plant
      biotechnology.
AB  - Plant hormones are signal molecules, present in trace quantities, that act as
      major regulators of plant growth and development. They are involved in a wide
      range of processes such as elongation, flowering, root formation and vascular
      differentiation. For many years, agriculturists have applied hormones to their
      crops to either increase the yield, or improve the quality of the commercial
      product. Nowadays, the knowledge of hormone biosynthesis, degradation and
      signaling pathways has allowed the utilization of biotechnological tools to
      further improve the main agricultural crops. Natural or artificial mutants, with
      impaired functioning of the corresponding genes, have been adopted because of
      their superior phenotype in specific agricultural traits. In addition, transgenic
      plants have been generated to regulate internal hormone levels, or their
      signaling pathways, resulting in some crops that have revolutionized agriculture.

PMID- 19585533
TI  - Purification of homogeneous forms of fungal peroxygenase.
AB  - Extracellular peroxygenase from the agaric fungus Agrocybe aegerita is a
      versatile biocatalyst that oxygenates various substrates by means of hydrogen
      peroxide. The enzyme is routinely produced in suspensions of soybean meal and has
      until now been purified by several steps of fast protein liquid chromatography
      (FPLC) using different ion exchangers. The final protein fraction had a molecular
      mass of 46 kDa but still consisted of several incompletely separated proteins
      with slightly differing isoelectric points (pI 5.2, 5.6, 6.1), probably
      representing differently glycosylated isoforms. This made it difficult to further
      purify the individual protein forms. Since homogeneous protein fractions are a
      pre-requisite for X-ray crystallography and specific structure-function studies,
      an appropriate FPLC procedure was developed starting with pre-purification of
      crude peroxygenase on SP Sepharose followed by chromatofocusing on a Mono P
      column and elution with a pH gradient. Three sufficiently separated main protein
      peaks were eluted from the Mono P column and confirmed to be distinct forms of
      aromatic peroxygenase with different pIs. All A. aegerita peroxygenase forms
      oxygenated toluene and naphthalene and no catalytic differences were observed
      between them. We tested also two devices for preparative isoelectric focusing
      (Rotofor, IsoPrime systems) for peroxygenase separation but resolution and
      protein recovery were not sufficient.

PMID- 19585535
TI  - High-performance separation of small inorganic anions on a methacrylate-based
      polymer monolith grafted with [2(methacryloyloxy)ethyl] trimethylammonium
      chloride.
AB  - A glycidyl methacrylate-co-ethylene dimethacrylate monolith in capillary format
      (100 microm/id) has been grafted with chains of poly([2(methacryloyloxy)ethyl]
      trimethylammonium chloride (poly-META) and applied to the ion-chromatographic
      separation of selected inorganic anions. Grafting chains of META onto the generic
      monolithic scaffold resulted in a monolith with 'electrolyte responsive flow
      permeability', which manifested as increased permeability in the presence of
      electrolyte solutions. Using an eluent of 2 mM sodium benzoate and on-column
      contactless conductivity detection, a test mixture of six common anions was
      isocratically separated and detected within 12 min, with the first four anions
      baseline resolved within a retention time window of 3.2 min. Retention time
      precision was < or = 1.2% for all anions tested. Separation efficiencies of
      15,000 N/m were achieved for fluoride at 1 microL/min, with column efficiencies
      up to 29,500 N/m obtained at a lower flow rate of 100 nL/min. Furthermore,
      repeatability of the column modification procedure using photografting methods
      was acceptable, with retention times between replicate columns matching within
      9%.

PMID- 19585534
TI  - Production of L-DOPA and dopamine in recombinant bacteria bearing the
      Vitreoscilla hemoglobin gene.
AB  - Given the well-established beneficial effects of Vitreoscilla hemoglobin (VHb) on
      heterologous organisms, the potential of this protein for the production of L
      DOPA and dopamine in two bacteria, Citrobacter freundii and Erwinia herbicola,
      was investigated. The constructed recombinants bearing the VHb gene (vgb(+)) had
      substantially higher levels of cytoplasmic L-DOPA (112 mg/L for C. freundii and
      97 mg/L for E. herbicola) than their respective hosts (30.4 and 33.8 mg/L) and
      the vgb(-) control strains (35.6 and 35.8 mg/L). Further, the vgb(+) recombinants
      of C. freundii and E. herbicola had 20-fold and about two orders of magnitude
      higher dopamine levels than their hosts, repectively. The activity of tyrosine
      phenol-lyase, the enzyme converting L-tyrosine to L-DOPA, was well-correlated to
      cytoplasmic L-DOPA levels. As cultures aged, higher tyrosine phenol-lyase
      activity of the vgb(+) strains was more apparent.

PMID- 19585536
TI  - On-column titration and investigation of metal complex formation for
      aminopolycarboxylate functionalised monoliths using scanning contactless
      conductivity detection.
AB  - The application of scanning capacitively coupled contactless conductivity
      detection (SC(4)D) for the determination of pH dependant behaviour of two
      aminopolycarboxylates immobilised onto the surface of a monolithic capillary
      column is described. The use of SC(4)D to visualise changes in conductivity of
      the discrete zones of functional groups within monolithic capillary columns
      allows for the effects of immobilisation on the physicochemical properties of
      zones to be compared to that of the functional group in solution. The
      perturbation of the pK(a) values of the functional groups can be attributed to
      the change in chemical environment experienced by the functional group through
      the presence of local hydrogen bonding and surface induced effects. These bonds,
      both between adjacent functional groups and with the monolithic polymethacrylate
      scaffold, result in a modification of the electron density on the functional
      group and therefore a change in pK(a). Changes in the pK(a) of N-(2
      acetamido)iminodiacetic acid (ADA) from 2.48 to 5.2 for one of the acidic
      protons, with little change in the pK(a) of the amine group, were observed, which
      correlates to similar changes in aggregated systems of aminopolycarboxylates.
      Similar results were obtained for the iminodiacetic acid (IDA) once immobilised
      onto the surface of the monolith. Furthermore, the ability to measure changes in
      the charge of such discrete zones of functional groups allows for the
      visualisation of complexation events occurring directly on-column, where such
      complexes result in a change in charge of the functional group. This potentially
      useful technique is illustrated within for the formation of aminopolycarboxylate
      complexes with a selection of metal ions.

PMID- 19585537
TI  - The use of self-interaction chromatography in stable formulation and
      crystallization of proteins.
AB  - This paper reviews the basic principles of the recently developed self
      interaction chromatography (SIC) technique with regard to protein solution
      stability and protein crystallization. It gives experimental protocols for both
      normal-scale and micro-scale SIC experiments and reviews recent developments and
      current applications of this novel technique in the biopharmaceutical area. This
      paper aims to be a benchmark in the further proliferation of this highly
      effective and fast technology for the rational design of stable aqueous
      formulations of therapeutic proteins and the determination of solution conditions
      favoring protein crystallization.

PMID- 19585538
TI  - Curry spice curcumin and prostate cancer.

PMID- 19585540
TI  - Workplace aggression and violence: moving forward together.

PMID- 19585539
TI  - Co-activator activator (CoAA) prevents the transcriptional activity of Runt
      domain transcription factors.
AB  - Runx proteins are essential for a number of developmental processes and are
      aberrantly expressed in many human cancers. Runx factors bind DNA and co-factors
      to activate or repress genes crucial for bone formation, hematopoiesis, and
      neuronal development. Co-activator activator (CoAA) is a nuclear protein that
      regulates gene expression, RNA splicing and is overexpressed in many human
      tumors. In this study, we identified CoAA as a Runx2 binding protein. CoAA
      repressed Runx factor-dependent activation of reporter genes in a histone
      deacetylase-independent manner. CoAA also blocked Runx2-mediated repression of
      the Axin2 promoter, a novel Runx target gene. The carboxy-terminus of CoAA is
      essential for binding the Runt domains of Runx1 and Runx2. In electophoretic
      mobility shift assays, CoAA inhibited Runx2 interactions with DNA. These data
      indicate that CoAA is an inhibitor of Runx factors and can negate Runx factor
      regulation of gene expression. CoAA is expressed at high levels in human fetal
      osteoblasts and osteosarcoma cell lines. Suppression of CoAA expression by RNA
      interference reduced osteosarcoma cell viability in vitro, suggesting that it
      contributes to the proliferation and/or survival of osteoblast lineage cells.

PMID- 19585542
TI  - Atomic force microscopy analysis of central nervous system cell morphology on
      silicon carbide and diamond substrates.
AB  - Brain machine interface (BMI) devices offer a platform that can be used to assist
      people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and
      Parkinson's disease. Silicon (Si) has been the material of choice used for the
      manufacture of BMI devices due to its mechanical strength, its electrical
      properties and multiple fabrication techniques; however, chronically implanted
      BMI devices have usually failed within months of implantation due to
      biocompatibility issues and the fact that Si does not withstand the harsh
      environment of the body. Single crystal cubic silicon carbide (3C-SiC) and
      nanocrystalline diamond (NCD) are semiconductor materials that have previously
      shown good biocompatibility with skin and bone cells. Like Si, these materials
      have excellent physical characteristics, good electrical properties, but unlike
      Si, they are chemically inert. We have performed a study to evaluate the general
      biocompatibility levels of all of these materials through the use of in vitro
      techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were
      used for the study, and polystyrene (PSt) and amorphous glass were used as
      controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5
      Diphenyltetrazolium Bromide] assays were performed to determine general cell
      viability with each substrate and atomic force microscopy (AFM) was used to
      quantify the general cell morphology on the substrate surface along with the
      substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate
      tested to have good viability and superior lamellipodia permissiveness with both
      cell lines, while NCD showed a good level of viability with the neural H4 line
      but a poor viability with the PC12 line and lower permissiveness than 3C-SiC.
      Explanations pertaining to the performance of each substrate with both cell lines
      are presented and discussed along with future work that must be performed to
      further evaluate specific cell reactions on these substrates.

PMID- 19585541
TI  - Binding kinetics and activity of human poly(ADP-ribose) polymerase-1 on oligo
      deoxyribonucleotide substrates.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a mammalian enzyme that attaches long
      branching chains of ADP-ribose to specific nuclear proteins, including itself.
      Because its activity in vitro is dependent upon interaction with broken DNA, it
      has been postulated that PARP-1 plays an important role in DNA strand-break
      repair in vivo. The exact mechanism of binding to DNA and the structural
      determinants of binding remain to be defined, but regions of transition from
      single-stranded to double-strandedness may be important recognition sites. Here
      we employ surface plasmon resonance (SPR) to investigate this hypothesis.
      Oligodeoxynucleotide (ODN) substrates that mimic DNA with different degrees of
      single-strandedness were used for measurements of both PARP-1/DNA binding
      kinetics and PARP-1's enzyme activities. We found that binding correlated with
      activity, but was unrelated to single-strandedness of the ODN. Instead, PARP-1
      binding and activity were highest on ODNs that modeled a DNA double-strand break
      (DSB). These results provide support for PARP-1 recognizing and binding DSBs in a
      manner that is independent of single-stranded features, and demonstrate the
      usefulness of SPR for simultaneously investigating both PARP-1 binding and PARP-1
      auto-poly(ADP-ribosyl)ation activities within the same in vitro system.

PMID- 19585543
TI  - Parents' safety beliefs and childhood agricultural injury.
AB  - BACKGROUND: This study examined potential associations between parental safety
      beliefs and children's chore assignments or risk of agricultural injury. METHODS:
      Analyses were based on nested case-control data collected by the 1999 and 2001
      Regional Rural Injury Study-II (RRIS-II) surveillance efforts. Cases (n = 425,
      reporting injuries) and controls (n = 1,886, no injuries; selected using
      incidence density sampling) were persons younger than 20 years of age from
      Midwestern agricultural households. A causal model served as the basis for
      multivariate data analysis. RESULTS: Decreased risks of injury (odds ratio [OR]
      and 95% confidence intervals [CI]) were observed for working-aged children with
      "moderate," compared to "very strict" parental monitoring (0.60; 0.40-0.90), and
      with parents believing in the importance of physical (0.80; 0.60-0.95) and
      cognitive readiness (0.70, 0.50-0.90, all children; 0.30, 0.20-0.50, females)
      when assigning new tasks. Parents' safety beliefs were not associated with chore
      assignments. CONCLUSIONS: Parents' safety beliefs were associated with reduced
      risk of childhood agricultural injury; the association was not mediated by chore
      assignments.

PMID- 19585544
TI  - Neurological mortality among U.S. veterans of the Persian Gulf War: 13-year
      follow-up.
AB  - BACKGROUND: This study focuses on long-term mortality, specifically brain cancer,
      amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis
      (MS) of 621,902 veterans who served in the 1990-1991 Persian Gulf War (GW), and
      746,248 non-GW veterans. METHODS: Follow-up began with the date the veteran left
      the GW theater or May 1, 1991 and ended with the date of death or December 31,
      2004. Cox proportional hazard models were used for analyses. RESULTS: Adjusted
      mortality rate ratios (aRR) of GW veterans compared to non-GW veterans were not
      statistically significant for brain cancer (aRR = 0.90, 95% confidence interval
      (CI): 0.73, 1.11), MS (aRR = 0.61, 95% CI: 0.23, 1.63), Parkinson's disease (aRR
      = 0.71, 95% CI: 0.17, 2.99), or ALS (aRR = 0.96, 95% CI: 0.56, 1.62). GW veterans
      potentially exposed to nerve agents for 2 or more days and GW veterans exposed to
      oil well fire smoke were at increased risk for brain cancer mortality (aRR =
      2.71, 95% CI: 1.25, 5.87; aRR = 1.81, 95% CI: 1.00, 3.27; respectively).
      CONCLUSIONS: The risk of death due to ALS, MS, Parkinson's disease, and brain
      cancer was not associated with 1991 GW service in general. However, GW veterans
      potentially exposed to nerve agents at Khamisiyah, Iraq, and to oil well fire
      smoke had an increased risk of mortality due to brain cancer.

PMID- 19585545
TI  - Immigration, employment relations, and health: Developing a research agenda.
AB  - BACKGROUND: International migration has emerged as a global issue that has
      transformed the lives of hundreds of millions of persons. Migrant workers
      contribute to the economic growth of high-income countries often serving as the
      labour force performing dangerous, dirty and degrading work that nationals are
      reluctant to perform. METHODS: Critical examination of the scientific and "grey"
      literatures on immigration, employment relations and health. RESULTS: Both lay
      and scientific literatures indicate that public health researchers should be
      concerned about the health consequences of migration processes. Migrant workers
      are more represented in dangerous industries and in hazardous jobs, occupations
      and tasks. They are often hired as labourers in precarious jobs with poverty
      wages and experience more serious abuse and exploitation at the workplace. Also,
      analyses document migrant workers' problems of social exclusion, lack of health
      and safety training, fear of reprisals for demanding better working conditions,
      linguistic and cultural barriers that minimize the effectiveness of training,
      incomplete OHS surveillance of foreign workers and difficulty accessing care and
      compensation when injured. Therefore migrant status can be an important source of
      occupational health inequalities. CONCLUSIONS: Available evidence shows that the
      employment conditions and associated work organization of most migrant workers
      are dangerous to their health. The overall impact of immigration on population
      health, however, still is poorly understood and many mechanisms, pathways and
      overall health impact are poorly documented. Current limitations highlight the
      need to engage in explicit analytical, intervention and policy research.

PMID- 19585546
TI  - Protein dynamics and conformational disorder in molecular recognition.
AB  - Recognition requires protein flexibility because it facilitates conformational
      rearrangements and induced-fit mechanisms upon target binding. Intrinsic disorder
      is an extreme on the continuous spectrum of possible protein dynamics and its
      role in recognition may seem counterintuitive. However, conformational disorder
      is widely found in many eukaryotic regulatory proteins involved in processes such
      as signal transduction and transcription. Disordered protein regions may in fact
      confer advantages over folded proteins in binding. Rapidly interconverting and
      diverse conformers may create mean electrostatic fields instead of presenting
      discrete charges. The resultant "polyelectrostatic" interactions allow for the
      utilization of post-translational modifications as a means to change the net
      charge and thereby modify the electrostatic interaction of a disordered region.
      Plasticity of disordered protein states enables steric advantages over folded
      proteins and allows for unique binding configurations. Disorder may also have
      evolutionary advantages, as it facilitates alternative splicing, domain shuffling
      and protein modularity. As proteins exist in a continuous spectrum of disorder,
      so do their complexes. Indeed, disordered regions in complexes may control the
      degree of motion between domains, mask binding sites, be targets of post
      translational modifications, permit overlapping binding motifs, and enable
      transient binding of different binding partners, making them excellent candidates
      for signal integrators and explaining their prevalence in eukaryotic signaling
      pathways. "Dynamic" complexes arise if more than two transient protein interfaces
      are involved in complex formation of two binding partners in a dynamic
      equilibrium. "Disordered" complexes, in contrast, do not involve significant
      ordering of interacting protein segments but rely exclusively on transient
      contacts. The nature of these interactions is not well understood yet but
      advancements in the structural characterization of disordered states will help us
      gain insights into their function and their implications for health and disease.

PMID- 19585547
TI  - Adding a single CA 125 measurement to ultrasound imaging performed by an
      experienced examiner does not improve preoperative discrimination between benign
      and malignant adnexal masses.
AB  - OBJECTIVES: To determine whether CA 125 measurement is superior to ultrasound
      imaging performed by an experienced examiner for discriminating between benign
      and malignant adnexal lesions, and to determine whether adding CA 125 to
      ultrasound examination improves diagnostic performance. METHODS: This is a
      prospective multicenter study (International Ovarian Tumor Analysis (IOTA) study)
      conducted in nine European ultrasound centers in university hospitals. Of 1149
      patients with an adnexal mass examined in the IOTA study, 83 were excluded. Of
      the remaining 1066 patients, 809 had CA 125 results available and were included.
      The patients underwent preoperative serum CA 125 measurements and transvaginal
      ultrasound examination by an experienced ultrasound examiner blinded to CA 125
      values. The examiner classified each mass as certainly or probably benign,
      difficult to classify, or probably or certainly malignant. The outcome measure
      was the sensitivity and specificity with regard to malignancy of CA 125,
      ultrasound imaging and their combined use, the 'gold standard' being the
      histological diagnosis of the adnexal mass removed surgically within 120 days
      after the ultrasound examination. RESULTS: There were 242 (30%) malignancies. For
      534 tumors judged to be certainly benign or certainly malignant by the ultrasound
      examiner the sensitivity and specificity of ultrasound examination and CA 125 (>
      or =35 U/mL indicating malignancy) were 97% vs. 86% (95% CI of difference, 4.7
      17.2) and 99% vs. 79% (95% CI of difference, 15.7-24.2); for 209 tumors judged
      probably benign or probably malignant, sensitivity and specificity were 81% vs.
      57% (95% CI of difference, 12.3-36.0) and 91% vs. 74% (95% CI of difference, 8.5
      25.7); for 66 tumors that were difficult to classify, sensitivity and specificity
      were 57% vs. 39% (95% CI of difference, -9.7 to 41.1) and 74% vs. 67% (95% CI of
      difference, -14.6 to 27.7). Diagnostic performance deteriorated when CA 125 was
      used as a second-stage test after ultrasound examination. CONCLUSIONS: Specialist
      ultrasound examination is superior to CA 125 for preoperative discrimination
      between benign and malignant adnexal masses, irrespective of the diagnostic
      confidence of the ultrasound examiner; adding CA 125 to ultrasound does not
      improve diagnostic performance. Our results indicate that greater investment in
      education and training in gynecological ultrasound imaging would be of value.

PMID- 19585549
TI  - Large liver cell change in hepatitis B virus-related liver cirrhosis.
AB  - Large liver cell change (LLCC) refers to microscopic lesions often found in
      various chronic liver diseases; however, its nature is still controversial.
      Thirty-four formalin-fixed and 19 fresh frozen hepatitis B virus (HBV)-related
      cirrhosis samples were examined for the presence of LLCC, small liver cell change
      (SLCC), and hepatocellular carcinoma (HCC). The cell cycle checkpoint status
      (p21, p27, p16, Tp53), cell dynamics (proliferating cell nuclear antigen, Ki-67,
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling,
      M30), DNA damage (gamma-H2AX [H2A histone family, member X]), telomere lengths,
      chromosomal instability (micronuclei index), and senescence-associated beta
      galactosidase (SA-beta-Gal) activity were evaluated using an in situ approach and
      compared to those in normal liver (n = 5) and liver with chronic cholestasis (34
      cases of hepatolithiasis and three cases of primary biliary cirrhosis). In HBV
      related cirrhosis, the p21, p27, and p16 cell cycle checkpoint markers were
      activated in normal-looking cirrhotic hepatocytes (NLCH), but diminished
      gradually from LLCC, SLCC, to HCC, with an increase in Tp53 expression. There was
      a general decrease in telomere length from NLCH, LLCC, SLCC, to HCC. Micronuclei,
      gamma-H2AX foci, and net cellular gain were significantly increased from normal
      hepatocytes, NLCH, LLCC, SLCC, to HCC. The SA-beta-Gal activity was weaker in
      LLCC compared to NLCH and absent in SLCC and HCC. In contrast, cholestatic LLCC
      showed retained expression of cell cycle checkpoint markers and decreased net
      cellular gain compared to adjacent normal-looking hepatocytes. HBV-related LLCC
      showed significantly higher Tp53 labeling index, gamma-H2AX labeling index, and
      micronuclei index; shorter telomere length; decreased SA-beta-Gal activity; and
      increased net cellular gain compared to cholestatic LLCC. CONCLUSION: The nature
      of LLCC is rather heterogeneous depending on the biological setting. The
      characteristics of HBV-related LLCC are more consistent with dysplastic rather
      than merely reactive hepatocytes, whereas cholestatic LLCC more likely represents
      reactive change with more stringent cell cycle checkpoint control.

PMID- 19585548
TI  - High-dose ursodeoxycholic acid for the treatment of primary sclerosing
      cholangitis.
AB  - Previous controlled trials are inconclusive regarding the efficacy of
      ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC).
      One hundred fifty adult patients with PSC were enrolled in a long-term,
      randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day)
      versus placebo. Liver biopsy and cholangiography were performed before
      randomization and after 5 years. The primary outcome measures were development of
      cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The
      study was terminated after 6 years due to futility. At enrollment, the UDCA (n =
      76) and placebo (n = 74) groups were similar with respect to sex, age, duration
      of disease, serum aspartate aminotransferase and alkaline phosphatase levels,
      liver histology, and Mayo risk score. During therapy, aspartate aminotransferase
      and alkaline phosphatase levels decreased more in the UDCA group than the placebo
      group (P < 0.01), but improvements in liver tests were not associated with
      decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%)
      versus 19 patients in the placebo group (26%) had reached one of the pre
      established clinical endpoints. After adjustment for baseline stratification
      characteristics, the risk of a primary endpoint was 2.3 times greater for
      patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for
      death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse
      events were more common in the UDCA group than the placebo group (63% versus 37%
      [P < 0.01]). CONCLUSION: Long-term, high-dose UDCA therapy is associated with
      improvement in serum liver tests in PSC but does not improve survival and was
      associated with higher rates of serious adverse events.

PMID- 19585550
TI  - Long-term reduction of jaundice in Gunn rats by nonviral liver-targeted delivery
      of Sleeping Beauty transposon.
AB  - Asialoglycoprotein receptor (ASGPR)-mediated endocytosis has been used to target
      genes to hepatocytes in vivo. However, the level and duration of transgene
      expression have been low because of lysosomal translocation and degradation of
      the DNA and lack of its integration into the host genome. In this study we
      packaged the DNA of interest in proteoliposomes containing the fusogenic
      galactose-terminated F-glycoprotein of the Sendai virus (FPL) for targeted
      delivery to hepatocytes. After the FPL binds to ASGPR on the hepatocyte surface,
      fusogenic activity of the F-protein delivers the DNA into the cytosol, bypassing
      the endosomal pathway. For transgene integration we designed plasmids containing
      one transcription unit expressing the Sleeping Beauty transposase (SB) and
      another expressing human uridinediphosphoglucuronate glucuronosyltransferase-1A1
      (pSB-hUGT1A1). The latter was flanked by inverted/direct repeats that are
      substrates of SB. In cell culture, FPL-mediated delivery of the E. coli beta
      galactosidase gene (LacZ) resulted in transduction of ASGPR-positive cells (rat
      hepatocytes or Hepa1 cell line), but not of ASGPR-negative 293 cells. Intravenous
      injection of the FPL-entrapped pSB-hUGT1A1 (4-8 microg/day, 1-4 doses) into
      UGT1A1-deficient hyperbilirubinemic Gunn rats (model of Crigler-Najjar syndrome
      type 1) resulted in hUGT1A1 expression in 5%-10% of hepatocytes, but not in other
      cell types. Serum bilirubin levels declined by 30% +/- 4% in 2 weeks and remained
      at that level throughout the 7-month study duration. With histidine containing
      FPL, serum bilirubin was reduced by 40% +/- 5%, and bilirubin glucuronides were
      excreted into bile. No antibodies were detectable in the recipient rats against
      the F-protein or human UGT1A1. CONCLUSION: FPL is an efficient hepatocyte
      targeted gene delivery platform in vivo that warrants further exploration toward
      clinical application.

PMID- 19585551
TI  - Factors influencing antibody stability at solid-liquid interfaces in a high shear
      environment.
AB  - A rotating disk shear device was used to study the effect of interfacial shear on
      the structural integrity of human monoclonal antibodies of IgG4 isotype. Factors
      associated with the solution conditions (pH, ionic strength, surfactant
      concentration, temperature) and the interface (surface roughness) were studied
      for their effect on the rate of IgG4 monomer loss under high shear conditions.
      The structural integrity of the IgG4 was probed after exposure to interfacial
      shear effects by SDS-PAGE, IEF, dynamic light scattering, and peptide mapping by
      LC-MS. This analysis revealed that the main denaturation pathway of IgG4 exposed
      to these effects was the formation of large insoluble aggregates. Soluble
      aggregation, breakdown in primary structure, and chemical modifications were not
      detected. The dominant factors found to affect the rate of IgG4 monomer loss
      under interfacial shear conditions were found to be pH and the nanometer-scale
      surface roughness associated with the solid-liquid interface. Interestingly,
      temperature was not found to be a significant factor in the range tested (15-45
      degrees C). The addition of surfactant was found to have a significant
      stabilizing effect at concentrations up to 0.02% (w/v). Implications of these
      findings for the bioprocessing of this class of therapeutic protein are briefly
      discussed.

PMID- 19585552
TI  - Insulin transport across porous charged membranes: Effect of the electrostatic
      interaction.
AB  - Insulin transport phenomena across a series of porous charged membranes were
      studied at two pH conditions (pH 3.3 and pH 7.4) in this article. The membranes
      were prepared by pore-surface modification of porous poly(acrylonitrile) (PAN)
      membranes by grafting with weak acidic and basic functional groups. The insulin
      partition coefficient K between the membrane and solution was estimated from the
      equilibrium adsorption amount in the batch adsorption experiment. The insulin
      effective diffusion coefficient D inside the membrane was determined as a fitting
      parameter by matching the diffusion model with the experimental data of the
      diffusion measurement. Both K and D correlated well with the charge properties of
      the insulin and membrane: when the insulin and membrane carried opposite net
      charge, the partition coefficient showed relatively larger values, while the
      effective diffusion coefficient was reduced. The insulin permeability coefficient
      P obtained from the experimental results agreed with that estimated from the
      partition coefficient and effective diffusion coefficient. These results
      suggested that the combined effects of the solubility and diffusivity on the
      permeability coefficient complicated the relationship between the permeability
      and the charge properties of the insulin and membrane. Additionally, our
      calculation supported that insulin permeability was reduced by the boundary layer
      between the membrane and solution.

PMID- 19585553
TI  - Reproductive toxicity and pharmacokinetics of di-n-butyl phthalate (DBP)
      following dietary exposure of pregnant rats.
AB  - Most rodent developmental toxicity studies of dibutylphthalate (DBP) have relied
      on bolus gavage dosing. This study characterized the developmental toxicity of
      dietary DBP. Pregnant CD rats were given nominal doses of 0, 100, or 500 mg
      DBP/kg/day in diet (actual intake 0, 112, and 582 mg/kg/day) from gestational day
      (GD) 12 through the morning of GD 19. Rats were killed 4 or 24 hr thereafter. DBP
      dietary exposure resulted in significant dose-dependent reductions in testicular
      mRNA concentration of scavenger receptor class B, member 1; steroidogenic acute
      regulatory protein; cytochrome P450, family 11, subfamily a, polypeptide 1; and
      cytochrome P450 family 17, subfamily a, polypeptide 1. These effects were most
      pronounced 4 hr after the end of exposure. Testicular testosterone was reduced 24
      hr post-exposure in both DBP dose groups and 4 hr after termination of the 500-mg
      DBP/kg/day exposure. Maternal exposure to 500 mg DBP/kg/day induced a significant
      reduction in male offspring's anogenital distance indicating in utero disruption
      of androgen function. Leydig cell aggregates, increased cord diameters, and
      multinucleated gonocytes were present in DBP-treated rats. Monobutyl phthalate,
      the developmentally toxic metabolite of DBP, and its glucuronide conjugate were
      found in maternal and fetal plasma, amniotic fluid, and maternal urine. Our
      results, when compared to previously conducted gavage studies, indicate that
      approximately equal doses of oral DBP exposure of pregnant rats, from diet or
      gavage, result in similar responses in male offspring.

PMID- 19585554
TI  - Use of Xanthinol Nicotinate as a co-treatment for radio- and chemo-therapy in
      experimental tumors.
AB  - The tumor micro-environment plays a key role in the tumor resistance to cytotoxic
      treatments. It has been demonstrated that it is possible to modulate the tumor
      microenvironment to potentiate anti-cancer therapy. Here, we made the hypothesis
      that the vasoactive agent xanthinol nicotinate (XN) could be an important
      modulator of the tumor perfusion and oxygenation. Using functional non invasive
      techniques (in vivo EPR oximetry and dynamic contrast enhanced MRI), we were able
      to define a time window in which tumor oxygenation, flow and permeability were
      significantly increased in the TLT tumor model implanted in muscles of mice. As a
      consequence of the alleviation of tumor hypoxia, we found out that XN was able to
      radiosensitize the tumors when applying 10 Gy of X-Rays during the reoxygenation
      of the tumors (enhancement in radiation response of 1.4). Moreover, the
      administration of cyclosphosphamide (50 mg/kg) used as a chemotherapeutic agent
      was more efficient when applying the treatment after XN administration
      (enhancement in response to chemotherapy of 2.7). These results show the
      importance of the dynamic evolution of the tumor microenvironment on the response
      to treatments, and that XN is an efficient modulator of the tumor hemodynamics
      that may potentiate cytotoxic treatments.

PMID- 19585556
TI  - Relationships between critical period of estrogen exposure and circulating levels
      of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case
      control study.
AB  - Epidemiological observations suggest that insulin-like growth factor-I (IGF-I), a
      potent mitogenic and anti-apoptotic peptide, plays a role in the etiology of
      breast cancer. Estrogen, which is crucial in breast carcinogenesis, both
      regulates and is influenced by IGF-I family. A case-control study was conducted
      to assess the role of IGF-I as a biomarker for breast cancer and to evaluate the
      potential joint effect of circulating IGF-I and critical period of estrogen
      exposure, as estimated by the interval between age at menarche and age at first
      full-term pregnancy on the risk of breast cancer. Questionnaire information and
      blood samples were taken before treatment from 297 incident cases with breast
      cancer and 593 controls admitted for health examination at the Tri-Service
      General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF-I and IGFBP
      3 were measured by immunoradiometric assay. Conditional logistic regression was
      used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our
      case-control data indicate that breast cancer risk related to IGF-I differs
      according to menopausal status. High circulating levels of IGF-I increased risk
      of pre- but not postmenopausal breast cancer (top vs. bottom tertile, adjusted
      OR, 1.86; 95% CI, 1.01-3.44). Furthermore, elevated IGF-I concentrations in
      conjunction with prolonged interval of critical period of estrogen exposure were
      associated with significantly increased risk of breast cancer, particularly among
      estrogen-positive cases (adjusted OR, 2.42, 95% CI, 1.33-4.38). These results
      suggest that the joint effect of IGF-I and estrogens may provide novel methods of
      breast cancer risk reduction among women.

PMID- 19585555
TI  - Relationship between dietary and supplemental intake of folate, methionine,
      vitamin B6 and folate receptor alpha expression in ovarian tumors.
AB  - Because folate receptor alpha (FRalpha) is frequently over-expressed in
      epithelial ovarian tumors, we hypothesized that its association with folate may
      differ by FRalpha expression or by the timing of intake. We examined the
      association between folate and other cofactors in 152 ovarian cancers evaluated
      for FRalpha expression from the Nurses' Health Study. Multivariate odds ratios
      (ORs) and 95% confidence intervals (CIs) were estimated using unconditional
      logistic regression. FRalpha expression was higher in serous invasive and
      advanced stage ovarian tumors. Recent dietary folate intake > or = 300 microg/day
      compared to < 300 microg/day was associated with decreased risk of developing
      ovarian cancer (OR = 0.62; 95%CI 0.40-0.96). There was suggestion of an increased
      risk with total folate (dietary and supplemental) (OR=1.42; 95%CI 0.94-2.14 for
      past and OR = 1.53; 95%CI 0.99-2.37 for recent intake). These results did not
      vary by FRalpha status of the tumor. Methyl group score, a marker of high dietary
      folate and methionine intake but low alcohol consumption, was inversely
      associated with risk of ovarian cancer (OR = 0.44; 95%CI 0.23-0.84 for past and
      OR=0.46; 95%CI 0.24-0.88 for recent intake). There were no clear individual
      associations between methionine, vitamin B(6), or multivitamin use and ovarian
      cancer risk overall or by FRalpha tumor status. Our data do not support the
      hypothesis that the relationship between factors involved in one-carbon
      metabolism and ovarian cancer risk differs by FRalpha status of the tumor.

PMID- 19585557
TI  - Structural and biochemical analyses of YvgN and YtbE from Bacillus subtilis.
AB  - Bacillus subtilis is one of the most studied gram-positive bacteria. In this
      work, YvgN and YtbE from B. subtilis, assigned as AKR5G1 and AKR5G2 of aldo-keto
      reductase (AKR) superfamily. AKR catalyzes the NADPH-dependent reduction of
      aldehyde or aldose substrates to alcohols. YvgN and YtbE were studied by
      crystallographic and enzymatic analyses. The apo structures of these proteins
      were determined by molecular replacement, and the structure of holoenzyme YvgN
      with NADPH was also solved, revealing the conformational changes upon cofactor
      binding. Our biochemical data suggest both YvgN and YtbE have preferential
      specificity for derivatives of benzaldehyde, such as nitryl or halogen group
      substitution at the 2 or 4 positions. These proteins also showed broad catalytic
      activity on many standard substrates of AKR, such as glyoxal, dihydroxyacetone,
      and DL-glyceraldehyde, suggesting a possible role in bacterial detoxification.

PMID- 19585558
TI  - The Global Network for Molecular and Cell Biology (MCBN).

PMID- 19585559
TI  - Osmolyte perturbation reveals conformational equilibria in spin-labeled proteins.
AB  - Recent evidence suggests that proteins at equilibrium can exist in a manifold of
      conformational substates, and that these substates play important roles in
      protein function. Therefore, there is great interest in identifying regions in
      proteins that are in conformational exchange. Electron paramagnetic resonance
      spectra of spin-labeled proteins containing the nitroxide side chain (R1) often
      consist of two (or more) components that may arise from slow exchange between
      conformational substates (lifetimes > 100 ns). However, crystal structures of
      proteins containing R1 have shown that multicomponent spectra can also arise from
      equilibria between rotamers of the side chain itself. In this report, it is shown
      that these scenarios can be distinguished by the response of the system to
      solvent perturbation with stabilizing osmolytes such as sucrose. Thus, site
      directed spin labeling (SDSL) emerges as a new tool to explore slow
      conformational exchange in proteins of arbitrary size, including membrane
      proteins in a native-like environment. Moreover, equilibrium between substates
      with even modest differences in conformation is revealed, and the simplicity of
      the method makes it suitable for facile screening of multiple proteins. Together
      with previously developed strategies for monitoring picosecond to millisecond
      backbone dynamics, the results presented here expand the timescale over which
      SDSL can be used to explore protein flexibility.

PMID- 19585560
TI  - Defining critical inflammatory parameters for endotoxin impurity in manufactured
      alginate microcapsules.
AB  - Since current purification methods cannot completely remove all traces of
      endotoxin in biomaterials intended for use in implantable or blood-contacting
      devices, acceptable levels of endotoxin contamination that will not cause a
      significant inflammatory reaction need to be defined. Inflammatory reactions to
      biomaterials may include production of high concentrations of potentially harmful
      nitric oxide (NO) generated by macrophages. Nitrite accumulation was measured
      from RAW264.7 cells treated with either lipopolysaccharide (LPS) free in solution
      or defined quantities of LPS incorporated into alginate in the absence or
      presence of murine interferon-gamma (mrIFN-gamma). In the absence of IFN-gamma,
      significant NO production by RAW 264.7 cells occurred for LPS levels down to
      0.018 EU/mL. In the presence of mrIFN-gamma, the lowest concentration of LPS
      tested in solution (0.006 EU/mL) elicited a significant increase in NO
      production. In the absence or presence of mrIFN-gamma, five times the
      concentration of LPS incorporated into alginate as compared to LPS free in
      solution was necessary to elicit a similar NO response by RAW264.7. These results
      demonstrate that very low concentrations of endotoxin can elicit significant NO
      responses from macrophages, particularly when inflammatory cytokines are present.
      Biomaterials may sequester endotoxin, resulting in lower inflammatory reactions
      that otherwise might be expected.

PMID- 19585561
TI  - Bioencapsulation of apomyoglobin in nanoporous organosilica sol-gel glasses:
      influence of the siloxane network on the conformation and stability of a model
      protein.
AB  - Nanoporous sol-gel glasses were used as host materials for the encapsulation of
      apomyoglobin, a model protein employed to probe in a rational manner the
      important factors that influence the protein conformation and stability in silica
      based materials. The transparent glasses were prepared from tetramethoxysilane
      (TMOS) and modified with a series of mono-, di- and tri-substituted
      alkoxysilanes, R(n)Si(OCH(3))(4-n) (R = methyl-, n = 1; 2; 3) of different molar
      content (5, 10, 15%) to obtain the decrease of the siloxane linkage (-Si-O-Si-).
      The conformation and thermal stability of apomyoglobin characterized by circular
      dichroism spectroscopy (CD) was related to the structure of the silica host
      matrix characterized by (29)Si MAS NMR and N(2) adsorption. We observed that the
      protein transits from an unfolded state in unmodified glass (TMOS) to a native
      like helical state in the organically modified glasses, but also that the
      secondary structure of the protein was enhanced by the decrease of the siloxane
      network with the methyl modification (n = 0 < n = 1 < n = 2 < n = 3; 0 < 5 < 10 <
      15 mol %). In 15% trimethyl-modified glass, the protein even reached a maximum
      molar helicity (-24,000 deg. cm(2) mol(-1)) comparable to the stable folded heme
      bound holoprotein in solution. The protein conformation and stability induced by
      the change of its microlocal environment (surface hydration, crowding effects,
      microstructure of the host matrix) were discussed owing to this trend dependency.
      These results can have an important impact for the design of new efficient
      biomaterials (sensors or implanted devices) in which properly folded protein is
      necessary.

PMID- 19585562
TI  - Inactivation of Staphylococcus aureus in calcium phosphate biomaterials via
      isostatic compression.
AB  - High hydrostatic pressure is currently used as a sterilization technique in
      agroalimentary field. This study explores the potential use of high pressure for
      bacterial inactivation of bone substitute calcium phosphate materials.
      Staphylococcus aureus strain incorporated in calcium phosphate powder was
      subjected to isostatic compression. Several parameters of compression were
      tested: application of pressure, time of plateau, number of compressions, and
      waiting time between two compressions. The results showed that the efficacy of
      compression increased with applied pressure and that time of plateau did not play
      an important role. The number of compressions influenced the efficiency of the
      technique and it was necessary to allow ample time between two compressions for
      bacteria to sufficiently multiply. The most effective protocol for preventing the
      growth of S. aureus in calcium phosphate involved two compressions of 5 minutes
      each at 140 MPa spaced at a 24-hour interval.

PMID- 19585563
TI  - Controlling biological interfaces on the nanometer length scale.
AB  - A number of techniques currently exist that allow researchers to generate
      spatially resolved patterns of chemistry and topography on the nanometer length
      scale. Both chemically and topographically nanopatterned surfaces can be
      generated to more accurately mimic the natural extracellular environment.
      Chemically patterned surfaces can also be used to study tightly controlled and
      highly specific cell-cell and cell-substrate interactions or to create
      increasingly densely packed biosensors. From a biological standpoint, these
      methods enable fabrication of elaborate interfaces to mechanistically study the
      effects of cell adhesion ligand density, spacing, clustering, and spatial
      distribution on cell fate and function. The most commonly used nanopatterning
      techniques in the biomaterials arena are reviewed here, including scanning probe,
      electron beam, colloidal, and imprint lithographies, critically examining the
      resolution available and the scalability of the technique for generating the
      number of surfaces necessary for statistically relevant cell culture studies.

PMID- 19585564
TI  - Sequential BMP-2/BMP-7 delivery from polyester nanocapsules.
AB  - The aim of this study was to develop a nanosized, controlled growth factor
      release system to incorporate into tissue engineering scaffolds and thus activate
      the cells seeded in the scaffold. Nanocapsules of poly(lactic acid-co-glycolic
      acid) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were loaded
      with the bone morphogenetic proteins BMP-2 and BMP-7, respectively, and with
      bovine serum albumin (BSA), the model protein. BSA-loading efficiency and release
      kinetics were used to determine the most appropriate nanocapsule pair to achieve
      the delivery of growth factors in a sequential manner, as occurs in natural
      processes. BSA-encapsulation efficiency was highest when the polymer
      concentration used in the preparation of PLGA and PHBV nanocapsules was 10% (w/v)
      (84.75% and 16.72%, respectively). Release of BSA was faster from PLGA than it
      was from PHBV. Based on the encapsulation efficiency and release data, 10% PLGA
      and 10% PHBV nanocapsules were chosen to provide the early BMP-2 and later BMP-7
      release, respectively. Simultaneous, sequential delivery and individual release
      of the BMPs were studied for 7, 14, and 21 days, using rat bone marrow
      mesenchymal stem cells. Individual BMP-2 release suppressed cell proliferation
      while providing higher alkaline phosphatase activity with respect to BMP-7. The
      sequential delivery of BMP-2 and BMP-7 provided slightly lower proliferation than
      did simultaneous delivery, but the highest alkaline phosphatase activity of all
      indicated a synergistic effect on the osteogenic differentiation of mesenchymal
      stem cells caused by the use of the two growth factors in a sequential fashion.

PMID- 19585565
TI  - alpha-Smooth muscle actin-expressing cells and lubricin in periprosthetic tissue.
AB  - The objective of the study was to evaluate the distributions of (1) cells
      expressing the contractile actin isoform, alpha-smooth muscle actin (alpha-SMA)
      and (2) a lubricating and antiadhesion glycoprotein, lubricin, in the tissue
      around loose joint replacement prostheses in human subjects. Periprostehtic
      tissue resected at revision arthroplasty of noncemented glenoid components of
      total shoulder arthroplasties was obtained from 10 patients. Samples of
      periprosthetic tissue were stained with monoclonal antibodies to alpha-SMA and
      lubricin. alpha-SMA was found in cells, principally of fibroblast morphology, in
      many of the fields of view (FOVs) in samples from all patients. Moderate
      correlations were observed between the percentage of FOVs containing alpha-SMA
      expressing cells and the percentages of FOVs containing polyethylene (R(2) =
      0.79) and metallic (R(2) = 0.75) particles. Lubricin was identified (1) as a
      discrete layer on the surface, (2) within the extracellular matrix, and (3)
      intracellularly. These lubricin-positive features were found in samples from all
      patients. Strong correlations were noted between the percentages of FOVs with
      matrix and intracellular lubricin staining (R(2) = 0.97) and between the
      percentages of FOVs with surface and matrix staining for lubricin (R(2) = 0.96).
      Having established the presence of alpha-SMA and lubricin in periprosthetic
      tissue, hypotheses regarding their role in the development and persistence of
      periprosthetic tissue can be synthesized for future study: for example, alpha-SMA
      enabled contracture of the fibrous periprosthetic tissue results in its
      densification, and lubricin-coated surfaces interfere with integrative repair
      processes necessary for resorption and remodeling.

PMID- 19585566
TI  - Poly(methacrylic acid-co-methyl methacrylate) beads promote vascularization and
      wound repair in diabetic mice.
AB  - Topical application of beads made from poly(methacrylic acid-co-methyl
      methacrylate) (45 mol % methacrylic acid, MAA) increased the number of blood
      vessels and improved 1.5 x 1.5 cm full thickness wound closure in a diabetic
      mouse (db/db) model. Three groups were compared: MAA beads, control poly(methyl
      methacrylate) beads (PMMA), and no bead blanks. MAA bead treatment significantly
      increased percent wound closure at all timepoints (7, 14, and 21 days) with MAA
      bead-treated wounds almost closed at day 21 (91 +/- 5.4% MAA vs. 79 +/- 3.2% PMMA
      or 76 +/- 4.8% no beads; p < 0.05). This was consistent with the expected
      significant increase in vascularity in the MAA group at days 7 and 14. For
      example at day 14, MAA bead-treated wounds had a vascular density of 22.7 +/- 2.6
      vessels/hpf compared with 17.0 +/- 2.0 vessels/hpf in the PMMA bead group (p <
      0.05). Epithelial gap and migration measurements suggested that the increased
      vascularity leads to enhanced epithelial cell migration as a principal means of
      wound closure. Although studies are underway to elucidate the mechanism of this
      angiogenic response, the results presented here support the notion that such
      materials, perhaps in other forms, may be useful in wound care or in other
      situations where vascularity is to be enhanced without the use of exogenous
      growth factors.

PMID- 19585567
TI  - Surface-induced cell signaling events control actin rearrangements and motility.
AB  - Understanding the interrelationship between material surface properties and the
      biological response to such materials remains a fundamental scientific challenge,
      as well as being of considerable practical importance in medicine. Through the
      use of a homologous series of copolymers of increasing hydrophobicity, we aimed
      to illuminate the interplay between material surface hydrophobicity and
      signalling events within cells in contact with this model system. Extending
      previous work, we hereby unravel key pathways controlling cell motility and the
      formation of a stellate phenotype, following interaction with polymer-coated
      surfaces. We reveal a comparative increase in cellular motility with increasing
      surface hydrophilicity, conjoint with an arrest in cell cycle progression. We
      also show an anomalous turnover of actin within the cell as a function of
      changing surface hydrophobicity. Finally, we show that cyclic adenosine
      monophosphate may be an effector of the cellular phenotype, as its production is
      increased in response to changes in the surface properties. These results
      highlight important signaling events which control actin rearrangements and the
      subsequent motility and its effectors.

PMID- 19585569
TI  - Engaging with plastination and the Body Worlds phenomenon: a cultural and
      intellectual challenge for anatomists.
AB  - Body Worlds, the international plastination phenomenon, has proved immensely
      popular with audiences worldwide. Never before has the human body been exposed to
      public gaze in such an accessible and intriguing manner. Dissected body parts
      feature alongside whole-body plastinates with their life-like poses ranging from
      those with Renaissance motifs to others with highly contemporary themes. However,
      the exhibitions and their creator, Gunther von Hagens, have astounded many,
      including anatomists, some of whom find the unconventional display of human
      bodies unethical and offensive. The voyeuristic nature of Body Worlds and the
      uneasy balance between entertainment and education have proved problematic for
      anatomists. Von Hagens himself is a polarizing figure, pursuing his dream of
      "democratizing anatomy" with little regard for the conventions of academia. While
      valid ethical objections can be raised against some aspects of the exhibitions,
      we argue that wholesale rejection of them is unwarranted. In arriving at this
      conclusion we assess the ethical and educational issues involved. We divide the
      whole-body plastinates into four categories, ranging from those illustrating
      structural and functional relationships to those with artistic and humanistic
      aspirations rather than anatomical ones. We conclude that anatomists need to face
      up to the opportunities and challenges posed by the Body Worlds phenomenon,
      utilizing what is being presented to the general public and adapting this in
      teaching and research.

PMID- 19585568
TI  - Interplay of anionic charge, poly(ethylene glycol), and iodinated tyrosine
      incorporation within tyrosine-derived polycarbonates: Effects on vascular smooth
      muscle cell adhesion, proliferation, and motility.
AB  - Regulation of smooth muscle cell adhesion, proliferation, and motility on
      biomaterials is critical to the performance of blood-contacting implants and
      vascular tissue engineering scaffolds. The goal of this study was to examine the
      underlying substrate-smooth muscle cell response relations, using a selection of
      polymers representative of an expansive library of multifunctional, tyrosine
      derived polycarbonates. Three chemical components within the polymer structure
      were selectively varied through copolymerization: (1) the content of iodinated
      tyrosine to achieve X-ray visibility; (2) the content of poly(ethylene glycol)
      (PEG) to decrease protein adsorption and cell adhesivity; and (3) the content of
      desaminotyrosyl-tyrosine (DT), which regulates the rate of polymer degradation.
      Using quartz crystal microbalance with dissipation, we quantified differential
      serum protein adsorption behavior because of the chemical components DT,
      iodinated tyrosine, and PEG: increased PEG content within the polymer structure
      progressively decreased protein adsorption but the simultaneous presence of both
      DT and iodinated tyrosine reversed the effects of PEG. The complex interplay of
      these components was next tested on the adhesion, proliferation, and motility
      behavior cultured human aortic smooth muscle cells. The incorporation of PEG into
      the polymer reduced cell attachment, which was reversed in the presence of
      iodinated tyrosine. Further, we found that as little as 10% DT content was
      sufficient to negate the PEG effect in polymers containing iodinated tyrosine,
      whereas in non-iodinated polymers, the PEG effect on cell attachment was
      reversed. Cross-functional analysis of motility and proliferation revealed
      divergent substrate chemistry related cell response regimes. For instance, within
      the series of polymers containing both iodinated tyrosine and 10% of DT,
      increasing PEG levels lowered smooth muscle cell motility without a change in the
      rate of cell proliferation. In contrast, for non-iodinated tyrosine and 10% of
      DT, increasing PEG levels increased cell proliferation significantly while
      reducing cell motility. Clearly, the polycarbonate polymer library offers a
      sensitive platform to modulate cell adhesion, proliferation, and motility
      responses, which, in turn, may have implications for controlling vascular
      remodeling in vivo. Additionally, our data suggests unique biorelevant properties
      following the incorporation of iodinated subunits in a polymeric biomaterial as a
      potential platform for X-ray visible devices.

PMID- 19585570
TI  - Cell confinement in patterned nanoliter droplets in a microwell array by wiping.
AB  - Cell patterning is useful for a variety of biological applications such as tissue
      engineering and drug discovery. In particular, the ability to localize cells
      within distinct fluids is beneficial for a variety of applications ranging from
      microencapsulation to high-throughput analysis. However, despite much progress,
      cell immobilization and maintenance within patterned microscale droplets remains
      a challenge. In particular, no method currently exists to rapidly seed cells into
      microwell arrays in a controllable and reliable manner. In this study, we present
      a simple wiping technique to localize cells within arrays of polymeric
      microwells. This robust method produces cell seeding densities that vary
      consistently with microwell geometry and cell concentration. Moreover, we develop
      a simple theoretical model to accurately predict cell seeding density and seeding
      efficiency in terms of the design parameters of the microwell array and the cell
      density. This short-term cell patterning approach is an enabling tool to develop
      new high-throughput screening technologies that utilize microwell arrays
      containing cells for screening applications.

PMID- 19585571
TI  - Effect of bioactive glass crystallization on the conformation and bioactivity of
      adsorbed proteins.
AB  - Protein adsorption onto the surface of a biomaterial mediates cell adhesion and
      enhances tissue-implant integration. In a previous study, we demonstrated that
      crystallization of bioactive glass (BG) significantly increased the negative zeta
      potential and decreased serum protein adsorption onto the material surface. In
      this study, the conformation of protein adsorbed onto the surface of amorphous
      bioactive glass (ABG) and crystallized bioactive glass (CBG) was analyzed and
      correlated to bone marrow mesenchymal stem cell adhesion and spreading. ABG and
      CBG were immersed in three different protein solutions containing 10% fetal
      bovine serum, bovine serum albumin (BSA), and fibronectin (FN) for 4 h at 37
      degrees C. Grazing angle Fourier transform infrared spectroscopy (GA-FTIR)
      demonstrated that the ratio of (amide I)/(amide II) functional groups of all
      proteins adsorbed onto ABG was greater than that for proteins adsorbed onto CBG.
      The Gaussian curve fitting analysis suggests that the significant expression of
      amide I, rich in charged and flexible unordered secondary structure of adsorbed
      FN, stimulated bone cell adhesion and spreading on the surface of ABG. CBG
      enforces protein conformation that exposes amide II, rich in neutral and stable
      beta-sheet structure and alpha-helix, which limited cell adhesion and spreading.
      Although ABG adsorbed significantly higher quantity of BSA than FN, GA-FTIR
      analyses showed that the ratio of amide I/amide II was significantly higher for
      adsorbed FN. Therefore, the intensity of amide I or amide II bands cannot be
      taken as a measure of the quantity of adsorbed protein.

PMID- 19585573
TI  - Use of an expanded gold standard to estimate the accuracy of colposcopy and
      visual inspection with acetic acid.
AB  - We estimate the accuracy of colposcopy and visual inspection with acetic acid
      (VIA) while minimizing the effects of misclassification bias, and maximizing
      ascertainment of disease. VIA was performed by experienced physicians on a
      population-based sample of women aged 30 to 49 years in rural Shanxi province,
      China. Each woman received VIA, liquid-based cytology (LBC) and hybrid capture 2
      (hc2, QIAGEN, Gaithersburg, MD; formerly Digene Corporation). Any woman who
      tested positive on any test had colposcopy, endocervical curettage (ECC) with
      directed biopsies as necessary and 4-quadrant random biopsies from normal
      appearing areas of the cervix. A standard diagnosis based on colposcopy and
      directed biopsy, and an expanded diagnosis including ECC and 4-quadrant random
      biopsy were generated for each woman. In 1,839 women, use of the expanded versus
      the standard diagnostic criteria increased the prevalence of histologically
      confirmed high-grade cervical intraepithelial neoplasia and cancer (CIN2+) from
      3.2% (59/1,839) to 4.2% (77/1,839) and decreased the sensitivity of VIA for CIN2+
      from 69.5% (95% CI: 56.8-79.8) to 58.4% (95% CI: 47.3-68.8%) with little change
      in specificity of approximately 89%. Compared with the expanded diagnostic
      criterion, the sensitivity of a visual diagnosis of high-grade CIN or cancer by a
      colposcopist was 49.4% (95% CI: 38.2-60.5). The use of an expanded diagnostic
      criterion in this study yielded more conservative estimates of the sensitivity of
      VIA and colposcopy.

PMID- 19585572
TI  - Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C
      patients: an analysis based on gender differences.
AB  - Interleukin-6 (IL-6) may play a role in the pathogenesis of hepatocellular
      carcinoma (HCC). Recently, it was reported in mouse models that estrogen-mediated
      inhibition of IL-6 production explains the gender disparity in HCC. We conducted
      a retrospective cohort study to examine whether this hypothesis is applicable to
      human HCC. We enrolled 330 patients with chronic hepatitis C whose serum samples
      were collected between January 1994 and December 2002. Serum IL-6 concentrations
      were measured and patients were divided into three groups according to IL-6
      levels: low, middle, and high. We evaluated the association between serum IL-6
      levels and the risk of subsequent HCC development, including subgroup analysis on
      each gender. During the follow-up period (mean 9.0 yr), HCC developed in 126
      patients. The incidence rates differed significantly among the three groups (p =
      0.015), increasing in accordance with serum IL-6 levels. However, unexpectedly,
      this tendency was significant only in female patients. In a multivariate
      analysis, higher serum IL-6 level was an independent risk factor for HCC
      development in female patients, with a hazard ratio of 1.61. Although female
      patients showed a weak negative correlation between serum IL-6 levels and
      estradiol levels, the lower risk of HCC in female patients cannot be fully
      explained by estrogen-mediated inhibition of IL-6 production. In conclusion,
      higher serum IL-6 level was an independent risk factor for HCC development in
      female but not male chronic hepatitis C patients. Measurement of serum IL-6
      levels may provide useful information for predicting future HCC development in
      female chronic hepatitis C patients.

PMID- 19585574
TI  - Incidence and outcome of acquisition of human papillomavirus infection in women
      with normal cytology--a population-based cohort study from Taiwan.
AB  - Little is known about acquisition of human papillomavirus (HPV) and its outcome
      among older women with negative HPV testing and normal cytology. A longitudinal 3
      yr follow-up of nested-cohort subjects (n = 8825) from a population-based
      cervical cancer screening study whose Pap and HPV tests were negative at baseline
      were conducted. Every active HPV-negative (n = 413) participant had 12-mo follow
      ups of Pap smear and HPV testing. Colposcopy was performed if either HPV-positive
      or cytology was abnormal. The cytology and histology information of the remaining
      subjects (passive HPV-negative, n = 8412) was obtained from national registry
      database. Median age of participants was 45 yr (range, 30-73 yr). The incidence
      of new acquisition was 4.2/100 woman-years. The 3-yr cumulative total HPV
      acquisition rate was 11.1% (95% confidence interval [CI]: 8.1-14.1). Increased
      number of sexual partners (> or =2 vs. 1) of the participant was associated with
      risk of acquisition (odds ratio [OR]: 5.0, 95% CI: 2.0-12.6) by multivariate
      analysis. Three cases of > or = cervical intraepithelial neoplasia (CIN) 2 were
      identified in 3-yr follow-up in active HPV-negative subjects. HPV genotypes in
      the dysplastic tissue were actually present at baseline samples after reanalysis.
      From the passive HPV-negative group, only 1 case progressed to CIN2 probably
      after HPV acquisition. Negative Pap and HPV tests assured a very low risk of
      developing > or = CIN2 within 3 yr despite incident HPV infection.

PMID- 19585575
TI  - GalNAcalpha1-3Gal, a new prognostic marker for cervical cancer.
AB  - Cancer cells undergo significant changes in carbohydrate expression, and these
      alterations can be useful as biomarkers and therapeutic targets. In this study,
      we investigated the expression of carbohydrate antigens containing a terminal
      GalNAcalpha1-3Gal or GalNAcalpha1-6Gal on human cervix and cervical carcinoma.
      Monoclonal antibodies to each of these carbohydrates were generated by immunizing
      rabbits with the corresponding antigen conjugated to KLH followed by hybridoma
      production. Antibodies were screened and evaluated using a combination of
      carbohydrate microarray profiling, ELISA, dot blot and immunohistochemical
      staining to verify specificity. Antibody 132-3 was found to selectively recognize
      GalNAcalpha1-3Gal with little cross-reactivity to other structurally similar
      antigens such as GalNAcalpha1-6Gal, blood group A, Forssman antigen and the Tn
      antigen on both solution assays and human tissue. Although GalNAcalpha1-6Gal
      expression was not detected, GalNAcalpha1-3Gal expression was found on 55% of
      squamous cell carcinomas. Expression in normal tissue was observed but was
      restricted to the suprabasal epithelial layer. Importantly, we found expression
      of the antigen on cervical cancer had a statistically significant correlation
      with the 5-year survival rate of the patients (48 vs. 85% for antigen negative
      vs. positive, p = 0.017). Expression of GalNAcalpha1-3Gal did not correlate with
      other clinical factors including tumor stage, size and lymph node metastasis,
      indicating the antigen is a new, independent biomarker for the prognosis of
      cervical cancer.

PMID- 19585576
TI  - Mortality in a long-term follow-up after treatment of CIN.
AB  - After treatment of the cervical intraepithelial neoplasia (CIN) cervical cancer
      incidence remains elevated at least for 20 years. Whether the overall or cervical
      cancer mortality after treatment of CIN is elevated is unknown. The aim of this
      study was to determine the long-term survival and cause-specific mortality among
      women treated for CIN. The study population consisted of 7,104 women treated for
      CIN between 1974 and 2001 and 35,437 individually matched controls. The follow-up
      of mortality was based on nationwide registries and closed at death, emigration
      or December 31, 2005. The possible differences in mortality were assessed using
      Cox proportional hazard model. With follow-up time of approximately 630,000 woman
      years, overall 2,781 deaths were observed, 530 among women treated for CIN and
      2,251 among reference population (HR 1.1, 95% CI 1.0-1.3). Mortality from any
      cancer (HR 1.4, 95% CI 1.2-1.7), lung cancer (HR 2.7, 95% CI 1.8-4.1) and HPV
      related anogenital cancer (HR 3.1, 95% CI 1.1-8.6) was higher among CIN patients,
      but mortality from cervical cancer was not (HR 1.0, 95% CI 0.3-4.0). Elevated
      cervical cancer incidence after treatment of CIN, documented earlier, did not
      predict elevation in cervical cancer mortality. This suggests high effectiveness
      of CIN management. Most of the excess mortality observed among CIN patients was
      due to increased risk of other cancers. These long-term mortality patterns should
      be considered when planning and evaluating the management of CIN lesions and
      related cervical or other cancer prevention activity.

PMID- 19585577
TI  - The novel tumor-suppressor Mel-18 in prostate cancer: its functional
      polymorphism, expression and clinical significance.
AB  - Mel-18 is a member of the polycomb group (PcG) proteins, which are chromatin
      regulatory factors and play important roles in development and oncogenesis. This
      study was designed to investigate the clinical and prognostic significance of Mel
      18 in patients with prostate cancer. A total of 539 native Japanese subjects
      consisting of 393 prostate cancer patients and 146 controls were enrolled in this
      study. Mel-18 genotyping was analyzed using a PCR-RFLP method and an automated
      sequencer using the GENESCAN software. Immunohistochemistry revealed that Mel-18
      expression was diminished in high grade and high stage prostate cancers.
      Moreover, patients with positive Mel-18 expression had significantly longer PSA
      recurrence-free survival than patients negative for Mel-18 expression (p=0.038).
      A Mel-18 1805A/G SNP was located in the 3' untranslated region and was predicted
      to alter the secondary structure of the mRNA. Mel-18 mRNA expression of the 1805A
      allele was clearly higher than expression of the 1805G allele by allele specific
      quantitative RT-PCR. In multivariate analysis, a homozygous G allele genotype and
      negative Mel-18 expression were independent risk factors predicting high PSA
      recurrence after radical prostatectomy, with HRs of 2.757 (p=0.022) and 2.271
      (p=0.045), respectively. Moreover, the G allele was also an independent predictor
      of poor cancer-specific survival with an HR of 4.658 (p=0.019) for patients with
      stage D2 prostate cancer. This is the first study to provide important evidence
      demonstrating that Mel-18 is a tumor suppressor and possible therapeutic target,
      as well as a diagnostic marker for poor prognosis in prostate cancer patients.

PMID- 19585579
TI  - Expression of microRNA-221 is progressively reduced in aggressive prostate cancer
      and metastasis and predicts clinical recurrence.
AB  - Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of
      a variety of cancers, including prostate carcinoma (PCa). Little information is
      available regarding miR expression levels in lymph node metastasis of prostate
      cancer or the potential of miRs as prognostic markers in this disease. Therefore,
      we analyzed the global expression of miRs in benign, hyperplastic prostate tissue
      (BPH), primary PCa of a high risk group of PCa patients, and corresponding
      metastatic tissues by microarray analysis. Consistent with the proposal that some
      miRs are oncomirs, we found aberrant expression of several miRs, including the
      downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was
      negatively correlated with the expression of the proto-oncogen c-kit in primary
      carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was
      progressively downregulated in aggressive forms of PCa. Downregulation of miR-221
      was associated with clinicopathological parameters, including the Gleason score
      and the clinical recurrence during follow up. Kaplan-Meier estimates and Cox
      proportional hazard models showed that miR-221 downregulation was linked to tumor
      progression and recurrence in a high risk prostate cancer cohort. Our results
      showed that progressive miR-221 downregulation hallmarks metastasis and presents
      a novel prognostic marker in high risk PCa. This suggests that miR-221 has
      potential as a diagnostic marker and therapeutic target in PCa.

PMID- 19585578
TI  - Body size, adult BMI gain and endometrial cancer risk: the multiethnic cohort.
AB  - The effect of body size and change in BMI on endometrial cancer risk across
      different racial/ethnic groups has not been studied. We examined the association
      between body size and endometrial cancer risk and potential effect modification
      of other risk factors among 50,376 women in the Multiethnic Cohort Study. During
      10.3 years of follow-up, 463 endometrial cancer cases were identified.
      Epidemiologic data were collected from the baseline questionnaire. "BMI change"
      was defined as the percentage of body mass index change from age 21 to the time
      of recruitment. Women who were heavier at age 21 or at baseline (weight > or =
      53.5 kg or > or = 63.9 kg, respectively) had an increased endometrial cancer risk
      compared to the lowest quartile of weight during the respective periods. BMI gain
      > or = 35% had a RR of 4.12 (95% CI: 2.69, 6.30) compared to the reference group
      (-5% < or = BMI change <+5%). Women who averaged an annual BMI gain > or = 1% had
      a >3.21-fold (95% CI: 2.37, 4.33) increased risk compared to women who maintained
      a stable adult BMI (-0.25 to <+0.25%). The highest risk associated with BMI gain
      was observed among nulliparous women and postmenopausal women who never used
      hormone therapy. Although African Americans and Whites showed an increase in risk
      after > or =35% BMI gain, Japanese Americans showed an increase in risk with much
      smaller gain (> or =5%). In conclusion, adult obesity and increase in adiposity
      are risk factors for endometrial cancer; and the risk associated with these
      factors may vary across racial/ethnic groups.

PMID- 19585580
TI  - Small interfering RNA-mediated CXCR1 or CXCR2 knock-down inhibits melanoma tumor
      growth and invasion.
AB  - CXCR1 and CXCR2 are receptors for CXCL-8 and are differentially expressed on
      melanoma and endothelial cells. In this study, we determined the functional role
      of these receptors in melanoma progression. We stably knock-down the expression
      of CXCR1 and/or CXCR2 in A375-SM (SM; high metastatic) human melanoma cells by
      short-hairpin RNA transfection. Cell proliferation, migration, invasion, ERK
      phosphorlyation and cytoskeletal rearrangements were carried out in vitro. In
      vivo growth was evaluated using murine subcutaneous xenograft model. Our data
      demonstrate that knock-down of CXCR1 and/or CXCR2 expression, inhibited melanoma
      cell proliferation, survival, migration and invasive potential in vitro.
      Moreover, we also observed inhibition of ERK phosphorylation and cytoskeltal
      rearrangement in SM-shCXCR1, SM-shCXCR2 and SM-shCXCR1/2 cells. Furthermore, when
      SM-shCXCR1 or SM-shCXCR2 cells implanted in nude mice, tumor growth,
      proliferation and microvessel density was significantly inhibited as compared to
      SM-control cells. In addition, we observed a significant increase in melanoma
      cell apoptosis in SM-shCXCR1 and SM-shCXCR2 tumors compared to SM-control tumors.
      Together, these data demonstrate that CXCR1 and CXCR2 expression play a critical
      role in human melanoma tumor progression and, functional blockade of CXCR1 and
      CXCR2 could be potentially used for future therapeutic intervention in malignant
      melanoma.

PMID- 19585581
TI  - Mechanical and cell viability properties of crosslinked low- and high-molecular
      weight poly(ethylene glycol) diacrylate blends.
AB  - There is a strong need for tissue engineering scaffolds that are mechanically
      robust, exhibit good biocompatibility, and can be made from readily available
      materials. To this end, blends of commercially available poly(ethylene glycol)
      diacrylate (PEGDA) with molecular weights of 400 and 3400 were UV-crosslinked at
      total polymer concentrations that varied systematically from 20 to 40 wt %. The
      compressive strength and cell viability were determined for each PEGDA mixture.
      The compressive modulus of the blends was maximized when the weight percent ratio
      PEGDA3400/400 was about 40/60, with the compressive strength reaching 1.7 MPa.
      Cell viability results with a LIVE/DEAD fluorescence assay show an average
      viability of approximately 80% at a total PEGDA concentration of 20 wt % for all
      blends. Increasing the total polymer concentration increased the compressive
      modulus of a polymer, but adversely affected cell viability for all the PEGDA
      blend compositions. The blend composition affected the mechanical behavior of the
      discs, where a higher degree of crosslinking was achieved by increasing the
      concentration of shorter chained PEGDA400, whereas elasticity was gained by
      incorporating longer chained PEGDA3400 into the blends. These results can be
      exploited for use in tissue engineering applications, where a mechanically robust
      scaffold is advantageous.

PMID- 19585582
TI  - Stereoselective synthesis and characterization of new enantiomerically pure
      phosphoric acids.
AB  - Starting from (R)-6,6'-dimethyldiphenyl-2,2'-dicarboxylic acid, a novel class of
      enantiomerically pure cyclic dialkyl phosphates was synthesized and properly
      characterized. The absolute configuration was determined by 2D NOESY experiments.
      The catalytic behavior of the new chiral Bronsted acids was investigated in the
      stereoselective addition of a silyl keteneacetal to aldimines. The Mannich-type
      reaction was promoted in up to 94% yields and enantioselectivities up to 55%. On
      the basis of preliminary molecular mechanic calculations, a model of
      stereoselection was also proposed to explain the sense of the enantioselectivity
      observed in the reaction.

PMID- 19585583
TI  - p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic
      diabetes insipidus is due to a lack of arginine vasopressin-induced
      phosphorylation.
AB  - Vasopressin regulates human water homeostasis by re-distributing homotetrameric
      aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical
      membrane of renal principal cells, a process in which phosphorylation of AQP2 at
      S256 by cAMP-dependent protein kinase A (PKA) is thought to be essential.
      Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is
      unable to concentrate urine in response to vasopressin, is caused by AQP2 gene
      mutations. Here, we investigated a reported patient case of dominant NDI caused
      by a novel p.R254Q mutation. Expressed in oocytes, AQP2-p.R254Q appeared to be a
      functional water channel, but was impaired in its transport to the cell surface
      to the same degree as AQP2-p.S256A, which mimics non-phosphorylated AQP2. In
      polarized MDCK cells, AQP2-p.R254Q was retained and was distributed similarly to
      that of unstimulated wt-AQP2 or AQP2-p.S256A. Upon co-expression, AQP2-p.R254Q
      interacted with, and retained wt-AQP2 in intracellular vesicles. In contrast to
      wild-type AQP2, forskolin did not increase AQP2-p.R254Q phosphorylation at S256
      or its translocation to the apical membrane. Mimicking constitutive
      phosphorylation in AQP2-p.R254Q with the p.S256D mutation, however, rescued its
      apical membrane expression. These date indicate that a lack of S256
      phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a
      loss of function instead of a gain of function mutation in dominant NDI.

PMID- 19585584
TI  - The Neuroscience Peer Review Consortium.

PMID- 19585586
TI  - The SCN1A variant database: a novel research and diagnostic tool.
AB  - The neuronal voltage-gated sodium channel Na(v)1.1 encoded by the SCN1A gene
      plays an important role in the generation and propagation of action potentials in
      the central nervous system. Altered function of this channel due to mutations in
      SCN1A leads to hypersynchronous neuronal discharges resulting in seizures or
      migrainous attaques. A large number of distinct sequence variants in SCN1A are
      associated with diverse epilepsy and migraine syndromes. We developed an online
      and freely available database containing all reported sequence variants in SCN1A
      (http://www.molgen.ua.ac.be/SCN1AMutations/). We verified 623 distinct sequence
      variants, listed them using standard nomenclature for description and classified
      them according to their putative pathogenic nature. We provided links to relevant
      publications and information on the associated phenotype. The database can be
      queried using cDNA or protein position, phenotype, variant type or publication.
      By listing all SCN1A variants in a comprehensive manner, this database will
      facilitate interpretation of newly identified sequence variants and provide
      better insight into the genotype-phenotype relations of the growing number of
      SCN1A mutations.

PMID- 19585587
TI  - Focusing effects of L-dopa in Parkinson's disease.
AB  - Previous fMRI motor studies in Parkinson's disease (PD) have suggested that L
      dopa may "normalize" areas of hypo- and hyperactivity. However, results from
      these studies, which were largely based on analyzing BOLD signal amplitude, have
      been conflicting. Examining only amplitude changes at distinct loci may thus be
      inadequate in fully capturing the activation changes induced by L-dopa. In this
      article, we extended prior analyses on the effects of L-dopa by investigating
      both amplitude and spatial changes of brain activation before and after L-dopa.
      Ten subjects with PD, both on and off medication, and ten healthy, age-matched
      controls performed a visuo-motor tracking task in which they sinusoidally
      squeezed a bulb at 0.25, 0.5, and 0.75 Hz. This task was contrasted with static
      squeezing to generate fMRI activation maps. To investigate the effects of L-dopa,
      we examined the amplitude and spatial variance of the BOLD response within
      anatomically-defined regions of interest (ROIs). L-dopa had significant main
      effects on the amplitude of BOLD signal in bilateral primary motor cortex and
      left SMA. In contrast, L-dopa-mediated spatial changes were apparent in bilateral
      cerebellar hemispheres, M1, SMA, and right prefrontal cortex. Moreover, L-dopa
      appeared to normalize the spatial distribution of ROI activation in PD to that of
      the controls. Specifically, L-dopa had a "focusing" effect on activity-an effect
      more pronounced than the typically-measured fMRI amplitude changes. This
      observation is consistent with modeling studies, which demonstrated that dopamine
      increases the signal-to-noise ratio at the neuronal level with a resultant
      focusing of representations at the macroscopic level.

PMID- 19585585
TI  - High density DNA array analysis reveals distinct genomic profiles in a subset of
      gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) generally harbor activating mutations in
      KIT or platelet-derived growth facter receptor (PDGFRA). Mutations in these
      receptor tyrosine kinases lead to dysregulation of downstream signaling pathways
      that contribute to GIST pathogenesis. GISTs with KIT or PDGFRA mutations also
      undergo secondary cytogenetic alterations that may indicate the involvement of
      additional genes important in tumor progression. Approximately 10-15% of adult
      and 85% of pediatric GISTs do not have mutations in KIT or in PDGFRA. Most mutant
      adult GISTs display large-scale genomic alterations, but little is known about
      the mutation-negative tumors. Using genome-wide DNA arrays, we investigated
      genomic imbalances in a set of 31 GISTs, including 10 KIT/PDGFRA mutation
      negative tumors from nine adults and one pediatric case and 21 mutant tumors.
      Although all 21 mutant GISTs exhibited multiple copy number aberrations, notably
      losses, eight of the 10 KIT/PDGFRA mutation-negative GISTs exhibited few or no
      genomic alterations. One KIT/PDGFRA mutation-negative tumor exhibiting numerous
      genomic changes was found to harbor an alternate activating mutation, in the
      serine-threonine kinase BRAF. The only other mutation-negative GIST with
      significant chromosomal imbalances was a recurrent metastatic tumor found to
      harbor a homozygous deletion in chromosome arm 9p. Similar findings in several
      KIT-mutant GISTs identified a minimal overlapping region of deletion of
      approximately 0.28 Mbp in 9p21.3 that includes only the CDKN2A/2B genes, which
      encode inhibitors of cell-cycle kinases. These results suggest that GISTs without
      activating kinase mutations, whether pediatric or adult, generally exhibit a much
      lower level of cytogenetic progression than that observed in mutant GISTs.

PMID- 19585588
TI  - Neural representation of anxiety and personality during exposure to anxiety
      provoking and neutral scenes from scary movies.
AB  - Some people search for intense sensations such as being scared by frightening
      movies while others do not. The brain mechanisms underlying such inter-individual
      differences are not clear. Testing theoretical models, we investigated neural
      correlates of anxiety and the personality trait sensation seeking in 40 subjects
      who watched threatening and neutral scenes from scary movies during functional
      magnetic resonance imaging. Threat versus neutral scenes induced increased
      activation in anterior cingulate cortex, insula, thalamus, and visual areas.
      Movie-induced anxiety correlated positively with activation in dorsomedial
      prefrontal cortex, indicating a role for this area in the subjective experience
      of being scared. Sensation seeking-scores correlated positively with brain
      activation to threat versus neutral scenes in visual areas and in thalamus and
      anterior insula, i.e. regions involved in the induction and representation of
      arousal states. For the insula and thalamus, these outcomes were partly due to an
      inverse relation between sensation seeking scores and brain activation during
      neutral film clips. These results support models predicting cerebral
      hypoactivation in high sensation seekers during neutral stimulation, which may be
      compensated by more intense sensations such as watching scary movies.

PMID- 19585590
TI  - Tuning-in to the beat: Aesthetic appreciation of musical rhythms correlates with
      a premotor activity boost.
AB  - Listening to music can induce us to tune in to its beat. Previous neuroimaging
      studies have shown that the motor system becomes involved in perceptual rhythm
      and timing tasks in general, as well as during preference-related responses to
      music. However, the role of preferred rhythm and, in particular, of preferred
      beat frequency (tempo) in driving activity in the motor system remains unknown.
      The goals of the present functional magnetic resonance imaging (fMRI) study were
      to determine whether the musical rhythms that are subjectively judged as
      beautiful boost activity in motor-related areas and if so, whether this effect is
      driven by preferred tempo, the underlying pulse people tune in to. On the basis
      of the subjects' judgments, individual preferences were determined for the
      different systematically varied constituents of the musical rhythms. Results
      demonstrate the involvement of premotor and cerebellar areas during preferred
      compared to not preferred musical rhythms and indicate that activity in the
      ventral premotor cortex (PMv) is enhanced by preferred tempo. Our findings
      support the assumption that the premotor activity increase during preferred tempo
      is the result of enhanced sensorimotor simulation of the beat frequency. This may
      serve as a mechanism that facilitates the tuning-in to the beat of appealing
      music.

PMID- 19585591
TI  - Kinetic strategies of patients with shoulder impingement syndrome.
AB  - Our aim was to determine whether subjects with shoulder impingement syndrome
      (SIS) have abnormal multijoint torque patterns compared to healthy subjects
      during normalized isometric force along specific directions. Subjects had to
      generate an isometric force corresponding to 40% of the maximal pain-free force.
      Eight targets were displayed on a monitor (0, 45, 90, 135, 180, 225, 270, and 315
      degrees ). We calculated shoulder and elbow torques (kinetic strategies) using a
      biomechanical model. Regardless of the target location, the SIS group succeeded
      in reaching the target; however, when compared to the healthy subjects, they
      needed more time to do so, suggesting that SIS may slow down the execution of the
      kinetic strategies. Moreover, the SIS group produced lower shoulder
      external/internal torque to reach the targets located at 0 degrees and 225
      degrees, and they generated greater abduction/adduction torque for targets
      located at 0, 135, and 180 degrees. In addition, they had lower elbow
      extension/flexion torque for the target located at 315 degrees. The investigation
      of atypical kinetic strategies is essential to provide an understanding of the
      pathomechanics of the SIS and to develop more effective treatment strategies.

PMID- 19585589
TI  - Improving fMRI sensitivity by normalization of basal physiologic state.
AB  - The power of fMRI in assessing neural activities is hampered by inter-subject
      variations in basal physiologic parameters, which may not be related to neural
      activation but has a modulatory effect on fMRI signals. Therefore, normalization
      of fMRI signals with these parameters is useful in reducing variations and
      improving sensitivity of this important technique. Recently, we have shown that
      basal venous oxygenation is a significant modulator of fMRI signals and
      individuals with higher venous oxygenation tend to have lower fMRI signals. In
      this study, we aim to test the utility of venous oxygenation normalization in
      distinguishing subject groups. A "model" condition was used in which two visual
      stimuli with different flashing frequencies were used to stimulate two subject
      groups, respectively, thereby simulating the situation of control and patient
      groups. It was found that visual-evoked BOLD signal is significantly correlated
      with baseline venous T2 (P = 0.0003) and inclusion of physiologic modulator in
      the regression analysis can substantially reduce P values of group-level
      statistical tests. When applied to voxel-wise analysis, the normalization process
      can allow the detection of more significant voxels. The utility of other basal
      parameters, including blood pressure, heart rate, arterial oxygenation, and end
      tidal CO(2), in BOLD normalization was also assessed and it was found that the
      improvement was less significant. Time-to-peak of the BOLD responses was also
      studied and it was found that subjects with higher basal venous oxygenation tend
      to slower BOLD responses.

PMID- 19585592
TI  - Effect of exogenous IGF-1 on chondrocyte apoptosis in a rabbit intraarticular
      osteotomy model.
AB  - Insulin-like growth factor-1 (IGF-1) has been shown to protect chondrocytes from
      apoptosis in vitro. IGF-1 expression may also assist in maintaining a fully
      differentiated chondrocyte phenotype. Theoretically, posttraumatic administration
      of IGF-1 may inhibit chondrocyte apoptosis. This study is to determine if
      administration of IGF-1 after fracture inhibits apoptosis in vivo. Twenty-four
      mature female New Zealand white rabbits were randomized to control and IGF-1
      groups. All subjects underwent standardized medial femoral condyle fracture and
      repair. Fibrin clot was administered in all subjects, with 25 mcg/ml IGF-1 in the
      clot in half the subjects. Half of the animals in each group were sacrificed at 2
      weeks and half at 4 weeks, specimens were fixed and underwent TUNEL staining. Two
      week controls showed significantly higher rate of apoptosis than 2-week IGF-1
      subjects (21 +/- 6 vs. 12 +/- 6, p = 0.04). Likewise, 4-week controls showed
      significantly higher rate of apoptosis than 2-week IGF-1 subjects (23 +/- 7 vs.
      10 +/- 2, p = 0.01). There was no significant administration difference between 2
      week control and 4-week control subjects, or between 2-week IGF-1 and 4-week IGF
      1 subjects. Intraarticular IGF-1 at the time of fracture repair appears to
      inhibit chondrocyte apoptosis in vivo, as judged by TUNEL staining, in this
      animal model. If administration of IGF-1 inhibits human chondrocyte apoptosis in
      vivo, this may lead to interventions that may reduce posttraumatic arthritis
      after fracture.

PMID- 19585594
TI  - Accelerated cardiac perfusion imaging using k-t SENSE with SENSE training.
AB  - In k-t sensitivity encoding (SENSE), MR data acquisition performed in parallel by
      multiple coils is accelerated by sparsely sampling the k-space over time. The
      resulting aliasing is resolved by exploiting spatiotemporal correlations inherent
      in dynamic images of natural objects. In this article, a modified k-t SENSE
      reconstruction approach is presented, which aims at improving the temporal
      fidelity of first-pass, contrast-enhanced myocardial perfusion images at high
      accelerations. The proposed technique is based on applying parallel imaging on
      the training data in order to increase their spatial resolution. At a net
      acceleration of 5.8 (k-t factor = 8, training profiles = 11) accurate
      representations of dynamic signal-intensities were achieved. The efficacy of this
      approach as well as limitations due to noise amplification were investigated in
      computer simulations and in vivo experiments.

PMID- 19585593
TI  - In vivo cytometry of antigen-specific t cells using 19F MRI.
AB  - Noninvasive methods to image the trafficking of phenotypically defined immune
      cells are paramount as we attempt to understand adaptive immunity. A (19)F MRI
      based methodology for tracking and quantifying cells of a defined phenotype is
      presented. These methods were applied to a murine inflammation model using
      antigen-specific T cells. The T cells that were intracellularly labeled ex vivo
      with a perfluoropolyether (PFPE) nanoemulsion and cells were transferred to a
      host receiving a localized inoculation of antigen. Longitudinal (19)F MRI over 21
      days revealed a dynamic accumulation and clearance of T cells in the lymph node
      (LN) draining the antigen. The apparent T-cell numbers were calculated in the LN
      from the time-lapse (19)F MRI data. The effect of in vivo T-cell division on the
      (19)F MRI cell quantification accuracy was investigated using fluorescence
      assays. Overall, in vivo cytometry using PFPE labeling and (19)F MRI is broadly
      applicable to studies of whole-body cell biodistribution.

PMID- 19585595
TI  - Elliptical field-of-view PROPELLER imaging.
AB  - Traditionally two-dimensional scans are designed to support an isotropic field-of
      view (iFOV). When imaging elongated objects, significant savings in scan time can
      potentially be achieved by supporting an elliptical field-of-view (eFOV). This
      work presents an empirical closed-form solution to adapt the PROPELLER trajectory
      for an eFOV. The proposed solution is built on the geometry of the PROPELLER
      trajectory permitting the scan prescription and data reconstruction to remain
      largely similar to standard PROPELLER. The achieved FOV is experimentally
      validated by the point spread function (PSF) of a phantom scan. The details of
      potential savings in scan time and the signal-to-noise ratio (SNR) performance in
      comparison to iFOV scans for both phantom and in-vivo images are also described.

PMID- 19585596
TI  - TREMR: Table-resonance elastography with MR.
AB  - Magnetic resonance elastography (MRE) is a noninvasive method of measuring tissue
      compliance. Current MRE methods rely on custom-built hardware to elicit
      vibrations that are tracked by MR imaging. Knowledge of the wave propagation can
      be used to calculate the local shear stiffness of the tissue. We sought to
      determine whether the vibrations of the patient table that result from low
      frequency switching of the imaging gradients could be used as an alternative
      mechanical driving mechanism for MRE. We designed a pulse sequence that includes
      a gradient lobe specifically for the excitation of mechanical resonance, allowing
      control of the time between the onset of the vibrations and the velocity-encoding
      of the readout. Data collected from a gelatin phantom with stiff cylindrical
      gelatin inserts demonstrated that wave propagation can be imaged with this
      method. Postprocessing to estimate the local spatial frequency of the waves also
      allows estimation of the local shear stiffness, where the stiff inserts are
      clearly identifiable. Data collected on the brain of a normal healthy volunteer
      showed clear rotational waves propagating from the skull inwards, also allowing
      generation of shear stiffness maps.

PMID- 19585597
TI  - Non-contrast-enhanced perfusion and ventilation assessment of the human lung by
      means of fourier decomposition in proton MRI.
AB  - Assessment of regional lung perfusion and ventilation has significant clinical
      value for the diagnosis and follow-up of pulmonary diseases. In this work a new
      method of non-contrast-enhanced functional lung MRI (not dependent on intravenous
      or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast
      imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms,
      acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR
      scanner. The imaging protocol comprised sets of 198 lung images acquired with an
      imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram
      (ECG) or respiratory triggering was used. A nonrigid image registration algorithm
      was applied to compensate for respiratory motion. Rapid data acquisition allowed
      observing intensity changes in corresponding lung areas with respect to the
      cardiac and respiratory frequencies. After a Fourier analysis along the time
      domain, two spectral lines corresponding to both frequencies were used to
      calculate the perfusion- and ventilation-weighted images. The described method
      was applied in preliminary studies on volunteers and patients showing clinical
      relevance to obtain non-contrast-enhanced perfusion and ventilation data.

PMID- 19585598
TI  - High dynamic-range magnetic resonance spectroscopy (MRS) time-domain signal
      analysis.
AB  - In the absence of water signal suppression, the proton magnetic resonance
      spectroscopy ((1)H MRS) in vivo water resonance signal-to-noise ratio (SNR) is
      orders of magnitude larger than the SNR of all the other resonances. In this
      case, because the high-SNR water resonance dominates the data, it is difficult to
      obtain reliable parameter estimates for the low SNR resonances. Herein, a new
      model is described that offers a solution to this problem. In this model, the
      time-domain signal for the low SNR resonances is represented as the conventional
      sum of exponentially decaying complex sinusoids. However, the time-domain signal
      for the high SNR water resonance is assumed to be a complex sinusoid whose
      amplitude is slowly varying from pure exponential decay and whose phase is slowly
      varying from a constant frequency. Thus, the water resonance has only an
      instantaneous amplitude and frequency. The water signal is neither filtered nor
      subtracted from the data. Instead, Bayesian probability theory is used to
      simultaneously estimate the frequencies, decay-rate constants, and amplitudes for
      all the low SNR resonances, along with the water resonance's time-dependent
      amplitude and phase. While computationally intensive, this approach models all of
      the resonances, including the water and the metabolites of interest, to within
      the noise level.

PMID- 19585599
TI  - Bolus-tracking MRI with a simultaneous T1- and T2*-measurement.
AB  - The aim of this study was to propose and evaluate a methodology to analyze
      simultaneously acquired T2*-weighted dynamic susceptibility contrast (DSC) MRI
      and T(1)-weighted dynamic contrast enhanced (DCE) MRI data. Two generalized
      models of T2*-relaxation are proposed to account for tracer leakage, and a two
      compartment exchange model is used to separate tracer in intra- and extravascular
      spaces. The methods are evaluated using data extracted from ROIs in three mice
      with subcutaneously implanted human colorectal tumors. Comparing plasma flow
      values obtained from DCE-MRI and DSC-MRI data defines a practical experimental
      paradigm to measure T2*-relaxivities, and reveals a factor of 15 between values
      in tissue and blood. Comparing mean transit time values obtained from DCE-MRI and
      DSC-MRI without leakage correction, indicates a significant reduction of
      susceptibility weighting in DSC-MRI during tracer leakage. A one-parameter
      gradient correction model provides a good approximation for this susceptibility
      loss, but redundancy of the parameter limits the practical potential of this
      model for DSC-MRI. Susceptibility loss is modeled more accurately with a variable
      T2*-relaxivity, which allows to extract new parameters that cannot be derived
      from DSC-MRI or DCE-MRI alone. They reflect the cellular and vessel geometry, and
      thus may lead to a more complete characterization of tissue structure.

PMID- 19585600
TI  - Reduction of B1 sensitivity in selective single-slab 3D turbo spin echo imaging
      with very long echo trains.
AB  - Single-slab 3D turbo/fast spin echo (SE) imaging with very long echo trains was
      recently introduced with slab selection using a highly selective excitation pulse
      and short, nonselective refocusing pulses with variable flip angles for high
      imaging efficiency. This technique, however, is vulnerable to image degradation
      in the presence of spatially varying B(1) amplitudes. In this work we develop a
      B(1) inhomogeneity-reduced version of single-slab 3D turbo/fast SE imaging based
      on the hypothesis that it is critical to achieve spatially uniform excitation.
      Slab selection was performed using composite adiabatic selective excitation
      wherein magnetization is tipped into the transverse plane by a nonselective
      adiabatic-half-passage pulse and then slab is selected by a pair of selective
      adiabatic-full-passage pulses. Simulations and experiments were performed to
      evaluate the proposed technique and demonstrated that this approach is a simple
      and efficient way to reduce B(1) sensitivity in single-slab 3D turbo/fast SE
      imaging with very long echo trains.

PMID- 19585601
TI  - Evaluation of a positron emission tomography (PET)-compatible field-cycled MRI
      (FCMRI) scanner.
AB  - Field-cycled MRI (FCMRI) uses two independent, actively controlled resistive
      magnets to polarize a sample and to provide the magnetic field environment during
      data acquisition. This separation of tasks allows for novel forms of contrast,
      reduction of susceptibility artifacts, and a versatility in design that
      facilitates the integration of a second imaging modality. A 0.3T/4-MHz FCMRI
      scanner was constructed with a 9-cm-wide opening through the side for the
      inclusion of a photomultiplier-tube-based positron emission tomography (PET)
      system. The performance of the FCMRI scanner was evaluated prior to integrating
      PET detectors. Quantitative measurements of the system's signal, phase, and
      temperature were recorded. The polarizing and readout magnets could be operated
      continuously at 100 A without risk of damage to the system. Transient
      instabilities in the readout magnet, caused by the pulsing of the polarizing
      magnet, dissipated in 50 ms; this resulted in a steady-state homogeneity of 32 Hz
      over a 7-cm-diameter volume. The short- and long-term phase behaviors of the
      readout field were sufficiently stable to prevent visible readout or phase-encode
      artifacts during imaging. Preliminary MR images demonstrated the potential of the
      FCMRI scanner and the efficacy of integrating a PET system.

PMID- 19585602
TI  - Towards automatic patient positioning and scan planning using continuously moving
      table MR imaging.
AB  - A concept is proposed to simplify patient positioning and scan planning to
      improve ease of use and workflow in MR. After patient preparation in front of the
      scanner the operator selects the anatomy of interest by a single push-button
      action. Subsequently, the patient table is moved automatically into the scanner,
      while real-time 3D isotropic low-resolution continuously moving table scout
      scanning is performed using patient-independent MR system settings. With a real
      time organ identification process running in parallel and steering the scanner,
      the target anatomy can be positioned fully automatically in the scanner's
      sensitive volume. The desired diagnostic examination of the anatomy of interest
      can be planned and continued immediately using the geometric information derived
      from the acquired 3D data. The concept was implemented and successfully tested in
      vivo in 12 healthy volunteers, focusing on the liver as the target anatomy. The
      positioning accuracy achieved was on the order of several millimeters, which
      turned out to be sufficient for initial planning purposes. Furthermore, the
      impact of nonoptimal system settings on the positioning performance, the signal
      to-noise ratio (SNR), and contrast-to-noise ratio (CNR) was investigated. The
      present work proved the basic concept of the proposed approach as an element of
      future scan automation.

PMID- 19585603
TI  - k-t PCA: temporally constrained k-t BLAST reconstruction using principal
      component analysis.
AB  - The k-t broad-use linear acquisition speed-up technique (BLAST) has become
      widespread for reducing image acquisition time in dynamic MRI. In its basic form
      k-t BLAST speeds up the data acquisition by undersampling k-space over time
      (referred to as k-t space). The resulting aliasing is resolved in the Fourier
      reciprocal x-f space (x = spatial position, f = temporal frequency) using an
      adaptive filter derived from a low-resolution estimate of the signal covariance.
      However, this filtering process tends to increase the reconstruction error or
      lower the achievable acceleration factor. This is problematic in applications
      exhibiting a broad range of temporal frequencies such as free-breathing
      myocardial perfusion imaging. We show that temporal basis functions calculated by
      subjecting the training data to principal component analysis (PCA) can be used to
      constrain the reconstruction such that the temporal resolution is improved. The
      presented method is called k-t PCA.

PMID- 19585604
TI  - Have the primary structures of biomacromolecules been selected in a Darwinian
      fashion to adapt to the surrounding environments of our planet?

PMID- 19585605
TI  - Automatic slice positioning (ASP) for passive real-time tracking of
      interventional devices using projection-reconstruction imaging with echo
      dephasing (PRIDE).
AB  - A novel and fast approach for passive real-time tracking of interventional
      devices using paramagnetic markers, termed "projection-reconstruction imaging
      with echo-dephasing" (PRIDE) is presented. PRIDE is based on the acquisition of
      echo-dephased projections along all three physical axes. Dephasing is preferably
      set to 4pi within each projection ensuring that background tissues do not
      contribute to signal formation and thus appear heavily suppressed. However,
      within the close vicinity of the paramagnetic marker, local gradient fields
      compensate for the intrinsic dephasing to form an echo. Successful localization
      of the paramagnetic marker with PRIDE is demonstrated in vitro and in vivo in the
      presence of different types of off-resonance (air/tissue interfaces, main
      magnetic field inhomogeneities, etc). In order to utilize the PRIDE sequence for
      vascular interventional applications, it was interleaved with balanced steady
      state free precession (bSSFP) to provide positional updates to the imaged slice
      using a dedicated real-time feedback link. Active slice positioning (ASP) with
      PRIDE is demonstrated in vitro, requiring approximately 20 ms for the positional
      update to the imaging sequence, comparable to existing active tracking methods.

PMID- 19585606
TI  - Time-resolved three-dimensional (3D) phase-contrast (PC) balanced steady-state
      free precession (bSSFP).
AB  - In this study the feasibility of a time-resolved, three-dimensional (3D), three
      directional flow-sensitive balanced steady-state free precession (bSSFP) sequence
      is demonstrated. Due to its high signal-to-noise ratio (SNR) in blood and
      cerebrospinal fluid (CSF) this type of sequence is particularly effective for
      acquisition of blood and CSF flow velocities. Flow sensitivity was achieved with
      the phase-contrast (PC) technique, implementing a custom algorithm for
      calculation of optimal gradient parameters. Techniques to avoid the most
      important sources of bSSFP-related artifacts (including distortion due to eddy
      currents and signal voids due to flow-related steady-state disruption) are also
      presented. The technique was validated by means of a custom flow phantom, and in
      vivo experiments on blood and CSF were performed to demonstrate the suitability
      of this sequence for human studies. Accurate depiction of blood flow in the
      cerebral veins and of CSF flow in the cervical portion of the neck was obtained.
      Possible applications of this technique might include the study of CSF flow
      patterns, direct in vivo study of pathologies such as hydrocephalus and Chiari
      malformation, and validation for the existing CSF circulation model.

PMID- 19585607
TI  - Application of subsecond spiral chemical shift imaging to real-time multislice
      metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1
      pyruvate.
AB  - Dynamic nuclear polarization can create hyperpolarized compounds with MR signal
      to-noise ratio enhancements on the order of 10,000-fold. Both exogenous and
      normally occurring endogenous compounds can be polarized, and their initial
      concentration and downstream metabolic products can be assessed using MR
      spectroscopy. Given the transient nature of the hyperpolarized signal
      enhancement, fast imaging techniques are a critical requirement for real-time
      metabolic imaging. We report on the development of an ultrafast, multislice,
      spiral chemical shift imaging sequence, with subsecond acquisition time, achieved
      on a clinical MR scanner. The technique was used for dynamic metabolic imaging in
      rats, with measurement of time-resolved spatial distributions of hyperpolarized
      (13)C(1)-pyruvate and metabolic products (13)C(1)-lactate and (13)C(1)-alanine,
      with a temporal resolution of as fast as 1 s. Metabolic imaging revealed
      different signal time courses in liver from kidney. These results demonstrate the
      feasibility of real-time, hyperpolarized metabolic imaging and highlight its
      potential in assessing organ-specific kinetic parameters.

PMID- 19585608
TI  - General formulation for quantitative G-factor calculation in GRAPPA
      reconstructions.
AB  - In this work a theoretical description for practical quantitative estimation of
      the noise enhancement in generalized autocalibrating partially parallel
      acquisitions (GRAPPA) reconstructions, equivalent to the geometry (g)-factor in
      sensitivity encoding for fast MRI (SENSE) reconstructions, is described. The
      GRAPPA g-factor is derived directly from the GRAPPA reconstruction weights. The
      procedure presented here also allows the calculation of quantitative g-factor
      maps for both the uncombined and combined accelerated GRAPPA images. This
      enables, for example, a fast comparison between the performances of various
      GRAPPA reconstruction kernels or SENSE reconstructions. The applicability of this
      approach is validated on phantom studies and demonstrated using in vivo images
      for 1D and 2D parallel imaging.

PMID- 19585609
TI  - Numerical and in vivo validation of fast cine displacement-encoded with
      stimulated echoes (DENSE) MRI for quantification of regional cardiac function.
AB  - Quantitative assessment of regional cardiac function can improve the accuracy of
      detecting wall motion abnormalities due to heart disease. While recently
      developed fast cine displacement-encoded with stimulated echoes (DENSE) MRI is a
      promising modality for the quantification of regional myocardial function, it has
      not been validated for clinical applications. The purpose of this study,
      therefore, was to validate the accuracy of fast cine DENSE MRI with numerical
      simulation and in vivo experiments. A numerical phantom was generated to model
      physiologically relevant deformation of the heart, and the accuracy of fast cine
      DENSE was evaluated against the numerical reference. For in vivo validation, 12
      controls and 13 heart-disease patients were imaged using both fast cine DENSE and
      myocardial tagged MRI. Numerical simulation demonstrated that the echo
      combination DENSE reconstruction method is relatively insensitive to clinically
      relevant resonance frequency offsets. The strain measurements by fast cine DENSE
      and the numerical reference were strongly correlated and in excellent agreement
      (mean difference = 0.00; 95% limits of agreement were 0.01 and -0.02). The strain
      measurements by fast cine DENSE and myocardial tagged MRI were strongly
      correlated (correlation coefficient = 0.92) and in good agreement (mean
      difference = 0.01; 95% limits of agreement were 0.07 and -0.04).

PMID- 19585611
TI  - The role of the hepatocyte cytokeratin network in bile formation and resistance
      to bile acid challenge and cholestasis in mice.
AB  - The intermediate filament cytoskeleton of hepatocytes is composed of keratin (K)
      8 and K18 and has important mechanical and nonmechanical functions. However, the
      potential role of the K8/K18 network for proper membrane targeting of
      hepatocellular adenosine triphosphate-binding cassette transporters and bile
      formation is unknown. We therefore designed a comparative study in K8 and K18
      knockout mice and respective wild-type controls to test the hypothesis that
      intermediate filaments of hepatocytes play a role in normal bile formation. In
      addition, we challenged mice either with a 1% cholic acid-supplemented diet or a
      diet containing the porphyrinogenic xenobiotic 3,5-diethoxycarbonyl-1,4
      dihydrocollidine to determine the effect of K8/K18 loss on bile flow/composition
      and liver injury under different physiological and toxic stress stimuli. Protein
      expression levels and membrane localization of various transporters and anion
      exchangers were compared using western blotting and immunofluorescence
      microscopy, respectively, and bile flow and composition were determined under
      various experimental conditions. Our results demonstrate that loss of the
      intermediate filament network had no significant effect on bile formation and
      composition, as well as expression levels and membrane targeting of key
      hepatobiliary transporters under baseline and stress conditions. However, loss of
      K8 significantly increased liver injury in response to toxic stress. CONCLUSION:
      The intermediate filament network of hepatocytes is not specifically required for
      proper bile formation in mice.

PMID- 19585610
TI  - Keratin variants are overrepresented in primary biliary cirrhosis and associate
      with disease severity.
AB  - Keratins (K) 8 and 18 variants predispose carriers to the development of end
      stage liver disease and patients with chronic hepatitis C to disease progression.
      Hepatocytes express K8/K18, whereas biliary epithelia express K8/K18/K19. K8-null
      mice, which are predisposed to liver injury, spontaneously develop anti
      mitochondrial antibodies (AMA) and have altered hepatocyte mitochondrial size and
      function. There is no known association of K19 with human disease and no known
      association of K8/K18/K19 with human autoimmune liver disease. We tested the
      hypothesis that K8/K18/K19 variants associate with primary biliary cirrhosis
      (PBC), an autoimmune cholestatic liver disease characterized by the presence of
      serum AMA. In doing so, we analyzed the entire exonic regions of K8/K18/K19 in
      201 Italian patients and 200 control blood bank donors. Five disease-associated
      keratin heterozygous variants were identified in patients versus controls (K8
      G62C/R341H/V380I, K18 R411H, and K19 G17S). Four variants were novel and included
      K19 G17S/V229M/N184N and K18 R411H. Overall, heterozygous disease-associated
      keratin variants were found in 17 of 201 (8.5%) PBC patients and 4 of 200 (2%)
      blood bank donors (P < 0.004, odds ratio = 4.53, 95% confidence interval = 1.5
      13.7). Of the K19 variants, K19 G17S was found in three patients but not in
      controls and all K8 R341H (eight patients and three controls) associated with
      concurrent presence of the previously described intronic K8 IVS7+10delC deletion.
      Notably, keratin variants associated with disease severity (12.4% variants in
      Ludwig stage III/IV versus 4.2% in stages I/II; P < 0.04, odds ratio = 3.25, 95%
      confidence interval = 1.02-10.40), but not with the presence of AMA. CONCLUSION:
      K8/K18/K19 variants are overrepresented in Italian PBC patients and associate
      with liver disease progression. Therefore, we hypothesize that K8/K18/K19
      variants may serve as genetic modifiers in PBC.

PMID- 19585612
TI  - Porcine liver sinusoidal endothelial cells contribute significantly to
      intrahepatic ammonia metabolism.
AB  - Ammonia metabolism in the liver has been largely credited to hepatocytes (HCs).
      We have shown that liver nonparenchymal cells that include liver sinusoidal
      endothelial cells (LSECs) produce ammonia. To address the limited knowledge
      regarding a role for LSECs in ammonia metabolism, we investigated the ammonia
      metabolism of isolated LSECs and HCs under three different conditions: (1)
      bioreactors containing LSECs (LSEC-bioreactors), (2) bioreactors containing HCs
      (HC-bioreactors), and (3) separate bioreactors containing LSECs and HCs connected
      in sequence (Seq-bioreactors). Our results showed that LSEC-bioreactors released
      six-fold more ammonia (22.2 nM/hour/10(6) cells) into the growth media than HC
      bioreactors (3.3 nM/hour/10(6) cells) and Seq-bioreactors (3.8 nM/hour/10(6)
      cells). The glutamate released by LSEC-bioreactors (32.0 nM/hour/10(6) cells) was
      over four-fold larger than that released by HC-bioreactors and Seq-bioreactors
      (<7 nM/hour/10(6) cells). LSEC-bioreactors and HC-bioreactors consumed large
      amounts of glutamine (>25 nM/hour/10(6) cells). Glutaminase is known for
      catalyzing glutamine into glutamate and ammonia. To determine if this mechanism
      may be responsible for the large levels of glutamate and ammonia found in LSEC
      bioreactors, immunolabeling of glutaminase and messenger RNA expression were
      tested. Our results demonstrated that glutaminase was present with colocalization
      of an LSEC-specific functional probe in lysosomes of LSECs. Furthermore, using a
      nucleotide sequence specific for kidney-type glutaminase, reverse-transcription
      polymerase chain reaction revealed that this isoform of glutaminase was expressed
      in porcine LSECs. CONCLUSION: LSECs released large amounts of ammonia, perhaps
      due to the presence of glutaminase in lysosomes. The ammonia and glutamate
      released by LSECs in Seq-bioreactors were used by hepatocytes, suggesting an
      intrahepatic collaboration between these two cell types.

PMID- 19585613
TI  - Human serum albumin: not just a plasma volume expander.

PMID- 19585614
TI  - Increased rate of death related to presence of viremia among hepatitis C virus
      antibody-positive subjects in a community-based cohort study.
AB  - The overall mortality of patients infected with hepatitis C virus (HCV) has not
      been fully elucidated. This study analyzed mortality in subjects positive for
      antibody to HCV (anti-HCV) in a community-based, prospective cohort study
      conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning
      in 1995, 1125 anti-HCV-seropositive residents of Town C were enrolled into the
      study and were followed for mortality through 2005. Cause of death was assessed
      by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV
      RNA were considered as having hepatitis C viremia and were classified as HCV
      carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia
      negative) were considered as having had a prior HCV infection and were classified
      as HCV noncarriers. Among the anti-HCV-positive subjects included in the
      analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231
      deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths
      in the HCV carrier group and 55 in the noncarrier group. The overall mortality
      rate was higher in HCV carriers than in noncarriers, adjusted for age and sex
      (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related
      deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95%
      confidence interval, 2.58-13.7), the rates of other causes of death did not
      differ between HCV carriers and noncarriers. Among HCV carriers, a higher level
      of HCVcAg (>or=100 pg/mL) and persistently elevated alanine aminotransferase
      levels were important predictors of liver-related mortality. CONCLUSION: The
      presence of viremia increases the rate of mortality, primarily due to liver
      related death, among anti-HCV-seropositive persons in Japan.

PMID- 19585615
TI  - Microenvironmental regulation of the sinusoidal endothelial cell phenotype in
      vitro.
AB  - Liver sinusoidal endothelial cells (LSECs) differ, both structurally and
      functionally, from endothelial cells (ECs) lining blood vessels of other tissues.
      For example, in contrast to other ECs, LSECs possess fenestrations, have low
      detectable levels of platelet endothelial cell adhesion molecule 1 expression,
      and in rat tissue, they distinctively express a cell surface marker recognized by
      the SE-1 antibody. These unique phenotypic characteristics seen in hepatic tissue
      are lost over time upon culture in vitro; therefore, this study sought to
      systematically examine the effects of microenvironmental stimuli--namely,
      extracellular matrix and neighboring cells, on the LSEC phenotype in vitro. In
      probing the role of the underlying extracellular matrix, we identified collagen I
      and collagen III as well as mixtures of collagen I/collagen IV/fibronectin as
      having a positive effect on LSEC survival. Furthermore, using a stable
      hepatocellular model (hepatocyte-fibroblast) we were able to prolong the
      expression of both SE-1 and phenotypic functions of LSEC such as factor VIII
      activity and AcLOL uptake in cocultured LSECs through the production of short
      range paracrine signals. In the course of these experiments, we identified the
      antigen recognized by SE-1 as CD32b. CONCLUSION: Collectively, this study has
      identified several microenvironmental regulators of liver sinusoidal endothelial
      cells that prolong their phenotypic functions for up to 2 weeks in culture,
      enabling the development of better in vitro models of liver physiology and
      disease.

PMID- 19585616
TI  - Potential impact of long-term nucleoside therapy on the mortality and morbidity
      of active chronic hepatitis B.
AB  - The potential impact of long-term antiviral therapy on the burden of chronic
      hepatitis B has hardly been documented. The aim of this study was to estimate the
      effects of prolonged antiviral therapy and antiviral resistance on the mortality
      and morbidity of active chronic hepatitis B patients. A population cohort of
      chronic hepatitis B patients in the Netherlands was constructed and stratified
      according to 10-year age groups, prevalence of hepatitis B surface antigen,
      hepatitis B virus DNA level, alanine aminotransferase level, hepatitis B e
      antigen status, and presence of cirrhosis. A Markov model was created to
      mathematically simulate the cohort's progression through a finite series of
      health states. The analysis was performed on the basis of four scenarios: natural
      history, long-term therapy with a high-resistance profile drug without or with
      salvage, and therapy with a low-resistance profile drug. It has been estimated
      that there were 64,000 people (0.4%) suffering from chronic hepatitis B infection
      in the Netherlands in 2005, with 6521 (10%) of them having high viremia and
      elevated alanine aminotransferase levels. Within a 20-year period, 1725 (26%) of
      the 6521 patients in the active chronic hepatitis B cohort will die because of
      liver-related causes. Of the 5685 without cirrhosis at entry, 1671 (29%) will
      develop cirrhosis. Of those 836 with cirrhosis at entry, 619 (74%) will die
      within a 20-year period. If this active chronic hepatitis B cohort is fully
      detected and treated, mortality related to liver disease can be reduced by 80% if
      a low-resistance profile drug is chosen from the start. The effect is due to both
      the reduction in complications of cirrhosis and the prevention of the development
      of cirrhosis. CONCLUSION: Long-term antiviral therapy with a strategy that
      minimizes or controls resistance will have a major preventive effect on liver
      related mortality and morbidity.

PMID- 19585617
TI  - Cyclooxygenase-2 prevents fas-induced liver injury through up-regulation of
      epidermal growth factor receptor.
AB  - Cyclooxygenase-2 (COX-2)-derived prostaglandins participate in a number of
      pathophysiological responses such as inflammation, carcinogenesis, and modulation
      of cell growth and survival. This study used complementary approaches of COX-2
      transgenic (Tg) and knockout (KO) mouse models to evaluate the mechanism of COX-2
      in Fas-induced hepatocyte apoptosis and liver failure in vivo. We generated Tg
      mice with targeted expression of COX-2 in the liver by using the albumin promoter
      enhancer-driven vector. The COX-2 Tg, COX-2 KO, and wild-type mice were treated
      with the anti-Fas antibody Jo2 (0.5 microg/g of body weight) for 4 to 6 hours,
      and the extent of liver injury was assessed by histopathology, serum
      aminotransferases, TUNEL staining, and caspase activation. The COX-2 Tg mice
      showed resistance to Fas-induced liver injury in comparison with the wild-type
      mice; this was reflected by the lower alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) levels, less liver damage, and less hepatocyte
      apoptosis (P < 0.01). In contrast, the COX-2 KO mice showed significantly higher
      serum ALT and AST levels, more prominent hepatocyte apoptosis, and higher levels
      of caspase-8, caspase-9, and caspase-3 activity than the wild-type mice (P <
      0.01). The COX-2 Tg livers expressed higher levels of epidermal growth factor
      receptor (EGFR) than the wild-type controls; the COX-2 KO livers expressed the
      lowest levels of EGFR. Pretreatment with a COX-2 inhibitor (NS-398) or an EGFR
      inhibitor (AG1478) exacerbated Jo2-mediated liver injury and hepatocyte
      apoptosis. CONCLUSION: These findings demonstrate that COX-2 prevents Fas-induced
      hepatocyte apoptosis and liver failure at least in part through up-regulation of
      EGFR.

PMID- 19585618
TI  - Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic
      steatohepatitis: a multicenter validation study.
AB  - Liver biopsy remains the gold standard for diagnosing nonalcoholic
      steatohepatitis (NASH). We have recently demonstrated that plasma cytokeratin 18
      (CK-18) fragment levels correlate with the magnitude of hepatocyte apoptosis and
      independently predict the presence of NASH. The goal of this study was to
      validate the use of this biomarker for NASH diagnosis. The study was an ancillary
      study of the NASH Clinical Research Network (NASH CRN). Our cohort consisted of
      139 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) from
      eight CRN participant centers across the United States and 150 age-matched
      healthy controls. CK-18 fragments were measured using a specific enzyme-linked
      immunosorbent assay. Histology was assessed centrally by study pathologists. CK
      18 fragments were markedly increased in patients with NASH versus those without
      NASH and borderline diagnosis (median [25th, 75th percentile], 335 [196, 511],
      194 [151, 270], 200 [148, 284], respectively; P < 0.001). Moreover, the odds of
      having fibrosis on liver biopsy increased with increasing plasma CK-18 fragment
      levels (P < 0.001). On multivariate regression analysis, CK-18 fragments remained
      an independent predictor of NASH after adjusting for variables associated with CK
      18 fragments or NASH on univariate analysis (fibrosis, alanine aminotransferase,
      aspartate aminotransferase, age, biopsy length). The area under the receiver
      operating characteristic curve for NASH diagnosis was estimated to be 0.83 (0.75,
      0.91). CONCLUSION: Determination of CK-18 fragments in the blood predicts
      histological NASH and severity of disease in a large, diverse population of
      patients with biopsy-proven NAFLD, supporting the potential usefulness of this
      test in clinical practice.

PMID- 19585620
TI  - What's in a NAme?

PMID- 19585619
TI  - Interleukin 27 and viral hepatitis: smarter than the average cytokine.

PMID- 19585621
TI  - Outcomes of a patient-to-patient outbreak of genotype 3a hepatitis C.
AB  - Between March 2000 and July 2001, at least 99 persons acquired a hepatitis C
      virus genotype 3a (HCV-3a) infection in an oncology clinic. This nosocomial HCV
      outbreak provided an opportunity to examine the subsequent clinical course in a
      well-defined cohort. This was a retrospective/prospective observational study of
      the short-term significant health outcomes of a large, single-source, patient-to
      patient HCV-3a outbreak. Outbreak patients or their legal representatives
      consenting to study were enrolled between September 2002 and December 2007. We
      measured history and physical examinations, medical records, HCV serology, HCV
      RNA and genotype, liver enzymes, histology, response to antiviral therapy, and
      liver-related morbidity and mortality. Sixty-four of the 99 known HCV-3a outbreak
      patients participated. During a 6-year period, six patients developed life
      threatening complications from liver disease, three died, one received a liver
      transplant, and two were stable after esophageal variceal banding or diuretic
      therapy of ascites. Thirty-three patients underwent antiviral therapy, with 28
      achieving a sustained viral remission. One patient acquired HCV-3a infection
      sexually from an outbreak patient and was successfully treated. Eleven study
      patients died of malignancy, including two that had achieved a sustained viral
      remission after antiviral therapy. CONCLUSION: Our patient cohort had a
      nosocomial source and an oncologic or hematologic comorbidity. Compared with
      previous HCV outcome studies, a patient-to-patient HCV outbreak in an oncology
      clinic exhibited significant morbidity and mortality. Attention is needed to the
      public health risk of nosocomial HCV transmission, emphasizing infection control,
      early diagnosis, and therapy.

PMID- 19585622
TI  - MicroRNAs involved in tumor suppressor and oncogene pathways: implications for
      hepatobiliary neoplasia.
AB  - MicroRNAs are a class of small regulatory RNAs that function to modulate protein
      expression. This control allows for fine-tuning of the cellular phenotype,
      including regulation of proliferation, cell signaling, and apoptosis; not
      surprisingly, microRNAs contribute to liver cancer biology. Recent investigations
      in human liver cancers and tumor-derived cell lines have demonstrated decreased
      or increased expression of particular microRNAs in hepatobiliary cancer cells.
      Based on predicted and validated protein targets as well as functional
      consequences of altered expression, microRNAs with decreased expression in liver
      tumor cells may normally aid in limiting neoplastic transformation. Conversely,
      selected microRNAs that are up-regulated in liver tumor cells can promote
      malignant features, contributing to carcinogenesis. In addition, microRNAs
      themselves are subject to regulated expression, including regulation by tumor
      suppressor and oncogene pathways. This review will focus on the expression and
      function of cancer-related microRNAs, including their intimate involvement in
      tumor suppressor and oncogene signaling networks relevant to hepatobiliary
      neoplasia.

PMID- 19585623
TI  - Hepatocellular adenoma management and phenotypic classification: the Bordeaux
      experience.
AB  - We took advantage of the reported genotype/phenotype classification to analyze
      our surgical series of hepatocellular adenoma (HCA). The series without specific
      known etiologies included 128 cases (116 women). The number of nodules varies
      from single, <5, and >or=5 in 78, 38, and 12 cases, respectively. The resection
      was complete in 95 cases. We identified 46 HNF1alpha-inactivated HCAs (44 women),
      63 inflammatory HCAs (IHCA, 53 women) of which nine were also beta-catenin
      activated, and seven beta-catenin-activated HCAs (all women); six additional
      cases had no known phenotypic marker and six others could not be phenotypically
      analyzed. Twenty-three of 128 HCAs showed bleeding. No differences were observed
      in solitary or multiple tumors in terms of hemorrhagic manifestations between
      groups. In contrast, differences were observed between the two main groups.
      Steatosis (tumor), microadenomas (resected specimen), and additional benign
      nodules were more frequently observed in HNF1alpha-inactivated HCAs (P < 0.01)
      than in IHCAs. Body mass index > 25, peliosis (tumor), and steatosis in
      background liver were more frequent in IHCA (P < 0.01). After complete resection,
      new HCAs in the centimetric range were more frequently found during follow-up (>1
      year) in HNF1alpha-inactivated HCA. After incomplete resection (HCA left in
      nonresected liver), the majority of HCA remained stable in the two main groups
      and even sometimes regressed. Six patients of 128 developed hepatocellular
      carcinoma (HCC) (all were beta-catenin-activated, whether inflammatory or not).
      CONCLUSION: There were noticeable clinical differences between HNF1alpha
      inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related
      to the number of HCAs; beta-catenin-activated HCAs are at higher risk of HCC. As
      a consequence, we believe that management of HCA needs to be adapted to the
      phenotype of these tumors.

PMID- 19585624
TI  - SiC: a photocathode for water splitting and hydrogen storage.

PMID- 19585625
TI  - Molecular mechanism of inhibition of the human protein complex Hsp90-Cdc37, a
      kinome chaperone-cochaperone, by triterpene celastrol.

PMID- 19585627
TI  - Low-coordinate boride ligands: a true trimetalloborane.

PMID- 19585626
TI  - A low-temperature molecular approach to highly conductive tin-rich indium tin
      oxide thin films with durable electro-optical performance.

PMID- 19585629
TI  - A color-tunable europium complex emitting three primary colors and white light.

PMID- 19585630
TI  - Self-assembled ABC triblock copolymer double and triple helices.

PMID- 19585628
TI  - Axial chirality control of gold(biphep) complexes by chiral anions: application
      to asymmetric catalysis.

PMID- 19585631
TI  - Complete stereoretention in the rhodium-catalyzed 1,2-addition of chiral
      secondary and tertiary alkyl potassium trifluoroborate salts to aldehydes.

PMID- 19585632
TI  - Titanosilsesquioxanes embedded in synthetic clay as a hybrid material for polymer
      science.

PMID- 19585633
TI  - Highly chemoselective nickel-catalyzed three-component cross-trimerization of
      three distinct alkynes leading to 1,3-dien-5-ynes.

PMID- 19585634
TI  - Oxidation of catecholboron enolates with TEMPO.

PMID- 19585635
TI  - Trimeric cyclic assemblies of calix[4]arene-tethered bismerocyanines.

PMID- 19585636
TI  - Singlet oxygen production upon two-photon excitation of TiO2 in chloroform.
AB  - Singlet oxygen ((1)O(2)) signals observed upon illumination at 532 nm are a
      consequence of TiO(2) excitation in a two-photon process, and at 355 nm in a one
      photon pathway. After corrections for light reflectance, the relative quantum
      yields of (1)O(2) production are 0.23+/-0.01 and 0.22+/-0.02 for 532 and 355 nm
      excitation, respectively. Total quenching rate constants of (1)O(2) removal by
      TiO(2) particles are near the diffusion-controlled rate limit. By employing
      (1)O(2) as a probe, we have established an efficient and simple method to
      elucidate the nature of TiO(2) photoexcitation.

PMID- 19585637
TI  - A simple electrochemical cytosensor array for dynamic analysis of carcinoma cell
      surface glycans.

PMID- 19585638
TI  - Unnatural rigid scaffolds targeting the bacterial ribosome.

PMID- 19585639
TI  - Spatiotemporal kinetics in solution studied by time-resolved X-ray liquidography
      (solution scattering).
AB  - Information about temporally varying molecular structure during chemical
      processes is crucial for understanding the mechanism and function of a chemical
      reaction. Using ultrashort optical pulses to trigger a reaction in solution and
      using time-resolved X-ray diffraction (scattering) to interrogate the structural
      changes in the molecules, time-resolved X-ray liquidography (TRXL) is a direct
      tool for probing structural dynamics for chemical reactions in solution. TRXL can
      provide direct structural information that is difficult to extract from ultrafast
      optical spectroscopy, such as the time dependence of bond lengths and angles of
      all molecular species including short-lived intermediates over a wide range of
      times, from picoseconds to milliseconds. TRXL elegantly complements ultrafast
      optical spectroscopy because the diffraction signals are sensitive to all
      chemical species simultaneously and the diffraction signal from each chemical
      species can be quantitatively calculated from its three-dimensional atomic
      coordinates and compared with experimental TRXL data. Since X-rays scatter from
      all the atoms in the solution sample, solutes as well as the solvent, the
      analysis of TRXL data can provide the temporal behavior of the solvent as well as
      the structural progression of all the solute molecules in all the reaction
      pathways, thus providing a global picture of the reactions and accurate branching
      ratios between multiple reaction pathways. The arrangement of the solvent around
      the solute molecule can also be extracted. This review summarizes recent
      developments in TRXL, including technical innovations in synchrotron beamlines
      and theoretical analysis of TRXL data, as well as several examples from simple
      molecules to an organometallic complex, nanoparticles, and proteins in solution.
      Future potential applications of TRXL in femtosecond studies and biologically
      relevant molecules are also briefly mentioned.

PMID- 19585640
TI  - Metal-pi interactions dominate in the solid-state structures of molecular
      heterobimetallic alkali-metal-europium(II) aryloxo complexes.
AB  - Treatment of Eu metal, 2,6-diphenylphenol (HOdpp), and MOdpp (M=Na, K) at
      elevated temperature in the presence of mercury afforded heterobimetallic
      complexes which were structurally characterized after crystallization from
      toluene. The structures of [MEu(Odpp)(3)]nPhMe (M=Na, n=1, 1; K, n=2.5, 2)
      consist solely of bridging aryloxide ligands and feature extensive pi-Ph-metal
      interactions. Rather than a heterobimetallic species, treatment of Eu metal and
      HOdpp with LiOdpp under similar conditions afforded a number of products,
      including a mixed-valent europium complex, [Eu(2)(Odpp)(3)][Eu(Odpp)(4)]4 PhMe
      (3). The structural framework of the [Eu(2)(Odpp)(3)](+) cation of 3 is similar
      to that of the molecular heterobimetallics 1 and 2, including the presence of pi
      Ph-Eu interactions. The reluctance of the reaction to provide a Eu/Li
      heterobimetallic complex was exemplified by the simultaneous crystallization of
      [Eu(2)(Odpp)(4)]PhMe (6) and the homoleptic cubane [Li(4)(Odpp)(4)]2 C(6)H(14)
      (5) from toluene/hexane.

PMID- 19585641
TI  - Systematic studies using 2-(1-adamantylethynyl)pyrimidine-5-carbaldehyde as a
      starting material in Soai's asymmetric autocatalysis.
AB  - Herein, we present a new substrate for the Soai reaction, which has an
      adamantylethynyl residue (1 g) and exhibits asymmetric autocatalysis, yielding
      products with enantiomeric excesses above 99%. For the first time, all reactions
      were performed on a parallel synthesizer system to ensure identical reaction
      conditions. A detailed systematic study of reaction parameters was performed and
      we report the highest enhancements of enantiomeric excess reported so far in the
      Soai reaction in one reaction cycle (7.2-->94.1% ee or 3.1-->92.1% ee). Our
      results led to a set of reaction parameters that yield reproducible results.
      Therefore, our new starting material 1 g is suitable for systematic and
      mechanistic studies on this remarkable reaction. A series of experiments designed
      to quantify the amplification of enantiomeric excess demonstrated that the
      reaction can be used in principle as a tool for the detection of low enantiomeric
      excesses: under definite conditions, an unknown low enantiomeric excess (0.1-7%)
      was amplified to a detectable one. A back calculation to the original value
      offers a new method for the determination of small enantiomeric excesses.

PMID- 19585642
TI  - Stereocontrolled cyclic nitrone cycloaddition strategy for the synthesis of
      pyrrolizidine and indolizidine alkaloids.
AB  - The synthesis of polyhydroxylated indolizidines and pyrrolizidines belonging to
      the class of iminosugars, endowed with a vast and assorted biological activity,
      can be achieved in a straightforward manner by a general strategy consisting of a
      highly stereoselective 1,3-dipolar cycloaddition of polyhydroxylated pyrroline-N
      oxides followed by simple transformations of the isoxazolidine adducts. The
      strategy allows the complete control of the relative and absolute stereochemistry
      of the numerous stereogenic centers decorating these compounds.

PMID- 19585643
TI  - Facile cyclometalation reactions of Cp-zirconium complexes with weakly Lewis
      acidic pendent boron functionalities.

PMID- 19585644
TI  - Synthesis of 2-C-branched oligo(glyco-amino acid)s (OGAAs) by ring opening of 1,2
      cyclopropanecarboxylated sugar donors.

PMID- 19585645
TI  - UF6 and UF4 in liquid ammonia: [UF7(NH3)]3- and [UF4(NH3)4].
AB  - From the reaction of uranium hexafluoride UF6 with dry liquid ammonia, the
      [UF7(NH3)]3- anion and the [UF4(NH3)4] molecule were isolated and identified for
      the first time. They are found in signal-green crystals of trisammonium
      monoammine heptafluorouranate(IV) ammonia (1:1; [NH4]3[UF7(NH3)].NH3) and emerald
      green crystals of tetraammine tetrafluorouranium(IV) ammonia (1:1;
      [UF4(NH3)4].NH3). [NH4]3[UF7(NH3)].NH3 features discrete [UF7(NH3)]3- anions with
      a coordination geometry similar to a bicapped trigonal prism, hitherto unknown
      for U(IV) compounds. The emerald-green [UF4(NH3)4].NH3 contains discrete
      tetraammine tetrafluorouranium(IV) [UF4(NH3)4] molecules. [UF4(NH3)4].NH3 is not
      stable at room temperature and forms pastel-green [UF4(NH3)4] as a powder that is
      surprisingly stable up to 147 degrees C. The compounds are the first structurally
      characterized ammonia complexes of uranium fluorides.

PMID- 19585646
TI  - A simple and efficient catalytic system for N-arylation of imidazoles in water.

PMID- 19585647
TI  - Iron-substituted polyoxotungstates as inorganic synzymes: evidence for a
      biomimetic pathway in the catalytic oxygenation of catechols.

PMID- 19585648
TI  - Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core
      promoter, which is dependent on nuclear-located RING domain.
AB  - Members of the tripartite motif (TRIM) family are a part of the innate immune
      system to counter intracellular pathogens. TRIM22 has been reported to possess
      antiretroviral activity. Here we report that TRIM22 is involved in antiviral
      immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a
      strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit
      HBV gene expression and replication in a cell culture system as well as in a
      mouse model system. Importantly, it was found that TRIM22 could inhibit the
      activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22
      lacking the C terminal SPRY domain lost this activity. Further study showed that
      the SPRY domain deletion mutant was localized exclusively to the cytoplasm of
      HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as
      expected for a transcriptional suppressor. Interestingly, although RING domain
      mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP
      activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the
      nuclear-located RING domain. CONCLUSION: These findings suggest that TRIM22,
      which exhibits anti-HBV activity by acting as a transcriptional suppressor, may
      play an important role in the clearance of HBV.

PMID- 19585649
TI  - The myth of occult hepatitis C infection.

PMID- 19585650
TI  - A call for attention and trials on hepatitis B e antigen-negative, alanine
      aminotransferase-normal chronic hepatitis B virus infection.

PMID- 19585651
TI  - Liver biopsy in hepatitis C virus carriers with normal alanine aminotransferase
      levels.

PMID- 19585652
TI  - Overexpression of far upstream element binding proteins: a mechanism regulating
      proliferation and migration in liver cancer cells.
AB  - Microtubule-dependent effects are partly regulated by factors that coordinate
      polymer dynamics such as the microtubule-destabilizing protein stathmin
      (oncoprotein 18). In cancer cells, increased microtubule turnover affects cell
      morphology and cellular processes that rely on microtubule dynamics such as
      mitosis and migration. However, the molecular mechanisms deregulating modifiers
      of microtubule activity in human hepatocarcinogenesis are poorly understood.
      Based on profiling data of human hepatocellular carcinoma (HCC), we identified
      far upstream element binding proteins (FBPs) as significantly coregulated with
      stathmin. Coordinated overexpression of two FBP family members (FBP-1 and FBP-2)
      in >70% of all analyzed human HCCs significantly correlated with poor patient
      survival. In vitro, FBP-1 predominantly induced tumor cell proliferation, while
      FBP-2 primarily supported migration in different HCC cell lines. Surprisingly,
      reduction of FBP-2 levels was associated with elevated FBP-1 expression,
      suggesting a regulatory interplay of FBP family members that functionally
      discriminate between cell division and mobility. Expression of FBP-1 correlated
      with stathmin expression in HCC tissues and inhibition of FBP-1 but not of FBP-2
      drastically reduced stathmin at the transcript and protein levels. In contrast,
      further overexpression of FBP-1 did not affect stathmin bioavailability.
      Accordingly, analyzing nuclear and cytoplasmic areas of HCC cells revealed that
      reduced FBP-1 levels affected cell morphology and were associated with a less
      malignant phenotype. CONCLUSION: The coordinated activation of FBP-1 and FBP-2
      represents a novel and frequent pro-tumorigenic mechanism promoting proliferation
      (tumor growth) and motility (dissemination) of human liver cancer cells. FBPs
      promote tumor-relevant functions by at least partly employing the microtubule
      destabilizing factor stathmin and represent a new potential target structure for
      HCC treatment.

PMID- 19585653
TI  - A phase III study of the safety and efficacy of viramidine versus ribavirin in
      treatment-naive patients with chronic hepatitis C: ViSER1 results.
AB  - Pegylated interferon (peg-IFN) and ribavirin (RBV) are effective in eradicating
      the hepatitis C virus in more than half of patients. However, anemia arising from
      RBV-induced hemolysis can prompt dose reductions and lower sustained virologic
      response (SVR) rates. In early clinical trials, Viramidine (VRD, renamed
      taribavirin), an RBV prodrug, was associated with less anemia and VRD given at
      600 mg twice daily (BID) appeared to provide the best safety with comparable
      efficacy to RBV. The phase III Viramidine's Safety and Efficacy versus Ribavirin
      1 (ViSER1) study randomized 972 treatment-naive patients with chronic hepatitis C
      to fixed-dose VRD (600 mg BID) or weight-based RBV (1000 or 1200 mg/day), each
      given with peg-IFN alfa-2b at 1.5 microg/kg/week. The primary efficacy endpoint
      was SVR rate, and the primary safety endpoint was hemoglobin (Hb) event rate
      (percent of patients with Hb < 10 g/dL or at least a 2.5-g/dL decrease from
      baseline). SVR rates were 37.7% with VRD (244/647) and 52.3% with RBV (170/325).
      Thus, the ViSER1 study failed to demonstrate the primary noninferiority efficacy
      endpoint. Significantly fewer patients had Hb events with VRD (353/647; 54.6%)
      compared to those with RBV (272/325; 83.7%) (P < 0.001), and significantly fewer
      developed anemia (Hb < 10 g/dL) with VRD (34/647; 5.3%) compared to those with
      RBV (76/325; 23.5%) (P < 0.001). CONCLUSION: Fixed doses of VRD failed to
      demonstrate noninferiority to RBV in producing SVR rates. The incidence of anemia
      was approximately four-fold significantly lower with VRD than with RBV. These
      results suggest fixed-dose VRD given 600 mg BID is insufficient to treat patients
      with chronic hepatitis C; a weight-based dosing trial of viramidine is currently
      under way.

PMID- 19585654
TI  - Identification of microRNA-181 by genome-wide screening as a critical player in
      EpCAM-positive hepatic cancer stem cells.
AB  - MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene
      expression with functional links to tumorigenesis. Hepatocellular carcinoma (HCC)
      is the most common type of liver cancer, and it is heterogeneous in clinical
      outcomes and biological activities. Recently, we have identified a subset of
      highly invasive epithelial cell adhesion molecule (EpCAM)(+) HCC cells from alpha
      fetoprotein (AFP)(+) tumors with cancer stem/progenitor cell features, that is,
      the abilities to self-renew, differentiate, and initiate aggressive tumors in
      vivo. Here, using a global microarray-based miRNA profiling approach followed by
      validation with quantitative reverse transcription polymerase chain reaction, we
      have demonstrated that conserved miR-181 family members were up-regulated in
      EpCAM(+)AFP(+) HCCs and in EpCAM(+) HCC cells isolated from AFP(+) tumors.
      Moreover, miR-181 family members were highly expressed in embryonic livers and in
      isolated hepatic stem cells. Importantly, inhibition of miR-181 led to a
      reduction in EpCAM(+) HCC cell quantity and tumor initiating ability, whereas
      exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM(+)
      HCC cells. We have found that miR-181 could directly target hepatic
      transcriptional regulators of differentiation (for example, caudal type homeobox
      transcription factor 2 [CDX2] and GATA binding protein 6 [GATA6]) and an
      inhibitor of Wnt/beta-catenin signaling (nemo-like kinase [NLK]). Taken together,
      our results define a novel regulatory link between miR-181s and human EpCAM(+)
      liver cancer stem/progenitor cells and imply that molecular targeting of miR-181
      may eradicate HCC.

PMID- 19585655
TI  - Adipokines in liver diseases.
AB  - Adipokines are polypeptides secreted in the adipose tissue in a regulated manner.
      While some of these molecules are expressed only by adipocytes, resident and
      infiltrating macrophages and components of the vascular stroma markedly
      contribute to expression of other adipokines. As a result, adipose tissue
      inflammation is associated with a modification in the pattern of adipokine
      secretion. Leptin, adiponectin, and resistin are the best-studied molecules in
      this class, but cytokines such as tumor necrosis factor or interleukin-6 are also
      secreted at high levels by the adipose tissue. Several other molecules have been
      recently identified and are actively investigated. Adipokines interfere with
      hepatic injury associated with fatty infiltration, differentially modulating
      steatosis, inflammation, and fibrosis. Several studies have investigated plasma
      levels of adiponectin in patients with nonalcoholic fatty liver disease, to
      establish correlations with the underlying state of insulin resistance and with
      the type and severity of hepatic damage. Hepatitis C is another disease where
      adipokines may represent a link between viral infection, steatosis, and metabolic
      disturbances. Identification of the mediators secreted by expanded adipose tissue
      and their pathogenic role is pivotal in consideration of the alarming increase in
      the prevalence of obesity and of the detrimental role that this condition exerts
      on the course of liver diseases.

PMID- 19585656
TI  - Incidence, risk factors, and survival of hepatocellular carcinoma in primary
      biliary cirrhosis: comparative analysis from two centers.
AB  - The limited information and divergent results on the prevalence, incidence, and
      risk factors for hepatocellular carcinoma (HCC) in patients with primary biliary
      cirrhosis (PBC) may be due to the low prevalence of the disease and geographical
      and environmental differences. Therefore, we analyzed the incidence, prevalence,
      survival, and risk factors for HCC in patients with PBC from two European centers
      (389 from Barcelona, Spain, and 327 from Padova, Italy) followed up for 9.3 +/-
      6.5 years. Gender, age, smoking habit, alcohol consumption, presence of hepatitis
      B surface antigen (HBsAg) or hepatitis C virus antibodies (anti-HCV), and
      advanced histological stage (III-IV) were evaluated as risk factors for tumor
      development. Twenty-four patients (13 from Barcelona and 11 from Padova)
      developed HCC. The prevalence of HCC was similar in Barcelona (3.34%) and Padova
      (3.36%). The incidence was 0.35 and 0.37 per 100 patient-years, respectively.
      Male gender, age >52 years, smoking habit, alcohol >40 g/day, HBsAg, and anti-HCV
      were not associated with HCC. Advanced histological stage was the only factor
      associated with the development of HCC (odds ratio [OR]: 5.80, 95% confidence
      interval [CI]: 2.34-14.38, P < 0.001). When analyzing the two series separately,
      male gender was associated with higher likelihood of HCC in Padova (OR: 8.09, 95%
      CI: 1.93-33.8, P < 0.01). The median survival after the diagnosis of HCC was 36
      months. CONCLUSION: The prevalence and incidence of HCC is similar in Spain and
      Italy and the advanced histological stage is the only risk factor associated with
      the development of HCC in PBC. The slight disparities observed between the two
      series might be explained by patient features on diagnosis of liver disease.

PMID- 19585657
TI  - Identification of specificity and promiscuity of PDZ domain interactions through
      their dynamic behavior.
AB  - PDZ domains (PDZs), the most common interaction domain proteins, play critical
      roles in many cellular processes. PDZs perform their job by binding specific
      protein partners. However, they are very promiscuous, binding to more than one
      protein, yet selective at the same time. We examined the binding related dynamics
      of various PDZs to have insight about their specificity and promiscuity. We used
      full atomic normal mode analysis and a modified coarse-grained elastic network
      model to compute the binding related dynamics. In the latter model, we introduced
      specificity for each single parameter constant and included the solvation effect
      implicitly. The modified model, referred to as specific-Gaussian Network Model (s
      GNM), highlights some interesting differences in the conformational changes of
      PDZs upon binding to Class I or Class II type peptides. By clustering the residue
      fluctuation profiles of PDZs, we have shown: (i) binding selectivities can be
      discriminated from their dynamics, and (ii) the dynamics of different structural
      regions play critical roles for Class I and Class II specificity. s-GNM is
      further tested on a dual-specific PDZ which showed only Class I specificity when
      a point mutation exists on the betaA-betaB loop. We observe that the binding
      dynamics change consistently in the mutated and wild type structures. In
      addition, we found that the binding induced fluctuation profiles can be used to
      discriminate the binding selectivity of homolog structures. These results
      indicate that s-GNM can be a powerful method to study the changes in binding
      selectivities for mutant or homolog PDZs.

PMID- 19585658
TI  - Kinetic and binding effects in peptide substrate selectivity of matrix
      metalloproteinase-2: Molecular dynamics and QM/MM calculations.
AB  - Herein, we examine computationally the binding and hydrolysis reaction of the MMP
      2 enzyme with two peptide substrates selected by the enzyme from a phage peptide
      library. Molecular dynamics simulations of the Michaelis complexes (25 ns) allow
      us to characterize the main enzyme/substrate contacts. Subsequently MM-PBSA
      calculations using independent trajectories for the complexes and the free
      substrates provide relative binding energies in good agreement with the
      experimental K(M) results. Computational alanine scanning analyses of the
      enzyme/substrate interaction energies confirm the relevance of the P(3), P(2),
      and P(1)' side chains for ligand binding. Finally, the hydrolysis of both
      peptides taking place at the MMP-2 active site is explored by means of hybrid
      quantum mechanical/molecular mechanics calculations. The computed reaction
      mechanisms result in rate-determining energy barriers being in consonance with
      the experimental k(cat) values. Overall, the computational protocol seems to
      capture the subtle differences in binding and catalysis experimentally observed
      for the two peptide substrates. Some implications of our results for the future
      design of novel and more specific MMP-2 inhibitors are also discussed.

PMID- 19585659
TI  - Crystal structure of human diphosphoinositol phosphatase 1.

PMID- 19585660
TI  - Protein-protein interactions at an enzyme-substrate interface: characterization
      of transient reaction intermediates throughout a full catalytic cycle of
      Escherichia coli thioredoxin reductase.
AB  - A large collection of structural snapshots along a full catalytic cycle of
      Escherichia coli thioredoxin reductase (TrxR) has been generated and
      characterized using a combination of theoretical methods. Molecular models were
      built starting from the available X-ray crystallographic structures of dimeric
      wild-type TrxR in the flavin-oxidizing conformation and a C135S TrxR mutant
      enzyme in a flavin-reducing conformation "trapped" by a cross-link between Cys138
      of TrxR and Cys32 of C35S mutant thioredoxin (Trx). The transition between these
      two extreme states, which is shown to be reproduced in a normal mode analysis, as
      well as natural cofactor binding and dissociation, were simulated for the wild
      type species using unrestrained and targeted molecular dynamics following docking
      of oxidized Trx to reduced TrxR. The whole set of simulations provides a
      comprehensive structural framework for understanding the mechanism of disulfide
      reduction in atomic detail and identifying the most likely intermediates that
      facilitate entry of NADPH and exit of NADP(+). The crucial role assigned to Arg73
      and Lys36 of Trx in substrate binding and complex stabilization was ascertained
      when R73G, R73D, and K36A site-directed mutants of Trx were shown to be impaired
      to different extents in their ability to be reduced by TrxR. On the basis of
      previous findings and the results reported herein, E. coli TrxR appears as a
      beautifully engineered molecular machine that is capable of synchronizing
      cofactor capture and ejection with substrate binding and redox activity through
      an interdomain twisting motion.

PMID- 19585661
TI  - Prediction of global and local model quality in CASP8 using the ModFOLD server.
AB  - The development of effective methods for predicting the quality of three
      dimensional (3D) models is fundamentally important for the success of tertiary
      structure (TS) prediction strategies. Since CASP7, the Quality Assessment (QA)
      category has existed to gauge the ability of various model quality assessment
      programs (MQAPs) at predicting the relative quality of individual 3D models. For
      the CASP8 experiment, automated predictions were submitted in the QA category
      using two methods from the ModFOLD server-ModFOLD version 1.1 and ModFOLDclust.
      ModFOLD version 1.1 is a single-model machine learning based method, which was
      used for automated predictions of global model quality (QMODE1). ModFOLDclust is
      a simple clustering based method, which was used for automated predictions of
      both global and local quality (QMODE2). In addition, manual predictions of model
      quality were made using ModFOLD version 2.0--an experimental method that combines
      the scores from ModFOLDclust and ModFOLD v1.1. Predictions from the ModFOLDclust
      method were the most successful of the three in terms of the global model
      quality, whilst the ModFOLD v1.1 method was comparable in performance to other
      single-model based methods. In addition, the ModFOLDclust method performed well
      at predicting the per-residue, or local, model quality scores. Predictions of the
      per-residue errors in our own 3D models, selected using the ModFOLD v2.0 method,
      were also the most accurate compared with those from other methods. All of the
      MQAPs described are publicly accessible via the ModFOLD server at:
      http://www.reading.ac.uk/bioinf/ModFOLD/. The methods are also freely available
      to download from: http://www.reading.ac.uk/bioinf/downloads/.

PMID- 19585662
TI  - Clinical evaluation of a simple image cytometer for CD4 enumeration on HIV
      infected patients.
AB  - BACKGROUND: Affordable, easy-to-use, and reliable CD4(+) T lymphocyte enumeration
      systems are needed in resource-constrained settings to monitor HIV. METHODS: A
      simple image cytometer was used to count fluorescently labeled CD4(+) T and
      CD8(+) T lymphocytes from CD3 immunomagnetically selected cells on blood
      specimens of 460 HIV-1-infected patients in Siriraj Hospital, Bangkok, Thailand.
      Results were compared with flow cytometry (FCM). RESULTS: CD4(+) T lymphocyte
      counts by image cytometer were comparable (R > or = 0.97) with those by the
      FACSCount and the FACScan with a bias of 7.3 and 9.1%, respectively. At very low
      CD4(+) T lymphocyte counts (< or =50/microl) some over-count outliers were
      observed by the FACScan and image cytometer when compared with the FACSCount. For
      CD8 enumeration, the image cytometer showed a good correlation (R = 0.96) and a
      consistent undercount (approximately 17%) when compared with the FACSCount.
      CONCLUSIONS: Evaluation of the image cytometer for CD4 and CD8 enumeration
      demonstrated comparable results with FCM on a population of HIV-1-infected
      patients. The image cytometer is a good alternative method for point-of-care
      settings in resource-constrained countries.

PMID- 19585663
TI  - Mitochondrial ATP-independent chaperones.
AB  - Mitochondria possess a dedicated-chaperone system in the intermembrane space, the
      small Tims that are ubiquitous in all eukaryotes from yeast to man. They escort
      membrane proteins to the outer or the inner membrane for proper insertion. These
      mitochondrial chaperones do not require external energy to perform their function
      and have structural similarities to other ATP-independent chaperones. Here, we
      discuss their structural properties and how these relate to their chaperoning
      function in the mitochondrial intermembrane space.

PMID- 19585664
TI  - Caring for a sibling with anorexia nervosa: a qualitative study.
AB  - OBJECTIVE: Few studies have explored eating disorders from the perspective of non
      affected siblings. The aim of this investigation was to explore the unique
      experiences and challenges of siblings of women with anorexia nervosa (AN).
      METHOD: Twelve semi-structured qualitative interviews were conducted with sibling
      participants to ascertain their perspective of caring for a sister with chronic
      AN. RESULTS: Qualitative analyses gleaned six themes: (1) the sibling role as
      protector and mediator; (2) familial factors that influence and reinforce these
      sibling roles; (3) consequences and benefits of AN to non-affected sibling; (4)
      coping strategies; (5) current and future intentions of caregiving and (6)
      professional and informal support. DISCUSSION: The findings from this qualitative
      study provide a window into the perceptions, feelings, and roles of siblings of
      women afflicted with AN. An intervention guided by the elicited themes may
      facilitate family functioning that is more adaptive for both siblings.

PMID- 19585666
TI  - Advances in researches on the immune dysregulation and therapy of severe acute
      pancreatitis.
AB  - During the development and progression of severe acute pancreatitis (SAP),
      conspicuous immune dysregulation develops, which is mainly manifested as
      excessive immune response in the early stage and immunosuppression in the late
      stage. This process involves complex changes in a variety of immune molecules and
      cells, such as cytokines, complements, lymphocytes, and leukocytes. With the
      gradual deepening of studies on the development and progression of SAP, the role
      of immune dysregulation in the pathogenesis of SAP has attracted more and more
      attention. In this article, we review the advances in research on the immune
      dysregulation in SAP and the immunotherapy of this disease through exploring the
      formation of excessive immune response and immune suppression as well as their
      mutual transformation.

PMID- 19585665
TI  - Mitochondrial functions on oocytes and preimplantation embryos.
AB  - Oocyte quality has long been considered as a main limiting factor for in vitro
      fertilization (IVF). In the past decade, extensive observations demonstrated that
      the mitochondrion plays a vital role in the oocyte cytoplasm, for it can provide
      adenosine triphosphate (ATP) for fertilization and preimplantation embryo
      development and also act as stores of intracellular calcium and proapoptotic
      factors. During the oocyte maturation, mitochondria are characterized by distinct
      changes of their distribution pattern from being homogeneous to heterogeneous,
      which is correlated with the cumulus apoptosis. Oocyte quality decreases with the
      increasing maternal age. Recent studies have shown that low quality oocytes have
      some age-related dysfunctions, which include the decrease in mitochondrial
      membrane potential, increase of mitochondrial DNA (mtDNA) damages, chromosomal
      aneuploidies, the incidence of apoptosis, and changes in mitochondrial gene
      expression. All these dysfunctions may cause a high level of developmental
      retardation and arrest of preimplantation embryos. It has been suggested that
      these mitochondrial changes may arise from excessive reactive oxygen species
      (ROS) that is closely associated with the oxidative energy production or calcium
      overload, which may trigger permeability transition pore opening and subsequent
      apoptosis. Therefore, mitochondria can be seen as signs for oocyte quality
      evaluation, and it is possible that the oocyte quality can be improved by
      enhancing the physical function of mitochondria. Here we reviewed recent advances
      in mitochondrial functions on oocytes.

PMID- 19585667
TI  - Assessment of volumetric bone mineral density of the femoral neck in
      postmenopausal women with and without vertebral fractures using quantitative
      multi-slice CT.
AB  - OBJECTIVE: To demonstrate the validity and reliability of volumetric quantitative
      computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual
      energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD)
      measurements, and to compare the differences between the two techniques in
      discriminating postmenopausal women with osteoporosis-related vertebral fractures
      from those without. METHODS: Ninety subjects were enrolled and divided into three
      groups based on the BMD values of the lumbar spine and/or the femoral neck by
      DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <-2SD,
      with and without radiographically confirmed vertebral fracture (n=11 and 33,
      respectively). Group 3 comprised normal controls with BMD changes > or =-1SD
      (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal
      pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to
      calculate the following parameters: volumetric BMD values of trabecular bone
      (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck,
      femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD
      measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also
      were performed for each subject. RESULTS: The values of all seven parameters were
      significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal
      women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were
      significantly lower in postmenopausal women with vertebral fracture(s) [(109.8+/
      9.61) and (243.3+/-33.0) mg/cm3, respectively] than in those without [(148.9+/
      7.47) and (285.4+/-17.8) mg/cm(3), respectively] (P<0.05, respectively), but no
      significant differences were evident in AP-SPINE or NECK BMD. CONCLUSION: the
      femoral neck-derived volumetric BMD parameters using vQCT appeared better than
      the DXA-derived ones in discriminating osteoporotic postmenopausal women with
      vertebral fractures from those without. vQCT might be useful to evaluate the
      effect of osteoporotic vertebral fracture status on changes in bone mass in the
      femoral neck.

PMID- 19585668
TI  - Effects of carnosine on the evoked potentials in hippocampal CA1 region.
AB  - OBJECTIVE: To directly examine the effects of carnosine on neuronal excitation
      and inhibition in rat hippocampus in vivo. METHODS: Artificial cerebrospinal
      fluid with carnosine was directly administrated over the exposed rat hippocampus.
      The changes of neuron activity in the CA1 region of hippocampus were evaluated by
      orthodromically- and antidromically-evoked potentials, as well as paired-pulse
      stimulation paradigm. RESULTS: In both orthodromic and antidromic response
      potentials, carnosine transformed population spikes (PSs) with single spike into
      epileptiform multiple spikes. In addition, similar to the effect of (
      aminobutyric acid(A) (GABA(A)) antagonist picrotoxin, carnosine decreased paired
      pulse stimulating depression significantly. However, no significant change was
      observed in the spontaneous field potentials during the application of carnosine.
      CONCLUSION: The results indicate a disinhibition-induced excitation effect of
      carnosine on the CA1 pyramidal neurons. It provides important information against
      the application of carnosine as a potential anticonvulsant in clinical treatment.

PMID- 19585669
TI  - Protective effect of DNA-mediated immunization with liposome-encapsulated GRA4
      against infection of Toxoplasma gondii.
AB  - The dense granule protein 4 (GRA4) is a granular protein from Toxoplasma gondii,
      and is a candidate for vaccination against this parasite. In this study, the
      plasmid pcDNA3.1-GRA4 (pGRA4), encoding for the GRA4 antigen, was incorporated by
      the dehydration-rehydration method into liposomes composed of 16 mmol/L egg
      phosphatidylcholine (PC), 8 mmol/L dioleoyl phosphatidylethanolamine (DOPE), and
      4 mmol/L 1,2-diodeoyl-3-(trimethylammonium) propane (DOTAP). C57BL/6 mice and
      BALB/c mice were immunized intramuscularly three times with liposome-encapsulated
      pGRA4 to determine whether DNA immunization could elicit a protective immune
      response to T. gondii. Enzyme-linked immunosorbent assay (ELISA) of sera from
      immunized mice showed that liposome-encapsulated pGRA4 generated high levels of
      IgG antibodies to GRA4. Production of primary interferon (IFN)-gamma and
      interleukin (IL)-2 in GRA4-stimulated splenocytes from vaccinated mice suggested
      a modulated Th1-type response. 72.7% of C57BL/6 mice immunized with liposome
      encapsulated pGRA4 survived the challenge with 80 tissue cysts of ME49 strain,
      whereas C57BL/6 mice immunized with pGRA4 had only a survival rate of 54.5%. When
      immunized BALB/c mice were intraperitoneally challenged with 10(3) tachyzoites of
      the highly virulent RH strain, the survival time of mice immunized with liposome
      encapsulated pGRA4 was markedly longer than that of other groups. Our
      observations show that liposome-encapsulated pGRA4 enhanced the protective effect
      against infection of T. gondii.

PMID- 19585670
TI  - Features of intervertebral disc degeneration in rat's aging process.
AB  - OBJECTIVE: The age-related change is important part of degenerative disc disease.
      However, no appropriate animal model or objective evaluation index is available.
      This study aimed to investigate the features of intervertebral disc degeneration
      in aging process of rats. METHODS: 22-month-old Sprague-Dawley (SD) rats were
      used as spontaneously occurring intervertebral disc degeneration models and 6
      month-old rats as young controls. Expression of collagen types II and X was
      measured by immunohistochemistry. Degenerations of intervertebral discs were
      scored according to Miyamoto's method. Numbers and areas of afferent vascular
      buds were measured. The thicknesses of non-calcified and calcified layers were
      measured and statistically analyzed. RESULTS: There were less collagen type II
      expression and more collagen type X expression in the calcified layer of the
      cartilage endplates and nucleus pulposus in the rats of the aged group than in
      the young control. There were fewer and smaller afferent vascular buds in the
      rats of the aged group than in the young control group. The ratio of the non
      calcified to the calcified layers in the rats of the aged group significantly
      decreased, compared with that of the young control group (P<0.01). CONCLUSION:
      Rats can spontaneously establish intervertebral disc age-related degeneration.
      The expression of collagen types II and X, numbers and areas of afferent vascular
      buds, the ratio of the non-calcified to the calcified layers, and water and
      glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of
      intervertebral disc degeneration.

PMID- 19585671
TI  - Parthenolide inhibits proliferation of vascular smooth muscle cells through
      induction of G0/G1 phase cell cycle arrest.
AB  - OBJECTIVE: This study is to determine the effect of the natural product
      parthenolide, a sesquiterpene lactone isolated from extracts of the herb
      Tanacetum parthenium, on the proliferation of vascular smooth muscle cells
      (VSMCs). METHODS: Rat aortic VSMCs were isolated and cultured in vitro, and
      treated with different concentrations of parthenolide (10, 20 and 30 mumol/L).
      [(3)H]thymidine incorporation was used as an index of cell proliferation. Cell
      cycle progression and distribution were determined by flow cytometric analysis.
      Furthermore, the expression of several regulatory proteins relevant to VSMC
      proliferation including IkappaBalpha, cyclooxygenase-2 (Cox-2), p21, and p27 was
      examined to investigate the potential molecular mechanism. RESULTS: Treatment
      with parthenolide significantly decreased the [(3)H]thymidine incorporation into
      DNA by 30%~56% relative to control values in a dose-dependent manner (P<0.05).
      Addition of parthenolide also increased cell population at G(0)/G(1) phase by
      19.2%~65.7% (P<0.05) and decreased cell population at S phase by 50.7%~84.8%
      (P<0.05), which is consistent with its stimulatory effects on p21 and p27. In
      addition, parthenolide also increased IkappaBalpha expression and reduced Cox-2
      expression in a time-dependent manner. CONCLUSION: Our results show that
      parthenolide significantly inhibits the VSMC proliferation by inducing G(0)/G(1)
      cell cycle arrest. IkappaBalpha and Cox-2 are likely involved in such inhibitory
      effect of parthenolide on VSMC proliferation. These findings warrant further
      investigation on potential therapeutic implications of parthenolide on VSMC
      proliferation in vivo.

PMID- 19585672
TI  - Gender difference in the effect of daytime sleep on declarative memory for
      pictures.
AB  - OBJECTIVE: To investigate gender difference in the effects of daytime sleep on
      item and source memories, which are dissociable elements of declarative memory,
      and the effects of sleep on recollection and familiarity, which are two processes
      underlying recognition. METHODS: Participants saw a series of pictures with
      either blue or red background, and were then given a pretest for item and source
      memories. Then males and females respectively were randomly assigned either to a
      wake or a sleep condition. In the wake condition, participants remained awake
      until the posttest; in the sleep condition, participants slept for 1 h until
      awakened and asked to remain awake until the posttest. RESULTS: Daytime sleep
      contributed to retention of source memory rather than item memory in females,
      whereas males undergoing daytime sleep had a trend towards increased familiarity.
      For females, however, neither recollection nor familiarity appeared to be
      influenced by daytime sleep. CONCLUSION: The mechanism underlying gender
      difference may be linked with different memory traces resulting from different
      encoding strategies, as well as with different electrophysiological changes
      during daytime sleep.

PMID- 19585673
TI  - Video-assisted thoracoscopic surgery (VATS) for the treatment of hepatic
      hydrothorax: report of twelve cases.
AB  - BACKGROUND: Hepatic hydrothorax is defined as a significant pleural effusion in
      patients with liver cirrhosis and without underlying cardiopulmonary diseases.
      Treatment of hepatic hydrothorax remains a challenge at present. METHODS: Herein
      we share our experiences in the treatment of 12 patients with hepatic hydrothorax
      by video-assisted thoracoscopic surgery (VATS). Repair of the diaphragmatic
      defects, or pleurodesis by focal pleurectomy, talc spray, mechanical abrasion,
      electro-cauterization or injection was administered intraoperatively, and
      tetracycline intrapleural injection was used postoperatively for patients with
      prolonged (>7 d) high-output (>300 ml/d) pleural effusion. RESULTS: Out of the 12
      patients, 8 (67%) had uneventful postoperative course and did not require tube
      for drainage more than 3 months after discharge. In 4 (33%) patients the pleural
      effusion still recurred after discharge due to end-stage cirrhosis with massive
      ascites. CONCLUSION: We conclude that the repair of the diaphragmatic defect and
      pleurodesis through VATS could be an alternative of transjugular intrahepatic
      portal systemic shunt (TIPS) or a bridge to liver transplantation for patients
      with refractory hepatic hydrothorax. Pleurodesis with electrocauterization can be
      an alternative therapy if talc is unavailable.

PMID- 19585676
TI  - Some brain effects of stress may be reversible.

PMID- 19585674
TI  - Granulomatous hypophysitis: two case reports and literature review.
AB  - Granulomatous hypophysitis (GRH) is extremely rare and commonly presents with
      chronic inflammatory of the enlarged pituitary gland. In our study, 66-year-old
      and 57-year-old women, both Chinese, were diagnosed with GRH presenting
      preoperatively definite imageology characters as pituitary adenoma. The 66-year
      old woman presented with a year of headache, half a year of gradual decrease of
      visual acuity, and one month of right ptosis. Serum prolactin level was slightly
      elevated. Screening computed tomography (CT) scanning revealed typical low
      density mass found on the enlarged sella, which demonstrated invasive extension
      from the sella to the right cavernous sinus by contrast enhanced magnetic
      resonance imaging (MRI). Consequently, the patient was diagnosed with probable
      invasive pituitary adenoma. The other 57-year-old woman complained a light
      headache and had been previously treated as nonfunctional pituitary adenoma in
      other hospital. Finally these two patients underwent transsphenoidal microsurgery
      and were diagnosed with GRH according to postoperative histopathology. They then
      were treated with steroid. During the follow-up, the clinical symptoms such as
      headache, visual damage, and ptosis vanished, and the mass of the sellae
      dramatically shrank on repeated MR images. Clinically and radiologically, GRH is
      a rare sellar entity easily to be misdiagnosed as a pituitary adenoma. Trans
      sphenoidal surgery can decompress the optical nerve or oculomotornerve as a
      therapeutic strategy, and support biopsy or further pathological diagnosis.
      However, the hormonal therapy should be emphasized both as diagnostic and
      therapeutic strategies. Conservative and tentative steroid treatment should be
      performed in preoperative period without acute nerve damage.

PMID- 19585675
TI  - IgE myeloma with elevated level of serum CA125.
AB  - OBJECTIVE: To explore clinical and laboratory features and significance of
      detecting serum carbohydrate antigen 125 (CA125) in immunoglobulin E (IgE)
      multiple myeloma. METHODS: We reported the clinical findings of a male patient
      with IgE myeloma and elevated level of serum CA125 and reviewed the literature.
      RESULTS: Laboratory tests of this patient on admission showed extremely high
      serum IgE and CA125, a bone marrow aspirate revealed abnormal plasma cells (38.4%
      of nucleated cells: 16.4% mature and 22% atypical), and in bone marrow biopsy,
      immunoperoxidase staining showed positive cytoplasmic staining for IgE and kappa
      light chain within the vast majority of plasma cells. Computed tomography (CT)
      bone scans indicated wedge shape change and compressive fracture of thoracic
      vertebrae, and emission computed tomography (ECT) discovered multiple punctiform
      aggregation of radiation in both cervical ribs and spine. The serum IgE and CA125
      gradually decreased to normal limits after eight cycles of chemotherapy. This
      patient is alive well with an 18-month complete remission. CONCLUSION: We
      reported the first case of IgE myeloma with elevated level of serum CA125. To
      further evaluate clinical characteristics and significance of CA125 in IgE
      myeloma, more cases are needed.

PMID- 19585677
TI  - [Malnutrition in oncology: frequent symptoms, insufficiently detected and
      management].

PMID- 19585678
TI  - [Fruits, vegetables . . . but not antioxidant].

PMID- 19585679
TI  - [Mutations of IDH1 and 2 genes: a molecular diagnosis of low-grade gliomas].

PMID- 19585680
TI  - [The ubiquitin ligase CHIP, tumor suppressor in cancer of the breast?].

PMID- 19585681
TI  - [Nutrition and cancer: questions of balance].

PMID- 19585682
TI  - Standards of practice for culturally competent nursing care: a request for
      comments.

PMID- 19585684
TI  - Loss of land could threaten health of Sami people.

PMID- 19585683
TI  - Pakistan's refugees face uncertain future.

PMID- 19585685
TI  - Writing values.

PMID- 19585687
TI  - The last cigarette.

PMID- 19585686
TI  - Lenalidomide for the treatment of relapsed multiple myeloma.

PMID- 19585688
TI  - Cancer connections.

PMID- 19585689
TI  - Laparoscopic treatment of a spontaneous ovarian heterotopic pregnancy.
AB  - Spontaneous heterotopic pregnancies are uncommon, and ovarian implantations are
      even more unusual. Clinical symptoms, serial human chorionic gonadotropin levels
      and the presence of an intrauterine pregnancy on ultrasound are not reliable to
      diagnose a heterotopic pregnancy. A 27-year-old Gravida 2 Para 1 presented with a
      complaint of right lower quadrant sharp, cramping pain associated with nausea and
      vomiting. Ultrasound demonstrated an intrauterine pregnancy and a right adnexal
      mass. The right adnexal mass had a gestational sac with a fetal pole and positive
      fetal heart activity. A laparoscopic ovarian cystectomy was performed with
      preservation of the corpus luteum. A discussion of conservative versus radical
      treatment of the heterotopic pregnancy is presented.

PMID- 19585690
TI  - Tobacco-free in 2009.

PMID- 19585691
TI  - Pancreatic ascites: rare complication of a common disease.

PMID- 19585693
TI  - [New attitudes wanted].

PMID- 19585692
TI  - [The leaders of psychiatry and new steering ideals].

PMID- 19585694
TI  - The myths about long-term care.

PMID- 19585695
TI  - Comprehensive genomic analysis of cell wall genes in Aspergillus nidulans.
AB  - Knowledge of the mechanisms underlying cell wall biosynthesis in Aspergillus spp.
      is of high relevance to medicine and food safety, and for biotechnological
      applications. The cell wall of Aspergillus nidulans is composed of
      galactomannoproteins, 1,3-alpha-glucan, beta-glucans, and chitin. Here, we
      present a comprehensive inventory of the cell wall-related genes in A. nidulans.
      This includes glycan-synthetic and glycan-processing enzymes, spore wall
      maturation enzymes, GPI-anchor processing enzymes, GPI proteins and hydrophobins,
      and signaling proteins of the cell wall integrity pathway. All major known fungal
      cell wall-related genes are represented, except for Pir-CWPs. Importantly, we
      have identified a gene product that is possibly involved in the synthesis of
      1,3/1,4-beta-glucan, and we propose that four predicted GPI proteins, a mixed
      linked beta-glucanase and three amylase-like alpha-glucanases, may have
      transglucosidic activities pertaining to the processing of 1,3/1,4-beta-glucan
      and 1,3/1,4-alpha-glucan, respectively. We further present an updated survey of
      putative GPI proteins. Finally, we present mass spectrometric evidence suggesting
      the presence of at least twelve covalently-linked cell wall proteins in the
      hyphal wall of A. nidulans, including ten predicted GPI proteins, most of which
      belong to carbohydrate-active enzyme families that are also found in the walls of
      ascomycetous yeasts.

PMID- 19585696
TI  - Various possible positions of conventional catheters around the femoral nerve
      revealed by neurostimulation.
AB  - BACKGROUND AND OBJECTIVES: In continuous femoral nerve blocks, the various
      perineural positions of the tip of a conventional catheter and their clinical
      implication are not completely known.We used stimulating catheters to explore the
      relationship of catheter tip to nerve. METHODS: American Society of
      Anesthesiologists physical status IYII patients scheduled for total knee
      arthroplasty were administered effective single-shot blocks of the obturator and
      sciatic nerves using ropivacaine 0.5% 10 and 20 mL, respectively. Continuous
      femoral blocks were performed using stimulating catheters, which were advanced
      blindly. Neurostimulation via catheter was performed but was masked from the
      investigators' sight. Before general anesthesia was induced for surgery, 5 mL of
      ropivacaine 0.2% was administered through the femoral nerve catheter, followed by
      infusion (5 mL/hr). Visual analog scale (VAS) score at rest was recorded on
      admission to the postanesthesia care unit. Characteristics of neurostimulation
      via the catheters were analyzed. RESULTS: Thirty-three patients were studied.
      Motor responses to stimulation via the catheters were obtained at 1 mA or less in
      55% of patients and at greater than 1 mA in 45%. Various motor responses involved
      twitches of the pectineus (12%), sartorius (18%), or quadriceps (48%) muscles, or
      no muscular twitch up to 5 mA (22%). Catheter-induced motor response at 1 mA or
      less was associated with median values of VAS scores lower than those at greater
      than 1 mA (0 vs 30 mm; P = 0.008). CONCLUSION: The effectiveness of a continuous
      femoral block depends on neurostimulation characteristics, which likely
      correspond to various possible catheter tip positions. Conventional catheters
      provide no information on this issue. These results suggest that better VAS
      scores are attainable by placing catheters with neurostimulation guidance.

PMID- 19585698
TI  - E. Solowiej, J. Solowiej, M. Godlewski, et al. Regarding the article "Application
      of Sulforaphane: histopathological study of intraportal transplanted pancreatic
      islets into livers of diabetic rats," Transplant Proc (2006 Jan/Feb) 38(1): pages
      282-283.

PMID- 19585697
TI  - A randomized, observer-blinded determination of the median effective volume of
      local anesthetic required to anesthetize the sciatic nerve in the popliteal fossa
      for stimulating and nonstimulating perineural catheters.
AB  - BACKGROUND AND OBJECTIVES: Stimulating perineural catheters are developed to
      overcome technical problems of nonstimulating catheters, but their efficacy
      remains controversial. However, no volume-response study has compared success
      rates between stimulating and nonstimulating catheters. This study of stimulating
      versus nonstimulating catheters compares the minimal effective volume required to
      successfully block the sciatic nerve in 50% of patients scheduled for unilateral
      hallux valgus repair. METHODS: Patients underwent unilateral sciatic nerve block
      in the popliteal fossa with mepivacaine 1.5%, using either a stimulating (STIM
      group) or a nonstimulating (NONSTIM group) popliteal catheter. The volume of
      mepivacaine started at 20 mL and was increased or decreased by increments of 2 mL
      in subsequent patients, depending on the efficacy of the block in the previous
      patient, using the technique of up-down sequential allocation described by Dixon
      (Neurosci Biobehav Rev. 1991;15:47-50). Minimum effective volumes of local
      anesthetic were calculated using the formula of Dixon. Efficacy of block was
      defined by a complete sensory-motor block in the cutaneous distributions of the
      sciatic nerve associated with a pain-free surgery. RESULTS: Twenty-four patients
      were included in each group. Median effective volume blocking the sciatic nerve
      was significantly lower (P < 0.05) in the STIM group (2.7 mL; 95% confidence
      interval, 0.5-4.9 mL) compared with the NONSTIM group (16.6 mL; 95% confidence
      interval, 15.2-18.0 mL). CONCLUSION: Stimulating popliteal catheters dramatically
      decrease the volume required to block the sciatic nerve in 50% of patients,
      compared with nonstimulating catheters.

PMID- 19585699
TI  - Measurement of shift of the cauda equina in the subarachnoid space by changing
      position.
AB  - BACKGROUND AND OBJECTIVES: To perform spinal anesthesia, patients are usually
      placed in the lateral decubitus position with the knees drawn up to the stomach,
      the legs fully flexed, and the neck flexed to curve the back outward. Because the
      nerve roots of the cauda equina have considerable mobility in the subarachnoid
      space, the position of the cauda equina in the lateral decubitus position may be
      different from that in the supine position. However, the anatomic position of the
      cauda equina in the lateral decubitus position with fully flexed legs has not
      been carefully studied. In the present study, we geometrically measured the
      movement of the cauda equina in the subarachnoid space by changing positions,
      using magnetic resonance imaging (MRI). METHODS: After obtaining the approval of
      the hospital ethics committee and written informed consent, 12 healthy volunteers
      (age, 34 years [SD, 10 years]; height, 169 cm [SD, 9 cm]; weight, 65 kg [SD, 10
      kg]) were studied with MRI, and their positions were changed as follows: the
      supine position, lateral decubitus position without fully flexed legs, and
      lateral decubitus position with fully flexed legs. The movement of the central
      point of the spinal cord and cauda equina by changing position was evaluated.
      RESULTS: The spinal cord and cauda equina were observed in the gravity-dependent
      side of the subarachnoid space in each position. The movement to the gravity
      dependent side by changing position from the supine to the lateral decubitus
      position was significant (mean [SD] in millimeters: T11/12, 0.7 [0.4]; T12/L1,
      1.5 [0.9]; L1/L2, 3.0 [1.0]; L2/L3, 3.4 [1.0]; L3/L4, 2.7 [0.9]; L4/L5, 2.0
      [0.9]; L5/S1, 1.2 [0.7]; S1/S2, 0.5 [0.2]). The most obvious shift was observed
      at the L2/3 intervertebral space. The fully flexed legs significantly moved the
      spinal cord and cauda equina to the ventral side of the subarachnoid space and
      created a free space in the dorsal side. The movement to the ventral side by the
      fully flexed legs was significant (mean [SD] in millimeters: T11/12, 2.2 [1.0];
      T12/L1, 4.1 [1.5]; L1/L2, 6.1 [0.5]; L2/L3, 5.4 [0.9]; L3/L4, 5.1 [1.9]; L4/L5,
      4.4 [1.1]; L5/S1, 5.0 [0.9]; and S1/S2, 2.6 [0.9]). The most obvious shift was
      observed at the L1/2 intervertebral space. CONCLUSION: The present study using
      MRI showed dynamical movement of the spinal cord and cauda equina due to changing
      position. The most obvious movements by changing from supine to lateral decubitus
      position and fully flexed legs were observed at the L2/3 and L1/2 levels,
      respectively.

PMID- 19585700
TI  - An animal model of "syringe feel" during peripheral nerve block.
AB  - BACKGROUND: The perception of high resistance during injection of a local
      anesthetic during regional anesthesia may indicate intraneural injection.
      Anesthetists' ability to detect high resistance by "syringe feel" has been
      questioned in the past. The aim of our study was to investigate the anesthetist's
      ability to detect abnormal resistance to injection using an animal model.
      METHODS: We created a model using nerve, muscle, bone, and tendon tissue
      dissected from a sheep. Regional anesthesia needles of 21-gauge and 100 mm were
      placed into each of these tissues under direct vision, and 40 anesthetists were
      then asked to inject normal saline from a 20-mL syringe. They were unable to see
      the needle position. Once injected into all 4 tissues, they were asked to state
      which tissue they thought each was. RESULTS: Of the 40 anesthetists, 12 (30%)
      correctly identified the nerve. This was no better than chance (25%) and shows
      that the tested anesthetists were unable to correctly identify beyond chance what
      tissues they were injecting into. When those who did not practice regional
      anesthesia regularly (n = 7) were excluded, similar results were obtained. Ten
      (30%) of the 33 self-identified experienced regional anesthetists correctly
      identified the nerve. A score that measured the number of correctly identified
      tissues (score 1) was used to compare anesthetists on grade and level of
      experience. This showed that the more experienced anesthetists did better than
      the less experienced ones. CONCLUSION: Under the conditions of this study model,
      anesthetists were unable to correctly identify intraneural injection by syringe
      feel during simulated regional anesthesia.

PMID- 19585701
TI  - Ultrasound-guided lumbar medial branch block in obese patients: a
      fluoroscopically confirmed clinical feasibility study.
AB  - BACKGROUND AND OBJECTIVES: Obesity is a major risk factor for lower back pain.
      Fluoroscope-guided medial branch block is a common diagnostic tool in these
      patients. Although approach to the facet joint guided by ultrasound has been
      demonstrated successfully in lean patients, its success in obese patients is
      unknown.We therefore evaluated the success rate of real-time ultrasound approach
      in obese patients in a clinical feasibility study. METHODS: We performed a total
      of 84 medial branch blocks in 20 obese patients (body mass index, >30 kg/m2)
      using ultrasound. We studied the success rate, measured depth to the facet joint,
      and assessed radiation dose and pain relief. RESULTS: Our success rate was 62%
      (52/84 blocks) when using ultrasound to guide needle placement. The average
      distance from skin to target point at the transverse process was 76 mm (SD, 15
      mm). Skin-target depth was significantly different between L4 and L5 on both
      sides (P = 0.01). The needle advancement could not be tracked to the target. The
      verbal rating scale scores before, immediately after, and 24 hrs after the
      procedure were 7.1 (SD, 2.4), 4.3 (SD, 3.1), and 3.8 (SD, 2.7), respectively. The
      average radiation dose was 0.226 mGy/m2 (SD, 0.196 mGy/m2). CONCLUSION: Medial
      branch blocks in obese patients cannot be performed by ultrasound guidance
      exclusively.

PMID- 19585702
TI  - Retained intrathecal catheter fragment after spinal drain insertion.
AB  - BACKGROUND AND OBJECTIVES: The placement of lumbar spinal drains is being done
      with increasing frequency to facilitate high-risk surgical procedures. One risk
      associated with these procedures is catheter shearing, resulting in a retained
      foreign body in the intrathecal space. Unlike retained epidural fragments, there
      are no guidelines on the management of this complication. The purpose of this
      article was to synthesize the literature on this subject to come up with
      guidelines for preventing and managing this complication. METHODS: Case report
      and review of all published cases. RESULTS: Most cases of retained catheters are
      associated with difficulty inserting or advancing the catheter. Among those cases
      treated conservatively, approximately one third of patients developed symptoms.
      Factors that must be considered when weighing the decision to surgically remove
      the retained catheter include patient comorbidities and desires, size and
      location of the fragment, infectious risk, the presence of neurologic symptoms,
      and scheduled surgical procedure. CONCLUSIONS: A retained intrathecal catheter
      can be managed conservatively in certain contexts. Periodic follow-up visits,
      with or without repeat imaging, are recommended in these circumstances.

PMID- 19585703
TI  - Manufacturer defends organic premix diet.

PMID- 19585704
TI  - Boosting immunity to herpes zoster.

PMID- 19585705
TI  - Film quiz: carpometacarpal fracture dislocation.

PMID- 19585706
TI  - Wisdom in caring research.

PMID- 19585708
TI  - On building nursing knowledge.

PMID- 19585707
TI  - Entry and regulation: evidence from health care professions.
AB  - In many countries, pharmacies receive high regulated markups and are protected
      from competition through geographic entry restrictions. We develop an empirical
      entry model for pharmacies and physicians with two features: entry restrictions
      and strategic complementarities. We find that the entry restrictions have
      directly reduced the number of pharmacies by more than 50%, and also indirectly
      reduced the number of physicians by about 7%. A removal of the entry
      restrictions, combined with a reduction in the regulated markups, would generate
      a large shift in rents to consumers, without reducing the availability of
      pharmacies. The public interest motivation for the current regime therefore has
      no empirical support.

PMID- 19585709
TI  - All-optical on-chip bit memory based on ultra  high Q InGaAsP photonic crystal.
AB  - We demonstrate all-optical bit memory operation with photonic crystal (PhC)
      nanocavities based on an InGaAsP substrate with a band gap at a wavelength of
      about 1.3 microm. The optical bistability is based on a refractive index
      modulation caused by carrier-plasma dispersion. The operating energy required for
      switching is only 30 fJ, and the minimum optical bias power for bistability is 40
      microW, which is about one hundred times less than that required for laser based
      bistable memories.

PMID- 19585710
TI  - [Cardiac arrest with varenicline: a case report].

PMID- 19585711
TI  - [Neonatal methaemoglobinemia and metoclopramide: case report].

PMID- 19585712
TI  - Thalidomide: new indication. For elderly myeloma patients: some improvement in
      first-line treatment.
AB  - (1) First-line treatment with the melphalan-prednisone combination increases
      median overall survival time by at least 3 years in half of myeloma patients over
      65 years of age; (2) Thalidomide, an immunodepressant, is now approved in the
      European Union as an adjunct to this treatment in elderly myeloma patients; (3)
      Clinical evaluation is based on 5 trials. One unblinded controlled trial included
      447 patients. The addition of thalidomide to the melphalan-prednisone combination
      increased survival time by at least 1.5 years in half of the patients (median
      survival time: 51.6 months versus 33.2 months). Another trial in 255 patients
      that was published in detail showed an increase in progression-free survival, but
      did not show an overall survival advantage, after more than 3 years of follow-up.
      Three similar trials have been reported as conference abstracts. One trial showed
      a survival advantage of 1.5 years, but the other two did not. These 3 trials also
      showed an increase in progression-free survival; (4) Thalidomide has frequent and
      sometimes severe adverse effects, including neuropathy, venous thrombosis and
      pulmonary embolism, cutaneous disorders and bradycardia; (5) Thalidomide is
      highly teratogenic. As it enters semen, men who have partners of child-bearing
      age must use very effective methods of birth control; (6) In practice, provided
      treatment is closely monitored, thalidomide can be added to the melphalan
      prednisone combination as first-line treatment for myeloma patients over 65 years
      of age.

PMID- 19585713
TI  - Ambroxol lozenges: new drug. Sore throat: better to just suck on hard candy.
AB  - No more relief than from sucking on hard candy for what is a minor, short-lived
      condition, but lozenges can provoke some adverse effects.

PMID- 19585714
TI  - Duloxetine: new indication. In generalised anxiety too? No thanks! No tangible
      efficacy but numerous and sometimes severe adverse effects.

PMID- 19585716
TI  - Bosentan: new indication. Also too risky in mildly symptomatic pulmonary arterial
      hypertension. No proven tangible benefit in mildly symptomatic patients, and too
      many adverse effects.

PMID- 19585715
TI  - Ambrisentan: new drug. Too risky in mildly symptomatic pulmonary hypertension.
AB  - (1) In patients with mildly symptomatic pulmonary hypertension (stage III), there
      is no firm evidence that ambrisentan reduces mortality or slows disease
      progression. In contrast, ambrisentan has frequent and sometimes serious adverse
      effects; (2) In patients whose physical activity is markedly restricted by
      pulmonary hypertension, it is better to continue using bosentan, with which we
      have far more experience.

PMID- 19585717
TI  - Cilostazol: new drug. Intermittent claudication: too little efficacy, too many
      risks.
AB  - (1) Intermittent claudication is usually a sign of generalised vascular atheroma,
      with prognosis mainly depending on the degree of coronary and cerebral
      involvement. Treatment is based on smoking cessation and regular exercise.
      Vasodilators have a purely symptomatic effect, modest at best, in increasing
      walking distance; (2) Cilostazol, a phosphodiesterase III inhibitor, is licensed
      in France (after 20 years on the market in Japan) as a treatment intended to
      increase walking distance in patients with intermittent claudication; (3) A
      double-blind placebo-controlled trial in 1439 patients showed no reduction in
      mortality after 3 years of treatment; (4) Cilostazol has been compared with
      pentoxifylline, another vasodilator with uncertain efficacy, in 3 clinical
      trials. No tangible difference in efficacy was observed; (5) A meta-analysis of 7
      double-blind placebo-controlled trials in a total of 1579 patients showed that
      cilostazol increased the pain-free walking distance by about 30 metres and the
      maximum walking distance by about 50 metres; (6) There is some evidence that
      cilostazol causes a dose-dependent increase in mortality, although the data are
      not statistically significant. However, excess mortality has been documented with
      other phosphodiesterase III inhibitors, especially in patients with heart
      failure; (7) Cilostazol can provoke dose-dependent cardiac arrhythmias, and
      sometimes haemorrhage (due to its antiplatelet effect); (8) Cilostazol is
      extensively metabolised by cytochrome P450 isoenzymes CYP 3A4 and CYP 2C6,
      creating a high risk of pharmacokinetic interactions with other drugs and with
      food; (9) In practice, patients with intermittent claudication should not be
      given cilostazol; they should instead be prescribed an antiplatelet drug and
      encouraged to stop smoking and to exercise regularly.

PMID- 19585718
TI  - Sorafenib: new indication. For some patients with liver cancer.
AB  - In a trial involving patients with advanced-stage liver cancer but unimpaired
      hepatic function, sorafenib increased the median survival time by about 3 months
      in half of patients, but provoked frequent adverse effects.

PMID- 19585719
TI  - Alemtuzumab: new indication. First line treatment of chronic lymphocytic
      leukaemia: continue to use oral chlorambucil.
AB  - A trial comparing alemtuzumab versus chlorambucil showed no survival advantage,
      but complete remissions were about 20% more frequent (as with fludarabine).
      Serious adverse effects are more frequent and varied.

PMID- 19585720
TI  - Rimonabant: marketing authorization suspended... at last: withdrawal. Half
      measures.
AB  - Marketing authorization was granted for rimonabant on the basis of shaky data and
      despite poorly documented dangers. It took the EMEA 2 years to take action, by
      advising practitioners not to prescribe this drug.

PMID- 19585721
TI  - Human polyvalent immunoglobulin: new indication. Multifocal motor neuropathy:
      slightly more muscle strength. Improvement in muscle strength, but frequent
      hypersensitivity reactions.

PMID- 19585722
TI  - Febuxostat: new drug. Hyperuricaemia: risk of gout attacks.
AB  - (1) For patients with chronic symptomatic hyperuricaemia who fail to respond to a
      low purine diet, allopurinol is the standard drug used to prevent complications.
      This xanthine oxidase inhibitor can, in rare instances, cause severe skin
      reactions. Probenecid, a uricosuric agent, with which there is also long
      experience, is a second-line option; (2) Febuxostat, another xanthine oxidase
      inhibitor, is now authorized for the treatment of hyperuricaemia; (3) Two
      randomised double-blind trials in 762 and 1072 patients tested various doses of
      febuxostat compared with a standard dose of allopurinol (33 mg/day). Febuxostat
      normalised uric acid levels more frequently than allopurinol. However, overall,
      more patients suffered gout attacks with febuxostat than with allopurinol during
      the first two months of treatment, despite preventive measures (30-35% versus
      22%). Between 3 and 6 months of treatment neither drug reduced the incidence of
      gout attacks more effectively than placebo. After one year of treatment about two
      thirds of patients suffered gout attacks, with no difference between the
      febuxostat and allopurinol groups; (4) In these trials there were more premature
      treatment withdrawals with febuxostat than with allopurinol; (5) The adverse
      effects of febuxostat are poorly documented, especially cardiac, hepatic,
      haematological and thyroid disorders. In the short term, severe cardiac
      disorders, based on a composite endpoint, were 4 to 5 times more frequent with
      febuxostat than with allopurinol. Treatment withdrawals due to hepatic disorders
      were more frequent with febuxostat than with allopurinol (2.8% versus 0.4%). The
      relative frequency of severe cutaneous disorders with febuxostat and allopurinol
      is not known; (6) Clinical evaluation does not include any head-to-head trials of
      febuxostat versus probenecid; (7) In practice, patients with hyperuricaemia
      should continue to receive allopurinol as first-line treatment, and probenecid as
      second-line treatment if allopurinol is ineffective.

PMID- 19585723
TI  - Postmenopausal hormone therapy and breast cancer.
AB  - (1) According to the WHI trial, postmenopausal hormone replacement therapy
      exposes women to an additional risk of breast cancer of about 8 cases a year per
      10 000 treated women; (2) In the United States, a comparison of the breast cancer
      incidence rates in 2001 and 2004 showed an overall annual decrease of 8.6%,
      attributable to the reduction in the use of hormone replacement therapy in
      postmenopausal women. A similar phenomenon was observed in France, Germany and
      Canada; (3) In summary, if prescribers had waited for the results of the WHI
      trial, many cases of breast cancer would probably have been avoided.

PMID- 19585724
TI  - Drug-induced hypoglycaemia.

PMID- 19585725
TI  - Topical becaplermin: cancer. Think twice before using it.

PMID- 19585726
TI  - Sorafenib: gastrointestinal perforation. Known reactions to VEGF inhibitors.

PMID- 19585727
TI  - Drug-eluting coronary stents: many meta-analyses, little benefit.
AB  - (1) Angioplasty is one method of unblocking a stenosed coronary artery. A metal
      stent is sometimes placed in the vessel lumen. Drug-eluting stents coated with an
      immunosuppressant or cytotoxic drug have been developed with the objective of
      reducing the risk of recurrent stenosis; (2) We examined the available literature
      on the efficacy and adverse effects of drug-eluting stents, based on the standard
      Prescrire methodology; (3) We found a plethora of clinical trials of drug-eluting
      stents, and numerous meta-analyses, reflecting the broad economic implications of
      the market for these devices. Yet drug-eluting stents appear to be no more
      effective than bare metal stents in reducing overall morality, cardiac mortality,
      the risk of myocardial infarction, or stent thrombosis. Few follow-up data are
      available beyond 4 years; (4) Revascularisation of the treated coronary artery
      was about half as frequent with drug-eluting stents as with bare metal stents.
      However, the apparent advantage is difficult to quantify because in some trials
      the decision to re-operate was based solely on angiographic criteria, leading to
      more frequent revascularization. Sirolimus-eluting stents appear to be slightly
      more effective than paclitaxel-eluting stents in terms of the revascularisation
      rate; (5) In contrast, late thrombosis (more than a year after stent placement)
      seems to be more frequent with drug-eluting stents than with bare metal stents.
      This risk can be reduced by long-term antiplatelet treatment (with clopidogrel
      plus aspirin), but the benefit is offset by the accompanying increased risk of
      severe haemorrhagic events. Serious allergic reactions have also been reported;
      (6) In most cases, especially when the risk of restenosis is low or moderate, it
      is better to use a bare metal stent. Coronary artery bypass grafting should be
      considered when there is a high risk of restenosis. Drug-eluting stents are just
      one alternative to surgery.

PMID- 19585729
TI  - Pacific mental health and addictions.

PMID- 19585728
TI  - Irritable bowel syndrome: a mild disorder; purely symptomatic treatment.
AB  - (1) Patients frequently complain of occasional bowel movement disorders,
      associated with abdominal pain or discomfort, but they are rarely due to an
      underlying organ involvement. Even when patients have recurrent symptoms, serious
      disorders are no more frequent in these patients than in the general population,
      unless other manifestations, anaemia, or an inflammatory syndrome is also
      present; (2) There is currently no way of radically modifying the natural course
      of recurrent irritable bowel syndrome; (3) The effects of antispasmodics on
      abdominal pain have been tested in about 20 randomised controlled trials.
      Pinaverium and peppermint essential oil have the best-documented efficacy and
      only moderate adverse effects. Antispasmodics with marked atropinic effects do
      not have a favourable risk-benefit balance; (4) Tricylic antidepressants seem to
      have only modest analgesic effects in this setting. In contrast, their adverse
      effects are frequent and they have somewhat negative risk-benefit balances. Nor
      has the efficacy of selective serotonin reuptake inhibitor antidepressants
      (SSRIs) been demonstrated; (5) Alosetron and tegaserod carry a risk of
      potentially life-threatening adverse effects and therefore have negative risk
      benefit balances; (6) Seeds of plants such as psyllium and ispaghul, as well as
      raw apples and pears, have a limited impact on constipation and pain. Osmotic
      laxatives are effective on constipation. Symptomatic treatments for constipation
      can sometimes aggravate abdominal discomfort; (7) Loperamide has been poorly
      assessed in patients with recurrent irritable bowel syndrome with diarrhoea. It
      modestly slows bowel movement but does not relieve pain or abdominal discomfort;
      (8) Dietary measures have not been tested in comparative trials. Some patients
      are convinced that certain foods provoke a recurrence of irritable bowel
      syndrome, but restrictive diets carry a risk of nutritional deficiencies; (9)
      Various techniques intended to control emotional and psychological disturbances
      have been proposed, including relaxation, biofeedback, hypnosis, and
      psychotherapy. The results of clinical trials are not convincing; (10) Oral
      products containing live bacteria, designed to change the equilibrium of
      intestinal flora, have been tested in 13 placebo-controlled trials, with
      inconsistent results. A few cases of septicaemia have been reported; (11) The six
      available trials of acupuncture (versus sham acupuncture) showed no more than a
      placebo effect; (12) In practice, patients who have recurrent irritable bowel
      syndrome but with no other signs of a condition warranting specific treatment
      should be reassured as to the harmless nature of their disorder if a careful
      physical examination and basic laboratory tests are negative. The only available
      treatments have purely symptomatic effects and only limited efficacy. It is best
      to avoid using all treatments and additional diagnostic investigations that carry
      a risk of disproportionate adverse effects.

PMID- 19585730
TI  - Twelve-month prevalence, severity, and treatment contact of mental disorders in
      New Zealand born and migrant Pacific participants in Te Rau Hinengaro: The New
      Zealand Mental Health Survey.
AB  - OBJECTIVE: To investigate differences in 12-month prevalences of mental disorders
      and 12-month treatment contact among New Zealand born and migrants in separate
      ethnic groups in Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS).
      DATA: The NZMHS is a nationally representative face-to-face household survey,
      carried out in 2003-2004 with a response rate of 73.3%. It surveyed 12,992 New
      Zealand adults aged 16 and over Pacific people were over sampled This paper
      focuses on the 2374 Pacific participants but includes for comparison 8160 non
      Maori-non-Pacific participants (Others). METHOD: Multiple logistic regression
      models were used to produce estimates weighted to account for diferent
      probabilities of selection and taking account of the complex survey design.
      RESULTS: The prevalence of mental disorder was lowest among those who migrated as
      adults compared with those who migrated as young children (child migrants) or New
      Zealand-born (NZ born) migrant descendants in both Pacific and other ethnic
      groups. While Pacific people have higher rates of disorder than Others, many of
      the observed differences between Pacific and Others were explained by population
      differences in age and sex. Service use in the last 12 months by people with a
      disorder was low among Pacific peoples overall, but spec fically among older
      migrants. Older Pacific migrants with a disorder had particularly low use of
      specialist mental health services. CONCLUSION: An interesting picture has emerged
      regarding need for and use of mental health services. The burden of mental
      disorder is highest while service use was lower among Pacflc peoples generally
      Those born in or who migrated as children to New Zealand had higher levels of
      disorder but were also more likely to use services than older migrants.

PMID- 19585731
TI  - Exploration of Pacific perspectives of Pacific models of mental health service
      delivery in New Zealand.
AB  - There is increasing concern about the inequalities, overall health outcomes, and
      mental health of Pacific peoples residing in New Zealand. The New Zealand Mental
      Health Survey (Te Rau Hinengaro), conducted in 2003/2004, identfied Pacific
      peoples as having a higher 12-month prevalence of mental disorders than the
      general population. The burden of mental health amongst Paqfic peoples was
      identified as high and associated with other socioeconomic correlates.
      Pacflcpeoples were also more likely not to access professional mental health
      assistance. The aim of this study was to provide indepth qualitative data that
      explored Pacflc perceptions and experience of the theory practice, and
      utilisation of Pacific mental health services in New Zealand This paper
      documents: (i) the different models of care practiced in the Pacific mental
      health sector and (ii) the specific components that: (a) make these models
      uniquely Pacific, and (b) that consumers and families identWed as integral to the
      recovery process. Pacific peoples 'views of mental health from the following
      three perspectives were studied: (i) the service provider (ii) the mental health
      consumer and (iii) the family member, using focus group interviews in Auckland,
      Hamilton, Wellington, and Christchurch. The results report the different
      perceptions of the Pacific focus group and interview participants. Our findings
      indicate that firstly, having appropriate family and community support networks
      (psycho-social and community), appropriate living environments and meaningful
      workfor consumers, and secondly, access to culturally competent mental health
      staff contributes towards consumer recovery and assisting families. In
      conclusion, Pacific models of care (service delivery) were found to be informed
      by Pacific models of health belief and existed in implicit rather than explicit
      forms. To develop clearer or specific articulations of Pacific models of service
      delivery, the first step for services is to develop written expositions (a
      theory) of how these models might be framed taking into equal account cultural,
      clinical, and service management issues.

PMID- 19585732
TI  - Community rehabilitation outcomes across cultures following traumatic brain
      injury.
AB  - OBJECTIVE: This exploratory study investigates Traumatic Brain Injury (TBI)
      rehabilitation outcomes among culturally diverse outpatients in community-based
      rehabilitation who have sustained a Mild to Moderate TBI. The major aims of this
      study are twofold: firstly, to determine whether community-based rehabilitation
      outcomes following TBI differ across Maori, Pacific and Pakeha cultures; and
      secondly, to identify any service delivery needs Pacific people in TBI
      rehabilitation require that may be distinct from Pakeha. METHOD: A fixed
      comparative non-experimental design was utilised where participants were selected
      using direct control based on their self-identified ethnic group resulting in sub
      samples of 11 Maori, 11 Pacific and 11 Pakeha (n=33). Each participant completed
      the Neurobehavioural Cognitive Status Examination (Cognistat) and the Brain
      Injury Community Rehabilitation Outcome Scales (BICRO-39 Scales). RESULTS:
      Results indicate that all participants were at a similar level of overall
      cognitive functioning but Pacific peoples scored significantly lower than both
      Maori and Pakeha on two Language subtests and significantly lower than Pakeha on
      the Memory subtest. Individual handicap increased following TBI and decreased
      following rehabilitation, with no significant difference across cultures and
      suggesting good efficacy of rehabilitation. CONCLUSION: There appears to be
      universalities in TBI experience and global rehabilitation outcomes that
      transcends individual cultures. However; there are micro-level cultural
      variations that have valuable implications when assessing and treating Pacific
      people in neuro-rehabilitation. Neuropsychologists need to take into account
      formal education levels and language abilities when working with Pacific people.

PMID- 19585733
TI  - Child discipline and nurturing practices among a cohort of Pacific mothers living
      in New Zealand.
AB  - The Pacific Islands Families (PIF) study is a longitudinal investigation of a
      cohort (N=1376) of Pacific infants born in New Zealand (NZ), and their mothers
      and fathers. OBJECTIVES: The PIF study aimed to determine: (1) the prevalence of
      disciplinary and nurturing parenting practices used with children at 12 months of
      age, and (2) the demographic, maternal and lifestyle factors associated with
      parenting practices. METHODS: At the 12-month measurement point, mothers (N=1207)
      were interviewed about their parenting practices using a modified version of the
      Parent Behaviour Checklist. RESULTS: High nurturance was significantly associated
      with Samoan ethnicity and post school qualifications, and low nurturance was
      significantly associated with post-natal depression, alcohol consumption and
      gambling. At the univariate level, high discipline scores were significantly
      associated with gambling, postnatal depression and lack of alignment to either
      Pacific or to European traditions. However the strongest association with
      discipline was the ethnicity variable with Tongan mothers reporting significantly
      higher disciplinary behaviours that all other ethnicities. CONCLUSIONS: It is
      clear that there are a number of common underlying lifestyle issues that need to
      be considered when dealing with parenting problems in families with young
      children. However specific to Pacific families, is Tongan ethnicity accounting
      for a strong cultural effect on parenting style, in particular high discipline
      scores relative to other Pacific groups. This important finding may be used to
      guide social policy and prevention programmes that are focused on the wellbeing
      of Pacific mothers and their children.

PMID- 19585735
TI  - Two years on: gambling amongst Pacific mothers living in New Zealand.
AB  - Research investigating the prevalence and correlates of Pacific peoples gambling
      within a New Zealand context is limited. This paper provides data about gambling
      activity from the two-year data collection point for a cohort of mothers within
      the longitudinal Pacific Islands Families study. The results indicate a number of
      consistencies and discrepancies between data collected at this time point and two
      years previously (six-week baseline data collection point). For example, at
      baseline, Samoans were the least likely to gamble and spent less money on
      gambling activities. Two years later, Samoans remained the least likely to
      gamble, but those who did gamble, were more likely to spend more money than other
      ethnicities. This article highlights the importance of this type of prospective
      study in examining the development of the risk and protective factors in relation
      to the development of problem gambling.

PMID- 19585734
TI  - 'From Kava to Lager'--alcohol consumption and drinking patterns for older adults
      of Pacific ethnic groups, and Europeans in the Diabetes Heart and Health Study
      (DHAHS) 2002-2003, Auckland New Zealand.
AB  - AIM: This paper describes and compares alcohol consumption and drinking patterns
      for Pacific ethnic groups (Samoan, Tongan, Niue, Cook Islands) and European New
      Zealanders by gender participating in the 2002-03 Diabetes Heart and Health Study
      (DHAHS). METHODS: The DHAHS was a cross-sectional population based study of
      people age 35-74 years carried out in Auckland between 2002-03. A total of 1011
      Pacific people comprising of 484 Samoan, 252 Tongan, 109 Niuean, 116 Cook
      Islanders and 47 'Other Pacific' (mainly Fijian) and 1745 European participants
      took part in the survey Participants answered a self-administered questionnaire
      to assess whether they consumed alcohol, their drinking patterns and consumption
      levels and reasons for stopping drinking. RESULTS: Approximately half (51.3%) of
      all Pacific people did not currently drink compared to 6.2% of the European
      population. Of 'non-drinkers'--never Drinking'was significantly more common in
      Pacific (40%) compared to Europeans (13%) p < 0.0001. Ex-drinkers comprised 6.3%
      of the 'ever-drank' population for European compared to 27.6% for Pacific. The
      majority of Pacific men and women drinkers (>60%) consumed alcohol 'weekly' or
      'less than weekly'. In contrast the majority of European men and women drinkers
      (>60%) consumed alcohol '2-3 days per week' or 'daily'. European men were
      significantly more likely to drink wine and spirits, and European women were
      significantly more likely to drink wine than their Pacific counterparts. Pacific
      drinkers consumed an average of 6.9 drinks on a typical occasion and 82 mls of
      pure alcohol per week, compared to 3.6 drinks and 126 mls per week for Europeans.
      CONCLUSION: Middle-aged and older Pacific adults are less likely to consume
      alcohol than Europeans however those who drink consume more on a typical occasion
      but drink less regularly resulting in lower weekly consumption of pure alcohol.
      Drinking patterns in these Pacific adults tend to show substantial diversity by
      age (older are less likely to drink), sex (women less likely to drink), and
      financial deprivation (middle groups consume more than least and most financially
      deprived). For Europeans a more homogenous drinking style prevailed by age, sex,
      and deprivation. Pacific drinkers were also approximately five times more likely
      to stop drinking compared to Europeans, citing family and social reasons as their
      main motivation for stopping drinking.

PMID- 19585736
TI  - Mental health well-being amongst fathers within the Pacific Island Families
      Study.
AB  - This article investigates the prevalence of potential psychological disorder
      amongst a cohort of primarily Pacific fathers in New Zealand over their child's
      first 6-years of life. The analysis is based on data collected at 12-months, 2
      years and 6-years postpartum during the Pacific Islands Families Study, and uses
      the 12-item General Health Questionnaire (GHQ12) to assess the prevalence of
      psychological distress amongst participant fathers at each measurement wave.
      Various sociodemographic and potentially confounding variables were also
      investigated to determine their effect on the risk of developing potential mental
      health disorder. The majority of fathers within the study reported good overall
      health and well-being and their prevalence of 'symptomatic' disorder was
      initially low at 12-months (3.90%) but increased significantly at 2-years (6.6%)
      and at 6-years (9.80%) in crude and adjusted analyses (both P-values < 0.001). In
      the adjusted analysis, the odds of symptomatic cases at 2-years was 1.7 (95%
      confidence interval: 1.1, 2.8) times that observed at 12-months postpartum and at
      6-years the odds was 3.2 (95% confidence interval: 1.9, 5.2) times that observed
      at 12-months. Moreover in the adjusted analysis, smoking status, marital status,
      employment status, and ethnicity, were all significantly associated with the risk
      of developing symptomatic mental health disorder

PMID- 19585737
TI  - Twelve-month prevalences of mental disorders and treatment contact among Cook
      Islanders resident in New Zealand.
AB  - OBJECTIVE: To show the 12 month prevalences of mental disorders, 12-month
      treatment contact and use of mental health services among Cook islanders resident
      in New Zealand. DATA: (A) The New Zealand Mental Health Survey (NZMHS) is a
      nationally representative face-to-face household survey, carried out in 2003
      2004. It surveyed 12,992 New Zealand adults aged 16 or more including 2374 Pacflc
      peoples (500 Cook Islands Maori) and 2457 New Zealand Maori. (B) An extract from
      the Mental Health Information National Collection (MHINC). This is a national
      dataset that is reported to by mental health services around New Zealand. METHOD:
      Multiple logistic regression models are used to produce estimates from both sets
      of data. In the case of A) the NZMHS the results are weighted to account for
      different probabilities of selection and analysis takes account of the complex
      survey design. RESULTS: A previous paper and this one confirm that Cook Islanders
      experience high prevalence of mental disorders. However the difference is more
      attributable to their population age and gender structure or being New Zealand
      born than from ethnicity. The prevalence was higher among New Zealand-born Cook
      Islanders than those born in the Cook Islands. Those born in the Islands with a
      disorder were less likely to have used a health service for their mental health
      compared with others and much less likely to have visited a specialist mental
      health service. From MHINC, twelve month data on use of mental health services
      shows: high use of acute inpatient and Forensic mental health services by Cook
      Island clients but similar levels of community mental health services. Cook
      Islands clients were more commonly diagnosed with bipolar psychotic or
      schizophrenic disorders. They were also more likely to be diagnosed with a
      substance disorder. CONCLUSION: In spfte of high levels of disorder Cook
      Islanders have low use of specialist mental health services. The exception to
      this is an over-representation in inpatient and forensic services. This
      experience of mental health services at the extreme end implies delayed or
      avoided treatment that has resulted in more serious levels of disorder among
      those Cook Islanders who are eventually seen by mental health services.

PMID- 19585738
TI  - Walking apart but towards the same goal? The view and practices of Tongan
      traditional healers and western-trained Tongan mental health staff.
AB  - This study explored the mental health-related beliefs and practices of Tongan
      Traditional Healers and Tongan workers in the Western-style mental health
      services in Tonga. The groups showed very different explanatory models and
      treatment methods for mental health difficulties. A variety of methods, similar
      to those reported in other Pacific communities, were used by the Tongan
      Traditional Healers. The Traditional Healers had a negative view of the Western
      style system, feeling it did not address the real issues in mental health that
      they considered more culturally and spiritually-based. Western-trained staff were
      generally more accepting of traditional healing, and incorporated aspects of
      Tongan culture into their practice, but did not typically include traditional
      healing practices. This study aimed to inform efforts to foster more synergy and
      collaboration between traditional and western healing approaches in Tonga and
      with Tongans elsewhere. The results may be relevant to other Pacific peoples.

PMID- 19585739
TI  - The social, cultural and medicinal use of kava for twelve Tongan born men living
      in Auckland, New Zealand.
AB  - Kava consumption is a very popular practise amongst Pacific people especially
      amongst the Tongan communities. The purpose of this paper is to identify some of
      the key cultural, social and medicinal elements of kava use amongst Tongan men.
      Twelve face to face interviews in this study were undertaken. The paper argues
      that kava drinking is strongly linked to many of the ceremonial, social and
      cultural obligations that are deeply embedded within the Tongan culture. The
      positive uses of kava include medicinal purposes, male bonding, alternative to
      alcohol consumption, reaffirming and establishing relationships amongst other
      Tongan men, The men also stated negative uses of kava such as it made them lazy,
      tired so they were not able to go to work, a lack of sexual activities by being
      too tired have sex with their partners, and very expensive to buy in New Zealand.
      AIM: The aim of this paper is to discuss and examine the social, cultural and
      medicinal kava use amongst twelve Tongan born men living in Auckland, New
      Zealand. METHODS: The study used qualitative methods, specifically individual
      interviews were conducted in Tongan or English. Participants were recruited
      through community networks in Auckland. A number of Tongan churches, Tongan
      medical clinics such as Langimailie, and kava clubs were approached to recruit
      participants. The open ended interview schedule covered themes such as access,
      quantity, frequency, and problems associated with kava use. The interviews were
      conducted by a Tongan researcher either in English or Tongan. All interviews were
      translated and transcribed into English. A thematic analysis based on multiple
      readings of the transcripts was used The analysis identified commonalities and
      differences. The study was granted ethical approval by the University of Auckland
      Human Subjects Ethics Committee in December 2004. Interviews were conducted at
      the beginning of 2005. Interviews were undertaken in a place where the
      participants felt comfortable. Interview times were arranged at a time convenient
      for the participants. All participants were given information sheets prior to
      interviews, and participants were asked to sign consent forms before the
      interviews commenced. These forms were provided in Tongan and English versions.
      Most of the interviews ranged between one to three hours. Interviews were
      audiotaped, and confidentiality was maintained throughout the research.
      PARTICIPANTS: Twelve men were interviewed. All participants were Tongan men born
      and raised in Tonga. The ages of men ranged between 30 and 75 years. Most of the
      men had been residing in New Zealand for over 30 years, although some men had
      only been in New Zealand between 2-18 years. Most of the men were employed and a
      few had retired from work. Most of these men also belonged to a church. All of
      the men who participated were married.

PMID- 19585741
TI  - The interface between cultural understandings: negotiating new spaces for Pacific
      mental health.
AB  - This theoretical paper introduces the concept of the "negotiated space", a model
      developed by Linda Tuhiwai Smith, Maui Hudson and colleagues describing the
      interface between different worldviews and knowledge systems. This is primarily a
      conceptual space of intersection in-between different ways of knowing and meaning
      making, such as, the i Pacific indigenous reference and the dominant Western
      mental health paradigm of the bio-psycho-social. When developing Pacific models
      of care, the "negotiated space" provides room to explore the relationship between
      different (and often conflicting) cultural understandings of mental health and
      illness. The "negotiated space" is a place ofp urposive re-encounter
      reconstructing and re-balancing of ideas and values in complementary realignments
      that have resonance for Pacific peoples living in Western oriented societies.
      This requires making explicit the competing epistemologies of the Pacific
      indigenous worldviews and references alongside the bio-psycho-social and
      identifying the assumptions implicit in the operating logic ofe ach. This is a
      precursor to being empowered to negotiate, resolve and better comprehend the
      cultural conflict between the different understandings. This article theorises
      multiple patterns of possibility of resolutions and relationships within the
      negotiated space relevant to research, evaluation, model, service development and
      quality assurance within Pacific mental health.

PMID- 19585740
TI  - Tau Fifine Fiafia: the binge drinking behaviours of nine New Zealand born Niuean
      women living in Auckland.
AB  - The aim of this paper is to explore the binge drinking behaviours and attitudes
      of nine New Zealand born Niuean women aged 18 to 45 plus years living in Auckland
      who are heavy binge drinkers. Taped interviews were conducted individually with
      nine Niuean participants, utilising a semi-structured interviewing schedule in
      both Niuean and English languages. This study argues that excessive drinking
      style of binge drinking commonly practised with the younger generation of Niuean
      women. The study highlighted the important role of supportive friends and women
      within a drinking circle compared to the cultural and gender restrictions when
      drinking with males. NZ born Niuean women outlined there were fewer limitations
      on alcohol use and behaviour associated with drunkenness; the reason for drinking
      was to reach a level of intoxication. Alcohol consumption was seen as a way of
      socialising, having fun, being happy and feeling safe primarily when drinking
      with other women, even though participants experienced negative behaviour when
      safety was threatened. The Niuean community needs to address alcohol related
      issues affecting Niuean women through education awareness within social and
      cultural gatherings. This study is not a representative study and it cannot be
      generalised to all New Zealand born Niuean women because the sampling size is too
      small. AIM: The aim of this paper is to look at the binge drinking behaviours of
      nine New Zealand born Niuean women living in Auckland. METHODS: A qualitative
      research methodology offace to face interviews was used to interview NZ born
      Niuean women and their alcohol consumption. Participants were recruited by using
      a snow ball methodology. Participants were also approached throughout the
      community on the telephone and via email/internet about the research.
      Participants were also from Niuean gatherings such as Niuean cultural workshops,
      weaving groups, church groups, and sports groups, Niuean websites. A semi
      structured interview format was used making it more informal and comfortable for
      the participant by using open ended questions. These questions include first
      drinking experiences, reasons for drinking, drinking styles, drinking venues and
      environments, times to drink, risky behaviours and attitudes, pregnancy and
      sexual behaviours. The interviews ranged from 1-2 hours. Ethical approval for the
      research was obtained from the University of Auckland Human Participants Ethics
      Committee in June 2004. Interviews were done in Niuean or English optional for
      the participants in the study. An important feature of the research process and
      cultural appropriateness is that I am New Zealand born but was raised in Niue
      Island as a young child. I am fluent in both English and Niuean languages. My
      Niuean cultural back ground and knowledge will be beneficial in the formulation
      of ideas and interpretations in the interview discussions and research data
      analysis. The researcher will interpret the cultural knowledge and understanding
      throughout the discussions which will be useful when gathering and analysing
      empirical information gathered from the research. PARTICIPANTS: There were nine
      New Zealand born Niuean women aged between 18-45yrs plus living in Auckland who
      participated. Two of the participants are half palagi (European) and half Niuean.
      This is a reflection of the young population that many Niuean women today are
      born into in New Zealand, as the majority of Niues population is New Zealand
      born. The NZ born young women views were highlighted in this study because of the
      growing population of Niue communities in Auckland, New Zealand. The participants
      were from diverse backgrounds, from professional career minded women,
      beneficiaries, single, married, mothers, solo parent, tertiary students.

PMID- 19585742
TI  - Exploring the 'cultural' in cultural competencies in Pacific mental health.
AB  - Cultural competency is about the ability of individuals and systems to respond
      respectfully and effectively to the cultural needs of peoples of all cultures.
      Its general attributes include knowledge, attitudes, skills and professional
      judgment. In Pacific mental health, 'the cultural' is generally understood to be
      ethnic culture. Accordingly, Pacific cultural competencies assume ethnic specific
      markers. In mental health Pacific cultural competencies has seen a blending of
      cultural and clinical beliefs and practices. This paper provides an overview of
      five key theme areas arising from Auckland-based ethnic-specific Pacific workshop
      data: language, family, tapu relationships, skills and organisation policy.
      Workshop participants comprised of Pacific mental health providers, Pacific
      consumers, family members of Pacific consumers and members of the Pacific
      community members. This paper purports that identifying the perceptions of
      different Pacific groups on ethnic-specific elements of cultural competencies are
      necessary to build and strengthen the capacity and capability of mental health
      services to provide culturally relevant services.

PMID- 19585743
TI  - Development of a mental health and addiction Pacific cultural practice framework
      for the Auckland region: promoting expertise that is "visible, valued and
      understood".

PMID- 19585744
TI  - Development of a child, adolescent and family mental health service for Pacific
      young people in Aotearoa/New Zealand.
AB  - This paper describes the development of a dedicated Pacific child, adolescent and
      family mental health service based in Porirua, Aotearoa/New Zealand (NZ).
      Particular reference is made to, firstly, the social and demographic
      characteristics of the population we serve, and referrals to our service, and
      secondly, to key Samoan research findings which emphasize the Samoan relational
      concept of self as a fundamental concept underpinning Samoan notions of mental
      wellbeing'. We discuss the practical application of this concept in our work with
      Samoan and other Pacific young people and their families, including implications
      for engagement, assessment and treatment processes.

PMID- 19585745
TI  - A Samoan perspective on infant mental health.
AB  - This paper describes background to the development of the relatively new field of
      infant mental health and why this may be important for Pacific communities in
      Aotearoa/New Zealand (NZ) and elsewhere. There is a discussion of Samoan concepts
      and research that could inform infant mental health theory and practice. A
      Pacific home visiting programme based at Taeaomanino Trust in Porirua,
      Aotearoa/NZ has formed a collaboration with child and adolescent mental health
      service clinicians with an interest in infant mental health, to further develop
      infant mental health understandings and practices in this early intervention
      service. The benefits and practical application of this collaboration are
      discussed. The paper ends with a personal perspective from one of the authors on
      her Samoan reflection on the relevance of attachment ideas to her family
      relationships and work with Pacific infants, mothers and their families.

PMID- 19585746
TI  - Te Vaka Atafaga: a Tokelau assessment model for supporting holistic mental health
      practice with Tokelau people in Aotearoa, New Zealand.
AB  - Despite the emergence of dedicated Pacific mental health services in Aotearoa,
      New Zealand in the last 10 years, there have been few published Pacific models of
      mental health assessment to guide clinicians working with Pacific clients and
      their families. Te Vaka Atafaga is a Tokelau model consisting of 6 core concepts
      which are considered key aspects of health for Tokelau people. This model was
      endorsed by Tokelau community representatives and leaders at the Inaugural
      Tokelau Health National Conference held in Wellington New Zealand in 1992. The
      author relates the personal and professional journey that he has taken 'aboard'
      Te Vaka Atafaga over a twenty year period from conceptualisation, development and
      through to application in clinical practice in a mental health setting in
      Aotearoa, New Zealand.

PMID- 19585747
TI  - The Popao model: a Pacific recovery and strength concept in mental health.

PMID- 19585748
TI  - Reflections of a practitioner: purely a journey of the heart.
AB  - 32 years ago a man from the villages of Manunu (Upolu) and Fagamalo (Savai'i) and
      a woman from the inner-town village of Matautu tai-Apia (Upolu) gave birth to
      their middle child and only daughter Siautu Tiomai Alefaio. The man left a
      prominent position in the police department's CIB in Samoa to become a factory
      worker in Hellaby Meats of Mt. Wellington, New Zealand. The woman, a beautiful
      dancer in Aggie Grey's dance troupe and also an upcoming photographer at the age
      of 12, left all her aspirations of education to attain a job in order to make
      enough money for the prospective dream of 'making it big' in the 'land free
      flowing with milk and honey'--Aotearoa New Zealand. For some years Aotearoa was
      exactly that, with money enough to bring over all their other siblings and
      eventually their mothers. My father (now a Parish minister of a Presbyterian
      church) and mother (an Early-Childhood educator) both self-sacrificially gave up
      their own hopes and dreams to pursue a bigger one--of prosperity for future
      generations. As a registered psychologist I have seen many journey stories
      similar to mine, and it is my own hope and dream that our contribution as people
      from "Le Vasa Pasefika" (vast ocean of the Pacific region) will inevitably pave
      the way for future generations to embrace all that they are and become all that
      they have been called to be.

PMID- 19585749
TI  - Mental health in the Pacific: the role of the Pacific Island Mental Health
      Network.
AB  - This article summarises the work being undertaken by the World Health
      Organisation Pacific Islands Mental Health Network (PIMHnet) since its inception
      in 2006. The article also outlines the mental health issues that present
      particular challenges in the Pacific region, and the innovative approaches that
      have been taken to address those issues, with the goal of improving mental health
      throughout the Pacific. PIMHnet is co-ordinated by Dr. Michelle Funk (Coordinator
      Mental Health Policy and Service Development Department of Mental Health and
      Substance Abuse WHO); Dr Xiangdong Wang (Regional Mental Health Advisor, WHO
      Regional Office for the Western Pacific); Dr. Frances Hughes (Facilitator PIMHnet
      and Stephanie Calder (Senior Analyst, PIMHnet).

PMID- 19585750
TI  - HDL-C as a new paradigm in atherosclerotic diseases.

PMID- 19585751
TI  - Dietary spices in health and diseases (II).
AB  - Dietary spices influence various systems in the body such as gastrointestinal,
      cardiovascular, reproductive and nervous systems resulting in diverse metabolic
      and physiologic actions. As inheritors of a long tradition of the use of spices
      in diet as well as in indigenous medicines we know that these are treatments
      often honed over centuries with well-established reputations for efficacy. A
      rigorous review of these manifold beneficial effects may provide a fair basis for
      prescription in many clinical conditions where confirmed modern drug treatments
      do not exist or as adjunct therapy to reduce the dosage or the, risk of side
      effects. This essay attempts to adjudicate the traditional use of dietary spices
      based on factual research evidence for their multivalent actions as health
      promoting dietary additives as well as putative therapeutic agents.

PMID- 19585753
TI  - 4-aminopyridine-induced contracture in frog ventricle is due to calcium released
      from intracellular stores.
AB  - The aim of the study is to demonstrate the presence of intracellular calcium
      store in frog ventricle based on contractures induced by 4-aminopyridine in
      calcium-free media. Frog-ventricular strips were subjected to field stimulation
      at 0.2 Hz and the force of contraction was recorded after stabilization. The
      preparation was then kept quiescent for some time in solutions with different
      sodium concentrations, containing 0 or 1 mmol/L calcium. Caffeine, 4
      aminopyridine (4-AP), or tetraethylammonium chloride was then added. Frog
      skeletal muscle preparations were used as positive controls for the caffeine
      experiments. Frog ventricular preparations did not develop contractures
      (sustained contractions) in the presence of caffeine (25 mmol/L), while frog
      skeletal muscle preparations developed caffeine-induced contractures. However, 4
      AP (16 mmol/L) was able to induce contractures in quiescent frog ventricular
      preparations, even when they were superfused with calcium-free solution. 4-AP
      contractures in frog ventricle were seen in the presence of nifedipine also.
      Amplitude of 4-AP evoked contractures in frog ventricle were much larger in low
      sodium (30 mmol/L) and sodium-free (sodium substituted by lithium) solutions than
      in normal sodium solution, suggesting that the route of extrusion of the
      cytosolic calcium (released from intracellular stores by 4-AP) is the sodium
      calcium exchanger, which gets reversed in low sodium solutions.
      Tetraethylammonium chloride (TEA) was not able to induce contractures in frog
      ventricle suggesting that the contracture evoked by 4-AP is not due to its
      potassium channel blocking effect. In quiescent frog skeletal muscle
      preparations, caffeine as well as 4-AP induced contractures in calcium-free
      solutions. We therefore conclude that there is a caffeine-insensitive, 4-AP
      sensitive intracellular calcium store in the frog ventricle.

PMID- 19585754
TI  - Evaluation of dynamic function tests in normal obese individuals.
AB  - The study was undertaken to assess the dynamic pulmonary function tests in obese
      and non obese young adults of Gharwal (Uttrakhand, India) of 20-40 years age
      group, randomly selected form the employees of Himalayan institute of medical
      sciences, attendants of the patients at the hospital and also from the nearby
      community at Jolly grant, Dehradun. The volunteers representing mixed
      socioeconomic group were categorized into obese cases and non-obese controls as
      per the standard criteria for Body mass index (BMI). Dynamic pulmonary function
      tests were carried out with all the standard protocols. Statistical analysis
      comprised student's "t" test and linear correlation analysis. The result
      indicated a significantly lower value of (FVC) forced vital capacity (2.89 +/-
      0.29) and (FEV1) Forced expiratory volume in 1st sec (2.59 +/- 0.25) in obese
      females. The FVC and FEV1 in the females correlated negatively to the BMI (r = 
      0.376, P < 0.05 and r = -0.359 and P < 0.05) and were significant. Dynamic
      pulmonary function values in males showed a negative correlation but were not
      statistically significant. This concludes that obesity per se has less effect on
      the dynamic function tests in obese young adults except in females, but obese
      individuals presenting with greater morbidity may be more susceptible to altered
      dynamic pulmonary function test in this age group.

PMID- 19585752
TI  - Does the maternal micronutrient deficiency (copper or zinc or vitamin E) modulate
      the expression of placental 11 beta hydroxysteroid dehydrogenase-2 per se
      predispose offspring to insulin resistance and hypertension in later life?
AB  - The relevance of maternal macronutrient deficiency on developmental origin of
      health and adult disorders has been well studied but not that of micronutrients.
      We hypothesized that chronic maternal dietary mineral (copper or zinc) or vitamin
      E restriction modulates the expression of placental 11 beta hydroxysteroid
      dehydrogenase-2 (11 beta HSD-2) per se predisposing the offspring to insulin
      resistance (IR) and hypertension in later life. Female weaning Swiss albino mice
      received a control or a 50% of Vitamin-E or Zn or Cu restricted diet and mated
      with control males. Pups born to the dams on the restricted diet had
      significantly (P < 0.001) reduced body weight and crown rump length. These
      offsprings were weaned on to the restricted diet till postnatal day 180. Glucose
      intolerance in association with hyperinsulinemeia (IR), hyperlipidemeia and
      increased systolic blood pressure were recorded in all the offsprings of
      micronutrient restricted groups. Placental 11 beta HSD-2 expression was
      attenuated, while activities of glucocorticoid -insensitive enzymes were
      unchanged in all the restricted groups. Thus, the present study reiterates the
      importance of micronutrients during pregnancy because chronic maternal
      micronutrient deficiency may alter placental 11 beta HSD-2 expression and
      predispose the offspring to IR and hypertension in later life.

PMID- 19585755
TI  - Correlation of pulmonary function tests with body fat percentage in young
      individuals.
AB  - The present study was planned to assess the correlation of pulmonary functions
      with body fat percentage in young individuals. A total of 132 (males--68, females
      -64) young students (18 to 21 years) with moderately sedentary lifestyle were
      recruited in this study. Their height, weight, body mass index (BMI) and waist to
      hip ratio (WHR) were measured. Pulmonary function tests (static and dynamic) were
      recorded on a computerized portable Schiller lung function unit SP-1. The
      percentage of body fat was estimated by measuring skin fold thickness at four
      sites (4SFT-biceps, triceps, subscapular and suprailiac) with the help of
      Harpenden's caliper. In males body fat % showed negative correlation with
      expiratory reserve volume (ERV), forced vital capacity (FVC), maximum ventilatory
      volume (MVV), peak expiratory flow rate (PEFR) and forced expiratory volume at
      the end of first second (FEV1). It was observed that in females body fat % had
      negative correlation with ERV, FVC, and MVV. These results indicate that increase
      in percentage of body fat and central pattern of fat distribution may affect the
      pulmonary function tests.

PMID- 19585756
TI  - Prevalence and severity of dysmenorrhea: a problem related to menstruation, among
      first and second year female medical students.
AB  - Dysmenorrhea is the most common of gynecologic complaints. It affects half of all
      female adolescents today and represents the leading cause of periodic
      college/school absenteeism among that population. To evaluate the menstrual
      problem specially dysmenorrhea and its severity in female medical students and
      its effect on their regular activities. This is a cross-sectional descriptive
      study; conducted on 107 female medical students, all participants were given a
      questionnaire to complete; questions were related to menstruation elucidating
      variations in menstrual patterns, history of dysmenorrhea and its severity, pre
      menstrual symptom and absenteeism from college and/or class; to detect the
      severity of dysmenorrhea we used the verbal multi-dimensional scoring system,
      participants were given 20 minutes to complete the questionnaire. The mean age of
      subjects at menarche was 12.5 (+/-1.52) years, with a range of 10-15 years. The
      prevalence of dysmenorrhea was 73.83%; approximately 4.67% of dysmenorrhic
      subjects had severe dysmenorrhea. The average duration between two periods and
      the duration of menstrual flow were 28.34 (+/-7.54) days and 4.5 (+/-2.45) days
      respectively. Prevalence of other menstrual disorders like irregularity,
      prolonged menstrual bleeding, heavy menstrual bleeding and PCOD were 7.47%,
      10.28%, 23.36% and 3.73% respectively. Among female medical students who reported
      dysmenorrhea; 31.67% and 8.68% were frequently missing college & classes
      respectively. Premenstrual symptom was the second most (60.50%) prevalent
      disorder and 67.08% reported social withdrawal. Dysmenorrhea and PMS is highly
      prevalent among female medical students, it is related to college/class
      absenteeism, limitations on social, academic, sports and daily activities.
      Maximum participants do not seek medical advice and self treat themselves with
      prostaglandin inhibitors; like Ibuprofen.

PMID- 19585757
TI  - A method for computerised recording and analysis of high frequency biopotentials
      (oscillometry).
AB  - Oscillometry records the high frequency electrical activity on the skin surface.
      These are induced by external ambient electromagnetic radiations, and generated
      internally by physiological processes. The existence of these surface A.C.
      oscillations is fundamental to the existence of an electromagnetic field around
      the human body. Unfiltered electrical and inductive signals are digitally
      recorded using the computer sound card and audio analysis software. The power and
      frequency content of the signal is measured. A sound card with a sample rate of
      96 KHz enables FFT from 0 to 45 KHz. It can be used to study the electrical
      response of the body to externally administered electromagnetic radiations. Some
      of the responses seen during yoga practices are capable of inductive influences.

PMID- 19585758
TI  - Oxidized LDL and paraoxanase status in ischemic stroke patients.
AB  - Stroke is the leading cause of mortality and long term disability among adults in
      industrialized countries. Oxidative stress is an independent risk actor by
      inducing production of oxygen free radicals in ischemic stroke. Because a
      relationship may be associated between ox-ldl and paraoxanase, the aim of this
      study was to investigate the association between ox-ldl and paraoxanase in
      ischemic stroke patients by determining whether ox-ldl is a useful marker for
      monitoring oxidative stress in ischemic stroke patients. Our study included 100
      patients of ischemic stroke and 100 controls. Compared with controls ox-ldl was
      significantly raised in stroke patients and Paraoxanase activity was low. Our
      findings suggest that there is a significant association between raised plasma ox
      ldl and decrease activity of Paraoxanase with age indicating that plasma ox-ldl
      may reflect oxidative stress in ischemic stroke patients.

PMID- 19585759
TI  - Comparative study of NBT reduction method for estimation of glycated protein
      (serum fructoseamine) with glycated HbA1c estimated on DCA 2000+Analyzer
      (immunoagglutination inhibition).
AB  - Glycated protein estimation is a diagnostic tool, used for the long term and
      short term monitoring of the glycemic status of diabetic patients. The present
      study is designed to compare and correlate modified NBT reduction method for the
      estimation of Glycated protein (serum fructosamine) with HbAlc estimated on
      DCA+2000 Analyzer. Glycated protein (serum fructosamine) reduces Nitro Blue
      Tetrazolium (NBT) reagent in alkaline medium to tetrazinolyl radical NBT+ which
      forms a highly colored monoformazen compound, absorbance of which is directly
      proportional to the concentration of glycated protein (serum fructosamine)
      present in the sample and is recorded as delta A/min. The results of modified NBT
      were then compared with HbA1c estimated by immunoagglutination inhibition method.
      Correlation coefficient between HbAlc with serum fructosamine was found to be r =
      0.739 using Schimadzu CL-750 spectrophotometer and r = 0.731 using colorimeter.
      Results of this study were found to be statistically significant P < 0.001. Hence
      this method could be used for routine monitoring of blood glucose control in
      diabetics as HbA1c estimation.

PMID- 19585760
TI  - Effect of paternal smoking on the pulmonary functions of adolescent males.
AB  - OBJECTIVE: The present study was conducted to evaluate the effect of paternal
      smoking on the respiratory function of adolescents. STUDY METHOD: The study group
      comprised thirty healthy males between the ages of 12-18 years whose fathers were
      smokers (Group 1). They were compared with age and sex matched thirty active
      smoker males (Group 2). The control group comprised age and sex matched thirty
      males who were neither active nor passive smokers (Group 3). Pulmonary function
      was assessed using Sibelmed Datospirl20B spirometer in a closed room. RESULTS:
      FEV1/FVC ratio and FEF25%-75% (forced expiratory flow at 25%-75% of vital
      capacity) were significantly lower in the subjects exposed to paternal smoking as
      compared to non-smokers. Vital capacity & expiratory reserve volume were
      significantly lower in active smokers as compared to non-smokers. CONCLUSIONS:
      Our findings suggest a significant reduction in indices of lung functions of
      adolescents exposed to paternal smoke.

PMID- 19585761
TI  - Effect of Raja yoga meditation on the lipid profile of post-menopausal women.
AB  - BACKGROUND: Coronary artery disease is an important cause of death and disability
      among older women. Modification in lipid profile lowers the risk of coronary
      artery disease. It is claimed that yoga and transcendental meditation have a
      cholesterol lowering effect. This study was designed to assess the effect of raja
      yoga meditation of Brahmakumaris which is very simple to practice, on serum
      lipids in normal Indian women. METHODS AND RESULTS: 49 normal female volunteers
      were the subjects. They were divided into pre-menopausal (n=23) and post
      menopausal (n=26) groups. They were further divided into non-meditators (who had
      never done any kind of meditation), short-term meditators (meditating for 6
      months to 5 years) and long-term meditators (meditating for more than 5 years).
      Lipid profile was assessed using their respective reagent sets. Serum
      cholesterol, triglyceride and low-density lipoprotein-cholesterol in
      nonmeditators were significantly more in post-menopausal women as compared to pre
      menopausal women. Serum cholesterol and low density lipoprotein-cholesterol were
      significantly lowered in both short and long term meditators as compared to non
      meditators in post-menopausal women. No significant difference was observed in
      lipid profile in pre-menopausal women. CONCLUSION: Raja yoga meditation lowered
      serum cholesterol and low-density lipoprotein-cholesterol in post-menopausal
      women thus reducing the risk of coronary artery disease in them.

PMID- 19585762
TI  - "Surges".

PMID- 19585763
TI  - Should we teach every soldier how to start an IV?

PMID- 19585764
TI  - Chiropractic in U.S. military and veterans' health care.

PMID- 19585766
TI  - The U.S. Army Wounded Warrior Program (AW2): a case study in designing a
      nonmedical case management program for severely wounded, injured, and ill service
      members and their families.
AB  - This case study describes the innovative and unique U.S. Army Wounded Warrior
      Program (AW2), which provides nonmedical case management to the most severely
      wounded, injured, and ill soldiers and their families. The study describes the
      program and identifies the features for a successful nonmedical case management
      program of an identified population who has complex medical needs. Although the
      article focuses primarily on the role of the AW2 advocate, key components of the
      program are discussed, including successful initiatives as well as areas that
      required adjustment. The lessons learned are identified as well as
      recommendations for future nonmedical case management initiatives.

PMID- 19585765
TI  - The pandemic influenza policy model: a planning tool for military public health
      officials.
AB  - The Pandemic Influenza Policy Model (PIPM) is a collaborative computer modeling
      effort between the U.S. Department of Defense (DoD) and the Johns Hopkins
      University Applied Physics Laboratory. Many helpful computer simulations exist
      for examining the propagation of pandemic influenza in civilian populations. We
      believe the mission-oriented nature and structured social composition of military
      installations may result in pandemic influenza intervention strategies that
      differ from those recommended for civilian populations. Intervention strategies
      may differ between military bases because of differences in mission, location, or
      composition of the population at risk. The PIPM is a web-accessible, user
      configurable, installation-specific disease model allowing military planners to
      evaluate various intervention strategies. Innovations in the PIPM include
      expanding on the mathematics of prior stochastic models, using military-specific
      social network epidemiology, utilization of DoD personnel databases to more
      accurately characterize the population at risk, and the incorporation of possible
      interventions, e.g., pneumococcal vaccine, not examined in previous models.

PMID- 19585767
TI  - Mental health symptoms in combat medic training: a longitudinal examination.
AB  - Mental health symptoms in military populations are rising and constitute a
      significant health concern. This study examined the prevalence of depression,
      anxiety, and suicidal ideation in soldiers (N = 3,792) undergoing combat medic
      training. At the start of training, 10.4%, 15.5%, and 4.1% of soldiers had
      clinically significant depression, anxiety, or suicidal ideation, respectfully.
      These percentages increased to 12.2%, 20.3%, and 5.7% at completion of training,
      respectfully. Worsening of depression, anxiety, and suicidal ideation occurred
      for 7.7%, 11.4%, and 4% of soldiers. Higher percentages of symptoms were
      associated with females, lower education, and lower income. Active duty personnel
      were more likely to worsen following training with respect to suicidal ideation
      (OR = 1.9, 95% CI = 1.2-2.9) compared to reservists. The identification of these
      significant predictors of mental health status may serve to identify individuals
      at risk. Additional work to examine the relative contribution of anticipatory
      (impending deployment) factors vs. training-related factors is warranted.

PMID- 19585769
TI  - Cardiopulmonary resuscitation in the combat hospital and forward operating base:
      use of automated external defibrillators.
AB  - OBJECTIVE: Time to defibrillation (t(defib)) directly correlates with survival
      from cardiac arrest. We investigated whether automated external defibrillators
      (AED) in a combat setting would improve this crucial variable. METHODS: We
      performed a randomized simulation study to compare two systems of cardiac arrest
      response: public access AED vs. standard manual defibrillation. The study was
      conducted in two phases at two different settings: (1) in a contiguous United
      States (CONUS)-based training combat support hospital (CSH) and (2) at a deployed
      CSH within a combat forward operating base (FOB). The primary outcome was
      t(defib) and the secondary outcome was difficulty of use. RESULTS: For the
      training CSH setting, t(defib) the AED model was significantly faster than the
      conventional model (1.3 vs. 2.0 minutes, p <0.001, 95% CI of the mean difference
      = 0.39-1.1). In the combat environment, t(defib) was between 2.2 and 8.4 minutes
      faster for the AED system. The AED system was found to be significantly easier to
      use than the standard model. CONCLUSION: In simulated cardiac arrest, the AED
      model demonstrated significantly improved t(defib) compared to the standard
      response for both training and combat settings.

PMID- 19585768
TI  - A cross-sectional analysis of clinical outcomes following chiropractic care in
      veterans with and without post-traumatic stress disorder.
AB  - This study was a cross-sectional analysis of clinical outcomes for 130 veteran
      patients with neck or low back complaints completing a course of care within the
      chiropractic clinic at the VA of Western New York in 2006. Multivariate analysis
      of variance (MANOVA) was utilized, comparing baseline and discharge scores for
      both the neck and low back regions and for those patients with and without post
      traumatic stress disorder (PTSD). Patients with PTSD (n = 21) experienced
      significantly lower levels of score improvement than those without PTSD (n = 119)
      on self-reported outcome measures of neck and low back disability. These
      findings, coupled with the theorized relationships between PTSD and chronic pain,
      suggest that the success of conservative forms of management for veteran patients
      with musculoskeletal disorders may be limited by the presence of PTSD. Further
      research is warranted to examine the potential contributions of PTSD on
      chiropractic clinical outcomes with this unique patient population.

PMID- 19585770
TI  - A review of the long-term health outcomes associated with war-related amputation.
AB  - The rate of war-related amputations in current U.S. military personnel is now
      twice that experienced by military personnel in previous wars. We reviewed the
      literature for health outcomes following war-related amputations and 17 studies
      were retrieved with evidence that (a) amputees are at a significant risk for
      developing cardiovascular disease; (b) insulin may play an important role in
      regulating blood pressure in maturity-onset obesity; (c) lower-extremity amputees
      are at risk for joint pain and osteoarthritis; (d) transfemoral amputees report a
      higher incidence of low back pain than transtibial amputees; and (e) 50 to 80%
      report phantom limb pain, with many amputees stating they were either told that
      their pain was imagined or their mental state was questioned. The consistency of
      the observations on health outcomes in these studies warrants careful examination
      for their implication in the contemporary treatment of war-related amputation.

PMID- 19585771
TI  - Long-term outcomes of unilateral transtibial amputations.
AB  - BACKGROUND: the long-term outcomes of wartime transtibial amputations have not
      been well documented. The purpose of this case series is to present the long-term
      functional, social, and psychological outcomes of modern-day military unilateral
      transtibial amputees. PATIENTS AND METHODS: the Iranian Veterans Administration
      of the Khorasan province invited their Iranian military amputees from the Iran
      Iraq War (1980-1988) to its medical center for evaluation. The patients filled
      out a detailed questionnaire and were interviewed and examined by each team
      member. RESULTS: two hundred (77%) of the 260 invited amputees were willing and
      able to come back for follow-up. Ninety-six of these patients (48%) were
      unilateral transtibial amputation. The average follow-up was 17.4 years (range 15
      22 years). Land mines were the leading cause of war injury necessitating a
      transtibial amputation (68%). The most common symptoms about their amputated
      limbs were phantom sensations (54%), phantom pain (17%), and stump pain (42%).
      Lower back pain, contralateral (nonamputated limb) knee pain, and ipsilateral
      (amputated limb) knee pain were reported by 44%, 38%, and 13% of subjects,
      respectively. Sixty-five percent of patients were employed or had been employed
      for multiple years after their war injury. All patients were married, and 97% had
      children. Fifty-four percent of amputees reported psychological problems; 26%
      were currently utilizing psychological support services. CONCLUSIONS: at long
      term follow-up, most military transtibial amputees experienced phantom sensation
      or some type of stump pain. More than half had persistent psychiatric problems,
      but only about half of these patients were receiving psychological treatment.
      Although this case series reports the status of these amputees, the next step
      would be to prospectively follow modern wartime amputees using standardized,
      validated outcome measures. With the goal of optimizing long-term amputee
      outcomes, researchers should correlate outcomes with demographics, injury
      characteristics, and treatments to identify and modify factors affecting the
      amputees' prognosis.

PMID- 19585772
TI  - Recovery of multidrug-resistant bacteria from combat personnel evacuated from
      Iraq and Afghanistan at a single military treatment facility.
AB  - U.S. combat casualties from Iraq and Afghanistan continue to develop infections
      with multidrug-resistant (MDR) bacteria. This study assesses the infection
      control database and clinical microbiology antibiograms at a single site from
      2005 to 2007, a period when all Operation Iraqi Freedom (OIF)/Operation Enduring
      Freedom (OEF) casualties admitted to the facility underwent initial isolation and
      screening for MDR pathogens. During this 3-year period, there were 2,242 OIF/OEF
      admissions: 560 in 2005, 724 in 2006, and 958 in 2007. The most commonly
      recovered pathogens from OIF/OEF admission screening cultures were methicillin
      resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter.
      The yearly nosocomial infection rate of these three pathogens among OIF/OEF
      admissions ranged between 2 and 4%. There were remarkable changes in resistance
      profiles for Acinetobacter, K. pneumoniae, and S. aureus over time. Despite
      aggressive infection control procedures, there is continued nosocomial
      transmission within the facility and increasing antimicrobial resistance in some
      pathogens. Novel techniques are needed to control the impact of MDR bacteria in
      medical facilities.

PMID- 19585773
TI  - Suspected acute coronary syndrome in a theater of operations: first management,
      medical evacuation, and final diagnosis: experience of the French Medical Army.
AB  - OBJECTIVE: to evaluate the treatment of the acute coronary syndrome (ACS) among
      soldiers stationed on a theater of operations by structures usually conceived to
      treat combat-related trauma. METHODS: We performed a retrospective study
      involving the whole medical evacuations out of a theater of operations to the
      benefit of the French Armed forces, for a suspected diagnosis of ACS. RESULTS: 35
      patients were included in this study with 20 for a diagnosis of persistent ST
      Segment Elevation Myocardial Infarction (STEMI). Only an active smoking defined a
      population at risk in these high medical selective soldiers. The agreement
      between the initial and the final diagnosis was excellent for STEMI but remains
      perfectible for NSTEMI. CONCLUSION: the medical structures deployed in a theater
      of operations were able to provide first treatment in ACS. The use of powerful
      diagnosis test, like troponine assay, must allow a better selection of the
      patients justifying a medical evacuation.

PMID- 19585774
TI  - A Monte Carlo simulation of air ambulance requirements during major combat
      operations.
AB  - In this study, we evaluate rules of allocation and planning factors that have an
      effect on requirements for Army air ambulance companies. The Army uses rules of
      allocation in scenarios drawn from strategic planning documents to determine how
      many units of each type are required. Army planners use these rules for
      determining the number of units required to support specific operational and
      tactical scenarios. Unrealistic rules result in unrealistic unit requirements. We
      evaluate quantitatively (via Monte Carlo simulation) planning considerations for
      air ambulance units during major combat operations (MCO) and estimate that 0.4
      airframes per admission would be a reasonable planning factor.

PMID- 19585776
TI  - Creatine kinase BB isoenzyme blood levels in trauma patients with suspected mild
      traumatic brain injury.
AB  - This pilot study sought to determine if creatine kinase isoenzyme BB (CK-BB)
      levels might serve as a biological marker of injury severity in mild TBI (mTBI).
      This was a retrospective study of 64 soldiers with suspected mTBI seen in a
      combat support hospital in Mosul between March and August of 2007. Four of the 64
      total samples were positive for CK-BB. One major trauma patient had a negative CK
      BB. This yields a sensitivity of 11% and a specificity of 97%. Military Acute
      Concussion Evaluation (MACE) scores collected also did not appear to reflect
      extent of injury. Although the low sensitivity of CK-BB from this study does not
      support its use as an early marker of suspected mTBI, the result is not
      conclusive given the small sample and the possibility of isoenzyme degradation
      during transport. Although limited, the data collected on MACE scores warrant
      additional evaluation of whether this measure is clinically relevant.

PMID- 19585777
TI  - Survey of severe spatial disorientation episodes in Japan Air Self-Defense Force
      fighter pilots showing increased severity in night flight.
AB  - Spatial disorientation (SD) is one of the most severe causative factors in
      aviation accidents. We analyzed the reported SD episodes to evaluate the
      characteristics of severe SD in fighter pilots. Three hundred seventeen cases
      (95.5%) of 332 total valid cases experienced SD, and the ratio of night and day
      SD experiences (52.7% vs. 47.3%) (p < 0.05) shows a clear prevalence of night SD
      events. The severity of SD episodes at night (2.23 +/- 1.09) was higher than at
      day (1.89 +/- 1.04) (p < 0.01). In addition, the severity of visual illusions was
      significantly higher at night. A significant difference was found for
      meteorological conditions, such as visual meteorological conditions (VMC),
      instrument meteorological conditions (IMC) and VMC-IMC (VI) transition, among
      times of days. In conclusion, the severity of the SD episodes was higher at
      night. This may be due to an increase in visual severe SD episodes at night.

PMID- 19585778
TI  - Exploring deployment experiences of Army medical department personnel.
AB  - The purpose of this study was to describe Operation Iraqi/Enduring Freedom and
      Operation Desert Storm/Shield deployment experiences from the perspectives of 39
      Army Medical Department personnel using a qualitative method in 2004. Thematic
      content analysis revealed themes from data collected during twelve focus groups.
      The themes with the most discussion that transcended across wars, branches,
      echelons of care, and grade were leadership and readiness concerns, followed
      closely by safety issues. The majority of discussion was about deficiency needs
      during deployment and the data suggests that problems experienced during
      deployment are timeless and are not unit-specific; issues were strikingly similar
      across the two wars, as well as across the varying AMEDD roles and types of
      medical units. Therefore, the findings of this study may be generically
      applicable to deployed AMEDD personnel with the potential to alter current policy
      regarding leadership, readiness, and safety for future AMEDD deployments.

PMID- 19585775
TI  - Noninvasive in vivo monitoring of cyanide toxicity and treatment using diffuse
      optical spectroscopy in a rabbit model.
AB  - Currently, no reliable noninvasive methods exist for monitoring the severity of
      in vivo cyanide (CN) toxicity, treatment, and resulting physiological changes. We
      developed a broadband diffuse optical spectroscopy (DOS) system to measure bulk
      tissue absorption and scattering. DOS was used to optically monitor CN toxicity
      and treatment with sodium nitrite (NaNO2). To perform experiments, the DOS probe
      was placed on the hind leg of rabbits. A sodium CN solution was infused
      intravenously. DOS and concurrent physiologic measurements were obtained. After
      completion of CN infusion, NaNO2 was infused to induce methemoglobinemia (MetHb).
      During infusion of CN, blood gas measurements showed an increase in venous
      partial pressure of oxygen (pO2), and following reversal, venous pO2 values
      decreased. DOS measurements demonstrated corresponding changes in hemoglobin
      oxygenation states and redox states of cytochrome-c oxidase (CcO) during CN
      infusion and NaNO2 treatment. Therefore, DOS enables detection and monitoring of
      CN toxicity and treatment with NaNO2.

PMID- 19585779
TI  - Incidence, prevalence, and risk of eating disorder behaviors in military academy
      cadets.
AB  - Eating disorders are a particular problem for college students, as well as
      college athletes and military personnel. We examined the incidence, prevalence,
      and risk of eating disorders at the United States Military Academy (USMA) over a
      7-year period (total population 12,731 cadets). The incidence per year for
      females was 0.02% for anorexia, 0.17% for bulimia, and 0.17% for eating disorders
      not otherwise specified (EDNOS) and for males was 0.0% for anorexia, 0.003% for
      bulimia, and 0.02% for eating disorders not otherwise specified. The total
      prevalence of diagnosed eating disorders for females was 5% and for males was
      0.1%. For females over the 7-year period, we found a prevalence of 0.2% for
      anorexia, 1.2% for bulimia, 1.2% for eating disorders not otherwise specified,
      and for males we found a prevalence of 0.0% for anorexia, 0.02% for bulimia, and
      0.03% for eating disorders not otherwise specified. Nineteen percent of females
      and 2% of males scored a 20 or higher on the Eating Attitudes Test (EAT)-26
      survey indicating they were at risk for developing an eating disorder. We
      conclude that the prevalence of eating disorders at USMA is comparable to
      civilian colleges.

PMID- 19585780
TI  - Descriptive analysis of patients undergoing shoulder surgery at a tertiary care
      military medical center.
AB  - Shoulder pain is a common musculoskeletal complaint. Patients with shoulder pain
      who are seeking care in a military tertiary setting in the United States have not
      been previously described. This study describes the clinical features of 55
      patients (47 men, 8 women) undergoing shoulder surgery at a tertiary care
      military medical center. Patients presenting to a military medical center are
      different than other previously described samples in the literature.
      Specifically, the patients in this study had a known mechanism of injury (n = 42;
      76%), multiple structures involved (n = 46; 84%) and a high prevalence of glenoid
      labral involvement (n = 44; 80%). Further research is needed to determine if
      these patient characteristics identified in this study warrant different
      management strategies and resource utilization in both the tertiary care center,
      and in the primary care center where these patients are typically seen before
      referral to a tertiary care center.

PMID- 19585781
TI  - An easily overlooked injury: Lisfranc fracture.
AB  - We report a case of a 16-year-old male who sustained a Lisfranc (tarsal
      metatarsal joint) fracture after a minor fall. His emergency department (ED)
      presentation, clinical course, and operative repair are presented as well as a
      discussion of Lisfranc fractures to include historical significance. Even after
      minor trauma, an emergency department physician must consider the often elusive
      diagnosis of a Lisfranc fracture in any patient with foot pain.

PMID- 19585782
TI  - Pathogenesis of Burkholderia pseudomallei and Burkholderia mallei.
AB  - Burkholderia pseudomallei and mallei are biological agents of military
      significance. There has been significant research in recent years to develop
      medical countermeasures for these organisms. This review summarizes work which
      details aspects of the pathogenesis of B. pseudomallei and mallei and discusses
      key scientific questions and directions for future research.

PMID- 19585783
TI  - The diagnostic challenge of Hansen's disease.
AB  - Hansen's disease (HD), formerly referred to as leprosy, actively infects more
      than 250,000 persons worldwide, with over 2 million currently being treated for
      sequelae. Over 150 cases are annually reported in the U.S. Although transmission
      of Hansen's disease to military personnel is rare, physicians caring for those
      who deploy abroad should be aware of the diagnostic challenges and therapeutic
      aspects of the disease, as well as its implication for continued military
      service. Additionally, with U.S. involvement in humanitarian efforts abroad, many
      military physicians will encounter this condition in indigenous populations.
      Because of its relative rarity in the U.S. and its protean manifestations,
      diagnosis is generally delayed 6-12 months, leading to potentially irreversible
      sequelae. Therefore the clinician should be aware of the presentation of HD as
      well as the key steps to procuring a diagnosis. This paper reports a case of HD
      encountered in an active duty, native-born U.S. Air Force aviator.

PMID- 19585784
TI  - Phytophotodermatitis: bulla formation and hyperpigmentation during spring break.
AB  - Phytophotodermatitis is a phototoxic dermatologic reaction that occurs with
      exposure to ultraviolet light after contact with certain plant chemicals.
      Recognition is vital to proper management and avoidance of unnecessary distress
      for patients. Sun-sensitizing compounds, known as furocoumarins, are found in
      many plants (limes, celery, and natural grasses) and are excited by ultraviolet A
      (UVA) irradiation. UVA irradiation induces covalent linkages of nuclear DNA
      resulting in cutaneous photosensitivity and vesicular skin damage while
      increasing melanin production. Delayed erythema, hyperpigmentation, and vesicle
      or bullae formation are hallmarks. Literature review reveals most cases occur
      during or after vacation in a sunny destination with exposure to citrus fruit or
      in children playing outdoors in the summer when furocoumarins are abundant.
      Hyperpigmented lesions typically appear on the hands or around the mouth. Overall
      incidence is unknown and there appears to be no predilection for race, although
      typically more easily recognized in the fair skinned. Of concern are the many
      cases where misdiagnosis of child abuse has occurred with unnecessary legal
      action taken and emotional distress for innocent families. Phytophotodermatitis
      is relatively common and easily diagnosed with awareness and a careful history.
      Accurate diagnosis avoids unnecessary concern by patients and potential
      misdiagnosis of abuse. Consider phytophotodermatitis when hyperpigmentation in
      bizarre streaks on sun-exposed areas with vesicles in a nondermatomal
      distribution is present. Presented is an illustrative case.

PMID- 19585785
TI  - Traumatic bladder rupture in a paratrooper.
AB  - A paratrooper presents after a parachuting accident with the inability to
      urinate. Initial emergency bedside ultrasound, followed by confirmatory abdominal
      CT, is carried out and demonstrates an intraperitoneal bladder rupture. The
      patient is taken to the operating room and a 3-layer closure with omental
      buttressing is carried out.

PMID- 19585786
TI  - Prepatellar septic bursitis: a case report of skin necrosis associated with open
      bursectomy.
AB  - Patients with prepatellar septic bursitis are typically successfully managed
      nonoperatively with rest, compression, immobilization, aspiration, and
      antibiotics. Rarely, surgical excision of the bursa may be required for
      recalcitrant cases. Prepatellar bursectomy, however, has been associated with
      considerable risk of surgical-site morbidity. Although skin necrosis is
      frequently cited as a complication of open bursectomy, there is limited
      information in the medical literature on the etiology and management of this rare
      but serious complication.

PMID- 19585787
TI  - Radiology corner. Answer to last month's radiology case and image: gun shot wound
      to the chest of a military working dog.
AB  - This Military Working Dog (MWD) was shot in the chest during combat operations in
      Iraq. Military Working Dogs are critical to the safety and well-being of deployed
      troops in combat operations and, as such, they are triaged and treated in our
      combat hospitals just like any other soldier; their speciation is not a factor in
      their triage status. This case familiarizes military physicians with the basic
      canine anatomy, positioning, and radiological technique they should be aware of
      before deploying. We also strive to raise awareness of the vital roles that these
      MWDs play for our forces, counterany concerns that may arise over the issue of
      treating these dogs in human facilities, and leave the reader feeling better
      prepared to handle the situation should they ever find themselves poised to save
      one of our four-legged warriors.

PMID- 19585788
TI  - Excellence in action. Fort Hood dental activity promotes the importance of oral
      health in schools.

PMID- 19585789
TI  - New delivery method offers improved outlook on impression-taking.

PMID- 19585790
TI  - Helping the special needs patient maintain oral health.

PMID- 19585792
TI  - The role of the OralCdx brush test in preventing oral cancer.

PMID- 19585791
TI  - DECS: experts in the technical side of dentistry.

PMID- 19585793
TI  - Make yourself comfortable.

PMID- 19585795
TI  - Why psychiatric nursing is still the best thing going.

PMID- 19585794
TI  - Advances in caries management.

PMID- 19585796
TI  - Drugs to treat bipolar disorders.

PMID- 19585797
TI  - Restraint debate.

PMID- 19585798
TI  - Restraint debate.

PMID- 19585799
TI  - The antidepressant effects of anticholinergic drugs.
AB  - Acetylcholine is a neurotransmitter that is important for communication between
      neurons and muscle, is involved in direct neurotransmission in the autonomic
      parasympathetic nervous system, and has been implicated in cognitive processing,
      arousal, and attention in the brain. The cholinergic-adrenergic hypothesis of
      mood disorders states that a given affective state might represent a balance
      between central cholinergic and adrenergic neurotransmitter activity in those
      areas of the brain regulating moods. According to this hypothesis, depression
      would be the clinical manifestation of a state of cholinergic dominance, whereas
      mania would reflect adrenergic dominance. On the basis of this hypothesis,
      anticholinergic drugs have been investigated as potential treatments for
      depression, but study results have not shown consistent antidepressant effects.
      However, the dosage dependency of scopolamine's effect across different studies
      and the lack of antidepressant effects with other anticholinergic drugs suggest
      that a specific muscarinic receptor subtype might be most relevant to the
      potential antidepressant mechanism of action of anticholinergic drugs.

PMID- 19585800
TI  - Youth in the mental health void: wraparound is one solution.
AB  - Mental health treatment works-if you can gain access to it. For many U.S.
      children with mental disorders, treatment is so inaccessible that parents must
      terminate their custodial rights so their children can receive psychiatric care.
      Use of Safe Haven laws, originally intended to prevent abandonment of newborns,
      are now being used to provide basic mental health care to youth. The closing of
      psychiatric services during the past decade has contributed to this crisis. Yet,
      one solution, wraparound systems of care, holds tremendous promise for providing
      community-based, comprehensive, and cost-effective care. Psychiatric nurses
      should support wraparound services as the standard of care for children and their
      families as health care reform is initiated.

PMID- 19585801
TI  - Caregivers of victimized children: differences between biological parents and
      foster caregivers.
AB  - Caregivers of children who have been sexually abused often find the experience
      challenging, especially when the child begins to act out in the home. Many
      children who have engaged in sexually aggressive, sexually inappropriate, or
      coercive behaviors with other children are placed in foster care. The purpose of
      this article is to describe the characteristics of biological parents and their
      significant others and foster caregivers of sexually aggressive and abusive
      children. A descriptive, exploratory study was conducted involving 3,149
      caregivers (1,764 of them foster caregivers) of more than 800 youth ages 3 to 20.
      Findings suggest that while the foster caregivers were a more stable group than
      the biological parents and their significant others, the children experienced
      significantly high levels of instability in foster care placement. Provision of
      emotional and psychosocial support, coupled with education and periodic health
      evaluations, for the foster caregivers may be focal points of interventions.
      Nurses are in an ideal position to provide positive health promotion strategies
      and lifestyle choices for both foster caregivers and the children.

PMID- 19585802
TI  - Clinical practice guideline: 1-hour face-to-face assessment of a patient in a
      mechanical restraint.
AB  - Face-to-face assessment within 1 hour after placing a patient in a restraint has
      been the standard of care following regulatory requirements set forth by the
      federal government in 1999. This rule, although widely followed and applauded as
      optimum patient care, has little evidence of a standardized format for what
      constitutes the examination. Health care providers agree that a face-to-face
      assessment is warranted; however, no set parameters exist for what constitutes
      the key elements of such an assessment. This clinical practice guideline offers a
      specific outline to follow that emphasizes the safety of the patient being placed
      in a mechanical restraint for a behavioral health emergency.

PMID- 19585803
TI  - Suicide risk assessment: 6 steps to a better instrument.
AB  - Recent research indicates that commonly used instruments to assess suicidal
      ideation identify patients at chronic risk for suicide but do not identify those
      who are at acute (imminent) risk for suicide while hospitalized. Items to measure
      anxiety and agitation, identified as more appropriate risk factors, should be
      incorporated into suicide risk assessments. The purpose of this article was to
      develop an evidence-based imminent suicide risk instrument for an inpatient
      psychiatric unit. The Iowa Model of Evidence-Based Practice to Promote Quality
      Care guided development. Two validated instruments, the Hamilton Anxiety Scale
      (to measure anxiety) and the Behavioral Activity Rating Scale (to measure
      agitation) were applied to 75 patients to help create an evidence-based
      instrument, which should more accurately identify hospitalized patients at risk
      for imminent suicide.

PMID- 19585804
TI  - 'State of the art' conference looks for ways to improve on the past.

PMID- 19585805
TI  - Declarative titles for journal articles: for better or for worse?

PMID- 19585806
TI  - Making PQRI work in a nephrology practice.

PMID- 19585807
TI  - Why Obama's health reform plan might actually work.

PMID- 19585808
TI  - How to make the new conditions for coverage work in your dialysis clinic:
      Teaching self-management: new conditions emphasize patient participation in care.

PMID- 19585809
TI  - Disaster response and dialysis: Hurricane Ike provides serious test of emergency
      response plan.

PMID- 19585810
TI  - Projected impact of the proposed "bundled" ESRD payment system on a small
      dialysis organization.
AB  - Payment for outpatient hemodialysis services is currently made by the Centers for
      Medicare & Medicaid Services on a per-treatment basis using a partially "bundled"
      composite rate adjusted for geographic and patient characteristics, plus a
      separately billable portion for medications and services not included in the
      bundle. In response to concerns over rising costs of the End-Stage Renal Disease
      Program, and specifically the increasing use of erythropoiesis-stimulating
      agents, Congress has mandated a new, more inclusive prospective payment system,
      in which current composite rate services, separately billable medications, and
      dialysis-related laboratory services will be included in a single payment. It is
      expected that the so-called bundle will apply a geographic wage adjuster and
      patient-specific case-mix factors to a base rate to calculate a per-patient, per
      treatment payment unit. We have modeled the proposed bundle and entered clinical
      and financial data for 118 Medicare patients dialyzed at a suburban dialysis
      center in New York State during 2006. Under the proposed bundled system, we stand
      to lose as much as $118,000 per year in revenue, and we find the case-mix
      adjusters appear to be poor predictors of our actual costs. We conclude that the
      proposed bundle places the small dialysis provider at significant financial risk.

PMID- 19585811
TI  - Let the government bail you out: how physicians can recover investment losses
      with tax benefits.

PMID- 19585812
TI  - Medical education in today's perspective.

PMID- 19585813
TI  - High prevalence of undetected thyroid disorders in an iodine sufficient adult
      south Indian population.
AB  - India is in the transition phase from iodine deficiency to iodine sufficiency,
      and this is expected to change the thyroid status of the population. The thyroid
      status and auto-immune status of adult Indian population in the postiodisation
      phase is largelyunknown, and this study was conducted to answer this question. A
      cross-sectional population survey was conducted in two phases among the residents
      of urban coastal area of central Kerala. The initial phase included a house-to
      house survey of 3069 adults (>18 years of age), selected by cluster sampling
      method. From the surveyed population, 986 subjects underwent further physical
      examination and biochemical evaluation for thyroid function, thyroid autoimmunity
      status and iodine status. The total prevalence of goitre was 12.2% and median
      urine iodine excretion was 211.4 mcg/l (mean 220.3 +/- 99.5 mcg/l) indicating
      iodine sufficiency. Thyroid function abnormalities were present in 19.6% of
      subjects. Subclinical hypothyroidism was present in 9.4%. Among the population
      with normal thyroid function, 9.5% and 8.5% respectively had positive anti-TPO
      and anti-TG antibodies. Among those with thyroid dysfunction, 46.3% had positive
      anti-TPO and 26.8% were anti-TG positive. A significant proportion of this iodine
      sufficient adult population had thyroid disorders. Further studies are required
      to characterise the reasons for this high prevalence. Iodine deficiency as well
      as thyroid dysfunction should both be the focus of public health strategies in
      susceptible populations.

PMID- 19585814
TI  - Influence of oxidants and anti-oxidants on semen parameters in infertile males.
AB  - The deleterious effect of free radicals on spermatozoa was assessed by estimating
      malondialdehyde and vitamins E and C in seminal plasma and their relation with
      different sperm parameters. Twenty-two fertile controls with 74 primary infertile
      males were analysed in the department of biochemistry, SCB Medical College,
      Cuttack. Seminal malondialdehyde level was observed to be raised in all infertile
      groups except azoospermic cases in comparison to control. Levels of vitamins E
      and C were significantly low in the infertile cases (p < 0.001) in relation to
      control. Significant positive correlation between malondialdehyde with total
      sperm count and leucocyte count (p < 0.01) indicates their dual contribution
      towards free radical generation. The negative association of semen
      malondialdehyde with normal sperm motility and morphology suggests damaging
      effect of free radicals on sperm membrane integrity. Marked negative correlation
      of seminal malondialdehyde with both the vitamins signifies their protective
      utilisation during oxidative phenomenon. In conclusion, understanding the
      physiologic and pathologic effects of free radicals on sperm function will help
      in designing new and effective treatment strategies in male infertility.

PMID- 19585815
TI  - Association of risk factors with spontaneous preterm birth after 28 weeks and
      neonatal outcome--a case-control study in a tertiary care referral centre.
AB  - This prospective case-control study was carried out in patients admitted in
      Government Lady Goschen Hospital, Mangalore to study the risk factors associated
      with spontaneous preterm birth after 28 weeks and its neonatal outcome when
      compared with term birth. One hundred women who were admitted in labour of
      gestational age 28 to 37 weeks were included in study group and similarly 100
      women of more than 37 weeks were in the control group. Height, weight and body
      mass index were significant risk factors associated with preterm birth. When
      maternal weight increases, the chance of term delivery increased 10%. Previous
      preterm births and spontaneous abortions increasedthe risk of preterm birth.
      Birth weight and Apgar score were significantly lower in study group. Neonatal
      morbidity and mortality were significantly higher in study group. Qualitative
      variables in frequencies were analysed using Chi-square test. Quantitative
      variables in mean were analysed using Student's independent 't' test.
      Multivariate analysis using logistic regression was done to identify the
      significant factor. It can be concluded that maternal anthropometry and previous
      obstetric performance are the important factors. These women at risk should be
      identified and adequate antenatal care to these women might decrease the
      incidence of preterm birth. Prolongation of gestation and increase in birth
      weight give favourable neonatal outcome. Good neonatal intensive care unit will
      not only improve the outcome of preterm birth but also will decrease the
      socioeconomic burden to the parents, society and the nation.

PMID- 19585816
TI  - Deliberate self-harm prevention in the Sundarbans region need immediate public
      health attention.
AB  - Deliberate self-harm is a major public health problem. This study is aimed to
      examine the sociodemographic characteristics of both non-fatal and fatal
      deliberate self-harm cases admitted at the 13 block primary health centres of the
      Sundarbans region under South 24 Parganas district, West Bengal. Retrospective
      deliberate self-harm data from the admission registers of 13 block primary health
      centres was collected for the year 1999. A total of 1850 deliberate self-harm
      cases (639 males and 1211 females) were admitted at the 13 block primary health
      centres, of which 159 (60 males, 99 females) were fatal (completed suicide). A
      higher fatality rate for male than female (9.4% compared to 8.2%) was observed.
      Women (65.5%), especially of younger age groups constituted the major cases.
      Poisoning (96.9%) was the commonest method of self-harm. Easy availability of
      pesticides was a common factor. Marital status and seasonal trend (March-April)
      had important contribution in self-harm incidents. Planned psychosocial
      intervention as a part of community mental health programme may help to reduce
      the deliberate self-harm morbidity and mortality at this primary care level.

PMID- 19585817
TI  - A comparative study of two techniques of urethroplasty in repair of distal penile
      hypospadias.
AB  - Hypospadias is a common congenital anomaly of the penis in which the urethra
      opens proximal to its normal position at the tip of the glans and the overall
      incidence of hypospadias is between 0.3% and 0.6%. Distal penile hypospadias is
      the commonest amongst all hypospadias cases. One stage urethroplasty was
      performed among 64 cases using Mathieu-Mullen's procedure or Snodgrass Belman
      procedure. Of these 64 cases, in 29 cases the Mathieu-Mullen's procedure was
      followed and in the rest 35 cases of distal penile hypospadias the Snodgrass
      Belman procedure was employed. These two procedures were retrospectively compared
      in terms of operating time, operative blood loss, cosmetic result, postoperative
      fistula rate, duration of operation.

PMID- 19585818
TI  - Evaluation of intensive pulse polio immunisation in south Gujarat region of
      India.
AB  - Randomly selected team members of 50% booths in urban areas of Surat, Valsad and
      Bharuch districts and 25% in tribal areas of Narmada and Dangs districts of South
      Gujarat region were Interviewed to evaluate the pulse polio immunisation coverage
      in urban and tribal areas of South Gujarat region. Evaluation of two consecutive
      rounds of pulse polio immunisation had shown that the booth coverage is about 90%
      and 80% in urban and tribal areas respectively. Television was the main source of
      information for pulse polio round in urban areas, while anganwadi workers were in
      tribal areas. During house to house activity, few unimmunised children were
      found. X to P conversion was found almost nil at the end of day in both the
      rounds. The present study shows the deficits in programme implementation even
      after many years of campaigning and provides extents to which strengthening Is
      needed especially in urban area.

PMID- 19585819
TI  - Aetiopathological and clinical study of erythroderma.
AB  - Erythoderma first described by Hebra in 1868 is a reaction pattern, characterised
      by generalised and confluent erythema with desquamation affecting more than 90%
      of body surface and is usually accompanied by systemic manifestation including
      some metabolic changes. Tile study was envisaged to assess their profile of
      aetiology, clinical features and to correlate with histopathological findings.
      Twenty-four patients (18 males and 6 females) with erythroderma were considered
      for the study. All patients were hospitalised, detailed history was taken and
      were subjected to relevant investigations--haemogram, serum proteins, liver and
      renal function tests, routine and microscopic urine tests, HIV screening, x-ray
      chest, ultrasound abdomen, FNAC of enlarged lymph nodes and skin biopsy. The age
      group affected ranged between 7 and 70 years, peak incidence between 50 and 60
      years. The male to female ratio was 3:1. Scaling, erythema and pruritus were
      predominant clinical manifestations. In 12 clinically suspected psoriatic
      erythroderma, only in 6 cases the histopathological features were correlated to
      psoriasis and remaining showed non-specific chronic dermatitis. Two patients were
      found to be HIV-positive. There is good clinicopathological correlation in
      erythroderma caused by lichen planus, atopic dermatitis, seborroeic dermatitis,
      non-bullous congenital ichthyosiform erythroderma. Drugs were found to be
      aetiological factor in 3 cases. The study was conducted to assess variations in
      clinical, aetiological and histopathological profile of erythroderma. The present
      series had high percentage of erythroderma secondary to preexisting dermatoses.
      The onset of disease was insidious except in drug-induced erythroderma where it
      was acute.

PMID- 19585820
TI  - A case of psychogenic purpura in a female child.
AB  - Recurrent spontaneous cutaneous bruising or bleeding through intact skin may be
      due to underlying emotional stress which may be due to auto-erythrocyte
      sensitisation. A 9-year-old female child presented with recurrent episodes of
      oozing from the skin of both lower eyelids and lower peri-orbital areas along
      with bleeding from tongue which ceased spontaneously after a few minutes without
      having any induration or oedema at the sites. The child had no systemic
      abormality, but she was nervous and attention seeking. Psychologic assessment
      revealed that she was suffering from conversion anxiety and somatoform disorder.
      After twelve psychotherapeutic sessions she showed marked improvement and her
      symptoms did not recur.

PMID- 19585821
TI  - Ewing's sarcoma/ primitive neuro-ectoclermal tumour: a case report.
AB  - Ewing's sarcoma/primitive neuro-ectodermal tumour on medial end of the left
      clavicle is a rare site. Here is a case of 16-year-old female presented with
      gradually increasing swelling at medial end of clavicle, showing osteolytic
      lesion on x-ray and CT. Cytology showed features of Ewing's sarcoma, but
      histopathologically diagnosed as poorly differentiated small cell carcinoma.
      Marker study was carried out, and it confirmed Ewing's sarcoma. After 3 to 6
      month of continuous therapy patient presented with axillary lymph node and skull
      vault metastasis, again a rare site for secondaries in Ewing's sarcoma.

PMID- 19585822
TI  - Urethral carcinoma mimicking scrotal cancer.

PMID- 19585823
TI  - Snakebite death.

PMID- 19585824
TI  - A postmarketing surveillance study of dexrabeprazole in the treatment of acid
      peptic disorders.
AB  - Dexrabeprazole [R(+) rabeprazole] is a novel proton-pump inhibitor which has
      recently become available in India for the treatment of acid peptic diseases.
      Experimental and clinical studies have shown superiority of dexrabeprazole (at
      half the recommended rabeprazole dose) over rabeprazole in terms of favourable
      pharmacokinetics, better efficacy and faster and greater healing activity.
      Results of present study in a large population of 4931 patients of acid peptic
      disorders, reconfirmed safety and efficacy of dexrabeprazole 10 mg once daily in
      the treatment of gastro-oesophageal reflux disease and also showed its
      effectiveness in the treatment of patients with peptic ulcers (gastric/duodenal).

PMID- 19585825
TI  - Compiled report on clinical efficacy and safety of nifedipine retard
      10/20/nifedipine CD 30, as a first-line/add-on therapy in patients of
      hypertension: ENHANS trial.
AB  - The effectiveness of long acting nifedipine (Nicardia retard 10/20/30 CD) was
      evaluated on Indian patients in multiple centres. This was an open, prospective,
      clinical multicentric trial. Nearly 1632 patients satisfying the inclusion
      criteria were selected and given long acting nifedipine and assessed regularly
      for a period of one month. The reduction in the arterial blood pressure was
      significant from the 3rd day onwards and the target systolic and diastolic blood
      pressures were reached by the 14th day and the 7th day respectively, without
      notable changes in other parameters. At the final visit 18.6% and 16.1% reduction
      from the baseline was witnessed in the systolic and diastolic blood pressures
      respectively; 67.3% and 76% of individual patients had achieved target systolic
      and diastolic pressures respectively at end of one month. The heart rate was also
      found to be significantly reduced in the course of the trial (2.1% from the
      baseline). No other physical and investigational parameters were affected.
      Moreover 56.3% and 55.8% patients and physicians respectively rated the treatment
      as "very good" or "excellent" at the end of the study period. Thus, from this
      trial it is clear that long acting nifedipine is very efficacious as a first-line
      drug in the armamentarium against hypertension, while controlling other
      modifiable risk factors for cardiovascular disease.

PMID- 19585826
TI  - [Who the hell wants to be in charge in psychiatry].

PMID- 19585827
TI  - [Correctly measured blood pressure, thanks!].

PMID- 19585828
TI  - [Mechanical heart pump an alternative when transplantation is contraindicated.
      Permanent treatment now possible thanks to a rapid development].

PMID- 19585829
TI  - [Drugs and desperation in different worlds. Abuse of cathinone and
      methcathinone].

PMID- 19585830
TI  - [Carotid body tumors--a multidisciplinary matter].

PMID- 19585831
TI  - [Multidisciplinary focus on cognitive failure and dementia].

PMID- 19585832
TI  - [Dementia].

PMID- 19585833
TI  - [Lewy body dementia--big risk of wrong treatment and death].

PMID- 19585834
TI  - [Vascular cognitive impairment a spectrum of diseases].

PMID- 19585835
TI  - [Frontotemporal dementia heterogeneous group of diseases].

PMID- 19585836
TI  - [Biomarkers in cerebrospinal fluid and blood in memory complaints].

PMID- 19585837
TI  - [Brain imaging--a support in the investigation of dementia].

PMID- 19585839
TI  - [The zero vision for suicide--what is the alternative?].

PMID- 19585838
TI  - [Rare mutations aim toward future treatment].

PMID- 19585840
TI  - [Contradictory about the zero vision for suicide].

PMID- 19585841
TI  - [Goals and means for suicide prevention].

PMID- 19585842
TI  - [Follow up studies as a condition for drug subsidizing].

PMID- 19585844
TI  - [The Medical Products Agency supports clinical research].

PMID- 19585845
TI  - [Health care--an industrial system?].

PMID- 19585843
TI  - [TLV exceeds it mandate in its drug survey].

PMID- 19585846
TI  - [The criticized theory of Darwin viable in the long run].

PMID- 19585847
TI  - The NHS dentistry review.

PMID- 19585848
TI  - Medical emergencies in dental practice: 2. Management of specific medical
      emergencies.
AB  - In the second of two papers on the diagnosis and management of medical
      emergencies, the measures needed to manage specific medical emergencies are
      discussed. Each emergency requires a correct diagnosis for effective and safe
      management. Signs and symptoms are highlighted at the beginning of each section
      describing patient management. The basis of management in contemporary dental
      practice avoids the intravenous route of drug administration, where drugs are
      required. CLINICAL RELEVANCE: All dental practitioners require a knowledge of the
      management of specific medical emergencies.

PMID- 19585849
TI  - Current methods of shade matching in dentistry: a review of the supporting
      literature.
AB  - The difficulties of shade matching in dentistry are discussed and various
      suggestions are given to improve the process. Several authors have described
      shade-taking routines with the aim of improving shade-matching. These are
      summarized and a method for choosing the appropriate shade from the previous
      guidelines is given. The scientific principles and evidence-base behind the new
      technique are given. The problems and advantages of instrumental shade-taking
      devices are reviewed. CLINICAL RELEVANCE: Consistent and correct shade selection
      is fundamental to the placement of aesthetic restorations which are an essential
      part of everyday practice.

PMID- 19585850
TI  - Local anaesthesia: risks and controversies.
AB  - This paper describes the complications that can occur as the result of the intra
      oral injection of local anaesthetics. It considers important localized and
      systemic complications and describes strategies to limit the occurrence of such
      problems. CLINICAL RELEVANCE: Local anaesthetics are routinely administered
      during many dental procedures. An understanding of the risks involved in these
      injections is important.

PMID- 19585851
TI  - A novel approach to bridge design.
AB  - This case report describes a novel approach to bridge design using fibre
      reinforced composite materials. CLINICAL RELEVANCE: By thinking 'outside the box'
      clinicians may be able to use modern materials in unusual clinical situations.

PMID- 19585852
TI  - Nicotine-induced osteonecrosis. A case report.
AB  - This paper describes a previously unpublished side-effect of nicotine replacement
      chewing gum and presents useful information about the effects of nicotine on the
      oral environment. It is important to consider this when diagnosing an area of
      ulceration. CLINICAL RELEVANCE: Patients who use nicotine chewing gum should be
      advised that prolonged contact with the alveolar mucosa should be avoided. They
      should be told that regular chewing helps dispersal of the nicotine.

PMID- 19585853
TI  - Surviving child sexual abuse: the relevance to dental practice.
AB  - Child sexual abuse (CSA) occurs in all communities, ethnic backgrounds,
      religions, cultures, social and economic classes, and is experienced by both
      males and females. The physical and psychological effects of CSA have significant
      effects on adult health outcomes. Parallels have been drawn between the physical
      and emotional environment of dental treatment and features of the CSA experience.
      Consequently, adult survivors of CSA can find it difficult to tolerate dental
      treatment, and may repeatedly cancel dental appointments or avoid dental
      treatment altogether. Awareness of patient characteristics in the dental setting
      that indicate past CSA include discomfort with body positioning, dislike of being
      touched, sense of loss of control, fear of judgement and sensitivity to perceived
      criticism, sensitivity to particular smells and sensitivity to having instruments
      in the mouth. Some aspects of the dental environment and dental treatment can act
      as 'triggers' that can take survivors of CSA back to the emotions associated with
      that event. An understanding of the fears and anxieties this can cause in the
      dental setting allows the dental team to help the individual cope with the dental
      experience, improving it for both the patient and the provider. The development
      of general strategies that foster establishing a positive rapport, sharing
      control and treating the individual as a partner in the healthcare relationship
      can cultivate a positive dental experience that can have far reaching effects.
      CLINICAL RELEVANCE: The prevalence of child sexual abuse (CSA) is surprisingly
      high, so adults who have experienced CSA can find it difficult to tolerate dental
      treatment, and may repeatedly cancel dental appointments or avoid dental
      treatment altogether.

PMID- 19585854
TI  - Tooth-supported, magnet-retained overdentures: a review.
AB  - There has been an increase in the provision of implant-supported prostheses in
      patients unable to tolerate conventional dentures. Unfortunately, many patients
      are unable to benefit from this treatment option because of anatomical, medical
      or financial constraints. Magnet-retained overdentures represent a potential
      treatment option in many of these cases. This article describes the development,
      advantages, complications and clinical procedures associated with the provision
      of tooth-supported, magnet-retained overdentures. CLINICAL RELEVANCE:
      Conventional overdenture retention can be enhanced by the use of dental magnets.
      Clinical procedures are straightforward and magnets offer a number of advantages
      over other forms of precision attachment.

PMID- 19585855
TI  - Bilateral TMJ dislocation in a 23-month-old infant: a case report.
AB  - Dislocation of the temporomandibular joint (TMJ) is rare in children. We present
      the second youngest case reported. Diagnosis was delayed owing to failure to
      recognize important clinical signs. We outline how this problem can be recognized
      and treated, and propose radiographic confirmation of the clinical diagnosis
      which is not necessary if there is no history of direct mandibular trauma. Two
      new clinical signs are demonstrated. CLINICAL RELEVANCE: TMJ dislocation is of
      relevance to all dental professionals because it can occur in the dental chair
      and because dental professionals are often called upon to manage this condition.

PMID- 19585857
TI  - Physical signs for the general dental practitioner. Case 65. Rheumatoid
      arthritis.

PMID- 19585856
TI  - Hot topics in special care dentistry. 3. Older people.

PMID- 19585858
TI  - Aspects of human disease: 34. Alcoholism.

PMID- 19585859
TI  - Oral food challenge in children: an expert review.
AB  - Oral food challenges are indicated for the diagnosis of food allergy and the
      double-blind, placebo-controlled oral food challenge is considered the gold
      standard diagnostic method in children with suspected food allergy. This practice
      parameter for oral food challenges in children was prepared by a workgroup at the
      request of the French Society for Allergology and Clinical Immunology (SFAIC) and
      the French Paediatric Society for Allergology and Pulmonology (SP2A). We aimed to
      develop practical guidelines for oral food challenges in children for the
      diagnosis of suspected food allergy or the evaluation of food tolerance. We also
      considered the safety measures to be implemented during testing and management of
      the potentially serious allergic reactions that may arise during the test. The
      strength of the recommendations was established, using the GRADE evidence-based
      approach. We considered four issues: (1) the selection of children for oral food
      challenges (indications and contraindications); (2) the procedure used (material,
      where the test should be carried out, technique and management of reactions); (3)
      interpretation of the test and (4) consequences of the test.

PMID- 19585860
TI  - Multiple drug hypersensivity: insight into the underlying mechanism and
      correlation with autoimmune diseases.
AB  - BACKGROUND: Subjects with drug hypersensitivity are sometimes simultaneously
      reactive to several drugs. This nosological entity is defined as multiple drug
      hypersensivity (MDH). Urticaria and angioedema are the commonest clinical
      manifestations of hypersensitivity drug reactions (HDR). These clinical signs are
      also pathognomonic of chronic idiopathic urticaria (CIU), whose pathogenetic
      mechanisms are still largely unknown. The diagnostic algorithm of CIU includes
      autologous serum skin test (ASST) and autologous plasma skin test (APST), which
      demonstrated a high positive and negative predictive value, in multiple
      nonsteroidal anti-inflammatory drugs (NSAIDs) intolerance. OBJECTIVE: to explore
      the underlying mechanism of MDH and to assess the correlation between such tests
      and autoimmune diseases (AD). METHODS: Twenty eight subjects with MDH referred to
      our Allergy/Immunology Unit were enrolled from May 2006 to May 2007. Eight
      healthy subjects served as controls. In addition to common diagnostic tools used
      in the diagnostic algorithm of MDH, enrolled subjects also underwent ASST and
      APST. RESULTS: Patients were predominantly female (23 female vs. 5 male; mean age
      52.2 years). In 61% of cases MDH was associated with either CIU or AD. NSAIDs and
      antibiotics were the major causes of HIDR, both implied in 54% of subjects. The
      proportions of MDH-subjects with positive ASST and APST were 46.4% and 28.6%,
      respectively. All patients with MDH+AD+CIU (4/4) presented apositive ASST.
      CONCLUSIONS: In patients with MDH, ASST proved to be frequently positive, as
      previously described for multiple NSAIDs intolerance. In ASST-positive subjects,
      the activity of several drugs appears to add up FceRI-specific autoantibodies in
      the induction of the release of allergic mediators.

PMID- 19585861
TI  - Simultaneous occurrence of chronic autoimmune urticaria and non-allergic asthma:
      a common mechanism?
AB  - Chronic urticaria is now considered as an autoimmune disorder due to histamine
      releasing autoantibodies in 40-50% of cases. These histamine releasing
      autoantibodies directed against the high affinity IgE receptor or against IgE can
      be detected in vivo by autologous serum skin test (ASST) or in vitro by a
      functional assay employing basophils. ASST positivity has been found also in
      patients with non-allergic asthma, but its relevance to the disease mechanism
      remains to be defined. Here, we report two women aged 43 and 75 years who
      complained simultaneous occurrence of chronic urticaria and asthma. Circulating
      histamine-releasing factors were detected in both patients by ASST and basophil
      histamine release assay whereas other possible causes of urticaria and asthma
      were excluded by clinical and laboratory investigations. The elder woman had
      associated autoimmune thyroiditis. We suggest that circulating histamine
      releasing factors, probably represented by histamine-releasing autoantibodies,
      might be involved in the pathophysiology of both chronic urticaria and asthma.

PMID- 19585862
TI  - A case of protracted hypotension as unique symptom of a biphasic anaphylaxis to
      amoxicillin.
AB  - We are reporting a case of one patient who have experienced itching of palms and
      soles, thorax erythema, conjunctive injection immediately after oral
      administration of amoxicillin, and hypotension after 3 hours. In E.D. hypotension
      was monitored because he was a cardiopatic but it wasn't treated even if it was
      protracted. A positive result of immediate-reading intradermal test with
      amoxicillin at 2 mg/ml concentration was found confirming the diagnosis of
      allergic biphasic anaphylaxis to amoxicillin.

PMID- 19585863
TI  - Phenobarbital-induced DiHS and ceftriaxone hypersensitivity reaction: a case of
      multiple drug allergy.
AB  - Patients with DiHS show an increased risk of sensitization to multiple drugs. We
      report a case of a young woman who developed cutaneous rash, lymphoadenopathy,
      malaise and fever after the introduction of phenobarbitale. Because of these
      symptoms, she was treated with ceftriaxone and she experienced a severe flare-up
      of the cutaneous and general reaction. Allergological work-up, by cutaneous and
      lymphocyte transformation test, confirmed a double sensitization to phenobarbital
      and ceftriaxone. In conclusion, the high risk of DiHS during anticonvulsive
      therapy should suggest caution in using additional drugs, because of an increased
      risk of multiple reactions.

PMID- 19585864
TI  - [Health on this side of the wall: a bridge between Salento (Italy) and
      Palestine].

PMID- 19585865
TI  - [Latest criticism of the study on health and waste management in the Campania
      Region].

PMID- 19585866
TI  - [A field epidemiologist writes to E&P].

PMID- 19585867
TI  - [Endocrine disrupters: from research to risk assessment].

PMID- 19585868
TI  - [Assessing the effectiveness of actions for reducing air pollution in urban
      areas].

PMID- 19585869
TI  - [Milano, Ecopass--fee for particulate air pollution].

PMID- 19585870
TI  - [The city administration of Milan provides the figures for Ecopass (air pollution
      fee)].

PMID- 19585871
TI  - [Young epidemiologists between insecurity and tenure].

PMID- 19585872
TI  - [The effects of the traffic restriction fee (Ecopass) in the center of Milan on
      urban pollution with particulate matter: the results of a pilot study].
AB  - BACKGROUND: the city of Milan introduced a traffic charging zone in city center
      in January 2008, named Ecopass. AIM OF THE STUDY: to compare PM1, PM2,5 and PM10
      levels in and outside the restricted area before and after the enforcement of the
      charging scheme. METHODS: PM1, PM2,5 and PM10 exposures were measured by means of
      pre-calibrated portable laser-operated particle analyzers. PM10 data from the
      ARPA official monitoring stations were also evaluated. RESULTS: during a walking
      trip from Piazza Loreto (outside) to Piazza Duomo (inside Ecopass zone) and back,
      mean (SD) PM1, PM2,5 and PM10 were 31 (6), 68 (24) and 93 (37) microg/m3 inside
      the Ecopass zone, and 32 (6), 70 (37), 98 (48) microg/m3 in the outer area,
      respectively (not significant, ns). In another trip walking from Piazza
      Buonarroti to Piazza Duomo and back, PM1, PM2,5 and PM10 levels were 56 (2), 183
      (14) and 245 (28) microg/m3 inside the Ecopass zone, and 58 (3), 197 (13) and 247
      (24) microg/m3 in the outer area, respectively (ns). In the measurements taken
      from a car moving in three ring belts--one inside the restricted zone, and two
      outer radial orbitals--PM1, PM2,5 and PM10 levels were found 41 (1), 110 (8) and
      148 (16) microg/m3 inside the Ecopass area, 42 (3), 116 (14) and 152 (28)
      microg/m3 along the middle belt, and 39 (4), 102 (15) and 127 (23) microg/m3
      along the greater Milan orbital ("Tangenziale"), respectively (ns). Mean (SD)
      PM10 levels from ARPA in the two months before the enforcement were 71.2 (32.6)
      and 74.8 (38.4) microg/m3, in the Ecopass zone and outside, respectively while
      after the enforcement were 67.3 (36.4) and 70.9 (38.3) microg/m3 of PM10,
      respectively (ns). CONCLUSIONS: no signficant improvement in air quality was
      observed after the enforcement of the Ecopass charging zone in Milan. In spite of
      their limitations, the present data confirm that small scale reductions in
      particle emissions are not sufficient to reach the goal of an improvement in air
      quality. Large scale, coordinated interventions on an inter-regional basis are
      envisioned.

PMID- 19585873
TI  - [Geographic epidemiologic descriptive study on the national priority site for
      remediation "Laguna di Grado e Marano"].
AB  - OBJECTIVE: to describe the mortality profile of the population resident in the
      polluted area of national concern (SIN) "Laguna di Grado e Marano" Friuli-Venezia
      Giulia region, in the period 1997-2001 and to examine mortality temporal trends
      between 1981 and 2001. DESIGN: a small-area epidemiological study based on
      descriptive statistics, socioeconomic deprivation variables, analysis of spatial
      heterogeneity disease mapping and time trend analysis was carried out. MAIN
      OUTCOME MEASURES: age-standardised rate, standardised mortality ratios (SMRs),
      SMRs adjusted by socioeconomic deprivation, spatial heterogeneity test results,
      empirical and hierarchical Bayesian estimators, and temporal trends of selected
      causes are shown. RESULTS: compared to regional averages, SMRs in the SIN were
      significantly higher for lung (25.3%) and stomach (54.1%) cancer in men and for
      ovarian cancer (82.6%) in women. SMRs were instead significantly lower for all
      causes of death (8.7%), respiratory (26.6%) and cardiovascular (13.7%) diseases,
      liver (51.3%) and pancreas (46.9%) cancer in men and for cardiovascular diseases
      (22.1%) in women. These results did not change after adjustment by socioeconomic
      status. Spatial distribution of risks was homogeneous among municipalities and no
      groups of high risk municipalities were identified. A significant increasing
      temporal trend was observed for ovarian cancer. CONCLUSION: following these
      results, we suggest to carry out a cohort incidence and mortality study to verify
      the potential role of occupational exposures on cancer mortality in men. We also
      recommend an in depth analysis in women to clarify the role of potential iron
      replacement by pollutants, such as cadmium and lead that are present in the area.

PMID- 19585874
TI  - [Statistical analysis of the incidence of some cancers in the province of Taranto
      1999-2001].
AB  - OBJECTIVE: to estimate the spatial distribution of risk, in order to assess its
      correlation to environmental pollution exposure around the large production
      facilities located in the Taranto area, and to identify high risk areas not
      previously reported. SETTING: Italy, Taranto province (581,508 inhabitants).
      DESIGN: incidence data in 29 municipalities of the Taranto province were
      extracted from the Jonico Salentino Cancer Registry (RTJS) for the following
      cancer sites: lung (ICDX C33-C34); pleura, pleuric mesothelioma (ICDX C45.0);
      bladder, malignancies only (ICDX C67); brain (ICDX C70-72); non-Hodgkin lymphoma
      (ICDX C82-85, C96); leukaemia (ICDX C91-5). Age standardized incidence rates for
      the whole province were computed. High-level risk areas were classified using a
      Poisson model, computing area-specific p-values associated to the null hypothesis
      of no increased risk (i.e. relative risk equal to 1). A hierarchical spatial
      Bayesian model was estimated to strengthen results: specifically two additional
      variance components, accounting for relative risk spatial autocorrelation and
      excess heterogeneity respectively, were considered in the model specification.
      Bayesian mapping of disease incidence allows for the drawing of regularized
      (smoothed) maps. To adjust for the effect of socio-economic deprivation, a five
      variable index was introduced into the model as an ecological covariate. RESULTS:
      an increased risk of lung, pleura and bladder cancer was observed among male
      residents in the city of Taranto (respectively: SIR 1.24, p-value < 0.01; SIR:
      2.21, p-value < 0.01; SIR 1.28, p-value < 0.01). For non-Hodgkin lymphoma, a
      significant value was observed in the city of Taranto for males (SIR 1.46, p
      value < 0.01), as well as in the neighbouring area of Pulsano for females (SIR
      3.88, p-value < 0.01). An unexpected increased risk of brain cancer was found in
      both sexe risk (especially among males) of lung, pleura and bladder cancer is
      likely related to the chemical pollutants and asbestos, due to the presence of
      many industries and shipyards in the city of Taranto.

PMID- 19585875
TI  - [Skin cancer risk factors in childhood: findings of a survey in an Italian area
      characterized by atypical migration].
AB  - OBJECTIVE: to evaluate the association of different phenotypes with sun
      sensitivity factors, sun protection behavior and ethnicity in school-age
      children. DESIGN: cross sectional study in the framework of a survey of children
      using a self-administered questionnaire. SETTING AND PARTICIPANTS: 35412 children
      attending primary schools in the provinces of Latina and Rome, located in the
      Lazio region (Italy), in the 1998-2001 time period. MAIN OUTCOME MEASURES: Odds
      Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) computed
      through univariate and multivariate logistic regression models. RESULTS: "FOTO
      positive" phenotype, a proxy variable of the fair phenotype, was directly and
      significantly associated with the tendency to sunburn (OR 4.64; 95% CI 4.39
      4.89), the presence of freckles on the face (OR 1.65; 95% CI 1.55-1.77), of naevi
      on the left forearm (OR 1.18; 95% CI 1.12-1.25), the number of grandparents born
      in northern areas (OR 1.54; 95% CI 1.15-2.07, for four northern grandparents
      versus none), the residence in Latina Province (OR 1.13; 95% CI 1.07-1.20) and
      the use of sunscreens (OR 1.70; 95% CI 1.55-1.88). An inverse association was
      observed with the male sex (OR 0.91; 95% CI 0.86-0.96), the increase of school
      class level (OR 0.66; 95% CI 0.61-0.72, for the highest versus the lowest school
      class level) and the ability to tan (OR 0.38; 95% CI 0.34-0.42). CONCLUSION:
      These findings confirmed that fairness of phenotype is associated in children
      with other skin cancer risk factors as well as ethnicity and parents' sun
      protection behavior.

PMID- 19585876
TI  - [Amyotrophic lateral sclerosis and soccer: what possible relationship between the
      city magistrate and the scientific community?].

PMID- 19585877
TI  - [Petrochemical industry and health risk perception: a research carried out by
      means of focus groups].
AB  - This paper discusses the results of a qualitative analysis aimed at collecting
      new and useful elements for a questionnaire prepared to be submitted to a
      representative sample of the population residing in the industrial areas of
      Sicily. The study employed four focus groups and addressed adults selected among
      the population living in the area called Valle del Mela (Sicily) in order to
      investigate customs, images and perception of risks related to living conditions
      in a complex industrial area. The area under investigation is characterized by
      the presence of a large refinery process plants, a power plant and a number of
      small factories operating in various highly polluting sectors. The study
      investigates the specific perceptions expressed by conveyed people according to
      their sex, age and parental status. The authors suggest that their findings are
      useful in order to implement communication actions aimed at targeting broader
      strata of the local population.

PMID- 19585878
TI  - [Asbestos import in Italy: the transit through Livorno harbour from 1957 to
      1995].
AB  - This work aims to describe quantities, type of packaging and geographical area of
      origin of the asbestos fibres unloaded in Livorno harbour between 1957 and 1995.
      Historical data, available for this period, were collected from Il Messaggero
      Marittimo, a periodical journal dealing with Livorno harbour activities.
      Collaboration between the local Health and Safety Unit (ASL 6) and the Institute
      for Study and Prevention of Cancer (ISPO), both Regional Institutions of the
      National Health Service, made it possible to carry out this work. The computation
      of the collected data for the whole period allows the description of the
      quantities, year by year and the assessment of the percentage imported through
      Livorno on the total tonnage imported in Italy during the same period. The
      detection of the geographical areas of origin allowed to estimate the quantities
      subdivided by type of fibre (serpentine/amphiboles). These results will help the
      historical assessment of occupational asbestos exposure of the Livorno dockers.

PMID- 19585879
TI  - [Italy. The seven tumors with the worst prognosis].

PMID- 19585880
TI  - [Risk assessment in root canal therapy].
AB  - The aim of endodontic therapy is the prevention or treatment of apical
      periodontitis. Some years ago, 2 endodontic classification systems, the Dutch
      Endodontic Treatment Index (DETI) and the Endodontic Treatment Classification
      (ETC), were introduced in the Netherlands. These systems differentiate between
      complicated and uncomplicated endodontic cases. Before treatment, the systems may
      help in assessing the difficulties and risks of performing an endodontic
      treatment and in deciding whether to carry out treatment or refer the patient to
      an endodontist. Root canal therapy may involve considerable risks. This is
      illustrated with three clinical cases, which show the sort of complications that
      may be prevented using the 2 classification systems.

PMID- 19585881
TI  - [Cariology and restorative dentistry: old and new risks].
AB  - Complaints concerning restorative treatments at disciplinary tribunals are
      relatively rare. The nature of the complaints, the judgements, and the implicit
      view on caries management are, however, a cause of concern. Usually, the
      complaints are on alleged negligence because lesions were not or were too late
      restored. Modern caries management concentrating on disease control rather than
      on damage repair and its minimally invasive nature could be reasons of complaints
      concerning perceived negligence. As usual, careful documentation of findings,
      diagnostics, risk assessment, and monitoring decisions and good patient
      communication are decisive in preventing complaints. However, post-graduate
      education of dentists in caries detection, diagnosis, and management is needed to
      reduce the variability of caries care provided.

PMID- 19585882
TI  - [Complications and failures in dentoalveolar surgery].
AB  - Complications and failures are unavoidable in dentoalveolar surgery, but can be
      reduced if treatment is carried out in the proper manner. Yet, one has to accept
      a certain percentage of complications and failures and the patient should be
      informed about that prior to surgery. Complications become reproachable when
      insufficient diagnostic procedures have been carried out or when surgery has not
      been performed in the proper fashion. Insufficient prior information, even in
      cases of referral, must be seen as reproachable practice, especially in the
      context of the Law on Medical Treatment Agreement.

PMID- 19585883
TI  - [Risks of orthodontic treatment].
AB  - Risks of orthodontic treatment identified in the literature are: enamel damage,
      root resorption, periodontal damage, temporomandibular disorders, tooth
      devitalization, treatment failure, and relapse. Enamel damage in the form of
      irreversible demineralization can take place during treatment with fixed
      appliances in the absence of adequate oral hygiene. Root resorption occurs, but
      seldom to the point of clinical relevance. Individual susceptibility and genetics
      are determining factors. Periodontal damage occurs as gingival recessions.
      Temporomandibular disorders and tooth devitalization hardly occur. Treatment
      failure is related to the assessed pre-treatment goals and dependent on the
      knowledge and skills of the care provider, patient-cooperation, and factors
      beyond anyone's control. Relapse is a common feature, but does not constitute a
      treatment risk. The greatest risk is a failure to adequately inform the patient
      concerning all of the (im)possibilities and their consequences.

PMID- 19585884
TI  - [Pitfalls in diagnosis and treatment of periodontal diseases].
AB  - In the present article the complex aetiology of periodontal diseases is
      explained. Furthermore risk factors are identified for making mistakes in
      diagnosis and failing treatment of periodontal infections. This includes patient
      and treatment factors such as incomplete anamnesis, improper screening and
      documentation as well as insufficient plaque and smoking control, improper use of
      antibiotics and insufficient pocket-elimination and maintenance care. The use of
      a strict diagnostic and treatment protocol including evaluation is emphasized in
      order to obtain optimal treatment results. Patients should minimally expect to be
      regularly screened by their dentist or dental hygienist for periodontal diseases,
      to be informed about the further diagnostic steps and possible treatment options
      and to get periodontal care organised. Providers of oral health care can, in this
      way, reduce the risk of negligent practice and significantly limit their
      liability.

PMID- 19585885
TI  - [Risks of dental fear reduction treatments].
AB  - In dentistry, estimations of the risk of failure of treatments focused on dental
      fear reduction are particularly high (about 60%). Research data on this subject
      are lacking. Failure has been defined as a treatment whose aim, sufficient
      reduction of fear to make possible treatment in a general dental practice, has
      not been achieved. Nine different types of risk may be the cause of a treatment
      failure: insufficient motivation, fear greater than the capacity to cope with it,
      co-morbidity, trouble with entering into a patient-care provider relation,
      inaccurate treatment indication or treatment strategy, patient too dependent on
      care provider, treatment insufficiently fulfilling demand, damage to the patient
      care provider relation, and accident during treatment.

PMID- 19585886
TI  - [Haematopoietic stem cell transplantation and oral complications].
AB  - New haematopoietic stem cell transplantation procedures make the treatment
      available to patients who previously did not qualify, such as the elderly. In
      addition, the spectrum of oral complications associated with haematopoietic stem
      cell transplantation has altered as a result of the recent developments. This
      article is a review of the main principles of haematopoietic stem cell
      transplantation and provides information on oral complications which may develop,
      such as mucositis, infections, bleeding, graft-versus-host disease, xerostomia,
      hyposalivation, altered taste, secondary tumors, osteoporosis, osteonecrosis and
      growing and developing disturbancies. Finally, the role of dental care providers
      in cases of haematopoietic stem cell transplantation is addressed.

PMID- 19585887
TI  - Mapping sleeping sickness in Western Africa in a context of demographic
      transition and climate change.
AB  - Human population growth, climate change and economic development are causing
      major environmental modifications in Western Africa, which will have important
      repercussions on the epidemiology of sleeping sickness. A new initiative, the
      Atlas of human African trypanosomiasis (HAT), aims at assembling and geo
      referencing all epidemiological data derived from both active screening
      activities and passive surveillance. A geographic database enables to generate up
      to-date disease maps at a range of scales and of unprecedented spatial accuracy.
      We present preliminary results for seven West African countries (Benin, Burkina
      Faso, Cote d'Ivoire, Ghana, Guinea, Mali and Togo) and briefly discuss the
      relevance of the Atlas for future monitoring, control and research activities.

PMID- 19585888
TI  - [Two new species of Dasypsyllus (Siphonaptera: Ceratophyllidae) from Chile].
AB  - New taxa, known only by the male, are added to chilio-andean fauna. These fleas
      belong to sub-genus Neornipsyllus, parasites of Birds, essentially
      "Passeriforms". D. (N.) huinayensis sp. n. is, inter alia, characterized by the
      place of large setae on telomere; D. (N.) tapaculensis sp. n. show a tergit XI
      (or proctiger) unusual for the entire Order by the form and the chaetotaxy
      composed, essentially, of forked setae.

PMID- 19585889
TI  - Reappraisal of the specific status of Rhabdias (Nematoda: Rhabdiasoidea) from
      Malagasy chameleons in the Paris museum collection.
AB  - To date Rhabdias gemellipara is the only species described from Malagasy
      chameleons, but heterogeneity of the material had been suspected. 11 samples of
      Rhabdias parasites present in the Paris Natural History Museum collection were
      examined. The size and shape of the buccal capsule, shape and length of the
      oesophagus, shape of the apical region of the intestine, extent of the genital
      tract and structure of the cuticular vesicle led to the distinction of five
      species. Rhabdias rabetafikae n. sp. parasitises Columma cucullatum in the
      northeastern region (Cap Machoual). In the eastern region, R. nasutum n. sp. is
      parasitic in C. nasutum, and R. brevicorne n. sp. in C. brevicorne. All three
      species are similar in size to the African species parasitic in chameleons from
      which they can be distinguished by several characters. The small species, R.
      gemellipara, type host C. parsonii from the eastern region, was also found in C.
      brevicorne from the same geographic region. In the central region, Rhabdias sp.,
      equally collected from C. brevicorne, is distinguished from R. gemellipara by a
      laterally flattened buccal capsule. All Malagasy species are hermaphrodites.
      Throughout the worm's life spermatozoids are formed intermittently in a band of
      cells situated at 1-2 mm from the extremity of the ovaries; they migrate in the
      ovaries and accumulate in the oviducts.

PMID- 19585890
TI  - Evaluation of speed and duration of efficacy of spinosad tablets for treatment
      and control of Ctenocephalides canis (Siphonaptera: Pulicidae) infestations in
      dogs.
AB  - A controlled clinical trial was performed to determine the duration of efficacy
      of a new oral insecticide formulation of spinosad for the control of
      experimentally induced Ctenocephalides canis infestations in dogs. Twelve Beagle
      dogs (two groups of six) were used in the study. Dogs in the treated group
      received spinosad tablets per os on D0 at the commercial dosage. All dogs were
      infested with 100 fleas on Days - 7, - 1, 7, 14, 21, 28 and 35. The dogs were
      combed four hours after each infestation and fleas were counted and replaced on
      the coat. 24 hours after each infestation fleas were combed, counted and removed.
      The efficacy of the formulation was calculated four and 24 hours after the
      treatment and then four and 24 hours after each new infestation. The mean number
      of fleas on the control dogs was respectively between 65.1 and 83.3 at four hour
      counts and between 58.3 and 75.3 at 24 hour counts. The product was well
      tolerated. The treatment controlled the fleas already present on the skin with
      81% efficacy at four hours and 100% efficacy at 24 hours. For the weekly
      infestations, the speed of action of the product was high: at four hours the
      efficacy was 100% at D7, 96% at D14, 74% at D21, 42% at D28, 12.90% at D35 and
      12.8% at D42. The efficacy evaluated 24 hours after each infestation was
      approximately 100% during three weeks then 90% at D39, 81.4% at D36 and 80.4% at
      D43. A single dose of the new spinosad tablet formulation should control flea
      populations in dogs for four weeks as indicated in the claim (evaluation
      performed at 48 h for the registration). Spinosad tablet is the first product
      administered per os which acts so long and so quickly against adult fleas.

PMID- 19585891
TI  - Efficacy of six-dose regimen of artemether-lumefantrine for the treatment of
      uncomplicated falciparum malaria, three years after its introduction into
      Ethiopia.
AB  - We assessed the clinical and parasitological efficacy of six-dose regimen of
      artemether-lumefantrine (AL) (Coartem) for treating uncomplicated P. falciparum
      malaria three years after its introduction into Ethiopia. A total of 102 patients
      (mean age: 15.7 years; age range: 1-50 years) were enrolled in the study and
      followed-up for 28 days based on WHO protocol. Treatment with AL resulted in 100%
      adequate clinical and parasitological response (ACPR). No severe side-effect of
      the drug was observed. All patients had rapid clinical and parasitological
      responses. None of the subject was found to be positive for asexual or sexual
      stage of the parasite after day 3. A significant increase in the mean of
      haemoglobin level was observed on day 28 posttreatment (11.4 g/dL on day 0 vs
      12.3 g/dL on day 28, p < 0.05). Thus, artemisinin-based combination therapies
      (ACTs) seem to mitigate not only the problem of drug resistance malaria but also
      the transmission of the disease. Nevertheless, monitoring ACT therapeutic
      efficacy is crucial in Ethiopia.

PMID- 19585892
TI  - Establishment of a continuous culture system for Entamoeba muris and analysis of
      the small subunit rRNA gene.
AB  - We established a culture system for Entamoeba muris (MG-EM-01 strain isolated
      from a Mongolian gerbil) using a modified Balamuth's egg yolk infusion medium
      supplemented with 4% adult bovine serum and Bacteroides fragilis cocultured with
      Escherichia coli. Further, encystation was observed in the culture medium. The
      morphological characteristics of E. muris are similar to those of Entamoeba coli
      (E. coli); moreover, the malic isoenzyme electrophoretic band, which shows
      species-specific electrophoretic mobility, of E. muris had almost the same
      mobility as that observed with the malic isoenzyme electrophorectic band of E.
      coli (UZG-EC-01 strain isolated from a gorilla). We determined the small subunit
      rRNA (SSU-rRNA) gene sequence of the MG-EM-01 strain, and this sequence was
      observed to show 82.7% homology with that of the UZG-EC-01 strain. Further, the
      resultant phylogenetic tree for molecular taxonomy based on the SSU-rRNA genes of
      the 21 strains of the intestinal parasitic amoeba species indicated that the MG
      EM-01 strain was most closely related to E. coli.

PMID- 19585893
TI  - Epidemiology and effects of gastrointestinal nematode infection on milk
      productions of dairy ewes.
AB  - 66 Pampinta breed ewes were studied during milking to evaluate the infection and
      the effect of gastrointestinal nematode on milk production sheep system.
      Naturally infected ewes on pasture were randomly allocated to two groups: TG,
      suppressively treated group every four weeks with levamisole and UG, untreated
      group. Faecal nematode egg counts and larval differentiation were conducted
      monthly. Successive groups of worm free tracer lambs were grazed with ewes and
      then slaughtered for worm counts. Test-day milk yield of individual ewes was
      recorded and ewe machine-milking period length (MPL) were estimated. Faecal egg
      counts and tracer nematode numbers increased towards midsummer and declined
      sharply toward the end of the study. TG (188.0 +/- 60 liters) produced more (p <
      0.066) milk liters than UG (171.9 +/- 52.2) and TG had significantly more
      extended (p < 0.041) MPL than those of UG. The present study showed that dairy
      sheep were negatively affected by worms, even when exposed to short periods of
      high acute nematode (mainly Haemonchus contortus) infection.

PMID- 19585894
TI  - [Entomological investigation following the re-emergence of yellow fever in 2008
      in Abidjan area (Cote d'Ivoire)].
AB  - In April 2008, Abidjan was again faced with another case of yellow fever after
      the epidemic of 2001 causing mass immunization campaign. In order to evaluate the
      extent of amaril virus circulation and the risk for local people, an
      entomological investigation was carried out by the Ministry of Health and Public
      Hygiene of Cote d'Ivoire. At "Entent" area of Treichville, Breteau index was
      estimated at 34, recipient index at 20% and house index at 25%. Those indexes
      were respectively 53, 21 and 31% at "Vridi canal" of Port Bouet. In the both
      neighborhood, Aedes aegypti accounted for more than 80% of mosquitoes caught and
      more than 90% of mosquitoes adults obtained from larval breeding. This new
      situation of epidemic risk could be explained by several factors including the
      reception of 70% of forced migration people caused by the crisis in the country
      occurred in 2002, the probable drop of preventive immunization, the environment
      deterioration creating of more breeding sites of Ae. aegypti.

PMID- 19585895
TI  - [Spatial variation of risk for pigs to contract trypanosomosis in farms situated
      in the peri-urban area of Kinshasa].
AB  - In an effort to understand better the transmission risk as well for the animal
      African trypanosomosis (AAT) as for the human trypanosomosis (HAT) in the peri
      urban zone of Kinshasa, a serologic study was carried out in local pig farms from
      2003 to 2005. An indirect ELISA was used to detect the presence of trypanosome
      antibodies in 1,240 pigs originating from 404 farms. Seropositivity was recorded
      in 155 farms (38%), but varied considerably according to the district. In 6% of
      the farms TAA could be confirmed by parasitological examination. Trapping sites
      (n = 367) established in the neighbourhood of pig farms made it possible to
      capture 1,935 tsetse flies (Glossina fuscipes quanzensis). Among 562 dissected
      flies 23 were found to harbour trypanosomes resulting in an infection rate of
      4.1%. In the majority of the districts the transmission risk for animal
      trypanosomosis anticipated from the apparent vector densities was corroborated by
      the serology. Zones with strong indications of local AAT transmission were
      identified in several quarters of three peri-urban districts of Kinshasa: Mount
      Ngafula, Ngaliema and N'Sele. An intensification of tsetse control activities in
      those sites of increased transmission risk is essential.

PMID- 19585896
TI  - Apparent pseudoparasitism of the alimentary canal of a 5-year-old child by the
      millipede Brachyiulus lusitanus (Diplopoda: Julidae).

PMID- 19585897
TI  - Increased screening for osteoporosis.

PMID- 19585898
TI  - The economics of fragility fractures in West Virginia.
AB  - Compared to the United States, West Virginia has a higher proportion of residents
      aged 60 or older. This situation creates a stronger risk factor for osteoporosis
      and subsequent fragility fractures. The widespread availability of bone
      densitometry screening to identify osteoporosis and the marketing of effective
      agents to reduce fractures in the past decade has resulted in cost savings. We
      estimated the absolute number of fragility fractures associated with osteoporosis
      in West Virginia and projected their costs over a 5-year period. Cost savings
      were based on the variables of the proportion of osteoporotic patients identified
      and their long-term adherence to prescribed calcium,vitamin D, and bisphosphonate
      therapy. Our results indicate that only a small amount of potential cost savings
      (varying between less than 0.5% to 3.0%) is currently realized through diagnosis
      and adherence to prescribed treatment. We conclude that increased screening and
      recognition of osteoporosis by the primary care provider is a more feasible
      strategy to improve cost savings and fracture reduction rather than attempts to
      improve treatment adherence.

PMID- 19585899
TI  - Severe coronary tortuosity and the relationship to significant coronary artery
      disease.
AB  - Severe coronary artery tortuosity on coronary angiogram has not been previously
      evaluated to determine whether it is associated with coronary artery disease or
      risk factors for coronary artery disease. A retrospective analysis of all
      patients who underwent coronary angiography at West Virginia University Hospital
      during an eight month period was performed. All patients with severe coronary
      tortuosity (SCT), defined as two consecutive 180 degrees turns by visual
      estimation in a major epicardial artery, were identified and their medical
      records reviewed for the presence of coronary artery disease risk factors and
      presence of significant coronary artery disease. A randomly chosen group of
      patients who underwent coronary angiography during the same time who did not have
      SCT was used for a control group. Multivariable analysis using logistic
      regression was performed to determine predictors of SCT. Severe coronary
      tortuosity was found in 12.45% of our 1221 patients. Female gender was found to
      be significantly higher in the tortuosity group of patients compared to the
      control group (p = 0.039). The presence of severe tortuosity was associated with
      a statistically significant lower incidence of significant coronary artery
      disease (p = 0.003). Hypertension, hyperlipidemia, smoking, family history of
      coronary artery disease, diabetes mellitus, and age > or =65 years were not
      predictors of SCT. Our study did not find that coronary artery disease risk
      factors were predictors of coronary tortuosity. Future investigations may provide
      further insight into the significance or cause of coronary artery tortuosity.

PMID- 19585900
TI  - Does sex make a difference in survival of patients undergoing resection for early
      stage non-small cell lung cancer (NSCLC)?
AB  - OBJECTIVE: To determine if sex associated differences exist in presentation and
      survival of patients undergoing resection for early stage nonsmall cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Retrospective review of 2207 patients with
      Surveillance, Epidemiology, and End Results (SEER) Summary Stage I, II or III
      (local or regional disease) patients eligible for surgery, nonsmall cell lung
      cancer diagnosed and treated in WV between 1993 and 2000, which underwent surgery
      as a first course of treatment. Data set obtained from the West Virginia Cancer
      Registry. RESULTS: 1332 male cases and 875 female cases were reviewed. No
      statistically significant difference was found with mean age of diagnosis (men
      66.5 years; women 67.2 years). A greater proportion of women had adenocarcinoma
      (p < 0.0001), lower grade (p = 0.002), and lower SEER summary stage (p = 0.009).
      There was no difference in laterality of tumor, 30-day post surgery survival or
      surgical procedure between men and women. Regression analysis showed a higher
      hazard ratio was associated with a increasing stage, grade, and those > or =65
      years of age while lower hazard ratio was associated with adenocarcinoma.
      CONCLUSIONS: This study found that stage, grade, age, and histology, but not sex
      was the significant prognostic indicators of death in five years.

PMID- 19585901
TI  - Familial Hurthle cell carcinoma of the thyroid: case reports and review of the
      literature.
AB  - OBJECTIVE: To describe case reports of a brother and sister pair with Hurthle
      cell carcinoma of thyroid. METHODS: The clinical presentation, diagnostic workup,
      treatment and clinical course of HCC is described for both patients. Relevant
      family history is discussed. This is followed by a review of literature regarding
      genetic basis of familial and sporadic HCC. RESULTS: Both cases have striking
      similarities in their presentation and disease progression. Both had the disease
      diagnosed in later years of life, had cold nodules for 4-5 years before
      histological diagnosis, and both had local recurrence following thyroidectomy and
      postoperative radioiodine ablation. Local recurrence was treated with external
      radiation in each patient and both of them had persistent elevation of serum
      thyroglobulin levels with negative diagnostic whole body I-131 scans. Later on
      pulmonary metastatic disease was documented in each patient. Family history was
      pertinent for benign nodular thyroid disease in multiple family members.
      CONCLUSION: HCC is a rare malignancy of thyroid. Genetic basis of familial HCC
      remains to be elucidated. Our case describes a rare familial occurrence of this
      malignancy and highlights the importance of obtaining a careful family history in
      management and surveillance of thyroid cancer.

PMID- 19585902
TI  - Elevated cardiac troponins in sepsis: what do they signify?
AB  - Serum troponins are sensitive markers used to diagnose acute coronary syndrome in
      association with signs and symptoms of chest pain and EKG changes. Cardiac
      troponins are elevated in 85% of patients with sepsis in the absence of acute
      coronary syndrome. Small studies have shown that elevated troponin levels
      identify patients with sepsis who are at increased risk of mortality. The purpose
      of this study was to (1) identify the outcome of cardiac troponin positive sepsis
      patients in our hospital, (2) determine whether the traditional cardiac risk
      factors predispose septic patients for positive troponin and (3) evaluate the
      cardiac interventions done for troponin positive patients. CONCLUSION: In our
      study, patients with elevated troponins had a higher mortality. Hypertension
      (HTN) and Coronary Artery Disease (CAD) increased the risk of mortality in
      troponin positive patients. Several interventions were performed including
      medications, echocardiogram, and cardiology consultation. Treatment medications
      did not improve mortality rates.

PMID- 19585903
TI  - West Virginia State Trauma & Emergency Care System begins implementation of EMS
      data system.

PMID- 19585904
TI  - [Dinitrogen monoxide in the treatment of labor pains].
AB  - Self-administered nitrous oxide relieves labour pain in approximately two-thirds
      of women, and there is a dose-response with a maximum effect at a concentration
      of 70%. Nitrous oxide can be used during all stages of labour, and it has no
      impact on the progress of labour. Occupational exposure of health care workers to
      nitrous oxide has no adverse effects on their reproductive health if there is an
      adequate scavenging system in the delivery rooms. The greenhouse effect of the
      medical use of nitrous oxide is minimal and in future, its catalytic splitting to
      nitrogen and oxygen may overcome this adverse effect.

PMID- 19585905
TI  - [Phenylketonuria].
AB  - Owing to our special genetic heritage, phenylketonuria is very rare in Finland,
      but the situation will change as the number of immigrants from populations with a
      larger incidence increases. In persons with this disorder, the enzyme
      phenylalanine hydroxylase, which metabolizes phenylalanine to tyrosine, is not
      functioning normally, leading to the accumulation phenylalanine within the body.
      High levels of phenylalanine are toxic to the central nervous system. A newborn
      affected with phenylketonuria is asymptomatic but will rapidly become disabled
      without therapy. The leading principle of the therapy is careful limitation of
      phenylalanine intake.

PMID- 19585906
TI  - [When should secondary hypertension be suspected?].
AB  - Secondary hypertension is diagnosed in 5 to 10% of hypertensive patients. The
      probability of secondary hypertension increases, if the screening is focused on
      patients in which even a combination of three medicaments fails to attain the
      therapeutic objective, i.e. the so-called treatment-resistant hypertensives.
      Exclusion of secondary hypertension is part of the analysis of treatment
      resistant hypertension. The most common causes of secondary hypertension are
      renal diseases, renal artery stenosis and primary hyperaldosteronism.

PMID- 19585907
TI  - [Diagnosis and therapy of male hormonal changes related to aging].
AB  - The most common male hormonal change related to aging is the decrease of
      testosterone production by the testicle. It is, however, subject to large
      individual variation and the testicular hormonal function remains normal in the
      majority of aging men. It is important that the attending physician can reliably
      diagnose the need for testosterone replacement therapy, is aware of alternative
      forms of therapy, and recognizes the actual effects and risk factors of hormone
      replacement therapy.

PMID- 19585908
TI  - [Male osteoporosis].
AB  - Osteoporotic fractures in men are associated with considerable morbidity and
      mortality. Incidence of fractures increases with age. Hormonal changes associated
      with ageing predispose to osteoporosis also in men, although secondary causes in
      the pathogenesis of osteoporosis become more pronounced. Accordingly, these
      should always be excluded before osteoporosis can be considered age-related or
      idiopathic. Prevention and basic care of osteoporosis include adequate supply of
      calcium and vitamin D, increase in physical activity and cessation of smoking.
      Bisphosphonates, calcitonin and teriparatide are applicable drugs for male
      osteoporosis.

PMID- 19585909
TI  - [Sexuality and sexual disorders of aging man].
AB  - Functional ability of an aging man decreases less than presumed, and sexual
      desire remains for long. The most common disturbances include lessened ability
      for erection and ejaculatory disturbances. Some men will be helped for their
      sexual disturbances in connection with the treatment of urinary symptoms caused
      by benign prostatic hyperplasia. Erectile dysfunction may be the initial symptom
      of cardiovascular disease. Erectile dysfunction may also be caused by medication
      used by the patient. If an aged man wants therapy for his sexual disorder, he
      should be individually provided with the most appropriate treatment form.

PMID- 19585910
TI  - [Male aspect towards good aging].
AB  - Columnist "Kirsti" of Helsingin Sanomat newspaper divided middle age into three
      stages: early middle age (35-45 years), mid-middle age (45-55) and late middle
      age (55-65). Similarly, those at 65-75 are living juvenile old age, those at 75
      85 midlife old age and those over 85, senescent old age. Classification of these
      ages according to the years of life does, however, not correspond with personal
      feelings. The intrinsic relation to life and death may provide a better
      definition of the stages of life. At the middle age we become aware of the
      limitation of life and begin to count the remaining years.

PMID- 19585911
TI  - Leakage of teeth root-filled with GuttaFlow and a single GP cone compared to
      lateral condensation and warm vertical condensation.
AB  - INTRODUCTION: Root canal obturation can be time consuming and complicated.
      GuttaFlow is suggested for use with a simple, single cone obturating technique.
      AIMS AND OBJECTIVES: The aim of this study was to evaluate whether GuttaFlow and
      a single GP cone would produce an effective seal. METHODS: Three experimental
      groups were used. Group one was obturated with GP using lateral condensation,
      group two with GP using vertical condensation and group three using GuttaFlow and
      a single GP cone. Bacterial micro-leakage was tested using the two-chamber
      method, followed by dye penetration testing. Data was subjected to statistical
      analysis using the Chi Square test. RESULTS: There was no significant difference
      between GP using lateral condensation and GuttaFlow using a single cone for
      bacteria (p=0.8989) or dye (p=0.7489). GP using lateral condensation performed
      better than GP using vertical condensation for bacteria (p=0.0003) and dye
      (p=0.0006). GuttaFlow using a single cone also performed better than GP using
      vertical condensation for bacteria (p=0.0003) and dye (p=0.0004). CONCLUSIONS:
      The micro-leakage of GuttaFlow using a single cone technique is similar to that
      of GP using lateral condensation and less than that of GP using vertical
      condensation as used in this study.

PMID- 19585912
TI  - The influence of powder liquid ratio on the flexural strength of fibre reinforced
      acrylic resin material.
AB  - INTRODUCTION: Often the powder liquid (P/L) ratio of polymethyl methacrylate
      (PMMA) resins is changed to modify the handling properties of the material. While
      it is known that this may influence the mechanical properties of unreinforced
      PMMA resin, little is known about its effect on fibre reinforced resin. PURPOSE:
      The purpose of this study was to determine how different P/L ratios influence the
      flexural strength (FS) of a glass fibre reinforced autopolymerizing PMMA resin
      used for fabricating fixed partial dentures. METHODS: Two main groups of PMMA
      resin, 1 unreinforced and 1 reinforced with glass fibre, had 3 subgroups (n=21)
      each representing a different P/L ratio. The manufacturer's recommended ratio
      served as control. The specimens were prepared for a 3-point bending test. Using
      a universal testing machine, maximum force was recorded and the FS was
      calculated. Median FS values were compared by means of non-parametric analysis of
      variance (Kruskal-Wallis). A p-value of less than 0.05 was considered
      significant. RESULTS: FS values of all reinforced subgroups were significantly
      higher than the values of the unreinforced subgroups (p<0.05). Among the 3
      unreinforced subgroups the difference in FS was insignificant (p>0.05). Within
      the reinforced group there was a significant difference between the control
      group, which had a higher median FS value than the two other subgroups (p<0.05).
      CONCLUSION: When reinforcing PMMA resin with glass fibre, it is important to use
      the recommended P/L ratio. For unreinforced PMMA resin the P/L ratio can be
      changed within limits without adverse effects on the FS.

PMID- 19585913
TI  - The orthodontic management of a patient presenting with cemento-osseous
      dysplasia.
AB  - Cemento-osseous dysplasias are sometimes seen on routine radiographic examination
      of the tooth-bearing areas of the jaws, most commonly amongst adult female
      patients. Lesions present as radiolucent to radio-opaque areas, depending on
      various levels of maturity. Extraction of teeth is strongly contraindicated
      because there is a high risk of infection with a possibility of bone
      sequestration, as antibiotics are unable to cross the thick cortical marginal
      bone that surrounds these lesions. No report has been found in the literature on
      the orthodontic management of patients with this condition. This paper reports on
      a 28-year-old black female patient with cemento-osseous dysplasia who received
      orthodontic treatment.

PMID- 19585914
TI  - General practitioner's radiology case 72. Torus palatinus and torus mandibularis.

PMID- 19585915
TI  - Sedation corner 31. Hardware needed--the equipment that must be in the bag (kit)
      when the sedationist visits you.

PMID- 19585916
TI  - Oral medicine case book 16. Amalgam tattoos.

PMID- 19585917
TI  - Treatment planning in the anterior maxilla (part 1).

PMID- 19585918
TI  - Creating a segregated medical profession: African American physicians and
      organized medicine, 1846-1910.
AB  - An independent panel of experts, convened by the American Medical Association
      (AMA) Institute for Ethics, analyzed the roots of the racial divide within
      American medical organizations. In this, the first of a 2-part report, we
      describe 2 watershed moments that helped institutionalize the racial divide. The
      first occurred in the 1870s, when 2 medical societies from Washington, DC, sent
      rival delegations to the AMA's national meetings: an all-white delegation from a
      medical society that the US courts and Congress had formally censured for
      discriminating against black physicians; and an integrated delegation from a
      medical society led by physicians from Howard University. Through parliamentary
      maneuvers and variable enforcement of credentialing standards, the integrated
      delegation was twice excluded from the AMA's meetings, while the all-white
      society's delegations were admitted. AMA leaders then voted to devolve the power
      to select delegates to state societies, thereby accepting segregation in
      constituent societies and forcing African American physicians to create their
      own, separate organizations. A second watershed involved AMA-promoted educational
      reforms, including the 1910 Flexner report. Straightforwardly applied, the
      report's population-based criterion for determining the need for phySicians would
      have recommended increased training of African American physicians to serve the
      approximately 9 million African Americans in the segregated south. Instead, the
      report recommended closing all but 2 African American medical schools, helping to
      cement in place an African American educational system that was separate,
      unequal, and destined to be insufficient to the needs of African Americans
      nationwide.

PMID- 19585919
TI  - Segregation, civil rights, and health disparities: the legacy of African American
      physicians and organized medicine, 1910-1968.
AB  - Between 1910 and 1968, the National Medical Association (NMA) repeatedly clashed
      with the American Medical Association (AMA) over the latter organization's racial
      bars to membership and other health policy issues. The NMA, founded in 1895 as a
      nonexclusionary medical society to provide a voice for disenfranchised black
      physicians and patients, struggled in its early years, during which AMA
      leadership took scant notice of it. But skirmishes ensued over such actions as
      stigmatizing racial labels in the AMA's American Medical Directory, which,
      beginning in 1906, listed all U.S. physicians but designated African Americans
      with the notation col. The NMA also repeatedly asked the AMA to take action
      against overt racial bars on blacks' membership in its constituent state and
      county societies. During the civil rights era, African American physicians
      received no AMA support in seeking legal remedies to hospital segregation. And
      the NMA and AMA found themselves opposed on other policy issues, including
      Medicaid and Medicare. These differences eventually catalyzed a series of direct
      confrontations. The 1965 AMA meeting in New York City, for example, was protested
      by about 200 NMA-led picketers. The NMA's quest for racial equality in medicine
      was supported by some other medical organizations, such as the Medical Committee
      for Human Rights. In 1966, the AMA House voted to amend the AMA Constitution and
      Bylaws, giving its Judicial Council (now the Council on Ethical and Judicial
      Affairs) the authority to investigate allegations of discrimination. This paved
      the way for a subsequent era of increasing cooperation and understanding.

PMID- 19585921
TI  - Cardiovascular disease in African American women: a health care disparities
      issue.
AB  - OBJECTIVES: To review the current status of cardiovascular disease (CVD) in
      African American women compared to Caucasian women in regards to 4 categories of
      CVD: coronary artery disease (CAD), hypertension, stroke, and congestive heart
      failure (CHF), and to call attention to the need to place more emphasis on the
      need to increase awareness of CVD as the greatest killer of African American
      females in the United States. METHODS: A review of the recent literature on the
      subject of CVD in women over the past several years was conducted with a focus on
      CVD in African American women. Statistical data on incidence, prevalence,
      morbidity and mortality of CAD, hypertension, stroke, and CHF in black and white
      women were compared. RESULTS: Statistical data gathered over the past several
      years indicate that African American women have greater mortality than Caucasian
      women from CAD, hypertension, stroke, and CHF. The mortality rate from CAD is 69%
      higher in black women than in white women. Mortality for black females from
      hypertension is 352% higher than for white females. Age-adjusted stroke death
      rates are 54% higher in African American than in Caucasian women, and the age
      adjusted mortality rate per 100,000 is 113.4 vs. 97.5 for black and white women,
      respectively. Incidence, prevalence, and morbidity figures for CAD, hypertension,
      stroke, and CHF are all higher for African American females than for Caucasian
      females. CONCLUSIONS: African American women are at exceptional risk for CVD, and
      more recognition of this fact as well as greater awareness of the problem should
      be promulgated and distributed by means of public education programs. Physicians
      who treat black patients also need to be encouraged to be more aggressive in
      their efforts to detect patients at risk and to initiate therapy early on in the
      course of CVD in this sub-population.

PMID- 19585920
TI  - Variations in breast cancer screening and health behaviors by age and race among
      attendees of women's health clinics.
AB  - OBJECTIVE: Breast cancer mortality has declined, yet disease outcomes have not
      improved equally across populations. Disparities may initiate early in the
      continuum of care, in health behavior patterns, and screening practices. We
      examined variations in mammography, exercise, fruit and vegetable intake, alcohol
      consumption, and body mass index (BMI, kg/m2) by age and race in a diverse sample
      of clinic patients. METHODS: We analyzed survey data collected at baseline from
      855 women (>40 years old) in women's health clinics, who were recruited for a
      risk-tailored intervention. Screening practices, health behaviors, and
      demographics were surveyed. Statistical analyses were performed using bivariate
      difference tests and multiple logistic regression. RESULTS: Overall, 47% of the
      women were African American, with a mean age of 50 years. Older women were twice
      as likely as younger women to have had mammography within the previous year and
      significantly more likely than women 10 years younger to exercise at least 3
      times weekly. African American women were significantly less likely than white
      women to exercise at least 3 times weekly, eat more than 2 servings daily of
      fruit and vegetables, or report a BMI of less than <25 kg/m2. Mammography rates
      were comparable by race except among lesser-educated African American women, who
      showed higher rates versus comparable white women. CONCLUSIONS: New intervention
      models that link health behavior information with screening messages in clinical
      settings may be important in reducing breast cancer risk and mortality.

PMID- 19585922
TI  - Factors associated with cervical cancer screening compliance and noncompliance
      among Chinese, Korean, Vietnamese, and Cambodian women.
AB  - OBJECTIVE: The purpose of this study was to determine factors associated with
      cervical cancer screening compliance and noncompliance among Chinese, Korean,
      Vietnamese, and Cambodian women aged 18 years and older. METHODS: A cross
      sectional design was used. The sample consisted of 1049 women aged 18 or older,
      of whom 37.94% reported never having been screened for cervical cancer, 23.55%
      reported noncompliance, and 38.51% were in compliance with screening guidelines.
      The sample was comprised of Chinese, 50.58%; Koreans, 17.50%; Vietnamese, 16.15%;
      and Cambodians, 15.77%. RESULTS: Education was significantly associated with
      never having been screened for cervical cancer for Cambodians. Low income
      (<$10000) was significantly associated with never having been screened for
      Cambodian and Chinese women. Not having health insurance was significantly
      correlated with not getting screened for all ethnic groups. Age and living in the
      United States less than 15 years were significantly correlated with never having
      been screened for Vietnamese, Korean, and Chinese women. Marital status was
      significantly correlated with not getting screened for Korean and Chinese women.
      English fluency was significantly associated with screening for Cambodians,
      Koreans, and Chinese. Barriers associated with women who were never screened
      compared to those barriers for women who were screened and were compliant
      included lack of knowledge, psychosocial, no insurance, language, transportation,
      and lack of time, but these barriers were different among the 4 ethnic groups.
      CONCLUSION: Compliance with cervical cancer screening guidelines among Asian
      American women can be enhanced significantly by providing culturally and
      linguistically appropriate educational and early intervention programs.

PMID- 19585924
TI  - Racial disparity in the clinical determinants and outcomes of cesarean
      hysterectomy.
AB  - This study was undertaken to compare the risk factors, indications for and
      complications rates of cesarean hysterectomy in patient from two different ethnic
      backgrounds-whites and nonwhites-using patients who had cesarean hysterectomy in
      the Detroit Medical Center from 1991-2007. During the study period, there were
      42599 cesarean deliveries, making the incidence of cesarean hysterectomy to be
      3.7 per 1000 cesarean deliveries. Of the 158 cases, 8.9% were planned, while
      91.1% were emergent. Among the emergent cases, nonwhites were more likely to have
      a higher parity (median [range], 3 [0-13] vs. 2 [0-9]; p = .025), while whites
      were more likely to have a private insurance (64.7% vs. 29.1%; p = .001; OR,
      4.47; 95% CI, 1.98-10.09]. There were no significant differences in the
      indications for cesarean hysterectomy among the racial groups. Whites were more
      likely to have composite cardiopulmonary complications and urological injury
      compared to nonwhites, (17.6% vs. 3.6%; P = .012; OR, 5.68; 95% CI, 1.50-21.51)
      and (26.5% vs. 10.9%; P = .05; OR 2.94; CI, 1.12-7.75), respectively. In
      conclusion, beyond higher rates of cardiopulmonary complications and urological
      injury among whites, no significant racial differences exist in the risk factors,
      indications for, and complications from cesarean hysterectomy.

PMID- 19585923
TI  - A pilot trial of spirituality counseling for weight loss maintenance in African
      American breast cancer survivors.
AB  - A continuing challenge in weight loss treatment is attaining maintenance of
      weight loss. The goal of this study was to develop a counseling method that would
      assist African American breast cancer survivors with weight loss maintenance. In
      this pilot study, 31 obese breast cancer survivors were recruited.
      Individualized, dietitian-led counseling by telephone and free Weight Watchers
      coupons were provided to all participants for 18 months. At the 6-month time
      point, women were randomized to receive spirituality counseling or not in
      addition to the standard program. The spirituality counseling was delivered via
      telephone using an 8-step framework. Subjects were asked to utilize daily
      meditation or prayer, daily readings, and the recording of thoughts in a journal.
      Mean weight loss from baseline to 6 months was a modest 2.0% of baseline weight.
      From 6 to 18 months, there was no further weight change in the spirituality arm
      and a gain of 0.7% in the dietitian-only arm. Despite little effect on weight
      loss, it did appear that spirituality counseling positively affected spiritual
      well-being (FACIT-Sp) scores and dietary quality. The spirituality counseling
      framework therefore may be further refined and useful for other health promotion
      studies with African American populations.

PMID- 19585925
TI  - Perinatal outcomes in nutritionally monitored obese pregnant women: a randomized
      clinical trial.
AB  - BACKGROUND: Although obesity in pregnancy continues to be associated with ongoing
      health problems, many clinicians have been reluctant to place nondiabetic, obese,
      pregnant women on a monitored, calorie-appropriate nutritional regimen for fear
      of fetal growth restriction, low birth weight, or starvation ketosis. METHODS: A
      total of 257 patients were enrolled in the randomized study, with a loss-to
      follow-up rate of 9.73%. Patients were assigned randomly to either the control
      (unmonitored) group (n=116), consisting of conventional prenatal dietary
      management, or to the study (monitored) group (n=116), which was prescribed a
      balanced nutritional regimen and were asked to record in a diary all of the foods
      eaten during each day. Women were eligible for the study if they were pregnant
      with a single fetus between 12 and 28 weeks of gestation and had a prepregnancy
      body mass index of more than 30 kg/m2. The primary outcome was to compare
      perinatal outcomes in the control vs the study groups. The secondary measure was
      to compare outcomes in adherent and nonadherent patients in the study group.
      RESULTS: Omnibus MANOVA showed statistically significant differences between the
      study and control groups regarding 3 variables: (1) gestational hypertension, p <
      .46; (2) mother's last weight before delivery, p < .001; and (3) mother's 6-week
      postpartum weight, p < .001. Patients gaining 15 pounds or more during their
      pregnancy showed statistically significant differences between the groups for 8
      variables. CONCLUSION: Obese pregnant women may be placed on a healthy, well
      balanced, monitored nutritional program during their antepartum course without
      adverse perinatal outcomes.

PMID- 19585926
TI  - Fetal outcome following cesarean section in a university teaching hospital.
AB  - OBJECTIVE: To evaluate fetal outcome for the various indications for cesarean
      section. METHODOLOGY: A review of all cases of cesarean section that were done in
      the maternity unit at Usmanu Danfodiyo University Teaching Hospital, Sokoto,
      Nigeria, between January 2006 and April 2007, with emphasis on indications and
      perinatal outcome. RESULTS: There were 2562 total deliveries within the study
      period and 112 perinatal deaths giving a perinatal mortality rate of 43.7 per
      1000 live births. Cesarean section accounted for 216 of the deliveries (8.4%)
      with 24 perinatal deaths (11.1%). Perinatal mortality from Cesarean sections
      accounted for 21.4% of the total deaths with severe birth asphyxia responsible
      for most perinatal deaths, 17 of 24 (70.8%). There were 174 emergency sections
      with 22 perinatal deaths, while 42 elective sections had 2 perinatal deaths. The
      main indications for cesarean section were cephalopelvic disproportion, 86
      (39.8%); previous section plus an obstetric abnormality, 39 (18.1%); and
      prolonged obstructed labor, (10.2%), with perinatal deaths of 3, 2 and 1,
      respectively. CONCLUSIONS: The perinatal mortality among the cesarean deliveries
      were 11.1%, and the main cause of death was severe birth asphyxia. Emergency
      cesarean section was more likely than elective to result in a perinatal loss. The
      indication with the poorest fetal outcome was prolonged obstructed labor.

PMID- 19585927
TI  - Maternal prepregnancy underweight and risk of early and late stillbirth in black
      and white gravidas.
AB  - OBJECTIVE: The association between underweight and stillbirth remains poorly
      defined, especially across racial/ethnic sub-populations. We investigate the
      association of pre-pregnancy underweight on the risk for early and late
      stillbirth among black and white mothers. METHODS: We conducted analysis on the
      Missouri maternally linked data files covering the period 1989-1997 inclusive.
      Using body mass index (BMI), we categorized mothers as underweight (BMI <18.5)
      and normal weight (BMI = 18.5-24.9). By applying logistic regression modeling
      with adjustment for intracluster correlation, we estimated the risk for total,
      early (-28 weeks of gestation), and late stillbirth (>28 weeks of gestation)
      among black and white mothers. RESULTS: A total of 1808 cases of stillbirth were
      registered. The rate of stillbirth among white mothers was 3.7 per 1000, while
      the rate among blacks was 7.1 per 1000. Underweight black mothers had comparable
      risk for total (OR, 0.9; 95% CI, 0.7-1.2), early (OR, 1.1; 95% CI, 0.8-1.5), and
      late stillbirth (OR, 0.8; 95% CI, 0.5-1.2) as compared to their normal-weight
      counterparts. By contrast, underweight white gravidas had a 30% reduced
      likelihood (OR, 0.7; 95% CI, 0.6-0.9) for late stillbirth as compared to normal
      weight white mothers. However, the risks for total and early stillbirth among
      underweight white mothers were similar to those of normal-weight white mothers.
      CONCLUSION: Low prepregnancy BMI has similar effects on fetal survival in both
      blacks and whites except for late stillbirth. The underweight white survival
      advantage over blacks in late pregnancy could probably be due to greater access
      for identified white at-risk groups to effective obstetrical interventions as
      previously reported.

PMID- 19585928
TI  - Calcium supplement use by African American women.
AB  - INTRODUCTION: Inadequate calcium intake is more common among women belonging to
      racial and ethnic minorities. This study examined the patterns and
      characteristics associated with calcium supplement use or nonuse among African
      American women, and the potential impact of physician recommendation on calcium
      supplementation. METHODS: African American women aged 19 to 65, attending
      community outreach activities sponsored by a multispecialty academic medical
      center in northeastern Ohio, completed a calcium supplement survey. Survey items
      included demographic and bone health-related information, and rationale for
      calcium supplement use or nonuse. RESULTS: Of 160 respondents, 14% of women
      regularly took calcium supplements, 16% were former users, and 70% never used
      calcium supplements. Characteristics associated with calcium use status included
      age, multivitamin use, and marital status. Few African American women recall
      discussions with their doctors about calcium intake. Most who formerly took
      calcium supplements and most who had never taken them were willing to do so if
      recommended by their physician. DISCUSSION: Calcium supplement use among African
      American women in this study was low. However, many of the barriers to calcium
      supplement use by African American women appear remediable through brief calcium
      intake counseling by their physician.

PMID- 19585929
TI  - A review of clinical pattern and outcome of vesicovaginal fistula.
AB  - OBJECTIVES: The aim of this study was to determine the incidence,
      sociodemographic parameters, and outcome of surgical repairs of obstetric fistula
      in our center. METHODS: Case files of patients managed for genital tract fistula
      over a 10-year period (January 1, 1997 to December 31, 2006) were retrieved and
      analyzed. RESULTS: Fifty-five patients with of genital tract fistula were managed
      in the period under review, constituting 1.17% of total gynecological admissions.
      Obstetric fistula accounted for 51 (93%) of genital fistula, and 92.7% of cases
      were caused by prolonged obstructed labor. The most common form of fistula was
      the midvaginal type, and 89% of affected women were married with primiparous
      women mostly affected (43.6%). Menstrual function was lost in 51% of the
      patients, while obstetric palsy complicated 18.2% of the cases. Half of the women
      (51%) were abandoned by their spouses, and surgical repair was successful in only
      32% of the cases. CONCLUSION: Obstetric fistula continues to show the deficiency
      in women's general health status occasioned by poor childbirth attendance in
      developing countries. Affected women suffer double jeopardy as a result of dearth
      of appropriate experts in fistula repair.

PMID- 19585930
TI  - The tragedy of childbirth vesicovaginal fistula: time for action.

PMID- 19585931
TI  - Barriers to blood pressure control as reported by African American patients.
AB  - PURPOSE: To understand African American patients' opinions as to barriers to
      hypertension treatment. METHODS: Focus groups (n=3) were led by a trained African
      American moderator of African American patients with hypertension (n=26) who
      receive their care from a large primary care network. Discussions were
      transcribed verbatim. Information was displayed in a data matrix and analyzed for
      emerging themes. Descriptive statistics were used to enhance the content validity
      of lifestyle modification efforts planned as part of this ongoing research.
      RESULTS: Most participants were female (n=20), and the mean age was 49 years. All
      participants were at least high school graduates. Four major levels of influence
      emerged from data analysis: (1) the health care system, (2) the community, (3)
      the family, and (4) the individual. The most prevalent concerns about
      hypertension centered on sodium, diet, neighborhoods, mistrust, and denial. Of
      great concern was lack of provider trust and a fatalistic, hopeless mindset. To
      improve trust, our participants suggested developing a hypertension education
      program and providing patients with culturally specific materials. CONCLUSIONS:
      Culturally sensitive materials need to be designed and tested to improve blood
      pressure control. Community input regarding cultural issues is essential for
      designing effective and successful programs for reducing health disparities.

PMID- 19585932
TI  - Treatment options for hepatitis C and the rationale for low response rates in
      African Americans.
AB  - Hepatitis C virus (HCV), the leading cause for liver transplantation, is emerging
      as1 of the infections that pose public health problems in the world since about
      170 million people worldwide are infected with this virus. Inequality in
      addressing racial/ethnic disparities in treatment for hepatitis C is a pressing
      problem. HCV is more common among African Americans than among other racial
      groups in the United States. Although African Americans have been shown to have a
      lower rate of viral clearance and a higher rate of chronic hepatitis C, they may
      have at the same time a much lower rate of fibrosis progression compared to
      Caucasians. The purpose of this study is to summarize treatment options available
      for hepatitis C in African Americans and to describe the different mechanisms
      thought to be the reasons for the disparate response to treatment in African
      Americans.

PMID- 19585933
TI  - Women's sexual health; empowering African American women and teenage girls with
      the facts.

PMID- 19585934
TI  - Uterine leiomyoma in an adolescent female.
AB  - BACKGROUND: Uterine myomas are the most frequently occurring neoplasms in the
      female pelvis, presenting in approximately one-third of women. Fewer than half
      develop menstrual abnormalities, pelvic pain, and discomfort. Large myomas may
      compromise fertility. These tumors very rarely occur in the pediatric and
      adolescent population. When suspected on examination, careful evaluation is
      necessary to distinguish the tumor from an adnexal lesion. CASE: A 17-year-old
      girl presented with a large asymptomatic pelvic mass, which was clinically
      suspected to be a leiomyoma. An initial sonographic study was questionable for a
      myoma but was confirmed on subsequent magnetic resonance imaging (MRI). A large
      myoma was noted and removed at surgery. The patient subsequently became pregnant
      and delivered at term by caesarean section. SUMMARY AND CONCLUSION: Leiomyomas of
      the uterus in women under 20 years of age are rare and occur much less often than
      adnexal lesions. Although ultrasound studies are usually sufficient to make the
      distinction between the 2, MRI generally is superior to sonography in this
      regard. In this young population, myomectomy is the surgical procedure of choice
      to preserve fertility.

PMID- 19585935
TI  - Manifestations of cutaneous sarcoidosis: a case report of an African American
      woman.
AB  - Cutaneous sarcoidosis is challenging to diagnose due to its many nonspecific
      manifestations. In this report we describe a case of cutaneous sarcoidosis in a
      patient presenting with multiple lesions. Diagnosis of the disease involves not
      only clinical and pathologic findings but also multiple exclusions.

PMID- 19585937
TI  - A shared commitment to ending disparities in care.

PMID- 19585936
TI  - The presidents Drs. Carolyn Britton, MD, MS, of the NMA and Nancy Nielsen, MD,
      PhD, of the AMA: an interview by George Dawson.
AB  - In this edition, we are privileged to have interviewed the current presidents of
      the National Medical Association (NMA), founded in 1895, and the American Medical
      Association (AMA), founded in 1847. Drs. Carolyn Britton of the NMA and Nancy
      Nielsen of the AMA are the 109th and 163rd presidents of their respective
      organizations. As part of the reconciliation efforts begun by the issuance of a
      formal apology by the AMA to the nations' African American physicians and the
      NMA, as they relate to our collective American racial history, we felt it
      important to include in this process the views of both organizations' presidents.
      And it just so happens that in this time both presidents happen to be women. The
      NMA elected its first female president (Edith Erby-Jones, MD) in 1985 and, as of
      today, they have selected 9 female presidents. The AMA selected its first female
      president (Nancy Dickey, MD) in 1998, with Dr. Nielsen serving as the second
      female president ever in AMA history.

PMID- 19585938
TI  - Liability and disaster relief.

PMID- 19585939
TI  - Red Flags Rule: the Fair and Accurate Credit Transaction Act.

PMID- 19585940
TI  - KMA flexes defensive muscle in '09 session: achieves priority of an increased
      cigarette tax.

PMID- 19585941
TI  - Is enhanced energy utilization the answer to prevention of excessive adiposity?
AB  - Excessive adiposity is the result of an imbalance in energy homeostasis whereby
      excessive food intake is not balanced by increased energy utilization. Much has
      been learned about the physiology of energy expenditure during resting, eating,
      and physical activity that allows optimal energy utilization that could reduce
      excessive adiposity. Resting metabolic rate and diet-induced thermogenesis
      collectively contribute 75% of energy expenditure that is largely based on
      carbohydrate rather than fat metabolism. Conversely, physical activity, whether
      active (planned) or spontaneous (non-exercise activity thermogenesis),
      predominately utilizes fatty acids as sources of energy expenditure. Such
      enhanced fat-derived thermogenesis most optimally results in weight loss to
      achieve maintenance of balanced energy homeostasis. While decreased energy
      expenditure of 100-200 Kcal/day from sedentary activities can cause weight gain,
      unplanned spontaneous physical activity expenditure of 100-800 Kcal/day from
      routine activities such as walking and fidgeting is sufficient to prevent weight
      gain. Furthermore, planned physical activity can be enhanced up to 16-fold, such
      that additional fat thermogenesis can be optimized. Such physical activity also
      achieves adaptive conditioning for more efficient energy utilization and weight
      loss. It is, therefore, necessary that children as well as adults embrace all
      forms of non-exercise and planned active exercise activities to achieve optimal
      fat thermogenesis for optimal energy homeostasis including weight loss for either
      the overweight or obese. Such lifestyles need to be promoted through educational,
      environmental, and legislative changes that optimize healthy nutrition and
      physical activity.

PMID- 19585943
TI  - Prescription roulette.

PMID- 19585942
TI  - Novel animal model for teaching chest tube placement.
AB  - BACKGROUND: The number of procedures available to pediatric residency trainees is
      few in number and patient size leaves little margin for error. Artificial
      simulation labs have not been developed for neonatal chest tubes. Use of live
      animal models is coming under increased scrutiny and is expensive. METHODS: We
      conducted a simulation skills lab for neonatal chest tube placement using a fryer
      chicken model. Thirty incoming pediatric interns were prospectively queried on
      comfort levels of inserting chest tubes prior to and following the simulation
      lab. RESULTS: On a 5-point Likert scale, comfort levels increased from a median
      of 1 to 3. All interns reported feeling more comfortable with chest tube
      placement and all reported having better understanding of the process of chest
      tube placement following the procedure lab. CONCLUSION: The fryer chicken model
      is an advantageous, effective model of teaching chest tube placement.

PMID- 19585944
TI  - School related athletic activities.

PMID- 19585945
TI  - Elderly people posing a number of problems.

PMID- 19585946
TI  - Alzheimer's disease and mild cognitive impairment.

PMID- 19585948
TI  - Novel strategies for the prevention of dementia from Alzheimer's disease.
AB  - As the world's population continues to age, Alzheimer's disease presents a
      looming public health crisis that, left unchecked, threatens to overwhelm health
      care systems throughout the developed world. In order to significantly tackle the
      most catastrophic and devastating symptom of Alzheimer's disease (AD)--dementia-
      we must be able to detect the disease prior to the onset of clinical symptoms,
      and be able to offer patients preventative treatments that block or significantly
      slow disease progression. This review summarizes a variety of the most promising
      early detection methods for Alzheimer's disease (AD) and mild cognitive
      impairment (MCI) that could be used to identify those at high risk of developing
      the disease and used for monitoring disease progression and response to
      investigational treatments. In addition, treatment research programs that could
      be developed into disease-modifying treatments that significantly delay the
      development of dementia are highlighted. These potential treatments target many
      different pathways, and may one day be dosed in combination to increase efficacy
      and prevent cognitive deterioration in patients with AD. While we still face
      numerous challenges, AD researchers have made great progress in understanding
      disease mechanisms. As we have seen in the treatment of heart disease, even
      modest preventative treatments can have hugely significant clinical outcomes and
      drastically reduce disease prevalence on a population scale. Therefore, there is
      hope that the development of prophylactic treatments, combined with improved
      early detection methods, will provide dramatic relief for millions of aging
      individuals threatened by the specter of Alzheimer's disease.

PMID- 19585949
TI  - Early detection of Alzheimer's disease: new diagnostic criteria.
AB  - There has been unprecedented growth of scientific knowledge about Alzheimer's
      disease (AD). The description of distinctive and reliable biomarkers that are now
      available through structural brain imaging with magnetic resonance imaging,
      molecular neuroimaging with positron emission tomography, and cerebrospinal fluid
      analyses, and a better definition of the clinical profile of amnestic disorders
      that occur early in the course of the disease, make it possible to identify AD
      with high accuracy, even in the early stages of the disease. Accordingly, new
      criteria for the diagnosis have been proposed that capture both the prodromal and
      the more advanced dementia stages of the disease in the same diagnostic
      framework.

PMID- 19585947
TI  - Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies
      toward intervention.
AB  - More than 25 million people in the world today are affected by dementia, most
      suffering from Alzheimer's disease. In both developed and developing nations,
      Alzheimer's disease has had tremendous impact on the affected individuals,
      caregivers, and society. The etiological factors, other than older age and
      genetic susceptibility, remain to be determined. Nevertheless, increasing
      evidence strongly points to the potential risk roles of vascular risk factors and
      disorders (eg, cigarette smoking, midlife high blood pressure and obesity,
      diabetes, and cerebrovascular lesions) and the possible beneficial roles of
      psychosocial factors (eg, high education, active social engagement, physical
      exercise, and mentally stimulating activity) in the pathogenetic process and
      clinical manifestation of the dementing disorders. The long-term multidomain
      interventions toward the optimal control of multiple vascular risk factors and
      the maintenance of socially integrated lifestyles and mentally stimulating
      activities are expected to reduce the risk or postpone the clinical onset of
      dementia, including Alzheimer's disease.

PMID- 19585950
TI  - Biological markers for early detection and pharmacological treatment of
      Alzheimer's disease.
AB  - The introduction of biological markers in the clinical management of Alzheimer's
      disease (AD) will not only improve diagnosis relating to early detection of
      neuropathology with underlying molecular mechanisms, but also provides tools for
      the assessment of objective treatment benefits. In this review, we identify a
      number of in vivo neurochemistry and neuroimaging techniques, which can reliably
      assess aspects of physiology, pathology, chemistry, and neuroanatomy of AD, and
      hold promise as meaningful biomarkers in the early diagnostic process, as well as
      for the tracking of disease-modifying pharmacological effects. These
      neurobiological measures appear to relate closely to pathophysiological,
      neuropathological, and clinical data, such as hyperphosphorylation of tau, abeta
      metabolism, lipid peroxidation, pattern and rate of atrophy, loss of neuronal
      integrity, and functional and cognitive decline, as well as risk of future
      decline. As a perspective, the important role of biomarkers in the development of
      innovative drug treatments for AD and the related regulatory process is
      discussed.

PMID- 19585951
TI  - Mechanism-based treatments for Alzheimer's disease.
AB  - Treatment for Alzheimer's disease is entering a new and exciting phase, with
      several new drugs beginning clinical trials. Many of these new therapies are
      based on our best current understanding of the pathogenesis of Alzheimer's
      disease, and are designed to try to either slow or halt the progression of the
      disease. There are several different theories underlying the current efforts, and
      these are briefly reviewed. Therapies directed against some aspect of beta
      amyloid formation, against neurofibrillary tangle formation and against the
      inflammatory response are all considered, as are the problems associated with
      each area. It is as yet unclear which, if any, of these approaches will be
      successful, but the high level of activity in each of these three fields provides
      some hope that an effective treatment for Alzheimer's disease is on the horizon.

PMID- 19585952
TI  - Is there a neuropathology difference between mild cognitive impairment and
      dementia?
AB  - The number of studies that have investigated the neuropathology of mild cognitive
      impairment (MCI) is small, but growing. In this paper we have restricted our
      focus to the consideration of the presence and extent of postmortem findings
      relevant to the neuropathology of Alzheimer's disease. We have drawn from studies
      that have investigated the postmortem neurobiology of the brains of persons with
      cognitive function at the interface between unimpaired normal function and mild
      but definite dementia. The data derived from these studies suggest that i) the
      brains of persons with MCI evidence significant neuropathological and
      neurobiological changes relative to those without cognitive impairment; ii) in
      general, the neuropathological and neurobiological changes are qualitatively
      similar to those observed in the brains of persons with frank AD-like dementia;
      and iii) the neuropathological and neurobiological brain changes associated with
      MCI are quantitatively less than those of persons who meet criteria for dementia.
      Thus, the available, albeit limited, data suggests that MCI is associated with
      the early stages of the neurobiological and neuropathological changes that
      culminate in the florid lesions of AD; including the accumulation of neuritic
      plaques, neurofibrillary tangles, synaptic and neurotransmitter associated
      deficits, and significant neuronal cell death.

PMID- 19585954
TI  - Imaging in Alzheimer's disease.
AB  - Neuroimaging in the early differential diagnosis of dementia has gained
      considerable interest over the last decade. From being used for exclusive
      purposes only, neuroimaging is now in the forefront of aiding in the diagnosis of
      Alzheimer's disease (AD), frontotemporal dementia, vascular dementia, and and
      dementia with Lewy bodies (DLB). With the exception of dopamine transporter
      single photon-emission computed tomography imaging in DLB, imaging has not yet
      been incorporated into the diagnostic criteria for the various dementia
      syndromes, but that will soon change. The recently formulated research criteria
      for early AD recently formulated by Dubois et al explicitly mention magnetic
      resonance imaging and positron emission tomography for AD, and are an example of
      a new diagnostic process developing. In this review, the various imaging
      techniques will be highlighted, with an emphasis on their ability to diagnose
      Alzheimer's disease and separate it from other entities.

PMID- 19585953
TI  - Structural neuroimaging in Altheimer's disease: do white matter hyperintensities
      matter?
AB  - The targeted brain dysfunction that accompanies aging can have a devastating
      effect on cognitive and intellectual abilities. A significant proportion of older
      adults experience precipitous cognitive decline that negatively impacts
      functional activities. Such individuals meet clinical diagnostic criteria for
      dementia, which is commonly attributed to Alzheimer's disease (AD). Structural
      neuroimaging, including magnetic resonance imaging (MRI), has contributed
      significantly to our understanding of the morphological and pathology-related
      changes that may underlie normal and disease-associated cognitive change in
      aging. White matter hyperintensities (WMH), which are distributed patches of
      increased hyperintense signal on T2-weighted MRI, are among the most common
      structural neuroimaging findings in older adults. In recent years, WMH have
      emerged as robust radiological correlates of cognitive decline. Studies suggest
      that WMH distributed in anterior brain regions are related to decline in
      executive abilities that is typical of normal aging, whereas WMH distributed in
      more posterior brain regions are common in AD. Although epidemiological,
      observational, and pathological studies suggest that WMH may be ischemic in
      origin and caused by consistent or variable hypoperfusion, there is emerging
      evidence that they may also reflect vascular deposition of beta-amyloid,
      particularly when they are distributed in posterior areas and are present in
      patients with AD. Findings from the literature highlight the potential
      contribution of small-vessel cerebrovascular disease to the pathogenesis of AD,
      and suggest a mechanistic interaction, but future longitudinal studies using
      multiple imaging modalities are required to fully understand the complex role of
      WMH in AD.

PMID- 19585956
TI  - Is dementia preventable?
AB  - Dementia is an important public health problem of increasing magnitude. At
      present, available therapies provide only minor and temporary relief, and
      attempts to find a cure have so far failed. Epidemiological studies have
      identified risk factors for dementia, particularly Alzheimer's disease and
      vascular dementia. In principle, these findings provide an opportunity to
      intervene and prevent the dementia epidemic. Attention to nongenetic risk factors
      such as hypertension, hyperlipidemia, smoking, and obesity may thus not only
      prevent cardiovascular disease but also dementia, although it is difficult to
      prove the efficacy of these measures for dementia prevention.

PMID- 19585955
TI  - The effects of cardiovascular risk factors on cognitive compromise.
AB  - As life expectancy in the United States continues to increase, the projected
      numbers of elderly people who will develop dementia will grow rapidly. This paper
      reviews four well-established cardiovascular risk factors (type 2 diabetes,
      hypertension, cholesterol, and inflammation), for which there is longitudinal
      epidemiological evidence of increased risk of dementia, Alzheimer's disease, mild
      cognitive impairment, and cognitive decline. These risk factors are of special
      interest because of their potential modifiability, which may affect the course of
      cognitive compromise. Diabetes is the cardiovascular risk factor (CvRF) most
      consistently associated with cognition. Hypertension in midlife is consistently
      associated with cognition, but its associations with late-life hypertension are
      less clear. Total cholesterol is not consistently associated with cognition.
      Interleukin-6 and C-reactive protein are inflammatory markers relatively
      consistently associated with cognition. Composites of the CvRFs increase the risk
      for dementia in a dose-dependent fashion, suggesting a cumulative effect of these
      factors on neuronal stress. In the relatively few studies that have reported
      interactions of risk factors, they potentiate each other. The effect of each of
      these risk factors varies according to apolipoprotein E genotype. It may be that
      the effect of these risk factors varies according to the presence of the others,
      and these complex relationships underlie the biological mechanisms of cognitive
      compromise. This may be crucial for understanding the effects on cognition of
      drugs and other approaches, such as lifestyle change, for treating these risk
      factors.

PMID- 19585958
TI  - New life for frequency lowering?

PMID- 19585957
TI  - Family caregivers of people with dementia.
AB  - Family caregivers of people with dementia, often called the invisible second
      patients, are critical to the quality of life of the care recipients. The effects
      of being a family caregiver, though sometimes positive, are generally negative,
      with high rates of burden and psychological morbidity as well as social
      isolation, physical ill-health, and financial hardship. Caregivers vulnerable to
      adverse effects can be identified, as can factors which ameliorate or exacerbate
      burden and strain. Psychosocial interventions have been demonstrated to reduce
      caregiver burden and depression and delay nursing home admission. Comprehensive
      management of the patient with dementia includes building a partnership between
      health professionals and family caregivers, referral to Alzheimer's Associations,
      and psychosocial interventions where indicated.

PMID- 19585959
TI  - Effect of linear frequency transposition on speech recognition and production of
      school-age children.
AB  - PURPOSE: To investigate the clinical efficacy of linear frequency transposition
      (LFT) for a group of school-age children. RESEARCH DESIGN: A nonrandomized,
      within-subject design was implemented to investigate vowel and consonant
      recognition and fricative articulation of school-age children utilizing this
      feature. STUDY SAMPLE: Ten children, aged 6 years and 3 months, to 13 years and 6
      months from a special education school district participated in this study.
      Individual hearing thresholds ranged from normal to moderate in the low
      frequencies and from severe to profound in the high frequencies. Average language
      age of children was within 2.2 years of chronological age. DATA COLLECTION AND
      ANALYSIS: Phoneme recognition and fricative articulation performance were
      compared for three conditions: (1) with the children's own hearing aids, (2) with
      an advanced hearing instrument utilizing LFT, and (3) with the same instrument
      without LFT. Nonsense syllable materials were administered at 30 and 50 dB HL
      input levels. Fricative articulation was measured by analyzing speech samples of
      conversational speech and oral reading passages. Repeated measures general linear
      model was utilized to determine the significance of any noted effects. RESULTS:
      Results indicated significant improvements in vowel and consonant recognition
      with LFT for the 30 dB HL input level. Significant improvement in the accuracy of
      production of high-frequency (HF) fricatives after six weeks of use of LFT was
      also observed. CONCLUSIONS: These results suggest that LFT is a potentially
      useful hearing aid feature for school-age children with a precipitous HF
      sensorineural hearing loss.

PMID- 19585960
TI  - Technical report: distortion product otoacoustic emissions that are not outer
      hair cell emissions.
AB  - PURPOSE: To present a case study in order to alert clinicians to the possibility
      of occurrence of intermodulation distortion during otoacoustic emissions testing
      that arises from the cavity formed by the external auditory meatus and tympanic
      membrane rather than from the inner ear, compromising the reliability and
      validity of otoacoustic emissions testing. RESEARCH DESIGN: Prospective case
      study. STUDY SAMPLE: A young (26-year-old) female adult with a longstanding,
      bilateral, essentially moderate to severe sensorineural hearing loss presented
      with robust distortion product otoacoustic emissions. RESULTS: Repeat otoacoustic
      emissions testing with another device of the same model revealed essentially
      absent distortion product otoacoustic emissions and transient otoacoustic
      emissions. Calibration of both otoacoustic emissions devices using a 1 cc
      membranous cavity indicated present intermodulation distortion for the device
      that yielded robust distortion product otoacoustic emissions for the patient but
      absent intermodulation distortion for the device that revealed absent distortion
      product otoacoustic emissions and absent transient evoked otoacoustic emissions
      for the patient. The calibration findings for the device yielding intermodulation
      distortion in the cavity were confirmed by an engineer of a technical
      instrumentation company. The device was shipped back to the manufacturer of the
      device for repair. The manufacturer's engineers diagnosed the problem as an
      interruption in the relay system. Following repair, calibration revealed the
      absence of intermodulation distortion in the 1 cc membranous cavity. CONCLUSIONS:
      The findings have implications for the reliability and validity of otoacoustic
      emissions. Clinicians should routinely calibrate otoacoustic emissions devices
      using 1.0 and 0.5 cc membranous cavities to rule out intermodulation distortion
      that could produce artifactual otoacoustic emissions in patients.

PMID- 19585961
TI  - Fukuda stepping test: sensitivity and specificity.
AB  - BACKGROUND: A vestibulospinal test known as the Fukuda stepping test (FST) has
      been suggested to be a measure of asymmetrical labyrinthine function. However, an
      extensive review of the performance of this test to identify a peripheral
      vestibular lesion has not been reported. PURPOSE: The purpose of this study was
      to evaluate the sensitivity and specificity of the standard FST and a head
      shaking variation for identification of a peripheral vestibular system lesion.
      RESEARCH DESIGN: In this retrospective review, we compared performance on the FST
      with and without a head shaking component to electronystagmography (ENG) caloric
      irrigation unilateral weakness results. STUDY SAMPLE: We studied these factors in
      736 chronic dizzy patients. RESULTS: Receiving operating characteristics (ROC)
      analysis and area under the curve (AUC) indicated no significant benefit to
      performance from the head shaking variation compared to the standard FST in
      identifying labyrinthine weakness as classified by caloric unilateral weakness
      results. CONCLUSIONS: These findings suggest that the FST with and without head
      shake component is not a reliable screening tool for peripheral vestibular
      asymmetry in chronic dizzy patients; however, future research may hold promise
      for the FST as a tool for patients with acute unilateral disorders.

PMID- 19585962
TI  - Tinnitus distress, anxiety, depression, and hearing problems among cochlear
      implant patients with tinnitus.
AB  - BACKGROUND: While several studies have investigated the presence and annoyance of
      tinnitus in cochlear implant (CI) recipients, few studies have probed the
      handicap experienced in association with tinnitus in this population. PURPOSE:
      The aim of this study was to use validated self-report measures in a consecutive
      sample of CI patients who reported tinnitus in order to determine the extent of
      tinnitus handicap. RESEARCH DESIGN: In a retrospective design, a total of 151
      patients (80% response rate) responded to a postal questionnaire, and of these,
      111 (74%) reported that they currently experienced tinnitus and were asked to
      complete the full questionnaire. Sampling was performed at a point of a mean 2.9
      years postsurgery (SD = 1.8 years). Three established self-report questionnaires
      were included measuring tinnitus handicap (Tinnitus Handicap Inventory [THI]),
      hearing problems (Gothenburg Profile), and finally, a measure of anxiety and
      depression (Hospital Anxiety and Depression Scale). We analyzed the data by means
      of Pearson product moment correlations, t-tests, ANOVAs, and chi-square. RESULTS:
      Data from the validated questionnaires showed relatively low levels of tinnitus
      distress, moderate levels of hearing problems, and low scores on the anxiety and
      depression scales. Using the criteria proposed for the THI (which was completed
      by 107 patients), 35% (N = 38) had a score indicating "no handicap," 30% (N = 32)
      "mild handicap" 18% (N = 19) "moderate handicap", and 17% (N = 18) "severe
      handicap." Thus 37 individuals from the total series of 151 reported moderate to
      severe tinnitus handicap (24.5%). Tinnitus distress was associated with increased
      hearing problems, anxiety, and depression. CONCLUSION: Tinnitus can be a
      significant problem following CI, but that the experienced distress is often
      moderate. However, a quarter of CI recipients do demonstrate moderate/severe
      tinnitus handicap, and thus are candidates for tinnitus specific therapy. The
      level of tinnitus handicap is associated with hearing problems and psychological
      distress.

PMID- 19585963
TI  - Expectations, prefitting counseling, and hearing aid outcome.
AB  - BACKGROUND: Data suggest that having high expectations about hearing aids results
      in better overall outcome. However, some have postulated that excessively high
      expectations will result in disappointment and thus poor outcome. It has been
      suggested that counseling patients with unrealistic expectations about hearing
      aids prior to fitting may be beneficial. Data, however, are mixed as to the
      effectiveness of such counseling, in terms of both changes in expectations and
      final outcome. PURPOSE: The primary purpose of this study was to determine
      whether supplementing prefitting counseling with demonstration of real-world
      listening can (1) alter expectations of new hearing aid users and (2) increase
      satisfaction over verbal-only counseling. Secondary goals of the study were to
      examine (1) the relationship between prefitting expectations and postfitting
      outcome, and (2) the effect of hearing aid fine-tuning on hearing aid outcome.
      RESEARCH DESIGN: Sixty new hearing aid users were fitted binaurally with Beltone
      Oria behind-the-ear digital hearing aids. Forty participants received prefitting
      counseling and demonstration of listening situations with the Beltone AVE (Audio
      Verification Environment) system; 20 received prefitting counseling without a
      demonstration of listening situations. Hearing aid expectations were measured at
      initial contact and following prefitting counseling. Reported hearing aid outcome
      was measured after eight to ten weeks of hearing aid use. STUDY SAMPLE: Sixty new
      hearing aid users aged between 55 and 81 years with symmetrical sensorineural
      hearing loss. INTERVENTION: Participants were randomly assigned to one of three
      experimental groups, between which the prefitting counseling and follow-up
      differed: Group 1 received prefitting counseling in combination with
      demonstration of listening situations. Additionally, if the participant had
      complaints about sound quality at the follow-up visit, the hearing aids were fine
      tuned using the Beltone AVE system. Group 2 received prefitting counseling in
      combination with demonstration of listening situations with the Beltone AVE
      system, but no fine-tuning was provided at follow-up. Group 3 received prefitting
      hearing aid counseling that did not include demonstration of listening, and the
      hearing aids were not fine-tuned at the follow-up appointment. RESULTS: The
      results showed that prefitting hearing aid counseling had small but significant
      effects on expectations. The two forms of counseling did not differ in their
      effectiveness at changing expectations; however, anecdotally, we learned from
      many participants that that they enjoyed listening to the auditory demonstrations
      and that they found them to be an interesting listening exercise. The data also
      show that positive expectations result in more positive outcome and that hearing
      aid fine-tuning is beneficial to the user. CONCLUSIONS: We conclude that
      prefitting counseling can be advantageous to hearing aid outcome and recommend
      the addition of prefitting counseling to address expectations associated with
      quality of life and self-image. The data emphasize the need to address
      unrealistic expectations prior to fitting hearing aids cautiously, so as not to
      decrease expectations to the extent of discouraging and demotivating the patient.
      Data also show that positive expectations regarding the impact hearing aids will
      have on psychosocial well-being are important for successful hearing aid outcome.

PMID- 19585964
TI  - Large area fabrication of tuned polystyrene/poly(methylmethacrylate) periodic
      structures using laser interference patterning.
AB  - The fabrication of advanced architectures in poly(methylmethacrylate-co-styrene)
      (PMMA-S) copolymers (ranging from 12 to 66% mol content of methylmethacrylate)
      using direct laser interference patterning is reported. For all copolymer
      compositions, two different regimes were observed. At low laser intensities, the
      irradiated surfaces swell up due to the formation of microbubbles that result
      from the degradation of the methylmetacrylate (MMA) component. While laser
      ablation produces concave holes, the swelling process permits fabrication of
      convex hemispherical dots. At higher intensities the bubbles release from the
      surface forming a periodic micropored structure. In addition, the laser fluence
      necessary to swell the polymeric surface (swelling threshold) does not depend on
      polymer composition, while the ablation threshold, which determines the
      transition to the periodic micropored structure, strongly depends on the MMA
      content. This observation can be explained by the mechanical and chemical
      properties of the copolymer. The method provides a unique way to produce
      periodical structures protruding from the polymer surface.

PMID- 19585965
TI  - Biomimetic total synthesis of (+/-)-8-oxoerymelanthine.
AB  - Erymelanthine 1 and 8-oxoerymelanthine 2 are unique erythrina alkaloids
      containing a pyridine ring. We synthesized (+/-)-8-oxoerymelanthine 2 in 2.0%
      overall yield using the following key reactions. The characteristic 6-5-6-6
      membered ring system was constructed by the stereoselective intermolecular Diels
      Alder reaction. Oxidative cleavage of the aromatic D-ring was conducted chemo-
      and regioselectively by ozonolysis in the presence of BF(3)-etherate. This
      cleavage site is identical to the site cleaved during the biosynthesis of
      erymelanthine 1. Nitrogen incorporation was achieved by aminolysis. Conversion of
      the D-ring pyridone to the corresponding pyridine was efficiently accomplished by
      palladium-catalyzed reduction of aryl triflate 21. This is not only the first
      total synthesis of (+/-)-8-oxoerymelanthine 2 (where the D-ring is pyridine) but
      also, more importantly, a biomimetic total synthesis of an erythrinan D-aza
      alkaloid.

PMID- 19585966
TI  - Rotational contour analysis of jet-cooled methyl hydroperoxide action spectra in
      the region of the 2nu(OH) and 3nu(OH) bands.
AB  - State-selected photodissociation is used to record the partially rotationally
      resolved action spectra of CH(3)OOH in the region of its first and second OH
      stretching overtones (2nu(OH) and 3nu(OH)) under free-jet expansion conditions.
      From an analysis of the rotational band contours for the OH-stretching states and
      their corresponding COOH torsion combination bands, effective rotational
      constants and transition dipole moment orientations are determined for the
      vibrational eigenstates. The level splitting between the lowest symmetric and
      antisymmetric pair of COOH torsion levels, 0(+) and 0(-), associated with the
      2nu(OH) overtone state is found to be approximately 3.9 cm(-1). Comparison of
      spectra in the region of the 2nu(OH) and 2nu(OH) + nu(COOH) bands in CH(3)OOH and
      CD(3)OOH reveals that the spectral features in CH(3)OOH are substantially more
      perturbed compared to those of its deuterated counterpart, suggesting that modes
      involving the methyl rotor contribute significantly to promoting intramolecular
      vibrational energy redistribution (IVR) in CH(3)OOH. Furthermore, a comparison of
      the average rotational line widths in both CH(3)OOH and CD(3)OOH for the 2nu(OH)
      and 2nu(OH) + nu(COOH) bands appears to suggest that at these energies, adding
      one quanta of low-frequency COOH torsional motion does not enhance the IVR rate
      relative to that of the pure OH-stretching overtone.

PMID- 19585967
TI  - Experimental line parameters of the b1 Sigma(g)+ <-- X3 Sigma(g)- band of oxygen
      isotopologues at 760 nm using frequency-stabilized cavity ring-down spectroscopy.
AB  - Positions, intensities, self-broadened widths, and collisional narrowing
      coefficients of the oxygen isotopologues 16O18O, 16O17O, 17O18O, and 18O18O have
      been measured for the b1 Sigma(g) + <-- X3 Sigma(g) - (0,0) band using frequency
      stabilized cavity ring-down spectroscopy. Line positions of 156 P-branch
      transitions were referenced against the hyperfine components of the 39K D1 (4s
      2S1/2 --> 4p 2P1/2) and D2 (4s 2S1/2 --> 4p 2P3/2) transitions, yielding
      precisions of approximately 0.00005 cm-1 and absolute accuracies of 0.00030 cm-1
      or better. New excited b1 Sigma(g) + state molecular constants are reported for
      all four isotopologues. The measured line intensities of the 16O18O isotopologue
      are within 2% of the values currently assumed in molecular databases. However,
      the line intensities of the 16O17O isotopologue show a systematic, J-dependent
      offset between our results and the databases. Self-broadening half-widths for the
      various isotopologues are internally consistent to within 2%. This is the first
      comprehensive study of the line intensities and shapes for the 17O18O or 18O2
      isotopologues of the b1Sigma(g) + <-- X3 Sigma(g) - (0,0) band of O2. The 16O2,
      16O18O, and 16O17O line parameters for the oxygen A-band have been extensively
      revised in the HITRAN 2008 database using results from the present study.

PMID- 19585968
TI  - An unexpected rearrangement that disassembles alkyne moiety through formal
      nitrogen atom insertion between two acetylenic carbons and related cascade
      transformations: new approach to Sampangine derivatives and polycyclic aromatic
      amides.
AB  - This work analyzes multiple new reaction pathways which originate from
      intramolecular reactions of activated alkynes with the appropriately positioned
      multifunctional hemiaminal moiety. Combination of experimental substituent
      effects with Natural Bond Orbital (NBO) analysis revealed that alkyne
      polarization controls partitioning between these cascades. A particularly
      remarkable transformation leads to the formation of six new bonds at the two
      alkyne carbons due to complete disassembly of the alkyne moiety and formal
      insertion of a nitrogen atom between the two acetylenic carbons of the reactant.
      This reaction offers a new synthetic approach for the preparation of polycyclic
      aromatic amides with a number of possible applications in molecular electronics.
      Another of the newly discovered cascades opens access to substituted analogues of
      Sampangine alkaloids which are known for their antifungal and antimycobacterial
      activity against AIDS-related opportunistic infection pathogens.

PMID- 19585969
TI  - Charge recombination kinetics and protein dynamics in wild type and carotenoid
      less bacterial reaction centers: studies in trehalose glasses.
AB  - The coupling between electron transfer and protein dynamics has been investigated
      in reaction centers (RCs) from the wild type (wt) and the carotenoid-less strain
      R26 of the photosynthetic bacterium Rhodobacter sphaeroides. Recombination
      kinetics between the primary photoreduced quinone acceptor (QA-) and photoxidized
      donor (P+) have been analyzed at room temperature in RCs incorporated into glassy
      trehalose matrices of different water/sugar ratios. As previously found in R26
      RCs, also in the wt RC, upon matrix dehydration, P+QA- recombination accelerates
      and becomes broadly distributed, reflecting the inhibition of protein relaxation
      from the dark-adapted to the light-adapted conformation and the hindrance of
      interconversion between conformational substates. While in wet trehalose matrices
      (down to approximately one water per trehalose molecule) P+QA- recombination
      kinetics are essentially coincident in wt and R26 RCs, more extensive dehydration
      leads to two-times faster and more distributed kinetics in the carotenoid
      containing RC, indicating a stronger inhibition of the internal protein dynamics
      in the wt RC. Coarse-grained Brownian dynamics simulations performed on the two
      RC structures reveal a markedly larger flexibility of the R26 RC, showing that a
      rigid core of residues, close to the quinone acceptors, is specifically softened
      in the absence of the carotenoid. These experimental and computational results
      concur to indicate that removal of the carotenoid molecule has long-range effects
      on protein dynamics and that the structural/dynamical coupling between the
      protein and the glassy matrix depends strongly upon the local mechanical
      properties of the protein interior. The data also suggest that the conformational
      change stabilizing P+QA- is localized around the QA binding pocket.

PMID- 19585970
TI  - Solvent-dependent cage dynamics of small nonpolar radicals: lessons from the
      photodissociation and geminate recombination of alkylcobalamins.
AB  - Time-resolved transient absorption spectroscopy was used to investigate the
      primary geminate recombination and cage escape of alkyl radicals in solution over
      a temperature range from 0 to 80 degrees C. Radical pairs were produced by
      photoexcitation of methyl, ethyl, propyl, hexylnitrile, and adenosylcobalamin in
      water, ethylene glycol, mixtures of water and ethylene glycol, and sucrose
      solutions. In contrast to previous studies of cage escape and geminate
      recombination, these experiments demonstrate that cage escape for these radical
      pairs occurs on time scales ranging from a hundred picoseconds to over a
      nanosecond as a function of solvent fluidity and radical size. Ultrafast cage
      escape (<100 ps) is only observed for the methyl radical where the radical pair
      is produced through excitation to a directly dissociative electronic state. The
      data are interpreted using a unimolecular model with competition between geminate
      recombination and cage escape. The escape rate constant, k(e), is not a simple
      function of the solvent fluidity (T/eta) but depends on the nature of the solvent
      as well. The slope of k(e) as a function of T/eta for the adenosyl radical in
      water is in near quantitative agreement with the slope calculated using a
      hydrodynamic model and the Stokes-Einstein equation for the diffusion
      coefficients. The solvent dependence is reproduced when diffusion constants are
      calculated taking into account the relative volume and mass of both solvent and
      solute using the expression proposed by Akgerman (Akgerman, A.; Gainer, J. L.
      Ind. Eng. Chem. Fundam. 1972, 11, 373-379). Rate constants for cage escape of the
      other radicals investigated are consistently smaller than the calculated values
      suggesting a systematic correction for radical size or coupled radical pair
      motion.

PMID- 19585971
TI  - Novel IgE recognized components of Lolium perenne pollen extract: comparative
      proteomics evaluation of allergic patients sensitization profiles.
AB  - In the last years, proteomic investigation provided a powerful tool in molecular
      characterization of complex allergen sources with relevant implications in both
      diagnosis and immunotherapic treatment of allergies. We followed a proteomic
      approach to characterize ryegrass (Lolium perenne) pollen, a common cause of
      seasonal allergic diseases affecting an increasing part of world population.
      Peptide shotgun experiments performed on nanoLiquid Ultra Pressure Chromatography
      coupled with fast Q-TOF MS-MS/MS acquisition protocols (MS(E)) and 2-DE
      immunoblot combined with MALDI-TOF-TOF analysis allowed the detection of all
      previously identified ryegrass allergens. Comparative analysis of immunoblot
      highlighted a class of patients characterized by a more complex 2-DE pattern
      associated with increased levels of IgE antibodies and by higher susceptibility
      to multiple sensitization toward different allergen sources. Cluster analysis
      revealed that all these patients recognized profilin, considered the main cross
      reactive allergen in grass pollen. Furthermore, mass spectrometry analysis
      revealed the presence of other IgE reactive components in ryegrass pollen that
      might be involved in polysensitization, such as cyclophilin, fructosyltransferase
      and legumin-like protein.

PMID- 19585972
TI  - Umbrella sampling simulations of biotin carboxylase: is a structure with an open
      ATP grasp domain stable in solution?
AB  - Biotin carboxylase is a homodimer that utilizes ATP to carboxylate biotin.
      Studies of the enzyme using X-ray crystallography revealed a prominent
      conformational change upon binding ATP. To determine the importance of this
      closing motion, the potential of mean force with the closure angle as a reaction
      coordinate was calculated using molecular dynamics simulations and umbrella
      sampling for a monomer of Escherichia coli biotin carboxylase in water with
      restraints to simulate attachment to a surface. The result suggests that the most
      stable state for the enzyme is a closed state different from both the ATP-bound
      and open state X-ray crystallography structures. There is also a significant
      motion of a region near the dimer interface not predicted by considering only
      open and closed configurations, which may have implications for the dynamics and
      activity of the dimer.

PMID- 19585973
TI  - Evaluation of range-separated hybrid and other density functional approaches on
      test sets relevant for transition metal-based homogeneous catalysts.
AB  - Homogeneous catalysis by transition metal complexes is challenging to model with
      electronic structure theory. This is due to the large system sizes encountered,
      the wide range of bonding motifs, and the need for accurate treatments of
      reaction kinetics. Range-separated hybrid density functionals have been shown to
      accurately predict a variety of properties in (organic) main group chemistry.
      Here we benchmark representative range-separated hybrids for geometric and
      energetic properties of transition metal complexes. Results from conventional
      semilocal and global hybrid approaches are included for comparison. The range
      separated hybrids' performance, combined with their demonstrated accuracy for
      main group kinetics, makes them promising for applications to homogeneous
      catalysis. Our results also point to the importance of the correlation functional
      in range-separated hybrids.

PMID- 19585974
TI  - Intramolecular charge transfer in 5-methoxy-2-(2-pyridyl)thiazole-derived
      fluorescent molecules with different acceptor or donor substituents.
AB  - On the basis of the rational derivation of 5-methoxy-2-(2-pyridyl)thiazole (2
      MPT), we synthesized a new series of charge-transfer-based fluorescent molecules
      bearing different electronic donors or acceptors. The substituents range from
      strong electronic donors (e.g., amino and hydroxyl groups) to weak donating
      groups (e.g., proton and methyl groups) and electronic acceptors (e.g., pyridine
      ring). Through systematic investigation on the substituent-/polarity-dependent
      spectra (including room-temperature absorption, room-/low-temperature steady
      state fluorescence spectra, and transient fluorescence lifetime characterization)
      and theoretical calculations, the emission properties of MPT derivatives are
      found to be governed by the rotation of the substituent around the triple bond
      axis, which produces distinct intramolecular charge transfer processes in either
      the twisted or planar excited states. The interconversion of excited-state
      geometry triggered by local interactions in polar solvents may produce a
      bathochromic shift of approximately 100 nm in fluorescence spectra. The solution
      state may also affect the ground- and excited-state conformation and hence
      results in the solvent-frozen-point sensitive fluorescence for some of the as
      prepared molecules.

PMID- 19585975
TI  - Statistical recoupling prior to significance testing in nuclear magnetic
      resonance based metabonomics.
AB  - Significance testing is a crucial step in metabolic biomarker recovery from the
      metabolome-wide latent variables computed by multivariate statistical analysis.
      In this study we propose an algorithm based on the landscape of the
      covariance/correlation ratio of consecutive variables along the chemical shift
      axis to restore, prior to significance testing, the spectral dependency and
      recouple variables in clusters which correspond to physical, chemical, and
      biological entities: statistical recoupling of variables (SRV). Variables are
      associated into a series of clusters, which are then considered as individual
      objects for the control of the false discovery rate. Compared to classical
      procedures, it is found that SRV allows efficient recovery of statistically
      significant metabolic variables. The proposed SRV method when associated with the
      Benjamini-Yekutieli correction retains a low level of significant variables in
      the noise areas of the nuclear magnetic resonance (NMR) spectrum, close to that
      observed using the conservative Bonferroni correction (false positive rate),
      while also allowing successful identification of statistically significant
      metabolic NMR signals in cases where the classical procedures of Benjamini
      Yekutieli and Benjamini-Hochberg (false discovery rate) fail. This procedure
      improves the interpretability of latent variables for metabolic biomarker
      recovery.

PMID- 19585976
TI  - Thermodynamic stability and growth of guest-free clathrate hydrates: a low
      density crystal phase of water.
AB  - We use molecular dynamics simulations with the monatomic water (mW) model to
      investigate the phase diagram, metastability, and growth of guest-free water
      clathrates of structure sI and sII. At 1 atm pressure, the simulated guest-free
      water clathrates are metastable with respect to ice and stable with respect to
      the liquid up to their melting temperatures, 245+/-2 and 252+/-2 K for sI and
      sII, respectively. We characterize the growth of the sI and sII water crystals
      from supercooled water and find that the clathrates are unable to nucleate ice,
      the stable crystal. We computed the phase relations of ice, guest-free sII
      clathrate, and liquid water from -1500 to 500 atm. The resulting phase diagram
      indicates that empty sII may be the stable phase of water at pressures lower than
      approximately -1300 atm and temperatures lower than 275 K. The simulations show
      that, even in the region of stability of the empty clathrates, supercooled liquid
      water crystallizes to ice. This suggests that the barrier for nucleation of ice
      is lower than that for clathrates. We find no evidence for the existence of the
      characteristic polyhedral clathrate cages in supercooled extended water. Our
      results show that clathrates do not need the presence of a guest molecule to
      grow, but they need the guest to nucleate from liquid water. We conclude that
      nucleation of empty clathrates from supercooled liquid water would be extremely
      challenging if not impossible to attain in experiments. We propose two strategies
      to produce empty water clathrates in laboratory experiments at low positive
      pressures.

PMID- 19585977
TI  - Jump reorientation of water molecules confined in narrow carbon nanotubes.
AB  - We used molecular dynamics (MD) simulations to study the reorientational dynamics
      of water molecules confined inside narrow carbon nanotubes immersed in a bath of
      water. Our simulations show that the confined water molecules exhibit bistability
      in their reorientational relaxation, which proceeds by angular jumps between the
      two stable states. The angular jump of a water molecule in the bulk involves the
      breaking of a hydrogen bond with one of its neighbors and the formation of a
      hydrogen bond with a different neighbor. In contrast, the angular jump of a
      confined water molecule corresponds to an interchange of the two hydrogen atoms
      that can form a hydrogen bond with the same neighbor. The free energy barrier
      between these two states is a few kBT. The analytic solution of a simplified two
      state jump model that qualitatively explains the reorientational behavior
      observed in simulations is also presented.

PMID- 19585978
TI  - Vibrational and photoionization spectroscopy of neutral valine clusters.
AB  - We report the first observation of infrared (IR) and mass spectra of neutral,
      aliphatic amino acid clusters: the example presented herein is for (valine)(n), n
      = 2-5. The clusters are generated in a supersonic expansion and their IR spectra
      are recorded in various fragment and (valine)(n-1)H(+) (n = 2-5) mass channels.
      The ions are created by single photon ionization with a VUV laser at 118 nm (10.5
      eV/photon) following IR absorption in the single photon energy range 2500-4000
      cm(-1). Mass channels obviously associated with valine clusters lose intensity
      and mass channels associated with valine monomers gain intensity under IR
      irradiation. No free OH modes are identified in any of these spectra suggesting
      that for (valine)(n), n = 1-5, all the OH groups are hydrogen bonded. The
      infrared transition for the hydrogen bonded OH moiety appears as a very broad,
      shifted feature ca. 3000 cm(-1) (approximately 2800 to approximately 3200 cm(
      1)). Free and perturbed NH(2) modes can also be identified in the cluster
      spectra. CH modes ca. 3000 cm(-1) can be identified and appear to be coupled to
      the shifted and broadened OH modes of the clusters. Fragmentation pathways for
      three (valine)(2) isomers under 118 nm ionization are proposed and discussed.

PMID- 19585979
TI  - Fast synthesis, formation mechanism, and control of shell thickness of CuS hollow
      spheres.
AB  - CuS hollow spheres were quickly synthesized under mild conditions with spherical
      aggregates of Cu(2)O nanoparticles as sacrificial templates. The mechanism
      involved in the synthesis process has been studied using transmission electron
      microscopy, high-resolution transmission electron microscopy, scanning electron
      microscopy, X-ray diffraction, thermal gravimetry, and Fourier transform infrared
      spectra. The results show that the formation of loose aggregates of Cu(2)O
      nanoparticles is the key to the fast synthesis of hollow spheres at low
      temperature. The thickness of the shell can be controlled easily by adjusting the
      aggregation degree of the Cu(2)O nanoparticles.

PMID- 19585980
TI  - Cellulosic graft copolymer: poly(methyl methacrylate) with cellulose side chains.
AB  - A cellulose macromonomer, N-(15-methacryloyloxypentadecanoyl)-tri-O-acetyl-beta
      cellulosylamine (CTA-C15-MA (2); M(2)) with number averaged degree of
      polymerization (DP(n)) = 13), was copolymerized with methyl methacrylate (MMA;
      M(1)) to give cellulosic copolymer with CTA side chains, PMMA-g-(CTA-C15) (3-A).
      An absolute molecular weight determined by multiangle laser light scattering
      (MALS; M(w,LS)), degree of polymerization of MMA (X) and CTA-C15-MA (Y) of PMMA-g
      (CTA-C15) (3-A) were determined to be M(w,LS) = 6.30 x 10(4), X = 4.14 x 10(2),
      and Y = 3.86. Cellulose graft copolymer with cellulose side chains, PMMA-g
      (cellulose-C15) (3-H) was successfully obtained after deacetylation of the
      copolymer 3-A. Thermal analysis of copolymers 3-A and 3-H by means of
      differential scanning calorimetry (DSC) measurements revealed that a small amount
      of CTA and cellulose side chains affected thermal properties of the PMMA main
      chain.

PMID- 19585981
TI  - A convergence study of QM/MM isomerization energies with the selected size of the
      QM region for peptidic systems.
AB  - A systematic study of the convergence of QM/MM results with respect to the chosen
      size of the QM region is presented for two examples of peptidic systems. For this
      purpose, we increased the QM region to up to 1637 atoms at the HF/SVP and 383
      atoms at the SOS-AO-MP2/6-31G** level. While the convergence behavior is almost
      independent of the chosen method and basis set, the study clearly shows that for
      the considered proton-transfer energy the QM/MM treatment leads to a
      significantly faster convergence than the pure QM treatment. This behavior can be
      rationalized by the fair description of the surrounding of the active center
      using MM methods, even though the MM description of the active center is not
      adequate in our present case. At the same time, the observed convergence is quite
      insensitive to a variation of charge surroundings in the chosen model peptides.
      Although the QM/MM results do converge much quicker with the system size than the
      pure QM ones, the data show that even for the chosen simple model systems about
      150-300 QM atoms are needed to achieve accuracies in the order of 10 kJ/mol and
      about 300-1000 atoms for an accuracy of 2 kJ/mol with respect to a convergence
      with the QM-region size.

PMID- 19585982
TI  - Structural rearrangements in water viewed through two-dimensional infrared
      spectroscopy.
AB  - Compared with other molecular liquids, water is highly structured because of its
      ability to form up to four hydrogen bonds, resulting in a tetrahedral network of
      molecules. However, this underlying intermolecular structure is constantly in
      motion, exhibiting large fluctuations and reorganizations on time scales from
      femtoseconds to picoseconds. These motions allow water to play a key role in a
      number of chemical and biological processes. By exploiting the fact that the OH
      stretching frequency of dilute HOD in liquid D(2)O is highly dependent upon the
      configuration of the neighbor nearest to the proton, researchers have been able
      to track water's time-dependent structure using two-dimensional infrared (2D IR)
      spectroscopy, which tags molecules at an initial frequency and then watches as
      that frequency evolves with respect to time. Recent advances in molecular
      dynamics simulation techniques allow for the calculation of 2D IR spectra,
      providing an atomistic interpretation tool of 2D IR spectra in terms of the
      underlying dynamics of the liquid. In this Account, we review recent ultrafast 2D
      IR studies at MIT that provide new information on the mechanism of hydrogen-bond
      rearrangements in liquid water. The 2D IR spectra of the OH stretching vibration
      of HOD in D(2)O appear highly asymmetric. In the frequency range indicative of
      hydrogen-bonded molecules (<3300 cm(-1)), the 2D spectra remain fairly compact.
      By contrast, in the frequency range in which molecules having weak or broken
      hydrogen bonds absorb (>3500 cm(-1)), the 2D spectra broaden over a time scale of
      approximately 60 fs, consistent with librations (hindered rotations) of water
      molecules. This broadening indicates that molecules forming weak or broken
      hydrogen bonds are unstable and reorient rapidly to return to a hydrogen-bonded
      configuration. These conclusions are supported by the results of molecular
      dynamics simulations, which suggest that water molecules undergo a large-angle
      reorientation during the course of hydrogen-bond exchange. The transition state
      for hydrogen-bond rearrangements is found to resemble a bifurcated hydrogen bond.
      Roughly half of the hydrogen-bond exchange events in the simulation are found to
      involve the insertion of a water molecule across a hydrogen bond, suggesting that
      hydrogen-bond exchange in water involves the correlated motion of water molecules
      as far away as the second solvation shell. The combination of ultrafast 2D IR
      spectroscopy with simulation-based modeling is leading to self-consistent
      descriptions of the underlying dynamics in liquid water. Moreover, these results
      also demonstrate a more general, unique characteristic of the spectroscopy: if a
      spectral signature of the transition state exists, then 2D IR can effectively
      serve as a transition-state spectroscopy.

PMID- 19585983
TI  - Synthesis, characterization, and study of photoinduced optical anisotropy in
      polyimides containing side azobenzene units.
AB  - In this paper, novel processable aromatic polymers with imide rings and attached
      as side-chain azobenzene units are presented. Polymers differ in the chemical
      structures of chromophores and polymer backbones. Azopolymers were obtained by a
      two-step synthetic approach. This includes the preparation of a precursor
      poly(esterimide) and poly(etherimide) with pendant phenolic hydroxyl groups,
      followed by the covalent bonding of NLO chromophores onto the polyimide backbone
      by the Mitsunobu reaction. The degree of functionalization of polymers was
      estimated by UV-vis spectroscopy. Polymers were characterized and evaluated by FT
      IR, (1)H NMR, X-ray, UV-vis, DSC, and TGA methods. The synthesized polymers
      exhibited glass transition temperatures in the range of 167-228 degrees C,
      thermal stability with decomposition temperatures in the range of 275-446 degrees
      C, and excellent solubilities in common organic solvents. The light-induced
      optical anisotropy was studied in obtained azopolymers with the help of a
      holographic grating recording technique. Two polarization geometries were applied
      for the grating inscription s-s and p-p. The influence of the polarization
      geometry on the diffraction efficiency dynamics and on the depth of the surface
      modulation was not observed, which is different from results reported in the
      literature. Surface relief gratings, which appeared after the light exposure,
      were observed by atomic force microscopy. Additionally, the optical anisotropy in
      poly(esterimide)s was investigated by photoinduced birefringence measurements.
      For the first time, in polyimide with covalently bonded azobenzene derivatives,
      the high photoinduced birefringence (Delta n = 0.01) was measured.

PMID- 19585984
TI  - Ion-rejection, electrokinetic and electrochemical properties of a nanoporous
      track-etched membrane and their interpretation by means of space charge model.
AB  - Due to their straight cylindrical pores, nanoporous track-etched membranes are
      suitable materials for studies of the fundamentals of nanofluidics. In contrast
      to single nanochannels, the nano/micro interface, in this case, can be
      quantitatively considered within the scope of macroscopically 1D models. The
      pressure-induced changes in the concentration of dilute KCl solutions (salt
      rejection phenomenon) have been studied experimentally with a commercially
      available nanoporous track-etched membrane of poly (ethylene terephthalate) (pore
      diameter ca. 21 nm). Besides that, we have also studied the concomitant
      stationary transmembrane electrical phenomenon (filtration potential) and carried
      out time-resolved measurements of the electrical response to a rapid pressure
      switch-off (within 5-10 ms). The latter has enabled us to split the filtration
      potential into the streaming potential and membrane potential components. In this
      way, we could also confirm that the observed nonlinearity of filtration
      potential, as a function of the transmembrane volume flow, was primarily caused
      by the salt rejection. The results of experimental measurements have been
      interpreted by means of a space charge model with the surface charge density
      being a single fitting parameter (the pore size was estimated from the membrane
      hydraulic permeability). By using the surface charge density fitted to the salt
      rejection data, the results of electrical measurements could be reproduced
      theoretically with a typical accuracy of 10% or better. Taking into account the
      simplifications made in the modeling, this accuracy appears to be good and
      confirms the quantitative applicability of the basic concept of space charge
      model to the description of transport properties of dilute electrolyte solutions
      in nanochannels of ca. 20 nm.

PMID- 19585985
TI  - DNA profiling using solid-state nanopores: detection of DNA-binding molecules.
AB  - We present a novel single-molecule method for rapidly evaluating small-molecule
      binding to individual DNA molecules using nanopores fabricated in ultrathin
      silicon membranes. A measurable shift in the residual ion current through a
      approximately 3.5 nm pore results from threading of a dye-intercalated DNA
      molecule, as compared to the typical residual current of native DNA. The average
      level of the residual current can be used to directly quantify the fraction of
      bound molecules to DNA, providing a new way to determine binding isotherms.
      Spatial sensitivity is also demonstrated by designing a two-segment DNA molecule
      that contains small-molecule binding sites in one of its two segments.
      Translocations of such molecules exhibit two current levels upon incubation with
      a DNA-binding dye, caused by selectively bound dye in one of the DNA segments.
      Our results, as shown here with four different dyes, coincide well with bulk
      fluorescence measurements performed under identical conditions. The nanopore
      approach for "reading-out" molecular binding along a DNA molecule, combined with
      the miniscule amounts of DNA required and the potential for scalability using
      nanopore arrays, provide a novel platform for future applications in analytical
      drug screening.

PMID- 19585986
TI  - Highly enantioselective synthesis of beta-amidophenylthioethers by
      organocatalytic desymmetrization of meso-aziridines.
AB  - The desymmetrization of N-acylaziridines with Me(3)SiSPh, catalyzed by
      commercially available (R) and (S)-VAPOL hydrogen phosphate, produced beta-(N
      acylamino)phenylthioethers in a highly enantioselective and efficient manner (78
      99% ee). The selection of the suitable aziridine/nucleophile/catalyst molar ratio
      is crucial to obtain high ee's.

PMID- 19585987
TI  - Aggregation of gold nanoframes reduces, rather than enhances, SERS efficiency due
      to the trade-off of the inter- and intraparticle plasmonic fields.
AB  - It is usually observed and understood that aggregation of silver and gold solid
      nanoparticles gives rise to enhanced SERS spectra due to the increased plasmon
      field between the particles. In the present work, we observed that the increase
      of aggregation of Langmuir-Blodgett assembled 80 nm gold nanoframe particles
      reduces the efficiency of the surface-enhanced Raman spectra of adsorbed
      thiophenol molecules. Using discrete dipole approximation simulation of the
      plasmonic fields of a pair of nanoframes as a function of their interparticle
      separation, it is found that at large separation the fields inside the cavities
      are stronger than those outside. As the interpair separation decreases, the gain
      in the interparticle field does not make up for the loss in the field within the
      cavities, supporting the observation of the decrease in the SERS intensity with
      aggregation.

PMID- 19585988
TI  - Identifying the local structures formed during lithiation of the conversion
      material, iron fluoride, in a Li ion battery: a solid-state NMR, X-ray
      diffraction, and pair distribution function analysis study.
AB  - The structural transformations that occur when FeF(3) is cycled at room
      temperature in a Li cell were investigated using a combination of X-ray
      diffraction (XRD), pair distribution function (PDF) analysis, and magic-angle
      spinning NMR spectroscopy. Two regions are seen on discharge. The first occurs
      between Li = 0 and 1.0 and involves an insertion reaction. This first region
      actually comprises two steps: First, a two-phase reaction between Li = 0 and 0.5
      occurs, and the Li(0.5)FeF(3) phase that is formed gives rise to a Li NMR
      resonance due to Li(+) ions near both Fe(3+) and Fe(2+) ions. On the basis of the
      PDF data, the local structure of this phase is closer to the rutile structure
      than the original ReO(3) structure. Second, a single-phase intercalation reaction
      occurs between Li = 0.5 and 1.0, for which the Li NMR data indicate a progressive
      increase in the concentration of Fe(2+) ions. In the second region, the
      conversion reaction, superparamagnetic, nanosized ( approximately 3 nm) Fe metal
      is formed, as indicated by the XRD and NMR data, along with some LiF and a third
      phase that is rich in Li and F. The charge process involves the formation of a
      series of intercalation phases with increasing Fe oxidation state, which, on the
      basis of the Li NMR and PDF data, have local structures that are similar to the
      intercalation phases seen during the first stage of the discharge process. The
      solid-state NMR and XRD results for the rutile phase FeF(2) are presented for
      comparison, and the data indicate that an insertion reaction also occurs, which
      is accompanied by the formation of LiF. This is followed by the formation of Fe
      nanoparticles and LiF via a conversion reaction.

PMID- 19585989
TI  - Covalent inhibition of bacterial quorum sensing.
AB  - Chemical coordination of gene expression among bacteria as a function of
      population density is regulated by a mechanism known as 'quorum sensing' (QS). QS
      in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in
      immunocompromised patients, is mediated by binding of the transcriptional
      activator, LasR, to its ligand, 3-oxo-C(12)-HSL, leading to population-wide
      secretion of virulence factors and biofilm formation. We have targeted QS in P.
      aeruginosa with a set of electrophilic probes designed to covalently bind Cys79
      in the LasR binding pocket, leading to specific inhibition of QS-regulated gene
      expression and concomitant reduction of virulence factor secretion and biofilm
      formation. This first example of covalent modification of a QS receptor provides
      a new tool to study molecular mechanisms of bacterial group behavior and could
      lead to new strategies for targeting bacterial virulence.

PMID- 19585990
TI  - A Crystallizable dinuclear tuck-in-tuck-over tuck-over dialkyl Tren uranium
      complex and double dearylation of BPh(4)(-) to give the BPh(2)-functionalized
      metallocycle [U{N(CH(2)CH(2)NSiMe(3))(2)(CH(2)CH(2)NSiMe(2)CHBPh(2))}(THF)].
AB  - The unprecedented formation of a dinuclear tuck-in-tuck-over tuck-over dialkyl
      Tren-uranium(IV) complex and the first example of double dearylation of BPh(4)(-)
      in a molecular context to give a BPh(2)-functionalized uranium metallocycle are
      reported.

PMID- 19585991
TI  - Noninnocent behavior of ancillary ligands: apparent trans coupling of a saturated
      N-heterocyclic carbene unit with an ethyl ligand mediated by nickel.
AB  - Oxidative addition of the tridentate N-heterocyclic carbene (NHC) diphosphine
      ligand precursor ([PCP]H)PF(6) (1) {[PCP] = o-(i)Pr(2)PC(6)H(4)(NC(3)H(4)N)o
      C(6)H(4)P(i)Pr(2)} to Ni(COD)(2) results in the formation of the nickel(II)
      hydride complex ([PCP]NiH)PF(6) (2). This hydride undergoes a rapid reaction with
      ethylene to generate a nickel(0) complex in which an ethyl group has been
      transferred to the carbene carbon of the original NHC-diphosphine ligand. If the
      first intermediate is the anticipated square-planar nickel(II) ethyl species,
      then the formation of the product would require a process that involves a trans C
      C coupling of the NHC carbon and a presumed Ni-ethyl intermediate. Deuterium
      labeling studies provide evidence for migratory insertion of the added ethylene
      into the Ni-H bond rather than into the Ni-carbene linkage; this is based on the
      observed deuterium scrambling, which requires reversible beta-elimination, alkene
      rotation, and hydride readdition. However, density functional theory studies
      suggest that a key intermediate is an agostic ethyl species that has the Ni-C
      bond cis to the NHC unit. A possible transition state containing two cis-disposed
      carbon moieties was also identified. Such a process represents a new pathway for
      catalyst deactivation involving NHC-based metal complexes.

PMID- 19585992
TI  - Defining active catalyst structure and reaction pathways from ab initio molecular
      dynamics and operando XAFS: dehydrogenation of dimethylaminoborane by rhodium
      clusters.
AB  - We present the results of a detailed operando XAFS and density functional theory
      (DFT)-based ab initio molecular dynamics (AIMD) investigation of a proposed
      mechanism of the dehydrogenation of dimethylaminoborane (DMAB) by a homogeneous
      Rh(4) cluster catalyst. Our AIMD simulations reveal that previously proposed Rh
      structures, based on XAFS measurements, are highly fluxional, exhibiting both
      metal cluster and ligand isomerizations and dissociation that can only be
      accounted for by examining a finite temperature ensemble. It is found that a
      fluxional species Rh(4)(H(2)BNMe(2))(8)(2+) is fully compatible with operando
      XAFS measurements, suggesting that this species may be the observed catalyst
      resting state. On the basis of this assignment, we propose a mechanism for
      catalytic DMAB dehydrogenation that exhibits an energy barrier of approximately
      28 kcal/mol.

PMID- 19585994
TI  - The standard partial molar volumes of ions in solution. Part 4. Ionic volumes in
      water at 0-100 degrees C.
AB  - The standard partial molar volumes of 10 univalent and 5 divalent ions in water
      over the temperature range of its existence as a liquid at ambient pressure (0
      100 degrees C) are fitted as the sum of their (negative) electrostrictive volumes
      and intrinsic volumes, including disordered water. The former are obtained from
      the shell-by-shell calculation of the electrostriction according to Marcus and
      Hefter that takes into account the mutual dependence of the relative permittivity
      and the electrical field strength of the water around the ion. This calculation
      yields also the spatial extension of the dielectrically saturated region around
      the ions. The average molar electrostriction of the water in the vicinity of the
      ions is also calculated and leads to estimated hydration numbers.

PMID- 19585993
TI  - Trypsin from the pyloric ceca of pectoral rattail (Coryphaenoides pectoralis):
      purification and characterization.
AB  - Trypsin from the pyloric ceca of pectoral rattail (Coryphaenoides pectoralis) was
      purified and characterized. Purification was carried out by ammonium sulfate
      precipitation, followed by column chromatographies on Sephacryl S-200, DEAE
      cellulose and Sephadex G-50. The enzyme was purified 89-fold with a yield of
      2.2%. Purified trypsin had an apparent molecular weight of 24 kDa when analyzed
      using SDS-PAGE and size exclusion chromatography. Optimal profiles of pH and
      temperature of the enzyme were 8.5 and 45 degrees C, respectively, using N(alpha)
      p-tosyl-l-arginine methyl ester hydrochloride as a substrate. It was stable in a
      wide pH range of 6-11 but unstable at a temperature greater than 40 degrees C.
      Trypsin was stabilized by calcium ion. The activity of purified trypsin was
      effectively inhibited by soybean trypsin inhibitor and TLCK and was partially
      inhibited by EDTA. Activity continuously decreased with increasing NaCl
      concentration (0-30%). The kinetic trypsin constants K(m) and K(cat) were 0.15 mM
      and 210 s(-1), respectively, while the catalytic efficiency (K(cat)/K(m)) was
      1400 s(-1) mM(-1). The N-terminal amino acid sequence of trypsin was determined
      to be 12 residues (IVGGYECQEHSQ), and the sequence showed high homology to other
      fish trypsins.

PMID- 19585995
TI  - Mild and selective deuteration and isomerization of alkenes by a bifunctional
      catalyst and deuterium oxide.
AB  - H/D exchange is achieved at allylic positions of alkenes using D(2)O in acetone
      and alkene isomerization catalyst 1, which features a bifunctional
      imidazolylphosphine. The basic nitrogen of the latter is thought to deprotonate
      an alkene substrate coordinated to the CpRu center; at this stage the protonated
      nitrogen could undergo H/D exchange with deuterium oxide. An exceptional degree
      of deuteration is achieved at positions accessible to isomerization, with a high
      degree of control. Using biphasic settings one can literally wash out reactive
      protons on the substrate without using organic solvents.

PMID- 19585996
TI  - [Ln(DPA)(3)](3-) is a convenient paramagnetic shift reagent for protein NMR
      studies.
AB  - Paramagnetic lanthanide ions present outstanding tools for structural biology by
      NMR spectroscopy. Here we show that the 3:1 complexes between dipicolinic acid
      and lanthanides are paramagnetic reagents which can site-specifically bind to a
      wide range of proteins without formation of a covalent bond. The observed
      pseudocontact shifts can be interpreted by a single magnetic susceptibility
      anisotropy tensor, enabling its use for structure refinements. The resonance
      assignment of the paramagnetic spectrum is greatly facilitated by the rapid
      exchange between bound and free protein, leading to gradual chemical shift
      changes as the protein is titrated with the paramagnetic dipicolinic acid
      complex. The association with the paramagnetic lanthanide leads to weak molecular
      alignment in a magnetic field so that the reagents can be used for the
      measurement of residual dipolar couplings without the need of protein
      modification or anisotropic alignment media. The protein samples can be recovered
      by simple dialysis.

PMID- 19585997
TI  - Label-free DNA detection on nanostructured Ag surfaces.
AB  - The dramatic local electric-field enhancement property of Ag nanoparticles was
      used as the basis to significantly increase the signal output of a novel label
      free (or "self-labeled") fluorescence-based DNA detection system. In response to
      identical amounts of analyte, nanostructured Ag substrates provided a
      posthybridization fluorescent sensor response over 10-fold larger than the
      response from planar Au substrates. Detection performance strongly depended upon
      the Ag substrate roughness. Consistent with work by others on metal-enhanced
      fluorescence, fluorescence intensity also depended strongly on the distance
      between the fluorophore and the Ag substrate surface. Adjusting the surface
      roughness, amount of the Ag deposited on the surface, and the DNA probe length
      allowed for production of an optimized response. In addition to constituting a
      novel label-free DNA sensor, we anticipate that these structures will provide a
      unique platform for testing concepts in plasmonics.

PMID- 19585998
TI  - Cytotoxic triterpenoids from the rhizomes of Astilbe chinensis.
AB  - Six new triterpenoids (1-6) with a carboxylic acid functionality at C-27 were
      isolated from the rhizomes of a Korean native perennial herb, Astilbe chinensis,
      along with nine known triterpenoids. The structures of 1-6 were elucidated on the
      basis of spectroscopic data interpretation. All compounds isolated were evaluated
      for cytotoxic effects against a small panel of human cancer lines.

PMID- 19585999
TI  - Reversible thiazolidine exchange: a new reaction suitable for dynamic
      combinatorial chemistry.
AB  - New dynamic combinatorial libraries (DCLs) were generated using the reversible
      aminothiol exchange reaction of thiazolidines and aromatic aldehydes. The
      reaction proceeded in aqueous buffered media at pH 4 and room temperature to
      generate thermodynamically controlled mixtures of heterocycles. The synthesis of
      an enantiomerically pure thiazolidinyloxazolidine is also reported. The
      oxazolidine moiety could be exchanged in CH(2)Cl(2) in the presence of catalytic
      p-TsOH.

PMID- 19586000
TI  - Zirconium-mediated selective synthesis of 1,2,4,5-tetrasubstituted benzenes from
      two silyl-substituted alkynes and one internal alkyne.
AB  - Selective synthesis of 1,2,4,5-tetrasubstituted benzenes was achieved via
      formation of 2,5-bis(trimethylsilyl)zirconacyclopentadienes from 2 equiv of TMS
      substituted alkynes with Cp(2)ZrBu(2) and Cu-mediated formation of 1,4
      disilylbenzene by cycloaddition of zirconacyclopentadienes to disubstituted
      alkynes. Preparation of 1,2,3,4,9,10-hexasubstituted pentacene and 2,3,6,11
      tetrasubstituted naphthacene derivatives were demonstrated by a homologation or
      coupling method using tetrasubstituted benzene.

PMID- 19586001
TI  - Total synthesis of (-)-zampanolide and questionable existence of (-)-dactylolide
      as the elusive biosynthetic precursor of (-)-zampanolide in an Okinawan sponge.
AB  - A new and concise total synthesis of (-)-zampanolide, (-)-1, and (-)-dactylolide,
      (-)-2, is described. Synthetic highlights include (i) a mild Horner-Wadsworth
      Emmons reaction providing the seco acid, (ii) an unusual stepwise cross-coupling
      reaction of a 1,1-dibromodiene with inversion of olefin geometry, and (iii)
      specific O-Michael reaction conditions using catalytic LHMDS with TMEDA for the
      synthesis of functionalized 2,6-cis-tetrahydropyran. A marine sponge extract was
      analyzed for the presence of (-)-2 as the biosynthetic precursor of (-)
      zampanolide.

PMID- 19586002
TI  - Molecular dynamics study of a polymeric reverse osmosis membrane.
AB  - Molecular dynamics (MD) simulations are used to investigate the properties of an
      atomic model of an aromatic polyamide reverse osmosis membrane. The monomers
      forming the polymeric membrane are cross-linked progressively on the basis of a
      heuristic distance criterion during MD simulations until the system
      interconnectivity reaches completion. Equilibrium MD simulations of the hydrated
      membrane are then used to determine the density and diffusivity of water within
      the membrane. Given a 3 MPa pressure differential and a 0.125 microm width
      membrane, the simulated water flux is calculated to be 1.4x10(-6) m/s, which is
      in fair agreement with an experimental flux measurement of 7.7x10(-6) m/s.

PMID- 19586003
TI  - Molecules with all triple bonds: OCBBCO, N2BBN2, and [OBBBBO](2-).
AB  - DFT calculations at the BP86/TZ2P level have been carried out for the compounds
      OCBBCO, N(2)BBN(2), and [OBBBBO](2-). The calculations predict very short
      distances and large bond dissociation energies for the central B-B bonds. The
      nature of the bonding situation was investigated with an energy decomposition
      analysis. It shows that the central boron-boron bonds are genuine triple bonds.
      The pi-bonding contributes between 38-40% to the total orbital interactions of
      the B[triple bond]B bonds. The compounds can be considered as donor-acceptor
      complexes L-->BB<--L between the central B(2) moiety in the third
      [(3)(1)Sigma(g)(+)] excited state and the ligands L = CO, N(2), BO(-). The pi
      backdonation L<--BB-->L for L = CO, N(2) is very strong, which suggests that the
      latter bonds should also be considered as triple bonds. The pi-bonding in [OB<-
      BB-->BO](2-) is weaker, which makes the latter bonds borderline cases for triple
      bonds. The triple-bond character explains the very large bond dissociation
      energies for the LB-BL and L-BB-L bonds.

PMID- 19586004
TI  - Magnetically induced current densities in aromatic, antiaromatic, homoaromatic,
      and nonaromatic hydrocarbons.
AB  - The magnetically induced current densities for ring-shaped hydrocarbons are
      studied at the density functional theory (DFT) and second-order Moller-Plesset
      (MP2) levels using gauge-including atomic orbitals. The current densities are
      calculated using the gauge-including magnetically induced current approach. The
      calculations show that all studied hydrocarbon rings sustain strong diatropic and
      paratropic ring currents when exposed to an external magnetic field, regardless
      whether they are unsaturated or not. For nonaromatic rings, the strength of the
      paratropic current flowing inside the ring is as large as the diatropic one
      circling outside it, yielding a vanishing net ring current. For aromatic
      molecules, the diatropic current on the outside of the ring is much stronger than
      the paratropic one inside, giving rise to the net diatropic ring current that is
      typical for aromatic molecules. For antiaromatic molecules, the paratropic ring
      current contribution inside the ring dominates. For homoaromatic molecules, the
      diatropic current circles at the periphery of the ring. The ring current is split
      at the CH(2) moiety; the main fraction of the current flow passes outside the
      CH(2) at the hydrogens, and some current flows inside the carbon atom. The
      diatropic current does not take the through-space short-cut pathway, whereas the
      paratropic current does take that route. Calculations of the ring-current profile
      show that the ring current of benzene is not transported by the pi electrons on
      both sides of the molecular ring. The strongest diatropic ring current flows on
      the outside of the ring and in the ring plane. A weaker paratropic current
      circles inside the ring with the largest current density in the ring plane. Due
      to the ring strain, small unconjugated and saturated hydrocarbon rings sustain a
      strong ring current which could be called ring-strain current. Nuclear magnetic
      shieldings calculated for 1,3,5-cycloheptatriene and homotropylium at the DFT and
      MP2 levels agree well with experimental values.

PMID- 19586006
TI  - Reduction of titanium dioxide to metallic titanium conducted under the autogenic
      pressure of the reactants.
AB  - We report on a reaction to convert titanium dioxide to titanium. The reduction
      reaction was done under the autogenic pressure of the reactants at 750 degrees C
      for 5 h. The MgO, a by-product, was removed by acids to obtain pure metallic
      titanium.

PMID- 19586005
TI  - New approaches to the characterization of carbon paste electrodes using the ohmic
      resistance effect and qualitative carbon paste indexes.
AB  - In this article, some new approaches to characterize the carbon paste mixtures
      and the respective carbon paste electrodes (CPEs) are presented, discussed, and
      critically evaluated. Particular attention has been paid to the changes of the
      ohmic resistance, relative to the dependence on composition of the CPE, the
      materials used, the time, and the position of storage. Four types of carbon
      pastes were examined, and for the interpretation of experimental data, a new
      simple model of "close-packing of spheres" has been applied. This model resembles
      the percolation theory for solid matter. In our case, however, it is possible to
      explain not only the "bent" or "broken" shape of the dependence of the electrode
      resistance upon the binder:carbon ratio and the corresponding electrochemical
      current response, but also differences caused by various material used and three
      various effects observed during the electrode aging. Furthermore, the report
      presents the significance of practical utilization of the recently introduced
      carbon paste index (denoted as chi(CPE)), which is a qualitative hitherto unused
      factor based on the evaluation of cyclic voltammograms for standard redox systems
      (e.g., [Fe(CN)(6)](3-/4-)) and specifying the electrochemical properties of a
      CPE. Some problems connected with homogeneity and stability of carbon pastes,
      their handling, storage, or eventual aging effects are also discussed.

PMID- 19586007
TI  - Cyclic arsenic-nitrogen cations.
AB  - A series of different cyclo-diarsa-diazenium salts bearing several bulky groups
      such as supermesityl (Mes* = 2,4,6-tBu(3)C(6)H(2)) and m-terphenyl (2,6-Mes(2)
      C(6)H(3), Mes = 2,4,6-Me(3)C(6)H(2)) and anions such as triflate (OTf =
      SO(3)CF(3) = trifluoromethylsulfonate) and tetrachloridogallate (GaCl(4)(-)) were
      synthesized and fully characterized. The novel 1-chloro-cyclo-1,3-diarsa-2,4
      diazenium cation represents the first example of a binary cyclic As(III)/N four
      membered heterocyclic cation, with a di- and tricoordinated As atom and a
      delocalized pi bond along the NAs((+))N unit. The addition of excess Me(3)SiN(3)
      yields the fully characterized cationic arsenic azide, 1-azido-cyclo-1,3-diarsa
      2,4-diazenium-mu-azido-hexachlorido-digallate. The Cl(-)/N(3)(-) exchange is
      triggered by the action of the Lewis acid GaCl(3). Depending on the Me(3)SiN(3)
      stoichiometry, different mu-azido-hexachlorido-digallate salts with either 1
      chloro- or 1-azido-cyclo-1,3-diarsa-2,4-diazenium cations or even a mixture of
      both are observed. Moreover, it was of special interest to study the distances
      between the cationic arsenic center and the anion in cyclo-diarsa-diazenium
      salts. A correlation between the color of the salt and the anion/cation distance,
      ranging between 2 and 8 A in cyclo-diarsa-diazenium salts of the type
      [R(2)N(2)As(2)Y](+)X(-) depending on the bulky group R (R = Mes*, Ter), the
      substituent Y (Y = Cl, N(3), OTf), and the anion X(-) (X = OTf, GaCl(4), Cl(3)Ga
      N(3)-GaCl(3)), was established.

PMID- 19586008
TI  - Integrated microfluidic electrochemical DNA sensor.
AB  - Effective systems for rapid, sequence-specific nucleic acid detection at the
      point of care would be valuable for a wide variety of applications, including
      clinical diagnostics, food safety, forensics, and environmental monitoring.
      Electrochemical detection offers many advantages as a basis for such platforms,
      including portability and ready integration with electronics. Toward this end, we
      report the Integrated Microfluidic Electrochemical DNA (IMED) sensor, which
      combines three key biochemical functionalities--symmetric PCR, enzymatic single
      stranded DNA generation, and sequence-specific electrochemical detection--in a
      disposable, monolithic chip. Using this platform, we demonstrate detection of
      genomic DNA from Salmonella enterica serovar Typhimurium LT2 with a limit of
      detection of <10 aM, which is approximately 2 orders of magnitude lower than that
      from previously reported electrochemical chip-based methods.

PMID- 19586009
TI  - Synthesis of highly enantioenriched chiral alpha-aminoorganotins via
      diastereoselective ring opening of chiral N-(arenesulfonyl) 2
      tributylstannyloxazolidines.
AB  - trans-N-(Arenesulfonyl)-2-tributylstannyloxazolidines derived from (R)
      phenylglycinol were diastereoselectively ring-opened by soft organometallic
      reagents in the presence of BF(3).OEt(2). Both higher order organocuprates and
      allyltributyltin afforded the desired products in good-to-excellent yields and
      high diastereoselectivities (dr up to 99/1). The stereochemical assignments of
      tributylstannyl-beta-aminoalcohols were firmly established from NMR data and
      after determination of several radiocrystallographic structures. Mechanisms were
      proposed in order to rationalize the observed selectivities.

PMID- 19586010
TI  - Stereoselective synthesis of anti-N-protected 3-amino-1,2-epoxides by
      nucleophilic addition to N-tert-butanesulfinyl imine of a glyceraldehyde synthon.
AB  - A di-O-TBS protected glyceraldehyde synthon was condensed with Ellman's reagent
      to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common
      intermediate for the stereoselective introduction of various R groups. The Ellman
      adducts were converted to useful multifunctional intermediates 18a-i in one pot.
      The alcohols 18a-i were efficiently elaborated to both known and novel anti-N
      protected-3-amino-1,2-epoxides in two steps. Compound 2a is a key intermediate
      toward HIV protease inhibitors.

PMID- 19586011
TI  - Turning a mesophilic protein into a thermophilic one: a computational approach
      based on 3D structural features.
AB  - In spite of considerable improvement of our understanding of factors responsible
      for protein thermostability, rational designing of thermostable variants of
      mesophilic proteins is not yet fully established. The present paper describes an
      effective computational strategy that we have developed to identify the most
      suitable mutations converting a chosen mesophilic protein into a thermophilic one
      starting from its 3D structure. The approach is based on the concept that
      stabilization of several surface residues should enhance the global stability of
      the protein. The method relies on the estimation of electrostatic and van der
      Waals interactions in computing the interaction among the side chains of
      individual residues and the rest of the protein. The polar or charged residues
      whose side chains interact weakly with the rest of the original protein are
      identified first. Then, for each such identified residue (A), another residue (B)
      in its spatial vicinity is identified. The side chain of the residue (B) is then
      replaced by a suitable conformer of a residue that is electrostatically
      complementary to the residue (A) to enhance local interactions and hence the
      stability of the protein. The steric effect is taken care of through van der
      Waals interactions. We reject the mutations that improve interactions only
      locally along the sequence as it is unlikely to enhance the global stability of
      the 3D architecture. We use the difference in self-energies (DeltaEself) as a
      measure of the stability difference between the original and its mutant variant.
      This paper presents two test cases with demonstration of the enhanced stability
      of such mutated proteins and validates the strategy by considering five
      experimentally known thermophilic-mesophilic protein pairs.

PMID- 19586012
TI  - Bis sigma-bond dihydrogen and borane ruthenium complexes: bonding nature,
      catalytic applications, and reversible hydrogen release.
AB  - Hydrogen, the simplest element in the periodic table, plays a tremendous role in
      organic and inorganic chemistry. For years, it was inconceivable that dihydrogen
      could be bound to a metal center without breaking the H-H bond. Thus, oxidative
      addition of H(2) was universally recognized as a key elementary step in
      hydrogenation processes. In 1984, Kubas and co-workers reported the first example
      of a complex in which dihydrogen was coordinated to a metal center without
      breaking of the H-H bond. This opened a new area in coordination chemistry: sigma
      complexes were born, complementing the well-known Werner-type family of
      complexes. Since then, hundreds of stable dihydrogen complexes have been
      isolated, and their properties have been investigated in detail. By comparison,
      very little information is available for the analogous class of sigma-borane
      complexes, in which sigma-H-B bonds are complexed to a metal (in the manner of H
      H bonds in sigma-dihydrogen complexes). Since the first example published in 1996
      by Hartwig and co-workers, very few sigma-borane complexes have been isolated.
      Scientists have maintained a continuous interest in catalytic hydrogenation
      reactions. Almost a century ago, in 1912, Paul Sabatier, the father of the
      hydrogenation process, received the Nobel prize, and the selection of Noyori and
      Knowles in 2001 for their studies on enantioselective catalyzed hydrogenations
      amply demonstrates the ongoing importance of the field. Moreover, during the past
      decade, dihydrogen has attracted considerable attention as a possible "fuel of
      the future". This endeavor has furthered interest in sigma-borane complexes, as
      more and more evidence links their chemistry to that of amine-borane derivatives.
      Indeed, ammonia-borane (NH(3)BH(3)) is attracting significant interest for
      hydrogen storage applications. One of the main limitations is the lack of
      reversibility associated with the production of dehydrogenated (BNH)(x)
      materials. Of major importance will be a better understanding of the coordination
      of H(2) to a metal center, and more generally of the coordination of H-E bonds (E
      = B, C), which are likely to play a critical role in the reversible
      dehydrogenation process. In this Account, we review our recent results in the
      field of dihydrogen and borane activation, with a specific focus on the problem
      of reversible dehydrogenation pathways. We concentrate on the chemistry of
      ruthenium complexes incorporating two sigma-ligands: either two dihydrogen or two
      sigma-B-H bonds. We describe our synthetic strategies to prepare such unusual
      structures. Their characterization is discussed in detail, highlighting the
      importance of an experimental and theoretical approach (NMR, structural, and
      theoretical studies). Some catalytic applications are discussed and put into
      context, and their reactivity toward reversible hydrogen release is detailed.

PMID- 19586013
TI  - Efficient guest inclusion by beta-cyclodextrin attached to the ends of DNA
      oligomers upon hybridization to various DNA conjugates.
AB  - Two types of 5'-beta-CyD-DNA conjugates were synthesized using two different
      strategies and were hybridized with cDNA conjugates bearing various possible
      guest compounds at the 3' ends. One of the beta-CyD conjugates was synthesized on
      the basis of solid-phase postmodification of DNA with a monoamino-beta-CyD
      derivative on a synthesis column for automated DNA synthesis. The other beta-CyD
      conjugate was synthesized by the solution-phase coupling of DNA with a
      monomercapto-beta-CyD derivative using a heterobifunctional cross-coupling
      reagent. When these 5'-beta-CyD-DNA conjugates were hybridized with cDNA
      conjugates bearing 1-adamantaneacetic acid at the 3' ends, significant
      stabilization of the duplexes was observed as compared with the control duplex
      without beta-CyD. Duplexes of 5'-beta-CyD-DNA conjugates and complementary 3'
      dansyl-glycine-DNA conjugates were also moderately stabilized. Thermodynamic
      measurements revealed that the host-guest inclusion interactions between beta-CyD
      and 1-adamantaneacetic acid or dansyl-glycine are roughly as strong as those
      found in bulk solution even if they are tethered to the ends of the DNA.

PMID- 19586014
TI  - In situ phase separation following dehydration in bimetallic sulfates: a variable
      temperature X-ray diffraction study.
AB  - Phase separation resulting in a single-crystal-single-crystal transition
      accompanied by a polycrystalline phase following the dehydration of hydrated
      bimetallic sulfates [Na(2)Mn(1.167)(SO(4))(2)S(0.33)O(1.167) x 2 H(2)O and
      K(4)Cd(3)(SO(4))(5) x 3 H(2)O] has been investigated by in situ variable
      temperature single-crystal X-ray diffraction. With two examples, we illustrate
      the possibility of generating structural frameworks following dehydration in
      bimetallic sulfates, which refer to the possible precursor phases at that
      temperature leading to the mineral formation. The room-temperature structure of
      Na(2)Mn(1.167)(SO(4))(2)S(0.33)O(1.167) x 2 H(2)O is trigonal, space group R3. On
      heating the crystal in situ on the diffractometer, the diffraction images display
      spherical spots and concentric rings suggesting phase separation, with the
      spherical spots getting indexed in a monoclinic space group, C2/c. The structure
      determination based on this data suggests the formation of Na(2)Mn(SO(4))(2).
      However, the diffraction images from concentric rings could not be indexed. In
      the second example, the room-temperature structure is determined to be
      K(4)Cd(3)(SO(4))(5) x 3 H(2)O, crystallizing in a monoclinic space group,
      P2(1)/n. On heating the crystal in situ, the diffraction images collected also
      have both spherical spots and diffuse rings. The spherical spots could be indexed
      to a cubic crystal system, space group P2(1)3, and the structure is
      K(2)Cd(2)(SO(4))(3). The possible mechanism for the phase transition in the
      dehydration regime resulting in this remarkable single-crystal to single-crystal
      transition with the appearance of a surrogate polycrystalline phase is proposed.

PMID- 19586015
TI  - "Four-potential" ferrocene labeling of PNA oligomers via click chemistry.
AB  - The scope of the Cu(I)-catalyzed [2 + 3] azide/alkyne cycloaddition (CuAAC, click
      chemistry) as a key reaction for the conjugation of ferrocene derivatives to N
      terminal functionalized PNA oligomers is explored herein (PNA: peptide nucleic
      acid). The facile solid-phase synthesis of N-terminal azide or alkyne
      functionalized PNA oligomer precursors and their cycloaddition with
      azidoferrocene, ethynylferrocene, and N-(3-ethylpent-1-yn-3-yl)ferrocene
      carboxamide (DEPA-ferrocene) on the solid phase are presented. While the click
      reaction with azidomethylferrocene worked equally well, the ferrocenylmethyl
      group is lost from the conjugate upon acid cleavage. However, the desired product
      was obtained via a post-SPPS conversion of the alkyne-PNA oligomer with
      azidomethylferrocene in solution. The synthesis of all ferrocene-PNA conjugates
      (trimer t(3)-PNA, 3, 4, 5, 6; 12mer PNA, 10 - t c t a c a a g a c t c, 11 - t c t
      a c c g t a c t c) succeeded with excellent yields and purities, as determined by
      mass spectrometry and HPLC. Electrochemical studies of the trimer Fc-PNA
      conjugates 3, 4, 5, and 6 with four different ferrocene moieties revealed quasi
      reversible redox processes of the ferrocenyl redox couple Fc(0/+) and
      electrochemical half-wave potentials in a range of E(1/2) = -20 mV to +270 mV vs
      FcH(0/+) (Fc: ferrocenyl, C(10)H(9)Fe). The observed potential differences
      DeltaE(1/2)(min) are always greater than 60 mV for any given pair of Fc-PNA
      conjugates, thus allowing a reliable differentiation with sensitive
      electrochemical methods like e.g. square wave voltammetry (SWV). This is the
      electrochemical equivalent of "four-color" detection and is hence denoted "four
      potential" labeling. Preparation and electrochemical investigation of the set of
      four structurally different and electrochemically distinguishable ferrocenyl
      groups conjugated to PNA oligomers, as exemplified by the conjugates 3, 4, 5, and
      6, demonstrates the scope of the azide/alkyne cycloaddition for the labeling of
      PNA with electrochemically active ferrocenyl groups. Furthermore, it provides a
      PNA-based system for the electrochemical detection of single-nucleotide
      polymorphism (SNP) in DNA/RNA.

PMID- 19586016
TI  - Effect of dynamic exclusion duration on spectral count based quantitative
      proteomics.
AB  - To increase proteome coverage, dynamic exclusion (DE) is a widely used tool. When
      DE is enabled, more proteins can be identified, although the total spectral
      counts will decrease. To investigate the effects of DE duration on spectral
      counting based quantitative proteomics, we analyzed the same sample via
      multidimensional protein identification technology while enabling different DE
      durations (15, 60, 90, 300, 600 s) or turning DE off. Normalized spectral
      abundance factors (NSAFs) measured for abundant proteins varied little with or
      without DE, while enabling DE lead to higher peptide counts, higher NSAFs, and
      better reproducibility of detection for proteins of relatively lower abundance.
      The optimal DE duration, which generated the maximum number of peptides,
      proteins, and peptides per protein, was observed to be 90 s in our settings. We
      developed a mathematical model for analyzing the effects of DE duration on
      peptide spectral counts. We found that the optimal DE duration depends on the
      average chromatographic peak width at the base of eluting peptides and mass
      spectrometry parameters, leading us to calculate an optimized DE duration of 97.9
      s, in excellent agreement with our observations. In this study, we provide a
      systematic approach for the optimization of spectral counts for improved
      quantitative proteomics analysis.

PMID- 19586017
TI  - Intracavitary ligand distribution in tear lipocalin by site-directed tryptophan
      fluorescence.
AB  - Site-directed tryptophan fluorescence has been successfully used to determine the
      solution structure of tear lipocalin. Here, the technique is extended to measure
      the binding energy landscape. Single Trp mutants of tear lipocalin are bound to
      the native ligand and an analogue tagged with a quencher group to both populate
      and discriminate the excited protein states. Steady-state and time-resolved
      fluorescence quenching data reveal the intracavitary state of the ligand. The
      static components of fluorescence quenching identify the residues where
      nonfluorescence complexes form. An asymmetric distribution of the ligand within
      the cavity reflects the complex energy landscape of the excited protein states.
      These findings suggest that the excited protein states are not unique but consist
      of many substates. The roughness of the binding energy landscape is about 2.5kBT.
      The excited protein states originate primarily from conformational selections of
      loops AB and GH, a portal region. In contrast to static quenching, the dynamic
      components of fluorescence quenching by the ligand are relevant to both local
      side chain and ligand dynamics. Apparent bimolecular rate constants for
      collisional quenching of Trp by the nitroxide moiety are approximately 1 / 5 x
      10(12) M(-1) s(-1). Estimations made for effective ligand concentrations
      establish actual rate constants on the order of 12 x 10(9) M(-1) s(-1). Prior to
      exit from the cavity of the protein, ligands explore binding sites in
      nanoseconds. Although microsecond fluctuations are rate-limiting processes in
      ligand binding for many proteins, accompanying nanosecond motion may be necessary
      for propagation of ligand binding.

PMID- 19586020
TI  - Hyperbranched polymers with a degree of branching of 100% prepared by catalyst
      transfer Suzuki-Miyaura polycondensation.
AB  - Hyperbranched polymers with a degree of branching of 100% were prepared by
      catalyst transfer Suzuki-Miyaura polymerization of AB(2) monomers carrying one
      boronic acid and two aromatic bromo functional groups; in contrast, Suzuki
      Miyaura polymerization of the same AB(2) monomers using a traditional catalyst
      afforded hyperbranched polymers with a branching degree of only approximately
      56%. This is a nice example of controlling the topology of hyperbranched polymers
      via the catalyst.

PMID- 19586019
TI  - Tetranuclear coordination assemblies based on half-sandwich ruthenium(II)
      complexes: noncovalent binding to DNA and cytotoxicity.
AB  - The reaction of [(cymene)RuCl(2)](2) with K(2)Hoxonate (H(3)oxonic = 4,6
      dihydroxy-2-carboxy-1,3,5-triazine acid) in methanol leads to the formation of
      the dinuclear half-sandwich ruthenium(II) complex [(cymene)(2)Ru(2)(mu
      Hoxonato)Cl(2)] (1a). Removal of the chloride ligands of 1a by treatment with
      AgCF(3)SO(3) yields [(cymene)(2)Ru(2)(mu-Hoxonato)(CF(3)SO(3))(2)] (1b), which,
      upon posterior reaction with N,N'-linkers (L = 4,4'-bipyridine (4,4'-bpy), 4,7
      phenantroline (4,7-phen)), gives rise to the formation of the tetranuclear open
      boxes [(cymene)(4)Ru(4)(mu-Hoxonato)(2)(mu-N,N'-L)(2)](CF(3)SO(3))(4) (2a, L =
      4,4'-bpy; 2b, L = 4,7-phen). These systems have been characterized by (1)H NMR,
      UV-vis, and ESI-MS. The single-crystal structures of the dinuclear precursor 1a
      and of the clathrate 2b 4,7-phen have been determined. The interaction of these
      systems with cysteine, mononucleotides, and calf-thymus DNA has been studied by
      means of (1)H NMR, UV-vis, circular dicroism, competitive binding assays, and
      atomic force microscopy imaging. The results show that the robust tetracationic
      ruthenium(II) cyclic systems 2a and 2b do not give ligand exchange reactions
      toward biorelevant ligands. Nevertheless, these systems are able to noncovalently
      bind to DNA, probably at the surface of the major groove, inducing significant
      conformational changes in this biomolecule. It is also interesting to note that
      compounds 2a and 2b, in spite of only giving supramolecular interactions with
      biomolecules, exhibit antitumor activity, particularly toward the human ovarian
      cancer cell line A2780cisR, showing acquired resistance to cisplatin, with
      respective 4.6 and 8.3 microM IC(50) values.

PMID- 19586021
TI  - Band gap control in conjugated oligomers via Lewis acids.
AB  - A simple and effective strategy for optical band gap control is demonstrated
      through the use of a novel small acceptor/donor/acceptor molecule, 1, and group
      13 Lewis acids. Chromophore 1 contains a dithienolesilole donor unit end-capped
      with benzo-2,1,3-thiadiazole (BT) acceptor units. Addition to 1 of
      stoichiometeric quantities of Lewis acids of varying strength resulted in the
      formation of Lewis adducts with progressively red-shifted primary charge-transfer
      absorption bands. These complexes have absorption spectra that approach those of
      known conjugated copolymers containing related units. NMR spectroscopy and X-ray
      diffraction studies revealed that 1 binds 2 equiv of Lewis acid via the nitrogen
      at the 3-position of BT.

PMID- 19586018
TI  - Conformation preference of a flexible cyclohexanetetracarboxylate ligand in three
      new metal-organic frameworks: structures, magnetic and luminescent properties.
AB  - Three novel complexes of formula [Co(5)(OH)(2)(cht)(2)(H(2)O)(10)](n) x 2nH(2)O
      (1) (H(4)cht = cyclohexane-1,2,4,5-tetracarboxylic acid),
      [Zn(2)(cht)(H(2)O)(3)](n) x nH(2)O (2), and [Cd(2)(cht)(H(2)O)(5)](n) x 2nH(2)O
      (3) were synthesized by a hydrothermal reaction of cyclohexane-1,2,4,5
      tetracarboxylic acid in the presence of sodium hydroxide with Co(NO(3))(2) x
      6H(2)O, Zn(NO(3))(2) x 6H(2)O, and Cd(NO(3))(2) x 4H(2)O, respectively. These
      complexes were obtained by controlling the molar ratios of starting materials and
      the pH values of reaction mixtures with an initial pH of 5.87 for 1, 5.50 for 2,
      and 5.57 for 3, respectively. The single-crystal X-ray investigations reveal that
      the cht ligands change their conformations exclusively to the a,e,e,a form in all
      three complexes. Complex 1 features a two-dimensional (2D) metal-organic
      framework (MOF) with an axis surrounded by two zigzag structures, a rectangular
      channel surrounded by two a-carboxylate-metal-a-carboxlate and two e-carboxylate
      metal-e-carboxylate chains, and two smaller distorted square-pyramidal channels
      surrounded by hydroxyl oxygen, cyclohexane, and its two a-carboxylates. Each cht
      ligand connects five cobalt atoms and each cobalt atom is six-coordinated with
      carboxylate-oxygen, hydroxyl, and water molecules. Complex 2 possesses a three
      dimensional (3D) MOF structure that consists of the cht ligands and two types of
      cobalt; one is four-coordinated with carboxylate-oxygens and the other is six
      coordinated with carboxylate-oxygens and water molecules. Each cht ligand is
      bonded to seven zinc atoms. Complex 3 is also a 2D MOF structure constructed by
      seven-coordinated cadmium atoms and the cht ligands. The e-carboxylates of two
      parallel cht ligands are connected to a type of cadmium atoms to form 1D chains,
      and these chains are further connected through a-carboxylates of the ligands and
      another type of cadmium atoms to give the 2D structure. Extensive hydrogen
      bonding interactions involving carboxylate-oxygen atoms and crystallization water
      molecules afford 3D supramolecular networks in complexes 1 and 2. Magnetic
      susceptibility measurement of 1 confirmed a six-coordinated high-spin cobalt(II)
      ion and the presence of magnetic exchange coupling among the three hydroxyl
      oxygen bridged cobalt ions. Fluorescent spectra of complexes 2 and 3 show strong
      fluorescent emissions in the blue region.

PMID- 19586022
TI  - Effect of an in-plane ligand on the electronic structures of bromo-bridged nano
      wire Ni-Pd mixed-metal complexes, [Ni(1-x)Pd(x)(bn)2Br]Br2 (bn = 2S,3S
      diaminobutane).
AB  - Single crystals of quasi-one-dimensional bromo-bridged Ni-Pd mixed-metal
      complexes with 2S,3S-diaminobutane (bn) as an in-plane ligand, [Ni(1
      x)Pd(x)(bn)(2)Br]Br(2), were obtained by using an electrochemical oxidation
      method involving mixed methanol/2-propanol (1:1) solutions containing different
      ratios of [Ni(II)(bn)(2)]Br(2) and [Pd(II)(bn)(2)]Br(2). To investigate the
      competition between the electron-correlation of the Ni(III) states, or Mott
      Hubbard states (MH), and the electron-phonon interaction of the Pd(II)-Pd(IV)
      mixed valence states, or charge-density-wave states (CDW), in the Ni-Pd mixed
      metal compounds, X-ray structure analyses, X-ray oscillation photograph, and
      Raman, IR, ESR, and single-crystal reflectance spectra were analyzed. In
      addition, the local electronic structures of Ni-Pd mixed-metal single crystals
      were directly investigated by using scanning tunneling microscopy (STM) at room
      temperature and ambient pressure. The oxidation states of [Ni(1
      x)Pd(x)(bn)(2)Br]Br(2) changed from a M(II)-M(IV) mixed valence state to a M(III)
      MH state at a critical mixing ratio (x(c)) of approximately 0.8, which is lower
      than that of [Ni(1-x)Pd(x)(chxn)(2)Br]Br(2) (chxn = 1R,2R-diaminocyclohexane)
      (x(c) approximately 0.9) reported previously. The lower value of x(c) for [Ni(1
      x)Pd(x)(bn)(2)Br]Br(2) can be explained by the difference in their CDW
      dimensionalities because the three-dimensional CDW ordering in [Pd(bn)(2)Br]Br(2)
      observed by using X-ray diffuse scattering stabilizes the Pd(II)-Pd(IV) mixed
      valence state more than two-dimensional CDW ordering in [Pd(chxn)(2)Br]Br(2)
      does, which has been reported previously.

PMID- 19586024
TI  - Facile access to the hydrazone functionalized PdGeS cluster [{R(N)Ge(mu-S)3}4Pd6]
      from the thiogermanate anion [{R(N)Ge}2(mu-S)2S2]2-.
AB  - The decanuclear ternary PdGeS cluster [{R(N)Ge(mu-S)(3)}(4)Pd(6)] x MeOH (2 x
      MeOH) has been obtained in high yield by a two-step reaction, involving the
      derivatization of the carbonyl functionalized adamantane-like [(R(1)Ge)(4)(mu
      S)(6)] (R(1) = CMe(2)CH(2)COMe) with N(2)H(4) x H(2)O, and a subsequent reaction
      of the resulting hydrazone functionalized thiogermanate
      (NH(3)NH(2))(2)[(R(N)Ge)(2)(mu-S)(2)S(2)] (R(N) = CMe(2)CH(2)CMeNNH(2), 1) with
      an acidic solution of (N,N'-tmeda)Pd(NO(3))(2). Cluster 2 has an elegant
      molecular structure which can be viewed as an R(N) ligated ensemble of four edge
      sharing [Pd(3)GeS(3)] defect hetercubanes that meet at an unoccupied center.
      Thus, the cluster consists of six square-planar coordinated Pd(II) ions at the
      vertices of a regular octahedron with four faces capped by four [R(N)GeS(3)](3-)
      units. The title compounds were structurally characterized by means of single
      crystal X-ray diffraction as well as physical property measurements. Moreover,
      density functional theory calculations were performed to gain insight into the
      unique coordination situation of the hydrazone substituent.

PMID- 19586023
TI  - Heteronuclear and homonuclear Cu2+ and Zn2+ complexes with multihistidine
      peptides based on zebrafish prion-like protein.
AB  - The homeostasis of metal ions, especially copper and zinc, is a major factor that
      may influence the prion diseases and the biological function of prion protein
      (PrP). The His-rich regions are basic sites for metal binding and antioxidant
      activity of the PrP structures. Animal prion-like proteins contain also His-rich
      domains, and their coordination chemistry may provide better insight into the
      chemistry and biology of PrP structures and related diseases. Herein, we report
      an equilibrium study on heteronuclear Zn(2+)-Cu(2+) complexes with zrel-PrP
      fragments from zebrafish. Potentiometric, spectroscopic, and mass spectrometric
      methods showed that the binding of copper is much more effective than the binding
      of zinc. At physiological pH, both metals bind to the histidine imidazole N
      donors of the studied peptides.

PMID- 19586026
TI  - Characterization of commercial slovenian and cypriot fruit juices using stable
      isotopes.
AB  - The compositions of commercially available fruit juices on the Slovenian and
      Cypriot markets have been compared and checked against the corresponding
      declarations on the packaging. Values of delta(13)C in the pulp, sugars, and
      ethanol (produced by fermentation and distillation) have been obtained by isotope
      ratio mass spectrometry and (D/H)(I) and (D/H)(II) ratios determined by Site
      specific Natural Isotope Fractionation NMR and compared with literature data.
      These data show that some juices on the Slovenian and Cypriot markets were
      adulterated. Measurements of delta(18)O in the water and of (D/H)(II) in the
      ethanol indicated a significant difference in commercially available juices due
      to differences of the "tap" water in Slovenia and Cyprus, as most of the juices
      were diluted from concentrate. Using Principal Component Analysis, very clear
      differentiation can be made between juices from the two countries, arising from
      their distinct aquatic environments and climates. The identification of botanical
      origin of fruit juices was possible only in the case of Slovenian orange and
      apple fruit juices.

PMID- 19586025
TI  - Proton-coupled electron transfer in photosystem II: proton inventory of a redox
      active tyrosine.
AB  - Photosystem II (PSII) catalyzes the light driven oxidation of water and the
      reduction of plastoquinone. PSII is a multisubunit membrane protein; the D1 and
      D2 polypeptides form the heterodimeric core of the PSII complex. Water oxidation
      occurs at a manganese-containing oxygen evolving complex (OEC). PSII contains two
      redox active tyrosines, Y(Z) and Y(D), which form the neutral tyrosyl radicals,
      Y(z)(*) and Y(D)(*). Y(D) has been assigned as tyrosine 160 in the D2 polypeptide
      through isotopic labeling and site-directed mutagenesis. Whereas Y(D) is not
      directly involved in the oxidation of water, it has been implicated in the
      formation and stabilization of the OEC. PSII structures have shown Y(D) to be
      within hydrogen-bonding distance of histidine 189 in the D2 polypeptide.
      Spectroscopic studies have suggested that a proton is transferred between Y(D)
      and histidine 189 when Y(D) is oxidized and reduced. In our previous work, we
      used (2)H(2)O solvent exchange to demonstrate that the mechanism of Y(D) proton
      coupled electron transfer (PCET) differs at high and low pH. In this article, we
      utilize the proton inventory technique to obtain more information concerning PCET
      mechanism at high pH. The hypercurvature of the proton inventory data provides
      evidence for the existence of multiple, proton-donation pathways to Y(D)(*). In
      addition, at least one of these pathways must involve the transfer of more than
      one proton.

PMID- 19586027
TI  - Synthesis and characterization of a structured lipid from amaranth oil as a
      partial fat substitute in milk-based infant formula.
AB  - The aim of this study was to use enzymatic interesterification techniques to
      modify underutilized amaranth oil as a structured lipid (SL) by increasing its
      palmitic acid content at the sn-2 position and incorporating docosahexaenoic acid
      (DHA). This SL can be partially or complementarily used in milk-based infant
      formulas to deliver a lipid component similar to that in breast milk. Amaranth
      oil was modified by enzymatic interesterification in two stages. First, the
      palmitic acid content was increased specifically at the sn-2 position to resemble
      breast milk triacylglycerols (TAGs) using Novozym 435 lipase. Then DHA was
      incorporated, mainly at the sn-1,3 positions using Lipozyme RM IM, a sn-1,3
      specific lipase. An optimization model was developed to determine the exact
      parameter combinations to incorporate a specific amount of DHA (1.0-2.5%). The
      model suggestions were used for a gram-scale interesterification to yield the
      expected product. The final SL composition was as follows: palmitic acid, 33.9%;
      stearic acid, 2.8%; oleic acid, 23.3%; linoleic acid, 37.3%; linolenic acid,
      0.7%; and docosahexaenoic acid, 1.9%. The original amaranth oil and the final SL
      were characterized by determining the fatty acid composition, melting profile,
      chemical characteristics, oxidative stability (peroxide, p-anisidine, and total
      oxidation values), and phytosterol, tocopherol, and squalene contents. The
      physical and chemical characteristics determined in this study support the
      potential application of DHA-containing customized amaranth oil (DCAO) as a
      partial fat substitute or complement for milk-based infant formula. Research on
      the application and stability of this SL used in an infant formula is being
      conducted.

PMID- 19586028
TI  - Protein hydration dynamics and molecular mechanism of coupled water-protein
      fluctuations.
AB  - Protein surface hydration is fundamental to its structural stability and
      flexibility, and water-protein fluctuations are essential to biological function.
      Here, we report a systematic global mapping of water motions in the hydration
      layer around a model protein of apomyoglobin in both native and molten globule
      states. With site-directed mutagenesis, we use intrinsic tryptophan as a local
      optical probe to scan the protein surface one at a time with single-site
      specificity. With femtosecond resolution, we examined 16 mutants in two states
      and observed two types of water-network relaxation with distinct energy and time
      distributions. The first water motion results from the local collective hydrogen
      bond network relaxation and occurs in a few picoseconds. The initial hindered
      motions, observed in bulk water in femtoseconds, are highly suppressed and
      drastically slow down due to structured water-network collectivity in the layer.
      The second water-network relaxation unambiguously results from the lateral
      cooperative rearrangements in the inner hydration shell and occurs in tens to
      hundreds of picoseconds. Significantly, this longtime dynamics is the coupled
      interfacial water-protein motions and is the direct measurement of such
      cooperative fluctuations. These local protein motions, although highly
      constrained, are necessary to assist the longtime water-network relaxation. A
      series of correlations of hydrating water dynamics and coupled fluctuations with
      local protein's chemical and structural properties were observed. These results
      are significant and reveal various water behaviors in the hydration layer with
      wide heterogeneity. We defined a solvation speed and an angular speed to quantify
      the water-network rigidity and local protein flexibility, respectively. We also
      observed that the dynamic hydration layer extends to more than 10 A. Finally,
      from native to molten globule states, the hydration water networks loosen up, and
      the protein locally becomes more flexible with larger global plasticity and
      partial unfolding.

PMID- 19586029
TI  - Determination of parathion in vegetables by electrochemical sensor based on
      molecularly imprinted polyethyleneimine/silica gel films.
AB  - A novel sensor for the determination of parathion based on coupled grafting of
      the functional macromolecule polyethyleneimine on surfaces of silica gel
      particles via a surface imprinting method using molecular imprinting technology
      was fabricated. The electrochemical behavior of parathion at the imprinted sensor
      was characterized by cyclic voltammetry and linear sweeping voltammetry. The
      imprinted films showed high selectivity toward parathion in comparison to similar
      organophosphates. A linear response over parathion concentration in the range of
      0.015-15 mg kg(-1) was exhibited with a detection limit of 0.003 mg kg(-1) (S/N =
      3). The imprinted film sensor has been applied to the determination of parathion
      in spiked vegetable samples and shows promise for fast and selective
      determination of trace levels of parathion in real samples.

PMID- 19586030
TI  - High-strength composite fibers: realizing true potential of carbon nanotubes in
      polymer matrix through continuous reticulate architecture and molecular level
      couplings.
AB  - Carbon nanotubes have unprecedented mechanical properties as defect-free
      nanoscale building blocks, but their potential has not been fully realized in
      composite materials due to weakness at the interfaces. Here we demonstrate that
      through load-transfer-favored three-dimensional architecture and molecular level
      couplings with polymer chains, true potential of CNTs can be realized in
      composites as initially envisioned. Composite fibers with reticulate nanotube
      architectures show order of magnitude improvement in strength compared to
      randomly dispersed short CNT reinforced composites reported before. The molecular
      level couplings between nanotubes and polymer chains results in drastic
      differences in the properties of thermoset and thermoplastic composite fibers,
      which indicate that conventional macroscopic composite theory fails to explain
      the overall hybrid behavior at nanoscale.

PMID- 19586032
TI  - Acid-catalyzed skeletal rearrangement of epoxy alkynes: a fast access to highly
      functionalized allenes.
AB  - The acid-catalyzed reaction of epoxy alkyne involves an epoxide ring-opening
      attacked by pi-alkyne, leading to a semipinacol-type rearrangement. In this
      process, a type of carbon-carbon 3,3-migration of the alkyne system has been
      discovered, which is promoted both by epoxide inducing and hydroxide promoting.
      This transformation enables the fast synthesis of allenes in mild conditions.

PMID- 19586031
TI  - Changes in antioxidant compounds during the shelf life of commercial tomato
      juices in different packaging materials.
AB  - Tomatoes provide an optimal mix of dietary antioxidants that may be responsible
      for the reported health benefits of tomato consumption. However, technological
      processing, packaging materials, and storage conditions have an impact on the
      nutritional quality of tomato products by affecting the stability of antioxidant
      nutrients to different extents. In this study, we evaluated the stability of the
      antioxidant compounds (lycopene, ascorbic acid, total phenols, and total
      flavonoids) present in commercially available tomato juices during storage
      extended for 12 months at three different temperatures (8, 22, and 37 degrees C).
      To further characterize the impact of storage conditions, two commonly used
      packaging materials (Tetra pack and glass bottles) were used to determine whether
      packaging materials affect antioxidant stability. Overall, the total lycopene,
      total phenolic compounds, and total flavonoids remained almost stable during
      storage for 12 months, regardless of the packaging material used, indicating that
      tomato juices maintain their nutritional value in terms of antioxidant
      composition during their shelf life. However, ascorbic acid was the most labile
      antioxidant and was markedly affected by storage conditions. The hydrophilic
      total antioxidant activity (TAA) paralleled the losses in ascorbic acid content,
      whereas the lipophilic TAA remained substantially stable throughout the storage
      trial.

PMID- 19586034
TI  - A new route to acyclic diaminocarbenes via lithium-halogen exchange.
AB  - A lithium-halogen exchange route has been developed to generate acyclic
      diaminocarbenes (ADC) from chloroamidinium salts. Convenient access to various
      ADC complexes (B, Rh, Ir, Pd) stems from a one-pot transmetalation protocol.
      Formation of a carbenoid species is suggested by 1D and 2D NMR studies with a
      (13)C-labeled chloroamidinium precursor and also by X-ray structures of
      transition metal-carbene complexes. Rh-ADC complex 4 is an effective catalyst for
      the 1,2-addition of aryl boronic acids to aryl aldehydes.

PMID- 19586033
TI  - Synthesis and evaluation of 3-aroylindoles as anticancer agents: metabolite
      approach.
AB  - BPR0L075 (2) is a potential anticancer drug candidate designed from
      Combretastatin A-4 (1) based on the bioisosterism principle. Metabolites of 2,
      proposed from in vitro human microsome studies, were synthesized, leading to the
      identification of metabolite-derived analogue 10 with 40-350 pM potency against
      various cancer cell lines. Insights gained from the major inactive metabolite of
      2 led to the development of 29, with better pharmacokinetics and improved potency
      in the tumor xenograft model than 2.

PMID- 19586036
TI  - Identification of novel falcipain-2 inhibitors as potential antimalarial agents
      through structure-based virtual screening.
AB  - The SPECS database was screened against falcipain-2 with two different docking
      methods to identify structurally diverse nonpeptidic inhibitors. Twenty-eight
      nonpeptidic molecules among 81 compounds tested were identified as potential
      inhibitors of falcipain-2. One of the inhibitors exhibited in vitro activity with
      an IC50 value of 2.4 microM. Furthermore, the similarity analysis has
      demonstrated that it is feasible to find novel diverse falcipain-2 inhibitors
      with similar steric shape through virtual screening of large-scale chemical
      libraries.

PMID- 19586037
TI  - Re-evaluating the Gibbs analysis of surface tension at the air/water interface.
AB  - Molecular areas of soluble films at the air/water interface have traditionally
      been calculated by applying the Gibbs equation to the steep linear decline in
      surface tension as the bulk concentration increases. This approach presupposes
      that the interface is saturated in the "Gibbs region," thereby allowing a single
      unique area to be calculated. We show that the areas derived by the Gibbs
      equation (typically 50-60 A(2)/molecule) are much too large to account for the
      abrupt surface tension decline. Moreover, a surface tension/concentration plot
      was observed for a system where micelle formation does not interfere with the
      Gibbs region. Nonetheless, the surface tension plot leveled off, ostensibly owing
      to saturation, when the Gibbs approach predicted a continued linear decline,
      proving that the interface in the Gibbs region is not saturated as generally
      assumed. This conclusion means that the hundreds of published molecular areas
      obtained by the Gibbs approach should be reconsidered.

PMID- 19586039
TI  - Dioxygen activation by mononuclear copper enzymes: insights from a tripodal
      ligand mimicking their Cu(M) coordination sphere.
AB  - A mononuclear cuprous complex is proposed as a novel in silico model for the
      Cu(M) active site of noncoupled copper monooxygenases. To the best of our
      knowledge, it is one of the first biomimicking models that allows one to recover
      the intimate structural features of the enzymatic oxygenated adducts and to gain
      clear-cut insights relevant to dioxygen activation by these enzymes.

PMID- 19586040
TI  - Block copolymer of polyphosphoester and poly(L-lactic acid) modified surface for
      enhancing osteoblast adhesion, proliferation, and function.
AB  - Surface modification is often needed in tissue engineering to enhance the
      interaction between cells and synthetic materials and improve the
      cytocompatibility and cellular functions. In this study, block copolymers of
      poly(L-lactic acid) and poly(ethyl ethylene phosphate) (PLLA-b-PEEP) were
      synthesized and used to modify the PLLA surface via a spin-coating process, to
      understand whether surface modification with polyphosphoester-based polymer will
      be osteoinductive for potential bone tissue engineering applications. X-ray
      photoelectron spectra measurements revealed that phosphorus atomic compositions
      after surface modification increased from 2.09% to 4.39% with increasing PEEP
      length of PLLA-b-PEEP from 58 to 224 units, which also led to a more hydrophilic
      surface property compared with unmodified PLLA. The initial osteoblast attachment
      and proliferation on the modified surfaces were significantly enhanced. Moreover,
      cellular alkaline phosphatase activity and mineral calcium depositions were also
      promoted by PEEP modification. The gene expression determined by reverse
      transcription polymerase chain reaction further revealed that type I collagen and
      osteocalcin expression were upregulated in osteoblasts cultured on the modified
      surfaces, indicating that PEEP modification might be potentially osteoinductive
      and favorable for further application in bone tissue engineering.

PMID- 19586042
TI  - Phosphole-triazole hybrids: a facile synthesis and complexation with Pd(II) and
      Pt(II) salts.
AB  - The copper-promoted Huisgen reaction of alpha-ethynylphosphole P-oxides with aryl
      azides affords alpha-(1-aryl-1,2,3-triazol-4-yl)phospholes in high yield. The
      alpha-(1-phenyl-1,2,3-triazol-4-yl)phosphole exhibits different coordination
      behavior in the complexation with MCl(2)(cod) (M = Pd, Pt). It has been revealed
      that P,N-coordination to PdCl(2) dramatically changes the optical properties of
      the newly constructed phosphole-triazole hybrid pi-system.

PMID- 19586043
TI  - Formation and optical properties of compression-induced nanoscale buckles on
      silver nanowires.
AB  - An intriguing formation of nanoscale buckles is discovered when an array of
      aligned silver nanowires was deposited onto prestrained polydimethylsiloxane
      substrates. The spacing distance between the resulting silver nanoparticles
      corresponds to the buckling wavelength of the silver nanowires. The buckled
      nanowires exhibit unique optical properties, such as interruption of scattered
      polarized photons and emission of photons from subwavelength structure, as well
      as surface-enhanced Raman scattering at the vicinity of the formed nanobuckles.
      In this way, they have great potentials for nano-opto devices, catalysts for
      chemical reactions, and functional materials for chemical detections.

PMID- 19586041
TI  - Glucagon-like peptide-1 functionalized PEG hydrogels promote survival and
      function of encapsulated pancreatic beta-cells.
AB  - Encapsulating pancreatic islets in a semipermeable poly(ethylene glycol) (PEG)
      hydrogel membrane holds potential as an immuno-isolation barrier for the
      treatment of type 1 diabetes mellitus. The semipermeable PEG hydrogel not only
      permits free diffusion of nutrients, metabolic waste, and insulin produced from
      the encapsulated beta-cells, but also provides a size-exclusion effect to prevent
      direct contact of entrapped islets to host immune cells and antibodies. However,
      the use of unmodified PEG hydrogels for islet encapsulation is not ideal, as
      there is no bioactive cue to promote the long-term survival and function of the
      encapsulated cells. Herein, we report the synthesis and characterization of a
      bioactive glucagon-like peptide 1 (GLP-1) analog, namely, GLP-1-cysteine or GLP
      1C, and the fabrication of functional GLP-1 immobilized PEG hydrogels via a
      facile thiol-acrylate photopolymerization. The immobilization of bioactive GLP-1C
      within PEG hydrogels is efficient and does not alter the bulk hydrogel
      properties. Further, the GLP-1 immobilized PEG hydrogels enhance the survival and
      insulin secretion of encapsulated islets. Overall, this study demonstrates a
      strategy to modify PEG hydrogels with bioactive peptide moieties that can
      significantly enhance the efficacy of islet encapsulation.

PMID- 19586044
TI  - Ligand exchange reactions and hydroamination with tris(oxazolinyl)borato yttrium
      compounds.
AB  - Ligand substitution reactions and catalytic hydroamination/cyclization of
      aminoalkenes have been studied with a new oxazolinylborato yttrium compound,
      tris(4,4-dimethyl-2-oxazolinyl)phenylborato bis(trimethylsilylmethyl)yttrium
      ([Y(kappa(3)-To(M))(CH(2)SiMe(3))(2)(THF)], 1). THF exchange in 1 is rapid at
      room temperature, and activation parameters obtained by simulation of (1)H NMR
      spectra acquired from 190 to 280 K are consistent with a dissociative mechanism
      (DeltaS(++) = 30 +/- 1 e.u., DeltaG(++) = 11.9 kcal mol(-1) at 243 K). The
      related phosphine oxide adduct [Y(kappa(3)-To(M))(CH(2)SiMe(3))(2)(OPPh(3))] (2)
      also undergoes exchange via OPPh(3) dissociation with a much higher barrier
      (DeltaG(++) = 15.0 kcal mol(-1) at 320 K). Compound 1 reacts with the amines
      (t)BuNH(2), para-MeC(6)H(4)NH(2), and 2,6-(i)Pr(2)C(6)H(3)NH(2) to provide six
      coordinate [Y(kappa(3)-To(M))(NHR)(2)(THF)] (3: R = (t)Bu; 4: R = para
      MeC(6)H(4)) and five-coordinate [Y(kappa(3)-To(M))(NH-2,6-(i)Pr(2)C(6)H(3))(2)]
      (6). These oxazolinylborato yttrium compounds are precatalysts for the
      cyclization of aminoalkenes; the kinetics of catalytic conversion indicate zero
      order substrate dependence and first-order catalyst dependence. Kinetic
      investigations of ligand exchange processes and hydroamination reactions indicate
      that the tris(oxazolinyl)borato-yttrium interaction is robust even in the
      presence of excess phosphine oxide and primary and secondary amines.

PMID- 19586045
TI  - Dendritic poly(L-lysine)-b-Poly(L-lactide)-b-dendritic poly(L-lysine) amphiphilic
      gene delivery vectors: roles of PLL dendritic generation and enhanced transgene
      efficacies via termini modification.
AB  - As an effort to prepare new efficient gene delivery vectors, we have recently
      developed and reported an amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)
      b-dendritic poly(L-lysine) D(2)-PLLA-D(2) with two-generation PLL dendrons and a
      PLLA block. In this work, we continued to explore the roles of dendritic PLL
      generation in DNA binding and intracellular delivery of gene, and a new series of
      amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L
      lysine)s D(n)-PLLA-D(n) (n = 3-5) were synthesized and were structurally
      characterized. Furthermore, plasmid DNA binding affinity for these cationic
      amphiphiles was examined by agarose gel electrophoresis and fluorescence
      titration assay in pure water and PBS buffer solution containing 150 mM NaCl (pH
      = 7.4), respectively. By dynamic light scattering (DLS) and transmission
      electronic microscopy (TEM), the interaction and complexation in between were
      investigated, concerning the DNA/vector polyplex particle morphologies and zeta
      potentials. Utilizing a human hepatocellular carcinoma cell-line SMMC-7721, cell
      toxicity, and gene transfection in vitro were explored. To further improve
      transgene efficiency for these synthetic cationic amphiphiles as gene delivery
      vectors, new structural DE(n)-PLLA-DE(n) (n = 2-3) were prepared through an amino
      termini modification of the D(n)-PLLA-D(n) (n = 2-3) with less toxic 4,7,10,13
      tetraazatridecanoic acids, and gene transfection with these DE(n)-PLLA-DE(n) (n =
      2-3) was examined with an alternative human gastric carcinoma cell-line HGC-27.
      As a result, the high plasmid DNA binding affinity, low cytotoxicity, and much
      enhanced transgene efficacy suggest a new possible clue to design effective
      synthetic gene delivery vectors with amphiphilic skeleton and less toxic
      polyamine building blocks.

PMID- 19586046
TI  - Macromolecular interaction of halichondrin B analogues eribulin (E7389) and ER
      076349 with tubulin by analytical ultracentrifugation.
AB  - Halichondrin B is an antimitotic drug that inhibits microtubule assembly. To
      understand the molecular details of its interaction with tubulin, we investigated
      the binding of two halichondrin B analogues, eribulin (previously, ER-086526,
      E7389) and ER-076349, to tubulin by quantitative analytical ultracentrifugation.
      Eribulin is currently undergoing phase III clinical trials for cancer; ER-076349
      is a closely related analogue with C.35 hydroxyl instead of C.35 primary amine
      [Towle, M. J., et al. (2001) Cancer Res. 61, 1013]. Below the critical
      concentration for microtubule assembly and in the presence of GDP, tubulin
      undergoes weak self-association into short curved oligomers. Eribulin inhibits
      this oligomer formation 4-6-fold, while ER-076349 slightly stimulates oligomer
      formation by 2-fold. This is in contrast to vinblastine which strongly stimulates
      large spiral polymers by 1000-fold under these same conditions. Vinblastine
      induced spiral formation is strongly inhibited by both eribulin and ER-076349.
      Colchicine binding to the intradimer interface has no significant effect on small
      oligomer formation or the inhibitory activity of eribulin on this process. These
      results suggest that halichondrin B analogues bind to the interdimer interface or
      to the beta-subunit alone, disrupt polymer stability, and compete with
      vinblastine-induced spiral formation. Stathmin is known to form a tight 1:2
      complex with tubulin. Eribulin strongly inhibits formation of the 1:2 stathmin
      tubulin complex (>3.3 kcal/mol), while ER-076349 weakens formation of the 1:2
      complex by approximately 1.9 kcal/mol. These results suggest that eribulin is a
      global inhibitor of tubulin polymer formation, disrupting tubulin-tubulin
      contacts at the interdimer interface. ER-076349 also perturbs tubulin-tubulin
      contacts, but in a more polymer specific manner, reflecting adaptability of the
      interdimer interface to drug and polymer polymorphism. These results suggest
      halichondrin B analogues exhibit unique tubulin-based activities that may
      underlie the clinical utility of these compounds.

PMID- 19586047
TI  - Total synthesis and neuritotrophic activity of farinosone C and derivatives.
AB  - An efficient synthesis of all four possible stereoisomers of the neurotrophic
      amide farinosone C was developed. The absolute and relative configuration was
      assigned by comparison of synthetic material with a derivatized authentic sample
      of the natural product. Several derivatives allowed for the generation of
      preliminary structure activity relationships concerning neurite outgrowth in PC
      12 cells, unravelling L-tyrosinol-amide as the pharmacophore.

PMID- 19586048
TI  - Impact of cardiac troponin T N-terminal deletion and phosphorylation on
      myofilament function.
AB  - Cardiac troponin T (cTnT) is a phosphoprotein that modulates cardiac muscle
      contraction through its extensive and diverse interactions with neighboring thin
      filament proteins. Its N-terminal half is the "glue" that anchors the troponin
      complex to tropomyosin-actin. Until now, studies aimed at investigating the role
      of the N-terminal tail region have not considered the effects of phosphorylation.
      To understand better the regulatory role of the N-terminal tail region of
      phosphorylated cTnT, we investigated the functional effects of N-terminal
      deletion (amino acids 1-91) and phosphorylation on Ca(2+) dependence of
      myofilament isometric force production, isometric ATPase rate, and thin filament
      sliding speed. Chemomechanical profiles were assessed in detergent permeabilized
      fiber preparations where the native troponin (cTn) was exchanged with recombinant
      cTn engineered to contain modified cTnT (truncated, phosphorylated) in the
      presence of wild-type cTnI and cTnC. Removal of the cTnT N-terminal amino acids 1
      91 (cTnT-del) enhances myofilament responsiveness to nonsaturating Ca(2+) levels
      (the physiological range in cardiac myocytes). However, at saturating Ca(2+)
      levels, there is a reduction in isometric tension and ATPase rate. On one hand,
      phosphorylation of cTnT-del attenuates the sensitizing effect induced by
      truncation of the N-terminal tail, "resetting" myofilament Ca(2+) responsiveness
      back to control levels. On the other hand, it impairs isometric tension
      development and ATPase rate. Interestingly, phosphorylation of cTnT (cTnT-P)
      differentially regulates tension cost (an index of cross-bridge cycling rate):
      increased by cTn-del-P and decreased by intact cTn-wt-P. Like the isometric fiber
      data, sliding speed of thin filaments regulated by cTn-del is more sensitive to
      Ca(2+) compared with cTn-wt. Phosphorylation of cTnT (whether cTnT-del or -wt)
      depresses sliding speed and is associated with Ca(2+) desensitization of thin
      filament sliding speed.

PMID- 19586049
TI  - Selective protein adsorption on polymer patterns formed by self-organization and
      soft lithography.
AB  - Thin films, with both isotropic and ordered patterns of polymer domains, are used
      as substrates to study selective adsorption of two proteins (concanavalin A and
      lentil lectin) and to test reconstruction of polymer patterns by these proteins.
      Integral geometry approach is used to compare quantitatively fluorescence
      micrographs of protein patches with AFM images of original isotropic patterns,
      formed during blend casting of polystyrene/poly(methyl methacrylate) and
      PS/poly(ethylene oxide). Preferential adsorption of both lectins to PMMA phase
      domains, enhanced for PS/PMMA interfaces is concluded. In turn, protein binding
      to PS phase regions of PS/PEO blends is highly selective. Ordered protein
      grouping is obtained as a result of selective adsorption to alternating stripes
      of polystyrene (partly brominated to enable identification) and cross-linked PEO,
      prepared with solvent-assisted micromolding applied to PBrS/PEO bilayers.
      Biological activity test, performed with concanavalin A, confirms preserved
      functionality of a complementary protein, carboxypeptidase Y, adsorbed to polymer
      patterns.

PMID- 19586050
TI  - Ring-opening polymerization of 19-electron [2]cobaltocenophanes: a route to high
      molecular-weight, water-soluble polycobaltocenium polyelectrolytes.
AB  - Water-soluble, high-molecular-weight polycobaltocenium polyelectrolytes have been
      prepared by ring-opening polymerization (ROP) techniques. Anionic polymerization
      of a strained 19-electron dicarba[2]cobaltocenophane followed by oxidation in the
      presence of ammonium chloride resulted in the formation of oligomers with up to
      nine repeat units. Thermal ROP of dicarba[2]cobaltocenophane followed by
      oxidation in the presence of ammonium nitrate resulted in the formation of high
      molecular-weight polycobaltocenium nitrate, a redox-active cobalt-containing
      polyelectrolyte.

PMID- 19586051
TI  - Tobacco mosaic virus (TMV) inhibitors from Picrasma quassioides Benn.
AB  - To investigate natural inhibitors against tobacco mosaic virus (TMV) from plants,
      10 known beta-carboline alkaloids and one quassinoid have been isolated from MeOH
      extract of the wood of Picrasma quassioides Benn. These compounds were screened
      for their inhibitory activities against tobacco mosaic virus (TMV). The activity
      of each compound against TMV infection and replication was tested using a half
      leaf assay method, a leaf-disk method, and Western blotting analyses. All of the
      beta-carboline alkaloids showed moderate anti-TMV activities and exhibited
      synergistic effects when combined with the quassinoid nigakilactone B (11). To
      our knowledge, this is the first report on anti-TMV activity of beta-carbolines
      and their synergistic effects against TMV when combined with a quassinoid.

PMID- 19586052
TI  - Malaria-infected mice live until at least day 30 after a new monomeric trioxane
      combined with mefloquine are administered together in a single low oral dose.
AB  - In only five simple steps and 48% overall yield from the natural trioxane
      artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b
      has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b
      combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected
      mice lived until at least day 30 post infection. Of the five mice in this
      surviving group, four (80%) were completely cured (no parasites in their blood)
      and one mouse had 4% blood parasitemia. Importantly, the efficacy of this ACT
      chemotherapy using monomeric trioxane 4b plus mefloquine hydrochloride is
      considerably better than the efficacy under the same conditions using the popular
      trioxane drug artemether plus mefloquine hydrochloride.

PMID- 19586053
TI  - Synthesis and reactivity of [closo-1-CB9H9-1-N2]: functional group
      interconversion at the carbon vertex of the {closo-1-CB9} cluster.
AB  - The dinitrogen derivative [closo-1-CB(9)H(9)-1-N(2)] (1) was prepared from amine
      [closo-1-CB(9)H(9)-1-NH(3)] (2) and reacted with three types of nucleophiles:
      activated arenes (phenolate and aniline), divalent sulfur compounds (Me(2)S and
      Me(2)NCHS), and pyridine, giving products of substitution at C(cage). The
      reaction of 1 with pyridine gave all four isomers 11a-11d, indicating the Gomberg
      Bachmann mechanism, which involves radical anion [closo-1-CB(9)H(9)](-*) (26).
      The radical and also closed-shell electrophilic aromatic substitution mechanisms
      were probed with the aid of DFT and MP2 computational methods and compared to
      those of phenylation of pyridine. Overall, experimental results supported by
      computational analysis suggest two mechanisms for the substitution of the N(2)
      group in 1: (i) thermal heterolytic cleavage of the C(cage)-N bond and the
      formation of electrophilic carbonium ylide [closo-1-CB(9)H(9)] (19) and (ii)
      electron-transfer-induced homolytic cleavage of the C(cage)-N bond and the
      formation of 26. Decomposition of 1 in MeCN is believed to proceed by the
      nonradical mechanism involving formation of the ylide 19 as the rate-determining
      step with experimental activation parameters DeltaH(double dagger) = 38.4 +/- 0.8
      kcal mol(-1) and DeltaS(double dagger) = 44.5 +/- 2.5 cal mol(-1) K(-1). The
      electron-transfer-induced formation of 26 is consistent with the relatively high
      reduction potential of 1 (E(pc) = -0.54 V), which is more cathodic than that of
      PhN(2)(+) by 0.38 V. Transformations of the phenol 8a and the Me(2)NCHS adduct 10
      were demonstrated by O-methylation of the former and hydrolysis of 10 followed by
      S-alkylative cyclization. Direct products and their derivatives were investigated
      by UV-vis spectroscopy and analyzed with the ZINDO computational method.

PMID- 19586054
TI  - A triple-emission fluorescent probe reveals distinctive amyloid fibrillar
      polymorphism of wild-type alpha-synuclein and its familial Parkinson's disease
      mutants.
AB  - Intracytoplasmic neuronal deposits containing amyloid fibrils of the 140-amino
      acid presynaptic protein alpha-synuclein (AS) are the hallmark of Parkinson's
      (PD) disease and related neurodegenerative disorders. Three point mutations
      (A53T, A30P, and E46K) are linked to early onset PD. Compared to the wild-type
      (WT) protein, the mutants aggregate faster in vitro, but their fibrillar products
      are quite similar. Using the extrinsic multiple-emission probe 4'-(diethylamino)
      3-hydroxyflavone (FE), we demonstrate unique and distinct spectroscopic
      signatures for the amyloid fibrils formed by the WT and mutant AS, presumably
      indicative of subtle differences in supramolecular structure. The two well
      separated emission bands of the FE probe originate from a proton transfer
      reaction in the excited state. The ratiometric response constitutes a sensitive,
      tunable reporter of microenvironmental properties such as polarity and hydrogen
      bonding. The very distinctive fluorescence spectra of the FE probe bound to the
      four AS variants reflect different tautomeric equilibria in the excited state and
      the existence of at least two different binding sites in the fibrils for the dye.
      Deconvolution of the two-dimensional excitation-emission spectra leads to
      estimations of different local dielectric constants and extents of hydration
      characteristic of the proteins. The sensitivity of such a simple external probe
      to conformational alterations induced by point mutations is unprecedented and
      provides new insight into key phenomena related to amyloid fibrils: plasticity,
      polymorphism, propagation of structural features, and structure-function
      relationships underlying toxicity.

PMID- 19586058
TI  - DFT analysis of the reaction paths of formaldehyde decomposition on silver.
AB  - Periodic density functional theory is used to study the dehydrogenation of
      formaldehyde (CH(2)O) on the Ag(111) surface and in the presence of adsorbed
      oxygen or hydroxyl species. Thermodynamic and kinetic parameters of elementary
      surface reactions have been determined. The dehydrogenation of CH(2)O on clean
      Ag(111) is thermodynamically and kinetically unfavorable. In particular, the
      activation energy for the first C-H bond scission of adsorbed CH(2)O (25.8 kcal
      mol(-1)) greatly exceeds the desorption energy for molecular CH(2)O (2.5 kcal
      mol(-1)). Surface oxygen promotes the destruction of CH(2)O through the formation
      of CH(2)O(2), which readily decomposes to CHO(2) and then in turn to CO(2) and
      adsorbed hydrogen. Analysis of site selectivity shows that CH(2)O(2), CHO(2), and
      CHO are strongly bound to the surface through the bridge sites, whereas CO and
      CO(2) are weakly adsorbed with no strong preference for a particular surface
      site. Dissociation of CO and CO(2) on the Ag(111) surface is highly activated and
      therefore unfavorable with respect to their molecular desorption.

PMID- 19586055
TI  - Physical interaction between replication protein A (RPA) and MRN: involvement of
      RPA2 phosphorylation and the N-terminus of RPA1.
AB  - Replication protein A (RPA) is a heterotrimeric protein consisting of RPA1, RPA2,
      and RPA3 subunits that binds to single-stranded DNA (ssDNA) with high affinity.
      The response to replication stress requires the recruitment of RPA and the MRE11
      RAD50-NBS1 (MRN) complex. RPA bound to ssDNA stabilizes stalled replication forks
      by recruiting checkpoint proteins involved in fork stabilization. MRN can bind
      DNA structures encountered at stalled or collapsed replication forks, such as
      ssDNA-double-stranded DNA (dsDNA) junctions or breaks, and promote the restart of
      DNA replication. Here, we demonstrate that RPA2 phosphorylation regulates the
      assembly of DNA damage-induced RPA and MRN foci. Using purified proteins, we
      observe a direct interaction between RPA with both NBS1 and MRE11. By utilizing
      RPA bound to ssDNA, we demonstrate that substituting RPA with phosphorylated RPA
      or a phosphomimetic weakens the interaction with the MRN complex. Also, the N
      terminus of RPA1 is a critical component of the RPA-MRN protein-protein
      interaction. Deletion of the N-terminal oligonucleotide-oligosaccharide binding
      fold (OB-fold) of RPA1 abrogates interactions of RPA with MRN and individual
      proteins of the MRN complex. Further identification of residues critical for MRN
      binding in the N-terminus of RPA1 shows that substitution of Arg31 and Arg41 with
      alanines disrupts the RPA-MRN interaction and alters cell cycle progression in
      response to DNA damage. Thus, the N-terminus of RPA1 and phosphorylation of RPA2
      regulate RPA-MRN interactions and are important in the response to DNA damage.

PMID- 19586059
TI  - Reversible dimerization of (+)-myrmicarin 215B.
AB  - Bronsted acid promoted reversible dimerization of myrmicarin 215B leads to
      formation of a new heptacyclic product, isomyrmicarin 430B, that possesses a
      C1,C2-trans,C2,C3-trans-substituted cyclopentane ring. Mechanistic studies
      illustrate that isomyrmicarin 430B arises by isomerization of isomyrmicarin 430A
      via fragmentation to tricyclic azafulvenium ions. Factors influencing the
      structure of heptacyclic isomyrmicarin products and potential relevance of this
      reversible vinyl pyrroloindolizine dimerization to the biosynthesis of complex
      myrmicarins are discussed.

PMID- 19586056
TI  - Regulation of lymphoid tyrosine phosphatase activity: inhibition of the catalytic
      domain by the proximal interdomain.
AB  - The lymphoid tyrosine phosphatase LYP, encoded by the PTPN22 gene, recently
      emerged as a major player and candidate drug target for human autoimmunity. The
      enzyme includes a classical N-terminal protein tyrosine phosphatase catalytic
      domain and a C-terminal PEST-enriched domain, separated by an approximately 300
      amino acid interdomain. Little is known about the regulation of LYP. Herein, by
      analysis of serial truncation mutants of LYP, we show that the phosphatase
      activity is strongly inhibited by protein regions C-terminal to the catalytic
      domain. We mapped the minimal inhibitory region to the proximal portion of the
      interdomain. We show that the activity of LYP is inhibited by an intramolecular
      mechanism, whereby the proximal portion of the interdomain directly interacts
      with the catalytic domain and reduces its activity.

PMID- 19586060
TI  - Novel thermal and microwave-assisted facile route to naphthalen-2(1H)-ones via an
      oxidative alkoxylation-ring-opening protocol.
AB  - Several novel 1,1-disubstituted-8-hydroxynaphthalen-2(1H)-ones have been
      efficiently synthesized via a two-step sequence from 2-hydroxy-1-naphthaldehyde
      oxime. The methodology involves oxidative ring closure and alkoxylation to 3a
      alkoxynaphtho[1,8-de][1,2]oxazin-4(3aH)-ones, followed by thermal ring-opening.
      Both thermal and microwave irradiation conditions were used. A novel one-pot
      reaction of oxime to 8-isopropoxynaphthalene-1,7-diol using microwave irradiation
      is also reported.

PMID- 19586061
TI  - Lobocrasol, a new diterpenoid from the soft coral Lobophytum crassum.
AB  - Lobocrasol (1), possessing an unprecedented diterpenoid skeleton, was isolated
      from the soft coral Lobophytum crassum. The structure of lobocrasol was
      established by extensive analysis of spectroscopic data.

PMID- 19586062
TI  - Structure and formation of the fluorescent compound of Lignum nephriticum.
AB  - The intense blue fluorescence of the infusion of Lignum nephriticum (Eysenhardtia
      polystachya), first observed in the sixteenth century, is due to a novel four
      ring tetrahydromethanobenzofuro[2,3-d]oxacine which is not present in the plant
      but is the end product of an unusual, very efficient iterative spontaneous
      oxidation of at least one of the tree's flavonoids.

PMID- 19586063
TI  - Oxygen-doped nanodiamonds: synthesis and functionalizations.
AB  - Oxadiamondoids representing a new class of carbon nanoparticles were prepared
      from the respective diamondoid ketones via an effective two-step procedure
      involving addition of methyl magnesium iodide and oxidation with
      trifluoroperacetic acid in trifluoroacetic acid. The reactivities of the oxacages
      are determined by the position of the dopant and are in good agreement with
      computational predictions.

PMID- 19586065
TI  - The chiro-optical properties of a lemniscular octaphyrin.
AB  - The match between the calculated TD-DFT electronic circular dichroism spectrum of
      the M,M configuration of the lemniscular [36]octaphyrin 1 and the previously
      reported measured spectrum suggests that the assignment of the latter to the P,P
      enantiomer requires inverting to M,M. The unusually large magnitude of the
      calculated optical rotations for these species may reflect the aromatic character
      of the system.

PMID- 19586064
TI  - Highly regiospecific synthetic approach to monobay-functionalized perylene
      bisimide and di(perylene bisimide).
AB  - Monobay-dichlorinated perylene bisimide and diperylene bisimide have been
      regiospecifically synthesized from tetrachlorinated perylene bisimide in
      different copper-mediated reaction conditions, thus opening a new avenue to their
      monobay-functionalization.

PMID- 19586066
TI  - Concise synthesis of the bryostatin A-ring via consecutive C-C bond forming
      transfer hydrogenations.
AB  - Under the conditions of C-C bond forming transfer hydrogenation, 1,3-propanediol
      1 engages in double asymmetric carbonyl allylation to furnish the C(2)-symmetric
      diol 2. Double ozonolysis of 2 followed by TBS protection delivers aldehyde 3,
      which is subject to catalyst directed carbonyl reverse prenylation via transfer
      hydrogenation to deliver neopentyl alcohol 4 and, ultimately, the bryostatin A
      ring 7. Through use of two consecutive C-C bond forming transfer hydrogenations,
      the Evans' bryostatin A-ring 7 is prepared in less than half the manipulations
      previously reported.

PMID- 19586067
TI  - Elongation of 1,3-polyols via iterative catalyst-directed carbonyl allylation
      from the alcohol oxidation level.
AB  - Iterative enantioselective carbonyl allylation from the alcohol oxidation level
      under the conditions of iridium catalyzed transfer hydrogenation enables chain
      elongation of 1,3-polyols. High levels of catalyst-directed enantioselectivity
      and diastereoselectivity are observed.

PMID- 19586069
TI  - A chemoenzymatic total synthesis of (+)-amabiline.
AB  - The readily available and enzymatically derived cis-1,2-dihydrocatechol 3 has
      been converted, over 15 steps, into (+)-amabiline, the non-natural enantiomeric
      form of a crinine-type alkaloid.

PMID- 19586071
TI  - Time dependent growth of the block copolymer P123 micelles near cloud point:
      employing heat cycling as a tool to form kinetically stable wormlike micelles.
AB  - The sphere-to-rod growth behavior of the triblock copolymer EO(20)PO(70)EO(20)
      (P123) micelles has been studied in an aqueous medium by dynamic light scattering
      (DLS), viscometry, and small angle neutron scattering (SANS) techniques. Unlike
      the other aqueous pluronic systems, the P123 solutions show a time dependent
      sphere-to-rod micellar growth in the aqueous medium on approaching their cloud
      points. The rate of micellar growth increases with increase in temperature, but
      quite interestingly, it improves rather dramatically when the copolymer solutions
      are subjected to heat cycling, i.e., heating them to the phase separation and
      subsequently cooling them back to below their cloud points. The observed
      kinetically restricted micellar growth has been attributed to the slow dynamics
      of the micellar restructuring processes essential to arrive at the temperature
      dependent equilibrium structure. It has been suggested that the improvement in
      the micellar growth rate upon heat cycling is due to overcoming of the activation
      energy associated with the micellar restructuring process. In the presence of
      water-structure-making salts like NaCl, such heat cycling produces kinetically
      stable wormlike micelles at room temperature, which is observed for the first
      time in the aqueous pluronic systems.

PMID- 19586068
TI  - Stereoselective synthesis of cyclic ethers via the palladium-catalyzed
      intramolecular addition of alcohols to phosphono allylic carbonates.
AB  - Cross metathesis of the acrolein-derived phosphono allylic carbonate and hydroxy
      alkenes using second generation Grubbs catalyst and copper(I) iodide gave the
      substituted phosphonates in good yield. Stereospecific palladium(0)-catalyzed
      cyclization gave tetrahydrofuran and tetrahydropyran vinyl phosphonates.
      Regioselective Wacker oxidation of the vinyl phosphonate gave the beta-keto
      phosphonate, which underwent HWE reaction with benzaldehyde to yield the
      unsaturated ketone. The utility of the cross metathesis/cyclization protocol was
      further demonstrated by a formal synthesis of centrolobine.

PMID- 19586072
TI  - Piperidinium, piperazinium and morpholinium ionic liquid crystals.
AB  - Piperidinium, piperazinium and morpholinium cations have been used for the design
      of ionic liquid crystals. These cations were combined with several types of
      anions, namely bromide, tetrafluoroborate, hexafluorophosphate, dodecylsulfate,
      bis(trifluoromethylsulfonyl)imide, dioctylsulfosuccinate,
      dicyclohexylsulfosuccinate, and dihexylsulfosuccinate. For the bromide salts of
      piperidinium containing one alkyl chain, the chain length was varied, ranging
      from 8 to 18 carbon atoms (n = 8, 10, 12, 14, 16, 18). The compounds show a rich
      mesomorphic behavior. High-ordered smectic phases (crystal smectic E and T
      phases), smectic A phases, and hexagonal columnar phases were observed, depending
      on the type of cation and anion. The morpholinium compounds with sulfosuccinate
      anions showed hexagonal columnar phases at room temperature and a structural
      model for the self-assembly of these morpholinium compounds into hexagonal
      columnar phases is proposed.

PMID- 19586073
TI  - Hamiltonian replica exchange method studies of a leucine zipper dimer.
AB  - A melting curve (stability versus temperature) of a leucine zipper dimer was
      obtained with the use of explicit solvent molecular dynamics (MD). Leucine
      zippers form stable dimers in solution at physiological temperatures by formation
      of coiled coil alpha helical structures, using a characteristic heptadic
      repeating unit. We simulated a 31-residue truncation of the 33 residue parallel
      two-stranded leucine zipper (GCN4-p1) of the yeast transcriptional activator GCN4
      that has four such repeats. The dimer remains bound using conventional MD
      sampling at the lowest temperature used, while mainly breaking apart at the
      highest temperature used. However, to obtain a melting curve, the sampling
      efficiency must be improved, especially at the lower temperatures.
      Configurational sampling was enhanced with the introduction of a Hamiltonian
      replica exchange method (HREM), which will be referred to as HTREM, which scales
      the Hamiltonian in both potential and kinetic energies. The potential scaling is
      carried out only for the protein-protein and protein-solvent interactions and the
      kinetic scaling only for the protein degrees of freedom. By limiting the number
      of scaled degrees of freedom, a smaller number of systems can be used relative to
      temperature REM where all degrees of freedom are scaled. The HTREM does enhance
      the sampling especially at the lower temperatures and a melting curve is
      constructed. A mutant leucine zipper is also simulated where five glutamates are
      protonated and five lysines are deprotonated in order to investigate the role
      that electrostatic interactions and salt bridges play in dimer stability. The
      mutant is considerably less stable than the wild type based on the melting
      curves. The connection between dimer stability, monomer alpha helix unwinding,
      and salt bridge presence is investigated. Among the possible salt bridges of GCN4
      p1, those found in experiments are also found in the simulation at the lowest
      simulation temperature, and the corresponding salt bridge fractions at higher
      temperature are much lower. A difference between the N terminal and C terminal
      halves of the monomers regarding their alpha helix stability is found, with the N
      terminal less stable than the C terminal parts, in accord with biophysical
      analyses of two monomeric 16-residue peptides derived from GCN4-p1.

PMID- 19586074
TI  - The future costs, risks and rewards of drug development: the economics of
      pharmacogenomics.
AB  - This article discusses the evolving field of pharmacogenomics, which is the
      science of using genomic markers to predict drug response, and how it may impact
      the future costs, risks and returns to pharmaceutical research and development
      (R&D). We uncover a number of factors and issues that are likely to influence the
      expected returns and, hence, the incentive to invest in new pharmaceutical R&D in
      tandem with the development of pharmacogenomics. Specifically, we identify how
      pharmacogenomics may lower the cost of drug development by shortening drug
      development times. Thus, pharmacogenomics may lead to an increase in a drug's
      effective patent life, and may also increase the demand and adoption rate for new
      products. For these and other reasons, pharmacogenomics may one day enhance
      expected future returns to R&D, leading to higher levels of R&D investment and an
      increased pace of pharmaceutical innovation. Our conclusions must be read with
      much caution, however, as there is considerable uncertainty as to how the area
      will evolve, both clinically and economically. The time horizon necessary for the
      science to develop and be adopted into clinical practice is not clear.
      Nevertheless, we think the issues and factors outlined in this article shed light
      on possible future economic outcomes and changes in the industry's structure,
      conduct and performance. Hopefully, this will provide researchers with avenues to
      pursue regarding a better understanding of the economics of pharmacogenomics.

PMID- 19586076
TI  - Costing infectious disease outbreaks for economic evaluation: a review for
      hepatitis A.
AB  - With the aim to understand and estimate the economic impact of outbreaks of
      community-acquired infections, we performed a review focusing on hepatitis A
      outbreaks, and retained 13 papers that had collected relevant cost information
      during such outbreaks. All costs in this article are expressed in USD, year 2007
      values. The costs of hepatitis A outbreaks ranged from USD140 000 to US36
      million, and the costs per case in an outbreak situation ranged from USD3824 to
      USD200 480. These costs were typically found to be substantially higher than
      estimates from cost-of-illness studies (i.e. costs for sporadic cases) and
      estimates used in cost-effectiveness analyses, mostly because of costly outbreak
      control measures. Post-exposure prophylaxis is a major cost factor, especially
      for food-borne outbreaks. As a result of the increasing proportion of those
      susceptible to hepatitis A in low-incidence countries, future outbreaks could, on
      average, increase in size. The increasing occurrence of hepatitis A cases in
      outbreak situations and the associated control costs should appropriately be
      accounted for in economic evaluations of vaccination programmes in low-incidence
      countries. In order to do this, more studies documenting such outbreak-control
      strategies in terms of costs and resource use are needed.

PMID- 19586075
TI  - The cost and impact of health conditions on presenteeism to employers: a review
      of the literature.
AB  - Employers are becoming concerned with the costs of presenteeism in addition to
      the healthcare and absenteeism costs that have traditionally been explored. But
      what is the true impact of health conditions in terms of on-the-job productivity?
      This article examines the literature to assess the magnitude of presenteeism
      costs relative to total costs of a variety of health conditions. Searches of
      MEDLINE, CINAHL and PubMed were conducted in July 2008, with no starting date
      limitation, using 'presenteeism' or 'work limitations' as keywords. Publications
      on a variety of health conditions were located and included if they assessed the
      total healthcare and productivity cost of one or more health conditions.
      Literature on presenteeism has investigated its link with a large number of
      health conditions ranging from allergies to irritable bowel syndrome. The cost of
      presenteeism relative to the total cost varies by condition. In some cases (such
      as allergies or migraine headaches), the cost of presenteeism is much larger than
      the direct healthcare cost, while in other cases (such as hypertension or
      cancer), healthcare is the larger component. Many more studies have examined the
      impact of pharmaceutical treatment on certain medical conditions and the
      resulting improvement in on-the-job productivity. Based on the research reviewed
      here, health conditions are associated with on-the-job productivity losses and
      presenteeism is a major component of the total employer cost of those conditions,
      although the exact dollar amount cannot be determined at this time.
      Interventions, including the appropriate use of pharmaceutical agents, may be
      helpful in improving the productivity of employees with certain conditions.

PMID- 19586077
TI  - The cost of dementia in Europe: a review of the evidence, and methodological
      considerations.
AB  - Alzheimer's disease (AD) is a leading cause of disability in the elderly, leading
      to a high burden on caregivers and costs to society. This article describes the
      current level of data availability regarding the costs of AD in Europe,
      summarizes and compares findings from previous studies in different countries,
      and discusses the applicability of available data for modelling purposes. A
      literature review was conducted for papers in any language reporting data on
      costs of care for patients with diagnosed dementia or possible/probable AD. Only
      papers reporting patient-level data on costs were included. A total of 16 studies
      were identified: from the Nordic region (4), the UK (3), Spain (3), France (2),
      Italy (2), Belgium (1) and Germany (1). There is large variation in total cost
      estimates, depending on, for example, differences in study methodology, setting,
      type and severity of patients included, range of costs assessed and the choice of
      principle for valuing informal care. The median value for total annual care costs
      in all studies was Euro28 000 (range Euro6614-Euro64 426) [year 2005 values]. Few
      studies assessed aspects of disease severity other than cognitive function. The
      costs of AD in Europe are substantial and increase with disease severity.
      Methodological differences between studies make comparison across countries and
      healthcare systems difficult, and there is a need to standardize methods for
      assessing and valuing informal care. Patient-level information on resource use is
      required to analyse determinants of care costs and predict the impact of
      therapeutic interventions. More data are needed to support future economic
      evaluations of therapies for AD.

PMID- 19586078
TI  - Utility assessment in patients with mental disorders: validity and discriminative
      ability of the time trade-off method.
AB  - BACKGROUND: Preference-based health-state values, also referred to as utility
      scores, are considered an important measure of outcome in the evaluation of
      healthcare. A common approach to elicit utility scores is the use of the time
      trade-off (TTO) method; however, the data on TTO utility scores in patients with
      mental disorders are scarce. OBJECTIVE: To analyse the TTO method in patients
      with mental disorders in terms of discriminative ability, validity and the
      refusal to trade life time (zero trade). METHODS: In patients with affective (n =
      172), schizophrenia spectrum (n = 166) and alcohol-related (n = 160) mental
      disorders, TTO utilities were administered through a standardized interview.
      Measures of quality of life (QOL) EQ-5D, WHOQOL-BREF, subjective (SCL-90R) and
      objective (CGI-S) psychopathology, and functioning (GAF, GARF, SOFAS, HoNOS)
      provided comparison. Discriminative ability was analysed by assessing frequency
      distributions of TTO utilities. Validity was analysed by assessing the
      correlation of TTO utilities with all other scores. The association of a
      patient's QOL, sociodemographic and disease-related variables with zero trade was
      analysed by logistic regression. RESULTS: Of patients with
      affective/schizophrenic/alcohol-related mental disorders, 153/143/145
      (89/86/91%), respectively, completed the TTO elicitation; 29/43/28% of the
      respondents were zero traders. The mean TTO utility was 0.66/0.75/0.61 and the
      median was 0.85/0.95/0.75. TTO utility scores discriminated well among more
      impaired mental health states, but discrimination was limited among less impaired
      health states. In patients with affective and alcohol-related mental disorders,
      TTO utility scores were significantly correlated (mostly moderate: 0.3 < r < 0.5)
      with all other scores. However, in schizophrenic patients, TTO utility scores
      were only a little correlated with other subjective measures and not correlated
      with objective measures. QOL was significantly associated with zero trade; the
      influence of the other variables on zero trade was negligible. CONCLUSIONS: TTO
      utility scores in patients with affective or alcohol-related mental disorders
      were reasonably valid, but discriminative ability was compromised by a ceiling
      effect due to zero trade. In schizophrenic patients, validity of TTO utility
      scores was not demonstrated.

PMID- 19586079
TI  - Outcomes associated with initial versus later vancomycin use in patients with
      complicated skin and skin-structure infections.
AB  - BACKGROUND: Delayed coverage of pathogens including meticillin-resistant
      Staphylococcus aureus (MRSA) in pneumonia and bacteraemia has been associated
      with increased mortality and length of hospital stay (LOS). However, less is
      known about the impact of delayed appropriate coverage in complicated skin and
      skin-structure infections (cSSSIs). OBJECTIVE: To evaluate the clinical and
      economic outcomes associated with early versus late use of vancomycin in the
      management of patients hospitalized for cSSSIs. METHODS: Retrospective analysis
      was performed using an inpatient claims database of >500 US hospitals in 2005.
      Using prescription claims, patients with primary or secondary cSSSI admissions
      were classified into three groups: 1 = early vancomycin monotherapy; 2 = early
      vancomycin combination therapy; 3 = late vancomycin therapy. Outcomes studied
      included LOS and inpatient hospital costs. One-way analysis of variance was used
      for unadjusted analysis and multivariate regression methods were used to control
      for co-variates. RESULTS: A total of 34,942 patients (27.78% of all patients with
      cSSSIs) were treated with vancomycin. Mean age was 54.7 years and 54.3% of the
      patients were males. Mean unadjusted total LOS was 8.46, 9.44 and 13.2 days, and
      hospital costs in 2005 values were USD10 211.94, USD12 361.94 and USD18 344.00
      for groups 1, 2 and 3, respectively. In-hospital mortality rate was highest in
      group 3 (4.18%) and lowest in group 1 (1.75%). Generalized linear models used to
      control for potential confounding variables between early versus late vancomycin
      use suggest that among cSSSI patients late vancomycin use is an independent
      predictor of higher LOS and costs. CONCLUSION: In this large inpatient database,
      later vancomycin use in patients with cSSSIs appears to be significantly
      associated with higher LOS and total costs.

PMID- 19586080
TI  - Pharmaceutical risk-sharing agreements.

PMID- 19586082
TI  - Cost-effectiveness evaluation of a quadrivalent human papillomavirus vaccine in
      Belgium.

PMID- 19586083
TI  - Update of recent reforms in Germany to enhance the quality and efficiency of
      prescribing of proton pump inhibitors and lipid-lowering drugs.

PMID- 19586084
TI  - Long-term care: a test bed for coming reform.

PMID- 19586085
TI  - GERD and Barrett's esophagus: diagnostic and management strategies in the
      geriatric population.
AB  - Chronic gastroesophageal reflux disease (GERD) is a risk factor for the
      development of Barrett's esophagus, the predominant precursor to esophageal
      adenocarcinoma. It is important for the primary care physician to identify those
      at greatest risk of developing Barrett's esophagus for referral for appropriate
      endoscopic screening. Many older patients display atypical symptoms or may be
      asymptomatic. The primary care physician must maintain a high index of suspicion
      and refer anyone who may potentially be at risk of Barrett's esophagus to a
      gastroenterologist. Once a diagnosis of Barrett's esophagus is made, appropriate
      endoscopic surveillance is indicated. For patients who have progressed to
      dysplasia, endoscopic therapy has become the preferred treatment modality because
      of its comparable efficacy to surgical resection with lower morbidity and
      mortality.

PMID- 19586086
TI  - Recognizing and reporting elder abuse and neglect.
AB  - Elder abuse (physical, sexual, or psychological) and neglect (by caretakers or
      self-neglect) are major public health problems. Most cases are not identified by
      clinicians and reported to the appropriate government agencies. There are some
      barriers to clinician identification and reporting of cases of elder abuse or
      neglect. These barriers mainly result from a lack of clinician education and
      comfort regarding this topic. We propose that clinician understanding of the
      phenomenon of elder mistreatment, familiarity with a simple approach to screening
      and identification of cases, awareness of risk factors and warning signs, and
      awareness of appropriate interventions will help to eliminate these barriers and
      result in clinicians properly fulfilling their duty to help protect their most
      vulnerable elderly patients.

PMID- 19586087
TI  - The PCP's role in chronic open-angle glaucoma.
AB  - Chronic open-angle glaucoma is a leading cause of blindness and visual impairment
      in older adults. Optic nerve damage and the associated peripheral and subsequent
      central vision loss are irreversible, but early diagnosis and treatment will give
      patients the best chance to maintain functional vision and quality of life.
      Primary care physicians can assist with the diagnosis of glaucoma by making
      appropriate referrals for routine ophthalmic examinations, especially in patients
      with risk factors for glaucoma. Medication adherence and persistence may also be
      enhanced by discussing strategies to improve medication use and efficacy in the
      primary care setting. Recognition of adverse reactions from glaucoma medications
      and surgeries will allow proper management of these potentially serious
      conditions. Patients with advanced visual deficits can still benefit from
      treatment as well as low-vision and supportive care and should be referred for an
      ophthalmic evaluation. With an understanding of comprehensive glaucoma
      management, primary care physicians play an invaluable role in assisting their
      patients with effective and timely therapy that will result in improved outcomes.

PMID- 19586088
TI  - Eruption on upper extremities.

PMID- 19586089
TI  - Production of O2 Herzberg states in the deep UV photodissociation of ozone.
AB  - High-resolution imaging experiments combined with new electronic structure and
      dynamics calculations strongly indicate that the O((3)P)+O(2) products with very
      low kinetic energy release (E(tr)<0.2 eV) formed in the deep UV (226 nm)
      photodissociation of ozone reflect excitation of the Herzberg states of O(2):
      A(')(3)Delta(u)(v=0,1,2) and A (3)Sigma(u)(+)(v=0,1). This interpretation
      contradicts the earlier assignment to very high (v> or =26) vibrational states of
      O(2)((3)Sigma(g)(-)).

PMID- 19586091
TI  - Energy decomposition analysis of covalent bonds and intermolecular interactions.
AB  - An energy decomposition analysis method is implemented for the analysis of both
      covalent bonds and intermolecular interactions on the basis of single-determinant
      Hartree-Fock (HF) (restricted closed shell HF, restricted open shell HF, and
      unrestricted open shell HF) wavefunctions and their density functional theory
      analogs. For HF methods, the total interaction energy from a supermolecule
      calculation is decomposed into electrostatic, exchange, repulsion, and
      polarization terms. Dispersion energy is obtained from second-order Moller
      Plesset perturbation theory and coupled-cluster methods such as CCSD and CCSD(T).
      Similar to the HF methods, Kohn-Sham density functional interaction energy is
      decomposed into electrostatic, exchange, repulsion, polarization, and dispersion
      terms. Tests on various systems show that this algorithm is simple and robust.
      Insights are provided by the energy decomposition analysis into H(2), methane C
      H, and ethane C-C covalent bond formation, CH(3)CH(3) internal rotation barrier,
      water, ammonia, ammonium, and hydrogen fluoride hydrogen bonding, van der Waals
      interaction, DNA base pair formation, BH(3)NH(3) and BH(3)CO coordinate bond
      formation, Cu-ligand interactions, as well as LiF, LiCl, NaF, and NaCl ionic
      interactions.

PMID- 19586092
TI  - Vertical electronic excitation with a dielectric continuum model of solvation
      including volume polarization. I. Theory.
AB  - A dielectric continuum model of solvation is developed for use in conjunction
      with electronic structure calculation on vertical electronic excitation of a
      solute. Particular attention is paid to volume polarization arising from quantum
      mechanical penetration of solute charge density outside the cavity that nominally
      encloses it, which affects both the fast and slow components of the dielectric
      response. An approximation that closely simulates volume polarization while being
      easier to implement in practice is also described. These approaches are compared
      to other related formulations found in the literature.

PMID- 19586093
TI  - Vertical electronic excitation with a dielectric continuum model of solvation
      including volume polarization. II. Implementation and applications.
AB  - A practical implementation is described for calculation of solute vertical
      electronic excitation with a new dielectric continuum model of solvation.
      Particular attention is given to the specific aspects associated with quantum
      mechanical treatment of the solute, which leads to volume polarization effects
      arising from penetration of the solute charge density outside the cavity
      nominally enclosing it. Some representative computations are presented using this
      method and several other related methods from the literature for the lowest
      vertical transitions of an acetone and a water molecule in dielectric continuum
      models of aqueous solution. These illustrate the two possible extreme behaviors
      wherein the acetone transition is found to be little affected by volume
      polarization, while the water transition is found to be quite sensitive to volume
      polarization, the latter so much so that approximate treatments of volume
      polarization are inadequate.

PMID- 19586090
TI  - Density functional theory based screening of ternary alkali-transition metal
      borohydrides: a computational material design project.
AB  - We present a computational screening study of ternary metal borohydrides for
      reversible hydrogen storage based on density functional theory. We investigate
      the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na,
      or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2))
      plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of
      model structures with trigonal, tetrahedral, octahedral, and free coordination of
      the metal borohydride complexes. Of the over 700 investigated structures, about
      20 were predicted to form potentially stable alloys with promising decomposition
      energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and
      (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by
      selected M(1)(Nb/Rh)(BH(4))(4) alloys.

PMID- 19586094
TI  - Kinetic theory of correlated fluids: from dynamic density functional to Lattice
      Boltzmann methods.
AB  - Using methods of kinetic theory and liquid state theory we propose a description
      of the nonequilibrium behavior of molecular fluids, which takes into account
      their microscopic structure and thermodynamic properties. The present work
      represents an alternative to the recent dynamic density functional theory, which
      can only deal with colloidal fluids and is not apt to describe the hydrodynamic
      behavior of a molecular fluid. The method is based on a suitable modification of
      the Boltzmann transport equation for the phase space distribution and provides a
      detailed description of the local structure of the fluid and its transport
      coefficients. Finally, we propose a practical scheme to solve numerically and
      efficiently the resulting kinetic equation by employing a discretization
      procedure analogous to the one used in the Lattice Boltzmann method.

PMID- 19586095
TI  - Magnetic linear response properties calculations with the Gaussian and augmented
      plane-wave method.
AB  - We introduce a method for the all-electron calculation of the NMR chemical shifts
      and the EPR g tensor using the Gaussian and augmented-plane-wave method. The
      presented approach is based on the generalized density functional perturbation
      theory. The method is validated by comparison with other theoretical methods for
      a selection of small molecules. We also present two exemplary applications that
      involve the calculation of the chemical shifts of a hydrated adenine and the g
      tensor for the E(1)(') center in alpha-quartz using a quantum
      mechanical/molecular mechanical approach.

PMID- 19586096
TI  - Molecular dissociation of hydrogen peroxide (HOOH) on a neural network ab initio
      potential surface with a new configuration sampling method involving gradient
      fitting.
AB  - The O-O bond dissociation of HOOH is investigated on an analytic ab initio
      potential-energy surface obtained by fitting the energies of 25,608
      configurations using neural network (NN) methods. The electronic structure
      calculations are executed using MP2 calculations with the 6-31G* basis set. A new
      data-sampling technique is introduced to collect HOOH configurations in the six
      dimensional hyperspace. This method is based on a comparison of the NN-computed
      gradients at configuration points currently in the database with the target
      gradients. By requiring that the NN gradients closely fit the MP2 target
      gradients, both the potential and the gradients are more accurately fitted. The
      selection criteria also ensure a more uniform distribution of configuration
      points throughout the important regions of configuration space. Molecular
      dynamics (MD) trajectories are not involved in the sampling. The final NN fitting
      yields average absolute and root-mean-squared testing set errors of 0.0060 eV
      (0.58 kJ mol(-1)) and 0.0099 eV (0.96 kJ mol(-1)), respectively. The
      effectiveness of the support vector machine (SVM) method in fitting large ab
      initio databases for MD calculations is investigated by using this method to fit
      the same HOOH database. The SVM fitting quality is tested by comparison to the NN
      fit. It is found that the average absolute and root-mean-squared testing set
      errors for the SVM fit are significantly larger than those obtained using NN
      methods. The total number of parameters in the SVM fit is more than a factor of
      11 times the number of parameters in the NN fit. The trajectory computation time
      using a single NN averages about 1.8 s per picosecond of trajectory time. This
      increases to 9.0 s per picosecond of trajectory time if a five-NN committee is
      employed. The corresponding SVM computational time is almost 24 s per picosecond
      of trajectory time. Consequently, we conclude that a SVM is not as effective in
      fitting large databases for MD calculations as previously proposed methods, and
      thus is not employed to conduct MD studies. We employ the five-member NN
      committee to perform MD calculations at five different internal energies from 3.4
      to 4.2 eV, including zero point energy. The rate coefficients are obtained
      directly from the first-order decay plots. They vary from 0.117 to 0.324 ps(-1).
      A Rice-Ramsperger-Kassel plot is found to exhibit good linearity.

PMID- 19586097
TI  - Modeling of high-order many-mode terms in the expansion of multidimensional
      potential energy surfaces: application to vibrational spectra.
AB  - High-order many-mode terms in the expansion of multidimensional potential energy
      surfaces were modeled by a fully automated molecule-specific fitting of
      parameters within semiempirical molecular orbital theory to low-order grid
      representations of high-level ab initio potentials. Analytical derivatives of the
      total energy with respect to the fitting parameters in combination with global
      and local optimization procedures allow for an efficient and accurate estimation
      of such terms. The accuracy of this approach was tested on the basis of
      vibrational SCF and configuration interaction calculations for the fundamental
      modes of a set of test molecules. Deviations with respect to reference
      calculations were found to be very small. Speedups in computation time by about
      three orders of magnitude relative to conventional calculations were achieved.

PMID- 19586098
TI  - Free-time and fixed end-point optimal control theory in dissipative media:
      application to entanglement generation and maintenance.
AB  - We develop monotonically convergent free-time and fixed end-point optimal control
      theory (OCT) in the density-matrix representation to deal with quantum systems
      showing dissipation. Our theory is more general and flexible for tailoring
      optimal laser pulses in order to control quantum dynamics with dissipation than
      the conventional fixed-time and fixed end-point OCT in that the optimal temporal
      duration of laser pulses can also be optimized exactly. To show the usefulness of
      our theory, it is applied to the generation and maintenance of the vibrational
      entanglement of carbon monoxide adsorbed on the copper (100) surface, CO/Cu(100).
      We demonstrate the numerical results and clarify how to combat vibrational
      decoherence as much as possible by the tailored shapes of the optimal laser
      pulses. It is expected that our theory will be general enough to be applied to a
      variety of dissipative quantum dynamics systems because the decoherence is one of
      the quantum phenomena sensitive to the temporal duration of the quantum dynamics.

PMID- 19586099
TI  - Near-infrared photoabsorption by C60 dianions in a storage ring.
AB  - We present a detailed study of the electronic structure and the stability of
      C(60) dianions in the gas phase. Monoanions were extracted from a plasma source
      and converted to dianions by electron transfer in a Na vapor cell. The dianions
      were then stored in an electrostatic ring, and their near-infrared absorption
      spectrum was measured by observation of laser induced electron detachment. From
      the time dependence of the detachment after photon absorption, we conclude that
      the reaction has contributions from both direct electron tunneling to the
      continuum and vibrationally assisted tunneling after internal conversion. This
      implies that the height of the Coulomb barrier confining the attached electrons
      is at least approximately 1.5 eV. For C(60)(2-) ions in solution electron spin
      resonance measurements have indicated a singlet ground state, and from the
      similarity of the absorption spectra we conclude that also the ground state of
      isolated C(60)(2-) ions is singlet. The observed spectrum corresponds to an
      electronic transition from a t(1u) lowest unoccupied molecular orbital (LUMO) of
      C(60) to the t(1g) LUMO+1 level. The electronic levels of the dianion are split
      due to Jahn-Teller coupling to quadrupole deformations of the molecule, and a
      main absorption band at 10,723 cm(-1) corresponds to a transition between the
      Jahn-Teller ground states. Also transitions from pseudorotational states with 200
      cm(-1) and (probably) 420 cm(-1) excitation are observed. We argue that a very
      broad absorption band from about 11,500 cm(-1) to 13,500 cm(-1) consists of
      transitions to so-called cone states, which are Jahn-Teller states on a higher
      potential-energy surface, stabilized by a pseudorotational angular momentum
      barrier. A previously observed, high-lying absorption band for C(60)(-) may also
      be a transition to a cone state.

PMID- 19586100
TI  - Large-scale correlated study of excited state absorptions in naphthalene and
      anthracene.
AB  - In this paper, we report theoretical calculations of the photoinduced absorption
      (PA) spectrum of naphthalene and anthracene, with the aim of understanding those
      excited states, which are invisible in the linear optical absorption. The excited
      state absorption spectra are computed from the 1B(2u)(+) and the 1B(3u)(+) states
      and a detailed analysis of the many-body character of the states contributing to
      various peaks in the spectra is presented. The calculations are performed using
      the Pariser-Parr-Pople (PPP) Hamiltonian, along with the full configuration
      interaction technique. The role of Coulomb parameters used in the PPP Hamiltonian
      is examined by considering standard Ohno parameters, as well as a screened set of
      parameters. The results of our calculations are extensively compared with the
      experimental data where available and very good agreement has been obtained.
      Moreover, our calculations predict the presence of high intensity features which,
      to the best of our knowledge, have not been explored earlier. We also present
      concrete predictions on the polarization properties of the PA spectrum, which can
      be verified in experiments performed on oriented samples.

PMID- 19586101
TI  - Calculation of the transport and relaxation properties of dilute water vapor.
AB  - Transport properties of dilute water vapor have been calculated in the rigid
      rotor approximation using four different potential energy hypersurfaces and the
      classical-trajectory method. Results are reported for shear viscosity, self
      diffusion, thermal conductivity, and volume viscosity in the dilute-gas limit for
      the temperature range of 250-2500 K. Of these four surfaces the CC-pol surface of
      Bukowski et al. [J. Chem. Phys. 128, 094314 (2008)] is in best accord with the
      available measurements. Very good agreement is found with the most accurate
      results for viscosity in the whole temperature range of the experiments. For
      thermal conductivity the deviations of the calculated values from the
      experimental data increase systematically with increasing temperature to around
      5% at 1100 K. For both self-diffusion and volume viscosity, the much more limited
      number of available measurements are generally consistent with the calculated
      values, apart from the lower temperature isotopically labeled diffusion
      measurements.

PMID- 19586102
TI  - Single-photon and resonance-enhanced multiphoton threshold ionization of the
      allyl radical.
AB  - Pulsed-field-ionization zero-kinetic-energy photoelectron spectra of jet-cooled
      allyl radical (C(3)H(5)) have been recorded following single-photon and resonant
      multiphoton excitation. Simulations based on an orbital ionization model and
      rovibronic photoionization selection rules reliably describe the observed
      intensity distributions in the photoelectron spectra obtained from single-photon
      excitation from the ground state and resonant multiphoton excitation via the 3s
      and the 3p Rydberg states. More than 30 transitions to vibrational levels of the
      cation were identified and assigned on the basis of predictions from ab initio
      calculations.

PMID- 19586103
TI  - A five-dimensional potential-energy surface for the rotational excitation of SO2
      by H2 at low temperatures.
AB  - The SO(2) molecule is detected in a large variety of astronomical objects,
      notably molecular clouds and star-forming regions. An accurate modeling of the
      observations needs a very good knowledge of the collisional excitation rates with
      H(2) because of competition between collisional and radiative processes that
      excite and quench the different rotational levels of SO(2). We report here a five
      dimensional, rigid-body, interaction potential for SO(2)-H(2). As a first
      application, we present rate constants for excitation/de-excitation of the 31
      first levels of SO(2) by para-H(2) at low temperatures. Propensity rules are
      discussed.

PMID- 19586104
TI  - High frequency dynamics in liquid Cs at high pressure.
AB  - We report on an inelastic x-ray scattering investigation of the high frequency
      dynamics of liquid cesium at 493 K and 1 GPa, which corresponds to a density 23%
      higher than that at the room pressure melting point. The analysis of the spectra,
      performed within the framework of the memory function approach suggests the
      existence of two different relaxation processes, i.e., the structural relaxation
      and a second faster one. The dynamical properties thus obtained are compared to
      those reported in the literature for room pressure conditions in order to
      investigate their dependence on pressure. The increase in density is found to
      largely affect the structural relaxation process, though leaving the acoustic
      damping almost unperturbed.

PMID- 19586105
TI  - A new proposed approach to estimate the thermodiffusion coefficients for linear
      chain hydrocarbon binary mixtures.
AB  - Thermodiffusion behaviors in nonassociating mixtures have an important role in
      separation processes of the oil industry. The variations of composition and
      temperature may either lessen or enhance the separation in mixtures. A new model
      regarding the prediction of thermodiffusion coefficients for linear chain
      hydrocarbon binary mixtures using the thermodynamics of irreversible process is
      proposed. The model predicts the net amount of heat transported based on
      available volume for each molecule. This newly proposed model combined with the
      perturbed chain statistical associating fluid theory equation of state has been
      applied to predict thermodiffusion coefficients for binary hydrocarbon mixtures
      of C(10)-nC(i) (i=5,6,7,15,16,17,18), C(12)-nC(i) (i=5,6,7,8,9), and C(18)-nC(i)
      (i=5,6,7,8,9,12). Comparisons of the calculated theoretical results with the
      experimental data show good performance of the proposed model. In particular,
      this model which is based on the kinetic approaches has been found to be the most
      reliable and represents a significant improvement over the earlier models.

PMID- 19586106
TI  - A rigorous foundation of the diffusion-influenced bimolecular reaction kinetics.
AB  - We formulate a general theory of the diffusion-influenced kinetics of
      irreversible bimolecular reactions occurring in the low concentration limit.
      Starting from the classical Liouville equation for the reactants and explicit
      solvent molecules, a formally exact expression for the bimolecular reaction rate
      coefficient is derived; the structures of reactant molecules and the sink
      functions may be arbitrarily complicated. The present theoretical formulation
      shows clearly how the well-known Noyes and Wilemski-Fixman rate theories are
      related and can be improved in a systematic manner. The general properties of the
      rate coefficient such as the long-time behavior and the upper and the lower
      bounds are analyzed. When the reaction can occur at a range of distance, the non
      Markovianity of repeated encounter events between a reactant pair becomes
      significant and either the Noyes theory or the Wilemski-Fixman theory fails. The
      present theory provides a practical method for calculating the rate expression
      for such reactions, which improves significantly on the Wilemski-Fixman theory.

PMID- 19586107
TI  - Reversible gels of patchy particles: role of the valence.
AB  - We simulate a binary mixture of colloidal patchy particles with two and three
      patches, respectively, for several relative concentrations and hence relative
      average valences. For these limited-valence systems, it is possible to reach low
      temperatures, where the lifetime of the patch-patch interactions becomes longer
      than the observation time without encountering phase separation in a colloid-poor
      (gas) and a colloid rich (liquid) phase. The resulting arrested state is a fully
      connected long-lived network where particles with three patches provide the
      branching points connecting chains of two-patch particles. We investigate the
      effect of the valence on the structural and dynamic properties of the resulting
      gel and attempt to provide a theoretical description of the formation and of the
      resulting gel structure based on a combination of the Wertheim theory for
      associated liquids and the Flory-Stockmayer approach for modeling chemical
      gelation.

PMID- 19586108
TI  - Phase transitions and crossovers in reaction-diffusion models with catalyst
      deactivation.
AB  - The activity of catalytic materials is reduced during operation by several
      mechanisms, one of them being poisoning of catalytic sites by chemisorbed
      impurities or products. Here we study the effects of poisoning in two reaction
      diffusion models in one-dimensional lattices with randomly distributed catalytic
      sites. Unimolecular and bimolecular single-species reactions are considered,
      without reactant input during the operation. The models show transitions between
      a phase with continuous decay of reactant concentration and a phase with
      asymptotic nonzero reactant concentration and complete poisoning of the catalyst.
      The transition boundary depends on the initial reactant and catalyst
      concentrations and on the poisoning probability. The critical system behaves as
      in the two-species annihilation reaction, with reactant concentration decaying as
      t(-1/4) and the catalytic sites playing the role of the second species. In the
      unimolecular reaction, a significant crossover to the asymptotic scaling is
      observed even when one of those parameters is 10% far from criticality.
      Consequently, an effective power-law decay of concentration may persist up to
      long times and lead to an apparent change in the reaction kinetics. In the
      bimolecular single-species reaction, the critical scaling is followed by a two
      dimensional rapid decay, thus two crossovers are found.

PMID- 19586110
TI  - Molecular dynamics investigation of hydration of nanoscopic hydrophobic paraffin
      like plates.
AB  - The effect of surface characteristics on the hydration behavior of various
      paraffin-like plates has been investigated. Structure and orientation
      characteristics of the water molecules in the solvation shells of various
      nanoscopic paraffin-like plates differing from each other in the intermolecular
      spacing have been extensively studied using molecular dynamics simulation in
      isothermal-isobaric ensemble. Single particle density distribution of water
      molecules around the plate reveals well defined solvation shells around each of
      the paraffin-like plates studied here. A sharp first peak in the density profile
      in each of the plates signifies no visible dewetting around the paraffin plate.
      Instantaneous density of water molecules around the plate also reveals that the
      plate is sufficiently hydrated and there is no intermittent fluctuation in water
      density in the first hydration shell leading to short lived dewetted state for
      any of the model plates within the two nanosecond time span. This is in contrast
      to the hydration behavior of the intersolute region, where intersolute dewetting
      has been observed for some of the model plates. Thus the present results
      demonstrate that dewetting in the intersolute region of nanoscopic hydrophobic
      plates does not stem from drying interface of the individual solute. No
      significant effect of surface topology on the orientational structure of water
      molecules as revealed through distributions of dipole moment as well as oxygen
      hydrogen bond vectors of a water molecule in different solvation shells has been
      observed.

PMID- 19586109
TI  - Infrared absorption of MgO at high pressures and temperatures: a molecular
      dynamic study.
AB  - We calculate by molecular dynamics the optical functions of MgO in the far
      infrared region 100-1000 cm(-1), for pressures up to 40 GPa and temperatures up
      to 4000 K. An ab initio parametrized many-body force field is used to generate
      the trajectories. Infrared spectra are obtained from the time correlation of the
      polarization, and from Kramers-Kronig relations. The calculated spectra agree
      well with experimental data at ambient pressure. We find that the infrared
      absorption of MgO at CO(2) laser frequencies increases substantially with both
      pressure and temperature and we argue that this may explain the underestimation,
      with respect to theoretical calculations, of the high-pressure melting
      temperature of MgO determined in CO(2) laser-heated diamond-anvil cell
      experiments.

PMID- 19586112
TI  - Influence of CO in the structural and electrical properties of Pt nanocontacts:
      comparison with H2 molecule addition.
AB  - Density-functional theory is used to determine the atomic structure and the zero
      bias conductance of Pt nanocontacts upon CO addition. Three stable atomic
      configurations of the nanocontacts, in conjunction with a statistical analysis of
      their electrical response, are enough to explain the main features of the
      experimental conductance histograms. Remarkably, the role of nonlocal effects
      when approaching the exchange-correlation potential within density-functional
      theory turns out to be crucial for CO molecular-based systems. Finally, a
      comparison with H(2) molecule addition on Pt nanocontacts is presented.

PMID- 19586111
TI  - Nonlinear nanopolaritonics: finite-difference time-domain Maxwell-Schrodinger
      simulation of molecule-assisted plasmon transfer.
AB  - The effect of nonlinear excitations of a nearby two-state dipolar molecule on
      plasmon transfer across a pair of spherical gold nanoparticles is studied
      numerically using a split field finite-difference time-domain Maxwell-Schrodinger
      approach [K. Lopata and D. Neuhauser, J. Chem. Phys. 130, 104707 (2009)]. It is
      observed in the linear response regime that the molecule has a drastic effect on
      plasmon transfer; specifically, there is a Fano-type resonance that serves to
      scatter localized plasmons from x-polarization to y-polarization. With increasing
      nonlinearity of the molecular excitation, the scattering effect saturates due to
      the limited capacity of the molecule to absorb and radiate energy once the
      excited and ground states are equally populated.

PMID- 19586113
TI  - Transition from dynamic to static disorder in one-dimensional organic
      semiconductors.
AB  - A generic model Hamiltonian is proposed for the study of the transport in a quasi
      one-dimensional semiconductor in the charge transport regime intermediate between
      dynamic localization and static localization due to structural disorder. This
      intermediate regime may be appropriate for many organic semiconductors, including
      polymers, discotic liquid crystals, and DNA. The dynamics of the charge carrier
      is coupled to classical Langevin oscillators whose spectral density can be
      adjusted to model experimental systems of interest. In the proposed model, the
      density of states is constant (at constant temperature) and the transition from
      dynamic to static disorder is controlled by a single parameter. This paper
      further clarifies that the density of states may not contain all the information
      needed to describe the charge transport in some materials.

PMID- 19586115
TI  - Computational study of nanometer-scale self-propulsion enabled by asymmetric
      chemical catalysis.
AB  - We present a detailed analysis of the self-propulsion of a model nanometer-scale
      motor by reactive molecular dynamics simulations. The nanomotor is decorated with
      catalysts on only one side that promotes exothermic reactions of the surrounding
      fuel. Unidirectional drift of the nanomotor is observed that is superimposed on
      its Brownian motion. The motor response upon the application of external loads is
      also investigated and the thermodynamic efficiency is calculated. It is shown
      that the propulsion of our nanomotor can be understood by a momentum transfer
      model which is akin to rocket propulsion.

PMID- 19586114
TI  - Water dynamics in large and small reverse micelles: from two ensembles to
      collective behavior.
AB  - The dynamics of water in Aerosol-OT reverse micelles are investigated with
      ultrafast infrared spectroscopy of the hydroxyl stretch. In large reverse
      micelles, the dynamics of water are separable into two ensembles: slow
      interfacial water and bulklike core water. As the reverse micelle size decreases,
      the slowing effect of the interface and the collective nature of water
      reorientation begin to slow the dynamics of the core water molecules. In the
      smallest reverse micelles, these effects dominate and all water molecules have
      the same long time reorientational dynamics. To understand and characterize the
      transition in the water dynamics from two ensembles to collective reorientation,
      polarization and frequency selective infrared pump-probe experiments are
      conducted on the complete range of reverse micelle sizes from a diameter of 1.6
      20 nm. The crossover between two ensemble and collective reorientation occurs
      near a reverse micelle diameter of 4 nm. Below this size, the small number of
      confined water molecules and structural changes in the reverse micelle interface
      leads to homogeneous long time reorientation.

PMID- 19586116
TI  - Theoretical investigation of the divacancies in boron nitride nanotubes:
      properties and surface reactivity toward various adsorbates.
AB  - The recent study has shown that the point defects formed under electron
      irradiation in the boron nitride nanotubes (BNNTs) are primarily BN divacancies.
      In the present work, we explore the properties of BNNTs with divacancies and
      estimate their surface reactivity toward various adsorbates through density
      functional theory calculations. Divacancies in BNNTs can self-heal by
      spontaneously reconstructing stable structures that have two pentagons side by
      side with an octagon (585). The formation energies, which strongly depend on the
      divacancy orientation with respect to the tube axis, increase with increasing
      tube diameters. Compared to the reactivity of the perfect BNNT, those sites near
      the divacancies have a higher reactivity due to the formation of frustrated B-B
      and N-N bonds and the local strain induced by pentagonal and octagonal rings. The
      present results might be useful for deeply understanding the nature of defects in
      BNNTs and rendering BNNTs promising for many applications, especially in
      nanoelectronics.

PMID- 19586117
TI  - Chiral electron transport: scattering through helical potentials.
AB  - We present a model for the transmission of spin-polarized electrons through
      oriented chiral molecules, where the chiral structure is represented by a helix.
      The scattering potential contains a confining term and a spin-orbit contribution
      that is responsible for the spin-dependent scattering of electrons by the
      molecular target. The differential scattering cross section is calculated for
      right- and left-handed helices and for arbitrary electron spin polarizations. We
      apply our model to explain chiral effects in the intensity of photoemitted
      polarized electrons transmitted through thin organic layers. These are molecular
      interfaces that exhibit spin-selective scattering with surprisingly large
      asymmetry factors as well as a number of remarkable magnetic properties. In our
      model, differences in intensity are generated by the preferential transmission of
      electron beams whose polarization is oriented in the same direction as the sense
      of advance of the helix. This model can be easily extended to the Landauer regime
      of conductance where conductance is due to elastic scattering, so that we can
      consider the conductance of chiral molecular junctions.

PMID- 19586118
TI  - The dependence of the electrochemical properties of perfluorosulfonic acid
      membrane/water systems on repeat unit structure.
AB  - We developed a molecular thermodynamic framework to describe the dependence of
      the electrochemical properties of a perfluorosulfonic acid (PFSA) membrane/water
      system on the polymer structure. To better understand the behavior of the polymer
      membrane/water system, we developed a lattice model based on lattice cluster
      theory. We performed hypothetical calculations for a variety of repeat unit
      structures. We also investigated the correlation between the interaction energy
      and extending or reducing the chain length of the polymer repeat unit using
      COMPASS force fields. Our results indicate that the ionic conductivity of the
      nonpolar CF(2)CF(2) group in the main chain varies with the length of the chain.
      In addition, the ionic conductivity of different CF(2)CF(2) group chain lengths
      fluctuates according to hydration level. When OCF(2)CF(3)CF groups are
      substituted at 0 and 1, the predictions of the PFSA membrane agreed well with the
      experimental data from a Dow membrane. To obtain good ionic conductivity at a
      high vapor equilibrated hydration level, the nonpolar group in the polymer repeat
      unit and the substituted group chain connecting the nonpolar group length should
      both be short, and the substituted group chain connected with the sulfonic group
      should be long.

PMID- 19586119
TI  - Molecular dynamics simulations of concentrated polymer solutions in thin film
      geometry. I. Equilibrium properties near the glass transition.
AB  - We report on results of molecular dynamics simulations for supported polymer
      films with explicit solvent. The simulation represents the polymers by bead
      spring chains and the solvent particles by monomers. The interaction between
      polymer and solvent favors mixing. We find that the solvent acts as a
      plasticizer. The glass transition temperature T(g) is reduced relative to the
      pure polymer film. Near T(g) we explore equilibrium properties as a function of
      temperature and solvent concentration. We find that the structure and dynamics of
      the films are spatially heterogeneous. The solvent density is enriched at the
      supporting wall and at the free surface where the film is in equilibrium with
      solvent vapor. At both interfaces the solvent dynamics is fast, but smoothly
      crosses over to bulk dynamics when moving from the interfaces toward the center
      of the film. A smooth gradient from enhanced dynamics at the interfaces to bulk
      behavior in the film center is also found for the monomers. We show that the same
      formula used to parametrize the spatial gradient of the dynamics in the pure
      polymer film may also be applied here. Furthermore, we determine the
      concentration dependence of the relaxation time of the solvent in the center of
      film and compare this dependence to models proposed in literature.

PMID- 19586120
TI  - Molecular dynamics simulations of concentrated polymer solutions in thin film
      geometry. II. Solvent evaporation near the glass transition.
AB  - We perform molecular dynamics simulations of a coarse-grained model of a polymer
      solvent mixture to study solvent evaporation from supported and freestanding
      polymer films near the bulk glass transition temperature T(g). We find that the
      evaporation process is characterized by three time (t) regimes: An early regime
      where the initially large surplus of solvent at the film-vapor interface
      evaporates and the film thickness h varies little with t, an intermediate regime
      where h decreases strongly, and a final regime where h slowly converges toward
      the asymptotic value of the dry film. In the intermediate regime the decrease of
      h goes along with an increase of the monomer density at the retracting interface.
      This polymer-rich "crust" is a nonequilibrium effect caused by the fast
      evaporation rate in our simulation. The interfacial excess of polymer gradually
      vanishes as the film approaches the dry state. In the intermediate and final time
      regimes it is possible to describe the simulation data for h(t) and the solvent
      density profile phi(L)(y,t) by the numerical solution of a one-dimensional
      diffusion model depending only on the y direction perpendicular to the interface.
      The key parameter of this model is the mutual diffusion coefficient D(L) of the
      solvent in the film. Above T(g) we find that a constant D(L) allows to describe
      the simulation data, whereas near T(g) agreement between simulation and modeling
      can only be obtained if the diffusion coefficient depends on y through two
      factors: A factor describing the slowing down of the dynamics with decreasing
      solvent concentration phi(L)(y,t) and a factor parametrizing the smooth gradient
      toward enhanced dynamics as the film-vapor interface is approached.

PMID- 19586121
TI  - Mechanical testing of glassy and rubbery polymers in numerical simulations: role
      of boundary conditions in tensile stress experiments.
AB  - We use coarse-grained molecular dynamics simulations to perform tensile test
      deformation on glassy and rubbery polymer samples using two types of driving for
      the deformation. We compare the outcome from a standard homogeneous deformation
      procedure with that of a boundary driven procedure in which the sample is driven
      by the nanometric equivalent of grips. No significant difference is observed in
      both uniaxial and triaxial tensile experiments. Implications for testing the
      behavior of nonhomogeneous polymer materials are briefly discussed.

PMID- 19586122
TI  - Energetics investigation on encapsulation of protein/peptide drugs in carbon
      nanotubes.
AB  - This work focuses on the dynamic properties and energetics of the protein/peptide
      drug during its transport through carbon nanotubes (CNTs). A systematic study was
      performed on the interaction between the peptide and the CNTs. In the molecular
      dynamics (MD) simulations, the protein/peptide molecule Zadaxin is observed to be
      encapsulated inside the nanotube after its spontaneous insertion and oscillates
      around the center of the tube, where the van der Waals interaction energy is
      observed to be a minimum. Furthermore, it is found by performing steered MD
      simulations that the pulling force applied to the peptide reaches a maximum
      value, which demonstrates the ability of the CNTs to trap protein/peptide drugs.
      Such effects, attributed to van der Waals interactions, can be influenced by
      varying the lengths and diameters of the CNTs. Longer nanotubes provide a broader
      area to trap the peptide, while smaller nanotubes are able to encapsulate the
      peptide with a deeper interaction energy well. This investigation provides
      insights into nanoscale pharmaceutical drug delivery devices.

PMID- 19586123
TI  - Self-assembly of actin monomers into long filaments: Brownian dynamics
      simulations.
AB  - Brownian dynamics simulations are used to study the dynamical process of self
      assembly of actin monomers into long filaments containing up to 1000 actin
      protomers. In order to overcome the large separation of time scales between the
      diffusive motion of the free monomers and the relatively slow attachment and
      detachment processes at the two ends of the filaments, we introduce a novel
      rescaling procedure by which we speed all dynamical processes related to actin
      polymerization and depolymerization up by the same factor. In general, the actin
      protomers within a filament can attain three different states corresponding to a
      bound adenosine triphosphate (ATP), adenosine diphosphate with inorganic
      phosphate (ADP/P), and ADP molecule. The simplest situation that has been studied
      experimentally is provided by the polymerization of ADP-actin, for which all
      protomers are identical. This case is used to unravel certain relations between
      the filament's physical properties and the model parameters such as the
      attachment rate constant and the size of the capture zone, the detachment rate
      and the probability of the detached event, as well as the growth rate and waiting
      times between two successive attachment/detachment events. When a single filament
      is allowed to grow in a bath of constant concentration of free ADP-actin
      monomers, its growth rate increases linearly with the free monomer concentration
      in quantitative agreement with in vitro experiments. The results also show that
      the waiting time is governed by exponential distributions and that the two ends
      of a filament undergo biased random walks. The filament length fluctuations are
      described by a length diffusion constant that is found to attain a constant value
      at low ADP-actin concentration and to increase linearly with this concentration.
      It is straightforward to apply our simulation code to more complex processes such
      as polymerization of ATP-actin coupled to ATP hydrolysis, force generation by
      filaments, formation of filament bundles, and filament-membrane interactions.

PMID- 19586124
TI  - Peptide aggregation and solvent electrostriction in a simple zwitterionic
      dipeptide via molecular dynamics simulations.
AB  - We investigate the structure of the glycyl-l-alanine dipeptide in aqueous
      solution at a 1:20 peptide:water concentration via classical, atomistic molecular
      dynamics simulations using the CHARMM22 force field, and compare to recent
      neutron diffraction data [S. E. McLain, A. K. Soper, and A. Watts, Eur. Biophys.
      J. 37, 647 (2008); S. E. McLain, A. K. Soper, I. Diadone, J. C. Smith, and A.
      Watts, Angew. Chem. Int. Ed. 47, 9059 (2008)]. Comparison between simulations and
      experiments is made using the static structure factor S(Q). The effect of water
      model (TIP3P, TIP4P, and SPC/E) upon the solution structure is investigated.
      Agreement between experiment and simulation is generally good across the entire Q
      range, although some model-dependent variation is observed, particularly in the
      predicted intensities of features in S(Q). Peptide aggregation is found to be
      driven by "hydrophilic" (often bifurcated) hydrogen bonds formed between carboxy
      and amine functional groups, although simulations suggest that the degree of
      aggregation is less than that observed experimentally. It is found that
      hydrophobic association is not significant, with hydrophobic hydration being
      preferred to association. Detailed examination of the solute structural motifs
      reveals the existence of bifurcated motifs that are suggested to be an artifact
      of the CHARMM force field, and may imply that classical force fields provide a
      flawed structural and dynamical description of such molecular fluids.
      Investigation of the water structure reveals the presence of an electrostrictive
      effect which manifests itself as an increase in the number of interstitial
      molecules in the water second coordination shell, in contradiction to suggestions
      that this phenomenon arises owing to hydrogen bond bending. Detailed analysis
      based upon two-dimensional distribution functions suggests an intimate link
      between the phenomenon of electrostriction and the behavior of water under high
      pressure compression. We find the magnitude of the electrostrictive effect
      inferred from the neutron diffraction data to be greater than that found in the
      simulations. Investigation of the solvation structure suggests that the CHARMM
      force field overhydrates the terminal carboxy group, and that this overhydration
      is accompanied by the presence of bifurcated hydrogen bonds.

PMID- 19586125
TI  - Analysis of the nucleotide-dependent conformations of kinesin-1 in the hydrolysis
      cycle.
AB  - Kinesin-1 motion on a microtubule (MT) is still receiving a great attention due
      to its relevance in understanding molecular motion triggered by adenosine
      triphosphate (ATP) hydrolysis. Recent experimental data on kinesin-tubulin
      nucleotide interactions have clarified some of the conformational details
      involved in the hydrolysis process [T. Mori et al., Nature (London) 450, 750
      (2007)]. Specifically, fluorescence resonance energy transfer was used to measure
      the affinity of motor domains to tubulin heterodimers. Our work is directly
      devoted to understand and reproduce the main output of these experiments as well
      as to go beyond and give a global dynamical picture of the whole hydrolysis
      cycle. We predict that phosphate groups have the ability to confine to the
      tubulin domains in order to explain the delay between ATP hydrolysis and head
      detaching, which seems crucial for the achievement of processivity. In our
      approach me make use of chemical kinetics complemented with stochastic molecular
      simulations of the elements involved.

PMID- 19586126
TI  - Linear and nonlinear magneto-optics of ferritin.
AB  - Measurements of Rayleigh light scattering and Cotton-Mouton (CM) effect are
      carried out at room temperature for 100 mM NaCl solutions of apoferritin/ferritin
      loaded with 0, 90, 100, 500, 700, and 1500 Fe atoms/molecule. Because of the
      spherical shape, ferritin macromolecule should not manifest magnetic anisotropy;
      however, in solution it shows the induced magnetic birefringence (CM effect) and
      changes in intensity of the scattered light components. The newly obtained data
      support the previously reported conclusions indicating that the deformation of
      linear optical polarizability induced in the ferritin by a magnetic field and the
      orientation of the induced magnetic dipole moment by this field are the main
      sources of the magneto-optical phenomena observed. Nevertheless, it is also found
      that the orientation of the permanent magnetic dipole moment contributes to both
      effects. The magnetic field induced changes in the light scattering and the CM
      effect theoretically depend on the linear magneto-optical polarizability, chi, on
      the nonlinear magneto-optical polarizability, eta, and square of the permanent
      magnetic dipole moment value of the macromolecule, mu(2). On the basis of the
      theory describing both effects as well as the experimental data, the values of
      the anisotropy of linear magneto-optical polarizabilities components, the values
      of the linear optical polarizability and its anisotropy, nonlinear magneto
      optical polarizability and its anisotropy, are estimated. Also the magnetic
      dipole moment of the ferritin macromolecule is found. Interestingly, not all iron
      atoms in the ferritin are indicated to be in the superparamagnetic state, some of
      them occur in the diamagnetic form.

PMID- 19586127
TI  - Erratum: "A direct test of the correlation between elastic parameters and
      fragility of ten glass formers and their relationship to elastic models of the
      glass transition" [J. Chem. Phys. 130, 064502 (2009)].

PMID- 19586128
TI  - Publisher's Note: "Four-component relativistic theory for NMR parameters: unified
      formulation and numerical assessment of different approaches" [J. Chem. Phys.
      130, 144102 (2009)].

PMID- 19586129
TI  - Erratum: "Zero kinetic energy photoelectron spectra of the allyl radical, C3H5"
      [J. Chem. Phys. 113, 561 (2000)].

PMID- 19586130
TI  - Publisher's Note: "Improving the accuracy of the nonlocal van der Waals density
      functional with minimal empiricism" [J. Chem. Phys. 130, 104105 (2009)].

PMID- 19586131
TI  - Multigenerational exposure of the estuarine sheepshead minnow (Cyprinodon
      variegatus) to 17beta-estradiol. II. Population-level effects through two life
      cycles.
AB  - The evaluation of multigeneration, population-level impacts is particularly
      important in the risk assessment of endocrine-disrupting compounds, because
      adverse effects may not be evident during the first generation of exposure.
      Population models were developed for the sheepshead minnow (Cyprinodon
      variegatus) exposed to 17beta-estradiol (E2) for two complete generations (F1 and
      F2) to determine population-level effects of multigenerational exposure to a
      model estrogen. Stage-structured matrix models were used to determine
      interactions between treatment and the number of generations exposed.
      Reproduction was significantly reduced in both the 0.08 and 0.2 MUg E2/L
      treatments in both generations, and embryo and larval stages experienced reduced
      survival at 0.2 MUg/L in the second generation only. However, increased female to
      male sex ratio in these treatments compensated for the loss in reproductive
      output, and significant population-level effects only occurred in the 0.2 MUg
      E2/L treatment of the F2 population. The F2 population in the 0.2 MUg E2/L
      treatment also had an altered, stable stage distribution relative to the control
      population of both generations and the Fl population in the 0.2 MUg E2/L
      treatment, resulting in additional population-level effects. These results
      demonstrate that continued exposure to E2 had compounding effects on sheepshead
      minnow populations and that long-term exposures may be necessary to understand
      the risk that exposures to environmental estrogens pose to native populations.
      Although population-level effects did not occur in the Fl generation, a risk
      decision based on Fl organism-level effects would be protective of the population
      exposed for two generations.

PMID- 19586133
TI  - IGF2 is highly expressed in pediatric undifferentiated sarcomas and reveals two
      distinct cytoplasmic trafficking patterns.
AB  - Pediatric undifferentiated soft tissue sarcomas (USTSs) are tumors composed of
      primitive mesenchymal cells. As such, they form an attractive model for studying
      the early events in sarcoma development. In an effort to better understand the
      critical molecular aberrations leading to sarcoma development, gene expression
      array analysis and post-array validation techniques were applied to several
      USTSs; the results were consistent with upregulation of the excitatory components
      of the insulin-like growth factor (IGF) pathway. Particularly high expression of
      the insulin-like growth factor 2 (IGF2) ligand was seen and confirmed by real
      time reverse transcriptase-polymerase chain reaction. Immunohistochemistry
      performed using antibodies against IGF2 revealed overexpression of the IGF2
      protein in 19 of 21 (90%) USTSs and revealed 2 distinct staining patterns, 1 in
      which there was diffuse cytoplasmic staining (16/19) and 1 in which there was
      punctate perinuclear positivity (3/19). Using ultrastructural immunogold
      localization of IGF2, it was determined that IGF2 was primarily localized to
      Golgi-derived vesicles and multivesicular bodies in tumor cells showing the
      punctate pattern, and to both the cytoplasm and plasma membrane of tumor cells
      showing the diffuse pattern. The results suggest that upregulation of the IGF
      pathway in pediatric USTSs is a critical early event in the development of
      sarcomas. Furthermore, findings from the immunocytochemical and immunogold
      analyses confirm the presence of 2 different cytoplasmic trafficking patterns and
      storage motifs of IGF2 within this type of tumor. Given that in one subcellular
      pattern the IGF2 protein does not appear to reach the membrane, these findings
      may have functional significance.

PMID- 19586134
TI  - Dyssegmental dysplasia with bone entrapment and visceral ramifications.
AB  - A stillborn neonate had the typical clinical and radiologic manifestations of
      dyssegmental dysplasia, an autosomal recessive genetic disorder. The diagnosis
      was supported by histologic demonstration of the characteristic ballooned
      chondrocytes in the growth plate and spaces filled with mucoid material in the
      resting cartilage. Autopsy revealed entrapment of the femoral heads by bone
      overgrowth in the acetabulum. This notable feature, which has apparently not
      previously been documented, explained the articular rigidity, which is a
      significant clinical manifestation. Horizontal grooves on the anterior surface of
      the spleen were another unusual finding. Our observations further emphasize the
      importance of comprehensive autopsy in the determination of the pathogenesis of
      the clinical features and the range of phenotypic expression of an underlying
      mutation in an unusual genetic disorder.

PMID- 19586135
TI  - Readiness to change as a mediator of the effect of a brief motivational
      intervention on posttreatment alcohol-related consequences of injured emergency
      department hazardous drinkers.
AB  - Brief motivational interventions (BMIs) are usually effective for reducing
      alcohol use and consequences in primary care settings. We examined readiness to
      change drinking as a mediator of the effects of BMI on alcohol-related
      consequences. Participants were randomized into three conditions: (a) standard
      care plus assessment (SC), (b) SC plus BMI (BI), and (c) BI plus a booster
      session (BIB). At 12-month follow-up BIB patients had significantly reduced
      alcohol consequences more than had SC patients. Patients receiving BI or BIB
      maintained higher readiness scores 3 months after treatment than did patients
      receiving SC. However, readiness mediated treatment effects only for those highly
      motivated to change prior to the intervention but not for those with low pre
      intervention motivation. BI and BIB for these patients decreased alcohol
      consequences in part because they enhanced and maintained readiness for those
      highly motivated prior to the intervention, but not for those with low
      motivation. Results are opposite of what would be expected from MI theory. An
      alternative explanation is offered as to why this finding occurred with this
      opportunistically recruited Emergency Department patient population.

PMID- 19586137
TI  - Interpersonal problems and negative mood as predictors of within-day time to
      drinking.
AB  - Using data collected via handheld electronic diaries (EDs), we examined within
      day associations between early-day negative moods and stress and subsequent time
      to drinking. A sample of 97 (n=48 women) adults recruited to participate in a
      drinking-reduction intervention study used EDs to record mood and interpersonal
      problems at randomly selected times during each of 3 reporting intervals and
      drinking as it occurred each day for 21 days. Using multilevel hazard models, we
      tested associations between early-day stress/negative mood ratings and time to
      drinking as well as potential moderating effects of drinking to cope (DTC)
      motives on these associations. Whereas previous analyses of these data showed no
      associations between early-day negative moods and number of drinks consumed later
      in the day, here we found significant associations between negative moods and
      time to drinking. Associations involving negative moods, DTC, and hazard for
      drinking varied depending on time of day, and some mood effects were moderated by
      DTC. These findings suggest that time to drinking may be more sensitive to the
      effects of acute negative mood states than is drinking quantity.

PMID- 19586138
TI  - Body mass index and alcohol consumption: family history of alcoholism as a
      moderator.
AB  - Recent research suggests that excess food consumption may be conceptualized as an
      addictive behavior. Much of the evidence comes from neurobiological similarities
      between drug and food consumption. In addition, an inverse relation between
      alcohol consumption and body mass index (BMI) has been observed. Previous
      research has hypothesized that this inverse relation is attributable to
      competition between food and alcohol for similar neurotransmitter receptors. The
      current study explored this neurobiological hypothesis further by examining the
      influence of an indicator of biological risk associated with alcohol problems
      (family history of alcoholism) on the relationship between alcohol and food
      intake. Data from 37,259 participants in the National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC) were included in the study. BMI, family
      history of alcoholism, gender, and race/ethnicity were assessed as predictors of
      typical drinking frequency and estimated blood alcohol concentration (BAC). An
      inverse relationship between alcohol consumption and BMI was demonstrated. An
      attenuation of family history effects on drinking behavior was evident for obese
      compared to nonobese participants. The results suggest a neurobiological link
      between alcohol use and food consumption, consistent with theories characterizing
      excess food consumption as an addictive behavior.

PMID- 19586136
TI  - Gender differences in acute alcohol effects on self-regulation of arousal in
      response to emotional and alcohol-related picture cues.
AB  - Basic mechanisms through which men and women self-regulate arousal have received
      little attention in human experimental addiction research, although stress
      response-dampening and craving theories suggest an important role of emotional
      arousal in motivating alcohol use. This study examined gender differences in the
      effects of acute alcohol intoxication on psychophysiological and self-reported
      arousal in response to emotionally negative, positive, and neutral, and alcohol
      related, picture cues. Thirty-six social drinkers (16 women) were randomly
      assigned to an alcohol, placebo, or control beverage group and exposed to picture
      cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was
      assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically
      significant beverage group-by-gender interaction effect on psychophysiological,
      but not self-reported, arousal was found. The 0.1-Hz HRV responses to picture
      cues were suppressed by alcohol only in men. This gender-specific suppression
      pattern did not differ significantly across picture cue types. There were no
      significant gender differences in the placebo or control group. Greater dampening
      of arousal by alcohol intoxication in men, compared with women, may contribute to
      men's greater tendency to use alcohol to cope with stress.

PMID- 19586139
TI  - Coping-anxiety and coping-depression motives predict different daily mood
      drinking relationships.
AB  - Individuals with different drinking motives show distinctive patterns of alcohol
      use and problems. Drinking to cope, or endorsing strong coping motives for
      alcohol use, has been shown to be particularly hazardous. It is important to
      determine the unique triggers associated with coping drinking. One limitation of
      past research has been the failure to contend with the complexities inherent in
      coping motives. Using the Modified Drinking Motives Questionnaire-Revised (Grant,
      Stewart, O'Connor, Blackwell, & Conrod, 2007), which separates coping-anxiety and
      coping-depression motives, we investigated whether these motives moderated
      relationships between daily mood and subsequent drinking (statistically
      controlling for sex, baseline anxious and depressive symptomatology, initial
      alcohol problems, and additional drinking motives). College students (N=146)
      provided daily reports of mood and alcohol consumption online for 3 weeks.
      Multilevel modeling analyses revealed that, as hypothesized, stronger initial
      coping-depression motives predicted higher daily depressed mood-alcohol
      consumption slopes. Also consistent with expectation, stronger initial coping
      anxiety motives predicted higher anxious mood-alcohol consumption slopes. We
      discuss how this identification of the unique mood triggers associated with each
      type of coping drinking motive can provide the basis for targeted interventions.

PMID- 19586140
TI  - Acute alcohol tolerance on subjective intoxication and simulated driving
      performance in binge drinkers.
AB  - High rates of binge drinking and alcohol-related problems, including drinking and
      driving, occur among college students. Underlying reasons for the heightened
      impaired driving rates in this demographic group are not known. The authors
      hypothesized that acute tolerance to the interoceptive cues of intoxication may
      contribute to these maladaptive decisions to drive in binge drinkers. Groups of
      binge-drinking and non-binge-drinking college students (N = 28) attended sessions
      during which they received a moderate dose of alcohol (0.65 g/kg) or a placebo.
      The development of acute tolerance to subjective ratings of intoxication and
      simulated driving performance was assessed by comparing measures taken during the
      ascending phase and descending phases of the blood alcohol curve. Compared with
      placebo, alcohol increased ratings of intoxication and impaired multiple aspects
      of simulated driving performance in both binge and non-binge drinkers. During the
      descending phase of the blood alcohol curve, binge drinkers showed acute
      tolerance to alcohol's effect on subjective intoxication, and this effect was
      accompanied by an increased rating of willingness to drive. By contrast, non
      binge drinkers showed no acute tolerance.

PMID- 19586142
TI  - Facilitating outpatient treatment entry following detoxification for injection
      drug use: a multisite test of three interventions.
AB  - A multisite, randomized trial within the National Drug Abuse Treatment Clinical
      Trials Network (CTN) was conducted to test 3 interventions to enhance treatment
      initiation following detoxification: (a) a single session, therapeutic alliance
      intervention (TA) added to usual treatment; (b) a 2-session, counseling and
      education, HIV/HCV risk reduction intervention (C&E), added to usual treatment;
      and (c) treatment as usual (TAU) only. Injection drug users (n=632) enrolled in
      residential detoxification at 8 community treatment programs were randomized to 1
      of the 3 study conditions. TA participants reported entering outpatient treatment
      sooner and in greater numbers than TAU participants. Reported treatment entry for
      C&E fell between TA and TAU with no significant differences between C&E and the
      other conditions. There were no differences among the interventions in retention,
      as measured by weeks of outpatient treatment for all participants who reported
      treatment entry. Alliance building interventions appear to be effective in
      facilitating transfer from detoxification to outpatient treatment, but additional
      treatment engagement interventions may be necessary to improve retention.

PMID- 19586141
TI  - Alcohol outcome expectancies as socially shared and socialized beliefs.
AB  - Alcohol expectancies are important predictors of alcohol involvement in both
      adolescents and adults, yet little research has examined the social origins and
      transmission of these beliefs. This paper examined alcohol outcome expectancies
      collected in a cohort-sequential longitudinal study of 452 families with children
      followed over seven waves. Children completed interviews every 6 months, and
      parents completed interviews annually. Eighteen of 27 alcohol expectancies were
      highly consensual, being endorsed by significantly more than 67% of the mothers
      and fathers. These consensual expectancies were also highly stable over a 3-year
      period. Over the same period, children increased their adoption of both the
      positive and negative consensual alcohol expectancies. Unconditional latent
      growth modeling showed that piece-wise growth models with a transition at age 12
      fit the data best. Both the positive and negative consensual expectancies were
      adopted at a faster rate between ages 8.5 and 11.5 than between ages 12 and 13.5.
      For negative expectancies, there was no further growth between ages 12 and 13.5.
      Taken together, these findings support the conceptualization of alcohol outcome
      expectancies as socially shared and transmitted beliefs.

PMID- 19586143
TI  - Validation of scales measuring attitudes, self-efficacy, and intention related to
      smoking among middle school students.
AB  - Attitudes toward smoking, self-efficacy to avoid smoking, and smoking intention,
      widely cited correlates of youth smoking prevention, are often measured in large
      scale youth tobacco surveys. The psychometric properties of these scales have not
      been well studied among middle school youth. We examined the factorial,
      discriminate, and convergent validity of these scales among sixth to eighth
      graders from a convenience sample of 22 Texas middle schools (51.2% female;
      51.21% White, 32.1% Hispanic, 16.9% African American, and 8.8% Other; 67.8%
      nonsmokers, 21.9% experimental smokers; 3.3% former smokers; and 7.6% current
      smokers). Confirmatory factor analysis and invariance testing suggest that
      smoking attitudes, self-efficacy, and intention have evidence of construct
      validity in this multiethnic sample, and the scales are appropriate to assess
      these constructs among middle school adolescents. Additional studies are needed
      to establish additional evidence of validity of these constructs in other middle
      school samples and other subgroups (e.g. current, experimental, and former
      smokers).

PMID- 19586145
TI  - Winning and positive affect can lead to reckless gambling.
AB  - Experiments 1 and 2 examined whether winning versus losing led to reckless
      betting for real prize money. Experiment 2 also assessed whether positive or
      negative emotions were linked to such reckless betting. College students were
      randomly assigned to experience primarily either wins or losses during the rigged
      first round of a computerized card tournament that had 2 independent rounds. For
      the second round, participants' chip totals were reset and cards were dealt
      randomly. In Experiment 1 (N=107), participants in the Initial-Winning, as
      compared with the Initial-Losing, condition bet more recklessly (i.e., bet too
      many chips when a loss was likely). Experiment 2 (N=72) again showed that Initial
      Winning participants bet significantly more recklessly than did Initial-Losing
      participants. It also revealed that positive affect was significantly positively
      correlated with such reckless betting. These findings have implications for
      understanding how college students, those at an age when they are especially
      vulnerable to problem gambling, can come to lose more money than they can afford.
      Initially winning and positive affect when gambling could be risk factors.

PMID- 19586146
TI  - Gambling, gambling activities, and problem gambling.
AB  - This research examined similarities and differences between gambling activities,
      with a particular focus on differences in gambling frequency and rates of problem
      gambling. The data were from population-based surveys conducted in Canada between
      2001 and 2005. Adult respondents completed various versions of the Canadian
      Problem Gambling Index (CPGI), including the Problem Gambling Severity Index
      (PGSI). A factor analysis of the frequency with which different gambling
      activities were played documented the existence of two clear underlying factors.
      One factor was comprised of Internet gambling and betting on sports and horse
      races, and the other factor was comprised of lotteries, raffles, slots/Video
      Lottery Terminals (VLTs), and bingo. Factor one respondents were largely men;
      factor two respondents were more likely to be women and scored significantly
      lower on a measure of problem gambling. Additional analyses indicated that (1)
      frequency of play was significantly and positively related to problem gambling
      scores for all activities except raffles, (2) the relationship between problem
      gambling scores and frequency of play was particularly pronounced for slots/VLTs,
      (3) problem gambling scores were associated with playing a larger number of
      games, and (4) Internet and sports gambling had the highest conversion rates
      (proportion who have tried an activity who frequently play that activity).

PMID- 19586144
TI  - The effect of body image threat on smoking motivation among college women:
      mediation by negative affect.
AB  - A recent experimental study found that activation of negative body image
      cognitions produced urges to smoke in young women (E. N. Lopez, D. J. Drobes, J.
      K. Thompson, & T. H. Brandon, 2008). This study intended to replicate and extend
      these experimental findings by examining the role of negative affect as a
      mediator of the relationship between body dissatisfaction and smoking urges.
      Female college smokers (N=133) were randomly assigned to a body image challenge
      (trying on a bathing suit) or a control condition (evaluating a purse). State
      levels of urge to smoke, mood, and body dissatisfaction were assessed both pre-
      and postmanipulation. Trying on a bathing suit increased body dissatisfaction and
      reported urges to smoke, particularly those urges related to reducing negative
      affect. Additionally, state negative affect mediated the relationship between the
      body image manipulation and smoking urge. This study provides additional support,
      through an experimental design, that situational challenges to body image
      influence smoking motivation and that this effect occurs, at least in part,
      through increases in negative affect. Theoretical and applied implications are
      discussed.

PMID- 19586147
TI  - Substance use after residential treatment among individuals with co-occurring
      disorders: the role of anxiety/depressive symptoms and trauma exposure.
AB  - This longitudinal study examined the contribution of anxiety/depressive symptoms
      and lifetime and recent trauma exposure to substance use after residential
      substance abuse treatment among individuals with co-occurring disorders. Data
      were collected from adults at treatment entry and 6 and 12 months later. At
      treatment entry, nearly all participants reported lifetime trauma exposure, and
      over one third met criteria for posttraumatic stress disorder (PTSD). Over the
      follow-up, nearly one third of the participants were exposed to trauma. Lifetime
      trauma exposure and a diagnosis of PTSD at treatment entry were not associated
      with substance use over the follow-up. Trauma exposure and anxiety/depressive
      symptoms over the follow-up were associated with an increased likelihood of
      substance use. Gender did not moderate the association between trauma exposure
      and anxiety/depressive symptoms and substance use. These findings highlight the
      importance of monitoring for trauma exposure and symptoms of anxiety/depression
      to better target interventions and continuing care approaches to reduce the
      likelihood of posttreatment substance use in this population.

PMID- 19586148
TI  - Behavioral inhibition and activation systems: differences in substance use
      expectancy organization and activation in memory.
AB  - We used multidimensional scaling to model the semantic network of alcohol and
      marijuana expectancies (N=897). Preference mapping was used to estimate vectors
      representing patterns of activation through the network as a function of levels
      of behavioral inhibition (BIS) and behavioral activation (BAS). Individuals with
      low BIS combined with high BAS levels exhibited patterns of activation
      emphasizing behavioral activation similar to heavier drug users in previous
      research. High BIS, low BAS individuals exhibited activation patterns with
      greater emphasis on inhibitory expectancies similar to low-level users.
      Differences in expectancy activation patterns were maintained after controlling
      for substance use and gender. Individual differences in BIS/BAS are associated
      with the organization of semantic networks and patterns of activation of
      expectancies contributing to differences in substance use behavior.

PMID- 19586149
TI  - Alcohol expectancy priming and drinking behavior: the role of compatibility
      between prime and expectancy content.
AB  - According to information-processing models of alcohol use, alcohol expectancies
      constitute representations in long-term memory that may be activated in the
      presence of drinking-related cues, thereby influencing alcohol consumption. A
      fundamental implication of this approach is that primed expectancies should
      affect drinking only for those individuals who possess the specific expectancies
      primed. To test this notion, in the present study, participants were initially
      assessed on 3 distinct domains of positive alcohol expectancies. Approximately 1
      week later, they completed an ad libitum drinking study during which only a
      single expectancy domain (sociability) was primed in the experimental condition.
      Consistent with predictions, following exposure to sociability primes but not
      control primes, individuals with stronger expectancies that alcohol would enhance
      sociability uniquely showed increased placebo consumption of nonalcoholic beer.
      These results, which demonstrate the moderating role of compatibility between the
      specific content of primes and that of underlying expectancies, offer new, direct
      support for memory network-based models of drinking behavior.

PMID- 19586150
TI  - Drinking and desired self-images: path models of self-image goals, coping
      motives, heavy-episodic drinking, and alcohol problems.
AB  - Coping motives for drinking initiate alcohol-related problems. Interpersonal
      goals, which powerfully influence affect, could provide a starting point for this
      relation. Here we tested effects of self-image goals (which aim to construct and
      defend desired self-views) and compassionate goals (which aim to support others)
      on heavy-episodic drinking and alcohol-related problems. Undergraduate drinkers
      (N=258) completed measures of self-image and compassionate goals in academics and
      friendships, coping and enhancement drinking motives, heavy-episodic drinking,
      and alcohol-related problems in a cross-sectional design. As predicted, self
      image goals, but not compassionate goals, positively related to alcohol-related
      problems. Path models showed that self-image goals relate to coping motives, but
      not enhancement motives; coping motives then relate to heavy-episodic drinking,
      which in turn relate to alcohol-related problems. Self-image goals remained a
      significant predictor in the final model, which accounted for 34% of the variance
      in alcohol-related problems. These findings indicate that self-image goals
      contribute to alcohol-related problems in college students both independently and
      through coping motives. Interventions can center on reducing self-image goals and
      their attendant negative affect.

PMID- 19586151
TI  - Family conflict and depression in HIV-negative heterosexuals: the role of
      methamphetamine use.
AB  - Previous research has reported elevated levels of depressive symptoms among
      methamphetamine users, but little attention has been paid to possible links
      between family environment and psychological distress. This study examined
      relationships between family conflict, substance use, and depressive symptoms in
      a sample of 104 heterosexual methamphetamine users in San Diego, California.
      Eighty-nine percent of the sample reported conflict with a family member in the
      past year. Conflict was reported most often with parents and siblings. Sources of
      conflict included drug use, lifestyle issues, interpersonal and communication
      issues, and concern for other family members. In regression analyses, being
      female, being a polydrug user, and facing social and legal stressors were
      associated with higher levels of family conflict. Multiple regression analyses
      also revealed a positive association between family conflict and depressive
      symptoms. Contrary to expectation, methamphetamine dose did not moderate the
      relationship between family conflict and depressive symptoms. Reducing family
      conflict may be an important first step toward ameliorating depressive symptoms
      and creating more supportive environments for methamphetamine users who are in
      urgent need of effective interventions.

PMID- 19586152
TI  - Positive urgency predicts illegal drug use and risky sexual behavior.
AB  - There are several different personality traits that dispose individuals to engage
      in rash action. One such trait is positive urgency: the tendency to act rashly
      when experiencing extremely positive affect. This trait may be relevant for
      college student risky behavior, because it appears that a great deal of college
      student risky behavior is undertaken during periods of intensely positive mood
      states. To test this possibility, the authors conducted a longitudinal study
      designed to predict increases in risky sexual behavior and illegal drug use over
      the course of the first year of college (n=407). In a well-fitting structural
      model, positive urgency predicted increases in illegal drug use and risky sexual
      behavior, even after controlling for time 1 (T1) involvement in both risky
      behaviors, biological sex, and T1 scores on four other personality dispositions
      to rash action. The authors discuss the theoretical and practical implications of
      this finding.

PMID- 19586153
TI  - Changes in tobacco use among adolescent smokers in substance abuse treatment.
AB  - Adolescents with substance use disorders (SUDs) smoke cigarettes more than youth
      in the general population. Little is known about changes in smoking patterns
      during and after outpatient SUD treatment. We examined whether receiving SUD
      treatment had a differential impact on cigarette smoking behaviors of mild (<10
      cigarettes per day [CPD]), moderate (10-19 CPD), and heavy (>or=20 CPD) smokers
      (smoked on >or=60 days in the past 90). Our sample included 378 adolescents from
      the Cannabis Youth Treatment study, who were assessed at intake, and after 3, 6,
      9, and 12 months. Results indicate that after controlling for the effect of
      changes in cannabis use, mild smokers decreased days of smoking during treatment
      and follow-up, whereas moderate and heavy smokers demonstrated a small decrease
      over treatment, and no change over follow-up. Heavy smokers demonstrated a slight
      decrease in CPD during the treatment phase. These results suggest that, whereas
      cigarette smoking may decrease for mild smokers while in SUD treatment, the
      addition of specialized smoking interventions may be necessary to effect change
      in cigarette smoking for moderate and heavy smokers.

PMID- 19586154
TI  - Situational temptation scores and smoking cessation in general care.
AB  - The construct of self-efficacy, which is assessed either in confidence- or
      temptation-related instruments, presumably predicts transitions between the
      transtheoretical model stages of change and ultimately smoking cessation outcome.
      To elucidate its predictive potential for smoking cessation in a general care
      setting, we examined the association of baseline scores of the situational
      temptations inventory with month 12 smoking status in 577 heavy smokers
      participating in a cluster-randomized study of physician training and financial
      incentives for smoking cessation in Germany. At follow-up, abstinence could be
      validated in 56 patients. The temptation sub- and total scores were not
      bivariately associated with altered odds of smoking cessation, in contrast to
      established predictors like the Fagerstrom test of nicotine dependence and the
      stages of change. They were associated with the Fagerstrom scores, but not with
      the stages of change. Controlling for both cessation predictors, in particular
      the positive/social temptation subscore was associated with quitting. Additional
      studies are needed to fully understand how situational temptations relate to
      smoking cessation outcomes and explain variance beyond that of more established
      predictors of cessation.

PMID- 19586155
TI  - Timeline follow-back versus global self-reports of tobacco smoking: a comparison
      of findings with nondaily smokers.
AB  - Methods assessing nondaily smoking are of concern because biochemical measures
      cannot verify self-reports beyond 7 days. This study compared 2 self-reported
      smoking measures for nondaily smokers. A total of 389 college students (48%
      women, 96% White, mean age=19 years) smoking between 1 and 29 days out of the
      past 30 completed computer assessments in 3 cohorts, with the order of
      administration of the measures counterbalanced. Values from the 2 measures were
      highly correlated. Comparisons of timeline follow-back (TLFB) with the global
      questions for the total sample of nondaily smokers yielded statistically
      significant differences (p<.001), albeit small, between measures with the TLFB
      resulting on average in 2.38 more total cigarettes smoked out of the past 30
      days, 0.46 fewer smoking days, and 0.21 more cigarettes smoked per day. Analyses
      by level of smoking showed that the discordance between the measures differed by
      frequency of smoking. Global questions of days smoked resulted in frequent
      reporting in multiples of 5 days, suggesting digit bias. Overall, the 2 measures
      of smoking were highly correlated and equally effective for identifying any
      smoking in a 30-day period among nondaily smokers.

PMID- 19586158
TI  - Does a permissive workplace substance use climate affect employees who do not use
      alcohol and drugs at work? A U.S. national study.
AB  - The goal of this study was to begin exploring the relations of multiple
      dimensions of workplace substance use climate (substance availability, workplace
      descriptive norms, and workplace injunctive norms) to perceived workplace safety,
      work strain, and employee morale among employees who do not use alcohol or drugs
      at work. Data were collected from a probability sample of employed adults in the
      United States (N=2,051) who do not engage in workplace alcohol or drug use. The
      results showed that all three dimensions of workplace substance use climate were
      negatively related to workplace safety, positively related to work strain, and
      negatively related to employee morale. These results suggest that a permissive
      substance use climate at work may have broader relevance for the majority of
      employees who do not use alcohol and drugs at work.

PMID- 19586156
TI  - Beliefs and attitudes about bupropion: implications for medication adherence and
      smoking cessation treatment.
AB  - Beliefs about medication are associated with treatment adherence and outcome.
      This is a secondary analysis of the role of beliefs and attitudes about bupropion
      in treatment adherence and smoking cessation outcomes using data from a smoking
      cessation trial of open-label sustained-release (SR) bupropion therapy reported
      previously (Toll et al., 2007). Positive beliefs and attitudes were positively
      correlated with intentions, desire, confidence, and motivation to quit smoking;
      expectation of quitting success; perceived benefits of quitting; and perceived
      disadvantages of smoking. Positive beliefs were also associated with greater
      medication adherence, an increased likelihood of completing treatment and being
      continuously abstinent, and a delayed latency to smoking lapse. These findings
      provide preliminary support that positive beliefs and attitudes about bupropion
      are associated with positive attitudes toward quitting, better treatment
      adherence, and potentially better treatment response.

PMID- 19586157
TI  - Smokers' expectancies for abstinence: preliminary results from focus groups.
AB  - Smokers' expectancies regarding the effects of cigarette use are powerful
      predictors of smoking motivation and behavior. However, studies have not
      investigated the consequences that smokers expect when they attempt to quit
      smoking: abstinence-related expectancies. The primary goal of this qualitative
      study was to gain initial insight into smokers' expectancies for abstinence.
      Eight focus groups were conducted with 30 smokers diverse with respect to age,
      gender, and ethnoracial background. Content analyses indicated that smokers
      anticipate a variety of outcomes from abstinence. The most frequently reported
      expectancies included pharmacologic withdrawal symptoms, behavioral withdrawal
      symptoms, decreased monetary expense, and immediate improvement of certain
      aspects of physical functioning and health. Additional expectancies concerned
      weight gain, improved attractiveness, enhanced social functioning/self-esteem,
      long-term health outcomes, and loss of relationships. Finally, a number of
      relatively unheralded expectancies were revealed. These involved nicotine
      replacement therapy effectiveness, alcohol and other drug use, cue reactivity,
      cessation-related social support, aversion to smoking, and "political process"
      implications. This study provides a preliminary step in understanding smokers'
      expectancies for abstinence from cigarettes.

PMID- 19586159
TI  - For over a century, Psychological Bulletin has been the leading source of
      systematic review articles for the entire discipline of psychology. Editorial.

PMID- 19586160
TI  - A dual-process model of the alcohol-behavior link for social drinking.
AB  - A dual-process model of the alcohol-behavior link is presented, synthesizing 2 of
      the major social-cognitive approaches: expectancy and myopia theories.
      Substantial evidence has accrued to support both of these models, and recent
      neurocognitive models of the effects of alcohol on thought and behavior have
      provided evidence to support both as well. While proponents of these theories
      have not suggested that they are mutually exclusive views on how alcohol affects
      behavior, attempts to synthesize the 2 have been conspicuously absent. The dual
      process model presented suggests that the alcohol-behavior link is better
      reconceptualized as involving a "preconsumption" and a "consumption" phase. This
      is achieved in the context of contemporary models of automaticity in social
      behavior, emphasizing the commonality of both controlled and automatic processes
      in drinking-related behavior. It is argued that a complete understanding of the
      alcohol-behavior link requires an appreciation of the ways in which the mind may
      become "intoxicated" even in the absence of alcohol consumption. Suggestions for
      further research in this area, testing the present dual-process model of the
      alcohol-behavior link, are also discussed.

PMID- 19586161
TI  - Perceived discrimination and health: a meta-analytic review.
AB  - Perceived discrimination has been studied with regard to its impact on several
      types of health effects. This meta-analysis provides a comprehensive account of
      the relationships between multiple forms of perceived discrimination and both
      mental and physical health outcomes. In addition, this meta-analysis examines
      potential mechanisms by which perceiving discrimination may affect health,
      including through psychological and physiological stress responses and health
      behaviors. Analysis of 134 samples suggests that when weighting each study's
      contribution by sample size, perceived discrimination has a significant negative
      effect on both mental and physical health. Perceived discrimination also produces
      significantly heightened stress responses and is related to participation in
      unhealthy and nonparticipation in healthy behaviors. These findings suggest
      potential pathways linking perceived discrimination to negative health outcomes.

PMID- 19586162
TI  - Feeling validated versus being correct: a meta-analysis of selective exposure to
      information.
AB  - A meta-analysis assessed whether exposure to information is guided by defense or
      accuracy motives. The studies examined information preferences in relation to
      attitudes, beliefs, and behaviors in situations that provided choices between
      congenial information, which supported participants' pre-existing attitudes,
      beliefs, or behaviors, and uncongenial information, which challenged these
      tendencies. Analyses indicated a moderate preference for congenial over
      uncongenial information (d=0.36). As predicted, this congeniality bias was
      moderated by variables that affect the strength of participants' defense
      motivation and accuracy motivation. In support of the importance of defense
      motivation, the congeniality bias was weaker when participants' attitudes,
      beliefs, or behaviors were supported prior to information selection; when
      participants' attitudes, beliefs, or behaviors were not relevant to their values
      or not held with conviction; when the available information was low in quality;
      when participants' closed-mindedness was low; and when their confidence in the
      attitude, belief, or behavior was high. In support of the importance of accuracy
      motivation, an uncongeniality bias emerged when uncongenial information was
      relevant to accomplishing a current goal.

PMID- 19586163
TI  - A meta-analytic investigation of the relationship between attentional bias and
      subjective craving in substance abuse.
AB  - Theoretical models of addiction suggest that attentional bias for substance
      related cues should be associated with self-reported craving. The authors
      evaluated the strength of the association by performing a meta-analysis on 68
      independent data sets from which correlation coefficients between subjective
      craving and attentional bias indices were derived. Additional stratified analyses
      were conducted to identify any variables that might moderate the association
      between craving and attentional bias. The primary meta-analysis indicated a
      significant, albeit weak (r=.19), association between attentional bias and
      craving. Stratified analyses revealed that the association was larger for illicit
      drug and caffeine craving than for alcohol and tobacco craving, larger for direct
      measures of attention (eye movement measures and event-related potential
      measures) than for indirect behavioral measures of attentional bias, and larger
      when craving strength was high than when it was low (all ps<.05). The size of the
      correlation did not differ among patients in treatment and individuals who were
      not seeking treatment. These results suggest that attentional bias and craving
      are related phenomena, although the relationship is generally modest and appears
      to be moderated by various factors. Theoretical implications are discussed.

PMID- 19586164
TI  - Rethinking environmental contributions to child and adolescent psychopathology: a
      meta-analysis of shared environmental influences.
AB  - Behavioral genetic research has concluded that the more important environmental
      influences result in differences between siblings (referred to as nonshared; e2),
      whereas environmental influences that create similarities between siblings
      (referred to as shared; c2) are indistinguishable from zero. However, there is
      mounting evidence that during childhood and adolescence, c2 may make important
      contributions to most forms of psychopathology. The aim of the meta-analysis was
      to empirically confirm this hypothesis. The author examined twin and adoption
      studies (n=490) of internalizing and externalizing psychopathology prior to
      adulthood. Analyses revealed that c2 accounted for 10%-19% of the variance within
      conduct disorder, oppositional defiant disorder, anxiety, depression, and broad
      internalizing and externalizing disorders, regardless of their
      operationalization. When age, informant, and sex effects were considered, c2
      generally ranged from 10%-30% of the variance. Importantly, c2 estimates did not
      vary across twin and adoption studies, suggesting that these estimates reflect
      actual environmental influences common to siblings. The only exception was
      attention-deficit/hyperactivity disorder, which appeared to be largely genetic
      (and particularly nonadditive genetic) in origin. Conceptual, methodological, and
      clinical implications of these findings are discussed.

PMID- 19586166
TI  - Toward an LGBT-informed paradigm for children who break gender norms: comment on
      Drummond et al. (2008) and Rieger et al. (2008).
AB  - In this commentary, the author reviews methodological and conceptual shortcomings
      of recent articles by K. D. Drummond, S. J. Bradley, M. Peterson-Badali, and K.
      J. Zucker (see record 2007-19851-005) as well as G. Rieger, J. A. W. Linsenmeier,
      L. Gygax, and J. M. Bailey (see record 2007-19851-006), which sought to predict
      adult sexual identity from childhood gender identity. The author argues that such
      research needs to incorporate a greater awareness of how stigmatization affects
      identity processes. Multidimensional models of gender identity that describe
      variation in children's responses to pressure to conform to gender norms are
      particularly useful in this regard (S. K. Egan & D. G. Perry, 2001). Experiments
      on the interpretation of developmental data are reviewed to evidence how cultural
      assumptions about sexuality can impact theories of sexual identity development in
      unintended ways. The author concludes that understanding the development of
      children presumed most likely to grow up with sexual minority identities requires
      a consideration of the cultural contexts in which identities develop and in which
      psychologists theorize.

PMID- 19586167
TI  - Childhood gender noncomformity remains a robust and neutral correlate of sexual
      orientation: reply to Hegarty (2009).
AB  - In this issue, P. Hegarty (see record 2009-09998-015) comments on an article by
      G. Rieger, J. A. W. Linsenmeier, L. Gygax, and J. M. Bailey (see record 2007
      19851-006) that compared videos of homosexual and heterosexual people from
      childhood and adulthood. The current authors claim it is reasonable to treat
      masculinity-femininity as a bipolar scale and present justification for the
      approach used in the earlier study. Measures used by Rieger et al. (2008) yielded
      large differences between homosexual and heterosexual participants, and these
      differences are likely to be more meaningful than the low and nonsignificant
      within-group correlations on which Hegarty chose to focus. The authors address
      his suggestion that they are working within a paradigm detrimental to the well
      being of homosexual and gender-nonconforming individuals and suggest that greater
      openness to research such as theirs could have beneficial consequences.

PMID- 19586168
TI  - Troubled meditations on psychosexual differentiation: reply to Hegarty (2009).
AB  - P. Hegarty (see record 2009-09998-015) offered several critiques of the articles
      by G. Rieger, J. A. W. Linsenmeier, L. Gygax, and J. M. Bailey (see record 2007
      19851-006) and K. D. Drummond, S. J. Bradley, M. Peterson-Badali, and K. J.
      Zucker (see record 2007-19851-005) that were published in a Developmental
      Psychology special section entitled "Sexual Orientation Across the Lifespan,"
      guest-edited by C. J. Patterson and R. C. Savin-Williams (2008): (a) reliance on
      a "disease paradigm" (i.e., the use of "medicalizing" language) of lesbian-gay
      bisexual-transgender issues at the expense of a "stigma paradigm," (b)
      endorsement of a developmental linkage between childhood sex-typed behavior and
      later gender identity-sexual orientation, and (c) various sociophilosophical and
      applied matters pertaining to the diagnosis of gender identity disorder in
      children. In this reply, we address these 3 criticisms and argue that an
      interdisciplinary approach, informed by multiple paradigms, will most certainly
      facilitate, not impede, the discovery of answers to many questions about
      psychosexual development for which data are currently lacking.

PMID- 19586170
TI  - Habitual size and projective size: the logic of spatial systems in children's
      drawings.
AB  - The current study analyzed figure size modification in different types of spatial
      context (C. Lange-Kuttner, 1997, Lange-Kuttner, 2004) for sequence and practice
      effects. Children of 7, 9, and 11 years of age, as well as 17-year-olds, drew
      figures in a series of ready-made spatial axes systems, which (a) logically
      increased in dimensional complexity as in child development, (b) were randomized
      in sequence, or (c) were absent, as a control condition for figure size reduction
      through practice. Already 7-year-olds could subtly adapt figure size in the
      logical sequence, but the amount of size reduction stayed within the same size
      range as in the other two conditions. Only at 9 years of age did children show
      sensitivity to spatial constraints, with smaller figures in both the logical and
      random sequence than in the control condition. At 11 years of age, the spatial
      scale of figure size was maximized, particularly so in children who could change
      perspective and construct a bird's-eye view, whereas this effect was attenuated
      in the 17-year-olds. Implications of the results for domain-specific conceptual
      development are discussed.

PMID- 19586169
TI  - Infancy parenting and externalizing psychopathology from childhood through
      adulthood: developmental trends.
AB  - Developmental models and previous findings suggest that early parenting is more
      strongly associated with externalizing problems in early childhood than it is in
      adolescence. In this article, the authors address whether the association of poor
      quality infancy parenting and externalizing problems "rebounds" in adulthood.
      Poor-quality infancy parenting was associated with externalizing problems at
      kindergarten and first grade (mother report) as well as at 23 and 26 years (self
      report). Infancy parenting was not significantly associated with either mothers'
      or youths' reports of externalizing problems at 16 years. These findings are
      consistent with the notion that poor-quality infancy parenting is a risk factor
      for externalizing problems in developmental periods for which externalizing
      behavior is most deviant.

PMID- 19586171
TI  - It takes two to tango: how parents' and adolescents' personalities link to the
      quality of their mutual relationship.
AB  - According to J. Belsky's (1984) process model of parenting, both adolescents' and
      parents' personality should exert a significant impact on the quality of their
      mutual relationship. Using multi-informant, symmetric data on the Big Five
      personality traits and the relationship quality of mothers, fathers, and two
      adolescent children, the current study set out to test this prediction.
      Adolescents' agreeableness and parents' extraversion emerged as predictors of
      relationship warmth, whereas parents' openness emerged as a predictor of low
      restrictive control. In addition, some gender-specific effects emerged. Overall,
      parents' and adolescents' traits equally predicted the amount of relationship
      warmth, whereas adolescents' unique personality more strongly predicted the
      amount of restrictive control. The predictive power of adolescents' personality
      increased with age. Personality characteristics that affected relationship
      quality were partly shared between parents and their adolescent children.
      Findings support Belsky's (1984) notion that both parents' and children's
      personality predict the quality of their mutual relationship, though the relative
      predictive power of children and parents depends on the type of outcome variable
      and the age of the children.

PMID- 19586172
TI  - The protective effects of neighborhood collective efficacy on British children
      growing up in deprivation: a developmental analysis.
AB  - This article reports on the influence of neighborhood-level deprivation and
      collective efficacy on children's antisocial behavior between the ages of 5 and
      10 years. Latent growth curve modeling was applied to characterize the
      developmental course of antisocial behavior among children in the E-Risk
      Longitudinal Twin Study, an epidemiological cohort of 2,232 children. Children in
      deprived versus affluent neighborhoods had higher levels of antisocial behavior
      at school entry (24.1 vs. 20.5, p < .001) and a slower rate of decline from
      involvement in antisocial behavior between the ages of 5 and 10 (-0.54 vs. -0.78,
      p < .01). Neighborhood collective efficacy was negatively associated with levels
      of antisocial behavior at school entry (r = -.10, p < .01) but only in deprived
      neighborhoods; this relationship held after controlling for neighborhood problems
      and family-level factors. Collective efficacy did not predict the rate of change
      in antisocial behavior between the ages of 5 and 10. Findings suggest that
      neighborhood collective efficacy may have a protective effect on children living
      in deprived contexts.

PMID- 19586173
TI  - The contribution of children's self-regulation and classroom quality to
      children's adaptive behaviors in the kindergarten classroom.
AB  - In this study, the authors examined the extent to which children's self
      regulation upon kindergarten entrance and classroom quality in kindergarten
      contributed to children's adaptive classroom behavior. Children's self-regulation
      was assessed using a direct assessment upon entrance into kindergarten. Classroom
      quality was measured on the basis of multiple classroom observations during the
      kindergarten year. Children's adaptive classroom behavior in kindergarten was
      assessed through teacher report and classroom observations: Teachers rated
      children's cognitive and behavioral self-control and work habits during the
      spring of the kindergarten year; observers rated children's engagement and
      measured off-task behavior at 2-month intervals from November to May.
      Hierarchical linear models revealed that children's self-regulation upon school
      entry in a direct assessment related to teachers' report of behavioral self
      control, cognitive self-control, and work habits in the spring of the
      kindergarten year. Classroom quality, particularly teachers' effective classroom
      management, was linked to children's greater behavioral and cognitive self
      control, children's higher behavioral engagement, and less time spent off-task in
      the classroom. Classroom quality did not moderate the relation between children's
      self-regulation upon school entry and children's adaptive classroom behaviors in
      kindergarten. The discussion considers the implications of classroom management
      for supporting children's early development of behavioral skills that are
      important in school settings.

PMID- 19586165
TI  - Source monitoring 15 years later: what have we learned from fMRI about the neural
      mechanisms of source memory?
AB  - Focusing primarily on functional magnetic resonance imaging (fMRI), this article
      reviews evidence regarding the roles of subregions of the medial temporal lobes,
      prefrontal cortex, posterior representational areas, and parietal cortex in
      source memory. In addition to evidence from standard episodic memory tasks
      assessing accuracy for neutral information, the article considers studies
      assessing the qualitative characteristics of memories, the encoding and
      remembering of emotional information, and false memories, as well as evidence
      from populations that show disrupted source memory (older adults, individuals
      with depression, posttraumatic stress disorder, or schizophrenia). Although there
      is still substantial work to be done, fMRI is advancing understanding of source
      memory and highlighting unresolved issues. A continued 2-way interaction between
      cognitive theory, as illustrated by the source monitoring framework (M. K.
      Johnson, S. Hashtroudi, & D. S. Lindsay, 1993), and evidence from cognitive
      neuroimaging studies should clarify conceptualization of cognitive processes
      (e.g., feature binding, retrieval, monitoring), prior knowledge (e.g., semantics,
      schemas), and specific features (e.g., perceptual and emotional information) and
      of how they combine to create true and false memories.

PMID- 19586174
TI  - School performance and genetic and environmental variance in antisocial behavior
      at the transition from adolescence to adulthood.
AB  - Antisocial behavior increases in adolescence, particularly among those who
      perform poorly in school. As adolescents move into adulthood, both educational
      attainment and the extent to which antisocial behavior continues have
      implications for adolescents' abilities to take on constructive social roles. The
      authors used a population-representative longitudinal twin study to explore how
      links among genetic and environmental influences at ages 17 and 24 may be
      implicated in the developmental processes involved. At age 17, expression of both
      genetic and nonshared environmental vulnerabilities unique to antisocial behavior
      was greater among those with low GPA than among those with higher GPA. This
      suggested that maintenance of high GPA buffered the impact of both genetic and
      environmental influences encouraging antisocial behavior. When GPA was high, both
      genetic and environmental influences involved in both traits encouraged good
      school performance and restrained antisocial behavior. At age 24, however,
      correlated family environmental influences drove the association between
      educational attainment and antisocial behavior. Antisocial characteristics
      involving school performance and educational attainment that transcend
      generations may slot individuals into social categories that restrict
      opportunities and reinforce antisocial characteristics.

PMID- 19586177
TI  - Depressive symptoms in mothers and children: preschool attachment as a moderator
      of risk.
AB  - Drawing from transactional models, the authors examined whether attachment
      security measured at age 3 (a potential source of differential vulnerability)
      interacts with the course of maternal depressive symptoms over an 8-year period
      (a potential source of differential exposure) in predicting children's self
      reported depressive symptoms at age 11. Participants were from the NICHD Study of
      Early Child Care (N = 938). Results from growth curve modeling and analysis of
      covariance suggest that preschool attachment quality moderates the influence of
      subsequent maternal depression on children. In particular, variability in the
      course of maternal depressive symptoms predicted offspring depressive symptoms
      only among those children with an insecure attachment history. A potential
      protective effect of early attachment security was evident among children exposed
      to the most chronic levels of maternal depression. Of the children with different
      patterns of insecure attachments, those with behaviors classified as disorganized
      appeared most vulnerable to also becoming depressed if paired with a mother
      experiencing ongoing depressive symptoms.

PMID- 19586176
TI  - Aggressive behavior between siblings and the development of externalizing
      problems: evidence from a genetically sensitive study.
AB  - This study investigated the prospective links between sibling aggression and the
      development of externalizing problems using a multilevel modeling approach with a
      genetically sensitive design. The sample consisted of 780 adolescents (390
      sibling pairs) who participated in 2 waves of the Nonshared Environment in
      Adolescent Development project. Sibling pairs with varying degree of genetic
      relatedness, including monozygotic twins, dizygotic twins, full siblings, half
      siblings, and genetically unrelated siblings, were included. The results showed
      that sibling aggression at Time 1 was significantly associated with the focal
      child's externalizing problems at Time 2 after accounting for the intraclass
      correlations between siblings. Sibling aggression remained significant in
      predicting subsequent externalizing problems even after controlling for the
      levels of preexisting externalizing problems and mothers' punitive parenting.
      This pattern of results was fairly robust across models with different
      informants. The findings provide converging evidence for the unique contribution
      of sibling aggression in understanding changes in externalizing problems during
      adolescence.

PMID- 19586178
TI  - Developmental and individual differences in young children's use and maintenance
      of a selective memory strategy.
AB  - Children who were 4 to 8 years of age were asked to perform a sort-recall task
      where only half of the items had to be studied and remembered. Following a
      baseline trial, children were assigned to 1 of 3 groups and were prompted to use
      either a sorting or a clustering strategy (experimental groups) or were not
      prompted at all (control group). Children were seen 2 weeks later and given a new
      set of items for the transfer-of-training sort-recall phases. Levels of recall
      and strategy use (sorting, clustering, multiple strategy use) were higher for
      older children, typical items, sorting prompts, and trials with repeated
      presentations of test materials. Older children used more strategies than younger
      children, although even 4-year-olds used more than one strategy when performing
      the memory tasks. Results of multivariate cluster analyses revealed systematic
      individual differences, separating low performers from production-deficient
      children and high performers. Overall, findings show that clustering appears to
      be an early developing, but less effective strategy, with multiple-strategy use
      and especially sorting being used more frequently and effectively by older
      children.

PMID- 19586175
TI  - Longitudinal relations of children's effortful control, impulsivity, and negative
      emotionality to their externalizing, internalizing, and co-occurring behavior
      problems.
AB  - The purpose of the study was to examine the relations of effortful control (EC),
      impulsivity, and negative emotionality to at least borderline clinical levels of
      symptoms and change in maladjustment over four years. Children's (N = 214; 77%
      European American; M age = 73 months) externalizing and internalizing symptoms
      were rated by parents and teachers at 3 times, 2 years apart (T1, T2, and T3) and
      were related to children's adult-rated EC, impulsivity, and emotion. In addition,
      the authors found patterns of change in maladjustment were related to these
      variables at T3 while controlling for the T1 predictor. Externalizing problems
      (pure or co-occurring with internalizing problems) were associated with low EC,
      high impulsivity, and negative emotionality, especially anger, and patterns of
      change also related to these variables. Internalizing problems were associated
      with low impulsivity and sadness and somewhat with high anger. Low attentional EC
      was related to internalizing problems only in regard to change in maladjustment.
      Change in impulsivity was associated with change in internalizing primarily when
      controlling for change in externalizing problems.

PMID- 19586179
TI  - Predictors and pathways from infancy to symptoms of anxiety and depression in
      early adolescence.
AB  - Data from a prospective 11-year longitudinal survey were used to identify early
      predictors and pathways to symptoms of anxiety and depression at 12-13 years of
      age, and to examine whether there were unique predictors of anxious versus
      depressive symptoms. Structural equation modeling was used to explore
      longitudinal relations between contextual (maternal distress, family adversities,
      and social support) and temperamental (shyness and emotionality) risk factors in
      their prediction of informant-consistent symptoms of anxiety and depression. The
      results show that early risk factors can explain 38% of the variance in boys'
      covarying symptoms of anxiety and depression in early adolescence, and 25% of
      variance in girls' covarying symptoms. Two main pathways were identified. One
      pathway was through temperament, as nearly all risk factors were partly mediated
      through child emotionality in midchildhood. Another pathway was through early
      contextual risk factors, with all direct and indirect contextual impact from
      before 5 years of age. Family adversity uniquely predicted depressive symptoms.
      These findings underscore the persisting impact of contextual predictors in
      families with children less than 5 years of age. The importance of early
      interventions to prevent adolescent internalizing problems is stressed.

PMID- 19586180
TI  - Family-school connections and the transitions of low-income youths and English
      language learners from middle school to high school.
AB  - The theoretical and policy focus on parental involvement in education has evolved
      into a consideration of 2-way connections between families and schools. Working
      from a social capital perspective emphasizing the importance of information in
      periods and domains of uncertainty, the author tested a specific application of
      this reconceptualization in this study. Multilevel models of the National
      Education Longitudinal Study (n = 17,899) revealed that youths started high
      school in higher level math when parents, middle school personnel, and high
      school personnel were in contact with each other and when middle school personnel
      bridged middle school and high school. The observed effects of other family
      school patterns on math and of all family-school patterns on science were driven
      by selection, including the personal characteristics that select adolescents into
      different family-school configurations. Multiple forms of family-school
      communication were related to reduced income and language disparities in math and
      science coursework, regardless of their associations with coursework in the
      general population.

PMID- 19586181
TI  - Anxious solitude and peer exclusion predict social helplessness, upset affect,
      and vagal regulation in response to behavioral rejection by a friend.
AB  - It was hypothesized that combined individual child vulnerability (anxious
      solitude) and interpersonal stress (peer exclusion) would predict the strongest
      responses to experimentally manipulated behavioral peer rejection. Results
      indicated that in a sample of 3rd graders (N = 160, 59% girls), anxious solitary
      excluded children displayed more behavioral manifestations of social helplessness
      before and after behavioral rejection, reported more feelings of rejection in
      anticipation of and reaction to behavioral rejection, and were observably more
      upset during behavioral rejection than were normative children. Moreover,
      affective responses to behavioral rejection mediated the relation between anxious
      solitary excluded status and behavioral manifestations of social helplessness.
      Furthermore, anxious solitary excluded children versus anxious solitary children
      demonstrated excessive suppression of vagal tone and more sustained acceleration
      in heart rate during the experiment. Results also indicated that affective,
      social-cognitive, and regulatory processes directly contributed to children's
      responses to behavioral rejection.

PMID- 19586182
TI  - Differentiation of cognitive abilities across the life span.
AB  - Existing representations of cognitive ability structure are exclusively based on
      linear patterns of interrelations. However, a number of developmental and
      cognitive theories predict that abilities are differentially related across ages
      (age differentiation-dedifferentiation) and across levels of functioning (ability
      differentiation). Nonlinear factor analytic models were applied to multivariate
      cognitive ability data from 6,273 individuals, ages 4 to 101 years, who were
      selected to be nationally representative of the U.S. population. Results
      consistently supported ability differentiation but were less clear with respect
      to age differentiation-dedifferentiation. Little evidence for age modification of
      ability differentiation was found. These findings are particularly informative
      about the nature of individual differences in cognition and about the
      developmental course of cognitive ability level and structure.

PMID- 19586183
TI  - The emotional and academic consequences of parental conditional regard: comparing
      conditional positive regard, conditional negative regard, and autonomy support as
      parenting practices.
AB  - The authors conducted 2 studies of 9th-grade Israeli adolescents (169 in Study 1,
      156 in Study 2) to compare the parenting practices of conditional positive
      regard, conditional negative regard, and autonomy support using data from
      multiple reporters. Two socialization domains were studied: emotion control and
      academics. Results were consistent with the self-determination theory model of
      internalization, which posits that (a) conditional negative regard predicts
      feelings of resentment toward parents, which then predict dysregulation of
      negative emotions and academic disengagement; (b) conditional positive regard
      predicts feelings of internal compulsion, which then predict suppressive
      regulation of negative emotions and grade-focused academic engagement; and (c)
      autonomy support predicts sense of choice, which then predicts integrated
      regulation of negative emotions and interest-focused academic engagement. These
      findings suggest that even parents' use of conditional positive regard as a
      socialization practice has adverse emotional and academic consequences, relative
      to autonomy support.

PMID- 19586184
TI  - Infants' intermodal perception of canine (Canis familairis) facial expressions
      and vocalizations.
AB  - From birth, human infants are able to perceive a wide range of intersensory
      relationships. The current experiment examined whether infants between 6 months
      and 24 months old perceive the intermodal relationship between aggressive and
      nonaggressive canine vocalizations (i.e., barks) and appropriate canine facial
      expressions. Infants simultaneously viewed static aggressive and nonaggressive
      expressions of the same canine and heard an aggressive or nonaggressive bark.
      Results indicate that 6-month-olds perceived the intermodal relationship for
      aggressive and nonaggressive barks and the appropriate expression. Results also
      revealed that in older but not younger infants, the initial or first looks were
      directed toward the appropriate expression and that older infants also looked
      proportionately longer to the incongruent expression during the latter half of
      the test trials. Findings are discussed in terms of perceptual narrowing and the
      effects of familiarity and experience.

PMID- 19586185
TI  - Do gender differences in help avoidance vary by ethnicity? An examination of
      African American and European American students during early adolescence.
AB  - The present research examined whether the nature of gender differences varies by
      race for two types of academic engagement in the classroom (help avoidance and
      voice with the teacher) in a sample of early adolescents (N = 456; 55% female,
      60% African American and 40% European American) making the transition to middle
      school. Growth curve analyses indicated that help avoidance increased over time,
      voice remained stable, and achievement declined. In line with hypotheses based on
      cultural variations in the female role, there were no gender differences in help
      avoidance for African American students, whereas for European American students,
      girls were lower in help avoidance than were boys. For African American students,
      there were no gender differences in voice with the teacher, whereas for European
      American students, girls were higher than were boys. These group differences were
      present at all 3 waves. For all students, increases in help avoidance negatively
      predicted changes in achievement, whereas increases in voice positively predicted
      achievement. Results underscore the importance of examining gender and ethnicity
      together to understand academic adjustment during early adolescence.

PMID- 19586186
TI  - Aggressive versus nonaggressive antisocial behavior: distinctive etiological
      moderation by age.
AB  - Research has supported the existence of distinct behavioral patterns, demographic
      correlates, and etiologic mechanisms for aggressive (AGG) versus nonaggressive
      but delinquent (DEL) antisocial behavior. Though behavioral genetic studies have
      the potential to further crystallize these dimensions, inconsistent results have
      limited their contribution. These inconsistencies may stem in part from the
      limited attention paid to the impact of age. In the current study, the authors
      thus examined age-related etiological moderation of AGG and DEL antisocial
      behavior in a sample of 720 sibling pairs (ranging in age from 10 to 18 years)
      with varying degrees of genetic relatedness. Results reveal that the magnitude of
      genetic and environmental influences on AGG remained stable across adolescence.
      By contrast, genetic influences on DEL increased dramatically with age, whereas
      shared environmental influences decreased. Subsequent longitudinal analyses fully
      replicated these results. Such findings highlight etiological distinctions
      between aggression and delinquency, and offer insights into the expression of
      genetic influences during development.

PMID- 19586187
TI  - Daily family assistance and the psychological well-being of adolescents from
      Latin American, Asian, and European backgrounds.
AB  - The daily diary method was used to examine the implications of adolescents' daily
      assistance behaviors for both positive and negative aspects of psychological well
      being among an ethnically diverse sample of 752 adolescents of ages 14 to 15
      years. Results indicated that, contrary to the expectations of some observers,
      providing daily assistance to the family generally was not stressful for
      adolescents. Rather, assisting the family was associated with higher levels of
      happiness due, in large part, to the sense of role fulfillment it provided the
      adolescents. Few individual or group differences were observed in the association
      between family assistance and psychological well-being. These results suggest
      that family assistance serves as a meaningful activity in adolescents' lives by
      creating a sense of connection to the family.

PMID- 19586188
TI  - Action type and goal type modulate goal-directed gaze shifts in 14-month-old
      infants.
AB  - Ten- and 14-month-old infants' gaze was recorded as the infants observed videos
      of different hand actions directed toward multiple goals. Infants observed an
      actor who (a) reached for objects and displaced them, (b) reached for objects and
      placed them inside containers, or (c) moved his fisted hand. Fourteen-month-olds,
      but not 10-month-olds, anticipated the goal of reaching actions but tracked all
      the other actions reactively. Fourteen-month-olds also produced more anticipatory
      gaze shifts during containment compared with displacement and differentiated
      between reaching actions dependent on whether the overall goal was to displace
      objects or place objects inside containers. These results demonstrate that action
      type and goal type modulate the latency of goal-directed gaze shifts in infants.

PMID- 19586189
TI  - Use of missing data methods in longitudinal studies: the persistence of bad
      practices in developmental psychology.
AB  - Developmental science rests on describing, explaining, and optimizing
      intraindividual changes and, hence, empirically requires longitudinal research.
      Problems of missing data arise in most longitudinal studies, thus creating
      challenges for interpreting the substance and structure of intraindividual
      change. Using a sample of reports of longitudinal studies obtained from three
      flagship developmental journals-Child Development, Developmental Psychology, and
      Journal of Research on Adolescence-we examined the number of longitudinal studies
      reporting missing data and the missing data techniques used. Of the 100
      longitudinal studies sampled, 57 either reported having missing data or had
      discrepancies in sample sizes reported for different analyses. The majority of
      these studies (82%) used missing data techniques that are statistically
      problematic (either listwise deletion or pairwise deletion) and not among the
      methods recommended by statisticians (i.e., the direct maximum likelihood method
      and the multiple imputation method). Implications of these results for
      developmental theory and application, and the need for understanding the
      consequences of using statistically inappropriate missing data techniques with
      actual longitudinal data sets, are discussed.

PMID- 19586190
TI  - Understanding immigrant families from around the world: introduction to the
      special issue.
AB  - Investigations of immigrant families enable researchers to trace family processes
      and children's psychological adjustment in the presence of trenchant
      sociocultural change, cultural conflict, family dislocation, and the need for
      readjustment to new social environments. This special issue of 15 articles
      presents psychosocial research on immigrant families and children residing in
      Canada, Germany, Israel, the Netherlands, Portugal, and the United States. The
      articles focus on the psychosocial adaptation of immigrant families, parenting
      practices and their implications for child outcomes, and the importance of parent
      adolescent relationships for adolescent mental health. Most of the articles are
      based on quantitative research methodologies. It is concluded that research on
      immigrant families is well suited to advance knowledge about the mutual
      dependence of dynamic sociocultural and family processes.

PMID- 19586191
TI  - Family economic stress and academic well-being among Chinese-American youth: the
      influence of adolescents' perceptions of economic strain.
AB  - This study examined the pathways by which family economic stress influenced
      youth's educational outcomes in a sample of 444 Chinese American adolescents (M
      ages = 13.0, 17.1 years at waves 1 and 2, respectively). Using latent variable
      structural equation modeling, results across two waves of data, spanning early to
      late adolescence, demonstrated that the influence of parent report of economic
      stress on youth academic achievement (i.e., GPA), school engagement, and positive
      attitudes about education was mediated through youth's perceptions of family
      economic strain and self-reports of depressive symptoms. These relationships were
      observed to remain significant after accounting for selection bias using
      individual fixed-effects models. Finally, youth's perceptions of family economic
      strain were found to more strongly predict depressive symptoms during later, as
      compared to earlier, adolescence; all other modeled relationships were equivalent
      across the two time periods. Implications for expanding theoretical tenets of the
      Family Economic Stress Model are discussed.

PMID- 19586192
TI  - Intergenerational family solidarity: value differences between immigrant groups
      and generations.
AB  - Although immigrants may be more dependent on their immediate family for support,
      they may also experience a wider generation-gap in values regarding
      intergenerational solidarity, because of processes of acculturation. Based on
      large scale survey data (N = 2,028), differences between first and second
      generation immigrants in values regarding intergenerational solidarity were
      examined among family members in the Netherlands with an immigration background
      from Turkey, Morocco, Suriname, and The Dutch Antilles. Using a multilevel
      analytic approach, effects of family and individual characteristics on values
      regarding intergenerational solidarity were tested, considering the perspectives
      of two generations. It was found that immigrants with Moroccan and Turkish
      backgrounds scored higher on values with respect to intergenerational family
      solidarity than immigrants stemming from Suriname and The Antilles. First
      generation immigrants placed higher values on family solidarity compared to
      second generation immigrants. Additionally, religious denomination was a
      significant predictor of higher values with respect to intergenerational family
      solidarity. Immigration and acculturation may create great strains in migrant
      families. Policies to support the fabric of intergenerational solidarity should
      consider ethnic and religious background and immigration history.

PMID- 19586193
TI  - Friendship homophily among ethnic German immigrants: a longitudinal comparison
      between recent and more experienced immigrant adolescents.
AB  - Immigrant adolescents have been found to show high levels of friendship homophily
      (the tendency to prefer intra-ethnic over interethnic friends). Based on
      acculturation theories, we predicted longitudinal changes and interindividual
      differences in level and rate of change in friendship homophily by immigrant
      composition of school, parental objections to the cultural adaptation of their
      offspring, discrimination, and language use. Altogether 218 newcomer and 272
      experienced adolescents who had emigrated from the former Soviet Union to Germany
      participated in 4 annual assessments. Friendship homophily was assessed by
      percentage of intra-ethnic friends. Results revealed higher levels of friendship
      homophily among newcomer (75%) than among experienced (65%) adolescents at Time
      1, and a significant decrease over time was found only among newcomers. Higher
      age, higher percentage of immigrants at school, and lower levels of new language
      use all related to higher friendship homophily. Rate of change in friendship
      homophily was strongly related to change in new language use. Findings suggest
      that friendship formation with native adolescents is related to social learning
      processes, in which new language use plays a crucial role.

PMID- 19586195
TI  - Relations among parental acceptance and control and children's social adjustment
      in Chinese American and European American families.
AB  - Parental acceptance and control are the 2 dimensions of parenting that have been
      investigated most; however, little is known about their cross-cultural
      expressions. This longitudinal study examined acceptance, control, and R. Chao's
      indigenous Chinese notion of control--chiao shun (training)--in 35 immigrant
      Chinese American (CA) and 38 European American (EA) families. Data were collected
      when children were in preschool and kindergarten (T1); first and second grades
      (T2); and third and fourth grades (T3). Within couples, CA mothers and fathers
      reported similar levels of acceptance and control, whereas EA mothers and fathers
      did not. CA fathers' and mothers' and EA mothers' acceptance and control exerted
      a positive influence on their children's psychological adjustment. CA fathers'
      training negatively predicted their children's problem behaviors 4 years later.

PMID- 19586194
TI  - Authoritative parenting among immigrant Chinese mothers of preschoolers.
AB  - The goals of this study were: (a) to examine authoritative parenting style among
      Chinese immigrant mothers of young children, (b) to test the mediational
      mechanism between authoritative parenting style and children's outcomes; and (c)
      to evaluate 3 predictors of authoritative parenting style (psychological well
      being, perceived support in the parenting role, parenting stress). Participants
      included 85 Chinese immigrant mothers and their preschool children. Mothers
      reported on their parenting style, psychological well-being, perceived parenting
      support and stress, and children's hyperactivity/attention. Teacher ratings of
      child adjustment were also obtained. Results revealed that Chinese immigrant
      mothers of preschoolers strongly endorsed the authoritative parenting style.
      Moreover, authoritative parenting predicted increased children's
      behavioral/attention regulation abilities (lower hyperactivity/inattention),
      which then predicted decreased teacher rated child difficulties. Finally, mothers
      with greater psychological well-being or parenting support engaged in more
      authoritative parenting, but only under conditions of low parenting stress.
      Neither well-being nor parenting support predicted authoritative parenting when
      parenting hassles were high. Findings were discussed in light of cultural- and
      immigration-related issues facing immigrant Chinese mothers of young children.

PMID- 19586196
TI  - Do we see eye to eye? Chinese mothers' and fathers' parenting beliefs and values
      for toddlers in Canada and China.
AB  - This study explores maternal and paternal parenting practices (authoritative or
      authoritarian) and parental values and goals for toddlers among Chinese mothers
      and fathers in Canada and China. The participants included 126 families of 1-year
      old toddlers (67 Chinese Canadians and 59 mainland Chinese). The findings
      revealed that Chinese Canadian parents were more supportive of authoritative
      practices, and Chinese parents were more likely to support authoritarian
      practices. Between mothers and fathers, gender differences were found within
      countries. Interparental agreement for parenting beliefs varied by infant gender
      and country. For parental values, parents generally endorsed self-confidence as
      the most important trait for their toddlers. Endorsement of other traits
      (collectivistic and individualistic) varied in importance. Links among parenting
      beliefs and desired personality traits for their children were also explored.

PMID- 19586197
TI  - Interpretations of parental control by Asian immigrant and European American
      youth.
AB  - Although studies have reported ethnic and cultural differences in the effects of
      parenting on adolescent well-being, rarely have they included specific
      examinations of the cultural processes underlying these differences. This study
      examined adolescents' affective interpretations of parents' control (i.e.,
      feelings of anger toward control) and how these interpretations may moderate the
      relationship between control and adolescents' behavioral adjustment. The study
      comprised 1,085 immigrant youth of Chinese, Korean, and Filipino descent, and
      also European American youth from high schools in the greater Los Angeles area.
      Differences were found between European American and Asian immigrant youth in the
      effects of both behavioral control and psychological control. Furthermore, among
      European Americans only, as adolescents' feelings of anger increased, the
      beneficial consequences of behavioral control decreased, whereas the negative
      effects of psychological control on behavior problems decreased. The results
      suggest that feeling anger toward parents' use of psychological control may serve
      a protective function for European American youth but not for Asian immigrant
      youth. In contrast, feeling angry about behavioral control seems to reduce the
      beneficial consequences of control among European Americans but not Asian
      immigrants.

PMID- 19586198
TI  - Child and mother play in three U.S. cultural groups: comparisons and
      associations.
AB  - Child and mother play (n = 113 20-month-olds) among South American Latino
      immigrants, Japanese immigrants, and European Americans in the United States was
      investigated. Culturally universal patterns of play dominated the findings. For
      example, no cultural differences in the prevalence of exploratory or symbolic
      play were found for either children or their mothers. Regardless of their
      culture, boys engaged in significantly more exploratory and less symbolic play
      than did girls when they played by themselves. Few relations were found between
      child play in the two play sessions. Across cultural groups, children's
      exploratory play was significantly positively related to both maternal
      demonstrations and solicitations of exploratory play. The results identify which
      realms of child growth, parenting, and family function call for special attention
      and cultural sensitivity, as well as which do not, in the dynamics of immigrant
      families.

PMID- 19586199
TI  - How much do I tell thee? Strategies for managing information to parents among
      American adolescents from Chinese, Mexican, and European backgrounds.
AB  - Strategies for managing information about activities to parents, including
      partial disclosure, avoidance, lying, and full disclosure, were examined in 479
      American adolescents (M = 16.38 years, SD = 0.77) varying in generational status
      and from Mexican, Chinese, and European backgrounds. Information management
      strategies for personal, prudential, and overlapping (multifaceted) activities as
      defined within social domain theory were examined. With age, parental education,
      and generational status controlled, Chinese American adolescents partially
      disclosed more to mothers about personal and multifaceted activities than did
      Mexican American adolescents and more to fathers about personal activities than
      did European American teens. In contrast, European and Mexican American
      adolescents fully disclosed more to mothers about personal activities than did
      Chinese-origin adolescents. Strategies varied by generation among Chinese
      American youth; second-generation adolescents avoided discussing activities with
      parents more than did immigrants. Adolescents who fully disclosed about all
      activities and lied less about multifaceted and personal activities reported
      stronger endorsement of obligations to assist their families, more trust in
      parents, and less problem behavior. More depressed mood was associated with more
      lying about personal activities.

PMID- 19586200
TI  - Predictors of mental health among adolescents from immigrant families in
      Portugal.
AB  - The aims of this study were to investigate the degree of mental health problems
      among adolescents with immigrant background in Portugal and the factors that may
      predict mental health problems. The study sample consisted of 755 immigrant
      adolescents from seven ethnocultural groups (Cape Verdeans, Angolans, Indians,
      Mozambicans, East Timorese, Sao Tomese, and Guineans) and 320 native Portuguese
      adolescents. Generally, most respondents did not report major psychological
      adjustment problems. Adolescents from immigrant families reported fewer mental
      health problems than their native Portuguese counterparts, and girls reported
      more mental health problems than did boys. Predictive factors-sociodemographic,
      intercultural contact, and psychosocial adjustment variables-were significantly
      linked to youths' mental health. Major predictors of poor psychological
      adjustment were perceived discrimination, social difficulties, and behavioral
      problems. As expected, different factors explained the psychological adaptation
      of adolescents by gender. Implications of the study for counselors are discussed.

PMID- 19586201
TI  - The experiences of Sudanese unaccompanied minors in foster care.
AB  - Sudanese unaccompanied minors were separated from their parents in childhood and
      lived apart from their families in refugee camps for close to a decade before
      being resettled in the United States. This phenomenological study examines the
      refugees' experiences of living in American foster families after living in peer
      groups in the camps. Interviews with 18 young adults, 7 years after resettlement,
      revealed that nearly all of the youth struggled with parental authority
      initially, and nearly half of them changed placements because of relationship
      difficulties with their foster parents. Misunderstandings based on cultural
      differences often exacerbated conflicts. However, 15 of 18 youth currently had a
      positive relationship with at least 1 foster parent, sometimes with a parent from
      their second or third placement. Changing foster families is often considered a
      failure in the child welfare system, but several Sudanese youth reported that
      having supportive relationships helped them during the acculturation process
      whether those relationships developed during the first or last placement.

PMID- 19586202
TI  - A longitudinal study of family obligation and depressive symptoms among Chinese
      American adolescents.
AB  - The purpose of this 2-year, 3-wave longitudinal study of Chinese American
      adolescents was to examine how family obligation behaviors and attitudes change
      over time; how gender, nativity, and birth order predict these trajectories; and
      whether family obligation relates to depressive symptoms. Findings suggest that
      family obligation behaviors decreased over the 2-year period but that family
      obligation attitudes were stable. Moreover, foreign-born adolescents reported
      higher levels of family obligation behavior than U.S.-born adolescents, and
      firstborn adolescents reported higher family obligation attitudes than laterborn
      adolescents. There were no gender differences in family obligation behaviors or
      attitudes. The findings also suggest that initial higher levels of family
      obligation were associated with subsequently fewer depressive symptoms. Finally,
      changes in family obligation behaviors related to changes in depressive symptoms
      over time such that increasing family obligation behaviors related to decreasing
      depressive symptoms. The results highlight the importance of understanding the
      role of family obligation to Chinese American adolescents' mental health.

PMID- 19586203
TI  - Parent-child role reversal and psychological adjustment among immigrant youth in
      Israel.
AB  - Parent-child role reversal and its relation to psychological adjustment was
      investigated in Israel among immigrants from the former Soviet Union. Study 1
      examined immigrant and Israeli-born college students (n = 184), and Study 2
      examined adolescents (n = 180) by means of self-report questionnaires. Two major
      factors of role reversal emerged: child dominance and family support. The results
      of both studies clearly showed that immigrants assume more dominant roles and
      parental responsibilities in their families and receive less support from their
      parents than their Israeli-born peers. Role reversal dimensions had differential
      relations with adjustment. Child dominance was mostly not related to adjustment,
      except for a positive correlation with psychological distress among immigrants.
      Familial support appeared to be the most important factor related to better
      adjustment among all studied groups, immigrants included. It is interesting that
      language brokering (i.e., translating for parents), although associated with
      child dominance, was negatively related to self-perceptions. Possible
      explanations within the Israeli context are suggested for negative language
      brokering correlates, with support from the interviews conducted among the
      immigrants.

PMID- 19586204
TI  - Parenting and psychological adjustment of adolescent immigrants in Israel.
AB  - Parental and familial factors and their association with adolescents' mental
      health were examined among former Soviet Union (FSU) immigrants and nonimmigrants
      in Israel. Questionnaires regarding parental control, inconsistency, and
      rejection, in addition to adolescent-family connectedness and psychological
      disorders, were administered to 83 FSU immigrants and 106 nonimmigrant
      adolescents. According to the results, FSU adolescents are less connected to
      their families, experience their parents as less warm and more inconsistent in
      their childrearing behavior, report that their mothers subject them to a higher
      level of control, and the psychological disorders among them are more widespread
      than among nonimmigrant adolescents. Maternal control, maternal temporal
      inconsistency, and maternal and paternal rejection were associated with
      psychological disorders only among nonimmigrant adolescents. No such association
      was found among FSU adolescents, suggesting that FSU mental health problems are
      associated with immigration and cultural and social factors, rather than parental
      and familial factors. A comprehensive intervention program is required to provide
      support and assistance to help immigrants overcome their psychological
      distresses.

PMID- 19586205
TI  - Parent-child acculturation, parenting, and adolescent depressive symptoms in
      Chinese immigrant families.
AB  - Using a sample of 388 father-adolescent and 399 mother-adolescent dyads in
      Chinese immigrant families, the current investigation tested Portes and Rumbaut's
      (1996) assertion that generational dissonance may indicate a family context that
      places children at increased risk for adverse outcomes. Study findings suggest
      that a high discrepancy in father-adolescent acculturation levels relates
      significantly to more adolescent depressive symptoms. The study further
      demonstrates that the quality of the parenting relationship between fathers and
      adolescents operates as a mediator between father-adolescent acculturation
      discrepancy and adolescent depressive symptoms. Specifically, a high level of
      discrepancy in American orientation between fathers and adolescents is associated
      with unsupportive parenting practices, which, in turn, are linked to more
      adolescent depressive symptoms. These relationships are significant even after
      controlling for the influence of family socioeconomic status and parents' and
      adolescents' sense of discrimination within the larger society.

PMID- 19586206
TI  - Cognitive functioning in Alzheimer's and vascular dementia: a meta-analysis.
AB  - Differentiating between Alzheimer's disease (AD) and vascular dementia (VaD)
      remains difficult but important if existing pharmacological treatments are to
      provide symptomatic relief in the case of AD or to alter disease progression in
      the case of VaD. Cognitive assessments play an important role in aiding
      diagnosis, despite a lack of clear evidence defining the cognitive abilities and
      tests that best distinguish between the two types of dementia. The current study
      therefore completed a meta-analysis of research comparing the cognitive abilities
      of persons diagnosed with AD and VaD. A comprehensive search was undertaken of
      the PubMed and PsychInfo databases, with 81 studies being eligible for inclusion.
      Weighted Cohen's d effect sizes, percentage overlap statistics, fail-safe Ns, and
      confidence intervals were calculated for all cognitive tests. Of the tests that
      were examined by more than one study, there was one test of perception and one
      test of verbal memory that showed large and significant group differences. There
      were an additional 12 tests that may prove useful. However, all cognitive tests
      were limited in their ability to discriminate between AD and VaD, suggesting that
      they should be used cautiously and only in conjunction with other information
      (imaging, medical history) when diagnosing patients.

PMID- 19586207
TI  - Factors contributing to attentional impairments after traumatic brain injury.
AB  - The aim of the present study was to investigate the contribution of impaired
      information processing speed and strategic control of attention to performance on
      attentional tasks after traumatic brain injury (TBI). Forty moderately to
      severely injured rehabilitation inpatients and 40 healthy controls completed a
      selection of attentional tasks. Slowed processing speed in the TBI group was
      identified on the Symbol Digit Modalities Test (SDMT), 2&7 Selective Attention
      Test (2&7), Selective Attention (SAT), and Four Choice Reaction Time (4CRT)
      tasks. Impaired working memory was evident on the Letter Number Sequencing (LNS)
      task. Structural equation modeling revealed that the group difference in RT on
      the complex SAT was accounted for by slowed speed of processing on the simple
      SAT, and not working memory. TBI participants made more errors and missed
      responses on the complex version of the SAT, suggesting impairment in some
      aspects of strategic control of attention, and appeared unable to benefit from
      the automatic condition of the 2&7 Test. There was little evidence of deficit on
      the Sustained Attention to Response Task (SART). The present study provides
      evidence for a significant contribution of slowed processing speed to impaired
      performance on attentional tasks after TBI.

PMID- 19586208
TI  - Double jeopardy! The additive consequences of negative affect on performance
      monitoring decrements following traumatic brain injury.
AB  - Survivors of severe traumatic brain injury (TBI) are at increased risk for
      emotional sequelae. The current study utilized the error-related negativity (ERN)
      and posterror positivity (Pe) components of the event-related potential (ERP) to
      test the hypothesis that negative affect disproportionately impairs performance
      monitoring following severe TBI. High-density ERPs were acquired while 20
      survivors of severe TBI and 20 demographically matched controls performed a
      single-trial Stroop task. Response-locked ERPs were separately averaged for
      correct and error trials. Negative affect was measured as the single latent
      factor of measures of depression and anxiety. Groups did not differ on overall
      level of negative affect. Control and TBI participants did not differ on error
      rates as a function of negative affect, but differed in response times. ERP
      results revealed disproportionately smaller ERN amplitudes in participants with
      TBI relative to controls as a function of negative affect. Pe amplitude did not
      differ between groups. Negative affect inversely correlated with ERN amplitude in
      TBI but not control participants. Overall, results support a "double jeopardy"
      hypothesis of disproportionate impairments in performance monitoring when
      negative affect is overlaid on severe TBI.

PMID- 19586210
TI  - Growth mixture modeling of academic achievement in children of varying birth
      weight risk.
AB  - The extremes of birth weight and preterm birth are known to result in a host of
      adverse outcomes, yet studies to date largely have used cross-sectional designs
      and variable-centered methods to understand long-term sequelae. Growth mixture
      modeling (GMM) that utilizes an integrated person- and variable-centered approach
      was applied to identify latent classes of achievement from a cohort of school-age
      children born at varying birth weights. GMM analyses revealed 2 latent
      achievement classes for calculation, problem-solving, and decoding abilities. The
      classes differed substantively and persistently in proficiency and in growth
      trajectories. Birth weight was a robust predictor of class membership for the 2
      mathematics achievement outcomes and a marginal predictor of class membership for
      decoding. Neither visuospatial-motor skills nor environmental risk at study entry
      added to class prediction for any of the achievement skills. Among children born
      preterm, neonatal medical variables predicted class membership uniquely beyond
      birth weight. More generally, GMM is useful in revealing coherence in the
      developmental patterns of academic achievement in children of varying weight at
      birth and is well suited to investigations of sources of heterogeneity.

PMID- 19586209
TI  - Incidental and intentional sequence learning in youth-onset psychosis and
      Attention-Deficit/Hyperactivity Disorder (ADHD).
AB  - The goal was to compare incidental and intentional spatial sequence learning in
      youth-onset psychosis and ADHD. The authors tested 8- to 19-year-olds with
      psychosis or ADHD and healthy controls on a serial reaction time (RT) task and
      used manual and oculomotor measures to examine learning. Participants were also
      administered a block in which they were explicitly instructed to learn a
      sequence. As in our previous studies with healthy adults and children, oculomotor
      anticipations and RTs showed learning effects similar to those in the manual
      modality. Results showed intact sequence-specific learning but fewer oculomotor
      anticipations in both clinical groups during incidental learning. In intentional
      learning, only the psychosis group showed impairments compared to controls. There
      were no interactions between age and diagnosis. Thus, the psychosis group showed
      relatively preserved incidental learning despite impairments in intentional
      learning. Additionally, both clinical groups showed impairments in the ability to
      search for, extract, and anticipate regularities (whether the regularities were
      there or not), but not in the ability to respond to these regularities when they
      were there.

PMID- 19586214
TI  - Effects of sex hormone therapy on interhemispheric crosstalk in postmenopausal
      women.
AB  - Evidence exists that fluctuating levels of sex hormones affect interhemispheric
      interaction in women during the menstrual cycle. The present study investigated
      whether interhemispheric interaction is susceptible to direct hormonal
      manipulations via hormone therapy (HT). Sixty-eight postmenopausal women who
      received HT either with estrogen alone (n = 15), an estrogen-gestagen combination
      (n = 22) or without HT (n = 31) were investigated. Participants were asked to
      match letters according to their physical or name identity. Matches were
      presented either within or across visual half-fields. Additionally, a simple
      reaction time task, assumed to estimate interhemispheric transfer time (IHTT),
      was used. Overall, postmenopausal women showed an across-field advantage in the
      more demanding name-identity task but not in the less demanding physical-identity
      task. However, across both tasks, the groups differed in responses to within- and
      across-field trials: the control group performed better on across- than within
      field trials, whereas both HT groups showed faster responses on within- than
      across-field trials. IHTT did not differ between groups. The findings suggest
      that postmenopausal estrogen-therapy affects the relative efficiency of
      interhemispheric integration by modulating within-hemisphere functioning.

PMID- 19586213
TI  - Different cognitive profiles for single compared with recurrent fallers without
      dementia.
AB  - Relationships between self-reported retrospective falls and cognitive measures
      (executive function, reaction time [RT], processing speed, working memory, visual
      attention) were examined in a population based sample of older adults (n = 658).
      Two of the choice RT tests involved inhibiting responses to either targets of a
      specific color or location with hand and foot responses. Potentially confounding
      demographic variables, medical conditions, and postural sway were controlled for
      in logistic regression models, excluding participants with possible cognitive
      impairment. A factor analysis of cognitive measures extracted factors measuring
      RT, accuracy and inhibition, and visual search. Single fallers did not differ
      from nonfallers in terms of health, sway or cognitive function, except that they
      performed worse on accuracy and inhibition. In contrast, recurrent fallers
      performed worse than nonfallers on all measures. Results suggest that occasional
      falls in late life may be associated with subtle age-related changes in the
      prefrontal cortex leading to failures of executive control, whereas recurrent
      falling may result from more advanced brain ageing that is associated with
      generalized cognitive decline.

PMID- 19586212
TI  - Comprehension of concrete and abstract words in semantic dementia.
AB  - The vast majority of brain-injured patients with semantic impairment have better
      comprehension of concrete than abstract words. In contrast, several patients with
      semantic dementia (SD), who show circumscribed atrophy of the anterior temporal
      lobes bilaterally, have been reported to show reverse imageability effects, that
      is, relative preservation of abstract knowledge. Although these reports largely
      concern individual patients, some researchers have recently proposed that
      superior comprehension of abstract concepts is a characteristic feature of SD.
      This would imply that the anterior temporal lobes are particularly crucial for
      processing sensory aspects of semantic knowledge, which are associated with
      concrete not abstract concepts. However, functional neuroimaging studies of
      healthy participants do not unequivocally predict reverse imageability effects in
      SD because the temporal poles sometimes show greater activation for more abstract
      concepts. The authors examined a case-series of 11 SD patients on a synonym
      judgment test that orthogonally varied the frequency and imageability of the
      items. All patients had higher success rates for more imageable as well as more
      frequent words, suggesting that (1) the anterior temporal lobes underpin semantic
      knowledge for both concrete and abstract concepts, (2) more imageable items-
      perhaps because of their richer multimodal representations--are typically more
      robust in the face of global semantic degradation and (3) reverse imageability
      effects are not a characteristic feature of SD.

PMID- 19586215
TI  - Assessment of unilateral spatial neglect: scoring star cancellation performance
      from video recordings--method, reliability, benefits, and normative data.
AB  - Unilateral spatial neglect, a debilitating condition affecting awareness of one
      side of space, is commonly assessed using cancellation tasks in which patients
      cross out targets distributed over a sheet. Standard scores emphasize the left
      right distribution of omissions. Here, the additional value of extracting
      temporal as well as spatial aspects of performance from video recordings was
      examined. Videos from 18 patients with left neglect and 19 healthy age-matched
      control participants were obtained. Interrater reliability of the video analysis
      was high. In addition to overall differences in target detection and bias,
      patients significantly differed from the control group in terms of the location
      of first cancellation, overall slowness, greater variability in speed, systematic
      slowing with time on task and as a function of target location, less coherent
      search organization, and a sharply increased tendency to recancel targets.
      Considering a subset of patients whose scores, by standard criteria, were at or
      near the normal range indicated that these additional variables indeed increased
      the sensitivity of the task as well as allowed the simultaneous assessment of
      spatial and nonspatial aspects of the disorder.

PMID- 19586211
TI  - Neuroanatomical and cognitive mediators of age-related differences in perceptual
      priming and learning.
AB  - Our objectives were to assess age differences in perceptual repetition priming
      and perceptual skill learning and to determine whether they are mediated by
      cognitive resources and regional cerebral volume differences. Fragmented picture
      identification paradigm allows the study of both priming and learning within the
      same task. The authors presented this task to 169 adults (ages 18-80), assessed
      working memory and fluid intelligence, and measured brain volumes of regions that
      were deemed relevant to those cognitive skills. The data were analyzed within a
      hierarchical path modeling framework. In addition to finding age-related decrease
      in both perceptual priming and learning, the authors observed several
      dissociations with regards to their neural and cognitive mediators. Larger visual
      cortex volume was associated with greater repetition priming, but not perceptual
      skill learning, and neither process depended upon hippocampal volume. In
      contrast, the volumes of the prefrontal gray and white matter were differentially
      related to both processes via direct and indirect effects of cognitive resources.
      The results indicate that age-related differences in perceptual priming and skill
      learning have dissociable cognitive and neural correlates.

PMID- 19586216
TI  - Word memory test performance in amnesic patients with hippocampal damage.
AB  - Many symptom validity tests (SVTs) assess performance validity via declarative
      memory paradigms. One widely used SVT, the Word Memory Test (WMT), uses a variety
      of memory tests to assess performance. It is well known that declarative memory
      requires the hippocampus and related medial temporal lobe structures. In the
      present study, WMT performance was examined in nonlitigating amnesic subjects (n
      = 3) with well-documented focal bilateral hippocampal atrophy who were
      nondemented and otherwise cognitively unimpaired compared with matched controls.
      The amnesic subjects had no external incentives. Amnesic subjects performed
      significantly below the level of matched comparison subjects but above
      established cutoff scores on the immediate recognition and delay recognition
      subtests and consistency component. In contrast, the amnesic subjects were
      impaired relative to our comparison subjects on the multiple-choice, paired
      associate, free-recall, and long delay free-recall subtests and had extremely low
      performance on these measures. Thus, there was a differential effect of
      hippocampal damage on WMT performance where the recognition subtests were
      performed within the normal range, yet the free recall was profoundly impaired in
      amnesic subjects. Such an approach where SVT performance is assessed in
      populations with well-known cognitive impairments adds breadth to SVT clinical
      interpretations.

PMID- 19586217
TI  - Attention, automaticity, and developmental dyscalculia.
AB  - People suffering from developmental dyscalculia (DD) show an abnormal pattern of
      the size congruity effect. They do not display a facilitation component in a
      numerical Stroop task. In this task, participants are presented with 2 digits
      that differ both in physical size and numerical value, and they have to compare
      the digits while ignoring one of the dimensions. The present study examined
      performance of those with DD and control participants in the numerical Stroop
      task under cognitive load. The no-load condition replicated previous findings
      (i.e., lack of facilitation in the physical task for the DD group). Load had
      opposite effects on interference and facilitation. Load eliminated facilitation
      and increased interference in the control group. Load increased interference only
      in the physical task in the DD group. The opposite effect of load on facilitation
      and interference suggests that these components are related to different
      cognitive mechanisms. The fact that load produced a DD-like pattern in the
      control group could suggest that individuals with DD suffer from difficulty in
      recruiting attention in addition to the deficits in numerical processing.

PMID- 19586218
TI  - Impact of enhanced resources on anticipatory stress and adjustment to new
      information technology: a field-experimental test of conservation of resources
      theory.
AB  - An intervention based on conservation of resources theory was conducted in an
      organization installing new information technology (IT) to enhance participants'
      psychological resources and thereby reduce anticipated stress and facilitate
      adjustment to the new IT. Before installation, 218 IT users in 25 units
      participated in 5 days of technical training; only the randomly assigned
      experimental group also participated in a "resource workshop." All participants
      filled out questionnaires before the workshop, 2 weeks later, and 2 months after
      the IT installation. ANOVA detected a significant increase in users' means
      efficacy in the experimental group and a decline in the control group. The new IT
      caused the control users more dissatisfaction and exhaustion, whereas the
      experimental users were spared these increases in strain, as predicted.
      Implications for theory and practice are discussed.

PMID- 19586219
TI  - An examination of the relationship between workload and fatigue within and across
      consecutive days of work: is the relationship static or dynamic?
AB  - Cognitive-energetical theories of information processing were used to generate
      predictions regarding the relationship between perceived workload and fatigue
      within and across consecutive days of work. Repeated measures were taken aboard a
      naval vessel from a sample of 20 Navy patrol vessel crew members during
      nonroutine and routine patrols. The hypotheses were tested through growth curve
      modeling. There was a nonmonotonic relationship between workload and fatigue in
      the routine patrol; moderate workload was associated with the lowest fatigue. The
      relationship between workload and fatigue changed over consecutive days in the
      nonroutine patrol. At the beginning of the patrol, low workload was associated
      with fatigue. At the end of the patrol, high workload was associated with
      fatigue. These results suggest that the optimal level of workload can change over
      time and thus have implications for the management of fatigue, particularly where
      prolonged operations are involved.

PMID- 19586220
TI  - Feeling recovered and thinking about the good sides of one's work.
AB  - Consistent with a positive psychology perspective, this longitudinal study
      investigated relations between positive and negative nonwork experiences (i.e.,
      feeling recovered, thinking about the positive and negative aspects of one's work
      during leisure time) with different job performance dimensions. In total, 358
      employees working with persons with special needs responded to two questionnaires
      at an interval of 6 months. Results from hierarchical regression analyses showed
      that feeling recovered during leisure time predicted an increase in task
      performance after 6 months. This relation was mediated by occupational self
      efficacy. Positive work reflection was found to predict an increase in proactive
      behavior (personal initiative, creativity) and organizational citizenship
      behavior. Negative work reflection was unrelated to job performance. Our results
      emphasize the role of positive nonwork experiences for employees' job
      performance.

PMID- 19586221
TI  - Stress and counterproductive work behavior: multiple relationships between
      demands, control, and soldier indiscipline over time.
AB  - Cognitive Resource Theory (CRT) suggests that under high levels of stress,
      employees are more prone to committing indiscipline. As few studies have examined
      this relationship over time, the authors conducted a six-wave longitudinal study
      examining the relationship of soldiers' indiscipline with work demands and
      control. The study included archival data collected quarterly over 2 years from
      1,701 soldiers representing 10 units in garrison (Germany and Italy), in training
      rotations (Grafenwoehr, Germany), and on peacekeeping deployments (Kosovo,
      Kuwait). No main effects were found for work overload, and the findings for the
      moderating effects of control were contradictory. Within each time point, as work
      overload increased, soldiers who felt less control committed more indiscipline,
      supporting CRT. Over time, however, as work overload increased, soldiers who
      perceived less control 6 months earlier committed less indiscipline.
      Additionally, the authors found reverse causal effects for control such that
      prior perceptions of a lack of control were associated with indiscipline and
      prior incidents of indiscipline with less control.

PMID- 19586222
TI  - Patterns and profiles of response to incivility in the workplace.
AB  - The authors draw on stress and coping theory to understand patterns of individual
      response to workplace incivility. According to data from 3 employee samples,
      incivility tended to trigger mildly negative appraisals, which could
      theoretically differentiate incivility from other categories of antisocial work
      behavior. Employees experiencing frequent and varied incivility from powerful
      instigators generally appraised their uncivil encounters more negatively. They
      responded to this stressor using a multifaceted array of coping strategies, which
      entailed support seeking, detachment, minimization, prosocial conflict avoidance,
      and assertive conflict avoidance. These coping reactions depended on the target's
      appraisal of the situation, the situation's duration, and the organizational
      position and power of both target and instigator. Implications for organizational
      science and practice are discussed.

PMID- 19586223
TI  - How do stressors lead to burnout? The mediating role of motivation.
AB  - We extend existing stressor-strain theoretical models by including intrinsic
      motivation as a mediator between well-established job stressors and burnout.
      Though the link between situational stressors and burnout is well established,
      little is known about mechanisms behind this relationship. With a sample of 284
      self-employed individuals, we examined motivation as a mediator to explain why
      situational factors impact 3 dimensions of burnout: emotional exhaustion,
      cynicism, and inefficacy. Motivation is an explanatory mechanism that drives
      human behavior and thought, and thus may have an impact on important well-being
      outcomes. As expected, intrinsic motivation was a full mediator for the effect of
      perceived fit on the inefficacy dimension of burnout. Unexpectedly, neither
      perceived fit nor motivation was related to the other 2 dimensions of burnout,
      and role ambiguity had only a direct effect on the inefficacy dimension; it was
      also unrelated to exhaustion and cynicism. We discuss implications of these
      findings for researchers as well as for practitioners.

PMID- 19586224
TI  - Distributive justice, procedural justice, and psychological distress: the
      moderating effect of coworker support and work autonomy.
AB  - Recent research has demonstrated that the perception of injustice at work may
      increase psychological health-related problems. The purpose of this study is to
      examine the moderating effect of coworker support and work autonomy on the
      relationships between both distributive and procedural justice and psychological
      distress. Results, on the basis of responses to questionnaires given to 248
      prison employees, show that coworker support moderates the relationships between
      both forms of justice and psychological distress. Specifically, these
      relationships are weakened when employees benefit from a high level of coworker
      support. Furthermore, work autonomy moderates the relationship between procedural
      justice and psychological distress but not the relationship between distributive
      justice and psychological distress. Thus, procedural injustice is less likely to
      increase psychological distress when the level of work autonomy is high.

PMID- 19586225
TI  - Exploring relationships among anger, perceived organizational support, and
      workplace outcomes.
AB  - The present study examines anger within a perceived organizational support (POS)
      theory framework. Using structural equation modeling, the authors explored
      relationships among POS, anger, and workplace outcomes in a sample of 1,136
      employees in 21 stores of a U.S. retail organization. At both individual and
      store levels, low POS was directly associated with greater anger. At the
      individual level, anger partially mediated relationships among low POS and
      turnover intentions, absences, and accidents on the job. Anger had direct and
      indirect effects on alcohol consumption and health-related risk taking. At the
      store level, anger had direct negative effects on inventory loss and turnover.
      The authors interpret these findings in light of social exchange theory and
      emotion regulation theory.

PMID- 19586226
TI  - Do the opportunities for learning and personal development lead to happiness? It
      depends on work-family conciliation.
AB  - The study shows how the perceptions of opportunities for learning and personal
      development predict five dimensions of affective well-being (AWB: pleasure,
      comfort, placidity, enthusiasm, and vigor), and how this relationship is
      moderated by the perceptions of work-family conciliation. A sample comprising 404
      individuals was collected. The findings show the following: (1) both the
      perceptions of opportunities for learning and personal development and
      perceptions of work-family conciliation predict AWB, the happier individuals
      being those who have high perceptions on both variables; (2) both variables
      interact in predicting AWB, in such a way that perceptions of high opportunities
      for learning and personal development may not lead to higher AWB if work-family
      conciliation is low. Post hoc analysis also suggests that the relationship
      between the perceptions of opportunities for learning and personal development
      and AWB tends to be nonlinear for individuals with perceptions of low work-family
      conciliation.

PMID- 19586227
TI  - Effects of voucher-based intervention on abstinence and retention in an
      outpatient treatment for cocaine addiction: a randomized controlled trial.
AB  - The aims of this study were to assess whether voucher magnitude improved cocaine
      abstinence and retention in an outpatient treatment for cocaine dependence, and
      to determine the effectiveness of a contingency management intervention in a
      European cultural context. A randomized controlled trial was conducted in which
      96 participants who were randomly assigned to 1 of 3 treatment conditions in a
      community setting: standard outpatient treatment, community reinforcement
      approach (CRA) plus low monetary value vouchers (each point earned was equivalent
      to 0.125 Euro, US$ 0.18), and CRA plus high monetary value vouchers (each point
      was worth 0.25 Euro, US$ 0.36). In the standard treatment group, mean percentage
      of cocaine-negative samples was 88.45%, versus 96.09% in the CRA plus low
      vouchers group, and 97.07% in the CRA plus high-vouchers group. Retention rate at
      6 months was 36.5% in the standard treatment group, 53.3% in the CRA plus low
      vouchers group, and 69.0% in the CRA plus high-vouchers group. The CRA plus
      vouchers groups obtained better results than the standard program. This study
      showed that treating cocaine addiction by combining CRA with vouchers was more
      effective than standard treatment in community outpatient programs in Spain.

PMID- 19586228
TI  - The relationship between self-efficacy and reductions in smoking in a contingency
      management procedure.
AB  - Social--cognitive and behavioral theories of change disagree on what the relevant
      controlling variables for initiating behavior change are. Correlations between
      baseline smoking cessation self-efficacy and the changes in breath carbon
      monoxide (CO) and the reduction in breath CO and increases in smoking cessation
      self-efficacy from baseline were obtained from a contingency management smoking
      cessation procedure. A test of the difference between the cross-lag correlations
      suggested a nonspurious causal relationship between smoking cessation self
      efficacy and changes in breath CO. Path analyses showed that decreases in breath
      CO (reductions in smoking) predicted later increases in smoking cessation self
      efficacy. Baseline self-reports of smoking cessation self-efficacy were not
      significantly correlated with subsequent changes in breath CO. Rather,
      significant correlations were found between reductions in breath CO and later
      increases in smoking cessation self-efficacy. These results suggest that self
      efficacy may be a cognitive response to one's own behavior, and are inconsistent
      with a social--cognitive view of self-efficacy's role in behavior change.
      Implications for the development of smoking cessation programs and health
      promoting behavior changes in general are discussed.

PMID- 19586229
TI  - The acceptability, safety, and tolerability of methadone/naloxone in a 50:1
      ratio.
AB  - Methadone is an effective therapy for heroin addiction, but the public health
      benefits are compromised by diversion and injection of prescribed methadone.
      Combination with naloxone is one way to reduce the risk of diversion and
      injection. Two studies were conducted. The first ascertained the safety,
      tolerability, pharmacokinetics, and pharmacodynamics of oral methadone-naloxone
      in a 50:1 ratio compared with methadone. The second study investigated the
      effectiveness of intramuscularly injected methadone-naloxone in precipitating
      withdrawal in methadone-maintained subjects. The first double-blind, crossover
      study randomized 10 stable methadone-maintained subjects equally to receive
      either methadone-naloxone or methadone over two alternate 14 day periods. In the
      second study, 5 subjects received intramuscular injections of methadone-naloxone
      before their scheduled methadone dose. Oral methadone-naloxone in a 50:1 ratio
      appeared to be well tolerated, although a taste difference between the
      preparations may have compromised blinding. There were no significant differences
      between methadone and methadone-naloxone in objective and subjective opioid
      withdrawal signs, and trough and peak plasma concentrations. Methadone-naloxone
      in a 50:1 ratio intramuscularly precipitated mild to moderate signs of opioid
      withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience
      withdrawal at a lower dose refused higher dose challenges. Withdrawal symptoms
      peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60
      minutes. Methadone-naloxone in 50:1 ratio has the pharmacological properties to
      be a useful combination product for treatment of heroin addiction with reduced
      risk of injection.

PMID- 19586230
TI  - Men and women, alcohol and aggression.
AB  - The purpose of this study was to examine the acute effects of alcohol on
      aggressive behavior in men and women in a laboratory setting. Participants were
      526 (261 men and 265 women) healthy social drinkers between 21 and 35 years of
      age. They were randomly assigned to either an alcohol or a placebo group.
      Aggression was measured using a modified version of the Taylor Aggression
      Paradigm in which electric shocks are received from, and delivered to, a same
      gender fictitious opponent during a supposed competitive interpersonal task.
      Aggression was operationalized as the intensity and duration of shocks that
      participants administered to their "opponent." Overall, men were more aggressive
      than women. Alcohol increased aggression for both men and women but this effect
      was stronger for men. This is one of the first laboratory studies to demonstrate
      that alcohol increases aggression in women.

PMID- 19586231
TI  - Relations between in-treatment and follow-up abstinence among cocaine-dependent
      homeless persons in three clinical trials.
AB  - Clinical trials with cocaine-dependent outpatients have found a strong relation
      between in-treatment and follow-up abstinence, and the strength of this relation
      is constant across treatment conditions with variable efficacy in generating
      abstinence. The authors conducted secondary analyses of data from 3 clinical
      trials to determine whether this relation generalizes to cocaine-dependent
      homeless persons. The 3 trials (total N = 543) were conducted in a community
      health care facility for homeless people. The 7 treatment arms across the 3
      trials were combinations of day treatment, abstinence-contingent housing, and
      vocational training. Drug use was measured with urine toxicology testing.
      Consecutive weeks of abstinence during treatment were strongly related to
      abstinence at the 12-month follow-up, whether or not missing 12-month data were
      included in the analysis. The treatment arms differed in their efficacy in
      generating abstinence, but the relation between in-treatment and follow-up
      abstinence did not differ across treatment arms. These results replicate earlier
      reports of these relations and extend them to a population of homeless people.
      The lack of differences between treatment arms in the in-treatment-follow-up
      abstinence relation implies that that relation is independent of the treatment
      specific intervention components that generate group differences in abstinence.

PMID- 19586232
TI  - Serotonin transporter genotype and depressive symptoms moderate effects of
      nicotine on spatial working memory.
AB  - Smokers may use nicotine to self-medicate for situation-specific or person
      specific cognitive or affective deficits. Although evidence suggests that
      nicotine replacement therapy (NRT), relative to placebo, enhances spatial working
      memory (SWM) in smoking-abstinent smokers with schizophrenia, the extent to which
      NRT may be helpful in attenuating abstinence-related SWM in other groups with
      deficits in SWM is unknown. Depressive symptoms are associated with both tobacco
      smoking and deficits in SWM. Previous studies have found that smoking abstinence
      increases depressive affect and depression-related hemispheric asymmetries in
      brain activation. Although the serotonin neurotransmitter system is closely
      associated with depression and the effects of nicotine, the authors are not aware
      of any studies that have evaluated the possible role of individual differences in
      serotonin transporter (5-HTT) genotype and depressive symptoms as moderators of
      the effects of NRT on SWM. Thus, the current study assessed the effects of NRT
      (nicotine patch) on SWM in relation to: (1) depressive traits and (2) 5-HTT
      genotype. Smoking-deprived habitual smokers (N = 64) completed the dot recall
      test of SWM during counterbalanced and double-blind nicotine and placebo testing
      sessions. There was a marginal overall effect of NRT on SWM. More importantly,
      NRT enhanced SWM in 5-HTT short allele carriers, relative to those with two long
      alleles, and this enhancement in short-allele carriers was greater for
      individuals with higher levels of depressive symptoms.

PMID- 19586233
TI  - Anxiety sensitivity, acute nicotine withdrawal symptoms, and anxious and fearful
      responding to bodily sensations: a laboratory test.
AB  - The present investigation examined the moderating role of anxiety sensitivity
      (AS) in regard to the relation between acute nicotine withdrawal and anxious and
      fearful responding to a 10% carbon dioxide-enriched air (CO2) procedure. Ninety
      daily smokers (35 women; M(age) = 28.87, SD = 12.12) were assigned randomly to
      one of two groups (12-hr nicotine deprivation or smoking "as usual") and
      subsequently underwent a 10% CO2 provocation challenge. Partially consistent with
      prediction, results indicated that the AS by nicotine withdrawal (group status)
      interaction was significantly predictive of peri-challenge anxiety ratings
      (anxiety during the challenge), but not skin conductance reactivity. Findings are
      discussed in the context of the role of AS in amplifying smoking-based fear
      responses to bodily sensations.

PMID- 19586234
TI  - The combined effects of memantine and fluoxetine on an animal model of obsessive
      compulsive disorder.
AB  - Obsessive Compulsive Disorder (OCD) is currently treated with behavioral
      modification and psychotropic medications, with varying degrees of success. The
      most popular drugs for the treatment of OCD are the selective serotonin reuptake
      inhibitors (SSRIs). Another drug, the N-methyl-d-aspartate antagonist memantine,
      has recently been tested in the treatment of OCD. The present study investigates
      the effect of fluoxetine and memantine alone and in combination in a mouse model
      of compulsive behavior. In this model, compulsive scratching is induced by a
      subcutaneous injection of serotonin or a serotonin releasing agent, compound 48
      80, in the back of the neck. The effects of the memantine and fluoxetine
      combination were found to synergistic, specifically as defined by an isobologram.
      The results of the present investigation suggest the potential of a more
      effective management of the symptoms of OCD.

PMID- 19586235
TI  - Interaction of glia activation and neurotransmission in hippocampus of
      neuropathic rats treated with mirtazapine.
AB  - Recent studies have characterized a central nervous system neuroimmune effect in
      the analgesic mechanisms of antidepressants. Our study investigated the effect of
      a novel antidepressant mirtazapine on pro-inflammatory cytokines expression and
      astrocytic activation in hippocampus of neuropathic rats. L5 spinal nerve
      transection was made to produce mononeuropathic model. Mirtazapine was orally
      administered to rats that had been operated on daily for 14 days. Adrenergic or
      serotonergic receptor antagonist was intraperitoneally administered to examine
      their ability of blocking antinociceptive effect. In the region of hippocampus,
      TNFalpha and IL-1beta levels were assayed and the activity of astrocytes was
      immunostained with GFAP (glial fibrillary acidic protein) antibody. As a result,
      mirtazapine significantly inhibited the hyperalgesia produced by surgery, which
      was partially reversed by adrenergic and serotonergic antagonist. After surgery,
      the hippocampus demonstrated elevated TNFalpha and IL-1beta levels, concomitant
      with reactive astrocytes. Mirtazapine markedly reduced hippocampal cytokines
      production or astrocytic activation, which was blocked by both adrenergic and
      serotonergic antagonists. Our results indicate a possible role of hippocampal pro
      inflammatory cytokines and glia in the pathogenesis of neuropathic pain. A
      potential analgesic mechanism of mirtazapine may be inhibiting the above
      neuroimmune action through affecting adrenergic and serotonergic system.

PMID- 19586236
TI  - Egocentric pattern projection: how implicit personality theories recapitulate the
      geography of the self.
AB  - Five studies demonstrated egocentric pattern projection, in that the implicit
      personality theories (IPTs) that participants held about other people tended to
      recapitulate the terrain of their own personality. To the extent that
      participants believed they possessed 2 traits to a similar degree within
      themselves, they tended, through their judgments of others and estimates of
      population parameters, to claim that the 2 traits were positively correlated in
      other people; and if they believed they possessed 2 traits to a dissimilar degree
      within themselves, they tended to claim that the 2 traits were negatively
      correlated in other people. Further evidence showed that information about the
      self plays a causal role in the construction of implicit theories, making a
      unique contribution to the shape of IPTs over and above that of information about
      another person. The relevance of these data for recent controversies over
      egocentric social judgment is discussed.

PMID- 19586237
TI  - Understanding and using the Implicit Association Test: III. Meta-analysis of
      predictive validity.
AB  - This review of 122 research reports (184 independent samples, 14,900 subjects)
      found average r = .274 for prediction of behavioral, judgment, and physiological
      measures by Implicit Association Test (IAT) measures. Parallel explicit (i.e.,
      self-report) measures, available in 156 of these samples (13,068 subjects), also
      predicted effectively (average r = .361), but with much greater variability of
      effect size. Predictive validity of self-report was impaired for socially
      sensitive topics, for which impression management may distort self-report
      responses. For 32 samples with criterion measures involving Black-White
      interracial behavior, predictive validity of IAT measures significantly exceeded
      that of self-report measures. Both IAT and self-report measures displayed
      incremental validity, with each measure predicting criterion variance beyond that
      predicted by the other. The more highly IAT and self-report measures were
      intercorrelated, the greater was the predictive validity of each.

PMID- 19586238
TI  - Source entitativity and the elaboration of persuasive messages: the roles of
      perceived efficacy and message discrepancy.
AB  - Compared with nonentitative groups, entitative targets are considered to elicit
      more elaborative processing because of the singularity or unity they represent.
      However, when groups serve as sources of persuasive messages, other dynamics may
      operate. The current research suggests that entitativity is intrinsically linked
      to perceptions of a group's efficacy related to the advocacy, and this efficacy
      combines with the position of the appeal to determine message elaboration. When
      messages are counterattitudinal, entitative (efficacious) sources should elicit
      greater processing than nonentitative groups because of concern that the
      entitative sources may be more likely to bring about the negative outcomes
      proposed. However, when appeals are proattitudinal, sources low in entitativity
      (nonefficacious) should initiate more elaboration due to concern that they may be
      unlikely to facilitate the positive outcomes proposed. These hypotheses were
      supported in a series of studies. Preliminary studies established the
      entitativity-efficacy relation (Studies 1A and 1B). Primary persuasion studies
      showed that manipulations of source entitativity (Studies 2 and 3) and source
      efficacy (Studies 4A and 4B) have opposite effects on processing as a function of
      message discrepancy.

PMID- 19586240
TI  - Striving to be known by significant others: automatic activation of self
      verification goals in relationship contexts.
AB  - Extending research on the automatic activation of goals associated with
      significant others, the authors hypothesized that self-verification goals
      typically pursued with significant others are automatically elicited when a
      significant-other representation is activated. Supporting this hypothesis, the
      activation of a significant-other representation through priming (Experiments 1
      and 3) or through a transference encounter (Experiment 2) led participants to
      seek feedback that verifies their preexisting self-views. Specifically,
      significant-other primed participants desired self-verifying feedback, in general
      (Experiment 1), from an upcoming interaction partner (Experiment 2), and relative
      to acquaintance-primed participants and favorable feedback (Experiment 3).
      Finally, self-verification goals were activated, especially for relational self
      views deemed high in importance to participants' self-concepts (Experiment 2) and
      held with high certainty (Experiment 3). Implications for research on self
      evaluative goals, the relational self, and the automatic goal activation
      literature are discussed, as are consequences for close relationships.

PMID- 19586241
TI  - Intrasexual vigilance: the implicit cognition of romantic rivalry.
AB  - Four experiments tested the hypothesis that concerns about infidelity would lead
      people, particularly those displaying high chronic levels of romantic jealousy,
      to display a functionally coordinated set of implicit cognitive biases aimed at
      vigilantly processing attractive romantic rivals. Priming concerns about
      infidelity led people with high levels of chronic jealousy (but not those low in
      chronic jealousy) to attend vigilantly to physically attractive same-sex targets
      at an early stage of visual processing (Study 1), to strongly encode and remember
      attractive same-sex targets (Study 2), and to form implicit negative evaluations
      of attractive same-sex targets (Studies 3 and 4). In each case, effects were
      observed only for same-sex targets who were physically attractive-individuals who
      can pose especially potent threats to a person's own romantic interests. These
      studies reveal a cascade of implicit, lower order cognitive processes underlying
      romantic rivalry and identify the individuals most likely to display those
      processes. At a broader conceptual level, this research illustrates the utility
      of integrating social cognitive and evolutionary approaches to psychological
      science.

PMID- 19586242
TI  - The "me" I claim to be: cultural self-construal elicits self-presentational goal
      pursuit.
AB  - In 12 studies, respondents with an independent (vs. interdependent) self
      construal showed an increased tendency and readiness to present themselves as
      skillful and capable and a decreased tendency and readiness to present themselves
      as socially sensitive and appropriate. This emerged in the form of differential
      scores on direct measures of self-presentation-self-deceptive enhancement and
      impression management (Study 1), differential social sensitivity in a gift-giving
      scenario (Study 2), differential performance on questions assessing general
      knowledge (Studies 5-6) and etiquette (Studies 7-8), and different choices
      between tests purportedly measuring one's self-reliance versus social
      appropriateness (Studies 9A and 9D). These relationships were observed when
      participants focused on their own self-presentational concerns but disappeared
      when participants focused on others' outcomes (Study 3) or when they had a prior
      opportunity to satisfy their goals via self-affirmation (Studies 4, 5, 6, 7, 8,
      9B, 9D). Finally, self-construal effects were eliminated or reversed when
      participants were led to doubt their ability to achieve their self-presentational
      goals (Study 9C).

PMID- 19586243
TI  - Microbes, mating, and morality: individual differences in three functional
      domains of disgust.
AB  - What is the function of disgust? Whereas traditional models have suggested that
      disgust serves to protect the self or neutralize reminders of our animal nature,
      an evolutionary perspective suggests that disgust functions to solve 3
      qualitatively different adaptive problems related to pathogen avoidance, mate
      choice, and social interaction. The authors investigated this 3-domain model of
      disgust across 4 studies and examined how sensitivity to these functional domains
      relates to individual differences in other psychological constructs. Consistent
      with their predictions, factor analyses demonstrated that disgust sensitivity
      partitions into domains related to pathogens, sexuality, and morality. Further,
      sensitivity to the 3 domains showed predictable differentiation based on sex,
      perceived vulnerability to disease, psychopathic tendencies, and Big 5
      personality traits. In exploring these 3 domains of disgust, the authors
      introduce a new measure of disgust sensitivity. Appreciation of the functional
      heterogeneity of disgust has important implications for research on individual
      differences in disgust sensitivity, emotion, clinical impairments, and
      neuroscience.

PMID- 19586244
TI  - Testing a social-cognitive model of moral behavior: the interactive influence of
      situations and moral identity centrality.
AB  - This article proposes and tests a social-cognitive framework for examining the
      joint influence of situational factors and the centrality of moral identity on
      moral intentions and behaviors. The authors hypothesized that if a situational
      factor increases the current accessibility of moral identity within the working
      self-concept, then it strengthens the motivation to act morally. In contrast, if
      a situational factor decreases the current accessibility of moral identity, then
      it weakens the motivation to act morally. The authors also expected the influence
      of situational factors to vary depending on the extent to which moral identity
      was central to a person's overall self-conception. Hypotheses derived from the
      framework were tested in 4 studies. The studies used recalling and reading a list
      of the Ten Commandments (Study 1), writing a story using morally laden terms
      (Study 4), and the presence of performance-based financial incentives (Studies 2
      and 3) as situational factors. Participants' willingness to initiate a cause
      related marketing program (Study 1), lie to a job candidate during a salary
      negotiation (Studies 2 and 3), and contribute to a public good (Study 4) were
      examined. Results provide strong support for the proposed framework.

PMID- 19586245
TI  - Patterns and sources of adult personality development: growth curve analyses of
      the NEO PI-R scales in a longitudinal twin study.
AB  - The present study examined the patterns and sources of 10-year stability and
      change of adult personality assessed by the 5 domains and 30 facets of the
      Revised NEO Personality Inventory. Phenotypic and biometric analyses were
      performed on data from 126 identical and 61 fraternal twins from the Bielefeld
      Longitudinal Study of Adult Twins (BiLSAT). Consistent with previous research,
      LGM analyses revealed significant mean-level changes in domains and facets
      suggesting maturation of personality. There were also substantial individual
      differences in the change trajectories of both domain and facet scales.
      Correlations between age and trait changes were modest and there were no
      significant associations between change and gender. Biometric extensions of
      growth curve models showed that 10-year stability and change of personality were
      influenced by both genetic as well as environmental factors. Regarding the
      etiology of change, the analyses uncovered a more complex picture than originally
      stated, as findings suggest noticeable differences between traits with respect to
      the magnitude of genetic and environmental effects.

PMID- 19586246
TI  - Clarifying the role of social comparison in the big-fish-little-pond effect
      (BFLPE): an integrative study.
AB  - It has been speculated that the big-fish-little-pond effect (BFLPE; the negative
      impact of highly selective academic settings on academic self-concept) is a
      consequence of invidious social comparisons experienced in higher ability
      schools. However, the direct role of such comparisons for the BFLPE has not
      heretofore been documented. The present study comprises the first evidence that
      the BFLPE (a) is eliminated after controlling for students' invidious comparisons
      with their class and (b) coexists with the assimilative and contrastive effects
      of upward social comparison choices on academic self-concept. These results
      increase understanding of the BFLPE and offer support for integrative approaches
      of social comparison (selective accessibility and interpretation comparison
      models) in a natural setting. They also lend support for the distinction between
      forced and deliberate social comparisons and the usefulness of distinguishing
      between absolute and relative comparison-level choice in self-assessment.

PMID- 19586247
TI  - Cross-national variation in the size of sex differences in values: effects of
      gender equality.
AB  - How does gender equality relate to men's and women's value priorities? It is
      hypothesized that, for both sexes, the importance of benevolence, universalism,
      stimulation, hedonism, and self-direction values increases with greater gender
      equality, whereas the importance of power, achievement, security, and tradition
      values decreases. Of particular relevance to the present study, increased gender
      equality should also permit both sexes to pursue more freely the values they
      inherently care about more. Drawing on evolutionary and role theories, the
      authors postulate that women inherently value benevolence and universalism more
      than men do, whereas men inherently value power, achievement, and stimulation
      more than women do. Thus, as gender equality increases, sex differences in these
      values should increase, whereas sex differences in other values should not be
      affected by increases in gender equality. Studies of 25 representative national
      samples and of students from 68 countries confirmed the hypotheses except for
      tradition values. Implications for cross-cultural research on sex differences in
      values and traits are discussed.

PMID- 19586249
TI  - A model of motor inhibition for a complex skill: baseball batting.
AB  - The ability to inhibit an ongoing action in response to a signal from the
      environment is important for many perceptual-motor actions. This paper examines a
      particular example of this behavior: attempting to inhibit or "check" a swing in
      baseball batting. A model of motor inhibition in batting is proposed. In the
      model there are three different inhibition signals (out of range launch angle,
      early expected-actual trajectory discrepancy, and late expected-actual trajectory
      discrepancy) resulting in four possible response outcomes for the batter's swing
      (full swing, inhibited swing, partial response, or interrupted swing). The
      predictions of the model were compared with the actual batting performance of 20
      baseball players using a high-fidelity batting simulator. The proportions of the
      different response outcomes could be explained by the inhibition model for 17/20
      of the batters in the study. These findings suggest that models of motor
      inhibition developed for simple, discrete tasks can be applied to complex,
      multistage behaviors. This batting inhibition model could be used to provide a
      quantitative measure of a player's bat control for training and player-screening
      purposes. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19586248
TI  - What is being assessed and why it matters: the impact of transient error on trait
      research.
AB  - Temporal instability can reflect either true psychological change or transient
      measurement error, and it is important that trait psychologists be able to
      distinguish one from the other. The authors report results from large retest
      studies of Big Five, trait affectivity, and personality disorder measures across
      time frames (2 months and 2 weeks) over which these constructs should show little
      or no true change. On average, nearly 25% of the variance in the measures was a
      product of transient error rather than true change; however, the proportion of
      error varied widely-but consistently-across measures. In addition, a
      reexamination of long-term longitudinal data demonstrated that ignoring transient
      error can lead to inaccurate conclusions. Most notably, a substantial portion of
      the observed instability in the Big Five and trait affectivity is due to
      transient error; thus, these traits are even more stable than commonly thought.
      The present data further suggest that previous reports of differential stability
      between the Big Five and trait affectivity are due, in part, to differential
      levels of transient error in measures of these constructs.

PMID- 19586250
TI  - A theory and model of conflict detection in air traffic control: incorporating
      environmental constraints.
AB  - A performance theory for conflict detection in air traffic control is presented
      that specifies how controllers adapt decisions to compensate for environmental
      constraints. This theory is then used as a framework for a model that can fit
      controller intervention decisions. The performance theory proposes that
      controllers apply safety margins to ensure separation between aircraft. These
      safety margins are formed through experience and reflect the biasing of decisions
      to favor safety over accuracy, as well as expectations regarding uncertainty in
      aircraft trajectory. In 2 experiments, controllers indicated whether they would
      intervene to ensure separation between pairs of aircraft. The model closely
      predicted the probability of controller intervention across the geometry of
      problems and as a function of controller experience. When controller safety
      margins were manipulated via task instructions, the parameters of the model
      changed in the predicted direction. The strength of the model over existing and
      alternative models is that it better captures the uncertainty and decision biases
      involved in the process of conflict detection. (PsycINFO Database Record (c) 2009
      APA, all rights reserved).

PMID- 19586251
TI  - The cost of search for multiple targets: effects of practice and target
      similarity.
AB  - With the use of X-ray images, performance in the simultaneous search for two
      target categories was compared with performance in two independent searches, one
      for each category. In all cases, displays contained one target at most. Dual
      target search, for both categories simultaneously, produced a cost in accuracy,
      although the magnitude of this dual-target cost was affected by the nature of the
      targets. When target feature sets shared values, accuracy in dual-target search
      was equivalent to that in the less accurate of the two single-target searches.
      However, when targets comprised different feature sets, accuracy in dual-target
      search was lower than in either single-target search. These results held after
      practice. In conclusion, dual-target search performance depends on the target
      representations required for search. When combined representations contain
      conflicting values within the most informative feature dimensions, then there is
      a cost in performance. When target representations share features, the search can
      be guided by the common values so that resources are not wasted on irrelevant
      distractors. The implication is that security screener performance might be
      improved by specializing in searching for threat categories that share features.
      (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19586253
TI  - Robustness of the sequential lineup advantage.
AB  - A growing movement in the United States and around the world involves promoting
      the advantages of conducting an eyewitness lineup in a sequential manner. We
      conducted a large study (N = 2,529) that included 24 comparisons of sequential
      versus simultaneous lineups. A liberal statistical criterion revealed only 2
      significant sequential lineup advantages and 3 significant simultaneous
      advantages. Both sequential advantages occurred when the good photograph of the
      guilty suspect or either innocent suspect was in the fifth position in the
      sequential lineup; all 3 simultaneous advantages occurred when the poorer quality
      photograph of the guilty suspect or either innocent suspect was in the second
      position. Adjusting the statistical criterion to control for the multiple tests
      (.05/24) revealed no significant sequential advantages. Moreover, despite finding
      more conservative overall choosing for the sequential lineup, no support was
      found for the proposal that a sequential advantage was due to that conservative
      criterion shift. Unless lineups with particular characteristics predominate in
      the real world, there appears to be no strong preference for conducting lineups
      in either a sequential or a simultaneous manner. (PsycINFO Database Record (c)
      2009 APA, all rights reserved).

PMID- 19586254
TI  - Univariate and default standard unit biases in estimation of body weight and
      caloric content.
AB  - College students estimated the weight of adult women from either photographs or a
      live presentation by a set of models and estimated the calories in 1 of 2 actual
      meals. The 2 meals had the same items, but 1 had larger portion sizes than the
      other. The results suggest: (a) Judgments are biased toward transforming the
      example in question to the size and/or properties of a "standard" unit. For
      estimates of body weight, students assigned weights assuming a standard height,
      even though height information was provided in the photographs or directly
      present with live models. (b) There is an inclination to focus on 1 aspect or
      dimension of the stimulus (e.g., for female figures, their width, for meals the
      identity of the components as opposed to their size) and either devalue or
      completely ignore another parameter critical for accurate judgment (height, for
      the case of body weight estimations). That is, students defaulted to a normative
      unit size and thus treated the stimulus as a representative, categorical, and
      unvarying example, and focused on only 1 dimension (univariate bias) in making
      judgments. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19586255
TI  - Test length and cognitive fatigue: an empirical examination of effects on
      performance and test-taker reactions.
AB  - Person and situational determinants of cognitive ability test performance and
      subjective reactions were examined in the context of tests with different time-on
      task requirements. Two hundred thirty-nine first-year university students
      participated in a within-participant experiment, with completely counterbalanced
      treatment conditions and test forms. Participants completed three test sessions
      of different length: (a) a standard-length SAT test battery (total time 4(1/2)
      hr), (b) a shorter SAT test battery (total time 3(1/2) hr), and (c) a longer SAT
      test battery (total time 5(1/2) hr). Consistent with expectations, subjective
      fatigue increased with increasing time-on-task. However, mean performance
      increased in the longer test length conditions, compared with the shorter test
      length condition. Individual differences in personality/interest/motivation trait
      complexes were found to have greater power than the test-length situations for
      predicting subjective cognitive fatigue before, during, and at the end of each
      test session. The relative contributions of traits and time-on-task for cognitive
      fatigue are discussed, along with implications for research and practice.
      (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 19586256
TI  - Visual priming of inverted and rotated objects.
AB  - Object images are identified more efficiently after prior exposure. Here, the
      authors investigated shape representations supporting object priming. The
      dependent measure in all experiments was the minimum exposure duration required
      to correctly identify an object image in a rapid serial visual presentation
      stream. Priming was defined as the change in minimum exposure duration for
      identification as a function of prior exposure to an object. Experiment 1
      demonstrated that this dependent measure yielded an estimate of predominantly
      visual priming (i.e., free of name and concept priming). Experiments 2 and 3
      demonstrated that although identification [corrected] was sensitive to
      orientation, visual priming was relatively invariant with image inversion (i.e.,
      an image visually primed its inverted counterpart approximately as much as it
      primed itself). Experiment 4 demonstrated a similar dissociation with images
      rotated 90 degrees off the upright. In all experiments, the difference in the
      magnitude of priming for identical or rotated-inverted priming conditions was
      marginal or nonexistent. These results suggest that visual representations that
      support priming can be relatively insensitive to picture-plane manipulations,
      although these manipulations have a substantial effect on object identification.

PMID- 19586257
TI  - Can imageability help us draw the line between storage and composition?
AB  - Language requires both storage and composition. However, exactly what is
      retrieved from memory and what is assembled remains controversial, especially for
      inflected words. Here, "imageability effects" is introduced as a new diagnostic
      of storage and a complement to frequency effects. In 2 studies of past-tense
      morphology, more reliable imageability and frequency effects were found on
      irregulars than on regulars. An interaction with sex was also observed: Males but
      not females showed more reliable frequency and imageability effects for
      irregulars than for regulars; females but not males showed signs of storage for
      regulars, particularly among higher frequency forms. Overall, the findings
      validate imageability effects as another diagnostic of storage and suggest that
      the line between storage and computation is not a simple function; rather, it
      depends upon the interplay of both item- and subject-specific factors.

PMID- 19586258
TI  - Models of quantitative estimations: rule-based and exemplar-based processes
      compared.
AB  - The cognitive processes underlying quantitative estimations vary. Past research
      has identified task-contingent changes between rule-based and exemplar-based
      processes (P. Juslin, L. Karlsson, & H. Olsson, 2008). B. von Helversen and J.
      Rieskamp (2008), however, proposed a simple rule-based model-the mapping model
      that outperformed the exemplar model in a task thought to promote exemplar-based
      processing. This raised questions about the assumptions of rule-based versus
      exemplar-based models that underlie the notion of task contingency of cognitive
      processes. Rule-based models, such as the mapping model, assume the abstraction
      of explicit task knowledge. In contrast, exemplar models should profit if storage
      and activation of the exemplars is facilitated. Two studies tested the importance
      of the two models' assumptions. When knowledge about cues existed, the rule-based
      mapping model predicted quantitative estimations best. In contrast, when
      knowledge about the cues was difficult to gain, participants' estimations were
      best described by an exemplar model. The results emphasize the task contingency
      of cognitive processes.

PMID- 19586259
TI  - Integrated and independent learning of hand-related constituent sequences.
AB  - In almost all daily activities fingers of both hands are used in coordinated
      succession. The present experiments explored whether learning in such tasks
      pertains not only to the overall sequence spanning both hands but also to the
      constituent sequences of each hand. In a serial reaction time task, 2 repeating
      hand-related sequences were intertwined, so that actions of one hand alternated
      with actions of the other hand. Integrated learning of the overall sequence was
      weak when the constituent sequences were uncorrelated (Experiment 1) and massive
      when they were correlated (Experiment 2). Both experiments yielded evidence
      suggesting partly independent learning of the hand-related sequences. There were
      no reliable indications of intermanual transfer of this hand-related sequence
      knowledge. The findings suggest that after sufficient training of coordinated
      action sequences involving several limbs, a part of the acquired sequence
      knowledge begins to be represented in an effector-specific manner.

PMID- 19586260
TI  - Separable brain systems supporting cued versus self-initiated realization of
      delayed intentions.
AB  - In everyday life, one can link anticipated specific cues (e.g. visiting a
      restaurant) with desired actions (e.g., ordering a healthy meal). Alternatively,
      intentions such as "I intend to eat more healthily" present the option to act
      when one encounters the same cue. In the first case, a specific cue triggers a
      specific action; in the second, one must act in a more self-initiated manner. The
      authors compared such scenarios using functional magnetic resonance imaging.
      Participants were either instructed to respond in a particular manner to target
      events (cued condition) or told that they would score points for such responses,
      without being told that they were necessary (self-initiated condition). Although
      conditions differed only in the wording of instructions, the self-initiated
      condition was associated with poorer performance and greater activity in a
      predominantly frontoparietal network. Responses to targets in the self-initiated
      and cued conditions yielded greater activity in lateral and medial Brodmann area
      10, respectively. The authors suggest that these results reflect differing
      demands for self-initiated versus externally cued behavior following different
      types of instruction, in line with the distinction between goal intentions and
      implementation intentions proposed by P. M. Gollwitzer and colleagues.

PMID- 19586261
TI  - Surprise, memory, and retrospective judgment making: testing cognitive
      reconstruction theories of the hindsight bias effect.
AB  - Hindsight bias has been shown to be a pervasive and potentially harmful decision
      making bias. A review of 4 competing cognitive reconstruction theories of
      hindsight bias revealed conflicting predictions about the role and effect of
      expectation or surprise in retrospective judgment formation. Two experiments
      tested these predictions examining the effects of manipulating the information
      presented in a text-based scenario and its congruency with the given outcome on
      surprise, hindsight bias, and recall. The results of Experiment 1 revealed
      evidence of hindsight bias after exposure to incongruent and ambivalent outcomes
      but not after exposure to congruent outcomes. Experiment 2 replicated the
      hindsight bias results and found that the ratio of outcome consistent information
      recalled was higher than expected in the incongruent and ambivalent conditions
      but equaled the ratio presented to participants in the congruent condition. The
      results were interpreted as supporting the general predictions of sense-making
      models of the hindsight bias. A refined version of this model is discussed.

PMID- 19586262
TI  - Are independent probes truly independent?
AB  - The independent cue technique has been developed to test traditional interference
      theories against inhibition theories of forgetting. In the present study, the
      authors tested the critical criterion for the independence of independent cues:
      Studied cues not presented during test (and unrelated to test cues) should not
      contribute to the retrieval process. Participants first studied a subset of cues
      (e.g., rope) that were subsequently studied together with a target in a 2nd study
      phase (e.g., rope-sailing, sunflower-yellow). In the test phase, an extralist
      category cue (e.g., sports, color) was presented, and participants were
      instructed to recall an item from the study list that was a member of the
      category (e.g., sailing, yellow). The experiments showed that previous study of
      the paired-associate word (e.g., rope) enhanced category cued recall even though
      this word was not presented at test. This experimental demonstration of covert
      cuing has important implications for the effectiveness of the independent cue
      technique.

PMID- 19586263
TI  - The quiet clam is quite calm: transposed-letter neighborhood effects on eye
      movements during reading.
AB  - In responses time tasks, inhibitory neighborhood effects have been found for word
      pairs that differ in a transposition of two adjacent letters (e.g., clam/calm).
      Here, the author describes two eye-tracking experiments conducted to explore
      transposed-letter (TL) neighborhood effects within the context of normal silent
      reading. In Experiment 1, sentences contained a target word that either has a TL
      neighbor (e.g., angel, which has the TL neighbor angle) or does not (e.g.,
      alien). In Experiment 2, the context was manipulated to examine whether semantic
      constraints attenuate neighborhood effects. Readers took longer to process words
      that have a TL neighbor than control words but only when either member of the TL
      pair was likely. Furthermore, this interference effect occurred very late in
      processing and was not affected by relative word frequency. These interference
      effects can be explained either by the spreading of activation from the target
      word to its TL neighbor or by the misidentification of target words for their TL
      neighbors. Implications for models of orthographic input coding and models of eye
      movement control are discussed.

PMID- 19586264
TI  - A global theory of remembering and forgetting from multiple lists.
AB  - Forgetting is frustrating, usually because it is unintended. Other times, one may
      purposely attempt to forget an event. A global theory of recognition and free
      recall that explains both types of forgetting and remembering from multiple list
      experiments is presented. The critical assumption of the model is that both
      intentional and unintentional forgetting are often due to contextual
      interference. Unintentional forgetting is the natural result of contextual
      changes between study and test. Intentional forgetting is accomplished by a
      rapid, metacognitively instigated change in mental context that renders to-be
      forgotten information relatively inaccessible and renders to-be-remembered
      information more accessible (L. Sahakyan & C. M. Kelley, 2002). This occurs for
      both recognition and free recall. Implications for item-method directed
      forgetting, exclusion recognition, source memory, and encoding operations are
      discussed.

PMID- 19586265
TI  - Unsuccessful retrieval attempts enhance subsequent learning.
AB  - Taking tests enhances learning. But what happens when one cannot answer a test
      question-does an unsuccessful retrieval attempt impede future learning or enhance
      it? The authors examined this question using materials that ensured that
      retrieval attempts would be unsuccessful. In Experiments 1 and 2, participants
      were asked fictional general-knowledge questions (e.g., "What peace treaty ended
      the Calumet War?"). In Experiments 3-6, participants were shown a cue word (e.g.,
      whale) and were asked to guess a weak associate (e.g., mammal); the rare trials
      on which participants guessed the correct response were excluded from the
      analyses. In the test condition, participants attempted to answer the question
      before being shown the answer; in the read-only condition, the question and
      answer were presented together. Unsuccessful retrieval attempts enhanced learning
      with both types of materials. These results demonstrate that retrieval attempts
      enhance future learning; they also suggest that taking challenging tests-instead
      of avoiding errors-may be one key to effective learning.

PMID- 19586266
TI  - Operation-specific effects of numerical surface form on arithmetic strategy.
AB  - Educated adults solve simple addition problems primarily by direct memory
      retrieval, as opposed to by counting or other procedural strategies, but they
      report using retrieval substantially less often with problems in written-word
      format (four + eight) compared with digit format (4 + 8). It was hypothesized
      that retrieval efficiency is relatively low with word operands compared with
      digits and that this promotes a shift to procedural backup strategies. Consistent
      with this hypothesis, Experiment 1 demonstrated greater word-format costs on
      retrieval usage for addition than subtraction, which was due to increased
      counting for addition but not subtraction. Experiment 2 demonstrated greater word
      format costs on retrieval for division than multiplication, which was due to
      increased use of multiplication-fact reference to solve division problems. Format
      related strategy shifts away from retrieval reflected both the efficiency of
      retrieval for a given operation and the availability of viable alternative
      strategies. The results demonstrate that calculation processes are not abstracted
      away from problem surface form. The authors propose that retrieval efficiency for
      arithmetic connects diverse performance and strategy-related effects across key
      arithmetic factors, including arithmetic operation, numerical size, and numeral
      format.

PMID- 19586267
TI  - Visual and spatial working memory are not that dissociated after all: a time
      based resource-sharing account.
AB  - Examinations of interference between visual and spatial materials in working
      memory have suggested domain- and process-based fractionations of visuo-spatial
      working memory. The present study examined the role of central time-based
      resource sharing in visuo-spatial working memory and assessed its role in
      obtained interference patterns. Visual and spatial storage were combined with
      both visual and spatial on-line processing components in computer-paced working
      memory span tasks (Experiment 1) and in a selective interference paradigm
      (Experiment 2). The cognitive load of the processing components was manipulated
      to investigate its impact on concurrent maintenance for both within-domain and
      between-domain combinations of processing and storage components. In contrast to
      both domain- and process-based fractionations of visuo-spatial working memory,
      the results revealed that recall performance was determined by the cognitive load
      induced by the processing of items, rather than by the domain to which those
      items pertained. These findings are interpreted as evidence for a time-based
      resource-sharing mechanism in visuo-spatial working memory.

PMID- 19586268
TI  - Lexical competition during second-language listening: sentence context, but not
      proficiency, constrains interference from the native lexicon.
AB  - A spoken language eye-tracking methodology was used to evaluate the effects of
      sentence context and proficiency on parallel language activation during spoken
      language comprehension. Nonnative speakers with varying proficiency levels viewed
      visual displays while listening to French sentences (e.g., Marie va decrire la
      poule [Marie will describe the chicken]). Displays depicted several objects
      including the final noun target (chicken) and an interlingual near-homophone
      (e.g., pool) whose name in English is phonologically similar to the French target
      (poule). Listeners' eye movements reflected temporary consideration of the
      interlingual competitor when hearing the target noun, demonstrating cross
      language lexical competition. However, competitor fixations were dramatically
      reduced when prior sentence information was incompatible with the competitor
      (e.g., Marie va nourrir... [Marie will feed...]). In contrast, interlingual
      competition from English did not vary according to participants' rated
      proficiency in French, even though proficiency reliably predicted other aspects
      of processing behavior, suggesting higher proficiency in the active language does
      not provide a significant independent source of control over interlingual
      competition. The results provide new insights into the nature of parallel
      language activation in naturalistic sentential contexts.

PMID- 19586269
TI  - Better learning with more error: probabilistic feedback increases sensitivity to
      correlated cues in categorization.
AB  - Despite the fact that categories are often composed of correlated features, the
      evidence that people detect and use these correlations during intentional
      category learning has been overwhelmingly negative to date. Nonetheless, on other
      categorization tasks, such as feature prediction, people show evidence of
      correlational sensitivity. A conventional explanation holds that category
      learning tasks promote rule use, which discards the correlated-feature
      information, whereas other types of category learning tasks promote exemplar
      storage, which preserves correlated-feature information. Contrary to that common
      belief, the authors report 2 experiments that demonstrate that using
      probabilistic feedback in an intentional categorization task leads to sensitivity
      to correlations among nondiagnostic cues. Deterministic feedback eliminates
      correlational sensitivity by focusing attention on relevant cues. Computational
      modeling reveals that exemplar storage coupled with selective attention is
      necessary to explain this effect.

PMID- 19586270
TI  - Predicting category intuitiveness with the rational model, the simplicity model,
      and the generalized context model.
AB  - Naive observers typically perceive some groupings for a set of stimuli as more
      intuitive than others. The problem of predicting category intuitiveness has been
      historically considered the remit of models of unsupervised categorization. In
      contrast, this article develops a measure of category intuitiveness from one of
      the most widely supported models of supervised categorization, the generalized
      context model (GCM). Considering different category assignments for a set of
      instances, the authors asked how well the GCM can predict the classification of
      each instance on the basis of all the other instances. The category assignment
      that results in the smallest prediction error is interpreted as the most
      intuitive for the GCM-the authors refer to this way of applying the GCM as
      "unsupervised GCM." The authors systematically compared predictions of category
      intuitiveness from the unsupervised GCM and two models of unsupervised
      categorization: the simplicity model and the rational model. The unsupervised GCM
      compared favorably with the simplicity model and the rational model. This success
      of the unsupervised GCM illustrates that the distinction between supervised and
      unsupervised categorization may need to be reconsidered. However, no model
      emerged as clearly superior, indicating that there is more work to be done in
      understanding and modeling category intuitiveness.

PMID- 19586271
TI  - The sensory nature of episodic memory: sensory priming effects due to memory
      trace activation.
AB  - The aim of this study was to provide evidence that memory and perceptual
      processing are underpinned by the same mechanisms. Specifically, the authors
      conducted 3 experiments that emphasized the sensory aspect of memory traces. They
      examined their predictions with a short-term priming paradigm based on 2 distinct
      phases: a learning phase consisting of the association between a geometrical
      shape and a white noise and a priming phase examining the priming effect of the
      geometrical shape, seen in the learning phase, on the processing of target tones.
      In the 3 experiments, the authors found that only the prime associated with the
      sound in the learning phase had an effect on the target processing. The
      perceptual nature of the auditory component reactivated by the prime was shown in
      Experiments 1 and 2 via manipulation of the white noise duration in the learning
      phase and the stimulus onset asynchrony in the priming phase. Moreover,
      Experiment 3 highlighted the importance of the simultaneous association of
      sensory components in the learning phase, which makes it possible to integrate
      these components in a memory trace.

PMID- 19586272
TI  - Complex span versus updating tasks of working memory: the gap is not that deep.
AB  - How to best measure working memory capacity is an issue of ongoing debate.
      Besides established complex span tasks, which combine short-term memory demands
      with generally unrelated secondary tasks, there exists a set of paradigms
      characterized by continuous and simultaneous updating of several items in working
      memory, such as the n-back, memory updating, or alpha span tasks. With a latent
      variable analysis (N = 96) based on content-heterogeneous operationalizations of
      both task families, the authors found a latent correlation between a complex span
      factor and an updating factor that was not statistically different from unity (r
      = .96). Moreover, both factors predicted fluid intelligence (reasoning) equally
      well. The authors conclude that updating tasks measure working memory equally
      well as complex span tasks. Processes involved in building, maintaining, and
      updating arbitrary bindings may constitute the common working memory ability
      underlying performance on reasoning, complex span, and updating tasks.

PMID- 19586273
TI  - Women match men when learning a spatial skill.
AB  - Meta-analytic studies have concluded that although training improves spatial
      cognition in both sexes, the male advantage generally persists. However, because
      some studies run counter to this pattern, a closer examination of the anomaly is
      warranted. The authors investigated the acquisition of a basic skill (spatial
      selective attention) using a matched-pair two-wave longitudinal design.
      Participants were screened with the use of an attentional visual field task, with
      the objective of selecting and matching 10 male-female pairs, over a wide range
      (30% to 57% correct). Subsequently, 20 participants 17-23 years of age (selected
      from 43 screened) were trained for 10 hr (distributed over several sessions) by
      playing a first-person shooter video game. This genre is known to be highly
      effective in enhancing spatial skills. All 20 participants improved, with matched
      members of the male-female pairs achieving very similar gains, independent of
      starting level. This is consistent with the hypothesis that the learning
      trajectory of women is not inferior to that of men when acquiring a basic spatial
      skill. Training methods that develop basic spatial skills may be essential to
      achieve gender parity in both basic and complex spatial tasks.

PMID- 19586275
TI  - Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine
      pulmonary tuberculosis.
AB  - A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and
      pharmacokinetic characteristics of tuberculosis therapeutics. While membrane
      transporters play important roles in drug disposition and physiological
      homeostasis, their expressional changes and contribution have never been analysed
      in a tuberculosis animal model. The mRNA expression level of 20 Abc family
      transporters and 32 Slc family transporters in tuberculosis-infected mice were
      compared with those in naive uninfected mice using real-time polymerase chain
      reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic
      expression changes of families of both Abc transporters and Slc transporters at 4
      and 8 weeks, as observed in the livers, kidneys, and intestines of test mice--and
      in a different mode, in the lungs and spleens as well. These changes were
      dependent on the tuberculosis progression with the tissue-specific manner, that
      is, in the lungs, the number of transporters of which the expression level
      changed due to M. tuberculosis infection had increased, and the magnitude of
      change also greater at 8 weeks, while in the spleen, the transcription of most
      transporters except Mrps had not changed or had recovered back to the same level
      of naive transcription at 8 weeks. Understanding the expression changes of
      transporters will assist in setting up rational preclinical dosing plans through
      the ability to predict the pharmacokinetics of new anti-tuberculosis
      chemotherapeutics and, furthermore, will assist in the design of safer and more
      efficient drug regimens.

PMID- 19586284
TI  - An optical dynamic mass redistribution assay reveals biased signaling of
      dualsteric GPCR activators.
AB  - Increasing attention is paid in basic science and in drug discovery to pathway
      selective intracellular signaling as a novel approach to achieve precise control
      of cell function via G protein-coupled receptors (GPCRs). With respect to
      signaling, GPCRs are often promiscuous in that more than one intracellular
      biochemical pathway is activated upon receptor stimulation by the endogenous
      transmitter or by exogenous drugs. We studied signaling by a novel class of GPCR
      activators that were designed to bind simultaneously to the orthosteric
      transmitter-binding site and the allosteric site of muscarinic acetylcholine
      receptors. An optical biosensor technique was applied to measure activation
      induced dynamic mass redistribution (DMR) in CHO cells stably expressing the
      muscarinic receptor subtype of interest. The use of tools to modulate signaling
      and measuring G protein activation directly proved that DMR is a valid and
      comfortable approach to gain real-time insight into intracellular signaling
      pathway activation and to identify signaling pathway-selective drugs.

PMID- 19586312
TI  - Guest editorial: special issue for Prof. Dr. Peter Paul Speiser.

PMID- 19586313
TI  - Evaluation of early osteochondral defect repair in a rabbit model utilizing
      fourier transform-infrared imaging spectroscopy, magnetic resonance imaging, and
      quantitative T2 mapping.
AB  - CONTEXT: Evaluation of the morphology and matrix composition of repair cartilage
      is a critical step toward understanding the natural history of cartilage repair
      and efficacy of potential therapeutics. In the current study, short-term
      articular cartilage repair (3 and 6 weeks) was evaluated in a rabbit
      osteochondral defect model treated with thrombin peptide (TP-508) using magnetic
      resonance imaging (MRI), quantitative T2 mapping, and Fourier transform-infrared
      imaging spectroscopy (FT-IRIS). METHODS: Three-mm-diameter osteochondral defects
      were made in the rabbit trochlear groove and filled with either TP-508 plus poly
      lactoglycolidic acid microspheres or poly-lactoglycolidic acid microspheres alone
      (placebo). Repair tissue and adjacent normal cartilage were evaluated at 3 and 6
      weeks postdefect creation. Intact knees were evaluated by magnetic resonance
      imaging for repair morphology, and with quantitative T2 mapping to assess
      collagen orientation. Histological sections were evaluated by FT-IRIS for
      parameters that reflect collagen quantity and quality, as well as proteoglycan
      (PG) content. RESULTS AND CONCLUSION: There was no significant difference in
      volume of repair tissue at either time point. At 6 weeks, placebo repair tissue
      demonstrated longer T2 values (p < 0.01) than TP-508 did. Although both placebo
      and TP-508 repair tissue demonstrated longer T2 values than adjacent normal
      cartilage did, the 6-week T2 values of the TP-508 specimens were closer to those
      of the adjacent normal cartilage than were the placebo values. FT-IRIS analysis
      demonstrated a significant increase in collagen content, integrity, and PG
      content of the TP-508 repair tissue from 3 to 6 weeks (p < or = 0.05). In
      addition, the collagen and PG content of the TP-508 samples were closer to normal
      cartilage at 3 weeks than were the placebo samples. Further, there was a
      significant inverse correlation between the T2 relaxation values and collagen
      orientation in the normal cartilage. However, there were no significant
      correlations between T2 relaxation values and any FT-IRIS parameter in the repair
      tissue. Together, the data demonstrate that MRI and FT-IRIS assessment of
      cartilage repair tissue provide molecular information that furthers understanding
      of the cartilage repair process.

PMID- 19586317
TI  - Modulation of proliferation and differentiation of human anterior cruciate
      ligament-derived stem cells by different growth factors.
AB  - We have previously isolated and identified stem cells from human cruciate
      ligaments. The goal of this study was to evaluate the proliferation and
      differentiation abilities of ligament-derived stem cells (LSCs) cultured with
      growth factors, including fibroblast growth factor 2 (FGF-2), epidermal growth
      factor, and transforming growth factor-beta 1 (TGF-b1). The ligament tissues were
      obtained from patients with anterior cruciate ligament injuries receiving
      arthroscopic surgeries. LSCs were obtained by collagenase digestion and plating
      as previously reported. Surface immunophenotype and the potential for trilineage
      differentiation into osteoblasts, chondrocytes, and adipocytes were confirmed. It
      was found that proliferation of the cells was enhanced with the addition of FGF-2
      and TGF-b1. Upon TGF-b1 treatment, expression of collagen type I and type III,
      tenascin-c, fibronectin, and a-smooth muscle actin were significantly
      upregulated. Additionally, LSCs treated with TGF-b1 and FGF-2 increased the
      production of collagenous and noncollagenous extracellular matrix protein.
      Together, these results demonstrate that LSCs respond differently to various
      cytokines, and the results further validate the potential of using cruciate
      ligament tissue as a stem cell source for tissue engineering purposes.

PMID- 19586318
TI  - Human adipose-derived stem cells contribute to chondrogenesis in coculture with
      human articular chondrocytes.
AB  - Adipose tissue is easily available and contains high numbers of stem cells that
      are capable for chondrogenic differentiation. We hypothesize that a partial
      substitution of chondrocytes with autologous adipose-derived stem cells (ASC)
      might be a possible strategy to reduce the number of chondrocytes needed in
      matrix-associated autologous chondrocyte transplantation. To lay the ground, in
      vitro coculture experiments were performed using human chondrocytes and human
      ASC. Chondrocytes were obtained from donors undergoing matrix-associated
      autologous chondrocyte transplantation. ASC were isolated from liposuction
      material. Chondrocytes and ASC were seeded either in fibrin (Tisseel; Baxter,
      Vienna, Austria) or collagen matrix (Tissue Fleece; Baxter, Unterschleissheim,
      Germany). RNA for quantitative reverse transcriptase (RT)-polymerase chain
      reaction was isolated after 2 weeks of culture in chondrogenic medium, and after
      4 weeks samples were processed for histology. Related to the number of
      chondrocytes used, coculture with ASC led to strong increase in collagen type IX
      mRNA expression, which is an indicator for long-term stability of cartilage.
      Moderate upregulation was shown for SOX9, aggrecan, melanoma inhibitory activity,
      cartilage link protein 1, and cartilage oligomeric matrix protein mRNA. However,
      expression of collagen I and collagen II indicates the synthesis of fibrous
      tissue, which might be due to the use of dedifferentiated chondrocytes. Tisseel
      provided slightly better chondrogenic conditions than Tissue Fleece. These data
      support the possibility to take advantage of ASC in cartilage regeneration in
      conjunction with autologous chondrocytes.

PMID- 19586325
TI  - Cost implications of IV versus oral anti-angiogenesis therapies in patients with
      advanced renal cell carcinoma: retrospective claims database analysis.
AB  - OBJECTIVE: Angiogenesis inhibitors (AI) are promising novel treatments for
      patients with renal cell carcinoma (RCC). However, IV therapy may impose
      infection risk from IV catheters, and will include increased costs due to
      administration and transportation costs. This study evaluated the incremental
      costs associated with IV administration of selected AI therapies (bevacizumab off
      label) compared to oral therapies (sunitinib or sorafenib) for the treatment of
      RCC. METHODS: Patients with > or =2 RCC claims (ICD-9: 189.0, 198.0) were
      identified from a US commercial health insurance claims database from 1/2004 to
      12/2007. Patients receiving bevacizumab (n = 109) were matched 1:1 to patients
      receiving sorafenib or sunitinib, and observed from their first AI therapy claim
      until the last treatment date. AI, inpatient, outpatient and pharmacy costs were
      calculated on a per-patient per-month (PPPM) basis over the treatment period.
      Costs were compared between the IV AI group and each separate oral AI group using
      multivariate Tobit regressions for each category separately, adjusting for
      demographic and baseline clinical characteristics. This study assessed costs of
      treatment and did not evaluate the cost-effectiveness of AIs. RESULTS: Mean total
      medical costs were $13,351, $6998, and $8213 PPPM for bevacizumab, sorafenib, and
      sunitinib, respectively (p <0.05 for equality). Adjusted incremental total cost
      for the bevacizumab group was $4951 PPPM compared to sorafenib and $4610 PPPM
      compared to sunitinib (both p < 0.05). Bevacizumab patients incurred incremental
      PPPM outpatient services cost compared to sorafenib and sunitinib of $2772 and
      $2548, respectively (both p < 0.05). CONCLUSIONS: Assuming median progression
      free survival of 8.5 months as shown for bevacizumab (Bukowski, et al., J Clin
      Oncol 2007), the incremental costs would be estimated at $39 188-42 080 per
      patient compared to those treated with sunitinib or sorafenib. Assuming similar
      efficacies, oral AI therapies may result in cost savings to patients and
      healthcare payers over IV therapies.

PMID- 19586351
TI  - Chronic toxicology of cannabis.
AB  - INTRODUCTION: Cannabis is the most widely used illicit drug worldwide. As
      societies reconsider the legal status of cannabis, policy makers and clinicians
      require sound knowledge of the acute and chronic effects of cannabis. This review
      focuses on the latter. METHODS: A systematic review of Medline, PubMed,
      PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana,"
      "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198
      papers. This list was screened by hand, and papers describing mechanisms and
      those published in more recent years were chosen preferentially for inclusion in
      this review. FINDINGS: There is evidence of psychiatric, respiratory,
      cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis
      has now been implicated in the etiology of many major long-term psychiatric
      conditions including depression, anxiety, psychosis, bipolar disorder, and an
      amotivational state. Respiratory conditions linked with cannabis include reduced
      lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a
      dose-dependent manner with elevated rates of myocardial infarction and cardiac
      arrythmias. It is known to affect bone metabolism and also has teratogenic
      effects on the developing brain following perinatal exposure. Cannabis has been
      linked to cancers at eight sites, including children after in utero maternal
      exposure, and multiple molecular pathways to oncogenesis exist. CONCLUSION:
      Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular,
      and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all
      of which depend upon dose and duration of use.

PMID- 19586352
TI  - Diethylene glycol poisoning.
AB  - INTRODUCTION: Diethylene glycol (DEG) is a clear, colorless, practically
      odorless, viscous, hygroscopic liquid with a sweetish taste. In addition to its
      use in a wide range of industrial products, it has also been involved in a number
      of prominent mass poisonings spanning back to 1937. Despite DEG's toxicity and
      associated epidemics of fatal poisonings, a comprehensive review has not been
      published. METHODS: A summary of the literature on DEG was compiled by
      systematically searching OVID MEDLINE and ISI Web of Science. Further information
      was obtained from book chapters, relevant news reports, and web material. AIM:
      The aim of this review is to summarize all main aspects of DEG poisoning
      including epidemiology, toxicokinetics, mechanisms of toxicity, clinical
      features, toxicity of DEG, diagnosis, and management. EPIDEMIOLOGY: Most of the
      documented cases of DEG poisoning have been epidemics (numbering over a dozen)
      where DEG was substituted in pharmaceutical preparations. More often, these
      epidemics have occurred in developing and impoverished nations where there is
      limited access to intensive medical care and quality control procedures are
      substandard. TOXICOKINETICS: Following ingestion, DEG is rapidly absorbed and
      distributed within the body, predominantly to regions that are well perfused.
      Metabolism occurs principally in the liver and both the parent and the
      metabolite, 2-hydroxyethoxyacetic acid (HEAA), are renally eliminated rapidly.
      MECHANISMS OF TOXICITY: Although the mechanism of toxicity is not clearly
      elucidated, research suggests that the DEG metabolite, HEAA, is the major
      contributor to renal and neurological toxicities. CLINICAL FEATURES: The clinical
      effects of DEG poisoning can be divided into three stages: The first phase
      consists of gastrointestinal symptoms with evidence of inebriation and developing
      metabolic acidosis. If poisoning is pronounced, patients can progress to a second
      phase with more severe metabolic acidosis and evidence of emerging renal injury,
      which, in the absence of appropriate supportive care, can lead to death. If
      patients are stabilized, they may then enter the final phase with various delayed
      neuropathies and other neurological effects, sometimes fatal. TOXICITY OF DEG:
      Doses of DEG necessary to cause human morbidity and mortality are not well
      established. They are based predominantly on reports following some epidemics of
      mass poisonings, which may underestimate toxicity. The mean estimated fatal dose
      in an adult has been defined as approximately 1 mL/kg of pure DEG. MANAGEMENT:
      Initial treatment consists of appropriate airway management and attention to acid
      base abnormalities. Prompt use of fomepizole or ethanol is important in
      preventing the formation of the toxic metabolite HEAA; hemodialysis can also be
      critical, and assisted ventilation may be required. CONCLUSIONS: DEG ingestion
      can lead to serious complications that may prove fatal. Prognosis may be
      improved, however, with prompt supportive care and timely use of fomepizole or
      ethanol.

PMID- 19586353
TI  - In vitro oxime-assisted reactivation of paraoxon-inhibited human
      acetylcholinesterase and butyrylcholinesterase.
AB  - INTRODUCTION: Organophosphorus pesticides and nerve agents are highly toxic to
      humans and other living organisms, primarily because of their interaction with
      enzyme acetylcholinesterase. The aim of our study was to find suitable
      reactivators of acetylcholinesterase and butyrylcholinesterase and to recommend
      the most efficacious compounds for the next evaluation as antidotes for
      intoxication by pesticides. METHODS: Eighteen structurally different oxime
      reactivators were tested for their in vitro ability to reactivate paraoxon
      inhibited human erythrocyte acetylcholinesterase and human plasma
      butyrylcholinesterase to find out structure-activity relationship within this set
      of compounds. Their reactivation ability was compared with commercially available
      acetylcholinesterase reactivators (pralidoxime, methoxime, trimedoxime,
      obidoxime, and HI-6). RESULTS AND DISCUSSION: The best reactivation ability was
      achieved with obidoxime, trimedoxime, compounds K027, K075, K203, and K048. We
      have also tested reactivation of butyrylcholinesterase with the aim to recommend
      an efficient reactivator, able to perform a "pseudo catalytic" bioscavenger with
      butyrylcholinesterase, which is developed as new antidote of organophosphate
      poisonings. Such combination could allow an enhancement of prophylactic and
      therapeutic efficiency of administered enzyme. Compounds K117, K269, K075, and
      trimedoxime were found to be the most potent reactivators of inhibited
      butyrylcholinesterase. CONCLUSIONS: In this work, we have evaluated only
      reactivation of paraoxon-inhibited cholinesterases. To get better understanding
      of this problem, a larger number of organophosphorus inhibitors should be used.

PMID- 19586354
TI  - Alcohol intoxication requiring hospital admission in children and adolescents:
      retrospective analysis at the University Children's Hospital in the Slovak
      Republic.
AB  - BACKGROUND: Few epidemiological studies have investigated the problem of children
      and adolescents taken to hospital with acute alcohol intoxication. METHODS: We
      reviewed the medical records of children and adolescents aged <or= 18 years
      hospitalized with alcohol intoxication alone in the University Children's
      Hospital in Bratislava, Slovak Republic, during the years 1996-2005 and compared
      their characteristics between the first and the second 5-year time periods.
      RESULTS: 537 patients (273 boys and 264 girls) were admitted to the hospital with
      intentional acute alcohol intoxication (1.5% of all admissions and 34.2% of all
      intoxications) between 1996 and 2005. The average age of the patients with
      alcohol intoxication presenting to hospital was 15.1 +/- 1.7 and the youngest
      were 9-year-old children. The proportion of children admitted with alcohol
      intoxication increased every year (R(2) = 0.935) (p < 0.001). The average blood
      alcohol concentration was 1.98 +/- 0.57 g/L, and it increased in 2001-2005 in
      relation to the previous 5 years (p < 0.001). The highest estimated alcohol
      concentration (4.39 g/L) was found in the blood of a 17-year-old boy. The mean
      poisoning severity score was 1.53 +/- 0.61 and had increased in line with blood
      alcohol concentration for the years 2001-2005 (p < 0.001). CONCLUSIONS: The
      results of this analysis emphasize the severity of underage alcohol consumption
      by young people in the Slovak Republic. Measures are needed to decrease alcohol
      abuse in children and adolescents.

PMID- 19586355
TI  - Bioanalytical and clinical evaluation of 103 suspected cases of intoxications
      with psychoactive plant materials.
AB  - INTRODUCTION: Problems associated with the increasing abuse of plant-derived
      psychoactive substances have recently attracted attention. This study involved
      bioanalytical and clinical examinations of intoxication cases suspected to be
      linked to such plant materials. METHODS: Urine samples were collected at
      emergency wards in Sweden from patients who either admitted or were suspected of
      ingestion of psychoactive plant materials. The bioanalytical investigation
      employed a liquid chromatography-tandem mass spectrometry multicomponent method
      covering 10 plant-derived substances (atropine, dimethyltryptamine, ephedrine,
      harmaline, harmine, ibogaine, lysergic acid amide, psilocin, scopolamine, and
      yohimbine) and a gas chromatography-mass spectrometry method for asarone. Routine
      testing for illicit drugs was also performed. RESULTS: Over a 4-year period, 103
      urine samples collected from mainly young people (age range 13-52 years, median
      19) were studied. Among 53 cases where ingestion of any of the 11 plant-derived
      substances covered in this study was admitted or suspected, 41 (77%) could be
      confirmed bioanalytically. Nine of the 11 substances tested for were detected,
      the exceptions being ibogaine and yohimbine. Psilocin, originating from ingestion
      of hallucinogenic mushrooms, was the most frequent drug accounting for 54% of the
      cases. The most common means of drug acquisition (56%) was purchase over the
      Internet. CONCLUSION: The patients using psychoactive plant materials were mainly
      young and commonly used the Internet for drug acquisition. Having access to
      bioanalytical methods for detection of plant-derived psychoactives is therefore
      considered important, when providing clinical toxicology service.

PMID- 19586356
TI  - Risk assessment of isolated aripiprazole exposures and toxicities: a
      retrospective study.
AB  - STUDY OBJECTIVE: To characterize the clinical effects of acute isolated
      aripiprazole poisonings and to assess the toxic dose of this drug. METHODS: All
      isolated acute aripiprazole exposures reported to a poison control system from
      January 2002 through September 2006 were retrospectively reviewed. Patients with
      incomplete information or those lost to follow-up were excluded. RESULTS: A total
      of 286 cases were identified. Mean age was 18.9 years (SD 15.7), with a range of
      6 months-70 years. Seventy-seven patients (27%) were <or=6 years, 80 patients
      (28%) were 7-17 years, and 129 patients (45%) were >or=18 years. Doses were known
      in 255 patients (89%). Symptoms occurred in 158 patients (55%): somnolence 89
      (56%), tachycardia 32 (20%, heart rate 102-186), nausea/vomiting 29 (18%),
      dystonic reactions 21 (13%), tremor 9 (6%), agitation 3 (2%), dizziness 3 (2%),
      paresthesia 2 (1%), headache 2 (1%), dysphagia 1 (<1%), syncope 1 (<1%), minor
      facial swelling 1 (<1%), and hypotension 1 (<1%). None of the patients required
      intubation, and there were no deaths or EKG abnormalities. Median dose for
      symptomatic and asymptomatic groups were 25 and 15 mg, respectively, for <or=6
      years (p = 0.02); 60 and 30 mg for 7-17 years (p = 0.01); and 100 and 75 mg for
      >or=18 (p = 0.25). In comparison of drug groups (Group 1, <or=20 mg; Group 2, 21
      90 mg; Group 3, >or=91 mg), symptoms were more likely to occur in Group 2 versus
      Group 1 (OR 2.29, 95% CI 0.79-6.61) in patients <or=6 years; in Group 3 versus
      Group 1 (OR 3.39, 95% CI 1.07-10.73) followed by Group 2 versus Group 1 (OR 1.14,
      95% CI 0.36-3.56) in patients 7-17 years; and in Group 3 versus Group 1 (OR 1.36,
      95% CI 0.54-3.42) but not any more likely in Group 2 versus Group 1 (OR 0.92, 95%
      CI 0.33-2.52) in patients >or=18 years. CONCLUSIONS: Acute aripiprazole
      poisonings most commonly result in sedation, sinus tachycardia, nausea/vomiting,
      or dystonic reactions. Symptoms are more likely with doses above 90 mg, although
      pediatric patients can be affected at a lower dose.

PMID- 19586357
TI  - Assessing the need for communication training for specialists in poison
      information.
AB  - INTRODUCTION: Effective communication has been shown to be essential to physician
      patient communication and may be even more critical for poison control center
      (PCC) calls because of the absence of visual cues, the need for quick and
      accurate information exchange, and possible suboptimal conditions such as call
      surges. Professionals who answer poison control calls typically receive extensive
      training in toxicology but very little formal training in communication. METHODS:
      An instrument was developed to assess the perceived need for communication
      training for specialists in poison information (SPIs) with input from focus
      groups and a panel of experts. Requests to respond to an online questionnaire
      were made to PCCs throughout the United States and Canada. RESULTS: The 537
      respondents were 70% SPIs or poison information providers (PIPs), primarily
      educated in nursing or pharmacy, working across the United States and Canada, and
      employed by their current centers an average of 10 years. SPIs rated
      communication skills as extremely important to securing positive outcomes for PCC
      calls even though they reported that their own training was not strongly focused
      on communication and existing training in communication was perceived as only
      moderately useful. Ratings of the usefulness of 21 specific training units were
      consistently high, especially for new SPIs but also for experienced SPIs.
      Directors rated the usefulness of training for experienced SPIs higher for 5 of
      the 21 challenges compared to the ratings of SPIs. DISCUSSION: Findings support
      the need for communication training for SPIs and provide an empirical basis for
      setting priorities in developing training units.

PMID- 19586358
TI  - Life-threatening Torsades de Pointes resulting from "natural" cancer treatment.
AB  - INTRODUCTION: Nonradioactive cesium chloride (CsCl) is used by some alternative
      medicine advocates as a treatment for cancer. The therapy was proven to be
      neither safe nor effective. Chronic use of CsCl has resulted in cases with severe
      cardiotoxicity. CASE REPORT: A 65-year-old lady presented to our hospital's
      accident and emergency department with recurrent syncope attacks.
      Electrocardiogram monitoring showed QT prolongation and transient Torsades de
      Pointes (TDP) ventricular tachycardia. She was taking anticancer naturopathic
      drugs for 6 weeks before admission. One of her naturopathic drugs was
      subsequently confirmed containing 89% CsCl by weight. Besides conventional
      treatment of QT prolongation and TDP, the patient was given a 4-week course of
      oral Prussian blue to enhance gastrointestinal elimination of cesium. The serum
      half-life of cesium was reduced from 61.7 to 29.4 days after the use of Prussian
      blue. QT prolongation was normalized in 27 days. DISCUSSION: To our knowledge,
      this is the first published case of nonradioactive cesium poisoning treated with
      Prussian blue. A transient rise in serum cesium level was observed during
      Prussian blue therapy. Possible explanations for this observation include poor
      drug compliance during outpatient treatment and redistribution of cesium from
      body stores. CONCLUSION: Nonradioactive CsCl poisoning can result in severe
      cardiotoxicity with QT prolongation and TDP ventricular tachycardia. The key
      points in the management of nonradioactive cesium poisoning include cessation of
      cesium exposure, vigorous electrolytes replacement, and oral Prussian blue
      therapy.

PMID- 19586359
TI  - Bilateral pneumothorax following acute inhalation injury.
AB  - INTRODUCTION: Inhalation injury can be thermal and/or chemical. We report
      bilateral pneumothorax following acute inhalation injury. CASE REPORT: A male
      worker in an upholstery factory was confined in the tanning machine for 15 min.
      The device was used to contain sodium sulfate, sulfur dioxide, and sulfuric acid.
      On admission, he was confused with Glasgow coma scale score as 9. His vital signs
      were as follows: blood pressure, 80/58 mmHg; pulse rate, 114 bpm; respiratory
      rate, 30 bpm; temperature, 37.1 degrees C; and oxygen saturation, 48%. He was
      intubated. Physical examination disclosed extensive subcutaneous emphysema on the
      neck and pinkish foamy discharge from the mouth. Chest X-ray showed bilateral
      pneumothoraces and pneumomediastinum that warranted bilateral tube thoracostomy.
      Bronchoscopy demonstrated web-shaped hyperemic areas on the upper airway mucosa
      with aphtous lesions in the base. Extensive hemorrhage and edema were evident
      around epiglottis. The patient was admitted to the intensive care unit and
      mechanically ventilated. He was discharged without any sequelae on day 8.
      CONCLUSION: Exposure to irritant gases such as sulfuric acid and sulfur dioxide
      can cause severe pulmonary injury leading to pneumothorax and pneumomediastinum.

PMID- 19586360
TI  - Serotonin syndrome following sibutramine poisoning in a child, with sequential
      quantification of sibutramine and its primary and secondary amine metabolites in
      plasma.
AB  - OBJECTIVE: To report a case of serotonin syndrome (SS) after sibutramine overdose
      in a child. CASE REPORT: A 4-year-old girl was admitted 25 h after accidentally
      ingesting approximately 27 pills of sibutramine (15 mg, approximately 23 mg/kg).
      The child developed clinical features suggestive of SS, including diaphoresis,
      tachycardia, hypertension, agitation, insomnia, incoordination, hypertonia (lower
      limbs >> upper limbs), and hallucinations. Serum creatine phosphokinase levels
      reached a peak on day 3 (2,577 U/L, reference value <145), suggesting mild
      rhabdomyolysis. No relevant changes were detected in other laboratory
      examinations or in the electrocardiogram throughout the period of
      hospitalization. The quantification of sibutramine and the active metabolites, M1
      (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine), by liquid
      chromatography/electrospray ionization tandem mass spectrometry in six sequential
      samples collected from 25 to 147 h post-ingestion revealed a nonlinear decrease
      in the log-scale plasma concentrations. Treatment was only supportive and
      involved prolonged sedation to control the agitation, sleeplessness, and
      hypertension; no cyproheptadine was used. The patient was discharged on day 6 and
      follow-up revealed no sequelae. CONCLUSION: To our knowledge, this is the first
      report of SS after sibutramine overdose in a child, with sequential monitoring of
      the plasma levels of the drug and its two active metabolites. The growing
      consumption of weight reducing pills may increase the risk of unintentional acute
      toxic exposures in children.

PMID- 19586361
TI  - Plasma level of atropine after accidental ingestion of Atropa belladonna.
AB  - BACKGROUND: Ingestion of toxic plant constituents still poses a challenge in
      clinical management. The amount of berries ingested is often unclear and in the
      case of Atropa belladonna may affect clinical outcome. Plasma levels of atropine
      may thus be useful in confirming the cause of intoxication. CASE REPORT: A 48
      year-old man had ingested three handfuls of Atropa belladonna. Within 6 h he
      experienced phases of disorientation, aggressiveness, and tachycardia. He was
      initially treated with diazepam, an intravenous infusion of physostigmine and
      activated charcoal. After temporary improvement his clinical condition worsened
      and he was transferred to our toxicological intensive care unit. Here, ongoing
      sedation and continuous administration of physostigmine was necessary because of
      disorientation. In the early phase of hospitalization, a blood sample was taken
      and a muscarinic receptor total binding equivalent to binding of 130 microg/L
      atropine was determined by a radio receptor technique. Within 2 days the patient
      recovered completely and was discharged in a good general condition. CONCLUSION:
      Receptor binding may help confirm diagnosis and elucidate mechanisms in this type
      of exposure.

PMID- 19586362
TI  - Varenicline overdose in a teenager--a clinical pharmacology perspective.

PMID- 19586363
TI  - Subcutaneous crotaline Fab administration in a model of rattlesnake envenomation.

PMID- 19586367
TI  - Layer by layer three-dimensional tissue epitaxy by cell-laden hydrogel droplets.
AB  - The ability to bioengineer three-dimensional (3D) tissues is a potentially
      powerful approach to treat diverse diseases such as cancer, loss of tissue
      function, or organ failure. Traditional tissue engineering methods, however, face
      challenges in fabricating 3D tissue constructs that resemble the native tissue
      microvasculature and microarchitectures. We have developed a bioprinter that can
      be used to print 3D patches of smooth muscle cells (5 mm x 5 mm x 81 microm)
      encapsulated within collagen. Current inkjet printing systems suffer from loss of
      cell viability and clogging. To overcome these limitations, we developed a system
      that uses mechanical valves to print high viscosity hydrogel precursors
      containing cells. The bioprinting platform that we developed enables (i) printing
      of multilayered 3D cell-laden hydrogel structures (16.2 microm thick per layer)
      with controlled spatial resolution (proximal axis: 18.0 +/- 7.0 microm and distal
      axis: 0.5 +/- 4.9 microm), (ii) high-throughput droplet generation (1 s per
      layer, 160 droplets/s), (iii) cell seeding uniformity (26 +/- 2 cells/mm(2) at 1
      million cells/mL, 122 +/- 20 cells/mm(2) at 5 million cells/mL, and 216 +/- 38
      cells/mm(2) at 10 million cells/mL), and (iv) long-term viability in culture
      (>90%, 14 days). This platform to print 3D tissue constructs may be beneficial
      for regenerative medicine applications by enabling the fabrication of printed
      replacement tissues.

PMID- 19586368
TI  - Profiling muscle-specific microRNA expression after peripheral denervation and
      reinnervation in a rat model.
AB  - MicroRNAs (miRNAs) are a class of highly conserved, non-coding RNAs involved in
      post-transcriptional gene regulation. The muscle-specific miRNAs, miR-1, miR
      133a, and miR-206, are expressed in skeletal muscles and have been shown to
      contribute to muscle development. To profile their expression after sciatic nerve
      denervation and reinnervation, the soleus muscles of the rats were analyzed with
      quantitative real-time PCR at 1 week, 1 month, 2 months, and 4 months after the
      experiments. In addition, a combined approach using computational prediction by
      the miRanda website and the Agilent Whole Rat Genome 4 x 44 k oligo microarray
      experiment was performed to investigate the potential target genes of these three
      miRNAs in the denervated and reinnervated muscles. The results revealed that with
      the first downregulation of miR-1 and miR-133a within 1 month in the denervated
      muscle, the expression of miR-1 and miR-133 increased by approximately 2-fold at
      4 months after denervation and reinnervation; on the other hand, the expression
      of miR-206 was significantly increased to approximately 3-fold 1 month later only
      following reinnervation but not following denervation, and lasted at least for 4
      months. The expression pattern of miR-206 was different from that of miR-1 and
      miR-133a. Notably, two genes (Hnrpu and Npy) and one gene (Ptprd) were
      potentially regulated both in the denervated and reinnervated muscle by miR-1 and
      miR-133a, respectively. There were six potential target genes (Hnrpu, Lsamp,
      MGC108776, Mef2, Npy, and Ppfibp2) of the upregulated miR-206 in the reinnervated
      muscle. Among these, three (Hnrpu, Npy, and MGC108776) were potentially regulated
      by both miR-1 and miR-206. Because the Mef2 transcription factor was reported to
      promote the transformation of type II fast glycolytic fibers into type I slow
      oxidative fibers, the upregulation of miR-206 with decreased expression of the
      Mef2 transcript in the 4 month reinnervated muscle, which presented type II fiber
      predominance 4 months after nerve microanastomosis, might indicate the role of
      miR-206 in determining the fiber type after peripheral nerve regeneration.

PMID- 19586376
TI  - Implications of antiviral resistance of influenza viruses.

PMID- 19586377
TI  - Vaginal ulceration and local lymphadenopathy in an African immigrant.

PMID- 19586378
TI  - Is combination systemic therapy superior to monotherapy for enterococcal
      prosthetic joint infection?

PMID- 19586380
TI  - Tuberculosis transmission from patients with smear-negative pulmonary
      tuberculosis in sub-Saharan Africa.

PMID- 19586381
TI  - Placental malaria increases malaria risk in the first 30 months of life: not
      causal.

PMID- 19586383
TI  - HIV transmission by HIV-infected women using hormonal contraception.

PMID- 19586391
TI  - Life-supportive therapy withdrawal and length of stay in a large oncologic
      intensive care unit at the end of life.
AB  - We evaluated the factors associated with life-supportive therapy withdrawal
      (LSTW) and length-of-stay (LOS) of adult patients with cancer who died while in
      the intensive care unit (ICU). We performed chart review of adult patients with
      cancer who died in a 53-bed ICU of a comprehensive cancer center and evaluated
      the relative impact of demographic and clinical factors by using logistic
      regression and linear regression. A total of 267 patients were included in the
      study. Multivariate analysis showed that white patients were 2.52 times more
      likely to have LSTW than patients of other ethnicities (95% confidence interval
      1.23-5.15, p = 0.01). The mean LOS for patients with hematologic cancers was 7.7
      days, compared to only 4.8 days for those diagnosed with nonhematologic cancers
      (p = 0.01). Having a hematologic cancer, LSTW, or admission into the surgical
      oncologic ICU independently predicted increased LOS for those who died in the ICU
      (p < 0.001 p = 0.001, and p < 0.001, respectively). Cultural differences in
      dealing with the end-of-life process rooted in religious beliefs or language
      barriers and reflected in the utilization rates of LSTW by non-whites and whites
      may partially explain our findings. The difficult transition from curative to
      palliative care in the ICU is reflected by the increased LOS of patients who
      received LSTW, were diagnosed with hematologic cancers, or were admitted into the
      surgical unit.

PMID- 19586390
TI  - Comfort measures: a qualitative study of nursing home-based end-of-life care.
AB  - OBJECTIVE: To explore how staff recognize that a resident is dying and to present
      a typology of comfort measures. DESIGN: Exploratory, descriptive study involving
      qualitative methods and semistructured in-depth interviews with staff members of
      one nursing home. SETTING: A 120-bed nursing home that is part of a continuum of
      care from independent living, to residential care, rehabilitation, intermediate,
      dementia and skilled care. PARTICIPANTS: Forty-two staff members including
      administrators, nurses, certified nursing assistants (CNAs), social workers, and
      housekeepers. METHODS: On-site interviews were guided by a semistructured
      instrument that included open-ended questions such as, "How does care change when
      a resident is dying?" The interview also included questions about education,
      professional experience, and the frequency with which participants provide end-of
      life care. Interviews were audiotape recorded, transcribed, and analyzed using
      grounded theory techniques. Descriptive statistics were used to provide
      demographic data. RESULTS: Nursing home staff members identified physical,
      behavioral, and social indicators of an approaching death. Comfort care is the
      interrelationship between: (1) symptom management (e.g., pain, dyspnea, anorexia,
      and dry mouth), (2) family care (e.g. emotional support, death education), (3)
      interpersonal relationships (e.g., with residents, family) and, (4)
      complementarity between interdisciplinary roles. Comfort care is holistic and
      person-centered focusing on the interrelationship between physical, psychosocial,
      and spiritual issues. CONCLUSION: The terms comfort measures and comfort care are
      widely used in nursing homes but definitions and modes of delivery vary. In-depth
      exploration can be utilized to compare of current and existing practices and
      contribute knowledge about whether palliative care is provided in nursing homes
      and if so, how. Ultimately program comparisons can lead to improvements in
      nursing home-based end-of-life care and standards for the delivery of palliative
      care in this setting.

PMID- 19586392
TI  - Light in condensed matter in the upper atmosphere as the origin of homochirality:
      circularly polarized light from Rydberg matter.
AB  - Clouds of the condensed excited Rydberg matter (RM) exist in the atmospheres of
      comets and planetary bodies (most easily observed at Mercury and the Moon), where
      they surround the entire bodies. Vast such clouds are recently proposed to exist
      in the upper atmosphere of Earth (giving rise to the enormous features called
      noctilucent clouds, polar mesospheric clouds, and polar mesospheric summer radar
      echoes). It has been shown in experiments with RM that linearly polarized visible
      light scattered from an RM layer is transformed to circularly polarized light
      with a probability of approximately 50%. The circular Rydberg electrons in the
      magnetic field in the RM may be chiral scatterers. The magnetic and anisotropic
      RM medium acts as a circular polarizer probably by delaying one of the
      perpendicular components of the light wave. The delay process involved is called
      Rabi-flopping and gives delays of the order of femtoseconds. This strong effect
      thus gives intense circularly polarized visible and UV light within RM clouds.
      Amino acids and other chiral molecules will experience a strong interaction with
      this light field in the upper atmospheres of planets. The interaction will vary
      with the stereogenic conformation of the molecules and in all probability promote
      the survival of one enantiomer. Here, this strong effect is proposed to be the
      origin of homochirality. The formation of amino acids in the RM clouds is
      probably facilitated by the catalytic effect of RM.

PMID- 19586393
TI  - Experiments on mixotrophic protists and catastrophic darkness.
AB  - Catastrophically darkened photic zone conditions in water bodies are postulated
      to be induced by a diversity of mechanisms that are recorded in the geological
      record, including asteroid and comet impacts and large-scale volcanic eruptions.
      Giant wildfires, such as those that followed the great fires in Siberia in 1915,
      have been directly shown to cause large reductions in sunlight penetrating to the
      ground. Previous studies on the response of phototrophs to sudden prolonged
      darkness have focused on the survival of axenic strains. In this paper, we
      describe laboratory experiments to investigate the survival and growth of
      isolated and mixed cultures of freshwater and marine mixotrophs after 6 months of
      darkness and in the low light that would follow these events. Mixotrophs could
      survive 6 months of darkness. Some species used dissolved organic carbon, which
      can be released from dead biomass after loss of light and was shown to improve
      feeding rates. Mixotrophs also improved the survival and subsequent growth of
      obligate phototrophs at low light levels when grown in mixed cultures. The
      ability of mixotrophs to switch from photosynthesis to heterotrophy following
      sudden darkening would not only allow them to survive but to grow and contribute
      to active food chains. The experiments suggest that, following the return of
      light, resumption of photosynthesis can be rapid. These experiments improve our
      understanding of the collapse of photosynthesis following catastrophic darkening
      and emphasize the important role of mixotrophy in the resilience of the
      photosynthetic biosphere during such periods. We speculate on the implications
      for the Cretaceous-Tertiary impact event and periods of global freezing.

PMID- 19586394
TI  - The effect of evaporated salt solutions on the optical dating properties of JSC
      Mars-1: "seasoning" for a Mars soil simulant.
AB  - Optically stimulated luminescence dating, or optical dating, is an established
      terrestrial geochronometric technique that is being adapted to date sedimentary
      deposits and landforms on the surface of Mars. Recent discoveries have
      highlighted the astrobiological significance and occurrence of halite on the
      surface of Mars. The objective of the experiments in this study was to create a
      simplistic analogue of the sedimentary material that would result from
      evaporation of ion-containing pore water out of martian regolith and evaluate the
      influence the evaporated salts would have on in situ optical dating of silicate
      sediments. The radiation dose response, as measured by infrared stimulated
      luminescence (IRSL), from evaporated mixtures of JSC Mars-1 and solutions of
      sodium chloride and calcium sulfate was documented. The results suggest that the
      presence of CaSO(4) and NaCl within the aggregated particles does not have
      adverse effects on IRSL dose response and that aggregates of this type exhibit
      dose response characteristics that are appropriate for optical dating.

PMID- 19586395
TI  - Right buttock rash for thirty years in a patient from China.

PMID- 19586397
TI  - Zinc supplementation in elderly nursing home residents.

PMID- 19586398
TI  - Outdoor electric mosquito-killing apparatuses for malaria control in a
      hyperendemic area.

PMID- 19586399
TI  - On changes in cancer mortality among HIV-infected patients: is there an excess
      risk of death from pancreatic cancer?

PMID- 19586400
TI  - Favorable outcome of severe acute hepatitis B in a patient treated with
      antithrombin III and antiviral therapy.

PMID- 19586401
TI  - Is acquisition of methicillin-resistant Staphylococcus aureus an occupational
      hazard for medical students?

PMID- 19586402
TI  - Are statins applicable for the prevention and treatment of zygomycosis?

PMID- 19586409
TI  - Safety and tolerability of an antiasthma herbal Formula (ASHMI) in adult subjects
      with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation
      phase I study.
AB  - BACKGROUND: Complementary and alternative medicines are increasingly used for the
      treatment of asthma in Western countries. A novel three-herb antiasthma herbal
      medicine intervention (ASHMI; Sino-Lion Pharmaceutical Company; Shan Dong China)
      was demonstrated to be effective and safe in a murine model of asthma and in a
      preliminary clinical study in China. OBJECTIVE: The objective of this study was
      to evaluate the safety and tolerability of ASHMI in adult subjects with allergic
      asthma. DESIGN: Randomized, double-blind, placebo-controlled, dose escalation,
      phase I trial aimed at developing a botanical drug under the United States Food
      and Drug Administration Investigational New Drug title. INTERVENTIONS: Subjects
      received one of three doses of ASHMI or placebo: 600 mg (2 capsules); 1200 mg (4
      capsules); or 1800 mg (6 capsules) twice daily for 1 week. Four (4) ASHMI and 2
      placebo subjects were treated at each dose level. Subjects continued to use their
      conventional asthma medications for the duration of the study. OUTCOME MEASURES:
      Vital signs, physical examination, laboratory data, and electrocardiogram data
      were monitored throughout the study to assess occurrence of adverse events (AEs).
      Immunomodulatory studies were performed to evaluate the effect of ASHMI on
      cytokine, chemokine, and growth factor levels. RESULTS: Twenty (20) nonsmoking,
      allergic subjects with asthma were included in the study. Eight (8) subjects (4
      ASHMI and 4 placebo) reported mild gastrointestinal symptoms. No grade 3 AEs were
      observed during the study period. Vital signs, electrocardiogram findings, and
      laboratory results obtained at pre- and post-treatment visits remained within
      normal range. No abnormal immunologic alterations were detected. CONCLUSION: In
      this phase I study, ASHMI appeared to be safe and well tolerated by subjects with
      asthma. These findings allowed initiation of a larger phase II study to assess
      the efficacy of ASHMI.

PMID- 19586413
TI  - Relationship between initial vancomycin concentration-time profile and
      nephrotoxicity among hospitalized patients.
AB  - BACKGROUND: Data suggest that higher doses of vancomycin can increase the risk of
      nephrotoxicity. No study has been undertaken to determine the pharmacodynamic
      index (ie, the area under the curve [AUC] or the trough value) that best
      describes the relationship between vancomycin exposure and onset of
      nephrotoxicity. METHODS: A retrospective study was conducted among patients who
      received vancomycin for a suspected or proven gram-positive infection during the
      period from 1 January 2005 through 31 December 2006 at Albany Medical Center
      Hospital. Patients were included in our study if they (1) were > or =18 years
      old, (2) had an absolute neutrophil count of > or =1000 cells/mm(3), (3) received
      vancomycin for >48 h, (4) had 1 vancomycin trough level collected within 96 h of
      vancomycin therapy, and (5) had a baseline serum creatinine level of <2.0 mg/dL.
      Patients were excluded if they (1) had a diagnosis of cystic fibrosis, (2)
      received intravenous contrast dye within 7 days of starting vancomycin or during
      therapy, or (3) required vasopressor support during therapy. Demographics,
      comorbid conditions, and treatment data were collected. The highest observed
      vancomycin trough value within 96 h of initiation of vancomycin therapy and the
      estimated vancomycin AUC were analyzed as measures of vancomycin exposure. The
      vancomycin AUC value from 0 to 24 h at steady state (in units of mg x h/L) for
      each patient was estimated by use of the maximum a posteriori probability
      Bayesian procedure in ADAPT II. Nephrotoxicity was defined as an increase in
      serum creatinine level of 0.5 mg/dL or 50%, whichever was greater, following
      initiation of vancomycin therapy. Logistic and Cox proportional hazards
      regression models identified the vancomycin pharmacodynamic index that best
      describes the relationship between vancomycin exposure and toxicity. RESULTS:
      During the study period, 166 patients met the inclusion criteria. Both initial
      vancomycin trough values and 0-24-h at steady state AUC values were associated
      with nephrotoxicity in the bivariate analyses. However, the vancomycin trough
      value, modeled as a continuous variable, was the only vancomycin exposure
      variable associated with nephrotoxicity in the multivariate analyses.
      CONCLUSIONS: The results indicate that a vancomycin exposure-toxicity response
      relationship exists. The vancomycin trough value is the pharmacodynamic index
      that best describes this association.

PMID- 19586414
TI  - Disruption of tight junctions by cellulose sulfate facilitates HIV infection:
      model of microbicide safety.
AB  - BACKGROUND: The lack of biomarkers that are predictive of safety is a critical
      gap in the development of microbicides. The present experiments were designed to
      evaluate the predictive value of in vitro models of microbicide safety. METHODS:
      Changes in the epithelial barrier were evaluated by measuring transepithelial
      electrical resistance (TER) after exposure of human epithelial cells to candidate
      microbicides in a dual-chamber system. The significance of observed changes was
      addressed by challenging cultures with human immunodeficiency virus (HIV) and
      measuring the ability of virus to cross the epithelium and infect target T cells
      cultured in the lower chamber. RESULTS: Exposure to nonoxynol-9 (N-9) or
      cellulose sulfate (CS), but not 9-[2-(phosphonomethoxy)propyl]adenine (also
      referred to as tenofovir) or PRO2000, resulted in a rapid and sustained reduction
      in TER and a marked increase in HIV infection of T cells cultured in the lower
      chamber. Moreover, CS triggered nuclear factor kappaB activation in peripheral
      blood mononuclear cells and increased HIV replication in chronically infected U1
      cells. CONCLUSIONS: Epithelial barrier disruption and enhanced viral replication
      may have contributed to the increased risk of HIV acquisition observed in phase 3
      trials of N-9 and CS. Expansion of in vitro safety testing to include these
      models would provide a more stringent preclinical assessment of microbicide
      safety and may prove to be more predictive of clinical outcomes.

PMID- 19586415
TI  - Iron differentially regulates gene expression and extracellular secretion of
      Vibrio vulnificus cytolysin-hemolysin.
AB  - In a previous study, we showed that Vibrio vulnificus is a ferrophilic bacterium
      that requires high levels of available iron for growth. In the present study, we
      show that iron stimulates, in an unusual manner, the production of cytolysin
      hemolysin (VvhA), the most potent exotoxin produced by V. vulnificus. The vvhA
      gene possesses a putative ferric uptake regulator (Fur)-binding box in the
      regulatory region, andvvhA transcription was repressed by iron and de-repressed
      by fur mutation. However, extracellular secretion of VvhA was conversely
      increased by iron. Iron increased transcription of pilD, which encodes PilD, a
      component of the type II general secretion system responsible for extracellular
      VvhA secretion. These results indicate that iron increases extracellular VvhA
      secretion via the type II general secretion system, although it can repress vvhA
      transcription via Fur.

PMID- 19586417
TI  - BibA induces opsonizing antibodies conferring in vivo protection against group B
      Streptococcus.
AB  - We recently characterized the function of BibA, an immunogenic surface-associated
      antigen expressed by group B Streptococcus (GBS) that is involved in virulence.
      In this study, we performed a bibA gene variability analysis on a panel of 72
      clinical isolate strains. The bibA gene was present in all the strains analyzed,
      and 4 allelic variants, correlating with serotype, were identified. Moreover,
      although the BibA protein was expressed in all strains tested, only 54% of
      strains demonstrated surface exposure of the antigen in vitro. Importantly,
      expression of BibA on the bacterial surface was correlated with protection,
      because mice immunized with BibA were protected against challenge by a GBS strain
      with high levels of surface exposure of the antigen. In agreement with these
      findings, serum samples from mice immunized with recombinant BibA induced
      neutrophil-mediated in vitro opsonophagocytic killing of GBS. In conclusion, we
      propose BibA as a novel GBS vaccine candidate.

PMID- 19586416
TI  - Prospective cohort study of microbial and inflammatory events immediately
      preceding Escherichia coli recurrent urinary tract infection in women.
AB  - BACKGROUND: A prospective cohort study was conducted to characterize the temporal
      sequence of microbial and inflammatory events immediately preceding Escherichia
      coli recurrent urinary tract infection (rUTI). METHODS: Women with acute cystitis
      and a history of UTI within the previous year self-collected periurethral and
      urine samples daily and recorded measurements of urine leukocyte esterase,
      symptoms, and sexual intercourse daily for 3 months. rUTI strains were
      characterized by pulsed-field gel electrophoresis and genomic virulence
      profiling. Urinary cytokine levels were measured. RESULTS: There were 38 E. coli
      rUTIs in 29 of 104 women. The prevalence of periurethral rUTI strain carriage
      increased from 46% to 90% during the 14 days immediately preceding rUTI, with
      similar increases in same-strain bacteriuria (from 7% to 69%), leukocyte esterase
      (from 31% to 64%), and symptoms (from 3% to 43%), most notably 2-3 days before
      rUTI (P<.05 for all comparisons). Intercourse with periurethral carriage of the
      rUTI strain also increased before rUTI (P=.008). Recurrent UTIs preceded by
      bacteriuria, pyuria, and symptoms were caused by strains less likely to have P
      fimbriae than other rUTI strains (P=.002). CONCLUSIONS: Among women with frequent
      rUTIs, the prevalences of periurethral rUTI strain carriage, bacteriuria, pyuria,
      and intercourse dramatically increase over the days preceding rUTI. A better
      understanding of the pathogenesis of rUTI will lead to better prevention
      strategies.

PMID- 19586420
TI  - Sustained release oral fampridine in the treatment of multiple sclerosis.
AB  - BACKGROUND: Fampridine-SR is under submission as the first drug to be FDA
      approved with an indication specifically for multiple sclerosis symptoms.
      Compounded forms of the active agent of Fampridine-SR (4-aminopyridine) have been
      used in clinical practice for many years. Clinical trials have now been completed
      that demonstrate a robust capacity of the drug to meet stringent statistical and
      clinically meaningful end points. OBJECTIVE: To review the present understanding
      of multiple sclerosis, the proposed mechanism of action of Fampridine-SR in
      patients, the published data regarding its efficacy and safety in human clinical
      trials, and to discuss its potential clinical uses in MS. RESULTS/CONCLUSION:
      Fampridine-SR 10 mg twice a day has been shown to be safe and effective in
      improving the ambulation of patients with walking disability due to MS. It will
      probably find clinical application beyond this specific indication in a
      significant proportion of patients.

PMID- 19586421
TI  - Pharmacotherapy of endometrial cancer.
AB  - BACKGROUND: Endometrial cancer is the seventh most common malignancy among women
      worldwide. Despite most cases being diagnosed at an early stage, the death rate
      has increased steadily over the past 20 years. The lack of an effective,
      standardized adjuvant treatment for women at a high risk of recurrence has
      contributed to these disappointing results. OBJECTIVES: The goal of this review
      was to assess the role of hormonal and cytotoxic therapies in the adjuvant
      treatment of endometrial cancer. Once defined, an evidence-based management
      algorithm for this neoplasm was proposed. METHODS: A thorough literature search
      was undertaken using the Cochrane and Pubmed databases. Systematic reviews, meta
      analyses, and randomized controlled trials were first collected and critically
      analyzed. Other study types were secondarily considered when pertinent.
      CONCLUSIONS: The choice of the adjuvant therapy in early-stage endometrial cancer
      must be a patient-specific decision. Preliminary data suggest a role for
      chemotherapy in high-risk subgroups. However, further research is necessary to
      confirm this. To date, hormonal therapy has not been widely used in the
      management of early-stage disease, other than for conservative treatment in a
      fertility-sparing setting. Both hormonal and chemotherapy represent valuable
      therapeutic tools for the management of patients affected by advanced disease.

PMID- 19586418
TI  - Pneumococcal surface protein A contributes to secondary Streptococcus pneumoniae
      infection after influenza virus infection.
AB  - We compared the growth of Streptococcus pneumoniae mutants with a disruption in
      the gene for either pneumococcal surface protein A (PspA-), neuraminidase A (NanA
      ), or hyaluronidase (Hyl-) to that of the parental strain D39 by means of a
      competitive growth model in mice with and those without prior influenza virus
      infection. The numbers of total bacteria recovered from mice with prior influenza
      virus infection were significantly greater than those recovered from mice without
      prior influenza virus infection. Although the Hyl- and NanA- mutants did not
      display attenuation in mice with or without prior influenza virus infection, the
      PspA- mutant exhibited attenuation both in mice with and in mice without prior
      influenza virus infection. This defect was severe in influenza virus-infected
      mice, for which growth of the PspA- mutant was 1800-fold lower than that of the
      parental strain D39. Furthermore, PspA immunization significantly reduced
      secondary bacterial lung burdens and concentrations of specific markers of lung
      damage in mice receiving serotypes 2, 3, and 4 pneumococci. Our findings indicate
      that PspA contributes to secondary S. pneumoniae infection after influenza virus
      infection and that PspA immunization mitigates early secondary pneumococcal lung
      infections.

PMID- 19586419
TI  - Age-associated inflammation and toll-like receptor dysfunction prime the lungs
      for pneumococcal pneumonia.
AB  - BACKGROUND: Aging is associated with increased inflammation and risk of community
      acquired pneumonia. Streptococcus pneumoniae co-opts the nuclear factor kappa B
      (NFkB)-regulated proteins polymeric immunoglobulin receptor (pIgR) and platelet
      activating factor receptor (PAFr) to attach and invade cells. We sought to
      determine whether aging and chronic inflammation were associated with increased
      pIgR and PAFr levels in the lungs and increased susceptibility to S. pneumoniae
      infection. METHODS: Lung protein and messenger RNA levels were quantitated using
      Western blot and quantitative polymerase chain reaction. NFkB activation was
      measured by electrophoretic mobility shift assay. Cytokine levels were measured
      by cytometric bead analysis. To model chronic inflammation, mice were implanted
      with osmotic pumps that delivered tumor necrosis factor-alpha. RESULTS: Aged mice
      and those infused with tumor necrosis factor-alpha had increased levels of pIgR
      and PAFr in their lungs and were more susceptible to S. pneumoniae infection.
      During pneumonia, aged mice had reduced levels of pIgR and PAFr and less NFkB
      activation, despite greater bacterial burden. We determined that aged mice had
      decreased amounts of lung Toll-like receptors 1, 2, and 4 and reduced capacity to
      respond to S. pneumoniae with proinflammatory cytokine production. CONCLUSIONS:
      Aged mice and, potentially, elderly humans are more susceptible to pneumonia
      because of a priming effect of chronic inflammation and Toll-like receptor
      dysfunction.

PMID- 19586422
TI  - Endophthalmitis after intravitreal injections.
AB  - Endophthalmitis following intravitreal injection is an infrequent but serious
      clinical problem. Infectious endophthalmitis must be differentiated from
      noninfectious inflammation. Depending on the series, the risk of endophthalmitis
      is very low. The use of a standardized injection protocol can reduce the risk of
      infection.

PMID- 19586423
TI  - AZD-4818, a chemokine CCR1 antagonist: WO2008103126 and WO2009011653.
AB  - The applications WO2008103126 and WO2009011653, respectively, claim: i)
      Combinations of a spirocyclic piperidine chemokine CCR1 antagonist with a
      corticosteroid, and their use for the treatment of asthma and chronic obstructive
      pulmonary disease. ii) Processes for the preparation of a spirocyclic piperidine
      derivative, a chemokine CCR1 antagonist. These applications point to the
      preferred compound being a development compound. The evidence for this compound
      being AZD-4818, a chemokine CCR1 antagonist that was in Phase II development for
      the treatment of chronic obstructive pulmonary disease, is reviewed in the light
      of these and earlier patents relating to it.

PMID- 19586424
TI  - Sex differences in medical care after acute myocardial infarction: what can be
      done to address the problem?

PMID- 19586426
TI  - Screening for the early detection of ovarian cancer.

PMID- 19586427
TI  - Global cultural and socioeconomic factors that influence access to assisted
      reproductive technologies.
AB  - Assisted reproductive technology (ART) is the most successful treatment for the
      9% of people at reproductive age who suffer with infertility, but only a small
      percentage of those needing ART actually access it. Access varies greatly
      internationally owing to religious, cultural and political factors, probably the
      most important factor being each society's perspective on the moral status of the
      embryo. Economic factors, the nature of the healthcare system and public funding
      affect access both among and within countries. Regulations and guidelines are
      highly variable, but critical, in determining access and types of services. Cross
      border travel for reproductive care is not uncommon. In the future, better public
      funding of ART, technological improvements, lower cost and slow international
      harmonization with fewer differences in ART services will probably increase
      access significantly.

PMID- 19586428
TI  - Natural/mild assisted reproductive technologies: reducing cost and increasing
      safety.

PMID- 19586429
TI  - Advances in the treatment of menopausal symptoms.
AB  - Vasomotor symptoms and vaginal atrophy are both common menopausal symptoms.
      Hormone therapy is currently the only FDA-approved treatment for hot flashes.
      Current recommendations are to use the lowest dose of hormone therapy for the
      shortest period that will allow treatment goals to be met. Although the
      reanalysis of the WHI in 2007 by Roussow et al. provided evidence of coronary
      heart safety for users of hormone therapy under the age of 60 years and within 10
      years of the onset of menopause, not all women desire or are candidates for
      hormone therapy. In this review we present an evidence-based discussion
      considering the effectiveness of hormonal and nonhormonal therapies for the
      relief of vasomotor symptoms and vaginal atrophy. Concern exists regarding
      systemic absorption of vaginal estrogen and possible adverse effects on the
      breast and uterus. Selective estrogen receptor modulators and estrogen agonists
      offer benefits through targeted estrogen agonist/antagonistic effects and are
      being evaluated with and without estrogen for symptomatic menopausal women.
      Centrally acting nonhormonal therapies that are effective for the relief of
      vasomotor symptoms include various antidepressants, gabapentin and clonidine. A
      limited number of clinical trials have been conducted with nonprescription
      remedies, including paced respiration, yoga, acupuncture, exercise, homeopathy
      and magnet therapy, and some, but not all of these, have been found to be more
      effective than placebo. Dietary herbal supplements, such as soy and black cohosh,
      have demonstrated mixed and inconclusive results in placebo-controlled trials.
      Potential therapies for vasomotor symptoms and vaginal atrophy require
      randomized, placebo-controlled trials of sufficient duration to establish
      efficacy and safety. Agents under investigation for vasomotor symptoms relief
      include neuroactive agents, such as gabapentin and desvenlafaxine; an estrogen
      receptor-beta-targeted herbal therapy, MF-101; and the selective estrogen
      receptor modulator, bazedoxifene, paired with estrogen.

PMID- 19586430
TI  - Quality of sexual life and menopause.
AB  - The importance of female sexual fulfillment is increasingly recognized in today's
      society. Women's sexual lives continue well into the menopausal years and beyond;
      however, the impact of menopause on the quality of that sexual life has not been
      comprehensively studied in the medical literature. This review attempts to
      clarify the impact of the physiological, psychological and psychosocial changes
      occurring at midlife that may affect women's quality of sexual life.
      Pharmaceutical and psychological interventions that may assist in improving the
      quality of sexual life of menopausal women are discussed. Female sexuality is
      complex and not fully understood and, consequently, controversy frequently arises
      in the discussion of female sexual problems and their treatment. This article
      highlights some of these controversies and provides a future perspective on how
      the impact of menopause on the quality of sexual life may be more cohesively
      investigated.

PMID- 19586431
TI  - Paget's disease of the nipple.
AB  - Paget's disease of the nipple is an unusual epidermal presentation of underlying
      breast cancer. It presents as eczematous change or erythematous ulceration, but
      may also be an incidental histological finding in a mastectomy specimen.
      Approximately half of the underlying cancers are invasive, the remainder being
      ductal carcinoma in situ, and only rarely is there no associated malignancy.
      Routine clinical and mammographic assessment may significantly underestimate the
      extent of disease, but MRI may increase the sensitivity in detecting occult
      malignancy. Mastectomy maximizes local control; however, selected cases can be
      treated by nipple conisation with radiotherapy. Sentinel node biopsy is the
      standard of care for axillary staging in the clinically and ultrasonically node
      negative case. Almost all invasive cases overexpress human EGF receptor-2 and,
      therefore, are likely to benefit from adjuvant chemotherapy and herceptin.

PMID- 19586432
TI  - Cytoreductive surgery for advanced and recurrent endometrial cancer: a review of
      the literature.
AB  - There is no standard approach to managing women with advanced or recurrent
      endometrial cancer; however, there is increasing evidence to support a role for
      cytoreductive surgery in these women to improve survival outcome. The existing
      literature is limited by the inherent biases of retrospective studies, as well as
      small numbers of patients in individual studies; however, the association between
      optimal or complete cytoreductive surgery in patients with advanced and recurrent
      endometrial cancer and improved overall survival has been consistent.
      Furthermore, there is also a strong association between the size of postoperative
      residual disease and survival; as such, maximal cytoreduction should be the goal
      in carefully selected patients with advanced or recurrent endometrial cancer who
      are candidates for surgical management. Additional prospective research is needed
      in order to further define the role of cytoreductive surgery in advanced and
      recurrent endometrial cancer, and to develop effective adjuvant therapy to be
      used postoperatively in order to improve the prognosis in these women.

PMID- 19586434
TI  - Current perspectives in vulvodynia.
AB  - Vulvodynia, or chronic vulvar pain, is a common but poorly understood condition.
      Although its etiology is not well understood, it appears to be multifactorial. As
      such, treatment options are targeted to reduce singular symptoms in a piecemeal
      fashion. A number of randomized, controlled trials have been conducted and at
      least one paper on combination therapy has been published; however, further
      systematic research is needed in order to more fully inform clinical practice.

PMID- 19586435
TI  - Interventions for cardiovascular disease in women.
AB  - Cardiovascular disease represents the main health problem for women as it is the
      leading cause of death and morbidity. In recent years, technological advances and
      experience gained by surgeons and cardiologists has resulted in a significant
      improvement of percutaneous coronary procedures, which has been demonstrated to
      be safe and effective for both men and women. However, gender disparities in the
      management of coronary artery disease, specifically in the rate of use of these
      interventional procedures, as well as in the incidence of cardiovascular events
      have been reported. Treatment inequalities may also impact on outcomes. Possible
      reasons for treatment bias include a patient's preferences, a physician's
      decisions, biological and pathophysiological gender differences and inadequate
      evidence-based medicine among women.

PMID- 19586433
TI  - Management of uterine fibroids in the patient pursuing assisted reproductive
      technologies.
AB  - Uterine leiomyomas are present in 30-70% of women of reproductive age. In
      addition to causing menstrual disorders and pain, uterine fibroids negatively
      affect fertility and pregnancy outcome for patients pursuing assisted
      reproduction. The two questions that have to be addressed are: which fibroids
      should be treated and how should they be treated? Submucosal fibroids are
      associated with a 70% reduction in delivery rate. Intramural fibroids had a
      lesser effect and reduced the delivery rate by approximately 30%. By contrast,
      studies have demonstrated that subserosal fibroids did not negatively impact
      fertility. Furthermore, both submucosal and intramural fibroids were associated
      with an increased risk of spontaneous miscarriage. Myomectomy is considered the
      treatment of choice to alleviate these detrimental effects. Further research is
      needed before alternative treatments can be recommended.

PMID- 19586491
TI  - Iontophoretic delivery of lisinopril: Optimization of process variables by Box
      Behnken statistical design.
AB  - The objective of the investigation was to optimize the iontophoresis process
      parameters of lisinopril (LSP) by 3 x 3 factorial design, Box-Behnken statistical
      design. LSP is an ideal candidate for iontophoretic delivery to avoid the
      incomplete absorption problem associated after its oral administration.
      Independent variables selected were current (X(1)), salt (sodium chloride)
      concentration (X(2)) and medium/pH (X(3)). The dependent variables studied were
      amount of LSP permeated in 4 h (Y(1): Q(4)), 24 h (Y(2): Q(24)) and lag time
      (Y(3)). Mathematical equations and response surface plots were used to relate the
      dependent and independent variables. The regression equation generated for the
      iontophoretic permeation was Y(1) = 1.98 + 1.23X(1) - 0.49X(2) + 0.025X(3) -
      0.49X(1)X(2) + 0.040X(1)X(3) - 0.010X(2)X(3) + 0.58X(1)(2) - 0.17X(2)(2) -
      0.18X(3)(2); Y(2) = 7.28 + 3.32X(1) - 1.52X(2) + 0.22X(3) - 1.30X(1)X(2) +
      0.49X(1)X(3) - 0.090X(2)X(3) + 0.79X(1)(2) - 0.62X(2)(2) - 0.33X(3)(2) and Y(3) =
      0.60 + 0.0038X(1) + 0.12X(2) - 0.011X(3) + 0.005X(1)X(2) - 0.018X(1)X(3) -
      0.015X(2)X(3) - 0.00075X(1)(2) + 0.017X(2)(2) - 0.11X(3)(2). The statistical
      validity of the polynomials was established and optimized process parameters were
      selected by feasibility and grid search. Validation of the optimization study
      with 8 confirmatory runs indicated high degree of prognostic ability of response
      surface methodology. The use of Box-Behnken design approach helped in identifying
      the critical process parameters in the iontophoretic delivery of lisinopril.

PMID- 19586492
TI  - Design and evaluation of gastroretentive mucoadhesive cephalexin tablets.
AB  - The aim of this investigation was to develop gastroretentive mucoadhesive tablets
      of cephalexin, which will retain in the stomach for 10 h. Cephalexin, a first
      generation cephalosporin, becomes ionized in intestinal pH because pKa is 4.5 and
      thus reducing its bioavailability. The various batches were prepared by wet
      granulation method using variety of mucoadhesive polymers such as hydroxyl propyl
      methyl cellulose K4M, hydroxyl propyl cellulose, chitosan, carbopol 934P and
      sodium carboxymethylcellulose and subjected to various evaluation parameters such
      as mucoadhesive strength, in vitro drug release profile, swelling characteristics
      and physical properties. It was evident from the study that the formulation
      containing HPMC K4M and carbopol 934P in combination exhibited maximum
      mucoadhesive strength of 144.42 gms, in vitro residence time was 8.73 h and in
      vitro drug release was found to be 75.03% in 10 h with non-Fickian diffusion
      mechanism. So, the optimized formulation F(2) was further subjected to in vivo
      retention time in rabbit by X-ray technique, SEM and Accelerated stability
      studies. Regarding all the properties evaluated, the formulation containing HPMC
      K4M and carbopol 934P in combination was found to be the best to achieve the aim
      of this study.

PMID- 19586494
TI  - Differential expression of p63 isoforms in normal skin and hyperproliferative
      conditions.
AB  - BACKGROUND: The p63 is regarded as a potential stem cell marker. METHODS:
      Expression of p63 isoforms was examined in normal skin and hyperproliferative
      conditions including psoriasis and artificial skin equivalents (SEs). Rapidly
      adhering (RA) and slowly adhering (SA) cells were isolated, and Western blotting
      was performed. RESULTS: Expression of p63 (4A4) and p63 (H-137) is similar in all
      conditions, although there is some variation in psoriasis. However, expression of
      p63alpha (C-12) is markedly different. In normal skin, p63alpha (C-12)-positive
      cells were scattered in whole epidermis. But in psoriasis, p63alpha (C-12)
      positive cells were observed at the tips of rete ridges. In SEs, p63alpha (C-12)
      positive cells were not well observed. Western blot results showed that the RA
      cells express p63 (4A4) and p63 (H-137) strongly compared with SA or nonadhering
      (NA) cells. In contrast, SA or NA cells strongly express p63alpha (C-12).
      CONCLUSIONS: Results suggest that both p63 (4A4) and p63 (H-137) can detect
      epidermal stem cells. But, p63 (H-137) seemed to be a better marker because p63
      (H-137)-positive cells were more localized at basal layer. In addition, it can be
      said that p63alpha (C-12) can detect TAp63, which is important in differentiation
      of epidermis. Furthermore, it is concluded that molecular control of TAp63 is
      especially disorganized in hyperproliferative condition including psoriasis and
      SEs.

PMID- 19586495
TI  - Fulminant and accelerated presentation of dermatomyositis in two previously
      healthy young adult males: a potential role for endotheliotropic viral infection.
AB  - BACKGROUND: Dermatomyositis (DM) is a prototypic autoimmune syndrome, whereby
      immune-based microvascular injury is critical in the pathogenesis of skin lesions
      and the myopathy. Although not widely recognized or accepted as a pathogenetic
      trigger, endotheliotropic viral triggers including parvovirus B19 and
      cytomegalovirus have been linked to DM. At times, the clinical manifestations in
      DM can be fulminant with acute renal failure because of rhabdomyolysis,
      respiratory failure and gastrointestinal infarcts. METHODS: Skin and lung tissues
      were processed for hematoxylin and eosin, immunohistochemical, immunofluorescent
      and reverse transcriptase in situ polymerase chain reaction studies. CASE
      PRESENTATION: We present two cases of fatal DM in previously healthy
      immunocompetent males. One case had fatal catastrophic respiratory failure from
      diffuse alveolar damage; herpes simplex virus-2 RNA was uncovered in lung and
      skin biopsies during autopsy in the absence of classic cytopathic changes of
      herpes virus infection. The other case showed a Degos-like syndrome; parvovirus
      B19 RNA transcripts were found in cutaneous endothelium of affected skin.
      CONCLUSION: An accelerated clinical course can occur in the setting of DM in
      previously healthy patients. A viral-based etiology should be explored because
      antiviral therapy may define a critical and potentially lifesaving therapeutic
      endeavor.

PMID- 19586496
TI  - MPO-ANCA- and IgA-positive systemic vasculitis: a possibly overlapping syndrome
      of microscopic polyangiitis and Henoch-Schoenlein purpura.
AB  - Microscopic polyangiitis (MPA) can be distinguished from Henoch-Schoenlein
      purpura (HSP) based on the presence of renal-pulmonary complications,
      myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) seropositivity and
      pauci-immune glomerulonephritis; these characteristics of MPA are generally not
      found in HSP. Here, we present a unique case with MPA and HSP overlapping
      syndrome. A 74-year-old man presented with a skin rash accompanied by
      intracranial bleeding, acute renal failure and pulmonary hemorrhage resulting in
      a fatal outcome. An autopsy revealed the marked formation of crescentic
      glomerulonephritis, diffuse pulmonary alveolar hemorrhage and focal cerebral
      bleeding. Histological features showing both dermal small-vessel vasculitis and
      cutaneous polyarteritis nodosa-like arteritis suggested MPA rather than HSP, in
      which the dermal small vessels are exclusively affected. Meanwhile, capillary
      immunoglobulin (Ig)A deposits in the skin and glomeruli suggested HSP. As MPA and
      HSP overlapping syndrome characterized by the synergistic effect of MPO-ANCA and
      the IgA immune complex may result in a fatal outcome, aggressive
      immunosuppressive therapy should be initiated as early as possible.

PMID- 19586497
TI  - Imiquimod-induced vitiligo after treatment of nodular basal cell carcinoma.
AB  - An 84-year-old male presented with recurrent nodular infiltrative basal cell
      carcinoma on the left shoulder. The patient was treated with curettage followed
      by the application of topical imiquimod 5% cream five times a week. The patient
      discontinued imiquimod after a total of 18 applications because of local
      inflammation. Depigmentation was noted in the treated area 11 months after the
      initiation of treatment with imiquimod. The depigmented area did not resolve 14
      months after treatment initiation. Histologic examination of the depigmented area
      established the absence of melanin using Fontana-Masson stain and the absence of
      melanocytes using S-100 and Melan A stains. The adjacent unaffected skin showed a
      normal number of melanocytes and melanin pigment. To our knowledge, this is the
      first biopsy-proven case of vitiligo in an imiquimod-treated area.

PMID- 19586498
TI  - Apocrine mixed tumor of the skin with a prominent pilomatricomal component.
AB  - Pilomatrical differentiation within an apocrine mixed tumor (AMT) when present is
      only focal and has not been reported to be extensive. We herein report an AMT
      with prominent pilomatrical differentiation. A 47-year-old male presented with a
      0.7 cm lesion on the right eyebrow. Histologic sections revealed, underneath a
      neurofibroma, a well-circumscribed tumor composed of nodules of branching
      epithelial elements and occasional keratinous cysts within a myxoid and
      lipomatous stroma. The ductal structures appeared to be composed of two layers of
      basophilic cuboidal cells and exhibited decapitation secretion. In approximately
      50% of the tumor, eosinophilic ghost/shadow cells associated with a foreign body
      giant cell reaction formed a nodule resembling a pilomatricoma. Focally, columns
      of matrical cells were seen giving rise to shadow cells. Cytokeratin (CK) 5/6 and
      CK14 labeled the epithelial component. CK7, CK19 and Ber-EP4 labeled the ductal
      structures. Carcinoembryonic antigen and epithelial membrane antigen highlighted
      the luminal surface. S100 stained the stromal cells within the myxoid matrix,
      adipocytes and spindle cells within the overlying neurofibroma. CK10 highlighted
      the corneocytes within the keratinous cysts. CK17 labeled the epithelial lining
      of the keratinous cyst. The presence of follicular and apocrine differentiation
      within our tumor reinforces the common embryologic derivation of these elements.

PMID- 19586499
TI  - Castleman's disease with numerous mantle zone lymphocytes with clear cytoplasm
      involving the skin: case report.
AB  - Castleman's disease (CD) is an unusual lymphoid hyperplasia occurring in the
      mediastinal lymph nodes and, less frequently, in the neck lymph nodes. CD is
      classified clinically into a unicentric and a multicentric type, whereas three
      histomorphological variants are recognized: the hyaline vascular type, the
      intermediate type and the plasma cell type. We report the clinical and
      pathological features of a 54-year-old female suffering with multiple sclerosis
      and developing a lymph node hyaline-vascular type CD relapsing in the skin after
      24 months. Histological features showed a nodular dermatitis with atrophic
      germinal centers and an 'onion skin' rimming of lymphocytes in the mantle zone
      with numerous mantle zone lymphocytes with clear cytoplasm, with a CD20+, CD79a+,
      IgM+, IgG-, IgA-, CD5-, CD10-, CD43-, CD45RO-, bcl-2+ and bcl-6- phenotype with
      polytypic nature supporting the diagnosis of lymphoid variant of hyaline-vascular
      CD. This case shows that skin CD recapitulates all the histological variants of
      lymph node CD. Considering the many similarities between the present case and the
      primary cutaneous marginal zone lymphoma, it is important to bear in mind this
      atypical lymphoproliferative disorder in order to avoid overdiagnosis and
      overtreatment.

PMID- 19586500
TI  - Subcutaneous dirofilariasis caused by Dirofilaria repens in Greece: a case
      report.
AB  - Dirofilaria repens (formerly Dirofilaria conjunctiva) is a natural parasite of
      the subcutaneous tissues of dogs, cats and wild carnivores in Europe, Africa and
      Asia. Microfilariae are transmitted to humans by various species of mosquito. An
      autochthonous case of subcutaneous dirofilariasis is reported in a Greek patient
      from the island of Corfu. The clinical manifestation of the infection was a
      palpable, painless, subcutaneous nodule in the region of the groin, which 2 days
      before the patient consulted the doctor developed symptoms and signs of
      inflammation (pain, edema and redness). The entire lesion was surgically removed,
      and the nematode worm D. repens was identified on histological sections of biopsy
      material. The aim of this report was (a) to describe the microscopic
      morphological features of D. repens that enable identification of the parasite on
      histological examination and (b) to emphasize the importance of consideration of
      subcutaneous dirofilariasis in the differential diagnosis of subcutaneous nodules
      with inflammatory eosinophilic infiltration in countries where the infection is
      endemic.

PMID- 19586501
TI  - Cutaneous malignant peripheral nerve sheath tumors.
AB  - Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare entities
      compared with their deep soft tissue counterparts. We describe two cases of
      cutaneous MPNSTs. The first case, occurring in a 27-year-old woman with
      neurofibromatosis I, presented with recent growth of a pre-existing nodule on her
      back. A biopsy showed a densely cellular area within a conventional neurofibroma
      composed of atypical, hyperchromatic epithelioid and spindled cells with frequent
      mitotic figures (MFs). The second case presented in an 88-year-old man with no
      stigmata of neurofibromatosis as a rapidly growing subcutaneous tumor of the
      right calf. A biopsy showed a diffuse neurofibroma that abruptly transitioned to
      a densely cellular proliferation of hyperchromatic atypical spindled cells
      arranged in short fascicles with frequent MFs. The diagnosis of MPNST was
      rendered in both cases. MPNSTs of the dermis and subcutis are rare sarcomas. They
      can occur as sporadic tumors or in the setting of neurofibromatosis. They are
      often associated with pre-existing neurofibromas. Increase in size of pre
      existing neurofibromas is an indication for biopsy. Recognition of the cellular
      atypia, increased cellularity and mitotic activity is key to the diagnosis.

PMID- 19586502
TI  - Sweet's syndrome in familial Mediterranean fever: possible continuum of the
      neutrophilic reaction as a new cutaneous feature of FMF.
AB  - Sweet's syndrome (SS) or acute febrile neutrophilic dermatosis is an uncommon
      disorder that often occurs in association with other systemic diseases. In its
      systemic manifestation, SS resembles familial Mediterranean fever (FMF) in many
      aspects. Although the exact pathogenesis of SS and FMF is not yet clear, their
      clinical similarities and simultaneous occurrence suggest a possible common
      underlying mechanism and may represent a continuum of a reactive neutrophilic
      condition.

PMID- 19586504
TI  - Cutaneous Churg-Strauss granuloma in a child.

PMID- 19586503
TI  - Lymphedematous fibroepithelial polyps of the penis associated with long-term
      condom catheter use: case report and review of the literature.
AB  - Lymphedematous fibroepithelial polyps of the penis are lesions that have only
      recently been described and are frequently associated with condom catheter use.
      We report an additional case of lymphedematous fibroepithelial polyps of the
      penis in association with long-term condom catheter use in a 36-year-old man.
      Local excision showed large polypoid nodules with compact orthohyperkeratosis and
      mild acanthosis. The stroma was hypercellular with spindled to stellate
      fibroblasts and occasional multinucleated cells. Proliferation of small linear to
      slightly arcuate vessels with some superficial dilatation was a prominent
      feature. Focal expression of smooth muscle actin and desmin was present in the
      stroma. Lymphedematous fibroepithelial polyps of the penis are rare lesions with
      only 11 cases previously reported. We present here an additional example of this
      entity to highlight the differential diagnosis, the association with condom
      catheter use and to raise awareness for this unusual diagnosis.

PMID- 19586505
TI  - Sclerosing nevus with pseudomelanomatous features and regressing melanoma with
      nevoid features.

PMID- 19586507
TI  - Primary alopecia neoplastica versus secondary alopecia neoplastica: a new
      classification for neoplasm-associated scalp hair loss.

PMID- 19586508
TI  - Squamous cell carcinoma of the auricle with rhabdoid features.

PMID- 19586510
TI  - Merkel cell carcinoma: what is it, what will it do and where will it go? What
      role should the pathologist play in reporting this information?

PMID- 19586514
TI  - Effect of hair removal by Nd:YAG laser on the recurrence of pilonidal sinus.
AB  - BACKGROUND: Pilonidal sinus (PNS) is chronic inflammatory process of the skin in
      the natal cleft. Management of PNS is mainly surgical. Although different types
      of surgery have been performed, the recurrence rate is still high. OBJECTIVE: To
      evaluate the effectiveness of laser hair removal (LHR) in the natal cleft area on
      the recurrence rate of PNS as an adjuvant therapy after surgical treatment.
      METHODS: Twenty five patients with PNS were included in this study. Fifteen
      patients underwent LHR treatment using Nd:YAG laser after surgical excision of
      PNS (Patients group) while ten subjects with PNS did not do LHR and served as a
      control group. RESULTS: All of the patients were male patients. Their age ranged
      from 17 to 29 years with a mean of 21.60 +/- 3.13 years. They had Fitzpatrick
      skin type III, IV and V. The patients have got 3 to 8 sessions of LHR (mean 4.87
      +/- 1.64). Follow up period lasted between 12 to 23 months. None of the patients,
      who underwent LHR, has required further surgical treatment to date. Seven
      patients out of ten in the control group have developed recurrent PNS. Pain was
      the most frequent side effect and it was seen in 6 patients (40%). CONCLUSION:
      LHR can prevent the recurrence of PNS. LHR should be advised as an essential
      adjuvant treatment after surgical excision of PNS. In non-complicated recurrent
      PNS, LHR is strongly advocated to be started before and continued after doing
      surgical treatment.

PMID- 19586518
TI  - Abstracts of the 13th British Academic Conference in Otolaryngology and ENT Expo.
      July 8-10, 2009. Liverpool, United Kingdom.

PMID- 19586515
TI  - Isomorphic cutaneous graft-versus-host disease reaction after ultraviolet
      exposure: clinical, histological and direct immunofluorescence studies of four
      allo-transplanted patients.
AB  - BACKGROUND: Acute and chronic graft-versus-host disease (GVHD) continues to be a
      major limitation to successful haematopoietic stem cell transplantation. If
      experimental studies and clinical observations could partially elucidate the
      pathophysiology of acute GVHD, the biology of chronic GVHD is still much less
      well understood. OBJECTIVES: The aim of this study is to describe a peculiar
      photoinduced rash which triggered acute and then chronic lesions of GVHD in four
      allogenic haematopoietic-transplanted patients and discuss the possible aetiology
      and treatment. PATIENTS/METHODS: Four patients, two children and two adults
      affected by either mild or severe chronic GVHD, developed an erythematous rash on
      sun- or narrow-band ultraviolet B-exposed area, which triggered the onset of
      acute lesions of GVHD. Any of the patients presented neither a history of
      photosensitivity nor circulating autoantibodies nor urinary/fecal porphyrine.
      RESULTS: The histopathologic findings were characterized by an interface
      dermatitis with sparse perivascular infiltrate of lymphocytes and scattered
      necrotic keratinocytes, especially in the upper part of epidermis. Direct
      immunofluorescence studies excluded lupus-like pattern, revealing nests of
      fluorescent bodies at the dermal-epidermal junction and in papillary dermis.
      CONCLUSIONS: This peculiar isomorphic reaction of cutaneous GVHD after sun or
      narrow-band ultraviolet B exposures is described, and the possible mechanism
      involved is discussed. It may represent an interesting model of progression of
      chronic GVHD, starting with an acute stage and ending up with chronic clinical
      and histological findings, especially considering that there is no animal model
      that fully replicates all of the features of chronic GVHD in humans.

PMID- 19586522
TI  - Erythropoietin improves operant conditioning and stability of cognitive
      performance in mice.
AB  - BACKGROUND: Executive functions, learning and attention are imperative facets of
      cognitive performance, affected in many neuropsychiatric disorders. Recently, we
      have shown that recombinant human erythropoietin improves cognitive functions in
      patients with chronic schizophrenia, and that it leads in healthy mice to
      enhanced hippocampal long-term potentiation, an electrophysiological correlate of
      learning and memory. To create an experimental basis for further mechanistic
      insight into erythropoietin-modulated cognitive processes, we employed the Five
      Choice Serial Reaction Time Task. This procedure allows the study of the effects
      of erythropoietin on discrete processes of learning and attention in a sequential
      fashion. RESULTS: Male mice were treated for 3 weeks with erythropoietin (5,000
      IU/kg) versus placebo intraperitoneally every other day, beginning at postnatal
      day 28. After termination of treatment, mice were started on the Five Choice
      Serial Reaction Time Task, with daily training and testing extending to about 3
      months.Overall, a significantly higher proportion of erythropoietin-treated mice
      finished the task, that is, reached the criteria of adequately reacting to a 1.0
      sec flash light out of five arbitrarily appearing choices. During acquisition of
      this capability, that is, over almost all sequential training phases, learning
      readouts (magazine training, operant and discriminant learning, stability of
      performance) were superior in erythropoietin-treated versus control mice.
      CONCLUSION: Early erythropoietin treatment leads to lasting improvement of
      cognitive performance in healthy mice. This finding should be exploited in novel
      treatment strategies for brain diseases.

PMID- 19586524
TI  - Comparison of different methods to obtain and store liver biopsies for molecular
      and histological research.
AB  - BACKGROUND: To minimize the necessary number of biopsies for molecular and
      histological research we evaluated different sampling techniques, fixation
      methods, and storage procedures for canine liver tissue. For addressing the aim,
      three biopsy techniques (wedge biopsy, Menghini, True-cut), four storage methods
      for retrieval of RNA (snap freezing, RNAlater, Boonfix, RLT-buffer), two RNA
      isolation procedures (Trizol and RNAeasy), and three different fixation protocols
      for histological studies (10% buffered formalin, RNAlater, Boonfix) were
      compared. Histological evaluation was based on hematoxylin-eosin (HE) and
      reticulin (fibrogenesis) staining, and rubeanic acid and rhodanine stains for
      copper. Immunohistochemical evaluation was performed for cytokeratin-7 (K-7),
      multidrug resistance binding protein-2 (MRP-2) and Hepar-1. RESULTS: RNA quality
      was best guaranteed by the combination of a Menghini biopsy with NaCl, followed
      by RNAlater preservation and RNAeasy mini kit extraction. These results were
      confirmed by quantitative RT-PCR testing. Reliable histological assessment for
      copper proved only possible in formalin fixed liver tissue. Short formalin
      fixation (1-4 hrs) improved immunohistochemical reactivity and preservation of
      good morphology in small liver biopsies. CONCLUSION: At least two biopsies
      (RNAlater and formalin) are needed. Since human and canine liver diseases are
      highly comparable, it is conceivable that the protocols described here can be
      easily translated into the human biomedical field.

PMID- 19586523
TI  - Genome-wide analysis of interactions between ATP-dependent chromatin remodeling
      and histone modifications.
AB  - BACKGROUND: ATP-dependent chromatin remodeling and the covalent modification of
      histones play central roles in determining chromatin structure and function.
      Although several specific interactions between these two activities have been
      elaborated, the global landscape remains to be elucidated. RESULTS: In this
      paper, we have developed a computational method to generate the first genome-wide
      landscape of interactions between ATP-dependent chromatin remodeling and the
      covalent modification of histones in Saccharomyces cerevisiae. Our method
      succeeds in identifying known interactions and uncovers many previously unknown
      interactions between these two activities. Analysis of the genome-wide picture
      revealed that transcription-related modifications tend to interact with more
      chromatin remodelers. Our results also demonstrate that most chromatin remodeling
      modification interactions act via interactions of remodelers with both histone
      modifying enzymes and histone residues. We also found that the co-occurrence of
      both modification and remodeling has significantly different influences on
      multiple gene features (e.g. nucleosome occupancy) compared with the presence of
      either one. CONCLUSION: We gave the first genome-wide picture of ATP-dependent
      chromatin remodeling-histone modification interactions. We also revealed how
      these two activities work together to regulate chromatin structure and function.
      Our results suggest that distinct strategies for regulating chromatin activity
      are selectively employed by genes with different properties.

PMID- 19586525
TI  - Exon 6 of human JAG1 encodes a conserved structural unit.
AB  - BACKGROUND: Notch signaling drives developmental processes in all metazoans. The
      receptor binding region of the human Notch ligand Jagged-1 is made of a DSL
      (Delta/Serrate/Lag-2) domain and two atypical epidermal growth factor (EGF)
      repeats encoded by two exons, exon 5 and 6, which are out of phase with respect
      to the EGF domain boundaries. RESULTS: We determined the 1H-NMR solution
      structure of the polypeptide encoded by exon 6 of JAG1 and spanning the C
      terminal region of EGF1 and the entire EGF2. We show that this single,
      evolutionary conserved exon defines an autonomous structural unit that, despite
      the minimal structural context, closely matches the structure of the same region
      in the entire receptor binding module. CONCLUSION: In eukaryotic genomes, exon
      and domain boundaries usually coincide. We report a case study where this
      assertion does not hold, and show that the autonomously folding, structural unit
      is delimited by exon boundaries, rather than by predicted domain boundaries.

PMID- 19586526
TI  - A new multitest correction (SGoF) that increases its statistical power when
      increasing the number of tests.
AB  - BACKGROUND: The detection of true significant cases under multiple testing is
      becoming a fundamental issue when analyzing high-dimensional biological data.
      Unfortunately, known multitest adjustments reduce their statistical power as the
      number of tests increase. We propose a new multitest adjustment, based on a
      sequential goodness of fit metatest (SGoF), which increases its statistical power
      with the number of tests. The method is compared with Bonferroni and FDR-based
      alternatives by simulating a multitest context via two different kinds of tests:
      1) one-sample t-test, and 2) homogeneity G-test. RESULTS: It is shown that SGoF
      behaves especially well with small sample sizes when 1) the alternative
      hypothesis is weakly to moderately deviated from the null model, 2) there are
      widespread effects through the family of tests, and 3) the number of tests is
      large. CONCLUSION: Therefore, SGoF should become an important tool for multitest
      adjustment when working with high-dimensional biological data.

PMID- 19586527
TI  - HaMStR: profile hidden markov model based search for orthologs in ESTs.
AB  - BACKGROUND: EST sequencing is a versatile approach for rapidly gathering protein
      coding sequences. They provide direct access to an organism's gene repertoire
      bypassing the still error-prone procedure of gene prediction from genomic data.
      Therefore, ESTs are often the only source for biological sequence data from taxa
      outside mainstream interest. The widespread use of ESTs in evolutionary studies
      and particularly in molecular systematics studies is still hindered by the lack
      of efficient and reliable approaches for automated ortholog predictions in ESTs.
      Existing methods either depend on a known species tree or cannot cope with
      redundancy in EST data. RESULTS: We present a novel approach (HaMStR) to mine EST
      data for the presence of orthologs to a curated set of genes. HaMStR combines a
      profile Hidden Markov Model search and a subsequent BLAST search to extend
      existing ortholog cluster with sequences from further taxa. We show that the
      HaMStR results are consistent with those obtained with existing orthology
      prediction methods that require completely sequenced genomes. A case study on the
      phylogeny of 35 fungal taxa illustrates that HaMStR is well suited to compile
      informative data sets for phylogenomic studies from ESTs and protein sequence
      data. CONCLUSION: HaMStR extends in a standardized manner a pre-defined set of
      orthologs with ESTs from further taxa. In the same fashion HaMStR can be applied
      to protein sequence data, and thus provides a comprehensive approach to compile
      ortholog cluster from any protein coding data. The resulting orthology
      predictions serve as the data basis for a variety of evolutionary studies. Here,
      we have demonstrated the application of HaMStR in a molecular systematics study.
      However, we envision that studies tracing the evolutionary fate of individual
      genes or functional complexes of genes will greatly benefit from HaMStR orthology
      predictions as well.

PMID- 19586529
TI  - Risk factors for developing jumper's knee in sport and occupation: a review.
AB  - BACKGROUND: The onset of jumper's knee is generally associated with sports and
      sporting activities. Employees in certain professions might be at risk as well
      for developing jumper's knee. Therefore, it is of interest to identify risk
      factors in sport and/or occupation. FINDINGS: A systematic search of the
      international scientific literature was performed until November 2008 in the
      scientific databases (a) Medline, (b) Embase, and (c) SportDiscus. All types of
      studies were included. The search strategy retrieved ten articles about risk
      factors in sport that met the inclusion criteria. Risk factors that could be
      identified are; playing volleyball (4 studies), playing basketball (3 studies),
      training and playing volleyball/basketball more than 12 hours per week (2
      studies), in combination with weight-bearing activities of at least 5 hours per
      week (1 study) and playing or training on a hard surface (1 study). No studies
      were found regarding occupation that fulfilled the inclusion criteria.
      CONCLUSION: Playing volleyball and basketball has a positive association with the
      onset or worsening of jumper's knee. Other risk factors are training and playing
      hours of at least 12 hours per week and/or in combination with weight training of
      at least 5 hours per week, and/or with playing or training on a hard surface. We
      did not find a specific occupational risk factor.

PMID- 19586528
TI  - Non-SMC condensin I complex proteins control chromosome segregation and survival
      of proliferating cells in the zebrafish neural retina.
AB  - BACKGROUND: The condensation of chromosomes and correct sister chromatid
      segregation during cell division is an essential feature of all proliferative
      cells. Structural maintenance of chromosomes (SMC) and non-SMC proteins form the
      condensin I complex and regulate chromosome condensation and segregation during
      mitosis. However, due to the lack of appropriate mutants, the function of the
      condensin I complex during vertebrate development has not been described.
      RESULTS: Here, we report the positional cloning and detailed characterization of
      retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution
      live imaging reveals that the progression of mitosis between prometa- to
      telophase is delayed and that sister chromatid segregation is impaired upon loss
      of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the
      cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic
      mislocalization of CAP-G throughout mitosis. DNA content analysis reveals
      increased genomic imbalances upon loss of non-SMC condensin I subunits. Within
      the retina, loss of condensin I function causes increased rates of apoptosis
      among cells within the proliferative ciliary marginal zone (CMZ) whereas
      postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis
      partially rescues cell numbers in cap-g mutant retinae and allows normal layering
      of retinal cell types without alleviating their aberrant nuclear sizes.
      CONCLUSION: Our findings indicate that the condensin I complex is particularly
      important within rapidly amplifying progenitor cell populations to ensure
      faithful chromosome segregation. In contrast, differentiation of postmitotic
      retinal cells is not impaired upon polyploidization.

PMID- 19586530
TI  - Incidence of emergency contacts (red responses) to Norwegian emergency primary
      healthcare services in 2007--a prospective observational study.
AB  - BACKGROUND: The municipalities are responsible for the emergency primary health
      care services in Norway. These services include casualty clinics, primary doctors
      on-call and local emergency medical communication centres (LEMC). The National
      centre for emergency primary health care has initiated an enterprise called "The
      Watchtowers", comprising emergency primary health care districts, to provide
      routine information (patients' way of contact, level of urgency and first action
      taken by the out-of-hours services) over several years based on a minimal
      dataset. This will enable monitoring, evaluation and comparison of the respective
      activities in the emergency primary health care services. The aim of this study
      was to assess incidence of emergency contacts (potential life-threatening
      situations, red responses) to the emergency primary health care service. METHODS:
      A representative sample of Norwegian emergency primary health care districts,
      "The Watchtowers" recorded all contacts and first action taken during the year of
      2007. All the variables were continuously registered in a data program by the
      attending nurses and sent by email to the National Centre for Emergency Primary
      Health Care at a monthly basis. RESULTS: During 2007 the Watchtowers registered
      85 288 contacts, of which 1 946 (2.3%) were defined as emergency contacts (red
      responses), corresponding to a rate of 9 per 1 000 inhabitants per year. 65% of
      the instances were initiated by patient, next of kin or health personnel by
      calling local emergency medical communication centres or meeting directly at the
      casualty clinics. In 48% of the red responses, the first action taken was a call
      out of doctor and ambulance. On a national basis we can estimate approximately 42
      500 red responses per year in the EPH in Norway. CONCLUSION: The emergency
      primary health care services constitute an important part of the emergency system
      in Norway. Patients call the LEMC or meet directly at casualty clinics with
      medical problems that initially are classified as a potentially life-threatening
      situation, a red response.

PMID- 19586531
TI  - Tousled kinase TLK1B counteracts the effect of Asf1 in inhibition of histone H3
      H4 tetramer formation.
AB  - BACKGROUND: The Tousled-like kinases (TLKs) function in processes of chromatin
      assembly, including replication, transcription, repair, and chromosome
      segregation. TLK1 interacts specifically with the chromatin assembly factor Asf1,
      a histone H3-H4 chaperone, and with Rad9, a protein involved in DNA repair. Asf1
      binds to the H3-H4 dimer at the same interface that is used for formation of the
      core tetramer, and hence Asf1 is implicated in disruption of the tetramer during
      transcription, although Asf1 also has a function in chromatin assembly during
      replication and repair. FINDINGS: We have used protein crosslinking with purified
      components to probe the interaction between H3, H4, Asf1, and TLK1B. We found
      that TLK1B, by virtue of its binding to Asf1, can restore formation of H3-H4
      tetramers that is sterically prevented by adding Asf1. CONCLUSION: We suggest
      that TLK1B binds to Asf1 in a manner that interferes with its binding to the H3
      H4 dimer, thereby allowing for H3-H4 tetramerization. A description of the
      function of TLK1 and Asf1 in chromatin remodeling is presented.

PMID- 19586532
TI  - Experimental evaluation of insecticidal paints against Triatoma infestans
      (Hemiptera: Reduviidae), under natural climatic conditions.
AB  - BACKGROUND: Triatoma infestans is the main vector of Chagas disease in the Gran
      Chaco region of South America. The traditional spraying technique used for the
      application of pyrethroid insecticides has shown low efficiency in the
      elimination of the vector species populations occupying peridomestic structures
      of rural houses in the endemic area of Argentina. As part of studies looking for
      better alternatives, we evaluated the residual effect of insecticidal paints on
      the mortality of fourth instar nymphs of T. infestans. RESULTS: The study was
      based on an experimental design that included two groups treated with an
      organophosphate (Inesfly 5A IGR) and a pyrethroid (Inesfly 5A IGR NG)
      formulations of the paint, that were applied on wood, cement blocks and adobe
      bricks under natural climatic conditions. A third group was an untreated control.
      Both paint formulations showed very long residual activity, producing mortality
      of 84% and 98% (pyrethroid and organophosphate formulations, respectively) after
      12 months of the paint application. After eight months, nymphs exposed during 6
      hours to the painted surfaces with the pyrethroid and organophosphate
      formulations showed 81.33% and 100% mortality, respectively. CONCLUSION: The
      organophosphate- and pyrethroid-based insecticidal paints showed a very long
      residual activity on the mortality of fourth instar nymphs of T infestans,
      compared with the traditional spraying technique used for the application of
      pyrethroid insecticides in peridomestic structures of rural houses in the endemic
      region for Chagas disease in the Gran Chaco of Argentina. The application of the
      paints by trained personnel of the vector control programmes could be considered
      as an alternative control tool in areas where the traditional methods have failed
      or showed low efficacy.

PMID- 19586534
TI  - Correlates of local safety-related concerns in a Swedish Community: a cross
      sectional study.
AB  - BACKGROUND: Crime in a neighbourhood has been recognized as a key stressor in the
      residential environment. Fear of crime is related to risk assessment, which
      depends on the concentration of objective risk in time and space, and on the
      presence of subjective perceived early signs of imminent hazard. The aim of the
      study was to examine environmental, socio-demographic, and personal correlates of
      safety-related concerns at the local level in urban communities. The specific aim
      was to investigate such correlates in contiguous neighbourhoods in a Swedish
      urban municipality. METHODS: A cross-sectional study design was used to
      investigate three neighbourhood settings with two pair-wise conterminous but
      socially contrasting areas within each setting. Crime data were retrieved from
      police records. Study data were collected through a postal questionnaire
      distributed to adult residents (n = 2476) (response rate 56%). Composite
      dimensions of perceived residential safety were derived through a factor
      analysis. Logistic regression analysis was used to examine associations between
      high-level scores of the three safety-related dimensions and area-level crime
      rate, being a victim of crime, area reputation, gender, age, education, country
      of birth, household civil status and type of housing. RESULTS: Three composite
      dimensions of perceived residential safety were identified: (I) structural
      indicators of social disorder; (II) contact with disorderly behavior; and (III)
      existential insecurity. We found that area-level crime rates and individual-level
      variables were associated with the dimensions structural indicators of social
      disorder and existential insecurity, but only individual-level variables were
      associated with the dimension contact with disorderly behavior. Self-assessed
      less favorable area reputation was found to be strongly associated with all three
      factors. Being female accorded existential insecurity more than being a victim of
      crime. CONCLUSION: We have identified environmental, socio-demographic, and
      personal correlates of safety-related concerns in contiguous neighbourhoods in a
      Swedish community. The results of this study suggest that residents' self
      assessed area reputation is an important underlying mechanism of perceived
      safety. We also found a difference in crime rates and safety-related concerns
      between areas with blocks of flats compared with small-scale areas although the
      neighbourhoods were close geographically.

PMID- 19586533
TI  - Evidence for the association of the DAOA (G72) gene with schizophrenia and
      bipolar disorder but not for the association of the DAO gene with schizophrenia.
AB  - BACKGROUND: Previous linkage and association studies have implicated the D-amino
      acid oxidase activator gene (DAOA)/G30 locus or neighbouring region of chromosome
      13q33.2 in the genetic susceptibility to both schizophrenia and bipolar disorder.
      Four single nucleotide polymorphisms (SNPs) within the D-amino acid oxidase (DAO)
      gene located at 12q24.11 have also been found to show allelic association with
      schizophrenia. METHODS: We used the case control method to test for genetic
      association with variants at these loci in a sample of 431 patients with
      schizophrenia, 303 patients with bipolar disorder and 442 ancestrally matched
      supernormal controls all selected from the UK population. RESULTS: Ten SNPs
      spanning the DAOA locus were genotyped in these samples. In addition three SNPs
      were genotyped at the DAO locus in the schizophrenia sample. Allelic association
      was detected between the marker rs3918342 (M23), 3' to the DAOA gene and both
      schizophrenia (chi2 = 5.824 p = 0.016) and bipolar disorder (chi2 = 4.293 p =
      0.038). A trend towards association with schizophrenia was observed for two other
      DAOA markers rs3916967 (M14, chi2 = 3.675 p = 0.055) and rs1421292 (M24; chi2 =
      3.499 p = 0.062). A test of association between a three marker haplotype
      comprising of the SNPs rs778293 (M22), rs3918342 (M23) and rs1421292 (M24) and
      schizophrenia gave a global empirical significance of p = 0.015. No evidence was
      found to confirm the association of genetic markers at the DAO gene with
      schizophrenia. CONCLUSION: Our results provide some support for a role for DAOA
      in susceptibility to schizophrenia and bipolar disorder.

PMID- 19586535
TI  - Occurrence of hepatitis C virus infection in type 2 diabetic patients attending
      Plateau state specialist hospital Jos Nigeria.
AB  - BACKGROUND: Glucose intolerance is observed more in patients with HCV infection
      compared with control subjects with liver disease, Initial studies suggested that
      Hepatitis C virus infection may be an additional risk factor for the development
      of diabetes mellitus. This study was therefore carried out to determine the
      correlation of HCV infection and diabetes. METHODS: Three hundred (300) confirmed
      type 2 diabetic patients were screened for hepatitis C virus antibodies at the
      Plateau state specialist hospital, Jos, using Grand diagnostic test strip.
      Questionnaire comprising of age, sex, family history on diabetes, duration of
      disease and marital status were issued to subjects. RESULTS: Overall result
      showed that the prevalence rate of HCV infection was 33(11%). In response to
      diabetic status, females subjects had a higher prevalence of 178(59.3%) compared
      to males 122(40.7%). Those aged 47-57 recorded the highest seroprevalence
      10(30.3%) to the Hepatitis C Virus, while Patients without family history of
      diabetes showed a higher seroprevalence of 13(39.4%). Subjects who never had any
      blood transfusion recorded a prevalence rate of 6(18.2%). Marital status showed
      no significant difference [(P = 0.275; P.0.05)]. Considering duration of
      developing diabetes, patients within the range of 1-10 years diabetic status
      recorded the highest prevalence rate 25(75.8%) compared to other ranges
      considered. CONCLUSION: This study hence, suggests a relatively strong
      association between HCV infection and diabetes, this therefore call for an urgent
      approach strategy in the control and management of this disease of the endocrine
      system.

PMID- 19586536
TI  - Health - related quality of life of Kuwaiti women with breast cancer: a
      comparative study using the EORTC Quality of Life Questionnaire.
AB  - BACKGROUND: The Kuwaiti perspective on quality of life (QOL) in breast cancer is
      important because it adds the contribution from a country where the disease
      affects women at a relatively younger age and seems to be more aggressive. We
      used the EORTC QLQ - C30 and its breast-specific module (BR-23) to highlight the
      health-related QOL of Kuwaiti women with breast cancer, in comparison with the
      international data, and assessed the socio-demographic and clinical variables
      that predict the five functional scales and global QOL (GQOL) scale of the QLQ -
      C30. METHODS: Participants were consecutive clinic attendees for chemotherapy, in
      stable condition, at the Kuwait Cancer Control Center. RESULTS: The 348
      participants were aged 20-81 years (mean 48.3, SD 10.3); 58.7% had stages III and
      IV disease. Although the mean scores for QLQ - C30 (GQOL, 45.3; and five
      functional scales, 52.6%-61.2%) indicated that the patients had poor to average
      functioning, only 5.8% to 11.2% had scores that met the < or = 33% criterion for
      problematic functioning, while 12.0% to 40.0% met the >66% criterion for more
      severe symptoms. Most (47.8%-70.1%) met the >66% criterion for "good functioning"
      on the BR-23 functional scales. The mean scores of the QLQ - C30 indicated that,
      despite institutional supports, Kuwaiti women had clinically significantly poorer
      global QOL and functional scale scores, and more intense symptom experience, in
      comparison with the international data (i.e., < or = 10% difference between
      groups). For the BR-23, Kuwaiti women seemed to have clinically significantly
      better functional scale scores, but more severe symptoms, especially systemic
      side effects and breast symptoms. Younger women had poorer HRQOL scores. In
      regression analysis, social functioning accounted for the highest proportion of
      variance for GQOL. CONCLUSION: The relatively high number that met the criterion
      for good functioning on the functional scales is an evidence base to boost
      national health education about psychosocial prognosis in cancer. In view of the
      poor performance on the symptom scales, clinicians treating Kuwaiti women with
      breast cancer should prepare them for the acute toxicities of treatment and
      address fatigue. The findings call for the institution of a psycho-oncology
      service to address psycho-social issues.

PMID- 19586537
TI  - HCV genotyping using statistical classification approach.
AB  - The genotype of Hepatitis C Virus (HCV) strains is an important determinant of
      the severity and aggressiveness of liver infection as well as patient response to
      antiviral therapy. Fast and accurate determination of viral genotype could
      provide direction in the clinical management of patients with chronic HCV
      infections. Using publicly available HCV nucleotide sequences, we built a global
      Position Weight Matrix (PWM) for the HCV genome. Based on the PWM, a set of
      genotype specific nucleotide sequence "signatures" were selected from the 5' NCR,
      CORE, E1, and NS5B regions of the HCV genome. We evaluated the predictive power
      of these signatures for predicting the most common HCV genotypes and subtypes. We
      observed that nucleotide sequence signatures selected from NS5B and E1 regions
      generally demonstrated stronger discriminant power in differentiating major HCV
      genotypes and subtypes than that from 5' NCR and CORE regions. Two discriminant
      methods were used to build predictive models. Through 10 fold cross validation,
      over 99% prediction accuracy was achieved using both support vector machine (SVM)
      and random forest based classification methods in a dataset of 1134 sequences for
      NS5B and 947 sequences for E1. Prediction accuracy for each genotype is also
      reported.

PMID- 19586538
TI  - PRL-3 overexpression in epithelial cells is induced by surrounding stromal
      fibroblasts.
AB  - We isolate and culture carcinoma-associated fibroblasts (CAFs) from primary
      tumour (CAFpt), CAFs from corresponding synchronous liver metastasis (CAFlm) as
      well as normal colonic fibroblasts (NCF) from the same patient. From these
      cultures, conditioned media (CM) was obtained. Culture of a wide panel of
      colorectal and pancreatic cell lines in CM from CAFlm resulted in overexpression
      of mRNA PRL-3 and higher overexpression in CAFs than in non-activated
      fibroblasts. Moreover PRL-3 mRNA expression correlates with expression of alpha
      SMA and deposition of collagen fibrils in the stroma. We demonstrate that
      products secreted by CAFs trigger PRL-3 overexpression in cancer cells.
      Identification of these factors may contribute to new stroma-targeted therapies
      for desmoplastic tumours.

PMID- 19586539
TI  - Schwannoma of the larynx.
AB  - OBJECTIVES: Neurogenic tumors of the larynx are extremely rare. The goal of this
      report is to advert to this rare disease, to review and discuss diagnostics,
      differential diagnoses and treatment options. STUDY DESIGN: Retrospective case
      report and review of the literature. METHODS: Case report of a schwannoma of the
      supraglottic larynx and review of the English- and German-language literature
      regarding neurogenic tumors of the larynx. RESULTS: Neurogenic laryngeal tumors
      typically involve the supraglottic larynx, rarely the glottis. They can course
      globus sensation, dysphagia, dysphonia and upper airway obstruction. Imaging does
      not yield a definite diagnosis. The only curative treatment option is complete
      surgical resection. CONCLUSIONS: A definite diagnosis can only be made
      histologically. Endoscopic (laser-) resection for smaller lesions and external
      approaches for larger lesions are recommended treatment options.

PMID- 19586541
TI  - Morphogen-defined patterning of Escherichia coli enabled by an externally tunable
      band-pass filter.
AB  - BACKGROUND: Gradients of morphogens pattern cell fate - a phenomenon that is
      especially important during development. A simple model system for studying how
      morphogens pattern cell behavior would overcome difficulties inherent in the
      study of natural morphogens in vivo. A synthetic biology approach to building
      such a system is attractive. RESULTS: Using an externally-tunable band-pass
      filter paradigm, we engineered Escherichia coli cells to function as a model
      system for the study of how multiple morphogens can pattern cell behavior. We
      demonstrate how our system exhibits behavior such as morphogen crosstalk and how
      the cells' growth and fluorescence can be patterned in a number of complex
      patterns. We extend our cell patterning from 2D cultures on the surface of plates
      to 3D cultures in soft agarose medium. CONCLUSION: Our system offers a
      convenient, well-defined model system for fundamental studies on how multiple
      morphogen gradients can affect cell fate and lead to pattern formation. Our
      design principles could be applied to eukaryotic cells to develop other models
      systems for studying development or for enabling the patterning of cells for
      applications such as tissue engineering and biomaterials.

PMID- 19586540
TI  - Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes
      caused by expression of mutant huntingtin protein in striatal neurons.
AB  - BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder
      caused by a CAG repeat expansion mutation in the coding region of a novel gene.
      The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated
      aggregation associated with expression of mutant huntingtin protein (mhtt)
      contributes to the pathology. However, recent studies have identified early
      cellular dysfunctions that preclude aggregate formation. Suppression of
      aggregation is accepted as one of the markers of successful therapeutic
      approaches. Previously, we demonstrated that tricyclic pyrone (TP) compounds
      efficiently inhibited formation of amyloid-beta (Abeta) aggregates in cell and
      mouse models representing Alzheimer's Disease (AD). In the present study, we
      aimed to determine whether TP compounds could prevent aggregation and restore
      early cellular defects in primary embryonic striatal neurons from animal model
      representing HD. RESULTS: TP compounds effectively inhibit aggregation caused by
      mhtt in neurons and glial cells. Treatment with TP compounds also alleviated
      cholesterol accumulation and restored clathrin-independent endocytosis in HD
      neurons. CONCLUSION: We have found that TP compounds not only blocked mhtt
      induced aggregation, but also alleviated early cellular dysfunctions that
      preclude aggregate formation. Our data suggest TP molecules may be used as lead
      compounds for prevention or treatment of multiple neurodegenerative diseases
      including HD and AD.

PMID- 19586542
TI  - An MRI study on the relations between muscle atrophy, shoulder function and
      glenohumeral deformity in shoulders of children with obstetric brachial plexus
      injury.

PMID- 19586543
TI  - Non-invasive stroke volume measurement and passive leg raising predict volume
      responsiveness in medical ICU patients: an observational cohort study.
AB  - INTRODUCTION: The assessment of volume responsiveness and the decision to
      administer a fluid bolus is a common dilemma facing physicians caring for
      critically ill patients. Static markers of cardiac preload are poor predictors of
      volume responsiveness, and dynamic markers are often limited by the presence of
      spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR)
      represents an endogenous volume challenge that can be used to predict fluid
      responsiveness. METHODS: Medical intensive care unit (ICU) patients requiring
      volume expansion were eligible for enrollment. Non-invasive measurements of
      stroke volume (SV) were obtained before and during PLR using a transthoracic
      Doppler ultrasound device prior to volume expansion. Measurements were then
      repeated following volume challenge to classify patients as either volume
      responders or non-responders based on their hemodynamic response to volume
      expansion. The change in SV from baseline during PLR was then compared with the
      change in SV with volume expansion to determine the ability of PLR in conjunction
      with SV measurement to predict volume responsiveness. RESULTS: A total of 102
      fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges
      (46.1%), SV increased by > or =15% after volume infusion (responders). A SV
      increase induced by PLR of > or =15% predicted volume responsiveness with a
      sensitivity of 81%, specificity of 93%, positive predictive value of 91% and
      negative predictive value of 85%. CONCLUSIONS: Non-invasive SV measurement and
      PLR can predict fluid responsiveness in a broad population of medical ICU
      patients. Less than 50% of ICU patients given fluid boluses were volume
      responsive.

PMID- 19586544
TI  - Coordinated patterns of gene expressions for adult muscle build-up in transgenic
      mice expressing myostatin propeptide.
AB  - BACKGROUND: Skeletal muscle growth and maintenance are essential for human
      health. One of the muscle regulatory genes, namely myostatin, a member of
      transforming growth factor-beta, plays a dominant role in the genetic control of
      muscle mass. Myostatin is synthesized as a precursor protein, which generates the
      N-terminal propeptide and the C-terminal mature myostatin peptide by a post
      translational cleavage event. Previously, transgenic over-expression of myostatin
      propeptide in skeletal muscle results in significant muscle growth in early
      stages of development. The objectives of present study were to further
      characterize muscle growth in later stages of life and to identify genes and
      their expression patterns that are responsible for adult muscle build-up by
      myostatin propeptide. RESULTS: Immunohistochemical staining with an antibody to
      the N-terminus indicates a high level of myostatin propeptide present in the
      muscles of transgenic mice while there were no apparent differences in myostatin
      protein distribution in the muscle fibers between the transgenic and wild-type
      mice. Main individual muscles increased by 76-152% in the transgenic mice over
      their wild-type littermate mice at 12 months of age. A large number of nuclei
      were localized in the central and basal lamina of the myofibers in the transgenic
      mice as the number of nuclei per fiber and 100 microm(2) area was significantly
      higher in transgenic mice than wild-type mice. By systemic comparisons of global
      mRNA expression patterns between transgenic mice and wild-type littermates using
      microarray and qRT-PCR techniques, we have identified distinct gene expression
      patterns to support adult muscle build-up by myostatin propeptide, which are
      comprised of enhanced expressions of myogenic regulatory factors and
      extracelullar matrix components, and differentially down-regulated expressions of
      genes related to protein degradation and mitochondrial ATP synthesis. CONCLUSION:
      The results present a coordinated pattern of gene expressions for reduced energy
      utilization during muscle build-up in adult stage. Enhanced muscle buildup by
      myostatin propeptide is sustained by reduced ATP synthesis as a result of a
      decreased activity of protein degradation. Myostatin propeptide may have a
      therapeutic application to the treatment of clinical muscle wasting problems by
      depressing myostatin activity.

PMID- 19586545
TI  - Characterization of regulatory T cells in urban newborns.
AB  - BACKGROUND: In the United States, asthma prevalence is particularly high among
      urban children. Although the underlying immune mechanism contributing to asthma
      has not been identified, having impaired T regulatory (Treg) cells at birth may
      be a determining factor in urban children. The objective of this study was to
      compare Treg phenotype and function in cord blood (CB) of newborns to those in
      peripheral blood (PB) of a subset of participating mothers. METHODS: Treg
      numbers, expression, and suppressive function were quantified in subjects
      recruited prenatally from neighborhoods where >/= 20% of families have incomes
      below the poverty line. Proportion of Treg cells and expression of naive (CD45RA)
      or activated (CD45RO, CD69, and HLA-DR) markers in CD4+T cells was measured by
      flow cytometry. Treg suppressive capacity was determined by quantifying PHA
      stimulated lymphocyte proliferation in mononuclear cell samples with and without
      CD25 depletion. RESULTS: In an urban cohort of 119 newborns and 82 mothers, we
      found that newborns had similar number of cells expressing FOXP3 as compared to
      the mothers but had reduced numbers of CD4+CD25+bright cells that predominantly
      expressed the naive (CD45RA) rather than the activated/memory (CD45RO) phenotype
      found in the mothers. Additionally, the newborns had reduced mononuclear cell TGF
      beta production, and reduced Treg suppression of PHA-stimulated lymphocyte
      proliferation compared to the mothers. CONCLUSION: U.S. urban newborns have Treg
      cells that express FOXP3, albeit with an immature phenotype and function as
      compared to the mothers. Longitudinal follow-up is needed to delineate Treg cell
      maturation and subsequent risk for atopic diseases in this urban birth cohort.

PMID- 19586546
TI  - Effect of osteosynthesis, primary hemiarthroplasty, and non-surgical management
      for displaced four-part fractures of the proximal humerus in elderly: a multi
      centre, randomised clinical trial.
AB  - BACKGROUND: Fractures of the proximal humerus are common injuries and account for
      4-5 percent of all fractures, second only to hip and wrist fractures. The
      incidence is positively correlated with age and osteoporosis, and is likely to
      increase. Displaced four-part fractures are among the most severe injuries,
      accounting for 2-10 percent of proximal humeral fractures. The optimal
      intervention is disputed. Two previous randomised trials were very small and
      involved a noticeable risk of bias, and systematic reviews consequently conclude
      that there is inadequate basis for evidence-based treatment decisions. We aim to
      compare the effect of osteosynthesis with angle-stable plate with non-surgical
      management, and the effect of primary hemiarthroplasty with both osteosynthesis
      and non-surgical management. METHODS/DESIGN: We will conduct a randomised, multi
      centre, clinical trial including patients from ten national shoulder units within
      a two-year period. We plan to include 162 patients. A central randomisation unit
      will allocate patients. All patients will receive a standardised three-month
      rehabilitation program of supervised physiotherapy regardless of treatment
      allocation. Patients will be followed at least one year. The primary outcomes
      will be the overall score on the Constant Disability Scale, and its pain
      subscale, measured at 12 months. A blinded physiotherapist will carry out the
      assessments. Other secondary outcomes are Oxford Shoulder Score, and general
      health status (Short Form-36).

PMID- 19586547
TI  - Artificial arterial blood pressure artifact models and an evaluation of a robust
      blood pressure and heart rate estimator.
AB  - BACKGROUND: Within the intensive care unit (ICU), arterial blood pressure (ABP)
      is typically recorded at different (and sometimes uneven) sampling frequencies,
      and from different sensors, and is often corrupted by different artifacts and
      noise which are often non-Gaussian, nonlinear and nonstationary. Extracting
      robust parameters from such signals, and providing confidences in the estimates
      is therefore difficult and requires an adaptive filtering approach which accounts
      for artifact types. METHODS: Using a large ICU database, and over 6000 hours of
      simultaneously acquired electrocardiogram (ECG) and ABP waveforms sampled at 125
      Hz from a 437 patient subset, we documented six general types of ABP artifact. We
      describe a new ABP signal quality index (SQI), based upon the combination of two
      previously reported signal quality measures weighted together. One index measures
      morphological normality, and the other degradation due to noise. After extracting
      a 6084-hour subset of clean data using our SQI, we evaluated a new robust
      tracking algorithm for estimating blood pressure and heart rate (HR) based upon a
      Kalman Filter (KF) with an update sequence modified by the KF innovation sequence
      and the value of the SQI. In order to do this, we have created six novel models
      of different categories of artifacts that we have identified in our ABP waveform
      data. These artifact models were then injected into clean ABP waveforms in a
      controlled manner. Clinical blood pressure (systolic, mean and diastolic)
      estimates were then made from the ABP waveforms for both clean and corrupted
      data. The mean absolute error for systolic, mean and diastolic blood pressure was
      then calculated for different levels of artifact pollution to provide estimates
      of expected errors given a single value of the SQI. RESULTS: Our artifact models
      demonstrate that artifact types have differing effects on systolic, diastolic and
      mean ABP estimates. We show that, for most artifact types, diastolic ABP
      estimates are less noise-sensitive than mean ABP estimates, which in turn are
      more robust than systolic ABP estimates. We also show that our SQI can provide
      error bounds for both HR and ABP estimates. CONCLUSION: The KF/SQI-fusion method
      described in this article was shown to provide an accurate estimate of blood
      pressure and HR derived from the ABP waveform even in the presence of high levels
      of persistent noise and artifact, and during extreme bradycardia and tachycardia.
      Differences in error between artifact types, measurement sensors and the quality
      of the source signal can be factored into physiological estimation using an
      unbiased adaptive filter, signal innovation and signal quality measures.

PMID- 19586549
TI  - Exploring temporal transcription regulation structure of Aspergillus fumigatus in
      heat shock by state space model.
AB  - BACKGROUND: The thermotolerance of Aspergillus fumigatus plays a critical role in
      mammalian and avian infections. Thus, the identification of its adaptation
      mechanism to higher temperature is very important for an efficient anti-fungal
      drug development as well as fundamental understanding of its pathogenesis. We
      explored the temporal transcription regulation structure of this pathogenic
      fungus under heat shock conditions using the time series microarray data reported
      by Nierman et al. (Nature 2005, 438:1151-1156). RESULTS: The estimated
      transcription regulation structure of A. fumigatus shows that the heat shock
      proteins are strongly negatively associated with central metabolic pathway genes
      such as the tricarboxylic acid cycle (TCA cycle) and carbohydrate metabolism. It
      was 60 min and 120 min, respectively, after the growth temperature changes from
      30 degrees C (corresponding to environments of tropical soil) to 37 degrees C and
      48 degrees C (corresponding to temperatures in the human body and compost,
      respectively) that some of genes in TCA cycle were started to be upregulated. In
      these points, most of heat shock proteins showed lowest expression level after
      heat shocks. Among the heat shock proteins, the HSP30 (AFU6G06470), a single
      integral plasma membrane heat shock protein, presented most active role in
      transcription regulation structure in both heat shock conditions of 37 degrees C
      and 48 degrees C. The metabolic genes associated with multiple genes in the gene
      regulation network showed a tendency to have opposite expression patterns of heat
      shock proteins. The role of those metabolic genes was second regulator in the
      coherent feed-forward loop type of regulation structure having heat shock protein
      as its first regulator. This type of regulation structure might be very
      advantageous for the thermal adaptation of A. fumigatus under heat shock because
      a small amount of heat shock proteins can rapidly magnify their regulation effect
      on target genes. However, the coherent feed-forward loop type of regulation of
      heat shock proteins with metabolic genes became less frequent with increasing
      temperature. This might be the reason for dramatic increase in the expression of
      heat shock proteins and the number of heat shock response genes at heat shock of
      48 degrees C. CONCLUSION: We systemically analysed the thermal adaption mechanism
      of A. fumigatus by state space model with times series microarray data in terms
      of transcription regulation structure. We suggest for the first time that heat
      shock proteins might efficiently regulate metabolic genes using the coherent feed
      forward loop type of regulation structure. This type of regulation structure
      would also be efficient for adjustment to the other stresses requiring rapid
      change of metabolic mode as well as thermal adaptation.

PMID- 19586548
TI  - Effect of interleukin-1beta on spinal cord nociceptive transmission of normal and
      monoarthritic rats after disruption of glial function.
AB  - INTRODUCTION: Cytokines produced by spinal cord glia after peripheral injuries
      have a relevant role in the maintenance of pain states. Thus, while IL-1beta is
      overexpressed in the spinal cords of animals submitted to experimental arthritis
      and other chronic pain models, intrathecal administration of IL-1beta to healthy
      animals induces hyperalgesia and allodynia and enhances wind-up activity in
      dorsal horn neurons. METHODS: To investigate the functional contribution of glial
      cells in the spinal cord nociceptive transmission, the effect of intrathecally
      administered IL-1beta was studied in both normal and adjuvant-induced arthritic
      rats with or without glial inhibition. Four weeks after induction of
      monoarthritis, rats were treated with the glial cell inhibitor propentofylline
      (10 microg i.t. daily during 10 days) and submitted to a C-fiber-mediated reflex
      paradigm evoked by single and repetitive (wind-up) electric stimulation. RESULTS:
      Both the propentofylline treatment and the monoarthritic condition modified the
      stimulating current required for threshold activation of C reflex responses.
      Intrathecal IL-1beta increased spinal cord wind-up activity in normal and
      monoarthritic rats without propentofylline pre-treatment, but resulted in
      decreased wind-up activity in normal and monoarthritic propentofylline-treated
      animals. Intrathecal saline did not produce any effect. Thus, glial inactivation
      reverted into inhibition the excitatory effect of IL-1beta on spinal cord wind
      up, irrespective of the normal or monoarthritic condition of rats. CONCLUSIONS:
      The results suggest that the excitatory effect of nanomolar doses of IL-1beta on
      spinal wind-up in healthy rats is produced by an unidentified glial mediator,
      while the inhibitory effects of IL-1beta on wind-up activity in animals with
      inactivated glia resulted from a direct effect of the cytokine on dorsal horn
      neurons. The present study failed to demonstrate a differential sensitivity of
      normal and monoarthritic rats to IL-1beta administration into the spinal cord and
      to disruption of beta glial function, as both normal and monoarthritic animals
      changes wind-up activity in the same direction after propentofylline treatment,
      suggesting that after glial inhibition normal and monoarthritic animals behave
      similarly relative to the capability of dorsal horn neurons to generate wind-up
      activity when repeatedly stimulated by C-fibers.

PMID- 19586550
TI  - Increased mortality among survivors of myocardial infarction with kidney
      dysfunction: the contribution of gaps in the use of guideline-based therapies.
AB  - BACKGROUND: We assessed the degree to which differences in guideline-based
      medical therapy for acute myocardial infarction (AMI) contribute to the higher
      mortality associated with kidney disease. METHODS: In the PREMIER registry, we
      evaluated patients from 19 US centers surviving AMI. Cox regression evaluated the
      association between estimated glomerular filtration rate (GFR) and time to death
      over two years, adjusting for demographic and clinical variables. The
      contribution of variation in guideline-based medical therapy to differences in
      mortality was then assessed by evaluating the incremental change in the hazard
      ratios after further adjustment for therapy. RESULTS: Of 2426 patients, 26% had
      GFR > or = 90, 44% had GFR = 60- < 90, 22% had GFR = 30- < 60, and 8% had GFR <
      30 ml/min/1.73 m2. Greater degrees of renal dysfunction were associated with
      greater 2-year mortality and lower rates of guideline-based therapy among
      eligible patients. For patients with severely decreased GFR, adjustment for
      differences in guideline-based therapy did not significantly attenuate the
      relationship with mortality (HR 3.82, 95% CI 2.39-6.11 partially adjusted; HR =
      3.90, 95% CI 2.42-6.28 after adjustment for treatment differences). CONCLUSION:
      Higher mortality associated with reduced GFR after AMI is not accounted for by
      differences in treatment factors, underscoring the need for novel therapies
      specifically targeting the pathophysiological abnormalities associated with
      kidney dysfunction to improve survival.

PMID- 19586551
TI  - Functional annotations of diabetes nephropathy susceptibility loci through
      analysis of genome-wide renal gene expression in rat models of diabetes mellitus.
AB  - BACKGROUND: Hyperglycaemia in diabetes mellitus (DM) alters gene expression
      regulation in various organs and contributes to long term vascular and renal
      complications. We aimed to generate novel renal genome-wide gene transcription
      data in rat models of diabetes in order to test the responsiveness to
      hyperglycaemia and renal structural changes of positional candidate genes at
      selected diabetic nephropathy (DN) susceptibility loci. METHODS: Both Affymetrix
      and Illumina technologies were used to identify significant quantitative changes
      in the abundance of over 15,000 transcripts in kidney of models of spontaneous
      (genetically determined) mild hyperglycaemia and insulin resistance (Goto
      Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY
      rats injected with streptozotocin [STZ]). RESULTS: Different patterns of
      transcription regulation in the two rat models of diabetes likely underlie the
      roles of genetic variants and hyperglycaemia severity. The impact of prolonged
      hyperglycaemia on gene expression changes was more profound in STZ-WKY rats than
      in GK rats and involved largely different sets of genes. These included genes
      already tested in genetic studies of DN and a large number of protein coding
      sequences of unknown function which can be considered as functional and, when
      they map to DN loci, positional candidates for DN. Further expression analysis of
      rat orthologs of human DN positional candidate genes provided functional
      annotations of known and novel genes that are responsive to hyperglycaemia and
      may contribute to renal functional and/or structural alterations. CONCLUSION:
      Combining transcriptomics in animal models and comparative genomics provides
      important information to improve functional annotations of disease susceptibility
      loci in humans and experimental support for testing candidate genes in human
      genetics.

PMID- 19586552
TI  - Production of N-acetyl-D-neuraminic acid using two sequential enzymes
      overexpressed as double-tagged fusion proteins.
AB  - BACKGROUND: Two sequential enzymes in the production of sialic acids, N-acetyl-D
      glucosamine 2-epimerase (GlcNAc 2-epimerase) and N-acetyl-D-neuraminic acid
      aldolase (Neu5Ac aldolase), were overexpressed as double-tagged gene fusions.
      Both were tagged with glutathione S-transferase (GST) at the N-terminus, but at
      the C-terminus, one was tagged with five contiguous aspartate residues (5D), and
      the other with five contiguous arginine residues (5R). RESULTS: Both fusion
      proteins were overexpressed in Escherichia coli and retained enzymatic activity.
      The fusions were designed so their surfaces were charged under enzyme reaction
      conditions, which allowed isolation and immobilization in a single step, through
      a simple capture with either an anionic or a cationic exchanger (Sepharose Q or
      Sepharose SP) that electrostatically bound the 5D or 5R tag. The introduction of
      double tags only marginally altered the affinity of the enzymes for their
      substrates, and the double-tagged proteins were enzymatically active in both
      soluble and immobilized forms. Combined use of the fusion proteins led to the
      production of N-acetyl-D-neuraminic acid (Neu5Ac) from N-acetyl-D-glucosamine
      (GlcNAc). CONCLUSION: Double-tagged gene fusions were overexpressed to yield two
      enzymes that perform sequential steps in sialic acid synthesis. The proteins were
      easily immobilized via ionic tags onto ionic exchange resins and could thus be
      purified by direct capture from crude protein extracts. The immobilized, double
      tagged proteins were effective for one-pot enzymatic production of sialic acid.

PMID- 19586553
TI  - Integrin alpha6Bbeta4 inhibits colon cancer cell proliferation and c-Myc
      activity.
AB  - BACKGROUND: Integrins are known to be important contributors to cancer
      progression. We have previously shown that the integrin beta4 subunit is up
      regulated in primary colon cancer. Its partner, the integrin alpha6 subunit,
      exists as two different mRNA splice variants, alpha6A and alpha6B, that differ in
      their cytoplasmic domains but evidence for distinct biological functions of these
      alpha6 splice variants is still lacking. METHODS: In this work, we first analyzed
      the expression of integrin alpha6A and alpha6B at the protein and transcript
      levels in normal human colonic cells as well as colorectal adenocarcinoma cells
      from both primary tumors and established cell lines. Then, using forced
      expression experiments, we investigated the effect of alpha6A and alpha6B on the
      regulation of cell proliferation in a colon cancer cell line. RESULTS: Using
      variant-specific antibodies, we observed that alpha6A and alpha6B are
      differentially expressed both within the normal adult colonic epithelium and
      between normal and diseased colonic tissues. Proliferative cells located in the
      lower half of the glands were found to predominantly express alpha6A, while the
      differentiated and quiescent colonocytes in the upper half of the glands and
      surface epithelium expressed alpha6B. A relative decrease of alpha6B expression
      was also identified in primary colon tumors and adenocarcinoma cell lines
      suggesting that the alpha6A/alpha6B ratios may be linked to the proliferative
      status of colonic cells. Additional studies in colon cancer cells showed that
      experimentally restoring the alpha6A/alpha6B balance in favor of alpha6B caused a
      decrease in cellular S-phase entry and repressed the activity of c-Myc.
      CONCLUSION: The findings that the alpha6Bbeta4 integrin is expressed in quiescent
      normal colonic cells and is significantly down-regulated in colon cancer cells
      relative to its alpha6Abeta4 counterpart are consistent with the anti
      proliferative influence and inhibitory effect on c-Myc activity identified for
      this alpha6Bbeta4 integrin. Taken together, these findings point out the
      importance of integrin variant expression in colon cancer cell biology.

PMID- 19586554
TI  - Downregulation of SFRP5 expression and its inverse correlation with those of MMP
      7 and MT1-MMP in gastric cancer.
AB  - BACKGROUND: As negative regulators in Wnt signaling, Secreted Frizzled-Related
      Proteins (SFRPs) are downregulated in a series of human cancers; and
      specifically, some matrix metalloproteinases (MMPs), including MMP-2, MMP-7, MMP
      9 and MT1-MMP, are frequently overexpressed in gastric cancer. The aim of this
      study is to determine the expression status of SFRP5 in gastric cancer and
      explore the correlation between both the expression of SFRP5 and that of these
      MMPs in this cancer. METHODS: Expression of SFRP5, MMP-2, MMP-7, MMP-9 and MT1
      MMP was determined by real-time PCR, RT-PCR or Western blotting. The methylation
      status of SFRP5 was detected by Methylation-specific PCR (MSP). Cell lines with
      SFRP5 methylation were demethylated by a DNA methyltransferase inhibitor 5-Aza-2'
      deoxycytidine (DAC). KatoIII cells were transfected with pcDNA3.1 SFRP5 vector to
      strengthen SFRP5 expression. To abrogate SFRP5 expression in MKN1 cells, SFRP5
      RNAi plamid was used to transfect them. RESULTS: SFRP5 expression was remarkably
      downregulated in 24 of 32 primary gastric cancer specimens, and even was not
      detectable in 5 of 8 gastric cancer cell lines. MMP-7 and MT1-MMP mRNA showed a
      stronger expression in these 24 specimens compared to the other 8 specimens. They
      also showed higher levels in gastric cancer cell lines AGS and NCI-N87 which had
      no SFRP5 expression, compared to MKN1 with strong SFRP5 expression. However, they
      were significantly downregulated, with SFRP5 expression restored in AGS and NCI
      N87; and were considerably upregulated with it abrogated in MKN1. CONCLUSION: The
      results indicate there are frequent occurrences of downregualtion of SFRP5
      expression in gastric cancer, primarily due to SFRP5 methylation. It seems to be
      responsible for the upregulation of MMP-7 expression and MT1-MMP expression on
      the ground that they are inversely correlated with SFRP5 expression.

PMID- 19586555
TI  - Complex coevolutionary history of symbiotic Bacteroidales bacteria of various
      protists in the gut of termites.
AB  - BACKGROUND: The microbial community in the gut of termites is responsible for the
      efficient decomposition of recalcitrant lignocellulose. Prominent features of
      this community are its complexity and the associations of prokaryotes with the
      cells of cellulolytic flagellated protists. Bacteria in the order Bacteroidales
      are involved in associations with a wide variety of gut protist species as either
      intracellular endosymbionts or surface-attached ectosymbionts. In particular,
      ectosymbionts exhibit distinct morphological patterns of the associations.
      Therefore, these Bacteroidales symbionts provide an opportunity to investigate
      not only the coevolutionary relationships with the host protists and their
      morphological evolution but also how symbiotic associations between prokaryotes
      and eukaryotes occur and evolve within a complex symbiotic community. RESULTS:
      Molecular phylogeny of 31 taxa of Bacteroidales symbionts from 17 protist genera
      in 10 families was examined based on 16S rRNA gene sequences. Their localization,
      morphology, and specificity were also examined by fluorescent in situ
      hybridizations. Although a monophyletic grouping of the ectosymbionts occurred in
      three related protist families, the symbionts of different protist genera were
      usually dispersed among several phylogenetic clusters unique to termite-gut
      bacteria. Similar morphologies of the associations occurred in multiple lineages
      of the symbionts. Nevertheless, the symbionts of congeneric protist species were
      closely related to one another, and in most cases, each host species harbored a
      unique Bacteroidales species. The endosymbionts were distantly related to the
      ectosymbionts examined so far. CONCLUSION: The coevolutionary history of gut
      protists and their associated Bacteroidales symbionts is complex. We suggest
      multiple independent acquisitions of the Bacteroidales symbionts by different
      protist genera from a pool of diverse bacteria in the gut community. In this
      sense, the gut could serve as a reservoir of diverse bacteria for associations
      with the protist cells. The similar morphologies are considered a result of
      evolutionary convergence. Despite the complicated evolutionary history, the host
      symbiont relationships are mutually specific, suggesting their cospeciations at
      the protist genus level with only occasional replacements.

PMID- 19586556
TI  - Efficacy of consensus interferon in treatment of HbeAg-positive chronic hepatitis
      B: a multicentre, randomized controlled trial.
AB  - BACKGROUND: Consensus interferon (CIFN) is a newly developed type I interferon.
      AIMS: This multicentre, controlled trial was conducted to determine the efficacy
      of CIFN and to compare it with alpha-1b-interferon (IFN-alpha1b) in the treatment
      of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
      METHODS: 144 Patients were randomly assigned to receive 9 microg CIFN (CIFN
      group) or 50 microg INF-alpha1b (IFN-alpha group) subcutaneously 3 times weekly
      for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by
      normalization of serum alanine transaminase (ALT) levels and the non
      detectability of serum hepatitis B virus DNA or HBeAg at the end of treatment and
      24 weeks after stopping treatment. RESULTS: There was no statistically
      significant difference in the serological, virological and biochemical parameters
      between CIFN and IFN-alpha1b groups at the end of the therapy and follow-up
      period (p > 0.05). Overall, at the end of treatment, 7.0% (5/71) and 35.2%
      (25/71) of patients in the CIFN group showed a complete or partial response
      compared with 7.4% (5/68) and 33.8% (23/68) of the IFN-alpha group (p = 0.10). At
      24 weeks after stopping treatment, 6.9% (5/72) and 37.5% (27/72) of patients in
      the CIFN group showed complete response or partial response compared with 7.1%
      (5/70) and 34.3% (24/70) of the IFN-alpha group (p = 0.10). CONCLUSION: These
      findings suggest that 9 microg CIFN is effective in the treatment of patients
      with HBeAg-positive chronic hepatitis B. It can gradually induce ALT
      normalization and HBV DNA clearance and HBeAg loss or HBeAg/HBeAb seroconversion.

PMID- 19586557
TI  - Stem cell therapy for cardiac repair: benefits and barriers.
AB  - Cardiovascular disease remains the leading cause of death worldwide. Acute
      ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac
      tissue and ultimately heart failure. Current therapies aim largely to attenuate
      the pathological remodelling that occurs after injury and to reduce risk factors
      for cardiovascular disease. Studies in animal models indicate that
      transplantation of mesenchymal stem cells, bone-marrow-derived haematopoietic
      stem cells, skeletal myoblasts, or embryonic stem cells has the potential to
      improve the function of ventricular muscle after ischaemic injury. Clinical
      trials using primarily bone-marrow-derived cells and skeletal myoblasts have also
      produced some encouraging results. However, the current experimental evidence
      suggests that the benefits of cell therapy are modest, the generation of new
      cardiac tissue is low, and the predominant mechanisms of action of transplanted
      stem cells involve favourable paracrine effects on injured myocardium. Recent
      studies show that the adult heart possesses various pools of putative resident
      stem cells, raising the hope that these cells can be isolated for therapy or
      manipulated in vivo to improve the healing of cardiac muscle after injury. This
      article reviews the properties and potential of the various stem cell populations
      for cardiac repair and regeneration as well as the barriers that might lie ahead.

PMID- 19586559
TI  - Effects of IAA in combination with FSH on in vitro culture of ovine preantral
      follicles.
AB  - Ovarian cortical fragments from five adult ewes were in vitro cultured for 1, 3
      or 5 days in the presence of minimum essential medium either supplemented or not
      by follicle-stimulating hormone (FSH) (100 ng/ml) or indole-3-acetic acid (IAA)
      (10, 20, 40 or 100 ng/ml), alone or in combination. After in vitro culture,
      ovarian fragments were submitted to follicular isolation and viability test was
      performed using trypan blue. Addition of IAA (10 ng/ml) to a free-FSH medium
      resulted in the highest percentages of viable follicles, but was progressively
      deleterious in higher concentrations (20, 40 and 100 ng/ml) if in absence of FSH.
      Follicular development was observed only when FSH was added to an IAA-free
      medium. In conclusion, IAA at a concentration of 10 ng/ml increases follicular
      survival in vitro. However, at high concentrations (20, 40 or 100 ng/ml), this
      auxin may be deleterious to preantral follicles, the addition of FSH to the
      medium being necessary.

PMID- 19586558
TI  - Inflammatory disease processes and interactions with nutrition.
AB  - Inflammation is a stereotypical physiological response to infections and tissue
      injury; it initiates pathogen killing as well as tissue repair processes and
      helps to restore homeostasis at infected or damaged sites. Acute inflammatory
      reactions are usually self-limiting and resolve rapidly, due to the involvement
      of negative feedback mechanisms. Thus, regulated inflammatory responses are
      essential to remain healthy and maintain homeostasis. However, inflammatory
      responses that fail to regulate themselves can become chronic and contribute to
      the perpetuation and progression of disease. Characteristics typical of chronic
      inflammatory responses underlying the pathophysiology of several disorders
      include loss of barrier function, responsiveness to a normally benign stimulus,
      infiltration of inflammatory cells into compartments where they are not normally
      found in such high numbers, and overproduction of oxidants, cytokines,
      chemokines, eicosanoids and matrix metalloproteinases. The levels of these
      mediators amplify the inflammatory response, are destructive and contribute to
      the clinical symptoms. Various dietary components including long chain omega-3
      fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics
      have the potential to modulate predisposition to chronic inflammatory conditions
      and may have a role in their therapy. These components act through a variety of
      mechanisms including decreasing inflammatory mediator production through effects
      on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant
      flavonoids), reducing the production of damaging oxidants (vitamin E and other
      antioxidants), and promoting gut barrier function and anti-inflammatory responses
      (prebiotics and probiotics). However, in general really strong evidence of
      benefit to human health through anti-inflammatory actions is lacking for most of
      these dietary components. Thus, further studies addressing efficacy in humans
      linked to studies providing greater understanding of the mechanisms of action
      involved are required.

PMID- 19586560
TI  - Fine structural observation on the oogenesis and vitellogenesis of the Chinese
      soft-shelled turtle ( Pelodiseus sinensis).
AB  - Fine structure observations were performed by means of electron microscopy on
      oogenesis and vitellogenesis and the special functions of follicular cells in the
      Chinese soft-shelled turtle (Pelodiseus sinensis). Histological examination of
      the ovary showed a well developed lacunae system containing fine granules, fibres
      or gelatiniform materials with one or two germinal beds dispersed on the dorsal
      surface of the ovarian cortex. The process of oogenesis comprised 10 consecutive
      phases according to the morphology of the yolk platelets, follicular cells and
      zona pellucida (ZP). Electron microscopy of vitellogenesis revealed some of the
      mitochondria gradually being transformed into yolk granules. In the advanced
      stage of vitellogenesis, large amounts of rough endoplasmic reticula, Golgiosomes
      and other cell organelles that are involved in synthesis and secretion were
      observed in follicular cells. The ZP was formed by microvilli, thus increasing
      the absorptive surface of the oocyte and facilitating transport of nutrients from
      the follicular epithelium to the ooplasm. This study demonstrated that the
      ovaries of members of the Testudinidae share more features with Archosaurs than
      with Squamates, indicating that these features were phylogenetically conserved in
      the Archosauria. The present observations suggest that the accumulation of yolk
      materials was controlled by the intrinsic and extrinsic pathways as well as by
      the activity of follicular cells. These results might also support a sibling
      relationship of the Testudinidae with the Archosauria and not with all extant
      reptiles.

PMID- 19586561
TI  - Polymorphisms of the estrogen receptor alpha (ESR1) gene and the risk of
      Alzheimer's disease in a southern Chinese community.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease with a higher
      prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been
      identified throughout the brain. Owing to the putative neuroprotective effects of
      estrogen, estrogen receptor gene is a potential candidate modulating the
      development of AD. Preliminary associations between two polymorphisms of ESR1
      (PvuII and XbaI) gene and AD have been reported. METHODS: In this study, 16
      single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly
      studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database)
      were investigated to further evaluate the association between ESR1 polymorphisms
      and the risk of AD in the Chinese population. RESULTS: A total of 233 Chinese AD
      patients and 245 age-matched elderly control subjects were recruited. Genetic
      associations were analyzed by chi-square test and interaction effect was analysed
      by logistic regression analysis. Five SNPs (clustered between intron 3 and intron
      7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035);
      another two SNPs (located on exon 2 and intron 2) were shown to modulate the age
      at-onset (AAO) in AD (p-value = 0.036 and 0.011). CONCLUSIONS: ESR1 gene
      polymorphisms may be associated with the AAO in AD. The present results provided
      information for possible associations between certain polymorphisms of ESR1 gene
      and the risk of AD.

PMID- 19586562
TI  - Research on treating neuropsychiatric symptoms of advanced dementia with non
      pharmacological strategies, 1998-2008: a systematic literature review.
AB  - BACKGROUND: Advanced dementia is characterized by severe cognitive and functional
      impairments that lead to almost total dependency in self-care. Neuropsychiatric
      symptoms (NPS) are common in advanced dementia, diminishing quality of life and
      increasing the care burden. The challenge for health care providers is to find
      safe and effective treatments. Non-pharmacological interventions offer the
      potential for safer alternatives to pharmacotherapy, but little is known about
      their efficacy. This review evaluates the published literature on non
      pharmacological interventions for treating NPS in advanced dementia. METHODS: A
      literature search was undertaken to find non-pharmacological intervention studies
      published between 1998 and 2008 that measured NPS outcomes in individuals
      diagnosed with advanced dementia. Strict inclusion criteria initially required
      that all study participants have severe or very severe dementia, but this range
      was later broadened to include moderately severe to very severe stages. RESULTS:
      Out of 215 intervention studies, 21 (9.8%) specifically focused on treatments for
      individuals with moderately severe to very severe dementia. The studies provide
      limited moderate to high quality evidence for the use of sensory-focused
      strategies, including aroma, preferred or live music, and multi-sensory
      stimulation. Emotion-oriented approaches, such as simulated presence may be more
      effective for individuals with preserved verbal interactive capacity.
      CONCLUSIONS: Most studies of interventions for dementia-related NPS have focused
      on individuals with mild to moderate cognitive impairment. Individuals with
      severe cognitive impairment do not necessarily respond to NPS treatments in the
      same manner. Future studies should be specifically designed to further explore
      the stage-specific efficacy of non-pharmacological therapies for patients with
      advanced dementia. Areas of particular need for further research include movement
      based therapies, hands-on (touch) therapies, and interventions that can be
      provided during personal care routines. Interventions appear to work best when
      they are tailored to balance individual arousal patterns.

PMID- 19586564
TI  - Premorbid personality traits are associated with post-stroke behavioral and
      psychological symptoms: a three-month follow-up study in Perth, Western
      Australia.
AB  - BACKGROUND: Previous research has found an association between post-stroke
      depressive symptoms and premorbid personality. This study sought to investigate
      further the relationship between premorbid personality and a number of common
      post-stroke behavioral and psychological symptoms in a three-month follow-up
      study. METHODS: This prospective study was conducted between May 2003 and January
      2005 in a Perth metropolitan teaching hospital. The pre-stroke personality of
      stroke survivors was assessed by interviewing a close family member (informant)
      within four weeks of the index stroke using the NEO Personality Inventory
      Revised. Three months after the stroke, patients were followed up and assessed
      with the Cambridge Cognitive examination and Hospital Anxiety and Depression
      Scale, and their informants completed the Neuropsychiatric Inventory-carer
      distress version (NPI) and instrumental activities of daily living scale.
      RESULTS: Depressive symptoms were the most commonly reported post-stroke symptom
      (45.1%). Spearman's correlations showed that high neuroticism was positively
      correlated with NPI total scores (rho = 0.37, p = 0.007), NPI total distress
      scores (rho = 0.47, p = 0.001), and specifically with agitation and irritability
      NPI composite scores. Agreeableness was inversely correlated with agitation (rho
      = -0.40, p = 0.004) and irritability (rho = -0.37, p = 0.007) composite scores.
      CONCLUSIONS: Premorbid personality traits of high neuroticism and low
      agreeableness are associated with the presence of post-stroke agitation,
      irritability, and carer distress. This knowledge may contribute to the
      development of strategies designed to identify patients and families who require
      more intense supervision and support during post-stroke rehabilitation.

PMID- 19586563
TI  - Effects of age, gender, education and race on two tests of language ability in
      community-based older adults.
AB  - BACKGROUND: Neuropsychological tests, including tests of language ability, are
      frequently used to differentiate normal from pathological cognitive aging.
      However, language can be particularly difficult to assess in a standardized
      manner in cross-cultural studies and in patients from different educational and
      cultural backgrounds. This study examined the effects of age, gender, education
      and race on performance of two language tests: the animal fluency task (AFT) and
      the Indiana University Token Test (IUTT). We report population-based normative
      data on these tests from two combined ethnically divergent, cognitively normal,
      representative population samples of older adults. METHODS: Participants aged >
      or =65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) and
      from the Indianapolis Study of Health and Aging (ISHA) were selected based on (1)
      a Clinical Dementia Rating (CDR) score of 0; (2) non-missing baseline language
      test data; and (3) race self-reported as African-American or white. The combined
      sample (n = 1885) was 28.1% African-American. Multivariate ordinal logistic
      regression was used to model the effects of demographic characteristics on test
      scores. RESULTS: On both language tests, better performance was significantly
      associated with higher education, younger age, and white race. On the IUTT,
      better performance was also associated with female gender. We found no
      significant interactions between age and sex, and between race and education.
      CONCLUSIONS: Age and education are more potent variables than are race and gender
      influencing performance on these language tests. Demographically stratified
      normative tables for these measures can be used to guide test interpretation and
      aid clinical diagnosis of impaired cognition.

PMID- 19586565
TI  - Perceptions of self-stigma and its correlates among older adults with depression:
      a preliminary study.
AB  - BACKGROUND: Depression is common in old age and is often associated with stigma.
      However, to date, little is known about self-stigma (internalization of stigmatic
      beliefs) in depressed older people despite its importance and consequences. The
      aim of this study was to examine self-stigma and its correlates in depressed
      older people. METHODS: Phone interviews were conducted with 54 persons diagnosed
      with major depression (78% female, average age = 74) from a psychogeriatric
      clinic in the central area of Israel. Self-stigma was assessed using an adapted
      version of the Internalized Stigma of Mental Health (ISMI) scale. Symptoms of
      depression were assessed using the short form of the Geriatric Depression Scale
      (GDS). Self-esteem was measured using Rosenberg's Self Esteem Scale. Information
      regarding sociodemographic and psychiatric health characteristics was also
      collected. RESULTS: Self-stigma was relatively moderate with 10% to 20% of the
      participants reporting self-stigma. Those who reported higher levels of self
      stigma were younger than those who did not report it. Income and education were
      lower in persons who reported high levels of stigmatization. Persons who reported
      stigmatization scored higher on the GDS and reported lower self-esteem than those
      without stigmatization. CONCLUSIONS: This study represents an effort to examine
      the correlates of self-stigma in depressed older people. Since self-stigma exists
      among older adults, further studies are required to extend this body of
      knowledge.

PMID- 19586567
TI  - Influence of long-term consumption of a Lactococcus lactis strain on the
      intestinal immunity and intestinal flora of the senescence-accelerated mouse.
AB  - The senescence-accelerated mouse develops normally until 5-6 months of age and
      then displays rapid and irreversible advancement of senescence manifesting as
      clinical signs and gross lesions. To clarify the effect of lactic acid bacteria
      on the physiological changes with increasing age, heat-killed Lactococcus lactis
      G50 was administered to 1-month-old senescence-accelerated-prone mouse (SAMP)6
      mice for 11 months, a senescence-accelerated mouse strain that develops senile
      osteoporosis. Mice fed G50 gained more weight than the control mice (not fed G50)
      during the feeding experiment. Faecal IgA levels in the mice fed G50 at 3 months
      were higher than those of the control mice but decreased to control levels with
      increasing age. The numbers of viable cells of Bacteroides sp., Lactobacillus
      sp., Staphylococcus sp., Enterococcus/Streptococcus sp. and Enterobacteriaceae
      sp. in faeces were similar for mice fed the G50 and control diets at any age, but
      strain G50 suppressed the intestinal growth of H2S-producing bacteria. Bone
      density of the thigh bone did not differ between aged G50 and control mice.
      Strain G50 would be a beneficial bacterium for the enhancement of intestinal
      immunity during youth and to suppress the growth of harmful intestinal bacteria.
      The applicability of strain G50 for the food and animal industries has been
      proposed in the present study.

PMID- 19586566
TI  - Changes between 1982 and 2000 in the prevalence of behavioral symptoms and
      psychotropic drug treatment among old people with cognitive impairment in
      geriatric care.
AB  - BACKGROUND: People with a dementia disorder often live in institutional care
      facilities, particularly when the dementia disorder becomes severe or complicated
      by various behavioral disturbances. The aim of the present study was to analyze
      and compare the one-week prevalence of various behavioral symptoms and
      psychotropic drug treatment among people with cognitive impairment living in
      institutional care, in two large, comparable samples from 1982 and 2000. METHODS:
      A comparison was made between two cross-sectional samples, collected in 1982 and
      2000 respectively, comprising 3404 participants with cognitive impairment living
      in geriatric care units in the county of Vasterbotten, Sweden. Behavioral
      symptoms were measured using the Multi-Dimensional Dementia Assessment Scale
      (MDDAS) and cognition was measured using Gottfries' cognitive scale. RESULTS:
      Eight out of 25 behavioral symptoms had become less common, and six more common,
      after controlling for demographic changes. Regressive behavior, resistance to
      care and passiveness became less common, while certain aberrant motor behaviors
      showed an increased prevalence. Antidepressant drug use increased from 6.8% to
      43.2%, antipsychotic drug use decreased from 38.0% to 26.2% and anxiolytics,
      hypnotic and sedative drug use increased from 12.7% to 38.5%. CONCLUSION: One
      week prevalence of regressive symptoms and resistance to care had decreased and
      there were signs of a generally increased activity level among old people with
      cognitive impairment living in institutional geriatric care in 2000 compared to
      1982. These changes may be an effect of the extensive changes in pharmacological
      treatments and in the organization of institutional geriatric care.

PMID- 19586568
TI  - A 12-week lutein supplementation improves visual function in Chinese people with
      long-term computer display light exposure.
AB  - We aimed to examine the effect of different doses of lutein supplementation on
      visual function in subjects with long-term computer display light exposure.
      Thirty-seven healthy subjects with long-term computer display light exposure
      ranging in age from 22 to 30 years were randomly assigned to one of three groups:
      Group L6 (6 mg lutein/d, n 12); Group L12 (12 mg lutein/d, n 13); and Group
      Placebo (maltodextrin placebo, n 12). Levels of serum lutein and visual
      performance indices such as visual acuity, contrast sensitivity and glare
      sensitivity were measured at weeks 0 and 12. After 12-week lutein
      supplementation, serum lutein concentrations of Groups L6 and L12 increased from
      0.356 (SD 0.117) to 0.607 (SD 0.176) micromol/l, and from 0.328 (SD 0.120) to
      0.733 (SD 0.354) micromol/l, respectively. No statistical changes from baseline
      were observed in uncorrected visual acuity and best-spectacle corrected visual
      acuity, whereas there was a trend toward increase in visual acuity in Group L12.
      Contrast sensitivity in Groups L6 and L12 increased with supplementation, and
      statistical significance was reached at most visual angles of Group L12. No
      significant change was observed in glare sensitivity over time. Visual function
      in healthy subjects who received the lutein supplement improved, especially in
      contrast sensitivity, suggesting that a higher intake of lutein may have
      beneficial effects on the visual performance.

PMID- 19586569
TI  - Clinical severity scores do not predict tolerance to enteral nutrition in
      critically ill children.
AB  - The objective of the present study was to analyse whether there is a relationship
      between the clinical severity at the time of starting transpyloric enteral
      nutrition (TEN) and the onset of digestive tract complications in critically ill
      children. Between May 2005 and December 2007, we performed a prospective,
      observational study with the participation of 209 critically ill children aged
      between 3 d and 17 years and who received TEN. The characteristics of the
      nutrition and its tolerance were compared with the paediatric risk of mortality
      (PRISM), the paediatric index of mortality (PIM) and the paediatric logistic
      organ dysfunction index (PELOD) at the time of starting the nutrition. Higher
      PRISM and PELOD scores correlated with a later time of starting enteral
      nutrition, a longer time to reach the maximum daily energy delivery and a longer
      duration of the TEN. However, the severity scores did not correlate with the
      maximum energy delivery achieved. Abdominal distension or excessive gastric
      residues were observed in 4.7 % of the patients and diarrhoea in 4.3 %. The
      ability of the severity scores to predict diarrhoea was of 0.67 for PRISM, 0.63
      for PELOD and 0.60 for PIM-2.The severity scores were not able to predict other
      digestive tract complications. Higher scores of clinical severity at the time of
      starting enteral nutrition correlate with a later initiation of the nutrition, a
      longer time to reach the maximum energy delivery and a longer duration of TEN.
      However, their ability to predict digestive tract complications is low.

PMID- 19586570
TI  - Impact of a lignan-rich diet on adiposity and insulin sensitivity in post
      menopausal women.
AB  - There has been a growing interest in lignans, a class of phyto-oestrogens,
      because of their potentially favourable effects on human health. The aim of the
      present study was to compare the metabolic profile of post-menopausal women
      consuming various amounts of dietary lignans. Phyto-oestrogen intake was assessed
      using a 3-d dietary record analysed with a Canadian food phyto-oestrogen content
      data table in 115 post-menopausal women (age 56.8 (SD 4.4) years and BMI 28.5 (SD
      5.9) kg/m(2)). Plasma enterolactone (ENL), the major biologically active
      metabolite of dietary lignans, was determined by time-resolved fluoroimmunoassay.
      Anthropometrics, abdominal adipose tissue areas (computed tomography), body
      composition (hydrostatic weighing) and insulin sensitivity (hyperinsulinaemic
      euglycaemic clamp) were measured in all women. Women in the high dietary lignan
      intake subgroup (n 29) had a significantly lower BMI and total body fat mass, as
      well as a better glucose disposal rate (GDR; P < 0.05), compared with women in
      the low lignan intake subgroup (n 28). The majority of women with the highest
      dietary lignan intake were also in the highest quartile of plasma ENL (59 %).
      Women in the highest ENL quartile had a significantly lower BMI (26.1 (SD 4.4) v.
      30.4 (SD 6.9) kg/m(2), P < 0.05), total body fat mass (24.8 (SD 9.8) v. 33.3 (SD
      13.3) kg, P < 0.05), 2 h postload glycaemia (5.5 (SD 0.9) v. 5.7 (sd 0.8) nmol/l,
      P < 0.05) and a higher GDR (8.3 (SD 2.7) v. 5.5 (SD 2.8), P < 0.01) compared with
      women in the lowest ENL quartile. In conclusion, women with the highest ENL
      concentrations had a better metabolic profile including higher insulin
      sensitivity and lower adiposity measures.

PMID- 19586571
TI  - Dihydroxylated phenolic acids derived from microbial metabolism reduce
      lipopolysaccharide-stimulated cytokine secretion by human peripheral blood
      mononuclear cells.
AB  - Oligomers and polymers of flavan-3-ols (proanthocyanidins) are very abundant in
      the Mediterranean diet, but are poorly absorbed. However, when these polyphenols
      reach the colon, they are metabolised by the intestinal microbiota into various
      phenolic acids, including phenylpropionic, phenylacetic and benzoic acid
      derivatives. Since the biological properties of these metabolites are not
      completely known, in the present study, we investigated the effect of the
      following microbial phenolic metabolites: 3,4-dihydroxyphenylpropionic acid (3,4
      DHPPA), 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid (3,4
      DHPAA), 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid and 4-hydroxyhippuric
      acid (4-HHA), on modulation of the production of the main pro-inflammatory
      cytokines (TNF-alpha, IL-1beta and IL-6). The production of these cytokines by
      lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) pre
      treated with the phenolic metabolites was studied in six healthy volunteers. With
      the exception of 4-HHA for TNF-alpha secretion, only the dihydroxylated
      compounds, 3,4-DHPPA and 3,4-DHPAA, significantly inhibited the secretion of
      these pro-inflammatory cytokines in LPS-stimulated PBMC. Mean inhibition of the
      secretion of TNF-alpha by 3,4-DHPPA and 3,4-DHPAA was 84.9 and 86.4 %,
      respectively. The concentrations of IL-6 in the culture supernatant were reduced
      by 88.8 and 92.3 % with 3,4-DHPPA and 3,4-DHPAA pre-treatment, respectively.
      Finally, inhibition was slightly higher for IL-1beta, 93.1 % by 3,4-DHPPA and
      97.9 % by 3,4-DHPAA. These results indicate that dihydroxylated phenolic acids
      derived from microbial metabolism present marked anti-inflammatory properties,
      providing additional information about the health benefits of dietary polyphenols
      and their potential value as therapeutic agents.

PMID- 19586572
TI  - d- chiro-Inositol is absorbed but not synthesised in rodents.
AB  - d-chiro-inositol (DCI) and pinitol (1d-3-O-methyl-chiro-inositol) are distinctive
      inositols reported to possess insulin-mimetic properties. DCI-containing
      compounds are abundant in common laboratory animal feed. By GC-MS of 6 m-HCl
      hydrolysates, Purina Laboratory Rodent Diet 5001 (diet 5001) contained 0.23 %
      total DCI by weight with most found in the lucerne and soya meal components. In
      contrast, only traces of l-chiro-inositol were observed. The DCI moiety was
      present in a water-soluble non-ionic form of which most was shown to be pinitol.
      To measure the absorption of dietary inositols, rats were fed diet 5001 in a
      balance study or given purified pinitol or [2H6]DCI. More than 98 % of the total
      DCI fed to rats as diet 5001, purified pinitol or [2H6]DCI was absorbed from the
      gastrointestinal tract. Rats chronically on diet 5001 consumed 921 mumol total
      DCI/kg body weight per d but excreted less than 5.3 % in the stools and urine,
      suggesting that the bulk was metabolised. The levels of pinitol or DCI in plasma,
      stools or urine remained relatively stable in mice fed Purina PicoLab Rodent Diet
      20 5053 over a 5-week period, whereas these values declined to very low levels in
      mice fed a pinitol/DCI-deficient chemically defined diet. To test whether DCI was
      synthesised or converted from myo-inositol, mice were treated with heavy water or
      [2H6]myo-inositol. DCI was neither synthesised endogenously from 2H-labelled
      water nor converted from [2H6]myo-inositol. DCI and pinitol in rodents appear to
      be derived solely from the diet.

PMID- 19586573
TI  - Dietary carbohydrates, glycaemic load, food groups and newly detected type 2
      diabetes among urban Asian Indian population in Chennai, India (Chennai Urban
      Rural Epidemiology Study 59).
AB  - The aim of the study was to examine the association of dietary carbohydrates and
      glycaemic load with the risk of type 2 diabetes among an urban adult Asian Indian
      population. Adult subjects aged >20 years (n 1843) were randomly selected from
      the Chennai Urban Rural Epidemiology Study, in Chennai city in southern India.
      Dietary carbohydrates, glycaemic load and food groups were assessed using FFQ.
      Oral glucose tolerance tests were performed using 75 g glucose in all subjects.
      Diagnosis of diabetes was based on WHO Consulting Group criteria. OR for newly
      detected diabetes were calculated for carbohydrates, glycaemic load and specific
      food groups comparing subjects in the highest with those in the lowest quartiles,
      after adjustment for potential confounders such as age, sex, BMI, family history
      of diabetes, physical activity, current smoking, alcohol consumption and relevant
      dietary factors. We identified 156 (8.5 %) newly diagnosed cases of type 2
      diabetes. Refined grain intake was positively associated with the risk of type 2
      diabetes (OR 5.31 (95 % CI 2.98, 9.45); P < 0.001). In the multivariate model,
      after adjustment for potential confounders, total carbohydrate (OR 4.98 (95 % CI
      2.69, 9.19), P < 0.001), glycaemic load (OR 4.25 (95 % CI 2.33, 7.77); P < 0.001)
      and glycaemic index (OR 2.51 (95 % CI 1.42, 4.43); P = 0.006) were associated
      with type 2 diabetes. Dietary fibre intake was inversely associated with diabetes
      (OR 0.31 (95 % CI 0.15, 0.62); P < 0.001). In urban south Indians, total dietary
      carbohydrate and glycaemic load are associated with increased, and dietary fibre
      with decreased, risk of type 2 diabetes.

PMID- 19586574
TI  - In vivo metabolic tracking of 14C-radiolabelled isoflavones in kudzu (Pueraria
      lobata) and red clover (Trifolium pratense) extracts.
AB  - Absorption, distribution and elimination of 14C-labelled isoflavone-containing
      extracts from kudzu (Pueraria lobata) root culture and red clover (Trifolium
      pratense) cell culture were investigated in an in vivo rat model. The predominant
      isoflavones in the kudzu extract were the glycosides puerarin, daidzin and
      malonyl daidzin, while in the red clover extract, the major isoflavones were
      formononetin and its derivatives, genistein and biochanin A, with radioactivities
      of 3.770 and 7.256 MBq/g, respectively. Male Sprague-Dawley rats, implanted with
      a jugular catheter and a subcutaneous ultrafiltrate probe, were orally
      administered with 14C-labelled isoflavone extracts from either kudzu or clover
      cell cultures. Serum, interstitial fluid (ISF), urine and faeces were collected
      using a Culex Automated Blood Collection System for 24 h. Analysis of bone
      tissues revealed that radiolabel accumulated in the femur, tibia and vertebrae at
      0.04, 0.03 and 0.01 % of the administered dose, respectively, in both kudzu and
      red clover treatments. The liver accumulated the greatest concentration of
      radiolabel among the tissues tested, at 1.99 and 1.54 % of the administered kudzu
      and red clover extracts, respectively. Serum and ISF analysis showed that both
      extracts were rapidly absorbed, distributed in various tissues, and largely
      eliminated in the urine and faeces. Urine and faeces contained 8.53 and 9.06 % of
      the kudzu dose, respectively, and 3.60 and 5.64 % of the red clover dose,
      respectively. Serum pharmacokinetics suggest that extracts from kudzu may undergo
      enterohepatic circulation.

PMID- 19586575
TI  - Measurements of adiposity and high blood pressure among children and adolescents
      living in Belo Horizonte.
AB  - OBJECTIVE: To verify an association, if it exists, between obesity and blood
      pressure raised beyond the 90th percentile in children and adolescents, and to
      determine the measure of adiposity that best correlates with blood pressure in
      these subjects. DESIGN: Cross-sectional study. SETTING: A school-based study in
      Belo Horizonte, Brazil. PARTICIPANTS: We selected randomly 1,403 students, aged
      from 6 to 18 years, from 545,046 students attending 521 public and private
      schools. Those selected completed the study. MAIN MEASURES OF OUTCOME: We
      recorded the weight, height, skin fold in the triceps, subscapular, and
      suprailiac areas, waist and hip circumference, body-mass index, and resting
      systolic and diastolic blood pressures using a mercury sphygmomanometer. RESULTS:
      In univariate analyses, body mass index greater or lesser than 85th percentile,
      measurements of skin thickness in the subscapular and suprailiac areas, and the
      sum of all measurements of skinfold thickness, were associated with both systolic
      and diastolic measurements of blood pressure. After multivariate analyses that
      adjusted for all measurements of adiposity except itself, and age, race, and
      socioeconomic state, we found that the increased body mass index was associated
      with a 3.6-fold increased frequency of elevated systolic measurements of blood
      pressure, with 95% confidence intervals from 2.2 to 5.8, and a 2.7-fold increased
      frequency of elevated measurements of diastolic blood pressure, with 95%
      confidence intervals from 1.9 to 4.0. CONCLUSIONS: Body-mass index serves as a
      better predictor of elevated blood pressure among children than do local
      measurements of adiposity.

PMID- 19586577
TI  - Pheromone communication channels in tortricid moths: lower specificity of alcohol
      vs. acetate geometric isomer blends.
AB  - Discrimination of conspecific and heterospecific signals is a key element in the
      evolution of specific mate recognition systems. Lepidopteran pheromone signals
      are typically composed of several compounds that synergize attraction of
      conspecific and inhibit attraction of heterospecific males. Blends convey
      specificity, but not their single components, that are typically shared by
      several species. Many sex pheromones are blends of geometric or positional
      isomers of straight-chain acetates, while species-specific blends of analogous
      alcohols have not been described. We have, therefore, studied the attraction of
      tortricid moths to the geometric isomers (E,E)-, (E,Z)-, (Z,E)- and (Z,Z)-8,10
      dodecadien-1-ol. Only one species responding to these alcohols seemed to be
      attracted to a blend of two isomers, while most species are attracted to only one
      alcohol isomer. Lack of a pronounced synergist or antagonist effect of the other
      geometric isomers explains the lack of specific attraction to isomer blends and
      reduces accordingly the number of specific communication signals composed of
      these alcohols. In comparison, many more species respond to the analogous (E,E)-,
      (E,Z)-, (Z,E)- and (Z,Z)-8,10-dodecadienyl acetates and their binary blends. The
      acetate isomers all play a behavioural role, either as attractants, attraction
      synergists or antagonists, and thus promote specific communication with acetate
      blends. Male moths seem to discriminate the acetate isomers with greater
      precision than the analogous alcohols. It is proposed that discrimination is
      facilitated by steric differences between the four acetate isomers, as compared
      to the more uniform steric properties of the alcohols.

PMID- 19586576
TI  - Field-scale dispersal of Aphodius dung beetles (Coleoptera: Scarabaeidae) in
      response to avermectin treatments on pastured cattle.
AB  - Very few studies have examined, at the field scale, the potential for faecal
      residues in the dung of avermectin-treated cattle to affect dung-breeding
      insects. The current study examined populations of dung beetles (Scarabaeidae:
      Aphodius) using pitfall traps baited with dung from untreated cattle on 26 fields
      across eight farms in southwest Scotland. The fields were grazed either by
      untreated cattle or by cattle treated with an avermectin product, i.e. doramectin
      or ivermectin. During the two-year study, significantly more beetles were trapped
      in fields grazed by treated cattle (n=9377 beetles) than in fields where cattle
      remained untreated (n=2483 beetles). Additional trials showed that beetles
      preferentially colonised dung of untreated versus doramectin-treated cattle. This
      may explain the higher captures of beetles in traps baited with dung of untreated
      cattle, which were located in fields of treated cattle. Given that Aphodius
      beetles avoided dung of treated cattle in the current study, the potential
      harmful effects of avermectin residues in cattle dung could be reduced through
      livestock management practices that maximise the availability of dung from
      untreated livestock in areas where avermectins are being used.

PMID- 19586578
TI  - The failure to discriminate: superparasitism of Trichoplusia ni Hubner by a
      generalist tachinid parasitoid.
AB  - Parasitoids are dependent on their hosts, which provide all of the resources for
      larval development. Parasitoid fitness, therefore, is directly related to the
      host quality, as determined by host size, age and health (e.g. parasitisation
      status); and this can only be assessed by the female parasitoid during host
      selection. Most studies of parasitoid-host interactions have focused on
      hymenopteran parasitoids rather than dipterans that are believed to be less
      discriminating during host selection. We assessed the impact of host quality and
      superparasitism on parasitoid fitness in Compsilura concinnata Meigen, a
      gregarious tachinid dipteran parasitoid, and its lepidopteran host the cabbage
      looper, Trichoplusia ni Hubner. Female C. concinnata parasitised all host stages
      of T. ni that were presented to them, but emergence rates were higher from older
      hosts. Females readily superparasitised hosts. The number of flies emerging was
      higher from hosts parasitised at later instars, and flies emerged earlier from
      heavily superparasitised hosts. Superparasitism decreased parasitoid pupal weight
      and development time, indicating intra-host competition between parasitoid larvae
      and skewed the parasitoid sex ratio in favour of males. Host discrimination does
      not seem to be well developed in C. concinnata. Hosts are superparasitised
      despite the effects of superparasitism on offspring and sex ratio. This could be
      due to the wide host range of C. concinnata; avoiding high superparasitism could
      occur naturally due to host switching and, therefore, developing host
      discrimination mechanisms for one host species may not be crucial.

PMID- 19586579
TI  - Assessment of clinical improvement and quality of life before and after
      tonsillectomy.

PMID- 19586580
TI  - Lateral soft tissue neck X-rays: are they useful in management of upper aero
      digestive tract foreign bodies?

PMID- 19586581
TI  - Prognostic scoring in necrotising otitis externa.
AB  - OBJECTIVE: To collect and analyse data from the published literature concerning
      the rare condition necrotising otitis externa, in order to formulate a prognostic
      scoring model based on signs and symptoms. DESIGN: Retrospective data collection
      from published literature, and binary logistic regression analysis of the effect
      on outcome of identified signs and symptoms. RESULTS: Six factors were identified
      as prognostic of a poorer outcome, including facial nerve involvement, additional
      cranial nerve involvement, non-cranial nerve neurological involvement, extensive
      granulations (or oedema) in the external auditory canal, bilateral symptoms and
      aspergillus species as the causative organism. A four-point scoring model based
      on these findings is presented. CONCLUSIONS: A novel, systematic method of data
      analysis was utilised to construct a prognostic scoring model for necrotising
      otitis externa. This will better equip clinicians to treat this potentially fatal
      condition.

PMID- 19586582
TI  - An unusual middle-ear mass.
AB  - OBJECTIVE: We describe a case of endolymphatic sac tumour confined to the middle
      ear, which radiologically mimicked a glomus tympanicum, in a 58-year-old woman
      with tinnitus. CASE REPORT: A 58-year-old woman presented with a one-year history
      of right-sided tinnitus. The clinical, radiological and surgical features were
      felt to be in keeping with a glomus tympanicum. However, the histopathological
      picture was that of a low grade papillary carcinoma of the endolymphatic sac,
      i.e. an endolymphatic sac tumour. CONCLUSION: Endolymphatic sac tumours are
      classically locally aggressive and centred around the petrous temporal bone.
      Further growth results in complete replacement of the mastoid and petrous pyramid
      by tumour. To the best of our knowledge, there have been no previous reports of
      an endolymphatic sac tumour located solely within the hypo- and epitympanum of
      the middle ear.

PMID- 19586583
TI  - What is the best way to change self-efficacy to promote lifestyle and
      recreational physical activity? A systematic review with meta-analysis.
AB  - PURPOSE: Increasing self-efficacy is an effective method to increase physical
      activity. Despite this, the evidence concerning the most effective techniques to
      increase self-efficacy in physical activity interventions has not been
      systematically reviewed. The aim of the present research is to systematically
      gather, and meta-analyse, intervention studies which aimed to increase self
      efficacy for physical activity; to estimate the association between intervention
      techniques used, and change in self-efficacy achieved. METHODS: A systematic
      database search was conducted for papers reporting lifestyle or recreational
      physical activity interventions. Published intervention studies explicitly
      targeting self-efficacy in order to change physical activity behaviour in
      'healthy' adults were eligible for inclusion. RESULTS: The search strategy
      identified 27 unique physical activity intervention studies, with a total of
      5,501 participants. A significant, yet small, relationship between the
      interventions and changes in self-efficacy was found (mean d=0.16, p<.001). Owing
      to significant heterogeneity, moderator analyses were conducted, examining the
      association of changes in self-efficacy with whether or not specific intervention
      techniques were used. Interventions that included feedback on past or others'
      performance produced the highest levels of self-efficacy found in this review.
      Vicarious experience was also associated with higher levels of self-efficacy.
      Persuasion, graded mastery, and barrier identification were associated with lower
      levels of self-efficacy. CONCLUSIONS: This meta-analysis forms an evidence base
      for which psychological techniques are most effective in increasing self-efficacy
      for physical activity. The results are presented in terms of recommendations for
      those developing interventions and directions for future research.

PMID- 19586584
TI  - Systematic review and individual patient data meta-analysis of diagnosis of heart
      failure, with modelling of implications of different diagnostic strategies in
      primary care.
AB  - OBJECTIVES: To assess the accuracy in diagnosing heart failure of clinical
      features and potential primary care investigations, and to perform a decision
      analysis to test the impact of plausible diagnostic strategies on costs and
      diagnostic yield in the UK health-care setting. DATA SOURCES: MEDLINE and CINAHL
      were searched from inception to 7 July 2006. 'Grey literature' databases and
      conference proceedings were searched and authors of relevant studies contacted
      for data that could not be extracted from the published papers. REVIEW METHODS: A
      systematic review of the clinical evidence was carried out according to standard
      methods. Individual patient data (IPD) analysis was performed on nine studies,
      and a logistic regression model to predict heart failure was developed on one of
      the data sets and validated on the other data sets. Cost-effectiveness modelling
      was based on a decision tree that compared different plausible investigation
      strategies. RESULTS: Dyspnoea was the only symptom or sign with high sensitivity
      (89%), but it had poor specificity (51%). Clinical features with relatively high
      specificity included history of myocardial infarction (89%), orthopnoea (89%),
      oedema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), added
      heart sounds (99%), lung crepitations (81%) and hepatomegaly (97%). However, the
      sensitivity of these features was low, ranging from 11% (added heart sounds) to
      53% (oedema). Electrocardiography (ECG), B-type natriuretic peptides (BNP) and N
      terminal pro-B-type natriuretic peptides (NT-proBNP) all had high sensitivities
      (89%, 93% and 93% respectively). Chest X-ray was moderately specific (76-83%) but
      insensitive (67-68%). BNP was more accurate than ECG, with a relative diagnostic
      odds ratio of ECG/BNP of 0.32 (95% CI 0.12-0.87). There was no difference between
      the diagnostic accuracy of BNP and NT-proBNP. A model based upon simple clinical
      features and BNP derived from one data set was found to have good validity when
      applied to other data sets. A model substituting ECG for BNP was less predictive.
      From this a simple clinical rule was developed: in a patient presenting with
      symptoms such as breathlessness in whom heart failure is suspected, refer
      directly to echocardiography if the patient has a history of myocardial
      infarction or basal crepitations or is a male with ankle oedema; otherwise, carry
      out a BNP test and refer for echocardiography depending on the results of the
      test. On the basis of the cost-effectiveness analysis carried out, such a
      decision rule is likely to be considered cost-effective to the NHS in terms of
      cost per additional case detected. The cost-effectiveness analysis further
      suggested that, if likely benefit to the patient in terms of improved life
      expectancy is taken into account, the optimum strategy would be to refer all
      patients with symptoms suggestive of heart failure directly for echocardiography.
      CONCLUSIONS: The analysis suggests the need for important changes to the NICE
      recommendations. First, BNP (or NT-proBNP) should be recommended over ECG and,
      second, some patients should be referred straight for echocardiography without
      undergoing any preliminary investigation. Future work should include evaluation
      of the clinical rule described above in clinical practice.

PMID- 19586586
TI  - Percutaneous CT-guided C1-2 cordotomy for intractable cancer pain.

PMID- 19586585
TI  - The role of botulinum neurotoxin in pain management--an ongoing controversy.

PMID- 19586587
TI  - Diagnostic evaluation and treatment of trigeminal neuralgia.

PMID- 19586588
TI  - Medical imaging in the diagnosis and management of cancer pain.
AB  - Within the past few decades medical imaging has evolved very rapidly, now
      becoming an indispensable tool for the diagnosis, treatment, and follow-up of
      patients with cancer-related pain. Multiple imaging modalities are available for
      the assessment of cancer patients, each one with different advantages and
      limitations that are important to consider at the time we order a diagnostic
      study or plan an image-guided procedure. This article reviews the role that
      various imaging modalities play in the management of cancer pain and provides an
      overview of the latest technological advances.

PMID- 19586590
TI  - Stereotactic radiosurgery in the management of cancer pain.
AB  - Pain can be a significant problem for the patient with advanced cancer,
      particularly if bone metastases are present. Radiation therapy is efficacious and
      has been a mainstay in the treatment of pain from bone metastases. In the past
      decade, radiosurgery has developed into a successful adjunct treatment for these
      patients. The indications for radiosurgery are continually expanding, and new and
      more sophisticated equipment is being developed to deliver more precise
      treatments. This article discusses the biology, rationale, evolution, and future
      direction of radiosurgery for the treatment of pain related to bony metastatic
      disease.

PMID- 19586589
TI  - Radiation, chemotherapy, and symptom management in cancer-related cognitive
      dysfunction.
AB  - Patients with cancer are concerned about their ability to interact with friends
      and family and to perform activities associated with daily living. The combined
      effects of the disease process, its treatment with surgery, radiation, and
      chemotherapy, and the medications used to manage symptoms may all impact
      cognitive function. Minimizing the effect of each treatment modality on cognitive
      processing requires an understanding of how these treatment modalities may impact
      cognition.

PMID- 19586591
TI  - Assessment of neuropathic pain in cancer patients.
AB  - Neuropathic pain is an increasingly common problem facing the cancer patient.
      Painful neuropathy can come from various sources and significantly impact quality
      of life. The most commonly observed scenario is paraesthesia and dysesthesia as a
      result of toxic effects of chemotherapies on the distal peripheral nerves.
      Neuropathic pain should be addressed ideally with the help of a neuro-oncologist,
      and it usually can be successfully treated with a variety of agents, including
      atypical analgesics such as antidepressants, newer drugs with analgesic benefit,
      and opioids for more refractory cases. Direct and indirect effects of the primary
      neoplasm need to be considered in the etiology of specific syndromes of
      mononeuropathies and plexopathies.

PMID- 19586592
TI  - Vertebroplasty in the management of painful bony metastases.
AB  - Percutaneous vertebroplasty is the injection of bone cement, usually
      polymethylmethacrylate into the vertebral body. This procedure is most often
      performed in a percutaneous fashion on an outpatient (or short-stay) basis. Among
      other indications, the procedure is designated for painful vertebral compression
      fractures due to primary or metastatic spinal tumors. Published literature favors
      the use of this procedure in cancer pain management. The overall risk of the
      procedure is low, although serious complications (including spinal cord
      compression) can occur. Recent advances in technique and materials may reduce the
      incidence of adverse outcomes. Proper patient selection and meticulous technique
      are required to achieve best results and to avoid complications.

PMID- 19586593
TI  - The management of sickle cell pain.
AB  - Treatment of pain in the setting of sickle cell disease remains unsatisfactory.
      The approach remains to treat the pain symptomatically with escalating doses of
      non-opioid and opioid medications while any underlying inciting process is
      investigated. For the majority of patients with sickle cell disease, pain will
      always be part of their lives. Advances in the treatment of sickle cell pain will
      depend on multiple approaches, including both pharmacologic and nonpharmacologic.

PMID- 19586594
TI  - Overuse of acute migraine medications and migraine chronification.
AB  - Among individuals with episodic migraine, the influence of excessive acute
      medication use on the development of chronic migraine depends upon within-person
      characteristics (eg, headache frequency), class of drug, and frequency of
      medication use. Available data suggest that opioids induce migraine
      chronification (progression), and the effect is dose dependent (critical dose
      around 8 days of exposure per month) and more pronounced in men. Barbiturates
      also induce migraine progression, and the effect is dose dependent (critical dose
      around 5 days of exposure per month) and more pronounced in women. Triptans
      induce migraine progression only in those with high migraine frequency at
      baseline (10-14 days per month), but not overall. NSAIDs protect against migraine
      progression unless individuals have 10 or more headache days per month (when they
      become inducers, rather than protective). Finally, caffeine-containing over-the
      counter products increase risk of progression. While we await randomized trials,
      these findings should inform the choice of acute migraine treatments with the
      goal of reducing the risk of migraine progression to chronic migraine.

PMID- 19586596
TI  - Temporomandibular disorders and migraine chronification.
AB  - Among the established and potential comorbidities of migraine, the
      temporomandibular disorders (TMD) are rarely discussed, although they are of
      importance for several reasons. TMD may cause headaches per se, worsen existent
      primary headaches, and add to the burden of headache disorders. This article
      explores the potential comorbidity between migraine and TMD and the role of TMD
      as a potential factor to induce chronic migraine. We discuss the similarities
      between both conditions, review evidence to support the idea that both disorders
      are comorbid, and highlight the limited evidence suggesting that TMD influence
      migraine progression. Finally, we discuss the importance of cutaneous allodynia
      mediating the TMD/frequent headache relationship.

PMID- 19586595
TI  - Chronic pain disorders and headache chronification.
AB  - It is estimated that nearly half of the global adult population suffers from an
      active headache disorder, most of whom experience attacks on an episodic basis.
      The transition from episodic to chronic headache is a poorly understood process.
      Epidemiological findings demonstrating comorbidity and common risk factors
      suggest that headache progression or prognosis may be related to the presence of
      other chronic pain disorders. This review highlights findings from population
      based studies on headache and other pain disorders and how they relate to each
      other, with a focus on understanding headache chronification. We also consider
      the limitations and methodological challenges in understanding how two different
      chronic pain disorders may be related.

PMID- 19586597
TI  - Sinus problems as a cause of headache refractoriness and migraine chronification.
AB  - Sinus headache is not a diagnostic term supported by the academia, yet it appears
      to be understood by the general public and larger medical community. It can be
      considered both a primary and secondary headache disorder. As a primary headache
      disorder, most of the patients considered to have sinus headache indeed have
      migraine (migraine with sinus symptoms). Yet it is also possible that some
      attacks of sinus headache may represent a unique clinical phenotype of migraine
      or be a unique clinical entity. Potentially, primary sinus headache can chronify
      and be refractory through immune-mediated mechanisms or as a catalyst for
      migraine chronification through ineffective treatment or medication overuse and
      misuse. As a secondary headache disorder, sinus headache can be associated with a
      wide range of underlying etiologies such as infection, anatomical abnormalities,
      trauma, and immunological disease or sleep disorders. It is possible that these
      underlying pathophysiological processes generate long-standing activation of
      nociceptive mechanisms involved in headache and can lead to chronification and
      refractoriness of the headache symptomatology. This article explores some of the
      potential mechanisms and the available scientific studies that may explain how
      sinus headache can become chronic and present to the clinician as a refractory
      headache disorder.

PMID- 19586599
TI  - In vivo skin analysis (INSA) for quantitative determination of lotion transfer to
      human skin.
AB  - There is a need during the development of cosmetic and skin products for simple,
      quantitative, noninvasive measurements of product deposition onto skin. In this
      article we describe INSA (in vivo skin analysis) as such a method for measuring
      the amount of lotion transferred to the skin from tissue products. Using Fourier
      transform infrared spectroscopy with an attenuated total reflectance (ATR FT-IR)
      sampling accessory, we were able to quantify lotion levels on the arms of
      subjects in minutes.

PMID- 19586598
TI  - Psychiatric comorbidities and migraine chronification.
AB  - A growing body of literature has implicated comorbid psychopathology as a
      potential risk factor for the chronification of migraine. Of the psychiatric
      disorders, depressive and anxiety disorders have been most consistently
      associated with the chronification of migraine. A shared dysfunction of the
      serotonergic system, medication overuse, and psychological factors have been
      proposed to mediate this relationship, although the responsible mechanisms are
      still largely unclear. This article overviews literature on psychiatric
      comorbidities and migraine chronification, considers mechanisms underlying this
      relationship, and notes directions for future clinical and empirical work.

PMID- 19586600
TI  - Novel mechanism for hair shine with special optical enhancement effect on blonde
      hair.
AB  - Compared with dark or brunette hair, blonde hair has different characteristic
      features of appearance such as bright shine with a soft tonal color. In this
      report, novel optical mechanisms of the characteristic blonde hair appearance are
      reported. Optical analyses of goniophotometric measurements were carried out to
      elucidate the mechanisms of strong reflections observed in blonde hairs. As a
      result, reflections with much higher intensity than those from the front surface
      of a fiber were confirmed to play important roles in the case of blonde hair
      fibers, and the intensities were found to vary with the cross-sectional shape of
      a fiber, the ellipticity (= minor axis/major axis). From light path simulation
      analyses, these strong reflections were verified to result from total reflection
      from the back surface of a fiber. Furthermore, since each hair fiber acts as a
      lens and/or a reflector, intricate reflection behaviors are suggested to occur as
      a consequence of the combination of light condensation and total reflection.

PMID- 19586601
TI  - Copper and calcium uptake in colored hair.
AB  - During hair coloring a number of disulfide bonds in cystine are oxidized (1) to
      create cysteic acid, forming binding sites for metal ions such as Ca(2+ )and
      Cu(2+ )from tap water (2). The increased uptake of these metals can have a
      detrimental impact on fiber properties-for example, reducing shine and causing a
      poor wet and dry feel (3). In addition, the increased uptake of copper can also
      contribute to further fiber damage during subsequent coloring due to its ability
      to take part in metal-induced radical chemistry (4). It is important to know
      where in the fibers these metals are located in order to either effectively
      remove these metals or control their chemistry. Nanoscale secondary ion mass
      spectrometry (NanoSIMS) has been used to locate the calcium and copper within
      hair that has been treated with a colorant and washed multiple times in tap water
      containing these ions. Untreated hair is used as a baseline standard material.
      Images with up to 50-nm spatial resolution of the preferential locations of
      calcium uptake were obtained, showing a high concentration of calcium in the
      cuticle region of colored hair, specifically in the sulfur-rich regions (A-layer
      and exocuticle).

PMID- 19586602
TI  - Tyrosinase inhibitors isolated from the roots of Paeonia suffruticosa.
AB  - The inhibition of mushroom tyrosinase by Paeonia suffruticosa root-derived
      materials was evaluated. Six tyrosinase inhibitors were isolated by ethanol
      extraction, n-hexane, ethyl acetate, n-BuOH, and water partition, silica gel
      column chromatography, Sephadex LH-20, Lobar PR-8, and high-performance liquid
      chromatography methods, and they were identified as kaempferol (I), quercetin
      (II), mudanpioside B (III), benzoyloxypaeoniflorin (IV), mudanpioside H (V), and
      pentagalloyl-beta-(D)-glucose (VI) on the basis of spectroscopic evidence. The
      inhibitory activities of compounds I to VI against mushroom tyrosinase were
      determined with IC(50) values of 0.120, 0.108, 0.368, 0.453, 0.324, and 0.063 mM,
      respectively. The kinetic study indicated that all purified inhibitors acted
      competitively for the L-dopa binding site of the enzyme, with an exception of
      compound VI, which acted non-competitively.

PMID- 19586603
TI  - 8-Hydroxydaidzein is unstable in alkaline solutions.
AB  - 8-Hydroxydaidzein is a suicide substrate of mushroom tyrosinase with potent
      irreversible inhibitory activity. Despite its high potential in the cosmetics
      industry, it was found that 8-hydroxydaidzein was unstable in a formulated cream.
      In this technical note, the stability of 8-hydroxydaidzein in various solutions
      is investigated. The compound was dissolved in a series of solvents, and the
      residual 8-hydroxydaidzeins in the prepared solutions were sequentially
      determined during storage by HPLC. As a result, the loss in time of 8
      hydroxydaidzein in both pH 6.8 phosphate buffer and DMSO showed typical first
      order kinetics, and the loss rate constant of the compound in pH 6.8 phosphate
      buffer (4.48 x 10(-3) hour(-1)) was 18-fold higher than that in DMSO (2.5 x 10(
      4) hour(-1)). The stabilities of the compound in different buffers with pH values
      ranging from pH 5 to pH 9 were determined in advance. The results showed that the
      compound was completely degraded in one day in the pH 8 and pH 9 buffers. In
      contrast, 8-hydroxydaidzein remained stable above 85% after 20 days' storage in
      the pH 5 and pH 6 buffers. In addition to the residual 8-hydroxydaidzein
      analysis, the residual bioactivities, including tyrosinase inhibitory activity
      and DPPH-radical scavenging activity of the 8-hydroxydaidzein solutions after 20
      days' storage in different pH values, were also determined, and the results
      correlated well with those of the stability experiments. All the results
      demonstrated that 8-hydroxydaidzein is unstable in alkaline solutions. According
      to the data in the present report, it is recommended that 8-hydroxydaidzein be
      formulated in an acid solution for its applications.

PMID- 19586609
TI  - Exendin-4 exerts osteogenic actions in insulin-resistant and type 2 diabetic
      states.
AB  - Poor control of glucose homeostasis accounts for diabetes-related bone loss.
      Incretins - GLP-1 and GIP - have been proposed to affect bone turnover. GLP-1,
      apart from its anti-diabetic and other actions, has shown to exert a bone
      anabolic effect in streptozotocin-induced type 2 diabetic (T2D) and fructose
      induced insulin-resistant (IR) rats. Exendin-4 (Ex-4), a peptide of non-mammalian
      nature, is sharing with GLP-1 part of its structural sequence, and also several
      glucoregulatory effects in mammals in an even more efficient manner. We have
      explored the effect of continuous administration (3 days by osmotic pump) of Ex-4
      or saline (control) on bone turnover factors and bone structure in T2D and IR
      rats, compared to N, and the possible interaction of Ex-4 with the Wnt signalling
      pathway. Blood was taken before and after treatment for plasma measurements;
      tibiae and femurs were collected for gene expression of bone markers (RT-PCR) and
      structure (microCT) analysis; we also measured the mRNA levels of LRP5 - an
      activator of the Wnt pathway - and those of DKK1 and sclerostin (SOST) - both
      blockers of LRP5 activity. Compared to N-control, plasma glucose and insulin were
      respectively higher and lower in T2D; osteocalcin (OC) and tartrate-resistant
      alkaline phosphatase 5b (TRAP5b) were lower; after Ex-4, these turnover markers
      were further reduced in T2D and IR, while TRAP5b increased in N. Bone OC,
      osteoprogeterin (OPG) and receptor activator of NF-kB ligand (RANKL) mRNA were
      lower in T2D and IR; Ex-4 increased OC in all groups and OPG in N and IR, reduced
      RANKL in N and T2D but increased it in IR; the LRP5/DKK1 and LRP5/SOST mRNA
      ratios were similarly decreased in T2D, but in IR, the latter ratio was reduced
      while the former was increased; after Ex-4, both ratios augmented in N, and that
      of LRP5/DKK1 tended to normalize in T2D and IR. In conclusion, Ex-4 exerts
      osteogenic effects in T2D and IR models, and interacts with the Wnt pathway to
      promote bone formation.

PMID- 19586610
TI  - Essential oil of Lindera neesiana fruit: chemical analysis and its potential use
      in topical applications.
AB  - The composition of the essential oil of Lindera neesiana Kurz fruit was examined
      by GC-MS, (1)H, (13)C and bidimensional NMR techniques (HMQC, HMBC, COSY, TOCSY).
      Forty compounds were identified, representing approximately 86% of the oil: Z
      citral (15.08%), E-citral (11.89%), eucalyptol (8.75%), citronellal (6.72%),
      alpha-pinene (6.63%) and beta-pinene (5.61%) were the major components. The
      essential oil of L. neesiana fruit showed significant antimicrobial activity
      against Staphylococcus aureus and Candida albicans at non-cytotoxic doses in
      human keratinocytes, suggesting possible topical applications. GRAPHICAL
      ABSTRACT: The essential oil of Lindera neesiana was investigated by GC-MS and NMR
      techniques. Its biological activities suggest possible topical applications.

PMID- 19586611
TI  - Role of CXCR4/SDF-1 alpha in the migratory phenotype of hepatoma cells that have
      undergone epithelial-mesenchymal transition in response to the transforming
      growth factor-beta.
AB  - Treatment of FaO rat hepatoma cells with TGF-beta selects cells that survive to
      its apoptotic effect and undergo epithelial-mesenchymal transitions (EMT). We
      have established a cell line (T beta T-FaO, from TGF-beta-treated FaO) that shows
      a mesenchymal, de-differentiated, phenotype in the presence of TGF-beta and is
      refractory to its suppressor effects. In the absence of this cytokine, cells
      revert to an epithelial phenotype in 3-4 weeks and recover the response to TGF
      beta. T beta T-FaO show higher capacity to migrate than that observed in the
      parental FaO cells. We found that FaO cells express low levels of CXCR4 and do
      not respond to SDF-1 alpha. However, TGF-beta up-regulates CXCR4, through a NF
      kappaB-dependent mechanism, and T beta T-FaO cells show elevated levels of CXCR4,
      which is located in the presumptive migration front. A specific CXCR4 antagonist
      (AMD3100) attenuates the migratory capacity of T beta T-FaO cells on collagen
      gels. Extracellular SDF-1 alpha activates the ERKs pathway in T beta T-FaO, but
      not in FaO cells, increasing cell scattering and protecting cells from apoptosis
      induced by serum deprivation. Targeted knock-down of CXCR4 with specific siRNA
      blocks the T beta T-FaO response to SDF-1 alpha. Thus, the SDF-1/CXCR4 axis might
      play an important role in mediating cell migration and survival after a TGF-beta
      induced EMT in hepatoma cells.

PMID- 19586612
TI  - Down-regulating protein kinase C alpha: functional cooperation between the
      proteasome and the endocytic system.
AB  - Ubiquitination, proteasome, caveolae and endosomes have been implicated in
      controlling protein kinase C alpha (PKC alpha) down-regulation. However, the
      molecular mechanism remained obscure. Here we show that endosomes and proteasome
      cooperate in phorbol ester 12-O-tetradecanoyl phorbol acetate (TPA)-induced down
      regulation of PKC alpha. We show that following TPA treatment and translocation
      to the plasma membrane, PKC alpha undergoes multimonoubiquitination prior to its
      degradation by the proteasome. However, to reach the proteasome, PKC alpha must
      travel through the endocytic system from early to late endosomes. This route
      requires functional endosomes, whereby endosomal alkalinization, or ablation,
      abrogates completely PKC alpha degradation maintaining the enzyme at the plasma
      membrane. This route also depends on synaptotagmin (Syt) II and the Rab7 GTPase,
      whereby Syt II knock-down or expression of the GDP-locked Rab7 inactive mutant
      prevents PKC alpha degradation. We further show that proteasome plays a dual
      role, where an active proteasome is required for deubiquitination of PKC alpha, a
      step crucial to prevent PKC alpha targeting to the endocytic recycling
      compartment. Finally, we show that the association with rafts-localized cell
      surface proteins that internalize in a clathrin-independent fashion is necessary
      to allow the trafficking of PKC alpha from the plasma membrane to the proteasome,
      its ultimate degradation station.

PMID- 19586613
TI  - p38alpha- and DYRK1A-dependent phosphorylation of caspase-9 at an inhibitory site
      in response to hyperosmotic stress.
AB  - The cysteine aspartyl protease caspase-9 is a critical component of the intrinsic
      apoptotic pathway. Activation of caspase-9 is inhibited by phosphorylation at
      Thr125, which is catalysed by the mitogen-activated protein kinases (MAPKs)
      ERK1/2 in response to growth factors, by the cyclin-dependent protein kinase CDK1
      cyclin B1 during mitosis, and at a basal level by the dual-specificity tyrosine
      phosphorylation regulated protein kinase DYRK1A. Here we show that inhibitory
      phosphorylation of caspase-9 at Thr125 is induced in mammalian cells by
      hyperosmotic stress. This response does not require ERK1/2 or ERK5, but it is
      diminished by ablation of DYRK1A expression by siRNA or chemical inhibition of
      DYRK1A by harmine. Phosphorylation of Thr125 in response to hyperosmotic stress
      is also reduced by chemical inhibition of p38 MAPK and is abolished in p38 alpha(
      /-) mouse embryonic fibroblasts. These results show that both DYRK1A and p38
      alpha play roles in the inhibitory phosphorylation of caspase-9 following
      hyperosmotic stress and suggest a functional interaction between these protein
      kinases. Phosphorylation of caspase-9 at Thr125 may restrain apoptosis during the
      acute response to hyperosmotic stress.

PMID- 19586615
TI  - The internal mechanical functioning of intervertebral discs and articular
      cartilage, and its relevance to matrix biology.
AB  - Degeneration of intervertebral discs and articular cartilage can cause pain and
      disability. Risk factors include genetic inheritance and age, but mechanical
      loading also is important. Its influence has been investigated using miniature
      pressure transducers to measure the distribution of compressive stress (force per
      unit area) within loaded tissue. The technique quantifies stress concentrations,
      and detects regions that behave in a fluid-like manner. Intervertebral discs
      demonstrate a central fluid-like region which normally extends beyond the
      anatomical nucleus pulposus so that the whole disc functions like a "water bed".
      With increasing age, the fluid region shrinks and pressure within it falls.
      Stress concentrations appear in the surrounding anulus fibrosus, with location
      depending on posture. Stress concentrations become large in degenerated discs,
      and are intensified by sustained loading or injury. Articular cartilage never
      exhibits an internal fluid pressure: stress gradients and concentrations normally
      occur within it, and are intensified by sustained loading. Excessive matrix
      stresses can cause pain and progressive damage. They also inhibit matrix
      synthesis and stimulate production of matrix-degrading enzymes. In this way,
      injury to chondroid tissues can initiate a 'vicious circle' of abnormal matrix
      stresses, abnormal metabolism, weakened matrix, and further injury, which
      explains many features of their degeneration.

PMID- 19586614
TI  - Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6.
AB  - Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase
      (MAP3K) that activates multiple mitogen-activated protein kinase (MAPK) pathways
      in response to growth factors, stresses and the pro-inflammatory cytokine, tumor
      necrosis factor (TNF). MLK3 is required for optimal activation of stress
      activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling by TNF,
      however, the mechanism by which MLK3 is recruited and activated by the TNF
      receptor remains poorly understood. Here we report that both TNF and interleukin
      1 beta (IL-1 beta) stimulation rapidly activate MLK3 kinase activity. We observed
      that TNF stimulates an interaction between MLK3 and TNF receptor associated
      factor (TRAF) 2 and IL-1 beta stimulates an interaction between MLK3 and TRAF6.
      RNA interference (RNAi) of traf2 or traf6 dramatically impairs MLK3 activation by
      TNF indicating that TRAF2 and TRAF6 are critically required for MLK3 activation.
      We show that TNF also stimulates ubiquitination of MLK3 and MLK3 can be
      conjugated with lysine 48 (K48)- and lysine 63 (K63)-linked polyubiquitin chains.
      Our results suggest that K48-linked ubiquitination directs MLK3 for proteosomal
      degradation while K63-linked ubiquitination is important for MLK3 kinase
      activity. These results reveal a novel mechanism for MLK3 activation by the pro
      inflammatory cytokines TNF and IL-1 beta.

PMID- 19586616
TI  - Age-related differences of QT interval and autonomic nervous system activity in
      female cynomolgus monkeys.
AB  - INTRODUCTION: Cynomolgus monkeys are used in in vivo toxicological studies to
      evaluate the effects of drug candidates on the cardiovascular system, especially
      the effects of drugs on the QT interval on the electrocardiogram (ECG). Aging is
      reportedly one of the factors influencing the QT interval, but data from old
      monkeys have not been available. METHODS: The ECG parameters, including the QT
      interval and rate-corrected QT intervals calculated using Bazett's formula (QTcB)
      or individual correction factors (QTcI), in old female monkeys (the old group,
      n=7, average age=25.1+/-1.1 years) or young female monkeys (the young group, n=7,
      average age=4.4+/-0.2 years) were assessed by Holter electrocardiogram
      monitoring. The prolongation of QT interval induced by dl-sotalol, a
      representative class III antiarrhythmic drug, was also evaluated. In addition,
      power spectral analysis of heart rate variability was conducted. RESULTS: The QT
      interval in the old group was shorter than that of the young group during the
      dark period. The power spectral analysis of the ECG revealed quite a difference
      in autonomic nervous system activity between old and young animals. The
      prolongations of the QT interval, QTcB and QTcI after oral administration of 3
      mg/kg dl-sotalol in the old group tended to be greater than those in the young
      group, and the QT interval in the old group was significantly longer than that in
      the young group at 1 h after dosing of dl-sotalol. DISCUSSION: The present study
      revealed some of the influences of age on the QT interval in female cynomolgus
      monkeys. There may be age-related differences in the circadian variation of QT
      interval or the drug-induced QT interval prolongation in this species.

PMID- 19586617
TI  - Counter-regulation by atorvastatin of gene modulations induced by L-NAME
      hypertension is associated with vascular protection.
AB  - Statins, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors,
      protect against deleterious effects of chronic nitric oxide inhibition. We aimed
      at determining the genes and pathways involved in the protective effect of statin
      treatment during hypertension. Chronic inhibition of nitric oxide synthesis by
      Nomega-nitro-L-arginine methyl ester (L-NAME) induced accelerated hypertension
      which was slightly reduced by cotreatment with atorvastatin (100 mg/kg/day). Gene
      expression profile of aortic media was strongly modified by atorvastatin
      cotreatment which prevented modulation of many genes regulated by L-NAME
      administration (described in Dupuis, M., Soubrier, F., Brocheriou, I., Raoux, S.,
      Haloui, M., Louedec, L., Michel, J.B., Nadaud, S., 2004. Profiling of aortic
      smooth muscle cell gene expression in response to chronic inhibition of nitric
      oxide synthase in rats. Circulation 110, 867-873). The functional classification
      of these genes highlighted several major biological pathways modulated in aortic
      media by atorvastatin: effectors involved in smooth muscle tone; extracellular
      matrix; intracellular mediators of cell proliferation. Moreover, atorvastatin
      partially prevented arterial wall thickening, TGF-beta pathway activation, MCP-1
      induction and smooth muscle cell proliferation induced by L-NAME treatment
      although blood pressure was only slightly reduced, suggesting mechanisms
      independent of blood pressure levels. The induction of PPARalpha mRNA expression
      by atorvastatin in L-NAME treated rats also suggests that this pathway could
      participate in the protective effect. In conclusion, our data show that
      atorvastatin specifically antagonizes a set of genes modulated by L-NAME-induced
      accelerated hypertension.

PMID- 19586618
TI  - Investigating users' intuitive interaction with complex artefacts.
AB  - This paper examines the role of intuition in the way that people operate
      unfamiliar devices. Intuition is a type of cognitive processing that is often non
      conscious and utilises stored experiential knowledge. Intuitive interaction
      involves the use of knowledge gained from other products and/or experiences. Two
      initial experimental studies revealed that prior exposure to products employing
      similar features helped participants to complete set tasks more quickly and
      intuitively, and that familiar features were intuitively used more often than
      unfamiliar ones. A third experiment confirmed that performance is affected by a
      person's level of familiarity with similar technologies, and also revealed that
      appearance (shape, size and labelling of features) seems to be the variable that
      most affects time spent on a task and intuitive uses during that time. Age also
      seems to have an effect. These results and their implications are discussed.

PMID- 19586619
TI  - Thought suppression failures in combat PTSD: a cognitive load hypothesis.
AB  - The present study investigated the relation between thought suppression of
      emotionally neutral content [i.e., Wegner's (1994) "white bear"], incidental
      traumatic thought intrusion, and skin conductance responses in combat-related
      Posttraumatic Stress Disorder (PTSD). Participants included service members who
      either: a) had PTSD following an Operation Iraqi Freedom deployment; b) were free
      of psychiatric diagnosis following deployment (Combat Equivalent), or c) were pre
      deployed and without psychiatric diagnosis (Pre-Deployed). PTSD Service Members
      reported the greatest intrusion of combat thoughts during the suppression task
      and demonstrated a post-suppression rebound effect with a neutral thought. Non
      specific skin conductance responses indicated that the suppression task was
      related to similar levels of increased sympathetic activity for both the PTSD and
      Pre-Deployed groups, whereas the Combat Equivalent group showed no increased
      activation during thought suppression. Intrusive traumatic thoughts combined with
      failures in neutral thought suppression may be a consequence of increased
      cognitive load in PTSD.

PMID- 19586621
TI  - [Laparoscopic fenestration of a splenic cyst using a single access technique].

PMID- 19586620
TI  - [New trends in the treatment of post-operative pain in general and
      gastrointestinal surgery].
AB  - The correct application of multimodal analgesia appropriate to the pain
      intensity, the characteristics of the surgery and the hospitalisation scheme
      provide the key to improving the management of postoperative pain, which is
      currently still under treated. In highly complex surgeries the best benefit is
      obtained by combining systemic analgesic drugs with regional analgesia
      techniques. Epidural analgesia, not only provides an excellent quality of
      analgesia, but can prevent complications and reduce postoperative morbidity.
      Recently, peripheral blocks and parietal infiltration techniques, with or without
      catheter, have gained prominence in the postoperative analgesia of haemorrhoids
      and hernia repair. All these analgesic techniques are integrated into the concept
      of early postoperative rehabilitation and pursue the objective of minimising the
      side effects associated with the treatment and facilitate the functional recovery
      of the patient. In addition, proper postoperative pain management, not only
      increases the quality of in-patient care but is also a factor to consider in the
      development of chronic post-surgical pain, where the impact is significant and
      impairs the quality of life of the patients.

PMID- 19586622
TI  - [Four years experience with the AEC residents E-Book].
AB  - INTRODUCTION: The introduction of the Spanish Association of Surgeons resident's
      electronic book (AEC-E-Book), has meant that we can perform particular and
      overall assessments of each resident. The objective of this article has been to
      find out the mean health care, scientific and surgical activities according to
      the speciality program. MATERIAL AND METHOD: A register of the activities of
      residents in the AEC-E-Book. The overall activity per year and per rotation has
      been measured. The relationships of assisted interventions performed and their
      level of complexity have been analysed. The mean scientific and health care
      activities and the mean on-call periods per month. RESULTS: A total of 8
      residents have registered their activity in the AEC-E-Book since the year 2004.
      They assisted in a mean of 1514 operations, of which 922 were performed as
      surgeon (62%). They assisted in 185 laparoscopic interventions, of which they
      performed 72 (39%). As surgeon, 864 (94%) of the 922 procedures 64% were level 1,
      75% level 2, and 53% were level 3. They were on-call a mean of 5.75 times per
      month. They attended a total of 21 courses and congresses during residency. They
      took part in 24 presentations and posters, as well as in 6 journal publications
      during residence. CONCLUSIONS: The AEC-E-Book enables the activity of the
      resident to be continually assessed. We have been able to find out the mean
      activities carried out by each resident during a particular rotation and year,
      thus being able to know exactly if they have fulfilled the defined minimums.

PMID- 19586623
TI  - [Acute post-surgical pain. The need for its correct treatment].

PMID- 19586624
TI  - Design and robust tuning of control scheme based on the PD controller plus
      Disturbance Observer and low-order integrating first-order plus dead-time model.
AB  - This paper presents an effective design and robust tuning method for the control
      structure based on a series PD controller and a simple Disturbance Observer. All
      elements of the proposed controller are directly obtained from the low-order
      Integrating First-Order Plus Dead-Time (IFOPDT) model, used to approximate
      essential dynamic characteristics of lag-dominant stable, integrating and
      unstable plants. The structure of the proposed controller is an effective, easy
      to implement and tune, extension of the series PID controller. For the same
      robustness, a better disturbance rejection response is obtained by the proposed
      controller than that of the PID, by adjusting only two parameters with a clear
      meaning. A comparison with well-tuned PIDs, done by simulations, and the
      experimental results, obtained on a real thermal power plant, confirm that high
      performance and robustness are obtained, for dynamic characteristics common to
      industrial processes.

PMID- 19586625
TI  - Management of infected femoral nonunions with a single-staged protocol utilizing
      internal fixation.
AB  - PURPOSE: There are no reported series that specifically deal with repair of
      infected nonunions of the femur with revision internal fixation. We sought to
      determine whether a standardised treatment protocol we have used for 13 patients
      since 1992 results in a high union rate, resolution of infection, and a good
      functional outcome. METHODS: The study cohort included seven male and six female
      patients who presented to the senior author with an infected nonunion of the
      shaft of the femur. Eleven patients with a minimum of 2-year follow-up and
      between the ages of 19 and 75 years (mean 53.2 years) were included and
      evaluated. All patients underwent a single-staged protocol that includes an
      antibiotic "holiday", then treating the infected nonunion with surgical
      debridement and hardware removal, local and systemic antibiotics, revision open
      reduction and internal fixation, and use of supplemental bone grafting. Great
      emphasis at the time of surgery is placed upon aggressive debridement, correction
      of any deformity, and obtaining stable internal fixation. We sought to report our
      success rate of nonunion repair, number of re-interventions, complication rate,
      final knee range of motion, and the ability to eradicate the infection using this
      treatment regimen. RESULTS: At most recent follow-up (mean 5.6, range 2-12
      years), all patients had united and resolved their infections. Ten of the
      patients healed their nonunions with the fixation placed at the time of initial
      revision by us. Five patients required re-interventions to ultimately attain
      fracture union. Four patients had additional bone grafting procedures at the time
      of antibiotic bead removal. One of these four patients, who was later diagnosed
      with a nickel allergy, required three subsequent revision open reduction and
      internal fixations with bone grafting for hardware failure and persistent
      nonunion. A final patient underwent nail dynamisation with achievement of osseous
      union. Only one patient had less than 90 degrees of knee flexion, although he
      previously had an extensor mechanism disruption and had only 15 degrees of
      flexion noted at the time of initial surgery performed by us. CONCLUSION: The
      results of this study indicate that our standard protocol for treatment of
      infected nonunion of the shaft of the femur is reliable at obtaining fracture
      union with a good functional result, while resolving infection despite the
      reliance upon internal fixation.

PMID- 19586626
TI  - Pelvic abscess associated with Haemophilus influenzae bacteremia.

PMID- 19586627
TI  - A valid step in the process: a commentary on Beckstead (2009).

PMID- 19586628
TI  - Participation of 5-lipoxygenase-derived LTB(4) in 4-hydroxynonenal-enhanced MMP-2
      production in vascular smooth muscle cells.
AB  - 5-Lipoxygenase (5-LO) has been suggested as a modulator of atherosclerotic plaque
      instability, however, its role in MMP production in vascular smooth muscle cells
      (VSMC) is still unclear. Thus, this study investigated the role of 5-LO in HNE
      enhanced MMP-2 production in VSMC, and the mechanisms by which this enzyme could
      be activated by HNE. VSMC stimulated with HNE (1 microM) produced MMP-2, which
      was markedly attenuated in 5-LO-deficient VSMC as well as in cells pretreated
      with a FLAP inhibitor, MK886, confirming a role for 5-LO metabolites in HNE
      enhanced MMP-2 production. Related to these results, HNE increased nuclear
      translocation of 5-LO promoting 5-LO activity, which was attenuated not only by
      SB203580, a p38 MAPK inhibitor, but also by PD98059, an ERK inhibitor. In
      parallel, phosphorylation of p38 MAPK and ERK occurred as early as 15 min after
      exposure to HNE, suggesting a potential role for p38 MAPK and ERK pathways in HNE
      induced activation of 5-LO. Among leukotriene (LT) receptor antagonists, U-75302,
      a BLT receptor antagonist, but not MK-571 and Rev-5901, cysLT receptor
      antagonists, showed an inhibitory effect on HNE-enhanced MMP-2 production.
      Moreover, MMP-2 production in VSMC was also significantly increased by LTB(4),
      but not by LTC(4) and LTD(4). Collectively, these data suggest that 5-LO mediates
      HNE-enhanced MMP-2 production via LTB(4)-BLT receptor pathways, consequently
      leading to atherosclerotic plaque instability.

PMID- 19586630
TI  - A confirmatory method for the simultaneous extraction, separation, identification
      and quantification of Tetracycline, Sulphonamide, Trimethoprim and Dapsone
      residues in muscle by ultra-high-performance liquid chromatography-tandem mass
      spectrometry according to Commission Decision 2002/657/EC.
AB  - A rapid confirmatory multi-residue method for the analysis of tetracyclines,
      sulphonamides, trimethoprim and dapsone by UPLC-MS/MS is described. The method is
      able to quantify and confirm the following 19 compounds, oxytetracycline,
      tetracycline, chlortetracycline, doxycycline, sulfadiazine, sulfathiazole,
      sulfapyridine, trimethoprim, sulfamerazine, sulfamethizole, sulfamethazine,
      sulfamethoxypyridazine, sulfamonomethoxine, sulfachlorpyridazine, dapsone,
      sulfamethoxazole, sulfisoxazole, sulfaquinoxaline and sulfadimethoxine. Samples
      are extracted with 0.1M EDTA and acetonitrile, which is then evaporated under a
      stream of nitrogen and reconstituted in water. Following centrifugation and
      filtering, an aliquot is analysed by UPLC-MS/MS using positive electrospray
      ionisation and multiple reaction monitoring. The method is deemed rapid as all
      analytes are extracted by a single extraction technique, with no solid-phase
      extraction clean up required. Validation is according to Commission Decision
      2002/657/EC and was carried out for bovine, porcine, ovine and poultry species.
      Specificity, recovery, repeatability, reproducibility, CCalpha and CCbeta data is
      presented.

PMID- 19586629
TI  - Cilostazol inhibits high glucose- and angiotensin II-induced type 1 plasminogen
      activator inhibitor expression in artery wall and neointimal region after
      vascular injury.
AB  - Increased expression of plasminogen activator inhibitor-1 (PAI-1) in vascular
      tissues is a potential factor linking diabetes to restenosis after percutaneous
      coronary intervention. Recent studies have shown that cilostazol, a selective
      type 3 phosphodiesterase inhibitor, prevents neointimal hyperplasia and in-stent
      thrombosis in patients with diabetes after coronary angioplasty and stent
      implantation. However, the molecular mechanism of this drug has not been fully
      elucidated. We examined whether cilostazol inhibits PAI-1 expression in vascular
      smooth muscle cells (VSMCs) and neointimal hyperplasia. We found that cilostazol
      effectively inhibits angiotensin II-, high glucose- and TGF-beta-stimulated PAI-1
      expression in vivo and in vitro. Cilostazol attenuated PAI-1 expression in
      neointimal regions and inhibited neointimal hyperplasia after balloon injury.
      Cilostazol inhibited PAI-1 expression by multiple mechanisms including
      downregulation of TGF-beta, JNK and p38 signaling pathways. Cilostazol also
      inhibited transactivating activity at the PAI-1 promoter by Smad3, leading to a
      suppression of PAI-1 gene transcription. Taken together with its
      antiproliferative effect on VSMCs, this may explain how cilostazol exerts its
      antithrombogenic effects after angioplasty and stent implantation.

PMID- 19586631
TI  - Size-fractionation of silver nanoparticles using ion-pair extraction in a counter
      current chromatograph.
AB  - Size separation of silver nanoparticles was investigated in counter-current
      chromatography (CCC) based on a unique step-gradient extraction process.
      Carboxylate anions were modified on silver nanoparticles to produce water
      dispersible nanoparticles. The aqueous nanoparticles were readily transferred to
      the organic phase (toluene/hexane=1:1, v/v) together with the phase transfer
      catalyst, tetraoctylammonium bromide (TOAB), owing to the ion-pair adduct
      formation between silver nanoparticle anions and tetraoctylammonium cations.
      Smaller nanoparticles were found to be more readily transferred to the organic
      phase compared to larger nanoparticles. Various concentrations of TOAB in the
      organic elution phase were used in the CCC extraction experiments. It appeared
      that a concentration of 0.02 mM of TOAB was adequate to achieve optimum
      separation and recovery for the aqueous Ag nanoparticle sample (1.5mg) in the CCC
      extraction experiments. Samples of 15.8+/-5.3 nm were separated; the
      distributions of four fractions collected were 13.7+/-1.9, 14.1+/-3.5, 19.2+/
      4.3, and 22.2+/-4.9 nm. Compared with the stepwise extraction performed in this
      study, the step-gradient extractions using CCC provided much better size
      discrimination.

PMID- 19586632
TI  - Determination of competitive adsorption isotherms applying the nonlinear
      frequency response method. Part I. Theoretical analysis.
AB  - In this work adsorption equilibria of binary mixtures are quantified analyzing
      the nonlinear frequency response of a chromatographic column. Local partial
      derivatives of an isotherm model can be estimated for certain steady-states from
      the low frequency asymptotes of the corresponding frequency response functions
      (FRFs). The required FRFs correspond to two different compounds and the type of
      the imposed inlet concentration changes, e.g. periodical inlet concentration
      changes of only one compound or of both of them. For an accurate determination of
      isotherm parameters, it is necessary to approach as close as possible the low
      frequency asymptotic behaviour of these functions. Based on principles valid for
      the FRFs corresponding to the adsorption of a single solute, frequencies needed
      to reach the low frequency asymptotes of the functions of interest for estimating
      competitive isotherms are defined in this paper. The relation between the
      accuracy of the isotherm parameters determined and numbers and types of
      periodical inlet concentration changes and steady-states analyzed is also
      evaluated.

PMID- 19586634
TI  - Determination of competitive adsorption isotherms applying the nonlinear
      frequency response method. Part II. Experimental demonstration.
AB  - This paper demonstrates an experimental application of the nonlinear frequency
      response (FR) method extension to determine adsorption isotherms of binary
      mixtures. This method, based on the analysis of the response of a chromatographic
      column subjected to the sinusoidal inlet concentration changes, is shown to be an
      alternative for isotherm determination. The critical issue related to the
      successful application of the method is to reach experimentally the low frequency
      asymptotic behaviour of the corresponding frequency response functions (FRFs).
      Although, there are different possibilities to perform periodical inlet
      concentration changes, in this paper only simultaneous changes for both
      components were considered. The adsorption of phenol and 2-phenylethanol on
      octadecyl silica was analyzed experimentally using a mixture of methanol and
      water as a solvent. Parameters of competitive isotherms were also estimated for
      comparison using the classical perturbation method. Despite certain differences
      between competitive isotherms estimated with the two methods that were found, the
      obtained results show the potential of the nonlinear FR method for measuring
      competitive isotherms.

PMID- 19586633
TI  - The development of a gas chromatographic-mass spectrometric analytical procedure
      for the determination of lipids, proteins and resins in the same paint micro
      sample avoiding interferences from inorganic media.
AB  - This paper presents a GC-MS analytical procedure for determining proteinaceous
      materials, glycerolipids, natural waxes and terpenoid resins in the same paint
      micro-sample. The procedure is also reliable when high amounts of interfering
      inorganic pigments, dryers and charges are present. The characterisation of
      proteinaceous binders in a paint sample can be subject to analytical
      interferences by inorganic materials. Such materials may form complexes with
      functional groups of proteins, thus preventing their efficient derivatisation,
      which is necessary prior to GC analysis. For this reason an analytical procedure
      has been developed based on two extractions and a clean-up step, in order to
      obtain two fractions: a lipid-resinous fraction and a proteinaceous fraction. The
      lipid-resinous fraction is subjected to salification/saponification assisted by
      microwaves, followed by acidification, extraction, derivatisation and GC-MS
      analysis. The proteinaceous fraction is analysed by GC-MS after hydrolysis and
      derivatisation of the freed amino acids. The desalting step is applied before the
      hydrolysis, and is based on the use of the monolithic sorbent tip technology with
      a C4 stationary phase. Reference paint replicas of egg, casein and animal glue
      were prepared with and without several metals containing pigments, and used to
      develop and validate the analytical procedure. The procedure proved to be
      efficient in desalting the proteinaceous materials both from cations and anions.
      Although non quantitative, it is reliable in the analysis of samples whose
      content of extractable proteins is <1 microg, thus showing it to be suitable for
      the characterisation of paint samples. An example of how the analytical procedure
      was used to characterise a sample from a 15th century panel painting is also
      discussed.

PMID- 19586635
TI  - Rational optimization of the Whelk-O1 chiral stationary phase using molecular
      dynamics simulations.
AB  - Rational in silico optimization of the Whelk-O1 chiral stationary phase (CSP) has
      been carried out based on the chiral recognition mechanism extracted from
      previous molecular dynamics simulations [C.F. Zhao, N.M. Cann, Anal. Chem. 80
      (2008) 2426] of this CSP. Three modified CSPs have been examined. The first two
      are designed to increase selectivity by reducing the docking probability of the
      less retained analyte. The third modified selector reverses the amide bridge to
      introduce a structural motif found in the popular carbamate-derivatized
      polysaccharide CSPs [Y. Okamoto, M. Kawashima, K. Hatada, J. Am. Chem. Soc. 106
      (1984) 5357]. For each modified selector, an atomistic model has been obtained
      through extensive ab initio calculations. The effect of selector modification is
      then evaluated via simulations of the modified interface in the presence of
      target analytes. Simulation results show that the separation factors are
      increased for the modified CSPs but in some cases elution orders are reversed.
      The Whelk-O1 CSP was originally designed to separate naproxen [W.H. Pirkle, C.J.
      Welch, B. LAmm, J. Org. Chem. 57 (1992) 3854]. With this in mind, molecular
      dynamics simulations of naproxen are compared for the original, and the modified,
      selectors.

PMID- 19586636
TI  - Synthesis and aqueous solution properties of novel anionic heterogemini
      surfactants containing a phosphate headgroup.
AB  - The physicochemical properties of aqueous solutions of novel anionic heterogemini
      surfactants (POH-n-ODAm) have been studied on the basis of static/dynamic surface
      tension, fluorescence, dynamic light scattering (DLS) and cryogenic transmission
      electron microscope (cryo-TEM) data. The surfactants are synthesized from oleic
      acid: the hydrocarbon chain (n=6, 8 and 10) is covalently bound to the terminal
      carbonyl group and a phosphate headgroup is introduced to the cis double bond of
      an oleic acid derivative. The static surface tension and fluorescence
      measurements demonstrate that the critical aggregation concentration (cac) is
      decreased significantly with increasing hydrocarbon chain length, resulting from
      the increased hydrophobicity and the increased degree of dissymmetry of the
      surfactants. As is generally seen for gemini surfactants, the measured cac is
      much lower than that of the monomeric phosphate-type surfactant reported
      previously. At concentrations well above the cac, the heterogemini surfactants
      spontaneously form vesicular assemblies in bulk solution, which is confirmed with
      DLS and cryo-TEM measurements.

PMID- 19586637
TI  - Evaluation of adhesion force between functionalized microbeads and protein-coated
      stainless steel using shear-flow-induced detachment.
AB  - Spherical microbeads functionalized with two types of chemical groups (NH(2), OH)
      were chosen as a simplified bacterial model, in order to elucidate the role of
      macromolecular interactions between specific biopolymers and 316 L stainless
      steel, in the frame of biofilm formation in the marine environment. NH(2)
      microbeads were used in their native form or after covalent binding to BSA or
      different representative poly-amino acids. OH microbeads were used in their
      native form. Adhesion force between microbeads and bare or BSA-coated stainless
      steel was quantified at nanoscale. Shear-flow-induced detachment experiments were
      combined with a simplified version of a theoretical model, based on the balance
      of hydrodynamic forces and torque exerted on microbeads. A maximal adhesion force
      of 27.6+/-8.5 nN was obtained for BSA-coated NH(2) microbeads. The high
      reactivity of OH functional groups was assessed (adhesion force of 15.6+/-4.8 nN
      for large microbeads). When charge-conducting stainless steel was coated with
      BSA, adhesion force was significantly lower than the one estimated with the bare
      surface, probably due to an increase in hydrophilic surface properties or
      suppression of charge transfer. The mechanism for microbead detachment was
      established (mainly rolling). The flow chamber and the associated theoretical
      modelling were demonstrated to be a relevant approach to quantify nanoscale
      forces between interacting surfaces.

PMID- 19586638
TI  - Single-prolonged stress induces apoptosis in the amygdala in a rat model of post
      traumatic stress disorder.
AB  - OBJECTIVE: To detect the apoptosis-related Bax and Bcl-2 gene expression and
      apoptotic cell death in the amygdala region in the single-prolonged stress (SPS)
      rats. METHODS: A total of 100 male Wistar rats were randomly divided into a
      normal control group and SPS groups of 1d, 4d, 7d, and 14d. The expression of Bax
      and Bcl-2 was detected using immunohistochemistry and Western Blotting; TUNEL
      staining and double-labeled flow cytometry (FCM) were employed for the detection
      and quantification of the apoptotic cells in the amygdala; morphological change
      of the subcellular structure in amygdala was observed by using the transmission
      electron microscopy (TEM). RESULTS: The ratio of Bax/Bcl-2 peaked at SPS 4d and
      then gradually decreased. The apoptosis peaked at SPS 4d. The TUNEL-positive
      cells were found in each SPS group and the TUNEL-positive cells rate peaked at
      SPS 4d. The morphological change of amygdala cells in each SPS group bears
      typical apoptotic characteristics. CONCLUSIONS: In the SPS rat brain, we found
      apoptotic process in the amygdala region which may relate to the pathogenesis of
      amygdala abnormal function in PTSD.

PMID- 19586639
TI  - Carnitine protects the intestine against reperfusion injury in rats.
AB  - BACKGROUND: Although the negative effects of ischemia on anastomotic healing have
      been shown in many studies, there is no adequate information on the effects of
      reperfusion injury. Therefore, in this study, we investigated the effect of
      ischemia-reperfusion (IR) injury on intestinal anastomosis and the protective
      efficiency of carnitine in an experimental relatively short intestinal ischemia
      and long duration reperfusion model. METHODS: Animals were divided into three
      groups (n=14). Each group was separated into two subgroups. In subgroups A,
      morphologic injury and the number of perfused intestinal muscular microvessels
      were analyzed to show "no-reflow phenomenon." Intestinal resection and
      anastomosis were performed in subgroups B. Carnitine group (IRCarG) received 200
      mg/kg intravenous carnitine 2 min prior to reperfusion. Malonyldialdehyde, nitric
      oxide levels in tissue and blood, collagen levels, bursting pressures, and
      histopathologic evaluation of anastomosis were measured in subgroups B. RESULTS:
      Morphologic damage was statistically lower, number of perfused microvessels and
      epithelial regeneration were statistically higher in IRCarG, compared with
      ischemia-reperfusion group (P=0.03, P=0.008, P=0.05, respectively). CONCLUSION:
      Carnitine application prior to reperfusion may reduce the severity of the
      reperfusion injury by preventing the occurrence of no-reflow phenomenon, increase
      the number of perfused microvessels in the ischemic intestine, and may improve
      epithelial regeneration in intestinal anastomosis.

PMID- 19586641
TI  - [Annular granuloma and diabetes mellitus].

PMID- 19586642
TI  - Height, ethnicity, and the incidence of diabetes: the San Antonio Heart Study.
AB  - Mexican Americans are more obese and have more diabetes than non-Hispanic whites,
      but are also shorter. Height is used in some diabetes prediction models.
      Therefore, we examined the effect of height on the relationship between ethnicity
      and incident diabetes. Incident diabetes was ascertained in 1730 participants in
      the San Antonio Heart Study (age range, 25-64 years) after 7.4 years of follow
      up. Height predicted diabetes in neither men (odds ratio [OR] x 1 SD, 1.14 [0.85
      1.51]) nor women (OR x 1 SD, 0.88 [0.70-1.11]) after adjusting for age and
      ethnicity. The area under the receiver operating characteristic curve for
      predicting diabetes of a model that included waist circumference (in men, 0.775;
      in women, 0.781) was similar to that of models that included waist circumference
      + height (in men, 0.775, P = .702; in women, 0.783, P = .680) or waist-to-height
      ratio (in men, 0.764, P = .161; in women, 0.783, P = .619). The OR of incident
      diabetes according to ethnicity was lower in the model that was adjusted for the
      waist-to-height ratio than in the model that accounted only for waist
      circumference (in women, 1.45 [0.86-2.46] vs 1.84 [1.10-3.08], P < .001; in men,
      2.00 [1.11-3.58] vs 2.74 [1.52-4.95], P < .001). In conclusion, the addition of
      height to adjust waist circumference does not increase the ability of waist
      circumference to predict diabetes, but may be useful in exploring differences in
      diabetic risk between populations of different race/ethnicity.

PMID- 19586643
TI  - Decreased enzyme activity and contents of hepatic branched-chain alpha-keto acid
      dehydrogenase complex subunits in a rat model for type 2 diabetes mellitus.
AB  - The mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC) is
      responsible for the committed step in branched-chain amino acid catabolism. In
      the present study, we examined BCKDC regulation in Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats both before (8 weeks of age) and after (25 weeks of age) the
      onset of type 2 diabetes mellitus. Long-Evans Tokushima Otsuka (LETO) rats were
      used as controls. Plasma branched-chain amino acid and branched-chain alpha-keto
      acid concentrations were significantly increased in young and middle-aged OLETF
      rats. Although the hepatic complex was nearly 100% active in all animals, total
      BCKDC activity and protein abundance of E1alpha, E1beta, and E2 subunits were
      markedly lower in OLETF than in LETO rats at 8 and 25 weeks of age. In addition,
      hepatic BCKDC activity and protein amounts were significantly decreased in LETO
      rats aged 25 weeks than in LETO rats aged 8 weeks. In skeletal muscle, E1beta and
      E2 proteins were significantly reduced, whereas E1alpha tended to increase in
      OLETF rats. Taken together, these results suggest that (1) whole-body branched
      chain alpha-keto acid oxidation capacity is extremely reduced in OLETF rats
      independently of diabetes development, (2) the aging process decreases BCKDC
      activity and protein abundance in the liver of normal rats, and (3) differential
      posttranscriptional regulation for the subunits of BCKDC may exist in skeletal
      muscle.

PMID- 19586645
TI  - Non-modular polyketide synthases in myxobacteria.
AB  - Myxobacteria are prolific producers of a wide variety of secondary metabolites.
      The vast majority of these compounds are complex polyketides which are
      biosynthesised by multimodular polyketide synthases (PKSs). In contrast, few
      myxobacterial metabolites isolated to date are derived from non-modular PKSs, in
      particular type III PKSs. This review reports our progress on the
      characterisation of type III PKSs in myxobacteria. We also summarize current
      knowledge on bacterial type III PKSs, with a special focus on the evolutionary
      relationship between plant and bacterial enzymes. The biosynthesis of a quinoline
      alkaloid in Stigmatella aurantiaca by a non-modular PKS is also discussed.

PMID- 19586644
TI  - Asymmetric dimethylarginine association with antioxidants intake in healthy young
      adults: a role as an indicator of metabolic syndrome features.
AB  - The purpose of this study was to evaluate the potential associations between
      serum asymmetric dimethylarginine (ADMA) and several anthropometric, biochemical,
      and lifestyle features in healthy young adults, emphasizing on the putative
      effects of the antioxidant intake on ADMA concentrations. Anthropometric and
      blood pressure measurements as well as lifestyle features and antioxidant intake
      were analyzed in 93 healthy young adults aged 18 to 34 years. Fasting blood
      samples were collected for the measurement of glucose, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triacylglycerols, and ADMA concentrations, as well as erythrocyte glutathione
      peroxidase activity. Nail samples were collected for the analysis of selenium and
      zinc concentrations. Values of body mass index (P = .004), waist circumference (P
      = .008), waist-to-height ratio (P = .046), systolic blood pressure (P < .001),
      serum glucose (P < .001), and nail selenium (P = .004) and zinc (P = .018) were
      significantly different between subjects with serum ADMA higher and lower than
      the median (cutoff, 458 nmol/L). Furthermore, ADMA showed a positive association
      with several adiposity markers such as body weight (P < .001), body mass index (P
      < .001), waist circumference (P = .006), waist-to-height ratio (P = .020), body
      fat mass (P = .001), systolic blood pressure (P = .001), and serum glucose (P <
      .001), whereas erythrocyte glutathione peroxidase activity (P = .021) and nail
      selenium (P = .040) and zinc values (P = .013) were statistically significant
      negative predictors of ADMA concentrations. In conclusion, ADMA seems to be
      related with selenium and zinc status and several anthropometric and biochemical
      measurements linked to metabolic syndrome in apparently healthy young adults.
      These findings support a role for antioxidant/trace element intake in the
      modulation of ADMA, whose assessment may be a marker of metabolic syndrome
      manifestations.

PMID- 19586646
TI  - Generation and efficacy evaluation of a recombinant adenovirus expressing the E2
      protein of classical swine fever virus.
AB  - Classical swine fever virus (CSFV) is the causative agent of classical swine
      fever (CSF), which causes significant economic losses to the pig industry
      worldwide. The E2 glycoprotein of CSFV is the main target for neutralizing
      antibodies. This study was aimed to develop a recombinant human adenovirus type 5
      expressing the CSFV E2 gene (rAdV-E2) and evaluate its efficacy in rabbits and
      pigs. The results showed that the rabbits and the pigs immunized with the rAdV-E2
      developed high-level CSFV-specific neutralizing antibodies. The rAdV-E2-immunized
      rabbits were protected from fever induced by infection with C-strain, which is
      pathogenic to the rabbit, and the rAdV-E2-immunized pigs were protected from
      lethal challenge with highly virulent Shimen strain. This indicates that the
      recombinant adenovirus can be an attractive candidate vaccine for preventing CSF.

PMID- 19586647
TI  - [Dr Le Fort and IMRAD].

PMID- 19586648
TI  - [Nasoethmoidal psammomatoid cemento-ossifiying fibroma with intraorbital
      extension].
AB  - INTRODUCTION: Psammomatoid cemento-ossifying fibroma (PCOF) is a rare benign
      fibro-osseous lesion. It affects the maxilla, the nasal cavity, paranasal
      sinuses, and the ethmoid. It is slow-growing, progressive, and benign but it can
      be locally extended and mimic a malignant tumor. OBSERVATION: We report the
      unusual case of a 36-year-old woman with a nasal and ethmoid PCOF with orbital
      and endocranial extension. The tumor was revealed by exophthalmia and nasal
      obstruction. The diagnosis was proven histologicaly on biopsies. The treatment
      was transfacial surgery. There was no recurrence 1 year later. DISCUSSION:
      Intraorbital and endocranial extension of PCOF are rare aggressive behaviours.
      Histologically, the differential diagnosis is difficult between fibrous dysplasia
      or psammomatoid meningioma. Complete surgical excision is necessary to prevent
      recurrence.

PMID- 19586650
TI  - Acoustic resonance scattering from a multilayered cylindrical shell with
      imperfect bonding.
AB  - The method of wave function expansion is adopted to study the three dimensional
      scattering of a time-harmonic plane progressive sound field obliquely incident
      upon a multi-layered hollow cylinder with interlaminar bonding imperfection. For
      the generality of solution, each layer is assumed to be cylindrically
      orthotropic. An approximate laminate model in the context of the modal state
      equations with variable coefficients along with the classical T-matrix solution
      technique is set up for each layer to solve for the unknown modal scattering and
      transmission coefficients. A linear spring model is used to describe the
      interlaminar adhesive bonding whose effects are incorporated into the global
      transfer matrix by introduction of proper interfacial transfer matrices.
      Following the classic acoustic resonance scattering theory (RST), the scattered
      field and response to surface waves are determined by constructing the partial
      waves and obtaining the non-resonance (backgrounds) and resonance components. The
      solution is first used to investigate the effect of interlayer imperfection of an
      air-filled and water submerged bilaminate aluminium cylindrical shell on the
      resonances associated with various modes of wave propagation (i.e.,
      symmetric/asymmetric Lamb waves, fluid-borne A-type waves, Rayleigh and
      Whispering Gallery waves) appearing in the backscattered spectrum, according to
      their polarization and state of stress. An illustrative numerical example is also
      given for a multi-layered (five-layered) cylindrical shell for which the
      stiffness of the adhesive interlayers is artificially varied. The sensitivity of
      resonance frequencies associated with higher mode numbers to the stiffness
      coefficients is demonstrated to be a good measure of the bonding strength.
      Limiting cases are considered and fair agreements with solutions available in the
      literature are established.

PMID- 19586649
TI  - Comment on: Failure of a new antivenom to treat Echis ocellatus snake bite in
      rural Ghana: the importance of quality surveillance.

PMID- 19586651
TI  - Application of nanosilver surface modification to RO membrane and spacer for
      mitigating biofouling in seawater desalination.
AB  - Biofouling is one the most critical problems in seawater desalination plants and
      science has not yet found effective ways to control it. Silver compounds and ions
      are historically recognized for their effective antimicrobial activity.
      Nanosilver particles have been applied as a biocide in many aspects of
      disinfection, including healthcare products and water treatment. This study
      proposes an innovative biofouling control approach by surface modification of the
      RO membrane and spacer with nanosilver coating. A chemical reduction method was
      used for directly coating nanosilver particles on the membrane sheet and spacer.
      The surface-modified membrane and spacer were tested for their antifouling
      performance in a cross-flow flat-sheet membrane cell, which is a part of a pilot
      plant in Wukan desalination plant. The silver-coating membranes and spacers,
      along with an unmodified membrane sheet, were tested in the membrane cell and
      compared on the basis of their antifouling performance. Permeate flux decline and
      salt rejection was continuously monitored through the testing period. Meanwhile
      regrowth of microbial populations on the membrane cell was quantified by a unique
      microbial counting every three to four days. The results showed that both silver
      coated membrane (Ag-cM) with uncoated spacer and silver-coated spacer (Ag-cS)
      with uncoated membrane performed better than the unmodified membrane and spacer
      (Un-MS), in terms of much slower decrease in permeate flux and TDS rejection.
      However, the effect of silver-coated spacer on antimicrobial activity was more
      lasting. In the silver-coated spacer test, there was almost no multiplication of
      cells detected on the membrane during the whole testing period. Besides, the
      cells adhering to the membrane seemed to lose their activity quickly. According
      to the RO performance and microbial growth morphology, the nanosilver coating
      technology is valuable for use in biofouling control in seawater desalination.

PMID- 19586652
TI  - Serum levels of organochlorine pesticides in healthy adults from five regions of
      Spain.
AB  - The aim of this study was to measure of serum levels of p,p'-dichlorodiphenyl
      trichloroethane (p,p'-DDT), p,p'-dichlorodiphenyl dichlorethylene (p,p'-DDE),
      beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) in healthy
      adults in Spain. Furthermore, we also analyzed these levels according to dietary,
      other lifestyle factors and anthropometric characteristics. We measured the
      concentrations of such organochlorine pesticides (OCPs) in serum samples
      collected during 1992-1996 from 953 subjects aged 35-64 years, they were
      residents of five Spanish regions, they were randomly selected from the European
      Prospective Investigation into Cancer and Nutrition (EPIC) cohort. OCPs were
      determined by means of gas chromatography with electron-capture detection (GC
      ECD). The most frequent compound found in serum was p,p'-DDE, present in 98% of
      the samples, followed by HCB and beta-HCH, found in 89% and 77% of samples,
      respectively, while p,p'-DDT could be measured only in 26% of subjects. The
      geometric means of serum concentrations (ng/g lipid) were 822 for p,p'-DDE, 167
      for beta-HCH, and 379 for HCB. The concentrations of all OCPs were positively
      associated with age and body mass index, and decreased along the period of blood
      collection. No association was found between OCPs levels and dietary factors. The
      concentrations of p,p'-DDE and beta-HCB were higher in Murcia, one of southern
      regions, most likely associated with intensive past use of pesticides related to
      agricultural practices, while higher levels of HCB were found in Navarra, located
      in the north, maybe due to industrial use rather than agricultural application.

PMID- 19586653
TI  - Periurethral non-animal stabilized hyaluronic acid/dextranomer injections:
      efficacy and formation of granuloma/sterile abscess.

PMID- 19586654
TI  - Urinary prostate cancer 3 test: toward the age of reason?
AB  - The prostate cancer 3 (PCA3) gene was discovered in 1999, on the basis of
      differential expression between cancer and noncancerous prostate tissue.
      Including the first study published in 2003, 11 clinical studies have evaluated
      its utility for the diagnosis of prostate cancer by measuring the number of PCA3
      RNA copies in urine enriched with prostate cells. Although the sensitivity of the
      PCA3 test was less than that of serum prostate-specific antigen (PSA), its
      specificity appeared to be much better, particularly in patients with a previous
      negative biopsy. Recent studies also have suggested that this test could be used
      to predict cancer prognosis.

PMID- 19586655
TI  - Contemporary patients with LUTS/BPH requiring prostatectomy have long-term
      history of treatment with alpha1-blockers and large prostates compared with past
      cases.
AB  - OBJECTIVES: To retrospectively investigate the characteristics of patients with
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia for which
      surgery was needed during the past 20 years. In particular, the chronologic
      change in prostate volume at surgery and the status of alpha(1)-blocker use
      before surgery and its duration were studied. METHODS: The data from 371
      consecutive patients with lower urinary tract symptoms/benign prostatic
      hyperplasia who had undergone surgery in our institute from 1987 through 2006
      were retrospectively analyzed. The number of surgeries, type of surgical
      procedure, content and duration of medical treatment of lower urinary tract
      symptoms/benign prostatic hyperplasia before surgery, prostate volume on
      transrectal ultrasonography at baseline and at surgery, and the weight of the
      removed tissue were determined from the medical charts. RESULTS: The number of
      surgeries suddenly began to decrease between 1987 and 1990 and again from 1991 to
      1994, probably owing to the introduction of 2 nonselective alpha(1)-blockers at
      those times in Japan. The percentage of use of alpha(1)-blockers before surgery
      and the duration of use increased in each period. More than 80% of recent
      patients had received alpha(1)-blockers before surgery, with an average duration
      of 3 years. Recent patients had a large prostate volume at baseline and at
      surgery compared with previous patients. Corresponding to the large prostate,
      open subcapsular prostatectomy was indicated in 18% of the recent patients.
      CONCLUSIONS: Patients with surgical treatment after long-term use of alpha(1)
      blockers had large prostates at baseline and at surgery. Although alpha(1)
      blockers delayed the need for surgery by a few years, patients with a large
      prostate volume might finally need to undergo surgery.

PMID- 19586657
TI  - HPV vaccine for all.

PMID- 19586659
TI  - The influence of wind on the water age in the tidal Rappahannock River.
AB  - Wind plays an important role in regulating mixing/stratification, estuarine
      circulation, and transport timescale in estuaries. A three-dimensional model was
      used to investigate the effect of wind on transport time by using the concept of
      water age (WA) in the tidal Rappahannock River, a western tributary of the
      Chesapeake Bay, USA. The model was calibrated for water level, current, and
      salinity. A series of experiments regarding the effects of wind on WA was
      conducted under various dynamic conditions. The effect of wind on transport
      timescale depends strongly on the competition between the wind and buoyancy
      forcings, and on the pre-status of the circulation. A down-estuary wind generally
      decreases WA along the estuary. An up-estuary wind increases WA substantially
      because it changes the vertical mixing and estuarine circulation more
      significantly. When the buoyancy forcing increases, the up-estuary wind effect
      decreases whereas the down-estuary wind effect increases. A 2-day period wind
      pulse with a maximum speed of 15 ms(-1) can alter WA for 3 days; but the wind
      influence on WA lasts up to 40 days in the simulation. Both local and non-local
      wind forcings alter WA distribution. The local wind enhances vertical mixing and
      changes the gravitational circulation in the downstream portion of the estuary
      whereas it enhances transport in the freshwater portion of the estuary.
      Consequently, the local wind has a significant impact on WA distribution. In
      contrast, the non-local wind does not change the gravitational circulation
      significantly by imposing setup (setdown) of water level at the open boundary,
      resulting in a lesser impact on WA distribution.

PMID- 19586658
TI  - Distribution and contamination of trace metals in surface sediments of the East
      China Sea.
AB  - The distributions, contamination status and annual sedimentation flux of trace
      metals in surface sediments of the East China Sea (ECS) were studied. Higher
      concentrations of the studied metals were generally found in the inner shelf and
      the concentrations decreased seaward. The sequences of the enrichment factor (EF)
      of the studied metals are Cu>Mn>Ni>Zn>Pb>Fe. The values of EF suggest that the
      metals contamination in the middle and outer shelves of the ECS is still minor.
      The annual sedimentation fluxes of trace metals in the ECS were: Fe, 3.48 x
      10(7)t/y; Mn, 9.07 x 10(5)t/y; Zn, 1.08 x 10(5)t/y; Ni, 4.48 x 10(4)t/y; Pb, 4.32
      x 10(4)t/y and Cu, 3.1 x 10(4)t/y, respectively. Approximately 55-70% and 10-17%
      of the sedimentation fluxes of trace metals were deposited in the inner shelf and
      the Changjiang estuarine zone.

PMID- 19586660
TI  - To unfold a hidden epidemic: prevalence of child maltreatment and its health
      implications among high school students in Guangzhou, China.
AB  - OBJECTIVE: This study investigated the prevalence of child maltreatment as
      perpetrated by parents, its associated health outcomes, and its resilient factors
      among high school students in China. METHODS: A multi-level stratified random
      school-based survey was conducted in 2005. Twenty four high schools were randomly
      chosen from eight districts in Guangzhou, South China (three from each district).
      Two classes were randomly selected from each of Form 1 to Form 3 (aged 12-16) in
      each selected school. Data from 6,593 students were analyzed. A number of locally
      validated tools were used to measure various types of maltreatment as well as
      physical and psychological conditions of students. RESULTS: The half-year
      prevalence of psychological aggression, minor physical maltreatment, severe
      physical maltreatment, and very severe physical maltreatment were 78.3%, 23.2%,
      15.1%, and 2.8% respectively; while the half-year prevalence of sexual abuse was
      .6%. Maltreated students were more likely to report physical and psychological
      problems, and a positive relationship was also found between the severity of
      maltreatment and the likelihood of negative health outcomes. Male gender or
      having higher levels of social support and life satisfaction were identified as
      resilient factors to physical health of maltreated students. CONCLUSIONS: Child
      maltreatment as perpetrated by parents is common among high school students in
      Guangzhou, China. More public education programs are needed to raise public
      awareness of this problem. Intervention programs that target at improving social
      support and life satisfaction of students are potentially beneficial.

PMID- 19586662
TI  - The DNA sequence selectivity of maltolato-containing cisplatin analogues in
      purified plasmid DNA and in intact human cells.
AB  - Cisplatin analogues with an attached DNA binding moiety have a higher affinity
      for DNA, but often suffer from poor aqueous solubility. In this study we examined
      the DNA sequence specificity of more soluble cisplatin analogues containing the
      maltolato leaving group in both purified DNA and in intact human cells. In both
      environments the DNA sequence specificity of these analogues was very similar to
      cisplatin. However, in purified DNA a higher concentration of the two maltolato
      containing analogues was needed to achieve a similar level of DNA damage as
      cisplatin. This difference in reactivity was not observed in intact cells as the
      two maltolato-containing complexes were capable of producing a similar level of
      damage as cisplatin at comparable concentrations. This was consistent with the
      IC(50) values obtained for both cisplatin and the maltolato compounds which were
      also similar. This study indicated that maltolato can be utilised as the leaving
      group to increase the aqueous solubility of cisplatin analogues without reducing
      their biological activity.

PMID- 19586661
TI  - Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T
      cell activation.
AB  - The mammalian target of rapamycin (mTOR) is an evolutionarily conserved kinase
      which plays a role in integrating environmental cues. mTOR signals via two
      complexes: TORC1, which contains the Regulatory Associated Protein of TOR
      (raptor), and TORC2, which contains the Rapamycin-insensitive Companion of TOR
      (rictor). The immunosuppressive/anti-cancer agent rapamycin inhibits TORC1
      function by disrupting the mTOR-raptor interaction. In an effort to understand
      the downstream consequences of TORC1 activation in T cells we performed a
      proteomic analysis of raptor binding proteins. Using this approach we have
      identified Hsp90 as an activation-induced binding partner of raptor in T cells.
      Pharmacologic inhibition of Hsp90 leads to a decrease in raptor expression and
      TORC1 activity. Furthermore, full T cell activation during Hsp90 blockade leads
      to T cell tolerance in the form of anergy. Overall, our findings suggest that
      Hsp90 inhibitors might represent a novel means of promoting T cell tolerance.

PMID- 19586656
TI  - Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against
      cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final
      analysis of a double-blind, randomised study in young women.
AB  - BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was
      immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18
      infections, and associated precancerous lesions in an event-triggered interim
      analysis of the phase III randomised, double-blind, controlled PApilloma TRIal
      against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in
      the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at
      months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for
      efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC,
      included all women receiving at least one vaccine dose, regardless of their
      baseline HPV status; represents the general population, including those who are
      sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of
      oncogenic HPV infection at baseline; represents women before sexual debut;
      vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine
      efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was
      associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and
      DNA negative at baseline and month 6 for the corresponding type (ATP-E). This
      trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean
      follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against
      CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary
      analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV
      type was assigned in lesions infected with multiple oncogenic types (ATP-E
      cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was
      30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive.
      Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0%
      (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12
      non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross
      protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in
      the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high
      efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV
      types and substantial overall effect in cohorts that are relevant to universal
      mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

PMID- 19586663
TI  - Identification of low HBV-DNA levels by nucleic acid amplification test (NAT) in
      blood donors.
AB  - OBJECTIVE: To evaluate the presence of HBV-DNA in 22,765 consecutive blood
      donors, who donated blood in the period from January 2006 to August 2007 at a
      transfusion centre in Lazio, a region in central Italy with low HBV endemicity.
      METHODS: Each donation was individually tested using immunoenzymatic assays and
      nucleic acid amplification technologies (NAT). Samples that were reactive to
      generic NAT, Procleix Ultrio Assay were tested for HBV-DNA, HCV-RNA and HIV1-RNA
      by Discriminatory Procleix Ultrio NAT Assay. In samples that were reactive to
      generic NAT and negative for HBsAg, HCV-RNA and HIV1-RNA, HBV-DNA was further
      tested using Cobas TaqMan and an in-house nested PCR following an
      ultracentrifugation step. Sequence analysis confirmed HBV-DNA positivity.
      RESULTS: Generic NAT identified 31 (0.13%) reactive sera. HBV-DNA discriminatory
      NAT identified 15 positive sera; HBsAg was positive in 12 sera. Of the 5 generic
      NAT-reactive/discriminatory NAT-negative/HBsAg-negative sera and of the 3 HBsAg
      negative/HBV-DNA discriminatory NAT-positive sera, 7 were positive to Cobas
      TaqMan or the in-house PCR after ultracentrifugation. The overall HBV-DNA
      positivity was 0.083% [19 of 22,765 donors: 12 HBsAg-positive (HBV-DNA range
      10(2)-10(4) IU/mL), 7 HBsAg-negative/anti-HBc positive (HBV-DNA< 6 IU/mL)].
      CONCLUSIONS: For blood transfusion safety, the significance of the finding of
      very low HBV-DNA levels should be further investigated. Our data indicate that in
      areas with a low HBV endemicity, single NAT assays may not always identify blood
      donations with very low HBV-DNA levels.

PMID- 19586664
TI  - Preeclampsia--a placenta developmental biology perspective.
AB  - There are abundant theories in the scientific literature that propose a range of
      pathophysiological pathways for preeclampsia. In this review we discuss some of
      the contributions made to this field from the perspective of a placental
      developmental biology laboratory. We discuss an underlying immune component of
      preeclampsia associated with expression of HLA-G and also a beneficial function
      of decidual NK cells. We conclude by summarizing newer findings regarding the
      anti-angiogenic expression of soluble fms-like tyrosine kinase (sFlt-1) and its
      role in the development of preeclampsia.

PMID- 19586666
TI  - Cervicofacial nontuberculous mycobacterium lymphadenitis in children: is surgery
      always necessary?
AB  - INTRODUCTION: The optimal treatment of cervicofacial nontuberculous mycobacterium
      lymphadenitis (CFNTB) in children is yet to be established. There is a general
      consensus that surgical excision results in a definitive resolution of the
      disease. The main aim of surgery is to remove affected nodes so that they do not
      discharge through the skin. Recently there are some investigators who are
      reporting successful antibiotic treatment and advocating medical therapy as the
      first line treatment. METHODS: 16 children consecutively presenting to
      otolaryngology in a tertiary referral centre over an 8-year period with CFNTB.
      Inclusion criteria were chronic cervicofacial lymphadenitis with either: (1) a
      culture positive for atypical mycobacteria (from either a lymph node or fine
      needle aspirate (FNA) specimen); or (2) acid-fast bacilli identified (from either
      a lymph node or FNA specimen); or (3) post excision histological findings
      consistent with mycobacterial infection (i.e. non-caseating granulomas) in the
      absence of other clinical features suggestive of other granulomatous conditions.
      Lesions with superficial skin change were treated preferentially with surgery.
      Children presenting with lymph nodes contained deep to sternocleidmastoid were
      assessed with FNA cytological and microbiological analysis and MRI or CT, and
      treated preferentially with antibiotics or watchful waiting. RESULTS: 4 children
      (2 culture positive, 2 with acid-fast bacilli on needle aspirate) presented with
      lymphadenopathy deep to sternocleidmastoid and were managed non-surgically. All 4
      resolved without cutaneous involvement. 11 children with a clinical presentation
      of CFNTB underwent complete excision of all involved nodes for superficial
      lesions (6 were culture positive, and all had granulomatous histology). None
      recurred. 1 patient presented late with a mature, discharging parotid sinus,
      which was managed with watchful waiting as the lesion was clinically close to
      natural resolution. CONCLUSIONS: Depth at presentation may help decide which
      patients with CFNTB can be treated non-surgically without cutaneous sequelae. We
      propose that a watch and wait management is an option for deep nodes.

PMID- 19586667
TI  - Transforming growth factor-beta receptor type 1 (TGFBR1) is not associated with
      non-syndromic cleft lip with or without cleft palate in patients of Central
      European descent.
AB  - OBJECTIVE: Transforming growth factor-beta (TGF-beta) type 1 receptor (also known
      as activin receptor-like kinase 5, ALK5) is expressed in palatal tissue during
      embryogenesis. Experimental studies in transgenic mice with a genetic deletion of
      Alk5 showed that TGF-beta type 1 receptor is required for upper lip and midline
      fusion of the hard and soft palate. In humans, association of TGF-beta type 1
      receptor gene (TGFBR1) and the development of non-syndromic cleft lip with or
      without cleft palate (NSCL/P) had been observed in a multiethnic sample of
      Chinese, Philippine, Indian and Turkish families. In order to re-evaluate the
      relevance of these findings, we carried out a family-based association study
      among 218 NSCL/P families of Central European descent. METHODS: Genomic DNA was
      obtained from peripheral blood of 218 complete parent-offspring triads with
      NSCL/P. The sample comprised 14 patients with cleft lip only (CLO) and 204
      patients with cleft lip and palate (CLP). Genotyping and transmission
      disequilibrium test (TDT) were performed on all 218 triads with a total of 17
      tagging single-nucleotide polymorphisms (SNPs). We also performed testing for
      extended haplotypes and a log-linear model by Weinberg was used to screen parent
      of-origin effects. Furthermore the use of estimates for the relative risks (RR)
      of Weinberg's model was obtained. RESULTS: TDT analysis revealed no significant
      transmission distortion, neither at the level of individual markers nor at the
      level of haplotypes. Similarly negative results were obtained when we restricted
      our analysis to the subgroup of patients with CLP (n=204). Relative risk
      calculations (RR) of the children's and mothers' genotypes obtained negative
      results, after correction of p-values for multiple testing. Likewise application
      of Weinberg's log-linear model did not find any evidence for parent-of-origin
      effects in our sample. CONCLUSION: Despite the ample evidence supporting the role
      of TGF-beta type 1 receptor as a critically important and widespread
      morphogenetic regulator of craniofacial development in murine models, our results
      do not support TGFBR1 as major risk factor for NSCL/P in patients of Central
      European descent.

PMID- 19586665
TI  - Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N
      terminal kinase activation.
AB  - Apolipoprotein E (apoE)-induced activation of low-density lipoprotein receptor
      (LDL) family members reduces inflammatory responses by suppressing c-Jun N
      terminal kinase (JNK) activation. We aimed to identify which specific receptor
      family member mediates the effect of apoE on inflammation in primary cultures of
      microglia. Low-density lipoprotein receptor-related protein 1 (LRP1)-deficient
      (LRP1-/-) microglia were derived from mice using tissue-specific loxP/Cre
      recombination. Using a peptide formed from the receptor-binding region of apoE
      (EP), we found that LRP1 mediates the effects of apoE on microglial inflammation.
      Microglial LRP1 was also essential for EP to suppress JNK activation induced by
      lipopolysaccharide.

PMID- 19586668
TI  - Responses of lake bacterioplankton activities and composition to the herbicide
      diuron.
AB  - The direct effects of pesticides on aquatic bacteria are poorly known. We
      experimentally investigated the direct effects of diuron (herbicide) on the
      composition and activities of lake bacterioplankton, using Denaturing Gradient
      Gel Electrophoresis (DGGE), cloning/sequencing, and flow cytometry with dyes that
      allow detection of dead cells, cells with depolarized membranes and cells with
      esterase activity (for physiological state). Generally, diuron had negative
      impacts on bacterial viability and abundance. Bacterial production strongly
      correlated with ammonium in controls, but not in diuron-treated samples. Moreover
      the increase in nitrate concentration with the proportion of dead bacteria was
      significantly higher in controls, providing evidence not previously shown for
      natural communities, that diuron may alter the mineralization of organic matter
      and nitrification. A picocyanobacteria and members of the family
      Flavobacteriaceae, known to degrade complex polymeric organic matter in aquatic
      systems were negatively affected by diuron. Except that, the DGGE banding
      patterns in controls and in polluted samples were generally similar, suggesting
      no perceptible susceptibility of major bacterial groups, and contrasting with
      previous reports that diuron has a strong impact on bacterial community
      composition. Our data suggest that diuron may affect functioning of aquatic
      systems through negative impacts on some bacterial phylotypes and bacterial
      cycling of nitrogen.

PMID- 19586669
TI  - Transcript profiling and DNA damage in the European eel (Anguilla anguilla L.)
      exposed to 7,12-dimethylbenz[a]anthracene.
AB  - The molecular responses induced during and after an acute exposure to 7,12
      dimethylbenz[a]anthracene (DMBA) were analysed in liver, gill and blood cells of
      juvenile Anguilla anguilla with the aim of developing molecular biomarkers of
      environmental PAH pollution. Changes in the mRNA expression levels of the cell
      cycle checkpoint-related rad1 gene and the mRNAs of differentially expressed
      genes by suppression subtractive hybridization (SSH) were analysed in the liver,
      and related to well-established biomarkers: cyp1A1 mRNA expression and assessment
      of the DNA integrity using the comet assay and flow cytometry. DMBA exposure
      resulted in increased cyp1A1 mRNA levels, suggesting that cyp1A1 might be
      involved in the metabolism of DMBA. Global DNA damage, detected by the comet
      assay, was observed in the three tissues analysed but only blood cells showed
      chromosomal lesions as analysed by flow cytometry. Although DNA damage was found
      in the liver, no induction in rad1 gene was observed in this organ. The global
      SSH approach revealed that mRNAs of genes related to xenobiotic metabolism,
      immune processes and cytoskeleton dynamics were differentially expressed in DMBA
      exposed eel livers, highlighting the complexity in the response observed in fish
      exposed to a genotoxic agent and providing directions for new biomarker
      development.

PMID- 19586670
TI  - Genotyping of Haemophilus parasuis from diseased pigs in China and prevalence of
      two coexisting virus pathogens.
AB  - From December 2003 to July 2006, a total of 131 (28.4%) Haemophilus parasuis
      strains were isolated from 462 cases examined in our diagnostic laboratory. These
      strains were isolated from clinically diseased pigs, and 50 of them along with 15
      reference strains of all known serovars were subjected to PCR-FRLP (restriction
      fragment length polymorphism) analysis by tbpA gene. The analysis of the 1.9-kb
      tbpA amplicon using TaqI, AvaI and RsaI endonucleases produced 9 RFLP patterns
      for the 15 reference strains and 13 patterns for the 50 field isolates. And the
      first three prevalent genotypes in China were DBN (38%), ABN (18%) and DBP (12%).
      Meanwhile, co-infection of H. parasuis, PRRSV and PCV2 was examined in the 462
      pig herds. It is indicated that 11.5% cases (53), 27.9% cases (129) and 4.8%
      cases (22) were infected only by H. parasuis, PRRSV and PCV2, respectively; and
      19.2% cases (89) and 3.0% cases (14) were co-infected with two or all of the
      three pathogens, respectively; the rest 33.6% cases (155) were not infected by
      any of the three pathogens. It is confirmed that H. parasuis existed widely in
      southeast China with numerous genotypes.

PMID- 19586671
TI  - Effects of immigration on the health insurance status of natives.
AB  - The objective of the paper is to estimate the effects of immigration on natives'
      probability of having private coverage and being uninsured. To examine whether
      immigrants affected employers' decisions to offer health benefits the study
      estimates immigration effects on natives' probability of being offered, eligible
      for, and a policy-holder of health insurance. Although in many cases the effects
      are statistically significant, most effects are very small. The increase in
      immigrant labor supply from 1995 to 2005 increases natives' uninsurance rates by
      about 0.7 percentage points and reduces the natives' probability of being offered
      and a holder of coverage by 0.8 and 1.9 percentage points, respectively.
      Immigrants' weaker preferences for coverage relative to natives' may be the key
      factor in this result.

PMID- 19586672
TI  - Survival after radiotherapy in gastric cancer: systematic review and meta
      analysis.
AB  - BACKGROUND AND PURPOSE: A systematic review and meta-analysis was performed to
      assess the impact of radiotherapy on both 3- and 5-year survival in patients with
      resectable gastric cancer. METHODS: Randomized Clinical Trials (RCTs) in which
      radiotherapy, (preoperative, postoperative and/or intraoperative), was compared
      with surgery alone or surgery plus chemotherapy in resectable gastric cancer were
      identified by searching web-based databases and supplemented by manual
      examination of reference lists. Meta-analysis was performed using Risk Ratios
      (RRs). Random or fixed effects models were used to combine data. The
      methodological quality was evaluated by Chalmers' score. RESULTS: Radiotherapy
      had a significant impact on 5-year survival. Using an intent to treat (ITT) and a
      Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48;
      NNT=17) and 1.31 (95% CI: 1.04-1.66; NNT=13), respectively. Although the quality
      of the studies was variable, the data were consistent and no clear publication
      bias was found. CONCLUSION: This meta-analysis showed a statistically significant
      5-year survival benefit with the addition of radiotherapy in patients with
      resectable gastric cancer. Radiotherapy remains a standard component in the
      treatment of resectable gastric cancer and new RCTs need to address the impact of
      new conformal radiotherapy technologies.

PMID- 19586673
TI  - DVH parameters and outcome for patients with early-stage cervical cancer treated
      with preoperative MRI-based low dose rate brachytherapy followed by surgery.
AB  - BACKGROUND: To our knowledge no DVH data have so far been reported for MRI-guided
      BT in the preoperative setting of early-stage cervical cancer. We assessed DVH
      parameters and clinical outcome using 3D MRI-guided preoperative intracavitary
      LDR BT. PATIENTS AND METHODS: Thirty-nine patients with primary early cervical
      carcinoma (IB1 37, IIA 1 and IIB 1) were treated with preoperative MRI-based LDR
      BT, consisting of uterovaginal BT to a total dose of 60 Gy to the intermediate
      risk CTV, followed 6 weeks later by bilateral salpingo-oophorectomy and
      extrafascial hysterectomy plus pelvic node dissection. Adjuvant chemoradiation
      was delivered to patients with pelvic lymph node involvement. RESULTS: With a
      median follow-up of 4.4 years (range 2.6-6.6 years), local recurrence occurred in
      1 patient (a lateropelvic relapse) (2.6%). The 4-year actuarial overall survival
      and disease-free survival were 94% (95% CI, 82-98), and 86% (95% CI, 67-95),
      respectively. The 2- and 4-year actuarial local relapse-free survival were 94
      (95% CI, 86-100) and 91% (95% CI, 81-100), respectively. For intermediate-risk
      CTV, median D(100) and D(90) were 43 Gy(alpha)(/)(beta)(10) (range 2-74
      Gy(alpha)(/)(beta)(10)) and 75 Gy(alpha/beta)(10), respectively (range 29-129
      Gy(alpha/beta)(10)). For high-risk CTV, the median D(100) and D(90) were 69
      Gy(alpha/beta)(10) (range 24-137 Gy(alpha/beta)(10)) and 109 Gy(alpha/beta)(10)
      (range 37-198 Gy(alpha/beta)(10)), respectively. Twenty grade 1-2 late
      complications were observed in 13 patients (33.3%): 10 bladder, 3 ureteral, 1
      rectal, 1 small bowel, 1 vaginal, 1 pelvic fibrosis, 1 peripheral nerve, and 2
      others. No grade 3 or 4 complication occurred. CONCLUSION: MRI-guided
      brachytherapy with adaptation of the time duration and/or the length of each
      radioactive source allows both high local control and low toxicity in the
      preoperative settings of early-stage cervical cancers.

PMID- 19586674
TI  - Ultrasonographic and thermographic screening for latent inflammation in diabetic
      foot callus.
AB  - AIMS: Inflammation within the diabetic foot callus may be an earliest, predicting
      symptom of foot ulcer developing later. The purpose of this study was to identify
      latent inflammation within the foot callus using thermography and
      ultrasonography, and to investigate relationship between the inflammatory
      findings in callus and presence or absence of diabetes. METHODS: This was a cross
      sectional study of 60 cases with asymptomatic foot callus; the 30 diabetic
      patients and the 30 non-diabetic matched volunteers. Inflammation was defined
      using physiological imaging techniques; as skin temperature elevation in
      thermography and low echoic lesion in ultrasonography. RESULTS: Sixty-three and
      ninety-four calli were observed in the diabetic and non-diabetic groups,
      respectively. The inflammation signs were detected by both of the two techniques
      in 10% of the calli in the diabetic group. No inflammation was noted in the non
      diabetic group (p=0.014). CONCLUSIONS: The inflammation signs presented here were
      specifically observed in the diabetic group. We consider that the physiological
      imaging techniques may be valuable screening tools for potential risk of diabetic
      foot ulcers.

PMID- 19586677
TI  - Tumor-derived molecular information and outcome in hepatocellular carcinoma.

PMID- 19586678
TI  - A new French paradox: HBV vaccination.

PMID- 19586676
TI  - Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in
      Caucasians with chronic hepatitis C infection.
AB  - BACKGROUND/AIMS: Seven genomic loci, implicated by single nucleotide
      polymorphisms (SNPs), have recently been associated with progression to advanced
      fibrosis (fibrosis risk) in patients with chronic hepatitis C virus. Other
      variants in these loci have not been examined but may be associated with fibrosis
      risk independently of or due to linkage disequilibrium with the original
      polymorphisms. METHODS: We carried out dense genotyping and association testing
      of additional SNPs in each of the 7 regions in Caucasian case control samples.
      RESULTS: We identified several SNPs in the toll-like receptor 4 (TLR4) and
      syntaxin binding protein 5-like (STXBP5L) loci that were associated with fibrosis
      risk independently of the original significant SNPs. Haplotypes consisting of
      these SNPs in TLR4 and STXBP5L were strongly associated with fibrosis risk
      (global P=3.04 x 10(-5) and 4.49 x 10(-6), respectively). CONCLUSIONS: Multiple
      variants in TLR4 and STXBP5L genes modulate risk of liver fibrosis. These
      findings are of relevance for understanding the pathogenesis of HCV-induced liver
      disease in Caucasians and may be extended to other ethnicities as well.

PMID- 19586680
TI  - A framework for analysing migrant health policies in Europe.
AB  - Evidence suggests migrants experience inequalities in health and access to health
      care. However, to date there has been little analysis of the policies employed to
      address these inequalities. This article develops a framework to compare migrant
      health policies, focusing on England, Italy, the Netherlands and Sweden. The
      first issue addressed in the framework is data collection. All four countries
      collect migrant health data, but many methodological limitations remain. The
      second issue is targeting of population groups. Countries typically focus either
      on first generation immigrants or on ethnic minorities, but not both, despite the
      often divergent needs of the two groups. Another issue is whether specific
      diseases should take priority in migrant health policy. While communicable
      diseases, sexual and reproductive health and mental health have been targeted,
      there may be a lack of attention paid to lifestyle related risk factors and
      preventive care. Fourthly, decisions about the mix of demand and supply-side
      interventions need to be made and evaluated. Finally, the challenge of
      implementation is discussed. Although migrant health policy has been elaborated
      in the four countries, implementation has not necessarily reflected this on the
      ground. These experiences signal important policy issues and options in the
      development of migrant health policies in Europe.

PMID- 19586679
TI  - Prevalence, viral replication efficiency and antiviral drug susceptibility of
      rtQ215 polymerase mutations within the hepatitis B virus genome.
AB  - BACKGROUND/AIMS: The rtQ215S mutation in the hepatitis B virus (HBV) polymerase
      has been described as a secondary mutation associated with resistance to
      lamivudine (LAM) and adefovir (ADV). We aimed at assessing the prevalence of
      substitutions at rtQ215 of the HBV polymerase and determining the molecular and
      functional consequences using phenotypic analyses in vitro. METHODS: The
      polymerase region was directly sequenced in HBV isolates from a cohort of 249 HBV
      genotype D-infected patients from Iran (174 males/75 females, 194 treatment-nai
      ve/ 55 LAM-treated). Replication-competent HBV constructs containing the
      naturally occurring rtQ215H, rtQ215P and rtQ215S mutations were generated, and
      compared to wild-type, LAM- (rtM204I, rtL180M/rtM204V) and ADV-resistant
      (rtN236T) clones. RESULTS: In an Iranian cohort of 249 HBV infected patients,
      14.5% (36/249) showed mutations in the rtQ215 locus, namely 6.8% rtQ215S, 3.6%
      rtQ215P and 4.1% rtQ215H. The frequency of rtQ215 substitutions was higher in LAM
      treated than treatment-nai ve patients (25% vs. 11%), but not associated with
      clinical complications. In phenotypic assays, rtQ215S, rtQ215P and rtQ215H
      constructs showed equivalent levels of viral replication as wild-type HBV,
      whereas LAM- and ADV-resistant mutants had significantly impaired replicative
      capacities. Furthermore, rtQ215S, rtQ215P and rtQ215H harbouring constructs
      remained susceptible towards treatment with LAM or ADV in vitro. CONCLUSIONS: Our
      study reveals that rtQ215 substitutions in the HBV polymerase frequently occur in
      chronic hepatitis B, even without exogenous selection pressures. As these
      substitutions do neither impair the viral replication efficiency nor
      susceptibility to LAM or ADV in vitro, rtQ215 substitutions likely represent
      background polymorphisms rather than resistance mutations with clinical
      implications.

PMID- 19586682
TI  - A new dawn for citizen science.
AB  - A citizen scientist is a volunteer who collects and/or processes data as part of
      a scientific enquiry. Projects that involve citizen scientists are burgeoning,
      particularly in ecology and the environmental sciences, although the roots of
      citizen science go back to the very beginnings of modern science itself.

PMID- 19586681
TI  - Relationships between lung adenocarcinoma and gender, age, smoking and
      occupational risk factors: A case-case study.
AB  - BACKGROUND: The hypothesis that some risk factors for lung cancer may have more
      specific associations with particular histologic types remains controversial. The
      aim of this study was to investigate possible associations between adenocarcinoma
      and gender, age, smoking characteristics and selected occupational carcinogens in
      relation to other histologic types. METHODS: This study included all
      histologically confirmed lung cancer cases diagnosed consecutively in two French
      University hospitals from 1997 to 2006. All medical data were obtained by face-to
      face patient interviews. Occupational carcinogen exposures of each patient were
      assessed by an industrial hygienist. Relationships between risk factors and
      adenocarcinoma were analyzed by case-case comparisons using unconditional
      logistic regressions (ULRs). RESULTS: A total of 1493 subjects were enrolled in
      this study, comprising 1303 men (87.3%), 67 nonsmokers (4.5%) and 489
      adenocarcinomas (32.7%). Using ULR, no associations were observed between
      adenocarcinoma and age, gender or smoking characteristics except for a negative
      relationship with smoking duration (p<0.0001). Significant associations were
      observed between ADC and exposure to welding fumes and silica in the whole
      population and with polycyclic aromatic hydrocarbons in ever smokers. CONCLUSION:
      This study demonstrated that some risk factors, such as duration of smoking and
      certain occupational exposures but not gender or age, have a more important
      influence on the incidence of lung ADC than on other histologic types. As the
      distribution of histologic types may reflect underlying biological mechanisms,
      these findings also suggest that lung carcinogenesis pathways should be studied
      in relation to smoking duration and other lung cancer risk factors.

PMID- 19586683
TI  - HSV-1 upregulates the ARE-binding protein tristetraprolin in a STAT1- and p38
      dependent manner in mature dendritic cells.
AB  - Dendritic cells are the sentinels of the immune system and as such represent the
      first-line of defense against incoming pathogens. Upon encounter with harmful
      antigens, these antigen-presenting cells start to mature and migrate towards the
      draining lymph nodes to display the antigen to T-lymphocytes, thereby eliciting
      the immune response of the host. Viruses, including human herpesvirus type I (HSV
      1), seek to avoid such immune reactions. Therefore, they developed an arsenal of
      immune evasion strategies, some of which have been described earlier by our group
      and others. The secretion of tumor necrosis factor (TNF) represents a typical
      defense line of the host and it has been shown that this cytokine contributes to
      the inhibition of viral replication and augments the proliferation of cytotoxic T
      lymphocytes. Here we report, that upon infection of mature dendritic cells, HSV-1
      very strongly induces the expression of the AU-rich elements (ARE)-binding
      protein tristetraprolin (TTP), an mRNA-destabilizing protein. One of the best
      described targets of TTP is the TNF mRNA. This induction is dependent on the
      phosphorylation of both signal transducer and activator of transcription (STAT1)
      and p38 in a collaborative manner. By repressing this phosphorylation with
      specific inhibitors, we were able to reduce TTP mRNA levels. At the same time TNF
      mRNA levels were increased, suggesting that TNF mRNA is indeed a target of TTP in
      this setting. In summary, these data underline that HSV-1 induces TTP
      transcription in order to reduce TNF levels generated by infected mature
      dendritic cell.

PMID- 19586684
TI  - Specific inhibition of the classical complement pathway with an engineered single
      chain Fv to C1q globular heads decreases complement activation by apoptotic
      cells.
AB  - Apoptotic cells are potent complement activators; and proposed mechanisms include
      IgM-mediated classical pathway activation, C-reactive protein (CRP)-mediated
      classical pathway activation, and IgM-mediated lectin pathway activation. While
      complement activation is beneficial in clearing apoptotic cells, the resulting
      complement-mediated inflammation may extend damage to the surrounding cells and
      tissues, as observed in ischemia/reperfusion injury. We previously engineered and
      characterized a single-chain Fv against C1q globular heads (scFv(QuVHVL)) that
      blocked C1q binding to immobilized IgG and to IgG-sensitized cells, and thereby
      inhibited IgG-mediated classical pathway activation [Hwang H.Y., Duvall M.R.,
      Tomlinson S., Boackle R.J., 2008. Highly specific inhibition of C1q globular-head
      binding to human IgG: a novel approach to control and regulate the classical
      complement pathway using an engineered single-chain antibody variable fragment.
      Molecular Immunology 45, 2570-2580]. In the present study, this scFv(QuVHVL) was
      examined for its ability to restrict complement deposition on apoptotic cells in
      the presence of fresh normal human serum (NHS). Interestingly, the addition of
      scFv(QuVHVL) to NHS decreased C1-mediated C4b deposition on apoptotic cells by
      60% as compared to appropriate buffer-treated control serum. By inhibiting
      initiation of the early complement components, the subsequent C3b and membrane
      attack complex depositions were inhibited by 70%. Apoptotic cells may acquire
      serum CRP, a known classical complement pathway activator. It was observed that
      scFv(QuVHVL) blocked C1 binding to CRP and blocked CRP-mediated classical pathway
      activation using an ELISA format. However, under the experimental conditions
      used, the addition of exogenous CRP to apoptotic cells did not further increase
      the levels of C4b, C3b, or MAC deposition significantly, suggesting predominance
      by other activation mechanisms, such as antibody-C1-mediated complement
      activation. In summary, the results indicated that C1-mediated classical pathway
      activation was a highly significant mechanism for complement activation by
      apoptotic cells. In the future, specific inhibition of classical complement
      pathway activation by a humanized form of scFv(QuVHVL) may be useful in reducing
      inadvertent damage to healthy bystander tissue in a variety of acute, complement
      mediated inflammatory conditions, including ischemia/reperfusion injury.

PMID- 19586685
TI  - Diversity and plasticity of the innate immune response. Preface.

PMID- 19586686
TI  - Prediction of volume of distribution values in human using immobilized artificial
      membrane partitioning coefficients, the fraction of compound ionized and plasma
      protein binding data.
AB  - We developed an improved Lombardeo's method (J. Med. Chem., 2004) for prediction
      of VD(ss) in human. With ElogD substituted by logk(IAM), together with f(i (7.4))
      (the fraction of compound ionized at pH 7.4) and logf(u) (logarithmic fraction of
      compound unbound in plasma), the predictive equation of f(ut) (the fraction of
      the compound unbound in tissues) for the 121 compounds was built, predictive
      VD(ss) was further obtained from the Oie-Tozer equation. Our model could be
      applicable to structurally diverse compounds, including acids, bases, neutrals,
      and ampholytes. Interior and exterior validation results indicated the model had
      a robust predictive ability. Compared to the Lombardeo's and Hollosy's (J. Med.
      Chem., 2006) methods, our model can be generally applicable with better
      predictive accuracy.

PMID- 19586687
TI  - Search for new pharmacophores for antimalarial activity. Part III: synthesis and
      bioevaluation of new 6-thioureido-4-anilinoquinazolines.
AB  - Syntheses and in vitro antimalarial evaluation of 42 new thioureidoquinazolines
      have been carried out. Several analogs showed promising antimalarial effect in
      the in vitro investigation against chloroquine-sensitive 3D7 strain of Plasmodium
      falciparum whereas one of the compounds shows 50% curative effect in the mouse
      model at an oral dose of 100mg/kg x 4 days against multidrug resistant Plasmodium
      yoelii nigeriensis.

PMID- 19586688
TI  - Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine
      derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial
      agents.
AB  - The reaction of 5,6-diphenyl-3-hydrazino-1,2,4-triazine (1) with
      bis(methylthio)methylene]malononitrile (2) afforded 5-amino-1-(5,6-diphenyl-1,2,4
      triazin-3-yl)-3-(methylthio)-1H-pyrazole-4-carbonitrile (3). Compound 3 reacted
      with thiourea to give 3,4-diaminopyrazolo[3,4-d]pyrimidine 5, which was treated
      with benzoyl chloride to give pyrazolo[5,4,3-kl]pyrimido[4,3-d]pyrimidine 6.
      Treatment of 3 with acetic anhydride produced 3-methylthio-pyrazolo[3,4
      d]pyrimidine derivative 7, which was allowed to react with hydrazine hydrate to
      give the corresponding hydrazino derivative 8. Heterocyclization of 8 with
      benzoyl chloride and sodium pyruvate afforded the polyfused heterocycles 9 and
      10, respectively. Reaction of 3 with benzoylacetone yielded pyrazolo[3,4
      b]pyridine 12, which was allowed to react with malononitrile and acetanilide to
      get heterocyclic systems 13 and 14, respectively. Interaction of 3 with
      cyanoacetone gave pyrazolo[3,4-b]pyridine 15, which was refluxed in formic acid
      to yield pyrazolo[4',3':5,6]pyrido[4,3-d]pyrimidine 16. Reaction of 3 with 2
      afforded the triazinylpyrazole derivative 17, which was reacted with hydrazine
      hydrate to give dipyrazolo[1,5-a:3',4'-d]pyrimidine 19. Furthermore, treatment of
      the latter compound with methyl anthranilate furnished tetraheterocyclic compound
      21. Structures of the products have been determined by elemental analysis and
      spectral studies. All compounds have been screened for their antibacterial and
      antifungal activities. Compounds 9, 10, 13, 19 and 21 showed maximum activity
      comparable to the standard drugs with lower toxicity in the case of 9 and 10.

PMID- 19586689
TI  - 3D QSAR study of the toxicity of trichothecene mycotoxins.
AB  - Trichothecene mycotoxins, toxic natural products of fungi from the family
      Hypocreaceae, are potent inhibitors of protein synthesis. The application of 3D
      QSAR to these toxins explored the structural basis for their biological
      activities. A CoMFA (Q(2)=0.619, R(2)=0.921) model was developed for a set of 15
      toxins with the trichothecene nucleus; CoMFA (Q(2)=0.518, R(2)=0.855) and CoMSIA
      (Q(2)=0.695, R(2)=0.960) models were developed for 31 toxins with the nucleus and
      a macrolide ring. The results show the role of electrostatics and steric factors
      in the activity of the toxins and indicate that the conformation of the macrolide
      ring influences the toxicity of the macrolide toxins.

PMID- 19586690
TI  - [Cough syncope caused by a possible Chlamydia pneumoniae pneumonia].
AB  - We report the case of a 61-year-old man who presented with coughing fits followed
      by sinus pauses and syncope. Cardiac and neurological diagnostic work-up was
      negative and the patient was considered to have cough syncope. As this occurred
      within the context of febrile pneumonia, an infectious disease was suspected but
      diagnostic work-up only revealed an increase of antibodies against Chlamydia
      pneumoniae. The responsibility of this agent is discussed. Clinical recovery was
      obtained with the prescription of antitussive medication.

PMID- 19586691
TI  - A cross-sectional study of emotional intelligence in baccalaureate nursing
      students.
AB  - Emotional intelligence (EI) has been identified as a set of competencies
      necessary for workplace success. EI is deemed essential for effective nursing
      practice, yet little research has been done in nursing. The purpose of this study
      was to describe the EI scores of baccalaureate nursing students and to determine
      if there was a difference among the students across the four years of the
      program. A cross-sectional design was used to examine the EI scores of 100 female
      nursing students (25 in each of the four years). Students completed the BarOn
      Emotional Quotient Inventory Short (EQ-i:S), a 51-item self-report questionnaire
      that includes scores for a total EQ and 5 subscales. Undergraduate nursing
      students in each of the four years of the program had EI scores within the
      emotionally and socially effective functioning capacity, identifying them as
      being able to establish satisfying interpersonal relationships, and work well
      under pressure. The difference in total EQ scores between students in Year 1 and
      Year 4 was statistically significant (p= or <.05) as were the scores in the
      interpersonal and the stress management subscales (p= or <.05) with students in
      Year 4 scoring higher than those in Year 1. Implications for nursing education
      are discussed.

PMID- 19586692
TI  - Spatial distribution of uranium and thorium in the surface soil around proposed
      uranium mining site at Lambapur and its vertical profile in the Nagarjuna Sagar
      Dam.
AB  - The understanding and evaluation of the possible interactions of various
      naturally occurring radionuclides in the world's third largest man-made dam,
      Nagarjuna Sagar located in Andhra Pradesh, India and built on river Krishna
      assumed significance with the finding of uranium deposits in locations near the
      dam. For the present work, surface soil samples from the mineralized area of
      Lambapur, Mallapuram, Peddagattu and sediment core samples from the Nagarjuna
      Sagar dam were analyzed for naturally occurring radionuclides namely uranium and
      thorium using gamma spectrometric technique. Also toxic elements lead and
      chromium were analysed by the Energy Dispersive X-ray Fluorescence Spectrometer
      (EDXRF) technique. Surface soil samples show a variation from 25 to 291 Bq/kg
      (2.02-23.5 mg/kg) for (238)U and 32-311 Bq/kg (7.9-76.9 mg/kg) for (232)Th. U/Th
      concentration ratio in surface soil samples ranged from 0.19 to 0.31 and was
      found comparable with the nation wise average of 0.26. The study of sediment core
      samples reflected higher U/Th concentration ratio of 0.30-0.33 in the bottom
      section of the core as compared to 0.22-0.25 in the upper section. The
      concentration ratio in the upper section of the core was similar to the ratio
      0.23 found in the western Deccan Basalt region through which the river
      originates. A higher concentration of lead and chromium was observed in the upper
      section of the core compared to bottom section indicating the impact of river
      input on the geochemical character of dam sediment.

PMID- 19586693
TI  - Inventories of 239+240Pu, 137Cs, and excess 210Pb in sediments from freshwater
      and brackish lakes in Rokkasho, Japan, adjacent to a spent nuclear fuel
      reprocessing plant.
AB  - We investigated the vertical profiles of (239+240)Pu, (137)Cs, and excess (210)Pb
      ((210)Pb(ex)) in sediment core samples obtained from two freshwater lakes and two
      brackish lakes situated near the first commercial spent nuclear fuel reprocessing
      plant in Rokkasho, Japan, before the final test of the plant using actual spent
      nuclear fuel. The inventory of (239+240)Pu in those lakes was larger than that in
      soil in Rokkasho, which indicated the inflow of (239+240)Pu from the catchment
      area in addition to direct deposition on the lake surfaces. The (137)Cs inventory
      in sediments of the brackish lakes was lower than that in the soil, which showed
      that part of the (137)Cs was removed from the sediments by the brackish water or
      that it was not deposited into the sediments, because of the high solubility of
      Cs in brackish water. The (137)Cs inventory in sediments of the freshwater lakes
      was higher than that of the brackish lakes, and comparable with that in soil
      except for one core sample out of four. The (239+240)Pu/(137)Cs ratio in
      freshwater lake sediments was higher than that in soil, and that indicated that
      part of the (137)Cs was lost from the sediments. The low inventory of (137)Cs may
      be attributable to competition for absorption sites in sediments with ammonium
      ions formed in the reducing environment which occurs from summer to fall in the
      sediments. Those data will be used as background data on the artificial
      radionuclides in the lakes to assess the effect of released radionuclides on
      their concentrations.

PMID- 19586694
TI  - A retrospective study in management of carotid body tumour.
AB  - We report our experience of the management of 53 patients with 57 carotid body
      tumours from two units of oral and maxillofacial surgery in China between 1995
      and 2006. Digital subtraction angiography was used most often for the
      confirmation of diagnosis and preoperative assessment. Fifty-one patients with 55
      tumours had their tumours resected and 2 patients had radiotherapy. Of the 55
      excised tumours, 14 were resected successfully without injury to the carotid
      artery, 25 were resected with the external carotid artery, 5 had arteriorrhaphy,
      and 11 resulted in sacrificing the unilateral internal carotid artery (ICA). Six
      patients had interposition reconstruction of the ICA. Immediately after operation
      14 patients (27%) had neurological damage, which was permanent in 3 (6%), and 2
      (4%) developed stroke. There were no deaths. Once the ICA is resected, vascular
      reconstruction is recommended to minimise neurological morbidity.

PMID- 19586695
TI  - Relation between the concentration of zinc in maternal whole blood and the risk
      of an infant being born with an orofacial cleft.
AB  - We investigated the relation between concentrations of maternal zinc and copper
      and the risk of an infant being born with an orofacial cleft. We did a case
      control study using 116 mothers of children with isolated cleft lip with or
      without cleft palate (cleft group), and 64 mothers of unaffected children
      (control group). Mothers with a whole blood zinc concentration of 47.1 micromol/L
      or less had a risk 2.5 times higher of having a child with an orofacial cleft
      than those with a higher concentration (or level) (95% CI 1.03-6.23; p<0.05). A
      low zinc concentration combined with a high copper concentration was seen only in
      the cleft group. This evidence suggests an association between concentrations of
      maternal zinc and the risk of orofacial clefts in offspring.

PMID- 19586697
TI  - Detecting atmospheric pollution in surface soils using magnetic measurements: a
      reappraisal using an England and Wales database.
AB  - Industrial activity such as burning of fossil fuels produces magnetically
      enhanced particulates. These particulates consist of coarse-grained multidomain
      and stable single domain magnetic minerals. Two threshold values of low field
      magnetic susceptibility (chi(LF)) and frequency dependent susceptibility
      percentage (chi(FD)%) discriminate ferrimagnetic minerals of these sizes and can
      act as a tracer of magnetic pollution. Application of the thresholds to a
      magnetic topsoil data set (n=5656 across England and Wales) revealed 637 samples
      potentially dominated by pollution particulates. The magnetic parameters of these
      samples display a negative correlation with distance to urban areas and positive
      correlations with metals associated with anthropogenic activity (Cu, Pb, and Zn).
      Results of experimentation with threshold values and modelling of magnetic
      anomalies suggest that regional factors such as geology and potential for
      pedogenic secondary magnetic enhancement should be considered when setting
      threshold values.

PMID- 19586696
TI  - The validation and translation of Multidimensional Measure of Informed Choice in
      Greek.
AB  - OBJECTIVE: to translate the original English version of the Multidimensional
      Measure of Informed Choice (MMIC) into Greek, to adapt it culturally to Greece,
      and to determine its psychometric properties for the assessment of informed
      choice in antenatal screening for Down syndrome. DESIGN: survey using self
      administrated questionnaires. SETTING: public hospital in Athens, Greece.
      PARTICIPANTS: 135 pregnant women with gestational age between 11th and 20th week
      just prior to having antenatal screening for Down syndrome. FINDINGS: 96% of
      women had a positive attitude towards screening and 45% had a good level of
      knowledge concerning the screening process for Down syndrome. Using a standard
      measure of informed choice, validated for use in Greek, it was found that 44% of
      women made an informed choice, and thus 56% of women made an uninformed choice.
      The internal consistency of the scales was good; Cronbach's alpha was found to be
      0.76 for the attitude scale and 0.64 for the knowledge scale, suggesting that all
      items were appropriate to measure. The performed factor analysis of the attitude
      scale indicated three factors with an eigenvalue over 1.0. Those factors were
      responsible for 87% of the variance. KEY CONCLUSIONS: this study indicates that
      the Greek version of the MMIC appears to be a reliable and valid tool for
      measuring informed choice in antenatal screening for Down syndrome. Due to its
      short length and consumption of time, it seems to be a practical instrument for
      use in Greek antenatal clinics.

PMID- 19586698
TI  - Spatial patterns and autocorrelation in the response of microarthropods to soil
      pollutants: the example of oribatid mites in an abandoned mining and smelting
      area.
AB  - Although exogenous factors such as pollutants can act on endogenous drivers (e.g.
      dispersion) of populations and create spatially autocorrelated distributions,
      most statistical techniques assume independence of error terms. As there are no
      studies on metal soil pollutants and microarthropods that explicitly analyse this
      key issue, we completed a field study of the correlation between Oribatida and
      metal concentrations in litter, organic matter and soil in an attempt to account
      for spatial patterns of both metals and mites. The 50-m wide study area had
      homogenous macroscopic features, steep Pb and Cu gradients and high levels of Zn
      and Cd. Spatial models failed to detect metal-oribatid relationships because the
      observed latitudinal and longitudinal gradients in oribatid assemblages were
      independent of the collinear gradients in the concentration of metals. It is
      therefore hypothesised that other spatially variable factors (e.g. fungi, reduced
      macrofauna) affect oribatid assemblages, which may be influenced by metals only
      indirectly.

PMID- 19586699
TI  - Couples, PMTCT programs and infant feeding decision-making in Ivory Coast.
AB  - In Sub-Saharan Africa, prevention of HIV pediatric infection due to breastfeeding
      requires turning to alternatives to prolonged breastfeeding: artificial feeding
      or exclusive breastfeeding with early weaning. Choosing a preventive option and
      applying it does not only depend upon the mother but also on the father and more
      specifically on couple interactions. To date, not enough studies have considered
      this question. In Abidjan, Ivory Coast, HIV-positive women and their infants were
      followed over two years in Ditrame Plus, a prevention of mother-to-child
      transmission (PMTCT) project. Using data from this project and from interviews
      conducted with couples and women, we analyzed the construction of decisions and
      practices concerning the application of preventive infant feeding options.
      Differences may be found between women and men in discourses regarding their
      attitudes, which are in part related to their conceptions of motherhood and
      fatherhood. We found that when men know their wife is HIV positive and are
      involved in the PMTCT project, they play an active role in applying the advice
      received. However, women do not always need the support of their spouse to
      undertake preventative behaviour. The project team also plays an important role
      in the adoption of such by women and men. The implementation of preventive
      options is a complex process in which three groups of actors (women, men and the
      project team) interact. In order to optimize PMTCT programs for couples, it is
      essential that this dynamic be taken into account.

PMID- 19586701
TI  - Comparison of two mechanical intraosseous infusion devices: a pilot, randomized
      crossover trial.
AB  - INTRODUCTION: Administration of medications via the intraosseous (IO) route has
      proven to be a lifesaving procedure in critically ill or injured children. Two
      mechanical IO infusion devices have been approved for use in children, the spring
      loaded IO infusion device (Bone Injection Gun, BIG) and the battery-powered IO
      infusion drill (EZ-IO). The objective of this pilot study was to compare the
      success rates for insertion and the ease-of-use of the two devices. PATIENTS AND
      METHODS: A randomized crossover study was conducted in a local paramedic training
      course with 29 paramedic students participating. Participants watched two videos
      describing the use of the two devices, followed by a demonstration on how to use
      each device on a turkey bone model. Then subjects were divided into two study
      groups: BIG-first or EZ-IO-first. Each participant performed one insertion
      attempt with each device independently. All attempts were filmed by a video
      camera. Successful placement was defined as the visualization of fluid flow from
      the marrow cavity. Following the study procedure, participants completed a two
      item questionnaire recording their ranking of the ease-of-use of each device and
      their "first choice device". RESULTS: Participants had a significantly higher one
      attempt success rate with the EZ-IO than with the BIG (28/29 vs 19/29, p=0.016),
      and selected the EZ-IO as their first choice (20/29). Participants of the EZ-IO
      first group assessed the EZ-IO as easier to use than the BIG (p=0.0039). The
      subjects of the BIG-first group found no difference in the ease-of-use between
      the two devices (p=0.32). CONCLUSIONS: As tested by paramedic students on a
      turkey bone model, the EZ-IO demonstrated higher success rates than the BIG and
      was the preferred device. Future studies are planned to determine which of the
      two devices is more appropriate for obtaining IO access in the setting of
      paediatric emergencies.

PMID- 19586700
TI  - Neural correlates of metaphor processing: the roles of figurativeness,
      familiarity and difficulty.
AB  - There is currently much interest in investigating the neural substrates of
      metaphor processing. In particular, it has been suggested that the right
      hemisphere plays a special role in the comprehension of figurative (non-literal)
      language, and in particular metaphors. However, some studies find no evidence of
      right hemisphere involvement in metaphor comprehension (e.g. [Lee, S. S., &
      Dapretto, M. (2006). Metaphorical vs. literal word meanings: fMRI evidence
      against a selective role of the right hemisphere. NeuroImage, 29, 536-544; Rapp,
      A. M., Leube, D. T., Erb, M., Grodd, W., & Kircher, T. T. J. (2004). Neural
      correlates of metaphor processing. Cognitive Brain Research, 20, 395-402]). We
      suggest that lateralization differences between literal and metaphorical language
      may be due to factors such as differences in familiarity ([Schmidt, G. L.,
      DeBuse, C. J., & Seger, C. A. (2007). Right hemisphere metaphor processing?
      Characterizing the lateralization of semantic processes. Brain and Language, 100,
      127-141]), or difficulty ([Bookheimer, S. (2002). Functional MRI of language: New
      approaches to understanding the cortical organization of semantic processing.
      Annual Review of Neuroscience, 25, 151-188; Rapp, A. M., Leube, D. T., Erb, M.,
      Grodd, W., & Kircher, T. T. J. (2004). Neural correlates of metaphor processing.
      Cognitive Brain Research, 20, 395-402]) in addition to figurativeness. The
      purpose of this study was to separate the effects of figurativeness, familiarity,
      and difficulty on the recruitment of neural systems involved in language, in
      particular right hemisphere mechanisms. This was achieved by comparing neural
      activation using functional magnetic resonance imaging (fMRI) between four
      conditions: literal sentences, familiar and easy to understand metaphors,
      unfamiliar and easy to understand metaphors, and unfamiliar and difficult to
      understand metaphors. Metaphors recruited the right insula, left temporal pole
      and right inferior frontal gyrus in comparison with literal sentences. Familiar
      metaphors recruited the right middle frontal gyrus when contrasted with
      unfamiliar metaphors. Easy metaphors showed higher activation in the left middle
      frontal gyrus as compared to difficult metaphors, while difficult metaphors
      showed selective activation in the left inferior frontal gyrus as compared to
      easy metaphors. We conclude that the right hemisphere is involved in metaphor
      processing and that the factors of figurativeness, familiarity and difficulty are
      important in determining neural recruitment of semantic processing.

PMID- 19586702
TI  - Improving the effectiveness of bystander cardiopulmonary resuscitation (CPR) by
      redefining the two-stage method of teaching laypersons.

PMID- 19586704
TI  - Exploding masks--universal connectors in emergency airway equipment.

PMID- 19586703
TI  - Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after
      successful resuscitation from out-of-hospital cardiac arrest.
AB  - To investigate the incidence of iatrogenic dyscarbia in survivors of out-of
      hospital cardiac arrest treated with induced mild hypothermia.We performed a
      retrospective cohort study of the ventilatory management based on blood gas
      analyses of patients resuscitated from prehospital cardiac arrest. In the pilot
      phase, we assessed the ventilatory management in the patients treated in one
      university hospital during a 4-year study period. Subsequently, a more recent (1
      year) retrospective cohort of resuscitated patients from all five Finnish
      university hospitals concerning the first 48h after hospital admission was
      analyzed. Core temperatures and temperature corrected (or non-corrected) blood
      gas analysis results with focus on carbon dioxide tension were analyzed. In
      addition, a survey was performed to investigate the ventilatory strategies in all
      Finnish hospitals providing mild hypothermia for cardiac arrest victims.The pilot
      cohort suggested a high incidence of hypo- or hyper-carbia during hypothermia
      treatment. In the multicenter patient population of 122 patients contributing a
      total of 1627 measurements, the PaCO(2) distribution was as follows: less than 4
      kPa in 148 samples out of 1627 (9%), 4-4.6 kPa in 404 (25%), 4.7-6 kPa in 887
      (55%) and more than 6 kPa in 188 samples (12%). There was a significant
      difference in the incidence of hypercarbia between the hospitals (p<0.05).We
      conclude that normocarbia was achieved/maintained only in approximately 55% of
      the samples. The incidence of hypo- or hyper-carbia (dyscarbia) was high (45%).
      This may predispose for serious derangements in the cerebral perfusion of the
      resuscitated patient. These results call for vigilance in adjustment of the
      ventilatory management to meet the needs of the patients treated with mild
      hypothermia.

PMID- 19586705
TI  - A national survey of prevalence of cardiopulmonary resuscitation training and
      knowledge of the emergency number in Ireland.
AB  - AIM: The aim of this survey was to establish prevalence of cardiopulmonary
      resuscitation (CPR) training within the last 5 years and reasons preventing
      training and initiation of CPR in Ireland as well as awareness of the emergency
      numbers. METHODS: An in-home omnibus survey was undertaken in 2008 with quota
      sampling reflecting the age, gender, social class and geography of Ireland.
      RESULTS: Of the 974 respondents, 23.5% had undergone CPR training in the previous
      5 years with lower social class and age 65 years and older significantly less
      likely to be trained. The workplace was both a major source of awareness as well
      as training for those trained. In the untrained group lack of awareness of the
      need for CPR training was the most significant reason for non-training. Cost was
      not cited as a barrier. 88.9% of people gave a correct emergency number with
      geographical variation. Notably, the European emergency number 112 was not well
      known. CONCLUSION: Previous Irish and American population targets for CPR
      training have been surpassed in Ireland in 2008. New internationally agreed
      targets are now required. Meanwhile older people and those in lower socio
      economic groups should be targeted for training. Awareness of at least one
      emergency number is very high in Ireland. Some geographical variation was found
      and this should be studied further.

PMID- 19586707
TI  - Surfactant therapy for acute respiratory failure after drowning: two children
      victim of cardiac arrest.

PMID- 19586708
TI  - Open-label study of ultra low-dose mifepristone for the treatment of uterine
      leiomyomata.
AB  - OBJECTIVE: To assess the effect of ultra low-dose mifepristone on uterine size,
      pain, bleeding and quality of life among women with symptomatic leiomyomata.
      STUDY DESIGN: Open-label cohort study of 2.5mg mifepristone orally among adult
      women with at least moderately severe symptoms related to leiomyomata and total
      uterine volume of greater than 160 cm(3), or at least one myoma of greater than
      2.5 cm diameter. Assessments of leiomyomata and uterine size (ultrasound), pain
      (McGill Pain Questionnaire), bleeding (daily log duration), quality of life
      (Uterine Fibroid Symptom and Quality of Life) and health status (SF-36) were
      conducted at baseline, three months and six months. Endometrial sampling was done
      at baseline and six months. RESULTS: Seventeen (74%) participants completed the
      entire six-month trial. Each of the measures showed significant improvement at
      six months compared to baseline (p<0.001). Uterine volume decreased by 11% and
      anemia, bleeding, pain, health status and fibroid-related quality of life
      improved during the course of the trial. Endometrial sampling showed cystic
      glandular dilatation, but no evidence of endometrial hyperplasia or cellular
      atypia. CONCLUSION: Treatment of women with symptomatic leiomyomata with ultra
      low-dose mifepristone for six months is associated with modest reduction in
      uterine size, appreciable improvements in symptoms and quality of life and no
      evidence of endometrial hyperplasia.

PMID- 19586709
TI  - Indications and results of labour induction in nulliparous women: an interview
      among obstetricians, residents and clinical midwives.
AB  - OBJECTIVE: To investigate which clinical factors are important in management
      decisions that clinicians make in the process of labour induction, and which
      clinical factors they estimate as predictive of labour outcome after induction.
      STUDY DESIGN: A written interview was conducted among obstetricians, residents
      and clinical midwives in five teaching hospitals in the south of the Netherlands.
      Sixteen fictive vignettes were constructed of pregnant nulliparous women who were
      candidates for induction of labour. The vignettes differed on eight clinical
      variables: maternal age, BMI, gestational age, indication for induction (maternal
      request vs mild pre-eclampsia), dilation, position, consistency and effacement of
      the cervix. For each case presentation, the inclination to induce labour was
      calculated for the three groups, and their estimates of the probability of a
      spontaneous vaginal delivery or a caesarean delivery were analyzed. RESULTS: Of
      the 80 questionnaires sent, 60 (75%) were completed. Mild pre-eclampsia and post
      term pregnancy were the most important clinical factors for the decision to
      induce or not in all three groups. Gestational age, effacement and dilation of
      the cervix were considered as the most important predictors of labour outcome
      after induction. CONCLUSIONS: In this interview, obstetricians, residents and
      clinical midwives based their decision-making whether or not to induce labour
      predominantly on medical indications. Outcome of labour after induction was
      estimated to depend on gestational age and cervical status at the start of
      induction.

PMID- 19586710
TI  - Water-quality effects of a mechanized subsurface-banding technique for applying
      poultry litter to perennial grassland.
AB  - Poultry litter is known to be an excellent organic fertilizer, but the common
      practice of spreading litter on the surface of pastures has raised serious water
      quality concerns and may limit potential benefits of litter applications. Because
      surface-applied litter is completely exposed to the atmosphere, runoff can
      transport nutrients into nearby streams and lakes, and much of the ammonium
      nitrogen volatilizes before it can enter the soil. Our previous research showed
      that a manual knifing technique to apply dry litter under a perennial pasture
      surface effectively prevented about 90% of nutrient loss with runoff from surface
      applied litter, and tended to increase forage yield. However, this technique
      (known as subsurface banding) cannot become a practical management option for
      producers until it is mechanized. To begin that process, we tested an
      experimental single-shank, tractor-drawn implement designed to apply poultry
      litter in subsurface bands. Our objective was to compare this mechanized
      subsurface-banding method against conventional surface application to determine
      effects on nutrient loss with runoff from a perennial grassland treated with dry
      poultry litter. Early in the growing season, broiler litter was applied (6.7 dry
      weight Mgha(-1)) to each plot (except three control plots) using one of two
      application methods: surface broadcast manually or subsurface banded using the
      tractor-drawn implement. Simulated rainfall (5cmh(-1)) generated 20min of runoff
      from each plot for volume and analytical measurements. Results showed that
      subsurface-banded litter increased forage yield while decreasing nutrient (e.g. N
      and P) loss in runoff by at least 90% compared to surface-broadcast litter.

PMID- 19586711
TI  - Re: Hendrik Isbarn, Jehonathan H. Pinthus, Leonard S. Marks, et al. Testosterone
      and prostate cancer: revisiting old paradigms. Eur Urol 2009;56:48-56.

PMID- 19586712
TI  - Tetrandrine induces apoptosis and growth suppression of colon cancer cells in
      mice.
AB  - Tetrandrine, a bisbenzylisoquinoline alkaloid, exerts antitumor effects against
      some cancers. We explored tetrandrine's effects on colon cancer with cultured
      mouse CT-26 cells and with subcutaneous tumors. Tetrandrine induced apoptosis in
      concentration- and time-dependent manner. Tetrandrine increased expression of ERK
      1/2 and p38 MAPK; inhibition of p38 MAPK reduced tetrandrine-induced apoptosis;
      inhibition of ERK1/2 did not. Tetrandrine had significant effects on tumors
      including slower growth and longer animal survival time and higher survival rate.
      Higher dose and earlier treatment were more effective than lower dose and delayed
      treatment. TUNEL staining showed prominent tetrandrine-induced apoptosis of
      tumors. These data suggest that tetrandrine induced significant apoptosis of
      cultured and subcutaneous CT-26 cells. Tetrandrine-induced apoptosis might be at
      least partially related to activation of the p38 MAPK signaling pathway.

PMID- 19586713
TI  - Ras activation contributes to the maintenance and expansion of Sca-1pos cells in
      a mouse model of breast cancer.
AB  - The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer
      and cause cancer metastasis and recurrence. In this study, we examined whether
      Ras signaling is associated with stemness of the CSCs population characterized by
      the stem cell antigen (Sca-1) phenotype in a 4T1 syngeneic mouse model of breast
      cancer. The Sca-1(pos) putative CSCs had high levels of activated Ras and
      phosphorylated MEK (p-MEK), compared with counterparts. The Ras farnesylation
      inhibitor (FTI-277) suppressed the maintenance and expansion of CSCs. Therefore,
      selective inhibition of Ras activation may be useful for stem-specific cancer
      therapy.

PMID- 19586714
TI  - Adsorption of Hg2+ from aqueous solution onto polyacrylamide/attapulgite.
AB  - Polyacrylamide/attapulgite (PAM/ATP) was prepared by the solution polymerization
      of acrylamide (AM) onto gamma-methacryloxypropyl trimethoxy silane (KH-570)
      modified attapulgite (ATP). PAM/ATP was characterized using Fourier transform
      infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The effects of
      contact time, adsorbent dosage, and pH of the initial solution on the adsorption
      capacities for Hg(2+) were investigated. The adsorption process was rapid; 88% of
      adsorption occurred within 5 min and equilibrium was achieved at around 40 min.
      The equilibrium data fitted the Langmuir sorption isotherms well, and the maximum
      adsorption capacity of Hg(2+) onto PAM/ATP was found to be 192.5 mg g(-1). The
      adsorption kinetics of PAM/ATP fitted a pseudo-second-order kinetic model. Our
      results suggest that chemisorption processes could be the rate-limiting steps in
      the process of Hg(2+) adsorption. Hg(2+) adsorbed onto PAM/ATP could be
      effectively desorbed in hot acetic acid solution, and the adsorption capacity of
      the regenerated adsorbents could still be maintained at 95% by the sixth cycle.

PMID- 19586715
TI  - Treatment of tetrachloroethylene-contaminated groundwater by surfactant-enhanced
      persulfate/BOF slag oxidation--a laboratory feasibility study.
AB  - The main objective of this study was to evaluate the feasibility of remediating
      tetrachloroethylene (PCE)-contaminated groundwater (with initial PCE
      concentration of approximately 20 mg L(-1)) via persulfate oxidation activated by
      basic oxygen furnace slag (S(2)O(8)(2-)/BOF slag) with the addition of
      biodegradable surfactant (Tween 80). Results indicate that only 15% of PCE can be
      removed in experiment with the addition of S(2)O(8)(2-) only (S(2)O(8)(2
      )/PCE=30/1). PCE removal can be increased to 31% while both S(2)O(8)(2-) and BOF
      slag (10 g L(-1)) were added. This indicates that BOF slag was able to activate
      the persulfate oxidation mechanism, and cause the decrease in PCE concentration
      via oxidation process. Results also reveal that PCE degradation rates increased
      to 92% with the presence of Tween 80 (S(2)O(8)(2-)/Tween 80/PCE=30/2/1). In the
      presence of 10 g L(-1) BOF slag, the reaction rate constant (k(obs)) values were
      found to be 3.1 x 10(-3), 8.7 x 10(-3), 1.6 x 10(-2), and 5.8 x 10(-2)h(-1), as
      the S(2)O(8)(2-)/Tween 80/PCE molar ratios were 30/0/1, 30/0.5/1, 30/1/1, and
      30/2/1, respectively. The reaction rate constant increased as the Tween 80
      concentration increased. The significantly increased k(obs) could be caused by
      the enhanced solubilization of PCE by Tween 80. The increase in initial
      surfactant concentration would cause the increase in the solubilization of PCE,
      and thus, enhance the oxidation rate. This was confirmed by the total amount of
      chloride ions produced after the reaction. Results from this study indicate that
      BOF slag-activated persulfate oxidation enhanced by surfactant addition is a
      potential method to efficiently and effectively remediate chlorinated solvents
      contaminated groundwater.

PMID- 19586716
TI  - Biosorption of chromium, copper and zinc by wine-processing waste sludge: single
      and multi-component system study.
AB  - Wine-processing waste sludge (WPWS) has been shown to have powerful potential for
      sorption of some heavy metals (i.e., chromium, lead and nickel) in single
      component aqueous solutions. But although most industrial wastewater contains two
      or more toxic metals, there are few sorption studies on multicomponent metals by
      WPWS. This study has two goals: (i) conduct competitive adsorption using Cr, Cu
      and Zn as sorbates and examine their interaction in binary or ternary systems;
      and (ii) determine the effects of temperature on the kinetic sorption reaction.
      The sludge tested contained a high amount of organic matter (38%) and had a high
      cation exchange capacity (CEC, 255 cmol(c)kg(-1)). Infrared analysis reveals that
      carboxyl is the main functional group in this WPWS. The (13)C NMR determination
      indicates alkyl-C and carboxyl-C are major organic functional groups. At steady
      state, there are about 40.4% (Cr), 35.0% (Cu) and 21.9% (Zn) sorbed in the
      initial 6.12 mM of single-component solutions. Only pseudo-second-order sorption
      kinetic model successfully describes the kinetics of sorption for all
      experimental metals. The rate constants, k(2), of Cr, Cu and Zn in single
      component solutions are 0.016, 0.030 and 0.154 g mg(-1)min(-1), respectively. The
      sorption of metals by WPWS in this competitive system shows the trend: Cr>Cu>Zn.
      Ions of charge, hydrated radius and electronic configuration are main factors
      affecting sorption capacity. The least sorption for Zn in this competitive system
      can be attributed to its full orbital and largest hydrated radius. Though the
      effect of temperature on Zn sorption is insignificant, high temperature favors
      the other metallic sorptions, in particular for Cr. However, the Cr sorption is
      lower than Cu at 10 degrees C. The Cr sorption by WPWS can be higher than that of
      Cu at 30 degrees and 50 degrees C.

PMID- 19586717
TI  - Decolourization and detoxification of pulp and paper mill effluent by Emericella
      nidulans var. nidulans.
AB  - In this study geno-toxicity analysis along with effluent treatment was taken up
      to evaluate the efficiency of biological treatment process for safe disposal of
      treated effluent. Four fungi were isolated from sediments of pulp and paper mill
      in which PF4 reduced colour (30%) and lignin content (24%) of the effluent on 3rd
      day. The fungal strain was identified as Emericella nidulans var. nidulans
      (anamorph: Aspergillus nidulans) on the basis of rDNA ITS1 and rDNA ITS2 region
      sequences. The process of decolourization was optimized by Taguchi approach. The
      optimum conditions were temperature (30-35 degrees C), rpm (125), dextrose
      (0.25%), tryptone (0.1%), inoculum size (7.5%), pH (5) and duration (24h).
      Decolourization of effluent improved by 31% with reduction in colour (66.66%) and
      lignin (37%) after treatment by fungi in shake flask. Variation in pH from 6 to 5
      had most significant effect on decolourization (71%) while variation in
      temperature from 30 to 35 degrees C had no effect on the process. Treated
      effluent was further evaluated for geno-toxicity by alkaline single cell gel
      electrophoresis (SCGE) assay using Saccharomyces cerevisiae MTCC 36 as model
      organism, indicated 60% reduction.

PMID- 19586718
TI  - Bioleaching of heavy metals from sewage sludge by indigenous iron-oxidizing
      microorganisms using ammonium ferrous sulfate and ferrous sulfate as energy
      sources: a comparative study.
AB  - The potential of indigenous iron-oxidizing microorganisms enriched at initial
      neutral pH of the sewage sludge for bioleaching of heavy metals was investigated
      at initial neutral pH of the sludge using ammonium ferrous sulfate (FAS) and
      ferrous sulfate (FS) as an energy sources in two different sets of experiments.
      After 16 days of bioleaching, 56% Cu, 48% Ni, 68% Zn and 42% C were removed from
      the sludge using ammonium ferrous sulfate as an energy source. On the other hand,
      64% Cu, 58% Ni, 76% Zn and 52% Cr were removed using ferrous sulfate. Further,
      32% nitrogen and 24% phosphorus were leached from the sludge using ferrous
      sulfate, whereas only 22% nitrogen and 17% phosphorus were removed using ammonium
      ferrous sulfate. The BCR sequential extraction study on speciation of metals
      showed that using ammonium ferrous sulfate and ferrous sulfate, all the metals
      remained in bioleached sludge as stable form (F4 fraction). The results of the
      present study indicate that the bioleached sludge would be safer for land
      application. Also, the fertilizing property was largely conserved in the
      bioleached sludge using both the substrates.

PMID- 19586719
TI  - Bench-scale tests on ultrasound-assisted acid washing and thermal desorption of
      mercury from dredging sludge and other solid matrices.
AB  - A series of ultrasonic assisted acid washing and thermal desorption tests were
      performed on sludge and other solid matrices with the aim to assay these removal
      technologies and to determine if the application of low frequency ultrasound was
      effective to enhance mercury removal. Unpolluted dredging sludge, 820 K
      calcinated dredging sludge, silica and alumina were characterized, polluted with
      a known concentration of mercury and treated both by acid washing and thermal
      desorption with and without low frequency ultrasound application. The acid
      washing was carried out by a 4% HNO(3) acid solution and the thermal desorption
      was performed in a 370-620K range. X-ray semi-quantitative analysis of dredging
      sludge before and after acid washing and granulometric curves of the matrices
      after the ultrasonic treatment were considered in order to evidence chemical or
      physical changes during these treatments. Total residual mercury measurements
      were carried out before and after sonication. Results showed not measurable acid
      washing extraction from polluted dredging sludge, a little (3%) extraction from
      820K heat-treated sludge and a significant (10-20%) extraction from alumina and
      silica within 120 min of treatment. The ultrasound application gave generally
      poor improvement of the mercury removal. On the contrary thermal desorption of
      mercury was somewhat effective for alumina, silica and heat-treated dredging
      sludge samples in which mercury removal was 30-40% at 370 K and 90-99% at 570 K.
      Likewise ultrasound application did not improve desorption. Instead, the thermal
      treatment of dredging sludge had a negligible amount of mercury desorption at 370
      K but it reached 95% at 570 K. The application of ultrasound improved the thermal
      extraction of 25% in the 470-520 K range of temperature.

PMID- 19586720
TI  - Using shell-tunable mesoporous Fe3O4@HMS and magnetic separation to remove DDT
      from aqueous media.
AB  - 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) is of concern in water
      treatment because of its persistence and health effects. A new concept is
      proposed to synthesize hexagonal mesoporous silica (HMS) with magnetic
      functionalization for DDT removal from aqueous media. Fe(3)O(4) nanocrystals were
      synthesized by a low-temperature solvothermal process, and then encapsulated in
      mesoporous silica through a packing approach, forming core-shell structured
      Fe(3)O(4)@HMS microspheres. The synthesized materials were characterized by X-ray
      diffraction (XRD), transmission electron microscopy (TEM) and nitrogen adsorption
      desorption techniques. The results indicate that the silica shell conserves
      mesoporous structure after the removal of surfactant templates. Different from
      previous studies, the thickness, pore volume and surface area of silica shell can
      be controlled by adjusting the reaction condition. These Fe(3)O(4)@HMS materials
      show high adsorption capacity and fast adsorption rate for DDT. Because of the
      useful magnetic property and unique mesoporous structure, the synthesized
      materials provide a fast, convenient and highly efficient means to remove DDT
      from aqueous media.

PMID- 19586721
TI  - Geochemical factors controlling the occurrence of high fluoride groundwater in
      the Nagar Parkar area, Sindh, Pakistan.
AB  - Fluoride concentrations in groundwater near Nagar Parkar in the Thar Desert of
      southeastern Pakistan range from 1.13 to 7.85 mg/l, and roughly 78% of the
      samples contain fluoride in concentrations that exceed the drinking water
      standard of 1.5mg/l set by WHO. The groundwater is alkaline (pH 7.1-8.4),
      brackish (TDS 449-15,933 mg/l), and classified as Na-Cl type water. This
      prevailing chemical character reflects the influence of saltwater intrusion, high
      evaporation rates, and ion exchange. Groundwater is also supersaturated with
      respect to calcite, which promotes the removal of Ca(2+) and HCO(3)(-) from
      solution. As a result, groundwater is generally undersaturated with respect to
      fluorite, the mineral that typically controls the upper limit of fluoride
      concentrations. This study examines a number of geochemical parameters in an
      effort to discover the controls on fluoride concentrations in groundwater. High
      fluoride concentrations are associated with high TDS, high pH, high Na
      concentrations, and high sodium absorption ratios (SAR). This suggests that
      elevated fluoride levels are the result of enhanced fluorite solubility due to Ca
      depletion and high ionic strength and the release of fluoride from colloid
      surfaces under high pH conditions. Contrary to what has been found in other
      studies, sample depth and water temperature do not appear to have a significant
      role in the distribution of fluoride within the groundwater.

PMID- 19586722
TI  - Pain language and gender differences when describing a past pain event.
AB  - Pain is a largely subjective experience, and one which is difficult to convey to
      others, and relies significantly on language to be communicated. The language
      used to describe pain is therefore an important aspect of understanding and
      assessing another's pain. A growing body of research has reported differences in
      the pain experienced by men and women. However, few studies have examined gender
      differences, where gender is understood in both the biological and the social
      sense, in the language used when reporting pain. The purpose of this descriptive
      and analytical study was to explore gender differences in the language used by
      articulate men and women when describing a recollected painful event. Two-hundred
      and one students from an Australian university (35.32% males and 64.68% females)
      provided written descriptions of a past pain event. These descriptions were
      analysed using content analysis. Gender differences were identified in the words
      and patterns of language used, the focus of pain descriptions, and the reported
      emotional response to pain. Women were found to use more words (t=4.87, p<0.001),
      more McGill Pain Questionnaire descriptors (chi(2)=3.07, p<0.05), more graphic
      language than men, and typically focused on the sensory aspects of their pain
      event. Men used fewer words, less descriptive language, and focused on events and
      emotions. Common themes were the functional limitations caused by pain,
      difficulty in describing pain, and the dual nature of pain. Clinical implications
      include the value of gathering free pain descriptions as part of assessment, and
      the use of written pain descriptions.

PMID- 19586723
TI  - How would you like your tea, vicar?
AB  - INTRODUCTION: Scald injuries are the commonest cause of paediatric burns leading
      to hospital admission both in the United Kingdom (National Burn Care Review
      Committee Report; 2001) and around the world. The cost and significant morbidity
      resulting from scald injuries reiterates the need for effective prevention
      campaigns for primary caregivers. The majority of scalds in children occur in the
      kitchen (49%) at home. Three children a day under the age of 5 (1100/year) are
      involved in scalds resulting from pulling on a cup of beverage onto themselves.
      We therefore aim to study the temperature of common beverages made at home and
      their potential to cause significant thermal injury. MATERIALS AND METHODS:
      Common household beverages were formulated to assess the thermal characteristics.
      Each beverage was made in a standardized environment with constant ambient
      temperature of 22 degrees C. Beverages were made in 230 ml ceramic mugs, using
      boiled water from an electric kettle, instant coffee granules and teabags. Hot
      milk and hot water were prepared for comparison. Temperature readings were taken
      from 0 to 10 min. Cooling curves were then plotted. RESULTS: Milky beverages had
      the lowest starting temperatures (75-77 degrees C). Black tea and black coffee
      remained at temperatures greater than 65 degrees C despite cooling for 10 min.
      The addition of sugar did not alter the cooling rate. Similarly there was very
      little difference in cooling rates for skimmed and full fat milk. Addition of 10
      ml rather than 5 ml of milk lowered the starting temperature and increased the
      cooling rates. DISCUSSION/CONCLUSION: Hot beverages can cause significant scald
      injuries especially in the paediatric population. We demonstrated the potential
      for a full thickness burn despite cooling for 10 min or the addition of cold
      milk. Thus the complacent attitude surrounding beverages under such conditions
      should be abolished. Our work also reiterates the need for education amongst
      caregivers regarding the handling of hot beverages in order to reduce the number
      of household injuries.

PMID- 19586724
TI  - WITHDRAWN: Aids denialism at the ministry of health.
AB  - This Article-in-Press has been permanently withdrawn. The editorial policy of
      Medical Hypotheses makes it clear that the journal considers "radical,
      speculative, and non-mainstream scientific ideas", and articles will only be
      acceptable if they are "coherent and clearly expressed." However, we received
      serious expressions of concern about the quality of this article. Given these
      important signals of concern, we commissioned an external expert panel to
      investigate the circumstances in which this article came to be published online.
      The panel recommended that the article should be externally peer-reviewed.
      Following a peer-review process managed by The Lancet editorial team, all five
      external reviewers recommended rejection, as a result of which the expert panel
      recommended permanent withdrawal. The Publisher apologizes for any inconvenience
      this may cause. The full Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 19586725
TI  - Light Hygiene: Time to make preventive use of insights--old and new--into the
      nexus of the drug light, melatonin, clocks, chronodisruption and public health.
AB  - Light is, clearly, a key to life on Earth and light, equally clearly, determines
      biological rhythmicity in organisms. Light does the latter by setting internal or
      endogenous clocks which allow a multitude of species, including man, to adjust
      their lives to changing external or environmental conditions. Critical changes
      over time occur from day to night and throughout the year. In this paper, we sum
      up how visible light provides electromagnetic information about environmental
      "time" via the ocular interface of newly discovered photoreceptive cells to a
      master clock in our brain, viz the suprachiasmatic nuclei [SCN], and how the SCN
      translate this input, with melatonin as a key biologic intermediary, into
      endogenous or biological time. We summarize experimental and epidemiological
      evidence suggesting how chronodisruption, a relevant disturbance of the temporal
      organization or order of physiology, endocrinology, metabolism and behaviour, is
      probably detrimental for human beings. On the basis of our synthesis, and in line
      with suggestions by other researchers voiced decades ago, light must,
      functionally, be considered as a drug equivalent. In this vein, the very timing,
      quality (wavelength), quantity (dose) and side effects, including
      chronodisruption, of light exposures can be critically important for health and
      disease in man. As a promising means to foster public health, we advocate an
      appropriate balance of exposures to the key Zeitgeber light in terms of "light
      hygiene", implying strong and appropriate rather than weak and confusing temporal
      information. This focus on "light hygiene", and thus on the key Zeitgeber light,
      does not mean to ignore that there are multiple entrainment pathways for our
      circadian clocks. Indeed, when dealing with light, chronodisruption and a
      multitude of adverse health effects, we ultimately need to consider Zeitgeber
      cues, and their possible interplay, beyond light alone. Confusions of the
      temporal programmes in humans can also stem from physical and social activities,
      stress and facets of food intake. And yet, since light possesses a rather unique
      and exclusive Zeitgeber role and in view of its ubiquitous nature, a specific,
      preventative focus on "light hygiene", as a contribution to a general "Zeitgeber
      hygiene", is warranted.

PMID- 19586726
TI  - Women and smoking: an interdisciplinary examination of socioeconomic influences.

PMID- 19586727
TI  - Income does not affect response to contingency management treatments among
      community substance abuse treatment-seekers.
AB  - The present study examined a commonly held belief that contingency management
      (CM) may be less effective for substance abusers with relatively more economic
      resources compared to those with relatively few resources. Using a combined
      sample of 393 treatment-seeking cocaine abusers from three clinical trials
      involving randomization to standard care or standard care plus CM conditions, we
      assessed the impact of past year income, alone and in combination with treatment
      condition, as well as income type (i.e., earned, illegal, unstable) on the
      longest duration of continuous verified abstinence (LDA) achieved during
      treatment. Results suggested that income had no effect on LDA in either
      condition, and that CM's effectiveness did not deteriorate among those with
      better economic resources in the present sample. This finding may be of value to
      clinicians and administrators who are considering the addition of CM to standard
      care treatments in community outpatient substance abuse clinics and have concerns
      about the generalizability of CM across clients with various economic resources.

PMID- 19586728
TI  - The cryoprotective effect of low-density lipoproteins in extenders on bull
      spermatozoa following freezing-thawing.
AB  - Egg low-density lipoprotein (LDL) was added at concentrations of 7-10% to the
      extenders used to freeze bull semen and its effects on the motility, mitochondria
      activity, acrosome integrity, membrane integrity and DNA integrity of frozen
      thawed sperm were assessed. Analysis of data showed that the motility and
      characteristics of spermatozoa movement were higher with LDL in the extender, as
      compared to the extender containing 20% egg yolk. The results indicated that 8%
      LDL supplementation provided the highest sperm motility (55.8%) and movement
      characteristics (VSL, straight linear velocity: 33.8 microm/s; VCL, curvilinear
      velocity: 50.2 microm/s; LIN, linearity index: 56.5%; STR, mean coefficient:
      76.7%; VAP, average path velocity: 35.9 microm/s; WOB, wobble coefficient:
      63.9%). A concentration of 10% LDL resulted in a significant decline in the VSL,
      LIN, VAP and WOB values (P<0.05). Supplementation of LDL at 8% LDL resulted in
      significantly higher spermatozoa mitochondrial activity, acrosome integrity,
      membrane integrity and DNA integrity (P<0.05). According to all measured
      parameters, the extender containing 8% LDL showed beneficial cryoprotective
      effects on frozen-thawed bull spermatozoa. In conclusion, our results indicated
      that the extender containing 8% LDL extracted from egg yolk could be used
      successfully in the cryopreservation of bull semen with an efficacy that would be
      greater than present extenders containing 20% egg yolk.

PMID- 19586729
TI  - Cryopreservation of Iberian pig spermatozoa. Comparison of different freezing
      extenders based on post-thaw sperm quality.
AB  - The aim of this study was to evaluate the cryoprotective effect of different
      freezing extenders against cryopreservation injuries on Iberian boar sperm. The
      sperm-rich fraction was collected and pooled from six sexually mature Iberian
      boars, and was frozen in different extenders containing glucose, lactose or
      fructose as sugar source and including Orvus ES Paste only in the freezing
      extender-2 (Glucose; Lactose and Fructose) or in both freezing extenders
      (Glucose2; Lactose2 and Fructose2). During the cryopreservation process, the
      supernatant was removed after the centrifugation step, then was extended with
      freezing extender-1 for the equilibration period and with freezing extender-2
      immediately before freezing. Post-thaw sperm characteristics, such as plasma
      membrane integrity (SYBR-14/PI), mitochondrial function (Rhodamine 123) and
      acrosome integrity (NAR), were monitored. Overall sperm motility and the
      individual kinematic parameters of motile spermatozoa (assessed by the computer
      aided sperm analysis system Sperm Class Analyzer [SCA]) were recorded in the
      different experimental treatments. Measurements were taken at 30 and 150 min post
      thaw. The state of the acrosome after thawing did not show significant
      differences between the freezing extenders studied. Freezing-thawing caused a
      significant decrease (P<0.001) in plasma membrane integrity and in mitochondrial
      activity in the spermatozoa frozen with Orvus ES Paste in both freezing
      extenders. Furthermore, spermatozoa frozen with Orvus ES Paste in both freezing
      extenders exhibited lower (P<0.05) motility and kinematic parameters than those
      frozen in the absence of Orvus ES Paste in the first freezing extender. The
      spermatozoa frozen with the Lactose extender and with Orvus ES Paste only in the
      second freezing extender showed a better evolution of the motility and kinematic
      characteristics (P<0.05) over time. The deterioration in post-thaw sperm motility
      and kinematic parameters were concurrent with reduced sperm characteristics. It
      can be suggested that in the Iberian pig, the beneficial effects of Orvus ES
      Paste during the freezing process of spermatozoa is time dependent. The analysis
      of different sperm characteristics such as motility, plasma membrane integrity
      and mitochondrial function, determined that the extenders studied in the present
      experiment affected the quality of frozen-thawed semen in Iberian boar.

PMID- 19586731
TI  - Suspected black cohosh hepatotoxicity--challenges and pitfalls of causality
      assessment.
AB  - OBJECTIVES: Black cohosh (BC) is a herbal drug or herbal dietary supplement used
      for treatment of menopausal symptoms. Recently, however, reports have appeared
      about the occurrence of rare toxic liver disease in an assumed relationship with
      the use of BC. METHODS: We have analyzed and reviewed the data of all 69 reported
      cases with suspected BC hepatotoxicity. Causality for BC was assessed utilizing
      the scale of the original structured quantitative Council for International
      Organizations of Medical Sciences (CIOMS), or the main-test as its updated form.
      RESULTS: With the hepatotoxicity specific causality assessment methods, there was
      an excluded, unlikely, unrelated or unassessable causality for BC in 68 of 69
      cases with liver disease. One patient had a possible causality for BC and a
      symptomatic cholelithiasis with confounding variables of fatty liver of unknown
      etiology; unknown BC brand including possible herbal mixture; unknown daily BC
      dosage; and an unassessable duration of BC usage. In general, the cases of the 69
      patients were poorly documented. Confounding variables were: failure to identify
      the BC product; use of herbal mixtures with multiple ingredients in addition to
      BC; co-medication with synthetic drugs and dietary supplements including herbal
      ones; missing temporal association between BC use and development of liver
      disease; not specified modalities of BC treatment; failure of dechallenge after
      BC discontinuation; pre-existing liver diseases; insufficiently excluded other
      liver diseases; presence of alternative liver diseases. CONCLUSIONS: The analysis
      of 69 cases shows little, if any, supportive evidence for a significant
      hepatotoxic risk of BC.

PMID- 19586730
TI  - Lambing rates and litter size following carazolol administration prior to
      insemination in Kivircik ewes.
AB  - The effect of carazolol on the ease of penetrating the cervix during artificial
      insemination, lambing rate and litter size was studied using 1.5-4.0-year old
      Kivircik ewes in an incomplete 3 x 2 x 2 experimental design. All of the ewes in
      this study were synchronized for oestrus by insertion of a progesterone
      impregnated vaginal sponge for 12 days and administration of 400 IU PMSG at
      sponge withdrawal. Three methods of service were compared: natural service,
      artificial insemination (AI) with fresh semen, or AI with frozen semen. Two times
      of insemination (fixed time AI versus AI at observed oestrus) were compared on
      the fresh and frozen AI treatments. The absence (control) or use of carazolol
      (carazolol; 0.5mg/ewe i.m. 30 min before mating) was the third factor in the
      design and penetration of the cervix by the insemination pipette was assessed as
      shallow (<10mm), middle (10-20mm) or deep (>20mm). Natural service ewes were only
      mated at observed oestrus. Consequently, the factorial design was incomplete and
      there were a total of 10 treatments each represented by 30 ewes. Natural service
      resulted in a significantly (P<0.05) higher lambing rate and litter size (86%;
      2.0+/-0.05 lambs/ewe) than AI using fresh (65%; 1.6+/-0.1 lambs/ewe) or frozen
      (40%; 1.4+/-0.14 lambs/ewe) semen. For AI animals the lambing rate and litter
      size were not significantly different when service was at a fixed time (50%;
      1.5+/-0.12 lambs/ewe) or at observed oestrus (56%; 1.5+/-0.12 lambs/ewe).
      Carazolol did not permit complete cervical penetration in any ewe. Deep
      penetration of the cervix at AI was achieved in 33% of untreated (control) and
      48% of carazolol treated ewes (P<0.05). However, the proportion of ewes in which
      penetration of the cervix and semen deposition was greater than shallow was
      similar for control (82%) and carazolol (85%), and lambing rate and litter size
      were similar for both treatments. Over the three service methods, the lambing
      rate was 56% for control and 63% for carazolol (NS) and litter size was similar
      for both treatments. It was concluded that the carazolol treatment used prior to
      natural mating or AI in this experiment did not improve lambing rate or litter
      size in Kivircik ewes.

PMID- 19586732
TI  - [Bordetella holmesii bacteremia in a 26-year-old patient with sickle cell
      disease].
AB  - Bordetella holmesii is a rare cause of bacteremia. It occurs mainly in
      hyposplenic patients, such as those affected by sickle cell anemia. The most
      frequent clinical signs are not very specific: fever, cephalalgia, cough,
      dyspnea, vomiting, etc. B. holmesii is frequently isolated from blood cultures.
      We describe the case of a 26-year-old sickle cell patient, presenting with dry
      cough and fever caused by a B. holmesii blood stream infection, identified by 16S
      rRNA gene sequencing. The outcome was favorable with amoxicillin. It is useful to
      know about B. holmesii, especially for physicians managing sickle cell or
      hyposplenic patients, because of its variable susceptibility to beta-lactams.

PMID- 19586733
TI  - Intraductal papillary mucinous neoplasms of the pancreas: correlation of helical
      CT features with pathologic findings.
AB  - OBJECTIVE: To evaluate the CT features of intraductal papillary mucinous
      neoplasms of the pancreas (IPMNs), and to compare with pathological findings in
      order to identify CT features that can be helpful in differentiating benign IPMNs
      from malignant IPMNs. MATERIALS AND METHODS: The CT findings in 25 patients were
      reviewed for tumor location, tumor type, dilatation of the main pancreatic duct
      (MPD), MPD involvement, mural node or solid attenuating component, tumor size in
      branch duct or mixed duct type, dilatation of common bile duct (CBD) and invasion
      of surrounding structures. The data was subjected to Chi-Square Tests or Fisher's
      Exact Test using SPSS13.0 software with p value<0.05 indicating significant
      statistical difference. RESULTS: Presence of mural node or solid enhancing
      component, size of mural node or solid enhancing component >=7mm, dilatation of
      CBD was more common in malignant IPMNs (p<0.05). None of tumor location, tumor
      type, dilatation of MPD, MPD involvement, tumor size, and invasion of surrounding
      structures was statistically significant in differentiating benign from malignant
      IPMNs. CONCLUSIONS: CT features suggestive of malignant or invasive IPMNs include
      presence of mural node or solid enhancing component, size of mural node or solid
      enhancing component >=7mm, and dilatation of CBD.

PMID- 19586734
TI  - Percutaneous treatment of bone tumors by radiofrequency thermal ablation.
AB  - We present our experience of the treatment of bone tumors with radiofrequency
      thermal ablation (RFTA). Over the past 4 years, we have treated 26 cases (22
      benign and 4 malignant) using CT-guided RFTA. RFTA was the sole treatment in 19
      cases and was combined with percutaneous cementation during the same session in
      the remaining seven cases. Our approach to the tumors was simplified, using a
      single point of entrance for both RFTA and percutaneous osteoplasty. In the
      benign cases, clinical success was defined as resolution of pain within 1 month
      of the procedure and no recurrence during the follow-up period. It was achieved
      in 19 out of the 21 patients in which curative treatment was attempted. The two
      non-resolved cases were a patient with osteoid osteoma who developed a
      symptomatic bone infarct after a symptom-free period of 2 months and another with
      femoral diaphysis osteoblastoma who suffered a pathological fracture after 8
      months without symptoms. The procedure was considered clinically successful in
      the five cases (4 malign and 1 benign) in which palliative treatment was
      attempted, because there was a mean (+/-SD) reduction in visual analogue scale
      (VAS) pain score from 9.0+/-0.4 before the procedure to <4 during the follow-up
      period.

PMID- 19586735
TI  - Characterization of aspartame-cyclodextrin complexation.
AB  - The inclusion complex formation of aspartame (guest) and various cyclodextrins
      (host) were examined using 1H NMR titration and capillary electrophoresis.
      Initially the protonation constants of aspartame were determined by NMR-pH
      titration with in situ pH measurement to yield log K1=7.83 and log K2=2.96. Based
      on these values the stability of the complexes formed by aspartame and 21
      different cyclodextrins (CDs) were studied at pH 2.5, pH 5.2 and pH 9.0 values
      where aspartame exists predominantly in monocationic, zwitterionic and
      monoanionic form, respectively. The host cyclodextrin derivatives differed in
      various sidechains, degree of substitution, charge and purity so that the effect
      of these properties could be examined systematically. Concerning size, the seven
      membered beta-cyclodextrin and its derivatives have been found to be the most
      suitable host molecules for complexation. Highest stability was observed for the
      acetylated derivative with a degree of substitution of 7. The purity of the CD
      enhanced the complexation while the degree of substitution did not provide
      obvious consequences. Finally, geometric aspects of the inclusion complex were
      assessed by 2D ROESY NMR and molecular modelling which proved that the guest's
      aromatic ring enters the wider end of the host cavity.

PMID- 19586736
TI  - Development of HPLC fingerprints for Mallotus species extracts and evaluation of
      the peaks responsible for their antioxidant activity.
AB  - Some Mallotus species are used in traditional medicine in Vietnam. To use certain
      species in Western medicines or as food supplements, they should be identified
      and quality control should be more strict, for instance, to avoid the erroneous
      switching of species. In species with interesting activities, the compounds
      responsible for them should be identified. For these identifications, HPLC
      fingerprint methodology can be used. In this paper, HPLC fingerprints of
      different lengths were developed for a number of Mallotus species. Secondly, a
      multivariate regression model was constructed to model the antioxidant activity
      of the Mallotus samples from the HPLC fingerprints with the aim to indicate peaks
      possibly responsible for this activity. For this purpose, after data
      pretreatment, the calibration technique partial least squares (PLS) was applied.

PMID- 19586737
TI  - [Expert's formalized recommendations. Glycemic control in ICU and during
      anaesthesia: useful recommendations].

PMID- 19586739
TI  - [Peroperative myocardial infarction, which treatment at the acute period?].
AB  - We report the case of a patient who presented, during a hip replacement, a
      cardiogenic shock following a myocardial infarction. After a successful
      resuscitation of three cardiac arrests, an intra-aortic balloon pump was
      inserted, then the patient could have been transferred to the nearest cardiac
      catheterization laboratory for a percutaneous dilatation of the right coronary
      artery, allowing the patient to have favourable outcome. Treatment of
      perioperative myocardial infarction is not really standardized. This case report
      depicts that in such critical condition, insertion of an intra-aortic balloon
      pump with early percutaneous angioplasty for acute peroperative myocardial
      infarction is a valuable option.

PMID- 19586738
TI  - [Single lung ventilation techniques in children].

PMID- 19586740
TI  - [Severe head trauma: good practices in 2009, before and during surgery].

PMID- 19586741
TI  - [Late refractory intracranial hypertension treated by decompressive craniectomy
      in severe herpetic encephalitis].

PMID- 19586742
TI  - [Blood salvage in paediatric surgery: situations at risk of haemorrhage, salvage
      strategies and their limits].

PMID- 19586743
TI  - Mechanical ventilation in paediatric intensive care.

PMID- 19586744
TI  - [Risks in paediatric anaesthesia].

PMID- 19586745
TI  - [Severe differed respiratory depression after intrathecal administration of
      morphine and clonidine on a 70-year-old patient].
AB  - We report a case of severe and differed respiratory depression to a 70-year-old
      patient after spinal anaesthesia for prostatic adenomectomy. Ten milligram of
      bupivacaine, 30 microg of clonidine and 100 microg of morphine has been
      administrated intrathecally. The anaesthesia has lasted 4h and, 16h after the
      induction, the patient had a respiratory depression with bradypnea (5c/min),
      hypoxia (SpO(2) 80%) and sedation (scale 3 of Wilson). The evolution was
      favourable after intravenous injection of naloxone and oxygenotherapy. The use of
      low dose intrathecal morphine can involve a respiratory depression. Intrathecal
      association of morphine and clonidine must be careful used among old patients and
      require a monitoring during the first 24h.

PMID- 19586746
TI  - [Morbidity and mortality linked to paediatric anaesthesia in the Maghreb].

PMID- 19586747
TI  - [Pain management after thoracotomy in children].

PMID- 19586748
TI  - [Acute renal dysfunction: it's time to speak appropriately!].

PMID- 19586749
TI  - [Hydroxyethylstarches: discussion, clarity and traceability].

PMID- 19586750
TI  - [Daily life, pregnancy, and quality of life after liver transplantation].
AB  - It is now accepted that patients with a liver transplantation regain the ability
      to lead a normal life within months of surgery, but at the price of lifetime
      immunosuppressive treatment and specific regular surveillance. A balanced and
      diversified diet, together with regular physical activity is necessary to
      prevent, limit, or delay the development of the cardiovascular complications that
      determine the prognosis for long-term survival. Attenuated live vaccines are
      contraindicated in patients treated with immunosuppressants to avoid the risk of
      reversion of the attenuation of the virus or bacteria. Travel abroad is possible
      to places with good sanitary conditions, if the patient increases his or her
      vigilance for any contagious infection. The global incidence of cancer is higher
      than in the general population, justifying specific and regular testing and
      clinical monitoring. A planned pregnancy is possible in patients stabilized after
      liver transplantation, and prognosis is most often good for mother and child.
      Early multidisciplinary management is essential because of the elevated risks of
      fetal growth restriction and preterm delivery. The global perception of quality
      of life increases after liver transplantation, but remains lower than in healthy
      subjects.

PMID- 19586751
TI  - Clinical effectiveness of a cognitive behavioral group treatment program for
      anxiety disorders: a benchmarking study.
AB  - Previous research has established efficacy of cognitive behavioral therapy (CBT)
      for anxiety disorders, yet it has not been widely assessed in routine community
      clinic practices. Efficacy research sacrifices external validity to achieve
      maximum internal validity. Recently, effectiveness research has been advocated as
      more ecologically valid for assessing routine clinical work in community clinics.
      Furthermore, there is a lack of effectiveness research in group CBT. This study
      aims to extend existing research on the effectiveness of CBT from individual
      therapy into group therapy delivery. It aimed also to examine outcome using not
      only symptom measures, but also measures of related symptoms, cognitions, and
      life quality and satisfaction. Results from a cohort of patients with various
      anxiety disorders demonstrated that treatment was effective in reducing anxiety
      symptoms to an extent comparable with other effectiveness studies. Despite this,
      only 43% of individuals showed reliable change, and 17% were 'recovered' from
      their anxiety symptoms, and the post-treatment measures were still significantly
      different from the level of anxiety symptoms observed in the general population.

PMID- 19586752
TI  - Construct validity and vulnerability to anxiety: a cognitive interviewing study
      of the revised Anxiety Sensitivity Index.
AB  - The Anxiety Sensitivity Index (ASI; Reiss, S., Peterson, R. A., Gursky, D. M., &
      McNally, R. J. (1986). Anxiety sensitivity, anxiety frequency and the prediction
      of fearfulness. Behaviour Research and Therapy, 24, 1-8) is probably the most
      widely used measure of cognitive vulnerability to anxiety. However, there have
      been periodic doubts expressed about whether it measures beliefs about the
      negative consequences of anxiety symptoms, as it purports to, or actual anxiety
      experiences. The present study investigated the construct validity of the revised
      ASI using a cognitive interviewing approach. Sixteen outpatients with anxiety
      problems responded to ASI-R items and items from another measure of vulnerability
      to anxiety, the Anxiety Attitude and Belief Scale, while thinking aloud. The
      resulting verbal protocols were coded according to the apparent cognitive
      processes respondents engaged in when answering the items. Responses to the
      revised ASI-R more often entailed retrieval of past episodes of anxiety, and
      participants more frequently formulated their responses based on judgments of the
      occurrence or intensity of feelings rather than on the appraisal of anticipated
      consequences of what was described in the items. These findings potentially have
      significant implications for interpretation of results from the large body of
      literature using the different versions of the ASI.

PMID- 19586753
TI  - Auditory changes in patients undergoing orthognathic surgery.
AB  - During orthognathic surgery, especially on the maxilla, osteotomies and
      displacements cause paratubular muscle dysfunction due to edema and muscle
      traction. This can cause auditory dysfunction. The aim of this study was to
      determine the effects of orthognathic surgery on the auditory status of patients.
      54 consecutive patients who met the inclusion criteria underwent audiometric
      tests 24h preoperatively, and 48 h 6 weeks and 8 weeks postoperatively (2 weeks
      after maxillomandibular fixation removal). Surgery was on the maxilla, mandible
      or both. The types of movements were recorded. Audiometric examinations included
      pure tone audiometry, tympanometry and Eustachian tube function test. In the
      maxillary and bimaxillary procedures, there was some auditory system dysfunction
      (p<0.05). At the end of the study, a few patients had some mild dysfunction
      (p<0/05). In conclusion, orthognathic surgery (mainly maxillary and bimaxillary
      procedures) can cause some auditory system dysfunction, which is mild and
      transient in most cases and requires no intervention.

PMID- 19586754
TI  - Prevention of the ultraviolet effects on clinical and histopathological changes,
      as well as the heat shock protein-70 expression in mouse skin by topical
      application of algal UV-absorbing compounds.
AB  - BACKGROUND: Sunscreens have long been used to protect against the acute effects
      of UV radiation. They can also have protective effects on chronic UV-induced
      changes, such as photoaging and skin cancer. Recent studies have focused on
      marine organisms as a source of natural bioactive molecules and some UV-absorbing
      algal compounds are under investigation as candidates for new natural sunscreens.
      OBJECTIVE: The cutaneous photoprotective ability of the mycosporine-like
      aminoacids (MAAs) Porphyra-334 and shinorine (P-334+SH), high UV-absorbing
      compounds isolated from the red alga Porphyra rosengurttii, was evaluated by in
      vivo procedures in mouse skin. The expression of the heat shock protein HSP70 as
      a potential biomarker for acute UV damage was also investigated. METHODS: A
      galenic formulation containing the MAA combination of P-334+SH was applied
      topically to the dorsal skin of SkhR-1 H hairless mice, which were irradiated
      with a single UV radiation dose of 3.87Jcm(-2) and compared with a combination of
      UVB- and UVA-absorbing reference filters. Clinical signs of sunburn, such as
      erythema and edema, as well as other quantifiable histological and biochemical
      parameters, such as the expression of the heat shock protein 70 and antioxidant
      enzyme activities, were measured from skin biopsies at 6, 24, 48 and 72h post
      radiation. RESULTS: The formulation containing MAA prevented sunburn cell
      formation, as well as corneum stratum, malphigian, dermal and hypodermal
      thickening and other structural and morphological alterations observed in
      biopsies of non-photoprotected skin. A significant increase in Hsp70 was observed
      in the epidermis of non-photoprotected mouse skin, besides a de novo expression
      in deeper layers. P-334+SH protected against the significant decrease in
      superoxide dismutase and catalase activities observed in non-photoprotected mice.
      CONCLUSION: The topical application of P-334+SH protected against UV-induced skin
      damage in mice and contributed to maintaining the antioxidant defence system of
      the skin as well as Hsp70 expression.

PMID- 19586755
TI  - Effect of basic fibroblast growth factor (FGF2) gene polymorphisms on SSRIs
      treatment response and side effects.
AB  - Antidepressant response usually appears in 2 to 4 weeks and 30-40% of patients do
      not show a significant response although biochemical changes of monoaminergic
      system occur within hours after administration. Genetic factors could play a role
      in this process and genes involved in synaptic plasticity and neurogenesis are
      possible candidates. In fact, antidepressants and electroconvulsive therapy
      increase basic fibroblast growth factor (FGF2) and the rs1449683C/T polymorphism
      within this gene has been found to be a predictor for both an elevated mRNA and
      protein level of FGF2. Therefore we examined the possible association of
      rs1449683C/T and a panel of tagging SNPs in SSRI efficacy and side effects in 144
      Japanese major depressive subjects followed for 6 weeks. We observed a
      significant association of rs1449683T (p=0.010) and rs308393C (p=0.029) variant
      carriers toward a better response to SSRI and of rs1048201 with higher frequency
      of drop out due to side effects (p=0.010), independently from clinical variables.
      Furthermore the rs308447T-rs308393C-rs1449683T haplotype was associated with
      higher response rate (p=0.012) while the rs1048201T-rs3747676T haplotype was
      significantly associated with higher dropped out rate (p=0.015). In conclusion,
      this is the first study investigating the association of antidepressant response
      and intolerance with FGF2 variants. This finding adds an important piece of
      information for the pathway of detecting the genetics of antidepressant response.

PMID- 19586756
TI  - Controlled release of dual drugs from emulsion electrospun nanofibrous mats.
AB  - The purpose of this work is to develop a novel type of tissue engineering
      scaffold or drugs delivery carrier with the capability of encapsulation and
      controlled release drugs. In this study, Rhodamine B and Bovine Serum Albumin
      (BSA) were successfully incorporated into nanofibers by means of emulsion
      electrospinning. The morphology of composite nanofibers was studied by Scanning
      Electron Microscopy (SEM). The composite nanofibrous mats made from emulsion
      electrospinning were characterized by water contact angle measurement and X-ray
      diffraction. In vitro dual drugs release behaviors from composite nanofibrous
      mats were investigated. The results indicated that the incorporated drug and/or
      proteins in composite fibrous mats made from electrospinning could be control
      released by adjusting the processes of emulsions preparation.

PMID- 19586757
TI  - A double injection ADSA-CSD methodology for lung surfactant inhibition and
      reversal studies.
AB  - This paper presents a continuation of the development of a drop shape method for
      film studies, ADSA-CSD (Axisymmetric Drop Shape Analysis-Constrained Sessile
      Drop). ADSA-CSD has certain advantages over conventional methods. The development
      presented here allows complete exchange of the subphase of a spread or adsorbed
      film. This feature allows certain studies relevant to lung surfactant research
      that cannot be readily performed by other means. The key feature of the design is
      a second capillary into the bulk of the drop to facilitate addition or removal of
      a secondary liquid. The development will be illustrated through studies
      concerning lung surfactant inhibition. After forming a sessile drop of a basic
      lung surfactant preparation, the bulk phase can be removed and exchanged for one
      containing different inhibitors. Such studies mimic the leakage of plasma and
      blood proteins into the alveolar spaces altering the surface activity of lung
      surfactant in a phenomenon called surfactant inhibition. The resistance of the
      lung surfactant to specific inhibitors can be readily evaluated using the method.
      The new method is also useful for surfactant reversal studies, i.e. the ability
      to restore the normal surface activity of an inhibited lung surfactant film by
      using special additives. Results show a distinctive difference between the
      inhibition when an inhibitor is mixed with and when it is injected under a
      preformed surfactant film. None of the inhibitors studied (serum, albumin,
      fibrinogen, and cholesterol) were able to penetrate a preexisting film formed by
      the basic preparation (BLES and protasan), while all of them can alter the
      surface activity of such preparation when mixed with the preparation. Preliminary
      results show that reversal of serum inhibition can be easily achieved and
      evaluated using the modified methodology.

PMID- 19586758
TI  - [Pharmacotherapy of children with depressive disorders].
AB  - Many reviews exist about the use of psychotropic in children with depression
      (American academy of child and adolescent psychiatry en 2007 [Aacap] 2007, Food
      and drug administration [FDA] 2004, Afssaps 2008). Antidepressants are the most
      important long-term treatment: only fluoxetine has been effective and is
      authorised in France since August 2006. The risk of suicidality and sexual
      maturation alteration need to be control. Psychotherapy is needed to involve
      efficacy and tolerability treatment. Other IRS and IRSNA are used, but another
      study must be conducted in currently practice condition.

PMID- 19586759
TI  - [A lumbar cutaneous mass in a child].

PMID- 19586760
TI  - [High-dose intravenous immunoglobulin therapy and neonatal jaundice due to red
      blood cell alloimmunization].
AB  - Neonatal jaundice resulting from immunological hemolysis is not uncommon. While
      it is possible to prevent a large number of Rh-isoimmune hemolytic diseases by
      administration of specific anti-D immunoglobulins to the mother, the prevention
      of incompatibility in the ABO groups is not feasible. In spite of advances made
      in the use of phototherapy, and in order to avoid kernicterus, the treatment of
      these jaundices can require one or several exchange transfusions (ET), a therapy
      which is not devoid of risk. For some time now, the data concerning the
      efficiency of high-dose intravenous immunoglobulin therapy (HDIIT) in the
      treatment of these jaundices have been increasing. A review of the literature
      shows that, if used as soon as possible in newborn infants over 32 weeks of
      gestation age, afflicted with Rh or ABO hemolytic disease, the HDIIT brings
      about, with no undesirable side effects, a significant decrease in the ET number
      as well as a significant reduction in the length of phototherapy and
      hospitalization. The data suggesting that HDIIT could increase the risk of late
      transfusion is open to controversy.

PMID- 19586761
TI  - [Retro- and parapharyngeal infections: standardization of their management].
AB  - AIM: To analyze the changes in the management of retropharyngeal and
      parapharyngeal infections and propose a decisional algorithm for their diagnosis
      and treatment. PATIENTS AND METHODS: A retrospective survey was carried out in a
      tertiary care pediatric hospital between January 2001 and December 2005. All
      children aged less than 15 years and affected by a retro- or parapharyngeal
      infection were included. Clinical, biological, and radiological data, medical and
      surgical treatment, and complications were extracted from the review of medical
      charts. The results of the surgical findings were correlated with a cervical
      computed tomographic scan (CT scan). RESULTS: Thirty-one patients were included,
      64.5% during the last 2 years of the study period. All children presented fever
      and a stiff neck. The pharyngeal examination revealed a retropharyngeal bulge in
      a quarter of the population and an upper respiratory tract infection was
      concomitant in 68% of cases. A CT scan was carried out in 29 of 31 children
      (93.5%), with the radiological diagnosis of an abscess in 16 children (55.2%),
      presuppurative adenitis in 8 children (27.6%), and cellulitis in 5 children
      (17.2%). The CT scan was performed within 0.75 days of admission in 2001 and 2.3
      days in 2005. All children were treated with intravenous antibiotic therapy: an
      association of amoxicillin/clavulanic acid and an aminoglycoside in most cases.
      The mean duration of intravenous antibiotic therapy was 5.2 days. Seventeen
      patients (93.5%) underwent surgical drainage and purulent material was found in
      82.3% of cases. The accuracy of the CT scan, confirmed by surgical finding of a
      purulent material, was 71.4% in correctly identifying an abscess. The mean
      duration of surgical treatment after admission increased from 1.7 days in 2001 to
      3.3 days in 2005. The number of patients who underwent surgery was divided by a
      factor of 3 in the second period of the study. Two groups were compared: group A
      (n=12) treated with antibiotic therapy and group B (n=17) treated with
      antibiotics and surgical drainage. No significant difference was found between
      the two groups considering the duration of parenteral and oral antibiotic
      therapy, the standardization of cervical mobility, the mean time for apyrexia,
      and the length of hospitalization. There was one recurrence in group B 1 month
      later, and one case of sepsis in group A. None of the patients with
      retropharyngeal infection died. CONCLUSION: Without clinical evidence of severe
      sepsis, parenteral antibiotic therapy is recommended as the first-line treatment
      for children over 6 months of age presenting with retropharyngeal and
      parapharyngeal infections. If the clinical and/or biological conditions do not
      improve within 48-72h, a CT scan is indicated to assess the extent of infection
      and exclude complications. The decision to initiate surgical drainage depends on
      the patient's clinical status and the accessibility of the abscess.

PMID- 19586762
TI  - [Skin markers of communicating dermal sinus: report of two cases].
AB  - Skin abnormalities in the spinal lumbosacral region of infants are not
      infrequent. Physicians should look for underlying spinal malformations. We report
      2 cases of dermal sinus in infants revealed by severe, acute meningitis. The
      dermal sinus is an abnormal tract between the skin and underlying neural
      structures, most often located in the lumbosacral region. It may end blindly in
      the subcutaneous tissues, or it may extend into the medullary space. The
      diagnosis should be suspected in patients with other skin findings: localized
      hypertrichosis, subcutaneous lipomas, hyperpigmented lesions, etc. It must be
      distinguished from the very frequent coccygeal pits (4% of newborns), which
      require no treatment. Magnetic resonance imaging should be done every time the
      diagnosis is suspected. Recurrent bacterial meningitis or meningitis caused by
      unusual bacteria is frequently associated with dermal sinus. A variety of
      neurologic abnormalities have been described: sensory changes, motor weakness,
      reflex changes, abnormal bowel and bladder function, etc. Infants generally have
      few neurologic symptoms, such as delayed walking or sphincter control.
      Orthopaedic abnormalities are rare. The dermal sinus tract needs to be detected
      at an early stage in order to avoid these complications, which can be prevented
      by early surgery.

PMID- 19586763
TI  - [Congenital bronchobiliary fistula: a case report].
AB  - Congenital bronchobiliary fistulas (CBBF) are rare developmental anomalies. We
      report a case of a 6-day-old newborn who presented with respiratory distress and
      bilioptysis, originally involving a meconium aspiration syndrome. The diagnosis
      was confirmed by bronchoscopy. Surgery was performed at the age of 26 days and
      the newborn died the following day. Operative opacification showed communication
      between the carina and the biliary system. We review the clinical characteristics
      of CBBF and the value of early diagnosis and surgical treatment to prevent
      pulmonary complications due to bile salts.

PMID- 19586764
TI  - Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza
      virus and has a synergistic effect with oseltamivir.
AB  - Influenza epidemics cause numerous deaths and millions of hospitalizations each
      year. Because of the alarming emergence of resistance to anti-influenza drugs,
      there is a need to identify new naturally occurring antiviral molecules. We
      tested the hypothesis that pomegranate polyphenol extract (PPE) has anti
      influenza properties. Using real time PCR, plaque assay, and TCID 50%
      hemagglutination assay, we have shown that PPE suppresses replication of
      influenza A virus in MDCK cells. PPE inhibits agglutination of chicken red blood
      cells (cRBC) by influenza virus and is virucidal. The single-cycle growth
      conditions indicated that independent of the virucidal effect PPE also inhibits
      viral RNA replication. PPE did not alter virus ribonucleoprotein (RNP) entry into
      nucleus or translocation of virus RNP from nucleus to cytoplasm in MDCK cells. We
      evaluated four major Polyphenols in PPE (ellagic acid, caffeic acid, luteolin,
      and punicalagin) and demonstrated that punicalagin is the effective, anti
      influenza component of PPE. Punicalagin blocked replication of the virus RNA,
      inhibited agglutination of chicken RBC's by the virus and had virucidal effects.
      Furthermore, the combination of PPE and oseltamivir synergistically increased the
      anti-influenza effect of oseltamivir. In conclusion, PPE inhibited the
      replication of human influenza A/Hong Kong (H3N2) in vitro. Pomegranate extracts
      should be further studied for therapeutic and prophylactic potential especially
      for influenza epidemics and pandemics.

PMID- 19586765
TI  - Nitric oxide diffusing capacity versus spirometry in the early diagnosis of
      emphysema in smokers.
AB  - The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary
      capillary blood volume and equals the membrane diffusing capacity. Therefore the
      DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We
      measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA)
      and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly
      selected heavy smokers. Subjects with areas > or =1% of the total lung volume
      showing an attenuation <-950 Hounsfield Units were considered to have emphysema.
      In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94
      subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the
      ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the
      KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher
      sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive
      predictive value of KNO however was low (34.7%), while the negative predictive
      value of KNO was very high (98.2%), indicating an emphysema exclusion test. The
      DLNO/DLCO ratio is significantly higher in the study group compared to normal
      subjects.

PMID- 19586766
TI  - Homogeneous noncompetitive assay of protein via Forster-resonance-energy-transfer
      with tryptophan residue(s) as intrinsic donor(s) and fluorescent ligand as
      acceptor.
AB  - Homogeneous noncompetitive assay of a protein in biological samples based on
      Forster-resonance-energy-transfer (FRET) was proposed by using its tryptophan
      residues as intrinsic donors and its specific fluorescent ligand as the FRET
      acceptor that was defined as an analytical FRET probe. Conjugate of a suitable
      fluorophore, which should have an excitation peak around 340 nm but an excitation
      valley around 280 nm, with a moiety binding to a protein of interest gave an
      analytical FRET probe to the protein. To test this method, N-biotinyl-N'-(1
      naphthyl)-ethylenediamine (BNEDA) was used as an analytical FRET probe for
      homogeneous noncompetitive assay of streptavidin (SAV). The occurrence of FRET
      between the bound BNEDA and tryptophan residues was supported by the modeled
      geometry of the complex. By excitation at 280 nm, free BNEDA produced negligible
      fluorescence at 430 nm, but the bound BNEDA produced much higher stable
      fluorescence at 430 nm after 2 min of binding reaction. The competitive binding
      between BNEDA and biotin gave the dissociation constant of (16+/-3) fM for BNEDA
      (n=3). By excitation at 280 nm, fluorescence at 430 nm of reaction mixtures
      containing 32.0 nM BNEDA responded linearly to SAV subunit concentrations ranging
      from 0.40 to 30.0 nM with the desirable resistance to common interferences in
      biological samples. Therefore, by using tryptophan residue(s) in a protein of
      interest as intrinsic donor(s) and its fluorescent ligand as the corresponding
      FRET acceptor, this homogeneous noncompetitive assay of the protein in biological
      samples was effective and advantageous.

PMID- 19586767
TI  - Endocrine carcinoma of the major papilla: report of two cases and review of the
      literature.
AB  - To date, about 100 cases of ampullary NET are reported in International
      literature. These tumors can cause symptoms mainly secondary to their
      periampullary location. Up to 25% of patients have von Recklinghausen's disease.
      Carcinoid syndrome is uncommon, unless hepatic metastasis is present.
      Determination of histopathology is of utmost importance and involves specific
      immunohistochemical staining. The published data indicate that these tumors,
      metastasize in approximately half of cases irrespective of primary tumor size.
      Therefore, radical excision in the form of pancreaticoduodenectomy is recommended
      regardless of tumor size. Local excision should be confined to patients unable to
      tolerate more extensive surgery. We here report two case of ampullary
      neuroendocrine tumors presenting as melena and painless jaundice respectively in
      a 51-year old man and in a 54-year old man and review the relevant literature,
      giving special attention to the morphologic features, clinical characteristics,
      and treatment modalities associated with this disease process.

PMID- 19586768
TI  - Population dynamics at digester overload conditions.
AB  - Two different case studies concerning potential overload situations of anaerobic
      digesters were investigated and mathematically modelled by means of the Anaerobic
      Digestion Model No. 1 (ADM1). The first scenario included a digester failure at a
      municipal WWTP which occurred during revision works of the upstream digester
      within a two-step digestion system when the sludge was directly by-passed to the
      2nd-step reactor. Secondly, the non-occurrence of a highly expected upset
      situation in a lab-scale digester fed with cattle manure was investigated. ADM1
      was utilized to derive indicators which were used to investigate the relationship
      between digester stability and biomass population dynamics. Conventional design
      parameters such as the organic loading rate appeared unsuitable for process
      description under dynamic conditions. Indicators reflecting the biokinetic state
      (e.g. F(net)/M(net) or the VFA/alkalinity ratio) are more adequate for the
      assessment of the stability of reactors in transient situations.

PMID- 19586769
TI  - FXR agonist activity of conformationally constrained analogs of GW 4064.
AB  - Two series of conformationally constrained analogs of the FXR agonist GW 4064 1
      were prepared. Replacement of the metabolically labile stilbene with either
      benzothiophene or naphthalene rings led to the identification of potent full
      agonists 2a and 2g.

PMID- 19586770
TI  - Pure monoparesis of the leg due to cerebral infarctions: a diffusion-weighted
      imaging study.
AB  - Pure monoparesis of the leg due to cerebral infarction is rare compared to that
      of the hand. The anterior cerebral artery (ACA) territory is the most common
      lesion site in leg monoparesis, but diffusion-weighted (DW) MRI has not commonly
      been used for lesion detection. The purpose of this study was to use DW MRI to
      evaluate the radiological correlation with lesion location in patients presenting
      with pure leg monoparesis. We retrospectively studied six cerebral infarct
      patients with pure leg monoparesis who had undergone DW MRI. Patients were
      scanned within 3 days of symptom onset. DW MRI identified lesions in the
      posterior limb of the internal capsule (PLIC) in two patients, in the corona
      radiata (two patients), in the subcortical white matter of the posterior frontal
      lobe (one patient), and in the frontal and parietal cortex, including the
      paracentral lobule and precuneus (one patient). The two patients with PLIC
      infarctions had characteristic linear infarction abnormalities along the long
      axis of the internal capsule. Corona radiata infarction were located posteriorly,
      and the two subcortical and cortical infarction were thought to be in the
      territory of the ACA. We thus concluded that in leg monoparesis due to
      infarctions, lesions may be located in the PLIC, corona radiata, or in the ACA
      territory. Recently, magnetic resonance tractography has shown that foot fibres
      of the corticospinal tract in the PLIC somatotopically may be posteromedial to
      hand fibres along the short axis of the internal capsule, rather than
      posterolateral along the long axis as has been thought. Thus, damage along the
      long axis of the PLIC by linear infarctions can cause pure monoparesis of the
      leg.

PMID- 19586771
TI  - Giant intradiploic epidermoid cyst of the occipital bone.
AB  - Epidermoid cysts are uncommon, benign and slow-growing lesions. They often reach
      an enormous size without producing neurologic symptoms. We describe a 35-year-old
      female who had a giant intradiploic epidermoid cyst of the occipital bone. She
      underwent posterior cranial fossa tumor resection. Pathology confirmed epidermoid
      cyst. There was no recurrence at 13-month follow-up. Total removal of these cysts
      and repeated washing of the cavity with 0.9% saline may prevent recurrence and
      aseptic meningitis.

PMID- 19586772
TI  - Giant cell arteritis.
AB  - Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting individuals
      over 50 years of age. It is characterised by granulomatous inflammation that
      affects medium-sized and large arteries. The wide spectrum of clinical
      manifestations can be divided into those related to tissue ischemia from vascular
      lesions and those related to a systemic inflammatory response. The pathogenesis
      of these groups also appears distinct, with vascular lesion formation thought to
      be an adaptive immune response, and the systemic inflammatory reaction an innate
      immune response. Clinical suspicion of GCA must remain especially high in those
      with neurological or visual symptoms and if warranted, prompt treatment with high
      dose corticosteroids is invaluable in halting disease progression.

PMID- 19586773
TI  - Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential
      compound for imaging breast cancer with PET.
AB  - FDG-based imaging with positron emission tomography (PET) has been widely used in
      the detection of cancer, but has not reached its full potential. In breast
      cancer, the glucose/fructose transporter GLUT2 and the fructose transporter GLUT5
      are known to be overexpressed in transformed tissues, implicating that a fructose
      based analogue would be a useful target for the improved imaging of breast
      cancer. We have successfully synthesized the fluorinated fructose compound, 6
      deoxy-6-fluoro-D-fructose (6FDF) and examined its potential for transport and
      accumulation in breast cancer cells. Expression analysis of GLUT isoforms was
      performed on two GLUT5 expressing breast cancer cell lines using western blotting
      and immunocytochemistry. Uptake and inhibition studies were undertaken using
      [14C]-labelled hexoses. Transport inhibition studies showed dose dependent
      inhibition of fructose transport in both cell lines by the newly synthesized 6
      deoxy-6-fluoro-D-fructose (6FDF). Also, near linear uptake over time of [14C]
      labelled 6FDF was observed in both cell lines. It appears that 6FDF may have
      great promise for use in in vivo PET imaging of breast cancer. Ongoing work will
      confirm the efficacy of this compound in imaging in mouse models.

PMID- 19586775
TI  - Anti-listerial activity and structure-activity relationships of the six major
      tyrocidines, cyclic decapeptides from Bacillus aneurinolyticus.
AB  - Six major tyrocidines, purified from the antibiotic tyrothricin complex produced
      by Bacillus aneurinolyticus, showed significant lytic and growth inhibitory
      activity towards the gram+ bacteria, Micrococcus luteus and Listeria
      monocytogenes, but not against the gram- bacterium, Escherichia coli. The
      isolated natural tyrocidines were in particular more active against the leucocin
      A (antimicrobial peptide) resistant strain, L. monocytogenes B73-MR1, than the
      sensitive L. monocytogenes B73 strain. Remarkably similar structure-activity
      trends toward the three gram+ bacteria were found between growth inhibition and
      different physicochemical parameters (solution amphipathicity, theoretical
      lipophilicity, side-chain surface area and mass-over-charge ratio).

PMID- 19586774
TI  - Development of N-[11C]methylamino 4-hydroxy-2(1H)-quinolone derivatives as PET
      radioligands for the glycine-binding site of NMDA receptors.
AB  - In this study, we synthesized and evaluated several amino 4-hydroxy-2(1H)
      quinolone (4HQ) derivatives as new PET radioligand candidates for the glycine
      site of the NMDA receptors. Among these ligands, we discovered that 7-chloro-4
      hydroxy-3-{3-(4-methylaminobenzyl) phenyl}-2-(1H)-quinolone (12) and 5-ethyl-7
      chloro-4-hydroxy-3-(3-methylaminophenyl)-2(1H)-quinolone (32) have high affinity
      for the glycine site (K(i) values; 11.7 nM for 12 and 11.8 nM for 32). In vitro
      autoradiography experiments indicated that [(11)C]12 and [(11)C]32 showed high
      specific binding in the brain slices, which were strongly inhibited by both
      glycine agonists and antagonists. In vivo brain uptake of these (11)C-labeled
      4HQs were examined in normal mice. Cerebellum to blood ratio of accumulation, of
      both [(11)C]12 and [(11)C]32 at 30 min were 0.058, which were slightly higher
      than those of cerebrum to blood ratio (0.043 and 0.042, respectively). These
      results indicated that [(11)C]12 and [(11)C]32 have poor blood brain barrier
      permeability. Although the plasma protein-binding ratio of [(11)C]32 was much
      lower than methoxy analogs (71% vs 94-98%, respectively), [(11)C]32 still binds
      with plasma protein strongly. It is conjectured that still acidic moiety and high
      affinity with plasma protein of [(11)C]32 may prevent in vivo brain uptake. In
      conclusion, [(11)C]12 and [(11)C]32 are unsuitable for imaging cerebral NMDA
      receptors.

PMID- 19586776
TI  - Unfolding the neutron spectrum of a NE213 scintillator using artificial neural
      networks.
AB  - Artificial neural networks technology has been applied to unfold the neutron
      spectra from the pulse height distribution measured with NE213 liquid
      scintillator. Here, both the single and multi-layer perceptron neural network
      models have been implemented to unfold the neutron spectrum from an Am-Be neutron
      source. The activation function and the connectivity of the neurons have been
      investigated and the results have been analyzed in terms of the network's
      performance. The simulation results show that the neural network that utilizes
      the Satlins transfer function has the best performance. In addition, omitting the
      bias connection of the neurons improve the performance of the network. Also, the
      SCINFUL code is used for generating the response functions in the training phase
      of the process. Finally, the results of the neural network simulation have been
      compared with those of the FORIST unfolding code for both (241)Am-Be and (252)Cf
      neutron sources. The results of neural network are in good agreement with FORIST
      code.

PMID- 19586777
TI  - Tessier number 4 bilateral orbito-facial cleft: a 26-year follow-up.
AB  - Orbito-facial number 4 clefts are the rarest craniofacial clefts and only a few
      cases have been reported. We report a case of a complete bilateral Tessier number
      4 cleft, and our approach to surgical correction. We analyse the patient's
      treatment plan over a 26-year follow-up period. We comment on the age at which
      the first surgical procedure is commonly performed with or without a primary bone
      graft, as well as the use of the facial plasty technique with interdigitating Z
      plasty flaps and rotation-transposition flaps. Closure of the cleft can
      constitute an emergency when the patient's globe is exposed.

PMID- 19586778
TI  - Images in cardio-thoracic surgery. Obstructive mass in pulmonary artery.

PMID- 19586779
TI  - Carbon dioxide embolism induced right coronary artery ischaemia during off-pump
      obtuse marginalis artery grafting.
AB  - Although use of carbon dioxide (CO2) blower has been regarded safe during off
      pump coronary bypass surgery (OPCAB), we experienced a case of right coronary
      artery ischaemia induced by retrograde CO2 embolism originating from the opened
      obtuse marginalis artery during OPCAB. The spray pressure can exceed the
      diastolic pressure, especially during grafting at the lateral or posterior wall
      when haemodynamic compromise due to mechanical heart displacement is most severe.
      In this situation, CO2 blowing at an incompletely slinged coronary arteriotomy
      site can result in retrograde migration of CO2 into the ascending aorta causing
      coronary embolism of the right coronary artery. When signs of ischaemia on the
      right coronary artery are encountered during grafting of other coronary artery,
      although CO2 blower has been used, gas embolism should also be considered as the
      cause and identified at the mid-oesophageal aortic valve long-axis view. When
      confirmed, the use of gas blower should immediately be discontinued and coronary
      perfusion pressure increased while allowing time for the CO2 to be absorbed. In
      case of massive embolism, needle aspiration of the gas should also be considered.

PMID- 19586780
TI  - Access and quality of heart failure management programs in Australia.
AB  - BACKGROUND/AIM: In response to the high burden of disease associated with chronic
      heart failure (CHF), in particular the high rates of hospital admissions,
      dedicated CHF management programs (CHF-MP) have been developed. Over the past
      five years there has been a rapid growth of CHF-MPs in Australia. Given the
      apparent mismatch between the demand for, and availability of CHF-MPs, this paper
      has been designed to discuss the accessibility to and quality of current CHF-MPs
      in Australia. METHODS: The data presented in this report has been combined from
      the research of the co-authors, in particular a review of the inequities in
      access to chronic heart failure which utilised geographical information systems
      (GIS) and the survey of heterogeneity in quality and service provision in
      Australian. RESULTS: Of the 62 CHF-MPs surveyed in this study 93% (58) centres
      had been located areas that are rated as Highly Accessible. This result indicated
      that most of the CHF-MPs have been located in capital cities or large regional
      cities. Six percent (4 CHF-MPs) had been located in Accessible areas which were
      country towns or cities. No CHF-MPs had been established outside of cities to
      service the estimated 72,000 individuals with CHF living in rural and remote
      areas. 16% of programs recruited NYHA Class I patients and of these 20% lacked
      confirmation (echocardiogram) of their diagnosis. CONCLUSION: Overall, these data
      highlight the urgent need to provide equitable access to CHF-MP's. When
      establishing CHF-MPs consideration of current evidence based models to ensure
      quality in practice.

PMID- 19586782
TI  - Lamotrigine and twin pregnancy, incidental event or possible correlation?
AB  - Lamotrigine is frequently used to manage epilepsy during pregnancy. However, some
      major and minor birth defects are reported with lamotrigine monotherapy. This
      study is a case series report on 20 epileptic women who were receiving
      lamotrigine in their pregnancy. Apart from the normal pregnancies and births, in
      our study three patients gave birth to healthy twins, two vanished twin syndromes
      occurred and one patient had abortion. Twin pregnancy in association with
      lamotrigine therapy has not been clearly described before. Our observational
      study raises the idea that lamotrigine may induce twin pregnancy but larger
      studies need to investigate the presence or absence of such association more
      decently.

PMID- 19586783
TI  - Drug therapy for improving walking distance in intermittent claudication: a
      systematic review and meta-analysis of robust randomised controlled studies.
AB  - OBJECTIVES: To evaluate the efficacy of pharmacological interventions in
      improving walking capacity and health-related quality of life for people with
      intermittent claudication. DATASOURCES: We searched Medline, EMBASE, Cochrane
      library and relevant websites for studies published from the start of the
      databases to February 2009. In addition, reference lists were manually searched.
      REVIEW METHODS: Based upon a power calculation, only robust (n>56), peer
      reviewed, double-blinded, randomised and placebo-controlled trials were included.
      The main outcomes evaluated were maximal walking distance (MWD) and pain-free
      walking distance on a treadmill. Random models were used in the statistical
      analysis, and chi-square test were used to test for heterogeneity. RESULTS: Among
      220 trials, only 43 trials fulfilled the quality criteria. Treatment periods,
      follow-up and treadmill protocols varied substantially. Vasodilator agents and
      phosphodiesterase inhibitors show robust significant results compared to placebo,
      but the improvements in MWD are modest. The highest benefit was caused by lipid
      lowering agents, which in mean gained above 160 m in MWD, while the other agents
      only improved MWD about 50 m. CONCLUSION: Several drugs have shown to improve
      MWD, but with limited benefits. Statins seem to be the most efficient drug at the
      moment.

PMID- 19586781
TI  - Picolinamidination of phosphopeptides for MALDI-TOF-TOF mass spectrometric
      sequencing with enhanced sensitivity.
AB  - Two orders of magnitude matrix-assisted laser desorption/ionization (MALDI)
      signal enhancement of phosphopeptides has been achieved by picolinamidination of
      N-terminal amine group and epsilon-amine group of lysine residues. Due to the
      presence of picolinamidination tag at the N-terminal amine of peptides, MS/MS
      spectra with a strong b-ion series was obtained, which greatly facilitated
      sequencing and identification of the phosphorylation site. Phosphorylation site
      of a phosphopeptide could be identified from MALDI TOF/TOF spectrum obtained from
      a tryptic or a chymotryptic phosphopeptide, which was not even detected in the
      positive ion mode, without signal enhancement by picolinamidination, due to the
      negative charge of the phosphate group in the presence of other peptides.

PMID- 19586784
TI  - The prognostic value of impaired walking distance on long-term outcome in
      patients with known or suspected peripheral arterial disease.
AB  - OBJECTIVES: To assess the predictive value of walking distance after an exercise
      test on long-term outcome in patients with normal and impaired ankle-brachial
      index (ABI). DESIGN: A total of 2191 patients with known or suspected peripheral
      arterial disease (PAD), who were referred for a single-stage treadmill exercise
      test to diagnose or evaluate their PAD, were enrolled in an observational study
      between 1993 and 2006. MATERIALS AND METHODS: They were divided into two groups:
      normal ABI (>or=0.90) and impaired ABI (<0.90). Walking distance was divided into
      quartiles (no (reference), mild, moderate or severe impairment). RESULTS: In
      patients with normal ABI, severe walking distance was, after adjustment,
      associated with higher mortality risk (hazard ratio (HR): 2.60 (range: 1.16
      5.78)). In patients with impaired ABI, all walking distance impairment quartiles
      were associated with higher mortality (mild HR: 1.26 (range: 0.95-1.67), moderate
      HR: 1.52 (range: 1.13-2.05) and severe HR: 1.69 (range: 1.26-2.27)). Furthermore,
      comparable associations were observed between all walking distance quartiles,
      cardiac death or major adverse cerebrovascular and cardiac events. CONCLUSIONS:
      Our study illustrated that walking impairment is a strong prognostic indicator of
      long-term outcome in patients with impaired and normal ABI, which should be a
      warning sign to physicians to monitor these patients carefully and to provide
      them optimal treatment.

PMID- 19586786
TI  - Serological detection of bovine ephemeral fever virus using an indirect ELISA
      based on antigenic site G1 expressed in Pichia pastoris.
AB  - An indirect ELISA for the serological detection of bovine ephemeral fever virus
      (BEFV) infection in cattle is described in which a glycosylated protein of
      approximately 25 kDa (including the G1 antigenic site of the virus glycoprotein)
      expressed in Pichia pastoris GS115 was used as the coating antigen. The optimal
      concentration of coated antigen was 0.3 microg/well at a serum dilution of 1:40.
      The optimal positive threshold value of the assay was 1.88, as derived from
      receiver operating characteristic curve analysis. The test had 100% sensitivity
      and 96.7% specificity when compared with a micro-neutralisation test using 336
      positive and 180 negative sera to BEFV, respectively. The inter-assay and intra
      assay coefficients of variation for 15 sera were both <5.8% and there was no
      evidence of cross-reactivity between the tested coating antigen and antibodies to
      related rabies virus. The ELISA is an inexpensive and rapid serological detection
      method that would be suitable for screening for BEFV infection on a large scale.

PMID- 19586785
TI  - Development of a model based scoring system for diagnosis of canine disseminated
      intravascular coagulation with independent assessment of sensitivity and
      specificity.
AB  - A template for a scoring system for disseminated intravascular coagulation (DIC)
      in humans has been proposed by the International Society on Thrombosis and
      Haemostasis (ISTH). The objective of this study was to develop and validate a
      similar objective scoring system based on generally available coagulation tests
      for the diagnosis of DIC in dogs. To develop the scoring system, 100 dogs
      consecutively admitted to an intensive care unit (ICU) with diseases predisposing
      for DIC were enrolled prospectively (group A). The validation involved 50 dogs
      consecutively diagnosed with diseases predisposing for DIC, admitted to a
      different ICU (group B). Citrated blood samples were collected daily during
      hospitalisation and diagnosis of DIC was based on the expert evaluation of an
      extended coagulation panel. A multiple logistic regression model was developed in
      group A for DIC diagnosis. The integrity and diagnostic accuracy of the model was
      subsequently evaluated in a separate prospective study at a different ICU (group
      B) and was carried out according to The Standards for Reporting of Diagnostic
      Accuracy (STARD) criteria. Thirty-seven dogs were excluded from group A and four
      from group B due to missing data. Based on expert opinion, 23/63 dogs (37%) had
      DIC. The final multiple logistic regression model was based on activated partial
      thromboplastin time, prothrombin time, D-Dimer and fibrinogen. The model had a
      diagnostic sensitivity and specificity of 90.9% and 90.0%, respectively. The
      diagnostic accuracy of the model was sustained by prospective evaluation in group
      B (sensitivity 83.3%, specificity 77.3%). Based on commonly used, plasma-based
      coagulation assays, it was possible to design an objective diagnostic scoring
      system for canine DIC with a high sensitivity and specificity.

PMID- 19586788
TI  - Vitamin B(12) and birth defects.
AB  - We have reviewed the literature on the effect of vitamin B(12) (cobalamin) on
      development and birth defects. In rodents, administration of antibodies to
      cubilin, a component of the intestinal receptor responsible for cobalamin
      absorption, results in a variety of defects including neural tube defects. There
      is no direct evidence that this is mediated through a direct effect on cobalamin
      metabolism. Homozygosity for inactive versions of the genes for CUBN coding for
      cubilin, AMN, coding for amnionless, the MTR gene coding for methionine synthase,
      or MTRR coding for methionine synthase reductase, is embryonic lethal in mice.
      Homozygosity for a hypomorphic form of the MTRR gene is associated with increased
      occurrence of defects. In man, the following have been associated with neural
      tube defects: decreased maternal serum and amniotic fluid levels of vitamin
      B(12;) decreased serum levels of cobalamin bound to the serum transport protein
      transcobalamin; increased levels of homocysteine and methylmalonic acid; and the
      G allele in mothers and embryos at the 66A>G polymorphism in the MTRR gene. A
      prospective study to determine whether fortification of food with vitamin B(12)
      in addition to folic acid might decrease the incidence of birth defects to a
      greater extent than does fortification with folic acid alone is warranted.

PMID- 19586787
TI  - AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha
      subunit gene causes metabolic remodeling and apoptosis of human liver cancer
      cells.
AB  - Most cancers rely disproportionately on glycolysis for energy even in the
      presence of adequate oxygen supply, a condition known as "aerobic glycolysis", or
      the Warburg effect. Pharmacological reversal of the Warburg effect has been shown
      to cause selective apoptosis of tumor cells, presumably by stimulating
      mitochondrial respiratory chain activity and production of reactive oxygen
      species that, in turn, induce a caspase-mediated series of reactions leading to
      cell death. We reasoned that a similar effect on tumor cells might result from up
      regulation of the E1alpha subunit gene (pda1) of the pyruvate dehydrogenase
      complex (PDC) that catalyzes the rate-limiting step in aerobic glucose oxidation
      and thus plays a major role in the control of oxidative phosphorylation. To test
      this postulate, we employed a self-complementary adeno-associated virus (scAAV)
      based delivery and expression system for targeting pda1 to the mitochondria of
      primary cultures of human hepatoblastoma (HB) and hepatocellular carcinoma (HCC)
      cells. Serotypes 1-10 scAAV vectors that included enhanced green fluorescent
      (egfp) reporter gene driven by either cytomegalovirus (CMV) or chicken beta-actin
      (CBA) promoters were analyzed for transduction ability of HB (Huh-6) and HCC (Huh
      7 and HepG2) cell lines and primary cultures of normal human hepatocytes.
      Serotype 3 scAAV-egfp (scAAV3-egfp) vector was the most efficient and transduced
      up to 90% of cells. We limited the transgene expression primarily to liver cancer
      cells by generating scAAV3 vectors that contained the human alpha-fetoprotein
      promoter (AFP)-driven reporter gene (scAAV3.AFP-egfp) and the potentially
      therapeutic gene scAAV3.AFP-pda1. Infection of Huh-6 cells by the scAAV3.AFP-pda1
      vector increased protein expression of E1alpha, PDC catalytic activity, and late
      stage apoptotic cell death. Apoptosis was also associated with increased protein
      expression of Bcl-X/S, an early marker of apoptosis, and release of cytochrome c
      into the cytosol of infected HB cells. These data indicate that molecular
      targeting of mitochondrial oxidative metabolism in liver cancer cells by AAV3
      mediated delivery of pda1 holds promise as a novel and effective therapeutic
      approach for human hepatic tumors.

PMID- 19586789
TI  - Clinical outcomes of HIV-infected patients hospitalized with bacterial community
      acquired pneumonia.
AB  - BACKGROUND: There are limited and conflicting data on clinical outcomes of
      community-acquired pneumonia (CAP) among HIV-infected patients. METHODS:
      Secondary analyses of clinical outcomes of CAP were performed for 118 patients
      with HIV infection and 2790 patients without HIV infection enrolled in the
      Community-Acquired Pneumonia Organization (CAPO) international study. After
      adjustment for significant confounders, the effect of HIV infection on length of
      stay (LOS) and time to clinical stability (TCS) were examined by survival
      analyses and overall mortality and CAP-related mortality by logistic regression
      methods. RESULTS: After adjusting for significant confounders, hospitalized HIV
      infected patients with CAP did not have longer times to reach clinical stability
      (HR 1.126; 95% CI 0.917-1.391; p=0.251) or longer stays in the hospital (HR
      1.191, 95% CI 0.979-1.449; p=0.080). In addition, HIV infection did not
      significantly influence overall mortality rates (OR 1.205, 95% CI 0.686-2.116;
      p=0.517) or CAP-related mortality rates (OR 1.338; 95% CI 0.623-3.725; p=0.355).
      CONCLUSION: The presence of HIV infection did not influence the clinical outcomes
      of CAP among patients assessed at CAPO centers. It is not intended that our
      results be extrapolated to populations receiving limited healthcare for advanced
      HIV disease, malnourishment and parasitic diseases.

PMID- 19586790
TI  - The comparison of phonophoresis, iontophoresis and local steroid injection in
      carpal tunnel syndrome treatment.

PMID- 19586791
TI  - [Female genital mutilation: have you been dealing with them?].

PMID- 19586792
TI  - [Fetal ultrasonography and Doppler in isolated congenital heart block].
AB  - Isolated congenital heart block is linked to transplacental passage of maternal
      anti-SSA/Ro and/or anti-SSB/La antibodies that may be related to a connective
      tissue disease. Ultrasonography and Doppler are essential to screen fetus at
      risk. They allow the diagnosis of first- and second-degree blocks which are
      probably preliminary stages in conducting tissue's injury. In these situations, a
      maternal treatment by fluorinated steroids can be proposed because of its
      possible effect on partial blocks. However, these early signs of nodal injury can
      be lacking: some fetus present a complete heart block without previously detected
      less advanced block. Moreover, the significance of first-degree block is unclear
      since it could reverse spontaneously. Other markers of nodal injury would be
      valuable. In case of complete congenital heart block, ultrasonography is useful
      to detect congestive heart failure and help the obstetrical management when
      unfavorable prognostic signs occur.

PMID- 19586793
TI  - Confocal microscopy indentation system for studying in situ chondrocyte
      mechanics.
AB  - Chondrocytes synthesize extracellular matrix molecules, thus they are essential
      for the development, adaptation and maintenance of articular cartilage.
      Furthermore, it is well accepted that the biosynthetic activity of chondrocytes
      is influenced by the mechanical environment. Therefore, their response to
      mechanical stimuli has been studied extensively. Much of the knowledge in this
      area of research has been derived from testing of isolated cells, cartilage
      explants, and fixed cartilage specimens: systems that differ in important aspects
      from chondrocytes embedded in articular cartilage and observed during loading
      conditions. In this study, current model systems have been improved by working
      with the intact cartilage in real time. An indentation system was designed on a
      confocal microscope that allows for simultaneous loading and observation of
      chondrocytes in their native environment. Cell mechanics were then measured under
      precisely controlled loading conditions. The indentation system is based on a
      light transmissible cylindrical glass indentor of 0.17 mm thickness and 1.64 mm
      diameter that is aligned along the focal axis of the microscope and allows for
      real time observation of live cells in their native environment. The system can
      be used to study cell deformation and biological responses, such as calcium
      sparks, while applying prescribed loads on the cartilage surface. It can also
      provide novel information on the relationship between cell loading and cartilage
      adaptive/degenerative processes in the intact tissue.

PMID- 19586794
TI  - Optimal real-time Q-ball imaging using regularized Kalman filtering with
      incremental orientation sets.
AB  - Diffusion MRI has become an established research tool for the investigation of
      tissue structure and orientation. Since its inception, Diffusion MRI has expanded
      considerably to include a number of variations such as diffusion tensor imaging
      (DTI), diffusion spectrum imaging (DSI) and Q-ball imaging (QBI). The acquisition
      and analysis of such data is very challenging due to its complexity. Recently, an
      exciting new Kalman filtering framework has been proposed for DTI and QBI
      reconstructions in real-time during the repetition time (TR) of the acquisition
      sequence. In this article, we first revisit and thoroughly analyze this approach
      and show it is actually sub-optimal and not recursively minimizing the intended
      criterion due to the Laplace-Beltrami regularization term. Then, we propose a new
      approach that implements the QBI reconstruction algorithm in real-time using a
      fast and robust Laplace-Beltrami regularization without sacrificing the
      optimality of the Kalman filter. We demonstrate that our method solves the
      correct minimization problem at each iteration and recursively provides the
      optimal QBI solution. We validate with real QBI data that our proposed real-time
      method is equivalent in terms of QBI estimation accuracy to the standard offline
      processing techniques and outperforms the existing solution. Last, we propose a
      fast algorithm to recursively compute gradient orientation sets whose partial
      subsets are almost uniform and show that it can also be applied to the problem of
      efficiently ordering an existing point-set of any size. This work enables a
      clinician to start an acquisition with just the minimum number of gradient
      directions and an initial estimate of the orientation distribution functions
      (ODF) and then the next gradient directions and ODF estimates can be recursively
      and optimally determined, allowing the acquisition to be stopped as soon as
      desired or at any iteration with the optimal ODF estimates. This opens new and
      interesting opportunities for real-time feedback for clinicians during an
      acquisition and also for researchers investigating into optimal diffusion
      orientation sets and real-time fiber tracking and connectivity mapping.

PMID- 19586796
TI  - Spectrophotometric determination of perphenazine with the detection system of
      potassium ferricyanide-Fe(III) in pharmaceutical and serum samples.
AB  - In this paper, a novel spectrophotometric method has been established to
      determine perphenazine using the detection system of potassium ferricyanide
      Fe(III). In the presence of potassium ferricyanide, it has been demonstrated that
      Fe(III) is reduced to Fe(II) by perphenazine at pH 4.0. In addition, soluble
      prussian blue (KFe(III)[Fe(II)(CN)(6)]) is produced by the reaction between the
      in situ formed Fe(II) and potassium ferricyanide. The absorbance of soluble
      prussian blue is measured at the absorption maximum of 735 nm, and the amount of
      perphenazine can be calculated based on this absorbance. The absorbance is linear
      to perphenazine concentration in the ranges of 0.05-25.00 microg/mL with
      correlation coefficients of 0.9997, and the linear regression equation is A =
      0.0069 + 0.1285C (microg/mL). The detection limit (3sigma/k) is 0.049 microg/mL,
      and the relative standard deviation (R.S.D.) is 0.86% (n = 11). Moreover, the
      apparent molar absorption coefficient of indirect determination of perphenazine
      is 5.2 x 10(4) L/mol cm. The parameters with regard to determination are
      optimized, and the reaction mechanism is discussed. This method has been
      successfully applied to the determination of perphenazine in pharmaceutical and
      serum samples. Analytical results obtained with this novel assay are
      satisfactory.

PMID- 19586795
TI  - Factors associated with clinical benefit from epidermal growth factor receptor
      inhibitors in recurrent and metastatic squamous cell carcinoma of the head and
      neck.
AB  - Single agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKI) have demonstrated reproducible response rates of 5-15% in treatment of
      squamous cell carcinomas of the head and neck (SCCHN). The subset of patients
      that benefits most from these agents remains unknown. We reviewed individual
      patient data from five clinical trials of erlotinib, lapatinib, or gefitinib to
      determine if there are clinical characteristics that are associated with clinical
      benefit defined as complete response (CR), partial response (PR), and stable
      disease (SD) >4months. Secondary endpoints included progression-free survival
      (PFS) and overall survival (OS). Three-hundred and nineteen subjects were
      included. Observed responses were: 1% CR, 6% PR, 24% SD >4months, 18% SD
      <4months, 45% progressive disease (PD), 7% not evaluable (NE). The median OS was
      6.4months and the median PFS was 2.7months. The most common toxicities observed
      were rash (grade 1 in 37%, grade 2 in 33%, grade 3+ in 6%) and diarrhea (grade 1
      in 30%, grade 2 in 10%, grade 3+ in 5%). Performance status (PS) (p=0.04), older
      age (p=0.02), and development of rash (p<0.01), diarrhea (p=0.03), or oral side
      effects (p=0.02) were independently associated with clinical benefit. Older age,
      better PS, and development of rash were associated with longer PFS and OS.
      Clinical parameters that appear to predict response to EGFR TKI include PS and
      age. EGFR mechanistic toxicities that develop during therapy are also highly
      associated with benefit and suggest a relationship between drug exposure and
      outcome.

PMID- 19586797
TI  - Health risks of the occupational exposure to microbiological and chemical
      pollutants in a municipal waste organic fraction treatment plant.
AB  - Composting is a good alternative for the treatment of organic waste. However, an
      important amount of hazardous agents such as bioaerosols and volatile organic
      compounds may be released during the process. Therefore, the presence of
      microbiological and chemical pollutants emitted to air may mean a risk for the
      health of composting plants workers. We here report the results of an
      investigation aimed at evaluating the occupational exposure to chemical and
      biological agents for workers of an organic waste treatment facility (Montcada i
      Reixac, Catalonia, Spain). Total concentrations of bacteria and fungi (at 25
      degrees C and 37 degrees C), including Aspergillus fumigatus, were determined on
      a 3-month basis in 4 areas of the composting plant (reception, sorting,
      composting and cogeneration halls). Non-cancer and cancer risks were assessed.
      Workers in the sorting cabins seemed to be the most exposed to pollutants.
      Consequently, the use of preventive measures, such as integrated P3 filter masks
      and gloves are highly recommended. On the other hand, the emission and dispersion
      of bioaerosols and particles should be minimized during the process through the
      application of additional measures, such as the humectation of waste and the
      installation of biofilters. The results of this study can be useful to elaborate
      occupational risk prevention programs for workers in composting plants.

PMID- 19586798
TI  - A systematic review on the effectiveness of external ankle supports in the
      prevention of inversion ankle sprains among elite and recreational players.
AB  - Epidemiological studies have shown that 10-28% of all sports injuries are ankle
      sprains, leading to the longest absence from athletic activity compared to other
      types of injuries. This study was conducted to evaluate the effectiveness of
      external ankle supports in the prevention of inversion ankle sprains and identify
      which type of ankle support was superior to the other. A search strategy was
      developed, using the keywords, ankle supports, ankle brace, ankle tapes, ankle
      sprains and athletes, to identify available literature in the databases (MEDLINE,
      PubMed, CINAHL, EMBASE, etc.), libraries and unpublished papers. Trials which
      consider adolescents and adults, elite and recreational players as participants
      were the study of choice. External ankle supports comprise ankle tape, brace or
      orthosis applied to the ankle to prevent ankle sprains. The main outcome measures
      were frequency of ankle sprains. Two reviewers assessed the quality of the
      studies included using the Joanna Briggs Institute (JBI Appraisal tool). Whenever
      possible, results were statistically pooled and interpreted. A total of seven
      trials were finally included in this study. The studies included were of moderate
      quality, with blinding as the hardest criteria to fulfill. The main significant
      finding was the reduction of ankle sprain by 69% (OR 0.31, 95% CI 0.18-0.51) with
      the use of ankle brace and reduction of ankle sprain by 71% (OR 0.29, 95% CI 0.14
      0.57) with the use of ankle tape among previously injured athletes. No type of
      ankle support was found to be superior than the other.

PMID- 19586799
TI  - At sea with SEAS: the first clinical endpoint trial for ezetimibe, treatment of
      patients with mild to moderate aortic stenosis, ends with mixed results and more
      controversy.
AB  - SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) hypothesised that aggressive
      lipid lowering with simvastatin/ezetimibe reduced cardiovascular disease (CVD)
      risk and the need for aortic valve replacement (AVR) in patients with
      asymptomatic aortic stenosis (AS). The study enrolled from 173 centres in seven
      European countries 1873 elderly non-diabetics with mild to moderate AS (mean
      aortic-valve area 1.28+/-0.47 cm(2)), who had no indication for lipid-lowering
      therapy. Patients were randomised to treatment with either simvastatin/ezetimibe
      40/10mg daily or matching placebo after a four-week diet/placebo run-in period.
      Compared with placebo, LDL cholesterol was reduced by 61% (2.0 mmol/l). There was
      no difference in the primary endpoint (a combination of AVR, CV death, non-fatal
      MI, congestive heart failure from AS progression, coronary revascularisation,
      hospitalised unstable angina and non-haemorrhagic stroke). Compared with placebo,
      CVD events were reduced by 4.4% from 20.1% to 15.7% in the simvastatin/ezetimibe
      group (p=0.02). Cancer incidence and cancer deaths were more frequent in the
      simvastatin/ezetimibe group (9.9% vs. 7.0%, p=0.03 and 4.1% vs. 2.5%, p=0.05,
      respectively). These differences were not related to any form of cancer and did
      not increase with increased duration of therapy.

PMID- 19586800
TI  - Safety and efficacy of sunitinib in patients with advanced hepatocellular
      carcinoma: an open-label, multicentre, phase II study.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) tumour spread is partly dependent on
      neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe
      and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti
      angiogenic properties, was assessed in patients with advanced unresectable HCC.
      METHODS: Between February and July, 2006, eligible patients were enrolled and
      treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed
      by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II
      trial was objective response rate according to Response Evaluation Criteria in
      Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This
      trial is registered with ClinicalTrials.gov, number NCT00247676. FINDINGS: Of 37
      patients enrolled, one (2.7%) patient experienced a confirmed partial response,
      giving an overall objective response rate of 2.7% (95% CI 0.1-14.2); on the basis
      of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients
      achieved stable disease for over 3 months. Commonly observed grade 3 and 4
      adverse events included thrombocytopenia (14 of 37; 37.8%), neutropenia (nine of
      37; 24.3%), asthenia (five of 37; 13.5%), hand-foot syndrome (four of 37; 10.8%),
      and anaemia (four of 37; 10.8%). There were four deaths among the 37 patients
      (10.8%) that were possibly related to treatment. INTERPRETATION: Sunitinib showed
      pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC.
      The response rate was low, and the study did not meet the primary endpoint based
      on RECIST criteria. FUNDING: Pfizer Oncology.

PMID- 19586801
TI  - Immunoregulatory effects of HO-1: how does it work?
AB  - The heme-catabolizing enzyme heme oxygenase-1 (HO-1; encoded by the Hmox1 gene)
      inhibits the pathogenesis of several immune-mediated inflammatory diseases. This
      unusually broad salutary effect is thought to rely on the immunoregulatory
      actions of HO-1, exerted on innate and adaptive immune cells. According to this
      notion, HO-1 'dampens' innate and adaptive immune responses, limiting immune
      mediated tissue injury and thus suppressing the pathogenesis of immune-mediated
      inflammatory diseases. We will argue that the salutary effects of HO-1 are also
      exerted via its cytoprotective action, which sustains tissue function and
      prevents unfettered immune activation by endogenous proinflammatory ligands
      released from injured cells.

PMID- 19586802
TI  - Commentary to "Outcome of complete primary bladder exstrophy repair: single
      center experience".

PMID- 19586803
TI  - Refined characterization and reference values of the pediatric T- and B-cell
      compartments.
AB  - Work in the past years has led to a refined phenotypical description of
      functionally distinct T- and B-cell subsets. Since both lymphocyte compartments
      are established and undergo dramatic changes during childhood, redefined
      pediatric reference values of both compartments are needed. In a cohort of 145
      healthy children, aged 0-18 years, the relative and absolute numbers of the
      various T- and B-cell subsets were determined. In addition, we found that besides
      thymic output, naive (CD27(+)CD45RO(-)) T-cell proliferation contributed
      significantly to the establishment of the naive T-cell compartment. At birth,
      regulatory (CD25(+)CD127(-)CD4(+)) T cells (Tregs) mainly had a naive
      (CD27(+)CD45RO(-)) phenotype whereas 'memory or effector-like' (CD45RO(+)) Tregs
      accumulated slowly during childhood. Besides the CD27(+)IgM(+)IgD(+) memory B
      cell population, the recently identified CD27(-)IgG(+) and CD27(-)IgA(+) memory B
      cell populations were already present at birth. These data provide reference
      values of the T- and B-cell compartments during childhood for studies of
      immunological disorders or immune reconstitution in children.

PMID- 19586805
TI  - Chronic pancreatitis in Italy.

PMID- 19586806
TI  - Optimal technique for microvascular anastomosis of very small vessels:
      Comparative study of three techniques in a rat superficial inferior epigastric
      arterial flap model.
AB  - OBJECTIVE: The anastomosis of very small vessels (external diameter: < or =
      0.5mm) is challenging and requires high microsurgical skill. This study aims to
      investigate the optimal technique for the anastomosis of very small vessels. We
      compared three anastomotic techniques on the basis of success rate and
      anastomosis time in a superficial inferior epigastric arterial flap model in
      rats. METHODS: Forty-five Sprague-Dawley rats were divided into three groups of
      15 rats. The superficial inferior epigastric artery flap was elevated, and only
      the artery was cut and anastomosed under magnification. The anastomosis was
      performed with the conventional technique, with the intravascular stenting
      technique or with the open guide suture technique. Flap survival was assessed on
      postoperative day 5, and the success rates of the groups were compared. In
      addition, the time required for anastomosis was compared between the groups.
      RESULTS: All flaps survived, and success rates did not differ significantly
      between the groups. The average anastomosis times with the conventional technique
      (770.0s) and the intravascular stenting technique (822.8s) did not differ
      significantly but were significantly greater than that with the open guide suture
      technique (699.2s). CONCLUSION: The open guide suture technique simplifies
      anastomosis and can be recommended as a new standard technique for the
      anastomosis of very small vessels. Furthermore, the benefit of the intravascular
      stenting technique is minimal for either skilled or unskilled microsurgeons.

PMID- 19586804
TI  - Determination of D-serine and D-alanine in the tissues and physiological fluids
      of mice with various D-amino-acid oxidase activities using two-dimensional high
      performance liquid chromatography with fluorescence detection.
AB  - Two-dimensional-HPLC procedures have been established for the sensitive and
      selective determination of D-serine (D-Ser) and D-alanine (D-Ala), and their
      amounts in the tissues and physiological fluids of mice with various D-amino-acid
      oxidase (DAO) activities have been demonstrated. These two D-amino acids are
      modulators of the N-methyl-D-aspartate receptor mediated neurotransmission, and
      the alterations in their amounts following the changes in the DAO activity are
      matters of interest. After pre-column derivatization with 4-fluoro-7-nitro-2,1,3
      benzoxadiazole (NBD-F), the D-amino acids were determined by the 2D-HPLC system
      with fluorescence detectors. As the first dimension, a microbore-monolithic-ODS
      column (750 mm x 0.53 mm I.D.) was adopted and a self-packed narrowbore-Pirkle
      type enantioselective column (Sumichiral OA-2500S, 250 mm x 1.5 mm I.D.) was
      selected for the second dimension. The lower limits of quantitation of D-Ser and
      D-Ala were 500 amol, and the within-day and day-to-day precisions were less than
      6.8%. Using these methods, the amounts of D-Ser and D-Ala in 6 brain tissues, 4
      peripheral tissues, serum and urine of mice having various DAO activities were
      determined; the amounts of these D-amino acids were drastically increased with a
      lowering of the DAO activity except for the cases of D-Ser in the frontal brain
      regions. The present micro-2D-HPLC procedures are powerful tools for the
      determination of small amounts of D-Ser and D-Ala in mammalian samples, and the
      obtained results would be useful for developing novel drugs that modulate the DAO
      activity, such as DAO inhibitors, against neuronal diseases.

PMID- 19586807
TI  - Relationships between prenatal smoking cessation, gestational weight gain and
      maternal lifestyle characteristics.
AB  - OBJECTIVES: To describe maternal characteristics and lifestyle factors associated
      with prenatal smoking habits and to appraise the effect of quitting smoking in
      early gestation on maternal weight gain during pregnancy. METHODS: This is a
      follow-up study of 1753 women who gave birth in 1984/1985 in Stockholm, Sweden.
      Multivariate logistic models were used to evaluate the association between
      smoking cessation and weight gain above the American Institute of Medicine (IOM)
      recommendations, based on pre-pregnancy BMI. RESULTS: About 22% of all
      participants identified themselves as current smokers and 11.6% reported smoking
      cessation during pregnancy. Smokers were more likely to be single mothers and
      reported low quality of breakfast (e.g. eating only 1 food group at breakfast).
      Non-smokers were older, more likely to be married and have a healthier lifestyle.
      Quitters also adopted healthier eating habits (e.g. improvement in their
      breakfast quality). Women who quit smoking gained, on average, 15.3 kg (SD 4.4)
      during pregnancy, non-smokers gained 14.1 kg (SD 4.0) and smokers gained 13.8 kg
      (SD 4.3). Quitters gained significantly more weight than both non-smokers and
      smokers (p<0.001). Smoking cessation was significantly associated with gaining
      weight above IOM recommendations, even after controlling for potential
      confounders (OR: 2.0; 95%CI: 1.4-3.0; p<or=0.0001). CONCLUSIONS: In this
      population, smoking cessation in early pregnancy doubled the likelihood of
      gaining excess weight. This finding highlights the need for supportive measures
      to help control weight gain among women who quit smoking during pregnancy.

PMID- 19586808
TI  - Governing stem cell banks and registries: emerging issues.
AB  - The expansion of national and international research efforts in stem cell
      research is increasingly paired with the trend of establishing stem cell banks
      and registries. In jurisdictions crossing the spectrum of restrictive to liberal
      stem cell policies, banks and registries are emerging as an essential resource
      for transnational access to quality-controlled and ethically sourced stem cell
      lines. In this study, we report the preliminary findings of a survey of stem cell
      banks participating in the International Stem Cell Forum's International Stem
      Cell Banking Initiative (ISCBI). The questionnaire circulated to all ISCBI
      members addressed both general issues surrounding research policies (e.g.,
      national policies regulating the permissibility of conducting embryonic stem cell
      research (hESCR)) and, more specifically, issues relating to the governance of
      stem cell banking projects. The results of the questionnaire were complemented by
      scholarly research conducted by the authors. This article provides an overview of
      the current international hESC banking landscape (I). For this purpose, the
      policy and governance approaches adopted in the surveyed stem cell banks at the
      national level will be analyzed and areas of convergence and variance will be
      identified (II). It is beyond the scope of this paper to provide a comprehensive
      analysis of the wide range of possible governance approaches, policy responses,
      and their implications. However, we want to provide a starting point for
      discussion surrounding key questions and challenges as concerns provenance,
      access, and deposit of hESC lines (III). Finally, while our analysis is focused
      on research grade hESCs, the lessons to be gleaned from this examination will
      encourage further thought, analysis, and research into the issues raised in the
      banking and governance of other sources of stem cell lines (e.g., SCNT,
      parthenogenesis, iPs) (IV).

PMID- 19586809
TI  - Muscle fatty infiltration in rotator cuff tears: descriptive analysis of 1688
      cases.
AB  - INTRODUCTION: Fatty infiltration (FI) is an important prognosis factor in the
      anatomical and functional outcomes of rotator cuff repairs. The objective of this
      study was to analyze the natural history of muscle FI and better evaluate its
      onset and aggravation time frame. MATERIAL AND METHODS: A total of 1688 medical
      charts of patients operated on for rotator cuff tear and with a preoperative CT
      arthrogram (82%) or an MRI (18%) were reviewed. Surgery was performed between
      1988 and 2005. The FI of each muscle was assessed as minimal (in Goutallier's
      stages 0 and 1), intermediate (in stage 2), and severe (in stages 3 and 4).
      Regarding supraspinatus, we retained the mean FI observed in the sagittal,
      coronal, and axial planes; for the infraspinatus and the subscapularis, we
      retained the observed mean on two views at the upper and lower levels of the
      glenoid in the axial plane. RESULTS: We found a statistically significant
      correlation (p<0.0005) between FI, the type of tendon lesion, and patient age for
      the supraspinatus, the infraspinatus, and the subscapularis. Statistically, the
      FI significantly increased (p<0.0005) with time elapsed for the supraspinatus and
      the infraspinatus but not significantly for the subscapularis. The mean time to
      tendon rupture observed for intermediate FI was three years for the supraspinatus
      and 2.5 years for the infraspinatus and the subscapularis when their tendons
      ruptured. The mean time observed to severe FI was five, four, and three years for
      the supraspinatus, the infraspinatus, and the subscapularis, respectively.
      DISCUSSION AND CONCLUSION: The more extensive the lesion, the longer the time
      following rupture, and the older the patient is, the more severe the FI is. The
      objective of surgery is to intervene before intermediate FI sets in, which means
      irreversible functional loss. LEVEL OF EVIDENCE: Level IV. Diagnostic
      Retrospective Study.

PMID- 19586810
TI  - Guest editorial: introduction to the special section on biomedical informatics.

PMID- 19586811
TI  - Complementary DNA microarray image processing based on the fuzzy gaussian mixture
      model.
AB  - The objective of this paper was to investigate the segmentation ability of the
      fuzzy Gaussian mixture model (FGMM) clustering algorithm, applied on
      complementary DNA (cDNA) images. Following a standard established procedure, a
      simulated microarray image of 1600 cells, each containing one spot, was produced.
      For further evaluation of the algorithm, three real microarray images were also
      used, each containing 6400 spots. For the task of locating spot borders and
      surrounding background (BG) in each cell, an automatic gridding process was
      developed and applied on microarray images. The FGMM and the Gaussian mixture
      model (GMM) algorithms were applied to each cell with the purpose of
      discriminating foreground (FG) from BG. The segmentation abilities of both
      algorithms were evaluated by means of the segmentation matching factor,
      coefficient of determination, and concordance correlation, in respect to the
      actual classes (FG-BG pixels) of the simulated spots. Pairwise correlation and
      mean absolute error of the real images among replicates were also calculated. The
      FGMM was found to perform better and with equal processing time, as compared to
      the GMM, rendering the FGMM algorithm an efficient alternative for segmenting
      cDNA microarray images.

PMID- 19586812
TI  - Wavelet-based compression with ROI coding support for mobile access to DICOM
      images over heterogeneous radio networks.
AB  - Most of the commercial medical image viewers do not provide scalability in image
      compression and/or region of interest (ROI) encoding/decoding. Furthermore, these
      viewers do not take into consideration the special requirements and needs of a
      heterogeneous radio setting that is constituted by different access technologies
      [e.g., general packet radio services (GPRS)/ universal mobile telecommunications
      system (UMTS), wireless local area network (WLAN), and digital video broadcasting
      (DVB-H)]. This paper discusses a medical application that contains a viewer for
      digital imaging and communications in medicine (DICOM) images as a core module.
      The proposed application enables scalable wavelet-based compression, retrieval,
      and decompression of DICOM medical images and also supports ROI coding/decoding.
      Furthermore, the presented application is appropriate for use by mobile devices
      activating in heterogeneous radio settings. In this context, performance issues
      regarding the usage of the proposed application in the case of a prototype
      heterogeneous system setup are also discussed.

PMID- 19586813
TI  - Achieving clinical statement interoperability using R-MIM and archetype-based
      semantic transformations.
AB  - Effective use of electronic healthcare records (EHRs) has the potential to
      positively influence both the quality and the cost of health care. Consequently,
      sharing patient's EHRs is becoming a global priority in the healthcare
      information technology domain. This paper addresses the interoperability of EHR
      structure and content. It describes how two different EHR standards derived from
      the same reference information model (RIM) can be mapped to each other by using
      archetypes, refined message information model (R-MIM) derivations, and semantic
      tools. It is also demonstrated that well-defined R-MIM derivation rules help
      tracing the class properties back to their origins when the R-MIMs of two EHR
      standards are derived from the same RIM. Using well-defined rules also enable
      finding equivalences in the properties of the source and target EHRs. Yet an R
      MIM still defines the concepts at the generic level. Archetypes (or templates),
      on the other hand, constrain an R-MIM to domain-specific concepts, and hence,
      provide finer granularity semantics. Therefore, while mapping clinical statements
      between EHRs, we also make use of the archetype semantics. Derivation statements
      are inferred from the Web Ontology Language definitions of the RIM, the R-MIMs,
      and the archetypes. Finally, we show how to transform Health Level Seven clinical
      statement instances to EHRcom clinical statement instances and vice versa by
      using the generated mapping definitions.

PMID- 19586814
TI  - A computational-intelligence-based approach for detection of exudates in diabetic
      retinopathy images.
AB  - Currently, there is an increasing interest for setting up medical systems that
      can screen a large number of people for sight threatening diseases, such as
      diabetic retinopathy. This paper presents a method for automated identification
      of exudate pathologies in retinopathy images based on computational intelligence
      techniques. The color retinal images are segmented using fuzzy c-means clustering
      following some preprocessing steps, i.e., color normalization and contrast
      enhancement. The entire segmented images establish a dataset of regions. To
      classify these segmented regions into exudates and nonexudates, a set of initial
      features such as color, size, edge strength, and texture are extracted. A genetic
      based algorithm is used to rank the features and identify the subset that gives
      the best classification results. The selected feature vectors are then classified
      using a multilayer neural network classifier. The algorithm was implemented using
      a large image dataset consisting of 300 manually labeled retinal images, and
      could identify affected retinal images with 96.0% sensitivity while it recognized
      94.6% of the normal images, i.e., the specificity. Moreover, the proposed scheme
      illustrated an accuracy including 93.5% sensitivity and 92.1% predictivity for
      identification of retinal exudates at the pixel level.

PMID- 19586815
TI  - Image denoising using trivariate shrinkage filter in the wavelet domain and joint
      bilateral filter in the spatial domain.
AB  - This correspondence proposes an efficient algorithm for removing Gaussian noise
      from corrupted image by incorporating a wavelet-based trivariate shrinkage filter
      with a spatial-based joint bilateral filter. In the wavelet domain, the wavelet
      coefficients are modeled as trivariate Gaussian distribution, taking into account
      the statistical dependencies among intrascale wavelet coefficients, and then a
      trivariate shrinkage filter is derived by using the maximum a posteriori (MAP)
      estimator. Although wavelet-based methods are efficient in image denoising, they
      are prone to producing salient artifacts such as low-frequency noise and edge
      ringing which relate to the structure of the underlying wavelet. On the other
      hand, most spatial-based algorithms output much higher quality denoising image
      with less artifacts. However, they are usually too computationally demanding. In
      order to reduce the computational cost, we develop an efficient joint bilateral
      filter by using the wavelet denoising result rather than directly processing the
      noisy image in the spatial domain. This filter could suppress the noise while
      preserve image details with small computational cost. Extension to color image
      denoising is also presented. We compare our denoising algorithm with other
      denoising techniques in terms of PSNR and visual quality. The experimental
      results indicate that our algorithm is competitive with other denoising
      techniques.

PMID- 19586817
TI  - Exploiting inherent parallelisms for accelerating linear Hough transform.
AB  - Accelerating Hough transform in hardware has been of interest due its popularity
      in real-time capable image processing applications. In most existing linear Hough
      transform architectures, an m xm edge map is serially read for processing,
      resulting in a total computation time of at least m(2) cycles. In this paper, we
      propose a novel parallel Hough transform computation method called the Additive
      Hough transform (AHT), wherein the image is divided using a k x k grid to reduce
      the total computation time by a factor of k(2). We have also proposed an
      efficient implementation of the AHT consisting of a look-up table (LUT) and two
      operand adder arrays for every angle. Techniques to condense the LUT size have
      also been proposed to further reduce area utilization by as much as 50%. Our
      investigations based on employing an 8 x 8 grid shows a 1000 x speedup compared
      to existing architectures for a range of image sizes. Area-time trade-off
      analysis has been presented to demonstrate that the area-time product of the
      proposed AHT-based implementation is at least 43% lower than other
      implementations reported in the literature. We have also included and
      characterized a hierarchical addition step in order to generate a global
      accumulation space equivalent to that of the conventional HT. It is shown that
      the proposed implementation with the hierarchical addition step remains superior
      to other methods in terms of both performance and area-time product metrics.
      Finally, we show that the proposed solution is equally efficient when applied on
      rectangular images.

PMID- 19586816
TI  - Tricolor attenuation model for shadow detection.
AB  - Shadows, the common phenomena in most outdoor scenes, bring many problems in
      image processing and computer vision. In this paper, we present a novel method
      focusing on extracting shadows from a single outdoor image. The proposed tricolor
      attenuation model (TAM) that describe the attenuation relationship between shadow
      and its nonshadow background is derived based on image formation theory. The
      parameters of the TAM are fixed by using the spectral power distribution (SPD) of
      daylight and skylight, which are estimated according to Planck's blackbody
      irradiance law. Based on the TAM, a multistep shadow detection algorithm is
      proposed to extract shadows. Compared with previous methods, the algorithm can be
      applied to process single images gotten in real complex scenes without prior
      knowledge. The experimental results validate the performance of the model.

PMID- 19586818
TI  - Color image segmentation by the vector-valued Allen-Cahn phase-field model: a
      multigrid solution.
AB  - We present an efficient numerical solution of a PDE-driven model for color image
      segmentation and give numerical examples of the results. The method combines the
      vector-valued Allen-Cahn phase field equation with initial data fitting terms
      with prescribed interface width and fidelity constants. Efficient numerical
      solution is achieved using a multigrid splitting of a finite element space,
      thereby producing an efficient and robust method for the segmentation of large
      images. We also present the use of adaptive mesh refinement to further speed up
      the segmentation process.

PMID- 19586819
TI  - Video condensation by ribbon carving.
AB  - Efficient browsing of long video sequences is a key tool in visual surveillance,
      e.g., for postevent video forensics, but can also be used for fast review of
      motion pictures and home videos. While frame skipping (fixed or adaptive) is
      straightforward to implement, its performance is quite limited. Although more
      efficient techniques have been developed, such as video summarization and video
      montage, they lose either the temporal or semantic context of events. A recently
      proposed method called video synopsis deals with some of these issues but
      involves multiple processing stages and is fairly complex. Video condensation,
      that we propose here, is novel in the way information is removed from the space
      time video volume, is conceptually simple and relatively easy to implement. We
      introduce the concept of a video ribbon inspired by that of a seam recently
      proposed for image resizing. We recursively carve ribbons out by minimizing an
      activity-aware cost function using dynamic programming. The ribbon model we
      develop is flexible and permits an easy adjustment of the compromise between
      temporal condensation ratio and anachronism of events. We also propose sliding
      window ribbon carving to handle streaming video and demonstrate the method's
      efficiency on motor and pedestrian traffic data.

PMID- 19586820
TI  - Channel coding for progressive images in a 2-D time-frequency OFDM block with
      channel estimation errors.
AB  - Coding and diversity are very effective techniques for improving transmission
      reliability in a mobile wireless environment. The use of diversity is
      particularly important for multimedia communications over fading channels. In
      this work, we study the transmission of progressive image bitstreams using
      channel coding in a 2-D time-frequency resource block in an OFDM network,
      employing time and frequency diversities simultaneously. In particular, in the
      frequency domain, based on the order of diversity and the correlation of
      individual subcarriers, we construct symmetric n -channel FEC-based multiple
      descriptions using channel erasure codes combined with embedded image coding. In
      the time domain, a concatenation of RCPC codes and CRC codes is employed to
      protect individual descriptions. We consider the physical channel conditions
      arising from various coherence bandwidths and coherence times, leading to a range
      of orders of diversities available in the time and frequency domains. We
      investigate the effects of different error patterns on the delivered image
      quality due to various fade rates. We also study the tradeoffs and compare the
      relative effectiveness associated with the use of erasure codes in the frequency
      domain and convolutional codes in the time domain under different physical
      environments. Both the effects of intercarrier interference and channel
      estimation errors are included in our study. Specifically, the effects of channel
      estimation errors, frequency selectivity and the rate of the channel variations
      are taken into consideration for the construction of the 2-D time-frequency
      block. We provide results showing the gain that the proposed model achieves
      compared to a system without temporal coding. In one example, for a system
      experiencing flat fading, low Doppler, and imperfect CSI, we find that the
      increase in PSNR compared to a system without time diversity is as much as 9.4
      dB.

PMID- 19586821
TI  - Vector lifting schemes for stereo image coding.
AB  - Many research efforts have been devoted to the improvement of stereo image coding
      techniques for storage or transmission. In this paper, we are mainly interested
      in lossy-to-lossless coding schemes for stereo images allowing progressive
      reconstruction. The most commonly used approaches for stereo compression are
      based on disparity compensation techniques. The basic principle involved in this
      technique first consists of estimating the disparity map. Then, one image is
      considered as a reference and the other is predicted in order to generate a
      residual image. In this paper, we propose a novel approach, based on vector
      lifting schemes (VLS), which offers the advantage of generating two compact
      multiresolution representations of the left and the right views. We present two
      versions of this new scheme. A theoretical analysis of the performance of the
      considered VLS is also conducted. Experimental results indicate a significant
      improvement using the proposed structures compared with conventional methods.

PMID- 19586822
TI  - Content based image retrieval using unclean positive examples.
AB  - Conventional content-based image retrieval (CBIR) schemes employing relevance
      feedback may suffer from some problems in the practical applications. First, most
      ordinary users would like to complete their search in a single interaction
      especially on the web. Second, it is time consuming and difficult to label a lot
      of negative examples with sufficient variety. Third, ordinary users may introduce
      some noisy examples into the query. This correspondence explores solutions to a
      new issue that image retrieval using unclean positive examples. In the proposed
      scheme, multiple feature distances are combined to obtain image similarity using
      classification technology. To handle the noisy positive examples, a new two-step
      strategy is proposed by incorporating the methods of data cleaning and noise
      tolerant classifier. The extensive experiments carried out on two different real
      image collections validate the effectiveness of the proposed scheme.

PMID- 19586823
TI  - A theory of phase singularities for image representation and its applications to
      object tracking and image matching.
AB  - This paper studies phase singularities (PSs) for image representation. We show
      that PSs calculated with Laguerre-Gauss filters contain important information and
      provide a useful tool for image analysis. PSs are invariant to image translation
      and rotation. We introduce several invariant features to characterize the core
      structures around PSs and analyze the stability of PSs to noise addition and
      scale change. We also study the characteristics of PSs in a scale space, which
      lead to a method to select key scales along phase singularity curves. We
      demonstrate two applications of PSs: object tracking and image matching. In
      object tracking, we use the iterative closest point algorithm to determine the
      correspondences of PSs between two adjacent frames. The use of PSs allows us to
      precisely determine the motions of tracked objects. In image matching, we combine
      PSs and scale-invariant feature transform (SIFT) descriptor to deal with the
      variations between two images and examine the proposed method on a benchmark
      database. The results indicate that our method can find more correct matching
      pairs with higher repeatability rates than some well-known methods.

PMID- 19586824
TI  - The new influenza A (H1N1) pandemic.

PMID- 19586825
TI  - Novel swine-origin influenza virus A (H1N1): the first pandemic of the 21st
      century.
AB  - An influenza epidemic was detected in April 2009 at the border between the United
      States and Mexico. The virus was identified soon after to be a swine-origin
      influenza virus A (S-OIV A) (H1N1). This virus has an HA gene that is derived
      from the 1918 swine influenza virus and other genes from human, avian, and
      Eurasian swine influenza viruses. Clinically, it behaves similarly to seasonal
      influenza. The only differentiating characteristics are vomiting and diarrhea in
      a quarter of infected patients, which are rare in seasonal influenza. On June 11,
      2009, the World Health Organization declared the first pandemic of the 21st
      century, caused by S-OIV A (H1N1). Vaccination is the only way to dampen this
      pandemic. Many questions await answers, including the clinical impact of the
      pandemic, optimal doses of vaccine, and the future destiny of the virus. A
      breakthrough in vaccinology against influenza is needed to address the recurring
      influenza pandemic.

PMID- 19586826
TI  - Proposed scoring system to determine small bowel mass lesions using capsule
      endoscopy.
AB  - BACKGROUND/PURPOSE: Capsule endoscopy is a highly sensitive method for the
      detection of small bowel lesions. False-positive findings are important
      confounding factors. This study reports on a scoring system for evaluating the
      role of capsule endoscopy in small bowel tumors. METHODS: Ten men and two women
      (age, 23-79 years) with suspected small bowel tumors were included from 120
      patients referred for capsule endoscopy between March 2004 and March 2008. The
      indications were gastrointestinal bleeding (n = 9), melanoma workup (n = 1),
      physical checkup (n = 1), and iron deficiency anemia (n = 1). The proposed tumor
      score was composed of five components: bleeding, mucosal disruption, an irregular
      surface, color, and white villi. These can be scored for probability of mass
      lesions seen at capsule endoscopy. Small bowel mass lesions were probably present
      in those with a score of >or= 4, and a score of <or= 2 indicated a low
      probability of a small bowel mass lesion. RESULTS: Capsule endoscopy showed
      probable small bowel mass lesions in six patients, and a low lesion probability
      in the other six. Capsule endoscopy showed that new lesions were not detected by
      esophagogastroduodenoscopy or colonoscopy. All six patients with probable small
      bowel tumors were found to have pathological findings upon capsule endoscopy: two
      with lymphangioma, and one each with ileal ectopic pancreas, with melanoma
      metastasis, gastrointestinal lymphoma, and gastrointestinal stromal tumor.
      CONCLUSION: Capsule endoscopy may detect small bowel tumors more reliably by
      using the scoring system outlined. It should be considered in suspected cases of
      small bowel tumor.

PMID- 19586827
TI  - Safety and immunogenicity of a tetravalent polysaccharide vaccine against
      meningococcal disease.
AB  - BACKGROUND/PURPOSE: Meningococcal disease, including meningitis and sepsis,
      usually follows an invasive infection by Neisseria meningitidis, and is a major
      cause of death and morbidity worldwide. Currently available meningococcal
      vaccines that consist of pure capsular polysaccharides (serogroups A, C, W-135
      and Y) are generally safe and efficacious in adults and children aged > 2 years.
      The purpose of this study was to evaluate the immunogenicity, safety and
      reactogenicity of a single dose of GlaxoSmithKline Biologicals' Mencevax ACWY
      vaccine in healthy Taiwanese subjects aged 2-30 years. METHODS: This open, single
      center, Phase III study was conducted in Taiwan. A single dose of the Mencevax
      ACWY vaccine was administered to subjects aged 2-30 years. Immunogenicity and
      safety of the vaccine were evaluated after vaccination. RESULTS: The
      immunogenicity results obtained 1 month after vaccination with Mencevax ACWY
      vaccine indicated that the vaccine elicited a good immune response in vaccinees
      aged 2-30 years. This was both in terms of functional activity directed against
      meningococcal polysaccharide (A, C, W-135 and Y) as measured by serum
      bactericidal assay (> 93% activity against all serogroups), and specific IgG
      concentrations measured by ELISA (> 96% seropositivity to all serogroups).
      CONCLUSION: The tetravalent polysaccharide Mencevax ACWY meningococcal vaccine
      was well tolerated and immunogenic in subjects aged 2-30 years in Taiwan.

PMID- 19586829
TI  - Cadmium concentration and metallothionein expression in prostate cancer and
      benign prostatic hyperplasia of humans.
AB  - BACKGROUND/PURPOSE: Cadmium (Cd) causes various genitourinary disorders and is a
      carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies
      heavy metals. We evaluated changes in Cd concentration and MT expression in human
      prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to
      clarify the relationship between Cd concentration and MT expression in prostatic
      diseases. METHODS: The experimental group consisted of 18 patients who underwent
      radical prostatectomy for CaP. The control group consisted of 35 patients who
      underwent transurethral resection of the prostate for BPH. Tissue samples were
      acquired from the gross tumor site and from resected chips. We determined Cd
      concentration by atomic absorption, MT expression by immunoblotting, and
      immunohistochemical staining. The significance of between-group differences for
      these outcomes was analyzed using Student's t tests. RESULTS: There was no
      statistically significant difference in Cd concentration between the CaP and BPH
      groups. Immunoblots from both groups revealed a single band. The relative
      intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in
      the CaP group. MT expression in patients with BPH was 3.4-fold higher than in
      those with CaP. CONCLUSION: MT may bind heavy metals and protect patients from
      CaP. Additional studies are needed to reveal the factors that influence the
      expression of MT in prostate epithelial cells, and to analyze the free and
      compound forms of Cd at the same time.

PMID- 19586828
TI  - Combination of low-dose nalbuphine and morphine in patient-controlled analgesia
      decreases incidence of opioid-related side effects.
AB  - BACKGROUND/PURPOSE: The addition of ultra-low-dose naloxone to patient-controlled
      analgesia (PCA) with morphine reduces opioid-related side effects. Nalbuphine, a
      mixed opioid agonist-antagonist, may be able to attenuate opioid-related side
      effects. The goal of the present study was to investigate the effect of combined
      low-dose nalbuphine and morphine in PCA for postoperative pain control after
      gynecological surgery. METHODS: This randomized, double-blind, controlled study
      enrolled 174 female patients who were undergoing total abdominal hysterectomy,
      myomectomy, or ovarian tumor excision. In the control group, the PCA formula was
      1 mg/mL pure morphine. In the study group, the PCA formula was 1 mg/mL morphine
      and 10 microg/mL nalbuphine (1:100). Numerical rating score, PCA requirement,
      nausea, vomiting, use of antiemetics, pruritus, use of antipruritics, and opioid
      related adverse events were investigated at 1, 2, 4, and 24 hours
      postoperatively. RESULTS: One hundred and sixty-nine patients completed the
      study: 86 in the control group and 83 in the study group. The incidence of nausea
      was lower in the study group (41%) than in the control group (65%). The incidence
      of vomiting, use of antiemetics, pruritus, and use of antipruritics did not
      differ between the two groups. The numerical rating pain score and PCA
      requirements were not significantly different between the two groups. CONCLUSION:
      Combination of low-dose nalbuphine and morphine in PCA decreases the incidence of
      opioid-related nausea, without affecting the analgesia and PCA requirement. This
      novel combination can improve the quality of PCA used for postoperative pain
      control after gynecological surgery.

PMID- 19586830
TI  - Alterations in oxidative stress status during early alcohol withdrawal in
      alcoholic patients.
AB  - BACKGROUND/PURPOSE: Alcohol-induced oxidative stress is the result of the
      combined production of reactive oxygen species [ROS; e.g. malondialdehyde (MDA),
      an index of lipid peroxidation] and impairment of antioxidant defenses [e.g.
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX),
      which are involved in the elimination of ROS]. Little is known about the
      oxidative stress markers among patients with alcohol dependence in Taiwan. This
      study aimed to investigate serial alterations of various oxidative stress markers
      during early detoxification in alcoholic patients. METHODS: We enrolled 121
      inpatients who fulfilled the DSM-IV-TR criteria for alcohol dependence, and 19
      healthy controls. Fasting serum MDA level and antioxidant activity, including
      SOD, CAT and GPX, were measured at baseline in both groups, and after 1 and 2
      weeks of detoxification in alcoholic patients. RESULTS: MDA level in alcoholics
      was higher at baseline than in healthy controls. It decreased after 1 week of
      detoxification, and normalized at week 2. SOD and GPX activities remained
      significantly lower throughout the 2-week period. CAT activity in alcoholics was
      comparable to that in the controls at baseline, but decreased at week 1 of
      detoxification, and was significantly lower than that in the controls after 2
      weeks. Moreover, baseline MDA level was correlated with baseline CAT activity in
      alcoholics; the magnitude of the decrease in MDA level was correlated with the
      decrease in CAT activity following the 1-week detoxification. CONCLUSION: The
      findings suggest severe oxidative stress and weakened antioxidant activity in
      alcoholic patients, and limited changes in oxidative stress in the early stages
      of alcohol withdrawal.

PMID- 19586831
TI  - Clinical features of osteogenesis imperfecta in Taiwan.
AB  - BACKGROUND/PURPOSE: Osteogenesis imperfecta (OI) (MIM 166200, 166210, 259420 and
      166220) is a congenital disorder characterized by increased bone fragility and
      low bone mass. Information regarding the clinical features of this genetic
      disorder is lacking in Taiwan. This study aimed to characterize the clinical
      features of OI patients in Taiwan to establish a practical correlation for
      distinguishing different clinical subtypes of the disorder. METHODS: A review of
      medical records identified 48 patients with OI (33 female and 15 male; age range,
      2 months to 53 years) from January 1996 to June 2008. Diagnosis and
      classification, using the classification system outlined by Sillence et al, were
      based on clinical and radiological characteristics. We also analyzed the clinical
      presentation, physical examination and bone mineral density (BMD) among the
      different subtypes of OI. RESULTS: Retrospective analysis of the medical records
      revealed that 48 OI patients could be classified into types I (n = 19), III (n =
      10), and IV (n = 19). There were statistically significant differences between
      these three types in terms of height, weight, BMD, dentinogenesis imperfecta,
      bone deformity, scoliosis, walking ability, annual fracture rate, and family
      history. However, no significant differences were noted for blue sclera (p =
      0.075) and hearing loss (p = 0.832). CONCLUSION: Nine of the 11 clinical features
      examined---height, weight, BMD, dentinogenesis imperfecta, bone deformity,
      scoliosis, walking ability, fracture rate, and family history---were
      significantly different among the three types of OI patients. This finding may be
      of help in evaluating patients and establishing their prognosis.

PMID- 19586832
TI  - Relationship between chest wall motion and diaphragmatic excursion in healthy
      adults in supine position.
AB  - BACKGROUND/PURPOSE: There has been a lack of studies that have used both three
      dimensional analysis and imaging tools concurrently to describe lung volume
      changes and breathing pattern in subjects in the supine position. The purpose of
      this study was to investigate the correlation between volume changes estimated by
      optoelectronic plethysmography (OEP) and diaphragmatic excursion (DE) measured by
      ultrasonography of healthy adults in the supine position. METHODS: Twelve healthy
      male subjects (age, 25.08 +/- 6.35 years) were recruited and asked to perform
      tidal and deep breathing in the supine position. The volume changes during chest
      wall motion were quantified from OEP analysis---this was done for the upper
      thorax (UT), lower thorax (LT), and abdominal (AB) compartment. Lung volume was
      measured synchronously via the mouth piece of an electrospirometer. The right
      diaphragmatic movement was measured by ultrasonography. RESULTS: Linear
      regression showed that all three compartments (V UT, V LT and V AB) in the
      inspiratory phase were correlated highly with DE during tidal and deep breathing.
      However, multiple linear regression analysis showed that the VAB contributed 94
      95% of the variance when performing either tidal or deep breathing. A predicted
      equation for diaphragmatic movement during deep breathing was DE = 0.052 + 0.294
      V AB. CONCLUSION: The movement of V AB can be used as an index of DE among the
      normal population in the supine position. Its application in patients requires
      further study.

PMID- 19586833
TI  - Construction of balanced translocation t(1;11)(q42.1;q14.3) probe and screening
      application in genomic samples in Taiwan.
AB  - The disrupted-in-schizophrenia 1 (DISC1) gene is a candidate gene in
      schizophrenia. The balanced t(1;11)(q42.1;q14.3) translocation with a breakpoint
      between exons 8 and 9 of DISC1 has been found to be co-segregated with psychosis
      in a Scottish family. To examine whether the t(1;11)(q42.1;q14.3) translocation
      exists in Taiwanese samples, we constructed a plasmid probe that carried the two
      DNA fragments of chromosome 1 (738 bp) and chromosome 11 (719 bp) that covered
      the breakpoint. This probe was validated using a derived DNA gift from the
      translocation carrier of the Scottish family. We screened genomic DNA samples
      from 619 subjects (507 cases and 112 controls). None of the subjects showed the
      designed polymerase chain reaction (PCR) product detected by the probe. We
      concluded that the significant association between schizophrenia and the DISC1
      gene in the Taiwanese sample was not caused by balance translocation, but rather
      by polymorphic variations of the gene to be detected.

PMID- 19586834
TI  - Early-onset stroke in a patient with nasopharyngeal cancer associated with
      protein C deficiency.
AB  - We report a 47-year-old male stroke patient with nasopharyngeal cancer (NPC) and
      protein C deficiency. The patient was diagnosed with NPC and received a complete
      course of radiotherapy. Infarction stroke occurred 28 months after radiotherapy
      and magnetic resonance imaging of the brain confirmed the diagnosis. Carotid
      duplex sonography showed 50-79% stenosis in his left internal carotid artery.
      Coagulation profiles indicated protein C deficiency. After medical treatment and
      rehabilitation, the patient regained the ability to walk and he could perform
      most of his daily activities. Radiotherapy-induced carotid stenosis is an
      exacerbating feature of stroke in patients with protein C deficiency. We suggest
      early carotid duplex sonography and survey of the coagulation profile to prevent
      a stroke in patients with NPC.

PMID- 19586835
TI  - Attention deficit hyperactivity disorder and increased risk of injury.
AB  - PURPOSE: This study describes the influence of attention deficit hyperactivity
      disorder (ADHD) on the incidence rates of selected injuries. METHODS: A
      retrospective cohort study design was employed using medical claims data from the
      Deseret Mutual Benefit Administrators (DMBA), a health insurance company for
      employees of the Church of Jesus Christ of Latter-day Saints (LDS) and their
      spouses and dependent children. ADHD diagnosis, injury, medication, and
      demographic data were extracted from claims files during 1998-2005 for all
      enrollees aged 0-64 years. RESULTS: Incidence rates of ADHD were 1.83 (95% CI
      1.68-2.00) times greater in males than females and highest in the age group 5-9
      years and income group $80,000 or greater. ADHD increased the risk of selected
      injuries. The most common injuries involved sprains and strains of joints, then
      open wounds of the head, neck and trunk, and upper/lower limb, and then fractures
      of the upper/lower limb. Medication did not significantly protect against injury
      in ADHD patients. The rate of severe injury (i.e., fracture of skull, neck and
      trunk; intracranial injury excluding those with skull fracture; and injuries to
      nerves and spinal cord) was 3.07 (95% CI 2.37-3.98) times more common in ADHD
      enrollees compared with non-ADHD enrollees. Those with 1, 2, 3, or 4 or more
      injuries were 1.67 (1.50-1.86), 2.11 (1.75-2.56), 2.63 (1.80-3.84), and 2.94
      (1.47-5.87) times more likely to have ADHD, respectively. CONCLUSIONS: ADHD is
      positively associated with injuries. More severe injuries have a significantly
      stronger associated with ADHD than less severe injuries.

PMID- 19586836
TI  - [Harold Eliot Varmus].

PMID- 19586838
TI  - [Reviews in comparative genomic research based on orthologs].
AB  - The orthologs have similar or even identical functions in different species,
      share the anological regulatory pathways, and play the close or even same role
      among species. Furthermore, the vast majority of the biological core functions
      were assumed to a considerable number of orthologous genes in organisms.
      Orthologs was the most reliable choices for functional annotation and analysis of
      genomic sequences, whose unique biological characteristics demonstrated that
      comparative genomics research based on orthologs will certainly provide clues for
      detecting the origin, expression, and loss of important functional genes during
      the biological evolution in different organisms. In this review, the fundamental
      characteristics of orthologous genes and the relationship between the orthologs
      and comparison genomics were recounted. The corresponding approaches and the
      current status in comparative genomic research based on the orthologs were
      summarized.

PMID- 19586837
TI  - [Aging or tumor: the crosstalk between telomerase and p53].
AB  - Telomerase and p53 play critical roles in tumorigenesis and senescence. The
      mutation of p53 gene and the reactivation of telomerase have been found in most
      of the human tumors. Aiming telomerase and p53 genes have become important
      strategies in tumor therapy. We reviewed the aging and tumor phenotype in
      different status of telomerase and p53 (mTR/p53+/+; mTR/P53/), which indicated
      that telomere dysfunction could initiate or suppress the tumorigenesis depending
      on the status of p53. This helps further understanding of the crosstalk between
      p53 and telomerase in aging and tumorigenesis, and provides a new idea for
      treating tumor.

PMID- 19586839
TI  - [Recent progress in plant genome size evolution].
AB  - It has been known that eukaryotic genomes span a wide range of sizes regardless
      of organism complexity. The observed differences in genome size are primarily due
      to polyploidy level and abundance of non-coding DNA, especially the contribution
      of transposable elements (TEs). Here we reviewed the current progress in genome
      size variation of plant species and the underlying evolutionary forces that
      contribute to genome expansion or contraction. Polyploidization and the
      accumulation of transposable element are the primary contributors to genome
      expansion. As to the mechanisms of DNA loss, unequal homologous recombination and
      illegitimate recombination are thought to be the counterbalances to the unlimited
      expansion of a genome. The evolutionary direction of plant genome size is also
      discussed, which tends to favor larger genomes with deletion mechanisms acting to
      only attenuate genome expansion but not reverse.

PMID- 19586840
TI  - [Plant SNAREs and their biological functions].
AB  - The signal communication between various organelles is essential for cells of
      eukaryotic organisms. Vesicle trafficking is an important pathway for this kind
      of communication. Most of the membrane fusion is mediated by SNAREs (Soluble N
      ethyl-maleimide-sensitive fusion protein attachment protein receptors), which are
      highly conserved from various species. Compared with genomes of other eukaryotes,
      plant genome encodes an even higher number of SNAREs. Accumulating evidences
      support that plant SNAREs is a multifunctional protein family, which is involved
      in variety of biological processes. We review the recent advances on molecular
      mechanism and biological functions of plant SNAREs.

PMID- 19586841
TI  - [Relationship between IL-10 promoter gene polymorphisms and the susceptibility to
      endometriosis].
AB  - The purpose of this study was to investigate the relationship between IL-10
      promoter gene polymorphism and the susceptibility to endometriosis (EMs) in
      Chinese population. Amplification refractory mutation system polymerase chain
      reactions (ARMS-PCR) and DNA sequencing were performed to detect polymorphism of 
      1082G/A site and PCR-RFLP was used to determine the genotypes in -819T/C and 
      592A/C sites. One hundred and nineteen Chinese women with different stage EMs and
      120 controls were employed in this study. Although there were no significant
      differences in the polymorphism of -1082 site between two groups (P>0.05), the
      frequencies of -819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were
      significantly increased in EMs patients compared with the controls (P<0.05). The
      frequencies of -819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were
      significantly increased in III-IV EMs patients compared with I-IIMs or controls
      (P<0.01). This suggests that polymorphisms of IL-10-819 (T/C) and -592 (A/C) may
      be associated with the susceptibility to EMs in Chinese population.

PMID- 19586843
TI  - [Cloning and expression analysis of porcine ACTA2 gene and its association with
      production traits].
AB  - To identify new DNA markers which have significant impact on pig production
      traits, the full coding sequence and partial genomic sequence of porcine
      ACTA2(Actin alpha 2)gene were isolated using in silico cloning and PCR. PCR-Hinf
      RFLP was developed to detect C1554T substitution in intron 2. The frequency of
      allele C is higher than that of allele T in all the seven detected pig
      populations except for Large White and MeishanxLarge White. Association analysis
      of markers and production traits showed that the relation between ACTA2 gene and
      shoulder fat thickness, buttock fat thickness, fat meat percentage, lean meat
      percentage, meat pH (m.Biceps Femoris, BF), and intramuscular fat were
      significant or highly significant. Compared with CC genotype, TT had a higher
      lean meat percentage, a lower fat meat percentage and backfat thickness. Real
      time RT-PCR analysis showed that the expression level of ACTA2 gene in the
      skeletal muscle of Large White and Meishan pigs decreased with the increasing of
      days. And during each period, the expression level was higher in Meishan pigs
      than in Large White pigs.

PMID- 19586842
TI  - [The genotype-phenotype correlation of the MYH7 gene c.1273G > a mutation in
      familial hypertrophic cardiomyopathy].
AB  - To investigate the genotype-phenotype correlation in Chinese familial
      hypertrophic cardiomyopathy (HCM), peripheral blood samples were collected from 7
      members of a Chinese HCM family, and 120 normal subjects were recruited as
      control. The full encoding exons and flanking sequences of the cardiac troponin T
      (TNNT2) gene, beta-myosin heavy chain (MYH7) gene and myosin binding protein C
      (MYBPC3) gene were amplified and the products were sequenced directly to detect
      the mutations. A missense mutation, c.1273G>A, was identified in exon 14 of the
      MYH7 gene in 4 members of the Chinese HCM family, which resulted a glycine (Gly)
      to arginine (Arg) exchange at amino acid residue 425. The 425th glycine amino
      acid residue is highly conservative across the different species. The clinical
      phenotypes among the family members who carried this mutation presented
      significant individual differences. The c.1273G>A mutation of the MYH7 gene might
      be the causal mutation of the familial HCM. The heterogeneity of phenotypes
      suggested that multiple factors may be involved in the pathogenesis of HCM.

PMID- 19586844
TI  - [Expression levels of Cdc2 and Cdc25A mRNA in cattle, yak, and cattle-yak
      testis].
AB  - The infertility of cattle-yak, which is the hybrid offspring of cattle and yak,
      is a difficult problem in crossbreeding and improvement of yak. Cdc2 and Cdc25A
      are the key genes of meiosis. The decline of their expression levels will cause
      the spermatogenesis failure and lead to infertility. Therefore, this study was
      conducted to study the relationship between the infertility of cattle-yak and the
      expression levels of Cdc2/Cdc25A genes. The expression profiles were obtained by
      RT-PCR. Cdc2 and Cdc25A genes were widely expressed in many tissues, which
      confirmed their important role in cell division and the progression of cell
      cycle. Real-time quantitative PCR analysis indicated that the expression levels
      of Cdc2 and Cdc25A in cattle and yak testis were higher than those in cattle-yak
      (P<0.05). Therefore, low expression levels of Cdc2 and Cdc25A genes may have a
      relationship with the infertility of cattle-yak.

PMID- 19586845
TI  - [Polymorphic and linkage analysis of microsatellite BMS2508 and FecB gene in
      sheep].
AB  - Genetic polymorphisms of microsatellite locus BMS2508, which was closely linked
      to the ovine fecundity gene FecB, were detected in prolific (Small Tail Han
      sheep) and non-prolific breeds of sheep (Texel, Dorset and Chinese Merino). The
      linkage disequilibrium between microsatellite locus BMS2508 and FecB gene of
      Small Tail Han sheep was also analyzed. There was the same mutation (A746G) of
      BMPR-IB gene in Small Tail Han sheep as that of FecB in Booroola Merino ewes, but
      the FecB mutation was absent in Texel, Dorset and Chinese Merino sheep. The
      genotype frequencies of BB, B+ and ++ were 0.485, 0.398 and 0.117 in Small Tail
      Han sheep, respectively. There were eight alleles varied from 94 bp to 116 bp and
      15 genotypes detected at BMS2508 locus in four sheep breeds totally 438
      individual. The preponderant allele was 100 bp, 94 bp, 94 bp, 112 bp, 100 bp, 100
      bp, 112 bp, and the frequency was 0.453, 0.544, 0.802, 0.475, 0.483, 0.439, 0.389
      in Small Tail Han (n=307), Texel (n=45), Dorset (n=46), Chinese Merino (n=40),
      and BB group (n=149), B+ group (n=122), ++ group (n=36) from Small Tail Han,
      respectively. In Small Tail Han sheep, linkage analysis indicated that there was
      certain linkage disequilibrium between 100 bp allele of microsatellite BMS2508
      and B allele of FecB gene (D' =0.408), and certain linkage disequilibrium between
      110 bp and 114 bp alleles of microsatellite BMS2508 and + allele of FecB gene
      (D'=0.513).

PMID- 19586846
TI  - [Mapping QTLs related to head length, eye diameter and eye cross of common carp
      (Cyprinus carpio L.)].
AB  - A common carp gynogenetic line including 44 individuals derived from the cross
      Barbless carp x Hebao-cold tolerance red carp was used to construct a linkage map
      using 445 markers (265 AFLP markers, 127 SSR markers, 37 EST-SSR markers and 16
      RAPD markers). Quantitative traits loci (QTLs) associated with head length, eye
      diameter, and eye cross were identified by composite interval mapping of the
      software WinQTLCart2.5. Five QTLs were identified for head length on the linkage
      group of LG2, LG3, LG40, and LG4, which explained 12.39% to 34.29% of the total
      variation of the head length. All of their additive effects were negative. Two
      QTLs were associated with eye diameter on the linkage groups of LG39 (qED-39-1)
      and LG40 (qED-40-1), which explained 9.77% and 5.62% of the total variation of
      the eye diameter, respectively. The additive effect of qED-39-1 was positive and
      that of qED-40-1 was negative. Two QTLs were responsible for eye cross on the
      linkage group of LG28 and LG20, explaining 8.88% and 8.29% of the total variation
      of the eye cross, respectively. The additive effect of qEC-28-1 was negative and
      that of qEC-20-1 was positive.

PMID- 19586847
TI  - [Identification of microsatellite markers associated with growth traits in
      largemouth bass (Micropterus salmoides L.)].
AB  - Forty microsatellite loci were selected to amplify the genomic DNA of cultured
      stock of largemouth bass (Micropterus salmoides L.) in China. Genotypic
      differences of these microsatellites loci were analyzed using 2-test between the
      maximal weight group and minimal weight group. Sixteen microsatellites showing
      significantly difference (P<0.1) were used in genotyping 121 individuals, and the
      associations between their genotypes and growth traits were examined.
      Microsatellite loci of JZL60, JZL67, JZL72, JZL124, MiSaTPW76, MiSaTPW117 and
      MiSaTPW173 were significantly associated with body weight, body length, and body
      height (P < 0.05 or P < 0.01). The most favorable genotypes for growth traits
      were AA at JZL60, BB at JZL67, AC at JZL72, BB at MiSaTPW76 and BC at MiSaTPW117.
      In addition, a total of 47 alleles for the 16 loci were detected (2 approximately
      5 alleles for each locus). The average effective number of alleles (Ae), observed
      heterozygosity (Ho), expected heterozygosity (He) and mean polymorphic
      information content (PIC) was 2.938, 0.515, 0.500 and 0.445, respectively, both
      of which indicated that the population genetic diversity was medium.

PMID- 19586849
TI  - [Genetic analysis and mapping of high-tillering and dwarf mutant htd1-2 in rice].
AB  - Tillering is one of the most important agronomic traits of rice. In order to
      explore the molecular mechanism of rice tillering, a high-tillering dwarf 1-2
      (htd1-2) mutant was isolated from the offspring of the indica rice (Oryza sativa
      L. ssp. indica) variety 9311 treated with 350Gy 60Co gamma-radiation. Genetic
      analysis showed that both high tillering and dwarf phenotypes of htd1-2 were
      controlled by a single recessive nuclear gene. By means of molecular marker
      technique, the HIGH-TILLERING DWARF1-2(HTD1-2) gene was mapped between two CAPS
      markers A6 and E2 on chromosome 4 within 116 kilobases. Within this region, there
      is a cloned gene HIGH-TILLERING DWARF1(HTD1), which controls rice tillering. By
      comparing sequences of HTD1 between htd1-2 and 9311, in combination with the
      results from dCAPS analysis, we believed that HTD1 is an orthologue of the gene
      HTD1-2. Because of different genetic backgrounds, htd1 and htd1-2 have different
      phenotypes although they are the allelic mutants. Furthermore, removal of
      axillary buds proved that dwarfism of htd1-2 mutant is partly attributed to its
      excessive tillers.

PMID- 19586848
TI  - [Molecular phylogenetic relationships among species in the genus Sorghum based on
      partial Adh1 gene].
AB  - The genus Sorghum contains some important grain crops and economically important
      forage grasses as well as agricultural weeds. The goals of this study were to
      elucidate the phylogenetic relationships between Sorghum species and ascertain
      the taxonomy status of the quarantine weeds which provide bases for effective
      utilization of its germ resources on molecular breeding and improvement of crop
      qualities and thus provide important guidance for port detection. In the present
      study, total DNA from the seeds of 8 Sorghum species (four S. almum, two S.
      halepense, one S. silk and one S. sudanense)were extracted, and the partial Adh1
      gene of about 2,000 bp in length were amplified by PCR using specific primers
      designed from conserved regions of Adh1 gene reported in the GenBank (AF050456)
      and sequenced. Based on these sequences and other 24 Adh1 sequences registered in
      the GenBank, the phylogenetic trees constructed by multiple methods (MP, ML, and
      NJ) with the corresponding Adh1 sequence of Cleistachne sorghoides as the
      outgroup shared almost the same topology. The results showed that: (1) there were
      obviously three lineages for the genus Sorghum. One included two subgenera
      Chaetosorghum and Heterosorghum, and another included subgenus Eusorghum, both of
      which consisted of 2n=20 and 2n=40 species with small chromosomes. Still another
      lineage contained the two subgenera Parasorghum and Stiposorghum with 2n=10
      species and their polyploid relatives with relatively large chromosomes; (2)
      geographical divergence clearly existed in the S. almum; (3) S. purpureosericeum,
      S. versicolor, S. nitidum and S. leiocladum of subgenus Parasorghum clustered
      together, but S. matarankense, S. grande, and S. timorense of the same subgenus
      clustered with the species of subgenus Stiposorghum, showing closer relationship
      with subgenus Stiposorghum; (4) S. macrospermum was more closely related to S.
      laxiflorum than the other species of the genus Sorghum.

PMID- 19586850
TI  - [Differentially expressed genes during Larix somatic embryomaturation and the
      expression profile of partial genes].
AB  - To study the molecular mechanism of Larix somatic embryogenesis, a differentially
      expressed cDNA library of Larix somatic embryo in the period of maturation was
      constructed using suppression subtractive hybridization (SSH). The cDNA from the
      cultures at the stage of somatic embryo maturation of embryogenic cell line Y35
      of L. leptolepis xL. principis-rupprechtii was used as the tester and the cDNA
      from its subcultured callus was used as the driver. Eight hundreds randomly
      selected positive clones were sequenced, and 468 UniGenes were obtained finally.
      According to their function, these ESTs were classified into 19 categories and
      were involved in many biological process related to plant growth and development
      such as metabolism, transcription, signal transduction, transport facilitation,
      cell growth and division, cell structure, cell fate, protein synthesis or
      degradation, defense etc. Real-time PCR results of several ESTs showed that they
      were all differentially expressed at the different stages during cell line Y35
      somatic embryo maturation.

PMID- 19586852
TI  - [Development, optimization and application of the expression analysis platform
      based on multiplex quantitative RT-PCR using fluorescent universal primers].
AB  - A multiplex quantitative RT-PCR technology with a universal fluorescent primer
      was established. This technology employs a chimeric-primer-induced-universal
      primer amplification method that ensures target genes amplified in a constant
      ratio. This technique was cost-effective, moderate-throughput, and reliable in
      quantification of gene expression. It is complementary to cDNA chip, which has
      low quantitative accuracy , and Real-time quantitative PCR with low throughput,
      through improving the entire process of expression profiling analysis. Eleven
      genes within a QTL segment regulating mouse puberty onset on chromosome X were
      investigated to construct and optimize the method. The sensitivity of detection
      (102 copies) was determined, the concentration ratio of universal primer and
      chimeric forward primers (1:1) was optimized, and the accuracy and repeatability
      were validated. The method of Touchdown PCR with addition of universal primers
      significantly improved amplification of genes expressed in low abundance. After
      testing the expression profile of 11 genes in hypothalamus and testis in two
      mouse strains C3H/HeJ and C57BL/6J at the age of 15 d, one gene named PHF6 was
      found differentially expressed for further function analysis.

PMID- 19586851
TI  - [Molecular cloning and expression of alcohol dehydrogenase gene of Phanerochaete
      chrysosporium].
AB  - When Phanerochaete chrysosporium is grown under oxygen-limited condition, ethanol
      is one of the important metabolites. In order to understand the metabolic
      mechanism of P. chrysosporium grown under oxygen-limited condition, a cDNA
      sequence (1 071 bp) designated "PCAdh1" encoding an alcohol dehydrogenase (ADH)
      was cloned from the filamentous white-rot fungus P. chrysosporium. PCAdh1 gene
      encodes a protein of 356 amino acid residues. Although the catalytic domain and
      coenzyme-binding domain were highly conserved, the protein sequence of PCAdh1
      showed a low level of similarity to other known ADH. The recombinant PCAdh1
      protein was expressed in Escherichia coli and its enzyme activity was detected.
      The protein was purified and used to prepare antibody. Semi-quantitative RT-PCR
      and Western blot demonstrated that the expression level of PCAdh1 in P.
      chrysosporium remained stable despite the lowered oxygen content, indicating that
      the gene expression is constitutive. But with the reduction of oxygen content,
      the overall activity of ADH from the crude mycelia proteins was increased during
      the growing periods, implying that the expression of other Adh genes in P.
      chrysosporium is inductive.

PMID- 19586853
TI  - [Mark Steven Ptashne].

PMID- 19586854
TI  - [Current status and strategies for improvement of rice grain chalkiness].
AB  - This paper reviews the current status of correlation between rice chalkiness and
      other rice quality characters, formative mechanism, and classical and molecular
      genetics for rice chalkiness. The formation of rice chalkiness proves to be a
      complicated physiological process and tightly relate to "source-sink" of rice,
      dynamics of grain filing, biosynthesis and accumulation of starch in endosperm.
      Rice chalkiness is a complicated quantitative trait, which is controlled by
      maternal effects, endosperm effects, and cytoplasmic effects. There are some
      stable quantitative trait loci (QTL) for rice chalkiness on many rice
      chromosomes. Of them, three genes controlling rice chalkiness, which have an
      impact on starch synthesis, starch metabolism, and fruit development, have been
      cloned. But the manipulative network and formative mechanisms of rice chalkiness
      remain unclear. At present in breeding practice, decrease of rice chalkiness has
      become one of the main aims in rice quality breeding, especially for indica rice.
      The direction of genetic research and improvement strategy of rice chalkiness in
      future were discussed in this review.

PMID- 19586855
TI  - [Application of atomic force microscopy in chromosome research].
AB  - Atomic force microscopy (AFM) is an effective apparatus for examination of the
      surface structure of specimens with a higher resolution. It can be used for real
      time observation in vacuum, air, and liquid conditions. This review presented the
      basic principle of AFM and its significant advantages in biological sample
      research relative to other types of microscopes and summarized its application in
      chromosome research.

PMID- 19586856
TI  - [Computational biology strategy for identification of complex disease genes].
AB  - For the past two decades, the dominant methods to identify susceptibility genes
      of complex disease were linkage analysis and association study. Linkage analysis
      usually identifies broad intervals, which can encompass dozens to hundreds of
      candidate genes. Transition from quantitative trait loci to gene has been a
      challenge due to the absence of complete functional information for the majority
      of genes in this susceptibility locus and limited knowledge of the link between
      gene function and disease. Recently, computational biology tools that employ
      information extracted from public online databases have been developed. In this
      review, we introduced principles of DGP, GeneSeeker, Prioritizer, PROSPECTR and
      SUSPECTS (P and S), and Endeavor, then used the prediction of susceptibility
      genes for type 2 diabetes mellitus/obesity and osteoporosis as examples to
      elucidate the application of computational biology strategies, and finally
      discuss the limitations and prospects of these methods.

PMID- 19586857
TI  - [Recent advances on sex determining mechanisms of Microtus mandarinus].
AB  - Most mammalian sex determination belongs to male heterogametic type of genetic
      sex determination. Sex determination of most mammals depends on the Y chromosome.
      SRY gene is the testis-determining factor on Y chromosome of most mammals, which
      is thought to be the most important gene in sex determination by far. Recent
      studies on Microtus mandarinus mandarinus demonstrated that the subspecies has Y
      chromosome, but there is no SRY gene on Y chromosome. Sex determination of
      Microtus mandarinus mandarinus is independent of SRY gene. R-spondin1 has also
      been excluded as the sex determination gene of Microtus mandarinus mandarinus.
      This paper reviews recent advances on sex determining mechanisms of Microtus
      mandarinus mandarinus. Possible sex determining mechanisms of Microtus mandarinus
      mandarinus in the absence of SRY gene are also discussed.

PMID- 19586859
TI  - [Prenatal diagnosis of Duchenne and Becker muscular dystrophy by multiplex
      ligation-dependent probe amplification].
AB  - Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked lethal recessive
      disease caused by mutation in the DMD gene. There is no efficient treatment for
      this serious and disabling disease. We established a combination method to detect
      carriers and performed prenatal diagnosis. Using multiplex ligation-dependent
      probe amplification (MLPA) and linkage analysis of short tandem repeats (STR)
      methods, 26 prenatal diagnosis were performed for pregnancies at risk of having a
      DMD/BMD baby through amniocentesis. Seven out of 26 male fetuses were affected
      and the pregnancies were terminated. Four out of 26 female fetuses were found to
      be carriers. MLPA can be the method of choice for initial screening of DMD/BMD
      patients for deletions and duplications mutations. When combined with STR-based
      analysis, it can improve the rate of DMD/BMD prenatal diagnosis.

PMID- 19586858
TI  - [Construction of the oocyte-specific expressing phiC31 integrase vector pZP3-INT
      and its expression in mouse oocytes].
AB  - Streptomyces phage phiC31 integrase is a site-specific recombinase, which can
      catalyze site-specific, unidirectional recombination between the attP site and
      attB site. To explore whether it can be used to mediate the recombination of
      specific gene in oocytes, GV-stage oocytes were collected from 3-week-old Kunming
      White mice by puncturing antral follocles with a sharp needle, and micro-injected
      with oocyte-specific expressing phiC31 integrase vector pZP3-INT and site 
      specific recombination detection vector pBCPB+. phiC31 integrase mRNA were
      detected by RT-PCR and the recombination of pBCPB+ was evaluated by PCR in mouse
      oocytes at 48 h after injection. Both can get corresponding bands. These results
      indicated that the expression of phiC31 integrase can be driven by ZP3 promoter
      efficiently and phiC31 integrase can mediate the site-specific recombination
      between attP site and attB site in mouse GV-stage oocytes. It could be a powerful
      tool for the study of recombination of specific gene in mouse oocytes and would
      provide an alternative way for the mouse oocyte genome manipulation.

PMID- 19586860
TI  - [Gene diagnosis and CAG repeat analysis of spinocerebellar ataxia cases of
      Guangxi region].
AB  - To characterize the distributions and subtypes of the spinocerebellar ataxias
      (SCA) in Guangxi region, the SCAl, SCA2, SCA3/MJD, SCA6, SCA7 and SCA12 (CAG)n
      mutations were analyzed by polymerase chain reaction (PCR) and capillary
      electrophoresis (CE). The SCA3/MJD mutation was detected in a total of 21 SCA
      patients and 19 presymptomatic individuals from 6 SCA families and their CAG
      repeat numbers were 59-70 and 60-73, respectively. No (CAG)n mutations of SCA1,
      SCA2, SCA6, SCA7 and SCA12 were detected. This study showed that SCA in Guangxi
      region is mostly SCA3/MJD subtype and the CAG repeats are smaller than those
      reported in other regions previously.

PMID- 19586861
TI  - [Immunofluorescence patterns of histone H3 lysine 4 dimethylation on X
      chromosomes of different cloned cattle].
AB  - Using immunofluorescence staining, the patterns of histone H3 K4m2 of metaphase X
      chromosomes were measured in cloned cattle derived from FFB and FOV donor cells.
      The results demonstrated that the modification pattern of H3 K4m2 in the ear
      tissue of all clones was largely consistent with that of the donor cell line FFB
      and conventionally produced cattle, but different from that of the donor cell
      line FOV.

PMID- 19586862
TI  - [Association of polymorphism for porcine BF gene with reproductive traits and
      placental efficiency in Large White].
AB  - Taking BF gene as one of the candidate genes influencing on reproductive traits
      in present study, this study used PCR-RFLP analyzised the polymorphism of intron
      1 of BF gene in Large White sows. A single nucleotide polymorphism (SNP) named as
      BF-intron 1-C79T was detected. And the three genotypes of CC, CT, TT got fitted
      Hardy-Weinberg equilibrium with chi2-fitness test. An association analysis was
      tested between the genetic polymorphism at intron 1 and total number born (TNB),
      number born alive (NBA), born weight (BW) and placental efficiency (PE)
      respectively. It showed that, at first parity, the TNB, NBA, BW and PE with CC
      genotype were higher than those with CT genotype but not significant (P>0.05).
      Meanwhile, in multiparous sow population, the TNB, NBA and PE with CC genotype
      were significantly more than those with TT genotype (P<0.05), with increase of
      3.45, 3.92, and 23.80%, respectively. Thus BF-intron 1-C79T is suggested to be a
      potential genetic marker for the breeding on the reproductive traits and
      placental efficiency.

PMID- 19586863
TI  - [Characterization of expression of alpha1-acid glycoprotein gene in Beijing fatty
      chicken (Gallus gallus)].
AB  - The specific expression of alpha1-AGP gene in eight different tissues of Beijing
      fatty chicken was investigated by RT-PCR. The full-length cDNA of alpha1-AGP was
      inserted into pEGFP-C1 multi-cloning sites to construct recombinant eukaryotic
      expression vector pEGFP-alpha1-AGP. The lipofectin method was used to transfect
      the pEGFP-alpha1-AGP into Beijing fatty chicken fibroblast cells. The open
      reading frame of Beijing fatty chicken alpha1-AGP gene was 612 base pairs in
      length, which was expressed higher in liver and lung than in muscle. This gene
      did not express in heart and kidney. The expression efficiency ranged from 31.3%
      to 47.6% in 24, 48, and 72 h after transformation. The green fluorescence mainly
      concentrated in the nucleus. With the increase of the expression of green
      fluorescence, granula was observed in the nucleus. RT-PCR and Western blotting
      analyses showed that pEGFP-alpha1-AGP had been integrated into the genome of
      Beijing chicken fibroblast cell with normal expression level. In optimized
      condition, there was no significant effect (P>0.05) on apoptosis ratio, positive
      cell shape, growth and reduplication state comparing with the control group. This
      research established the foundation for further function research of alpha1-AGP
      gene and application in transgenic animal cloning.

PMID- 19586864
TI  - [The construction of a preliminary genetic linkage map in the Japanese scallop
      Mizuhopecten yessoensis].
AB  - AFLP markers were used to construct the primary linkage map in a family of
      Mizuhopecten yessoensis. A total of 1 855 markers were generated in two parents
      and 52 progenies of the mapping family by using 56 AFLP primer combinations.
      Among the 1 855 markers, 598 were polymorphic and 354 were in agreement with the
      Mendelian segregating ratio of 1:1. Markers segregated according to Mendelian 1:1
      ratio (P>0.05) and 23 distorted markers (0.01<P<0.05) were used in linkage
      analysis. The male map was composed of 178 markers in 22 linkage groups, covering
      a total of 1 263.0 cM with the average interval of 8.1 cM between markers, and
      the observed coverage was 79.4%. The female map was composed of 163 markers in 22
      linkage groups, covering a total of 1 259.5 cM with the average interval of 8.9
      cM between markers, and the observed coverage was 76.8%. AFLP markers showed an
      uneven distribution on the linkage group and there were a lot of markers with a
      distance of 0.

PMID- 19586865
TI  - [Bioinformatics analysis of candidate sequences between two flanking markers
      linked with resistance gene Ht1 to Exserohilum turcicum in maize].
AB  - In order to get Ht1 candidate sequence(s), bioinformatics method was employed to
      analyze sequences between two flanking markers umc22a and umc122a linked with
      Ht1. Sixty-three open reading frame (ORF) sequences were found, fourteen of which
      encoded protein domains. The amino acid sequences encoded by these ORF sequences
      were blasted with the 24 cloned resistance gene amino acid sequences, and a
      phylogenetic tree was constructed. Among the fourteen ORF sequences, gpm565a with
      nucleotide binding site (NBS), containing a lot of random coils, had both high
      identity and close relationship with Xal resistant to bacterial blight, and was
      predicted to be related with Ht1. The remaining thirteen ORF sequences had no
      enough evidence to show any relationships with Ht1 due to lack of conserved
      domains, low identity or distant relationships.

PMID- 19586867
TI  - [Genetic variation and relationship in orchardgrass (Dactylis glomerata L.)
      germplasm detected by SSR markers].
AB  - Genetic variation and relationship of 53 accessions of D. glomerata collected
      from 5 continents were analyzed using simple sequence repeat (SSR) molecular
      markers with 15 SSR primer pairs. The following results were obtained. (1) A
      total of 127 alleles were detected at 15 loci. The number of alleles per locus
      ranged from 5 to 12, with an average of 8.5. The rate of polymorphic sites (P)
      was 95.21%; the polymorphic information content (PIC) ranged from 0.30(A04C24)to
      0.44(A01F24) with an average of 0.36. (2) The genetic similarity (GS) among all
      accessions ranged from 0.43 to 0.94, for all geographical groups GS ranged from
      0.73 to 0.91, and high genetic diversity was observed in Asia (P, 90.55%) and
      Europe (P, 86.61%) groups. These results suggested that there was rich genetic
      diversity among all orchardgrass accessions tested. (3) Based on the cluster and
      principal component analyses, 53 accessions could be divided into five groups
      according to the nearest phylogenetic relationship, and accessions from the same
      continent were classified into the same group associated with their geographical
      distributions.

PMID- 19586866
TI  - [Expressing and functional analysis of GmMYBJ6 from soybean].
AB  - MYB transcription factor is one of the largest families in plants, which plays an
      important role in regulating plant development and physiological metabolism. In
      this study, the expression and function of the new MYB transcription factor gene
      GmMYBJ6 (GenBank No. DQ902863), isolated from soybean (Glycine max L.), were
      characterized. The expression pattern of GmMYBJ6 in different organs was examined
      using Northern blotting analysis. The expression of GmMYBJ6 was detected only in
      the leaves. The transcriptional activation ability of GmMYBJ6 protein was
      confirmed by the yeast assay system and the activity of beta-galactosidase was
      28.48 U/mL. The green fluorescent protein expression vector p163-GFP-GmMYBJ6 was
      constructed and transformed into the epidermal cells of onion via particle
      bombardmental method. The results of instantaneous expression showed that GmMYBJ6
      proteins were localized in cell nucleus. Semi-quantitative RT-PCR analysis
      indicated that GmMYBJ6 improved the expression of certain flavonoid biosynthetic
      genes, such as PAL (Phenylalanine ammonia lyase), C4H (cinnamate-4-hydroxylase),
      4CL (4-coumaroyl-CoA ligase), CHS (Chalcone synthase), CHI (Chalcone isomerase),
      F3H (Flavanone 3-hydroxylase), and FLS (Flavonol synthase), resulting an increase
      of the total flavonoid levels in positive tobacco transformants. Additionally,
      the increasing expression of GmMYBJ6 in soybean cultivar Zhongdou 27, induced by
      UV-B radiation, drought, and high-salt treatment, indicated that GmMYBJ6 was
      associated with response to abiotic stresses.

PMID- 19586868
TI  - [Fruit-specific expression of sweet protein Brazzein in transgenic tomato
      plants].
AB  - The AGPL1 (ADP-glucose pyrophosphorylase large subunit 1) promoter from
      watermelon (Citrullus vulgaris S.) has proved to exhibit fruit-specific
      expression patterns in tomato (Lycopersicon esculentum L.). A plant expression
      vector harboring sweet-taste protein, Brazzein, directed by AGPL1 promoter, was
      constructed and transferred into tomato plants through Agrobacterium-mediated
      transform methods. Histochemical staining assay, PCR screening, Southern blotting
      analysis and RT-PCR analysis showed that Brazzein gene was successfully
      integrated into the genome of transgenic tomato plants with stable expression.
      Sweet-taste fruits were produced under control of fruit-specific AGPL1 promoter,
      whereas other parameters of fruit quality were largely unchanged.

PMID- 19586869
TI  - [Low-background and high-resolution contracted silver-stained method in
      polyacrylamide gels electrophoresis].
AB  - The disadvantage of time-consuming and fussy steps of conventional silver-stained
      method for polyacrylamide gels is evident, and has become the choke point in its
      application. In this paper, a low-background and high-resolution contracted
      silver-stained method for polyacrylamide gels was established. Compared with the
      conventional banding method, this contracted method has fewer steps and needs
      fewer reagents, in particular, lower NaOH concentration. It is rapid and
      economic, especially for mass silver-staining.

PMID- 19586870
TI  - [Martin John Evans].

PMID- 19586871
TI  - [Advances in genetics of restless legs syndrome].
AB  - Recent advances in genetic studies on restless legs syndrome (RLS) have led to a
      series of important discoveries that greatly expand our knowledge on the
      molecular basis of this disease. RLS is a common and complex disease. Several
      genetic epidemiological studies and twin studies have characterized the genetic
      components of RLS and suggest that it is a highly heritable trait with
      heritability estimates of about 50%. The five chromosomal positions (12q13-23,
      14q13-21, 9p24-22, 2q33, and 20p13) have been determined either by model-based
      linkage analysis or by model-free linkage analysis, which have provided the
      linkage maps for positional cloning of the underlying genes or susceptibility
      genes for this disorder. Most recent genome-wide association studies based on
      high-throughput SNP genotyping platforms have also defined three significantly
      associated RLS regions (6p21.2, 2p 14, and 15q23). By integrating with our recent
      genetic studies for this neurological disorder, we reviewed the most important
      findings achieved in genetic studies of RLS.

PMID- 19586872
TI  - [In vivo delivery of siRNA].
AB  - RNA interference (RNAi) is a mechanism of posttranscriptional gene silencing
      mediated by small interfering RNA (siRNA). The ability of synthetic siRNA to
      silence genes in vivo has made it well suited as therapeutic drug, but the
      instability and polarity of siRNA and the complexity of in vivo circumstances
      retarded rapid development of RNAi-based therapies. In this review, a summary of
      the advances on in vivo siRNA delivery is presented and discussed.

PMID- 19586873
TI  - [Combining phylogenetic information: concept, methodology, and challenges].
AB  - The DNA sequences, morphological and other homologous characters can be used to
      infer the origins and histories of biological taxa. Combining all the
      phylogenetic information available can produce more inclusive phylogenies,
      improve our understanding of living organisms, and enable biologists to prompt
      and test hypotheses on a larger scale and with stronger statistical power. In
      this article, the concept of combining phylogenetic information and its
      comparison with traditional analysis were reviewed. The most popular approaches
      of supertree and supermatrix were discussed in detail, and novel ways were
      presented. Although the combining analysis is facing rigid challenges from data
      and foundation, it is currently the only approach for realization of the
      Tree(Net) of Life, and its development will definitely expand our knowledge of
      evolution on the earth and contribute to the progress of evolutionary related
      disciplines.

PMID- 19586874
TI  - [Biosynthesis, catabolism and related signal regulations of plant chlorophyll].
AB  - Plant photosynthesis is determined by chlorophyll (Chl) metabolism, which is an
      important factor of determining crop yield. The genes involved in Chl
      biosynthesis, catabolism, and related signal regulations are numerous, and the
      mutation of any of them may change the pigment level, causing abnormalities in
      leaf color and even inducing individual death. Spontaneous or artificial mutants
      are necessary for functional analysis of Chl related genes. At present, Chl
      mutants are widely used in foundational research and production practice. This
      article reviews the latest research progress in this field.

PMID- 19586875
TI  - [Mutations of Cx26 gene in patients with NSHL and intracellular distribution of
      two mutants].
AB  - To analyze the frequencies and characteristics of Cx26 gene mutations in Chinese
      patients with nonsyndromic hearing loss (NSHL) and investigate the intracellular
      localization of two mutants, 139 unrelated familial cases with non-syndromic
      hearing loss were screened for mutation in Cx26 gene by direct sequencing. Two
      mutants, p.F115C and p.V37I, were structured into pEGFP vectors and transfected
      into Hela cells to detect their expression and fluorescent localization in cells.
      Cx26 variations were detected in 31 patients, with a detection rate of 22.3%. The
      10 variations included 6 types of mutations and 4 types of polymorphisms. A novel
      variation p.F115C was found. The fluorescent localization assay of the two
      mutants p.F115C and p.V37I showed no difference from the wild-type, indicating
      that both mutants did not impair the formation of the gap junctions.

PMID- 19586876
TI  - [Effects of H-FABP gene polymorphisms and nutritional factors on pork quality].
AB  - Pork quality is affected by both genetic and nutritional factors. However, few
      researches focused simultaneously on the effects of these two kinds of factors.
      In order to study the co-effects of these two kinds of factors simultaneously, we
      implemented this experiment, 136 PIC hybrid pigs with about 65 kg body weight
      were randomly divided into 4 groups; each group was fed with a different kind of
      rations. After 35 days of feeding, the pigs were slaughtered at about 95 kg body
      weight and the pork quality was evaluated. Then the polymorphism of H-FABP gene
      was analyzed and an association analysis was conducted. The results are as
      follows: (1) feed ingredient has very significant effect on meat color (MC),
      pH24, intramuscular fat (IMF, %), and intramuscular protein (IMP, %); (2) H-FABP
      gene polymorphism has very significant effect on IMF (%) and IMP (%); (3) the
      interaction between gene and feed ingredient has significant effect on pH and IMF
      (%), and pH and IMF (%) were the highest for AA genotype in group 0 and group 1,
      respectively. These results suggest that both genetic and nutritional factors
      should be concerned in the improvement of pork quality.

PMID- 19586877
TI  - [Effects of rosiglitazone on expression patterns of the genes involved in
      adipogenesis during porcine preadipocytes differentiation].
AB  - To investigate the effects of rosiglitazone on porcine preadipocytes during the
      induced differentiation process, we isolated subcutaneous adipose from two-days
      old piglets using collagenase-digestion method and cultured preadipocyte cells in
      the control and experimental medium, respectively. The control group was under
      the conditions of 10% fetal calf serum in DMEM/F-12 (1:1), insulin (50 nmol/L),
      dexamethasone (100 nmol/L) and 1-methyl-3-isobutylxanthine (0.25 mmol/L), while
      the experimental medium was added with 100 nmol/L rosiglitazone. The expression
      changes of genes associated with adipogenesis between the two different
      conditions were measured by using qRT-PCR. The results revealed that, in the
      experimental group, the expression levels of PPARalpha, PPARgamma, C/EBPalpha,
      FABP4, FASN and GPAT were up-regulated to the maximum at 48 h, 48 h, 48 h, 108 h,
      60 h and 24 h after induction, respectively, and the change folds of these genes
      were 1.7, 48, 3.3, 487.5, 5.8 and 3.6, respectively. While, in the control group,
      the expression levels of these six genes were up-regulated to the maximum at
      different time points (84 h, 96 h, 48 h, 96 h, 36 h and 36 h, respectively) after
      induction, and the change folds of these genes were also different (2.1, 11, 1.6,
      216.5, 3.5 and 2.8, respectively). In addition, a good correlation among the
      expression changes of GPAT and PPARalpha, FASN were all observed at P&0.05 in the
      experimental group and at P&0.01 in control group. These results indicated that
      the expression of PPARgamma, C/EBPalpha, FABP4, FASN and GPAT were strongly up
      regulated, and the expression of PPARalpha was down-regulated under the effects
      of rosiglitazon. These results suggest that rosiglitazone has a promotive effect
      on PPARgamma and C/EBPalpha. Here, we present three tentatively conclusions.
      First, PPARgamma and C/EBPalpha might be the key transcriptional factors for
      preadipocytes differentiation. Second, the phospholipids biosynthesis might
      appear more earlier during the process of adipogenesis. Third, PPARalpha might
      play an important role in the regulation of phospholipids biosynthesis.

PMID- 19586879
TI  - [The expression analysis of Grb10 during mouse embryonic development].
AB  - Grb10 gene expression was analyzed in fetus and four organs during gestation
      process using the real-time RT-PCR and in situ hybridization. The real-time RT
      PCR analysis result showed that the expression of Grb10 in whole embryos is
      throughout E8.5 to E19.5. The Grb10 gene expression level was gradually increased
      from E8.5 to E13.5, and then gradually reduced. The tissues specific expression
      levels were decreased in brain, heart, and lung from E12.5 to E19.5, but a peak
      expression was observed in liver at E18.5. Grb10 gene expression was also
      investigated at E13.5, E15.5, E16.5 and E18.5 sections by using in situ
      hybridization analysis. Strong signals of Grb10 were detected in brain, spine,
      kidney, and muscle tissues. These results suggest that Grb10 may play an
      important role during the development process in mouse.

PMID- 19586878
TI  - [Study on single nucleotide polymorphisms of H-FABP gene in sheep].
AB  - PCR-SSCP and DNA sequencing approaches were applied to assess the single
      nucleotide polymorphisms (SNPs) and analyze the genetic polymorphisms at partial
      exon 2 and intron 2 of H-FABP(Heart fatty acid-binding protein)gene, and five
      sheep populations that comprised of Small-Tailed Han sheep (SH, 48), Ningxia Tan
      sheep (Tan, 121), Tan x SH F1 (23), Poll Dorset (48) and Suffolk (24) sheep were
      screened in this study. The result showed: (1)four SNPs at 981(G/A), 1014(A/C)
      1019(T/C) and 1058 (-/G ) and nine genotypes (AA, BB, CC, AB, AC, BC, AD, CD and
      BD) were detected using primer 2, the AA was the predominant genotype. A chi
      square analysis suggested that the allele frequencies and genotype frequencies of
      H-FABP were in Hardy-Weinberg equilibrium except the Tan and Suffolk populations.
      Statistical analysis revealed a low polymorphism information content (PIC) in the
      Suffolk and Tan x SH F1 populations (PIC amp; 0.25) but an intermediate PIC in
      the remaining three populations (0.25 amp; PIC amp;0.50). It meant that the
      fragment of H-FABP had polymorphisms, which could be used as a candidate gene
      associated gene with phenotypic traits like intramuscular fat content in
      different sheep populations. (2)Three genotypes (HH, Hh and hh) determined by a
      SNP at 2407(T-C) were detected using primer 4. The genotype frequencies were in
      the order of HHHhhh. A chi-square analysis suggested that the allele frequencies
      and genotype frequencies of H-FABP were in Hardy-Weinberg equilibrium in the Tan
      and Poll Dorset populations, and the PIC values were low (PIC amp; 0.25).
      However, there was no polymorphisms in SH, Tan x SH F1 and Suffolk populations.

PMID- 19586880
TI  - [Substitution mapping of QTL for panicle exertion using CSSL in rice (Oryza
      sativa L.)].
AB  - Panicle exertion, the distance between the leaf cushion of flag and the neck
      panicle node, is an important morphological trait, which has significant impact
      on hybrid seed production of rice. In this study, 94 chromosome segment
      substitution lines (CSSL), derived from 9311/Nipponbare with 9311 as the
      recurrent parent, were used to analyze quantitative trait loci (QTL) controlling
      the panicle exertion. The results showed that 17 CSSL contained QTL for the
      panicle exertion. Using substitution mapping, 8 QTLs were mapped on rice
      chromosomes 2, 3, 7, 8, 9, and 11, respectively. The QTL additive effect ranged
      from 0.10 to 3.20, and the additive effects of qPE-9 and qPE-11 were 3.15 and
      2.95, respectively, showing the feature of a major gene. In addition, qPE-2-2,
      qPE-3-1, qPE-3-2, qPE-7, and qPE-8 were mapped in a marker interval less than
      10.0 cM. Mapping of the QTL has laid a foundation for improving the panicle
      exertion with marker-assisted selection and cloning of the QTL in rice.

PMID- 19586881
TI  - [Molecular cloning and protein structure analyses of red/blue light chimeric
      photoreceptor from Allantodia dilatata (Bl.) Ching].
AB  - Phytochrome 3 (PHY3) is a novel chimeric photoreceptor that can respond to both
      red/far red and blue light. Using this photoreceptor, some cryptogams could
      enhance light sensitivity under low light environment. But PHY3 sequence
      information is still extremely limited. In the present study, a full-length PHY3
      genomic sequence was cloned from a fern Allantodia dilatata (Bl.) Ching by
      inverse PCR approaches. Sequence analysis showed that introns were absent in the
      gene. It contained a 4 278 bp open reading frame, encoding a deduced protein of 1
      425 amino acid residues with a theoretical isoelectric point (pI) of 6.29 and a
      calculated molecular mass about 157 kDa. Protein domain search and structure
      analyses indicated that PHY3 originated from the recombination of two different
      photoreceptors. Its N-terminal section consisted of a putative functional
      phytochrome chromophore-binding domain including PAS, GAF, and PHY, whereas the C
      terminal region possessed a nearly complete phototropin motif with two LOV and
      one STKc domains.

PMID- 19586883
TI  - [Exploration and practice of inquiring teaching for the experiments of genetics].
AB  - Aiming for fostering talents with the sense and ability of creation, the current
      wave of experimental teaching reform demands significant improvements in
      genetics. We proposed a train of thoughts about transforming the testing and
      verifying experiments of genetics into inquiring forms with comprehensive or
      designing property, and gave some examples to carry out inquiring teaching for
      the experiments of genetics.

PMID- 19586882
TI  - [cDNA-AFLP analysis on transcripts associated with bolting in Brassica rapa L.
      ssp. pekinensis].
AB  - Premature bolting, caused by low temperature in spring and summer cultivation in
      low land and high land respectively, leads to reduction of the yield and quality
      of the harvested products in Chinese cabbage. Therefore, exploring genes involved
      in vernalization response is important to the improvement of Chinese cabbage
      varieties. Here, one extremely early bolting line (DH-54) and one extremely late
      bolting line (DH-43) were employed, and the cDNA-AFLP approach was used to
      identify key components involved in the low-temperature required vernalization
      response. Of 256 primer recombinations screened, a total of 191 differential
      expressed transcript-derived fragments (TDFs) were identified, and 82 TDFs were
      sequenced. BLAST and alignments showed that 52 candidate TDFs shared high levels
      of similarity with genes of known function, 22 TDFs of unknown function and 8
      novel ESTs. The TDFs of known function were involved in genes encoding enzymes
      working in metabolism, proteins related to stress and defense, signal
      transduction, and transcription regulation, etc.

PMID- 19586884
TI  - [Hsing wen li].

PMID- 19586885
TI  - [Copy-number variation: a new pattern of structural diversity in genome].
AB  - Copy number variation (CNV) is increasingly recognized as a source of inter
      individual differences in genome sequence and has been proposed as a driving
      force for genome evolution and phenotypic variation. Many CNVs resulted in
      different levels of gene expression, which may account for a significant
      proportion of normal phenotypic variation and human diseases. This review
      unveiled the research process and study strategy of CNVs. Subsequently, the
      potential mechanisms of CNV formation and its clinical implications were
      discussed. In addition, the first-generation copy number variation map of the
      human genome was introduced, which demonstrated that DNA copy number variation
      was associated with specific chromosomal rearrangements and genomic disorders.

PMID- 19586886
TI  - [Progresses on immune-related genes and proteins of abalones].
AB  - Abalones, belonging to one of the largest marine gastropod mollusks, are
      economically important seafood in aquaculture worldwide. In recent years,
      bacterial epidemic infection has been reported in China and other countries, and
      mass mortality in abalones causes significant economic losses. Immune-related
      genes and proteins of abalones are seldom reported. However, these functional
      molecules may play a key role in resisting diseases and maintaining healthy
      status and are pivotal for studying immunological mechanisms. Here we summarized
      the advanced research and progresses in abalone immune-related genes and proteins
      with the purpose of facilitating future study of these target molecules involved
      in immunological mechanisms.

PMID- 19586887
TI  - [Principle of diversity arrays technology (DArT) and its applications in genetic
      research of plants].
AB  - Diversity arrays technology (DArT) is a microarray hybridization-based molecular
      marker technique, and a novel method to discover genetic polymorphic markers.
      DArT has recently been applied in genetic research of plants because of its
      characteristics of sequence-independent, high-throughput, fast, low-cost. We
      briefly introduce the principle, characteristics, protocol of DArT and its
      application in genetic research of plants.

PMID- 19586888
TI  - [Advances on bioinformatic research in transcription factor binding sites].
AB  - Transcription regulation is carried out by the interactions between transcription
      factors and their binding sites in DNA. Transcription factor binding sites (TFBS)
      are short, degenerate nucleotide sequences, and usually are 6-20 bp long.
      Accurate prediction of TFBSs is a crucial step towards understanding the
      regulation mechanism of transcription and constructing transcriptional regulatory
      networks. Currently, high-throughput technologies, such as ChIP-chip, are
      producing a large amount of data for TFBS study. TFBS prediction using either
      ChIP-chip data or multiple genome information is becoming a hot topic in
      bioinformatics. In this review, we summarize experimental techniques for locating
      TFBS and databases for TFBS study and further statistical survey models for TFBS
      description and software for TFBS prediction. As a consequence, we believe that
      bioinformatical and experimental studies of TFBS will promote each other in the
      future to understand the nature of transcriptional regulation.

PMID- 19586889
TI  - [The mechanism of TBX5 abnormal expression in simple congenital heart disease].
AB  - To explore the mechanism of TBX5 abnormal expression in simple congenital heart
      disease (CHD), 100 CHD venous blood, 50 CHD heart tissues, and 5 non-CHD heart
      tissues were involved in this study. The mutation and methylation in the 1 200 bp
      region upstream of TBX5 gene were detected by high-performance liquid
      chromatography (DHPLC) and methylation-sensitive restriction endonuclease (MS
      RE), respectively. The binding site of NKX2-5 to Tbx5 predicted by P-MATCH
      software was validated by EMSA (Electrophoretic mobility shift assay). Tbx5 gene
      expression in mouse cardiac muscle cell H9C2(2-1) transfected with NKX2-5
      expression vector was evaluated. No mutation was found in all patients. Both non
      CHD and CHD heart tissues had the same methylation in the two CpG islands.
      Exogenous Nkx2-5 efficiently activated the transcription of the endogenous Tbx5
      gene in H9C2 (2-1) cells. EMSA showed that the special binding band appeared when
      Nkx2-5 existed. These results indicates that the down expression of TBX5 might
      not be caused by mutation and methylation in the 1 200 bp region upstream of
      gene, and might be regulated by abnormal expression of NKX2-5 gene in heart
      muscle of CHD.

PMID- 19586890
TI  - [Polymorphism and forensic applications of miniSTR loci D10S1248, D2S441,
      D1S1677, D9S1122, and D10S1435 in Northwestern Han population].
AB  - To investigate the polymorphism, genetic stability and the value for analysis
      degraded samples of D10S1248/ D2S441/D1S1677/D9S1122/D10S1435 five loci in
      northwestern Han population. The lengths of fragments were analyzed by
      fluorescence PCR and ABI310 Genetic Analyzer. Samples from 154 unrelated
      northwestern Han individuals, 10 genealogies and 10 highly degraded specimens
      were genotyped. Among the 154 unrelated northwestern Han individuals, we
      discovered 8, 7, 7, 6, and 7 alleles in the five miniSTR loci, respectively. The
      frequency distributions in the loci showed no deviations from Hardy-Weinberg
      equilibrium expectations. The H is at 0.662-0.792, PD is at 0.869-0.915, PE is at
      0.382-0.585, and PIC is at 0.650-0.750.The research of genetic stability and the
      value for analysis degraded sample indicated that the five miniSTR loci had high
      genetic stability and could analysis the degraded samples effectively. Therefore,
      these 5 miniSTR loci can be used as genetic markers of Northwestern Han
      populations in forensic practice involving individual identification and
      paternity testing from degraded DNA samples.

PMID- 19586891
TI  - [DNA methylation patterns of mouse tetraploid embryos].
AB  - In the present study, the DNA methylation patterns of in vitro-derived mouse
      tetraploid embryos were investigated by immunofluorescence staining with an
      antibody against 5-methylcytosine (5MeC). Tetraploid embryos could be produced by
      electrofusion at the stage of two-cell embryos, which could develop to
      blastocysts followed by fusion of cytoplasm and nucleus and cleavage in vitro.
      During the fusion of cytoplasm, the DNA methylation levels of the fused embryos
      are as high as these of two-cell diploid embryos in vivo Then the embryos are
      rapidly demethylated when the nucleus begin to fuse, resulting in the lowest DNA
      methylation levels when the nucleus are fused completely. After that, the DNA
      methylation levels of the fused embryos are gradually increased until the morula
      stage. However, whereas an asymmetric distribution of DNA methylation is
      established in vivo-derived blastocysts with a higher methylation level in the
      inner cell mass (ICM) than that in the trophectoderm, we can not detect the
      asymmetric distribution in most in vitro-derived tetraploid blastocysts. So the
      DNA methylation patterns of mouse tetraploid embryos are aberrant, which may lead
      to subsequent developmental failure and embryo death. This is the first report on
      the methylation patterns of in vitro-derived mouse tetraploid embryos.

PMID- 19586892
TI  - [Genetic polymorphism in 5'-flanking region of the lactoferrin gene and its
      associations with mastitis in Chinese Holstein cows].
AB  - Bovine lactoferrin (LF) is a multifunctional glycoprotein found in milk, which
      acts mainly as a defense factor in the mammary gland. Polymorphism has been found
      in the bovine LF gene. However, there is no report on genetic polymorphism of LF
      gene and its associations with mastitis in dairy cattle. In this study, the
      promoter fragment of LF gene containing -926(G/A), -915(T/G), -478(/G), and
      +72(T/C) mutations were genotyped by the PCR-RFLP and CRS-PCR method. Two hundred
      and sixty-eight Chinese Holstein cows were screened. Least square linear model
      (LSM) analysis was applied to evaluate the associations of LF gene with somatic
      cell score (SCS). The results indicated that the SCS was significantly affected
      by -478(/G) and +72(T/C), but not by the other two loci (P >0.05). The SCS of cow
      with genotype AB in +72(T/C) position was significantly lower than that of
      genotype AA (P<0.01) or AB (P<0.05). In position -478(/G), the cow with genotype
      CC showed significantly lower SCS in contrast to cow with genotype CD and DD (P <
      0.01). In conclusion, genotype AB in position +72(T/C) and genotype CC in
      position -478(/G) of LF gene were advantageous genotype, which can be used as
      candidate markers for mastitis resistance selection in dairy cattle.

PMID- 19586893
TI  - [Function of inducible nitric oxide synthase on adaptability to hypoxia in
      Tibetan chicken].
AB  - The inducible nitric-oxide synthase (iNOS) can be induced by hypoxia to produce
      NO, which regulates blood flow and improves oxygen delivery to tissues. In
      present study, SNPs in coding and 5'-flanking regions of iNOS gene were examined
      in Tibetan chicken and lowland chicken using sequence and PCR-RFLP methods, and
      the quantitive express of mRNA of iNOS and the enzyme activity were measured in
      chorioallantoic membrane of chick embryo that was incubated under hypoxic and
      normal conditions. The results showed that a special SNP (-870C-->T)was found in
      5'-flanking region of iNOS gene. Tibetan chicken has higher frequencies in
      mutation allele T than lowland chicken. In hypoxic incubation, the mRNA
      expression of iNOS and enzyme activity were higher in Tibetan chicken than that
      in Dwarf chicken. It was concluded that the mutation of iNOS and hypoxic increase
      of its expression were important base for adaptability to hypoxia in Tibetan
      chicken.

PMID- 19586894
TI  - [Studies on quantitative trait loci related to activity of lactate dehydrogenase
      in common carp (Cyprinus carpio)].
AB  - The reciprocal intergeneric hybrids between common wheat and Roegneria kamoji
      were successfully obtained by means of embryo culture. Morphology, chromosome
      pairing behavior at meiosis, fertility, and resistance to scab of the hybrid F1
      and BC1 were studied. The results showed that the morphology of the reciprocal
      intergeneric hybrids F1 between R. kamoji and T. aestivum cv. Chinese Spring were
      intermediate type between the two parental species. The chromosome configuration
      at metaphase I (MI) of pollen mother cell (PMC) in reciprocal F1 was 40.33I +
      0.78II + 0.03III and 40.40I + 0.79II, respectively. All of the F1 plants showed
      complete male sterility, and the seeds of BC1 were obtained by backcrossing with
      Chinese Spring pollen. The somatic chromosome numbers in BC1 plants of (R. kamoji
      x Chinese Spring) F1 x Chinese Spring ranged from 55 to 63. Many univalents were
      observed at MI of PMC, which resulted in the sterility of BC1 plants. Similarly,
      the chromosome numbers in BC1 plants of (Chinese Spring xR. kamoji) F1 x Chinese
      Spring also ranged from 55 to 63; however, many bivalents at MI of PMC and
      fertile pollen were observed resulting in partial fruitfulness in some BC1 plants
      by self-crossing. A plant (2n=63) with 42 wheat chromosomes and 21 R. kamoji
      chromosomes was obtained from R. kamoji x Chinese Spring cross, which had a
      chromosome configuration at MI of 26.40I + 18.30II. Because many univalents
      existed, this plant showed complete male sterility, and BC1 plants were obtained
      by back-crossing with Chinese Spring as the pollen parent. The chromosome numbers
      of BC1 ranged from 40 to 59, which contained less alien chromosomes. Although the
      morphology of the spike in BC1 plants was similar to that of Chinese Spring,
      these BC1 plants were still sterile. All F1 and most of the BC1 plants showed
      high resistance to Fusarium graminearum, which indicated that the resistance to
      scab from R. kmoji can be transferred into wheat.Microsatellite markers were used
      to make marker regression analysis on activity of lactate dehydrogenase based on
      double pseudo-testcross strategy using Windows Map Manager2.0 software. The
      parents that came from the cross between progenies of Hebao-cold tolerance red
      carp and Barbless carp and F2 progenies were used as segregating populations. For
      maker regression, a total of 12 markers associated with activity of lactate
      dehydrogenase were significant at P<0.05 and HLJE222 was significant at P<0.01.
      The variance explained by these loci, ranged from 4.00% to 10.00%. Locus HLJE222
      was closely linked to the gene related to activity of lactate dehydrogenase of
      common carp. For further identification, EST-SSR markers were used to screen the
      protein and nucleotide database using bioinformatics tools in order to find the
      homologies. High sequence similarities of HLJE222 marker were observed with the
      nucleotide sequence of DAZ associated protein 1mRNA of zebrafish(94%), and
      protein sequence of DAZ associated protein 1(97%). DAZ protein is one of the
      short chain dehydrogenases, which is an important enzyme in the process of
      glucose metabolism in the organisms. This family contains a wide variety of
      dehydrogenases. This indicates that locus HLJE222 was closely linked to the gene
      associated with activity of lactate dehydrogenase of common carp.

PMID- 19586895
TI  - [Comparative assessment of SSR diversity in aromatic rice germplasm].
AB  - The genetic diversity in 370 aromatic rice germplasms introduced from home and
      abroad, was investigated by using a total of 60 SSR markers. 361 alleles were
      detected, with the number of alleles (Na) per loci ranging from 2 to 10. The
      Nei's genetic diversity index (He) among loci varied widely from 0.104 at RM308
      to 0.885 at RM2634 with an average value of 0.663. There was an obvious
      difference in SSR allelic diversity between indica and japonica rice. Indica rice
      showed more variation than japonica rice both for Na and He. Meanwhile, the
      genetic diversity of the landraces was higher than that of the improved
      varieties, and Na of the improved varieties was 86.5% of the landraces. Analysis
      of molecular variance indicated that 43.08% of the variation was from genetic
      differences between subspecies. It was also demonstrated that the genetic
      differentiation among different rice ecological regions ranged from 1.69% to
      14.40%. There was significant differentiation between Southern China and
      Southwestern China, Central China and Southwestern China, respectively. Cluster
      analysis showed that 370 aromatic rice varieties were mainly classified into
      indica and japonica, and aromatic rice varieties from the same areas or the
      neighboring provinces were basically assigned to the same group.

PMID- 19586896
TI  - [Analysis of the chromosomes of S. bicolor x S. propinquum and S. dochna x S.
      propinquum by FISH].
AB  - By means of fluorescence in situ hybridization (FISH), we located and analyzed
      the sites of the 45S rDNA on the F1 hybrids of S. bicolor x S. propinquum and S.
      dochnaxS.propinquum. Two signals of 45S rDNA were mapped on the mitotic metaphase
      chromosomes in the F1 hybrids, respectively, and one signal was present on a
      bivalent during meiotic of synaptene, diakinesis, and metaphase I. We inferred
      that the two mitotic chromosomes carrying 45S rDNA were homologous pairs.
      Considering the signals of 45S rDNA location during meiotic process, chromosome
      pairing of these two F1 hybrids was normal with an average pairing configuration
      of 2n=2x=20 (10 II). Our results indicated that 45S rDNA could provide a landmark
      for identification of individual chromosome during meiosis indirectly.

PMID- 19586898
TI  - [Improvement of the bilingual teaching of genetics using classic papers].
AB  - More and more colleges have recognized the importance of bilingual teaching in
      improvement students' capability to integrate the specialized knowledge with the
      foreign language. Bilingual teaching courses have been designed to enhance the
      innovation of high education and improve the culture quality of students.
      Genetics is one of the most important courses for undergraduate students majored
      in the region of life sciences. However, in the case of genetics, the advisable
      model to carry out bilingual teaching and the matter of great concern are
      ambiguous and need evidence accumulated by more teaching experiments. The classic
      papers in genetics are valuable resources to the bilingual teaching of genetics.
      This paper analyzed the role of classic papers in the bilingual teaching of
      genetics and discussed the methods for improving the bilingual teaching of
      genetics.

PMID- 19586897
TI  - [Construction and analysis of a forward and reverse subtractive cDNA library from
      leaves and stem of Polygonum sibiricum Laxm. under salt stress].
AB  - Using cDNAs prepared from the leaves and stems of Polygonum sibiricum Laxm.
      treated with NaHCO3 stress for 48 h as testers and cDNAs from unstressed P.
      sibiricum leaves and stems as drivers library, suppression subtractive
      hybridization (SSH) was employed to construct a cDNA subtracted library, which
      contained 2 282 valid sequences including 598 ESTs in the stems forward SSH
      library and 490 ESTs in the stem reverse SSH library, 627 ESTs in the leaf
      forward SSH library and 567 in the leaf reverse SSH library. According to the
      functional catalogue of MIPs and the comparison of the reverse and forward SSH
      libraries of the stem and leaf, the responses to NaHCO3 stress were different
      between leaf and stem, except for the same trend in cell rescue defense and
      transport facilitation. The trend in the metabolism, energy, photosynthesis,
      protein synthesis, transcription, and signal transduction was opposite. RT-PCR
      analysis demonstrated that the expression of 12 putative stress related genes in
      the NaHCO3-treated leaves and stems was different from that in the untreated
      leaves and stems. This indicated that different mechanisms might be responsible
      for reactions of leaf and stem in P. sibiricum. The results from this study are
      useful in understanding the molecular mechanism of saline-alkali tolerance in P.
      sibiricum.

PMID- 19586899
TI  - [A new SNP microarray technology based on single base extension].
AB  - Investigation of DNA-protein interactions is fundamental to understand the
      mechanism underlying a variety of life processes. In this article, various types
      of biochemical methods in DNA-protein interaction study in vivo and in vitro at
      the level of DNA, protein, and the complex, respectively were briefly reviewed.
      Traditional assays including Nitrocellulose filter-binding assay, Footprinting,
      EMSA, and Southwestern blotting were summarized. In addition, chromatin immunopre
      cipitation techniques including nChIP, xChIP, and ChIP-on-chip, which were widely
      used in epigenetics, were particularly introduced.

PMID- 19586900
TI  - Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated
      glucocorticoid receptor dephosphorylation.
AB  - Although glucocorticoids suppress proliferation of many cell types and are used
      in the treatment of certain cancers, trials of glucocorticoid therapy in breast
      cancer have been a disappointment. Another suggestion that estrogens may affect
      glucocorticoid action is that the course of some inflammatory diseases tends to
      be more severe and less responsive to corticosteroid treatment in females. To
      date, the molecular mechanism of cross-talk between estrogens and glucocorticoids
      is poorly understood. Here we show that, in both MCF-7 and T47D breast cancer
      cells, estrogen inhibits glucocorticoid induction of the MKP-1 (mitogen-activated
      protein kinase phosphatase-1) and serum/glucocorticoid-regulated kinase genes.
      Estrogen did not affect glucocorticoid-induced glucocorticoid receptor (GR)
      nuclear translocation but reduced ligand-induced GR phosphorylation at Ser-211,
      which is associated with the active form of GR. We show that estrogen increases
      expression of protein phosphatase 5 (PP5), which mediates the dephosphorylation
      of GR at Ser-211. Gene knockdown of PP5 abolished the estrogen-mediated
      suppression of GR phosphorylation and induction of MKP-1 and serum/glucocorticoid
      regulated kinase. More importantly, after PP5 knockdown estrogen-promoted cell
      proliferation was significantly suppressed by glucocorticoids. This study
      demonstrates cross-talk between estrogen-induced PP5 and GR action. It also
      reveals that PP5 inhibition may antagonize estrogen-promoted events in response
      to corticosteroid therapy.

PMID- 19586901
TI  - Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A.
AB  - The thrombin mutant W215A/E217A (WE) is a potent anticoagulant both in vitro and
      in vivo. Previous x-ray structural studies have shown that WE assumes a partially
      collapsed conformation that is similar to the inactive E* form, which explains
      its drastically reduced activity toward substrate. Whether this collapsed
      conformation is genuine, rather than the result of crystal packing or the
      mutation introduced in the critical 215-217 beta-strand, and whether binding of
      thrombomodulin to exosite I can allosterically shift the E* form to the active E
      form to restore activity toward protein C are issues of considerable mechanistic
      importance to improve the design of an anticoagulant thrombin mutant for
      therapeutic applications. Here we present four crystal structures of WE in the
      human and murine forms that confirm the collapsed conformation reported
      previously under different experimental conditions and crystal packing. We also
      present structures of human and murine WE bound to exosite I with a fragment of
      the platelet receptor PAR1, which is unable to shift WE to the E form. These
      structural findings, along with kinetic and calorimetry data, indicate that WE is
      strongly stabilized in the E* form and explain why binding of ligands to exosite
      I has only a modest effect on the E*-E equilibrium for this mutant. The E* --> E
      transition requires the combined binding of thrombomodulin and protein C and
      restores activity of the mutant WE in the anticoagulant pathway.

PMID- 19586902
TI  - Interaction of the RhoA exchange factor Net1 with discs large homolog 1 protects
      it from proteasome-mediated degradation and potentiates Net1 activity.
AB  - Net1 is a nuclear Rho guanine nucleotide exchange factor that is specific for the
      RhoA subfamily of small G proteins. Truncated forms of Net1 are transforming in
      NIH3T3 cells, and this activity requires cytoplasmic localization of Net1 as well
      as the presence of a COOH-terminal PDZ binding site. We have previously shown
      that Net1 interacts with PDZ domain-containing proteins within the Discs Large
      (Dlg) family and relocalizes them to the nucleus. In the present work, we
      demonstrate that Net1 binds directly to the first two PDZ domains of Dlg1 and
      that both PDZ domains are required for maximal interaction in cells. Furthermore,
      we show that Net1 is an unstable protein in MCF7 breast epithelial cells and that
      interaction with Dlg1 significantly enhances Net1 stability. Stabilization by
      Dlg1 significantly increases the ability of Net1 to stimulate RhoA activation in
      cells. The stability of endogenous Net1 is strongly enhanced by cell-cell
      contact, and this correlates with a dramatic increase in the interaction between
      Net1 and Dlg1. Importantly, disruption of E-cadherin-mediated cell contacts,
      either by depletion of external calcium or by treatment with transforming growth
      factor beta, leads to a rapid loss of the interaction between Net1 and Dlg1 and a
      subsequent increase in the ubiquitylation of Net1. These results indicate that
      Net1 requires interaction with PDZ domain proteins, such as Dlg1, to protect it
      from proteasome-mediated degradation and to maximally stimulate RhoA and that
      this interaction is regulated by cell-cell contact.

PMID- 19586903
TI  - The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear
      export receptor NXF1.
AB  - The human SPEN family proteins SHARP, RBM15/OTT1, and RBM15B/OTT3 share the
      structural domain architecture but show distinct functional properties. Here, we
      examined the function of OTT3 and compared it with its paralogues RBM15 and
      SHARP. We found that OTT3, like RBM15, has post-transcriptional regulatory
      activity, whereas SHARP does not, supporting a divergent role of RBM15 and OTT3.
      OTT3 shares with RBM15 the association with the splicing factor compartment and
      the nuclear envelope as well as the binding to mRNA export factors NXF1 and
      Aly/REF. Mutational analysis revealed direct interaction of OTT3 and RBM15 with
      NXF1 via their C-terminal regions. Biochemical and subcellular localization
      studies showed that OTT3 and RBM15 also interact with each other in vivo, further
      supporting a shared function. Genetic knockdown of RBM15 in mouse is
      embryonically lethal, indicating that OTT3 cannot compensate for the RBM15 loss,
      which supports the notion that these proteins, in addition to sharing similar
      activities, likely have distinct biological roles.

PMID- 19586904
TI  - The role of nitric-oxide synthase in the regulation of UVB light-induced
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2.
AB  - UV light induces phosphorylation of the alpha subunit of the eukaryotic
      initiation factor 2 (eIF2alpha) and inhibits global protein synthesis. Both eIF2
      kinases, protein kinase-like endoplasmic reticulum kinase (PERK) and general
      control of nonderepressible protein kinase 2 (GCN2), have been shown to
      phosphorylate eIF2alpha in response to UV irradiation. However, the roles of PERK
      and GCN2 in UV-induced eIF2alpha phosphorylation are controversial. The one or
      more upstream signaling pathways that lead to the activation of PERK or GCN2
      remain unknown. In this report we provide data showing that both PERK and GCN2
      contribute to UV-induced eIF2alpha phosphorylation in human keratinocyte (HaCaT)
      and mouse embryonic fibroblast cells. Reduction of expression of PERK or GCN2 by
      small interfering RNA decreases phosphorylation of eIF2alpha after UV
      irradiation. These data also show that nitric-oxide synthase (NOS)-mediated
      oxidative stress plays a role in regulation of eIF2alpha phosphorylation upon UV
      irradiation. Treating the cells with the broad NOS inhibitor N(G)-methyl-l
      arginine, the free radical scavenger N-acetyl-l-cysteine, or the NOS substrate l
      arginine partially inhibits UV-induced eIF2alpha phosphorylation. The results
      presented above led us to propose that NOS mediates UV-induced eIF2alpha
      phosphorylation by activation of both PERK and GCN2 via oxidative stress and l
      arginine starvation signaling pathways.

PMID- 19586905
TI  - Slc4a11 gene disruption in mice: cellular targets of sensorineuronal
      abnormalities.
AB  - NaBC1 (the SLC4A11 gene) belongs to the SLC4 family of sodium-coupled bicarbonate
      (carbonate) transporter proteins and functions as an electrogenic sodium borate
      cotransporter. Mutations in SLC4A11 cause either corneal abnormalities (corneal
      hereditary dystrophy type 2) or a combined auditory and visual impairment
      (Harboyan syndrome). The role of NaBC1 in sensory systems is poorly understood,
      given the difficulty of studying patients with NaBC1 mutations. We report our
      findings in Slc4a11(-/-) mice generated to investigate the role of NaBC1 in
      sensorineural systems. In wild-type mice, specific NaBC1 immunoreactivity was
      detected in fibrocytes of the spiral ligament, from the basal to the apical
      portion of the cochlea. NaBC1 immunoreactivity was present in the vestibular
      labyrinth, in stromal cells underneath the non-immunoreactive sensory epithelia
      of the macula utricle, sacule, and crista ampullaris, and the membranous
      vestibular labyrinth was collapsed. Both auditory brain response and vestibular
      evoked potential waveforms were significantly abnormal in Slc4a11(-/-) mice. In
      the cornea, NaBC1 was highly expressed in the endothelial cell layer with less
      staining in epithelial cells. However, unlike humans, the corneal phenotype was
      mild with a normal slit lamp evaluation. Corneal endothelial cells were
      morphologically normal; however, both the absolute height of the corneal basal
      epithelial cells and the relative basal epithelial cell/total corneal thickness
      were significantly increased in Slc4a11(-/-) mice. Our results demonstrate for
      the first time the importance of NaBC1 in the audio-vestibular system and provide
      support for the hypothesis that SLC4A11 should be considered a potential
      candidate gene in patients with isolated sensorineural vestibular hearing
      abnormalities.

PMID- 19586906
TI  - Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and
      protects endotoxin-induced epithelial barrier disruption and lung injury.
AB  - Lysophosphatidic acid (LPA), a bioactive phospholipid, induces a wide range of
      cellular effects, including gene expression, cytoskeletal rearrangement, and cell
      survival. We have previously shown that LPA stimulates secretion of pro- and anti
      inflammatory cytokines in bronchial epithelial cells. This study provides
      evidence that LPA enhances pulmonary epithelial barrier integrity through protein
      kinase C (PKC) delta- and zeta-mediated E-cadherin accumulation at cell-cell
      junctions. Treatment of human bronchial epithelial cells (HBEpCs) with LPA
      increased transepithelial electrical resistance (TER) by approximately 2.0-fold
      and enhanced accumulation of E-cadherin to the cell-cell junctions through
      Galpha(i)-coupled LPA receptors. Knockdown of E-cadherin with E-cadherin small
      interfering RNA or pretreatment with EGTA (0.1 mm) prior to LPA (1 microm)
      treatment attenuated LPA-induced increases in TER in HBEpCs. Furthermore, LPA
      induced tyrosine phosphorylation of focal adhesion kinase (FAK) and
      overexpression of the FAK inhibitor, and FAK-related non-kinase-attenuated LPA
      induced increases in TER and E-cadherin accumulation at cell-cell junctions.
      Overexpression of dominant negative protein kinase delta and zeta attenuated LPA
      induced phosphorylation of FAK, accumulation of E-cadherin at cell-cell
      junctions, and an increase in TER. Additionally, lipopolysaccharide decreased TER
      and induced E-cadherin relocalization from cell-cell junctions to cytoplasm in a
      dose-dependent fashion, which was restored by LPA post-treatment in HBEpCs.
      Intratracheal post-treatment with LPA (5 microm) reduced LPS-induced neutrophil
      influx, protein leak, and E-cadherin shedding in bronchoalveolar lavage fluids in
      a murine model of acute lung injury. These data suggest a protective role of LPA
      in airway inflammation and remodeling.

PMID- 19586907
TI  - Structural and inhibition analysis reveals the mechanism of selectivity of a
      series of aggrecanase inhibitors.
AB  - Several inhibitors of a series of cis-1(S)2(R)-amino-2-indanol-based compounds
      were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other
      metalloproteases. To understand the nature of this selectivity for aggrecanases,
      the inhibitors, along with the broad spectrum metalloprotease inhibitor
      marimastat, were independently bound to the catalytic domain of ADAMTS-5, and the
      corresponding crystal structures were determined. By comparing the structures, it
      was determined that the specificity of the relative inhibitors for ADAMTS-5 was
      not driven by a specific interaction, such as zinc chelation, hydrogen bonding,
      or charge interactions, but rather by subtle and indirect factors, such as water
      bridging, ring rigidity, pocket size, and shape, as well as protein conformation
      flexibility.

PMID- 19586908
TI  - Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA
      damage via physical interaction with xeroderma pigmentosum group A.
AB  - In response to DNA damage, eukaryotic cells activate a series of DNA damage
      dependent pathways that serve to arrest cell cycle progression and remove DNA
      damage. Coordination of cell cycle arrest and damage repair is critical for
      maintenance of genomic stability. However, this process is still poorly
      understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle
      checkpoint are the major pathways responsible for repair of UV-induced DNA
      damage. Here we show that ATR physically interacts with the NER factor Xeroderma
      pigmentosum group A (XPA). Using a mass spectrometry-based protein footprinting
      method, we found that ATR interacts with a helix-turn-helix motif in the minimal
      DNA-binding domain of XPA where an ATR phosphorylation site (serine 196) is
      located. XPA-deficient cells complemented with XPA containing a point mutation of
      S196A displayed a reduced repair efficiency of cyclobutane pyrimidine dimers as
      compared with cells complemented with wild-type XPA, although no effect was
      observed for repair of (6-4) photoproducts. This suggests that the ATR-dependent
      phosphorylation of XPA may promote NER repair of persistent DNA damage. In
      addition, a K188A point mutation of XPA that disrupts the ATR-XPA interaction
      inhibits the nuclear import of XPA after UV irradiation and, thus, significantly
      reduced DNA repair efficiency. By contrast, the S196A mutation has no effect on
      XPA nuclear translocation. Taken together, our results suggest that the ATR-XPA
      interaction mediated by the helix-turn-helix motif of XPA plays an important role
      in DNA-damage responses to promote cell survival and genomic stability after UV
      irradiation.

PMID- 19586909
TI  - Endogenous human CaMKII inhibitory protein suppresses tumor growth by inducing
      cell cycle arrest and apoptosis through down-regulation of the
      phosphatidylinositide 3-kinase/Akt/HDM2 pathway.
AB  - Inhibition of calcium/calmodulin-dependent protein kinase II (CaMKII) results in
      hypophosphorylation of CaMKII substrates and in some cases suppresses cell
      growth. We previously presented the first report of the human CaMKII inhibitory
      protein, hCaMKIINbeta. Here we report the functional characterization of
      hCaMKIINbeta in ovarian cancer cells. We showed that hCaMKIINbeta was highly
      expressed in normal ovarian tissues but was not detected in human ovarian
      adenocarcinoma, indicating that decreased expression of hCaMKIINbeta may be
      involved in the pathogenesis of human ovarian adenocarcinoma. As an endogenous
      CaMKII inhibitor, hCaMKIINbeta could significantly inhibit the growth of human
      ovarian cancer cells in vitro. In vivo, hCaMKIINbeta decreased the tumorigenicity
      and growth of HO-8910PM human ovarian cancer cells and prolonged the survival of
      tumor-bearing mice. hCaMKIINbeta blocked cell cycle progression and induced
      apoptosis of HO-8910PM cells, which was correlated with the up-regulation of p21,
      p53, and Bax and the down-regulation of cyclin A, cyclin D1, cyclin E, CDK2,
      phosphorylated retinoblastoma, and Bcl-2. We further demonstrated that
      hCaMKIINbeta-mediated CaMKII inhibition suppressed Akt activation, leading to the
      down-regulation of HDM2, which was responsible for the up-regulation of p53 and
      p21 in human ovarian cancer cells. The tumor-suppressive effect and the negative
      expression in human ovarian cancer tissues suggest that hCaMKIINbeta may play an
      important role in the regulation of tumor cell growth, possibly contributing to
      the development of new therapeutic strategies for ovarian cancer.

PMID- 19586910
TI  - Crystal structures of the reduced, sulfenic acid, and mixed disulfide forms of
      SarZ, a redox active global regulator in Staphylococcus aureus.
AB  - SarZ is a global transcriptional regulator that uses a single cysteine residue,
      Cys(13), to sense peroxide stress and control metabolic switching and virulence
      in Staphylococcus aureus. SarZ belongs to the single-cysteine class of OhrR-MgrA
      proteins that play key roles in oxidative resistance and virulence regulation in
      various bacteria. We present the crystal structures of the reduced form, sulfenic
      acid form, and mixed disulfide form of SarZ. Both the sulfenic acid and mixed
      disulfide forms are structurally characterized for the first time for this class
      of proteins. The Cys(13) sulfenic acid modification is stabilized through two
      hydrogen bonds with surrounding residues, and the overall DNA-binding
      conformation is retained. A further reaction of the Cys(13) sulfenic acid with an
      external thiol leads to formation of a mixed disulfide bond, which results in an
      allosteric change in the DNA-binding domains, disrupting DNA binding. Thus, the
      crystal structures of SarZ in three different states provide molecular level
      pictures delineating the mechanism by which this class of redox active regulators
      undergoes activation. These structures help to understand redox-mediated
      virulence regulation in S. aureus and activation of the MarR family proteins in
      general.

PMID- 19586911
TI  - The flexible motif V of Epstein-Barr virus deoxyuridine 5'-triphosphate
      pyrophosphatase is essential for catalysis.
AB  - Deoxyuridine 5'-triphosphate pyrophosphatases (dUTPases) are ubiquitous enzymes
      essential for hydrolysis of dUTP, thus preventing its incorporation into DNA.
      Although Epstein-Barr virus (EBV) dUTPase is monomeric, it has a high degree of
      similarity with the more frequent trimeric form of the enzyme. In both cases, the
      active site is composed of five conserved sequence motifs. Structural and
      functional studies of mutants based on the structure of EBV dUTPase gave new
      insight into the mechanism of the enzyme. A first mutant allowed us to exclude a
      role in enzymatic activity for the disulfide bridge involving the beginning of
      the disordered C terminus. Sequence alignments revealed two groups of dUTPases,
      based on the position in sequence of a conserved aspartic acid residue close to
      the active site. Single mutants of this residue in EBV dUTPase showed a highly
      impaired catalytic activity, which could be partially restored by a second
      mutation, making EBV dUTPase more similar to the second group of enzymes.
      Deletion of the flexible C-terminal tail carrying motif V resulted in a protein
      completely devoid of enzymatic activity, crystallizing with unhydrolyzed Mg(2+)
      dUTP complex in the active site. Point mutations inside motif V highlighted the
      essential role of lid residue Phe(273). Magnesium appears to play a role mainly
      in substrate binding, since in absence of Mg(2+), the K(m) of the enzyme is
      reduced, whereas the k(cat) is less affected.

PMID- 19586912
TI  - Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains
      with Hsp70 and Hsp90: computational analysis and protein engineering.
AB  - The Hsp-organizing protein (HOP) binds to the C termini of the chaperones Hsp70
      and Hsp90, thus bringing them together so that substrate proteins can be passed
      from Hsp70 to Hsp90. Because Hsp90 is essential for the correct folding and
      maturation of many oncogenic proteins, it has become a significant target for
      anti-cancer drug design. HOP binds to Hsp70 and Hsp90 via two independent
      tetratricopeptide (TPR) domains, TPR1 and TPR2A, respectively. We have analyzed
      ligand binding using Poisson-Boltzmann continuum electrostatic calculations, free
      energy perturbation, molecular dynamics simulations, and site-directed
      mutagenesis to delineate the contribution of different interactions to the
      affinity and specificity of the TPR-peptide interactions. We found that continuum
      electrostatic calculations could be used to guide protein design by removing
      unfavorable interactions to increase binding affinity, with an 80-fold increase
      in affinity for TPR2A. Contributions at buried charged residues, however, were
      better predicted by free energy perturbation calculations. We suggest using a
      combination of the two approaches for increasing the accuracy of results, with
      free energy perturbation calculations used only at selected buried residues of
      the ligand binding pocket. Finally we present the crystal structure of TPR2A in
      complex with its non-cognate Hsp70 ligand, which provides insight on the origins
      of specificity in TPR domain-peptide recognition.

PMID- 19586913
TI  - Demonstration of proton-coupled electron transfer in the copper-containing
      nitrite reductases.
AB  - The reduction of nitrite (NO2-) into nitric oxide (NO), catalyzed by nitrite
      reductase, is an important reaction in the denitrification pathway. In this
      study, the catalytic mechanism of the copper-containing nitrite reductase from
      Alcaligenes xylosoxidans (AxNiR) has been studied using single and multiple
      turnover experiments at pH 7.0 and is shown to involve two protons. A novel
      steady-state assay was developed, in which deoxyhemoglobin was employed as an NO
      scavenger. A moderate solvent kinetic isotope effect (SKIE) of 1.3 +/- 0.1
      indicated the involvement of one protonation to the rate-limiting catalytic step.
      Laser photoexcitation experiments have been used to obtain single turnover data
      in H2O and D2O, which report on steps kinetically linked to inter-copper electron
      transfer (ET). In the absence of nitrite, a normal SKIE of approximately 1.33 +/-
      0.05 was obtained, suggesting a protonation event that is kinetically linked to
      ET in substrate-free AxNiR. A nitrite titration gave a normal hyperbolic behavior
      for the deuterated sample. However, in H2O an unusual decrease in rate was
      observed at low nitrite concentrations followed by a subsequent acceleration in
      rate at nitrite concentrations of >10 mM. As a consequence, the observed ET
      process was faster in D2O than in H2O above 0.1 mM nitrite, resulting in an
      inverted SKIE, which featured a significant dependence on the substrate
      concentration with a minimum value of approximately 0.61 +/- 0.02 between 3 and
      10 mM. Our work provides the first experimental demonstration of proton-coupled
      electron transfer in both the resting and substrate-bound AxNiR, and two protons
      were found to be involved in turnover.

PMID- 19586914
TI  - Two D-2-hydroxy-acid dehydrogenases in Arabidopsis thaliana with catalytic
      capacities to participate in the last reactions of the methylglyoxal and beta
      oxidation pathways.
AB  - The Arabidopsis thaliana locus At5g06580 encodes an ortholog to Saccharomyces
      cerevisiae d-lactate dehydrogenase (AtD-LDH). The recombinant protein is a
      homodimer of 59-kDa subunits with one FAD per monomer. A substrate screen
      indicated that AtD-LDH catalyzes the oxidation of d- and l-lactate, d-2
      hydroxybutyrate, glycerate, and glycolate using cytochrome c as an electron
      acceptor. AtD-LDH shows a clear preference for d-lactate, with a catalytic
      efficiency 200- and 2000-fold higher than that for l-lactate and glycolate,
      respectively, and a K(m) value for d-lactate of approximately 160 microm. Knock
      out mutants showed impaired growth in the presence of d-lactate or methylglyoxal.
      Collectively, the data indicated that the protein is a d-LDH that participates in
      planta in the methylglyoxal pathway. Web-based bioinformatic tools revealed the
      existence of a paralogous protein encoded by locus At4g36400. The recombinant
      protein is a homodimer of 61-kDa subunits with one FAD per monomer. A substrate
      screening revealed highly specific d-2-hydroxyglutarate (d-2HG) conversion in the
      presence of an organic cofactor with a K(m) value of approximately 580 microm.
      Thus, the enzyme was characterized as a d-2HG dehydrogenase (AtD-2HGDH). Analysis
      of knock-out mutants demonstrated that AtD-2HGDH is responsible for the total d
      2HGDH activity present in A. thaliana. Gene coexpression analysis indicated that
      AtD-2HGDH is in the same network as several genes involved in beta-oxidation and
      degradation of branched-chain amino acids and chlorophyll. It is proposed that
      AtD-2HGDH participates in the catabolism of d-2HG most probably during the
      mobilization of alternative substrates from proteolysis and/or lipid degradation.

PMID- 19586915
TI  - The hexosamine biosynthesis pathway is essential for pancreatic beta cell
      development.
AB  - Pancreatic exocrine and endocrine cells develop during embryonic life from
      endodermal progenitors. This process depends on activation of a hierarchy of
      transcription factors. Although information is available regarding the mesodermal
      signals controlling pancreas development, little is known about the role of
      environmental factors such as nutrients, including glucose, that also may impact
      development. Previously, we showed that glucose plays an important and specific
      role in beta cell development by activating the transition of Neurogenin3
      positive endocrine progenitors into beta cells. Here, we examined the implication
      of glucose metabolism and more precisely the role of the hexosamine biosynthesis
      pathway (HBP) to understand the mechanisms by which glucose regulates beta cell
      development. We have established an in vitro model of endocrine and exocrine
      cells development from embryonic day 13.5 rat pancreases in a manner that
      replicates in vivo pancreas development perfectly. Using this model, we tested
      the effect of selective inhibitors and activators of the HBP and found that the
      HBP has a modest effect on cell proliferation and exocrine cell differentiation.
      On the other hand, beta cell development is tightly controlled by the HBP.
      Specifically, HBP activators increase beta cell development, whereas inhibitors
      repress such development. Importantly, both the HBP and glucose control the same
      steps in beta cell development.

PMID- 19586917
TI  - Beta1 integrin deficiency results in multiple abnormalities of the knee joint.
AB  - The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia
      associated with high mortality rate around birth. To assess the impact of beta1
      integrin-mediated cell-matrix interactions on the function of adult knee joints,
      we conditionally deleted the beta1 integrin gene in early limb mesenchyme using
      the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint
      defects due to beta1 integrin deficiency in articular regions. The articular
      cartilage (AC) was structurally disorganized, accompanied by accelerated terminal
      differentiation, altered shape, and disrupted actin cytoskeleton of the
      chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival
      resulted in hypocellularity. However, no significant differences in cartilage
      erosion, in the expression of matrix-degrading proteases, or in the exposure of
      aggrecan and collagen II cleavage neoepitopes were observed between control and
      mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38,
      and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and
      MMP-13 expression were indistinguishable in control and mutant femoral head
      explants. The mutant synovium was hyperplastic and frequently underwent
      chondrogenic differentiation. beta1-null synoviocytes showed increased
      proliferation and phospho-focal adhesion kinase expression. Taken together,
      deletion of beta1 integrins in the limb bud results in multiple abnormalities of
      the knee joints; however, it does not accelerate AC destruction, perturb
      cartilage metabolism, or influence intracellular MAPK signaling pathways.

PMID- 19586918
TI  - Distinct structural requirements for interleukin-4 (IL-4) and IL-13 binding to
      the shared IL-13 receptor facilitate cellular tuning of cytokine responsiveness.
AB  - Both interleukin-4 (IL-4) and IL-13 can bind to the shared receptor composed of
      the IL-4 receptor alpha chain and the IL-13 receptor alpha1 chain (IL-13Ralpha1);
      however, the mechanisms by which these ligands bind to the receptor chains are
      different, enabling the principal functions of these ligands to be different. We
      have previously shown that the N-terminal Ig-like domain in IL-13Ralpha1, called
      the D1 domain, is the specific and critical binding unit for IL-13. However, it
      has still remained obscure which amino acid has specific binding capacity to IL
      13 and why the D1 domain acts as the binding site for IL-13, but not IL-4. To
      address these questions, in this study we performed mutational analyses for the
      D1 domain, combining the structural data to identify the amino acids critical for
      binding to IL-13. Mutations of Lys-76, Lys-77, or Ile-78 in c' strand in which
      the crystal structure showed interaction with IL-13, and those of Trp-65 and Ala
      79 adjacent to the interacting site, resulted in significant impairment of IL-13
      binding, demonstrating that these amino acids generate the binding site.
      Furthermore, mutations of Val-35, Leu-38, or Val-42 at the N-terminal beta-strand
      also resulted in loss of IL-13 binding, probably from decreased structural
      stability. None of the mutations employed here affected IL-4 binding. These
      results demonstrate that the D1 domain of IL-13Ralpha1 acts as an affinity
      converter, through direct cytokine interactions, that allows the shared receptor
      to respond differentially to IL-4 and IL-13.

PMID- 19586916
TI  - Pattern of expression and substrate specificity of chloroplast ferredoxins from
      Chlamydomonas reinhardtii.
AB  - Ferredoxin (Fd) is the major iron-containing protein in photosynthetic organisms
      and is central to reductive metabolism in the chloroplast. The Chlamydomonas
      reinhardtii genome encodes six plant type [Fe2S2] ferredoxins, products of PETF,
      FDX2-FDX6. We performed the functional analysis of these ferredoxins by
      localizing Fd, Fdx2, Fdx3, and Fdx6 to the chloroplast by using isoform-specific
      antibodies and monitoring the pattern of gene expression by iron and copper
      nutrition, nitrogen source, and hydrogen peroxide stress. In addition, we also
      measured the midpoint redox potentials of Fd and Fdx2 and determined the kinetic
      parameters of their reactions with several ferredoxin-interacting proteins,
      namely nitrite reductase, Fd:NADP+ oxidoreductase, and Fd:thioredoxin reductase.
      We found that each of the FDX genes is differently regulated in response to
      changes in nutrient supply. Moreover, we show that Fdx2 (Em = -321 mV), whose
      expression is regulated by nitrate, is a more efficient electron donor to nitrite
      reductase relative to Fd. Overall, the results suggest that each ferredoxin
      isoform has substrate specificity and that the presence of multiple ferredoxin
      isoforms allows for the allocation of reducing power to specific metabolic
      pathways in the chloroplast under various growth conditions.

PMID- 19586919
TI  - Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1.
AB  - Regulation by the NK and T cell surface receptor CD244 in mice and humans depends
      both on engagement at the cell surface by CD48 and intracellular interactions
      with SAP and EAT-2. Relevance to human disease by manipulating CD244 in mouse
      models is complicated by rodent CD2 also binding CD48. We distinguish between
      contributions of mouse CD244 and CD2 on engagement of CD48 in a mouse T cell
      hybridoma. CD2 and CD244 both contribute positively to the immune response as
      mutation of proline-rich motifs or tyrosine motifs in the tails of CD2 and CD244,
      respectively, result in a decrease in antigen-specific interleukin-2 production.
      Inhibitory effects of mouse CD244 are accounted for by competition with CD2 at
      the cell surface for CD48. In humans CD2 and CD244 are engaged separately at the
      cell surface but biochemical data suggest a potential conserved intracellular
      link between the two receptors through FYN kinase. We identify a novel signaling
      mechanism for CD244 through its potential to recruit phospholipase C-gamma1 via
      the conserved phosphorylated tyrosine motif in the tail of the adaptor protein
      EAT-2, which we show is important for function.

PMID- 19586920
TI  - B cell antigen receptor endocytosis and antigen presentation to T cells require
      Vav and dynamin.
AB  - Antigen binding to the B cell antigen receptor (BCR) initiates an array of
      signaling events. These include endocytosis of ligand-receptor complexes via
      clathrin-coated pits, trafficking of the internalized ligand to lysosomes,
      degradation of the associated proteins to peptides, and peptide presentation on
      nascent major histocompatibility complex class II to T cells. The signal
      transduction events supporting BCR internalization are not well understood. We
      have identified a pathway supporting BCR internalization that includes the Vav1
      and/or Vav3 isoforms and the GTPase dynamin. Vav1 and -3 are not required for B
      cell development and maturation, nor for a variety of BCR-induced signaling
      events nor for BCR signaling leading to major histocompatibility complex class II
      and CD80 expression, but Vav1 and/or -3 are absolutely required for BCR
      endocytosis and BCR-induced Rac-GTP loading. This is the first demonstration of a
      link between Vav and Rac in BCR internalization leading to antigen presentation
      to T cells.

PMID- 19586921
TI  - The right to choose: multiple pathways for activating copper,zinc superoxide
      dismutase.
AB  - Since the discovery of SOD1 in 1969, there have been numerous achievements made
      in our understanding of the enzyme's biochemical reactivity and its role in
      oxidative stress protection and as a genetic determinant in amyotrophic lateral
      sclerosis. Many recent advances have also been made in understanding the
      "activation" of SOD1, i.e. the process by which an inert polypeptide is converted
      to a mature active enzyme through post-translational modifications. To date, two
      such activation pathways have been identified: one requiring the CCS copper
      chaperone and one that works independently of CCS to insert copper and activate
      SOD1 through oxidation of an intramolecular disulfide. Depending on an organism's
      lifestyle and complexity, different eukaryotes have evolved to favor one pathway
      over the other. Some organisms rely solely on CCS for activating SOD1, and others
      can only activate SOD1 independently of CCS, whereas the majority of eukaryotes
      appear to have evolved to use both pathways. In this minireview, we shall
      highlight recent advances made in understanding the mechanisms by which the CCS
      dependent and CCS-independent pathways control the activity, structure, and
      intracellular localization of copper,zinc superoxide dismutase, with relevance to
      amyotrophic lateral sclerosis and an emphasis on evolutionary biology.

PMID- 19586923
TI  - A functional genetic study identifies HAND1 mutations in septation defects of the
      human heart.
AB  - Heart and neural crest derivatives expressed 1 (HAND1) is a basic helix-loop
      helix (bHLH) transcription factor essential for mammalian heart development.
      Absence of Hand1 in mice results in embryonal lethality, as well as in a wide
      spectrum of cardiac abnormalities including failed cardiac looping, defective
      chamber septation and impaired ventricular development. Therefore, Hand1 is a
      strong candidate for the many cardiac malformations observed in human congenital
      heart disease (CHD). Recently, we identified a loss-of-function frameshift
      mutation (p.A126fs) in the bHLH domain of HAND1 frequent in hypoplastic hearts.
      This finding prompted us to continue our search for HAND1 gene mutations in a
      different cohort of malformed hearts affected primarily by septation defects.
      Indeed, in tissue samples of septal defects, we detected 32 sequence alterations
      leading to amino acid change, of which 12 are in the bHLH domain of HAND1.
      Interestingly, 10 sequence alterations, such as p.L28H and p.L138P, had been
      identified earlier in hypoplastic hearts, but the frequent p.A126fs mutation was
      absent except in one aborted case with ventricular septal defect and outflow
      tract abnormalities. Functional studies in yeast and mammalian cells enabled
      translation of sequence alterations to HAND1 transcriptional activity, which was
      reduced or abolished by certain mutations, notably p.L138P. Our results suggest
      that HAND1 may also be affected in septation defects of the human hearts, and
      thus has a broader role in human heart development and CHD.

PMID- 19586922
TI  - Inactive X chromosome-specific reduction in placental DNA methylation.
AB  - Genome-wide levels of DNA methylation vary between tissues, and compared with
      other tissues, the placenta has been reported to demonstrate a global decrease in
      methylation as well as decreased methylation of X-linked promoters. Methylation
      is one of many features that differentiate the active and inactive X, and it is
      well established that CpG island promoters on the inactive X are hypermethylated.
      We now report a detailed analysis of methylation at different regions across the
      X in male and female placenta and blood. A significant (P < 0.001) placental
      hypomethylation of LINE1 elements was observed in both males and females.
      Relative to blood placental promoter hypomethylation was only observed for X
      linked, not autosomal promoters, and was significant for females (P < 0.0001) not
      males (P = 0.9266). In blood, X-linked CpG island promoters were shown to have
      moderate female methylation (66% across 70 assays) and low (23%) methylation in
      males. A similar methylation pattern in blood was observed for approximately 20%
      of non-island promoters as well as 50% of the intergenic or intragenic CpG
      islands, the latter is likely due to the presence of unannotated promoters. Both
      intragenic and intergenic regions showed similarly high methylation levels in
      male and female blood (68 and 66%) while placental methylation of these regions
      was lower, particularly in females. Thus placental hypomethylation relative to
      blood is observed globally at repetitive elements as well as across the X. The
      decrease in X-linked placental methylation is consistently greater in females
      than males and implicates an inactive X specific loss of methylation in the
      placenta.

PMID- 19586925
TI  - A paediatric palliative care programme in development: trends in referral and
      location of death.
AB  - PURPOSE: To describe the formation of a paediatric palliative care programme
      providing care in hospital, at home or in hospice, ensuring continuity of care
      where the child and family desire. STUDY DESIGN: Descriptive analysis was
      performed on referral source, diagnosis and reason for discharge for patients
      referred to the Palliative Care Team at the Children's Hospital of Eastern
      Ontario in Ottawa, Ontario, Canada from 1999 to 2007. RESULTS: 341 children were
      referred. 24% had a neurological condition, 21% had genetic disorders or
      congenital anomalies, 20% had cancer, 18% had metabolic or neurodegenerative
      conditions and 17% had another diagnosis. The major sources of referral included
      paediatricians, neonatologists, oncologists and intensivists. 55% of the children
      have died. 58% of these died in hospital, 27% at home and 15% in hospice. Of the
      remaining 152 children, 7% were discharged from the programme after clinical
      improvement, 4% were moved to another geographic location or an adult centre, 2%
      were not eligible, 1% declined services and 4% were lost to follow-up. The
      remaining 90 children continue to be followed-up. In the hospitalised patients
      who died, the annual referral rate increased from 20% to >50%. IMPLICATIONS:
      Referral to the palliative care team has increased over time in all diagnostic
      categories and from all sources. Most children died in hospital; however, a
      significant number of families chose end-of-life care at home or in a hospice.

PMID- 19586926
TI  - Child health in Colombia.
AB  - Colombia is a country with major problems, mainly a high degree of inequality and
      an unacceptably high level of violence (both armed military conflict and crime
      related). There are unacceptably high variations in health and health provision.
      Despite these difficulties, there are important steps being taken by both the
      government and independent organisations to try and improve child health and to
      achieve the Millennium Development Goals in relation to poverty, hunger and
      health issues. The participation of different sectors and stakeholders (including
      government, non-governmental organisations and other organisations of civil
      society) is essential to overcome Colombian history and to promote a better place
      for children.

PMID- 19586927
TI  - Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic
      migraine: implications for diagnostic testing.
AB  - BACKGROUND: Episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1
      (FHM1) are autosomal dominant disorders characterised by paroxysmal ataxia and
      migraine, respectively. Point mutations in CACNA1A, which encodes the neuronal
      P/Q-type calcium channel, have been detected in many cases of EA2 and FHM1. The
      genetic basis of typical cases without CACNA1A point mutations is not fully
      known. Standard DNA sequencing methods may miss large scale genetic
      rearrangements such as deletions and duplications. The authors investigated
      whether large scale genetic rearrangements in CACNA1A can cause EA2 and FHM1.
      METHODS: The authors used multiplex ligation dependent probe amplification (MLPA)
      to screen for intragenic CACNA1A rearrangements. RESULTS: The authors identified
      five previously unreported large scale deletions in CACNA1A in seven families
      with episodic ataxia and in one case with hemiplegic migraine. One of the
      deletions (exon 6 of CACNA1A) segregated with episodic ataxia in a four
      generation family with eight affected individuals previously mapped to 19p13. In
      addition, the authors identified the first pathogenic duplication in CACNA1A in
      an index case with isolated episodic diplopia without ataxia and in a first
      degree relative with episodic ataxia. CONCLUSIONS: Large scale deletions and
      duplications can cause CACNA1A associated channelopathies. Direct DNA sequencing
      alone is not sufficient as a diagnostic screening test.

PMID- 19586929
TI  - Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome.
AB  - BACKGROUND: Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly
      variable, X-linked dominant syndrome with abnormalities of ectodermal and
      mesodermal origin. In 2007, mutations in the PORCN gene were found to be
      causative in Goltz-Gorlin syndrome. METHOD: A series of 17 patients with Goltz
      Gorlin syndrome is reported on, and their phenotype and genotype are described.
      RESULTS: In 14 patients (13 females and one male), a PORCN mutation was found.
      Mutations included nonsense (n = 5), frameshift (n = 2), aberrant splicing (n =
      2) and missense (n = 5) mutations. No genotype-phenotype correlation was found.
      All patients with the classical features of the syndrome had a detectable
      mutation. In three females with atypical signs, no mutation was found. The male
      patient had classical features and showed mosaicism for a PORCN nonsense mutation
      in fibroblasts. Two affected sisters had a mutation not detectable in their
      parents, supporting germline mosaicism. Their father had undergone radiation for
      testicular cancer in the past. Two classically affected females had three
      severely affected female fetuses which all had midline thoracic and abdominal
      wall defects, resembling the pentalogy of Cantrell and the limb-body wall
      complex. Thoracic and abdominal wall defects were also present in two surviving
      patients. PORCN mutations can possibly cause pentalogy of Cantrell and limb-body
      wall complexes as well. Therefore, particularly in cases with limb defects, it
      seems useful to search for these. CONCLUSIONS: PORCN mutations can be found in
      all classically affected cases of Goltz-Gorlin syndrome, including males. Somatic
      and germline mosaicism occur. There is no evident genotype-phenotype correlation.

PMID- 19586928
TI  - Admixture mapping of ankle-arm index: identification of a candidate locus
      associated with peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is associated with significant
      morbidity and mortality, and has a higher prevalence in African Americans than
      Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the
      leg to that in the arm, and, when low, is a marker of PAD. METHODS: The authors
      used an admixture mapping approach to search for genetic loci associated with low
      AAI. Using data from 1040 African American participants in the observational,
      population based Health, Aging, and Body Composition Study who were genotyped at
      1322 single nucleotide polymorphisms (SNPs) that are informative for African
      versus European ancestry and span the entire genome, we estimated genetic
      ancestry in each chromosomal region and then tested the association between AAI
      and genetic ancestry at each locus. RESULTS: The authors found a region of
      chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI
      (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African
      American participants in the observational, population based Cardiovascular
      Health Study were genotyped at rs9665943 to test the reproducibility of this
      association, and this association was also statistically significant (odds ratio
      (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to
      2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in
      both populations, and was also found to be significantly associated with low AAI
      in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to
      2.76). CONCLUSION: This study identifies a novel region of chromosome 11
      representing an area with a potential candidate gene associated with PAD in
      African Americans.

PMID- 19586930
TI  - Physicochemical property changes of amino acid residues that accompany missense
      mutations in SCN1A affect epilepsy phenotype severity.
AB  - BACKGROUND: Several different missense mutations in the voltage-gated sodium
      channel subunit gene SCN1A have been identified in epileptic patients with benign
      phenotype and patients with severe phenotype. However, the reason why similar
      missense mutations in SCN1A result in different phenotypes has not yet been fully
      clarified. OBJECTIVE: To clarify the phenotype-genotype relationship in SCN1A, a
      meta-analysis was performed to quantitatively determine the effect of amino acid
      substitutions in SCN1A on epilepsy severity phenotype using physicochemical
      property indices of the amino acid, and to discuss in the context of the
      molecular evolution of the proteins. METHODS: PubMed was searched for articles
      and information was extracted on localisation and types of SCN1A missense
      mutations in patients with benign and severe epileptic syndromes; detailed
      information was also extracted. RESULTS: Meta-analysis quantitatively revealed
      that the physicochemical properties of several amino acids significantly affected
      epilepsy phenotype severity. It showed that missense mutations that decreased
      protein hydrophobicity were significantly associated with severe epilepsy
      phenotypes. It also showed that the phenotype severity of SCN1A missense
      mutations in the transmembrane domains of SCN1A (128/155; 82.6%) could be
      predicted with high sensitivity and positive predictive values using the
      physicochemical property changes, indicating the possibility of phenotype
      prediction for entirely new missense mutations using analytical methods.
      CONCLUSIONS: The results show that changes in the physicochemical properties of
      amino acids affected both the phenotype and clinical symptoms of patients with
      SCN1A missense mutations. This meta-analysis study provides new insights into
      SCN1A gene functions and a new strategy for genetic diagnosis, genetic
      counselling and epilepsy treatment.

PMID- 19586931
TI  - Residual torticollis in patients after strabismus surgery for congenital superior
      oblique palsy.
AB  - AIM: To study postoperative residual vertical deviation and abnormal head posture
      (AHP) after surgical treatment for congenital superior oblique palsy (SOP).
      METHOD: Children with both SOP and AHP who underwent extraocular muscle surgery
      for correction of AHP were recruited. The patients received complete ophthalmic
      and orthopaedic examinations. Residual AHP was classified according to severity
      of face turn, head tilt and chin elevation. RESULTS: Thirty-two children with
      mean age at operation of 82.6 months were recruited, with mean follow-up of 37.9
      months. Of these children, 65.6% had a postoperative vertical deviation of less
      than three prism dioptres. In addition, 34.4% patients had resolved (0 degrees ),
      34.4% had mild (1 degrees -10 degrees ), and 31.3% had significant residual
      torticollis (>10 degrees ). Of the patients with significant residual
      torticollis, 33.3% had ocular causes. The mean age at operation for the patients
      with residual torticollis (95.9 months) was older than those without torticollis
      (79.9 months) (p = 0.018). Residual torticollis was found to be related to
      sternocleidomastoid muscle tightness (p = 0.013). CONCLUSION: The success rate
      for eliminating significant AHP after strabismus surgery for patients with
      congenital SOP was 68.8%. Early surgery was associated with a better outcome.
      Association was also found between sternocleidomastoid tightness and AHP. A
      multidisciplinary approach is recommended in the management of torticollis as
      ophthalmic and orthopaedic comorbidities can coexist.

PMID- 19586932
TI  - Dissecting protein-induced DNA looping dynamics in real time.
AB  - Many proteins that interact with DNA perform or enhance their specific functions
      by binding simultaneously to multiple target sites, thereby inducing a loop in
      the DNA. The dynamics and energies involved in this loop formation influence the
      reaction mechanism. Tethered particle motion has proven a powerful technique to
      study in real time protein-induced DNA looping dynamics while minimally
      perturbing the DNA-protein interactions. In addition, it permits many single
      molecule experiments to be performed in parallel. Using as a model system the
      tetrameric Type II restriction enzyme SfiI, that binds two copies of its
      recognition site, we show here that we can determine the DNA-protein association
      and dissociation steps as well as the actual process of protein-induced loop
      capture and release on a single DNA molecule. The result of these experiments is
      a quantitative reaction scheme for DNA looping by SfiI that is rigorously
      compared to detailed biochemical studies of SfiI looping dynamics. We also
      present novel methods for data analysis and compare and discuss these with
      existing methods. The general applicability of the introduced techniques will
      further enhance tethered particle motion as a tool to follow DNA-protein dynamics
      in real time.

PMID- 19586934
TI  - Chemical synthesis, DNA incorporation and biological study of a new
      photocleavable 2'-deoxyadenosine mimic.
AB  - The phototriggered cleavage of chemical bonds has found numerous applications in
      biology, particularly in the field of gene sequencing through photoinduced DNA
      strand scission. However, only a small number of modified nucleosides that are
      able to cleave DNA at selected positions have been reported in the literature.
      Herein, we show that a new photoactivable deoxyadenosine analogue, 3-nitro-3
      deaza-2'-deoxyadenosine (d(3-NiA)), was able to induce DNA backbone breakage upon
      irradiation (lambda > 320 nm). The d(3-NiA) nucleoside was chemically
      incorporated at desired positions into 40-mer oligonucleotides as a
      phosphoramidite monomer and subsequent hybridization studies confirmed that the
      resulting modified duplexes display a behaviour that is close to that of the
      related natural sequence. Enzymatic action of the Klenow fragment exonuclease
      free revealed the preferential incorporation of dAMP opposite the 3-NiA base. On
      the other hand, incorporation of the analogous 3-NiA triphosphate to a primer
      revealed high enzyme efficiency and selectivity for insertion opposite thymine.
      Furthermore, only the enzymatically synthesized base pair 3-NiA:T was a substrate
      for further extension by the enzyme. All the hybridization and enzymatic data
      indicate that this new photoactivable 3-NiA triphosphate can be considered as a
      photochemically cleavable dATP analogue.

PMID- 19586933
TI  - In the absence of writhe, DNA relieves torsional stress with localized, sequence
      dependent structural failure to preserve B-form.
AB  - To understand how underwinding and overwinding the DNA helix affects its
      structure, we simulated 19 independent DNA systems with fixed degrees of twist
      using molecular dynamics in a system that does not allow writhe. Underwinding DNA
      induced spontaneous, sequence-dependent base flipping and local denaturation,
      while overwinding DNA induced the formation of Pauling-like DNA (P-DNA). The
      winding resulted in a bimodal state simultaneously including local structural
      failure and B-form DNA for both underwinding and extreme overwinding. Our
      simulations suggest that base flipping and local denaturation may provide a
      landscape influencing protein recognition of DNA sequence to affect, for
      examples, replication, transcription and recombination. Additionally, our
      findings help explain results from single-molecule experiments and demonstrate
      that elastic rod models are strictly valid on average only for unstressed or
      overwound DNA up to P-DNA formation. Finally, our data support a model in which
      base flipping can result from torsional stress.

PMID- 19586935
TI  - Hybridization modeling of oligonucleotide SNP arrays for accurate DNA copy number
      estimation.
AB  - Affymetrix SNP arrays have been widely used for single-nucleotide polymorphism
      (SNP) genotype calling and DNA copy number variation inference. Although numerous
      methods have achieved high accuracy in these fields, most studies have paid
      little attention to the modeling of hybridization of probes to off-target allele
      sequences, which can affect the accuracy greatly. In this study, we address this
      issue and demonstrate that hybridization with mismatch nucleotides (HWMMN) occurs
      in all SNP probe-sets and has a critical effect on the estimation of allelic
      concentrations (ACs). We study sequence binding through binding free energy and
      then binding affinity, and develop a probe intensity composite representation
      (PICR) model. The PICR model allows the estimation of ACs at a given SNP through
      statistical regression. Furthermore, we demonstrate with cell-line data of known
      true copy numbers that the PICR model can achieve reasonable accuracy in copy
      number estimation at a single SNP locus, by using the ratio of the estimated AC
      of each sample to that of the reference sample, and can reveal subtle genotype
      structure of SNPs at abnormal loci. We also demonstrate with HapMap data that the
      PICR model yields accurate SNP genotype calls consistently across samples,
      laboratories and even across array platforms.

PMID- 19586936
TI  - Frequency and clinical relevance of DNA microsatellite alterations of the
      CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell
      lymphoblastic lymphoma and T-cell lymphoblastic leukemia.
AB  - Although deletions of cell cycle regulatory gene loci have long been reported in
      various malignancies, little is known regarding their relevance in pediatric T
      cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (TALL). The
      current study focused on loss of heterozygosity (LOH) analyses of the CDKN2A/B
      (chromosome 9p), ATM (chromosome 11q) and p53 (chromosome 17p) gene loci.
      Frequencies of LOH were compared in 113 pediatric T-LBL and 125 T-ALL who were
      treated uniformly according to ALL-BFM strategies. Furthermore, LOH findings were
      correlated with clinical characteristics and tested for their prognostic
      relevance. LOH at 9p was detected in 47% of T-LBL and 51% of T-ALL, and was
      associated with male gender in both. In T-ALL, LOH at 9p was associated with
      favorable initial treatment response. A tendency for favorable event-free
      survival was observed in LOH 9p positive T-LBL. The frequency of LOH at
      chromosomes 11q and 17p was 5% or less for both diseases.

PMID- 19586937
TI  - Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell
      transplantation for primary treatment of diffuse large B-cell lymphoma with a
      poor prognosis: a phase II multicenter study.
AB  - BACKGROUND: We investigated the addition of rituximab to dose-dense and high-dose
      chemotherapy with autologous stem cell transplantation in patients with untreated
      poor-prognosis diffuse large B-cell lymphoma. DESIGN AND METHODS: Ninety-four
      young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at
      intermediate/high or high risk according to the age-adjusted International
      Prognostic Index were enrolled into a phase II trial. The treatment was as
      follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin
      vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone
      cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan
      (BEAM) with autologous stem cell transplantation. RESULTS: The complete response
      and toxic death rates were 82% and 5%, respectively. Failure-free survival and
      overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of
      these patients were retrospectively compared to those of 41 patients with similar
      characteristics enrolled into a previous phase II trial of high-dose chemotherapy
      without rituximab. This historical group was treated with eight weekly infusions
      of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin
      (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation.
      The 4-year failure-free survival rates for the rituximab and historical groups
      were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates
      were 80% and 54%, respectively (p=0.002). A Cox's multivariable model was applied
      to adjust the effect of treatment for unbalanced or important prognostic factors:
      failure and death risks were significantly reduced in the rituximab group
      compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01)
      for failure-free survival and 0.46 (p=0.02) for overall survival. CONCLUSIONS:
      These results suggest that the addition of rituximab to high-dose chemotherapy is
      effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and
      such regimens need to be compared to dose-dense chemoimmunotherapy without
      autologous stem cell transplantation in randomized trials.

PMID- 19586939
TI  - Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic
      anemia.
AB  - Cytokine expression assessed by flow cytometry in 53 acquired aplastic anemia
      patients before and after combined immunosuppression (EBMT WPSAA protocols)
      showed that CD3(+) marrow cells containing TNF-alpha, IFN-gamma and IL4 were
      similar in subjects with disease at onset (DO) and responsive to treatment who
      had more CD3(+)/TNF-alpha(+) and CD 3(+)/IFN-gamma(+) cells than normal controls.
      In vitro block of TNF-alpha and/or IFN-gamma significantly increased BFU-e over
      baseline in 28 patients. In responsive to treatment patients only TNF-alpha block
      significantly incremented colonies over normal controls. Absolute marrow
      CD3(+)/TNF-alpha(+) and CD3(+)/IFN-gamma(+) cells prospectively tested in a group
      of 21 subjects declined significantly more in Responders than in Non Responders
      to immunosuppression at Response Evaluation Time respect to Diagnosis. Both in
      Responders and in Non Responders these cells remained higher than in normal
      controls. This study suggests that immunosuppression does not fully clear excess
      TNF-alpha and IFN-gamma from marrow of patients with good outcome and raises the
      hypothesis that additional cytokine blockade might be useful in immunosuppression
      for acquired aplastic anemia.

PMID- 19586940
TI  - Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the
      dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21.
AB  - The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with
      acute lymphoblastic leukemia. Although it results in loss of material from 9p and
      20q, the molecular targets on both chromosomes have not been fully elucidated.
      From an initial cohort of 58 with acute lymphoblastic leukemia patients with this
      translocation, breakpoint mapping with fluorescence in situ hybridization on 26
      of them revealed breakpoint heterogeneity of both chromosomes. PAX5 has been
      proposed to be the target gene on 9p, while for 20q, FISH analysis implicated the
      involvement of the ASXL1 gene, either by a breakpoint within (n=4) or centromeric
      (deletion, n=12) of the gene. Molecular copy-number counting, long-distance
      inverse PCR and direct sequence analysis identified six dic(9;20) breakpoint
      sequences. In addition to the three previously reported: PAX5-ASXL1, PAX5
      C20ORF112 and PAX5-KIF3B; we identified three new ones in this study: sequences
      3' of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3' of FRG1B and
      LOC1499503. This study provides insight into the breakpoint complexity underlying
      dicentric chromosomal formation in acute lymphoblastic leukemia and highlights
      putative target gene loci.

PMID- 19586938
TI  - How and why minimal residual disease studies are necessary in leukemia: a review
      from WP10 and WP12 of the European LeukaemiaNet.
AB  - Resistance to therapeutic agents is a major factor in the failure of cancer
      treatments. In leukemia, the resistant cells remaining in the bone marrow and/or
      peripheral blood constitute minimal residual disease and are detectable by highly
      sensitive assays when the patient appears to be in complete remission. Early
      detection of the expansion of residual cells permits clinical intervention with
      the aim of reversing the proliferation of resistant leukemic cells. Therefore,
      accurate and precise measurement of minimal residual disease can greatly enhance
      optimization of oncology patients' clinical management. This notion is supported
      by a large body of data among chronic myeloid leukemia patients, but minimal
      residual disease detection and monitoring is increasingly applied to other types
      of leukemia, and is starting to be a factor in decision-making for some
      therapeutic trials in childhood acute lymphoblastic leukemia. Here, from the
      solid ground of minimal residual disease detection in chronic myeloid leukemia,
      the current state of the art and development of molecular techniques in other
      leukemias and the growing field of multiparameter flow cytometry are reviewed in
      two separate parts reporting on the respective advances, advantages and pitfalls
      of these emerging methods.

PMID- 19586941
TI  - Genetic and immune-related factors in the pathogenesis of lymphoproliferative and
      plasma cell malignancies.
AB  - There are data to support a role for genetic and immune-related factors in the
      pathogenesis of lymphomas and plasma cell diseases. In this paper, we review our
      published large population-based studies and other relevant studies in Hodgkin's
      and non-Hodgkin's lymphomas, multiple myeloma, and the precursor condition
      monoclonal gammopathy of undetermined significance. We discuss the overlap in
      risk factors between related malignancies and explore the underlying mechanisms.
      Based on these studies, we provide clinical implications and discuss the
      relevance of these data for patient counseling and clinical follow-up. Finally,
      we suggest future directions for new studies designed to increase our current
      knowledge and to define underlying biological mechanisms of our findings.

PMID- 19586942
TI  - The TIR/BB-loop mimetic AS-1 protects the myocardium from ischaemia/reperfusion
      injury.
AB  - AIMS: Innate immune and inflammatory responses are involved in myocardial
      ischaemia/reperfusion (I/R) injury. The interleukin-1 receptor (IL-1R)-mediated,
      MyD88-dependent nuclear factor kappa B (NF-kappaB) activation pathway plays an
      important role in the induction of innate immunity and inflammation. However, the
      role of the IL-1R-MyD88 pathway in myocardial I/R injury has not been thoroughly
      investigated. We hypothesized that inhibition of the interaction of IL-1R with
      MyD88 will attenuate myocardial ischaemic injury through reducing inflammatory
      responses. METHODS AND RESULTS: Male C57BL/6 mice were subjected to myocardial
      ischaemia (45 min) followed by reperfusion (4 h). In the treatment group, after
      mice were subjected to ischaemia (45 min), the TIR/BB-loop mimetic (AS-1), which
      inhibits the interaction of IL-1R with MyD88, was administered immediately before
      reperfusion. Hearts were harvested and cellular proteins were isolated for
      immunoprecipitation and immunoblotting. AS-1 administration significantly
      decreased infarct size by 32.92% compared with the untreated I/R group. Ejection
      fraction and fractional shortening in AS-1-treated mice were also significantly
      increased by 18.0 and 25.6%, respectively, compared with the untreated I/R group.
      AS-1 administration significantly decreased the I/R-increased interaction between
      IL-1R and MyD88, attenuated the I/R-increased NF-kappaB binding activity, and
      reduced levels of inflammatory cytokines and adhesion molecules in the myocardium
      compared with the untreated I/R group. In addition, AS-1 administration
      significantly decreased myocardial myeloperoxidase activity by 23.6% and
      neutrophil infiltration in the myocardium compared with the untreated I/R group.
      CONCLUSION: The results demonstrated an important role for the IL-1R-mediated
      MyD88-dependent signalling pathway in myocardial I/R injury. The data suggest
      that modulation of the IL-1R/MyD88 interaction could be a strategy for reducing
      myocardial ischaemic injury.

PMID- 19586943
TI  - Vascular endothelial ageing, heartbeat after heartbeat.
AB  - The vascular endothelium starts to age at the first heartbeat. There is no longer
      a need to demonstrate that an increased resting heart rate--above 70 b.p.m.--is
      associated with the onset of cardiovascular events and reduces lifespan in
      humans. Each cardiac cycle imposes a mechanical constraint on the arteries, and
      we would like to propose that this mechanical stress damages the vascular
      endothelium, its dysfunction being the prerequisite for atherogenesis.
      Consequently, reducing heart rate could protect the endothelium and slow the
      onset of atherosclerosis. The potential mechanisms by which reducing heart rate
      could be beneficial to the endothelium are likely a combination of a reduction in
      mechanical stress and tissue fatigue and a prolongation of the period of steady
      laminar flow, and thus sustained shear stress, between each systole. With age,
      irreparable damage accumulates in endothelial cells and leads to senescence,
      which is characterized by a pro-atherogenic phenotype. In the body, the highest
      mechanical stress occurs in the coronary vessels, where blood only flows during
      diastole and even reverses during systole; thus, coronary arteries are the prime
      site of atherosclerosis. All classical risk factors for cardiovascular diseases
      add up, to accelerate atherogenesis, but hypertension, which further raises
      mechanical stress, is likely the most damaging. By inducing flow through the
      arteries, the heart rate determines shear stress and its stability: mechanical
      stress and the associated damage induced by each systole are efficiently
      counteracted by the repair capacities of a healthy endothelium. The maintenance
      of a physiological, low heart rate may be key to prolonging the endothelial
      healthy lifespan and thus, vascular health.

PMID- 19586944
TI  - Odour intensity learning in fruit flies.
AB  - Animals' behaviour towards odours depends on both odour quality and odour
      intensity. While neuronal coding of odour quality is fairly well studied, how
      odour intensity is treated by olfactory systems is less clear. Here we study
      odour intensity processing at the behavioural level, using the fruit fly
      Drosophila melanogaster. We trained flies by pairing a MEDIUM intensity of an
      odour with electric shock, and then, at a following test phase, measured flies'
      conditioned avoidance of either this previously trained MEDIUM intensity or a
      LOWer or a HIGHer intensity. With respect to 3-octanol, n-amylacetate and 4
      methylcyclohexanol, we found that conditioned avoidance is strongest when
      training and test intensities match, speaking for intensity-specific memories.
      With respect to a fourth odour, benzaldehyde, on the other hand, we found no such
      intensity specificity. These results form the basis for further studies of odour
      intensity processing at the behavioural, neuronal and molecular level.

PMID- 19586945
TI  - Sex-biased dispersal patterns depend on the spatial scale in a social rodent.
AB  - Dispersal is a fundamental process in ecology because it influences the dynamics,
      genetic structure and persistence of populations. Furthermore, understanding the
      evolutionary causes of dispersal pattern, particularly when they differ between
      genders, is still a major question in evolutionary ecology. Using a panel of 10
      microsatellite loci, we investigated at different spatial scales the genetic
      structure and the sex-specific dispersal patterns in the common vole Microtus
      arvalis, a small colonial mammal. This study was conducted in an intensive
      agricultural area of western France. Hierarchical F(ST) analyses, relatedness and
      assignment tests suggested (i) that females are strongly kin-clustered within
      colonies; (ii) that dispersal is strongly male-biased at a local scale; and (iii)
      long-distance dispersal is not rare and more balanced between genders. We
      conclude that males migrate continuously from colony to colony to reproduce,
      whereas females may disperse just once and would be mainly involved in new colony
      foundation.

PMID- 19586946
TI  - Climate shaped the worldwide distribution of human mitochondrial DNA sequence
      variation.
AB  - There is an ongoing discussion in the literature on whether human mitochondrial
      DNA (mtDNA) evolves neutrally. There have been previous claims for natural
      selection on human mtDNA based on an excess of non-synonymous mutations and
      higher evolutionary persistence of specific mitochondrial mutations in Arctic
      populations. However, these findings were not supported by the reanalysis of
      larger datasets. Using a geographical framework, we perform the first direct test
      of the relative extent to which climate and past demography have shaped the
      current spatial distribution of mtDNA sequences worldwide. We show that
      populations living in colder environments have lower mitochondrial diversity and
      that the genetic differentiation between pairs of populations correlates with
      difference in temperature. These associations were unique to mtDNA; we could not
      find a similar pattern in any other genetic marker. We were able to identify two
      correlated non-synonymous point mutations in the ND3 and ATP6 genes characterized
      by a clear association with temperature, which appear to be plausible targets of
      natural selection producing the association with climate. The same mutations have
      been previously shown to be associated with variation in mitochondrial pH and
      calcium dynamics. Our results indicate that natural selection mediated by climate
      has contributed to shape the current distribution of mtDNA sequences in humans.

PMID- 19586948
TI  - Express your personality or go along with the group: what determines the
      behaviour of shoaling perch?
AB  - Behavioural syndromes, defined as correlated behaviours in different contexts,
      have been studied across species and taxa including humans as part of a
      personality concept. While most studies have focused on solitary individuals,
      less is known on how shoaling fish compromise between own personality and group
      behaviour. Risk-taking behaviour in 1-year-old perch (Perca fluviatilis) was
      observed to compare individual behaviour when in a group and when alone. An
      experimental design gave the fish the choice between foraging in an open area in
      the presence of a piscivore and hiding in the vegetation. We quantified the
      variation accountable by the effect of individuals being in a group, individuals
      alone and repeated measurements, using hierarchical mixed effects models. Within
      group variances were low, but when individuals were later tested alone,
      individual differences explained most of the variation. Still, the individual
      best linear unbiased predictors (BLUPs) of time spent in the open area, extracted
      from the random effects of the mixed effects model, were positively correlated
      with the corresponding BLUPs when alone. The results indicate that individual
      behavioural traits are to some degree expressed also within groups. Most fish
      showed a shyer behaviour when alone, but bolder individuals changed less between
      treatments than did shyer ones, suggesting a more influential role of bold fish
      in the group.

PMID- 19586947
TI  - Ageing in a variable habitat: environmental stress affects senescence in parasite
      resistance in St Kilda Soay sheep.
AB  - Despite widespread empirical evidence for a general deterioration in the majority
      of traits with advancing age, it is unclear whether the progress of senescence is
      chronologically determined, or whether factors such as environmental conditions
      experienced over the lifespan are more important. We explored the relative
      importance of 'chronological' and 'environmental' measures of age to changes in
      parasite resistance across the lifespan of free-living Soay sheep. Our results
      show that individuals experience an increase in parasite burden, as indicated by
      gastrointestinal helminth faecal egg count (FEC) with chronological age. However,
      chronological age fails to fully explain changes in FEC because a measure of
      environmental age, cumulative environmental stress, predicts an additional
      increase in FEC once chronological age has been accounted for. Additionally, we
      show that in females age-specific changes are dependent upon the environmental
      conditions experienced across individuals' life histories: increases in FEC with
      age were greatest among individuals that had experienced the highest degree of
      stress. Our results illustrate that chronological age alone may not always
      correspond to biological age, particularly in variable environments. In these
      circumstances, measures of age that capture the cumulative stresses experienced
      by an individual may be useful for understanding the process of senescence.

PMID- 19586949
TI  - Influence of sexual selection and feeding functional morphology on
      diversification rate of parrotfishes (Scaridae).
AB  - Scaridae (parrotfishes) is a prominent clade of 96 species that shape coral reef
      communities worldwide through their actions as grazing herbivores.
      Phylogenetically nested within Labridae, the profound ecological impact and high
      species richness of parrotfishes suggest that their diversification and
      ecological success may be linked. Here, we ask whether parrotfish evolution is
      characterized by a significant burst of lineage diversification and whether
      parrotfish diversity is shaped more strongly by sexual selection or modifications
      of the feeding mechanism. We first examined scarid diversification within the
      greater context of labrid diversity. We used a supermatrix approach for 252
      species to propose the most extensive phylogenetic hypothesis of Labridae to
      date, and time-calibrated the phylogeny with fossil and biogeographical data.
      Using divergence date estimates, we find that several parrotfish clades exhibit
      the highest diversification rates among all labrid lineages. Furthermore, we
      pinpoint a rate shift at the shared ancestor of Scarus and Chlorurus, a scarid
      subclade characterized by territorial behaviour and strong sexual dichromatism,
      suggesting that sexual selection was a major factor in parrotfish
      diversification. Modifications of the pharyngeal and oral jaws that happened
      earlier in parrotfish evolution may have contributed to this diversity by
      establishing parrotfishes as uniquely capable reef herbivores.

PMID- 19586950
TI  - How sea lice from salmon farms may cause wild salmonid declines in Europe and
      North America and be a threat to fishes elsewhere.
AB  - Fishes farmed in sea pens may become infested by parasites from wild fishes and
      in turn become point sources for parasites. Sea lice, copepods of the family
      Caligidae, are the best-studied example of this risk. Sea lice are the most
      significant parasitic pathogen in salmon farming in Europe and the Americas, are
      estimated to cost the world industry euro300 million a year and may also be
      pathogenic to wild fishes under natural conditions. Epizootics,
      characteristically dominated by juvenile (copepodite and chalimus) stages, have
      repeatedly occurred on juvenile wild salmonids in areas where farms have sea lice
      infestations, but have not been recorded elsewhere. This paper synthesizes the
      literature, including modelling studies, to provide an understanding of how one
      species, the salmon louse, Lepeophtheirus salmonis, can infest wild salmonids
      from farm sources. Three-dimensional hydrographic models predicted the
      distribution of the planktonic salmon lice larvae best when they accounted for
      wind-driven surface currents and larval behaviour. Caligus species can also cause
      problems on farms and transfer from farms to wild fishes, and this genus is
      cosmopolitan. Sea lice thus threaten finfish farming worldwide, but with the
      possible exception of L. salmonis, their host relationships and transmission
      adaptations are unknown. The increasing evidence that lice from farms can be a
      significant cause of mortality on nearby wild fish populations provides an
      additional challenge to controlling lice on the farms and also raises
      conservation, economic and political issues about how to balance aquaculture and
      fisheries resource management.

PMID- 19586951
TI  - Sperm: seminal fluid interactions and the adjustment of sperm quality in relation
      to female attractiveness.
AB  - An important predictor of male fitness is the fertilizing efficiency of their
      ejaculates. Ejaculates are costly to produce and males are predicted to devote
      greater resources to copulations with reproductively superior females. It is well
      established that males allocate different numbers of sperm to ejaculates.
      However, less is known about how males adjust their sperm quality, which has
      important implications for our understanding of fertilization and the evolution
      of sexual strategies. Here we test in the fowl, Gallus gallus, whether males
      adjust their sperm velocity by differentially allocating seminal fluid to
      copulations with attractive and unattractive females. To disentangle the
      contributions of sperm and seminal fluid to sperm velocity, we separated and
      remixed sperm and seminal fluid from ejaculates allocated to females of different
      attractiveness. We show that dominant males increase the velocity of the sperm
      they invest in more attractive females by allocating larger ejaculates that
      contain seminal fluid that increases sperm velocity. Furthermore, we find weak
      evidence that males also allocate sperm with higher velocity, irrespective of
      seminal fluid, to more attractive females.

PMID- 19586952
TI  - A new Lower Cretaceous bird from China and tooth reduction in early avian
      evolution.
AB  - A new avian genus and species, Zhongjianornis yangi gen. et sp. nov., is reported
      from the Lower Cretaceous lacustrine deposits of the Jiufotang Formation in
      Liaoning, northeast China. The new taxon is characterized by possessing the
      following combination of features: upper and lower jaws toothless, snout pointed,
      humerus with large and robust deltopectoral crest, second phalanx of the major
      manual digit longer than the first phalanx, unguals of the alular and major
      digits of similar length and significantly shorter than the corresponding
      penultimate phalanges, tibiotarsus slender and more than twice the length of the
      tarsometatarsus, and metatarsal IV longer than the other metatarsals.
      Phylogenetic analysis indicates that Zhongjianornis is phylogenetically basal to
      Confuciusornis and the dominant Mesozoic avian groups, Enantiornithes and
      Ornithurae, and therefore provides significant new information regarding the
      diversification of birds in the Early Cretaceous. It also represents the most
      basal bird that completely lacks teeth, suggesting that tooth loss was more
      common than expected in early avian evolution and that the avian beak appeared
      independently in several avian lineages, most probably as a response to selective
      pressure for weight reduction. Finally, the presence of a significantly enlarged
      humeral deltopectoral crest suggests that Zhongjianornis shares with other basal
      birds such as Jeholornis, Sapeornis and Confuciusornis a distinctive mode of
      adaptation for flight contrasting with that seen in more advanced birds, which
      instead possess an elongated sternum and a prominent keel.

PMID- 19586953
TI  - Large crystal growth by thermal control allows combined X-ray and neutron
      crystallographic studies to elucidate the protonation states in Aspergillus
      flavus urate oxidase.
AB  - Urate oxidase (Uox) catalyses the oxidation of urate to allantoin and is used to
      reduce toxic urate accumulation during chemotherapy. X-ray structures of Uox with
      various inhibitors have been determined and yet the detailed catalytic mechanism
      remains unclear. Neutron crystallography can provide complementary information to
      that from X-ray studies and allows direct determination of the protonation states
      of the active-site residues and substrate analogues, provided that large, well
      ordered deuterated crystals can be grown. Here, we describe a method and
      apparatus used to grow large crystals of Uox (Aspergillus flavus) with its
      substrate analogues 8-azaxanthine and 9-methyl urate, and with the natural
      substrate urate, in the presence and absence of cyanide. High-resolution X-ray
      (1.05-1.20 A) and neutron diffraction data (1.9-2.5 A) have been collected for
      the Uox complexes at the European Synchrotron Radiation Facility and the Institut
      Laue-Langevin, respectively. In addition, room temperature X-ray data were also
      collected in preparation for joint X-ray and neutron refinement. Preliminary
      results indicate no major structural differences between crystals grown in H(2)O
      and D(2)O even though the crystallization process is affected. Moreover, initial
      nuclear scattering density maps reveal the proton positions clearly, eventually
      providing important information towards unravelling the mechanism of catalysis.

PMID- 19586955
TI  - Atomic-scale dynamics inside living cells explored by neutron scattering.
AB  - Single-particle neutron spectroscopy has contributed important experimental data
      on molecular dynamics in biological systems. The technique provides information
      on atomic and molecular motions in macromolecules on the picosecond to the
      nanosecond time scale, which are essential to biological function. Here, we
      report on recent neutron measurements performed directly in living cells by using
      isotope labelling to explore the dynamics of specific cellular components. The
      paper proposes an integrated view of results on atomic-scale cell water dynamics,
      internal and global macromolecular motions and solvent isotope effect on
      macromolecular dynamics. The work established the specific usefulness of the
      neutron scattering technique to get insight into biologically relevant dynamical
      features, in particular through comparative measurements. The method developed
      can now be applied to look for dynamical signatures related to cell
      characteristics in many different cell types and organelles.

PMID- 19586954
TI  - Oxidative stress and inflammation response after nanoparticle exposure:
      differences between human lung cell monocultures and an advanced three
      dimensional model of the human epithelial airways.
AB  - Combustion-derived and manufactured nanoparticles (NPs) are known to provoke
      oxidative stress and inflammatory responses in human lung cells; therefore, they
      play an important role during the development of adverse health effects. As the
      lungs are composed of more than 40 different cell types, it is of particular
      interest to perform toxicological studies with co-cultures systems, rather than
      with monocultures of only one cell type, to gain a better understanding of
      complex cellular reactions upon exposure to toxic substances. Monocultures of
      A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte
      derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of
      all three cell types were exposed to combustion-derived NPs (diesel exhaust
      particles) and to manufactured NPs (titanium dioxide and single-walled carbon
      nanotubes). The penetration of particles into cells was analysed by transmission
      electron microscopy. The amount of intracellular reactive oxygen species (ROS),
      the total antioxidant capacity (TAC) and the production of tumour necrosis factor
      (TNF)-alpha and interleukin (IL)-8 were quantified. The results of the
      monocultures were summed with an adjustment for the number of each single cell
      type in the triple cell co-culture. All three particle types were found in all
      cell and culture types. The production of ROS was induced by all particle types
      in all cell cultures except in monocultures of MDDCs. The TAC and the (pro
      )inflammatory reactions were not statistically significantly increased by
      particle exposure in any of the cell cultures. Interestingly, in the triple cell
      co-cultures, the TAC and IL-8 concentrations were lower and the TNF-alpha
      concentrations were higher than the expected values calculated from the
      monocultures. The interplay of different lung cell types seems to substantially
      modulate the oxidative stress and the inflammatory responses after NP exposure.

PMID- 19586956
TI  - Melanocyte pigmentation stiffens murine cardiac tricuspid valve leaflet.
AB  - Pigmentation of murine cardiac tricuspid valve leaflet is associated with
      melanocyte concentration, which affects its stiffness. Owing to its biological
      and viscoelastic nature, estimation of the in situ stiffness measurement becomes
      a challenging task. Therefore, quasi-static and nanodynamic mechanical analysis
      of the leaflets of the mouse tricuspid valve is performed in the current work.
      The mechanical properties along the leaflet vary with the degree of pigmentation.
      Pigmented regions of the valve leaflet that contain melanocytes displayed higher
      storage modulus (7-10 GPa) than non-pigmented areas (2.5-4 GPa). These results
      suggest that the presence of melanocytes affects the viscoelastic properties of
      the mouse atrioventricular valves and are important for their proper functioning
      in the organism.

PMID- 19586957
TI  - Prospective virtual screening with Ultrafast Shape Recognition: the
      identification of novel inhibitors of arylamine N-acetyltransferases.
AB  - There is currently a shortage of chemical molecules that can be used as bioactive
      probes to study molecular targets and potentially as starting points for drug
      discovery. One inexpensive way to address this problem is to use computational
      methods to screen a comprehensive database of small molecules to discover novel
      structures that could lead to alternative and better bioactive probes. Despite
      that pleasing logic the results have been somewhat mixed. Here we describe a
      virtual screening technique based on ligand-receptor shape complementarity,
      Ultrafast Shape Recognition (USR). USR is specifically applied to identify novel
      inhibitors of arylamine N-acetyltransferases by computationally screening almost
      700 million molecular conformers in a time- and resource-efficient manner. A
      small number of the predicted active compounds were purchased and tested
      obtaining a confirmed hit rate of 40 per cent which is an outstanding result for
      a prospective virtual screening.

PMID- 19586958
TI  - Comparison of economical aspects of interscalene brachial plexus blockade and
      general anaesthesia for arthroscopic shoulder surgery.
AB  - BACKGROUND: This study investigated the cost-effectiveness of ultrasonographic
      guided interscalene brachial plexus blockade (ISB) in comparison with general
      anaesthesia (GA) for arthroscopic shoulder surgery. METHODS: Forty patients
      undergoing arthroscopic shoulder surgery received either an ultrasonographic
      guided ISB or GA. ISB was performed outside the operation room (OR) and patients
      were transferred in the OR at the earliest 20 min after block performance. All
      drugs and disposables were recorded to evaluate the costs for both techniques.
      The following anaesthesia-related times were defined: ready for surgical
      preparation (from arrival in the OR until end of anaesthesia induction), OR
      emergence time (from end of dressing until leaving the OR), anaesthesia control
      time (from patient's arrival in the OR until readiness for positioning plus time
      from the end of surgery to patient's discharge from the OR), and post-anaesthesia
      care unit (PACU) time (from patient's arrival in the PACU to the eligibility for
      discharge to normal ward). Personnel costs were excluded from statistical
      analysis. RESULTS: The total costs were [mean (sd)] 33 (9)euro for patients with
      ISB and 41 (7)euro for those who received GA (P<0.01). The anaesthesia-related
      workflow was improved in the ISB group when compared with the GA group [ready for
      surgical preparation 8 (3) vs 13 (5) min, P<0.001; OR emergence time 4 (3) vs 10
      (5), P<0.001; anaesthesia control time 12 (4) vs 23 (6), P<0.001; and PACU time
      45 (17) vs 70 (20), P<0.001]. CONCLUSIONS: Ultrasonographic-guided ISB is a cost
      effective method for arthroscopic shoulder surgery.

PMID- 19586959
TI  - Autologous mesenchymal stem cells produce reverse remodelling in chronic
      ischaemic cardiomyopathy.
AB  - AIMS: The ability of mesenchymal stem cells (MSCs) to heal the chronically
      injured heart remains controversial. Here we tested the hypothesis that
      autologous MSCs can be safely injected into a chronic myocardial infarct scar,
      reduce its size, and improve ventricular function. METHODS AND RESULTS: Female
      adult Gottingen swine (n = 15) underwent left anterior descending coronary artery
      balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone
      marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks
      post-myocardial infarction (MI), animals were randomized to receive surgical
      injection of either phosphate buffered saline (placebo, n = 6), 20 million (low
      dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct
      and border zone. Injections were administered to the beating heart via left
      anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to
      evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV)
      function. There was no difference in mortality, post-injection arrhythmias,
      cardiac enzyme release, or systemic inflammatory markers between groups. Whereas
      MI size remained constant in placebo and exhibited a trend towards reduction in
      low dose, high-dose MSC therapy reduced infarct size from 18.2 +/- 0.9 to 14.4 +/
      1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments
      increased regional contractility and MBF in both infarct and border zones.
      Ectopic tissue formation was not observed with MSCs. CONCLUSION: Together these
      data demonstrate that autologous MSCs can be safely delivered in an adult heart
      failure model, producing substantial structural and functional reverse
      remodelling. These findings demonstrate the safety and efficacy of autologous MSC
      therapy and support clinical trials of MSC therapy in patients with chronic
      ischaemic cardiomyopathy.

PMID- 19586961
TI  - Idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia
      accompanied with cutaneous involvement and renal dysfunction.
AB  - Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal
      hypergammaglobulinemia has been proposed as a new disease entity resembling the
      plasma cell type of multicentric Castleman's disease. Here, we report a case of
      IPL accompanied by renal failure and skin involvement. A 35-year-old man was
      admitted for advanced renal failure, anemia, systemic lymphadenopathy and skin
      rashes. Laboratory examinations indicated polyclonal hypergammaglobulinemia and
      elevated serum interleukin-6 (IL-6). Biopsy of a cervical lymph node revealed
      follicular hyperplasia with normal germinal centers, sheets of polyclonal
      proliferating plasma cells and the absence of marked proliferation of blood
      vessels in the interfollicular area. Lesions of the kidney and skin also had
      pathological characteristics of IPL. Following a diagnosis of IPL, corticosteroid
      therapy successfully improved the anemia and hypergammaglobulinemia, and serum IL
      6 levels decreased to a normal range. This case may give suggestions about
      diagnosing and preventing the progression of complications from this disease
      entity.

PMID- 19586960
TI  - Reperfusion before percutaneous coronary intervention in ST-elevation myocardial
      infarction patients is associated with lower N-terminal pro-brain natriuretic
      peptide levels during follow-up, irrespective of pre-treatment with full-dose
      fibrinolysis.
AB  - AIMS: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict
      outcomes in ST-elevation myocardial infarction patients treated with fibrinolysis
      or primary percutaneous coronary intervention (PCI). However, its role in
      facilitated PCI has not yet been assessed; it may be a tool to evaluate the lower
      event rates with primary PCI in ASSENT-4. METHODS AND RESULTS: In ASSENT-4, 1667
      patients were randomized to tenecteplase (TNK) followed by PCI or primary PCI
      alone. Baseline, discharge/Day 7, and 90-day NT-proBNP levels were available for
      1008, 971, and 813 patients. Increasing quartiles of baseline NT-proBNP levels
      were associated with a higher risk of the combined endpoint of death, heart
      failure, and shock at 90 days and 1-year mortality (P < 0.001). Events were more
      common with TNK + PCI, regardless of baseline NT-proBNP quartile. When analysing
      baseline NT-proBNP as a continuous variable, no treatment interaction was
      observed for the primary endpoint (P = 0.17) or 1-year mortality (P = 0.08).
      Overall, NT-proBNP levels at Day 7 or 90 were not different between the two
      treatments. In patients with TIMI 2-3 flow before PCI, NT-proBNP at Day 90 was
      lower in PCI-only patients (P = 0.01), although no interaction was observed (P =
      0.14). In TNK-pre-treated patients without reperfusion (TIMI 0-1) after PCI, NT
      proBNP levels at Day 7 or 90 were not significantly higher than in PCI patients.
      CONCLUSION: Baseline NT-proBNP predicts outcome at 90 days and 1 year in patients
      undergoing PCI with or without facilitation with TNK. A higher rate of
      reperfusion in lytic-pre-treated patients did not result in lower NT-proBNP
      during follow-up. Thus, baseline and subsequent NT-proBNP levels do not explain
      the lower mortality rate with PCI alone seen in this trial.

PMID- 19586962
TI  - Is there a role of the histologic subtypes of papillary renal cell carcinoma as a
      prognostic factor?
AB  - OBJECTIVE: The aim of this study was to compare type 1 and type 2 papillary renal
      cell carcinoma (RCC) for validating this subclassification as a prognostic
      factor. METHODS: A total of 70 patients with chromophobe RCC were included in the
      analysis. Patients with papillary RCC were categorized into type 1 (n = 33) and
      type 2 (n = 37). RESULTS: The median progression-free survival was 31.0 months
      for the type 1 group and 12.0 months for the type 2 group (P = 0.001). The median
      cancer-specific survival was 41.1 months for the type 1 group and 24.0 months for
      the type 2 group (P = 0.097). Multivariate Cox proportional hazards model for
      patients with papillary RCC showed that no variables including histologic
      subtyping were independent predictors of progression-free and cancer-specific
      survival. CONCLUSIONS: In the present study, the type of papillary RCC does not
      reach independent prognostic significance.

PMID- 19586963
TI  - Evidence of an evolutionary precursor to human language affixation in a non-human
      primate.
AB  - Human language, and grammatical competence in particular, relies on a set of
      computational operations that, in its entirety, is not observed in other animals.
      Such uniqueness leaves open the possibility that components of our linguistic
      competence are shared with other animals, having evolved for non-linguistic
      functions. Here, we explore this problem from a comparative perspective, asking
      whether cotton-top tamarin monkeys (Saguinus oedipus) can spontaneously (no
      training) acquire an affixation rule that shares important properties with our
      inflectional morphology (e.g. the rule that adds -ed to create the past tense, as
      in the transformation of walk into walk-ed). Using playback experiments, we show
      that tamarins discriminate between bisyllabic items that start with a specific
      'prefix' syllable and those that end with the same syllable as a 'suffix'. These
      results suggest that some of the computational mechanisms subserving affixation
      in a diversity of languages are shared with other animals, relying on basic
      perceptual or memory primitives that evolved for non-linguistic functions.

PMID- 19586964
TI  - Herbivore release through cascading risk effects.
AB  - Predators influence prey through consumption, and through trait-mediated effects
      such as emigration in response to predation risk (risk effects). We studied top
      down effects of (sub-) adult wolf spiders (Lycosidae) on arthropods in a meadow.
      We compared risk effects with the overall top-down effect (including consumption)
      by gluing the chelicers of wolf spiders to prevent them from killing the prey. In
      a field experiment, we created three treatments that included either: (i) intact
      ('predation') wolf spiders; (ii) wolf spiders with glued chelicers ('risk
      spiders'); or (iii) no (sub-) adult wolf spiders. Young wolf spiders were reduced
      by their (sub-) adult congeners. Densities of sheetweb spiders (Linyphiidae), a
      known intraguild prey of wolf spiders, were equally reduced by the presence of
      risk and predation wolf spiders. Plant- and leafhoppers (Auchenorrhyncha) showed
      the inverse pattern of higher densities in the presence of both risk and
      predation wolf spiders. We conclude that (sub-) adult wolf spiders acted as top
      predators, which reduced densities of intermediate predators and thereby enhanced
      herbivores. Complementary to earlier studies that found trait-mediated herbivore
      suppression, our results demonstrate that herbivores can be enhanced through
      cascading risk effects by top predators.

PMID- 19586965
TI  - FORDISC and the determination of ancestry from cranial measurements.
AB  - Determining the ancestry of unidentified human remains is a major task for
      bioarchaeologists and forensic anthropologists. Here, we report an assessment of
      the computer program that has become the main tool for accomplishing this task.
      Called Fordisc, the program determines ancestry through discriminant function
      analysis of cranial measurements. We evaluated the utility of Fordisc with 200
      specimens of known ancestry. We ran the analyses with and without the test
      specimen's source population included in the program's reference sample, and with
      and without specifying the sex of the test specimen. We also controlled for the
      possibility that the number of variables employed affects the program's ability
      to attribute ancestry. The results of the analyses suggest that Fordisc's utility
      in research and medico-legal contexts is limited. Fordisc will only return a
      correct ancestry attribution when an unidentified specimen is more or less
      complete, and belongs to one of the populations represented in the program's
      reference samples. Even then Fordisc can be expected to classify no more than 1
      per cent of specimens with confidence.

PMID- 19586966
TI  - Sex-ratio biasing towards daughters among lower-ranking co-wives in Rwanda.
AB  - There is considerable debate as to whether human females bias the sex ratio of
      their offspring as a function of their own condition. We apply the Trivers
      Willard prediction-that mothers in poor condition will overproduce daughters-to a
      novel measure of condition, namely wife rank within a polygynous marriage. Using
      a large-scale sample of over 95 000 Rwandan mothers, we show that lower-ranking
      polygynous wives do indeed have significantly more daughters than higher-ranking
      polygynous wives and monogamously married women. This effect remains when
      controlling for potential confounds such as maternal age. We discuss these
      results in reference to previous work on sex-ratio adjustment in humans.

PMID- 19586967
TI  - Divergence time of the two regional medaka populations in Japan as a new time
      scale for comparative genomics of vertebrates.
AB  - The southern and northern Japanese populations of the medaka fish provide useful
      tools to gain insights into the comparative genomics and speciation of
      vertebrates, because they can breed to produce healthy and fertile offspring
      despite their highly divergent genetic backgrounds compared with those of human
      chimpanzee. Comparative genomics analysis has suggested that such large genetic
      differences between the two populations are caused by higher molecular
      evolutionary rates among the medakas than those of the hominids. The argument,
      however, was based on the assumption that the two Japanese populations diverged
      approximately at the same time (4.0-4.7 Myr ago) as the human-chimpanzee lineage
      (5.0-6.0 Myr ago). This can be misleading, because the divergence time of the two
      populations was calculated based on estimated, extremely higher molecular
      evolutionary rates of other fishes with an implicit assumption of a global
      molecular clock. Here we show that our estimate, based on a Bayesian relaxed
      molecular-clock analysis of whole mitogenome sequences from 72 ray-finned fishes
      (including 14 medakas), is about four times older than that of the previous study
      (18 Myr). This remarkably older estimate can be reconciled with the vicariant
      events of the Japanese archipelago, and the resulting rates of molecular
      evolution are almost identical between the medaka and hominid lineages. Our
      results further highlight the fact that reproductive isolation may not evolve
      despite a long period of geographical isolation.

PMID- 19586968
TI  - BTS guidelines for home oxygen in children.

PMID- 19586969
TI  - Haemodialysis-induced transient CD16+ monocytopenia and cardiovascular outcome.
AB  - BACKGROUND: Haemodialysis with bioincompatible membranes led to transient
      leukocyte activation and intra-dialytic leukopenia due to endothelial adherence.
      After the introduction of biocompatible membranes, only CD16(+) (i.e.
      CD14(++)CD16(+) and CD14((+))CD16(+)) monocytes showed an impressive transient
      intra-dialytic decrease. Presently, it is unclear whether this CD16(+) monocyte
      drop is detrimental. We investigated whether a prominent intra-dialytic decrease
      of CD16(+) monocytes predicts future cardiovascular (CV) events. METHODS: We
      measured leukocyte and monocyte subpopulations in 70 patients before and 10 min
      after haemodialysis initiation. Patients were stratified by their intra-dialytic
      CD14(++)CD16(+) monocyte drop (pre-defined major drop: decline of cell counts at
      10 min to <50% of pre-dialytic values; pre-defined minor drop: decline to values
      >50% of pre-dialytic counts). Patients were followed up for 42 +/- 2 months;
      endpoints were CV events and death. RESULTS: Patients with a minor
      CD14(++)CD16(+) monocyte drop had more CV events than patients with a major drop.
      In multivariate analysis, a minor CD14(++)CD16(+) monocyte drop was the strongest
      independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192
      4.854)]. CONCLUSIONS: These data refute the assumption that a prominent intra
      dialytic decrease of CD14(++)CD16(+) monocytes is detrimental. Instead, a minor
      cell drop could mirror CD14(++)CD16(+) monocyte dysfunction, with inadequate
      migratory reaction towards an immunologic stimulus posed by membrane and tubing
      contact.

PMID- 19586970
TI  - Incidence of Merkel cell carcinoma in renal transplant recipients.
AB  - BACKGROUND: The risk factors for Merkel cell carcinoma (MCC), a rare type of skin
      cancer, are poorly understood. Some evidence suggests that MCC is more common in
      individuals with abnormal immune function resulting from viral infection,
      autoimmune disease or organ trans- plantation. METHODS: The national Renal
      Transplant Registry and the Finnish Cancer Registry data were searched for
      recipients of a renal transplant who were diagnosed with MCC. The MCC diagnoses
      were confirmed using immunohistochemistry. RESULTS: Three cases of MCC were
      detected among 4200 individuals who underwent renal transplantation from 1967 to
      2005 [expected number 0.05, standardized incidence ratio (SIR) 66, 95% CI 14-194,
      P <0.001]. The latency period between the transplant and detection of MCC ranged
      from 6 to 19 years. In all three cases, the cause of transplantation was an
      autoimmune disease. All three died from aggressive MCC with a survival time
      ranging from 0.5 to 2.1 years. CONCLUSIONS: The results indicate that the risk of
      MCC is greatly increased among subjects who have undergone renal transplantation.
      The course of the disease appears aggressive in this patient population. The
      physicians who treat recipients of a kidney transplant should be aware of the
      substantially increased risk of MCC.

PMID- 19586971
TI  - Home blood pressure monitoring in blood pressure control among haemodialysis
      patients: an open randomized clinical trial.
AB  - BACKGROUND: It is not known if the adjustment of antihypertensive therapy based
      on home blood pressure monitoring (HBPM) can improve blood pressure (BP) control
      among haemodialysis patients. METHODS: This is an open randomized clinical trial.
      Hypertensive patients on haemodialysis were randomized to have the
      antihypertensive therapy adjusted based on predialysis BP measurements or HBPM.
      Before and after 6 months of follow-up, patients were submitted to ambulatory
      blood pressure monitoring (ABPM) for 24 h, HBPM during 1 week and echocardiogram.
      RESULTS: A total of 34 and 31 patients completed the study in the HBPM and
      predialysis BP groups, respectively. At the end of study, the systolic (SBP) and
      diastolic (DBP) blood pressure during the interdialytic period measured by ABPM
      were significantly lower in the HBPM group in relation to the predialysis BP
      group (mean 24-h BP: 135 +/- 12 mmHg/76 +/- 7 mmHg versus 147 +/- 15 mmHg/79 +/-
      8 mmHg; P < 0.05). In the HBPM analysis, the HBPM group showed a significant
      reduction only in SBP compared to the predialysis BP group (weekly mean: 144 +/-
      21 mmHg versus 154 +/- 22 mmHg; P < 0.05). There were no differences between the
      HBPM and predialysis BP groups in relation to the left ventricular mass index at
      the end of the study (108 +/- 35 g/m(2) versus 110 +/- 33 g/m(2); P > 0.05).
      CONCLUSIONS: Decision making based on HBPM among haemodialysis patients has led
      to a better BP control during the interdialytic period in comparison with
      predialysis BP measurements. HBPM may be a useful adjuvant instrument for blood
      pressure control among haemodialysis patients.

PMID- 19586972
TI  - A 2 year old with fever and cough.

PMID- 19586973
TI  - A maths student with psychiatric symptoms.

PMID- 19586977
TI  - Vegetarian diets.

PMID- 19586976
TI  - Repeat falls and the recovery of social participation in the year post-hip
      fracture.
AB  - BACKGROUND: although the majority of hip fractures are the result of a fall,
      whether repeated falls in the year post-fracture adversely influence recovery of
      social participation is not known. DESIGN: analysis of data from a longitudinal
      cohort study. SUBJECTS: community-dwelling women aged > or = 65 years, admitted
      to one of two hospitals in Baltimore with a new, non-pathological fracture of the
      proximal femur between 1992 and 1995. METHODS: information on falls was collected
      from a falls diary. At the baseline, 6- and 12-month evaluations, subjects were
      asked about the number of times in the 2 weeks prior to the evaluation they had
      participated in 10 categories of social activities. We examined the association
      of repeated falls with social participation using generalized estimating
      equations. The effect of physical and psychological functions was examined by
      including measures of lower extremity functional performance and depressive
      symptoms into the model. RESULTS: the analyses included 196 women, mean age =
      80.2 years. Eighty-one subjects fell. The subjects with >1 fall between
      evaluations participated in a mean (95% CI) of 3.5 (0.12, 6.9) and 4.3 (0.9, 7.7)
      fewer social activities at 6 and 12 months post-fracture, respectively, compared
      to those who did not fall (P = 0.0003). These results were attenuated by
      adjustment for depressive symptoms, but not by lower extremity functional
      performance. CONCLUSIONS: in the year post-fracture, repeated falls in women were
      associated with decreased social participation independent of lower extremity
      function. Depressive symptoms in repeated fallers may partly explain this
      association.

PMID- 19586980
TI  - German agency suspects that insulin analogue glargine increases risk of cancer.

PMID- 19586983
TI  - The role of specialists in managing the health of populations with chronic
      illness: the example of chronic kidney disease.
AB  - PROBLEM: Specialty care has been used to manage individual patients at the
      discretion of generalists but not to drive improvements at the population level.
      DESIGN: Observational longitudinal study. SETTING: Kaiser Permanente Hawaii, with
      more than 10,000 members with documented chronic kidney disease. KEY MEASURES FOR
      IMPROVEMENT: Rate of late referrals to nephrology care, defined as occurring
      within four months of end stage renal disease and the proportions of patients
      starting haemodialysis with a mature arteriovenous fistula and starting dialysis
      in the outpatient setting. STRATEGIES FOR CHANGE: Risk stratification of the
      entire population and unsolicited consultations provided by nephrologists to
      generalists, based on patients' risk level, enabled by an electronic population
      management database. EFFECTS OF CHANGE: Between 2004 and 2008, the proportion of
      referrals occurring within four months of onset of end stage renal disease
      dropped from 37 of 116 (32%) to 10 of 84 (12%), P=0.001. The proportion of
      patients starting haemodialysis with a mature arteriovenous fistula increased
      from 19 of 108 (18%) to 27 of 76 (36%), P=0.006. The proportion of patients who
      started haemodialysis as outpatients increased from 39 of 113 (35%) to 47 of 84
      (56%), P=0.003. LESSONS LEARNT: Turning the traditional referral system on its
      head by providing unsolicited, risk driven nephrology consultations is an
      effective strategy for increasing the quality of medical management of patients
      with chronic kidney disease in the primary care setting and improving the cost
      effective use of nephrology services. This approach may be broadly applicable to
      other specialty areas.

PMID- 19586984
TI  - Aspirin for primary prevention. Consensus is urgently required.

PMID- 19586985
TI  - A/H1N1 flu. Policy on antiviral drugs needs to be revised ...

PMID- 19586986
TI  - A/H1N1 flu. Call for flu research under way.

PMID- 19586987
TI  - NICE on back pain. A misreading of the evidence?

PMID- 19586988
TI  - NICE on back pain. The real issues.

PMID- 19586989
TI  - NICE on back pain. Guideline is misleading.

PMID- 19586990
TI  - A/H1N1 flu ... as does policy on antibiotics.

PMID- 19586994
TI  - Catatonia is not schizophrenia: Kraepelin's error and the need to recognize
      catatonia as an independent syndrome in medical nomenclature.
AB  - Catatonia is a motor dysregulation syndrome described by Karl Kahlbaum in 1874.
      He understood catatonia as a disease of its own. Others quickly recognized it
      among diverse disorders, but Emil Kraepelin made it a linchpin of his concept of
      dementia praecox. Eugen Bleuler endorsed this singular association. During the
      20th century, catatonia has been considered a type of schizophrenia. In the
      1970s, American authors identified catatonia in patients with mania and
      depression, as a toxic response, and in general medical and neurologic illnesses.
      It was only occasionally found in patients with schizophrenia. When looked for,
      catatonia is found in 10% or more of acute psychiatric admissions. It is readily
      diagnosable, verifiable by a lorazepam challenge test, and rapidly treatable.
      Even in its most lethal forms, it responds to high doses of lorazepam or to
      electroconvulsive therapy. These treatments are not accepted for patients with
      schizophrenia. Prompt recognition and treatment saves lives. It is time to place
      catatonia into its own home in the psychiatric classification.

PMID- 19586995
TI  - Interleukin (IL)-10 attenuates lipopolysaccharide-induced IL-6 production via
      inhibition of IkappaB-zeta activity by Bcl-3.
AB  - The inhibitory effect of interleukin-10 (IL-10), an anti-inflammatory cytokine,
      on lipopolysaccharide (LPS)-induced IL-6 production was characterized by
      simultaneous stimulation of RAW 264.7 cells with LPS and IL-10. The presence of
      IL-10 significantly inhibited LPS-induced IL-6 production at a transcriptional
      level. The expression of IkappaB-zeta, which promotes IL-6 production, was
      induced in response to LPS and it was definitely suppressed in the presence of IL
      10. Further, IL-10 inhibited LPS-induced NF-kappaB activation. A pharmacological
      inhibitor of NF-kappaB prevented LPS-induced IkappaB-zeta expression, suggesting
      that IL-10 might inhibit LPS-induced IkappaB-zeta expression via the inactivation
      of NF-kappaB. In LPS- and IL-10-stimulated cells, the expression of Bcl-3 that
      inhibits NF-kappaB activation was significantly augmented. Introduction of Bcl-3
      siRNA abolished IL-10-mediated IkappaB-zeta inhibition. In the presence of Bcl-3,
      siRNA IL-10 failed to inhibit LPS-induced IL-6 production. Therefore, it was
      suggested that Bcl-3 induced by IL-10 might reduce LPS-induced IkappaB-zeta
      activity via inactivation of NF-kappaB and that reduced IkappaB-zeta activity
      failed to promote LPS-induced IL-6 production.

PMID- 19586996
TI  - TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and
      resolution of otitis media.
AB  - Otitis media is the most prevalent childhood disease in developed countries. The
      involvement of Toll-like receptors (TLRs) in otitis media pathophysiology has
      been implicated by studies in cell lines and association studies of TLR gene
      polymorphisms. However, precise functions of TLRs in the etiology of otitis media
      in vivo have not been examined. We investigated the inflammatory response to
      nontypeable Haemophilus influenzae using a model of otitis media in wild-type,
      TLR2(- /-) and TLR4(-/ -) mice by gene microarray, qPCR, immunohistochemistry,
      Western blot analysis and histopathology. Toll-like receptor-2(- /-) and TLR4(- /
      ) mice exhibited a more profound, persistent inflammation with impaired bacterial
      clearance compared to controls. While wild-type mice induced tumor necrosis
      factor-a (TNF) after non-typeable H. influenzae challenge, TLR2(-/-) and TLR4(-/
      ) mice lack TNF induction in the early phase of otitis media. Moreover, lack of
      TLR2 resulted in a late increase in IL-10 expression and prolonged failure to
      clear bacteria. Toll-like receptor-4(-/- ) mice showed impaired early bacterial
      clearance and loss of TLR2 induction in early otitis media. Our results
      demonstrate that both TLR2 and TLR4 signalling are critical to the regulation of
      infection in non-typeable H. influenzae-induced otitis media. Toll-like receptor
      4 signalling appears to induce TLR2 expression, and TLR2 activation is critical
      for bacterial clearance and timely resolution of otitis media.

PMID- 19586997
TI  - Detection and quantification of five major periodontal pathogens by single copy
      gene-based real-time PCR.
AB  - Periodontitis is a common chronic multibacterial infection in the tooth
      supporting tissues. It has been shown that periodontitis patients carry higher
      number of disease-associated bacteria than healthy ones. The aim of this study
      was to generate a novel, single copy gene-based quantitative real-time PCR (qPCR)
      assay for five major periodontal pathogens - Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema
      denticola, and Tannerella forsythia. The primer/probe sets were designed for
      conservative lipopolysaccharide-coding gene regions. They proved to be sensitive
      and able to detect strains representing different serotypes of the target
      bacteria. The specificity of designed primers was tested using 49 selected
      bacterial species and no false positive or negative results were observed. We
      validated the assay with a case-control population, including 165 saliva samples,
      and proved the diagnostic accuracy by Receiver Operating Characteristic (ROC)
      curves. All quantified pathogens alone were able to distinguish significantly
      between the subjects with and without periodontitis, and provided areas under the
      ROC curve larger than 0.5. The total pathogen burden comprising all five species
      associated with periodontitis with an area of 0.821 (95% CI, 0.758-0.885,
      P50.001). Our prominently sensitive and specific assay may have major importance
      in the diagnosis, prevention, and treatment of periodontitis.

PMID- 19586999
TI  - Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine
      receptor in LPS-induced neuro-inflammation.
AB  - This study investigated the influence of the cholinergic system on neuro
      inflammation using nicotinic and muscarinic receptor agonists and antagonists.
      Intracerebroventricular (ICV) injection of lipopolysaccharide (LPS, 50 microg)
      was used to induce neuro-inflammation in rats and estimations of pro-inflammatory
      cytokines, alpha7 nicotinic acetylcholine receptor (nAChR) mRNA expression were
      done in striatum, cerebral cortex, hippocampus and hypothalamus at 24 h after LPS
      injection. Nicotine (0.2, 0.4 and 0.8 mg/kg, i.p.) or oxotremorine (0.2, 0.4 and
      0.8 mg/kg, i.p.) were administered 2 h prior to sacrifice. We found that only
      nicotine was able to block the proinflammatory cytokines induced by LPS whereas,
      oxotremorine was found ineffective. Methyllycaconitine (MLA; 1.25, 2.5 and 5
      mg/kg, i.p.), an alpha7 nAChR antagonist or dihydro-beta-erythroidine (DHbetaE;
      1.25, 2.5 and 5 mg/kg, i.p.), an alpha4beta2 nAChR antagonist, was given 20 min
      prior to nicotine in LPS-treated rats. Methyllycaconitine antagonized the anti
      inflammatory effect of nicotine whereas DHbetaE showed no effect demonstrating
      that alpha7 nAChR is responsible for attenuation of LPS-induced pro-inflammatory
      cytokines. This study suggests that the inhibitory role of the central
      cholinergic system on neuro-inflammation is mediated via alpha7 nicotinic
      acetylcholine receptor and muscarinic receptors are not involved.

PMID- 19586998
TI  - The potential role of T-cells and their interaction with antigen-presenting cells
      in mediating immunosuppression following trauma-hemorrhage.
AB  - OBJECTIVE: Trauma-hemorrhage results in depressed immune responses of antigen
      presenting cells (APCs) and T-cells. Recent studies suggest a key role of
      depressed T-cell derived interferon (IFN)-g in this complex immune cell
      interaction. The aim of this study was to elucidate further the underlying
      mechanisms responsible for dysfunctional T-cells and their interaction with APCs
      following trauma-hemorrhage. DESIGN: Adult C3H/HeN male mice were subjected to
      trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood
      pressure of 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. At 24
      h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via
      adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48
      h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific
      cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and
      granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in
      culture supernatants by Multiplex assay. The expression of MHC class II as well
      as co-stimulatory surface molecules on T-cells and APCs was determined by flow
      cytometry. RESULTS: The release of IL-4 and GM-CSF by T-cells was suppressed
      following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage
      APCs were present. Antigen-presenting cells from animals subjected to trauma
      hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In
      contrast, T-cells from trauma-hemorrhage animals depressed MHC class II
      expression of CD11c(+) cells, irrespective of whether APCs underwent sham or
      trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs
      (CD80, CD86) were not affected by trauma-hemorrhage. CONCLUSIONS: These results
      suggest that beside IFN-g other T-cell derived cytokines contribute to
      immunosuppression following trauma-hemorrhage causing diminished MHC II
      expression on APCs. Thus, T-cells appear to play an important role in this
      interaction at the time-point examined. Therapeutic approaches should aim at
      maintenance of T-cell function and their interaction with APCs to prevent
      extended immunosuppression following trauma-hemorrhage.

PMID- 19587000
TI  - Endotoxin-induced translocation of interleukin-6 from lungs to the systemic
      circulation.
AB  - It is widely postulated that systemic inflammation related to lung infections is
      largely caused by cytokine translocation from the lungs into the systemic
      circulation but there is a paucity of animal models to evaluate this hypothesis.
      In this proof-of-concept study, we developed a murine model to determine whether
      interleukin (IL)-6, a primary inflammatory cytokine, translocates following
      airway exposure to endotoxin. We collected central venous blood from the right
      atrium and arterial blood from the aorta simultaneously at 4 h and 24 h following
      intratracheal exposure to endotoxin (25 microg) and measured IL-6 in the serum
      and broncho-alveolar lavage (BAL) fluid (n = 33 mice). We repeated the experiment
      following 3 d of treatment with dexamethasone (n = 31 mice). Without stimulation,
      there was no significant arteriovenous gradient (3 pg/ml with interquartile range
      [IQR] of 3-5 pg/ml in arterial versus 18 pg/ml with IQR of 8-24 pg/ml in venous
      serum; P = 0.86). A significant arteriovenous difference was observed by 4 h post
      exposure to endotoxin (2813 pg/ml with IQR of 1578-4316 pg/ml in arterial versus
      1282 pg/ml with IQR of 778-2699 pg/ml in venous serum; P50.0001). The rise in the
      BAL IL-6 levels correlated with the increases in the arterial serum levels
      (P50.0001). Administration of intraperitoneal dexamethasone for 3 d attenuated
      the increased arteriovenous gradient. This murine model facilitates the
      estimation of cytokine translocation across the lungs and evaluation of compounds
      to modulate this gradient.

PMID- 19587001
TI  - Lipopolysaccharide induces alteration of serotonin transporter in human
      intestinal epithelial cells.
AB  - Intestinal serotoninergic activity and serotonin transporter (SERT) function have
      been shown to be altered in intestinal inflammatory diseases. Serotonin (5-HT)
      plays a critical role in the regulation of gastrointestinal physiology. Activity
      of 5-HT depends on its extracellular availability, partly modulated by SERT that
      transports 5-HT into the cell. Lipopolysaccharide (LPS) is a component of Gram
      negative bacteria outer membrane, which acts as a potent activator of the
      inflammatory system in the intestine. The aim of this work was to determine, in
      the enterocyte-like cell line Caco-2, whether LPS treatment affects
      serotoninergic activity by acting on SERT. The results demonstrate that LPS
      treatment diminishes SERT activity in a dose- and period-dependent way. The
      kinetic study shows that V(max) was significantly reduced after treatment with
      LPS. The LPS effect on 5-HT uptake was, in part, mediated by protein kinase C
      (PKC) activation. The molecular expression of SERT revealed that LPS treatment
      did not affect the mRNA level or the SERT protein content in cell homogenate. The
      level of SERT protein, however, was reduced on brush border membrane. The LPS
      effect might be due to an alteration of the intracellular traffic of SERT which
      may, in part, be mediated by PKC activity.

PMID- 19587002
TI  - NOD1 gene polymorphisms in relation to aggressive periodontitis.
AB  - BACKGROUND: NOD proteins are part of innate immunity mechanisms. They play a role
      in epithelial barrier functions and inflammatory responses to bacteria. Single
      nucleotide polymorphisms (SNPs) in the NOD1 gene have proven to be associated
      with inflammatory bowel disease (IBD) and asthma. OBJECTIVE: To investigate SNPs
      in the NOD1 gene in relation to aggressive periodontitis (AgP), a multifactorial,
      inflammatory disease of the supporting tissues of the teeth. MATERIALS AND
      METHODS: Five SNPs in the NOD1 gene (4 intronic and 1 exonic) were tested for
      association in a total of 415 AgP patients and 874 controls both of Northern
      European ancestry. RESULTS: The frequencies of the rare SNP alleles ranged
      between 21% and 26% among cases, and 20-27% among controls, and were not
      statistically different between cases and controls. Two SNPs were in strong
      linkage disequilibrium (r(2) = 0.97 in cases and 0.94 in controls). The overall
      haplotype distributions did not differ between cases and controls. We observed 8
      haplotypes with a frequency of >or=1% among cases and/or controls, but none of
      these haplotype frequencies differed significantly among cases and controls.
      Logistic regression analyses with adjustment for gender and smoking status did
      not reveal significant associations with AgP for any of the 5 SNPs. This study
      had a power of >or=95% to detect associations with variants carrying relative
      risks of >or=1.5 for heterozygote carriers and >or=2.25 for homozygote carriers.
      CONCLUSIONS: Although SNPs in the NOD1 gene have been strongly associated with
      cases of IBD, the current study failed to show an association of NOD1 SNPs with
      AgP.

PMID- 19587003
TI  - Replication or death: distinct fates of pathogenic Leptospira strain Lai within
      macrophages of human or mouse origin.
AB  - Pathogenic leptospires evoke severe diseases in humans but only cause mild
      chronic or asymptomatic infection in many host animals. The reasons for this
      diversity of infection remain unclear. Here, we demonstrated that Leptospira
      interrogans serovar Lai strain Lai had a similar ability to adhere to and enter
      primary and immortal (THP-1 and J774A.1) macrophages from human and mouse, but
      its intracellular fate in human macrophages differed markedly from that in mouse.
      The leptospires resided within membrane-bound vacuoles in the murine macrophages,
      but occurred free in the cytosol of human macrophages, with no surrounding
      vesicular membrane. Most leptospires in murine macrophages co-localized with the
      late-endosomal/lysosomal marker LAMP-1 and then were killed by lysosomal
      hydrolases, while most leptospires in human macrophages did not co-localize with
      this marker and survived. Enumeration of colony-forming units plus quantitative
      fluorimetry showed that in human, but not in murine, macrophages, the amounts of
      leptospires increased with incubation time. The infected human macrophages
      differed from mouse macrophages by displaying gradually enhanced apoptosis, in
      parallel with the increase in number of leptospires. These data strongly suggest
      that the outcome for intracellular leptospires depends on differences among host
      macrophages, which may account for some of the differences in the severity of
      leptospirosis in humans and animals.

PMID- 19587004
TI  - Processing of two latent membrane protein 1 MHC class I epitopes requires
      tripeptidyl peptidase II involvement.
AB  - The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential
      target for T cell immunotherapy in EBV-related malignancies. However, only a few
      CD8(+) T cell epitopes are known, and the benefit of LMP1-specific T cell
      immunotherapy has not yet been proven. In this work, we studied the processing of
      the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL. We found that
      target cells endogenously expressing the native LMP1 are not recognized by CTLs
      specific for these epitopes because the N-terminal part of LMP1 limits the
      efficiency of epitope generation. We further observed that the proteasome is not
      required for the generation of both epitopes and that the YLLEMLRWL epitope seems
      to be destroyed by the proteasome, because blocking of proteasomal activities
      enhanced specific CTL activation. Activation of LMP1-specific CTLs could be
      significantly reduced after inhibition of the tripeptidyl peptidase II,
      suggesting a role for this peptidase in the processing of both epitopes. Taken
      together, our results demonstrate that the MHC class I-restricted LMP1 epitopes
      studied in this work are two of very few epitopes known to date to be processed
      proteasome independently by tripeptidyl peptidase II.

PMID- 19587005
TI  - NKG2D-dependent IL-17 production by human T cells in response to an intracellular
      pathogen.
AB  - We studied the factors that control IL-17 production in human Mycobacterium
      tuberculosis infection. CD4(+) cells from healthy tuberculin reactors produced IL
      17 in response to autologous M. tuberculosis-stimulated monocytes, and most IL
      17(+) cells were Ag experienced, CD4(+)CD62L(-). IL-17 production by CD4(+) cells
      was inhibited by anti-IL-23, but not by Abs to IL-1, IL-6, or TGF-beta. Anti
      NKG2D reduced IL-17 production and the frequency of CD4(+)CD62(-) IL-17(+) cells,
      suggesting that NKG2D stimulates IL-17 production. CD4(+)NKG2D(+) cells did not
      produce IL-17. Monocytes and alveolar macrophages from healthy donors produced IL
      23 in response to M. tuberculosis. Addition of CD4(+) cells markedly enhanced IL
      23 production by M. tuberculosis-stimulated monocytes, and this was inhibited by
      anti-NKG2D and by Abs to UL-16 binding protein (ULB)1, a ligand for NKG2D on
      APCs. We conclude that binding of NKG2D to UL-16 binding protein (ULB)1
      contributes to IL-23-dependent IL-17 production by CD4(+) cells in human M.
      tuberculosis infection.

PMID- 19587007
TI  - Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory
      cytokine and type I IFN production in macrophages.
AB  - Inappropriate activation of TLR9 has been found to be involved in the
      pathogenesis of autoimmune diseases such as systemic lupus erythematosus. TLR9
      antagonists have been proposed to be therapeutic for some kinds of autoimmune
      diseases. In contrast, new negative regulators of TLR9 signal pathway need to be
      identified, and the mechanisms for the control of TLR9 response need to be fully
      investigated. It is well known that TLR9 will be finally transported to late
      endosome/lysosome once activated; however, the exact mechanism and the biological
      significance of the redistribution have not been fully elucidated. Ras related in
      brain (Rab)7b is a small guanosine triphosphatase, identified by us before, which
      is mainly localized in late endosome/lysosome. Our previous study shows that
      Rab7b can negatively regulate TLR4 signaling by promoting lysosomal degradation
      of TLR4. In this study, we show that TLR9 ligation can inhibit Rab7b expression
      in macrophages via ERK and p38 activation. In turn, the late endosome/lysosome
      localized Rab7b can colocalize with TLR9 in lysosomal-associated membrane protein
      1-positive compartment and down-regulate the expression of the TLR9 in
      macrophages by promoting TLR9 degradation once TLR9 is activated. Accordingly,
      Rab7b can negatively regulate TLR9-triggered production of TNF-alpha, IL-6, and
      IFN-beta in macrophages by impairing activation of MAPKs and NF-kappaB pathways.
      Our results suggest that the late endosome/lysosome-localized Rab7b can down
      regulate TLR9-triggered proinflammatory cytokine and type I IFN production by
      impairing TLR9 signaling via promotion of TLR9 degradation.

PMID- 19587006
TI  - NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and
      HMGB1 release via inflammasome-dependent and -independent pathways.
AB  - Bacterial infection elicits a range of beneficial as well as detrimental host
      inflammatory responses. Key among these responses are macrophage/monocyte
      necrosis, release of the proinflammatory factor high-mobility group box 1 protein
      (HMGB1), and induction of the cytokine IL-1. Although the control of IL-1beta has
      been well studied, processes that control macrophage cell death and HMGB1 release
      in animals are poorly understood. This study uses Klebsiella pneumonia as a model
      organism because it elicits all three responses in vivo. The regulation of these
      responses is studied in the context of the inflammasome components NLRP3 and ASC,
      which are important for caspase-1 activation and IL-1beta release. Using a
      pulmonary infection model that reflects human infection, we show that K.
      pneumonia-induced mouse macrophage necrosis, HMGB1, and IL-1beta release are
      dependent on NLRP3 and ASC. K. pneumoniae infection of mice lacking Nlrp3 results
      in decreased lung inflammation and reduced survival relative to control,
      indicating the overall protective role of this gene. Macrophage/monocyte necrosis
      and HMGB1 release are controlled independently of caspase-1, suggesting that the
      former two responses are separable from inflammasome-associated functions. These
      results provide critical in vivo validation that the physiologic role of NLRP3
      and ASC is not limited to inflammasome formation.

PMID- 19587008
TI  - Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop.
AB  - Type I IFNs play an important, yet poorly characterized, role in systemic lupus
      erythematosus. To better understand the interplay between type I IFNs and the
      activation of autoreactive B cells, we evaluated the effect of type I IFN
      receptor (IFNAR) deficiency in murine B cell responses to common TLR ligands. In
      comparison to wild-type B cells, TLR7-stimulated IFNAR(-/-) B cells proliferated
      significantly less well and did not up-regulate costimulatory molecules. By
      contrast, IFNAR1(-/-) B cells did not produce cytokines, but did proliferate and
      up-regulate activation markers in response to other TLR ligands. These defects
      were not due to a difference in the distribution of B cell populations or a
      failure to produce a soluble factor other than a type I IFN. Instead, the
      compromised response pattern reflected the disruption of an IFN-beta feedback
      loop and constitutively low expression of TLR7 in the IFNAR1(-/-) B cells. These
      results highlight subtle differences in the IFN dependence of TLR7 responses
      compared with other TLR-mediated B cell responses.

PMID- 19587010
TI  - The mechanism of osteoclast differentiation induced by IL-1.
AB  - IL-1 is a potent cytokine that can induce bone erosion in inflammatory sites such
      as rheumatoid joint regions via activation of osteoclasts. Not only is IL-1
      capable of activating osteoclasts, but it is also a key cytokine involved in the
      differentiation, multinucleation, and survival of osteoclasts. Herein, we show
      that IL-1 has the potential to drive osteoclast differentiation via a receptor
      activator of NF-kappaB ligand (RANKL)/RANK-independent mechanism. Although IL-1
      has a synergistic effect on RANKL-induced osteoclast formation, IL-1 alone cannot
      induce osteoclast differentiation from osteoclast precursors (bone marrow-derived
      macrophages (BMMs)) due to a lack of IL-1 signaling potential in these cells.
      However, we demonstrate that overexpression of the IL-1RI receptor in BMMs or
      induction of IL-1RI by c-Fos overexpression enables IL-1 alone to induce the
      formation of authentic osteoclasts by a RANKL/RANK-independent mechanism. The
      expression of IL-1RI is up-regulated by RANKL via c-Fos and NFATc1. Furthermore,
      the addition of IL-1 to IL-1RI overexpressing BMMs (IL-1/IL-1RI) strongly
      activates NF-kappaB, JNK, p38, and ERK which is a hallmark gene activation
      profile of osteoclastogenesis. Interestingly, IL-1/IL-1RI does not induce
      expression of c-Fos or NFATc1 during osteoclast differentiation, although basal
      levels of c-Fos and NFATc1 seem to be required. Rather, IL-1/IL-1RI strongly
      activates MITF, which subsequently induces osteoclast-specific genes such as
      osteoclast-associated receptor and tartrate-resistant acid phosphatase. Together,
      these results reveal that IL-1 has the potential to induce osteoclast
      differentiation via activation of microphthalmia transcription factor under
      specific microenvironmental conditions.

PMID- 19587009
TI  - Inflamed lymphatic endothelium suppresses dendritic cell maturation and function
      via Mac-1/ICAM-1-dependent mechanism.
AB  - The lymphatic system is essential for the generation of immune responses by
      facilitating immune cell trafficking to lymph nodes. Dendritic cells (DCs), the
      most potent APCs, exit tissues via lymphatic vessels, but the mechanisms of
      interaction between DCs and the lymphatic endothelium and the potential
      implications of these interactions for immune responses are poorly understood. In
      this study, we demonstrate that lymphatic endothelial cells (LECs) modulate the
      maturation and function of DCs. Direct contact of human monocyte-derived DCs with
      an inflamed, TNF-alpha-stimulated lymphatic endothelium reduced expression of the
      costimulatory molecule CD86 by DCs and suppressed the ability of DCs to induce T
      cell proliferation. These effects were dependent on adhesive interactions between
      DCs and LECs that were mediated by the binding of Mac-1 on DCs to ICAM-1 on LECs.
      Importantly, the suppressive effects of the lymphatic endothelium on DCs were
      observed only in the absence of pathogen-derived signals. In vivo, DCs that
      migrated to the draining lymph nodes upon inflammatory stimuli, but in the
      absence of a pathogen, showed increased levels of CD86 expression in ICAM-1
      deficient mice. Together, these data demonstrate a direct role of LECs in the
      modulation of immune response and suggest a function of the lymphatic endothelium
      in preventing undesired immune reactions in inflammatory conditions.

PMID- 19587011
TI  - The lytic potential of human liver NK cells is restricted by their limited
      expression of inhibitory killer Ig-like receptors.
AB  - The human liver is enriched in NK cells which are potent effectors of the innate
      immune system. We have determined that liver NK cells freshly isolated from
      surgical specimens from patients with hepatic malignancy have less cytolytic
      activity than autologous blood NK cells. This difference was due to a higher
      proportion of CD16(-) NK cells in the liver and reduced cytotoxicity by CD16(+)
      liver NK cells compared with their blood counterparts. CD16(+) liver NK cells had
      similar expression of activating NK receptors and had similar intracellular
      granzyme B and perforin content compared with CD16(+) blood NK cells. CD16(+)
      liver NK cells contained a reduced fraction of cells with inhibitory killer Ig
      like receptors specific for self-MHC class I (self-killer Ig-related receptor
      (KIR)) and an increased fraction of self-KIR(neg)NKG2A(pos) and self
      KIR(neg)NKG2A(neg) cells. Using single-cell analysis of intracellular IFN-gamma
      production and cytotoxicity assays, we determined that CD16(+) liver NK cells
      expressing self-KIR were more responsive to target cells than those cells that
      did not express self-KIR molecules. CD16(+) liver NK cells gained cytolytic
      function when stimulated with IL-2 or cultured with LPS or poly(I:C)-activated
      autologous liver Kupffer cells. Thus, the human liver contains NK cell subsets
      which have reduced effector function, but under appropriate inflammatory
      conditions become potent killers.

PMID- 19587013
TI  - Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid
      receptor-related orphan receptor (gamma)t+ and respond preferentially under
      inflammatory conditions.
AB  - Lymph nodes (LNs) have been long considered as comprising few invariant NKT
      (iNKT) cells, and these cells have not been studied extensively. In this study,
      we unravel the existence of stable rather than transitional LN-resident NK1.1(-)
      iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to
      comprise a major IL-17-producing population and to express the retinoic acid
      receptor-related orphan receptor (gamma)t (ROR(gamma)t). These cells respond to
      their ligand alpha-galactosylceramide (alpha-GalCer) in vivo by expanding
      dramatically in the presence of LPS, providing insight into how this rare
      population could have an impact in immune responses to infection. PLN-resident
      ROR(gamma)t(+) NK1.1(-) iNKT cells express concomitantly CCR6, the integrin alpha
      chain alpha(E) (CD103), and IL-1R type I (CD121a), indicating that they might
      play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major
      ROR(gamma)t(+) CCR6(+)CD103(+)CD121a(+) NK1.1(-) cell population, reflecting iNKT
      cell composition in PLNs. Importantly, both skin and draining PLN ROR(gamma)t(+)
      iNKT cells respond preferentially to inflammatory signals and independently of IL
      6, indicating that they could play a nonredundant role during inflammation.
      Overall, our study indicates that ROR(gamma)t(+) iNKT cells could play a major
      role in the skin during immune responses to infection and autoimmunity.

PMID- 19587012
TI  - Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide.
AB  - Regulatory T cells (Tregs) play a pivotal role in the maintenance of homeostasis
      between immune response and immune tolerance. The transcription factor Foxp3 and
      the surface protein CD25 are the two key molecules characterizing Tregs. In
      autoimmune and various other chronic inflammatory diseases, the expression of
      Foxp3 is severely down-regulated. However, the molecular mechanism underlying the
      down-regulation of Foxp3 is not understood yet. Because the IL-12p40 homodimer
      (p40(2)) is markedly up-regulated in response to various inflammatory stimuli,
      the present study was undertaken to explore the role of p40(2) in the regulation
      of Foxp3 in naive mouse splenocytes. IL-12p40(2) dose-dependently inhibited the
      expression of Foxp3 and CD25, but not CD4. Interestingly, this inhibition was
      absent in splenocytes of IL-12Rbeta1(-/-), but not IL-12Rbeta2(-/-), mice.
      Moreover, suppression of Foxp3 in wild-type and IL-12Rbeta2(-/-) splenocytes was
      accompanied by production of NO. Consistently, l-N(6)-(1-iminoethyl)-lysine
      hydrochloride, an inhibitor of inducible NO synthase (iNOS), and PTIO, a
      scavenger of NO, restored the expression of Foxp3 and CD25 in p40(2)-stimulated
      splenocytes, and p40(2) was unable to down-regulate Foxp3 and CD25 in splenocytes
      from iNOS(-/-) mice. Furthermore, NO, but not p40(2), was able to inhibit Foxp3
      in purified CD4(+)CD25(+) T cells in the absence of iNOS-expressing cells. Hence,
      our results clearly demonstrate that p40(2) induces NO production via IL-12Rbeta1
      and that NO subsequently suppresses Tregs in naive mouse splenocytes. This study,
      therefore, delineates an unprecedented biological function of p40(2) in the
      regulation of Foxp3 via IL-12Rbeta1-mediated NO production.

PMID- 19587014
TI  - The CCL7-CCL2-CCR2 axis regulates IL-4 production in lungs and fungal immunity.
AB  - Expression of the chemokine receptor CCR2 can be detrimental or beneficial for
      infection resolution. Herein, we examined whether CCR2 was requisite for control
      of infection by the dimorphic fungus Histoplasma capsulatum. H. capsulatum
      infected CCR2(-/-) mice manifested defects in inflammatory cell recruitment,
      increased IL-4, and progressive infection. Increased IL-4 in CCR2(-/-) mice
      primarily contributed to decreased host resistance as demonstrated by the ability
      of IL-4-neutralized CCR2(-/-) mice to resolve infection without altering
      inflammatory cell recruitment. Surprisingly, numerous alveolar macrophages and
      dendritic cells contributed to IL-4 production in CCR2(-/-) mice. IL-4-mediated
      impairment of immunity in CCR2(-/-) mice was associated with increased arginase-1
      and YM1 transcription and increased transferrin receptor expression by phagocytic
      cells. Immunity in mice lacking the CCR2 ligand CCL2 was not impaired despite
      decreased inflammatory cell recruitment. Neutralization of the CCR2 ligand CCL7
      in CCL2(-/-) mice, but not wild type, resulted in increased IL-4 and fungal
      burden. Thus, CCL7 in combination with CCL2 limits IL-4 generation and exerts
      control of host resistance. Furthermore, increased phagocyte-derived IL-4 in
      CCR2(-/-) mice is associated with the presence of alternatively activated
      phagocytic cells.

PMID- 19587015
TI  - B and T lymphocyte attenuator tempers early infection immunity.
AB  - Coinhibitory pathways are thought to act in later stages of an adaptive immune
      response, but whether coinhibition contributes to early innate immunity is
      unclear. We show that engagement of the newly discovered coinhibitory receptor B
      and T lymphocyte attenuator (BTLA) by herpesvirus entry mediator (HVEM) is
      critical for negatively regulating early host immunity against intracellular
      bacteria. Both HVEM(-/-) and BTLA(-/-), but not LIGHT(-/-), mice are more
      resistant to listeriosis compared with wild-type mice, and blockade of the BTLA
      pathway promotes, while engagement inhibits, early bacterial clearance.
      Differences in bacterial clearance were seen as early as 1 day postinfection,
      implicating the initial innate response. Therefore, innate cell function in BTLA(
      /-) mice was studied. We show that innate cells from BTLA(-/-) mice secrete
      significantly more proinflammatory cytokines upon stimulation with heat-killed
      Listeria. These results provide the first evidence that a coinhibitory pathway
      plays a critical role in regulating early host innate immunity against infection.

PMID- 19587016
TI  - Tissue-specific abundance of regulatory T cells correlates with CD8+ T cell
      dysfunction and chronic retrovirus loads.
AB  - Infection of mice with Friend virus induces the activation of CD4(+) regulatory T
      cells (Tregs) that suppress virus-specific CD8(+) T cells. This suppression leads
      to incomplete virus clearance and the establishment of virus persistence. We now
      show that Treg-mediated suppression of CD8(+) T cells is tissue specific,
      occurring in the spleen but not the liver. Regardless of infection status, there
      was a 5-fold lower proportion of Tregs in the liver than in the spleen, much
      lower absolute cell numbers, and the relatively few Tregs present expressed less
      CD25. Results indicated that reduced expression of CD25 on liver Tregs was due to
      microenvironmental factors including low levels of IL-2 production by CD4(+) Th
      cells in that tissue. Low CD25 expression on liver Tregs did not impair their
      ability to suppress CD8(+) T cells in vitro. Correlating with the decreased
      proportion of Tregs in the liver was a significantly increased proportion of
      virus-specific CD8(+) T cells compared with the spleen. The virus-specific CD8(+)
      T cells from the liver did not appear suppressed given that they produced both
      IFN-gamma and granzyme B, and they also showed evidence of recent cytolytic
      activity (CD107a(+)). The functional phenotype of the virus-specific CD8(+) T
      cells correlated with a 10-fold reduction of chronic Friend virus levels in the
      liver compared with the spleen. Thus, suppression of CD8(+) T cells by virus
      induced Tregs occurs in a tissue-specific manner and correlates with profound
      effects on localized levels of chronic infection.

PMID- 19587018
TI  - Infection with a helminth parasite attenuates autoimmunity through TGF-beta
      mediated suppression of Th17 and Th1 responses.
AB  - The lower incidence of allergy and autoimmune diseases in developing countries
      has been associated with a high prevalence of parasitic infections. Here we
      provide direct experimental evidence that parasites can exert bystander
      immunosuppression of pathogenic T cells that mediate autoimmune diseases.
      Infection of mice with Fasciola hepatica resulted in recruitment of dendritic
      cells, macrophages, eosinophils, neutrophils, and CD4(+) T cells into the
      peritoneal cavity. The dendritic cells and macrophages in infected mice expressed
      IL-10 and latency-associated peptide, and they had low surface expression of
      costimulatory molecules and/or MHC class II. Furthermore, most CD4(+) T cells in
      the peritoneal cavity of infected mice secreted IL-10, but not IFN-gamma or IL-4.
      There was a less significant expansion of CD4(+)Foxp3(+) T cells. F. hepatica
      specific Tr1-type clones generated from infected mice suppressed proliferation
      and IFN-gamma production by Th1 cells. Infection was associated with suppression
      of parasite-specific Th1 and Th2 responses, which was reversed in IL-10-defective
      mice. Infection with F. hepatica also exerted bystander suppression of immune
      responses to autoantigens and attenuated the clinical signs of experimental
      autoimmune encephalomyelitis. Protection was associated with suppression of
      autoantigen-specific IFN-gamma and IL-17 production. The suppression of Th1 and
      Th17 responses and attenuation of experimental autoimmune encephalomyelitis by F.
      hepatica was maintained in IL-10(-/-) mice but was reversed by neutralization of
      TGF-beta in vivo. Our study provides evidence that F. hepatica-induced IL-10
      subverts parasite-specific Th1 and Th2 responses, but that F. hepatica-induced
      TGF-beta plays a critical role in bystander suppression of autoantigen-specific
      Th1 and Th17 responses that mediate autoimmune diseases.

PMID- 19587017
TI  - STAT1 negatively regulates lung basophil IL-4 expression induced by respiratory
      syncytial virus infection.
AB  - IL-4 contributes to immunopathology induced in mice by primary respiratory
      syncytial virus (RSV) infection. However, the cellular source of IL-4 in RSV
      infection is unknown. We identified CD3(-)CD49b(+) cells as the predominant
      source of IL-4 in the lungs of RSV-infected BALB/c mice. We ruled out T cells, NK
      cells, NKT cells, mast cells, and eosinophils as IL-4 expressors in RSV infection
      by flow cytometry. Using IL4 GFP reporter mice (4get) mice, we identified the IL
      4-expressing cells in RSV infection as basophils (CD3(-)CD49b(+)FcepsilonRI(+)c
      kit(-)). Because STAT1(-/-) mice have an enhanced Th2-type response to RSV
      infection, we also sought to determine the cellular source and role of IL-4 in
      RSV-infected STAT1(-/-) mice. RSV infection resulted in significantly more IL-4
      expressing CD3(-)CD49b(+) cells in the lungs of STAT1(-/-) mice than in BALB/c
      mice. CD49b(+)IL-4(+) cells sorted from the lungs of RSV-infected STAT1(-/-) mice
      and stained with Wright-Giemsa had basophil characteristics. As in wild-type
      BALB/c mice, IL-4 contributed to lung histopathology in RSV-infected STAT1(-/-)
      mice. Depletion of basophils in RSV-infected STAT1(-/-) mice reduced lung IL-4
      expression. Thus, we show for the first time that a respiratory virus (RSV)
      induced basophil accumulation in vivo. Basophils were the primary source of IL-4
      in the lung in RSV infection, and STAT1 was a negative regulator of virus-induced
      basophil IL-4 expression.

PMID- 19587019
TI  - A critical role for REV1 in regulating the induction of C:G transitions and A:T
      mutations during Ig gene hypermutation.
AB  - REV1 is a deoxycytidyl transferase that catalyzes the incorporation of
      deoxycytidines opposite deoxyguanines and abasic sites. To explore the role of
      its catalytic activity in Ig gene hypermutation in mammalian cells, we have
      generated mice expressing a catalytically inactive REV1 (REV1AA). REV1AA mice
      developed normally and were fertile on a pure C57BL/6 genetic background. B and T
      cell development and maturation were not affected, and REV1AA B cells underwent
      normal activation and class switch recombination. Analysis of Ig gene
      hypermutation in REV1AA mice revealed a great decrease of C to G and G to C
      transversions, consistent with the disruption of its deoxycytidyl transferase
      activity. Intriguingly, REV1AA mice also exhibited a significant reduction of C
      to T and G to A transitions. Moreover, each type of nucleotide substitutions at
      A:T base pairs was uniformly reduced in REV1AA mice, a phenotype similar to that
      observed in mice haploinsufficient for Polh. These results reveal an unexpected
      role for REV1 in the generation of C:G transitions and A:T mutations and suggest
      that REV1 is involved in multiple mutagenic pathways through functional
      interaction with other polymerases during the hypermutation process.

PMID- 19587020
TI  - Distinct requirements for CD1d intracellular transport for development of
      V(alpha)14 iNKT cells.
AB  - The positive selection of V(alpha)14 invariant (i)NKT cells in mice requires CD1d
      mediated Ag presentation by CD4(+)CD8(+) thymocytes. Maturation of newly selected
      iNKT cells continues in the periphery and also involves CD1d expression. CD1d
      molecules acquire Ags for presentation in endosomal compartments, to which CD1d
      molecules have access through an intrinsic CD1d-encoded tyrosine motif and by
      association with the class II MHC chaperone, invariant chain. In this study, we
      report the generation of mice in which all CD1d is replaced by CD1d-enhanced
      yellow fluorescent fusion protein (EYFP). CD1d-EYFP molecules are stable, present
      lipid Ags, and have near normal subcellular distribution. CD1d-EYFP molecules
      mediated positive selection of V(alpha)14 iNKT cell precursors at decreased
      efficiency, caused a delay in their terminal maturation, and did not invoke
      V(alpha)14iNKT cell effector function as wild-type CD1d could. Using these mice,
      we show that the intrinsic CD1d-encoded sorting motif mediates thymic selection
      and activation of V(alpha)14 iNKT cells by professional APCs, while for
      peripheral terminal differentiation the intrinsic CD1d sorting motif is
      dispensable.

PMID- 19587022
TI  - Lack of CD200 enhances pathological T cell responses during influenza infection.
AB  - Influenza virus infection can be accompanied by life-threatening immune pathology
      most likely due to excessive antiviral responses. Inhibitory immune receptors may
      restrain such overactive immune responses. To study the role of the inhibitory
      immune receptor CD200R and its ligand CD200 during influenza infection, we
      challenged wild-type and CD200(-/-) mice with influenza virus. We found that
      CD200(-/-) mice in comparison to wild-type controls when inoculated with
      influenza virus developed more severe disease, associated with increased lung
      infiltration and lung endothelium damage. CD200(-/-) mice did develop adequate
      adaptive immune responses and were able to control viral load, suggesting that
      the severe disease was caused by a lack of control of the immune response.
      Interestingly, development of disease was completely prevented by depletion of T
      cells before infection, despite dramatically increased viral load, indicating
      that T cells are essential for the development of disease symptoms. Our data show
      that lack of CD200-CD200R signaling increases immune pathology during influenza
      infection, which can be reduced by T cell depletion.

PMID- 19587021
TI  - IL-13 receptor alpha2 regulates the immune and functional response to
      Nippostrongylus brasiliensis infection.
AB  - IL-13 has a prominent role in host defense against the gastrointestinal nematode
      Nippostrongylus brasiliensis; however, the role of IL-13Ralpha2 in the immune and
      functional response to enteric infection is not known. In the current study, we
      investigated changes in smooth muscle and epithelial cell function as well as
      alterations in gene expression of IL-13 and IL-4 and their receptors using laser
      capture microdissection of specific cell types in the small intestine of N.
      brasiliensis-infected mice. An infection-induced up-regulation of IL-13Ralpha2
      gene expression was confined to smooth muscle and was dependent on STAT6 and IL
      13, but not on IL-4. In contrast, expression of IL-13Ralpha1 was reduced,
      indicating that changes in IL-13alpha2 expression serve to limit the biological
      effects of IL-13. The increased availability of IL-13 in IL-13Ralpha2(-/-) mice
      resulted in marked changes in constitutive epithelial and smooth muscle function.
      In addition, maximal changes in smooth muscle hypercontractility and epithelial
      cell resistance peaked earlier after infection in IL-13Ralpha2(-/-) compared with
      wild-type mice. This did not coincide with an earlier Th2 immune response as
      expression of IL-4 and IL-13 was attenuated in IL-13Ralpha2(-/-) mice and worm
      expulsion was similar to that of wild-type mice. These data show that IL
      13Ralpha2 plays an important role in nematode infection by limiting the
      availability of IL-13 during infection, thereby regulating both the immune and
      biological effects of IL-13.

PMID- 19587023
TI  - Transforming growth factor beta promotes neuronal cell fate of mouse cortical and
      hippocampal progenitors in vitro and in vivo: identification of Nedd9 as an
      essential signaling component.
AB  - Transforming Growth Factor beta (Tgfbeta) and associated signaling effectors are
      expressed in the forebrain, but little is known about the role of this
      multifunctional cytokine during forebrain development. Using hippocampal and
      cortical primary cell cultures of developing mouse brains, this study identified
      Tgfbeta-regulated genes not only associated with cell cycle exit of progenitors
      but also with adoption of neuronal cell fate. Accordingly, we observed not only
      an antimitotic effect of Tgfbeta on progenitors but also an increased expression
      of neuronal markers in Tgfbeta treated cultures. This effect was dependent upon
      Smad4. Furthermore, in vivo loss-of-function analyses using Tgfbeta2(-/
      )/Tgfbeta3(-/-) double mutant mice showed the opposite effect of increased cell
      proliferation and fewer neurons in the cerebral cortex and hippocampus. Gata2,
      Runx1, and Nedd9 were candidate genes regulated by Tgfbeta and known to be
      involved in developmental processes of neuronal progenitors. Using siRNA-mediated
      knockdown, we identified Nedd9 as an essential signaling component for the
      Tgfbeta-dependent increase in neuronal cell fate. Expression of this scaffolding
      protein, which is mainly described as a signaling molecule of the beta1-integrin
      pathway, was not only induced after Tgfbeta treatment but was also associated
      with morphological changes of the Nestin-positive progenitor pool observed upon
      exposure to Tgfbeta.

PMID- 19587025
TI  - Morphometry of olfactory lamellae and olfactory receptor neurons during the life
      history of chum salmon (Oncorhynchus keta).
AB  - It is generally accepted that anadromous Pacific salmon (genus Oncorhynchus)
      imprint to odorants in their natal streams during their seaward migration and use
      olfaction to identify these during their homeward migration. Despite the
      importance of the olfactory organ during olfactory imprinting, the development of
      this structure is not well understood in Pacific salmon. Olfactory cues from the
      environment are relayed to the brain by the olfactory receptor neurons (ORNs) in
      the olfactory organ. Thus, we analyzed morphometric changes in olfactory lamellae
      of the peripheral olfactory organ and in the quantity of ORNs during life history
      from alevin to mature in chum salmon (Oncorhynchus keta). The number of lamellae
      increased markedly during early development, reached 18 lamellae per unilateral
      peripheral olfactory organ in young salmon with a 200 mm in body size, and
      maintained this lamellar complement after young period. The number of ORNs per
      olfactory organ was about 180,000 and 14.2 million cells in fry and mature
      salmon, respectively. The relationship between the body size (fork length) and
      number of ORNs therefore revealed an allometric association. Our results
      represent the first quantitative analysis of the number of ORNs in Pacific salmon
      and suggest that the number of ORNs is synchronized with the fork length
      throughout its life history.

PMID- 19587024
TI  - Alignment of multiple protein structures based on sequence and structure
      features.
AB  - Comparing the structures of proteins is crucial to gaining insight into protein
      evolution and function. Here, we align the sequences of multiple protein
      structures by a dynamic programming optimization of a scoring function that is a
      sum of an affine gap penalty and terms dependent on various sequence and
      structure features (SALIGN). The features include amino acid residue type,
      residue position, residue accessible surface area, residue secondary structure
      state and the conformation of a short segment centered on the residue. The
      multiple alignment is built by following the 'guide' tree constructed from the
      matrix of all pairwise protein alignment scores. Importantly, the method does not
      depend on the exact values of various parameters, such as feature weights and gap
      penalties, because the optimal alignment across a range of parameter values is
      found. Using multiple structure alignments in the HOMSTRAD database, SALIGN was
      benchmarked against MUSTANG for multiple alignments as well as against TM-align
      and CE for pairwise alignments. On the average, SALIGN produces a 15% improvement
      in structural overlap over HOMSTRAD and 14% over MUSTANG, and yields more
      equivalent structural positions than TM-align and CE in 90% and 95% of cases,
      respectively. The utility of accurate multiple structure alignment is illustrated
      by its application to comparative protein structure modeling.

PMID- 19587026
TI  - Changes in sweet taste across pregnancy in mild gestational diabetes mellitus:
      relationship to endocrine factors.
AB  - Gestational diabetes mellitus (GDM) is glucose intolerance diagnosed during
      pregnancy. Previous work suggested that women with GDM showed exaggerated
      preferences for sweet taste, but data were limited to a single time point during
      pregnancy. This study longitudinally assessed sweet taste changes across
      pregnancy in women who developed GDM (n = 15) as compared with women with normal
      glucose tolerance (NGT; n = 93) and nonpregnant controls (n = 19). A second
      objective was to relate sweet taste changes in GDM to fasting leptin and insulin
      profiles. Following an overnight fast, subjects evaluated strawberry-flavored
      milks varying in sucrose and fat content, as well as glucose solutions.
      Evaluations were made at 3 time points during pregnancy and during early
      postpartum. At 34-38 weeks gestation, women with GDM gave higher liking ratings
      to moderately sweetened (5% and 10% sucrose) strawberry milks than women with
      NGT. These differences were not related to alterations in the perception of the
      samples. At 24-28 weeks gestation, and in women with GDM only, fasting insulin
      was correlated with liking of the glucose solutions (R(2) = 0.63, P = 0.004) and
      fasting leptin was correlated with sweetness liking of the 10% sucrose milk (R(2)
      = 0.42, P = 0.017). These data suggest that women with GDM exhibit higher liking
      ratings for a sweet fat milk drink late in pregnancy. Also, higher hedonic
      ratings for sweet taste in GDM may be related to elevated leptin and insulin
      concentrations at midpregnancy. GDM may increase the desire for sweet taste that
      could influence dietary management of this disease.

PMID- 19587027
TI  - Reliability and validity of the Chinese version of the CARE Measure in a primary
      care setting in Hong Kong.
AB  - BACKGROUND: The Consultation and Relational Empathy (CARE) Measure is a validated
      patient-rated measure of consultation quality in the UK. OBJECTIVES: To provide
      preliminary evidence of the reliability and validity of a Chinese version of the
      CARE Measure in a primary care setting in Hong Kong. METHODS: Following
      translation, back-translation and pilot testing, a Chinese version of the CARE
      Measure was developed and tested on 253 unselected primary care patients in Hong
      Kong. RESULTS: The Chinese-CARE Measure was regarded by patients as being
      relevant to their consultations, with on average only 5.5% of patients rating the
      items as not important (range 3.6-10.2% for individual items), suggesting high
      acceptability and face validity. This was also supported by the relatively low
      number of 'not applicable' responses recorded for the measure (average 8.2%,
      range 0.4-21.7% for individual items). Internal reliability was high (Cronbach's
      alpha 0.962) and was reduced by the removal of any of the 10 items, and
      homogeneity was indicated by high corrected item-total correlations (0.786
      0.876). Factor analysis showed a single solution for the Chinese-CARE Measure
      items with high item loadings (0.821-0.891). Construct validity was further
      supported by significant hypothesized relationships with other variables (patient
      enablement and patient satisfaction). Consultation length and continuity of care
      were independent predictors of Chinese-CARE Measure score in stepwise multiple
      regression analysis but together explained <10% of variation in CARE score.
      CONCLUSION: These preliminary data support the reliability and validity of the
      Chinese version of the CARE Measure in primary care in Hong Kong.

PMID- 19587028
TI  - Physiological regulation of coccolith polysaccharide production by phosphate
      availability in the coccolithophorid Emiliania huxleyi.
AB  - Coccoliths of the coccolithophorid Emiliania huxleyi are calcified biomineral
      scales composed of calcium carbonate and coccolith polysaccharide (CPs).
      Coccolith production is regulated by inorganic phosphate (P(i)) availability, but
      no information currently exists on how this process occurs. In this study CP was
      experimentally characterized by HPLC analysis as an acid polysaccharide of
      mannose, galacturonic acid, xylose and rhamnose. Both calcification (estimated
      from 45Ca uptake) and CP production (estimated from uronic acid quantification)
      were stimulated under P(i)-deficient conditions but strongly suppressed under
      P(i)-sufficient conditions. When cells were transferred from P(i)-sufficient to
      P(i)-deficient conditions the production of neutral polysaccharides (NP)--storage
      glucans--ceased rapidly after a temporary increase in the presence of P(i), and
      CP production started to increase after P(i) was almost depleted. Under P(i)
      sufficient conditions NP production increased, concomitant with stimulation of
      cell growth. Calcification increased gradually, but photosynthetic 14CO2 fixation
      was reduced by almost 40% for 5 d of culture during P(i) depletion. [14C]CP
      production was maintained at almost constant, high levels under P(i)-deficient
      conditions but gradually decreased under P(i)-sufficient conditions in
      conjunction with cell growth. In contrast, [14C]NP production increased about 3
      fold under P(i)-sufficient conditions for 3 d. The present study indicates that
      E. huxleyi switches the direction of carbon flow toward CP and NP production
      under P(i)-deficient and P(i)-sufficient conditions, respectively.

PMID- 19587029
TI  - The genome of human parvovirus b19 can replicate in nonpermissive cells with the
      help of adenovirus genes and produces infectious virus.
AB  - Human parvovirus B19 (B19V) is a member of the genus Erythrovirus in the family
      Parvoviridae. In vitro, autonomous B19V replication is limited to human erythroid
      progenitor cells and in a small number of erythropoietin-dependent human
      megakaryoblastoid and erythroid leukemic cell lines. Here we report that the
      failure of B19V DNA replication in nonpermissive 293 cells can be overcome by
      adenovirus infection. More specifically, the replication of B19V DNA in the 293
      cells and the production of infectious progeny virus were made possible by the
      presence of the adenovirus E2a, E4orf6, and VA RNA genes that emerged during the
      transfection of the pHelper plasmid. Using this replication system, we identified
      the terminal resolution site and the nonstructural protein 1 (NS1) binding site
      on the right terminal palindrome of the viral genome, which is composed of a
      minimal origin of replication spanning 67 nucleotides. Plasmids or DNA fragments
      containing an NS1 expression cassette and this minimal origin were able to
      replicate in both pHelper-transfected 293 cells and B19V-semipermissive UT7/Epo
      S1 cells. Our results have important implications for our understanding of native
      B19V infection.

PMID- 19587031
TI  - Gag determinants of fitness and drug susceptibility in protease inhibitor
      resistant human immunodeficiency virus type 1.
AB  - Mutations can accumulate in the protease and gag genes of human immunodeficiency
      virus in patients who fail therapy with protease inhibitor drugs. Mutations
      within protease, the drug target, have been extensively studied. Mutations in gag
      have been less well studied, mostly concentrating on cleavage sites. A retroviral
      vector system has been adapted to study full-length gag, protease, and reverse
      transcriptase genes from patient-derived viruses. Patient plasma-derived mutant
      full-length gag, protease, and gag-protease from a multidrug-resistant virus were
      studied. Mutant protease alone led to a 95% drop in replication capacity that was
      completely rescued by coexpressing the full-length coevolved mutant gag gene.
      Cleavage site mutations have been shown to improve the replication capacity of
      mutated protease. Strikingly, in this study, the matrix region and part of the
      capsid region from the coevolved mutant gag gene were sufficient to achieve full
      recovery of replication capacity due to the mutant protease, without cleavage
      site mutations. The same region of gag from a second, unrelated, multidrug
      resistant clinical isolate also rescued the replication capacity of the original
      mutant protease, suggesting a common mechanism that evolves with resistance to
      protease inhibitors. Mutant gag alone conferred reduced susceptibility to all
      protease inhibitors and acted synergistically when linked to mutant protease. The
      matrix region and partial capsid region of gag sufficient to rescue replication
      capacity also conferred resistance to protease inhibitors. Thus, the amino
      terminus of Gag has a previously unidentified and important function in protease
      inhibitor susceptibility and replication capacity.

PMID- 19587030
TI  - Disruption of LANA in rhesus rhadinovirus generates a highly lytic recombinant
      virus.
AB  - Rhesus monkey rhadinovirus (RRV) is a gammaherpesvirus that is closely related to
      human Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). RRV is the closest
      relative to KSHV that has a fully sequenced genome and serves as an in vitro and
      an in vivo model system for KSHV. The latency-associated nuclear antigen (LANA)
      protein of both KSHV and RRV plays key roles in the establishment and maintenance
      of these herpesviruses. We have constructed a RRV recombinant virus
      (RRVDeltaLANA/GFP) in which the RRV LANA open reading frame has been disrupted
      with a green fluorescent protein (GFP) expression cassette generated by
      homologous recombination. The integrity of the recombinant virus was confirmed by
      diagnostic PCR, restriction digestion, Southern blot analysis, and whole-genome
      sequencing. We compared the single-step and multistep replication kinetics of
      RRVDeltaLANA/GFP, RRV-GFP, wild-type (WT) RRV H26-95, and a revertant virus using
      traditional plaque assays, as well as real-time quantitative PCR-based genome
      quantification assays. The RRVDeltaLANA/GFP recombinant virus exhibited
      significantly higher lytic replicative properties compared to RRV-GFP, WT RRV, or
      the revertant virus. This was observed upon de novo infection and in the absence
      of chemical inducers such as phorbol esters. In addition, by using a quantitative
      real-time PCR-based viral array, we are the first to report differences in global
      viral gene expression between WT and recombinant viruses. The RRVDeltaLANA/GFP
      virus displayed increased lytic gene transcription at all time points
      postinfection compared to RRV-GFP. Moreover, we also examined several cellular
      genes that are known to be repressed by KSHV LANA and report that these genes are
      derepressed during de novo lytic infection with the RRVDeltaLANA/GFP virus
      compared to RRV-GFP. Finally, we also demonstrate that the RRVDeltaLANA/GFP virus
      fails to establish latency in B cells, as measured by the loss of GFP-positive
      cells and intracellular viral genomes.

PMID- 19587032
TI  - Role for the paramyxovirus genomic promoter in limiting host cell antiviral
      responses and cell killing.
AB  - The parainfluenza virus simian virus 5 (SV5) is a poor inducer of innate immune
      responses. In contrast, the naturally occurring SV5 variant Wake Forest
      parainfluenza virus (WF-PIV) activates the synthesis of proinflammatory cytokines
      and beta interferon (IFN-beta). Comparison of SV5 and WF-PIV genome sequences
      revealed nine nucleotide differences within the viral genomic promoter, including
      two substitutions (U5C and A14G) in the most highly conserved 3'-end promoter
      element. To test the consequences of these promoter variations, a recombinant SV5
      mutant [Le-(U5C, A14G)] was engineered to harbor the two WF-PIV genomic promoter
      substitutions in an otherwise wild-type (WT) SV5 background. Human lung
      epithelial cells infected with the Le-(U5C, A14G) mutant had higher rates of
      viral protein synthesis and levels of mRNA than cells infected with WT SV5, but
      levels of genomic RNA were not changed. Unlike WT SV5, the Le-(U5C, A14G) mutant
      was a potent inducer of interleukin-6 and IFN-beta synthesis, despite expressing
      a functional V protein antagonist. Cytokine responses to Le-(U5C, A14G) infection
      were reduced either by small interfering RNA-mediated knockdown of retinoic acid
      inducible gene I (RIG-I) or after infection of cells that were engineered to
      express the reovirus sigma3 double-stranded RNA-binding protein. Le-(U5C, A14G)
      induced cytopathic effects not seen with WT SV5, and the extent of cell killing
      correlated with elevated levels of viral F protein and cell-cell fusion. Our
      results support a model whereby the SV5 promoter has evolved to function at an
      attenuated level in order to limit (i) synthesis of aberrant RNAs which induce
      RIG-I-mediated responses and (ii) overproduction of mRNA for potentially toxic
      gene products, such as the F protein. Control of genomic promoter activity may be
      particularly important for viruses such as SV5, that express a V protein
      targeting mda-5 but do not encode antagonists such as the paramyxovirus C
      proteins, that specifically target RIG-I.

PMID- 19587033
TI  - Vesicular stomatitis virus induces apoptosis primarily through Bak rather than
      Bax by inactivating Mcl-1 and Bcl-XL.
AB  - Vesicular stomatitis virus (VSV) induces apoptosis via the mitochondrial pathway.
      The mitochondrial pathway is regulated by the Bcl-2 family of proteins, which
      consists of both pro- and antiapoptotic members. To determine the relative
      importance of the multidomain proapoptotic Bcl-2 family members Bak and Bax, HeLa
      cells were transfected with Bak and/or Bax small interfering RNA (siRNA) and
      subsequently infected with recombinant wild-type VSV. Our results showed that Bak
      is more important than Bax for the induction of apoptosis in this system. Bak is
      regulated by two antiapoptotic Bcl-2 proteins, Mcl-1, which is rapidly turned
      over, and Bcl-X(L), which is relatively stable. Inhibition of host gene
      expression by the VSV M protein resulted in the degradation of Mcl-1 but not Bcl
      X(L). However, inactivation of both Mcl-1 and Bcl-X(L) was required for cells to
      undergo apoptosis. While inactivation of Mcl-1 was due to inhibition of its
      expression, inactivation of Bcl-X(L) indicates a role for one or more BH3-only
      Bcl-2 family members. VSV-induced apoptosis was inhibited by transfection with
      siRNA against Bid, a BH3-only protein that is normally activated by the cleavage
      of caspase-8, the initiator caspase associated with the death receptor pathway.
      Similarly, treatment with an inhibitor of caspase-8 inhibited VSV-induced
      apoptosis. These results indicate a role for cross talk from the death receptor
      pathway in the activation of the mitochondrial pathway by VSV.

PMID- 19587034
TI  - The linear plasmid prophage Vp58.5 of Vibrio parahaemolyticus is closely related
      to the integrating phage VHML and constitutes a new incompatibility group of
      telomere phages.
AB  - Vibrio parahaemolyticus O3:K6 pandemic strains recovered in Chile frequently
      possess a 42-kb plasmid which is the prophage of a myovirus. We studied the
      prototype phage VP58.5 and show that it does not integrate into the host cell
      chromosome but replicates as a linear plasmid (Vp58.5) with covalently closed
      ends (telomeres). The Vp58.5 replicon coexists with other plasmid prophages (N15,
      PY54, and PhiKO2) in the same cell and thus belongs to a new incompatibility
      group of telomere phages. We determined the complete nucleotide sequence (42,612
      nucleotides) of the VP58.5 phage DNA and compared it with that of the plasmid
      prophage. The two molecules share the same nucleotide sequence but are 35%
      circularly permuted to each other. In contrast to the hairpin ends of the
      plasmid, VP58.5 phage DNA contains 5'-protruding ends. The VP58.5 sequence is 92%
      identical to the sequence of phage VHML, which was reported to integrate into the
      host chromosome. However, the gene order and termini of the phage DNAs are
      different. The VHML genome exhibits the same gene order as does the Vp58.5
      plasmid. VHML phage DNA has been reported to contain terminal inverted repeats.
      This repetitive sequence is similar to the telomere resolution site (telRL) of
      VP58.5 which, after processing by the phage protelomerase, forms the hairpin ends
      of the Vp58.5 prophage. It is discussed why these closely related phages may be
      so different in terms of their genome ends and their lifestyle.

PMID- 19587036
TI  - Nucleoside monophosphate complex structures of the endonuclease domain from the
      influenza virus polymerase PA subunit reveal the substrate binding site inside
      the catalytic center.
AB  - Highly pathogenic influenza virus strains currently in circulation pose a
      significant risk of a global pandemic. Following the reported crystal structure
      of the endonuclease domain from the avian influenza virus polymerase PA subunit,
      here we report the results of a systematic X-ray crystallographic analysis of its
      complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs).
      Electron density corresponding to the monophosphate moiety of each nucleotide was
      apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site
      was found to contribute to nucleoside binding. The NMP complex structures should
      represent the conformation of the bound product after nuclease cleavage.
      Moreover, one solvent molecule was found to occupy an equivalent position to the
      second reported Mn(2+) ion, where it mediates the interaction between bound NMPs
      and the N-terminal PA domain in the presence of the Mg(2+) ion. The results
      presented here indicate a possible cleavage mechanism and identify a distinct
      nucleotide binding pocket. The identification of this binding pocket opens a new
      avenue for anti-influenza drug discovery, targeting the cap-dependent
      endonuclease, in response to the worldwide threat of influenza.

PMID- 19587035
TI  - Insight into poliovirus genome replication and encapsidation obtained from
      studies of 3B-3C cleavage site mutants.
AB  - A poliovirus (PV) mutant (termed GG), which is incapable of producing 3AB, VPg,
      and 3CD proteins due to a defective cleavage site between the 3B and 3C proteins,
      replicated, producing 3BC-linked RNA rather than the VPg-linked RNA produced by
      the wild type (WT). GG PV RNA is quasi-infectious. The yield of infectious GG PV
      relative to replicated RNA is reduced by almost 5 logs relative to that of WT PV.
      Proteolytic activity required for polyprotein processing is normal for the GG
      mutant. 3BC-linked RNA can be encapsidated as efficiently as VPg-linked RNA.
      However, a step after genome replication but preceding virus assembly that is
      dependent on 3CD and/or 3AB proteins limits production of infectious GG PV. This
      step may involve release of replicated genomes from replication complexes. A
      pseudorevertant (termed EG) partially restored cleavage at the 3B-3C cleavage
      site. The reduced rate of formation of 3AB and 3CD caused corresponding
      reductions in the observed rate of genome replication and infectious virus
      production by EG PV without impacting the final yield of replicated RNA or
      infectious virus relative to that of WT PV. Using EG PV, we showed that genome
      replication and encapsidation were distinct steps in the multiplication cycle.
      Ectopic expression of 3CD protein reversed the genome replication phenotype
      without alleviating the infectious-virus production phenotype. This is the first
      report of a trans-complementable function for 3CD for any picornavirus. This
      observation supports an interaction between 3CD protein and viral and/or host
      factors that is critical for genome replication, perhaps formation of replication
      complexes.

PMID- 19587037
TI  - The porcine reproductive and respiratory syndrome virus nsp2 cysteine protease
      domain possesses both trans- and cis-cleavage activities.
AB  - The N terminus of the replicase nonstructural protein 2 (nsp2) of porcine
      reproductive and respiratory syndrome virus (PRRSV) contains a putative cysteine
      protease domain (PL2). Previously, we demonstrated that deletion of either the
      PL2 core domain (amino acids [aa] 47 to 180) or the immediate downstream region
      (aa 181 to 323) is lethal to the virus. In this study, the PL2 domain was found
      to encode an active enzyme that mediates efficient processing of nsp2-3 in CHO
      cells. The PL2 protease possessed both trans- and cis-cleavage activities, which
      were distinguished by individual point mutations in the protease domain. The
      minimal size required to maintain these two enzymatic activities included nsp2 aa
      47 to 240 (Tyr(47) to Cys(240)) and aa 47 to 323 (Tyr(47) to Leu(323)),
      respectively. Introduction of targeted amino acid mutations in the protease
      domain confirmed the importance of the putative Cys(55)- His(124) catalytic motif
      for nsp2/3 proteolysis in vitro, as were three additional conserved cysteine
      residues (Cys(111), Cys(142), and Cys(147)). The conserved aspartic acids (e.g.,
      Asp(89)) were essential for the PL2 protease trans-cleavage activity. Reverse
      genetics revealed that the PL2 trans-cleavage activity played an important role
      in the PRRSV replication cycle in that mutations that impaired the PL2 protease
      trans function, but not the cis activity, were detrimental to viral viability.
      Lastly, the potential nsp2/3 cleavage site was probed. Mutations with the largest
      impact on in vitro cleavage were at or near the G(1196)|G(1197) dipeptide.

PMID- 19587038
TI  - Clearance of measles virus from persistently infected cells by short hairpin RNA.
AB  - Subacute sclerosing panencephalitis (SSPE) is a demyelinating central nervous
      system disease caused by a persistent measles virus (MV) infection of neurons and
      glial cells. There is still no specific therapy available, and in spite of an
      intact innate and adaptive immune response, SSPE leads inevitably to death. In
      order to select effective antiviral short interfering RNAs (siRNAs), we
      established a plasmid-based test system expressing the mRNA of DsRed2 fused with
      mRNA sequences of single viral genes, to which certain siRNAs were directed.
      siRNA sequences were expressed as short hairpin RNA (shRNA) from a lentiviral
      vector additionally expressing enhanced green fluorescent protein (EGFP) as an
      indicator. Evaluation by flow cytometry of the dual-color system (DsRed and EGFP)
      allowed us to find optimal shRNA sequences. Using the most active shRNA
      constructs, we transduced persistently infected human NT2 cells expressing virus
      encoded HcRed (piNT2-HcRed) as an indicator of infection. shRNA against N, P, and
      L mRNAs of MV led to a reduction of the infection below detectable levels in a
      high percentage of transduced piNT2-HcRed cells within 1 week. The fraction of
      virus-negative cells in these cultures was constant over at least 3 weeks
      posttransduction in the presence of a fusion-inhibiting peptide (Z-Phe-Phe-Gly),
      preventing the cell fusion of potentially cured cells with persistently infected
      cells. Transduced piNT2 cells that lost HcRed did not fuse with underlying
      Vero/hSLAM cells, indicating that these cells do not express viral proteins any
      more and are "cured." This demonstrates in tissue culture that NT2 cells
      persistently infected with MV can be cured by the transduction of lentiviral
      vectors mediating the long-lasting expression of anti-MV shRNA.

PMID- 19587040
TI  - A one-plasmid system to generate influenza virus in cultured chicken cells for
      potential use in influenza vaccine.
AB  - Influenza virus has a set of ribonucleoproteins (RNPs) consisting of viral RNAs,
      influenza virus polymerase subunits, and nucleoprotein. Intracellular
      reconstitution of the whole set of RNPs via plasmid transfection results in the
      generation of influenza virus. By the use of reverse genetics and dual promoters,
      we constructed a 23.6-kb eight-unit plasmid that contains all the required
      constituents to generate influenza virus in chicken cells. Our "one-plasmid"
      system generated higher titers of influenza virus in chicken cells than the
      "eight-plasmid" system, enabling a simpler approach for generating vaccine seeds.
      Our study identified plasmid size as a potential limiting factor affecting
      transfection efficiency and hence the influenza viral yield from chicken cells.

PMID- 19587039
TI  - A 49-kilodalton isoform of the adenovirus type 5 early region 1B 55-kilodalton
      protein is sufficient to support virus replication.
AB  - The adenovirus type 5 (Ad5) early region 1B 55-kDa (E1B-55K) protein is a
      multifunctional regulator of cell-cycle-independent virus replication that
      participates in many processes required for maximal virus production. As part of
      a study of E1B-55K function, we generated the Ad5 mutant H5pm4133, carrying stop
      codons after the second and seventh codons of the E1B reading frame, thereby
      eliminating synthesis of the full-length 55K product and its smaller derivatives.
      Unexpectedly, phenotypic studies revealed that H5pm4133 fully exhibits the
      characteristics of wild-type (wt) Ad5 in all assays tested. Immunoblot analyses
      demonstrated that H5pm4133 and wt Ad5 produce very low levels of two distinct
      polypeptides in the 48- to 49-kDa range, which lack the amino-terminal region but
      contain segments from the central and carboxy-terminal part of the 55K protein.
      Genetic and biochemical studies with different Ad5 mutants show that at least one
      of these isoforms consists of two closely migrating polypeptides of 433 amino
      acid residues (433R) and 422R, which are produced by translation initiation at
      two downstream AUG codons of the 55K reading frame. Significantly, a virus mutant
      producing low levels of the 433R isoform alone replicated to levels comparable to
      those of wt Ad5, demonstrating that this polypeptide provides essentially all
      functions of E1B-55K required to promote maximal virus growth in human tumor
      cells. Altogether, these results extend previous findings that the wt Ad5 E1B
      region encodes a series of smaller isoforms of E1B-55K and demonstrate that very
      low levels of at least one of these novel proteins (E1B-433R) are sufficient for
      a productive infection.

PMID- 19587041
TI  - Mouse norovirus replication is associated with virus-induced vesicle clusters
      originating from membranes derived from the secretory pathway.
AB  - Human noroviruses (family Caliciviridae) are the leading cause of nonbacterial
      gastroenteritis worldwide. Despite the prevalence of these viruses within the
      community, the study of human norovirus has largely been hindered due to the
      inability to cultivate the viruses ex vivo and the lack of a small-animal model.
      In 2003, the discovery of a novel murine norovirus (MNV-1) and the identification
      of the tropism of MNV-1 for cells of a mononuclear origin led to the
      establishment of the first norovirus tissue culture system. Like other positive
      sense RNA viruses, MNV-1 replication is associated with host membranes, which
      undergo significant rearrangement during infection. We characterize here the
      subcellular localization of the MNV-1 open reading frame 1 proteins and viral
      double-stranded RNA (dsRNA). Over the course of infection, dsRNA and the MNV-1
      RNA-dependent RNA polymerase (NS7) were observed to proliferate from punctate
      foci located in the perinuclear region. All of the MNV-1 open reading frame 1
      proteins were observed to colocalize with dsRNA during the course of infection.
      The MNV-1 replication complex was immunolocalized to virus-induced vesicle
      clusters formed in the cytoplasm of infected cells. Both dsRNA and MNV-1 NS7 were
      observed to localize to the limiting membrane of the individual clusters by cryo
      immunoelectron microscopy. We show that the MNV-1 replication complex initially
      associates with membranes derived from the endoplasmic reticulum, trans-Golgi
      apparatus, and endosomes. In addition, we show that MNV-1 replication is
      insensitive to the fungal metabolite brefeldin A and consistently does not appear
      to recruit coatomer protein complex I (COPI) or COPII component proteins during
      replication. These data provide preliminary insights into key aspects of
      replication of MNV-1, which will potentially further our understanding of the
      pathogenesis of noroviruses and aid in the identification of potential targets
      for drug development.

PMID- 19587042
TI  - Naturally occurring hepatitis C virus subgenomic deletion mutants replicate
      efficiently in Huh-7 cells and are trans-packaged in vitro to generate infectious
      defective particles.
AB  - Naturally occurring hepatitis C virus (HCV) subgenomic RNAs have been found in
      several HCV patients. These subgenomic deletion mutants, mostly lacking the genes
      encoding envelope glycoproteins, were found in both liver and serum, where their
      relatively high abundance suggests that they are capable of autonomous
      replication and can be packaged and secreted in viral particles, presumably
      harboring the envelope proteins from wild type virus coinfecting the same cell.
      We recapitulated some of these natural subgenomic deletions in the context of the
      isolate JFH-1 and confirmed these hypotheses in vitro. In Huh-7.5 cells, these
      deletion-containing genomes show robust replication and can be efficiently trans
      packaged and infect naive Huh-7.5 cells when cotransfected with the full-length
      wild-type J6/JFH genome. The genome structure of these natural subgenomic
      deletion mutants was dissected, and the maintenance of both core and NS2 regions
      was proven to be significant for efficient replication and trans-packaging. To
      further explore the requirements needed to achieve trans-complementation, we
      provided different combinations of structural proteins in trans. Optimal trans
      complementation was obtained when fragments of the polyprotein encompassing core
      to p7 or E1 to NS2 were expressed. Finally, we generated a stable helper cell
      line, constitutively expressing the structural proteins from core to p7, which
      efficiently supports trans-complementation of a subgenomic deletion encompassing
      amino acids 284 to 732. This cell line can produce and be infected by defective
      particles, thus representing a powerful tool to investigate the life cycle and
      relevance of natural HCV subgenomic deletion mutants in vivo.

PMID- 19587043
TI  - Influenza virus directly infects human natural killer cells and induces cell
      apoptosis.
AB  - Influenza is an acute respiratory viral disease that is transmitted in the first
      few days of infection. Evasion of host innate immune defenses, including natural
      killer (NK) cells, is important for the virus's success as a pathogen of humans
      and other animals. NK cells encounter influenza viruses within the
      microenvironment of infected cells and are important for host innate immunity
      during influenza virus infection. It is therefore important to investigate the
      direct effects of influenza virus on NK cells. In this study, we demonstrated for
      the first time that influenza virus directly infects and replicates in primary
      human NK cells. Viral entry into NK cells was mediated by both clathrin- and
      caveolin-dependent endocytosis rather than through macropinocytosis and was
      dependent on the sialic acids on cell surfaces. In addition, influenza virus
      infection induced a marked apoptosis of NK cells. Our findings suggest that
      influenza virus can directly target and kill NK cells, a potential novel strategy
      of influenza virus to evade the NK cell innate immune defense that is likely to
      facilitate viral transmission and may also contribute to virus pathogenesis.

PMID- 19587044
TI  - The immune adaptor molecule SARM modulates tumor necrosis factor alpha production
      and microglia activation in the brainstem and restricts West Nile Virus
      pathogenesis.
AB  - Sterile alpha and HEAT/Armadillo motif (SARM) is a highly conserved
      Toll/interleukin-1 receptor (TIR)-containing adaptor protein that is believed to
      negatively regulate signaling of the pathogen recognition receptors Toll-like
      receptor 3 (TLR3) and TLR4. To test its physiological function in the context of
      a microbial infection, we generated SARM(-/-) mice and evaluated the impact of
      this deficiency on the pathogenesis of West Nile virus (WNV), a neurotropic
      flavivirus that requires TLR signaling to restrict infection. Although SARM was
      preferentially expressed in cells of the central nervous system (CNS), studies
      with primary macrophages, neurons, or astrocytes showed no difference in viral
      growth kinetics. In contrast, viral replication was increased specifically in the
      brainstem of SARM(-/-) mice, and this was associated with enhanced mortality
      after inoculation with a virulent WNV strain. A deficiency of SARM was also
      linked to reduced levels of tumor necrosis factor alpha (TNF-alpha), decreased
      microglia activation, and increased neuronal death in the brainstem after WNV
      infection. Thus, SARM appears to be unique among the TIR adaptor molecules, since
      it functions to restrict viral infection and neuronal injury in a brain region
      specific manner, possibly by modulating the activation of resident CNS
      inflammatory cells.

PMID- 19587045
TI  - Impact of cytotoxic-T-lymphocyte memory induction without virus-specific CD4+ T
      Cell help on control of a simian immunodeficiency virus challenge in rhesus
      macaques.
AB  - Despite many efforts to develop AIDS vaccines eliciting virus-specific T-cell
      responses, whether induction of these memory T cells by vaccination before human
      immunodeficiency virus (HIV) exposure can actually contribute to effective T-cell
      responses postinfection remains unclear. In particular, induction of HIV-specific
      memory CD4(+) T cells may increase the target cell pool for HIV infection because
      the virus preferentially infects HIV-specific CD4(+) T cells. However, virus
      specific CD4(+) helper T-cell responses are thought to be important for
      functional CD8(+) cytotoxic-T-lymphocyte (CTL) induction in HIV infection, and it
      has remained unknown whether HIV-specific memory CD8(+) T cells induced by
      vaccination without HIV-specific CD4(+) T-cell help can exert effective responses
      after virus exposure. Here we show the impact of CD8(+) T-cell memory induction
      without virus-specific CD4(+) T-cell help on the control of a simian
      immunodeficiency virus (SIV) challenge in rhesus macaques. We developed a
      prophylactic vaccine by using a Sendai virus (SeV) vector expressing a single SIV
      Gag(241-249) CTL epitope fused with enhanced green fluorescent protein (EGFP).
      Vaccination resulted in induction of SeV-EGFP-specific CD4(+) T-cell and Gag(241
      249)-specific CD8(+) T-cell responses. After a SIV challenge, the vaccinees
      showed dominant Gag(241-249)-specific CD8(+) T-cell responses with higher
      effector memory frequencies in the acute phase and exhibited significantly
      reduced viral loads. These results demonstrate that virus-specific memory CD8(+)
      T cells induced by vaccination without virus-specific CD4(+) T-cell help could
      indeed facilitate SIV control after virus exposure, indicating the benefit of
      prophylactic vaccination eliciting virus-specific CTL memory with non-virus
      specific CD4(+) T-cell responses for HIV control.

PMID- 19587046
TI  - Increased eIF2alpha phosphorylation attenuates replication of herpes simplex
      virus 2 vhs mutants in mouse embryonic fibroblasts and correlates with reduced
      accumulation of the PKR antagonist ICP34.5.
AB  - Herpes simplex virus 2 (HSV-2) strains containing mutations in the virion host
      shutoff (vhs) protein are attenuated for replication compared with wild-type
      virus in mouse embryonic fibroblasts (MEFs). However, HSV-2 vhs mutants replicate
      to near wild-type levels in the absence of the RNA-activated protein kinase
      (PKR). PKR is one of several kinases that phosphorylates the eukaryotic
      initiation factor 2alpha (eIF2alpha) to inhibit translation initiation, and we
      previously found that more of the phosphorylated form of eIF2alpha accumulates in
      MEFs infected with HSV-2 vhs mutants than with wild-type virus. Here, we show
      that this increase in phosphorylated eIF2alpha is primarily PKR dependent. Using
      MEFs expressing nonphosphorylatable eIF2alpha, we demonstrate that phosphorylated
      eIF2alpha is the primary cause of attenuated replication of HSV-2 vhs mutants and
      that attenuation correlates with decreased accumulation of viral proteins.
      Normally, HSV antagonizes eIF2alpha phosphorylation through the action of
      ICP34.5, which redirects protein phosphatase 1alpha (PP1alpha) to dephosphorylate
      eIF2alpha during infection. We show that ICP34.5 does not accumulate efficiently
      in MEFs infected with HSV-2 vhs mutant viruses, suggesting that the accumulation
      of phosphorylated eIF2alpha and the attenuated phenotype of HSV-2 vhs mutants in
      MEFs result from a deficiency in ICP34.5.

PMID- 19587047
TI  - CXCR3 deficiency increases susceptibility to genital herpes simplex virus type 2
      infection: Uncoupling of CD8+ T-cell effector function but not migration.
AB  - CXCR3 is a G-protein-coupled receptor preferentially expressed by activated T
      cells, NK cells, and dendritic cells. Signaling through gamma interferon
      regulated chemokines CXCL9, CXCL10, CXCL11, and CXCR3 plays a critical role in
      the immune response of many viral pathogens. However, the relevance of CXCR3 for
      optimal T-cell activation and the induction of regulatory transcription factors
      (i.e., T-bet and eomesodermin) relative to host immune defense against genital
      herpes simplex virus type 2 (HSV-2) infection have been poorly defined. In this
      study, we evaluated the requirement of CXCR3 expression during genital HSV-2
      infection using mice deficient in CXCR3 (CXCR3(-/-)) along with wild-type (WT)
      controls, assessing the resistance of mice to viral infection and focusing on the
      cytokine/chemokine response, phenotypic analysis of recruited leukocytes, and
      functional analysis of CD8(+) T cells. CXCR3(-/-) mice showed a heightened
      sensitivity to infection compared to WT animals in terms of the viral burden in
      infected tissues as well as elevated mortality. The poor response of CXCR3(-/-)
      mice to viral infection was associated with reduced cytotoxic T-lymphocyte
      activity through the impairment of T-bet, perforin, and granzyme B expression by
      CD8(+) T cells. Corresponding with the defective cytolytic activity, a reduction
      in recruitment of plasmacytoid dendritic cells and CD80 expression in CD11c(+)
      dendritic cells in the draining lymph nodes of CXCR3(-/-) mice were detected.
      Collectively, the results provide a new perspective to CXCR3 signaling for the
      appropriate activation of CD8(+) T cells required for host defense against
      genital HSV-2 infection.

PMID- 19587048
TI  - Protein kinase G phosphorylates mosquito-borne flavivirus NS5.
AB  - Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is a
      conserved feature of flaviviruses, but the kinase(s) responsible and function(s)
      remain unknown. Mass spectrometry was used to compare the phosphorylation sites
      of the NS5 proteins of yellow fever virus (YFV) and dengue virus (DENV), two
      flaviviruses transmitted by mosquitoes. Seven DENV phosphopeptides were
      identified, but only one conserved phosphoacceptor site (threonine 449 in DENV)
      was identified in both viruses. This site is predicted to be a protein kinase G
      (PKG) recognition site and is a strictly conserved serine/threonine
      phosphoacceptor site in mosquito-borne flaviviruses. In contrast, in tick-borne
      flaviviruses, this residue is typically a histidine. A DENV replicon engineered
      to have the tick-specific histidine residue at this position is replication
      defective. We show that DENV NS5 purified from Escherichia coli is a substrate
      for PKG in vitro and facilitates the autophosphorylation of PKG as seen with
      cellular substrates. Phosphorylation in vitro by PKG also occurs at threonine
      449. Activators and inhibitors of PKG modulate DENV replication in cell culture
      but not replication of the tick-borne langat virus. Collectively, these data
      argue that PKG mediates a conserved serine/threonine phosphorylation event
      specifically for flaviviruses spread by mosquitoes.

PMID- 19587049
TI  - Host shutoff is a conserved phenotype of gammaherpesvirus infection and is
      orchestrated exclusively from the cytoplasm.
AB  - Lytic infection with the two human gammaherpesviruses, Kaposi's sarcoma
      associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), leads to significant
      depletion of the cellular transcriptome. This host shutoff phenotype is driven by
      the conserved herpesviral alkaline exonuclease, termed SOX in KSHV and BGLF5 in
      EBV, which in gammaherpesviruses has evolved the genetically separable ability to
      target cellular mRNA. We now show that host shutoff is also a prominent
      consequence of murine gammaherpesvirus 68 (MHV68) infection, which is widely used
      as a model system to study pathogenesis of these viruses in vivo. The effector of
      MHV68-induced host shutoff is its SOX homolog, here termed muSOX. There is
      remarkable functional conservation of muSOX host shutoff activities with those of
      KSHV SOX, including the recently described ability of SOX to induce mRNA
      hyperadenylation in the nucleus as well as cause nuclear relocalization of the
      poly(A) binding protein. SOX and muSOX localize to both the nucleus and cytoplasm
      of infected cells. Using spatially restricted variants of these proteins, we go
      on to demonstrate that all known host shutoff-related activities of SOX and muSOX
      are orchestrated exclusively from the cytoplasm. These results have important
      mechanistic implications for how SOX and muSOX target nascent cellular
      transcripts in the nucleus. Furthermore, our findings establish MHV68 as a new,
      genetically tractable model to study host shutoff.

PMID- 19587050
TI  - Transcriptional changes in the brains of cattle orally infected with the bovine
      spongiform encephalopathy agent precede detection of infectivity.
AB  - Bovine spongiform encephalopathy (BSE) is a fatal, transmissible,
      neurodegenerative disease of cattle. BSE can be transmitted experimentally
      between cattle through the oral route, and in this study, brain tissue samples
      from animals at different time points postinoculation were analyzed for changes
      in gene expression. The aims of this study were to identify differentially
      regulated genes during the progression of BSE using microarray-based gene
      expression profiling and to understand the effect of prion pathogenesis on gene
      expression. A total of 114 genes were found to be differentially regulated over
      the time course of the infection, and many of these 114 genes encode proteins
      involved in immune response, apoptosis, cell adhesion, stress response, and
      transcription. This study also revealed a broad correlation between gene
      expression profiles and the progression of BSE in cattle. At 21 months
      postinoculation, the largest number of differentially regulated genes was
      detected, suggesting that there are many pathogenic processes in the animal brain
      even prior to the detection of infectivity in the central nervous systems of
      these orally infected cattle. Moreover, evidence is presented to suggest that it
      is possible to predict the infectious status of animals using the expression
      profiles from this study.

PMID- 19587051
TI  - Ebolavirus glycoprotein GP masks both its own epitopes and the presence of
      cellular surface proteins.
AB  - Ebolavirus (EBOV) is the etiological agent of a severe hemorrhagic fever with a
      high mortality rate. The spike glycoprotein (GP) is believed to be one of the
      major determinants of virus pathogenicity. In this study, we demonstrated the
      molecular mechanism responsible for the downregulation of surface markers caused
      by EBOV GP expression. We showed that expression of mature GP on the plasma
      membrane results in the masking of cellular surface proteins, including major
      histocompatibility complex class I. Overexpression of GP also results in the
      masking of certain antigenic epitopes on GP itself, causing an illusory effect of
      disappearance from the plasma membrane.

PMID- 19587053
TI  - Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus
      infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells.
AB  - A number of emerging molecules and pathways have been implicated in mediating the
      T-cell exhaustion characteristic of chronic viral infection. Not all
      dysfunctional T cells express PD-1, nor are they all rescued by blockade of the
      PD-1/PD-1 ligand pathway. In this study, we characterize the expression of T-cell
      immunoglobulin and mucin domain-containing protein 3 (Tim-3) in chronic hepatitis
      C infection. For the first time, we found that Tim-3 expression is increased on
      CD4(+) and CD8(+) T cells in chronic hepatitis C virus (HCV) infection. The
      proportion of dually PD-1/Tim-3-expressing cells is greatest in liver-resident T
      cells, significantly more so in HCV-specific than in cytomegalovirus-specific
      cytotoxic T lymphocytes. Tim-3 expression correlates with a dysfunctional and
      senescent phenotype (CD127(low) CD57(high)), a central rather than effector
      memory profile (CD45RA(negative) CCR7(high)), and reduced Th1/Tc1 cytokine
      production. We also demonstrate the ability to enhance T-cell proliferation and
      gamma interferon production in response to HCV-specific antigens by blocking the
      Tim-3-Tim-3 ligand interaction. These findings have implications for the
      development of novel immunotherapeutic approaches to this common viral infection.

PMID- 19587052
TI  - Dynamic host energetics and cytoskeletal proteomes in human immunodeficiency
      virus type 1-infected human primary CD4 cells: analysis by multiplexed label-free
      mass spectrometry.
AB  - We report on a proteomic analysis of ex vivo human immunodeficiency virus (HIV)
      type 1 infection in human primary CD4 cells by shotgun liquid chromatography
      tandem mass spectrometry analysis, revealing two distinct proteomic profiles at
      two phases of virus replication. Relative to mock-infected cells, 168 signature
      proteins exhibited abundance changes at the first sign of Gag p24 production (8 h
      postinfection [p.i.]) or the peak of virus replication (24 h p.i.);
      interestingly, most of the changes were exclusive to only one phase of virus
      replication. Based on characterization by functional ontology and known human-HIV
      protein interactions, we observed the enrichment for protein abundance increases
      pertaining to protein synthesis and nucleasomal reorganization amid an otherwise
      placid cellular proteome at the first sign of HIV replication. In contrast, we
      observed indications of decreased protein turnover, concomitant with heightened
      DNA repair activities and preludes to apoptosis, in the presence of robust virus
      replication. We also observed hints of disruptions in protein and small molecule
      trafficking. Our label-free proteomic strategy allowed us to perform multiplexed
      comparisons-we buttressed our detection specificity with the use of a reverse
      transcriptase inhibitor as a counterscreen, enabling highlighting of cellular
      protein abundance changes unique to robust virus replication as opposed to viral
      entry. In conjunction with complementary high-throughput screens for cellular
      partners of HIV, we put forth a model pinpointing specific rerouting of cellular
      biosynthetic, energetic, and trafficking pathways as HIV replication accelerates
      in human primary CD4 cells.

PMID- 19587054
TI  - The impact of individual human immunodeficiency virus type 1 protease mutations
      on drug susceptibility is highly influenced by complex interactions with the
      background protease sequence.
AB  - The requirement for multiple mutations for protease inhibitor (PI) resistance
      necessitates a better understanding of the molecular basis of resistance
      development. The novel bioinformatics resistance determination approach presented
      here elaborates on genetic profiles observed in clinical human immunodeficiency
      virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild
      type HIV-1 background to generate a large number of close variants, covering 69
      mutation clusters between multi-PI-resistant viruses and their corresponding
      genetically closely related, but PI-susceptible, counterparts. The vast number of
      mutants generated facilitates a profound and broad analysis of the influence of
      the background on the effect of individual PI resistance-associated mutations (PI
      RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed
      between susceptible and resistant viruses were varied while maintaining the
      background sequence from the resistant virus. The PI darunavir was used to
      evaluate PI susceptibility. Single sets allowed delineation of the impact of
      individual mutations on PI susceptibility, as well as the influence of PI-RAMs on
      one another. Comparing across sets, it could be inferred how the background
      influenced the interaction between two mutations, in some cases even changing
      antagonistic relationships into synergistic ones or vice versa. The approach
      elaborates on patient data and demonstrates how the specific mutational
      background greatly influences the impact of individual mutations on PI
      susceptibility in clinical patterns.

PMID- 19587055
TI  - Human immunodeficiency virus type 1 nucleocapsid inhibitors impede trans
      infection in cellular and explant models and protect nonhuman primates from
      infection.
AB  - Here, we report that the S-acyl-2-mercaptobenzamide thioester (SAMT) class of
      human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7)
      inhibitors was able to prevent transmission of HIV-1 from infected cells,
      including primary cells. Furthermore, when SAMTs were introduced during an HIV-1
      challenge of cervical explant tissue, inhibition of dissemination of infectious
      virus by cells emigrating from the tissue explants was observed. Preliminary
      studies using a rhesus macaque vaginal challenge model with mixed R5 and X4
      simian-human immunodeficiency virus infection found that five of six monkeys were
      completely protected, with the remaining animal being partially protected,
      infected only by the R5 virus. These data suggest that SAMTs may be promising new
      drug candidates for further development in anti-HIV-1 topical microbicide
      applications.

PMID- 19587056
TI  - Differential incorporation of cholesterol by Sindbis virus grown in mammalian or
      insect cells.
AB  - Cholesterol has been shown to be essential for the fusion of alphaviruses with
      artificial membranes (liposomes). Cholesterol has also been implicated as playing
      an essential and critical role in the processes of entry and egress of
      alphaviruses in living cells. Paradoxically, insects, the alternate host for
      alphaviruses, are cholesterol auxotrophs and contain very low levels of this
      sterol. To further evaluate the role of cholesterol in the life cycle of
      alphaviruses, the cholesterol levels of the alphavirus Sindbis produced from
      three different mosquito (Aedes albopictus) cell lines; one other insect cell
      line, Sf21 from Spodoptera frugiperda; and BHK (mammalian) cells were measured.
      Sindbis virus was grown in insect cells under normal culture conditions and in
      cells depleted of cholesterol by growth in serum delipidated by using Cab-O-sil,
      medium treated with methyl-beta-cyclodextrin, or serum-free medium. The levels of
      cholesterol incorporated into the membranes of the cells and into the virus
      produced from these cells were determined. Virus produced from these treated and
      untreated cells was compared to virus grown in BHK cells under standard
      conditions. The ability of insect cells to produce Sindbis virus after
      delipidation was found to be highly cell specific and not dependent on the level
      of cholesterol in the cell membrane. A very low level of cholesterol was required
      for the generation of wild-type levels of infectious Sindbis virus from
      delipidated cells. The data show that one role of the virus membrane is
      structural, providing the stability required for infectivity that may not be
      provided by the delipidated membranes in some cells. These data show that the
      amount of cholesterol in the host cell membrane in and of itself has no effect on
      the process of virus assembly or on the ability of virus to infect cells. Rather,
      these data suggest that the cholesterol dependence reported for infectivity and
      assembly of Sindbis virus is a reflection of differences in the insect cell lines
      used and the methods of delipidation.

PMID- 19587057
TI  - Defining APOBEC3 expression patterns in human tissues and hematopoietic cell
      subsets.
AB  - Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or
      mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we
      report a detailed examination of human APOBEC3 gene expression, focusing on
      APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human
      immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif.
      A3G and A3F are expressed widely in hematopoietic cell populations, including T
      cells, B cells, and myeloid cells, as well as in tissues where mRNA levels
      broadly correlate with the lymphoid cell content (gonadal tissues are
      exceptions). By measuring mRNA copy numbers, we find that A3G mRNA is
      approximately 10-fold more abundant than A3F mRNA, implying that A3G is the more
      significant anti-HIV-1 factor in vivo. A3G and A3F levels also vary between
      donors, and these differences are sustained over 12 months. Responses to T-cell
      activation or cytokines reveal that A3G and A3F mRNA levels are induced
      approximately 10-fold in macrophages and dendritic cells (DCs) by alpha
      interferon (IFN-alpha) and approximately 4-fold in naive CD4(+) T cells. However,
      immunoblotting revealed that A3G protein levels are induced by IFN-alpha in
      macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN
      gamma had a minimal impact on A3G or A3F expression. Finally, we noted that A3A
      mRNA expression and protein expression are exquisitely sensitive to IFN-alpha
      induction in CD4(+) T cells, macrophages, and DCs but not to T-cell activation or
      other cytokines. Given that A3A does not affect HIV-1 infection, these
      observations imply that this protein may participate in early antiviral innate
      immune responses.

PMID- 19587058
TI  - Two small RNAs encoded within the first 1.5 kilobases of the herpes simplex virus
      type 1 latency-associated transcript can inhibit productive infection and
      cooperate to inhibit apoptosis.
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is
      abundantly expressed in latently infected trigeminal ganglionic sensory neurons.
      Expression of the first 1.5 kb of LAT coding sequences is sufficient for the wild
      type reactivation phenotype in small animal models of infection. The ability of
      the first 1.5 kb of LAT coding sequences to inhibit apoptosis is important for
      the latency-reactivation cycle. Several studies have also concluded that LAT
      inhibits productive infection. To date, a functional LAT protein has not been
      identified, suggesting that LAT is a regulatory RNA. Two small RNAs (sRNAs) were
      previously identified within the first 1.5 kb of LAT coding sequences. In this
      study, we demonstrated that both LAT sRNAs were expressed in the trigeminal
      ganglia of mice latently infected with an HSV-1 strain that expresses LAT but not
      when mice were infected with a LAT null mutant. LAT sRNA1 and sRNA2 cooperated to
      inhibit cold shock-induced apoptosis in mouse neuroblastoma cells. LAT sRNA1, but
      not LAT sRNA2, inhibited apoptosis less efficiently than both sRNAs. When rabbit
      skin cells were cotransfected with plasmids that express LAT sRNA1 and HSV-1
      genomic DNA, the amount of infectious virus released was reduced approximately 3
      logs. Although LAT sRNA2 was less effective at inhibiting virus production, it
      inhibited expression of infected cell protein 4 (ICP4). Neither LAT sRNA had an
      obvious effect on ICP0 expression. These studies suggested that expression of two
      LAT sRNAs plays a role in the latency-reactivation cycle by inhibiting apoptosis
      and productive infection.

PMID- 19587060
TI  - Modification and reorganization of the cytoprotective cellular chaperone Hsp27
      during herpes simplex virus type 1 infection.
AB  - Chaperone-enriched domains are formed in the nuclei of cells lytically infected
      with herpes simplex virus type 1 (HSV-1). These domains, called VICE, for virus
      induced chaperone enriched, contain Hsc70, Hsp70, Hsp40, Hsp90, polyubiquitinated
      proteins, and components of the proteasome machinery. Accumulating evidence
      indicates that these sites may be utilized during infection to sequester
      misfolded, modified, or otherwise unwanted proteins away from viral replication
      compartments, sites of robust transcription, DNA synthesis, and capsid
      maturation. To further explore the role of cellular chaperones and VICE domains
      during HSV-1 infection, we have analyzed the cytoprotective chaperone Hsp27. Here
      we present evidence that Hsp27, which is known to possess several antioxidant
      functions, is rapidly reorganized and modified at early stages in response to HSV
      1 infection and signaling from the mitogen-activated protein kinase p38.
      Immunofluorescence analysis and fractionation experiments reveal disparate
      subcellular localizations of nonphosphorylated and phosphorylated forms of Hsp27
      during wild-type HSV-1 infection. Unmodified forms of Hsp27 are localized in
      nuclear foci that are outside of replication compartments, adjacent to VICE
      domains, and in the cytoplasm. Conversely, we find that phosphorylated forms of
      Hsp27 are localized exclusively in the cytoplasm. Last, in cells depleted of all
      forms of Hsp27, virus replication is significantly reduced.

PMID- 19587061
TI  - The way the dioecious plant Actinidia deliciosa attracts bees: critical role of
      volatile terpenes released from kiwifruit flowers of both genotypes.

PMID- 19587059
TI  - The closest relatives of icosahedral viruses of thermophilic bacteria are among
      viruses and plasmids of the halophilic archaea.
AB  - We have sequenced the genome and identified the structural proteins and lipids of
      the novel membrane-containing, icosahedral virus P23-77 of Thermus thermophilus.
      P23-77 has an approximately 17-kb circular double-stranded DNA genome, which was
      annotated to contain 37 putative genes. Virions were subjected to dissociation
      analysis, and five protein species were shown to associate with the internal
      viral membrane, while three were constituents of the protein capsid. Analysis of
      the bacteriophage genome revealed it to be evolutionarily related to another
      Thermus phage (IN93), archaeal Halobacterium plasmid (pHH205), a genetic element
      integrated into Haloarcula genome (designated here as IHP for integrated
      Haloarcula provirus), and the Haloarcula virus SH1. These genetic elements share
      two major capsid proteins and a putative packaging ATPase. The ATPase is similar
      with the ATPases found in the PRD1-type viruses, thus providing an evolutionary
      link to these viruses and furthering our knowledge on the origin of viruses.

PMID- 19587062
TI  - Variations in Thebesian valve anatomy and coronary sinus ostium: implications for
      invasive electrophysiology procedures.
AB  - AIMS: The coronary sinus (CS) is a commonly cannulated structure in patients
      undergoing electrophysiology studies, catheter ablation of arrhythmias,
      implantation of resynchronization therapy devices and, more recently,
      percutaneous mitral valve repair. The advent of these procedures has led to a
      renewed interest in the anatomy of the coronary venous system including its
      various components. To improve our understanding of this structure, we studied
      the anatomy of the human CS, including the valve that guards its ostium, the
      Thebesian valve. METHODS AND RESULTS: In 75 randomly selected autopsied human
      hearts, we measured the transverse and craniocaudal dimensions of the CS ostium
      and characterized the shape, composition, per cent coverage, and attachment
      points of the Thebesian valve when present. Of the 75 hearts examined, 54 had
      organic heart disease including atherosclerotic coronary artery disease, left
      ventricular hypertrophy, dilated cardiomyopathy, rheumatic heart disease,
      infective endocarditis, and non-rheumatic valvular heart disease. A wide variety
      of Thebesian valve morphologies were seen, ranging from the absence of any valve
      to those where the valve was completely occluding the CS ostium. A Thebesian
      valve was present in the majority of the hearts examined (55/75 hearts-73%). The
      average transverse dimension of the CS ostium in hearts with Thebesian valves
      (7.3+/-2.8 mm) was significantly shorter than those without Thebesian valves
      (9.4+/-2.9 mm, P=0.005). Similarly, the average craniocaudal dimension of the CS
      ostium in hearts with Thebesian valves (7.9+/-2.7 mm) was also significantly
      shorter than those without Thebesian valves (9.3+/-2.9 mm, P=0.045). CONCLUSION:
      Our study shows that some form of Thebesian valve is present in the majority of
      hearts (>70%). Of these, a significant minority (16%) had a valve morphology
      (covering >75% of the ostium, a fibrous, fibromuscular, or muscular composition,
      and devoid of fenestrations) that makes them a 'potentially complicating'
      structure interfering with the cannulation of the CS.

PMID- 19587063
TI  - Radiofrequency ablation of a left appendage focal tachycardia using intracardiac
      ultrasound image integration to guide catheter: minimizing the risk of left
      appendage perforation.

PMID- 19587065
TI  - A new emotional stroop-like task: application to the Down syndrome population.
AB  - The present study proposed to test the applicability of a new emotional Stroop
      like paradigm among 49 adults with Down syndrome (DS), matched with typically
      developing children on gender and receptive vocabulary. Stimuli with neutral and
      emotional content were presented in two identical computerized tasks. This
      experimental design allowed comparisons of inhibition performance according to
      the nature of the material. Main results showed that the DS group processed the
      emotional material more poorly than the control group in the inhibition
      condition, whereas all participants performed near or at ceiling in the control
      condition. Regarding the response latencies, both groups processed emotional
      material slower than the neutral material. The DS participants did not take more
      time to respond than their controls, but they presented a distinct response
      latency pattern during the task: while the control group kept their response
      times constant, the DS group showed an improvement during the task.

PMID- 19587064
TI  - Longer term exposure to secondhand smoke and health outcomes in COPD: impact of
      urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
AB  - INTRODUCTION: Secondhand smoke (SHS) contains respiratory irritants and has the
      potential to adversely affect adults with chronic obstructive pulmonary disease
      (COPD), but few studies have evaluated the impact of SHS on COPD. METHODS: We
      used data from 72 nonsmoking participants in a cohort study of COPD. Urine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was measured as an indicator
      of longer term SHS exposure, whereas urine cotinine was assessed as a measure of
      more recent exposure. The impact of SHS exposure on COPD-related health status
      was examined using multivariate linear regression (controlling for age, sex,
      race, educational attainment, and smoking history). Health status was measured
      using a validated COPD severity score, reported dyspnea, a standard health status
      measure (Short Form-12), and activity restriction. RESULTS: The urine NNAL-to
      creatinine ratio (per interquartile increment) was associated with greater COPD
      severity (mean score increase 1.7 points; 95% CI 0.6-2.8; p = .0003). Higher
      urine NNAL was also related to greater dyspnea, poorer physical health status,
      and more restricted activity (p < or = .05 in all cases). When considered
      simultaneously, longer term exposure (NNAL) had a greater negative impact on COPD
      status than shorter term exposure (cotinine). DISCUSSION: Urine NNAL can be used
      to estimate longer term SHS exposure and negatively affects a number of health
      outcomes among adults with COPD. Screening for and prevention of SHS exposure
      among persons with COPD may be beneficial.

PMID- 19587066
TI  - The contribution of executive control on verbal-learning impairment in patients
      with Parkinson's disease with dementia and Alzheimer's disease.
AB  - Deficits in learning, memory, and executive functions are common cognitive
      sequelae of Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD);
      however, the pattern of deficits within these populations is distinct.
      Hierarchical regression was used to investigate the contribution of two measures
      with executive function properties (Verbal Fluency and CLOX) on list-learning
      performance (CVLT-II total words learned) in a sample of 25 PDD patients and 25
      matched AD patients. Executive measures were predictive of list learning in the
      PDD group after the contribution of overall cognition and contextual verbal
      learning was accounted for, whereas in the AD group the addition of executive
      measures did not add to prediction of variance in CVLT-II learning. These
      findings suggest that deficits in executive functions play a vital role in
      learning impairments in patients with PDD; however, for AD patients, learning
      difficulties appear relatively independent of executive dysfunction.

PMID- 19587067
TI  - BSAC standardized disc susceptibility testing method (version 8).
AB  - There have been considerable changes to the format of the recommendations since
      the previous version (version 7). The majority of the footnotes to the tables
      have been removed and the notations added to the end column; it is hoped that
      this change will avoid confusion in interpretation. Antibiotics have been
      separated into groups, e.g. beta-lactams, aminoglycosides, etc. Recommendations
      for urinary tract infections (UTIs) have been removed for most agents except for
      those that are administered solely for the treatment of uncomplicated UTIs or
      where there are limited recommendations for specific organisms, e.g.
      trimethoprim. For agents that previously had dual recommendations, systemic
      recommendations remain and the intermediate category can be used for
      interpretation for UTIs because intermediate susceptibility infers that the
      infection may respond as the agent is concentrated at the site of infection. This
      change will also avoid errors in interpretation when an organism is isolated from
      multiple sites, e.g. blood and urine. The changes that have been made to version
      7 are as follows: MIC and zone diameter breakpoints (BPs) for trimethoprim,
      fosfomycin and nitrofurantoin for UTIs (Table 7); MIC and zone diameter
      breakpoints (BPs) for doripenem (Tables 7-9); colistin MIC BPs for Pseudomonas
      spp. (Table 9), co-trimoxazole MIC BPs for Stenotrophomonas maltophilia (Table
      10); staphylococci MIC and zone diameter BPs for clarithromycin, clindamycin,
      erythromycin, quinupristin/dalfopristin, trimethoprim UTI, nitrofurantoin UTI and
      rifampicin (Table 11); Streptococcus pneumoniae MIC and zone diameter BPs for
      azithromycin, clarithromycin, erythromycin, co-trimoxazole, linezolid, rifampicin
      and telithromycin (Table 12); addition of streptomycin recommendations for
      enterococci (Table 13); enterococcal MIC and zone diameter BPs for
      quinupristin/dalfopristin, nitrofurantoin UTI and trimethoprim UTI (Table 13);
      beta-haemolytic streptococci MIC and zone diameter BPs for azithromycin,
      clarithromycin, erythromycin and telithromycin (Table 15); clarithromycin and
      erythromycin MIC and zone diameter BPs for Moraxella catarrhalis (Table 16);
      azithromycin MIC BPs for Neisseria gonorrhoeae (Table 17); chloramphenicol and
      rifampicin MIC BPs for Neisseria meningitidis (Table 18); azithromycin MIC BPs
      for Haemophilus influenzae (Table 19); MIC BPs for metronidazole for Bacteroides
      fragilis, Bacteroides thetaiotaomicron and Clostridium perfringens (Tables 23-25,
      respectively); susceptibility testing of Listeria spp. (Appendix 3); the
      acceptable range for ATCC 25923 to a 10 microg tobramycin disc (Table 26).

PMID- 19587069
TI  - Increasing minority research participation through collaboration with community
      outpatient clinics: the STEP-BD Community Partners Experience.
AB  - BACKGROUND: Minority populations have been under-represented in mental health
      research studies. The systematic treatment enhancement program for bipolar
      disorder developed the Community Partners Program (CPP) to address this issue in
      a large, prospective treatment study of persons with bipolar disorder. PURPOSE:
      The primary goal of CPP was to develop a community-based infrastructure for
      studying bipolar disorder that would enhance the ethnic/racial and socioeconomic
      diversity of participants. METHODS: Selected academic sites partnered with local
      clinics (n = 6 partnerships in five cities). This report describes the
      conceptualization, implementation, and qualitative evaluation of CPP, as well as
      quantitative analysis of clinical and sociodemographic differences between the
      samples recruited at academic versus community sites. RESULTS: Quantitative
      analysis of the 155 participants from the six partnerships revealed enrollment of
      45% from minority populations (vs. 15% in academic sites). Significant
      sociodemographic differences were evident not only between academic and community
      sites, but within minority and non-minority groups across site types. Notably,
      clinical differences were not evident between participants from academic and
      community sites. Review of qualitative data suggests that certain factors around
      implementation of research protocols may enhance community participation.
      CONCLUSIONS: Moving research recruitment and participation into community sites
      was more successful in increasing minority enrollment than efforts to attract
      such individuals to academic sites. Recommendations for creating and maintaining
      academic/community partnerships are given. LIMITATIONS: Several important
      variables were not considered including mood severity, hospitalization, or
      treatment differences. Minority participants were grouped by combining African
      American and Hispanics, which may have obscured subgroup differences. A
      derivation of standard qualitative methods was used in this study.

PMID- 19587070
TI  - Elbow flexion after primary reconstruction in obstetric brachial plexus palsy.
AB  - Fifty-two children (54 upper extremities) with obstetric brachial plexus palsy
      who underwent primary reconstruction for elbow flexion restoration were studied.
      The outcomes were analysed in relation to the type of brachial plexus lesion,
      timing of surgery, and the type of reconstruction. Overall, 42 of 54 extremities
      (78%) achieved good and excellent results (> or =M3+). The average postoperative
      muscle grading for the biceps was 3.7 (SD 0.8), and the average postoperative
      active elbow flexion was 108 degrees (SD 33 degrees ). The average elbow flexion
      contracture was 18 degrees (SD 21 degrees ). The timing of surgery and the type
      of the brachial plexus injury significantly influenced the final outcome. The
      best results were seen in early cases (< or =3 months), where the lateral cord
      was reconstructed from intraplexus donors. In this group, minimal flexion
      contracture deformity was observed. Late reconstruction (> or =7 months) of the
      musculocutaneous nerve resulted in inferior results.

PMID- 19587068
TI  - Getting clinical trial results into practice: design, implementation, and process
      evaluation of the ALLHAT Dissemination Project.
AB  - BACKGROUND: Conventional dissemination of clinical trial results has inconsistent
      impact on physician practices. A more comprehensive plan to influence
      determinants of prescribing practices is warranted. PURPOSE: To report the
      response from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
      Attack Trial to the National Heart, Lung, and Blood Institute's requirement for
      dissemination and evaluation of trials with potential immediate public health
      applicability. METHODS: ALLHAT's dissemination plan had two-components: (1) a
      traditional approach of media coverage, scientific presentation, and publication;
      and (2) a theory-based approach targeting determinants of clinician behavior.
      Strategies included: (1) academic detailing, in which physicians approach
      colleagues regarding blood pressure management, (2) direct patient messages to
      stimulate communication with physicians regarding blood pressure control, (3)
      approaches to formulary systems to use educational and economic incentives for
      evidence-based prescription, and (4) direct professional organization appeals to
      clinicians. RESULTS: One hundred and forty-seven Investigator Educators reported
      1698 presentations to 18,524 clinicians in 41 states and the District of
      Columbia. The pre- and post-test responses of 1709 clinicians in the face-to-face
      meetings indicated significant changes in expectations for positive patient
      outcomes and intention to prescribe diuretics. Information was mailed to 55
      individuals representing 20 professional organizations and to eight formulary
      systems. Direct-to-patient messages were provided to 14 sites that host patient
      newsletters and Web sites such as health plans and insurance companies, 62 print
      mass media outlets, and 12 broadcast media sites. LIMITATIONS: It was not within
      the scope of the project to conduct a randomized trial of the impact of the
      dissemination. However, impact evaluation using quasi-experimental designs is
      ongoing. CONCLUSION: A large multi-method dissemination of clinical trial results
      is feasible. Planning for dissemination efforts, including evaluation research,
      should be considered as a part of the funding and design of the clinical trial
      and should begin early in trial planning.

PMID- 19587071
TI  - Severity scoring in carpal tunnel syndrome helps predict the value of
      conservative therapy.
AB  - A prospective study was performed to assess the outcome of conservative treatment
      of carpal tunnel syndrome and to establish the predictive value of preoperative
      Boston carpal tunnel questionnaire scores. Sixty-seven patients with 101
      symptomatic hands underwent an evidence-based education and conservative therapy
      regime prior to surgery. All patients were scored using the Boston carpal tunnel
      questionnaire at presentation and at 3 months. Fifty-eight of 67 patients
      completed both assessments providing a complete assessment of 89 symptomatic
      hands. The mean Boston carpal tunnel questionnaire scores improved significantly
      from 2.45 to 2.12 and throughout the duration of the study 73% of patients
      improved with conservative treatment and 14% did not require surgery. Severity
      scoring at presentation was predictive of outcome with conservative therapy. This
      work suggests that the Boston carpal tunnel questionnaire can be used to identify
      patients who are likely to respond to conservative treatment.

PMID- 19587072
TI  - The importance of hand anatomy in the accident and emergency department:
      assessment of hand anatomy knowledge in doctors in training.
AB  - Good anatomical knowledge is essential for the early recognition of severe or
      significant hand injuries in the Accident and Emergency (A&E) department, in
      particular nerve, vascular or tendon injuries. In 1992, Murphy and Olney assessed
      hand anatomy knowledge in junior doctors. We have repeated this study 16 years
      on. The 2008 cohort performed worse in response to every question asked and in
      some areas significantly so. We discuss the results in relation to the
      recognition of serious injuries and also with regards to anatomy teaching in
      medical schools and at postgraduate level.

PMID- 19587073
TI  - End-to-side nerve suture in traumatic injuries of brachial plexus: review of the
      literature and personal case series.
AB  - We used end-to-side nerve coaptation combined with standard end-to-end
      neurotisations to treat 11 patients who presented with complete (six cases) or
      incomplete (five cases) traumatic brachial plexus injuries. All patients were
      available for functional evaluation at a minimum of 2 years postoperatively. In
      three patients with shoulder abduction recovery, electromyographical studies
      (EMG) showed a contribution from the end-to-side neurotisation. In the remaining
      cases end-to-side neurotisations were unsuccessful. Our study did not demonstrate
      a reliable role for end-to-side nerve suture in brachial plexus surgery. We
      believe that at present end-to-side suture must not be a substitute for standard
      reconstructive techniques in brachial plexus surgery. Occasionally termino
      lateral nerve sutures may represent a support to standard reconstructive
      procedures especially in case of severe injuries when few undamaged donor nerves
      are available.

PMID- 19587074
TI  - Basal joint osteoarthritis of the thumb treated with Weilby arthroplasty: a
      prospective study on the early postoperative course of 106 consecutive cases.
AB  - One hundred and six consecutive cases of osteoarthritis of the trapeziometacarpal
      joint, treated by tendon interposition arthroplasty as described by Weilby, were
      followed prospectively, with assessment of pain, mobility, pinch and grip
      strength at 6, 12, 26 and 52 weeks. Patient satisfaction was reviewed at 26 and
      52 weeks. Preoperative visual analogue scores for pain averaged 65 and decreased
      postoperatively to an average of 12 at 52 weeks. The main decrease in pain
      occurred during the first 3 months after operation. Mobility was improved or
      unaltered in 82%. Average grip and pinch strength reached preoperative values (41
      kPa and 20 kPa respectively) between 12 and 26 weeks after surgery and were
      significantly greater (58 kPa and 34 kPa) at 52 weeks. Recovery after suspension
      arthroplasty takes 3-6 months, which may be a disadvantage to be considered when
      advising patients who are considering operative treatment.

PMID- 19587075
TI  - Lower trapezius muscle transfer for reconstruction of elbow extension in brachial
      plexus injuries.
AB  - Elbow extension is a prerequisite for adequate hand position. Muscle transfers
      are often employed in partial injuries of the brachial plexus, when neurological
      surgery is unlikely to achieve desired results. The posterior deltoid and
      latissimus dorsi are the two muscles most commonly used for transfer but there
      are few alternatives when these two muscles are paralysed. We now report on the
      successful transfer of the lower trapezius muscle to reconstruct triceps function
      in three patients with longstanding lesions of the brachial plexus that had not
      been previously treated surgically.

PMID- 19587077
TI  - Treatment of nonunions of the distal phalanx with olecranon bone graft.
AB  - Distal phalangeal fractures are the most common fractures of the hand but
      nonunions are unusual in the distal phalanx. Eleven patients were operated on for
      nonunions of the distal phalanx. The diagnosis of nonunion was made by the
      presence of the clinical (pain, deformity, instability) and radiological signs of
      nonunion more than 4 months after the initial injury. Three patients had
      developed infection and four of them had bone resorption after their initial
      treatments, which probably caused nonunion. Olecranon bone grafting combined with
      Kirschner wire fixation was done in all patients. The mean follow up was 7 months
      (range 5-18 months). There were no major complications at the donor or recipient
      sites. One patient had a haematoma formation at the donor site. There was
      complete radiological union of bone-grafted sites in all patients except one.
      There were no cases of pain, deformity, or instability after the treatment. The
      olecranon bone graft was found to be safe and easy to harvest. Its strong tubular
      structure replaced the distal phalanx successfully.

PMID- 19587076
TI  - Four-corner bone arthrodesis with dorsal rectangular plate: series and personal
      technique.
AB  - Controversy exists about the best method to achieve bone fusion in four-corner
      arthrodesis. Thirty-five patients who underwent this procedure by our technique
      were included in the study. Surgical indications were stage II-III SLAC wrist,
      stage II SNAC wrist and severe traumatic midcarpal joint injury. Mean follow-up
      was 4.6 years. Mean active flexion and extension were 34 degrees and 30 degrees
      respectively; grip strength recovery was 79%. Radiological consolidation was
      achieved in all cases. The mean DASH score was 23 and the postoperative pain
      improvement by visual analogue scale was statistically significant. Return to
      work was possible at 4 months for the average patient. Complications were a
      capitate fracture in one patient and the need for hardware removal in four cases.
      Four-corner bone wrist arthrodesis by dorsal rectangular plating achieves an
      acceptable preservation of range of motion with good pain relief, an excellent
      consolidation rate and minimal complications.

PMID- 19587078
TI  - Assessment of a diagnostic questionnaire and protocol for management of carpal
      tunnel syndrome.
AB  - One hundred and fifty-two patients with suspected carpal tunnel syndrome (CTS)
      completed a questionnaire, including questions about the location of
      paraesthesia, nocturnal pain, the effect of shaking the hand, relief by use of a
      wrist splint and impairment of manual dexterity. A score was derived from the
      symptom questionnaire and clinical signs including Tinel's test, Phalen's test,
      and altered sensation. Nerve conduction studies (NCS) were done in 91 cases in
      which the diagnosis of CTS was in doubt. A threshold questionnaire score was
      selected as indicating a diagnosis of CTS. Sixty-six patients were predicted to
      have CTS. When compared with the results of NCS this score had a specificity of
      67% and sensitivity of 82%. Ninety-five patients underwent carpal tunnel release.
      A management model has been developed based on the questionnaire score for
      symptoms and signs.

PMID- 19587079
TI  - Reducing the economic impact of carpal tunnel surgery.
AB  - A nurse-led carpal tunnel service was started in Leicester in 1999. Many
      developments in the service have been patient-driven. A large proportion of our
      patients are not salaried and many had expressed concerns about the amount of
      time taken off work after surgery. This therefore prompted us to encourage
      immediate hand function after surgery. Subsequently, in 494 patients studied
      prospectively, we have seen 93% of patients return to work by 2 weeks and 99% by
      4 weeks. This has obvious benefits in terms of reducing loss of income.
      Furthermore there is potential for considerable economic savings.

PMID- 19587080
TI  - Clinical implications of cerebral reorganisation after primary digital flexor
      tendon repair.
AB  - After flexor tendon injury, most attention is given to the quality of the tendon
      repair and postoperative early passive dynamic mobilisation. Schemes for active
      mobilisation have been developed to prevent tendon adhesions and joint stiffness.
      This paper describes five patients to demonstrate the cerebral consequences of
      immobilisation allowing only passive movements, which implies a prolonged absence
      of actual motor commands. At the end of such immobilisation, PET imaging revealed
      reduced blood flow in specific motor areas, associated with temporary loss of
      efficient motor control. Effective motor control was regained after active
      flexion exercises which was reflected in normalised cerebral activations. This
      suggests that temporary, reversible cerebral dysfunction may affect the outcome
      of flexor tendon injuries.

PMID- 19587081
TI  - Is the Patient Outcomes Of Surgery (POS)-Hand/Arm questionnaire a reliable, valid
      and responsive measurement of patient-based outcomes in hand and upper limb
      surgery?
AB  - The purpose of our study was to evaluate a new region-specific outcome measure in
      hand and upper limb surgery: the Patient Outcomes of Surgery (POS)-Hand/Arm
      questionnaire using the generic Short Form Health Survey (SF)-36 questionnaire as
      a 'gold standard' comparative measure. The POS-Hand/Arm preop questionnaire and
      the SF-36 questionnaire were completed by 214 patients on the day of their hand
      or upper limb surgery; and a postop POS-Hand/Arm and the SF-36 questionnaire were
      completed by patients 3 months after their initial surgery. The POS-Hand/Arm
      questionnaire responses were psychometrically evaluated and it was shown to have
      high internal consistency; high total-item correlations; signification scale
      correlations with the SF-36; and a low proportion of missing data. The POS
      Hand/Arm questionnaire is a psychometrically sound instrument that can be used
      pre- and post-surgery to evaluate patient-based outcomes for a wide range of
      conditions in hand and upper limb surgery.

PMID- 19587082
TI  - The effect of tissue culture on suture holding strength and degradation in canine
      tendon.
AB  - The purpose of this study was to assess tendon metabolism and suture pull-out
      strength after simple tendon suture in a tissue culture model. One hundred and
      twelve flexor digitorum profundus tendons from 28 dogs were cultured for 7, 14,
      or 21 days with or without a static tensile load. In both groups increased levels
      of matrix metalloproteinase (MMP) mRNA was noted. Suture pull-out strength did
      not decrease during tissue culture. While the presence of a static load had no
      effect on the pull-out strength, it did affect MMP mRNA expression. This tissue
      culture model could be useful in studying the effect of factors on the tendon
      suture interface.

PMID- 19587084
TI  - Activation of the gut-brain axis by dietary glutamate and physiologic
      significance in energy homeostasis.
AB  - l-Glutamate is a multifunctional amino acid involved in taste perception,
      intermediary metabolism, and excitatory neurotransmission. In addition, recent
      studies have uncovered new roles for l-glutamate in gut-brain axis activation and
      energy homeostasis. l-Glutamate receptors and their cellular transduction
      molecules have recently been identified in gut epithelial cells. Stimulation of
      such l-glutamate receptors by luminal l-glutamate activates vagal afferent nerve
      fibers and then parts of the brain that are targeted directly or indirectly by
      these vagal inputs. Notably, 3 areas of the brain-the medial preoptic area, the
      hypothalamic dorsomedial nucleus, and the habenular nucleus-are activated by
      intragastric l-glutamate but not by glucose or sodium chloride. Furthermore, the
      chronic, ad libitum ingestion of a palatable solution of monosodium l-glutamate
      (1% wt:vol) by rats has also been found to reduce weight gain, fat deposition,
      and plasma leptin concentrations compared with rats that ingest water alone. No
      difference in food intake was observed. Such effects may also be vagally
      mediated. Together, such findings contribute to the growing knowledge base that
      indicates that l-glutamate signaling via taste and gut l-glutamate receptors may
      influence multiple physiologic functions, such as thermoregulation and energy
      homeostasis.

PMID- 19587083
TI  - Prospective study of meat intake and dietary nitrates, nitrites, and nitrosamines
      and risk of adult glioma.
AB  - BACKGROUND: The hypothesis that nitrosamine exposure may increase the risk of
      glioma has been circulating for several decades, but testing it has been
      difficult because of the ubiquitous nature of nitrosamine exposure. Diet has been
      the focus of many studies because it can substantially influence nitrosamine
      exposure, mostly from the endogenous formation of nitrosamines based on intake of
      nitrite and nitrate. OBJECTIVE: The objective was to examine the relation between
      intakes of meats, nitrate, nitrite, and 2 nitrosamines [nitrosodimethylamine
      (NDMA) and nitrosopyrolidine (NPYR)] and glioma risk in a prospective analysis.
      METHODS: Data from 3 US prospective cohort studies were combined for this
      analysis; 335 glioma cases were diagnosed during < or =24 y of follow-up. Dietary
      intake was assessed with food-frequency questionnaires. Nitrate, nitrite, and
      nitrosamine values were calculated based on published values of these nutrients
      in various foods over different periods in time. Cox proportional hazards models
      were used to estimate incidence rate ratios (RRs) and 95% CIs. Estimates from
      each cohort were pooled by using a random-effects model. RESULTS: Risk of glioma
      was not elevated among individuals in the highest intake category of total
      processed meats (RR: 0.92; 95% CI: 0.48, 1.77), nitrate (RR: 1.02; 95% CI: 0.66,
      1.58), nitrites (RR: 1.26; 95% CI: 0.89, 1.79), or NDMA (RR: 0.88; 95% CI: 0.57,
      1.36) compared with the lowest category. No effect modification was observed by
      intake of vitamins C or E or other antioxidant measures. CONCLUSION: We found no
      suggestion that intake of meat, nitrate, nitrite, or nitrosamines is related to
      the risk of glioma.

PMID- 19587085
TI  - Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor
      genes.
AB  - BACKGROUND: The TAS1R1 and TAS1R3 G protein-coupled receptors are believed to
      function in combination as a heteromeric glutamate taste receptor in humans.
      OBJECTIVE: We hypothesized that variations in the umami perception of glutamate
      would correlate with variations in the sequence of these 2 genes, if they
      contribute directly to umami taste. DESIGN: In this study, we first characterized
      the general sensitivity to glutamate in a sample population of 242 subjects. We
      performed these experiments by sequencing the coding regions of the genomic
      TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested
      repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role
      of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression
      assay. RESULTS: A subset of subjects displays extremes of sensitivity, and a
      battery of different psychophysical tests validated this observation. Statistical
      analysis showed that the rare T allele of single nucleotide polymorphism (SNP)
      R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other
      suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H,
      which both resulted in an approximate doubling of umami ratings of 200 mmol
      MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer
      receptor in umami taste by recording responses, specifically to l-glutamate and
      inosine 5'-monophosphate (IMP) mixtures in a heterologous expression assay in HEK
      (human embryonic kidney) T cells. CONCLUSIONS: There is a reliable and valid
      variation in human umami taste of l-glutamate. Variations in perception of umami
      taste correlated with variations in the human TAS1R3 gene. The putative human
      taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the
      ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste
      perception.

PMID- 19587086
TI  - Plasma citrulline is a biomarker of enterocyte mass and an indicator of
      parenteral nutrition in HIV-infected patients.
AB  - BACKGROUND: Plasma citrulline is a biomarker of enterocyte mass and function in
      humans. OBJECTIVE: We evaluated citrulline in the reemerging context of diarrhea
      in HIV-infected patients receiving highly active antiretroviral therapy. DESIGN:
      This study prospectively measured citrulline in 6 groups of HIV-1 patients (n =
      115): 1) undetectable viral load without chronic diarrhea (a; n = 40) and with
      protease inhibitor-associated toxic chronic diarrhea (b; n = 26), 2) detectable
      viral load and CD4 > 200/mm(3) without (a; n = 6) and with (b; n = 11) chronic
      diarrhea, and 3) detectable viral load and CD4 <200/mm(3) without chronic
      diarrhea (a; n = 7) and with opportunistic intestinal infections or HIV
      enteropathy (b; n = 25). The influence of diarrhea on citrulline was assessed by
      comparing the a and b subgroups with healthy control subjects (n = 100). RESULTS:
      Citrulline was slightly decreased (22-30 micromol/L) in groups 1b and 2b and was
      <22 micromol/L in 19 of 25 patients in group 3b. In group 3b, a citrulline
      concentration <10 micromol/L was associated with a clinical indication for
      parenteral nutrition (n = 6 of 8 compared with 2 of 17 if the citrulline
      concentration was >10 micromol/L; P < 0.05). Citrulline correlated positively
      with albumin (P < 0.01) and BMI (P < 0.05) and negatively with C-reactive protein
      (P < 0.01). When antiinfectious and nutritional therapies were successful (n = 18
      of 25), citrulline normalized in 2-12 wk. Neither chronic hepatic or pancreatic
      disease nor lipodystrophy and the metabolic syndrome affected citrulline.
      Compared with control subjects (38 +/- 8 micromol/L), patients without chronic
      diarrhea (groups 1a, 2a, and 3a) had normal citrulline concentrations (36 +/- 6
      micromol/L). CONCLUSIONS: Plasma citrulline is a reliable biomarker of enterocyte
      functional mass in HIV patients. Citrulline does not allow the etiologic
      diagnosis of enteropathy, but it can discriminate between protease inhibitor
      toxic diarrhea and infectious enteropathy and quantify the functional
      consequences, which makes it an objective tool for indicating the need for
      parenteral nutrition.

PMID- 19587087
TI  - Association of cholesterol oxidation and abnormalities in fatty acid metabolism
      in cystic fibrosis.
AB  - BACKGROUND: Disarrangement in fatty acids and oxidative stress are features of
      cystic fibrosis. Cholesterol is very sensitive to oxidative stress. OBJECTIVES:
      The objectives were to examine whether cholesterol oxidation products are altered
      in cystic fibrosis and whether they are associated with fatty acids and with
      characteristics of the disease state. DESIGN: 7-Ketocholesterol and 7beta
      hydroxycholesterol (prototype molecules of free radical-mediated cholesterol
      oxidation) and the fatty acid profile were assessed by mass spectrometry in
      patients and in sex- and age-matched control subjects. RESULTS: In a comparison
      with control subjects, mean (+/-SD) cholesterol oxidation was higher (7
      ketocholesterol: 11.31 +/- 5.1 compared with 8.33 +/- 5.5 ng/mL, P = 0.03; 7beta
      hydroxycholesterol: 14.5 +/- 6.8 compared with 9.7 +/- 4.1 ng/mL, P = 0.004),
      total saturated fatty acids were higher (31.90 +/- 1.93% compared with 30.31 +/-
      0.98%, P < 0.001), monounsaturated fatty acids were higher (29.14 +/- 3.85%
      compared with 25.88 +/- 2.94%, P = 0.004), omega-6 (n-6) polyunsaturated fatty
      acids were lower (34.84 +/- 4.77 compared with 39.68 +/- 2.98%, P < 0.0001), and
      omega-3 (n-3) polyunsaturated fatty acids were comparable in patients with cystic
      fibrosis. Oxysterols were inversely associated with 24:0 and 18:2 omega-6 fatty
      acids but did not correlate with the increased oleic acid or with any of the
      omega-3 fatty acids. CONCLUSIONS: Cystic fibrosis is characterized by relevant
      cholesterol oxidation that is associated with an abnormal fatty acid profile. The
      interplay between oxysterols and fatty acids potentially provides insight into
      the biological mechanisms that underlie this complex disease.

PMID- 19587088
TI  - Coffee drinking in middle age is not associated with cognitive performance in old
      age.
AB  - BACKGROUND: The lack of effective disease-modifying treatments highlights the
      need for research on the prevention of dementia. It has been suggested that
      coffee has a protective effect on cognitive performance in old age, but only some
      of the previous studies have shown this association. OBJECTIVE: The aim of our
      study was to analyze the potential association between coffee drinking in middle
      age and cognitive performance in old age in a large sample of Finnish twins.
      DESIGN: Coffee consumption and other baseline variables of 2606 middle-aged
      Finnish twins were assessed in 1975 and 1981 by postal questionnaires. After the
      median follow-up of 28 y, their cognitive status was measured by using a
      validated telephone interview questionnaire. RESULTS: Coffee consumption was high
      and associated with educational level and several other baseline variables. After
      adjustment for these variables, linear regression analysis showed that coffee
      consumption was not an independent predictor of cognitive performance in old age
      (beta = -0.12 test score units per coffee cup; 95% CI: -0.27, 0.04). No
      consistent differences in coffee consumption and cognitive score were observed
      within discordant twin pairs. Also, coffee drinking did not affect the risk of
      mild cognitive impairment or dementia. CONCLUSIONS: Coffee drinking is associated
      with many sociodemographic and health variables, but our results do not support
      an independent role of coffee in the pathogenesis of cognitive decline and
      dementia.

PMID- 19587090
TI  - Site-specific concentrations of carotenoids in adipose tissue: relations with
      dietary and serum carotenoid concentrations in healthy adults.
AB  - BACKGROUND: Dietary carotenoids are related to a decreased risk of certain
      diseases. Serum and adipose tissue carotenoid concentrations are used as
      biomarkers of intake. OBJECTIVES: The objectives of this study were to evaluate
      site-specific concentrations of carotenoids in adipose tissue and to examine
      relations between carotenoid concentrations in the diet, serum, and adipose
      tissue. DESIGN: Healthy adults (12 women and 13 men) participated in this cross
      sectional study. Dietary carotenoids over the past year were assessed with a food
      frequency questionnaire. Serum and adipose tissue biopsy samples were collected
      from the abdomen, buttock, and inner thigh for the measurement of carotenoids by
      HPLC. RESULTS: Many adipose carotenoids were inversely related to percentage body
      fat, although lycopene was the only carotenoid inversely correlated with all 3
      sites. Most of the carotenoids were significantly higher in the abdominal adipose
      tissue than in the thigh (P < 0.05). Concentrations of alpha-carotene, beta
      carotene, 5-cis-lycopene, and total carotenoids were significantly higher in the
      buttocks than in the thigh (P < 0.05). Concentrations of alpha-carotene, cis
      lycopene, and lutein (with or without zeaxanthin) were significantly higher in
      the abdomen than in the buttocks (P < 0.05). Dietary intake was significantly
      correlated with serum concentrations of alpha-carotene, beta-carotene, beta
      cryptoxanthin, and total carotenoids. Carotenoid intake was significantly
      correlated with adipose tissue concentrations of alpha-carotene, beta-carotene,
      beta-cryptoxanthin, cis-lycopene, and total carotenoids (P < 0.05) but varied by
      site. Of all the adipose tissue sites evaluated, the abdomen showed the strongest
      correlation with long-term dietary carotenoid intakes and with serum (indicator
      of short-term intake) for most carotenoids. CONCLUSIONS: Body fat may influence
      the tissue distribution of carotenoids. Abdominal adipose tissue carotenoid
      concentrations may be a useful indicator of carotenoid status.

PMID- 19587089
TI  - Dietary patterns and breast cancer risk in women participating in the Black
      Women's Health Study.
AB  - BACKGROUND: No studies have examined dietary patterns and breast cancer risk in a
      large cohort of African American women. OBJECTIVE: We investigated the
      association between dietary patterns and breast cancer risk in the Black Women's
      Health Study. DESIGN: This is a prospective cohort study of 50,778 participants
      followed biennially from 1995 through 2007. During 443,742 person-years of follow
      up, 1094 incident cases of breast cancer were identified. Factor analysis was
      used to derive food patterns based on 69 food variables. We used Cox regression
      models to obtain incident rate ratios (IRRs) for breast cancer in relation to
      quintiles of each of the 2 dietary patterns, with adjustment for other breast
      cancer risk factors. RESULTS: Through factor analysis, we identified 2 dietary
      patterns: Western (refined grains, processed meat, and sweets) and prudent (whole
      grains, vegetables, fruit, and fish). The prudent diet was weakly associated with
      lower breast cancer risk overall; P for trend = 0.06. In analyses stratified by
      body mass index (BMI; in kg/m(2)), the prudent dietary pattern was associated
      with a significantly lower risk of breast cancer in women with a BMI <25 (IRR:
      0.64; 95% CI: 0.43, 0.93; P for trend = 0.01). The prudent dietary pattern was
      also associated with a significantly lower risk of breast cancer in premenopausal
      women (IRR: 0.70; 95% CI: 0.52, 0.96; P for trend = 0.01), and we found a
      significant inverse association for the prudent dietary pattern and estrogen
      receptor-negative breast cancer (IRR: 0.52; 95% CI: 0.28, 0.94; P for trend
      <0.01). CONCLUSION: Our findings suggest that the prudent dietary pattern may
      protect against breast cancer in some black women.

PMID- 19587091
TI  - Metabolic fate and function of dietary glutamate in the gut.
AB  - Glutamate is a main constituent of dietary protein and is also consumed in many
      prepared foods as an additive in the form of monosodium glutamate. Evidence from
      human and animal studies indicates that glutamate is a major oxidative fuel for
      the gut and that dietary glutamate is extensively metabolized in first pass by
      the intestine. Glutamate also is an important precursor for bioactive molecules,
      including glutathione, and functions as a key neurotransmitter. The dominant role
      of glutamate as an oxidative fuel may have therapeutic potential for improving
      function of the infant gut, which exhibits a high rate of epithelial cell
      turnover. Our recent studies in infant pigs show that when glutamate is fed at
      higher (4-fold) than normal dietary quantities, most glutamate molecules are
      either oxidized or metabolized by the mucosa into other nonessential amino acids.
      Glutamate is not considered to be a dietary essential, but recent studies suggest
      that the level of glutamate in the diet can affect the oxidation of some
      essential amino acids, namely leucine. Given that substantial oxidation of
      leucine occurs in the gut, ongoing studies are investigating whether dietary
      glutamate affects the oxidation of leucine in the intestinal epithelial cells.
      Our studies also suggest that at high dietary intakes, free glutamate may be
      absorbed by the stomach as well as the small intestine, thus implicating the
      gastric mucosa in the metabolism of dietary glutamate. Glutamate is a key
      excitatory amino acid, and metabolism and neural sensing of dietary glutamate in
      the developing gastric mucosa, which is poorly developed in premature infants,
      may play a functional role in gastric emptying. These and other recent reports
      raise the question as to the metabolic role of glutamate in gastric function. The
      physiologic significance of glutamate as an oxidative fuel and its potential role
      in gastric function during infancy are discussed.

PMID- 19587092
TI  - Genetic susceptibility to the development and progression of breast cancer
      associated with polymorphism of cell cycle and ubiquitin ligase genes.
AB  - Tumor levels of the cell cycle regulators cyclin E and p27 correlate strongly
      with survival in breast cancer patients and are specifically regulated by the
      ubiquitin ligases hCDC4 and SKP2. This study was to explore whether genetic
      susceptibility to breast cancer is associated with polymorphism of these genes
      and whether gene-gene and gene-risk factor [i.e. full-term pregnancy (FTP)]
      interactions are important in determining cancer risk. A two-stage case-control
      study based on single-nucleotide polymorphisms was performed. The first study
      (560 cases and 1122 controls) was to define the contribution of cell cycle and
      ubiquitin ligase genes to cancer susceptibility. The second study (926 cases and
      923 controls) was to confirm the association identified in the first stage and to
      map the variant alleles. Increased breast cancer risk was associated with both
      polymorphism of hCDC4 and a joint effect of cyclin E and hCDC4. These
      associations were more significant in nulliparous women, and cancer risk
      associated with a lower number of FTPs was only seen in women with a higher
      number of high-risk genotypes, providing support for an effect of gene-risk
      factor interaction in determining susceptibility. Sequence variants of intron 2
      in hCDC4 were found to be the most significant polymorphism and high-stage
      estrogen receptor (ER)-negative patients carrying the homozygous variant genotype
      manifested significantly poorer survival. This study concludes that polymorphism
      of hCDC4 is a risk factor for breast cancer development by interacting with
      either cyclin E or FTP and may also prove useful in predicting progression of
      patients with high-stage and ER-negative breast cancers.

PMID- 19587093
TI  - Etoposide induces MLL rearrangements and other chromosomal abnormalities in human
      embryonic stem cells.
AB  - MLL rearrangements are hallmark genetic abnormalities in infant leukemia known to
      arise in utero. They can be induced during human prenatal development upon
      exposure to etoposide. We also hypothesize that chronic exposure to etoposide
      might render cells more susceptible to other genomic insults. Here, for the first
      time, human embryonic stem cells (hESCs) were used as a model to test the effects
      of etoposide on human early embryonic development. We addressed whether: (i) low
      doses of etoposide promote MLL rearrangements in hESCs and hESCs-derived
      hematopoietic cells; (ii) MLL rearrangements are sufficient to confer hESCs with
      a selective growth advantage and (iii) continuous exposure to low doses of
      etoposide induces hESCs to acquire other chromosomal abnormalities. In contrast
      to cord blood-derived CD34(+) and hESC-derived hematopoietic cells, exposure of
      undifferentiated hESCs to a single low dose of etoposide induced a pronounced
      cell death. Etoposide induced MLL rearrangements in hESCs and their hematopoietic
      derivatives. After long-term culture, the proportion of hESCs harboring MLL
      rearrangements diminished and neither cell cycle variations nor genomic
      abnormalities were observed in the etoposide-treated hESCs, suggesting that MLL
      rearrangements are insufficient to confer hESCs with a selective
      proliferation/survival advantage. However, continuous exposure to etoposide
      induced MLL breaks and primed hESCs to acquire other major karyotypic
      abnormalities. These data show that chronic exposure of developmentally early
      stem cells to etoposide induces MLL rearrangements and make hESCs more prone to
      acquire other chromosomal abnormalities than postnatal CD34(+) cells, linking
      embryonic genotoxic exposure to genomic instability.

PMID- 19587095
TI  - Dual role for Id2 in chemical carcinogen-induced skin tumorigenesis.
AB  - Inhibitor of DNA binding 2 (Id2) is a negative regulator of basic helix-loop
      helix transcription factors and is involved in the control of cellular
      differentiation and proliferation. By using a two-step chemical carcinogenesis
      protocol, we evaluated the role of Id2 in skin tumor formation in mice. Twenty
      weeks after the initiation, the number of tumors formed in the Id2(-/-) mice was
      3.5-fold higher than that in their wild-type littermates, whereas the diameter of
      tumors in the Id2(-/-) mice was about half of that of the tumors in the wild-type
      mice. In the Id2(-/-) mice, epidermal gammadelta T cells, which play a key role
      in immunosurveillance against skin tumor development, were barely detectable.
      Although histological analyses demonstrated no apparent difference in tumor cell
      type, tumor vessel formation or apoptosis, the proportion of proliferating cells
      was reduced in the tumors in the Id2(-/-) mice compared with those in the wild
      type mice. In the wild-type mice, the expression of Id2 was enhanced in skin
      tumors compared with that in ear epidermal cells. Biochemical analysis
      demonstrated that cyclin D1 was reduced at the protein level in the tumors in the
      Id2(-/-) mice, whereas other factors such as cyclin E and p27 were not altered
      significantly. Our results reveal that Id2 plays a dual role in skin
      tumorigenesis by suppressing tumor development through the establishment of
      epidermal gammadelta T cell-mediated skin immunosurveillance and by promoting
      tumor cell proliferation via the control of the cyclin D1 protein level.

PMID- 19587094
TI  - The prostaglandin receptor EP2 activates multiple signaling pathways and beta
      arrestin1 complex formation during mouse skin papilloma development.
AB  - Prostaglandin E(2) (PGE(2)) is elevated in many tumor types, but PGE(2)'s
      contributions to tumor growth are largely unknown. To investigate PGE(2)'s roles,
      the contributions of one of its receptors, EP2, were studied using the mouse skin
      initiation/promotion model. Initial studies indicated that protein kinase A
      (PKA), epidermal growth factor receptor (EGFR) and several effectors-cyclic
      adenosine 3',5'-monophosphate response element-binding protein (CREB), H-Ras,
      Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2
      were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas
      and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased
      papilloma formation. EP2's contributions to the activation of these pathways and
      papilloma development were determined by inhibiting endogenous TPA-induced PGE(2)
      production with indomethacin (Indo) and concomitantly treating with the EP2
      agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo
      treated mice and increased cyclic adenosine 3',5'-monophosphate and PKA
      activation as measured by p-CREB formation. CAY treatment also increased EGFR and
      Src activation and their inhibition by AG1478 and PP2 indicated that Src was
      upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478
      decreased their activation indicating EGFR being upstream. Supporting EP2's
      contribution, EP2-/- mice exhibited 65% fewer papillomas and reduced Src, EGFR, H
      Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of
      EGFR has been reported to involve Src's activation via a GPCR-beta-arrestin-Src
      complex. Indeed, immunoprecipitation of beta-arrestin1 or p-Src indicated the
      presence of an EP2-beta-arrestin1-p-Src complex in papillomas. The data indicated
      that EP2 contributed to tumor formation via activation of PKA and EGFR and that
      EP2 formed a complex with beta-arrestin1 and Src that contributed to signaling
      and/or EP2 desensitization.

PMID- 19587096
TI  - (Homo)glutathione depletion modulates host gene expression during the symbiotic
      interaction between Medicago truncatula and Sinorhizobium meliloti.
AB  - Under nitrogen-limiting conditions, legumes interact with symbiotic rhizobia to
      produce nitrogen-fixing root nodules. We have previously shown that glutathione
      and homoglutathione [(h)GSH] deficiencies impaired Medicago truncatula symbiosis
      efficiency, showing the importance of the low M(r) thiols during the nodulation
      process in the model legume M. truncatula. In this study, the plant
      transcriptomic response to Sinorhizobium meliloti infection under (h)GSH
      depletion was investigated using cDNA-amplified fragment length polymorphism
      analysis. Among 6,149 expression tags monitored, 181 genes displayed significant
      differential expression between inoculated control and inoculated (h)GSH depleted
      roots. Quantitative reverse transcription polymerase chain reaction analysis
      confirmed the changes in mRNA levels. This transcriptomic analysis shows a down
      regulation of genes involved in meristem formation and a modulation of the
      expression of stress-related genes in (h)GSH-depleted plants. Promoter-beta
      glucuronidase histochemical analysis showed that the putative MtPIP2 aquaporin
      might be up-regulated during nodule meristem formation and that this up
      regulation is inhibited under (h)GSH depletion. (h)GSH depletion enhances the
      expression of salicylic acid (SA)-regulated genes after S. meliloti infection and
      the expression of SA-regulated genes after exogenous SA treatment. Modification
      of water transport and SA signaling pathway observed under (h)GSH deficiency
      contribute to explain how (h)GSH depletion alters the proper development of the
      symbiotic interaction.

PMID- 19587097
TI  - Evidence that light, carbon dioxide, and oxygen dependencies of leaf isoprene
      emission are driven by energy status in hybrid aspen.
AB  - Leaf isoprene emission scales positively with light intensity, is inhibited by
      high carbon dioxide (CO(2)) concentrations, and may be enhanced or inhibited by
      low oxygen (O(2)) concentrations, but the mechanisms of environmental regulation
      of isoprene emission are still not fully understood. Emission controls by
      isoprene synthase, availability of carbon intermediates, or energetic cofactors
      have been suggested previously. In this study, we asked whether the short-term
      (tens of minutes) environmental control of isoprene synthesis results from
      alterations in the immediate isoprene precursor dimethylallyldiphosphate (DMADP)
      pool size, and to what extent DMADP concentrations are affected by the supply of
      carbon and energetic metabolites. A novel in vivo method based on
      postillumination isoprene release was employed to measure the pool size of DMADP
      simultaneously with the rates of isoprene emission and net assimilation at
      different light intensities and CO(2) and O(2) concentrations. Both net
      assimilation and isoprene emission rates increased hyperbolically with light
      intensity. The photosynthetic response to CO(2) concentration was also
      hyperbolic, while the CO(2) response curve of isoprene emission exhibited a
      maximum at close to CO(2) compensation point. Low O(2) positively affected both
      net assimilation and isoprene emission. In all cases, the variation in isoprene
      emission was matched with changes in DMADP pool size. The results of these
      experiments suggest that DMADP pool size controls the response of isoprene
      emission to light intensity and to CO(2) and O(2) concentrations and that the
      pool size is determined by the level of energetic metabolites generated in
      photosynthesis.

PMID- 19587098
TI  - Pleiotropic modulation of carbon and nitrogen metabolism in Arabidopsis plants
      overexpressing the NAD kinase2 gene.
AB  - Nicotinamide nucleotides (NAD and NADP) are important cofactors in many metabolic
      processes in living organisms. In this study, we analyzed transgenic Arabidopsis
      (Arabidopsis thaliana) plants that overexpress NAD kinase2 (NADK2), an enzyme
      that catalyzes the synthesis of NADP from NAD in chloroplasts, to investigate the
      impacts of altering NADP level on plant metabolism. Metabolite profiling revealed
      that NADP(H) concentrations were proportional to NADK activity in NADK2
      overexpressors and in the nadk2 mutant. Several metabolites associated with the
      Calvin cycle were also higher in the overexpressors, accompanied by an increase
      in overall Rubisco activity. Furthermore, enhanced NADP(H) production due to
      NADK2 overexpression increased nitrogen assimilation. Glutamine and glutamate
      concentrations, as well as some other amino acids, were higher in the
      overexpressors. These results indicate that overexpression of NADK2 either
      directly or indirectly stimulates carbon and nitrogen assimilation in Arabidopsis
      under restricted conditions. Importantly, since neither up-regulation nor down
      regulation of NADK2 activity affected the sum amount of NAD and NADP or the redox
      state, the absolute level of NADP and/or the NADP/NAD ratio likely plays a key
      role in regulating plant metabolism.

PMID- 19587099
TI  - Photosystem II and pigment dynamics among ecotypes of the green alga
      Ostreococcus.
AB  - We investigated the photophysiological responses of three ecotypes of the
      picophytoplankter Ostreococcus and a larger prasinophyte Pyramimonas obovata to a
      sudden increase in light irradiance. The deepwater Ostreococcus sp. RCC809 showed
      very high susceptibility to primary photoinactivation, likely a consequence of
      high oxidative stress, which may relate to the recently noted plastid terminal
      oxidase activity in this strain. The three Ostreococcus ecotypes were all capable
      of deploying modulation of the photosystem II repair cycle in order to cope with
      the light increase, but the effective clearance of photoinactivated D1 protein
      appeared to be slower in the deepwater Ostreococcus sp. RCC809, suggesting that
      this step is rate limiting in the photosystem II repair cycle in this strain.
      Moreover, the deepwater Ostreococcus accumulated lutein and showed substantial
      use of the xanthophyll cycle under light stress, demonstrating its high
      sensitivity to light fluctuations. The sustained component of the
      nonphotochemical quenching of fluorescence correlated well with the xanthophyll
      deepoxidation activity. Comparisons with the larger prasinophyte P. obovata
      suggest that the photophysiology of Ostreococcus ecotypes requires high
      photosystem II repair rates to counter a high susceptibility to
      photoinactivation, consistent with low pigment package effects in their minute
      sized cells.

PMID- 19587101
TI  - A phosphofructokinase B-type carbohydrate kinase family protein, NARA5, for
      massive expressions of plastid-encoded photosynthetic genes in Arabidopsis.
AB  - To date, there have been no reports on screening for mutants defective in the
      massive accumulation of Rubisco in higher plants. Here, we describe a screening
      method based on the toxic accumulation of ammonia in the presence of methionine
      sulfoximine, a specific inhibitor of glutamine synthetase, during
      photorespiration initiated by the oxygenase reaction of Rubisco in Arabidopsis
      (Arabidopsis thaliana). Five recessive mutants with decreased amounts of Rubisco
      were identified and designated as nara mutants, as they contained a mutation in
      genes necessary for the achievement of Rubisco accumulation. The nara5-1 mutant
      showed markedly lower levels of plastid-encoded photosynthetic proteins,
      including Rubisco. Map-based cloning revealed that NARA5 encoded a chloroplast
      phosphofructokinase B-type carbohydrate kinase family protein of unknown
      function. The NARA5 protein fused to green fluorescent protein localized in
      chloroplasts. We conducted expression analyses of photosynthetic genes during
      light-induced greening of etiolated seedlings of nara5-1 and the T-DNA insertion
      mutant, nara5-2. Our results strongly suggest that NARA5 is indispensable for
      hyperexpression of photosynthetic genes encoded in the plastid genome,
      particularly rbcL.

PMID- 19587100
TI  - Enhancement of carotenoid biosynthesis in transplastomic tomatoes by induced
      lycopene-to-provitamin A conversion.
AB  - Carotenoids are essential pigments of the photosynthetic apparatus and an
      indispensable component of the human diet. In addition to being potent
      antioxidants, they also provide the vitamin A precursor beta-carotene. In tomato
      (Solanum lycopersicum) fruits, carotenoids accumulate in specialized plastids,
      the chromoplasts. How the carotenoid biosynthetic pathway is regulated and what
      limits total carotenoid accumulation in fruit chromoplasts is not well
      understood. Here, we have introduced the lycopene beta-cyclase genes from the
      eubacterium Erwinia herbicola and the higher plant daffodil (Narcissus
      pseudonarcissus) into the tomato plastid genome. While expression of the
      bacterial enzyme did not strongly alter carotenoid composition, expression of the
      plant enzyme efficiently converted lycopene, the major storage carotenoid of the
      tomato fruit, into provitamin A (beta-carotene). In green leaves of the
      transplastomic tomato plants, more lycopene was channeled into the beta-branch of
      carotenoid biosynthesis, resulting in increased accumulation of xanthophyll cycle
      pigments and correspondingly reduced accumulation of the alpha-branch xanthophyll
      lutein. In fruits, most of the lycopene was converted into beta-carotene with
      provitamin A levels reaching 1 mg per g dry weight. Unexpectedly, transplastomic
      tomatoes also showed a >50% increase in total carotenoid accumulation, indicating
      that lycopene beta-cyclase expression enhanced the flux through the pathway in
      chromoplasts. Our results provide new insights into the regulation of carotenoid
      biosynthesis and demonstrate the potential of plastids genome engineering for the
      nutritional enhancement of food crops.

PMID- 19587102
TI  - Structural and enzymatic characterization of Os3BGlu6, a rice beta-glucosidase
      hydrolyzing hydrophobic glycosides and (1->3)- and (1->2)-linked disaccharides.
AB  - Glycoside hydrolase family 1 (GH1) beta-glucosidases play roles in many processes
      in plants, such as chemical defense, alkaloid metabolism, hydrolysis of cell wall
      derived oligosaccharides, phytohormone regulation, and lignification. However,
      the functions of most of the 34 GH1 gene products in rice (Oryza sativa) are
      unknown. Os3BGlu6, a rice beta-glucosidase representing a previously
      uncharacterized phylogenetic cluster of GH1, was produced in recombinant
      Escherichia coli. Os3BGlu6 hydrolyzed p-nitrophenyl (pNP)-beta-d-fucoside
      (k(cat)/K(m) = 67 mm(-1) s(-1)), pNP-beta-d-glucoside (k(cat)/K(m) = 6.2 mm(-1)
      s(-1)), and pNP-beta-d-galactoside (k(cat)/K(m) = 1.6 mm(-1)s(-1)) efficiently
      but had little activity toward other pNP glycosides. It also had high activity
      toward n-octyl-beta-d-glucoside and beta-(1-->3)- and beta-(1-->2)-linked
      disaccharides and was able to hydrolyze apigenin beta-glucoside and several other
      natural glycosides. Crystal structures of Os3BGlu6 and its complexes with a
      covalent intermediate, 2-deoxy-2-fluoroglucoside, and a nonhydrolyzable substrate
      analog, n-octyl-beta-d-thioglucopyranoside, were solved at 1.83, 1.81, and 1.80 A
      resolution, respectively. The position of the covalently trapped 2-F-glucosyl
      residue in the enzyme was similar to that in a 2-F-glucosyl intermediate complex
      of Os3BGlu7 (rice BGlu1). The side chain of methionine-251 in the mouth of the
      active site appeared to block the binding of extended beta-(1-->4)-linked
      oligosaccharides and interact with the hydrophobic aglycone of n-octyl-beta-d
      thioglucopyranoside. This correlates with the preference of Os3BGlu6 for short
      oligosaccharides and hydrophobic glycosides.

PMID- 19587103
TI  - Overexpressing AtPAP15 enhances phosphorus efficiency in soybean.
AB  - Low phosphorus (P) availability is a major constraint to crop growth and
      production, including soybean (Glycine max), on a global scale. However, 50% to
      80% of the total P in agricultural soils exists as organic phosphate, which is
      unavailable to plants unless hydrolyzed to release inorganic phosphate. One
      strategy for improving crop P nutrition is the enhanced activity of acid
      phosphatases (APases) to obtain or remobilize inorganic phosphate from organic P
      sources. In this study, we overexpressed an Arabidopsis (Arabidopsis thaliana)
      purple APase gene (AtPAP15) containing a carrot (Daucus carota) extracellular
      targeting peptide in soybean hairy roots and found that the APase activity was
      increased by 1.5-fold in transgenic hairy roots. We subsequently transformed
      soybean plants with AtPAP15 and studied three homozygous overexpression lines of
      AtPAP15. The three transgenic lines exhibited significantly improved P efficiency
      with 117.8%, 56.5%, and 57.8% increases in plant dry weight, and 90.1%, 18.2%,
      and 62.6% increases in plant P content, respectively, as compared with wild-type
      plants grown on sand culture containing phytate as the sole P source. The
      transgenic soybean lines also exhibited a significant level of APase and phytase
      activity in leaves and root exudates, respectively. Furthermore, the transgenic
      lines exhibited improved yields when grown on acid soils, with 35.9%, 41.0%, and
      59.0% increases in pod number per plant, and 46.0%, 48.3%, and 66.7% increases in
      seed number per plant. Taken together, to our knowledge, our study is the first
      report on the improvement of P efficiency in soybean through constitutive
      expression of a plant APase gene. These findings could have significant
      implications for improving crop yield on soils low in available P, which is a
      serious agricultural limitation worldwide.

PMID- 19587105
TI  - Statement by the Growth Hormone Research Society on the GH/IGF-I axis in
      extending health span.
AB  - Despite the fact that growth hormone (GH) has not been approved for antiaging
      purposes, its use for this indication is widespread and increasing. The Growth
      Hormone Research Society (GRS) convened an international workshop to critically
      review and debate the available evidence related to the use of GH in the older
      adults and the relationship between the GH/insulin-like growth factor I (IGF-I)
      axis and the aging process. This statement presents the conclusions reached and
      gives recommendations for future studies in this research field regarding the use
      of GH and growth hormone secretagogues (GHS) for promoting health span. The
      participants concluded that, until future clinical research in this area is
      conducted, in particular carefully designed, long-term studies, using validated
      outcome parameters, the clinical use of GH or GHS in older adults, alone or in
      combination with testosterone, cannot be recommended. In addition, future basic
      studies in model systems, to continue to unravel GH/IGF-I effects related to
      human life span and health span, were advocated.

PMID- 19587104
TI  - Null mutation of the MdACS3 gene, coding for a ripening-specific 1
      aminocyclopropane-1-carboxylate synthase, leads to long shelf life in apple
      fruit.
AB  - Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase
      (ACS), parallels the level of ethylene production in ripening apple (Malus
      domestica) fruit. Here we show that expression of another ripening-specific ACS
      gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3
      weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases.
      Because MdACS3 expression continues in ripening fruit treated with 1
      methylcyclopropene, its transcription appears to be regulated by a negative
      feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated
      from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp
      transposon-like insertion in their 5' flanking region that may prevent
      transcription of these genes during ripening. A single nucleotide polymorphism in
      the coding region of MdACS3a results in an amino acid substitution (glycine-289 -
      > valine) in the active site that inactivates the enzyme. Furthermore, another
      null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found
      by DNA sequencing. Apple cultivars homozygous or heterozygous for both null
      allelotypes showed no or very low expression of ripening-related genes and
      maintained fruit firmness. These results suggest that MdACS3a plays a crucial
      role in regulation of fruit ripening in apple, and is a possible determinant of
      ethylene production and shelf life in apple fruit.

PMID- 19587106
TI  - Deceleration of senescence in normal human fibroblasts by withanone extracted
      from ashwagandha leaves.
AB  - Ashwagandha is an Ayurvedic shrub that forms a common ingredient of health
      supplements, tonics, and Indian home remedies designed to promote health and
      quality of life. Though sustained through experience and history, there are only
      a limited laboratory studies and experimental evidence to its effects. In our
      efforts to characterize Ashwagandha activities and their molecular mechanisms, we
      initially prepared leaf extract of Ashwagandha (i-Extract) that showed tumor
      inhibitory activity. In the present study, we demonstrate that a major component
      of i-Extract and withanone (i-Factor) protected the normal human fibroblasts
      against the toxicity caused by withaferin A. It increased the in vitro division
      potential of normal human cells that appeared to be mediated by decreased
      accumulation of molecular damage, downregulation of the senescence-specific beta
      galactosidase activity and the senescence marker protein, p21(WAF-1), protection
      against oxidative damage, and induction of proteasomal activity. To the best of
      our knowledge, we provide the first example of phytochemical(s) (i-Extract and
      withanone) that have both anticancer and antiaging activities and point to the
      molecular link between aging and cancer.

PMID- 19587107
TI  - Accelerated features of age-related bone loss in zmpste24 metalloproteinase
      deficient mice.
AB  - Age-related bone loss is associated with changes in bone cellularity, which
      include marrow fat infiltration and decreasing levels of osteoblastogenesis. The
      mechanisms that explain these changes remain unclear. Although nuclear lamina
      alterations occur in premature aging syndromes that include changes in body fat
      and severe osteoporosis, the role of proteins of the nuclear lamina in age
      related bone loss remains unknown. Using the Zmpste24-null progeroid mice
      (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed
      prelamin A, we identified several alterations in bone cellularity in vivo. We
      found that defective prelamin A processing induced accelerated features of age
      related bone loss including lower osteoblast and osteocyte numbers and higher
      levels of marrow adipogenesis. In summary, processing of prelamin A could become
      a new approach to regulate osteoblastogenesis and bone turnover and thus for the
      prevention and treatment of senile osteoporosis.

PMID- 19587109
TI  - Patient satisfaction, empowerment, and health and disability status effects of a
      disease management-health promotion nurse intervention among Medicare
      beneficiaries with disabilities.
AB  - PURPOSE: To report the impact on patient and informal caregiver satisfaction,
      patient empowerment, and health and disability status of a primary care
      affiliated disease self-management-health promotion nurse intervention for
      Medicare beneficiaries with disabilities and recent significant health services
      use. DESIGN AND METHODS: The Medicare Primary and Consumer-Directed Care
      Demonstration was a 24-month randomized controlled trial that included a nurse
      intervention. The present study (N = 766) compares the nurse (n = 382) and
      control (n = 384) groups. Generalized linear models for repeated measures, linear
      regression, and ordered logit regression were used. RESULTS: The patients whose
      activities of daily living (ADL) were reported by the same respondent at baseline
      and 22 months following baseline had significantly fewer dependencies at 22
      months than did the control group (p = .038). This constituted the vast majority
      of respondents. In addition, patient satisfaction significantly improved for 6 of
      7 domains, whereas caregiver satisfaction improved for 2 of 8 domains. However,
      the intervention had no effect on empowerment, self-rated health, the SF-36
      physical and mental health summary scores, and the number of dependencies in
      instrumental ADL. IMPLICATION: If confirmed in other studies, this intervention
      holds the potential to reduce the rate of functional decline and improve
      satisfaction for Medicare beneficiaries with ADL dependence.

PMID- 19587108
TI  - Use of pressure-redistributing support surfaces among elderly hip fracture
      patients across the continuum of care: adherence to pressure ulcer prevention
      guidelines.
AB  - PURPOSE: To estimate the frequency of use of pressure-redistributing support
      surfaces (PRSS) among hip fracture patients and to determine whether higher
      pressure ulcer risk is associated with greater PRSS use. DESIGN AND METHODS:
      Patients (n = 658) aged >or=65 years who had surgery for hip fracture were
      examined by research nurses at baseline and on alternating days for 21 days.
      Information on PRSS use and pressure ulcer risk factors was recorded at each
      assessment visit. Other information was obtained by interview and chart review.
      RESULTS: A PRSS was observed at 36.4% of the 5,940 study visits. The odds of PRSS
      use were lower in the rehabilitation setting (adjusted odds ratio [OR] 0.4, 95%
      confidence interval [CI] 0.3-0.6), in the nursing home (adjusted OR 0.2, 95% CI
      0.1-0.3), and during readmission to the acute setting (adjusted OR 0.6, 95% CI
      0.4-0.9) than in the initial acute setting. There was wide variation in frequency
      of PRSS use by admission hospital, even after adjusting for pressure ulcer risk
      factors. The relationships between PRSS use and pressure ulcer risk factors were
      not strong. IMPLICATIONS: In this study of hip fracture patients, adherence to
      guidelines for PRSS use was low and was based more on facility-related factors
      than on patient risk. There is an urgent need for health care providers to
      improve strategies for the prevention of pressure ulcers in high-risk patients.

PMID- 19587110
TI  - Age-dependent regression analysis of male gonadal axis.
AB  - The mechanisms by which aging progressively depletes testosterone (Te)
      availability in the male are unknown. Accordingly, the objective was to estimate
      brain gonadotropin-releasing hormone (GnRH) outflow (release and action), which
      cannot be observed directly, on the basis of downstream effects on pituitary
      luteinizing hormone (LH) secretion. LH, in turn, feeds forward on (stimulates)
      gonadal Te secretion, which then feeds back on (inhibits) GnRH-driven LH
      secretion. LH and Te concentrations were measured repetitively (every 10 min)
      over 18 h during graded pharmacological blockade of endogenous GnRH outflow in 24
      healthy 20- to 72-yr-old men. Data were analyzed using a new age-dependent
      regression model of GnRH-LH-Te interactions to estimate pulsatile LH secretion
      and elimination, GnRH outflow, LH feedforward, and Te feedback. By incorporating
      regression on age within the dose-response model, we show that aging erodes all
      three primary forward and reverse pathways linking the brain, pituitary gland,
      and testes. Aging is associated with concomitant deficits in GnRH --> LH
      feedforward, LH --> Te feedforward, and Te --> GnRH/LH feedback. The analytical
      formalism should be generalizable to other ensemble regulatory systems, such as
      those that control growth, reproduction, stress adaptations, and glucose
      metabolism.

PMID- 19587111
TI  - Endogenous angiotensin II facilitates GABAergic neurotransmission afferent to the
      Na+-responsive neurons of the rat median preoptic nucleus.
AB  - The median preoptic nucleus (MnPO) is densely innervated by efferent projections
      from the subfornical organ (SFO) and, therefore, is an important relay for the
      peripheral chemosensory and humoral information (osmolality and serum levels ANG
      II). In this context, controlling the excitability of MnPO neuronal populations
      is a major determinant of body fluid homeostasis and cardiovascular regulation.
      Using a brain slice preparation and patch-clamp recordings, our study sought to
      determine whether endogenous ANG II modulates the strength of the SFO-derived
      GABAergic inputs to the MnPO. Our results showed that the amplitude of the
      inhibitory postsynaptic currents (IPSCs) were progressively reduced by 44 +/-
      2.3% by (Sar(1), Ile(8))-ANG II, a competitive ANG type 1 receptor (AT(1)R)
      antagonist. Similarly, losartan, a nonpeptidergic AT(1)R antagonist decreased the
      IPSC amplitude by 40.4 +/- 5.6%. The facilitating effect of endogenous ANG II on
      the GABAergic input to the MnPO was not attributed to a change in GABA release
      probability and was mimicked by exogenous ANG II, which potentiated the amplitude
      of the muscimol-activated GABA(A)/Cl(-) current by 53.1 +/- 11.4%. These results
      demonstrate a postsynaptic locus of action of ANG II. Further analysis reveals
      that ANG II did not affect the reversal potential of the synaptic inhibitory
      response, thus privileging a cross talk between postsynaptic AT(1) and GABA(A)
      receptors. Interestingly, facilitation of GABAergic neurotransmission by
      endogenous ANG II was specific to neurons responding to changes in the ambient
      Na(+) level. This finding, combined with the ANG II-mediated depolarization of
      non-Na(+)-responsive neurons reveals the dual actions of ANG II to modulate the
      excitability of MnPO neurons.

PMID- 19587112
TI  - The effect of muscle phospholipid fatty acid composition on exercise performance:
      a direct test in the migratory white-throated sparrow (Zonotrichia albicollis).
AB  - Dietary polyunsaturated fatty acids (PUFA) can have various effects on animal
      physiology through their roles as energy, structural, regulatory, and signaling
      molecules. Of recent interest has been the incorporation of dietary PUFA into
      muscle membranes as phospholipids, thereby potentially affecting exercise
      performance by mechanisms such as altered mitochondrial proton leak and membrane
      bound protein activity. We first studied the effects of a high-omega6 PUFA diet
      vs. a high-omega3 PUFA diet on peak metabolic rate (PMR) in white-throated
      sparrows, and additionally measured mRNA expression of fatty acid transporters
      and the activity of major oxidative enzymes. Our experiment, thus, allowed a test
      of the "natural doping" hypothesis. With a simple diet manipulation, the two
      groups of sparrows diverged significantly in both muscle phospholipid composition
      and adipose triacylglycerol composition. The high-omega6 sparrows achieved higher
      PMR without a change in enzyme activity or transporter expression. We then fed
      sparrows the 2 diets, followed by a food restriction (H omega3RI and H omega6RI
      treatments). When their adipose stores were exhausted, we fed both groups a
      common diet of intermediate fatty acid composition. This protocol resulted in the
      H omega6RI and H omega3RI groups diverging significantly in muscle phospholipid
      composition, but they had substantially similar adipose stores. PMR did not
      differ between the H omega6RI and H omega3RI groups. We conclude that muscle
      phospholipids do not play a major role in affecting exercise performance. The
      fatty acid composition of stored triacylglycerol may instead affect exercise via
      the preferential use of particular fatty acids by muscles.

PMID- 19587113
TI  - Correlation of cardiac performance with cellular energetic components in the
      oxygen-deprived turtle heart.
AB  - The relationship between cardiac energy metabolism and the depression of
      myocardial performance during oxygen deprivation has remained enigmatic. Here, we
      combine in vivo (31)P-NMR spectroscopy and MRI to provide the first temporal
      profile of in vivo cardiac energetics and cardiac performance of an anoxia
      tolerant vertebrate, the freshwater turtle (Trachemys scripta) during long-term
      anoxia exposure (approximately 3 h at 21 degrees C and 11 days at 5 degrees C).
      During anoxia, phosphocreatine (PCr), unbound levels of inorganic phosphate
      (effective P(i)(2-)), intracellular pH (pH(i)), and free energy of ATP hydrolysis
      (dG/dxi) exhibited asymptotic patterns of change, indicating that turtle
      myocardial high-energy phosphate metabolism and energetic state are reset to new,
      reduced steady states during long-term anoxia exposure. At 21 degrees C, anoxia
      caused a reduction in pH(i) from 7.40 to 7.01, a 69% decrease in PCr and a
      doubling of effective P(i)(2-). ATP content remained unchanged, but the free
      energy of ATP hydrolysis (dG/dxi) decreased from -59.6 to -52.5 kJ/mol. Even so,
      none of these cellular changes correlated with the anoxic depression of cardiac
      performance, suggesting that autonomic cardiac regulation may override putative
      cellular feedback mechanisms. In contrast, during anoxia at 5 degrees C, when
      autonomic cardiac control is severely blunted, the decrease of pH(i) from 7.66 to
      7.12, 1.9-fold increase of effective P(i)(2-), and 6.4 kJ/mol decrease of dG/dxi
      from -53.8 to -47.4 kJ/mol were significantly correlated to the anoxic depression
      of cardiac performance. Our results provide the first evidence for a close, long
      term coordination of functional cardiac changes with cellular energy status in a
      vertebrate, with a potential for autonomic control to override these immediate
      relationships.

PMID- 19587114
TI  - Regular exercise attenuates the metabolic drive to regain weight after long-term
      weight loss.
AB  - Weight loss is accompanied by several metabolic adaptations that work together to
      promote rapid, efficient regain. We employed a rodent model of regain to examine
      the effects of a regular bout of treadmill exercise on these adaptations. Obesity
      was induced in obesity-prone rats with 16 wk of high-fat feeding and limited
      physical activity. Obese rats were then weight reduced (approximately 14% of body
      wt) with a calorie-restricted, low-fat diet and maintained at that reduced weight
      for 8 wk by providing limited provisions of the diet with (EX) or without (SED) a
      daily bout of treadmill exercise (15 m/min, 30 min/day, 6 days/wk). Weight
      regain, energy balance, fuel utilization, adipocyte cellularity, and humoral
      signals of adiposity were monitored during eight subsequent weeks of ad libitum
      feeding while the rats maintained their respective regimens of physical activity.
      Regular exercise decreased the rate of regain early in relapse and lowered the
      defended body weight. During weight maintenance, regular exercise reduced the
      biological drive to eat so that it came closer to matching the suppressed level
      of energy expenditure. The diurnal extremes in fuel preference observed in weight
      reduced rats were blunted, since exercise promoted the oxidation of fat during
      periods of feeding (dark cycle) and promoted the oxidation of carbohydrate (CHO)
      later in the day during periods of deprivation (light cycle) . At the end of
      relapse, exercise reestablished the homeostatic steady state between intake and
      expenditure to defend a lower body weight. Compared with SED rats, relapsed EX
      rats exhibited a reduced turnover of energy, a lower 24-h oxidation of CHO, fewer
      adipocytes in abdominal fat pads, and peripheral signals that overestimated their
      adiposity. These observations indicate that regimented exercise altered several
      metabolic adaptations to weight reduction in a manner that would coordinately
      attenuate the propensity to regain lost weight.

PMID- 19587115
TI  - Cardiovascular changes during daily torpor in the laboratory mouse.
AB  - The laboratory mouse is a facultative daily heterotherm in that it experiences
      bouts of torpor under caloric restriction. Mice are the most frequently studied
      laboratory mammal, and often, genetically modified mice are used to investigate
      many physiological functions related to weight loss and caloric intake. As such,
      research documenting the cardiovascular changes during fasting-induced torpor in
      mice is warranted. In the current study, C57BL/6 mice were implanted either with
      EKG/temperature telemeters or blood pressure telemeters. Upon fasting and
      exposure to an ambient temperature (T(a)) of 19 degrees C, mice entered torpor
      bouts as assessed by core body temperature (T(b)). Core T(b) fell from 36.6 +/-
      0.2 degrees C to a minimum of 25.9 +/- 0.9 degrees C during the fast, with a
      concomitant fall in heart rate from 607 +/- 12 beats per minute (bpm) to a
      minimum of 158 +/- 20 bpm. Below a core T(b) of 31 degrees C, heart rate fell
      exponentially with T(b), and the Q(10) was 2.61 +/- 0.18. Further, mice implanted
      with blood pressure telemeters exhibited similar heart rate and activity profiles
      as those implanted with EKG/temperature telemeters, and the fall in heart rate
      and core T(b) during entrance into torpor was paralleled by a fall in blood
      pressure. The minimum systolic, mean, and diastolic blood pressures of torpid
      mice were 62.3 +/- 10.2, 51.9 +/- 9.2, 41.0 +/- 7.5 mmHg, respectively. Torpid
      mice had a significantly lower heart rate (25-35%) than when euthermic at mean
      arterial pressures from 75 to 100 mmHg, suggesting that total peripheral
      resistance is elevated during torpor. These data provide new and significant
      insight into the cardiovascular adjustments that occur in torpid mice.

PMID- 19587117
TI  - The class II phosphatidylinositol 3 kinase C2beta is required for the activation
      of the K+ channel KCa3.1 and CD4 T-cells.
AB  - The Ca(2+)-activated K(+) channel KCa3.1 is required for Ca(2+) influx and the
      subsequent activation of T-cells. We previously showed that nucleoside
      diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, directly
      phosphorylates and activates KCa3.1 and is required for the activation of human
      CD4 T lymphocytes. We now show that the class II phosphatidylinositol 3 kinase
      C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and functions
      upstream of NDPK-B to activate KCa3.1 channel activity. Decreased expression of
      PI3K-C2beta by siRNA in human CD4 T-cells resulted in inhibition of KCa3.1
      channel activity. The inhibition was due to decreased phosphatidylinositol 3
      phosphate [PI(3)P] because dialyzing PI3K-C2beta siRNA-treated T-cells with
      PI(3)P rescued KCa3.1 channel activity. Moreover, overexpression of PI3K-C2beta
      in KCa3.1-transfected Jurkat T-cells led to increased TCR-stimulated activation
      of KCa3.1 and Ca(2+) influx, whereas silencing of PI3K-C2beta inhibited both
      responses. Using total internal reflection fluorescence microscopy and planar
      lipid bilayers, we found that PI3K-C2beta colocalized with Zap70 and the TCR in
      peripheral microclusters in the immunological synapse. This is the first
      demonstration that a class II PI3K plays a critical role in T-cell activation.

PMID- 19587118
TI  - Central role of the oxygen-dependent degradation domain of Drosophila
      HIFalpha/Sima in oxygen-dependent nuclear export.
AB  - The Drosophila HIFalpha homologue, Sima, is localized mainly in the cytoplasm in
      normoxia and accumulates in the nucleus upon hypoxic exposure. We have
      characterized the mechanism governing Sima oxygen-dependent subcellular
      localization and found that Sima shuttles continuously between the nucleus and
      the cytoplasm. We have previously shown that nuclear import depends on an
      atypical bipartite nuclear localization signal mapping next to the C-terminus of
      the protein. We show here that nuclear export is mediated in part by a CRM1
      dependent nuclear export signal localized in the oxygen-dependent degradation
      domain (ODDD). CRM1-dependent nuclear export requires both oxygen-dependent
      hydroxylation of a specific prolyl residue (Pro850) in the ODDD, and the activity
      of the von Hippel Lindau tumor suppressor factor. At high oxygen tension rapid
      nuclear export of Sima occurs, whereas in hypoxia, Sima nuclear export is largely
      inhibited. HIFalpha/Sima nucleo-cytoplasmic localization is the result of a
      dynamic equilibrium between nuclear import and nuclear export, and nuclear export
      is modulated by oxygen tension.

PMID- 19587119
TI  - Divergent S phase checkpoint activation arising from prereplicative complex
      deficiency controls cell survival.
AB  - The DNA replication machinery plays additional roles in S phase checkpoint
      control, although the identities of the replication proteins involved in
      checkpoint activation remain elusive. Here, we report that depletion of the
      prereplicative complex (pre-RC) protein Cdc6 causes human nontransformed diploid
      cells to arrest nonlethally in G1-G1/S and S phase, whereas multiple cancer cell
      lines undergo G1-G1/S arrest and cell death. These divergent phenotypes are
      dependent on the activation, or lack thereof, of an ataxia telangiectasia and
      Rad3-related (ATR)-dependent S phase checkpoint that inhibits replication fork
      progression. Although pre-RC deficiency induces chromatin structural alterations
      in both nontransformed and cancer cells that normally lead to ATR checkpoint
      activation, the sensor mechanisms in cancer cells seem to be compromised such
      that higher levels of DNA replication stress/damage are required to trigger
      checkpoint response. Our results suggest that therapy-induced disruption of pre
      RC function might exert selective cytotoxic effects on tumor cells in human
      patients.

PMID- 19587120
TI  - Annexin A2 regulates phagocytosis of photoreceptor outer segments in the mouse
      retina.
AB  - The daily phagocytosis of shed photoreceptor outer segments by pigment epithelial
      cells is critical for the maintenance of the retina. In a subtractive polymerase
      chain reaction analysis, we found that functional differentiation of human ARPE19
      retinal pigment epithelial (RPE) cells is accompanied by up-regulation of annexin
      (anx) A2, a major Src substrate and regulator of membrane-cytoskeleton dynamics.
      Here, we show that anx A2 is recruited to the nascent phagocytic cup in vitro and
      in vivo and that it fully dissociates once the phagosome is internalized. In
      ARPE19 cells depleted of anx A2 by using small interfering RNA and in ANX A2(-/-)
      mice the phagocytosis of outer segments was impaired, and in ANX A2(-/-) mice
      there was an accumulation of phagocytosed outer segments in the RPE apical
      processes, indicative of retarded phagosome transport. We show that anx A2 is
      tyrosine phosphorylated at the onset of phagocytosis and that the synchronized
      activation of focal adhesion kinase and c-Src is abnormal in ANX A2(-/-) mice.
      These findings reveal that anx A2 is involved in the circadian regulation of
      outer segment phagocytosis, and they provide new insight into the protein
      machinery that regulates phagocytic function in RPE cells.

PMID- 19587121
TI  - A distinct mechanism to achieve efficient signal recognition particle (SRP)-SRP
      receptor interaction by the chloroplast srp pathway.
AB  - Cotranslational protein targeting by the signal recognition particle (SRP)
      requires the SRP RNA, which accelerates the interaction between the SRP and SRP
      receptor 200-fold. This otherwise universally conserved SRP RNA is missing in the
      chloroplast SRP (cpSRP) pathway. Instead, the cpSRP and cpSRP receptor (cpFtsY)
      by themselves can interact 200-fold faster than their bacterial homologues. Here,
      cross-complementation analyses revealed the molecular origin underlying their
      efficient interaction. We found that cpFtsY is 5- to 10-fold more efficient than
      Escherichia coli FtsY at interacting with the GTPase domain of SRP from both
      chloroplast and bacteria, suggesting that cpFtsY is preorganized into a
      conformation more conducive to complex formation. Furthermore, the cargo-binding
      M-domain of cpSRP provides an additional 100-fold acceleration for the
      interaction between the chloroplast GTPases, functionally mimicking the effect of
      the SRP RNA in the cotranslational targeting pathway. The stimulatory effect of
      the SRP RNA or the M-domain of cpSRP is specific to the homologous SRP receptor
      in each pathway. These results strongly suggest that the M-domain of SRP actively
      communicates with the SRP and SR GTPases and that the cytosolic and chloroplast
      SRP pathways have evolved distinct molecular mechanisms (RNA vs. protein) to
      mediate this communication.

PMID- 19587122
TI  - Rapeseed protein in a high-fat mixed meal alleviates postprandial systemic and
      vascular oxidative stress and prevents vascular endothelial dysfunction in
      healthy rats.
AB  - High-saturated fat and high-sucrose meals induce vascular endothelial
      dysfunction, the early hallmark of atherogenesis. The impact of dietary protein
      on vascular homeostasis remains misunderstood. In this study, we investigated
      whether rapeseed protein, an emergent arginine- and cysteine-rich protein, can
      acutely modulate the onset of adverse effects induced by a high-saturated fat
      meal (HFM). In a series of crossover experiments, healthy rats received 3 HFM
      (saturated fat: 60%; sucrose: 20%; protein: 20% energy) with the protein source
      being either total milk protein (MP; control), rapeseed protein (RP), or MP
      supplemented with cysteine and arginine to the same level as in RP (MP+AA).
      Endothelium-related vascular reactivity, measured as an acetylcholine-induced
      transient decrease in blood pressure, and plasma triglycerides, hydroperoxides,
      cyclic GMP (cGMP), and free 3-nitrotyrosine were measured before and 2, 4, and 6
      h after meals. Superoxide anion production, expressed as ethidine fluorescence,
      was measured in the aorta 6 h after meals. Whereas plasma triglycerides rose
      similarly in all meals, the decrease in vascular reactivity after MP was
      attenuated after MP+AA and entirely prevented after RP. The type of meal had no
      consistent effect on plasma cGMP and free 3-nitrotyrosine over the postprandial
      period. The postprandial increase in plasma hydroperoxides differed according to
      the meal, and concentrations were 43% lower 6 h after MP+AA and RP than after MP.
      Aortic superoxide anion production was 36% lower 6 h after RP than MP. These
      results show that substituting rapeseed protein for milk protein markedly reduces
      vascular and oxidative disturbances induced by an HFM and this may be mediated in
      part by cysteine and arginine.

PMID- 19587123
TI  - Carbohydrate restriction, as a first-line dietary intervention, effectively
      reduces biomarkers of metabolic syndrome in Emirati adults.
AB  - The prevalence of diabetes mellitus (DM) in the United Arab Emirates is among the
      highest world-wide. Metabolic syndrome (MetS) predisposes individuals to DM;
      therefore, dietary interventions targeting MetS biomarkers are a high priority.
      We evaluated whether a carbohydrate-restricted diet (CRD) could effectively be
      used as a first-line therapy intervention in adult Emirati to improve the
      characteristics of MetS. A total of 39 participants (14 men, 25 women) 18-50 y,
      classified with MetS, followed a CRD (20-25% carbohydrate, 50-55% fat, 25-30%
      protein energy distribution). After 6 wk, 19 participants were randomly switched
      to the AHA diet (55% carbohydrate, 25-30% fat, 15-20% protein) whereas 20
      participants continued with the CRD diet for an additional 6 wk. Fasting plasma
      lipids, 24-h dietary recalls, body composition, anthropometrics, blood pressure
      (BP), glucose, insulin, and plasma markers of inflammation were measured at
      baseline, wk 6, and wk 12. Dietary analysis indicated high compliance. At wk 6,
      the CRD (n = 39) resulted in decreased body weight (-13%), waist circumference (
      4.5%), body fat (-10.6%), and plasma triglycerides (TG) (-38.7%) (P < 0.001).
      Significant decreases in LDL cholesterol, BP, glucose, insulin, and inflammatory
      markers and increases in adiponectin (P < 0.05) also occurred. After 12 wk,
      positive changes persisted for all participants, independent of diet. However,
      body weight and plasma TG and insulin were lower in the CRD (P < 0.05) group than
      in the CRD + AHA group. Results from this study suggest that a 6-wk CRD can
      effectively be used as a first-line diet therapy to rapidly improve features of
      MetS and cardiovascular risk in adult Emirati.

PMID- 19587124
TI  - A responsive feeding intervention increases children's self-feeding and maternal
      responsiveness but not weight gain.
AB  - Responsive complementary feeding, whereby the mother feeds her child in response
      to child cues and psychomotor abilities, is low 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 6-session educational program that emphasized the
      practice of child self-feeding and maternal responsiveness. A total of 108
      mothers and their 8- to 20-mo-old children in 19 clusters were randomly assigned
      to the intervention group and 95 in 18 clusters were assigned to the
      informational control group. Outcomes were assessed at pretest, postintervention,
      and follow-up. Research assistants, who were unaware of group assignment,
      observed and coded mother and child midday meal behaviors. At follow-up, the
      percent of self-fed mouthfuls was 47.8 +/- 42.4 (mean +/- SD) in the responsive
      feeding group children compared with 32.2 +/- 41.0 in the controls (P = 0.01);
      likewise, the number of responsive verbalizations was 6.55 +/- 5.9 in the
      responsive feeding mothers and 4.62 +/- 4.5 in controls (P = 0.01). Intervention
      mothers recalled more messages. Mouthfuls of food eaten by children and weight
      were equivalent in the 2 groups. Lack of change in foods eaten and small
      quantities may explain the similarly low levels of weight gain. These results
      provide evidence that self-feeding and maternal verbal responsiveness, two
      developmentally important behaviors, can be increased by targeting specific
      behaviors with appropriate behavior change strategies of modeling and coached
      practice. Weight gain may require more nutritional input, especially in areas of
      high food insecurity.

PMID- 19587125
TI  - Provision of a school snack is associated with vitamin B-12 status, linear
      growth, and morbidity in children from Bogota, Colombia.
AB  - In 2004, Bogota's Secretary of Education (SED) initiated a snack program in
      public primary schools. A midmorning food ration was provided free of charge to
      children to supplement 30 and 50% of their daily requirements of energy and iron,
      respectively. The purpose of this study, an observational investigation of 3202
      children ages 5-12 y, was to examine whether the snack program improved
      children's nutritional and health status. We measured micronutrient levels
      (plasma ferritin and vitamin B-12, and erythrocyte folate), anthropometry, and
      reported morbidity during the first semester of the 2006 school year. After
      adjusting for socioeconomic status and other school interventions, children at
      schools receiving the snack (n = 1803) had greater increases in plasma vitamin B
      12 (42 pmol/L; P < 0.0001) from baseline to 3 mo of follow-up than children at
      schools not receiving the snack (n = 1399). They also experienced a smaller
      decrease in height-for-age Z-scores than children who did not receive the snack
      (P = 0.001). Provision of the SED snack was associated with significantly fewer
      reported days with morbidity symptoms (e.g. cough with fever, diarrhea with
      vomiting), 44% fewer doctor visits (P = 0.02), and 23% fewer days of school
      absenteeism (P = 0.03). The snack was not related to ferritin or folate levels.
      In conclusion, provision of a school-administered snack was related to improved
      vitamin B-12 status and linear growth and decreased reported morbidity. Although
      provision of the snack was not related to BMI changes over a 4-mo period, snack
      components such as candy and sugar-sweetened beverages should be replaced with
      healthier options, as the rates of child overweight in Colombia are not
      negligible.

PMID- 19587127
TI  - Slcyt, a newly identified sex-linked gene, has recently moved onto the X
      chromosome in Silene latifolia (Caryophyllaceae).
AB  - The sex chromosomes of the plant species Silene latifolia (white campion) are
      very young (only 5-10 My old), and all 11 X-linked genes so far described have Y
      linked homologues. Theory predicts that X chromosomes should accumulate a
      nonrandom set of genes. However, little is known about the importance of gene
      movements between the X and the autosomes in plants, or in any very young sex
      chromosome system. Here, we isolate from cDNA a new gene, Slcyt, on the S.
      latifolia X, which encodes a cytochrome B protein. We genetically mapped SlCyt
      and found that it is located approximately 1 cM from the pseudoautosomal region.
      Genes in this region of the X chromosome have low divergence values from their
      homologous Y-linked genes, indicating that the X only recently stopped
      recombining with the Y. Genetic mapping in Silene vulgaris suggests that Slcyt
      originally belonged to a different linkage group from that of the other S.
      latifolia X-linked genes. Silene latifolia has no Y-linked homologue of Slcyt,
      and also no autosomal paralogues seem to exist. Slcyt moved from an autosome to
      the X very recently, as the Cyt gene is also X linked in Silene dioica, the
      sister species to S. latifolia, but is probably autosomal in Silene diclinis,
      implying that a translocation to the X probably occurred after the split between
      S. diclinis and S. latifolia/S. dioica. Diversity at Slcyt is extremely low
      (pi(syn) = 0.16%), and we find an excess of high frequency-derived variants and a
      negative Tajima's D, suggesting that the translocation was driven by selection.

PMID- 19587128
TI  - Genomewide association between insertions/deletions and the nucleotide diversity
      in bacteria.
AB  - Spontaneous mutations are not randomly distributed throughout a genome. Although
      mutation hotspots are found on genomes of a variety of species, mechanisms that
      generate the hotspots are not well understood. In eukaryotes, strong association
      between a regional nucleotide substitution rate and insertions/deletions (indels)
      was reported in a previous study, and the "indel-induced mutation" hypothesis was
      proposed. However, it is unknown whether the association exists even in
      prokaryote genomes. In this study, we conducted a systematic survey for the
      association in 262 complete genomes from 73 bacterial species. In these bacteria,
      the level of nucleotide diversity was negatively correlated with the distance
      from the closest indel, which is consistent with the eukaryote data. The same
      pattern was observed even after excluding noncoding sequences, indicating that
      the difference in functional constraints among genomic regions is not a primary
      cause of the correlation. In addition, the increase of nucleotide substitution
      rate was detected disproportionally on a lineage carrying a derived indel
      mutation, confirming the indel-nucleotide diversity association in the bacterial
      genomes. In some cases, the level of nucleotide diversity was more than 100 times
      higher in regions close to indels than in distant regions. Although further
      understanding of the molecular mechanism is required to test the hypothesis,
      these results suggest that the same mechanism for the indel-nucleotide diversity
      associations might exist in eukaryotes and prokaryotes and play an important role
      in molecular evolution.

PMID- 19587126
TI  - Women's Health Initiative diet intervention did not increase macular pigment
      optical density in an ancillary study of a subsample of the Women's Health
      Initiative.
AB  - In this study, we examined the impact of long-term (>8 y), low-fat, high-fruit
      and -vegetable diets on levels of lutein and zeaxanthin in the macula of the
      retina, as indicated by the OD of macular pigment. Macular pigment OD, measured
      by heterochromatic flicker photometry, was compared in women aged 60-87 y, who, 7
      18 mo earlier (median 12 mo), had been in the dietary modification intervention
      (n = 158) or comparison (n = 236) groups of the Women's Health Initiative (WHI)
      at the Madison, WI site for a mean of 8.5 y. Women in the intervention group ate
      more fruits and vegetables (mean +/- SEM) (6.1 +/- 0.2 vs. 4.6 +/- 0.2
      servings/d; P < 0.0001) and had higher intakes of lutein and zeaxanthin from
      foods and supplements (2.7 +/- 0.2 vs. 2.1 +/- 0.1 mg/d; P = 0.0003) than the
      comparison group. However, macular pigment density did not differ between the
      intervention (0.36 +/- 0.02 OD units) and comparison (0.35 +/- 0.01 OD units)
      groups. It tended to be higher (11%; P = 0.11) in women consuming lutein and
      zeaxanthin in the highest compared with the lowest quintile (median 6.4 vs. 1.1
      mg/d). The increase in fruit and vegetable intake among dietary modification
      participants of this WHI subsample was not of sufficient magnitude to alter the
      mean density of retinal carotenoids, given other existing dietary conditions in
      this sample.

PMID- 19587129
TI  - Symptoms and signs of syncope: a review of the link between physiology and
      clinical clues.
AB  - Detailed history taking is of paramount importance to establish a reliable
      diagnosis in patients with transient loss of consciousness. In this article the
      clinical symptoms and signs of the successive phases of a syncopal episode are
      reviewed. A failure of the systemic circulation to perfuse the brain sufficiently
      results in a stereotyped progression of neurological symptoms and signs
      culminating in loss of consciousness; when transient, this is syncope. Prior to
      loss of consciousness the affected individual tends to exhibit unclear thinking,
      followed by fixation of the eyes in the midline and a 'frozen' appearance.
      Narrowing of the field of vision with loss of colour vision ('greying' out) and
      finally a complete loss of vision (hence 'blacking' out) occurs. Hearing loss may
      occur following loss of vision. This process may take as little as approximately
      7 s in cases of sudden complete circulatory arrest (e.g. abrupt asystole), but in
      other circumstances it may take longer depending on the rate and depth of
      cerebral hypoperfusion. Complete loss of consciousness occurs with the 'turning
      up' of the eyeballs. Profound cerebral hypoperfusion may be accompanied by
      myoclonic jerks.

PMID- 19587130
TI  - Application of game theory to the interaction between plant viruses during mixed
      infections.
AB  - Natural mixed infections of plant viruses are frequent, often leading to
      unpredictable variations in symptoms, infectivity, accumulation and/or vector
      transmissibility. Cauliflower mosaic caulimovirus (CaMV) has often been found in
      mixed infections with turnip mosaic potyvirus (TuMV) in plants of the genus
      Brassica. This study addressed the effect of mixed infection on infectivity,
      pathogenicity and accumulation of CaMV and TuMV in Arabidopsis thaliana plants
      inoculated mechanically with cDNA infectious clones. In singly infected plants,
      TuMV accumulation was approximately 8-fold higher than that of CaMV. In co
      infected plants, there was 77 % more TuMV accumulation compared with single
      infections, whilst the accumulation of CaMV was 56 % lower. This outcome
      describes a biological game in which TuMV always plays the winner strategy,
      leading to the competitive exclusion of CaMV. However, the infectivity of each
      virus was not affected by the presence of the other, and no symptom synergism was
      observed.

PMID- 19587131
TI  - Smallpox vaccines induce antibodies to the immunomodulatory, secreted vaccinia
      virus complement control protein.
AB  - Vaccination with Dryvax elicits a broad humoral response against many viral
      proteins. Human vaccinia immune globulin was used to screen the secreted proteins
      from cells infected with Dryvax or the candidate smallpox vaccine LC16m8 to
      determine whether the protective humoral response included antibodies against
      secreted viral proteins. Many proteins were detected, with the primary band
      corresponding to a band of 28 or 30 kDa in cells infected with Dryvax or LC16m8,
      respectively. This was identified as the vaccinia virus complement protein (VCP),
      which migrated more slowly in LC16m8-infected cells due to post-translational
      glycosylation. Vaccinia virus deleted in VCP, vVCPko, protected mice from a
      lethal intranasal challenge of vaccinia Western Reserve strain. Mice vaccinated
      with purified VCP demonstrated a strong humoral response, but were not protected
      against a moderate lethal challenge of vaccinia virus, suggesting that the
      humoral response against VCP is not critical for protection.

PMID- 19587132
TI  - Identification of amino acids in the dengue virus type 2 envelope glycoprotein
      critical to virus infectivity.
AB  - The dengue virus envelope glycoprotein mediates virus attachment and entry and is
      the major viral antigen. The identification of 'critical' amino acids in the
      envelope glycoprotein that cannot be altered without loss of infectivity could
      have a major impact on the development of dengue virus vaccines and diagnostics.
      In this context, we determined whether six amino acids, previously predicted by
      computational analysis to play a critical role in the virus life cycle, were
      essential for virus viability. The effects of mutating the six 'critical' amino
      acids and a further seven 'neutral' amino acids were analysed by using a dengue
      virus type 2 infectious cDNA clone. Of the six critical amino acids, three (Asp
      215, Pro-217 and His-244) were found to be essential for virus viability in
      mammalian and mosquito cells.

PMID- 19587133
TI  - Protective effect of the T112 PrP variant in sheep challenged with bovine
      spongiform encephalopathy.
AB  - Sheep with an ARQ/ARQ PRNP genotype at codon positions 136/154/171 are highly
      susceptible to experimental infection with bovine spongiform encephalopathy
      (BSE). However, a number of sheep challenged orally or intracerebrally with BSE
      were clinically asymptomatic and found to survive or were diagnosed as BSE
      negative when culled. Sequencing of the full PRNP gene open reading frame of BSE
      susceptible and -resistant sheep indicated that, in the majority of Suffolk
      sheep, resistance was associated with an M112T PRNP variant (TARQ allele). A high
      proportion (47 of 49; 96%) of BSE-challenged wild-type (MARQ/MARQ) Suffolk sheep
      were BSE-infected, whereas none of the 20 sheep with at least one TARQ allele
      succumbed to BSE. Thirteen TARQ-carrying sheep challenged with BSE are still
      alive and some have survival periods equivalent to, or greater than, reported
      incubation periods of BSE in ARR/ARR and VRQ/VRQ sheep.

PMID- 19587135
TI  - Assembly of monomeric human cytomegalovirus pUL104 into portal structures.
AB  - In order for human cytomegalovirus (HCMV) to replicate, concatemeric DNA has to
      be cleaved into unit-length genomes and packaged into preformed capsids. For
      packaging to take place and DNA to be translocated, a channel is required in the
      capsid. Viral capsid channels are generally formed by portal proteins. Here, we
      show by cross-linking, native gel electrophoresis of infected cells and gel
      permeation chromatography that the HCMV portal candidate protein pUL104 can form
      dimers and higher order multimers. Electron microscopy of purified monomeric
      pUL104 after 5 min incubation revealed that the protein had assembled into a
      multimeric form and that this form closely resembles complete portal assembly.
      This is the first study to show that pUL104 monomers have the ability to form
      portal complexes without additional viral proteins.

PMID- 19587134
TI  - Bovine leukemia virus can be classified into seven genotypes: evidence for the
      existence of two novel clades.
AB  - Previous studies have classified the env sequences of bovine leukemia virus (BLV)
      provirus from different locations worldwide into between two and four genetic
      groupings. These different studies gave unique names to the identified groups and
      no study has yet integrated all the available sequences. Thus, we hypothesized
      that many of the different groups previously identified actually correspond to a
      limited group of genotypes that are unevenly distributed worldwide. To examine
      this hypothesis, we sequenced the env gene from 28 BLV field strains and compared
      these sequences to 46 env sequences that represent all the genetic groupings
      already identified. By using phylogenetic analyses, we recovered six clades, or
      genotypes, that we have called genotypes 1, 2, 3, 4, 5 and 6. Genotypes 1-5 have
      counterparts among the sequence groupings identified previously. One env sequence
      did not cluster with any of the others and was highly divergent when compared
      with the six genotypes identified here. Thus, an extra genotype, which we named
      7, may exist. Similarity comparisons were highly congruent with phylogenetic
      analyses. Furthermore, our analyses confirmed the existence of geographical
      clusters.

PMID- 19587136
TI  - Molecular characterization of full-length genomic segment 2 of a bovine
      picobirnavirus (PBV) strain: evidence for high genetic diversity with genogroup I
      PBVs.
AB  - We report here the molecular characterization of a bovine genogroup I
      picobirnavirus strain RUBV-P detected from a 1-month-old diarrhoeic calf in
      eastern India. Sequence comparisons and phylogenetic analysis of a short stretch
      of gene segment 2 of RUBV-P revealed low nucleotide identities (51.2-64.9%) with
      and distant genetic relatedness to other genogroup I picobirnaviruses. The
      complete gene segment 2 sequence of RUBV-P was obtained by the single primer
      amplification method with modifications. Gene segment 2 of RUBV-P was 1758 bp
      long, encoded a predicted protein of 554 aa and exhibited low nucleotide (58.1
      58.8%) and amino acid (51.3-55.4%) identities with genogroup I human strains
      Hy005102 and 1-CHN-97. The 5'- and 3'-end nucleotide sequences, and the three
      motifs of RNA-dependent RNA polymerases of double-stranded RNA viruses, were
      conserved among these strains. Our findings suggested that bovine strain RUBV-P
      might be distinct from genogroup I picobirnaviruses of humans and other animals.

PMID- 19587137
TI  - Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm,
      SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and
      identification of novel T-cell epitopes in mice via codon optimization.
AB  - As a prelude to primate studies, the immunogenicity of wild-type and codon
      optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and
      without co-administered granulocyte-macrophage colony-stimulating factor (GM-CSF)
      DNA, was directly compared in two strains of mice. Gag-specific T cells in the
      splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by
      ELISpot using panels of overlapping synthetic peptides (15mers) spanning the
      entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1.
      Specific antibodies were measured by ELISA. Codon optimization was shown to
      significantly increase the immune response to the DNA immunogens, reducing the
      amount of DNA necessary to induce cellular and antibody responses by one and two
      orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was
      necessary for the induction of high level T- and B-cell responses. Finally, it
      was possible to identify both known and novel T-cell epitopes in the Gag proteins
      of the three viruses.

PMID- 19587138
TI  - Characterization of the herpes simplex virus (HSV)-1 tegument protein VP1-2
      during infection with the HSV temperature-sensitive mutant tsB7.
AB  - VP1-2, encoded by the UL36 gene of herpes simplex virus (HSV), is a large
      structural protein, conserved across the family Herpesviridae, that is assembled
      into the tegument and is essential for virus replication. Current evidence
      indicates that VP1-2 is a central component in the tegumentation and envelopment
      processes and that it also possesses important roles in capsid transport and
      entry. However, any detailed mechanistic understanding of VP1-2 function(s)
      remains limited. This study characterized the replication of HSV-1 tsB7, a
      temperature-sensitive mutant restricted at the non-permissive temperature due to
      a defect in VP1-2 function. A tsB7 virus expressing green fluorescent protein
      fused VP16 protein was used to track the accumulation and location of a major
      tegument protein. After infection at the permissive temperature and shift to the
      non-permissive temperature, the production of infectious virus ceased. VP1-2
      accumulated in altered cytosolic clusters, together with VP16 and other virion
      proteins. Furthermore, correlating with the results of immunofluorescence,
      electron microscopy demonstrated abnormal cytosolic capsid clustering and a block
      in envelopment. As VP1-2 encompasses a ubiquitin-specific protease domain, the
      occurrence of ubiquitin-conjugated proteins during tsB7 infection was also
      examined at the non-permissive temperature. A striking overaccumulation was
      observed of ubiquitin-specific conjugates in cytoplasmic clusters, overlapping
      and adjacent to the VP1-2 clusters. These results are discussed in relation to
      the possible functions of VP1-2 in the assembly pathway and the nature of the
      defect in tsB7.

PMID- 19587140
TI  - Low pH stimulates vasopressin V2 receptor promoter activity and enhances
      downregulation induced by V1a receptor stimulation.
AB  - Arginine vasopressin (AVP) plays a key role in the urine concentration mechanism
      via the vasopressin V2 receptor (V2R) and aquaporin 2 (AQP2) in the kidney. It is
      well known that V2R is localized on the basolateral side and the V1a receptor
      (V1aR) is distributed on the luminal side of the collecting ducts. Previously, we
      reported an increase of V1aR mRNA and a decrease of V2R mRNA in the collecting
      ducts under chronic metabolic acidosis. However, the regulatory mechanism of V2R
      in acidic conditions has not yet been determined. In the present study, we
      investigated the effect of changes in pH on V2R promoter activity, using the LLC
      PK(1) cell line stably expressing rat V1aR (LLC-PK(1)/rV1aR). The rV2R promoter
      activity was significantly increased at 12 h after the incubation in low-pH
      conditions, which was sustained for 24 h. mRNA and protein expressions of V2R
      were also increased in low-pH conditions. V1aR stimulation suppressed rV2R
      promoter activity in a pH-dependent manner. PKA and JNK inhibitors suppressed
      rV2R promoter activity in both neutral and low-pH conditions without FBS.
      However, a JNK inhibitor prevented the increase of V2R promoter activity only in
      low-pH conditions in the presence of FBS. In summary, V2R expression is increased
      at transcriptional, mRNA, and protein levels in LLC-PK(1)/rV1aR cells under low
      pH conditions. Acidic condition-induced V2R enhancement was suppressed by V1aR
      stimulation, suggesting the crucial role of V1aR in water and electrolyte
      homeostasis in acidosis.

PMID- 19587139
TI  - Social stress in mice induces voiding dysfunction and bladder wall remodeling.
AB  - Several studies have anecdotally reported the occurrence of altered urinary
      voiding patterns in rodents exposed to social stress. A recent study
      characterized the urodynamic and central changes in a rat model of social defeat.
      Here, we describe a similar voiding phenotype induced in mice by social stress
      and in addition we describe potential molecular mechanisms underlying the
      resulting bladder wall remodeling. The mechanism leading to the altered voiding
      habits and underlying bladder phenotype may be relevant to the human syndrome of
      dysfunctional voiding which is thought to have a psychological component. To
      better characterize and investigate social stress-induced bladder wall
      hypertrophy, FVB mice (6 wk old) were randomized to either social stress or
      control manipulation. The stress involved repeated cycles of a 1-h direct
      exposure to a larger aggressive C57Bl6 breeder mouse followed by a 23-h period of
      barrier separation over 4 wk. Social stress resulted in altered urinary voiding
      patterns suggestive of urinary retention and increased bladder mass. In vivo
      cystometry revealed an increased volume at micturition with no change in the
      voiding pressure. Examination of these bladders revealed increased nuclear
      expression of the transcription factors MEF-2 and NFAT, as well as increased
      expression of the myosin heavy chain B isoform mRNA. BrdU uptake was increased
      within the urothelium and lamina propria layers in the social stress group. We
      conclude that social stress induces urinary retention that ultimately leads to
      shifts in transcription factors, alterations in myosin heavy chain isoform
      expression, and increases in DNA synthesis that mediate bladder wall remodeling.
      Social stress-induced bladder dysfunction in rodents may provide insight into the
      underlying mechanisms and potential treatment of dysfunctional voiding in humans.

PMID- 19587141
TI  - Characterization of the kinase activity of a WNK4 protein complex.
AB  - Mutations in WNK4 protein kinase cause pseudohypoaldosteronism type II (PHAII), a
      genetic disorder that is characterized by renal NaCl and K(+) retention leading
      to hypertension and hyperkalemia. Consistent with this, WNK4 is known to regulate
      several renal tubule transporters, including the NaCl cotransporter, NCC, and the
      K(+) channel, ROMK, but the mechanisms are incompletely understood, and the role
      of the kinase activity in its actions is highly controversial. To assay WNK4
      kinase activity, we have now succeeded in expressing and purifying full-length,
      enzymatically active WNK4 protein from HEK293 cells. We show that full-length
      wild-type WNK4 phosphorylates oxidative stress response kinase 1 (OSR1) and
      Ste20/SPS1-related proline/alanine-rich kinase (SPAK) in vitro. Introducing the
      PHAII-associated mutations, E559K, D561A, and Q562E, into our protein had no
      significant effect on this phosphorylation. We conclude that PHAII is unlikely to
      be caused by abnormal WNK4 kinase activity. We also made the intriguing
      observation that inactivating mutations of the WNK4 kinase domain did not
      completely abolish in vitro phosphorylation of OSR1/SPAK. Led by this, we
      identified a novel 40-kDa kinase that associates specifically with the COOH
      terminal half of WNK4 and is able to phosphorylate both WNK4 and SPAK/OSR1. We
      suggest that this 40-kDa kinase functions in the WNK4 signal transduction pathway
      and may mediate some of the physiological actions attributed to WNK4.

PMID- 19587143
TI  - Loss of size selectivity of the glomerular filtration barrier in rats following
      laparotomy and muscle trauma.
AB  - Posttraumatic microalbuminuria may be caused by either charge- or size-selective
      alterations in the glomerular filtration barrier, or both, and/or to a reduction
      in proximal tubular protein reabsorption. This study was performed to elucidate
      the pathophysiology of the increases in glomerular permeability occurring in rats
      exposed to a laparotomy or to a laparotomy and muscle trauma. In anesthetized
      Wistar rats (250-280 g), the left ureter was cannulated for urine collection,
      while simultaneously blood access was achieved. Rats were exposed to trauma by a
      laparotomy (L; n = 8), or by a combination of L and muscle trauma (MT; L+MT)
      induced by topical blunt injury of the abdominal muscles bilaterally. After L,
      muscles were crushed using hemostatic forceps at either 2 x 2 sites ("small" MT;
      n = 9), or at 2 x 5 sites ("large" MT; n = 9). Sham groups (n = 16), not exposed
      to a laparotomy, were used as controls. The glomerular sieving coefficients
      (theta) to polydisperse FITC-Ficoll-70/400 (molecular radius 13-80 A) were
      determined at 5 or 60 min after L and L+MT, respectively, from plasma and urine
      samples, and analyzed by high-performance size-exclusion chromatography. A tissue
      uptake technique was used to assess theta for (125)I-labeled serum albumin. L,
      with or without MT, increased theta for Ficoll(55-80A) and albumin rapidly and
      markedly. Theta-Ficoll(70A) thus increased approximately threefold, and theta for
      albumin significantly, for all trauma groups. According to the "two-pore model"
      of glomerular permeability, these changes mainly reflect an increase in the
      number of large pores in the glomerular filter without any primary changes in the
      charge-selective properties of the filter.

PMID- 19587144
TI  - GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.
AB  - Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative
      stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in
      response to injury. This can be a disadvantage as it may be associated with
      insufficient production of cytoprotective heme-degradation metabolites. We,
      therefore, explored whether 1) targeted HO-1 expression can be achieved in
      glomeruli without altering their physiological integrity and 2) this expression
      reduces proteinuria in immune injury induced by an anti-glomerular basement
      membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin
      promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and
      subsequently generated transgenic mice from the FVB/N parental strain. There was
      a 16-fold higher transgene expression in the kidney than nonspecific background
      (liver) while the transprotein immunolocalized in glomerular epithelial cells
      (GEC). There was no change in urinary protein excretion, indicating that GEC
      targeted HO-1 expression had no effect on glomerular protein permeability.
      Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and
      6) was significantly lower compared with wild-type controls. There was no
      significant change in renal expression levels of profibrotic (TGF-beta1) or anti
      inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These
      observations indicate that GEC-targeted HO-1 expression does not alter glomerular
      physiological integrity and reduces proteinuria in glomerular immune injury.

PMID- 19587145
TI  - Alterations of growth plate and abnormal insulin-like growth factor I metabolism
      in growth-retarded hypokalemic rats: effect of growth hormone treatment.
AB  - Hypokalemic tubular disorders may lead to growth retardation which is resistant
      to growth hormone (GH) treatment. The mechanism of these alterations is unknown.
      Weaning female rats were grouped (n = 10) in control, potassium-depleted (KD), KD
      treated with intraperitoneal GH at 3.3 mg x kg(-1) x day(-1) during the last week
      (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth
      retarded compared with CPF rats, the osseous front advance (+/-SD) being 67.07 +/
      10.44 and 81.56 +/- 12.70 microm/day, respectively. GH treatment did not
      accelerate growth rate. The tibial growth plate of KD rats had marked
      morphological alterations: lower heights of growth cartilage (228.26 +/- 23.58
      microm), hypertrophic zone (123.68 +/- 13.49 microm), and terminal chondrocytes
      (20.8 +/- 2.39 microm) than normokalemic CPF (264.21 +/- 21.77, 153.18 +/- 15.80,
      and 24.21 +/- 5.86 microm). GH administration normalized these changes except for
      the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I
      (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed
      downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes
      in their distribution as analyzed by immunohistochemistry and in situ
      hybridization. GH did not further modify IGF-I mRNA expression. KD rats had
      normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver
      IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses
      the structural and molecular alterations induced by potassium depletion on the
      growth plate and shows that the lack of response to GH administration is
      associated with persistence of the disturbed process of chondrocyte hypertrophy
      and depressed mRNA expression of local IGF-I in the growth plate.

PMID- 19587142
TI  - Cell biology and physiology of the uroepithelium.
AB  - The uroepithelium sits at the interface between the urinary space and underlying
      tissues, where it forms a high-resistance barrier to ion, solute, and water flux,
      as well as pathogens. However, the uroepithelium is not simply a passive barrier;
      it can modulate the composition of the urine, and it functions as an integral
      part of a sensory web in which it receives, amplifies, and transmits information
      about its external milieu to the underlying nervous and muscular systems. This
      review examines our understanding of uroepithelial regeneration and how
      specializations of the outermost umbrella cell layer, including tight junctions,
      surface uroplakins, and dynamic apical membrane exocytosis/endocytosis,
      contribute to barrier function and how they are co-opted by uropathogenic
      bacteria to infect the uroepithelium. Furthermore, we discuss the presence and
      possible functions of aquaporins, urea transporters, and multiple ion channels in
      the uroepithelium. Finally, we describe potential mechanisms by which the
      uroepithelium can transmit information about the urinary space to the other
      tissues in the bladder proper.

PMID- 19587146
TI  - Solute partitioning and filtration by extracellular matrices.
AB  - The physiology of glomerular filtration remains mechanistically obscure despite
      its importance in disease. The correspondence between proteinuria and foot
      process effacement suggests podocytes as the locus of the filtration barrier. If
      so, retained macromolecules ought to accumulate at the filtration barrier, an
      effect called concentration polarization. Literature data indicate macromolecule
      concentrations decrease from subendothelial to subepithelial glomerular basement
      membrane (GBM), as would be expected if the GBM were itself the filter. The
      objective of this study was to obtain insights into the possible role of the GBM
      in protein retention by performing fundamental experimental and theoretical
      studies on the properties of three model gels. Solute partitioning and filtration
      through thin gels of a commercially available laminin-rich extracellular matrix,
      Matrigel, were measured using a polydisperse polysaccharide tracer molecule,
      Ficoll 70. Solute partitioning into laminin gels and lens basement membrane (LBM)
      were measured using Ficoll 70. A novel model of a laminin gel was numerically
      simulated, as well as a mixed structure-random-fiber model for LBM. Experimental
      partitioning was predicted by numerical simulations. Sieving coefficients through
      thin gels of Matrigel were size dependent and strongly flux dependent. The
      observed flux dependence arose from compression of the gel in response to the
      applied pressure. Gel compression may alter solute partitioning into
      extracellular matrix at physiologic pressures present in the glomerular
      capillary. This suggests a physical mechanism coupling podocyte structure to
      permeability characteristics of the GBM.

PMID- 19587147
TI  - Mouse GLUT9: evidences for a urate uniporter.
AB  - GLUT9 (SLC2A9) is a newly described urate transporter whose function,
      characteristics, and localization have just started to be elucidated. Some
      transport properties of human GLUT9 have been studied in the Xenopus laevis
      oocyte expression system, but the type of transport (uniport, coupled transport
      system, stoichiometry ... .) is still largely unknown. We used the same
      experimental system to characterize in more detail the transport properties of
      mouse GLUT9, its sensitivity to several uricosuric drugs, and the specificities
      of two splice variants, mGLUT9a and mGLUT9b. [(14)C]urate uptake measurements
      show that both splice variants are high-capacity urate transporters and have a
      K(m) of approximately 650 microM. The well-known uricosuric agents benzbromarone
      (500 microM) and losartan (1 mM) inhibit GLUT9-mediated urate uptake by 90 and
      50%, respectively. Surprisingly, phloretin, a glucose-transporter blocker,
      inhibits [(14)C]urate uptake by approximately 50% at 1 mM. Electrophysiological
      measurements suggest that urate transport by mouse GLUT9 is electrogenic and
      voltage dependent, but independent of the Na(+) and Cl(-) transmembrane
      gradients. Taken together, our results suggest that GLUT9 works as a urate
      (anion) uniporter. Finally, we show by RT-PCR performed on RNA from mouse kidney
      microdissected tubules that GLUT9a is expressed at low levels in proximal
      tubules, while GLUT9b is specifically expressed in distal convoluted and
      connecting tubules. Expression of mouse GLUT9 in the kidney differs from that of
      human GLUT9, which could account for species differences in urate handling.

PMID- 19587148
TI  - Downregulation of claudin-2 expression in renal epithelial cells by metabolic
      acidosis.
AB  - Chronic metabolic acidosis (CMA) is associated with an inhibition of fluid
      reabsorption in the renal proximal tubule. The effects of CMA on paracellular
      transport across the renal epithelial tight junction (TJ) is unknown. Claudin-2
      is a transmembrane TJ-associated protein which confers TJ paracellular
      permeability to Na(+). We examined the effects of CMA on the expression of TJ
      transport proteins using both in vivo and in vitro models of CMA. The results
      showed downregulation of claudin-2 mRNA and protein expression in the cortex of
      rats subjected to the NH(4)Cl loading model of CMA. Madin-Darby canine kidney
      (MDCK) and HK-2 cells are models of renal epithelial cells and express claudin-2
      protein in their TJ. We examined the effects of acidic pH exposure on the
      expression of claudin-2 in MDCK and HK-2 renal epithelial cells. Exposure of MDCK
      cells to pH 6.96 medium caused a significant and reversible decrease in claudin-2
      protein abundance. A dose-response analysis of acidic medium exposure of MDCK and
      HK-2 cells demonstrated a downregulation of claudin-2 protein. The downregulation
      effect of acidic pH is specific to claudin-2 expression as the expression of
      other TJ-associated proteins (i.e., claudin-1, -3, -4, and -7, occludin, and
      zonula occludens-1) remained unchanged compared with control pH (7.40).
      Collectively, these data demonstrate that CMA downregulates the expression of
      claudin-2 likely through a direct effect of acidic pH. Potential physiological
      significance of these changes is discussed.

PMID- 19587149
TI  - Evaluation of the specificity of pneumococcal polysaccharide enzyme-linked
      immunosorbent assay and the effect of serum adsorption based on standard
      pneumococcal serogroup- or serotype-specific rabbit antisera.
AB  - Worldwide, Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity
      and mortality, especially in infants and elderly people. Pneumococcal capsular
      polysaccharides are well characterized, and more than 90 different serotypes have
      been identified. Serotype-specific antibodies against the capsular polysaccharide
      are produced during infection. Detection of antibodies against pneumococci by
      enzyme-linked immunosorbent assay (ELISA) is performed according to WHO
      guidelines, using antigens provided by ATCC. However, testing the ELISA for
      specificity is challenging due to the difficulty in obtaining human naive serum
      with pneumococcal antibodies as well as human serum with antibodies against a
      single serotype. The application of well-defined serotype-specific sera produced
      in animals to evaluate the specificity of the ATCC antigens and the effect of
      adsorption with cell wall and 22F polysaccharides has not been performed before,
      to our knowledge. In this study, the specificity of ATCC antigens (serotypes 4,
      6B, 9V, 14, 18C, 19F, and 23F) was tested by using commercial serotype-,
      serogroup-, and pool-specific pneumococcal rabbit antisera.

PMID- 19587150
TI  - Assessment of Mycobacterium tuberculosis OmpATb as a novel antigen for the
      diagnosis of bovine tuberculosis.
AB  - In the search for better tools to control bovine tuberculosis, the development of
      diagnostic tests with improved specificity and sensitivity has a high priority.
      We chose to search for novel immunodiagnostic reagents. In this study, Rv0899
      (outer membrane protein A of Mycobacterium tuberculosis [OmpATb]) was evaluated
      as a stimulation antigen in a gamma interferon (IFN-gamma) release assay to
      diagnose bovine tuberculosis. OmpATb induced IFN-gamma responses in cattle
      experimentally infected with M. bovis as early and as persistently as ESAT-6 and
      CFP-10, the current lead diagnostic antigens. In naturally infected cattle,
      OmpATb stimulated IFN-gamma production in 22 of 26 animals (85%). Importantly,
      OmpATb detected a portion of M. bovis-infected cattle which did not respond to
      ESAT-6 and CFP-10 (five of six cattle). The combined diagnostic sensitivity of
      OmpATb, ESAT-6, and CFP-10 for a preselected group consisting of naturally
      infected cattle with an overrepresentation of ESAT-6/CFP-10 nonresponders was 96%
      (25 of 26 animals). The specificity of OmpATb for uninfected cattle was 100% (27
      cattle were tested; 12 of them gave false-positive results with tuberculins). In
      summary, our results indicate that OmpATb has the potential to enhance the
      sensitivity of previously described diagnostic tests based on ESAT-6 and CFP-10
      and that the combined use of OmpATb, ESAT-6, CFP-10, and other proteins may
      achieve at least equal sensitivity to that obtained with purified protein
      derivative, but at a higher specificity. Further studies evaluating the
      diagnostic performance of OmpATb in combination with other proteins are ongoing.

PMID- 19587151
TI  - Bicentric evaluation of six anti-toxoplasma immunoglobulin G (IgG) automated
      immunoassays and comparison to the Toxo II IgG Western blot.
AB  - A comparative study of the Toxoplasma IgG(I) and IgG(II) Access (Access I and II,
      respectively; Beckman Coulter Inc.), AxSYM Toxo IgG (AxSYM; Abbott Diagnostics),
      Vidas Toxo IgG (Vidas; bioMerieux, Marcy l'Etoile, France), Immulite Toxo IgG
      (Immulite; Siemens Healthcare Diagnostics Inc.), and Modular Toxo IgG (Modular;
      Roche Diagnostics, Basel, Switzerland) tests was done with 406 consecutive serum
      samples. The Toxo II IgG Western blot (LDBio, Lyon, France) was used as a
      reference technique in the case of intertechnique discordance. Of the 406 serum
      samples tested, the results for 35 were discordant by the different techniques.
      Using the 175 serum samples with positive results, we evaluated the
      standardization of the titrations obtained (in IU/ml); the medians (second
      quartiles) obtained were 9.1 IU/ml for the AxSYM test, 21 IU/ml for the Access I
      test, 25.7 IU/ml for the Access II test, 32 IU/ml for the Vidas test, 34.6 IU/ml
      for the Immulite test, and 248 IU/ml for the Modular test. For all the
      immunoassays tested, the following relative sensitivity and specificity values
      were found: 89.7 to 100% for the Access II test, 89.7 to 99.6% for the Immulite
      test, 90.2 to 99.6% for the AxSYM test, 91.4 to 99.6% for the Vidas test, 94.8 to
      99.6% for the Access I test, and 98.3 to 98.7% for the Modular test. Among the
      406 serum samples, we did not find any false-positive values by two different
      tests for the same serum sample. Except for the Modular test, which prioritized
      sensitivity, it appears that the positive cutoff values suggested by the
      pharmaceutical companies are very high (either for economical or for safety
      reasons). This led to imperfect sensitivity, a large number of unnecessary
      serological follow-ups of pregnant women, and difficulty in determining the
      serological status of immunosuppressed individuals.

PMID- 19587153
TI  - Dietary carbohydrates and dental-systemic diseases.
AB  - Two contradictory hypotheses on the role of dietary carbohydrates in health and
      disease shape how dental-systemic associations are regarded. On one side, Cleave
      and Yudkin postulated that excessive dietary fermentable carbohydrate intake led
      in the absence of dental interventions such as fluorides-first to dental diseases
      and then to systemic diseases. Under this hypothesis, dental and systemic
      diseases shared-as a common cause-a diet of excess fermentable carbohydrates.
      Dental diseases were regarded as an alarm bell for future systemic diseases, and
      restricting carbohydrate intake prevented both dental and systemic diseases. On
      the opposite side, Keys postulated the lipid hypothesis: that excessive dietary
      lipid intake caused systemic diseases. Keys advocated a diet high in fermentable
      carbohydrate for the benefit of general health, and dental diseases became
      regarded as local dietary side effects. Because general health takes precedence
      over dental health when it comes to dietary recommendations, dental diseases
      became viewed as local infections; interventions such as fluorides, sealants,
      oral hygiene, antimicrobials, and dental fillings became synonymous with
      maintaining dental health, and carbohydrates were no longer considered as a
      common cause for dental-systemic diseases. These opposing dietary hypotheses have
      increasingly been put to the test in clinical trials. The emerging trial results
      favor Cleave-Yudkin's hypothesis and may affect preventive approaches for dental
      and systemic diseases.

PMID- 19587154
TI  - Metabolic syndrome and periodontitis: is oxidative stress a common link?
AB  - A review of pathological mechanisms that can explain the relationship between
      periodontitis and cardiovascular disease (CVD) is necessary to improve the
      management of both conditions. Metabolic syndrome is a combination of obesity,
      hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia, and
      dyslipidemia. All these have been examined in recent years in terms of their
      relationship to periodontitis. Reviewed data indicate an association between some
      of them (body mass index, high-density lipoprotein-cholesterol [HDL-C],
      triglycerides, high blood pressure, among others) and periodontitis. Oxidative
      stress may act as a potential common link to explain relationships between each
      component of metabolic syndrome and periodontitis. Both conditions show increased
      serum levels of products derived from oxidative damage, with a pro-inflammatory
      state likely influencing each other bidirectionally. Adipocytokines might
      modulate the oxidant/anti-oxidant balance in this relationship.

PMID- 19587152
TI  - Putative novel surface-exposed Streptococcus agalactiae protein frequently
      expressed by the group B streptococcus from Zimbabwe.
AB  - Group B streptococci (GBS) express a variety of surface-exposed and strain
      variable proteins which function as phenotypic markers and as antigens which are
      able to induce protective immunity in experimental settings. Among these
      proteins, the chimeric and immunologically cross-reacting alpha-like proteins are
      particularly important. Another protein, R3, which has been less well studied,
      occurred at a frequency of 21.5% in GBS from Zimbabwe and, notably, occurred in
      serotype V strains at a frequency of 75.9%. Working with rabbit antiserum raised
      against the R3 reference strain ATCC 49447 (strain 10/84; serotype V/R3) to
      detect the expression of the R3 protein, we recorded findings which suggested
      that strain 10/84 expressed a strain-variable protein antigen, in addition to R3.
      The antigen was detected by various enzyme-linked immunosorbent assay-based tests
      by using acid extract antigens or GBS whole-cell coats and by whole-cell-based
      Western blotting. We named the putative novel antigen the Z antigen. The Z
      antigen was a high-molecular-mass antigen that was susceptible to degradation by
      pepsin and trypsin but that was resistant to m-periodate oxidation and failed to
      show immunological cross-reactivity with any of a variety of other GBS protein
      antigens. The Z antigen was expressed by 33/121 (27.2%) of strains of a
      Zimbabwean GBS strain collection and by 64.2% and 72.4% of the type Ib and type V
      strains, respectively, and was occasionally expressed by GBS of other capsular
      serotypes. Thus, the putative novel GBS protein named Z showed distinct capsular
      antigen associations and presented as an important phenotypic marker in GBS from
      Zimbabwe. It may be an important antigen in GBS from larger areas of southern
      Africa. Its prevalence in GBS from Western countries is not known.

PMID- 19587155
TI  - Is obesity an oral bacterial disease?
AB  - The world-wide explosion of overweight people has been called an epidemic. The
      inflammatory nature of obesity is widely recognized. Could it really be an
      epidemic involving an infectious agent? In this climate of concern over the
      increasing prevalence of overweight conditions in our society, we focus on the
      possible role of oral bacteria as a potential direct contributor to obesity. To
      investigate this possibility, we measured salivary bacterial populations of
      overweight women. Saliva was collected from 313 women with a body mass index
      between 27 and 32, and bacterial populations were measured by DNA probe analysis.
      Levels in this group were compared with data from a population of 232 healthy
      individuals from periodontal disease studies. The median percentage difference of
      7 of the 40 bacterial species measured was greater than 2% in the saliva of
      overweight women. Classification tree analysis of salivary microbiological
      composition revealed that 98.4% of the overweight women could be identified by
      the presence of a single bacterial species (Selenomonas noxia) at levels greater
      than 1.05% of the total salivary bacteria. Analysis of these data suggests that
      the composition of salivary bacteria changes in overweight women. It seems likely
      that these bacterial species could serve as biological indicators of a developing
      overweight condition. Of even greater interest, and the subject of future
      research, is the possibility that oral bacteria may participate in the pathology
      that leads to obesity.

PMID- 19587156
TI  - Smoking cessation alters subgingival microbial recolonization.
AB  - Smoking cessation improves the clinical manifestations of periodontitis; however,
      its effect on the subgingival biofilm, the primary etiological agent of
      periodontitis, is unclear. The purpose of this study was to investigate,
      longitudinally, if smoking cessation altered the composition of the subgingival
      microbial community, by means of a quantitative, cultivation-independent assay
      for bacterial profiling. Subgingival plaque was collected at baseline, and 3, 6,
      and 12 months post-treatment from smokers who received root planing and smoking
      cessation counseling. The plaque was analyzed by terminal restriction fragment
      length polymorphism (t-RFLP). Microbial profiles differed significantly between
      smokers and quitters at 6 and 12 months following smoking cessation. The
      microbial community in smokers was similar to baseline, while quitters
      demonstrated significantly divergent profiles. Changes in bacterial levels
      contributed to this shift. These findings reveal a critical role for smoking
      cessation in altering the subgingival biofilm and suggest a mechanism for
      improved periodontal health associated with smoking cessation.

PMID- 19587157
TI  - Structural integrity of enamel: experimental and modeling.
AB  - Tooth enamel is the hardest tissue in the human body and is directly responsible
      for dental function. Due to its non-regenerative nature, enamel is unable to heal
      and repair itself biologically after damage. We hypothesized that with its unique
      microstructure, enamel possesses excellent resistance to contact-induced damage,
      regardless of loading direction. By combining instrumented indentation tests with
      microstructural analysis, we report that enamel can absorb indentation energy
      through shear deformation within its protein layers between apatite crystallites.
      Moreover, a near-isotropic inelastic response was observed when we analyzed
      indentation data in directions either perpendicular or parallel to the path of
      enamel prisms. An "effective" crystal orientation angle, 33 degrees -34 degrees ,
      was derived for enamel microstructure, independent of the loading direction.
      These findings will help guide the design of the nanostructural architecture of
      dental restorative materials.

PMID- 19587158
TI  - Novel Golgi protein, GoPro49, is a specific dental follicle marker.
AB  - GoPro49 is a recently identified, novel Golgi protein that is expressed in
      embryonic mesenchymal tissues, including dental follicle. In the present study,
      we have tested the hypothesis that the gene is a specific marker for the dental
      follicle, and examined its expression during the development of mouse incisors
      and molars. In situ hybridization showed that GoPro49 is expressed in dental
      follicles from bud to post-eruption stages. The expression is intense throughout
      the dental follicle during crown development, and persists in the root follicle
      during root development. In the forming periodontal ligament, GoPro49 expression
      is down-regulated upon differentiation of the follicle cells to cementoblasts and
      osteoblasts marked by Bsp1. In cultured dental follicle cells, the GoPro49
      protein co-localizes with beta-COP, suggesting that GoPro49 may function in the
      secretory pathway. We conclude that GoPro49 is a novel, specific marker for the
      dental follicle and can be used to identify this tissue. ABBREVIATIONS: Bsp1,
      bone sialoprotein 1; GoPro49, Golgi protein 49 kDa; E16, embryonic day 16; HERS,
      Hertwig's epithelial root sheath; PDL, periodontal ligament; dpn, day post-natal.

PMID- 19587159
TI  - Function of beta1 integrin in oral epithelia and tooth bud morphogenesis.
AB  - Integrin beta1 is critical for basement membrane organization and hair follicle
      morphogenesis in the skin epidermis; however, less is known about its function in
      the developing oral epithelium. Since the skin and oral epithelia share
      structural similarity, we hypothesized that beta1 integrin function would be
      critical for the normal development of oral epithelium and tooth buds. The
      conditional (oral mucosa-specific) beta1 integrin knockout (KO) mice displayed
      severe disruption of the basement membrane of the tongue epithelium and
      developing tooth buds. Interestingly, unlike the developing hair follicles, early
      morphological development of the KO molar tooth buds was normal. However,
      subsequent morphogenetic events, such as cusp formation, cervical loop down
      growth, and ameloblast polarization, did not occur normally. Primary KO oral
      keratinocytes showed defective cell spreading and robust focal adhesions. Our
      studies indicate that beta1 integrin plays an essential role in the normal
      development of the oral epithelium and its appendages.

PMID- 19587160
TI  - Roles of the primary cilium component Polaris in synchondrosis development.
AB  - Primary cilia regulate several developmental processes and mediate hedgehog
      signaling. To study their roles in cranial base development, we created
      conditional mouse mutants deficient in Polaris, a critical primary cilium
      component, in cartilage. Mutant post-natal cranial bases were deformed, and their
      synchondrosis growth plates were disorganized. Expression of Indian hedgehog,
      Patched-1, collagen X, and MMP-13 was reduced and accompanied by decreases in
      endochondral bone. Interestingly, there was excessive intramembranous
      ossification along the perichondrium, accompanied by excessive Patched-1
      expression, suggesting that Ihh distribution was wider and responsible for such
      excessive response. Indeed, expression of heparan sulfate proteoglycans (HS-PGs),
      normally involved in restricting hedgehog distribution, was barely detectable in
      mutant synchondroses. Analyses of the data provides further evidence for the
      essential roles of primary cilia and hedgehog signaling in cranial base
      development and chondrocyte maturation, and point to a close interdependence
      between cilia and HS-PGs to delimit targets of hedgehog action in synchondroses.

PMID- 19587161
TI  - PTHrP induces Notch signaling in periodontal ligament cells.
AB  - Periodontal ligament (PDL) cells are known to play important roles in tooth
      eruption and alveolar bone metabolism. We previously reported that PTHrP
      increases RANKL expression in human PDL cells, suggesting that it promotes
      odontoclastic root resorption during tooth eruption. While it is known that Notch
      related genes play a key role during bone development, the role of the Notch
      signaling pathway in PDL cells during tooth and bone resorption is less clear. We
      hypothesized that PTHrP induces a Notch ligand in PDL cells and thereby regulates
      osteo- and odontoclastogenesis. We found that PTHrP increased Notch1 ligand
      Jagged1 expression in human PDL cells in a dose- and time-dependent manner. PTHrP
      induced Jagged1 up-regulation was mediated by PKA activation, but not by PKC.
      Jagged1 also promoted RANKL-induced osteoclastogenesis. These results demonstrate
      that PTHrP induces Jagged1 expression in PDL cells, leading to osteo- and
      odontoclastogenesis, and thus likely promoting tooth and alveolar bone
      resorption.

PMID- 19587163
TI  - Amphiregulin induces proliferative activities in osseous dysplasia.
AB  - Human osseous dysplasia (OD) is a benign fibro-osseous neoplasm of periodontal
      ligament origin in which normal bone is replaced with fibrous connective tissue
      containing abnormal bone or cementum. However, cellular differentiation and
      proliferation in OD have not been fully elucidated. In vitro culture systems have
      distinct advantages for analytical studies. Therefore, we established
      immortalized cell lines (OD-1) from OD lesions of the jaw from an individual with
      gnathodiaphyseal dysplasia (GDD). We hypothesized that OD-1 had a characteristic
      growth mechanism different from that of mineralized-associated cells such as
      osteoblasts. To clarify the difference of gene expression patterns between OD-1
      and osteoblasts, we compared the profiles of genes expressed in the 2 cell types
      by microarray analysis. We identified amphiregulin to be highly expressed in OD-1
      compared with osteoblasts and gingival fibroblasts. OD-1 showed proliferative
      activities regulated in an autocrine manner by amphiregulin, and amphiregulin may
      play a significant role in the proliferation of OD.

PMID- 19587162
TI  - IL-1beta inhibits TGFbeta in the temporomandibular joint.
AB  - Similarly to humans, healthy, wild-type mice develop osteoarthritis, including of
      the temporomandibular joint (TMJ), as a result of aging. Pro-inflammatory
      cytokines, such as IL-1beta, IL-6, and TNFalpha, are known to contribute to the
      development of osteoarthritis, whereas TGFbeta has been associated with articular
      regeneration. We hypothesized that a balance between IL-1beta and TGFbeta
      underlies the development of TMJ osteoarthritis, whereby IL-1beta signaling down
      regulates TGFbeta expression as part of disease pathology. Our studies in wild
      type mice, as well as the Col1-IL1beta(XAT) mouse model of osteoarthritis,
      demonstrated an inverse correlation between IL-1beta and TGFbeta expression in
      the TMJ. IL-1beta etiologically correlated with joint pathology, whereas TGFbeta
      expression associated with IL-1beta down-regulation and improvement of articular
      pathology. Better understanding of the underlying inflammatory processes during
      disease will potentially enable us to harness inflammation for orofacial tissue
      regeneration.

PMID- 19587164
TI  - Sclerostin in mineralized matrices and van Buchem disease.
AB  - Sclerostin is an inhibitor of bone formation expressed by osteocytes. We
      hypothesized that sclerostin is expressed by cells of the same origin and also
      embedded within mineralized matrices. In this study, we analyzed (a) sclerostin
      expression using immunohistochemistry, (b) whether the genomic defect in
      individuals with van Buchem disease (VBD) was associated with the absence of
      sclerostin expression, and (c) whether this was associated with hypercementosis.
      Sclerostin was expressed by cementocytes in mouse and human teeth and by
      mineralized hypertrophic chondrocytes in the human growth plate. In individuals
      with VBD, sclerostin expression was absent or strongly decreased in osteocytes
      and cementocytes. This was associated with increased bone formation, but no overt
      changes in cementum thickness. In conclusion, sclerostin is expressed by all 3
      terminally differentiated cell types embedded within mineralized matrices:
      osteocytes, cementocytes, and hypertrophic chondrocytes.

PMID- 19587167
TI  - Proceedings of the 37th and 38th Annual Meetings of the Society for Computers in
      Psychology (SCiP).

PMID- 19587165
TI  - Localization of P. gingivalis in preterm delivery placenta.
AB  - Increasing evidence suggests an association between periodontal disease and
      adverse pregnancy outcomes. Although infection is considered as a risk factor for
      preterm delivery, the localization of oral bacteria or their antigens in
      chorioamnionitis placental tissue has never been demonstrated. This study was
      devised to test the hypothesis that periodontal pathogens may be present and
      affect human placenta in cases of chorioamnionitis. Using immunocytochemistry, we
      have identified the presence of Porphyromonas gingivalis antigens in placental
      tissues. The antigens were detected in the placental syncytiotrophoblasts,
      chorionic trophoblasts, decidual cells, and amniotic epithelial cells, as well as
      the vascular cells. There was a substantial increase in immunostaining intensity
      of the tissues sectioned from women with chorioamnionitis compared to those
      experiencing normalterm pregnancy, p < 0.019 (Mann-Whitney test). These results
      suggest that P. gingivalis may commonly colonize placental tissue, and that the
      presence of the organism may contribute to preterm delivery.

PMID- 19587169
TI  - Millisecond precision psychological research in a world of commodity computers:
      new hardware, new problems?
AB  - Since the publication of Plant, Hammond, and Turner (2004), which highlighted a
      pressing need for researchers to pay more attention to sources of error in
      computer-based experiments, the landscape has undoubtedly changed, but not
      necessarily for the better. Readily available hardware has improved in terms of
      raw speed; multi core processors abound; graphics cards now have hundreds of
      megabytes of RAM; main memory is measured in gigabytes; drive space is measured
      in terabytes; ever larger thin film transistor displays capable of single-digit
      response times, together with newer Digital Light Processing multimedia
      projectors, enable much greater graphic complexity; and new 64-bit operating
      systems, such as Microsoft Vista, are now commonplace. However, have millisecond
      accurate presentation and response timing improved, and will they ever be
      available in commodity computers and peripherals? In the present article, we used
      a Black Box ToolKit to measure the variability in timing characteristics of
      hardware used commonly in psychological research.

PMID- 19587168
TI  - A transcranial Doppler sonography study of shoot/don't-shoot responding.
AB  - The purpose of this study was to examine the relationship between changes in
      cerebral blood-flow velocity and performance on a speeded shoot/don't-shoot task.
      Brain activity as indicated by cerebral blood-flow velocity (hemovelocity) was
      recorded using the transcranial Doppler ultrasonography. A shoot/don't-shoot
      decision-making task presented participants with threat/nonthreat stimuli in the
      form of bull's-eye images of various colors. Participants were required to shoot
      threat targets using a laser-modified handgun. Results support a vigilance
      decrement in both the performance measures and hemovelocity. Performance, as
      measured by reaction time, number of hits, and marksmanship, decreased across the
      length of the vigil. Hemovelocity slowed across the left and right hemispheres as
      the task progressed, and hemovelocity was slower in the right hemisphere than in
      the left hemisphere.

PMID- 19587170
TI  - A hybrid approach to experimental control.
AB  - In the present article, I describe a new, hybrid approach to experimental control
      that combines the best features of general-purpose programs and specific
      experiment programs. First, experimental control objects are developed in an
      object-oriented programming environment. Then, an XML file is used to select and
      arrange those control objects in order to carry out an experiment. A wide range
      of experiments can be implemented by specifying the arrangement of the control
      objects in the XML file, while, at the same time, the set of control objects can
      be easily extended for more demanding applications. An overview of a system using
      this approach is provided, along with some examples.

PMID- 19587171
TI  - Social psychophysics: using psychophysics to answer "social" questions with
      PsychoPro.
AB  - Complex social stimuli (like faces) can be studied using a methodology typically
      reserved for studying lights, tones, and colors: psychophysics. Given that
      psychophysics examines how humans detect and respond to stimuli in their
      environment, we can extend that to the study of how humans detect social stimuli
      in the environment. Using psychophysical methodology to answer "social" questions
      provides another dimension of experimental manipulation and control to the
      diverse array of methodologies already used by social psychologists. In this
      article, we review psychophysical methodology, provide a rationale for social
      psychophysics, describe an easy-to-use software program called PsychoPro, for
      collecting psychophysical data, and present data collected using this program to
      examine racial thresholds that provide evidence for a cognitive gating mechanism
      for racial information that impacts face processing (MacLin & MacLin, 2007, in
      press; MacLin, MacLin, & Peterson, 2008).

PMID- 19587172
TI  - Real-time generation of representations for cognitive models.
AB  - Computerized models of human cognition and behavior have been used to help
      researchers refine their theories of cognitive processes. Two difficulties
      inherent in using these cognitive models are that building representations of to
      be-modeled groups or individuals is (1) time-consuming and (2) prone to error
      when performed manually. The use of computerized tools to build representations
      for cognitive models could alleviate these problems. Such a set of tools has been
      developed and applied to the task of modeling individual aviation pilots
      performing flight maneuvers in real time. A study conducted with 27 pilots
      confirms the accuracy of the computer-generated representations.

PMID- 19587173
TI  - How to support learning from multiple hypertext sources.
AB  - In the present study, we investigated three factors that were assumed to have a
      significant influence on the success of learning from multiple hypertexts, and on
      the construction of a documents model in particular. These factors were task
      (argumentative vs. narrative), available text material (with vs. without primary
      sources), and presentation format (active vs. static). The study was conducted
      with the help of the combination of three tools (DEWEX, Chemnitz LogAnalyzer, and
      SummTool) developed for Web-based experimenting. The results show that the task
      is the most important factor for successful learning from multiple hypertexts.
      Depending on the task, the participants were either able or unable to apply
      adequate strategies, such as considering the source information. It was also
      observed that argumentative tasks were supported by an active hypertext
      presentation format, whereas performance on narrative tasks increased with a
      passive presentation format. No effect was shown for the type of texts available.

PMID- 19587174
TI  - More data trumps smarter algorithms: comparing pointwise mutual information with
      latent semantic analysis.
AB  - Computational models of lexical semantics, such as latent semantic analysis, can
      automatically generate semantic similarity measures between words from
      statistical redundancies in text. These measures are useful for experimental
      stimulus selection and for evaluating a model's cognitive plausibility as a
      mechanism that people might use to organize meaning in memory. Although humans
      are exposed to enormous quantities of speech, practical constraints limit the
      amount of data that many current computational models can learn from. We follow
      up on previous work evaluating a simple metric of pointwise mutual information.
      Controlling for confounds in previous work, we demonstrate that this metric
      benefits from training on extremely large amounts of data and correlates more
      closely with human semantic similarity ratings than do publicly available
      implementations of several more complex models. We also present a simple tool for
      building simple and scalable models from large corpora quickly and efficiently.

PMID- 19587175
TI  - A mixed-effects expectancy-valence model for the Iowa gambling task.
AB  - The Iowa gambling task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994) was
      developed to simulate real-life decision making under uncertainty. The task has
      been widely used to examine possible neurocognitive deficits in normal and
      clinical populations. Busemeyer and Stout (2002) proposed the expectancy-valence
      (EV) model to explicitly account for individual participants' repeated choices in
      the IGT. Parameters of the EV model presumably measure different psychological
      processes that underlie performance on the task, and their values may be used to
      differentiate individuals across different populations. In the present article,
      the EV model is extended to include both fixed effects and subject-specific
      random effects. The mixed-effects EV model fits the nested structure of
      observations in the IGT naturally and provides a unified procedure for parameter
      estimation and comparisons among groups of populations. We illustrate the utility
      of the mixed-effects approach with an analysis of gender differences using a real
      data set. A simulation study was conducted to verify the advantages of this
      approach.

PMID- 19587176
TI  - Randomization tests and the unequal-N/unequal-variance problem.
AB  - When both the variance and the N are unequal in a two-group design, the
      probability of a Type I error shifts from the nominal 5% error rate. The
      probability is too liberal when the small cell has the larger variance and too
      conservative when the large cell has the larger variance. We present an algorithm
      to circumvent the problem when the smaller group has the larger variance and
      show, by simulation, that the algorithm brings the error rate back to the nominal
      value without sacrificing the ability to detect true effects.

PMID- 19587177
TI  - PsychoPro 2.0: using multidimensional scaling to examine the perceptual
      categorization of race.
AB  - Recently, researchers examining cognitive mechanisms involved in the detection of
      racial markers have been using psychophysics to examine perceptual thresholds
      delineating race using a program called PsychoPro (MacLin, MacLin, Peterson,
      Chowdhry, & Joshi, 2009). PsychoPro allows researchers to collect data using
      facial stimuli morphed along a racial continuum with psychophysical methodology.
      PsychoPro 2.0 was updated so researchers could collect paired-comparison data
      that can then be analyzed using multidimensional scaling (MDS). MDS allows
      researchers to examine the perceptions of racial boundaries along perceptual
      dimensions not bounded by the stimulus continuum, by having the observer make
      paired comparisons to racial stimuli based on their perceived similarity. Results
      indicate that ratings were made on the basis of at least six different racial
      dimensions that suggest the emergence of a third race not represented by the
      original morph starting images. Details of the software, the new paired
      comparison feature and its relevance in psychophysical studies in general and
      racial categorization in particular are presented.

PMID- 19587178
TI  - Using SMS text messaging for teaching and data collection in the behavioral
      sciences.
AB  - Recent interest in university teaching has focused on interactivity in lectures
      and practical classes, and teachers in several fields have set up systems in
      which students can interact with the lecturer using mobile-phone-based SMS text
      messaging. This approach has particular potential in psychology, where students
      could use SMS messaging as a way of responding in simple psychology experiments
      or demonstrations. We describe a simple architecture for an SMS-based responding,
      using an SMS-to-HTTP message relay service, and a PHP/MySQL input-output handler.
      We describe briefly two experiments we have run using the system. The first
      experiment examined anchoring effects in an SMS-based auction. The second
      experiment examined delay discounting, with participants indicating their
      intertemporal preferences using SMS. Finally, we evaluate the feedback we
      obtained from students about the practical and conceptual issues surrounding text
      message-based responding.

PMID- 19587179
TI  - The components of paraphrase evaluations.
AB  - Two sentences are paraphrases if their meanings are equivalent but their words
      and syntax are different. Paraphrasing can be used to aid comprehension,
      stimulate prior knowledge, and assist in writing-skills development. As such,
      paraphrasing is a feature of fields as diverse as discourse psychology,
      composition, and computer science. Although automated paraphrase assessment is
      both commonplace and useful, research has centered solely on artificial, edited
      paraphrases and has used only binary dimensions (i.e., is or is not a
      paraphrase). In this study, we use an extensive database (N=1,998) of natural
      paraphrases generated by high school students that have been assessed along 10
      dimensions (e.g., semantic completeness, lexical similarity, syntactical
      similarity). This study investigates the components of paraphrase quality
      emerging from these dimensions and examines whether computational approaches can
      simulate those human evaluations. The results suggest that semantic and syntactic
      evaluations are the primary components of paraphrase quality, and that
      computationally light systems such as latent semantic analysis (semantics) and
      minimal edit distances (syntax) present promising approaches to simulating human
      evaluations of paraphrases.

PMID- 19587180
TI  - The efficacy of a Web-based counterargument tutor.
AB  - In two experiments, we developed and tested an interactive Web-based tutor to
      help students identify and evaluate counterarguments. In Experiment 1, we
      determined the extent to which high- and low-argumentationability participants
      were able to identify counterarguments. We tested the effectiveness of having
      participants read didactic text regarding counterarguments and highlight claims.
      Both preparations had some positive effects that were often limited to high
      ability participants. The Web-based intervention included interactive exercises
      on identifying and using counterarguments. Web-based presentation was state
      driven, using a Java Server Pages page. As participants progressively identified
      argument elements, the page changed display state and presented feedback by
      checking what the user clicked against elements that we had coded in XML
      beforehand. Instructions and feedback strings were indexed by state, so that
      changing state selected new text to display. In Experiment 2, the tutor was
      effective in teaching participants to identify counterarguments, recognize
      responses, and determine whether counterarguments were rebutted, dismissed, or
      conceded.

PMID- 19587181
TI  - Web-based image norming: how do object familiarity and visual complexity ratings
      compare when collected in-lab versus online?
AB  - It has been demonstrated previously that, for some experimental paradigms, Web
      based research can reliably replicate lab-based results. Yet questions remain as
      to what types of research can be reproduced, and where differences arise when
      they cannot be. The present article examines the effect of research location
      (laboratory vs. online) on normative data collection tasks. Specifically,
      participants were randomly assigned to a laboratory or online condition and were
      asked to rate 593 photorealistic images on the basis of object familiarity
      (N=103) and object visual complexity (N=98). Dependent measures were compared
      across location conditions, including response latencies and image rating
      agreement. Our results suggest that norming data collected online are reliable,
      but an interesting interplay between task type and research location was
      observed. Specifically, we found that participating online (i.e., a more familiar
      environment) leads to systematically higher familiarity ratings than in the lab
      (i.e., an unfamiliar environment). These differences are not found when the
      alternate complexity rating task is used.

PMID- 19587182
TI  - Allocation of effort as a function of payoffs for individual tasks in a
      multitasking environment.
AB  - SYNWORK1 software allows the examination of how payoffs affect the allocation of
      effort by people when they perform four different tasks (memory search,
      arithmetic, visual monitoring, and auditory monitoring). In a previous study
      (Wang, Proctor, & Pick, 2007), we showed that participants adopted multitasking
      strategies allocating relative effort appropriate to payoff differences between
      the arithmetic and memory tasks, but that they exhibited residual effects of
      prior payoffs when the payoffs were switched. In the present study, we varied the
      payoff in two different experiments for only one of these tasks, the memory task
      in Experiment 1 and the arithmetic task in Experiment 2. Doing this allowed
      consideration of performance for both the task for which payoff changed
      explicitly and the other cognitive task, for which the payoff difference was
      implicit (i.e., relative to the explicit payoff that was manipulated). Although
      participants adjusted performance on the task for which the payoff explicitly
      varied, the payoff manipulation had less effect than did the explicit payoff
      manipulations for both tasks used previously. Also, the change in effort on a
      task resulting from explicitly increasing its payoff was less than that from
      decreasing the payoff. SYNWORK1 is a good environment for studying multitasking,
      but has several limitations that need to be addressed to provide a synthetic work
      environment that allows investigation of a wider range of theoretically relevant
      issues.

PMID- 19587183
TI  - Proceedings of the 6th International Conference on Methods and Techniques in
      Behavior Research, Maastricht, The Netherlands, August 26-29, 2008.

PMID- 19587184
TI  - Identifying and analyzing the construction and effectiveness of offensive plays
      in basketball by using systematic observation.
AB  - In the field of sports research, there is a growing need for the rigorous
      collection of data that provide empirical evidence about the complex reality they
      refer to. Although sports psychology research has advanced considerably in recent
      years, in both extent and quality, one area of research that remains relatively
      unexplored is the dynamics of the sports group and the influence of the group on
      its members (George & Feltz, 1995; Widmeyer, Brawley, & Carron, 1992). Key
      aspects in this regard include the presence of regularities that are not
      detectable through visual inference or traditional methods of data analysis, the
      lack of standard observation instruments, and, assuming priority, the need to
      develop powerful, computerized coding systems, all of which must form part of an
      approach that is suitable for natural and habitual contexts. The present study is
      part of a broader research project concerning ACB teams (first Spanish basketball
      division) and considers the interaction context before teams try to score (where
      this is understood as how teams create scoring opportunities) as the core aspect
      that links team play. This investigation proposes a new model of analysis for
      studying the effectiveness and construction of offensive basketball plays in
      order to identify their outcomes, thus providing coaches with an important device
      for improving or consolidating them.

PMID- 19587185
TI  - The Observer XT: a tool for the integration and synchronization of multimodal
      signals.
AB  - The Observer was originally developed as a manual event recorder for the
      collection, management, analysis, and presentation of observational data in
      animals. Because of the flexibility of later versions, it became clear that The
      Observer was suitable for almost any study involving collection of observational
      data in both animals and humans. Furthermore, the most recent version of The
      Observer (The Observer XT) allows the integration and synchronization of
      multimodal signals from various sources, such as observational, video, tracking,
      and physiological data. This article describes how The Observer XT was used to
      integrate and synchronize video, observational, tracking, and physiological data
      from an experiment carried out in 2001 at the Wageningen Institute of Animal
      Sciences of Wageningen University and Research Centre. The integration and
      synchronization of these multimodal signals in The Observer XT allows the user to
      draw a more complete picture of the phenomena under study.

PMID- 19587186
TI  - An improved screw-free method for electrode implantation and intracranial
      electroencephalographic recordings in mice.
AB  - We recently developed a glue-based method for the implantation of intracranial
      electrodes in mice. Our approach is to secure a preconstructed electrode array
      using a cyanoacrylate-based glue (similar to Krazy Glue). This method is
      applicable to both young and aging mice and is suitable for long-term
      electroencephalographic recordings. In the present experiment, we explored
      whether the glue-based method is capable of securing individual electrodes in
      addition to securing the electrode array. C57 black mice aged 25-35 days or 13-19
      months were operated on under isoflurane anesthesia. Monopolar or bipolar
      electrodes were inserted independently in the ipsilateral hippocampal CA3 and
      entorhinal cortical areas, and they were fixed onto the skull using the glue
      together with dental acrylic, but without anchoring screws. We found that the
      implanted electrodes were stable and allowed repeat intracranial recordings and
      electrical stimulation in freely moving mice.

PMID- 19587187
TI  - Measuring and making decisions for social reciprocity.
AB  - Social reciprocity may explain certain emerging psychological processes likely to
      be founded on dyadic relations. Although indexes and statistics have been
      proposed to measure and make statistical decisions regarding social reciprocity
      in groups, these tools were generally developed to identify association patterns
      rather than to quantify the discrepancies between what each individual addresses
      to his or her partners and what is received from those partners in return.
      Additionally, social researchers' interest extends beyond measuring groups at the
      global level because dyadic and individual measurements are also necessary for
      proper descriptions of social interactions. This study is concerned with a new
      statistic for measuring social reciprocity at the global level and with
      decomposing that statistic in order to identify which dyads and individuals
      account for a significant part of asymmetry in social interactions. In addition
      to a set of indexes, some exact analytical results are derived, and a way of
      making statistical decisions is proposed.

PMID- 19587188
TI  - A method for the control of eating rate: a potential intervention in eating
      disorders.
AB  - A method for the control of eating rate gave subjects feedback from a computer
      screen on how much and at what rate to eat during a meal. The method also allowed
      us to record the development of satiety during the meal. Linear eaters--that is,
      women selected for eating at an approximately constant rate--underate when
      challenged to eat at a lower rate and overate when challenged to eat at a higher
      rate, thereby modeling the eating behavior of patients with anorexia nervosa and
      binge eating disorder, respectively. In both cases, the women's postmeal
      perception of satiety mimicked that of the respective patient group. The results
      provide support for the notion that linear eaters have the capacity to exhibit
      disordered eating.

PMID- 19587189
TI  - Measuring biting behavior induced by acute stress in the rat.
AB  - Previous reports have indicated that biting behavior is enhanced in rats that are
      subject to acute stress. Several methods have been proposed for studying this
      phenomenon, one of which is the electromyography (EMG) of the jaw muscles. In
      this study, we compared total EMG activity with the EMG activity related to
      biting behavior, as determined by video monitoring, before and after restraint
      stress. Wistar albino rats (150 g) were subject to surgery for electrode
      placement 48 h before measurements. The EMG activity of the masseter muscle on
      one side was recorded for 10 min before and immediately after 30 min of restraint
      stress. Restraint stress increased jaw muscle EMG activity, although some of the
      activity was related to behaviors other than biting. Recording the EMG activity
      of jaw muscles is useful for measuring the stress response in rats, but careful
      video monitoring is needed if biting behavior is to be studied in particular.

PMID- 19587190
TI  - Streams and patterns in behavior as challenges for future technologies.
AB  - How we divide and recombine processes that underlie integrated patterns of
      behavior represents one of the most fundamental problems in all behavioral
      science. Avenues of insight range from naturalistic observations to the most
      advanced technological advances in the recording and analysis of behavioral
      sequences. Members of the symposium on "Streams and Patterns in Behavior,"
      Maastricht Conference on Measuring Behavior, offered important complementary
      approaches to issues that are common in all analyses of behavioral patterns,
      across time scales and levels of organization. Rodent grooming was emphasized as
      one model system, but contributors also offered insights on a range of issues
      relevant to our deeper understanding of exploration, emotions, consciousness, and
      human neurological disorders.

PMID- 19587191
TI  - Multivariate data handling in the study of rat behavior: an integrated approach.
AB  - The aim of the present article is to provide a methodological description of
      various approaches to multivariate data handling in the study of rodent behavior.
      To this purpose, 42 male Wistar rats were tested in an open field, and their
      behavior was recorded through a digital video camera for a subsequent analysis by
      means of a software coder. After a preliminary evaluation of descriptive features
      such as durations and percent distributions, we carried out different kinds of
      multivariate approaches represented by stochastic, cluster, adjusted residual,
      and T-pattern analyses. In the attempt to depict behavior in a straightforward
      way, the results of each analysis were graphically illustrated through path
      diagrams, dendrograms, histograms, and tree-shaped T-patterns. Path diagrams
      showed a clear behavioral convergence toward immobile sniffing; dendrograms
      highlighted three different dyadic clusters: walking/climbing, immobile
      sniffing/immobility, and paw-licking/grooming; adjusted residuals confirmed, for
      the same patterns, highly significant association values; finally, T-pattern
      analysis showed a highly recurring temporal sequence of events encompassing
      walking, climbing, immobile sniffing, and immobility. Such results, drawing
      attention to specific behavioral patternings, strengthen and extend previous
      findings on rodent behavior. We suggest that T-pattern analysis, integrated with
      other multivariate approaches, can provide a more detailed and complete rat
      behavior representation, very different from classical quantitative approaches.

PMID- 19587192
TI  - Observation system for the control of the hive environment by the honeybee (Apis
      mellifera).
AB  - The honeybee can control its hive environment to survive drastic changes in the
      field environment. To study the control of multiple environmental factors by
      honeybees, in this experiment, we developed a continual and simultaneous
      monitoring system for the temperature, moisture, and carbon dioxide (CO2)
      concentration in a honeybee hive. Changes in hive weight, CO2 production rate,
      and honeybee behavior were also monitored to estimate energy costs and behavioral
      activity for the environmental regulation. Measurements were conducted in August
      2008. We found that the honeybee hive has a microclimate different from the
      ambient climate, and that the difference was partly accompanied by changes in
      honeybee activity. Our results also suggest that hive temperature, humidity, and
      CO2 concentrations are controlled by different mechanisms. Additional monitoring
      of the hive environment and honeybee behavior for longer periods would enable us
      to understand the mechanisms of environmental control by honeybees, which is one
      of the behaviors that define honeybees as social insects.

PMID- 19587194
TI  - Acoustic sleepiness detection: framework and validation of a speech-adapted
      pattern recognition approach.
AB  - This article describes a general framework for detecting sleepiness states on the
      basis of prosody, articulation, and speech-quality-related speech
      characteristics. The advantages of this automatic real-time approach are that
      obtaining speech data is nonobstrusive and is free from sensor application and
      calibration efforts. Different types of acoustic features derived from speech,
      speaker, and emotion recognition were employed (frame-level-based speech
      features). Combing these features with high-level contour descriptors, which
      capture the temporal information of frame-level descriptor contours, results in
      45,088 features per speech sample. In general, the measurement process follows
      the speech-adapted steps of pattern recognition: (1) recording speech, (2)
      preprocessing, (3) feature computation (using perceptual and signal-processing
      related features such as, e.g., fundamental frequency, intensity, pause patterns,
      formants, and cepstral coefficients), (4) dimensionality reduction, (5)
      classification, and (6) evaluation. After a correlation-filter-based feature
      subset selection employed on the feature space in order to find most relevant
      features, different classification models were trained. The best model-namely,
      the support-vector machine-achieved 86.1% classification accuracy in predicting
      sleepiness in a sleep deprivation study (two-class problem, N=12; 01.00-08.00
      a.m.).

PMID- 19587193
TI  - Automatic analysis of altered gait in arylsulphatase A-deficient mice in the open
      field.
AB  - In current research with laboratory animals, observing their dynamic behavior or
      locomotion is a labor-intensive task. Automatic continuous monitoring can provide
      quantitative data on each animal's condition and coordination ability. The
      objective of the present work is to develop an automated mouse observation system
      integrated with a conventional open-field test for motor function evaluation.
      Data were acquired from 86 mice having a targeted disruption of the
      arylsulphatase A (ASA) gene and having lowered coordinated locomotion abilities
      as a symptom. The mice used were 36 heterozygotes (12 females) and 50 knockout
      mice (30 females) at the age of 6 months. The mice were placed one at a time into
      the test setup, which consisted of a Plexiglas cage (53x34.5x26 cm) and two
      fluorescent bulbs for proper illumination. The transparent cage allowed images to
      be captured from underneath the cage, so image information could be obtained
      about the dynamic variation of the positions of the limbs of the mice for gait
      reconstruction. Every mouse was recorded for 10 min. Background subtraction and
      color filtering were used to measure and calculate image features, which are
      variables that contain crucial information, such as the mouse's position,
      orientation, body outline, and possible locations for the mouse's paws. A set of
      heuristic rules was used to prune implausible paw features and label the
      remaining ones as front/hind and left/right. After we had pruned the implausible
      paw features, the paw features that were consistent over subsequent images were
      matched to footprints. Finally, from the measured footprint sequence, eight
      parameters were calculated in order to quantify the gait of the mouse. This
      automatic observation technique can be integrated with a regular open-field test,
      where the trajectory and motor function of a free-moving mouse are measured
      simultaneously.

PMID- 19587196
TI  - A simple method for measuring brain asymmetry in children: application to autism.
AB  - A device for measuring signal transfer within and between hemispheres has been
      developed at the Center for Neuropsychological Research at the University of
      Trier, Germany. It contains two identical panels allowing both tactile
      stimulation and motor response with buttons for the fingers of each hand. The
      buttons have two functions. They can exert a slight tactile stimulation to a
      finger, and they can be pressed down by the finger to provide a motor response to
      the tactile stimulation allowing measuring the response time. The device was used
      for measuring brain asymmetry in tactile processing autistic children. The
      participants were given a finger tapping test followed by the procedures with
      unilateral and bilateral processing of tactile stimulation. All participants
      responded positively to the test procedure and accepted it as a kind of game. The
      results indicated that brains were more asymmetrical in autistic children than in
      controls: The right hemisphere functioned quicker than the left hemisphere.

PMID- 19587195
TI  - The inhibitory avoidance test optimized for discovery of cognitive enhancers.
AB  - In the present article, we describe a new protocol for the inhibitory avoidance
      test, with a dual purpose: (1) to provide a less variable and more reliable
      assessment of the efficacy of potential cognitive enhancers in antagonizing
      scopolamine-induced long-term-memory deficits, and (2) to secure a high
      throughput for pharmacological screening of cognitive enhancers. The new protocol
      consists of two acquisition trials that are followed 24 h later by a single
      retention trial. In the present study, this protocol clearly dissociated the
      frequency distributions of retention latencies between scopolamine- and vehicle
      treated groups and allowed validation by means of two acetylcholinesterase
      inhibitors-tacrine and donepezil-that proved to be active in counteracting the
      scopolamine-induced memory deficit. This protocol also produced stability of the
      behavioral response to pharmacological agents over a 3-year period. A statistical
      power analysis indicated that, depending on the efficacy of the drug/dose, a
      sample size of 5-12 mice was required in order to show a reversal of the
      scopolamine-induced memory deficit. The double-trial acquisition protocol is
      suitable for testing cognitive enhancers, while also providing a clearly enhanced
      throughput.

PMID- 19587197
TI  - Reading the tea leaves in an intelligent Coffee Corner: challenges for
      understanding behavior.
AB  - This article discusses the challenges for methodological innovation on the basis
      of experiences in an experimental Living Lab setting: a context-aware Coffee
      Corner in a research institute. A context-aware infrastructure collects sensory
      information on users while they move and interact. People getting coffee can use
      a variety of services offered in the intelligent environment at the Coffee
      Corner's site; for example, a colleague-radar application allows users to see the
      current positions of their colleagues in the building. At the same time, it
      identifies and authenticates users using proximity-aware and context-aware
      security features. Apart from proximity and context awareness, the analysis of
      contextual data allows the construction of a behavioral model of users that can
      be used to customize the services offered at the Coffee Corner. We explain how
      the Living Lab allows us to measure behavior in context in an unobtrusive and
      trustworthy way (e.g., by respecting a user's right to privacy).

PMID- 19587198
TI  - A wireless portable physiology recorder for psychophysiology research based on a
      personal digital assistant.
AB  - Psychophysiology research is increasingly relying on portable instruments that
      can assess physiological responses during real-life situations at locations
      outside of research labs, such as at school, home, work, and outdoors. In this
      article, I report on the feasibility of a personal digital assistant-based
      portable physiology recording system with online signal graphing and wireless
      digital telemetry for psychophysiology research. I demonstrate that such a system
      can measure electrocardiogram and electrodermal activity and send this data over
      a wireless communication link to a PC. It enables users to inspect the integrity
      of the acquired signals on the portable device and on a PC base station, and it
      allows users to place time markers for online data analysis.

PMID- 19587199
TI  - Using Noldus Observer XT for research on deaf signers learning to read: an
      innovative methodology.
AB  - Despite years of research on the reading problems of deaf students, we still do
      not know how deaf signers who read well actually crack the code of print. How
      connections are made between sign language and written language is still an open
      question. In this article, we show how the Noldus Observer XT software can be
      used to conduct an in-depth analysis of the online behavior of deaf readers.
      First, we examine factors that may have an impact on reading behavior. Then, we
      describe how we videotaped teachers with their deaf student signers of langue des
      signes quebecoise during a reading task, how we conducted a recall activity to
      better understand the students' reading behavior, and how we used this innovative
      software to analyze the taped footage. Finally, we discuss the contribution this
      type of research can have on the future reading behavior of deaf students.

PMID- 19587200
TI  - Coding gestural behavior with the NEUROGES--ELAN system.
AB  - We present a coding system combined with an annotation tool for the analysis of
      gestural behavior. The NEUROGES coding system consists of three modules that
      progress from gesture kinetics to gesture function. Grounded on empirical
      neuropsychological and psychological studies, the theoretical assumption behind
      NEUROGES is that its main kinetic and functional movement categories are
      differentially associated with specific cognitive, emotional, and interactive
      functions. ELAN is a free, multimodal annotation tool for digital audio and video
      media. It supports multileveled transcription and complies with such standards as
      XML and Unicode. ELAN allows gesture categories to be stored with associated
      vocabularies that are reusable by means of template files. The combination of the
      NEUROGES coding system and the annotation tool ELAN creates an effective tool for
      empirical research on gestural behavior.

PMID- 19587201
TI  - Behavioral phenotyping of a murine model of Alzheimer's disease in a
      seminaturalistic environment using RFID tracking.
AB  - Neurodegenerative disorders such as Alzheimer's disease (AD) are increasingly
      threatening public health. Most animal models of AD consist of transgenic mice
      that are usually housed singly or in unisexual groups in small barren cages. Such
      restricted environments, however, prevent the mice from showing a variety of
      species-specific behaviors and consequently may constrain comprehensive
      behavioral phenotyping. On the other hand, allowing the animals to freely
      organize their lives in a spacious physically and socially enriched environment
      makes behavioral phenotyping laborious and time consuming. Radio frequency
      identification (RFID) using a network of antennae and small glass-coated
      transponders labeling each individual allows for gathering spatiotemporal
      information about a large number of individuals in parallel. The aim of this
      project was to use the RFID technique to facilitate the characterization of mice
      carrying a genetic disposition to develop AD-like pathology and of their wild
      type conspecifics in a spacious seminaturalistic environment.

PMID- 19587202
TI  - Identifying and analyzing motor skill responses in body movement and dance.
AB  - The present article analyzes the diversity of motor skills related to three
      different kinds of instructions: descriptive, metaphoric, and kinesic, with a
      special emphasis on the detection of temporal patterns (T-patterns). Twelve
      undergraduates studying sport and physical education, but without experience in
      dance, were observed during 24 lessons of Body Movement, a discipline based on
      creative dance, mime dance, and motor skill improvisation. Using observational
      methodology and technology applied to movement, the aim of this article was to
      adapt the Observational instrument of Motor Skills (OSMOS) (Castaner, Torrents,
      Anguera, & Dinusova, 2008) so as to create an instrument capable of analyzing the
      motor skill responses generated in lessons of Body Movement and Dance. The
      results, as reflected by the T-patterns detected, show that (1) participants try
      to generate their own motor skills but copy some fundamental components of the
      instructions, and (2) the criterion of stability in two configurations (support
      and axial) is the predominant category. Sequential and coordinated locomotion
      also appears to be very relevant.

PMID- 19587203
TI  - Exploring workload and attention measurements with uLog mouse data.
AB  - User-system interactions (e.g., mouse clicks and movements) can be logged with
      the uLog computer program. A Web-based study with 20 participants was conducted
      to investigate the feasibility of using uLog data as an indicator of workload and
      attention. Eye fixation, heart rate variability (HRV), and skin conductance were
      used to unveil users' workload and attention and, hence, to validate uLog data as
      indicators of these. Results on one of the Tasks did indeed show correlations
      between uLog data and HRV. This is a promising first step toward the validation
      of uLog mouse data as indicators of workload and attention.

PMID- 19587204
TI  - Epistemic action: a measure for cognitive support in tangible user interfaces?
AB  - The quality of user interfaces is often measured in terms of efficiency,
      effectiveness, and satisfaction. In the area of tangible user interfaces,
      epistemic--or exploratory--action has been suggested as a fourth measure of
      quality. In computer game studies (Kirsh & Maglio, 1992, 1994), players used
      epistemic actions to modify the environment, which helped them determine the
      correct position of blocks with less mental effort. There, the researchers found
      that it might be easier to physically modify the external world and then
      interpret it than to compute and interpret a new state mentally. Specifically,
      epistemic action may be a relevant concept when researching tangible user
      interfaces incorporating physical handles. This article examines the potential
      relations between the three traditional measures of usability and epistemic
      actions using three spatial planning tools with different degrees of physicality.
      The results indicate that epistemic action is a measure that is independent of
      the three traditional usability measures: efficiency, effectiveness, and
      satisfaction. However, epistemic action does not increase linearly with the
      physicality of a user interface, and it probably is a more complex measure that
      is also related to the reusability of the interface. Further research is needed
      to fully understand the potential of this measure.

PMID- 19587205
TI  - An integrated device to evaluate a driver's functional state.
AB  - In the field of cognitive ergonomics, research on car drivers requires multimodal
      in-vehicle systems for recording not only driving-related behavior, but also
      contextual information from their surroundings. In addition, reliable information
      concerning a driver's functional state should be obtained. In this article, we
      describe an integrated device simultaneously recording specific physiological
      data, video recordings of the driver and environment, parameters from the
      vehicle, and contextual data. Physiological signals from the autonomic nervous
      system provide objective and quantitative information on the driver's alertness
      and his/her ability to process specific driving-related stimuli or other
      nonspecific information. Consequently, recorded physiological responses can be
      related to individual driving events. Electrodermal and cardiac activities are
      sensitive to time-dependent variations in arousal level and to certain external
      stimuli, so there is great interest in studying drivers' behavior via measured
      physiological signals that have been established as suitable behavioral
      indicators. The present integrated device is capable of processing the relevant
      indices from raw measured data in real time.

PMID- 19587206
TI  - Similar but not the same: a comparison of the utility of directly rated and
      feature-based similarity measures for generating spatial models of conceptual
      data.
AB  - Spatial models are employed to represent conceptual data in a wide range of
      fields within psychological research. In order to generate spatial models, it is
      necessary to first obtain empirical similarity data. A number of methods are
      available for collecting these data, but little effort has been made to compare
      their relative utility. In this article, we compare directly rated and five
      feature-based similarity data types in regard to their ability to be adequately
      represented by a spatial model (representational goodness of fit), and the
      ability of the representations to predict three external empirical variables
      (predictive validity). The results indicate that the representational goodness of
      fit of the feature-based similarities is noticeably superior to the directly
      rated similarities, and that the predictions of representations derived from
      common feature similarity data are substantially more likely than the predictions
      of all of the alternative representations. It is suggested that these findings
      are highly relevant to researchers employing spatial models to represent
      conceptual data, given that direct pairwise ratings have generally been
      considered the "gold standard" means of obtaining empirical similarities.

PMID- 19587207
TI  - Nominal analysis of "variance".
AB  - Nominal responses are the natural way for people to report actions or opinions.
      Because nominal responses do not generate numerical data, they have been
      underutilized in behavioral research. On those occasions in which nominal
      responses are elicited, the responses are customarily aggregated over people or
      trials so that large-sample statistics can be employed. A new analysis is
      proposed that directly associates differences among responses with particular
      sources in factorial designs. A pair of nominal responses either matches or does
      not; when responses do not match, they vary. That analogue to variance is
      incorporated in the nominal analysis of "variance" (NANOVA) procedure, wherein
      the proportions of matches associated with sources play the same role as do sums
      of squares in an ANOVA. The NANOVA table is structured like an ANOVA table. The
      significance levels of the N ratios formed by comparing proportions are
      determined by resampling. Fictitious behavioral examples featuring independent
      groups and repeated measures designs are presented. A Windows program for the
      analysis is available.

PMID- 19587208
TI  - Estimating long-range dependence in time series: an evaluation of estimators
      implemented in R.
AB  - Recent studies have shown that many physiological and behavioral processes can be
      characterized by long-range correlations. The Hurst exponent H of fractal
      analysis and the fractional-differencing parameter d of the ARFIMA methodology
      are useful for capturing serial correlations. In this study, we report on
      different estimators of H and d implemented in R, a popular and freely available
      software package. By means of Monte Carlo simulations, we analyzed the
      performance of (1) the Geweke-Porter-Hudak estimator, (2) the approximate maximum
      likelihood algorithm, (3) the smoothed periodogram approach, (4) the Whittle
      estimator, (5) rescaled range analysis, (6) a modified periodogram, (7) Higuchi's
      method, and (8) detrended fluctuation analysis. The findings-confined to ARFIMA
      (0, d, 0) models and fractional Gaussian noise-identify the best estimators for
      persistent and antipersistent series. Two examples combining these results with
      the step-by-step procedure proposed by Delignieres et al. (2006) demonstrate how
      this evaluation can be used as a guideline in a typical research situation.

PMID- 19587209
TI  - Computational procedures for probing interactions in OLS and logistic regression:
      SPSS and SAS implementations.
AB  - Researchers often hypothesize moderated effects, in which the effect of an
      independent variable on an outcome variable depends on the value of a moderator
      variable. Such an effect reveals itself statistically as an interaction between
      the independent and moderator variables in a model of the outcome variable. When
      an interaction is found, it is important to probe the interaction, for theories
      and hypotheses often predict not just interaction but a specific pattern of
      effects of the focal independent variable as a function of the moderator. This
      article describes the familiar pick-a-point approach and the much less familiar
      Johnson-Neyman technique for probing interactions in linear models and introduces
      macros for SPSS and SAS to simplify the computations and facilitate the probing
      of interactions in ordinary least squares and logistic regression. A script
      version of the SPSS macro is also available for users who prefer a point-and
      click user interface rather than command syntax.

PMID- 19587210
TI  - Evaluating the two-component inspection model in a simplified luggage search
      task.
AB  - Visual inspection of X-ray images of luggage is a time-pressured task that
      typically shows large initial training effects, but there exists a paucity of
      models capable of evaluating performance and speed concurrently. In the present
      study, visual inspection ability during learning was modeled using Drury's two
      component inspection model (TCM; Drury, 1975) in a laboratory experiment
      involving 12 younger (mean age=20.8 years) and 12 older (mean age=60.0 years)
      naive participants undertaking a simplified luggage search task. Model fits and
      assumptions were found to be reliable and accurately reflected improvement with
      training for decision time, although neither search nor decision components of
      the model individually showed a significant effect of age. The decision component
      of the model showed larger improvement with training than did the search
      component, and stopping-time policy accurately reflected the improvements found
      between ages and within training levels. The TCM is a useful supplement to
      detection theory when speed of performance is a factor.

PMID- 19587211
TI  - New algorithms assessing short summaries in expository texts using latent
      semantic analysis.
AB  - In this study, we compared four expert graders with latent semantic analysis
      (LSA) to assess short summaries of an expository text. As is well known, there
      are technical difficulties for LSA to establish a good semantic representation
      when analyzing short texts. In order to improve the reliability of LSA relative
      to human graders, we analyzed three new algorithms by two holistic methods used
      in previous research (Leon, Olmos, Escudero, Canas, & Salmeron, 2006). The three
      new algorithms were (1) the semantic common network algorithm, an adaptation of
      an algorithm proposed by W. Kintsch (2001, 2002) with respect to LSA as a dynamic
      model of semantic representation; (2) a best-dimension reduction measure of the
      latent semantic space, selecting those dimensions that best contribute to
      improving the LSA assessment of summaries (Hu, Cai, Wiemer-Hastings, Graesser, &
      McNamara, 2007); and (3) the Euclidean distance measure, used by Rehder et al.
      (1998), which incorporates at the same time vector length and the cosine
      measures. A total of 192 Spanish middle-grade students and 6 experts took part in
      this study. They read an expository text and produced a short summary. Results
      showed significantly higher reliability of LSA as a computerized assessment tool
      for expository text when it used a best-dimension algorithm rather than a
      standard LSA algorithm. The semantic common network algorithm also showed
      promising results.

PMID- 19587213
TI  - Cooperation versus competition in a mass emergency evacuation: a new laboratory
      simulation and a new theoretical model.
AB  - Virtual reality technology is argued to be suitable to the simulation study of
      mass evacuation behavior, because of the practical and ethical constraints in
      researching this field. This article describes three studies in which a new
      virtual reality paradigm was used, in which participants had to escape from a
      burning underground rail station. Study 1 was carried out in an immersion
      laboratory and demonstrated that collective identification in the crowd was
      enhanced by the (shared) threat embodied in emergency itself. In Study 2, high
      identification participants were more helpful and pushed less than did low
      identification participants. In Study 3, identification and group size were
      experimentally manipulated, and similar results were obtained. These results
      support a hypothesis according to which (emergent) collective identity motivates
      solidarity with strangers. It is concluded that the virtual reality technology
      developed here represents a promising start, although more can be done to embed
      it in a traditional psychology laboratory setting.

PMID- 19587212
TI  - Selection-based virtual keyboard prototypes and data collection application.
AB  - An emerging area of research in engineering psychology is the evaluation of text
      entry for mobile devices using a small number of keys for the control of cursor
      direction and character selection from a matrix of characters (i.e., selection
      based data entry). The present article describes a software tool designed to
      reduce time and effort in the development of prototypes of alternative selection
      based text-entry schemes and their empirical evaluation. The tool, available for
      distribution to researchers, educators, and students, uses Action Script code
      compiled into an executable file that has an embedded Adobe Flash Player and is
      compatible with most operating systems (including Microsoft Windows, Apple OSX,
      and Linux).

PMID- 19587214
TI  - Rationalization of indigenous male circumcision as a sacred religious custom:
      health beliefs of Xhosa men in South Africa.
AB  - This article presents research findings based on the meaning of indigenous
      circumcision to Xhosa men in South Africa. In South Africa, male circumcision is
      a rite of passage from adolescence to adulthood. The country has experienced
      serious problems associated with the practice of this rite ranging from
      dehydration to death in the traditional "bush" circumcision schools. A
      qualitative, endogenous research DESIGN: "How do you experience having a son who
      is undergoing the circumcision rite?" The study revealed cultural circumcision as
      a "sacred religious practice" with five themes, namely (a) readiness of Xhosa
      families to engage in the circumcision ritual, (b) the act of circumcision and
      preparation for manhood, (c) the importance of symbolic purity during the
      circumcision ritual, (d) celebrating acquired manhood, and (5) aspects of manhood
      and the rejection of clinical care. Secondary to this are health promotion
      recommendations made for individuals involved in this ritual.

PMID- 19587215
TI  - Molecular bandages: inside-out, outside-in repair of cellular membranes. Focus on
      "Myoferlin is critical for endocytosis in endothelial cells".

PMID- 19587217
TI  - GLUT1-induced cFLIP expression promotes proliferation and prevents apoptosis in
      vascular smooth muscle cells.
AB  - Enhanced expression of the facilitative glucose transporter, GLUT1, has been
      shown to inhibit apoptosis in several cell systems including vascular smooth
      muscle cells (VSMCs). A decrease in apoptosis could lead to increased VSMC
      numbers in neointimal and medial arterial layers under several pathologic
      conditions. The hypothesis underlying these studies is that GLUT1 induces
      expression of antiapoptotic and prosurvival genes that increase VSMC survival.
      Transcriptomic analysis of A7r5 VSMCs, in which GLUT1 was acutely overexpressed,
      showed a 2.14-fold increase in c-FLICE inhibitory protein (cFLIP), which promotes
      cellular growth and prevents apoptosis through caspase 8 binding. We confirmed
      that overexpression of GLUT1 induced mRNA and protein expression of both the long
      and short isoforms of cFLIP (cFLIP(L) and cFLIP(S)) in primary and stable
      immortalized VSMC lines as well as in aortas from GLUT1 transgenic mice.
      Increased GLUT1 reduced VSMC death by more than twofold after serum withdrawal,
      as evidenced by decreased caspase 3 activity and Trypan blue exclusion studies.
      GLUT1 overexpression resulted in a greater than twofold increase in proliferating
      cell nuclear antigen expression and live cell numbers, consistent with augmented
      VSMC proliferation. Lentiviral knockdown of cFLIP(L) showed that cFLIP(L) was
      necessary for the proproliferative and antiapoptotic effects of GLUT1
      overexpression. Taken together, these data suggest that GLUT1 induction of
      cFLIP(L) expression augments proliferation and prevents apoptosis in VSMCs.

PMID- 19587216
TI  - Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial
      cells.
AB  - Atherogenesis involves activation of NF-kappaB in endothelial cells by fluid
      shear stress. Because this pathway involves integrins, we investigated the
      involvement of focal adhesion kinase (FAK). We found that FAK was not required
      for flow-stimulated translocation of the p65 NF-kappaB subunit to the nucleus but
      was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1,
      an NF-kappaB-dependent gene. NF-kappaB activation by TNF-alpha or hydrogen
      peroxide was FAK independent. Events upstream of NF-kappaB, including integrin
      activation, Rac activation, reactive oxygen production, and degradation of
      IkappaB, were FAK independent. FAK therefore regulates NF-kappaB phosphorylation
      and transcriptional activity in response to flow by a novel mechanism.

PMID- 19587219
TI  - Regulation of amino acid transporters by glucose and growth factors in cultured
      primary human trophoblast cells is mediated by mTOR signaling.
AB  - Inhibition of mammalian target of rapamycin (mTOR) signaling in cultured human
      primary trophoblast cells reduces the activity of key placental amino acid
      transporters. However, the upstream regulators of placental mTOR are unknown. We
      hypothesized that glucose, insulin, and IGF-I regulate placental amino acid
      transporters by inducing changes in mTOR signaling. Primary human trophoblast
      cells were cultured for 24 h with media containing various glucose
      concentrations, insulin, or IGF-I, with or without the mTOR inhibitor rapamycin,
      and, subsequently, the activity of system A, system L, and taurine (TAUT)
      transporters was measured. Glucose deprivation (0.5 mM glucose) did not
      significantly affect Thr172-AMP-activated protein kinase phosphorylation or REDD1
      expression but decreased S6 kinase 1 phosphorylation at Thr389. The activity of
      system L decreased in a dose-dependent manner in response to decreasing glucose
      concentrations. This effect was abolished in the presence of rapamycin. Glucose
      deprivation had two opposing effects on system A activity: 1) an "adaptive"
      upregulation mediated by an mTOR-independent mechanism and 2) downregulation by
      an mTOR-dependent mechanism. TAUT activity was increased after incubating cells
      with glucose-deprived media, and this effect was largely independent of mTOR
      signaling. Insulin and IGF-I increased system A activity and insulin stimulated
      system L activity, effects that were abolished by rapamycin. We conclude that the
      mTOR pathway represents an important intracellular regulatory link between
      nutrient and growth factor concentrations and amino acid transport in the human
      placenta.

PMID- 19587218
TI  - Metabolic inhibition increases activity of connexin-32 hemichannels permeable to
      Ca2+ in transfected HeLa cells.
AB  - Numerous cell types express functional connexin (Cx) hemichannels (HCs), and
      membrane depolarization and/or exposure to a divalent cation-free bathing
      solution (DCFS) have been shown to promote HC opening. However, little is known
      about conditions that can promote HC opening in the absence of strong
      depolarization and when extracellular divalent cation concentrations remain at
      physiological levels. Here the effects of metabolic inhibition (MI), an in vitro
      model of ischemia, on the activity of mouse Cx32 HCs were examined. In HeLa cells
      stably transfected with mouse Cx32 (HeLa-Cx32), MI induced an increase in
      cellular permeability to ethidium (Etd). The increase in Etd uptake was directly
      related to an increase in levels of Cx32 HCs present at the cell surface.
      Moreover, MI increased membrane currents in HeLa-Cx32 cells. Underlying these
      currents were channels exhibiting a unitary conductance of approximately 90 pS,
      consistent with Cx32 HCs. These currents and Etd uptake were blocked by HC
      inhibitors. The increase in Cx32 HC activity was preceded by a rapid reduction in
      mitochondrial membrane potential and a rise in free intracellular Ca(2+)
      concentration ([Ca(2+)](i)). The increase in free [Ca(2+)](i) was prevented by HC
      blockade or exposure to extracellular DCFS and was virtually absent in parental
      HeLa cells. Moreover, inhibition of Cx32 HCs expressed by HeLa cells in low
      confluence cultures drastically reduced cell death induced by oxygen-glucose
      deprivation, which is a more physiological model of ischemia-reperfusion. Thus HC
      blockade could reduce the increase in free [Ca(2+)](i) and cell death induced by
      ischemia-like conditions in cells expressing Cx32 HCs.

PMID- 19587220
TI  - Agonist-induced internalization and downregulation of gonadotropin-releasing
      hormone receptors.
AB  - Gonadotropin-releasing hormone (GnRH) acts via seven transmembrane receptors to
      stimulate gonadotropin secretion. Sustained stimulation desensitizes GnRH
      receptor (GnRHR)-mediated gonadotropin secretion, and this underlies agonist use
      in hormone-dependent cancers. Since type I mammalian GnRHR do not desensitize,
      agonist-induced internalization and downregulation may underlie desensitization
      of GnRH-stimulated gonadotropin secretion; however, research focus has recently
      shifted to anterograde trafficking, with the finding that human (h)GnRHR are
      mostly intracellular. Moreover, there is little direct evidence for agonist
      induced trafficking of hGnRHR, and whether or not type I mammalian GnRHR show
      agonist-induced internalization is controversial. Here we use automated imaging
      to monitor expression and internalization of hemagglutinin (HA)-tagged hGnRHRs,
      mouse (m) GnRHR, Xenopus (X) GnRHRs, and chimeric receptors (hGnRHR with added
      XGnRHR COOH tails, h.XGnRHR) expressed by adenoviral transduction in HeLa cells.
      We find that agonists stimulate downregulation and/or internalization of mGnRHR
      and XGnRHR, that GnRH stimulates trafficking of hGnRHR and can stimulate
      internalization or downregulation of hGnRHR when steps are taken to increase cell
      surface expression (addition of the XGnRHR COOH tail or pretreatment with
      pharmacological chaperone). Agonist effects on internalization (of h.XGnRHR) and
      downregulation (of hGnRHR and h.XGnRHR) were not mimicked by a peptide antagonist
      and were prevented by a mutation that prevents GnRHR signaling, demonstrating
      dependence on receptor signaling as well as agonist occupancy. Thus agonist
      induced internalization and downregulation of type I mammalian GnRHR occurs in
      HeLa cells, and we suggest that the high throughput imaging systems described
      here will facilitate study of the molecular mechanisms involved.

PMID- 19587221
TI  - Calcium homeostasis in human melanocytes: role of transient receptor potential
      melastatin 1 (TRPM1) and its regulation by ultraviolet light.
AB  - Transient receptor potential melastatin (TRPM) is a subfamily of ion channels
      that are involved in sensing taste, ambient temperature, low pH, osmolarity, and
      chemical ligands. Melastatin 1/TRPM1, the founding member, was originally
      identified as melanoma metastasis suppressor based on its expression in normal
      pigment cells in the skin and the eye but not in aggressive, metastasis-competent
      melanomas. The role of TRPM1 and its regulation in normal melanocytes and in
      melanoma progression is not understood. Here, we studied the relationship of
      TRPM1 expression to growth and differentiation of human epidermal melanocytes.
      TRPM1 expression and intracellular Ca(2+) levels are significantly lower in
      rapidly proliferating melanocytes compared to the slow growing, differentiated
      melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown
      of TRPM1 results in reduced intracellular Ca(2+) and decreased Ca(2+) uptake
      suggesting a role for TRPM1 in Ca(2+) homeostasis in melanocytes. TRPM1 knockdown
      also resulted in a decrease in tyrosinase activity and intracellular melanin
      pigment. Expression of the tumor suppressor p53 by transfection or induction of
      endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression
      accompanied by decrease in mobilization of intracellular Ca(2+) and uptake of
      extracellular Ca(2+). These data suggest a role for TRPM1-mediated Ca(2+)
      homeostasis, which is also regulated by ultraviolet B, in melanogenesis.

PMID- 19587222
TI  - PPARdelta-mediated p21/p27 induction via increased CREB-binding protein nuclear
      translocation in beraprost-induced antiproliferation of murine aortic smooth
      muscle cells.
AB  - We previously showed that an increase in the peroxisome proliferator-activated
      receptor-delta (PPARdelta), together with subsequent induction of inducible
      nitric oxide synthase (iNOS) by beraprost (BPS), inhibits aortic smooth muscle
      cell proliferation. Herein, we delineated the mechanisms of the antiproliferative
      effects of BPS through the induction of p21/p27. BPS concentration dependently
      induced the p21/p27 promoter- and consensus cAMP-responsive element (CRE)-driven
      luciferase activities, which were significantly suppressed by blocking PPARdelta
      activation. Surprisingly, other than altering the CRE-binding protein (CREB), BPS
      mediated PPARdelta activation increased nuclear localization of the CREB-binding
      protein (CBP), a coactivator, which was further confirmed by chromatin
      immunoprecipitation. Furthermore, novel functional PPAR-responsive elements
      (PPREs) next to CREs in the rat p21/p27 promoter regions were identified, where
      PPARdelta interacted with CREB through CBP recruitment. BPS-mediated suppression
      of restenosis in mice with angioplasty was associated with p21/p27 induction.
      Herein, we demonstrate for the first time that BPS-mediated PPARdelta activation
      enhances transcriptional activation of p21/p27 by increasing CBP nuclear
      translocation, which contributes to the vasoprotective action of BPS.

PMID- 19587223
TI  - Dose-related shortening of ventricular tachycardia cycle length after
      administration of the KATP channel opener bimakalim in a 4-day-old chronic
      infarct anesthetized pig model.
AB  - Potassium channel openers are known to act on potassium ATP-dependent channels in
      cardiac tissue. Such agents may exacerbate acceleration of acute ischemia-induced
      ventricular repolarization and aggravate arrhythmias. To test whether activation
      of K( ATP) channels during the healing period of myocardial infarction (MI) can
      still influence the electrophysiologic properties and the type of inducible
      arrhythmias, we investigated the effects of bimakalim (BIM) on sustained
      ventricular tachycardia (VT) 4 days after ligation of the left anterior
      descending (LAD) coronary artery in pigs. Programmed stimulation was performed to
      elicit VT prior to and after intravenous (IV) BIM. Combination monophasic action
      potential (MAP)/PACING catheters were used to enable simultaneous ventricular MAP
      recording and pacing. Ventricular effective refractory period (ERP) and MAP
      duration determined at 50% and 90% repolarization were measured prior to and
      after BIM. After completion of baseline measurements, BIM was consecutively given
      at 0.5, 1, and 3 mg/kg bolus followed by 0.025, 0.05, and 0.1 mg/kg per minute
      maintenance infusion, respectively. From a total of 23 pigs subjected to LAD
      ligation, 4 animals succumbed to infarction and the remaining 19 animals were
      studied by programmed stimulation. Only animals that exhibited reproducible and
      hemodynamically stable monomorphic VTs during control stimulation were selected
      for evaluation (n = 14). After the first, second, and third dose of BIM, the mean
      VT rate was increased by 6%, 14% (P <. 01), and 47% (P < .001) compared to
      control values, respectively. Ventricular ERP and repolarization were
      significantly shortened only by the second and third dose of BIM. Of 14 pigs
      receiving the highest BIM dosage, 3 revealed polymorphic VTs degenerating into
      ventricular fibrillation (VF). Our data suggest that high BIM doses may lead to
      faster and more aggressive pacing-induced reentrant VTs after subacute MI. This
      is consistent with the drug-induced acceleration of ventricular repolarization
      with shortening of MAP duration and refractoriness.

PMID- 19587224
TI  - ViTraM: visualization of transcriptional modules.
AB  - MOTIVATION: We developed ViTraM, a tool that allows visualizing overlapping
      transcriptional modules in an intuitive way. By visualizing not only the genes
      and the experiments in which the genes are co-expressed, but also additional
      properties of the modules such as the regulators and regulatory motifs that are
      responsible for the observed co-expression, ViTraM can assist in the biological
      analysis and interpretation of the output of module detection tools.
      AVAILABILITY: The ViTraM software is platform-independent. The software and
      supplementary material are available at:
      http://homes.esat.kuleuven.be/~kmarchal/ViTraM/Index.html

PMID- 19587225
TI  - Impact of the most frequent chronic health conditions on the quality of life
      among people aged >15 years in Madrid.
AB  - BACKGROUND: This study sought to ascertain to what degree health-related quality
      of life (HRQL) in the City of Madrid was affected by each of the most frequent
      chronic health conditions, and the specific quality-of-life (QL) domains on which
      such health conditions had the greatest impact, taking co-morbidity and socio
      demographic variables into account. METHODS: A descriptive, analytical, cross
      sectional study was conducted covering 7341 subjects aged >or=16 years in the
      City of Madrid. Data were collected on self-reported diagnosed morbidity,
      including hypertension, hypercholesterolaemia, varicose veins, diabetes, chronic
      asthma/bronchitis, myocardial infarction/angina pectoris, stomach problems,
      allergy, arthrosis/arthritis or rheumatism, depression/anxiety, cataracts,
      cerebrovascular accidents (CVACs), chronic constipation, osteoporosis and
      Alzheimer's disease or dementia. HRQL was measured using the COOP/WONCA
      questionnaire. The effects of diagnosis, age, social class, gender and the co
      morbidity were analysed using a multivariate analysis of covariance (ANCOVA).
      RESULTS: The chronic health conditions that registered the worst overall mean
      scores on the COOP/WONCA questionnaire were Alzheimer's disease or dementia,
      Parkinson's disease, fibromyalgia, CVACs and depression, with scores of over 26
      points in all cases. After the introduction of socio-demographic variables in the
      model, the highest values of Snedecor's F-test corresponds to depression (F =
      461.63), 'arthrosis/arthritis or rheumatism' (F = 175.41), Alzheimer's disease or
      dementia (F = 65.70), gastric disorders (F = 65.17), cancer (F = 43.08) and CVACs
      (F = 41.65). CONCLUSIONS: Depression and 'arthrosis/arthritis or rheumatism' are
      the two chronic health conditions, which have the greatest impact on HRQL in
      Madrid's citizens, therefore is mandatory to propose and implement public health
      strategies that would reduce the prevalence and morbidity of such disorders.

PMID- 19587226
TI  - The prevalence of sedentary behaviours and physical activity in Hungarian youth.
AB  - BACKGROUND: The study of sedentary behaviour is becoming much more visible,
      alongside research on physical activity. Few published studies, however,
      originate from Eastern or Central Europe. METHOD: Prevalence and point estimate
      data of key leisure time sedentary and active behaviours are reported from
      Hungary, a country that has been through an important political transition in the
      past two decades. Participants (n = 301) aged 13-18 years completed time-use
      diaries over 4 days for time outside of school. Sedentary and active behaviours
      were coded and analysed. RESULTS: TV viewing reflected trends found elsewhere and
      was the most prevalent sedentary behaviour. Physical activity levels were low.
      The next most time-consuming sedentary weekday activities were homework,
      motorized transport, sitting and talking and playing computer/video games. Gender
      differences were different to some other countries, with girls reporting more
      computer game use and boys more sitting and talking, but these may reflect
      cultural and reporting differences. CONCLUSION: This study provides the first
      comprehensive description of sedentary behavioural prevalence in Hungarian youth.

PMID- 19587227
TI  - Is bullying equally harmful for rich and poor children?: a study of bullying and
      depression from age 15 to 27.
AB  - BACKGROUND: Exposure to bullying in childhood and adolescence is harmful to
      health, well-being and social competence of the victim. However, little is known
      about the long-term consequences of bullying victimization. In this paper, we use
      a longitudinal study from age 15 to 27 to examine whether childhood socioeconomic
      position (CSP) modifies the association between exposure to bullying in childhood
      and symptoms of depression in young adulthood. METHODS: Nationally representative
      baseline sample in 1990 (n = 847), followed up 2002 (n = 614). We used
      multivariate analyses of variance to examine the influence of bullying on
      symptoms of depression at age 27. RESULTS: Analyses showed that exposure to
      bullying, low CSP and female gender significantly increased the risk of
      depression in young adulthood. There was a statistically significant interaction
      between bullying and CSP, so that bullying increased the risk of depression for
      people from low CSP, while there was only a weak association between bullying
      victimization and depressive symptoms for people from more affluent childhood
      socioeconomic backgrounds. The same pattern was found for analyses stratified by
      sex. CONCLUSION: Our study suggests that the effects of bullying may have more
      serious long-term implications on health for children from less affluent
      backgrounds. Our study points at bullying exposure as another pathway through
      which social adversity in childhood influences social inequalities in adult
      health. Political efforts are needed to improve norms and legislations about how
      to treat children and more specific interventions should take place in schools to
      reduce the exposure to bullying.

PMID- 19587228
TI  - Too early to stop immigrant vaccination programmes.

PMID- 19587229
TI  - Causality, social selectivity or artefacts? Why socioeconomic inequalities in
      health are not smallest in the Nordic countries.

PMID- 19587230
TI  - Living longer and feeling better: healthy lifestyle, self-rated health, obesity
      and depression in Ireland.
AB  - BACKGROUND: The combination of four protective lifestyle behaviours (being
      physically active, a non-smoker, a moderate alcohol consumer and having adequate
      fruit and vegetable intake) has been estimated to increase life expectancy by 14
      years. However, the effect of adopting these lifestyle behaviours on general
      health, obesity and mental health is less defined. We examined the combined
      effect of these behaviours on self-rated health, overweight/obesity and
      depression. METHODS: Using data from the Survey of Lifestyle Attitudes and
      Nutrition (SLAN) 2007 (), a protective lifestyle behaviour (PLB) score was
      constructed for 10,364 men and women (>18 years), and representative of the
      Republic of Ireland adult population (response rate 62%). Respondents scored a
      maximum of four points, one point each for being physically active, consuming
      five or more fruit and vegetable servings daily, a non-smoker and a moderate
      drinker. RESULTS: One-fifth of respondents (20%) adopted four PLBs, 35% adopted
      three, 29% two, 13% one and 2% adopted none. Compared to those with zero PLBs,
      those with four were seven times more likely to rate their general health as
      excellent/very good [OR 6.8 95% CI (3.64-12.82)] and four times more likely to
      have better mental health [OR 4.4 95% CI (2.34-8.22)]. CONCLUSIONS: Adoption of
      core protective lifestyle factors known to increase life expectancy is associated
      with positive self-rated health, healthier weight and better mental health. These
      lifestyles have the potential to add quality and quantity to life.

PMID- 19587231
TI  - Diabetes prevalence and risk factors among ethnic minorities.
AB  - BACKGROUND: Ethnic minorities living in Western societies may have a higher
      prevalence of diabetes. We investigated whether the prevalence of diabetes among
      Turkish and Moroccan migrants differs from the indigenous urban population in the
      Netherlands, and whether these differences can be explained by differences in
      risk factors. METHODS: In 2004 a general health survey, stratified by ethnicity
      and age, was carried out among the population of Amsterdam. The current study
      included 375 Turkish, 314 Moroccan and 417 Dutch individuals aged 18-70 years.
      Participants underwent a physical examination and a health interview. Diabetes
      was based on self-report, the use of anti-diabetic medicine, blood glucose levels
      and HbA1c. RESULTS: The prevalence of diabetes in the Amsterdam population was
      significantly higher in Turkish (5.6%) and Moroccan (8.0%), compared to Dutch
      individuals (3.1%). These differences, which were much larger after adjustment
      for age, were only partly explained by the lower socioeconomic status and higher
      frequency of obesity among ethnic minorities. The difference between Dutch and
      Moroccan individuals remained significant even after adjustments for multiple
      risk factors. The typical age of onset of diabetes in both Turks and Moroccans is
      respectively one and two decades younger than in the indigenous population.
      CONCLUSION: Diabetes is more prevalent among Turkish and Moroccan migrants as
      compared to the indigenous population. Only part of this difference can be
      explained by differences in demographic and lifestyle risk factors.

PMID- 19587232
TI  - Value for money or making the healthy choice: the impact of proportional pricing
      on consumers' portion size choices.
AB  - BACKGROUND: Large food portion sizes are determinants of a high caloric intake,
      especially if they have been made attractive through value size pricing (i.e.
      lower unit prices for large than for small portion sizes). The purpose of the two
      questionnaire studies that are reported in this article was to assess the impact
      of proportional pricing (i.e. removing beneficial prices for large sizes) on
      people's portion size choices of high caloric food and drink items. METHODS: Both
      studies employed an experimental design with a proportional pricing condition and
      a value size pricing condition. Study 1 was conducted in a fast food restaurant
      (N = 150) and study 2 in a worksite cafeteria (N = 141). Three different food
      products (i.e. soft drink, chicken nuggets in study 1 and a hot meal in study 2)
      with corresponding prices were displayed on pictures in the questionnaire.
      Outcome measures were consumers' intended portion size choices. RESULTS: No main
      effects of pricing were found. However, confronted with proportional pricing a
      trend was found for overweight fast food restaurant visitors being more likely to
      choose small portion sizes of chicken nuggets (OR = 4.31, P = 0.07) and less
      likely to choose large soft drink sizes (OR = 0.07, P = 0.04). CONCLUSION: Among
      a general public, proportional pricing did not reduce consumers' size choices.
      However, pricing strategies can help overweight and obese consumers selecting
      appropriate portion sizes of soft drink and high caloric snacks. More research in
      realistic settings with actual behaviour as outcome measure is required.

PMID- 19587233
TI  - Belief in complementary and alternative medicine is related to age and paranormal
      beliefs in adults.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is
      widespread, even among people who use conventional medicine. Positive beliefs
      about CAM are common among physicians and medical students. Little is known about
      the beliefs regarding CAM among the general public. Among science students,
      belief in CAM was predicted by belief in the paranormal. METHODS: In a cross
      sectional study, 712 randomly selected adults (>18 years old) responded to the
      CAM Health Belief Questionnaire (CHBQ) and a paranormal beliefs scale. RESULTS:
      CAM beliefs were very prevalent in this sample of adult Flemish men and women.
      Zero-order correlations indicated that belief in CAM was associated with age (r =
      0.173 P < 0.001) level of education (r = -0.079 P = 0.039) social desirability (r
      = -0.119 P = 0.002) and paranormal belief (r = 0.365 P < 0.001). In a
      multivariate model, two variables predicted CAM beliefs. Support for CAM
      increased with age (regression coefficient: 0.01; 95% confidence interval (CI):
      0.006 to 0.014), but the strongest relationship existed between support for CAM
      and beliefs in the paranormal. Paranormal beliefs accounted for 14% of the
      variance of the CAM beliefs (regression coefficient: 0.376; 95%: CI 0.30-0.44).
      The level of education (regression coefficient: 0.06; 95% CI: -0.014-0.129) and
      social desirability (regression coefficient: -0.023; 95% CI: -0.048-0.026) did
      not make a significant contribution to the explained variance (<0.1%, P = 0.867).
      CONCLUSION: Support of CAM was very prevalent in this Flemish adult population.
      CAM beliefs were strongly associated with paranormal beliefs.

PMID- 19587234
TI  - Structure of human Rad51 protein filament from molecular modeling and site
      specific linear dichroism spectroscopy.
AB  - To get mechanistic insight into the DNA strand-exchange reaction of homologous
      recombination, we solved a filament structure of a human Rad51 protein, combining
      molecular modeling with experimental data. We build our structure on reported
      structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein
      by aid of linear dichroism spectroscopy, providing angular orientations of
      substituted tyrosine residues of Rad51-dsDNA filaments in solution. The
      structure, validated by comparison with an electron microscopy density map and
      results from mutation analysis, is proposed to represent an active solution
      structure of the nucleo-protein complex. An inhomogeneously stretched double
      stranded DNA fitted into the filament emphasizes the strategic positioning of 2
      putative DNA-binding loops in a way that allows us speculate about their possibly
      distinct roles in nucleo-protein filament assembly and DNA strand-exchange
      reaction. The model suggests that the extension of a single-stranded DNA molecule
      upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop,
      which might act as a docking tool, aligning protein monomers along the DNA strand
      upon filament assembly. Arg-235, also sitting on L1, is in the right position to
      make electrostatic contact with the phosphate backbone of the other DNA strand.
      The L2 loop position and its more ordered compact conformation makes us propose
      that this loop has another role, as a binding site for an incoming double
      stranded DNA. Our filament structure and spectroscopic approach open the
      possibility of analyzing details along the multistep path of the strand-exchange
      reaction.

PMID- 19587235
TI  - Tumor suppressor function of laminin-binding alpha-dystroglycan requires a
      distinct beta3-N-acetylglucosaminyltransferase.
AB  - Alpha-dystroglycan (alpha-DG) represents a highly glycosylated cell surface
      molecule that is expressed in the epithelial cell-basement membrane (BM)
      interface and plays an essential role in epithelium development and tissue
      organization. The alpha-DG-mediated epithelial cell-BM interaction is often
      impaired in invasive carcinomas, yet roles and underlying mechanisms of such an
      impaired interaction in tumor progression remain unclear. We report here a
      suppressor function of laminin-binding glycans on alpha-DG in tumor progression.
      In aggressive prostate and breast carcinoma cell lines, laminin-binding glycans
      are dramatically decreased, although the amount of alpha-DG and beta-dystroglycan
      is maintained. The decrease of laminin-binding glycans and consequent increased
      cell migration were associated with the decreased expression of beta3-N
      acetylglucosaminyltransferase-1 (beta3GnT1). Forced expression of beta3GnT1 in
      aggressive cancer cells restored the laminin-binding glycans and decreased tumor
      formation. beta3GnT1 was found to be required for laminin-binding glycan
      synthesis through formation of a complex with LARGE, thus regulating the function
      of LARGE. Interaction of the laminin-binding glycans with laminin and other
      adhesive molecules in BM attenuates tumor cell migratory potential by
      antagonizing ERK/AKT phosphorylation induced by the components in the ECM. These
      results identify a previously undescribed role of carbohydrate-dependent cell-BM
      interaction in tumor suppression and its control by beta3GnT1 and LARGE.

PMID- 19587236
TI  - Accelerating loss of seagrasses across the globe threatens coastal ecosystems.
AB  - Coastal ecosystems and the services they provide are adversely affected by a wide
      variety of human activities. In particular, seagrass meadows are negatively
      affected by impacts accruing from the billion or more people who live within 50
      km of them. Seagrass meadows provide important ecosystem services, including an
      estimated $1.9 trillion per year in the form of nutrient cycling; an order of
      magnitude enhancement of coral reef fish productivity; a habitat for thousands of
      fish, bird, and invertebrate species; and a major food source for endangered
      dugong, manatee, and green turtle. Although individual impacts from coastal
      development, degraded water quality, and climate change have been documented,
      there has been no quantitative global assessment of seagrass loss until now. Our
      comprehensive global assessment of 215 studies found that seagrasses have been
      disappearing at a rate of 110 km(2) yr(-1) since 1980 and that 29% of the known
      areal extent has disappeared since seagrass areas were initially recorded in
      1879. Furthermore, rates of decline have accelerated from a median of 0.9% yr(-1)
      before 1940 to 7% yr(-1) since 1990. Seagrass loss rates are comparable to those
      reported for mangroves, coral reefs, and tropical rainforests and place seagrass
      meadows among the most threatened ecosystems on earth.

PMID- 19587237
TI  - Zinc chlorins for artificial light-harvesting self-assemble into antiparallel
      stacks forming a microcrystalline solid-state material.
AB  - We introduce a concept to solve the structure of a microcrystalline material in
      the solid-state at natural abundance without access to distance constraints,
      using magic angle spinning (MAS) NMR spectroscopy in conjunction with X-ray
      powder diffraction and DFT calculations. The method is applied to a novel class
      of materials that form (semi)conductive 1D wires for supramolecular electronics
      and artificial light-harvesting. The zinc chlorins 3-devinyl-3(1)-hydroxymethyl
      13(2)-demethoxycarbonylpheophorbide a (3',5'-bis-dodecyloxy)benzyl ester zinc
      complex 1 and 3-devinyl-3(1)-methoxymethyl-13(2)-demethoxycarbonylpheophorbide a
      (3',5'-bis-dodecyloxy)benzyl ester zinc complex 2, self-assemble into extended
      excitonically coupled chromophore stacks. (1)H-(13)C heteronuclear dipolar
      correlation MAS NMR experiments provided the (1)H resonance assignment of the
      chlorin rings that allowed accurate probing of ring currents related to the
      stacking of macrocycles. DFT ring-current shift calculations revealed that both
      chlorins self-assemble in antiparallel pi-stacks in planar layers in the solid
      state. Concomitantly, X-ray powder diffraction measurements for chlorin 2 at 80
      degrees C revealed a 3D lattice for the mesoscale packing that matches molecular
      mechanics optimized aggregate models. For chlorin 2 the stacks alternate with a
      periodicity of 0.68 nm and a 3D unit cell with an approximate volume of 6.28
      nm(3) containing 4 molecules, which is consistent with space group P2(1)22(1).

PMID- 19587238
TI  - Intracellular activation of vasopressin V2 receptor mutants in nephrogenic
      diabetes insipidus by nonpeptide agonists.
AB  - Binding of the peptide hormone vasopressin to its type-2 receptor (V2R) in kidney
      triggers a cAMP-mediated translocation of Aquaporin-2 water channels to the
      apical membrane, resulting in water reabsorption and thereby preventing
      dehydration. Mutations in the V2R gene lead to Nephrogenic Diabetes Insipidus
      (NDI), a disorder in which this process is disturbed, because the encoded, often
      intrinsically functional mutant V2 receptors are misfolded and retained in the
      endoplasmic reticulum (ER). Since plasma membrane expression is thought to be
      essential for V2R activation, cell permeable V2R antagonists have been used to
      induce maturation and rescue cell surface expression of V2R mutants, after which
      they need to be displaced by vasopressin for activation. Here, however, we show
      that 3 novel nonpeptide V2R agonists, but not vasopressin, activate NDI-causing
      V2R mutants at their intracellular location, without changing their maturation
      and at a sufficient level to induce the translocation of aquaporin-2 to the
      apical membrane. Moreover, in contrast to plasma membrane V2R, degradation of
      intracellular V2R mutants is not increased by their activation. Our data reveal
      that G protein-coupled receptors (GPCRs) normally active at the plasma membrane
      can be activated intracellularly and that intracellular activation does not
      induce their degradation; the data also indicate that nonpeptide agonists
      constitute highly promising therapeutics for diseases caused by misfolded GPCRs
      in general, and NDI in particular.

PMID- 19587239
TI  - MAP4K3 modulates cell death via the post-transcriptional regulation of BH3-only
      proteins.
AB  - Intracellular signal transduction networks involving protein kinases are
      important modulators of cell survival and cell death in multicellular organisms.
      Functional compromise of these networks has been linked to aberrant apoptosis in
      diseases such as cancer. To identify novel kinase regulators of cell death, we
      conducted an RNAi-based screen to identify modulators of the intrinsic apoptosis
      pathway. Using this approach, we identified MAP4K3 as a novel apoptosis inducer.
      Here, we present evidence that this pro-apoptotic kinase orchestrates activation
      of BAX via the concerted posttranscriptional modulation of PUMA, BAD, and BIM.
      Additionally, we found decreased levels of this kinase in pancreatic cancer
      samples, suggesting a tumor suppressor role for MAP4K3 in pancreatic
      tumorigenesis.

PMID- 19587240
TI  - Polysialic acid governs T-cell development by regulating progenitor access to the
      thymus.
AB  - Although the polysialyltransferase ST8Sia IV is expressed in both primary and
      secondary human lymphoid organs, its product, polysialic acid (polySia), has been
      largely overlooked by immunologists. In contrast, polySia expression and function
      in the nervous system has been well characterized. In this context, polySia
      modulates cellular adhesion, migration, cytokine response, and contact-dependent
      differentiation. Provocatively, these same processes are vital components of
      immune development and function. We previously established that mouse multipotent
      hematopoietic progenitors use ST8Sia IV to express polySia on their cell
      surfaces. Here, we demonstrate that, relative to wild-type controls, ST8Sia IV(-/
      ) mice have a 30% reduction in total thymocytes and a concomitant deficiency in
      the earliest thymocyte precursors. T-cell progenitors originate in the bone
      marrow and are mobilized to the blood at regular intervals by unknown signals. We
      performed in vivo reconstitution experiments in which ST8Sia IV(-/-) progenitors
      competed with wild-type cells to repopulate depleted or deficient immune subsets.
      Progenitors lacking polySi exhibited a specific defect in T-cell development
      because of an inability to access the thymus. This phenotype probably reflects a
      decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone
      marrow niche. Collectively, these results provide evidence that polySia is
      involved in hematopoietic development.

PMID- 19587241
TI  - Interactions between mutualist Wigglesworthia and tsetse peptidoglycan
      recognition protein (PGRP-LB) influence trypanosome transmission.
AB  - Tsetse flies, the sole vectors of African trypanosomes, have coevolved with
      mutualistic endosymbiont Wigglesworthia glossinidiae. Elimination of
      Wigglesworthia renders tsetse sterile and increases their trypanosome infection
      susceptibility. We show that a tsetse peptidoglycan recognition protein (PGRP-LB)
      is crucial for symbiotic tolerance and trypanosome infection processes. Tsetse
      pgrp-lb is expressed in the Wigglesworthia-harboring organ (bacteriome) in the
      midgut, and its level of expression correlates with symbiont numbers. Adult
      tsetse cured of Wigglesworthia infections have significantly lower pgrp-lb levels
      than corresponding normal adults. RNA interference (RNAi)-mediated depletion of
      pgrp-lb results in the activation of the immune deficiency (IMD) signaling
      pathway and leads to the synthesis of antimicrobial peptides (AMPs), which
      decrease Wigglesworthia density. Depletion of pgrp-lb also increases the host's
      susceptibility to trypanosome infections. Finally, parasitized adults have
      significantly lower pgrp-lb levels than flies, which have successfully eliminated
      trypanosome infections. When both PGRP-LB and IMD immunity pathway functions are
      blocked, flies become unusually susceptible to parasitism. Based on the presence
      of conserved amidase domains, tsetse PGRP-LB may scavenge the peptidoglycan (PGN)
      released by Wigglesworthia and prevent the activation of symbiont-damaging host
      immune responses. In addition, tsetse PGRP-LB may have an anti-protozoal activity
      that confers parasite resistance. The symbiotic adaptations and the limited
      exposure of tsetse to foreign microbes may have led to the considerable
      differences in pgrp-lb expression and regulation noted in tsetse from that of
      closely related Drosophila. A dynamic interplay between Wigglesworthia and host
      immunity apparently is influential in tsetse's ability to transmit trypanosomes.

PMID- 19587242
TI  - Stepwise acquisition of pyrimethamine resistance in the malaria parasite.
AB  - The spread of high-level pyrimethamine resistance in Africa threatens to curtail
      the therapeutic lifetime of antifolate antimalarials. We studied the possible
      evolutionary pathways in the evolution of pyrimethamine resistance using an
      approach in which all possible mutational intermediates were created by site
      directed mutagenesis and assayed for their level of drug resistance. The coding
      sequence for dihydrofolate reductase (DHFR) from the malaria parasite Plasmodium
      falciparum was mutagenized, and tests were carried out in Escherichia coli under
      conditions in which the endogenous bacterial enzyme was selectively inhibited. We
      studied 4 key amino acid replacements implicated in pyrimethamine resistance:
      N51I, C59R, S108N, and I164L. Using empirical estimates of the mutational
      spectrum in P. falciparum and probabilities of fixation based on the relative
      levels of resistance, we found that the predicted favored pathways of drug
      resistance are consistent with those reported in previous kinetic studies, as
      well as DHFR polymorphisms observed in natural populations. We found that 3
      pathways account for nearly 90% of the simulated realizations of the evolution of
      pyrimethamine resistance. The most frequent pathway (S108N and then C59R, N51I,
      and I164L) accounts for more than half of the simulated realizations. Our results
      also suggest an explanation for why I164L is detected in Southeast Asia and South
      America, but not at significant frequencies in Africa.

PMID- 19587244
TI  - Fourth journal of the American Board of Family Medicine practice-based research
      theme issue.

PMID- 19587243
TI  - Fasting hyperglycemia is not associated with increased expression of PEPCK or
      G6Pc in patients with Type 2 Diabetes.
AB  - Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is
      attributed to increased hepatic gluconeogenesis, which has been ascribed to
      increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK)
      and glucose-6-phosphatase, catalytic (G6Pc). To test this hypothesis, we examined
      hepatic expression of these 2 key gluconeogenic enzymes in 2 rodent models of
      fasting hyperglycemia and in patients with T2DM. In rats, high-fat feeding (HFF)
      induces insulin resistance but a robust beta-cell response prevents
      hyperglycemia. Fasting hyperglycemia was induced in the first rat model by using
      nicotinamide and streptozotocin to prevent beta-cell compensation, in combination
      with HFF (STZ/HFF). In a second model, control and HFF rats were infused with
      somatostatin, followed by portal vein infusion of insulin and glucagon. Finally,
      the expression of these enzymes was measured in liver biopsy samples obtained
      from insulin sensitive, insulin resistant, and untreated T2DM patients undergoing
      bariatric surgery. Rats treated with STZ/HFF developed modest fasting
      hyperglycemia (119 +/- 4 vs. 153 +/- 6 mg/dL, P < 0.001) and increased rates of
      endogenous glucose production (EGP) (4.6 +/- 0.6 vs. 6.9 +/- 0.6 mg/kg/min, P =
      0.02). Surprisingly, the expression of PEPCK or G6Pc was not increased. Matching
      plasma insulin and glucagon with portal infusions led to higher plasma glucoses
      in the HFF rats (147 +/- 4 vs. 161 +/- 4 mg/dL, P = 0.05) with higher rates of
      EGP and gluconeogenesis. However, PEPCK and G6Pc expression remained unchanged.
      Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not
      increased. Thus, in contrast to current dogma, these data demonstrate that
      increased transcriptional expression of PEPCK1 and G6Pc does not account for
      increased gluconeogenesis and fasting hyperglycemia in patients with T2DM.

PMID- 19587246
TI  - Increasing the role of practice networks in medical research.

PMID- 19587248
TI  - Assessing the impact on patient-physician interaction when physicians use
      personal digital assistants: a Northeastern Ohio Network (NEON) study.
AB  - BACKGROUND: The effects of the use of technological devices on dimensions that
      affect the physician-patient relationship need to be well understood. OBJECTIVES:
      Determine patients' perceptions of physicians' personal digital assistant (PDA)
      use, comparing the results across 8 physician-patient dimensions important to
      clinical interactions. RESULTS: Patients completed anonymous surveys about their
      perceptions of physician PDA use. Data were collected during 2006 and 2007 at 12
      family medicine practices. Survey items included physician sex, patient
      demographics, if physicians explained why they were using the PDA, and Likert
      ratings on 8 dimensions of how a PDA can influence physician-patient interactions
      (surprise, confidence, feelings, comfort, communication, relationship,
      intelligence, and satisfaction). The survey response rate was 78%. Physicians
      explained to their patients what they were doing with the PDA 64% of the time.
      Logistic regression analyses determined that patients of male physicians,
      patients attending private practices and underserved sites, patients with
      Medicaid insurance, and patients who observed their physician using a PDA during
      both the index visit and at least one prior visit were more likely to receive an
      explanation of PDA use. Most importantly, physician-patient communication was
      rated significantly more positive if an explanation of PDA use was offered.
      CONCLUSION: Patients rate interactions with their physicians more positively when
      physicians explain their PDA use.

PMID- 19587249
TI  - Interventions to improving osteoporosis screening: an Iowa Research Network
      (IRENE) study.
AB  - BACKGROUND: Primary care physicians often fail to diagnose low bone density. This
      pilot study assessed 2 interventions for their effect on bone mineral density
      testing. METHODS: Five practices in the Iowa Research Network were randomized: 2
      to chart reminder alone (CR), 2 to chart reminder plus mailed patient education
      (CR+PtEd), and one to usual care. A total of 204 women aged 65 years or older
      were recruited from within these practices. Bayesian hierarchical analyses were
      used instead of traditional statistical methods to take advantage of collateral
      data and to adjust for differences between clinics at baseline. RESULTS: After
      the intervention, the rates of completed bone mineral density testing were 45.2%
      in the CR+PtEd group, 31.4% in the chart remainder only group, and 9.7% in the
      usual care practice. Bayesian analysis adjusted for patient and clinic
      characteristics, which made use of collateral data, gave an odds ratio of 5.47
      for the effect of CR+PtEd group. The Bayesian P was .029 and the one-sided 95%
      credible interval for the odds ratio was greater than 1.2. The effect of CR+PtEd
      was confirmed by sensitivity analyses. Traditional hierarchical analysis adjusted
      for practice characteristics could not be used to estimate statistical
      significance because there were not enough clinics to accommodate a model that
      included all the important covariables. CONCLUSIONS: Specific chart reminders to
      physicians combined with mailed patient education substantially increased the
      levels of bone density testing and could potentially be used to improve
      osteoporosis screening in primary care. Bayesian hierarchical analysis makes it
      possible to assess practice-level interventions when few practices are
      randomized.

PMID- 19587250
TI  - Personal health behaviors are associated with physical and mental unhealthy days:
      a Prescription for Health (P4H) practice-based research networks study.
AB  - BACKGROUND: Because unhealthy behaviors have been shown to predict premature
      mortality and quality of life is linked to chronic disease, it is plausible that
      there is a relationship between unhealthy behaviors and a patient's overall well
      being. METHODS: Baseline data from the Robert Wood Johnson Foundation's
      Prescription for Health initiative were used. Using various methods, 9 practice
      based research networks collected common data about cigarette smoking, diet,
      exercise, and perceived physical and mental health from 5358 patients from 67
      practices. Multilevel ordinal regression modeling was used to examine the
      relationship between risk behaviors and physical or mental unhealthy days.
      RESULTS: Smoking, unhealthy diet, and inactivity were associated with more self
      reported unhealthy days after adjusting for clustering and significant
      covariates. Smoking was associated with increased odds of more unhealthy days
      (odds ratio [OR], 1.51; P < .0001), as was a poor diet (OR, 1.10; P < .0001).
      More exercise (OR, 0.96; P = .0005) was associated with decreased odds of
      physical or mental unhealthy days. CONCLUSION: Unhealthy patient behaviors were
      associated with increased odds of physical or mental unhealthy days, suggesting a
      further reason primary care clinicians should address behavior change with
      patients. Implementing a brief, 2-question, quality of life screening would
      target groups of primary care patients with a higher prevalence of unhealthy
      behaviors.

PMID- 19587251
TI  - Risk factors for methicillin-resistant Staphylococcal aureus skin and soft tissue
      infections presenting in primary care: a South Texas Ambulatory Research Network
      (STARNet) study.
AB  - PURPOSE: To examine skin and soft tissue infections presenting at 4 primary care
      clinics and assess if historical risk factors and examination findings were
      associated with a positive methicillin-resistant Staphylococcus aureus (MRSA)
      culture. METHODS: During the 10-month observational study (April 2007 through
      January 2008), physicians in 5 practices across South Texas collected history,
      physical examination findings, culture results, and antibiotic(s) prescribed for
      all patients presenting with a skin or soft tissue infection. Analyses were
      conducted to determine the relationship between historical indicators, location
      of lesions, and examination findings with a positive MRSA culture. RESULTS:
      Across 4 practices, 164 cases of skin and soft tissue infections were collected
      during 10 months. Of the 94 with a culture, 63 (67%) were MRSA positive. Patients
      working in or exposed to a health care setting were more likely to have a culture
      positive for MRSA, as were those presenting with an abscess. MRSA-positive
      lesions were also significantly smaller in size. CONCLUSIONS: Because of the high
      prevalence of MRSA skin and soft tissue infections among patients presenting to
      family physicians, presumptive treatment for MRSA may be indicated. However,
      increasing levels of resistance to current antibiotics is concerning and warrants
      development of alternative management strategies.

PMID- 19587252
TI  - Improving maternal care with a continuous quality improvement strategy: a report
      from the Interventions to Minimize Preterm and Low Birth Weight Infants through
      Continuous Improvement Techniques (IMPLICIT) Network.
AB  - BACKGROUND: Maternal medical care (prenatal and postpartum) involves a set of
      clinical interventions addressing risk factors associated with important maternal
      and infant outcomes. Programs to increase the rate of delivery of these
      interventions in clinical practice have not been widely implemented. METHODS: A
      practice-based research network focused on developing continuous quality
      improvement (CQI) processes for maternal care among 10 family medicine residency
      training sites in the northeastern United States (the IMPLICIT Network) from
      January 2003 through September 2007. Documented delivery of 5 standard maternal
      care interventions was assessed before and after initiating a program to increase
      their frequency. Proportion chart analyses were conducted comparing the period
      before and after implementation of the CQI interventions. RESULTS: Data were
      available for 3936 pregnancies during the course of the study period. Results
      varied across the clinical interventions. Significant improvement in care
      processes was seen for 3 screening activities: (1) prenatal depression
      symptomatology (by 15 weeks' gestation); (2) screening for smoking at 30 weeks'
      gestation; (3) and postpartum contraception planning. Screening for smoking by 15
      weeks' gestation and testing for asymptomatic bacteriuria were already conducted
      >90% of the time during the baseline period and did not increase significantly
      after initiating the CQI program. Screening for postpartum depression
      symptomatology was recorded in 50% to 60% of women before the CQI program and did
      not increase significantly. CONCLUSIONS: A practice-based research network of
      family medicine residency practices focused on CQI outcomes was successful in
      increasing the delivery of some maternal care interventions.

PMID- 19587254
TI  - Diving medicine: a review of current evidence.
AB  - Recreational scuba diving is a growing sport worldwide, with an estimated 4
      million sport divers in the United States alone. Because divers may seek medical
      care for a disorder acquired in a remote location, physicians everywhere should
      be familiar with the physiology, injury patterns, and treatment of injuries and
      illnesses unique to the underwater environment. Failure to properly recognize,
      diagnose, and appropriately treat some diving injuries can have catastrophic
      results. In addition, recreational dive certification organizations require
      physical examinations for medical clearance to dive. This article will review
      both common and potentially life-threatening conditions associated with diving
      and will review current evidence behind fitness to dive considerations for
      elderly divers and those with common medical conditions.

PMID- 19587255
TI  - One presentation, two continents: left wrist myositis of distinct etiology in
      genetically similar individuals.
AB  - A 34-year-old man presented with a 5-day history of rapid onset weakness of the
      left wrist flexor muscles, associated with fever, sore throat, arthralgias, and
      myalgias. A literature review to answer the question, "What could cause focal
      muscle weakness, fever, and myalgias?" yielded several case reports describing
      initial presentations of polymyositis or unusual presentations of various
      infectious agents. Interestingly, the man in our case had a cousin in France,
      with whom he had no recent contact, who presented with the same symptoms
      approximately 3 months earlier. Because of our patient's recent travel history,
      testing was performed for Lyme disease, confirming our diagnosis. The man's
      cousin, however, had been similarly tested and was found negative for Lyme
      disease.

PMID- 19587253
TI  - Virtual reality skills training for health care professionals in alcohol
      screening and brief intervention.
AB  - BACKGROUND: Educating physicians and other health care professionals about the
      identification and treatment of patients who drink more than recommended limits
      is an ongoing challenge. METHODS: An educational randomized controlled trial was
      conducted to test the ability of a stand-alone training simulation to improve the
      clinical skills of health care professionals in alcohol screening and
      intervention. The "virtual reality simulation" combined video, voice recognition,
      and nonbranching logic to create an interactive environment that allowed trainees
      to encounter complex social cues and realistic interpersonal exchanges. The
      simulation included 707 questions and statements and 1207 simulated patient
      responses. RESULTS: A sample of 102 health care professionals (10 physicians; 30
      physician assistants or nurse practitioners; 36 medical students; 26 pharmacy,
      physican assistant, or nurse practitioner students) were randomly assigned to a
      no training group (n = 51) or a computer-based virtual reality intervention (n =
      51). Professionals in both groups had similar pretest standardized patient
      alcohol screening skill scores: 53.2 (experimental) vs 54.4 (controls), 52.2 vs
      53.7 alcohol brief intervention skills, and 42.9 vs 43.5 alcohol referral skills.
      After repeated practice with the simulation there were significant increases in
      the scores of the experimental group at 6 months after randomization compared
      with the control group for the screening (67.7 vs 58.1; P < .001) and brief
      intervention (58.3 vs 51.6; P < .04) scenarios. CONCLUSIONS: The technology
      tested in this trial is the first virtual reality simulation to demonstrate an
      increase in the alcohol screening and brief intervention skills of health care
      professionals.

PMID- 19587257
TI  - Practice-based research is community engagement.

PMID- 19587256
TI  - Building a pan-Canadian primary care sentinel surveillance network: initial
      development and moving forward.
AB  - The development of a pan-Canadian network of primary care research networks for
      studying issues in primary care has been the vision of Canadian primary care
      researchers for many years. With the opportunity for funding from the Public
      Health Agency of Canada and the support of the College of Family Physicians of
      Canada, we have planned and developed a project to assess the feasibility of a
      network of networks of family medicine practices that exclusively use electronic
      medical records. The Canadian Primary Care Sentinel Surveillance Network will
      collect longitudinal data from practices across Canada to assess the primary care
      epidemiology and management of 5 chronic diseases: hypertension, diabetes,
      depression, chronic obstructive lung disease, and osteoarthritis. This article
      reports on the 7-month first phase of the feasibility project of 7 regional
      networks in Canada to develop a business plan, including governance, mission, and
      vision; develop memorandum of agreements with the regional networks and their
      respective universities; develop and obtain approval of research ethics board
      applications; develop methods for data extraction, a Canadian Primary Care
      Sentinel Surveillance Network database, and initial assessment of the types of
      data that can be extracted; and recruitment of 10 practices at each network that
      use electronic medical records. The project will continue in phase 2 of the
      feasibility testing until April 2010.

PMID- 19587258
TI  - The marriage of community-based participatory research and practice-based
      research networks: can it work? -A Research Involving Outpatient Settings Network
      (RIOS Net) study.
AB  - BACKGROUND: Interest in community-based participatory research (CBPR) has surged
      during the last several years because of its potential to enhance the quality and
      usefulness of research outcomes. Practice-based research networks (PBRNs)
      potentially can provide a bridge between the research endeavor and communities;
      PBRNs have been identified as a promising venue for CBPR. However, this marriage
      of CBPR and PBRNs faces many challenges, such as locus of project idea
      generation, time constraints, and funding limitations. METHODS: This was a case
      study of the application of the CBPR model and CBPR principles specific to PBRN
      research using a recent PBRN study of communication about traditional,
      complementary, and alternative medicines. RESULTS: Challenges (eg, added cost,
      time) and benefits (eg, improved research data collection process, enhanced data
      analysis) resulted from application of the CBPR model and are detailed.
      CONCLUSIONS: For practical and ethical reasons, PBRNs need to adopt the CBPR
      approach for certain types, if not all, of their research. This might require
      operational adaptations by the PBRN (eg, a community advisory board, community
      membership in the network board of directors, and outreach to community groups
      for input into network priorities) as well as dedicated time and funding.

PMID- 19587259
TI  - Barriers, enablers, and incentives for research participation: a report from the
      Ambulatory Care Research Network (ACRN).
AB  - BACKGROUND: Supported by a supplement to our Clinical and Translational Science
      Award, we studied the feasibility of implementing clinical research in Northern
      Manhattan community practices that primarily serve Hispanic patients. METHODS: We
      applied a mixed-methods approach (surveys, focus groups, interviews) based on the
      PRECEDE-PROCEED model to determine the level of interest in clinical research
      among community clinicians (both practice-based research network [PBRN] members
      and non-PBRN members), the perceived barriers that hamper participation in
      clinical research, and the perceived facilitators for conducting research in such
      practices. RESULTS: Survey and qualitative data indicated strong interest in
      clinical research among current and potential PBRN members if it was relevant to
      improving quality of care in their practice or community. They also identified
      important perceived barriers (lack of time, inadequate training in research
      methods, lack of collaborators and support staff, institutional review board
      hurdles, and community distrust of research) and the necessary requirements for
      overcoming barriers to conducting research in busy clinical settings, which
      included collaborators, mentors, research support staff, and a trusting patient
      clinician relationship. CONCLUSION: It is feasible to conduct clinical research
      studies in urban community medical practices if the topics are relevant to the
      community and appropriate enabling structures and processes are put into place.

PMID- 19587260
TI  - Internet-based training in a practice-based research network consortium: a report
      from the Primary Care Multiethnic Network (PRIME Net).
AB  - BACKGROUND: Continuing growth of the research spectrum of practice-based research
      networks (PBRNs) creates a need (1) for new approaches to training clinicians in
      research protocols and (2) to standardize clinician data collection. Each
      existing training method has shortcomings when used in geographically dispersed
      PBRNs. We describe here the use and costs of Internet-based training in support
      of a research protocol across a PBRN consortium. METHODS: Clinicians in 4 PBRNs
      in the PRIME Net consortium participated in training for a study of acanthosis
      nigricans (AN). We compared results of pre- and posttraining assessments of
      knowledge and ability to correctly diagnosis AN. We also calculated costs for
      placement of the training on the Internet. RESULTS: Among 103 participating
      clinicians, statistically significant increases in knowledge acquisition were
      demonstrated for all but 2 of the individual topics and in total scores on the
      assessments. AN diagnostic sensitivity increased from 52% to 99% to 96% to 100%,
      whereas specificity increased from 70% to 96% to 74% to 97%. Total costs for the
      web aspects of the training were $3732. CONCLUSION: The Internet can be an
      effective and feasible alternative method for training clinicians in support of
      PBRN research.

PMID- 19587261
TI  - Practice-based research network studies and institutional review boards: two new
      issues.
AB  - BACKGROUND: Practice-based research network (PBRN) study investigators must
      interface with multiple Institutional Review Boards (IRBs), many of which are
      unfamiliar with PBRN research. OBJECTIVE: To present 2 IRB-related issues that
      have not appeared in the literature but occurred during the course of a large 5
      year PBRN study involving 32 sites dispersed around the United States. RESULTS:
      Our study required IRB approval from a total of 19 local, hospital, academic
      center, and professional organization-based IRBs that reviewed a protocol of
      postpartum depression screening and follow-up completed in English or Spanish.
      Initial approval of the protocol and consent forms proceeded with only the usual
      barriers of submitting 19 different forms, and no protocol amendments were
      required. However, 2 unanticipated IRB issues provided significant additional
      work for the study team and the local practice sites. First, several IRBs
      required staff to repeat human subjects training every 1 to 2 years, resulting in
      92 practicing physicians, residents, and members of the nursing staff spending
      time completing the exact same human subjects' training at least twice during the
      course of this study. Second, 17 of the 19 IRBs required that the patient be
      given consent forms that were newly stamped and dated each year, requiring the
      central site to reprint and replace consent forms yearly. Because not all IRBs
      returned the newly stamped and dated forms in a timely fashion, study enrollment
      with valid consent forms was interrupted in 4 sites for periods of 2 to 13 weeks.
      CONCLUSIONS: IRB requirements not directly responsive to federal regulations can
      add significant costs, frustrations, and burdens to PBRN studies. Non-federally
      mandated IRB requirements should be based on an identified need with evidence to
      support the solution.

PMID- 19587262
TI  - Comparison of point of care and laboratory HbA1c analysis: a MetroNet study.
AB  - BACKGROUND: Evaluating new technology in clinical practice is an important
      component of translating research into practice. We considered the feasibility of
      using a Clinical Laboratory Improvement Amendments (CLIA)-waived point of care
      (POC) glycohemoglobin (HbA1c) methodology in busy family medicine centers by
      comparing the results of POC HbA1c and laboratory analysis results. METHODS:
      Recruited from 5 MetroNet practices, the participants were adult diabetic
      patients having blood samples drawn for laboratory analysis of HbA1c. Each agreed
      to provide a capillary blood sample for POC testing. RESULTS: With data on 99
      paired samples, the POC method yielded a mean HbA1c of 7.38%, which was
      equivalent to the mean of 7.53% produced with all combined standard laboratory
      analyses. The Pearson correlation between POC and the laboratory analysis test
      results was 0.884 (P < .001). POC test sensitivity was 81.8% and specificity was
      93.2%. Eighteen percent of patients with an HbA1c > = 7% by laboratory analysis
      were not identified as such by the POC test. CONCLUSIONS: Before adopting a POC
      methodology, practices are encouraged to review its feasibility in the context of
      the office routine, and also to conduct periodic comparisons of the accuracy of
      POC test results compared with those from laboratory analysis.

PMID- 19587263
TI  - Leptin receptor is expressed in thymus medulla and leptin protects against thymic
      remodeling during endotoxemia-induced thymus involution.
AB  - Leptin deficiency in mice results in chronic thymic atrophy, suppressed cell
      mediated immunity, and decreased numbers of total lymphocytes, suggesting a key
      role for the metabolic hormone leptin in regulating thymopoiesis and overall
      immune homeostasis. Unfortunately, the thymus is highly susceptible to stress
      induced acute involution. Prolonged thymus atrophy in stress situations can
      contribute to peripheral T cell deficiency or inhibit immune reconstitution.
      Little is known, however, about specific roles for leptin signaling in the thymus
      or the underlying mechanisms driving thymic involution or thymic recovery after
      acute stress. We report here that leptin receptor expression is restricted in
      thymus to medullary epithelial cells. Using a model of endotoxemia-induced acute
      thymic involution and recovery, we have demonstrated a role for supraphysiologic
      leptin in protection of thymic epithelial cells (TECs). We also present data in
      support of our hypothesis that leptin treatment decreases in vivo endotoxemia
      induced apoptosis of double positive thymocytes and promotes proliferation of
      double negative thymocytes through a leptin receptor isoform b-specific
      mechanism. Furthermore, our studies have revealed that leptin treatment increases
      thymic expression of interleukin-7, an important soluble thymocyte growth factor
      produced by medullary TECs. Taken together, these studies support an intrathymic
      role for the metabolic hormone leptin in maintaining healthy thymic epithelium
      and promoting thymopoiesis, which is revealed when thymus homeostasis is
      perturbed by endotoxemia.

PMID- 19587265
TI  - Systemic administration of oxytocin reduces basal and lipopolysaccharide-induced
      ghrelin levels in healthy men.
AB  - Oxytocin (OXT) and ghrelin have several common properties such as the involvement
      in the first phase response to stressors, in appetite regulation, and in the
      modulation of neural functions. Despite a recent study showing that
      intraventricular administration of ghrelin activates OXT neurons, little is known
      on the cross-talk between these two peptides. Here, we investigated the role of
      the i.v. administration of OXT on circulating ghrelin concentrations under
      fasting conditions and during the lipopolysaccharide (LPS)-induced endotoxemia. A
      randomized placebo-controlled cross-over study was performed in ten healthy men.
      In four study sessions, the participants received once placebo, once OXT (1
      pmol/kg per min over 90 min), once LPS (2 ng/kg), and once both OXT and LPS.
      Plasma ghrelin, glucose, and free fatty acid (FFA) levels were measured at
      regular intervals during the first 6 h following the LPS bolus. Systemic
      administration of OXT decreased within 1 h plasma ghrelin levels (611+/-54 vs
      697+/-52 pg/ml in placebo days, P=0.013) and increased plasma glucose and FFA
      concentrations (P=0.002 and P=0.005 respectively). OXT also reduced the LPS
      induced surge in ghrelin at time point 2 h (P=0.021). In summary, i.v.
      administration of OXT decreases circulating levels of ghrelin during fasting, as
      well as following LPS-induced endotoxemia in healthy men. The cross-talk between
      OXT and ghrelin might be important in the regulation of energy homeostasis and
      stress responses.

PMID- 19587264
TI  - Degradation of IRS1 leads to impaired glucose uptake in adipose tissue of the
      type 2 diabetes mouse model TALLYHO/Jng.
AB  - The TALLYHO/Jng (TH) mouse strain is a polygenic model for type 2 diabetes (T2D)
      characterized by moderate obesity, impaired glucose tolerance and uptake, insulin
      resistance, and hyperinsulinemia. The goal of this study was to elucidate the
      molecular mechanisms responsible for the reduced glucose uptake and insulin
      resistance in the adipose tissue of this model. The translocation and
      localization of glucose transporter 4 (GLUT4) to the adipocyte plasma membrane
      were impaired in TH mice compared to control C57BL6/J (B6) mice. These defects
      were associated with decreased GLUT4 protein, reduced phosphatidylinositol 3
      kinase activity, and alterations in the phosphorylation status of insulin
      receptor substrate 1 (IRS1). Activation of c-Jun N-terminal kinase 1/2, which can
      phosphorylate IRS1 on Ser307, was significantly higher in TH mice compared with
      B6 controls. IRS1 protein but not mRNA levels was found to be lower in TH mice
      than controls. Immunoprecipitation with anti-ubiquitin and western blot analysis
      of IRS1 protein revealed increased total IRS1 ubiquitination in adipose tissue of
      TH mice. Suppressor of cytokine signaling 1, known to promote IRS1 ubiquitination
      and subsequent degradation, was found at significantly higher levels in TH mice
      compared with B6. Immunohistochemistry showed that IRS1 colocalized with the 20S
      proteasome in proteasomal structures in TH adipocytes, supporting the notion that
      IRS1 is actively degraded. Our findings suggest that increased IRS1 degradation
      and subsequent impaired GLUT4 mobilization play a role in the reduced glucose
      uptake in insulin resistant TH mice. Since low-IRS1 levels are often observed in
      human T2D, the TH mouse is an attractive model to investigate mechanisms of
      insulin resistance and explore new treatments.

PMID- 19587266
TI  - Genetic background influences embryonic lethality and the occurrence of neural
      tube defects in Men1 null mice: relevance to genetic modifiers.
AB  - Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) gene cause
      parathyroid, pancreatic and pituitary tumours in man. MEN1 mutations also cause
      familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations,
      in different families, can cause either FIHP or MEN1. This suggests a role for
      genetic background and modifier genes in altering the expression of a mutation.
      We investigated the effects of genetic background on the phenotype of embryonic
      lethality that occurs in a mouse model for MEN1. Men1(+/-) mice were backcrossed
      to generate C57BL/6 and 129S6/SvEv incipient congenic strains, and used to obtain
      homozygous Men1(-/-) mice. No viable Men1(-/-) mice were obtained. The analysis
      of 411 live embryos obtained at 9.5-16.5 days post-coitum (dpc) revealed that
      significant deviations from the expected Mendelian 1:2:1 genotype ratio were
      first observed at 12.5 and 14.5 dpc in the 129S6/SvEv and C57BL/6 strains
      respectively (P<0.05). Moreover, live Men1(-/-) embryos were absent by 13.5 and
      15.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively thereby indicating an
      earlier lethality by 2 days in the 129S6/SvEv strain (P<0.01). Men1(-/-) embryos
      had macroscopic haemorrhages, and histology and optical projection tomography
      revealed them to have internal haemorrhages, myocardial hypotrophy, pericardial
      effusion, hepatic abnormalities and neural tube defects. The neural tube defects
      occurred exclusively in 129S6/SvEv embryos (21 vs 0%, P<0.01). Thus, our findings
      demonstrate the importance of genetic background in influencing the phenotypes of
      embryonic lethality and neural tube defects in Men1(-/-) mice, and implicate a
      role for genetic modifiers.

PMID- 19587267
TI  - Faithful expression of multiple proteins via 2A-peptide self-processing: a
      versatile and reliable method for manipulating brain circuits.

PMID- 19587268
TI  - The temporoparietal junction as a part of the "when" pathway.

PMID- 19587269
TI  - Differential modulation of long-term depression by acute stress in the rat dorsal
      and ventral hippocampus.
AB  - The ventral hippocampus (VH) was recently shown to express lower-magnitude long
      term potentiation (LTP) than the dorsal hippocampus (DH). An exposure to acute
      stress reversed this difference, and VH slices from stressed rats expressed
      larger LTP than controls, whereas LTP in the DH was suppressed by stress. We have
      now used long-term depression (LTD)-generating trains of stimulation to examine
      whether this differential LTP reflects a genuine difference in synaptic
      modifiability between the two sectors of the hippocampus. Surprisingly, slices of
      DH and VH express similar magnitudes of LTD. However, while prior stress enhanced
      LTD in the DH, it actually converted LTD to slow-onset, robust LTP in the VH.
      These two effects of stress on LTD were blocked by glucocorticosterone receptor
      (GR) and mineralocorticosterone receptor (MR) antagonists, respectively. Acute
      exposure of slices to a GR agonist dexamethasone facilitated LTD in slices of
      both DH and VH, while activation of MRs by aldosterone converted LTD to LTP in
      both regions. Thus, differential activation of the two species of corticosterone
      receptors determines the ability of the two sectors of the hippocampus to undergo
      plastic changes in response to LTD-inducing stimulation.

PMID- 19587270
TI  - Alpha-latrotoxin stimulates a novel pathway of Ca2+-dependent synaptic exocytosis
      independent of the classical synaptic fusion machinery.
AB  - Alpha-latrotoxin induces neurotransmitter release by stimulating synaptic vesicle
      exocytosis via two mechanisms: (1) A Ca(2+)-dependent mechanism with neurexins as
      receptors, in which alpha-latrotoxin acts like a Ca(2+) ionophore, and (2) a
      Ca(2+)-independent mechanism with CIRL/latrophilins as receptors, in which alpha
      latrotoxin directly stimulates the transmitter release machinery. Here, we show
      that the Ca(2+)-independent release mechanism by alpha-latrotoxin requires the
      synaptic SNARE-proteins synaptobrevin/VAMP and SNAP-25, and, at least partly, the
      synaptic active-zone protein Munc13-1. In contrast, the Ca(2+)-dependent release
      mechanism induced by alpha-latrotoxin does not require any of these components of
      the classical synaptic release machinery. Nevertheless, this type of exocytotic
      neurotransmitter release appears to fully operate at synapses, and to stimulate
      exocytosis of the same synaptic vesicles that participate in physiological action
      potential-triggered release. Thus, synapses contain two parallel and independent
      pathways of Ca(2+)-triggered exocytosis, a classical, physiological pathway that
      operates at the active zone, and a novel reserve pathway that is recruited only
      when Ca(2+) floods the synaptic terminal.

PMID- 19587271
TI  - Reassessment of corticospinal tract regeneration in Nogo-deficient mice.
AB  - The myelin-derived neurite growth inhibitor Nogo has been proposed to play a
      major role in blocking axon regeneration in the CNS after injuries. However, past
      studies have produced mixed results regarding the regenerative phenotype of
      various Nogo-deficient mouse lines after experimental spinal cord injury. Two
      lines did not display enhanced corticospinal tract (CST) regeneration, and one
      displayed modest regeneration. A fourth line, a Nogo-A,B gene-trap mutant, was
      instead reported to exhibit extensive CST regeneration, but the results were
      later found to be inadvertently confounded with an axon labeling artifact. Of the
      four Nogo mutant lines studied so far, three continue to express some isoform(s)
      of Nogo, leaving open the question whether any remaining Nogo protein contributes
      to the modest regenerative phenotype reported in some. The remaining Nogo mutant
      line studied was confounded by the unexplained rescue of embryonic lethality
      associated with this mutation. To gain a better understanding of the contribution
      of Nogo as an inhibitor of regeneration of CNS axons, and particularly CST axons,
      we reanalyzed the Nogo-A,B gene-trap mutant line and analyzed a novel, fully
      viable Nogo deletion mutant line that is null for all known isoforms of Nogo. Our
      analyses failed to reveal any enhanced CST regeneration after experimental spinal
      cord injury in either line. These results indicate that Nogo alone does not
      account for lack of CST regeneration and have implications for current
      therapeutic development for spinal cord injury in humans by targeting Nogo.

PMID- 19587273
TI  - Therapeutic administration of plasminogen activator inhibitor-1 prevents hypoxic
      ischemic brain injury in newborns.
AB  - Disruption of the integrity of the blood-brain barrier (BBB) is an important
      mechanism of cerebrovascular diseases, including neonatal cerebral hypoxia
      ischemia (HI). Although both tissue-type plasminogen activator (tPA) and matrix
      metalloproteinase-9 (MMP-9) can produce BBB damage, their relationship in
      neonatal cerebral HI is unclear. Here we use a rodent model to test whether the
      plasminogen activator (PA) system is critical for MMP-9 activation and HI-induced
      brain injury in newborns. To test this hypothesis, we examined the therapeutic
      effect of intracerebroventricular injection of plasminogen activator inhibitor-1
      (PAI-1) in rat pups subjected to unilateral carotid artery occlusion and systemic
      hypoxia. We found that the injection of PAI-1 greatly reduced the activity of
      both tPA and urokinase-type plasminogen activator after HI. It also blocked HI
      induced MMP-9 activation and BBB permeability at 24 h of recovery. Furthermore,
      magnetic resonance imaging and histological analysis showed the PAI-1 treatment
      reduced brain edema, axonal degeneration, and cortical cell death at 24-48 h of
      recovery. Finally, the PAI-1 therapy provided a dose-dependent decrease of brain
      tissue loss at 7 d of recovery, with the therapeutic window at 4 h after the HI
      insult. Together, these results suggest that the brain PA system plays a pivotal
      role in neonatal cerebral HI and may be a promising therapeutic target in infants
      suffering hypoxic-ischemic encephalopathy.

PMID- 19587272
TI  - Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional
      implications for alcoholism.
AB  - The glutamate receptor-associated protein Homer2 regulates alcohol-induced
      neuroplasticity within the nucleus accumbens (NAC), but the precise intracellular
      signaling cascades involved are not known. This study examined the role for NAC
      metabotropic glutamate receptor (mGluR)-Homer2-phosphatidylinositol 3-kinase
      (PI3K) signaling in regulating excessive alcohol consumption within the context
      of the scheduled high alcohol consumption (SHAC) model of binge alcohol drinking.
      Repeated bouts of binge drinking ( approximately 1.5 g/kg per 30 min) elevated
      NAC Homer2a/b expression and increased PI3K activity in this region. Virus
      mediated knockdown of NAC Homer2b expression attenuated alcohol intake, as did an
      intra-NAC infusion of the mGluR5 antagonist MPEP [2-methyl-6
      (phenylethynyl)pyridine hydrochloride] (0.1-1 microg/side) and the PI3K
      antagonist wortmannin (50 ng/side), supporting necessary roles for
      mGluR5/Homer2/PI3K in binge alcohol drinking. Moreover, when compared with wild
      type littermates, transgenic mice with an F1128R point mutation in mGluR5 that
      markedly reduces Homer binding exhibited a 50% reduction in binge alcohol
      drinking, which was related to reduced NAC basal PI3K activity. Consistent with
      the hypothesis that mGluR5-Homer-PI3K signaling may be a mechanism governing
      excessive alcohol intake, the "anti-binge" effects of MPEP and wortmannin were
      not additive, nor were they observed in the mGluR5(F1128R) transgenic mice.
      Finally, mice genetically selected for a high versus low SHAC phenotype differed
      in NAC mGluR, Homer2, and PI3K activity, consistent with the hypothesis that
      augmented NAC mGluR5-Homer2-PI3K signaling predisposes a high binge alcohol
      drinking phenotype. Together, these data point to an important role for NAC
      mGluR5-Homer2-PI3K signaling in regulating binge-like alcohol consumption that
      has relevance for our understanding of the neurobiology of alcoholism and its
      pharmacotherapy.

PMID- 19587274
TI  - Domain general mechanisms of perceptual decision making in human cortex.
AB  - To successfully interact with objects in the environment, sensory evidence must
      be continuously acquired, interpreted, and used to guide appropriate motor
      responses. For example, when driving, a red light should motivate a motor command
      to depress the brake pedal. Single-unit recording studies have established that
      simple sensorimotor transformations are mediated by the same neurons that
      ultimately guide the behavioral response. However, it is also possible that these
      sensorimotor regions are the recipients of a modality-independent decision signal
      that is computed elsewhere. Here, we used functional magnetic resonance imaging
      and human observers to show that the time course of activation in a subregion of
      the right insula is consistent with a role in accumulating sensory evidence
      independently from the required motor response modality (saccade vs manual).
      Furthermore, a combination of computational modeling and simulations of the blood
      oxygenation level-dependent response suggests that this region is not simply
      recruited by general arousal or by the tonic maintenance of attention during the
      decision process. Our data thus raise the possibility that a modality-independent
      representation of sensory evidence may guide activity in effector-specific
      cortical areas before the initiation of a behavioral response.

PMID- 19587275
TI  - Positive AMPA receptor modulation rapidly stimulates BDNF release and increases
      dendritic mRNA translation.
AB  - Brain-derived neurotrophic factor (BDNF) stimulates local dendritic mRNA
      translation and is involved in formation and consolidation of memory. 2H,3H,6aH
      pyrrolidino[2'',1''-3',2']1,3-oxazino[6',5'-5,4]-benzo[e]1,4-dioxan-10-one
      (CX614), one of the best-studied positive AMPA receptor modulators (also known as
      ampakines), increases BDNF mRNA and protein and facilitates long-term
      potentiation (LTP) induction. Several other ampakines also improve performance in
      various behavioral and learning tasks. Since local dendritic protein synthesis
      has been implicated in LTP stabilization and in memory consolidation, this study
      investigated whether CX614 could influence synaptic plasticity by upregulating
      dendritic protein translation. CX614 treatment of primary neuronal cultures and
      acute hippocampal slices rapidly activated the translation machinery and
      increased local dendritic protein synthesis. CX614-induced activation of
      translation was blocked by K252a [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10
      hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4
      i][1,6]benzodiazocine-10-carboxylic acid methyl ester], CNQX, APV, and TTX, and
      was inhibited in the presence of an extracellular BDNF scavenger, TrkB-Fc. The
      acute effect of CX614 on translation was mediated by increased BDNF release as
      demonstrated with a BDNF scavenging assay using TrkB-Fc during CX614 treatment of
      cultured primary neurons and was blocked by nifedipine, ryanodine, and lack of
      extracellular Ca(2+) in acute hippocampal slices. Finally, CX614, like BDNF,
      rapidly increased dendritic translation of an exogenous translation reporter.
      Together, our results demonstrate that positive modulation of AMPA receptors
      rapidly stimulates dendritic translation, an effect mediated by BDNF secretion
      and TrkB receptor activation. They also suggest that increased BDNF secretion and
      stimulation of local protein synthesis contribute to the effects of ampakines on
      synaptic plasticity.

PMID- 19587276
TI  - Individual differences in true and false memory retrieval are related to white
      matter brain microstructure.
AB  - We sometimes vividly remember things that did not happen, a phenomenon with
      general relevance, not only in the courtroom. It is unclear to what extent
      individual differences in false memories are driven by anatomical differences in
      memory-relevant brain regions. Here we show in humans that microstructural
      properties of different white matter tracts as quantified using diffusion tensor
      imaging are strongly correlated with true and false memory retrieval. To
      investigate these hypotheses, we tested a large group of participants in a
      version of the Deese-Roediger-McDermott paradigm (recall and recognition) and
      subsequently obtained diffusion tensor images. A voxel-based whole-brain level
      linear regression analysis was performed to relate fractional anisotropy to
      indices of true and false memory recall and recognition. True memory was
      correlated to diffusion anisotropy in the inferior longitudinal fascicle, the
      major connective pathway of the medial temporal lobe, whereas a greater proneness
      to retrieve false items was related to the superior longitudinal fascicle
      connecting frontoparietal structures. Our results show that individual
      differences in white matter microstructure underlie true and false memory
      performance.

PMID- 19587278
TI  - How ongoing fluctuations in human visual cortex predict perceptual awareness:
      baseline shift versus decision bias.
AB  - Visual perception fluctuates across repeated presentations of the same near
      threshold stimulus. These perceptual fluctuations have often been attributed to
      baseline shifts--i.e., ongoing modulations of neuronal activity in visual areas-
      driven by top-down attention. Using magnetoencephalography, we directly tested
      whether ongoing attentional modulations could fully account for the perceptual
      impact of prestimulus activity on a subsequent seen-unseen decision. We found
      that prestimulus gamma-band fluctuations in lateral occipital areas (LO)
      predicted visual awareness, but did not reflect the focus of spatial attention.
      Moreover, these prestimulus signals influenced the decision outcome independently
      from the strength of the following visual response, suggesting that baseline
      shifts alone could not explain their perceptual impact. Using a straightforward
      decision-making model based on the accumulation of sensory evidence over time, we
      show that prestimulus gamma-band fluctuations in LO behave as a decision bias at
      stimulus onset, irrespectively of subsequent stimulus processing. In contrast,
      spatial attention suppressed prestimulus alpha-band signals in the same region,
      and produced a sustained baseline shift that also predicted the outcome of the
      seen-unseen decision. Together, our results indicate that prestimulus
      fluctuations in visual areas can influence the conscious detection of an upcoming
      stimulus via two distinct mechanisms: an attention-driven baseline shift in the
      alpha range, and a decision bias in the gamma range.

PMID- 19587277
TI  - VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural
      progenitors in the rostral migratory stream in vivo.
AB  - The generation of new neurons in the olfactory bulb (OB) persists into adulthood
      and is a multistep process that includes proliferation, fate choice, migration,
      survival, and differentiation. Neural precursor cells destined to form olfactory
      interneurons arise in the subventricular zone (SVZ) and migrate along the rostral
      migratory stream (RMS) to the OB. Recently, some factors classically known from
      their effects on the vascular system have been found to influence different steps
      of adult neurogenesis. In the present study, we report a modulatory function for
      the vascular endothelial growth factor receptor-1 (VEGFR-1) in adult olfactory
      neurogenesis. We identified expression of VEGFR-1 in GFAP-positive cells within
      regions involved in neurogenesis of the adult mouse brain. To determine functions
      for VEGFR-1 in adult neurogenesis, we compared neural progenitor cell
      proliferation, migration, and differentiation from wild-type and VEGFR-1
      signaling-deficient mice (Flt-1TK(-/-) mice). Our data show that VEGFR-1
      signaling is involved in the regulation of proliferation of neuronal progenitor
      cells within the SVZ, migration along the RMS, and in neuronal differentiation
      and anatomical composition of interneuron subtypes within the OB. RMS migration
      in Flt-1TK(-/-) mice was altered mainly as a result of increased levels of its
      ligand VEGF-A, which results in an increased phosphorylation of VEGFR-2 in
      neuronal progenitor cells within the SVZ and the RMS. This study reveals that
      proper RMS migration is dependent on endogenous VEGF-A protein.

PMID- 19587279
TI  - Human variation in overriding attentional capture.
AB  - Attention can be directed either voluntarily based on the goals of the individual
      or involuntarily "captured" by salient stimuli in the immediate environment.
      Although involuntary capture is a critical means of directing attention, the
      completion of many common tasks requires our ability to ignore salient, but
      otherwise irrelevant stimuli while restricting our attention to stimuli that are
      related to our goals. Here, we report neurophysiological measures of spatial
      attention in humans that gauge an individual's ability to resist attentional
      capture from salient but irrelevant information. By measuring the rapid
      reallocation of spatial attention immediately after the onset of distractors, we
      observe that the ability to override attentional capture varies substantially
      across individuals and is strongly predicted by the specific working memory
      capacity of each person. High-capacity individuals were much more capable of
      resisting attentional capture than low-capacity individuals, who involuntarily
      reallocated spatial attention when distractors were present in the display. These
      results provide evidence that the poor attentional abilities associated with low
      memory capacity may stem from an inability to override attentional capture in the
      initial moments after the onset of distracting information.

PMID- 19587280
TI  - The positive allosteric modulator morantel binds at noncanonical subunit
      interfaces of neuronal nicotinic acetylcholine receptors.
AB  - We are interested in the positive allosteric modulation of neuronal nicotinic
      acetylcholine (ACh) receptors and have recently shown that the anthelmintic
      compound morantel potentiates by enhancing channel gating of the alpha3beta2
      subtype. Based on the demonstration that morantel-elicited currents were
      inhibited by the classic ACh competitor dihydro-beta-erythroidine in a
      noncompetitive manner and that morantel still potentiates at saturating
      concentrations of agonist (Wu et al., 2008), we hypothesized that morantel binds
      at the noncanonical beta2(+)/alpha3(-) subunit interface. In the present study,
      we created seven cysteine-substituted subunits by site-directed mutagenesis,
      choosing residues in the putative morantel binding site with the aid of
      structural homology models. We coexpressed the mutant subunits and their
      respective wild-type partners in Xenopus oocytes and characterized the morantel
      potentiation of ACh-evoked currents, as well as morantel-evoked currents, before
      and after treatment with a variety of methanethiosulfonate (MTS)-based compounds,
      using voltage-clamp recordings. The properties of four of the seven mutants, two
      residues on each side of the interface, were changed by MTS treatments.
      Coapplication with ACh enhanced the extent of MTS modification for
      alpha3A106Cbeta2 and alpha3beta2S192C receptors. The activities of two mutants,
      alpha3T115Cbeta2 and alpha3beta2T150C, were dramatically altered by MTS
      modification. For alpha3beta2T150C, while peak current amplitudes were reduced,
      potentiation was enhanced. For alpha3T115Cbeta2, both current amplitudes and
      potentiation were reduced. MTS modification and morantel were mutually
      inhibitory: MTS treatment decreased morantel-evoked currents and morantel
      decreased the rate of MTS modification. We conclude that the four residues
      showing MTS effects contribute to the morantel binding site.

PMID- 19587281
TI  - Phosphorylation of prion protein at serine 43 induces prion protein
      conformational change.
AB  - The cause of the conformational change of normal cellular prion protein (PrP)
      into its disease-associated form is unknown. Posttranslational modifications,
      such as glycosylation, acetylation, S-nitrosylation, and phosphorylation, are
      known to induce protein conformational changes. Here, we investigated whether
      phosphorylation could induce the conformational change of PrP because PrP
      contains several kinase motifs and has been found recently in the cytosol, in
      which kinases generally reside. Neuronal cyclin-dependent kinase 5 (Cdk5)
      phosphorylated recombinant PrP(23-231) at serine 43 (S43) in an in vitro kinase
      assay. Cdk5-phosphorylated PrP became proteinase K resistant, formed Congo Red
      positive fibrils, and formed aggregates that were immunostained with anti-PrP and
      anti-phospho-PrP(S43) (anti-pPrP(S43)). pPrP(S43) was detected in PrP/Cdk5/p25
      cotransfected N2a cells. Roscovitine inhibition of Cdk5 activity or transfection
      of N2a cells with mutant PrP S43A eliminated the anti-pPrP(S43)-immunopositive
      protein. Alkaline phosphatase-sensitive and proteinase K-resistant pPrP(S43)
      immunoreactivity was observed in scrapie-infected but not control-injected mice
      brains. These results raise the possibility that phosphorylation could represent
      a physiological mechanism of PrP conversion in vivo.

PMID- 19587283
TI  - Metaplastic regulation of long-term potentiation/long-term depression threshold
      by activity-dependent changes of NR2A/NR2B ratio.
AB  - In vivo experience induces changes in synaptic NMDA receptor (NMDAR) subunit
      components, which are correlated with subsequent modifications of synaptic
      plasticity. However, little is known about how these subunit changes regulate the
      induction threshold of subsequent plasticity. At hippocampal Schaffer collateral
      CA1 synapses, we first examined whether a recent history of neuronal activity
      could affect subsequent synaptic plasticity through its actions on NMDAR subunit
      components. We found that prior activity history produced by priming stimulations
      (PSs) across a wide range of frequencies (1-100 Hz) could induce bidirectional
      changes in the NR2A/NR2B ratio, which governs the threshold for subsequent long
      term potentiation/long-term depression (LTP/LTD). Manipulating the NR2A/NR2B
      ratio through partial NR2 subunit blockade mimicked the PS regulation of the
      LTP/LTD threshold. Our results demonstrate that activity-dependent changes in the
      NR2A/NR2B ratio can be critical factors in metaplastic regulation of the LTP/LTD
      threshold.

PMID- 19587282
TI  - A triplet repeat expansion genetic mouse model of infantile spasms syndrome,
      Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and
      adult cognitive and behavioral impairment.
AB  - Infantile spasms syndrome (ISS) is a catastrophic pediatric epilepsy with motor
      spasms, persistent seizures, mental retardation, and in some cases, autism. One
      of its monogenic causes is an insertion mutation [c.304ins (GCG)(7)] on the X
      chromosome, expanding the first polyalanine tract of the interneuron-specific
      transcription factor Aristaless-related homeobox (ARX) from 16 to 23 alanine
      codons. Null mutation of the Arx gene impairs GABA and cholinergic interneuronal
      migration but results in a neonatal lethal phenotype. We developed the first
      viable genetic mouse model of ISS that spontaneously recapitulates salient
      phenotypic features of the human triplet repeat expansion mutation.
      Arx((GCG)10+7) ("Arx plus 7") pups display abnormal spasm-like myoclonus and
      other key EEG features, including multifocal spikes, electrodecremental episodes,
      and spontaneous seizures persisting into maturity. The neurobehavioral profile of
      Arx mutants was remarkable for lowered anxiety, impaired associative learning,
      and abnormal social interaction. Laminar decreases of Arx+ cortical interneurons
      and a selective reduction of calbindin-, but not parvalbumin- or calretinin
      expressing interneurons in neocortical layers and hippocampus indicate that
      specific classes of synaptic inhibition are missing from the adult forebrain,
      providing a basis for the seizures and cognitive disorder. A significant
      reduction of calbindin-, NPY (neuropeptide Y)-expressing, and cholinergic
      interneurons in the mutant striatum suggest that dysinhibition within this
      network may contribute to the dyskinetic motor spasms. This mouse model narrows
      the range of critical pathogenic elements within brain inhibitory networks
      essential to recreate this complex neurodevelopmental syndrome.

PMID- 19587285
TI  - Maximal voluntary fingertip force production is not limited by movement speed in
      combined motion and force tasks.
AB  - Numerous studies of limbs and fingers propose that force-velocity properties of
      muscle limit maximal voluntary force production during anisometric tasks, i.e.,
      when muscles are shortening or lengthening. Although this proposition appears
      logical, our study on the simultaneous production of fingertip motion and force
      disagrees with this commonly held notion. We asked eight consenting adults to use
      their dominant index fingertip to maximize voluntary downward force against a
      horizontal surface at specific postures (static trials), and also during an
      anisometric "scratching" task of rhythmically moving the fingertip along a 5.8 +/
      0.5 cm target line. The metronome-timed flexion-extension movement speed varied
      36-fold from "slow" (1.0 +/- 0.5 cm/s) to "fast" (35.9 +/- 7.8 cm/s). As
      expected, maximal downward voluntary force diminished (44.8 +/- 15.6%; p = 0.001)
      when any motion (slow or fast) was added to the task. Surprisingly, however, a 36
      fold increase in speed did not affect this reduction in force magnitude. These
      remarkable results for such an ordinary task challenge the dominant role often
      attributed to force-velocity properties of muscle and provide insight into
      neuromechanical interactions. We propose an explanation that the simultaneous
      enforcement of mechanical constraints for motion and force reduces the set of
      feasible motor commands sufficiently so that force-velocity properties cease to
      be the force-limiting factor. While additional work is necessary to reveal the
      governing mechanisms, the dramatic influence that the simultaneous enforcement of
      motion and force constraints has on force output begins to explain the
      vulnerability of dexterous function to development, aging, and even mild
      neuromuscular pathology.

PMID- 19587284
TI  - Minute effects of sex on the aging brain: a multisample magnetic resonance
      imaging study of healthy aging and Alzheimer's disease.
AB  - Age is associated with substantial macrostructural brain changes. While some
      recent magnetic resonance imaging studies have reported larger age effects in men
      than women, others find no sex differences. As brain morphometry is a potentially
      important tool in diagnosis and monitoring of age-related neurological diseases,
      e.g., Alzheimer's disease (AD), it is important to know whether sex influences
      brain aging. We analyzed cross-sectional magnetic resonance scans from 1143
      healthy participants from seven subsamples provided by four independent research
      groups. In addition, 96 patients with mild AD were included. Estimates of
      cortical thickness continuously across the brain surface, as well as volume of 17
      subcortical structures, were obtained by use of automated segmentation tools
      (FreeSurfer). In the healthy participants, no differences in aging slopes between
      women and men were found in any part of the cortex. Pallidum corrected for
      intracranial volume showed slightly higher age correlations for men. The analyses
      were repeated in each of the seven subsamples, and the lack of age x sex
      interactions was largely replicated. Analyses of the AD sample showed no
      interactions between sex and age for any brain region. We conclude that sex has
      negligible effects on the age slope of brain volumes both in healthy participants
      and in AD.

PMID- 19587286
TI  - The gad2 promoter is a transcriptional target of estrogen receptor (ER)alpha and
      ER beta: a unifying hypothesis to explain diverse effects of estradiol.
AB  - Estradiol (E(2)) regulates a wide range of neural functions, many of which
      require activation of estrogen receptor alpha (ERalpha) and/or ERbeta, ligand
      gated transcriptional regulators. Surprisingly, very few neural gene targets of
      ERs have been identified, and these cannot easily explain the myriad effects of
      E(2). GABA regulates most of the same neural functions as E(2), and GABAergic
      neurons throughout the brain contain ER. Therefore, we examined whether E(2)
      directly regulates expression of glutamic acid decarboxylase 2 (gad2), the enzyme
      primarily responsible for GABA synthesis for synaptic release. Using dual
      luciferase assays, we found that E(2), but not other gonadal steroids, stimulated
      the activity of a 2691 bp rat gad2 promoter reporter construct. Activation
      required either ERalpha or ERbeta, and ERbeta did not repress ERalpha-mediated
      transactivation. Site-directed mutagenesis studies identified three estrogen
      response elements (EREs) with cell-specific functions. An ERE at -711 upstream of
      the gad2 translational start site was essential for transactivation in both MCF-7
      breast cancer cells and SN56.B5.G4 neural cells, but an ERE at -546 enhanced
      transcription only in neural cells. A third ERE at -1958 was inactive in neural
      cells but exerted potent transcriptional repression in E(2)-treated MCF-7 cells.
      Chromatin immunoprecipitation assays in mouse GABAergic N42 cells confirmed that
      E(2) induced ERalpha binding to a DNA fragment containing sequences corresponding
      to the -546 and -711 EREs of the rat promoter. Based on these data, we propose
      that direct transcriptional regulation of gad2 may explain, at least in part, the
      ability of E(2) to impact such a diverse array of neural functions.

PMID- 19587287
TI  - Role of calcitonin gene-related peptide in light-aversive behavior: implications
      for migraine.
AB  - Migraine is a chronic neurological disorder characterized by recurrent episodes
      of severe unilateral throbbing head pain and associated symptoms, such as
      photophobia. Our current understanding of the mechanisms underlying migraine has
      been hampered by limitations in ascertaining migraine symptoms in animal models.
      Clinical studies have established the neuropeptide calcitonin gene-related
      peptide (CGRP) as a key player in migraine. Here, we establish a genetic model of
      photophobia by engineering increased sensitivity to CGRP in mice. These
      transgenic mice (nestin/hRAMP1) display light-aversive behavior that is greatly
      enhanced by intracerebroventricular injection of CGRP and blocked by
      coadministration of the CGRP receptor antagonist olcegepant. This behavior
      appears to be an indicator of photophobia and cannot be fully explained by gross
      abnormality of ocular anatomy or differences in general anxiety or motor
      activity. Our findings demonstrate that a single gene, receptor activity
      modifying protein 1 (RAMP1), can be a modifier of photophobia and, by extension,
      suggest that genetic or epigenetic modulation of RAMP1 levels may contribute to
      migraine susceptibility. Moreover, they validate CGRP hypersensitive mice as a
      tool for exploring the neurobiology and novel therapies for migraine and other
      disorders involving photophobia.

PMID- 19587289
TI  - Activity-dependent codevelopment of the corticospinal system and target
      interneurons in the cervical spinal cord.
AB  - Corticospinal tract (CST) connections to spinal interneurons are conserved across
      species. We identified spinal interneuronal populations targeted by the CST in
      the cervical enlargement of the cat during development. We focused on the periods
      before and after laminar refinement of the CST terminations, between weeks 5 and
      7. We used immunohistochemistry of choline acetyltransferase (ChAT), calbindin,
      calretinin, and parvalbumin to mark interneurons. We first compared interneuron
      marker distribution before and after CST refinement. ChAT interneurons increased,
      while calbindin interneurons decreased during this period. No significant changes
      were noted in parvalbumin and calretinin. We next used anterograde labeling to
      determine whether the CST targets different interneuron populations before and
      after the refinement period. Before refinement, the CST terminated sparsely where
      calbindin interneurons were located and spared ChAT interneurons. After
      refinement, the CST no longer terminated in calbindin-expressing areas but did so
      where ChAT interneurons were located. Remarkably, early CST terminations were
      dense where ChAT interneurons later increased in numbers. Finally, we determined
      whether corticospinal system activity was necessary for the ChAT and calbindin
      changes. We unilaterally inactivated M1 between weeks 5 and 7 by muscimol
      infusion. Inactivation resulted in a distribution of calbindin and ChAT in spinal
      gray matter regions where the CST terminates that resembled the immature more
      than mature pattern. Our results show that the CST plays a crucial role in
      restructuring spinal motor circuits during development, possibly through trophic
      support, and provide strong evidence for the importance of connections with key
      spinal interneuron populations in development of motor control functions.

PMID- 19587288
TI  - Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive
      deficits and synaptic pathology in a mouse model of Alzheimer's disease.
AB  - It has been recently shown that the Alzheimer's disease (AD) pathogenic peptide
      amyloid beta(1-42) (Abeta(1-42)) binds to the alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR) with high affinity and the alpha7nAChR and Abeta(1-42) are
      both found colocalized in neuritic plaques of human brains with AD. Moreover, the
      intraneuronal accumulation of Abeta(1-42) was shown to be facilitated by its high
      affinity binding to the alpha7nAChR, and alpha7nAChR activation mediates Abeta
      induced tau protein phosphorylation. To test the hypothesis that alpha7nAChRs are
      involved in AD pathogenesis, we used a transgenic mouse model of AD
      overexpressing a mutated form of the human amyloid precursor protein (APP) and
      lacking the alpha7nAChR gene (APPalpha7KO). We have shown that, despite the
      presence of high amounts of APP and amyloid deposits, deleting the alpha7nAChR
      subunit in the mouse model of AD leads to a protection from the dysfunction in
      synaptic integrity (pathology and plasticity) and learning and memory behavior.
      Specifically, APPalpha7KO mice express APP and Abeta at levels similar to APP
      mice, and yet they were able to solve a cognitive challenge such as the Morris
      water maze test significantly better than APP, with performances comparable to
      control groups. Moreover, deleting the alpha7nAChR subunit protected the brain
      from loss of the synaptic markers synaptophysin and MAP2, reduced the gliosis,
      and preserved the capacity to elicit long-term potentiation otherwise deficient
      in APP mice. These results are consistent with the hypothesis that the
      alpha7nAChR plays a role in AD and suggest that interrupting alpha7nAChR function
      could be beneficial in the treatment of AD.

PMID- 19587290
TI  - Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1
      mediates neuroprotection against normoxic oxidative death via HIF- and CREB
      independent pathways.
AB  - Oxidative stress contributes to tissue injury in conditions ranging from
      cardiovascular disease to stroke, spinal cord injury, neurodegeneration, and
      perhaps even aging. Yet the efficacy of antioxidants in human disease has been
      mixed at best. We need a better understanding of the mechanisms by which
      established antioxidants combat oxidative stress. Iron chelators are well
      established inhibitors of oxidative death in both neural and non-neural tissues,
      but their precise mechanism of action remains elusive. The prevailing but not
      completely substantiated view is that iron chelators prevent oxidative injury by
      suppressing Fenton chemistry and the formation of highly reactive hydroxyl
      radicals. Here, we show that iron chelation protects, rather unexpectedly, by
      inhibiting the hypoxia-inducible factor prolyl 4-hydroxylase isoform 1 (PHD1), an
      iron and 2-oxoglutarate-dependent dioxygenase. PHD1 and its isoforms 2 and 3 are
      best known for stabilizing transcriptional regulators involved in hypoxic
      adaptation, such as HIF-1alpha and cAMP response element-binding protein (CREB).
      Yet we find that global hypoxia-inducible factor (HIF)-PHD inhibition protects
      neurons even when HIF-1alpha and CREB are directly suppressed. Moreover, two
      global HIF-PHD inhibitors continued to be neuroprotective even in the presence of
      diminished HIF-2alpha levels, which itself increases neuronal susceptibility to
      oxidative stress. Finally, RNA interference to PHD1 but not isoforms PHD2 or PHD3
      prevents oxidative death, independent of HIF activation. Together, these studies
      suggest that iron chelators can prevent normoxic oxidative neuronal death through
      selective inhibition of PHD1 but independent of HIF-1alpha and CREB; and that HIF
      2alpha, not HIF-1alpha, regulates susceptibility to normoxic oxidative neuronal
      death.

PMID- 19587291
TI  - Congruence of BOLD response across intertemporal choice conditions: fictive and
      real money gains and losses.
AB  - Intertemporal choice is predicated on the valuation of commodities with respect
      to delay until their receipt. Subjective value of a future outcome decreases, or
      is discounted, as a function of that delay (Bickel and Johnson, 2003). Although
      behavioral studies suggest no difference between the devaluation of real and
      fictive outcomes, no neuroimaging studies have investigated potential differences
      in the underlying deliberative process. Here, we compare behavioral and neural
      correlates of intertemporal valuation of real and hypothetical monetary gains as
      well as hypothetical losses, which have been posited to involve different
      mechanisms. Behavioral and neuroimaging sessions were conducted in which
      participants made intertemporal choice decisions in a gains condition using both
      real and hypothetical $100 money and in a loss condition using a fictive $100
      money. Within-subject comparison of behavioral data revealed no significant
      difference between levels of discounting across the three conditions. Random
      effects analysis of functional magnetic resonance imaging (fMRI) data of each of
      the three discounting conditions independently revealed significant signal change
      in limbic (anterior cingulate, striatum, posterior cingulate) and executive
      functioning areas (lateral prefrontal cortex), whereas a repeated-measures ANOVA
      failed to detect differences in signal change across the three discounting
      conditions after correcting for multiple comparisons. These data support a
      concordance between real and hypothetical conditions from delay-discounting
      studies and further suggest a congruence of the fMRI blood oxygen level-dependent
      signal across brain regions associated with the deliberative process of different
      forms of intertemporal choice.

PMID- 19587292
TI  - Postnatal expression pattern of HCN channel isoforms in thalamic neurons:
      relationship to maturation of thalamocortical oscillations.
AB  - Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are the
      molecular substrate of the hyperpolarization-activated inward current (I(h)).
      Because the developmental profile of HCN channels in the thalamus is not well
      understood, we combined electrophysiological, molecular, immunohistochemical, EEG
      recordings in vivo, and computer modeling techniques to examine HCN gene
      expression and I(h) properties in rat thalamocortical relay (TC) neurons in the
      dorsal part of the lateral geniculate nucleus and the functional consequence of
      this maturation. Recordings of TC neurons revealed an approximate sixfold
      increase in I(h) density between postnatal day 3 (P3) and P106, which was
      accompanied by significantly altered current kinetics, cAMP sensitivity, and
      steady-state activation properties. Quantification on tissue levels revealed a
      significant developmental decrease in cAMP. Consequently the block of basal
      adenylyl cyclase activity was accompanied by a hyperpolarizing shift of the I(h)
      activation curve in young but not adult rats. Quantitative analyses of HCN
      channel isoforms revealed a steady increase of mRNA and protein expression levels
      of HCN1, HCN2, and HCN4 with reduced relative abundance of HCN4. Computer
      modeling in a simplified thalamic network indicated that the occurrence of
      rhythmic delta activity, which was present in the EEG at P12, differentially
      depended on I(h) conductance and modulation by cAMP at different developmental
      states. These data indicate that the developmental increase in I(h) density
      results from increased expression of three HCN channel isoforms and that isoform
      composition and intracellular cAMP levels interact in determining I(h) properties
      to enable progressive maturation of rhythmic slow-wave sleep activity patterns.

PMID- 19587293
TI  - Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination.
AB  - How membrane biosynthesis and homeostasis is achieved in myelinating glia is
      mostly unknown. We previously reported that loss of myotubularin-related protein
      2 (MTMR2) provokes autosomal recessive demyelinating Charcot-Marie-Tooth type 4B1
      neuropathy, characterized by excessive redundant myelin, also known as myelin
      outfoldings. We generated a Mtmr2-null mouse that models the human neuropathy. We
      also found that, in Schwann cells, Mtmr2 interacts with Discs large 1 (Dlg1), a
      scaffold involved in polarized trafficking and membrane addition, whose
      localization in Mtmr2-null nerves is altered. We here report that, in Schwann
      cells, Dlg1 also interacts with kinesin 13B (kif13B) and Sec8, which are involved
      in vesicle transport and membrane tethering in polarized cells, respectively.
      Taking advantage of the Mtmr2-null mouse as a model of impaired membrane
      formation, we provide here the first evidence for a machinery that titrates
      membrane formation during myelination. We established Schwann cell/DRG neuron
      cocultures from Mtmr2-null mice, in which myelin outfoldings were reproduced and
      almost completely rescued by Mtmr2 replacement. By exploiting this in vitro
      model, we propose a mechanism whereby kif13B kinesin transports Dlg1 to sites of
      membrane remodeling where it coordinates a homeostatic control of myelination.
      The interaction of Dlg1 with the Sec8 exocyst component promotes membrane
      addition, whereas with Mtmr2, negatively regulates membrane formation. Myelin
      outfoldings thus arise as a consequence of the loss of negative control on the
      amount of membrane, which is produced during myelination.

PMID- 19587295
TI  - And yet they move: the impact of direction of deviance on stereotype change.
AB  - In 4 studies the authors compared the effect of exemplars that deviate from the
      prototype in one or the other direction while controlling for the absolute amount
      of deviance. Incongruent exemplars typically do not change a stereotype. Yet, it
      is unclear whether this is also the case with exemplars that are more extreme
      than the stereotype, named supercongruent hereafter. Within Study 1 the authors
      showed that supercongruent exemplars can be differentiated from congruent
      exemplars and that they are perceived as more typical than incongruent exemplars.
      Study 2 demonstrated that supercongruent exemplars increase the perceived
      differences between groups, while incongruent exemplars do not lead to a
      decrease. In Study 3, a supercongruent exemplar was generalized to the
      stereotype, while an incongruent exemplar did not affect the stereotype. Study 4
      replicated this finding and excluded the alternative hypothesis that this effect
      is due to the greater extremity and thus diagnosticity of supercongruent
      information.

PMID- 19587294
TI  - Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein.
AB  - Using mass spectrometry, we identified ADAM10 (a membrane-associated
      metalloproteinase) as a partner for TSPAN12, a tetraspanin protein. TSPAN12
      ADAM10 interaction was confirmed by reciprocal coimmunoprecipitation in multiple
      tumor cell lines. TSPAN12, to a greater extent than other tetraspanins (CD81,
      CD151, CD9, and CD82), associated with ADAM10 but not with ADAM17. Overexpression
      of TSPAN12 enhanced ADAM10-dependent shedding of amyloid precursor protein (APP)
      in MCF7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. Conversely, siRNA
      ablation of endogenous TSPAN12 markedly diminished APP proteolysis in both cell
      lines. Furthermore, TSPAN12 overexpression enhanced ADAM10 prodomain maturation,
      whereas TSPAN12 ablation diminished ADAM10 maturation. A palmitoylation-deficient
      TSPAN12 mutant failed to associate with ADAM10, inhibited ADAM10-dependent
      proteolysis of APP, and inhibited ADAM10 maturation, most likely by interfering
      with endogenous wild-type TSPAN12. In conclusion, TSPAN12 serves as a novel and
      robust partner for ADAM10 and promotes ADAM10 maturation, thereby facilitating
      ADAM10-dependent proteolysis of APP. This novel mode of regulating APP cleavage
      is of relevance to Alzheimer's disease therapy.

PMID- 19587296
TI  - Blame attribution as a moderator of perceptions of sexual orientation-based hate
      crimes.
AB  - Blame attribution is a valuable mechanism explaining decision making. However,
      present literature mainly employs blame attribution as a dependent variable. The
      shortcoming of this fact is that blame attribution offers a potentially valuable
      explanatory mechanism for decision making. The authors designed two studies to
      investigate blame attribution as a moderator of sentencing decisions in sexual
      orientation-based hate crimes. Study 1 showed that mock jurors punished
      perpetrators of hate crimes more severely than a control condition. Also, degree
      of victim blame influenced punitive decision making. In Study 2, mock jurors
      extended findings that perpetrators of hate crimes are more harshly punished than
      those of other types of crimes. Victim and perpetrator blame failed to moderate
      decision making in this more complex scenario. Results are discussed in relation
      to hate crimes definitions and attribution theory.

PMID- 19587297
TI  - Domestic violence against married women in Edirne.
AB  - The aim of this study is to assess the prevalence and risk factors of domestic
      violence against married women in Edirne, Turkey. This is a cross-sectional study
      which included a representative sample of the married women living in the
      Provincial Center of Edirne. The total past year prevalence of some forms of
      physical domestic violence is 34% in the last 12 months. 93% of women reported
      that they have been experiencing different forms of verbal and psychological
      domestic violence. The important risk factors for physical domestic violence were
      being Roma woman (OR = 2.97, 95% CI: 1.44-6.12), living with more than four
      people in the household (OR = 2.29, 95% CI: 1.21-4.36), being unemployed (OR =
      2.15, 95% CI: 1.06-4.37), and got married only with her families' decision (OR =
      4.60, 95% CI: 1.42-14.80). Our findings conclude that patriarchal and traditional
      values, women's lack of financial autonomy, and low socioeconomic status are the
      risk factors for physical domestic violence.

PMID- 19587298
TI  - Rapid and highly sensitive neuraminidase subtyping of avian influenza viruses by
      use of a diagnostic DNA microarray.
AB  - Rapid neuraminidase subtyping of avian influenza viruses from diagnostic samples
      is crucial considering the existence of permanently emerging and evolving
      strains. Here we report an easy-to-use, low-cost microarray for neuraminidase
      subtyping following fragment amplification by a generic, neuraminidase-specific
      reverse transcription-PCR (RT-PCR). This method enables highly specific
      characterization with a sensitivity equal to that of matrix gene-specific real
      time RT-PCR.

PMID- 19587300
TI  - False-negative results obtained with the Gen-Probe Amplified Mycobacterium
      tuberculosis direct test caused by unrecognized inhibition of the amplification
      reaction.
AB  - The Gen-Probe Amplified Mycobacterium tuberculosis direct test is widely used in
      the diagnosis of tuberculosis. Specimens may contain amplification inhibitors,
      potentially leading to false-negative results if unrecognized. We report a
      failure to detect inhibition, despite adherence to the inhibition testing
      guidelines provided on the label, and recommend changes.

PMID- 19587299
TI  - Association between contaminated faucets and colonization or infection by
      nonfermenting gram-negative bacteria in intensive care units in Taiwan.
AB  - This study was designed to determine the strength of the association between the
      isolation of nonfermentative gram-negative bacilli (NFGNB) from tap water faucet
      aerators and the prevalence of colonization or infection of patients in intensive
      care units (ICUs). Surveillance cultures were obtained during a 4-month period
      from 162 faucet aerators located in seven different ICUs. The prevalence of
      colonization or infection of ICU patients with NFGNB was determined by
      prospective surveillance during the same period. Fifty four (33%) of the faucet
      aerators contained NFGNB. Among the 66 NFGNB isolated from faucet aerators, the
      most frequently encountered ones were Sphingomonas paucimobili (26 isolates),
      Pseudomonas aeruginosa (14 isolates), Chryseobacterium meningosepticum (13
      isolates), Achromobacter xylosoxidans (6 isolates), Burkholderia cepacia (4
      isolates), and Stenotrophomonas maltophilia (3 isolates). Acinetobacter baumannii
      was not recovered. The most common NFGNB isolated from ICU patients were P.
      aeruginosa and A. baumannii. There was a significant correlation between the
      overall prevalence of NFGNB in faucet aerators and their prevalence in exposed
      ICU patients (Spearman r = 0.821, P = 0.02). There was also a significant
      correlation between the prevalence of C. meningosepticum in faucet aerators and
      its prevalence among ICU patients (Spearman r = 0.847, P = 0.016). The
      electrokaryotypes of four clinical isolates of C. meningosepticum were similar to
      those of faucet isolates. Measures directed at making the water supply safe may
      prevent infection by C. meningosepticum and other waterborne pathogens.

PMID- 19587301
TI  - Prevalence of CTX-M beta-lactamases in Philadelphia, Pennsylvania.
AB  - CTX-M beta-lactamases were thought to be rare in the United States, but a recent
      study in Texas showed that up to 70% of extended-spectrum beta-lactamase (ESBL)
      containing members of the Enterobacteriaceae family were CTX-M positive (J. S.
      Lewis, M. Herrera, B. Wickes, J. E. Patterson, and J. H. Jorgensen, Antimicrob.
      Agents Chemother. 51:4015-4021, 2007). We used PCR to detect CTX-M in all 291
      extended-spectrum cephalosporin-resistant gram-negative bacteria isolated in our
      laboratory during 2007. Thirty (48%) Escherichia coli isolates, 6 (3%) Klebsiella
      sp. isolates, and 7 (100%) Proteus mirabilis isolates tested were CTX-M positive,
      with 15% of all Enterobacteriaceae tested being positive. The E. coli CTX-M
      groups were I (57%), IV (37%), II (3%), and not groupable (3%); three of the
      group IV isolates were positive for CTX-M-18, and three of the group I isolates
      were positive for CTX-M-15. One of seven positive P. mirabilis isolates was in
      group II, with the remainder being positive for a CTX-M-25-like beta-lactamase;
      and 33% of the Klebsiella sp. isolates were in group I or IV, with the remainder
      not being in groups I to IV. CTX-M-producing bacteria were isolated from urine (n
      = 13), blood (n = 13), wounds (n = 12), and the respiratory tract (n = 4). All 31
      CTX-M-positive isolates tested for the presence of ESBL were confirmed to produce
      ESBLs by the use of tests recommended by the CLSI. Pulsed-field gel
      electrophoresis of the CTX-M-positive isolates showed that six P. mirabilis
      isolates were clonal and that there were seven different E. coli clusters. Five
      of seven P. mirabilis isolates were from blood cultures. The CLSI tests for the
      confirmation of ESBL production reliably detect these isolates if both cefotaxime
      and ceftazidime are tested, but only about half would be classified as a possible
      CTX-M producers on the basis of the antibiogram alone. A new panprimer set
      increases the ability to detect CTX-M-producing strains. CTX-M-positive bacteria
      are common in our geographic region, are often invasive, and, with the exception
      of P. mirabilis, are multiclonal.

PMID- 19587302
TI  - Development of a multilocus microsatellite typing approach for discriminating
      strains of Leishmania (Viannia) species.
AB  - A multilocus microsatellite typing (MLMT) approach based on the analysis of 15
      independent loci has been developed for the discrimination of strains belonging
      to different Viannia species. Thirteen microsatellite loci were isolated de novo
      from microsatellite-enriched libraries for both Leishmania braziliensis and L.
      guyanensis. Two previously identified markers, AC01 and AC16, were modified and
      added to our marker set. Markers were designed to contain simple dinucleotide
      repeats flanked by the minimal possible number of nucleotides in order to allow
      variations in repeat numbers to be scored as size variations of the PCR products.
      The 15 markers in total were amplified for almost all of the strains of Viannia
      tested; one marker did not amplify from the two L. peruviana strains included in
      the study. When 30 strains of L. braziliensis, 21 strains of L. guyanensis, and 2
      strains of L. peruviana were tested for polymorphisms, all strains except two
      strains of L. guyanensis had individual MLMT types. Distance-based analysis
      identified three main clusters. All strains except one strain of L. guyanensis
      grouped together. Two clusters consisted of strains of L. braziliensis according
      to their geographical origins. The two strains of L. peruviana grouped together
      with strains of L. braziliensis from Peru and the adjacent Brazilian state of
      Acre. MLMT has proven capable of individualizing strains even from the same areas
      of endemicity and of detecting genetic structures at different levels. MLMT is
      thus applicable for epidemiological and population genetic studies of strains
      within the subgenus Viannia.

PMID- 19587304
TI  - Rapid method to support diagnosis of swine origin influenza virus infection by
      sequencing of real-time PCR amplicons from diagnostic assays.

PMID- 19587303
TI  - Subtype analysis of Cryptosporidium specimens from sporadic cases in Colorado,
      Idaho, New Mexico, and Iowa in 2007: widespread occurrence of one Cryptosporidium
      hominis subtype and case history of an infection with the Cryptosporidium horse
      genotype.
AB  - Subtyping was conducted in late 2007 on 57 Cryptosporidium specimens from
      sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare
      Cryptosporidium hominis subtype was identified in 40 cases (70%) from all four
      states, and the Cryptosporidium horse genotype was identified in a pet shop
      employee with severe clinical symptoms.

PMID- 19587305
TI  - Stable polymyxin B susceptibility to Pseudomonas aeruginosa and Acinetobacter
      spp. despite persistent recovery of these organisms from respiratory secretions
      of patients with ventilator-associated pneumonia treated with this drug.

PMID- 19587306
TI  - Field performance of a rapid diagnostic test for influenza in an ambulatory
      setting.
AB  - Provided test characteristics are adequate, point-of-care rapid antigen detection
      tests for influenza could improve the timeliness and appropriateness of clinical
      decisions. Our objective was to estimate the field sensitivity and specificity of
      the Quidel QuickVue Influenza A+B test in an ambulatory setting. The sensitivity
      and specificity of the Quidel QuickVue test was evaluated against reverse
      transcriptase PCR (RT-PCR) on nasopharyngeal specimens collected over two
      consecutive influenza seasons from ambulatory patients consulting for influenza
      like illness (ILI) within 7 days of ILI onset. A total of 491 patients with ILI
      (180 in 2006 to 2007 and 311 in 2007 to 2008) provided specimens that were tested
      both by PCR and by the Quidel QuickVue test. Among the 267 patients positive by
      PCR (55%), 52 were also positive by the QuickVue test, for an overall sensitivity
      of 19.5% (95% confidence interval [95% CI], 14.7% to 24.2%). Among the 221 PCR
      negative patients, 2 were positive for influenza B virus by the rapid test (<1%),
      for an overall specificity of 99.1% (95% CI, 97.9 to 100%). The field sensitivity
      of the test varied little with the age or gender of the patient, immunization
      status, delay since the onset of symptoms, or influenza season. The sensitivity
      of the test was slightly but nonsignificantly higher for influenza B virus (23%)
      than for influenza A virus (18%). Despite its high specificity, the low
      sensitivity of the Quidel QuickVue Influenza A+B test is too poor to direct
      clinical decisions for ambulatory patients with ILI. Negative results cannot rule
      out the diagnosis of influenza, and in that context, this test is of questionable
      utility for routine application in the clinical setting.

PMID- 19587307
TI  - Endoscopic third ventriculostomy: predicting outcome with phase-contrast MR
      imaging.
AB  - PURPOSE: To determine whether phase-contrast magnetic resonance (MR) imaging
      measurements of preoperative cerebral blood and cerebrospinal fluid (CSF)
      hydrodynamics can be used as a biomarker of response to endoscopic third
      ventriculostomy (ETV). MATERIALS AND METHODS: Approval from the local research
      ethics committee and written informed consent were obtained for this prospective
      study. Thirteen patients (six female patients, seven male patients; median age,
      43 years) with chronic obstructive hydrocephalus, 12 of whom went on to undergo
      ETV, were imaged with phase-contrast MR imaging at 1.5 T to determine rates of
      total cerebral blood flow (CBF) and ventriculostomy defect, foramen magnum (FM),
      and cerebral aqueduct CSF flow. Ten control subjects (10 men; median age, 37
      years) were similarly imaged. Correlations between measured values were assessed
      by means of Pearson correlation coefficients. Measurements were compared between
      groups with a Mann-Whitney test, and measurements before and after surgical
      intervention were compared with a Wilcoxon test for paired samples. RESULTS:
      Rates of CBF (356 mL . min(-1) +/- 73 [standard deviation] vs 518 mL . min(-1) +/
      79, P < .001) and CSF flow in the FM (17.62 mL . min(-1) +/- 13.12 vs 36.35 mL .
      min(-1) +/- 8, P < .05) were significantly lower in patients than in control
      subjects. CONCLUSION: ETV induces changes in brain volume and CBF that can be
      predicted by using simple metrics. These pilot results support a formal trial of
      these techniques in a larger prospective study.

PMID- 19587308
TI  - Early detection of steatohepatitis in fatty rat liver by using MR elastography.
AB  - PURPOSE: To assess the potential value of magnetic resonance (MR) elastographic
      imaging to help detect nonalcoholic steatohepatitis in the fatty rat liver.
      MATERIALS AND METHODS: This study was approved by the regional ethics committee.
      Fifty-four rats were imaged after being fed either a standard diet, a choline
      deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic
      acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride
      injection to model acute liver injury. MR elastography was performed at 7.0 T to
      assess viscoelastic liver parameters. Steatosis and fibrosis were quantified with
      morphometric and biochemical analysis. Myofibroblast activation was assessed with
      morphometric analysis of alpha-smooth muscle actin. Expression of transforming
      growth factor beta1 and procollagens 1 and 3 as markers of fibrogenesis was
      evaluated with real-time reverse transcription polymerase chain reaction.
      Inflammation was scored at histologic analysis. RESULTS: In rats with
      steatohepatitis, mean elasticity (2.24 kPa +/- 0.19 [standard deviation] vs 1.82
      kPa +/- 0.22) and mean viscosity (0.86 kPa +/- 0.10 vs 0.59 kPa +/- 0.12)
      increased significantly (P < .005) after the 2-week orotic acid diet, while
      steatosis, inflammation, myofibroblast activation, and increase of other
      fibrogenesis markers were observed. Fibrosis appeared only after 5 weeks. In rats
      with steatosis, viscosity increased (0.77 kPa +/- 0.11, P < .005), elasticity
      remained constant. In rats with acute liver injury, elasticity (2.96 kPa +/-
      0.63) and viscosity (0.85 kPa +/- 0.22) increased (P < .005), while fibrogenesis
      and inflammation were observed without substantial fibrosis or steatosis. At
      multivariate analysis in all rats, liver elasticity correlated only with
      myofibroblast activation (P < .001, r > 0.6). CONCLUSION: The results suggest
      that in nonalcoholic fatty rat liver, MR elastography may be useful in the early
      detection of steatohepatitis by showing increased elasticity and appearing before
      fibrosis development, which was linked to myofibroblast activation. SUPPLEMENTAL
      MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2523081817/
      /DC1.

PMID- 19587309
TI  - Neuro-lyme disease: MR imaging findings.
AB  - PURPOSE: To describe the neuroimaging manifestations of Lyme disease at magnetic
      resonance (MR) imaging of the brain. MATERIALS AND METHODS: Institutional review
      board approval was obtained and HIPAA compliance was followed. This study
      retrospectively reviewed the MR imaging findings of all patients seen from 1993
      to 2007 in whom neuro-Lyme disease was suspected and who were referred for MR
      imaging of the brain for the evaluation of neurologic symptoms. RESULTS: Of 392
      patients suspected of having neuro-Lyme disease, 66 patients proved to have the
      disease on the basis of clinical criteria, serologic results, and response to
      treatment. Seven of these 66 patients showed foci of T2 prolongation in the
      cerebral white matter, one had an enhancing lesion with edema, and three
      demonstrated nerve-root or meningeal enhancement. Of the seven patients with foci
      of T2 prolongation in the white matter, three were an age at which white matter
      findings due to small-vessel disease are common. CONCLUSION: In cases of nerve
      root or meningeal enhancement, Lyme disease should be considered in the
      differential diagnosis in the proper clinical setting.

PMID- 19587310
TI  - In vivo functional and anatomic imaging for assessment of in vivo gene transfer.
AB  - PURPOSE: To assess whether a combination of in vivo anatomic and functional
      imaging can help quantify expression of somatostatin receptor type 2 (SSTR2)
      based reporters after in vivo gene transfer. MATERIALS AND METHODS: All animal
      experiments were approved by an institutional animal care and use committee. Six
      nude mice bearing two subcutaneous L3.6pl (human pancreatic cancer) tumors were
      injected intratumorally with an adenovirus containing a human somatostatin
      receptor type 2 gene chimera (Ad-HA-SSTR2) or a control adenovirus containing
      green fluorescent protein (Ad-GFP). Two days later, magnetic resonance (MR)
      imaging was performed to derive tumor weight and analyze morphology. Intravenous
      injection of Food and Drug Administration-approved indium 111 octreotide was
      followed by gamma camera imaging (planar imaging and single photon emission
      computed tomography [SPECT]) the next day. Region-of-interest analysis followed.
      The procedure was also performed in six nude mice with slow-growing MDA-MB-435
      (human breast carcinoma) tumors, which allowed serial imaging 3 days and 2 weeks
      after adenovirus injection. After imaging, excised tumor weight and
      biodistribution were assessed. Statistical analyses included a Student t test and
      linear regression. RESULTS: With both tumor types, ex vivo and image-based in
      vivo biodistribution demonstrated greater uptake (percentage of injected dose per
      gram) in tumors infected with Ad-HA-SSTR2 than in those infected with Ad-GFP (P <
      .05). Furthermore, in vivo and ex vivo biodistribution analysis correlated (ex
      vivo vs planar and MR imaging: r = 0.87, P < .05, n = 24; ex vivo vs SPECT and MR
      imaging: r = 0.84, P < .05, n = 24). Moreover, in vivo biodistribution
      distinguished greater expression at the earlier time point in MDA-MB-435 tumors
      infected with Ad-HA-SSTR2 from waning expression at the later time point (P <
      .05). CONCLUSION: A combination of in vivo functional and anatomic imaging
      methods can help quantify gene expression after in vivo gene transfer.

PMID- 19587311
TI  - Dual-source versus 64-section CT coronary angiography at lower heart rates:
      comparison of accuracy and radiation dose.
AB  - PURPOSE: To compare the diagnostic performance and radiation doses of dual-source
      and 64-section computed tomographic (CT) coronary angiography for the diagnosis
      of significant coronary stenoses in patients with heart rates of 65 beats/min or
      less. MATERIALS AND METHODS: This retrospective study had local ethics committee
      approval; all patients gave written informed consent. Two hundred patients with
      heart rates of 65 beats/min or less were enrolled; 100 underwent dual-source and
      100 underwent 64-section CT coronary angiography. Two blinded observers
      independently assessed image quality of all coronary segments by using a four
      point scale and searched for significant (>50%) stenoses in each segment.
      Catheter angiography was used as the reference standard. Image noise was measured
      in the ascending aorta. Radiation doses were calculated. RESULTS: No significant
      differences were found regarding sex, age, body weight, cardiovascular risk
      profile, prevalence of stenosis, mean and variability of heart rate, Agatston
      score, and image noise (all P > .1) between patients in both CT coronary
      angiography groups. No significant difference was found in the rate of
      nonassessable coronary segments between dual-source (1.0%, 14 of 1405) and 64
      section CT coronary angiography (1.8%, 25 of 1387; P = .08). Motion artifacts
      occurred significantly more often in 64-section (21 of 25) versus dual-source
      (five of 14, P = .004) CT coronary angiography. Segment-based accuracy and
      specificity were significantly higher for dual-source versus 64-section CT
      coronary angiography. There was no significant difference in accuracy parameters
      at the per-vessel and per-patient analyses. No significant difference (P = .13)
      was found between the effective doses of dual-source (mean +/- standard
      deviation, 10.9 mSv +/- 1.1) and 64-section CT (10.4 mSv +/- 1.7) coronary
      angiography. CONCLUSION: In patients with heart rates of 65 beats/min or less,
      the higher temporal resolution of dual-source CT coronary angiography results in
      improved accuracy and specificity for the diagnosis of significant stenoses on a
      per-segment level at a similar radiation dose, but provides a comparable
      diagnostic accuracy on a patient-based level as does 64-section coronary
      angiography.

PMID- 19587312
TI  - Matrix metalloprotease-9 inhibition improves amyloid beta-mediated cognitive
      impairment and neurotoxicity in mice.
AB  - In Alzheimer's disease (AD), the expression of matrix metalloproteases (MMPs),
      which are capable of degrading extracellular matrix proteins, is increased in the
      brain. Previous studies with cultured glial cells have demonstrated that amyloid
      beta (Abeta) protein can induce the expression of MMPs, which could be involved
      in the degradation of Abeta. In the present study, we investigated the role of
      MMP-2 and MMP-9 in cognitive impairment induced by the injection of Abeta in
      mice. The intracerebroventricular injection of Abeta25-35, Abeta1-40, and Abeta1
      42, but not Abeta40-1, transiently increased MMP-9, but not MMP-2, activity and
      protein expression in the hippocampus. Immunohistochemistry revealed the
      expression of MMP-9 to be increased in both neurons and glial cells in the
      hippocampus after Abeta treatment. The Abeta-induced cognitive impairment in vivo
      as well as neurotoxicity in vitro was significantly alleviated in MMP-9
      homozygous knockout mice and by treatment with MMP inhibitors. These results
      suggest the increase in MMP-9 expression in the hippocampus to be involved in the
      development of cognitive impairment induced by Abeta1-40. Thus, specific
      inhibitors of MMP-9 may have therapeutic potential for the treatment of AD. Our
      findings suggest that, as opposed to expectations based on previous findings, MMP
      9 plays a causal role in Abeta-induced cognitive impairment and neurotoxicity.

PMID- 19587313
TI  - Brain AT1 angiotensin receptor subtype binding: importance of peptidase
      inhibition for identification of angiotensin II as its endogenous ligand.
AB  - The existence and localization of brain angiotensin receptors is well
      established. However, questions regarding the endogenous ligand for brain
      angiotensin type 1 (AT(1)) receptors necessitates re-examination of brain
      angiotensin receptor binding studies. To assess the ability of angiotensin II to
      bind to the brain AT(1) receptor, radioligand binding studies of rat brain AT(1)
      receptors were performed using both (125)I-angiotensin II and (125)I
      sarcosine(1), isoleucine(8) angiotensin II. Determination of binding kinetics and
      competition by an AT(1) receptor antagonist was carried out to reveal the
      identity of the membrane binding sites and to identify the bound (125)I-labeled
      molecules. Initial analysis of (125)I-angiotensin II binding to hypothalamic
      membranes using an established protocol revealed that a negligible amount of
      intact radioligand was bound to the membranes. In contrast, binding of (125)I
      sarcosine(1), isoleucine(8) angiotensin II was saturable, of high affinity, and
      primarily as intact radioligand. Sequential addition of four peptidase inhibitors
      o-phenanthroline, puromycin, phenymethylsulfonyl fluoride, and glutamate
      phosphonate-to the assay buffer dramatically increased the binding of (125)I
      angiotensin II to rat brain membranes: more than 75% of the bound (125)I was the
      intact radioligand, and the binding was of high affinity and saturable. Some, but
      not all, of the binding could be displaced by the AT(1)-selective antagonist
      losartan. This demonstrates that (125)I-angiotensin II can bind to brain AT(1)
      receptors and does not require conversion to (125)I-angiotensin III to bind to
      brain AT(1) receptors.

PMID- 19587314
TI  - Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and
      beta2-AR agonist in a rat model of postmyocardial infarction dilated heart
      failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme
      inhibitor.
AB  - We had proposed previously a novel combination of beta2-adrenoreceptor (AR)
      agonist and beta1-AR blocker that in the rat model of postmyocardial infarction
      (MI) dilated cardiomyopathy exceeds the therapeutic effectiveness of either
      monotherapy. In the present study, we compared that treatment with a combination
      of beta1-AR blocker and angiotensin-converting enzyme inhibitor (ACEi), a current
      standard chronic heart failure (CHF) therapy. Two weeks after coronary artery
      ligation, rats were divided into groups of similar average MI size, measured by
      echocardiography, and the following 12-month treatments were initiated: fenoterol
      (250 microg/kg/day), a beta2-AR agonist, plus metoprolol (100 mg/kg/day), a beta1
      AR blocker (beta1-beta2+); metoprolol plus enalapril (20 mg/kg/day), an ACEi
      (beta1-ACEi); and a combination of all three drugs (beta1-beta2+ACEi). These
      treatment groups were compared with each other and with nontreated (nT) and sham
      groups. The 12-month mortality was significantly reduced in all treatment groups
      (44% in beta1-beta2+, 56% in beta1-beta2+ACEi, 59% in beta1-ACEi versus 81% in
      nT). Bimonthly echocardiography revealed significant attenuation of the left
      ventricular (LV) chamber remodeling, LV functional deterioration, and MI
      expansion in all three treatment groups, but effects were significantly more
      pronounced when treatment included a beta2-AR agonist. The results indicated that
      a combination of beta1-AR blocker and beta2-AR agonist is equipotent to a
      combination of beta1-AR blocker and ACEi in the treatment of CHF in rats, with
      the respect to mortality, and exceeds the latter with respect to cardiac
      remodeling and MI expansion. Thus, this novel therapeutic regimen for CHF
      warrants detailed clinical investigation.

PMID- 19587315
TI  - Chronic ethanol consumption lessens the gain of body weight, liver triglycerides,
      and diabetes in obese ob/ob mice.
AB  - Clinical studies suggest that moderate alcohol consumption can have beneficial
      effects, in particular regarding cardiovascular events, insulin resistance, and
      type 2 diabetes. In this study, lean and obese diabetic ob/ob mice were submitted
      or not to chronic ethanol intake via the drinking water for 6 months, which was
      associated with moderate levels of plasma ethanol. Plasma levels of alanine
      aminotransferase and aspartate aminotransferase were not increased by alcohol
      intake. Ethanol consumption progressively reduced the gain of body weight in
      ob/ob mice, but not in lean mice, and this was observed despite higher calorie
      intake. Increased plasma free fatty acids and glycerol in ethanol-treated ob/ob
      mice suggested peripheral lipolysis. Glycemia and insulinemia were significantly
      reduced, whereas adiponectinemia was increased in ethanol-treated ob/ob mice.
      Liver weight and triglycerides were significantly decreased in ethanol-treated
      ob/ob mice, and this was associated with less microvesicular steatosis. Hepatic
      levels of AMP-activated protein kinase and the phosphorylated form of acetyl-CoA
      carboxylase were higher in ethanol-treated ob/ob mice, suggesting better fatty
      acid oxidation. However, hepatic mRNA expression of several lipogenic genes was
      not reduced by ethanol consumption. Finally, mild oxidative stress was noticed in
      the liver of ethanol-treated mice, regardless of their genotype. Hence, our data
      are in keeping with clinical studies suggesting that moderate ethanol intake can
      have beneficial effects on type 2 diabetes and insulin sensitivity, at least in
      part through increased levels of plasma adiponectin. However, further studies are
      needed to determine whether long-term drinking of light-to-moderate amounts of
      ethanol is safe for the liver.

PMID- 19587316
TI  - Optical imaging of contextual interactions in V1 of the behaving monkey.
AB  - Interactions in primary visual cortex (V1) between simple visual elements such as
      short bar segments are believed to underlie our ability to easily integrate
      contours and segment surfaces. We used intrinsic signal optical imaging in alert
      fixating macaques to measure the strength and cortical distribution of V1
      interactions among collinear bars. A single short bar stimulus produced a broad
      peaked hill of activation (the optical point spread) covering multiple
      orientation hypercolumns in V1. Flanking the bar stimulus with a pair of
      identical collinear bars led to a strong nonlinear suppression in the optical
      signal. This nonlinearity was strongest over the center bar region, with a
      spatial distribution that cannot be explained by a simple gain control. It was a
      function of the relative orientation and separation of the bar stimuli in a
      manner tuned sharply for collinearity, being strongest for immediately adjacent
      bars lying on a smooth contour. These results suggest intracortical interactions
      playing a major role in determining V1 activation by smooth extended contours.
      Our finding that the interaction is primarily suppressive when imaged optically,
      which presumably reflects the combined inhibitory and excitatory inputs, suggests
      a complex interplay between these cortical inputs leading to the collinear
      facilitation seen in the spiking response of V1 neurons. This disjuncture between
      the facilitation seen in spiking and the suppression in imaging also suggests
      that cortical representations of complex stimuli involve interactions that need
      to be studied over extended networks and may be hard to deduce from the responses
      of individual neurons.

PMID- 19587317
TI  - Heat synch: inter- and independence of body-temperature fluctuations and brain
      state alternations in urethane-anesthetized rats.
AB  - During sleep, warm-blooded animals exhibit cyclic alternations between rapid-eye
      movement (REM) and nonrapid-eye-movement (non-REM) states, characterized by
      distinct patterns of brain activity apparent in electroencephalographic (EEG)
      recordings coupled with corresponding changes in physiological measures,
      including body temperature. Recently we have shown that urethane-anesthetized
      rats display cyclic alternations between an activated state and a deactivated
      state that are highly similar in both EEG and physiological characteristics to
      REM and non-REM sleep states, respectively. Here, using intracranial local field
      potential recordings from urethane-anesthetized rats, we show that brain-state
      alternations were correlated to core temperature fluctuations induced using a
      feedback-controlled heating system. Activated (REM-like) states predominated
      during the rising phase of the temperature cycle, whereas deactivated (non-REM
      like) states predominated during the falling phase. Brain-state alternations
      persisted following the elimination of core temperature fluctuations by the use
      of a constant heating protocol, but the timing and rhythmicity of state
      alternations were altered. In contrast, thermal fluctuations applied to the
      ventral surface (and especially the scrotum) of rats in the absence or
      independently of core temperature fluctuations appeared to induce brain-state
      alternations. Heating brought about activated patterns, whereas cooling produced
      deactivated patterns. This shows that although alternations of sleeplike brain
      states under urethane anesthesia can be independent of imposed temperature
      variations, they can also be entrained through the activation of peripheral
      thermoreceptors. Overall, these results imply that brain state and bodily
      metabolism are highly related during unconsciousness and that the brain
      mechanisms underlying sleep cycling and thermoregulation likely represent
      independent, yet coupled oscillators.

PMID- 19587318
TI  - Nonlinear signal summation in magnocellular neurons of the macaque lateral
      geniculate nucleus.
AB  - Magnocellular (M-), but not parvocellular (P-), neurons of the macaque lateral
      geniculate nucleus (LGN) differ distinctively in their responses to counterphase
      modulated and drifting gratings. Relative to stimulation with drifting gratings,
      counterphase modulation reduces the responses of M- cells in a band around 25 Hz,
      producing a "notch" in the temporal modulation transfer function (tMTF). The
      notch is prominent in nearly every M- cell with little variation in the temporal
      frequency at which it is deepest. The machinery responsible for the notch lies
      mostly outside the classical linear center. Directly driving the notching
      mechanism with annular gratings evokes no linear response but elicits a second
      harmonic (F2) modulation of the discharge accompanied by a drop in the mean
      discharge (F0). Analysis of the S- potential, which reveals inputs from ganglion
      cells, shows that 1) tMTFs of the afferent retinal ganglion cells are not notched
      and 2) during stimulation with annular gratings, the second harmonic component is
      present, but the drop in the F0 is largely absent from the responses of parasol
      ganglion cells. These results suggest that the notch is caused by the combined
      action of the linear response and the second harmonic response, both inherited
      from retina, and a suppression that originates after the retina. Our results
      reveal a distinctive signal transformation in the LGN and they show that nearly
      every M- cell exhibits a spatial nonlinearity like that observed in Y cells of
      the cat.

PMID- 19587319
TI  - Neural correlates of novel object and novel location recognition behavior in the
      mouse anterior cingulate cortex.
AB  - The anterior cingulate cortex (ACC) is a component of the limbic system
      implicated in a wide variety of functions spanning motor and sensory information
      processing, memory, attention, novelty detection, and comparisons of expectation
      versus outcome. It remains unclear how much of this functional diversity stems
      from differences in methodology or interpretation versus truly reflecting the
      range of processes in which the ACC is involved. In the present study, ACC
      neuronal activity was examined in freely behaving mice (C57BL6/J) under
      conditions allowing investigation of many of the cited functions in conditions
      free from externally applied rules: tests of novel object and novel location
      recognition memory. Behavioral activity and neuronal activity were recorded first
      in the open field, during the initial exposure and subsequent familiarization to
      two identical objects, and finally during the recognition memory tests. No
      discernible stable firing correlates of ACC neurons were found in the open field,
      but the addition of objects led to lasting changes in the firing patterns of many
      ACC neurons around one or both of the object locations. During the novel location
      test, some neurons followed the familiar object to its new location, others fired
      exclusively where the object had been, and yet others fired to both current and
      former object locations. Many of these same features were observed during tests
      of object recognition memory. However, the magnitude of the neuronal preference
      for the novel or the familiar object was markedly greater than that observed
      during either the tests of location recognition or novel object preferences in
      animals that did not exhibit the expected behavior. The present study reveals,
      for the first time, single-neuron correlates of object and location recognition
      behaviors in the rodent ACC and suggests that neurons of the ACC provide a
      distributed representation of all of the salient features of a task.

PMID- 19587320
TI  - Practice-related improvement in working memory is modulated by changes in
      processing external interference.
AB  - Working memory (WM) performance is impaired by the presence of external
      interference. Accordingly, more efficient processing of intervening stimuli with
      practice may lead to enhanced WM performance. To explore the role of practice on
      the impact that interference has on WM performance, we studied young adults with
      electroencephalographic (EEG) recordings as they performed three motion
      direction, delayed-recognition tasks. One task was presented without
      interference, whereas two tasks introduced different types of interference during
      the interval of memory maintenance: distractors and interruptors. Distractors
      were to be ignored, whereas interruptors demanded attention based on task
      instructions for a perceptual discrimination. We show that WM performance was
      disrupted by both types of interference, but interference-induced disruption
      abated across a single experimental session through rapid learning. WM accuracy
      and response time improved in a manner that was correlated with changes in early
      neural measures of interference processing in visual cortex (i.e., P1 suppression
      and N1 enhancement). These results suggest practice-related changes in processing
      interference exert a positive influence on WM performance, highlighting the
      importance of filtering irrelevant information and the dynamic interactions that
      exist between neural processes of perception, attention, and WM during learning.

PMID- 19587321
TI  - Origins of abnormal excitability in biceps brachii motoneurons of spastic-paretic
      stroke survivors.
AB  - Stroke survivors often exhibit abnormal motoneuron excitability, manifested
      clinically as spasticity with exaggerated stretch reflexes in resting muscles. We
      examined whether this abnormal excitability is a result of increased activation
      of intrinsic voltage-dependent persistent inward currents (PICs) or whether it is
      a result of enhanced synaptic inputs to the motoneuron. This distinction was made
      by recording firing rate profiles of pairs of motor units during isometric
      contractions of elbow flexor muscles. To estimate PIC amplitude, the discharge of
      the lower-threshold (reporter) motor unit of the pair was used to estimate the
      synaptic input to the higher-threshold (test) motor unit. The estimated synaptic
      input required to recruit the test unit was compared with the synaptic input when
      the test unit was derecruited (DeltaF) and this served as an estimate of the
      intrinsic (PIC) contribution to motoneuron firing. We found that PIC estimates
      were not larger in spastic-paretic motoneurons (DeltaF = 4.0 +/- 1.6 pps)
      compared with contralateral (4.6 +/- 1.4 pps) and age-matched healthy control
      motoneurons (3.8 +/- 1.7, all P > 0.1). Instead, following the voluntary
      contractions, the majority of lower-threshold motor units in spastic-paretic
      muscles (83%) exhibited spontaneous discharge, compared with 14% of contralateral
      and 0% of control motor units. Furthermore, there was strong co-modulation of
      simultaneously active units in spastic muscle. The presence of ongoing,
      correlated unit activity at "rest," coupled with firing behavior at recruitment
      unique to lower-threshold motor units in spastic muscles, suggested that firing
      changes are likely a result of a low-level depolarizing synaptic drive to the
      resting motoneuron pool.

PMID- 19587322
TI  - Genetic dissection of rod and cone pathways in the dark-adapted mouse retina.
AB  - A monumental task of the mammalian retina is to encode an enormous range (>10(9)
      fold) of light intensities experienced by the animal in natural environments.
      Retinal neurons carry out this task by dividing labor into many parallel rod and
      cone synaptic pathways. Here we study the operational plan of various rod- and
      cone-mediated pathways by analyzing electroretinograms (ERGs), primarily b-wave
      responses, in dark-adapted wildtype, connexin36 knockout, depolarizing rod
      bipolar cell (DBCR) knockout, and rod transducin alpha-subunit knockout mice [WT,
      Cx36(-/-), Bhlhb4(-/-), and Tralpha(-/-)]. To provide additional insight into the
      cellular origins of various components of the ERG, we compared dark-adapted ERG
      responses with response dynamic ranges of individual retinal cells recorded with
      patch electrodes from dark-adapted mouse retinas published from other studies.
      Our results suggest that the connexin36-mediated rod-cone coupling is weak when
      light stimulation is weak and becomes stronger as light stimulation increases in
      strength and that rod signals may be transmitted to some DBCCs via direct
      chemical synapses. Moreover, our analysis indicates that DBCR responses
      contribute about 80% of the overall DBC response to scotopic light and that rod
      and cone signals contribute almost equally to the overall DBC responses when
      stimuli are strong enough to saturate the rod bipolar cell response. Furthermore,
      our study demonstrates that analysis of ERG b-wave of dark-adapted, pathway
      specific mutants can be used as an in vivo tool for dissecting rod and cone
      synaptic pathways and for studying the functions of pathway-specific gene
      products in the retina.

PMID- 19587324
TI  - Impact of synaptic depression on spike timing at the endbulb of Held.
AB  - Many synapses show short-term depression, but it is not well understood what
      functional purpose depression serves and whether its effects are beneficial or
      detrimental to information processing. We study this issue at the synapse made by
      auditory-nerve (AN) fibers onto bushy cells (BCs) of the cochlear nucleus, called
      the "endbulb of Held." AN fibers carry timing information about sounds and
      converge on BCs, which relay timing information to brain areas responsible for
      sound localization. Dynamic-clamp recordings of BCs in mouse brain slices
      indicated that nonphase-locked inputs influenced the contribution of phase-locked
      inputs when all inputs had equal strength. We evaluated whether this situation
      depended on activity-dependent synaptic plasticity. Voltage-clamp recordings
      indicated that the amount of depression varied over the population of endbulbs,
      but sibling endbulbs terminating on the same BC had similar plasticity. We tested
      the effects of endbulb depression on BC spiking using dynamic clamp. Under most
      conditions, increasing depression led to lower probability of BC spiking.
      However, the effects on spike timing were highly context dependent. When all
      inputs carried uniform timing information, depression indirectly affected BC
      spike precision, by determining how many inputs were required to cross threshold.
      Earlier work has indicated that this interacts with the temporal distribution of
      inputs to determine BC spike precision. When inputs carried different timing
      information, depression greatly improved BC precision by suppressing highly
      active inputs carrying little phase-locked information. These data suggest that
      endbulbs with different depression characteristics could produce BCs that enhance
      response probability or timing under different stimulus conditions.

PMID- 19587323
TI  - Visual field maps, population receptive field sizes, and visual field coverage in
      the human MT+ complex.
AB  - Human neuroimaging experiments typically localize motion-selective cortex (MT+)
      by contrasting responses to stationary and moving stimuli. It has long been
      suspected that MT+, located on the lateral surface at the temporal-occipital (TO)
      boundary, contains several distinct visual field maps, although only one coarse
      map has been measured. Using a novel functional MRI model-based method we
      identified two maps-TO-1 and TO-2-and measured population receptive field (pRF)
      sizes within these maps. The angular representation of the first map, TO-1, has a
      lower vertical meridian on its posterior side at the boundary with the lateral
      occipital cortex (i.e., the LO-2 portion). The angular representation continues
      through horizontal to the upper vertical meridian at the boundary with the second
      map, TO-2. The TO-2 angle map reverses from upper to lower visual field at
      increasingly anterior positions. The TO maps share a parallel eccentricity map in
      which center-to-periphery is represented in the ventral-to-dorsal direction; both
      maps have an expanded foveal representation. There is a progressive increase in
      the pRF size from V1/2/3 to LO-1/2 and TO-1/2, with the largest pRF sizes in TO
      2. Further, within each map the pRF size increases as a function of eccentricity.
      The visual field coverage of both maps extends into the ipsilateral visual field,
      with larger sensitivity to peripheral ipsilateral stimuli in TO-2 than that in TO
      1. The TO maps provide a functional segmentation of human motion-sensitive cortex
      that enables a more complete characterization of processing in human motion
      selective cortex.

PMID- 19587325
TI  - Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB
      PET study.
AB  - BACKGROUND: Patients with amnestic mild cognitive impairment (MCI) represent an
      important clinical group as they are at increased risk of developing Alzheimer
      disease (AD). (11)C-PIB PET is an in vivo marker of brain amyloid load.
      OBJECTIVE: To assess the rates of conversion of MCI to AD during a 3-year follow
      up period and to compare levels of amyloid deposition between MCI converters and
      nonconverters. METHODS: Thirty-one subjects with MCI with baseline (11)C-PIB PET,
      MRI, and neuropsychometry have been clinically followed up for 1 to 3 years (2.68
      +/- 0.6 years). Raised cortical (11)C-PIB binding in subjects with MCI was
      detected with region of interest analysis and statistical parametric mapping.
      RESULTS: Seventeen of 31 (55%) subjects with MCI had increased (11)C-PIB
      retention at baseline and 14 of these 17 (82%) clinically converted to AD during
      follow-up. Only one of the 14 PIB-negative MCI cases converted to AD. Of the PIB
      positive subjects with MCI, half (47%) converted to AD within 1 year of baseline
      PIB PET, these faster converters having higher tracer-retention values than
      slower converters in the anterior cingulate (p = 0.027) and frontal cortex (p =
      0.031). Seven of 17 (41%) subjects with MCI with known APOE status were epsilon4
      allele carriers, this genotype being associated with faster conversion rates in
      PIB-positive subjects with MCI (p = 0.035). CONCLUSIONS: PIB-positive subjects
      with mild cognitive impairment (MCI) are significantly more likely to convert to
      AD than PIB-negative patients, faster converters having higher PIB retention
      levels at baseline than slower converters. In vivo detection of amyloid
      deposition in MCI with PIB PET provides useful prognostic information.

PMID- 19587328
TI  - Vitamin A deficiency blocks the initiation of meiosis of germ cells in the
      developing rat ovary in vivo.
AB  - Vitamin A (retinol) is required for male and female reproduction as well as to
      support many developmental processes. In the male, meiotic entry of germ cells
      occurs after birth and throughout adulthood, whereas in the female, the entry
      into meiosis I occurs during embryonic development. Evidence from cultured
      embryonic ovaries suggests that the vitamin A metabolite, all-trans retinoic acid
      (atRA), initiates this process. However, in vivo evidence to support a normal
      role for atRA in meiotic entry is lacking. The present study demonstrates that
      although germ cell number is normal in ovaries from both vitamin A-sufficient
      (VAS) embryos and those that are deficient in atRA, the majority of germ cells in
      the most severely atRA-deficient group fail to enter meiosis and remain in an
      undifferentiated state. In contrast, in a group that is only moderately deficient
      in atRA, a small number of ovarian germ cells enter meiosis (30%) compared with
      75% of cells in the VAS control group. The expression of the atRA-responsive
      gene, Stra8, is reduced by approximately 90% and 50% in the severely and
      moderately atRA-deficient ovaries, respectively, compared with the VAS controls.
      These results provide the first in vivo evidence that vitamin A regulates the
      entry of germ cells into meiosis in the developing ovary.

PMID- 19587326
TI  - The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills
      in early life.
AB  - BACKGROUND: It is common to find substantial Alzheimer disease (AD) lesions,
      i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied
      brains of elderly subjects with normal cognition assessed shortly before death.
      We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic
      substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from
      the Nun Study. In addition, possible correlations between linguistic abilities in
      early life and the presence of AD pathology with and without clinical
      manifestations in late life were considered. METHODS: Design-based stereology was
      used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the
      CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n
      = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic
      ability assessed in early life was compared among all groups. RESULTS: A
      significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and
      nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI.
      Similar differences were observed with controls. Furthermore, significant higher
      idea density scores in early life were observed in controls and ASYMAD group
      compared to MCI and AD groups. CONCLUSIONS: 1) Neuronal hypertrophy may
      constitute an early cellular response to Alzheimer disease (AD) pathology or
      reflect compensatory mechanisms that prevent cognitive impairment despite
      substantial AD lesions; 2) higher idea density scores in early life are
      associated with intact cognition in late life despite the presence of AD lesions.

PMID- 19587327
TI  - Hearing improvement after bevacizumab in patients with neurofibromatosis type 2.
AB  - BACKGROUND: Profound hearing loss is a serious complication of neurofibromatosis
      type 2, a genetic condition associated with bilateral vestibular schwannomas,
      benign tumors that arise from the eighth cranial nerve. There is no medical
      treatment for such tumors. METHODS: We determined the expression pattern of
      vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2,
      neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular
      schwannomas associated with neurofibromatosis type 2 and from 22 sporadic
      schwannomas. Ten consecutive patients with neurofibromatosis type 2 and
      progressive vestibular schwannomas who were not candidates for standard treatment
      were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging
      response was defined as a decrease of at least 20% in tumor volume, as compared
      with baseline. A hearing response was defined as a significant increase in the
      word-recognition score, as compared with baseline. RESULTS: VEGF was expressed in
      100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on
      immunohistochemical analysis. Before treatment, the median annual volumetric
      growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10
      patients, tumors shrank in 9 patients, and 6 patients had an imaging response,
      which was maintained in 4 patients during 11 to 16 months of follow-up. The
      median best response to treatment was a volumetric reduction of 26%. Three
      patients were not eligible for a hearing response; of the remaining seven
      patients, four had a hearing response, two had stable hearing, and one had
      progressive hearing loss. There were 21 adverse events of grade 1 or 2.
      CONCLUSIONS: VEGF blockade with bevacizumab improved hearing in some, but not
      all, patients with neurofibromatosis type 2 and was associated with a reduction
      in the volume of most growing vestibular schwannomas.

PMID- 19587329
TI  - Organotypic cultures of prepubertal mouse testes: a method to study androgen
      action in sertoli cells while preserving their natural environment.
AB  - Cluster analysis at Postnatal Day 8-20 of putative androgen-regulated genes in
      mice with Sertoli cell-selective knockout of the androgen receptor (SCARKO) has
      pinpointed three genes (Spinlw1, Gpd1, Drd4) with an expression pattern strongly
      resembling that of Rhox5, the definitive Sertoli cell (SC) androgen-regulated
      gene. We used organotypic testis cultures from Day 8 mice to study control of
      these genes by (anti)androgens and follicle-stimulating hormone (FSH). Testis
      morphology and androgen induction of the studied genes were preserved for 48 h.
      Preincubation with ketoconazole for 24 h to block endogenous androgen production,
      followed by 24-h incubation with the synthetic androgen R1881, resulted in 45-, 5
      , 19-, and 6-fold induction of mRNA levels of Rhox5, Spinlw1, Gpd1, and Drd4,
      respectively. However, noticeable differences in control of the studied genes
      were observed. Rhox5 and Spinlw1 were fully induced by R1881 in the continuous
      (48 h) presence of ketoconazole, whereas only marginal effects were observed on
      expression of Gpd1 and Drd4. Similarly, FSH only marginally affected expression
      of Rhox5 and Spinlw1, whereas it markedly increased Gpd1 and Drd4 expression.
      Explant cultures of SCARKO testes confirmed the differential effects of FSH on
      the studied genes and, for Gpd1, showed that the effect did not depend on a
      functional androgen receptor in SC, whereas this was essential for the effects of
      FSH on Drd4. In conclusion, organotypic cultures represent the first in vitro
      approach to preserving androgen responsiveness of putative SC-expressed genes.
      This approach facilitates detailed analysis of their regulation in ways not
      possible in vivo.

PMID- 19587330
TI  - Tubulointerstitial nephritis antigen-like 1 is expressed in extraembryonic
      tissues and interacts with laminin 1 in the Reichert membrane at postimplantation
      in the mouse.
AB  - Tubulointerstitial nephritis antigen-like 1 (Tinagl1, also known as
      adrenocortical zonation factor 1 [AZ-1] or lipocalin 7) has been cloned from
      mouse adrenocortical cells and is known to be closely associated with zonal
      differentiation of adrenocortical cells. In cell culture systems, TINAGL1 is a
      matricellular protein that interacts with both structural matrix proteins and
      cell surface receptors. However, the physiological roles of TINAGL1 and
      regulation of its expression are still not clearly understood. In the present
      study, the expression and localization of TINAGL1 in peri-implantation mouse
      embryos was examined. During preimplantation, the expression of both Tinagl1 mRNA
      and TINAGL1 protein was increased just prior to implantation. In blastocysts,
      TINAGL1 expression was localized to the trophectoderm. Using a progesterone
      treated, delayed-implantation model, TINAGL1 was found to be upregulated in
      implantation-competent blastocysts after estrogen treatment. During
      postimplantation, TINAGL1 expression was restricted to extraembryonic regions.
      Marked expression was detected in the Reichert membrane on Embryonic Days 6.5
      (E6.5) and E7.5. Colocalization of laminin 1 and TINAGL1 was also examined. Using
      an anti-LAMA1 antibody, colocalization of LAMA1 and TINAGL1 was observed in
      postimplantation embryos. Colocalization was also detected in the Reichert
      membrane. Immunoprecipitation analysis determined that LAMA1 and TINAGL1 interact
      in embryos on E7.5. These results demonstrate that after implantation, TINAGL1 is
      an extraembryonic tissue-specific protein. In particular, TINAGL1 is a novel
      component of the Reichert membrane that interacts with laminin 1. These results
      suggest that TINAGL1 most likely plays a physical and physiological role in
      embryo development at postimplantation.

PMID- 19587331
TI  - Ovarian ultrasonography correlated with fecal progestins and estradiol during the
      estrous cycle and early pregnancy in giraffes (Giraffa camelopardalis
      rothschildi).
AB  - Fecal and urinary progestin analyses have shown that giraffes express a short
      reproductive cycle, averaging 15 days, compared with other large ruminants.
      However, actual ovarian events have not been correlated with the hormonal
      pattern. In this study, mature cycling female Rothschild giraffes (Giraffa
      camelopardalis rothschildi) were repeatedly examined by transrectal
      ultrasonography to correlate ovarian function with changes in fecal progestin
      (fP4 [n(c) = 6]) and estradiol (fE2 [n(c) = 6]) and serum progestin (n(c) = 2) as
      measured by enzyme immunoassay. Five females became pregnant and were monitored
      during early gestation. In this study, we discovered that hormone values for fP4
      in cycling giraffes do not correlate with the classic profile of follicular
      development, ovulation, and luteogenesis. The corpus luteum (CL) and the next
      dominant follicle were forming simultaneously. A mean +/- SD peak in fE2 of
      254.92 +/- 194.76 ng/g and subsequent ovulation occurred as early as 1 day after
      the fall in fP4. In pregnant giraffes, the CL reached a diameter significantly
      larger (mean +/- SD, 41.02 +/- 2.70 mm; P = 0.0126) than that during the cycle
      (33.48 +/- 2.80 mm), while follicular activity and fluctuating fE2 were still
      present. With this research, we demonstrated that the progesterone profile
      typically used to characterize the ovarian cycle does not correlate with luteal
      development in the ovaries of this species. Furthermore, we conclude that the
      giraffe could have evolved a short reproductive cycle because of the almost
      parallel order of ovarian events.

PMID- 19587332
TI  - Sex ratio of bovine embryos and calves originating from the left and right
      ovaries.
AB  - An asymmetric distribution of the sexes within the left and right uterine horns
      has been described in multiple species. A series of experiments were conducted to
      evaluate the sex ratio (% male) of calves gestated in the left and right uterine
      horns, as well as the sex ratio of embryos originating from the left and right
      ovaries of cattle. The sex ratio of calves gestated in the right uterine horn of
      naturally mated cows was significantly higher compared with the sex ratio of
      calves gestated in the left uterine horn. In addition, the sex ratio of the left
      and right uterine horns differed significantly from parity. The sex ratio of
      embryo transfer calves born following transfer to the left and right uterine
      horns was not significantly different. Additionally, the proportion of male
      embryos collected from the right uterine horns was significantly greater than
      from the left uterine horns of superovulated cows. The sex ratio of embryos
      collected from the left and right uterine horns of unilaterally ovariectomized
      cows was not significantly different. However, more female than male embryos were
      produced when left ovary oocytes fertilized in vitro. In conclusion, the results
      of these experiments demonstrate that a significantly greater proportion of males
      are gestated in the right uterine horn of cattle and a greater proportion of
      females in the left. Additionally, the data indicate that sex-specific selection
      pressure may be applied to embryos by ovarian factors rather than by the uterine
      environment.

PMID- 19587333
TI  - New insights into the mechanisms of fertilization: comparison of the
      fertilization steps, composition, and structure of the zona pellucida between
      horses and pigs.
AB  - The mechanism of fertilization remains largely enigmatic in mammals. Most studies
      exploring the molecular mechanism underlying fertilization have been restricted
      to a single species, generally the mouse, without a comparative approach.
      However, the identification of divergences between species could allow us to
      highlight key components in the mechanism of fertilization. In the pig, in vitro
      fertilization (IVF) and polyspermy rates are high, and spermatozoa penetrate
      easily through the zona pellucida (ZP). In contrast, IVF rates are low in the
      horse, and polyspermy is scarce. Our objective was to develop a comparative
      strategy between these two divergent models. First, we compared the role of
      equine and porcine gametes in the following five functions using intraspecific
      and interspecific IVF: ZP binding, acrosome reaction, penetration through the ZP,
      gamete fusion, and pronucleus formation. Under in vitro conditions, we showed
      that the ZP is a determining element in sperm-ZP attachment and penetration,
      whereas the capacity of the spermatozoa is of less importance. In contrast, the
      capacity of the spermatozoa is a key component of the acrosome reaction step.
      Second, we compared the composition and structure of the equine and porcine ZP.
      We observed differences in the number and localization of the ZP glycoproteins
      and in the mesh-like structure of the ZP between equine and porcine species.
      These differences might correlate with the differences in spermatozoal attachment
      and penetration rates. In conclusion, our comparative approach allows us to
      identify determining elements in the mechanism of fertilization.

PMID- 19587334
TI  - Noninvasive monitoring of reproductive activity based on fecal progestagen
      profiles and sexual behavior in Koalas, Phascolarctos cinereus.
AB  - Studies on the reproductive endocrinology of koalas have been performed mainly by
      using blood samples; however, in practice it is difficult to collect blood
      periodically because koalas are easily stressed. The purposes of the present
      study were to establish a noninvasive endocrine monitoring technique and to
      investigate the reproductive physiology of female koalas. Feces were collected
      from female northern and southern koalas, and progestagen was extracted from
      lyophilized fecal samples and determined by enzyme immunoassay. In nonpregnant
      northern and southern koalas, fecal progestagen markedly increased after
      copulation and remained high for 36.3 +/- 2.5 days and 38.9 +/- 1.4 days (luteal
      phase, mean +/- SEM), respectively. Mean (+/-SEM) progestagen levels (6.34 +/-
      0.49 microg/g) during the luteal phase in northern koalas were significantly
      higher than in southern koalas (4.19 +/- 0.24 microg/g). Fecal progestagen in
      parturient northern koalas remained high for 36.2 +/- 1.9 days (gestation period,
      34.1 +/- 0.3 days). In northern koalas, the mean levels and profiles of
      progestagen during pregnancy (6.44 +/- 0.37 microg/g) were consistent with those
      during nonpregnancy after copulation (6.34 +/- 0.49 microg/g). The duration of
      behavioral estrus in northern koalas was 13.5 +/- 0.9 days without copulation. In
      contrast, when estrous females mated, the estrous sign disappeared just after
      copulation. The mean (+/-SEM) length of the estrous cycle in northern koalas, as
      determined by behavioral estrus intervals, was 33.5 +/- 2.2 days without the
      luteal phase and 69.2 +/- 7.6 days with the luteal phase. Fecal progestagen
      analysis is a helpful and noninvasive tool to monitor ovulatory activity in
      northern and southern koalas and could help us to understand the reproductive
      activity of koalas by the combination approach with behavioral estrus.

PMID- 19587336
TI  - Images in clinical medicine. Traumatic bleb.

PMID- 19587335
TI  - The effect of linolenic Acid on bovine oocyte maturation and development.
AB  - Dietary polyunsaturated fatty acids can influence reproductive performance. In
      dairy cattle, some high-fat diets resulted in higher blastocyst rates and
      improved embryo quality. These effects may partly be mediated by a direct action
      of fatty acids on oocyte development. The present study investigated the effect
      of linolenic acid (ALA; 18:3 n-3) supplementation on bovine oocyte maturation and
      early embryo development in vitro. Treatment of cumulus-oocyte complexes (COCs)
      with 50 muM ALA significantly increased the percentage of oocytes at the
      metaphase II (MII) stage compared with untreated controls (95% +/- 2% vs. 84% +/-
      2%, respectively). Higher doses of ALA were detrimental. Treatment of COCs with
      50 muM ALA compared with controls also resulted in a significantly higher
      percentage of cleaved embryos (77% +/- 9% vs. 69% +/- 9%, respectively) and
      blastocyst rate (36% +/- 4% vs. 23% +/- 5%, respectively) and better-quality
      embryos. Furthermore, COCs treated with ALA had significant increases compared
      with controls in: 1) prostaglandin E(2) (PGE(2)) concentration (233% +/- 41%) in
      the medium, 2) intracellular cAMP at 3 h of maturation, and 3) phosphorylation of
      the mitogen-activated protein kinases (MAPKs) during the first 6 h of maturation.
      Moreover, ALA overcame the suppressive effects of the prostaglandin-endoperoxide
      synthase 2 inhibitor (NS-398) on oocyte maturation and partially improved the
      maturation rate in the presence of the MAPK kinase inhibitor (U-0126). Linolenic
      acid could not, however, recover maturation in the presence of both inhibitors.
      In conclusion, treatment of bovine COCs with ALA during oocyte maturation affects
      the molecular mechanisms controlling oocyte nuclear maturation, leading to an
      increased number of MII-stage oocytes and improved subsequent early embryo
      development. This effect is mediated both directly through MAPK pathway and
      indirectly through PGE(2) synthesis.

PMID- 19587337
TI  - Forever unprepared--the predictable unpredictability of pathogens.

PMID- 19587338
TI  - Raxibacumab for the treatment of inhalational anthrax.
AB  - BACKGROUND: Inhalational anthrax caused by Bacillus anthracis is associated with
      high mortality primarily due to toxin-mediated injury. Raxibacumab is a human
      IgG1lambda monoclonal antibody directed against protective antigen, a component
      of the anthrax toxin. METHODS: We evaluated the efficacy of raxibacumab as a
      prophylactic agent and after disease onset in a total of four randomized, placebo
      controlled studies conducted in rabbits and monkeys. Animals were exposed to an
      aerosolized target exposure of B. anthracis spores that was approximately 100
      times (in the prophylactic studies) and 200 times (in the therapeutic
      intervention studies) the median lethal dose. In the therapeutic-intervention
      studies, animals were monitored for the onset of symptoms. Animals with
      detectable protective antigen in serum, a significant increase in temperature, or
      both received a single intravenous bolus of placebo or raxibacumab at a dose of
      either 20 mg per kilogram of body weight or 40 mg per kilogram. The primary end
      point was survival at day 14 (in rabbits) or at day 28 (in monkeys). Safety
      studies were conducted with intravenous raxibacumab (40 mg per kilogram) in 333
      healthy human volunteers. RESULTS: In both rabbits and monkeys, the time to
      detection of protective antigen correlated with the time to bacteremia (r=0.9,
      P<0.001). In the therapeutic-intervention studies, the survival rate was
      significantly higher among rabbits that received raxibacumab at a dose of 40 mg
      per kilogram (44% [8 of 18]) than among rabbits that received placebo (0% [0 of
      18]; P=0.003). Raxibacumab treatment also significantly increased survival in
      monkeys (64% [9 of 14], vs. 0% [0 of 12] with placebo; P<0.001). In human
      subjects, intravenous raxibacumab at a dose of 40 mg per kilogram had a half-life
      of 20 to 22 days and provided a maximum concentration of the drug in excess of
      levels that are protective in animals. Concentrations of raxibacumab provide a
      surrogate end point that should be predictive of clinical benefit. CONCLUSIONS: A
      single dose of raxibacumab improved survival in rabbits and monkeys with
      symptomatic inhalational anthrax. (ClinicalTrials.gov number, NCT00639678.)

PMID- 19587339
TI  - Rates of serious infection after changes in regimens for medical abortion.
AB  - BACKGROUND: From 2001 through March 2006, Planned Parenthood health centers
      throughout the United States provided medical abortion (abortion by means of
      medication) principally by a regimen of oral mifepristone followed 24 to 48 hours
      later by vaginal misoprostol. In response to concern about serious infections, in
      early 2006 Planned Parenthood changed the route of misoprostol administration
      from vaginal to buccal and required either routine provision of antibiotics or
      universal screening and treatment for chlamydia; in July 2007, Planned Parenthood
      began requiring routine treatment with antibiotics for all medical abortions.
      METHODS: We performed a retrospective analysis assessing the rates of serious
      infection after medical abortion during a time when misoprostol was administered
      vaginally (through March 2006), as compared with rates after a change to buccal
      administration of misoprostol and after initiation of additional infection
      reduction measures. RESULTS: Rates of serious infection dropped significantly
      after the joint change to buccal misoprostol from vaginal misoprostol and to
      either testing for sexually transmitted infection or routine provision of
      antibiotics as part of the medical abortion regimen. The rate declined 73%, from
      0.93 per 1000 abortions to 0.25 per 1000 (absolute reduction, 0.67 per 1000; 95%
      confidence interval [CI], 0.44 to 0.94; P<0.001). The subsequent change to
      routine provision of antibiotics led to a further significant reduction in the
      rate of serious infection - a 76% decline, from 0.25 per 1000 abortions to 0.06
      per 1000 (absolute reduction, 0.19 per 1000; 95% CI, 0.02 to 0.34; P=0.03).
      CONCLUSIONS: The rate of serious infection after medical abortion declined by 93%
      after a change from vaginal to buccal administration of misoprostol combined with
      routine administration of antibiotics.

PMID- 19587340
TI  - Lack of association between folate-receptor autoantibodies and neural-tube
      defects.
AB  - BACKGROUND: A previous report described the presence of autoantibodies against
      folate receptors in 75% of serum samples from women with a history of pregnancy
      complicated by a neural-tube defect, as compared with 10% of controls. We sought
      to confirm this finding in an Irish population, which traditionally has had a
      high prevalence of neural-tube defects. METHODS: We performed two studies. Study
      1 consisted of analysis of stored frozen blood samples collected from 1993
      through 1994 from 103 mothers with a history of pregnancy complicated by a neural
      tube defect (case mothers), 103 mothers with a history of pregnancy but no
      complication by a neural-tube defect (matched with regard to number of
      pregnancies and sampling dates), 58 women who had never been pregnant, and 36
      men. Study 2, conducted to confirm that the storage of samples did not influence
      the folate-receptor autoantibodies, included fresh samples from 37 case mothers,
      22 control mothers, 10 women who had never been pregnant, and 9 men. All samples
      were assayed for blocking and binding autoantibodies against folate receptors.
      RESULTS: In Study 1, blocking autoantibodies were found in 17% of case mothers,
      as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence
      interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with
      32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed
      similar results, indicating that sample degradation was unlikely. CONCLUSIONS:
      The presence and titer of maternal folate-receptor autoantibodies were not
      significantly associated with a neural-tube defect-affected pregnancy in this
      Irish population.

PMID- 19587341
TI  - Investigation of the cause of death in a gene-therapy trial.
AB  - We present a case of disseminated histoplasmosis, complicated by retroperitoneal
      bleeding and leading to death, in a patient who was receiving systemic
      immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene
      therapy trial. This trial was designed to evaluate intraarticular delivery of a
      tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated
      virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's
      receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy
      while she was living in an area where histoplasmosis was endemic was thought to
      be the most likely explanation for the infection; the evidence presented suggests
      that this fatal infection was unlikely to have been related to exposure to the
      agent administered in the gene-therapy trial. This case reinforces the importance
      of considering infectious complications, such as those from endemic mycoses, in
      patients receiving treatment with a TNF-alpha antagonist and the importance of
      having a well-designed monitoring plan when subjects in a research study become
      ill. (ClinicalTrials.gov number, NCT00126724.)

PMID- 19587342
TI  - Clinical practice. Screening for ovarian cancer.

PMID- 19587343
TI  - Images in clinical medicine. Cutaneous anthrax.

PMID- 19587344
TI  - Case records of the Massachusetts General Hospital. Case 21-2009. A 61-year-old
      woman with abdominal pain, weight loss, and renal failure.

PMID- 19587345
TI  - Protecting against future shock--inhalational anthrax.

PMID- 19587346
TI  - Gene therapy--still a work in clinical and regulatory progress.

PMID- 19587347
TI  - Protecting privacy and the public--limits on police use of bioidentifiers in
      Europe.

PMID- 19587348
TI  - Prostate-cancer screening.

PMID- 19587349
TI  - Esomeprazole for asthma.

PMID- 19587350
TI  - Long-acting beta-agonists in asthma.

PMID- 19587351
TI  - Prescribing records and the First Amendment.

PMID- 19587352
TI  - Anti-CTLA4 antibody-induced lupus nephritis.

PMID- 19587353
TI  - Genetics of type 1A diabetes.

PMID- 19587354
TI  - Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and
      ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive
      K(+) channel.
AB  - OBJECTIVE: In the pancreatic beta-cell, ATP-sensitive K(+) (K(ATP)) channels
      couple metabolism with excitability and consist of Kir6.2 and SUR1 subunits
      encoded by KCNJ11 and ABCC8, respectively. Sulfonylureas, which inhibit the
      K(ATP) channel, are used to treat type 2 diabetes. Rare activating mutations
      cause neonatal diabetes, whereas the common variants, E23K in KCNJ11 and S1369A
      in ABCC8, are in strong linkage disequilibrium, constituting a haplotype that
      predisposes to type 2 diabetes. To date it has not been possible to establish
      which of these represents the etiological variant, and functional studies are
      inconsistent. Furthermore, there have been no studies of the S1369A variant or
      the combined effect of the two on K(ATP) channel function. RESEARCH DESIGN AND
      METHODS: The patch-clamp technique was used to study the nucleotide sensitivity
      and sulfonylurea inhibition of recombinant human K(ATP) channels containing
      either the K23/A1369 or E23/S1369 variants. RESULTS: ATP sensitivity of the
      K(ATP) channel was decreased in the K23/A1369 variant (half-maximal inhibitory
      concentration [IC(50)] = 8.0 vs. 2.5 mumol/l for the E23/S1369 variant), although
      there was no difference in ADP sensitivity. The K23/A1369 variant also displayed
      increased inhibition by gliclazide, an A-site sulfonylurea drug (IC(50) = 52.7
      vs. 188.7 nmol/l for the E23/S1369 variant), but not by glibenclamide (AB site)
      or repaglinide (B site). CONCLUSIONS: Our findings indicate that the common
      K23/A1369 variant K(ATP) channel displays decreased ATP inhibition that may
      contribute to the observed increased risk for type 2 diabetes. Moreover, the
      increased sensitivity of the K23/A1369 variant to the A-site sulfonylurea drug
      gliclazide may provide a pharmacogenomic therapeutic approach for patients with
      type 2 diabetes who are homozygous for both risk alleles.

PMID- 19587355
TI  - Selective inhibition of protein kinase C beta(2) attenuates inducible nitric
      oxide synthase-mediated cardiovascular abnormalities in streptozotocin-induced
      diabetic rats.
AB  - OBJECTIVE: Impaired cardiovascular function in diabetes is partially attributed
      to pathological overexpression of inducible nitric oxide synthase (iNOS) in
      cardiovascular tissues. We examined whether the hyperglycemia-induced increased
      expression of iNOS is protein kinase C-beta(2) (PKCbeta(2)) dependent and whether
      selective inhibition of PKCbeta reduces iNOS expression and corrects abnormal
      hemodynamic function in streptozotocin (STZ)-induced diabetic rats. RESEARCH
      DESIGN AND METHODS: Cardiomyocytes and aortic vascular smooth muscle cells (VSMC)
      from nondiabetic rats were cultured in low (5.5 mmol/l) or high (25 mmol/l)
      glucose or mannitol (19.5 mmol/l mannitol + 5.5 mmol/l glucose) conditions in the
      presence of a selective PKCbeta inhibitor, LY333531 (20 nmol/l). Further, the in
      vivo effects of PKCbeta inhibition on iNOS-mediated cardiovascular abnormalities
      were tested in STZ-induced diabetic rats. RESULTS: Exposure of cardiomyocytes to
      high glucose activated PKCbeta(2) and increased iNOS expression that was
      prevented by LY333531. Similarly, treatment of VSMC with LY333531 prevented high
      glucose-induced activation of nuclear factor kappaB, extracellular signal-related
      kinase, and iNOS overexpression. Suppression of PKCbeta(2) expression by small
      interference RNA decreased high-glucose-induced nuclear factor kappaB and
      extracellular signal-related kinase activation and iNOS expression in VSMC.
      Administration of LY333531 (1 mg/kg/day) decreased iNOS expression and formation
      of peroxynitrite in the heart and superior mesenteric arteries and corrected the
      cardiovascular abnormalities in STZ-induced diabetic rats, an action that was
      also observed with a selective iNOS inhibitor, L-NIL. CONCLUSIONS: Collectively,
      these results suggest that inhibition of PKCbeta(2) may be a useful approach for
      correcting abnormal hemodynamics in diabetes by preventing iNOS mediated
      nitrosative stress.

PMID- 19587356
TI  - Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system
      on nephrin expression in streptozotocin-treated mice and human cultured
      podocytes.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the
      CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been
      implicated in the pathogenesis of diabetic nephropathy. To assess the potential
      relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria,
      we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin
      expression in cultured podocytes. Moreover, we investigated in vivo if glomerular
      CCR2 expression is altered in kidney biopsies from patients with diabetic
      nephropathy and whether lack of MCP-1 affects proteinuria and expression of
      nephrin in experimental diabetes. RESEARCH DESIGN AND METHODS: Expression of
      nephrin was assessed in human podocytes exposed to rh-MCP-1 by immunofluorescence
      and real-time PCR. Glomerular CCR2 expression was studied in 10 kidney sections
      from patients with overt nephropathy and eight control subjects by
      immunohistochemistry. Both wild-type and MCP-1 knockout mice were made diabetic
      with streptozotocin. Ten weeks after the onset of diabetes, albuminuria and
      expression of nephrin, synaptopodin, and zonula occludens-1 were examined by
      immunofluorescence and immunoblotting. RESULTS: In human podocytes, MCP-1 binding
      to the CCR2 receptor induced a significant reduction in nephrin both mRNA and
      protein expression via a Rho-dependent mechanism. The MCP-1 receptor, CCR2, was
      overexpressed in the glomerular podocytes of patients with overt nephropathy. In
      experimental diabetes, MCP-1 was overexpressed within the glomeruli and the
      absence of MCP-1 reduced both albuminuria and downregulation of nephrin and
      synaptopodin. CONCLUSIONS: These findings suggest that the MCP-1/CCR2 system may
      be relevant in the pathogenesis of proteinuria in diabetes.

PMID- 19587357
TI  - A systematic meta-analysis of genetic association studies for diabetic
      retinopathy.
AB  - OBJECTIVE: Diabetic retinopathy is a sight-threatening microvascular complication
      of diabetes with a complex multifactorial pathogenesis. A systematic meta
      analysis was undertaken to collectively assess genetic studies and determine
      which previously investigated polymorphisms are associated with diabetic
      retinopathy. RESEARCH DESIGN AND METHODS: All studies investigating the
      association of genetic variants with the development of diabetic retinopathy were
      identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95%
      CIs were calculated for single nucleotide polymorphisms and microsatellite
      markers previously investigated in at least two published studies. RESULTS:
      Twenty genes and 34 variants have previously been studied in multiple cohorts.
      The aldose reductase (AKR1B1) gene was found to have the largest number of
      polymorphisms significantly associated with diabetic retinopathy. The z-2
      microsatellite was found to confer risk (OR 2.33 [95% CI 1.49-3.64], P = 2 x 10(
      4)) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36-0.93],
      P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of
      ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also
      significantly protective against diabetic retinopathy in type 1 diabetes (0.5
      [0.35-0.71], P = 1.00 x 10(-4)), regardless of ethnicity. These associations were
      also found in the white population alone (P < 0.05). Polymorphisms in NOS3, VEGF,
      ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta
      analysis. CONCLUSIONS: Variations within the AKR1B1 gene are highly significantly
      associated with diabetic retinopathy development irrespective of ethnicity.
      Identification of genetic risk factors in diabetic retinopathy will assist in
      further understanding of this complex and debilitating diabetes complication.

PMID- 19587358
TI  - Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled
      estrogen receptor in pancreatic islet survival.
AB  - OBJECTIVE: We showed that 17beta-estradiol (E(2)) favors pancreatic beta-cell
      survival via the estrogen receptor-alpha (ERalpha) in mice. E(2) activates
      nuclear estrogen receptors via an estrogen response element (ERE). E(2) also
      activates nongenomic signals via an extranuclear form of ERalpha and the G
      protein-coupled estrogen receptor (GPER). We studied the contribution of estrogen
      receptors to islet survival. RESEARCH DESIGN AND METHODS: We used mice and islets
      deficient in estrogen receptor-alpha (alphaERKO(-/-)), estrogen receptor-beta
      (betaERKO(-/-)), estrogen receptor-alpha and estrogen receptor-beta
      (alphabetaERKO(-/-)), and GPER (GPERKO(-/-)); a mouse lacking ERalpha binding to
      the ERE; and human islets. These mice and islets were studied in combination with
      receptor-specific pharmacological probes. RESULTS: We show that ERalpha
      protection of islet survival is ERE independent and that E(2) favors islet
      survival through extranuclear and membrane estrogen receptor signaling. We show
      that ERbeta plays a minor cytoprotective role compared to ERalpha. Accordingly,
      betaERKO(-/-) mice are mildly predisposed to streptozotocin-induced islet
      apoptosis. However, combined elimination of ERalpha and ERbeta in mice does not
      synergize to provoke islet apoptosis. In alphabetaERKO(-/-) mice and their
      islets, E(2) partially prevents apoptosis suggesting that an alternative pathway
      compensates for ERalpha/ERbeta deficiency. We find that E(2) protection of islet
      survival is reproduced by a membrane-impermeant E(2) formulation and a selective
      GPER agonist. Accordingly, GPERKO(-/-) mice are susceptible to streptozotocin
      induced insulin deficiency. CONCLUSIONS: E(2) protects beta-cell survival through
      ERalpha and ERbeta via ERE-independent, extra-nuclear mechanisms, as well as GPER
      dependent mechanisms. The present study adds a novel dimension to estrogen
      biology in beta-cells and identifies GPER as a target to protect islet survival.

PMID- 19587359
TI  - Regulation and function of FTO mRNA expression in human skeletal muscle and
      subcutaneous adipose tissue.
AB  - OBJECTIVE: Common variants in FTO (the fat mass- and obesity-associated gene)
      associate with obesity and type 2 diabetes. The regulation and biological
      function of FTO mRNA expression in target tissue is unknown. We investigated the
      genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose
      tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN
      AND METHODS: The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1)
      298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to
      type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years)
      nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including
      indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose
      tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS: Heritability of
      FTO expression in both tissues was low, and FTO expression was not influenced by
      FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by
      age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA
      expression. FTO mRNA expression in adipose tissue was associated with an
      atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively
      associated to fat and positively to glucose oxidation rates as well as positively
      correlated with expression of genes involved in oxidative phosphorylation
      including PGC1alpha. CONCLUSIONS: The heritability of FTO expression in adipose
      tissue and skeletal muscle is low and not influenced by obesity-associated FTO
      genotype. The age-dependent decline in FTO expression is associated with
      peripheral defects of glucose and fat metabolism.

PMID- 19587361
TI  - Long-term fish intake is associated with less severe depressive symptoms among
      elderly men and women: the MEDIS (MEDiterranean ISlands Elderly) epidemiological
      study.
AB  - Objectives. This work aims at exploring the association between fish intake and
      depressive symptoms, in older adults. Method. During 2005-2007, 1,190 men and
      women (>65 years) free living in various Greek islands and in Cyprus participated
      in the study. Depressive symptoms were assessed using the validated Geriatric
      Depression Scale (GDS), and foods intake through a Food Frequency Questionnaire.
      Results. Almost 70% of the participants scored above the depressive cutoff (i.e.,
      GDS score > 5), with women having higher values. People classified under the 1st
      tertile of GDS score (i.e., GDS </= 5) were more educated, physically active, and
      report higher fish consumption. One portion increase of fish consumption per week
      was associated with 0.58 times (95% confidence interval: 0.45-0.73) lower
      likelihood of having GDS score above the clinical threshold, after various
      adjustments were made. Discussion. These findings may assist public health policy
      makers in better preventing emotional disorders among the elderly by promoting
      healthier eating habits.

PMID- 19587360
TI  - Vasohibin-1, a negative feedback regulator of angiogenesis, ameliorates renal
      alterations in a mouse model of diabetic nephropathy.
AB  - OBJECTIVE: The involvement of proangiogenic factors such as vascular endothelial
      growth factor as well as the therapeutic efficacy of angiogenesis inhibitors in
      early diabetic nephropathy has been reported. Vasohibin-1 (VASH-1) is a unique
      endogenous angiogenesis inhibitor that is induced in endothelial cells by
      proangiogenic factors. We investigated the therapeutic efficacy of VASH-1 in an
      early diabetic nephropathy model. RESEARCH DESIGN AND METHODS: Streptozotocin-
      induced type 1 diabetic mice received intravenous injections of adenoviral
      vectors encoding VASH-1 (AdhVASH-1) or beta-gal (AdLacZ) every other week and
      were killed after 28 days. RESULTS: Treatment with AdhVASH-1 resulted in
      sustained increase in the protein levels of VASH-1 in the liver and sera, in the
      absence of any inflammatory alterations. AdhVASH-1 treatment significantly
      suppressed renal hypertrophy, glomerular hypertrophy, glomerular hyperfiltration,
      albuminuria, increase of the CD31(+) glomerular endothelial area, F4/80(+)
      monocyte/macrophage infiltration, the accumulation of type IV collagen, and
      mesangial matrix compared with AdLacZ-treated diabetic mice. Increase in the
      renal levels of transforming growth factor-beta1, monocyte chemoattractant
      protein-1, and receptor for advanced glycation end products in diabetic animals
      was significantly suppressed by AdhVASH-1 (real-time PCR and immunoblot). VASH-1
      significantly suppressed the increase of transforming growth factor-beta,
      monocyte chemoattractant protein-1, and receptor for advanced glycation end
      products, induced by high ambient glucose in cultured mouse mesangial cells.
      Increased phosphorylation of VEGFR2 was suppressed in AdVASH-1-treated diabetic
      animals and in cultured glomerular endothelial cells. Endogenous mouse VASH-1 was
      localized to the mesangial and endothelial area in glomeruli of diabetic mice.
      CONCLUSIONS: These results suggest the potential therapeutic efficacy of VASH-1
      in treating early diabetic nephropathy potentially mediated via glomerular
      endothelial and mesangial cells.

PMID- 19587362
TI  - Renal effects of aliskiren compared with and in combination with irbesartan in
      patients with type 2 diabetes, hypertension, and albuminuria.
AB  - OBJECTIVE: We investigated whether the antiproteinuric effect of the direct renin
      inhibitor aliskiren is comparable to that of irbesartan and the effect of the
      combination. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized,
      crossover trial. After a 1-month washout period, 26 patients with type 2
      diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to
      four 2-month treatment periods in random order with placebo, 300 mg aliskiren
      once daily, 300 mg irbesartan once daily, or the combination using identical
      doses. Patients received furosemide in a stable dose throughout the study. The
      primary end point was a change in albuminuria. Secondary measures included change
      in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS: Placebo
      geometric mean albuminuria was 258 mg/day (range 84-2,361), mean +/- SD 24-h
      blood pressure was 140/73 +/- 15/8 mmHg, and GFR was 89 +/- 27 ml/min per 1.73
      m(2). Aliskiren treatment reduced albuminuria by 48% (95% CI 27-62) compared with
      placebo (P < 0.001), not significantly different from the 58% (42-79) reduction
      with irbesartan treatment (P < 0.001 vs. placebo). Combination treatment reduced
      albuminuria by 71% (59-79), more than either monotherapy (P < 0.001 and P =
      0.028). Fractional clearances of albumin were significantly reduced (46, 56, and
      67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg
      by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P < 0.001/P = 0.002), and
      10/6 mmHg by the combination (P = 0.001/P < 0.001). GFR was significantly reduced
      4.6 (95% CI 0.3-8.8) ml/min per 1.73 m(2) by aliskiren, 8.0 (3.6-12.3) ml/min per
      1.73 m(2) by irbesartan, and 11.7 (7.4-15.9) ml/min per 1.73 m(2) by the
      combination. CONCLUSIONS: The combination of aliskiren and irbesartan is more
      antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.

PMID- 19587363
TI  - Short-term dynamics and metabolic impact of abdominal fat depots after bariatric
      surgery.
AB  - OBJECTIVE: Bariatric surgery is gaining acceptance as an efficient treatment
      modality for obese patients. Mechanistic explanations regarding the effects of
      bariatric surgery on body composition and fat distribution are still limited.
      RESEARCH DESIGN AND METHODS: Intra-abdominal and subcutaneous fat depots were
      evaluated using computed tomography in 27 obese patients prior to and 6 months
      following bariatric surgery. Associations with anthropometric and clinical
      changes were evaluated. RESULTS: Excess weight loss 6 months following surgery
      was 47% in male and 42.6% in female subjects. Visceral fat and subcutaneous fat
      were reduced by 35% and 32%, respectively, in both sexes, thus the visceral-to
      subcutaneous fat ratio remained stable. The strongest relation between absolute
      and relative changes in visceral and subcutaneous fat was demonstrated for the
      excess weight loss following the operations (r approximately 0.6-0.7), and these
      relations were strengthened further following adjustments for sex, baseline BMI,
      and fat mass. Changes in waist circumference and fat mass had no relation to
      changes in abdominal fat depots. All participants met the criteria of the
      metabolic syndrome at baseline, and 18 lost the diagnosis on follow-up. A lower
      baseline visceral-to-subcutaneous fat ratio (0.43 +/- 0.15 vs. 0.61 +/- 0.21, P =
      0.02) was associated with clinical resolution of metabolic syndrome parameters.
      CONCLUSIONS: The ratio between visceral and subcutaneous abdominal fat remains
      fairly constant 6 months following bariatric procedures regardless of sex,
      procedure performed, or presence of metabolic complications. A lower baseline
      visceral-to-abdominal fat ratio is associated with improvement in metabolic
      parameters.

PMID- 19587364
TI  - Regression from pre-diabetes to normal glucose regulation in the diabetes
      prevention program.
AB  - OBJECTIVE: Participants in the Diabetes Prevention Program (DPP) randomized to
      intensive lifestyle modification (ILS) or metformin had a significantly reduced
      incidence of diabetes compared with those randomized to placebo, yet most were
      still at risk because they had pre-diabetes. We explored the effect of baseline
      characteristics, weight change, ILS, and metformin on regression from pre
      diabetes to the lowest-risk state of normal glucose regulation (NGR) defined by
      American Diabetes Association criteria. RESEARCH DESIGN AND METHODS: The DPP was
      a prospective randomized trial. Cox proportional hazards modeling was used to
      identify predictors of regression from pre-diabetes to NGR over 3 years of follow
      up. RESULTS: Lower baseline fasting (hazard ratio 1.52, P < 0.01) and 2-h (1.24,
      P < 0.01) glucose predicted regression to NGR, as did younger age (1.07, P <
      0.01) and greater insulin secretion (1.09, P = 0.04). ILS (2.05, P < 0.01) and
      weight loss (1.34, P < 0.01) had significant and independent effects on
      regression. A nonsignificant trend for regression was also observed for metformin
      (1.25, P = 0.06), male sex (1.17, P = 0.08), and insulin sensitivity (1.07, P =
      0.09). In those entering the study with both impaired fasting glucose (IFG) and
      impaired glucose tolerance (IGT), male sex and insulin sensitivity predicted
      regression to isolated IFG, whereas ILS, metformin, female sex, and greater
      insulin secretion predicted regression to isolated IGT. CONCLUSIONS: Insulin
      secretion, and other biologic processes retained with younger age, are key in
      restoring NGR in people with pre-diabetes. However, NGR may also be attained
      through weight loss and additional aspects of ILS.

PMID- 19587365
TI  - Preservation of beta-cell function in autoantibody-positive youth with diabetes.
AB  - OBJECTIVE: To determine the extent of beta-cell function in youth with diabetes
      and GAD65 and/or IA2 autoantibodies. RESEARCH DESIGN AND METHODS: Fasting C
      peptide levels from 2,789 GAD65- and/or IA2 autoantibody-positive youth aged 1-23
      years from the SEARCH for Diabetes in Youth study were used. Preserved beta-cell
      function was defined on the basis of cut points derived from the Diabetes Control
      and Complications Trial (DCCT) (fasting C-peptide > or =0.23 ng/ml) and from the
      U.S. adolescent population of the National Health and Nutrition Examination
      Survey (NHANES) 5th percentile for fasting C-peptide (> or =1.0 ng/ml). We
      compared the clinical characteristics between those with and without preserved
      beta-cell function. RESULTS: Within the first year of diagnosis, 82.9% of youth
      had a fasting C-peptide > or =0.23 ng/ml and 31.2% had values > or =1.0 ng/ml.
      Among those with > or =5 years of diabetes duration, 10.7% had preserved beta
      cell function based on the DCCT cutoff and 1.0% were above the 5th percentile of
      the NHANES population. CONCLUSIONS: Within the 1st year of diagnosis, four of
      five youth with autoantibody-positive diabetes have clinically significant
      amounts of residual beta-cell function and about one-third have fasting C-peptide
      levels above the 5th percentile of a healthy adolescent population. Even 5 years
      after diagnosis, 1 of 10 has fasting C-peptide above a clinically significant
      threshold. These findings have implications for clinical classification of youth
      with diabetes as well as clinical trials aimed to preserve beta-cell function
      after diabetes onset.

PMID- 19587366
TI  - Large-fiber dysfunction in diabetic peripheral neuropathy is predicted by
      cardiovascular risk factors.
AB  - OBJECTIVE: Diabetic large-nerve fiber dysfunction, as measured by vibration
      perception threshold (VPT), predicts foot ulceration, amputation, and mortality.
      Thus, determination of modifiable risk factors is of great clinical importance.
      RESEARCH DESIGN AND METHODS: We assessed 1,407 patients with type 1 diabetes and
      a normal VPT participating in the EURODIAB Prospective Complications Study, at
      baseline mean +/- SD age of 32.7 +/- 10.2 years with diabetes duration of 14.7 +/
      9.3 years and follow-up of 7.3 +/- 0.6 years. VPT was measured using
      biothesiometry on the right big toe and medial malleolus. An abnormal result was
      defined as >2 SD from the predicted mean for the patient s age. RESULTS: An
      abnormal VPT was associated with an increased incidence of gangrene, amputation,
      foot ulceration, leg bypass or angioplasty, and mortality (P < OR = 0.02). The
      incidence of abnormal VPT was 24% over the 7.3-year follow-up. Duration of
      diabetes and A1C significantly influenced the incidence of abnormal VPT (P <
      0.0001). After correction for these, established risk factors for cardiovascular
      disease (CVD), including male sex (P = 0.0004), hypertension (P < 0.0001), total
      cholesterol (P = 0.002), LDL cholesterol (P = 0.01), smoking (P < 0.0001), weight
      (P < 0.0001), and diabetes complications (retinopathy [P = 0.0001], nephropathy
      [P = 0.01], and autonomic neuropathy [P = 0.001]), were all found to be
      significant risk factors. A previous history of CVD doubled the incidence of
      abnormal VPT. CONCLUSIONS: This prospective study indicates that cardiovascular
      risk factors predict development of large-fiber dysfunction, which may account
      for the high mortality rate in patients with an abnormal VPT, and emphasizes the
      importance of early determination of VPT to detect subclinical neuropathy and to
      address cardiovascular risk factors.

PMID- 19587368
TI  - Abdominal adiposity is associated with elevated C-reactive protein independent of
      BMI in healthy nonobese people.
AB  - OBJECTIVE: There is debate over the most appropriate adiposity markers of obesity
      associated health risks. We evaluated the relationship between fat distribution
      and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity.
      RESEARCH DESIGN AND METHODS: We studied 350 people with abdominal adiposity
      (waist-to-hip ratio [WHR] > or =0.9 in male and > or =0.85 in female subjects)
      and 199 control subjects (WHR <0.9 in male and <0.85 in female subjects) matched
      for BMI and age. We measured hs-CRP and major cardiovascular risk factors.
      RESULTS: Participants with abdominal adiposity had BMI similar to that in control
      subjects (24.8 +/- 2.5 vs. 24.7 +/- 2.2 kg/m(2), respectively), but significantly
      higher waist circumference (96.4 +/- 6.0 vs. 83.3 +/- 6.7 cm; P < 0.01) and WHR
      (1.07 +/- 0.08 vs. 0.85 +/- 0.05; P < 0.001). Compared with the control subjects,
      participants with abdominal adiposity had an adverse cardiovascular risk factor
      profile, significantly higher hs-CRP (1.96 +/- 2.60 vs. 1.53 +/- 1.74 mg/dl; P <
      0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl). CONCLUSIONS:
      In nonobese people, moderate abdominal adiposity is associated with markers of
      subclinical inflammation independent of BMI.

PMID- 19587367
TI  - Cystatin C, albuminuria, and mortality among older adults with diabetes.
AB  - OBJECTIVE: Albuminuria and impaired glomerular filtration rate (GFR) are each
      associated with poor health outcomes among individuals with diabetes. Joint
      associations of albuminuria and impaired GFR with mortality have not been
      comprehensively evaluated in this population. RESEARCH DESIGN AND METHODS: This
      is a cohort study among Cardiovascular Health Study participants with diabetes,
      mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine.
      Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.
      RESULTS: Of 691 participants, 378 died over 10 years of follow-up. Cystatin C
      estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min
      per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased
      mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97),
      and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes
      duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol,
      lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent
      heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of
      mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than
      creatinine-based estimated GFR. CONCLUSIONS: Albuminuria and impaired GFR were
      independent, additive risk factors for mortality among older adults with
      diabetes. These findings support current recommendations to regularly assess both
      albuminuria and GFR in the clinical care of patients with diabetes; a focus on
      interventions to prevent or treat CVD in the presence of albuminuria, impaired
      GFR, or both; and further consideration of cystatin C use in clinical care.

PMID- 19587369
TI  - Changes in insulin secretion and insulin sensitivity in relation to the glycemic
      outcomes in subjects with impaired glucose tolerance in the Indian Diabetes
      Prevention Programme-1 (IDPP-1).
AB  - OBJECTIVE: The Indian Diabetes Prevention Programme-1 (IDPP-1) showed that
      lifestyle modification (LSM) and metformin were effective for primary prevention
      of diabetes in subjects with impaired glucose tolerance (IGT). Among subjects
      followed up for 3 years (n = 502), risk reductions versus those for the control
      group were 28.5, 26.4, and 28.2% in LSM, metformin (MET), and LSM plus MET
      groups, respectively. In this analysis, the roles of changes in secretion and
      action of insulin in improving the outcome were studied. RESEARCH DESIGN AND
      METHODS: For this analysis, 437 subjects (93 subjects with normoglycemia [NGT],
      150 subjects with IGT, and 194 subjects with diabetes) were included.
      Measurements of anthropometry, plasma glucose, and plasma insulin at baseline and
      at follow-up were available for all of them. Indexes of insulin resistance
      (homeostasis model assessment of insulin resistance) and beta-cell function
      (insulinogenic index [DeltaI/G]: 30-min fasting insulin divided by 30-min
      glucose) were also analyzed in relation to the outcome. RESULTS: Subjects with
      IGT showed a deterioration in beta-cell function with time. Individuals with
      higher insulin resistance and/or low beta-cell function at baseline had poor
      outcome on follow-up. In relation to no abnormalities, the highest incidence of
      diabetes occurred when both abnormalities coexisted (54.9 vs. 33.7%, chi(2) =
      7.53, P = 0.006). Individuals having abnormal insulin resistance (41.1%) or
      abnormal DeltaI/G (51.2%, chi(2) = 4.87, P = 0.027 vs. no abnormalities) had
      lower incidence. Normal beta-cell function with improved insulin sensitivity
      facilitated reversal to NGT, whereas deterioration in both resulted in diabetes.
      The beneficial changes were better with intervention than in the control group.
      Intervention groups had higher rates of NGT and lower rates of diabetes.
      CONCLUSIONS: In the IDPP-1 subjects, beneficial outcomes occurred because of
      improved insulin action and sensitivity caused by the intervention strategies.

PMID- 19587370
TI  - Impaired awareness of hypoglycemia in a population-based sample of children and
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: To determine the prevalence and clinical associations of impaired
      awareness of hypoglycemia in a population-based sample of children and
      adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: A validated
      questionnaire was administered to 656 patients with type 1 diabetes over a 6
      month period to determine hypoglycemia awareness status. Case ascertainment was
      79% of the clinic population. The rate of severe hypoglycemia was determined by
      data collected prospectively in the preceding year. RESULTS: Impaired awareness
      of hypoglycemia was present in 29% of patients. Patients with impaired awareness
      of hypoglycemia had an earlier onset of diabetes (P < 0.001), were younger (P <
      0.001), and had lower mean levels of A1C since diabetes onset (P = 0.006) and at
      their last visit (P = 0.001). The overall rate of severe hypoglycemia was 24.5
      episodes per 100 patient-years in the preceding year. The severe hypoglycemia
      rate was higher in those with impaired awareness of hypoglycemia (37.1 vs. 19.3
      episodes per 100 patient-years, P < 0.001). Among patients aged <6 years (n =
      46), 59% of care providers reported impaired awareness of hypoglycemia, and the
      rate of severe hypoglycemia was significantly higher in those reporting impaired
      awareness (33.3 vs. 52 episodes per 100 patient-years, P = 0.02). More patients
      with recurrent hypoglycemia reported impaired awareness of hypoglycemia (47 vs.
      28%, P = 0.03). CONCLUSIONS: A significant proportion of children and adolescents
      with type 1 diabetes have impaired awareness of hypoglycemia. Screening for
      impaired awareness is an important component of routine diabetes care and can
      identify patients at increased risk of a severe hypoglycemic event.

PMID- 19587371
TI  - Wound chronicity, inpatient care, and chronic kidney disease predispose to MRSA
      infection in diabetic foot ulcers.
AB  - OBJECTIVE: To determine the microbiological profile of diabetes-related foot
      infections (DRFIs) and the impact of wound duration, inpatient treatment, and
      chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: Postdebridement
      microbiological samples were collected from individuals presenting with DRFIs
      from 1 January 2005 to 31 December 2007. RESULTS: A total of 653 specimens were
      collected from 379 individuals with 36% identifying only one isolate. Of the
      total isolates, 77% were gram-positive bacteria (staphylococci 43%, streptococci
      13%). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 23%;
      risk factors for MRSA included prolonged wound duration (odds ratio 2.31),
      inpatient management (2.19), and CKD (OR 1.49). Gram-negative infections were
      more prevalent with inpatient management (P = 0.002) and prolonged wound duration
      (P < 0.001). Pseudomonal isolates were more common in chronic wounds (P < 0.001).
      CONCLUSIONS: DRFIs are predominantly due to gram-positive aerobes but are usually
      polymicrobial and increase in complexity with inpatient care and ulcer duration.
      In the presence of prolonged duration, inpatient management, or CKD, empiric MRSA
      antibiotic cover should be considered.

PMID- 19587372
TI  - Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule
      secretion.
AB  - Protein kinase C-delta (PKC-delta) is expressed in platelets and activated
      downstream of protease-activated receptors (PARs) and glycoprotein VI (GPVI)
      receptors. We have previously shown that PKC-delta positively regulates PAR
      mediated dense granule secretion, whereas it negatively regulates GPVI-mediated
      dense granule secretion. We further investigated the mechanism of such
      differential regulation of dense granule release by PKC-delta in platelets. SH2
      domain-containing inositol phosphatase-1 (SHIP-1) is phosphorylated on Y1020, a
      marker for its activation, upon stimulation of human platelets with PAR agonists
      SFLLRN and AYPGKF or GPVI agonist convulxin. GPVI-mediated SHIP-1 phosphorylation
      occurred rapidly at 15 seconds, whereas PAR-mediated phosphorylation was delayed,
      occurring at 1 minute. Lyn and SHIP-1, but not SHIP-2 or Shc, preferentially
      associated with PKC-delta on stimulation of platelets with a GPVI agonist, but
      not with a PAR agonist. In PKC-delta-null murine platelets, convulxin-induced
      SHIP-1 phosphorylation was inhibited. Furthermore, in Lyn null murine platelets,
      GPVI-mediated phosphorylations on Y-1020 of SHIP-1 and Y311 of PKC-delta were
      inhibited. In murine platelets lacking Lyn or SHIP-1, GPVI-mediated dense granule
      secretions are potentiated, whereas PAR-mediated dense granule secretions are
      inhibited. Therefore, we conclude that Lyn-mediated phosphorylations of PKC-delta
      and SHIP-1 and their associations negatively regulate GPVI-mediated dense granule
      secretion in platelets.

PMID- 19587374
TI  - How I treat the antiphospholipid syndrome.
AB  - This article discusses how we approach medical decision making in the treatment
      of the various facets of the antiphospholipid syndrome (APS), including secondary
      prophylaxis in the setting of venous and arterial thrombosis, as well as
      treatment for the prevention of recurrent miscarriages and fetal death. The role
      of primary thromboprophylaxis is also discussed in depth. Great emphasis is given
      to incorporating the most up-to-date and relevant evidence base both from the APS
      literature, and from large, recent, randomized controlled trials (RCTs) of
      primary and secondary thrombotic prophylaxis in the general population setting
      (ie, the population that has not been specifically investigated for APS).

PMID- 19587373
TI  - A novel binding site for ADAMTS13 constitutively exposed on the surface of
      globular VWF.
AB  - ADAMTS13 metalloprotease regulates the multimeric size of von Willebrand factor
      (VWF) by cleaving the Tyr1605-Met1606 bond in the VWF A2 domain. The mechanisms
      of VWF recognition by ADAMTS13 have yet to be fully resolved. Most studies have
      focused on the role of exosites within the VWF A2 domain, involved in interaction
      with the ADAMTS13 spacer domain. In the present study, we expressed different C
      terminal domain VWF fragments and evaluated their binding to ADAMTS13 and its
      truncated mutants, MDTCS and del(TSP5-CUB). Using plate binding assay and surface
      plasmon resonance, we identified a novel ADAMTS13 binding site (K(D)
      approximately 86 nM) in the region of VWF spanning residues 1874 to 2813, which
      includes the VWF D4 domain and that interacts with the C-terminal domains of
      ADAMTS13. We show that the interaction occurs even when VWF is in static
      conditions, assumed to be globular and where the VWF A2 domain is hidden. We
      demonstrate that C-terminal VWF fragments, as well as an antibody specifically
      directed toward the VWF D4 domain, inhibit VWF proteolysis by ADAMTS13 under
      shear conditions. We propose that this novel VWF C-terminal binding site may
      participate as the initial step of a multistep interaction ultimately leading to
      proteolysis of VWF by ADAMTS13.

PMID- 19587375
TI  - Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide
      important prognostic information in AML.
AB  - Nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML), which is recognized as
      a provisional entity in the World Health Organization 2008 classification of
      myeloid neoplasms, accounts for 30% of AML. We analyzed 1227 diagnostic and
      follow-up samples in 252 NPM1-mutated AML patients with 17 different NPM1
      mutation-specific real-time quantitative polymerase chain reaction (RQ-PCR)
      assays. Paired diagnostic/relapse samples of 84 patients revealed stable NPM1
      mutations in all cases, suggesting that they are pathogenetically early events
      and thus applicable for minimal residual disease detection. A total of 47
      relapses were predictable because of an NPM1 mutation level (%NPM1/ABL1) increase
      of at least 1 log or in 15 cases because of NPM1 mutation levels not decreasing
      less than 3 log ranges. A high prognostic value of NPM1 levels was shown for 4
      different intervals after therapy was initiated. Furthermore, thresholds of 0.1
      and 0.01%NPM1/ABL1 during/after treatment discriminated between prognostic
      subgroups. Univariate analyses, including age, white blood cell count, blast
      count, CD34 positivity, FLT3 mutations status, FAB type, karyotype, NPM1 mutation
      type, and pretreatment NPM1 mutational level, showed that, besides NPM1 mutation
      level, only age and FLT3-LM mutation status were prognostically significant for
      EFS. Multivariate analysis, including age, FLT3-LM status, and NPM1 mutation
      level at different time points, demonstrated that NPM1 level was the most
      relevant prognostic factor during first-line treatment. Similar results were
      obtained in patients undergoing second-line chemotherapy or allogeneic stem cell
      transplantation.

PMID- 19587376
TI  - Toll-like receptors mediate induction of hepcidin in mice infected with Borrelia
      burgdorferi.
AB  - Hepcidin is the major regulator of systemic iron homeostasis in mammals. Hepcidin
      is produced mainly by the liver and is increased by inflammation, leading to
      hypoferremia. We measured serum levels of bioactive hepcidin and its effects on
      serum iron levels in mice infected with Borrelia burgdorferi. Bioactive hepcidin
      was elevated in the serum of mice resulting in hypoferremia. Infected mice
      produced hepcidin in both liver and spleen. Both intact and sonicated B
      burgdorferi induced hepcidin expression in cultured mouse bone marrrow
      macrophages. Hepcidin production by cultured macrophages represents a primary
      transcriptional response stimulated by B burgdorferi and not a secondary
      consequence of cytokine elaboration. Hepcidin expression induced by B burgdorferi
      was mediated primarily by activation of Toll-like receptor 2.

PMID- 19587377
TI  - Characterization of Gaucher disease bone marrow mesenchymal stromal cells reveals
      an altered inflammatory secretome.
AB  - Gaucher disease causes pathologic skeletal changes that are not fully explained.
      Considering the important role of mesenchymal stromal cells (MSCs) in bone
      structural development and maintenance, we analyzed the cellular biochemistry of
      MSCs from an adult patient with Gaucher disease type 1 (N370S/L444P mutations).
      Gaucher MSCs possessed a low glucocerebrosidase activity and consequently had a 3
      fold increase in cellular glucosylceramide. Gaucher MSCs have a typical MSC
      marker phenotype, normal osteocytic and adipocytic differentiation, growth,
      exogenous lactosylceramide trafficking, cholesterol content, lysosomal
      morphology, and total lysosomal content, and a marked increase in COX-2,
      prostaglandin E2, interleukin-8, and CCL2 production compared with normal
      controls. Transcriptome analysis on normal MSCs treated with the
      glucocerebrosidase inhibitor conduritol B epoxide showed an up-regulation of an
      array of inflammatory mediators, including CCL2, and other differentially
      regulated pathways. These cells also showed a decrease in sphingosine-1
      phosphate. In conclusion, Gaucher disease MSCs display an altered secretome that
      could contribute to skeletal disease and immune disease manifestations in a
      manner distinct and additive to Gaucher macrophages themselves.

PMID- 19587379
TI  - Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T
      cells with superior antitumor activity and higher TCR functional avidity.
AB  - Adoptive transfer of T cells expressing transgenic T-cell receptors (TCRs) with
      antitumor function is a hopeful new therapy for patients with advanced tumors;
      however, there is a critical bottleneck in identifying high-affinity TCR
      specificities needed to treat different malignancies. We have developed a
      strategy using autologous dendritic cells cotransfected with RNA encoding an
      allogeneic major histocompatibility complex molecule and a tumor-associated
      antigen to obtain allo-restricted peptide-specific T cells having superior
      capacity to recognize tumor cells and higher functional avidity. This approach
      provides maximum flexibility because any major histocompatibility complex
      molecule and any tumor-associated antigen can be combined in the dendritic cells
      used for priming of autologous T cells. TCRs of allo-restricted T cells, when
      expressed as transgenes in activated peripheral blood lymphocytes, transferred
      superior function compared with self-restricted TCR. This approach allows high
      avidity T cells and TCR specific for tumor-associated self-peptides to be easily
      obtained for direct adoptive T-cell therapy or for isolation of therapeutic
      transgenic TCR sequences.

PMID- 19587378
TI  - Identification of novel antigens with induced immune response in monoclonal
      gammopathy of undetermined significance.
AB  - The transformation from monoclonal gammopathy of undetermined significance (MGUS)
      to multiple myeloma (MM) is thought to be associated with changes in immune
      processes. We have therefore used serologic analysis of recombinant cDNA
      expression library to screen the sera of MGUS patients to identify tumor
      associated antigens. A total of 10 antigens were identified, with specific
      antibody responses in MGUS. Responses appeared to be directed against
      intracellular proteins involved in cellular functions, such as apoptosis (SON,
      IFT57/HIPPI), DNA and RNA binding (ZNF292, GPATCH4), signal transduction
      regulators (AKAP11), transcriptional corepressor (IRF2BP2), developmental
      proteins (OFD1), and proteins of the ubiquitin-proteasome pathway (PSMC1).
      Importantly, the gene responsible for the oral-facial-digital type I syndrome
      (OFD1) had response in 6 of 29 (20.6%) MGUS patients but 0 of 11 newly diagnosed
      MM patients. Interestingly, 3 of 11 (27.2%) MM patients after autologous stem
      cell transplantations showed responses to OFD1. We have confirmed T-cell
      responses against OFD1 in MGUS and observed down-regulation of GLI1/PTCH1 and p
      beta-catenin after OFD1 knock-down with specific siRNA, suggesting its functional
      role in the regulation of Hh and Wnt pathways. These findings demonstrate OFD1 as
      an important immune target and highlight its possible role in signal transduction
      and tumorigenesis in MGUS and MM.

PMID- 19587380
TI  - Endothelial cell protein C receptor cellular localization and trafficking:
      potential functional implications.
AB  - Although the binding of endothelial cell protein C receptor (EPCR) to its ligands
      is well characterized at the biochemical level, it remains unclear how EPCR
      interaction with its ligands at the cell surface impacts its cellular
      trafficking. We characterized the cellular localization and trafficking of EPCR
      in endothelial cells and a heterologous expression system. Immunofluorescence
      confocal microscopy studies revealed that a majority of EPCR is localized on the
      cell surface in membrane microdomains that are positive for caveolin-1. A small
      fraction of EPCR is also localized intracellularly in the recycling compartment.
      Factor VIIa (FVIIa) or activated protein C binding to EPCR promoted the
      internalization of EPCR. EPCR and EPCR-bound ligands were endocytosed rapidly via
      a dynamin- and caveolar-dependent pathway. The endocytosed receptor-ligand
      complexes were accumulated in a recycling compartment before being targeted back
      to the cell surface. EPCR-mediated FVIIa endocytosis/recycling also resulted in
      transport of FVIIa from the apical to the basal side. In vivo studies in mice
      showed that blockade of EPCR with EPCR-blocking antibodies impaired the early
      phase of FVIIa clearance. Overall, our results show that FVIIa or activated
      protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated
      endocytosis may facilitate the transcytosis of FVIIa and its clearance from the
      circulation.

PMID- 19587382
TI  - Discriminative and predictive validity of the penile plethysmograph in adolescent
      sex offenders.
AB  - The current study addresses the discriminative and predictive validity of the
      penile plethysmograph (PPG) in a sample of 132 male adolescent sex offenders who
      were admitted to a sex offender treatment program. The subjects were assessed
      pretreatment and posttreatment, under two different instructions sets: an Arouse
      condition, where subjects allowed themselves to become aroused; and a Suppress
      condition, where subjects attempted to suppress or control their arousal. Under
      the pretreatment Arouse condition, the group with male child victims demonstrated
      significantly greater arousal to child stimuli than the group with female
      nonchild victims. However, the group with female child victims could not be
      differentiated from the group with female nonchild victims. Under the Suppress
      condition, there was no evidence of discriminative validity for any of the PPG
      indices. As for predictive validity, posttreatment arousal to male and female
      children was significantly related to sexual offense recidivism. Posttreatment
      inability to suppress deviant arousal to male and female children was also
      significantly related to sexual offense recidivism over the 6-year follow-up
      period. In light of these findings, the implications for adolescent sex offender
      research and treatment are discussed.

PMID- 19587381
TI  - M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates
      SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage
      specification.
AB  - The role of hematopoietic cytokines in lineage commitment remains uncertain. To
      gain insight into the contribution of cytokine signaling to myeloid lineage
      specification, we compared granulocyte colony-stimulating factor (G-CSF) and
      macrophage colony-stimulating factor (M-CSF) signaling in Ba/F3 cells expressing
      both the G-CSF and M-CSF receptors and in lineage-negative murine marrow cells. G
      CSF and M-CSF serve as prototypes for additional cytokines that also influence
      immature myeloid cells. G-CSF specifically activated signal transducer and
      activator of transcription 3 and induced Src homology region 2 domain-containing
      phosphatase 2 (SHP2) phosphorylation, whereas M-CSF preferentially activated
      phospholipase Cgamma2, and thereby extracellular signal-regulated kinase (ERK),
      to stabilize c-Fos and stimulate CCAAT/enhancer-binding protein (C/EBP)alpha(S21)
      phosphorylation. In contrast, activation of Jun kinase or c-Jun was similar in
      response to either cytokine. Inhibition of ERK prevented induction of c-Fos by M
      CSF and reduced C/EBPalpha phosphorylation and formation of colony-forming unit
      monocytes. SHP2 inhibition reduced ERK activation in G-CSF, but not M-CSF, and
      reduced colony-forming unit-granulocytes, underscoring divergent pathways to ERK
      activation. Phorbol ester mimicked the effect of M-CSF, activating ERK
      independent of SHP2. In summary, M-CSF activates ERK more potently than G-CSF,
      and thereby induces higher levels of c-Fos and phospho-C/EBPalpha(S21), which may
      directly interact to favor monopoiesis, whereas G-CSF activates signal transducer
      and activator of transcription 3 and SHP2, potentially shifting the balance to
      granulopoiesis via gene induction by C/EBPalpha homodimers and via effects of
      SHP2 on regulators besides ERK.

PMID- 19587383
TI  - Laparoscopic surgery improves blood glucose homeostasis and insulin resistance
      following distal gastrectomy for cancer.
AB  - BACKGROUND: Prevention of blood glucose elevation and insulin resistance could be
      more pronounced in patients undergoing laparoscopic rather than open gastrectomy.
      METHODS: Fifty-seven patients underwent distal gastrectomy by either laparoscopy
      (n = 36) or an open approach (n = 21). Blood glucose, serum insulin, and the
      daily insulin secretion rate (urinary C-peptide) were measured. Insulin
      resistance was evaluated using an adapted homeostasis model assessment of insulin
      resistance (HOMA-R). RESULTS: Blood glucose levels were lower in the laparoscopy
      group than in the open group on the operative day and on postoperative days (POD)
      1 and 3 (P < .001, P = .001, and P = .024, respectively). Serum insulin levels
      were lower in the laparoscopy group than in the open group on POD 1 and 3 (P =
      .045 and P = .027, respectively). HOMA-R was lower in the laparoscopy group than
      in the open group on POD 1 and 3 (P = .024 and P = .009, respectively). Daily
      insulin secretion rates were lower in the laparoscopy group than in the open
      group on POD 1 (P = .023). CONCLUSIONS: Laparoscopic surgery prevents blood
      glucose elevation and improves insulin resistance compared with open surgery.

PMID- 19587384
TI  - Low availability of aluminum in formulations for parenteral nutrition containing
      silicate.
AB  - BACKGROUND: Silicate (Si) and aluminum (Al) may be concomitant impurities in
      solutions for parenteral nutrition (PN). Silicate can bind to Al to form stable
      hydroxyaluminosilicates (HAS), thus reducing Al availability. This possibility is
      investigated by heating solutions containing constituents of PN in glass
      containers to promote the release of Si and Al. METHODS: The total amount of Si
      and Al in solution is measured by atomic absorption spectrometry, and the Al not
      bound to Si is evaluated by reaction with morin. RESULTS: When the Si:Al molar
      ratio is >5, no free Al is found in solution. For ratios <5, it is found that the
      lower the ratio, the higher the free Al fraction. However, in solutions of some
      amino acids, even with a low Si:Al ratio (<2), the amount of free Al is lower
      than that found in other solutions. The same tendency is observed among
      commercial formulations. Although in salt solutions the free fraction of Al
      reaches almost 100% when the Si concentration is low, in amino acid formulations
      the free fraction of Al does not surpass 50%. Moreover, even for Si:Al ratios >5,
      there is a "residual" fraction of free Al in amino acid formulations.
      CONCLUSIONS: The concomitant presence of Al and Si in solutions for PN reduces
      the amount of Al available attributable to the formation of HAS. In amino acid
      formulations this effect may be slightly reduced given the affinity of certain
      amino acids for Al. Therefore, amino acids may behave in the same fashion as
      silicate.

PMID- 19587385
TI  - High rates of mortality and morbidity occur in infants with parenteral nutrition
      associated cholestasis.
AB  - BACKGROUND: Extremely few data are available about the natural history of
      parenteral nutrition (PN)-associated cholestasis. The authors evaluated a cohort
      of infants at a large center to determine the outcome of PN-associated
      cholestasis in infants with some gastrointestinal function. METHODS: The authors
      reviewed the records of all infants admitted to a level 3 neonatal intensive care
      unit over a 16-month period who had the diagnosis of PN-associated cholestasis.
      Records were reviewed in these infants for course of cholestasis, laboratory
      values, outcome, and infection rate. RESULTS: Sixty-six patients were admitted
      who met the study criteria. There were 10 deaths and 1 referral for liver
      transplant (Death/TPlant) (17%) in the first year of life. All Death/TPlant
      infants had at least 1 positive blood culture after the onset of cholestasis.
      Maximum conjugated bilirubin (MaxCB) in Death/TPlant infants was 15.7 +/- 2.2
      (SEM) compared to 8.4 +/- 1.0 mg/dL in babies who recovered. Of 21 infants with a
      MaxCB > or =10.0, Death/TPlant occurred in 8/21 (38%). Of 40 babies with positive
      blood cultures, 11 were in the Death/TPlant group vs no deaths among the 25
      without positive blood cultures. Average time to resolution from the MaxCB to a
      CB <2.0 mg/dL was 66 +/- 7 days (n = 49). CONCLUSIONS: Infants with PN-associated
      cholestasis have high rates of mortality despite the presence of some
      gastrointestinal function. These data support further evaluation and the
      development of novel forms of therapy for babies with parenteral-associated CB >
      or =2 mg/dL with emphasis on interventions for infants with a CB >10 mg/dL.

PMID- 19587386
TI  - Clinical application of magnetic resonance spectroscopy of the liver in patients
      receiving long-term parenteral nutrition.
AB  - BACKGROUND: Intestinal failure-associated liver disease (IFALD) may have
      progressed to an advanced stage by the time it becomes evident via laboratory or
      physical signs. A safe, noninvasive technique for assessing the liver could
      significantly aid in monitoring the effects of therapeutic intervention, improve
      the timing of liver and small intestinal transplantation, and increase our
      understanding of the causes of IFALD. METHODS: Six female patients fed
      intravenously for >1 year and 6 controls matched for body mass index (BMI)
      underwent liver magnetic resonance scanning with acquisition of (1)H and (31)P
      resonance spectra. Areas under the curve for lipid (the sum of CH, CH(2), and
      CH(3)), water, and choline peaks were calculated and expressed semi
      quantitatively as ratios of lipid:water and choline:lipid. Phosphomonoester (PME)
      and phosphodiester (PDE) peak areas were similarly expressed as a ratio. Controls
      and cases were compared using Mann-Whitney U test; least squares regression
      analysis was used to compare the effect of measured variables on the lipid:water
      peak area ratio. RESULTS: Patients and controls were well matched for BMI.
      Parenteral feeding was associated with a highly significant increase in
      lipid:water peak ratio (P < .005). Choline:lipid (P < .05) and choline:water (not
      significant) ratios were reduced in patients compared with controls. The increase
      in lipid:water ratios in patients was independent of BMI and choline:water
      ratios. A ratio of PME:PDE of >0.3 (and >3 SD from the control mean) predicted
      the 2 patients at most risk of advanced liver disease. CONCLUSIONS: This pilot
      study confirms the potential of magnetic resonance spectroscopic techniques in
      evaluating IFALD and could contribute significantly to our understanding and
      management of this condition.

PMID- 19587387
TI  - Understanding the paradox of patient pain and patient satisfaction.
AB  - Pain, in all probability, is the most common symptom experienced by individuals
      who interact with health care providers. It is understood as a complex and highly
      individual experience. This complexity is reflected in the paradoxical
      relationship between patient satisfaction and patient reported pain scores. Using
      a holistic, caring approach, nurses can optimize the effect of analgesia and
      facilitate comfort for the person living in pain. Caring for the patient in pain
      begins with heartfelt compassion and intention to help the person who is
      suffering. The author describes how the complex relationship and interchange
      between the patient and the holistic nurse explains the paradox.

PMID- 19587388
TI  - Improved pain, physical functioning and health status in patients with rheumatoid
      arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor:
      results from a randomised, double-blind, placebo-controlled trial.
AB  - OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function
      and health status in patients with moderate to severe active rheumatoid arthritis
      (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha
      inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15
      or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's
      assessment of arthritis pain (pain), patient's assessment of disease activity,
      Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF
      36) were recorded. RESULTS: At week 6, significantly more patients in the CP
      690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain
      compared with placebo (44%, 66%, 78% and 14%, respectively), clinically
      meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%,
      respectively) and clinically meaningful improvements in SF-36 domains and
      physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in
      improving the pain, function and health status of patients with RA, from week 1
      to week 6.

PMID- 19587389
TI  - Inflammatory biomarkers and the prediction of coronary events among people at
      intermediate risk: the EPIC-Norfolk prospective population study.
AB  - OBJECTIVE: To evaluate the role of the inflammatory biomarkers C-reactive protein
      (CRP), myeloperoxidase, paraoxonase, secretory phospholipase A2 group IIA
      (sPLA2), lipoprotein-associated phospholipase A2, fibrinogen, macrophage
      chemoattractant protein-1 and adiponectin, in predicting the risk of coronary
      heart disease (CHD) among people estimated to be at intermediate risk according
      to the Framingham Risk Score (FRS). DESIGN: Prospective case-control study nested
      in EPIC-Norfolk cohort. SETTING: Norfolk, UK. PATIENTS: Apparently healthy men
      and women aged 45-79 years. MAIN OUTCOME MEASURES: Risk of future coronary artery
      disease. RESULTS: For participants predicted to be at intermediate risk by the
      FRS, the highest c statistics were observed for FRS plus CRP (0.61, 95% CI 0.57
      to 0.65) and for FRS plus sPLA2 (0.56, 95% CI 0.52 to 0.6). Net correct
      reclassification of cases and controls for each marker was assessed for people
      across the entire risk spectrum and again for people at intermediate risk only.
      The largest differences were observed for CRP, 12.0% net reclassification
      improvement in the entire risk spectrum and 28.4% net reclassification
      improvement in the intermediate-risk group and for sPLA2, the net
      reclassification improvement was 6.4% in the entire risk spectrum and 16.3% in
      the intermediate-risk group. CONCLUSIONS: The discriminatory potential of
      inflammatory biomarkers was substantially different when analysed across the
      entire risk spectrum compared with the subgroup of people at intermediate risk.

PMID- 19587390
TI  - Improving survival in the 6 months after diagnosis of heart failure in the past
      decade: population-based data from the UK.
AB  - OBJECTIVE: To investigate the secular trend in survival after a new diagnosis of
      heart failure in the UK population. DESIGN AND SETTING: Comparison of all-cause
      mortality in the 6 months after diagnosis of heart failure in population-based
      studies in the south east of England in 2004-5 (Hillingdon-Hastings Study) and
      1995-7 (Hillingdon-Bromley Studies). PARTICIPANTS: 396 patients in the 2004-5
      cohort and 552 patients in the 1995-7 cohort with incident (new) heart failure.
      MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: All-cause mortality rates
      were 6% (95% CI 3% to 8%) at 1 month, 11% (8% to 14%) at 3 months and 14% (11% to
      18%) at 6 months in the 2004-5 cohort compared with 16% (13% to 20%), 22% (19% to
      25%) and 26% (22% to 29%), respectively, in the 1995-7 cohort (difference between
      the two cohorts, p<0.001). The difference in survival was not explained by any
      difference in the demographics or severity of heart failure at presentation.
      There was a difference at baseline and thereafter in the use of neurohormonal
      antagonists (beta-blockers and angiotensin-converting enzyme inhibitors).
      CONCLUSIONS: Although early mortality remains high among patients with newly
      diagnosed heart failure in the UK general population, there is strong evidence of
      a marked improvement in survival from 1995-7 to 2004-5, perhaps partly explained
      by an increased usage of neurohormonal antagonists.

PMID- 19587391
TI  - The Rehabilitation Complexity Scale version 2: a clinimetric evaluation in
      patients with severe complex neurodisability.
AB  - OBJECTIVE: To evaluate the clinimetric properties of the Rehabilitation
      Complexity Scale (RCS) in a neurorehabilitation inpatient sample. DESIGN:
      Observational cohort analysis in a tertiary specialist setting. SUBJECTS: 179
      consecutive patients (mean age 44.5 years (SD 15 years), males:females 110:69)
      with complex neurological disabilities, mainly following acquired brain injury.
      METHODS: Repeat RCS ratings of the level of care, nursing, therapy and medical
      interventions were examined for dimensionality, repeatability, consistency and
      responsiveness, and compared with the Northwick Park Nursing and Therapy
      Dependency Scales, the Functional Independence Measure (FIM) and Barthel Index,
      recorded at the start and end of treatment. RESULTS: The test-retest reliability
      confirmed the RCS to be repeatable (kappa 0.93 to 0.96) and moderately responsive
      to changes in levels of intervention over the course of the programme, suggesting
      the need for serial evaluation. Coefficient-alpha was 0.76 and item-total
      correlations all >0.50, with moderate to high loadings on the first principal
      component. Factor analysis revealed two clear factors ('Nursing/medical care,'
      and 'Therapies'). The RCS demonstrated good convergent and discriminant validity
      with the Northwick Park Nursing and Therapy Dependency Scales but some ceiling
      effect. FIM motor and Barthel scores correlated well with basic care and nursing
      scores (Spearman rho -0.65 to -0.79) but less well with therapy (rho -0.26) and
      medical (rho -0.28 to -0.33) scores. CONCLUSION: In this cohort, the RCS provided
      a reliable, valid and moderately responsive profile of rehabilitation
      interventions, separating into two main subscales. It usefully identified medical
      and therapy inputs not captured by the FIM and Barthel Index, which are commonly
      used to define case complexity in rehabilitation.

PMID- 19587392
TI  - Mycoplasma genitalium in asymptomatic patients: implications for screening.
AB  - OBJECTIVES: Mycoplasma genitalium is well established as a cause of urethritis
      and has also been associated with cervicitis, endometritis and pelvic infection.
      Low rates of infection suggest screening may be inappropriate in the general
      population, but it remains unclear whether asymptomatic patients attending a
      sexual-health clinic should be tested routinely. The objective of this study was
      to measure the positivity rate of M genitalium infection in asymptomatic
      individuals presenting to a sexual-health clinic to inform the need for screening
      in this population. METHODS: Asymptomatic patients were identified using a
      structured questionnaire and tested for M genitalium from genital swabs or urine
      using two separate polymerase chain reaction (PCR) assays incorporating different
      primer sequences. RESULTS: 1304 patients were approached over a 6-month period.
      743 (57%) patients were symptomatic, and 168 (13%) refused consent, leaving 394
      (30%) patients who entered the study. Residual samples were available for 308
      (79%) patients, 168 (54%) men and 140 (46%) women. 14/308 (4.5%, 95% CI 2.2 to
      6.9%) asymptomatic patients were infected with M genitalium, and an additional 2
      (0.6%, 95% CI 0.2 to 2.3%) patients had discrepant PCR results. No significant
      associations were found between M genitalium infection and age, gender, ethnicity
      or isolation site. CONCLUSION: The positivity rate of M genitalium infection in
      asymptomatic sexual-health clinic attendees is comparable with that of gonorrhoea
      or chlamydia, and, if evidence of pathogenicity continues to accumulate, a
      further assessment of the role of routine screening in this setting would be
      appropriate.

PMID- 19587393
TI  - Improving spike separation using waveform derivatives.
AB  - This paper presents spike derivatives as a tool for spike feature extraction to
      improve the separation of similar neurons. The theoretical framework of neuronal
      geometry signatures and noise shaping to perform the spike derivative is
      formulated first, and based on the derivations we show that the first derivative
      of the spikes manifests the waveform difference contributed by the geometry
      signatures and also reduces the associated low-frequency noise. Quantitative
      comparisons of sorting neurons using spikes and their derivatives are performed
      on spike sequences from a public database, and improved results are observed when
      using spike derivatives.

PMID- 19587394
TI  - Impedance characteristics of deep brain stimulation electrodes in vitro and in
      vivo.
AB  - The objective of this study was to quantify the electrode-tissue interface
      impedance of electrodes used for deep brain stimulation (DBS). We measured the
      impedance of DBS electrodes using electrochemical impedance spectroscopy in vitro
      in a carbonate- and phosphate-buffered saline solution and in vivo following
      acute implantation in the brain. The components of the impedance, including the
      series resistance (R(s)), the Faradaic resistance (R(f)) and the double layer
      capacitance (C(dl)), were estimated using an equivalent electrical circuit. Both
      R(f) and C(dl) decreased as the sinusoidal frequency was increased, but the ratio
      of the capacitive charge transfer to the Faradaic charge transfer was relatively
      insensitive to the change of frequency. R(f) decreased and C(dl) increased as the
      current density was increased, and above a critical current density the interface
      impedance became nonlinear. Thus, the magnitude of the interface impedance was
      strongly dependent on the intensity (pulse amplitude and duration) of
      stimulation. The temporal dependence and spatial non-uniformity of R(f) and C(dl)
      suggested that a distributed network, with each element of the network having
      dynamics tailored to a specific stimulus waveform, is required to describe
      adequately the impedance of the DBS electrode-tissue interface. Voltage
      transients to biphasic square current pulses were measured and suggested that the
      electrode-tissue interface did not operate in a linear range at clinically
      relevant current amplitudes, and that the assumption of the DBS electrode being
      ideally polarizable was not valid under clinical stimulating conditions.

PMID- 19587395
TI  - Decentralized adaptive robust control based on sliding mode and nonlinear
      compensator for the control of ankle movement using functional electrical
      stimulation of agonist-antagonist muscles.
AB  - A decentralized control methodology is designed for the control of ankle
      dorsiflexion and plantarflexion in paraplegic subjects with electrical
      stimulation of tibialis anterior and calf muscles. Each muscle joint is
      considered as a subsystem and individual controllers are designed for each
      subsystem. Each controller operates solely on its associated subsystem, with no
      exchange of information between the subsystems. The interactions between the
      subsystems are taken as external disturbances for each isolated subsystem. In
      order to achieve robustness with respect to external disturbances, unmodeled
      dynamics, model uncertainty and time-varying properties of muscle-joint dynamics,
      a robust control framework is proposed which is based on the synergistic
      combination of an adaptive nonlinear compensator with a sliding mode control and
      is referred to as an adaptive robust control. Extensive simulations and
      experiments on healthy and paraplegic subjects were performed to demonstrate the
      robustness against the time-varying properties of muscle-joint dynamics, day-to
      day variations, subject-to-subject variations, fast convergence, stability and
      tracking accuracy of the proposed method. The results indicate that the
      decentralized robust control provides excellent tracking control for different
      reference trajectories and can generate control signals to compensate the muscle
      fatigue and reject the external disturbance. Moreover, the controller is able to
      automatically regulate the interaction between agonist and antagonist muscles
      under different conditions of operating without any preprogrammed antagonist
      activities.

PMID- 19587396
TI  - Sewer infiltration/inflow: long-term monitoring based on diurnal variation of
      pollutant mass flux.
AB  - The paper deals with a method for quantification of infiltrating groundwater
      based on the variation of diurnal pollutant load and continuous water quality and
      quantity monitoring. Although the method gives us the potential to separate
      particular components of wastewater hygrograph, several aspects of the method
      should be discussed. Therefore, the paper investigates the cost-effectiveness,
      the relevance of pollutant load from surface waters (groundwater) and the
      influence of measurement time step. These aspects were studied in an experimental
      catchment of Prague sewer system, Czech Republic, within a three-month period.
      The results indicate high contribution of parasitic waters on night minimal
      discharge. Taking into account the uncertainty of the results and time-consuming
      maintenance of the sensor, the principal advantages of the method are evaluated.
      The study introduces a promising potential of the discussed measuring concept for
      quantification of groundwater infiltrating into the sewer system. It is shown
      that the conventional approach is sufficient and cost-effective even in those
      catchments, where significant contribution of foul sewage in night minima would
      have been assumed.

PMID- 19587398
TI  - Modeling highway runoff pollutant levels using a data driven model.
AB  - Pollutants accumulated on road pavement during dry periods are washed off the
      surface with runoff water during rainfall events, presenting a potentially
      hazardous non-point source of pollution. Estimation of pollutant loads in these
      runoff waters is required for developing mitigation and management strategies,
      yet the numerous factors involved and their complex interconnected influences
      make straightforward assessment almost impossible. Data driven models (DDMs) have
      lately been used in water and environmental research and have shown very good
      prediction ability. The proposed methodology of a coupled MT-GA model provides an
      effective, accurate and easily calibrated predictive model for EMC of highway
      runoff pollutants. The models were trained and verified using a comprehensive
      data set of runoff events monitored in various highways in California, USA. EMCs
      of Cr, Pb, Zn, TOC and TSS were modeled, using different combinations of
      explanatory variables. The models' prediction ability in terms of correlation
      between predicted and actual values of both training and verification data was
      mostly higher than previously reported values. Pb(Total) was modeled with an
      outcome of R2 of 0.95 on training data and 0.43 on verification data. The
      developed model for TOC achieved R2 values of 0.91 and 0.49 on training and
      verification data respectively.

PMID- 19587399
TI  - Laboratory investigation on the performances of baffles for the capture of sewer
      floatables.
AB  - The use of baffles in sewer systems enables the capture of floatables, which
      could be responsible for both malfunctioning of water treatment plants and
      aesthetic pollution of receiving bodies when discharges through combined sewer
      overflow devices occur. An experimental contribution to the understanding of
      capturing processes of floatable elements by means of baffle devices is presented
      in this paper. Experiments were carried out using different baffle
      configurations. The limit equilibrium conditions of various types of floatables,
      i.e the condition beyond which upstream intercepted floatables start to escape
      the baffle, were investigated. The dimensional analysis was used in order to
      generalize the results of the experiments and to compare the capturing
      performances of analysed baffle configurations.

PMID- 19587397
TI  - Influence of temperature on the hydrolysis, acidogenesis and methanogenesis in
      mesophilic anaerobic digestion: parameter identification and modeling
      application.
AB  - The effect of temperature on the kinetic parameters involved in the main
      reactions of the anaerobic digestion process was studied. Batch tests with
      starch, glucose and acetic acid as substrates for hydrolysis, acidogenesis and
      methanogenesis, respectively, were performed in a temperature range between 15
      and 45 degrees C. First order kinetics was assumed to determine the hydrolysis
      rate constant, while Monod and Haldane kinetics were considered for acidogenesis
      and methanogenesis, respectively. The results obtained showed that the anaerobic
      process is strongly influenced by temperature, with acidogenesis exerting the
      highest effect. The Cardinal Temperature Model 1 with an inflection point (CTM1)
      fitted properly the experimental data in the whole temperature range, except for
      the maximum degradation rate of acidogenesis. A simple case-study assessing the
      effect of temperature on an anaerobic CSTR performance indicated that with
      relatively simple substrates, like starch, the limiting reaction would change
      depending on temperature. However, when more complex substrates are used (e.g.
      sewage sludge), the hydrolysis might become more quickly into the limiting step.

PMID- 19587400
TI  - Development and validation of a simplified model for the anaerobic degradation of
      phenol.
AB  - The anaerobic treatment of phenolic wastewater has demonstrated to be a suitable
      biological system, for that reason, a large number of systems have been
      implemented in a lab/pilot scale, several industrial plants have also been
      developed. Despite of this, there is a lack of modeling applications within these
      systems. In order to enhance the anaerobic treatment of this kind of water, a
      simplified model of 2 populations and 3 reactions was developed and implemented.
      The parameter calibration and the model validation were carried out with
      experimental data obtained from an Anaerobic Sequencing Batch Reactor treating
      phenolic wastewater through two different operational strategies: sequential
      batches with a co-substrate and sequential fed-batches without a co-substrate.
      The model predicted the reactors performance accurately for the different
      experimental conditions tested. Therefore, the theoretical basis of the model is,
      in general terms, valid, and its utilization to predict the reactors performance
      or in control purposes is feasible.

PMID- 19587401
TI  - Science-policy interfacing in support of the Water Framework Directive
      implementation.
AB  - Many current water-related RTD projects have established operational links with
      practitioners, which allow the needs of policy makers to be taken into account.
      However, RTD results are not easily available to water policy implementers and
      research scientists may lack insight in the needs of policy makers and
      implementers (i.e. the European Commission and water managers). The SPI-Water
      project worked out a number of concrete actions to bridge these gaps in
      communication by developing and implementing a 'science-policy interface',
      enhancing the use of RTD results in the Water Framework Directive (WFD)
      implementation. This project is part of a wider EC perspective aiming to bridge
      the gap between science and policy, specifically with respect to the WFD
      implementation. As a first action, existing science-policy links are
      investigated. RTD and LIFE projects that are of direct relevance for the
      implementation of the WFD are identified and analysed. Secondly, an information
      system (Harmoni-CA's WISE RTD Web Portal) has been further developed to cater for
      an efficient and easy to use tool for dissemination as well as retrieval of RTD
      results. As third action, this science-policy interfacing of WFD related topics
      are extended to non-EU countries taking into account their specific needs.

PMID- 19587402
TI  - In-sewer sedimentation associated with active flow control.
AB  - Active flow control using automated gates and weirs aims to utilise available
      dispersed storage within sewer systems to alleviate the severity and frequency of
      localised flooding incidents. Whilst a previous study has demonstrated its
      potential, a key operational concern before implementation was sedimentation. An
      experimental programme was designed to investigate the sediment deposition
      created when using a flow control device. Tests were also undertaken to examine
      the potential for rapid gate opening to flush away any resulting deposits. In
      catchments dominated by fine material in suspension, the use of an active flow
      control device can result in a uniformly thick deposit upstream of the gate.
      Rapid gate opening results in deposited material eroding in large sections
      starting at the gate and moving in an upstream direction. Granular sediment forms
      a series of discrete bedforms which are fairly uniform regardless of the flow
      conditions and a larger deposit further upstream. The potential for flushing
      granular deposits is limited and modification of the operation of the gate has
      shown little potential for increasing the effectiveness. Therefore, active flow
      control using a single downstream gate may only be suitable in systems with fine
      material moving in suspension during dry weather flow and not where there is
      significant granular sediment.

PMID- 19587403
TI  - Metals pollution tracing in the sewerage network using the diffusive gradients in
      thin films technique.
AB  - Diffusive Gradients in Thin-films (DGT) is a quantitative, passive monitoring
      technique that can be used to measure concentrations of trace species in situ in
      solutions. Its potential for tracing metals pollution in the sewer system has
      been investigated by placing the DGT devices into sewage pumping stations and
      into manholes, to measure the concentration of certain metals in the catchment of
      a sewage treatment works with a known metals problem. In addition the methodology
      and procedure of using the DGT technique in sewers was investigated. Parameters
      such as temperature and pH were measured to ensure they were within the limits
      required by the DGT devices, and the optimum deployment time was examined. It was
      found that although the results given by the DGT technique could not be
      considered to be fully quantitative, they could be used to identify locations
      that were showing an excess concentration of metals, and hence trace pollution
      back to its source. The DGT technique is 'user friendly' and requires no
      complicated equipment for deployment or collection, and minimal training for use.
      It is thought that this is the first time that the DGT technique has been used in
      situ in sewers for metals pollution tracing.

PMID- 19587404
TI  - The effect of surface texture on evaporation, infiltration and storage properties
      of paved surfaces.
AB  - This paper concerns an investigation of evaporation, infiltration and detention
      storage on paved surfaces and the effect of surface texture and microtopography
      on these processes. A numerical model has been developed which represents the
      evaporation and infiltration processes on a nominally impervious surface as well
      as the depression storage due to the surface microtopography. The model was
      applied to semi-randomly generated surfaces and the results show the relationship
      between surface microtopography and initial storage losses.

PMID- 19587405
TI  - Alternative manifestations of actor responses to urban flooding: case studies
      from Bradford and Glasgow.
AB  - Flooding processes are complex and can occur throughout urban areas sometimes
      with devastating consequences. Traditionally flood risks have been managed
      through a combination of structural defence measures, warnings and emergency
      measures. More recently they have included development controls and land zoning
      policies. When such measures fail, individuals, authorities and the economy have
      to cope with the consequences. There is a growing realization that the resilience
      of individuals and institutions to floods and the risks from flooding need to be
      addressed. In the past few years there has been what some have referred to as a
      paradigm shift in the way responses to flooding are being conceptualized and the
      way this affects actors and actions. Based on fieldwork including interviews this
      paper presents two examples of actor and institutional responses to flooding
      events from the cities of Bradford and Glasgow in the United Kingdom.

PMID- 19587406
TI  - To what extent does variability of historical rainfall series influence extreme
      event statistics of sewer system surcharge and overflows?
AB  - In urban drainage modelling long-term extreme statistics has become an important
      basis for decision-making e.g. in connection with renovation projects. Therefore
      it is of great importance to minimize the uncertainties with regards to long-term
      prediction of maximum water levels and combined sewer overflow (CSO) in drainage
      systems. These uncertainties originate from large uncertainties regarding
      rainfall inputs, parameters, and assessment of return periods. This paper
      investigates how the choice of rainfall time series influences the extreme events
      statistics of max water levels in manholes and CSO volumes. Traditionally, long
      term rainfall series, from a local rain gauge, are unavailable. In the present
      case study, however, long and local rain series are available. 2 rainfall gauges
      have recorded events for approximately 9 years at 2 locations within the
      catchment. Beside these 2 gauges another 7 gauges are located at a distance of
      max 20 kilometers from the catchment. All gauges are included in the Danish
      national rain gauge system which was launched in 1976. The paper describes to
      what extent the extreme events statistics based on these 9 series diverge from
      each other and how this diversity can be handled, e.g. by introducing an
      "averaging procedure" based on the variability within the set of statistics. All
      simulations are performed by means of the MOUSE LTS model.

PMID- 19587407
TI  - Effectiveness of masking agents: outcome of a three-year study at pilot and full
      scales.
AB  - Commercial products used as masking or neutralizing agents against odour
      emissions from solid waste activities were investigated both at pilot scale and
      at three full scale sites. Twenty-six products were first characterized and
      classified as potential masking or neutralizing agents. Four of the products
      tested at pilot scale revealed a masking efficiency and a significant decrease of
      the discomfort index. No evidence of neutralization effect was observed during
      the field tests.

PMID- 19587408
TI  - In sewer processes: mathematical model development and sensitivity analysis.
AB  - Until now the majority of sewer networks in Italy have been built and managed
      considering small as well as local wastewater treatment plants (WWTPs). However,
      pushed by Italian and EU regulations, centralised and large WWTPs are becoming
      more common in Italy. One major technical aspect caused by the changing from
      local to centralised WWTPs is the development of significant in-sewer processes.
      These processes are also emphasized by the building of long interceptor sewers
      characterized by high hydraulic retention times and absence of tributary sewers.
      In this paper a model derived from the well known WATS model (Wastewater
      Aerobic/anaerobic Transformation in Sewers) has been set up and applied to an
      Italian case study located in Palermo. To assure a good degree of reliability the
      model needs a number of parameters that can be measured or calibrated by the
      combined use of field data and laboratory analyses. To support the planning of
      the experimental activity a sensitivity analysis to assess the influence of each
      model parameter has been carried out. Indeed, the sensitivity analysis allowed
      identifying the most significant model parameters. As a matter of the fact, by
      means of sensitivity analysis it was possible not only to pin down the most
      important model parameters but also to address the field survey towards the most
      sensitive model parameters in order to optimize the model application. The
      results are interesting and enabled to reduce the number of parameters to be
      calibrated from 24 to 14. More specifically, COD fractions, Y(Hw) and mu(H)
      showed a strong influence on the model results addressing the field campaign to
      an accurate evaluation of their value.

PMID- 19587409
TI  - Ultrasonic device for real-time sewage velocity and suspended particles
      concentration measurements.
AB  - In the frame of a technological research and innovation network in water and
      environment technologies (RITEAU, Reseau de Recherche et d'Innovation
      Technologique Eau et Environnement), our research group, in collaboration with
      industrial partners and other research institutions, has been in charge of the
      development of a suitable flowmeter: an ultrasonic device measuring
      simultaneously the water flow and the concentration of size classes of suspended
      particles. Working on the pulsed ultrasound principle, our multi-frequency device
      (1 to 14 MHz) allows flow velocity and water height measurement and estimation of
      suspended solids concentration. Velocity measurements rely on the coherent
      Doppler principle. A self developed frequency estimator, so called Spectral
      Identification method, was used and compared to the classical Pulse-Pair method.
      Several measurements campaigns on one wastewater collector of the French city of
      Strasbourg gave very satisfactory results and showed smaller standard deviation
      values for the Doppler frequency extracted by the Spectral Identification method.
      A specific algorithm was also developed for the water height measurements. It
      relies on the water surface acoustic impedance rupture and its peak localisation
      and behaviour in the collected backscattering data. This algorithm was positively
      tested on long time measurements on the same wastewater collector. A large part
      of the article is devoted to the measurements of the suspended solids
      concentrations. Our data analysis consists in the adaptation of the well
      described acoustic behaviour of sand to the behaviour of wastewater particles.
      Both acoustic attenuation and acoustic backscattering data over multiple
      frequencies are analyzed for the extrapolation of size classes and respective
      concentrations. Under dry weather conditions, the massic backscattering
      coefficient and the overall size distribution showed similar evolution whatever
      the measurement site was and were suggesting a global wastewater particles
      behaviour. By comparison to sampling data, our data analysis lead to the
      characterization of two particle groups: the ones occurring during rain events
      and the ones typical of wastewater under dry weather conditions. Even with
      already encouraging results on the several weeks of data recorded on several
      wastewater collectors, the validation of our data inversion method is still under
      progress.

PMID- 19587410
TI  - Bacterial pollution of the riverine surface microlayer and subsurface water.
AB  - The density and distribution of bacteria indicative of pollution in the surface
      microlayer and subsurface water of the River Slupia were estimated. The number of
      heterotrophic bacteria, total coliforms, fecal coliforms and fecal streptococci
      were higher in the surface microlayer than in the underlying water. The average
      bacterial enrichment factor (EF) of the parameters studied in the bacterioneuston
      was 1.7 to 1.8 times higher than in bacterioplankton. During the annual study
      cycle, bacterial pollution indicators inhabiting the surface microlayer and
      subsurface water showed considerable monthly changes.

PMID- 19587411
TI  - Nitrogen enriched dissolved organic matter (DOM) isolates and their affinity to
      form emerging disinfection by-products.
AB  - Increased contributions from wastewater discharges and algal activity in drinking
      water supplies can lead to elevated levels of dissolved organic nitrogen (DON),
      which can increase the likelihood for the formation of emerging nitrogenous
      disinfection by-products (N-DBPs) of health concern. Dissolved organic matter
      (DOM) isolated from five waters, using a newly developed DOM isolation method
      specific to DON fractionation, produced thirty-four isolates of suitable mass.
      Each isolate was treated with free chlorine or chloramines under formation
      potential conditions. The DBP yields were determined for three halogenated DBPs
      (trichloromethane, dichloroacetonitrile, and trichloronitromethane) and one non
      halogenated DBP (N-nitrosodimethylamine [NDMA]). Halogenated DBP yields were
      greater during the application of free chlorine, however chloramination produced
      significant levels of halogenated N-DBPs for some isolates. NDMA was only
      observed to form from selected nitrogen-enriched isolates (DOC/DON ratio < 20
      mg/mg), especially those isolated from treated wastewater. Other results
      indicated that nitrogen-enriched DOM resulted in increased yields of the other N
      DBPs studied.

PMID- 19587412
TI  - Sorption behavior of a synthetic antioxidant, polycyclic musk, and an
      organophosphate insecticide in wastewater sludge.
AB  - Emerging contaminants (ECs) are chemicals that are currently unregulated due to
      limited understanding of health effects and limited data regarding occurrence.
      Wastewater treatment plants (WWTP) receive many ECs as components of influent
      waste and the removal of organic contaminants, such as ECs, occurs primarily by
      sorption to sludge. Therefore, it is important to develop measures of sorption
      behavior by ECs to sludge. This study evaluates sorption of three ECs: 3-tert
      butyl-4-hydroxyanisole (BHA) a synthetic antioxidant, 1,3,4,6,7,8-hexahydro
      4,6,6,7,8,8-hexamethyl-cyclopenta(g)-2-benzopyrane (HHCB) a polycyclic musk, and
      chlorpyrifos a organophosphate insecticide. Twenty-four hour laboratory-scale
      sorption experiments were conducted for each compound individually and then in
      combination, which allowed the quantification of sorption onto wastewater sludge
      and the affects of multiple compounds. ECs in both the liquid and solid phases
      were analyzed using a gas chromatograph with flame ionization detector (GC/FID).
      Isotherms of individual sorption behavior followed a linear trend (R2 > 0.9) for
      individual ECs, while K(d) averaged 2,689 L kg(-1), 27,786 L kg(-1) and 31,402 L
      kg(-1) for BHA, chlorpyrifos and HHCB, respectively. Sorption behavior for BHA
      was linear during combined studies with K(d) of 1,766 L kg(-1) or a decrease of
      34%, while HHCB and chlorpyrifos followed non-linear isotherm models. Synergistic
      effects were observed with spike concentrations > or =25 mg L(-1) for HHCB and >
      or =20 mg L(-1) for chlorpyrifos. K(d) values ranged from 16,984-6,000,000 L kg(
      1) for HHCB and 19,536-3,000,000 L kg(-1) for chlorpyrifos. These distribution
      coefficients differed substantially from previously published values, mainly
      because few studies used sludge as the sorption media. Results suggest that HHCB
      and chlorpyrifos may be contained in the sludge unlike BHA, which is more
      available in the aqueous phase. Future investigations should evaluate WWTP
      processes for degrading ECs to harmless products and releases of ECs from sludge.

PMID- 19587413
TI  - Reducing the natural color of membrane bioreactor permeate with activated carbon
      or ozone.
AB  - The suitability of two membrane bioreactors for on-site wastewater treatment and
      reuse in Switzerland was investigated. The treated wastewater was used for toilet
      flushing and gardening, with water recycling rates of 30% (single family house)
      and almost 100% (toilets in a cable car station) respectively. Due to the
      recycling, an increase in a natural yellowish-brown color was observed, leading
      to double flushing of the toilets, higher cleaning requirements and increased
      permeate production. Color removal with ozone, powdered (PAC) and granulated
      (GAC) activated carbon was assessed in laboratory and field experiments. PAC was
      added directly into the MBR, whereas ozonation and GAC were applied to the
      permeate. The dosage of ozone or activated carbon depended on the recycling rate
      and color intensity. If color removal is necessary, PAC is the option best suited
      to small treatment plants, with a requirement of 30-50 g m(-3) for 30% and 100 g
      m(-3) for 100% water recycling.

PMID- 19587414
TI  - Oxidation reduction potential automatic control potential of intermittently
      aerated membrane bioreactor for nitrification and denitrification.
AB  - An intermittently aerated membrane bioreactor (IAMBR) process is designed to
      achieve greater removal efficiency of organic matter and nutrients than a regular
      membrane bioreactor (MBR) through the control on and off of an aerator. In this
      paper, we have investigated Oxidation/Reduction Potential (ORP) and Dissolved
      Oxygen (DO) values compared to NH4(+)-N and NO3(-)-N concentrations at SRTs of
      20, 30 and 40 days and C/N ratios of 4.5, 7, and 10. Additionally, the paper
      addresses a comprehensive approach to evaluate ORP as an appropriate factor for
      the auto-control of IAMBR process on the nitrification and denitrification and
      present DeltaORP/Deltat curve to confirm accurate completion time of aeration on
      and off. As the results of ORP and DO curve, it is proven that points of ORP
      bending and knee are appropriate factors for auto-control of the process in both
      aeration on and off time and ORP as well as DO relate to the dynamic behavior of
      nutrient concentration during a cycle. A peak point at aerobic state and a slump
      point at anoxic state on DeltaORP/Deltat curve obviously present the ORP bending
      point. Hence, it could find that peak point and slump point indicated the
      relatively accurate completion time of nitrification and denitrification
      respectively in IAMBR.

PMID- 19587415
TI  - Improved radar data processing algorithms for quantitative rainfall estimation in
      real time.
AB  - This paper describes a new methodology to process C-band radar data for direct
      use as rainfall input to hydrologic and hydrodynamic models and in real time
      control of urban drainage systems. In contrast to the adjustment of radar data
      with the help of rain gauges, the new approach accounts for the microphysical
      properties of current rainfall. In a first step radar data are corrected for
      attenuation. This phenomenon has been identified as the main cause for the
      general underestimation of radar rainfall. Systematic variation of the
      attenuation coefficients within predefined bounds allows robust reflectivity
      profiling. Secondly, event specific R-Z relations are applied to the corrected
      radar reflectivity data in order to generate quantitative reliable radar rainfall
      estimates. The results of the methodology are validated by a network of 37 rain
      gauges located in the Emscher and Lippe river basins. Finally, the relevance of
      the correction methodology for radar rainfall forecasts is demonstrated. It has
      become clearly obvious, that the new methodology significantly improves the radar
      rainfall estimation and rainfall forecasts. The algorithms are applicable in real
      time.

PMID- 19587416
TI  - Stormwater infiltration trenches: a conceptual modelling approach.
AB  - In recent years, limitations linked to traditional urban drainage schemes have
      been pointed out and new approaches are developing introducing more natural
      methods for retaining and/or disposing of stormwater. These mitigation measures
      are generally called Best Management Practices or Sustainable Urban Drainage
      System and they include practices such as infiltration and storage tanks in order
      to reduce the peak flow and retain part of the polluting components. The
      introduction of such practices in urban drainage systems entails an upgrade of
      existing modelling frameworks in order to evaluate their efficiency in mitigating
      the impact of urban drainage systems on receiving water bodies. While storage
      tank modelling approaches are quite well documented in literature, some gaps are
      still present about infiltration facilities mainly dependent on the complexity of
      the involved physical processes. In this study, a simplified conceptual modelling
      approach for the simulation of the infiltration trenches is presented. The model
      enables to assess the performance of infiltration trenches. The main goal is to
      develop a model that can be employed for the assessment of the mitigation
      efficiency of infiltration trenches in an integrated urban drainage context.
      Particular care was given to the simulation of infiltration structures
      considering the performance reduction due to clogging phenomena. The proposed
      model has been compared with other simplified modelling approaches and with a
      physically based model adopted as benchmark. The model performed better compared
      to other approaches considering both unclogged facilities and the effect of
      clogging. On the basis of a long-term simulation of six years of rain data, the
      performance and the effectiveness of an infiltration trench measure are assessed.
      The study confirmed the important role played by the clogging phenomenon on such
      infiltration structures.

PMID- 19587417
TI  - Ammonium removal from anaerobic digester effluent by ion exchange.
AB  - The effluent of a 500 kW biogas plant is treated with a solid separation, a micro
      filtration and a reverse osmosis to achieve nutrient recovery and an effluent
      quality which should meet disposal quality into public water bodies. After the
      reverse osmosis, the ammonium concentration is still high (NH(4)-N = 467 mg/l),
      amongst other cations (K+ = 85 mg/l; Na+ = 67 mg/l; Mg2+ = 0.74 mg/l; Ca2+= 1.79
      mg/l). The aim of this study was to remove this ammonium by ion exchange. Acidic
      gel cation exchange resins and clinoptilolite were tested in column experiments
      to evaluate their capacity, flow rates and pH. Amberjet 1,500 H was the most
      efficient resin, 57 BV of the substrate could be treated, 1.97 mol NH4-N/l resin
      were removed. The ammonium removal was more than 99% and the quality of the
      effluent was very satisfactory (NH4-N < 2 mg/l). The breakthrough of the observed
      parameters happened suddenly, the order was sodium-pH-ammonium-potassium. The
      sharp increase of the pH facilitates the online control, while the change in
      conductivity is less significant. A regeneration with 3 bed volumes of 2 M HCl
      recovered 91.7% of the original cation exchange capacity.

PMID- 19587418
TI  - Ferric coagulant recovered from coagulation sludge and its recycle in chemically
      enhanced primary treatment.
AB  - An investigation was conducted to study the feasibility of ferric coagulant
      recovery from chemical sludge and its recycle in chemically enhanced primary
      treatment (CEPT) to make the process more cost-effective, as well as reduce
      sludge volume. The optimum conditions and efficiency of the acidification for
      ferric coagulant recovery from coagulation sludge were investigated. Experimental
      results showed that the recovered coagulants can be used in CEPT and the
      pollutants removal efficiency is similar to that of fresh coagulant, and for some
      aspects the effect of recovered coagulants is better than that of fresh ones,
      such as turbidity removal. Although some substances will be enriched during
      recycle, they have little effect on treated wastewater quality. Acidification
      condition also had significant influence on reduction of sludge volume. The
      efficiency of coagulant recovery had a linear relationship with sludge reduction.
      Experiments verify that it would be a sustainable and cost-effective way to
      recover ferric coagulant from coagulation sludge in water treatment and chemical
      wastewater treatment, and then recycle it to CEPT, as well as reduce sludge
      volume.

PMID- 19587419
TI  - Evidence of traffic-related pollutant control in soil-based sustainable urban
      drainage systems (SUDS).
AB  - SUDS are being increasingly employed to control highway runoff and have the
      potential to protect groundwater and surface water quality by minimising the
      risks of both point and diffuse sources of pollution. While these systems are
      effective at retaining polluted solids by filtration and sedimentation processes,
      less is known of the detail of pollutant behaviour within SUDS structures. This
      paper reports on investigations carried out as part of a co-ordinated programme
      of controlled studies and field measurements at soft-engineered SUDS undertaken
      in the UK, observing the accumulation and behaviour of traffic-related heavy
      metals, oil and PAHs. The field data presented were collected from two extended
      detention basins serving the M74 motorway in the south-west of Scotland.
      Additional data were supplied from an experimental lysimeter soil core leaching
      study. Results show that basin design influences pollutant accumulation and
      behaviour in the basins. Management and/or control strategies are discussed for
      reducing the impact of traffic-related pollutants on the aqueous environment.

PMID- 19587420
TI  - Including public perception data in the evaluation of the consequences of
      sewerage derived urban flooding.
AB  - This text reports research which was undertaken to assess the failure
      consequences associated with sewerage systems. In an effort to move away from
      considering only flood volume, depth or extent, the text will focus on how a
      survey of public opinion was used to inform the development of a consequence
      scoring methodology. The failure consequences considered range from internal
      flooding of properties, to road closure, environmental damage and odour problems.
      The text reports the extent to which experience of flooding influences
      perceptions of failure consequence and sewerage system management. It is also
      outlined how this data was used, along with other data sources, to construct an
      objective scoring process that can be used to evaluate failure consequence and
      readily prioritise sewerage maintenance.

PMID- 19587421
TI  - Evaluation of different pre-hydrolysis times and enzyme pool concentrations on
      the biodegradability of poultry slaughterhouse wastewater with a high fat
      content.
AB  - The effect of different hydrolysis times (4, 8 and 24 h) of a lipase-rich
      enzymatic preparation (0.1, 0.5 and 1.0% w/v) produced by fungus Penicillium sp.
      in solid-state fermentation was evaluated on the anaerobic biodegradability of a
      poultry slaughterhouse wastewater with 800 mg oil and grease [O&G]/L in three
      sequential batches. The enzymatic pre-treatment of O&G in the experiments with no
      acclimated sludge had no discernible effect because regardless of the conditions
      adopted COD removal efficiencies of 95.3% to 98.7% were obtained. However, when
      the sludge was reused (once or twice) the COD removal efficiencies in the control
      experiments (69.8% and 53.4%) were considerably lower than in the experiments
      with hydrolyzed effluent (of 93.8% to 98.4%). Higher values of specific methane
      production were obtained with 0.1% SEP and 4 h of hydrolysis. After acclimation
      of the sludge, 19.9% fat was still adhered to the sludge in the control
      experiment, while the sludge in the experiment with enzymatically pre-treated
      effluent contained only 8.6% fat, confirming the accumulation of fat when the
      enzyme pool was not used.

PMID- 19587422
TI  - Capillary nanofiltration coupled with powdered activated carbon adsorption for
      high quality water reuse.
AB  - Direct capillary nanofiltration was tested for reclamation of tertiary effluent
      from a municipal wastewater treatment plant. This process can be regarded as a
      promising treatment alternative for high quality water reuse applications when
      combined with powdered activated carbon for enhanced removal of organic
      compounds. The nanofiltration was operated at flux levels between 20 and 25 L/(m2
      h) at a transmembrane pressure difference of 2-3 bar for approximately 4,000
      operating hours. The study was conducted with PAC doses in the range from 0 to 50
      mg/L. The plant removal for DOC ranged from 88-98%. The sulfate retention of the
      membrane filtration process was between 87 and 96%. The process provided a
      consistently high permeate quality with respect to organic and inorganic key
      parameters.

PMID- 19587423
TI  - Evaluation of enterococcal surface protein genes as markers of sewage
      contamination in tropical recreational waters.
AB  - A molecular monitoring strategy was developed to detect prevalence of two
      enterococcal surface protein genes (esp-1 gene and esp-2 gene) in isolates of
      enterococci from recreational waters in Hawaii as evidence of human sewage
      contamination. The sensitivity and specificity of the methods were evaluated in
      selected environmental samples including human sewage, ocean water samples near a
      sewage outfall, shoreline coastal beach waters, ambient soil samples and ambient
      streams not known to be contaminated with sewage. The results of this study show
      that the esp-1 and esp-2 genes are highly associated with enterococci from sewage
      sources as compared to non-point sources. Therefore these esp genes show promise
      as good indicators of sewage contamination. However, more sensitivity and
      specificity of esp genes are needed. Moreover, a more specific enumeration method
      for E. faecium and E. faecalis is needed so that subsequent test for the esp
      genes will be reliable and feasible.

PMID- 19587425
TI  - Effect of CpG motif containing oligodeoxynucleotides on dendritic cell function
      in patients with chronic hepatitis B.
AB  - OBJECTIVE: To explore the effect of unmethylated CpG motif containing
      oligodeoxynucleotides (CpG ODN) on the function of dendritic cells (DCs) in
      patients with chronic hepatitis B (CHB). METHODS: DCs were obtained from
      peripheral blood mononuclear cells (PBMCs) of 15 CHB patients, 12 hepatitis B
      virus (HBV) carriers, and 10 healthy controls. The expressions of HLA-DR, CD80,
      and CD86 on DCs were determined by fluorescence activated cell sorting (FACS).
      The IL-12 level in supernatant of the culture medium was measured by ELISA, and
      the morphological changes of DCs were observed under transmission electron
      microscope. RESULTS: Compared with the controls, DCs stimulated with CpG ODN
      represented enrichment in cell surface protrusions and rough endoplasmic
      reticulum, decreased or disappeared vacuole. The expressions of HLA-DR, CD86, and
      CD80 were much higher in DCs stimulated with CpG ODN than those in complete
      medium control (P<0.05). When culturing in complete medium, the expressions of
      HLA-DR, CD86, and CD80 were much lower in CHB patients and HBV carriers than
      healthy controls (P<0.05). The expressions of HLA-DR and CD86 stimulated with CpG
      ODN were much lower in CHB patients than HBV carriers and healthy controls
      (P<0.05). The expressions of CD80 were much lower in CHB patients and HBV
      carriers than healthy controls (P<0.05). The levels of IL-12 were much higher in
      DCs stimulated with CpG ODN than that in complete medium controls (P<0.05). The
      levels of IL-12 in complete medium or medium added with CpG ODN were much lower
      in CHB patients and HBV carriers than in healthy controls (P<0.05). CONCLUSION:
      CpG ODN could significantly promote the maturation of dendritic cells in
      peripheral blood in CHB patients.

PMID- 19587424
TI  - Evaluation of the anaerobic degradation of black liquor from a Kraft pulp plant
      with addition of organic co-substrates.
AB  - The purpose of this study was to assess the anaerobic degradation of black liquor
      with and without additional carbon sources. Batch experiments were conducted
      using black liquor, from an integrated pulp and paper mill adding ethanol,
      methanol and nutrients. The PCR/DGGE technique was used to characterize the
      structure of the microbial community. The addition of extra sources of carbon did
      not significantly influence the degradation of black liquor under the conditions
      evaluated and the microbial community was similar in all experiments. It was
      observed an increase in some members of the archaeal in reactors that had the
      best efficiencies for removal of black liquor (around 7.5%). Either ethanol or
      methanol can be used as co-substrates because the produce the same quantitative
      and qualitative effect.

PMID- 19587426
TI  - Effect of early hyperbaric oxygen on neuronal apoptosis and learning and memory
      of cerebral ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: To explore the effect of early hyperbaric oxygen (HBO) on neuronal
      apoptosis and learning and memory in rats treated with cerebral ischemia
      reperfusion injury in 30 min. METHODS: Experimental rats were randomly divided
      into 3 groups: a sham-operation group, a model group, and a treatment group.
      Cerebral ischemia-reperfusion injury model was induced by Zea Longa's method.
      Neurologic impairment score, apoptosis cell, and the expression of caspase-3 and
      Bcl-2 protein were observed. The amount across platform and the escape latency
      (EL) time were determined by Morris water maze. RESULTS: Neurologic impairment
      scores at 2 h, 1 d, 2 d, and 3 d of the model group and the treatment group were
      obviously higher than the sham-operation group (P<0.01), and those at 2 d and 3 d
      of the treatment group were obviously lower than those of the model group
      (P<0.05). The number of apoptosis cells and the expression of caspase-3 protein
      in the model group significantly increased compared with those in the sham
      operation group (P<0.01), while those in the treatment group was significantly
      lower than the model group (P<0.01). Bcl-2 protein expression in the model group
      increased more obviously than that in the sham-operation group (P<0.01), and that
      in the treatment group was much higher than the model group (P<0.01). The EL time
      of the model group was much longer than that of the sham-operation group and the
      number across platform was obviously decreased compared with that of the sham
      operation group (P<0.01), while the EL time of the treatment group was much
      shorter than that of the model group and the number across platform was more than
      that of the model group (P<0.05). CONCLUSION: Early hyperbaric oxygen could
      inhibit nerve cell apoptosis suffered cerebral ischemia-reperfusion injury and
      improve the function of learning and memory.

PMID- 19587427
TI  - Surgical management of infected pseudoaneurysms of femoral artery caused by
      narcotics injection.
AB  - OBJECTIVE: To investigate the surgical management of infected pseudoaneurysms of
      femoral artery caused by narcotics injection. METHODS: The clinical data of 63
      cases of infected pseudoaneurysms of femoral artery caused by narcotics injection
      were reviewed retrospectively. RESULTS: The tumors in 52 cases ruptured. Rupture
      hemorrhoea first occurred in 45 patients before admission and in 7 during
      hospitalization. Twenty-six patients suffered from recurrent or multiple
      hemorrhoea while in hospital. Forty-nine patients received external iliac artery
      superficial femoral artery extra-anatomic bypass reconstruction with banded
      vascular grafts and the other 14 received ligation operations of the external
      iliac artery or the femoral artery. No one died in the perioperative period. One
      patient with vascular graft reconstruction developed graft infection during
      hospitalization and 5 developed graft infection during the follow-up. No ischemic
      necrosis occurred in the affected limbs after the infected vascular grafts were
      removed. One patient developed necrosis in the affected limb after the femoral
      artery was ligated and then above-knee amputation was performed. The others
      recovered well. Unobstructed blood circulation in the vascular graft was
      exhibited by color Doppler ultrasonography in 36 cases during the follow-up.
      CONCLUSION: Operation as early as possible is the only way to rescue patients'
      lives threatened by infected pseudoaneurysms of femoral artery caused by
      narcotics injection. Thorough debridement and drainage, revascularization between
      external iliac artery and superficial femoral artery using band artificial blood
      vessel, and controlling infection are therapeutic modus operandi. Ligation of
      external iliac artery or femoral artery is also a feasible measure to rescue
      patients' lives when pseudoaneurysms are infected severely.

PMID- 19587428
TI  - [Establishment of protein expression profile of laser capture microdissection
      purified nasopharyngeal carcinoma tissue].
AB  - OBJECTIVE: To establish the protein expression map of nasopharyngeal carcinoma
      (NPC), and provide a basis for proteomic study of NPC. METHODS: Laser capture
      microdissection (LCM) was used to isolate cancer cells from NPC tissues. Two
      dimensional gel electrophoresis(2-DE) was used to separate the total proteins of
      LCM purified NPC cells. Matrix-assisted laser desorption/ionization-time of
      flight-mass spectrometry (MALDI-TOF-MS) was performed to identify the proteins,
      and bioinformatics was used to construct the 2-DE database of NPC proteome.
      RESULTS: A 2-DE reference map of NPC was established. On the 2-DE map, a total of
      (1 312+/-30) protein spots were detected, and 427 protein spots representing 241
      non-redundant proteins were identified. The 2-DE database of NPC proteome was
      constructed. These data could be accessed at our website
      (http://www.xyproteomics.org). CONCLUSION: A protein expression profile of LCM
      purified NPC tissues has been established for the first time, which provides
      useful information and source for proteomic study of NPC.

PMID- 19587429
TI  - [Hemodynamic characteristics of chronic congestive heart failure model in awake
      Beagle dogs].
AB  - OBJECTIVE: To characterize the hemodynamic changes of chronic congestive heart
      failure(CHF) model induced by rapid right ventricular pacing after myocardial
      infarction in awake Beagle dogs. METHODS: Five healthy adult male Beagle dogs
      were prepared for surgery. After the probes for measurement and the pacing leads
      were implanted, the left anterior descending artery was ligated during the
      surgery to induce myocardial infarction in the anterior wall of the left
      ventricle close to the apex. Six weeks after the surgery, rapid right ventricular
      pacing was initiated at the rate of 220 to 260 beats per minute for 4 weeks to
      induce CHF. Echocardiography was performed before the surgery. Both
      echocardiography and hemodynamic measurement were carried out before the rapid
      pacing and 4 weeks after the rapid pacing when the Beagle dogs were awake.
      RESULTS: There was no significant difference in left ventricle end diastolic
      diameter (LVEDD), left ventricle ejective fraction (LVEF), and fractional
      shortening (FS) between pre-operation and pre-pacing. LVEDD [(44.71+/-3.35) vs.
      (38.01+/-1.54) mm] and left ventricle end diastolic pressure (LVEDP) [(25.63+/
      1.86) vs. (10.58+/-1.23) mmHg] at 4 weeks after pacing significantly increased
      compared with the pre-pacing data(P<0.05). LVEF, FS, and LV dp/dt max were
      significantly declined (P<0.01). CONCLUSION: Left ventricle remodeling and
      hemodynamic changes in the Beagle dog CHF models produced by rapid right
      ventricular pacing after myocardial infarction are similar to the changes
      observed in CHF of human beings.

PMID- 19587430
TI  - [Role of Notch signaling in differentiation of retinal progenitor cells].
AB  - OBJECTIVE: To investigate the role of Notch signaling in differentiation of
      Sprague-Dawley (SD) rat retinal progenitor cells (RPCs). METHODS: RPCs were
      isolated from 16-day embryonic SD rats and cultured in suspension. RPCs were
      cultured respectively in media with (treatment group) or without (control group)
      gamma-secretase inhibitor X which was used to block Notch signaling.
      Morphological observation and immunocytochemistry were applied at day 14 to
      determine the cell types and analyze the expression of Notch pathway genes in
      both groups. RESULTS: Most RPCs expressed Notch1 intracellular domains or its
      downstream transcriptional factor Hes1. A few expressed bHLH transcriptional
      factors NeuroD and Mash1. Most auto-differentiated RPCs expressed NeuroD or
      Mash1, while a few of them expressed Notch1 intracellular domains or Hes1. In the
      group treated with gamma-secretase inhibitor X, the positive rate of Nestin or
      GFAP was much lower than that in the control group while the positive rate of
      beta-tubulin was much higher than that in the control group. The difference in
      the positive rate of recovering between the two groups was not significant.
      CONCLUSION: In vitro Notch signaling may inhibit retinal stem cells
      differentiation. Inhibiting Notch signaling in vitro may promote differentiation
      to neurons and partially inhibit glial differentiation.

PMID- 19587431
TI  - [GJB2 (connexin 26) gene mutation screen in patients with nonsydromic hearing
      loss in Hunan].
AB  - OBJECTIVE: To identify the genetic characteristics in patients with nonsydromic
      hearing loss (NSHL) in Hunan province, to determine the prevalence and spectrum
      of mutations in GJB2 gene, and to explore the pathogenic mechanism. METHODS: A
      total of 140 sporadic patients with NSHL were enrolled after clinical
      examination. Molecular studies were performed by amplifing the coding region of
      GJB2 gene, purifying the PCR products, and sequencing directly. Sequences were
      analysed by DNAStar software to determine GJB2 mutations in the patients. Special
      method was designed to confirm the unreported mutation. RESULTS: We detected GJB2
      mutation in 56 out of the 140 patients (40%, 56/140). Both of the 2 alleles were
      mutated in 29 patients and 1 allele in the other 27 patients, and the rate of
      allele mutation was 30.4%(85/280). Ten variations were detected, including 7
      mutations and 3 polymorphisms. The deaf-causing mutations were nonsense mutation
      c.139G>T; frameshift mutation c.235delC and c.176-191del16; and missense mutation
      c.109G>A, c.344T>G, c.550C>T and c.571T>C. The unreported missense mutation was
      c.344T>G. The c.235delC mutation was the most prevalent mutation found in the 27
      patients (19.3%, 27/140). The frequency of c.109G>A mutation was next to
      c.235delC found in 25 patients (17.9%, 25/140). CONCLUSION: GJB2 mutation is a
      major cause for NSHL. The most common-spot in Chinese patients with NSHL is
      c.235delC. The unreported missense mutation is c.344T>G.

PMID- 19587432
TI  - [PTSD-positive screening and factors influencing the mental state in victims
      evacuated/ not evacuated from Wenchuan earthquake area within 1 month].
AB  - OBJECTIVE: To explore posttraumatic stress disorder (PTSD) positive screening and
      factors influencing the mental state in victims who were evacuated/were not
      evacuated from Wenchuan earthquake area within 1 month. METHODS: The 3 groups
      included 235 victims who were not evacuated from Shifang territory (the incident
      scene, Group A), 44 victims who were evacuated to Second Xiangya Hospital (the
      wounded, Group B) and 36 relatives (the relatives, Group C). The mental state of
      all subjects was evaluated by Impact of Event Scale-Revised (IES-R) and other
      tools. RESULTS: (1) One month after the disaster, and the positive rate of PTSD
      screening in these survivors was 35.56%, the positive rate in women was
      significantly higher than that in men (chi(2)=16.27,P<0.001). The positive rate
      of PTSD screening in Group A, Group B and Group C was 39.15%, 31.82%, and 16.67%,
      respectively, with significant difference (chi(2)(mh)=5.243,P<0.05). Among the
      three groups which met the diagnosis criterion of PTSD symptoms, the scores for
      "numbness/avoidance symptom"and "excessive arousing symptom"in Group A were
      significantly higher than those in Group B and C (P<0.01). (2) The scores for
      "anxiety"and "depression"and "psychosomatic"symptoms in Group A and Group B were
      significantly higher than those in Group C (P<0.05). (3) Gender, place of
      residence and evacuating from the earthquake area or not were factors of PTSD
      symptoms. CONCLUSION: One month after the earthquake, the victims suffered
      psychologically. PTSD symptoms, anxiety and depression symptoms were their major
      mental problems, more attention to especially women victims. The protection
      factors include dispersing victims to the secure place as soon as possible,
      expanding and strengthening society support. Early psychological interventions
      will help victims to raise their psychological endurance and prevent PTSD
      effectively.

PMID- 19587433
TI  - [Mutation analysis of neural cell adhesion molecules in human astrocytoma].
AB  - OBJECTIVE: To identify the function of neural cell adhesion molecule (NCAM)
      mutation in the genesis of human glioma. METHODS: Mutations were found through
      polymerase chain reaction-single strand conformation polymorphism, and then the
      changed DNA fragments were purified and multiplied and sent to Shanghai for
      sequencing. Blast and ORF finder were used to find out the amino changes in NCAM.
      RESULTS: An A-C transversion was found at position 1 126 in NCAM's 7 exon in a
      patient with glioblastoma from 43 astrocytoma. CONCLUSION: Structural change in
      the protein caused by point mutation may be the reason for tumorigenesis of
      astrocytoma.

PMID- 19587434
TI  - [Effect of arsenic trioxide combined with adriamycin on the proliferation and
      apoptosis of human lymphoma cells].
AB  - OBJECTIVE: To determine the effect of arsenic trioxide combined with
      adriamycin(ADM) on the proliferation and apoptosis of human lymphoma cells.
      METHODS: Raji cells were divided into an experimental group and a control group,
      and the experimental group was further divided into 1 micromol/L As(2)O(3)
      group,2 micromol/L As(2)O(3) group, ADM group,1 micromol/L As(2)O(3) and ADM
      group,2 micromol/L As(2)O(3) and ADM group. Human lymphoma cells Raji were
      treated with As(2)O(3) combined with ADM. Wright-Giemsa dying assay was used to
      observe the apoptosis morphology of lymphoma cells. The proliferation of the
      cells treated with As(2)O(3) and adriamycin was detected by the method of 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT). Flow cytometry(FCM)
      was used to detect the apoptosis rate of lymphoma and the fluorescene density in
      the lymphocytes. Effect of arsenic trioxide and adriamycin on the mutant p53
      expression in Raji cells was detected by semi-quantitive RT-PCR. RESULTS: Evident
      apoptotic morphological changes of Raji cells were observed 24 hours after
      treatment with As(2)O(3) or ADM. Compared with As(2)O(3) or ADM alone, As(2)O(3)
      combined with ADM could increase the inhibition ratio significantly (P<0.05), and
      the inhibition rate was related to the concentration and action time of As(2)O(3)
      (P<0.05). Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could
      increase the apoptosis rate of lymphoma cells with obvious difference (P<0.05).
      Semi-quantitive and RT-PCR showed that the expression of mutant p53 in As(2)O(3)
      and ADM alone and combined groups was obviously less than that in the control
      (P<0.05). After the treatment with 1 micromol/L and 2 micromol/L As(2)O(3), the
      fluorescene density in the Raji cells was 18.53 and 18.12, 0.056 and 0.023 times
      increase respectively.There was no difference (P>0.05). CONCLUSION: As(2)O(3) and
      ADM alone or combined can inhibit the proliferation, induce cell apoptosis, and
      downregulate the expression of mutant p53 in vitro. As(2)O(3) combined with ADM
      has synergistic anti-lymphoma cell effect in vitro. As(2)O(3) has no significant
      effect on the concentration of ADM on the Raji cells, but can enhance the
      chemosensitivity of Raji cells, and its mechanism may be that it can downregulate
      the expression of mutant p53.

PMID- 19587435
TI  - [Clinicopathologic features and diagnosis of 18 patients with angioimmunoblastic
      T-cell lymphoma].
AB  - OBJECTIVE: To explore the clinical and pathologic features of angioimmunoblastic
      T-cell lymphoma(AITL) and provide evidence for diagnosis. METHODS: Eighteen AITL
      patients (9 males and 9 females aged from 14 to 70 years) were retrospectively
      analyzed in Xiangya Hospital of Central South University from July 2002 to
      September 2007. RESULTS: Characteristic features at the presentation of AITL
      included generalized lymphadenopathy, fever, splenomegaly, and skin rashes with
      polyclonal hyper-gammaglobulinemia and other hematological abnormalities (such as
      Coombs-positive hemolytic anemia), which often involved the bone marrow and had
      well-described histologic features. The positive rate for CXCL13 was 93.3%.
      CONCLUSION: Repeated lymphadenbiopsy is helpful for AITL diagnosis. Routine
      histological and immunohistochemical examinations (especially including CXCL13)
      play significant role in the diagnosis and differential diagnosis of AITL.

PMID- 19587436
TI  - [Effect of neoadjuvant chemotherapy on cervical carcinoma].
AB  - OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on cervical
      carcinoma and its association with clinical data. METHODS: A total of 97 patients
      with stage Ib2 approximately IIIa of cervical cancinoma were treated with
      neoadjuvant chemotherapy. The effect of chemotherapy, factors associated with
      outcome of chemotherapy, and histology were analyzed. RESULTS: Effective rate of
      chemotherapy was 86.6% which was associated with clinical stage and histology.
      Eight-four patients received radical hysterectomy. The histological grade of 17
      patients was lowered, lymph nodes in 19 patients were positive, and 6 patients
      had parametrium invasion. One patient died within 1 year after the operation, and
      5 patients recurred. CONCLUSION: The effect of neoadjuvant chemotherapy for
      locally advanced cervical cancinoma is good. Surgery after chemotherapy can
      improve the prognosis and 5-year survival rate.

PMID- 19587437
TI  - [Expression of NMBR in myometrium in pregnant mice at different gestational ages
      and its relation with parturition].
AB  - OBJECTIVE: To investigate the spatiotemporal expression of neuromedin B receptor
      (NMBR) in mice myometrium at different pregnant stages, as well as its mechanism
      and relation with parturition. METHODS: The pregnant mice were divided into no
      pregnancy (NP), early pregnancy (EP), mid-pregnancy (MP), late-pregnancy (LP),
      parturition (PT) and postpartum (PP) groups (12 mice in each group), according to
      pregnant stage. The mRNA and protein expression of NMBR, HSP70 and IL-6 were
      detected in myometrium in pregnant mice by semi-quantitative RT-PCR and Western
      blot, while NF-kappaB-P65 DNA binding activity was determined by NoShift
      transcription factor assay kits, respectively. Their relation with parturition
      was analyzed. RESULTS: The mRNA expression level of NMBR in the PT group was
      significantly higher than that in the NP, EP, LP and PP groups (P<0.05), but this
      difference was not observed in the MP group (P>0.05). The NMBR protein in PT
      group was significantly higher than that in the other 5 groups (P<0.01). NF
      kappaB-P65 DNA binding activity at PT group was remarkably higher than that in
      the NP, LP and PP groups (P<0.05). The expression of IL-6 mRNA was significantly
      higher than that in the NP, LP and PP groups (P<0.05), its protein expression in
      PT and LP groups was significantly higher than that in the NP and PP groups
      (P<0.05). The expression of HSP70 mRNA in the PT group was significantly higher
      than that in the NP and PP groups (P<0.05), and the protein of HSP70 was
      significantly up-regulated in PT and PP groups compared with in NP and LP groups
      (P<0.05). The DNA-binding activity of P65 was positively correlated to the mRNA
      expression of NMBR and IL-6 (r=0.40, P<0.01; r=0.30, P<0.05), so were positively
      correlated to DNA-binding activity of P65, mRNA expression of HSP70 and NMBR (
      r=0.40, P<0.01; r=0.49, P<0.01). DNA-binding activity of P65 did not correlate
      with the mRNA expression of HSP70. CONCLUSION: The mRNA and protein expressions
      of NMBR reach a peak at the onset of labor. NMBR may play an important role in
      the parturition via NF-kappaB P65-IL-6 signal transduction pathway. It may also
      influence the onset of labor by regulating HSP70, but this role does not rely on
      P65 pathway.

PMID- 19587438
TI  - [Identification of active efflux system gene qacA/B in methicillin-resistant
      Staphylococcus aureus and its significance].
AB  - OBJECTIVE: To detect the active efflux gene qac gene in methicillin-resistant
      Staphylococcus aureus (MRSA) by hem-nested polymerase chain reaction (PCR) and to
      learn the carrier condition of qac gene. METHODS: The active efflux gene qacA/B
      and qacB of 80 strains MRSA isolated from clinical specimens from Aug 2006 to
      March 2008 were amplified in vitro by hem-nested PCR with the primers designed by
      computers based on qac information of Genbank, and the PCR fragments were
      sequenced and analyzed. RESULTS: We detected qacA/B in 19 out of the 80 MRSA
      strains (23.75%) and qacB in 18 out of the 80 MRSA strains (22.5%). Compared with
      sequences of qacA (NO.X56628) and qacB(NO.AF535087) in the Genbank, 98% and 97%
      were identical, respectively. CONCLUSION: The active efflux gene qac gene in MRSA
      is detected by hem-nested PCR. The proportion of qac gene positive strains is
      high in clinical practice, which is related to its multi-antibiotic resistance.

PMID- 19587439
TI  - [Characteristics of spectra of superior vena cava flow Doppler velocities in
      pulmonary arterial hypertension].
AB  - OBJECTIVE: To explore and evaluate the characteristics of spectra wave shapes and
      parameters of the superior vena cava (SVC) Doppler flow patterns in patients with
      pulmonary arterial hypertension(PAH) by echocardiography. METHODS: Forty-nine
      patients with PAH as the PAH group and the paired healthy subjects as the control
      group were included in this study. Transthoracic echocardiography was used, and
      the spectra of SVC flow Doppler velocities in the right supraclavicular fossa
      view were examined and recorded. Peak velocity and velocity time integral (VTI)
      were measured. RESULTS: The spectra wave shapes of SVC flow velocity in the PAH
      group were distinguished from those of the control. The peak velocity and VTI of
      S waves during inspiration and the rate of respiratory changes of peak velocity
      of SVC flow Doppler velocity in moderate and severe PAH groups were significantly
      lower than those of the control (P<0.05).The peak velocity and VTI of D waves of
      SVC flow Doppler velocity in the PAH groups were significantly lower than those
      of the control (P<0.05). The rate of respiratory changes of peak velocity of D
      waves in the PAH groups was significantly lower than those of the control
      (P<0.05). The peak velocity and VTI of AR, and VR waves of SVC flow Doppler
      velocity in the PAH groups were significantly higher than those of the control
      (P<0.05). Linear regression analysis revealed a significant correlation between
      pulmonary arterial systolic pressure(PASP) and the Vexp/Vins ratio (r=0.760,
      P<0.001). CONCLUSION: The spectra wave shapes of SVC flow velocity in the PAH
      groups were distinguished from those of the control which may have some
      diagnostic value for PAH.The peak velocities and VTI of S waves during
      inspiration, D waves, AR waves and VR waves of SVC flow Doppler in the PAH groups
      are different from the control. The ratio of Vexp/Vins of S wave may be a non
      invasive quantitative index to detect PAH.

PMID- 19587440
TI  - [Effect of Tongxinluo on endothelial function and hypersensitive C-reactive
      protein in acute coronary syndrome patients undergoing percutaneous coronary
      intervention].
AB  - OBJECTIVE: To determine the effect of Tongxinluo on the endothelial function and
      hypersensitive C-reactive protein (hs-CRP) in acute coronary syndrome patients
      undergoing percutaneous coronary intervention(PCI). METHODS: Thirty-three
      patients with unstable angina pectoris and 6 patients with acute myocardial
      infarction who underwent PCI for stenotic lesions of the coronary artery were
      enrolled. The patients were randomly assigned to a conventional group (n = 19)
      which took routine treatment or a tongxinluo group (n = 20) which took
      Tongxinluo(4 capsules once, 3 times per day) at the base of routine treatment
      after PCI. Nitric oxide synthase (NOS), nitric oxide (NO), endothelium-dependent
      vasodilation which was evaluated in the brachial artery flow mediated
      diameter(FMD) and hs-CRP were measured before the PCI and 24 hours and 3 months
      after the PCI. The correlation between NO and hs-CRP was analyzed. RESULTS: NOS,
      NO, and FMD in the 2 groups 24 hours after the PCI were significantly lower than
      those before the PCI(P < 0.05), but hs- CRP obviously increased (P < 0.05). NOS,
      NO, and FMD 3 months after the PCI in the 2 groups were significantly higher than
      those before the PCI (P < 0.05 or P < 0.01), but hs-CRP obviously decreased (P <
      0.01).All indexes mentioned above in the Tongxinluo group showed greater changes
      than those of the conventional group(P < 0.05). NO was negatively correlated with
      hs-CRP (r = -0.3219, P<0.01). CONCLUSION: Tongxinluo capsules have obvious
      beneficial effect on endothelial function and anti-inflammation in acute coronary
      syndrome patients undergoing PCI, by directly acting on the endothelium and
      indirectly inhibiting inflammation.

PMID- 19587441
TI  - [Immunoregulatory effect of Huangqi Fuzhengtang on immunosuppressive mice].
AB  - OBJECTIVE: To explore the immunoregulatory effect of Huangqi Fuzhengtang on
      immunosuppressive mice. METHODS: The immunosuppressive mouse model was
      established by using hydrocortisone. Huangqi Fuzhengtang and Yupingfeng San
      apozema were given to the mice intragastrically. The contents of hemolysin, IL-2,
      and INF-gamma in the mouse serum and the expression of CD3(+), CD4(+), and CD8(+)
      in the peripheral blood lymphocytes were measured. RESULTS: Huangqi Fuzhengtang
      could obviously elevate the contents of hemolysin, IL-2, INF-gamma and the ratio
      of CD4(+) and CD8+, which was more effective than Yupingfeng San. CONCLUSION:
      Huangqi Fuzhengtang could improve the immune function in the immunosuppressive
      mice.

PMID- 19587442
TI  - [Serum adiponectin, leptin level, and bone mineral density in postmenopausal
      women].
AB  - OBJECTIVE: To determine whether serum adipocytokines and leptin level are
      associated with bone mineral density (BMD) in postmenopausal women. METHODS:
      Serum adiponectin and leptin level were measured by ELISA in 336 postmenopausal
      women. BMD was measured by dual energy X-ray absorptiometry (DXA) at the whole
      body, lumbar spine, hip, and forearm. Body compositions including lean tissue
      mass and body fat mass were measured by DXA, and their relationship was analyzed.
      RESULTS: Serum adiponectin levels were negatively related to BMD at the whole
      body, the lumbar spine, the hip, and the forearm (r = -0.181, r = -0.208, r = 
      0.228, r = -0.203, and P < 0.05, respectively). After adjustment for age and fat
      mass, the correlation with BMD still remained (r = -0.131, r = -0.140, r = 
      0.159, r = -0.172, and P<0.05, respectively). Serum leptin levels were positively
      related to BMD was at the hip and the forearm (r = 0.162, r = 0.210, and P <
      0.05, respectively). After adjustment for age and fat mass, the correlation with
      BMD at the forearm remained (r = 0.157, P<0.05), but the correlation with BMD at
      the hip disappeared. In the multiple linear stepwise regression analysis, year
      since menopause, lean mass, adiponectin, and estradiol were independent
      predictors of BMD at the body, the hip and the forearm; year since menopause,
      lean mass, body mass index, adiponectin, and extradiol were independent
      predictors of BMD at the lumbar spine. CONCLUSION: Adiponectin is the independent
      predictor of BMD.

PMID- 19587443
TI  - [Effect of alendronate on glucocorticoid-induced osteoporosis].
AB  - OBJECTIVE: To determine the effect of alendronate on glucocorticoid-induced
      osteoporosis(GIO). METHODS: Thirty-five GIO patients were enrolled. Ten
      milligrams alendronate were prescribed daily for 6 months. Bone mineral density
      (BMD) was measured by dual-energy X-ray absorptiometer (DEXA) after and before
      the treatment. RESULTS: BMD at lumbar, neck and trochanter sites of the 35
      patients after the treatment was significantly increased compared with those
      before the treatment (P<0.05). Urine Ca/Cr level was decreased (P<0.05). There
      was no severe side effect. CONCLUSION: Alendronate is effective and well
      tolerated for GIO.

PMID- 19587444
TI  - [A case of aggressive angiomyxoma in maxillary sinus].

PMID- 19587445
TI  - CSF-1 signals directly to renal tubular epithelial cells to mediate repair in
      mice.
AB  - Tubular damage following ischemic renal injury is often reversible, and tubular
      epithelial cell (TEC) proliferation is a hallmark of tubular repair. Macrophages
      have been implicated in tissue repair, and CSF-1, the principal macrophage growth
      factor, is expressed by TECs. We therefore tested the hypothesis that CSF-1 is
      central to tubular repair using an acute renal injury and repair model,
      ischemia/reperfusion (I/R). Mice injected with CSF-1 following I/R exhibited
      hastened healing, as evidenced by decreased tubular pathology, reduced fibrosis,
      and improved renal function. Notably, CSF-1 treatment increased TEC proliferation
      and reduced TEC apoptosis. Moreover, administration of a CSF-1 receptor-specific
      (CSF-1R-specific) antibody after I/R increased tubular pathology and fibrosis,
      suppressed TEC proliferation, and heightened TEC apoptosis. To determine the
      contribution of macrophages to CSF-1-dependent renal repair, we assessed the
      effect of CSF-1 on I/R in mice in which CD11b+ cells were genetically ablated and
      determined that macrophages only partially accounted for CSF-1-dependent tubular
      repair. We found that TECs expressed the CSF-1R and that this receptor was
      upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and
      humans. Furthermore, signaling via the CSF-1R stimulated proliferation and
      reduced apoptosis in human and mouse TECs. Taken together, these data suggest
      that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and
      direct autocrine/paracrine action on TECs.

PMID- 19587446
TI  - Focal adhesion kinase is required for neural crest cell morphogenesis during
      mouse cardiovascular development.
AB  - Neural crest cells (NCCs) participate in the remodeling of the cardiac outflow
      tract and pharyngeal arch arteries during cardiovascular development. Focal
      adhesion kinase (FAK) mediates signal transduction by integrin and growth factor
      receptors, each of which is important for normal cardiovascular development. To
      investigate the role of FAK in NCC morphogenesis, we deleted it in murine NCCs
      using Wnt1cre, yielding craniofacial and cardiovascular malformations resembling
      those observed in individuals with DiGeorge syndrome. In these mice, we observed
      normal cardiac NCC migration but reduced differentiation into smooth muscle
      within the aortic arch arteries and impaired cardiac outflow tract rotation,
      which resulted in a dextroposed aortic root. Moreover, within the conotruncal
      cushions, Fak-deficient NCCs formed a less organized mesenchyme, with reduced
      expression of perlecan and semaphorin 3C, and exhibited disorganized F-actin
      stress fibers within the aorticopulmonary septum. Additionally, absence of Fak
      resulted in reduced in vivo phosphorylation of Crkl and Erk1/2, components of a
      signaling pathway essential for NCC development. Consistent with this, both TGF
      beta and FGF induced FAK and Crkl phosphorylation in control but not Fak
      deficient NCCs in vitro. Our results indicate that FAK plays an essential role in
      cardiac outflow tract development by promoting the activation of molecules such
      as Crkl and Erk1/2.

PMID- 19587447
TI  - The circadian clock protein Period 1 regulates expression of the renal epithelial
      sodium channel in mice.
AB  - The mineralocorticoid aldosterone is a major regulator of sodium transport in
      target epithelia and contributes to the control of blood pressure and cardiac
      function. It specifically functions to increase renal absorption of sodium from
      tubular fluid via regulation of the alpha subunit of the epithelial sodium
      channel (alphaENaC). We previously used microarray technology to identify the
      immediate transcriptional targets of aldosterone in a mouse inner medullary
      collecting duct cell line and found that the transcript induced to the greatest
      extent was the circadian clock gene Period 1. Here, we investigated the role of
      Period 1 in mediating the downstream effects of aldosterone in renal cells.
      Aldosterone treatment stimulated expression of Period 1 (Per1) mRNA in renal
      collecting duct cell lines and in the rodent kidney. RNA silencing of Period 1
      dramatically decreased expression of mRNA encoding alphaENaC in the presence or
      absence of aldosterone. Furthermore, expression of alphaENaC-encoding mRNA was
      attenuated in the renal medulla of mice with disruption of the Per1 gene, and
      these mice exhibited increased urinary sodium excretion. Renal alphaENaC-encoding
      mRNA was expressed in an apparent circadian pattern, and this pattern was
      dramatically altered in mice lacking functional Period genes. These results
      suggest a role for Period 1 in the regulation of the renal epithelial sodium
      channel and more broadly implicate the circadian clock in control of sodium
      balance.

PMID- 19587448
TI  - The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno
      associated virus gene therapy vectors in mice.
AB  - Recombinant adeno-associated viruses (AAVs) have been used widely for in vivo
      gene therapy. However, adaptive immune responses to AAV have posed a significant
      hurdle in clinical application of AAV vectors. Recent advances have suggested a
      crucial role for innate immunity in shaping adaptive immune responses. How AAV
      activates innate immunity, and thereby promotes AAV-targeted adaptive immune
      responses, remains unknown. Here we show that AAV activates mouse plasmacytoid
      DCs (pDCs) via TLR9 to produce type I IFNs. In vivo, the TLR9-MyD88 pathway was
      crucial to the activation of CD8+ T cell responses to both the transgene product
      and the AAV capsid, leading to loss of transgene expression and the generation of
      transgene product-specific and AAV-neutralizing antibodies. We further
      demonstrate that TLR9-dependent activation of adaptive immunity targeting AAV was
      mediated by type I IFNs and that human pDCs could be activated in vitro to induce
      type I IFN production via TLR9. These results reveal an essential role for the
      TLR9-MyD88-type I IFN pathway in induction of adaptive immune responses to AAV
      and suggest that strategies that interfere with this pathway may improve the
      outcome of AAV-mediated gene therapy in humans.

PMID- 19587449
TI  - Hepatitis C virus versus innate and adaptive immune responses: a tale of
      coevolution and coexistence.
AB  - Since the identification of the hepatitis C virus (HCV) 20 years ago, much
      progress has been made in our understanding of its life cycle and interaction
      with the host immune system. Much has been learned from HCV itself, which, via
      decades of coevolution, gained an intricate knowledge of host innate and adaptive
      immune responses and developed sophisticated ways to preempt, subvert, and
      antagonize them. This review discusses the clinical, virological, and
      immunological features of acute and chronic hepatitis C and the role of the
      immune response in spontaneous and treatment-induced HCV clearance.

PMID- 19587450
TI  - "IF-pathies": a broad spectrum of intermediate filament-associated diseases.
AB  - Intermediate filaments (IFs) are encoded by the largest gene family among the
      three major cytoskeletal protein groups. Unique IF compliments are expressed in
      selective cell types, and this expression is reflected in their involvement, upon
      mutation, as a cause of or predisposition to more than 80 human tissue-specific
      diseases. This Review Series covers diseases and functional and structural
      aspects pertaining to IFs and highlights the molecular and functional
      consequences of IF-associated diseases (IF-pathies). Exciting challenges and
      opportunities face the IF field, including developing both a better understanding
      of the pathogenesis of IF-pathies and targeted therapeutic approaches.

PMID- 19587451
TI  - Introducing intermediate filaments: from discovery to disease.
AB  - It took more than 100 years before it was established that the proteins that form
      intermediate filaments (IFs) comprise a unified protein family, the members of
      which are ubiquitous in virtually all differentiated cells and present both in
      the cytoplasm and in the nucleus. However, during the past 2 decades, knowledge
      regarding the functions of these structures has been expanding rapidly. Many
      disease-related roles of IFs have been revealed. In some cases, the molecular
      mechanisms underlying these diseases reflect disturbances in the functions
      traditionally assigned to IFs, i.e., maintenance of structural and mechanical
      integrity of cells and tissues. However, many disease conditions seem to link to
      the nonmechanical functions of IFs, many of which have been defined only in the
      past few years.

PMID- 19587452
TI  - Intermediate filaments: primary determinants of cell architecture and plasticity.
AB  - Intermediate filaments (IFs) are major constituents of the cytoskeleton and
      nuclear boundary in animal cells. They are of prime importance for the functional
      organization of structural elements. Depending on the cell type, morphologically
      similar but biochemically distinct proteins form highly viscoelastic filament
      networks with multiple nanomechanical functions. Besides their primary role in
      cell plasticity and their established function as cellular stress absorbers,
      recently discovered gene defects have elucidated that structural alterations of
      IFs can affect their involvement both in signaling and in controlling gene
      regulatory networks. Here, we highlight the basic structural and functional
      properties of IFs and derive a concept of how mutations may affect cellular
      architecture and thereby tissue construction and physiology.

PMID- 19587453
TI  - Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility.
AB  - Epidermolysis bullosa (EB) simplex is a rare genetic condition typified by
      superficial bullous lesions that result from frictional trauma to the skin. Most
      cases are due to dominantly acting mutations in either keratin 14 (K14) or K5,
      the type I and II intermediate filament (IF) proteins tasked with forming a
      pancytoplasmic network of 10-nm filaments in basal keratinocytes of the epidermis
      and in other stratified epithelia. Defects in K5/K14 filament network
      architecture cause basal keratinocytes to become fragile and account for their
      trauma-induced rupture. Here we review how laboratory investigations centered on
      keratin biology have deepened our understanding of the etiology and
      pathophysiology of EB simplex and revealed novel avenues for its therapy.

PMID- 19587455
TI  - Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle
      disease.
AB  - Muscle fiber deterioration resulting in progressive skeletal muscle weakness,
      heart failure, and respiratory distress occurs in more than 20 inherited
      myopathies. As discussed in this Review, one of the newly identified myopathies
      is desminopathy, a disease caused by dysfunctional mutations in desmin, a type
      III intermediate filament protein, or alphaB-crystallin, a chaperone for desmin.
      The range of clinical manifestations in patients with desminopathy is wide and
      may overlap with those observed in individuals with other myopathies. Awareness
      of this disease needs to be heightened, diagnostic criteria reliably outlined,
      and molecular testing readily available; this would ensure prevention of sudden
      death from cardiac arrhythmias and other complications.

PMID- 19587454
TI  - Toward unraveling the complexity of simple epithelial keratins in human disease.
AB  - Simple epithelial keratins (SEKs) are found primarily in single-layered simple
      epithelia and include keratin 7 (K7), K8, K18-K20, and K23. Genetically
      engineered mice that lack SEKs or overexpress mutant SEKs have helped illuminate
      several keratin functions and served as important disease models. Insight into
      the contribution of SEKs to human disease has indicated that K8 and K18 are the
      major constituents of Mallory-Denk bodies, hepatic inclusions associated with
      several liver diseases, and are essential for inclusion formation. Furthermore,
      mutations in the genes encoding K8, K18, and K19 predispose individuals to a
      variety of liver diseases. Hence, as we discuss here, the SEK cytoskeleton is
      involved in the orchestration of several important cellular functions and
      contributes to the pathogenesis of human liver disease.

PMID- 19587456
TI  - Dysfunctions of neuronal and glial intermediate filaments in disease.
AB  - Intermediate filaments (IFs) are abundant structures found in most eukaryotic
      cells, including those in the nervous system. In the CNS, the primary components
      of neuronal IFs are alpha-internexin and the neurofilament triplet proteins. In
      the peripheral nervous system, a fifth neuronal IF protein known as peripherin is
      also present. IFs in astrocytes are primarily composed of glial fibrillary acidic
      protein (GFAP), although vimentin is also expressed in immature astrocytes and
      some mature astrocytes. In this Review, we focus on the IFs of glial cells
      (primarily GFAP) and neurons as well as their relationship to different
      neurodegenerative diseases.

PMID- 19587459
TI  - Role of surgery in brainstem gliomas.

PMID- 19587460
TI  - Neurosyphilis.

PMID- 19587457
TI  - Laminopathies and the long strange trip from basic cell biology to therapy.
AB  - The main function of the nuclear lamina, an intermediate filament meshwork lying
      primarily beneath the inner nuclear membrane, is to provide structural
      scaffolding for the cell nucleus. However, the lamina also serves other
      functions, such as having a role in chromatin organization, connecting the
      nucleus to the cytoplasm, gene transcription, and mitosis. In somatic cells, the
      main protein constituents of the nuclear lamina are lamins A, C, B1, and B2.
      Interest in the nuclear lamins increased dramatically in recent years with the
      realization that mutations in LMNA, the gene encoding lamins A and C, cause a
      panoply of human diseases ("laminopathies"), including muscular dystrophy,
      cardiomyopathy, partial lipodystrophy, and progeroid syndromes. Here, we review
      the laminopathies and the long strange trip from basic cell biology to
      therapeutic approaches for these diseases.

PMID- 19587461
TI  - Basilar invagination, Chiari malformation, syringomyelia: a review.
AB  - Institute and personal experience (over 25 years) of basilar invagination was
      reviewed. The database of the department included 3300 patients with
      craniovertebral junction pathology from the year 1951 till date. Patients with
      basilar invagination were categorized into two groups based on the presence
      (Group A) or absence (Group B) of clinical and radiological evidence of
      instability of the craniovertebral junction. Standard radiological parameters
      described by Chamberlain were used to assess the instability of the
      craniovertebral junction. The pathogenesis and clinical features in patients with
      Group A basilar invagination appeared to be related to mechanical instability,
      whereas it appeared to be secondary to embryonic dysgenesis in patients with
      Group B basilar invagination. Treatment by facetal distraction and direct lateral
      mass fixation can result in restoration of craniovertebral and cervical alignment
      in patients with Group A basilar invagination. Such a treatment can circumvent
      the need for transoral or posterior fossa decompression surgery. Foramen magnum
      bone decompression appears to be a rational surgical treatment for patients
      having Group B basilar invagination. The division of patients with basilar
      invagination on the basis of presence or absence of instability provides insight
      into the pathogenesis of the anomaly and a basis for rational surgical treatment.

PMID- 19587458
TI  - Functions of the intermediate filament cytoskeleton in the eye lens.
AB  - Intermediate filaments (IFs) are a key component of the cytoskeleton in virtually
      all vertebrate cells, including those of the lens of the eye. IFs help integrate
      individual cells into their respective tissues. This Review focuses on the lens
      specific IF proteins beaded filament structural proteins 1 and 2 (BFSP1 and
      BFSP2) and their role in lens physiology and disease. Evidence generated in
      studies in both mice and humans suggests a critical role for these proteins and
      their filamentous polymers in establishing the optical properties of the eye lens
      and in maintaining its transparency. For instance, mutations in both BFSP1 and
      BFSP2 cause cataract in humans. We also explore the potential role of BFSP1 and
      BFSP2 in aging processes in the lens.

PMID- 19587463
TI  - Transient ischemic attacks--definition, risk prediction and urgent management.
AB  - Recent evidence suggests that the risk of stroke in first few months after
      transient ischemic attack is higher than that was previously realized. There are
      clinical and imaging predictors which help in risk stratifying the patients to
      identify the high risk group who need immediate hospitalization and urgent
      evaluation. Recent advances in neuroimaging have revolutionized the evaluation of
      these patients. Further research is required in the deciding on the optimal
      treatment of these patients in the acute phase.

PMID- 19587462
TI  - A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal
      of the Indian TNM subcommittee on brain tumors.
AB  - BACKGROUND: There is no universally accepted staging system for primary brain
      tumors wherein prognostication is mainly based on complex composite indices. AIM:
      To develop a simple, pragmatic, and widely applicable grouping/staging system for
      gliomas, the most common primary brain tumor. MATERIALS AND METHODS: An expert
      neurooncology panel with representation from radiation oncology, neurosurgery,
      pathology, radiology, and medical oncology had several rounds of discussion on
      issues pertinent to brain tumor staging. The trade off was between the accuracy
      of prognostic categorization and a pragmatic, widely applicable approach. RESULTS
      AND RECOMMENDATIONS: The Tumor-Node-Metastasis staging was considered irrelevant
      for gliomas that seldom metastasize to lymphatics or outside the neuraxis.
      Instead, a 4-point staging/grouping system is proposed, using histological grade
      as the main prognostic variable and at least one stage migration based on other
      unfavorable features such as tumor location (brainstem); age (<5 years for all
      grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor
      neurological performance status (NPS 2-4); multicentricity and/or gliomatosis;
      and adverse biological parameters (proliferative index, angiogenesis markers,
      apoptotic index, cytogenetic abnormalities, and molecular markers). CONCLUSION:
      In absence of a grouping/staging system for primary brain tumors,
      prognostification is mostly based on complex composite indices. The proposed
      clinicopathobiological grouping/staging system for gliomas is a simple,
      pragmatic, and user-friendly tool with a potential to fulfill the objectives of
      staging classification.

PMID- 19587464
TI  - Current treatment strategy in the management of vestibular schwannoma.
AB  - BACKGROUND: The changing trends in the management of vestibular schwannoma (VS)
      in our practice over the last two decades as well as the current status are
      presented here. MATERIALS AND METHODS: The observations are based on the
      experience of 559 consecutive cases of VS operated by the first author between
      1987 and 2008, 438 of which were operated by microsurgery and 139 by gamma knife
      radiosurgery (GKR) (18 of which were previously operated by the authors). A
      detailed analysis of microsurgically managed patients in two different periods
      (100 consecutive patients each before 1993 and 2008) were compared to see the
      changing trend and document current results. RESULTS AND DISCUSSION: In the
      initial experience (1990s), the emphasis in microsurgery was preserving life,
      total excision of tumor and preservation of function in that order. In the 21 st
      century, the emphasis in microsurgery has been all about functional preservation.
      In 100 consecutive cases of VS (excluding neurofibromatosis-2) that were treated
      microsurgically between 2005-08, there were four small tumors (<2 cm), 14 medium
      sized tumors (2-3 cm) and 82 large tumors (>or=3 cm). The total excision rate was
      83%. The facial nerve anatomical preservation rate was 96% and function was Grade
      III House-Brackmann (HB) or better in 87%. Both the total excision rate and
      facial function of Grade II HB or better were 100% in cases with tumor size less
      than three cm. Functional hearing preservation was achieved in ten cases. There
      was no operative mortality. CONCLUSION: Total excision of VS, though aimed at, is
      no more pursued at the cost of facial function. Moreover, microsurgery,
      radiosurgery and observation are all valid options in the management of VS and
      choosing the correct modality helps in achieving optimal outcome.

PMID- 19587465
TI  - Differential PARP cleavage: an indication for existence of multiple forms of cell
      death in human gliomas.
AB  - BACKGROUND: Gliomas represent a diverse range of clinical presentation,
      histological differentiation, and response to therapy. Altered cell proliferation
      and cell death signals in gliomas are of great interest to elucidate the key
      molecules involved and to find effective treatment modalities. By considering the
      role of different proteases in correlation with differential poly (ADP-ribose)
      polymerase (PARP) fragmentation we have studied the pattern of cell death in
      human glioma tissues. MATERIALS AND METHODS: In our study, five different human
      glioma biopsies were collected and analyzed for the PARP cleavage pattern by
      using western immunoblotting. Samples were also analyzed for pro-caspase 3,
      calpain I (micro) and II (m), granzyme-B and apoptosis-inducing factor (AIF).
      Parallel sections of histologically confirmed astrocytoma and glioblastoma
      multiforme (GBM) were used for immunohistochemical analysis of cleaved caspase-3,
      granzyme B, AIF and cyclo-oxygenase -2 (cox-2). RESULTS: We found PARP
      fragmentation, along with usual approximately 89 kDa and approximately 24 kDa
      fragments, into other fragments of different molecular weights. Caspase mediated
      cell death may lead to appearance of larger approximately 89 kDa fragment and
      smaller approximately 24 kDa fragment indicating existence of apoptosis in the
      tumors. However, other fragments corresponding to approximately 64 kDa,
      approximately 54 kDa, and approximately 40 kDa were observed concomitantly in all
      glial tumor tissues. CONCLUSIONS: These results may indicate, not only apoptosis
      and necrosis, but there occurs the co-existence of intermediate cell death
      pathways in human glial tumors.

PMID- 19587466
TI  - Experience of microsurgical treatment of brainstem cavernomas: report of 37
      cases.
AB  - BACKGROUND: Cavernomas are rare in the brainstem and account for 18-35% of
      central nervous cavernomas and can cause recurrent hemorrhages, devastating
      neurological deficits and mortality. OBJECTIVES: To summarize the experience of
      microsurgical treatment of brainstem cavernomas and to investigate curative
      effect of microsurgical treatment of brainstem cavernomas. MATERIALS AND METHODS:
      A retrospective analysis clinical data of 37 patients with brainstem cavernomas
      seen between 2003 and 2007. The analysis included age distribution, hemorrhage
      rates, clinical presentation, location of the lesions, and preoperative and
      postoperative Karnofsky Performance Scale (KPS) scores. The surgical indications,
      the timing of surgery and the surgical techniques were also assessed. RESULTS:
      All the 37 patients received microsurgical resections, there was no surgery
      related mortality. Histopathological examination confirmed the diagnosis of
      cavernoma. Postoperatively, 20 patients had functional improvement, 15 patients
      had no change in the neurological status, and two patients deteriorated. Early
      surgery was associated with better outcomes. Mean followed up period was 21.5
      months (range 6-36 months). During the follow-up 20 patients had resumed
      activities of daily living (KPS scores of 90-100), 10 patients were able to self
      care with some efforts (KPS scores of 70-80), five patients needed considerable
      assistance (KPS score of 50-60) and two patients suffered hemiparesis (KPS scores
      of 40). None of the patient had recurrent hemorrhage. CONCLUSIONS: Brainstem
      cavernomas can safely be resected. Successful resection of brainstem cavernomas
      can be achieved by optimal surgical approaches, feasible entry zone and
      meticulous microsurgical techniques. The goal of surgical intervention should be
      the total resection of the lesion without any deteriorative in the neurological
      deficits.

PMID- 19587467
TI  - Surgical considerations for 'intrinsic' brainstem gliomas: proposal of a
      modification in classification.
AB  - BACKGROUND: Brainstem gliomas are highly heterogeneous tumors both in their
      clinical manifestation and in their pathology. Despite significant advances in
      the surgery for brainstem gliomas many aspects of this pathology are still
      unclear. OBJECTIVE: To evaluate the clinical, radiological and surgical outcome
      of 40 focal 'intrinsic' brainstem gliomas and propose a surgical strategy
      oriented classification. MATERIALS AND METHODS: A total of 40 focal 'intrinsic'
      ("expanding variety") tumors have been operated over a period of 8.5-years
      (January 1998-June 2007). Our criteria included patients with (1) well-defined
      gadolinium enhancing tumor; (2) relatively long duration of symptoms (> six
      months) and (3) good neurological functional status and independent for all
      activities of daily living. The cutoff size of 2 cm was not rigidly adhered to.
      RESULTS: The 'intrinsic' brainstem tumors were classified into three types:
      Expanding, diffuse infiltrative and pure ventral varieties. Only patients with
      expanding variety of brainstem gliomas were subjected to surgery, mean age 19.2
      years (range 4-55 years) and male to female ration mean: 3:2). The tumor location
      included pons (n=19), midbrain (n=13) and medulla (n=8). Surgical approaches
      included midline suboccipital (n=28), retromastoid (n=7), subtemporal (n=3) and
      supracerebellar-infratentorial (n=2). Thirty-two cases with 'diffuse
      infiltrative' and 'pure ventral' variety were given radiotherapy only. Histology
      pathology revealed pilocytic variety (n=10), Grade II (n=17) and Grade III
      (n=13). There was one death in the surgical series (due to aspiration).
      Complications included meningitis (n=2), wound infection (n=1), chest infection
      (n=5) and transient mutism (n=1). Follow-up ranged from 3-68 months. Overall, 36
      improved /remained same and three worsened in their clinical status at the time
      of discharge. CONCLUSION: The surgical management of intrinsic brainstem tumors
      presents a surgical challenge; radical excision yielded a good outcome in the
      majority of cases. The authors propose a classification system for 'intrinsic'
      brainstem tumors for defining surgical strategy.

PMID- 19587468
TI  - "Finger drop sign" in Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barriota syndrome (GBS) is an acute neurological illness
      affecting the peripheral nervous system causing significant morbidity. The
      syndrome has been classified electrophysiologically into demyelinating and axonal
      forms. The clinical features of the axonal variant (acute motor axonal neuropathy
      -AMAN) are not well characterized, particularly in the Indian context. OBJECTIVE:
      To assess the incidence, clinical presentation and disease course of patients
      with AMAN. MATERIALS AND METHODS: This is an observational study done at a
      tertiary referral center in South India. The study period extended from January
      2006 to July 2007. All patients with a clinical diagnosis of GBS and satisfying
      the electrophysiological criteria for AMAN were included. RESULTS: There were 12
      cases of AMAN out of a total of 84 cases of GBS. All AMAN patients showed a
      characteristic pattern of hand weakness predominant weakness of finger extensors
      with relatively normal power in finger flexors, wrist flexors and extensors.
      Proximal limb weakness was mild and was present in 85% cases. One patient had
      cranial nerve palsy and one had hyperreflexia. None of the patients progressed to
      respiratory failure. CONCLUSION: AMAN is a distinct subgroup in GBS showing
      certain distinguishing features, the most notable being predominant weakness of
      finger extensors.

PMID- 19587469
TI  - An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course
      of Guillain Barre syndrome.
AB  - BACKGROUND: Elevated cerebrospinal fluid (CSF) total protein (TP) concentration
      (mainly due to a dysfunctional blood-CSF barrier (B-CSFB)) with normal cell count
      is a hallmark for the diagnosis of Guillain-Barriota syndrome (GBS). AIMS: This
      work presents the evaluation of B-CSFB dysfunction with respect to the course,
      severity, and clinical features of GBS. MATERIALS AND METHODS: A sample of CSF
      was collected on admission from 68 patients of both genders (15 children and 53
      adults) diagnosed with GBS. A follow-up CSF sample was obtained approximately 15
      days after admission. TP concentration was determined in the CSF and 7.5%
      polycrylamide gel electrophoresis was employed for serum and CSF protein
      fractioning. A low percentage of prealbumin fraction was considered a test of
      impaired B-CSFB. RESULTS: Elevated TP concentration and lower prealbumin were
      observed in almost 70% of the patients on admission, but this percentage was
      lower (52.4%) during the first week from onset of symptoms. Both variables were
      directly associated with the time of evolution of the disease and also with a
      greater clinical severity. Follow-up CSF studies showed higher CSF TP and lower
      prealbumin percentages, while deceased patients did not display this response
      pattern in the follow-up CSF. CONCLUSIONS: B-CSFB dysfunction was present in only
      half of the patients with GBS during the first week from onset and it was
      directly associated with progression and clinical severity; nevertheless, a low B
      CSFB dysfunction response during follow-up was associated with a lethal outcome,
      suggesting it could also serve a 'protective' effect during regeneration.

PMID- 19587470
TI  - Once daily baclofen sustained release or gastro-retentive system are acceptable
      alternatives to thrice daily baclofen immediate release at same daily dosage in
      patients.
AB  - BACKGROUND: Baclofen, a GABA-agonist, is currently available as an immediate
      release (IR) formulation for relieving neurogenic spasticity in a variety of
      disorders. Baclofen IR requires to be administered three times a day which
      inadvertently increases the chances of medication noncompliance among patients
      and is also associated with side effects such as drowsiness and muscle weakness.
      AIM: To overcome the shortcomings of baclofen IR, two modified formulations,
      baclofen sustained release (SR) and gastric retentive system (GRS), have been
      proposed to be equivalent in efficacy to baclofen IR with the administration of a
      single daily dose. MATERIALS AND METHODS: Ninety patients with chronic neurogenic
      muscular spasticity were enrolled requiring 10-20 mg of baclofen IR every eight
      hours. The patients were randomized to two treatment arms: SR (n = 46) or GRS (n
      = 44) at the same once-daily dose for four weeks. Efficacy was measured by
      Ashworth score for muscle tone, spasm score, reflex score, 30-item functional
      independence score, and patient's diary score for three most affected activities
      of daily life. RESULTS: The mean Ashworth score changed significantly (P = 0.00)
      for patients in the SR group from 3.03-2.69 (-0.35) and 3.07-2.70 (-0.37) for
      patients in the GRS group. There was no significant difference (P = 0.87) between
      baseline-adjusted Ashworth score reductions on SR (-0.35) and GRS (-0.37).
      Similar results were obtained for spasm, reflex, and functional independence
      scores. The mean baseline-adjusted patient-diary scores did not differ
      significantly between 8 am, 12 pm, 4 pm, and 8 pm (P = 0.96), either on SR (-5.3
      to -6.1) or GRS (-7.3 to -8.1), indicating a uniform effect round-the-day on
      both. Further, sedation scores (mean +/- SEM) decreased significantly (P < 0.05)
      on both SR (10.36 +/- 1.37 to 6.18 +/- 0.92) and GRS (8.14 +/- 1.57 to 5.33 +/-
      1.11), suggesting better toleration. CONCLUSION: Once-daily baclofen SR and GRS
      are efficacious, convenient, and better-tolerated alternatives to baclofen IR in
      patients with neurogenic spasticity.

PMID- 19587471
TI  - The efficacy and safety of gabapentin in carpal tunnel patients: open label
      trial.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy
      caused by median nerve compression at the wrist. It results in loss of
      considerable man days and the effectiveness the various treatment modalities are
      still debated. AIM: To study the efficacy of gabapentin in patients with CTS. The
      study aim is to investigate the efficacy of gabapentin in patients with CTS
      patients who were refractory to the other conservative measures or unwilling for
      the surgical procedure. MATERIALS AND METHODS: Forty one patients diagnosed as
      idiopathic CTS were included in the study. Patients were assessed with symptom
      severity scale (SSS) and functional status scale (FSS) scores of Boston Carpal
      Tunnel Questionnaire (BCTQ) before and at 1, 3, and 6 months of the treatment.
      Response to therapy was determined by using SSS and FSS scores of BCTQ. RESULTS:
      The median dosage of gabapentin was 1800 mg/daily. Side effects were mild and
      transient. There was a statistically significant difference in both symptom SSS
      and FSS scores between before and after treatment in patient groups at the end of
      six months (P < 0.001). According to grading the changes in subscales of BCTQ, of
      41 patients, 34.1 and 29.3 had a >or= 40% decrease in SSS and FSS, respectively.
      CONCLUSION: Gabapentin was found to be partially effective and safe in
      symptomatic treatment of CTS patients.

PMID- 19587473
TI  - Mechanical device the Penumbra system in the management of acute stroke: report
      of five cases.
AB  - Use of mechanical devices in acute ischemic stroke has shown promise not only in
      recanalization rates but also with better clinical outcome and also extension of
      the window period to 8 hours. This is the first reported series of use of
      mechanical devices in India. We report five patients with acute stroke in whom
      mechanical devices (Penumbra System, Alameda, California) were used for
      thrombolysis. All the treated vessels (100%) were successfully re-canalized,
      Trials In Myocardial Infarction (TIMI) score of 3. At 90-day follow-up, of the 5
      patients treated, 2 had modified Rankin score (mRS) of < 2. This small series
      shows the safety and efficacy of the Penumbra System in the thrombolysis of large
      vessel occlusive disease.

PMID- 19587472
TI  - Comparison of the analgesic effect of ibuprofen with mesalamine after discectomy
      surgery in patients with lumbar disc herniation: a double-blind randomized
      controlled trial.
AB  - BACKGROUND: Pain management is an important component in the postoperative period
      following discectomy. AIMS: We hypothesized that mesalamine considering its
      better safety profile, is likely to be a better choice, if it would be as
      effective as ibuprofen in controlling post-discectomy pain. SETTINGS AND DESIGN:
      A double-blind randomized controlled trial was performed on patients who
      underwent lumbar discectomy surgery. MATERIALS AND METHODS: Of the 58 patients
      who had lumbar discectomy, 27 patients were randomized to oral ibuprofen 500 mg
      and 31 patients to mesalamine 400 mg, three times a day for nine days following
      surgery. There was no placebo group. Severity of pain was assessed by using 10-
      cm visual analogue scale (VAS), once before operation and for nine days after.
      STATISTICAL ANALYSIS: Mean +/- SD pain scores were compared between groups and
      the statistical difference was estimated by Student's test using SPSS (Version
      13). We also calculated the power of each t-test. Repeated measure ANOVA was
      performed for measuring the effect of time. RESULTS: The age range of the
      patients was 35 to 60 years (mean: 42.2 years). Mean +/- SD preoperative pain
      scores for ibuprofen or mesalamine-treated groups were 7.852 +/- 2.441 and 7.806
      +/- 2.892, respectively. At the end of day 9, mean +/- SD of pain score was 2.704
      +/- 2.284 and 2.717 +/- 2.273 for ibuprofen and mesalamine-treated groups
      respectively. Both drugs significantly reduced postoperative pain and there was
      no statistically significant difference between the two groups. CONCLUSIONS:
      Since both drugs showed almost equal analgesic effect, considering its safety
      profile mesalamine, seems to be the preferred choice to alleviate post-discectomy
      surgery pain.

PMID- 19587474
TI  - Intra-arterial thrombolysis in basilar artery occlusions combination of intra
      arterial thrombolytics and Gp IIb/IIIa inhibitors in basilar artery thrombosis.
AB  - Basilar artery thrombosis has high morbidity and mortality. Though intra-arterial
      thrombolytics have proven efficacy in the treatment of acute basilar artery
      occlusion, the elevation of procoagulant factors in the blood after intra
      arterial thrombolysis could result in subsequent thrombus formation and clinical
      deterioration. Glycoprotein IIb/IIIa inhibitors have been shown to reduce this
      elevation in procoagulants. We present a pilot study of three cases of acute
      basilar artery occlusion treated with a combination of intra-arterial
      thrombolytics and Gp IIb/IIIa inhibitor with remarkable clinical recovery seen in
      all the patients.

PMID- 19587475
TI  - Retained surgical sponge in differential diagnosis of paraspinal soft-tissue mass
      after posterior spinal surgery: report of eight cases.
AB  - BACKGROUND: In the postoperative period of posterior spinal surgery, surgeons
      usually encounter a wide spectrum of complications, including retained surgical
      sponge, gossypiboma. MATERIALS AND METHODS: Retrospective review of case records
      of eight patients diagnosed with gossypiboma with emphasis on computed tomography
      (CT) and magnetic resonance imaging (MRI) findings. RESULTS: All the eight
      patients presented with low back pain and/or symptoms of infection, such as
      draining from the incision site, fever, and tenderness. The diagnosis was
      confirmed by the imaging findings on MRI with gadolinium enhancement. CONCLUSION:
      Retained paravertebral surgical sponges are seldom reported due to medicolegal
      implications. Awareness of this complication among neurosurgeons and radiologists
      is essential to avoid unnecessary morbidity.

PMID- 19587476
TI  - Spontaneous intracranial extradural hematoma: case report and literature review.
AB  - Spontaneous extradural hematoma (EDH) is an uncommon form of intracranial
      hematoma and is caused by the adjacent sinus and otic infections, dural vascular
      malformations and disorders of blood coagulation. We report spontaneous EDH in a
      54-year old women with chronic kidney disease (CKD) on intermittent hemodialysis.
      She was successfully managed by conservative treatment. The EDH in her was
      probably related to the coagulation abnormalities associated with CKD,
      hemodialysis or heparin use during the dialysis.

PMID- 19587477
TI  - Surgical extraction of migrated coils via proximal segment of the anterior
      cerebral artery: an emergency alternative.
AB  - Coil migration is a severe complication in endovascular treatment. We report our
      experience of prompt surgical extraction of migrated coils via excised proximal
      A1 following endovascular embolization of intracranial aneurysms in two patients.
      Both patients had to undergo coiling or stent-assisted coiling for cerebral
      aneurysms, and while operating the coils protruded and migrated to the
      bifurcation of internal carotid artery and middle cerebral artery. Immediate
      craniotomy was performed after unsuccessful or unfeasible endovascular retrieval.
      The migrated coils were removed via excised proximal A1, and the patients
      recovered well without any neurological deficits. We suggest that this surgical
      procedure might be an alternative route in selected patients with good cross
      circulation in emergency. In addition, a rare occasion of coil migration after
      stent-assisted coiling is also described in one patient, which might have
      resulted from unsatisfactory wall apposition of the stent due to a curved vessel.

PMID- 19587478
TI  - Transorbital penetrating cerebral injury with a ceramic stone: report of an
      interesting case.
AB  - Penetrating cranial injury is a potentially life-threatening condition. The
      majority of war injuries are high-velocity penetrating cranial injuries; but in
      civilian cases, most penetrating cranial wounds are low-velocity type. We report
      an interesting case of transorbital penetrating cranial injury with a knife
      sharpening stone made up of ceramic in a 28-year-old male. The pertinent
      literature is reviewed and management of such cases is discussed.

PMID- 19587479
TI  - Peroral extrusion of ventriculoperitoneal shunt: case report and review of
      literature.
AB  - A rare complication of ventriculoperitoneal shunting (VPS) is bowel perforation
      by the peritoneal catheter of the shunt tube. Rarer still is the peroral
      extrusion of such a perforated shunt. A two-month-old infant with history of
      neonatal meningitis, presented with a large head, bulging fontanelle, and
      hydrocephalus. A VPS was inserted. The child was doing well till the age of eight
      months, when following vomiting, the peritoneal end of the shunt came out through
      the mouth. The shunt was removed and antibiotics started. At follow up after 12
      months, the child was doing well. Peroral extrusion of the shunt tube needs
      prompt treatment, including removal of the extruded shunt tube, and attention to
      bowel perforation and possible cerebrospinal fluid infection. The reported
      patient is younger than the five cases reported earlier. Strategies in the
      management of this complication are reviewed. An individualized approach is
      essential for the successful treatment of this rare complication.

PMID- 19587480
TI  - An anatomical variation of the third common digital nerve and recurrent motor
      branch of the median nerve.
AB  - Carpal tunnel syndrome (CTS) is an entrapment neuropathy where the median nerve
      is compressed in the carpal canal. There are many variations of the distal
      branches of the median nerve at the wrist. Anatomical variations of this nerve
      have fundamental clinical importance to prevent injuries, especially during
      limited open or endoscopic surgical procedures. A case is presented of an
      anomalous course of the recurrent motor branch of the median nerve and high
      division of the third common digital nerve seen in a limited open carpal tunnel
      release.

PMID- 19587481
TI  - Intrathyroidal parathyroid adenoma presenting with neuromuscular manifestation.
AB  - Primary hyperparathyroidism (PHPT) is not an uncommon endocrine disorder. We
      describe a patient with PHPT who presented with progressive proximal limbs
      weakness and dystrophic changes of leg muscles. Serum calcium, alkaline
      phosphatase, and parathyroid hormone were elevated and serum phosphorus was low.
      Neck computerized tomography scan showed a parenchymatous tumor in the right lobe
      of the thyroid. The tumor presented as a 'cold nodule' in the dual-phase single
      agent Tc-99m MIBI scan. The right lobectomy examination confirmed the diagnosis
      of an intrathyroidal parathyroid adenoma of the right gland.

PMID- 19587482
TI  - Left subclavian artery aneurysm secondary to syphilitic arteritis presenting with
      a right ischemic cerebellar infarction.
AB  - We report a 28-year-old male who presented with severe vertigo, vomiting,
      diplopia, clumsiness of right extremities. Physical examination revealed low
      reading of blood pressure in the left upper limb and evidence of mild left upper
      limb ischemia. On neurological examination he had right cerebellar ataxia.
      Computed tomography and magnetic resonance imaging, revealed an acute right
      cerebellar infarction in the anterior inferior cerebellar artery territory.
      Doppler ultrasono-graphy revealed an aneurysm of the left subclavian artery. The
      patient was tested positive for serology of syphilis.

PMID- 19587483
TI  - Chorea as the presenting feature of neurosyphilis.
AB  - Syphilis is still a significant public health problem in developing countries.
      Although chorea is a very rare manifestation of neurosyphilis, it might be on
      occasions the initial symptom. This report presents a patients with neurosyphilis
      who had chorea as the initial presenting symptom.

PMID- 19587484
TI  - Multiple giant cavernous angiomas of the brain.

PMID- 19587485
TI  - Post-traumatic isolated superior rectus hematoma.

PMID- 19587486
TI  - Azithromycin-induced myasthenic crisis: reversibility with calcium gluconate.

PMID- 19587488
TI  - 'Garland sign' in amyotrophic lateral sclerosis.

PMID- 19587487
TI  - Conus ependymoma with holocord syringomyelia.

PMID- 19587489
TI  - Comprehensive rural epilepsy surveillance programme in Uttarakhand state of
      India.

PMID- 19587490
TI  - Rapid resolution of hydrocephalus due to simultaneous movements of hematoma in
      the trigono-occipital horn and the aqueduct.

PMID- 19587491
TI  - Intracranial epidermoid cyst: magnetic resonance imaging features.

PMID- 19587492
TI  - Fibrolipomatous hamartoma of the median nerve presenting with carpal tunnel
      syndrome.

PMID- 19587493
TI  - Renal replacement therapy in sepsis-induced acute renal failure.
AB  - Acute renal failure (ARF) is a common complication of sepsis and carries a high
      mortality. Renal replacement therapy (RRT) during the acute stage is the mainstay
      of therapy. Va-rious modalities of RRT are available. Continuous RRT using
      convective methods are preferred in sepsis-induced ARF, especially in
      hemodynamically unstable patients, although clear evidence of benefit over
      intermittent hemodialysis is still not available. Peritoneal dialysis is clearly
      inferior, and is not recommended. Early initiation of RRT is probably
      advantageous, although the optimal timing of dialysis is yet unknown. Higher
      doses of RRT are more likely to be beneficial. Use of bio-compatible membranes
      and bicarbonate buffer in the dialysate are preferred. Anticoagulation during
      dialysis must be carefully adjusted and monitored.

PMID- 19587494
TI  - Sodium balance-an integrated physiological model and novel approach.
AB  - Various physiological mechanisms regulate sodium and water balance in the human
      body. These processes achieve acute and chronic sodium regulation and the
      simultaneous or sequential changes can be explained using a single physiological
      model. Steady intracellular water and osmolality is necessary for cell membrane
      integrity and cellular processes. Body fluids protect circulatory blood volume by
      altering Na + and water balance. This is the most vital homeostatic function of
      the body. Changes in ECF volume are sensed by various cardinal sensors.
      Physiologically, the main aim of Na + and water balance is to permit variable
      salt and water intake without large fluctuations in blood pressure or volume
      status. Homeostatic processes act in an integrated fashion to protect against any
      perturbations. Characteristically, these mechanisms are sequential as well as
      parallel. These may be synergistic or antagonistic to each other. Rapidity,
      sensitivity and potency of these powerful feedback systems differ. Various
      physiological and pathological insults determine the magnitude of response of
      these systems.

PMID- 19587495
TI  - Vascular complications following 1500 consecutive living and cadaveric donor
      renal transplantations: a single center study.
AB  - The aim of this study was to document vascular complications that occurred
      following cadaveric and living donor kidney transplants in order to assess the
      overall incidence of these complications at our center as well as to identify
      possible risk factors. In a retrospective cohort study, 1500 consecutive renal
      transplant recipients who received a living or cadaveric donor kidney between
      December 1988 and July 2006 were evaluated. The study was performed at the
      Nemazee Hospital, Shiraz, Iran. The assessment of the anatomy and number of renal
      arteries as well as the incidence of vascular complications was made by color
      doppler ultrasonography, angiography, and/or surgical exploration. Clinically
      apparent vascular complications were seen in 8.86% of all study patients (n =
      133) with the most frequent being hemorrhage (n = 91; 6.1%) followed by allo
      graft renal artery stenosis (n = 26; 1.7%), renal artery thrombosis (n = 9;
      0.6%), and renal vein thrombosis (n = 7; 0.5%). Vascular complications were more
      frequent in recipients of cadaveric organs than recipients of allografts from
      living donors (12.5% vs. 7.97%; P= 0.017). The occurrence of vascular
      complications was significantly more frequent among recipients of renal
      allografts with multiple arteries when compared with recipients of kidneys with
      single artery (12.3% vs. 8.2%; P= 0.033). The same was true to venous
      complications as well (25.4% vs. 8.2%; P< 0.001). Our study shows that vascular
      complications were more frequent in allografts with multiple renal blood vessels.
      Also, the complications were much less frequent in recipients of living donor
      transplants.

PMID- 19587496
TI  - Risk factors of post renal transplant hyperparathyroidism.
AB  - It is well recognized that patients with end stage renal diseases (ESRD) have
      hyper-plastic parathyroid glands. In most patients, a decrease in parathyroid
      hormone (PTH) occurs by about 1 year after renal transplantation. However, some
      renal transplant recipients continue to have elevated level of PTH. We
      prospectively evaluated 121 patients undergoing renal transplantation between
      August 2000 and 2002. The duration of dialysis, calcium (Ca), phosphorus (P),
      albumin, creatinine and iPTH levels were recorded prior to transplantation and
      three months and one year after transplantation. These 121 patients were on
      dialysis for an average period of 17.4 months prior to transplantation. An
      increase in the serum Ca and a decrease in serum P and iPTH level was seen in the
      patients after transplantation (P< 0.001). Hyperparathyroidism was in 12 (9.9%)
      and 7 (5.7%) patients three months and one year after transplantation
      respectively. Elderly patients and patients with longer duration on dialysis had
      an increased risk of developing post transplant hyperpara-thyroidism and
      hypercalcemia in the first year post transplant (P< 0.05). In conclusion age and
      duration on dialysis before transplantation seems to be important risk factors
      for post transplant hyperparathyroidism.

PMID- 19587498
TI  - The efficacy of darbepoetin alpha in hemodialysis patients resistant to human
      recombinant erythropoietin (rHuEpo).
AB  - Darbepoetin due to longer half life is convenient and effective for long term.
      This study was done to assess the efficacy of darbepoetin in the treatment of
      patients on high doses of erythropoietin (EPO) and to compare its efficacy in
      patients resistant and responsive to EPO. This is a prospective, controlled open
      label study assessing the efficacy of darbepoetin in 55 hemodialysis patients on
      high dose EPO and comparing its efficacy in the patients who were "EPO 
      resistant" (group 1, n= 28) and in those who were "EPO-responsive" (group 2, n=
      27). The initial conversion ratio was 380 mcg darbepoetin: 1 U EPO/ week and the
      dose of darbepoetin was adjusted thereafter at fortnightly intervals with the aim
      of achieving and maintaining the hemoglobin level between 11-12 g/dL. The
      patients were followed up for 12 weeks following the introduction of darbepoetin.
      The impact of gender, baseline PTH, age, Kt/V, duration on dialysis, initial EPO
      dose on the response to darbepoetin was investigated. Continuous variables were
      compared using two tailed t-test and non-parametric by Fisher exact test. Overall
      darbepoetin was effective with 85.5 % of the patients responding and 21.8 % of
      the patients' able to maintain their hemoglobin with once fortnightly dose by the
      end of the study. Mean darbepoetin dose and the mean EPO to darbepoetin
      conversion ratio on completion of the study were 58.2 (42.4) mcg/week (0.983
      (0.87) mcg/kg/week) and 384:1 respectively. Hemoglobin levels in groups 1
      improved from 9.8 +/- 0.9 g/dL to 12.0 +/- 1.4 g/dL (0.0001) and 2 were and
      maintained it in group 2 at 11.9 +/- 1.3 g/dL (P= 0.79). The doses of darbepoetin
      required in groups 1 and 2 were similar (54.3 +/- 33 and 53.9 +/- 47 mcg/week (P=
      0.97) respectively and 0.89 +/- 0.6 and 0.98 +/- 1.0 mcg/kg/week (P= 0.8). 22
      (78.6 %) of the EPO resistant patients responded to darbepoetin. In conclusion
      conversion from high dose EPO to darbepoetin proved successful even in patients
      who were resistant to EPO. The darbepoetin dose required in the EPO resistant and
      EPO responsive groups did not differ significantly and age, duration on dialysis
      and baseline PTH level had no impact on responsiveness to EPO or darbepoetin.

PMID- 19587497
TI  - Crossmatch testing in kidney transplantation: patterns of practice and
      associations with rejection and graft survival.
AB  - Methods of crossmatch testing prior to kidney transplantation are not
      standardized and there are limited large-scale data on the use and outcomes
      implications of crossmatch modality. Data describing the most sensitive
      crossmatch modality for crossmatch-negative kidney transplants were drawn from
      the Organ Procurement and Transplant Network Registry. Within the cohort
      transplanted in 1999-2005, we identified patient and transplant characteristics
      predictive of each testing modality by multivariate logistic regression. We
      assessed associations of crossmatch modality with rejection risk by logistic
      regression and with graft survival by Cox's hazards analysis. Among 230,995
      transplants, use of flow cytometry with T-and B-lymphocytes (T&B FC) increased
      progressively in 1987-2005. Among the recent transplants performed in 1999-2005
      (n=64,320), negative T&B FC crossmatch was associated with 15% lower relative
      risk of first-year acute rejection (adjusted HR 0.85, 95% CI 0.80-0.89) compared
      to negative T-antihuman-globulin and B-National Institutes of Health/Wash (T AHG
      &B) crossmatch. Five-year graft survival after transplant with negative T&B FC
      (82.6%) was modestly better than after negative T AHG &B (81.4%, P= 0.008) or T
      AHG crossmatch (81.1%, P 0.0001), but on adjusted analysis was significantly
      different only among recipients from deceased donors and patients aged > 60
      years. Many subgroups for whom negative T&B FC crossmatch predicted lower
      rejection risk (Caucasians, deceased donor recipients, re-transplants) were not
      more likely to be crossmatched by this method. We conclude that current practice
      patterns have not aligned utilization of T&B FC crossmatch with associated
      benefits. Prospective evaluation of the relationship of crossmatch modality with
      outcomes is warranted.

PMID- 19587499
TI  - Effect of dialysate temperature on hemodynamic stability among hemodialysis
      patients.
AB  - Cooling the dialysate below 36.5 degrees C is an important factor that
      contributes to hemodynamic stability in patients during hemodialysis (HD). In
      this study, the effect of dialysate temperature on hemodynamic stability,
      patients' perception of dialysis discomfort and post dialysis fatigue were
      assessed in a group of patients on HD. A total of 50 patients, all of whom were
      on 3-times-per-week dialysis regimen, were studied. Patients were assessed during
      six dialysis sessions; in three sessions, the dialysate temperature was normal
      (37 degrees C) and in three other sessions, the dialysate temperature was low (35
      degrees C). Specific scale questionnaires were used in each dialysis session, to
      evaluate the symptoms during the dialysis procedure as well as post-dialysis
      fatigue, and respective scores were noted. The results showed that usage of low
      dialysate temperature was associated with the following: higher post dialysis
      systolic blood pressure (P< 0.05) and lower post dialysis heart rate (P< 0.01),
      with similar ultrafiltration rates, better intra-dialysis symptoms score and post
      dialysis fatigue scores (P< 0.001, and P < 0.001, respectively), shorter post
      dialysis fatigue period (P< 0.001) as well as higher urea removal (P< 00001) and
      Kt/V (P< 0.0001). Patients' perceptions were measured by a questionnaire, which
      showed that 76% of them felt more energetic after dialysis with cool dialysate
      and requested to be always dialyzed with cool dialysate. Low temperature
      dialysate is particularly beneficial for highly symptomatic patients, improves
      tolerance to dialysis in hypotensive patients and helps increase ultrafiltration
      while maintaining hemodynamic stability during and after dialysis.

PMID- 19587500
TI  - Serum trypsin inhibitory capacity in hemodialysis patients.
AB  - It has been established that overproduction of reactive oxygen species (ROS)
      occurs during hemodialysis causing oxidation of proteins. Alpha-1-antitrypsin is
      the major circulating anti-protease which contains methionine in the active site.
      The aim of the present study was to measure the level of serum trypsin inhibitory
      capacity (sTIC) in hemodialysis patients. This case-control study was performed
      in 52 hemodialysis patients and 49 healthy controls. sTIC was measured by
      enzymatic assay. The sTIC was significantly (P< 0.001) lower in hemodialysis
      patients (1.87 +/- 0.67 micromol/min/mL) than healthy controls (2.83 +/- 0.44
      micromol/min/L). Reduction of sTIC may be due to the oxidation of methionine
      residue in the reactive site of alpha-1 antitrypsin.

PMID- 19587501
TI  - Childhood primary glomerular diseases in the western region of Saudi Arabia.
AB  - We report our institute experience on primary glomerular disease in children in
      the western region of Saudi Arabia over the last 18 years (1988 to 2006). A total
      of 169 cases were identified as primary glomerular diseases in children and
      adolescent with age range from first year of life till 18 years. Minimal change
      disease and focal segmental glomerulosclerosis were the commonly encountered
      primary glomerular diseases (20.1%and 19.5% respectively), mesangioproliferative
      glomerulonephritis IgM nephropathy (14.8%), IgA nephropathy (10.7%),
      postinfectious glomerulonephritis (9.5%), membranous glomerulonephritis (7.1%),
      membranoproliferative glomerulonephritis (5.9%) and mesangioproliferative
      glomerulonephritis with negative immunofluorescence (5.9%). The less frequently
      encountered primary glomerular diseases were congenital nephritic syndrome
      Finnish type (2.4%), Alport syndrome (2.4%), dense deposit disease (1.2%), and
      mesangio-proliferative glomerulonephritis with IgG positive (0.6%). We concluded
      that minimal change disease and focal segmental glomerulosclerosis are the most
      common primary glomerular disorder en-countered in children in our series and
      with similar age distribution.

PMID- 19587502
TI  - The prevalence of virulence genes of E. coli strains isolated from children with
      urinary tract infection.
AB  - To evaluate the prevalence of virulence genes in E. coli strains isolated from
      urine samples of children with urinary tract infection(UTI) and their correlation
      with clinical data, we isolated E. coli strains from urine samples of children
      with UTI during the period of August 2005 - August 2006 and studied them for the
      presence of the virulence genes by PCR. A total of 96 E. coli strains were
      isolated. The prevalence of genes, pyelonephritis associated pili (pap genes), S
      family adhesions (sfa gene), hemolysin (hly gene), and cytotoxic nercotizing
      factor type 1 (cnf-1-1 gene) among the isolated strains was 27.1%, 14.6%, 13.5%
      and 22.9 %, respectively. Pyelonephritis was more prevalent in the cases with
      positive virulence genes. The results showed significant correlation between age
      of the patient and the presence of the genes (P< 0.05). Cnf-1 gene was
      significantly more common in samples of patients with abnormal finding on the
      ultrasound of kidneys (P= 0.049). Our study demonstrated higher prevalence of
      pyelonephritis in the presence of E. coli virulence genes. Detection of the genes
      in urine samples may help in the management of UTI.

PMID- 19587503
TI  - Renal involvement in Behcet's disease.
AB  - There are conflicting reports about the renal involvement in Behcet's disease
      (BD). In this study we aimed to study the frequency and type of renal involvement
      in a group of patients with BD in Azerbaijan province that is one of the
      prevalent areas of BD in Iran. All cases of BD were prospectively followed
      between June 2004 and January 2007, and evaluated for renal dys-function (serum
      creatinine > 1.7 mg/dL), glomerular hematuria and proteinuria. Those patients
      with proteinuria > 500 mg/day and serum creatinine level > 2 mg/dL, underwent
      renal biopsy. From a total number of 100 patients, six patients (6%) had obvious
      renal involvements. Four patients had glomerular hematuria and proteinuria. Renal
      biopsy in two of them revealed measangial proliferative glumerulonephritis with
      IgA deposit in one of them and membranoproliferative glumerolonephritis in
      another one. Two remaining patients had serum creatinine > 2 mg/dL without any
      hematuria or proteinuria. Serologic study for viral agents and collagen vascular
      disease were negative in all patients with renal involvements. In conclusion,
      renal involvement in BD is not infrequent, although in most cases it is mild in
      nature and may be missed.

PMID- 19587504
TI  - Risk factors of hyperparathyroidism in advanced stages of chronic kidney disease.
AB  - The pathogenesis of renal osteodystrophy is not clearly defined. We evaluate in
      this study the potential effect of demographic and biochemical markers on
      parathormone (PTH) level in patients with chronic kidney disease (CKD) stages 4
      and 5. We retrospectively studied 138 patients with CKD stages 4 and 5 selected
      from the database of the Sheffield Kidney Institute in the interval from 1996 to
      2005. All patients had baseline as well as follow-up levels of PTH, adjusted
      serum calcium, phosphate, calcium phosphorus product, albumin, bicarbonate and
      estimated glomerular filtration rate (eGFR). At baseline, serum albumin, eGFR and
      adjusted serum calcium levels significantly negatively correlated with PTH serum
      levels. Adjusted serum calcium levels at last follow-up remained a significant
      negative predictor of PTH levels; however, baseline PTH levels demonstrated a
      significant positive correlation with final serum PTH levels. This study high
      lights the significance of serum PTH levels at presentation on the long-term
      effect of parathyroid gland function. This reinforces the need for early
      intervention to achieve optimal control of hyperparathyroidism in CKD patients.

PMID- 19587505
TI  - Stage of urinary bladder cancer at first presentation.
AB  - The stage of urinary bladder cancer is an important factor in determining
      prognosis of the disease. This prospective study was performed to determine the
      stage of bladder cancer at first presentation at the Rizgary Hospital in the
      Erbil governorate in Iraqi Kurdistan. We evaluated 72 patients with bladder
      cancer. The grades and stages of bladder cancer of these patients were determined
      through physical examination and investigations. We found that 47.2% of patients
      had superficial cancer, 19.4% had tumor with invasion into the lamina propria and
      30.6% of patients had tumor with invasion to muscle wall. Regional or distant
      metastases were found in 2.8% of patients. Well differentiated tumor was seen in
      44.4% of the patients, moderately differentiated tumor was found in 38.9% and
      poorly differentiated tumor was found in 16.7% of the patients. Our study
      suggests that bladder cancer is diagnosed at a relatively early stage in the
      Erbil governorate. However, the situation can be further improved by adopting
      proper screening programs and performing appropriate investigations.

PMID- 19587506
TI  - Early markers of renal injury in predicting outcome in thermal burn patients.
AB  - Acute renal failure (ARF) is a well known complication of severe burn and is an
      important factor that can increase mortality. To determine the predictors of
      acute renal failure that occur in major burns, we studied 40 patients with
      moderate to severe thermal burn injury - second to third degree with > 20% of
      total body surface area. All patients were subjected to routine investigations
      including: Serum creatinine, blood urea nitrogen, fractional excretion of sodium,
      urinary malondialdehyde and microalbuminuria on day 0, 3, 7, 14 and 21 of
      hospitalization. Nine patients (22.5 %) developed acute renal failure; 4 patients
      required supportive dialysis. The group that developed ARF showed an increase of
      markers of glomerular damage with appearance of micro-albuminuria on day 0 that
      reached 3 - 4 folds above its normal level on day 14 and remained constant with
      elevated serum creatinine and burn size in the 3 rd week of ARF, and progressed
      to overt proteinuria in 3 cases. Urinary malondialdehyde increased 3 folds above
      normal values before developing acute renal failure, and gradually increased on
      day 14, which coincided with the increased of microalbuminuria. Two cases (22.2%)
      in the ARF group who developed septicemia and required dialysis died on the 32 nd
      and 36 th days post-burn. Burn size and occurrence of septicemia were the only
      predictors of acute renal failure using multiple regression analysis (P value <
      0.001 and < 0.0371, respectively). We conclude that acute renal failure
      complicates burn patients and is related to the size and depth of burn and
      occurrence of septicemia. Microalbuminuria and urinary malondialdehyde are useful
      markers for prediction of renal outcome in such group of patients.

PMID- 19587507
TI  - The effect of increasing blood flow rate on dialysis adequacy in hemodialysis
      patients.
AB  - Inadequacy of dialysis is one of the determinants of morbidity and mortality in
      patients undergoing dialysis. The aim of this study was to assess the effect of
      increasing blood flow rate during hemodialysis (HD) on the adequacy of dialysis.
      In this study, 42 patients on maintenance HD were assessed. Body weight and blood
      urea nitrogen (BUN) levels before and after HD sessions were recorded on all the
      study patients. Volume of ultrafiltration, the duration of dialysis, percentage
      of filter clearance and flow rate of the dialysate were collected and documented
      in a checklist. Both Kt/V and urea reduction ratio (URR) were determined at two
      different blood pump speeds, i.e. 200 and 250 mL/min. During HD, hemodynamic
      status and vital signs of patients were monitored and controlled. After
      collecting the necessary data, efficiency of dialysis was calculated using the
      standard formula. Descriptive and analytical statistics was carried out to
      analyze the data. Using blood flow rate of 200 mL/min, 16.7% of patients had Kt/V
      higher than 1.3 and URR higher than 65. On the other hand, with flow rate of 250
      mL/min, 26.2% of patients had Kt/V higher than 1.3 and 35.7% of subjects had URR
      higher than 65. Paired t-test with 95% confidence showed a significant difference
      in dialysis efficiency between two groups. Our data further confirm that
      increasing the blood flow rate by 25% is effective in increasing dialysis
      adequacy in HD patients.

PMID- 19587508
TI  - Is pulmonary histoplasmosis a risk factor for acute renal failure in renal
      transplant recipients?
AB  - Prolonged use of immunosuppressive medication is associated with an increased
      susceptibility to viral, bacterial and fungal infections. This paper reports a 42
      year old kidney transplant recipient with 10 years of stable allograft function
      who developed pulmonary histoplasmosis and consequently lost his kidney. This
      report corroborates the previously proposed threat of infection with H.
      capsulatum for kidney allograft rejection.

PMID- 19587510
TI  - Tri-filial presentation of familial tuberous sclerosis with renal tumors.
AB  - Tuberous sclerosis is a rare neuro-cutaneous syndrome with autosomal dominant
      penetrance. Only some organs are involved, e.g., skin (earthy skin thickenings,
      ash leaf patches), cerebral cortex (hamartomatous nodules) and kidneys,
      (angiolipoma, adenocarcinoma). These hamar-tomatous swellings resemble potatoes
      and hence, referred to as tubers. We herein report on three patients (all
      familial), father, son and granddaughter, with this rare involvement, from the
      eastern part of India. The father and son had involvement of only the skin (i.e.
      nose) and kidneys while the disease penetrated further in the subsequent filial
      generations with son and granddaughter having skin, brain and bilateral kidney
      involvement. This kind of tri-filial progression has not till date, been reported
      from this region, making it an interesting case presentation.

PMID- 19587509
TI  - Post transplant anaplastic large T-cell lymphoma.
AB  - Post transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of
      lymphoid proliferation that ranges from polyclonal hyperplasia to monoclonal
      malignant lymphoma. We report a 13-year-old boy who was diagnosed with PTLD in
      February 2007 after 3 1/2 years of deceased renal transplantation. We treated him
      with an adapted ACVBP (doxorubicin, cyclo-phosphamide, vincristine, bleomycin and
      prednisone) regimen. He responded well to the chemo-therapy without deterioration
      of graft function.

PMID- 19587511
TI  - Short course of cyclophosphamide therapy may reduce recurrence in patients with
      tubulointerstitial nephritis and uveitis syndrome.
AB  - We report a 43-year-old woman with tubulointerstitial nephritis and uveitis
      syndrome (TINU syndrome) presented with a 5-day complaint of chills and fever,
      anorexia, nausea, and vomiting. She had elevated BUN and creatinine and
      urinalysis revealed decreased concentration, proteinuria, hematuria, and pyuria.
      A kidney biopsy showed non-caseating granulomatous tubulointerstitial nephritis.
      She suffered from anterior uveitis one month before, which was managed with local
      ophthalmic steroids. She received two months of oral high dose prednisolone,
      which was tapered over the next two months, and two months of 2 mg/kg
      cyclophosphamide. Her renal function recovered during the first two months. Her
      kidney and ocular symptoms did not recur during one year of follow-up. We suggest
      short course of cyclophosphamide and prednisolone for treatment of TINU syndrome
      to decrease the recurrence of kidney and ocular involvement.

PMID- 19587512
TI  - Neo-bladder vaginal fistula: an unusual complication after orthotopic urinary
      diversion.
AB  - Development of neo-bladder vaginal fistula is not an unknown complication after
      cystectomy and orthotopic urinary diversion in females. Compared to native
      bladder, the wall of the neo-bladder is much thinner that may render it
      vulnerable to fistulization. Injury to the vagina during cystectomy is the most
      important predisposing factor. Herein, we present a case of neo-bladder vaginal
      fistula and discuss the potential surgical and clinical factors contributing to
      its occurrence as well as the treatment options available.

PMID- 19587513
TI  - Pronase-free B-cell flow-cytometry crossmatch.
AB  - Detection of anti-class II antibodies by panel response assay (PRA) and flow
      cross-match techniques carries an important value in terms of graft function.
      Even low levels of pre-formed alloantibodies to HLA class II antigens represent a
      risk of rejection. We present here a method for blocking non-specific flow
      crossmatch reactions using pooled, heat-inactivated rabbit serum. This method
      shows very low background and minimal non-specific reactions. In addition, it
      avoids the use pronase enzyme that can non-specifically digest different cell
      surface proteins.

PMID- 19587514
TI  - Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis
      patients.

PMID- 19587515
TI  - Hypothermia in summer of Saudi Arabia with end stage renal failure suffering from
      diabetic nephropathy and malnutrition.

PMID- 19587517
TI  - Diabetic nephropathy with crescentic GN.

PMID- 19587516
TI  - Polyorchidism in a patient with azoospermia.

PMID- 19587518
TI  - Hyponatremia, rhabdomyolysis and acute kidney injury.

PMID- 19587519
TI  - Cost of hemodialysis in Iran.

PMID- 19587520
TI  - Infection-free hemodialysis: can it be achieved?
AB  - Infection is the second most common cause of mortality in patients with end stage
      re-nal disease (ESRD). Following strict aseptic precautions during a hemodialysis
      (HD) session could reduce dialysis-related infection, thereby reducing mortality
      and morbidity rates. This retrospective study was undertaken to identify the
      prevalence of dialysis-related bacteremia, sepsis, and catheter infections during
      HD at Bahrain Specialist Hospital, Bahrain, after following rigid infection
      control procedures. All HD sessions performed between January 2004 and December
      2007 were included. Strict aseptic precautions were observed for every patient in
      our dialysis unit. The patients' demographic characteristics as well as presence
      of hypertension (HTN), diabetes mellitus (DM) and use of immunosuppressive drugs
      were recorded. Results of culture of dialysis catheter tip were collected for all
      catheters removed or changed during the study period. Catheter surface culture
      yielding more than 15 colonies and catheter lumen culture yielding more than 1000
      CFU/mL were considered positive. All episodes of rigors, chills, bacteremia, and
      sepsis were recorded. Overall, a total of 1084 HD sessions performed on 46
      patients were studied. The mean age of the study patients was 55.2 years (SE
      2.5). Fifty four percent were male, 50% had DM, 85% had HTN and 11% were
      immunosuppressed. With implementation of strict aseptic precautions no catheter
      related infection, bacteremia or sepsis was found. Culture of 50 dialysis
      catheters showed Diptheroid in three patients, MRSE in two patients and MSSE,
      Enterobacter, and Klebsiella in one patient each. None of the study patients had
      signs or symptoms of infection or bacteremia. Our study further indicates that
      following strict aseptic precautions during HD sessions can reduce, if not
      eliminate, infection as a major cause of mortality and morbidity.

PMID- 19587521
TI  - Prevalence of hepatitis C and B infection and HC V genotypes among hemodialysis
      patients in Khuzestan province, southwest Iran.
AB  - Hepatitis B (HBV) and C (HCV) virus infection are the most important infections
      transmitted by the parenteral route in hemodialysis patients. This study is the
      first report of prevalence of viral hepatitis and hepatitis C virus genotypes in
      southwest Iran among hemodialysis patients. A cross-sectional study was carried
      out among 214 hemodialysis patients of the Central hemodialysis unit, from March
      2005 to August 2006. Serum samples were tested for HBsAg and anti-HCV using
      specific enzyme linked immunoassay (ELISA) kits and confirmed by PCR (HBV) and RT
      PCR (HCV). HCV genotypes were determined with HCV genotype specific primers using
      HCV genotype kit. Out of 214 hemodialysis patients, 34 were positive for anti-HCV
      (7.9%, 95% CI: 4.32-11.56) and 11 for HBsAg (5.1%, 95% CI: 2.18-8.1). The
      duration of treatment by hemo-dialysis was significantly associated with HBV and
      HCV positivity (P< 0.001). The predominant HCV genotype in the region was 1a
      (41.1%, 7/17), whilst genotypes 3a and 1b were found in 35.2% (6/17) and 23.5%
      (4/17) subjects, respectively. In conclusion although anti-HCV and HBsAg
      positivity in hemodialysis patients in Khuzestan province are smaller than those
      found in some other Iranian provinces and neighboring countries, they are still
      high. Enforcement of universal precautions in infection control, routine testing
      of patients, and serial determination of hepatic enzymes should be the common
      practice in dialysis centers in Iran.

PMID- 19587522
TI  - The prevalence, risk factors and awareness of hypertension in an urban population
      of Kerala (South India).
AB  - To determine the prevalence and possible risk factors for hypertension and
      prehypertensive state in Trivandrum City of Kerala (South India) using Joint
      National Committee (JNC) VII criteria, a team of trained fourth year medical
      students conducted a 10% random household survey in certain wards of the City.
      Households were selected using a random start and interval and all the members
      above the age of 10 years were interviewed using a standard questionnaire. The
      blood pressure (BP) was measured twice in each participant and the mean value of
      the two measurements was taken. A total of 482 individuals (212 males and 270
      females) were interviewed in the survey. Overall prevalence of hypertension was
      47% (n = 226) with equal sex ratio; 109 (21.6%) had stage-I hypertension, 45
      (9.34%) had stage-II hypertension and 72 were taking drug treatment. Only 55
      (11.4%) individuals had normal BP, while 201 (41.7%) were prehypertensives. Only
      81 (16.8%) hypertensive patients were aware of their disease. Among the
      parameters such as dietary habits, physical activity, educational standards, salt
      intake, and diabetes mellitus, only high salt diet (P= 0.03) and diabetes
      mellitus (P= 0.004) had a significant association with hypertensive state. In
      conclusion, the prevalence of hypertension is high but the awareness is low in
      our community, and intervention is necessary to impose control measures and to
      improve awareness.

PMID- 19587523
TI  - Prevalence and molecular characterization of extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae in Riyadh, Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Reports on extended-spectrum beta-lactamases (ESBL)
      production by Enterobacteriaceae, and especially in Klebsiella pneumoniae, are
      few in Saudi Arabia. Therefore, we determined the prevalence of ESBL in K
      pneumoniae from Riyadh and characterized the predominant beta-lactamase gene in
      these isolates. METHODS: A total of 400 K pneumoniae samples were isolated from
      two hospitals in Riyadh during 2007 and screened for production of ESBL using
      ESBL-E-strips and combined disk methods. PCR assay was used to detect bla(TEM),
      bla(SHV), and bla(CTX-M) genes. RESULTS: Phenotypic characterization identified a
      high ESBL rate of 55% of K pneumoniae isolates. ESBL producing K pneumoniae were
      PCR positive for SHV, TEM and CTX-M beta-lactamase genes with prevalences 97.3%,
      84.1% and 34.1%, respectively. Within the CTX-M family, two groups of enzymes,
      CTX-M-1 and CTXM- 9-like genes were found with prevalences of 60% and 40%,
      respectively. CONCLUSIONS: This study confirms the high rate of ESBL in K
      pneumoniae clinical isolates in hospitals in Riyadh. This study demonstrates the
      worldwide spread of bla(CTX-M) genes. This first report of the presence of the
      bla(CTX-M) gene in clincial isolates in Saudi Arabia is evidence of the
      continuing worldwide spread of this gene.

PMID- 19587524
TI  - Left-sided Amyand hernia.

PMID- 19587525
TI  - Inhibition of p38alpha unveils an AMPK-FoxO3A axis linking autophagy to cancer
      specific metabolism.
AB  - Autophagy is an essential process for the maintenance of cellular and metabolic
      homeostasis. Indeed, it is required for the recovery of ATP-generating substrates
      in cells subjected to different types of stress insults. Thus, the activity of
      the autophagic machinery strongly depends on the metabolic status of the cell.(1)
      It has been proposed that this principle applies not only to normal, but also to
      cancer cells,(2) despite the profound differences in their metabolism. Cancer
      cells predominantly produce ATP through the constitutive activation of aerobic
      glycolysis, a process that generally relies on the stabilization and activation
      of the transcription factor HIF1alpha, which regulates the expression of
      glycolytic genes.(3) We recently showed that p38alpha is required to sustain the
      expression of HIF1alpha target genes, and that its inhibition causes a rapid drop
      in ATP levels in colorectal cancer cells (CRCs). This acute energy need triggers
      AMPK-dependent nuclear accumulation of FoxO3A and subsequent activation of its
      transcriptional program, leading to sequential induction of autophagy, cell cycle
      arrest and cell death. In vivo, pharmacological blockade of p38alpha has both a
      cytostatic and cytotoxic effect on colorectal neoplasms, associated with nuclear
      enrichment of FoxO3A and expression of its target genes p21 and PTEN.(4) Our data
      suggest that CRCs impaired in their glycolytic metabolism trigger autophagy as a
      reversible recovery mechanism and undergo cell cycle arrest; however, the
      persistence of the stress insults inevitably leads to cell death.

PMID- 19587526
TI  - Autophagy is not universally required for phosphatidyl-serine exposure and
      apoptotic cell engulfment during neural development.
AB  - Apoptosis and autophagy are physiological processes implicated in the maintenance
      of cell and tissue homeostasis. We took advantage of the existence of multiple
      phases of developmental cell death in the embryonic chick retina and of the
      availability of short-term organotypic retinal cultures to explore the possible
      relationship between apoptosis and autophagy during neural development. We
      examined retinas at embryonic day 5, an early stage at which cell death is
      related to eye morphogenesis and to retinal ganglion cell generation, as well as
      at embryonic day 9, when cell death is associated with neurotrophic support of
      the retinal ganglion cells. Exposure to 3-methyl-adenine, a classical inhibitor
      of autophagy, elicited a selective accumulation of apoptotic bodies in the
      dorsotemporal area of embryonic day 5 retinas where neurogenesis is taking place.
      This accumulation was correlated with a blockage of phosphatidyl-serine
      presentation and, consequently, with a lack of engulfment of the dying cells by
      their neighbors. In striking contrast, none of these phenomena were observed in
      association with cell death in the optic nerve and optic fissure at embryonic day
      5, or in embryonic day 9 retinas. Our data suggest that autophagy is essential
      for phosphatidyl-serine presentation by apoptotic cells during the phase of cell
      death associated to neurogenesis, but this is not a universal requirement for all
      phases of cell death occurring during retinal development.

PMID- 19587527
TI  - H1 subtype expression during cell proliferation and growth arrest.
AB  - H1 histone subtype genes differ in their expression patterns during the different
      stages of the cell cycle interphase. While the group of replication-dependent H1
      histone subtypes is synthesized during S phase, the replacement histone subtype
      H1.0 is also expressed replication-independently in non-proliferating cells. The
      present study is the first report about the analysis of the cell cycle-dependent
      expression of all five replication-dependent H1 subtypes, the replacement histone
      H1.0 and the ubiquitously expressed subtype H1x. The expression of these H1
      histone subtypes in HeLa cells was analyzed on mRNA level by quantitative real
      time RT-PCR as well as on protein level by immunoblotting. We found that after
      arrest of HeLa cells in G(1) phase by treatment with sodium butyrate, the mRNA
      levels of all replication-dependently expressed H1 subtypes decreased, but to
      very different extent. During S phase the individual replication-dependently
      expressed H1 subtypes show similar kinetics regarding their mRNA levels. However,
      the variations in their protein amounts partially differ from the respective RNA
      levels which especially applies to histone H1.3. In contrast, the mRNA as well as
      the protein level of H1x remained nearly unchanged in G(1) as well as during S
      phase progression. The results of the present study demonstrate that the cell
      cycle-dependent mRNA and protein expression of various H1 subtypes is
      differentially regulated, supporting the hypothesis of a functional
      heterogeneity.

PMID- 19587528
TI  - The candidate tuberculosis vaccine Mtb72F/AS02A: Tolerability and immunogenicity
      in humans.
AB  - Tuberculosis (TB) remains uncontrolled in many parts of the world and the
      development of an effective vaccine against TB represents a high priority unmet
      medical need. Healthy PPD (tuberculin purified protein derivative)-negative adult
      volunteers, aged 18-40 years received three doses of the candidate Mtb72F/AS02A
      vaccine according to a 0-1-2 months schedule in an open-label Phase I study
      (NCT00730795). Solicited, unsolicited and serious adverse events (AEs),
      hematological and biochemical laboratory parameters were assessed. Mtb72F
      specific humoral responses were assessed by ELISA and cell-mediated immune (CMI)
      responses by intracellular cytokine staining (ICS) and short-term ELISPOT assays.
      CMI responses to the component peptides (Mtb39a and the Mtb32a C- and N-terminal
      antigen domains, Mtb32C and Mtb32N) were also assessed by ICS. The Mtb72F/AS02A
      vaccine appeared to be mainly locally reactogenic but this was considered
      acceptable, since these AEs were usually transient and resolved within 1-2 days.
      Most AEs reported were mild in intensity, no serious AEs occurred, no medically
      significant biochemical or hematological abnormalities related to vaccination
      were measured and all AEs resolved without sequelae. The vaccine induced
      statistically significant changes in humoral and CMI response measures. The
      Mtb72F antigen induced good production of IL-2 and IFNgamma in the ELISPOT assay
      and CD4(+) T cells expressing at least two activation markers (mainly CD40-L and
      IL-2) were observed with ICS. A similar CMI profile was observed with Mtb39a and
      Mtb32N. The induced CMI responses persisted for at least 6 months post
      vaccination. All subjects were seropositive for anti-Mtb72F antibodies one month
      post-dose 2 and 6 months post-dose 3. This first trial in humans found
      Mtb72F/AS02A to have an acceptable tolerability, to be immunogenic in healthy
      adults and warrants further development of the vaccine.

PMID- 19587529
TI  - MUC2: a new key for pancreas cancer prognosis.

PMID- 19587530
TI  - Autophagy maintains cardiac function in the starved adult.
AB  - To examine the functional significance and detailed morphological characteristics
      of starvation-induced autophagy in the adult heart, we starved green fluorescent
      protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic
      mice for up to 3 days. Electron microscopy revealed that, after as little as 12
      hours of starvation, round and homogenously electron-dense lipid droplet-like
      vacuoles appeared in cardiomyocytes. These were determined to be lysosomes based
      on cathepsin D immunopositivity and acid phosphatase activity. The number of
      these lysosomes increased with starvation time, and typical autolysosomes with
      intracellular organelles destined for degradation appeared and increased in
      number at later times during the starvation period. Myocardial expression of the
      autophagy-related proteins LC3-II, cathepsin D and ubiquitin increased, while
      myocardial ATP content decreased, as the starvation interval proceeded. Treatment
      with bafilomycin A(1), an autophagy inhibitor, did not affect cardiac function in
      normally fed mice, but it significantly depressed cardiac function and caused
      significant left ventricular dilatation in the mice starved for 3 days.
      Cardiomyocytes from starved mice treated with bafilomycin A(1) showed marked
      accumulation of lysosomes, and the myocardial amino acid content, which increased
      during starvation in normally fed mice, as well as the myocardial ATP content,
      were severely reduced, which likely contributed to the cardiac dysfunction. The
      present findings suggest autophagy plays a critical role in the maintenance of
      cardiac function during starvation in the adult.

PMID- 19587531
TI  - Adenoviral mediated transduction of adenoid cystic carcinoma by human TRAIL gene
      driven with hTERT tumor specific promoter induces apoptosis.
AB  - Adenoid cystic carcinoma (ACC) is a common malignant tumor in salivary glands.
      Unfortunately, current treatment modalities which include surgery, radiation and
      chemotherapy have limited success rates. To develop new treatment strategies we
      hypothesized that a cancer-specific apoptotic ligand driven by a tumor specific
      promoter would specifically induce apoptosis in ACC. To test this concept, we
      selected tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the
      human telomerase reverse transcriptase (hTERT) promoter. The latter is highly
      active in 85% of human cancer cells while it is mostly inactive in somatic cells.
      Using immunohistochemistry we confirmed that ACC samples but not normal salivary
      cells were positive for hTERT. Similar results were also seen in an ACC cell
      line, SACC-83. We then constructed first generation Ad5 vectors which used the
      hTERT promoter to drive TRAIL (AdTERT-TRAIL). Transduction of SACC-83, but not of
      control human embryo-fibrocyte lung (HEL) cells, led to apoptosis as measured by
      MTT assay and flow cytomerty. We used the SACC-83 cells for a subcutaneous tumor
      model in vivo. Intratumoral injections of AdTERT-TRAIL (5 x 109 particles/tumor)
      but not of AdTERT-EGFP or PBS resulted in significant (p < 0.01) reduction in
      tumor sizes, which demonstrated that the human TRAIL driven by tumor-specific
      promoter could efficiently induce apoptosis in SACC-83 cells in vitro and in
      vivo. These results suggest that a novel gene therapy strategy can also be used
      in the treatment of ACC in the near future.

PMID- 19587533
TI  - Autophagy is required for tolerance of drought and salt stress in plants.
AB  - Autophagy is a protein degradation process in which cells recycle cytoplasmic
      contents when subjected to environmental stress conditions or during certain
      stages of development. Upon the induction of autophagy, a double membrane
      autophagosome forms around cytoplasmic components and delivers them to the
      vacuole or lysosome for degradation. In plants, autophagy has been shown
      previously to be induced during abiotic stresses including nutrient starvation
      and oxidative stress. In this paper, we demonstrate the induction of autophagy in
      high salt and osmotic stress conditions, concomitant with the upregulation of
      expression of an Arabidopsis thaliana autophagy-related gene AtATG18a. Autophagy
      defective RNAi-AtATG18a plants are more sensitive to salt and drought conditions
      than wild-type plants, demonstrating a role for autophagy in the response to
      these stresses. NADPH oxidase inhibitors block autophagy induction upon nutrient
      starvation and salt stress, but not during osmotic stress, indicating that
      autophagy can be activated by NADPH oxidase-dependent or -independent pathways.
      Together our results indicate that diverse environmental stresses can induce
      autophagy and that autophagy is regulated by distinct signaling pathways in
      different conditions.

PMID- 19587534
TI  - RNAi screen for therapeutic target in leukemia.

PMID- 19587535
TI  - Premature aging syndrome gene WRN genetically interacts with a topoisomerase.

PMID- 19587536
TI  - A combined proteomic and genetic analysis identifies a role for the lipid
      desaturase Desat1 in starvation-induced autophagy in Drosophila.
AB  - Autophagy is a lysosomal-mediated degradation process that promotes cell survival
      during nutrient-limiting conditions. However, excessive autophagy results in cell
      death. In Drosophila, autophagy is regulated nutritionally, hormonally and
      developmentally in several tissues, including the fat body, a nutrient-storage
      organ. Here we use a proteomics approach to identify components of starvation
      induced autophagic responses in the Drosophila fat body. Using cICAT labeling and
      mass spectrometry, differences in protein expression levels of normal compared to
      starved fat bodies were determined. Candidates were analyzed genetically for
      their involvement in autophagy in fat bodies deficient for the respective genes.
      One of these genes, Desat1, encodes a lipid desaturase. Desat1 mutant cells fail
      to induce autophagy upon starvation. The desat1 protein localizes to autophagic
      structures after nutrient depletion and is required for fly development. Lipid
      analyses revealed that Desat1 regulates the composition of lipids in Drosophila.
      We propose that Desat1 exerts its role in autophagy by controlling lipid
      biosynthesis and/or signaling necessary for autophagic responses.

PMID- 19587537
TI  - MUC2 but not MUC5 expression correlates with prognosis in radically  resected
      pancreatic cancer patients.
AB  - INTRODUCTION: Pancreatic cancer is one of the most aggressive gastrointestinal
      cancer with less than 10% long-term survivors. The apoptotic pathway deregulation
      is a postulated mechanism of carcinogenesis of this tumor. The present study
      investigated the prognostic role of MUC2 and MUC5 apomucin expression in a series
      of surgically resected pancreatic cancer patients. RESULTS: By univariate
      analysis, survival was influenced by MUC2 expression but not by MUC5 expression.
      The MUC2 overexpression was associated with better prognosis (p = 0.003). By a
      multivariate Cox regression analysis, MUC2 overexpression maintained the
      prognostic statistical value. In particular, patients with high MUC2 staining
      showed a longer survival. Moreover the present study does report the absence of a
      prognostic role of MUC5 expression in this type of cancer. MATERIAL AND METHODS:
      All patients affected by pancreatic ductal adenocarcinoma and treated with
      surgical resection from 1988-2003 were considered for the study. MUC2 and MUC5
      expression were evaluated by immunohistochemical staining. Tumor specimens of 59
      resected patients were included in the study. CONCLUSIONS: The study demonstrated
      the prognostic relevance of MUC2 expression in pancreatic cancer and underlined
      its potential role as target gene in the field of therapy research.

PMID- 19587538
TI  - Morphological homeostasis by autophagy.
AB  - With cellular organelles coming in all shapes and sizes, the principle 'form
      follows function' is readily discernible through the cytologist's lens.
      Architecturally, one might ask whether there is feedback in this organization.
      Does a cell 'know' when it has constructed membrane into the stacks of the Golgi,
      the cisternae of the mitochondria or the tubules of the endoplasmic reticulum?
      Proofreading can occur in vivo as both errors in nucleic acids and misfolds in
      proteins are recognized by the cell. Are there analogous systems which
      maintain/regulate the architectural integrity of organelles? Our recent paper
      entitled Generation of cubic membranes from controlled homotypic interactions of
      membrane proteins in the endoplasmic reticulum suggests that autophagy may play
      such a role.

PMID- 19587539
TI  - Measuring public health officers' opinions on new vaccination programs by means
      of the WHO Vaccine Introduction Guidelines.
AB  - A group of public health officers and gynecologists were requested to express
      their opinion on whether immunization for: HPV in girls older than 12 years,
      varicella with combined MMRV vaccine and rotavirus (RV) should be included in the
      National Immunization Plan in Italy. For each of the three immunization programs,
      a specific questions list was prepared following the eight steps of the WHO
      Vaccine Introduction Guidelines flowchart. For each immunization strategy, a
      logistic regression model was used to identify the set of topics which, jointly
      considered, showed the strongest influence on the final responder's statement.
      Eighty-seven responders (82% of which were public health officers) out of 127
      participants provided 247 evaluable questionnaires. The final statement "to
      introduce the vaccine" was voted by 83.5%, 77.9% and 52.4% for HPV, MMRV and RV,
      respectively. The public health priority, the burden of disease, the economic and
      financial issues and the vaccine presentation were the most relevant topics,
      however, the pattern was different among the three immunization strategies.

PMID- 19587540
TI  - A new means to deal with ends: Heat shock protein regulation of the DNA damage
      response protein Apollo.

PMID- 19587541
TI  - HPV E6 oncoprotein prevents recovery of stalled replication forks independently
      of p53 degradation.

PMID- 19587542
TI  - The COP9 signalosome-cyclosome connection.

PMID- 19587543
TI  - Catching chromatin relaxation in act by flow cytometry.

PMID- 19587544
TI  - Opening the treasure chest of miR-200s family members.

PMID- 19587546
TI  - Fear of commitment: Hes1 protects quiescent fibroblasts from irreversible
      cellular fates.
AB  - The cellular state of quiescence is characterized by an exit from the cell cycle
      that is reversible, that is, upon appropriate stimulation, quiescent cells can re
      enter the cell cycle, proliferate and produce progeny. In this way, quiescent
      cells can be distinguished from cells in an irreversibly arrested state such as
      senescence or terminal differentiation. The molecular basis for reversible versus
      irreversible cell cycle arrest is unclear. In a recent study, we demonstrated
      that the transcriptional regulator Hes1 has a role in maintaining fibroblasts in
      a reversible quiescent state: overexpression of Hes1 protects fibroblasts against
      senescence or differentiation, and inhibition of endogenous Hes1 makes quiescent
      fibroblasts more susceptible to these states. Here we describe the molecular
      mechanisms by which Hes1 regulates gene expression by modifying histone tails and
      thus affecting chromatin conformation. We put forward models for how Hes1 is
      regulated and how it protects quiescent cells from differentiation and
      senescence.

PMID- 19587545
TI  - Atypical BH3-domains of BNIP3 and BNIP3L lead to autophagy in hypoxia.
AB  - Normal and tumor cells subjected to a hypoxic microenvironment show evidence of
      autophagy. We hypothesize that cells will sense hypoxia as a warning signal to
      upcoming drastic microenvironmental conditions and that autophagy, acting as a
      survival mechanism, will provide time for cells to adapt. This work demonstrates
      for the first time that the atypical BH3-domain of BNIP3 and BNIP3L, two HIF
      target genes, can compete with Beclin 1-Bcl-2 and Beclin 1-Bcl-X(L) complexes,
      releasing Beclin 1 from the complex and then enhancing autophagy. We thus
      revealed a new role for BH3-only proteins in the cellular response to hypoxia.

PMID- 19587547
TI  - Multi-faceted regulation of mitochondria by TOR.

PMID- 19587549
TI  - Introduction: Reducing cardiovascular risk: ONTARGET--a new standard in
      cardiovascular protection.

PMID- 19587550
TI  - Effects of angiotensin II receptor blockers on diabetic nephropathy.
AB  - Impaired kidney function increases the risk of cardiovascular morbidity and
      mortality. Coexistence of hypertension and type 2 diabetes increases the risk of
      kidney damage, hypertension being an independent risk factor for kidney disease
      progression. Angiotensin II, through its inflammatory, proliferative, and
      thrombotic effects, adversely affects renal perfusion and increases oxidative
      stress, thus playing a pivotal role in kidney disease progression. Angiotensin II
      receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors
      improve markers of kidney disease and slow kidney disease progression in diabetic
      and nondiabetic patients; this kidney protection may be in addition to their
      antihypertensive activity in those with advanced proteinuric nephropathy. Key
      beneficial effects of ARBs and ACE inhibitors throughout the kidney disease
      continuum are primarily explained by blood pressure lowering effects and
      partially by their direct blockade of angiotensin II. Recent studies have shown
      that telmisartan, an ARB with high lipophilicity and the longest half-life
      compared with other ARBs, provides benefits on markers of cardiovascular risk,
      that is, microalbuminuria and slowing of early-stage nephropathy.

PMID- 19587551
TI  - Clinical evidence from ONTARGET: the value of an angiotensin II receptor blocker
      and an angiotensin-converting enzyme inhibitor.
AB  - The Heart Outcomes Prevention Evaluation study established the angiotensin
      converting enzyme inhibitor ramipril, versus placebo, for prevention of
      cardiovascular events in high-risk patients. The ONgoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial (ONTARGET) was later conducted in
      similar high-risk patients using multifactorial treatment to control
      hypertension, platelet aggregation, and dyslipidemia, while comparing ramipril,
      telmisartan, or their combination, without placebo. In ONTARGET, the first
      angiotensin II receptor blocker-based study to be performed in a broader
      population of patients without congestive heart failure and/or left ventricular
      hypertrophy/dysfunction, telmisartan provided cardiovascular protection that was
      noninferior to ramipril. However, greater blockade of the renin-angiotensin
      system, using their combination, was not superior to ramipril alone. Telmisartan
      was better tolerated than ramipril in this high-risk population: notably, the
      incidence of cough and angioedema was significantly lower with telmisartan alone.
      Thus, telmisartan provides comparable efficacy to ramipril with less adverse
      events, which may encourage patient compliance.

PMID- 19587552
TI  - Defining blood pressure goals: is it enough to manage total cardiovascular risk?
AB  - It is well established that lowering blood pressure (BP) in patients with
      hypertension is associated with cardiovascular protection. Therefore, BP goals
      have been defined by international hypertension guidelines (<140/90 mmHg; <130/80
      mmHg for patients with type 2 diabetes). However, the relationship of BP with
      prognosis is complex, and controlling office BP may not be enough to optimally
      manage total cardiovascular risk. It is becoming clear that out-of-office BP
      measurements have important prognostic value. In the observational Pressioni
      Arteriose Monitorate E Loro Associazioni study, the risk of cardiovascular death
      over 11 years was progressively higher with 10-mmHg increases in office, home, or
      ambulatory BPs. Smooth control of 24-h BP may be of even greater importance, as
      the early morning BP surge, nighttime BP, and BP variability are associated with
      significant risk. A further consideration in managing total cardiovascular risk
      is the need for multiple antihypertensive agents to control BP.

PMID- 19587553
TI  - Preventing stroke: the PRoFESS, ONTARGET, and TRANSCEND trial programs.
AB  - Renin-angiotensin system blockers have been shown to reduce stroke risk, partly
      independent of their blood pressure-lowering effect. The PReventiOn regimen For
      Effectively avoiding Second Strokes (PRoFESS) trial, ONgoing Telmisartan Alone
      and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan
      Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular
      Disease (TRANSCEND) recently showed potential benefits of the angiotensin II
      receptor blocker, telmisartan, in reducing secondary strokes. In PRoFESS, 20 332
      ischemic stroke patients were randomized to telmisartan 80 mg versus placebo and
      to two antiplatelets in a 2 x 2 factorial design. After a mean exposure of 2
      years, telmisartan showed a nonsignificant lower rate of recurrent stroke versus
      placebo [880 versus 934; hazard ratio 0.95; 95% confidence interval (CI) 0.86
      1.04]. In a post-hoc analysis, from 6 months, telmisartan significantly reduced
      the number of strokes versus placebo (533 versus 608; hazard ratio 0.88; 95% CI
      0.78-0.99; P = 0.042). In the stroke subgroup of ONTARGET, telmisartan 80 mg
      showed a trend toward reducing recurrent stroke versus ramipril 10 mg (hazard
      ratio 0.91; 95% CI 0.79-1.05). In the TRANSCEND study, 5926 patients who were
      intolerant to angiotensin-converting enzyme inhibitors were treated with 80 mg
      telmisartan or placebo. In a combined analysis of PRoFESS and TRANSCEND, the
      incidence of the composite of stroke, myocardial infarction, or vascular death
      was 12.8% for telmisartan versus 13.8% for placebo (hazard ratio 0.91; 95% CI
      0.85-0.98; P = 0.013).

PMID- 19587554
TI  - Cardiovascular protection: a breakthrough for high-risk patients?
AB  - Angiotensin II has diverse effects on cardiovascular structure and function, and
      hence drugs that inhibit the formation or activity of this peptide have attained
      a central position in the prevention of morbidity and mortality from
      cardiovascular causes. The recent ONgoing Telmisartan Alone and in combination
      with Ramipril Global Endpoint Trial (ONTARGET) has shown that, in patients with
      vascular disease or patients with diabetes who were at high risk of
      cardiovascular events, the angiotensin II receptor blocker telmisartan is
      noninferior to the angiotensin-converting enzyme inhibitor ramipril in preventing
      such events, despite the ONTARGET patients receiving better background preventive
      therapy than those enrolled in the earlier Heart Outcomes Prevention Evaluation
      (HOPE) study. In addition, telmisartan offers superior tolerability to that of
      ramipril. Moreover, the finding in this study that combination therapy with
      telmisartan and ramipril produced no further reduction in cardiovascular events
      than either drug alone, despite producing greater reductions in blood pressure,
      highlights the potential importance of endothelial effects of renin-angiotensin
      system blockade in cardiovascular protection.

PMID- 19587555
TI  - Achieving blood pressure goals: should angiotensin II receptor blockers become
      first-line treatment in hypertension?
AB  - The benefits of blood pressure control on the risks of major cardiovascular
      events are well established. In clinical trials conducted in patients with mild
      to-moderate hypertension, the angiotensin II receptor blocker (ARB) telmisartan
      has been shown to provide reduction of blood pressure throughout the 24-h dosing
      interval. Clinical trials have also demonstrated that ARBs are effective agents
      in reducing the risk of cardiovascular mortality, stroke, heart failure and new
      onset atrial fibrillation. Recently, the ONgoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial (ONTARGET) study established that
      telmisartan reduces morbidity and mortality in a broad cross-section of patients
      at high risk for heart and vascular events, to an extent similar to that of the
      angiotensin-converting enzyme inhibitor ramipril. In addition, ONTARGET
      demonstrated that telmisartan is somewhat better tolerated than ramipril.
      Attributes such as effective blood pressure lowering, tolerability and convincing
      outcomes data mean that ARBs satisfy the requirements for first-line
      antihypertensive agents.

PMID- 19587560
TI  - Keeping up with the latest.

PMID- 19587562
TI  - Body mass index (BMI) report cards: should schools be responsible for screening?

PMID- 19587561
TI  - Body mass index (BMI) report cards: should schools be responsible for screening?

PMID- 19587563
TI  - Facilitating attachment after international adoption.
AB  - Americans have increasingly turned to international adoption (IA) as an
      alternative way to build a family. Unfortunately, IA families are often being
      developed under conditions of loss, and sometimes these families struggle to form
      healthy attachments to each other. Disordered attachment (the failure to form a
      reciprocal, loving bond between parent and child) can occur, and can have
      devastating consequences. In some instances, IA children have been relinquished
      into state foster care systems; other families simply struggle for years caring
      for a developmentally delayed child who appears to have no emotion for his/her
      adoptive family. Nurses are likely to have contact with IA families and can use
      their education about attachment and bonding to help facilitate attachment in
      these developing families. Swanson's caring theory provides a clinically useful
      guide to meet this need.

PMID- 19587568
TI  - Formative infant feeding experiences and education of NICU nurses.
AB  - PURPOSE: To explore the formative infant feeding experiences and education of
      NICU nurses. STUDY DESIGN AND METHODS: An ethnography was undertaken over 14
      months in a level IV NICU in a free standing pediatric hospital in the
      Northeastern U.S. Purposeful sampling was used to select informants. General
      informants included 114 NICU nurses who were observed and informally interviewed
      an average of 3.5 times. Eighteen of these served as key informants and each was
      formally interviewed once with an additional average of 12 observations/informal
      interviews. Descriptions of feeding experiences and education were coded and
      analyzed for recurring patterns using NUD*IST software. FINDINGS: The NICU nurses
      identified a norm for formula feeding during their formative experiences as
      children. The nurses described increased exposure to varied feeding methods
      during their adulthood, but breastfeeding was often associated with difficulties
      among their families and friends. The nurses in this study recounted minimal
      exposure to breastfeeding in nursing school. The nurses' personal experiences
      with breastfeeding were laden with strong emotional reactions intertwined with
      their feelings about motherhood. CLINICAL IMPLICATIONS: Nurses' past experiences
      and education must be addressed if efforts are to be made to promote
      breastfeeding in the NICU. Breastfeeding education programs for nurses should
      include reflective components to help nurses identify structural barriers and
      reframe any negative personal experiences.

PMID- 19587565
TI  - Sexuality & breastfeeding: what do you know?
AB  - Sexual functioning in the postpartum period has been examined in the literature,
      but does not seem to be commonly discussed among practitioners. Clinicians
      involved in the care of pregnant and postpartum women may be unaware of how
      childbirth and breastfeeding influence sexual health; this could leave patients
      uninformed about potential changes that could affect their sexual functioning
      post-delivery. There is evidence that breastfeeding specifically elicits changes
      in sexuality. With the increased emphasis on breastfeeding in hospitals and
      society, all nurses should have a basic understanding about sexuality, and should
      provide teaching about this to their patients. This review discusses major sexual
      changes associated with breastfeeding, including specific hormonal and physical
      changes, as well as strategies for discussing issues of sexuality with patients.
      Examples are provided to help nurses initiate discussion about sexuality,
      breastfeeding, and sexual changes during the postpartum period.

PMID- 19587569
TI  - Debriefing to help perinatal nurses cope with a maternal loss.
AB  - The death of a mother in a perinatal unit is a devastating event for the family
      and for the perinatal staff. An unexpected maternal death may be considered a
      critical incident, requiring leadership to reflect on the emotional well-being of
      all the staff who were involved in the patient's care. In order to assist staff
      in coping with the impact of a maternal loss, the organization and leadership
      team can apply the principles of debriefing, during which an expert in crisis
      intervention works to help the group recognize both healthy and unhealthy coping
      skills, and follows up with affected individuals who require ongoing help. This
      article presents a review of different techniques of debriefing, applies
      debriefing to maternal loss, and provides a review of coping skills for nurses.
      The leadership team's support is essential to promoting healthy coping and
      emotional healing when a tragedy occurs on the perinatal unit.

PMID- 19587566
TI  - Hypoxia in the term newborn: part three--sepsis and hypotension, neurologic,
      metabolic and hematologic disorders.
AB  - Causes of hypoxia and cyanosis in the term newborn can be found within all
      physiologic systems and take the form of hundreds of specific diagnoses. In the
      first and second parts of this series, a wide range of cardiac and pulmonary
      causes for newborn hypoxia and cyanosis have been examined. Because they are
      familiar, cardiac and pulmonary diagnoses often represent our reactionary
      opinions-the options that we first entertain even before a proper systematic
      approach to the infant has been taken. In this final of a three part series,
      neurologic, hematologic and metabolic disorders are explored as a cause for
      abnormal oxygenation, as well as sepsis and hypotension. It is within these final
      categories that we find many of the obscure possibilities for neonatal hypoxia
      the diagnoses that often require rigorous testing, or more sophisticated
      laboratory interpretation. Without consideration of these elusive entities,
      however, appropriate treatment and referral will be unnecessarily delayed.

PMID- 19587570
TI  - Adolescent attitudes, beliefs, and concerns regarding breastfeeding.
AB  - PURPOSE: To investigate the attitudes, beliefs, and concerns of pregnant and
      postpartum adolescents regarding breastfeeding. STUDY DESIGN AND METHODS:
      Audiotaped focus groups of low-income, largely minority pregnant and postpartum
      adolescents were conducted and transcripts analyzed using content analysis
      techniques. FINDINGS: Major themes identified were in the area of beliefs, such
      as "They say" it's healthy, or "It hurts"; attitudes, such as breastfeeding is
      the mother's "choice" and "The baby comes first"; and concerns such as privacy,
      and "Breastfeeding leads to dependency." CLINICAL IMPLICATIONS: Adolescents can
      be encouraged to breastfeed, but require appropriate education beyond what they
      have heard from others. Myths such as pain during breastfeeding need to be
      addressed. Since teens want to learn but not be told what to do, active learning
      strategies such as guided Internet searches could be helpful to guide them into
      discovery of the benefits of breastfeeding. Since all the teens in this study
      felt that "the baby comes first," emphasizing the benefits of breastfeeding for
      the baby should predominate educational efforts. Concerns related to physical
      exposure while breastfeeding can be addressed antenatally through discussing
      creative strategies to maintain modesty. This study suggests that, in the
      postpartum hospital setting, adopting a sensitive, initially "hands-off' approach
      to supporting breastfeeding might be more well-accepted than tactile assistance,
      and that following the initial establishment of a milk supply, various levels of
      breastfeeding exclusivity should be considered as potentially acceptable infant
      feeding patterns.

PMID- 19587571
TI  - Error in vaccine article.

PMID- 19587572
TI  - Accurate assessment of mother & infant sleep: how many diary days are required?
AB  - PURPOSE: The purpose of the study was to determine the number of days of diary
      data collection needed to reliably measure mother and infant sleep-wake pattern.
      STUDY DESIGN AND METHODS: Twenty healthy adult mothers and their healthy term
      gestation infants age 4 to 10 weeks postnatal participated in a single group,
      cross-sectional design. Mothers completed a paper and pencil sleep-wake diary
      divided into 15-minute time periods. Data were collected in the home environment
      over a 4-day period. Mother and infant sleep and wake as well as infant feeding
      and cry were summarized and compared using between 1 and 4 days of data.
      Reliability was evaluated by correlating results obtained using from 1 to 4 days
      of data. RESULTS: Mean values for mother and infant sleep and activity variables
      did not differ significantly by day. Correlation among values calculated using
      increases in number of days of data showed adequate reliability (r > or = 0.80)
      when 3 days of data were used. CLINICAL IMPLICATIONS: Clinical measures should be
      valid and reliable. Due to day-to-day changes in maternal and infant sleep-wake
      pattern, a diary collected over 1 day may not provide adequate sleep information.
      These study findings indicate that 3 days of diary data are sufficient to
      reliably measure mother and infant sleep patterns. When using a diary to assess
      maternal and infant sleep-wake pattern in clinical practice or in clinically
      based research, a 3-day period is suggested.

PMID- 19587573
TI  - Melamine: the world at your doorstep.

PMID- 19587574
TI  - The American Recovery and Reinvestment Act: health information technology
      stimulus.

PMID- 19587582
TI  - Obstetrical triage: stable for discharge.

PMID- 19587575
TI  - So you want to make a difference in global health?

PMID- 19587583
TI  - Predictors of placebo response in a randomized, controlled trial of phytotherapy
      in menopause.
AB  - OBJECTIVE: The aim of this study was to evaluate predictors of the placebo
      response in a randomized, placebo-controlled, double-blind trial of a
      phytotherapeutic combination for the treatment of menopausal symptoms. METHODS: A
      post hoc analysis was conducted on data from 46 placebo participants completing
      the study. Variables at baseline were investigated for prediction of improvement
      on any of the endpoints of flushing, depression measured on the Hamilton
      Depression Inventory, and menopausal symptoms measured on the Greene Climacteric
      Scale. Hierarchical linear regression analyses were carried out on the individual
      endpoints, controlling for baseline scores. Multivariate linear regression
      analysis was also conducted on these three endpoints in combination. RESULTS:
      Higher anxiety at study entry predicted placebo response on all three outcome
      measures individually (flushing: R = 0.33, P = 0.03; depression: R = 0.34, P <
      0.001; and Greene Climacteric score: R = 0.24, P = 0.04); and in combination (P =
      0.002), as did total Greene Climacteric scores at study entry (R = 0.24, P =
      0.005). Improvement during nontreatment run-in predicted placebo response for
      depression (P = 0.005), menopausal symptoms (R = 0.28, P = 0.013), and the three
      combined endpoints (P = 0.015). Severity of scores at baseline predicted
      subsequent improvement on the Greene Climacteric scores only (r = 0.038, P =
      0.009). CONCLUSIONS: These findings may facilitate identification of potential
      placebo responders in future randomized controlled trials on menopausal symptoms
      and have relevance to study design in this context. Further research is required.

PMID- 19587584
TI  - Use of deep vein thrombosis prophylaxis in hospitalized cancer patients.
AB  - Venous thromboembolism is a common complication and a major cause of morbidity
      and mortality in cancer patients. Patients with malignancies have a four-fold
      greater risk of venous thromboembolism compared with patients without
      malignancies. Underuse of deep vein thrombosis (DVT) prophylaxis persists,
      despite guidelines supporting its use in hospitalized cancer patients. This study
      was conducted to evaluate the use of DVT prophylaxis and its appropriateness in
      hospitalized cancer patients. This retrospective study included cancer patients
      admitted to Rafik Hariri University Hospital, a tertiary referral center in
      Beirut, Lebanon, over 2-month period, who were hospitalized for at least 2 days.
      We evaluated the use of anticoagulants for DVT prophylaxis in the absence of
      contraindications for their use. The risk factor profiles of the patients were
      reported in addition to the choice of the anticoagulant and the use of mechanical
      prophylaxis in patients with contraindications to anticoagulation. One hundred
      and thirty patients were studied out of which 34 (26.2%) had contraindications to
      anticoagulation use. In addition, 21 patients out of 95 (22.1%) who qualified for
      DVT prophylaxis received pharmacologic DVT prophylaxis. Enoxaparin was the most
      frequently prescribed anticoagulant (76.2% of the patients). Of those who
      received anticoagulation, only 47.6% received appropriate agent and dose. Among
      patients with contraindications to anticoagulation, only three (8.8%) received
      mechanical devices as nonpharmacologic DVT prophylaxis. DVT prophylaxis in
      hospitalized cancer patients is significantly underutilized. Several options are
      available to increase physicians' awareness of the problem.

PMID- 19587585
TI  - Acidic-store depletion is required for human platelet aggregation.
AB  - Platelet stimulation with thrombin induces an elevation in cytoplasmic free
      Ca(2+) concentration ([Ca(2+)]c) due to Ca(2+) release from intracellular stores
      and entry from the extracellular medium. Two different intracellular Ca(2+)
      stores have been described in human platelets: the dense tubular system and the
      lysosomal-like acidic stores. In the present study, we investigated the
      contribution of the acidic stores in thrombin-induced platelet aggregation. We
      have found that platelet aggregation induced by thrombin is reduced in a Ca(2+)
      free medium. Discharge of the acidic Ca(2+) stores by treatment with the
      sarcoendoplasmic Ca(2+)-ATPase (SERCA)3 selective inhibitor 2,5-di-(tert-butyl)
      1,4-hydroquinone reduced thrombin-evoked platelet aggregation. In the presence of
      2,5-di-(tert-butyl)-1,4-hydroquinone, platelet aggregation induced by the
      protease-activated receptor (PAR)-1 and PAR-4 agonist peptides, SFLLRN and
      AYPGKF, respectively, was significantly reduced. In cells with depleted acidic
      stores, activation of GPIb-IX-V by thrombin resulted in reduced or no platelet
      aggregation in a medium containing 1 mmol/l Caor in a Ca(2+)-free medium,
      respectively. This finding suggests that Ca(2+) accumulation in the acidic Ca(2+)
      compartments is required for platelet aggregation induced by activation of the G
      coupled PAR-1 and PAR-4 thrombin receptors and, by the occupation of the leucine
      rich glycoprotein GPIb-IX-V and provide evidence supporting a functional role of
      the lysosomal-like acidic Ca(2+) stores in human platelets.

PMID- 19587586
TI  - New observations in postpartum ovarian vein thrombosis: experience of single
      center.
AB  - The diagnosis of postpartum ovarian vein thrombosis (POVT) has become more
      accurate since the introduction of modern imaging techniques. We performed a
      prospective study at a single Medical Center in order to define the incidence and
      risk factors for POVT. Thirteen consecutive women with POVT were enrolled during
      a period of 4 years. Each participant underwent a computerized tomography scan
      for diagnosis followed by a profile for congenital and acquired thrombophilia. A
      detailed history of pregnancy, labor and state after delivery was obtained within
      2 days of diagnosis while the patient was still hospitalized. The incidence of
      POVT was four of 30,749 vaginal deliveries, nine of 9604 cesarean deliveries and
      six of 906 twin deliveries by cesarean section. The odds ratio for developing
      POVT was 21.37 for twin delivery versus singleton and 7.2 for cesarean section
      versus vaginal delivery. Of the 13 women with POVT, infection was found in seven
      women (53%) and other clinical risk factors in four (30%). Only three (23%)
      participants were found to have thrombophilia and one developed POVT while on
      enoxaparin treatment. Our results suggest that the risk for maternal POVT is
      increased by cesarean section delivery of twins. It appears that investigations
      for thrombophilia are unnecessary when POVT is the sole manifestation of
      thrombosis.

PMID- 19587587
TI  - Cellular therapy to control tumor progression.
AB  - PURPOSE OF REVIEW: The term 'cellular immunotherapy to control tumor progression'
      summarizes the dream of generations of investigators who ideally want to target
      cancer by the most natural way, namely the immune system itself. A variety of
      different approaches have been published with emphasis on the use of T cells in
      adoptive immunotherapy. Therefore, we focused our review of the literature on T
      cells to control tumor progression. RECENT FINDINGS: Adoptive T cellular
      immunotherapy of malignant disease has been used for many different malignancies
      in a broad variety of different clinical settings and experimental approaches.
      Regarding currently available data, adoptive immunotherapy is particularly
      effective in hematological disorders and especially after allogeneic stem cell
      transplantation in the context of the graft-versus-tumor effect. One major
      problem of immunotherapy for solid tumors might be represented by an inadequate
      homing of specific cells to tumor tissue and further T-cell inhibitory function
      of tumor stroma. An optimization of tumor homing/invasion will be a prerequisite
      for the successful application of adoptive T-cell transfer in solid tumors to
      reach effects comparable to tumor-specific immune responses following allogeneic
      stem cell transplantation (graft-versus-tumor reactions). SUMMARY: In this
      review, we tried to present the most recent findings concerning the use of T
      cells in adoptive immunotherapy of malignant disease. Furthermore, we discuss
      some of the main problems of this therapeutic approach, which have evolved from
      both basic research and clinical experience over the last few years and which
      might represent the basics to optimize adoptive immunotherapy.

PMID- 19587588
TI  - New antiplatelet agents.
AB  - PURPOSE OF REVIEW: Cardiovascular events are still a major concern despite dual
      antiplatelet treatment with aspirin and clopidogrel. Moreover, recent
      developments that improved platelet inhibition were associated with increased
      bleeding complications, suggesting that personal dose adjustment might be needed.
      This review is dedicated to new developments in antiplatelet agents other than
      ADP P2Y12 receptor blockers, which are discussed in a separate article of this
      issue. RECENT FINDINGS: The thrombin receptor protease activable receptor-1
      antagonist SCH530348 and the thromboxane receptor antagonist terutroban are two
      promising agents that are now undergoing phase III clinical trials. Cilostazol, a
      phosphodiesterase III inhibitor, is currently tested in phase IV trials for
      several new indications. Despite previous disappointing results with oral
      GPIIbIIIa antagonists, new compounds with unique features are under development.
      In addition, targeting intracellular signaling pathways is a new area of
      research, with several attractive targets. SUMMARY: Recent development of new
      antiplatelet agents, including inhibitors of thrombin receptor, thromboxane
      receptor, phosphodiesterase, glycoprotein VI, GPIIbIIIa and signaling pathways,
      may lead to a more effective and yet safe antiplatelet therapy with an improved
      clinical outcome.

PMID- 19587590
TI  - Emerging clinical issues in refugees.
AB  - PURPOSE OF REVIEW: The world's population is becoming increasing mobile. Each
      mobile population (e.g. immigrants, refugees, travelers) has certain
      characteristics that determine public health risk and infectious disease burden.
      Refugees present unique challenges to public health officials and infectious
      disease specialists. RECENT FINDINGS: Refugee migration to the United States
      represents the most controlled population movement between countries from a
      health perspective. Medical screening and programs that provide presumptive
      treatment for highly prevalent infectious diseases both prior to and after
      migration alter the infectious disease epidemiology in these populations.
      SUMMARY: Infectious disease specialists must recognize that different
      characteristics of distinct mobile populations will alter infectious disease
      burden. This article specifically highlights how recent public health approaches
      have altered the epidemiology and clinical presentation of malaria, intestinal
      parasites and tuberculosis in refugee populations.

PMID- 19587589
TI  - Treatment of cryptococcal meningitis in resource limited settings.
AB  - PURPOSE OF REVIEW: Cryptococcal meningitis most commonly occurs in advanced HIV.
      Although diminishing in the developed world with antiretroviral therapy (ART), it
      remains a major problem in resource-limited settings. ART rollout will improve
      long-term HIV survival if opportunistic infections are effectively treated.
      Considering cryptococcal meningitis in that context, this review addresses excess
      morbidity and mortality in developing countries, treatment in areas of limited
      drug availability and challenges posed by combined anticryptococcal and HIV
      therapy. RECENT FINDINGS: From Early Fungicidal Activity (EFA) studies,
      amphotericin B-flucytosine is best induction therapy but often unavailable; high
      dose amphotericin B monotherapy may be feasible in some settings. Where
      fluconazole is the only option, higher doses are more fungicidal. Serum
      cryptococcal antigen testing may identify patients at highest disease risk and
      primary prophylaxis is effective; the clinical role of such interventions needs
      to be established. Timing of ART introduction remains controversial; early
      initiation risks Immune Reconstitution Disease (IRD) delays may increase
      mortality. SUMMARY: Amphotericin B based treatment is appropriate where possible.
      More studies are needed to optimize fluconazole monotherapy doses. Other research
      priorities include management of raised intracranial pressure, appropriate ART
      initiation and IRD treatment. Studies should focus on developing countries where
      problems are greatest.

PMID- 19587592
TI  - Anal cancer prevention in HIV-positive men and women.
AB  - PURPOSE OF REVIEW: The incidence of human papillomavirus-associated anal cancer
      is unacceptably high among HIV-positive men who have sex with men, and possibly
      in HIV-positive women. Unlike most other malignancies occurring in the HIV
      positive population, anal cancer is potentially preventable, using methods
      similar to those used to prevent cervical cancer in women. This review discusses
      the issues around screening to prevent anal cancer. RECENT FINDINGS: Recent
      studies show that the incidence of anal cancer has increased since the
      introduction of highly active antiretroviral therapy in this population and now
      exceeds the highest incidence of cervical cancer among women reported anywhere in
      the world. SUMMARY: The high incidence of anal cancer among HIV-positive
      individuals must not be ignored, since it may be preventable. Given the current
      evidence and analogy with the cervical cancer prevention model, many clinicians
      believe that identification and treatment of high-grade anal intraepithelial
      neoplasia to prevent anal cancer are warranted. When the expertise to do so
      exists, this is a reasonable approach, particularly if coupled with efforts to
      optimize further screening and treatment approaches, as well as efforts to
      document the efficacy of high-grade anal intraepithelial neoplasia treatment to
      reduce the incidence of anal cancer.

PMID- 19587591
TI  - Targeting the Warburg effect in hematological malignancies: from PET to therapy.
AB  - PURPOSE OF REVIEW: To highlight key studies providing rationale for and utility
      in targeting glycolysis for the treatment of hematological malignancies. RECENT
      FINDINGS: Several therapeutic strategies are capitalizing on the diagnostic
      utility of 18fluoro-deoxyglucose positron emission tomography that relies on
      increased glycolysis and glucose utilization in tumor cells. Although aerobic
      glycolysis was initially proposed by Warburg to be due to mitochondrial
      impairment, recent studies have shown a preferential switch to glycolysis in
      tumor cells with functional mitochondria. Increased glucose consumption can be
      advantageous for a tumor cell through stimulation of cellular biosynthetic,
      energetic, and pro-survival pathways. We now have a greater appreciation for the
      utilization of glucose in specific metabolic pathways that in some aspects can be
      complemented with other nutrients such as glutamine. Targeting glucose
      consumption for the treatment of hematological malignancies seems to be a
      promising field that will require characterization of tumor cell specific targets
      to inhibit glucose uptake and/or glycolysis. It is imperative to further our
      understanding of the tumor cell metabolome to target cellular bioenergetics in
      the treatment of cancer. SUMMARY: Targeting the glycolytic pathway for the
      treatment of hematological malignancies has sufficient rationale given the
      utility of fluoro-deoxyglucose positron emission tomography in diagnostic
      imaging. Further research is required in developing tumor cell specific
      therapeutics.

PMID- 19587593
TI  - Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV
      infection.
AB  - PURPOSE OF REVIEW: Oral human papillomavirus (HPV) infection is the principal
      cause of a distinct form of oropharyngeal cancer (OPCA) that has been rising in
      incidence in the United States since 1973, particularly among young men. The
      possible contribution of the HIV-epidemic to this increase is unclear. RECENT
      FINDINGS: Incidence rates for HPV-related OPCA increased with age and were
      strongly influenced by year of birth in the United States (cohort effect).
      Persons with HIV/AIDS are at increased risk ( approximately two to six-fold) for
      OPCA relative to the general population. However, this excess risk may be
      attributable to tobacco smoking rather than the three-fold higher prevalence of
      oral HPV infection in this population. Consistent with a viral attribution,
      however, is the apparent increase in risk of OPCA with severity of AIDS-related
      immunosuppression. Analogous to other HPV-related cancers (e.g. cervical and anal
      cancer), trends over time do not appear to be influenced by highly active
      antiretroviral (HAART) therapy. SUMMARY: Healthcare providers may encounter HPV
      related OPCA more frequently among individuals with HIV/AIDS as this population
      ages and due to the strong birth cohort effects observed in the general
      population. However, there is no evidence in support of different incidence
      trends over time among persons with and without HIV/AIDS.

PMID- 19587594
TI  - Managing menopausal symptoms after gynecological cancer.
AB  - PURPOSE OF REVIEW: As the length of survival in patients with gynecological
      malignancies increases due to advances in early diagnosis and therapy, quality of
      life becomes a major issue for the survivors. These women frequently suffer
      symptoms following an iatrogenically induced menopause. Many gynecologists advise
      these patients against hormonal replacement therapy. This review attempts to
      provide the clinician with information based on current evidence. RECENT
      FINDINGS: The most recent two prospective studies did not find an increase in the
      recurrence rates in endometrial cancer patients who used hormonal replacement
      therapy. To date, there are few studies on hormonal replacement therapy in
      patients with ovarian cancer but the available data suggest that there is no
      detriment to overall or disease-free survival. There are no data showing an
      association between poorer outcome and hormonal replacement therapy use in
      patients with cervical or vulvar cancers. SUMMARY: There is no evidence showing
      hormones negatively influence survival after treatment for epithelial ovarian,
      squamous cervical or vulvar cancer. Their use can be considered in symptomatic
      patients with endometrial cancer, after weighing the benefits against the risk of
      recurrence. Gynecologic cancer survivors suffering from menopausal symptoms
      should be supported by advice about the alternatives to hormonal replacement
      therapy and by giving them nonbiased information on the present knowledge on the
      effects of hormonal use in women with a previous cancer. It is reasonable to
      prescribe hormonal replacement therapy to symptomatic, well informed patients.

PMID- 19587596
TI  - Genetics of age-related macular degeneration.
AB  - PURPOSE OF REVIEW: Age-related macular degeneration (AMD) was until recently
      viewed as a part of the normal aging process; however, we are increasingly aware
      that genetic factors play a much greater role than previously suspected. This
      review will provide an up-to-date snapshot of the genetics of AMD to help guide
      our thoughts about its causes and the risk for family members. RECENT FINDINGS:
      Epidemiological research and basic bench research have identified pathways of
      oxidative stress, lipid metabolism and inflammation as playing causative roles in
      the pathogenesis of AMD. Emerging research is focusing on the biology of the
      retinal pigment epithelium as secreting pro and anti-inflammatory mediators in
      the eye. Antivascular endothelial growth factor therapy has dramatically improved
      the prognosis for neovascular or wet AMD patients. Nutritional supplementation
      with antioxidants and omega-3 fatty acids has provided treatment options for
      patients with atrophic or dry AMD. We should expect that some of the response to
      therapy might be genetically determined. SUMMARY: First-degree relatives of
      patients with AMD tend to have a higher risk of AMD. Recognizing an inherent
      genetic risk of AMD in these patients will improve their management and
      potentially help prevent blindness.

PMID- 19587597
TI  - Childhood macular dystrophies.
AB  - PURPOSE OF REVIEW: The aim of this review is to highlight recent advances in our
      understanding of the molecular genetic basis and phenotype of childhood onset
      macular dystrophies and to summarize current attempts to develop novel therapies
      for this group of disorders. RECENT FINDINGS: The genes associated with the major
      causes of childhood onset macular dystrophies have now been identified and
      current research efforts have been focused on understanding the function of the
      encoded protein, how the mutant protein leads to photoreceptor cell death and
      investigation of the range of retinal phenotypes that result from mutations in
      these genes. Assessment of the phenotype has been greatly helped by improvements
      in retinal imaging such as spectral domain optical coherence tomography and
      fundus autofluorescence imaging. The development of animal models has, despite
      their limitations, helped understanding of disease mechanisms and allowed
      assessment of new therapeutic approaches such as gene replacement therapy and
      pharmacological treatments. SUMMARY: Molecular diagnosis and improvements in
      retinal imaging have greatly improved the accuracy of diagnosis in paediatric
      macular disease and allowed better genetic counselling and information about
      prognosis to be given to children and their families. Advances in basic
      understanding of disease mechanism will lead to the development of clinical
      trials of novel therapies in the near future.

PMID- 19587595
TI  - Myopia genetics: a review of current research and emerging trends.
AB  - PURPOSE OF REVIEW: Myopia, or nearsightedness, is the most common human eye
      disorder in the world and is a significant global public health concern. Along
      with cataract, macular degeneration, infectious disease, and vitamin A
      deficiency, myopia is one of the most important causes of visual impairment
      worldwide. Severe or high-grade myopia is a leading cause of blindness because of
      its associated ocular comorbidities of retinal detachment, macular choroidal
      degeneration, premature cataract, and glaucoma. Ample epidemiologic and molecular
      genetic studies support heritability of the nonsyndromic forms of this condition.
      RECENT FINDINGS: Multiple myopia genetic loci have been identified, establishing
      this entity as a common complex disorder and underscoring the suitability for
      gene inquiry studies. Animal model research, primarily using form-deprivation
      techniques, implicates multiple altered regulation of biological substances in
      the ocular wall layers, which provides important information for prioritizing
      human candidate gene studies. Recent epidemiologic work supports a greater role
      for outdoor activity in relieving myopia progression rather than the previous
      touted young-age near-work activity model. SUMMARY: The identification of myopia
      susceptibility genes will not only provide insight into the molecular basis of
      this significant eye disorder, but will also identify pathways involved in eye
      growth and development. This effort may lead to effective therapies to treat or
      potentially prevent this common eye condition.

PMID- 19587598
TI  - Ethical issues in ocular genetics.
AB  - PURPOSE OF REVIEW: To review some of the major issues in ophthalmic genetics
      ethics: predictive testing, prenatal testing and abortion, gene therapy,
      confidentiality, payment for genetic testing, the duty to recontact patients and
      convey new information. RECENT FINDINGS: Patients and families may perceive
      benefits even though genetic testing may be associated with adverse psychosocial
      outcomes. Most patients were in favor of prenatal diagnosis but opposed abortion.
      Patient selection as candidates for gene therapy should be based on the different
      clinical characteristics of each hereditary disease. The balance between the
      right of the patient for confidentiality and the best interest of family members
      or society is an ethical challenge. Most insurance companies will pay for genetic
      testing if the condition is hereditary. The duty to recontact patients when new
      medical information becomes available is still ethically controversial. SUMMARY:
      The field of ocular genetics is ever growing involving complex medical,
      technical, financial and social issues. As a result, ethical issues are expected
      to become more common. Properly prepared medical professionals as well as unique
      counseling for participants and families may enable improved decision-making
      taking into consideration the needs of each individual.

PMID- 19587599
TI  - Recent advances in retinoblastoma genetic research.
AB  - PURPOSE OF REVIEW: Retinoblastoma is a pediatric eye tumor that serves as a
      paradigm for understanding the genetic basis of cancer. This review will
      highlight recent advances in retinoblastoma genetic research and discuss how
      these new findings influence our knowledge of retinoblastoma tumorigenesis and
      management. RECENT FINDINGS: Current data demonstrate that retinomas, benign
      retinal tumors found in some retinoblastoma patients, exhibit bi-allelic
      mutations in RB1, the retinoblastoma gene, and lack of expression of the
      retinoblastoma protein. Interestingly, retinomas demonstrate a low level of
      genomic instability that becomes progressively more severe in retinoblastoma
      tumors. Additionally, a subset of retinomas share genomic alterations with
      retinoblastoma. Collectively, these data suggest that retinomas represent true
      premalignant lesions and not regressed retinoblastoma tumors, as previously
      thought. Translational advances in retinoblastoma genetic research include
      development of an allele-specific assay that now enables the identification of
      mutational mosaicism, thereby increasing the rate of RB1 mutation detection in
      bilaterally affected patients to as high as 95%. SUMMARY: These and related
      research efforts reveal novel data that enhance our understanding of the biology
      of retinoblastoma. These observations may facilitate new therapeutic approaches
      to further decrease the morbidity and mortality associated with retinoblastoma
      and other more common forms of cancer.

PMID- 19587600
TI  - Management of canalicular obstructions.
AB  - PURPOSE OF REVIEW: The successful treatment of canalicular obstructions continues
      to represent a therapeutic challenge. Conjuctivodacryocystorhinostomy with a
      Lester Jones bypass tube is the standard treatment in these situations. Although
      a high rate of anatomic success can be achieved with this procedure, a relatively
      high rate of complications and poor patient satisfaction have been reported.
      Because of this, alternative techniques have emerged. Herein, we review all these
      techniques described in the literature. RECENT FINDINGS: Increasing interest in
      minimally invasive surgery and developments in fiberoptic technology have fueled
      advances in endocanalicular surgery. Canalicular trephination for obstructions at
      any level of the canalicular system and laser and balloon canaliculoplasty for
      focal canalicular and common canalicular stenoses may offer a well tolerated,
      fast and easy alternative, with potentially better patient satisfaction when
      compared with conjuctivodacryocystorhinostomy. SUMMARY: The alternative
      techniques to conjuctivodacryocystorhinostomy are less invasive, and respect and
      utilize any healthy and functional part of the canalicular system. The correct
      choice of the technique for a given canalicular obstruction, and therefore the
      long-term success, depends on the site and degree of the obstruction.

PMID- 19587601
TI  - Assessing overall duration of cardiovascular medicines in veterans with
      established cardiovascular disease.
AB  - BACKGROUND: This study aimed to determine persistence, adherence, and time
      without therapy with cardiovascular medicines over all episodes of use among
      veterans following hospitalization for ischemic heart disease. METHODS:
      Retrospective cohort study using Department of Veterans' Affairs database
      including 9635 veterans with a hospitalization for acute myocardial infarction,
      angina, or ischemic heart disease, and who had been dispensed cardiovascular
      medicines in the 3 months posthospitalization. The main outcome measures were
      duration of first treatment episode, duration of overall treatment episode, and
      adherence with recommended therapies: angiotensin-converting enzyme (ACE)
      inhibitors, angiotensin II receptor blockers (ARBs), lipid-lowering therapy,
      calcium channel blockers (CCBs), beta-blockers, and antiplatelet therapy.
      RESULTS: The median duration of overall treatment was 6.2 years [95% confidence
      interval (CI): 6.0-6.4] for lipid-lowering therapy, 5.4 years (95% CI: 5.1-5.5)
      for ACE inhibitors/ARBs, 5.0 years (95% CI: 4.8-5.1) for antiplatelets, 3.4 years
      (95% CI: 3.3-3.6) for beta-blockers, and 2.8 years (95% CI: 2.6-3.0) for CCBs.
      Adherence was 72% for CCBs, 75% for ACE inhibitors/ARBs, 84% for lipid-lowering
      therapy, and 84% for antiplatelets other than aspirin. The median time without
      therapy was 4.5 months or less for ACE inhibitors/ARBs, antiplatelets, and lipid
      lowering therapy. CONCLUSION: Problems with medication adherence can relate to
      either persistence or compliance during treatment. This novel method provides a
      way to determine which of these factors is most problematic when considering
      chronic therapies. We found that Australian veterans with established
      cardiovascular disease are persistent with their cardiovascular therapy, with
      only small gaps in therapy.

PMID- 19587602
TI  - Perception of cardiovascular risk and comparison with actual cardiovascular risk.
AB  - BACKGROUND: Current guidelines recommend treating patients according to their
      absolute cardiovascular disease (CVD) risk. We examined perception of CVD risk
      among adults and how it can be compared with actual CVD risk. METHODS: The
      perception of CVD risk was assessed by two questions asking about participants'
      'risk to get a heart attack or a stroke over the next 10 years' using
      semiquantitative and quantitative answers in a population-based survey of 816
      individuals aged 40-64 years in the Seychelles (African region). Actual CVD risk
      was calculated using a standard risk prediction score and 24% of adults aged 40
      64 years had elevated risk. RESULTS: Only 59% of individuals could give an
      estimate of perceived CVD risk based on the semiquantitative question and 31%
      based on the quantitative question. Reporting a perceived CVD risk was strongly
      associated with high socio-economic status (SES; odds ratio = 9). Among
      individuals who reported a perceived CVD risk, 48% overestimated their perceived
      risk versus their actual risk. Reporting a high perceived CVD risk was associated
      with treatment for CVD risk factors, older age, low SES, and overweight.
      Reporting a low perceived CVD risk was associated with male sex, younger age,
      education, normal BMI, and leisure time exercise. CONCLUSION: Only half of the
      individuals could provide an estimate of their perceived CVD risk, and this
      perception was strongly associated with SES. Individuals under treatment
      perceived higher CVD risk than nontreated individuals. Further studies should
      determine how risk-related information can be better conveyed to individuals as a
      means to improve adherence to healthy lifestyles and/or treatment.

PMID- 19587603
TI  - Habitual physical activity is associated with endothelial function and
      endothelial progenitor cells in patients with stable coronary artery disease.
AB  - BACKGROUND: Exercise training reduces mortality in patients with coronary artery
      disease (CAD); however, the impact of habitual physical activity level (PAL) on
      vascular endothelial function and circulating endothelial progenitor cells (EPCs)
      remain unknown. METHODS: We assessed habitual PAL using a validated International
      Physical Activity Questionnaire in 116 patients (67.8+/-9.5 years; 81% male) with
      stable CAD and preserved left ventricular ejection fraction > or =45%. The number
      of circulating CD34/KDR+ and CD133/KDR+ EPCs was determined by flow cytometry,
      and brachial artery flow-mediated dilation (FMD) was measured. RESULTS: The mean
      PAL of CAD patients with 1644 MET min/week (where MET is metabolic equivalents).
      With higher habitual PAL tertiles, there were significant linear trends of
      increased FMD (P = 0.001) and CD133/KDR+ EPCs (P = 0.03), but not of CD34/KDR+
      EPCs. Patients with the highest tertile of PAL were associated with an absolute
      increase of 1.89% in FMD (relative increase 68%, P = 0.003) and 0.12% in
      CD133/KDR+ EPCs (relative increase 44%, P = 0.01) compared with those in the
      lowest tertile of PAL, after adjusting for age, sex, presence of hypertension,
      diabetes mellitus, hypercholesterolemia, smoking, and the use of medications
      including statins. However, neither CD34/KDR+ nor CD133/KDR+ EPCs significantly
      correlated with FMD. CONCLUSION: This study showed that higher habitual PAL in
      patients with CAD was associated with higher FMD and EPC count. Nonetheless, FMD
      only significantly correlated with increased PAL, but not EPC, suggesting that
      increased physical activity improves endothelial function through mechanisms
      other than increasing EPC count.

PMID- 19587604
TI  - Sudden death in persons younger than 40 years of age: incidence and causes.
AB  - BACKGROUND: The problem of sudden death in the young is currently debated and
      measures for prevention are being evaluated worldwide. Information on the
      incidence and causes of sudden (cardiac) death in the young (1-40 years) is
      essential for the development of these preventive strategies. METHODS: Incidence
      estimates and causes of death were determined using death certificate data of out
      of-hospital sudden deaths recorded by Statistics Netherlands from 1996 to 2006.
      To define sudden death, International Classification of Diseases codes were
      selected based on a systematic review of the literature assessing the most common
      causes of sudden death in the young. RESULTS: The incidence of sudden death was
      2.07 (2.06-2.07 per 100 000 person-years). The incidence was higher for men (2.86
      per 100 000 person-years) than for women (1.24 per 100 000 person-years) and
      increased by age. The majority of sudden deaths was of cardiac origin. Sudden
      cardiac death incidence was 1.62 (1.61-1.62 per 100 000 person-years). In 9% the
      cause of death remained unexplained. CONCLUSION: The incidence of sudden death in
      the young is 2.07 per 100 000 person-years. Treatable cardiac causes (such as
      coronary atherosclerosis and inherited cardiac diseases) are often underlying for
      the sudden death. This information is helpful in the development of preventive
      strategies.

PMID- 19587605
TI  - The dicrotic notch as alternative time-reference point to measure local pulse
      wave velocity in the carotid artery by means of ultrasonography.
AB  - OBJECTIVES: Increased arterial stiffness is associated with cardiovascular
      disease. Its applicability in individual patient management, however, is limited
      due to lack of reliable methods. We developed a method to measure arterial
      stiffness by means of local pulse wave velocity (PWV), using multiple M-mode
      ultrasound and the dicrotic notch (PWVdn) rather than the systolic foot (PWVsf)
      as time-reference point. METHODS: Systolic foot and dicrotic notch were
      determined in 14 simultaneously recorded distension waveforms obtained in young
      and older participants (mean age 26 and 59 years). Linear regression was
      performed on echo-line position and time-reference point, resulting in a local
      PWV estimate, either PWVsf or PWVdn. RESULTS: PWVdn, at about mean arterial
      pressure, had a better intra-individual variability (0.6 m/s) than PWVsf (1.1
      m/s). The expected difference in stiffness between the two age categories was
      identified by PWVdn (P < 0.0001), but not by PWVsf. Moreover, in contrast to
      PWVsf, PWVdn showed a significant correlation with relative distension (r = 0.56)
      and the local distensibility coefficient (r = 0.52). CONCLUSION: PWVdn is a
      noninvasive and suitable measure of arterial stiffness: it has a good
      reproducibility, discriminates well between age groups, and correlates with local
      distensibility. PWVdn does not require additional assessment of distance or local
      pulse pressure. Furthermore, PWVdn is measured locally, at near-mean arterial
      pressure, thereby better reflecting the effective arterial stiffness, which
      determines the load the left ventricle is subjected to as it ejects blood.

PMID- 19587606
TI  - The role of conventional and novel mechanisms in explaining increased risk of
      cardiovascular events in offspring with positive parental history.
AB  - BACKGROUND: Parental history is a widely accepted risk factor for offspring
      cardiovascular events, although the mechanisms remain unclear. We examined the
      contribution of conventional and novel risk factors in explaining the excess risk
      of cardiovascular events in offspring with positive parental history (PH+).
      METHODS AND RESULTS: We collected conventional (blood pressure, cholesterol,
      adiposity), lifestyle, and novel (C-reactive protein, CRP) risk factors at
      baseline in participants from the Scottish Health Surveys (n = 5946, 44.5% men,
      aged 53.6 +/- 12.4 years), who were followed up over an average of 7.1 years for
      cardiovascular disease (CVD) events (a composite of fatal and nonfatal events
      incorporating acute myocardial infarction, coronary artery bypass surgery,
      percutaneous coronary angioplasty, stroke, heart failure). Younger PH+
      participants (<65 years) were at higher risk of incident CVD events [age-adjusted
      and sex-adjusted hazard ratio = 1.91, 95% confidence interval (CI) 1.21-3.00]
      compared with PH-. Despite an association of PH+ with blood pressure, total and
      high-density lipoprotein cholesterol, CRP, and physical activity, less than 15%
      of the excess risk was explained through conventional and novel risk factors.
      However, the greatest risk of CVD was observed in PH+ participants with elevated
      CRP (> or =3 mg/l) (hazard ratio = 2.99, 95% CI 2.15-4.16) or hypertension
      (hazard ratio = 2.87, 95% CI 2.07-3.99). CONCLUSION: Only a small amount of the
      excess CVD risk associated with PH+ is accounted for by conventional and novel
      mechanisms. However, the combination of elevated CRP or hypertension with PH+
      substantially increases the risk of CVD.

PMID- 19587607
TI  - Evaluation of the awareness, control and cost-effectiveness of hypertension
      treatment in a Brazilian city: populational study.
AB  - OBJECTIVES: Hypertension is a highly prevalent disease worldwide, constituting
      one of the main risk factors for cardiovascular morbidity and mortality. The aims
      of this study were to evaluate the level of awareness and control of hypertension
      comparing sex, socioeconomic and educational level, BMI and drug therapy in over
      40-year-old patients. The cost-effectiveness of the main pharmacologic classes of
      antihypertensives, as monotherapy and combination therapy, was also assessed.
      METHODS: In this randomized and cross-sectional populational study, a sample of
      738 hypertensive adults with ages at least 40 years were evaluated. Of these, 345
      (46.7%) were men and 393 (53.3%) were women. RESULTS: A total of 72.9% of the
      hypertensives knew about their disease. Women in the 40-49 and 50-59 age groups
      and obese individuals had a higher rate of awareness of their hypertensive
      status. The rates of awareness were similar in different social classes and
      educational levels, however, blood pressure control varied. beta-Blockers were
      the most effective drugs to control blood pressure with no differences being
      observed between monotherapy and combinations. Diuretics were the most cost
      effective. CONCLUSION: Approximately half of the participants received
      monotherapy. The best percentage of control with monotherapy was obtained with
      beta-blockers but the diuretics treatment was the most cost-effective. The levels
      of awareness and control were high compared with developed countries, most
      evident in the higher social classes and higher education levels.

PMID- 19587608
TI  - Ankle-brachial index is lower in hypertensive than in normotensive individuals in
      a cardiovascular risk population.
AB  - BACKGROUND: Hypertension is an established risk factor for peripheral arterial
      disease (PAD), but the prevalence of this condition in hypertensive patients
      without comorbidities is unknown. METHODS: In this study, we assess the
      prevalence and factors associated with PAD, and the usefulness of ankle-brachial
      index (ABI) in evaluating cardiovascular risk in hypertensive patients without
      cardiovascular or renal disease or previously known diabetes mellitus. We
      measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed
      glucose disorders, metabolic syndrome, obesity or a 10-year risk of
      cardiovascular disease death of 5% or more according to the Systematic Coronary
      Risk Evaluation System. RESULTS: The prevalence of PAD (defined as ABI < or
      =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was
      7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model,
      hypertension remained an independent factor associated with PAD (adjusted odds
      ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between
      PAD and metabolic risk factors. SBP and pulse pressure increased linearly across
      subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P <
      0.001). CONCLUSION: Subclinical PAD is common in hypertensive patients even
      without comorbidities. The measurement of ABI is an efficient method to identify
      patients with increased cardiovascular risk and worth performing to hypertensive
      patients, particularly those with pulse pressure above 65 mmHg. Uniform
      criterions of defining PAD and borderline PAD would aid physicians in clinical
      decision-making.

PMID- 19587609
TI  - Effect of vitamin D on blood pressure: a systematic review and meta-analysis.
AB  - OBJECTIVES: Vitamin D insufficiency has been linked to hypertension and
      cardiovascular events in observational studies. It is unclear whether vitamin D
      supplementation can reduce blood pressure, and, if so, by how much. METHODS: We
      performed a systematic review and meta-analysis to examine whether vitamin D
      reduces blood pressure. Databases including MEDLINE, EMBASE, the Cumulative Index
      to Nursing and Allied Health Literature and the Cochrane library were searched,
      supplemented by searches of grey literature, unpublished trials and references
      from included studies. Studies were assessed by two reviewers independently
      according to a prespecified protocol. Interventions included activated vitamin D,
      unactivated vitamin D2 and D3 and ultraviolet B radiation. RESULTS: Eleven
      randomized, controlled trials fulfilled the inclusion criteria. Studies were
      small and of variable methodological quality. Mean baseline blood pressure was
      more than 140/90 mmHg in eight studies. Meta-analysis of these eight studies
      showed a nonsignificant reduction in systolic blood pressure in the vitamin D
      group compared with placebo [-3.6 mmHg, 95% confidence interval (CI) -8.0 to
      0.7]. A small, statistically significant reduction was seen in diastolic blood
      pressure (-3.1 mmHg, 95% CI -5.5 to -0.6). Subgroup analysis suggested that
      unactivated vitamin D produced a greater fall in systolic blood pressure than
      activated vitamin D (-6.2 mmHg, 95% CI -12.32 to -0.04, vs. +0.7 mmHg, 95% CI 
      4.8 to 6.2). No reduction in blood pressure was seen in studies examining
      patients who were normotensive at baseline. CONCLUSION: We found weak evidence to
      support a small effect of vitamin D on blood pressure in studies of hypertensive
      patients.

PMID- 19587610
TI  - Control of systemic and pulmonary blood pressure by nitric oxide formed through
      neuronal nitric oxide synthase.
AB  - Nitric oxide formed by neuronal nitric oxide synthase (nNOS) in the brain,
      autonomic inhibitory (nitrergic) nerves, and heart plays important roles in the
      control of blood pressure. Activation of nitrergic nerves innervating the
      systemic vasculature elicits vasodilatation, decreases peripheral resistance, and
      lowers blood pressure. Impairment of nitrergic nerve function, as well as
      endothelial dysfunction, results in systemic and pulmonary hypertension and
      decreased regional blood flow. Blockade of nNOS activity in the brain,
      particularly the medulla and hypothalamus, causes systemic hypertension. Under
      hypertensive states, such as those in spontaneously hypertensive and Dahl salt
      sensitive rats, the expression of the nNOS gene in the brain is increased; this
      appears to counteract the activated sympathetic function in the vasomotor center.
      The present article summarizes information concerning the modulation of systemic
      and pulmonary hypertension through nNOS-derived nitric oxide produced in the
      brain and periphery.

PMID- 19587611
TI  - Accuracy of endometrial thickness in detecting benign endometrial pathology in
      postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to determine whether an endometrial
      thickness less than 5 mm on transvaginal ultrasound (TVUS) is sufficient to
      exclude benign endometrial lesions in postmenopausal women with bleeding and to
      determine a cutoff value below which benign endometrial pathology could be ruled
      out. METHODS: Electronic medical records of consecutive postmenopausal women
      presenting with vaginal bleeding suspicious for benign pathology were reviewed
      between September 2002 and December 2007. All women underwent TVUS with
      endometrial stripe measurement followed by saline infusion sonography (SIS).
      Accuracy of endometrial echo thickness for detecting intracavitary masses was
      compared with the reference standard of SIS. A receiver operating characteristic
      curve was constructed to calculate whether other cutoff values would be more
      accurate than 5 mm in detecting benign endometrial masses. RESULTS: A total of
      1,097 women were referred during the study period; 135 met the inclusion criteria
      and underwent TVUS followed by SIS. The endometrial echo was less than 5 mm in
      43% and 5 mm or greater in 57%. The overall prevalence of polyps or fibroids was
      50%. Using an endometrial echo cutoff less than 5 mm, sensitivity was 76% (95%
      CI, 65-85), specificity was 63% (95% CI, 51-73), positive predictive value was
      67%, and negative predictive value was 72%. The area under the receiver operating
      characteristic curve for detection of benign masses was 0.79 (95% CI, 0.72-0.87).
      We were unable to determine a cutoff value below which benign endometrial
      pathology could be excluded. CONCLUSIONS: With an endometrial thickness cutoff of
      5 mm a considerable amount of benign endometrial pathology in postmenopausal
      women with bleeding is missed, and SIS or hysteroscopy may be warranted.

PMID- 19587612
TI  - Some molecular effectors of antidepressant action of quetiapine revealed by DNA
      microarray in the frontal cortex of anhedonic rats.
AB  - OBJECTIVES AND METHODS: We have previously demonstrated that quetiapine (QTP) had
      antidepressant-like action by using the chronic mild stress (CMS) paradigm, an
      animal model of human depression. The aim of this study was to investigate the
      molecular mechanism(s) of QTP antidepressant effect by coupling the CMS protocol
      with Affymetrix microarray technology to screen the entire rat genome for gene
      changes in the frontal cortex. RESULTS: The genes regulated by the administration
      of CMS whose transcription was reversed by chronic QTP treatment (2 mg/kg/day)
      were 42 (23 upregulated and 19 downregulated). The transcripts that showed no
      significant altered expression levels in anhedonic rats but were regulated by the
      administration of QTP were 19 (nine upregulated and 10 downregulated). On the
      whole, the action of QTP prevented the stress-induced impairment of some
      processes involved in central nervous system development or having a crucial role
      for viability of neural cells and cell-cell communications, like regulation of
      signal transduction, inorganic cation transport, membrane organization, and
      neurite morphogenesis. For 11 genes (Ptgs2, Gad1, Plcb1, Camk2a, Homer1, Senp2,
      Junb, Nfib, Hes5, Capon, and Marcks), significant differential expressions were
      confirmed by real-time reverse-transcriptase polymerase chain reaction.
      CONCLUSION: We have shown that chronic QTP treatment prevented anhedonia and
      reversed, at least in part, the changes of gene expression induced by CMS in the
      rat frontal cortex. We have also identified and confirmed by two different
      methods that 11 genes, representing molecular targets of QTP, are presumably the
      effectors of its clinical efficacy.

PMID- 19587613
TI  - Sacroiliac joint radiofrequency denervation: who benefits?

PMID- 19587614
TI  - Spinal procaine is less neurotoxic than mepivacaine, prilocaine and bupivacaine
      in rats.
AB  - BACKGROUND AND OBJECTIVES: Lidocaine has been reported to be more neurotoxic than
      other local anesthetics. Alternatives to lidocaine with lower toxicity and
      shorter duration of action are desirable. Therefore, we compared the histologic
      and functional changes induced by intrathecal injection of prilocaine,
      mepivacaine, procaine, and bupivacaine in rats. METHODS: Rats (n = 184) randomly
      received via an intrathecal catheter 0.12 microL/g body weight of 2%, 10%, 16%,
      or 20% prilocaine, mepivacaine, or procaine; 0%, 0.5%, 2.5%, 4%, or 5%
      bupivacaine in distilled water; or distilled water or 15% glucose solution alone
      as a control. We evaluated neurofunction by analyzing walking behavior and
      sensory threshold and examined the L3 spinal cord, posterior and anterior roots,
      and cauda equina by light and electron microscopy. RESULTS: The recovery time to
      normal ambulation after intrathecal injection was significantly faster with
      procaine than with the other 3 drugs at all concentrations. There were no
      significant differences in the sensory threshold among the 4 anesthetics.
      Histologic damage was observed only in rats treated with greater than 16%
      prilocaine or mepivacaine or with greater than 4% bupivacaine. Histologic damage
      occurred at the posterior root and posterior white matter and was characterized
      by axonal degeneration. Rats treated with procaine, even at 20%, showed no
      histologic abnormalities. CONCLUSION: In this animal model, the neurotoxicity of
      intrathecal procaine was the mildest, and the recovery time to ambulation with
      procaine was the fastest among the 4 tested anesthetics.

PMID- 19587615
TI  - Bicarbonate plus epinephrine shortens the onset and prolongs the duration of
      sciatic block using chloroprocaine followed by bupivacaine in sprague-dawley
      rats.
AB  - BACKGROUND: Chloroprocaine is a fast-acting local anesthetic, whereas bupivacaine
      is a long-acting one. They have been coadministered with limited success. The
      objective of this study was to determine the effect of additives on the efficacy
      of regional blockade using chloroprocaine followed by bupivacaine. METHODS: Four
      groups of Sprague-Dawley rats, 20 each, were administered chloroprocaine followed
      by bupivacaine to induce sciatic nerve blockade. Group 1 received chloroprocaine
      with isotonic sodium chloride solution followed by bupivacaine and was used as a
      control. Group 2 received chloroprocaine with isotonic sodium chloride solution
      and epinephrine followed by bupivacaine with epinephrine. Group 3 received
      chloroprocaine with sodium bicarbonate followed by bupivacaine, and group 4
      received chloroprocaine with sodium bicarbonate and epinephrine followed by
      bupivacaine with epinephrine. The time to onset and duration of anesthesia were
      measured for all 4 groups. RESULTS: The block using chloroprocaine followed by
      bupivacaine in group 1 had an onset of 2.5 mins (SD, 0.4 mins) and duration of
      104 mins (SD, 16 mins). Adding epinephrine to both chloroprocaine and bupivacaine
      (group 2) did not significantly change the onset (2.8 mins [SD, 1.3 mins]; P =
      0.35) or duration (110 mins [SD, 25 mins]; P = 0.23). With group 3, adding
      bicarbonate to chloroprocaine hastened the onset (1.2 mins [SD, 0.4 mins]; P <
      0.0001) and shortened the duration (87 mins [SD, 13 mins]; P = 0.008). In group
      4, adding bicarbonate and epinephrine to chloroprocaine and epinephrine to
      bupivacaine hastened the onset (1.4 mins [SD, 0.4 mins]; P < 0.0001) and
      increased the duration (130 mins [SD, 23 mins]; P < 0.0001). CONCLUSIONS: Sodium
      bicarbonate plus epinephrine shortens the onset and prolongs the duration of a
      chloroprocaine-bupivacaine sciatic block in Sprague-Dawley rats.

PMID- 19587616
TI  - Structural injury to the human sciatic nerve after intraneural needle insertion.
AB  - BACKGROUND: Recent clinical reports suggest that intraneural needle placement may
      not always lead to neurologic injury. To explain the absence of neurologic
      complications in these reports, we studied the risk and extent of nerve injury
      after intentional needle-nerve placement in a cryopreserved human sciatic nerve.
      METHODS: The sciatic nerve was dissected from a cryopreserved cadaver through
      partial exposure. Needles were inserted through the nerve, using blunt-tip (30
      degrees beveled) (group A) and sharp-tip (15 degrees beveled) (group D) needles.
      Five needle insertions were made for each needle type. Subsequently, transverse
      nerve sections at 10 needle trajectories were processed. Nerve samples were
      stained with hematoxylin-eosin, Masson trichromic, and immunohistochemical
      stains. In each section, the following variables were quantified: total number of
      fascicles and vessels in the immediate vicinity of the needle trajectories and
      the number of injured fascicles and vessels. RESULTS: A total of 520 fascicles
      were quantified, of which 134 were in contact with the needle trajectories. The
      numbers of fascicles and vessels per section were 65 +/- 8 and 14 +/- 7,
      respectively. A mean of 16 +/- 5 fascicles were found in contact with the needle
      trajectory (group A: 17+/- 3, group D: 15 +/- 6). Of these, 4 fascicles (3.2%)
      and 1 intraneural vessel were found damaged in group D. No fascicular or vascular
      injuries were found in group A. CONCLUSIONS: Our findings suggest that
      intraneural needle insertion may more commonly result in interfascicular rather
      than intrafascicular needle placement.

PMID- 19587617
TI  - Outcome predictors for sacroiliac joint (lateral branch) radiofrequency
      denervation.
AB  - BACKGROUND AND OBJECTIVE: Sacroiliac (SI) joint pain is a challenging condition
      characterized by limited treatment options. Recently, numerous studies have
      reported excellent intermediate-term outcomes after lateral-branch radiofrequency
      (RF) denervation, but these studies are characterized by wide variability in
      technique, selection criteria, and patient characteristics. The purpose of this
      study was to determine whether any demographic or clinical variables can be used
      to predict SI joint RF denervation outcome. METHODS: Seventy-seven patients with
      refractory, injection-confirmed SI joint pain underwent SI joint denervation at 2
      academic institutions. A composite binary variable "successful" outcome was
      predefined as greater than 50% reduction in pain lasting at least 6 months
      coupled with a positive global perceived effect. Secondary outcome measures
      included Oswestry Disability Index scores, medication reduction, and retention on
      active duty for soldiers. Factors retrospectively evaluated for their association
      with outcome included demographic variables, duration of pain, opioid usage, pain
      referral pattern, physical examination signs, number of blocks and percentage of
      pain relief after SI joint injection, prognostic lateral-branch blocks, previous
      surgery, levels lesioned, RF technique, disability status, and coexisting medical
      conditions. RESULTS: Forty patients (52%) obtained a positive outcome. In
      multivariate analysis, preprocedure pain intensity, age older than 65 years, and
      pain radiating below the knee were significant predictors of failure. A trend was
      noted whereby patients receiving regular opioid therapy were more likely to
      experience a negative outcome. The use of cooled, rather than conventional RF,
      was associated with a higher percentage of positive outcomes. CONCLUSIONS:
      Whereas several factors were found to influence outcome, no single clinical
      variable reliably predicted treatment results. The use of more stringent
      selection criteria was not associated with better outcomes.

PMID- 19587618
TI  - Minimum effective volume of local anesthetic for ultrasound-guided
      supraclavicular brachial plexus block.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the minimum
      effective anesthetic volume required to produce an effective supraclavicular
      block for surgical anesthesia using an ultrasound (US)-guided technique. METHODS:
      Twenty-one adults undergoing elective upper limb surgery received a US-guided
      supraclavicular block. The initial volume of local anesthetic (LA; 50:50 mixture
      of lidocaine 2% and bupivacaine 0.5% with epinephrine) injected was 30 mL, which
      was subsequently varied by 5 mL for each consecutive patient according to the
      response of the previous patient. The minimum effective anesthetic volume in 50%
      of patients was determined using the Dixon and Massey up-and-down method. The
      effective volume in 95% of patients (ED95) was calculated using probit
      transformation and logistic regression. RESULTS: The minimum effective anesthetic
      volume in 50% and calculated effective volume in 95% of patients were 23 mL (95%
      confidence interval, 13-39 mL) and 42 mL (95% confidence interval, 19-65 mL),
      respectively. Seven patients received supplemental LA, with no patient requiring
      a general anesthetic. CONCLUSION: In this study, the minimum volume required for
      US-guided supraclavicular block in 50% of patients was 23 mL, and in 95% of
      patients was 42 mL. Under the present study conditions, the calculated volume of
      LA required for US-guided supraclavicular block does not seem to differ from the
      conventionally recommended volume required for supraclavicular blocks using non
      US-based nerve localization techniques.

PMID- 19587619
TI  - Survey of the utilization of regional and general anesthesia in a tertiary
      teaching hospital.
AB  - BACKGROUND: Although the subspecialty of regional anesthesiology has become an
      important focus during residency training, there are many factors that might
      influence a resident's experience in regional anesthesia (RA). There are few data
      examining the utilization of regional techniques in an anesthesiology residency
      program. We undertook a prospective observational study to determine the
      frequency and reasons for not choosing RA in cases for which it was considered an
      option. METHODS: All scheduled operative procedures that were amenable to
      neuraxial or major peripheral regional anesthetic techniques were surveyed. Data
      recorded included the type of intraoperative anesthetic used, type of
      anesthesiology faculty performing the regional block (regional anesthesiologist
      vs general anesthesiologist), and reasons for not choosing RA when a regional
      anesthetic technique was feasible. RESULTS: Of the 2301 surgical procedures
      amenable to a regional technique, 839 (36.5%) involved use of regional
      anesthetic, and 1462 (63.5%) involved only a general anesthetic. Of the subjects
      receiving RA, 32% were performed by general anesthesiology faculty, and 68% were
      performed by regional anesthesiology faculty. The most common type of regional
      anesthetic performed by the general anesthesiology faculty was neuraxial blockade
      (95.2%) (vs 52.5% by regional anesthesiology faculty). Of the cases not involving
      RA, the reasons were anesthesiology related (40%), surgeon related (34%), patient
      related (12%), and medical contraindication related (14%). CONCLUSIONS: Our
      prospective observational study suggests that anesthesiology-related reasons may
      be an important factor for not undertaking these techniques. Although we did not
      specifically examine the effect on resident education, our study does provide
      some evidence to support program directors and department chiefs to set up their
      regional rotations with faculty most likely to perform RA.

PMID- 19587620
TI  - Clinical impact of epidural anesthesia simulation on short- and long-term
      learning curve: High- versus low-fidelity model training.
AB  - BACKGROUND AND OBJECTIVES: Epidural anesthesia is a technically challenging
      regional anesthetic technique that can be difficult to teach to novices. Epidural
      simulators are now available to allow realistic training within a safe and
      controlled environment before attempting the procedure on patients. Potentially,
      this may improve skill acquisition by novice residents. The purpose of this study
      was to examine the effect of a high-fidelity epidural anesthesia simulator on
      residents' ability to perform their first labor epidurals and on their learning
      curve compared with a group having training with a low-fidelity model. METHODS:
      Second-year anesthesia residents were recruited. Subjects were randomized into 2
      groups and practiced epidural needle insertion on a high-fidelity epidural
      simulator or on a low-fidelity model. Subjects were then repeatedly videotaped
      performing epidural anesthesia over a 6-month period. Two blinded examiners
      graded each session, using a previously validated Global Rating Scale and Manual
      Skill Checklist to judge the skill level. RESULTS: Seventy-two sessions performed
      by 24 residents were recorded. Manual Skill Checklist and Global Rating Scale
      total scores were compared across the 2 study groups at baseline (first
      epidural), middle (31-90 epidurals) and late (>90 epidurals) time points using
      independent-samples t tests. No significant differences in scores were detected
      at either one of these time points. CONCLUSION: Our study shows that a simple
      model can be as useful for learning how to place an epidural catheter as an
      expensive anatomically correct simulator. New and more technologically advanced
      simulators should be compared against lower fidelity models to establish their
      utility and cost-effectiveness.

PMID- 19587622
TI  - Vertical infraclavicular brachial plexus block: needle redirection after
      elicitation of elbow flexion.
AB  - BACKGROUND: In vertical infraclavicular brachial plexus block, success depends on
      distal flexion or extension response. Initially, elbow flexion (lateral cord) is
      generally observed. However, specific knowledge about how to reach the medial or
      posterior cord is lacking. We investigated the mid-infraclavicular area in
      undisturbed anatomy and tested the findings in a clinical setting. METHODS: Along
      a length of 35 mm around the mid-infraclavicular point, cryomicrotomy sections of
      5 shoulders from cadavers were used to determine the topography of the cords in
      relation to one another and the axillary artery. Based on the findings, the
      anesthesiologists were instructed on how to elicit a distal motor response after
      an initial elbow flexion response in single-shot, Doppler-aided, vertical
      infraclavicular block in a series of 50 consecutive patients. RESULTS: In the mid
      infraclavicular area, the lateral cord always lies anterior to either the
      posterior or the medial cord and cranial to the axillary artery; the posterior
      cord was always cranial to the medial cord; and both cords were always located
      dorsal to the artery. In the clinical study, in 98% of the included patients,
      finger flexion or finger and/or wrist extension was elicited as predicted. The
      overall success rate was 92%. No vascular or lung puncture occurred. CONCLUSIONS:
      In the clinical study, in 98% of cases, the final stimulation response of
      posterior or medial cord was found as predicted by the findings of the anatomic
      study. Once elbow flexion is elicited, a further (ie, deeper) advancement of the
      needle will result in the proper distal motor response.

PMID- 19587621
TI  - Implications of a permanent cardiac pacemaker in peripheral nerve blockade.
AB  - Patients with permanent cardiac pacemakers (PPMs) are vulnerable to
      electromagnetic interference from electrical equipment used in the operating room
      environment. Electromagnetic interference may lead to PPM malfunction with
      potential harmful effects to the patient. Conventional techniques for peripheral
      nerve blockade include the use of electrical nerve stimulation (NS) for nerve
      localization. The hazards of NS, especially when applied near the implanted PPM
      sites, are not known. In the absence of available guidelines regarding the safe
      use of NS in the setting of an implanted PPM, we recommend a combined guidance
      approach for peripheral nerve blockade using ultrasound for nerve localization
      along with low-current NS for nerve identification.

PMID- 19587623
TI  - Minimal local anesthetic volume for peripheral nerve block: a new ultrasound
      guided, nerve dimension-based method.
AB  - BACKGROUND AND OBJECTIVES: Nerve blocks using local anesthetics are widely used.
      High volumes are usually injected, which may predispose patients to associated
      adverse events. Introduction of ultrasound guidance facilitates the reduction of
      volume, but the minimal effective volume is unknown. In this study, we estimated
      the 50% effective dose (ED50) and 95% effective dose (ED95) volume of 1%
      mepivacaine relative to the cross-sectional area of the nerve for an adequate
      sensory block. METHODS: To reduce the number of healthy volunteers, we used a
      volume reduction protocol using the up-and-down procedure according to the Dixon
      average method. The ulnar nerve was scanned at the proximal forearm, and the
      cross-sectional area was measured by ultrasound. In the first volunteer, a volume
      of 0.4 mL/mm of nerve cross-sectional area was injected under ultrasound guidance
      in close proximity to and around the nerve using a multiple injection technique.
      The volume in the next volunteer was reduced by 0.04 mL/mm in case of complete
      blockade and augmented by the same amount in case of incomplete sensory blockade
      within 20 mins. After 3 up-and-down cycles, ED50 and ED95 were estimated.
      Volunteers and physicians performing the block were blinded to the volume used.
      RESULTS: A total 17 of volunteers were investigated. The ED50 volume was 0.08
      mL/mm (SD, 0.01 mL/mm), and the ED95 volume was 0.11 mL/mm (SD, 0.03 mL/mm). The
      mean cross-sectional area of the nerves was 6.2 mm (1.0 mm). CONCLUSIONS: Based
      on the ultrasound measured cross-sectional area and using ultrasound guidance, a
      mean volume of 0.7 mL represents the ED95 dose of 1% mepivacaine to block the
      ulnar nerve at the proximal forearm.

PMID- 19587624
TI  - The rectus sheath block: accuracy of local anesthetic placement by trainee
      anesthesiologists using loss of resistance or ultrasound guidance.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the accuracy of
      local anesthetic placement in the rectus sheath block when performed by trainee
      anesthetists using loss of resistance (LOR) or ultrasound guidance. METHODS:
      Eighty-one patients undergoing laparoscopic surgery were randomly assigned to
      undergo rectus sheath block by either LOR or ultrasound guidance. Trainee
      anesthesiologists were also randomly assigned to provide the rectus sheath block
      by LOR or by using ultrasound. The placement of local anesthetic was recorded
      using ultrasound. RESULTS: The placement of local anesthetic by LOR was accurate
      in 45% of attempts but was superficial and deep to the rectus sheath in 34% and
      21% of punctures, respectively. Accurate placement of local anesthetic within the
      rectus sheath decreased significantly as body mass index increased. Ultrasound
      guidance significantly improved the accuracy of needle placement, with 89% of
      abdominal punctures being correctly placed at the time of first injection of
      local anesthetic. An additional fascial plane lying at variable distance above
      the anterior layer of the rectus sheath was commonly observed. CONCLUSIONS:
      Ultrasound guidance improves the accuracy of local anesthetic placement when
      undertaking the rectus sheath block. An additional fascial plane above the
      anterior layer of the rectus sheath may be wrongly perceived as the anterior
      layer of the rectus sheath when the block is undertaken without the aid of
      ultrasound.

PMID- 19587625
TI  - Adverse outcomes associated with stimulator-based peripheral nerve blocks with
      versus without ultrasound visualization.
AB  - BACKGROUND AND OBJECTIVES: In this retrospective study, we queried our Quality
      Improvement database of anesthetic-related complications to evaluate the
      frequency of noncatheter peripheral nerve block-related adverse occurrences. We
      hypothesized that adverse complications of nerve blockade are less common when
      ultrasonography is used in conjunction with peripheral nerve stimulation to guide
      needle placement, when compared with the sole use of physical landmarks and nerve
      stimulation. METHODS: We queried our departmental Quality Improvement electronic
      database for adverse outcomes associated with peripheral nerve blocks. Billing
      records were used to provide the denominator of the total number of blocks using
      both techniques of neurolocation. The types of blocks considered in this analysis
      were interscalene, axillary, femoral, sciatic, and popliteal sciatic blocks. The
      total numbers of complications of nerve blockade with each type of guidance were
      then compared, as were specific subsets of adverse effects. RESULTS: There were
      5436 consecutive peripheral noncatheter block cases (interscalene, axillary,
      femoral, sciatic, popliteal) during the 28-month period surveyed, with 3290
      guided by landmark-nerve stimulation, and 2146 by ultrasound-nerve stimulation.
      Eight adverse outcomes occurred among patients having blocks guided by landmark
      nerve stimulation technique, including 5 seizures and 3 nerve injuries. There
      were no such occurrences in the ultrasound-nerve stimulation group. When
      comparing the 4 brachial plexus block-related seizures that occurred with
      landmark guidance versus none with ultrasound guidance, the associated risk of
      seizures reached statistical significance (P = 0.044 by Fisher exact test). There
      was no difference between the 2 groups in the number of seizures occurring with
      lower extremity blocks, or in the frequency of neurologic injury. CONCLUSIONS:
      High-definition ultrasonography offers potential advantages in the administration
      of peripheral nerve blockade. The significant difference in major central nervous
      system local anesthetic toxicity observed in this study supports the use of
      ultrasound guidance in conjunction with peripheral nerve stimulation to provide
      brachial plexus peripheral nerve blockade in an academic, ambulatory anesthesia
      practice.

PMID- 19587627
TI  - Ultrasound-guided obturator nerve block: an interfascial injection approach
      without nerve stimulation.
AB  - BACKGROUND AND OBJECTIVES: For knee surgery, obturator nerve block (ONB) has been
      shown to enhance postoperative analgesia provided by femoral block. Current
      techniques for obturator block use surface landmarks or ultrasound guidance (USG)
      with nerve stimulation. This preliminary observational study evaluated the
      success of an ultrasound-guided ONB without the additional use of nerve
      stimulation. METHODS: Thirty patients scheduled for knee surgery under general
      anesthesia with nerve block for postoperative analgesia had ONB performed using
      USG and injection of 10 mL 0.5% ropivacaine with epinephrine. Half of the
      ropivacaine was injected between the pectineus and adductor brevis muscles, and
      half between the adductor brevis and adductor magnus muscles. The strength of
      thigh adduction was measured at 5, 10, and 15 mins after injection, and 50%
      strength reduction at 15 mins indicated a successful block. RESULTS: All patients
      showed reduction of strength, and 28 of 30 or 93% met the criteria for successful
      block with mean strength reduction of 82.2% (SD, 21.6%) at 15 mins. Blocks were
      completed in 122 secs (SD, 33 secs). CONCLUSIONS: Obturator nerve block using USG
      to achieve interfascial injection without nerve stimulation had success similar
      to that reported in studies using nerve stimulation.

PMID- 19587626
TI  - Ultrasound improves the success rate of a tibial nerve block at the ankle.
AB  - BACKGROUND: The tibial nerve provides the majority of sensation to the foot.
      Although multiple techniques have been described, there exists little evidence
      based medicine evaluating different techniques for blocking the tibial nerve at
      the ankle. We hypothesized that an ultrasound (US)-guided tibial nerve block at
      the ankle would prove more successful than a conventional approach based on
      surface landmarks. METHODS: Eighteen healthy volunteers were prospectively
      randomized into this controlled and blinded study. Each subject was placed prone,
      and one ankle was randomly assigned to receive either an US-guided tibial nerve
      block (group US) or a traditional landmark-based tibial nerve block (group LM).
      The subject's other ankle then received the alternate approach. All blocks were
      performed with 5 mL of 3% chloroprocaine. We evaluated sensory and motor blocks.
      A successful block was defined as complete loss of sensation to both ice and
      pinprick at 5 cutaneous sites. Secondary outcome variables included performance
      times, number of needle passes, participant satisfaction, and presence of any
      complications. RESULTS: At 30 mins, the block was complete in 72% of participants
      in group US as compared with 22% in group LM. At all times, the proportion of
      complete blocks was higher in group US. Ultrasound-guided blocks took longer on
      average to perform than traditional blocks (159 vs 79 secs; P < 0.001). There
      were more needle redirects in group US, with 8 subjects requiring 3 or more
      redirects versus none in group LM. Subjects preferred the US block 78% of the
      time (95% confidence interval, 52%-95%). CONCLUSIONS: In healthy volunteers, US
      guidance results in a more successful tibial nerve block at the ankle than does a
      traditional approach using surface landmarks.

PMID- 19587628
TI  - Ultrasound of the lateral femoral cutaneous nerve: normal findings in a cadaver
      and in volunteers.
AB  - OBJECTIVE: To assess the feasibility of ultrasound (US) in visualizing the
      lateral femoral cutaneous nerve (LFCN) in a cadaver and 8 volunteers. METHODS:
      Ultrasound and US-guided dye injection was performed in 1 cadaver to show the
      feasibility of detecting the LFCN. We then performed US in 8 volunteers to assess
      position of the nerve in respect to the anterior iliac spine. We subsequently
      performed US-guided anesthetic block of the LFCN on both sides with 0.3 mL local
      anesthetic. Success rate, time to maximum peak blockade, and duration of blockade
      were noted. RESULTS: Ultrasound allowed visualization of the LFCN in the
      cadaveric specimen on both sides and in all but 1 volunteer. Ultrasound-guided
      block of the LFCN was successful in all but 1 volunteer. The mean distance of
      LFCN from the anterior iliac spine was 2.9 cm on the right side and 2.8 cm on the
      left side. The mean duration of the block was 4.4 hours. CONCLUSION: Ultrasound
      enables visualization of the LFCN in a cadaver and in volunteers. Ultrasound
      guided injection successfully blocked the LFCN.

PMID- 19587629
TI  - Neurofibromatosis: advances in molecular genetics, diagnosis, and treatment.
      Introduction.

PMID- 19587630
TI  - The Neurofibromatoses. Part 1: NF1.
AB  - The neurofibromatoses, including neurofibromatosis 1 (NF1), neurofibromatosis 2
      (NF2), and schwannomatosis, comprise a group of genetically distinct disorders of
      the nervous system unified by the predisposition to nerve sheath tumors. NF1 is
      the most common neurogenetic disorder, with a birth incidence of 1 in 3000. NF1
      is inherited in auto-somal dominant fashion with full penetrance and variable
      expressivity. The hallmark lesion of NF1 is the neurofibroma, a benign tumor
      derived from the nerve sheath and composed of a mixture of proliferating Schwann
      cells, fibroblasts, mast cells, and pericytes. Other findings include gliomas,
      learning disability, vasculopathy, and bony abnormalities. Cafe au lait macules
      are typically the initial clinical manifestation of NF1 and tend to increase in
      size and number throughout childhood and puberty. Current treatment of patients
      with NF1 remains primarily surgical. Genetic counseling is essential for adult
      patients because molecular diagnostic testing can minimize the risk of
      transmission to children.

PMID- 19587631
TI  - Intramedullary spinal cord hemorrhage (hematomyelia).
AB  - Intramedullary spinal cord hemorrhage (hematomyelia) is an uncommon cause of
      myelopathy and can present in an acute, subacute, stepwise, or chronic fashion.
      Spinal vascular malformations such as intramedullary cavernomas and intradural
      arteriovenous malformations are the most common cause of atraumatic
      intramedullary spinal cord hemorrhage based on the existing literature.
      Additional considerations include warfarin or heparin anticoagulation, hereditary
      or acquired bleeding disorders, primary spinal cord tumors, spinal cord
      metastases, Gowers' intrasyringal hemorrhage, or a delayed complication of spinal
      radiation. Prompt diagnosis of hematomyelia first requires recognition of a
      myelopathy syndrome (transverse, central, anterior, posterior, or hemi-cord)
      often accompanied by sudden, severe back or neck pain and sometimes radicular
      pain. MRI with and without gadolinium is the preferred imaging modality. There
      are no clinical trials to guide the management of acute intramedullary spinal
      cord hemorrhage, and subsequent treatment is usually directed toward the
      underlying cause.

PMID- 19587632
TI  - Contraception for women with epilepsy.
AB  - The choice of a contraceptive drug can be challenging for women with epilepsy due
      to possible interactions between antiepileptic drugs (AEDs) and hormonal
      contraception. Enzyme-inducing AEDs can cause hormonal contraception to fail and
      can increase the risk of teratogenicity. Higher doses of oral contraceptives can
      overcome pharmacologic failure but may create additional risks. The effects of
      reproductive hormones on individual AEDs have recently been clarified, providing
      helpful guidelines for physicians and patients. Studies show that lamotrigine has
      a significantly increased clearance (> 50%) when used with combined oral
      contraceptives, which results in an increased seizure frequency in most patients.
      Useful alternatives to oral contraceptives include depot injections and
      intrauterine devices. Subdermal implants may increase the risk of pregnancy in
      women with epilepsy on enzyme-inducing AEDs. Depot medroxyprogesterone acetate is
      effective but can increase side effects. Intrauterine devices are an alternative
      to pharmacologic approaches because they lack drug-drug interactions and side
      effects.

PMID- 19587633
TI  - Neuroimaging advances. Highlights from the 32nd Annual Meeting of the American
      Society of Neuroimaging, January 22-25, 2009, Orlando, FL.

PMID- 19587634
TI  - International Stroke Conference 2009. Highlights From the International Stroke
      Conference 2009, February 18-20, 2009, San Diego, CA.

PMID- 19587635
TI  - Multiple brain infarcts after orbital inflammation.
AB  - A 75-year-old woman developed trigeminal varicella-zoster virus infection
      complicated by ophthalmoplegia, and visual loss followed by recurrent cerebral
      infarctions involving small and large intracranial arteries. Medical therapy
      improved her ophthalmoplegia, but she developed a right hemiparesis and aphasia.

PMID- 19587636
TI  - Migraine: migraine headache pathogenesis in historical perspective.

PMID- 19587637
TI  - Re: Multiple brain infarcts after orbital inflammation.

PMID- 19587638
TI  - Natural killer T cells and the regulation of asthma.
AB  - A crucial role has been suggested for invariant natural killer T cells (iNKT) in
      regulating the development of asthma, a complex and heterogeneous disease
      characterized by airway inflammation and airway hyperreactivity (AHR). iNKT cells
      constitute a unique subset of T cells responding to endogenous and exogenous
      lipid antigens, rapidly secreting a large amount of cytokines, which amplify both
      innate and adaptive immunity. Herein, we review recent studies showing a
      requirement for iNKT cells in various models of asthma in mice and monkeys as
      well as studies in human patients. Surprisingly, in several different murine
      models of asthma, distinct subsets of iNKT cells were required, suggesting that
      iNKT cells serve as a common critical pathogenic element for many different forms
      of asthma. The importance of iNKT cells in both allergic and non-allergic forms
      of asthma, which are independent of adaptive immunity and associated with airway
      neutrophils, may explain situations previously found to be incompatible with the
      Th2 paradigm of asthma.

PMID- 19587641
TI  - NKT cells in mucosal immunity.
AB  - The gastrointestinal tract allows the residence of an almost enumerable number of
      bacteria. To maintain homeostasis, the mucosal immune system must remain tolerant
      to the commensal microbiota and eradicate pathogenic bacteria. Aberrant
      interactions between the mucosal immune cells and the microbiota have been
      implicated in the pathogenesis of inflammatory disorders, such as inflammatory
      bowel disease (IBD). In this review, we discuss the role of natural killer T
      cells (NKT cells) in intestinal immunology. NKT cells are a subset of non
      conventional T cells recognizing endogenous and/or exogenous glycolipid antigens
      when presented by the major histocompatibility complex (MHC) class I-like antigen
      presenting molecules CD1d and MR1. Upon T-cell receptor (TCR) engagement, NKT
      cells can rapidly produce various cytokines that have important roles in mucosal
      immunity. Our understanding of NKT-cell-mediated pathways including the
      identification of specific antigens is expanding. This knowledge will facilitate
      the development of NKT cell-based interventions and immune therapies for human
      intestinal diseases.

PMID- 19587640
TI  - HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG
      seronegative individuals block HIV-1 epithelial transcytosis and neutralize
      CD4(+) cell infection: an IgA gene and functional analysis.
AB  - AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues
      are the primary sites of natural human immunodeficiency virus type-1 (HIV-1)
      transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope
      gp41 subunit is one correlate of protection in individuals who are highly
      sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS).
      Understanding these peculiar IgAs at the gene and functional level is possible
      only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from
      HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in
      vitro, are transcytosis-blocking and infection-neutralizing. Characterization of
      their IgA genes shows that Fab specific for the gp41 membrane-proximal region
      harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly
      neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected
      Fab IgA shows extensive somatic mutations that cluster in the CDR regions,
      indicating that affinity maturation due to an antigen-driven process had occurred
      in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of
      HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function
      (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing
      monoclonal IgAs could be used in microbicide formulation.

PMID- 19587639
TI  - Th17 cells at the crossroads of innate and adaptive immunity against infectious
      diseases at the mucosa.
AB  - T helper type 17 (Th17) cells are a distinct lineage of T cells that produce the
      effector molecules IL-17, IL-17F, IL-21, and IL-22. Although the role of Th17
      cells in autoimmunity is well documented, there is growing evidence that the Th17
      lineage and other interleukin (IL)-17-producing cells are critical for host
      defense against bacterial, fungal, and viral infections at mucosal surfaces. Here
      we summarize recent progress in our understanding of the function of IL-17
      producing cells as a bridge between innate and adaptive immunity against
      infectious diseases at the mucosa.

PMID- 19587643
TI  - Warfarin interactions with substances listed in drug information compendia and in
      the FDA-approved label for warfarin sodium.
AB  - Interactions of warfarin with other drugs or substances can pose a serious
      problem. We assessed three drug information compendia-Clinical Pharmacology,
      ePocrates, and Micromedex-and the warfarin sodium (Coumadin) product label
      (August 2007) approved by the US Food and Drug Administration for listings of
      interactions between warfarin and drugs, biologics, foods, and dietary
      supplements. The drug information compendia and warfarin label differed greatly
      as to the total number of substances that interact with warfarin. Of a total of
      648 entries from the four sources, only 50 were common to all the sources. The
      types of substances listed as interacting with warfarin were entire classes of
      drugs, individual drugs, and combinations; biologics; dietary supplements; foods;
      alcohol; and tobacco. These sources were then examined for classification by
      severity of interaction and the underlying evidence base. This study provides
      evidence that there is little concordance among commonly used drug compendia and
      product labels with respect to interactions involving warfarin.

PMID- 19587642
TI  - Pharmacokinetic, pharmacodynamic, and safety profile of a new cholesteryl ester
      transfer protein inhibitor in healthy human subjects.
AB  - A new cholesteryl ester (CE) transfer protein (CETP) inhibitor (CP-800,569) was
      evaluated. Doses of 30-1,800 mg were administered once daily to healthy subjects
      for 14 days. Serum CP-800,569 levels increased, and CETP activity decreased, in a
      dose-related manner. Serum levels of high-density lipoprotein (HDL) increased (by
      a maximum of 156%), and those of low-density lipoprotein (LDL) decreased (by a
      maximum of 47%). CP-800,569 also had the effect of lowering postprandial
      triglyceride levels. Trough concentrations of apolipoprotein E (apoE) increased:
      the maximum increases were 89% for total plasma apoE and 280% for HDL apoE. By
      contrast, the postprandial increases in total plasma levels of apoE and non HDL
      apoE were either diminished by CP-800,569 or reversed to decreases. CP-800,569
      was very well tolerated, with some nonserious gastrointestinal adverse events
      seen only with the 1,800-mg dose. No changes in blood pressure (BP) were
      observed. The possible effects of higher CP-800,569 doses on aldosterone and
      cortisol levels could not be excluded. The results of this study may be useful in
      CP-800,569 dose selection.

PMID- 19587644
TI  - Credit where credit is overdue.

PMID- 19587645
TI  - Sanofi Aventis grooms its ranks for biotech partnering.

PMID- 19587646
TI  - Governments fiddle while biotech burns.

PMID- 19587651
TI  - Diagnostics firms face new patent claim worries.

PMID- 19587655
TI  - iZumi's plans to capitalize on iPS cells.

PMID- 19587654
TI  - Report claims no yield advantage for Bt crops.

PMID- 19587656
TI  - Up in arms.

PMID- 19587657
TI  - PRIDE Converter: making proteomics data-sharing easy.

PMID- 19587658
TI  - NCBI Peptidome: a new public repository for mass spectrometry peptide
      identifications.

PMID- 19587659
TI  - More eyeballs on AERS.

PMID- 19587660
TI  - Lessons in biopolitics.

PMID- 19587661
TI  - Metabolic reconfiguration precedes transcriptional regulation in the antioxidant
      response.

PMID- 19587663
TI  - Dynamics of global disclosure through patent and journal publications for
      biopharmaceutical products.

PMID- 19587662
TI  - Developing safe therapies from human pluripotent stem cells.

PMID- 19587665
TI  - Minicells overcome tumor drug-resistance.

PMID- 19587666
TI  - Biomarker validation by targeted mass spectrometry.

PMID- 19587669
TI  - Fifteen years of microbial genomics: meeting the challenges and fulfilling the
      dream.
AB  - As we approach the completed sequencing of 1,000 microbial genomes, the field of
      microbial genomics is poised at a crossroads. The future holds great promise for
      far-reaching advancements in microbiology as well as in diverse, related
      sciences. But realizing that potential will require meeting the challenges that
      have accompanied the rapid development of the underlying technology and the
      exponential growth of data. New technologies provide unprecedented opportunities
      but also call for conceptual shifts. Experience gained in the first decade of
      genomics can guide the improved approaches now needed for the selection of genome
      sequencing projects and their funding, for genome publication and annotation, as
      well as for data analysis and access. Equipped with these new tools and policies,
      microbiologists will have a unique opportunity for unprecedented exploration of
      our microbial planet.

PMID- 19587667
TI  - The importance of being red.

PMID- 19587678
TI  - Nonconformity in ubiquitin compliance.

PMID- 19587679
TI  - A histone code for the DNA damage response in mammalian cells?

PMID- 19587680
TI  - Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.
AB  - Inhibition of the TOR signalling pathway by genetic or pharmacological
      intervention extends lifespan in invertebrates, including yeast, nematodes and
      fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in
      a mammalian species was unknown. Here we report that rapamycin, an inhibitor of
      the mTOR pathway, extends median and maximal lifespan of both male and female
      mice when fed beginning at 600 days of age. On the basis of age at 90% mortality,
      rapamycin led to an increase of 14% for females and 9% for males. The effect was
      seen at three independent test sites in genetically heterogeneous mice, chosen to
      avoid genotype-specific effects on disease susceptibility. Disease patterns of
      rapamycin-treated mice did not differ from those of control mice. In a separate
      study, rapamycin fed to mice beginning at 270 days of age also increased survival
      in both males and females, based on an interim analysis conducted near the median
      survival point. Rapamycin may extend lifespan by postponing death from cancer, by
      retarding mechanisms of ageing, or both. To our knowledge, these are the first
      results to demonstrate a role for mTOR signalling in the regulation of mammalian
      lifespan, as well as pharmacological extension of lifespan in both genders. These
      findings have implications for further development of interventions targeting
      mTOR for the treatment and prevention of age-related diseases.

PMID- 19587681
TI  - The late Precambrian greening of the Earth.
AB  - Many aspects of the carbon cycle can be assessed from temporal changes in the
      (13)C/(12)C ratio of oceanic bicarbonate. (13)C/(12)C can temporarily rise when
      large amounts of (13)C-depleted photosynthetic organic matter are buried at
      enhanced rates, and can decrease if phytomass is rapidly oxidized or if low (13)C
      is rapidly released from methane clathrates. Assuming that variations of the
      marine (13)C/(12)C ratio are directly recorded in carbonate rocks, thousands of
      carbon isotope analyses of late Precambrian examples have been published to
      correlate these otherwise undatable strata and to document perturbations to the
      carbon cycle just before the great expansion of metazoan life. Low (13)C/(12)C in
      some Neoproterozoic carbonates is considered evidence of carbon cycle
      perturbations unique to the Precambrian. These include complete oxidation of all
      organic matter in the ocean and complete productivity collapse such that low
      (13)C/(12)C hydrothermal CO(2) becomes the main input of carbon. Here we compile
      all published oxygen and carbon isotope data for Neoproterozoic marine
      carbonates, and consider them in terms of processes known to alter the isotopic
      composition during transformation of the initial precipitate into
      limestone/dolostone. We show that the combined oxygen and carbon isotope
      systematics are identical to those of well-understood Phanerozoic examples that
      lithified in coastal pore fluids, receiving a large groundwater influx of
      photosynthetic carbon from terrestrial phytomass. Rather than being perturbations
      to the carbon cycle, widely reported decreases in (13)C/(12)C in Neoproterozoic
      carbonates are more easily interpreted in the same way as is done for Phanerozoic
      examples. This influx of terrestrial carbon is not apparent in carbonates older
      than approximately 850 Myr, so we infer an explosion of photosynthesizing
      communities on late Precambrian land surfaces. As a result, biotically enhanced
      weathering generated carbon-bearing soils on a large scale and their detrital
      sedimentation sequestered carbon. This facilitated a rise in O(2) necessary for
      the expansion of multicellular life.

PMID- 19587685
TI  - Brain potentials related to the human penile erection.
AB  - The aim of this study was to elucidate the brain processes preceding penile
      responses. Electroencephalographic (EEG) potentials and penile circumference were
      recorded simultaneously while male subjects were exposed to visual sexual stimuli
      (VSS). The trials were sorted by the penile response of the subjects (erection,
      maintenance or detumescence). The corresponding EEG recordings were then
      subjected to independent component analysis. We found that 200 ms after VSS onset
      brain potentials differ according to the genital response to follow. Whereas
      early posterior negativity (EPN) was predominantly related to erection and
      maintenance, P3-like activity was found to precede detumescence. EPN indicates a
      more 'emotional' processing state of the brain, whereas P3-like activity related
      to detumescence indicates a more 'cognitive' processing state. The latter is
      assumed to reflect activity of the locus coeruleus-norepinephrine system. Further
      research should evaluate the contribution of P3-related brain activity to
      psychogenic erectile dysfunction.

PMID- 19587682
TI  - Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
AB  - An open chromatin largely devoid of heterochromatin is a hallmark of stem cells.
      It remains unknown whether an open chromatin is necessary for the differentiation
      potential of stem cells, and which molecules are needed to maintain open
      chromatin. Here we show that the chromatin remodelling factor Chd1 is required to
      maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a
      euchromatin protein that associates with the promoters of active genes, and
      downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient
      embryonic stem cells are no longer pluripotent, because they are incapable of
      giving rise to primitive endoderm and have a high propensity for neural
      differentiation. Furthermore, Chd1 is required for efficient reprogramming of
      fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is
      essential for open chromatin and pluripotency of embryonic stem cells, and for
      somatic cell reprogramming to the pluripotent state.

PMID- 19587683
TI  - A highly annotated whole-genome sequence of a Korean individual.
AB  - Recent advances in sequencing technologies have initiated an era of personal
      genome sequences. To date, human genome sequences have been reported for
      individuals with ancestry in three distinct geographical regions: a Yoruba
      African, two individuals of northwest European origin, and a person from China.
      Here we provide a highly annotated, whole-genome sequence for a Korean
      individual, known as AK1. The genome of AK1 was determined by an exacting,
      combined approach that included whole-genome shotgun sequencing (27.8x coverage),
      targeted bacterial artificial chromosome sequencing, and high-resolution
      comparative genomic hybridization using custom microarrays featuring more than 24
      million probes. Alignment to the NCBI reference, a composite of several ethnic
      clades, disclosed nearly 3.45 million single nucleotide polymorphisms (SNPs),
      including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion
      polymorphisms (indels). SNP and indel densities were strongly correlated genome
      wide. Applying very conservative criteria yielded highly reliable copy number
      variants for clinical considerations. Potential medical phenotypes were annotated
      for non-synonymous SNPs, coding domain indels, and structural variants. The
      integration of several human whole-genome sequences derived from several ethnic
      groups will assist in understanding genetic ancestry, migration patterns and
      population bottlenecks.

PMID- 19587687
TI  - Impact of clean delivery kit use on clean delivery practices in Beni Suef
      Governorate, Egypt.
AB  - OBJECTIVE: A major factor contributing to neonatal and maternal infections is
      unhygienic delivery practices. This study explores the impact of clean delivery
      kit (CDK) use on clean delivery practices during home and facility deliveries.
      DESIGN: Kits were distributed from primary care facilities and mothers and birth
      attendants received training on kit importance and use. The study was designed as
      a cross-sectional cohort study. Raedat (community health workers) visited 349
      women during the postpartum period to administer a structured questionnaire.
      SETTING: The study was conducted from mid-March through mid-July 2001 in two
      rural areas of Ihnasia district in Beni Suef Governorate (Upper Egypt). RESULT:
      In bivariate analysis, CDK users in the home were more likely to report that the
      birth attendant had clean hands (P<0.001), washed/wiped the mother's perineum
      (P<0.001), used a sterile cord tie (P=0.001), applied antiseptic to the cord
      after cutting (P<0.001), and used a sterile cord cover (P<0.001) as compared with
      non-CDK users. CDK users at the facility were more likely to report that the
      birth attendant washed/wiped the mothers perineum (P=0.049) and used a sterile
      cord cover (P=0.030) as compared with non-CDK users. CONCLUSION: In settings in
      which unhygienic practices during home as well as facility deliveries are
      prevalent, use of inexpensive CDKs can promote clean delivery practices.

PMID- 19587686
TI  - Intracavernosal pressure characteristics analyzed by power spectral density for
      identifying the phase of penile erection.
AB  - Knowledge of the time course of penile erection is very important to
      understanding erection physiology. The changes in the intracavernosal pressure
      (ICP) and the different phases of an erection are pivotal to the ability to
      produce and maintain a rigid penile erection. This study investigated an
      objective and low-invasiveness method for identifying different erection phases
      based on an innovative ICP analysis technique. Blood infuses into the corpora
      cavernosa and causes the ICP to increase. The ICP usually exhibits tiny
      oscillations at the frequency of the heartbeat when it increases from diastole to
      systole. The characteristic oscillation amplitudes corresponding to the period
      when the full and rigid erection phases begin can be extracted by power spectral
      density analysis. The reliability and accuracy of the proposed method was
      verified by the Bland-Altman graphs indicating a good agreement with the existing
      method that compares the ICP with the arterial pressure. Moreover, all of the
      intraclass correlation coefficient values were close to 1.00, with the lower
      limit of the 95% confidence interval exceeding 0.75. The described novel
      objective and low-invasiveness method can therefore be used for identifying the
      full and rigid erection phases of the penis in urological investigations during
      different erection phases.

PMID- 19587688
TI  - Parathyroid surgery in pregnancy: review of the literature and localization by
      aspiration for parathyroid hormone levels.
AB  - OBJECTIVE: To review the management of primary hyperparathyroidism in pregnant
      women by focusing on the use of preoperative localization procedures and
      minimally invasive parathyroid surgery during pregnancy. STUDY DESIGN: We report
      the clinical course of two pregnant women with severe hypercalcemia due to
      primary hyperparathyroidism, as well as review the literature. RESULTS: Primary
      hyperparathyroidism in pregnant women is associated with high prevalence of
      maternal and neonatal complications. In women, with severe hypercalcemia,
      parathyroid surgery during pregnancy reduces fetal and maternal morbidities.
      Preoperative localization of parathyroid adenomas during pregnancy remains
      challenging. In selected cases aspiration of nodules suspected of being
      parathyroid adenomas with the measurement of the parathyroid hormone (PTH) from
      the aspirate can localize the adenoma, and allow the surgeon to carry out a
      minimally invasive parathyroidectomy. CONCLUSION: Localization of a suspected
      parathyroid adenoma by ultrasound-guided aspiration of a lesion and the
      measurement of the PTH has previously been described in non-pregnant women. Our
      review of the literature did not identify any previous case of a pregnant woman
      with primary hyperparathyroidism, where preoperative localization of a
      parathyroid adenoma was accomplished by aspiration of a suspected lesion followed
      by a successful minimally invasive parathyroidectomy carried out during
      pregnancy.

PMID- 19587691
TI  - Thermal injury causes DNA damage and lethality in unheated surrounding cells:
      active thermal bystander effect.
AB  - Direct heat exposure to cells causes protein degradation and DNA damage, which
      can lead to genetic alteration and cell death, but little is known about heat
      induced effects on the surrounding tissue. After burns or laser surgery, loss of
      viability in the surrounding tissue has been explained by a temperature gradient
      due to heat diffusion. This study shows that, in the absence of any direct
      heating, heat diffusion, or cell-to-cell contact, "bystander" cells that share
      the medium with heat-exposed cells exhibit DNA damage, apoptosis, and loss of
      viability. We coin this phenomenon "active thermal bystander effect" (ATBE).
      Significant ATBE was induced by fibroblasts exposed for 10 minutes to a
      temperature range of 44-50 degrees C (all P<0.011). The ATBE was not induced by
      cells heated to lethality above 54 degrees C and immediate medium exchange did
      not suppress the effect. Therefore, the thermal bystander effect appears to be an
      active process in which viable, heat-injured cells induce a signal cascade and/or
      mediator that damages or kills surrounding bystander cells. The ATBE may have
      clinical relevance for acute burn trauma, hyperthermic treatments, and distant
      tissue damage after localized heat stress.

PMID- 19587690
TI  - Effect of prenatal glucocorticoid treatment on size at birth among infants born
      at term gestation.
AB  - OBJECTIVE: To determine whether prenatal treatment with a single course of
      glucocorticoids (GCs) affects size at birth among full-term infants independent
      of fetal size before GC administration or exposure to preterm labor (PTL). STUDY
      DESIGN: In all, 105 full-term infants were recruited into three study groups (30
      GC treated; 60 controls matched for gestational age (GA) at birth and sex; and 15
      PTL controls without GC exposure). Size of the infants was estimated before
      treatment using two-dimensional (2D) ultrasound and by direct measurement at
      birth. RESULTS: Length, weight and head circumference at birth were smaller among
      GC-treated infants compared with matched controls (P's<0.01), although fetal size
      did not differ before treatment (P's>0.2). Exposure to PTL did not account for
      this effect. CONCLUSIONS: Prenatal treatment with a single course of GCs was
      associated with a reduction in size at birth among infants born at term
      gestation. This effect cannot be explained by differences in fetal size before
      treatment or exposure to PTL.

PMID- 19587689
TI  - Bisphenol-A and disparities in birth outcomes: a review and directions for future
      research.
AB  - Racial disparities in pregnancy outcome in the United States are significant,
      persistent and costly, but the causes are poorly understood. We propose that
      disproportionate exposure of African-American women to environmental endocrine
      disrupting compounds (EDCs) may contribute to birth outcome disparities. Marked
      racial segregation, as well as health behaviors associated with poverty could
      result in differences in exposure to particular EDCs. One EDC that has aroused
      concern in recent years is bisphenol-A (BPA), a widely used industrial
      plasticizer with known estrogenic properties. Published studies indicate that
      excessive BPA exposure is associated with reduced fetal survival, as well as
      reductions in maternal weight and fetal body weight. Related findings include
      adverse effects of BPA exposure on ovarian function, mammary gland development,
      earlier age of puberty onset and some metabolic parameters. However, these
      findings are largely limited to experimental animal studies, and need to be
      validated in human populations. Our review supports the need to move beyond the
      currently dominant toxicological approach to examining the effects of BPA
      exposure, and rely more on observational human studies and epidemiological
      methods. Many of the risk factors for racial disparities in pregnancy outcome are
      global or difficult to modify, but exposure to BPA is a potentially malleable
      risk factor. If BPA contributes to racial disparities in pregnancy outcome, there
      are important implications for prevention. It is our hope that this review will
      stimulate further research in this important and neglected area.

PMID- 19587693
TI  - Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light
      source: clinical correlation with a single-blinded study.
AB  - It has been reported that skin aging is associated with a downregulation in
      collagen synthesis and an elevation in matrix metalloproteinase (MMP) expression.
      This study investigated the potential of light-emitting diode (LED) treatments
      with a 660 nm sequentially pulsed illumination formula in the photobiomodulation
      of these molecules. Histological and biochemical changes were first evaluated in
      a tissue-engineered Human Reconstructed Skin (HRS) model after 11 sham or LED
      light treatments. LED effects were then assessed in aged/photoaged individuals in
      a split-face single-blinded study. Results yielded a mean percent difference
      between LED-treated and non-LED-treated HRS of 31% in levels of type-1
      procollagen and of -18% in MMP-1. No histological changes were observed.
      Furthermore, profilometry quantification revealed that more than 90% of
      individuals showed a reduction in rhytid depth and surface roughness, and, via a
      blinded clinical assessment, that 87% experienced a reduction in the Fitzpatrick
      wrinkling severity score after 12 LED treatments. No adverse events or downtime
      were reported. Our study showed that LED therapy reversed collagen downregulation
      and MMP-1 upregulation. This could explain the improvements in skin appearance
      observed in LED-treated individuals. These findings suggest that LED at 660 nm is
      a safe and effective collagen-enhancement strategy.

PMID- 19587692
TI  - Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant
      melanoma.
AB  - Fatty acid-binding protein-7 (FABP7) has been shown to be expressed in cutaneous
      melanoma; however, its role in tumor progression is unclear. Expression of FABP7
      was assessed during melanoma progression through assessment of various
      clinicopathology stages of primary tumor progression and metastasis. FABP7 mRNA
      was highly expressed in 60 of 87 (69%) primary melanomas, compared with
      significant (P<0.0001) reduction in 13 of 68 (19%) metastatic melanomas. Analysis
      of 37 paired primary and metastatic melanomas by immunohistochemistry with anti
      FABP7 Ab showed 73 and 27% positivity, respectively (P<0.001). FABP7 detection of
      metastatic tissues was inversely correlated with relapse-free (P<0.0001) and
      overall (P<0.0001) survival. To examine FABP7 expression loss in advanced
      melanomas, loss of heterozygosity (LOH) was assessed using microsatellite markers
      encompassing the FABP7 gene. LOH was identified in 10 of 20 (50%) metastatic
      melanomas at 6q22.31, compared with 0 of 14 primary melanomas (P=0.0017). FABP7
      as a surrogate biomarker for circulating tumor cells (CTCs) in the blood was
      assessed by quantitative real-time (qRT)-PCR from melanoma patients' blood
      (n=134). Assessment of patients' blood showed that FABP7(+) CTC decreased with
      disease progression. FABP7 may function as a tumor progression gene and can be
      used as a potential diagnostic biomarker of early-stage melanoma systemic
      spreading in blood.

PMID- 19587694
TI  - Active transport of contact allergens and steroid hormones in epidermal
      keratinocytes is mediated by multidrug resistance related proteins.

PMID- 19587695
TI  - Improvement of nerve regeneration in tissue-engineered skin enriched with schwann
      cells.
AB  - The incorporation of Schwann cells in reconstructed skin (RS) could have a major
      role in achieving functional recovery of cutaneous sensory perception. We showed
      with a unique in vitro model of a tissue-engineered innervated reconstructed
      dermis that Schwann cells promoted a twofold increase in the number of sensory
      neurites migrating in the three-dimensional tissue as compared with the control.
      In addition, Schwann cells spontaneously colocalized along neurites and achieved
      the formation of myelin sheaths in vitro as assessed by transmission electron
      microscopy. We prepared RS samples enriched or not with Schwann cells and
      transplanted them on nude mice for 60-90 days. We demonstrated that Schwann cells
      induced a 1.8- and 1.7-fold increase in the number of nerve fibers migrating in
      the graft 60 and 90 days after transplantation, respectively. In addition, the RS
      sample enriched with Schwann cells had a current perception threshold similar to
      that of normal skin for the large and myelinated Abeta-sensory fibers, in
      contrast with the control. Thus, we showed that the addition of Schwann cells to
      tissue-engineered skin not only enhanced nerve migration but also promoted myelin
      sheath formation in vitro and nerve function recovery in vivo.

PMID- 19587696
TI  - Autoantigens in vitiligo identified by the serological selection of a phage
      displayed melanocyte cDNA expression library.
AB  - Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by
      circumscribed depigmented macules resulting from the loss of cutaneous
      melanocytes. Although the exact cause of vitiligo remains obscure, autoimmunity
      may play a role in the development of the disease. The present study was
      undertaken to investigate the applicability of phage display technology to
      identify B-cell autoantigens in vitiligo. A melanocyte cDNA phage display library
      was subjected to rounds of enrichment with vitiligo patient IgG. Subsequently,
      enriched IgG-binding peptides representing putative autoantigens were identified
      by sequencing their encoding cDNAs. Radioimmunoassays were used to confirm the
      immunoreactivity of vitiligo patient (n=61) and control (n=28) sera to several of
      the putative autoantigens. Non-segmental vitiligo patient sera (n=53) were
      positive for antibody (Ab) reactivity to gamma-enolase (8%); alpha-enolase (9%);
      heat-shock protein 90 (13%); osteopontin (4%); ubiquitin-conjugating enzyme
      (15%); translation-initiation factor 2 (6%); and GTP-binding protein, Rab38
      (15%). Ab reactivity to at least one of the previously unknown autoantigens was
      detected in 51% of patients with non-segmental vitiligo. In contrast, Ab
      reactivity in a group of patients with segmental vitiligo (n=8) was not
      demonstrated. Overall, the study indicated that the targets of autoantibodies in
      vitiligo patients can be revealed by employing the methodology of phage display.

PMID- 19587697
TI  - Non-steroidal anti-inflammatory drugs and melanoma risk: large Dutch population
      based case-control study.
AB  - This case-control study investigates the potential chemoprophylactic properties
      of non-steroidal anti-inflammatory drugs (NSAIDs) on the incidence of cutaneous
      melanoma (CM). Data were extracted from the Dutch PHARMO pharmacy database and
      the PALGA pathology database. Cases had a primary CM between 1991 and 2004, were
      >or=18 years, and were observed for 3 years in PHARMO before diagnosis. Controls
      were matched for date of birth, gender, and geographical region. NSAIDs and
      acetylsalicylic acids (ASAs) were analyzed separately. Adjusted odds ratio (OR)
      and 95% confidence interval (CI) were calculated using multivariable logistic
      regression, and the results were stratified across gender. A total of 1,318 CM
      cases and 6,786 controls were eligible to enter the study. CM incidence was not
      significantly associated with ever ASA use (adjusted OR: 0.92, 95% CI: 0.76-1.12)
      or ever non-ASA NSAID use (adjusted OR: 1.10, 95% CI: 0.97-1.24). However,
      continuous use of low-dose ASAs was associated with a significant reduction of CM
      risk in women (adjusted OR: 0.54, 95% CI: 0.30-0.99) but not in men (OR: 1.01,
      95% CI: 0.69-1.47). A significant trend (P=0.04) from no use, non-continuous use
      to continuous use was observed in women. Continuous use of low-dose ASAs may be
      associated with a reduced incidence of CM in women, but not in men.

PMID- 19587698
TI  - The keratins of the human beard hair medulla: the riddle in the middle.
AB  - We have investigated the expression of 52 of the 54 keratins in beard hair
      medulla. We found that not only 12 hair keratins but, unexpectedly, also 12
      epithelial keratins are potentially expressed in medulla cells. The latter
      comprise keratins also present in outer- and inner-root sheaths and in the
      companion layer. Keratins K5, K14, K17, K25, K27, K28, and K75 define a "pre
      medulla," composed of cells apposed to the upper dermal papilla. Besides K6, K16,
      K7, K19, and K80, all pre-medullary epithelial keratins continue to be expressed
      in the medulla proper, along with the 12 hair keratins. Besides this unique
      feature of cellular keratin co-expression, the keratin pattern itself is highly
      variable in individual medulla cells. Remarkably, both epithelial and hair
      keratins behave highly promiscuously with regard to heterodimer- and IF
      formation, which also includes keratin chain interactions in IF bundles. We also
      identified cortex cells within the medullary column. These exhibit all the
      properties of genuine cortex cells, including a particular type of keratin
      heterogeneity of their compact IF bundles. In both keratin expression profile and
      keratin number, medulla cells are distinct from all other cells of the hair
      follicle or from any other epithelium.

PMID- 19587699
TI  - Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and
      type II diabetes.
AB  - Psoriasis is an immune-mediated skin disorder, which is inherited as a complex
      trait. Genome-wide linkage and association studies have identified a major
      disease susceptibility locus on chromosome 6p21, as well as a number of genetic
      determinants of smaller effect. Our group has also documented a significant
      association between psoriasis and CDKAL1, a gene previously implicated in the
      pathogenesis of Crohn's disease (CD) and type II diabetes (TIID). With this
      study, we validate this association, through the analysis of CDKAL1 single
      nucleotide polymorphism (SNP) rs6908425 in an independently ascertained psoriasis
      dataset (replication sample: 1323 cases vs 1368 controls, P=0.00012, odds ratio
      (OR): 1.28; combined sample: 2579 cases vs 4306 controls, P=4 x 10(-6), OR:
      1.26). We also show that the association with psoriasis and CD is completely
      independent from that with TIID. Finally, we report the results of expression
      studies demonstrating that CDKAL1 transcripts are virtually absent from skin
      keratinocytes, but are abundantly expressed in immune cells, especially in CD4+
      and CD19+ lymphocytes. It is to be noted that our data indicate that CDKAL1
      becomes markedly downregulated when immune cells are activated with proliferating
      signals. Taken together, our results document the presence of allelic
      heterogeneity at the CDKAL1 locus and suggest that CDKAL1 alleles may confer
      susceptibility to clinically distinct disorders through differential effects on
      disease-specific cell types.

PMID- 19587700
TI  - An overview of the Guangzhou biobank cohort study-cardiovascular disease
      subcohort (GBCS-CVD): a platform for multidisciplinary collaboration.
AB  - The Guangzhou Biobank Cohort Study (GBCS, n=30 519, age >or=50 years) was
      established to examine the effects of genetic and environmental influences on
      health problems and chronic disease development. Guangzhou is undergoing massive
      economic development, but from a baseline that had remained unchanged for
      millennia. The Cardiovascular Disease Subcohort (GBCS-CVD) consists of 2000
      participants who have been intensively phenotyped including a range of surrogate
      markers of vascular disease, including carotid artery intima-media thickness,
      cerebral artery stenoses, arterial stiffness, ankle-to-brachial blood pressure
      index and albuminuria, as well as coagulatory and inflammatory markers. Plasma
      and leukocytes are stored in liquid nitrogen for future studies. Preliminary
      demographic data show the female volunteers are younger than the male ones, but
      present with greater levels of adiposity including central obesity (31 vs 16%).
      Women had more body fat (33 vs 24%) and associated levels of adipokines. Despite
      this, body mass index and hip circumferences were similar, which contrasts with
      Caucasian populations. Men had more physician-diagnosed vascular disease (6.1 vs
      2.5%), hypertension (42 vs 34%) and hyperglycaemia (36.6 vs 29.6%) than the
      women, but were less insulin resistant. In men, smoking (40 vs 2%) and drinking
      alcohol (67 vs 50%) was more common and they also had lower energy expenditures.
      The genotype distributions of the 15 typed single nucleotide polymorphisms were
      all in Hardy-Weinberg equilibrium. This article describes the rationale and
      methodology for the study. Given the comprehensive characterization of
      demographic and psychosocial determinants and biochemistry, the study provides a
      unique platform for multidisciplinary collaboration in a highly dynamic setting.

PMID- 19587701
TI  - The optimal home blood pressure monitoring schedule based on the Didima outcome
      study.
AB  - This study investigated the optimal schedule for home blood pressure (HBP)
      monitoring that has the greatest prognostic ability and provides the most
      reliable assessment of HBP. The Didima study assessed the value of HBP (duplicate
      morning and evening measurements, 3 days) in predicting cardiovascular events in
      the general population (662 adults, 8.2+/-0.2 years follow-up). Criteria for the
      optimal monitoring schedule were stabilization of mean HBP, its variability
      (standard deviation (s.d.)) and hazard ratios (HRs) of cardiovascular events per
      1 mm Hg HBP increase. By averaging more readings (1-12), there was a progressive
      decline in average HBP and its s.d. and increase in HR, with most of these
      benefits achieved on the second day (8 readings) and little additional benefit
      obtained on the third day (12 readings). The first day gave higher and more
      unstable HBP values (higher s.d.) with less prognostic ability (lower HR). The
      first HBP readings per occasion gave higher values but with similar prognostic
      ability as the second readings taken 1 min later. There was little difference in
      average HBP between morning and evening readings with no prognostic superiority
      of morning readings. In conclusion, by averaging more readings the average HBP
      and its variability are reduced and the prognostic ability improved. Any aspect
      of HBP monitoring (first or second readings, morning or evening) has similar
      prognostic ability. The first day gives higher and unstable values with lower
      prognostic ability and should be better discarded. These data validate the HBP
      monitoring schedule proposed by the European Society of Hypertension.

PMID- 19587703
TI  - Inhibition of the hTERT promoter by the proto-oncogenic protein TAL1.
AB  - Telomerase activity, which has fundamental roles in development and
      carcinogenesis, strongly depends on the expression of human telomerase reverse
      transcriptase (hTERT), its catalytic subunit. In this report, we show that the
      basic helix-loop-helix factor, TAL1 (T-cell acute lymphoblastic leukemia 1), is a
      negative regulator of the hTERT promoter. Indeed, TAL1 overexpression leads to a
      decrease in hTERT mRNA abundance and hence to reduced telomerase activity.
      Conversely, suppression of TAL1 by RNA interference in Jurkat cells increases
      hTERT expression. Analysis by chromatin immunoprecipitation assays showed that
      TAL1 binds to the hTERT proximal promoter and recruits HDAC1. Considering the
      relationship recently established between TAL1 and the human T-cell leukemia
      virus type 1 (HTLV-1) Tax protein, which was confirmed in T lymphocyte clones
      derived from adult T-cell leukemia patients, we analyzed the effect of TAL1 with
      respect to the earlier characterized effects of Tax and HBZ (HTLV-1 basic leucine
      zipper) on hTERT expression. TAL1 was observed to reinforce the negative effect
      of Tax, whereas hTERT transactivation by the HBZ-JunD complex was repressed by
      TAL1 overexpression. Moreover, HBZ was found to induce proteasome-mediated
      degradation of TAL1. These observations support a model in which Tax and TAL1 by
      repressing hTERT would initially favor genomic instability, whereas expression of
      factors such as HBZ allows at a later stage an increase in hTERT production and
      consequently in telomerase activity.

PMID- 19587702
TI  - PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic
      leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1
      fusion genes: a GRAALL study.
AB  - Adult and child B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) differ
      in terms of incidence and prognosis. These disparities are mainly due to the
      molecular abnormalities associated with these two clinical entities. A genome
      wide analysis using oligo SNP arrays recently demonstrated that PAX5 (paired-box
      domain 5) is the main target of somatic mutations in childhood BCP-ALL being
      altered in 38.9% of the cases. We report here the most extensive analysis of
      alterations of PAX5 coding sequence in 117 adult BCP-ALL patients in the unique
      clinical protocol GRAALL-2003/GRAAPH-2003. Our study demonstrates that PAX5 is
      mutated in 34% of adult BCP-ALL, mutations being partial or complete deletion,
      partial or complete amplification, point mutation or fusion gene. PAX5
      alterations are heterogeneous consisting in complete loss in 17%, focal deletions
      in 10%, point mutations in 7% and translocations in 1% of the cases. PAX5
      complete loss and PAX5 point mutations differ. PAX5 complete loss seems to be a
      secondary event and is significantly associated with BCR-ABL1 or TCF3-PBX1 fusion
      genes and a lower white blood cell count.

PMID- 19587704
TI  - Patterns of monoclonal gammopathy of undetermined significance and multiple
      myeloma in various ethnic/racial groups: support for genetic factors in
      pathogenesis.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is one of the most
      common premalignant disorders in Western countries. Recent studies show that
      almost every multiple myeloma (MM) case is preceded by an MGUS stage.
      Interestingly, prevalence and incidence patterns for MGUS and MM show striking
      disparity patterns across ethnic/racial groups, most notably the two- to
      threefold increase in both these disorders in African Americans compared with
      Caucasians. In contrast, studies on Asian patients show lower
      prevalence/incidence for MGUS/MM compared with Caucasians. Familial aggregation
      for both MGUS and MM has been observed; the risk for MGUS or MM in family members
      with these disorders is increased about two- to three fold compared with the
      general population. Although underlying mechanisms remain unclear, there is
      evidence of heterogeneity among MGUS patients from different ethnic/racial
      groups. For example, compared with Caucasians, African-American and African MGUS
      patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus
      IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This
      review focuses on racial disparity and familial aggregation patterns for MGUS and
      MM and discusses how these observations provide novel clues with regard to
      pathogenesis.

PMID- 19587705
TI  - Increased expression of macrophage inflammatory protein-1alpha on trephine
      biopsies correlates with extensive bone disease, increased angiogenesis and
      advanced stage in newly diagnosed patients with multiple myeloma.

PMID- 19587706
TI  - Soluble decoy receptor 3 modulates the survival and formation of osteoclasts from
      multiple myeloma bone disease patients.
AB  - Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor
      superfamily, is known to be involved in cell survival and osteoclast (OC)
      formation. In this study, we show that malignant plasma cells and T lymphocytes
      from multiple myeloma (MM) bone disease patients, as well as Karpas 909, a human
      myeloma cell line, directly produce DcR3. By interacting with FasL, this molecule
      could inhibit OC apoptosis. In fact, the use of a neutralizing anti-DcR3 antibody
      induces a reduction of cell viability with a consequent increase of apoptotic
      cell number, the activation of caspase-8 and -3, and DNA fragmentation.
      Furthermore, we show that DcR3 supports OC formation in samples from MM patients
      through the upregulation of RANKL and TNFalpha by T lymphocytes and only TNFalpha
      by CD14+ cells. In conclusion, our data provide the first evidence of the
      expression of DcR3 in MM, and the involvement of this molecule in supporting the
      survival and formation of OCs from MM bone disease patients. The production of
      DcR3 by T lymphocytes confers these cells a role in the pathogenesis of bone
      disease associated with MM.

PMID- 19587707
TI  - Array-based DNA methylation profiling in follicular lymphoma.
AB  - Quantitative methylation profiling was performed using the Illumina GoldenGate
      Assay in untreated follicular lymphoma (FL) (164), paired pre- and post
      transformation FL (20), benign haematopoietic (24) samples and purified B and T
      cells from two FL cases. Methylation values allowed separation of untreated FL
      samples from controls with one exception, based primarily on tumour-specific
      gains of methylation typically occurring within CpG islands. Genes that are
      targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2
      were significantly over-represented among hypermethylated genes. Methylation
      profiles were conserved in sequential FL and t-FL biopsies, suggesting that
      widespread methylation represents an early event in lymphomagenesis and may not
      contribute substantially to transformation. A significant (P<0.05) correlation
      between FL methylation values and reduced gene expression was shown for up to 28%
      of loci. Methylation changes occurred predominantly in B cells with variability
      in the amount of non-malignant tissue between samples preventing conclusive
      correlation with survival. This represents an important caveat in attributing
      prognostic relevance to methylation and future studies in cancer will optimally
      require purified tumour populations to address the impact of methylation on
      clinical outcome.

PMID- 19587708
TI  - Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the
      neurological disease progression in MPS IIIB mice.
AB  - The presence of the blood-brain barrier (BBB) presents the most critical
      challenge in therapeutic development for mucopolysaccharidosis (MPS) IIIB, a
      lysosomal storage disease with severe neurological manifestation, because of
      alpha-N-acetylglucosaminidase (NaGlu) deficiency. Earlier, we showed a global
      central nervous system (CNS) transduction in mice by mannitol-facilitated entry
      of intravenous (IV)-delivered recombinant adeno-associated viral serotype 2
      (rAAV2) vector. In this study, we optimized the approach and showed that the
      maximal transduction in the CNS occurred when the rAAV2 vector was IV injected at
      8 min after mannitol administration, and was approximately 10-fold more efficient
      than IV delivery of the vector at 5 or 10 min after mannitol infusion. Using this
      optimal (8 min) regimen, a single IV infusion of rAAV2-CMV-hNaGlu vector is
      therapeutically beneficial for treating the CNS disease of MPS IIIB in adult
      mice, with significantly extended survival, improved behavioral performance, and
      reduction of brain lysosomal storage pathology. The therapeutic benefit
      correlated with maximal delivery to the CNS, but not peripheral tissues. This
      milestone data shows the first effective gene delivery across the BBB to treat
      CNS disease. The critical timing of vector delivery and mannitol infusion
      highlights the important contribution of this pretreatment to successful
      intervention, and the long history of safe use of mannitol in patients bodes well
      for its application in CNS gene therapy.

PMID- 19587709
TI  - Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as
      a novel therapeutic agent for human pancreatic cancer.
AB  - Survival after pancreatic cancer remains poor despite incremental advances in
      surgical and adjuvant therapy, and new strategies for treatment are needed.
      Oncolytic virotherapy is an attractive approach for cancer treatment. In this
      study, we have evaluated the effectiveness of the Lister vaccine strain of
      vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a
      novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of
      vaccinia virus was effective against all human pancreatic carcinoma cells tested
      in vitro, especially those insensitive to oncolytic adenovirus. The virus
      displayed inherently high selectivity for cancer cells, sparing normal cells both
      in vitro and in vivo, with effective infection of tumors after both intravenous
      (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin
      angiostatin fusion protein was confirmed in a pancreatic cancer model both in
      vitro and in vivo, with evidence of inhibition of angiogenesis. This novel
      vaccinia virus showed significant antitumor potency in vivo against the Suit-2
      model by i.t. administration. This study suggests that the novel Lister strain of
      vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential
      therapeutic agent for pancreatic cancer.

PMID- 19587715
TI  - Adieu to nuclear recycling.

PMID- 19587714
TI  - Japan's tipping point.

PMID- 19587716
TI  - How to stop blogging.

PMID- 19587710
TI  - Engineering ligand-responsive gene-control elements: lessons learned from natural
      riboswitches.
AB  - In the last two decades, remarkable advances have been made in the development of
      technologies used to engineer new aptamers and ribozymes. This has encouraged
      interest among researchers who seek to create new types of gene-control systems
      that can be made to respond specifically to small-molecule signals. Validation of
      the fact that RNA molecules can exhibit the characteristics needed to serve as
      precision genetic switches has come from the discovery of numerous classes of
      natural ligand-sensing RNAs called riboswitches. Although a great deal of
      progress has been made toward engineering useful designer riboswitches,
      considerable advances are needed before the performance characteristics of these
      RNAs match those of protein systems that have been co-opted to regulate gene
      expression. In this review, we will evaluate the potential for engineered RNAs to
      regulate gene expression and lay out possible paths to designer riboswitches
      based on currently available technologies. Furthermore, we will discuss some
      technical advances that would empower RNA engineers who seek to make routine the
      production of designer riboswitches that can function in eukaryotes.

PMID- 19587723
TI  - Journal club. A bioengineer gets schooled by Escherichia coli.

PMID- 19587728
TI  - Flu jabs urged for developing countries.

PMID- 19587729
TI  - US stem-cell research expands.

PMID- 19587731
TI  - Developing nations tackle climate.

PMID- 19587730
TI  - Czech researchers angry over government changes.

PMID- 19587732
TI  - Iran presidential candidate speaks out. Interview by Declan Butler.

PMID- 19587733
TI  - When Earth greened over.

PMID- 19587734
TI  - US AIDS chief lays out priorities.

PMID- 19587741
TI  - Human genetics: One gene, twenty years.

PMID- 19587743
TI  - Route for political interests to weaken conservation.

PMID- 19587742
TI  - Science education: Reading, writing and nanofabrication.

PMID- 19587745
TI  - Interrogation: has abuse been reduced by psychologists?

PMID- 19587744
TI  - Birds and people both depend on China's wetlands.

PMID- 19587746
TI  - Too small to overlook.

PMID- 19587747
TI  - Darwin's last laugh.

PMID- 19587752
TI  - Evolutionary biology: Microbes exploit groundhog day.

PMID- 19587754
TI  - Organic chemistry: Forgotten hydrocarbons prepared.

PMID- 19587753
TI  - Vision: New light on allergy receptor.

PMID- 19587755
TI  - Immunology: B cells break the rules.

PMID- 19587756
TI  - Materials science: Nanotubes sorted using DNA.

PMID- 19587757
TI  - Quantum information: Circuits that process with magic.

PMID- 19587758
TI  - Obituary: Herbert Frank York (1921-2009).

PMID- 19587759
TI  - The possibility of impossible cultures.

PMID- 19587760
TI  - Synthesis at the molecular frontier.

PMID- 19587761
TI  - Biomarkers in psychiatry.

PMID- 19587762
TI  - Toxicology for the twenty-first century.

PMID- 19587763
TI  - The role of black holes in galaxy formation and evolution.
AB  - Virtually all massive galaxies, including our own, host central black holes
      ranging in mass from millions to billions of solar masses. The growth of these
      black holes releases vast amounts of energy that powers quasars and other weaker
      active galactic nuclei. A tiny fraction of this energy, if absorbed by the host
      galaxy, could halt star formation by heating and ejecting ambient gas. A central
      question in galaxy evolution is the degree to which this process has caused the
      decline of star formation in large elliptical galaxies, which typically have
      little cold gas and few young stars, unlike spiral galaxies.

PMID- 19587765
TI  - Type IIn supernovae at redshift z approximately 2 from archival data.
AB  - Supernovae have been confirmed to redshift z approximately 1.7 (refs 1, 2) for
      type Ia (thermonuclear detonation of a white dwarf) and to z approximately 0.7
      (refs 1, 3-5) for type II (collapse of the core of the star). The subclass type
      IIn (ref. 6) supernovae are luminous core-collapse explosions of massive stars
      and, unlike other types, are very bright in the ultraviolet, which should enable
      them to be found optically at redshifts z approximately 2 and higher. In
      addition, the interaction of the ejecta with circumstellar material creates
      strong, long-lived emission lines that allow spectroscopic confirmation of many
      events of this type at z approximately 2 for 3-5 years after explosion (ref. 14).
      Here we report three spectroscopically confirmed type IIn supernovae, at
      redshifts z = 0.808, 2.013 and 2.357, detected in archival data using a method
      designed to exploit these properties at z approximately 2. Type IIn supernovae
      directly probe the formation of massive stars at high redshift. The number found
      to date is consistent with the expectations of a locally measured stellar initial
      mass function, but not with an evolving initial mass function proposed to explain
      independent observations at low and high redshift.

PMID- 19587766
TI  - Direct observation of correlations between individual photon emission events of a
      microcavity laser.
AB  - Lasers are recognized for coherent light emission, the onset of which is
      reflected in a change in the photon statistics. For many years, attempts have
      been made to directly measure correlations in the individual photon emission
      events of semiconductor lasers. Previously, the temporal decay of these
      correlations below or at the lasing threshold was considerably faster than could
      be measured with the time resolution provided by the Hanbury Brown/Twiss
      measurement set-up used. Here we demonstrate a measurement technique using a
      streak camera that overcomes this limitation and provides a record of the arrival
      times of individual photons. This allows us to investigate the dynamical
      evolution of correlations between the individual photon emission events. We apply
      our studies to micropillar lasers with semiconductor quantum dots as the active
      material, operating in the regime of cavity quantum electrodynamics. For laser
      resonators with a low cavity quality factor, Q, a smooth transition from photon
      bunching to uncorrelated emission with increasing pumping is observed; for high-Q
      resonators, we see a non-monotonic dependence around the threshold where quantum
      light emission can occur. We identify regimes of dynamical anti-bunching of
      photons in agreement with the predictions of a microscopic theory that includes
      semiconductor-specific effects.

PMID- 19587764
TI  - Mechanisms promoting translocations in editing and switching peripheral B cells.
AB  - Variable, diversity and joining gene segment (V(D)J) recombination assembles
      immunoglobulin heavy or light chain (IgH or IgL) variable region exons in
      developing bone marrow B cells, whereas class switch recombination (CSR)
      exchanges IgH constant region exons in peripheral B cells. Both processes use
      directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining
      (NHEJ). Errors in either V(D)J recombination or CSR can initiate chromosomal
      translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc)
      translocations of peripheral B cell lymphomas. Collaboration between these
      processes has also been proposed to initiate translocations. However, the
      occurrence of V(D)J recombination in peripheral B cells is controversial. Here we
      show that activated NHEJ-deficient splenic B cells accumulate V(D)J-recombination
      associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh
      breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently
      joined to form translocations, a phenomenon associated with specific Igh-Igl co
      localization. Igh and c-myc also co-localize in these cells; correspondingly, the
      introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations.
      Our studies show peripheral B cells that attempt secondary V(D)J recombination,
      and determine a role for mechanistic factors in promoting recurrent
      translocations in tumours.

PMID- 19587767
TI  - DNA sequence motifs for structure-specific recognition and separation of carbon
      nanotubes.
AB  - Single-walled carbon nanotubes (SWNTs) are a family of molecules that have the
      same cylindrical shape but different chiralities. Many fundamental studies and
      technological applications of SWNTs require a population of tubes with identical
      chirality that current syntheses cannot provide. The SWNT sorting problem-that
      is, separation of a synthetic mixture of tubes into individual single-chirality
      components-has attracted considerable attention in recent years. Intense efforts
      so far have focused largely on, and resulted in solutions for, a weaker version
      of the sorting problem: metal/semiconductor separation. A systematic and general
      method to purify each and every single-chirality species of the same electronic
      type from the synthetic mixture of SWNTs is highly desirable, but the task has
      proven to be insurmountable to date. Here we report such a method, which allows
      purification of all 12 major single-chirality semiconducting species from a
      synthetic mixture, with sufficient yield for both fundamental studies and
      application development. We have designed an effective search of a DNA library of
      approximately 10(60) in size, and have identified more than 20 short DNA
      sequences, each of which recognizes and enables chromatographic purification of a
      particular nanotube species from the synthetic mixture. Recognition sequences
      exhibit a periodic purine-pyrimidines pattern, which can undergo hydrogen-bonding
      to form a two-dimensional sheet, and fold selectively on nanotubes into a well
      ordered three-dimensional barrel. We propose that the ordered two-dimensional
      sheet and three-dimensional barrel provide the structural basis for the observed
      DNA recognition of SWNTs.

PMID- 19587768
TI  - Late Cretaceous seasonal ocean variability from the Arctic.
AB  - The modern Arctic Ocean is regarded as a barometer of global change and amplifier
      of global warming and therefore records of past Arctic change are critical for
      palaeoclimate reconstruction. Little is known of the state of the Arctic Ocean in
      the greenhouse period of the Late Cretaceous epoch (65-99 million years ago), yet
      records from such times may yield important clues to Arctic Ocean behaviour in
      near-future warmer climates. Here we present a seasonally resolved Cretaceous
      sedimentary record from the Alpha ridge of the Arctic Ocean. This palaeo-sediment
      trap provides new insight into the workings of the Cretaceous marine biological
      carbon pump. Seasonal primary production was dominated by diatom algae but was
      not related to upwelling as was previously hypothesized. Rather, production
      occurred within a stratified water column, involving specially adapted species in
      blooms resembling those of the modern North Pacific subtropical gyre, or those
      indicated for the Mediterranean sapropels. With increased CO(2) levels and
      warming currently driving increased stratification in the global ocean, this
      style of production that is adapted to stratification may become more widespread.
      Our evidence for seasonal diatom production and flux testify to an ice-free
      summer, but thin accumulations of terrigenous sediment within the diatom ooze are
      consistent with the presence of intermittent sea ice in the winter, supporting a
      wide body of evidence for low temperatures in the Late Cretaceous Arctic Ocean,
      rather than recent suggestions of a 15 degrees C mean annual temperature at this
      time.

PMID- 19587770
TI  - Ionic high-pressure form of elemental boron.

PMID- 19587772
TI  - Systematic artifacts in metagenomes from complex microbial communities.
AB  - Metagenomics is providing an unprecedented view of the taxonomic diversity,
      metabolic potential and ecological role of microbial communities in biomes as
      diverse as the mammalian gastrointestinal tract, the marine water column and
      soils. However, we have found a systematic error in metagenomes generated by 454
      based pyrosequencing that leads to an overestimation of gene and taxon abundance;
      between 11% and 35% of sequences in a typical metagenome are artificial
      replicates. Here we document the error in several published and original datasets
      and offer a web-based solution (http://microbiomes.msu.edu/replicates) for
      identifying and removing these artifacts.

PMID- 19587773
TI  - Investigation of archaeal and bacterial diversity in fermented seafood using
      barcoded pyrosequencing.
AB  - Little is known about the archaeal diversity of fermented seafood; most of the
      earlier studies of fermented food have focused on lactic acid bacteria (LAB) in
      the fermentation process. In this study, the archaeal and bacterial diversity in
      seven kinds of fermented seafood were culture-independently examined using
      barcoded pyrosequencing and PCR-denaturing gradient gel electrophoresis (DGGE)
      methods. The multiplex barcoded pyrosequencing was performed in a single run,
      with multiple samples tagged uniquely by multiplex identifiers, using different
      primers for Archaea or Bacteria. Because PCR-DGGE analysis is a conventional
      molecular ecological approach, this analysis was also performed on the same
      samples and the results were compared with the results of the barcoded
      pyrosequencing analysis. A total of 13 372 sequences were retrieved from 15 898
      pyrosequencing reads and were analyzed to evaluate the diversity of the archaeal
      and bacterial populations in seafood. The most predominant types of archaea and
      bacteria identified in the samples included extremely halophilic archaea related
      to the family Halobacteriaceae; various uncultured mesophilic Crenarchaeota,
      including Crenarchaeota Group I.1 (CG I.1a and CG I.1b), Marine Benthic Group B
      (MBG-B), and Miscellaneous Crenarchaeotic Group (MCG); and LAB affiliated with
      genus Lactobacillus and Weissella. Interestingly, numerous uncultured mesophilic
      Crenarchaeota groups were as ubiquitous in the fermented seafood as in
      terrestrial and aquatic niches; the existence of these Crenarchaeota groups has
      not been reported in any fermented food. These results indicate that the archaeal
      populations in the fermented seafood analyzed are diverse and include the
      halophilic and mesophilic groups, and that barcoded pyrosequencing is a promising
      and cost-effective method for analyzing microbial diversity compared with
      conventional approaches.

PMID- 19587774
TI  - Bacterial succession in a glacier foreland of the High Arctic.
AB  - Succession is defined as changes in biological communities over time. It has been
      extensively studied in plant communities, but little is known about bacterial
      succession, in particular in environments such as High Arctic glacier forelands.
      Bacteria carry out key processes in the development of soil, biogeochemical
      cycling and facilitating plant colonization. In this study we sampled two roughly
      parallel chronosequences in the foreland of Midre Loven glacier on Svalbard,
      Norway and tested whether any of several factors were associated with changes in
      the structure of bacterial communities, including time after glacier retreat,
      horizontal variation caused by the distance between chronosequences and vertical
      variation at two soil depths. The structures of soil bacterial communities at
      different locations were compared using terminal restriction fragment length
      polymorphisms of 16S rRNA genes, and the data were analyzed by sequential
      analysis of log-linear statistical models. Although no significant differences in
      community structure were detected between the two chronosequences, statistically
      significant differences between sampling locations in the surface and mineral
      soils could be demonstrated even though glacier forelands are patchy and dynamic
      environments. These findings suggest that bacterial succession occurs in High
      Arctic glacier forelands but may differ in different soil depths.

PMID- 19587775
TI  - Novel organization of aromatic degradation pathway genes in a microbial community
      as revealed by metagenomic analysis.
AB  - Several types of environmental bacteria that can aerobically degrade various
      aromatic compounds have been identified. The catabolic genes in these bacteria
      have generally been found to form operons, which promote efficient and complete
      degradation. However, little is known about the degradation pathways in bacteria
      that are difficult to culture in the laboratory. By functionally screening a
      metagenomic library created from activated sludge, we had earlier identified 91
      fosmid clones carrying genes for extradiol dioxygenase (EDO), a key enzyme in the
      degradation of aromatic compounds. In this study, we analyzed 38 of these fosmids
      for the presence and organization of novel genes for aromatics degradation. Only
      two of the metagenomic clones contained complete degradation pathways similar to
      those found in known aromatic compound-utilizing bacteria. The rest of the clones
      contained only subsets of the pathway genes, with novel gene arrangements. A
      circular 36.7-kb DNA form was assembled from the sequences of clones carrying
      genes belonging to a novel EDO subfamily. This plasmid-like DNA form, designated
      pSKYE1, possessed genes for DNA replication and stable maintenance as well as a
      small set of genes for phenol degradation; the encoded enzymes, phenol
      hydroxylase and EDO, are capable of the detoxification of aromatic compounds.
      This gene set was found in 20 of the 38 analyzed clones, suggesting that this
      'detoxification apparatus' may be widespread in the environment.

PMID- 19587776
TI  - An improved synthesis of haloaceteamidine-based inactivators of protein arginine
      deiminase 4 (PAD4).
AB  - Protein arginine deiminase 4 (PAD4) is an enzyme that hydrolyzes peptidyl
      arginine residues to form citrulline and ammonia. This enzyme has been implicated
      in several disease states, e.g. rheumatoid arthritis, and therefore represents a
      unique target for the development of a novel therapeutic. A solution-phase
      synthesis of Cl-amidine, the most potent PAD4 inactivator described to date, has
      been developed. This synthesis proceeds in 80% yield over 4 steps at a
      significantly (12-fold) lower cost.

PMID- 19587777
TI  - Early management, with a minimal initial hospitalization length, of major self
      inflicted rifle wounds to the face by a single latissimus dorsi free
      musculocutaneous flap: a 10-year experience.
AB  - OBJECTIVE: Severe ballistic injuries to the face create complex, composite
      defects of 2 facial subunits. These injuries have an extremely high economic
      impact for the Medicare system. The surgical goal with these patients is to
      restore basic functions of the face with a rapid morphological improvement. Our
      hypothesis is as follows: Early restoration of facial segments with a single free
      multiple island latissimus dorsi flap without primary bone reconstruction can
      significantly reduce hospitalization time and allow earlier psychiatric therapy
      with good morphological results. SURGICAL METHOD: (1) Large debridement, bony
      stabilization with external fixation, and tracheotomy. (2) Definitive early
      reconstruction of soft tissue with composite free latissimus dorsi-scapular
      musculocutaneous flap. (3) Several refinements will optimize the results. STUDY
      DESIGN: Retrospective case series of lower- and middle-face composite facial
      close-range high-energy gunshot wound patients were evaluated. Age, gender,
      mechanism of injury, anatomic subsites involved, surgical procedures, flaps
      utilized, complications, functional outcomes, time of tracheotomy closure,
      hospitalization duration, and beginning of psychiatric treatment were analyzed.
      RESULTS: Twelve defects were gunshot wounds, 12 free latissimus dorsi flaps, and
      no flap losses. Patients received psychiatric treatment after 22 days (7-29); the
      tracheotomy was removed in 10 patients with normal alimentation in all cases.
      Mean hospitalization duration was 21 days. CONCLUSIONS: Free tissue transfer
      techniques allow early reconstruction of the soft tissue framework of the face
      with a single multiple-island flap. Rapid restitution of facial compartments at a
      soft tissue level can dramatically reduce duration of hospitalization.

PMID- 19587778
TI  - The Schizosaccharomyces pombe checkpoint kinases Chk1 and Cds1 are important for
      cell survival in response to cisplatin.
AB  - BACKGROUND: DNA damage checkpoints insure that the integrity of genomic DNA is
      faithfully maintained throughout the eukaryotic cell cycle. In the presence of
      damaged DNA, checkpoints are triggered to delay cell cycle progression to allow
      for DNA repair. In fission yeast, the kinases Chk1 and Cds1 are major components
      of these DNA damage checkpoint pathways. Both Chk1 and Cds1 are important for
      viability in the presence of several DNA damaging agents. In this study we
      hypothesized that Chk1 and Cds1 play a vital role in fission yeast cells ability
      to survive exposure to the DNA damaging agent cisplatin. Cisplatin is a potent
      chemotherapeutic drug that interacts with DNA and causes both inter- and intra
      strand DNA cross-links. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrated
      that treatment with cisplatin in fission yeast causes a Chk1-dependent DNA damage
      signal. chk1(-) cells were sensitive to cisplatin and Chk1 was phosphorylated in
      response to cisplatin treatment. We also showed that a Chk1-dependent DNA damage
      checkpoint pathway is activated in a dose-dependent fashion in cells challenged
      with cisplatin. Furthermore the Cds1 checkpoint kinase was also important for
      viability in cisplatin challenged cells. In cds1(-) cells, cisplatin treatment
      reduced cell viability and this phenotype was exacerbated in a chk1(-)/cds1(-)
      background. CONCLUSIONS/SIGNIFICANCE: Thus, we conclude that the concerted effort
      of both major checkpoint kinases in fission yeast, Chk1 and Cds1, protect cells
      from cisplatin induced DNA damage. These observations are significant because
      they suggest that various classes of inter-strand crosslinking agents may
      generate slightly different lesions as work by others did not observe loss of
      viability in cds1(-) cells treated with other crosslinking agents like nitrogen
      mustard.

PMID- 19587780
TI  - Rubber hand illusion under delayed visual feedback.
AB  - BACKGROUND: Rubber hand illusion (RHI) is a subject's illusion of the self
      ownership of a rubber hand that was touched synchronously with their own hand.
      Although previous studies have confirmed that this illusion disappears when the
      rubber hand was touched asynchronously with the subject's hand, the minimum
      temporal discrepancy of these two events for attenuation of RHI has not been
      examined. METHODOLOGY/PRINCIPAL FINDINGS: In this study, various temporal
      discrepancies between visual and tactile stimulations were introduced by using a
      visual feedback delay experimental setup, and RHI effects in each temporal
      discrepancy condition were systematically tested. The results showed that
      subjects felt significantly greater RHI effects with temporal discrepancies of
      less than 300 ms compared with longer temporal discrepancies. The RHI effects on
      reaching performance (proprioceptive drift) showed similar conditional
      differences. CONCLUSIONS/SIGNIFICANCE: Our results first demonstrated that a
      temporal discrepancy of less than 300 ms between visual stimulation of the rubber
      hand and tactile stimulation to the subject's own hand is preferable to induce
      strong sensation of RHI. We suggest that the time window of less than 300 ms is
      critical for multi-sensory integration processes constituting the self-body
      image.

PMID- 19587779
TI  - Search for an association between V249I and T280M CX3CR1 genetic polymorphisms,
      endothelial injury and preeclampsia: the ECLAXIR study.
AB  - BACKGROUND: Preeclampsia and coronary-artery disease share risk factors,
      suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte
      migration and adhesion and has been implicated in the pathophysiology of several
      inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an
      atheroprotective effect and reduced endothelial dysfunction. The aim of this
      study was to search for an association between V249I and T280M polymorphisms of
      CX3CR1, preeclampsia and endothelial dysfunction. METHODOLOGY/PRINCIPAL FINDINGS:
      We explored these polymorphisms with real-time polymerase chain reaction in a
      case-control study (184 white women with preeclampsia and 184 matched
      normotensive pregnant women). Endothelial dysfunction biomarkers including von
      Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of
      CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and
      M280 alleles were associated neither with preeclampsia, nor with its more severe
      form or with endothelial injury. In contrast, we found a trend toward increased
      CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia
      as compared to its level in later-onset- preeclampsia. CONCLUSIONS/SIGNIFICANCE:
      This is the first study to characterize the CX3CR1 gene polymorphisms in patients
      with preeclampsia. We found no differences in genotype or haplotype frequencies
      between patients with PE and normal pregnancies, suggesting that maternal CX3CR1
      V249I and T280M polymorphisms do not increase susceptibility to preeclampsia.
      Further studies should be performed to directly evaluate the pathophysiological
      role of CX3CL1, a molecule abundantly expressed in endometrium, which has been
      shown to stimulate human trophoblast migration.

PMID- 19587782
TI  - Oocyte-specific deletion of Pten in mice reveals a stage-specific function of
      PTEN/PI3K signaling in oocytes in controlling follicular activation.
AB  - Immature ovarian primordial follicles are essential for maintenance of the
      reproductive lifespan of female mammals. Recently, it was found that
      overactivation of the phosphatidylinositol 3-kinase (PI3K) signaling in oocytes
      of primordial follicles by an oocyte-specific deletion of Pten (phosphatase and
      tensin homolog deleted on chromosome ten), the gene encoding PI3K negative
      regulator PTEN, results in premature activation of the entire pool of primordial
      follicles, indicating that activation of the PI3K pathway in oocytes is important
      for control of follicular activation. To investigate whether PI3K signaling in
      oocytes of primary and further developed follicles also plays a role at later
      stages in follicular development and ovulation, we conditionally deleted the Pten
      gene from oocytes of primary and further developed follicles by using transgenic
      mice expressing zona pellucida 3 (Zp3) promoter-mediated Cre recombinase. Our
      results show that Pten was efficiently deleted from oocytes of primary and
      further developed follicles, as indicated by the elevated phosphorylation of the
      major PI3K downstream component Akt. However, follicular development was not
      altered and oocyte maturation was also normal, which led to normal fertility with
      unaltered litter size in the mutant mice. Our data indicate that properly
      controlled PTEN/PI3K-Akt signaling in oocytes is essential for control of the
      development of primordial follicles whereas overactivation of PI3K signaling in
      oocytes does not appear to affect the development of growing follicles. This
      suggests that there is a stage-specific function of PTEN/PI3K signaling in mouse
      oocytes that controls follicular activation.

PMID- 19587781
TI  - A novel tandem reporter quantifies RNA polymerase II termination in mammalian
      cells.
AB  - BACKGROUND: Making the correct choice between transcription elongation and
      transcription termination is essential to the function of RNA polymerase II, and
      fundamental to gene expression. This choice can be influenced by factors
      modifying the transcription complex, factors modifying chromatin, or signals
      mediated by the template or transcript. To aid in the study of transcription
      elongation and termination we have developed a transcription elongation reporter
      system that consists of tandem luciferase reporters flanking a test sequence of
      interest. The ratio of expression from the reporters provides a measure of the
      relative rates of successful elongation through the intervening sequence.
      METHODOLOGY/PRINCIPAL FINDINGS: Size matched fragments containing the
      polyadenylation signal of the human beta-actin gene (ACTB) and the human beta
      globin gene (HBB) were evaluated for transcription termination using this new
      ratiometric tandem reporter assay. Constructs bearing just 200 base pairs on
      either side of the consensus poly(A) addition site terminated 98% and 86% of
      transcription for ACTB and HBB sequences, respectively. The nearly 10-fold
      difference in read-through transcription between the two short poly(A) regions
      was eclipsed when additional downstream poly(A) sequence was included for each
      gene. Both poly(A) regions proved very effective at termination when 1100 base
      pairs were included, stopping 99.6% of transcription. To determine if part of the
      increased termination was simply due to the increased template length, we
      inserted several kilobases of heterologous coding sequence downstream of each
      poly(A) region test fragment. Unexpectedly, the additional length reduced the
      effectiveness of termination of HBB sequences 2-fold and of ACTB sequences 3- to
      5-fold. CONCLUSIONS/SIGNIFICANCE: The tandem construct provides a sensitive
      measure of transcription termination in human cells. Decreased Xrn2 or Senataxin
      levels produced only a modest release from termination. Our data support overlap
      in allosteric and torpedo mechanisms of transcription termination and suggest
      that efficient termination is ensured by redundancy.

PMID- 19587785
TI  - Improvement of sciatic nerve regeneration using laminin-binding human NGF-beta.
AB  - BACKGROUND: Sciatic nerve injuries often cause partial or total loss of motor,
      sensory and autonomic functions due to the axon discontinuity, degeneration, and
      eventual death which finally result in substantial functional loss and decreased
      quality of life. Nerve growth factor (NGF) plays a critical role in peripheral
      nerve regeneration. However, the lack of efficient NGF delivery approach limits
      its clinical applications. We reported here by fusing with the N-terminal domain
      of agrin (NtA), NGF-beta could target to nerve cells and improve nerve
      regeneration. METHODS: Laminin-binding assay and sustained release assay of NGF
      beta fused with NtA (LBD-NGF) from laminin in vitro were carried out. The
      bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat
      sciatic nerve crush injury model, the nerve repair and functional restoration by
      utilizing LBD-NGF were tested. FINDINGS: LBD-NGF could specifically bind to
      laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic
      nerve crush injury model, we found that LBD-NGF could be retained and
      concentrated at the nerve injury sites to promote nerve repair and enhance
      functional restoration following nerve damages. CONCLUSION: Fused with NtA, NGF
      beta could bind to laminin specifically. Since laminin is the major component of
      nerve extracellular matrix, laminin binding NGF could target to nerve cells and
      improve the repair of peripheral nerve injuries.

PMID- 19587783
TI  - Molecular mechanisms of HIF-1alpha modulation induced by oxygen tension and BMP2
      in glioblastoma derived cells.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is one of most common and still poorly
      treated primary brain tumors. In search for new therapeutic approaches, Bone
      Morphogenetic Proteins (BMPs) induce astroglial commitment in GBM-derived cells
      in vitro. However, we recently suggested that hypoxia, which is characteristic of
      the brain niche where GBM reside, strongly counter-acts BMP effects. It seems
      apparent that a more complete understanding of the biology of GBM cells is
      needed, in particular considering the role played by hypoxia as a signaling
      pathways regulator. HIF-1alpha is controlled at the transcriptional and
      translational level by mTOR and, alike BMP, also mTOR pathway modulates glial
      differentiation in central nervous system (CNS) stem cells. METHODOLOGY/PRINCIPAL
      FINDINGS: Here, we investigate the role of mTOR signaling in the regulation of
      HIF-1alpha stability in primary GBM-derived cells maintained under hypoxia (2%
      oxygen). We found that GBM cells, when acutely exposed to high oxygen tension,
      undergo Akt/mTOR pathway activation and that BMP2 acts in an analogous way.
      Importantly, repression of Akt/mTOR signaling is maintained by HIF-1alpha through
      REDD1 upregulation. On the other hand, BMP2 counter-acts HIF-1alpha stability by
      modulating intracellular succinate and by controlling proline hydroxylase 2
      (PHD2) protein through inhibition of FKBP38, a PHD2 protein regulator.
      CONCLUSIONS/SIGNIFICANCE: In this study we elucidate the molecular mechanisms by
      which two pro-differentiating stimuli, BMP2 and acute high oxygen exposure,
      control HIF-1alpha stability. We previously reported that both these stimuli, by
      inducing astroglial differentiation, affect GBM cells growth. We also found
      differences in high oxygen and BMP2 sensitivity between GBM cells and normal
      cells that should be further investigated to better define tumor cell biology.

PMID- 19587784
TI  - Reduced viability, fertility and fecundity in mice lacking the cajal body marker
      protein, coilin.
AB  - BACKGROUND: Coilin is the signature protein of the Cajal body, a conserved
      nuclear organelle involved in multiple aspects of small ribonucleoprotein (RNP)
      biogenesis. Coilin is required for Cajal body homeostasis in both plants and
      animals. Mice lacking coilin are viable when the mutation is crossed to an
      outbred strain but only partially viable when crossed to inbred lines.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to clarify this issue, we backcrossed
      the coilin deletion onto the C57BL6/J background for ten generations and then
      investigated the consequences of coilin removal on overall viability and
      reproductive success. We conclude that semi-lethal phenotype observed in mixed
      background crosses is due to loss of the Coilin gene (or a very tightly-linked
      locus). Interestingly, coilin knockout embryos die relatively late in gestation,
      between E13.5 and birth. We show that the maternal contribution of coilin is not
      important for organismal viability. Importantly, coilin knockout mice display
      significant fertility and fecundity defects. Mutant males that escape the
      embryonic lethality display reduced testis size, however, both males and females
      contribute to the observed reduction in reproductive fitness.
      CONCLUSIONS/SIGNIFICANCE: The evolutionary conservation of coilin from plants to
      animals suggests that the protein plays an important role, perhaps coordinating
      the activities of various RNA-processing machineries. Our observations are
      consistent with the idea that coilin functions to ensure robust organismal
      development, especially during periods of rapid growth.

PMID- 19587786
TI  - Targeted resequencing and analysis of the Diamond-Blackfan anemia disease locus
      RPS19.
AB  - BACKGROUND: The Ribosomal protein S19 gene locus (RPS19) has been linked to two
      kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient
      Erythroblastopenia in Childhood (TEC). Mutations in RPS19 coding sequences have
      been found in 25% of DBA patients, but not in TEC patients. It has been suggested
      that non-coding RPS19 sequence variants contribute to the considerable clinical
      variability in red cell aplasia. We therefore aimed at identifying non-coding
      variations associated with DBA or TEC phenotypes. METHODOLOGY/PRINCIPAL FINDINGS:
      We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89
      DBA and TEC patients for resequencing. We provide here a catalog of the
      considerable, previously unrecognized degree of variation in this region. We
      identified 73 variations (65 SNPs, 8 indels) that all are located outside of the
      RPS19 open reading frame, and of which 67.1% are classified as novel. We
      hypothesize that specific alleles in non-coding regions of RPS19 could alter the
      binding of regulatory proteins or transcription factors. Therefore, we carried
      out an extensive analysis to identify transcription factor binding sites (TFBS).
      A series of putative interaction sites coincide with detected variants. Sixteen
      of the corresponding transcription factors are of particular interest, as they
      are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or
      leukemia (e.g. GATA-1/2, PU.1, MZF-1). CONCLUSIONS: Specific alleles at predicted
      TFBSs may alter the expression of RPS19, modify an important interaction between
      transcription factors with overlapping TFBS or remove an important stimulus for
      hematopoiesis. We suggest that the detected interactions are of importance for
      hematopoiesis and could provide new insights into individual response to
      treatment.

PMID- 19587787
TI  - Regulation of the Drosophila Enhancer of split and invected-engrailed gene
      complexes by sister chromatid cohesion proteins.
AB  - The cohesin protein complex was first recognized for holding sister chromatids
      together and ensuring proper chromosome segregation. Cohesin also regulates gene
      expression, but the mechanisms are unknown. Cohesin associates preferentially
      with active genes, and is generally absent from regions in which histone H3 is
      methylated by the Enhancer of zeste [E(z)] Polycomb group silencing protein. Here
      we show that transcription is hypersensitive to cohesin levels in two exceptional
      cases where cohesin and the E(z)-mediated histone methylation simultaneously coat
      the entire Enhancer of split and invected-engrailed gene complexes in cells
      derived from Drosophila central nervous system. These gene complexes are modestly
      transcribed, and produce seven of the twelve transcripts that increase the most
      with cohesin knockdown genome-wide. Cohesin mutations alter eye development in
      the same manner as increased Enhancer of split activity, suggesting that similar
      regulation occurs in vivo. We propose that cohesin helps restrain transcription
      of these gene complexes, and that deregulation of similarly cohesin
      hypersensitive genes may underlie developmental deficits in Cornelia de Lange
      syndrome.

PMID- 19587788
TI  - Lack of IL-6 during coxsackievirus infection heightens the early immune response
      resulting in increased severity of chronic autoimmune myocarditis.
AB  - BACKGROUND: Chronic myocarditis is often initiated by viral infection, the most
      common of which is coxsackievirus infection. The precise mechanism by which viral
      infection leads to chronic autoimmune pathology is poorly understood, however it
      is clear that the early immune response plays a critical role. Previous results
      have shown that the inflammatory cytokine interleukin (IL)-6 is integral to the
      development of experimental-induced autoimmune myocarditis. However, the function
      of IL-6 during viral-mediated autoimmunity has yet to be elucidated. METHODS AND
      RESULTS: To address the requirement of IL-6 during disease induction, IL-6
      deficient mice were infected with coxsackievirus B3 (CB3). Following infection,
      mice lacking IL-6 developed increased chronic autoimmune disease pathology
      compared to wild type controls without a corresponding change in the level of
      viral replication in the heart. This increase in disease severity was accompanied
      by elevated levels of TNF-alpha, MCP-1, IL-10, activated T cells and cardiac
      infiltrating macrophage/monocytes. Injection of recombinant IL-6 early following
      infection in the IL-6 deficient mice was sufficient to lower the serum cytokines
      TNF-alpha and IL-10 as well as the serum chemokines MCP-1, MIP-1beta, RANTES and
      MIG with a corresponding decrease in the chronic disease pathology strongly
      suggests an important regulatory role for IL-6 during the early response.
      CONCLUSIONS: While IL-6 plays a pathogenic role in experimental-induced
      autoimmune disease, its function following viral-induced autoimmunity is not
      reprised. By regulating the early immune response and thereby controlling the
      severity of chronic disease, IL-6 directs the outcome of chronic autoimmune
      myocarditis.

PMID- 19587790
TI  - Quantifying inter- and intra-population niche variability using hierarchical
      bayesian stable isotope mixing models.
AB  - Variability in resource use defines the width of a trophic niche occupied by a
      population. Intra-population variability in resource use may occur across
      hierarchical levels of population structure from individuals to subpopulations.
      Understanding how levels of population organization contribute to population
      niche width is critical to ecology and evolution. Here we describe a hierarchical
      stable isotope mixing model that can simultaneously estimate both the prey
      composition of a consumer diet and the diet variability among individuals and
      across levels of population organization. By explicitly estimating variance
      components for multiple scales, the model can deconstruct the niche width of a
      consumer population into relevant levels of population structure. We apply this
      new approach to stable isotope data from a population of gray wolves from coastal
      British Columbia, and show support for extensive intra-population niche
      variability among individuals, social groups, and geographically isolated
      subpopulations. The analytic method we describe improves mixing models by
      accounting for diet variability, and improves isotope niche width analysis by
      quantitatively assessing the contribution of levels of organization to the niche
      width of a population.

PMID- 19587789
TI  - Biophysical mechanism for ras-nanocluster formation and signaling in plasma
      membrane.
AB  - Ras GTPases are lipid-anchored G proteins, which play a fundamental role in cell
      signaling processes. Electron micrographs of immunogold-labeled Ras have shown
      that membrane-bound Ras molecules segregate into nanocluster domains. Several
      models have been developed in attempts to obtain quantitative descriptions of
      nanocluster formation, but all have relied on assumptions such as a constant,
      expression-level independent ratio of Ras in clusters to Ras monomers
      (cluster/monomer ratio). However, this assumption is inconsistent with the law of
      mass action. Here, we present a biophysical model of Ras clustering based on
      short-range attraction and long-range repulsion between Ras molecules in the
      membrane. To test this model, we performed Monte Carlo simulations and compared
      statistical clustering properties with experimental data. We find that we can
      recover the experimentally-observed clustering across a range of Ras expression
      levels, without assuming a constant cluster/monomer ratio or the existence of
      lipid rafts. In addition, our model makes predictions about the signaling
      properties of Ras nanoclusters in support of the idea that Ras nanoclusters act
      as an analog-digital-analog converter for high fidelity signaling.

PMID- 19587791
TI  - Contemporary parallel diversification, antipredator adaptations and phenotypic
      integration in an aquatic isopod.
AB  - It is increasingly being recognized that predation can be a strong diversifying
      agent promoting ecological divergence. Adaptations against different predatory
      regimes can emerge over short periods of time and include many different traits.
      We studied antipredator adaptations in two ecotypes of an isopod (Asellus
      aquaticus) that have, diverged in parallel in two Swedish lakes over the last two
      decades. We quantified differences in escape speed, morphology and behavior for
      isopods from different ecotypes present in these lakes. Isopods from the source
      habitat (reed) coexist with mainly invertebrate predators. They are more stream
      profiled and have higher escape speeds than isopods in the newly colonized
      stonewort habitat, which has higher density of fish predators. Stonewort isopods
      also show more cautious behaviors and had higher levels of phenotypic integration
      between coloration and morphological traits than the reed isopods. Colonization
      of a novel habitat with a different predation regime has thus strengthened the
      correlations between pigmentation and morphology and weakened escape performance.
      The strong signature of parallelism for these phenotypic traits indicates that
      divergence is likely to be adaptive and is likely to have been driven by
      differences in predatory regimes. Furthermore, our results indicate that physical
      performance, behavior and morphology can change rapidly and in concert as new
      habitats are colonized.

PMID- 19587792
TI  - Involvement of Basal Ganglia network in motor disabilities induced by typical
      antipsychotics.
AB  - BACKGROUND: Clinical treatments with typical antipsychotic drugs (APDs) are
      accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and
      catalepsy. As little is known about electrophysiological substrates of such motor
      disturbances, we investigated the effects of a typical APD, alpha-flupentixol, on
      the motor behavior and the neuronal activity of the whole basal ganglia nuclei in
      the rat. METHODS AND FINDINGS: The motor behavior was examined by the open field
      actimeter and the neuronal activity of basal ganglia nuclei was investigated
      using extracellular single unit recordings on urethane anesthetized rats. We show
      that alpha-flupentixol induced EPS paralleled by a decrease in the firing rate
      and a disorganization of the firing pattern in both substantia nigra pars
      reticulata (SNr) and subthalamic nucleus (STN). Furthermore, alpha-flupentixol
      induced an increase in the firing rate of globus pallidus (GP) neurons. In the
      striatum, we recorded two populations of medium spiny neurons (MSNs) after their
      antidromic identification. At basal level, both striato-pallidal and striato
      nigral MSNs were found to be unaffected by alpha-flupentixol. However, during
      electrical cortico-striatal activation only striato-pallidal, but not striato
      nigral, MSNs were found to be inhibited by alpha-flupentixol. Together, our
      results suggest that the changes in STN and SNr neuronal activity are a
      consequence of increased neuronal activity of globus pallidus (GP). Indeed, after
      selective GP lesion, alpha-flupentixol failed to induce EPS and to alter STN
      neuronal activity. CONCLUSION: Our study reports strong evidence to show that
      hypokinesia and catalepsy induced by alpha-flupentixol are triggered by dramatic
      changes occurring in basal ganglia network. We provide new insight into the key
      role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can
      be considered as a potential target for the treatment of EPS.

PMID- 19587795
TI  - Lost in translation: reflecting on a model to reduce translation and
      interpretation bias.
AB  - AIM: This paper reflects on the language and translation challenges faced and
      interventions used whilst undertaking cross-cultural public health research in
      Nepal using translators. BACKGROUND: The growth in cross-cultural studies and
      international research highlights the use of translators and the associated
      challenges for researchers with regard to cultural and linguistic issues when
      collecting data in one language and analysing and reporting in another. The
      specific challenges when using translators are frequently overlooked in the
      research literature and translators and the interpretation processes omitted from
      the research methodology and/or discussion. METHODS: The experiences and
      challenges for an English-speaking nurse researcher working with a team of
      translators in a cross-cultural study on the sexual and reproductive health (SRH)
      of young people in Nepal, in 2006, is explored in this paper. The paper employs a
      case study approach. THE STUDY: Data were collected over four weeks observing the
      settings, and the SRH knowledge and practices of participants in two villages in
      Kathmandu Valley were identified using a questionnaire, which was administered as
      a structured interview, and from the nurse researcher's field notes. This
      provided information on the translation and interpretation events. Stages in the
      research process where error could occur are identified in the researchers model
      and the interventions taken to minimise these are discussed which clarify
      perspectives and opinions when researching in the field. FINDINGS AND CONCLUSION:
      Reflecting on translation and interpretation challenges during the data
      collection process in a language which the nurse researcher does not speak, can
      help reduce (or avoid) potential mistakes and error. The paper reflects on a
      model of translation processes which emerged during fieldwork which helps
      understand what events happened and what actions were taken to obtain the most
      accurate data. Using a model such as this for cross cultural fieldwork may be
      useful for both novice and established researchers.

PMID- 19587793
TI  - Essential role for Schizosaccharomyces pombe pik1 in septation.
AB  - BACKGROUND: Schizosaccharomyces pombe pik1 encodes a phosphatidylinositol 4
      kinase, reported to bind Cdc4, but not Cdc4(G107S). PRINCIPAL FINDINGS: Gene
      deletion revealed that pik1 is essential. In cells with pik1 deleted, ectopic
      expression of a loss-of-function allele, created by fusion to a temperature
      sensitive dihydrofolate reductase, allowed normal cell proliferation at 25
      degrees C. At 36 degrees C, cells arrested with abnormally thick, misplaced or
      supernumerary septa, indicating a defect late in septation. In addition to being
      Golgi associated, ectopically expressed GFP-tagged Pik1 was observed at the
      medial cell plane late in cytokinesis. New alleles, created by site-directed
      mutagenesis, were expressed ectopically. Lipid kinase and Cdc4-binding activity
      assays were performed. Pik1(D709A) was kinase-dead, but bound Cdc4. Pik1(R838A)
      did not bind Cdc4, but was an active kinase. Genomic integration of these
      substitutions in S. pombe and complementation studies in Saccharomyces cerevisiae
      pik1-101 cells revealed that D709 is essential in both cases while R838 is
      dispensable. In S. pombe, ectopic expression of pik1 was dominantly lethal;
      while, pik1(D709A,R838A) was innocuous, pik1(R838A) was almost innocuous, and
      pik1(D709A) produced partial lethality and septation defects. The pik1 ectopic
      expression lethal phenotype was suppressed in cdc4(G107S). Thus, D709 is
      essential for kinase activity and septation. CONCLUSIONS: Pik1 kinase activity is
      required for septation. The Pik1 R838 residue is required for important protein
      protein interactions, possibly with Cdc4.

PMID- 19587796
TI  - The use of descriptive words and metaphor in patient and carer experience of
      palliative day care: secondary analysis of a qualitative study.
AB  - BACKGROUND: An independent evaluation of changes to the delivery of Palliative
      Day Services was carried out during 2006-2007 using interviews with service
      users. The analysis found that the words and metaphors employed by users of
      services emphasized their emotional response to the changes, and helped to
      explain their depth of feeling about their experiences, warranting further
      investigation. AIM: To conduct a secondary analysis on interview data collected
      for the Day Services Evaluation Study in order to understand how patients and
      their carers use descriptive words and metaphor when talking about their
      experiences of palliative day services. METHODS: Interview transcripts from 40
      patients and 8 carers were subjected to secondary thematic analysis. These were
      read individually and coded where metaphor or descriptive words had been used to
      emphasize the effect of the illness and the experiences of the Day Services.
      FINDINGS: Examples of the metaphorical expressions and words used described the
      service as a 'secure rock in a changing world'; transition was felt as 'sadness',
      a 'betrayal', with feelings that the changes were 'bitter and twisted;' and left
      'a black hole'. Post transition the mood had changed to acceptance 'When life
      throws lemons at you, you make lemonade'. CONCLUSIONS: The metaphors and
      descriptive words used act as what we describe as 'emotional intensifiers' which
      provide a measure of the impact of the effect of illness, the effect of the day
      services on users and carers and the intensity of feeling during the time of
      transition.

PMID- 19587797
TI  - A finite element model of electrode placement during stimulus evoked
      electromyographic monitoring of iliosacral screw insertion.
AB  - Pelvic ring fractures that occur as a result of substantial orthopedic trauma are
      frequently repaired using iliosacral screws to stabilize the fracture. Stimulus
      evoked electromyography, using pulsed current stimuli provided through the drill
      bit cathode, has been advocated to prevent nerve root injury during iliosacral
      screw insertion. Our objective was to examine the effects of anode location,
      drill bit position, and anatomical structure on the nerve monitoring technique. A
      three-dimensional finite element model was constructed from computed tomography
      data to evaluate the effectiveness of five anode locations at four stations of
      drill bit insertion. Results indicate that the anode location should be at the
      midline or on the side contralateral to drill bit insertion. Locating the anode
      at other positions, such that the nerve root is outside of the primary
      electromagnetic field, leads to an attenuated electromyographic response that
      will ultimately lead to the failure of the monitoring technique.

PMID- 19587798
TI  - Comparative antimicrobial activity of granulysin against bacterial biothreat
      agents.
AB  - Granulysin is a cationic protein produced by human T cells and natural killer
      cells that can kill bacterial pathogens through disruption of microbial membrane
      integrity. Herein we demonstrate antimicrobial activity of the granulysin peptide
      derived from the active site against Bacillus anthracis, Yersinia pestis,
      Francisella tularensis, and Burkholderia mallei, and show pathogen-specific
      differences in granulysin peptide effects. The susceptibility of Y. pestis to
      granulysin is temperature dependent, being less susceptible when grown at the
      flea arthropod vector temperature (26 degrees C) than when grown at human body
      temperature. These studies suggest that augmentation of granulysin expression by
      cytotoxic lymphocytes, or therapeutic application of granulysin peptides, could
      constitute important strategies for protection against select agent bacterial
      pathogens. Investigations of the microbial surface molecules that determine
      susceptibility to granulysin may identify important mechanisms that contribute to
      pathogenesis.

PMID- 19587794
TI  - Common genetic variation near the phospholamban gene is associated with cardiac
      repolarisation: meta-analysis of three genome-wide association studies.
AB  - To identify loci affecting the electrocardiographic QT interval, a measure of
      cardiac repolarisation associated with risk of ventricular arrhythmias and sudden
      cardiac death, we conducted a meta-analysis of three genome-wide association
      studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in
      the UK and the DCCT/EDIC cohort from North America. Five loci were significantly
      associated with QT interval at P<1x10(-6). To validate these findings we
      performed an in silico comparison with data from two QT consortia: QTSCD (n =
      15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common
      variants near NOS1AP (P = 1.4x10(-83)) and the phospholamban (PLN) gene (P =
      1.9x10(-29)). The most associated SNP near NOS1AP (rs12143842) explains 0.82%
      variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval
      duration. We found no evidence for interaction between these two SNPs (P = 0.99).
      PLN is a key regulator of cardiac diastolic function and is involved in
      regulating intracellular calcium cycling, it has only recently been identified as
      a susceptibility locus for QT interval. These data offer further mechanistic
      insights into genetic influence on the QT interval which may predispose to life
      threatening arrhythmias and sudden cardiac death.

PMID- 19587799
TI  - Characteristics of the tooth in the initial movement: the influence of the
      restraint site to the periodontal ligament and the alveolar bone.
AB  - It is critical to clarify orthodontic load transfer mechanism from tooth to
      alveolar bone, and to determine the influence of applied orthodontic force on
      tooth behaviour. In this study, two dimensional (2-D) finite element (FE) models
      were constructed to simulate to mechanical behaviour observed during the initial
      movement of periodontal ligament (PDL) deformation, and to evaluate the effects
      of the presence of PDL and various restraint sites on tooth behaviour.A 2-D solid
      FE model of the tooth-PDL-alveolar bone system was constructed and investigated
      into stress distribution pattern and displacement. The first analysis was carried
      out with combinations of FE model with and without PDL. The second analysis was
      compared with three different sites restraint of alveolar bone. By incorporating
      PDL in FE models, excessively large stress values and deformation generated in a
      tooth and alveolar bone were relieved. Since restraint conditions did not affect
      a tooth and PDL, but had an effect on alveolar bone, orthodontic force necessary
      for tooth displacement was transmitted correctly. The results of this study
      revealed that inclusion of PDL in FE models is indispensable to transmit
      orthodontic force appropriately when investigating tooth behaviour for
      orthodontic treatment. Restrained sites affected stress distribution in alveolar
      bone.

PMID- 19587800
TI  - Staphylococcal enterotoxin A induces small clusters of HLA-DR1 on B cells.
AB  - The superantigen SEA causes non-specific hyperactivation of T and B cells at low
      concentrations. Studies of mutants or soluble proteins suggest SEA is bivalent
      for its ligand, MHC class II. However, the interaction between these molecules on
      intact cells is unknown. On primary mouse B cells expressing the MHC class II
      allele HLA-DR1, measurements of Forster Resonance Energy Transfer between HLA-DR1
      molecules on SEA-treated cells indicated specific clustering, not observed in
      untreated or monovalent superantigen treated cells. Tomographic visualization and
      electron microscopy of immunogold-labeled SEA-treated B cells revealed small
      clusters of surface HLA-DR1 (< or = 4 gold labels). These results present direct
      visual evidence of SEA-mediated clustering of MHC class II molecules on treated
      antigen presenting cells, and provide a new structural approach to addressing
      problems of this nature.

PMID- 19587801
TI  - Parenting Stress in CHARGE Syndrome and the Relationship with Child
      Characteristics.
AB  - This study investigates the parental perception of stress related to the
      upbringing of children with CHARGE syndrome and its association with behavioral
      and physical child characteristics. Parents of 22 children completed the Nijmegen
      Parenting Stress Index-Short, Developmental Behavior Checklist, and Dutch
      Vineland Screener 0-12 and reported their child's problems with hearing, vision
      and ability to speak. Parenting stress was high in 59% of the subjects.
      Behavioral problems on the depression, autism, self-absorbed and disruptive
      behavior scales correlated positively with parenting stress. A non-significant
      trend was found, namely higher stress among the parents of non-speaking children.
      No associations were found with other child characteristics, i.e. level of
      adaptive functioning and intellectual disability, auditory and visual problems,
      deafblindness, gender, and age. Raising a child with CHARGE syndrome is
      stressful; professional support is therefore essential for this population. More
      research into other possible influencing characteristics is needed to improve
      family-oriented interventions. Since CHARGE is a rare syndrome, closer
      international collaboration is needed, not only to expand the group of study
      subjects to increase statistical power, but also to harmonize research designs
      and measurement methods to improve the validity, the reliability, and the
      generalization of the findings.

PMID- 19587802
TI  - Cutaneous chronic graft-versus-host disease does not have the abnormal
      endothelial phenotype or vascular rarefaction characteristic of systemic
      sclerosis.
AB  - BACKGROUND: The clinical and histologic appearance of fibrosis in cutaneous
      lesions in chronic graft-versus -host disease (c-GVHD) resembles the appearance
      of fibrosis in scleroderma (SSc). Recent studies identified distinctive
      structural changes in the superficial dermal microvasculature and matrix of SSc
      skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine
      if c-GVHD is a suitable model for SSc. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed skin biopsies of normal controls (n = 24), patients with SSc (n = 30)
      and c-GVHD with dermal fibrosis (n = 133)). Immunostaining was employed to
      identify vessels, vascular smooth muscle, dermal matrix, and cell proliferation.
      C-GVHD and SSc had similar dermal matrix composition and vascular smooth muscle
      pathology, including intimal hyperplasia. SSc, however, differed significantly
      from c-GVHD in three ways. First, there were significantly fewer (p = 0.00001)
      average vessels in SSc biopsies (9.8) when compared with c-GVHD (16.5). Second,
      in SSc, endothelial markers were decreased significantly (19/19 and 12/14 for VE
      cadherin and vWF (p = <0.0001 and <0.05), respectively). In contrast, 0/13 c-GVHD
      biopsies showed loss of staining with canonical endothelial markers. Third, c
      GVHD contained areas of microvascular endothelial proliferation not present in
      the SSc biopsies. CONCLUSIONS/SIGNIFICANCE: The sclerosis associated with c-GVHD
      appears to resemble wound healing. Focal capillary proliferation occurs in early
      c-GVHD. In contrast, loss of canonical endothelial markers and dermal capillaries
      is seen in SSc, but not in c-GVHD. The loss of VE cadherin in SSc, in particular,
      may be related to microvascular rarefaction because VE cadherin is necessary for
      angiogenesis. C-GVHD is a suitable model for studying dermal fibrosis but may not
      be applicable for studying the microvascular alterations characteristic of SSc.

PMID- 19587803
TI  - Effects of Brood Pheromone Modulated Brood Rearing Behaviors on Honey Bee (Apis
      mellifera L.) Colony Growth.
AB  - A hallmark of eusociality is cooperative brood care. In most social insect
      systems brood rearing labor is divided between individuals working in the nest
      tending the queen and larvae, and foragers collecting food outside the nest. To
      place brood rearing division of labor within an evolutionary context, it is
      necessary to understand relationships between individuals in the nest engaged in
      brood care and colony growth in the honey bee. Here we examined responses of the
      queen, queen-worker interactions, and nursing behaviors to an increase in the
      brood rearing stimulus environment using brood pheromone. Colony pairs were
      derived from a single source and were headed by open-mated sister queens, for a
      total of four colony pairs. One colony of a pair was treated with 336 microg of
      brood pheromone, and the other a blank control. Queens in the brood pheromone
      treated colonies laid significantly more eggs, were fed longer, and were less
      idle compared to controls. Workers spent significantly more time cleaning cells
      in pheromone treatments. Increasing the brood rearing stimulus environment with
      the addition of brood pheromone significantly increased the tempo of brood
      rearing behaviors by bees working in the nest resulting in a significantly
      greater amount of brood reared.

PMID- 19587805
TI  - Do hummingbirds see in ultraviolet?
AB  - We present a numerical model to fit the electroretinogram (ERG), a gross evoked
      eye visual potential, that originate in the retina through photons absorption by
      photoreceptors and then involve the contribution form others retinal neurons. We
      use the ERG measured in a hummingbird, to evaluate the most likely retinal
      mechanism - cones visual pigments and oil-droplets - that participate in their
      high dimensional tetra or pentachromatic color hyperspace. The model - a
      nonlinear fit - appears to be a very useful tool to predict the underlying
      contribution visual mechanism for a variety of retinal preparation.

PMID- 19587804
TI  - New target genes for the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) antitumour activity: Perspectives from the insulin receptor.
AB  - The insulin receptor (IR) plays a crucial role in mediating the metabolic and
      proliferative functions triggered by the peptide hormone insulin. There is
      considerable evidence that abnormalities in both IR expression and function may
      account for malignant transformation and tumour progression in some human
      neoplasias, including breast cancer. PPARgamma is a ligand-activated, nuclear
      hormone receptor implicated in many pleiotropic biological functions related to
      cell survival and proliferation. In the last decade, PPARgamma agonists-besides
      their known action and clinical use as insulin sensitizers-have proved to display
      a wide range of antineoplastic effects in cells and tissues expressing PPARgamma,
      leading to intensive preclinical research in oncology. PPARgamma and activators
      affect tumours by different mechanisms, involving cell proliferation and
      differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We
      recently provided evidence that PPARgamma and agonists inhibit IR by non
      canonical, DNA-independent mechanisms affecting IR gene transcription. We
      conclude that IR may be considered a new PPARgamma "target" gene, supporting a
      potential use of PPARgamma agonists as antiproliferative agents in selected
      neoplastic tissues that overexpress the IR.

PMID- 19587806
TI  - Quantitative texture analysis and transesophageal echocardiography to
      characterize the acute myocardial contusion.
AB  - Myocardial contusion (MC) is a common injury following blunt chest trauma without
      any specific symptoms.Several techniques such as electrocardiogram, estimation of
      myocardial band fraction of creatine phosphokinase, chest radiography and the
      scintiscanning missed efficiency to characterize the MC.Another technique based
      on transesophageal echocardiography [TEE] allows to visualize the structures of
      the heart with a good spatial resolution.We postulated that the quantitative
      texture analysis of regional image texture in two- dimensional [2D] TEE
      echocardiograms would be an accurate method to differentiate normal from abnormal
      myocardial wall.This preliminary experimental study demonstrated the feasibility
      of the proposed technique.

PMID- 19587807
TI  - Parametric analysis of orthopedic screws in relation to bone density.
AB  - A global study of geometry and material properties of orthopedic screws was
      performed, considering not only the effect of each single factor (screw pitch,
      number of threads, fillet angle, etc.) but also their interactions with respect
      to bone density.The stress patterns resulting from different screw geometries and
      bone densities were analyzed using finite element techniques, taking into account
      different levels of osseointegration between the screw and the bone. These
      numerical models where validated through experimental pull-out tests, where a
      pull out force of 120 N produced localized failure of the last thread (stresses
      above 0.42 MPa). The results of the numerical simulations were then summarised
      using a multi-factorial parametric analysis. This demonstrated the great
      relevance of the interaction between bone density and screw pitch, showing that
      the optimal screw pitch can vary by more than 25% for different densities (0.35
      g/cm(3) and 0.47 g/cm(3), respectively).The parameters calculated by means of the
      multi-factorial analysis allow the pull out force to be estimated for different
      osseointegration levels, different screw geometries and material properties, and
      for different bone densities. The final objective is to determine the best choice
      of implant for each individual patient.

PMID- 19587808
TI  - The check your cannabis screener: a new online personalized feedback tool.
AB  - This brief report describes the development and first year of use of an Internet
      based screener for Cannabis users. Two versions of the Check Your Cannabis
      screener were compared, one linked to an already established harm reduction
      website for young Cannabis users (as an exercise called "Check how I compare with
      others," on www.WhatsWithWeed.ca) and the other a standalone version
      (www.CheckYourCannabis.net). The What's With Weed version attracted ten times
      more users and had a significantly younger audience as compared to the standalone
      version, underlining the benefits of targeting a website to a specific audience
      and linking to websites with already established reputations. Further work is
      needed to establish any impact on actual Cannabis use from taking the Check Your
      Cannabis screener.

PMID- 19587809
TI  - Classification of event-related potentials associated with response errors in
      actors and observers based on autoregressive modeling.
AB  - Event-Related Potentials (ERPs) provide non-invasive measurements of the
      electrical activity on the scalp related to the processing of stimuli and
      preparation of responses by the brain. In this paper an ERP-signal classification
      method is proposed for discriminating between ERPs of correct and incorrect
      responses of actors and of observers seeing an actor making such responses. The
      classification method targeted signals containing error-related negativity (ERN)
      and error positivity (Pe) components, which are typically associated with error
      processing in the human brain. Feature extraction consisted of Multivariate
      Autoregressive modeling combined with the Simulated Annealing technique. The
      resulting information was subsequently classified by means of an Artificial
      Neural Network (ANN) using back-propagation algorithm under the "leave-one-out
      cross-validation" scenario and the Fuzzy C-Means (FCM) algorithm. The ANN
      consisted of a multi-layer perceptron (MLP). The approach yielded classification
      rates of up to 85%, both for the actors' correct and incorrect responses and the
      corresponding ERPs of the observers. The electrodes needed for such
      classifications were situated mainly at central and frontal areas. Results
      provide indications that the classification of the ERN is achievable.
      Furthermore, the availability of the Pe signals, in addition to the ERN, improves
      the classification, and this is more pronounced for observers' signals. The
      proposed ERP-signal classification method provides a promising tool to study
      error detection and observational-learning mechanisms in performance monitoring
      and joint-action research, in both healthy and patient populations.

PMID- 19587810
TI  - New Application of IEEE 11073 to Home Health Care.
AB  - We propose a new home health care network for the acquisition and transmission of
      data from ordinary home health care appliances based on IEEE11073. In this study,
      we develop a standard protocol for data collection and a simple interface to
      accommodate different monitoring systems that make use of different data
      protocols. The system provides for one-way data transmission, thus saving power
      and conforming to Japanese pharmaceutical law. Our standardized protocol was
      verified during a 1-year field test involving 20 households in Japan. Data
      transmission errors between home health care devices and the home gateway were
      4.21 per a day with our newly developed standard protocol. Over a 1 year period,
      we collected and analyzed data from 241,000 separate sources associated with
      healthy, home-based patients and chronically ill, clinic-based patients, the
      latter through physician intervention. We evaluate some of the possible
      applications for collecting daily health care data and introduce some of our
      findings relating primarily to body weight and blood pressure monitoring for
      elderly subjects in their own homes.

PMID- 19587811
TI  - Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis
      current status.
AB  - Muscle-specific tyrosine-kinase-antibody-positive myasthenia gravis (MuSK-MG) has
      emerged as a distinct entity since 2001. This disease has been reported
      worldwide, but with varying rates among patients with generalized acetylcholine
      receptor-antibody-negative MG. MuSK-MG was detected in approximately 37% of
      generalized acetylcholine receptor antibody-negative MG. MuSK-MG patients were
      predominantly female with more prominent facial and bulbar involvement and more
      frequent crises. Disease onset tended to be earlier. Patients tended to have a
      relatively poor edrophonium response but showed prominent decrement in the
      repetitive nerve stimulation test in the facial muscles. Patients were more
      likely to display poor tolerance of, or a lack of improvement with,
      anticholinesterase agents. Somewhat better response was observed with steroids
      and plasma exchange. Most were managed successfully with aggressive
      immunomodulatory therapies, although a higher proportion of MuSK-MG patients had
      a refractory course when compared with other forms of generalized MG. I present
      here an up-to-date overview on MuSK-MG based on our experience at the University
      of Alabama at Birmingham and the existing literature.

PMID- 19587812
TI  - Neuro-otological aspects of cerebellar stroke syndrome.
AB  - Cerebellar stroke is a common cause of a vascular vestibular syndrome. Although
      vertigo ascribed to cerebellar stroke is usually associated with other
      neurological symptoms or signs, it may mimic acute peripheral vestibulopathy
      (APV), so called pseudo-APV. The most common pseudo-APV is a cerebellar
      infarction in the territory of the medial branch of the posterior inferior
      cerebellar artery (PICA). Recent studies have shown that a normal head impulse
      result can differentiate acute medial PICA infarction from APV. Therefore,
      physicians who evaluate stroke patients should be trained to perform and
      interpret the results of the head impulse test. Cerebellar infarction in the
      territory of the anterior inferior cerebellar artery (AICA) can produce a unique
      stroke syndrome in that it is typically accompanied by unilateral hearing loss,
      which could easily go unnoticed by patients. The low incidence of vertigo
      associated with infarction involving the superior cerebellar artery distribution
      may be a useful way of distinguishing it clinically from PICA or AICA cerebellar
      infarction in patients with acute vertigo and limb ataxia. For the purpose of
      prompt diagnosis and adequate treatment, it is imperative to recognize the
      characteristic patterns of the clinical presentation of each cerebellar stroke
      syndrome. This paper provides a concise review of the key features of cerebellar
      stroke syndromes from the neuro-otology viewpoint.

PMID- 19587813
TI  - Cerebellar Hypoperfusion during Transient Global Amnesia: An MRI and Oculographic
      Study.
AB  - BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by sudden
      anterograde and retrograde amnesia lasting for up to 24 hours. Diffusion-weighted
      magnetic resonance imaging (DWI) in cases of TGA and ischemia demonstrates a high
      frequency of high signal intensities restricted to the hippocampus, and this has
      been proposed as an etiology of TGA. The aims of this study were to characterize
      the DWI and single-photon-emission computed tomography (SPECT) findings during
      the acute and recovered phases of TGA and to correlate the findings with
      oculomotor abnormalities. METHODS: Five consecutive patients with a clinical
      diagnosis of TGA underwent DWI and SPECT of the brain within 24 hours after
      symptom onset and again 3 days later. Eye movements were also recorded using
      three-dimensional video-oculography. RESULTS: In all patients, DWI disclosed
      small punctuate (1-3 mm), high-signal lesions in the lateral portion of the
      hippocampus. The initial SPECT also revealed hypoperfusion in the cerebellar
      vermis, which had recovered by the follow-up examination. Three patients showed
      saccadic hypermetria or impaired smooth pursuit only during the acute phase.
      CONCLUSIONS: Our patients with TGA showed cerebellar vermian hypoperfusion in
      addition to ischemic insults to the lateral hippocampus. The oculomotor
      abnormalities observed in our patients support the occurrence of cerebellar
      dysfunction during the TGA attack.

PMID- 19587814
TI  - Cognitive Impairment in Essential Tremor without Dementia.
AB  - BACKGROUND AND PURPOSE: Several clinical studies have demonstrated that patients
      with essential tremor (ET) may have cognitive deficits; however, there are no
      published data regarding detailed neuropsychological assessments of ET without
      dementia. We therefore conducted a case-control study of cognitive function in
      patients with ET. METHODS: The cohort for this study comprised 34 consecutive
      patients with ET without dementia and 33 age-matched controls, all of who
      completed a dementia-screening questionnaire and underwent a detailed
      neuropsychological investigation. RESULTS: Severe impairments were observed in
      most domains for the ET group compared to the controls, including attention, part
      of language function, verbal memory, and frontal executive functions.
      CONCLUSIONS: Our results support the finding that the subclinical cognitive
      deficits characterized by attention, verbal memory impairments, and executive
      dysfunction are a clinical feature of ET. In addition, our results also support
      the finding that age at examination and educational status are the most important
      risk factors associated with cognitive deficits in patients with ET.

PMID- 19587815
TI  - Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe
      Atrophy, but with White Matter Changes in Alzheimer's Disease.
AB  - BACKGROUND AND PURPOSE: Elevated plasma total homocysteine (tHcy) levels are
      reported to be associated with an increased risk of Alzheimer's disease (AD).
      However, the mechanism by which homocysteine contributes to the pathogenesis of
      AD is as yet unknown. The aim of this study was to elucidate the relationship
      between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on
      brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients.
      METHODS: Seventy-two patients with a clinical diagnosis of probable AD were
      recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and
      MTA on brain MRI were evaluated in all patients. The AD patients were classified
      into two groups: those with no or minimal WMC (69.2+/-8.8 years, mean+/-SD, n=36)
      and those with moderate-to-severe WMC (74.6+/-4.6 years, n=36) on brain MRI.
      RESULTS: In a univariate logistic regression analysis, the risk of moderate-to
      severe WMC in AD was significantly associated with increasing age, female gender,
      lower education level, hypertension, high plasma tHcy levels, and lower Mini
      Mental State Examination (MMSE) score. Multivariate logistic regression analysis
      revealed only high plasma tHcy as the independent and significant risk factor for
      moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education
      level, MMSE score, and hypertension comparing the top tertile - tHcy levels
      >/=12.9 micromol/L - with the bottom tertile - tHcy levels </=9.4
      micromol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84;
      p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99
      1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated
      significantly with either right or left MTA. CONCLUSIONS: Our results suggest
      that the vascular pathway mediates the association between elevated plasma tHcy
      levels and AD.

PMID- 19587816
TI  - Scoliosis in patients with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Scoliosis is more common in patients with Parkinson's
      disease (PD) than in the general elderly population. We compared clinical
      characteristics between PD patients with and without scoliosis, to identify the
      relationship between the direction of scoliosis and the laterality of the
      dominant symptoms of PD. We also studied the associations between dopaminergic
      pharmacotherapy and scoliosis (defined by a spinal curvature deviation of 10
      degrees or larger). METHODS: The study population comprised 97 patients (42 men
      and 55 women) with idiopathic PD. All of the patients submitted to a whole-spine
      scanograph to allow measurement of the degree of scoliosis by Cobb's method.
      RESULTS: True scoliosis was found in 32 of the 97 PD patients, and was observed
      more frequently in women than in men (28 vs. 4, respectively; p=0.006). The age
      of patients without scoliosis was significantly lower than that of those with
      scoliosis (66.5+/-9.2 years vs. 72.8+/-7.3 years, respectively, mean+/-SD,
      p<0.001). There was no correlation between PD symptom laterality and scoliosis.
      The rate of occurrence of scoliosis did not differ between de novo and levodopa
      (L-dopa)-treated patients. CONCLUSIONS: We suggest that neither L-dopa treatment
      nor the laterality of the initial symptoms of PD is related to the appearance of
      scoliosis.

PMID- 19587817
TI  - Acute subdural hematoma following spinal cerebrospinal fluid drainage in a
      patient with freezing of gait.
AB  - BACKGROUND: Headache is a common complication of lumbar puncture (LP). Although
      in most cases post-LP headaches are not severe and have a benign course, they can
      also be a manifestation of a potentially life-threatening complication such as
      subdural hematoma (SDH). CASE REPORT: We describe a patient in whom a massive SDH
      developed after LP and cerebrospinal fluid (CSF) drainage, which were performed
      during the diagnostic evaluation of freezing of gait. CONCLUSIONS: SDH should not
      be excluded from the differential diagnosis of headache following LP, especially
      when there is a loss of CSF.

PMID- 19587818
TI  - Stroke mimicking encephalopathy as an initial manifestation of diffuse large B
      cell lymphoma.
AB  - BACKGROUND: Systemic lymphoma can be difficult to recognize due to its diverse
      manifestations. Paraneoplastic leukoencephalopathy has rarely been reported in
      the context of lymphoma. CASE REPORT: We report a 45-year-old man with systemic
      lymphoma whose initial manifestation was sudden-onset leukoencephalopathy,
      mimicking stroke. This patient, who was eventually diagnosed with diffuse large B
      cell lymphoma, initially presented with sudden cognitive impairment and gait
      disturbance. Radiological studies suggested a paraneoplastic leukoencephalopathy.
      Chemotherapy for lymphoma resulted in clinical and radiological improvement.
      CONCLUSIONS: The presented case indicates that diffuse large B-cell lymphoma may
      initially appear as a treatable leukoencephalopathy.

PMID- 19587819
TI  - Abnormal vestibular evoked myogenic potentials in medial medullary infarction.
AB  - BACKGROUND: The medial vestibulospinal tract (MVST), which descends in the medial
      longitudinal fasciculus (MLF), may mediate the vestibular evoked myogenic
      potentials (VEMPs) in the contracting sternocleidomastoid muscle. We report
      herein abnormal VEMPs in a patient with medial medullary infarction (MMI) that
      appeared to involve the MLF. CASE REPORT: A patient with infarction involving the
      right medial medulla showed decreased p13-n23 amplitude and increased p13/n23
      latencies of the VEMPs on the right side. These abnormal VEMPs recorded in an MMI
      patient support the theory that VEMPs are mediated by the MVST contained within
      the MLF. CONCLUSIONS: VEMPs may represent a valuable tool for investigating
      vestibular dysfunction originating from the saccule, even in patients with
      central vestibulopathies, which is not readily defined by conventional vestibular
      function tests.

PMID- 19587821
TI  - Erratum.
AB  - [This corrects the article on p. 39 in vol. 5, PMID: 19513333.].

PMID- 19587820
TI  - Erratum.
AB  - [This corrects the article on p. 33 in vol. 5, PMID: 19513332.].

PMID- 19587822
TI  - Is chronic inflammation a possible cause of obesity-related depression?
AB  - Adult obesity has been associated with depression, especially in women. Whether
      depression leads to obesity or obesity causes depression is unclear. Chronic
      inflammation is observed in obesity and depression. In 63 obese women without
      additional diseases depression level was assessed with the Beck's questionnaire.
      After evaluation of depression level study group was divided into groups
      according to the mood status (A--without depression, B-mild depression, and C-
      severe depression), and serum concentration of TNF-alpha, sTNFs, leptin, and IL-6
      were measured by ELISA. No differences in age, body mass, BMI, and body
      composition were observed in study groups. We did not observe differences of
      serum concentrations of TNF-alpha, sTNFRs, leptin, and IL-6 between subgroup A
      and subgroups B and C. It seems that circulating adipokines did not exert
      influence on depression levels in obese women.

PMID- 19587823
TI  - Leiomyosarcomas of vascular origin in the extremity.
AB  - Between 1996 and 2006 a total of 278 patients with soft tissue Leiomyosarcoma
      were treated at our centre. We identified 16 patients (5.8%) where the tumour
      directly arose from the blood vessels. These tumours were studied to determine
      their prognosis and behaviour. All tumors were in the lower limbs: 11 from the
      femoral vein, 3 popliteal vein, and 2 from the posterior tibial vein. Mean tumour
      size was 10.4 cm (3 to 33). Histological grade was high in all patients. Surgical
      treatment was amputation in one, excision with or without vascular reconstruction
      in 12 followed by radiotherapy, and 3 patients had no surgery because of advanced
      disease at diagnosis. Seven out of the 16 patients (44%) had metastasis at
      diagnosis, and five patients without metastasis at diagnosis rapidly developed
      metastases at a median time of 5 months from diagnosis (2-30 months). The overall
      survival of the patients at 5 years was 25% which was considerably worse than
      those with nonvascular leiomyosarcoma. We conclude that patients with
      leiomyosarcoma of vascular origin have a very high risk of metastases and poor
      prognosis when treated in the conventional way.

PMID- 19587824
TI  - In Vitro Evaluation of Oxoplatin: An Oral Platinum(IV) Anticancer Agent.
AB  - Platinum(IV) compounds like oxoplatin (cis, cis, trans-diammine-dichlorido
      dihydroxido-platinum(IV)) show increased stability and therefore can be applied
      orally. In a panel of 38 human cancer cell lines this drug induced S-phase arrest
      and cell death with IC(50) values 2.5-fold higher than cisplatin. Oxoplatin may
      be converted to cisplatin by intracellular reducing agents, however, exposure to
      0.1 M HCl mimicking gastric acid yielded cis-diammine-tetrachlorido-platinum(IV)
      exhibiting twofold increased activity. Similar results were obtained for another
      platinum(IV) compound, JM 149 (ammine-dichlorido-(cyclohexylamine)-dihydroxido
      platinum(IV)), but not for its parent drug JM 216/satraplatin. Genome-wide
      expression profiling of H526 small cell lung cancer cells treated with these
      platinum species revealed clear differences in the expression pattern of affected
      genes between oxoplatin and cisplatin. In conclusion, oxoplatin constitutes a
      potent oral agent that is either reduced or converted to distinct active
      compounds, for example, by gastric acid or acidic areas prevailing in solid
      tumors, in dependence of the respective pharmaceutical formulation.

PMID- 19587825
TI  - Intestinal radiation-induced stricture favours small bowel obstruction by
      phytobezoar: report of a case.
AB  - Bezoars represent the fifth most frequent cause of acute small bowel obstruction.
      Phytobezoar is the most common type of bezoar. It is a concretion of undigestible
      fibers derived from ingested vegetables and fruits. We report a case of a woman
      with a 1-year history of recurrent epigastric and periumbilical abdominal pain
      with intermittent vomiting caused by phytobezoar of the terminal ileum. After
      careful investigation of the case and review of literature, we identified the
      factor involved in bezoar formation as radiation-induced ileal stenosis due to
      previous treatment for a pelvic tumour. This report provides evidence to consider
      phytobezoar as a possible cause of small bowel obstruction in patients previously
      treated with abdominal radiotherapy.

PMID- 19587826
TI  - Atrial natriuretic Peptide in young and elderly children with mild
      gastroenteritis.
AB  - OBJECTIVE: Atrial Natriuretic Peptide (ANP) has natriuretic and diuretic effects,
      synthesized and stored in the atrial cells, released in response to stretch of
      the atrial muscle during increase venous return. Acute gastroenteritis (AGE)
      causes dehydration. We intend to determine whether the decrease in venous return
      due to dehydration would lead to a decrease in ANP levels. PATIENTS AND METHODS:
      This is a prospective observational controlled study. Blood collected from 30
      children with AGE and ANP's levels were compared with 25 controls. ANP levels
      were determined by radioimmunoassay. RESULTS: The study group was in mild
      dehydration. As a significant difference was found in ANP levels between children
      in the 3mo-3y group and older children 3y-14y. We analyzed the results according
      to age. No difference was found between children with AGE and control, in the 3mo
      3y, ANP was 12.1 +/- 11 pg/ml versus 13.4 +/- 12 pg/ml respectively, and 3 +/- 2
      versus 3.8 +/- 3 pg/ml in the 3y-14y groups, respectively. CONCLUSION:
      Dehydration due to AGE does not change the ANP's plasma levels. A weak positive
      correlation between sodium levels and ANP was found r = 0.29. The significant
      finding of our study is the difference in ANP levels related to age, in the
      control as well as the GE group.

PMID- 19587828
TI  - Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients
      with zollinger ellison syndrome.
AB  - Objectives. Zollinger-Ellison Syndrome (ZES) results in hypersecretion of gastric
      acid (via gastrinoma) leading to peptic ulcers, diarrhea, and abdominal pain. We
      describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the
      proximal duodenal bulb in patients with ZES, which we hypothesize results in an
      increased incidence of postbulbar ulcers in patients with ZES (a mechanism
      previously unreported). We determined the incidence of the novel finding of
      duodenal gastric oxyntic hypertrophic heterotopia (GOH) in patients with ZES.
      Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was
      established by hypergastrinemia, gastric acid hypersecretion, and a positive
      secretin test or based on biopsy specimens (evaluated via tissue staining). Basal
      acid output (BAO) and baseline gastrin secretion were determined by established
      methods. Endoscopic examinations with methylene blue staining and biopsy of the
      gastric and duodenal mucosa were conducted in all patients every 3-6 months for
      an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH
      in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from
      the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric
      type epithelium with hypertrophic oxyntic glands in the lamina propria in 5
      patients. Two of the patients had no evidence of GOH in the duodenal bulb.
      Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of
      2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions.
      This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7
      patients with ZES and an intact stomach and duodenum. The presence of
      hypertrophic and heterotopic gastric mucosa is proposed to result from increased
      gastrin levels and may contribute to the increased incidence of postbulbar ulcers
      in these patients.

PMID- 19587829
TI  - Estimation of Cachexia among Cancer Patients Based on Four Definitions.
AB  - Objectives. Estimate and compare the proportion of cancer patients with cachexia
      using different definitions from available clinical data. Methods. Electronic
      medical records were examined to estimate the proportion of cancer patients with
      cachexia using 4 definitions: (1) ICD-9 diagnostic code of 799.4 (cachexia), (2)
      ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding
      difficulties, (3) prescription for megestrol acetate, oxandrolone, somatropin, or
      dronabinol, and (4) >/=5% weight loss. Patients with cancer of the stomach,
      pancreas, lung, colon/rectum, head/neck, esophagus, prostate, breast, or liver
      diagnosed between 1999 and 2004 were followed for cachexia. Results. Of 8541
      cancer patients (60% men and 55% Caucasian), cachexia was observed in 2.4% of
      patients using the cachexia diagnostic code, 5.5% expanded diagnoses, 6.4%
      prescription medication definition, and 14.7% with >/=5% weight loss.
      Conclusions. The proportion of patients with cachexia varied considerably
      depending upon the definition employed, indicating that a standard operational
      definition is needed.

PMID- 19587827
TI  - Experimental study of the effects of marrow mesenchymal stem cells transfected
      with hypoxia-inducible factor-1alpha gene.
AB  - OBJECTIVE: To construct the eukaryotic expression vector hypoxia-inducible factor
      1alpha-pcDNA(3.1) and to investigate its transfective efficiency into mesenchymal
      stem cells (MSCs) in vitro and the expression of HIF-1alpha gene in MSCs.
      METHODS: mRNA of Wistar Rats' myocardial cells was extracted, and cDNA was
      synthesized with Reverse Transcription Kit, HIF-1alpha was amplified by
      polymerase chain reaction (PCR), and constructed into pcDNA(3.1). Transfected HIF
      1alpha-pcDNA(3.1) into MSCs by liposome mediated method. The expression of HIF
      1alpha in the cells was detected by Western Blot Analysis and ELISA. RESULTS:
      Eukaryotic expression vector HIF-1alpha-pcDNA(3.1) was constructed successfully.
      Analyzed by flow cytometer, The MSCs' surfaces mark were CD44+, SH3(CD73)+, CD34
      , CD45- and the CD44+ cells and SH3(CD73)+ cells were 94.7% and 97.3%,
      respectively, showing the high purity of the cultured MSCs. After inducing, the
      cultured MSCs can differentiate into osteoblasts and adipocytes successfully. In
      HIF-1alpha gene transfected MSCs, the expression of HIF-1alpha mRNA and HIF
      1alpha protein were both increased obviously. CONCLUSION: HIF-1alpha was cloned
      successfully. HIF-1alpha-pcDNA(3.1) can be transfected into MSCs by liposome
      mediated method effectively and which resulting stable expression of HIF-1alpha
      in transfected MSCs.

PMID- 19587830
TI  - Synthesis and characterization of bis[(2-ethyl-5-methyl-imidazo-4
      yl)methyl]sulfide and its coordination behavior toward Cu(II) as a possible
      approach of a copper site type I.
AB  - The synthesis and characterization of a novel ligand, bis[(2-ethyl-5-methyl
      imidazo-4-yl)methyl]sulfide (bemims), as well as a bemims-containing copper(II)
      coordination complex are described. In this complex, [Cu(bemims)X(2)] with X =
      NO(3) (-), bemims acts as a tridentate ligand and two monodentate nitrate ions
      complete the coordination sphere. Both imidazole N atoms and the thioether S atom
      of bemims participate in coordination. The Cu(II) ion is five-coordinated with a
      slightly distorted square-pyramidal geometry (tau = .09). Electrochemical studies
      and spectroscopic data for this complex are compared with some blue copper
      proteins in order to assess its ability to mimic the copper center of type I
      copper proteins.

PMID- 19587831
TI  - A variation in the cerebroside sulfotransferase gene is linked to exercise
      modified insulin resistance and to type 2 diabetes.
AB  - AIMS: The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is
      present in the secretory granules of the insulin producing beta-cells and may act
      as a molecular chaperone of insulin. The final step in sulfatide synthesis is
      performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this
      study was to investigate whether two single nucleotide polymorphisms (SNP),
      rs2267161 located in an exon or rs42929 located in an intron, in the gene
      encoding CST are linked to type 2 diabetes (T2D). METHODS: As a population
      survey, 265 male and female patients suffering from T2D and 291 gender matched
      controls were examined. RESULTS: A higher proportion of T2D patients were
      heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles
      present (49.8% versus 41.3%, P = .04). The calculated odd risk for T2D was 1.47
      (1.01-2.15, P = .047). Among female controls, the homozygous CC individuals
      displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or
      TT persons; this was particularly prevalent in individuals who exercise (P =
      .03). CONCLUSION: Heterozygosity at SNP rs2267161 in the gene encoding the CST
      enzyme confers increased risk of T2D. Females with the CC allele showed lower
      insulin resistance.

PMID- 19587832
TI  - Case hepatic endometriosis: a continuing diagnostic dilemma.
AB  - BACKGROUND: Intraparenchymal endometriosis of liver is rare. It may present as
      liver tumour and the diagnosis is not usually established till after surgery.
      CASE OUTLINE: A 48-year-old postmenopausal woman presented with right upper
      quadrant pain and a cystic liver mass. Liver function tests and tumour markers
      (alphaFP, CEA, CA 19-9, and CA 125) were normal. Radiological imaging (USS, CT
      and MRI) suggested a thick walled cystic mass involving segments IV and VIII with
      complex intracystic septations. Frozen section at operation suggested a benign
      cystadenoma. The cyst was enucleated using a CUSA (Cavitron ultrasonic
      aspirator). The final histology confirmed endometriosis. DISCUSSION: Eleven cases
      of hepatic endometrioma have been reported and only four in postmenopausal women.
      Preoperative diagnosis poses a challenge and so far none of the cases have been
      diagnosed preoperatively. Surgery remains the treatment of choice. Accurate
      diagnosis at time of operation may avoid extensive liver surgery and its
      associated morbidity.

PMID- 19587833
TI  - Monocyte chemoattractant protein 1 is a prognostic marker in ANCA-associated
      small vessel vasculitis.
AB  - BACKGROUND: The (anti neutrophil cytoplasmatic autoantibody ANCA), associated
      small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders,
      involving various organs, such as the kidneys. (Monocyte chemoattractant protein
      1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and
      recent studies have pointed out MCP-1 as a promising marker of renal
      inflammation. Here we measure urinary cytokine levels in different phases of
      disease, exploring the possible prognostic value of MCP-1, together with
      (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). METHODS:
      MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits,
      whereas IgM in the urine was measured by an in-house ELISA. RESULTS: The MCP-1
      levels in urine were significantly higher in patients in stable phase of the
      disease, compared with healthy controls. Patients in stable phase, with
      subsequent adverse events; had significantly higher MCP-1 values than patients
      who did not. MCP-1 and IgM both tended to be higher in patients relapsing within
      three months, an observation, however, not reaching statistical significance.
      Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated
      with disease outcome. CONCLUSIONS: Patients with ASVV have raised cytokine levels
      in the urine compared to healthy controls, even during remission. Raised MCP-1
      levels are associated with poor prognosis and possibly also with relapse
      tendency. The association with poor prognosis was stronger for U-MCP-1 than for
      conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to
      candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have
      promising potential as a prognostic marker in ASVV.

PMID- 19587834
TI  - The role of sexual self-schema in a diathesis-stress model of sexual dysfunction.
AB  - Sexual self-schemas are cognitive generalizations regarding sexual aspects of the
      self that represent a core component of one's sexuality. We contend that
      individual differences in the sexual self-view represent an important cognitive
      diathesis for predicting sexual difficulty or dysfunction. We illustrate the role
      of sexual self-schemas on sexual behavior and responsiveness in healthy female
      and male samples. Next, we describe how diathesis-stress models of
      psychopathology have been applied to the sexual arena, and discuss the critical
      features of clinically useful diathesis variables. Drawing from these criteria,
      we examine the diathetic properties of sexual self-schemas. Finally, we discuss
      an empirical test of the proposed diathesis-stress interaction, reviewing the
      role of women's sexual self-views on sexual morbidity following diagnosis and
      treatment for gynecologic cancer.

PMID- 19587835
TI  - Electrical microfluidic pressure gauge for elastomer microelectromechanical
      systems.
AB  - We report on an electrical microfluidic pressure gauge. A polydimethylsiloxane
      microvalve closes at a characteristic applied pressure determined by the
      material's properties and the valve's dimensions. Hence, when the same pressure
      is applied to all valves of a heterogeneous valve array, some valves close while
      others remain open. The state of the array is combined with knowledge of the
      respective characteristic closing pressures of the individual valves to yield an
      estimate of the applied pressure. The state of each valve is obtained by
      electrical measurements, since the electrical resistance of the respective
      underlying fluid-filled channel increases by at least two orders of magnitude as
      the valve closes and its insulating elastomer material interrupts the electrical
      circuit. The overall system functions as a pressure gauge with electrical
      readout. This device would be a critical component in active pressure-regulation
      loops in future integrated microfluidic systems.

PMID- 19587836
TI  - A combined molecular dynamics/density-functional theoretical study on the
      structure and electronic properties of hydrating water molecules in the minor
      groove of decameric DNA duplex.
AB  - A combined molecular dynamics/density-functional theoretical study was carried
      out to address the propensity of ambient water to form cross-strand bridging
      water (CSBW) and their effects on the electronic properties of a fully hydrated
      DNA duplex 5'-d(CCATTAATGG)(2)-3'. The simulation shows ubiquitous presence of up
      to five CSBWs along the minor groove, each with residence time ranging from 400
      ps to 750 ps. The molecular orbitals localized on these CSBWs are nearly
      degenerate in energy with the highest occupied molecular orbital of DNA localized
      on guanine bases, strongly indicating that the hole transport along the guanines
      is mediated by the ubiquitous CSBWs.

PMID- 19587837
TI  - Development of a noncontact 3-D fluorescence tomography system for small animal
      in vivo imaging.
AB  - Fluorescence imaging is an important tool for tracking molecular-targeting probes
      in preclinical studies. It offers high sensitivity, but nonetheless low spatial
      resolution compared to other leading imaging methods such CT and MRI. We
      demonstrate our methodological development in small animal in vivo whole-body
      imaging using fluorescence tomography. We have implemented a noncontact fluid
      free fluorescence diffuse optical tomography system that uses a raster-scanned
      continuous-wave diode laser as the light source and an intensified CCD camera as
      the photodetector. The specimen is positioned on a motorized rotation stage.
      Laser scanning, data acquisition, and stage rotation are controlled via LabVIEW
      applications. The forward problem in the heterogeneous medium is based on a
      normalized Born method, and the sensitivity function is determined using a Monte
      Carlo method. The inverse problem (image reconstruction) is performed using a
      regularized iterative algorithm, in which the cost function is defined as a
      weighted sum of the L-2 norms of the solution image, the residual error, and the
      image gradient. The relative weights are adjusted by two independent
      regularization parameters. Our initial tests of this imaging system were
      performed with an imaging phantom that consists of a translucent plastic cylinder
      filled with tissue-simulating liquid and two thin-wall glass tubes containing
      indocyanine green. The reconstruction is compared to the output of a finite
      element method-based software package NIRFAST and has produced promising results.

PMID- 19587838
TI  - Fiber photo-catheters for laser treatment of atrial fibrillation.
AB  - A fiber photo-catheter has been developed for surgical treatment of atrial
      fibrillation with laser radiation. Atrial fibrillation (AF) is a heart rhythm
      abnormality that involves irregular and rapid heartbeats. Recent studies
      demonstrate the superiority of treating AF disease with optical radiation of the
      near infrared region. To produce long continuous transmural lesions, solid-state
      lasers and laser diodes, along with end-emitting fiber catheters, have been used
      experimentally. The absence of side-emitting flexible catheters with the ability
      to produce long continuous lesions limits the further development of this
      technology. In this research, a prototype of an optical catheter, consisting of a
      flexible 10-cm fiber diffuser has been used to make continuous photocoagulation
      lesions for effective maze procedure treatments. The system also includes: a
      flexible optical reflector; a series of openings for rapid self-attachment to the
      tissue; and an optional closed-loop irrigating chamber with circulating saline to
      cool the optical diffuser and irrigate the tissue.

PMID- 19587839
TI  - Competition of hospital-acquired and community-acquired methicillin-resistant
      Staphylococcus aureus strains in hospitals.
AB  - Recently, we [E.M.C. D'Agata, G.F. Webb, M.A. Horn, R.C. Moellering Jr., and S.
      Ruan, Modellingthe invasion of community-acquired methicillin-resistant
      Staphylococcus aureus into the hospital setting, Clin. Infect. Dis. 48 (2009),
      pp. 274-284] proposed a deterministic mathematical model to characterize the
      factors contributing to the replacement of hospital-acquired methicillin
      resistant Staphylococcus aureus(HA-MRSA) with the community-acquired MRSA (CA
      MRSA) and to quantify the effectiveness of interventionsaimed at limiting the
      spread of CA-MRSA in the hospital setting. Numerical simulations of the model
      strongly suggest that CA-MRSA will become the dominant MRSA strain in the
      hospital setting. In this companion paper, we provide steady-state analysis and
      more numerical simulations of the model. It is shown that when no colonized or
      infected patients enter the hospital, competitive exclusion of HA-MRSA by CA-MRSA
      will occur with increased severity of CA-MRSA infections resulting in longer
      hospitalizations and a larger in-hospital reservoir of CA-MRSA. Improving
      compliance with hand hygiene and decolonization of CA-MRSA carriers are effective
      control strategies.

PMID- 19587840
TI  - Relationship Risks in Context: A Cumulative Risk Approach to Understanding
      Relationship Satisfaction.
AB  - Risks associated with less satisfying intimate relationships often co-occur
      within individuals, raising questions about approaches that consider only their
      independent impact. Utilizing the cumulative risk model, which acknowledges the
      natural covariation of risk factors, this study examined individuals in intimate
      relationships using the Florida Family Formation Survey (n = 2,876) and a
      replication sample (n = 1,048). Analyses confirmed that not only was relationship
      satisfaction lower among those with more risks, but the cumulative risk score was
      predictive above and beyond the individual risk factors. Furthermore,
      experiencing multiple risks exacerbated the negative associations between
      individual risks and relationship satisfaction, suggesting that the operation of
      a risk factor in a relationship is moderated by the presence or absence of other
      risks.

PMID- 19587841
TI  - Charge Transfer Through Single- and Double-strand DNAs: Simulations Based on
      Molecular Dynamics and Molecular Orbital Methods.
AB  - To elucidate the difference in charge transfer through single- and double-strand
      DNAs, we performed simulations based on classical molecular dynamics (MD) and
      semiempirical molecular orbital (MO) methods. Stable structures of DNA strands in
      water were determined by MD simulations and their energy levels and distributions
      of frontier MOs that mediate charge transfer were analyzed by the MO
      calculations. The transfer integrals for a hole or an electron between the
      neighboring DNA bases were estimated from the energy levels of frontier MOs. We
      obtained the current-voltage characteristics for single- and double-strand DNAs
      that are qualitatively in agreement with the experimental results.

PMID- 19587842
TI  - Anti-CD40 agonist antibodies: preclinical and clinical experience.
AB  - The cell-surface molecule CD40, a member of the tumor necrosis factor receptor
      superfamily, broadly regulates immune activation and mediates tumor apoptosis.
      CD40 is expressed by antigen-presenting cells (APC) and engagement of its natural
      ligand on T cells activates APC including dendritic cells and B cells. Agonistic
      CD40 antibodies have been shown to substitute for T cell help provided by CD4+
      lymphocytes in murine models of T cell-mediated immunity. In tumor-bearing hosts,
      CD40 agonists trigger effective immune responses against tumor-associated
      antigens. In contrast, CD40 is also expressed on many tumor cells and its
      ligation in this setting mediates a direct cytotoxic effect. Engagement of CD40
      on tumor cells results in apoptosis in vitro and impaired tumor growth in vivo.
      These observations have prompted efforts to use agonistic CD40 antibodies for the
      treatment of cancer patients and initial clinical results have been promising.

PMID- 19587843
TI  - A novel method for examining response to spelling treatment.
AB  - BACKGROUND: According to a dual-route model of written language processing,
      spelling of irregular words provides an index of the status of lexical spelling
      procedures, whereas nonword spelling provides information about non-lexical
      processing that relies on phoneme-grapheme conversion. Because regular words can
      be spelled using either route, accuracy for such words may reflect the combined
      function of the two routes, and may be mathematically predicted on the basis of
      spelling accuracy for irregular words and nonwords.  AIMS: The purpose of the
      present study was to examine the application of a dual-route prediction equation,
      and a related multiple regression model, to evaluate pre-post treatment spelling
      performance of individuals with acquired alexia/agraphia.  METHODS
      #ENTITYSTARTX00026; PROCEDURES: Eight individuals with language impairment due to
      left hemisphere damage received behavioral treatment to improve their written
      spelling. Their spelling performance was examined before and after treatment on
      untrained word lists with regular and irregular spellings, and pronounceable
      nonwords, and concurrence between predicted and observed spelling of regular
      words was evaluated.  OUTCOMES #ENTITYSTARTX00026; RESULTS: The group
      demonstrated significantly improved spelling performance after treatment, and the
      prediction equation and multiple regression model both accurately predicted
      regular word performance on the basis of irregular word and nonword scores. In
      addition, the multiple regression model provided potentially useful information
      about the relative contribution of the lexical and non-lexical routes to spelling
      performace.  CONCLUSIONS: The prediction equation and related multiple regression
      model used in this study can offer novel insight into the cognitive processes
      available to individuals with agraphia as well as provide a quantitative means to
      characterize response to treatment.

PMID- 19587844
TI  - Designing for dissemination: development of an evidence-based tobacco treatment
      curriculum for psychiatry training programs.
AB  - Psychiatry training programs provide a unique arena for affecting professional
      norms and increasing access to tobacco cessation services among smokers with
      mental illness. Psychiatry Rx for Change emphasizes evidence-based patient
      oriented tobacco treatments relevant for tobacco users with psychiatric
      disorders. Following Diffusion of Innovations theory and the RE-AIM framework,
      the curriculum is being disseminated to psychiatry residency and graduate
      psychiatric nursing programs in the Western United States with plans to study
      curriculum adoption, implementation, and maintenance on a broad scale. Psychiatry
      Rx for Change aims to increase the likelihood that smokers with co-occurring
      disorders will receive evidence-based cessation treatment.

PMID- 19587845
TI  - Predictors of Outpatient Mental Health Service Use by American Youth.
AB  - Among American children and adolescents aged 1 to 17 years, the 12- to 17-year
      olds represent the largest users of outpatient mental health services. This study
      utilizes a nationally representative sample of this age group from the 2005
      National Survey on Drug Use and Health to illuminate predictors of services use
      from three treatment settings: day treatment programs, mental health
      clinics/centers, and private/in-home settings. Univariate analyses were used to
      calculate the percentages of the study sample that used mental health services in
      these settings. In bivariate analyses, the authors estimated the strength of the
      associations between available predisposing, need, and enabling factors and the
      outcomes. Multiple logistic regressions estimated the independent effects of each
      covariate on the outcomes. Lifetime depression, lifetime general anxiety,
      delinquent behaviors, drug dependence, and Medicaid were consistent predictors of
      services use in the three treatment settings. Several other factors were
      associated with services use in bivariate analyses but lost most of their
      statistical significance when the authors adjusted for other confounders.
      Interpreted in light of its potential limitations, this study has important
      research and policy significance.

PMID- 19587846
TI  - Prefrontal activity predicts monkeys' decisions during an auditory category task.
AB  - The neural correlates that relate auditory categorization to aspects of goal
      directed behavior, such as decision-making, are not well understood. Since the
      prefrontal cortex (PFC) plays an important role in executive function and the
      categorization of auditory objects, we hypothesized that neural activity in the
      PFC should predict an animal's behavioral reports (decisions) during a category
      task. To test this hypothesis, we tested PFC activity that was recorded while
      monkeys categorized human spoken words (Russ et al., 2008b). We found that
      activity in the ventrolateral PFC, on average, correlated best with the monkeys'
      choices than with the auditory stimuli. This finding demonstrates a direct link
      between PFC activity and behavioral choices during a non-spatial auditory task.

PMID- 19587847
TI  - Sweet taste signaling functions as a hypothalamic glucose sensor.
AB  - Brain glucosensing is essential for normal body glucose homeostasis and neuronal
      function. However, the exact signaling mechanisms involved in the neuronal
      sensing of extracellular glucose levels remain poorly understood. Of particular
      interest is the identification of candidate membrane molecular sensors that would
      allow neurons to change firing rates independently of intracellular glucose
      metabolism. Here we describe for the first time the expression of the taste
      receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes,
      in the mammalian brain. Neuronal expression of taste genes was detected in
      different nutrient-sensing forebrain regions, including the paraventricular and
      arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the
      hippocampus, the habenula, and cortex. Expression was also observed in the intra
      ventricular epithelial cells of the choroid plexus. These same regions were found
      to express the corresponding gene products that form the heterodimeric T1R2/T1R3
      and T1R1/T1R3 sweet and l-amino acid taste G-protein coupled receptors,
      respectively, along with the taste G-protein alpha-gustducin. Moreover, in vivo
      studies in mice demonstrated that the hypothalamic expression of taste-related
      genes is regulated by the nutritional state of the animal, with food deprivation
      significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus,
      but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low
      glucose medium, while maintaining normal l-amino acid concentrations,
      specifically resulted in higher expression levels of the sweet-associated gene
      Tas1r2. This latter effect was reversed by adding the non-metabolizable
      artificial sweetener sucralose to the low-glucose medium, indicating that taste
      like signaling in hypothalamic neurons does not require intracellular glucose
      oxidation. Taken together, our findings suggest that the heterodimeric G-protein
      coupled sweet receptor T1R2/T1R3 is a candidate membrane-bound brain glucosensor.

PMID- 19587849
TI  - Size and Receptor Density of Glutamatergic Synapses: A Viewpoint from Left-Right
      Asymmetry of CA3-CA1 Connections.
AB  - Synaptic plasticity is considered to be the main mechanism for learning and
      memory. Excitatory synapses in the cerebral cortex and hippocampus undergo
      plastic changes during development and in response to electric stimulation. It is
      widely accepted that this process is mediated by insertion and elimination of
      various glutamate receptors. In a series of recent investigations on left-right
      asymmetry of hippocampal CA3-CA1 synapses, glutamate receptor subunits have been
      found to have distinctive expression patterns that depend on the postsynaptic
      density (PSD) area. Particularly notable are the GluR1 AMPA receptor subunit and
      NR2B NMDA receptor subunit, where receptor density has either a supralinear
      (GluR1 AMPA) or inverse (NR2B NMDAR) relationship to the PSD area. We review
      current understanding of structural and physiological synaptic plasticity and
      propose a scheme to classify receptor subtypes by their expression pattern with
      respect to PSD area.

PMID- 19587850
TI  - Repetitive Transcranial Magnetic Stimulation Affects behavior by Biasing
      Endogenous Cortical Oscillations.
AB  - A governing assumption about repetitive transcranial magnetic stimulation (rTMS)
      has been that it interferes with task-related neuronal activity - in effect, by
      "injecting noise" into the brain - and thereby disrupts behavior. Recent reports
      of rTMS-produced behavioral enhancement, however, call this assumption into
      question. We investigated the neurophysiological effects of rTMS delivered during
      the delay period of a visual working memory task by simultaneously recording
      brain activity with electroencephalography (EEG). Subjects performed visual
      working memory for locations or for shapes, and in half the trials a 10-Hz train
      of rTMS was delivered to the superior parietal lobule (SPL) or a control brain
      area. The wide range of individual differences in the effects of rTMS on task
      accuracy, from improvement to impairment, was predicted by individual differences
      in the effect of rTMS on power in the alpha-band of the EEG ( approximately 10
      Hz): a decrease in alpha-band power corresponded to improved performance, whereas
      an increase in alpha-band power corresponded to the opposite. The EEG effect was
      localized to cortical sources encompassing the frontal eye fields and the
      intraparietal sulcus, and was specific to task (location, but not object memory)
      and to rTMS target (SPL, not control area). Furthermore, for the same task
      condition, rTMS-induced changes in cross-frequency phase synchrony between alpha-
      and gamma-band (>40 Hz) oscillations predicted changes in behavior. These results
      suggest that alpha-band oscillations play an active role cognitive processes and
      do not simply reflect absence of processing. Furthermore, this study shows that
      the complex effects of rTMS on behavior can result from biasing endogenous
      patterns of network-level oscillations.

PMID- 19587848
TI  - Long-term effects of environmental endocrine disruptors on reproductive
      physiology and behavior.
AB  - It is well established that, over the course of development, hormones shape the
      vertebrate brain such that sex specific physiology and behaviors emerge. Much of
      this occurs in discrete developmental windows that span gestation through the
      prenatal period, although it is now becoming clear that at least some of this
      process continues through puberty. Perturbation of this developmental progression
      can permanently alter the capacity for reproductive success. Wildlife studies
      have revealed that exposure to endocrine disrupting compounds (EDCs), either
      naturally occurring or man made, can profoundly alter reproductive physiology and
      ultimately impact entire populations. Laboratory studies in rodents and other
      species have elucidated some of the mechanisms by which this occurs and strongly
      indicate that humans are also vulnerable to disruption. Use of hormonally active
      compounds in human medicine has also unfortunately revealed that the developing
      fetus can be exposed to and affected by endocrine disruptors, and that it might
      take decades for adverse effects to manifest. Research within the field of
      environmental endocrine disruption has also contributed to the general
      understanding of how early life experiences can alter reproductive physiology and
      behavior through non-genomic, epigenetic mechanisms such as DNA methylation and
      histone acetylation. These types of effects have the potential to impact future
      generations if the germ line is affected. This review provides an overview of how
      exposure to EDCs, particularly those that interfere with estrogen action, impacts
      reproductive physiology and behaviors in vertebrates.

PMID- 19587851
TI  - Selective serotonin reuptake inhibitors: a review of its effects on intraocular
      pressure.
AB  - The increase in serotonin (5-HT) neurotransmission is considered to be one of the
      most efficacious medical approach to depression and its related disorders. The
      selective serotonin reuptake inhibitors (SSRIs) represent the most widely
      antidepressive drugs utilized in the medical treatment of depressed patients.
      Currently available SSRIs include fluoxetine, sertraline, paroxetine,
      fluvoxamine, citalopram and escitalopram. The primary SSRIs pharmacological
      action's mechanism consists in the presynaptic inhibition on the serotonin
      reuptake, with an increased availability of this amine into the synaptic cleft.
      Serotonin produces its effects as a consequence of interactions with appropriate
      receptors. Seven distinct families of 5-HT receptors have been identified (5
      HT(1) to 5-HT(7)), and subpopulations have been described for several of these.
      The interaction between serotonin and post-synaptic receptors mediates a wide
      range of functions. The SSRIs have a very favorable safety profile, although
      clinical signs of several unexpected pathologic events are often misdiagnosed, in
      particular, those regarding the eye. In all cases reported in the literature the
      angle-closure glaucoma represents the most important SSRIs-related ocular adverse
      event. Thus, it is not quite hazardous to hypothesize that also the other
      reported and unspecified visual disturbances could be attributed - at least in
      some cases - to IOP modifications. The knowledge of SSRIs individual
      tolerability, angle-closure predisposition and critical IOP could be important
      goals able to avoid further and more dangerous ocular side effects.

PMID- 19587853
TI  - Dopaminergic and noradrenergic contributions to functionality in ADHD: the role
      of methylphenidate.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric
      condition characterized by severe impulsiveness, inattention and overactivity.
      Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the
      noradrenergic systems, is one of the most frequently prescribed treatments for
      ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise
      neurochemical mechanisms of action are under debate. For the most part, MPH's
      influence on subcortical dopamine neurotransmission is thought to play a crucial
      role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH
      action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate
      tonic dopamine while inhibiting phasic transmitter release in subcortical
      structures, leading to reduced postsynaptic receptor stimulation and psychomotor
      activation in response to salient stimuli. Volkow and colleagues [56] suggest
      that by amplifying a weak striatal dopamine signal, MPH increases the perception
      of a stimulus or task as salient. The enhanced interest for the task is thought
      to increase attention and improve performance. Recent animal studies have however
      shown that when administered at doses producing clinically relevant drug plasma
      levels and enhancing cognitive function, MPH preferentially activates dopamine
      and noradrenaline efflux within the prefrontal cortex relative to the subcortical
      structures [5]. Overall, we suggest that the delineated theories of MPH
      therapeutic action should not be discussed as exclusive. Studies are outlined
      that allow integrating the different findings and models.

PMID- 19587854
TI  - Activity-dependent release of adenosine: a critical re-evaluation of mechanism.
AB  - Adenosine is perhaps the most important and universal modulator in the brain. The
      current consensus is that it is primarily produced in the extracellular space
      from the breakdown of previously released ATP. It is also accepted that it can be
      released directly, as adenosine, during pathological events primarily by
      equilibrative transport. Nevertheless, there is a growing realization that
      adenosine can be rapidly released from the nervous system in a manner that is
      dependent upon the activity of neurons. We consider three competing classes of
      mechanism that could explain neuronal activity dependent adenosine release
      (exocytosis of ATP followed by extracellular conversion to adenosine; exocytotic
      release of an unspecified transmitter followed by direct non-exocytotic adenosine
      release from an interposed cell; and direct exocytotic release of adenosine) and
      outline discriminatory experimental tests to decide between them. We review
      several examples of activity dependent adenosine release and explore their
      underlying mechanisms where these are known. We discuss the limits of current
      experimental techniques in definitively discriminating between the competing
      models of release, and identify key areas where technologies need to advance to
      enable definitive discriminatory tests. Nevertheless, within the current limits,
      we conclude that there is evidence for a mechanism that strongly resembles direct
      exocytosis of adenosine underlying at least some examples of neuronal activity
      dependent adenosine release.

PMID- 19587852
TI  - Tianeptine: an antidepressant with memory-protective properties.
AB  - The development of effective pharmacotherapy for major depression is important
      because it is such a widespread and debilitating mental disorder. Here, we have
      reviewed preclinical and clinical studies on tianeptine, an atypical
      antidepressant which ameliorates the adverse effects of stress on brain and
      memory. In animal studies, tianeptine has been shown to prevent stress-induced
      morphological sequelae in the hippocampus and amygdala, as well as to prevent
      stress from impairing synaptic plasticity in the prefrontal cortex and
      hippocampus. Tianeptine also has memory-protective characteristics, as it blocks
      the adverse effects of stress on hippocampus-dependent learning and memory. We
      have further extended the findings on stress, memory and tianeptine here with two
      novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX),
      thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of
      memory in ADX rats is blocked by tianeptine. These findings are consistent with
      previous research which indicates that tianeptine produces anti-stress and memory
      protective properties without altering the response of the hypothalamic-pituitary
      adrenal axis to stress. We conclude with a discussion of findings which indicate
      that tianeptine accomplishes its anti-stress effects by normalizing stress
      induced increases in glutamate in the hippocampus and amygdala. This finding is
      potentially relevant to recent research which indicates that abnormalities in
      glutamatergic neurotransmission are involved in the pathogenesis of depression.
      Ultimately, tianeptine's prevention of depression-induced sequelae in the brain
      is likely to be a primary factor in its effectiveness as a pharmacological
      treatment for depression.

PMID- 19587855
TI  - Triple reuptake inhibitors: the next generation of antidepressants.
AB  - Depression has been associated with impaired neurotransmission of serotonergic,
      norepinephrinergic, and dopaminergic pathways, although most pharmacologic
      treatment strategies for depression enhance only serotonin and norepinephrine
      neurotransmission. Current drug development efforts are aimed at a new class of
      antidepressants which inhibit the reuptake of all three neurotransmitters in the
      hope of creating medications with broader efficacy and/or quicker onset of
      action. The current review explores limitations of presently available
      antidepressants and the history and premise behind the movement to devise triple
      reuptake inhibitors. The evidence for and against the claim that broader spectrum
      agents are more efficacious is discussed. Examples of triple reuptake inhibitors
      in development are compared, and preclinical and clinical research with these
      agents to date is described.

PMID- 19587857
TI  - Neurophysiology of sleep and wakefulness: basic science and clinical
      implications.
AB  - Increased attention to the prevalence of excessive sleepiness has led to a clear
      need to treat this symptom, thus reinforcing the need for a greater understanding
      of the neurobiology of sleep and wakefulness. Although the physiological
      mechanisms of sleep and wakefulness are highly interrelated, recent research
      reveals that there are distinct differences in the active brain processing and
      the specific neurochemical systems involved in the two states. In this review, we
      will examine the specific neuronal pathways, transmitters, and receptors
      composing the ascending arousal system that flow from the brainstem through the
      thalamus, hypothalamus, and basal forebrain to the cerebral cortex. We will also
      discuss the mutually inhibitory interaction between the core neuronal components
      of this arousal system and the sleep-active neurons in the ventrolateral preoptic
      nucleus, which serves as a brainstem-switch, regulating the stability of the
      sleep-wake states. In addition, we will review the role of homeostatic and
      circadian processes in the sleep-wake cycle, including the influence of the
      suprachiasmatic nucleus on coordination of sleep-wake systems. Finally, we will
      summarize how the above processes are reflected in disorders of sleep and
      wakefulness, including insomnia, narcolepsy, disorders associated with fragmented
      sleep, circadian rhythm sleep disorders, and primary neurological disorders such
      as Parkinson's and Alzheimer's diseases.

PMID- 19587858
TI  - Neuropharmacological mechanisms underlying the neuroprotective effects of
      methylphenidate.
AB  - Methylphenidate is a psychostimulant that inhibits the neuronal dopamine
      transporter. In addition, methylphenidate has the intriguing ability to provide
      neuroprotection from the neurotoxic effects of methamphetamine and perhaps also
      Parkinson's disease; both of which may likely involve the abnormal accumulation
      of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation
      of dopamine-associated reactive oxygen species. As delineated in this review, the
      neuroprotective effects of methylphenidate are due, at least in part, to its
      ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation
      through several possible neuropharmacological mechanisms. These may include 1)
      direct interactions between methylphenidate and the neuronal dopamine transporter
      which may attenuate or prevent the entry of methamphetamine into dopaminergic
      neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2
      receptor-mediated signal cascade process, and 2) indirect effects upon the
      functioning of the vesicular monoamine transporter-2 which may increase vesicular
      dopamine sequestration through both vesicle trafficking and the kinetic
      upregulation of the vesicular monoamine transporter-2 protein. Understanding
      these neuropharmacological mechanisms of methylphenidate neuroprotection may
      provide important insights into the physiologic regulation of dopaminergic
      systems as well as the pathophysiology of a variety of disorders involving
      abnormal dopamine disposition ranging from substance abuse to neurodegenerative
      diseases such as Parkinson's disease.

PMID- 19587859
TI  - Prognosis rules in a depressed economy.

PMID- 19587856
TI  - Pharmacology and therapeutic potential of sigma(1) receptor ligands.
AB  - Sigma (sigma) receptors, initially described as a subtype of opioid receptors,
      are now considered unique receptors. Pharmacological studies have distinguished
      two types of sigma receptors, termed sigma(1) and sigma(2). Of these two
      subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its
      amino acid sequence shows no homology with other mammalian proteins. Several
      psychoactive drugs show high to moderate affinity for sigma(1) receptors,
      including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and
      sertraline, and the psychostimulants cocaine and methamphetamine; in addition,
      the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors.
      Certain neurosteroids are known to interact with sigma(1) receptors, and have
      been proposed to be their endogenous ligands. These receptors are located in the
      plasma membrane and in subcellular membranes, particularly in the endoplasmic
      reticulum, where they play a modulatory role in intracellular Ca(2+) signaling.
      Sigma(1) receptors also play a modulatory role in the activity of some ion
      channels and in several neurotransmitter systems, mainly in glutamatergic
      neurotransmission. In accordance with their widespread modulatory role, sigma(1)
      receptor ligands have been proposed to be useful in several therapeutic fields
      such as amnesic and cognitive deficits, depression and anxiety, schizophrenia,
      analgesia, and against some effects of drugs of abuse (such as cocaine and
      methamphetamine). In this review we provide an overview of the present knowledge
      of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the
      role of sigma(1) receptors in behavioral animal studies, which have contributed
      greatly to the potential therapeutic applications of sigma(1) ligands.

PMID- 19587860
TI  - Finite element stress analysis of dental prostheses supported by straight and
      angled implants.
AB  - PURPOSE: A three-dimensional finite element analysis was conducted to evaluate
      and compare the stress distribution around two prosthesis-implant systems, in
      which implants were arranged in either a straight-line or an intrabone offset
      configuration. MATERIALS AND METHODS: The systems were modeled with three
      titanium implants placed in the posterior mandible following a straight line
      along the bone. The straight system was built with three straight implants (no
      offset). The angled system was built as follows: the first implant (mesial) was
      an angled implant inclined lingually, the second (median) was straight, and the
      third (distal) was another angled implant inclined buccally. This buccal incline
      created an intrabone implant offset owing to the inclination of the angled
      implants' bodies. Each system received a metal-ceramic prosthesis with crowns
      that mimicked premolar anatomy. In both systems, an axial load of 100 N and a
      horizontal load of 20 N were applied on the center of the crown of the middle
      implant. RESULTS: In both systems, the major von Mises stresses occurred with
      vertical loading on the mesial and the distal neck area of the first and third
      implants, respectively: 6.304 MPa on the first implant of the straight system and
      6.173 MPa on the third implant in the angled system. The peak stress occurred for
      the minimum principal stress (S3) on the neck of the first implant for both
      systems at the level of -8.835 MPa for the straight system and -8.511 MPa for the
      angled system. There was no stress concentration on the inner or outer angles of
      the angled implants, on the notches along the implant body, or on any apex.
      CONCLUSIONS: In this analysis, the angled system did not induce a stress
      concentration in any point around the implants that was different from that of
      the straight system. The stress distribution was very similar in both systems.

PMID- 19587861
TI  - Comparison of self-tapping and self-drilling orthodontic mini-implants: an animal
      study of insertion torque and displacement under lateral loading.
AB  - PURPOSE: The aim of this study was to compare two types of orthodontic mini
      implants, self-tapping and self-drilling, by measurement of the insertion torques
      and the displacements under lateral loading in an animal model. MATERIALS AND
      METHODS: After predrilling of host sites, 27 self-tapping and 27 self-drilling
      mini-implants were inserted in vitro in the ilia of country pigs. The axial
      drilling forces at each host site and the insertion torques during placement were
      recorded, and the displacements applied by variable lateral force (1 to 9 N) were
      measured. Analyses of covariance with insertion torques or displacements under
      lateral loading as the main effect and average drilling forces as the covariate
      (at the alpha=5% level) were performed to determine statistical significance.
      RESULTS: There was a significant difference in peak insertion torque between the
      self-tapping and self-drilling group (P<.05), except when the average drilling
      force at host sites was less than 1.2 N (P>.05). In addition, this experiment
      demonstrated that the lateral displacement of the self-tapping group was
      comparable to that of the self-drilling group (P>.05). CONCLUSIONS: During
      implantation, the self-tapping implants typically had a lower insertion torque
      than the self-drilling implants. Based on the displacements under lateral
      loading, however, both the self-tapping and self-drilling implants showed similar
      resistance to lateral forces.

PMID- 19587862
TI  - Electrocardiographic alterations during endosseous implant placement performed
      with local anesthetic agents.
AB  - PURPOSE: The purpose of this study was to analyze electrocardiographic
      alterations during dental implant surgeries when local anesthetic agents were
      used. MATERIALS AND METHODS: Twenty implants were placed in 18 healthy patients.
      An electrocardiogram and Wincardio software were used to gather recordings from
      12 static leads every 2 minutes, continuously record coronary artery (D2)
      derivations, and automatically measure the following electrocardiographic
      parameters: heart rate, duration and amplitude of the P wave, PR segment
      duration, ST segment deviation, QRS complex duration, and duration of the RR, QT,
      and corrected QT (QTc) intervals. RESULTS: Analysis of variance of the values
      obtained at the different stages showed significant differences (P<.05) for the
      heart rate and for the duration of the RR and QT intervals. The heart rate
      increased during the anesthesia, incision, and bone drilling stages, reaching a
      peak during drilling. Duration of the RR and QT intervals decreased during the
      incision and drilling stages. Among the electrocardiographic parameters
      individually assessed, several altered values were found for the duration of the
      P wave, the QRS complex, and the QT and QTc intervals. Sinusal tachycardia and
      bradycardia, sinusal arrhythmia, supraventricular extrasystole, ventricular
      extrasystole, and T-wave inversion were detected. CONCLUSION: Dental implant
      placement surgery may induce electrocardiographic alterations. The most
      frequently found arrhythmias were extrasystole and sinusal tachycardia. The
      anesthesia, incision, and bone drilling stages exhibited the highest heart rate
      values and the shortest durations of the RR and QT intervals.

PMID- 19587863
TI  - Effect of titanium surface characteristics on the behavior and function of oral
      fibroblasts.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of different
      titanium surface characteristics on the behavior and function of oral fibroblasts
      as well as the deposition pattern of collagen within the extracellular matrix.
      MATERIALS AND METHODS: Titanium surfaces created by machining, acid etching with
      sulfuric acid (AE1), or acid etching with hydrofluoric acid (AE2) were analyzed
      using scanning electron microscopy (SEM) and energy-dispersive x-ray
      spectroscopy. Rat oral fibroblasts were cultured on different surfaces. Cell
      spread and morphology of extracellular matrix were evaluated using SEM.
      Attachment and proliferation of cells were examined by comparing the numbers of
      attached to detached cells and cell count, respectively. Gene expression was
      analyzed via reverse transcriptase polymerase chain reaction. Collagen production
      and deposition were examined via a Sirius red-based stain assay and confocal
      laser scanning microscopy. RESULTS: The machined surface showed a flat profile
      with isotropic grooves, the AE1 surface showed a uniformly microscale roughened
      surface, and the AE2 surface had a grooved profile with intermediate surface
      roughness. The AE2 surface contained fluoride atoms (2.45%+/-0.44% as F/Ti atomic
      ratio). Cell attachment was significantly weaker on the machined surface than on
      the AE1 and AE2 surfaces, whereas no differences were observed between the AE1
      and AE2 surfaces. The cell counts on the machined and AE2 surfaces were higher,
      with a parallel orientation, whereas the cell count was lower and randomly
      distributed on the AE1 surface. The expression level of fibroblastic genes was
      similar among surfaces for all time points tested. Collagen production was
      highest on the machined surface, followed by AE2 and AE1 surfaces. Collagen
      deposition displayed a parallel pattern on the machined surface, while it was
      multidirectional on the AE1 and AE2 surfaces. CONCLUSION: The surface
      characteristics of titanium affect attachment, spread, and proliferative activity
      of oral fibroblasts as well as the deposition pattern of collagen in vitro.

PMID- 19587864
TI  - Use of biomaterials with or without platelet-rich plasma in postextraction sites:
      a microscopic study in dogs.
AB  - PURPOSE: Sites that will receive dental implants need to be quantitatively and
      qualitatively suitable for this therapy. The treatment of postextraction areas
      with biomaterials associated with platelet-rich plasma (PRP) might make the
      repair process more efficient, resulting in desirable bone characteristics. The
      present study sought to evaluate the effectiveness of PRP in the process of new
      bone formation when associated with biomaterials. MATERIALS AND METHODS: Four
      female dogs were used for this study. Mandibular postextraction sites received
      implants, along with bone substitutes (Bio-Oss [BO] or Biogran [BG]), on the
      right side of the mandible and these biomaterials plus PRP on the left side of
      the mandible. Thirty days later, the tissues were prepared and histologic
      analyses were carried out to compare the repair processes. RESULTS: PRP
      accelerated the repair process for both BO and BG; however, the action of PRP
      associated with BO did not surpass that of BG alone. CONCLUSIONS: The addition of
      PRP appears to accelerate the repair process.

PMID- 19587865
TI  - Nonlinear finite element analysis versus ex vivo strain gauge measurements on
      immediately loaded implants.
AB  - PURPOSE: To evaluate the level of agreement between nonlinear finite element
      stress analysis (NL-FEA) and ex vivo strain gauge analysis (EV-SGA) on
      immediately loaded implants. MATERIALS AND METHODS: Four 4.1-mm-diameter, 12-mm
      long implants were placed bilaterally into the lateral and first premolar regions
      of completely edentulous maxillae of four human cadavers. Two-element 90-degree
      rosette strain gauges were bonded to the labial cortical bone around the
      implants, and 100 N maximal load was applied over two miniature load cells on bar
      retained overdentures while simultaneous data acquisition from load cells and
      strain gauges was performed at a sample rate of 10 KHz. Individualized numeric
      models of the cadavers were constructed, and contact analysis with normal contact
      detection and separation behavior was performed between the implants and bone.
      Upon simulation of the loading regimen, axial and lateral strains were recorded.
      The NL-FEA data and EV-SGA data were compared. RESULTS: There was a high level of
      agreement regarding the quality of strains, as determined by both techniques,
      although the mean values obtained with EV-SGA were higher than those found with
      NL-FEA. However, the strains recorded by NL-FEA did not differ significantly
      (P<.05) from the strains recorded by EV-SGA. CONCLUSION: Considering the complex
      biomechanical behavior of human hard and soft tissues, EV-SGA and NL-FEA did not
      suggest inconsistency in the detection of the quality of strains. Further, the
      methods provided comparable values for the quantification of strains on implants
      supporting maxillary overdentures.

PMID- 19587866
TI  - Accuracy of template-based dental implant placement.
AB  - PURPOSE: The accuracy of a system for image-guided dental implant planning and
      placement based on individually fabricated oral templates was investigated in a
      phantom study. MATERIALS AND METHODS: The study was performed on identical
      phantoms of a partially edentulous mandible. In one phantom mandible (the master
      model), pilot boreholes for dental implants were placed. Computerized tomography
      image data were then acquired. Using a system for template-based dental implant
      placement, identical boreholes were planned on the image data and then reproduced
      in the 10 remaining phantom mandibles (the "slave" models). The resulting
      positions were compared to the positions in the master model using a three
      dimensional digitizer arm. RESULTS: The mean deviation of borehole apex positions
      in the slave phantoms, as compared to the master phantom, was 0.50+/-0.04 mm and
      was below 1 mm in 29 of 30 models. The accuracy was highly reproducible,
      irrespective of the template used and the surgeon involved. CONCLUSIONS: The use
      of templates for image-guided insertion of dental implants is a method with high
      and reproducible accuracy.

PMID- 19587867
TI  - Biomechanical effects of a maxillary implant in the augmented sinus: a three
      dimensional finite element analysis.
AB  - PURPOSE: The biomechanical effects of different strengths of grafted bone,
      bicortical anchorage, and dimensional alterations of a dental implant with
      maxillary sinus augmentation were investigated. MATERIALS AND METHODS: Sixteen
      finite element (FE) models that included five implant lengths, two implant
      diameters, and grafted bone with two levels of stiffness were studied. A
      posterior maxillary model was constructed from computerized tomographic images of
      a human skull, and the implant models were created via computer-aided design
      software (SolidWorks 2006). All materials were assumed to be isotropic and
      linearly elastic. A 45-degree oblique force of 129 N was applied to the buccal
      cusp of the first molar. RESULTS: The von Mises stress was highest in the 7-mm
      long implant. Stresses in cortical and trabecular bone were reduced by at least
      50% for all other implants (length greater than or equal to 8.5 mm) with
      bicortical anchorage. Increasing the length of the bicortically anchored implant
      did not decrease the stress in native bone, but it decreased the stress in sinus
      grafts by at least 20%. The use of a wide implant decreased the stress by 24% to
      42% in cortical bone and 17% to 36% in trabecular bone. Increasing the elastic
      modulus of grafted bone decreased the stress in native bone by approximately 10%.
      CONCLUSIONS: Bicortical fixation of implants and the presence of grafted bone
      with greater stiffness reduced the stresses in native bone. Increasing the length
      of the implant in grafted bone did not reduce the stress in native bone, but it
      did reduce the stress in grafted bone. The effects of implant diameters on
      reducing bone stress are primarily a result of the increased contact area between
      implant and bone. The results of the FE analysis imply that the success of a
      sinus-augmented dental implant is heavily dependent on the implant design and
      rigidity of the bone grafts.

PMID- 19587868
TI  - Autogenous bone graft with or without perforation of the receptor bed: histologic
      study in rabbit calvaria.
AB  - PURPOSE: To evaluate the amount of bone matrix in autogenous block bone grafts
      that were fixed with or without perforation of the receptor bed. MATERIALS AND
      METHODS: Twelve rabbits received two 5-mm circular osteotomies each in the
      anterior parietal region. The bone was removed, perforated, and fixed by a
      titanium screw in the adjacent area, 3 mm from the border of the osteotomies. On
      the contralateral side, six perforations were made in the receptor site before
      the graft was fixated by the titanium screw. After 28 days, the animals were
      sacrificed and specimens were prepared for histologic study. Sections were
      analyzed with regard to the total area of the graft and the percentages of bone
      matrix in the graft, interface, and receptor bed. Analyses using the Wilcoxon
      test (P<.05) were performed. RESULTS: No statistically significant differences
      were found between the groups with or without perforations to the area of the
      graft (P=.85) or the percentage of hard tissue in the grafts (P=.53), the
      interface (P=.65), or the receptor bed (P=.18). CONCLUSION: Based upon this study
      that used a rabbit model with bone grafts placed in the parietal regions,
      cortical perforations of the receptor bone did not improve repair of bone grafts
      and did not increase the amount of bone matrix in the final grafted area.

PMID- 19587869
TI  - Comparison of torque measurements and clinical handling of various surgical
      motors.
AB  - PURPOSE: Modern implant dentistry requires the application of torque during
      various treatment steps. This study investigated seven different surgical motors
      for the accuracy of the applied torque and their reliability. MATERIALS AND
      METHODS: The following surgical motors were evaluated: Chiropro 980 (Bienair),
      INTRAsurg 300 and INTRAsurg 500 (KaVo), Osseocare (Nobel Biocare), Surgic XT
      (NSK), Elcomed SA-200 C (W and H), and Osseo System (XO Dentalcare). The torque
      was measured during typical surgical and prosthetic procedures using a special
      load transfer mechanism for a torque gauge. For each setting, 30 measurements
      were made and means were calculated. RESULTS: The highest percentage shortfall
      was 20.5% at a set torque of 11.4 Ncm (absolute deviation of -2.4 Ncm). The
      highest percentage by which a torque was exceeded was 54.6% (absolute deviation
      of 5.5 Ncm). The lowest value for absolute shortfall was found to be -5.6 Ncm at
      a set torque of 45 Ncm. The highest absolute exceeded was 15 Ncm at a set torque
      of 40 Ncm. Potentially problematic torque values were identified in the low
      torque-value setting, as the implant position may be changed if a machine driver
      applies excessive torque to the first-stage healing screw. In addition, in the
      indication of immediate loading in the high-set-torque group, torque values above
      the critical value of 50 Ncm may be unwittingly applied while working with a set
      torque of 40 Ncm. CONCLUSION: For most of the clinically relevant torque
      settings, precise values were measured, although a few devices delivered
      potentially problematic torque values for some of the indications.

PMID- 19587870
TI  - Development of novel implant abutments using the shape memory alloy nitinol:
      preliminary results.
AB  - PURPOSE: The development of gap-free abutments is a challenging problem, because
      the gap between the implant and the abutment, which is a consequence of current
      manufacturing limitations, can serve as a reservoir for pathogens. This may lead
      to peri-implantitis, a major cause of implant failure. Therefore, the aim of this
      study was to design and fabricate a gap-free abutment using a shape memory alloy
      with improved ability to prevent microleakage at the implant-abutment gap.
      MATERIALS AND METHODS: The abutment was designed using the shape memory alloy
      nitinol and based on mathematical calculations considering the temperature
      related, reversible changes to its crystalline alloy structure. The abutment
      prototypes were tested for their susceptibility to microbes in vitro, under
      static and dynamic conditions, by contaminating the abutments before assembly
      using a bacterial solution. Microbacterial tests were performed after cultivation
      of the implants for 1 week. The results were tested for statistically significant
      differences using the chi-square test. RESULTS: The mathematical calculations met
      the clinical requirements using a contact pressure of 2 3 108 Nm2 with a preload
      of 1.9 kN on cooled abutments. After recooling, the contact pressure was 1.3 Nm2,
      allowing for easy disassembly. Microbacterial analysis revealed no penetration of
      Escherichia coli under static conditions either in the control group or in the
      prototypes. Under dynamic conditions, however, the prototypes showed
      significantly reduced bacterial leakage compared to the controls. CONCLUSIONS:
      The data presented here demonstrate that dental implants fabricated with gap-free
      abutments using a shape memory alloy showed significantly reduced bacterial
      leakage versus conventional implants. This improvement could minimize clinical
      problems such as peri-implantitis and consequently enhance the long-term success
      of dental implants.

PMID- 19587871
TI  - Performance of ultrasonic devices for bone surgery and associated intraosseous
      temperature development.
AB  - PURPOSE: The purpose of this study was to evaluate and to compare the bone
      cutting performance and intraosseous temperature development of three modern
      ultrasonic devices for bone surgery (UDBS). MATERIALS AND METHODS: The following
      UDBS and associated cutting tips (straight bone saws) were used in this study:
      (1) Piezosurgery II professional, tip OT 7 (Mectron); (2) Piezotome, tip BS 1
      (Acteon); and (3) SurgySonic, tip ES007 (American Dental Systems/Gunther Jerney).
      In the experimental setup UDBS, handpieces were immobilized, and bone specimens
      from the middiaphysis of a bovine femur were moved in a longitudinal direction
      under the cutting tip to a standardized depth of 3.0 mm. Intraosseous temperature
      development was measured using a glass-fiber isolated thermocouple. The cutting
      performance was defined by the time required to reach the cutting depth of 3.0
      mm. Statistical analysis was performed using the Wilcoxon rank sum test. RESULTS:
      The median increase (25th through 75th percentiles) of the local intraosseous
      temperature was 3.0 degrees C (2.2 degrees C to 4.2 degrees C) for the
      SurgySonic, 2.2 degrees C (1.8 degrees C to 3.2 degrees C) for the Piezosurgery
      II, and 1.1 degrees C (0.7 degrees C to 1.6 degrees C) for the Piezotome. The
      median cutting performance was 0.31 mm/s (0.11 to 0.46 mm/s) for the Piezotome,
      0.25 mm/s (0.23 to 0.27 mm/s) for the Piezosurgery II, and 0.04 mm/s (0.03 to
      0.05 mm/s) for the SurgySonic. CONCLUSIONS: Among the three tested UDBS, the
      Piezotome and the Piezosurgery II showed a significantly higher cutting
      performance than the SurgySonic. The Piezotome produced the smallest increase in
      intraosseous temperature.

PMID- 19587872
TI  - Comparison of five parameters as risk factors for peri-mucositis.
AB  - PURPOSE: The aim of this study was to identify risk factors for the development
      of clinical signs of peri-implant mucositis and for the presence of periodontal
      pathogens and to determine a possible correlation between these clinical signs
      and the presence of periodontal pathogens. MATERIALS AND METHODS: In 100
      patients, a modified Plaque Index (PI), a modified Sulcular Bleeding Index (BOP),
      and pocket probing depth (PPD) were recorded. Patients with one implant site that
      scored positive for PI, BOP, and PPD greater than or equal to 5 mm were
      considered to have peri-implant mucositis. A sample taken at the implant with the
      deepest pocket was analyzed for periodontal pathogens. Implant surface roughness,
      smoking, augmentation at the implant site, type of dentition, and radiation
      therapy were recorded as possible cofactors in the disease process. RESULTS:
      Thirty-one patients showed clinical signs of peri-implant mucositis and, in 25
      implant sites, periodontal pathogens were found. Smoking showed a statistically
      significant correlation with clinical signs of peri-implant mucositis (univariate
      analysis). For periodontal pathogens at the implant site, the type of dentition
      was statistically significant. In the multivariate analysis of the clinical signs
      of peri-implant mucositis, smoking and radiation therapy were significant
      explanatory variables. Seventy-two percent of the patients showed agreement for
      finding either clinical signs of peri-implant mucositis and periodontal pathogens
      or for no clinical signs and no pathogens. The sensitivity for diagnosis of peri
      implant mucositis was 45%, and the specificity was 84%. CONCLUSIONS: Smoking was
      the most important risk factor in the formation of peri-implant mucositis.
      Radiation therapy was an explanatory variable for the occurrence of inflammation.
      Implant surface roughness, augmentation at the implant site, and type of
      dentition had little influence on clinical signs of peri-implant mucositis. The
      type of dentition influences the periodontal microbiota at the implant site.

PMID- 19587873
TI  - Altered vertical dimension of occlusion: a comparative retrospective pilot study
      of tooth- and implant-supported restorations.
AB  - PURPOSE: Altering the vertical dimension of occlusion (VDO) by increasing the
      interarch distance is common in oral rehabilitation, but little is known about
      the ability of implant patients, who lack sensory perception in implanted
      regions, to adapt to such changes. This study sought to evaluate the outcome of
      increasing VDO in patients restored with implant-supported fixed restorations
      opposed by restored natural teeth or implant-supported restorations. MATERIALS
      AND METHODS: VDO was increased by 3 to 5 mm to address the individual prosthetic
      needs of 30 patients. Group A (control) consisted of 10 patients with fixed
      restorations on natural dentition that opposed the natural dentition in a new VDO
      relationship. Two test groups consisted of 10 patients each, with fixed implant
      supported restorations opposing either the restored natural dentition (group B)
      or fixed implant-supported restorations (group C). After an average follow-up of
      66 months, marginal bone changes were calculated using standardized periapical
      radiographs, and mechanical prosthetic maintenance data were collected from
      patient files. The results were analyzed using Kruskal-Wallis one-way analysis of
      variance to identify significant differences between the groups. RESULTS: All
      patients successfully adapted to the new VDO. Two patients in group B and four in
      group C reported tooth clenching or grinding, which abated after 2 to 3 months
      (P<.05). More bone loss and tooth failures were observed in group A, and more
      mechanical complications, such as porcelain fractures, were observed in group C
      (P<.05). CONCLUSION: Within the limitations of this study, alteration of VDO was
      an acceptable procedure in patients with implant-supported fixed restorations,
      but precautions should be taken to prevent mechanical problems.

PMID- 19587874
TI  - Vertical ridge augmentation using guided bone regeneration (GBR) in three
      clinical scenarios prior to implant placement: a retrospective study of 35
      patients 12 to 72 months after loading.
AB  - PURPOSE: The aims of the current study were to: (1) evaluate the results of
      vertical guided bone regeneration (GBR) with particulate autogenous bone grafts,
      (2) determine clinically and radiographically the success and survival rates of
      82 implants placed in such surgical sites after prosthetic loading for 12 to 72
      months, and (3) compare defects that were treated simultaneously with sinus
      augmentation and vertical GBR to other areas of the jaw treated with vertical GBR
      only. MATERIALS AND METHODS: Eighty-two implants were inserted in 35 patients
      with 36 three-dimensional vertical bone defects. The patients were divided into
      three groups: single missing teeth (group A), multiple missing teeth (group B),
      and vertical defects in the posterior maxilla only (group C). All group C
      subjects were treated simultaneously with sinus and vertical augmentations. All
      patients were treated with vertical ridge augmentation utilizing titanium
      reinforced polytetrafluoroethylene (e-PTFE) membranes and particulated
      autografts. After removal of the e-PTFE membrane, all sites received a collagen
      membrane. RESULTS: At membrane removal, mean vertical augmentation was 5.5 mm (+/
      2.29 mm). Mean combined crestal remodeling was 1.01 mm (+/-0.57 mm) at 12 months,
      which remained stable through the 6-year follow-up period. There were no
      statistically significant differences between the three groups in mean marginal
      bone remodeling. One defect had a bone graft complication (2.78%, 95% CI: 0.00%,
      8.15%). The overall implant survival rate was 100% with a cumulative success rate
      of 94.7%. CONCLUSIONS: (1) Vertical augmentation with e-PTFE membranes and
      particulated autografts is a safe and predictable treatment; (2) success and
      survival rates of implants placed in vertically augmented bone with the GBR
      technique appear similar to implants placed in native bone under loading
      conditions; (3) success and failure rates of implants placed into bone
      regenerated simultaneously with sinus and vertical augmentation techniques
      compare favorably to those requiring only vertical augmentation.

PMID- 19587876
TI  - Implant rehabilitation of the atrophic edentulous maxilla including immediate
      fixed provisional restoration without the use of bone grafting: a review of 1
      year outcome data from a long-term prospective clinical trial.
AB  - PURPOSE: The literature suggests that predictable integration can be achieved
      when dental implant placement is combined with immediate fixed provisional
      restoration in a variety of clinical situations. Fewer data are available,
      however, regarding outcomes for immediate provisional restoration of implants in
      the edentulous maxilla. This report presents 1-year data acquired from a long
      term prospective clinical trial designed to assess outcomes following the
      immediate provisional fixed restoration of implants in the atrophic edentulous
      maxilla without the use of bone augmentation. MATERIALS AND METHODS: Fifty-one
      subjects diagnosed with an atrophic edentulous maxilla received a total of 306
      implants (six implants per subject) followed by fixed provisional restoration
      within 24 hours of implant placement. No subjects underwent grafting to enhance
      bone volume in preparation for implant treatment. Data acquired included bone
      quantity and quality, implant dimensions, implant locations, and implant
      placement stability. Subjects returned for 1-year follow-up examinations to
      assess implant integration and restoration function. Periapical radiographs were
      obtained and compared to baseline images to assess marginal bone height
      maintenance. RESULTS: At the 3-month follow-up examination, 294 of 306 implants
      placed in 51 subjects were found to be integrated. This represents a cumulative
      implant survival rate of 96%. At the 1-year follow-up examination, mean marginal
      bone loss of 0.5 mm was noted, with no further loss of implants. CONCLUSIONS:
      These results support the contention that predictable long-term outcomes may be
      obtained for the atrophic edentulous maxilla when treated with an implant
      rehabilitation protocol that includes immediate fixed provisional restoration
      without the use of bone grafting. This strategy offers a promising treatment
      alternative for the patient with an atrophic edentulous maxilla.

PMID- 19587875
TI  - Comparison of tilted versus nontilted implant-supported prosthetic designs for
      the restoration of the edentuous mandible: a biomechanical study.
AB  - PURPOSE: The purpose of the study was to evaluate, using finite element analysis,
      the stress patterns induced in cortical bone by three distinct implant-supported
      prosthetic designs. MATERIALS AND METHODS: The first two models consisted of a
      prosthesis supported by four implants, the distal two of which were tilted, with
      different cantilever lengths (5 mm and 15 mm). The third design consisted of a
      prosthesis supported by five conventionally placed implants and a 15-mm
      cantilever. RESULTS: In the tilted model with 5-mm cantilever and in the
      nontilted model, the maximum value of compressive stress (-18 MPa) was found near
      the cervical area of the distal implant. Higher values for compressive stress
      were predicted near the cervical area of the distal implant in the tilted model
      with a 15-mm cantilever, as compared to the tilted model with the 5-mm
      cantilever. For the tilted model with the 5-mm cantilever, peak values of tensile
      stress were predicted near the cervical area of both the distal (1.25 MPa) and
      the mesial implants (2.5 MPa). For the nontilted model, the peak value was found
      near the cervical area of the in-between implant (5 MPa). For the tilted model
      with 15-mm cantilever, tensile stress values were higher than in the tilted model
      with 5-mm cantilever. CONCLUSIONS: No significant difference in stress patterns
      between the tilted 5-mm and the nontilted 15-mm configuration was predicted. The
      tilted configuration with a 15-mm cantilever was found to induce higher stress
      values than the tilted configuration with a 5-mm cantilever.

PMID- 19587877
TI  - Palatal positioning of implants in severely resorbed edentulous maxillae.
AB  - PURPOSE: The aim of this study was to evaluate implant-supported restorations
      supported by palatally positioned implants as an alternative treatment for
      rehabilitation of the atrophic maxilla and to assess the satisfaction of patients
      with the results. MATERIALS AND METHODS: A retrospective case study was conducted
      on completely edentulous subjects who received palatally positioned implants
      (placed and loaded) between January 2000 and January 2004. Inclusion criteria
      were patients with severely resorbed edentulous maxillae (Class IV or V maxillary
      atrophy, according to the Cawood and Howell classification) who requested implant
      supported restorations and had a follow-up period of at least 24 months after
      implant loading. Panoramic radiographs and maxillary computerized tomograms had
      been made for all patients prior to treatment. Mesial and distal implant bone
      loss was measured on panoramic radiographs, and the largest value was designated
      as the bone loss for the implant in question. Subjects indicated their degree of
      satisfaction with the new prosthesis after 12 months on a visual analogue scale.
      RESULTS: Sixty-nine patients with severely resorbed edentulous maxillae were
      included in the study. Four hundred and ninety implants (six to eight in each
      patient) were placed to support 69 fixed prostheses; 330 were in palatal
      positions and 160 were in molar positions (84 over the crest in the first molar
      position and 76 in anatomic buttresses). The success rate of palatally positioned
      implants was 97.8% (323/330). The mean bone loss of implants with palatal
      anchorage after 2 years of loading was 0.61 mm (range, 0 to 3.10 mm). All
      patients had stable prostheses at the end of the observation period. Patients
      were satisfied with comfort and stability, ability to speak, ease of cleaning,
      esthetics, and function of the prosthesis. CONCLUSION: Implants placed in a
      palatal position may be a viable alternative for rehabilitation of the atrophied
      maxilla.

PMID- 19587878
TI  - Dental implants in persons with severe epilepsy and multiple disabilities: a long
      term retrospective study.
AB  - PURPOSE: A retrospective study on the performance of endosseous implants in a
      population of patients with severe epilepsy and additional motor and/or
      intellectual impairments was performed. MATERIALS AND METHODS: All residents of
      an inpatient center for persons affected by severe, refractory epilepsy and
      multiple disabilities who received endosseous implants between 1991 and April
      2007 were included in the study. Implant survival was analyzed using the Kaplan
      Meier method. A subset of patients who were treated between 1991 and 2004 was
      invited to participate in a clinical and radio?graphic evaluation in 2004 and
      2005. RESULTS: A total of 61 patients were treated between 1991 and April 2007
      (n=134 implants). Three of these implants in three different patients failed
      during the observation period, demonstrating an estimated probability of
      functional implant survival of 97.6% (SE 1.4%) after 16 years. In patients who
      were seen during the clinical evaluation in 2004 (n=76 implants), only mild
      inflammation of the peri-implant mucosa was generally observed (Gingival-Bleeding
      Index=1), despite the fact that the level of oral hygiene was considered
      inadequate around 55 of 76 implants (72%). Obvious signs of drug-induced gingival
      hyperplasia in relation to the implants were not observed. Probing depths
      averaged approximately 2 mm. Stable marginal bone levels were observed on the
      radiographs. CONCLUSIONS: Dental implant treatment in a population of patients
      with severe epilepsy and additional disabilities seems to be a viable treatment
      option. Implant loss is rare. Although adequate plaque control was not feasible
      in all patients, marginal bone levels remained stable.

PMID- 19587879
TI  - Computer-guided implant placement: 3D planning software, fixed intraoral
      reference points, and CAD/CAM technology. A case report.
AB  - The aim of this article is to explain the use of a computer-aided three
      dimensional planning protocol in combination with previously placed mini-implants
      and computer-aided design/computer-assisted manufacture (CAD/CAM) technology to
      restore a completely edentulous patient. Mini-implants were used to establish a
      setup for computerized tomographic imaging and a surgical template. The software
      and its three-dimensional simulation allowed the authors to plan ideal implant
      placement, digitally integrating the future prosthetic and anatomic situations to
      design the definitive superstructure. The CAD/CAM superstructure is produced
      digitally with a precise fit and occlusion and good esthetics, and is placed
      immediately after surgery.

PMID- 19587880
TI  - The role of gutka chewing in oral submucous fibrosis: a case-control study.
AB  - OBJECTIVE: To learn about the use of various chewing substrates, such as areca
      nut and gutka, among subjects with oral submucosal fibrosis (OSMF) and controls
      with no oral mucosal lesions. MATERIALS AND METHODS: In this hospital-based case
      control study, 220 patients with OSMF were selected and compared with matched
      controls with regard to dietary habits, including spice use, smoking history, and
      preference for chewing substrates. Relative risk of various chewing habits was
      calculated using an odds ratio and logistic regression analysis to understand the
      influence of chewing habits, spices, and smoking on the development of OSMF.
      Discriminate analysis was employed to determine which risk factors were valid and
      reliable discriminators between individuals with or without OSMF. RESULTS: The
      relative risk of developing oral submucosal fibrosis was highest with gutka
      chewing habit (relative risk, 1,142.4), which was significant (P < .01) at 95%
      confidence interval. The next highest relative risk for development of oral
      submucosal fibrosis was observed for the combination of gutka with other chewing
      habits. The relative risk of developing submucosal fibrosis increased with the
      frequency of chewing habit up to 15 times daily with a duration of habit up to 4
      years. The relative risk decreased with chewing frequency beyond 15 times daily
      and 4 years in duration. Logistic regression and discriminative analysis show
      that chewing areca nut and gutka, especially daily, greatly influence the
      development of submucosal fibrosis. CONCLUSION: This study suggests that chewing
      commercially available areca-nut preparations such as gutka is strongly
      associated with the development of oral submucosal fibrosis.

PMID- 19587882
TI  - A paradigm shift in oral and maxillofacial imaging.

PMID- 19587881
TI  - The adverse effect of self-etching adhesive systems on dental pulp after direct
      pulp capping.
AB  - OBJECTIVES: To evaluate the histopathological changes in mechanically exposed dog
      pulps capped with three self-etching adhesive systems. MATERIAL AND METHODS:
      Seventy-two Class V cavities were prepared under rubber dam isolation in dogs.
      The pulps were exposed and capped with Clearfil SE Bond (Kuraray), Imperva
      FluoroBond (Shofu), Prompt L-Pop (3M ESPE), and Dycal (Dentsply; control capping
      agent), respectively. Histopathological examination of the teeth was performed at
      7, 14, and 30 days postoperatively. Hematoxylin-eosin staining was performed to
      assess the inflammatory cell response, tissue disorganization, and hard tissue
      formation. Brown and Brenn staining was used to detect the presence of bacteria.
      The data were analyzed by Kruskal-Wallis and Nemenyi tests. RESULTS: Most pulps
      showed moderate to severe inflammatory responses. Hard tissue formation appeared
      at 14 to 30 days. Positive bacterial staining was observed in most specimens in
      experimental groups. The histological changes in the pulps of the experimental
      groups were more pronounced than in the control group. Differences in
      inflammatory response, tissue disorganization, and hard tissue formation were
      observed among teeth treated with the three self-etching systems. CONCLUSION:
      Microleakage has a critical influence on pulpal repair. It is not beneficial to
      cap the pulp with self-etching adhesive systems. Diverse pulpal responses were
      observed to the self-etching adhesive systems, and the histological changes were
      more pronounced than in the control pulps treated with Dycal. The effects of the
      self-etching adhesive systems are such that these materials require further study
      to address issues of bacterial microleakage during placement of restorations.

PMID- 19587883
TI  - Implant-prosthetic rehabilitation for a patient with monolateral cleft lip and
      palate: a clinical report.
AB  - Cleft lip and palate (CLP) is a malformation of genetic derivation. For patients
      affected by CLP, procedures of guided bone regeneration by autologous bone
      grafting are recognized as the most effective to close oronasal communication.
      The residual gap of alveolar ridge, determined by the absence of 1 or more
      permanent teeth, can be completed by implant-prosthetic rehabilitation. This kind
      of rehabilitation for patients with CLP has the aim of completing dental
      reconstruction by avoiding sacrifice of adjacent teeth and preserving symmetric
      appearance. This article describes the rehabilitation of an 18-year-old patient
      affected by right unilateral CLP with use of a titanium implant supporting a
      single crown to replace the lateral incisor. The technique used was particularly
      helpful for this cleft case, in which a bone deficit subsisted after secondary
      bone grafting. An additional bone grafting procedure was performed at the time of
      implant placement to achieve the best functional and esthetic results.

PMID- 19587884
TI  - An adventurous habit of bottle-cap opening resulting in an endodontic-periodontal
      lesion: a case report.
AB  - An unusual case of an endodontic-periodontal lesion in a 29-year-old man
      resulting from a habit of opening beer bottle (metal) caps using his mandibular
      left molar is reported. The patient had been a chronic alcoholic with several
      emotional problems and was unaware of the injurious nature of his habit. Thus,
      the importance of a detailed case history and assessment of psychosocial aspects
      for an accurate diagnosis of such conditions is highlighted.

PMID- 19587885
TI  - Endodontic therapy of a mandibular third molar with 5 canals: a case report.
AB  - Endodontic treatment of third molars often becomes part of comprehensive
      treatment plans, as it represents a more conservative and less invasive approach
      than its therapeutic alternatives. The frequency of anatomic variations in
      mandibular molars, particularly root canal configuration, requires 2 periapical
      radiographs from different angles. Upon reading and interpretation of the
      radiographs, the clinician should consider the anatomy and level of difficulty of
      the endodontic procedure and refer the patient to an endodontist, if deemed
      necessary. The present article discusses the successful treatment and
      preservation of a mandibular third molar with 5 root canals, as well as methods
      for its clinical management.

PMID- 19587886
TI  - Posttraumatic head injury resulting in spasticity disorders and oral injury:
      application of prosthodontic skills for tissue protection--a case report.
AB  - Patients who have experienced significant brain injury (such as hemorrhagic
      stroke or trauma) can suffer brain damage that leads to altered neurologic
      functioning. One such ill effect is the development of aberrant mandibular
      reflexes that may inflict serious trauma to oral and labial tissues. As primary
      oral health care providers, dental clinicians may be called upon to function as
      part of the medical team managing the patient. This case report reviews one such
      scenario in which the unique skills of trained specialists were used to provide a
      protective oral device to allow for tissue protection and healing.

PMID- 19587887
TI  - Treatment of localized gingival recessions using enamel matrix derivative as an
      adjunct to laterally sliding flap: 2 case reports.
AB  - Predictable and optimal coverage of exposed root surfaces is an important goal in
      periodontal plastic surgery. In this report, recession coverage was performed as
      laterally sliding flap technique with the adjunctive use of enamel matrix
      derivative (EMD). The cases of 2 female patients with gingival recession on the
      maxillary canines are presented with 1-year follow-up observation. Initial
      vertical gingival recessions were 4.0 mm each, with a probing depth of 1.0 mm.
      The surgical procedure immediately produced a marked reduction in gingival
      recessions. In the course of healing, the soft tissue margin on the operated
      teeth showed some shrinkage in the first months. After 1 year, complete root
      coverage (100%) was observed, with a probing depth of 0.5 mm and 5.0-mm gain of
      clinical attachment in both cases, and there was 0.5-mm creeping tissue above the
      cemento-enamel junction. Within the limits of these cases, the results
      demonstrated the possibility of treating human buccal recessions with EMD plus
      laterally sliding flap, with predictable root coverage and clinical attachment
      gain.

PMID- 19587888
TI  - Effect of delayed light polymerization of a dual-cured composite base on
      microleakage of Class 2 posterior composite open-sandwich restorations.
AB  - OBJECTIVE: To determine the effect of delayed start of light polymerization of a
      dual-cured composite base on the microleakage of Class 2 open-sandwich composite
      restorations. METHOD AND MATERIALS: Fifty extracted human molars were used to
      prepare Class 2 mesio-occlusal and disto-occlusal slot preparations. Teeth were
      randomly divided into 2 groups and restored with a base of dual-cured composite
      in the proximal box and a top layer of light-cured composite. Group I was
      restored with a 1-step dual-cured bonding agent; group II was restored with a 2
      step dual-cured bonding agent. Five subgroups were created according to the
      method of polymerization of the dual-cured composite: (A) self-cured, (B) light
      cured immediately, (C) light-cured 30 seconds after placement, (D) light-cured 60
      seconds after placement, and (E) light-cured 120 seconds after placement.
      Restorations were stored for 1 week at 37 degrees C and 100% relative humidity,
      thermocycled (2,000 times, 5 degrees C to 55 degrees C, 15-second dwell), and
      immersed in a 1% aqueous solution of methylene blue for 24 hours at 37 degrees C.
      Samples were sectioned mesiodistally, and dye penetration at enamel, dentin, and
      cementum margins was scored under a stereomicroscope using an ordinal scoring
      system. RESULTS: Statistical analysis using analysis of variance (ANOVA) on ranks
      showed that the dual-cured composite light polymerized 1 minute after placement
      exhibited the lowest microleakage (P < .05) in both bonding agent groups.
      CONCLUSION: Delayed, rather than immediate, light polymerization of the dual
      cured composite base reduced microleakage in Class 2 open-sandwich restorations.

PMID- 19587889
TI  - Does harvesting connective tissue grafts from the palate cause persistent sensory
      dysfunction? A pilot study.
AB  - OBJECTIVE: The use of connective tissue grafts is a proven, effective treatment
      modality. This study examines whether harvesting connective tissue grafts from
      the palate causes persistent sensory dysfunction. METHODS AND MATERIALS: Fourteen
      patients who had received at least 1 graft were included. Neurosensory tests at
      the palate performed postoperatively included minimal 2-point discrimination,
      soft-touch discrimination, pin-tactile discrimination, and thermal
      discrimination. Measurements were taken at 3 sites each: 5, 10, and 15 mm from
      the palatal tissue margin at canines, premolars, and first molars. RESULTS: Eight
      patients had 1 graft, and 6 patients had 2 grafts harvested from their palate.
      Twelve patients had never noticed any dysfunction. Two patients reported a
      persistent numbness or a rough palatal surface. Statistically significant
      differences between donor sites and nondonor sites were shown by 2-point
      discrimination 5 mm from the margin of canines (6.57 mm +/- 3.79 mm at donor
      sites and 4.71 mm +/- 4.14 mm at nondonor sites, P = .01). Repeated-measures
      analysis of variance showed statistically significant differences between donor
      sites and nondonor sites for measurements taken 5 and 10 mm from the margin of
      all included teeth (P = .02). CONCLUSIONS: Some sensory changes can occur after
      graft harvesting from the palate.

PMID- 19587890
TI  - Pulp reactions in human teeth capped with self-etching or total-etching adhesive
      systems.
AB  - OBJECTIVE: Restorative procedures of the dentin-pulp complex stimulate damages
      that, depending on the technique and materials used, may induce pulpal reactions.
      The purpose of this study was to evaluate immunochemistry, morphologic, and
      morphometric pulpal alterations of human teeth pulps capped with self-etching or
      total-etching adhesive systems. METHOD AND MATERIALS: Thirty human third molars
      were restored with a resin-based composite and adhesive system, either Clearfil
      (Kuraray; n = 10) or Scotchbond (3M ESPE; n = 10). After 7, 30, or 60 days, the
      teeth were extracted and longitudinally sectioned. The pulps were removed for
      histopathologic and immunochemistry evaluation for interferon (IFN)-gamma, tumor
      necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS). RESULTS:
      The density of fibrous connective tissue was significantly higher after 30 days
      in both groups (P < .001). Congestion, hemorrhage, calcification, and swelling of
      the odontoblasts were similar in both groups. The total capillary area was
      significantly higher after 7 and 30 days in both groups. Positive immunoreactions
      for iNOS were found in 1 case (20%) of the 30-day Scotchbond group.
      Immunoreactions for IFN-gamma were positive in a few cells in 1 case (20%) of the
      7-day Clearfil group. There were no positive immunoreactions for TNF-alpha in any
      case. CONCLUSION: No inflammatory reactions, necrotic areas, or severe
      immunoreactions for proinflammatory cytokines were found, suggesting
      biocompatibility of self-etching or total-etching adhesive systems when placed
      directly on dentin.

PMID- 19587893
TI  - Effect of bone crest to contact point distance on central papilla height using
      embrasure morphologies.
AB  - OBJECTIVE: To determine whether embrasure morphology can affect the association
      between bone crest-contact point distance and central papilla height in esthetic
      dentistry. METHOD AND MATERIALS: The central papilla was visually assessed in 310
      adults using standardized periapical radiographs of the maxillary central
      incisors. The following vertical distances were measured: bone crest to contact
      point, proximal cementoenamel junction to contact point, and papilla height. The
      horizontal distance measured was the interdental width. Subjects were divided
      into 4 groups according to interdental width and proximal cementoenamel junction
      contact point distance: narrow-long, narrow-short, wide-long, and wide-short.
      RESULTS: In subjects with papilla recession, the longer the bone crest-contact
      point distance, the greater the mean papilla height in all study groups except
      the narrow-long group. Significant correlations were found between papilla height
      and bone crest-contact point distance in subjects with recession. CONCLUSIONS:
      Various embrasure morphologies did not affect central papilla height in subjects
      with papilla recession. However, other factors may affect the central papilla
      height, and further study of these factors is necessary.

PMID- 19587892
TI  - Dermal fibrosis and calcification secondary to burn injury.
AB  - A case of fibrosis in the cheek of a 42-year-old woman is presented. The
      panoramic radiograph showed a well-defined, round radiopacity in the maxillary
      right third molar region. Other techniques revealed that it was a
      superimposition. The lesion was hard and painless and associated with
      hypertrophic scarring secondary to a burn injury many years earlier. Clinicians
      must be aware of the radiologic image of this fibrosis, so as not to confuse it
      with other radiopaque lesions of hard tissue origin that occur in both arches. A
      differential diagnosis is described.

PMID- 19587891
TI  - Anticalculus efficacy of a new dentifrice.
AB  - OBJECTIVE: The Volpe and Manhold Index (VMI) was used to evaluate the
      anticalculus efficacy of the dentifrice Fluor Kin antisarro, used on adults twice
      a day for 2 minutes over 3 months, in comparison with the dentifrice Lacer.
      METHOD AND MATERIALS: A clinical study in which 48 adults took part was designed.
      The presence of calculus was determined at baseline (VMI), a tartrectomy was
      performed, and the patients were instructed to brush their teeth twice a day for
      2 minutes, using a medium-bristled toothbrush with a commercial dentifrice
      containing 0.2% aldioxa and 1.9% sodium monofluorophosphate. Three months later,
      VMI was determined again. After 2 weeks, a new tartrectomy was performed on the
      same patients, and the subjects were instructed to brush their teeth as before,
      this time with the study dentifrice based on 0.32% sodium fluoride, 4.1%
      tetrapotassium pyrophosphate, 2.0% PVM/MA (methylvinylether/maleic acid)
      copolymer (Gantrez S), 1.0% provitamin B5, and 0.2% vitamin B3. After an
      additional 3 months, dental calculus was determined again. RESULTS: The study
      dentifrice showed a significant reduction in VMI in relation to the initial
      situation (P = .009). There were also significant differences in VMI values
      between the 2 dentifrices (P = .010). VMI differences were not significant for
      either dentifrice when analyzed by gender, tobacco use, and toothbrushing
      frequency before starting the study. CONCLUSIONS: Brushing twice a day for 2
      minutes with Fluor Kin antisarro effectively reduces supragingival calculus.

PMID- 19587894
TI  - Misfit of suprastructures on implants processed by electrical discharge machining
      or the Cresco method.
AB  - OBJECTIVE: To assess the accuracy of fit of frameworks on implants processed with
      electrical discharge machining (EDM) or the Cresco technique (Astra Tech). METHOD
      AND MATERIALS: On 12 identical master casts with implants at positions 9(21),
      11(23), and 13(25), high-gold alloy frameworks were produced by standard casting
      procedure. Six frameworks were used for the Cresco technique (group CRE) by
      employing specific fixed partial denture supports. The remaining 6 frameworks
      were cast with prefabricated gold copings and served as control. The finished
      frameworks were screwed onto implant 25 of the corresponding master cast.
      Dimensions of the marginal gaps were measured at 4 locations on each implant
      under the scanning electron microscope, applying the replica technique.
      Subsequently, the control group was processed by EDM (SAE EDM 2000) (group EDM)
      and analyzed alike. Statistical analysis of the results was performed with
      Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The mean marginal gaps were
      measured as follows (CRE/EDM/control): position 25: 0.0 microm/1.0 +/- 1.6
      microm/1.5 +/- 2.1 microm; position 23: 5.2 +/- 5.6 microm/18.7 +/- 29.3
      microm/23.6 +/- 30.7 microm; and position 21: 36.0 +/- 21.6 microm/40.7 +/- 31.0
      microm/46.0 +/- 41.1 microm. The only statistically significant difference was
      found at location 23 between group CRE on one side and both group EDM and control
      on the other side. The strong increase of misfit for group CRE from location 23
      to location 21 indicates that laser welding is the crucial parameter in this
      technique. CONCLUSION: The Cresco technique has a potential to reduce the
      marginal gap between implants and suprastructures.

PMID- 19587895
TI  - Genome-wide analysis predicts DNA structural motifs as nucleosome exclusion
      signals.
AB  - Several factors are known to determine chromatin organization. However, the role
      of non-canonical DNA structure has not been studied in this context. Our recent
      observations indicated a widespread role of a particular non-canonical DNA
      structure, the G-quadruplex, or G4 motifs, in gene regulation. Herein, we first
      analyzed potential G4 (PG4) motif occurrence vis-a-vis nucleosome occupancy
      signals. Genome-wide analysis using reported nucleosome positions in
      Saccharomyces cerevisiae and human (ENCODE regions and 3239 promoters) showed
      exclusion of nucleosomes by regions that have a relatively high density of PG4
      motifs (P < 0.0001). This was supported by the enrichment of PG4 motifs within
      DNase I hypersensitive sites, which generally exclude nucleosomes. Based on
      these, we asked whether PG4 motifs had any distinct regulatory function. Two non
      overlapping gene-sets in humans were tested-with PG4-enriched (Set I) or
      nucleosome-enriched (Set II) promoters. Gene-sets I and II were enriched in
      distinct functions: apoptosis and cellular signaling vs. development and immunity
      related, respectively (P < 0.01). Sets I and II also showed different tissue
      specific expression in 35 normal human tissues. In S. cerevisiae, we noted
      significant enrichment of PG4 motif regulated genes in cellular response to heat
      shock, while genes with nucleosome-enriched promoters were not significantly
      represented. Our results show a structural motif as a possible nucleosome
      exclusion signal for the first time, and predict an alternate/additional
      regulatory role of G4 motifs, which could be distinct from gene regulation by
      remodeling of nucleosomes.

PMID- 19587899
TI  - Experimental evidence for interactions between anions and electron-deficient
      aromatic rings.
AB  - This feature article summarizes our research aimed at using electron-deficient
      aromatic rings to bind anions in the context of complementary research in this
      active field. Particular attention is paid to the different types of interactions
      exhibited between anions and electron-deficient arenes in solution. The 120+
      references cited in this article underscore the flurry of recent activity by
      numerous researchers in this field, which was relatively nascent when our efforts
      began in 2005. While the interaction of anions with electron-deficient aromatic
      rings has recently garnered much attention by supramolecular chemists, the
      observation of these interactions is not a recent discovery. Therefore, we begin
      with a historical perspective on early examples of anions interacting with
      electron-deficient arenes. An introduction to recent (and not so recent)
      computational investigations concerning anions and electron-deficient aromatic
      rings as well as a brief structural survey of crystalline examples of this
      interaction are provided. Finally, the limited solution-based observations of
      anions interacting with electron-deficient aromatic rings are summarized to
      introduce our current investigations in this area. We highlight three different
      systems from our lab where anion-arene interactions have been investigated.
      First, we show that tandem hydrogen bonds and anion-arene interactions augment
      halide binding in solution. Second, a crystallographic and computational study
      highlights the multiple types of interactions possible between anions and
      electron-deficient arenes. Third, we summarize the first example of a class of
      designed receptors that emphasize the different types of anion-arene interactions
      possible in solution.

PMID- 19587900
TI  - A macrocyclic approach to transition metal and uranyl Pacman complexes.
AB  - Multielectron redox chemistry involving small molecules such as O2, H2O, N2, CO2,
      and CH4 is intrinsic to the chemical challenges surrounding sustainable, low
      carbon energy generation and exploitation. Compounds with more than one metal
      reaction site facilitate this chemistry by providing both unique binding
      environments and combined redox equivalents. However, controlling the aggregation
      of metal cations is problematic, as both the primary coordination spheres of the
      metals and the metal-metal separations have to be defined carefully. We described
      recently a series of pyrrole-based macrocyclic ligands designed to manage metal
      aggregation and form molecular multimetallic complexes. In particular, we have
      shown that these compartmentalised Schiff-base calixpyrroles generally form rigid
      Pacman complexes that prescribe well-defined, metallo microenvironments within
      the molecular cleft. This article will review the development of this chemistry
      and its context, and will highlight structural facets and reaction chemistry of
      metal complexes from across the periodic table.

PMID- 19587902
TI  - Oxidative coupling of amines and ketones by combined vanadium- and
      organocatalysis.
AB  - The combination of vanadium- and organocatalysis allows for the direct oxidative
      coupling of cyclic tertiary amines with non-activated ketones without the need
      for preformed leaving groups.

PMID- 19587901
TI  - Construction of trimeric porphyrin-fullerene-porphyrin stacks within surface
      derived pores of nano-scale dimensions.
AB  - A new efficient strategy of a zinc porphyrin based yoctowell cavity as a receptor
      for the formation of stable inclusion complexes of fullerenes via pi-electronic
      donor-acceptor and hydrophobic interactions, and finally anionic porphyrin used
      as a cover to the wells.

PMID- 19587903
TI  - Colorimetric detection of microRNA and RNase H activity in homogeneous solution
      with cationic polythiophene derivative.
AB  - A colorimetric assay for convenient detection of miRNA and RNase H activity was
      established in a homogeneous and label-free manner based on conformational and
      colorimetric changes of a polythiophene derivative (PMNT) in the duplex of
      DNA/PMNT and triplex of DNA/miRNA/PMNT.

PMID- 19587904
TI  - Selective ratiometric detection of mercury(II) ions in water with an acridizinium
      based fluorescent probe.
AB  - The integration of a selective Hg2+ receptor unit, 1,4-dioxa-7,13-dithia-10
      azacyclopentadecane, into the 9-aminoacridizinium fluorophore provides a
      fluorescent probe which allows a selective ratiometric detection of Hg2+ in
      water.

PMID- 19587905
TI  - Conformationally controlled, thymine-based alpha-nucleopeptides.
AB  - Rigid peptide backbones and backbone-to-side chain H-bonds permit the design of
      alpha-nucleopeptides with known 3D-structure; thymine-thymine base pairing is
      also observed.

PMID- 19587906
TI  - Crystal structure determination of the elusive paracetamol Form III.
AB  - The previously unknown crystal structure of the elusive Form III of paracetamol
      has been solved using high quality laboratory X-ray powder diffraction (XRPD)
      data and state-of-the-art crystal structure prediction (CSP).

PMID- 19587907
TI  - Formation of a nitrate zipped dimeric capsule and un-zipping by chloride doping.
AB  - A dimeric capsular aggregation of two units of arene capped tripodal receptor
      stitched together by a planar anion, such as nitrate, and ruptured by a spherical
      anion like chloride in aqueous medium.

PMID- 19587908
TI  - Room-temperature synthesis of nanocrystalline Ag2S and its nanocomposites with
      gold.
AB  - This manuscript demonstrates a room-temperature synthesis for Ag2S nanocrystals
      and their nanocompsites with Au and the Au could be deposited only at a single
      site on each Ag2S seed nanocrystal, where in contrast, Ag2S could grow
      homogeneously on Au seed nanocrystals, resulting in core-shell Au@Ag2S
      nanoparticles, which still possessed the optical properties of Au nanocrystals;
      this facile synthesis could be employed towards fabricating a variety of
      nanocomposites with interesting structures and tailored functionalities.

PMID- 19587909
TI  - Surface plasmon-coupled directional emission based on a conformational-switching
      signaling aptamer.
AB  - We have observed highly polarized and directional surface plasmon-coupled
      emission of a signaling aptamer due to the binding of a target thrombin with the
      aptamer, which induces conformational switching.

PMID- 19587910
TI  - High-resolution cross-reactive array for alkaloids.
AB  - A high-resolution cross-reactive array capable of classifying alkaloids over a
      range of concentrations was generated by systematic introduction of a nitroindole
      analog into a hydrophobic pocket within a DNA three-way junction to match
      structural motifs presented by the analytes.

PMID- 19587912
TI  - Hydrogen-bonded dimer stacking induced emission of aminobenzoic acid compounds.
AB  - A series of aminobenzoic acid crystals with stacking-induced emission properties
      has been achieved and the packing structures of the hydrogen-bonded acid dimers
      provided an explanation for the emission characteristics of the crystals.

PMID- 19587911
TI  - Selective labeling of tag-fused protein by tryptophan-sensitized luminescence of
      a terbium complex.
AB  - A Tb3+ complex with two di(2-picolyl)amine (DPA) moieties and an oligo-aspartate
      peptide containing a tryptophan residue have been designed as a new binding pair
      for use in protein labeling.

PMID- 19587913
TI  - 7-mercapto-4-methylcoumarin as a reporter of thiol binding to the CdSe quantum
      dot surface.
AB  - Interaction of 7-mercapto-4-methylcoumarin with the surface of core-shell CdSe
      ZnS quantum dots leads to characteristic absorption and emission bands that are
      excellent reporters for thiol interactions at the nanoparticle surface.

PMID- 19587914
TI  - A self-supporting monolith of highly aligned carbon nanotubes as device structure
      for sensor applications.
AB  - A novel approach towards fabricating free-standing and self-supporting highly
      aligned CNT arrays with integrated top and bottom contacts for the design and
      implementation of future CNT-based sensor devices is reported.

PMID- 19587915
TI  - {Ge9R3Cr(CO)5}- and {Ge9R3Cr(CO)3}-: a metalloid cluster (Ge9R3-) as a flexible
      ligand in coordination chemistry [R=Si(SiMe3)3].
AB  - The reactions of the metalloid cluster {Ge9[Si(SiMe3)3]3}- with Cr(CO)5COE
      (COE=cyclooctene) and Cr(CO)3(CH3CN)3 lead to the new cluster compounds
      {Ge9[Si(SiMe3)3]3Cr(CO)5}- and {Ge9[Si(SiMe3)3]3Cr(CO)3}-, whose structural and
      electronic properties are presented.

PMID- 19587917
TI  - Nanoenergetic materials: boron nanoparticles from the pyrolysis of decaborane and
      their functionalisation.
AB  - The surfaces of boron nanoparticles 10-150 nm in diameter, prepared by gas phase
      pyrolysis of decaborane vapour at 1 atm and 700-900 degrees C, can be halogenated
      by treatment with Br2 or XeF2; the surface halogenation somewhat increases the
      onset temperature for the oxidation of the particles under O2.

PMID- 19587916
TI  - Facile controlled preparation of gold nanoparticles with amphiphilic
      thiacalix[4]arene as reductant and stabilizer.
AB  - A facile controlled synthesis method of gold nanoparticles (AuNPs) under mild
      conditions has been developed by combining the stabilization ability of
      amphiphilic thiacalixarene and the reduction ability of phenolic moieties
      together, and the particle sizes of AuNPs can be readily controlled by only
      adjusting the feeding ratio of Au/S.

PMID- 19587918
TI  - The design, synthesis and evaluation of hypoxia-activated pro-oligonucleotides.
AB  - Hypoxia-activated pro-oligonucleotides were synthesized through the commercial
      phosphoramidite method, and could be readily cleaved to form normal oligos with
      good hypoxia selectivity in vitro under the effect of reductases, as well as in
      tumor cell extract.

PMID- 19587920
TI  - Site-isolated, intermolecularly photocrosslinkable and patternable dendritic
      quinacridones.
AB  - Quinacridone-cored dendrimers with photocrosslinkable cinnamate moieties on the
      periphery can be patterned down to 5 micron features while retaining
      luminescence.

PMID- 19587919
TI  - Cell-induced intracellular controlled release of membrane impermeable cysteine
      from a mesoporous silica nanoparticle-based drug delivery system.
AB  - A mesoporous silica nanoparticle-based intracellular cysteine delivery system
      that could be induced and regulated by cell-produced natural antioxidants was
      synthesized.

PMID- 19587921
TI  - Water/oil microemulsion for the preparation of robust La-hexaaluminates for
      methane catalytic combustion.
AB  - Robust and highly effective Fe-substituted and non-substituted La-Hexaaluminate
      methane combustion catalysts have been prepared via coprecipitation in "water
      pools" of Water/Oil microemulsions with dual nonionic surfactants, followed by
      ethanol supercritical drying and post-annealing.

PMID- 19587922
TI  - Facile and predictable synthesis of dual mesoporous-mesosize nanostructures
      through thermally-driven self-assembly of nanodroplets.
AB  - Dual mesoporous-mesosize nanostructures, of interest in water purification and
      clean energy generation, are prepared by a facile and predictable method that
      combines the thermally-driven self-assembly of liquid nanodroplets with gas
      reactants.

PMID- 19587923
TI  - Photoelectrochemical conversion of NO3(-) to N2 by using a photoelectrochemical
      cell composed of a nanoporous TiO2 film photoanode and an O2 reducing cathode.
AB  - Photoelectrochemical conversion of nitrate anions into dinitrogen was
      successfully achieved by using a photoelectrochemical cell composed of a
      nanoporous TiO2 film photoanode and an O2 reducing cathode in the presence of
      NH3, which can be regarded as a model of denitrification and is of importance for
      environmental cleaning.

PMID- 19587925
TI  - A new bifunctional chelator for copper radiopharmaceuticals: a cage amine ligand
      with a carboxylate functional group for conjugation to peptides.
AB  - A new sarcophagine cage amine ligand with a pendent carboxylate functional group
      has been synthesised; the ligand has been conjugated to tumour targeting peptides
      ([Tyr3]-octreotate and [Lys3]-bombesin) and the conjugates radiolabelled with
      copper-64.

PMID- 19587926
TI  - Direct lateral metallation using alkali-metal mediated zincation (AMMZn): SiC-H
      vs.Si-O bond cleavage.
AB  - A new application of zincate [(THF)Li(TMP)(tBu)Zn(tBu)] (1) in alkali-metal
      mediated zincation (AMMZn) is reported by isolating and structurally defining the
      first intermediates of direct lateral zincation (DlZn) of
      trimethyl(phenoxy)silane (2) both of which adopt novel six-element {ZnCSiOLiN}
      ring structures.

PMID- 19587924
TI  - Sensitive and efficient detection of thrombus with fibrin-specific manganese
      nanocolloids.
AB  - In this work, we report novel fibrin targeted "soft-type" manganese-based
      contrast agents for MRI with the potential to noninvasively image intravascular
      thrombus which could warrant aggressive medical intervention to preclude
      subsequent myocardial infarction or stroke.

PMID- 19587927
TI  - Controlled catch and release of small molecules with cucurbit[6]uril via a
      kinetic trap.
AB  - For the first time a lid-free and charge-free inclusion complex with
      cucurbit[6]uril (CB[6]) has been isolated, the crystal structure is reported and
      the robust nature of the complex is demonstrated in the solid state while facile
      controlled release of the guest is achieved in solution.

PMID- 19587928
TI  - Palladium-catalyzed amidation-hydrolysis reaction of gem-dihaloolefins: efficient
      synthesis of homologated carboxamides from ketones.
AB  - A simple and efficient palladium-catalyzed amidation-hydrolysis reaction has been
      developed to afford N-aryl monosubstituted carboxamides in good to excellent
      yields from easily accessible ketone-derived gem-dihaloolefins and aryl amines.

PMID- 19587929
TI  - Oxindole synthesis by direct C-H, Ar-H coupling.
AB  - A novel copper(II)-mediated route for the conversion of anilides into 3,3
      disubstituted-oxindoles is described which proceeds via a formal C-H, Ar-H
      coupling process.

PMID- 19587931
TI  - Competition between cleavage and decarboxylation in photolysis of alpha-carboxy-2
      nitrobenzyl protected cysteine derivatives.
AB  - Photolysis of model peptides containing alpha-carboxy-2-nitrobenzyl (CNB) or
      alpha-carboxy-4,5-dimethoxy-2-nitrobenzyl (CDMNB) protected cysteines in aqueous
      solution gives the expected 2-nitrobenzyl-type photocleavage and can be
      accompanied by photodecarboxylation depending on structural aspects.

PMID- 19587930
TI  - The first enantioselective synthesis of palinurin.
AB  - The first enantioselective synthesis of palinurin has been accomplished starting
      from commercially available furaldehyde and (R)-methyl-3-hydroxy-2
      methylpropionate; the key steps of the synthesis include the use of a chiral
      pyrrolidine to create the chiral tetronic moiety, and Horner-Wadsworth-Emmons,
      Wittig and Wittig-Horner reactions to construct the alkene units.

PMID- 19587932
TI  - Supported silver nanoparticle catalyst for selective hydration of nitriles to
      amides in water.
AB  - Hydroxyapatite-supported silver nanoparticles (AgHAP) acted as a highly efficient
      reusable heterogeneous catalyst for hydration of diverse nitriles, including
      heteroaromatic ones, into amides in water.

PMID- 19587933
TI  - Direct aldol reactions catalyzed by intramolecularly folded prolinamide dendrons:
      dendrimer effects on stereoselectivity.
AB  - Dendritic effects on both the enantioselectivity and diastereoselectivity of the
      direct aldol reaction were observed for pyridine-2,6-dicarboxamide dendrons
      terminated with L-prolinamides.

PMID- 19587934
TI  - Iron-catalyzed cross-aldol reactions of ortho-diketones and methyl ketones.
AB  - Iron-catalyzed cross-aldol reactions of ortho-diketones and methyl ketones were
      developed and the thus formed aldol products were efficiently transformed into
      cyclohepta-2,4,6-trienone derivatives (tropones) under thermal conditions via
      ring-expansion.

PMID- 19587935
TI  - Boron-enriched star-shaped molecule via cycloaddition reaction.
AB  - The facile synthesis of a thermally stable carborane appended symmetrical star
      shaped molecule having six bulky o-carborane clusters on the periphery, thereby
      containing sixty boron atoms was accomplished via a cobalt-catalyzed [2+2+2]
      cycloaddition reaction.

PMID- 19587936
TI  - Experimental realization of catalytic CH4 hydroxylation predicted for an iridium
      NNC pincer complex, demonstrating thermal, protic, and oxidant stability.
AB  - A discrete, air, protic, and thermally stable (NNC)Ir(III) pincer complex was
      synthesized that catalytically activates the CH bond of methane in
      trifluoroacetic acid; functionalization using NaIO4 and KIO3 gives the oxy-ester.

PMID- 19587937
TI  - Electrochemical preparation of silicon nanowires from nanometre silica in molten
      calcium chloride.
AB  - Here we report Si nanowire growth by electrochemical reduction of nanometre
      silica in molten CaCl2; to our knowledge, this is the first report of an
      electrochemical route that provides crystalline Si nanowires in large quantities.

PMID- 19587938
TI  - Fast, copper-free click chemistry: a convenient solid-phase approach to
      oligonucleotide conjugation.
AB  - Solid-phase oligonucleotide conjugation by nitrile oxide-alkyne click
      cycloaddition chemistry has been successfully demonstrated; the reaction,
      compatible with all nucleobases, requires no metal catalyst and proceeds under
      physiological conditions.

PMID- 19587939
TI  - Metal complexes with two different hydrogen-bond donor ligands as anion hosts.
AB  - The replacement of one pyrazole ligand by 2-aminopyridine in previously known
      rhenium tricarbonyl pyrazole complexes leads to more selective anion hosts.

PMID- 19587940
TI  - Direct synthesis of hierarchical zeolite from a natural layered material.
AB  - Hierarchical SAPO-34 zeolite with high crystallinity and excellent hydrothermal
      stability was directly synthesized in the nanoscale confined environment provided
      by the natural layered material kaolin.

PMID- 19587941
TI  - Asymmetric Friedel-Crafts reaction of N-heterocycles and nitroalkenes catalyzed
      by imidazoline-aminophenol-Cu complex.
AB  - Catalytic asymmetric Friedel-Crafts reaction of pyrrole with nitroalkenes was
      smoothly catalyzed by newly synthesized nitro-substituted imidazoline-aminophenol
      (1b)-Cu complex to give the adduct with up to 92% ee.

PMID- 19587942
TI  - Chiral iron complex catalyzed enantioselective oxidation of racemic benzoins.
AB  - An efficient, economic and environmentally friendly enantioselective oxidation of
      racemic benzoins (alpha-hydroxy ketones) catalyzed by a chiral iron complex has
      been developed using molecular oxygen as a terminal oxidant with good selectivity
      and excellent enantiomeric excess.

PMID- 19587943
TI  - The rhodium carbene route to oxazoles: a remarkable catalyst effect.
AB  - Dirhodium tetraacetate catalysed reaction of alpha-diazo-beta-keto-carboxylates
      and -phosphonates with arenecarboxamides gives 2-aryloxazole-4-carboxylates and 4
      phosphonates by carbene N-H insertion and cyclodehydration; in stark contrast,
      dirhodium tetrakis(heptafluorobutyramide) catalysis results in a dramatic change
      of regioselectivity to give oxazole-5-carboxylates and 5-phosphonates.

PMID- 19587948
TI  - The master of chemical topology.

PMID- 19587949
TI  - Active metal template synthesis of rotaxanes, catenanes and molecular shuttles.
AB  - Active metal template synthesis is a powerful new strategy for the construction
      of rotaxanes, catenanes and other mechanically interlocked molecular structures.
      The key feature is that the metal plays a dual role during the assembly of the
      interlocked architecture, acting as both a template for entwining or threading
      the components and as a catalyst for capturing the interlocked final product by
      covalent bond formation. Unlike traditional "passive" metal template methods to
      rotaxanes and catenanes, permanent recognition motifs are not required on each of
      the components to be interlocked (i.e., the assembly can be traceless) and the
      template can often be used in sub-stoichiometric quantities. Since its inception
      in 2006, a rapidly growing number of different metal-catalysed reactions have
      proven suitable for the active metal template synthesis of both rotaxanes and
      catenanes, including the copper(i)-catalysed terminal alkyne-azide cycloaddition
      (the CuAAC "click" reaction), palladium- and copper-catalysed alkyne
      homocouplings and heterocouplings, and palladium-catalysed oxidative Heck
      couplings and Michael additions. In addition to simple rotaxanes and catenanes,
      the synthetic strategy has been used to construct switchable molecular shuttles
      with weak intercomponent interactions (a requirement for fast shuttling) and to
      provide insight into the mechanisms of transition metal-catalysed reactions. In
      this tutorial review we highlight the utility and potential of the early examples
      of the active metal template strategy in mechanically interlocked molecule
      synthesis.

PMID- 19587950
TI  - Light powered molecular machines.
AB  - The bottom-up construction and operation of mechanical machines of molecular size
      is a topic of high interest for nanoscience, and a fascinating challenge of
      nanotechnology. Like their macroscopic counterparts, nanoscale machines need
      energy to operate. Although most molecular motors of the biological world are
      fueled by chemical reactions, light is a very good choice to power artificial
      molecular machines because it can also be used to monitor the state of the
      machine, and makes it possible to obtain systems that show autonomous operation
      and do not generate waste products. By adopting an incrementally staged design
      strategy, photoinduced processes can be engineered within multicomponent
      (supramolecular) species with the purpose of obtaining light-powered molecular
      machines. Such an approach is illustrated in this tutorial review by describing
      some examples based on rotaxanes investigated in our laboratories.

PMID- 19587951
TI  - Prototypes of molecular motors based on star-shaped organometallic ruthenium
      complexes.
AB  - This tutorial review presents our strategy to control the rotation in a molecular
      rotary motor, and the family of star-shaped ruthenium complexes designed to
      perform such a task. The molecules have a piano-stool structure with a "stator"
      meant to be grafted on a surface, and a "rotor" bearing redox-active groups, so
      that addressing the molecule with nano-electrodes would trigger rotation.

PMID- 19587952
TI  - Topology in molecules inspired, seen and represented.
AB  - The way in which molecules are imagined and subsequently represented in drawings
      or models is a fundamental part of the chemist's activity. In this tutorial
      review we shall discuss these doings for molecules which contain an element of
      entanglement and whose structural representation on a plane requires the presence
      of crossing points. The review provides a personal view of finding inspiration,
      how to draw and understand topologically complex molecules, and the way they can
      be "switched". The review compares and contrasts approaches to illustration and
      conception of catenanes and knots and the dynamic processes taking place within
      them, and discusses the graphic tools used to portray them.

PMID- 19587953
TI  - Molecular recognition of pertechnetate and perrhenate.
AB  - This tutorial review covers the chemistry of artificial receptors designed to
      recognize the pertechnetate and perrhenate anions. It focuses on the molecular
      features that give rise to effective and selective complexation. Specific
      receptor classes are discussed in the context of available solution-phase and
      solid-state data with differences between pertechnetate and perrhenate binding
      behavior being highlighted where appropriate.

PMID- 19587954
TI  - Fullerene for organic electronics.
AB  - This tutorial review surveys and highlights the integration of different
      molecular wires-in combination with chromophores that exhibit (i) significant
      absorption cross section throughout the visible part of the solar spectrum and
      (ii) good electron donating power-into novel electron donor-acceptor conjugates.
      The focus is predominantly on charge transfer and charge transport features of
      the most promising systems.

PMID- 19587955
TI  - Nickel-catalysed Negishi cross-coupling reactions: scope and mechanisms.
AB  - The Negishi cross-coupling of organozinc reagents is a valuable tool for the
      formation of C-C bonds in the presence of functional groups. Although this
      reaction is catalysed by Ni or Pd complexes, the latter have been much more
      developed. Nevertheless, Ni derivatives have become important in recent years,
      especially for their activity in the formation of alkyl-alkyl bonds. The
      mechanisms involved in Ni-catalysed reactions are different from the usual
      catalytic cycle involving oxidative addition-transmetalation-reductive
      elimination that is generally accepted for Pd-catalysed reactions. This tutorial
      review presents the more recent advances in Ni-catalysed Negishi cross-couplings
      for the formation of different kinds of C-C bonds and discusses their proposed
      reaction mechanisms.

PMID- 19587956
TI  - Base-pairing mediated non-covalent polymers.
AB  - The naturally occurring nucleic acid bases (nucleobases) adenine, thymine
      (uracil), guanine, and cytosine are widely appreciated for their ability to
      stabilize canonical Watson-Crick base-pairing motifs, as well as a number of
      other well-characterized arrangements, such as Hoogsteen and wobble heterodimers,
      and a variety of homodimers. In this tutorial review, the use of these kinds of
      interactions to form synthetic polymeric and oligomeric ensembles is summarized.
      Particular emphasis will be placed on synthetic analogues of guanine that
      stabilize the formation of well-defined higher order aggregates, as well as de
      novo polymeric systems whose properties are modulated by the presence of
      nucleobase derivatives incorporated within or attached to the chain-defining
      backbone. In both cases, nucleobase-nucleobase interactions serve to underlie the
      chemistry, establish the structural morphology, and enable the development of
      bioinspired, environmentally responsive materials.

PMID- 19587957
TI  - Luminescent ruthenium-polypyridine complexes & phosphorus ligands: anything but a
      simple story.
AB  - This tutorial review presents an exhaustive picture of the luminescence studies
      that have been undertaken on ruthenium(ii) complexes bearing polypyridine and
      phosphorus(iii) ligands. The introduction of phosphorus to the Ru coordination
      sphere has multiple consequences on the nature and energy of the various excited
      states involved, but it does not necessarily rule out room temperature emission.

PMID- 19587958
TI  - Photoactive corrole-based arrays.
AB  - The collection and conversion of light energy into chemical energy is based on
      the use of molecular structures of various complexity, where the absorbed light
      energy is first converted into an excited state able to undergo energy or
      electron transfer processes and finally it is stored in a charge separated state
      as chemical (electrochemical) potential. A bio-mimetic approach has seen
      tetrapyrroles number among the most common components of these arrays. This
      tutorial review reports on the use of relatively new tetrapyrroles, corroles, in
      this field. A brief presentation of the electrochemical and photophysical
      properties of the corrole units relevant to the application is presented together
      with a discussion on the photo- and thermal stability issues, followed by an
      overview of the activity and improvements in the preparation of photo-active
      molecular arrays containing corroles.

PMID- 19587960
TI  - The ins and outs of proton complexation.
AB  - Proton complexation differs from simple protonation by the fact that the
      coordinated hydrogen atom is bound intramolecularly to more than one donor atom.
      This is usually achieved by covalent bonding supplemented by hydrogen bonding. In
      a few cases, however, the complexed proton is hydrogen-bound to all donor atoms,
      which gives rise to single well (SWHB) and low barrier (LBHB) hydrogen bonds.
      This tutorial review highlights a full range of proton complexes formed with
      chelating and "proton-sponge"-type ligands, cryptand-like macropolycycles, and
      molecules of topological relevance, such as rotaxanes and catenanes. The concept
      of proton complexation can explain how the smallest cation possible can bring
      molecules to order and trigger intramolecular molecular rearrangements and
      motions.

PMID- 19587961
TI  - Catenanes and threaded systems: from solution to surfaces.
AB  - Functional catenanes and threaded systems able to perform controllable mechanical
      motions are ideally suited for the design of molecular devices displaying
      mechanical, electronic, information or sensing functions. These systems have been
      extensively studied in solution phase and numerous examples of stimuli-driven
      molecular shuttles have been reported. However, for fully developing their
      potential applications, they must be interfaced with the macroscopic world. To
      achieve this objective, in the last few years catenanes and rotaxanes have been
      organized over surfaces in the form of chemisorbed monolayers or physisorbed
      monolayers, multilayers and thin films. This tutorial review summarizes the
      different techniques for the deposition on surfaces and characterization of
      switchable catenanes and rotaxanes, and highlights the properties of these new
      functional surfaces and their potential applications.

PMID- 19587959
TI  - Modern reaction-based indicator systems.
AB  - Traditional analyte-specific synthetic receptors or sensors have been developed
      on the basis of supramolecular interactions (e.g., hydrogen bonding,
      electrostatics, weak coordinative bonds). Unfortunately, this approach is often
      subject to limitations. As a result, increasing attention within the chemical
      sensor community is turning to the use of analyte-specific molecular indicators,
      wherein substrate-triggered reactions are used to signal the presence of a given
      analyte. This tutorial review highlights recent reaction-based indicator systems
      that have been used to detect selected anions, cations, reactive oxygen species,
      and neutral substrates.

PMID- 19587962
TI  - 1,10-phenanthrolines: versatile building blocks for luminescent molecules,
      materials and metal complexes.
AB  - 1,10-phenanthroline entails several appealing structural and chemical properties:
      rigidity, planarity, aromaticity, basicity, chelating capability. This makes it a
      versatile starting material for synthetic organic, inorganic and supramolecular
      chemistry. In this tutorial review we examine how the chemical versatility of
      pristine 1,10-phenanthroline, a weakly fluorescent molecule, has been exploited
      to design many UV-Vis-NIR luminescent organic derivatives and coordination
      compounds with transition-metal (Ru(ii), Os(ii), Rh(iii), Cr(iii), Pt(ii),
      Zn(ii), Cu(i), Ag(i)) and rare-earth (Eu(iii),Tb(iii), Yb(iii), Nd(iii), Er(iii))
      cations. They are utilized for many analytical and technological applications.

PMID- 19587963
TI  - Sulfate anion templation of macrocycles, capsules, interpenetrated and
      interlocked structures.
AB  - This tutorial review examines the potential of anions, in particular sulfate, to
      template the formation of complex molecular architectures. Until recently,
      sulfate has been largely overlooked in this area and the examples described
      herein demonstrate this anion's versatility in templating the formation of a
      diverse range of molecular systems including macrocycles, helixes, molecular
      capsules, interpenetrated and interlocked assemblies such as catenanes. In
      addition sulfate has been shown to template the formation of interpenetrated
      structures on a range of surfaces including gold, polystyrene beads and silicate
      nanoparticles, highlighting the potential of this anion in the fabrication of
      functional sensory devices exhibiting highly selective binding behaviour.

PMID- 19587964
TI  - Engineering discrete stacks of aromatic molecules.
AB  - Intrigued by transannular interactions occurring in stacked aromatic molecules,
      chemists have long endeavored to engineer discrete stacks of specific lengths and
      orientation. The maturation of self-assembly methodologies has shifted the focus
      away from utilizing covalent scaffolds to harnessing non-covalent interactions
      such as ionic interactions, hydrogen bonds, metal-ligand interactions, and
      aromatic interactions. Aromatic molecules often assemble into ill-defined,
      infinite aggregates and thus multiple self-assembly techniques must be combined
      to achieve the desired stack size and conformations. This critical review briefly
      highlights covalent scaffolds of stack aromatics before focusing on modern self
      assembly based strategies for engineering discrete stacks of aromatic molecules
      (149 references).

PMID- 19587965
TI  - Recent advances in the development of aryl-based foldamers.
AB  - In recent years, significant effort has gone into making synthetic oligomers that
      can attain well-defined conformations analogous to the folding of biomolecules.
      The diversity of the structural building blocks ranges from peptidic and other
      aliphatic repeat units to aromatic ones, which do not have a natural counterpart.
      In this critical review, we will focus on the developments in aromatic foldamers
      in the last two years and their potential applications. This review will be of
      interest to people working on the structural and functional mimicry of
      biomolecules and will, we hope, stimulate further research into novel
      applications (149 references).

PMID- 19587966
TI  - Phosphines as building blocks in coordination-based self-assembly.
AB  - Although phosphines have been less widely investigated in coordination self
      assembly than have N- and O-donor ligands, interesting and unusual chemistry has
      been observed from their study in this context. This includes the selective
      formation of large rings, unsaturated as well as complete coordination cages,
      solvent- and anion-dependent aggregation, in addition to ring-opening
      polymerisation to give crystalline or non-crystalline coordination polymers.
      Important aspects which underpin this chemistry include (i) soft donor character,
      (ii) pyramidal geometry at the donor atom, (iii) highly bulky and irregular
      shapes, (iv) the applicability of (31)P NMR spectroscopy, and (v) their relevance
      to organometallic chemistry and homogeneous catalysis. In this critical review,
      findings which precede the concept of self-assembly as adopted by synthetic
      chemists as well as the latest 'supramolecular' chemistry of phosphines are
      discussed together in an attempt to give the current state of the topic in its
      historical context. Finally, some aspects and opportunities which may be of
      interest in the future are suggested (107 references).

PMID- 19587967
TI  - Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies
      and toxicity.
AB  - This critical review provides an overall survey of the basic concepts and up-to
      date literature results concerning the very promising use of gold nanoparticles
      (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and
      conjugation with biological and biocompatible ligands, plasmon-based labeling and
      imaging, optical and electrochemical sensing, diagnostics, therapy (drug
      vectorization and DNA/gene delivery) for various diseases, in particular cancer
      (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the
      essential in vitro and in vivo toxicity. It will interest the medicine,
      chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities
      (211 references).

PMID- 19587968
TI  - The coordination chemistry of dipyridylbenzene: N-deficient terpyridine or
      panacea for brightly luminescent metal complexes?
AB  - 1,3-Di(2-pyridyl)benzene (dpybH) structurally resembles the widely-used ligand
      terpyridine (tpy), with which it is isoelectronic. In this critical review,
      following a brief overview of synthetic strategies for dpybH and derivatives, we
      survey the different types of complex that are possible with these ligands.
      Whilst metals such as ruthenium(ii), osmium(ii) and platinum(ii) give a
      terdentate N--C--N binding mode in which cyclometallation occurs at C(2), the
      ions iridium(iii), rhodium(iii) and palladium(ii) favour C(4) metallation. The
      latter process can be blocked by appropriate ligand modification, to allow the N-
      C--N mode to be accessed with these metal ions too. The luminescence properties
      of the complexes are discussed. A huge range of emission efficiencies are
      encountered amongst Ir(iii) complexes containing dpyb derivatives, according to
      the other ligands present. Trends can be rationalised with the aid of simple
      frontier-orbital considerations. The Pt(ii) complexes of dipyridylbenzenes are
      also intensely luminescent. Their application to contemporary organic light
      emitting device (OLED) technology is discussed, including white light emitters
      exploiting excimer emission. Their potential as cell imaging agents amenable to
      time-resolved detection procedures on the microsecond timescale has also been
      demonstrated (118 references).

PMID- 19587969
TI  - The chemistry of the mechanical bond.
AB  - The use of templation in the synthesis of unnatural products where two or more
      components are mechanically interlocked has not only raised the efficiency of
      their production to near quantitative levels in some instances, but the molecular
      recognition that aids and abets the templation is also part and parcel of the
      molecules after they have been prepared, purified and presented for
      investigation. The fact that the molecular recognition 'lives on' in mechanically
      interlocked molecules, following their templated formation, makes them prime
      candidates for applications that straddle the scientific and technical worlds
      from devices that could spawn new information technologies to integrated systems
      that could have fundamental applications in the health-care industries. The
      challenge to make more and more sophisticated compounds is predicated upon our
      fundamental understanding of the nature of the mechanical bond and how this
      associated knowledge base can be employed to do complex systems chemistry in very
      different environments where emergent phenomena become the order of the day
      (critical review, 104 references).

PMID- 19587982
TI  - Metal-binding mechanisms in metallothioneins.
AB  - Metallothionein are small, cysteine-rich, metal-binding proteins that are found
      ubiquitously in nature. Most metallothioneins bind multiple metals in two well
      defined metal-thiolate clusters. This perspective discusses the use of optical
      spectroscopy to study the metalation of metallothioneins and the emergence of
      electrospray ionization mass spectrometry as a means of studying the mechanism of
      metalation for metallothioneins. A brief history of past kinetic studies of
      cadmium metallothioneins and recent kinetic study advances for the arsenic
      metalation of metallothionein will be presented. Lastly, a possible functional
      role for the two-domain structure of metallothionein will be briefly discussed.

PMID- 19587983
TI  - Nitrene transfer reactions mediated by metallo-porphyrin complexes.
AB  - Nitrene transfer reactions represent a useful methodology to synthesize in a few
      steps high added-value compounds used as organic intermediates. Herein, we
      describe the catalytic activity of metal porphyrin complexes in a wide range of
      reactions such as C-H hydrocarbon amination and olefin aziridination to
      synthesize nitrogen containing molecules. All the most important nitrene sources
      have been reviewed stressing the potentiality and limits of each one in the
      particular class of chemical transformation.

PMID- 19587984
TI  - N-Aryl substituted heterocyclic silylenes.
AB  - Two N-aryl substituted five-membered heterocyclic silylenes and their nickel
      complexes have been isolated and structurally characterized.

PMID- 19587985
TI  - Control of reversible ligand insertion via supramolecular interactions in the
      solid state.
AB  - Reversible insertion of a ligand molecule into the coordination sphere of a metal
      complex in the solid state by variation of associated supramolecular hydrogen
      bonding interactions in the solid is demonstrated in studies of complexes of
      copper(I) nitrate with thiourea.

PMID- 19587986
TI  - Titanocene as a precursor for a cyclopentadienyl-free titanium(III)-manganese(II)
      cluster: a new approach for nano-size materials.
AB  - A simple and unique route to access the heterometallic cluster [Mn4Ti4(micro
      Cl)2(micro3,eta2-L)2(micro,eta2-L)10Cl6] (1) with two Mn2Ti2 butterfly core
      motifs is reported. This method comprises elimination of the Cp ring from
      Cp2TiCl2 as CpH in the presence of metallic Mn in 2-methoxoethanol (LH) as a
      proton source. Complex 1 belongs to a group of magnetic clusters, which consists
      of two weakly interacting M4 subunits.

PMID- 19587987
TI  - The role of the Pb2+ 6s lone pair in the structure of the double perovskite
      Pb2ScSbO6.
AB  - The new double perovskite Pb2ScSbO6 was synthesized by standard ceramic
      procedures; the Rietveld refinement of room temperature neutron powder
      diffraction data shows that the crystal structure is well defined in the space
      group Fm3[combining macron]m. It contains a completely ordered array of
      alternating ScO6 and SbO6 octahedra sharing corners; the PbO12 polyhedra present
      an off-center displacement of the lead atoms along the [111] direction, due to
      the electrostatic repulsion between the Pb2+ 6s lone pair and the Pb-O bonds of
      the cuboctahedron. Dielectric permittivity measurements show a peak near 343 K,
      with a Curie-Weiss response above this temperature, which suggests an
      antiferroelectric behavior. Finally we present a DFT study of the electronic
      structure of Pb2ScSbO6, showing a great difference between the electronic density
      within SbO6 and ScO6 octahedra.

PMID- 19587988
TI  - Epoxidation of olefins catalysed by vanadium-salan complexes: a theoretical
      mechanistic study.
AB  - Plausible mechanisms of olefin epoxidation catalysed by a V-salan model complex
      [VIV(=O)(L)(H2O)] (1, L=(CH2NHCH2CH=CHO-)2) in the presence of H2O2 are
      investigated and compared by theoretical methods using density functional theory.
      Three main routes, i.e. the Mimoun, Sharpless and biradical mechanisms, were
      examined in detail, and the Sharpless pathway was found to be the most favourable
      one. The reaction starts from the formation of an active catalytic species
      [VV(=O)(OO)(LH)] (3c) upon interaction of 1 with H2O2, then concerted, highly
      synchronous attack of the olefin to 3c occurs yielding the epoxide and catalyst
      [VV(=O)2(LH)], the latter being oxidized by H2O2 to 3c. The activation barrier
      strongly depends on the proton location in the catalyst molecule and is the
      lowest when one of the oxygen atoms of the salan ligand is protonated and the
      vanadium atom is penta-coordinated with one vacant coordination position (complex
      3c). The olefin in this reaction acts as an electron donor (nucleophile) rather
      than as an electron acceptor (electrophile).

PMID- 19587989
TI  - Reaction of hydrogen peroxide with coordinated superoxide in [(NH3)5CoIII(micro
      O2)CoIII(NH3)5]5+: a mechanistic study.
AB  - In aqueous acetate buffer media, hydrogen peroxide reduces the bridging
      superoxide in [(NH3)5CoIII(micro-O2)CoIII(NH3)5]5+ (1) to the corresponding
      peroxide in the complex, [(NH3)5CoIII(micro-O2H)CoIII(NH2)(NH3)4]4+ (2), itself
      being oxidized to HO2*. The complex 2 thus produced decomposes rapidly to the
      final products, CoII, NH3, etc. instead of reacting with a second molecule of
      hydrogen peroxide. In the presence of excess [H2O2] over (1), the reaction obeyed
      first-order kinetics and exhibited inverse proton dependence. [(NH3)5CoIII(micro
      O2)CoIII((NH2)(NH3)4]4+ (3), a conjugate base of 1, seems to be the kinetically
      reactive species and the cause for the observed inverse proton dependence.
      Kinetics is little affected when one of the hydrogen atoms from hydrogen peroxide
      is replaced with an alkyl group, as in tert-butyl hydroperoxide. But replacement
      of both the H atoms with alkyl groups halts the reaction as seen with di-tert
      butyl peroxides, and peroxodisulfate ion. The reaction rate with hydrogen
      peroxide significantly decreases with increasing proportion of D2O replacing
      water in the solvent and the rate-limiting step seems to be an H-atom transfer.

PMID- 19587990
TI  - Sol-gel analogous aminolysis-ammonolysis of chlorosilanes to chlorine-free
      Si/(C)/N-materials.
AB  - Large amounts of chlorosilanes, especially SiCl4 and CH3SiCl3, are produced as
      side-products of the industrial fabrication of solar or electronic grade silicon
      and the Muller-Rochow process. It was a goal of the present study to transform
      these compounds into useful chlorine-free precursors for Si/(C)/N ceramics via a
      sol-gel analogous liquid processing route. Chlorine substitution of the
      chlorosilanes (mixtures) with diethylamine did not yield chlorine-free products,
      complete reactions are only possible with lithium diethylamide. However,
      aminolyses with n-propylamine were successful. Transamination with ammonia was
      not possible with diethylaminosilanes but was with n-propylaminosilanes in
      various solvents. This result was attributed to steric reasons and polar
      interactions of the N-H groups. Colourless solid or liquid polysilazanes were
      obtained, depending on the silane (mixture) and the solvent. Transamination
      reactions of CH3Si(NH-n-Pr)3 in chloroform reproducibly yielded a cage-like
      oligosilazane of the composition (CH3)9Si9(NH)12N. Single crystal X-ray structure
      analysis revealed a seven-cyclic cluster containing four six- and three ten
      membered silazane rings. This unique silazane cage as well as the other
      aminosilanes and the silazanes were comprehensively characterised using multi
      nuclear solid state and solution NMR, elemental analyses and thermal gravimetry
      (TGA).

PMID- 19587991
TI  - Gold(I) complexes of cyclodiphosphazanes cis-{RP(micro-NtBu)}2: structure of a
      novel tetranuclear gold(I) macrocycle, [{Au{(o-MeOC6H4O)P(micro
      NtBu)}2}4](ClO4)4.
AB  - Reactions of two equivalents of [AuCl(SMe2)] with cyclodiphosphazanes cis
      {RP(micro-NtBu)}2 (1a-1d) produce binuclear gold(I) complexes of the type,
      [ClAu{RP(micro-NtBu)}2AuCl] (2 R=OC6H4OMe-o, 3R=OCH2CH2OMe, 4R=NEt2, 5R=NHtBu) in
      quantitative yield. A similar reaction between cis-{(o-MeOC6H4O)P(micro-NtBu)}2
      (1a) and [AuCl(SMe2)] in a 1:1 molar ratio afforded the mono-nuclear complex
      [ClAu{(o-MeOC6H4O)P(micro-NtBu)}2] (6). Addition of two equivalents of CuX (X=Br,
      I) to the chloro derivative 2 leads to the formation of bromo, [BrAu{(o
      MeOC6H4O)P(micro-NtBu)}2AuBr] (7), and iodo, [IAu{(o-MeOC6H4O)P(micro-NtBu)}2AuI]
      (8), derivatives through halogen exchange reactions. A tetranuclear gold(I)
      macrocycle [Au{(o-MeOC6H4O)P(micro-NtBu)}2]4(ClO4)4 (9) and a mononuclear gold(I)
      complex [Au({(o-MeOC6H4O)P(micro-NtBu)}2)2]ClO4 (10) were obtained, respectively,
      from 1:1 and 2:1 stoichiometric reactions between 1a and [Au(SMe2)2]ClO4.
      Molecular structures of complexes 4, 6, 7, 8 and 9 are confirmed by single
      crystal X-ray diffraction studies. Interestingly, the crystal structure of the
      tetra-nuclear AuI macrocycle 9 reveals the encapsulation of one ClO4- anion
      inside the bowl shaped macrocyclic cavity through weak Au...O and C-H...O
      interactions.

PMID- 19587992
TI  - Aerosol assisted chemical vapour deposition of Cu-ZnO composite from single
      source precursors.
AB  - Two heterobimetallic precursors [Zn(TFA)3(micro-OH)Cu3(dmae)3Cl].THF (1) and
      [Zn(TFA)4Cu3(dmae)4] (2) [dmae=N,N-dimethylaminoethanolate and
      TFA=trifluoroacetate], have been synthesized and characterized by their melting
      points, elemental analysis, FT-IR spectroscopy, mass spectrometry, TGA and single
      crystal X-ray diffraction methods. Both complexes were used to deposit thin films
      of Cu-ZnO composite on glass substrates by aerosol assisted chemical vapor
      deposition (AACVD) method. The films were characterized by "scotch tape" test for
      adhesion, thickness measurement as a function of temperature, EDX for
      composition, SEM for surface morphology and XRD for crystalline phases. Thin film
      deposition studies at 250, 325, 400, 475 degrees C indicated the increase in
      thickness with temperature reaching a maximum at 400 degrees C and then
      decreasing. EDX and PXRD results showed the uniform distribution of cubic
      metallic copper and hexagonal zinc oxide phases which make them useful for
      nanocatalysis on structured surfaces.

PMID- 19587993
TI  - 1H-NMR studies on the ternary complexes of rare-earth ions with
      thenoyltrifluoroacetone and polyethers in dichloromethane.
AB  - The structures of the ternary complexes of lanthanoid and yttrium (Ln3+)
      thenoyltrifluoroacetonates (tta-) with polyether (POE) in organic phase were
      investigated by 1H-NMR spectroscopy, where the POEs are crown ethers (18-crown-6
      and benzo-18-crown-6) and monodispersed linear polyethers (DEOn: HO-(CH2CH2O
      )nC12H25, where n=4, 6, 8). The changes in chemical shift of methylene protons of
      POE by addition of the adduct complex [Ln(tta)3(POE)] were measured at various
      Ln3+-to-POE concentration ratios. Chemical shift changes for each proton of POE
      by the formation of [Ln(tta)3(POE)] were determined. Results revealed that oxygen
      atoms at the hydroxyl terminal of linear POE have higher tendency to coordinate
      to the metal ion in [Ln(tta)3] complex. Three (for La3+) or two (for Lu3+ or Y3+)
      oxygen atoms of the POE coordinate to the metal ion without substitution of tta-
      ligands to satisfy the metal ion's coordination number of nine or eight,
      respectively. In the case of 18-membered crown ether complexes, La3+ is
      incorporated inside the cavity of the POE, displacing one of the three tta- from
      the inner coordination sphere while the other two remain coordinated to the metal
      ion. On the other hand, for the adduct of Y3+ complex with crown ether, all three
      tta- ligands are directly coordinating to the metal ion.

PMID- 19587994
TI  - Synthesis and structure of dinuclear hafnium(IV) and zirconium(IV) complexes
      sandwiched between 2 mono-lacunary alpha-Keggin polyoxometalates.
AB  - The synthesis and characterization of two dinuclear HfIV and ZrIV complexes
      sandwiched between 2 mono-lacunary alpha-Keggin polyoxometalates (POMs), i.e.,
      (Et2NH2)8[{alpha-PW11O39Hf(micro-OH)(H2O)}2].7H2O (Et2NH(2)-1) and
      (Et2NH2)8[{alpha-PW11O39Zr(micro-OH)(H2O)}2].7H2O (Et2NH(2)-2), are described.
      [Note: the moieties of their polyoxoanions are abbreviated simply as and ,
      respectively.] A pair of HfIV- and ZrIV-containing POMs belonging to the same
      family were herein isolated as diethylammonium salts and were unambiguously
      characterized by complete elemental analysis, including sodium and oxygen
      analyses, TG/DTA, FT-IR, single-crystal X-ray structure analysis and solution
      (31P and 183W) NMR spectroscopy. Polyoxoanions 1 and 2 were isostructural with
      each other. The central [M2(micro-OH)2(H2O)2]6+ (M=Hf, Zr) cation unit was
      composed of 2 edge-sharing polyhedral M units, which were linked through 2 micro
      OH groups and contained 1 water molecule coordinated to each metal center. Since
      the mono-lacunary Keggin POM acts as an oxygen-donor quadridentate ligand, the Hf
      and Zr centers are 7-coordinate. It should be noted that the present 2 Keggin 2:2
      type compounds, Et2NH(2)-1 and Et2NH(2)-2, undergo a reversible conversion to
      Keggin 1:2-type complexes [M(alpha-PW11O39)2]10-, respectively, in solution under
      appropriate conditions. The synthesis of Et2NH(2)-1 and Et2NH(2)-2 is based on
      such an interconversion. The Zr compound Et2NH(2)-2 was rigorously compared with
      the 3 Zr POMs (OK-1-OK-3), recently reported by Kholdeeva's group: their POMs in
      a different protonation-state did not contain any coordinating water molecules.

PMID- 19587995
TI  - Aggregation in methanol and formation of molecular glasses for europium(III) N
      acylaminocarboxylates: effects of alkyl chain length and head group.
AB  - Europium(III) complexes of N-acyl-DL-alaninates (acyl=acetyl, butanoyl, hexanoyl,
      octanoyl, decanoyl, dodecanoyl and tetradecanoyl), N-octanoyl-DL-phenylalaninate,
      and N-octanoyl-L-serinate were prepared to understand the effects of alkyl chain
      length and the type of head group on the formation of glassy states and on the
      aggregation behaviour in solutions. The acylalaninate complexes had a tendency to
      form a transparent glass, whereas Eu(ala)3 (ala=DL-alaninate) was easily
      crystallized. Of the C2(acetyl)-C14(tetradecanoyl) chains in the ligands, the C4
      C8 chains were the most favourable to assume a stable glassy state by solvent
      vaporization. The europium(III) complexes having an acyl chain of C6 (hexanoyl)
      or longer exhibited a peak below 2theta=5 degrees due to the presence of a
      bilayer structure in the glassy state. The octanoylserinate complex easily formed
      an anisotropic glass by a solvent-cast method, while the octanoylphenylalaninate
      complex transformed from a transparent glass to an anisotropic glass by an
      annealing treatment. The trend of glass formation was related with the
      aggregation behaviour of the complexes in methanol detected by self-diffusion and
      luminescence properties.

PMID- 19587996
TI  - An NMR study on nickel binding sites in Cap43 protein fragments.
AB  - NMR spectroscopy was used to study the interaction of Ni(II) ions with C-terminal
      sequence of Cap43 protein where, from Thr341 to Gly360 residue, a
      T1R2S3R4S5H6T7S8E9G10 ten-amino acid fragment is consecutively repeated three
      times. The behaviour of ends-blocked Ac-RSRSHTSEG-Am (pept1), Ac-TRSRSHTSEG-Am
      (pept2), and the three repeats Ac-TRSRSHTSEG-TRSRSHTSEG-TRSRSHTSEG-Am (pept3)
      peptides towards Ni(II) ions was examined at different pH values and, for pept3,
      at different ligand-to-metal molar ratios. 1H-1H TOCSY, 1H-13C HSQC, 1H-1H NOESY
      and 1H-1H ROESY multidimensional NMR techniques were performed to understand the
      details of metal binding sites and the conformational behaviour of the peptides.
      The results confirmed that each mono-histidinic sequence of pept3 is able to
      independently coordinate one, two or three Ni(II) ions for 1:1, 1:2 and 1:3
      ligand-to-metal molar ratios, respectively. At higher pH values, the coordination
      of Ni(II) involves imidazole Ndelta of His6 and three preceding deprotonated
      peptide nitrogens from the backbone, giving a {Ndelta, 3N-} chromophore in a
      square planar geometry. In addition, at lower pH values, the involvement of gamma
      O of carboxyl group from Glu9 residue with the formation of a macrochelate giving
      a {Ndelta, gamma-O-, 4O(H2O)} chromophore in an octahedral geometry, was
      evidenced. NMR results allowed us to build a model for the structure of the major
      complex. Structural changes in the conformation of the peptide with organized
      Arg4 and Thr7 side chain orientation promoted by nickel coordination, were
      detected.

PMID- 19587997
TI  - Migration of amide to imine group of lanthanide Schiff base complexes: effect of
      amido group.
AB  - The protonolysis of anionic lanthanide amide complexes (THF)LiLn(NPri2)4 with two
      equiv. of tridentate Schiff base HL (L=3,5-But(2)-2-O-C6H2CH=N-C5H4N) afforded
      the unanticipated products LiL'2Ln(THF) (L'=3,5-But(2)-2-O-C6H2CH(NPri2)-N-C5H4N;
      Ln=Y 1, Sm 2 and Yb 3) formed by intramolecular nucleophilic attack of the amide
      groups at the imine carbon atoms of the original ligand, L. The protonolysis is
      greatly affected by the amide group. When amine elimination was carried out with
      a mixture of Ln[N(TMS)2]3(micro-Cl)Li(THF)3 (TMS=SiMe3) and LiN(TMS)2, the
      expected lanthanide amide complexes with two Schiff base ligands, L2Ln[N(TMS)2]
      (Ln=Sm 4 and Nd 5), were isolated and no migration of the N(TMS)2 group was
      observed because of steric hindrance. Complexes 1-5 were well characterized
      including X-ray structural analyses.

PMID- 19587998
TI  - Cyclic oligomer of oxide clusters through a siloxane bond. Synthesis and
      structure of reaction products of alpha2-mono-lacunary Dawson polyoxometalate
      with tetrachlorosilane and tetraethoxysilane.
AB  - The title compound with the formula (Me2NH2)13H5[{alpha2-P2W17O61(Si2O)}3(micro
      O)3].39H2O Me2NH(2)-1 was obtained in 12.8% (0.258 g scale) yield by a 1:2 molar
      ratio reaction of alpha2-mono-lacunary Dawson polyoxometalate (POM) [alpha2
      P2W17O61]10- with SiCl4 in water and unequivocally characterized by complete
      elemental analysis, TG/DTA, FTIR, (solution and solid-state) 31P NMR, solid-state
      29Si NMR and X-ray crystallography. [Note: the moieties of the polyoxoanions in
      Me2NH(2)-1 and Me2NH(2)-2 are abbreviated simply as 1 and 2, respectively.] X-Ray
      crystallography revealed that the molecular structure of polyoxoanion 1 was a
      cyclic trimer consisting of three alpha2-mono-lacunary Dawson POM subunits
      constituted through intra- and intermolecular siloxane bonds. The compound
      resulted in an approximate Cs symmetry, but not the idealized C3v symmetry,
      because one Dawson unit was unequivalently incorporated into the cyclic
      framework. This compound is the first example of a siloxane-bonding cyclic trimer
      of POMs and its formation suggests that the oxygen atoms in the lacunary site of
      POM are reactive just like the surface oxygen atoms of silica. The formation of
      the cyclic trimer was also clarified by two control experiments: (1) the reaction
      of [alpha2-P2W17O61]10- with Si(OEt)4 under acidic conditions (pH 1), and (2)
      oligomerization under 6 M aqueous HCl acidic conditions (pH approximately 0) of
      the reactive monomer units (RMUs: tentatively assigned as "[alpha2
      P2W17O61{O(SiOH)2}]6-"), derived from the cleavage of Ph-Si bonds by the thermal
      degradation of [alpha2-P2W17O61{O(SiPh)2}]6-. On the other hand, the reactions of
      alpha2-mono-lacunary Dawson POMs with GeX4 (X=OEt, Cl) gave the monomeric species
      of mono-germanium-substituted Dawson POM (Me2NH2)7[alpha2-P2W17O61(GeOH)].5H2O
      Me2NH(2)-2, which was characterized by CHN analysis, TG/DTA, FTIR, X-ray
      crystallography, and (solid-state and solution) 31P NMR spectroscopy. X-ray
      crystallography revealed that compound Me2NH(2)-2 was a monomeric species, but
      the Ge site per formula unit was not determined due to disorder of alpha-Dawson
      structure.

PMID- 19587999
TI  - Synthesis and structure of aluminium amine-phenolate complexes.
AB  - Reaction of Al(OiPr)3 with the tris-phenol amine ligand L1H3 in toluene at
      ambient temperature results in the formation of the iso-propanol adduct
      [HOiPr.Al(L1)]. Single crystal X-ray diffraction analysis reveals the structure
      to be a hydrogen bonded dimer. Reaction of Al(OiPr)3 (or AlMe3) with L1H3 in THF
      affords the related, and structurally characterised THF adduct, [THF.Al(L1)].
      Similar reaction of Al(OiPr)3 (or AlMe3) with the bis-phenol amine and tetra
      phenol diamine ligands, L2H3 and L3H4, results in the formation and isolation of
      the complexes [Al(L2)]2 and [Al(L3)H] respectively, both of which have been
      structurally characterised via single crystal X-ray diffraction studies. Reaction
      of the alkoxide bridged dimer [Al(L2)]2 with the strong Lewis base HMPA results
      in the formation of the monomeric HMPA adduct [HMPA.Al(L2)] which was also
      structurally characterised. The adduct [HOiPr.Al(L1)] and the dimer [Al(L2)]2
      were tested for their activity in the ring-opening polymerisation (ROP) of rac
      lactide under solvent-free conditions (130 degrees C). Under the conditions
      employed [Al(L2)]2 failed to produce polymer after 48 h, in stark contrast to
      [HOiPr.Al(L1)] which after 24 h and 48 h produced narrow molecular weight polymer
      (24 h: yield=25%, Mn=14500 and PDI=1.05; 48 h: yield=65%, Mn=47700 and PDI=1.06).

PMID- 19588000
TI  - Loading silica with metals (palladium or platinum) under mild conditions by using
      well-defined molecular precursors.
AB  - The loading of pre-treated amorphous silica with platinum or palladium was
      carried out by using the molecular precursors Pt2(micro-Cl)2Cl2(CO)2, or
      Pd2(micro-Cl)2Cl2(CO)2, respectively, which contain the required amount of
      coordinated CO to carry out the formation of the metal particles upon contact
      with moisture. The reactivity of the well-soluble mononuclear platinum complex
      cis-PtCl2(CO)2 with stoichiometric amounts of water was investigated either under
      N2 or CO. The metal nanoparticles produced on the silica matrix have been
      characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD)
      and transmission electron microscopy (TEM). The catalytic performance of the
      silica-supported metals thus produced was evaluated in the hydrogenation of
      cyclohexene.

PMID- 19588004
TI  - Nanophotonics: plasmonics and metal nanoparticles.

PMID- 19588005
TI  - Recombination rates for single colloidal quantum dots near a smooth metal film.
AB  - This paper presents experimental distributions of recombination rates for
      excitons in individual CdSe-ZnS core-shell quantum dots separated from a smooth
      gold film by a nanometre-scale dielectric layer. By measuring emission kinetics
      as a function of time, we obtain intrinsic recombination rates for single quantum
      dots. The distribution of recombination rates broadens and its maximum value
      increases as the separation between the dots and the metal decreases. The results
      agree with a semiclassical model that takes into account the randomly oriented
      two-dimensional dipole moments of the quantum dots.

PMID- 19588006
TI  - Gain and loss of propagating electromagnetic wave along a hollow silver nanorod.
AB  - Using the discrete dipole approximation (DDA) method, we examined the
      electromagnetic wave propagation along a hollow silver nanorod with subwavelength
      dimensions. The calculations show that light may propagate along the hollow
      nanorod with growing intensities. The influences of the shape, dimension, and
      length of the rod on the resonance wavelength and the enhanced local electric
      field, |E|(2), along the rod were investigated. The resonance wavelength
      monotonically red-shifted with increasing rod dimension perpendicular to the
      polarization direction. The resonance peak initially shifted to blue with
      increasing rod dimension parallel to the polarization direction and eventually
      shifted to red after a threshold value. For the hollow rods with similar cross
      sections, the square and rectangular rods produced greater enhanced electric
      fields along the rods. For the rectangular hollow rods with a fixed 10 nm thick
      shell and 100 nm long edge perpendicular to the polarization direction, light
      propagates along the outer surface of the rods when the parallel edge length is
      larger than 50 nm. The propagating wave with higher intensities is confined
      inside the hollow rods when the parallel edge length is less than 50 nm.

PMID- 19588007
TI  - Two-photon imaging of localized optical fields in the vicinity of silver
      nanowires using a scanning near-field optical microscope.
AB  - We report a near-field two-photon excitation imaging technique for silver
      nanostructures to visualize optical fields in the vicinity of nanostructures. We
      have found that the excitation image of an isolated wire shows an oscillating
      feature along the long axis of the wire. The period of the oscillation is in good
      agreement with that of plasmon wavefunctions resonant with the excitation light.
      The oscillation was thus attributed to the resonant plasmon wavefunction. We also
      found that bundles of wires exhibit more intense photoluminescence signals than
      do isolated wires, particularly at junctions between wire ends and the shafts of
      other wires, which was attributed to the amplified optical fields at the ends of
      nanowires or interstitial gaps between the wires. We discuss the mechanism of the
      photoluminescence from silver nanowires. The photoluminescence is most probably
      attributed to emission from the oxidized surface layer of the silver nanowires,
      which is enhanced in resonance with plasmons on the wires.

PMID- 19588008
TI  - Anisotropy effects on the time-resolved spectroscopy of the acoustic vibrations
      of nanoobjects.
AB  - The impact of spherical symmetry breaking and crystallinity on the response of
      the vibrational acoustic modes of a nanoobject in frequency- and time-domain
      experiments is investigated using the finite-element analysis method. The results
      show that introduction of shape anisotropy, i.e., evolution from a nanosphere to
      a nanorod, modifies the periods of the fundamental radial and quadrupolar modes
      and leads to activation of a quadrupolar-like mode in time-domain studies. In
      contrast, crystallinity is shown to have a negligible impact on the breathing
      mode frequency of a nanosphere formed by a cubic crystal and does not activate
      any quadrupolar mode. The effect of an anisotropic excitation in time-resolved
      measurements of a large nanosphere is also discussed.

PMID- 19588009
TI  - Coupling to light, and transport and dissipation of energy in silver nanowires.
AB  - Transient absorption experiments with diffraction-limited spatial resolution have
      been used to study the optical absorption properties and dynamics of isolated,
      single silver nanowires. The images and polarization analysis show that the near
      IR pump and near-UV probe beams couple to fundamentally different electron
      motions. The near-IR pump laser excites the propagating surface plasmon polariton
      (SPP) modes of the wires when focused at the ends, and multipolar plasmon modes
      (antenna modes) for medial excitation. The images show that these two modes have
      comparable optical absorption cross-sections. In contrast, the near-UV probe
      couples to the transverse plasmon resonance of the wire independent of the
      spatial position. For either end-on or medial excitation, pump laser absorption
      causes lattice heating and coherently excites the breathing vibrational mode of
      the nanowires. The vibrational quality factors depend on the acoustic impedance
      mismatch between the nanowire and the environment, and are similar to those
      recently measured for silver nanocubes. Experiments performed with spatially
      separated pump and probe beams, with the pump beam focused at one end to excite
      the propagating SPP modes, show that the amplitudes of the initial transient
      absorption signal and the breathing motion decrease with distance along the wire.
      This arises because the propagating SPP mode decays as it moves down the wire,
      which reduces the number of electronic excitations and, therefore, the signal
      level in the experiments. The measured length scale for the SPP decay is similar
      to that obtained in previous light scattering experiments.

PMID- 19588010
TI  - The versatile colour gamut of coatings of plasmonic metal nanoparticles.
AB  - We have investigated the colour gamut of coatings produced by the growth of
      plasmonically-active coatings of cap-shaped Au or Ag nanoparticles on a
      transparent substrate. The control of colour and spectral selectivity that can be
      obtained by the manipulation of the rates of nucleation and growth were explored
      using a combination of experiment and calculation. In our experimental work the
      Au nanoparticles were grown in situ using a wet chemical electroless plating
      technique while the Ag nanoparticles were produced by physical vapour deposition.
      The optical properties were numerically simulated using the discrete dipole
      approximation. The resulting measured or calculated transmission spectra were
      mapped to the CIE L-a -b colour space. The aspect ratio of the nanoparticles was
      the primary factor in determining the colours in both cases. However, increasing
      the nucleation rate of the particles resulted in them becoming more closely
      packed, which also red-shifted the optical extinction peak of the structure due
      to interactions of their near-fields. This caused an enhancement in the blue
      component of the transmitted light. Coatings of Ag particles had a significantly
      wider and brighter colour gamut than those of Au.

PMID- 19588011
TI  - Probing the surface-enhanced Raman scattering properties of Au-Ag nanocages at
      two different excitation wavelengths.
AB  - The surface-enhanced Raman scattering (SERS) properties of bimetallic Au-Ag
      nanocages has been thoroughly investigated by changing the nanocage composition,
      localized surface plasmon resonance (LSPR) peak position and excitation
      wavelength. We found a significant dependency on excitation wavelength for the Au
      Ag nanocages, independent of the underlying LSPR, which can be extended to other
      bimetallic SERS substrates. While it is well-understood that plasmon damping can
      occur for Au nanoparticles when their LSPR peaks are close to interband
      transition frequencies and thereby attenuate SERS intensities, this study probes
      an additional aspect and shows that SERS intensities are reduced when the
      excitation light source is near interband transition frequencies regardless of
      the LSPR location.

PMID- 19588013
TI  - White light scattering spectroscopy and electron microscopy of laser induced
      melting in single gold nanorods.
AB  - We present the first measurements of laser induced melting and reshaping of
      single gold nanorods. Using a combination of white light scattering spectroscopy
      and electron microscopy we find a melting energy of 260 fJ for nanorods with an
      average size of 92 x 30 nm. Contrary to previous reports on ensembles of
      nanorods, this melting energy corresponds well to the theoretical prediction of
      225 fJ. We observe a gradual shape change from a long and thin rod to a shorter
      and wider rod, which eventually collapses into a sphere when enough laser energy
      is deposited. We also observe that higher aspect ratio particles are
      thermodynamically less stable, leading to a greater reduction of the aspect ratio
      at lower laser pulse energy densities.

PMID- 19588014
TI  - Influence of the close sphere interaction on the surface plasmon resonance
      absorption peak.
AB  - Effects of agglomeration in optical properties of noble metal colloids (gold)
      have been calculated by an integral equation formalism valid for small (around 6
      nm) nanoparticles in the spectral region corresponding to surface plasmon
      resonance (SPR). These calculations are characterized by their accuracy and for
      the generality of their solutions, which do not depend on the nature of the
      materials nor the wavelength of the incident electric field. Chains of two
      (dimers), three (linear trimers) and four (linear tetramers) spheres have been
      taken as geometric models. Results indicate that for distances between spheres
      larger than 0.3 times the diameter, only dipolar interactions are relevant. For
      smaller distances between spheres, multipolar interactions generate low frequency
      modes that transform into a continuous band in the limiting case of touching
      spheres, band asymmetry and SPR broadening. Additionally, strong and sharp
      oscillation corresponding to surface charge density and electric field appear in
      the close neighborhood of sphere contact. These features are very difficult to
      determine by ad-hoc simulations but they should be taken into account when
      dealing with nearly touching nanosphere systems.

PMID- 19588012
TI  - The effect of surface roughness on the plasmonic response of individual sub
      micron gold spheres.
AB  - Nanoscale surface corrugation strongly determines the plasmonic response of gold
      nanoparticles with dimensions of several tens of nanometres. Scattering spectra
      of individual spheres with a rough surface were found to red-shift and broaden.
      The plasmon modes exhibited quadrupole damping, in contrast to particles with
      smooth surfaces. Additionally, rougher spheres display a higher SERS activity,
      which demonstrates the crucial role of nanoscale surface texturing on the
      plasmonic response of gold particles.

PMID- 19588015
TI  - Frequency-dependent fluidity and conductivity of an ionic liquid.
AB  - The frequency- and temperature-dependent shear fluidity, f(nu,T), of the ionic
      liquid [BMIm]BF(4) is presented and compared with its ionic conductivity,
      sigma(nu,T). [BMIm]BF(4) is short for 1-butyl-3-methyl-imidazolium
      tetrafluoroborate. Its DC fluidity, f(DC)(T), and DC conductivity, sigma(DC)(T),
      are non-Arrhenius and superimpose in an Arrhenius-type representation if the
      respective inverse temperature axes are made to differ by a small amount, Delta =
      (1/T(multiply sign in circle)- 1/T) > 0. The observed superposition suggests that
      f(nu,T) should display a frequency dependence similar to sigma(nu,T(multiply sign
      in circle)). We have therefore measured f(nu,T) of [BMIm]BF(4) over five decades
      of frequency at different temperatures. The spectra thus obtained corroborate our
      expectations. We model our experimental results in terms of the MIGRATION concept
      and arrive at the conclusion that f(nu,T) and sigma(nu,T(multiply sign in
      circle)) are Fourier transforms of quite similar time correlation functions.

PMID- 19588016
TI  - HOx radical regeneration in the oxidation of isoprene.
AB  - We propose, and quantify from first principles, two novel HO(x)-regenerating
      unimolecular reactions in isoprene oxidation, which are estimated to yield in
      pristine tropical forest conditions about 0.7 HO(2) and 0.03 OH radicals per
      isoprene oxidized; it is further argued that the photolabile coproduct of HO(2)
      can be a major source of OH, with a yield of the order of 1. The newly proposed
      chemistry could provide a rationalization for the unexpectedly high OH
      concentrations often observed in forested environments, such as over the Amazon
      forest in the recent Gabriel campaign.

PMID- 19588017
TI  - Activation of X-H and X-D bonds (X = O, N, C) by alkaline-earth metal monoxide
      cations: experiment and theory.
AB  - Experimental investigations are reported for reactions of MO (+) (M = Ca, Sr, and
      Ba) with elemental hydrides water, ammonia and methane proceeding in the gas
      phase at 295 +/- 3 K in helium buffer gas at a pressure of 0.35 +/- 0.01 Torr.
      Measurements were taken with an inductively-coupled plasma/selected-ion flow tube
      (ICP/SIFT) tandem mass spectrometer and a novel electrospray ion source/ion
      selection quadrupole/selected-ion flow tube/triple quadrupole (ESI/qQ/SIFT/QqQ)
      mass spectrometer. All three alkaline-earth metal oxide ions exclusively abstract
      a H-atom from the three hydrides with rate coefficients > 1 x 10(-11) cm(3)
      molecule(-1) s(-1). Formation of metal hydroxide ion was followed by sequential
      addition of water or ammonia, but not methane. Density functional calculations
      have provided potential energy surfaces for the X-H bond activations leading to H
      atom abstraction as well as those for O-atom transfer and H(2)O elimination (with
      ammonia and methane). A comparison of experimental and theoretical isotope
      effects points toward a mechanism involving the direct atom transfer from XH and
      XD to O in MO (+)via a three-centered transition structure.

PMID- 19588018
TI  - Parallel ultrafast E-C ring closure and E-Z isomerisation in a photochromic
      furylfulgide studied by femtosecond time-resolved spectroscopy.
AB  - The photo-induced parallel E-->C ring closure and E-->Z isomerisation reactions
      of the (E) isomer of the photochromic furylfulgide 2-[1-(2,5-dimethyl-3-furyl)
      ethylidene]-3-isopropylidene succinic anhydride () in n-hexane have been studied
      using femtosecond time-resolved spectroscopy. Broadband transient absorption data
      after femtosecond laser excitation at lambda(pump) = 335 nm provide time
      constants of 100 fs and 250 fs that belong to the formation of the (C) and the
      (Z) isomers, respectively, to yield a (C):(Z) product ratio of about 2:1. The
      results are consistent with a conformer-specific photoreaction of the (E)-isomer
      of , where one conformer (alpha) undergoes predominantly E-->C ring closure and
      the other (beta) E-->Z isomerisation, or alternatively with an ultrafast
      branching of the excited wavepacket of the alpha-conformer within Deltat < 250 fs
      after the pump pulse. The observed isomerisation times suggest that the ensuing
      transformations proceed via distinctive conical intersections between the
      respective potential energy hypersurfaces. Oscillations of the transient
      absorption with frequencies of approximately 64 and 114 cm(-1) are found and
      interpreted as excited-state vibrations induced during the E-->Z isomerisation
      reaction. Slower spectral dynamics at delay times up to approximately 10 ps
      reflect the cooling of the vibrationally hot reactant and product molecules after
      their return to their electronic ground states. Time-dependent DFT calculations
      were performed to shed light on the reaction coordinates involved. The emerging
      picture for the dynamics of obtained in this work is of interest in the broader
      context for our understanding of conformer-specific photochemistry and competing
      ultrafast reactions in polyatomic molecules.

PMID- 19588019
TI  - Charge separation and photocurrent polarity-switching at CdS quantum dots
      assembly in polyelectrolyte interfaced with hole scavengers.
AB  - Significant charge separation and potential-dependent photocurrent polarity
      switching are reported at multilayers of polyacrylate-capped CdS quantum dots (Q
      CdS, d = 3.6 +/-0.5 nm) assembled in poly(diallydimethylammonium chloride) with
      an alkaline sulfide solution interface. The films were deposited by dip self
      assembly or dip-spin self-assembly, and photocurrents were enhanced up to 2-fold
      by the latter method and reached a maximum at 4-6 bilayers. The monochromatic
      incident-photon-to-current-conversion efficiency equalled 6.5% at 340 nm and 2.1%
      at 440 nm at a 6-bilayer film in the sulfide electrolyte. The photocurrent
      magnitude and direction were found to depend on the assembly method, number of
      bilayers, film history, electrode potential and solution redox species. While
      significant anodic and cathodic photocurrents were measured in sulfide, the film
      acted predominantly as a photocathode in the presence of another hole scavenger,
      ascorbic acid. Charge separation leading to a cathodic photocurrent in the
      presence of hole scavengers is possibly mediated by a photo-oxidized species in
      the multilayers, which facilitates net photogenerated hole transfer to the
      electrode at reducing potentials.

PMID- 19588020
TI  - Faradaic currents during electroforming of resistively switching Ag-Ge-Se type
      electrochemical metallization memory cells.
AB  - Resistive switching due to electrochemical filament formation and dissolution is
      observed in a variety of materials. Mostly, an electroforming process is required
      to modify the active material and form a first filament. In this study, the
      forming process and low current resistive switching in Ag/Ag-Ge-Se/Pt memory
      cells was investigated. In contrast to most other resistively switching memory
      devices, the first current-voltage cycle was needed to reduce the metal content
      in the chalcogenide layer. Temperature dependent and sweep-rate dependent
      measurements of the faradaic current were performed, and the metal content in the
      Ag-Ge-Se thin film was estimated. After forming, resistive switching with a write
      current of only 1 nA was observed demonstrating the feasibility of the
      fabrication of memory cells with ultra low power consumption.

PMID- 19588021
TI  - Ab initio study of the structure and magnetism of atomic oxygen adsorbed Scn (n =
      2-14) clusters.
AB  - We have investigated the structure and magnetism of atomic oxygen adsorbed Sc(n)
      (n = 2-14) clusters by using the ab initio density functional theory approach.
      The oxygen atom tends to attack the hollow site in the ground state structures,
      and the bridge site in some metastable structures. The adsorption energies
      exhibit clear size-dependent variation, with maxima at n = 6, 10, 12 and minima
      at n = 4, 7 and 13, which can be assigned to the stability of the corresponding
      pure Sc(n) clusters. The incoming O atom exhibits great influence on the
      magnetism of the clusters. The magnetic moments of the Sc(n) clusters are partly
      or totally quenched at n = 2, 4, 6, 10, 12, 13, and 14, and enhanced at n = 7, 9,
      and 11 upon the addition of O, particularly the magnetic moment increases from 1
      to 5 micro(B) for n = 11 and decreases from 19 to 7 micro(B) for n = 13. The
      different magnetic responses to O adsorption are further investigated using the
      Hirshfeld population analysis and partial and local density of states analysis.

PMID- 19588022
TI  - Two-dimensional electronic spectra of an aggregating dye: simultaneous
      measurement of monomeric and dimeric line-shapes.
AB  - We present a sequence of two-dimensional electronic spectra of a prototypical
      cyanine dye, whose spectral properties in aqueous solution are determined by the
      formation of a monomer-dimer equilibrium. Quantum-chemical methods are utilized
      to calculate the structure and absorption properties of the two species involved.
      Our spectroscopic results simultaneously characterize the spectral line-shapes of
      the two species in terms of underlying dynamic and static disorder, and
      demonstrate how the two-dimensional technique allows the exploitation of high
      spectral and temporal resolution in one and the same experiment. The distinctly
      different spectral relaxation dynamics are quantified in a two-dimensional line
      shape analysis, by extracting the time dependent ratios of the diagonal and anti
      diagonal peak-widths. Our findings are in line with theoretical considerations,
      that predict the fluctuational dynamics of an excitonic dimer state to be
      exchange-narrowed by excitation delocalization.

PMID- 19588023
TI  - An integrated experimental and theoretical investigation on Cu(hfa)2. TMEDA:
      structure, bonding and reactivity.
AB  - The physico-chemical properties of the beta-diketonate diamine Cu(ii) compound
      with hfa (1,1,1,5,5,5-hexafluoro-2-4-pentanedionate) and TMEDA (N,N,N',N'
      tetramethylethylenediamine), Cu(hfa)(2).TMEDA, have been thoroughly investigated
      via an integrated multi-technique experimental-computational approach. In the
      newly found orthorhombic polymorph, as revealed by low temperature single-crystal
      X-ray studies, the complex is present as a monomer with a distorted octahedral
      geometry at the Cu(ii) centre. The compound sublimates, without premature side
      decompositions, at 343 K and 10(-3) Torr. The structural, vibrational, electronic
      and thermal behavior of the neutral Cu(hfa)(2).TMEDA complex has been
      investigated along with its fragmentation pathways, initiated by the release of
      an anionic hfa ligand with formation of a positive Cu(hfa).TMEDA(+) ion. Joint
      experimental and theoretical analyses led to the rationalization of the first
      fragmentation steps in terms of the Cu(ii)-ligands bonding properties and Jahn
      Teller distortion. The present study suggests applications of Cu(hfa)(2).TMEDA as
      a precursor for copper and copper oxide materials by Chemical Vapor Deposition.

PMID- 19588027
TI  - A framework for current public mental health care practice in South Africa.
AB  - One of the main aims of the new Mental Health Care Act, Act No. 17 of 2002 (MHCA)
      is to promote the human rights of people with mental disabilities in South
      Africa. However, the upholding of these rights seems to be subject to the
      availability of resources. Chapter 2 of the MHCA clarifies the responsibility of
      the State to provide infrastructure and systems. Chapters 5, 6 and 7 of the Act
      define and regulate the different categories of mental health care users, clarify
      the procedures around these categories and spell out mental health practitioners'
      roles and responsibilities in this regard. Also according to the National Health
      Act No. 61 of 2003, the State remains the key role player in mental health care
      provision, being responsible for adequate mental health infrastructure and
      resource allocation. Due to "limited resources" practitioners however often work
      in environments where staff ratios may be fractional of what should be expected
      and in units of which the physical structure and security is totally inadequate.
      The interface between professional responsibility of clinical workers versus the
      inadequacy of clinical interventions resulting from infrastructure and staffing
      constraints needs to be defined. This paper considered recent legislation
      currently relevant to mental health care practice in order to delineate the
      legal, ethical and labour framework in which public sector mental health
      practitioners operate as state employees. These included the Mental Health Care
      Act, No.17 of 2002; the National Health Act, No. 61 of 2003 and the proposed
      Traditional Health Practitioners Act, No. 35 of 2004. Formal legal review of and
      advice on this legislation as it pertains to public sector mental health
      practitioners as state employees, is necessary and should form the basis of the
      principles and standards for care endorsed by organized mental health care
      practitioner groups such as the South African Society of Psychiatrists (SASOP).

PMID- 19588026
TI  - Partnerships in publishing and developing world publications.

PMID- 19588024
TI  - A direct ab initio molecular dynamics (MD) study on the benzophenone-water 1 : 1
      complex.
AB  - Direct ab initio molecular dynamics (MD) method has been applied to a
      benzophenone-water 1 : 1 complex Bp(H(2)O) and free benzophenone (Bp) to
      elucidate the effects of zero-point energy (ZPE) vibration and temperature on the
      absorption spectra of Bp(H(2)O). The n-pi transition of free-Bp (S(1) state) was
      blue-shifted by the interaction with a water molecule, whereas three pi-pi
      transitions (S(2), S(3) and S(4)) were red-shifted. The effects of the ZPE
      vibration and temperature of Bp(H(2)O) increased the intensity of the n-pi
      transition of Bp(H(2)O) and caused broadening of the pi-pi transitions. In case
      of the temperature effect, the intensity of n-pi transition increases with
      increasing temperature. The electronic states of Bp(H(2)O) were discussed on the
      basis of the theoretical results.

PMID- 19588028
TI  - Parenting stress of caregivers of young children who are HIV Positive.
AB  - OBJECTIVE: Paediatric HIV remains a major challenge in Sub-Saharan Africa.
      Paediatric HIV is a multi-generational disorder with far-reaching implications
      for the whole family. Parenting stress in caregivers of HIV infected children has
      been studied in developed countries but never in South Africa. The aim of this
      study was to determine the extent of parenting stress in caregivers of children
      infected with HIV in South Africa. Further objectives were to monitor the levels
      of stress over one year after caregivers started attending a paediatric HIV
      clinic and to ascertain what factors were predictive of a decrease in parenting
      stress over that time. METHOD: One hundred and twenty two caregiver and children
      dyads were recruited into this study. Caregivers completed the Parenting Stress
      Index/ Short form at baseline and after six and 12 months. Demographic
      information was collected and the children's heights, weights and CD4 counts were
      recorded at each visit. RESULTS: The families that participated in this study
      came from very poor socio-economic backgrounds. Eighty five percent of the
      children were still being cared for by their biological mothers. The parenting
      stress levels of the caregivers in this study were extremely high at baseline.
      Although the parenting stress levels did come down significantly over the study
      period (p< 0.001) they remained high and warrant further investigation and
      management. A better level of education, better housing facilities and fewer
      adults living in the household were the three most important factors predicting a
      decrease in parenting stress over a one year period. CONCLUSION: Parenting stress
      of caregivers of young children infected with HIV is extremely high and warrants
      further investigation and long term management.

PMID- 19588030
TI  - Prevalence and clinical characteristics of obsessive-compulsive disorder and
      obsessive compulsive symptoms in Afrikaner schizophrenia and schizoaffective
      disorder patients.
AB  - OBJECTIVE: There is evidence of variation in the prevalence of co-morbid
      obsessive-compulsive disorder in schizophrenia amongst ethnic groups. This study
      evaluated the lifetime prevalence and clinical characteristics of obsessive
      compulsive disorder (OCD)/ obsessive-compulsive symptoms (OCS) in Afrikaner
      schizophrenic and schizoaffective disorder patients. METHOD: An ongoing genetic
      study of schizophrenia is currently being conducted on the Afrikaner founder
      population. In this cohort of 400 subjects from the original genetic study, we
      identified 53 subjects with schizophrenia or schizoaffective disorder and co
      morbid OCD/OCS (study group). They were matched for gender and age of onset of
      illness with 59 subjects who do not have OCD/OCS (control group). The diagnostic
      instrument used in this cohort is the Diagnostic Interview for Genetic Studies
      (DIGS) version 2, which has been translated into Afrikaans. In addition to the
      DIGS, information for the relevant clinical characteristics reported in this
      study was also drawn from a detailed narrative chronological summary report and
      clinical files. A checklist was completed. RESULTS: The prevalence of co-morbid
      OCD/OCS amongst 400 subjects with schizophrenia or schizoaffective disorder was
      13.2% [n=53] of which 40 were male and 13 female patients. The prevalence of OCD
      was 10.7% and OCS was 2.5%. Contamination obsessions [n=17] were the most common
      type of obsession reported, followed by religious obsessions [n=8]. The most
      prevalent compulsions were repetitive rituals [n=32] followed by checking
      behaviour [n=22]. Onset of psychotic symptoms was found to be insidious in 86.8%
      of the study group compared to 24.6% of the control group (p<0.0001). Second
      generation antipsychotic use was found to be statistically more prevalent in the
      study group (77.4%), compared to the control group (45.8%) (p=0.0008). 73% of the
      study group experienced depressive symptoms compared to 50.8% of the control
      group. Both groups were found to have a similar incidence of suicidal thoughts
      and suicide attempts. Substance abuse amongst the control group was significantly
      higher (35.9%) compared to the study group (19.2%) (p <0.05). Cannabis was most
      commonly abused in both groups, followed by alcohol. CONCLUSION: The prevalence
      rate of 13.2% of co-morbid OCD/OCS in Afrikaner schizophrenia and schizoaffective
      disorder patients differs from findings in other ethnic groups, suggesting the
      possible role of genetic and cultural factors in the prevalence of co-morbid
      OCD/OCS. Second-generation antipsychotic use amongst schizophrenia and
      schizoaffective disorder patients with co-morbid OCD/OCS was found to be
      significantly higher than in those without co-morbid OCD/OCS. Clinical
      characteristics of Afrikaner schizophrenics and schizoaffective disorder patients
      with and without co-morbid OCD/OCS are the same, both groups were associated with
      significant psychopathology and a poor prognosis.

PMID- 19588029
TI  - Polypharmacy in psychiatric out-patient practice in northern Nigeria.
AB  - OBJECTIVE: To describe and analyze patterns of polypharmacy among psychiatric
      outpatients in northern Nigeria and identify predictors of psychotropic
      polypharmacy. METHOD: A cross-sectional study, using chart review of new patients
      at out-patient clinics of two regional psychiatric hospitals in northern
      Nigeria,measuring rates, patterns and predictors of psychotropic polypharmacy.
      RESULTS: A total of 278 patients were seen, of whom 92%were given two or more
      psychotropic agents.The pattern of psychotropic polypharmacy revealed that total,
      multi-class and adjunctive polypharmacy rates were high, while augmentation and
      same class polypharmacy rates were low. Age of respondent and diagnosis were the
      factors associated with total polypharmacy. CONCLUSION: The complex interplay of
      factors influencing physician prescription practices requires that a more
      pragmatic approach be adopted in efforts to curtail polypharmacy practice, rather
      than a wholesale, absolute condemnation of the practice.

PMID- 19588032
TI  - Publishing, publications and African psychiatry.

PMID- 19588031
TI  - Psychiatric disorders among war-abducted and non-abducted adolescents in Gulu
      district, Uganda: a comparative study.
AB  - OBJECTIVE: We aimed to assess the nature and patterns of psychiatric disorders
      among adolescents who had been war-abducted in the war in northern Uganda,
      compared to non-abducted adolescents living in Gulu district, Uganda. METHOD: A
      cros sectional study that used an unmatched case-control design compared 82
      abducted and 71 non-abducted adolescents for scores on measures of psychological
      distress and for selected psychiatric diagnoses using the Strength and
      Difficulties Questionnaire (SDQ) and the Mini International Neural-Psychiatric
      Interview for Children and Adolescents English version 2.0 (M.I.N.I-KID).
      RESULTS: More than 90% of adolescents reported exposure to severe trauma, either
      through direct or indirect experiences. Significantly more war abducted
      adolescents reported PTSD (26.8%v.12.7%) (p=0.03) major depression (19.5%v.4.2%)
      (p=0.004), and generalised anxiety disorder (13.4v.4.2%) (p=0.049) than non
      abducted adolescents. By contrast, non-abducted adolescents reported more past
      suicidality (p=0.004, chi(2)=8.2) than adolescents who were abducted. However,
      despite high rates of psychiatric disorder, these adolescents had good
      psychosocial adjustment. CONCLUSION: Adolescents in war affected areas whether
      warabducted or not have varied and clinically significant emotional responses to
      different kinds of traumatic exposure. In a war-affected area, the development of
      a sustainable service for adolescents that tries to address the full range of
      mental health problems may be more appropriate than a psychological trauma
      service that focuses on one diagnosis.

PMID- 19588033
TI  - The central noradrenergic system: an overview.
AB  - The central noradrenergic system belongs to a group of brainstem neuromodulatory
      systems previously referred to as the ascending reticular activating system. In
      this article a heuristic model is presented of the central noradrenergic system
      depicting the major projections to other cerebral areas, its interactions with
      other neuromodulatory systems, mechanisms through which it can influence cerebral
      function, as well as the major functions and disorders associated with
      alterations in central noradrenergic activity. It is not the aim of this paper to
      provide fine detail on the various aspects, but rather to provide a concise
      overview where structure and function, as well as the interactions with other
      systems are brought together. The contents of the paper are summarized in a
      diagram.

PMID- 19588034
TI  - A survey of the prevalence of diabetes type 2 amongst schizophrenics in a chronic
      care treatment facility.
AB  - OBJECTIVE: The determination of the prevalence of type 2 diabetes in a group of
      patients suffering from schizophrenia who have been hospitalized in a chronic
      care facility and to consider the role of factors which may contribute to the
      increased risk of developing diabetes. METHOD: The hospital files of patients
      suffering from diabetes type 2 were reviewed and assessments were made in terms
      of age, gender and body mass index (BMI) duration of stay and co-existing medical
      conditions. Fasting blood glucose estimations were done on all schizophrenic
      patients not receiving treatment for diabetes. Medications of patients were
      recorded. A protocol was prepared and approval to conduct the study was obtained
      from the hospital authorities. RESULTS: Of 494 schizophrenic patients 19 (3.85%)
      were found to suffer from diabetes. 68% of patients in the diabetic group were
      found to be overweight in terms of BMI rating. Only one patient had a medical
      condition. Proportionately the number of women was relatively high. CONCLUSION:
      The prevalence if diabetes type 2 in a group of chronically ill hospitalised
      patients with schizophrenia is significantly lower than in outpatient
      populations. Residing in a facility long term may serve as a protective factor.
      The exclusion of psychological stressors such as isolation, poverty and
      abandonment may account for the finding.

PMID- 19588035
TI  - Needs and services at an in-patient psychotherapy unit.
AB  - OBJECTIVE: To describe the impact of services provided, during an admission,on
      unmet needs and correlates of unmet needs. METHOD: The study used a modified
      version of The Camberwell Assessment of Need (CAN) to assess the perceived needs
      of 100 patients on admission to a psychotherapy unit, Valkenberg Hospital, Cape
      Town. At discharge, the study documented the extent to which the patients had
      perceived services and interventions to be useful. RESULTS: The mean number of
      needs on admission was 8.6. At discharge, help received was highest for
      psychiatric needs. The services most often regarded as useful were organised
      group activities and therapies. Regression analysis suggests that a lower level
      of education and the presence of borderline personality traits contribute
      significantly to unmet need on discharge. CONCLUSION: The in-patient program is
      effective in meeting psychiatric needs, but less useful for addressing psycho
      social needs. These needs may exacerbate psychiatric problems and should be
      managed more actively before, during and after an in-patient stay.

PMID- 19588036
TI  - Clinical profile of acutely ill psychiatric patients admitted to a general
      hospital psychiatric unit.
AB  - OBJECTIVES: Helen Joseph Hospital in southern Gauteng Province is one of five
      specialist hospitals on the academic circuit of the University of
      theWitwatersrand. Against a background of new mental health legislation,
      implemented in South Africa during December 2004 with no formal mechanisms in
      place to monitor mental health services on different levels of care or in
      regions, a study with three objectives was undertaken, namely: (I) to provide a
      baseline on psychiatric morbidity and treatment outcome; (II) to establish the
      state of affairs analysis for mental health care and (III) to establish a
      framework for cost centre management. The current study focuses on objective one.
      METHOD: A retrospective clinical audit was undertaken of mental health service
      delivery, teaching and research at Helen Joseph Hospital over a one-year period
      from September 2003 to August 2004. This article reports on the two service
      delivery datasets identified: the "Inpatient Discharge Summary Report" and the
      "Consultation/Liaison Report". RESULTS: A total number of 438 service users were
      admitted and a monthly average of 80 consultation/liaison assessments was
      conducted during the study period. Persistent unfavourable nursing staff ratios
      continued, while the number of service users from other African countries was
      generally underrated. Non-compliance and substance abuse contributed
      significantly to the admission of service users. Schizophrenia was indicated as
      the most likely diagnosis in almost a quarter of cases. CONCLUSION: Morbidity and
      treatment outcome at Helen Joseph Hospital will only be contextualized after the
      implementation of a regular clinical audit process in all the facilities of its
      referral network.

PMID- 19588037
TI  - Visual deterioration 1(1/2) years after wrapping an un-clippable anterior
      communicating artery aneurysm: report of a case and review of the literature
      regarding opto-chiasmatic arachnoiditis.
AB  - OBJECTIVE: Optochiasmatic arachnoiditis (OCA) is a serious complication that can
      occur after wrapping of aneurysms in the proximity of the optic pathways. This
      paper seeks to illustrate one such case with a view to drawing attention to the
      dangers of this practice. METHOD: Single case report and review of the
      literature. RESULTS: The clinical and radiological features of OCA are presented
      and discussed, which in this patient involved failing visual acuity as well as an
      inflammatory mass of the suprasellar area with oedema of the optic apparatus.
      CONCLUSION: Optochiasmatic arachnoiditis and its attendant visual morbidity is a
      serious condition. In the setting described, it arose as a result of wrapping an
      unclippable aneurysm. The tide of aneurysm management has turned, and presently
      more and more of them are being obliterated by endovascular techniques. Among
      other benefits, this reduces the likelihood of such complications as OCA.

PMID- 19588038
TI  - The African Journal of Psychiatry, one year on.

PMID- 19588039
TI  - Ensuring access to psychotropic medication in sub-Saharan Africa.
AB  - In this review article, the issues related to provision of psychotropic drugs in
      services in sub-Saharan Africa are explored. Problems encountered in procurement
      of drugs, their safe prescription and practical supply systems are discussed,
      with possible solutions suggested. The evidence-base for the preferential use of
      first-generation drugs is presented, with the practical implications for cost
      effective service delivery shown. Options for sourcing of quality drugs are
      outlined with practical examples. An argument is made for a wider range of
      medical personnel to be allowed to prescribe than is often currently the case.
      This is so as to allow for the scale up of community based psychiatric services
      which will otherwise fail to meet the needs of the majority of persons with
      mental illnesses, particularly in rural communities. Drug Revolving Funds are
      proposed as a means of managing supplies by local projects in a context of a lack
      of an alternative supply. Some suggestions are made for practical solutions to
      the problem of those cannot afford even cheaper medications.

PMID- 19588040
TI  - Obsessive-compulsive (oc) symptoms in psychiatric in-patients at Mathari
      hospital, Kenya.
AB  - OBJECTIVE: To document the prevalence of obsessive-compulsive disorders (OCD)
      among patients admitted at Mathari Psychiatric Hospital, Nairobi, Kenya. METHOD:
      This was a descriptive cross-sectional study conducted at the Mathari Hospital.
      RESULTS: Out of 691 patients interviewed, 84 (12.2%) had symptoms which met the
      Diagnostic and Statistical Manual of Mental Disorders (DSMIV) criteria for OCD,
      which started early in life. The clinicians had not recognized the OC
      symptoms/disorder. There were high co-morbidities between OCD and other
      Structured Clinical Interview for DSM-IV (SCID) core syndromes as well as
      psychotic symptoms often associated with schizophrenia. CONCLUSION: OC symptoms
      are common in psychiatric patients admitted at Mathari Hospital although such
      symptoms were clinically undetected and therefore not managed. The high co
      morbidities between OCD, other psychiatric disorders and other psychiatric
      symptoms pose clinical challenges in differentiating between psychotic symptoms
      perceived by the patients to have an external locus and OC symptoms perceived to
      have an internal locus. A more systematic clinical procedure for assessing all
      DSM-IV symptoms should be adapted as standard quality control practice in all
      patients, particularly those with psychotic symptoms.

PMID- 19588041
TI  - Predictors of psychiatric readmissions to the psychiatric unit of a tertiary
      health facility in a Nigerian city - a 5-year study.
AB  - OBJECTIVE: Little is known about predictors of readmission of psychiatric
      patients in the study environment. Knowledge of this, we believe could aid
      effective management of psychiatric patients, as well as judicious and equitable
      utilization of the limited mental health facilities in the North-central zone.
      The aim was to identify factors that may be predictive of readmissions to an in
      patient psychiatric facility of a Nigerian University Teaching Hospital. METHOD:
      A retrospective record review of all admissions and discharges to/from the
      psychiatric inpatient ward of University of Ilorin Teaching Hospital, (UITH)
      between May 2000 and April 2005. Patients and clinical characteristics were
      recorded and all the data were characterized according to age, gender, marital
      status, occupational status, length of stay on admission, number of admissions,
      and medication compliance. Data were analyzed with SPSS version 11 to derive the
      chi square figures, Pearson's correlation, and logistic regression. The level of
      statistical significance was set at 5%. RESULTS: Within the study period, 41.4%
      of cases were readmissions. Young age, longer length of stay, multiple admissions
      and the diagnosis of schizophrenia were predictive of readmission while
      medication non-compliance was not predictive. CONCLUSION: Provision of psycho
      education to both the patients and their families, identification of early
      symptoms of relapse, application of immediate and appropriate measures, and
      adequate record-keeping by health institutions are advocated.

PMID- 19588042
TI  - A longitudinal comparative analysis of economic and family caregiver burden due
      to bipolar disorder.
AB  - OBJECTIVE: to explain comparatively how economic and family caregiver burden in
      families with bipolar disorder patients change overtime. METHOD: one year follow
      up of economic and family caregiver burden was carried out on family caregivers
      of 190 bipolar, 55 diabetes, hypertension and asthma patients and 659 sick
      controls in the community. Population average generalized estimating equation was
      used to make longitudinal comparative analysis. RESULTS: bipolar patient family
      caregivers were found to be more burdened, for about 8 to 10 months of the year
      of study, than family caregivers of diabetes, hypertension and asthma and sick
      controls in the community. The average difference in family caregiver burden
      score between bipolar and diabetes, hypertension and asthma patient family
      caregivers was 4.36 (z = -8.75, P>|z|= 0.001); while the difference due to time
      between the two groups was 3.42 (z= -4.27, P>|z|= 0.001). Similarly, the average
      difference in family caregiver burden score between family caregivers of bipolar
      patient and sick controls in the community was 3.7 (z= -4.88, P>|z| 0.001). In
      terms of longitudinal caregiver burden difference, bipolar patients family
      caregivers were found to be more burdened than family caregivers of sick controls
      in the community with a burden score difference of 2.97 (z= -5.17, P>|z|= 0.001).
      CONCLUSION: more should be done to lessen the economic and family caregiver
      burden due to bipolar disorder.

PMID- 19588043
TI  - Burnout in staff working at the Mathari psychiatric hospital.
AB  - OBJECTIVE: As there are no data on burnout in staff in Kenyan psychiatric
      hospitals, this study sought to document the level of burnout among the staff at
      the Mathari Psychiatric Hospital. METHOD: This was a cross sectional descriptive
      study of staff working at Mathari Psychiatric Hospital. The hospital staff
      completed self-administered questionnaires on socio-demographic characteristics
      and work environment and the Maslach Burnout Inventory - Human Services and
      General Survey. Analysis of the data was undertaken using the Statistical Package
      for the Social Sciences (SPSS) version 11.5. RESULTS: Ninety-five percent of the
      respondents reported low to high emotional exhaustion while 87.8% reported
      depersonalization. Low accomplishment was reported by only 38.6% while 61.4%
      reported average to high personal accomplishment. Several work- and non-work
      related factors including young age, number of own children, number of years
      worked, heavy workload and low morale were positively associated with various
      syndromes of burnout. Relationships at work, with family and society were
      generally rated as average. The staff made recommendations on how to improve the
      social support system and work performance. CONCLUSION: High levels of burnout
      were reported. These should be addressed at individual, collective and
      institutional levels.

PMID- 19588044
TI  - Neurocognitive dysfunction in patients with obsessive compulsive disorder.
AB  - OBJECTIVE: Although a dysfunctional prefrontal-striatal system is presupposed in
      obsessive-compulsive disorder (OCD), this is not unequivocally supported by
      neuropsychological studies. This study aims to study the neurocognitive
      dysfunctions in OCD patients, compared to controls; to study the variations in
      neurocognitive deficits with the duration of illness, as well as, the severity of
      the disease. METHOD: Thirty OCD patients were compared with thirty, age and
      education matched control subjects on computer based tests measuring executive
      functions, vigilance and spatial working memory. RESULTS: OCD patients performed
      poorly on all the neuro-cognitive parameters as compared to controls. The
      severity of illness had a positive correlation with poorer performance on CPT.
      There were no significant correlations between duration of illness and any
      parameters of cognition. CONCLUSION: The results suggest that OCD patients
      perform significantly worse on cognitive measures than controls. This is
      consistent with their poorer functional outcome. The results further indicate
      that on the basis of severity OCD patients are qualitatively distinguishable in
      neuropsychological terms, given their difference in the profiles of cognitive
      impairment.

PMID- 19588045
TI  - Samurais and psychiatry.

PMID- 19588046
TI  - Comment: samurai attack.

PMID- 19588047
TI  - The multidimensional assessment of psychopathology in mood and psychotic
      disorders. A proposal for Axis II in DSM-V/ICD-11.
AB  - The inclusion of dimensional elements in the psychiatric diagnostic systems have
      been advocated for many years, however it has been resisted due to concerns about
      clinical utility. Recent suggestions have been for a combination of categorical
      and dimensional data in future diagnostic classification systems. In this paper
      we discuss the overlap in symptom complexes between mood disorders and
      schizophrenia and a multi-dimensional model of the mood-psychosis interface. We
      propose that the personality diagnoses should be included in Axis I and suggest
      the inclusion of a five factor dimensional diagnosis of mood and psychotic
      disorders on Axis II of DSM-V/ICD-11.

PMID- 19588048
TI  - Establishing psychiatric registrars' competence in psychotherapy: a portfolio
      based model.
AB  - During most of the latter part of the last century, South Africa has followed
      international trends in the training of psychiatrists. Training programmes have
      become increasingly focused on the neurobiological aspects of psychiatric
      disorders with less attention being paid to psychotherapy. This is consistent
      with developments in psychiatric research. In the clinical arena this manifests
      as a focus on pharmacological and medically based interventions and a resulting
      relative inattention to non-pharmacological interventions, most especially
      psychotherapy. In an effort to address this imbalance there has been an
      international initiative, over the past two decades, to establish an acceptable
      level of competence in psychotherapy in the training of psychiatrists. A South
      African programme is needed that can take account of international trends and
      adapt them for the local context. In order to produce a programme for
      establishing competence in psychotherapy for psychiatric registrars at the Nelson
      R. Mandela School of Medicine, the authors examine directives for the development
      of psychotherapy skills from international regulatory bodies for graduate medical
      training and their application. Defining and setting preliminary standards for
      competence is emphasized. A programme based on five core psychotherapy components
      using a portfolio based model to facilitate learning and assessment of competence
      in psychotherapy, is proposed.

PMID- 19588049
TI  - Assertive community treatment in the South African context.
AB  - Although the integration of psychiatric services into the community has
      potentially been beneficial to many patients, this transition has not been
      without problems. A major obstacle to establishing successful community-based
      treatment in South Africa has been that the reduction in number of inpatients
      beds did not coincide with the development of adequate community resources. This,
      in combination with our patients' poor socio-economic circumstances, has
      contributed to a substantial increase in the so-called "revolving door" or high
      frequency use phenomenon in state psychiatric facilities. Clearly, there is need
      for a renewed approach to address this problem in our setting. With this in mind
      the APH in the Western Cape appointed three community treatment teams in January
      2007. This publication serves to give an overview of the Stikland Psychiatric
      Hospital team's experiences in the first 12 months since establishment. To date,
      we have been confronted by several challenges that complicate the successful
      implementation of an "assertive" outreach service in the South African context.
      However, there seems to be some hope as early findings demonstrate a reduction in
      number of admissions as well as inpatient days. Furthermore there has been a very
      positive response from service users, their families and other staff members
      leaving us to conclude that this initiative seems to be a much needed step in the
      right direction.

PMID- 19588050
TI  - Medical students' perceptions of accessibility and barriers to the utilisation of
      the University of Pretoria's support systems.
AB  - OBJECTIVE: A campus-based website was set up by medical students following their
      study that showed a low awareness and utilsation of support systems at the
      University of Pretoria. The aim of the website was to improve the utilisation of
      the existing support systems. This study evaluated the students' perception of
      the support systems and whether the website would resolve barriers hindering
      utilisation of support. METHOD: Focus groups were selected by theoretical
      sampling in the first and final quarter of the academic year. The sample group
      consisted of 120 medical students from all years of study. The transcribed tape
      recordings, field notes, e-mail responses and observations of the focus groups
      were analysed for themes by open, axial and selective coding. RESULTS: The
      medical students varied in their awareness of the available support systems. The
      majority were unaware of procedures to access the support systems and what
      services were offered by each. There were numerous barriers to utilising the
      support systems effectively. The barriers included the students' perception of
      failure in admitting that they require assistance and the remainder were mostly
      of an administrative nature. Most students were aware of the website but
      utilisation was minimal. CONCLUSIONS: The majority of students were aware of but
      underutilised the support systems for various reasons. The website failed to
      improve utilisation of the extensive existing support systems. The barriers
      suggest other ways of improving support that include addressing social support,
      socialisation and life skills training as well as streamlining the marketing of
      existing support systems.

PMID- 19588051
TI  - The utility of a rapid screening tool for depression and HIV dementia amongst
      patients with low CD4 counts- a preliminary report.
AB  - OBJECTIVE: To assess the utility of the International HIV Dementia Scale (IHDS)
      and Centre for Epidemiological Studies Depression Scale (CESD) as rapid screening
      tools of depression and HIV dementia amongst patients with low cluster of
      differentiation 4 (CD4) counts. METHOD: The rapid screening tools were tested on
      a sample of 20 patients with low CD4 counts who were recruited from the inpatient
      ward at McCord Hospital from August to October 2007. RESULTS: The CESD was found
      to have 91 % sensitivity and 44 % specificity. Using the recommended cut-off of
      10, the sensitivity of the IHDS was 88 %. The specificity was 50 %. The results
      suggest that CESD and IHDS are sensitive, however their low specificity may limit
      their clinical utility. CONCLUSIONS: This is a pilot study and no firm
      conclusions are drawn. Further research is needed to verify the high burden of
      depression and neuro-cognitive impairment (NCI) among people with low CD4. A
      larger study is needed to validate the IHDS in South Africa. Other researchers
      are encouraged to validate and determine the optimal cut off value for the IHDS
      in their local population.

PMID- 19588052
TI  - Antipsychotic prescription patterns in Xhosa patients with schizophrenia or
      schizoaffective disorder.
AB  - OBJECTIVE: To examine the degree to which South African physicians use similar
      treatment guidelines in their prescription of antipsychotic medication. METHOD:
      Data on the prescriptions for Xhosa patients with schizophrenia and
      schizoaffective disorder were retrospectively examined to investigate differences
      between three catchment areas in the Western Cape, especially in terms of
      clozapine use. RESULTS: There was an overall low rate (10.0%) of clozapine use
      and a relatively high occurrence of polypharmacy (28.6% of 510 patients). There
      were statistically significant differences between the three catchment areas in
      terms of clozapine (p=0.002) and haloperidol (p=0.001) use. Valkenberg hospital
      had the highest number of clozapine prescriptions and the lowest of haloperidol.
      Prescriptions of depot antipsychotics did not differ between catchment areas.
      CONCLUSION: Discrepancies in antipsychotic medicine prescription patterns were
      evident between the examined hospitals. It is becoming paramount for practical
      implementation of guidelines to be improved in South Africa to address, e.g., low
      clozapine use and the high frequency of polypharmacy.

PMID- 19588053
TI  - Service evaluation of a UK primary care-based allergy clinic: quality improvement
      report.
AB  - INTRODUCTION: Allergic diseases are common, increasing, and associated with
      significant morbidity and occasional, but potentially avoidable, mortality. There
      is widespread public, professional and government agreement about the poor
      quality of care received by many patients with allergic diseases in the UK. Many
      remain undiagnosed, few have access to specialist services, and the majority of
      primary care health professionals have no allergy training. We report an
      evaluation of a novel, UK NHS-funded primary care-based allergy service in North
      West London. METHODS: The clinic was run by a specialist allergy nurse and a
      general practitioner (GP) with a special interest in respiratory disease and
      allergy. Referrals from local GPs were made on dedicated proformas and handled
      according to developed and agreed community care pathways. RESULTS: 141/151 (93%)
      of those referred attended the clinic. On average, patients waited 15.7 (SD
      15.67) days from referral to an offer of an appointment and were seen 18.11
      (SD18.07) days from the date of referral. The majority of patients were referred
      for hives or wheals (61;40%), suspected food allergy (28;40%), multiple reasons,
      (19;12%) or rhinitis (19;12%). Skin prick and specific-IgE tests were performed
      on 69 (49%) and 19 (14%) patients respectively, with 4 (0.3%) patients having
      both. We estimated an overall saving of at least pound13,580 to the local health
      economy - through reduced secondary care referrals - during the nine months'
      duration of the clinic. Assessed using a validated patient satisfaction
      questionnaire, most patients rated their satisfaction with the service with an
      overall median score of 75% (IQR 65.64-82.32). CONCLUSIONS: A primary care
      allergy service provided by appropriately trained personnel can cater adequately
      for the majority of primary care referrals. This model provides a pathway of care
      that supports self-directed care, reduces inappropriate referrals, and encourages
      care in the local community. The model is one that could easily be developed
      further into a clinical assessment service for allergy including respiratory
      based (asthma) problems. This would expand the scope and ensure value for money
      as well as responding to a clinical need with significant incidence locally. The
      UK Department of Health should consider rolling out this primary care-based model
      nationally.

PMID- 19588054
TI  - Technology and its role in respiratory care.
AB  - INTRODUCTION: Telemonitoring, telemedicine, clinical and medical informatics or
      telecare, are terms used to describe the use of technology along with local
      clinical protocols to monitor remotely a patient's medical condition in their own
      home. In respiratory medicine, where large numbers of people have long term
      conditions such as asthma and chronic obstructive pulmonary disease (COPD), the
      role of such monitoring technology in the management of patients is of great
      interest. AIM: This review seeks to explore what evidence exists to support the
      deployment of technology to improve the care of people with respiratory
      conditions. METHOD: Narrative review. RESULT: A wide variety of technologies have
      been involved in asthma and COPD care, from management systems to self monitoring
      devices. Many studies report that staff and patients 'liked' the technology. The
      service, care and financial benefits to both patients and the health care system
      were less obvious. Many studies suffered from poor methodology and lacked clear
      endpoints. CONCLUSION: There is an enormous potential for telemonitoring to
      assist in the provision of better care for those with long term lung diseases.
      However, evidence of benefit is unclear and there remains a need for robust
      studies and answers to clear research questions for specific patient populations
      before such technologies can be recommended for widespread implementation.

PMID- 19588055
TI  - Food allergy and asthma.
AB  - Food allergy and asthma commonly co-exist in the same patient with approximately
      one-third of children with food allergy having asthma. When both atopic
      conditions are present a food allergic patient is placed at greater risk of
      having a fatal reaction from food allergen exposure. For this reason asthma
      should be diligently managed in a food allergic patient and these patients should
      be carefully instructed on allergen avoidance and the proper use of self
      injectable epinephrine. This review summarises the available literature regarding
      patients with both food allergy and asthma specifically looking at disease
      prevalence, IgE-mediated effects on the lower respiratory tract secondary to
      foods, the interplay of food additives and asthma, and food allergy as a risk
      factor for asthma morbidity with practical applications for clinicians.

PMID- 19588056
TI  - The impact of a telemetric chronic obstructive pulmonary disease monitoring
      service: randomised controlled trial with economic evaluation and nested
      qualitative study.

PMID- 19588057
TI  - Pre-vaccination distribution of human papillomavirus (HPV) genotypes in women
      with cervical intraepithelial neoplasia grade 3 (CIN 3) lesions in Slovenia.
AB  - BACKGROUND: High-risk human papillomaviruses (HPV) are the main etiological
      factor of cervical cancer. Cervical intraepithelial neoplasia grade 3 (CIN 3) is
      the latest pre-invasive stage of cervical cancer, with an approximately 20%
      progression rate to invasive cervical carcinoma. OBJECTIVE: To establish the pre
      vaccination distribution of HPV genotypes in Slovenian women with CIN 3 lesions,
      in order to assess the potential benefit of prophylactic HPV vaccination in
      Slovenia, and to provide baseline data for monitoring the potential replacement
      of HPV genotypes under selective pressure of HPV vaccines. METHODS AND RESULTS: A
      total of 261 cervical swabs collected from women with histologically confirmed
      CIN 3 lesions were analyzed using four genotyping methods: the Abbott RealTime
      High Risk HPV Assay, the Innogenetics INNO-LiPA HPV Genotyping Extra Test, and
      the in-house PGMY09/11, and CPI/CPIIg polymerase chain reaction (PCR) and
      sequencing. Of 261 samples, 253 (96.9%) were HPV positive. The most common HPV
      genotype in CIN 3 lesions in the Slovenian samples was HPV-16 (59.0%), followed
      by HPV-31 (7.5%), HPV-33 (7.1%), HPV-58 (5.0%), and HPV-51 (4.0%). The presence
      of more than one HPV genotype was detected in 49/253 (19.4%) samples. Together,
      HPV-16 and HPV- 18 accounted for 67.4% of CIN 3 lesions in this Slovenian
      population. CONCLUSION: The high proportion of CIN 3 lesions caused by HPV-16 and
      HPV-18 should further support the recent decision to include the prophylactic
      vaccination against HPV in the national vaccination program in Slovenia.

PMID- 19588058
TI  - Psychological correlates of quality of life in dermatology patients: the role of
      mental health and self-acceptance.
AB  - OBJECTIVES: Chronic skin diseases have been recognized as having a detrimental
      effect on patients' quality of life, also causing considerable mental discomfort.
      Reduced self-acceptance, low self-esteem, a negative body image, and a low sense
      of self-worth have been noted in patients with visible skin disorders. Yet in the
      available literature we could not find any data concerning the relationship
      between mental health status, self-image, and quality of life. This research,
      then, analyzes potential relationships between self-acceptance, mental health
      status, and quality of life in dermatology patients. MATERIALS AND METHODS: In
      total, 112 patients of the Occupational Diseases Outpatient Clinic and the
      Occupational and Environmental Allergy Centre of the Nofer Institute of
      Occupational Medicine (NIOM) were examined. The General Health Questionnaire
      (GHQ) was used to assess the patients' mental health; a Polish version of the
      Dermatology Life Quality Index (DLQI) was employed to assess life quality; and
      the Self-Acceptance Scale (SAS) served to obtain the patients' self-image.
      Results showed that there were statistically significant differences in self
      assessment of mental health and quality of life depending on ones's level of self
      acceptance. People with high self-acceptance are characterized by better mental
      health than those with low self-acceptance (t = 4.8; p = 0.00). Patients with a
      negative selfimage (compared to those with a positive self-image) also deem their
      quality of life to be poor (t = 3.1; p = 0.00). Results of regression analysis
      show that mental health status significantly affects the quality of life in
      dermatology patients; the standardized coefficient was beta = 0.42 (p < 0.0001).
      CONCLUSION: Relationships have been found to exist between the patient's mental
      health and both their subjective assessment of life quality and self-image.
      Taking into account the role of mental health as a potential determinant of
      quality of life among dermatology patients, and considering the strong
      correlation between self-acceptance and well-being, treatment should also focus
      on counseling.

PMID- 19588059
TI  - Erysipelas and lymphangitis in patients undergoing lymphedema treatment after
      breast-cancer therapy.
AB  - AIM: The aim of this study was to evaluate the prevalence of erysipelas and
      lymphangitis in a group of patients under treatment for lymphedema after breast
      cancer therapy. METHODS: A random observational prospective study of the
      incidences of lymphangitis and erysipelas was performed for 66 patients with arm
      lymphedema after breast-cancer treatment. The study was carried out between March
      2006 and December 2007 at the Godoy Clinic in Saoo Jose do Rio Preto, Brazil. The
      clinical evaluation of the participants was performed weekly before the start of
      treatment, with patients being required to immediately report any complications
      to the attending service. RESULTS: The mean time of follow-up of the patients
      between their treatment for breast cancer and the start of this study was 12.3
      months, and three complications (4.5%) occurred; two cases of lymphangitis were
      reported after insect bites and one case of erysipelas after a hand injury, with
      repeat episodes reported by all three patients. CONCLUSION: In spite of
      prophylactic advice regarding lymphangitis and erysipelas during treatment for
      lymphedema after breast-cancer therapy, patients are subject to complications;
      however, this in itself does not justify the use of prophylactic antibiotic
      therapy.

PMID- 19588060
TI  - A newborn with bullous pemphigoid associated with linear IgA bullous dermatosis.
AB  - A 16-day-old boy was admitted to our clinic with localized blisters on the neck,
      cheeks, earlobes, and oral cavity and with erythema on the toes, in addition to
      poor weight gain and respiratory distress. A physical examination revealed
      several erythematous plaques with tense bullae, multiple vesicles, and erosions
      on the left toes, neck, earlobes, and face as well as erosive lesions on the
      anterior part of the oral cavity, lips, and buccal mucosae. A bronchoscopic
      examination revealed bullous lesions in the upper respiratory tract and on the
      epiglottis. A skin biopsy suggested a diagnosis of bullous pemphigoid (BP).
      Because of the severe mucosal involvement, further investigations including
      various immunological techniques were performed. The case was diagnosed as BP
      associated with linear IgA bullous disease (LAD). Complete remission without any
      scarring was achieved after three weeks of oral methyl prednisolone treatment. A
      correct differential diagnosis of bullous diseases is important for determining
      the prognosis and expected response to treatment. To our knowledge, this is the
      first case of BP associated with LAD reported in literature.

PMID- 19588061
TI  - Spontaneous pneumothorax in adulthood varicella.
AB  - Varicella is a generalized viral infection that is generally benign if it occurs
      in childhood, but it has a severe outcome in adulthood. Pneumonia is the main
      complication of adulthood varicella and may lead to respiratory failure.
      Spontaneous pneumothorax is a rarely reported complication during varicella in
      adult patients. Only one case of spontaneous pneumothorax associated with
      varicella pneumonia (VP) was published in 1990. We report a new case of
      pneumothorax in VP.

PMID- 19588062
TI  - Otitis externa and myringitis due to demodicidosis.
AB  - We report on an 84-year-old woman with chronic pruritic otitis externa and
      myringitis. Microbiological and mycological investigations failed to establish
      the cause, but histology revealed a large amount of Demodex mites. Topical
      treatment for this ectoparasite resulted in a complete remission. The myringitis
      was eventually treated successfully with myringoplasty. To the best of our
      knowledge this is the first case report on Demodex-induced otitis externa and
      myringitis.

PMID- 19588063
TI  - Impetigo herpetiformis with postpartum flare-up: a case report.
AB  - Impetigo herpetiformis is a rare dermatosis of pregnancy with typical onset
      during the last trimester of pregnancy and rapid resolution during the postpartum
      period. It is still a matter of debate whether it is a variant of pustular
      psoriasis or a separate entity. We report a case of impetigo herpetiformis with
      an earlier onset during the second trimester of pregnancy (G4 P2) and an atypical
      postpartum flare-up. Even though the case is not new per se, it reveals the
      natural course of this rare disease because the condition was neglected and given
      no oral treatment throughout the entire pregnancy. Consequently, the patient had
      a premature delivery with premature rupture of membranes, placental
      insufficiency, and intrauterine growth retardation.

PMID- 19588064
TI  - Self-inflicted non-healing genital ulcer: a rare form of factitious disorder.
AB  - Dermatitis artefacta is a factitious dermatological disorder with many forms of
      presentation that may occur on any part of the body. A diagnosis of dermatitis
      artefacta is often reached after rigorous and repeated investigations. Here we
      present the case of a 49-year-old single man complaining of a 4- month history of
      ulceration on the dorsal surface of the glans penis. In view of the unusual
      appearance of the lesion and the negative findings from clinical investigations,
      a diagnosis of dermatitis artefacta was made and the patient was referred for
      psychiatric evaluation. He was started on 20 mg/day of citalopram and titrated up
      to 40 mg/day by the 4th week, leading to complete remission in the following
      weeks. Thus, although rare, artefactual dermatitis should be considered in the
      differential diagnosis of unusual penile lesions.

PMID- 19588065
TI  - Toxicity assessment and clearance of Brazilian microbial pest control agents in
      mice.
AB  - The environmental toxicology of chemical pesticides have increased interest in
      the development and use of microbial pest control agents. In the present study
      four new Brazilian strains of Bacillus and one fungus were tested to evaluate the
      acute oral toxicity and clearance of these microbials in C57BL6 mice. No
      mortality was observed after exposure for any of the microorganisms tested.
      Clearance was significant after 30 days but for one strain of B. thuringiensis
      and one of B. sphaericus this time was not enough to completely eliminate the
      spores.

PMID- 19588066
TI  - Lethality toxicities induced by metal exposure during development in nematode
      Caenorhabditis elegans.
AB  - Lethality changes were investigated during development in 4 h metal exposed
      Caenorhabditis elegans. Exposure to examined metals caused severe lethality
      toxicities in L1- and L2-larvae, in L3-larvae exposed to examined metals at
      concentrations of 50 and 100 microM and to Pb, Hg, and Cr at the concentration of
      2.5 microM, in L4-larvae exposed to examined metals at concentrations of 50 and
      100 microM, and in adults exposed to Pb, Hg, and Cr at the concentration of 100
      microM. Moreover, the lethality toxicities induced by Pb and Hg in L1 larvae for
      4 h could be largely comparable to those in young adults for 24 h.

PMID- 19588067
TI  - Laparoscopic-assisted limited liver resection: technique, indications and
      results.
AB  - BACKGROUND/PURPOSE: The purpose of this work was to evaluate the short-term
      results of laparoscopic-assisted limited liver resection. METHODS: We analyzed
      the clinical outcome in 17 patients (mean age 70 +/- 8 years) who had undergone
      laparoscopic-assisted limited liver resection from March 2006 to December 2008.
      Preoperative diagnoses were HCC in 13 patients and metastasis of colon cancer in
      4. The operation consisted of laparoscopic mobilization of the target liver lobe,
      followed by open liver resection through a 7- to 10-cm extraction site. RESULTS:
      Mean tumor size was 3.0 +/- 1.1 cm (range 1.2-5 cm). The mean operative time was
      362 +/- 85 min. The mean blood loss was 451 +/- 413 ml, and no blood transfusion
      was required in any patient. There were no intraoperative complications, and
      conversion to laparotomy was needed in one case. Postoperative complications
      developed in 4 cases (4 infections, 24%), all of which were improved by
      conservative management. However, there was no postoperative mortality. None of
      the patients had any peritoneal carcinomatosis or port-site or resection site
      recurrence during a mean follow-up of 18 +/- 9.6 months. According to the
      analysis of the tumor location, the criterion for an adequate tumor location in
      the right lobe for this operation was set with the tumor at a distance of more
      than 5 cm from the inferior vena cava and the root of the hepatic vein (5 cm
      rule). CONCLUSION: Laparoscopic-assisted limited liver resection is feasible and
      well tolerated. Accumulation of more data may be needed for evaluation of long
      term outcome.

PMID- 19588069
TI  - Ruptured aneurysms of the choroidal branches of the posterior inferior cerebellar
      artery: a review of the literature and a case report.
AB  - Aneurysms of the choroidal branches of the posterior inferior cerebellar artery
      (PICA) are quite rare; only seven such cases have been reported thus far. In this
      study, we present a very rare case of a ruptured aneurysm of a choroidal branch
      of the PICA; the aneurysm was exposed by splitting the vermis and resected after
      proximal arterial ligation. We have also undertaken a thorough review of the
      literature on aneurysms in choroidal branches of the PICA, focusing on the
      clinical presentation, etiology, radiological findings, and surgical strategies.
      We found that the aneurysms in our patient and the aneurysms in seven published
      case reports were small, and frequently associated with vascular anomalies.
      Intraventricular hemorrhage (IVH) in the fourth ventricle was detected in all
      eight cases. The outcomes of surgical treatment were generally favorable,
      notwithstanding the high incidence of rebleeding after rupture of distal PICA
      aneurysms. The recognition of predominant fourth ventricular hemorrhage should
      raise the suspicion of the presence of an underlying aneurysm, and digital
      subtraction angiograms (DSAs) should be immediately obtained in order to detect
      small aneurysms of the choroidal branches of the PICA.

PMID- 19588070
TI  - Indocyanine green video-angiography as an aid to surgical treatment of spinal
      dural arteriovenous fistulae.
AB  - PURPOSE: To illustrate the use of indocyanine green (ICG) video-angiography to
      confirm abolition of spinal dural arteriovenous fistula (SDAVF) and preserve the
      normal vascular anatomy intraoperatively. METHODS: A 73-year-old woman presenting
      with progressive myelopathy was diagnosed with an SDAVF, where the origin of the
      fistula was in close proximity to the origin of the posterior spinal artery. ICG
      was injected intravenously. Using a filter on the microscope, dynamic filling of
      the abnormal vasculature was visualised. RESULTS: After applying a clip to the
      fistulous connection, we were able to see the successful interruption of the
      dural fistula, on-table in real time. CONCLUSION: ICG video angiography confirmed
      interruption of the fistula and preservation of the associated posterior spinal
      artery. We find the application of this relatively new technology has the
      potential to shorten operating times, gives additional reassurance of
      completeness of surgical treatment and preservation of normal spinal vasculature.

PMID- 19588068
TI  - Role of tryptophan 95 in substrate specificity and structural stability of
      Sulfolobus solfataricus alcohol dehydrogenase.
AB  - A mutant of the thermostable NAD(+)-dependent (S)-stereospecific alcohol
      dehydrogenase from Sulfolobus solfataricus (SsADH) which has a single
      substitution, Trp95Leu, located at the substrate binding pocket, was fully
      characterized to ascertain the role of Trp95 in discriminating between chiral
      secondary alcohols suggested by the wild-type SsADH crystallographic structure.
      The Trp95Leu mutant displays no apparent activity with short-chain primary and
      secondary alcohols and poor activity with aromatic substrates and coenzyme.
      Moreover, the Trp --> Leu substitution affects the structural stability of the
      archaeal ADH, decreasing its thermal stability without relevant changes in
      secondary structure. The double mutant Trp95Leu/Asn249Tyr was also purified to
      assist in crystallographic analysis. This mutant exhibits higher activity but
      decreased affinity toward aliphatic alcohols, aldehydes as well as NAD(+) and
      NADH compared to the wild-type enzyme. The crystal structure of the
      Trp95Leu/Asn249Tyr mutant apo form, determined at 2.0 A resolution, reveals a
      large local rearrangement of the substrate site with dramatic consequences. The
      Leu95 side-chain conformation points away from the catalytic metal center and the
      widening of the substrate site is partially counteracted by a concomitant change
      of Trp117 side chain conformation. Structural changes at the active site are
      consistent with the reduced activity on substrates and decreased coenzyme
      binding.

PMID- 19588071
TI  - Raising the ethical standards in neurosurgery.

PMID- 19588072
TI  - Supratentorial craniotomy complicated by an homolateral remote cerebellar
      hemorrhage and a controlateral perisylvian infarction: case report.
AB  - The authors present the case of a 49-year-old male patient with a right remote
      cerebellar hemorrhage and left perisylvian venous infarction complicating a right
      supratentorial craniotomy for temporal meningomia resection. These two events may
      result from a functional stenosis (due to perioperative brainstem sag) of the
      junction between the vein of Galen and the straight sinus. Remote cerebellar
      hemorrhage could then be explained by infarction in the territory of cerebellar
      veins emptying in the vein of Galen, and the left perisylvian infarction could be
      caused by venous infarction in the territory of a dominant superficial sylvian
      vein emptying in the basal vein. This hypothesis could shed light on the
      pathophysiology of remote cerebellar hemorrhage.

PMID- 19588073
TI  - A ventral intradural arachnoid cyst on the cervical spine in a child.

PMID- 19588074
TI  - Peduncular hallucinosis and cerebellar cognitive affective syndrome: letter to
      the editor.

PMID- 19588075
TI  - Different light-activated in-office bleaching systems: a clinical evaluation.
AB  - The aim of this clinical study was to evaluate the efficiency of in-office
      bleaching systems with different light sources for color change and possible side
      effects such as tooth sensitivity and gingival irritations. Forty healthy
      volunteers aged 18 years and older (average age 27.3 years), having all their
      natural healthy teeth in shade A3 or darker on the Vita shade guide, with no
      restorations on the buccal surfaces and no tooth sensitivity, participated in
      this study. Participants were randomly assigned to four groups of ten volunteers.
      Group 1 received bleaching without light activation (Opalescence Xtra Boost,
      Ultradent); group 2 received bleaching (Laser White 10, Biolase) with a diode
      laser (810 nm, 10 W/ Laser Smile, Biolase) activation; group 3 received bleaching
      treatment (Remewhite, Remedent) with a plasma arc lamp (400-490 nm, 2800
      mV/cm(2), Remecure CL15), and group 4 received bleaching with a light emitting
      diode (LED) lamp (By White accelerator, Ensodent) according to the manufacturers'
      recommendations. The shade was assessed with a classical Vita shade guide (Vita
      Zahnfabrik) and a digital spectrophotometer (Vita Easy Shade, Vident). The color
      of teeth was scored at baseline and 1 week after bleaching. Any side effects on
      teeth or gingiva was recorded by visual analog scale. Results were analyzed
      statistically, by one-way analysis of variance (ANOVA), Kruskal-Wallis, and Mann
      Whitney U tests with Bonferroni correction. All the bleaching techniques resulted
      in shade change. No significant differences were found in the color change among
      the four groups with shade guide assessment (P > 0.05), but spectrophotometer
      readings exhibited significant differences among the groups (P < 0.05). The
      overall shade change values expressed as DeltaL, Deltaa, Deltab, DeltaE for group
      2 was significantly higher than those for the other groups (P < 0.05). Group 2
      also showed lower tooth and gingival sensitivity scores than those of the other
      groups (P < 0.05). All techniques resulted in shade change. Although the shade
      guide evaluation did not exhibit any differences among the bleaching treatment
      groups, spectrophotometer readings showed different findings. The results
      obtained by the two methods of evaluation of shade change used in this study were
      different from each other. Bleaching with diode laser resulted in less tooth and
      gingival sensitivity than the other bleaching systems. CLINICAL RELEVANCE: in
      office bleaching systems used with or without light, lead to a shade change. As
      bleaching with diode laser resulted in less tooth and gingival sensitivity, it
      might be preferred among in-office bleaching systems.

PMID- 19588076
TI  - The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine
      oxidase.
AB  - Semicarbazide-sensitive amine oxidases (SSAOs) catalyze oxidative deamination of
      primary amines, but the true physiological function of these enzymes is still
      poorly understood. Here, we have studied the functional and structural
      characteristics of a human cell-surface SSAO, AOC2, which is homologous to the
      better characterized family member, AOC3. The preferred in vitro substrates of
      AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of
      methylamine and benzylamine, the favored substrates of AOC3. Molecular modeling
      suggested structural differences between AOC2 and AOC3, which provide AOC2 with
      the capability to use the larger monoamines as substrates. Even though AOC2 mRNA
      was expressed in many tissues, the only tissues with detectable AOC2-like enzyme
      activity were found in the eye. Characterization of AOC2 will help in evaluating
      the contribution of this enzyme to the pathological processes attributed to the
      SSAO activity and in designing specific inhibitors for the individual members of
      the SSAO family.

PMID- 19588078
TI  - Evaluation of toxic elements in scalp hair samples of myocardial infarction
      patients at different stages as related to controls.
AB  - In the present study, the association of arsenic, cadmium, lead, and nickel
      between scalp hair samples and mortality from myocardial infarction (MI) patients
      at first, second, and third heart attack was studied. The biological samples of
      130 MI patients (77 male and 53 female) age ranged (45-60 years), were collected
      and 61 healthy persons of same age group (33 male and 28 female) was selected as
      control subjects. The toxic elements (TEs) in biological samples were assessed by
      the electrothermal atomic absorption spectrophotometry prior to microwave
      assisted acid digestion. The validity of methodology was checked by the certified
      human hair reference material (BCR 397). It was observed during the study that
      78% of 32 patients of the third MI, age >50 years were expired. In these
      subjects, the level of As, Cd, Ni, and Pb were increased by 10.6%, 19.5%, 15.7%,
      and 9.8% in the scalp hair as compared to those who tolerated third MI attack (p
      = 0.12). The high level of toxic metals may play a role in the development of
      heart disease in the subjects of this study.

PMID- 19588077
TI  - Sympathetic ophthalmia following vitreoretinal surgery.
AB  - The objective is to discuss the characteristics of three patients who developed
      sympathetic ophthalmia following vitreoretinal surgery. The first case was a 29
      year-old man who underwent placement of an encircling band, pars plana
      vitrectomy, foreign body removal, endolaser photocoagulation, transscleral
      cryotherapy, and silicone oil injection due to a retained foreign body 3 months
      after a corneoscleral rupture repair. He experienced visual loss in the fellow
      eye 2 months after the vitrectomy. An extensive exudative detachment was detected
      in the fellow eye. Sympathetic ophthalmia was diagnosed and systemic steroids
      together with azathioprine were initiated. The injured eye was enucleated as
      there was no useful vision. The other two cases were operated for rhegmatogenous
      retinal detachments. One underwent placement of an encircling band, pars plana
      vitrectomy, silicone oil injection, and endolaser photocoagulation with good
      anatomic outcome. However, 4 months later, the fellow eye experienced severe
      visual loss with disc swelling and hyperemia and exudative retinal detachment.
      Systemic steroid was sufficient to reverse the process and the visual acuity
      recovered. The other case underwent placement of an encircling band, subretinal
      fluid drainage, SF(6) injection and 360 degrees indirect laser photocoagulation.
      Two years later, he noted a sudden visual decrease in the fellow eye in which we
      detected a Harada-like extensive exudative detachment. Systemic steroid without
      immunosuppressive therapy rendered regression of the detachment and recovery of
      good visual acuity. Sympathetic ophthalmia may occur following vitreoretinal
      surgery either for trauma-related problems or rhegmatogenous retinal detachment.
      Since it may present with relatively mild anterior segment findings and mainly
      posterior segment involvement; any visual disturbance in the fellow eye of a
      patient with a history of perforating trauma or vitreoretinal surgery should be
      thoroughly evaluated for sympathetic ophthalmia.

PMID- 19588079
TI  - Trace Element Studies on Tinospora cordifolia (Menispermaceae), Ocimum sanctum
      (Lamiaceae), Moringa oleifera (Moringaceae), and Phyllanthus niruri
      (Euphorbiaceae) Using PIXE.
AB  - Traditionally, Tinospora cordifolia (Willd.) Hook. F. & Thomson (Menispermaceae),
      Ocimum sanctum L. (Lamiaceae), Moringa oleifera Lam. (Moringaceae), and
      Phyllanthus niruri L. (Euphorbiaceae) are some of the commonly used medicinal
      plants in India for curing ailments ranging from common cold, skin diseases, and
      dental infections to major disorders like diabetes, hypertension, jaundice,
      rheumatism, etc. To understand and correlate their medicinal use, trace element
      studies on the aqueous extract of these medicinal plants have been carried out
      using particle-induced X-ray emission technique. A 2-MeV proton beam was used to
      identify and characterize major and minor elements namely Cl, K, Ca, Ti, Cr, Mn,
      Fe, Co, Ni, Cu, Zn, Br, and Sr in them. Results have revealed that these elements
      are present in varying concentrations in the selected plants. Notable results
      include very high concentrations of Cl, K, and Ca in all the leaf samples,
      appreciable levels of Mn in all plants, high Zn content in T. cordifolia, and the
      aqueous extract of Moringa leaves compared to others and relative higher
      concentrations of Cr in all the plants.

PMID- 19588080
TI  - [Satisfaction of dysphonic patients with psychosomatic assessment and
      intervention].
AB  - BACKGROUND: Comorbid physical and psychological complaints are more common in
      patients with dysphonia than in the general population. In a prospective
      randomized study the effects of structured psychosomatic diagnostics and verbal
      intervention on the satisfaction of patients with dysphonia were investigated.
      MATERIALS AND METHODS: A total of 54 dysphonic patients (33 women, 21 men, age
      51.1+/-16.4 years) with dysphonia (organic n=36, functional n=18) were examined
      and their subjective experiences were collected by the following psychometric
      questionnaires: voice-related quality of life (VRQOL), hospital anxiety and
      depression scale (HADS-D) and the "Giessener Beschwerdebogen" (Giessen
      questionnaire on physical complaints GBB). Patients were randomized into 2
      groups: group 1 (n=27) filled in the questionnaires and the answers were reviewed
      within the medical consultation. This was followed by an interview on patient
      satisfaction. In the control group 2 (n=27) a medical examination and
      consultation were carried out and then questioned on patient satisfaction. The
      psychometric questionnaires were completed by the patients shortly before leaving
      the department. RESULTS: The study group 1 was significantly more satisfied than
      group 2 on different statistic levels according to the items compared.
      CONCLUSIONS: Patients suffering from dysphonia are positively influenced with
      respect to patient satisfaction by a structured psychosomatic diagnostic and
      intervention.

PMID- 19588081
TI  - Pompe disease in a Brazilian series: clinical and molecular analyses with
      identification of nine new mutations.
AB  - Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an
      inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with
      predominant manifestations of skeletal muscle weakness. A broad range of studies
      have been published focusing on Pompe patients from different countries, but none
      from Brazil. We investigated 41 patients with either infantile-onset (21 cases)
      or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA
      gene mutation screening. Molecular analyses identified 71 mutant alleles from the
      probands, nine of which are novel (five missense mutations c.136T > G, c.650C >
      T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A >
      G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G >
      T). Interestingly, the c.1905C > A variant was detected in four unrelated
      patients and may represent a common Brazilian Pompe mutation. The c.2560C > T
      severe mutation was frequent in our population suggesting a high prevalence in
      Brazil. Also, eight out of the 21 infantile-onset patients have two truncating
      mutations predicted to abrogate protein expression. Of the ten late-onset
      patients who do not carry the common late-onset intronic mutation c.-32-13T > G,
      five (from three separate families) carry the recently described intronic
      mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation
      c.1781G > C in combination with known severe mutation c.1941C > G. The
      association of these variants (c.1781G > C and c.-32-3C > A) with late-onset
      disease suggests that they allow for some residual activity in these patients.
      Our findings help to characterize Pompe disease in Brazil and support the need
      for additional studies to define the wide clinical and pathological spectrum
      observed in this disease.

PMID- 19588082
TI  - The state-of-the-art of chromatin immunoprecipitation.
AB  - The biological significance of interactions of nuclear proteins with DNA in the
      context of gene expression, cell differentiation, or disease has immensely been
      enhanced by the advent of chromatin immunoprecipitation (ChIP). ChIP is a
      technique whereby a protein of interest is selectively immunoprecipitated from a
      chromatin preparation to determine the DNA sequences associated with it. ChIP has
      been widely used to map the localization of post-translationally modified
      histones, histone variants, transcription factors, or chromatin-modifying enzymes
      on the genome or on a given locus. In spite of its power, ChIP has for a long
      time remained a cumbersome procedure requiring large number of cells. These
      limitations have sparked the development of modifications to shorten the
      procedure, simplify the sample handling, and make the ChIP amenable to small
      number of cells. In addition, the combination of ChIP with DNA microarray, paired
      end ditag, and high-throughput sequencing technologies has in recent years
      enabled the profiling of histone modifications and transcription factor occupancy
      on a genome-wide scale. This review highlights the variations on the theme of the
      ChIP assay, the various detection methods applied downstream of ChIP, and
      examples of their application.

PMID- 19588083
TI  - Characterization and quality control of antibodies used in ChIP assays.
AB  - We present here the very robust characterization and quality control (QC) process
      that we have established for our polyclonal antibodies, which are mainly directed
      against targets relevant to the epigenetics field such as modified histones,
      modifying enzymes, and chromatin-interacting proteins. The final purpose of the
      characterization and QC is to label antibodies as chromatin immunoprecipitation
      (ChIP) grade. Indeed, the ChIP method is extensively used in epigenetics to study
      gene regulation and relies on the use of antibodies to select the protein of
      interest and then precipitate and identify the DNA associated to it. We have
      optimized in-house all protocols and reagents needed from the first to the last
      step of antibody characterization. First, following immunizations, the rabbit
      crude serum is tested for immune response. Whether or not the antibody is
      specific is determined in further characterizations. Then, only specific
      antibodies are tested in ChIP using an optimized method which is ideal for
      antibody screening. Once QC is established for one antibody, it is used to
      similarly characterize each antibody batch in order to supply researchers in a
      reproducible manner with validated antibodies. All in all, this demonstrates that
      we develop epigenetics research tools based on everyday's researcher's needs by
      providing batch-specific fully characterized ChIP-grade antibodies.

PMID- 19588084
TI  - The fast chromatin immunoprecipitation method.
AB  - The chromatin immunoprecipitation assay (ChIP assay) has greatly facilitated the
      recent, dramatic expansion of our knowledge of the protein-DNA interactions
      involved in regulating gene expression, DNA repair, and cell division. The power
      of the assay is that it gives a researcher the ability to not only detect a
      specific protein-DNA interaction in vivo but also determine the relative density
      of factors along genes or the entire genome. Though powerful, the traditional
      assay is time consuming (involving 2 days or more) and laborious. With Fast ChIP,
      we simplified the assay to greatly reduce the time and labor involved. The
      improved assay is especially useful for studies which involve many samples,
      including the probing of multiple chromatin factors simultaneously and/or looking
      at genomic events over several time points. Using Fast ChIP, 24 sheared chromatin
      samples can be processed to yield PCR-ready DNA in 5 h.

PMID- 19588085
TI  - MicroChIP: chromatin immunoprecipitation for small cell numbers.
AB  - Chromatin immunoprecipitation (ChIP) is a technique of choice for studying
      protein-DNA interactions. ChIP has been used for mapping the location of modified
      histones on DNA, often in relation to transcription or differentiation.
      Conventional ChIP protocols, however, require large number of cells, which limits
      the applicability of ChIP to rare cell samples. ChIP assays for small cell
      numbers (in the range of 10,000-100,000) have been recently reported; however,
      these remain lengthy. Our laboratory has elaborated fast ChIP assays suitable for
      small cell numbers (100-100,000) and for the immunoprecipitation of histone
      proteins or transcription factors under cross-linking conditions. We describe
      here a rapid micro (micro)ChIP assay suited for multiple parallel ChIPs from a
      single chromatin batch from 1,000 cells. The assay is also applicable to a single
      immunoprecipitation from 100 cells.

PMID- 19588086
TI  - Fish'n ChIPs: chromatin immunoprecipitation in the zebrafish embryo.
AB  - Chromatin immunoprecipitation (ChIP) is arguably the assay of choice to determine
      the genomic localization of DNA- or chromatin-binding proteins, including post
      translationally modified histones, in cells. The increasing importance of the
      zebrafish, Danio rerio, as a model organism in functional genomics has recently
      sparked investigations of ChIP-based genome-scale mapping of modified histones on
      promoters, and studies on the role of specific transcription factors in
      developmental processes. ChIP assays used in these studies are cumbersome and
      conventionally require relatively large number of embryos. To simplify the
      procedure and to be able to apply the ChIP assay to reduced number of embryos, we
      re-evaluated the protocol for preparation of embryonic chromatin destined to
      ChIP. We found that manual homogenization of embryos rather than protease
      treatment to remove the chorion enhances ChIP efficiency and quickens the assay.
      We also incorporated key steps from a recently published ChIP assay for small
      cell numbers. We report here a protocol for immunoprecipitation of modified
      histones from mid-term blastula zebrafish embryos.

PMID- 19588088
TI  - Flow cytometric and laser scanning microscopic approaches in epigenetics
      research.
AB  - Our understanding of epigenetics has been transformed in recent years by the
      advance of technological possibilities based primarily on a powerful tool,
      chromatin immunoprecipitation (ChIP). However, in many cases, the detection of
      epigenetic changes requires methods providing a high-throughput (HTP) platform.
      Cytometry has opened a novel approach for the quantitative measurement of
      molecules, including PCR products, anchored to appropriately addressed microbeads
      (Pataki et al. 2005. Cytometry 68, 45-52). Here we show selected examples for the
      utility of two different cytometry-based platforms of epigenetic analysis: ChIP
      on-beads, a flow-cytometric test of local histone modifications (Szekvolgyi et
      al. 2006. Cytometry 69, 1086-1091), and the laser scanning cytometry-based
      measurement of global epigenetic modifications that might help predict clinical
      behavior in different pathological conditions. We anticipate that such
      alternative tools may shortly become indispensable in clinical practice,
      translating the systematic screening of epigenetic tags from basic research into
      routine diagnostics of HTP demand.

PMID- 19588087
TI  - Epitope tagging of endogenous proteins for genome-wide chromatin
      immunoprecipitation analysis.
AB  - The development of chromatin immunoprecipitation methods coupled with DNA
      microarray (ChIP-chip) technology has enabled genome-wide identification of cis
      DNA regulatory elements to which transcription factors bind. Nonetheless, the
      ChIP-chip technology requires antibodies with extremely high affinity and
      specificity for the target transcription factors. Unfortunately, such antibodies
      are not available for most human transcription factors. In principle, this
      problem can be circumvented by utilizing ectopically expressed epitope-tagged
      proteins recognizable by well-characterized antibodies. However, such expression
      is no longer endogenous. To surmount this problem, we have successfully developed
      a facile method to knock in a 3xFlag epitope into the endogenous gene loci of
      transcription factors. The knock-in approach provides a general solution for the
      study of proteins for which antibodies are substandard or not available.

PMID- 19588089
TI  - Serial analysis of binding elements for transcription factors.
AB  - The ability to determine genome-wide location of transcription factor binding
      sites (TFBS) is crucial for elucidating gene regulatory networks in human cells
      during normal development and disease such as tumorigenesis. To achieve this
      goal, we developed a method called serial analysis of binding elements for
      transcription factors (SABE) for globally identifying TFBS in human or other
      mammalian genomes. In this method, a specific antibody targeting a DNA-binding
      transcription factor of interest is used to pull down the transcription factor
      and its bound DNA elements through chromatin immunoprecipitation (ChIP). ChIP DNA
      fragments are further enriched by subtractive hybridization against non-enriched
      DNA and analyzed through generation of sequence tags similar to serial analysis
      of gene expression (SAGE). The SABE method circumvents the need for microarrays
      and is able to identify immunoprecipitated loci in an unbiased manner. The
      combination of ChIP, subtractive hybridization, and SAGE-type methods is
      advantageous over other similar strategies to reduce the level of intrinsic noise
      sequences that is typically present in ChIP samples from human or other mammalian
      cells.

PMID- 19588090
TI  - Modeling and analysis of ChIP-chip experiments.
AB  - Chromatin immunoprecipitation on microarrays, also known as ChIP-chip, is a
      popular technique for genome-wide localization of DNA-binding proteins. However,
      the high density (several million genomic sequences for small eukaryote genomes)
      and the high noise-to-signal ratio of microarrays make the analysis of ChIP-chip
      data very challenging. In this chapter, we review some of the issues involved in
      the analysis of ChIP-chip data and present a few statistical methods that can be
      used to overcome these issues and improve the detection of DNA-protein binding
      sites.

PMID- 19588091
TI  - Use of SNP-arrays for ChIP assays: computational aspects.
AB  - The simultaneous genotyping of thousands of single nucleotide polymorphisms
      (SNPs) in a genome using SNP-Arrays is a very important tool that is
      revolutionizing genetics and molecular biology. We expanded the utility of this
      technique by using it following chromatin immunoprecipitation (ChIP) to assess
      the multiple genomic locations protected by a protein complex recognized by an
      antibody. The power of this technique is illustrated through an analysis of the
      changes in histone H4 acetylation, a marker of open chromatin and
      transcriptionally active genomic regions, which occur during differentiation of
      human myoblasts into myotubes. The findings have been validated by the
      observation of a significant correlation between the detected histone
      modifications and the expression of the nearby genes, as measured by DNA
      expression microarrays. This chapter focuses on the computational analysis of the
      data.

PMID- 19588092
TI  - DamID: a methylation-based chromatin profiling approach.
AB  - Gene expression is a dynamic process and is tightly connected to changes in
      chromatin structure and nuclear organization (Schneider, R. and Grosschedl, R.,
      2007, Genes Dev. 21, 3027-3043; Kosak, S. T. and Groudine, M., 2004, Genes Dev.
      18, 1371-1384). Our ability to understand the intimate interactions between
      proteins and the rapidly changing chromatin environment requires methods that
      will be able to provide accurate, sensitive, and unbiased mapping of these
      interactions in vivo (van Steensel, B., 2005, Nat. Genet. 37 Suppl, S18-24). One
      such tool is DamID chromatin profiling, a methylation-based tagging method used
      to identify the direct genomic loci bound by sequence-specific transcription
      factors, co-factors as well as chromatin- and nuclear-associated proteins genome
      wide (van Steensel, B. and Henikoff, S., 2000, Nat. Biotechnol. 18, 424-428; van
      Steensel, Delrow, and Henikoff, 2001, Nat. Genet. 27, 304-308). Combined with
      other functional genomic methods and bioinformatics analysis (such as expression
      profiles and 5C analysis), DamID emerges as a powerful tool for analysis of
      chromatin structure and function in eukaryotes. DamID allows the detection of the
      direct genomic targets of any given factor independent of antibodies and without
      the need for DNA cross-linking. It is highly valuable for mapping proteins that
      associate with the genome indirectly or loosely (e.g., co-factors). DamID is
      based on the ability to fuse a bacterial Dam-methylase to a protein of interest
      and subsequently mark the factor's genomic binding site by adenine methylation.
      This marking is simple, highly specific, sensitive, inert, and can be done in
      both cell culture and living organisms. Below is a short description of the
      method, followed by a step-by-step protocol for performing DamID in Drosophila
      cells and embryos. Due to space limitations, the reader is referred to recent
      reviews that compare the method with other profiling techniques such as ChIP-chip
      as well as protocols for performing DamID in mammalian cells (NSouthall, T. D.
      and Brand, A. H., 2007, Nat. Struct. Mol. Biol. 14, 869-871; Orian, A., 2006,
      Curr. Opin. Genet. Dev. 16, 157-164; Vogel, M. J., Peric-Hupkes, D. and van
      Steensel, B. 2007, Nat. Protoc. 2, 1467-1478).

PMID- 19588093
TI  - Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification.
AB  - Chromosome conformation capture (3C) methodology was developed to study spatial
      organization of long genomic regions in living cells. Briefly, chromatin is fixed
      with formaldehyde in vivo to cross-link interacting sites, digested with a
      restriction enzyme and ligated at a low DNA concentration so that ligation
      between cross-linked fragments is favored over ligation between random fragments.
      Ligation products are then analyzed and quantified by PCR. So far, semi
      quantitative PCR methods were widely used to estimate the ligation frequencies.
      However, it is often important to estimate the ligation frequencies more
      precisely which is only possible by using the real-time PCR. At the same time, it
      is equally necessary to monitor the specificity of PCR amplification. That is why
      the real-time PCR with TaqMan probes is becoming more and more popular in 3C
      studies. In this chapter, we describe the general protocol for 3C analysis with
      the subsequent estimation of ligation frequencies by using the real-time PCR
      technology with TaqMan probes. We discuss in details all steps of the
      experimental procedure paying special attention to weak points and possible ways
      to solve the problems. A special attention is also paid to the problems in
      interpretation of the results and necessary control experiments. Besides, in
      theory, we consider other approaches to analysis of the ligation products used in
      frames of the so-called 4C and 5C methods. The recently developed chromatin
      immunoprecipitation (ChIP)-loop assay representing a combination of 3C and ChIP
      is also discussed.

PMID- 19588094
TI  - Determining spatial chromatin organization of large genomic regions using 5C
      technology.
AB  - Spatial organization of chromatin plays an important role at multiple levels of
      genome regulation. On a global scale, its function is evident in processes like
      metaphase and chromosome segregation. On a detailed level, long-range
      interactions between regulatory elements and promoters are essential for proper
      gene regulation. Microscopic techniques like FISH can detect chromatin contacts,
      although the resolution is generally low making detection of enhancer-promoter
      interaction difficult. The 3C methodology allows for high-resolution analysis of
      chromatin interactions. 3C is now widely used and has revealed that long-range
      looping interactions between genomic elements are widespread. However, studying
      chromatin interactions in large genomic regions by 3C is very labor intensive.
      This limitation is overcome by the 5C technology. 5C is an adaptation of 3C, in
      which the concurrent use of thousands of primers permits the simultaneous
      detection of millions of chromatin contacts. The design of the 5C primers is
      critical because this will determine which and how many chromatin interactions
      will be examined in the assay. Starting material for 5C is a 3C template. To make
      a 3C template, chromatin interactions in living cells are cross-linked using
      formaldehyde. Next, chromatin is digested and subsequently ligated under
      conditions favoring ligation events between cross-linked fragments. This yields a
      genome-wide 3C library of ligation products representing all chromatin
      interactions in vivo. 5C then employs multiplex ligation-mediated amplification
      to detect, in a single assay, up to millions of unique ligation products present
      in the 3C library. The resulting 5C library can be analyzed by microarray
      analysis or deep sequencing. The observed abundance of a 5C product is a measure
      of the interaction frequency between the two corresponding chromatin fragments.
      The power of the 5C technique described in this chapter is the high-throughput,
      high-resolution, and quantitative way in which the spatial organization of
      chromatin can be examined.

PMID- 19588095
TI  - Analysis of nascent RNA transcripts by chromatin RNA immunoprecipitation.
AB  - Biochemical methods to analyze co-transcriptional recruitment of co-activators to
      nascent RNA molecules have lagged behind for many years. Most of the information
      on co-transcriptional regulation of nascent RNA came from invaluable in situ
      studies using single-cell model systems. More recently, the chromatin RNA
      immunoprecipitation technique has been developed to evaluate at the molecular
      level the association of proteins with nascent RNA which is still coupled to
      chromatin. Similar to chromatin immunoprecipitation, the chromatin RNA
      immunoprecipitation method is suitable to study events along specific genes, and
      it has been successfully used in numerous applications to demonstrate the cross
      talk between transcription and RNA processing. This technique has a considerable
      margin of technological development especially in high-throughput screening
      experiments in combination with microarrays. In this chapter, we describe a RIP
      protocol optimized in our laboratory to study association of RNA binding proteins
      with specific nascent mRNA transcripts.

PMID- 19588096
TI  - Methyl DNA immunoprecipitation.
AB  - Epigenetics is the study of heritable changes in gene expression. Chromatin
      immunoprecipitation (ChIP) and methylation status analysis of genes have been
      applied to the study of epigenetic modifications, often perturbed in human
      cancer. ChIP is a technique allowing the analysis of the protein association with
      specific genomic regions in the context of intact cells. ChIP and
      immunoprecipitation (IP) of methylated DNA, both rely on the use of well
      characterized specific antibodies. The first is described in Chapter 2 and the
      second is shown here. At Diagenode, a novel METHYL kit has been designed to
      immunoprecipitate methylated DNA (Methyl DNA IP). This kit allows you to perform
      DNA methylation analysis of your sample together with optimized internal IP
      controls, all in one tube. This brand new Methyl DNA IP method provides
      methylated DNA (meDNA) and unmethylated DNA (unDNA) controls to be used together
      with your DNA sample, allowing direct correlation between immunoprecipitated
      material and methylation status. Such methylation analysis is highly specific and
      each IP is quality controlled, two essential keys for reliable results. In
      addition, the kit protocol is fast and user-friendly.

PMID- 19588097
TI  - Immunoprecipitation of methylated DNA.
AB  - DNA methylation contributes to the regulation of long-term gene repression by
      enabling the recruitment of transcriptional repressor complexes to methylated
      cytosines. Several methods for detecting DNA methylation at the gene-specific and
      genome-wide levels have been developed. Methylated DNA immunoprecipitation, or
      MeDIP, consists of the selective immunoprecipitation of methylated DNA fragments
      using antibodies to 5-methylcytosine. The genomic site of interest can be
      detected by PCR, hybridization to DNA arrays, or by direct sequencing. This
      chapter describes the MeDIP protocol and quality control tests that should be
      performed throughout the procedure.

PMID- 19588098
TI  - Gene-specific and genome-wide ChIP approaches to study plant transcriptional
      networks.
AB  - Chromatin immunoprecipitation (ChIP) provides a versatile tool to investigate the
      in vivo location of DNA-binding proteins on genomic DNA. ChIP approaches are
      gaining significance in plants, in cases when entire genome sequences are
      available (e.g., Arabidopsis), for which several high-density oligo arrays have
      been or are being developed. Nevertheless, plant ChIP and ChIP-chip still present
      some technical challenges. Here, we describe general methods for ChIP and ChIP
      chip, which have been successfully applied to maize and Arabidopsis.

PMID- 19588099
TI  - Genome-wide analysis of RNA-protein interactions in plants.
AB  - RNA-protein interactions profoundly impact organismal development and function
      through their contributions to the basal gene expression machineries and their
      regulation of post-transcriptional processes. The repertoire of predicted RNA
      binding proteins (RBPs) in plants is particularly large, suggesting that the RNA
      protein interactome in plants may be more complex and dynamic even than that in
      metazoa. To dissect RNA-protein interaction networks, it is necessary to identify
      the RNAs with which each RBP interacts and to determine how those interactions
      influence RNA fate and downstream processes. Identification of the native RNA
      ligands of RBPs remains a challenge, but several high-throughput methods for the
      analysis of RNAs that copurify with specific RBPs from cell extract have been
      reported recently. This chapter reviews approaches for defining the native RNA
      ligands of RBPs on a genome-wide scale and provides a protocol for a method that
      has been used to this end for RBPs that localize to the chloroplast.

PMID- 19588100
TI  - Whole-genome microarrays: applications and technical issues.
AB  - DNA microarrays have become a mainstream tool in experimental plant biology. The
      constant improvements in the technological platforms have enabled the development
      of the tiling DNA microarrays that cover the whole genome, which in turn
      catalyzed the wide variety of creative applications of such microarrays in the
      areas as diverse as global studies of genetic variation, DNA-binding proteins,
      DNA methylation, and chromatin and transcriptome dynamics. This chapter attempts
      to summarize such applications as well as discusses some technical and strategic
      issues that are particular to the use of tiling microarrays.

PMID- 19588101
TI  - Manipulating large-scale Arabidopsis microarray expression data: identifying
      dominant expression patterns and biological process enrichment.
AB  - A series of large-scale Arabidopsis thaliana microarray expression experiments
      profiling genome-wide expression across different developmental stages, cell
      types, and environmental conditions have resulted in tremendous amounts of gene
      expression data. This gene expression is the output of complex transcriptional
      regulatory networks and provides a starting point for identifying the dominant
      transcriptional regulatory modules acting within the plant. Highly co-expressed
      groups of genes are likely to be regulated by similar transcription factors.
      Therefore, finding these co-expressed groups can reduce the dimensionality of
      complex expression data into a set of dominant transcriptional regulatory
      modules. Determining the biological significance of these patterns is an
      informatics challenge and has required the development of new methods. Using
      these new methods we can begin to understand the biological information contained
      within large-scale expression data sets.

PMID- 19588102
TI  - Applications of ultra-high-throughput sequencing.
AB  - The genomics era has enabled scientists to more readily pose truly global
      questions regarding mutation, evolution, gene and genome structure, function, and
      regulation. Just as Sanger sequencing ushered in a paradigm shift that enabled
      the molecular basis of biological questions to be directly addressed, to an even
      greater degree, ultra-high-throughput DNA sequencing is poised to dramatically
      change the nature of biological research. New sequencing technologies have opened
      the door for novel questions to be addressed at the level of the entire genome in
      the areas of comparative genomics, systems biology, metagenomics, and genome
      biology. These new sequencing technologies provide a tremendous amount of DNA
      sequence data to be collected at an astounding pace, with reduced costs, effort,
      and time as compared to Sanger sequencing. Applications of ultra-high-throughput
      sequencing (UHTS) are essentially limited only by the imaginations of
      researchers, and include genome sequencing/resequencing, small RNA discovery,
      deep SNP discovery, chromatin immunoprecipitation (ChIP) and RNA
      immunoprecipitation (RIP) coupled with sequence identification, transcriptome
      analysis including empirical annotation, discovery and characterization of
      alternative splicing, and gene expression profiling. This technology will have a
      profound impact on plant breeding, biotechnology, and our fundamental
      understanding of plant evolution, development, and environmental responses. In
      this chapter, we provide an overview of UHTS approaches and their applications.
      We also describe a protocol we have developed for deep sequencing of plant
      transcriptomes using the Illumina/Solexa sequencing platform.

PMID- 19588103
TI  - Isolation of plant polysomal mRNA by differential centrifugation and ribosome
      immunopurification methods.
AB  - Polyribosomes (polysomes) form as multiple ribosomes engage in translation on a
      single mRNA. This process is regulated for individual mRNAs by both development
      and the environment. To evaluate the translation state of an mRNA, ribosomal
      subunits, ribosomes, and polysomes can be isolated from detergent-treated cell
      extracts by high-speed differential centrifugation. These ribonucleoprotein
      complexes can be further purified by centrifugation through sucrose density
      gradients. By fractionation of the gradient the amount of an individual mRNA in a
      sub-population of polysomes can be quantitatively determined. Here, we describe
      methods for the isolation and quantification of polysome complexes from plant
      tissues. The mRNA obtained can be further analyzed by methods that evaluate
      polysomal mRNA abundance at the individual transcript or global level. A
      modification of the conventional polysome isolation procedure is described for
      transgenic Arabidopsis thaliana that express an epitope-tagged version of
      ribosomal protein L18 (RPL18) that facilitates capture of ribosomes from crude
      cell extracts by a one-step immunoprecipitation method.

PMID- 19588104
TI  - Chromatin charting: global mapping of epigenetic effects.
AB  - To tackle the question of how chromatin organization is involved in global
      regulation of genome-related processes such as transcription, we have recently
      created a collection of 277 transposon-tagged Arabidopsis lines comprised of a
      single insert with a common luciferase reporter cassette and a LacO repeat array
      for visual tracking of the tagged region via fluorescent protein fusion
      technology. Using this collection of plants, one can begin to map transgene
      position effects as well as global epigenetic control in response to
      developmental or externally applied cues. In this chapter, we will outline the
      approach and methods for deploying this novel resource for the study of global
      gene control, using Arabidopsis as a convenient model system.

PMID- 19588105
TI  - Clone-based functional genomics.
AB  - Annotated genomes have provided a wealth of information about gene structure and
      gene catalogs in a wide range of species. Taking advantage of these developments,
      novel techniques have been implemented to investigate systematically diverse
      aspects of gene and protein functions underpinning biology processes. Here, we
      review functional genomics applications that require the mass production of
      cloned sequence repertoires, including ORFeomes and silencing tag collections. We
      discuss the techniques employed in large-scale cloning projects and we provide an
      up-to-date overview of the clone resources available for model plant species and
      of the current applications that may be scaled up for systematic plant gene
      studies.

PMID- 19588106
TI  - Challenges and approaches to statistical design and inference in high-dimensional
      investigations.
AB  - Advances in modern technologies have facilitated high-dimensional experiments
      (HDEs) that generate tremendous amounts of genomic, proteomic, and other "omic"
      data. HDEs involving whole-genome sequences and polymorphisms, expression levels
      of genes, protein abundance measurements, and combinations thereof have become a
      vanguard for new analytic approaches to the analysis of HDE data. Such situations
      demand creative approaches to the processes of statistical inference, estimation,
      prediction, classification, and study design. The novel and challenging
      biological questions asked from HDE data have resulted in many specialized
      analytic techniques being developed. This chapter discusses some of the unique
      statistical challenges facing investigators studying high-dimensional biology and
      describes some approaches being developed by statistical scientists. We have
      included some focus on the increasing interest in questions involving testing
      multiple propositions simultaneously, appropriate inferential indicators for the
      types of questions biologists are interested in, and the need for replication of
      results across independent studies, investigators, and settings. A key
      consideration inherent throughout is the challenge in providing methods that a
      statistician judges to be sound and a biologist finds informative.

PMID- 19588107
TI  - Discrete dynamic modeling with asynchronous update, or how to model complex
      systems in the absence of quantitative information.
AB  - A major aim of systems biology is the study of the inter-relationships found
      within and between large biological data sets. Here we describe one systems
      biology method, in which the tools of network analysis and discrete dynamic
      (Boolean) modeling are used to develop predictive models of cellular signaling in
      cases where detailed temporal and kinetic information regarding the propagation
      of the signal through the system is lacking. This approach is also applicable to
      data sets derived from some other types of biological systems, such as
      transcription factor-mediated regulation of gene expression during the control of
      developmental fate, or host defense responses following pathogen attack, and is
      equally applicable to plant and non-plant systems. The method also allows
      prediction of how elimination of one or more individual signaling components will
      affect the ultimate outcome, thus allowing the researcher to model the effects of
      genetic knockout or pharmacological block. The method also serves as a starting
      point from which more quantitative models can be developed as additional
      information becomes available.

PMID- 19588108
TI  - Quantification of variation in expression networks.
AB  - Gene expression microarrays allow rapid and easy quantification of transcript
      accumulation for almost transcripts present in a genome. This technology has been
      utilized for diverse investigations from studying gene regulation in response to
      genetic or environmental fluctuation to global expression QTL (eQTL) analyses of
      natural variation. Typical analysis techniques focus on responses of individual
      genes in isolation of other genes. However, emerging evidence indicates that
      genes are organized into regulons, i.e., they respond as groups due to individual
      transcription factors binding multiple promoters, creating what is commonly
      called a network. We have developed a set of statistical approaches that allow
      researchers to test specific network hypothesis using a priori-defined gene
      networks. When applied to Arabidopsis thaliana this approach has been able to
      identify natural genetic variation that controls networks. In this chapter we
      describe approaches to develop and test specific network hypothesis utilizing
      natural genetic variation. This approach can be expanded to facilitate direct
      tests of the relationship between phenotypic trait and transcript genetic
      architecture. Finally, the use of a priori network definitions can be applied to
      any microarray experiment to directly conduct hypothesis testing at a genomics
      level.

PMID- 19588109
TI  - Co-expression analysis of metabolic pathways in plants.
AB  - Co-expression analysis allows experimenters to re-use archived expression
      microarray data to uncover previously unknown functional relationships between
      genes. An observation that a group of genes are co-expressed across diverse
      experimental conditions suggests they may play similar roles in the cell. Several
      thousand expression microarray experiments performed on samples from Arabidopsis
      thaliana have entered the public domain and it is now possible to use these data
      to investigate metabolic networks in plants. This chapter explains how to use a
      Web-based tool (CressExpress) to investigate co-expression of genes involved in
      metabolic pathways in Arabidopsis. Using CressExpress together with desktop
      visualization and analysis tools, one can easily identify clusters of genes that
      are co-expressed with one or more genes of interest, making it possible to
      identify new players in metabolic pathways that are regulated at the level of
      mRNA abundance.

PMID- 19588110
TI  - Integration of metabolic reactions and gene regulation.
AB  - Metabolic reactions and gene regulation are two primary processes of cells. In
      response to environmental changes cells often adjust the regulatory programs and
      shift the metabolic states. An integrative investigation and modeling of these
      two processes would improve our understanding of the cellular systems and may
      generate substantial impacts in medicine, agriculture, environmental protection,
      and energy. We review the studies of the various aspects of the crosstalk between
      metabolic reactions and gene regulation, including models, empirical evidence,
      and available databases.

PMID- 19588111
TI  - Applying word-based algorithms: the IMEter.
AB  - Important patterns can be found in strings of characters such as nucleotides in a
      DNA sequence by examining the frequency of occurrence of specific character
      combinations or words. The abundance of words can reveal the presence of
      underlying trends governing the order of characters, even if the biological
      reasons for those trends remain mysterious. As an example of one way in which
      word frequencies have provided insight, we describe the IMEter, a word-based
      algorithm for analyzing introns and their effect on gene expression. The IMEter
      demonstrates that introns located near the beginning of genes are compositionally
      distinct from later introns and that these differences are closely related to the
      ability of some introns to increase gene expression. This word-based approach has
      proven more successful than deletion analysis at identifying the sequences
      responsible for elevating expression because they are dispersed throughout
      stimulatory introns.

PMID- 19588112
TI  - Live-imaging and image processing of shoot apical meristems of Arabidopsis
      thaliana.
AB  - The shoot apical meristem (SAM) of higher plants represents a dynamic network of
      different cell types which exhibit distinct patterns of gene expression and
      cellular behaviors. The regulation of distinct patterns of gene expression and
      cellular behaviors is mediated by cell-cell communication networks. Live-imaging
      of spatiotemporal dynamics of cell-cell communication networks, gene expression
      patterns, and cellular behaviors is critical to deduce principles that underlie
      SAM growth and maintenance. In this chapter, we describe live-imaging methods,
      fluorescent reagents, and image processing protocols that have been developed to
      visualize the regulatory dynamics of SAM growth in Arabidopsis thaliana.

PMID- 19588113
TI  - Computer vision as a tool to study plant development.
AB  - Morphological phenotypes due to mutations frequently provide key information
      about the biological function of the affected genes. This has long been true of
      the plant Arabidopsis thaliana, though phenotypes are known for only a minority
      of this model organism's approximately 25,000 genes. One common explanation for
      lack of phenotype in a given mutant is that a genetic redundancy masks the effect
      of the missing gene. Another possibility is that a phenotype escaped detection or
      manifests itself only in a certain unexamined condition. Addressing this
      potentially nettlesome alternative requires the development of more sophisticated
      tools for studying morphological development. Computer vision is a technical
      field that holds much promise in this regard. This chapter explains in general
      terms how computer algorithms can extract quantitative information from images of
      plant structures undergoing development. Automation is a central feature of a
      successful computer vision application as it enables more conditions and more
      dependencies to be characterized. This in turn expands the concept of phenotype
      into a point set in multidimensional condition space. New ways of measuring and
      thinking about phenotypes, and therefore the functions of genes, are expected to
      result from expanding the role of computer vision in plant biology.

PMID- 19588114
TI  - Metabolomics of plant volatiles.
AB  - Plants communicate with their surrounding ecosystems using a diverse array of
      volatile metabolites that are indicative of the physiological status of the
      emitter. A variety of systems have been adapted to capture, analyze, identify,
      and quantify airborne metabolites released by plants. Metabolomic experiments
      typically involve four steps: sample collection, preparation, product separation,
      and data analysis. To date, two different types of headspace sampling, static and
      dynamic, are widely used for volatile metabolome investigation. For static
      headspace analysis, solid-phase microextraction (SPME) is used to sample
      volatiles while push and pull as well as closed-loop stripping methods are used
      for dynamic headspace sampling. After collection, volatile blends are most
      efficiently and routinely separated prior to analysis using gas chromatography
      (GC). Sample preparation is simplified because derivatization is not needed with
      volatile metabolites. GC coupled to detection by electron impact mass
      spectrometry (EI-MS) provides high chromatographic resolution, sensitivity,
      compound-specific detection, quantitation, and the potential to identify unknowns
      by characteristic and reproducible fragmentation spectra in addition to retention
      time. A variety of resources can be used to identify unknown compounds in a given
      volatile sample including >600,000 compounds with known mass spectra catalogued
      in searchable mass spectral libraries.

PMID- 19588115
TI  - Chemical genomics approaches in plant biology.
AB  - Chemical genomics (i.e., genomics-scale chemical genetics) approaches are based
      on the ability of low-molecular-mass molecules to modify biological processes.
      Such molecules are used to affect the activity of a protein or a pathway in a
      manner that is tunable and reversible. A major advantage of this approach
      compared to classical plant genetics is the fact that chemical genomics can
      address loss-of-function lethality and redundancy. Bioactive chemicals resulting
      from forward or reverse chemical screens can be useful in understanding and
      dissecting complex biological processes due to the essentially limitless
      variation in structure and activities inherent in chemical space. An important
      aspect of utilizing small molecules effectively is to characterize bioactive
      chemicals in detail including an understanding of structure activity
      relationships (SARs) and the identification of active and inactive analogs.
      Bioactive chemicals can be useful as reagents to probe biological pathways
      directly. However, the identification of cognate targets and their pathways is
      also informative and can be achieved by screens for genetic resistance or
      hypersensitivity in Arabidopsis thaliana or other organisms in which the results
      can be translated to plants. Here, we describe approaches to screen for bioactive
      chemicals that affect biological processes in Arabidopsis. We will also discuss
      considerations for the characterization of bioactive compounds and genetic
      screens for target identification. This should provide those who are considering
      this approach some practical knowledge of how to design and establish a chemical
      genomics screen.

PMID- 19588117
TI  - Democratization and integration of genomic profiling tools.
AB  - Systems biology is a comprehensive means of creating a complete understanding of
      how all components of an organism work together to maintain and procreate life.
      By quantitatively profiling one at a time, the effect of thousands and millions
      of genetic and environmental perturbations on the cell, systems biologists are
      attempting to recreate and measure the effect of the many different states that
      have been explored during the 3 billion years in which life has evolved. A key
      aspect of this work is the development of innovative new approaches to quantify
      changes in the transcriptome, proteome, and metabolome. In this chapter we
      provide a review and evaluation of several genomic profiling techniques used in
      plant systems biology as well as make recommendations for future progress in
      their use and integration.

PMID- 19588118
TI  - The potato R locus codes for dihydroflavonol 4-reductase.
AB  - The potato R locus is required for the production of red pelargonidin-based
      anthocyanin pigments in potato (Solanum tuberosum L.). Red color also requires
      tissue-specific regulatory genes, such as D (for expression in tuber skin) and F
      (expression in flowers). A related locus, P, is required for production of
      blue/purple anthocyanins; P is epistatic to R. We have previously reported that
      the dihydroflavonol 4-reductase gene (dfr) co-segregates with R. To test directly
      whether R corresponds to dfr, we placed the allele of dfr associated with red
      color under the control of the CaMV 35S promoter and introduced it into the
      potato cultivar Prince Hairy (genotype dddd rrrr P-), which has white tubers and
      pale blue flowers. Transgenic Prince Hairy tubers remained white, but flower
      color changed to purple. Three independent transgenic lines, as well as a vector
      transformed line, were then crossed with the red-skinned variety Chieftain
      (genotype D-R-pppp), to establish populations that segregated for D, R, P, and
      the dfr transgene or empty vector. Markers were used to genotype progeny at D and
      R. Progeny carrying the empty vector in the genetic background D-rrrr produced
      white or purple tubers, while progeny with the same genotype and the dfr
      transgene produced red or purple tubers. HPLC and LC-MS/MS analyses of
      anthocyanins present in Chieftain and in a red-skinned progeny clone with the dfr
      transgene in a D-rrrr background revealed no qualitative differences. Thus, dfr
      can fully complement R, both in terms of tuber color and anthocyanin composition.

PMID- 19588116
TI  - Comparison of quantitative metabolite imaging tools and carbon-13 techniques for
      fluxomics.
AB  - The recent development of analytic technologies allows fast analysis of
      metabolism in real time. Fluxomics aims to define the genes involved in
      regulation of flux through a metabolic or signaling pathway. Flux through a
      metabolic or signaling pathway is determined by the activity of its individual
      components; regulation can occur at many levels, including transcriptional,
      posttranslational, and allosteric levels. Currently two technologies are used to
      monitor fluxes. The first is pulse labeling of the organism with a tracer such as
      C13, followed by mass spectrometric analysis of the partitioning of label into
      different compounds. The second approach is based on the use of flux sensors,
      proteins that respond with a conformational change to ligand binding.
      Fluorescence resonance energy transfer (FRET) detects the conformational change
      and serves as a proxy for ligand concentration. Both methods provide high time
      resolution. In contrast to mass spectrometry assays, FRET nanosensors monitor
      only a single compound, but the advantage of FRET nanosensors is that they yield
      data with cellular and subcellular resolution.

PMID- 19588119
TI  - Fine mapping and candidate gene analysis of spd6, responsible for small panicle
      and dwarfness in wild rice (Oryza rufipogon Griff.).
AB  - Identification of genes in rice that affect production and quality is necessary
      for improving the critical global food source. CSSL58, a chromosome segment
      substitution line (CSSL) containing a chromosome segment of Oryza rufipogon in
      the genetic background of the indica cultivar Teqing showed significantly smaller
      panicles, fewer grains per panicle, smaller grains and dwarfness compared with
      the recurrent parent Teqing. Genetic analysis of the BC(4)F(1) and BC(4)F(2)
      generations, derived from a cross between CSSL58 and Teqing, showed that these
      traits are controlled by the recessive gene spd6, which mapped to the short arm
      of chromosome 6. Fine mapping and high-resolution linkage analysis using 24,120
      BC(4)F(3) plants and markers flanking spd6 were carried out, and the gene was
      localized to a 22.4 kb region that contains four annotated genes according to the
      genome sequence of japonica Nipponbare. Phenotypic evaluation of the nearly
      isogenic line NIL(spd6) revealed that spd6 from wild rice has pleiotropic effects
      on panicle number per plant, grain size, grain weight, grain number per panicle
      and plant height, suggesting that this gene might play an important role in the
      domestication of rice. The discovery of spd6 may ultimately be useful for the
      design and breeding of crops with high grain yield and quality.

PMID- 19588120
TI  - Insulin glargine use and short-term incidence of malignancies-a population-based
      follow-up study in Sweden.
AB  - AIMS/HYPOTHESIS: In the light of a report suggesting that insulin glargine may
      increase cancer occurrence, the EASD asked us to perform this study. METHODS: We
      followed 114,841 individuals who had a prescription dispensed for insulin between
      1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted
      the occurrence of malignancies. Seven different nationwide registers were used to
      obtain information on insulin exposure, outcome and possible confounders; these
      were linked using the unique personal identity number assigned to every Swedish
      resident. RESULTS: After adjustment for age and, when appropriate, sex, users of
      insulin glargine alone (no other types of insulin), compared with users of types
      of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31-3.03) for
      breast cancer, 0.93 (95% CI 0.61-1.40) for gastrointestinal cancer, 1.27 (95% CI
      0.89-1.82) for prostate cancer and 1.07 (95% CI 0.91-1.27) for any type of
      malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at
      birth of first child, cardiovascular disease and oestrogen use gave an RR for
      breast cancer of 1.97 (95% CI 1.29-3.00). The 95% CIs crossed 1.0 for the RR
      calculated in all analyses of users of insulin glargine in combination with other
      types of insulin. CONCLUSIONS/INTERPRETATION: In Sweden, during 2006 and 2007,
      women using insulin glargine alone (no other types of insulin) had an increased
      incidence rate of breast cancer as compared with women using types of insulin
      other than insulin glargine. This result may be due to a random fluctuation; the
      possibilities for examining validity are limited, and no statistically
      significant results were obtained for any other individual cancer site or for the
      outcome 'all malignancies'. No definitive conclusions regarding a possible causal
      relationship between insulin glargine use and the occurrence of malignancies can
      be drawn from the results of this study.

PMID- 19588121
TI  - Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle
      protein anabolism in older adults: evidence of a true age-related insulin
      resistance of muscle protein metabolism.
AB  - AIMS/HYPOTHESIS: The physiological increase in muscle protein anabolism induced
      by insulin is blunted in healthy, glucose-tolerant older adults. We hypothesised
      that the age-related defect in muscle protein anabolism is a true insulin
      resistance state and can be overridden by supraphysiological hyperinsulinaemia.
      METHODS: We used dye dilution, stable isotopic and immunoblotting techniques to
      measure leg blood flow, muscle protein synthesis, protein kinase B/mammalian
      target of rapamycin (Akt/mTOR) signalling, and amino acid kinetics in 14 healthy,
      glucose-tolerant older volunteers at baseline, and during an insulin infusion at
      postprandial (PD, 0.15 mU min(-1) 100 ml(-1)) or supraphysiologically high (HD,
      0.30 mU min(-1) 100 ml(-1)) doses. RESULTS: Leg blood flow, muscle protein
      synthesis, and Akt/mTOR signalling were not different at baseline. During
      hyperinsulinaemia, leg blood flow (p < 0.01) and muscle protein synthesis
      increased in the HD group only (PD [%/h]: from 0.063 +/- 0.006 to 0.060 +/-
      0.005; HD [%/h]: from 0.061 +/- 0.007 to 0.098 +/- 0.007; p < 0.01). Muscle Akt
      phosphorylation increased in both groups, but the increase tended to be greater
      in the HD group (p = 0.07). The level of p70 ribosomal S6 kinase 1 (S6K1)
      phosphorylation increased in the HD group only (p < 0.05). Net amino acid balance
      across the leg improved in both groups, but a net anabolic effect was observed
      only in the HD group (p < 0.05). CONCLUSIONS/INTERPRETATION: We conclude that
      supraphysiological hyperinsulinaemia is necessary to stimulate muscle protein
      synthesis and anabolic signalling in healthy older individuals, suggesting the
      existence of a true age-related insulin resistance of muscle protein metabolism.

PMID- 19588123
TI  - Ethanol and liver: recent advances in the mechanisms of ethanol-induced
      hepatosteatosis.
AB  - Ethanol-induced fatty liver is a worldwide health problem without effective
      therapeutic methods. The underlying mechanisms are extremely complex and not
      fully understood. The hepatosteatosis caused by ethanol can be attributed to many
      factors, including the changes of the redox condition, transportation impairment
      of the synthesized lipid, inhibition of fatty acid oxidation, and the enhancement
      of the lipogenesis. Recent studies focus on the reduced oxidation of fatty acid
      and the enhancement of the do novo lipogenesis, and several factors are
      sequentially revealed. Two important nuclear transcription factors, peroxisome
      proliferators-activated receptor alpha (PPARalpha) and sterol regulatory element
      binding protein-1 (SREBP-1), and the lipid metabolism-associated enzymes
      regulated by the two molecules, are shown to be involved in ethanol-induced
      steatosis. The AMP-dependent protein kinase, adiponectin, and tumor necrosis
      factor alpha (TNF-alpha) may mediate the modulation of ethanol on PPARalpha and
      SREBP-1. In addition, a number of studies demonstrate that plasminogen activator
      inhibitor-1 (PAI-1) is also involved in ethanol- induced fatty liver, and its
      effects may be associated with the TNF-alpha production. Furthermore, the role of
      CYP2E1 has also been investigated. Some studies showed that CYP2E1 played a
      critical role in the development of alcoholic fatty liver, which was denied by
      other reports. As such, the exact role of CYP2E1 needs to be further studied.

PMID- 19588122
TI  - Plasma tryptophan and tyrosine levels are independent risk factors for delirium
      in critically ill patients.
AB  - AIM: The pathophysiology of delirium remains elusive though neurotransmitters and
      their precursor large neutral amino acids (LNAAs) may play a role. This pilot
      study investigated whether alterations of tryptophan (Trp), phenylalanine (Phe),
      and tyrosine (Tyr) plasma levels were associated with a higher risk of
      transitioning to delirium in critically ill patients. METHODS: Plasma LNAA
      concentrations were determined on days 1 and 3 in mechanically ventilated (MV)
      patients from the MENDS randomized controlled trial (dexmedetomidine vs.
      lorazepam sedation). Three independent variables were calculated by dividing
      plasma concentrations of Trp, Phe, and Tyr by the sum of all other LNAA
      concentrations. Delirium was assessed daily using the confusion assessment method
      for the intensive care unit (CAM-ICU). Markov regression models were used to
      analyze independent associations between plasma LNAA ratios and transition to
      delirium after adjusting for covariates. RESULTS: The 97 patients included in the
      analysis had a high severity of illness (median APACHE II, 28; IQR, 24-32). After
      adjusting for confounders, only high or very low tryptophan/LNAA ratios (p =
      0.0003), and tyrosine/LNAA ratios (p = 0.02) were associated with increased risk
      of transitioning to delirium, while phenylalanine levels were not (p = 0.27).
      Older age, higher APACHE II scores and increasing fentanyl exposure were also
      associated with higher probabilities of transitioning to delirium. CONCLUSIONS:
      In this pilot study, plasma tryptophan/LNAA and tyrosine/LNAA ratios were
      associated with transition to delirium in MV patients, suggesting that
      alterations of amino acids may be important in the pathogenesis of ICU delirium.
      Future studies evaluating the role of amino acid precursors of neurotransmitters
      are warranted in critically ill patients.

PMID- 19588126
TI  - Difficulties in fumonisin determination: the issue of hidden fumonisins.
AB  - In this paper, the results obtained by five independent methods for the
      quantification of fumonisins B(1), B(2), and B(3) in raw maize are reported. Five
      naturally contaminated maize samples and a reference material were analyzed in
      three different laboratories. Although each method was validated and common
      calibrants were used, a poor agreement about fumonisin contamination levels was
      obtained. In order to investigate the interactions among analyte and matrix
      leading to this lack of consistency, the occurrence of fumonisin derivatives was
      checked. Significant amounts of hidden fumonisins were detected for all the
      considered samples. Furthermore, the application of an in vitro digestion
      protocol to raw maize allowed for a higher recovery of native fumonisins,
      suggesting that the interaction occurring among analytes and matrix
      macromolecules is associative rather than covalent. Depending on the analytical
      method as well as the maize sample, only 37-68% of the total fumonisin
      concentrations were found to be extractable from the samples. These results are
      particularly impressive and significant in the case of the certified reference
      material, underlying the actual difficulties in ascertaining the trueness of a
      method for fumonisin determination, opening thus an important issue for risk
      assessment.

PMID- 19588125
TI  - The involvement of type IV phosphodiesterases in cocaine-induced sensitization
      and subsequent pERK expression in the mouse nucleus accumbens.
AB  - RATIONALE: Cocaine exposure produces sensitization that is partly mediated by
      cyclic adenosine monophosphate (cAMP) pathways within the nucleus accumbens
      (NAc). Type IV phosphodiesterases (PDE4s) break down cAMP and are required for
      cocaine-induced conditioned place preference. Whether PDE4 disruption attenuates
      induction of behavioral sensitization to cocaine and subsequent NAc expression of
      phosphorylated extracellular signal-regulated kinase (ERK), which is involved in
      cocaine-induced sensitization, is unknown. OBJECTIVES: The objective of this
      study was to determine whether inhibition of PDE4s prevents cocaine-induced
      locomotor sensitization and if reduced behavioral sensitization is accompanied by
      decreased expression of phosphorylated ERK (pERK) within the NAc. METHODS: Mice
      were administered the PDE4 inhibitor, rolipram, or vehicle before or after five
      daily injections of cocaine or saline, and activity was monitored on days 1 and
      5. After nine drug-free days, locomotor sensitization was tested. Some subjects
      were sacrificed following testing for behavioral sensitization to measure pERK
      expression in the NAc. RESULTS: PDE4 inhibition, during the induction of
      sensitization, reduced behavioral sensitization only if rolipram (1.0 mg/kg) was
      administered before cocaine. Re-exposure to the cocaine-paired environment
      following a 9-day drug-free period enhanced pERK expression in the NAc core and
      shell. Rolipram did not alter pERK induction despite blocking behavioral
      sensitization. CONCLUSIONS: Rolipram given during, but not following, cocaine
      treatment prevents development of locomotor sensitization to cocaine but does not
      affect subsequent pERK activation induced by exposure to a cocaine-paired context
      or following a cocaine challenge. Although PDE4 inhibition during the induction
      of sensitization blocks the locomotor component of sensitization, other long-term
      changes induced by repeated cocaine treatment remain.

PMID- 19588128
TI  - Real-time trace detection of security-relevant compounds in complex sample
      matrices by thermal desorption-single photon ionization-ion trap mass
      spectrometry (TD-SPI-ITMS).
AB  - For the detection of security-relevant substances at low concentrations in
      complex matrices, coupling of thermal desorption-single photon ionization-ion
      trap mass spectrometry (TD-SPI-ITMS) was successfully tested. The main advantage
      of taking solid samples with a wipe pad followed by thermal desorption is the low
      detection limit by enhanced vapor pressure. Single photon ionization is a soft
      ionization technique which reduces the target ion fragmentation and shields bulk
      components with high ionization energies (IE) like nitrogen yielding to clearly
      arranged mass spectra with significant high mass peaks. To obtain low false
      positive and false-negative rates, especially necessary for security-relevant
      substances, the ion trap mass spectrometer allows identification of signals with
      MS/MS studies. In this concept, the soft ionization technique fits well with the
      MS/MS studies, as peaks with high masses are generated yielding significant MS/MS
      fragments. For the ionization, photon energies between about 8 eV (155 nm) and 12
      eV (103 nm) were generated with electron-beam-pumped rare gas excimer lamps
      (EBEL). Depending on the rare gas used, light with different photon energy is
      generated, adapted to the substances of interest. So, even most narcotics, having
      relatively low IEs, can be ionized with 8.4 eV photons without massive
      fragmentation. For most explosives, photons with higher energy must be used as
      their IEs are higher. In this work, a mobile setup with a commercial ion trap
      mass spectrometer has been developed and tested. Even a first real-scenario
      measurement campaign was accomplished successfully proving the field-suitability
      of the system.

PMID- 19588124
TI  - Intracerebroventricular administration of cannabinoid CB1 receptor antagonists
      AM251 and AM4113 fails to alter food-reinforced behavior in rats.
AB  - RATIONALE: Drugs that interfere with cannabinoid CB1 transmission suppress food
      motivated behaviors and may be useful as appetite suppressants, but there is
      uncertainty about the locus of action for the feeding-suppression effects of
      these drugs. OBJECTIVE: The present work was conducted to determine if two drugs
      that interfere with cannabinoid receptor transmission, AM251 and AM4113, have
      effects on food-reinforced behavior after administration into the lateral
      ventricle (intracerebroventricular (ICV)). RESULTS: Although systemic
      administration of both drugs can suppress food-reinforced behavior, neither AM251
      (40, 80, and 160 microg) nor AM4113 (60, 120, and 240 microg) administered at
      various times prior to testing produced any suppression of food-reinforced
      operant responding on a fixed-ratio 5 schedule. Because the modulation of
      locomotion by drugs that act on CB1 receptors is hypothesized to be a forebrain
      effect, these drugs also were assessed for their ability to reverse the locomotor
      suppression produced by the CB1 agonist AM411. ICV administration of either AM251
      or AM4113 reversed the locomotor suppression induced by the CB1 agonist AM411 in
      the same dose range that failed to produce any effects on feeding. CONCLUSIONS:
      This indicates that both AM4113 and AM251, when administered ICV, can interact
      with forebrain CB1 receptors and are efficacious on forebrain-mediated functions
      unrelated to feeding. These results suggest that CB1 neutral antagonists or
      inverse agonists may not be affecting food-reinforced behavior via interactions
      with forebrain CB1 receptors located in nucleus accumbens or hypothalamus and
      that lower brainstem or peripheral receptors may be involved.

PMID- 19588129
TI  - Potential-modulated fluorescence spectroscopy of the membrane potential-sensitive
      dye di-4-ANEPPS at the 1,2-dichloroethane/water interface.
AB  - The spectrofluorometric behavior of a membrane potential-sensitive dye, 1-(3
      sulfonatopropyl)-4-[beta-{2-(di-N-butylamino)-6-naphthyl}vinyl]pyridinium betaine
      (di-4-ANEPPS), at the polarized 1,2-dichloroethane/water interface was studied by
      means of potential-modulated fluorescence (PMF) spectroscopy. The results,
      combined with those from cyclic and alternating current voltammetry, clearly
      suggested that the dye adsorbed at the interface underwent a reorientation with
      increasing the interfacial potential, giving a well-developed PMF response as
      well as a voltammetric response. In addition to the PMF response, another PMF
      response was observed by addition of dilauroyl phosphatidylcholine (DLPC). This
      additional response was well explained in terms of a reorientation of di-4-ANEPPS
      at the interface, which would be induced by the potential-dependent desorption of
      DLPC from the interface. Thus, the present study supported the
      reorientation/solvatochromic mechanism for the membrane potential-sensitive dye
      rather than the electrochromic mechanism.

PMID- 19588131
TI  - Hepatic failure in a rapidly involuting congenital hemangioma of the liver:
      failure of embolotherapy.
AB  - We report the clinical course, imaging findings, and management of a rare case of
      rapidly involuting congenital hemangioma of the liver in a newborn girl. The baby
      presented with severe progressive hepatic dysfunction and cardiomegaly.
      Multimodality imaging demonstrated a large hypervascular solitary hepatic mass
      with marked transhepatic shunting, consistent with rapidly involuting congenital
      hemangioma. Because medical therapy failed, transarterial and transvenous
      embolization was performed with the main intention to improve the hepatic
      perfusion and function. Unfortunately, despite improvement in the cardiac
      overload, liver function continued to deteriorate. The baby eventually underwent
      successful liver transplantation.

PMID- 19588130
TI  - MRI diagnosis and preoperative evaluation for pure epidural cavernous
      hemangiomas.
AB  - INTRODUCTION: The aims of the study were to summarize the characteristics of the
      spinal epidural cavernous hemangioma, especially for the MRI, and to improve the
      accurate rate of the preoperative diagnosis. METHODS: The clinical and medical
      imaging data of six patients with pure spinal epidural cavernous hemangioma
      proved by operation and pathology were analyzed retrospectively. RESULTS: The
      level was thoracic (n = 2), thoracolumbar (n = 1), lumbar (n = 1), and sacral (n
      = 2). The tumor showed lobulated contour, and the areas the tumors appeared were
      dorsal side of spinal cord (n = 2), ventral side (n = 1), and lateral side (n =
      3). In all six patients, the lesions were isointense to the spinal cord on T(1)
      weighted images and hyperintense on T(2)-weighted images and showed homogeneously
      strong enhancement on contrast-enhanced T(1)-weighted images. The characteristic
      MRI features were named as the "wafting-silk" sign. Widening of the
      intervertebral neural foramen (n = 4) and erosion of the adjacent bones (n = 3)
      can be observed. CONCLUSIONS: MRI of the epidural cavernous hemangioma showed the
      characteristic lobulated contour, which encircled the spinal cord. T(1)WI on the
      MRI presented as isointense and T(2)WI presented as hyperintense and a
      homogeneously strong enhancement, so we first proposed the sign of wafting silk.
      The widening of the intervertebral neural foramen and erosion of the adjacent
      bones can easily be observed. MR imaging has an important role in the detection
      and diagnosis of pure spinal epidural cavernous hemangioma.

PMID- 19588133
TI  - Symptomatic caval penetration by a Celect inferior vena cava filter.
AB  - We report a case of penetration of the inferior vena cava (IVC) by all four
      primary struts of a Celect caval filter in a 17-year-old girl with Klippel
      Trenaunay syndrome. The girl presented with acute lower abdominal and right leg
      pain 17 days after filter insertion. An abdominal radiograph demonstrated that
      the filter had moved caudally and that the primary struts had splayed
      considerably since insertion. Contrast-enhanced CT confirmed that all four
      primary struts had penetrated the IVC wall. There was a small amount of
      retroperitoneal hemorrhage. The surrounding vessels and viscera were intact. The
      filter was subsequently retrieved without complication.

PMID- 19588132
TI  - Optic neuropathy in a patient with pyruvate dehydrogenase deficiency.
AB  - Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial
      metabolism. The clinical manifestations range from severe neonatal lactic
      acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical
      sequela and the imaging findings of optic neuropathy in these patients have not
      previously been described. We present a patient with PDH deficiency with
      bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy
      and chiasmopathy.

PMID- 19588134
TI  - Denervation-related fatty muscle infiltration.

PMID- 19588135
TI  - Characterization and ligand specificity of sheep IgG2 receptor.
AB  - Neutrophils and macrophages in cattle express a novel class of immunoglobulin Fc
      receptor, specific for bovine IgG2, termed boFcgamma2R. In cows, the ability of
      neutrophils to kill immunoglobulin-opsonized microorganisms appears to depend
      largely on this subclass. Although related to other mammalian FcgammaRs,
      boFcgamma2R belongs to a novel gene family that includes the human killer Ig-like
      receptor and FcalphaRI (CD89) proteins. In this study, we describe the presence
      and characterization of this novel class of FcgammaR in sheep. The comparative
      analysis of this novel FcgammaR has allowed us to begin an exploration of some
      immunological characteristic of ruminants.

PMID- 19588136
TI  - A histopathological evaluation of a concave-shaped low-intensity band on T1
      weighted MR images in a subchondral insufficiency fracture of the femoral head.
AB  - A 73-year-old female suffered from right hip pain without any history of
      antecedent trauma. The initial radiograph showed a slight narrowing of the joint
      space in the right hip. The patient was treated by non-weight bearing for 5
      weeks. Radiographs obtained 3 months after the onset of pain showed the
      progression of both the joint-space narrowing and subchondral collapse at the
      superior portion. T1-weighted MR (magnetic resonance) images obtained 3 months
      after the onset revealed an irregular-shaped low-intensity area just beneath the
      articular cartilage as well as a low-intensity band, which was concave to the
      articular surface. A total hip replacement was performed. A histopathological
      examination revealed fracture callus and granulation tissue in the subchondral
      area. This subchondral fractured area was surrounded by vascular rich granulation
      tissue and fibrous tissue, which corresponded to the concave-shaped low-intensity
      band observed on the T1-weighted image.

PMID- 19588138
TI  - Abdominal pain in a patient with acute lymphoblastic leukaemia.

PMID- 19588137
TI  - Meniscal tears with displaced fragments: common patterns on magnetic resonance
      imaging.
AB  - OBJECTIVE: To identify the commonly occurring patterns of small displaced tears
      of the menisci of the knee on magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: A retrospective review of knee MRI scans over 16 months at two hospitals
      provided 70 studies with 73 displaced meniscal fragments for analysis. Fragment
      position was recorded. RESULTS: Two common positions were identified for medial
      fragments. For the medial meniscus, 93% of fragments were positioned medially or
      posterolaterally. The medially displaced fragments were positioned in either the
      superior or inferior recesses. Lateral meniscal fragments were more evenly
      dispersed. CONCLUSION: The pattern of small displaced tears of the medial
      meniscus is highly predictable. Awareness of the typical locations of these
      fragments should aid the reporter in identifying these lesions on MRI.

PMID- 19588139
TI  - Intestinal perforation associated with rituximab therapy for post-transplant
      lymphoproliferative disorder after liver transplantation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a serious complication
      after organ transplantation with a cumulative incidence of 1.1% at 18 months and
      4.7% at 15 years. It has been reported in patients with or without concomitant
      Epstein-Barr virus infection. Therapy ranges from a reduction of
      immunosuppression to administration of conventional cytotoxic chemotherapy.
      Rituximab, a recombinant chimeric anti-CD20 monoclonal antibody has been used for
      the treatment of PTLD with promising results and a reduction in treatment
      associated mortality. However, the use of rituximab has been associated with
      spontaneous gastrointestinal perforation. We describe a case of recurrent
      intestinal perforations after a single dose of rituximab.

PMID- 19588140
TI  - Ambulatory administration of 5-day infusion ifosfamide+mesna: a pilot study in
      sarcoma patients.
AB  - PURPOSE: Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue
      sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of
      ifosfamide should be repeated doses over several days. With the development of 5
      day infusion devices, we developed and evaluated a 5-day infusion regimen of
      ifosfamide in sarcoma patients in the outpatient setting. METHODS: Sarcoma
      patients requiring chemotherapy after at least one doxorubicin-based line were
      enrolled in this study. Ifosfamide+mesna was administered as 1:1 concentration
      for a total of 6 g/m2 of each over 5 days (i.e. 1.2 g/m2 per day as continuous
      infusion) every 3 weeks. Patients were treated until progression or limiting
      toxicity, and salvage surgery was attempted when possible. An economic study was
      run comparing ifosfamide plus mesna as a 5-day infusion regimen and conventional
      Ifosfamide regimen. RESULTS: Thirteen sarcoma patients were evaluable. The median
      number of cycles per patient was 6 (range, 1-8), for a total of 69 cycles. No
      acute encephalopathy or aggravation of renal function was noted. Acute grade 3
      and 4 haematological toxicities were observed in 11.6 and 1.4% of patients,
      respectively without febrile neutropenia. Median time to progression survival and
      overall survival were 8.7 and 21.5 months, respectively. Total cost per cycle for
      a 2-m2 patient body surface area was ambulatory infusion=1,891 euros and
      conventional ifosfamide=6,256 euros. CONCLUSION: The combination of ifosfamide
      and mesna as a continuous infusion over 5 days is feasible and well tolerated in
      the outpatient setting using infusion device. Its very favourable cost
      effectiveness invites to further develop this approach.

PMID- 19588142
TI  - Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis:
      a meta-analysis.
AB  - The aim of this study was to determine whether the rs7574865 polymorphism of
      STAT4 (signal transducers and activators of transcription 4) confers
      susceptibility to rheumatoid arthritis (RA) in populations with different
      ethnicities. A meta-analysis was conducted on the T allele of the STAT4 rs7574865
      polymorphism in 15 studies containing 16,088 RA patients and 16,509 normal
      control subjects. Meta-analysis revealed an association between RA and the STAT4
      rs7574865 T allele in all subjects (OR = 1.271, 95% CI = 1.197-1.350, P < 0.001).
      Furthermore, the STAT4 rs7574865 T allele was found to be significantly
      associated with RA in Europeans and Asians (OR = 1.300, 95% CI = 1.195-1.414, P <
      0.001; OR = 1.216, 95% CI = 1.135-1.303, P < 0.001). Stratification of RA
      patients according to the presence of anti-CCP antibody revealed a statistically
      significant association between the T allele and RA in both anti-CCP-positive and
      -negative RA patients versus controls. Europeans had the lowest (21.4%) and
      Asians had the highest (32.0%) prevalence of the T allele among the populations
      studied. In conclusion, this meta-analysis confirms that the STAT4 rs7574865
      polymorphism is associated with RA susceptibility in different ethnic groups, and
      that its prevalence is ethnicity dependent.

PMID- 19588141
TI  - Effect of balneotherapy on temporospatial gait characteristics of patients with
      osteoarthritis of the knee.
AB  - Effects of balneotherapy on gait properties of patients with osteoarthritis of
      the knee were investigated prospectively. A total of 30 patients with knee
      osteoarthritis received balneotherapy consisting of two daily thermomineral water
      baths for 2 weeks. Patients were evaluated using gait analysis and clinical
      scores, both within 2 weeks, before and after spa treatment. Patients were
      walking faster in their control analyses (0.81 +/- 0.21 to 0.89 +/- 0.19 m/s; P =
      0.017), with a shorter mean stance time (63.0 +/- 3.3 to 61.8 +/- 2.5% stride; P
      = 0.007), an increased cadence (96 +/- 13.1 to 100 +/- 11.9 steps/min; P = 0.094)
      and stride length (996 +/- 174 to 1,058 +/- 142 mm; P = 0.017). Balneotherapy
      also resulted in a significant decrease in Lequesne knee osteoarthritis index
      (12.1 +/- 3.7 to 10.0 +/- 3.3 points; P = 0.003), VAS for pain (58 +/- 25 to 33
      +/- 15; P = 0.0001), VAS for patients' (56 +/- 24 to 29 +/- 19; P < 0.001) and
      investigator's global assessment (55 +/- 20 to 26 +/- 15; P < 0.0001) and WOMAC
      score (2.1 +/- 0.7 to 1.6 +/- 0.8; P = 0.0004). Balneotherapy has positive
      effects on gait properties and clinical health quality parameters of patients
      with knee osteoarthritis in short-term evaluations.

PMID- 19588143
TI  - Erdheim-Chester disease: a case report with pulmonary, kidney involvement and
      bone lesions.
AB  - We report the case of a 42-year-old woman who was admitted in 2002 for
      exploration of diffuse bone pain. She had medical history of pulmonary
      tuberculosis. Her current symptoms had started 9 months earlier and consisted of
      bone pain, affecting the legs. She had asthenia and weight loss. At admission,
      physical examination showed bilateral and symmetrical long bone pain, especially
      the knees and the ankles. Physical exam was normal elsewhere. Laboratory tests
      showed inflammation, with an erythrocyte sedimentation rate of 90 mm/h and C
      reactive protein 8 mg/l. Protein electrophoresis, red and white blood cell count,
      renal, and liver function tests were normal. Serum calcium, phosphorus, and
      urinary calcium were normal. Radiographs showed multiple mixed bone lesions with
      sclerotic and lytic areas of the femora, tibiae, humerus. Chest radiographs and
      thoracic computed tomography (CT) scan showed pulmonary fibrosis. Biopsy of the
      tibial area displayed foamy lipid-laden histiocytes, confirming the diagnosis of
      Erdheim-Chester disease. Patient was treated with prednisolone plus
      cyclophosphamide. Her clinical condition improved remarkably during 4 years, but
      she developed acute renal failure leading to death.

PMID- 19588144
TI  - FDG-PET/CT in large-vessel vasculitis: its diagnostic and follow-up role.
AB  - Vasculitis is a disorder characterized by inflammation of blood vessels. Its
      clinical manifestations are diverse and depend on the size of the involved
      vessels and the organs affected by ischemia. In some cases the disease is
      manifested only with symptoms and signs of systemic inflammation (e.g. fever,
      night sweats, fatigue). Results of laboratory tests usually indicate only the
      inflammatory process. It is known that radiolabeled glucose analogue 18F-fluoro
      deoxyglucose ([18F] FDG) used in positron emission tomography (PET) accumulates
      in both malignant and inflammatory tissue (Zhuang et al. in Radiol Clin North Am
      43:121-134, 2005). We report a case of a patient with FDG-PET/CT findings of
      large-vessel vasculitis with follow-up results that convinced us to change the
      treatment.

PMID- 19588145
TI  - Arterial spin labelling at 3-T MR imaging for detection of  individuals with
      Alzheimer's disease.
AB  - The purpose of this study was to determine whether arterial spin labelling (ASL)
      at 3-T MR imaging can be used to discriminate individuals with Alzheimer's
      disease (AD) from cognitively normal subjects. Twenty AD patients and 23
      cognitively normal control subjects were studied using ASL on a 3-T MR imager.
      Absolute regional cerebral blood flow (rCBF) maps were calculated. In addition,
      normalized rCBF maps were obtained using CBF in the sensorimotor cortex for
      normalization. A voxel-wise comparison of these rCBF maps between the AD and
      control groups was performed using the two-sample t test. Individuals with AD
      were discriminated from control subjects based on mean rCBF values within a
      region-of-interest defined by the t test, and the discriminating performance was
      evaluated by the receiver operating characteristic (ROC) analysis. Comparisons of
      both absolute and normalized rCBF maps revealed areas of significant
      hypoperfusion caused by the effects of AD in the bilateral precunei and posterior
      cingulate gyri. ROC analyses resulted in area under the curve (AUC) values of
      0.861 to 0.877 for absolute and 0.910 to 0.932 for normalized rCBF. Our results
      suggest that ASL at 3-T MR imaging can be used to help discriminate individuals
      with AD from normal subjects.

PMID- 19588146
TI  - Detection of intestinal bleeding with multi-detector row CT in an experimental
      setup. How many acquisitions are necessary?
AB  - The purpose of the study was to evaluate multi-detector computed tomography
      (MDCT) acquired in different acquisitions (unenhanced, and arterial and portal
      venous phase following intravenous contrast medium) for detection of intestinal
      bleeding using an experimental bowel model. The model consisted of an injector
      tube with a perforation placed in a 7-m-long small bowel of a pig. The bowel was
      filled with water/contrast medium solution of 30-40 HU and was incorporated in a
      phantom model. Intestinal bleeding in different locations and bleeding velocities
      varying from zero to 0.75 ml/min (0.05 ml/min increments) were simulated. Twenty
      six datasets in simulated unenhanced, arterial and portal venous contrast phase
      using increasing bleeding velocities and ten negative controls were measured
      using 64-row MDCT. Two radiologists blinded to the experimental settings
      evaluated the datasets in a random order. The likelihood of intestinal bleeding
      was assessed using a 5-point scale with subsequent ROC analysis. The overall
      sensitivity for detecting bleeding was 0.44 for an arterial acquisition alone,
      0.68 for a portal venous acquisition, 0.68 for the combination
      unenhanced/arterial, 0.72 for unenhanced/portal venous and 0.80 for
      arterial/portal. Bleeding velocities of above 0.25 ml/min were detected with a
      sensitivity of 0.59 for arterial, 0.88 for portal venous, 0.85 for
      unenhanced/arterial, 0.94 for unenhanced/portal venous and 0.97 for
      arterial/portal venous contrast phase protocols, respectively. The specificity
      was 1.00. MDCT provides the highest sensitivity and specificity in the detection
      of intestinal bleeding using arterial and portal venous acquisition in comparison
      to mono-phase protocols.

PMID- 19588147
TI  - The reliability of automatic measurement of left ventricular function with dual
      source computed tomography datasets.
AB  - The purpose of the study was to assess the reliability of (semi-) automatic left
      ventricular (LV) function measurements using three different software packages on
      the same dual-source computed tomography (DSCT) datasets and to compare agreement
      among the software packages. Forty consecutive patients, undergoing cardiac DSCT
      were included (31 men, mean age 58+/-14 years). LV function analysis was
      performed with all three software packages. ANOVA testing was used to determine
      the difference among the repeated measurements and the difference among the
      software packages. Bland-Altman plots were computed to describe the agreement
      among the software packages. No significant difference was found among the
      repeated measurements. In the comparison of the three software packages, a
      significant difference was observed when measurements were used with minimal user
      interaction. When end-diastolic and end-systolic phases were manually set, there
      was no overall significant difference, but in 12.5% of patients a large (>10%)
      difference in LVEF was found. All three software packages have good intraobserver
      variability, but the results of the three packages were significantly different.
      For clinical use, one should be aware of the clinical impact of possible
      segmentation flaws when (semi-)automatic LV function assessment is used.

PMID- 19588149
TI  - Gadofosveset-enhanced MR angiography of the pedal arteries in patients with
      diabetes mellitus and comparison with selective intraarterial DSA.
AB  - To compare gadofosveset-enhanced magnetic resonance angiography (MRA) of the
      pedal vasculature with selective intraarterial DSA. Eighteen patients with PAOD
      and type II diabetes were prospectively examined at 1.5 T. For contrast
      enhancement, 0.03 mmol/kg body weight gadofosveset was used. MR imaging consisted
      of dynamic and of high-resolution steady-state imaging. Selective digital
      subtraction angiography (DSA) was performed within 5 days and served as standard
      of reference. Image analysis was done by two observers. There were no differences
      between MRA and DSA regarding overall image quality. First-pass MRA detected
      significantly more patent vessel segments than did DSA (P<0.001, kappa=0.46).
      Interobserver agreement of MRA was very good with respect to the detection of
      patent vessel segments and the assessment of hemodynamically relevant stenoses
      (kappa=0.97 and 0.89, respectively). Steady-state imaging depicted significantly
      more patent metatarsal arteries than did dynamic imaging, and delineated
      inflammatory complications including osteomyelitis, soft-tissue abscesses, and
      fistulas related to the diabetic foot. Gadofosveset-enhanced MRA of the pedal
      vasculature proved to be superior to DSA. It offered a long imaging time window,
      and allowed for better depiction of the pedal outflow. Steady-state imaging
      delineated inflammatory complications associated with the diabetic foot.

PMID- 19588150
TI  - Foreign body extraction from soft tissue by using CT and fluoroscopic guidance: a
      new technique.
AB  - We report on a new minimally invasive technique for the retrieval of a surgical
      pin fragment after accidental migration into the soft tissue of the shoulder in
      two patients. The technique is performed under local anaesthesia and uses
      combined CT and fluoroscopic guidance. The materials used were simple, combining
      a bone biopsy needle and an endoscopy clamp. Pin displacement was confirmed under
      fluoroscopic guidance and the clamp was used to withdraw the pin to the cutaneous
      entry point under CT (step-by-step) guidance. The CT slices provide perfect
      visualisation of the vascular or nervous structures as well as perfect
      positioning of the extremity of the trocar relative to the material to be
      removed. This intervention avoids a second surgical intervention with a longer
      incision and avoided repeated general anaesthesia.

PMID- 19588148
TI  - Pretreatment evaluation of distant-site status in patients with nasopharyngeal
      carcinoma: accuracy of whole-body MRI at 3-Tesla and FDG-PET-CT.
AB  - We sought to prospectively evaluate the accuracy of 3.0-Tesla whole-body magnetic
      resonance imaging (WB-MRI) and integrated fluorodeoxyglucose (FDG) positron
      emission tomography (PET)/computed tomography (CT) (FDG-PETCT), and their
      combined interpretation for the assessment of distant-site status in 150 patients
      with untreated nasopharyngeal carcinoma (NPC). Eighteen (12%) patients were
      diagnosed as having distant malignancies (15 patients had distant metastases, and
      three distant synchronous tumours). On a patient-based analysis, WB-MRI and FDG
      PET-CT showed similar sensitivity (77.8% vs 72.2%, P>0.999), specificity (98.5%
      vs 97.7%, P > 0.999) and diagnostic capability (0.905 vs 0.878, P = 0.669).
      Combined interpretation of WB-MRI and FDGPET-CT showed no significant benefit
      over either technique alone. In conclusion, 3.0-Tesla WB-MRI is a feasible, non
      ionising technique that showed similar diagnostic capacity to FDG-PET-CT in
      assessing distant-site status in patients with untreated NPC and can be
      recommended as the first-line imaging technique for comprehensive evaluation of
      such patients.

PMID- 19588151
TI  - Clinical safety of cardiac magnetic resonance imaging at 3 T early after stent
      placement for acute myocardial infarction.
AB  - The purpose of this study was to prospectively evaluate the safety of cardiac
      magnetic resonance (CMR) imaging at 3 T performed early (less than 14 days) after
      bare metal or drug-eluting coronary stent implantation in patients with acute
      myocardial infarction (AMI). Seventy-two consecutive patients with AMI treated by
      percutaneous revascularisation with a stent underwent CMR examination with a
      median delay of 6 days. Patients were followed-up for major adverse cardiac
      events, during hospitalisation and at 6 months. After CMR imaging, no acute stent
      thrombosis, death or repeated AMI were recorded at 6-month follow-up. Two
      symptomatic in-stent restenoses and two silent in-stent restenoses were recorded,
      at a mean delay of 106 days. In our population, we found a target
      revascularisation rate of 5.6%. This is consistent with the 6-month event rates
      after coronary artery stent (CAS) placement for AMI, evaluated by several
      studies. This preliminary clinical study supports the safety of 3-T CMR imaging
      performed early after coronary stent placement.

PMID- 19588152
TI  - Detection and characteristics of microvascular obstruction in reperfused acute
      myocardial infarction using an optimized protocol for contrast-enhanced
      cardiovascular magnetic resonance imaging.
AB  - Several cardiovascular magnetic resonance imaging (CMR) techniques are used to
      detect microvascular obstruction (MVO) after acute myocardial infarction (AMI).
      To determine the prevalence of MVO and gain more insight into the dynamic changes
      in appearance of MVO, we studied 84 consecutive patients with a reperfused AMI on
      average 5 and 104 days after admission, using an optimised single breath-hold 3D
      inversion recovery gradient echo pulse sequence (IR-GRE) protocol. Early MVO (2
      min post-contrast) was detected in 53 patients (63%) and late MVO (10 min post
      contrast) in 45 patients (54%; p = 0.008). The extent of MVO decreased from early
      to late imaging (4.3+/-3.2% vs. 1.8+/-1.8%, p<0.001) and showed a heterogeneous
      pattern. At baseline, patients without MVO (early and late) had a higher left
      ventricular ejection fraction (LVEF) than patients with persistent late MVO (56+/
      7% vs. 48+/-7%, p<0.001) and LVEF was intermediate in patients with early MVO but
      late MVO disappearance (54+/-6%). During follow-up, LVEF improved in all three
      subgroups but remained intermediate in patients with late MVO disappearance. This
      optimised single breath-hold 3D IR-GRE technique for imaging MVO early and late
      after contrast administration is fast, accurate and allows detection of patients
      with intermediate remodelling at follow-up.

PMID- 19588154
TI  - Basic mechanisms of urgency: roles and benefits of pharmacotherapy.
AB  - INTRODUCTION: Since urgency is key to the overactive bladder syndrome, we have
      reviewed the mechanisms underlying how bladder filling and urgency are sensed,
      what causes urgency and how this relates to medical therapy. MATERIALS AND
      METHODS: Review of published literature. RESULTS: As urgency can only be assessed
      in cognitively intact humans, mechanistic studies of urgency often rely on proxy
      or surrogate parameters, such as detrusor overactivity, but these may not
      necessarily be reliable. There is an increasing evidence base to suggest that the
      sensation of 'urgency' differs from the normal physiological urge to void upon
      bladder filling. While the relative roles of alterations in afferent processes,
      central nervous processing, efferent mechanisms and in intrinsic bladder smooth
      muscle function remain unclear, and not necessarily mutually exclusive, several
      lines of evidence support an important role for the latter. CONCLUSIONS: A better
      understanding of urgency and its causes may help to develop more effective
      treatments for voiding dysfunction.

PMID- 19588153
TI  - Peritoneal cavity as bioreactor to grow autologous tubular urethral grafts in a
      rabbit model.
AB  - PURPOSE: To investigate whether peritoneal cavity could function as bioreactor to
      produce autologous tubular grafts for urethral reconstruction in male rabbits.
      METHODS: 8Fr silastic tubes were implanted into peritoneal cavities of nine male
      rabbits. By 2 weeks, tubes were harvested and the tubular tissue covering the
      tubes was everted. A pendulous urethral segment of 1.5 cm long was totally
      excised and urethroplasty was performed with the everted tubular tissue in an end
      to-end fashion. Another nine male rabbits underwent the same urethral resection
      and re-anastomosis as controls. Urethrography was performed at 1, 2 and 6 months
      postoperatively. Meanwhile, the neo-urethra were harvested and analyzed grossly
      and histologically. RESULTS: Histological analysis of the tubular tissue
      demonstrated transversely arranged myofibroblasts embedded in homogeneous
      collagen bundles and an outer layer of mesothelium. The tissue was easily everted
      and successfully transplanted as a urethral graft. Serial urethrography indicated
      no stricture or diverticula formation. While all animals of the control group
      developed stricture. Histological analysis of the neo-urethra demonstrated normal
      urethral architecture by 1 month, composed of multi-layers of urothelium
      surrounded by smooth muscle bundles, which became increasingly organized with
      time. By 6 months, the neo-urethra could be hardly distinguished from native
      urethra both grossly and histologically. CONCLUSIONS: These results show that the
      autologous tissue grown within the recipients' peritoneal cavity can be used
      successfully for tubularized urethral reconstruction in male rabbits.

PMID- 19588155
TI  - [Can HRT be a useful tool in differentiating lamellar macular holes from full
      thickness macular holes?].
AB  - BACKGROUND: The aim of this prospective study was to analyze the specificity and
      sensitivity of HRT 3 compared with spectral optical coherence tomography (SOCT)
      in differentiating full-thickness macular holes, lamellar macular holes, and
      macular pseudoholes. MATERIAL AND METHODS: In 128 patients with a diagnosis made
      by SOCT of full-thickness macular hole, lamellar macular hole, or macular
      pseudohole, 161 eyes were examined with the HRT 3 Retina Module, and the results
      were compared. RESULTS: Using SOCT, full-thickness macular holes were diagnosed
      in 80 eyes, pseudoholes in 15 eyes, and lamellar macular holes in 66 eyes. Using
      HRT, full-thickness macular holes were diagnosed in 81 eyes, and pseudoholes and
      lamellar macular holes (non-full-thickness macular holes) were diagnosed in 80
      eyes. In 160/161 cases, the diagnosis with HRT 3 was correct. Compared with SOCT,
      HRT 3 has a specificity of 98.7% and a sensitivity of 100% in differentiating
      full-thickness from non-full-thickness macular holes. CONCLUSION: The HRT 3
      macular module enables diagnosis of macular holes. Full-thickness macular holes
      could be differentiated from non-full-thickness macular holes; however, lamellar
      macular holes could not be differentiated from macular pseudoholes.

PMID- 19588156
TI  - [Comparison of parameters of time-resolved autofluorescence between healthy
      subjects and patients suffering from early AMD].
AB  - BACKGROUND: A fluorescence lifetime mapper (FLM) was tested for quantitative
      estimation of early alterations in age-related macular degeneration (AMD) which
      are assumed to be in cellular metabolism. METHOD: In FLM time-resolved
      autofluorescence of the fundus is excited by picosecond (ps) laser impulses at
      448 nm and detected in 2 spectral ranges (K1=490-560 nm and K2=560-700 nm) by
      time-correlated single photon counting. The time-dependent decrease in
      fluorescence intensity was approximated using 3 decay rates. The calculated
      lifetimes allow a comparison with endogenous fluorophores of cellular metabolism.
      RESULTS: Initially mean lifetimes were determined for 8 healthy subjects (K1:
      tau1=118 ps, tau2=584 ps, tau3=2826 ps, K2: tau1=104 ps, tau2=477 ps, tau3=1623
      ps). In 15 AMD patients (AREDS categories I and II) the lifetimes were longer
      (K1: tau1=166 ps, tau2=986 ps, tau3=3309 ps, K2: tau1=137 ps, tau2=583 ps,
      tau3=1924 ps). The best separation between healthy subjects and patients with
      early AMD was possible by parameters 1 and 2 in the short-wave channel.
      Fluorophore-specific alterations in the macula could be demonstrated in isolated
      cases with advanced AMD. CONCLUSION: Measurements in the 30 degrees fundus field
      demonstrated that specific alterations were already present even in early AMD and
      also outside the macula. These act in the neuronal retina, because parameter tau2
      is related to this layer. Increases in the lifetime of parameter tau2 in the
      short wave channel could at least partially be determined by an increase of
      protein bound NADH, the content of which increases with reduced cellular
      respiration.

PMID- 19588157
TI  - [Scanpath of experienced and inexperienced drivers in motor sports].
AB  - BACKGROUND: In analysing the information received by a driver of a motor vehicle,
      the visual system has an important position because the majority of sensation is
      processed through it. In this study, experienced drivers (ED) and inexperienced
      drivers (ID) were compared concerning scan path on a racetrack. Our intention was
      to study the problem that within each individual test group, similarities exist
      regarding the view of a complex and dynamic sequence. Furthermore, we analysed
      the concurrences in the scan path between the two compared test groups and
      whether we could verify a learning process for the ID. PROBANDS, MATERIALS, AND
      METHODS: The eye movement and scan path registrations of the eight probands (four
      ED and four ID) were measured with an eye tracking system based on the corneal
      reflex method. On the racetrack, the scan path of each proband was recorded with
      the eye tracking system and was analysed by special software. Therefore, the
      important objects were divided into areas of interest (AOI). RESULTS: The
      fixation duration results of the ID compared with the ED showed a 16.7% shorter
      fixation duration. The relative frequency of the scan path of the four most
      important AOI in bend 1 of the racetrack showed a significant difference
      (ED=78.85%; ID=30.25). The transition matrix showed a zero in all cell for 75% of
      the ED and 30.56% of the ID. The costs in the string editing for converting the
      comparing string in the reference string showed, on average, 12.5 costs for the
      ED and 50 costs for the ID. The learning process of the ID was demonstrated with
      the transition matrix (the increase in zeros from lap 1 to lap 3 was about
      72.72%) and the relative frequency (an increase in observation of the four most
      important AOI from 20.76% to 34.76%). CONCLUSION: The results point to a learned
      scan path for the ED. Consequently, we were able to show an ideal scan path that
      emphasises a learning process for the ID.

PMID- 19588158
TI  - Recurrence and functional results after open versus conventional laparoscopic
      versus robot-assisted laparoscopic rectopexy for rectal prolapse: a case-control
      study.
AB  - PURPOSE: This study was designed to evaluate recurrence and functional outcome of
      three surgical techniques for rectopexy: open (OR), laparoscopic (LR), and robot
      assisted (RR). A case-control study was performed to study recurrence after the
      three operative techniques used for rectal procidentia. The secondary aim of this
      study was to examine the differences in functional results between the three
      techniques. MATERIALS AND METHODS: All consecutive patients who underwent a
      rectopexy between January 2000 and September 2006 enrolled in this study. Peri
      operative data were collected from patient records and functional outcome was
      assessed by telephonic questionnaire. RESULTS: Eighty-two patients (71 females,
      mean age 56.4 years) underwent a rectopexy for rectal procidentia. Nine patients
      (11%) had a recurrence; one (2%) after OR, four (27%) after LR, and four (20%)
      after RR. RR showed significantly higher recurrence rates when controlled for age
      and follow-up time compared to OR, (p = 0.027), while LR showed near-significant
      higher rates (p = 0.059). Functional results improved in all three operation
      types, without a difference between them. CONCLUSIONS: LR and RR are adequate
      procedures but have a higher risk of recurrence. A RCT is needed assessing the
      definitive role of (robotic assistance in) laparoscopic surgery in rectopexy.

PMID- 19588160
TI  - Predictive feedback in human simulated pendulum balancing.
AB  - In studies of human balance, it is common to fit stimulus-response data by tuning
      the time-delay and gain parameters of a simple delayed feedback model. Many
      interpret this fitted model, a simple delayed feedback model, as evidence that
      predictive processes are not required to explain existing data on standing
      balance. However, two questions lead us to doubt this approach. First, does
      fitting a delayed feedback model lead to reliable estimates of the time-delay?
      Second, can a non-predictive controller provide an explanation compatible with
      the independently estimated time delay? For methodological and experimental
      clarity, we study human balancing of a simulated inverted pendulum via joystick
      and screen. A two-step approach to data analysis is used: firstly a non
      parametric model--the closed-loop impulse response--is estimated from the
      experimental data; second, a parametric model is fitted to the non-parametric
      impulse-response by adjusting time-delay and controller parameters. To support
      the second step, a new explicit formula relating controller parameters to closed
      loop impulse response is derived. Two classes of controller are investigated
      within a common state-space context: non-predictive and predictive. It is found
      that the time-delay estimate arising from the second step is strongly dependent
      on which controller class is assumed; in particular, the non-predictive control
      assumption leads to time-delay estimates that are smaller than those arising from
      the predictive assumption. Moreover, the time-delays estimated using the non
      predictive control assumption are not consistent with a lower-bound on the time
      delay of the non-parametric model whereas the corresponding predictive result is
      consistent. Thus while the goodness of fit only marginally favoured predictive
      over non-predictive control, if we add the additional constraint that the model
      must reproduce the non-parametric time delay, then the non-predictive control
      model fails. We conclude (1) the time-delay should be estimated independently of
      fitting a low order parametric model, (2) that balance of the simulated inverted
      pendulum could not be explained by the non-predictive control model and (3) that
      predictive control provided a better explanation than non-predictive control.

PMID- 19588159
TI  - Parvalbumin-positive GABAergic interneurons are increased in the dorsal
      hippocampus of the dystrophic mdx mouse.
AB  - Duchenne muscular dystrophy (DMD) is characterized by variable alterations of the
      dystrophin gene and by muscle weakness and cognitive impairment. We postulated an
      association between cognitive impairment and architectural changes of the
      hippocampal GABAergic system. We investigated a major subpopulation of GABAergic
      neurons, the parvalbumin-immunopositive (PV-I) cells, in the dorsal hippocampus
      of the mdx mouse, an acknowledged model of DMD. PV-I neurons were quantified and
      their distribution was compared in CA1, CA2, CA3, and dentate gyrus in wild-type
      and mdx mice. The cell morphology and topography of PV-I neurons were maintained.
      Conversely, the number of PV-I neurons was significantly increased in the mdx
      mouse. The percent increase of PV-I neurons was from 45% for CA2, up to 125% for
      the dentate gyrus. In addition, the increased parvalbumin content in the mdx
      hippocampus was confirmed by Western blot. A change in the hippocampus processing
      abilities is the expected functional counterpart of the modification displayed by
      PV-I GABAergic neurons. Altered hippocampal functionality can be responsible for
      part of the cognitive impairment in DMD.

PMID- 19588161
TI  - Management of isolated spontaneous dissection of superior mesenteric artery.
AB  - PURPOSE: Our objectives were to clarify the management of isolated spontaneous
      dissection of the superior mesenteric artery (DSMA). METHODS: We reviewed seven
      patients diagnosed as having DSMA from 2002 to 2007 (group A). Simultaneously, we
      analyzed 50 cases of DSMA previously reported in the literature between 2000 and
      2008 (group B). In each group, clinical presentation, Sakamoto's classification,
      imaging appearances, need for emergent surgery, failure of medical management,
      and long-term outcome were analyzed. RESULTS: In group A, according to Sakamoto's
      classification, there were two type I, two type II, and three type III. Two
      patients needed surgery (one type II, one type III). In group B, according to
      Sakamoto's classification, there were seven type I, five type II, 14 type III,
      and six type IV. Intestinal revascularization was necessary for 21 patients,
      especially for types II and III, while medical management was more frequent for
      types I and IV. We identified four indications for intestinal revascularization:
      acute mesenteric ischemia with mesenteric thrombosis, arterial rupture, chronic
      mesenteric ischemia with superior mesenteric artery (SMA) stenosis, and SMA
      dissecting aneurysm of at least 2 cm in diameter. If abdominal pain lasts for
      more than 1 week, types I and IV were able to be medically managed, whereas
      intestinal revascularization has to be considered in types II and III.
      CONCLUSION: Patients with symptoms lasting for more than 1 week, aneurysmal
      dilatation more than 2 cm in diameter, and SMA stenosis are suitable candidates
      for surgical management.

PMID- 19588163
TI  - Overexpression of an Arabidopsis gene encoding a subtilase (AtSBT5.4) produces a
      clavata-like phenotype.
AB  - Arabidopsis thaliana encodes 56 subtilisin-like serine proteases (subtilases),
      and some are involved in the proteolytic processing of plant peptide hormones.
      Here, we have investigated the role of one subtilase, AtSBT5.4, in whole plant
      physiology by examining gain- or loss-of-function phenotypes. Knockouts of
      AtSBT5.4 had no apparent phenotype; however, overexpression produced a clavata
      like phenotype with fasciated inflorescence stems and compounded terminal buds.
      Production of the phenotype depended on the enzymatic activity of the subtilase,
      because substitution of serine at the active site abolished the overexpression
      phenotype. When AtSBT5.4 was overexpressed in a clavata3 mutant background, a
      novel phenotype was produced suggesting that AtSBT5.4 interacts with the clavata
      signaling pathway. However, AtSBT5.4 did not cleave CLAVATA3 (CLV3) or a
      fluorogenic peptide representing the putative cleavage site in CLV3 under in
      vitro conditions suggesting that the interaction in vivo does not involve the
      cleavage of CLV3. Overexpression of AtSBT5.4 in a wuschel (wus) background
      suppressed the AtSBT5.4 overexpression phenotype indicating that WUS function is
      required for the AtSBT5.4 overexpression phenotype.

PMID- 19588162
TI  - Hybrid NOTES transvaginal cholecystectomy: operative and long-term results after
      18 cases.
AB  - PURPOSE: Natural orifice transluminal endoscopic surgery (NOTES) is a novel
      technique that aims at reducing or abolishing skin incisions and potentially also
      postoperative pain. The purpose of this study was to analyse operative and long
      term results of a series of hybrid transvaginal cholecystectomy. MATERIALS AND
      METHODS: Between July 2007 and May 2009, transvaginal NOTES cholecystectomy for
      symptomatic cholelithiasis was performed by a hybrid technique in 18 women (mean
      age 54 years), including four women with a body mass index >30 kg/m(2).
      Dissection was conducted in the first four cases by a round-tip unipolar
      electrode (UE) introduced through the operative channel of the endoscope coming
      from the vagina and in the last 14 cases by a ultrasonic scalpel (US) introduced
      through a 5-mm abdominal port. The short-term outcomes and the long-term results
      of the two methods were compared. RESULTS: The transvaginal approach entailed no
      intraoperative complication and no conversion. The overall mean duration of
      procedures was 75 min (range 40-190). In the first four cases (UE), the operating
      time was 148 min (range 140-190), whilst in the last 14 (US), it was considerably
      shorter, 53 min (range 40-60, p < 0.01). We experienced one biliary leak in the
      UE group, whilst morbidity with US was nil (p < 0.005). The biliary leak healed
      in 7 days with nasobiliary drainage. No other complications were encountered in
      either group. The mean follow-up was 12 months (range 1-22), and none of the
      patients has complained of dyspareunia or other colpotomy-related complications
      so far. CONCLUSIONS: Until specifically designed endoscopic tools are available
      for NOTES, the hybrid technique with US dissection conducted through a 5-mm port
      should be preferred in transvaginal cholecystectomy in order to shorten the
      duration of surgery and make this approach effective, safe and reproducible.
      After a mean follow-up of 1 year, none of our patients has complained of any
      problem related to transvaginal approach.

PMID- 19588164
TI  - Involvement of centrosomes in nuclear irregularity of thyroid carcinoma cells.
AB  - Nuclear irregularities including nuclear pseudoinclusions and nuclear grooves are
      characteristic of papillary thyroid carcinoma cells and are regarded as important
      diagnostic clues in histopathology. We observed nuclear features of thyroid
      carcinoma cell lines (KTC-1 and TPC-1) in various culture conditions and
      performed immunocytochemical examinations for cytoskeleton molecules to clarify
      the morphogenesis of thyroid carcinoma nuclei. We found that nuclear
      irregularities presenting as bean-like nuclei (BLNs) and donut-like nuclei (DLNs)
      appeared in cells from confluent cultures, but not in cells from sparse cultures.
      On immunocytofluorescence analyses, clusters of gamma-tubulin, representing a
      centrosome, frequently localized at the indentation of BLNs or in the hole of
      DLNs of thyroid carcinoma cells. In conclusion, we suggest that cell-to-cell
      contact may affect nuclear changes such as BLNs and DLNs in cancer cell lines and
      that centrosomes may be involved in the morphogenetic process of these nuclear
      changes.

PMID- 19588165
TI  - Antenatal treatment in two Dutch families with pyridoxine-dependent seizures.
AB  - Incidental reports suggest that antenatal treatment of pyridoxine dependent
      seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two
      families with PDS are reported, both with two affected siblings. Antenatal
      treatment with pyridoxine was instituted during the second pregnancy in each
      family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively).
      Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12
      (Family B) years of age were compared between the untreated and treated child
      within each family. Meconium-stained amniotic fluid was present in both first
      pregnancies and abnormal foetal movements were noticed in one. In the treated
      infants, pregnancy and birth were uncomplicated. In family A, postnatal
      pyridoxine supplementation prevented neonatal seizures. Both children in family A
      were hypotonic and started walking after 2 years of age; both had white matter
      changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in
      the antenatally untreated and treated child, respectively. The second child in
      family B developed seizures on the seventh day, because pyridoxine maintenance
      therapy had not been instituted after birth. Seizures responded rapidly to
      pyridoxine supplementation. MRI showed large ventricles and a mega cisterna
      magna. IQ was 80 and 106 in the antenatally untreated and treated child
      respectively. Both children had normal motor development. These results suggest
      that antenatal pyridoxine supplementation may be effective in preventing
      intrauterine seizures, decreasing the risk of complicated birth and improving
      neurodevelopmental outcome in PDS.

PMID- 19588166
TI  - Experimentally promising antischistosomal drugs: a review of some drug candidates
      not reaching the clinical use.
AB  - Schistosomiasis is a chronic parasitic disease affecting about 207 million people
      in the world. It still represents a major health problem in many tropical and sub
      tropical countries as well as for travelers from developed countries. Control of
      the disease depends mainly on chemotherapy, with praziquantel becoming the
      exclusive drug. Extensive use of praziquantel with concerns about the possibility
      of drug resistance development, unavailability of an applicable vaccine, and the
      absence of a reasonable alternative to praziquantel all represent a real
      challenge. One of the suggested solutions is to exploit the advantages of
      compounds that proved efficacious at the experimental level with a good safety
      profile. These may undergo further investigations for the sake of developing
      their antischistosomal properties or to incorporate them in combination
      therapies. Chemotherapy literature is redundant with a huge number of compounds
      screened for their schistosomicidal properties. However, only a few of these may
      act as drug leads that could be promising in the development of a therapeutic
      reserve for schistosomiasis. The present paper reviews previous studies carried
      out on some of these compounds.

PMID- 19588168
TI  - Integrin-mediated adhesion and stem-cell-niche interactions.
AB  - The regulation of stem cell behavior and maintenance typically involves the
      integration of both intrinsic and extrinsic cues. One such external cue, integrin
      mediated cell adhesion to the extracellular matrix, plays an important part in
      regulating stem cell function and maintenance. In particular, integrins help
      define and shape the microenvironment in which stem cells are found: the stem
      cell niche. Integrins have a diverse array of roles in this context including
      homing of stem cells to their niche, maintaining stem cells in the niche,
      developing stem-cell-niche architecture, regulating stem cell proliferation and
      self renewal, and finally, controlling the orientation of dividing stem cells.
      Because of their various roles in directing stem cell behavior, integrin-mediated
      adhesion and signaling in the niche have been implicated in processes that
      underlie cancer progression and metastasis.

PMID- 19588167
TI  - A diagnostically useful 200-kDa protein is secreted through the surface pores of
      the filarial parasite Setaria digitata.
AB  - The excretory/secretory (ES) materials from filarial parasites form an important
      tool for immunodiagnosis of filariasis. We have raised monoclonal antibodies
      against ES proteins isolated from the medium incubated with live adult bovine
      filarial parasite Setaria digitata. The hybridoma were cloned and characterised
      with respect to the individual proteins of the ES materials. A secretory
      glycoprotein with molecular weight 200-kDa (gp200) was purified, localised and
      characterised using the specific monoclonal antibodies raised against it. The
      immunolocalisation study clearly showed that the protein is secreted out through
      the pores on the surface of both male and female parasites. The gp200 on reduced
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed dissociation
      into 11- to 66-kDa 'ladder' polypeptides, and all of them could be identified
      with the same monoclonal antibody. The gp200 is normally shed along with the ES
      materials. The screening of human sera samples using the monoclonal antibodies
      give promising results which showed that gp200 could be a potent candidate
      protein for the immunodiagnosis of filariasis by the method of antigen detection.

PMID- 19588170
TI  - Intrapersonal and interpersonal dimensions of cancer perception: a confirmatory
      factor analysis of the cancer experience and efficacy scale (CEES).
AB  - PURPOSE: Sociocultural factors influence psychological adjustment to cancer in
      Asian patients in two major ways: prioritization of relationships over individual
      orientations and belief in the efficacy of interpersonal cooperation. We derived
      and validated among Chinese colorectal cancer (CRC) patients an instrument
      assessing cancer perceptions to enable the study of the sociocultural processes.
      PATIENTS AND METHODS: Qualitative interviews (n = 16) derived 15 items addressing
      interpersonal experience in Chinese CRC patients' adjustment. These 15 items and
      18 corresponding self-referent items were administered to 166 Chinese CRC
      survivors and subjected to exploratory factor analysis (EFA) to establish the
      initial scale structure and reliability. The final 29 items, together with other
      psychometric measures, were administered to a second cohort of 215 CRC patients
      and subjected to confirmatory factor analysis (CFA). RESULTS: EFA (63.35% of the
      total variance) extracted six factors: personal strain, socioeconomic strain,
      emotional strain, personal efficacy, collective efficacy, and proxy efficacy. CFA
      confirmed the psychometric structure [chi (2)(df) = 702.91(368); Comparative Fit
      Index = 0.95; Nonnormed Fit Index = 0.94; Incremental Fit Index = 0.95;
      standardized root mean square residual = 0.08] of the six factors by using a
      model with two latent factors: experience and efficacy. All subscales were
      reliable (alpha = 0.76-0.92). Appropriate correlations with adjustment outcomes
      (symptom distress, psychological morbidity, and subjective well-being),
      optimistic personalities, and social relational quality indicated its convergent
      and divergent validity. Known group comparisons (i.e., age, active treatment, and
      colostomy) showed its clinical utility. CONCLUSION: The cancer experience and
      efficacy scale is a valid multidimensional instrument for assessing intrapersonal
      and interpersonal dimensions of cancer experience in Asian patients, potentiating
      existing patient-reported outcome measures.

PMID- 19588169
TI  - Can prompt treatment of childhood UTI prevent kidney scarring?
AB  - The aim of the study reported here was to determine whether kidney scarring after
      urinary tract infections (UTI) in children can be prevented and to identify the
      risk factors for developing scars. We identified children in the Northern health
      region of the UK who had been seen to develop scars, identified as new defects on
      dimercapto-succinic acid (DMSA) scanning. Risk factors were sought by reviewing
      case-notes and interviews with parents. Twenty girls were identified whose new
      scarring was strongly associated with having both vesicoureteric reflux (VUR) and
      a UTI (p = 0.0001); 19/23 (83%) of kidneys exposed to both of these factors
      developed scars. Children were much more likely to be febrile (94 vs. 30%, p <
      0.0001) or unwell (82 vs. 10%, p < 0.0001) during their earlier UTIs when they
      were of median age 2.8 years (range 0.3-5.0 years) and did not scar, compared to
      their later UTIs at age 7.3 years (1.2-12.5 years), when they did scar. However,
      most patients were treated within 1 day of their symptoms for their early UTIs,
      compared to a wait >or=7 days for later UTIs (p = 0.001). Being febrile or unwell
      during a UTI does not predict the development of scars, but prompt treatment
      appears to prevent scarring in children with VUR.

PMID- 19588171
TI  - Biomechanical analysis of expansion screws and cortical screws used for ventral
      plate fixation on the cervical spine.
AB  - Compared to bicortical screws, the surgical risk of injuring intraspinal
      structures can be minimized with the use of monocortical screws. However, this
      reduction should not be achieved at the expense of the stability of the fixation.
      With monocortical stabilization, the expansion screws have the potential of
      absorbing high loads. Therefore, they are expected to be a suitable alternative
      to bicortical screws for revision surgeries and in osteoporotic bone. The purpose
      of this in vitro study was to investigate the stiffness of the two screw-plate
      systems used for ventral stabilization of the cervical spine, by focusing on the
      suitability of expansion screws as tools for revision treatments. The study was
      conducted in ten functional units of human cervical spines. The device sample
      stiffness was determined for four conditions using a turning moment of 2.25 N m
      each around one of the three principle axes. The conditions were native,
      destabilized, primarily stabilized with one of the screw-plate systems, followed
      by secondary stabilization using the expansion screw implant. The stabilized
      samples achieved a comparable, in most cases higher stiffness than the native
      samples. The samples undergoing secondary stabilization using expansion screws
      tend to display greater stiffness for all three axes compared to the primarily
      stabilized samples. The achieved tightening moment of the screws was higher than
      the one achieved with primary fixation. Both plates revealed similar primary
      stability. Revision surgeries with secondary instrumentation achieve a high
      stiffness of the screwed up segments. Monocortical expansion screws combined with
      a trapezoidal plate allow ventral stabilization of the cervical spine that is
      comparable to the plate fixation using bicortical screws.

PMID- 19588172
TI  - QM/MM investigation into binding of square-planar platinum complexes to DNA
      fragments.
AB  - A series of calculations employing hybrid quantum mechanics/molecular mechanics
      methods to explore the binding of square-planar complexes to fragments of DNA are
      reported. Methylated analogues of the parent compound cis-[Pt(en)Cl(2)], where en
      is ethylenediamine, show considerable variation in in vitro cytotoxicity
      depending on the number and position of methyl groups. Calculations reveal
      variations in the structure and the binding energy of adducts to single- and
      double-stranded fragments of DNA. Most such variations are relatively small, but
      the introduction of three or four methyls on nitrogen of ethylenediamine
      significantly changes the structure and reduces the binding energy, owing to
      replacement of strong N-H...O interactions by much weaker C-H...O contacts. Close
      correlation between measured activity and binding energy is observed, whereas
      little or no correlation is found with structural parameters or with estimates of
      the octanol/water partition coefficient, either alone or in combination via
      multiple linear regression.

PMID- 19588173
TI  - A study on the interaction between 5-Methyluridine and human serum albumin using
      fluorescence quenching method and molecular modeling.
AB  - This work was designed to study the interaction between 5-Methyluridine and human
      serum albumin (HSA) under simulative physiological conditions using fluorescence
      spectroscopy in combination with molecular modeling technique for the first time.
      Static quenching was suggested by the fluorescence measurement. The binding
      constants (K) were calculated according to the relevant fluorescence data at
      different conditions including temperature. Thermodynamic parameter, different
      conditions including temperature to determine enthalpy change and entropy change,
      indicating the hydrophobic force played a major role in the binding interaction
      between 5-Methyluridine and HSA. The experimental result was in correspondence
      with molecular modeling theory.

PMID- 19588174
TI  - Cation recognition of thiacalix[2]thianthrene and p-tert
      butylthiacalix[2]thianthrene and their conformers and complexes with Zn(II),
      Cd(II) and Hg(II): a theoretical investigation.
AB  - The structures of thiacalix[2]thianthrene, p-tert-butylthiacalix[2]thianthrene
      and their complexes with Zn(2+), Cd(2+) and Hg(2+) were obtained using
      B3LYP/LanL2DZ and HF/LanL2DZ calculations. The structures of the most stable
      conformers of thiacalix[2]thianthrene and p-tert-butylthiacalix[2]thianthrene
      optimized at either the B3LYP/LanL2DZ or HF/LanL2DZ level are in good agreement
      with their corresponding X-ray crystallographic structures. The binding energies
      of cations, Zn(2+), Cd(2+) and Hg(2+) to thiacalix[2]thianthrene and to p-tert
      butylthiacalix[2]thianthrene conformers, and the thermodynamic properties of
      their associations were obtained. The relative selectivities of both
      thiacalix[2]thianthrene and thiacalix[2]thianthrene conformer are in same order:
      Zn(2+) >> Hg(2+) > Cd(2+).

PMID- 19588175
TI  - Grey squirrels (Sciurus carolinensis) show a feature-negative effect specific to
      social learning.
AB  - Previous laboratory studies on social learning suggest that some animals can
      learn more readily if they first observe a conspecific demonstrator perform the
      task unsuccessfully and so fail to obtain a food reward than if they observe a
      successful demonstrator that obtains the food. This effect may indicate a
      difference in how easily animals are able to associate different outcomes with
      the conspecific or could simply be the result of having food present in only some
      of the demonstrations. To investigate we tested a scatter-hoarding mammal, the
      eastern grey squirrel, on its ability to learn to choose between two pots of food
      after watching a conspecific remove a nut from one of them on every trial.
      Squirrels that were rewarded for choosing the opposite pot to the conspecific
      chose correctly more frequently than squirrels rewarded for choosing the same pot
      (a feature-negative effect). Another group of squirrels was tested on their
      ability to choose between the two pots when the rewarded option was indicated by
      a piece of card. This time, squirrels showed no significant difference in their
      ability to learn to choose the same or the opposite pot. The results add to
      anecdotal reports that grey squirrels can learn by observing a conspecific and
      suggest that even when all subjects are provided with demonstrations with the
      same content, not all learning occurs equally. Prior experience or expectations
      of the association between a cue (a conspecific) and food influences what can be
      learned through observation whilst previously unfamiliar cues (the card) can be
      associated more readily with any outcome.

PMID- 19588176
TI  - Attributing attention: the use of human-given cues by domestic horses (Equus
      caballus).
AB  - Recent research has shown that domestic dogs are particularly good at determining
      the focus of human attention, often outperforming chimpanzees and hand-reared
      wolves. It has been suggested that the close evolutionary relationship between
      humans and dogs has led to the development of this ability; however, very few
      other domestic species have been studied. We tested the ability of 36 domestic
      horses to discriminate between an attentive and inattentive person in determining
      whom to approach for food. The cues provided were body orientation, head
      orientation or whether the experimenters' eyes were open or closed. A fourth,
      mixed condition was included where the attentive person stood with their body
      facing away from the subjects but their head turned towards the subject while the
      inattentive person stood with their body facing the subject but their head turned
      away. Horses chose the attentive person significantly more often using the body
      cue, head cue, and eye cue but not the mixed cue. This result suggests that
      domestic horses are highly sensitive to human attentional cues, including gaze.
      The possible role of evolutionary and environmental factors in the development of
      this ability is discussed.

PMID- 19588177
TI  - Pelvic CT angiography: application to blunt trauma using 64MDCT.
AB  - The evolution of multi-row detector computed tomography (MDCT) technology has
      resulted in evolving applications of CT angiography (CTA) in the trauma setting.
      In patients with significant blunt pelvic injuries, the immediate diagnosis and
      characterization of vascular injuries is of significant import given their
      morbidity and mortality in this patient population. The application of MDCT
      technology, specifically 64MDCT, to pelvic CTA is useful in evaluating for
      potential vascular injuries and may be integrated into admission trauma imaging
      in order to triage patients with blunt pelvic trauma to appropriate emergent
      intervention. This paper will discuss the use of pelvic CTA in blunt pelvic
      trauma and its utility in detecting and characterizing vascular injury, including
      the differentiation of arterial from venous hemorrhage. Protocol considerations
      in pelvic CTA using 64MDCT technology will be detailed as well as the integration
      of pelvic CTA into torso CT trauma protocols.

PMID- 19588178
TI  - Sleepiness and sleep-related accidents in commercial bus drivers.
AB  - INTRODUCTION: Professional drivers are at high risk of sleepiness due to a
      combination of factors including shift work and obstructive sleep apnea/hypopnea
      syndrome (OSAHS), and sleepiness in professional drivers is highly dangerous.
      This study aimed to determine the prevalence of excessive daytime sleepiness and
      accident rates in bus drivers. MATERIALS AND METHODS: Drivers employed at bus
      depots within 30 miles of Edinburgh were given a sleep questionnaire. One
      thousand eight hundred fifty-four drivers were approached, and 677 (37%; 25
      female) completed questionnaires with a 97% response rate among the 456 given
      directly to drivers by the researcher. RESULTS: Of the responding drivers, 133
      (20% of total, 19% of researcher-delivered questionnaires) reported an Epworth
      sleepiness score >10. Eight percent of drivers reported falling asleep at the
      wheel at least once/month, and 7% having an accident, and 18% a near-miss
      accident due to sleepiness while working. DISCUSSION: This study shows a
      concerningly high rate of sleepiness and sleep-related accidents among bus
      drivers. Screening for OSAHS among commercial drivers needs to be seriously
      evaluated with some urgency.

PMID- 19588180
TI  - Landscape-scale distribution and persistence of genetically modified oilseed rape
      (Brassica napus) in Manitoba, Canada.
AB  - BACKGROUND, AIM AND SCOPE: Genetically modified herbicide-tolerant (GMHT) oilseed
      rape (OSR; Brassica napus L.) was approved for commercial cultivation in Canada
      in 1995 and currently represents over 95% of the OSR grown in western Canada.
      After a decade of widespread cultivation, GMHT volunteers represent an increasing
      management problem in cultivated fields and are ubiquitous in adjacent ruderal
      habitats, where they contribute to the spread of transgenes. However, few studies
      have considered escaped GMHT OSR populations in North America, and even fewer
      have been conducted at large spatial scales (i.e. landscape scales). In
      particular, the contribution of landscape structure and large-scale anthropogenic
      dispersal processes to the persistence and spread of escaped GMHT OSR remains
      poorly understood. We conducted a multi-year survey of the landscape-scale
      distribution of escaped OSR plants adjacent to roads and cultivated fields. Our
      objective was to examine the long-term dynamics of escaped OSR at large spatial
      scales and to assess the relative importance of landscape and localised factors
      to the persistence and spread of these plants outside of cultivation. MATERIALS
      AND METHODS: From 2005 to 2007, we surveyed escaped OSR plants along roadsides
      and field edges at 12 locations in three agricultural landscapes in southern
      Manitoba where GMHT OSR is widely grown. Data were analysed to examine temporal
      changes at large spatial scales and to determine factors affecting the
      distribution of escaped OSR plants in roadside and field edge habitats within
      agricultural landscapes. Additionally, we assessed the potential for seed
      dispersal between escaped populations by comparing the relative spatial
      distribution of roadside and field edge OSR. RESULTS: Densities of escaped OSR
      fluctuated over space and time in both roadside and field edge habitats, though
      the proportion of GMHT plants was high (93-100%). Escaped OSR was positively
      affected by agricultural landscape (indicative of cropping intensity) and by the
      presence of an adjacent field planted to OSR. Within roadside habitats, escaped
      OSR was also strongly associated with large-scale variables, including road
      surface (indicative of traffic intensity) and distance to the nearest grain
      elevator. Conversely, within field edges, OSR density was affected by localised
      crop management practices such as mowing, soil disturbance and herbicide
      application. Despite the proximity of roadsides and field edges, there was little
      evidence of spatial aggregation among escaped OSR populations in these two
      habitats, especially at very fine spatial scales (i.e. <100 m), suggesting that
      natural propagule exchange is infrequent. DISCUSSION: Escaped OSR populations
      were persistent at large spatial and temporal scales, and low density in a given
      landscape or year was not indicative of overall extinction. As a result of
      ongoing cultivation and transport of OSR crops, escaped GMHT traits will likely
      remain predominant in agricultural landscapes. While escaped OSR in field edge
      habitats generally results from local seeding and management activities occurring
      at the field-scale, distribution patterns within roadside habitats are determined
      in large part by seed transport occurring at the landscape scale and at even
      larger regional scales. Our findings suggest that these large-scale anthropogenic
      dispersal processes are sufficient to enable persistence despite limited natural
      seed dispersal. This widespread dispersal is likely to undermine field-scale
      management practices aimed at eliminating escaped and in-field GMHT OSR
      populations. CONCLUSIONS: Agricultural transport and landscape-scale cropping
      patterns are important determinants of the distribution of escaped GM crops. At
      the regional level, these factors ensure ongoing establishment and spread of
      escaped GMHT OSR despite limited local seed dispersal. Escaped populations thus
      play an important role in the spread of transgenes and have substantial
      implications for the coexistence of GM and non-GM production systems.
      RECOMMENDATIONS AND PERSPECTIVES: Given the large-scale factors driving the
      spread of escaped transgenes, localised co-existence measures may be
      impracticable where they are not commensurate with regional dispersal mechanisms.
      To be effective, strategies aimed at reducing contamination from GM crops should
      be multi-scale in approach and be developed and implemented at both farm and
      landscape levels of organisation. Multiple stakeholders should thus be consulted,
      including both GM and non-GM farmers, as well as seed developers, processors,
      transporters and suppliers. Decisions to adopt GM crops require thoughtful and
      inclusive consideration of the risks and responsibilities inherent in this new
      technology.

PMID- 19588181
TI  - Artificial rearing of infant mice leads to n-3 fatty acid deficiency in cardiac,
      neural and peripheral tissues.
AB  - The ability to control the fatty acid content of the diet during early
      development is a crucial requirement for a one-generation model of
      docosahexaenoic acid (DHA; 22:6n3) deficiency. A hand feeding method using
      artificial rearing (AR) together with sterile, artificial milk was employed for
      feeding mice from postnatal day 2-15. The pups were fed an n-3 fatty acid
      adequate (3% alpha-linolenic acid (LNA; 18:3n3) + 1% 22:6n3) or a deficient diet
      (0.06% 18:3n3) with linoleic acid (LA; 18:2n6) as the only dietary source of
      essential fatty acids by AR along with a dam-reared control group (3.1% 18:3n3).
      The results indicate that restriction of n-3 fatty acid intake during postnatal
      development leads to markedly lower levels of brain, retinal, liver, plasma and
      heart 22:6n3 at 20 weeks of age with replacement by docosapentaenoic acid (DPAn6;
      22:5n6), arachidonic acid (ARA; 20:4n6) and docosatetraenoic acid (DTA; 22:4n6).
      A detailed analysis of phospholipid classes of heart tissue indicated that
      phosphatidylethanolamine, phosphatidylcholine and cardiolipin were the major
      repositories of 22:6n3, reaching 40, 29 and 15%, respectively. A novel heart
      cardiolipin species containing four 22:6n3 moieties is described. This is the
      first report of the application of artificially rearing to mouse pup nutrition;
      this technique will facilitate dietary studies of knockout animals as well as the
      study of essential fatty acid (EFA) functions in the cardiovascular, neural and
      other organ systems.

PMID- 19588182
TI  - Hepatic lipid metabolism response to dietary fatty acids is differently modulated
      by PPARalpha in male and female mice.
AB  - BACKGROUND: In human beings, women are at lower risk of cardiovascular diseases,
      and respond differently from men to dietary fatty acids. AIM: The aim of the
      present study was to investigate (i) the influence of gender on the response of
      lipid metabolism to dietary n-3 PUFA, and (ii) the contribution of PPARalpha to
      this response. METHODS: Male and female mice, wild-type (WT) and PPARalpha-null
      (KO), were fed on diets rich in either saturated FA (SFA) or 18:3 n-3 (ALA).
      Lipid composition, mRNA levels and certain activities of key enzymes and major
      transcription factors were determined in the liver. WT mice were slightly
      affected by dietary FA. However, in WT female mice, but not in males, mRNA levels
      of PPARalpha-dependent genes (L-FABP, ACO) were higher in the mice fed on the ALA
      rich diet. When compared to WT mice, KO female mice exhibited a decreased
      lipogenesis capacity (40% lower FAS, ACC, and SREBP-1c mRNA level), whereas KO
      males showed a decrease in peroxisomal beta-oxidation (activity and expression of
      ACO reduced by 20 and 40%, respectively). When compared to SFA-fed KO mice,
      steatosis was twice lower in KO mice fed on ALA, despite the absence of dietary
      effect on plasma TG, CPT1 and ACO activities, or ACC and FAS expression. Besides,
      in mice on the SFA diet, steatosis was alleviated in females, and CPT1 expression
      was up-regulated to a higher extent in females than in males (2.7- and 3.6-fold,
      respectively, as compared to the corresponding WT groups). CONCLUSIONS: Our data
      suggests estrogen to modulate the regulation of hepatic lipid metabolic pathway
      by dietary fatty acids. Besides, PPARalpha invalidation resulted in unexpected
      regulations by ALA of its known targets and was compensated partly in females,
      which was therefore less sensitive to the detrimental effects of a SFA-rich diet.

PMID- 19588183
TI  - Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte
      hypertrophy through the Akt/GSK-3beta/mTOR signaling pathway.
AB  - Several studies have implicated the renin angiotensin system in the cardiac
      hypertrophy induced by thyroid hormone. However, whether Angiotensin type 1
      receptor (AT1R) is critically required to the development of T3-induced
      cardiomyocyte hypertrophy as well as whether the intracellular mechanisms that
      are triggered by AT1R are able to contribute to this hypertrophy model is
      unknown. To address these questions, we employed a selective small interfering
      RNA (siRNA, 50 nM) or an AT1R blocker (Losartan, 1 microM) to evaluate the
      specific role of this receptor in primary cultures of neonatal cardiomyocytes
      submitted to T3 (10 nM) treatment. The cardiomyocytes transfected with the AT1R
      siRNA presented reduced mRNA (90%, P < 0.001) and protein (70%, P < 0.001)
      expression of AT1R. The AT1R silencing and the AT1R blockade totally prevented
      the T3-induced cardiomyocyte hypertrophy, as evidenced by lower mRNA expression
      of atrial natriuretic factor (66%, P < 0.01) and skeletal alpha-actin (170%, P <
      0.01) as well as by reduction in protein synthesis (85%, P < 0.001). The
      cardiomyocytes treated with T3 demonstrated a rapid activation of Akt/GSK
      3beta/mTOR signaling pathway, which was completely inhibited by the use of PI3K
      inhibitors (LY294002, 10 microM and Wortmannin, 200 nM). In addition, we
      demonstrated that the AT1R mediated the T3-induced activation of Akt/GSK
      3beta/mTOR signaling pathway, since the AT1R silencing and the AT1R blockade
      attenuated or totally prevented the activation of this signaling pathway. We also
      reported that local Angiotensin I/II (Ang I/II) levels (120%, P < 0.05) and the
      AT1R expression (180%, P < 0.05) were rapidly increased by T3 treatment. These
      data demonstrate for the first time that the AT1R is a critical mediator to the
      T3-induced cardiomyocyte hypertrophy as well as to the activation of Akt/GSK
      3beta/mTOR signaling pathway. These results represent a new insight into the
      mechanism of T3-induced cardiomyocyte hypertrophy, indicating that the Ang I/II
      AT1R-Akt/GSK-3beta/mTOR pathway corresponds to a potential mediator of the
      trophic effect exerted by T3 in cardiomyocytes.

PMID- 19588185
TI  - Involvement in bullying and depression in a 2-year follow-up in middle
      adolescence.
AB  - The main objective was to analyse whether involvement in bullying at school
      predicts depression, and whether depression predicts involvement in bullying in
      middle adolescence. A total of 2,070 15-year-old girls and boys in two Finnish
      cities were surveyed at ninth grade (age 15) at schools, and followed up 2 years
      later in the Adolescent Mental Health Cohort Study (AMHC). Depression was
      measured by a Finnish modification of the 13-item short Beck Depression
      Inventory. Involvement in bullying was elicited by three questions focusing on
      being a bully, being a victim to bullying, and being left alone by peers against
      one's wishes. Similar questions were posed at both time points. Statistical
      analyses were carried out using cross-tabulations with chi-square/Fisher's Exact
      Test statistics, and logistic regression. The results summarized that, both being
      a victim to bullying and being a bully predicted later depression among boys.
      Among girls, depression at T1 predicted victimisation at T2. Depression at T1
      predicted experience of being left alone at T2 among both sexes. It was concluded
      that victimisation to bullying may be a traumatising event that results in
      depression. However, depression also predicts experience of victimisation and of
      being left alone against one's wishes. Depression may impair an adolescent's
      social skills and self-esteem so that the adolescent becomes victimised by peers.
      However, depression may also distort and adolescent's experiences of social
      interactions.

PMID- 19588188
TI  - Diagnostic accuracy of CT colonography and optical colonoscopy evaluated using
      surgically resected specimens.
AB  - OBJECTIVE: The aim of this study was to clarify the diagnostic ability of CT
      colonography (CTC) using surgically resected specimens to avoid inaccuracy
      associated with optical colonoscopy (OC). SUBJECTS AND METHODS: CTC and OC were
      performed in 152 consecutive patients with colorectal cancer. Forty patients had
      simultaneous lesions other than the ones for which the surgery was intended, and
      these lesions were used as the gold standard. In 24 patients without stenosis,
      the sensitivity and positive predictive values (PPV) of CTC and OC were
      evaluated. In 16 patients with stenosis, the diagnostic ability of CTC for
      lesions located proximal to the stenosis was assessed. RESULTS: Sensitivity of
      CTC and OC was 81% and 66% (P = 0.16), and PPV was 90% and 100% (P = 0.13),
      respectively. For 22 lesions larger than 5 mm, the sensitivity of CTC and OCS was
      96% and 91% (P > 0.50), and PPV was 100% and 100%, respectively. In patients with
      stenosis, sensitivity and PPV were 89% and 80%, respectively. These results were
      not significantly different from those in patients without stenosis. CONCLUSIONS:
      CTC is a reliable modality for the diagnosis of colorectal polyps. It is also
      useful to evaluate the colon proximal to severe stenosis which could not be
      observed by OC.

PMID- 19588187
TI  - Pancreatic adenocarcinoma: a comparison of automatic bolus tracking and empirical
      scan delay.
AB  - BACKGROUND: To evaluate the efficacy of automatic bolus tracking in multidetector
      row CT (MDCT) for pancreatic adenocarcinoma as compared with standard scan delay
      using the fixed duration contrast injection technique. MATERIALS AND METHODS:
      Seventy-nine patients with pancreatic adenocarcinomas underwent three-phase
      enhanced CT with an individualized scan delay as determined by automatic bolus
      tracking (protocol 1) or an empiric scan delay (protocol 2). We evaluated
      enhancement of the aorta, portal vein, hepatic parenchyma, pancreatic parenchyma,
      and pancreatic adenocarcinoma during each phase. Two radiologists graded the
      conspicuity of pancreatic adenocarcinoma in the pancreatic parenchymal phase. The
      results for the different groups were statistically compared. RESULTS: Pancreatic
      parenchymal enhancement (mean +/- standard deviation, 100.2 HU +/- 17.6 vs. 88.5
      HU +/- 22.1; P < 0.05) and tumor-to-pancreas contrast (mean +/- standard
      deviation, 75.3 HU +/- 25.0 vs. 63.1 HU +/- 24.1; P < 0.05) were significantly
      greater in protocol 1 than in protocol 2 during pancreatic parenchymal phase.
      Qualitative results correlated well with quantitative results (reviewer 1: R (s)
      = 0.78, P < 0.001; reviewer 2: R (s) = 0.66, P < 0.001) CONCLUSION: The use of
      automatic bolus tracking with MDCT can significantly improve the degree of
      contrast enhancement in the pancreatic parenchyma and tumor-to-pancreas
      conspicuity.

PMID- 19588186
TI  - Morphological, bacterial, and secondary metabolite changes of Aplysina aerophoba
      upon long-term maintenance under artificial conditions.
AB  - The aim of this study was to analyze successional changes in the bacterial
      community over a period of 6 months of cultivation of Aplysina aerophoba sponges
      under different artificial cultivation conditions by use of denaturing gradient
      gel electrophoresis (DGGE). The cultivation conditions varied concerning the
      water temperature (20 +/- 2 degrees C and 25 +/- 2 degrees C) of the aquaria,
      additional illumination of one aquarium, and feeding of the sponges. Amplicons
      from DGGE separation of dominant colonizing or variably appearing bacteria were
      sequenced and aligned for taxonomical identification. In addition, secondary
      metabolites typically found in A. aerophoba were analyzed to investigate changes
      in the natural product profile during cultivation. The cultivation of sponges
      under any given condition did not lead to a depletion of their bacterial
      community in the course of the experiment. On the contrary, the distinctive set
      of associated bacteria was maintained in spite of a dramatic loss of biomass and
      morphological degradation during the cultivation period. Generally, all sequences
      obtained from the DGGE gels were related to bacteria of five phyla:
      Actinobacteria, Cyanobacteria, alpha-Proteobacteria, gamma-Proteobacteria, and
      Chloroflexi. Despite the overall stability of the bacterial community in A.
      aerophoba, an unambiguous variability was detected for the Cyanobacteria "A.
      aerophoba clone TK09". This variability was ascribed to the predominant light
      conditions. The analysis of the metabolic pattern revealed that the concentration
      of a class of characteristic-brominated compounds typically found in A.
      aerophoba, like aeroplysinin-1, aerophobin-1, aerophobin-2, and isofistularin-3,
      increased over the 6 months of cultivation.

PMID- 19588184
TI  - The endocannabinoid system and the regulation of neural development: potential
      implications in psychiatric disorders.
AB  - During brain development, functional neurogenesis is achieved by the concerted
      action of various steps that include the expansion of progenitor cells, neuronal
      specification, and establishment of appropriate synapses. Brain patterning and
      regionalization is regulated by a variety of extracellular signals and morphogens
      that, together with neuronal activity, orchestrate and regulate progenitor
      proliferation, differentiation, and neuronal maturation. In the adult brain,
      CB(1) cannabinoid receptors are expressed at very high levels in selective areas
      and are engaged by endocannabinoids, which act as retrograde messengers
      controlling neuronal function and preventing excessive synaptic activity. In
      addition, the endocannabinoid system is present at early developmental stages of
      nervous system formation. Recent studies have provided novel information on the
      role of this endogenous neuromodulatory system in the control of neuronal
      specification and maturation. Thus, cannabinoid receptors and locally produced
      endocannabinoids regulate neural progenitor proliferation and pyramidal
      specification of projecting neurons. CB(1) receptors also control axonal
      navigation, migration, and positioning of interneurons and excitatory neurons.
      Loss of function studies by genetic ablation or pharmacological blockade of CB(1)
      receptors interferes with long-range subcortical projections and, likewise,
      prenatal cannabinoid exposure induces different functional alterations in the
      adult brain. Potential implications of these new findings, such as the
      participation of the endocannabinoid system in the pathogenesis of
      neurodevelopmental disorders (e.g., schizophrenia) and the regulation of
      neurogenesis in brain depression, are discussed herein.

PMID- 19588189
TI  - Autologous platelet-rich plasma mixed with purified fat graft in aesthetic
      plastic surgery.
AB  - Platelet-rich plasma (PRP) is a platelet concentrate that has widely been used to
      accelerate the healing of soft and hard tissues. The preparation of PRP has been
      described by several authors. Preparation protocols vary from system to system,
      depending on the concentration of different integrating proteins. The objective
      of this article is to describe the principal use of PRP mixed with fat grafts in
      aesthetic plastic surgery.

PMID- 19588190
TI  - Conservative mastectomies.
AB  - Nowadays, oncological breast surgery has to be performed to maximize cosmetic
      results, and even mastectomies, when unavoidable, should conform to acceptable
      aesthetics. We investigated surgical approaches to skin-sparing mastectomies.
      Scar positioning and volume replacement were evaluated. We also discuss nipple
      sparing mastectomy (NSM), probably the most outstanding item in the current
      debate on breast shape preservation. We give suggestions for safe admission
      criteria and effective treatment.

PMID- 19588191
TI  - Shrub encroachment impacts the potential for multiple use conflicts on public
      land.
AB  - Public rangelands in North America are typically managed under a multiple use
      policy that includes livestock grazing and wildlife management. In this article
      we report on the landscape level extent of grassland loss to shrub encroachment
      in a portion of the Rocky Mountain Forest Reserve in southwestern Alberta,
      Canada, and review the associated implications for simultaneously supporting
      livestock and wildlife populations while maintaining range health on this
      diminishing vegetation type. Digitized aerial photographs of 12 km of valley
      bottom from 1958 and 1974 were co-registered to ortho-rectified digital imagery
      taken in 1998, and an un-supervised classification used to determine areas
      associated with grassland and shrubland in each year. Field data from 2002 were
      over-layed using GPS coordinates to refine the classification using a calibration
      validation procedure. Over the 40-year study period, open grasslands declined
      from 1,111 ha in 1958 to 465 ha in 1998, representing a 58% decrease. Using mean
      production data for grass and shrub dominated areas we then quantified aggregate
      changes in grazing capacity of both primary (grassland) and secondary (shrubland)
      habitats for livestock and wildlife. Total declines in grazing capacity from 1958
      to 1998 totaled 2,744 Animal Unit Months (AUMs) of forage (-39%), including a 58%
      decrease in primary (i.e., open grassland) range, which was only partly offset by
      the availability of 1,357 AUMs within less productive and less accessible
      shrubland habitats. Our results indicate shrub encroachment has been extensive
      and significantly reduced forage availability to domestic livestock and wildlife,
      and will increase the difficulty of conserving remaining grasslands. Although
      current grazing capacities remain marginally above those specified by regulated
      grazing policies, it is clear that continued habitat change and decreases in
      forage availability are likely to threaten the condition of remaining grasslands.
      Unless shrub encroachment is arrested or grassland restoration initiated,
      reductions in aggregate ungulate numbers may be necessary.

PMID- 19588192
TI  - Managing for multiple resources under climate change: national forests.
AB  - This study explores potential adaptation approaches in planning and management
      that the United States Forest Service might adopt to help achieve its goals and
      objectives in the face of climate change. Availability of information,
      vulnerability of ecological and socio-economic systems, and uncertainties
      associated with climate change, as well as the interacting non-climatic changes,
      influence selection of the adaptation approach. Resource assessments are
      opportunities to develop strategic information that could be used to identify and
      link adaptation strategies across planning levels. Within a National Forest,
      planning must incorporate the opportunity to identify vulnerabilities to climate
      change as well as incorporate approaches that allow management adjustments as the
      effects of climate change become apparent. The nature of environmental
      variability, the inevitability of novelty and surprise, and the range of
      management objectives and situations across the National Forest System implies
      that no single approach will fit all situations. A toolbox of management options
      would include practices focused on forestalling climate change effects by
      building resistance and resilience into current ecosystems, and on managing for
      change by enabling plants, animals, and ecosystems to adapt to climate change.
      Better and more widespread implementation of already known practices that reduce
      the impact of existing stressors represents an important "no regrets" strategy.
      These management opportunities will require agency consideration of its adaptive
      capacity, and ways to overcome potential barriers to these adaptation options.

PMID- 19588193
TI  - Recanalization of splenic artery aneurysm after transcatheter arterial
      embolization using N-butyl cyanoacrylate.
AB  - A 65-year-old woman who had been diagnosed as having microscopic polyangiitis
      developed sudden abdominal pain and entered a state of shock. Abdominal CT showed
      massive hemoperitoneum, and emergent angiography revealed a ruptured splenic
      artery aneurysm. After direct catheterization attempts failed due to tortuous
      vessels and angiospasm, transcatheter arterial embolization using an n-butyl
      cyanoacrylate (NBCA)-lipiodol mixture was successfully performed. Fifty days
      later, the patient developed sudden abdominal pain again. Repeated angiography
      demonstrated recanalization of the splenic artery and splenic artery aneurysm.
      This time, the recanalized aneurysm was embolized using metallic coils with the
      isolation method. Physicians should keep in mind that recanalization can occur
      after transcatheter arterial embolization using N-butyl cyanoacrylate, which has
      been used as a permanent embolic agent.

PMID- 19588194
TI  - Screening and identification of new isolate: thermostable Escherichia coli with
      novel thermoalkalotolerant cellulases.
AB  - A cellulase-producing bacterium strain was isolated from soil that produced novel
      thermoalkalotolerant cellulases after growth on CMC-Na agar screening plate at 37
      degrees C. It was identified as Escherichia coli using the method of 16S rRNA and
      intergenic spacer gene analysis combined with morphological, physiological, and
      biochemical tests. Three major components of the cellulases [carboxymethyl
      cellulase (CMCase), filter paper cellulase, and beta-glucosidase] were produced
      with maximal activities (0.23, 0.08, and 0.15 U/ml) and maximum specific
      activities 4.13, 0.56, and 0.50 U/mg protein after 72, 96, and 120 h growth,
      respectively. Maximum CMCase activity was measured at 50 degrees C and pH 6.0,
      respectively, and it also retained more than 60% of its maximal activity for at
      least 20 min at 50-70 degrees C and 10 min at 80 degrees C, respectively, and
      retained approximately 50% of its maximal activity after incubating at 90 degrees
      C for 10 min. The enzyme could be applied in bioconversion of lignocellulosic
      agricultural wastes.

PMID- 19588195
TI  - Typing of staphylococcal cassette chromosome mec encoding methicillin resistance
      in Staphylococcus aureus strains isolated at the bone marrow transplant centre of
      Tunisia.
AB  - Staphylococcal Cassette Chromosome mec (SCCmec) is a mobile genetic element that
      carries the gene mecA mediating the methicillin resistance in staphylococci. It
      is composed of mec and ccr gene complexes. Six SCCmec types have been defined so
      far. SCCmec typing of 13 methicillin-resistant Staphylococcus aureus (MRSA) out
      of 72 (18%) non redundant S. aureus strains recovered in 1998-2007 at the Bone
      Marrow Transplant Centre of Tunis was carried out. The isolates were identified
      by conventional methods. Antibiotic susceptibility was determined by oxacillin
      and cefoxitin disks and oxacillin MIC by E-test. Methicillin resistance was
      detected by mecA PCR. The SCCmec complex types were determined by PCR. The
      epidemiology of MRSA has been investigated by PFGE. Among 13 mecA positive
      strains, 12 were resistant to oxacillin (MIC = 3 to >256 microg/microl) and to
      cefoxitin and one strain was pre-resistant: susceptible to oxacillin (MIC = 0.19
      microg/microl) and to cefoxitin. Hospital-acquired MRSA (HA-MRSA) strains had
      essentially SCCmec type IV (nine strains) or III (two strains) or I (one strain).
      One strain shown to carry ccrAB1 and ccrAB2 genes in combination with class B
      mec. Seven of 13 MRSA strains isolated from 2000 to 2006 were classified with
      major similarity group A harbored SCCmec type IV.

PMID- 19588196
TI  - Virtual organization of hospital medical imaging: a user satisfaction survey.
AB  - A virtual medical imaging department is an innovative and demanding
      organizational model, to the extent that the underlying goal is to achieve a
      continuous and advanced organizational integration of human and physical
      resources, clinical data, and clienteles. To better understand the kind of
      benefits offered, we conducted a survey of three groups of users--radiologists,
      radiological technologists, and medical specialists--working in a five-site
      virtual organization. We received 127 valid questionnaires, for an overall
      response rate of 66%. The assessments vary according to the use made of the
      system. The scores for system quality and the quality of the data produced were
      markedly higher for intra-hospital use (respectively 7.9 and 8.7 out of 10) than
      for inter-hospital use (5.4 and 7.0). Despite the negative assessments they made
      of inter-hospital use, users maintained a positive attitude toward some type of
      virtual organization of medical imaging. Indeed, the score for Overall
      satisfaction with the system was very high, 8.9 out of 10. Moreover, the scores
      for Intended future use of the system were very high for both intra-hospital use
      (8.9) and inter-hospital use (8.7). We also found significant differences in
      perceptions among user groups.

PMID- 19588197
TI  - Synergistic interactions between Cry1Ac and natural cotton defenses limit
      survival of Cry1Ac-resistant Helicoverpa zea (Lepidoptera: Noctuidae) on Bt
      cotton.
AB  - Larvae of the bollworm Helicoverpa zea (Boddie) show some tolerance to Bacillus
      thuringiensis (Bt) Cry1Ac, and can survive on Cry1Ac-expressing Bt cotton, which
      should increase resistance development concerns. However, field-evolved
      resistance has not yet been observed. In a previous study, a population of H. zea
      was selected for stable resistance to Cry1Ac toxin. In the present study, we
      determined in laboratory bioassays if larvae of the Cry1Ac toxin-resistant H. zea
      population show higher survival rates on field-cultivated Bt cotton squares (=
      flower buds) collected prebloom-bloom than susceptible H. zea. Our results show
      that Cry1Ac toxin-resistant H. zea cannot complete larval development on Cry1Ac
      expressing Bt cotton, despite being more than 150-fold resistant to Cry1Ac toxin
      and able to survive until pupation on Cry1Ac toxin concentrations greater than
      present in Bt cotton squares. Since mortality observed for Cry1Ac-resistant H.
      zea on Bt cotton was higher than expected, we investigated whether Cry1Ac
      interacts with gossypol and or other compounds offered with cotton powder in
      artificial diet. Diet incorporation bioassays were conducted with Cry1Ac toxin
      alone, and with gossypol and 4% cotton powder in the presence and absence of
      Cry1Ac. Cry1Ac toxin was significantly more lethal to susceptible H. zea than to
      resistant H. zea, but no difference in susceptibility to gossypol was observed
      between strains. However, combinations of Cry1Ac with gossypol or cotton powder
      were synergistic against resistant, but not against susceptible H. zea. Gossypol
      concentrations in individual larvae showed no significant differences between
      insect strains, or between larvae fed gossypol alone vs. those fed gossypol plus
      Cry1Ac. These results may help explain the inability of Cry1Ac-resistant H. zea
      to complete development on Bt cotton, and the absence of field-evolved resistance
      to Bt cotton by this pest.

PMID- 19588198
TI  - Oxidative responses of St. Augustinegrasses to feeding of southern chinch bug,
      Blissus insularis Barber.
AB  - Southern chinch bug, Blissus insularis Barber (Hemiptera: Blissidae), is a
      serious insect pest of St. Augustinegrass, Stenotaphrum secundatum (Walt.)
      Kuntze, a turfgrass commonly grown in the southeastern United States. Resistance
      to southern chinch bug has been identified in the polyploid St. Augustinegrass
      varieties 'Floratam' and 'FX-10', and the diploid 'Captiva'. However, southern
      chinch bug in Florida and elsewhere has overcome Floratam's resistance. This
      research investigated the potential role of selected plant oxidative enzymes in
      resistance/susceptibility to southern chinch bug in two polyploid varieties (FX
      10 and Floratam) and two diploid varieties (Captiva and Palmetto). Oxidative
      enzyme activity was estimated spectrophotometrically from plant samples collected
      1, 3, 5, and 8 days after southern chinch bug infestation and from uninfested
      control plants. Resistant FX-10 and Captiva had significantly higher peroxidase
      activity, while Captiva had significantly higher polyphenol oxidase activity 5
      and 8 days after infestation compared to uninfested controls. FX-10 had higher
      lipoxygenase activity 3, 5, and 8 days after infestation compared to uninfested
      controls. Catalase activities did not differ between infested and control plants
      in any of the varieties tested. Native gels stained for peroxidase indicated that
      certain isozymes in FX-10 and Captiva were induced 5 and 8 days after
      infestation. Isozyme profiles of polyphenol oxidase and lipoxygenase did not
      differ between control and infested FX-10, Floratam, Captiva, and Palmetto.
      Potential mechanisms to explain the correlation of resistance to southern chinch
      bug in FX-10 and Captiva with higher activities of oxidative enzymes are
      discussed.

PMID- 19588199
TI  - Mate finding in the parasitic wasp Cephalonomia tarsalis (Ashmead): more than one
      way to a female's heart.
AB  - The parasitic wasp, Cephalonomia tarsalis (Hymenoptera: Bethylidae), parasitizes
      larvae of the sawtoothed grain beetle, Oryzaephilus surinamensis (L.)
      (Coleoptera: Silvanidae), and is used for biological control of this worldwide
      pest of stored grain. To study the hypothesis that C. tarsalis not only mates at
      its natal patch but also uses olfactory cues to find mating partners elsewhere,
      we investigated semiochemical use by male C. tarsalis. Olfactometer experiments
      revealed that male C. tarsalis are arrested by odors emanating from the cocoons
      of conspecifics, from young unmated females, and from feces of the host.
      Dodecanal, which was identified from extracts of filter paper contaminated by
      young females, had an arresting effect on males but not on females and was,
      therefore, considered as a sex pheromone. These findings indicate that C.
      tarsalis is a species with partial local mate competition. Males mate with
      females: 1) at the emergence site following location of females by sex pheromones
      from their cocoons, and 2) after dispersal from the natal patch following
      location of females directly by dodecanal and indirectly by unidentified sexual
      kairomones from host feces.

PMID- 19588201
TI  - Clinical significance of axillary microresiduals after neoadjuvant chemotherapy
      in breast cancer patients with cytologically proven metastases.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) has been widely accepted for advanced
      breast cancer patients, and pathological complete remission (pCR) was revealed to
      be an important prognostic factor. The pCR status of cytologically proven
      axillary metastases (ALN-pCR) offers a more powerful prognostic predictor than
      pCR of the main tumor. This study evaluated the clinical significance of residual
      micrometastases and discusses screening methods after NAC in patients with
      cytologically proven axillary metastases. METHODS: Eighty patients with a
      diagnosis of cytologically proven axillary metastases received NAC. All dissected
      lymph nodes were evaluated using multislice sectioning and cytokeratin
      immunohistochemistry, and categorized into four groups: no metastases (ALN-pCR),
      and with metastases <or=0.2 mm (ALN-itc), >0.2 mm but <or=2 mm (ALN-mic), and >2
      mm (ALN-mac). Disease-free survival (DFS) and overall survival (OS) were
      calculated by Kaplan-Meier method based on the status of residual metastases.
      RESULTS: DFS in patients with ALN-pCR and ALN-itc was significantly longer than
      that with ALN-mic (P = 0.007, P = 0.045, respectively). OS with ALN-pCR was
      significantly longer than that with ALN-mic (P = 0.004). There was no significant
      difference in DFS or OS between ALN-mac and ALN-mic. These data showed the
      clinical significance of microresidual metastases >0.2 mm after NAC in patients
      with cytologically proven axillary metastases. CONCLUSIONS: Using multislice
      sectioning, screening for ALN-mic after NAC was clinically important, and that
      for ALN-itc was not clinically essential.

PMID- 19588203
TI  - The contoured staged marginal and central surgical excision technique with en
      face histopathological analysis: useful additions in the armamentarium for
      treating and diagnosing melanoma in situ.

PMID- 19588200
TI  - Stigmasterol and cholesterol regulate the expression of elicitin genes in
      Phytophthora sojae.
AB  - Sterol acquisition by soilborne plant pathogens of the genus Phytophthora is
      presumed to involve extracellular proteins belonging to class-I elicitins.
      However, little is known about the relationship between sterol availability and
      elicitin secretion. The objective of this study was to determine the expression
      of class-I elicitin genes in Phytophthora sojae when grown in a medium containing
      stigmasterol or cholesterol. P. sojae growth was stimulated by nanomolar
      concentrations of stigmasterol and cholesterol, which also resulted in the down
      regulation of its elicitin genes over time when expression profiles were
      monitored using real time Reverse Transcription Polymerase Chain Reaction (RT
      PCR). The down-regulation of elicitin genes in response to the two sterols also
      coincided with a reduction in the amount of elicitins detected in spent
      filtrates. Our study is the first to show the influence of sterols on elicitin
      gene expression in Phytophthora, which is important with respect to the ecology
      of elicitin secretion as sterol carrier proteins in the environment.

PMID- 19588204
TI  - Hepatic stellate cells promote liver metastasis of colon cancer cells by the
      action of SDF-1/CXCR4 axis.
AB  - BACKGROUND: It has been determined that the chemokine receptor CXCR4 and its
      ligand stromal cell-derived factor-1 (SDF-1) regulate several key processes in a
      wide variety of cancers. However, the function and mechanism of the SDF-1/CXCR4
      system in the metastasis of colorectal cancer remain controversial. METHODS:
      Immunohistochemistry was performed to examine quantitatively the expression of
      CXCR4 in 40 human samples of colorectal cancer and liver metastasis. The
      functions of SDF-1 on HCT116 colon cancer cells were investigated in vitro. We
      subcutaneously inoculated HCT116 cells with hepatic stellate cells (HSCs)
      expressing SDF-1. The CXCR4 inhibitor AMD3100 was tested in vitro and in vivo.
      RESULTS: By quantitatively counting the number of cells, it was shown that there
      are more CXCR4-positive cells at the metastatic site in the liver compared with
      the primary sites. We demonstrated the effect of SDF-1 on the invasion and
      antiapoptosis of HCT116 cells in vitro. In mouse experiment of liver metastasis,
      intraperitoneal administration of AMD3100 blocked the metastatic potential of
      HCT116 cells. Furthermore, we found that alpha-smooth muscle actin (alpha-SMA)
      positive myofibroblasts derived from HSCs, surrounding the liver metastasis foci,
      secreted SDF-1. The subcutaneous inoculation of HCT116 cells with HSCs promoted
      the tumor initiation in nude mice, indicating the importance of the direct
      interaction between these cells in vivo. CONCLUSION: These results suggest that
      HSCs play important role in liver metastasis of colon cancer cells by the action
      of SDF-1/CXCR4 axis and provide preclinical evidence that blockade of the axis is
      a target for antimetastasis therapy.

PMID- 19588207
TI  - Neurochemical oscillations in the basal ganglia.
AB  - This work represents an attempt to elucidate the neurochemical processes in the
      basal ganglia by mathematical modelling. The correlation between neurochemistry
      and electrophysiology has been used to construct a dynamical system based on the
      basal ganglia's network structure. Mathematical models were constructed for
      different physical scales to reformulate the neurochemical and
      electrophysiological behaviour from synapses up to multi-compartment systems.
      Transformation functions have been developed to transit between the different
      scales. We show through numerical simulations that this network produces
      oscillations in the electrical potentials as well as in neurotransmitter
      concentrations. In agreement with pharmacological experiments, a parameter
      sensitivity analysis reveals temporary changes in the neurochemical and
      electrophysiological systems after single exposure to antipsychotic drugs. This
      behaviour states the structural stability of the system. The correlation between
      the neurochemical dynamics and drug-induced behaviour provides the perspective
      for novel neurobiological hypotheses.

PMID- 19588206
TI  - The use of F-18 choline PET in the assessment of bone metastases in prostate
      cancer: correlation with morphological changes on CT.
AB  - AIM: F-18 fluor choline-positron emission tomography/computed tomography (FCH
      PET/CT) has emerged as a new diagnostic tool for the imaging of prostate cancer.
      In this study, we have evaluated the potential role of FCH-PET/CT for the
      assessment of bone metastases in patients with prostate cancer. Furthermore, we
      assessed the pattern of metabolic uptake by FCH in relation to morphologic
      changes on CT. METHODS: Seventy men with biopsy-proven prostate cancer underwent
      FCH-PET/CT for preoperative staging or follow-up evaluation. Thirty-two patients
      were evaluated preoperatively, and 38 patients were referred for postoperative
      evaluation of suspected recurrence or progression based on clinical algorithms.
      PET imaging consisted of a dynamic PET/CT acquisition of the pelvic region during
      8 min (1 min frames) starting 1 min after i.v. injection of 4.07 MBq/kg/bw FCH,
      which was followed immediately by a semi-whole body acquisition. RESULTS:
      Overall, 262 lesions showed increased uptake on FCH-PET. Two hundred ten lesions
      (210 of 262) were interpreted as bone metastases. The mean of maximum
      standardized uptake value (SUV(max)) in all malignant lesions was 8.1 +/- 3.9.
      Forty-nine lesions (24%) had no detectable morphological changes on CT-probably
      due to bone marrow metastases. Fifty-six sclerotic lesions (having a Hounsfield
      unit (HU) level of more than 825) were interpreted as highly suspicious for
      metastatic bone disease on CT and/or other imaging modalities such as the bone
      scan, but showed no FCH uptake. There was a significant correlation between
      tracer uptake as assessed by SUV and the density of sclerotic lesions by HU (r = 
      0.52, p < 0.001). The sensitivity, specificity, and accuracy of FCH-PET/CT in
      detecting bone metastases from prostate cancer was 79%, 97%, and 84%,
      respectively. CONCLUSION: FCH-PET/CT showed promising results for the early
      detection of bone metastases in prostate cancer patients. We have found that a HU
      level of above 825 is associated with an absence of FCH uptake. Almost all of the
      FCH-negative sclerotic lesions were detected in patients who were under hormone
      therapy, which raises the possibility that these lesions might no longer be
      viable. However, clarification and the prognostic value of such lesions require
      further research.

PMID- 19588208
TI  - Agreement between Initial Classification and Subsequent Reclassification of
      Fractures of the Distal Radius in a Prospective Cohort Study.
AB  - We tested the hypothesis that the original surgeon-investigator classification of
      a fracture of the distal radius in a prospective cohort study would have moderate
      agreement with the final classification by the team performing final analysis of
      the data. The initial post-injury radiographs of 621 patients with distal radius
      fractures from a multicenter international prospective cohort study were
      classified according to the Comprehensive Classification of Fractures, first by
      the treating surgeon-investigator and then by a research team analyzing the data.
      Correspondence between original and revised classification was evaluated using
      the Kappa statistic at the type, group and subgroup levels. The agreement between
      initial and revised classifications decreased from Type (moderate; Kappa(type) =
      0.60), to Group (moderate; Kappa(group) = 0.41), to Subgroup (fair;
      Kappa(subgroup) = 0.33) classifications (all p < 0.05). There was only moderate
      agreement in the classification of fractures of the distal radius between surgeon
      investigators and final evaluators in a prospective multicenter cohort study.
      Such variations might influence interpretation and comparability of the data. The
      lack of a reference standard for classification complicates efforts to lessen
      variability and improve consensus.

PMID- 19588205
TI  - Inhibition of phosphatidylinositol 3-kinase/Akt signaling suppresses tumor cell
      proliferation and neuroendocrine marker expression in GI carcinoid tumors.
AB  - BACKGROUND: Overactivation of PI3K/Akt signaling facilitates tumor proliferation
      in several cancers. We have shown that various signal transduction pathways
      promote tumorigenesis in carcinoid tumors, which exhibit endogenously high levels
      of active, phosphorylated Akt. Therefore, we hypothesized that inhibition of the
      PI3K/Akt pathway would suppress carcinoid tumor cell growth and neuroendocrine
      (NE) marker production. METHODS: Human carcinoid BON cells were treated in vitro
      with LY294002, a PI3-kinase inhibitor, or transfected with Akt1 siRNA. Tumor cell
      proliferation was measured by MTT for 6 days. The effect of LY294002 or Akt1
      siRNA treatment was assessed by Western analysis. We examined the levels of
      phosphorylated Akt, total Akt, Akt1, and the NE markers human achaete-scute
      homolog1 (ASCL1) and chromogranin A (CgA). RESULTS: Treatment of BON cells with
      LY294002 reduced tumor cell proliferation (76%) in a dose-dependent manner.
      Growth also decreased in Akt1 siRNA transfected cells (26%). Levels of active,
      phosphorylated Akt and the NE tumor markers, ASCL1 and CgA, were diminished with
      both LY294002 and Akt1 siRNA treatments proportional to the degree of Akt
      inhibition. Total Akt, Akt2, and Akt3 levels were unaffected by these
      experiments. CONCLUSIONS: These data indicate that PI3K/Akt signaling performs a
      critical role in human carcinoid tumor cell survival and NE hormone generation.
      Furthermore, the development of novel therapeutics targeting Akt1 or components
      of the PI3K/Akt pathway may enhance the management of carcinoid disease.

PMID- 19588209
TI  - Case report: Longitudinal stress fracture of the humerus: imaging features and
      pitfalls.
AB  - Longitudinal stress fractures are an uncommon injury in which a diaphyseal
      fracture line occurs parallel to the long axis of a bone in the absence of direct
      trauma. They have been described in the tibia and less commonly in the femur but
      apparently not in the upper limb. We report a longitudinal stress fracture
      occurring in the humerus of a 62-year-old woman who had a history of osteoporosis
      and had undergone recent surgery of the contralateral wrist. We present the
      radiographic, MRI, and CT features of the case and emphasize the difficulties in
      diagnosis caused by negative findings on early radiographs and by nonspecific
      bone marrow edema pattern on MRI. The risk of a contralateral upper extremity
      stress fracture from activities of daily living in a patient with osteoporosis
      whose other upper extremity is immobilized also is highlighted.

PMID- 19588210
TI  - Acetabular retroversion in military recruits with femoral neck stress fractures.
AB  - Acetabular retroversion (AR) alters load distribution across the hip and is more
      prevalent in pathologic conditions involving the hip. We hypothesized the
      abnormal orientation and mechanical changes may predispose certain individuals to
      stress injuries of the femoral neck. We retrospectively reviewed the
      anteroposterior (AP) pelvic radiographs of 54 patients (108 hips) treated for a
      femoral neck stress fracture (FNSF) and compared these radiographs with those for
      a control group of patients with normal pelvic radiographs. We determined
      presence of a crossover sign (COS), femoral neck abnormalities, and neck shaft
      angle. The prevalence of a positive COS was greater in patients with stress
      fractures than in the control subjects (31 of 54 [57%] versus 17 of 54 [31%],
      respectively) and higher than for control subjects reported in the literature.
      Thirteen patients had radiographic changes of the femoral neck consistent with
      femoroacetabular impingement (FAI). These radiographic abnormalities were seen
      more commonly in retroverted hips. A greater incidence of AR was noted in
      patients with FNSF. Potential implications include more aggressive screening of
      military recruits with AR and the new onset of hip pain. Finally, we present an
      algorithm we use to diagnose and treat these relatively rare FNSFs. LEVEL OF
      EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19588211
TI  - Enhancement of difficult nonunion in children with osteogenic protein-1 (OP-1):
      early experience.
AB  - Numerous studies have described the use of osteogenic protein-1 (OP-1) in adults,
      but there are few reports in children. The objectives of this short-term followup
      cohort study were (1) to examine clinical and radiographic healing of persistent
      nonunions after OP-1 application in children; and (2) to determine the safety of
      OP-1 use in this sample. Clinical healing was defined by absence of pain and
      tenderness at the nonunion site and the ability to fully weight bear on the
      affected limb. Radiographic healing was determined by bony bridging of the
      nonunion site in at least one view. Safety was defined as the absence of major
      adverse events, including allergic reactions, infections, local inflammatory
      reactions, and heterotopic ossification. OP-1 was used in 19 patients who had an
      operative procedure for the bridging of persistent nonunions between 1999 and
      2007. The mean age was 11.6 years (range, 4.8-20.3 years). Thirteen patients had
      persistent nonunion after one or more previous surgeries, prior to the initial OP
      1 application. A single dose of 3.5 mg of OP-1 mixed with 1 g of Type I bovine
      collagen was applied to 23 sites of 19 patients. Three patients received
      additional OP-1 applications. Healing occurred clinically and radiographically in
      17 of the 23 sites. Complications included four superficial pin site infections,
      one deep infection, and two fractures. No major local adverse event related to OP
      1 application was noted in our sample. Our findings suggest OP-1 stimulates
      healing of persistent nonunions without major adverse events in our patient
      population. LEVEL OF EVIDENCE: Level IV, case series. See the guidelines online
      for a complete description of levels of evidence.

PMID- 19588212
TI  - Case reports: unusual cause of shoulder pain in a collegiate baseball player.
AB  - The objective of reporting this case was to introduce a unique cause of shoulder
      pain in a high-level Division I NCAA collegiate baseball player. Various
      neurovascular causes of shoulder pain have been described in the overhead
      athlete, including quadrilateral space syndrome, thoracic outlet syndrome, effort
      thrombosis, and suprascapular nerve entrapment. All of these syndromes are
      uncommon and frequently are missed as a result of their rarity and the need for
      specialized tests to confirm the diagnosis. This pitcher presented with
      nonspecific posterior shoulder pain that was so severe he could not throw more
      than 50 feet. Eventually, intermittent axillary artery compression with the arm
      in abduction resulting from hypertrophy of the pectoralis minor and scalene
      muscles was documented by performing arteriography with the arm in 120 degrees
      abduction. MRI-MR angiographic evaluation revealed no anatomic abnormalities. The
      patient was treated successfully with a nonoperative rehabilitation program and
      after 6 months was able to successfully compete at the same level without pain.

PMID- 19588213
TI  - Does myocardial perfusion scintigraphy predict improvement in symptoms and
      exercise capacity following successful elective percutaneous coronary
      intervention?
AB  - BACKGROUND: Elective percutaneous coronary intervention (PCI) without inducible
      ischaemia may not be beneficial. We investigated the prevalence of inducible
      hypoperfusion using myocardial perfusion scintigraphy (MPS) in patients
      undergoing PCI, and its ability to predict functional outcome. METHODS AND
      RESULTS: One hundred and twenty-three patients listed for elective PCI underwent
      MPS, using treadmill exercise where possible. Seventy-seven patients (63%)
      described chest pain in daily life. Seventy-four of 103 (72%) exercise ECG tests
      were positive. Ninety-one (74%) had inducible hypoperfusion on MPS (extensive in
      25; 20%). Interventionalists were blinded to the scintigraphic results, and PCI
      was performed as planned. Six months later, Seattle Angina Questionnaire physical
      limitation score had improved from 66 to 76 (P < 0.0001), and peak treadmill
      workload from 7.2 +/- 2.3 to 9.0 +/- 2.7 METS (P < 0.0001). Sex, limiting chest
      pain on baseline exercise testing, and MPS summed difference score (SDS) were
      independent predictors of improvement. Patients with both limiting chest pain and
      SDS > or = 7 demonstrated an increase of 3.3 +/- 1.8 METS, compared with
      approximately 1.5 METS for other subgroups (P < 0.05). CONCLUSIONS: Many patients
      undergoing elective PCI in a UK centre have little or no evidence of inducible
      hypoperfusion. The combination of limiting chest pain during exercise testing and
      significant inducible hypoperfusion on MPS predicts a large increase in exercise
      capacity after PCI.

PMID- 19588215
TI  - How long the lymphoscintigraphy imaging should be continued for sentinel lymph
      node mapping?
AB  - OBJECTIVE: We assessed the need for delayed lymphoscintigraphy imaging for
      sentinel lymph node (SLN) biopsy in stage I and II breast cancer patients using
      intradermal injection of (99m)Tc-antimony sulfide colloid. METHOD: Seventy-five
      patients with early-stage breast cancer were included in our study. Periareolar
      intradermal injections of 0.5 mCi/0.2 mL (99m)Tc-antimony sulfide colloid was
      used for the patients without previous excisional biopsy (45 patients). Two
      intradermal injection of 0.5 mCi/0.2 mL (99m)Tc-antimony sulfide colloid was used
      on each side of the dermal incision in patients with the history of excisional
      biopsy (30 patients). Anterior and lateral static images were taken at 2 min. If
      SLN was not visualized, delayed imaging at 5, 10, 30, 60, 90, 150, and 180 min
      was done (till the visualization of the SLN or 180 min). SLN was performed by the
      combination of gamma probe and blue dye during surgery. RESULTS: Sentinel lymph
      node detection rate was 96% (72/75). SLNs were detected on the immediate (2 min)
      images in 55 (73.33%) patients. In the remaining patients, the SLNs were detected
      first on the 5-, 10-, and 30-min images in 10 (13/33%), 5 (6.66%), and 2 (2.66%)
      patients, respectively. In three patients (4%), SLN was not detected by
      lymphoscintigraphy even on 180-min images. During surgery, SLN was not detected
      in these three patients either. CONCLUSION: Considering the rapid flow of (99m)Tc
      antimony sulfide colloid in our study, lymphoscintigraphy imaging can be
      completed in the nuclear medicine department without any delay in sending the
      patient back to the surgery department. Thirty minutes after radiotracer
      injection seems to be the optimal time for lymphoscintigraphy and delayed imaging
      beyond 30 min would not be necessary.

PMID- 19588214
TI  - Injectable hydrogels providing sustained delivery of vascular endothelial growth
      factor are neuroprotective in a rat model of Huntington's disease.
AB  - Vascular endothelial growth factor (VEGF) is a potent peptide with well
      documented pro-angiogenic effects. Recently, it has also become clear that
      exogenous administration of VEGF is neuroprotective in animal models of central
      nervous system diseases. In the present study, VEGF was incorporated into a
      sustained release hydrogel delivery system to examine its potential benefits in a
      rat model of Huntington's disease (HD). The VEGF-containing hydrogel was
      stereotaxically injected into the striatum of adult rats. Three days later,
      quinolinic acid (QA; 225 nmol) was injected into the ipsilateral striatum to
      produce neuronal loss and behavioral deficits that mimic those observed in HD.
      Two weeks after surgery, animals were tested for motor function using the
      placement and cylinder tests. Control animals received either QA alone or QA plus
      empty hydrogel implants. Behavioral testing confirmed that the QA lesion resulted
      in significant deficits in the ability of the control animals to use their
      contralateral forelimb. In contrast, the performance of those animals receiving
      VEGF was significantly improved relative to controls with only modest motor
      impairments observed. Stereological counts of NeuN-positive neurons throughout
      the striatum demonstrated that VEGF implants significantly protected against the
      loss of striatal neurons induced by QA. These data are the first to demonstrate
      that VEGF can be used to protect striatal neurons from excitotoxic damage in a
      rat model of HD.

PMID- 19588216
TI  - Effect of respiratory motion on quantitative myocardial gated SPECT: a simulation
      study.
AB  - OBJECTIVE: Respiratory motion is a potential cause of artefact and downgrading
      the quality of ECG-gated single photon emission computed tomography (SPECT)
      images that may result in clinical misinterpretation. We studied qualitatively
      the effects of respiratory motion on gated SPECT myocardial perfusion and
      function using Monte Carlo simulated data. METHODS: NCAT phantom was used to
      model a human torso. The cardiac and respiratory cycles of torso were 1 and 5 s,
      respectively. Eight realizations of the phantom, having diaphragmatic motion
      amplitudes of 0-7 cm were generated. SimSET Monte Carol simulator was used to
      image the phantom and generate gated studies of 16 frames per cardiac cycle.
      RESULTS: Our results demonstrated the underestimation of left ventricle end
      diastolic, end-systolic, stroke volumes and ejection fraction and overestimation
      of wall motion and wall thickening (p < 0.01). In addition, the mean percentage
      of count in the basal-inferior, mid-inferior, apical-inferior, basal-septal and
      mid-septal segments were significantly lower due to respiratory motion when
      compared with control (p < 0.01). The changes in uptake were not significant in
      the apex, antroapical, apicoseptal, apicolateral, mid-anterior, basal-anterior,
      mid-lateral and basal-lateral segments. CONCLUSION: Respiratory motion has
      significant effect on the calculation of the left ventricular functional and
      regional myocardial perfusion in the GSPECT. The amount of deterioration and
      quality distortion of the images depends on the amplitude of the diaphragmatic
      motion.

PMID- 19588217
TI  - Chronic inflammatory demyelinating polyneuropathy accompanied by chronic
      myelomonocytic leukemia: possible pathogenesis of autoimmunity in myelodysplastic
      syndrome.
AB  - Paraneoplastic neuropathies have rarely been reported in patients with
      hematological malignancies. We report herein the case of a 65-year-old Japanese
      woman with chronic myelomonocytic leukemia (CMML) accompanying chronic
      inflammatory demyelinating polyneuropathy (CIDP). She had been diagnosed with
      refractory anemia and subsequently developed CMML with cytogenetic abnormalities
      including t(3;8)(q26;q24). While regenerating bone marrow following induction
      chemotherapy, she complained of numbness in the lower legs and then became unable
      to walk. Clinical and electrophysiological features were consistent with CIDP.
      Intravenous immunoglobulin treatment was insufficient, although corticosteroids
      reduced neurological symptoms. This case suggests CIDP as one of the autoimmune
      phenomena associated with myelodysplastic syndrome and immunosuppressive
      treatment represents an effective therapy.

PMID- 19588218
TI  - Superwarfarin intoxication: hematuria is a major clinical manifestation.
AB  - Since superwarfarin is popular and readily available in stores, it may cause
      intoxication or overexposure, which can result in coagulopathy or abnormal
      bleeding in humans and, thus, is an important public health problem. We report
      our clinical experience with superwarfarin intoxication. Nine patients, including
      eight patients who had histories of ingesting superwarfarin, were studied. Of the
      patients, hematuria occurred in eight. Laboratory tests among the nine patients
      showed extremely prolonged prothrombin times and activated partial thromboplastin
      times, which could be corrected to normal by mixing 1:1 with normal pooled
      plasma; they also had very low functional levels of factor II, VII, IX, X, and
      proteins C and S, but normal functional levels of factors V, VIII, fibrinogen,
      and anti-thrombin III. Large doses of vitamin K1 were needed for 3 months or more
      to treat and correct the coagulopathy among the patients. The majority of the
      patients presented with gross hematuria, suggesting that hematuria is probably a
      major clinical manifestation of superwarfarin intoxication. Prolonged use of
      large doses of vitamin K1 is needed for the treatment of superwarfarin
      intoxication.

PMID- 19588219
TI  - M-protein-positive chronic active Epstein-Barr virus infection: features
      mimicking HIV-1 infection.
AB  - Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal
      lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE.
      The significance of such immunoglobulin abnormalities in CAEBV has not been fully
      evaluated and discussed. In addition, such clinical features mimic HIV-1
      infection. We report here a case of CAEBV with M-protein detected which may shed
      a new light on the pathogenesis of this disease.

PMID- 19588220
TI  - Composite gastrointestinal lymphoma consisting of diffuse large B-cell lymphoma
      and peripheral T-cell lymphoma.

PMID- 19588222
TI  - Molecular characterization of a new macluravirus from yam in Yunnan, China.

PMID- 19588223
TI  - Population-specific functional variant of the TPH2 gene 2755C>A polymorphism
      contributes risk association to major depression and anxiety in Chinese
      peripartum women.
AB  - The rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase 2
      (TPH2), is one of the most promising candidate genes for psychiatric disorders.
      Although evidence strongly suggests that the TPH2 is significant in the etiology
      of major depression and anxiety disorder, whether it also contributes to the
      etiology of peripartum major depression and anxiety disorder, a specific subtype
      influenced considerably by other environmental factors like hormones, is unclear.
      This study investigated the role of TPH2 in the etiology of peripartum major
      depression and anxiety disorder in a Han Chinese population in Taiwan. Six single
      nucleotide polymorphisms were selected from previously profiled genetic
      information of TPH2 in Han Chinese. A cohort of postpartum Chinese women that
      included 117 patients with major depression, anxiety disorder, or both and 83
      healthy controls were genotyped with selected TPH2 markers. The TPH2 2755A allele
      was found only in women with peripartum major depression and anxiety disorder (p
      = 0.043) and exhibited a dominant gene action (p = 0.038) with an estimated
      disease risk of 1.73. Although the sample size is small, results from this study
      suggest that the TPH2 C2755A polymorphism may represent a population-specific
      risk factor for peripartum major depression and anxiety disorder, perhaps by
      interacting with hormones.

PMID- 19588221
TI  - Effect of high frequency repetitive transcranial magnetic stimulation on reaction
      time, clinical features and cognitive functions in patients with Parkinson's
      disease.
AB  - The aim of the present study was to investigate the effects of one session of
      high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over
      the left dorsal premotor cortex (PMd) and left dorsolateral prefrontal cortex
      (DLPFC) on choice reaction time in a noise-compatibility task, and cognitive
      functions in patients with Parkinson's disease (PD). Clinical motor symptoms of
      PD were assessed as well. Ten patients with PD entered a randomized, placebo
      controlled study with a crossover design. Each patient received 10 Hz stimulation
      over the left PMd and DLPFC (active stimulation sites) and the occipital cortex
      (OCC; a control stimulation site) in the OFF motor state, i.e. at least after 12
      h of dopaminergic drugs withdrawal. Frameless stereotaxy was used to target the
      optimal position of the coil. For the evaluation of reaction time, we used a
      noise-compatibility paradigm. A short battery of neuropsychological tests was
      performed to evaluate executive functions, working memory, and psychomotor speed.
      Clinical assessment included a clinical motor evaluation using part III of the
      Unified Parkinson's Disease Rating Scale. Statistical analysis revealed no
      significant effect of rTMS applied over the left PMd and/or DLPFC in patients
      with PD in any of the measured parameters. In this study, we did not observe any
      effect of one session of high frequency rTMS applied over the left PMd and/or
      DLPFC on choice reaction time in a noise-compatibility task, cognitive functions,
      or motor features in patients with PD. rTMS applied over all three stimulated
      areas was well tolerated and safe in terms of the cognitive and motor effects.

PMID- 19588224
TI  - It is never too late: a deceitful gastric ulcer.

PMID- 19588225
TI  - Thigh infection and subcutaneous emphysema: an emergency, review of literature
      and case discussion.
AB  - Thigh infection associated with local emphysematous signs on presentation to the
      emergency room should alert the medical staff at once of potential complication
      associated with it. The infection may be associated with underlying bowel
      pathology and has a high mortality rate. Hence, emergency treatment should be
      instituted. We discuss a case with this uncommon presentation, treatment
      administered and relevant literature.

PMID- 19588226
TI  - Intracystic papillary carcinoma of the male breast: a case report and review of
      the literature.
AB  - INTRODUCTION: Carcinoma of the male breast is an infrequent and poorly understood
      disease (Sinha et al. in Ann R Coll Surg Engl 88(5):W3-W5, 2006). It differs from
      female breast cancer in both demographic and histopathological characteristics.
      MATERIALS AND METHODS: Herein we describe a case of intracystic papillary
      carcinoma in situ in a male breast with a review of the literature. CONCLUSION:
      Although rare, in situ carcinoma constitutes a larger proportion of male than
      female breast cancer in a non-screened population. It is characteristically of
      the papillary and micropapillary subtype. Intracystic papillary carcinoma is a
      noncomedo intraductal carcinoma constituting about 0.5% of female breast cancers
      and is associated with a slightly inferior prognosis than other noncomedo
      intraductal carcinomas (Lefkowitz et al. in Hum Pathol 25:802-809, 1994).

PMID- 19588227
TI  - Management of primary intracranial germ cell tumors.
AB  - Primary intracranial germ cell tumors are rare and usually localized in the
      pineal and the suprasellar regions. They are divided into the following
      histologic types: germinoma, teratoma (mature, immature, malignant),
      choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor),
      and mixed tumors. Clinically, they are manifested with ocular signs or signs of
      obstructive hydrocephalus. Localized germinomas are treated with radiation
      therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for
      disseminated germinomas. Mature teratomas are treated with surgery. The rest of
      germ cell tumors are managed with various combinations of surgery, chemotherapy,
      and radiotherapy depending on the tumor type. If the tumors secrete beta-human
      chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can
      be used to accurately monitor response to treatment. Prognosis is best for
      germinomas and mature teratomas and worst for choriocarcinomas and embryonal
      carcinomas.

PMID- 19588228
TI  - Convection enhanced delivery of boronated EGF as a molecular targeting agent for
      neutron capture therapy of brain tumors.
AB  - In the present study, we have evaluated a boronated dendrimer-epidermal growth
      factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron
      capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma,
      designated F98(EGFR). EGF was chemically linked to a heavily boronated
      polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS.
      Biodistribution studies were carried out at 6 h and 24 h following intratumoral
      (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of
      (125)I-labeled or unlabeled BD-EGF (40 microg (10)B/10 microg EGF) to F98 glioma
      bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors
      following CED compared to i.t. injection, and a doubling of the tumor boron
      concentration (22.3 microg/g vs. 11.7 microg/g). CED of BD-EGF resulted in a 7.2x
      increase in the volume of distribution within the infused cerebral hemisphere and
      a 1.9x increase in tumor uptake of BD-EGF compared with i.t. injection. Based on
      these favorable biodistribution data, BNCT was carried out at the Massachusetts
      Institute of Technology nuclear reactor 14 days following i.c. tumor implantation
      and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 +/- 4.7 days
      compared to 43.0 +/- 2.8 days following i.t. injection. Rats that received BD-EGF
      by CED in combination with i.v. boronophenylalanine (BPA), which has been used in
      both experimental and clinical studies, had a MST of 86.0 +/- 28.1 days compared
      to 39.8 +/- 1.6 days for i.v. BPA alone (P < 0.01), 30.9 +/- 1.4 days for
      irradiated controls and 25.1 +/- 1.0 days for untreated controls (overall P <
      0.0001). These data have demonstrated that the efficacy of BNCT was significantly
      increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and
      that the survival data were equivalent to those previously reported by us using
      the boronated anti-human-EGF mAb, C225 (cetuximab).

PMID- 19588229
TI  - Alterations in peroxisome proliferator-activated receptor mRNA expression in
      skeletal muscle after acute and repeated bouts of exercise.
AB  - Peroxisome proliferator-activated receptors (PPAR) exist in three different
      forms, alpha (alpha), beta/delta (beta/delta), or gamma (gamma), all of which are
      expressed in skeletal muscle and play a critical role in the regulation of
      oxidative metabolism. The purpose of this investigation was to determine the mRNA
      expression pattern of the different PPARs and peroxisome proliferator-activated
      receptor alpha coactivator-1 alpha (PGC-1alpha) in muscles that largely rely on
      either glycolytic (plantaris) or oxidative (soleus) metabolism. Further, we also
      examined the alterations in the PPARs mRNA expression after one bout of endurance
      exercise or after 12 weeks of exercise training in the different muscles. Female
      Sprague-Dawley rats (5-8 months) were either run on the treadmill once or
      exercised trained for 12 weeks. The muscles were removed 24 h after the last bout
      of exercise. The results demonstrated with the exception of PPAR beta/delta, the
      PPAR mRNAs are expressed to a greater extent in the soleus muscle than in the
      plantaris muscle in sedentary animals. PPARgamma was the least abundantly
      expressed PPAR in either the soleus or the plantaris muscle. With respect to
      exercise training, only PPARgamma mRNA expression increased in the soleus muscle,
      while PPARbeta/delta and gamma mRNA levels increased in the plantaris muscle.
      Minimal changes were detected in any of the PPARs with one bout of exercise
      training. These results suggest that PPARgamma mRNA levels are the lowest in
      skeletal muscle among all of the PPARs and PPARgamma mRNA is the most responsive
      to changes in physical activity levels.

PMID- 19588230
TI  - HMGb1 promotes scratch wound closure of HaCaT keratinocytes via ERK1/2
      activation.
AB  - HMGb1 is a DNA-binding protein whose role as an extracellular cytokine in
      inflammation and tissue regeneration has also been reported. Given the importance
      of keratinocytes in wound healing, we have studied the mechanism of action of
      HMGb1 on HaCaT keratinocytes during in vitro scratch wound repair. Western blot
      and confocal immunofluorescence microscopy showed that these cells express
      significant amounts of HMGb1, that the protein is prevalently localized in the
      nucleus, and that its release by cells is negligible. Western blot also showed
      that these cells express the HMGb1 receptor RAGE. Cell exposure to HMGb1 in the
      absence of serum resulted in a stimulation of cell proliferation and ERK1/2
      activation. HMGb1 also accelerated the wound closure of scratch wounded cells and
      promoted cell migration, as evaluated by a transwell assay. The HMGb1-induced
      increases of cell proliferation, cell migration, and wound closure were abolished
      by the MEK inhibitor PD98059. Taken together, data show that, although HMGb1 is
      not released by HaCaT, when applied exogenously it can induce a marked increase
      of the wound repair of these cells. Data also suggest that HMGb1 acts via the
      RAGE/MEK/ERK pathway. These results bring scientific support to the potential
      application of HMGb1 in regenerative medicine.

PMID- 19588231
TI  - The enhancement of Raf-1 kinase activity by knockdown of Spry2 is associated with
      high sensitivity to paclitaxel in v-Ha-ras-transformed NIH 3T3 fibroblasts.
AB  - We previously demonstrated that the downregulation of Raf-1 kinase may contribute
      to the development of acquired resistance in paclitaxel-resistant cells. In this
      study, we determine whether the sensitivities of parental and its v-Ha-ras
      transformed NIH 3T3 cells to paclitaxel were dependent on Raf-1 kinase activity.
      Paclitaxel sensitivity of v-Ha-ras-transformed cells was found to be
      significantly higher than that of its parental cells. Paclitaxel transiently
      increased Raf-1 kinase activity in v-Ha-ras-transformed cells while showing no
      effect on its parental cells, suggesting that the Raf-1-MAP kinase pathway is
      proapoptotic. Furthermore, using siRNA-mediated Raf-1 knockdown analysis, we
      showed that Raf-1 knockdown cells were more resistant than control cells to
      paclitaxel treatment. In particular, the expression of the gene SPRY2, which has
      been known to act as an inhibitor on Ras/Raf/MAPK signaling, was downregulated
      after the treatment with paclitaxel. Methylation-specific PCR also revealed that
      downregulation of Spry2 was associated with altered methylation of the CpG-rich
      region of the SPRY2 exon 1. In addition, the Spry2 protein knockdown cells were
      more susceptible to paclitaxel treatment than control cells. Taken together, our
      results suggest that the enhancement of Raf-1 kinase activity by knockdown of
      Spry2 is associated with high sensitivity to paclitaxel.

PMID- 19588232
TI  - A mechanism of nucleocytoplasmic trafficking for the homeodomain protein PRH.
AB  - Proline-rich homeodomain (PRH)/hematopoietically expressed homeodomain (Hex) is a
      homeodomain protein that plays an important role in early embryonic patterning
      and hematopoiesis. PRH can act as either a tumor suppressor or an oncogene and
      its expression is dysregulated in certain types of lymphoid and myeloid
      leukemias. Aberrant exclusion of PRH from the nuclei has been associated with
      thyroid and breast cancers and a subset of myeloid leukemias. Accordingly,
      nuclear localization of PRH was found to be necessary for the inhibition of eIF4E
      dependent transformation. Since PRH's nuclear-cytoplasmic localization has been
      associated with neoplastic transformation we sought to better understand how PRH
      is transported to the nuclear compartment. Here, we report an essential element
      that controls the mechanism of PRH nucleocytoplasmic trafficking, namely that it
      is imported into the nuclei by Karyopherin/Importin 7. Kap7 was identified as a
      binding partner for PRH in a GST-pull down from a HeLa cell protein lysate,
      followed by mass-spectrometry. The Kap7-PRH complex is dissociated in the
      presence of RanGTP, as expected for a nuclear import complex. Kap7 can bind
      directly to PRH in a GST-pull down assay with purified proteins, as well as
      mediates the transport of PRH to the nuclear compartment in a digitonin
      permeabilized cells assay. Finally, in vivo depletion of Kap7 dramatically
      reduces accumulation of PRH in the nucleus. Our data open the way for
      investigations of the mechanism of perturbed PRH localization in tumors and
      possible therapeutic interventions.

PMID- 19588233
TI  - Physical and cytocompatibility properties of bioactive glass-polyvinyl alcohol
      sodium alginate biocomposite foams prepared via sol-gel processing for trabecular
      bone regeneration.
AB  - In the present work, biocomposite foams of bioactive glass along with polyvinyl
      alcohol and sodium alginate are designed and developed as a potential biomaterial
      for bone regeneration. These biocomposite foams have a low density of 0.92
      g/cm(3), providing desired property for bone tissue engineering applications.
      Biocomposite foams were prepared via surfactant foaming. Scanning electron
      microscopic characterization revealed pore size of 200-500 microm of the
      biocomposite foams. When these materials were incubated in simulated body fluid,
      hydroxyapatite layer formation was observed on the material surface. To confirm
      the cell viability and proliferation on these materials, MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed with
      NIH 3T3 fibroblast cells and the results revealed good biocompatibility with the
      biocomposite foams. Cell adhesion studies further confirmed the biocompatibility
      of the scaffolds via cell attachment and ECM production. The optimally
      synthesized biocomposite foams had a good combination of physical properties with
      compressive strength of 1.64 MPa and elastic modulus of 18 MPa. In view of the
      favorable combination of physical and biological properties, the newly developed
      materials are considered to be suitable for regeneration of trabecular bone.

PMID- 19588234
TI  - Photobleaching-based quantitative analysis of fluorescence resonance energy
      transfer inside single living cell.
AB  - The current advances of fluorescence microscopy and new fluorescent probes make
      fluorescence resonance energy transfer (FRET) a powerful technique for studying
      protein-protein interactions inside living cells. It is very hard to
      quantitatively analyze FRET efficiency using intensity-based FRET imaging
      microscopy due to the presence of autofluorescence and spectral crosstalks. In
      this study, we for the first time developed a novel photobleaching-based method
      to quantitatively detect FRET efficiency (Pb-FRET) by selectively photobleaching
      acceptor. The Pb-FRET method requires two fluorescence detection channels: a
      donor channel (CH ( 1 )) to selectively detect the fluorescence from donor, and a
      FRET channel (CH ( 2 )) which normally includes the fluorescence from both
      acceptor and donor due to emission spectral crosstalk. We used the Pb-FRET method
      to quantitatively measure the FRET efficiency of SCAT3, a caspase-3 indicator
      based on FRET, inside single living cells stably expressing SCAT3 during STS
      induced apoptosis. At 0, 6 and 12 h after STS treatment, the FRET efficiency of
      SCAT3 obtained by Pb-FRET inside living cells was verified by two-photon
      excitation (TPE) fluorescence lifetime imaging microscopy (FLIM). The temporal
      resolution of Pb-FRET method is in second time-scale for ROI photobleaching, even
      in microsecond time-scale for spot photobleaching. Our results demonstrate that
      the Pb-FRET method is independent of photobleaching degree, and is very useful
      for quantitatively monitoring protein-protein interactions inside single living
      cell.

PMID- 19588236
TI  - Fundamental movement skills in children diagnosed with autism spectrum disorders
      and attention deficit hyperactivity disorder.
AB  - The purpose of this study was to compare the movement skills of children with
      autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD),
      and those without disabilities. Ninety-one children (ASD, n = 28; ADHD, n = 29;
      control, n = 34), ages 6-10 years, were of average IQ participated. After
      controlling for age, both ASD and ADHD groups scored significantly lower than
      controls (p's < .05) on overall gross motor development as well as locomotor and
      object control subtests, and the ASD group performed more poorly than the ADHD
      group (p's < .01) on both subtests. Of the children with ASD and ADHD, only 16%
      had clinical levels of impairment. Potential underlying factors are discussed,
      with suggestions for future research.

PMID- 19588235
TI  - Interaction of antitumor alpha-lactalbumin-oleic acid complexes with artificial
      and natural membranes.
AB  - The specific complexes of human alpha-lactalbumin (alpha-LA) with oleic acid
      (OA), HAMLET and LA-OA-17 (OA-complexes), possess cytotoxic activity against
      tumor cells but the mechanism of their cell penetration remains unclear. To
      explore the molecular mechanisms underlying interaction of the OA-complexes with
      the cell membrane, their interactions with small unilamellar
      dipalmitoylphosphatidylcholine (DPPC) vesicles and electroexcitable plasma
      membrane of internodal native and perfused cells of the green alga Chara
      corallina have been studied. The fractionation (Sephadex G-200) of mixtures of
      the OA-complexes with the vesicles shows that OA-binding increases the affinity
      of alpha-LA to DPPC vesicles. Calcium association decreases protein affinity to
      the vesicles; the effect being less pronounced for LA-OA-17. The voltage clamp
      technique studies show that LA-OA-17, HAMLET, and their constituents produce
      different modifying effects on the plasmalemmal ionic channels of the Chara
      corallina cells. The irreversible binding of OA-complexes to the plasmalemma is
      accompanied by changes in the activation-inactivation kinetics of developing
      integral transmembrane currents, suppression of the Ca(2+) current and Ca(2+)
      activated Cl(-) current, and by increase in the nonspecific K(+) leakage
      currents. The latter reflects development of nonselective permeability of the
      plasma membrane. The HAMLET-induced effects on the plasmalemmal currents are less
      pronounced and potentiated by LA-OA-17. The control experiments with OA and
      intact alpha-LA show their qualitatively different and much less pronounced
      effects on the transmembrane ionic currents. Thus, the modification of alpha-LA
      by OA results in an increase in the protein association with the model lipid
      bilayer and in drastic irreversible changes in permeability of several types of
      the plasmalemmal ionic channels.

PMID- 19588237
TI  - Sex typicality and attractiveness in childhood and adulthood: assessing their
      relationships from videos.
AB  - Prior research suggests that sex typicality (especially femininity of females,
      but also masculinity of males) relates to perceptions of attractiveness, for both
      heterosexual and homosexual individuals. Using videos from childhood and
      adulthood, we investigated how different components of sex typicality contributed
      to this effect, whether the sex of the evaluator or of the target moderated the
      effect, and how the relationship of attractiveness with sex typicality varied
      across the lifespan. In Study 1, videos of 45 female and 50 male heterosexual and
      homosexual adult targets (ages 18-30 years) were judged by 56 female and 65 male
      heterosexual and homosexual raters (ages 18-30 years). Results suggested that
      both heterosexual men and lesbians viewed more feminine women as more attractive.
      Femininity of appearance was a primary contributor to this relationship.
      Masculinity was not related to men's attractiveness. Study 2 used similar
      methodology (44 male and 46 female heterosexual and homosexual targets and 22
      male and 20 female heterosexual raters). Study 2 replicated results of Study 1.
      In addition, Study 2 included ratings of childhood videos of targets (ages 0-15).
      Results suggested that childhood femininity related to attractiveness of both
      young girls and young boys and that the relationship became stronger for girls as
      they got older. The impact of femininity on attractiveness may, therefore, depend
      on both targets' sex and their maturity.

PMID- 19588238
TI  - Sexual orientation and psychiatric vulnerability: a twin study of neuroticism and
      psychoticism.
AB  - Recent evidence indicates that homosexuals and bisexuals are, on average, at
      greater risk for psychiatric problems than heterosexuals. It is assumed with some
      supporting evidence that prejudice often experienced by nonheterosexuals makes
      them more vulnerable to psychiatric disorder, but there has been no investigation
      of alternative explanations. Here we used Eysenck's Neuroticism and Psychoticism
      scales as markers for psychiatric vulnerability and compared heterosexuals with
      nonheterosexuals in a community-based sample of identical and nonidentical twins
      aged between 19 and 52 years (N = 4904). Firstly, we tested whether apparent
      sexual orientation differences in psychiatric vulnerability simply mirrored sex
      differences-for our traits, this would predict nonheterosexual males having
      elevated Neuroticism scores as females do, and nonheterosexual females having
      elevated Psychoticism scores as males do. Our results contradicted this idea,
      with nonheterosexual men and women scoring significantly higher on Neuroticism
      and Psychoticism than their heterosexual counterparts, suggesting an overall
      elevation of psychiatric risk in nonheterosexuals. Secondly, we used our
      genetically informative sample to assess the viability of explanations invoking a
      common cause of both nonheterosexuality and psychiatric vulnerability. We found
      significant genetic correlation between sexual orientation and both Neuroticism
      and Psychoticism, but no corresponding environmental correlations, suggesting
      that if there is a common cause of both nonheterosexuality and psychiatric
      vulnerability it is likely to have a genetic basis rather than an environmental
      basis.

PMID- 19588240
TI  - Consistency of self-reported sexual behavior in surveys.
AB  - Accurate data on sexual behavior have become increasingly important for
      demographers and epidemiologists, but self-reported data are widely regarded as
      unreliable. We examined the consistency in the number of sexual partners reported
      by participants in seven population-based surveys of adults in the U.S.
      Differences between studies were quite modest and much smaller than those
      associated with demographic attributes. Surprisingly, the mode of survey
      administration did not appear to influence disclosure when the questions were
      similar. We conclude that there is more consistency in sexual partnership
      reporting than is commonly believed.

PMID- 19588241
TI  - Much adieu about not so much.

PMID- 19588239
TI  - Compulsive sexual behavior and risk for unsafe sex among internet using men who
      have sex with men.
AB  - The present study explored the relationship between compulsive sexual behavior
      (CSB) and unprotected anal intercourse (UAI) for men who have sex with men (MSM)
      across a number of ethnic/racial groups and who used the Internet to seek sexual
      partners. A sample of 2,716 MSM (512 Asian, 445 Black, 683 Latino, 348 Other, 728
      White) completed on online survey that collected information about their sexual
      behaviors with partners met online and offline. The survey also included the
      Compulsive Sexual Behavior Inventory (CSBI). Consistent with the notion that CSB
      is a stable trait, higher scores on the CSBI were associated with greater odds
      for engaging in UAI, regardless of the context in which sex partners were met
      (online or offline). Differences in median CSB scores were generally similar
      across racial and ethnic groups. The median CSB score was significantly higher
      for HIV-positive participants than for HIV-negative participants. HIV-prevention
      interventions are needed among MSM, but should take into account that some may be
      resistant to risk reduction strategies because of CSB.

PMID- 19588242
TI  - Misconstruing sex therapy's dilemmas: the need for sexualwissenschaft, sex
      education, and primary prevention.

PMID- 19588243
TI  - Governance of sexual functioning by general vs. special psychological mechanisms
      remains an empirical issue.

PMID- 19588244
TI  - Low genetic variability of domestic Muscovy duck (Cairina moschata) in China
      revealed by mitochondrial DNA control region sequences.

PMID- 19588245
TI  - Novel proteoglycan glycotechnology: chemoenzymatic synthesis of chondroitin
      sulfate-containing molecules and its application.
AB  - Proteoglycans consist of a protein core, with one or more glycosaminoglycan
      chains (i.e., chondroitin sulfate, dermatan sulfate and heparin sulfate) bound
      covalently to it. The glycosaminoglycan chains account for many of the functions
      and properties of proteoglycans. The development of proteoglycan glycotechnology
      to exploit the functionality of glycosaminoglycan chains is an extremely
      important aspect of glycobiology. Here we describe an efficient and widely
      applicable method for chemoenzymatic synthesis of conjugate compounds comprising
      intact long chondroitin sulfate (ChS) chains. An alkyne containing ChS was
      prepared by an enzymatic transfer reaction and linked with a chemically
      synthesized core compound containing an azido group using click chemistry. This
      method enabled highly efficient introduction of ChS into target materials.
      Furthermore, the ChS-introduced compounds had marked stability against
      proteolysis, and the chemically linked ChS chain contributed to the stability of
      these core compounds. We believe the present method will contribute to the
      development of proteoglycan glycobiology and technology.

PMID- 19588247
TI  - Special issue in honor of Dr. Graham A. R. Johnston.

PMID- 19588246
TI  - Purification and characterization of lysophospholipase C from pig brain.
AB  - In present study, lysophospholipase C (lysoPLC) was purified from homogenate of
      pig brain. LysoPLC was purified from brain membranes by procedures employing
      acetic acid precipitation, 1-butanol solubilization and ammonium sulfate
      fractionation, and chromatographies. In SDS-PAGE, the purified enzyme protein was
      relatively homogeneous with molecular mass of around 65 kDa. The lysoPLC activity
      possesses an optimal pH of 8.5, and Km and Vm values of 120.3 microM, and 141.6
      micromole/h/mg protein, respectively for 1-lauroyl lysophosphatidylcholine(LPC),
      and 72.4 microM and 89.8 micromole/h/mg protein for glycerophosphorylcholine
      (GPC). In thermal denaturation at 60 degrees C, the enzyme expressed the same
      inactivation pattern in the hydrolysis of 1-lauroyl LPC and GPC. In the structure
      activity relationship, catalytic efficacy (Vm/Km value) was the greatest for 1
      docosahexaenoyl LPC, followed by 1-arachidonoyl LPC, GPC, 1-hexanoyl LPC, 1
      lauroyl LPC, 1-linoleoyl LPC, 1-myristoyl LPC and 1-oleoyl LPC. Metal ion
      requirement indicates that Zn(2+) was crucial for lysoPLC activity. Noteworthy,
      in the inhibition by oxyanions, the enzyme was selectively and noncompetitively
      inhibited by tellurite ions with Ki value of 0.16 and 0.18 microM in hydrolyzing
      1-lauroyl LPC and GPC, respectively. Taken together, it is suggested that
      lysoPLC, possessing broad substrate specificity, may be implicated in the supply
      of phosphocholine in brain tissue.

PMID- 19588249
TI  - Electromagnetic field at 15.95-16 Hz is cardio protective following acute
      myocardial infarction.
AB  - Previous studies have shown that pre-exposure of the heart to weak magnetic field
      reduces infarct size shortly after induction of myocardial ischemia. To
      investigate the role of AC magnetic field with a frequency of 15.95-16 Hz and 80
      mT on left ventricular (LV) remodeling following chronic coronary occlusion and a
      short episode of ischemia followed by reperfusion (I/R). LV dimension and
      function were measured using echocardiography. Femur bone marrow was isolated and
      cells were phenotyped for endothelial linage and immuno stained for endothelial
      cells. The area at risk was measured using triphenyltetrazolium chloride
      staining. A significant reduction of 27% in shortening fraction (SF) was measured
      following acute myocardial infarction (AMI) compared with a 7% decrease in
      animals exposed to magnetic field (p < 0.04). A significantly higher number of
      colony forming units and endothelial progenitor cells were counted within the
      treated groups subjected to magnetic field (p < 0.02). Exposing the heart to
      magnetic field prior to reperfusion did not show any preservation either on SF or
      on infarct size. Magnetic field was protective in the AMI but not in the I/R
      model. The mechanisms underlying cardiac protection induced by AC magnetic field
      following chronic injury deserves further investigation.

PMID- 19588248
TI  - Soluble dietary fiber protects against nonsteroidal anti-inflammatory drug
      induced damage to the small intestine in cats.
AB  - PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the
      small intestine in humans, but there are few effective agents for treatment of
      small intestinal ulcers. We found that soluble dietary fibers (SDFs), such as
      pectin, could prevent the formation of small intestinal lesions induced by
      indomethacin (IND) in cats. To elucidate the mechanism of protection by SDFs, we
      examined the viscosities of SDFs and the effects of pectin on gastrointestinal
      absorption of IND and intestinal hypermotility induced by IND. METHODS: Cats were
      given regular dry food (RFD-Dry) or RFD-Dry supplemented with pectin, guar gum,
      polydextrose, or mucin twice daily. IND was administered orally once daily for 3
      days. Mucosal lesions in the small intestine were examined 24 h after the final
      dosing of IND. Plasma concentrations of IND were measured by HPLC. GI motilities
      were measured using a telemetry system in conscious cats implanted with force
      transducers. Viscosities of the SDFs were measured using a viscosimeter. RESULTS:
      In cats given RFD-Dry, IND (3 mg/kg) increased motility and produced many lesions
      in the lower half of the small intestine; the total lesion area (TLA) was 7.5 +/-
      2.6 cm(2) (n = 4). Lesions induced by IND were markedly decreased in cats given
      RFD-Dry supplemented with 3% pectin, guar gum, polydextrose or mucin; TLAs were
      0.6 +/- 0.3, 0.0 +/- 0.0, 1.3 +/- 0.8 and 1.6 +/- 0.5 cm(2) (n = 4) (P < 0.05 vs.
      RFD-Dry alone), respectively. The viscosity (mPa-S) of pectin, guar gum,
      polydextrose and mucin (3% concentration) was 414, >1,200, 1 and 4, respectively.
      Pectin did not affect the absorption of IND nor did it inhibit IND-induced
      intestinal hypermotility. CONCLUSIONS: SDFs protect the small intestine against
      NSAID-induced damage, probably by compensating a barrier function of the mucin
      decreased by IND. Viscosities of the SDFs play a role, at least in part, in the
      protective effects of the SDFs on the small intestine.

PMID- 19588250
TI  - Effect of extracellular potassium accumulation on muscle fiber conduction
      velocity: a simulation study.
AB  - A progressive reduction in muscle fiber conduction velocity is typically observed
      during fatiguing muscle contraction. Although the exact causes of the conduction
      velocity decrease have not yet been fully established, increasing evidence
      suggests that changes in extracellular potassium concentration may be largely
      responsible. In this study, a mathematical model was developed to examine the
      effect of extracellular potassium concentration on the muscle fiber action
      potential and conduction velocity. The model was used to simulate changes in
      extracellular potassium concentration at a range of temperatures and
      extracellular potassium accumulation during repetitive stimulation of the muscle
      fiber at 37 degrees C. The action potential broadened, and its amplitude and
      conduction velocity decreased as extracellular potassium concentration increased.
      The potassium-induced changes in action potential shape and conduction velocity
      were eliminated when the inward rectifier channels were removed from the model.
      The results support the hypothesis that accumulation of extracellular potassium
      ions may be a major contributor to the reduction in muscle fiber conduction
      velocity and loss of membrane excitability during fatiguing contractions. They
      additionally suggest that inward rectifier currents play a critical role in
      potassium-induced membrane depolarization, leading to increased sodium
      inactivation and resulting in the observed reduction in conduction velocity and
      membrane excitability.

PMID- 19588251
TI  - Instrumental music influences recognition of emotional body language.
AB  - In everyday life, emotional events are perceived by multiple sensory systems.
      Research has shown that recognition of emotions in one modality is biased towards
      the emotion expressed in a simultaneously presented but task irrelevant modality.
      In the present study, we combine visual and auditory stimuli that convey similar
      affective meaning but have a low probability of co-occurrence in everyday life.
      Dynamic face-blurred whole body expressions of a person grasping an object while
      expressing happiness or sadness are presented in combination with fragments of
      happy or sad instrumental classical music. Participants were instructed to
      categorize the emotion expressed by the visual stimulus. The results show that
      recognition of body language is influenced by the auditory stimuli. These
      findings indicate that crossmodal influences as previously observed for
      audiovisual speech can also be obtained from the ignored auditory to the attended
      visual modality in audiovisual stimuli that consist of whole bodies and music.

PMID- 19588252
TI  - Stress responses to heterologous membrane protein expression in Escherichia coli.
AB  - The stress response of E. coli to the expression of two recombinant membrane
      proteins, the E. coli AAA+ protease FtsH and the human G-protein coupled receptor
      CB1, was examined using several members of a promoter-GFP library. Several genes
      from the heat-shock and envelope stress regulons (rpoH, clpP, lon, and ftsH) were
      strongly induced by expression of either membrane protein. Flow cytometry was
      used to monitor the real-time dynamics of the transcription of these reporter
      genes in response to membrane protein expression. Co-expression of CB1 and FtsH
      led to an additive response in these four reporter genes suggesting that the
      stresses may be occurring via different physiological mechanisms.

PMID- 19588253
TI  - Production of cyclodextrin glucanotransferase from an alkalophilic Bacillus sp.
      by pH-stat fed-batch fermentation.
AB  - Batch and fed-batch fermentation processes were employed to culture an
      alkalophilic Bacillus sp. for the production of cyclodextrin glucanotransferase
      (CGTase). CGTase production was repressed by glucose and induced by soluble
      starch. By fed-batch fermentation, a CGTase activity up to 56 unit ml(-1) with 65
      g dry cells l(-1) were achieved. The CGTase activity and cell density were
      increased 360 and 510%, respectively, from those values achieved with batch
      fermentation.

PMID- 19588254
TI  - Gene expression of halophyte Kosteletzkya virginica seedlings under salt stress
      at early stage.
AB  - Gene differential expression of Kosteletzkya virginica seedlings under salt
      stress at two time points (2, 24 h) in roots and leaves was analyzed using the
      cDNA-amplified fragment length polymorphism (cDNA-AFLP) technique. Polymorphic
      transcript-derived fragments (TDFs) among control plants and salt-treated plants
      were grouped into four main differential expression patterns: repression (A), de
      novo induction (B), up-regulation (C) and down-regulation (D). Among them, 34
      differentially expressed gene fragments were homologous to known genes from other
      species and 4 were sequences with unknown functions. These differentially
      expressed genes can be classified into four groups according to their putative
      functions: (1) genes for re-establishing ion homeostasis and protecting the plant
      from stress damage; (2) genes involved in metabolism or energy and resuming plant
      growth and development under salt stress; (3) genes involved in regulation of
      gene expression; (4) genes for signal transduction. Changes of eight
      differentially expressed genes were confirmed by quantitative real time RT-PCR.

PMID- 19588255
TI  - Microsatellite marker-mediated analysis of the EMBRAPA Rice Core Collection
      genetic diversity.
AB  - The objectives of this study were to determine the genetic structure of 242
      accessions from the EMBRAPA Rice Core Collection (ERiCC), to create a mini-core
      collection and to develop a multiplex panel of fluorescent labeled simple
      sequence repeats (SSRs). Eighty-six SSRs were used to identify 1,066 alleles,
      with an average number of 12.4 alleles/locus and average polymorphism information
      content (PIC)/locus of 0.75. A model-based clustering method recognized the
      structure of the accessions on two levels, according to their cultivation system
      and origin. The most divergent subgroup identified was the worldwide lowland
      accessions, with the highest values for gene diversity (0.75), average Rogers
      distance modified by Wright (0.80), average number of alleles/locus (11.7) and
      private alleles (132). A mini-core was assembled with the most divergent 24
      lowland and upland accessions. This mini-core displayed an average distance of
      0.86, an average number of alleles/locus of 8.4 and an average PIC/locus of 0.8.
      From the 86 SSRs, 24 were selected to compose six multiplex panels in order to
      optimize the process of rice genotyping. This set of markers distinguished all
      242 accessions, and showed an average PIC of 0.80 and an average number of
      alleles/locus of 15.4, higher than the entire set of 86 SSRs. Since the
      heterogeneity found in lines and cultivars of ERiCC was higher than expected, it
      is necessary to analyze pooled DNA samples to get a better estimate of genetic
      variability. The SSR characterization of ERiCC clearly indicates that there is
      high genetic variability in rice accessions stored in genebanks worldwide which
      can be promptly explored by rice pre-breeding programs.

PMID- 19588256
TI  - Evaluation of Mite-Away-II for fall control of Varroa destructor (Acari:
      Varroidae) in colonies of the honey bee Apis mellifera (Hymenoptera: Apidae) in
      the northeastern USA.
AB  - Mite-Away II, a recently-registered product with a proprietary formulation of
      formic acid, was evaluated under field conditions in commercial apiaries in
      upstate New York (USA) for the fall control of Varroa destructor Anderson &
      Trueman in colonies of the honey bee, Apis mellifera L. Ambient temperatures
      during the treatment period were in the lower half of the range recommended on
      the label, but were typical for early fall in upstate New York. Average mite
      mortality was 60.2 +/- 2.2% in the Mite-Away II group and 23.3 +/- 2.6% in the
      untreated control group. These means were significantly different from each
      other, but the level of control was only moderate. These results demonstrate that
      Mite-Away II may not always provide an adequate level of control even when the
      temperature at the time of application falls within the recommended range stated
      on the product's label. To make the best use of temperature-sensitive products, I
      suggest that the current, single-value, economic treatment threshold be replaced
      with an economic treatment range. The limits for this range are specified by two
      pest density values. The lower limit is the usual pest density that triggers a
      treatment. The upper limit is the maximum pest density that one can expect to
      reduce to a level below the lower limit given the temperatures expected during
      the treatment period. When the actual pest density exceeds the upper limit, the
      product should not be recommended; or, a warning should be included indicating
      that acceptable control may not be achieved.

PMID- 19588258
TI  - Disposable electrochemical sensor for rapid measurement of heavy metals in fish
      by square wave anodic stripping voltammetry (SWASV).

PMID- 19588259
TI  - The pattern of toxin genes and expression of diarrheal enterotoxins in Bacillus
      thuringiensis strains isolated from commercial bioinsecticides.

PMID- 19588257
TI  - Immunohistochemical approach reveals involvement of inducible nitric oxide
      synthase in rat late development.
AB  - To better understand the role of nitric oxide (NO) in mammal development,
      specifically in the transition of the fetal stages at birth, we studied the
      timing of cell-specific expression of inducible NO synthase (iNOS) isoform during
      gestational periods of rats, mainly at the late stages of intra-uterine
      development. Before experimentation, the samples were collected (from 17th to
      21st gestational days), fixed in 10% buffered formalin and embedded in paraffin
      for histological procedures. Hereafter, the sections (5 mum thickness) obtained
      from different embryos were immunostained by avidin-biotin-immunoperoxidase
      technique, by using antibody against iNOS isoform. The most of cell
      immunopositive was suggestive of granulocyte-like cells and those cells were
      resident close to the blood vessels in different organs, such as: lung, liver or
      bone marrow environment. Sometimes we noted immunopositive cells in the blood
      flow, as reported in the thymus. In agreement, iNOS expression, obtained by
      western blotting analysis, showed the same profile. Together, our data shows that
      iNOS expression increased gradually during the late stages of rat development
      (from E17 to E21) and it was executed by cells close to blood vessels. Thus, we
      can clearly to predict that this expression was finely modulated and it
      contributes for time-line dependent NO production during rat late development.

PMID- 19588260
TI  - Cytochrome P450 (CYP1A) induction in sea bream (Sparus Aurata) gills and liver
      following exposure to polychlorobiphenyls (PCBs).

PMID- 19588262
TI  - Cystic echinococcosis in the sheep: causes of its persistence in Sardinia.
AB  - The authors analyse the current epidemiological situation of sheep Cystic
      Echinococcosis (CE) in Sardinia, where the prevalence of ovine CE is still very
      high (70%) and this parasitosis is also frequently found in the human population.
      For this reason Sardinia represents a peculiar model for CE study, because there
      are particular conditions that allow Echinococcus granulosus to complete its life
      cycle. Some social and economical factors support the persistence of sheep CE:
      over 3 million Sarda breed heads are extensively bred; the presence, at farm
      level, of a strong relationship between dog, sheep and human; the low commercial
      value of meat coming from adult sheep, which results in a large number of sheep
      being slaughtered at home or on the farm rather than in authorized
      slaughterhouses. Moreover Sardinia is the only Italian region where partially
      successful echinococcosis control plans have been applied. The authors suggest
      some indirect and direct initiatives, including the use of a new vaccine against
      the development of this metacestode in sheep, to reduce the prevalence of CE.

PMID- 19588261
TI  - Helminths and arthropoda in buffalo farms from the Lazio region (Italy).

PMID- 19588263
TI  - State of the art and future trends of European and Italian aquaculture.
AB  - This paper describes the main features of fish aquaculture in Europe and Italy
      focusing attention on single sectors of the farmed species and their trend for
      the future. Over recent years, European and Italian aquaculture have shown a
      markedly different trend from that of world aquatic production. Asia,
      particularly China, has recorded a constant and rapid growth and Latin America a
      moderate development. Nowadays, European farmers are concerned with adapting
      their product to market demand and diversifying the fish species reared. After a
      discussion about the main European production statistics regarding finfish
      aquaculture production, we consider the most important aspects in the promotion
      of production and consequent consumption of farmed fish.

PMID- 19588264
TI  - Optimisation of contained Nicotiana tabacum cultivation for the production of
      recombinant protein pharmaceuticals.
AB  - Nicotiana tabacum is emerging as a crop of choice for production of recombinant
      protein pharmaceuticals. Although there is significant commercial expertise in
      tobacco farming, different cultivation practices are likely to be needed when the
      objective is to optimise protein expression, yield and extraction, rather than
      the traditional focus on biomass and alkaloid production. Moreover,
      pharmaceutical transgenic tobacco plants are likely to be grown initially within
      a controlled environment, the parameters for which have yet to be established.
      Here, the growth characteristics and functional recombinant protein yields for
      two separate transgenic tobacco plant lines were investigated. The impacts of
      temperature, day-length, compost nitrogen content, radiation and plant density
      were examined. Temperature was the only environmental variable to affect IgG
      concentration in the plants, with higher yields observed in plants grown at lower
      temperature. In contrast, temperature, supplementary radiation and plant density
      all affected the total soluble protein yield in the same plants. Transgenic
      plants expressing a second recombinant protein (cyanovirin-N) responded
      differently to IgG transgenic plants to elevated temperature, with an increase in
      cyanovirin-N concentration, although the effect of the environmental variables on
      total soluble protein yields was the same as the IgG plants. Planting density and
      radiation levels were important factors affecting variability of the two
      recombinant protein yields in transgenic plants. Phenotypic differences were
      observed between the two transgenic plant lines and non-transformed N. tabacum,
      but the effect of different growing conditions was consistent between the three
      lines. Temperature, day length, radiation intensity and planting density all had
      a significant impact on biomass production. Taken together, the data suggest that
      recombinant protein yield is not affected substantially by environmental factors
      other than growth temperature. Overall productivity is therefore correlated to
      biomass production, although other factors such as purification burden,
      extractability protein stability and quality also need to be considered in the
      optimal design of cultivation conditions.

PMID- 19588265
TI  - Multiple copies of rosR and pssA genes enhance exopolysaccharide production,
      symbiotic competitiveness and clover nodulation in Rhizobium leguminosarum bv.
      trifolii.
AB  - Rhizobium leguminosarum bv. trifolii exopolysaccharide (EPS) plays an important
      role in determining symbiotic competence. The pssA gene encoding the first
      glucosyl-IP-transferase and rosR encoding a positive transcriptional regulator
      are key genes involved in the biosynthesis and regulation of EPS production.
      Mutation in pssA resulted in deficiency in EPS production and rosR mutation
      substantially decreased the amount of EPS. Both mutants induced nodules but the
      bacteria were unable to fix nitrogen. Defective functions of pssA and rosR
      mutants were fully restored by wild type copies of the respective genes.
      Introduction of multiple rosR and pssA gene copies on the plasmid vector pBBR1MCS
      2 into five R. leguminosarum bv. trifolii nodule isolates resulted in
      significantly increased growth rates, EPS production and the number of nodules on
      clover roots. Increase in fresh and dry shoot mass of clovers and nodule
      occupation was also statistically significant. Interestingly, additional copies
      of pssA but particularly rosR gene, increased strains' competitiveness in
      relation to the wild type parental strains nearly twofold. Overall, experimental
      evidence is provided that increased amount of EPS beneficially affects R.
      leguminosarum bv. trifolii competitiveness and symbiosis with clover.

PMID- 19588266
TI  - Acute hemolysis after receiving oxaliplatin treatment: a case report and
      literature review.
AB  - OBJECTIVE: To report a case of immune mediated hemolysis occurring after
      oxaliplatin infusion in a patient with rectal cancer. CASE SUMMARY: We report a
      69 year old male patient who presented with acute onset anemia after infusion of
      oxaliplatin as chemotherapy. A positive direct Coombs test and good response to
      steroids treatment underlined the diagnosis of immune related hemolytic anemia.
      The patient was switched to irinotecan-based chemotherapy regimen for further
      treatment. DISCUSSION: To our knowledge, there has been less than 10 cases of
      hemolysis occurring after oxaliplatin treatment in the medical literature. In all
      cases, immune mediated hemolysis has been proven with a positive coombs test. As
      oxaliplatin based chemotherapy regimen has become a standardized first line
      treatment for metastatic colorectal adenocarcinoma, this phenomenon warrants a
      higher level of physician awareness. CONCLUSIONS: Oxaliplatin related hemolytic
      anemia is a rare reported phenomenon. Patient under oxaliplatin treatment
      presenting with sudden hemoglobin decrease should prompt further investigation of
      hemolysis.

PMID- 19588267
TI  - Measurement of patient satisfaction with community pharmacy services: a review.
AB  - AIM OF THE REVIEW: The aim of this review is to conduct an in-depth analysis of
      the available literature in order to identify and evaluate studies measuring
      patient satisfaction with pharmacy services delivered by pharmacists in a
      community setting. METHOD: An extensive literature search was conducted in five
      databases (Medline, Scopus, Embase, Psychinfo, International Pharmaceutical
      Abstracts) using the search terms "patient/client/consumer satisfaction" AND
      "community pharmacy/pharmacies" AND "pharmacy service/pharmaceutical
      services/pharmacy program/intervention/intervention studies". Only those articles
      where the main focus was measuring patient satisfaction with services delivered
      in community pharmacies were included in the review. Patient satisfaction was
      explored with three different levels of pharmacy services -- general services,
      intervention services and cognitive services. RESULTS: Twenty-four articles
      measuring patient satisfaction with community pharmacy services were retrieved.
      Of these, eleven measured patient satisfaction with general services, six
      measured satisfaction with intervention services and seven measured satisfaction
      with cognitive services. The majority of studies reviewed had adopted and
      measured satisfaction as a multidimensional construct. None of the studies
      reviewed tested any theoretical models of satisfaction. Further a lack of
      consistent instruments measuring patient satisfaction was observed, with most of
      the reviewed studies using self developed, non-validated or ad hoc instruments
      with items from various previously published papers. The review also observed
      high levels of patient satisfaction with pharmacy services be they general,
      intervention or cognitive services. CONCLUSION: This review found that patient
      satisfaction has been measured within the community pharmacy context to a certain
      degree. Further research is needed to develop and test instruments based on
      theoretical frameworks, to test satisfaction pre and post hoc and in well
      designed randomized controlled trials and to measure changes in satisfaction over
      time. Novel approaches involving an understanding of expectations and preferences
      of patients and matching these to the services provided also need to be explored.

PMID- 19588268
TI  - Retinitis pigmentosa and mucopolysaccharidosis type II: an extremely attenuated
      phenotype.

PMID- 19588269
TI  - Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and
      propionic acidaemias.
AB  - BACKGROUND: Insulin-resistant hyperglycaemia may occasionally complicate the
      clinical course of organic acidaemias. STUDY DESIGN: Clinical observation.
      RESULTS: Two term infants, one suffering from acute early-onset methylmalonic
      acidaemia, the other suffering from acute early-onset propionic acidaemia,
      presented acutely with dehydration, ketoacidosis, and hyperammonaemia. Urinary
      organic acid, plasma amino acids, and blood and plasma acylcarnitine analysis
      allowed the diagnosis of methylmalonic and propionic acidaemias. The detection of
      the novel c.481G>A (p.Gly161Arg) and the known c.655A>T (p.Asn219Tyr) MUT gene
      mutations identified the first patient as affected by methylmalonic acidaemia mut
      type. The high increase of propionylcarnitine after carnitine administration in
      both patients suggested a greatly elevated metabolic intoxication. Both newborns
      showed insulin-resistant hyperglycaemia. Patient 1 died, but patient 2, after a
      strong reduction of glucose administration, survived. To our knowledge, this is
      the only patient with this complication who survived. CONCLUSION: Insulin
      resistant hyperglycaemia complicating neonatal onset of methylmalonic and
      propionic acidaemias is probably a marker of a serious disease. One patient with
      this complication survived after a strong reduction of glucose administration.
      Even if this is probably only a partial intervention, we hypothesize that in this
      situation a reduction of glucose administration can reduce almost the risk of
      persistent hyperglycaemia. Further studies are required to confirm our
      hypothesis.

PMID- 19588270
TI  - Danon disease: case report and detection of new mutation.
AB  - Danon disease is an X-linked disorder resulting from mutations in the lysosome
      associated membrane protein-2 (LAMP2) gene. We report a male patient with
      skeletal myopathy, mental retardation, and massive hypertrophic obstructive
      cardiomyopathy necessitating heart transplantation. Immunohistochemistry of
      skeletal muscle and leukocytes, western blot analysis of leukocytes and cardiac
      muscle, flow cytometry, and DNA sequencing were performed. Muscle biopsy revealed
      autophagic vacuolar myopathy and lack of immunohistochemically detectable LAMP-2.
      Diagnosis of Danon disease was confirmed by western blot analysis of myocardial
      tissue and peripheral blood sample of the patient showing deficiency of LAMP-2 in
      myocardium and leukocytes. Moreover, absence of LAMP-2 in lymphocytes, monocytes
      and granulocytes was shown by flow cytometric analysis. Genetic analysis of the
      LAMP2 gene revealed a novel 1-bp deletion at position 179 (c.179delC) at the 3'
      end of exon 2, resulting in a frameshift with a premature stop codon.

PMID- 19588271
TI  - Italian translation of the Manchester-Oxford Foot Questionnaire, with re
      assessment of reliability and validity.
AB  - PURPOSE: To cross-culturally adapt and validate the Italian version of the
      Manchester-Oxford Foot Questionnaire (MOXFQ) in patients affected by hallux
      valgus. METHODS: The MOXFQ was translated into Italian and culturally adapted
      following the forward and backward translation method. A sample of 172 patients
      with hallux valgus was asked to fill in the MOXFQ and the Short-Form 36 Health
      Survey (SF-36). Two-week retest was performed on a random sub-sample of 40
      patients. Internal consistency and test-retest reliability were assessed using
      Cronbach's alpha and intraclass correlation coefficient (ICC), respectively.
      Construct validity was assessed with the use of Spearman's rank correlation
      coefficient, using a priori hypothesized correlations with SF-36 domains.
      RESULTS: The internal consistency reliability was acceptable for all MOXFQ
      domains (Pain, Walking/standing and Social interaction) with Cronbachs' alpha
      coefficients ranging from 0.72 to 0.83. The assessment of test-retest reliability
      reveals satisfactory values with ICCs ranging from 0.85 to 0.92. Construct
      validity was supported by the presence of all the hypothesized correlation, with
      the exception of Italian Walking/standing domain with the SF-36 Role-Physical
      domain (rho = -0.29). CONCLUSIONS: The Italian version of MOXFQ is a valid and
      reliable instrument for evaluating foot pain and functional status in patients
      affected by hallux valgus.

PMID- 19588274
TI  - Mitochondrial DNA and Y-chromosome variation in five eastern Aleut communities:
      evidence for genetic substructure in the Aleut population.
AB  - Since Russian contact in 1741, the Aleut communities of southwestern Alaska have
      undergone a series of demographic upheavals stemming from forced relocations,
      disease epidemics, population bottlenecks, and pervasive admixture with European
      populations. This study investigates the impact of key historical events on the
      genetic structure of the Aleut population through analysis of mitochondrial and Y
      chromosome DNA variation in five eastern Aleut communities. Results from HVS-I
      sequencing and Y-chromosome typing reveal patterns of variability that exhibit
      east-west geographic differentiation for the major Aleut haplogroups. This
      finding is underscored by SAMOVA and Monmonier analyses that identify genetic
      discontinuities between eastern and western Aleut populations. The majority of
      Aleut Y-chromosomes were characterized to haplogroups of mostly Russian,
      Scandinavian and Western European origin (approximately 85%), which is in stark
      contrast to the 3.6% of Aleut mtDNA lineages identified as non-Native American,
      and thus indicating a large degree of asymmetrical gene flow between European men
      and Aleut women. Overall, this study identifies a significant relationship
      between geography and genetic variation in the Aleut population, with a distinct
      substructure along an east-west axis that reflects the combined effects of
      founder events in aggregate island communities, male-biased gene flow from
      European populations, and the original peopling of the Aleutian Archipelago.

PMID- 19588273
TI  - Early EEG monitoring for detecting postanoxic status epilepticus during
      therapeutic hypothermia: a pilot study.
AB  - OBJECTIVE: To determine whether routine electroencephalography (EEG) detected
      electrical status epilepticus (ESE), masked by neuromuscular blockade, in
      comatose cardiac-arrest survivors receiving therapeutic hypothermia. DESIGN:
      Prospective 3-year study. SETTING: Medical ICU. PATIENTS: Fifty-one consecutive
      comatose cardiac-arrest patients treated between May 2005 and May 2008 using a
      standardized protocol of hypothermia with neuromuscular blockade. INTERVENTION:
      EEG was performed routinely as soon as possible after starting therapeutic
      hypothermia. EEG recordings were read by an independent neurophysiologist who was
      blinded to patient data. MEASUREMENTS AND MAIN RESULTS: Median body temperature
      at EEG recording was 33.0 degrees C (range 32.4-33.8). ESE was found on 5 (10%)
      of the 51 EEG recordings: three patients had continuous rhythmic generalized
      spikes and two patients had continuous rhythmic focal spike-waves. Of the 17
      (33%) patients who were discharged alive, 8 (8/51, 16%) had a CPC score of 1, 4
      (8%) of 2, and 5 (10%) of 3. All patients with ESE died during their ICU stay.
      CONCLUSION: These preliminary results indicate that postanoxic status epilepticus
      can be masked by neuromuscular blockade during our protocol of therapeutic
      hypothermia. Routine EEG monitoring might be helpful in cardiac-arrest survivors
      receiving therapeutic hypothermia. Further studies including continuous EEG
      monitoring are needed to determine whether early diagnosis and treatment of ESE
      during therapeutic hypothermia improves the outcome.

PMID- 19588275
TI  - Induced abortion among HIV-positive women in Northern Vietnam: exploring
      reproductive dilemmas.
AB  - Across the world, childbearing among HIV-positive women is a socially
      controversial issue. This paper derives from a larger research project that
      investigated reproductive decisions among HIV-positive women in Quang Ninh, a
      northern province of Vietnam. The paper focuses on 13 women who had an abortion
      after being diagnosed as HIV-positive, exploring their reflections, concerns and
      dilemmas. The results show that the HIV-positive pregnant women sought to balance
      their desires for a child with their worries of being unable to fulfill their
      responsibilities as mothers. Even while strongly desiring to become mothers,
      women in this study opted to terminate their pregnancies out of fear that they
      could not care adequately for the child they expected. These results indicate
      that when providing reproductive health counselling and support for HIV-positive
      women and their families, it is essential to take into account the socio-cultural
      factors that shape women's reproductive options.

PMID- 19588272
TI  - Tissue elasticity and the ageing elastic fibre.
AB  - The ability of elastic tissues to deform under physiological forces and to
      subsequently release stored energy to drive passive recoil is vital to the
      function of many dynamic tissues. Within vertebrates, elastic fibres allow
      arteries and lungs to expand and contract, thus controlling variations in blood
      pressure and returning the pulmonary system to a resting state. Elastic fibres
      are composite structures composed of a cross-linked elastin core and an outer
      layer of fibrillin microfibrils. These two components perform distinct roles;
      elastin stores energy and drives passive recoil, whilst fibrillin microfibrils
      direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via
      TGFbeta sequestration and potentially act to reinforce the elastic fibre. In many
      tissues reduced elasticity, as a result of compromised elastic fibre function,
      becomes increasingly prevalent with age and contributes significantly to the
      burden of human morbidity and mortality. This review considers how the unique
      molecular structure, tissue distribution and longevity of elastic fibres pre
      disposes these abundant extracellular matrix structures to the accumulation of
      damage in ageing dermal, pulmonary and vascular tissues. As compromised
      elasticity is a common feature of ageing dynamic tissues, the development of
      strategies to prevent, limit or reverse this loss of function will play a key
      role in reducing age-related morbidity and mortality.

PMID- 19588278
TI  - Extending the critical aspects of the water access indicator using East Africa as
      an example.
AB  - The United Nations has declared 2005-2015 the Fresh Water Decade in which more
      people than ever before will gain access to water. Despite acknowledging that
      water quantity is important to health, so far only water quality is used in
      monitoring the Millennium Development Goals. This study examines the changes in
      national access figures when both water quality and quantity are taken into
      account to determine access. Using East Africa as an example shows that the
      number of people with access to water for the region decreased by 9% (7% urban
      and 10% rural). The largest difference in access is observed in Eritrea 25% (11%
      urban and 36% rural). Reduction is higher in rural areas. However, significant
      reduction in access is also observed in urban Ethiopia (14%). In conclusion, the
      indicators for access to water would be better articulated by adding water
      quantity to the indicator which currently only includes water quality, while the
      Demographic Health Survey and Multiple Indicator Cluster Survey routinely
      collects information on both aspects.

PMID- 19588279
TI  - Antifungal activity of Syzygium cumini against Ascochyta rabiei-the cause of
      chickpea blight.
AB  - Aqueous, ethanol and n-hexane extracts from leaves, fruit, root-bark and stem
      bark of Syzygium cumini (L.) Skeels were tested for their antifungal activity
      against Ascochyta rabiei (Pass.) Lab., the cause of blight disease of the
      chickpea (Cicer arietinum L.). Different concentrations, namely 1, 2, ..., 5% of
      both aqueous and the two organic solvent extracts were used in this study.
      Aqueous extracts of all the four test plant parts, namely leaves, fruit, stem
      bark and root-bark, showed significant antifungal activity resulting in 7-30%, 22
      59%, 23-39% and 21-64% reduction in fungal growth, respectively. Similarly, n
      hexane stem-bark extract, and ethanol root- and stem-bark extracts also
      significantly suppressed the growth of target fungal species, resulting in 17
      39%, 24-30% and 12-32% suppression in fungal growth.

PMID- 19588280
TI  - Trans-adapting outcome measures in rehabilitation: Cross-cultural issues.
AB  - Most outcome measures in rehabilitation are developed in the US and are later
      translated and used in the international rehabilitation community. Translating or
      rather trans-adapting outcome measures is an important process by which treatment
      efficacy can be proven and comparability can be established across cultures. This
      article explores some of the pitfalls the lack of adherence to international
      trans-adaptation guidelines can result in. We recommend the application of
      increased use of these guidelines in order to improve the quality of trans
      adaptation, strengthen the international rehabilitation community's scientific
      position, and provide enhanced services to our patients.

PMID- 19588281
TI  - Autopsy standards for fetal lengths and organ weights of an Australian   
      perinatal population.
AB  - AIMS: This study aims to establish a complete and accurate set of Australian
      reference ranges to be used during the routine perinatal post-mortem examination.
      Eighteen routinely measured parameters will be analysed for each gestational age
      from 12 weeks to 42 weeks inclusive. METHODS: A retrospective review was
      performed of all perinatal and neonatal autopsies conducted at the Royal Women's
      Hospital (RWH), Melbourne, between 1 January 2001 and 31 December 2006. A total
      of 1116 post-mortem examination reports were analysed for this study. Established
      study design, technical and statistical methodologies were followed. RESULTS:
      Reference ranges comprising mean and standard deviation have been produced,
      together with the 5th, 50th and 95th percentiles for all parameters at each
      gestational age. Graphs demonstrating these data have been developed for each
      parameter. CONCLUSION: This study has established a complete set of reference
      ranges for parameters measured at perinatal post-mortem examinations. As the
      sample population used is truly representative of the mixed immigrant population
      present in Australian society, the reference ranges and percentiles produced in
      this study will be valuable for all perinatal pathologists.

PMID- 19588282
TI  - Is the self special in the dorsomedial prefrontal cortex? An fMRI study.
AB  - In recent years, several neuroimaging studies have suggested that the neural
      basis of the self-referential process1 is special, especially in the medial
      prefrontal cortex (MPFC). However, it remains controversial whether activity of
      the MPFC (and other related brain regions) appears only during the self
      referential process. We investigated the neural correlates during the processing
      of references to the self, close other (friend), and distant other (prime
      minister) using fMRI. In comparison with baseline findings, referential
      processing to the three kinds of persons defined above showed common activation
      patterns in the dorsomedial prefrontal cortex (DMPFC), left middle temporal
      gyrus, left angular gyrus, posterior cingulate cortex and right cerebellum.
      Additionally, percent changes in BOLD signal in five regions of interest
      demonstrated the same findings. The result indicated that DMPFC was not special
      for the self-referential process, while there are common neural bases for
      evaluating the personalities of the self and others.

PMID- 19588283
TI  - Intragastric balloon for weight loss: results in 100 individuals followed for at
      least 2.5 years.
AB  - BACKGROUND AND STUDY AIMS: To determine long-term outcome after treatment with an
      intragastric balloon for 6 months, with no structured weight maintenance program
      offered after balloon removal. PATIENTS AND METHODS: 100 consecutive
      overweight/obese individuals (mean body mass index [BMI] 35.0 +/- 5.6 kg/m (2))
      were prospectively followed after endoscopic implantation of a saline-filled
      intragastric balloon; 97 completed final follow-up at a mean of 4.8 +/- 1.6
      years. Successful intragastric balloon therapy was defined as weight loss at 6
      months of > or = 10 % of weight at baseline, that remained > or = 10 % until 2.5
      years, without bariatric surgery. All analyses followed intention-to-treat
      principles. RESULTS: At 6 months, mean weight loss was 12.6 +/- 8.3 kg, 63
      individuals had > or = 10 % baseline weight loss; no severe morbidity was
      detected. During the first and second years following intragastric balloon
      removal, mean body mass increased by 4.2 +/- 6.8 and 2.3 +/- 6.0 kg, respectively
      ( P < 0.001 for both year-on-year comparisons). At 2.5 years, intragastric
      balloon therapy had been successful in 24 participants. At final follow-up (4.8
      +/- 1.6 years), 28 had > or = 10 % baseline weight loss, 35 had undergone
      bariatric surgery (60 % had preoperative mass higher than baseline), and 3 were
      lost to follow-up; the 34 remaining had lost 1.5 +/- 5.8 kg compared with
      baseline. During follow-up, 13 had a second intragastric balloon implanted and 13
      took sibutramine for short periods. CONCLUSION: Intragastric balloon therapy was
      relatively innocuous and associated with successful weight loss and maintenance
      at 2.5 years in a quarter of participants. It represents a valid option for
      weight loss.

PMID- 19588284
TI  - Topical viscous lidocaine solution versus lidocaine spray for pharyngeal
      anesthesia in unsedated esophagogastroduodenoscopy.
AB  - BACKGROUND AND STUDY AIMS: Pharyngeal anesthesia using topical lidocaine is
      generally used as pretreatment for unsedated esophagogastroduodenoscopy (UEGD).
      The aim of this study was to compare and evaluate the clinical efficacy of
      topical viscous lidocaine solution and lidocaine spray when each is used as a
      single agent for UEGD. PATIENTS AND METHODS: Patients were randomized into the
      viscous lidocaine (V) group (n = 930) or the lidocaine spray (S) group (n = 934).
      The total dose of lidocaine was not higher than 5 mg/kg. The primary objective
      was to measure the successful completion rate of the endoscopy. The secondary
      objectives were to assess patient and endoscopist satisfaction, procedural pain,
      patient tolerance, ease of intubation, and adverse events. RESULTS: The procedure
      was successfully completed in 868 patients from group V (93.3 %) and 931 patients
      from group S (99.7 %; P < 0.001). Patients and endoscopists reported a higher
      degree of satisfaction in group S than group V ( P < 0.0001). Procedural pain
      score in group S was significantly lower than in group V ( P < 0.0001). The
      endoscopist rated patients in group S as having better tolerance and ease of
      intubation than those in group V ( P = 0.0004 and P = 0.002, respectively).
      Adverse events occurred in 370 patients in group V and 316 patients in group S (
      P = 0.002). These were mainly transient changes in vital signs including
      hypertension, tachycardia, and bradycardia. CONCLUSIONS: The use of lidocaine
      spray in UEGD was shown to result in a higher procedural completion rate, greater
      ease of intubation, and greater patient and endoscopist satisfaction. Topical
      lidocaine spray may be a better form of pharyngeal anesthesia than viscous
      lidocaine solution in UEGD.

PMID- 19588285
TI  - Degree of concordance between double-balloon enteroscopy and capsule endoscopy in
      obscure gastrointestinal bleeding: a multicenter study.
AB  - BACKGROUND AND STUDY AIMS: Capsule endoscopy is considered the diagnostic
      procedure of choice in patients with obscure gastrointestinal bleeding (OGIB).
      Double-balloon endoscopy (DBE) offers both diagnostic and therapeutic potential,
      but is invasive, complex, and time-consuming. The aim was to evaluate diagnostic
      agreement between capsule endoscopy and DBE in patients with OGIB, and
      secondarily the diagnostic gain of DBE when capsule endoscopy detected only blood
      or clots in the small-bowel lumen. METHODS: Multicenter prospective study carried
      out at six institutions in Italy. RESULTS: 193 patients (119 men, mean age 61.6
      +/- 16.2) first underwent capsule endoscopy and then DBE. The most frequent
      positive findings at capsule endoscopy were vascular lesions (74 patients, 38.3
      %), blood or clot in the lumen (34, 17.6 %), and tumor mass (20, 10.4 %). The
      most frequent findings at DBE were vascular lesions (72 patients, 37.3 %),
      neoplasia (30, 15.5 %) and ulcers/inflammatory lesions (12, 6.2 %). Overall kappa
      coefficient was 0.46 (95 %CI 0.38 - 0.54), with maximum concordance for vascular
      (0.72 [95 %CI 0.59 - 0.84]) and inflammatory (0.78 [0.58 - 0.99]) lesions and
      minimum for polyps (0.46 [0.16 - 0.80]). Blood in the lumen was the only positive
      finding at capsule endoscopy in 34 cases; of these, 12 had negative DBE findings
      whereas 10 had vascular lesions, 6 neoplasia, 1 ulcer, and 5 diverticula.
      CONCLUSION: Capsule endoscopy and DBE have good agreement for vascular and
      inflammatory lesions but not for polyps or neoplasia. DBE provides valuable
      adjunctive information, particularly in patients with neoplasia or polyp at
      capsule endoscopy. DBE clarified the origin of bleeding in two-thirds of patients
      with capsule endoscopy showing only blood in the lumen.

PMID- 19588286
TI  - Complication rates of EUS-guided celiac plexus blockade and neurolysis: results
      of a large case series.
AB  - BACKGROUND AND STUDY AIMS: Complication rates for EUS-guided celiac plexus
      blockade (CPB) and celiac plexus neurolysis (CPN) have been largely derived from
      studies utilizing percutaneous or surgical techniques, with few studies
      specifically examining rates for EUS-guided CPB and CPN. This study aims to
      further describe the complication rates of EUS-guided CPB and CPN. PATIENTS AND
      METHODS: In a retrospective analysis of a prospectively collected EUS database,
      tracking patients and complications for a single endosonographer at a tertiary
      care teaching hospital, data for consecutive patients between August 2003 and
      March 2008 undergoing either EUS-guided CPB or CPN were analyzed for indications,
      methods, and complications. Excellent follow-up data were available for all
      patients. RESULTS: 189 EUS-CPB and 31 EUS-CPN procedures were done in 128 and 30
      patients, respectively (60 men, 98 women). Indications for blockades included
      chronic pancreatitis (122), relapsing pancreatitis with chronic pain (28), upper
      abdominal pain of suspected pancreatic origin (37), and suspected (yet unproven)
      pancreatic cancer with pain (2). Neurolyses were performed for refractory pain
      from cancer (21) or chronic pancreatitis (10). No prophylactic antibiotics were
      administered. Acid suppression was not withheld. Complications were defined as
      procedural side effects treated with anything beyond standard observation. Four
      complications were observed during clinical follow-up (three after CPB, one after
      CPN), giving an overall complication rate of 1.8 % (CPB 1.6 %, CPN 3.2 %).
      Complications included asymptomatic hypotension after neurolysis, retroperitoneal
      abscess after CPB, and severe self-limited postprocedural pain in two patients
      after CPB. CONCLUSIONS: EUS-guided CPB and CPN are reasonably safe procedures
      with tolerable side-effect profiles and low overall complication rates.

PMID- 19588287
TI  - A pilot study of EUS-guided hot saline injection for induction of pancreatic
      tissue necrosis.
AB  - BACKGROUND AND STUDY AIMS: Hot saline may be potentially useful for inducing
      necrosis of pancreatic tissue. However, the local and systemic effects are
      largely unknown. This pilot study aimed to evaluate the feasibility and safety of
      EUS-guided injection of hot saline into the pancreas in the porcine model.
      METHODS: Boiling hot saline was injected into the tail of normal porcine pancreas
      under EUS guidance in six pigs via a transgastric approach. Three pigs were
      killed 4 hours later to study the acute effect of the hot saline injection (acute
      study). The remaining three pigs were killed after 7 days of clinical observation
      (survival study). RESULT: Injection of 5 mL, 2 mL and 1 mL of hot saline produced
      localized necrosis (7 - 10 mm) of pancreatic tissue in the acute study. However,
      there was pooling of hot saline on the surface of the pancreas when 5mL was
      injected. On the basis of the results of the acute study, the volume of hot
      saline injected in the survival study was 1 mL. One milliliter of hot saline
      produced localized or sporadic necrosis of pancreatic tissue without any signs of
      pancreatitis in all three pigs in the survival study; hot saline was observed to
      pool on the pancreatic surface of one pig. There was no histological evidence of
      necrosis in the pancreatic tissue adjacent to the pooled hot saline in either the
      acute or the survival study. CONCLUSION: EUS-guided hot saline injection of
      pancreatic tissue in the porcine model was technically successful and led to
      localized necrosis of pancreatic tissue without any sign of pancreatitis.

PMID- 19588288
TI  - A cost-benefit analysis of endoscopy reporting methods: handwritten, dictated and
      computerized.
AB  - BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy investigations are
      frequently requested by gastroenterologists, general practitioners and other
      physicians. In addition to the classic methods of report writing, several
      electronic endoscopic report systems are currently available. The aim of the
      study was to evaluate the costs of three different ways of producing reports; by
      hand, by dictation, or by computer. METHODS: Three methods of report writing were
      compared, with special attention to costs. The endoscopy process was analyzed,
      from arrival of the patient to sending the report to the referring doctor, and
      including production of endoscopic images or video, logging of used endoscopes
      and their disinfection, and storage costs for endoscopy data. RESULTS: During the
      first 5 years, the mean costs per procedure were Euro 4.78 for handwritten, Euro
      6.39 for dictated and Euro 8.90 for computerized reports. Due to depreciation,
      after this initial period, the respective costs declined to Euro 4.37, Euro 5.20
      and Euro 5.13, respectively. Despite high initial costs, a cost-benefit analysis
      already revealed a financial benefit from a computerized system after 3 years.
      CONCLUSIONS: The electronic production of an endoscopic report turned out to be
      the most expensive way of report writing during the first 5 years, due to high
      initial costs. After 5 years the costs of the different systems were comparable
      with each other. Cost-benefit analysis showed a positive financial benefit for
      computerized reports after 3 years.

PMID- 19588289
TI  - Obesity and the gastroenterologist.

PMID- 19588290
TI  - Biliary cannulation during endoscopic retrograde cholangiopancreatography: core
      technique and recent innovations.
AB  - Despite advances in imaging and device technology over the past decade,
      endoscopic retrograde cholangiopancreatography (ERCP) continues to be one of the
      most technically challenging interventions in endoscopy. The procedure remains
      compounded by two persistent problems: failure of successful biliary cannulation
      and post-ERCP pancreatitis (PEP). When performed outside expert high-volume
      centers, failed biliary cannulation may occur in up to 20 % of cases; repeated
      and prolonged attempts at cannulation increase the risk of pancreatitis, delay
      definitive therapy, and necessitate alternative therapeutic techniques with
      inferior safety profiles . Cannulation technique is believed to be a pivotal
      factor in the genesis of PEP and is obviously important for successful
      cannulation. This review will discuss some recent innovations in cannulation
      technique.

PMID- 19588292
TI  - Role of small-bowel endoscopy in the management of patients with inflammatory
      bowel disease: an international OMED-ECCO consensus.
AB  - Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly
      in the developed countries of the world. Whereas ulcerative colitis is a chronic
      inflammatory condition causing diffuse and continuous mucosal inflammation of the
      colon, Crohn's disease is a heterogeneous entity comprised of several different
      phenotypes, but can affect the entire gastrointestinal tract. A change in
      diagnosis from Crohn's disease to ulcerative colitis during the first year of
      illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD)
      restricted to the colon that cannot be characterized as either ulcerative colitis
      or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and
      both single- and double-balloon-assisted enteroscopy is revolutionizing small
      bowel imaging and has major implications for diagnosis, classification,
      therapeutic decision making and outcomes in the management of IBD. The role of
      these investigations in the diagnosis and management of IBD, however, is unclear.
      This document sets out the current Consensus reached by a group of international
      experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th
      December 2008, organised jointly by the European Crohn's and Colitis Organisation
      (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus
      is grouped into seven sections: definitions and diagnosis; suspected Crohn's
      disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal
      pouch-anal anastomosis [IPAA]); paediatric practice; and complications and
      unresolved questions. Consensus guideline statements are followed by comments on
      the evidence and opinion. Statements are intended to be read in context with
      qualifying comments and not read in isolation.

PMID- 19588293
TI  - UEGW Report 2008: putting endoscopy into perspective.
AB  - The 16th United European Gastroenterology Week (UEGW), which was held in Vienna
      in October 2008, provided the opportunity for those interested in
      gastrointestinal endoscopy to be informed of the experience of colleagues
      throughout the world and to become acquainted with the latest advancements and
      research in the field. Many of these abstracts focused on innovations and new
      techniques, and numerous others concentrated on topics with an impact on everyday
      clinical practice. This report attempts to highlight mostly oral presentations
      but also a few selected poster presentations, and each will be briefly reviewed
      in the light of recent publications in the respective fields of gastrointestinal
      endoscopy.

PMID- 19588294
TI  - Pancreatobiliary maljunction in Western adults.

PMID- 19588295
TI  - Does retroflexion improve adenoma miss rates on the right side of the colon when
      using a pediatric variable-stiffness colonoscope during routine colonoscopy?

PMID- 19588296
TI  - From white points to yellow plaques: magnifying endoscopic features of duodenal
      lymphangiectasia.

PMID- 19588300
TI  - Treatment of acute limb ischemia with focus on endovascular techniques.
AB  - Acute limb ischemia is still the most frequent cause of major limb loss. Timely
      and fast revascularization is the key for limb salvage and patient survival.
      Large randomized trials showed equivalency of surgical and endovascular
      revascularization by means of local lysis with urokinase (TOPAS, STILE). New
      lytic agents and their modified application such as via a pulse spray catheter or
      combined with an ultrasound catheter and the combination with glycoprotein
      IIb/IIIa receptor antagonists have increased the efficacy and speed of
      thrombolysis. Recently, mechanical thrombectomy devices have become more
      widespread because intervention time and bleeding complications can be reduced.
      This review article summarizes the clinical presentation of and the treatment
      options for acute arterial occlusive disease caused either by embolism or local
      thrombosis.

PMID- 19588299
TI  - New developments in tissue engineering of vascular prosthetic grafts.
AB  - Despite remarkable developments in vascular medicine in the last decades and
      intensive research on the improvement of bypass materials, an ideal bypass graft
      comparable to autologous veins or arteries is still not available for peripheral
      vascular and coronary artery bypass grafting. This article reviews established
      bypass materials and provides an overview over interesting new technologies
      particularly those associated with tissue-engineering and those already adopted
      clinically.

PMID- 19588301
TI  - Thromboprophylaxis--key points for the angiologist.
AB  - The expertise and the advice of vascular specialists are important in diagnosis
      and treatment of venous thromboembolism (VTE) and equally important for
      thromboprophylaxis. Thus, vascular specialists are expected to have significant
      knowledge of the exposing and disposing risk factors for VTE. They are also
      expected to be familiar with the risk groups for VTE and the appropriate measures
      for thromboprophylaxis. Because different pharmacological prophylactic strategies
      are available, angiologists must be familiar with the properties, the specific
      labeling and the product information regarding their drugs of choice. Being
      familiar with the pharmacological profile and the potential risk of impaired
      renal function due to drug accumulation is essential for angiologists, both for
      the treatment and prophylaxis of VTE. Appropriate time intervals between
      application of thromboprophylaxis and spinal or epidural anaesthesia should be
      observed. This is also important for the recently available oral thrombin- and
      factor Xa-inhibitors. Presently available data do not support routine
      pharmacological prophylaxis for patients in the low VTE-risk group. Rather,
      individual risk benefit assessment is required in these patients. Patients with
      moderate or high VTE risk should receive pharmacological thromboprophylaxis.
      There is clear evidence and recommendation for prolonged administration of
      thromboprophylaxis over a 4-week period in patients following major orthopaedic
      surgery, such as hip replacement, hip fracture and in cancer surgery patients.
      Pulmonary embolism (PE) remains the most common preventable cause of death among
      hospitalized patients. Therefore, angiologists have a central role in ensuring
      adequate and consistent implementation of thromboprophylaxis, which is the number
      one strategy to improve patient safety in hospitals.

PMID- 19588302
TI  - Common femoral artery intima-media thickness as marker for cardiovascular disease
      in asymptomatic adults.
AB  - BACKGROUND: The common carotid intima-media thickness (IMT) is considered as a
      marker of cardiovascular disease, while the value of the common femoral IMT is
      not well defined. The aim of the present study was to investigate the value of
      common femoral IMT alone or in combination with the common carotid IMT as a
      marker of cardiovascular disease in asymptomatic adults. PATIENTS AND METHODS:
      Eighty-three individuals with no history of cardiovascular disease were subjected
      to IMT measurement of both common carotid and common femoral arteries with high
      resolution ultrasonography. The Framingham Heart Study (FHS) risk score was
      calculated for each subject (according to gender) and was correlated with the
      carotid IMT, femoral IMT, and the combined IMT measured at both arterial sites.
      RESULTS: The carotid and femoral IMT separately and in combination were found to
      be correlated with the FHS risk score, calculated based on either the total
      cholesterol or low density lipoprotein plasma levels (carotid IMT: r = 0.28, p =
      0.035, and r = 0.35, p = 0.007, respectively, femoral IMT: r = 0.38, p = 0.003,
      and r = 0.43, p = 0.001, respectively, carotid-femoral IMT: r = 0.37, p = 0.005,
      and r = 0.46, p = 0.0001, respectively). In addition, femoral IMT was found to be
      correlated with the carotid IMT (r = 0.41, p = 0.001). CONCLUSIONS: Common
      carotid and common femoral IMT showed similar correlation with the FHS risk
      score. Additionally, the combination of IMT from both arterial sites was found to
      have similar correlation with the FHS risk score to carotid IMT alone.

PMID- 19588303
TI  - The influence of atorvastatin on walking performance in peripheral arterial
      disease.
AB  - BACKGROUND: Recently it has been shown that statins can improve walking distance
      in patients with peripheral arterial disease. We examined whether statins used in
      moderate dosages with the aim of reaching the target levels for
      hypercholesterolemia could improve walking performance in patients with
      peripheral arterial disease. PATIENTS AND METHODS: 37 patients with
      hypercholesterolemia (LDL cholesterol = 3.46 +/- 0.13 mmol/l), who had previously
      not been treated by statins, were randomized in a double-blind study to a group
      receiving either atorvastatin at 20 mg/day (N = 20) or placebo (N = 17). All
      patients had stable intermittent claudication (Fontaine class IIa or IIb). At
      baseline, after one and three months the pain-free walking distance was measured
      in all patients. RESULTS: After 3 months patients in the treated group had
      reached target cholesterol values (LDL cholesterol = 2,34 +/- 0.9 mmol/l),
      whereas no significant change in lipids was observed in the control group. The
      ankle-brachial pressure index (ABPI) did not change significantly in either
      group. After 3 months the pain-free walking distance was increased significantly
      (p < 0.001), but similarly in both groups (at entry: 56 (53-108) m vs 53 (53-106)
      m; after 3 months: 79 (53-108) m vs 106 (66-159) m, for the treated and placebo
      group, respectively). Therefore this effect had to be attributed to regular
      exercise and not to statin use. CONCLUSIONS: Our results show that routine
      treatment with statin (atorvastatin 20 mg/day), which is effective in reducing
      the level of cholesterol, does not produce an improvement in walking performance
      in patients with peripheral arterial disease.

PMID- 19588304
TI  - Asymptomatic venous thrombosis in cancer patients--a problem often overlooked.
      Results of a retrospective and prospective study.
AB  - BACKGROUND: Venous thrombosis with and without pulmonary embolism is a frequent
      complication of malignancies and second among the causes of death in tumour
      patients. Its incidence is reported to be 10 to 15%. Since for methodological
      reasons, this rate can be assumed to be too low and to disregard asymptomatic
      venous thrombosis, a combined retrospective and prospective study was performed
      to examine the actual frequency of venous thrombosis in tumour patients. PATIENTS
      AND METHODS: The histories of 409 patients (175 women, 234 men, mean age 69 years
      [19 to 96 years]) with different tumours, consecutively enrolled in the order of
      their altogether 426 inpatient treatments, were checked in retrospect for the
      frequency of venous thrombosis and pulmonary embolism. Subsequently, 97 tumour
      inpatients (36 women, 61 men, mean age 70 years [42 to 90 years]) were
      systematically screened, by means of duplex sonography and/or venography, for
      venous thromboses in the veins of the pelvis and both legs. RESULTS: In the
      retrospective analysis, where no systematic screening for thromboses was
      performed and only symptomatic thrombosis was recorded, venous thrombosis was
      found in 6.6% of all tumour patients, whereas in the prospective examination with
      systematic duplex sonography and / or venography of all patients, the percentage
      was 33%. In the prospective study, 31.3% of venous thromboses were symptomatic
      and 68.7% asymptomatic. In 39.3% of the cases in the retrospective analysis and
      25% in the prospective analysis, venous thrombosis occurred during chemotherapy,
      surgery or radiation therapy. Venous thrombosis was most often seen in
      metastasizing tumours and in colorectal carcinoma (40%), haematological system
      diseases (28.6%), gastric cancer (30%), bronchial, pancreas and ovarian carcinoma
      (28.6%), and carcinoma of the prostate (16.7%). CONCLUSION: Regular screening for
      thrombosis is indicated even in asymptomatic tumour patients because asymptomatic
      venous thrombosis is frequent, can lead to pulmonary embolism and has to be
      treated like symptomatic venous thrombosis. This is particularly true for
      metastasization during chemotherapy, surgical interventions, or radiation.

PMID- 19588305
TI  - Tumors associated with superficial thrombophlebitis.
AB  - BACKGROUND: To assess the incidence of malignant tumors in patients with
      thrombophlebitis of the leg with regard to potential early tumor detection.
      PATIENTS AND METHODS: 140 consecutive patients were enrolled over a period of
      over 9 years in a retrospective follow-up study based on the electronic patient
      record. RESULTS: There were 18 patients (12.9%) suffering from thrombophlebitis
      in association with a malignant tumor: breast cancer in seven patients, colon
      carcinoma and haematologic cancer in four, skin cancer in three patients and one
      case each of oesophageal, prostatic, kidney and neck cancer . In two patients
      thrombophlebitis preceded the diagnosis of the malignancy. Superficial
      thrombophlebitis may have been associated in four cases (2.9%) with a benign
      tumor. CONCLUSIONS: Breast, colonic, haematological and skin cancer were mainly
      associated with superficial thrombophlebitis in our patients. In case of a
      thrombophlebitis without a known malignancy a thorough clinical examination with
      special regard to skin, breast and abdomen is mandatory.

PMID- 19588306
TI  - Severity of chronic venous disorders and its relationship to the calf muscle
      pump.
AB  - BACKGROUND: To investigate the relationship between the calf muscle pump and the
      clinical severity of chronic venous disorders (CVD) and of venous function
      parameters. PATIENTS AND METHODS: 84 limbs in 44 patients underwent duplex scan
      and digital photoplethysmography (DPPG), the range of ankle movement was measured
      by digital goniometry and strength of calf muscles was determined by dynamometry.
      Limbs were allocated on the basis of clinical signs of CVD (according to the CEAP
      classification) into 4 groups: controls (no signs and symptoms of CVD): 34 limbs,
      C1/2: 24 limbs, C3/4: 16 limbs, C6: 10 limbs. RESULTS: A higher degree in
      clinical severity of CVD was related to shorter venous refilltime (VRT) and lower
      venous pump power (VPP) measured by DPPG. The strength of dorsiflexion was
      significantly reduced in group C6 compared to controls. There was a positive
      correlation between measurements of DPPG and the strength of dorsiflexion and
      also with total strength (p < 0.05). In limbs with pathological reflux (> 1 s)
      the strength of dorsiflexion, range of ankle plantarflexion movement and total
      range of ankle movement were significantly reduced compared to those without
      pathological reflux (p < 0,05). Strength of plantarflexion was significantly
      reduced in group C1/2 compared to control group (p < 0,05). CONCLUSIONS: Strength
      of dorsiflexion seems to be the main driving factor of normal venous flow and
      range of ankle movement is impaired in patients with pathological venous reflux.
      Further prospective studies should clarify if additional strengthening of ankle
      dorsiflexors should be included in well established venous training programs.

PMID- 19588307
TI  - Traumatic vertebral artery aneurysm following blunt suboccipital trauma.
AB  - Traumatic vertebral artery (VA) injury has been neglected and mistaken to be
      innocuous. Herein, we present a rare case with a as subarachnoid hemorrhage (SAH)
      following blunt suboccipital trauma. Initially, it was mistaken as a saccular
      aneurysm and was just coincident with traumatic SAH. Surgical clipping was
      performed by our senior neurosurgeon and looked secure. But massive bleeding
      occurred before complete closure of the dura wound. Opening the wound again,
      blood gushed out from the junction of the aneurysm and the parent artery. Because
      preoperative angiography evaluation had revealed good collateral flow from the
      contralateral VA, the involved segment of VA was trapped. The patient recovered
      well with uneventful course. Blunt suboccipital trauma may result in traumatic VA
      injury which may cause catastrophic complications if neglected. The incidence,
      risk factors, the pathophysiology of traumatic VA aneurysm, and the treatments
      are reviewed.

PMID- 19588308
TI  - A dreadful sign of aortic dissection: aortic intimo-intimal intussusception with
      prominent intimal flap prolapsing into the left ventricular apex.
AB  - Intimo-intimal intussusception is an unusual clinical form of aortic dissection
      resulting from circumferential detachment of the intima. Clinical presentation
      varies according to the level of detached intima in the aorta. We present a case
      of acute type A dissection with prominent prolapse of the circumferential
      detachment intimal flap into the left ventricular cavity extended to the apex.

PMID- 19588310
TI  - Giant arteriovenous fistula after implantation of a percutaneous left ventricular
      assist device.
AB  - INTRODUCTION: Percutaneous left ventricular assist devices are an important tool
      in the management of patients with severe cardiogenic shock. Limited experiences
      concerning vascular complications after long term implantation of these devices
      exist. We report on a large arteriovenous fistula after placement of a left
      ventricular assist device, which has not been described in the literature. The
      arteriovenous fistula was of clinical relevance because it represented a
      supplementary cardiac burden in a patient with impaired left ventricular function
      after a severe myocardial infarction.

PMID- 19588309
TI  - Successful revascularisation of a thrombosed renal artery aneurysm in a young man
      with solitary kidney and history of severe hypertension.
AB  - Case report of a 18-year-old patient with long lasting hypertension, who
      developed acute renal failure, in course of an antihypertensive therapy
      modification, backgrounded by undiagnosed aneurysm of the solitary kidney renal
      artery. The acute renal function decrease was caused by single dose of ACE
      inhibitor causing an equivalent drop in serum ACE activity. Aneurysm excision
      followed by implantation of a venous bypass normalized restored renal function
      and blood pressure for over 24 months of observation.

PMID- 19588311
TI  - Lymphoplasmacytic lymphoma with Waldenstrom's macroglobulinemia as a reason for
      peripheral arterial perfusion disorders.
AB  - Peripheral arterial perfusion disorders are often caused by embolism and
      thrombosis induced by diseases of the cardiovascular system. We report about a
      case of a 42-year-old female with peripheral arterial perfusion disturbances of
      the digital arteries caused by Waldenstrom s disease due to high plasma
      viscosity. Our patient presented with elevated plasma viscosity (1.34 mPA) and
      therefore plasmapheresis was necessary. Plasma separation is the most effective
      acute treatment for symptomatic hyperviscosity syndrome. In a second step
      patients with clinical symptoms of M. Waldenstrom have to be treated by
      chemotherapy.

PMID- 19588312
TI  - Ischemic colitis after lithotripsy for nephrolithiasis: a hypothetical
      explanation for an association.

PMID- 19588315
TI  - WITHDRAWN: Active versus expectant management in the third stage of labour.
AB  - BACKGROUND: Expectant management of the third stage of labour involves allowing
      the placenta to deliver spontaneously or aiding by gravity or nipple stimulation.
      Active management involves administration of a prophylactic oxytocic before
      delivery of the placenta, and usually early cord clamping and cutting, and
      controlled cord traction of the umbilical cord. OBJECTIVES: The objective of this
      review was to assess the effects of active versus expectant management on blood
      loss, post partum haemorrhage and other maternal and perinatal complications of
      the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials
      comparing active and expectant management of the third stage of labour in women
      who were expecting a vaginal delivery. DATA COLLECTION AND ANALYSIS: Trial
      quality was assessed and data were extracted independently by the reviewers. MAIN
      RESULTS: Five studies were included. Four of the trials were of good quality.
      Compared to expectant management, active management (in the setting of a
      maternity hospital) was associated with the following reduced risks: maternal
      blood loss (weighted mean difference -79.33 millilitres, 95% confidence interval 
      94.29 to -64.37); post partum haemorrhage of more than 500 millilitres (relative
      risk 0.38, 95% confidence interval 0.32 to 0.46); prolonged third stage of labour
      (weighted mean difference -9.77 minutes, 95% confidence interval -10.00 to 
      9.53). Active management was associated with an increased risk of maternal nausea
      (relative risk 1.83, 95% confidence interval 1.51 to 2.23), vomiting and raised
      blood pressure (probably due to the use of ergometrine). No advantages or
      disadvantages were apparent for the baby. AUTHORS' CONCLUSIONS: Routine 'active
      management' is superior to 'expectant management' in terms of blood loss, post
      partum haemorrhage and other serious complications of the third stage of labour.
      Active management is, however, associated with an increased risk of unpleasant
      side effects (eg nausea and vomiting), and hypertension, where ergometrine is
      used. Active management should be the routine management of choice for women
      expecting to deliver a baby by vaginal delivery in a maternity hospital. The
      implications are less clear for other settings including domiciliary practice (in
      developing and industrialised countries).

PMID- 19588317
TI  - Elective high frequency oscillatory ventilation versus conventional ventilation
      for acute pulmonary dysfunction in preterm infants.
AB  - BACKGROUND: Respiratory failure due to lung immaturity is a major cause of
      mortality in preterm infants. Although the use of intermittent positive pressure
      ventilation (IPPV) in neonates with respiratory failure saves lives, its use is
      associated with lung injury and chronic lung disease (CLD). A newer form of
      ventilation called high frequency oscillatory ventilation (HFOV) has been shown
      to result in less lung injury in experimental studies. OBJECTIVES: The objective
      of this review is to determine the effect of the elective use of high frequency
      oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) on
      the incidence of chronic lung disease, mortality and other complications
      associated with prematurity and assisted ventilation in preterm infants who are
      mechanically ventilated for respiratory distress syndrome (RDS). SEARCH STRATEGY:
      Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE,
      previous reviews including cross references, abstracts, conferences and symposia
      proceedings, expert informants, journal hand searching by the Cochrane
      Collaboration, mainly in the English language. The search was updated in January
      2009. SELECTION CRITERIA: Randomised controlled trials comparing HFOV and CV in
      preterm or low birth weight infants with pulmonary dysfunction, mainly due to
      RDS, who required assisted ventilation. Randomisation and commencement of
      treatment needed to be as soon as possible after the start of CV and usually in
      the first 12 hours of life. DATA COLLECTION AND ANALYSIS: The methodological
      quality of each trial was independently reviewed by the various authors. The
      standard effect measures are relative risk (RR) and risk difference (RD). From
      1/RD the number needed to treat (NNT) to produce one outcome were calculated. For
      all measures of effect, 95% confidence intervals were used. In subgroup analyses
      the 99% CIs are also given for summary RRs in the text. Meta-analysis was
      performed using a fixed effects model. Where heterogeneity was over 50%, the
      random effects RR is also given. MAIN RESULTS: Seventeen eligible studies of
      3,652 infants were included. Meta-analysis comparing HFOV with CV revealed no
      evidence of effect on mortality at 28 - 30 days of age or at approximately term
      equivalent age. These results were consistent across studies and in subgroup
      analyses. The effect of HFOV on CLD in survivors at term equivalent gestational
      age was inconsistent across studies and the reduction was of borderline
      significance overall. The effect was similar in trials with a high lung volume
      strategy for HFOV targeting at very low FiO(2) and trials with a high lung volume
      strategy with somewhat higher or unspecified target FiO(2). Subgroups of trials
      showed a significant reduction in CLD with HFOV when no surfactant was used, when
      piston oscillators were used for HFOV, when lung protective strategies for CV
      were not used, when randomisation occurred at two to six hours of age, and when
      inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta-analysis of
      all trials, pulmonary air leaks occurred more frequently in the HFOV group.In
      some studies, short-term neurological morbidity with HFOV was found, but this
      effect was not statistically significant overall. The subgroup of two trials not
      using a high volume strategy with HFOV found increased rates of Grade 3 or 4
      intraventricular haemorrhage and of periventricular leukomalacia. An adverse
      effect of HFOV on long-term neurodevelopment was found in one large trial but not
      in the five other trials that reported this outcome. The rate of retinopathy of
      prematurity is reduced overall in the HFOV group. AUTHORS' CONCLUSIONS: There is
      no clear evidence that elective HFOV offers important advantages over CV when
      used as the initial ventilation strategy to treat preterm infants with acute
      pulmonary dysfunction. There may be a small reduction in the rate of CLD with
      HFOV use, but the evidence is weakened by the inconsistency of this effect across
      trials and the overall borderline significance. Future trials on elective HFOV
      should target those infants who are at most risk of CLD (extremely preterm
      infants), compare different strategies for generating HFOV and CV, and report
      important long-term neurodevelopmental outcomes.

PMID- 19588316
TI  - Interprofessional collaboration: effects of practice-based interventions on
      professional practice and healthcare outcomes.
AB  - BACKGROUND: Poor interprofessional collaboration (IPC) can negatively affect the
      delivery of health services and patient care. Interventions that address IPC
      problems have the potential to improve professional practice and healthcare
      outcomes. OBJECTIVES: To assess the impact of practice-based interventions
      designed to change IPC, compared to no intervention or to an alternate
      intervention, on one or more of the following primary outcomes: patient
      satisfaction and/or the effectiveness and efficiency of the health care provided.
      Secondary outcomes include the degree of IPC achieved. SEARCH STRATEGY: We
      searched the Cochrane Effective Practice and Organisation of Care Group
      Specialised Register (2000-2007), MEDLINE (1950-2007) and CINAHL (1982-2007). We
      also handsearched the Journal of Interprofessional Care (1999 to 2007) and
      reference lists of the five included studies. SELECTION CRITERIA: Randomised
      controlled trials of practice-based IPC interventions that reported changes in
      objectively-measured or self-reported (by use of a validated instrument)
      patient/client outcomes and/or health status outcomes and/or healthcare process
      outcomes and/or measures of IPC. DATA COLLECTION AND ANALYSIS: At least two of
      the three reviewers independently assessed the eligibility of each potentially
      relevant study. One author extracted data from and assessed risk of bias of
      included studies, consulting with the other authors when necessary. A meta
      analysis of study outcomes was not possible given the small number of included
      studies and their heterogeneity in relation to clinical settings, interventions
      and outcome measures. Consequently, we summarised the study data and presented
      the results in a narrative format. MAIN RESULTS: Five studies met the inclusion
      criteria; two studies examined interprofessional rounds, two studies examined
      interprofessional meetings, and one study examined externally facilitated
      interprofessional audit. One study on daily interdisciplinary rounds in inpatient
      medical wards at an acute care hospital showed a positive impact on length of
      stay and total charges, but another study on daily interdisciplinary rounds in a
      community hospital telemetry ward found no impact on length of stay. Monthly
      multidisciplinary team meetings improved prescribing of psychotropic drugs in
      nursing homes. Videoconferencing compared to audioconferencing multidisciplinary
      case conferences showed mixed results; there was a decreased number of case
      conferences per patient and shorter length of treatment, but no differences in
      occasions of service or the length of the conference. There was also no
      difference between the groups in the number of communications between health
      professionals recorded in the notes. Multidisciplinary meetings with an external
      facilitator, who used strategies to encourage collaborative working, was
      associated with increased audit activity and reported improvements to care.
      AUTHORS' CONCLUSIONS: In this updated review, we found five studies (four new
      studies) that met the inclusion criteria. The review suggests that practice-based
      IPC interventions can improve healthcare processes and outcomes, but due to the
      limitations in terms of the small number of studies, sample sizes, problems with
      conceptualising and measuring collaboration, and heterogeneity of interventions
      and settings, it is difficult to draw generalisable inferences about the key
      elements of IPC and its effectiveness. More rigorous, cluster randomised studies
      with an explicit focus on IPC and its measurement, are needed to provide better
      evidence of the impact of practice-based IPC interventions on professional
      practice and healthcare outcomes. These studies should include qualitative
      methods to provide insight into how the interventions affect collaboration and
      how improved collaboration contributes to changes in outcomes.

PMID- 19588318
TI  - Early trophic feeding for very low birth weight infants.
AB  - BACKGROUND: The introduction of enteral feeds for very low birth weight (VLBW)
      infants is often delayed due to concern that early introduction may not be
      tolerated and may increase the risk of necrotising enterocolitis. However,
      enteral fasting may diminish the functional adaptation of the immature
      gastrointestinal tract and prolong the need for parenteral nutrition with its
      attendant infectious and metabolic risks. Early trophic feeding, giving infants
      very small volumes of milk during the first week after birth, may promote
      intestinal maturation, enhance feeding tolerance and decrease time to reach full
      enteral feeding independently of parenteral nutrition. OBJECTIVES: To determine
      the effect of early trophic feeding versus enteral fasting on feed tolerance,
      growth, and the incidence of necrotising enterocolitis, mortality and other
      morbidities in VLBW infants. SEARCH STRATEGY: The standard search strategy of the
      Cochrane Neonatal Group was used. Searches were made of the Cochrane Central
      Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2009),
      MEDLINE (1966 - February 2009), EMBASE (1980 - February 2009), CINAHL (1982 -
      February 2009), conference proceedings, and previous reviews. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials that assessed the effects of
      early trophic feeding (milk volumes up to 24 ml/kg/day introduced before 96 hours
      postnatal age and continued until at least one week after birth) versus a
      comparable period of enteral fasting in VLBW infants. DATA COLLECTION AND
      ANALYSIS: The standard methods of the Cochrane Neonatal Group were used, with
      separate evaluation of trial quality and data extraction by two review authors.
      Data were synthesised using a fixed effects model and reported using typical
      relative risk, typical risk difference and weighted mean difference. MAIN
      RESULTS: Nine trials, in which a total of 754 VLBW infants participated, were
      eligible for inclusion. These trials did not provide any evidence that early
      trophic feeding affected feed tolerance or growth rates in VLBW infants. Meta
      analysis did not detect a statistically significant effect on the incidence of
      necrotising enterocolitis: typical relative risk 1.07 (95% confidence interval
      0.67, 1.70); typical risk difference 0.01 (95% confidence interval -0.04, 0.05).
      AUTHORS' CONCLUSIONS: The available data cannot exclude important beneficial or
      harmful effects and are insufficient to inform clinical practice. Further large
      pragmatic randomised controlled trials are needed to determine how early trophic
      feeding compared with enteral fasting affects important clinical outcomes in VLBW
      infants.

PMID- 19588319
TI  - Interventions for isolated diaphyseal fractures of the ulna in adults.
AB  - BACKGROUND: Isolated fractures of the shaft of the ulna, which are often
      sustained when the forearm is raised to shield against a blow, are generally
      treated on an outpatient basis. OBJECTIVES: To assess the effects of various
      forms of treatment for isolated fractures of the ulnar shaft in adults. SEARCH
      STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group
      Specialised Register (December 2008), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library 2008, Issue 4), MEDLINE (1966 to November week 3
      2008), EMBASE (1981 to week 52 2008), CINAHL (1982 to December week 2 2008),
      various trial registers, various conference proceedings and bibliographies of
      relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised trials of
      conservative and surgical treatment of isolated fractures of the ulnar shaft in
      adults. Excluded were fractures of the proximal ulna and Monteggia fracture
      dislocations. DATA COLLECTION AND ANALYSIS: We performed independent assessment
      of risk of bias and data extraction. We contacted trialists for more information.
      There was no pooling of data. MAIN RESULTS: Four trials, involving a total of 237
      participants, were included. All four trials were methodologically flawed and
      potentially biased.Three trials tested conservative treatment interventions. One
      trial, which compared short arm (below elbow) pre-fabricated functional braces
      with long arm (elbow included) plaster casts, found there was no significant
      difference in the time it took for fracture union. Patient satisfaction and
      return to work during treatment were significantly better in the brace group. The
      other two trials, both quasi-randomised, had three treatment groups. One trial
      compared Ace Wrap elastic bandage versus short arm plaster cast versus long arm
      plaster cast. The large loss to follow-up in this trial makes any data analysis
      tentative. However, the need for replacement of the Ace wrap by other methods due
      to pain indicates the potential for a serious problem with this intervention. The
      other trial, which compared immediate mobilisation versus short arm plaster cast
      versus long arm plaster cast for minimally displaced fractures, found no
      significant differences in outcome between these three interventions.The fourth
      trial, which compared two types of plates for surgical fixation, found no
      significant differences in functional or anatomical outcomes nor complications
      between the two groups. AUTHORS' CONCLUSIONS: There is insufficient evidence from
      randomised trials to determine which method of treatment is the most appropriate
      for isolated fractures of the ulnar shaft in adults. Well designed and reported
      randomised trials of current forms of conservative treatment are recommended.

PMID- 19588320
TI  - Post-operative radiotherapy for ductal carcinoma in situ of the breast.
AB  - BACKGROUND: The addition of radiotherapy (RT) following breast conserving surgery
      (BCS) was first shown to reduce the risk of ipsilateral recurrence in the
      treatment of invasive breast cancer. Ductal carcinoma in situ (DCIS) is a pre
      invasive lesion. Recurrence of ipsilateral disease following BCS can be either
      DCIS or invasive breast cancer. Randomised controlled trials (RCTs) have shown
      that RT can reduce the risk of recurrence, but assessment of potential long-term
      complications from addition of RT following BSC for DCIS has not been reported
      for women participating in RCTs. OBJECTIVES: To summarise the data from RCTs
      testing the addition of RT to BCS for treatment of DCIS to determine the balance
      between the benefits and harms. SEARCH STRATEGY: We searched the Cochrane Breast
      Cancer Group Specialised Register (January 2008), Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1), MEDLINE
      (February 2008), and EMBASE (February 2008). Reference lists of articles and
      handsearching of ASCO (2007), ESMO (2002 to 2007), and St Gallen (2005 to 2007)
      conferences were performed. SELECTION CRITERIA: RCTs of breast conserving surgery
      with and without radiotherapy in women at first diagnosis of pure ductal
      carcinoma in situ (no invasive disease present). DATA COLLECTION AND ANALYSIS:
      Two authors independently assessed each potentially eligible trial for inclusion
      and its quality. Two authors also independently extracted data from published
      Kaplan-Meier analysis (survival curves) and reported summary statistics. Data
      were extracted and pooled for four trials. Data for planned subgroups were
      extracted and pooled for analysis.There were insufficient data to pool for long
      term toxicity from radiotherapy. MAIN RESULTS: Four RCTs involving 3925 women
      were identified and included in this review. All were high quality with minimal
      risk of bias. Three trials compared the addition of RT to BCS. One trial was a
      two by two factorial design comparing the use of RT and tamoxifen, each
      separately or together, in which participants were randomised in at least one
      arm. Analysis confirmed a statistically significant benefit from the addition of
      radiotherapy on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI
      0.41 to 0.59, P < 0.00001) and ipsilateral DCIS recurrence (HR 0.64; 95% CI 0.41
      to 1.01, P = 0.05). Pooled analysis for invasive recurrence did not reach
      statistical significance. All the subgroups analysed benefited from addition of
      radiotherapy. No significant long-term toxicity from radiotherapy was found. No
      information about short-term toxicity from radiotherapy or quality of life data
      were reported. AUTHORS' CONCLUSIONS: This review confirms the benefit of adding
      radiotherapy to breast conserving surgery for the treatment of all women
      diagnosed with DCIS. No long-term toxicity from use of radiotherapy was
      identified.

PMID- 19588321
TI  - Corticosteroids for the prevention and treatment of post-extubation stridor in
      neonates, children and adults.
AB  - BACKGROUND: Post-extubation stridor may prolong length of stay in the intensive
      care unit, particularly if airway obstruction is severe and re-intubation proves
      necessary. Some clinicians use corticosteroids to prevent or treat post
      extubation stridor, but corticosteroids may be associated with adverse effects
      ranging from hypertension to hyperglycaemia, so a systematic assessment of the
      efficacy of this therapy is indicated. OBJECTIVES: To determine whether
      corticosteroids are effective in preventing or treating post-extubation stridor
      in critically ill infants, children, or adults. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and
      reference lists of articles. The most recent searches were conducted in January
      2009. SELECTION CRITERIA: Randomized controlled trials comparing administration
      of corticosteroids by any route with placebo in infants, children, or adults
      receiving mechanical ventilation via an endotracheal tube in an intensive care
      unit. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed
      trial quality and extracted data. MAIN RESULTS: Eleven trials involving 2301
      people were included: six in adults, two in neonates, three in children. All but
      one examined use of steroids for the prevention of post-extubation stridor; the
      remaining one concerned treatment of existing post-extubation stridor in
      children. Patients were drawn from heterogeneous medical/surgical populations.
      Dexamethasone given intravenously at least once prior to extubation was the most
      common steroid regimen utilized (uniformly in neonates and children). In neonates
      the two studies found heterogeneous results, with no overall statistically
      significant reduction in post extubation stridor (RR 0.42; 95% CI 0.07 to 2.32).
      One of these studies was on high-risk patients treated with multiple doses of
      steroids around the time of extubation, and this study showed a significant
      reduction in stridor. In children, the two studies were clinically heterogeneous.
      One study included children with underlying airway abnormalities and the other
      excluded this group. Prophylactic corticosteroids tended to reduce reintubation
      and significantly reduced post-extubation stridor in the study that included
      children with underlying airway abnormalities (N = 62) but not in the study that
      excluded these children (N = 153). In six adult studies (total N = 1953), the use
      of prophylactic corticosteroid administration did not significantly reduce the
      risk of re-intubation (RR 0.48; 95% CI 0.19 to 1.22). While there was a
      significant reduction in the incidence of post extubation stridor (RR 0.47; 95%
      CI 0.22 to 0.99), there was significant heterogeneity (I(2)=81%, X(2)=26.36,
      df=5, p<0.0001). Subgroup analysis revealed that post extubation stridor could be
      reduced in adults with a high likelihood of post extubation stridor when
      corticosteroids were administered as multiple doses begun 12-24 hours prior to
      extubation compared to single doses closer to extubation; the test for
      interaction for multiple versus single doses indicated RRR 0.22 (95% CI 0.10 to
      0.47) for stridor with multiple doses. Side effects were uncommon and could not
      be aggregated. AUTHORS' CONCLUSIONS: Using corticosteroids to prevent (or treat)
      stridor after extubation has not proven effective for neonates or children.
      However, given the consistent trends towards benefit, this intervention does
      merit further study, particularly for high risk children or neonates. In adults,
      multiple doses of corticosteroids begun 12-24 hours prior to extubation do appear
      beneficial for patients with a high likelihood of post extubation stridor.

PMID- 19588324
TI  - WITHDRAWN: Antibiotics for preventing leptospirosis.
AB  - BACKGROUND: Leptospirosis is an infectious disease transmitted by animals. Death
      occurs in about five per cent of the patients. In clinical practice, doxycycline
      is widely used for prevention. OBJECTIVES: To evaluate the effectiveness and
      safety of any antibiotic regimen versus placebo or other antibiotic regimens in
      the prophylaxis of leptospirosis. SEARCH STRATEGY: The sources used were: EMBASE,
      LILACS, MEDLINE, SCISEARCH, The Cochrane Controlled Trials Register, The Cochrane
      Hepato-Biliary Group Controlled Trials Register, bibliographies of published
      papers, and personal communication with authors. There were no language or date
      restrictions in any of the searches. SELECTION CRITERIA:  STUDIES: All randomised
      clinical trials in which antibiotics were used as prophylactic regimen for
      leptospirosis. PARTICIPANTS: People potentially exposed to leptospirosis, such as
      people in endemic areas during the rainy season, health professionals and other
      professionals with high risk of infection. INTERVENTION: Any antibiotic regimen
      compared with a control group (placebo or another antibiotic regimen). OUTCOMES:
      Infection (primary outcome) and adverse events (secondary outcome). DATA
      COLLECTION AND ANALYSIS: Data were independently extracted and methodological
      quality of each trial was assessed by two reviewers as well as cross-checked.
      Details of the randomisation (generation and concealment), blinding, and the
      number of patients lost to follow-up were recorded. The results of each trial
      were summarised on an intention-to-treat basis in 2 x 2 tables for each outcome.
      MAIN RESULTS: Two trials comparing doxycycline with placebo met the inclusion
      criteria. We did not find trials comparing doxycycline versus other antibiotics,
      or other antibiotics versus placebo. One of the trials had excellent
      methodological quality. In the other trial, the allocation concealment process,
      generation of allocation sequence, and blinding methods were not described.Of the
      1022 participants enrolled, 509 were treated with doxycycline and 513 with
      placebo. Of these, 940 participants were soldiers included in one trial. The
      patients assigned to the antibiotics group compared with the ones assigned to the
      placebo group showed: Symptomatic, verified leptospirosis: 0.6% (3/509) versus
      4.9% (25/ 513); risk difference (random effects model) -4.1%, 95% confidence
      interval -5.9% to -2.3%. Number needed-to-treat 24 (95% confidence interval 17 to
      43). Adverse effects: 3% (13/469 participants) versus 0.2% (1/471 participants);
      random effects model 2.6%, 95% confidence interval 1.0% to 4.1%. Number needed-to
      harm 39 (95% confidence interval 25 to 100). AUTHORS' CONCLUSIONS: Prophylaxis of
      leptospirosis may be achieved by administration of doxycycline to soldiers
      training in endemic areas with a high risk of exposure to leptospirosis. Whether
      these findings apply to other scenarios or not remains to be proven.

PMID- 19588325
TI  - Decision aids for people facing health treatment or screening decisions.
AB  - BACKGROUND: Decision aids prepare people to participate in 'close call' decisions
      that involve weighing benefits, harms, and scientific uncertainty. OBJECTIVES: To
      conduct a systematic review of randomised controlled trials (RCTs) evaluating the
      efficacy of decision aids for people facing difficult treatment or screening
      decisions. SEARCH STRATEGY: We searched MEDLINE (Ovid) (1966 to July 2006);
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library;
      2006, Issue 2); CINAHL (Ovid) (1982 to July 2006); EMBASE (Ovid) (1980 to July
      2006); and PsycINFO (Ovid) (1806 to July 2006). We contacted researchers active
      in the field up to December 2006. There were no language restrictions. SELECTION
      CRITERIA: We included published RCTs of interventions designed to aid patients'
      decision making by providing information about treatment or screening options and
      their associated outcomes, compared to no intervention, usual care, and alternate
      interventions. We excluded studies in which participants were not making an
      active treatment or screening decision, or if the study's intervention was not
      available to determine that it met the minimum criteria to qualify as a patient
      decision aid. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened abstracts for inclusion, and extracted data from included studies using
      standardized forms. The primary outcomes focused on the effectiveness criteria of
      the International Patient Decision Aid Standards (IPDAS) Collaboration:
      attributes of the decision and attributes of the decision process. We considered
      other behavioural, health, and health system effects as secondary outcomes. We
      pooled results of RCTs using mean differences (MD) and relative risks (RR) using
      a random effects model. MAIN RESULTS: This update added 25 new RCTs, bringing the
      total to 55. Thirty-eight (69%) used at least one measure that mapped onto an
      IPDAS effectiveness criterion: decision attributes: knowledge scores (27 trials);
      accurate risk perceptions (11 trials); and value congruence with chosen option (4
      trials); and decision process attributes: feeling informed (15 trials) and
      feeling clear about values (13 trials).This review confirmed the following
      findings from the previous (2003) review. Decision aids performed better than
      usual care interventions in terms of: a) greater knowledge (MD 15.2 out of 100;
      95% CI 11.7 to 18.7); b) lower decisional conflict related to feeling uninformed
      (MD -8.3 of 100; 95% CI -11.9 to -4.8); c) lower decisional conflict related to
      feeling unclear about personal values (MD -6.4; 95% CI -10.0 to -2.7); d) reduced
      the proportion of people who were passive in decision making (RR 0.6; 95% CI 0.5
      to 0.8); and e) reduced proportion of people who remained undecided post
      intervention (RR 0.5; 95% CI 0.3 to 0.8). When simpler decision aids were
      compared to more detailed decision aids, the relative improvement was significant
      in knowledge (MD 4.6 out of 100; 95% CI 3.0 to 6.2) and there was some evidence
      of greater agreement between values and choice.In this review, we were able to
      explore the use of probabilities in decision aids. Exposure to a decision aid
      with probabilities resulted in a higher proportion of people with accurate risk
      perceptions (RR 1.6; 95% CI 1.4 to 1.9). The effect was stronger when
      probabilities were measured quantitatively (RR 1.8; 95% CI 1.4 to 2.3) versus
      qualitatively (RR 1.3; 95% CI 1.1 to 1.5).As in the previous review, exposure to
      decision aids continued to demonstrate reduced rates of: elective invasive
      surgery in favour of conservative options, decision aid versus usual care (RR
      0.8; 95% CI 0.6 to 0.9); and use of menopausal hormones, detailed versus simple
      aid (RR 0.7; 95% CI 0.6 to 1.0). There is now evidence that exposure to decision
      aids results in reduced PSA screening, decision aid versus usual care (RR 0.8;
      95% CI 0.7 to 1.0) . For other decisions, the effect on decisions remains
      variable.As in the previous review, decision aids are no better than comparisons
      in affecting satisfaction with decision making, anxiety, and health outcomes. The
      effects of decision aids on other outcomes (patient-practitioner communication,
      consultation length, continuance, resource use) were inconclusive.There were no
      trials evaluating the IPDAS decision process criteria relating to helping
      patients to recognize a decision needs to be made, understand that values affect
      the decision, or discuss values with the practitioner. AUTHORS' CONCLUSIONS:
      Patient decision aids increase people's involvement and are more likely to lead
      to informed values-based decisions; however, the size of the effect varies across
      studies. Decision aids have a variable effect on decisions. They reduce the use
      of discretionary surgery without apparent adverse effects on health outcomes or
      satisfaction. The degree of detail patient decision aids require for positive
      effects on decision quality should be explored. The effects on continuance with
      chosen option, patient-practitioner communication, consultation length, and cost
      effectiveness need further evaluation.

PMID- 19588322
TI  - Interventions for promoting smoking cessation during pregnancy.
AB  - BACKGROUND: Tobacco smoking in pregnancy remains one of the few preventable
      factors associated with complications in pregnancy, low birthweight, preterm
      birth and has serious long-term health implications for women and babies. Smoking
      in pregnancy is decreasing in high-income countries and increasing in low- to
      middle-income countries and is strongly associated with poverty, low educational
      attainment, poor social support and psychological illness. OBJECTIVES: To assess
      the effects of smoking cessation interventions during pregnancy on smoking
      behaviour and perinatal health outcomes. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (June 2008), the
      Cochrane Tobacco Addiction Group's Trials Register (June 2008), EMBASE, PsycLIT,
      and CINAHL (all from January 2003 to June 2008). We contacted trial authors to
      locate additional unpublished data. SELECTION CRITERIA: Randomised controlled
      trials where smoking cessation during pregnancy was a primary aim of the
      intervention. DATA COLLECTION AND ANALYSIS: Trials were identified and data
      extracted by one person and checked by a second. Subgroup analysis was conducted
      to assess the effect of risk of trial bias, intensity of the intervention and
      main intervention strategy used. MAIN RESULTS: Seventy-two trials are included.
      Fifty-six randomised controlled trials (over 20,000 pregnant women) and nine
      cluster-randomised trials (over 5000 pregnant women) provided data on smoking
      cessation outcomes.There was a significant reduction in smoking in late pregnancy
      following interventions (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.93
      to 0.96), an absolute difference of six in 100 women who stopped smoking during
      pregnancy. However, there is significant heterogeneity in the combined data (I(2)
      > 60%). In the trials with the lowest risk of bias, the interventions had less
      effect (RR 0.97, 95% CI 0.94 to 0.99), and lower heterogeneity (I(2) = 36%).
      Eight trials of smoking relapse prevention (over 1000 women) showed no
      statistically significant reduction in relapse.Smoking cessation interventions
      reduced low birthweight (RR 0.83, 95% CI 0.73 to 0.95) and preterm birth (RR
      0.86, 95% CI 0.74 to 0.98), and there was a 53.91g (95% CI 10.44 g to 95.38 g)
      increase in mean birthweight. There were no statistically significant differences
      in neonatal intensive care unit admissions, very low birthweight, stillbirths,
      perinatal or neonatal mortality but these analyses had very limited power.
      AUTHORS' CONCLUSIONS: Smoking cessation interventions in pregnancy reduce the
      proportion of women who continue to smoke in late pregnancy, and reduce low
      birthweight and preterm birth. Smoking cessation interventions in pregnancy need
      to be implemented in all maternity care settings. Given the difficulty many
      pregnant women addicted to tobacco have quitting during pregnancy, population
      based measures to reduce smoking and social inequalities should be supported.

PMID- 19588323
TI  - The effects of on-screen, point of care computer reminders on processes and
      outcomes of care.
AB  - BACKGROUND: The opportunity to improve care by delivering decision support to
      clinicians at the point of care represents one of the main incentives for
      implementing sophisticated clinical information systems. Previous reviews of
      computer reminder and decision support systems have reported mixed effects,
      possibly because they did not distinguish point of care computer reminders from e
      mail alerts, computer-generated paper reminders, and other modes of delivering
      'computer reminders'. OBJECTIVES: To evaluate the effects on processes and
      outcomes of care attributable to on-screen computer reminders delivered to
      clinicians at the point of care. SEARCH STRATEGY: We searched the Cochrane EPOC
      Group Trials register, MEDLINE, EMBASE and CINAHL and CENTRAL to July 2008, and
      scanned bibliographies from key articles. SELECTION CRITERIA: Studies of a
      reminder delivered via a computer system routinely used by clinicians, with a
      randomised or quasi-randomised design and reporting at least one outcome
      involving a clinical endpoint or adherence to a recommended process of care. DATA
      COLLECTION AND ANALYSIS: Two authors independently screened studies for
      eligibility and abstracted data. For each study, we calculated the median
      improvement in adherence to target processes of care and also identified the
      outcome with the largest such improvement. We then calculated the median absolute
      improvement in process adherence across all studies using both the median outcome
      from each study and the best outcome. MAIN RESULTS: Twenty-eight studies
      (reporting a total of thirty-two comparisons) were included. Computer reminders
      achieved a median improvement in process adherence of 4.2% (interquartile range
      (IQR): 0.8% to 18.8%) across all reported process outcomes, 3.3% (IQR: 0.5% to
      10.6%) for medication ordering, 3.8% (IQR: 0.5% to 6.6%) for vaccinations, and
      3.8% (IQR: 0.4% to 16.3%) for test ordering. In a sensitivity analysis using the
      best outcome from each study, the median improvement was 5.6% (IQR: 2.0% to
      19.2%) across all process measures and 6.2% (IQR: 3.0% to 28.0%) across measures
      of medication ordering. In the eight comparisons that reported dichotomous
      clinical endpoints, intervention patients experienced a median absolute
      improvement of 2.5% (IQR: 1.3% to 4.2%). Blood pressure was the most commonly
      reported clinical endpoint, with intervention patients experiencing a median
      reduction in their systolic blood pressure of 1.0 mmHg (IQR: 2.3 mmHg reduction
      to 2.0 mmHg increase). AUTHORS' CONCLUSIONS: Point of care computer reminders
      generally achieve small to modest improvements in provider behaviour. A minority
      of interventions showed larger effects, but no specific reminder or contextual
      features were significantly associated with effect magnitude. Further research
      must identify design features and contextual factors consistently associated with
      larger improvements in provider behaviour if computer reminders are to succeed on
      more than a trial and error basis.

PMID- 19588327
TI  - First-line drugs for hypertension.
AB  - BACKGROUND: Sustained elevated blood pressure, unresponsive to lifestyle
      measures, leads to a critically important clinical question: What class of drug
      to use first-line? This review answers that question. OBJECTIVES:  PRIMARY
      OBJECTIVE: To quantify the benefits and harms of the major first-line anti
      hypertensive drug classes: thiazides, beta-blockers, calcium channel blockers,
      angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin
      II receptor blockers (ARB). SEARCH STRATEGY: Electronic search of MEDLINE (Jan.
      1966-June 2008), EMBASE, CINAHL, the Cochrane clinical trial register, using
      standard search strategy of the hypertension review group with additional terms.
      SELECTION CRITERIA: Randomized trials of at least one year duration comparing one
      of 6 major drug classes with a placebo or no treatment. More than 70% of people
      must have BP >140/90 mmHg at baseline. DATA COLLECTION AND ANALYSIS: The outcomes
      assessed were mortality, stroke, coronary heart disease (CHD), cardiovascular
      events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals
      due to adverse drug effects. Risk ratio (RR) and a fixed effects model were used
      to combine outcomes across trials. MAIN RESULTS: Of 57 trials identified, 24
      trials with 28 arms, including 58,040 patients met the inclusion criteria.
      Thiazides (19 RCTs) reduced mortality (RR 0.89, 95% CI 0.83, 0.96), stroke (RR
      0.63, 95% CI 0.57, 0.71), CHD (RR 0.84, 95% CI 0.75, 0.95) and CVS (RR 0.70, 95%
      CI 0.66, 0.76). Low-dose thiazides (8 RCTs) reduced CHD (RR 0.72, 95% CI 0.61,
      0.84), but high-dose thiazides (11 RCTs) did not (RR 1.01, 95% CI 0.85, 1.20).
      Beta-blockers (5 RCTs) reduced stroke (RR 0.83, 95% CI 0.72, 0.97) and CVS (RR
      0.89, 95% CI 0.81, 0.98) but not CHD (RR 0.90, 95% CI 0.78, 1.03) or mortality
      (RR 0.96, 95% CI 0.86, 1.07). ACE inhibitors (3 RCTs) reduced mortality (RR 0.83,
      95% CI 0.72-0.95), stroke (RR 0.65, 95% CI 0.52-0.82), CHD (RR 0.81, 95% CI 0.70
      0.94) and CVS (RR 0.76, 95% CI 0.67-0.85). Calcium-channel blocker (1 RCT)
      reduced stroke (RR 0.58, 95% CI 0.41, 0.84) and CVS (RR 0.71, 95% CI 0.57, 0.87)
      but not CHD (RR 0.77 95% CI 0.55, 1.09) or mortality (RR 0.86 95% CI 0.68, 1.09).
      No RCTs were found for ARBs or alpha-blockers. AUTHORS' CONCLUSIONS: First-line
      low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE
      inhibitors and calcium channel blockers may be similarly effective but the
      evidence is less robust. First-line high-dose thiazides and first-line beta
      blockers are inferior to first-line low-dose thiazides.

PMID- 19588328
TI  - Low protein diets for chronic kidney disease in non diabetic adults.
AB  - BACKGROUND: For more than fifty years, low protein diets have been proposed to
      patients with kidney failure. However, the effects of these diets in preventing
      severe kidney failure and the need for maintenance dialysis have not been
      resolved. OBJECTIVES: To determine the efficacy of low protein diets in delaying
      the need to start maintenance dialysis. SEARCH STRATEGY: Cochrane Renal Group
      studies register, the Cochrane Central Register of Controlled studies, MEDLINE,
      and EMBASE. Congress abstracts (American Society of Nephrology since 1990,
      European Dialysis Transplant Association since 1985, International Society of
      Nephrology since 1987). Direct contacts with investigators. SELECTION CRITERIA:
      Randomised studies comparing two different levels of protein intake in adult
      patients suffering from moderate to severe kidney failure, followed for at least
      one year. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      studies and extracted data. Statistical analyses were performed using the random
      effects model and the results expressed as risk ratio (RR) for dichotomous
      outcomes with 95% confidence intervals (CI). Collection of the number of "renal
      deaths" defined as the need for starting dialysis, the death of a patient or a
      kidney transplant during the study. MAIN RESULTS: Ten studies were identified
      from over 40 studies. A total of 2000 patients were analysed, 1002 had received
      reduced protein intake and 998 a higher protein intake. There were 281 renal
      deaths recorded, 113 in the low protein diet and 168 in the higher protein diet
      group (RR 0.68, 95% CI 0.55 to 0.84, P = 0.0002). To avoid one renal death, 2 to
      56 patients need to be treated with a low protein diet during one year. AUTHORS'
      CONCLUSIONS: Reducing protein intake in patients with chronic kidney disease
      reduces the occurrence of renal death by 32% as compared with higher or
      unrestricted protein intake. The optimal level of protein intake cannot be
      confirmed from these studies.

PMID- 19588326
TI  - Single dose oral ibuprofen for acute postoperative pain in adults.
AB  - BACKGROUND: This review updates a 1999 Cochrane review showing that ibuprofen at
      various doses was effective in postoperative pain in single dose studies designed
      to demonstrate analgesic efficacy. New studies have since been published.
      Ibuprofen is one of the most widely used non-steroidal anti-inflammatory (NSAID)
      analgesics both by prescription and as an over-the-counter medicine. Ibuprofen is
      used for acute and chronic painful conditions. OBJECTIVES: To assess analgesic
      efficacy of ibuprofen in single oral doses for moderate and severe postoperative
      pain in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE
      and the Oxford Pain Relief Database for studies to May 2009. SELECTION CRITERIA:
      Randomised, double blind, placebo-controlled trials of single dose orally
      administered ibuprofen (any formulation) in adults with moderate to severe acute
      postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Pain relief or pain
      intensity data were extracted and converted into the dichotomous outcome of
      number of participants with at least 50% pain relief over 4 to 6 hours, from
      which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated.
      Numbers of participants using rescue medication over specified time periods, and
      time to use of rescue medication, were sought as additional measures of efficacy.
      Information on adverse events and withdrawals were collected. MAIN RESULTS:
      Seventy-two studies compared ibuprofen and placebo (9186 participants). Studies
      were predominantly of high reporting quality, and the bulk of the information
      concerned ibuprofen 200 mg and 400 mg. For at least 50% pain relief compared with
      placebo the NNT for ibuprofen 200 mg (2690 participants) was 2.7 (2.5 to 3.0) and
      for ibuprofen 400 mg (6475 participants) it was 2.5 (2.4 to 2.6). The proportion
      with at least 50% pain relief was 46% with 200 mg and 54% with 400 mg.
      Remedication within 6 hours was less frequent with higher doses, with 48%
      remedicating with 200 mg and 42% with 400 mg. The median time to remedication was
      4.7 hours with 200 mg and 5.4 hours with 400 mg. Sensitivity analysis indicated
      that pain model and ibuprofen formulation may both affect the result, with dental
      impaction models and soluble ibuprofen salts producing better efficacy estimates.
      Adverse events were uncommon, and not different from placebo. AUTHORS'
      CONCLUSIONS: The very substantial amount of high quality evidence demonstrates
      that ibuprofen is an effective analgesic in treating postoperative pain. NNTs for
      200 mg and 400 mg ibuprofen did not change significantly from the previous review
      even when a substantial amount of new information was added. New information is
      provided on remedication.

PMID- 19588329
TI  - WITHDRAWN: Homoeopathic Oscillococcinum for preventing and treating influenza and
      influenza-like syndromes.
AB  - BACKGROUND: Influenza is a highly infectious viral disease that is particularly
      common in the winter months. Oscillococcinum is a patented, commercially
      available homoeopathic medicine. The rationale for its use in influenza comes
      from the homoeopathic principle of 'let like be cured by like'. This medicine is
      manufactured from wild duck heart and liver, which are said to be reservoirs for
      influenza viruses. OBJECTIVES: To determine whether homoeopathic Oscillococcinum
      or similar medicines are more effective than placebo in the prevention and
      treatment of influenza and influenza-like syndromes. SEARCH STRATEGY: We updated
      the electronic searches on the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 1, 2006); MEDLINE (January 1966 to February
      2006) and EMBASE (1980 to February 2006). The manufacturers of Oscillococcinum
      were contacted for information. SELECTION CRITERIA: Placebo-controlled trials of
      Oscillococcinum or homeopathically-prepared influenza virus, influenza vaccine or
      avian liver in the prevention and treatment of influenza and influenza-like
      syndromes. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed
      methodological quality independently. MAIN RESULTS: Seven studies were included
      in the review, three prevention trials (number of participants (n) = 2265) and
      four treatment trials (n = 1194). Only two studies reported sufficient
      information to complete data extraction fully. There was no evidence that
      homoeopathic treatment can prevent influenza-like syndrome (relative risk (RR)
      0.64, 95% confidence interval (CI) 0.28 to 1.43). Oscillococcinum treatment
      reduced the length of influenza illness by 0.28 days (95% CI 0.50 to 0.06).
      Oscillococcinum also increased the chances that a patient considered treatment to
      be effective (RR 1.08; 95% CI 1.17 to 1.00). AUTHORS' CONCLUSIONS: Though
      promising, the data were not strong enough to make a general recommendation to
      use Oscillococcinum for first-line treatment of influenza and influenza-like
      syndromes. Further research is warranted but the required sample sizes are large.
      Current evidence does not support a preventative effect of Oscillococcinum-like
      homeopathic medicines in influenza and influenza-like syndromes.

PMID- 19588330
TI  - Buprenorphine for the management of opioid withdrawal.
AB  - BACKGROUND: Managed withdrawal is a necessary step prior to drug-free treatment
      or as the end point of substitution treatment. OBJECTIVES: To assess the
      effectiveness of interventions involving the use of buprenorphine to manage
      opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal
      and adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register
      of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966
      to July 2008), EMBASE (January 1985 to 2008 Week 31), PsycINFO (1967 to 7 August
      2008) and reference lists of articles. SELECTION CRITERIA: Randomised controlled
      trials of interventions involving the use of buprenorphine to modify the signs
      and symptoms of withdrawal in participants who were primarily opioid dependent.
      Comparison interventions involved reducing doses of methadone, alpha(2)
      adrenergic agonists, symptomatic medications or placebo, or different
      buprenorphine-based regimes. DATA COLLECTION AND ANALYSIS: One author assessed
      studies for inclusion and methodological quality, and undertook data extraction.
      Inclusion decisions and the overall process was confirmed by consultation between
      all authors. MAIN RESULTS: Twenty-two studies involving 1736 participants were
      included. The major comparisons were with methadone (5 studies) and clonidine or
      lofexidine (12 studies). Five studies compared different rates of buprenorphine
      dose reduction.Severity of withdrawal is similar for withdrawal managed with
      buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may
      resolve more quickly with buprenorphine. It appears that completion of withdrawal
      treatment may be more likely with buprenorphine relative to methadone (RR 1.18;
      95% CI 0.93 to 1.49, P = 0.18) but more studies are required to confirm
      this.Relative to clonidine or lofexidine, buprenorphine is more effective in
      ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay
      in treatment for longer (SMD 0.92, 95% CI 0.57 to 1.27, P < 0.001), and are more
      likely to complete withdrawal treatment (RR 1.64; 95% CI 1.31 to 2.06, P <
      0.001). At the same time there is no significant difference in the incidence of
      adverse effects, but drop-out due to adverse effects may be more likely with
      clonidine. AUTHORS' CONCLUSIONS: Buprenorphine is more effective than clonidine
      or lofexidine for the management of opioid withdrawal. Buprenorphine may offer
      some advantages over methadone, at least in inpatient settings, in terms of
      quicker resolution of withdrawal symptoms and possibly slightly higher rates of
      completion of withdrawal.

PMID- 19588331
TI  - WITHDRAWN: Corticosteroids for HELLP syndrome in pregnancy.
AB  - BACKGROUND: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome
      is a severe form of pre-eclampsia. Pre-eclampsia is a multi-system disease of
      pregnancy associated with an increase in blood pressure and increased perinatal
      and maternal morbidity and mortality. Eighty per cent of women with HELLP
      syndrome present before term. There are suggestions from observational studies
      that steroid treatment in HELLP syndrome may improve disordered maternal
      hematological and biochemical features and perhaps perinatal mortality and
      morbidity. OBJECTIVES: To summarise the evidence on the effects of
      corticosteroids on maternal and neonatal mortality and morbidity in women with
      HELLP syndrome. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (October 2003). We scanned lists of references
      from review articles and primary studies. SELECTION CRITERIA: Randomised and
      quasi-randomised trials evaluating the effects of adjunctive corticosteroids in
      patients diagnosed with HELLP syndrome were sought. DATA COLLECTION AND ANALYSIS:
      The two authors independently applied inclusion criteria, assessed trial quality
      and extracted relevant data. MAIN RESULTS: Of the five studies reviewed (n =
      170), three were conducted antepartum and two postpartum. Four of the studies
      randomised participants to standard therapy or dexamethasone. One study compared
      dexamethasone with betamethasone. Dexamethasone versus control There were no
      significant differences in the primary outcomes of maternal mortality and
      morbidity due to placental abruption, pulmonary oedema and liver hematoma or
      rupture. Of the secondary maternal outcomes, there was a tendency to a greater
      platelet count increase over 48 hours, statistically significantly less mean
      number of hospital stay days (weighted mean difference (WMD) -4.50, 95%
      confidence interval (CI) -7.13 to -1.87), mean interval (hours) to delivery (41
      +/- 15) versus (15 +/- 4.5) (p = 0.0068) in favour of women allocated to
      dexamethasone.There were no significant differences in perinatal mortality or
      morbidity due to respiratory distress syndrome, need for ventilatory support,
      intracerebral hemorrhage, necrotizing enterocolitis and a five minute Apgar less
      than seven. The mean birthweight was significantly greater in the group allocated
      to dexamethasone (WMD 247.00, 95% CI 65.41 to 428.59).Dexamethasone versus
      betamethasone There were no significant differences in all the maternal and
      perinatal mortality and in primary morbidity outcomes.Women randomised to
      dexamethasone fared significantly better for: oliguria, mean arterial pressure,
      mean increase in platelet count, mean increase in urinary output and liver enzyme
      elevations. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine
      whether adjunctive steroid use in HELLP syndrome decreases maternal and perinatal
      mortality, major maternal and perinatal morbidity.

PMID- 19588332
TI  - Interventions in the management of serum lipids for preventing stroke recurrence.
AB  - BACKGROUND: Studies have shown that interventions which reduce total and low
      density lipoprotein cholesterol levels also reduce coronary heart disease (CHD)
      and stroke events in those with a history of CHD. However, it is uncertain
      whether treatment to alter cholesterol levels can prevent recurrence of either
      stroke or subsequent cardiovascular events and whether differences in outcomes
      exist between classes of lipid-lowering therapy. This is an update of a Cochrane
      review first published in 2002. OBJECTIVES: To investigate the effect of altering
      serum lipids pharmacologically for preventing subsequent cardiovascular disease
      and stroke recurrence in patients with a history of stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched December 2008),
      the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3,
      2008), MEDLINE (1966 to December 2008) and EMBASE (1980 to December 2008). We
      contacted pharmaceutical companies known to produce a lipid-lowering agent for
      information on relevant publications or unpublished work. SELECTION CRITERIA:
      Unconfounded randomised trials of participants aged 18 years and over with a
      history of stroke or transient ischaemic attack (TIA). DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials, assessed quality and
      extracted data. MAIN RESULTS: We included eight studies involving approximately
      10,000 participants. The active interventions were pravastatin, atorvastatin,
      simvastatin, clofibrate, and conjugated oestrogen. Fixed-effect analysis showed
      no overall effect on stroke recurrence but statin therapy alone had a marginal
      benefit in reducing subsequent cerebrovascular events in those with a previous
      history of stroke or TIA (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.77
      to 1.00). There was no evidence that such intervention reduced all-cause
      mortality or sudden death (OR 1.00, 95% CI 0.83 to 1.20). Three statin trials
      showed a reduction in subsequent serious vascular events (OR 0.74, 95% CI 0.67 to
      0.82). AUTHORS' CONCLUSIONS: There is evidence that statin therapy in patients
      with a history of ischaemic stroke or TIA significantly reduces subsequent major
      coronary events but only marginally reduces the risk of stroke recurrence. There
      is no clear evidence of beneficial effect from statins in those with previous
      haemorrhagic stroke and it is unclear whether statins should be started
      immediately post stroke or later. In view of this and the evidence of the benefit
      of statin therapy in those with a history of CHD, patients with ischaemic stroke
      or TIA, with or without a history of established CHD, should receive statins.

PMID- 19588333
TI  - Methadone maintenance therapy versus no opioid replacement therapy for opioid
      dependence.
AB  - BACKGROUND: Methadone maintenance was the first widely used opioid replacement
      therapy to treat heroin dependence, and it remains the best-researched treatment
      for this problem. Despite the widespread use of methadone in maintenance
      treatment for opioid dependence in many countries, it is a controversial
      treatment whose effectiveness has been disputed. OBJECTIVES: To evaluate the
      effects of methadone maintenance treatment (MMT) compared with treatments that
      did not involve opioid replacement therapy (i.e., detoxification, offer of drug
      free rehabilitation, placebo medication, wait-list controls) for opioid
      dependence. SEARCH STRATEGY: We searched the following databases up to Dec 2008:
      the Cochrane Controlled Trials Register, EMBASE, PubMED, CINAHL, Current
      Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council
      of Australia (ADCA) [www.adca.org.au], Australian Drug Foundation (ADF-VIC)
      [www.adf.org.au], Centre for Education and Information on Drugs and Alcohol
      (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library
      of Congress databases, available NIDA monographs and the College on Problems of
      Drug Dependence Inc. proceedings, the reference lists of all identified studies
      and published reviews; authors of identified RCTs were asked about other
      published or unpublished relevant RCTs. SELECTION CRITERIA: All randomised
      controlled clinical trials of methadone maintenance therapy compared with either
      placebo maintenance or other non-pharmacological therapy for the treatment of
      opioid dependence. DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers
      separately and independently, rating methodological quality of sequence
      generation, concealment of allocation and bias. Data were extracted independently
      for meta-analysis and double-entered. MAIN RESULTS: Eleven studies met the
      criteria for inclusion in this review, all were randomised clinical trials, two
      were double-blind. There were a total number of 1969 participants. The sequence
      generation was inadequate in one study, adequate in five studies and unclear in
      the remaining studies. The allocation of concealment was adequate in three
      studies and unclear in the remaining studies. Methadone appeared statistically
      significantly more effective than non-pharmacological approaches in retaining
      patients in treatment and in the suppression of heroin use as measured by self
      report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but not
      statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25)
      or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39). AUTHORS' CONCLUSIONS: Methadone
      is an effective maintenance therapy intervention for the treatment of heroin
      dependence as it retains patients in treatment and decreases heroin use better
      than treatments that do not utilise opioid replacement therapy. It does not show
      a statistically significant superior effect on criminal activity or mortality.

PMID- 19588335
TI  - Single dose oral oxycodone and oxycodone plus paracetamol (acetaminophen) for
      acute postoperative pain in adults.
AB  - BACKGROUND: Oxycodone is a strong opioid agonist used to treat severe pain. It is
      commonly combined with milder analgesics such as paracetamol. This review updates
      a previous review that concluded, based on limited data, that all doses of
      oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in
      postoperative pain, but with increased incidence of adverse events compared with
      placebo. Additional new studies provide more reliable estimates of efficacy and
      harm. OBJECTIVES: To assess efficacy, duration of action, and associated adverse
      events of single dose oral oxycodone, with or without paracetamol, in acute
      postoperative pain in adults. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE
      and Oxford Pain Relief Database, searched in May 2009. SELECTION CRITERIA:
      Randomised, double blind, placebo-controlled trials of single dose orally
      administered oxycodone, with or without paracetamol, in adults with moderate to
      severe acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Pain relief or pain
      intensity data were extracted and converted into the dichotomous outcome of
      number of participants with at least 50% pain relief over 4 to 6 hours, from
      which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated.
      Numbers of participants remedicating over specified time periods, and time-to-use
      of rescue medication, were sought as additional measures of efficacy. Adverse
      events and withdrawals information was collected. MAIN RESULTS: This updated
      review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone
      compared with placebo, the NNT for at least 50% pain relief was 4.6 (95%
      Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the
      NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with
      combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus
      paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed
      rescue medication over 6 hours at the higher dose. Adverse events occurred more
      frequently with combination therapy than placebo, but were generally described as
      mild to moderate in severity and rarely led to withdrawal. AUTHORS' CONCLUSIONS:
      Single dose oxycodone is an effective analgesic in acute postoperative pain at
      doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy
      increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg
      provides good analgesia to half of those treated, comparable to commonly used non
      steroidal anti-inflammatory drugs, with the benefit of longer duration of action.

PMID- 19588337
TI  - High frequency oscillatory ventilation versus conventional ventilation for
      infants with severe pulmonary dysfunction born at or near term.
AB  - BACKGROUND: Pulmonary disease is a major cause of mortality and morbidity in term
      and near term infants. Conventional ventilation (CV) has been used for many years
      but may lead to lung injury, require the subsequent use of more invasive
      treatment such as extracorporeal membrane oxygenation (ECMO), or result in death.
      There are some observational studies indicating that high frequency oscillatory
      ventilation (HFOV) may be more effective in these infants as compared to CV.
      OBJECTIVES: To determine the effect of HFOV as compared with CV on mortality and
      morbidity in infants born at 35 weeks gestational age or more with severe
      respiratory failure requiring mechanical ventilation. SEARCH STRATEGY: Standard
      search methods of the Cochrane Neonatal Review group were used. These included
      searches in January 2009 of The Cochrane Library, MEDLINE, EMBASE, previous
      reviews including cross references, abstracts, conferences and symposia
      proceedings, expert informants, and journal hand searching by the Cochrane
      Collaboration. SELECTION CRITERIA: Randomized or quasi-randomized trials
      comparing HFOV and CV in term or near term infants with intractable respiratory
      failure were included in this review. DATA COLLECTION AND ANALYSIS: The standard
      methods of the Cochrane Neonatal Review Group were used. The investigators
      separately extracted, assessed and coded all data for each study. Any
      disagreement was resolved by discussion. Data were synthesized using risk ratio
      [RR with (95% confidence intervals, CI)] and mean difference (with standard
      deviation, SD). MAIN RESULTS: Two trials met the inclusion criteria. One trial
      involving the "elective" use of HFOV randomized 118 infants at the start of CV.
      The other trial of "rescue" HFOV randomized 81 infants with later respiratory
      failure on CV. Neither trial showed evidence of a reduction in mortality at 28
      days or in failed therapy on the assigned mode of ventilation requiring cross
      over to the other mode. Neither study reported significant differences in the
      risk of pulmonary air leak, chronic lung disease (28 days or more in oxygen) or
      intracranial injury. In the study of elective HFOV, there was no difference noted
      in days on a ventilator or days in hospital. In the one rescue study, there was
      no difference in the risk of needing extracorporeal membrane oxygenation.
      AUTHORS' CONCLUSIONS: There are no data from randomized controlled trials
      supporting the use of rescue HFOV in term or near term infants with severe
      pulmonary dysfunction. The area is complicated by diverse pathology in such
      infants and by the occurrence of other interventions (surfactant, inhaled nitric
      oxide, inotropes). Randomized controlled trials are needed to establish the role
      of elective or rescue HFOV in near term and term infants with pulmonary
      dysfunction before widespread use of this mode of ventilation in such infants.

PMID- 19588336
TI  - Mifepristone for induction of labour.
AB  - BACKGROUND: The steroid hormone, progesterone, inhibits contractions of the
      pregnant uterus at all gestations. Antiprogestins (including mifepristone) have
      been developed to antagonise the action of progesterone, and have a recognised
      role in medical termination of early or mid-trimester pregnancy. Animal studies
      have suggested that mifepristone may also have a role in inducing labour in late
      pregnancy. OBJECTIVES: To determine the effects of mifepristone for third
      trimester cervical ripening or induction of labour. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register and reference lists
      of relevant papers (May 2009). SELECTION CRITERIA: Clinical trials comparing
      mifepristone used for third trimester cervical ripening or labour induction with
      placebo/no treatment or other labour induction methods. DATA COLLECTION AND
      ANALYSIS: A strategy was developed to deal with the large volume and complexity
      of trial data relating to labour induction. This involved a two-stage method of
      data extraction. For this update, two review authors independently assessed trial
      quality and extracted data. MAIN RESULTS: Ten trials (1108 women) are included.
      Compared to placebo, mifepristone treated women were more likely to be in labour
      or to have a favourable cervix at 48 hours (risk ratio (RR) 2.41, 95% confidence
      intervals (CI) 1.70 to 3.42) and this effect persisted at 96 hours (RR 3.40, 95%
      CI 1.96 to 5.92). They were less likely to need augmentation with oxytocin (RR
      0.80, 95% CI 0.66 to 0.97). Mifepristone treated women were less likely to
      undergo caesarean section (RR 0.74, 95% CI 0.60 to 0.92) but more likely to have
      an instrumental delivery (RR 1.43, 95% CI 1.04 to 1.96). Women receiving
      mifepristone were less likely to undergo a caesarean section as a result of
      failure to induce labour (RR 0.40, 95% CI 0.20 to 0.80). There is insufficient
      evidence to support a particular dose but a single dose of 200 mg mifepristone
      appears to be the lowest effective dose for cervical ripening (increased
      likelihood of cervical ripening at 72 hours (RR 2.13, 95% CI 1.15 to 3.97).
      Abnormal fetal heart rate patterns were more common after mifepristone treatment
      (RR 1.85, 95% CI 1.17 to 2.93), but there was no evidence of differences in other
      neonatal outcomes. There is insufficient information on the occurrence of uterine
      rupture/dehiscence in the reviewed studies. AUTHORS' CONCLUSIONS: There is
      insufficient information available from clinical trials to support the use of
      mifepristone to induce labour. However, the studies suggest that mifepristone is
      better than placebo in reducing the likelihood of caesarean sections being
      performed for failed induction of labour; therefore, this may justify future
      trials comparing mifepristone with the routine cervical ripening agents currently
      in use. There is little information on effects on the baby.

PMID- 19588338
TI  - WITHDRAWN: Insulin-sensitising drugs for polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by anovulation,
      hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with
      an increase in cardiovascular risk and the development of diabetes mellitus. If
      insulin sensitising agents such as metformin are effective in treating features
      of PCOS, then they could have wider health benefits than just treating the
      symptoms of the syndrome. OBJECTIVES: To assess the effectiveness of insulin
      sensitising drugs in improving clinical and biochemical features of PCOS. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group
      trials register (searched September 2008 ), the Cochrane Central Register of
      Controlled Trials (Cochrane Library, September 2008), MEDLINE (January 1966 to
      September 2008), and EMBASE (January 1985 to September 2008). SELECTION CRITERIA:
      Randomised controlled trials which investigated the effect of insulin sensitising
      drugs compared with either placebo or no treatment, or compared with an ovulation
      induction agent. DATA COLLECTION AND ANALYSIS: Thirty nine trials (3576 subjects)
      were included for analysis, 31 of them using metformin and involving 2625
      participants. MAIN RESULTS: Meta-analysis showed that metformin is effective in
      achieving ovulation in women with PCOS with odds ratios of 2.21(CI 1.57 to 3.10)
      for metformin versus placebo and 3.93(CI 2.32 to 6.65) for metformin and
      clomiphene versus clomiphene alone. An analysis of pregnancy rates suggests a
      significant treatment effect for metformin and clomiphene (OR 1.58, CI 1.20 to
      2.07). Nevertheless, these benefits were not translated into live birth
      rates.Metformin has a significant effect in reducing fasting insulin levels (WMD 
      4.20 mIU/L, CI -7.68 to -0.73); however, the reduction was only significant in
      the non-obese group (BMI < 30 kg/m2). Treatment effect on serum testosterone
      concentration was observed; but the magnitude of the reduction was greater in the
      non-obese group compared with the obese group (WMD -1.79 versus. -0.30 nmol/L).
      Metformin has no effect on serum lipid profiles. Metformin was also associated
      with a significantly higher incidence of gastrointestinal disturbance, but no
      serious adverse effects were reported. AUTHORS' CONCLUSIONS: In agreement with
      the previous review, metformin is still of benefit in improving ovulation and
      pregnancy rates. However, metformin does not improve live birth whether it is
      used alone or in combination with clomiphene. In addition, metformin has limited
      effect on metabolic parameters, especially in obese women with PCOS. Therefore,
      the use of metformin in improvement of reproductive outcomes or in reducing the
      risk of developing metabolic syndrome in women with PCOS appears to be limited.

PMID- 19588339
TI  - WITHDRAWN: Surgical interventions for treating distal radial fractures in adults.
AB  - BACKGROUND: Fracture of the distal radius is a common clinical problem,
      particularly in older white women with osteoporosis. OBJECTIVES: To determine
      when, and if so what type of, surgical intervention is the most appropriate
      treatment for fractures of the distal radius in adults. SEARCH STRATEGY: We
      searched the Cochrane Bone, Joint and Muscle Trauma Group specialised register
      (November 2002), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to 2003
      Week 8), CINAHL (1982 to February 2003), the National Research Register (Issue 1,
      2003), PEDro, conference proceedings and reference lists of articles. No language
      restrictions were applied. SELECTION CRITERIA: Randomised or quasi-randomised
      clinical trials involving skeletally mature patients with a fracture of the
      distal radius, which compared surgical treatment with conservative treatment,
      different types of surgical intervention or the duration of immobilisation after
      surgery. The main categories of surgical intervention were external fixation,
      percutaneous pinning, open reduction and internal fixation, and the insertion of
      bone scaffolding materials. DATA COLLECTION AND ANALYSIS: All trials, meeting the
      selection criteria, were independently assessed by both reviewers for
      methodological quality. Data were extracted for anatomical, functional and
      clinical outcomes (including complications). The trials were grouped into
      categories relating to the main comparisons and types of surgical intervention.
      Despite clear heterogeneity in the characteristics of comparable trials, pooling
      of data was undertaken where possible and appropriate. MAIN RESULTS: Forty eight
      trials, examining 25 treatment comparisons, met the inclusion criteria of this
      review. These involved a total of 3371 mainly female and older patients with
      generally displaced, often comminuted and potentially or evidently unstable
      fractures. Nearly half of the trials compared surgery with plaster cast
      immobilisation. Summarising the outcomes was hampered by the variation between
      the studies in participant characteristics, interventions, quality of trial
      methodology and reporting, and outcome measurement. Surgical methods were usually
      associated with better anatomical appearance after fracture healing, but there
      was inadequate evidence to confirm that these had resulted in better functional
      and clinical outcomes for the patients. AUTHORS' CONCLUSIONS: The 48 randomised
      trials do not provide robust evidence for most of the decisions necessary in the
      management of these fractures. Although, in particular, there is some evidence to
      support the use of external fixation or percutaneous pinning, their precise role
      and methods are not established. It is also unclear whether surgical intervention
      of most fracture types will produce consistently better long-term outcomes.There
      is a need for good quality evidence for the surgical management of these
      fractures.

PMID- 19588340
TI  - Treatment of Lennox-Gastaut syndrome.
AB  - BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder,
      characterised by epileptic seizures, a characteristic electroencephalogram (EEG),
      psychomotor delay and behaviour disorders. It occurs more frequently in males and
      onset is usually before the age of eight, with a peak between three and five
      years. Late cases occurring in adolescence and early adulthood have rarely been
      reported. Language is frequently affected, with both slowness in ideation and
      expression in addition to difficulties of motor dysfunction. Severe behavioural
      disorders (for example hyperactivity, aggressiveness and autistic tendencies) and
      personality disorders are nearly always present. There is also a tendency for
      psychosis to develop with time. The long-term prognosis is poor; although the
      epilepsy often improves, complete seizure freedom is rare and conversely the
      mental and psychiatric disorders tend to worsen with time. OBJECTIVES: To compare
      the effects of pharmaceutical therapies used to treat Lennox-Gastaut syndrome in
      terms of control of seizures and adverse effects. Many people who suffer from
      this syndrome will already be receiving other antiepileptic medications at the
      time of their entry into a trial. However, for the purpose of this review we will
      only consider the effect of the single therapeutic agent being trialed (often as
      add-on therapy). SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's
      Specialized Register (February 2009), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), and MEDLINE (1950 to
      January 2009). We also searched EMBASE (1980 to March 2003). We imposed no
      language restrictions. We searched the ISRCTN register for ongoing trials and in
      addition, we contacted pharmaceutical companies and colleagues in the field to
      seek any unpublished or ongoing studies. SELECTION CRITERIA: All randomised
      controlled trials (RCTs) of the administration of drug therapy to patients with
      Lennox-Gastaut syndrome. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data. Analysis included assessing study quality, as well
      as statistical analysis of the effects on overall seizure rates and effects on
      specific seizure types (e.g. drop attacks), adverse effects and mortality. MAIN
      RESULTS: We found seven RCTs, but were unable to perform any meta-analysis,
      because each trial looked at different populations, different therapies and
      considered different outcomes. AUTHORS' CONCLUSIONS: The optimum treatment for
      Lennox-Gastaut syndrome remains uncertain and no study to date has shown any one
      drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate
      may be helpful as add-on therapy. Until further research has been undertaken,
      clinicians will need to continue to consider each patient individually, taking
      into account the potential benefit of each therapy weighed against the risk of
      adverse effects.

PMID- 19588341
TI  - Treatments for gestational diabetes.
AB  - BACKGROUND: Gestational diabetes (GDM) affects 3% to 6% of all pregnancies. Women
      are often intensively managed with increased obstetric monitoring, dietary
      regulation, and insulin. However, there has been no sound evidence base to
      support intensive treatment. The key issue for clinicians and consumers is
      whether treatment of GDM improves perinatal outcome. OBJECTIVES: To compare the
      effect of alternative treatment policies for GDM on both maternal and infant
      outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (January 2009) and bibliographies of relevant papers.
      SELECTION CRITERIA: Randomised controlled trials comparing alternative management
      strategies for women with GDM and impaired glucose tolerance in pregnancy. DATA
      COLLECTION AND ANALYSIS: Two authors and a member of the Cochrane Pregnancy and
      Childbirth Group's editorial team extracted and checked data independently.
      Disagreements were resolved through discussion with the third author. MAIN
      RESULTS: Eight randomised controlled trials (1418 women) were included.Caesarean
      section rate was not significantly different when comparing any specific
      treatment with routine antenatal care (ANC) including data from five trials with
      1255 participants (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.80 to
      1.12). However, when comparing oral hypoglycaemics with insulin as treatment for
      GDM, there was a significant reduction (RR 0.46, 95% CI 0.27 to 0.77, two trials,
      90 participants). There was a reduction in the risk of pre-eclampsia with
      intensive treatment (including dietary advice and insulin) compared to routine
      ANC (RR 0.65, 95% CI 0.48 to 0.88, one trial, 1000 participants). More women had
      their labours induced when given specific treatment compared to routine ANC (RR
      1.33, 95% CI 1.13 to 1.57, two trials, 1068 participants). The composite outcome
      of perinatal morbidity (death, shoulder dystocia, bone fracture and nerve palsy)
      was significantly reduced for those receiving intensive treatment for mild GDM
      compared to routine ANC (RR 0.32, 95% CI 0.14 to 0.73, one trial, 1030
      infants).There was a reduction in the proportion of infants weighing more than
      4000 grams (RR 0.46, 95% CI 0.34 to 0.63, one trial, 1030 infants) and the
      proportion of infants weighing greater than the 90th birth centile (RR 0.55, 95%
      CI 0.30 to 0.99, three trials, 223 infants) of mothers receiving specific
      treatment for GDM compared to routine ANC. However, there was no statistically
      significant difference in this proportion between infants of mothers receiving
      oral drugs compared to insulin as treatment for GDM. AUTHORS' CONCLUSIONS:
      Specific treatment including dietary advice and insulin for mild GDM reduces the
      risk of maternal and perinatal morbidity. However, it is associated with higher
      risk of labour induction. More research is needed to assess the impact of
      different types of intensive treatment, including oral drugs and insulin, on
      individual short- and long-term infant outcomes.

PMID- 19588334
TI  - Progressive resistance strength training for improving physical function in older
      adults.
AB  - BACKGROUND: Muscle weakness in old age is associated with physical function
      decline. Progressive resistance strength training (PRT) exercises are designed to
      increase strength. OBJECTIVES: To assess the effects of PRT on older people and
      identify adverse events. SEARCH STRATEGY: We searched the Cochrane Bone, Joint
      and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2),
      MEDLINE (1966 to May 01, 2008), EMBASE (1980 to February 06 2007), CINAHL (1982
      to July 01 2007) and two other electronic databases. We also searched reference
      lists of articles, reviewed conference abstracts and contacted authors. SELECTION
      CRITERIA: Randomised controlled trials reporting physical outcomes of PRT for
      older people were included. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected trials, assessed trial quality and extracted data. Data
      were pooled where appropriate. MAIN RESULTS: One hundred and twenty one trials
      with 6700 participants were included. In most trials, PRT was performed two to
      three times per week and at a high intensity. PRT resulted in a small but
      significant improvement in physical ability (33 trials, 2172 participants; SMD
      0.14, 95% CI 0.05 to 0.22). Functional limitation measures also showed
      improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179
      participants, MD 0.08 m/s, 95% CI 0.04 to 0.12); and a moderate to large effect
      for getting out of a chair (11 trials, 384 participants, SMD -0.94, 95% CI -1.49
      to -0.38). PRT had a large positive effect on muscle strength (73 trials, 3059
      participants, SMD 0.84, 95% CI 0.67 to 1.00). Participants with osteoarthritis
      reported a reduction in pain following PRT(6 trials, 503 participants, SMD -0.30,
      95% CI -0.48 to -0.13). There was no evidence from 10 other trials (587
      participants) that PRT had an effect on bodily pain. Adverse events were poorly
      recorded but adverse events related to musculoskeletal complaints, such as joint
      pain and muscle soreness, were reported in many of the studies that prospectively
      defined and monitored these events. Serious adverse events were rare, and no
      serious events were reported to be directly related to the exercise programme.
      AUTHORS' CONCLUSIONS: This review provides evidence that PRT is an effective
      intervention for improving physical functioning in older people, including
      improving strength and the performance of some simple and complex activities.
      However, some caution is needed with transferring these exercises for use with
      clinical populations because adverse events are not adequately reported.

PMID- 19588342
TI  - WITHDRAWN: Ergonomic and physiotherapeutic interventions for treating work
      related complaints of the arm, neck or shoulder in adults.
AB  - BACKGROUND: Conservative interventions such as physiotherapy and ergonomic
      adjustments (such as keyboard adjustments or ergonomic advice) play a major role
      in the treatment of most work-related complaints of the arm, neck or shoulder
      (CANS). OBJECTIVES: This systematic review aims to determine whether conservative
      interventions have a significant impact on outcomes for work-related CANS in
      adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group Specialised Register (March 2005) and Cochrane Rehabilitation and Related
      Therapies Field Specialised Register (March 2005), the Cochrane Controlled Trials
      Register (The Cochrane Library, Issue 1, 2005), PubMed, EMBASE, CINAHL, AMED and
      reference lists of articles. The date of the last search was March 2005. No
      language restrictions were applied. SELECTION CRITERIA: We included randomised
      controlled trials studying conservative interventions (e.g. exercises,
      relaxation, physical applications, biofeedback, myofeedback and work-place
      adjustments) for adults suffering CANS. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected trials from the search yield, assessed the methodological
      quality using the Delphi list, and extracted relevant data. We pooled data or, in
      the event of clinical heterogeneity or lack of data, we used a rating system to
      assess levels of evidence. MAIN RESULTS: For this update we included six
      additional studies; 21 trials in total. Seventeen trials included people with
      chronic non-specific neck or shoulder complaints, or non-specific upper extremity
      disorders. Over 25 interventions were evaluated; five main subgroups of
      interventions could be determined: exercises, manual therapy, massage,
      ergonomics, and energised splint. Overall, the quality of the studies was poor.In
      14 studies a form of exercise was evaluated, and contrary to the previous review
      we now found limited evidence about the effectiveness of exercises when compared
      to massage and conflicting evidence when exercises are compared to no treatment.
      In this update there is limited evidence for adding breaks during computer work;
      massage as add-on treatment on manual therapy, manual therapy as add-on treatment
      on exercises; and some keyboard designs when compared to other keyboards or
      placebo in participants with carpal tunnel syndrome. AUTHORS' CONCLUSIONS: There
      is limited evidence for the effectiveness of keyboards with an alternative force
      displacement of the keys or an alternative geometry, and limited evidence for the
      effectiveness of exercises compared to massage; breaks during computer work
      compared to no breaks; massage as an add-on treatment to manual therapy; and
      manual therapy as an add-on treatment to exercises.

PMID- 19588344
TI  - Surgical approach to hysterectomy for benign gynaecological disease.
AB  - BACKGROUND: The three approaches to hysterectomy for benign disease are abdominal
      hysterectomy (AH), vaginal hysterectomy (VH), and laparoscopic hysterectomy (LH).
      Laparoscopic hysterectomy has three further subdivisions depending on the part of
      the procedure performed laparoscopically. OBJECTIVES: To assess the most
      beneficial and least harmful surgical approach to hysterectomy for women with
      benign gynaecological conditions. SEARCH STRATEGY: We searched the Cochrane
      Menstrual Disorders and Subfertility Group Specialised Register of controlled
      trials (15 August 2008), CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE
      (1950 to August 2008), EMBASE (1980 to August 2008), Biological Abstracts (1969
      to August 2008), the National Research Register, and relevant citation lists.
      SELECTION CRITERIA: Only randomised controlled trials comparing one surgical
      approach to hysterectomy with another were included. DATA COLLECTION AND
      ANALYSIS: Independent selection of trials and data extraction were employed
      following Cochrane guidelines. MAIN RESULTS: There were 34 included studies with
      4495 women. The benefits of VH versus AH were speedier return to normal
      activities (mean difference (MD) 9.5 days), fewer febrile episodes or unspecified
      infections (odds ratio (OR) 0.42), and shorter duration of hospital stay (MD 1.1
      days). The benefits of LH versus AH were speedier return to normal activities (MD
      13.6 days), lower intraoperative blood loss (MD 45 cc), a smaller drop in
      haemoglobin (MD 0.55 g/dl), shorter hospital stay (MD 2.0 days), and fewer wound
      or abdominal wall infections (OR 0.31) at the cost of more urinary tract (bladder
      or ureter) injuries (OR 2.41) and longer operation time (MD 20.3 minutes). The
      benefits of LAVH versus TLH were fewer febrile episodes or unspecified infection
      (OR 3.77) and shorter operation time (MD 25.3 minutes). There was no evidence of
      benefits of LH versus VH and the operation time (MD 39.3 minutes) as well as
      substantial bleeding (OR 2.76) were increased in LH. For some important outcomes,
      the analyses were underpowered to detect important differences or they were
      simply not reported in trials. Data were absent for many important long-term
      outcome measures. AUTHORS' CONCLUSIONS: Because of equal or significantly better
      outcomes on all parameters, VH should be performed in preference to AH where
      possible. Where VH is not possible, LH may avoid the need for AH however the
      length of the surgery increases as the extent of the surgery performed
      laparoscopically increases. The surgical approach to hysterectomy should be
      decided by the woman in discussion with her surgeon in light of the relative
      benefits and hazards.

PMID- 19588343
TI  - Antihypertensive treatment for kidney transplant recipients.
AB  - BACKGROUND: In some nontransplant populations, effects of different
      antihypertensive drug classes vary. Relative effects in kidney transplant
      recipients are uncertain. OBJECTIVES: To assess comparative effects of different
      classes of antihypertensive agents in kidney transplant recipients. SEARCH
      STRATEGY: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials,
      conference proceedings and reference lists of identified studies were searched.
      SELECTION CRITERIA: Randomised controlled trials of any antihypertensive agent
      applied to kidney transplant recipients for at least two weeks were included.
      DATA COLLECTION AND ANALYSIS: Data was extracted by two investigators
      independently. Study quality, transplant outcomes and other patient centred
      outcomes were assessed using random effects meta-analysis. Risk ratios (RR) for
      dichotomous outcomes and mean difference (MD) for continuous outcomes, both with
      95% confidence intervals (CI) were calculated. Stratified analyses and meta
      regression were used to investigate heterogeneity. MAIN RESULTS: We identified 60
      studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants)
      compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445
      participants) compared angiotensin converting enzyme inhibitors (ACEi) to
      placebo/no treatment and seven studies (405 participants) compared CCB to ACEi.
      CCB compared to placebo/no treatment (plus additional agents in either arm as
      required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved
      glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on
      ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95%
      CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In
      direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to
      -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD 
      12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI
      1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to
      140.35). Other drug comparisons were compared in small numbers of participants
      and studies. AUTHORS' CONCLUSIONS: These data suggest that CCB may be preferred
      as first line agents for hypertensive kidney transplant recipients. ACEi have
      some detrimental effects in kidney transplant recipients. More high quality
      studies reporting patient centred outcomes are required.

PMID- 19588345
TI  - WITHDRAWN: Orthotic devices after stroke and other non-progressive brain lesions.
AB  - BACKGROUND: Post-stroke motor impairments cause difficulty controlling the joints
      of the affected limbs to produce useful movements. One way to manage this to use
      an orthosis to control the movement of the affected joints but evidence for their
      benefit is lacking. OBJECTIVES: To determine the effectiveness of upper or lower
      limb orthoses on activity and impairment in people with stroke and other non
      progressive brain lesions. SEARCH STRATEGY: In February 2007 we searched the
      trials registers of the Cochrane Stroke, Movement Disorders and Injuries Groups,
      the Cochrane Database of Systematic Reviews and the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2007), MEDLINE (from 1966),
      EMBASE (from 1980), CINAHL (from 1983), AMED (from 1985), PsycINFO (from 1967)
      and RECAL (from 1990), and other databases and trials registers. We screened
      reference lists, contacted lead authors and other researchers in the field.
      SELECTION CRITERIA: We included randomised controlled trials of orthoses applied
      to the upper or lower limb in people with stroke and other non-progressive brain
      lesions. DATA COLLECTION AND ANALYSIS: Two review authors independently
      identified trials, extracted data, and assessed trial quality. Results for
      continuous outcomes were combined and analysed using mean difference or
      standardised mean difference, both with 95% confidence intervals and fixed-effect
      model. MAIN RESULTS: We analysed 14 trials with 429 participants. The overall
      effect of lower limb orthoses on walking disability (speed), walking impairment
      (step/stride length) and balance impairment (weight distribution in standing) was
      significant and beneficial. There was no significant effect on postural sway
      (balance impairment) or mobility disability but the numbers of studies and
      participants were low. However, these were all cross-over trials that looked at
      the immediate effect while wearing the orthosis; they did not assess the effects
      of wearing an orthosis over the long term. Upper limb orthoses showed no effect
      on upper limb function, range of movement at the wrist, fingers or thumb, nor
      pain. However, this was based on only three trials. AUTHORS' CONCLUSIONS: A lower
      limb orthosis can improve walking and balance but the included studies have only
      examined the immediate effects while wearing the orthosis; the effects of long
      term use have not been investigated. An upper limb orthosis does not effect on
      upper limb function, range of movement at the wrist, fingers or thumb, nor pain,
      but this conclusion is based on only three trials.

PMID- 19588346
TI  - Heparin for the prevention of venous thromboembolism in general medical patients
      (excluding stroke and myocardial infarction).
AB  - BACKGROUND: Venous thromboembolic disease has been extensively studied in
      surgical patients. The benefit of thromboprophylaxis is now generally accepted,
      but it is medical patients who make up the greater proportion of the hospital
      population. Medical patients differ from surgical patients with regard to their
      health and the pathogenesis of thromboembolism and the impact that preventative
      measures can have. The extensive experience from thromboprophylaxis studies in
      surgical patients is therefore not necessarily applicable to non-surgical
      patients. OBJECTIVES: To determine the effectiveness and safety of heparin
      thromboprophylaxis in general medical patients. SEARCH STRATEGY: The Cochrane
      Peripheral Vascular Diseases Group searched their Specialised Register (last
      searched 24 April 2009) and the Cochrane Central Register of Controlled Trials in
      The Cochrane Library (last searched Issue 2, 2009)We handsearched meeting
      abstracts, and consulted with colleagues and investigators as well as the
      manufacturers of the various LMWH preparations to identify unpublished or missed
      studies. SELECTION CRITERIA: Randomised controlled trials comparing
      unfractionated heparin (UFH) or low molecular weight heparin (LMWH) with placebo
      or no treatment, or comparing UFH with LMWH. DATA COLLECTION AND ANALYSIS: One
      author identified possible trials, and the other author confirmed eligibility for
      inclusion in the review. Both authors extracted the data. Disagreements were
      resolved by discussion. We performed the meta-analysis as a fixed-effect model
      with relative risks. MAIN RESULTS: A significant risk reduction in deep vein
      thrombosis (DVT) by 60% (relative risk (RR) 0.40; 95% confidence interval CI 0.31
      to 0.53; P < 0.00001) and pulmonary embolism (PE) by 42% (RR 0.58; 95% CI 0.43 to
      0.80; P = 0.0007) was observed with heparin compared with placebo or no
      treatment. However, heparin resulted in a significant increase in major
      haemorrhage (RR 2.18; 95% CI 1.28 to 3.72; P = 0.004) and minor haemorrhage (RR
      1.74; 95% CI 1.26 to 2.41; P = 0.0008). There was no statistically significant
      difference in efficacy between LMWH and UFH. There was a statistically
      significant 72% risk reduction in major bleeding when LMWH was compared with UFH
      (RR 0.28; 95% CI 0.10 to 0.78; P = 0.02). AUTHORS' CONCLUSIONS: The data from
      this review support the use of heparin thromboprophylaixs in medical patients
      presenting with an acute medical illness. Although the analysis found no
      significant difference in efficacy between LMWH and UFH, it did note differences
      in the incidence of DVT and clinical PE with a significantly reduced risk of
      bleeding in favour of LMWH.

PMID- 19588347
TI  - Rehabilitation interventions for foot drop in neuromuscular disease.
AB  - BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to
      describe weakness or contracture of the muscles around the ankle joint. It may
      arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic
      review of randomised trials for the treatment of foot drop resulting from
      neuromuscular disease. SEARCH STRATEGY: In this update, we searched the Cochrane
      Neuromuscular Disease Group Trials Register (April 2009), MEDLINE (January 1966
      to April 24 2009), EMBASE January 1980 to April 24 2009), CINAHL (January 1982 to
      May 6 2009), AMED (January 1985 to April 24 2009), the British Nursing Index
      (January 1985 to January 2008) and Royal College of Nursing Journal of Databases
      (January 1985 to January 2008). SELECTION CRITERIA: Randomised and quasi
      randomised trials of physical, orthotic and surgical treatments for foot drop
      resulting from lower motor neuron or muscle disease and related contractures were
      included. People with primary joint disease were excluded. Interventions included
      a 'wait and see' approach, physiotherapy, orthoses, surgery and pharmacological
      therapy. The primary outcome measure was quantified ability to walk whilst
      secondary outcome measures included range of movement, dorsiflexor torque and
      strength, measures of activity and participation, quality of life and adverse
      effects. DATA COLLECTION AND ANALYSIS: Methodological quality was evaluated by
      two authors using the van Tulder criteria. Four studies with a total of n = 152
      participants were included in the update to the original review. Heterogeneity of
      the studies precluded pooling the data. MAIN RESULTS: Early surgery did not
      significantly affect walking speed in a trial including 20 children with Duchenne
      muscular dystrophy. Both groups deteriorated during the 12 months follow-up.
      After one year, the mean difference (MD) of the 28 feet walking time was 0.00
      seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet
      walking time was -2.88 seconds, favouring the control group (95% CI -8.18 to
      2.42). Night splinting of the ankle did not significantly affect muscle force or
      range of movement about the ankle in a trial of 26 participants with Charcot
      Marie-Tooth disease. Improvements were observed in both the splinting and control
      groups. In a trial of 26 participants with Charcot-Marie-Tooth disease and 28
      participants with myotonic dystrophy, 24 weeks of strength training significantly
      improved six-metre timed walk in the Charcot-Marie-Tooth group compared to the
      control group (MD 0.70 seconds, favouring strength training, 95% CI 0.23 to
      1.17), but not in the myotonic dystrophy group (MD -0.20 seconds, favouring the
      control group, 95% CI -0.79 to 0.39). No significant differences were observed
      for the 50 metre timed walk in the Charcot-Marie-Tooth disease group (MD 1.90
      seconds, favouring the training group, 95% CI -0.29 to 4.09) or the myotonic
      dystrophy group (MD -0.80 seconds, favouring the control group, 95% CI -5.29 to
      3.69). In a trial of 65 participants with facioscapulohumeral muscular dystrophy,
      26 weeks of strength training did not significantly affect ankle strength. After
      one year, the mean difference in maximum voluntary isometric contraction was 
      0.43 kg, favouring the control group (95%CI -2.49 to 1.63) and the mean
      difference in dynamic strength was 0.44 kg, favouring the training group (95%CI 
      0.89 to 1.77). AUTHORS' CONCLUSIONS: Only one study, involving people with
      Charcot-Marie-Tooth disease, demonstrated a statistically significant positive
      effect of strength training. No effect of strength training was found in people
      with either myotonic dystrophy or facioscapulohumeral muscular dystrophy. Surgery
      had no significant effect in children with Duchenne muscular dystrophy and night
      splinting of the ankle had no significant effect in people with Charcot-Marie
      Tooth disease. More evidence generated by methodologically sound trials is
      required.

PMID- 19588349
TI  - Lidocaine for preventing postoperative sore throat.
AB  - BACKGROUND: Sore throat is a common side effect of general anaesthesia and is
      reported by between 30% and 70% of patients after tracheal intubation. The
      likelihood of a sore throat varies with the type, diameter, and cuff pressure of
      the endotracheal tube used. If intubation is essential, it may be helpful to give
      drugs prophylactically to alleviate postoperative sore throat. Local anaesthetics
      and steroids have been used for this purpose. OBJECTIVES: The objective of this
      review was to evaluate the effectiveness and any harms of topical and systematic
      lidocaine for the prevention of postoperative sore throat in adults undergoing
      endotracheal intubation as part of general anaesthesia. SEARCH STRATEGY: We
      searched CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (January 1966 to
      June 2007), and EMBASE (1980 to June 2007). We also contacted manufacturers and
      researchers in the field. SELECTION CRITERIA: We included randomized controlled
      trials of topical and systemic prophylactic lidocaine therapy versus control
      (using air or saline) that reported on the risk and severity of postoperative
      sore throat as an outcome. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted study
      authors for additional information, such as the risk of adverse effects. MAIN
      RESULTS: We included 1232 patients from 15 studies; 672 patients received topical
      or systemic lidocaine therapy and 560 patients were allocated to the control
      group. Both the topical and systemic lidocaine therapy significantly reduced the
      risk of postoperative sore throat (risk ratio (RR) 0.58; 95% confidence interval
      (CI) 0.41 to 0.82). To evaluate the severity of sore throat on a visual analogue
      scale (VAS), 219 patients received topical or systemic lidocaine therapy and 152
      patients were allocated to the control groups. The severity of sore throat was
      reduced (mean difference (MD) -11.9; 95% CI -16.44 to -7.32), an effect that
      neared statistical significance. The adverse effects of lidocaine were not
      reported in these studies. AUTHORS' CONCLUSIONS: Our systematic review
      establishes the effectiveness of topical and systemic lidocaine for the
      prevention of postoperative sore throat resulting from intubation. The risk and
      severity of postoperative sore throat tended to be reduced. The effect size of
      lidocaine appeared to be affected by drug concentration and route of
      administration; management of cuff pressure during anaesthesia; the included
      population; and the type of outcome measured.

PMID- 19588348
TI  - Valproate preparations for agitation in dementia.
AB  - BACKGROUND: Agitation affects up to 70% of older people with dementia. Valproic
      acid derivatives have been used for the past 10 years to control agitation in
      dementia, but no systematic review of the effectiveness of this treatment has
      been published to date. A systematic review of 2004 examined three randomised,
      placebo-controlled trials of the effect of valproate therapy on older people with
      dementia who were agitated. The review was updated (October 2008) to include two
      additional studies. OBJECTIVES: To determine whether evidence supports the use of
      valproate preparations in the treatment of agitation of people with dementia.
      SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive
      Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO,
      CINAHL and LILACS were searched on 7 February 2008 using the terms: valproic OR
      valproate OR divalproex* . The CDCIG Specialized Register contains records from
      all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO,
      CINAHL, LILACS) as well as from many trials databases and grey literature
      sources. SELECTION CRITERIA: Randomized, placebo-controlled trials with concealed
      allocation where agitation and dementia of participants were assessed DATA
      COLLECTION AND ANALYSIS: 1. Two reviewers extracted data from published trials 2.
      Odds ratios of average differences were calculated 3. Only "intention to treat"
      analyses were included 4. Analysis compared participants treated with valproic
      acid with controls MAIN RESULTS: Meta-analysis in 2004 of the pooled results was
      limited because of the following problems.In Porsteinsson 2001, although the
      physicians having direct responsibility for patient care were blinded, a non
      blinded physician, who had no direct contact with these physicians, adjusted
      divalproex sodium dosage on the basis of reports from blinded raters and from
      confidential laboratory reports. Therefore, because the physician who controlled
      therapy knew which patients were receiving divalproex, the trial did not satisfy
      the criterion of concealed allocation.In Tariot 2001, 54% of the treated patients
      dropped out compared with 29% of control patients. Of all treated patients, 22%
      dropped out because of adverse effects, and the study had to be discontinued
      prematurely.The third trial (Sival 2002) had a cross-over design. No results from
      the first phase of the study were available, and although the statistical section
      stated, "the t-test for independent samples is used to analyse the two-period
      cross-over trial", because the samples were not independent - they are the same
      patients in the treatment and placebo groups - a question must be raised about
      the correctness of the analyses.The valproate preparation used in the trials
      varied - one used short-acting sodium valproate, one long-acting divalproex
      sodium, and the third early-onset acting divalproex sodium. Average doses
      differed (480 mg/d - 1000 mg/d), as did duration of therapy (3 weeks - 6 weeks),
      and ways of evaluating patients and their response to therapy.A limited meta
      analysis, pooling the results concerning adverse effects (Porsteinsson 2001,
      Tariot 2001) revealed the following: sedation occurred more frequently in
      patients treated with valproic acid than in controls. Urinary tract infection was
      more common among patients treated with valproic acid than controls.An updated
      systematic review (October 2008) of two new studies (Tariot 2005, Herrmann 2007)
      applied meta-analysis to the effect of valproate on agitation in demented
      patients and also combined these studies with the earlier reports to examine
      adverse effects among valproate treated patients. Because the study of Herrmann
      et al involved a cross-over design, only those results from the first part of
      this study were included in the updated review.The new meta-analysis of pooled
      results showed no improvement of agitation among valproate treated patients,
      compared with controls, and showed an increase in adverse events (falls,
      infection, gastrointestinal disorders) among valproate treated patients. AUTHORS'
      CONCLUSIONS: The updated review corroborates the earlier findings that valproate
      preparations are ineffective in treating agitation among demented patients, and
      that valproate therapy is associated with an unacceptable rate of adverse
      effects. More research on the use of valproate preparations for agitation of
      people with dementia is needed. On the basis of current evidence, valproate
      therapy cannot be recommended for management of agitation in dementia.

PMID- 19588350
TI  - Antiviral agents for treatment of herpes simplex virus infection in neonates.
AB  - BACKGROUND: Herpes simplex virus (HSV) is a rare but serious neonatal pathogen.
      Prior to the availability of antiviral drugs the mortality associated with all
      but localised neonatal infection was high, with 85% of infants with disseminated
      HSV infection and 50% of infants with encephalitis dying by one year of age. The
      morbidity in the survivors of multiorgan infection was also high, with up to 50%
      experiencing long-term neurological sequelae. OBJECTIVES: To determine the effect
      of antiviral agents in the treatment of neonatal HSV infections on mortality,
      progression of disease and neurodevelopmental sequelae at approximately one year.
      The secondary objective was to assess the effect of antiviral agents on major
      complications associated with the use of these agents including nephrotoxicity
      and bone marrow suppression. SEARCH STRATEGY: Trials were identified by searching
      the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and
      reference lists of published trials. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials of antiviral therapy in infants less than one month
      of age with virologically proven HSV infection were included. DATA COLLECTION AND
      ANALYSIS: Data were extracted and the analyses performed independently by two
      review authors. Studies were analysed for methodological quality using the
      criteria of the Cochrane Neonatal Review Group. All data were analysed using
      RevMan 5.1. When possible, meta-analysis was performed to calculate typical
      relative risk, typical risk difference, along with their 95% confidence intervals
      (CI). MAIN RESULTS: Two eligible studies of a total of 273 infants were included.
      Both studies were randomized controlled trials. One study treated 63 infants with
      vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with
      aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with
      placebo (Whitley 1980), infants with all forms of neonatal HSV disease were
      included [disseminated disease, central nervous system (CNS) disease alone, and
      skin, eye and mouth (SEM) disease].There was no significant reduction in the risk
      of mortality when analyzed as an entire group; however, mortality was
      significantly reduced when data from infants with CNS disease or disseminated
      disease were combined. There was no difference in the rate of neurological
      abnormalities in survivors at one year when analyzed as an entire group or by
      disease category.There was no difference between aciclovir and vidarabine
      (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing
      disease progression, in reducing the incidence of neurological abnormality at one
      year, or in the incidence of drug-induced renal or bone marrow toxicity. In
      infants with SEM disease, there was no significant difference in neurological
      outcome with aciclovir compared vidarabine treatment. Both drugs were well
      tolerated in the newborn period. AUTHORS' CONCLUSIONS: There is insufficient
      trial evidence to evaluate the effects of antiviral agents with controls or with
      each other. The rarity of the condition makes effectively powered clinical trials
      difficult to perform. The efficacy of newer antiviral agents with better
      bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal
      disease needs to be evaluated in randomised trials. The efficacy of oral
      formulations need to be evaluated as they may be useful for infants with skin,
      eye or mouth HSV disease or in the treatment of infants with recurrences after
      the neonatal period.

PMID- 19588351
TI  - HMG CoA reductase inhibitors (statins) for dialysis patients.
AB  - BACKGROUND: Cardiovascular disease accounts for more than half the number of
      deaths among dialysis patients. The role of HMG CoA reductase inhibitors
      (statins) in the treatment of dyslipidaemia in dialysis patients is unclear and
      their safety has not been established. OBJECTIVES: To assess the benefits and
      harms of statins in peritoneal dialysis (PD) and haemodialysis patients (HD).
      SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled trials (CENTRAL, in The Cochrane Library), the Cochrane Renal Group's
      specialised register and handsearched reference lists of textbooks, articles and
      scientific proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      and quasi-RCTs comparing statins with placebo, no treatment or other
      hypolipidaemic agents in dialysis patients. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed study quality and extracted data. Statistical
      analyses were performed using the random effects model after testing for
      heterogeneity. The results were expressed as mean difference (MD) for continuous
      outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence
      intervals (CI). MAIN RESULTS: Fourteen studies (2086 patients) compared statins
      versus placebo or other lipid lowering agents. Compared to placebo, statins did
      not decrease all-cause mortality (10 studies, 1884 patients; RR 0.95, 95% CI 0.86
      to 1.06) or cardiovascular mortality (9 studies, 1839 patients: RR 0.96, 95% CI
      0.65 to 1.40). There was a lower incidence of nonfatal cardiovascular events with
      statins compared to placebo in haemodialysis patients (1 study, 1255 patients; RR
      0.86, 95% CI 0.74 to 0.99). Compared with placebo, statin use was associated with
      a significantly lower end of treatment average total cholesterol (14 studies,
      1823 patients; MD -42.61 mg/dL, 95% CI -53.38 to -31.84), LDL cholesterol (13
      studies, 1801 patients; MD -43.06 mg/dL, 95% CI -53.78 to -32.35) and
      triglycerides (14 studies, 1823 patients: MD -24.01 mg/dL, 95% CI -47.29 to 
      0.72). There was similar occurrence of rhabdomyolysis and elevated liver function
      tests with statins in comparison to placebo. AUTHORS' CONCLUSIONS: Statins
      decreased cholesterol levels in dialysis patients similar to that of the general
      population. With the exception of one study, studies were of short duration and
      therefore the efficacy of statins in decreasing the mortality rate is still
      unclear. Statins appear to be safe in this high-risk population. Ongoing studies
      should provide more insight about the efficacy of statins in reducing mortality
      rates in dialysis patients.

PMID- 19588352
TI  - Treatment for avascular necrosis of bone in people with sickle cell disease.
AB  - BACKGROUND: Avascular necrosis of bone is a frequent and severe complication of
      sickle cell disease (SCD) and its treatment is not standardised. OBJECTIVES: To
      determine the impact of any surgical procedure compared with other surgical
      interventions or non-surgical procedures, on avascular necrosis of bone in people
      with SCD in terms of efficacy and safety. SEARCH STRATEGY: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials
      Register, comprising references identified from comprehensive electronic database
      searches and handsearches of relevant journals and abstract books of conference
      proceedings. Additional trials were sought from the reference lists of papers
      identified by the search strategy.Most recent search: 27 March 2009. SELECTION
      CRITERIA: Randomised clinical trials comparing specific therapies for avascular
      necrosis of bone in people with SCD. DATA COLLECTION AND ANALYSIS: Each author
      independently extracted data and assessed trial quality. Since only one trial was
      identified, meta-analysis was not possible. MAIN RESULTS: One trial (46
      participants) was eligible for inclusion. After randomisation eight participants
      were withdrawn, mainly because they declined to participate in the trial. Data
      were analysed for 38 participants at the end of the trial. After a mean follow up
      of three years, hip core decompression and physical therapy did not show clinical
      improvement when compared with physical therapy alone using the score from the
      original trial (an improvement of 18.1 points for those treated with intervention
      therapy versus an improvement of 15.7 points with control therapy). There was no
      significant statistical difference between groups regarding major complications
      (hip pain, relative risk (RR) 0.95 (95% confidence interval (CI) 0.56 to 1.60;
      vaso-occlusive crises, RR 1.14 (95% CI 0.72 to 1.80); and acute chest syndrome,
      RR 1.06 (95% CI 0.44 to 2.56)). This trial did not report results on mortality or
      quality of life. AUTHORS' CONCLUSIONS: We found no evidence that adding hip core
      decompression to physical therapy achieves clinical improvement in people with
      SCD with avascular necrosis of bone compared to physical therapy alone. However,
      we highlight that our conclusion is based on one trial with high attrition rates.
      Further randomised controlled trials are necessary to evaluate the role of hip
      core depression for this clinical condition. Endpoints should focus on
      participants' subjective experience (e.g. quality of life and pain) as well as
      more objective 'time-to-event' measures (e.g. mortality, survival, hip
      longevity). The availability of participants to allow adequate trial power will
      be a key consideration for endpoint choice.

PMID- 19588353
TI  - Treatment blood pressure targets for hypertension.
AB  - BACKGROUND: When treating elevated blood pressure, doctors need to know what
      blood pressure (BP) target they should try to achieve. The standard of clinical
      practice for some time has been </= 140 - 160/ 90 - 100 mmHg. New guidelines are
      recommending BP targets lower than this standard. It is not known whether
      attempting to achieve targets lower than the standard reduces mortality and
      morbidity. OBJECTIVES: To determine if lower BP targets (</= 135/85 mmHg) are
      associated with reduction in mortality and morbidity as compared with standard BP
      targets (</= 140-160/ 90-100 mmHg). SEARCH STRATEGY: Electronic search of MEDLINE
      (1966-2008), EMBASE (1980-2008), and CENTRAL (up to June 2008); references from
      review articles, clinical guidelines, and clinical trials. SELECTION CRITERIA:
      Randomized controlled trials comparing patients randomized to lower or to
      standard BP targets and providing data on any of the primary outcomes below. DATA
      COLLECTION AND ANALYSIS: Two reviewers (JAA, MIP) independently assessed the
      included trials and data entry. Primary outcomes were total mortality; total
      serious adverse events; total cardiovascular events; myocardial infarction,
      stroke, congestive heart failure and end stage renal disease. Secondary outcomes
      were achieved mean systolic and diastolic BP and withdrawals due to adverse
      effects. MAIN RESULTS: No trials comparing different systolic BP targets were
      found. Seven trials (22,089 subjects) comparing different diastolic BP targets
      were included. Despite a -4/-3 mmHg greater achieved reduction in
      systolic/diastolic BP, p< 0.001, attempting to achieve "lower targets" instead of
      "standard targets" did not change total mortality (RR 0.92, 95% CI 0.86-1.15),
      myocardial infarction (RR 0.90, 95% CI 0.74-1.09), stroke (RR 0.99, 95% CI 0.79
      1.25) , congestive heart failure (RR 0.88, 95% CI 0.59-1.32), major
      cardiovascular events (RR 0.94, 95% CI 0.83-1.07), or end-stage renal disease (RR
      1.01, 95% CI 0.81-1.27). The net health effect of lower targets cannot be fully
      assessed due to lack of information regarding all total serious adverse events
      and withdrawals due to adverse effects in 6 of 7 trials. A sensitivity analysis
      in diabetic patients and in patients with chronic renal disease also did not show
      a reduction in any of the mortality and morbidity outcomes with lower targets as
      compared to standard targets. AUTHORS' CONCLUSIONS: Treating patients to lower
      than standard BP targets, </=140-160/90-100 mmHg, does not reduce mortality or
      morbidity. Because guidelines are recommending even lower targets for diabetes
      mellitus and chronic renal disease, we are currently conducting systematic
      reviews in those groups of patients.

PMID- 19588354
TI  - Exercise for depression.
AB  - BACKGROUND: Depression is a common and important cause of morbidity and mortality
      worldwide. Depression is commonly treated with antidepressants and/or
      psychotherapy, but some people may prefer alternative approaches such as
      exercise. There are a number of theoretical reasons why exercise may improve
      depression. OBJECTIVES: To determine the effectiveness of exercise in the
      treatment of depression. SEARCH STRATEGY: We searched Medline, Embase, Sports
      Discus, PsycINFO, the Cochrane Controlled Trials Register, and the Cochrane
      Database of Systematic Reviews for eligible studies in March 2007. In addition,
      we hand-searched several relevant journals, contacted experts in the field,
      searched bibliographies of retrieved articles, and performed citation searches of
      identified studies. We also searched www.controlled-trials.com in May 2008.
      SELECTION CRITERIA: Randomised controlled trials in which exercise was compared
      to standard treatment, no treatment or a placebo treatment in adults (aged 18 and
      over) with depression, as defined by trial authors. We excluded trials of post
      natal depression. DATA COLLECTION AND ANALYSIS: We calculated effect sizes for
      each trial using Cohen's method and a standardised mean difference (SMD) for the
      overall pooled effect, using a random effects model. Where trials used a number
      of different tools to assess depression, we included the main outcome measure
      only in the meta-analysis. MAIN RESULTS: Twenty-eight trials fulfilled our
      inclusion criteria, of which 25 provided data for meta-analyses. Randomisation
      was adequately concealed in a minority of studies, most did not use intention to
      treat analyses and most used self-reported symptoms as outcome measures. For the
      23 trials (907 participants) comparing exercise with no treatment or a control
      intervention, the pooled SMD was -0.82 (95% CI -1.12, -0.51), indicating a large
      clinical effect. However, when we included only the three trials with adequate
      allocation concealment and intention to treat analysis and blinded outcome
      assessment, the pooled SMD was -0.42 (95% CI -0.88, 0.03) i.e. moderate, non
      significant effect. The effect of exercise was not significantly different from
      that of cognitive therapy. There was insufficient data to determine risks and
      costs. AUTHORS' CONCLUSIONS: Exercise seems to improve depressive symptoms in
      people with a diagnosis of depression, but when only methodologically robust
      trials are included, the effect sizes are only moderate and not statistically
      significant. Further, more methodologically robust trials should be performed to
      obtain more accurate estimates of effect sizes, and to determine risks and costs.
      Further systematic reviews could be performed to investigate the effect of
      exercise in people with dysthymia who do not fulfil diagnostic criteria for
      depression.

PMID- 19588355
TI  - Combined oral contraceptive pills for treatment of acne.
AB  - BACKGROUND: Acne is a common skin disorder among women. Although no uniform
      approach to the management of acne exists, combination oral contraceptives
      (COCs), which contain an estrogen and a progestin, often are prescribed for
      women. OBJECTIVES: To determine the effectiveness of combined oral contraceptives
      (COCs) for the treatment of facial acne compared to placebo or other active
      therapies. SEARCH STRATEGY: We searched for randomized controlled trials of COCs
      and acne in the computerized databases of the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, and LILACS. We also
      searched for clinical trials in ClinicalTrials.gov and the International Clinical
      Trials Registry Platform (ICTRP). We wrote to authors of identified trials to
      seek any unpublished or published trials that we might have missed. SELECTION
      CRITERIA: All randomized controlled trials reported in any language that compared
      the effectiveness of a COC containing an estrogen and a progestin to placebo or
      another active therapy for acne in women were eligible. DATA COLLECTION AND
      ANALYSIS: We extracted data on total and specific (i.e., open or closed
      comedones, papules, pustules and nodules) facial lesion counts; acne severity
      grades; global assessments by the clinician or the participant and
      discontinuation due to adverse events. Data were entered and analyzed in RevMan.
      MAIN RESULTS: The search yielded 25 trials: 7 placebo-controlled trials made 4
      different comparisons, 17 trials made 13 comparisons between 2 different COC
      regimens, and 1 additional trial compared a COC to an antibiotic. COCs reduced
      acne lesion counts, severity grades and self-assessed acne compared to placebo.
      Differences in the comparative effectiveness of COCs containing varying progestin
      types and dosages, though, were less clear. COCs that contained chlormadinone
      acetate or cyproterone acetate improved acne better than levonorgestrel, although
      this apparent advantage was based on limited data. A COC with cyproterone acetate
      might result in better acne outcomes than one with desogestrel; however, the
      three studies comparing these COCs produced conflicting results. Likewise,
      levonorgestrel showed a slight improvement over desogestrel in acne outcomes in
      one trial, but a second trial found the COC groups were similar. AUTHORS'
      CONCLUSIONS: The four COCs evaluated in placebo-controlled trials are effective
      in reducing inflammatory and non-inflammatory facial acne lesions. Few important
      differences were found between COC types in their effectiveness for treating
      acne. How COCs compare to alternative acne treatments is unknown since limited
      data were available regarding this question.

PMID- 19588356
TI  - Endothelin receptor antagonists for pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension is a devastating disease, which leads
      to right heart failure and premature death. Recent evidence suggests that
      endothelin receptor antagonists may be promising drugs in the treatment of
      pulmonary arterial hypertension. OBJECTIVES: To evaluate the efficacy of
      endothelin receptor antagonists in pulmonary arterial hypertension. SEARCH
      STRATEGY: We searched CENTRAL (Cochrane Central Register of Controlled Trials),
      MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are
      current as of Februray 2008. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) or quasi-randomised controlled trials involving patients with pulmonary
      arterial hypertension. DATA COLLECTION AND ANALYSIS: Five review authors
      independently selected studies, assessed study quality and extracted data. MAIN
      RESULTS: Five new studies have been added to this updated review, which now
      includes 11 randomised controlled trials involving 1457 patients. All the trials
      were of relatively short duration (12 weeks to 6 months). After treatment,
      patients treated with endothelin receptor antagonists could walk on average 33.7
      metres (95% confidence interval [CI] 24.9 to 42.5 metres) further than those
      treated with placebo in a 6 minute walk test. Endothelin receptor antagonists
      improved more patients' World Health Organization/New York Heart Association
      (WHO/NYHA) functional class status than placebo (odds ratio [OR] 1.6; 95%
      confidence interval [CI] 1.2 to 2.1), and reduced the odds of functional class
      deterioration compared to placebo (OR 0.26; 95% CI 0.16 to 0.42 ). There was a
      trend for endothelin receptor antagonists to reduce mortality (OR 0.48; 95% CI
      0.21 to 1.09), and limited data suggest that endothelin receptor antagonists
      improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic
      patients. Hepatic toxicity was not common, and endothelin receptor antagonists
      were well tolerated in this population. AUTHORS' CONCLUSIONS: Endothelin receptor
      antagonists can increase exercise capacity, improve WHO/NYHA functional class,
      prevent WHO/NYHA functional class deterioration, reduce dyspnoea and improve
      cardiopulmonary haemodynamic variables in patients with pulmonary arterial
      hypertension with WHO/NYHA functional class II and III. However, there was only a
      trend towards endothelin receptor antagonists reducing mortality in patients with
      pulmonary arterial hypertension. Efficacy data are strongest in those with
      idiopathic pulmonary hypertension.

PMID- 19588357
TI  - Thrombolytic therapy for pulmonary embolism.
AB  - BACKGROUND: Thrombolytic therapy is usually reserved for patients with clinically
      serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic
      agents may dissolve blood clots more rapidly than heparin and might reduce the
      death rate associated with PE. However, there are still concerns about the
      possible risk of adverse effects of thrombolytic therapy, such as major or minor
      haemorrhages. This is an update of a Cochrane review first published in 2006.
      OBJECTIVES: To assess the effectiveness and safety of thrombolytic therapy in
      patients with acute PE. SEARCH STRATEGY: For this update the Cochrane Peripheral
      Vascular Diseases Review Group searched their Specialised Register (last searched
      April 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in
      The Cochrane Library (last searched Issue 2, 2009). We also searched individual
      trial collections and private databases, along with bibliographies of relevant
      articles. Relevant medical journals were handsearched. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) that compared thrombolytic therapy with
      placebo or heparin or surgical intervention in patients with acute PE. We did not
      include trials comparing two different thrombolytic agents or different doses of
      the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two authors (DB and WQ)
      assessed the eligibility and quality of trials and extracted data. MAIN RESULTS:
      We included eight trials, with a total of 679 patients, in this review. Results
      between thrombolytics compared with heparin alone or placebo and heparin were
      similar in terms of: a) death rate: odds ratio (OR) 0.89; 95% confidence interval
      (CI) 0.45 to 1.78; b) recurrence of pulmonary embolism: OR 0.63; 95% CI 0.33 to
      1.20; c) major haemorrhagic events: OR 1.61; 95% CI 0.91 to 2.86; d) minor
      haemorrhagic events: OR 1.98; 95% CI 0.68 to 5.75.We found no trials comparing
      thrombolytic therapy to surgical intervention.Using recombinant tissue-type
      plasminogen activator (rt-PA) and heparin together compared to heparin alone
      appeared to reduce the need for further treatment for in-hospital events (OR
      0.35; 95% CI 0.17 to 0.71).Thrombolytics improved haemodynamic outcomes,
      perfusion lung scanning, pulmonary angiogram assessment and echocardiograms to a
      greater extent than heparin alone. AUTHORS' CONCLUSIONS: Based on the limited
      evidence found we cannot conclude whether thrombolytic therapy is better than
      heparin for pulmonary embolism. More double-blind RCTs, with subgroup analysis of
      patients presenting with haemodynamically stable acute pulmonary embolism
      compared to those patients with a haemodynamic unstable condition, are required.

PMID- 19588358
TI  - Antibiotics for treating chronic osteomyelitis in adults.
AB  - BACKGROUND: Chronic osteomyelitis is generally treated with antibiotics and
      surgical debridement but can persist intermittently for years with frequent
      therapeutic failure. Despite advances in both antibiotics and surgical treatment,
      the long-term recurrence rate remains at approximately 20% to 30%. OBJECTIVES: To
      determine the effects of different systemic antibiotic treatment regimens for
      treating chronic osteomyelitis in adults. SEARCH STRATEGY: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (October 2008),
      the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008,
      Issue 3), MEDLINE (January 1966 to October 2008), EMBASE (January 1980 to October
      2008), LILACS (October 2008) and reference lists of relevant articles. SELECTION
      CRITERIA: Randomised or quasi-randomised controlled trials addressing the effects
      of different antibiotic treatments given after surgical debridement for chronic
      osteomyelitis in adults. DATA COLLECTION AND ANALYSIS: Two authors independently
      screened papers for inclusion, extracted data and appraised the quality of
      included trials. Where appropriate, we pooled data using the fixed-effect model.
      MAIN RESULTS: We included eight small trials (257 participants in total, with
      data available from 228). Study quality was often inadequate: in particular,
      concealment of allocation was not confirmed and there was an absence of blinding
      of outcome assessment. The antibiotic regimens, duration of treatment and follow
      up varied between trials. Five trials compared oral versus parenteral
      antibiotics. There was no statistically significant difference between the two
      groups in the remission rate 12 or more months after treatment (risk ratio 0.94,
      95% confidence interval 0.78 to 1.13; 3 trials). Antibiotic treatment for
      osteomyelitis was associated with moderate or severe adverse events in 4.8% of
      patients allocated oral antibiotics and 15.5% patients allocated parenteral
      antibiotics (risk ratio: 0.40, 95% confidence interval 0.13 to 1.22; 4 trials).
      Single trials with very few participants found no statistical significant
      differences for remission or adverse events for the following three comparisons:
      parenteral plus oral versus parenteral only administration; two oral antibiotic
      regimens; and two parenteral antibiotic regimens. No trials compared different
      durations of antibiotic treatment for chronic osteomyelitis, or adjusted the
      remission rate for bacteria species or severity of disease. AUTHORS' CONCLUSIONS:
      Limited evidence suggests that the method of antibiotic administration (oral
      versus parenteral) does not affect the rate of disease remission if the bacteria
      are sensitive to the antibiotic used. However, this and the lack of statistically
      significant differences in adverse effects need confirmation. No or insufficient
      evidence exists for other aspects of antibiotic therapy for chronic
      osteomyelitis.

PMID- 19588359
TI  - The 'WHO Safe Communities' model for the prevention of injury in whole
      populations.
AB  - BACKGROUND: The World Health Organization (WHO) 'safe communities' approach to
      injury prevention has been embraced around the world as a model for co-ordinating
      community efforts to enhance safety and reduce injury. Approximately 150
      communities throughout the world have formal 'Safe Communities' designation. It
      is of public health interest to determine to what degree the model is successful,
      and whether it reduces injury rates. This Cochrane Review is an update of a
      previous published version. OBJECTIVES: To determine the effectiveness of the WHO
      Safe Communities model to prevent injury in whole populations. SEARCH STRATEGY:
      Our search included CENTRAL, MEDLINE and EMBASE, PsycINFO, ISI Web of Science:
      Social Sciences Citation Index (SSCI) and ZETOC. We handsearched selected
      journals and contacted key people from each WHO Safe Community. The last search
      was December 2008. SELECTION CRITERIA: Two authors independently screened studies
      for inclusion. Included studies were those conducted within a WHO Safe Community
      that reported changes in population injury rates within the community compared to
      a control community. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data. Meta-analysis was not appropriate due to the heterogeneity of the
      included studies. MAIN RESULTS: We included evaluations for 21 communities from
      five countries in two geographical regions in the world: Austria, Sweden and
      Norway, and Australia and New Zealand. Although positive results were reported
      for some communities, there was no consistent relationship between being a WHO
      designated Safe Community and subsequent changes in observed injury rates.
      AUTHORS' CONCLUSIONS: There is marked inconsistency in the results of the studies
      included in this systematic review. While the frequency of injury in some study
      communities did reduce following their designation as a WHO Safe Community, there
      remains insufficient evidence from which to draw definitive conclusions regarding
      the effectiveness of the model.The lack of consistency in results may be due to
      the heterogeneity of the approaches to implementing the model, varying efficacy
      of activities and strategies, varying intensity of implementation and
      methodological limitations in evaluations. While all communities included in the
      review fulfilled the WHO Safe Community criteria, these criteria were too general
      to prescribe a standardised programme of activity or evaluation
      methodology.Adequate documentation describing how various Safe Communities
      implemented the model was limited, making it unclear which factors affected
      success. Where a reduction in injury rates was not reported, lack of information
      makes it difficult to distinguish whether this was due to problems with the model
      or with the way in which it was implemented.

PMID- 19588360
TI  - Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer is diagnosed in 4500 women in the UK each
      year of whom 1700 will ultimately die of their disease. Ten to fifteen percent of
      all cases are diagnosed early when there is still a good possibility for cure.
      The treatment of early stage disease involves surgery to remove disease often
      followed by chemotherapy. The largest clinical trials of this adjuvant therapy
      show an overall survival (OS) advantage with adjuvant platinum based chemotherapy
      but the precise role of this treatment in sub-groups of patients with differing
      prognoses needs to be defined. OBJECTIVES: To systematically review the evidence
      for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine;
      firstly whether there is a survival advantage of this treatment over the policy
      of observation following surgery with chemotherapy reserved for treatment of
      disease recurrence, and secondly; to determine if clinical sub-groups of
      differing prognosis based on histological sub-type or completeness of surgical
      staging, have more or less to gain from chemotherapy following initial surgery.
      SEARCH STRATEGY: An electronic search was performed using the Cochrane
      Gynaecological Cancer Specialised Register, Cochrane Central Register of
      Controlled Trials (CENTRAL, Issue 2, 2008), MEDLINE (1966 to 2008), EMBASE (1980
      to 2008) and CancerLit. The search strategy was developed using free text and
      medical subject headings (MESH). SELECTION CRITERIA: The review authors selected
      those clinical trials that met the inclusion criteria set out based on the
      populations, interventions, comparisons and outcome measures. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed trial
      quality. Disagreements were resolved by discussion with a third review author.
      Random effects meta-analyses and sub-group analyses were conducted. MAIN RESULTS:
      Five randomised controlled trials (RCTs), enrolling 1277 women, with 46 to 110
      months follow-up, met the inclusion criteria. These trials had low risk of bias.
      Meta-analysis of three trials with adequate data, assessing 1008 women, indicated
      that women who received adjuvant platinum-based chemotherapy had better overall
      survival (OS) than those who did not (hazard ratio (HR) 0.71; 95% CI 0.53 to
      0.93). Likewise, meta-analysis of four trials with adequate data, assessing 1170
      women, indicated that women who received adjuvant chemotherapy had better
      progression-free survival (PFS) than those who did not (HR 0.67; 95% CI 0.53 to
      0.84). The trials included in these meta-analyses gave consistent estimates of
      the effects of chemotherapy.Sub-group analysis suggested that women who had
      optimal surgical staging of their disease were unlikely to benefit from adjuvant
      chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37) whereas those who had sub
      optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85). One trial showed a
      benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95%
      CI 0.32 to 0.72) but not among those at low risk (HR for OS 0.95; 95% CI 0.54 to
      1.66). However, these sub-group findings could be due to chance. AUTHORS'
      CONCLUSIONS: Adjuvant platinum based chemotherapy is effective in prolonging the
      survival of the majority of patients who are assessed as having early stage
      epithelial ovarian cancer. However, even given the limits of sub-group analyses,
      there is strong evidence that optimal surgical staging identifies patients who
      have either little or nothing to gain from adjuvant chemotherapy. Taken together
      with the lack of a survival advantage seen in patients with "low-risk" cancers in
      the ICON1 trial, it appears safe to withhold adjuvant chemotherapy from optimally
      staged patients with well differentiated tumours.

PMID- 19588362
TI  - Green tea (Camellia sinensis) for the prevention of cancer.
AB  - BACKGROUND: Tea is one of the most commonly consumed beverages worldwide. Teas
      from the plant Camellia sinensis can be grouped into green, black and oolong tea.
      Cross-culturally tea drinking habits vary. Camellia sinensis contains the active
      ingredient polyphenol, which has a subgroup known as catechins. Catechins are
      powerful antioxidants. It has been suggested that green tea polyphenol may
      inhibit cell proliferation and observational studies have suggested that green
      tea may have cancer-preventative effects. OBJECTIVES: To critically assess any
      associations between green tea consumption and the risk of cancer incidence and
      mortality. SEARCH STRATEGY: We searched eligible studies up to January 2009 in
      the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      Amed, CancerLit, Psych INFO and Phytobase and reference lists of previous reviews
      and included studies. SELECTION CRITERIA: We included all prospective, controlled
      interventional studies and observational studies, which either assessed the
      associations between green tea consumption and risk of cancer incidence or that
      reported on cancer mortality. DATA COLLECTION AND ANALYSIS: At least two review
      authors independently applied the study criteria, extracted data and assessed
      methodological quality of studies. Due to the nature of included studies, which
      were mainly epidemiological, results were summarised descriptively according to
      cancer diagnosis. MAIN RESULTS: Fifty-one studies with more than 1.6 million
      participants were included. Twenty-seven of them were case-control studies, 23
      cohort studies and one randomised controlled trial (RCT).Twenty-seven studies
      tried to establish an association between green tea consumption and cancer of the
      digestive tract, mainly of the upper gastrointestinal tract, five with breast
      cancer, five with prostate cancer, three with lung cancer, two with ovarian
      cancer, two with urinary bladder cancer one with oral cancer, three further
      studies included patients with various cancer diagnoses.The methodological
      quality was measured with the Newcastle-Ottawa scale (NOS). The 9 nested case
      control studies within prospective cohorts were of high methodological quality,
      13 of medium, and 1 of low. One retrospective case-control study was of high
      methodological quality and 21 of medium and 5 of low.Results from studies
      assessing associations between green tea and risk of digestive tract cancer
      incidence were highly contradictory. There was limited evidence that green tea
      could reduce the incidence of liver cancer. The evidence for esophageal, gastric,
      colon, rectum, and pancreatic cancer was conflicting. In prostate cancer,
      observational studies with higher methodological quality and the only included
      RCT suggested a decreased risk in men consuming higher quantities green tea or
      green tea extracts. However, there was limited to moderate evidence that the
      consumption of green tea reduced the risk of lung cancer, especially in men, and
      urinary bladder cancer or that it could even increase the risk of the latter.
      There was moderate to strong evidence that green tea consumption does not
      decrease the risk of dying from gastric cancer. There was limited moderate to
      strong evidence for lung, pancreatic and colorectal cancer. AUTHORS' CONCLUSIONS:
      There is insufficient and conflicting evidence to give any firm recommendations
      regarding green tea consumption for cancer prevention. The results of this
      review, including its trends of associations, need to be interpreted with caution
      and their generalisability is questionable, as the majority of included studies
      were carried out in Asia (n = 47) where the tea drinking culture is pronounced.
      Desirable green tea intake is 3 to 5 cups per day (up to 1200 ml/day), providing
      a minimum of 250 mg/day catechins. If not exceeding the daily recommended
      allowance, those who enjoy a cup of green tea should continue its consumption.
      Drinking green tea appears to be safe at moderate, regular and habitual use.

PMID- 19588361
TI  - Electronic retrieval of health information by healthcare providers to improve
      practice and patient care.
AB  - BACKGROUND: The movement towards evidence-based practice makes explicit the need
      for access to current best evidence to improve health. Advances in electronic
      technologies have made health information more available, but does availability
      affect the rate of use of evidence in practice? OBJECTIVES: To assess the
      effectiveness of interventions intended to provide electronic retrieval (access
      to information) to health information by healthcare providers to improve practice
      and patient care. SEARCH STRATEGY: We obtained studies from computerized searches
      of multiple electronic bibliographic databases, supplemented by checking
      reference lists, and consultation with experts. SELECTION CRITERIA: Randomized
      controlled trials (RCTs) including cluster randomized trials (CRCTs), controlled
      clinical trials (CCT), and interrupted time series analyses (ITS) of any language
      publication status examining interventions of effectiveness of electronic
      retrieval of health information by healthcare providers. DATA COLLECTION AND
      ANALYSIS: Duplicate relevancy screening of searches, data abstraction and risk of
      bias assessment was undertaken. MAIN RESULTS: We found two studies that examined
      this question. Neither study found any changes in professional behavior following
      an intervention that facilitated electronic retrieval of health information.
      There was some evidence of improvements in knowledge about the electronic sources
      of information reported in one study. Neither study assessed changes in patient
      outcomes or the costs of provision of the electronic resource and the
      implementation of the recommended evidence-based practices. AUTHORS' CONCLUSIONS:
      Overall there was insufficient evidence to support or refute the use of
      electronic retrieval of healthcare information by healthcare providers to improve
      practice and patient care.

PMID- 19588363
TI  - Vision screening for amblyopia in childhood.
AB  - BACKGROUND: Amblyopia is a reversible deficit of vision that has to be treated
      within the sensitive period for visual development. Screening programmes have
      been set up to detect this largely asymptomatic condition and refer children for
      treatment while an improvement in vision is still possible. The value of such
      programmes and the optimum protocol for administering them remain controversial.
      OBJECTIVES: The objective of this review was to evaluate the effectiveness of
      vision screening in reducing the prevalence of amblyopia. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 3, 2008), MEDLINE (January 1950 to August 2008) and EMBASE (January 1947 to
      August 2008). The electronic databases were last searched on 15 August 2008. No
      language restrictions were placed on these searches. No handsearching was done.
      SELECTION CRITERIA: We planned to analyse data from randomised controlled trials
      and cluster-randomised trials comparing the prevalence of amblyopia in screened
      versus unscreened populations. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed study abstracts identified by the electronic searches.
      Full text copies of appropriate studies were obtained and, where necessary,
      authors were contacted. No data were available for analysis and no meta-analysis
      was performed. MAIN RESULTS: Despite the large amount of literature available
      regarding vision screening no trials designed to compare the prevalence of
      amblyopia in screened versus unscreened populations were found. AUTHORS'
      CONCLUSIONS: The lack of data from randomised controlled trials makes it
      difficult to analyse the impact of existing screening programmes on the
      prevalence of amblyopia. The absence of such evidence cannot be taken to mean
      that vision screening is not beneficial; simply that this intervention has not
      yet been tested in robust trials. To facilitate such trials normative data on age
      appropriate vision tests need to be available and a consensus reached regarding
      the definition of amblyopia. In addition, the consequences of living with
      untreated amblyopia have yet to be quantified and a cost-benefit analysis carried
      out.

PMID- 19588364
TI  - Advocacy interventions to reduce or eliminate violence and promote the physical
      and psychosocial well-being of women who experience intimate partner abuse.
AB  - BACKGROUND: Intimate partner abuse is common in all societies and damages the
      health of survivors and their children in the short and long term. Advocacy may
      decrease the impact of this abuse on women's health. OBJECTIVES: To assess the
      effects of advocacy interventions conducted within or outside of health care
      settings on women who have experienced intimate partner abuse. SEARCH STRATEGY:
      We searched: CENTRAL and DARE (Cochrane Library Issue 3, 2008), MEDLINE (1966 to
      31/7/08), EMBASE (1980 to 2008 week 30), and 11 other databases, to end July
      2008. We also searched relevant websites, reference lists and forward citation
      tracking of included studies, and handsearched six key journals. We contacted
      principal investigators and experts in the field. SELECTION CRITERIA: Randomised
      controlled trials comparing advocacy interventions for women with experience of
      intimate partner abuse against usual care. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and undertook data extraction. For
      binary outcomes we calculated a standardised estimation of the odds ratio (OR)
      and for continuous data we calculated either a standardised mean difference (SMD)
      or a weighted mean difference (WMD), both with a 95% confidence interval. MAIN
      RESULTS: We included ten trials involving 1527 participants. The studies were
      heterogeneous in respect of: intensity of advocacy, outcome measures and duration
      of follow-up (immediately post-intervention to three years), permitting meta
      analysis for only a minority of outcomes. Intensive advocacy (12 hours or more
      duration) may help terminate physical abuse in women leaving domestic violence
      shelters or refuges at 12-24 months follow-up (OR 0.43, 95% CI 0.23 to 0.80), but
      not at up to 12 months follow-up. The evidence indicates that intensive advocacy
      may improve quality of life at up to 12 months follow-up, but the confidence
      intervals included zero (WMD 0.23, 95% CI 0.00 to 0.46). Depression did not
      improve following intensive advocacy at up to 12 months follow-up (WMD -0.05, 95%
      CI -0.19 to 0.09), nor did psychological distress (SMD -0.16, 95% CI -0.39 to
      0.06). Only two meta-analyses of brief advocacy interventions (less than 12 hours
      duration) were possible; an increased use of safety behaviours was consistent
      with the receipt of brief advocacy both at up to 12 months (WMD 0.60, 95% CI 0.14
      to 1.06) and at 12-24 months (WMD 0.48, 95% CI 0.04 to 0.92) follow up. AUTHORS'
      CONCLUSIONS: Based on the evidence reviewed, it is possible that intensive
      advocacy for women recruited in domestic violence shelters or refuges reduces
      physical abuse one to two years after the intervention but we do not know if it
      has a beneficial effect on their quality of life and mental health. Similarly,
      there is insufficient evidence to show if less intensive interventions in
      healthcare settings for women who still live with the perpetrators of violence
      are effective.

PMID- 19588365
TI  - Interventions for preventing and treating kidney disease in Henoch-Schonlein
      Purpura (HSP).
AB  - BACKGROUND: To determine the benefits and harms of therapies used to prevent or
      treat kidney disease in Henoch-Schonlein Purpura (HSP). OBJECTIVES: To evaluate
      the benefits and harms of different agents (used singularly or in combination)
      compared with placebo or no treatment or another agent for the prevention or
      treatment of kidney disease in patients with HSP. SEARCH STRATEGY: Randomised
      controlled trials (RCTs) and quasi-RCTs were identified from the Cochrane Renal
      Group's specialised register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE and EMBASE using optimally sensitive search strategies
      combined with search terms for HSP. SELECTION CRITERIA: RCTs comparing any
      intervention used to prevent or treat kidney disease in HSP compared with
      placebo, no treatment or other agents were included. DATA COLLECTION AND
      ANALYSIS: Three authors independently assessed trial quality and extracted data
      from each study. Statistical analyses were performed using the random effects
      model and the results were expressed as risk ratio (RR) for dichotomous outcomes
      and mean difference (MD) for continuous outcomes with 95% confidence intervals
      (CI). MAIN RESULTS: Ten studies (1230 children) were identified. There was no
      significant difference in the risk of persistent kidney disease at six months (3
      studies, 379 children: RR 0.51, 95% CI 0.24 to 1.11) and 12 months (3 studies,
      498 children: RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14
      to 28 days at presentation of HSP compared with placebo or supportive treatment.
      In children with severe kidney disease, there was no significant difference in
      the risk of persistent kidney disease with cyclophosphamide compared with
      supportive treatment (1 study, 56 children: RR 1.07, 95% CI 0.65 to 1.78) and
      with cyclosporin compared with methylprednisolone (1 study, 19 children: RR 0.39,
      95% CI 0.14 to 1.06). AUTHORS' CONCLUSIONS: Data from RCTs for any intervention
      used in improve kidney outcomes in children with HSP are very sparse except for
      short-term prednisone. There was no evidence of benefit of prednisone in
      preventing serious long-term kidney disease in HSP.

PMID- 19588366
TI  - Haloperidol plus promethazine for psychosis-induced aggression.
AB  - BACKGROUND: Health services often manage agitated or violent people, and for
      emergency psychiatric services such behaviour is particularly prevalent (10%).
      The drugs used in this situation should ensure that the person swiftly and safely
      regains composure. OBJECTIVES: To examine whether haloperidol plus promethazine
      is an effective treatment for psychosis induced agitation/aggression. SEARCH
      STRATEGY: We searched the Cochrane Schizophrenia Group's Register (January 2008).
      SELECTION CRITERIA: We included all randomised clinical trials involving
      aggressive people with psychosis for which haloperidol plus promethazine was
      being used. DATA COLLECTION AND ANALYSIS: We reliably selected, quality assessed
      and extracted data from all relevant studies. For binary outcomes we calculated
      standard estimations of risk ratio (RR) and their 95% confidence intervals (CI).
      Where possible we estimated weighted number needed to treat or harm (NNT/H). MAIN
      RESULTS: We identified four relevant high quality studies. One compared the
      haloperidol plus promethazine mix with midazolam (n=301), one with lorazepam
      (n=200), one with haloperidol alone (n=316) and one with olanzapine IM (n=300).
      In Brazil, haloperidol plus promethazine was an effective means of
      tranquillisation with over two thirds of people being tranquil or sedated by 30
      minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3
      to 12). In India, compared with lorazepam, more people were tranquil or sedated
      by 30 minutes if allocated to the combination treatment (n=200, RR 0.26 CI 0.10
      to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported
      differences are negligible. One person given midazolam had respiratory depression
      (0.7%, reversed by flumazenil); one given lorazepam (1%) had respiratory
      difficulty. About 1% of people given any haloperidol treatment experienced a
      seizure. By 20 minutes intramuscular haloperidol plus promethazine was more
      tranquillising than intramuscular haloperidol (1 RCT, n=316, RR 0.65 CI 0.49 to
      0.87, NNT 7 CI 5 to 17). Haloperidol given without promethazine in this situation
      causes frequent serious adverse effects (NNH 15 CI 14 to 40). Olanzapine is as
      rapidly tranquillising as the haloperidol/promethazine combination (1 RCT, n=300,
      RR tranquil or asleep at 15 mins 0.74 CI 0.38 to 1.41), but did not have an
      enduring effect and more people needed additional drugs within four hours (1 RCT,
      n=300, RR 0.48 CI 0.33 to 0.69, NNT 5 CI 4 to 8) and to be re-assessed by the
      doctor (1 RCT, n=300, RR 0.47 CI 0.30 to 0.73, NNT 6 CI 5 to 12). AUTHORS'
      CONCLUSIONS: All treatments evaluated within the included studies are effective.
      Benzodiazepines, however, have the potential to cause respiratory depression,
      probably midazolam more so than lorazepam, and use of this group of drugs outside
      of services fully confident of observing for and managing the consequences of
      respiratory distress is difficult to justify. Haloperidol used on its own is at
      such risk of generating preventable adverse effects that unless it is the only
      choice, this evidence directs that this sole treatment should be avoided.
      Olanzapine IM is valuable when compared with haloperidol plus promethazine but
      its duration of action is short and re-injection is frequently needed.
      Haloperidol plus promethazine used in two diverse situations in Brazil and India
      has much evidence to support its swift and safe clinically valuable effects.

PMID- 19588367
TI  - Pharmacotherapy for anxiety disorders in children and adolescents.
AB  - BACKGROUND: Anxiety disorders are a potentially disabling group of disorders
      which are prevalent in childhood and adolescence. The recognition of the early
      onset of anxiety disorders, and their successful treatment with medication in
      adults, has led to the growing interest in using medication for paediatric
      anxiety disorders. OBJECTIVES: To assess the efficacy and tolerability of
      medication for treating paediatric anxiety disorders. SEARCH STRATEGY: We
      searched the Cochrane Depression, Anxiety & Neurosis Group specialised register
      (CCDANCTR-Studies), MEDLINE (via PubMed 1966 to August 2008), EMBASE (1966 to
      August 2008), and PsycINFO (1972 to August 2008). Various electronic registers
      were searched for unpublished studies. Reference lists of retrieved articles were
      searched for additional studies. SELECTION CRITERIA: All randomised controlled
      trials (RCTs) of pharmacotherapy in childhood/adolescent anxiety disorders. DATA
      COLLECTION AND ANALYSIS: Two raters independently assessed RCTs for inclusion in
      the review, collated trial data, and assessed trial quality. Investigators were
      contacted to obtain missing data. Summary statistics were stratified by
      medication class, and by medication agent for the selective serotonin reuptake
      inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a
      random effects model, heterogeneity was assessed, and subgroup/sensitivity
      analyses were undertaken. MAIN RESULTS: 22 short-term (<= 16 weeks) RCTs were
      included in the analysis (2519 participants). The majority of the trials assessed
      the efficacy of the SSRIs (N = 15).Medication and placebo response occurred in
      58.1% and 31.5% of patients, respectively (Number of studies (N) = 14, Number
      needed to treat (NNT) = 4). Medication was more effective than placebo in
      reducing overall symptom severity in OCD in a post-hoc comparison (N = 7,
      Weighted Mean Difference (WMD) = -4.45, 95%CI = -5.94, -2.97, n = 765).
      Medication was less well tolerated than placebo overall, though the absolute
      proportion of participants who withdrew due to drug-related adverse events was
      low (4.9%). AUTHORS' CONCLUSIONS: Medication treatments can be effective in
      paediatric anxiety disorders, acting to reduce core symptoms, and should be
      considered as part of the treatment of these disorders. The greatest number of
      trials showing efficacy to date have assessed the SSRIs in treating paediatric
      OCD.There is no clear evidence to show that any particular class of medication is
      more effective or better tolerated than any other. As quantitative data was only
      available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot
      be recommended, especially given concerns of dependency and treatment -related
      emergent adverse events associated with this class of drugs.Future RCTs could
      help identify potential clinical moderators of treatment efficacy. Studies of the
      long-term efficacy of medication treatment, optimal dosage, as well as direct
      comparisons of pharmacotherapy and psychotherapy are also warranted.

PMID- 19588369
TI  - Brief interventions for heavy alcohol users admitted to general hospital wards.
AB  - BACKGROUND: Brief interventions involve a time-limited intervention focusing on
      changing behaviour. They are often motivational in nature using counselling
      skills to encourage a reduction in alcohol consumption. OBJECTIVES: To determine
      whether brief interventions reduce alcohol consumption and improve outcomes for
      heavy alcohol users admitted to general hospital inpatient units. SEARCH
      STRATEGY: We searched the Cochrane Drug and Alcohol Group Register of Trials
      (June 2008) the Cochrane Central Register of Controlled Trials (The Cochrane
      Library 2, 2008), MEDLINE January 1966-June 2008, CINAHL 1982-June 2008, EMBASE
      1980-June 2008 using the search strategy developed by the Cochrane Drug and
      Alcohol Group. We hand searched relevant journals, conference proceedings and
      contacted experts in the field. SELECTION CRITERIA: All prospective randomised
      controlled trials and controlled clinical trials were eligible for inclusion.
      Participants were adults (16 years or older) admitted to general inpatient
      hospital care for any reason other than specifically for alcohol treatment and
      received brief interventions (of up to 3 sessions) compared to no or regular
      treatment. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected
      the studies and extracted data. Where appropriate random effects meta-analysis
      and sensitivity analysis were performed. MAIN RESULTS: Eleven studies involving
      2441 participants were included in this review. Three results were non
      significant and one result was significant mean alcohol consumption per week
      change scores from baseline (P0.02). AUTHORS' CONCLUSIONS: The evidence for brief
      interventions delivered to heavy alcohol users admitted to general hospital is
      still inconclusive. From data extracted from two studies it appears that alcohol
      consumption could be reduced at one year follow up though further research is
      recommended. Few studies have been retrieved and the results were difficult to
      combine because of the different measures used to assess alcohol consumption.

PMID- 19588368
TI  - WITHDRAWN: Aerobic exercise training programmes for improving physical and
      psychosocial health in adults with Down syndrome.
AB  - BACKGROUND: Although physical fitness has been suggested to improve physical and
      psychosocial health for a variety of population profiles, there is a lack of
      information about the safety and effectiveness of aerobic exercise for adults
      with Down syndrome. OBJECTIVES: To evaluate the effectiveness and safety of
      aerobic exercise training programmes for physiological and psychosocial outcomes
      in adults with Down syndrome. SEARCH STRATEGY: Search terms and synonyms for
      "aerobic exercise" and "Down syndrome" were used within the following databases:
      CENTRAL (2007, Issue 1); MEDLINE via PUBMED (1966 to March 2007); EMBASE (2005 to
      April 2007); CINAHL (1982 to March 2007); LILACS (1982 to March 2007); PsycINFO
      (1887 to March 2007); ERIC (1966 to March 2007); CCT (March 2007); Academic
      Search Elite (to March 2007), C2- SPECTR (to March 2007 ), NRR (2007 Issue 1),
      ClinicalTrials.gov (accessed March 2007) and within supplements of Medicine and
      Science in Sports and Exercise. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials using supervised aerobic exercise training
      programmes with behavioral components accepted as co-interventions. DATA
      COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed
      methodological quality and extracted data. Where appropriate, data was pooled
      using meta-analysis with a random effects model MAIN RESULTS: The two studies
      included in this trial used different kinds of aerobic activity: walking/jogging
      and rowing training. One included study was conducted in the USA, the other in
      Portugal. In the meta-analyses, only maximal treadmill grade, a work performance
      variable, was improved in the intervention group after aerobic exercise training
      programmes (-4.26 [95% CI -6.45, -2.06]) grade. The other outcomes in the meta
      analysis showed no significant differences between intervention and control
      groups, as expressed by weighted mean difference: VO(2) peak -0.30 (95% CI -377,
      3.17) mL.Kg.min(-1); peak heart rate, -2.84 (95% CI -10.73, 5.05) bpm;
      respiratory exchange ratio, 0.01 (95% CI -0.04, 0.06); pulmonary ventilation, 
      5.86 (95% CI -16.06, 4.34) L.min(-1). 30 other measures including work
      performance, oxidative stress and body composition variables could not be
      combined in the meta-analysis. Apart from work performance, trials reported no
      significant improvements in these measures. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support improvement in physical or psychosocial outcomes
      of aerobic exercise in adults with Down syndrome. Although evidence exists which
      supports improvements in physiological and psychological aspects from strategies
      using mixed physical activity programmes, well-conducted research which examines
      long-term physical outcomes, adverse effects, psychosocial outcomes and costs are
      required before informed practice decisions can be made.

PMID- 19588370
TI  - Adjuvant platinum-based chemotherapy for early stage cervical cancer.
AB  - BACKGROUND: Patients with early stage cervical cancer (stages IA2, IB1 or IIA)
      with risk factors such as lymph node metastasis, lympho vascular space invasion,
      depth invasion of more than 10mm, microscopic parametrial invasion, non-squamous
      histology and positive surgical margins have a high risk of recurrence when
      compared to patients with early stage cervical cancer with no risk factors for
      recurrence. OBJECTIVES: To evaluate the effectiveness and safety of platinum
      based adjuvant chemotherapy after radical hysterectomy, radiotherapy, or both in
      the treatment of early stage cervical cancer (stages IA2, IB1 or IIA). SEARCH
      STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register,
      The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane
      Library Issue 1, 2009), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and
      Cancerlit, the National Research Register and Clinical Trials register, with no
      language restriction. Abstracts of scientific meetings and the citation lists of
      included studies and other relevant publications were checked through hand
      searching and experts in the field were contacted to identify further reports of
      trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing
      adjuvant radiotherapy with adjuvant radiotherapy and cisplatin-chemotherapy after
      radical surgery for early stage cervix cancer were included. DATA COLLECTION AND
      ANALYSIS: Two review authors extracted data independently to assess whether the
      studies met the specified inclusion criteria. Any discrepancies were solved by a
      third and a forth review author. Meta-analysis was performed using a random
      effects model, with death and disease progression as outcomes. MAIN RESULTS:
      Three trials were included. Two trials enrolling 325 participants, of whom 297
      (91%) were assessed and compared radiotherapy and chemotherapy with radiotherapy
      alone found that adjuvant chemotherapy significantly reduced the risk of death
      (hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and
      disease progression (HR = 0.47, 95%CI: 0.30 to 0.74), with no heterogeneity
      between trials (I(2) = 0% for both meta-analyses). One trial assessing 71
      participants compared chemotherapy followed by radiotherapy with radiotherapy
      alone and found no significant difference between the two groups (HR = 1.34;
      95%CI: 0.24 to 7.66). The median follow up of patients varied from 29 to 42
      months. AUTHORS' CONCLUSIONS: The addition of platinum-based chemotherapy to
      radiotherapy may offer clinical benefit in the adjuvant treatment of early stage
      cervical cancer with risk factors for recurrence. However, the evidence is
      limited because the selected studies were quantitatively and qualitatively
      limited, with small number of patients and limited period of follow-up.

PMID- 19588371
TI  - Interventions to reduce haemorrhage during myomectomy for fibroids.
AB  - BACKGROUND: Uterine myomas (fibroids) are benign tumours of the uterus.
      Myomectomy, the surgical removal of myomas, is an important treatment option
      especially for women who wish to preserve their uteri. The major problem with
      myomectomy is excessive bleeding, which can be life-threatening and prolong
      postoperative stay. Knowledge of the effectiveness of the interventions to reduce
      bleeding during myomectomy is essential to enable evidence-based clinical
      decisions. OBJECTIVES: To assess the effectiveness, safety, tolerability, and
      costs of interventions to reduce blood loss during myomectomy. SEARCH STRATEGY:
      Electronic searches were undertaken in the Cochrane Menstrual Disorders and
      Subfertility Group Specialised Register, CENTRAL (The Cochrane Library 2008,
      Issue 3), MEDLINE (1950 to September 2008), EMBASE (1980 to September 2008),
      CINAHL (1982 to September 2008), and PsycINFO (up to September 2008). SELECTION
      CRITERIA: Only randomised controlled trials (RCTs) that compared the use of
      interventions to reduce blood loss during myomectomy to placebo or no treatment
      were included. DATA COLLECTION AND ANALYSIS: The two authors independently
      selected RCTs for inclusion, assessed the methodological quality of trials, and
      extracted data. We expressed study results as mean differences (MD) for
      continuous data and odds ratios for dichotomous data, with 95% confidence
      intervals (CI). MAIN RESULTS: Ten RCTs with 531 participants met our inclusion
      criteria: intramyometrial vasopressin and analogues (two trials), intravenous
      oxytocin (two trials), and one RCT for each of the interventions vaginal
      misoprostol, peri-cervical tourniquet, chemical dissection with sodium-2
      mercaptoethane sulfonate (mesna), intramyometrial bupivacaine plus epinephrine,
      tranexamic acid and the enucleation of myoma by morcellation while it is attached
      to the uterus. We found significant reductions in blood loss with misoprostol (MD
      -149.00 ml, 95% CI -229.24 to -68.76), vasopressin and analogues (MD -298.72 ml,
      95% CI -593.10 to -4.34), bupivacaine plus epinephrine (MD -68.60 ml, 95% CI 
      93.69 to - 43.51), tranexamic acid (MD -243 ml, 95% CI -460 to -25.98), and peri
      cervical tourniquet (MD -1870.00 ml, 95% CI -2547.16 to -1192.84). There was no
      evidence of effect on blood loss with myoma enucleation by morcellation or
      oxytocin. The trials did not assess the tolerability and costs of the different
      interventions. AUTHORS' CONCLUSIONS: Evidence is limited from a few RCTs that
      misoprostol, vasopressin, bupivacaine plus epinephrine, tranexamic acid,
      tourniquet, and mesna may reduce bleeding during myomectomy. There is no evidence
      that oxytocin and morcellation have an effect on intraoperative blood loss. There
      is a need for adequately powered RCTs to shed more light on the effectiveness,
      safety, and costs of different interventions in reducing blood loss during
      myomectomy.

PMID- 19588372
TI  - Anti-angiogenic therapies for metastatic colorectal cancer.
AB  - BACKGROUND: Angiogenesis inhibitors have been developed to block tumour
      angiogenesis and target vascular endothelial cells. While some of them have
      already been approved by the health authorities and are successfully integrated
      into patient care, many others are still under development, and the clinical
      value of this approach has to be established. OBJECTIVES: To assess the efficacy
      and toxicity of targeted anti-angiogenic therapies, in addition to chemotherapy,
      in patients with metastatic colorectal cancer. Primary endpoints are both
      progression-free and overall survival. Response rates, toxicity and secondary
      resectability were secondary endpoints. Comparisons were first-line chemotherapy
      in combination with angiogenesis inhibitor, to the same chemotherapy without
      angiogenesis inhibitor; and second-line chemotherapy, to the same chemotherapy
      without angiogenesis inhibitor. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials, MEDLINE, as well as proceedings from ECCO, ESMO
      and ASCO until November 2008. In addition, reference lists from trials were
      scanned, experts in the field and drug manufacturers were contacted to obtain
      further information. SELECTION CRITERIA: Randomized controlled trials on targeted
      anti-angiogenic drugs in metastatic colorectal cancer (MCRC). DATA COLLECTION AND
      ANALYSIS: Data collection and analysis was performed, according to a previously
      published protocol. Because individual patient data was not provided, aggregate
      data had to be used for the analysis. Summary statistics for the primary
      endpoints were hazard ratios (HR's) and their 95% confidence intervals. MAIN
      RESULTS: At present, eligible first line trials for this meta-analysis were
      available for bevacizumab (5 trials including 3101 patients) and vatalanib (1
      trial which included 1168 patients). The overall HR s for PFS (0.61, 95% CI 0.45 
      0.83) and OS (0.81, 95% 0.73 - 0.90) for the comparison of first-line
      chemotherapy, with or without bevacizumab, confirms significant benefits in
      favour of the patients treated with bevacizumab. However, the effect on PFS shows
      significant heterogeneity. For second-line chemotherapy, with or without
      bevacizumab, a benefit in both PFS (HR 0.61, 95% CI 0.51 - 0.73) and OS (HR 0.75,
      95% CI 0.63-0.89) was demonstrated in a single, randomized trial. While
      differences in treatment-related deaths and 60-day mortality were not
      significant, higher incidences in grade III/IV hypertension, arterial
      thrombembolic events and gastrointestinal perforations were observed in the
      patients treated with bevacizumab. For valatanib, currently available data showed
      a non-significant benefit in PFS and OS. AUTHORS' CONCLUSIONS: The addition of
      bevacizumab to chemotherapy of metastatic colorectal cancer prolongs both PFS and
      OS in first-and second-line therapy.

PMID- 19588373
TI  - Interventions for previously untreated patients with AIDS-associated non
      Hodgkin's lymphoma.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is known to be
      associated with an increased risk of non-Hodgkin's lymphoma (NHL). The majority
      of lymphomas (>80%) occurring during immunosuppression are aggressive B-cell in
      origin and have a high-to-intermediate histology grade. Treatment of NHL is not
      standardized. OBJECTIVES: To assess the clinical effectiveness and safety of
      single agent or combination chemotherapy with or without immunochemotherapy
      (rituximab) and with or without highly active antiretroviral therapy (HAART) on
      overall survival (OS) and disease-free survival (DFS) for previously untreated
      patients with AIDS-related NHL. SEARCH STRATEGY: The Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (1966-March 6,
      2009), EMBASE (1988-March 6, 2009), LlLACS (1982 to February 17, 2009), Gateway
      (March 6, 2009), and AIDSearch (2006 -February 2008) were used to identify
      published, potentially eligible trials. Further, we searched several electronic
      sources. For additional information see the Cochrane HIV/AIDS Group search
      strategy. SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing the
      effectiveness of systemic treatments for previously untreated AIDS-related NHL.
      There were no age or language restrictions. DATA COLLECTION AND ANALYSIS: Authors
      independently assessed relevant studies for inclusion; four RCTs were selected.
      No meta-analysis was attempted due to clinical heterogeneity. MAIN RESULTS: Four
      RCTs that included 857 patients (number range: 30 to 485) met the inclusion
      criteria. The studies have a high risk of bias; three RCTs were conducted in the
      United States and one was a multi-national, multi-centre RCT performed in France
      and Italy. One of the trials included only men. It was impossible to pool data
      for any of the outcomes due to the differences in the interventions assessed in
      these RCTs. Overall survival did not differ significantly between treatment
      groups. Disease free survival (DFS) was reported in two of the four RCTs, but it
      was not statistically significant between treatment groups. AUTHORS' CONCLUSIONS:
      We found no evidence that the systemic interventions for untreated patients with
      AIDS-related NHL provide superior clinical effectiveness for improving OS, DSF,
      and tumour response rate; however, this conclusion is based on four RCTs with
      limited sample size and variable quality. More adequately powered RCTs that have
      low risk of bias are necessary to determine the real benefit or harm of
      interventions to treat this population. Overall survival (OS), DFS, and quality
      of life should be included as endpoints.

PMID- 19588375
TI  - Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB
      vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B
      and Haemophilus influenzae B (HIB).
AB  - BACKGROUND: Advantages to combining childhood vaccines include reducing the
      number of visits, injections and patient discomfort, increasing compliance, and
      optimizing prevention. The World Health Organization recommends that routine
      infant immunization programs include a vaccination against Haemophilus influenza
      type B (HIB) in the combined diphtheria, tetanus, pertussis (DTP)-hepatitis B
      (HBV) vaccination. The effectiveness and safety of the combined vaccine should be
      carefully and systematically assessed to ensure their acceptability by the
      community. OBJECTIVES: To compare the effectiveness of combined DTP-HBV-HIB
      vaccine with DTP-HBV and HIB vaccinations. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2009, issue 1) which contains the Acute Respiratory Infection Group's Specialized
      Register; MEDLINE (January 1966 to March 2009) and EMBASE (January 1990 to March
      2009). SELECTION CRITERIA: Randomized or quasi-randomized controlled trials
      comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without
      three types of inactivated poliovirus (IPV) or concomitant oral polio vaccine
      (OPV) in any dose, preparation or time schedule, compared with separate vaccines
      or placebo, administered to infants aged up to two years. DATA COLLECTION AND
      ANALYSIS: Two review authors independently inspected references identified by the
      searches and evaluated them against the inclusion criteria, extracted data and
      assessed the methodological quality of included trials. MAIN RESULTS: Meta
      analysis was performed to pool the results of 18 studies. There were no data on
      clinical outcomes for the primary outcome and all studies used immunogenicity and
      reactogenicity (adverse events). In two immunological responses the combined
      vaccine achieved lower responses than the separate vaccines for HIB and HBV.
      Comparison found little heterogeneity. No significant differences in
      immunogenicity were found for pertussis, diphtheria, polio and tetanus. Serious
      adverse events were comparable. Minor adverse events were more common in children
      given the combined vaccine. AUTHORS' CONCLUSIONS: We could not conclude that the
      immune responses elicited by the combined vaccine were different from, or
      equivalent to, the separate vaccines. Data for the primary outcome (prevention of
      disease) were lacking. There was significantly less immunological response for
      HIB and HBV, and more local reactions in the combined injections. However, these
      differences rely mostly on one study each. Studies did not use an intention-to
      treat analysis and we were uncertain about the risk of bias in many of the
      studies. These results are therefore inconclusive. Studies addressing clinical
      end-points whenever possible, using correct methodology and a large enough sample
      size should be conducted.

PMID- 19588374
TI  - A combination drug of abacavir-lamivudine-zidovudine (Trizivir) for treating HIV
      infection and AIDS.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) has become one of the greatest
      challenges to global public health. In 2007 UNAIDS estimated that 33.2 million
      people were living with HIV. Currently recommended regimens for initiating HIV
      treatment consist of either a non-nucleoside reverse transcriptase inhibitor
      (NNRTI) or ritonvair-boosted protease inhibitor (PI) combined with two nucleoside
      reverse transcriptase inhibitors (NRTIs); however, there may be some patients for
      whom NNRTIs and PIs may not be appropriate. OBJECTIVES: The aim of this review
      was to evaluate the effects of Trizivir, a fixed-dose combination of three NRTIs
      (abacavir-lamivudine-zidovudine) for initial treatment of HIV infection. SEARCH
      STRATEGY: In February 2008, we searched the Cochrane Library, PubMed, EMBASE,
      AIDSearch and GATEWAY and checked reference lists of identified articles. In May
      2009, we repeated the search in PubMed and the Cochrane Library. SELECTION
      CRITERIA: We selected randomized controlled trials (RCTs) with a minimum follow
      up time of six months which compared Trizivir with either a PI- or NNRTI-based
      therapy among antiretroviral-naive HIV-infected patients aged at least 13 years.
      DATA COLLECTION AND ANALYSIS: Three authors independently extracted data. We
      calculated the relative risk (RR) or mean difference (as appropriate) for each
      outcome with its 95% confidence interval (CI) and conducted meta-analysis using
      the random-effects method because of significant statistical heterogeneity
      (P<0.1). MAIN RESULTS: We identified nine potentially eligible RCTs, three of
      which met our inclusion criteria. One trial compared Trizivir to efavirenz (an
      NNRTI) plus two or three NRTIs; the second trial compared Trizivir to a treatment
      based on the PI nelfinavir; and the third compared Trizivir to atazanavir (a PI)
      plus two NRTIs. Overall, there was no significant difference in the incidence of
      virological failure between participants on Trizivir and those on PI-based or
      NNRTI-based therapy (three trials, N=1687; RR 1.14, 95% CI 0.56 to 2.32).
      However, there was significant heterogeneity between the results of the three
      trials (heterogeneity P=0.009, I(2)=79%), with a significant increase in
      virological failure for Trizivir compared to efavirenz (N=1147; RR 1.93, 95% CI
      1.46 to 2.55) but no difference between Trizivir and PIs (two trials, N=540; RR
      0.82, 95% CI 0.50 to 1.36). We found no significant differences between Trizivir
      and either the PI or NNRTI on CD4+ cell counts (standardized mean difference 
      0.01, 95% CI -0.11 to 0.09, heterogeneity P=0.59, I(2)=0%), severe adverse events
      (RR 1.41, 95% CI 0.61 to 3.25, heterogeneity P=0.03, I(2)=73%) and
      hypersensitivity reactions (RR 4.04, 95% CI 0.41 to 40.02, heterogeneity P=0.03,
      I(2)=72%). Only the studies involving PIs reported the effect of the treatment
      regimens on the lipid profile. One study found that at 96 weeks, the mean
      increase in total cholesterol from baseline was significantly lower with Trizivir
      than with nelfinavir, but there were no significant differences with triglyceride
      levels. The second study found the fasting lipid profile to be comparable in both
      the Trizivir and atazanavir arms at 48 weeks. AUTHORS' CONCLUSIONS: Our findings
      indicate that Trizivir remains a viable option for initiating antiretroviral
      therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia
      and those who do not tolerate ritonavir.

PMID- 19588376
TI  - Corticosteroid injection for de Quervain's tenosynovitis.
AB  - BACKGROUND: De Quervain's tenosynovitis is a disorder characterised by pain on
      the radial (thumb) side of the wrist and functional disability of the hand. It
      can be treated by corticosteroid injection, splinting and surgery. OBJECTIVES: To
      summarise evidence on the efficacy and safety of corticosteroid injections for de
      Quervain's tenosynovitis. SEARCH STRATEGY: We searched the following databases:
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2009, Issue 2), MEDLINE (1966 to April 2009), EMBASE (1956 to April
      2009), CINAHL (1982 to April 2009), AMED (1985 to April 2009), DARE, Dissertation
      Abstracts and PEDro (physiotherapy evidence database). SELECTION CRITERIA:
      Randomised and controlled clinical trials evaluating the efficacy and safety of
      corticosteroid injections for de Quervain's tenosynovitis. DATA COLLECTION AND
      ANALYSIS: After screening abstracts of studies identified by the search we
      obtained full text articles of studies which fulfilled the selection criteria. We
      extracted data using a predefined electronic form. We assessed the methodological
      quality of included trials by using the checklist developed by Jadad and the
      Delphi list. We extracted data on the primary outcome measures: treatment
      success; severity of pain or tenderness at the radial styloid; functional
      impairment of the wrist or hand; and outcome of Finkelstein's test, and the
      secondary outcome measures: proportion of patients with side effects; type of
      side effects and patient satisfaction with injection treatment. MAIN RESULTS: We
      found one controlled clinical trial of 18 participants (all pregnant or lactating
      women) that compared one steroid injection with methylprednisolone and
      bupivacaine to splinting with a thumb spica. All patients in the steroid
      injection group (9/9) achieved complete relief of pain whereas none of the
      patients in the thumb spica group (0/9) had complete relief of pain, one to six
      days after intervention (number needed to treat to benefit (NNTB) = 1, 95%
      confidence interval (CI) 0.8 to 1.2). No side effects or local complications of
      steroid injection were noted. AUTHORS' CONCLUSIONS: The efficacy of
      corticosteroid injections for de Quervain's tenosynovitis has been studied in
      only one small controlled clinical trial, which found steroid injections to be
      superior to thumb spica splinting. However, the applicability of our findings to
      daily clinical practice is limited, as they are based on only one trial with a
      small number of included participants, the methodological quality was poor and
      only pregnant and lactating women participated in the study. No adverse effects
      were observed.

PMID- 19588377
TI  - Magnification devices for endodontic therapy.
AB  - BACKGROUND: After the introduction of microsurgical principles in endodontics,
      involving new techniques for root canal treatment, there has been a continuous
      search for enhancing the visualisation of the surgical field. It would be
      interesting to know if the technical advantages for the operator brought in by
      magnification devices like surgical microscope, endoscope and magnifying loupes,
      are also associated with advantages for the patient, in terms of improvement of
      clinical and radiographic outcomes. OBJECTIVES: The purpose of this systematic
      review was to evaluate and compare the effects of endodontic treatment performed
      with the aid of magnification devices versus endodontic treatment without
      magnification devices. We also aimed at comparing among them the different
      magnification devices used in endodontics (microscope, endoscope, magnifying
      loupes). SEARCH STRATEGY: The Cochrane Oral Health Group Trials Register,
      CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies.
      Handsearching included nine dental journals. The bibliographies of relevant
      clinical trials and relevant articles were checked for identifying studies
      outside the handsearched journals. Seven manufacturers of instruments in the
      field of endodontics and/or endodontic surgery, as well as the authors of the
      identified randomised controlled trials (RCTs) were contacted in order to
      identify unpublished or ongoing RCTs. There were no language restrictions. The
      last electronic search was conducted on 2nd April 2009, and the last
      handsearching was undertaken on 31st January 2009. SELECTION CRITERIA: All
      randomised and quasi-randomised trials comparing endodontic therapy performed
      with or without using one or more types of magnification device, as well as
      randomised and quasi-randomised trials comparing two or more magnification
      devices used as an adjunct to endodontic therapy were considered. DATA COLLECTION
      AND ANALYSIS: Screening of studies and data extraction were conducted
      independently and in duplicate. The Cochrane Collaboration statistical guidelines
      were to be followed for data synthesis. MAIN RESULTS: No trial could be included
      in the present review. All of the prospective trials that were identified, all
      dealing with endodontic surgery, had to be excluded for various reasons. Only one
      RCT was identified comparing three magnificators (magnifying loupes, surgical
      microscope, endoscope) in endodontic surgery. No RCT was found that compared the
      outcome of endodontic therapy using or without using a given magnification
      device. AUTHORS' CONCLUSIONS: No objective conclusion can be drawn from the
      results of this review as no article was identified in the current literature
      that satisfied the criteria for inclusion. It is unknown if and how the type of
      magnification device affects the treatment outcome, considering the high number
      of factors that may have a significant impact on the success of endodontic
      surgical procedure. This should be investigated by further long-term RCTs with
      large sample size. Technical advantages of magnificators have been widely
      reported in low evidence level studies, but they should be systematically
      addressed to know if there can be the clinical indication for using a given
      magnification device for specific clinical situations, such as for molar teeth,
      or if they can all be used interchangeably. Well-designed RCTs should also be
      performed to determine the true difference in terms of treatment success rates
      between using or not using a magnification device in both conventional and
      surgical endodontic treatment, if any exist.

PMID- 19588378
TI  - Family support for reducing morbidity and mortality in people with HIV/AIDS.
AB  - BACKGROUND: Care and support play a critical role in assisting people who are HIV
      positive to understand the need for prevention and to enable them to protect
      others. As the HIV/AIDS pandemic progresses and HIV-seropositive individuals
      contend with devastating illness, it seemed timely to inquire if they receive
      support from family members. It also was important to develop a normative idea of
      how much family support exists and from whom it emanates. OBJECTIVES: To assess
      the effect of family support on morbidity, mortality, quality of life, and
      economics in families with at least one HIV-infected member, in developing
      countries. SEARCH STRATEGY: The following databases were searched:The Cochrane
      Central Register for Controlled Trials (CENTRAL), the Cochrane Database of
      Systematic Reviews, MEDLINE, AIDSLINE, CINAHL, Dissertation Abstracts
      International (DAI), EMBASE, BIOSIS, SCISEARCH, the Cochrane HIV/AIDS group
      specialized register, INDMED, Proquest, and various South Asian abstracting
      databases, will be included in the database list. The publication sites of the
      World Health Organization, the US Centers for Disease Control and Prevention, and
      other international research and non-governmental organizations. An extensive
      search strategy string was developed in consultation with the trial search
      coordinator of the HIV/AIDS Review Group. Numerous relevant keywords were
      included in the string to get an exhaustive electronic literature search. The
      search was not restricted by language. Articles from other languages were
      translated into English with the help of experts. A hand search was carried out
      in many journals and abstracts of the conference proceedings of national and
      international conferences related to AIDS (e.g. the International Conference on
      HIV/AIDS and STI in Africa [ICASA]). Efforts also were made to contact experts to
      identify unpublished research and trials still underway. SELECTION CRITERIA:
      Intervention studies. Randomized control trials (RCTs) and quasi-RCTs involving
      HIV-infected individuals with family support in developing countries. DATA
      COLLECTION AND ANALYSIS: We independently screened the results of the search to
      select potentially relevant studies and to retrieve the full articles. We
      independently applied the inclusion criteria to the potentially relevant studies.
      No studies were identified that fulfilled the selection criteria. MAIN RESULTS:
      We were unable to find any trials of family support in reducing the morbidity and
      mortality in HIV-infected persons in developing countries. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to bring out the effect of family support in
      reducing the morbidity and mortality of HIV-infected persons in developing
      countries. This review has highlighted the dearth of high-quality quantitative
      research about family support. There is a clear need for rigorous studies of the
      clinical effects of family support on people with HIV in developing countries.

PMID- 19588379
TI  - The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant
      women.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a very common cause of vaginitis that has
      been associated with a high incidence of obstetric and gynaecologic complications
      and increased risk of HIV-1 transmission. This has led to renewed research
      interest in its treatment. OBJECTIVES: To assess the effects of antimicrobial
      agents on BV in non-pregnant women. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE,
      EMBASE, LILACS, and African Healthline (December 2007); and proceedings of
      relevant international conferences (from 1981 to date). SELECTION CRITERIA:
      Randomised controlled trials comparing any two or more antimicrobial agents, or
      antimicrobial agents with placebo or no treatment, in women with clinical or Gram
      stain criteria of BV. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data from the original publications while
      the third author cross checked the data. MAIN RESULTS: Twenty-four trials
      involving 4422 participants were reviewed. Most examined symptomatic women only.
      Only seven trials analysed results by intention to treat; we re-analysed the
      remainder.Compared with placebo, clindamycin showed a lower rate of treatment
      failure (relative risk (RR) 0.25, 95% confidence interval (CI) 0.16 to 0.37).
      Clindamycin and metronidazole showed identical rates of treatment failure,
      irrespective of regimen type, at two and four-week follow up (RR 1.01, 95% CI
      0.69 to 1.46; RR 0.91, 95% CI 0.70 to 1.18, respectively). Clindamycin tended to
      cause a lower rate of adverse events (RR 0.75, 95% CI 0.56 to 1.02); metallic
      taste, and nausea and vomiting were more common in the metronidazole group (RR
      0.08, 95% CI 0.1 to 0.59; RR 0.23, 95% CI 0.10 to 0.51, respectively). Given
      intravaginally as gelatin tablets, lactobacillus was more effective than oral
      metronidazole (RR 0.20, 95% CI 0.05 to 0.08). Similarly, oral lactobacillus
      combined with metronidazole was more effective than metronidazole alone (RR 0.33,
      95% CI 0.14 to 0.77). Clindamycin showed a lower rate of clinical failure than
      triple sulfonamide cream (RR 0.46, 95% CI 0.29 to 0.72). Hydrogen peroxide douche
      showed a higher rate of clinical failure (RR 1.75, 95% CI 1.02 to 3.00) and
      adverse events (RR 2.33, 95% CI 1.21 to 4.52) than a single 2 g dose of
      metronidazole. AUTHORS' CONCLUSIONS: Clindamycin preparations, oral
      metronidazole, and oral and intravaginal tablets of lactobacillus were effective
      for bacterial vaginosis. Hydrogen peroxide douche and triple sulphonamide cream
      were ineffective. Metronidazole caused metallic taste, nausea and vomiting. We
      need better-designed trials with larger sample sizes to test the effectiveness of
      promising drugs.

PMID- 19588380
TI  - Incentive spirometry for prevention of postoperative pulmonary complications in
      upper abdominal surgery.
AB  - BACKGROUND: Upper abdominal surgical procedures are associated with a high risk
      of postoperative pulmonary complications. The risk and severity of postoperative
      pulmonary complications can be reduced by the judicious use of therapeutic
      manoeuvres that increase lung volume. Our objective was to assess the effect of
      incentive spirometry (IS) compared to no therapy, or physiotherapy including
      coughing and deep breathing, on all-cause postoperative pulmonary complications
      and mortality in adult patients admitted for upper abdominal surgery. OBJECTIVES:
      To assess the effects of incentive spirometry compared to no such therapy (or
      other therapy) on all-cause postoperative pulmonary complications (atelectasis,
      acute respiratory inadequacy) and mortality in adult patients admitted for upper
      abdominal surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 3), MEDLINE,
      EMBASE, and LILACS (from inception to July 2006). There were no language
      restrictions. SELECTION CRITERIA: We included randomized controlled trials of
      incentive spirometry in adult patients admitted for any type of upper abdominal
      surgery, including patients undergoing laparoscopic procedures. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed trial quality and extracted
      data. MAIN RESULTS: We included 11 studies with a total of 1754 participants.
      Many trials were of only moderate methodological quality and did not report on
      compliance with the prescribed therapy. Data from only 1160 patients could be
      included in the meta-analysis. Three trials (120 patients) compared the effects
      of incentive spirometry with no respiratory treatment. Two trials (194 patients)
      compared incentive spirometry with deep breathing exercises. Two trials (946
      patients) compared incentive spirometry with other chest physiotherapy. All
      showed no evidence of a statistically significant effect of incentive spirometry.
      There was no evidence that incentive spirometry is effective in the prevention of
      pulmonary complications. AUTHORS' CONCLUSIONS: We found no evidence regarding the
      effectiveness of the use of incentive spirometry for prevention of postoperative
      pulmonary complications in upper abdominal surgery. This review underlines the
      urgent need to conduct well-designed trials in this field. There is a case for
      large randomized trials of high methodological rigour in order to define any
      benefit from the use of incentive spirometry regarding mortality.

PMID- 19588381
TI  - Overground physical therapy gait training for chronic stroke patients with
      mobility deficits.
AB  - BACKGROUND: Overground gait training forms a major part of physical therapy
      services for chronic stroke patients in almost every setting. Overground gait
      training refers to physical therapists' observation and cueing of the patient's
      walking pattern along with related exercises, but does not include high
      technology aids such as functional electrical stimulation or body weight support.
      OBJECTIVES: To assess the effects of overground physical therapy gait training on
      walking ability for chronic stroke patients with mobility deficits. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched
      March 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 2, 2008), MEDLINE (1966 to May 2008), EMBASE (1980 to May
      2008), CINAHL (1982 to May 2008), AMED (1985 to March 2008), Science Citation
      Index Expanded (1981 to May 2008), ISI Proceedings (Web of Science, 1982 to May
      2006), Physiotherapy Evidence Database (http://www.pedro.org.au/) (May 2008),
      REHABDATA (http://www.naric.com/research/rehab/) (1956 to May 2008),
      http://www.clinicaltrials.gov (May 2008), http://www.controlled-trials.com/ (May
      2008), and http://www.strokecenter.org/ (May 2008). We also searched reference
      lists of relevant articles, and contacted authors and trial investigators.
      SELECTION CRITERIA: Randomised controlled trials comparing overground physical
      therapy gait training with a placebo intervention or no treatment for chronic
      stroke patients with mobility deficits. DATA COLLECTION AND ANALYSIS: Pairs of
      authors independently selected trials. Three authors independently extracted data
      and assessed quality. We contacted study authors for additional information. MAIN
      RESULTS: We included nine studies involving 499 participants. We found no
      evidence for a benefit on the primary variable, post-test gait function, based on
      three studies with 269 participants. Uni-dimensional performance variables did
      show significant effects post-test. Gait speed increased by 0.07 metres per
      second (95% confidence interval (CI) 0.05 to 0.10) based on seven studies with
      396 participants, timed up-and-go (TUG) test improved by 1.81 seconds (95% CI 
      2.29 to -1.33), and six-minute-walk test (6MWT) increased by 26.06 metres (95% CI
      7.14 to 44.97) based on four studies with 181 participants. We found no
      significant differences in deaths/disabilities or in adverse effects, based on
      published reports or personal communication from all of the included studies.
      AUTHORS' CONCLUSIONS: We found insufficient evidence to determine if overground
      physical therapy gait training benefits gait function in patients with chronic
      stroke, though limited evidence suggests small benefits for uni-dimensional
      variables such as gait speed or 6MWT. These findings must be replicated by large,
      high quality studies using varied outcome measures.

PMID- 19588382
TI  - Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head
      and neck cancer.
AB  - BACKGROUND: Tumour hypoxia increases tumour invasiveness and has a negative
      impact on response to therapy. Hypoxic tumours are also associated with severely
      anaemic individuals. It has therefore been hypothesised that correcting anaemia,
      by increasing haemoglobin levels using erythropoietin, improves tumour
      oxygenation and consequently the patient's prognosis. OBJECTIVES: To assess
      whether combined treatment with radiotherapy and erythropoietin (RT plus EPO) is
      better than standard radiotherapy (RT alone) for the treatment of head and neck
      cancer patients. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat
      Disorders Group Trials Register; the Cochrane Central Register of Controlled
      Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews;
      Cambridge Scientific Abstracts; mRCT and additional sources for published and
      unpublished trials. The date of the most recent search was 24 February 2009.
      SELECTION CRITERIA: Two independent authors assessed identified studies according
      to the eligibility criteria: RCTs which delivered radiotherapy combined with or
      without erythropoietin, in patients of any age with head and neck cancer of any
      stage or type. In addition, trials administering concomitant iron therapy among
      one or both arms were also eligible. DATA COLLECTION AND ANALYSIS: For
      statistical analysis of survival data, we computed a weighted estimate of the
      typical treatment effect across studies. We used Chi(2) heterogeneity tests to
      test for statistical heterogeneity among trials and performed the statistical
      analyses using Review Manager 5.0. MAIN RESULTS: Five RCTs with a total of 1397
      patients were included. Pooled data yielded a significantly worse overall
      survival (OS) for RT plus EPO as compared to RT alone (Peto odds ratio 0.73; 95%
      confidence interval (CI) 0.58 to 0.91; P = 0.005, five trials). For local
      regional tumour control (LRTC) analyses resulted in a small but non-significant
      difference between the RT alone group and the RT plus EPO group (RR 0.92; 95% CI
      0.81 to 1.03; P = 0.15, four trials). In addition, the local regional progression
      free survival (LRPFS) measured in four studies was significantly different
      between groups (Peto odds ratio 0.63; 95% CI 0.49 to 0.80; P = 0.0002, four
      trials), in favour of the RT alone group. Two studies used supplemental iron in
      the RT plus EPO group and not in the RT alone group. When excluding these studies
      from the analyses, the statistically (non-) significant differences in OS, LRTC
      and LRPFS are maintained. AUTHORS' CONCLUSIONS: There are strong suggestions that
      RT plus EPO has a negative influence on outcome as opposed to RT alone. However,
      the target haemoglobin concentration, which was higher than recommended in four
      of the five included RCTs, may have had a significant role. Nevertheless, based
      on these findings EPO should not be administered as an addition to RT outside the
      experimental setting for patients with head and neck cancer.

PMID- 19588383
TI  - Garlic for the common cold.
AB  - BACKGROUND: Garlic is alleged to have antimicrobial and antiviral properties that
      relieve the common cold, among other beneficial effects. There is widespread
      usage of garlic supplements. The common cold is associated with significant
      morbidity and economic consequences. On average, children have six to eight colds
      per year, and adults have two to four. OBJECTIVES: To determine whether garlic
      (allium sativum) is effective for either the prevention or treatment of the
      common cold, when compared to placebo, no treatment or other treatments. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2009, issue 1), which includes the Acute
      Respiratory Infections Group Specialised Register; OLDMEDLINE (1950 to 1965);
      MEDLINE (January 1966 to March Week 3, 2009); EMBASE (1974 to March 2009); and
      AMED (1985 to March 2009). SELECTION CRITERIA: Randomised controlled trials of
      common cold prevention and treatment comparing garlic with placebo, no treatment
      or standard treatment. DATA COLLECTION AND ANALYSIS: Two review authors
      independently reviewed and selected trials from searches, assessed and rated
      study quality, and extracted relevant data. MAIN RESULTS: Of the five trials
      identified as potentially relevant from our searches, only one trial met the
      inclusion criteria. This trial randomly assigned 146 volunteer participants to
      either a garlic supplement (with 180 mg of allicin content) or a placebo (once
      daily) for 12 weeks. The trial reported 65 occurrences of the common cold in the
      placebo group compared with 24 in the garlic intervention group (P < 0.001). The
      number of days of illness was lower in the garlic group compared with the placebo
      group (111 versus 366). The number of days to recovery was similar in both groups
      (4.63 versus 5.63). Because only one trial met the inclusion criteria, limited
      conclusions can be drawn. The trial relied on self-reported episodes of the
      common cold, but was of reasonable quality in terms of randomisation and
      allocation concealment. Adverse effects included rash and odour. AUTHORS'
      CONCLUSIONS: There is insufficient clinical trial evidence regarding the effects
      of garlic in preventing or treating the common cold. A single trial suggested
      that garlic may prevent occurrences of the common cold, but more studies are
      needed to validate this finding. Claims of effectiveness appear to rely largely
      on poor quality evidence.

PMID- 19588384
TI  - Concomitant hyperthermia and radiation therapy for treating locally advanced
      rectal cancer.
AB  - BACKGROUND: Surgery has been the treatment of choice for patients with rectal
      cancer. For locally advanced cancer results were poor, with high rates of
      locoregional recurrences and poor overall survival data. Adding
      (chemo)radiotherapy upfront improved results mainly in locoregional control.
      Adding hyperthermia to radiotherapy preoperatively might have an equivalent
      beneficial effect. OBJECTIVES: To quantify the potential beneficial effect of
      thermo radiation compared to chemo-radiation with respect to pathological
      complete responses, overall survival and toxicity in rectal cancer therapy.
      SEARCH STRATEGY: We identified the relevant phase II and III randomised
      controlled trials in any language trough electronic searches May 2007 of the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      Issue 1, 2007), the Cochrane Colorectal Cancer Groups Specialised Register,
      MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982). Furthermore, various
      trial databases were searched for the identification of recent completed and
      ongoing trials (metaRegister of Controlled Trials, Cancer Research UK,
      Cancer.gov, The Eastern Cooperative Oncology Group Trials Database). All studies
      identified until May 2007 were considered for inclusion in the present study.
      SELECTION CRITERIA: Only phase II and III randomised controlled clinical trials
      were included in the analysis. DATA COLLECTION AND ANALYSIS: All identified
      studies were assessed by two independent reviewers. A weighted estimate of the
      treatment effect was computed for 2, 3, 4 and 5-year survival, for local tumour
      recurrence, severe acute and late toxicity and complete tumour response (CR). CR
      was defined either clinically by disappearance of all pretreatment signs of local
      tumour or pathologically by microscopically free margins. The risk ratio (RR) and
      hazard ratio (HR) were used. Analyses were performed with the Reference Manager
      (RevMan). MAIN RESULTS: Six RCTs published between 1990 and 2007 were identified.
      A total number of 520 patients was treated, 258 in the radiotherapy only arm (RT)
      and 262 in the radiotherapy-hyperthermia arm (RHT). Four studies (424 patients)
      reported overall survival (OS) rates. After 2 years, OS was significantly better
      in the RHT group (HR 2.06; 95% CI 1.33-3.17; p=.001), but this difference
      disappeared after a longer period (3, 4 and 5 year OS). All but one studies
      reported CR rates. A significant higher CR rate was observed in the RHT group (RR
      2.81; 95% CI 1.22-6.45; p=.01). Only 2 studies reported on acute toxicity. In
      these 2 studies no significant differences were observed between the RT and the
      RHT group. Late toxicity data were not reported. AUTHORS' CONCLUSIONS: Further
      studies are needed to compare chemoradiation versus thermoradiation versus
      chemoradiation plus hyperthermia in well selected/conducted and quality
      controlled randomised trials.

PMID- 19588385
TI  - Clozapine combined with different antipsychotic drugs for treatment resistant
      schizophrenia.
AB  - BACKGROUND: Although clozapine has been shown to be the treatment of choice in
      people with schizophrenia that are resistant to treatment, one third to two
      thirds of people still have persistent positive symptoms despite clozapine
      monotherapy of adequate dosage and duration. The need to provide effective
      therapeutic interventions to patients who do not have an optimal response to
      clozapine is the most common reason for simultaneously prescribing a second
      antipsychotic drug in combination with clozapine. OBJECTIVES: To determine the
      efficacy and tolerability of various clozapine combination strategies with
      antipsychotics in people with treatment resistant schizophrenia. SEARCH STRATEGY:
      We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and
      MEDLINE (up to November 2008). We checked reference lists of all identified
      randomised controlled trials and requested pharmaceutical companies marketing
      investigational products to provide relevant published and unpublished data.
      SELECTION CRITERIA: We included only randomised controlled trials recruiting
      people of both sexes, aged 18 years or more, with a diagnosis of treatment
      resistant schizophrenia (or related disorders) and comparing clozapine plus
      another antipsychotic drug with clozapine plus a different antipsychotic drug.
      DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      resolved disagreement by discussion with third member of the team. When
      insufficient data were provided, we contacted the study authors. MAIN RESULTS:
      Three small (range of number of participants 28 to 60) randomised controlled
      trials were included in the review. Even though results from individual studies
      did not find that one combination strategy is better than the others, the
      methodological quality of included studies was too low to allow authors to use
      the collected data to answer the research question correctly. AUTHORS'
      CONCLUSIONS: In this review we considered the risk of bias too high because of
      the poor quality of the retrieved information (small sample size, heterogeneity
      of comparisons, flaws in the design, conduct and analysis). Although clinical
      guidelines recommend a second antipsychotic in addition to clozapine in partially
      responsive patients with schizophrenia, the present systematic review was not
      able to show if any particular combination strategy was superior to the others.
      New, properly conducted, randomised controlled trials independent from the
      pharmaceutical industry need to recruit many more patients to give a reliable
      estimate of effect or of no effect of antipsychotics as combination treatment
      with clozapine in patients who do not have an optimal response to clozapine
      monotherapy.

PMID- 19588386
TI  - Topical glyceryl trinitrate for rotator cuff disease.
AB  - BACKGROUND: Rotator cuff disease is a common cause of shoulder pain. Topical
      glyceryl trinitrate is a possible new treatment. OBJECTIVES: To determine the
      effectiveness and safety of topical glyceryl trinitrate for rotator cuff disease.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, CINAHL, SPORTDiscus, PEDro, the Australian Clinical
      Trials Registry, Current Controlled Trials (to October 2007) and the references
      and citations of included studies. SELECTION CRITERIA: We included randomised
      controlled trials and controlled clinical trials of people with rotator cuff
      disease who received topical glyceryl trinitrate, alone or in combination,
      compared to placebo or active therapy. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed risk of bias and extracted data. MAIN RESULTS: Three small
      studies, one at moderate risk of bias and two at high risk of bias, were
      included. Meta-analysis was precluded due to different interventions and outcome
      measures. Study participants also had differing durations of symptoms and data
      for pain and function could only be extracted from one study. One placebo
      controlled trial (20 participants) tested 5 mg glyceryl trinitrate patches, used
      daily for three days, among participants with 'acute supraspinatus tendinitis' of
      less than seven days duration. Treatment resulted in reduced pain intensity
      (adjusted MD -3.50, 95% CI -3.96 to -3.04). Function was not measured. One trial
      (53 participants) compared one quarter of a 5 mg glyceryl trinitrate patch used
      daily for up to 24 weeks combined with rehabilitation to placebo patches and
      rehabilitation among participants with 'supraspinatus tendinopathy' for longer
      than six months. A third trial (48 participants) tested 5 mg glyceryl trinitrate
      patches, used daily for three days, compared to corticosteroid injection among
      participants with 'rotator cuff tendinitis' of less than six-weeks duration.
      Fifteen out of 24 participants in the glyceryl trinitrate treatment reported
      headache (RR 0.11, 95% CI 0.01 to 1.96). AUTHORS' CONCLUSIONS: There is some
      evidence from one study at high risk of bias that topical glyceryl trinitrate is
      more effective than placebo for rotator cuff disease among patients with acute
      symptoms (< seven-days duration), but there is insufficient evidence to be
      certain about their longer-term effects. Headache was a common side effect in one
      trial and any benefits of treatment need to be balanced against the risk of
      headache. Further high quality research is needed to determine the effectiveness
      and safety of this new therapy.

PMID- 19588387
TI  - Non-steroidal anti-inflammatory drugs for the common cold.
AB  - BACKGROUND: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been
      widely used for the treatment of pain and fever associated with the common cold,
      there is no systematic review to assess the effects of NSAIDs in patients with
      the common cold. OBJECTIVES: To determine the effects of NSAIDs versus placebo
      and other treatments on the signs and symptoms of the common cold. To determine
      any adverse effects of NSAIDs in patients treated with NSAIDs for the common
      cold. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2009, issue 1) which includes the Acute
      Respiratory Infections (ARI) Group's Specialized Register; MEDLINE (January 1966
      to March 2009); EMBASE (January 1980 to March 2009); CINAHL (January 1982 to
      March 2009); ProQuest Digital Dissertations (January 1938 to March 2009);
      KoreaMed (January 1958 to March 2009) and KMbase (January 1949 to March 2009).
      SELECTION CRITERIA: Randomized controlled trials (RCTs) studying treatment of the
      common cold with NSAIDs in adults or children. DATA COLLECTION AND ANALYSIS: Four
      review authors extracted data (SYK, YSM, YJC, YWH). We subdivided trials into
      placebo-controlled RCTs and NSAIDs versus NSAIDs RCTs. We extracted and
      summarized data on global efficacies: analgesic effects such as reduction of
      headache and myalgia; non-analgesic effects such as reduction of nasal symptoms,
      cough, sputum and sneezing; and side effects. MAIN RESULTS: This review includes
      nine RCTs, describing 37 comparisons: six were NSAIDs versus placebo, and three
      were NSAIDs versus NSAIDs. A total of 1064 patients with the common cold were
      included. In a pooled analysis, NSAIDs did not significantly reduce the total
      symptom score, or duration of colds.However, for outcomes related to the
      analgesic effects of NSAIDs (headache, ear pain, and muscle and joint pain)
      NSAIDs produced significant benefits, and malaise showed a borderline benefit,
      although throat irritation was not improved. Chills showed mixed results. For
      respiratory symptoms, cough and nasal discharge scores were not improved, but the
      sneezing score significantly improved. We found no evidence of increased
      frequency of adverse effects in the NSAID treatment groups. AUTHORS' CONCLUSIONS:
      The authors recommend NSAIDs for relieving discomfort or pain caused by the
      common cold. Further research is needed to investigate the effect of NSAIDs in
      relieving respiratory symptoms such as cough and nasal discharge.

PMID- 19588388
TI  - Interventions to prevent occupational noise induced hearing loss.
AB  - BACKGROUND: Millions of workers worldwide are exposed to noise levels that
      increase their risk of hearing impairment. Little is known about the
      effectiveness of hearing loss prevention interventions. OBJECTIVES: To assess the
      effectiveness of non-pharmaceutical interventions for preventing occupational
      noise exposure or occupational hearing loss compared to no intervention or
      alternative interventions. SEARCH STRATEGY: We searched the Cochrane Ear, Nose
      and Throat Disorders Group Trials Register; the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library issue 4, 2008); PubMed; EMBASE;
      CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts;
      NIOSHTIC, CISDOC and mRCT to 15 December 2008. SELECTION CRITERIA: Randomised
      controlled trials, controlled before-after studies and interrupted time series
      (ITS) of non-clinical hearing loss prevention interventions under field
      conditions among workers exposed to noise. DATA COLLECTION AND ANALYSIS: Two
      authors (EK, JV) independently assessed study eligibility and trial quality and
      extracted data. MAIN RESULTS: Twenty-one studies were included. One study
      evaluated a strategy to reduce noise exposure. Fourteen studies with 75,672
      participants evaluated hearing loss prevention programmes (HLPPs), and six
      studies with 169 participants evaluated hearing protection. The overall quality
      of studies was low.One ITS study evaluated the effect of new legislation in
      reducing noise exposure. It found that the median noise level decreased by 27.7
      dB(A) (95% confidence interval (CI) -36.1 to -19.3 dB) with a change in trend in
      time of -2.1 dB per year (95% CI -4.9 to 0.7).A hearing protection study in army
      recruits compared those exposed to impulse noise with non-exposed recruits. The
      odds ratio (OR) for hearing loss was 3.0 (95% CI 1.1 to 8.0) despite hearing
      protection. In four studies, workers in a HLPP had a 0.5 dB HL greater hearing
      loss at 4 kHz than non-noise exposed workers (95% CI -0.5 to 1.7). In one study,
      the hazard ratio of hearing loss was 3.8 (95% CI 2.7 to 5.3) for workers exposed
      to noise compared to non-exposed workers.In three studies, a high quality HLPP
      had a lower risk of hearing loss than lower quality programmes.Noise attenuation
      ratings of hearing protection under field conditions were consistently lower than
      the ratings provided by the manufacturers. AUTHORS' CONCLUSIONS: There is low
      quality evidence that legislation can reduce noise levels in workplaces.The
      effectiveness of hearing protection devices depends on their proper use. There is
      contradictory evidence that HLPPs are effective in the long-term. Even though
      case studies show that substantial reductions can be achieved, there is no
      evidence that this is realised in practice. Better implementation and
      reinforcement is needed.Better evaluations of technical interventions and long
      term effects are needed. Audiometric and noise measurement data are potentially
      valuable for such studies.

PMID- 19588390
TI  - Non-pharmacological interventions for assisting the induction of anaesthesia in
      children.
AB  - BACKGROUND: Induction of general anaesthesia can be distressing for children. Non
      pharmacological methods for reducing anxiety and improving co-operation may avoid
      the adverse effects of preoperative sedation. OBJECTIVES: To assess the effects
      of non-pharmacological interventions in assisting induction of anaesthesia in
      children by reducing their anxiety, distress or increasing their co-operation.
      SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2009, Issue 1). We
      searched the following databases from inception to 14th December 2008: MEDLINE,
      PsycINFO, CINAHL, DISSERTATION ABSTRACTS, Web of Science and EMBASE. SELECTION
      CRITERIA: We included randomized controlled trials of a non-pharmacological
      intervention implemented on the day of surgery or anaesthesia. DATA COLLECTION
      AND ANALYSIS: Two authors independently extracted data and assessed risk of bias
      in trials. MAIN RESULTS: We included 17 trials, all from developed countries,
      involving 1796 children, their parents or both. Eight trials assessed parental
      presence. None showed significant differences in anxiety or co-operation of
      children during induction, except for one where parental presence was
      significantly less effective than midazolam in reducing children's anxiety at
      induction. Six trials assessed interventions for children. Preparation with a
      computer package improved co-operation compared with parental presence (one
      trial). Children playing hand-held video games before induction were
      significantly less anxious than controls or premedicated children (one trial).
      Compared with controls, clown doctors reduced anxiety in children (modified Yale
      Preoperative Anxiety Scale (mYPAS): mean difference (MD) 30.75 95% CI 15.14 to
      46.36; one trial). In children undergoing hypnosis, there was a nonsignificant
      trend towards reduced anxiety during induction (mYPAS < 24: risk ratio (RR) 0.59
      95% CI 0.33 to 1.04 - 39% versus 68%: one trial) compared with midazolam. A low
      sensory environment improved children's co-operation at induction (RR 0.66, 95%
      CI 0.45 to 0.95; one trial) and no effect on children's anxiety was found for
      music therapy (one trial).Parental interventions were assessed in three trials.
      Children of parents having acupuncture compared with parental sham-acupuncture
      were less anxious during induction (mYPAS MD 17, 95% CI 3.49 to 30.51) and more
      children were co-operative (RR 0.63, 95% CI 0.4 to 0.99). Parental anxiety was
      also significantly reduced in this trial. In two trials, a video viewed
      preoperatively did not show effects on child or parental outcomes. AUTHORS'
      CONCLUSIONS: This review shows that the presence of parents during induction of
      general anaesthesia does not reduce their child's anxiety. Promising non
      pharmacological interventions such as parental acupuncture; clown doctors;
      hypnotherapy; low sensory stimulation; and hand-held video games needs to be
      investigated further.

PMID- 19588391
TI  - Traditional Chinese medicine for epilepsy.
AB  - BACKGROUND: Seizures are poorly controlled in many people with epilepsy, despite
      current antiepileptic treatments. Some turn to alternative or complementary
      therapy to treat their condition and the use of traditional Chinese medicinal
      herbs (TCMH) is increasingly popular. However, it remains unclear whether the
      existing evidence is rigorous enough to support its use. OBJECTIVES: To determine
      the effectiveness and safety of traditional Chinese medicine in people with
      epilepsy. SEARCH STRATEGY: Our search included the Cochrane Epilepsy Group's
      Specialised Register and the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1950 to 2007) and EMBASE
      (1974 to 2007). SELECTION CRITERIA: Randomised controlled trials evaluating
      traditional Chinese medicine in people of any age with any type of epilepsy, and
      comparing one formula of TCM with no intervention, placebo or single Western
      medicine (monotherapy). DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted trial data and assessed quality. We assessed the
      following outcomes: (a) seizure freedom for at least one year; (b) 50% or greater
      reduction in seizure frequency; (c) percentage reduction in seizure frequency and
      duration; and (d) adverse events. MAIN RESULTS: Five short-term studies involving
      1125 participants met the inclusion criteria. All the studies were of poor
      methodological quality and had a high probability of selection, detection and
      performance bias.Two studies assessed seizure freedom for one year. One found no
      difference between Xiaxingci granule and phenytoin for primary generalized tonic
      clonic seizures (RR 1.00; 95% CI 0.07 to 14.90).The other study found no
      difference between Dianxianning pill and valproate (RR 13.00; 95% CI 0.74 to
      227.72) for different types of epilepsy.Three studies assessed a 50% or greater
      reduction in seizure frequency. One found an advantage for Tianmadingxian capsule
      when compared to phenytoin (RR 1.37; 95% CI 1.23 to 1.53) in different types of
      epilepsy, the second an advantage for Zhixian I pill when compared to phenytoin
      (RR 1.31; 95% CI 1.16 to 1.48) in primary generalized tonic-clonic seizure, and
      the third an advantage for an 'Antiepilepsy capsule' when compared to
      phenobarbital (RR 1.21; 95% CI 1.02 to 1.43) for primary and secondary
      generalized tonic-clonic seizure. One study reported the incidence of adverse
      effects and the Peto odds ratio was 0.04 (99% CI 0.01 to 0.12, P < 0.00001)
      favouring TCMH compared to phenobarbital. AUTHORS' CONCLUSIONS: The current
      evidence is insufficient to support the use of traditional Chinese medicine as a
      treatment for epilepsy. Much larger, high quality randomised clinical trials are
      needed to evaluate the effectiveness and safety of traditional Chinese medicinal
      herbs for treating epilepsy.

PMID- 19588389
TI  - Deworming helminth co-infected individuals for delaying HIV disease progression.
AB  - BACKGROUND: The HIV-1 pandemic has disproportionately affected individuals in
      resource-constrained settings where other infectious diseases, such as helminth
      infections, also are highly prevalent. There are biologically plausible reasons
      for possible effects of helminth infection in HIV-1-infected individuals, and
      findings from multiple studies suggest that helminth infection may adversely
      affect HIV-1 progression. Since initial publication of this review (Walson 2007),
      additional data from randomized controlled trials (RCTs) has become available. We
      sought to evaluate all currently available evidence to determine if treatment of
      helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression.
      OBJECTIVES: To determine if treating helminth infection in individuals with HIV-1
      can reduce the progression of HIV-1 as determined by changes in CD4 count, viral
      load, or clinical disease progression. SEARCH STRATEGY: In this 2008 update, we
      searched online for published and unpublished studies in The Cochrane Library,
      MEDLINE, EMBASE, CENTRAL, and AIDSEARCH. We also searched databases listing
      conference abstracts, scanned reference lists of articles, and contacted authors
      of included studies. SELECTION CRITERIA: We searched for RCTs and quasi-RCTs that
      compared HIV-1 progression as measured by changes in CD4 count, viral load, or
      clinical disease progression in HIV-1 infected individuals receiving anti
      helminthic therapy. DATA COLLECTION AND ANALYSIS: Data regarding changes in CD4
      count, HIV-1 RNA levels, and/or clinical staging after treatment of helminth co
      infection were extracted from identified studies. MAIN RESULTS: Of 7,019
      abstracts identified (6,384 from original searches plus 635 from updated
      searches), 17 abstracts were identified as meeting criteria for potential
      inclusion (15 from previous review plus an additional two RCTs). After
      restricting inclusion to RCTs, a total of three studies were eligible for
      inclusion in this updated review.All three trials showed individual beneficial
      effects of helminth eradication on markers of HIV-1 disease progression (HIV-1
      RNA and/or CD4 counts). When data from these trials were pooled, the analysis
      demonstrated significant benefit of deworming on both plasma HIV-1 RNA and CD4
      counts. AUTHORS' CONCLUSIONS: To date, three RCTs have evaluated the effects of
      deworming on markers of HIV-1 disease progression in helminth and HIV-1 co
      infected individuals. All trials demonstrate benefit in attenuating or reducing
      plasma viral load and/or increasing CD4 counts. When taken together, there is
      evidence of benefit for deworming HIV-1 co-infected adults. Given that these
      studies evaluated different helminth species and different interventions, further
      trials are warranted to evaluate species-specific effects and to document long
      term clinical outcomes following deworming.

PMID- 19588392
TI  - Therapeutic interventions for disease progression in Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disease with an average onset between the fourth and fifth decade of life; it
      leads to death 15 to 20 years after the onset of symptoms. Although several drugs
      seem effective in controlling the incapacitating manifestations of HD, no
      specific therapy is known. The present review aims at analysing the best
      available data on therapeutic interventions investigated with the goal of
      modifying the progression of the disease as measured in terms of survival,
      disability or progression of HD core symptoms. OBJECTIVES: Evaluate the
      effectiveness of therapeutic interventions aimed at modifying disease progression
      in HD. SEARCH STRATEGY: The search strategy developed for the Movement Disorders
      Group was undertaken. The Cochrane Controlled Trials Register, Medline, EMBASE
      and Clinical Trials Database of the United States National Institute of Health
      were thoroughly searched until December 2007. SELECTION CRITERIA: All randomised,
      double-blinded, placebo-controlled clinical trials of therapeutics investigated
      with the goal of modifying disease progression in HD were included. Participants
      should have genetically confirmed diagnosis of HD or compatible symptoms and a
      family history. Trials had a follow-up duration of more than three months and at
      least ten participants. All pharmacological and non-pharmacological interventions
      were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      the eligibility of identified trials. The methodological quality was assessed and
      eligible data were registered onto standardised forms. An intention-to-treat
      analysis was conducted, when feasible. If data were not available in the original
      publication, the principal investigator of the trial was contacted for further
      information. A meta-analysis was to be conducted when possible; otherwise, a
      descriptive summary of the results was provided. The software Revman 5.0.15 was
      used for statistical analysis. MAIN RESULTS: Eight trials were included involving
      a total of 1366 HD patients. The duration of the studies ranged between 30 and
      144 weeks (median: 52 weeks). The following interventions were selected: vitamin
      E, Idebenone, Baclofen, Lamotrigine, creatine, coenzyme Q10 + Remacemide, ethyl
      eicosapentanoic acid and Riluzole. No trials produced positive results for the
      selected efficacy outcome measures. A descriptive summary of the trials is
      provided. The selected interventions were found to be generally safe and well
      tolerated. AUTHORS' CONCLUSIONS: Only pharmacological interventions were included
      and none proved to be effective as a disease-modifying therapy for HD. Further
      trials with greater methodological quality should be conducted using more
      sensitive biological markers. Pre-symptomatic mutation carriers should be
      included in future studies.

PMID- 19588393
TI  - Therapeutic interventions for symptomatic treatment in Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is an orphan autosomal dominant
      neurodegenerative disorder caused by the amplification of a nucleic acids triplet
      repeat. It is characterised by core symptoms of chorea, progressive dementia and
      psychiatric manifestations such as depression, irritability, apathy and
      psychosis. In current clinical practice, drugs exist that seem to improve
      symptoms for HD patients. However, their effectiveness has not been fully
      measured. OBJECTIVES: To evaluate the effectiveness of the available
      interventions for the symptomatic treatment of HD. SEARCH STRATEGY: The search
      strategy developed for the Movement Disorders Group was undertaken. Cochrane
      Controlled Trials Register, Medline, EMBASE and Clinical Trials Database of the
      United States National Institute of Health were thoroughly searched up until
      December 2007. SELECTION CRITERIA: All randomised, double-blinded, placebo
      controlled clinical trials conducted on any symptomatic therapy used for HD with
      at least ten participants were included. Participants should have HD clinical
      features and a confirmatory genetic diagnosis or a compatible family history. All
      disease variants and ages of disease onset were included. Cross-over studies were
      included. All pharmacological and non-pharmacological interventions aimed at the
      control of signs and symptoms associated with HD were to be selected. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed the identified
      trials for eligibility. In the selected trials, the assessment of their
      methodological quality was done according to the Cochrane Collaboration handbook,
      and eligible data were registered onto standardised forms. If possible, an
      intention-to-treat analysis was conducted. When data were not available in the
      original publication, the principal investigator of the trial was contacted. A
      meta-analysis was conducted when possible and otherwise the descriptive summary
      of the results was provided. The software Revman 5.0.15 was used for statistical
      analysis. MAIN RESULTS: 22 trials (1254 participants) were included. Nine trials
      had a cross-over design and 13 were conducted in parallel. Study duration ranged
      from 2 to 80 weeks. Various pharmacological interventions were studied, mostly,
      they were anti-dopaminergic drugs (n = 5), glutamate receptor antagonists (n = 5)
      and energy metabolites (n = 5). Only tetrabenazine showed a clear efficacy for
      the control of chorea. The remaining pharmacological interventions revealed no
      clear effectiveness. AUTHORS' CONCLUSIONS: No intervention proved to have a
      consistent symptomatic control in HD. Tetrabenazine is the anti-choreic drug with
      the best quality data available. Other symptomatic areas should be explored by
      well-designed randomised placebo-controlled studies.

PMID- 19588394
TI  - Mono and multifaceted inhalant and/or food allergen reduction interventions for
      preventing asthma in children at high risk of developing asthma.
AB  - BACKGROUND: Allergen exposure is one of the environmental factors seemingly
      associated with the development of asthma. If asthma is a multi-factorial
      disease, it is hypothesised that prevention might only prove effective if most or
      all relevant environmental factors are simultaneously avoided. OBJECTIVES: To
      assess effect(s) of monofaceted and multifaceted interventions compared with
      control interventions in preventing asthma and asthma symptoms in high risk
      children. SEARCH STRATEGY: We searched the Cochrane Airways Trials Register
      (December 2008). SELECTION CRITERIA: Randomised controlled trials of allergen
      exposure reduction for the primary prevention of asthma in children.
      Interventions were multifaceted (reducing exposure to both inhalant and food
      allergens) or monofaceted (reducing exposure to either inhalant or food
      allergens) Follow up had to be from birth (or during pregnancy) up to a minimum
      of two years of age. DATA COLLECTION AND ANALYSIS: We included in the analysis
      studies assessing the primary outcome (current diagnosis: asthma) and/or one of
      the secondary outcomes (current respiratory symptoms: wheezing, nocturnal
      coughing and dyspnoea). We pooled multifaceted and monofaceted intervention
      trials separately. We made an indirect comparison of their effects using tests
      for interaction to calculate relative odds ratios. MAIN RESULTS: We included
      three multifaceted and six monofaceted intervention studies (3271 children).
      Physician diagnosed asthma in children less than five years, and asthma as
      defined by respiratory symptoms and lung function criteria in children aged five
      years and older, both favoured treatment with a multifaceted intervention
      compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval
      (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there
      was no significant difference in outcome between monofaceted intervention and
      control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR
      0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not
      demonstrate a significant difference between multiple interventions and mono
      interventions in reducing the frequency of asthma diagnosis in children under
      five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and
      older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no
      significant difference between either mono- and multifaceted intervention and
      control in reducing the likelihood of symptoms of nocturnal coughing at follow
      up. Wheezing, however, showed a significant difference between multifaceted and
      mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the
      significance was lost when data on treatment only was analysed. AUTHORS'
      CONCLUSIONS: The available evidence suggests that the reduction of exposure to
      multiple allergens compared to usual care reduces the likelihood of a current
      diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono
      intervention studies have not produced effects which are statistically
      significant compared with control. In children who are at risk of developing
      childhood asthma, multifaceted interventions, characterised by dietary allergen
      reduction and environmental remediation, reduce the odds of a physician diagnosis
      of asthma later in childhood by half. This translates to a number needed to treat
      (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze
      was inconsistent and had no significant impact on nocturnal coughing or dyspnoea.
      Data from monofaceted intervention exposed children studies were not
      significantly different from those of control groups for all outcomes. There
      remains uncertainty as to whether multiple interventions are more effective than
      mono-component interventions. The comparisons made were indirect, making the
      conclusions drawn uncertain. To our knowledge there are no ongoing studies in
      which both intervention strategies are randomly compared. The findings, however,
      warrant further direct comparison between multiple- and monofaceted interventions
      aimed at reducing the prevalence of asthma in children.

PMID- 19588395
TI  - Immunotherapy for diabetic amyotrophy.
AB  - BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or
      subacute, progressive, asymmetrical pain and weakness of the proximal lower limb
      muscles. The various names for the condition include diabetic amyotrophy, or
      diabetic lumbosacral radiculoplexus neuropathies. Some studies suggest that it
      may be due to immune-mediated inflammatory microvasculitis causing ischaemic
      damage of the nerves. Immunotherapies would therefore be expected to be
      beneficial. OBJECTIVES: We aimed to review the evidence from randomised trials
      for the efficacy of any form of immunotherapy in the treatment of diabetic
      amyotrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      Trials Register (searched April 2 2009), MEDLINE (searched January 1966 to April
      2 2009), EMBASE (searched January 1980 to April 2 2009) and contacted authors of
      relevant publications and other experts to obtain additional references,
      unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to
      include all randomised and quasi-randomised trials of any immunotherapy in
      participants with the condition fulfilling all the following: diabetes mellitus
      as defined by internationally recognised criteria, acute or subacute onset of
      pain and lower motor neuron weakness involving predominantly the proximal muscles
      of the lower limbs, weakness that is not confined to one nerve or nerve root
      distribution and exclusion of other causes of lumbosacral radiculopathies and
      plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all
      references retrieved by the search to select those meeting the inclusion
      criteria. MAIN RESULTS: We found only one completed controlled trial using
      intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results
      have not been fully published and were not available for analyses. AUTHORS'
      CONCLUSIONS: There is presently no evidence from randomised trials to support any
      recommendation on the use of any immunotherapy treatment in diabetic amyotrophy.

PMID- 19588397
TI  - Laser treatment of drusen to prevent progression to advanced age-related macular
      degeneration.
AB  - BACKGROUND: Drusen are amorphous yellowish deposits beneath the sensory retina.
      People with drusen, particularly large drusen, are at higher risk of developing
      age-related macular degeneration (AMD). The most common complication in AMD is
      choroidal neovascularisation (CNV), the growth of new blood vessels in the centre
      of the macula. The risk of CNV is higher among patients who are already affected
      by CNV in one eye.It has been observed clinically that laser photocoagulation of
      drusen leads to their disappearance and may prevent the occurrence of advanced
      disease (CNV or geographic atrophy) associated with visual loss. OBJECTIVES: To
      examine the effectiveness and adverse effects of laser photocoagulation of drusen
      in AMD. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE on 14 November
      2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of laser treatment
      of drusen in AMD in which laser treatment had been compared with no intervention
      or sham treatment. Two types of trials were included. Some trials studied one eye
      of each patient (unilateral studies); other studies recruited patients with
      bilateral drusen and randomised one eye to photocoagulation or control and the
      fellow eye to the other group. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected studies and extracted data. We pooled data from unilateral
      and bilateral studies using a random-effects model. For the bilateral studies, we
      estimated the within-patient correlation coefficient from one study and assumed
      it was valid for the others. MAIN RESULTS: We found nine studies which randomised
      2216 people: four unilateral trials, three bilateral trials and two trials that
      included both a unilateral and a bilateral study arm.Overall, the studies were of
      moderate quality. Only half of the trials reported adequate allocation sequence
      generation, allocation concealment and masking of visual acuity outcome
      assessors.Although two (of the nine) studies reported significant drusen
      disappearance at two years, photocoagulation did not appear to affect the
      development of CNV at two years follow up (nine studies, 1767 people followed up,
      odds ratio (OR) 1.04, 95% CI 0.71 to 1.51) or the loss of three or more lines of
      visual acuity (six studies, 1628 people followed up, OR 1.17, 95% CI 0.75 to
      1.82). AUTHORS' CONCLUSIONS: The trials included in this review confirm the
      clinical observation that laser photocoagulation of drusen leads to their
      disappearance. However, there is no evidence that this subsequently results in a
      reduction in the risk of developing CNV, geographic atrophy or visual acuity
      loss.

PMID- 19588396
TI  - Milnacipran versus other antidepressive agents for depression.
AB  - BACKGROUND: Although pharmacological and psychological interventions are both
      effective for major depression, antidepressant drugs are frequently used as first
      line treatment in primary and secondary care settings. Milnacipran, a dual
      serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant
      drugs that clinicians use for routine depression care. OBJECTIVES: To assess the
      evidence for the efficacy, acceptability and tolerability of milnacipran in
      comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other
      newer antidepressive agents in the acute-phase treatment of major depression.
      SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety & Neurosis review
      group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were
      electronically searched in August 2008. References of relevant trials and other
      reviews were also checked. Trial databases of the drug-approving agencies and
      ongoing clinical trial registers for all published and unpublished trials were
      hand-searched in 2007. All relevant authors were contacted for supplemental data.
      No language restriction was applied. SELECTION CRITERIA: Randomised controlled
      trials comparing milnacipran with any other active antidepressive agents
      (including non-conventional agents such as herbal products like hypericum) as
      monotherapy in the acute phase of major depression were selected. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently checked eligibility, assessed
      methodological quality and extracted data from the eligible trials using a
      standardised data extraction form. The number of participants who responded to
      treatment or those who achieved remission were calculated on an intention-to
      treat basis. Random-effects meta-analyses were conducted, combining data from the
      included trials. MAIN RESULTS: A total of 16 randomised controlled trials
      (n=2277) were included in the meta-analysis.Despite the size of this sample, the
      pooled 95% confidence intervals were rather wide and there were no statistically
      significant differences in efficacy, acceptability and tolerability when
      comparing milnacipran with other antidepressive agents. However, compared with
      TCAs, patients taking milnacipran were associated with fewer dropouts due to
      adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence
      to suggest that patients taking milnacipran experienced fewer adverse events of
      sleepiness/ drowsiness, dry mouth or constipation compared with TCAs. AUTHORS'
      CONCLUSIONS: Currently, there is inadequate evidence to conclude whether
      milnacipran is superior, inferior or the same as other antidepressive agents in
      terms of efficacy, acceptability and tolerability in the acute phase treatment of
      major depression. However, there is some evidence in favour of milnacipran over
      TCAs in terms of dropouts due to adverse events (acceptability) and the rates of
      experiencing adverse events (tolerability). Information about other clinically
      meaningful outcomes such as cost-effectiveness and social functioning, including
      the ability to return to work, is lacking. Further study is needed to answer
      whether milnacipran would be the better choice of antidepressant for acute major
      depression.

PMID- 19588398
TI  - Chinese herbal medicine for endometriosis.
AB  - BACKGROUND: Endometriosis is characterized by the presence of tissue that is
      morphologically and biologically similar to normal endometrium in locations
      outside the uterus. Surgical and hormonal treatment of endometriosis have
      unpleasant side effects and high rates of relapse. In China, treatment of
      endometriosis using Chinese herbal medicine (CHM) is routine and considerable
      research into the role of CHM in alleviating pain, promoting fertility, and
      preventing relapse has taken place. OBJECTIVES: To review the effectiveness and
      safety of CHM in alleviating endometriosis-related pain and infertility. SEARCH
      STRATEGY: We searched the Menstrual Disorders and Subfertility Group Trials
      Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library) and the following English language electronic databases (from their
      inception to the present): MEDLINE, EMBASE, AMED, CINAHL, NLH on the 30/04/09.We
      also searched Chinese language electronic databases: Chinese Biomedical
      Literature Database (CBM), China National Knowledge Infrastructure (CNKI),
      Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature
      Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents
      (CMCC). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving CHM
      versus placebo, biomedical treatment, another CHM intervention, or CHM plus
      biomedical treatment versus biomedical treatment were selected. Only trials with
      confirmed randomisation procedures and laparoscopic diagnosis of endometriosis
      were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment, and data
      extraction and analysis were performed independently by three review authors.
      Data were combined for meta-analysis using relative risk (RR) for dichotomous
      data. A fixed-effect statistical model was used, where appropriate. Data not
      suitable for meta-analysis are presented as descriptive data. MAIN RESULTS: Two
      Chinese RCTs involving 158 women were included in this review. Both these trials
      described adequate methodology. Neither trial compared CHM with placebo
      treatment.There was no evidence of a significant difference in rates of
      symptomatic relief between CHM and gestrinone administered subsequent to
      laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence
      interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed
      no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18).
      There was no significant difference between the CHM and gestrinone groups with
      regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to
      1.59, one RCT).CHM administered orally and then in conjunction with a herbal
      enema resulted in a greater proportion of women obtaining symptomatic relief than
      with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54,
      respectively).Overall, 100% of women in all the groups showed some improvement in
      their symptoms.Oral plus enema administration of CHM showed a greater reduction
      in average dysmenorrhoea pain scores than did danazol (mean difference (MD) 
      2.90, 95% CI -4.55 to -1.25; P < 0.01).Combined oral and enema administration of
      CHM showed a greater improvement, measured as the disappearance or shrinkage of
      adnexal masses, than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral
      pain, rectal discomfort, or vaginal nodules tenderness, there was no significant
      difference either between CHM and danazol. AUTHORS' CONCLUSIONS: Post-surgical
      administration of CHM may have comparable benefits to gestrinone but with fewer
      side effects. Oral CHM may have a better overall treatment effect than danazol;
      it may be more effective in relieving dysmenorrhea and shrinking adnexal masses
      when used in conjunction with a CHM enema. However, more rigorous research is
      required to accurately assess the potential role of CHM in treating
      endometriosis.

PMID- 19588399
TI  - Oral iron supplementation for preventing or treating anaemia among children in
      malaria-endemic areas.
AB  - BACKGROUND: Iron-deficiency anaemia is common during childhood. Iron
      supplementation has been claimed to increase the risk of malaria. OBJECTIVES: To
      assess the effect of iron on malaria and deaths. SEARCH STRATEGY: We searched The
      Cochrane Library (2009, issue 1); MEDLINE; EMBASE; LILACS and metaRegister of
      Controlled Trials, all up to March 2009. We scanned references of included
      trials. SELECTION CRITERIA: Individually and cluster-randomized controlled trials
      conducted in hypoendemic to holoendemic malaria regions and including children <
      18 years. We included trials comparing orally administered iron with or without
      folic acid vs. placebo or no treatment. Iron fortification was excluded.
      Antimalarials and/or antiparasitics could be administered to either group.
      Additional micronutrients could only be administered equally to both groups. DATA
      COLLECTION AND ANALYSIS: The primary outcomes were malaria-related events and
      deaths. Secondary outcomes included haemoglobin, anaemia, other infections,
      growth, hospitalizations, and clinic visits. We assessed risk of bias using
      domain-based evaluation. Two authors independently selected studies and extracted
      data. We contacted authors for missing data. We assessed heterogeneity. We
      performed fixed-effect meta-analysis and presented random-effects results when
      heterogeneity was present. We present pooled risk ratios (RR) with 95% confidence
      intervals (CIs). We used adjusted analyses for cluster-randomized trials. MAIN
      RESULTS: Sixty-eight trials (42,981 children) fulfilled the inclusion criteria.
      Iron supplementation did not increase the risk of clinical malaria (RR 1.00, 95%
      CI 0.88 to 1.13; 22,724 children, 14 trials, random-effects model). The risk was
      similar among children who were non-anaemic at baseline (RR 0.96, 95% CI 0.85 to
      1.09). An increased risk of malaria with iron was observed in trials that did not
      provide malaria surveillance and treatment. The risk of malaria parasitaemia was
      higher with iron (RR 1.13, 95% CI 1.01 to 1.26), but there was no difference in
      adequately concealed trials. Iron + antimalarial was protective for malaria (four
      trials). Iron did not increase the risk of parasitological failure when given
      during malaria (three trials). There was no increased risk of death across all
      trials comparing iron versus placebo (RR 1.11, 95% CI 0.91 to 1.36; 21,272
      children, 12 trials). Iron supplementation increased haemoglobin, with
      significant heterogeneity, and malaria endemicity did not affect this effect.
      Growth and other infections were mostly not affected by iron supplementation.
      AUTHORS' CONCLUSIONS: Iron does not increase the risk of clinical malaria or
      death, when regular malaria surveillance and treatment services are provided.
      There is no need to screen for anaemia prior to iron supplementation.

PMID- 19588400
TI  - Interventions for replacing missing teeth: 1- versus 2-stage implant placement.
AB  - BACKGROUND: Implants may be placed penetrating the oral mucosa (1-stage
      procedure) or can be completely buried under the oral mucosa (2-stage procedure)
      during the healing phase of the bone at the implant surface. With a 2-stage
      procedure the risk of having unwanted loading onto the implants is minimized, but
      a second minor surgical intervention is needed to connect the healing abutments
      and more time is needed prior to start the prosthetic phase because of the wound
      healing period required in relation to the second surgical intervention.
      OBJECTIVES: To evaluate whether a 1-stage implant placement procedure is as
      effective as a 2-stage procedure. SEARCH STRATEGY: The Cochrane Oral Health
      Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched. Handsearching
      included several dental journals. Authors of all identified trials, an Internet
      discussion group and 55 dental implant manufacturers were contacted to find
      unpublished randomised controlled trials (RCTs). The last electronic search was
      conducted on 21 January 2009. SELECTION CRITERIA: All RCTs of osseointegrated
      dental implants comparing the same dental implants placed according to 1- versus
      2-stage procedures with a minimum follow up of 6 months after loading. Outcome
      measures were: prosthesis failures, implant failures, marginal bone level changes
      on intraoral radiographs, patient preference including aesthetics, aesthetics
      evaluated by dentists, and complications. DATA COLLECTION AND ANALYSIS: Screening
      of eligible studies, assessment of the methodological quality of the trials and
      data extraction were conducted in duplicate and independently by two review
      authors. Authors were contacted for missing information. Results were expressed
      as random-effects models using mean differences for continuous outcomes and risk
      ratios for dichotomous outcomes with 95% confidence intervals. MAIN RESULTS: Five
      RCTs were identified and included reporting data on 239 patients in total. On a
      patient, rather than per implant basis, the meta-analyses showed no statistically
      significant differences for prosthesis and implant failures, though trends,
      especially in fully edentulous patients, favoured 2-stage (submerged) implants.
      AUTHORS' CONCLUSIONS: The number of patients included in the trials was too small
      to draw definitive conclusions. The 1-stage approach might be preferable in
      partially edentulous patients since it avoids one surgical intervention and
      shortens treatment times, while a 2-stage submerged approach could be indicated
      when an implant has not obtained an optimal primary stability or when barriers
      are used for guided tissue regeneration, or when it is expected that removable
      temporary prostheses could transmit excessive forces on the penetrating abutments
      especially in fully edentulous patients.

PMID- 19588401
TI  - Percutaneous ethanol injection or percutaneous acetic acid injection for early
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common global
      cancer. When HCC is detected early, interventions such as percutaneous ethanol
      injection (PEI), percutaneous acetic acid injection (PAI), and radiofrequency
      thermal ablation (RFTA) have curative potential and represent low invasive
      alternatives to surgery. The role of PEI or PAI has not been addressed in a
      systematic review. OBJECTIVES: To evaluate the beneficial and harmful effects of
      PEI or PAI in adults with early HCC. SEARCH STRATEGY: A systematic search was
      performed in The Cochrane Hepato-Biliary Group Controlled Trials Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, EMBASE, and ISI Web of Science in May 2009. Meeting abstracts of six
      oncological and hepatological societies (ASCO, ESMO, ECCO, AASLD, EASL, APASL)
      and references of articles were handsearched. Researchers in the field were
      contacted. SELECTION CRITERIA: Randomised trials comparing PEI or PAI with no
      intervention, sham intervention, other percutaneous interventions or surgery for
      the treatment of early HCC were considered regardless of blinding, publication
      status, or language. Studies comparing RFTA or combination treatments were
      excluded. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials
      for inclusion, and extracted and analysed data. The hazard ratios for median
      overall survival and recurrence-free survival were calculated using the Cox
      regression model with Parmar's method. Type and number of adverse events were
      reported descriptively. MAIN RESULTS: Three randomised trials with a total of 261
      patients were eligible for inclusion. The risk of bias was high in all trials.
      Two of the trials compared PEI with PAI. Overall survival (HR 1.47; 95%
      confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95%
      CI 0.68 to 2.94) were not significantly different. Data on the duration of
      hospital stay were inconclusive. Data on quality of life were not available.
      There were only mild adverse events in both treatment modalities.The other trial
      compared PEI with surgery. There was no significant difference in overall
      survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35;
      95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group.
      Three postoperative deaths occurred in the surgery group. AUTHORS' CONCLUSIONS:
      PEI and PAI does not differ significantly regarding benefits and harms in
      patients with early HCC, but only a limited number of patients have been examined
      and the bias risk was high in all trials. There is also insufficient evidence to
      determine whether PEI or segmental liver resection is more effective, although
      PEI may seem safer.

PMID- 19588402
TI  - Social norms interventions to reduce alcohol misuse in university or college
      students.
AB  - BACKGROUND: Drinking is influenced by youth (mis)perceptions of how their peers
      drink. If misperceptions can be corrected, young people may drink less.
      OBJECTIVES: To determine whether social norms feedback reduces alcohol misuse in
      university or college students. SEARCH STRATEGY: Cochrane Drugs and Alcohol Group
      Register of Trials; Central; MEDLINE; EMBASE; PsyInfo; CINAHL (up to March 2008).
      SELECTION CRITERIA: RCT or cluster RCT that evaluate social normative
      intervention with no intervention, alcohol education leaflet or other non
      normative feedback intervention DATA COLLECTION AND ANALYSIS: 2/3 authors
      extracted data. Included studies were assessed against criteria indicated in the
      Cochrane Reviewers Handbook version 5.0.0. MAIN RESULTS: Twenty-two studies were
      included (7,275 participants).Alcohol related problems: Significant reduction
      with Web/computer feedback (WF) (SMD -0.31 95% Cl -0.59 to -0.02), three studies,
      278 participants. No significant effect of mailed feedback (MF), individual face
      to-face feedback (IFF) or group face-to-face feedback (GFF).Peak Blood Alcohol
      Content (BAC) : Significant reduction with WF (SMD -0.77 95% Cl -1.25 to -0.28),
      two studies, 198 participants. No significant effect of MF or IFF.Drinking
      Frequency: Significant reduction with WF (SMD -0.38 95% Cl -0.63 to -0.13), two
      studies, 243 participants and IFF (SMD -0.39 95% Cl -0.66 to -0.12), two studies,
      217 participants. No significant effect of MF.Drinking Quantity: Significant
      reduction with WF (SMD -0.35 95% Cl -0.51 to -0.18), five studies, 556
      participants and GFF (SMD -0.32 95% Cl -0.63 to -0.02) three studies, 173
      participants. No significant effect of MF or IF.Binge drinking: Significant
      reduction with WF (SMD -0.47 95% Cl -0.92 to -0.03) one study, 80 participants,
      IFF (SMD -0.25 95% Cl -0.49 to -0.02) three studies, 278 participants and and GFF
      (SMD -0.38 95% Cl -0.62 to -0.14) four studies, 264 participants. No significant
      effect for MF.BAC: No significant effect of MF and IFFDrinking norms: Significant
      reduction with WF (SMD -0.75 95% Cl -0.98 to -0.52 ) three studies, 312
      participants. AUTHORS' CONCLUSIONS: WF and IFF are probably effective in reducing
      alcohol misuse. No direct comparisons of WF against IFF were found, but WF
      impacted across a broader set of outcomes and is less costly so therefore might
      be preferred. Significant effects were more apparent for short-term outcomes (up
      to three months). For mailed and group feedback, and social norms marketing
      campaigns, the results are on the whole not significant and therefore cannot be
      recommended.

PMID- 19588403
TI  - Maternity waiting facilities for improving maternal and neonatal outcome in low
      resource countries.
AB  - BACKGROUND: A Maternity Waiting Home (MWH) is a facility, within easy reach of a
      hospital or health centre which provides Emergency Obstetric Care (EmOC). Women
      may stay in the MWH at the end of their pregnancy and await labour. Once labour
      starts, women move to the health facility so that labour and giving birth may be
      assisted by a skilled birth attendant. The aim of the MWH is to improve
      accessibility and thus reduce morbidity and mortality for mother and neonate
      should complications arise. Some studies report a favourable effect on the
      outcomes for women and their newborn. Others show that utilisation is low and
      barriers exist. However these data are limited in reliability. OBJECTIVES: To
      assess the effects of a maternity waiting facility on maternal and perinatal
      health. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (April 2009), CENTRAL (The Cochrane Library 2009, Issue
      1), MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), CINAHL (1982 to
      April 2009), African Journals Online (AJOL) (April 2009), POPLINE (April 2009),
      Dissertation Abstracts (April 2009) and the National Research Register archive
      (March 2008). SELECTION CRITERIA: Randomised controlled trials including quasi
      randomised and cluster-randomised trials that compared perinatal and maternal
      outcome in women using a MWH and women who did not. DATA COLLECTION AND ANALYSIS:
      There were no randomised controlled trials or cluster-randomised trials
      identified from the search. MAIN RESULTS: There were no randomised controlled
      trials or cluster-randomised trials identified from the search. AUTHORS'
      CONCLUSIONS: There is insufficient evidence to determine the effectiveness of
      Maternity Waiting Facilities for improving maternal and neonatal outcomes.

PMID- 19588405
TI  - Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot
      infections.
AB  - BACKGROUND: G-CSF increases the release of neutrophil endothelial progenitor
      cells from the bone marrow, and improves neutrophil functions, which are often
      impaired in people with diabetes. OBJECTIVES: To examine the effects of
      adjunctive G-CSF compared with placebo or no growth factor added to usual care on
      rates of infection, cure and wound healing in people with diabetes who have a
      foot infection. SEARCH STRATEGY: We searched the Cochrane Wounds Group
      Specialised Register (Searched 16/3/09); the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, issue 1 2009); Ovid MEDLINE (1950 to
      March Week 1 2009); Ovid EMBASE (1980 to 2009 Week 11); EBSCO CINAHL (1982 to
      March Week 2 2009); LookSmart's Find Articles (January 1990 to January 2008);
      conference proceedings and references lists in the included studies. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) that evaluated the effect of adding
      G-CSF to usual care in people with a diabetic foot infection. DATA COLLECTION AND
      ANALYSIS: Three review authors independently assessed trial eligibility,
      methodological quality and extracted data. Relative risk (RR), or for continuous
      outcomes, mean differences (MD), with 95% confidence intervals (CI) were
      reported. In the case of low or no heterogeneity studies were pooled using a
      fixed-effect model. MAIN RESULTS: We identified and included five eligible trials
      with a total of 167 patients. The investigators administered various G-CSF
      preparations, at different doses and for different durations of time. Adding G
      CSF did not significantly affect the likelihood of resolution of infection or
      wound healing, but it was associated with a significantly reduced likelihood of
      lower extremity surgical interventions (RR 0.37; 95 % CI 0.20 to 0.68), including
      amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the
      duration of hospital stay (MD, -1.40 days; 95 % CI, -2.27 to -0.53 days), but did
      not significantly affect the duration of systemic antibiotic therapy (MD, -0.27
      days; 95 % CI, -1.30 to 0.77 days). AUTHORS' CONCLUSIONS: The available evidence
      is limited, but suggests that adjunctive G-CSF treatment in people with a
      diabetic foot infection, including infected ulcers, does not appear to increase
      the likelihood of resolution of infection or healing of the foot ulcer. However,
      it does appear to reduce the need for surgical interventions, especially
      amputations, and the duration of hospitalisation. Clinicians might consider
      adding G-CSF to the usual treatment of diabetic foot infections, especially in
      patients with a limb-threatening infection, but it is not clear which patients
      might benefit.

PMID- 19588404
TI  - Peri-operative glycaemic control regimens for preventing surgical site infections
      in adults.
AB  - BACKGROUND: Surgical site infections (SSIs) are associated with significant
      morbidity, mortality, and resource utilization and are potentially preventable.
      Peri-operative hyperglycaemia has been associated with increased SSIs and
      previous recommendations have been to treat glucose levels above 200 mg/dL.
      However, recent studies have questioned the optimal glycaemic control regimen to
      prevent SSIs. Whether the benefits of strict or intensive glycaemic control with
      insulin infusion as compared to conventional management outweigh the risks
      remains controversial. OBJECTIVES: To summarise the evidence for the impact of
      glycaemic control in the peri-operative period on the incidence of surgical site
      infections, hypoglycaemia, level of glycaemic control, all-cause and infection
      related mortality, and hospital length of stay and to investigate for differences
      of effect between different levels of glycaemic control. SEARCH STRATEGY: A
      search strategy was developed to search the following databases: Cochrane Wounds
      Group Specialised Register (searched 25 March 2009), The Cochrane Central
      Register of Controlled Trials, The Cochrane Library 2009, Issue 1; Ovid MEDLINE
      (1950 to March Week 2 2009); Ovid EMBASE (1980 to 2009 Week 12) and EBSCO CINAHL
      (1982 to March Week 3 2009). The search was not limited by language or
      publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) were
      eligible for inclusion if they evaluated two (or more) glycaemic control regimens
      in the peri-operative period (within one week pre-, intra-, and/or post
      operative) and reported surgical site infections as an outcome. DATA COLLECTION
      AND ANALYSIS: The standard method for conducting a systematic review in
      accordance with the Cochrane Wounds Group was used. Two review authors
      independently reviewed the results from the database searches and identified
      relevant studies. Two review authors extracted study data and outcomes from each
      study and reviewed each study for methodological quality. Any disagreement was
      resolved by discussion or by referral to a third review author. MAIN RESULTS:
      Five RCTs met the pre-specified inclusion criteria for this review. No trials
      evaluated strict glycaemic control in the immediate pre-operative period or
      outside the intensive care unit. Due to heterogeneity in patient populations,
      peri-operative period, glycaemic target, route of insulin administration, and
      definitions of outcome measures, combination of the results of the five included
      trials into a meta-analysis was not appropriate. The methodological quality of
      the trials was variable. In terms of outcomes, only one trial demonstrated a
      significant reduction in SSIs with strict glycaemic control, but the quality of
      this trial was difficult to assess as a result of poor reporting; furthermore the
      baseline rate of SSIs was high (30%). The other trials were either underpowered
      to detect a difference in SSIs, due to a low baseline rate (less than or equal to
      5%), or did not report SSIs as a single outcome but as part of a composite. Of
      the three trials reporting hypoglycaemia (which was not consistently defined) all
      had a higher rate in the strict glycaemic control group but none attributed
      significant morbidity to the hypoglycaemia. Adequacy of glucose control between
      groups was measured differently among studies. Studies could not be compared due
      to differences in target ranges, and were susceptible to measurement bias due to
      differences in frequency of measurement and lack of blinding by the providers
      following the glycaemic protocols. Infection-related mortality was not reported
      in any of the trials, and no trials demonstrated a significant difference in all
      cause mortality. Length of hospital stay was significantly reduced in the strict
      glycaemic control groups in only one trial. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support strict glycaemic control versus conventional
      management (maintenance of glucose < 200 mg/dL) for the prevention of SSIs. No
      trials were found that evaluated strict glycaemic control in the immediate pre
      operative period or outside the setting of an intensive care unit. The trials
      were limited by small sample size, inconsistencies in the definitions of the
      outcome measures and methodological quality. Further large randomised trials are
      required to address this question and may be most appropriately performed in
      patients at high risk for SSIs.

PMID- 19588406
TI  - Cyclobenzaprine for the treatment of myofascial pain in adults.
AB  - BACKGROUND: Myofascial pain (MP) is a painful condition characterized by pain
      transmitted from trigger points (TP) within myofascial structures (in the
      muscles), local or distant from the pain. TPs can produce a characteristic
      pattern of irradiated pain or autonomic symptoms when stimulated.
      Cyclobenzaprine, a muscle relaxant that suppresses muscle spasm without
      interfering with muscle function, is used in clinical management of MP to improve
      quality of sleep and reduce pain. OBJECTIVES: To assess efficacy and safety of
      cyclobenzaprine in treating MP. SEARCH STRATEGY: The Pain Palliative and
      Supportive Care Review Group's Specialised Register, CENTRAL, PubMed, EMBASE,
      LILACS and Scielo were searched in February 2009. SELECTION CRITERIA: All RCTs
      and quasi-RCTs reporting use of cyclobenzaprine for treating MP with pain
      assessment as a primary or secondary outcome. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened studies identified, extracted data,
      assessed trial quality and analyzed results. MAIN RESULTS: We identified two
      studies with a total of 79 participants. One study, with 41 participants,
      compared cyclobenzaprine with clonazepam and with placebo. Participants taking
      cyclobenzaprine had some improvement of pain intensity compared to those on
      clonazepam, mean difference (MD) -0.25 (95% CI, -0.41 to -0.09; P value 0.002)
      and placebo, MD -0.25 (95% CI, 0.41 to -0.09; P value 0.002). The other study,
      with 38 participants, compared cyclobenzaprine with lidocaine infiltration.
      Thirty days after treatment there were statistically non-significant differences
      between comparison groups, favoring lidocaine infiltration, for the mean for
      global pain, MD 0.90 (95% CI -0.35 to 2.15, P value 0.16), and for the mean for
      pain at digital compression, MD 0.60 (95% CI -0.55 to 1.75, P value 0.30). There
      were no life-threatening adverse events associated with the medications. AUTHORS'
      CONCLUSIONS: There was insufficient evidence to support the use of
      cyclobenzaprine in the treatment of MP. We identified only two small studies in
      which a total of 35 participants were given cyclobenzaprine, and it was not
      possible to estimate risks for benefits or harms. Further high quality RCTs of
      cyclobenzaprine for treating MP need to be conducted before firm conclusions on
      its effectiveness and safety can be made. Experts in this area should elect cut
      off points for participants to identify whether a patient has achieved a
      clinically relevant reduction of pain (primary outcome), so that their results
      can be combined easily into future versions of this review.

PMID- 19588407
TI  - Electropalatography for articulation disorders associated with cleft palate.
AB  - BACKGROUND: Cleft palate is the most common congenital deformity of the face. It
      could affect speech acquisition, resulting in articulation errors that could
      persist into adulthood. Electropalatography (EPG) has been used in speech therapy
      with individuals who have articulation problems that are unresponsive to
      "standard treatment" procedures. OBJECTIVES: To determine the effectiveness of
      speech intervention using electropalatography (EPG) for treating articulation
      errors in individuals with repaired cleft palate. SEARCH STRATEGY: The following
      databases were searched: CENTRAL 2008 (Issue1), MEDLINE 1966 to March 2008,
      EMBASE 1974 to March 2008, CINAHL 1982 to March 2008, PsycINFO 1967 to March 2008
      and eight other databases. We handsearched Clinical Linguistics and Phonetics
      (1987 to 2008, Issue 2), Cleft Palate Journal/ Cleft Palate-Craniofacial Journal
      (1980 to 2008, Issue 1), and the International Journal of Language and
      Communication Disorders (1980 to 2008, Issue 1). We searched the EPG bibliography
      (Gibbon 2007). We reviewed reference lists of relevant articles and approached
      researchers to identify other possible published and unpublished studies.
      SELECTION CRITERIA: Randomised controlled studies comparing EPG intervention to
      no treatment, delayed treatment, "standard treatment", or alternative treatment
      techniques for managing articulation problems associated with cleft palate in
      children or adults. DATA COLLECTION AND ANALYSIS: One author searched the titles
      and abstracts and assessed trial quality. A second author checked judgements;
      disagreement was resolved through discussion. Three authors were available to
      examine any potential trials for possible inclusion in the review. MAIN RESULTS:
      One trial using parallel design met the inclusion criteria of this review; no
      meta-analysis was performed. The study reported that fewer therapy sessions were
      needed to achieve the treatment goals for the EPG therapy and frication display
      method (N = 2), followed by EPG therapy (N = 2) and "standard treatment" (N = 2).
      AUTHORS' CONCLUSIONS: The included trial was a small-scaled study and there were
      serious limitations in the design and methodology (e.g. allocation concealment
      was unclear, blinding of outcome assessor(s) was not ensured, few quantitative
      outcome measures were used, and the results were not reported as planned).
      Therefore, the current evidence supporting the efficacy of EPG is not strong and
      there remains a need for high-quality randomised controlled trials to be
      undertaken in this area.

PMID- 19588408
TI  - Multiple session early psychological interventions for the prevention of post
      traumatic stress disorder.
AB  - BACKGROUND: The prevention of long-term psychological distress following
      traumatic events is a major concern. Systematic reviews have suggested that
      individual Psychological Debriefing is not an effective intervention at
      preventing post traumatic stress disorder (PTSD). Recently other forms of
      intervention have been developed with the aim of preventing PTSD. OBJECTIVES: To
      examine the efficacy of multiple session early psychological interventions
      commenced within three months of a traumatic event aimed at preventing PTSD.
      Single session individual/group psychological interventions were excluded. SEARCH
      STRATEGY: Computerised databases were searched systematically, the most recent
      search was conducted in August 2008. The Journal of Traumatic Stress and the
      Journal of Consulting and Clinical Psychology were handsearched for the last two
      years. Personal communication was undertaken with key experts in the field.
      SELECTION CRITERIA: Randomised controlled trials of any multiple session early
      psychological intervention or treatment (two or more sessions) designed to
      prevent symptoms of PTSD. DATA COLLECTION AND ANALYSIS: Data were entered using
      Review Manager software. The methodological quality of included studies was
      assessed individually by two review authors. Data were analysed for summary
      effects using Review Manager 4.2. Mean difference was used for meta-analysis of
      continuous outcomes and relative risk for dichotomous outcomes. MAIN RESULTS:
      Eleven studies with a total of 941 participants were found to have evaluated
      brief psychological interventions aimed at preventing PTSD in individuals exposed
      to a specific traumatic event, examining a heterogeneous range of interventions.
      Eight studies were entered into meta-analysis. There was no observable difference
      between treatment and control conditions on primary outcome measures for these
      interventions at initial outcome (k=5, n=479; RR 0.84; 95% CI 0.60 to 1.17).
      There was a trend for increased self-report of PTSD symptoms at 3 to 6 month
      follow-up in those who received an intervention (k=4, n=292; SMD 0.23; 95% CI
      0.00 to 0.46). Two studies compared a memory structuring intervention against
      supportive listening. There was no evidence supporting the efficacy of this
      intervention. AUTHORS' CONCLUSIONS: The results suggest that no psychological
      intervention can be recommended for routine use following traumatic events and
      that multiple session interventions, like single session interventions, may have
      an adverse effect on some individuals. The clear practice implication of this is
      that, at present, multiple session interventions aimed at all individuals exposed
      to traumatic events should not be used. Further, better designed studies that
      explore new approaches to early intervention are now required.

PMID- 19588409
TI  - Oral versus intravenous steroids for treatment of relapses in multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS), a chronic inflammatory and neurodegenerative
      disease of the central nervous system (CNS), is characterized by recurrent
      relapses of CNS inflammation ranging from mild to severely disabling. Relapses
      have long been treated with steroids to reduce inflammation and hasten recovery.
      However, the commonly used intravenous methylprednisolone requires repeated
      infusions with the added costs of homecare or hospitalization, and may interfere
      with daily responsibilities. Oral steroids have been used in place of intravenous
      steroids, with lower direct and indirect costs. OBJECTIVES: The primary objective
      was to compare efficacy of oral versus intravenous steroids for MS relapses <= 6
      weeks. Secondary comparisons included subsequent relapse rate, disability,
      ambulation, hospitalization, immunological markers, radiological markers, and
      quality of life. SEARCH STRATEGY: A literature search was performed using
      Cochrane MS Group Trials Register (July 2008), Cochrane Central Register of
      Controlled Trials (CENTRAL) "The Cochrane Library 2008, issue 3, MEDLINE (PubMed)
      (1966-July 2008), EMBASE (1980-July 2008), abstracts from meetings of the
      American Academy of Neurology (2002-2008), the European Federation of
      Neurological Sciences (2002-2008), the European Committee for Treatment and
      Research in Multiple Sclerosis and American Committee for Treatment and Research
      in Multiple Sclerosis (2002-2008) handsearching. No language restrictions were
      applied. SELECTION CRITERIA: Randomized or quasi-randomized trials comparing oral
      and intravenous steroids for acute relapses (<=30 days) in clinically definite MS
      patients over age 16 were eligible. DATA COLLECTION AND ANALYSIS: Methodological
      was assessed using trial publications and personal communication. Elevant data
      was extracted, and effect size was reported as mean difference (MD),weighted mean
      difference (WMD), odds ratio (OR) and absolute risk difference (ARD). MAIN
      RESULTS: Eligible studies (167 patients) were identified. Only one outcome, the
      proportion of patients with EDSS improvement at 4 weeks, was common to three
      trials. Otherwise outcomes were too heterogeneous to pool. Only one trial
      employed an equivalence design, but all reported no statistically significant
      difference in outcomes between groups. Namely, there was no significant
      difference in the degree of recovery 4 weeks following treatment. No difference
      was found in subsequent relapse rate, disability, hospitalization, ambulation,
      bioavailability, or in magnetic resonance imaging (MRI). Due to methodological
      limitations, heterogeneous treatment regimens and limited data, formal
      conclusions about equivalence of oral and intravenous steroidscannot be made.
      Oral Megadose Corticosteroid Therapy of Acute Exacerbations of Multiple Sclerosis
      (OMEGA) trial, designed to address such limitations, is currently underway.
      AUTHORS' CONCLUSIONS: The trials reviewed support the hypothesis that no
      significant differences in clinical, radiological or pharmacological outcomes
      oral and intravenous steroids for MS relapses exist. However, with the small
      number of patients and methodological limitations, conclusions of equivalence are
      premature.

PMID- 19588410
TI  - Regular treatment with salmeterol and inhaled steroids for chronic asthma:
      serious adverse events.
AB  - BACKGROUND: Epidemiological evidence has suggested a link between beta(2)
      agonists and increased asthma mortality. There has been much debate about
      possible causal links for this association, and whether regular (daily) long
      acting beta(2)-agonists are safe. OBJECTIVES: The aim of this review is to assess
      the risk of fatal and non-fatal serious adverse events in trials that randomised
      patients with chronic asthma to regular salmeterol with inhaled corticosteroids
      versus the same dose of inhaled corticosteroids alone. SEARCH STRATEGY: Trials
      were identified using the Cochrane Airways Group Specialised Register of trials.
      Web sites of clinical trial registers were checked for unpublished trial data and
      Food and Drug Administration (FDA) submissions in relation to salmeterol were
      also checked. The date of the most recent search was October 2008. SELECTION
      CRITERIA: Controlled parallel design clinical trials on patients of any age and
      severity of asthma were included if they randomised patients to treatment with
      regular salmeterol and inhaled corticosteroids (in separate or combined
      inhalers), and were of at least 12 weeks duration. DATA COLLECTION AND ANALYSIS:
      Two authors independently selected trials for inclusion in the review. Outcome
      data were independently extracted by two authors. Unpublished data on mortality
      and serious adverse events were obtained from the sponsors, and from FDA
      submissions. MAIN RESULTS: The review included 30 studies (10,873 participants)
      in adults and adolescents, and three studies (1,173 participants) in children.
      The overall risk of bias was low and data on serious adverse events were obtained
      from all studies.Six deaths occurred in 5,710 adults on regular salmeterol with
      inhaled corticosteroids, and five deaths in 5,163 adults on regular inhaled
      corticosteroids at the same dose. The difference was not statistically
      significant (Peto OR 1.05; 95% CI 0.32 to 3.47) and the absolute difference
      between groups in risk of death of any cause was 0.00005 (95% CI -0.002 to
      0.002). No deaths were reported in 1,173 children, and no deaths were reported to
      be asthma-related.Non-fatal serious adverse events of any cause were reported in
      134 adults on regular salmeterol with inhaled corticosteroids, compared to 103
      adults on regular inhaled corticosteroids; again this was not a significant
      increase (Peto OR 1.17; 95% CI 0.90 to 1.52). The absolute difference in the risk
      of non-fatal serious adverse events was 0.003 (95% CI -0.002 to 0.009).There were
      three of 586 children with serious adverse events on regular salmeterol with
      inhaled corticosteroids, compared to four out of 587 on regular inhaled
      corticosteroids: there was no significant difference between treatments (Peto OR
      0.75; 95% CI 0.17 to 3.31).Asthma-related serious adverse events were reported in
      23 and 21 adults in each group respectively, a non-significant difference (Peto
      OR 0.95; 95% CI 0.52 to 1.73), and only one event was reported in children.
      AUTHORS' CONCLUSIONS: No significant differences have been found in fatal or non
      fatal serious adverse events in trials in which regular salmeterol has been
      randomly allocated with inhaled corticosteroids, in comparison to inhaled
      corticosteroids at the same dose. Although 10,873 adults and 1,173 children have
      been included in trials, the number of patients suffering adverse events is too
      small, and the results are too imprecise to confidently rule out a relative
      increase in all-cause mortality or non-fatal adverse events. It is therefore not
      possible to determine whether the increase in all-cause non-fatal serious adverse
      events reported in the previous meta-analysis on regular salmeterol alone is
      abolished by the additional use of regular inhaled corticosteroids. The absolute
      difference between groups in the risk of serious adverse events was small. There
      were no asthma-related deaths and few asthma-related serious adverse events.
      Clinical decisions and information for patients regarding regular use of
      salmeterol have to take into account the balance between known symptomatic
      benefits of salmeterol and the degree of uncertainty and concern associated with
      its potential harmful effects.

PMID- 19588411
TI  - Statins for age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a progressive late onset
      disorder of the macula affecting central vision. Age-related macular degeneration
      is the leading cause of blindness in people over 65 years in industrialized
      countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence
      has shown AMD shares a number of risk factors with atherosclerosis, leading to
      the hypothesis that statins may exert protective effects in AMD. OBJECTIVES: To
      examine the effectiveness of statins compared with other treatments, no
      treatment, or placebo in delaying the onset and/or progression of AMD. SEARCH
      STRATEGY: We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE and LILACS
      on 30 April 2009 and the WHO International Clinical Trials Registry Platform on
      11 May 2009. We searched reference lists and the Science Citation Index. There
      were no language or date restrictions in the search for trials. SELECTION
      CRITERIA: We included randomized controlled trials (RCTs) that compared statins
      with other treatments, no treatment, or placebo in participants who were either
      susceptible to or diagnosed as having early stages of AMD. DATA COLLECTION AND
      ANALYSIS: Two authors independently evaluated the search results against the
      selection criteria. Two Italian speaking colleagues extracted data. One author
      entered data. We did not perform a meta-analysis because only one completed RCT
      was identified. MAIN RESULTS: Two studies met the selection criteria. One trial
      reported insufficient details to assess the risk of bias; the other trial is
      ongoing.Of the completed trial, the analyses of 30 participants did not show a
      statistically significant difference between the simvastatin and the placebo arm
      in visual acuity at three months of treatment (decimal visual acuity 0.21+/- 0.56
      in simvastatin and 0.19+/- 0.40 in placebo arm) or 45 days after the completion
      of treatment (decimal visual acuity 0.20+/- 0.50 in simvastatin and 0.19+/- 0.48
      in placebo arm). The lens and retina status were unchanged during and after the
      treatment period for both groups.Of the ongoing trial, the preliminary analyses
      of 42 participants who completed 12 months follow-up did not show a statistically
      significant difference between the simvastatin and the placebo arm in visual
      acuity, drusen score or visual function (effect estimates and confidence
      intervals were not available). We contacted the investigators and will update the
      review as data become available. AUTHORS' CONCLUSIONS: Evidence from currently
      available RCTs was insufficient to conclude that statins have any role in
      preventing or delaying the onset or progression of AMD.

PMID- 19588412
TI  - Interventions for erythema nodosum leprosum.
AB  - BACKGROUND: Erythema nodosum leprosum (ENL) is a serious immunological
      complication of leprosy, causing inflammation of skin, nerves, other organs, and
      general malaise. Many different therapies exist for ENL, but it is unclear if
      they work or which therapy is optimal. OBJECTIVES: To assess the effects of
      interventions for erythema nodosum leprosum. SEARCH STRATEGY: We searched the
      Cochrane Skin Group Specialised Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2009), MEDLINE
      (from 2003), EMBASE (from 2005), LILACS and AMED (from inception), CINAHL (from
      1981), and databases of ongoing trials, all in March 2009. We checked reference
      lists of articles and contacted the American Leprosy Missions in Brazil to locate
      studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of interventions
      for ENL in people with leprosy. DATA COLLECTION AND ANALYSIS: Two authors
      performed study selection, assessed trial quality, and extracted data. MAIN
      RESULTS: We included 13 studies with a total of 445 participants. The quality of
      the trials was generally poor and no results could be pooled due to the
      treatments being so heterogeneous. Treatment with thalidomide showed a
      significant remission of skin lesions compared to acetylsalicylic acid (aspirin)
      (RR 2.43; 95% CI 1.28 to 4.59) (1 trial, 92 participants). Clofazimine treatment
      was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 1.36 to
      9.91) (1 trial, 24 participants), and thalidomide (fewer recurrences; RR 0.08;
      95% CI 0.01 to 0.56) (1 trial, 72 participants). We did not find any significant
      benefit for intravenous betamethasone compared to dextrose (1 trial, 10
      participants), pentoxifylline compared to thalidomide (1 trial, 44 participants),
      indomethacin compared to prednisolone, aspirin or chloroquine treatments (2
      trials, 80 participants), or levamisole compared to placebo (1 trial, 12
      participants). Mild to moderate adverse events were significantly lower in
      participants taking 100 mg thalidomide compared to 300 mg thalidomide daily (RR
      0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported
      in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI
      1.10 to 3.35). None of the studies assessed quality of life or economic outcomes.
      AUTHORS' CONCLUSIONS: There is some evidence of benefit for thalidomide and
      clofazimine, but generally we did not find clear evidence of benefit for
      interventions in the management of ENL. However, this does not mean they do not
      work, because the studies were small and poorly reported. Larger studies using
      clearly defined participants, outcome measures, and internationally recognised
      scales are urgently required.

PMID- 19588413
TI  - Local anaesthetic wound infiltration and abdominal nerves block during caesarean
      section for postoperative pain relief.
AB  - BACKGROUND: Caesarean section delivery is becoming more frequent. Childbirth is
      an emotion-filled event and the mother needs to bond with her newborn baby as
      early as possible. Any intervention that leads to improvement in pain relief is
      worthy of investigation. Local anaesthetics, either on their own or in
      combination with opioids or nonsteroidal antiinflammatory drugs, have been
      employed as an adjunct to other postoperative pain relief strategies. Conflicting
      reports were noted. OBJECTIVES: To assess the effects of local anaesthetic agent
      wound infiltration/irrIgation and/or abdominal nerve blocks on post-caesarean
      section pain and the mother's well being and interaction with her baby. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (April 2009). SELECTION CRITERIA: Randomised controlled trials of pre
      emptive local analgesia during caesarean section. DATA COLLECTION AND ANALYSIS:
      One author extracted data. The second author checked the data. MAIN RESULTS:
      Twenty studies (1150 women) were included. Women who had caesarean section
      performed under regional analgesia and had wound infiltration had a decrease in
      morphine consumption at 24 hours (SMD -1.70mg; 95% confidence interval (CI) -2.75
      to -0.94) compared to placebo.In women under general anaesthesia, with caesarean
      section wound infiltration and peritoneal spraying with local anaesthetic (one
      study, 100 participants), the need for opioid rescue was reduced (risk ratio (RR)
      0.51; 95% CI 0.38 to 0.69). The numerical pain score (0 to10) within the first
      hour was also reduced (mean difference (MD) -1.46; 95% CI -2.60 to -0.32).Women
      with regional analgesia who had local anaesthetic and non-steriodal anti
      inflammatory cocktail wound infiltration consumed less morphine (one study, 60
      participants; MD -7.40 mg; 95% CI -9.58 to -5.22) compared to local anaesthetic
      control.Women who had regional analgesia with abdominal nerves blocked had
      decreased opioid consumption (four studies, 175 participants; MD -25.80 mg; 95%
      CI -50.39 to -5.37).For the outcome of visual analogue scale 0 to 10 over 24
      hours, no advantage was demonstrated in the single study of 50 participants who
      had wound infiltrated with a mixture of local analgesia and narcotics versus
      local analgesia.Addition of ketamine to the local analgesia in women who had
      regional analgesia does not confer any advantage. AUTHORS' CONCLUSIONS: Local
      analgesia infiltration and abdominal nerve blocks as adjuncts to regional
      analgesia and general anaesthesia are of benefit in caesarean section by reducing
      opioid consumption. Nonsteroidal anti-inflammatory drugs as an adjuvant may
      confer additional pain relief.

PMID- 19588414
TI  - Treatment for idiopathic and hereditary neuralgic amyotrophy (brachial neuritis).
AB  - BACKGROUND: Neuralgic amyotrophy (also know as Parsonage-Turner syndrome or
      brachial plexus neuritis) is a distinct peripheral nervous system disorder
      characterised by episodes (attacks) of extreme neuropathic pain and rapid
      multifocal weakness and atrophy in the upper limbs. Neuralgic amyotrophy has both
      an idiopathic and hereditary form, with similar clinical symptoms but generally
      an earlier age of onset and more episodes in the hereditary form. The current
      hypothesis is that the episodes are caused by an immune-mediated response to the
      brachial plexus. Recovery is slow, in months to years, and many patients are left
      with residual pain and decreased exercise tolerance of the affected limb(s).
      Anecdotal evidence suggests that corticosteroids may relieve pain or help improve
      functional recovery. OBJECTIVES: The objective was to provide a systematic review
      of all randomised clinical trials of treatment in neuralgic amyotrophy. SEARCH
      STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register
      (April 2 2009), MEDLINE (January 1966 to April 2 2009), EMBASE (January 1980 to
      April 2 2009), CINAHL (January 1982 to April 2 2009), and LILACS (January 1982 to
      April 2 2009) for randomised controlled trials of treatment for neuralgic
      amyotrophy. SELECTION CRITERIA: Any randomised or quasi-randomised trial of any
      intervention for neuralgic amyotrophy would be included in the review. DATA
      COLLECTION AND ANALYSIS: Two review authors extracted the data (RH, NvA) and two
      authors assessed study quality and performed data extraction independently (NvA,
      BvE). MAIN RESULTS: No randomised or quasi-randomised trials were identified. In
      30 articles anecdotal evidence was found on treatment for neuralgic amyotrophy.
      Only three of these articles contained more than 10 treated cases, with one
      providing sufficient details to calculate the primary and secondary outcome
      measures for this review. AUTHORS' CONCLUSIONS: At this moment there is no
      evidence from randomised trials on any form of treatment for neuralgic
      amyotrophy. Evidence from one open-label retrospective series suggests that oral
      prednisone given in the first month after onset can shorten the duration of the
      initial pain and leads to earlier recovery in some patients. Randomised clinical
      trials are needed to establish the efficacy of treatment with corticosteroids or
      other immune-modulating therapies.

PMID- 19588415
TI  - Aldosterone antagonists for preventing the progression of chronic kidney disease.
AB  - BACKGROUND: Treatment with angiotensin converting enzyme inhibitors (ACEi) and
      angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria
      and retard the progression of chronic kidney disease (CKD). But some patients do
      not attain complete resolution of proteinuria and might have higher aldosterone
      levels within few months of treatment. The addition of aldosterone antagonists
      may be beneficial to these patients for reduction of progression of renal damage.
      OBJECTIVES: We evaluated the benefits and harms of adding aldosterone antagonists
      in patients with CKD currently treated with ACEi and/or ARB. SEARCH STRATEGY: We
      searched MEDLINE, EMBASE, CENTRAL, and hand-searched reference lists of
      textbooks, articles and scientific proceedings for relevant articles. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing
      aldosterone antagonists in addition to ACEi and/or ARB versus ACEi and/or ARB
      alone were included. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed study quality and extracted data. Statistical analyses were performed
      using a random effects model and heterogeneity was tested formally using the
      Cochran Q and I(2) statistic. Results were expressed as mean difference (MD) for
      continuous outcomes and risk ratio (RR) for dichotomous outcomes with 95%
      confidence intervals (CI). MAIN RESULTS: Ten studies (845 patients) were
      included. Compared to ACEi and/or ARB plus placebo, non-selective aldosterone
      antagonists along with ACEi and/or ARB significantly reduced 24 hour proteinuria
      (7 studies, 372 patients; MD -0.80 g, 95% CI -1.23 to -0.38). There was a
      significant reduction in both systolic and diastolic blood pressure at the end of
      treatment with the addition of non-selective aldosterone antagonists to ACEi
      and/or ARB. This did not translate into an improvement in glomerular filtration
      rate (5 studies, 306 patients; MD -0.70 mL/min/1.73 m(2), 95% CI -4.73 to 3.34).
      There was a significant increase in the risk of hyperkalaemia with the addition
      of non-selective aldosterone antagonists to ACEi and/or ARB (8 studies, 436
      patients; RR 3.06, 95% CI 1.26 to 7.41). In two studies, the addition of
      selective aldosterone antagonists to ACEi resulted in an additional reduction in
      24 hour proteinuria but without any impact on BP and renal function. Data on
      cardiovascular outcomes, long-term renal outcomes and mortality were not
      available. AUTHORS' CONCLUSIONS: Aldosterone antagonists contribute to reduction
      of proteinuria in patients with CKD who are already on ACEi and ARB but increase
      the risk of hyperkalaemia. Available studies are small and have short follow-up.
      Long-term effects on renal outcomes, mortality and safety are unknown.

PMID- 19588416
TI  - Interventions for post-stroke fatigue.
AB  - BACKGROUND: Fatigue after stroke is common and distressing to patients. The best
      way to treat this fatigue is uncertain. Theoretically, several different
      interventions may be of benefit. OBJECTIVES: To determine whether any treatment
      for fatigue after stroke reduces the proportion of patients with fatigue, or
      fatigue severity, or both, and to determine the effect of treatment on health
      related quality of life, disability, dependency and death, and whether such
      treatments are cost effective. SEARCH STRATEGY: We searched the Cochrane Stroke
      Group Trials Register (last searched January 2008), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (1950 to
      February 2008), EMBASE (1980 to February 2008), CINAHL (1982 to February 2008),
      AMED (1985 to February 2008), PsycINFO (1967 to February 2008), Digital
      Dissertations (1861 to March 2008), PsycBITE (searched March 2008), PEDro
      (searched March 2008), and British Nursing Index (1985 to March 2008). We also
      searched four trials registries, scanned reference lists, performed citation
      tracking of included trials, and contacted experts. SELECTION CRITERIA: The
      review author who performed the searches scrutinised all titles and abstracts,
      excluded irrelevant references, and obtained references for potentially relevant
      studies. A second review author independently scrutinised potentially relevant
      studies to determine whether they fulfilled inclusion criteria. We included
      randomised controlled trials of any intervention in patients with stroke where
      fatigue was a primary or secondary endpoint. DATA COLLECTION AND ANALYSIS: The
      two review authors who scrutinised references independently extracted data. We
      performed a narrative review; we had intended to perform a meta-analysis but this
      was not possible as the interventions were too diverse for data to be combined.
      MAIN RESULTS: We identified three trials. One randomised 83 patients with
      emotional disturbance after stroke to fluoxetine or placebo. After correcting for
      differences in fatigue severity at baseline, there was no significant difference
      in fatigue between groups at follow up. The second trial randomised 31 women with
      subarachnoid haemorrhage to tirilazad or placebo, of whom 18 were available for
      follow up. There was no difference in fatigue between the two groups. The third
      trial investigated a chronic disease self-management programme in 1150 patients
      with chronic diseases, of whom 125 had had a stroke. There was no difference in
      fatigue at follow up between the treatment and control in the subgroup with
      stroke. AUTHORS' CONCLUSIONS: There is insufficient evidence available to guide
      the management of fatigue after stroke. Further trials are required.

PMID- 19588417
TI  - Acanthopanax for acute ischaemic stroke.
AB  - BACKGROUND: Acute ischaemic stroke is a common cause of death and disability. A
      number of studies published in China have shown that acanthopanax is beneficial
      for acute ischaemic stroke. OBJECTIVES: To assess the efficacy and safety of
      acanthopanax in patients with acute ischaemic stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched January 2008),
      the Chinese Stroke Trials Register (last searched March 2008), and the Trials
      Register of the Cochrane Complementary Medicine Field (last searched January
      2008). In addition, we searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1966 to March
      2008), EMBASE (1980 to March 2008), CINAHL (1982 to March 2008), AMED (1985 to
      March 2008), and nine Chinese databases, including the China Biological Medicine
      Database (CBM-disc) (1979 to March 2008). We handsearched three Chinese journals
      and searched reference lists, relevant clinical trials registers and research
      databases. In an attempt to identify further published, unpublished, and ongoing
      trials, we contacted a pharmaceutical company, researchers and study authors.
      SELECTION CRITERIA: We included randomised controlled trials comparing
      acanthopanax with placebo or open control (no placebo) in patients with acute
      ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors selected
      trials for inclusion, assessed trial quality and extracted the data
      independently. MAIN RESULTS: We included 13 trials (962 participants); the period
      of follow up in all included trials ranged from 10 to 30 days. None of the trials
      reported the pre-specified primary outcome death or dependency during the follow
      up period. The outcome measure in all included trials was the improvement of
      neurological deficit after treatment; acanthopanax was associated with a
      significant increase in the number of participants whose neurological impairment
      improved (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.15 to 1.29). Two
      trials reported adverse events; five trials reported no adverse events. AUTHORS'
      CONCLUSIONS: The risk of bias in all the included trials was high, and hence the
      data were not adequate to draw reliable conclusions about the efficacy of
      acanthopanax in acute stroke. Much larger trials of greater methodological
      quality are needed.

PMID- 19588418
TI  - Intravenous immunoglobulin as adjuvant therapy for Wegener's granulomatosis.
AB  - BACKGROUND: Wegener's granulomatosis (WG) is a necrotizing small-vessel
      vasculitis that can affect any organ in the body but mainly affects the upper and
      lower respiratory tract, the kidneys, joints, skin and eyes. The current mainstay
      of remission induction therapy is systemic corticosteroids in combination with
      oral daily cyclophosphamide (CYC) which induces remission in 75% to 100% of
      cases. Although standard therapy is effective in inducing partial or complete
      remission, 50% of complete remissions are followed by at least one relapse.
      OBJECTIVES: To determine if intravenous immunoglobulin (IVIg) adjuvant therapy
      provides a therapeutic advantage over and above treatment with systemic
      corticosteroids in combination with immunosuppressants for the treatment of WG.
      SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched
      their Trials Register (last searched 8 May) and the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue
      2). We searched MEDLINE (1966 to May 2009) and EMBASE (1980 to May 2009).
      SELECTION CRITERIA: Randomized controlled trials (RCTs), or quasi RCTs, or
      randomized cross-over trials. Participants had to be adults with a confirmed
      diagnosis of WG. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data and assessed trial quality. Relative risk was used to analyze
      dichotomous variables, and mean difference (MD) was used to analyze continuous
      variables. MAIN RESULTS: We included one RCT with 34 participants who were
      randomly assigned to receive IVIg or placebo once daily in addition to
      azathioprine and prednisolone for remission maintenance. There were no
      significant differences between adjuvant IVIg and adjuvant placebo in mortality,
      serious adverse events, time to relapse, open-label rescue therapy, and infection
      rates. The fall in disease activity score, derived from patient-reported
      symptoms, was slightly greater in the IVIg group than in the placebo group at one
      month (MD 2.30; 95% Confidence interval (CI) 1.12 to 3.48, P < 0.01) and three
      months (MD 1.80; 95% CI 0.35 to 3.25, P = 0.01). There was a significant increase
      in total adverse events in the IVIg group (relative risk (RR) 3.50; 95% CI 1.44
      to 8.48, P < 0.01). AUTHORS' CONCLUSIONS: There is insufficient evidence from one
      RCT that IVIg adjuvant therapy provides a therapeutic advantage compared with the
      combination of steroids and immunosuppressants for patients with WG. Given the
      high cost of IVIg (one dose at 2g/kg for a 70kg patient = $8,400), it should be
      limited to treat WG in the context of a well conducted RCT powered to detect
      patient-relevant outcomes.

PMID- 19588419
TI  - Pregabalin for acute and chronic pain in adults.
AB  - BACKGROUND: Antiepileptic drugs have been used in pain management since the
      1960s. Pregabalin is a recently developed antiepileptic drug also used in
      management of chronic neuropathic pain conditions. OBJECTIVES: To assess
      analgesic efficacy and associated adverse events of pregabalin in acute and
      chronic pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and CENTRAL to May
      2009 for randomised controlled trials (RCTs). Additional studies were identified
      from the reference lists of retrieved papers and on-line clinical trial
      databases. SELECTION CRITERIA: Randomised, double blind trials reporting on the
      analgesic effect of pregabalin, with subjective pain assessment by the patient as
      either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Two
      independent review authors extracted data and assessed trial quality. Numbers
      needed-to-treat-to-benefit (NNTs) were calculated, where possible, from
      dichotomous data for effectiveness, adverse events and study withdrawals. MAIN
      RESULTS: There was no clear evidence of beneficial effects of pregabalin in
      established acute postoperative pain. No studies evaluated pregabalin in chronic
      nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600
      mg daily was effective in patients with postherpetic neuralgia, painful diabetic
      neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003
      participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was
      demonstrated for dichotomous outcomes equating to moderate or substantial pain
      relief, alongside lower rates for lack of efficacy discontinuations with
      increasing dose. The best (lowest) NNT for each condition for at least 50% pain
      relief over baseline (substantial benefit) for 600 mg pregabalin daily compared
      with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic
      neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for
      central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg
      pregabalin daily somnolence typically occurred in 15% to 25% and dizziness
      occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to
      28%. The proportion of participants reporting at least one adverse event was not
      affected by dose, nor was the number with a serious adverse event, which was not
      more than with placebo.Higher rates of substantial benefit were found in
      postherpetic neuralgia and painful diabetic neuropathy than in central
      neuropathic pain and fibromyalgia. For moderate and substantial benefit on any
      outcome NNTs for the former were generally six and below for 300 mg and 600 mg
      daily; for fibromyalgia NNTs were much higher, and generally seven and above.
      AUTHORS' CONCLUSIONS: Pregabalin has proven efficacy in neuropathic pain
      conditions and fibromyalgia. A minority of patients will have substantial benefit
      with pregabalin, and more will have moderate benefit. Many will have no or
      trivial benefit, or will discontinue because of adverse events. Individualisation
      of treatment is needed to maximise pain relief and minimise adverse events. There
      is no evidence to support the use of pregabalin in acute pain scenarios.

PMID- 19588420
TI  - Treatment of seizures in multiple sclerosis.
AB  - BACKGROUND: Epileptic seizures occur in only a minority of patients with multiple
      sclerosis (MS), but can have serious consequences. The available literature
      suggests an association of seizures in MS with cortical and subcortical
      demyelinating lesions, which suggest that seizures in MS are probably most often
      symptomatic rather that idiopathic. It is currently unknown whether patients with
      MS should be treated differently from other patients with epileptic seizures.
      OBJECTIVES: To evaluate the efficacy and safety of antiepileptic treatments in
      patients with MS. SEARCH STRATEGY: We searched for double-blind, single-blind or
      unblinded randomised controlled trials on antiepileptic treatment in patients
      with MS through electronic searches of The Cochrane Multiple Sclerosis Group's
      and Cochrane Epilepsy Group's Trials Registers, Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE (From 1966 - Jan
      2008) and EMBASE (From 1974 - Jan 2008). SELECTION CRITERIA: Double-blind, single
      blind or unblinded randomised controlled trials on antiepileptic treatment in
      patients with MS. DATA COLLECTION AND ANALYSIS: Searches yielded a total of 379
      citations (CENTRAL: 20, MEDLINE: 264, EMBASE: 95). We perused titles and
      abstracts for relevance and independently excluded all 379 citations as clearly
      not meeting the inclusion criteria. MAIN RESULTS: We found no studies meeting our
      inclusion criteria. AUTHORS' CONCLUSIONS: Well-designed randomised controlled
      trials are needed to guide clinical practice. Such trials should preferably
      contain a head-to-head comparison of antiepileptic drugs in patients with MS.

PMID- 19588421
TI  - Cervical assessment by ultrasound for preventing preterm delivery.
AB  - BACKGROUND: Measurement of cervical length (CL) by transvaginal ultrasound (TVU)
      is predictive of preterm birth (PTB). It is unclear if this screening test is
      effective for prevention of PTB. OBJECTIVES: To assess the effectiveness of
      antenatal management based on TVU CL screening for preventing PTB. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (September 2008), MEDLINE (1966 to September 2008), and reviewed the
      reference list of all articles. SELECTION CRITERIA: Published and unpublished
      randomized controlled trials including pregnant women between the gestational
      ages of 14 to 32 weeks screened with TVU CL for risk of PTB. This review focuses
      exclusively on studies based on knowledge versus no knowledge of TVU CL results.
      DATA COLLECTION AND ANALYSIS: All potential studies identified as in the search
      were assessed for inclusion by three independent review authors. We also analyzed
      studies for quality measures and extracted data. MAIN RESULTS: Of 12 trials
      identified, five were eligible for inclusion (n = 507). Three included singleton
      gestations with preterm labor (PTL); one included singleton gestations with
      preterm prelabour rupture of membranes (PPROM); and one included twin gestations
      without or with PTL.In the three trials of singleton gestations with PTL, 290
      women were randomized; 147 to knowledge and 143 to no knowledge of TVU CL.
      Knowledge of TVU CL results was associated with a non-significant decrease in PTB
      at less than 37 weeks (22.3% versus 34.7%, respectively; risk ratio 0.59, 95%
      confidence interval (CI) 0.26 to 1.32). Delivery occurred at a later gestational
      age in the knowledge versus no knowlege groups (mean difference 0.64 weeks (CI
      0.03 to 1.25)). All other outcomes for which there were available data (PTB at
      less than 34 or 28 weeks; birthweight less than 2500 grams; perinatal death;
      maternal hospitalization; tocolysis; and steroids for fetal lung maturity) were
      similar in the two groups.The trial of singleton gestations with PPROM (n = 92)
      evaluated as its primary outcome safety of TVU CL in this population, and not its
      effect on management. The incidence of maternal and neonatal infections was
      similar in the TVU CL and no TVU CL groups.In the trial of twin gestations with
      or without PTL (n = 125), PTB at less than 36, 34, or 30 weeks, gestational age
      at delivery, and other perinatal and maternal outcomes were similar in the TVU CL
      and the no TVU CL groups. Life table analysis revealed significantly less preterm
      birth at less than 35 weeks in the TVU CL group compared to the no TVU CL group
      (P = 0.02). AUTHORS' CONCLUSIONS: Currently there is insufficient evidence to
      recommend routine screening of asymptomatic or symptomatic pregnant women with
      TVU CL. Since there is a non-significant association between knowledge of TVU CL
      results and a lower incidence of PTB at less than 37 weeks in symptomatic women,
      we encourage further research. Future studies should look at specific populations
      separately (eg singleton versus twins; symptoms of PTL or no such symptoms),
      report on all pertinent maternal and perinatal outcomes, and include cost
      effectiveness analyses. Most importantly, future studies should include a clear
      protocol for management of women based on TVU CL results, so that it can be
      easily evaluated and replicated.

PMID- 19588422
TI  - Therapeutic drug monitoring of antiretrovirals for people with HIV.
AB  - BACKGROUND: Despite the efficacy of combination antiretroviral therapy (ART) and
      the improvement in prognosis of those living with HIV/AIDS, a large proportion of
      individuals on ART does not achieve or maintain adequate virological suppression.
      Several tools have been proposed to enhance ART outcomes, including therapeutic
      drug monitoring (TDM) of antiretrovirals (ARVs). The aim of ARV TDM is to
      identify elevated (potentially toxic) or low (potentially sub-therapeutic) ARV
      concentrations. ARV TDM may thus optimise efficacy and minimise toxicity of ART.
      OBJECTIVES: To evaluate whether ARV TDM reduces mortality and morbidity of adult
      patients on ART. The primary outcome measures that have been assessed include
      death (all cause); occurrence of HIV-related events (death or AIDS-defining
      illness) and the proportion of patients achieving and maintaining an undetectable
      viral load, as defined by the authors. SEARCH STRATEGY: We conducted a
      comprehensive search including both published and unpublished studies in all
      languages in MEDLINE, EMBASE and The Cochrane Library, between January 1980 and
      January 2008. Databases listing conference abstracts and reference lists of
      articles were searched. Additional data were sought from relevant authors;
      however, no additional data were provided. SELECTION CRITERIA: Only randomized
      controlled trials conducted subsequent to the introduction of combination ART
      were included in this systematic review. Participants could be on either a
      protease inhibitor (PI)-based regimen or non-nucleoside reverse transcriptase
      (NNRTI)-based regimen and be either ARV-naive or -experienced. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently assessed and extracted data for
      analysis. Meta-analysis was conducted where appropriate. Where study outcomes
      could not be combined, a narrative review was performed. Outcome measures for
      dichotomous data were reported as a relative risk with 95% confidence intervals.
      Stratified analyses were conducted by ARV regimen and treatment groups.
      Heterogeneity between studies was anticipated; therefore, random effects models
      were chosen to generate pooled effects. Differences in the findings were assessed
      by the chi square test for heterogeneity (p <0.1) that was quantified by the
      Higgins I(2) statistic. MAIN RESULTS: Identified were 1408 records, and eight
      trials with a total of 1181 participants were included in the review. Trials were
      conducted in higher income earning countries between 2002 and 2007. Sample sizes
      ranged between 40 and 230. The methodological quality of the studies was judged
      to be generally good, although allocation concealment was reported in only three
      of the eight studies. A meta-analysis including three studies did not show any
      significant effect on virological suppression below 500 HIV-RNA copies/mL at one
      year (RR 1.28; [0.86, 1.92] chi(2) = 11.55 (P = 0.003), I(2) = 83%). Two trials
      including participants predominantly treated with unboosted PI-based regimens
      reported a 49% increased likelihood of achieving a HIV-RNA viral load below 500
      copies/mL at 52 weeks (RR 1.49 [1.20, 1.83] chi(2) = 0.69 (P = 0.4), I(2) = 0%).
      Safety outcomes were reported in four studies and were similar between TDM and
      standard of care. Uptake of expert advice based on TDM results was good in two
      trials (>70%), but low (<35%) in the remaining three studies that reported uptake
      of the recommendations. AUTHORS' CONCLUSIONS: Our review does not support routine
      use of ARV TDM in ARV-naive or -experienced patients on either boosted PI or
      NNRTI ART regimens. TDM in treatment-naive participants on a PI-based ART
      regimen, particularly if unboosted by ritonavir, may improve virological
      outcomes. Trials were underpowered with small sample sizes, short durations of
      follow-up and generally poor uptake of TDM recommendations. As these trials were
      conducted in higher income earning countries, results may not be generalisable to
      resource-limited countries where the burden of HIV is heaviest.

PMID- 19588423
TI  - Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on
      individual patient data.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer
      patients and may improve quality of life, but there are concerns that ESAs might
      increase mortality. OBJECTIVES: Our objectives were to examine the effect of ESAs
      and identify factors that modify the effects of ESAs on overall survival,
      progression free survival, thromboembolic and cardiovascular events as well as
      need for transfusions and other important safety and efficacy outcomes in cancer
      patients. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Embase and
      conference proceedings for eligible trials. Manufacturers of ESAs were contacted
      to identify additional trials. SELECTION CRITERIA: We included randomized
      controlled trials comparing epoetin or darbepoetin plus red blood cell
      transfusions (as necessary) versus red blood cell transfusions (as necessary)
      alone, to prevent or treat anemia in adult or pediatric cancer patients with or
      without concurrent antineoplastic therapy. DATA COLLECTION AND ANALYSIS: We
      performed a meta-analysis of randomized controlled trials comparing epoetin
      alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus
      transfusion alone, for prophylaxis or therapy of anemia while or after receiving
      anti-cancer treatment. Patient-level data were obtained and analyzed by
      independent statisticians at two academic departments, using fixed-effects and
      random-effects meta-analysis. Analyses were according to the intention-to-treat
      principle. Primary endpoints were on study mortality and overall survival during
      the longest available follow-up, regardless of anticancer treatment, and in
      patients receiving chemotherapy. Tests for interactions were used to identify
      differences in effects of ESAs on mortality across pre-specified subgroups. The
      present review reports only the results for the primary endpoint. MAIN RESULTS: A
      total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died
      on-study and 4993 overall. ESAs increased on study mortality (combined hazard
      ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95%
      CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2)
      7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients
      receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98
      1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence
      for a difference between trials of patients receiving different cancer treatments
      (P for interaction=0.42). AUTHORS' CONCLUSIONS: ESA treatment in cancer patients
      increased on study mortality and worsened overall survival. For patients
      undergoing chemotherapy the increase was less pronounced, but an adverse effect
      could not be excluded.

PMID- 19588424
TI  - Antibiotic prophylaxis for leptospirosis.
AB  - BACKGROUND: Leptospira infection is a global zoonosis with significant health
      impact for agricultural workers and those persons whose work or recreation takes
      them into endemic areas. OBJECTIVES: This systematic review assessed the current
      literature for evidence for or against use of antibiotic prophylaxis against
      Leptospira infection (leptospirosis). SEARCH STRATEGY: The authors searched The
      Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE,
      and SCI-Expanded as well as relevant professional society meeting abstracts until
      January 2009. SELECTION CRITERIA: Prospective, randomised clinical trials
      studying antibiotic prophylaxis against leptospirosis were selected. DATA
      COLLECTION AND ANALYSIS: Data collection abstracted participant demographics and
      outcomes as well as features of trial design and quality. Trial results were
      analysed to independently determine outcomes, while multiple trial data was
      pooled when relevant. MAIN RESULTS: Three trials were included, all of which
      evaluated doxycyline use. Trial quality suffered from a lack of intention-to
      treat analysis and variability across trials in methodology and targeted
      outcomes. One trial assessed post-exposure prophylaxis in an indigenous
      population after a flood without apparent efficacy in reduction of clinical or
      laboratory identified Leptospira infection. Two trials assessed pre-exposure
      prophylaxis, one among deployed soldiers and another in an indigenous population.
      Despite an odds ratio of 0.05 (95% CI 0.01 to 0.36) for laboratory-identified
      infection among deployed soldiers on doxycyline in one of these two trials,
      pooled data showed no statistically significant reduction in Leptospira infection
      among participants (Odds ratio 0.28 (95% CI 0.01 to 7.48). Minor adverse events
      (predominantly nausea and vomiting) were more common among those on doxycycline
      with an odds ratio of 11 (95% CI 2.1 to 60). AUTHORS' CONCLUSIONS: Regular use of
      weekly oral doxycycline 200 mg increases the odds for nausea and vomiting with
      unclear benefit in reducing Leptospira seroconversion or clinical consequences of
      infection.

PMID- 19588425
TI  - Safety of topical corticosteroids in pregnancy.
AB  - BACKGROUND: Topical corticosteroids are the most frequently prescribed
      dermatological treatment and are frequently used by pregnant women with skin
      conditions. However, little is known about their safety in pregnancy. OBJECTIVES:
      To assess the effects of topical corticosteroids on pregnancy outcomes. SEARCH
      STRATEGY: On 5th May 2009 we searched the Cochrane Skin Group Specialised
      Register, the Cochrane Pregnancy and Childbirth Group Specialised Register,
      CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (from 2003), and EMBASE
      (from 2005). We searched LILACS, CINAHL, British Nursing Index, SCI-EXPANDED,
      BIOSIS Previews, Conference Papers Index, and Conference Proceedings Citation
      Index-Science from inception to May 2009. We scanned the bibliographies of the
      included studies, published reviews, and articles that had cited the included
      studies. Pharmaceutical companies that have introduced an original topical
      corticosteroid product were contacted. SELECTION CRITERIA: Randomised controlled
      trials and cohort studies of topical corticosteroids in pregnant women, and case
      control studies comparing maternal exposure to topical corticosteroids between
      cases and controls were included where outcomes were those we had pre-specified.
      Outcomes included mode of delivery, congenital abnormality, birthweight, preterm
      delivery, stillbirth, and low Apgar score. DATA COLLECTION AND ANALYSIS: Two
      authors independently applied selection criteria, extracted data, and assessed
      the quality of the included studies. A third author was available for resolving
      differences of opinion. MAIN RESULTS: Seven studies, including 2 cohort and 5
      case-control studies, of 659,675 participants were included. We did not undertake
      a meta-analysis due to considerable methodological heterogeneity. The available
      data was limited and mainly on orofacial cleft. Most studies did not find
      significant associations between topical corticosteroids and pregnancy outcomes
      including mode of delivery, congenital abnormality, preterm delivery, and
      stillbirth. One study found a significant association between first trimester
      topical corticosteroid use and orofacial cleft, and another found a significant
      association between very potent topical corticosteroids and low birthweight.
      Nevertheless, all the studies had drawbacks, and the quality of evidence was low
      to very low. AUTHORS' CONCLUSIONS: Currently limited and inconclusive data are
      unable to detect an association between topical corticosteroids and congenital
      abnormality, preterm delivery, or stillbirth. The current evidence shows no
      statistically significant difference between pregnant women who use and those who
      do not use topical corticosteroids. However, there does appear to be an
      association of very potent topical corticosteroids with low birthweight. Cohort
      studies with comprehensive outcome measures, assessment of effects of
      corticosteroid potency and dose, application methods, and reasons for giving
      them, and a very large sample size are needed.

PMID- 19588426
TI  - Single dose oral etodolac for acute postoperative pain in adults.
AB  - BACKGROUND: Etodolac is a selective cyclo-oxygenase-2 (COX-2) inhibitor, with
      evidence of efficacy in osteoarthritis and rheumatoid arthritis. Its analgesic
      efficacy in postoperative pain has not been clearly established. There are no
      systematic reviews on Etodolac's use in this condition. OBJECTIVES: To assess the
      analgesic efficacy of etodolac in single oral doses for moderate and severe
      postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE,
      EMBASE and the Oxford Pain Relief Database for studies to May 2009. SELECTION
      CRITERIA: Randomised, double blind, placebo-controlled trials of single dose
      orally administered etodolac (any formulation) in adults with moderate to severe
      acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Pain relief or pain
      intensity data were extracted and converted into the dichotomous outcome of
      number of participants with at least 50% pain relief over 4 to 6 hours, from
      which relative risk (RR) and number needed to treat to benefit (NNT) were
      calculated. Numbers of participants using rescue medication over specified time
      periods, and time to use of rescue medication, were sought as additional measures
      of efficacy. Information on adverse events and withdrawals were collected. MAIN
      RESULTS: Nine studies (1459 participants) compared etodolac and placebo. Studies
      were of adequate reporting quality, and the majority of participants had pain
      following dental extractions. The dose of etodolac used was 25 mg to 1200 mg,
      with most of the information for 100 mg and 200 mg. For at least 50% pain relief
      over 4 to 6 hours compared with placebo the NNT for etodolac 100 mg (498
      participants) was 4.8 (3.5 to 7.8) and for etodolac 200 mg (670 participants) it
      was 3.3 (2.7 to 4.2). Very limited information with the extended release
      formulation did not suggest improved benefit for this outcome.The proportion of
      participants with at least 50% pain relief was 41% with 100 mg and 44% with 200
      mg. Remedication was needed by about 60% with etodolac 200 mg or 400 mg over 6 to
      8 hours, compared with almost 80% with placebo.Adverse events were uncommon, and
      not significantly different form placebo. AUTHORS' CONCLUSIONS: Etodolac 200 mg
      may be a useful analgesic in postoperative pain, with efficacy similar to
      paracetamol 1000 mg and celecoxib 200 mg. Higher doses may provide analgesia
      equivalent to more commonly used drugs, such as ibuprofen 400 mg, naproxen 500 mg
      and diclofenac 50 mg.

PMID- 19588427
TI  - Single dose oral flurbiprofen for acute postoperative pain in adults.
AB  - BACKGROUND: Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug
      (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic
      painful conditions. There is no systematic review of its use in acute
      postoperative pain. OBJECTIVES: To assess efficacy, duration of action, and
      associated adverse events of single dose oral flurbiprofen in acute postoperative
      pain in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE
      and the Oxford Pain Relief Database for studies to January 2009. SELECTION
      CRITERIA: Randomised, double blind, placebo-controlled trials of single dose
      orally administered flurbiprofen in adults with moderate to severe acute
      postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Pain relief or pain
      intensity data were extracted and converted into the dichotomous outcome of
      number of participants with at least 50% pain relief over 4 to 6 hours, from
      which relative risk (RR) and number needed to treat to benefit (NNT) were
      calculated. Numbers of participants using rescue medication over specified time
      periods, and time to use of rescue medication, were sought as additional measures
      of efficacy. Information on adverse events and withdrawals were collected. MAIN
      RESULTS: Eleven studies compared flurbiprofen (699 participants) with placebo
      (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate
      reporting quality, and most participants had pain following dental
      extractions.The dose of flurbiprofen used was 25 mg to 100 mg, with most
      information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to
      6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7
      (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With
      flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50%
      pain relief, compared with 25% to 30% with placebo. Rescue medication was used by
      25% and 16% of participants with flurbiprofen 50 mg and 100 mg over 6 hours,
      compared with almost 70% with placebo.Adverse events were uncommon, and not
      significantly different from placebo. AUTHORS' CONCLUSIONS: Flurbiprofen at doses
      of 50 mg and 100 mg is an effective analgesic in moderate to severe acute
      postoperative pain. The NNT for at least 50% pain relief is similar to that of
      commonly used NSAIDs such as ibuprofen and naproxen at usual doses. Use of rescue
      medication indicates a duration of action exceeding 6 hours.

PMID- 19588428
TI  - Pharmacologic interventions for pregnant women enrolled in alcohol treatment.
AB  - BACKGROUND: Excessive alcohol use during pregnancy has been associated with
      adverse maternal and neonatal effects. It is therefore important to develop and
      evaluate effective interventions during this important time in a woman's life. To
      our knowledge there have been no systematic reviews of randomised control trials
      (RCT) in this population. OBJECTIVES: To evaluate the effectiveness of
      pharmacologic interventions in pregnant women enrolled in alcohol treatment
      programs for improving birth and neonatal outcomes, maternal abstinence and
      treatment retention. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol
      Group's Trial register (August 2008) ; MEDLINE (1.1950 to 6.2008) ; EMBASE
      (1.1974 - 8.2008); CINAHL (1.1982-6.2008); PsycInfo (1.1806-6.2008), and
      reference lists of articles. SELECTION CRITERIA: We sought to include randomised
      or quasi-randomised studies comparing any pharmacologic intervention versus other
      pharmacologic treatment alone or in association with psychosocial treatment,
      placebo, non-intervention or psychosocial intervention. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trials for inclusion in the
      review. Included studies were to be assessed using standardized data extraction
      and quality assessment forms. No suitable trials were identified. MAIN RESULTS:
      The search strategy identified 793 citations. Twenty-three citations were deemed
      relevant for full text review; an additional ten articles were retrieved through
      hand searching references, for a total of thirty-three articles. Following full
      text review no articles met the inclusion criteria. Data extraction and
      assessment of methodological quality were therefore not possible. AUTHORS'
      CONCLUSIONS: The review question remains unanswered as there were no randomised
      control trials found relevant to the topic. There is a need for high quality
      research to determine the effectiveness of pharmacologic interventions in
      pregnant women enrolled in alcohol treatment program.

PMID- 19588429
TI  - Interventions for pain with intrauterine device insertion.
AB  - BACKGROUND: Fear of pain during intrauterine device (IUD) insertion is a barrier
      to use of this contraceptive method. Interventions for pain during IUD insertion
      include non-steroidal anti-inflammatory drugs (NSAIDs), local cervical
      anesthetics, and cervical ripening agents such as misoprostol. OBJECTIVES: To
      review all randomized controlled trials that have evaluated a treatment for IUD
      insertion-related pain. SEARCH STRATEGY: We searched the computerized databases
      MEDLINE, POPLINE, CENTRAL, and EMBASE for relevant trials. We also examined
      reference lists of pertinent articles and wrote to known investigators for
      information about other published or unpublished trials. SELECTION CRITERIA: We
      included all randomized controlled trials in any language that evaluated a
      treatment for IUD insertion-related pain. The intervention could be compared to a
      placebo or another active intervention. DATA COLLECTION AND ANALYSIS: Two authors
      independently abstracted data from relevant trials and data were entered into
      RevMan 5.0 for analysis. For dichotomous variables, the Peto odds ratios with 95%
      confidence intervals was calculated. For continuous variables, the mean
      differences with 95% confidence interval was computed. MAIN RESULTS: Four trials
      met the inclusion criteria; the total number of participants was 2204.
      Nonsteroidal anti-inflammatory drugs of varying types and doses were not
      effective for reducing pain during IUD insertion. Misoprostol for cervical
      ripening did not reduce pain with IUD insertion in nulliparous women. Two trials
      evaluated pain that occurs after IUD insertion using nonsteroidal anti
      inflammatory drugs. In one trial, naproxen taken prior to IUD insertion was
      effective in reducing pain compared with placebo in the first two hours after IUD
      insertion in mostly nulliparous women. However, this trial utilized the Dalkon
      Shield, an IUD with a wider diameter than modern IUDs. In another trial,
      ibuprofen 600 mg taken before IUD insertion did not show evidence of an effect on
      pain four to six hours after IUD insertion. AUTHORS' CONCLUSIONS: No
      interventions that have been properly evaluated reduce pain during or after IUD
      insertion. One poorly controlled trial suggested that topical lidocaine gel may
      reduce insertion-related pain and warrants further investigation.

PMID- 19588430
TI  - Topical rubefacients for acute and chronic pain in adults.
AB  - BACKGROUND: Rubefacients (containing salicylates or nicotinamides) cause
      irritation of the skin, and are believed to relieve various musculoskeletal
      pains. They are available on prescription, and are common components in over-the
      counter remedies. A non-Cochrane review in 2004 found limited evidence for
      efficacy. OBJECTIVES: To review current evidence for efficacy and safety of
      topically applied rubefacients in acute and chronic painful musculoskeletal
      conditions in adults. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, the
      Oxford Pain Relief Database, and reference lists of articles were searched; last
      search December 2008. SELECTION CRITERIA: Randomised, double blind, placebo or
      active controlled clinical trials of topical rubefacient for musculoskeletal pain
      in adults, with at least 10 participants per treatment arm, and reporting
      outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14
      (minimum 7) days or longer for chronic conditions. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trials for inclusion and quality, and
      extracted data. Relative benefit or risk and number needed to treat to benefit or
      harm (NNT or NNH) were calculated with 95% confidence intervals (CI). Acute and
      chronic conditions were analysed separately. MAIN RESULTS: Six placebo and one
      active controlled studies (560 and 137 participants) in acute pain, and seven
      placebo and two active controlled studies (489 and 90 participants) in chronic
      pain were included. All used topical salicylates. The evidence in acute
      conditions was not robust; using only better quality, valid studies, there was no
      difference between topical rubefacient and topical control, though overall,
      including lower quality studies, the NNT for clinical success compared with
      placebo was 3.2 (95% CI: 2.4 to 4.9). In chronic conditions the NNT was 6.2 (95%
      CI: 4.0 to 13) compared with topical placebo. Adverse events and withdrawals
      occurred more often with rubefacients than placebo, but analyses were sensitive
      to inclusion of individual studies, so not robust. There were insufficient data
      to draw conclusions against active controls. AUTHORS' CONCLUSIONS: The evidence
      does not support the use of topical rubefacients containing salicylates for acute
      injuries, and suggests that in chronic conditions their efficacy compares poorly
      with topical non-steroidal antiinflammatory drugs (NSAIDs). Topical salicylates
      seem to be relatively well tolerated in the short-term, based on limited data.
      There is no evidence at all for topical rubefacients with other components.

PMID- 19588431
TI  - Single dose oral nefopam for acute postoperative pain in adults.
AB  - BACKGROUND: Nefopam is a centrally-acting but non-opioid analgesic drug of the
      benzoxazocine chemical class, developed in the early 1970s. It is widely used,
      mainly in European countries, for the relief of moderate to severe pain as an
      alternative to opioid analgesic drugs, and used in rheumatic disease and other
      musculoskeletal disorders in the UK. This review sought to evaluate the efficacy
      and safety of oral nefopam in acute postoperative pain, using clinical studies of
      patients with established pain, and with outcomes measured primarily over 6 hours
      using standard methods. This type of study has been used for many decades to
      establish that drugs have analgesic properties. OBJECTIVES: To assess the
      efficacy of single dose oral nefopam in acute postoperative pain, and any
      associated adverse events. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2009),
      MEDLINE (1966 to May 2009); EMBASE via Ovid (1980 to May 2009); the Oxford Pain
      Relief Database (1950 to 1994); and reference lists of studies found. SELECTION
      CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of oral
      nefopam for relief of acute postoperative pain in adults. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and extracted
      data. The area under the "pain relief versus time" curve was used to derive the
      proportion of participants with nefopam and placebo experiencing least 50% pain
      relief over 4 to 6 hours, using validated equations. The number-needed-to-treat
      to-benefit (NNT) was calculated using 95% confidence intervals (CIs). The
      proportion of participants using rescue analgesia over a specified time period,
      and time to use of rescue analgesia, were sought as additional measures of
      efficacy. Information on adverse events and withdrawals was also collected. MAIN
      RESULTS: No included studies were identified after examining in detail thirteen
      studies on oral nefopam in participants with established postoperative pain.
      AUTHORS' CONCLUSIONS: In the absence of evidence of efficacy for oral nefopam in
      acute postoperative pain, its use in this indication is not justified. Because
      trials clearly demonstrating analgesic efficacy in the most basic of acute pain
      studies are lacking, use in other indications should be evaluated carefully.
      Given the large number of available drugs of this and similar classes, there is
      no urgent research agenda.

PMID- 19588432
TI  - Intrapartum antibiotics for known maternal Group B streptococcal colonization.
AB  - BACKGROUND: Maternal colonization with group B streptococcus (GBS) during
      pregnancy increases the risk of neonatal infection by vertical transmission.
      Administration of intrapartum antibiotic prophylaxis (IAP) during labor has been
      associated with a reduction in early onset GBS disease (EOGBSD). However,
      treating all colonized women during labor exposes a large number of women and
      infants to possible adverse effects without benefit. OBJECTIVES: To assess the
      effect of IAP for maternal GBS colonization on neonatal: 1) all cause mortality
      and 2) morbidity from proven and probable EOGBSD, late onset GBS disease (LOD),
      maternal infectious outcomes and allergic reactions to antibiotics. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (April 2009). SELECTION CRITERIA: Randomized trials assessing the impact
      of maternal IAP on neonatal GBS infections were included. DATA COLLECTION AND
      ANALYSIS: We independently assessed eligibility and quality of the studies. MAIN
      RESULTS: Three trials (involving 852 women) evaluating the effects of IAP versus
      no treatment were included. The risk of bias was high. The use of IAP did not
      significantly reduce the incidence of all cause mortality, mortality from GBS
      infection or from infections caused by bacteria other than GBS. The incidence of
      early GBS infection was reduced with IAP compared to no treatment (risk ratio
      0.17, 95% confidence interval (CI) 0.04 to 0.74, three trials, 488 infants; risk
      difference -0.04, 95% CI -0.07 to -0.01; number needed to treat to benefit 25,
      95% CI 14 to 100, I(2) 0%). The incidence of LOD or sepsis from organisms other
      than GBS and puerperal infection was not significantly different between
      groups.One trial (involving 352 women) compared intrapartum ampicillin versus
      penicillin and reported no significant difference in neonatal or maternal
      outcomes. AUTHORS' CONCLUSIONS: Intrapartum antibiotic prophylaxis appeared to
      reduce EOGBSD, but this result may well be a result of bias as we found a high
      risk of bias for one or more key domains in the study methodology and execution.
      There is lack of evidence from well designed and conducted trials to recommend
      IAP to reduce neonatal EOGBSD.Ideally the effectiveness of IAP to reduce neonatal
      GBS infections should be studied in adequately sized double-blind controlled
      trials. The opportunity to conduct such trials has likely been lost, as practice
      guidelines (albeit without good evidence) have been introduced in many
      jurisdictions.

PMID- 19588433
TI  - Artemisinin-based combination therapy for treating uncomplicated malaria.
AB  - BACKGROUND: The World Health Organization recommends uncomplicated P. falciparum
      malaria is treated using Artemisinin-based Combination Therapy (ACT). This review
      aims to assist the decision making of malaria control programmes by providing an
      overview of the relative benefits and harms of the available options. OBJECTIVES:
      To compare the effects of ACTs with other available ACT and non-ACT combinations
      for treating uncomplicated P. falciparum malaria. SEARCH STRATEGY: We searched
      the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central
      Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS, and the
      metaRegister of Controlled Trials (mRCT) to March 2009. SELECTION CRITERIA:
      Randomized head to head trials of ACTs in uncomplicated P. falciparum
      malaria.This review is limited to: dihydroartemisinin-piperaquine; artesunate
      plus mefloquine; artemether-lumefantrine (six doses); artesunate plus
      amodiaquine; artesunate plus sulfadoxine-pyrimethamine and amodiaquine plus
      sulfadoxine-pyrimethamine. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trials for eligibility and risk of bias, and extracted
      data. We analysed primary outcomes in line with the WHO 'Protocol for assessing
      and monitoring antimalarial drug efficacy' and compared drugs using risk ratios
      (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on P.
      vivax, gametocytes, haemoglobin, and adverse events. MAIN RESULTS: Fifty studies
      met the inclusion criteria. All five ACTs achieved PCR adjusted failure rates of
      < 10%, in line with WHO recommendations, at most study sites.Dihydroartemisinin
      piperaquine performed well compared to the ACTs in current use (PCR adjusted
      treatment failure versus artesunate plus mefloquine in Asia; RR 0.39, 95% CI 0.19
      to 0.79; three trials, 1062 participants; versus artemether-lumefantrine in
      Africa; RR 0.39, 95% CI 0.24 to 0.64; three trials, 1136 participants).ACTs were
      superior to amodiaquine plus sulfadoxine-pyrimethamine in East Africa (PCR
      adjusted treatment failure versus artemether-lumefantrine; RR 0.12, 95% CI 0.06
      to 0.24; two trials, 618 participants; versus AS+AQ; RR 0.44, 95% CI 0.22 to
      0.89; three trials, 1515 participants).Dihydroartemisinin-piperaquine (RR 0.32,
      95% CI 0.24 to 0.43; four trials, 1442 participants) and artesunate plus
      mefloquine (RR 0.30, 95% CI 0.21 to 0.41; four trials, 1003 participants) were
      more effective than artemether-lumefantrine at reducing the incidence of P.vivax
      over 42 days follow up. AUTHORS' CONCLUSIONS: Dihydroartemisinin-piperaquine is
      another effective first-line treatment for P. falciparum malaria.The performance
      of the non-ACT (amodiaquine plus sulfadoxine-pyrimethamine) falls below WHO
      recommendations for first-line therapy in parts of Africa.In areas where
      primaquine is not being used for radical cure of P. vivax, ACTs with long half
      lives may provide some benefit.

PMID- 19588435
TI  - Methotrexate for maintenance of remission in ulcerative colitis.
AB  - BACKGROUND: Methotrexate, a folate antagonist, is an immunosuppressant drug that
      is effective for treating several inflammatory disorders including Crohn's
      disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be
      challenging to treat. This review was performed to examine the efficacy of
      methotrexate for maintenance of remission in ulcerative colitis. OBJECTIVES: To
      systematically review randomized controlled trials examining the efficacy and
      safety of methotrexate for maintenance of remission in patients with ulcerative
      colitis. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials
      (CENTRAL) and the Cochrane IBD/FBD Review Group Specialized Trials Register,
      MEDLINE (PUBMED), EMBASE (1984 to November 2008), Web of Science, Scopus,
      Database of Abstracts of Reviews of Effects (DARE), and Clinical trials database
      (ClinicalTrials.gov) were searched. In addition, references from selected papers
      and abstracts from Digestive Disease Week were also examined. SELECTION CRITERIA:
      Only randomized controlled trials (RCT) evaluating the efficacy of methotrexate
      for maintaining remission in patients with ulcerative colitis compared to placebo
      or any other intervention were considered for inclusion in this review. DATA
      COLLECTION AND ANALYSIS: Data were extracted independently by each author. The
      odds ratio of relapse, 95% confidence interval and P-value were calculated using
      the Mantel-Haenszel method. An intention to treat analysis was used. MAIN
      RESULTS: Only one trial fulfilled the inclusion criteria. This trial randomized
      30 patients to methotrexate and 37 to placebo. Methotrexate was given orally in a
      dose of 12.5 mg/week. Fourteen patients in the methotrexate group and 18 patients
      in the placebo group who entered remission were followed for 9 months or to the
      time of first relapse. Sixty-four per cent of methotrexate patients relapsed
      compared to 44% of placebo patients (OR 2.25; 95% CI 0.54 to 9.45; P = 0.27).
      AUTHORS' CONCLUSIONS: The available evidence is not sufficient to recommend the
      use of methotrexate to maintain remission in patients with ulcerative colitis. A
      large scale methodologically rigorous randomized controlled trial is needed. Such
      a study should investigate higher doses of methotrexate and parenteral
      administration.

PMID- 19588434
TI  - Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in
      adults.
AB  - BACKGROUND: Dexibuprofen (S(+)-ibuprofen) is a non-steroidal anti-inflammatory
      drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal
      disorders in the UK, and widely available in other countries worldwide. It is an
      active isomer of ibuprofen. This review sought to evaluate the efficacy and
      safety of oral dexibuprofen in acute postoperative pain, using clinical studies
      of patients with established pain, and with outcomes measured primarily over 6
      hours using standard methods. This type of study has been used for many decades
      to establish that drugs have analgesic properties. OBJECTIVES: To assess
      efficacy, duration of action, and associated adverse events of single dose oral
      dexibuprofen in acute postoperative pain in adults. SEARCH STRATEGY: We searched
      Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies
      to May 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled
      clinical trials of oral dexibuprofen for relief of acute postoperative pain in
      adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial quality and extracted data. Pain relief or pain intensity data were
      extracted and converted into the dichotomous outcome of number of participants
      with at least 50% pain relief over 4 to 6 hours, from which relative risk and
      number needed to treat to benefit (NNT) were calculated. Numbers of participants
      using rescue medication over specified time periods, and time to use of rescue
      medication, were sought as additional measures of efficacy. Information on
      adverse events and withdrawals were collected. MAIN RESULTS: In the single
      included study, both S(+)-ibuprofen (dexibuprofen, an active isomer of ibuprofen)
      200 mg and 400 mg gave high levels of response, with 31/51 (61%) and 35/50 (70%)
      respectively having at least 50% pain relief over 4 to 6 hours, compared with
      2/25 (8%) with placebo. The median time to additional analgesic use was 5.8
      hours, 6.1 hours, and 1.8 hours respectively. The numbers of participants was too
      small to calculate NNTs with any meaning. AUTHORS' CONCLUSIONS: The information
      from the single trial in acute postoperative pain suggests it to be a useful
      analgesic, but at doses not very different from racemic ibuprofen.

PMID- 19588436
TI  - Single dose oral aceclofenac for postoperative pain in adults.
AB  - BACKGROUND: Aceclofenac is the prodrug of the non-steroidal anti-inflammatory
      drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are
      no known systematic reviews of its analgesic efficacy in acute postoperative
      pain. This review sought to evaluate the efficacy and safety of oral aceclofenac
      in acute postoperative pain, using clinical studies of patients with established
      pain, and with outcomes measured primarily over 6 hours using standard methods.
      This type of study has been used for many decades to establish that drugs have
      analgesic properties. OBJECTIVES: To assess the efficacy of single dose oral
      aceclofenac in acute postoperative pain, and any associated adverse events.
      SEARCH STRATEGY: We searched The Cochrane Library (Issue 1, 2009), MEDLINE via
      Ovid (1966 to March 2009); EMBASE via Ovid (1980 to March 2009); the Oxford Pain
      Relief Database (1950 to 1994); and reference lists of articles. SELECTION
      CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of oral
      aceclofenac for relief of acute postoperative pain in adults. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and extracted
      data. The area under the "pain relief versus time" curve was used to derive the
      proportion of participants with paracetamol plus codeine and placebo or
      paracetamol alone experiencing least 50% pain relief over 4 to 6 hours, using
      validated equations. The number needed to treat to benefit (NNT) was calculated
      using 95% confidence intervals (CI). The proportion of participants using rescue
      analgesia over a specified time period, and time to use of rescue analgesia, were
      sought as additional measures of efficacy. Information on adverse events and
      withdrawals was also collected. MAIN RESULTS: Searches identified only one study
      (217 participants total), which used oral aceclofenac 150 mg in patients with
      established postoperative pain. Aceclofenac 150 mg could not be distinguished
      from placebo, though ibuprofen 400 mg was distinguished from placebo. AUTHORS'
      CONCLUSIONS: In the absence of evidence of efficacy for oral aceclofenac in acute
      postoperative pain (at least at 150 mg single dose), its use in this indication
      is not justified. Because trials clearly demonstrating analgesic efficacy in the
      most basic of acute pain studies are lacking, use in other indications should be
      evaluated carefully. Given the large number of effective drugs available in this
      and similar classes of analgesics, there is no urgent research agenda required to
      demonstrate the effective dose of aceclofenac in acute postoperative pain.

PMID- 19588437
TI  - Single dose oral acemetacin for acute postoperative pain in adults.
AB  - BACKGROUND: Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) licensed
      for use in rheumatic disease and other musculoskeletal disorders in the UK, and
      widely available in other countries worldwide. This review sought to evaluate the
      efficacy and safety of oral acemetacin in acute postoperative pain, using
      clinical studies of patients with established pain, and with outcomes measured
      primarily over 6 hours using standard methods. This type of study has been used
      for many decades to establish that drugs have analgesic properties. OBJECTIVES:
      To assess the efficacy of single dose oral acemetacin in acute postoperative
      pain, and any associated adverse events. SEARCH STRATEGY: We searched CENTRAL
      (Issue 2, 2009), MEDLINE via Ovid (1966 to May 2009); EMBASE via Ovid (1980 to
      May 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of
      articles. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled
      clinical trials of oral acemetacin for relief of acute postoperative pain in
      adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial quality and extracted data. The area under the "pain relief versus time"
      curve was used to derive the proportion of participants with acemetacin and
      placebo experiencing least 50% pain relief over 4 to 6 hours, using validated
      equations. The number needed to treat to benefit (NNT) was calculated using 95%
      confidence intervals. The proportion of participants using rescue analgesia over
      a specified time period, and time to use of rescue analgesia, were sought as
      additional measures of efficacy. Information on adverse events and withdrawals
      was also collected. MAIN RESULTS: No study fulfilled the inclusion criteria.
      AUTHORS' CONCLUSIONS: In the absence of randomised evidence of efficacy for oral
      acemetacin in acute postoperative pain, we cannot, at present, make any
      conclusions regarding its effectiveness. Because trials clearly demonstrating
      analgesic efficacy in the most basic of acute pain studies is lacking, use in
      other indications should be evaluated carefully. Given the large number of
      available drugs of this kind and similar classes, there is no urgent research
      agenda for this drug.

PMID- 19588438
TI  - Single dose oral tenoxicam for acute postoperative pain in adults.
AB  - BACKGROUND: Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) licensed
      for use in rheumatic disease and other musculoskeletal disorders in the UK, and
      is widely available in other countries worldwide. This review sought to evaluate
      the efficacy and safety of oral tenoxicam in acute postoperative pain, using
      clinical studies of patients with established pain, and with outcomes measured
      primarily over 6 hours using standard methods. This type of study has been used
      for many decades to establish that drugs have analgesic properties. OBJECTIVES:
      To assess the efficacy of single dose oral tenoxicam in acute postoperative pain,
      and any associated adverse events. SEARCH STRATEGY: We searched The Cochrane
      Library (Issue 1, 2009), MEDLINE (March 2009); EMBASE via Ovid (March 2009); the
      Oxford Pain Relief Database. SELECTION CRITERIA: Randomised, double-blind,
      placebo-controlled clinical trials of oral tenoxicam for relief of acute
      postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. The area under the "pain
      relief versus time" curve was used to derive the proportion of participants with
      tenoxicam experiencing least 50% pain relief over 4 to 6 hours, using validated
      equations. The number needed to treat to benefit (NNT) was calculated using 95%
      confidence intervals (CI). The proportion of participants using rescue analgesia
      over a specified time period, and time to use of rescue analgesia, were sought as
      additional measures of efficacy. Information on adverse events and withdrawals
      was also collected. MAIN RESULTS: Not one of sixteen studies identified by the
      searches and examined in detail studied oral tenoxicam in patients with
      established postoperative pain and therefore no results are available. AUTHORS'
      CONCLUSIONS: In the absence of evidence of efficacy for oral tenoxicam in acute
      postoperative pain, its use in this indication is not justified at present.
      Because trials clearly demonstrating analgesic efficacy in the most basic of
      acute pain studies is lacking, use in other indications should be evaluated
      carefully. Given the large number of available drugs of this and similar classes
      which are effective, there is no urgent research agenda for this particular drug.

PMID- 19588439
TI  - Interventions for prevention of neonatal hyperglycemia in very low birth weight
      infants.
AB  - BACKGROUND: Among very low birth weight (VLBW) infants, early neonatal
      hyperglycemia is common and is associated with increased risks for death and
      major morbidities. It is uncertain whether hyperglycemia per se is a cause of
      adverse clinical outcomes or whether outcomes can be improved by preventing
      hyperglycemia. OBJECTIVES: To assess effects on clinical outcomes of
      interventions for preventing hyperglycemia in VLBW neonates receiving full or
      partial parenteral nutrition. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library, issue 4 2008;
      MEDLINE (1966 - Nov 2008); EMBASE (1980 - Nov 2008); CINAHL (1982 - Nov 2008);
      abstracts of Pediatric Academic Societies 2000 - 2008 and European Society for
      Paediatric Research 2005 - 2008. SELECTION CRITERIA: Randomized or quasi
      randomized controlled trials of interventions for prevention of hyperglycemia in
      neonates with birth weight < 1500 g or gestational age < 32 wk DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected studies for eligibility
      and extracted data on study design, methods, clinical features, and treatment
      outcomes. Included trials were assessed for blinding of randomization,
      intervention and outcome measurement, and completeness of follow-up. Treatment
      effect measures for categorical outcomes were relative risk and risk difference,
      and for continuous outcomes, mean difference, each with their 95% confidence
      intervals. MAIN RESULTS: We detected four eligible trials. Two trials compared
      lower vs. higher rates of glucose infusion in the early postnatal period. These
      trials were too small to assess effects on mortality or major morbidities. Two
      trials, one a moderately large multicentre trial (NIRTURE, Beardsall 2008),
      compared insulin infusion with standard care. Insulin infusion reduced
      hyperglycemia but increased death before 28 days and hypoglycemia. Reduction in
      hyperglycemia was not accompanied by significant effects on major morbidities;
      effects on neurodevelopment are awaited. AUTHORS' CONCLUSIONS: Glucose infusion
      rate: There is insufficient evidence from trials comparing lower with higher
      glucose infusion rates to inform clinical practice. Large randomized trials are
      needed, powered on clinical outcomes including death, major morbidities and
      adverse neurodevelopment.Insulin infusion: The evidence reviewed does not support
      the routine use of insulin infusions to prevent hyperglycemia in VLBW neonates.
      Further randomized trials of insulin infusion may be justified. They should enrol
      extremely low birth weight neonates at very high risk for hyperglycemia and
      neonatal death. They might use real time glucose monitors if these are validated
      for clinical use. Refinement of algorithms to guide insulin infusion is needed to
      enable tight control of glucose concentrations within the target range.

PMID- 19588440
TI  - Long-term effects of weight-reducing drugs in hypertensive patients.
AB  - BACKGROUND: All major guidelines for antihypertensive therapy recommend weight
      loss; anti-obesity drugs might be a helpful option. OBJECTIVES:  PRIMARY
      OBJECTIVES: To assess the long-term effects of pharmacologically induced
      reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause
      mortality - cardiovascular morbidity - adverse events SECONDARY OBJECTIVES: -
      changes in systolic and/or diastolic blood pressure - body weight reduction
      SEARCH STRATEGY: Studies were obtained from computerised searches of Ovid
      MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic
      reviews. SELECTION CRITERIA: Randomized controlled trials in adult hypertensive
      patients with a study duration of at least 24 weeks comparing pharmacologic
      interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and
      extracted data. Studies were pooled using fixed-effect meta-analysis in the
      absence of significant heterogeneity between studies (p>0.1). Otherwise, we used
      the random effects method and investigated the cause of heterogeneity. MAIN
      RESULTS: Eight studies comparing orlistat or sibutramine to placebo fulfilled our
      inclusion criteria. No relevant studies investigating rimonabant for weight loss
      were identified. No study included mortality and cardiovascular morbidity as a
      pre-defined outcome. Incidence of gastrointestinal side effects was consistently
      higher in orlistat treated vs. placebo treated patients. Most frequent side
      effects with sibutramine were dry mouth, constipation and headache. Patients
      assigned to weight loss diets, orlistat or sibutramine reduced their body weight
      more effectively than patients in the usual care/placebo groups. Blood pressure
      reduction in patients treated with orlistat was for systolic blood pressure
      (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and
      for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg.
      Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg;
      95%CI +1.4 to +4.9 mm Hg. AUTHORS' CONCLUSIONS: In patients with elevated blood
      pressure, orlistat and sibutramine reduced body weight to a similar degree. In
      the same trials, orlistat reduced blood pressure and sibutramine increased blood
      pressure. No trials investigating rimonabant in people with elevated blood
      pressure could be included. Long-term trials assessing the effect of orlistat,
      sibutramine and rimonabant on mortality and morbidity are needed.

PMID- 19588441
TI  - Pentoxifylline versus medical therapies for subfertile women with endometriosis.
AB  - BACKGROUND: Endometriosis is a chronic, recurring condition that occurs during
      the reproductive years. It is characterized by endometrial tissue developing
      outside the uterine cavity. This endometrial tissue development is dependent on
      estrogen produced primarily by the ovaries and, therefore, traditional management
      has focused on ovarian suppression. In this review we considered the role of
      modulation of the immune system as an alternative approach. OBJECTIVES: To
      determine the effectiveness and safety of pentoxifylline, which has anti
      inflammatory effects, in the management of endometriosis in subfertile,
      premenopausal women. SEARCH STRATEGY: We searched the following databases (from
      inception to December 2008) for trials: Cochrane Menstrual Disorders and
      Subfertility Group Specialised Register, Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO.
      In addition, all reference lists of included trials were searched and experts in
      the field were contacted in an attempt to locate trials. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no
      treatment, medical treatment, or surgery in subfertile, premenopausal women were
      included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
      trials for inclusion, assessed trial quality, and extracted data using data
      extraction forms. We contacted study authors for additional information and data.
      The domains assessed for risk of bias were sequence generation, allocation
      concealment, blinding, incomplete outcome data, and selective outcome reporting.
      Odds ratios (OR) were used for reporting dichotomous data with 95% confidence
      intervals (CI), whilst mean differences (MD) were expressed for continuous data.
      Statistical heterogeneity was assessed using the I(2) statistic. MAIN RESULTS:
      Four trials involving 334 participants were included. Results showed
      pentoxifylline had no significant effect on reduction in pain (one RCT, MD -1.60,
      95% CI -3.32 to 0.12). There was no evidence of an increase in clinical pregnancy
      events in the pentoxifylline group compared with placebo (three RCTs, OR 1.54,
      95% CI 0.89 to 266). For recurrence of endometriosis, one RCT reported an OR of
      0.88 (95% CI 0.27 to 2.84). No trials reported the effects of pentoxifylline on
      the odds of live birth rate per woman, improvement of endometriosis-related
      symptoms, or adverse events. AUTHORS' CONCLUSIONS: There is not enough evidence
      to support the use of pentoxifylline in the management of premenopausal women
      with endometriosis in terms of subfertility and relief of pain outcomes.

PMID- 19588442
TI  - Danazol for uterine fibroids.
AB  - BACKGROUND: Uterine fibroids (myomas, fibromyomas, leiomyomas) are the most
      common benign tumours of the female genital tract. Danazol, a synthetic isoxazole
      derivative chemically related to 17-ethinyl testosterone, has been used for many
      years for the treatment of women with uterine fibroids. OBJECTIVES: To evaluate
      the effectiveness and safety of danazol in women with uterine fibroids. SEARCH
      STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Review
      Group Specialised Register; Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; Chinese
      Biomedical Disc; and the China National Knowledge Infrastructure for relevant
      trials (to December 2008). Attempts were made to identify trials from references
      in published studies. We also searched for ongoing trials in the five major
      clinical trials registries. SELECTION CRITERIA: Randomised controlled trials of
      danazol versus placebo or any other medical therapy in women with uterine
      fibroids confirmed by medical procedures, regardless of the women's symptoms or
      age. Women with malignancies were excluded. DATA COLLECTION AND ANALYSIS: Data
      extraction and risk of bias assessment were not been performed because there were
      no identified studies. MAIN RESULTS: We did not identify any studies which met
      our full inclusion criteria. AUTHORS' CONCLUSIONS: There is no reliable evidence
      available from randomised controlled trials regarding the benefits and or harms
      of the use of danazol for treating uterine fibroids.

PMID- 19588443
TI  - Antibacterial agents in composite restorations for the prevention of dental
      caries.
AB  - BACKGROUND: Dental caries is a multifactorial disease in which the fermentation
      of food sugars by bacteria from the biofilm (dental plaque) leads to localised
      demineralisation of tooth surfaces, which may ultimately result in cavity
      formation. Resin composites are widely used in dentistry to restore teeth. These
      restorations can fail for a number of reasons, such as secondary caries,
      excessive wear, marginal degradation, tooth sensitivity, pulpal death, and
      restorative material fracture. Caries adjacent to restorations is one of the main
      causes for restoration replacement. The presence of antibacterials in both the
      filling material and the bonding systems would theoretically be able to affect
      the initiation and progression of caries adjacent to restorations. OBJECTIVES: To
      assess the effects of antibacterial agents incorporated into composite
      restorations for the prevention of dental caries. SEARCH STRATEGY: We searched
      the following databases in February 2009: the Cochrane Oral Health Group's Trials
      Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2009, Issue 1); MEDLINE via OVID (1950 to February 2009) without
      filter; and EMBASE via OVID (1980 to February 2009) without filter. SELECTION
      CRITERIA: Randomised controlled clinical trials (RCTs) comparing resin composite
      restorations containing antibacterial agents with non-antibacterial containing
      composite restorations. DATA COLLECTION AND ANALYSIS: Two review authors
      conducted screening of studies in duplicate and independently, and although no
      eligible trials were identified, the two authors had planned to extract data
      independently and assess trial quality using standard Cochrane Collaboration
      methodologies. MAIN RESULTS: We retrieved 128 references to studies, none of
      which matched the inclusion criteria for this review and all of which were
      excluded. AUTHORS' CONCLUSIONS: We were unable to identify any randomised
      controlled trials on the effects of antibacterial agents incorporated into
      composite restorations for the prevention of dental caries. The absence of high
      level evidence for the effectiveness of this intervention emphasises the need for
      well designed, adequately powered, randomised controlled clinical trials.

PMID- 19588444
TI  - Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy
      (SCT) for unresectable liver metastases from colorectal cancer.
AB  - BACKGROUND: Although locoregional treatments such as hepatic arterial infusion
      (HAI) claim the advantage of delivering higher doses of anticancer agents
      directly into the metastatic organ as compared to systemic chemotherapy (SCT),
      the benefit in terms of overall survival (OS) is unclear. We quantitatively
      summarized the results of randomised controlled trials (RCT) comparing HAI to SCT
      for the treatment of unresectable liver metastatic disease from colorectal cancer
      (CRC). OBJECTIVES: The aim of this work is to quantitatively summarize the
      results of RCT comparing HAI to SCT for the treatment of unresectable hepatic
      metastases from CRC. SEARCH STRATEGY: A systematic review of reports published
      until September 2008 on the findings of RCT that compared HAI to SCT for the
      treatment of unresectable CRC liver metastases was performed by searching the
      MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as
      well as other databanks collecting information on clinical trials. SELECTION
      CRITERIA: Inclusion criteria were patients with unresectable CRC liver metastases
      enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response
      rate and overall survival. DATA COLLECTION AND ANALYSIS: Two authors
      independently carried out study selection and assessment of methodological
      quality. A third author performed a concordance analysis in order to unravel
      potential systematic biases. MAIN RESULTS: Ten RCT were identified that met the
      eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5
      fluorouracil or either one of these two fluoropyrimidines in eight and one RCT,
      respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT,
      respectively. By pooling the summary data, tumor response rate resulted 42.9% and
      18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P <
      0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT,
      respectively: the meta-risk of death was not statistically different between the
      two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). AUTHORS'
      CONCLUSIONS: Currently available evidence does not support the clinical or
      investigational use of fluoropyrimidine-based HAI alone for the treatment of
      patients with unresectable CRC liver metastases: in fact, the greater tumor
      response rate obtained with this HAI regimen does not translate into a survival
      advantage over fluoropyrimidine alone SCT.

PMID- 19588445
TI  - Exercise for osteoarthritis of the hip.
AB  - BACKGROUND: Current international treatment guidelines recommending therapeutic
      exercise for people with symptomatic hip OA report are based on expert opinion
      only. OBJECTIVES: To determine whether land-based therapeutic exercise is
      beneficial for people with hip OA in terms of reduced joint pain and/or improved
      physical function. SEARCH STRATEGY: Five databases were searched from 1966 up
      until August 2008. SELECTION CRITERIA: All randomised controlled trials (RCTs)
      recruiting people with hip OA and comparing some form of land-based therapeutic
      exercise (as opposed to exercises conducted in the water) with a non-exercise
      group. DATA COLLECTION AND ANALYSIS: Three reviewers independently extracted data
      and assessed methodological quality. All analyses were conducted on continuous
      outcomes. MAIN RESULTS: Combining the results of the five included RCTs
      demonstrated a small treatment effect for pain, but no benefit in terms of
      improved self-reported physical function. Only one of these five RCTs exclusively
      recruited people with symptomatic hip OA. AUTHORS' CONCLUSIONS: The limited
      number and small sample size of the included RCTs restricts the confidence that
      can be attributed to these results. Adequately powered RCTs evaluating exercise
      programs specifically designed for people with symptomatic hip OA need to be
      conducted.

PMID- 19588446
TI  - Skin preparation with alcohol versus alcohol followed by any antiseptic for
      preventing bacteraemia or contamination of blood for transfusion.
AB  - BACKGROUND: Blood for transfusion may become contaminated at any point between
      collection and transfusion and may result in bacteraemia (the presence of
      bacteria in the blood), severe illness or even death for the blood recipient.
      Donor arm skin is one potential source of blood contamination, so it is usual to
      cleanse the skin with an antiseptic before blood donation. One-step and two-step
      alcohol based antiseptic regimens are both commonly advocated but there is
      uncertainty as to which is most effective. OBJECTIVES: To assess the effects of
      cleansing the skin of blood donors with alcohol in a one-step compared with
      alcohol in a two-step procedure to prevent contamination of collected blood or
      bacteraemia in the recipient. SEARCH STRATEGY: We searched the Cochrane Wounds
      Group Specialised Register (March 10 2009); The Cochrane Central Register of
      Controlled Trials (CENTRAL) The Cochrane Library 2009, Issue 1; Ovid MEDLINE -
      (1950 to February Week 4 2009); Ovid EMBASE - (1980 to 2009 Week 9); and EBSCO
      CINAHL - (1982 to February Week 4 2009). We also searched the reference lists of
      key papers. SELECTION CRITERIA: All randomised trials (RCTs) comparing alcohol
      based donor skin cleansing in a one-step versus a two-step process that includes
      alcohol and any other antiseptic for pre-venepuncture skin cleansing were
      considered. Quasi randomised trials were to have been considered in the absence
      of RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      studies for inclusion. MAIN RESULTS: No studies (RCTs or quasi RCTs) met the
      inclusion criteria. AUTHORS' CONCLUSIONS: We did not identify any eligible
      studies for inclusion in this review. It is therefore unclear whether a two-step,
      alcohol followed by antiseptic skin cleansing process prior to blood donation
      confers any reduction in the risk of blood contamination or bacteraemia in blood
      recipients, or conversely whether a one-step process increases risk above that
      associated with a two-step process.

PMID- 19588447
TI  - Addition of long-acting beta-agonists to inhaled corticosteroids for chronic
      asthma in children.
AB  - BACKGROUND: Long-acting ss(2)- agonists (LABA) in combination with inhaled
      corticosteroids (ICS) are increasingly prescribed in asthmatic children.
      OBJECTIVES: To compare the safety and benefit of adding LABA to ICS with the same
      or an increased dose of ICS in children with persistent asthma. SEARCH STRATEGY:
      We searched the Cochrane Airways Group Asthma Trials Register (May 2008).
      SELECTION CRITERIA: We included randomised controlled trials testing the
      combination of LABA and ICS versus the same or an increased dose of ICS for
      minimum of at least 28 days in children and adolescents with asthma. The main
      outcome was the rate of exacerbations requiring rescue oral steroids. Secondary
      outcomes included pulmonary function, symptoms, adverse events, and withdrawals.
      DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two review
      authors for methodological quality and data extraction. Confirmation was obtained
      from the trialists when possible. MAIN RESULTS: A total of 25 trials representing
      31 control-intervention comparisons were included in the review randomising 5572
      children. Most of the participants were inadequately controlled on current ICS
      dose. We assessed the addition of LABA to the same dose of ICS and to an
      increased dose of ICS:(1) The addition of LABA to ICS was compared to same dose
      ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The
      mean age of participants was 10 years and males accounted for 64% of the study
      populations. The mean FEV(1) at baseline was 80% of predicted or above in 10
      studies; FEV(1) 61% to 79% of predicted in eight studies; and unreported in the
      remaining study. Participants were inadequately controlled before randomisation
      in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was
      not associated with a significant reduction in exacerbations requiring oral
      steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone,
      there was a significantly greater improvement in FEV1 with the addition of LABA
      (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant
      group differences in symptom-free days, hospital admission, quality of life, use
      of reliever medication, and adverse events. Withdrawals occurred significantly
      less frequently with the addition of LABA.(2) A total of seven studies assessed
      the addition of LABA to ICS therapy compared with an increased dose of ICS
      randomising 1021 children. The mean age of participants was 8 years with 67% of
      males. The baseline mean FEV(1) was 80% of predicted or above in 2 of the 3
      studies reporting this characteristic. All trials enrolled participants who were
      inadequately controlled on a baseline dose equivalent to 400 mcg/day of
      beclomethasone or less. There was no group significant difference in the risk of
      an exacerbation requiring oral steroids with the combination of LABA and ICS
      compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The
      increased risk of hospital admission with combination therapy was also not
      statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose
      ICS, use of LABA was associated with a significantly greater improvement in
      morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF
      L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were
      insufficient data to aggregate data on FEV(1), symptoms, rescue reliever use, and
      quality of life. There was no statistically significant difference in the overall
      risk of all cause withdrawals (five studies; RR 0.71; 95% CI 0.42 to 1.20. There
      was no group difference in the risk of overall adverse effects detected. Short
      term growth was significantly greater in children treated with combination
      therapy compared to double dose ICS (two studies: MD 1.2 cm/year; 95% CI 0.72 to
      1.7). AUTHORS' CONCLUSIONS: In children with persistent asthma, the addition of
      LABA to ICS was not associated with a significant reduction in the rate of
      exacerbations requiring systemic steroids, but was superior for improving lung
      function compared to the same dose of ICS. Similarly, compared to a double dose
      ICS, the combination of LABA and ICS did not significantly increase the risk of
      exacerbations requiring oral steroids, but was associated with a significantly
      greater improvement in PEF and growth. The possibility of an increased risk of
      rescue oral steroids and hospital admission with LABA therapy needs to be further
      examined.

PMID- 19588448
TI  - Antidepressants versus placebo for depression in primary care.
AB  - BACKGROUND: Concern has been expressed about the relevance of secondary care
      studies to primary care patients specifically about the effectiveness of
      antidepressant medication. There is a need to review the evidence of only those
      studies that have been conducted comparing antidepressant efficacy with placebo
      in primary care-based samples. OBJECTIVES: To determine the efficacy and
      tolerability of antidepressants in patients (under the age of 65 years) with
      depression in primary care. SEARCH STRATEGY: All searches were conducted in
      September 2007.The Cochrane Depression, Anxiety and Neurosis Group (CCDAN)
      Controlled Trials Register was searched, together with a supplementary search of
      MEDLINE, PsycINFO, EMBASE, LILACS, CINAHL and PSYNDEX. Abstracts of all possible
      studies for inclusion were assessed independently by two reviewers. Further
      trials were sought through searching the reference lists of studies initially
      identified and by scrutinising other relevant review papers. Selected authors and
      experts were also contacted. SELECTION CRITERIA: Studies were selected if they
      were randomised controlled trials of tricyclic antidepressants (TCAs) or
      selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults. Older
      patients (over 65 years) were excluded. Patients had to be recruited from a
      primary care setting. For continuous outcomes the Hamilton Depression scale of
      the Montgomery Asberg Scale was requred. DATA COLLECTION AND ANALYSIS: Data were
      extracted using data extraction forms by two reviewers independently, with
      disagreements resolved by discussion. A similar process was used for the validity
      assessment. Pooling of results was done using Review Manager 5. The primary
      outcome was depression reduction, based on a dichotomous measure of clinical
      response, using relative risk (RR), and on a continuous measure of depression
      symptoms, using the mean difference (MD), with 95% confidence intervals (CI).
      MAIN RESULTS: There were fourteen studies (16 comparisons) with extractable data
      included in the review, of which ten studies examined TCAs, two examined SSRIs
      and two included both classes, all compared with placebo. The number of
      participants in the intervention groups was 1364 and in the placebo groups 919.
      Nearly all studies were of short duration, typically 6-8 weeks. Pooled estimates
      of efficacy data showed an RR of 1.24, 95% CI 1.11-1.38 in favour of TCAs against
      placebo. For SSRIs this was 1.28, 95% CI 1.15 to 1.43.. The numbers needed to
      treat (NNT) for TCAs ranged from 7 to 16 {median NNT 9} patient expected event
      rate ranged from 63% to 26% respectively) and for SSRIs from 7 to 8 {median NNT
      7} (patient expected event rate ranged from 48% to 42% respectively) . The
      numbers needed to harm (NNH for withdrawal due to side effects) ranged from 4 to
      30 for TCAs (excluding three studies with no harmful events leading to
      withdrawal) and 20 to 90 for SSRIs. AUTHORS' CONCLUSIONS: Both TCAs and SSRIs are
      effective for depression treated in primary care.

PMID- 19588449
TI  - Methods to increase response to postal and electronic questionnaires.
AB  - BACKGROUND: Postal and electronic questionnaires are widely used for data
      collection in epidemiological studies but non-response reduces the effective
      sample size and can introduce bias. Finding ways to increase response to postal
      and electronic questionnaires would improve the quality of health research.
      OBJECTIVES: To identify effective strategies to increase response to postal and
      electronic questionnaires. SEARCH STRATEGY: We searched 14 electronic databases
      to February 2008 and manually searched the reference lists of relevant trials and
      reviews, and all issues of two journals. We contacted the authors of all trials
      or reviews to ask about unpublished trials. Where necessary, we also contacted
      authors to confirm methods of allocation used and to clarify results presented.
      We assessed the eligibility of each trial using pre-defined criteria. SELECTION
      CRITERIA: Randomised controlled trials of methods to increase response to postal
      or electronic questionnaires. DATA COLLECTION AND ANALYSIS: We extracted data on
      the trial participants, the intervention, the number randomised to intervention
      and comparison groups and allocation concealment. For each strategy, we estimated
      pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects
      model. We assessed evidence for selection bias using Egger's weighted regression
      method and Begg's rank correlation test and funnel plot. We assessed
      heterogeneity among trial odds ratios using a Chi(2) test and the degree of
      inconsistency between trial results was quantified using the I(2) statistic. MAIN
      RESULTS: PostalWe found 481 eligible trials. The trials evaluated 110 different
      ways of increasing response to postal questionnaires. We found substantial
      heterogeneity among trial results in half of the strategies. The odds of response
      were at least doubled using monetary incentives (odds ratio 1.87; 95% CI 1.73 to
      2.04; heterogeneity P < 0.00001, I(2) = 84%), recorded delivery (1.76; 95% CI
      1.43 to 2.18; P = 0.0001, I(2) = 71%), a teaser on the envelope - e.g. a comment
      suggesting to participants that they may benefit if they open it (3.08; 95% CI
      1.27 to 7.44) and a more interesting questionnaire topic (2.00; 95% CI 1.32 to
      3.04; P = 0.06, I(2) = 80%). The odds of response were substantially higher with
      pre-notification (1.45; 95% CI 1.29 to 1.63; P < 0.00001, I(2) = 89%), follow-up
      contact (1.35; 95% CI 1.18 to 1.55; P < 0.00001, I(2) = 76%), unconditional
      incentives (1.61; 1.36 to 1.89; P < 0.00001, I(2) = 88%), shorter questionnaires
      (1.64; 95% CI 1.43 to 1.87; P < 0.00001, I(2) = 91%), providing a second copy of
      the questionnaire at follow up (1.46; 95% CI 1.13 to 1.90; P < 0.00001, I(2) =
      82%), mentioning an obligation to respond (1.61; 95% CI 1.16 to 2.22; P = 0.98,
      I(2) = 0%) and university sponsorship (1.32; 95% CI 1.13 to 1.54; P < 0.00001,
      I(2) = 83%). The odds of response were also increased with non-monetary
      incentives (1.15; 95% CI 1.08 to 1.22; P < 0.00001, I(2) = 79%), personalised
      questionnaires (1.14; 95% CI 1.07 to 1.22; P < 0.00001, I(2) = 63%), use of hand
      written addresses (1.25; 95% CI 1.08 to 1.45; P = 0.32, I(2) = 14%), use of
      stamped return envelopes as opposed to franked return envelopes (1.24; 95% CI
      1.14 to 1.35; P < 0.00001, I(2) = 69%), an assurance of confidentiality (1.33;
      95% CI 1.24 to 1.42) and first class outward mailing (1.11; 95% CI 1.02 to 1.21;
      P = 0.78, I(2) = 0%). The odds of response were reduced when the questionnaire
      included questions of a sensitive nature (0.94; 95% CI 0.88 to 1.00; P = 0.51,
      I(2) = 0%).ElectronicWe found 32 eligible trials. The trials evaluated 27
      different ways of increasing response to electronic questionnaires. We found
      substantial heterogeneity among trial results in half of the strategies. The odds
      of response were increased by more than a half using non-monetary incentives
      (1.72; 95% CI 1.09 to 2.72; heterogeneity P < 0.00001, I(2) = 95%), shorter e
      questionnaires (1.73; 1.40 to 2.13; P = 0.08, I(2) = 68%), including a statement
      that others had responded (1.52; 95% CI 1.36 to 1.70), and a more interesting
      topic (1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third
      using a lottery with immediate notification of results (1.37; 95% CI 1.13 to
      1.65), an offer of survey results (1.36; 95% CI 1.15 to 1.61), and using a white
      background (1.31; 95% CI 1.10 to 1.56). The odds of response were also increased
      with personalised e-questionnaires (1.24; 95% CI 1.17 to 1.32; P = 0.07, I(2) =
      41%), using a simple header (1.23; 95% CI 1.03 to 1.48), using textual
      representation of response categories (1.19; 95% CI 1.05 to 1.36), and giving a
      deadline (1.18; 95% CI 1.03 to 1.34). The odds of response tripled when a picture
      was included in an e-mail (3.05; 95% CI 1.84 to 5.06; P = 0.27, I(2) = 19%). The
      odds of response were reduced when "Survey" was mentioned in the e-mail subject
      line (0.81; 95% CI 0.67 to 0.97; P = 0.33, I(2) = 0%), and when the e-mail
      included a male signature (0.55; 95% CI 0.38 to 0.80; P = 0.96, I(2) = 0%).
      AUTHORS' CONCLUSIONS: Health researchers using postal and electronic
      questionnaires can increase response using the strategies shown to be effective
      in this systematic review.

PMID- 19588450
TI  - Measuring SPIO and Gd contrast agent magnetization using 3 T MRI.
AB  - Traditional methods of measuring magnetization in magnetic fluid samples, such as
      vibrating sample magnetometry (VSM), are typically limited to maximum field
      strengths of about 1 T. This work demonstrates the ability of MRI to measure the
      magnetization associated with two commercial MRI contrast agents at 3 T by
      comparing analytical solutions to experimental imaging results for the field
      pattern associated with agents in cylindrical vials. The results of the VSM and
      fitted MRI data match closely. The method represents an improvement over VSM
      measurements since results are attainable at imaging field strengths. The agents
      investigated are Feridex, a superparamagnetic iron oxide suspension used
      primarily for liver imaging, and Magnevist, a paramagnetic, gadolinium-based
      compound used for tumors, inflammation and vascular lesions. MR imaging of the
      agents took place in sealed cylindrical vials in the presence of a surrounding
      volume of deionized water where the effects of the contrast agents had a
      measurable effect on the water's magnetization in the vicinity of the compartment
      of contrast agent. A pair of phase images were used to reconstruct a B(0)
      fieldmap. The resultant B(0) maps in the water region, corrected for shimming and
      container edge effects, were used to predict the agent's magnetization at 3 T.
      The results were compared with the results from VSM measurements up to 1.2 T and
      close correlation was observed. The technique should be of interest to those
      seeking quantification of the magnetization associated with magnetic suspensions
      beyond the traditional scope of VSM. The magnetization needs to be sufficiently
      strong (M(s) >or= 50 Am(2)/kg Fe for Feridex and X(m) >or=5 x 10(-5) m(3)/kg Gd
      for Magnevist) for a measurable dipole field in the surrounding water. For this
      reason, the technique is mostly suitable for undiluted agents.

PMID- 19588451
TI  - Multilevel mixture cure models with random effects.
AB  - This paper extends the multilevel survival model by allowing the existence of
      cured fraction in the model. Random effects induced by the multilevel clustering
      structure are specified in the linear predictors in both hazard function and
      cured probability parts. Adopting the generalized linear mixed model (GLMM)
      approach to formulate the problem, parameter estimation is achieved by maximizing
      a best linear unbiased prediction (BLUP) type log-likelihood at the initial step
      of estimation, and is then extended to obtain residual maximum likelihood (REML)
      estimators of the variance component. The proposed multilevel mixture cure model
      is applied to analyze the (i) child survival study data with multilevel
      clustering and (ii) chronic granulomatous disease (CGD) data on recurrent
      infections as illustrations. A simulation study is carried out to evaluate the
      performance of the REML estimators and assess the accuracy of the standard error
      estimates.

PMID- 19588452
TI  - The concordance index C and the Mann-Whitney parameter Pr(X>Y) with randomly
      censored data.
AB  - Harrell's c-index or concordance C has been widely used as a measure of
      separation of two survival distributions. In the absence of censored data, the c
      index estimates the Mann-Whitney parameter Pr(X>Y), which has been repeatedly
      utilized in various statistical contexts. In the presence of randomly censored
      data, the c-index no longer estimates Pr(X>Y); rather, a parameter that involves
      the underlying censoring distributions. This is in contrast to Efron's maximum
      likelihood estimator of the Mann-Whitney parameter, which is recommended in the
      setting of random censorship.

PMID- 19588453
TI  - Analysis of misclassified correlated binary data using a multivariate probit
      model when covariates are subject to measurement error.
AB  - A multivariate probit model for correlated binary responses given the predictors
      of interest has been considered. Some of the responses are subject to
      classification errors and hence are not directly observable. Also measurements on
      some of the predictors are not available; instead the measurements on its
      surrogate are available. However, the conditional distribution of the
      unobservable predictors given the surrogate is completely specified. Models are
      proposed taking into account either or both of these sources of errors.
      Likelihood-based methodologies are proposed to fit these models. To ascertain the
      effect of ignoring classification errors and/or measurement error on the
      estimates of the regression and correlation parameters, a sensitivity study is
      carried out through simulation. Finally, the proposed methodology is illustrated
      through an example.

PMID- 19588454
TI  - Complementary log-log regression for the estimation of covariate-adjusted
      prevalence ratios in the analysis of data from cross-sectional studies.
AB  - We assessed complementary log-log (CLL) regression as an alternative statistical
      model for estimating multivariable-adjusted prevalence ratios (PR) and their
      confidence intervals. Using the delta method, we derived an expression for
      approximating the variance of the PR estimated using CLL regression. Then, using
      simulated data, we examined the performance of CLL regression in terms of the
      accuracy of the PR estimates, the width of the confidence intervals, and the
      empirical coverage probability, and compared it with results obtained from log
      binomial regression and stratified Mantel-Haenszel analysis. Within the range of
      values of our simulated data, CLL regression performed well, with only slight
      bias of point estimates of the PR and good confidence interval coverage. In
      addition, and importantly, the computational algorithm did not have the
      convergence problems occasionally exhibited by log-binomial regression. The
      technique is easy to implement in SAS (SAS Institute, Cary, NC), and it does not
      have the theoretical and practical issues associated with competing approaches.
      CLL regression is an alternative method of binomial regression that warrants
      further assessment.

PMID- 19588455
TI  - Estimation of the ROC curve under verification bias.
AB  - The ROC (receiver operating characteristic) curve is the most commonly used
      statistical tool for describing the discriminatory accuracy of a diagnostic test.
      Classical estimation of the ROC curve relies on data from a simple random sample
      from the target population. In practice, estimation is often complicated due to
      not all subjects undergoing a definitive assessment of disease status
      (verification). Estimation of the ROC curve based on data only from subjects with
      verified disease status may be badly biased. In this work we investigate the
      properties of the doubly robust (DR) method for estimating the ROC curve under
      verification bias originally developed by Rotnitzky, Faraggi and Schisterman
      (2006) for estimating the area under the ROC curve. The DR method can be applied
      for continuous scaled tests and allows for a non-ignorable process of selection
      to verification. We develop the estimator's asymptotic distribution and examine
      its finite sample properties via a simulation study. We exemplify the DR
      procedure for estimation of ROC curves with data collected on patients undergoing
      electron beam computer tomography, a diagnostic test for calcification of the
      arteries.

PMID- 19588456
TI  - Highest density difference region estimation with application to flow cytometric
      data.
AB  - Motivated by the needs of scientists using flow cytometry, we study the problem
      of estimating the region where two multivariate samples differ in density. We
      call this problem highest density difference region estimation and recognise it
      as a two-sample analogue of highest density region or excess set estimation. Flow
      cytometry samples are typically in the order of 10,000 and 100,000 and with
      dimension ranging from about 3 to 20. The industry standard for the problem being
      studied is called Frequency Difference Gating, due to Roederer and Hardy (2001).
      After couching the problem in a formal statistical framework we devise an
      alternative estimator that draws upon recent statistical developments such as
      patient rule induction methods. Improved performance is illustrated in
      simulations. While motivated by flow cytometry, the methodology is suitable for
      general multivariate random samples where density difference regions are of
      interest.

PMID- 19588457
TI  - Rapid analysis of serotonin and propranolol using miniaturized CE with deep-UV
      fluorescence detector.
AB  - The design and construction of a miniaturized CE system has been developed for
      the analysis of clinically important compounds; serotonin and rac-propranolol.
      Chiral separation of rac-propranolol was investigated by using native and
      derivatized CDs at varios pH levels (e.g. 2.5, 4.0, 6.0, 9.0). Confocal
      fluorescence microscopy was used for the native direct detection of target
      compounds. Analysis time obtained under the optimum separation conditions was 84
      s. LOD and LOQ values of serotonin were found as low as 22 and 72.6 fg/microL
      while these limits were 44 and 145.2 fg/microL for popranolol enantiomers,
      respectively. LOD and LOQ values were found to be the lowest limits reported
      before. The calibration curves were linear in the concentration range of 40-1500
      fg/microL with the determination coefficients between 0.9994 (+/-0.01) and 0.9997
      (+/-0.02).

PMID- 19588458
TI  - Microchip electrophoresis in low-temperature co-fired ceramics technology with
      contactless conductivity measurement.
AB  - In this paper a novel micromachined contactless conductivity CE device produced
      in low temperature co-fired ceramics (LTCC) is introduced. The application of
      LTCC multilayer technology provides a promising method for the contactless
      detection of conductive compounds because of its increased dielectric constant
      compared with glass or plastics. The capacitive coupling of the excitation signal
      into the microchannel across the LTCC substrate is improved, resulting in better
      detection sensitivity. Two silver electrodes located externally at opposite sides
      at the end of the separation channel act as detector. Impedance variations in the
      channel are measured without galvanic contact between electrodes and fluid.
      Inorganic ions are separated in less than 1 min with this novel ceramic device.
      The limit of detection is 10 microM for potassium.

PMID- 19588459
TI  - Components of variance in transcriptomics based on electrophoretic separation of
      cDNA fragments (cDNA-AFLP).
AB  - The sources of variance and errors in transcriptomics based on the
      electrophoretic separation of amplified cDNA fragments were investigated using
      cDNA-amplified fragment length polymorphism (AFLP). Transcriptome profiles of the
      plant-pathogenic fungus Verticillium longisporum were generated by a standard
      cDNA-AFLP protocol followed by electrophoretic separation of amplified DNA
      fragments in flatbed polyacrylamide gels with fluorescence detection as well as
      by capillary electrophoresis (DNA sequencer). The total variance was partitioned
      into contributions of cDNA synthesis, adapter ligation, preamplification,
      amplification, and electrophoresis. Parameters of computer-aided peak recognition
      and matching were investigated and strategies improving matching success based on
      double passage with different signal intensity thresholds were developed. The
      overall quality of data was similar for cDNA-AFLP and microarray hybridization.
      Variance of cDNA-AFLP was independent of signal intensity, whereas microarray
      data showed higher variance for low-intensity signals. Capillary electrophoresis
      significantly reduced the number of wrongly matched and unmatched signals as
      compared with flatbed gels. These results are also likely to apply to related
      electrophoresis-based transcriptome analysis techniques such as mRNA differential
      display.

PMID- 19588460
TI  - Inequality of opportunities in health in France: a first pass.
AB  - This article analyses the role played by childhood circumstances, especially
      social and family background in explaining health status among older adults. We
      explore the hypothesis of an intergenerational transmission of health
      inequalities using the French part of SHARE. As the impact of both social
      background and parents' health on health status in adulthood represents
      circumstances independent of individual responsibility, this study allows us
      testing the existence in France of inequalities of opportunity in health related
      to family and social background. Empirically, our study relies on tests of
      stochastic dominance at first order and multivariate regressions, supplemented by
      a counterfactual analysis to evaluate the long-lasting impact of childhood
      conditions on inequality in health. Allocating the best circumstances in both
      parents' socioeconomic status and parents' health reduces inequality in health by
      an impressive 57% using the Gini coefficient. The mother's social status has a
      direct effect on the health of her offspring. By contrast, the effect on
      descendant's health from their father's social status is indirect only, which
      goes through the descendant's social status as an adult. There is also a strong
      effect of the father vital status on health in adulthood, revealing a selection
      effect.

PMID- 19588465
TI  - Colorimetric protein sensing by controlled assembly of gold nanoparticles
      functionalized with synthetic receptors.
AB  - A novel strategy is described for the colorimetric sensing of proteins, based on
      polypeptide-functionalized gold nanoparticles. Recognition is accomplished using
      a polypeptide sensor scaffold designed to specifically bind to the model analyte,
      human carbonic anhydrase II (HCAII). The extent of particle aggregation, induced
      by the Zn(2+)-triggered dimerization and folding of a second polypeptide also
      present on the surface of the gold nanoparticle, gives a readily detectable
      colorimetric shift that is dependent on the concentration of the target protein.
      In the absence of HCAII, particle aggregation results in a major redshift of the
      plasmon peak, whereas analyte binding prevented the formation of dense
      aggregates, significantly reducing the magnitude of the redshift. The versatility
      of the technique is demonstrated using a second model system based on the
      recognition of a peptide sequence from the tobacco mosaic virus coat protein
      (TMVP) by a recombinant antibody fragment (Fab57P). Concentrations down to
      approximately 10 nM and approximately 25 nM are detected for HCAII and Fab57P,
      respectively. This strategy is proposed as a generic platform for robust and
      specific protein analysis that can be further developed to monitor a wide range
      of target proteins.

PMID- 19588464
TI  - Contactless electrofunctionalization of a single pore.
AB  - Customized pores are smart components that find challenging applications in a
      variety of fields including purification membranes and biosensing systems. The
      incorporation of recognition probes within pores is therefore a challenge, due to
      the technical difficulty of delimiting the area functionalized and obtaining the
      localized, specific chemical modification of pore walls. An innovative approach,
      named contactless electrofunctionalization (CLEF), is presented to overcome this
      problem. CLEF allows easy, one-step modification of the inner surface of a pore
      etched in a dielectric membrane. The pore wall is coated under the influence of
      an electric field created by the application of a voltage between two electrodes,
      located near but not in contact with the pore openings. This specific
      localization of the deposited material within the pore is extremely rapid.
      Coatings were reliably and reproducibly obtained using polypyrrole co-polymers
      bearing oligonucleotides, demonstrating that this technology has a promising
      future in the design of biosensors. Moreover, the versatility of this process
      allows the deposition of various electroactive entities such as iridium oxide and
      therefore indicates a strong potential for diverse applications involving porous
      materials.

PMID- 19588466
TI  - Pulsations in the umbilical vein during labor are associated with increased risk
      of operative delivery for fetal distress.
AB  - OBJECTIVES: Under physiological conditions the blood flow velocity waveform in
      the umbilical vein (UV) has an even non-pulsating pattern. Pulsations in the UV
      have been described in human fetuses exposed to chronic hypoxia and heart
      failure. Current techniques for fetal surveillance during labor and delivery
      involve a risk of both over- and underestimation of fetal hypoxia. We aimed to
      examine whether pulsations in the UV appear in the human fetus during suspected
      intrapartum hypoxia, and if so whether they are associated with increased risk of
      operative delivery for fetal distress (ODFD). METHODS: This was a prospective
      double blind study including 52 normal pregnancies. A Doppler examination of the
      UV was performed on 26 fetuses with pathological and 26 fetuses with normal
      cardiotocography (CTG) during labor. Presence or absence of pulsations in the UV
      were noted and related to perinatal outcome. RESULTS: Pulsations in the UV were
      seen in eight (30.8%) of the fetuses with pathological CTG, of which six (75%)
      underwent ODFD. No pulsations were seen in the other 18 (69.2%) fetuses with
      pathological CTG and these were all delivered without ODFD. No pulsations were
      seen in the UV in the fetuses with normal CTG and these were all delivered
      without ODFD. Among the fetuses with pathological CTG, there was an increased
      risk of ODFD in fetuses with vs. those without pulsations in the UV (P < 0.0001).
      CONCLUSIONS: Pulsations in the UV can be observed in human fetuses during
      suspected intrapartum hypoxia and these pulsations are associated with an
      increased risk of ODFD. Doppler examination of the UV might give important
      additional information on fetal condition during labor and delivery.

PMID- 19588469
TI  - The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2(High)
      receptors.
AB  - Dopaminergic stabilizers are recognized as compounds that can either enhance or
      antagonize dopamine (DA)-dependent behaviors depending on the prevailing
      dopaminergic tone. The dopaminergic stabilizer ASP2314 is being tested clinically
      and has been reported to have antipsychotic effects in a clinical trial as an add
      on medication. To elucidate the mechanisms of action of this dopaminergic
      stabilizer, its potency on the functional dopamine D2(High) receptors was
      examined. In competition with D2 receptors selectively labeled by
      [3H]domperidone, ASP2314 had a dissociation constant, Ki(High), of 1.62 microM
      for D2(High) in human cloned D2Long receptors and 0.83 muM for rat homogenized
      striata. Using the D2 agonist ligand [3H](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H
      naphtho[1,2-b][1,4]oxazin-9-ol ((+)PHNO), ASP2314 had a high-affinity Ki of 32 nM
      for D2(High) for rat homogenized striata. ASP2314 stimulated the incorporation of
      [35S]GTP-gamma-S into rat striata by 50% at 43 nM, and into the cloned D2Long
      membranes by 50% at 3.2 microM (compared to 100% stimulation by 10 microM
      dopamine). With similar concentrations of ASP2314 inhibiting the binding of
      ligands at D2(High) and stimulating [35S]GTP-gamma-S incorporation, the data
      indicate that the dopaminergic stabilizing action of ASP2314 may be related to
      the selectivity for the D2(high) state of the D2 receptor.

PMID- 19588468
TI  - Association and gene-gene interaction of SLC6A4 and ITGB3 in autism.
AB  - Autism is a heritable neurodevelopmental disorder with substantial genetic
      heterogeneity. Studies point to possible links between autism and two serotonin
      related genes: SLC6A4 and ITGB3 with a sex-specific genetic effect and
      interaction between the genes. Despite positive findings, inconsistent results
      have complicated interpretation. This study seeks to validate and clarify
      previous findings in an independent dataset taking into account sex, family
      history (FH) and gene-gene effects. Family-based association analysis was
      performed within each gene. Gene-gene interactions were tested using extended
      multifactor dimensionality reduction (EMDR) and MDR-phenomics (MDR-P) using sex
      of affecteds and FH as covariates. No significant associations with individual
      SNPs were found in the datasets stratified by sex, but associations did emerge
      when we stratified by family history. While not significant in the overall
      dataset, nominally significant association was identified at RS2066713 (P =
      0.006) within SLC6A4 in family-history negative (FH-) families, at RS2066713 (P =
      0.038) in family-history positive (FH+) families but with the opposite risk
      allele as in the FH- families. For ITGB3, nominally significant association was
      identified at RS3809865 overall (P = 0.040) and within FH+ families (P = 0.031).
      However, none of the associations survived the multiple testing correction. MDR-P
      confirmed gene-gene effects using sex of affecteds (P = 0.023) and family history
      (P = 0.014, survived the multiple testing corrections) as covariates. Our results
      indicate the extensive heterogeneity within these two genes among families. The
      potential interaction between SLC6A4 and ITGB3 may be clarified using family
      history as an indicator of genetic architecture, illustrating the importance of
      covariates as markers of heterogeneity in genetic analyses.

PMID- 19588467
TI  - Association of reading disabilities with regions marked by acetylated H3 histones
      in KIAA0319.
AB  - Reading disabilities (RDs) have been associated with chromosome 6p with recent
      studies pointing to two genes, DCDC2 and KIAA0319. In this study, markers across
      the 6p region were tested for association with RD. Our strongest findings were
      for association with markers in KIAA0319, although with the opposite alleles
      compared with a previous study. We also found association with markers in VMP,
      but not with DCDC2. Current evidence indicates that differential regulation of
      KIAA0319 and DCDC2 contributes to RD, thus we used chromatin immunoprecipitation
      coupled with genomic tiling arrays (ChIP-chip) to map acetylated histones, a
      molecular marker for regulatory elements, across a 500 kb genomic region covering
      the RD locus on 6p. This approach identified several regions marked by acetylated
      histones that mapped near associated markers, including intron 7 of DCDC2 and the
      5' region of KIAA0319. The latter is located within the 70 kb region previously
      associated with differential expression of KIAA0319. Interestingly, five markers
      associated with RD in independent studies were also located within the 2.7 kb
      acetylated region, and six additional associated markers, including the most
      significant one in this study, were located within a 22 kb haplotype block that
      encompassed this region. Our data indicates that this putative regulatory region
      is a likely site of genetic variation contributing to RD in our sample, further
      narrowing the candidate region.

PMID- 19588470
TI  - Role of GABA transporter 3 in GABAergic synaptic transmission at striatal output
      neurons.
AB  - Striatal GABAergic signaling has been shown to be essential for basal ganglia
      output and proper motor performance. In the mouse neostriatum GABA transporter 1
      (GAT-1) was previously found to assist in the clearance of GABA from the
      extracellular space and influence both phasic and tonic GABAergic inhibition of
      medium-sized striatal output neurons (SONs). It currently remains unknown whether
      GAT subtypes other than GAT-1 participate in the modulation of GABAergic
      transmission in this brain structure. In this study, we aimed at assessing the
      role of GAT-3 in the mouse neostriatum. To this end, we recorded GABAergic
      inhibitory postsynaptic currents (IPSCs) from SONs in brain slices at different
      developmental stages (postnatal days (P) 7-9, 12-14, and 28-34) using the whole
      cell patch-clamp technique. When applied under control conditions, SNAP-5114 (40
      microM), a specific GAT-3 blocker, did not affect miniature or evoked IPSCs
      (m/eIPSCs) and produced no significant effect on tonic GABAA receptor-mediated
      conductances in SONs. However, in the presence of NO-711 (10 microM), a specific
      GAT-1 blocker, SNAP-5114 reduced mIPSC frequencies without affecting mIPSC
      amplitudes or kinetics. In addition, SNAP-5114 reduced the mean amplitude of
      eIPSCs and increased the paired-pulse ratio. These effects were entirely
      abolished by CGP55845 (1 microM), a specific GABAB receptor blocker, indicating
      that they were mediated by presynaptic GABAB receptors. Similar results were
      obtained from all age groups. We conclude that GAT-3 is functionally expressed in
      the mouse neostriatum. Whereas an acute block of GAT-3 under resting conditions
      is fully compensated for by GAT-1, GAT-3 might provide an additional uptake
      capacity when neuronal activity and GABA release are increased.

PMID- 19588471
TI  - Glutamate agonist LY404,039 for treating schizophrenia has affinity for the
      dopamine D2(High) receptor.
AB  - The glutamate agonist LY404,039 has been used to treat schizophrenia. Because all
      currently used antipsychotics act on dopamine receptors, it was decided to
      examine whether this glutamate agonist also had an affinity for dopamine D2
      receptors in vitro. The present data show that LY404,039 inhibited the binding of
      [3H]domperidone and [3H]+PHNO by 15.5 +/- 1.5% to the high-affinity state,
      D2(High), of cloned dopamine D2(Long) receptors and rat striatal tissue with
      dissociation constants of between 8.2 and 12.6 nM. This high-affinity component
      of LY404,039 on the binding of [3H]domperidone was inhibited by the presence of
      guanine nucleotide, indicating an agonist action of the drug at D2(High).
      LY404,039 also stimulated the incorporation of [35S]GTP-gamma-S into D2(Long)
      receptors (EC50% = 80 +/- 15 nM) over the same range of concentrations as
      occurred for the inhibition of [3H]domperidone by LY404,039 at D2(High)
      (IC50%(High) = 50 +/- 10 nM). A possible clinical antipsychotic action of
      LY404,039 may depend on the combined stimulation of glutamate receptors and a
      partial dopamine agonist action that would interfere with neurotransmission at
      D2(High) receptors.

PMID- 19588472
TI  - Ex vivo and in vivo evaluation of [18F]PR04.MZ in rodents: a selective dopamine
      transporter imaging agent.
AB  - N-4-Fluorobut-2-yn-1-yl-2beta-carbomethoxy-3beta-phenyltropane (PR04.MZ) has been
      developed as dopamine transporter (DAT) ligand for molecular imaging. It contains
      a terminally fluorinated, conformationally constrained nitrogen substituent that
      is well suited for the introduction of fluorine-18. The present report describes
      the pharmacological characterisation of [18F]PR04.MZ. The ligand shows an IC50
      value of 2 nM against human DAT, whereas the IC50 value against human serotonin
      transporter and human noradrenalin transporter are lower (110 nM and 22 nM,
      respectively). Furthermore, its ex vivo organ distribution, its binding profile
      in the rat brain and reversibility of binding were examined. A muPET study
      illuminates a fast kinetic profile and specific binding to rat DAT.

PMID- 19588473
TI  - A consistent dataset of kinetic solubilities for early-phase drug discovery.
AB  - Herein, we describe a new dataset of kinetic aqueous solubilities determined by
      nephelometry for 711 druglike compounds. The solubilities are reported in twelve
      classes ranging from <2 microg mL(-1) to >250 microg mL(-1). The measurements
      were designed to provide the appropriate data for applications in the early
      phases of drug discovery. Three class classification models (insoluble,
      moderately soluble, soluble) were built using the random forest algorithm and
      their performance for this dataset was analyzed.

PMID- 19588474
TI  - Selective oxidation of methanol to hydrogen over gold catalysts promoted by
      alkaline-earth-metal and lanthanum oxides.
AB  - A series of alumina-supported gold catalysts was investigated for the CO-free
      production of hydrogen by partial oxidation of methanol. The addition of alkaline
      earth metal oxide promoters resulted in a significant improvement of the
      catalytic performance. The methanol conversion was ca. 85 % with all studied
      catalyst materials, however, the selectivity for hydrogen increased from 15 % to
      51 % when going from the unpromoted to a BaO-promoted catalyst. The formation of
      the undesired byproducts CO, methane, and dimethyl ether was considerably reduced
      as well. The observed trend in catalyst performance follows the trend in
      increasing basicity of the studied promoter elements, indicating a chemical
      effect of the promoter material. Superior catalytic performance, in terms of H(2)
      and CO selectivity, was obtained with a Au/La(2)O(3) catalyst. At 300 degrees C
      the hydrogen selectivity reached 80 % with only 2 % CO formation, and the
      catalyst displayed a stable performance over at least 24 h on-stream.
      Furthermore, the formation of CO was found to be independent of the oxygen
      concentration in the feed. The commercial lanthanum oxide used in this study had
      a low specific surface area, which led to the formation of relative large gold
      particles. Therefore, the catalytic activity could be enhanced by decreasing the
      gold particle size through deposition on lanthanum oxide supported on high
      surface-area alumina.

PMID- 19588476
TI  - The search for infectious causes of human cancers: where and why (Nobel lecture).
AB  - Slightly more than 20% of the global cancer burden can currently be linked to
      infectious agents, including viruses, bacteria, and parasites. In this Review the
      reasons for their relatively late discovery are analyzed, and epidemiological
      observations that may point to an involvement of additional infectious agents in
      specific human cancers are highlighted. Emphasis is placed on hematopoietic
      malignancies, breast and colorectal cancers, as well as basal cell carcinomas of
      the skin and lung cancers in nonsmokers.

PMID- 19588475
TI  - Biotransformation on polymer-peptide conjugates: a versatile tool to trigger
      microstructure formation.

PMID- 19588477
TI  - Testing and improving the effectiveness of trap crops for management of the
      diamondback moth Plutella xylostella (L.): a laboratory-based study.
AB  - BACKGROUND: The aim of this study was to assess white mustard (Sinapis alba L.)
      as a trap crop for diamondback moth [Plutella xylostella (L.)] on cauliflower
      [Brassica oleracea (L.) var. Lateman]. Moth behaviour on these plants and the
      importance of plant age and size in maintaining pest preference for trap crop
      plants were also investigated. RESULTS: Three times as many eggs were laid on
      cauliflower plants that were unprotected than on plants protected by a trap crop
      of white mustard. Moths remained longer on the mustard plants as a result of a
      doubling in the mean duration of information-providing behaviours. Plant age had
      little effect on P. xylostella host preference. When plant age was constant,
      percentage oviposition on mustard was higher when these were larger (93%) than
      copresented cauliflower plants, compared with when they were smaller (68%).
      CONCLUSION: Trap cropping with white mustard may reduce the incidence of P.
      xylostella in cauliflower crops. The pest management benefits of trap crops may
      be maximised by using trap crop plants that are larger than the main crop plants,
      although relatively smaller trap crop plants may still be preferred as hosts for
      P. xylostella per se.

PMID- 19588478
TI  - Copper(I) cuboctahedral coordination cages: host-guest dependent redox activity.

PMID- 19588479
TI  - Selective synthesis of [12]cycloparaphenylene.

PMID- 19588480
TI  - Rationally engineered total biosynthesis of a synthetic analogue of a natural
      quinomycin depsipeptide in Escherichia coli.

PMID- 19588481
TI  - Learning of cross-sectional anatomy using clay models.
AB  - We incorporated clay modeling into gross anatomy and neuro-anatomy courses to
      help students understand cross-sectional anatomy. By making clay models, cutting
      them and comparing cut surfaces to CT and MR images, students learned how cross
      sectional two-dimensional images were created from three-dimensional structure of
      human organs. Most students in a clay modeling group responded positively to this
      approach, and their average score on CT examination was higher than that of a
      group that did not use clay models. Clay modeling appears to be a useful
      supplement to conventional anatomy or radiologic anatomy education. It can be
      applied to any part of human body, and its effectiveness will be greater when a
      more complicated understanding of cross-sectional anatomy is required.

PMID- 19588482
TI  - Permeation of urea through various polyurethane membranes.
AB  - BACKGROUND: Controlled-release systems using polymer membranes are very important
      in agriculture for labour-saving and effective delivery of pesticides and other
      agents. Polymer-coated granules are one of the most useful formulations, and a
      study of the factors for polymer design is necessary to achieve various release
      patterns. A permeation study using plain membranes was carried out in order to
      clarify parameters, and the results were compared with the release from polymer
      coated granules. RESULTS: The permeation coefficient of urea through a plain
      polyurethane membrane decreased significantly as the urethane and alkyl side
      chain content increased. The glass transition temperature and crosslink density
      of the polyurethanes hardly influenced its permeability. The release rate from
      polyurethane-coated granules was also reduced by alkyl side chains. However, it
      was faster than that through a plain membrane because of capsule expansion by
      continuous water penetration and structural changes in the membrane. CONCLUSION:
      The release rate of urea through a polyurethane plain membrane and from
      polyurethane-coated granules can be controlled by changing the chemical
      properties of the membrane. In addition, physical properties such as the glass
      transition temperature T(g) or crosslink density should be considered to assess
      the release profile from polyurethane-coated granules.

PMID- 19588484
TI  - Overexpression of Sp1 leads to p53-dependent apoptosis in cancer cells.
AB  - Numerous studies have documented that Sp1 expression level were elevated in
      various human cancers. However, the promoters of many pro-apoptotic genes have
      been found to contain the Sp1 binding elements and are activated by Sp1
      overexpression. To better understand the role and the mechanism of increased Sp1
      levels on apoptosis, we used adenovirus to ectopically express GFP-Sp1 protein in
      various cancer cell lines. First, in HeLa and A549 cells, we found that Sp1
      overexpression suppressed the cell growth and increased the detection of sub-G1
      fraction, caspase-3 cleavage, and annexin-V signal revealed that apoptosis
      occurred. Furthermore, when cells entered the mitotic stage, the cell apoptosis
      was induced by Sp1 overexpression through affecting mitotic chromatin packaging.
      We also verified that p53 protein was accumulated and activated the p53-dependent
      apoptotic pathways in the wild-type p53 cells but not in the p53-mutated or p53
      deleted cell lines when these cells were infected with adeno-GFP-Sp1 virus. In
      addition, A549 (p53(+/+)) cells could be protected from apoptosis under Sp1
      overexpression when p53 was knockdown by p53 shRNA. Finally, H1299 (p53(-/-))
      cell viability was significantly inhibited by adeno-GFP-Sp1 virus infection in
      the expression of p53. In conclusion, p53 was an essential factor for Sp1
      overexpression-induced apoptotic cell death in transforming cells.

PMID- 19588483
TI  - STAT3 activation contributes directly to Epstein-Barr virus-mediated invasiveness
      of nasopharyngeal cancer cells in vitro.
AB  - Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)-associated head and
      neck cancer prevalent in Asia. Although with reasons not fully understood, the
      intrinsic invasiveness of NPC is believed to be EBV-linked. Recently, EBV was
      found to induce STAT3 activation. Constitutive STAT3 activation correlated with
      advanced clinical staging in NPC. We hypothesized that STAT3 activation by EBV
      directly contributes to the intrinsic invasiveness of NPC cells. Phospho-STAT3
      Tyr705 was detected in high percentage of NPC tumors (7/10 cases). Using a paired
      NPC cell line model, HONE-1 and the EBV-infected counterpart, HONE-1-EBV, we
      found that HONE-1-EBV expressed a higher level of phospho-STAT3-Tyr705 and was
      approximately 11-fold more invasive than HONE-1. In HONE-1-EBV, STAT3 siRNA
      targeting inhibited both spontaneous and serum-induced invasion, as well as cell
      growth. Conversely, activation of STAT3 (by expressing an activated STAT3 mutant,
      namely STAT3C) in the parental HONE-1, mimicking EBV-induced STAT3 activation,
      significantly enhanced its invasiveness and proliferation, which was accompanied
      by increased expression of markers of mesenchymal status, proliferation and anti
      apoptosis. Our results demonstrated that EBV-induced STAT3 activation is
      responsible for NPC cell proliferation and invasion. This was further confirmed
      by a small molecule inhibitor of JAK/STAT3, JSI-124. JSI-124 inhibited STAT3
      activation in HONE-1-EBV, with subsequent growth inhibition, induction of PARP
      cleavage, abrogation of anchorage-independent growth and invasion. We found that
      EBV-independent activation of STAT3 by a growth factor, EGF, also contributed to
      NPC invasion. In conclusion, EBV-induced STAT3 activation directly contributes to
      the intrinsic invasiveness of NPC cells and STAT3 targeting may be beneficial in
      treating aggressive NPC.

PMID- 19588485
TI  - Repeated measures of serum glucose and insulin in relation to postmenopausal
      breast cancer.
AB  - Experimental and epidemiological evidence suggests that circulating glucose and
      insulin may play a role in breast carcinogenesis. However, few cohort studies
      have examined breast cancer risk in association with glucose and insulin levels,
      and studies to date have had only baseline measurements of exposure. We conducted
      a longitudinal study of postmenopausal breast cancer risk using the 6% random
      sample of women in the Women's Health Initiative clinical trials whose fasting
      blood samples, provided at baseline and at years 1, 3 and 6, were analyzed for
      glucose and insulin. In addition, a 1% sample of women in the observational
      study, who had glucose and insulin measured in fasting blood samples drawn at
      baseline and in year 3, were included in the analysis. We used Cox proportional
      hazards models to estimate hazard ratios and 95% confidence intervals for the
      association of baseline and follow-up measurements of serum glucose and insulin
      with breast cancer risk. All statistical tests were 2-sided. Among 5,450 women
      with baseline serum glucose and insulin values, 190 incident cases of breast
      cancer were ascertained over a median of 8.0 years of follow-up. The highest
      tertile of baseline insulin, relative to the lowest, was associated with a 2-fold
      increase in risk in the total population (multivariable hazard ratio 2.22, 95%
      confidence interval 1.39-3.53) and with a 3-fold increase in risk in women who
      were not enrolled in the intervention arm of any clinical trial (multivariable
      hazard ratio 3.15, 95% confidence interval 1.61-6.17). Glucose levels showed no
      association with risk. Analysis of the repeated measurements supported the
      results of the baseline analysis. These data suggest that elevated serum insulin
      levels may be a risk factor for postmenopausal breast cancer.

PMID- 19588486
TI  - Rectal cancer survival in the Nordic countries and Scotland.
AB  - The aim of this study was to present detailed population-based survival estimates
      for patients with a rectal adenocarcinoma, using cancer register data
      supplemented with clinical data. Based on cancer register data, differences in
      rectal cancer survival have been reported between countries in Europe. Variation
      in the distribution of stage at diagnosis, initial therapy including surgical
      technique, and comorbidity are possible explanatory factors. Adenocarcinomas in
      the rectum, diagnosed in 1997 and identified in the national cancer registries in
      the Nordic countries and Scotland were included. Age standardized 5-year relative
      survival and multiplicative regression models for the relative excess mortality
      were calculated. 3888 patients were included in the survival study. Men in
      Denmark, Finland and Iceland had lower 5-year relative survival and poorer stage
      distribution compared to Norway, Sweden and Scotland. Danish men had the highest
      rate of excess deaths in the first six months after diagnosis. Stage adjusted,
      the elevated relative excess mortality decreased and after six months the excess
      mortality rates were the same in all countries. The poor 5-year relative survival
      in Danish men was mainly due to a high excess rate of death during the first six
      months after diagnosis. The low survival in Finland and Iceland was not in
      accordance with other periods. For both countries this may be explained by random
      variation due to small numbers. The study emphasizes the need for high quality
      and detailed data in order to understand international survival differences, and
      cautions comparisons between large national samples and those of smaller areas.

PMID- 19588487
TI  - EGFRvIII-induced estrogen-independence, tamoxifen-resistance phenotype correlates
      with PgR expression and modulation of apoptotic molecules in breast cancer.
AB  - The tumor-specific, ligand-independent, constitutively active epidermal growth
      factor receptor (EGFR) variant, EGFRvIII, remains understudied in breast cancer.
      Here, we report that expression of EGFRvIII in the ErbB-2-overexpressing,
      estrogen-dependent MDA-MB-361 breast cancer cell line resulted in significant
      estrogen-independent tumor growth in ovariectomized, athymic nude mice in
      comparison to MDA-MB-361/wt cells. MDA-MB-361/vIII breast cancer cells maintained
      estrogen-induced tumor growth, but were tamoxifen-resistant in the presence of
      estrogen, while MDA-MB-361/wt cells had a significant reduction in tumor growth
      in the presence of estrogen and tamoxifen. Tamoxifen alone did not have a
      significant effect on EGFRvIII-mediated estrogen-independent tumor growth.
      Constitutive signaling from the EGFRvIII receptor resulted in an increased
      activation of both the Akt and MAPK pathways. Compared to estrogen-dependent,
      tamoxifen-sensitive MCF-7/vIII breast cancer cells, which had unchanged levels of
      ERalpha, but an increase in progesterone receptor (PgR) in comparison to MCF-7/wt
      cells, MDA-MB-361/vIII cells had a reduction in ERalpha expression as well as a
      more pronounced reduction in PgR compared with MDA-MB-361/wt cells. EGFRvIII
      expression was also significantly associated with an absence of PgR protein in
      invasive human breast cancer specimens. Alterations of proapoptotic proteins and
      antiapoptotic proteins were observed in EGFRvIII transfectants. In conclusion,
      constitutive signaling through EGFRvIII and its downstream effector proteins
      crosstalks with the ERalpha pathway, resulting in loss of PgR expression and
      alterations in the apoptotic pathway, which may result in the estrogen
      independent, tamoxifen-resistant phenotype conferred to EGFRvIII-expressing
      breast cancer cells.

PMID- 19588488
TI  - Kruppel-like factor 12 plays a significant role in poorly differentiated gastric
      cancer progression.
AB  - Gastric cancer is the second common malignant neoplasia in Japan, and its poorly
      differentiated form is a deadly disease. To identify novel candidate oncogenes
      contributing to its genesis, we examined copy-number alterations in 50 primary
      poorly differentiated gastric cancers using an array-based comparative genomic
      hybridization (array-CGH). Many genetic changes were identified, including a
      novel amplification of the 13q22 locus. Several genes are located in this locus,
      and selective knockdown of one for the Kruppel-like factor 12 (KLF12) induced
      significant growth-arrest in the HGC27 gastric cancer cell line. Microarray
      analysis also demonstrated that genes associated with cell proliferation were
      mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we
      introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines
      and found that overexpression significantly enhanced their invasive potential. In
      clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases
      (39%) when compared with normal gastric epithelium. Clinicopathological analysis
      further demonstrated a significant correlation between KLF12mRNA levels and tumor
      size (p = 0.038). These data suggest that the KLF12 gene plays an important role
      in poorly differentiated gastric cancer progression and is a potential target of
      therapeutic measures.

PMID- 19588490
TI  - Whole body regeneration in a colonial ascidian, Botrylloides violaceus.
AB  - Colonial ascidians are the only chordates to undergo whole body regeneration
      (WBR), the ability to form an entirely new individual from the peripheral
      vasculature. Here we describe WBR in Botrylloides violaceus, a colonial ascidian
      that reliably regenerates after ablation of all zooids and buds of young
      colonies. During early regeneration several buds develop within the tunic
      vasculature, but only one continues development into a complete zooid. We
      describe some of the first events of vascular budding leading to the vesicle
      stage with phase contrast microscopy, time-lapse video recording and detailed
      histological studies of regenerating colonies. The first conspicuous stage of
      vascular budding is when a single-layered sphere of cells becomes enclosed by
      vascular epithelium. We report the appearance of Piwi-positive cells in hemocytes
      surrounding the regenerates. We observed an increase of proliferating cell
      nuclear antigen (PCNA)-positive cells in circulatory hemocytes in late
      regenerates, and found double-labeled nuclear expression with Piwi in a subset of
      large circulatory cells. We rarely found Piwi or PCNA in differentiating tissues
      during vascular budding, suggesting that cells that form the epithelial tissues
      during budding and WBR originate mostly from circulatory hemocyte precursors. We
      propose that multiple stem cell types are circulating within B. violaceus and
      that they undergo proliferation in the peripheral vasculature before
      differentiating into epithelial tissues for all three germ layers during WBR.

PMID- 19588489
TI  - A case-control study of cutaneous squamous cell carcinoma among Caucasian organ
      transplant recipients: the role of antibodies against human papillomavirus and
      other risk factors.
AB  - A case-control study was conducted in 140 people with histology proven cutaneous
      squamous cell carcinoma (SCC) and 454 controls, nested within 2 cohorts of organ
      transplant recipients (OTR) recruited in London and Oxford between 2002 and 2006.
      All participants had a skin examination, completed a questionnaire and had serum
      tested for antibodies against the L1 antigen of 34 HPV types using Luminex
      technology. SCC was more common in men than women (odds ratio [OR] = 1.7, 95%
      confidence interval [CI]: 1.1-2.8, p = 0.02) and in people with susceptibility to
      burn easily (OR = 3.0, 95%CI: 1.9-4.8; p < 0.001). The risk increased with
      increasing age (p-trend < 0.001), increasing time since transplant (p-trend <
      0.001), increasing self-reported number of sunburns as a child (p-trend < 0.001)
      and with the presence of viral warts (p < 0.001). As expected, antibodies against
      HPV 16 were associated with a self-reported history of an abnormal cervical smear
      among women (OR 5.1, 95%CI: 2.6-10.2) and antibodies against HPV 6 were
      associated with a self-reported history of genital warts (OR 4.0, 95%CI: 2.2
      7.2). However, no clear associations between any of the HPV types examined
      (including cutaneous betaHPVs) and SCC were identified. For example, the
      seroprevalence of HPV 5 was 15% among cases and 9% among controls (p = 0.09) and
      the seroprevalence of HPV 8 was 23% among cases and 21% among controls (p = 0.6).
      Nor was seropositivity to multiple types associated with SCC. These serological
      data do not provide evidence for a role for HPV in the aetiology of cutaneous SCC
      among OTR in two UK-based populations.

PMID- 19588492
TI  - Functional versus operational menopause: reply to Herndon & Lacreuse.

PMID- 19588491
TI  - Intersex gonads in frogs: understanding the time course of natural development
      and role of endocrine disruptors.
AB  - The paucity of data on sexual development of anuran amphibians has played an
      important role in the recent controversy over atrazine exposure. Although some
      studies have demonstrated the presence of abnormal gonads in control treatments,
      others have not, leading to varying interpretations of the effects of atrazine
      exposure on sexual development. However, the timing of development varies among
      anuran amphibians such that, at any snapshot in time, different species may
      exhibit different stages of sexual differentiation. We examined three species
      representing each of the differentiation rates (Bufo americanus=retarded rate;
      Hyla versicolor=basic rate; Rana sphenocephala=accelerated rate), to examine the
      natural time course of sexual development along with the influence of atrazine
      exposure. For each species, exposure to atrazine (1, 3, 10, 30 parts per
      billion), 17-beta-estradiol or control water occurred throughout larval life.
      Gonad histology was performed at 3-week intervals during the larval period or at
      a juvenile stage to examine the proportion of males, females, underdeveloped
      testes, testicular oocytes (TO; testes with 0-30% oocytes), and ovotestes (OVTs;
      testes with>30% oocytes). Our results illustrate that a phase of intersex gonads
      (TO or OVT) is normal during R. sphenocephala sexual development, a species
      representing the accelerated differentiation rate. Further, intersex gonads were
      found in juvenile stages of B. americanus and H. versicolor, representing
      retarded and basic rates, respectively, suggesting that a phase of intersex may
      be common regardless of differentiation rate. Moreover, these data highlight the
      importance of longitudinal studies rather than snapshots in time.

PMID- 19588493
TI  - Analyses on hydrophobicity and attractiveness of all-atom distance-dependent
      potentials.
AB  - Accurate model evaluation is a crucial step in protein structure prediction. For
      this purpose, statistical potentials, which evaluate a model structure based on
      the observed atomic distance frequencies in comparison with those in reference
      states, have been widely used. The reference state is a virtual state where all
      of the atomic interactions are turned off, and it provides a standard to measure
      the observed frequencies. In this study, we examined seven all-atom distance
      dependent potentials with different reference states. As results, we observed
      that the variations of atom pair composition and those of distance distributions
      in the reference states produced systematic changes in the hydrophobic and
      attractive characteristics of the potentials. The performance evaluations with
      the CASP7 structures indicated that the preference of hydrophobic interactions
      improved the correlation between the energy and the GDT-TS score, but decreased
      the Z-score of the native structure. The attractiveness of potential improved
      both the correlation and Z-score for template-based modeling targets, but the
      benefit was smaller in free modeling targets. These results indicated that the
      performances of the potentials were more strongly influenced by their
      characteristics than by the accuracy of the definitions of the reference states.

PMID- 19588494
TI  - Differential oncogenic potential of geographically distinct Helicobacter pylori
      CagA isoforms in mice.
AB  - Infection with cagA-positive Helicobacter pylori is associated with gastric
      carcinoma. The cagA-encoded CagA protein is delivered into gastric epithelial
      cells and, upon tyrosine phosphorylation at the C-terminal EPIYA segments, binds
      and deregulates SHP-2 oncoprotein. On the basis of the differential alignment of
      the EPIYA segments, CagA can be subdivided into Western CagA, which is produced
      by H. pylori isolated in Western countries, and East Asian CagA, which is
      produced by H. pylori circulating in East Asian countries. Western CagA contains
      EPIYA-A, EPIYA-B and variable numbers of EPIYA-C segments, whereas East Asian
      CagA contains EPIYA-A, EPIYA-B and variable numbers of EPIYA-D segments. Upon
      tyrosine phosphorylation, EPIYA-C and EPIYA-D, respectively, serve as low
      affinity and high-affinity SHP-2-binding sites. We previously reported that
      systemic expression of East Asian CagA (CagA-ABDD) induces gastrointestinal and
      hematopoietic malignancies in mice. In this study, we generated transgenic mice
      that systemically express Western CagA (CagA-ABCCC), the levels of which are
      comparable to those in mice expressing East Asian CagA. The mice developed
      gastric epithelial hypertrophy and gastrointestinal tumors and also showed
      lymphoid abnormality but not myeloid abnormalities such as granulocytosis and
      myeloid leukemia found in mice carrying East Asian CagA. The incidence of tumors
      in mice expressing Western CagA was significantly lower than that in mice
      expressing East Asian CagA. Our results indicate that Western CagA is
      qualitatively less oncogenic than East Asian CagA. Differential oncogenic
      potential of geographically distinct CagA isoforms may contribute to the
      differential prevalence of gastric carcinoma between East Asian countries and
      Western countries.

PMID- 19588495
TI  - Detection of gastric carcinoma-associated MG7-Ag by serum immuno-PCR assay in a
      high-risk Chinese population, with implication for screening.
AB  - To evaluate gastric carcinoma-associated antigen, MG7-Ag, for detection of
      gastric cancer in a high-risk population, a population-based screening of gastric
      cancer was conducted in Linqu County, Shandong Province, China. In 2002 and 2003,
      a total of 2,710 participants aged 35-65 years received an endoscopic examination
      with 5 biopsies taken from standard sites with pathological diagnosis, and serum
      samples were collected to detect MG7-Ag by serum-based Immunopolymerase chain
      reaction (PCR) assay. The sensitivity and specificity of MG7-Ag Immuno-PCR assay
      in detecting of gastric cancer were assessed. Of 2,710 participants, 148 (5.46%)
      were determined to be MG7-Ag positive. The sensitivity of MG7-Ag Immuno-PCR assay
      for the detection of gastric cancer was 77.5% (31 of 40 gastric cancer cases),
      the specificity was 95.62% (2,553 of 2,670 nongastric cancer subjects) and the
      accuracy was 73.12%. A total of 24 gastric cancer cases were in Stage I or II, of
      which 17 (70.8%) were MG7-Ag positive. However, the proportion of MG7-Ag
      positivity in subjects with superficial gastritis, chronic atrophic gastritis,
      intestinal metaplasia, indefinite dysplasia or dysplasia was ranged from 3.00% to
      5.61% in comparison with 77.5% in those with gastric cancer. Our findings suggest
      that MG7-Ag was a sensitive and specific serum biomarker and may have a potential
      for gastric cancer screening in the high-risk population.

PMID- 19588496
TI  - Quantitative detection of Merkel cell virus in human tissues and possible mode of
      transmission.
AB  - Merkel Cell Virus (MCV) is a newly discovered polyomavirus, recently found in a
      rare skin cancer, Merkel cell carcinoma (MCC). However, MCV has also been
      detected in some normal tissue samples. We tested and compared the relative
      quantity of the MCV in a set of diverse human tissue samples with the MCC
      samples. The levels of MCV in MCCs were over 60 times higher than the highest
      values in all other tissues. Low quantities of MCV were detected in diverse
      tissue samples independently of malignant or benign histologic status. Higher
      levels of the virus were found in the upper aerodigestive tract, digestive
      system, and saliva compared to the lung and genitourinary system samples. These
      results confirm that MCV is widespread in the human body and suggest a possible
      fecal-oral transmission route similar to the Hepatitis A virus. Despite
      widespread presence of the virus, it appears that only neuroendocrine skin cells
      are susceptible to transformation by MCV.

PMID- 19588497
TI  - Age distribution of human papillomavirus infection and cervical neoplasia
      reflects caveats of cervical screening policies.
AB  - Although a second age-related peak of human papillomavirus (HPV) infection is
      observed in many populations, it does not seem to have any impact on cervical
      screening policies. We examined the age-specific prevalence of HPV infection
      among 2,604 women enrolled for cervical screening and correlated the age at
      diagnosis of 2,491 cervical intraepithelial neoplasia Grade 2/3 (CIN2/3) lesions
      and 801 invasive cervical cancers (ICC). Two peaks of HPV infection were detected
      at 26-30 and 46-50 years, respectively. The first infection peak was followed by
      a CIN2/3 peak and an ICC peak at 5-15 and 15 years later, respectively. The
      second infection peak was followed by an ICC peak 20 years later, but strikingly
      no CIN2/3 peak was detected in between and thus eliminated an opportunity of
      treating the lesions at preinvasive stages. The most plausible explanation is
      that women at the expected second CIN2/3 peak (50-65 years) are not having Pap
      smears under the current opportunistic screening program. Furthermore, women of
      this age may have physiological retraction of the transformation zone, and CIN
      lesions may remain undetected if an adequate Pap smear sample is not obtained. To
      combat this problem, the screening program in Hong Kong needs to focus on women
      aged 50 years and older and a mop-up screening up to 75 years is necessary.
      Bimodal peaks of HPV infection and cervical cancer are seen in many countries and
      the analysis of population-specific age distribution of CIN2/3 should be an
      integral exercise in evaluating the effectiveness of a screening program.

PMID- 19588498
TI  - Fluorescence lifetime imaging microscopy of chemotherapy-induced apoptosis
      resistance in a syngenic mouse tumor model.
AB  - During cancer therapy with DNA-damaging drug-agents, the development of secondary
      resistance to apoptosis can be observed. In the search for novel therapeutic
      approaches that can be used in these cases, we monitored chemotherapy-induced
      apoptosis resistance in a syngenic mouse tumor model. For this, syngenic murine
      colorectal carcinoma cells, which stably expressed a FRET-based caspase-3
      activity sensor, were introduced into animals to induce peritoneal carcinomatosis
      or disseminated hepatic metastases. This syngenic system allowed in vitro, in
      vivo and ex vivo analysis of chemotherapy induced apoptosis induction by
      optically monitoring the caspase-3 sensor state in the tumor cells. Tumor tissue
      analysis of 5-FU treated mice showed the selection of 5-FU-induced apoptosis
      resistant tumor cells. These and chemo-naive fluorescent tumor cells could be re
      isolated from treated and untreated mice and propagated in cell culture. Re
      exposure to 5-FU and second line treatment modalities in this ex-vivo setting
      showed that 5-FU induced apoptosis resistance could be alleviated by imatinib
      mesylate (Gleevec). We thus show that syngenic mouse systems that stably express
      a FRET-based caspase-3 sensor can be employed to analyse the therapeutic
      efficiency of apoptosis inducing chemotherapy.

PMID- 19588499
TI  - A case-control study of colorectal cancer detection by quantification of DNA
      isolated from directly collected exfoliated colonocytes.
AB  - This pilot study aimed to assess an original test based on the analysis of
      exfoliated colonocytes as a new approach to colorectal cancer (CRC) detection.
      DNA was isolated from exfoliated cells collected from the surface of the rectal
      mucosa by a standardized minimally invasive procedure in a case-control trial
      involving 66 patients with CRC diagnosis and 110 healthy volunteers (age 50-70).
      PicoGreen staining and quantitative real-time PCR (QRTPCR) were used for DNA
      quantification. Mean DNA scores in microg/ml obtained for the control and cancer
      groups were 2.1 (95% CI 1.7-2.5) and 9.0 (CI 6.7-11.2) respectively (p < 0.001)
      for PicoGreen and 0.8 (CI 0.6-0.9) and 3.8 (CI 1.9-5.7) respectively (p = 0.003)
      for QRTPCR. The PicoGreen assay better detected CRC presence. At DNA score cut
      off point of 2.5 microg/ml this assay gave sensitivities of 77.8% (CI 52.4-93.6)
      for proximal tumours, 91.4% (CI 76.9-98.2) for distal CRC and 86.8% (CI 74.7
      94.5) for all CRC with specificity at 74.0% (CI 64.0-82.4). Increasing the cut
      off point to 5.0 microg/ml resulted in sensitivities of 38.9% (CI 17.3-64.3) for
      proximal tumours, 71.4% (CI 53.7-85.4) for distal CRC and 60.4% (CI 46.0-73.5)
      for all CRC. Specificity for this cut-off point increased to 94.8% (CI 88.3
      98.3). The new procedure of exfoliated cell collection from the surface of the
      rectal mucosa is a simple, safe and well-tolerated technique providing high
      quality cells. These early results suggest that exfoliated cell collection in
      combination with DNA quantification can potentially be employed as a tool for CRC
      early detection.

PMID- 19588500
TI  - Biological effects induced by insulin-like growth factor binding protein 3 (IGFBP
      3) in malignant melanoma.
AB  - The insulin like growth factor (IGF) signaling pathway has been shown to
      contribute to melanoma progression, but little is known about the role of the IGF
      binding protein 3 (IGFBP-3) in melanoma biology. The aim of the present study was
      to characterize expression, function and regulation of IGFBP-3 in malignant
      melanomas and study its potential as a biomarker. The expression of IGFBP-3
      varied between different human melanoma cell lines and reintroduction of the
      protein in non-expressing cells led to induction of apoptosis. Interestingly, in
      cell lines expressing endogenous IGFBP-3, siRNA silencing of the protein led to a
      cell line-dependent decrease in proliferation, but had no effect on apoptosis and
      invasion. Examination of patient material showed that IGFBP-3 is unexpressed in
      benign nevi while a slight increase in protein expression was seen in primary and
      metastatic melanoma. However, expression of the protein was low and no
      correlation was found with circulating levels of IGFBP-3 in serum, suggesting
      that IGFBP-3 has limited potential as a predictive marker in malignant melanoma.
      We showed that promoter methylation of IGFBP-3 occurred in both melanoma cell
      lines and patient material, implicating epigenetic silencing as a regulation
      mechanism. Furthermore, expression of the protein was shown to be regulated by
      the PI3-kinase/AKT and MAPK/ERK1/2 pathways. In summary, our findings suggest
      that IGFBP-3 can exert dual functional effects influencing both apoptosis and
      proliferation. Development of resistance to the antiproliferative effects of
      IGFBP-3 may be an important step in progression of malignant melanomas.

PMID- 19588501
TI  - Impacts of fluorouracil-metabolizing enzymes on the outcomes of patients treated
      with S-1 alone or S-1 plus cisplatin for first-line treatment of advanced gastric
      cancer.
AB  - A phase III trial of S-1 plus cisplatin (SP) versus S-1 alone, for first-line
      treatment of advanced gastric cancer (SPIRITS trial), has shown that overall
      survival was better in patients treated with SP than with S-1 alone. In the
      present retrospective biomarker study, we aimed to develop a methodology to
      identify the patients with advanced gastric cancer who would respond better to S
      1 alone than SP. We studied 120 patients who received S-1 alone or SP for first
      line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA
      levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate
      phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular
      endothelial growth factor-A, and epidermal growth factor receptor in paraffin
      embedded specimens of primary tumors. Multivariate survival analysis in patients
      who received S-1 monotherapy (66 patients) demonstrated that low TP expression
      (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and
      high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall
      survival. In patients with lower expression of both TP and TS (n = 23) than their
      cutoff values, the S-1 alone group (n = 15) had longer overall survival than the
      SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas
      the frequency of overall adverse events in the S-1 alone group tended to be lower
      than that in SP group. Our results suggest that these biomarkers are useful for
      selection of patients with advanced gastric cancer in whom treatment with S-1
      alone will yield survival benefit.

PMID- 19588503
TI  - Cancer and viral infections in immunocompromised individuals.
AB  - Over the last 30 years, the increasing use of organ and stem cell transplantation
      and the AIDS epidemic have led to the realization that some, but not all, human
      cancers occur more frequently in immunosuppressed individuals. With the notable
      exception of non-melanoma skin cancer (NMSC), most tumors that show strongly
      increased incidence rates in both transplant recipients and AIDS patients have
      been found to have a viral etiology. Among these are Kaposi sarcoma, diffuse
      large cell B-cell lymphoma, cervical cancer, liver cancer, Merkel cell carcinoma
      and a subset of Hodgkin's disease. A viral etiology for NMSC, i.e., beta- and
      gamma-subtypes of human papillomavirus, has been suggested and investigated for
      many years, but remains controversial. In addition, the moderately increased
      incidence rates of several other cancers in immunosuppressed individuals (e.g.,
      Vajdic and van Leeuwen, Int J Cancer, in press) could indicate that additional
      infectious causes for at least some human cancers remain to be discovered. The
      controversy surrounding the role of cutaneous papillomavirus subtypes in the
      pathogenesis of NMSC illustrates the difficulties encountered when weighing the
      epidemiological and molecular biology evidence arguing for an involvement of
      highly prevalent viruses in certain types of cancer.

PMID- 19588502
TI  - Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory
      peptide fused to a thermally responsive polypeptide carrier.
AB  - Current treatment of solid tumors is limited by normal tissue tolerance,
      resulting in a narrow therapeutic index. To increase drug specificity and
      efficacy and to reduce toxicity in normal tissues, we have developed a
      polypeptide carrier for a cell cycle inhibitory peptide, which has the potential
      to be thermally targeted to the tumor site. The design of this polypeptide is
      based on elastin-like polypeptide (ELP). The coding sequence of ELP was modified
      by the addition of the cell penetrating peptide Bac-7 at the N-terminus and a 23
      amino acid peptide derived from p21 at the C-terminus (Bac-ELP1-p21). Bac-ELP1
      p21 is soluble in aqueous solutions below physiological temperature (37 degrees
      C) but aggregates when the temperature is raised above 39 degrees C, making it a
      promising thermally responsive therapeutic carrier that may be actively targeted
      to solid tumors by application of focused hyperthermia. While Bac-ELP1-p21 at 37
      degrees C did not have any effect on SKOV-3 cell proliferation, the use of
      hyperthermia increased the antiproliferative effect of Bac-ELP1-p21 compared with
      a thermally unresponsive control polypeptide. Bac-ELP1-p21 displayed both a
      cytoplasmic and nuclear distribution in the SKOV-3 cells, with nuclear-localized
      polypeptide enriched in the heated cells, as revealed by confocal microscopy.
      Using Western blotting, we show that Bac-ELP1-p21 caused a decrease in Rb
      phosphorylation levels in cells treated at 42 degrees C. The polypeptide also
      induced caspase activation, PARP cleavage, and cell cycle arrest in S-phase and
      G2/M-phase. These studies indicate that ELP is a promising macromolecular carrier
      for the delivery of cell cycle inhibitory peptides to solid tumors.

PMID- 19588504
TI  - A case-control study on hormone therapy as a risk factor for breast cancer in
      Finland: Intrauterine system carries a risk as well.
AB  - The purpose of this study was to evaluate the association between postmenopausal
      hormone therapy (HT) and the risk for breast cancer in recently postmenopausal
      Finnish women. All Finnish women with first invasive breast cancer diagnosed
      between the ages of 50 and 62 years during 1995-2007 (n = 9,956) were identified
      from the Finnish Cancer Registry. For each case, 3 controls of the same age were
      retrieved from the Finnish Population Register. The cases and controls were
      linked to the national medical reimbursement register to assess the use of HT.
      The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were
      calculated with conditional logistic regression analysis, adjusting for parity,
      age at the first birth and health care district. Estradiol-only therapy (991
      users with breast cancer, n) or oral progestagen (n = 138) was not accompanied by
      an increased risk. Estradiol-progestagen therapy (EPT) (n = 1,731) was associated
      with an elevated risk in the whole series (OR 1.36; 95% CI 1.27-1.46). The risk
      became detectable in less than 3 years of use. Continuous EPT use tended to be
      associated with a higher risk for breast cancer than the sequential EPT use. The
      use of tibolone (n = 80) (1.36; 1.15-1.96), a levonorgestrel-releasing
      intrauterine system (LNG-IUS) alone (n = 154) (1.45; 1.97-1.77) or as a
      complement to estradiol (n = 137) (2.15; 1.72-2.68) was also associated with an
      increased risk. The association between HT use and the risk for breast cancer
      shows a large variation between various forms of HT, and also the use of LNG-IUS
      may carry a risk.

PMID- 19588505
TI  - Risk of testicular cancer according to birthplace and birth cohort in Denmark.
AB  - Based on the intriguing finding of an east-west gradient of testicular cancer
      risk in the Nordic countries with a low risk in Finland, intermediate in Sweden,
      and high risk in Denmark, it was suggested that national practices rather than
      individual behavior may be important in the etiology of this cancer. We
      investigated the risk of testicular cancer in all men born in Denmark, 1931-1969
      according to birthplace. Testicular cancer information was derived from the
      Danish Cancer Registry and population data from Statistics Denmark. There was a
      several fold geographical variation in testicular cancer risk within Denmark.
      Among men born in the early period, 1931-39, the highest risk was primarily
      observed in the western part of Denmark whereas no such gradient was observed in
      more recent cohorts. The incidence of testicular cancer increased in all counties
      from the earliest to the latest birth cohort, but the increase was highest in the
      eastern parts of Denmark. The heterogeneity in risk according to place of birth
      within Denmark suggests that individual behavior plays an important role for the
      risk of testicular cancer. Based on the Danish data, the factor that may have
      caused the east-west gradient in testicular cancer risk appears to have been more
      unevenly distributed in the early part of the past century compared to more
      recent times.

PMID- 19588507
TI  - The Janus-faced role of ezrin in "linking" cells to either normal or metastatic
      phenotype.
AB  - In the majority of eukaryotic cells, the ezrin, radixin and moesin (ERM) proteins
      are involved in many physiologic functions including regulation of actin
      cytoskeleton, control of cell shape, adhesion, motility and modulation of signal
      transduction pathways. In a previous study, we used a dominant negative ezrin
      mutant to address ezrin involvement in remodeling of actin cytoskeleton and
      subsequently we depicted ezrin key role in melanoma cell migration and
      progression. Herein, we highlight recent advances on ezrin involvement in the
      metastatic phenomenon, including also some more neglected ezrin-related
      functions. Novel molecular processes driven by ezrin activation include:
      phagocytosis, acquisition of resistance to chemotherapeutics and triggering of
      programmed cell death signals. Recent data support an integrated role of ezrin
      also in development of tumor malignancy. On one hand, ezrin may be responsible of
      deranged execution of specific known functions such as adhesion and motility and
      on the other, it may also participate to unique metastatic determinants, through
      the establishment of aberrant linkages with tumor-related proteins. For instance,
      ezrin misslocalization, absence or deranged activity has started to be correlated
      with tumor progression in many tumors of different species, including humans.
      Concomitantly, ezrin may act simultaneously as a regulatory or deregulatory
      chaperon in both normal and tumor cells. It is still to be established whether
      this Janus-faced feature of ezrin is due to some unknown transforming Zelig-like
      property or to the fact that a tumor-associated molecule preferentially links to
      ezrin thus distracting it from its normal connections. However, the contribution
      of ezrin functional deregulation to the acquisition of the metastatic phenotype
      appears clear and ezrin or ezrin aberrant associations may represent good
      candidates for future anti-tumor therapies.

PMID- 19588506
TI  - Gene transfer of NK4, an angiogenesis inhibitor, induces CT26 tumor regression
      via tumor-specific T lymphocyte activation.
AB  - Hepatocyte growth factor (HGF) has been shown to be involved in malignant
      behaviors, such as invasion and metastasis, in different tumors. Hence, HGF could
      be a target molecule for control of the malignant potential of cancer. NK4 is a
      competitive antagonist for HGF and exerts an antitumor activity, not only by HGF
      antagonism but also by antiangiogenesis. Here, we studied the participation of
      cellular immunity in CT26 tumor regression by NK4 gene transfer. In vivo
      experiments showed that NK4-induced inhibition of subcutaneous tumor growth (as
      demonstrated in immunocompetent BALB/c mice) was weakened in T lymphocyte
      deficient nude mice. In addition, the immunocompetent BALB/c mice that had shown
      complete regression of CT26-NK4 tumors generated an immune memory against
      repeated challenge with the same tumor antigen. Immunohistochemistry of tumor
      infiltrating lymphocytes showed that the ratio of CD8/CD4 in CT26-NK4 tumors was
      significantly higher than that in control tumors. Also, the presence of tumor
      specific cytotoxic T lymphocytes (CTL) was demonstrated by cytotoxicity assays.
      Depletion of CD8+ T lymphocytes markedly abrogated the antitumor activity of NK4.
      However, NK4 had no direct effect on the in vitro cellular immune system. Taken
      together, these data indicate that NK4 expression by gene transfer, at the tumor
      site, triggers tumor-specific CTL activation, resulting in complete CT26 tumor
      regression in vivo. This action was considered to be due to apoptosis induced by
      NK4's potent antiangiogenic and HGF antagonistic effects.

PMID- 19588508
TI  - Down regulation of membrane-bound Neu3 constitutes a new potential marker for
      childhood acute lymphoblastic leukemia and induces apoptosis suppression of
      neoplastic cells.
AB  - Membrane-linked sialidase Neu3 is a key enzyme for the extralysosomal catabolism
      of gangliosides. In this respect, it regulates pivotal cell surface events,
      including trans-membrane signaling, and plays an essential role in
      carcinogenesis. In this report, we demonstrated that acute lymphoblastic leukemia
      (ALL), lymphoblasts (primary cells from patients and cell lines) are
      characterized by a marked down-regulation of Neu3 in terms of both gene
      expression (-30 to 40%) and enzymatic activity toward ganglioside GD1a (-25.6 to
      30.6%), when compared with cells from healthy controls. Induced overexpression of
      Neu3 in the ALL-cell line, MOLT-4, led to a significant increase of ceramide
      (+66%) and to a parallel decrease of lactosylceramide (-55%). These events
      strongly guided lymphoblasts to apoptosis, as we assessed by the decrease in
      Bcl2/Bax ratio, the accumulation of Neu3 transfected cells in the sub G0-G1 phase
      of the cell cycle, the enhanced annexin-V positivity, the higher cleavage of
      procaspase-3. Therefore, the reduced expression of Neu3 in ALL could help
      lymphoblasts to survive, maintaining the cellular content of ceramide below a
      critical level. Interestingly, we found that Neu3 activity varied in relation to
      disease progression, increasing in clinical remission after chemotherapy, and
      decreasing again in patients that relapsed. In addition, a negative correlation
      was observed between Neu3 expression and the percentage of the ALL marker 9
      OAcGD3 positive cells. Consequently, Neu3 could represent a new potent biomarker
      in childhood ALL, to assess the efficacy of therapeutic protocols and to rapidly
      identify an eventual relapse.

PMID- 19588510
TI  - Adverse childhood events are associated with obesity and disordered eating:
      results from a U.S. population-based survey of young adults.
AB  - The authors investigated the relationship between childhood abuse and obesity in
      young adulthood (M age = 22) in a large, U.S. representative sample (N = 15,197).
      Controlling for demographics and depression, men with a history of childhood
      sexual abuse were at increased risk of overweight and obesity. No association
      between childhood abuse and obesity or overweight was observed for women in this
      sample. Higher percentages of skipping meals to lose weight and problematic
      eating were observed among women with a history of physical abuse. This is the
      first study to note an association between childhood abuse with obesity and
      problematic weight management behaviors in a sample of young adults.

PMID- 19588511
TI  - The effects of PTSD symptomatology on laboratory-based aggression.
AB  - The present study sought to examine the relationship between posttraumatic stress
      disorder (PTSD) symptomatology and aggression using a highly controlled, quasi
      experimental laboratory-based aggression paradigm among a sample of 85
      undergraduate students not help-seeking for current PTSD phenomena. Congruent
      with theory and past research, results showed that PTSD symptomatology was
      positively associated with aggression. In demonstrating this effect using a
      laboratory-based methodology, the present study provides a heuristic for future
      researchers to explore potential mediators and moderators of the PTSD-aggression
      relationship.

PMID- 19588509
TI  - Selective upregulation of interleukin-8 by human rhabdomyosarcomas in response to
      hypoxia: therapeutic implications.
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of adolescence and
      childhood. Because RMS tumors are highly vascularized, we sought to determine
      which factors secreted by RMS cells are crucial in stimulating angiogenesis in
      response to hypoxia. To address this issue, we evaluated expression of several
      proangiogenic factors [interleukin (IL)-8, vascular endothelial growth factor
      (VEGF), fibroblast growth factor (FGF)-2, stromal-derived factor (SDF)-1,
      hepatocyte growth factor (HGF) and leukemia inhibitory factor (LIF)] in 8 human
      RMS cell lines in both normal steady-state and hypoxic conditions. We found by
      real-time quantitative polymerase chain reaction (RQ-PCR) and confirmed by enzyme
      linked immunosorbent assay (ELISA) that from all the factors evaluated, IL-8,
      whose expression is very low in normoxia, had been very highly expressed and
      secreted by RMS cells lines during hypoxic conditions ( approximately 40-170
      times). Interestingly, this upregulation was not affected by knocking down
      hypoxia-inducible factor (HIF)-1alpha, but was inhibited by mitogen-activated
      protein kinase (MAPK)p42/44 and phosphatidylinositaol 3-kinase (PI3K)/AKT pathway
      inhibitors. This suggests that IL-8 expression is regulated in an activating
      protein (AP)-1- and nuclear factor (NF)-kappaB-dependent manner. Furthermore, we
      found that conditioned media (CM) harvested from RMS cells exposed to hypoxia
      activated and stimulated chemotactic responses in human umbilical vein
      endothelial cells (HUVECs) and that IL-8 was responsible for hypoxia-related
      effects. Finally, by employing shRNA, the expression of IL-8 in human RH-30 cells
      was downregulated. We noticed that such RMS cells, if injected into skeletal
      muscles of immunodeficient mice, have a reduced ability for tumor formation. We
      conclude that IL-8 is a pivotal proangiogenic factor released by human RMS cells
      in hypoxic conditions and that the targeting of IL-8 may prove to be a novel and
      efficient strategy for inhibiting RMS growth.

PMID- 19588512
TI  - Work limitations in employed persons seeking treatment for chronic posttraumatic
      stress disorder.
AB  - This preliminary study examined work limitations in 27 employed persons seeking
      treatment for chronic posttraumatic stress disorder (PTSD) using the Work
      Limitations Questionnaire (Lerner et al., 2001). Results showed that this sample
      experienced an impaired ability to perform time management demands, output
      demands, and mental-interpersonal demands at work. This study adds new knowledge
      on the scope of work impairment of PTSD and identifies the important need for
      developing work-focused measurement tools and interventions.

PMID- 19588513
TI  - Participant reactions to a pretreatment research assessment during a treatment
      outcome study for PTSD.
AB  - Participants' reactions to pretreatment assessments have not been studied as part
      of a randomized clinical trial (RCT) for posttraumatic stress disorder (PTSD).
      The current study examined participants' reactions in women with PTSD who
      completed pretreatment assessments during an RCT. We assessed participant
      reactions (N = 100) to a pretreatment assessment that included self-report
      questionnaires, interviews, and psychophysiological assessment. Results indicated
      that participation in pretreatment assessment was well tolerated as measured by
      participants' reports of distress, interest level, perceptions of the
      appropriateness of assessment length, and willingness to participate in a similar
      assessment in the future. Participating in lengthy pretreatment assessments did
      not adversely impact treatment participation or outcome.

PMID- 19588514
TI  - The relationship of posttraumatic growth to peritraumatic reactions and
      posttraumatic stress symptoms among Sri Lankan university students.
AB  - The relationships of posttraumatic growth to peritraumatic reactions and
      posttraumatic stress symptoms were examined in 93 Sri Lankan university students
      who had experienced a traumatic life event. Posttraumatic growth was associated
      with peritraumatic dissociation and posttraumatic stress symptoms, but was not
      associated with peritraumatic emotional distress. Results indicated a curvilinear
      relationship between peritraumatic dissociation and posttraumatic growth and
      between posttraumatic stress symptoms and posttraumatic growth. In a regression
      model predicting posttraumatic growth scores, each of the quadratic relationships
      of peritraumatic dissociation and posttraumatic stress symptoms to posttraumatic
      growth were statistically significant, and combined accounted for 22% of the
      variance. Results suggest that moderate levels of peritraumatic dissociation and
      symptoms are most associated with the greatest levels of growth.

PMID- 19588515
TI  - Male-to-female sexual aggression among Iraq, Afghanistan, and Vietnam veterans:
      co-occurring substance abuse and intimate partner aggression.
AB  - The current study examined the frequency and correlates of coercive sexual
      behaviors by male Iraq, Afghanistan, and/or Vietnam veterans recruited from a
      Veterans Affairs trauma recovery clinic (n = 92) toward their female partners.
      Men who reported sexual aggression in the past year (n = 37) compared to men who
      did not report sexual aggression in the past year (n = 55) more frequently
      reported impulsive aggression, dominating/isolating, and physically assaulting
      their partner, and were more likely to have a substance abuse diagnosis. Sexually
      aggressive men were significantly less likely than nonsexually aggressive men to
      have a diagnosis of depression. Posttraumatic stress disorder, an established
      risk factor for nonsexual partner aggression among veterans, was not associated
      with sexual aggression.

PMID- 19588516
TI  - Current status of diagnosis and prognosis of infant acute leukemia in China.
AB  - OBJECTIVE: Treatment and outcome of infant acute leukemia (IAL) in developed
      countries have been well documented. However, reports summarizing diagnosis and
      outcome of IAL in developing countries are limited. METHODS: Five hundred ninety
      seven pediatric patients were diagnosed with acute leukemia in our hospital
      between January 1997 and June 2008, of which 19 were younger than 12 months. Data
      from our 19 cases and the Chinese literature were analyzed. RESULTS: Of the 19
      cases, 14 had acute lymphoblastic leukemia (ALL) and 5 had acute myeloid leukemia
      (AML) based on FAB classification. Immunophenotyping and molecular genetic
      analysis were performed in only 6 cases. Only 16% (3/19) of the infants received
      treatment. Two infants with immunophenotypic AML who abandoned treatment achieved
      spontaneous remission without chemotherapy within 2 and 4 months respectively.
      Combining our data with those from Chinese literature, less than one third of the
      infants had immunophenotypic and genetic verification of leukemia and 29% (18/63)
      of them received treatment. CONCLUSION: Family financial difficulties and
      physicians' lack of confidence in treatment outcome in IAL contributed to a high
      treatment abandonment rate and poor outcome. Public health insurance as well as
      physician education on current IAL treatment strategies may decrease treatment
      abandonment in China.

PMID- 19588518
TI  - Morphological and crystallographic evolution of bainite transformation in Fe
      0.15C binary alloy.
AB  - In this article, an in situ observation method, combining laser scanning confocal
      microscopy and electron backscattering diffraction, was used to investigate the
      morphological and crystallographic evolution of bainite transformation in a Fe
      0.15C binary alloy. The nucleation at a grain boundary and inclusions,
      sympathetic nucleation, and impingement event of bainitic ferrite were directly
      shown in real time. The variant evolution during bainite transformation and
      misorientation between bainitic ferrites were clarified. Strong variant selection
      was observed during sympathetic nucleation.

PMID- 19588519
TI  - Predictive power of pretreatment prognostic factors in children with
      hepatoblastoma: a report from the Children's Oncology Group.
AB  - BACKGROUND: PRETEXT is used to stratify risk in children with hepatoblastoma by
      the Liver Tumor Strategy Group (SIOPEL) of the International Society of Pediatric
      Oncology (SIOP). A recent analysis excluding patients that did not survive
      neoadjuvant chemotherapy, concluded that PRETEXT was superior to Children's
      Oncology Group (COG) stage for predicting survival. Puzzled by this result, we
      made a similar comparison of PRETEXT and COG stage. This time, however, we
      include all patients, and we compare predictive value at diagnosis, instead of
      after neoadjuvant chemotherapy. METHODS: Hepatoblastoma patients in INT-0098 were
      retrospectively reviewed for PRETEXT and other potential prognostic factors
      including pathologic subtype, and alpha-fetoprotein (AFP). RESULTS: Five-year
      overall survival by PRETEXT was 88.9%, 84.5%, 71.6%, and 30.9%, for PRETEXT I,
      II, III, and IV, respectively. The 5-year overall survival rates by COG stage
      were 100%, 97.5%, 100%, 70.2%, and 39.3% for Stage I pure fetal histology (PFH),
      Stage I unfavorable histology (UH = not PFH), Stage II, Stage III, and Stage IV,
      respectively. PRETEXT added significant additional prognostic information within
      the COG Stage III, but not COG Stage IV. Additional prognostic factors
      statistically significant for an increased risk of death were small-cell
      undifferentiated (SCU) histologic subtype and AFP < 100 at diagnosis.
      CONCLUSIONS: PRETEXT, COG stage, SCU histology, and AFP < 100, as assessed at
      diagnosis, are important determinants of survival that will allow us to better
      develop common international criteria for risk stratification. Common risk
      stratification is an essential prerequisite to establish effective cooperation
      across the ocean in this field of rare tumors.

PMID- 19588520
TI  - The carotid artery: an organ at risk and often neglected.

PMID- 19588521
TI  - Vincristine: Can its therapeutic index be enhanced?
AB  - Vincristine is one of the most widely used and more effective drugs in paediatric
      oncology. The dose-limiting toxicity of neuropathy, lack of proven
      neuroprotective measures and an incomplete understanding of the pharmacokinetics
      and pharmacogenetics of vincristine have limited its therapeutic potential.
      Recent advances in the understanding of vincristine pharmacokinetics and
      pharmacogenetics, and potential methods of preventing neurotoxicity are reviewed
      which could enable dose escalation and dose individualisation in order to enhance
      the therapeutic index.

PMID- 19588522
TI  - Long-term impact of cancer care on activities of daily living: are we causing our
      sarcoma survivors to grow up too quickly?

PMID- 19588524
TI  - Rapid regression of lymphadenopathy upon rapamycin treatment in a child with
      autoimmune lymphoproliferative syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of the
      immune system caused by inadequate induction of apoptosis via the Fas pathway,
      mainly characterized by generalized lymphadenopathy, splenomegaly, and autoimmune
      cytopenias, as well as increased risk of lymphoma. Although the clinical course
      of ALPS is highly variable, without treatment long-term prognosis is
      unsatisfactory for most patients. ALPS has been treated with most of the existing
      immunosuppressive agents, with variable success. We hereby present a case of a
      child with ALPS whose greatly enlarged lymph nodes rapidly regressed upon
      initiation of rapamycin, a novel potential therapeutic agent in the treatment of
      ALPS.

PMID- 19588523
TI  - Candidate mechanisms accounting for effects of physical activity on breast
      carcinogenesis.
AB  - Evidence is strong that a reduction in risk for breast cancer is associated with
      moderate to vigorous physical activity (PA); however, there is limited
      understanding of the role of type, intensity, duration, and frequency of PA and
      their mechanisms in accounting for this health benefit. The objective of this
      review is to stimulate investigations of candidate mechanisms that may account
      for the effects of the intensity and duration of aerobic PA on breast cancer risk
      and tumor burden. Three hypotheses are considered: 1) the mTOR network
      hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR
      signaling network in mammary carcinomas; 2) the hormesis hypothesis: the
      carcinogenic response to PA is nonlinear and accounted for by a physiological
      cellular stress response; and 3) the metabolic reprogramming hypothesis: PA
      limits the amount of glucose and glutamine available to mammary carcinomas
      thereby inducing apoptosis because tumor-associated metabolic programming is
      reversed. To link these hypotheses to systemic effects of PA, it is recommended
      that consideration be given to determining: 1) what contracting muscle releases
      into circulation or removes from circulation that would directly modulate the
      carcinogenic process in epithelial cells; 2) whether the effects of muscle
      contraction on epithelial cell carcinogenesis are exerted in an endocrine,
      paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle
      contraction on malignant cells differ from effects on normal or premalignant
      cells that do not manifest the hallmarks of malignancy.

PMID- 19588525
TI  - Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine
      sediments: a randomized, open-label, parallel-group pilot study.
AB  - BACKGROUND: Dutasteride is commonly used in patients that are also at risk for
      prostate cancer (PCa). Therefore, the influence of dutasteride on PCa markers has
      to be studied. To date, only the effect of dutasteride on serum prostate-specific
      antigen (PSA) has been studied. This was the first study to investigate the
      effect of dutasteride on the new PCa marker PCA3, longitudinally and in a dose
      dependent manner. METHODS: From April 25, 2005 to October 31, 2006, 16 subjects
      with benign prostatic hyperplasia (BPH) and 9 subjects with clinically localized
      PCa were enrolled at the urological outpatient clinics of one university hospital
      and one community hospital. Eight subjects with BPH and five with PCa received
      0.5 mg dutasteride once daily for 3 months, eight with BPH and four with PCa
      received 3.5 mg. No subjects were withdrawn because of adverse effects. RESULTS:
      In all four groups both 0.5 and 3.5 mg dutasteride had a variable effect on the
      PCA3 score. In contrast, its other effects were consistent as it rapidly reduced
      serum DHT by >or=90%, over time increased serum T by 20-30%, over time halved
      serum PSA and decreased prostate volume by 10-16%. CONCLUSIONS: In this
      exploratory/pilot study the effect of dutasteride on the PCA3 score was variable.
      This should be taken into account while using PCA3 in diagnostics. As this study
      was exploratory, the influence of androgen-deprivation therapy on the PCA3 score
      should be analyzed further.

PMID- 19588526
TI  - Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth.
AB  - BACKGROUND: Recent reports have linked the survival-promoting effect of CXCR4 to
      the up regulation of Bcl-2 protein expression. MATERIALS AND METHODS: To further
      elucidate the relationship between Bcl-2 and CXCR4, tumorigenicity was evaluated
      in in vitro and in vivo models following treatment with CTCE-9908, a CXCR4
      antagonist peptide. RESULTS: In vitro, CTCE-9908 inhibited cellular proliferation
      in PC-3-Bcl-2 and PC-3-Neo cell lines Furthermore in our xenograft model, CTCE
      9908 delivered via daily intraperitoneal injections resulted in a statistically
      significant reduction in tumor size compared to control (396 + 205 mm(3) vs.
      1,010 + 215 mm(3) respectively, p < 0.05) in the Bcl-2 expressing tumors. This
      reduction was associated with knockdown of VEGF, inhibition of angiogenesis and
      lymphangiogenesis, and induction of apoptosis. CTCE-9908 therapy was also
      associated with a marked reduction in intra-tumoral host cells expressing VEGFR1
      and CD11b myeloid-derived suppressor cells (MDSC). CONCLUSION: These data show
      that CXCR4 antagonists represent a valuable addition to the cancer therapeutic
      arsenal. Such agents may have beneficial synergistic dual-effects in reducing
      tumor cell proliferation directly, and indirectly through perturbation of the
      tumor microenvironment. Further studies of the novel CTCE-9908 compound in
      prostate and other solid tumor inhibition are warranted. Prostate 69: 1460-1469,
      2009. (c) 2009 Wiley-Liss, Inc.

PMID- 19588527
TI  - Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open
      fractures.
AB  - The increasing incidence of bacterial infection and the appearance of
      Staphylococcus aureus (S. aureus) strains that are resistant to commonly used
      antibiotics has made it important to develop non-antibiotic approaches for
      infection prevention. The aim of this study was to develop local monocyte
      chemoattractant protein-1 (MCP-1) and interleukin-12 p70 (IL-12 p70) therapies to
      prevent S. aureus infection by enhancing the recruitment and activation of
      macrophages, which are believed to play an important role in infection prevention
      as the first line of defense against invading pathogens. Nanocoating systems for
      MCP-1 and IL-12 p70 deliveries were prepared, and their release characteristics
      desirable for infection prevention in open fractures were explored. Local MCP-1
      therapy reduced S. aureus infection and influenced white blood cell populations,
      and local IL-12 p70 treatment had a more profound effect on preventing S. aureus
      infection. No synergistic relationship in decreasing S. aureus infection was
      observed when MCP-1 and IL-12 p70 treatments were combined. This reported new
      approach may reduce antibiotic use and antibiotic resistance.

PMID- 19588528
TI  - Wide-field spatial mapping of in vivo tattoo skin optical properties using
      modulated imaging.
AB  - BACKGROUND AND OBJECTIVES: Modulated imaging is a new modality capable of wide
      field, spatially resolved measurement of in vivo optical properties. Based on
      spatial light modulation, the method is inexpensive, non-contact, and allows
      spatial mapping of tissue absorption and reduced scattering coefficients at any
      wavelength between 450 and 1,100 nm. Currently, clinicians rely on qualitative
      visual inspection to guide parameter selection for laser-based tattoo removal. MI
      provides quantitative measurements of multi-colored tattooed skin which may help
      guide treatment and objectively assess response. STUDY DESIGN/MATERIALS AND
      METHODS: We have measured the spatially varying optical properties of multi
      colored tattooed skin over a 50 mm x 50 mm field of view at wavelengths ranging
      from 650 to 970 nm using MI. These measurements were compared to a similar field
      of view of non-tattooed skin from an adjacent area. RESULTS: We have determined
      the differentiated optical properties in vivo of multi-colored tattooed skin
      versus non-tattooed skin. CONCLUSIONS: MI provides spatially resolved
      quantitative information with potential for quantitative assessment of response
      to treatment and may provide guidance for laser tattoo removal in the future.

PMID- 19588529
TI  - Clinical evaluation of a single-wavelength fractional laser and a novel multi
      wavelength fractional laser in the treatment of photodamaged skin.
AB  - BACKGROUND AND OBJECTIVES: Nonablative fractional lasers are well recognized for
      rejuvenating photoaged skin. We previously reported favorable outcomes with short
      follow-up after the use of 1,440-nm Nd:YAG laser energy used alone or in
      combination with a 1,320-nm laser to effect rejuvenation and wrinkle reduction.
      We now report longer follow-up data. STUDY DESIGN/MATERIALS AND METHODS: Nineteen
      Caucasian subjects (average age 47+/-8.4; range 33-62) exhibiting mild-to
      moderate photoaging of the face and neck were treated four times (average
      interval 18.1+/- 4.1 days; range 11-37 days) with the 1,440-nm Nd:YAG fractional
      laser (average fluence 3.7+/-0.3 J/cm(2)) or the 1,320/1,440-nm multiplex Nd:YAG
      fractional laser (1,320-nm average fluence 8.4+/-0.4 J/cm(2); 1,440-nm average
      fluence 2.3+/-0.2 J/cm(2)). Outcomes were assessed by subjects and the treating
      physician using a quartile scale to evaluate skin tightening, surface texture,
      rhytids, dyschromia, erythema, and global appearance after 1, 3, and 6 months.
      Retroauricular punch biopsies from three patients were used to evaluate wound
      healing. Three patients withdrew from the study prior to evaluation, one missed
      the 1-month evaluation, and one missed the 6-month evaluation. RESULTS:
      Assessment by subjects and the treating physician revealed clinical improvement
      for all outcomes after 1, 3, and 6 months. The differences between the treatment
      groups were not statistically significant. Subjects demonstrated the greatest
      average 6-month improvements in surface texture and global skin appearance.
      Subjects treated with the multiplex laser reported more skin tightening than the
      group treated only with the 1,440-nm laser. Histological evaluation revealed
      wound healing within 10 days and significant neocollagenesis at 3 months. No
      adverse events were reported in any subject. CONCLUSION: The 1,440-nm Nd:YAG and
      1,320/1,440-nm multiplex Nd:YAG lasers safely and effectively produced improved
      surface texture, rhytids, dyschromia, erythema, global skin appearance, and skin
      tightening. Histopathologic findings correlated with clinical observations.

PMID- 19588530
TI  - Enhancement of bonding to enamel and dentin prepared by Er,Cr:YSGG laser.
AB  - BACKGROUND AND OBJECTIVE: Erbium lasers are potential tools to remove caries and
      dental hard tissue but bond strengths of composites to those preparations are
      reported to be lower than conventional methods. The purpose of this study was to
      evaluate the effect of mechanical excavation and/or chemical alteration on bond
      strength of composites to laser irradiated enamel and dentin. MATERIALS AND
      METHODS: Seventy-two premolars were ground to obtain flat enamel (E, n = 36) or
      dentin (D, n = 36) surfaces in both buccal and lingual cusps, divided into:
      LaserExcavation (LEx), LaserNo-excavation (LNex), and Bur (B) groups. The laser
      groups were irradiated for 10 seconds by Er,Cr:YSGG laser [4.5 W, 60% air, 80%
      water (enamel) 3 W, 60% air, 70% water (dentin)]. Irradiated surfaces in the
      excavation groups (Ex) were then mechanically smoothed with a dental excavator,
      prepared surfaces were then etched (37% H(3)PO(4)) for 20 or 40 seconds (enamel)
      and 15 or 30 seconds (dentin), washed (20 seconds), adhesive was applied(Single
      Bond Plus), and light cured (20 seconds). A composite cylinder (Filtek Supreme
      Plus) formed, placed and light cured (40 seconds). The specimens were stored (37
      degrees C,48 hours), shear bond tested (1 mm/minute), and statistically analyzed
      (P < 0.05). RESULTS: Mixed-model ANOVA showed significant differences between
      enamel (P = 0.0091) and between dentin groups (P = 0.0035). Tukey/Kramer showed
      mean shear bond strength (SBS+/-SE) of EB40 (27.01+/-2.38 MPa) was significantly
      higher than ELNoExc20 (14.39+/-2.5 MPa) and ELExc40 (14.90+/-2.28 MPa). Also DB30
      (17.57+/- 1.67 MPa) and DLExc30 (18.6+/-1.74 MPa) were significantly higher than
      DLNoExc15 (9.56+/-1.86 MPa). CONCLUSION: Increasing the etching time up to 40
      seconds or excavation of the laser prepared surface (but not the combination) may
      increase the bond strength to the level of conventional methods in enamel but
      excavation has a greater influence in dentin. Also the combination of both
      methods [excavation+longer etching time (30 seconds)] exhibit significantly
      better results in dentin.Mode of failure study showed mechanical excavation in
      both enamel and dentin can significantly reduce the cohesive failure in tooth
      structure.

PMID- 19588531
TI  - In vitro effect of carboplatin, cytarabine, paclitaxel, vincristine, and low
      power laser irradiation on murine mesenchymal stem cells.
AB  - BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are promising for use in
      regenerative medicine. Cytostatics can decrease, but low-power laser irradiation
      (LPLI) can increase the growth of MSCs. The interaction of LPLI, MSCs and
      cytostatics is not known. This study investigated the effect of four cytostatics
      (carboplatin, cytarabine, paclitaxel, vincristine), LPLI, and combination of a
      cytostatic drug and LPLI on murine MSCs (mMSCs). STUDY DESIGN/MATERIALS AND
      METHODS: MMSCs were exposed to LPLI (660 nm diode laser; 60 mW output power;
      range of power density: 76-156 mW/cm(2); range of energy density: 1.9-11.7
      J/cm(2)) and/or a cytostatic drug (carboplatin: 2, 10, 50; cytarabine: 0.4, 10,
      50; paclitaxel: 0.4, 2, 10; vincristine: 0.02, 0.1, 0.5 microg/ml, respectively).
      Cell proliferation was measured after 24, 48, or 72 hours incubation. RESULTS:
      LPLI at 1.9 J/cm(2) dose increased the proliferation rate with 41% after 48
      hours. However, 11.7 J/cm(2) LPLI caused 42% inhibition and cytostasis was still
      detectable after 72 hours. LPLI caused equivalent stimulation in single or in
      divided doses (3.8 vs. double 1.9 J/cm(2) in a 24-hour period). The cytotoxicity
      of 50 microg/ml carboplatin was eliminated, the inhibitory power of 0.1 microg/ml
      vincristine was attenuated by 1.9 J/cm(2) LPLI even 3 days post-treatment
      (attenuation >10%). The 11.7 J/cm(2) LPLI enhanced the cytotoxicity of 50
      microg/ml cytarabine (from 48% to 73%) and 10 microg/ml paclitaxel (from 37% to
      78%). Combination of the ineffective 0.4 microg/ml cytarabine or paclitaxel with
      the inhibitory 11.7 J/cm(2) LPLI exhibited stronger inhibition than the 11.7
      J/cm(2) LPLI alone (69% and 69% vs. 42%). CONCLUSIONS: Low energy density of LPLI
      increases and high energy density of LPLI decreases the proliferation of mMSCs.
      Furthermore, LPLI can prevent or attenuate some drug's cytotoxicity and amplify
      others'. The result depends on the applied energy density, on the type and
      concentration of the cytostatics.

PMID- 19588532
TI  - Treatment of hypertrophic and resistant port wine stains with a 755 nm laser: a
      case series of 20 patients.
AB  - BACKGROUND AND OBJECTIVE: Port wine stains (PWS) are heterogeneous vascular
      malformations that can be treated with vascular-selective pulsed dye lasers
      (PDL). Hypertrophic PWS, especially in adults, are consistently less responsive
      to PDL. Furthermore, many PWS that respond well initially to PDL treatment may
      reach a response plateau, becoming unresponsive to further PDL treatments, a
      phenomenon termed "treatment resistance." Based on the theory of selective
      photothermolysis, vessels in such lesions may also be specifically targeted with
      a 755 nm laser that has selectivity for deoxyhemoglobin as well as oxyhemoglobin
      and increased depth of skin penetration. STUDY DESIGN/PATIENTS AND METHODS:
      Retrospective case review of 20 patients with either hypertrophic or PDL
      resistant PWS treated with a 755 nm laser alone or in combination with other
      lasers, including PDL. RESULTS: Hypertrophic PWS showed significant lightening
      after treatment with a 755 nm laser in combination with PDL. Most PDL-resistant
      PWS showed moderate improvement after treatment with either a 755 nm laser alone
      or in combination with another laser, including PDL. Some lesions showed only
      mild improvement or did not respond. Serious side effects were infrequent. Most
      commonly encountered complications included pain, edema, bullae, crusting, and
      rare scarring. CONCLUSIONS: Alexandrite 755 nm laser can be useful for the
      treatment of hypertrophic and treatment-resistant PWS in adult and pediatric
      patients. Complications are infrequent and predictable. Careful attention to
      using a fluence at or near the threshold for clinical response with this deeply
      penetrating laser is essential to prevent serious sequelae.

PMID- 19588534
TI  - The effect of 595 nm pulsed dye laser on superficial and nodular basal cell
      carcinomas.
AB  - BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) have supporting
      vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The
      objective of this study was to determine the effect of repeated PDL treatments on
      BCCs of superficial and nodular subtypes and of varying diameters. STUDY
      DESIGN/MATERIALS AND METHODS: Twenty biopsy-proven BCCs received four 595 nm PDL
      treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were
      treated using a set of previously optimized laser parameters: one pass, 15 J/cm2
      energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The
      treated area was excised and evaluated histologically for residual tumor.
      Histologic response rates of the PDL treated BCCs were compared with that of non
      PDL treated, matched control tumors. RESULTS: Nearly all BCCs <1.5 cm in diameter
      (n = 12) showed complete response to four PDL treatments (91.7%; n = 11/12)
      versus 16.7% of controls (n = 2/12, P-value = 0.0003). BCCs > or =1.5 cm in
      diameter (n = 8) showed a complete response rate of 25% (n = 2/8) versus 0% of
      controls (n = 0/8, P-value = 0.2). Mean clinical tumor diameter of the complete
      responders was 1.1 cm (n = 13) versus 2.2 cm (n = 7) for incomplete responders (P
      value = 0.005). Tumor histologic types among the complete responders included
      superficial, nodular, micronodular, and keratinizing. Incompletely responding
      BCCs showed a significant reduction in tumor burden after PDL treatment, with
      residual histologic tumor burden ranging from <1% to 29% of the original clinical
      tumor diameter, compared to 13-68% residual tumor burden for the corresponding
      controls (P-value = 0.05). CONCLUSIONS: PDL is an effective means of reducing
      tumor burden in patients with large BCCs and may be an alternative therapy in
      BCCs <1.5 cm in diameter.

PMID- 19588533
TI  - Effects of non-invasive, 1,210 nm laser exposure on adipose tissue: results of a
      human pilot study.
AB  - BACKGROUND AND OBJECTIVES: Laser radiation (1,210 nm) has been previously shown
      to be capable of selective photothermolysis of adipose tissue in vitro when
      applied non-invasively. The objective of this pilot study was to evaluate the in
      vivo effects of this laser in human subjects. STUDY DESIGN/MATERIALS AND METHODS:
      Twenty-four adult subjects were exposed non-invasively on the abdomen to a 1,210
      nm laser at fluences of 70, 80, and 90 J/cm(2), with a 10 mm spot size, 5 seconds
      pre-cooling, and 3 seconds exposure duration delivered with parallel contact
      cooling. There was an impairment of the skin-cooling device during the study.
      Exposure and control sites were biopsied at either 1-3 days or 4-7 weeks. Tissue
      was processed for nitroblue tetrazolium chloride (NBTC) staining, a marker for
      thermal damage, and hematoxylin and eosin (H&E) staining. RESULTS: Laser
      exposures were painful, requiring local anesthesia in most subjects, but
      otherwise well tolerated. At 1-3 days after exposure, there was a fluence
      dependent loss of NBTC staining in the fat and dermis. In 2 of 14 subjects (2 of
      42 exposure sites) evaluated at 1-3 days after exposure, epidermal damage was
      noted within a small portion of the test site, likely due to impaired contact
      cooling. At 4-7 weeks, lipomembranous changes of the fat were seen in 89% of test
      sites and 33% of control sites. CONCLUSIONS: This in vivo study shows histologic
      evidence of laser-induced damage of fat. With further development, this might
      become a useful treatment for disorders involving the fat and/or lower dermis.

PMID- 19588535
TI  - Port wine stain progression: a potential consequence of delayed and inadequate
      treatment?
AB  - BACKGROUND AND OBJECTIVES: Port wine stains are congenital low-flow vascular
      malformations of the skin. Unlike hemangiomas, PWS do not involute with time, but
      rather if left untreated can hypertrophy and develop nodularity. Laser therapy of
      PWS particularly with pulsed-dye lasers, is a safe, well-established treatment
      that is successful in the majority of patients, especially for younger patients.
      Patients that fail to receive treatment early in life may subsequent develop
      lesions more likely to progress. STUDY DESIGN/PATIENTS AND METHODS: A case report
      and review of the literature are presented. We report a 43 year-old man born with
      a port-wine stain on the right side of his face that extended in the V2
      distribution on his face. He had undergone several sessions with a pulsed-dye
      laser, the sequential dual-wavelength (595 nm and 1064 nm) laser and a CO2
      resurfacing laser from the age of 26 but failed to follow through with a
      sufficient number of treatments to prevent hypertrophy. RESULTS: Due to an
      insufficient number and interval of treatments (with only 7 treatments over 16
      years starting at age 26) with the various lasers, the patient's port wine stain
      continued to progress in color and development of nodularity. CONCLUSIONS:
      Patients born with port wine stains should have early laser treatment to achieve
      optimal results. Delay in treatment, as in this patient until age 26, may result
      in hard to treat PWS that can continue to progress in nodularity. This case
      illustrates the hypertrophy and nodularity that can occur due to progression of a
      PWS with failure to follow through with sufficient number of laser treatments.

PMID- 19588536
TI  - Phototherapy promotes healing of chronic diabetic leg ulcers that failed to
      respond to other therapies.
AB  - OBJECTIVE: We tested the hypothesis that combined 660 and 890 nm LED phototherapy
      will promote healing of diabetic ulcers that failed to respond to other forms of
      treatment. RESEARCH DESIGN AND METHODS: A double-blind randomized placebo
      controlled design was used to study 23 diabetic leg ulcers in two groups of 14
      patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine
      cream and treated with "placebo" phototherapy (<1.0 J cm(-2)) twice per week,
      using a Dynatron Solaris 705(R) device. Group two ulcers were treated similarly
      but received 3 J cm(-2) dose. RESULTS: At each of 15, 30, 45, 60, 75, and 90 days
      of healing, mean ulcer granulation and healing rates were significantly higher
      for group two than the "placebo" group (P < 0.02). While "placebo" treated ulcers
      worsened during the initial 30 days, group two ulcers healed rapidly; achieving
      56% more granulation and 79.2% faster healing by day 30, and maintaining
      similarly higher rates of granulation and healing over the "placebo" group all
      through. By day 90, 58.3% of group two ulcers had healed fully and 75% had
      achieved 90-100% healing. In contrast, only one "placebo" treated ulcer healed
      fully by day 90; no other ulcer attained > or =90% healing. CONCLUSION: Combined
      660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers
      that failed to respond to other forms of treatment.

PMID- 19588537
TI  - Posttraumatic stress disorder symptoms in cancer: psychometric analysis of the
      Spanish Posttraumatic Stress Disorder Checklist-Civilian version.
AB  - OBJECTIVE: The PTSD Checklist-Civilian version (PCL-C) was used as a screening
      tool to assess the presence of PTSD symptoms. The aim of this study was to
      explore the factorial structure of the Spanish version of the PCL-C and calculate
      the correlation of PTSD symptoms with distress and health-related quality of
      life. METHOD: The sample included 494 cancer outpatients. In order to validate
      the PCL-C, a principal component analysis was applied. The association between
      variable was measured by Pearson correlation. RESULTS: Findings evidenced three
      symptoms clusters on the PCL-C version, defined as Hyperarousal/Re-experiencing,
      Numbing and Avoidance. About 10% of the total sample met clinical PTSD symptoms.
      In addition, PTSD symptoms were related negatively to health-related quality of
      life and positively related with distress. CONCLUSION: The conceptualization of
      PTSD symptoms for cancer patients is supported by the specific symptom clusters
      identified on PCL-C.

PMID- 19588539
TI  - Neuropsychological interventions for memory impairment   and the role of single
      case design methodologies.

PMID- 19588538
TI  - Systematic review of post-treatment psychosocial and behaviour change
      interventions for men with cancer.
AB  - OBJECTIVES: The psychosocial impacts of a cancer diagnosis include reduced
      quality of life, poorer inter-personal relationships, hopelessness and mental
      illness. Worse outcomes, including mortality rates have been found for single men
      with cancer compared with women and partnered men. The aim of this systematic
      review was to examine the effectiveness of post-treatment psychosocial and
      behaviour change interventions for adult men with cancer, in order to inform the
      development of an intervention. A focus on single men was intended. METHODS: Ten
      databases were searched via Ovid and Web of Science. Papers were systematically
      extracted by title, abstract and full paper according to the inclusion/exclusion
      criteria. Full papers were assessed by two authors. INCLUSION CRITERIA:
      participants at any stage of a cancer diagnosis, > or =50% male and aged 18+;
      psychosocial and/or behavioural post-treatment interventions, using any format; a
      one-three level of evidence. Couple/carer/family interventions were excluded.
      RESULTS: From 9948 studies initially identified, 11 were finally included in the
      review. They implemented cognitive behaviour therapy, hypnosis or
      psychoeducational interventions. All studies had some positive results, however,
      lack of reporting of intervention content and methodological issues limit the
      findings. No studies intervened with single men, and none provided comparative
      outcomes for marital status. CONCLUSIONS: Effectiveness of interventions was
      difficult to assess as, while all had benefits, their generalisability was
      limited due to methodological and reporting limitations. Improved reporting
      procedures are required to allow for replication.

PMID- 19588540
TI  - Compensating for anterograde amnesia: a new training method that capitalizes on
      emerging smartphone technologies.
AB  - Following a neuropathological event, individuals left with moderate-to-severe
      memory impairment are unable to reliably form new memories. The most common
      challenges involve the capacity to perform a task in the future and to
      consciously recall a recent event. Disruption of these memory processes leaves
      the individual trapped in the present, unable to stay on track, and alienated
      from ongoing events. Memory research has demonstrated that implicit memory is
      often preserved despite severe explicit memory impairment and that preserved
      memory systems can provide avenues for acquiring new skills and knowledge. A
      within-subject single-case A1-B1-A2-B2 experimental design was used to introduce
      an established theory-driven training program of technology use for individuals
      with moderate-to-severe memory impairment. We describe its application to
      enabling RR, an individual with memory impairment postcolloid cyst removal, to
      independently support her memory using a commercial smartphone. RR showed
      successful outcome on both objective and qualitative measures of memory
      functioning. Moreover, she demonstrated consistent and creative generalization of
      acquired smartphone skills across a broad range of real-life memory-demanding
      circumstances. Our findings suggest that individuals with moderate-to-severe
      memory impairment are able to capitalize on emerging commercial technology to
      support their memory.

PMID- 19588541
TI  - Lifetime consumption of alcoholic beverages and risk of 13 types of cancer in
      men: results from a case-control study in Montreal.
AB  - BACKGROUND: The aim of the study was to investigate the association between
      lifetime consumption of alcoholic beverages and cancer risk. METHODS: Data were
      collected in a population-based case-control study, conducted in Montreal in the
      mid-1980s, designed to assess the associations between hundreds of non
      occupational and occupational exposures and multiple cancer sites in men. We
      present results for 13 cancer sites: oesophagus (n = 78), stomach (n = 215),
      colon (n = 427), rectum (n = 239), liver (n = 28), pancreas (n = 83), lung (n =
      700), melanoma (n = 107), prostate (n = 374), bladder (n = 425), kidney (n =
      156), Hodgkin's lymphoma (n = 42), and non-Hodgkin's lymphoma (n = 190), in
      comparison to population controls (n = 507). Odds ratios (OR) were estimated for
      the associations between lifetime consumption of total alcoholic beverages, beer,
      wine, and/or spirits, altogether and separately, and each cancer site, while
      carefully adjusting for smoking and other covariates using polytomous logistic
      regression. RESULTS: For several cancers (oesophagus, stomach, colon, liver,
      pancreas, lung, prostate) there was evidence of increased risk among alcohol
      consumers compared with abstainers and occasional drinkers. For most sites, it
      was beer and to a lesser extent spirits consumption that drove the excess risks.
      CONCLUSIONS: Our results support the hypothesis that moderate and high alcohol
      intake levels over the lifetime might increase cancer risk at several sites.

PMID- 19588542
TI  - Epidemiology of primary brain tumors in the Middle Eastern population in
      California, USA 2001-2005.
AB  - BACKGROUND: The fast growing Middle Eastern (ME) population has rarely been
      studied in the U.S.. The purpose of this study was to compare the epidemiology of
      primary brain tumors in this ethnic population with the non-Hispanic, non-Middle
      Eastern White (NHNMW) in California. METHODS: ME cases were identified by surname
      in the California cancer registry and ME population estimates were based on
      ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant,
      16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425
      uncertain) in the NHNMW were available for this study. RESULTS: ME patients were
      significantly (p < 0.05) younger and their age-adjusted incidence rates per
      100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than
      similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant
      tumors were similar. Meningioma was the main histology responsible for the
      observed increase in patients over 40 years of age. Also increased were benign
      tumors of the pituitary and pineal glands. The overall mortality in patients with
      benign tumors was significantly lower than malignant tumors. CONCLUSIONS: This
      study presents a significantly high incidence of benign meningioma in the ME
      population in California. This may be due to higher susceptibility or exposure of
      this ethnic group to the risk factor(s) for this neoplasm. Considering the
      reported causal association of benign meningioma with childhood radiation
      exposure from Israel, exposure to this risk factor in this ethnic group needs to
      be evaluated in future studies.

PMID- 19588543
TI  - Vitamin D receptor gene polymorphism(s) and breast cancer risk in north Indians.
AB  - BACKGROUND: Vitamin D (1,25-dihydroxyVitamin D3) has shown experimentally
      anticarcinogenic effects and is thought to protect against breast cancer. The
      actions of Vitamin D are mediated via the Vitamin D receptor (VDR), and the
      polymorphisms at 3'UTR region of this gene are associated with the risk and
      progression of breast carcinoma. The current study is an attempt to examine the
      association of these variations with breast cancer risk in north Indians.
      METHODS: A total of 160 cases and 140 control subjects were studied for the
      polymorphisms at 3' end of the VDR gene. A polymerase chain reaction-based
      restriction fragment length polymorphism (PCR-RFLP) method and fragment analysis
      was performed to determine ApaI and TaqI polymorphisms and variable length poly-A
      microsatellite repeats. Linkage disequilibrium (LD) was calculated for each pair
      of polymorphisms. Unadjusted and adjusted odds ratios for breast cancer with
      genotypes comprising the polymorphic sites were calculated to understand their
      role towards breast cancer susceptibility. RESULTS: Patient's with long poly-A
      repeat showed a significant association with disease (chi 2 = 9.52, df = 2, P
      <or= 0.01). Compared to subjects having two S alleles (SS), odds ratios (and 95%
      CI) were 0.75 (0.45-1.23) and 2.49 (1.18-5.27) for subjects having genotypes SL
      and LL, respectively. Among matched pairs (age), the poly-A LL genotype was found
      significantly associated with increased risk of breast cancer among early-onset
      cases (P = 0.02). The unconditional logistic regression analysis demonstrated a
      significant association between grade and LL genotype [(unadjusted odds ratio
      (95% CI): 4.45 (1.87, 10.63); adjusted odds ratio: 4.66 (1.88, 11.53)]. No
      significant association was observed for the VDR ApaI (chi 2 = 1.00, df = 2, P =
      0.60) and TaqI polymorphism (chi 2 = 0.35, df = 2, P = 0.83). Although, strong LD
      was not observed among these polymorphic sites, it denies the total equilibrium
      at the same time. Based on haplotype distribution, the most common one observed
      among cases and controls was ATS while, genotype AATTLL had shown a significant
      association with the breast cancer risk (P = 0.02). CONCLUSIONS: The results
      indicate that the VDR poly-A polymorphism is significantly associated with breast
      cancer risk in north Indians especially with early onset disease. Although, ApaI
      and TaqI did not show any significant association with the disease when analyzed
      in isolation, but TaqI might modulate the risk associated with L alleles.
      Further, understanding the functional role of these variants residing on the VDR
      haplotype associated with disease susceptibility may suggest novel approaches for
      breast cancer prevention and therapy.

PMID- 19588544
TI  - Combined effect of NAT2, MTR and MTHFR genotypes and tobacco on bladder cancer
      susceptibility in Tunisian population.
AB  - BACKGROUND: Cigarette smoking is the predominant risk factor for bladder cancer.
      This risk may be modified by polymorphisms in carcinogens metabolism genes;
      including those involving the N-acetyl transferase 2 (NAT2) which have been
      correlated with decreased enzyme activities. Moreover, folate insufficiency can
      induces carcinogenesis by decreasing DNA methylation. Methylenetetrahydrofolate
      reductase (MTHFR) and methionine synthase (MTR) are enzymes that play central
      roles in the folate metabolic pathway. The MTHFR 677*T and MTR 2756*G variants
      are associated with decreased enzyme activity. METHODS: In this work, we have
      conducted a case-control study in order to assess the combined effect of tobacco,
      slow NAT2 variants, MTHFR 677*T and MTR 2756*G alleles on bladder cancer
      development in North Tunisia. RESULTS: For MTR A2756G, alleles and genotypic
      distributions differed significantly between cases and controls (p = 0.00009, OR
      = 3.27, CI 95% 1.76-6.12). While, in non-smokers patients the slow NAT2 did not
      appear to influence bladder cancer susceptibility; our results suggested that it
      might act with an additive contribution with tobacco as well as with that
      determined by MTR 2756 AG or 2756 GG genotypes (p = 0.0008). Identical cumulative
      effect was detected for slow NAT2 and MTHFR 677*T variant (p = 0.0003; OR = 36.6;
      CI 95% 3.4-935.3). CONCLUSION: The strongest result obtained by this study was
      for an additive effect between smoking status, slow NAT2 variants, MTR 2756*G and
      MTHFR 677*T alleles, in affecting bladder cancer risk.

PMID- 19588546
TI  - Melanoma metastasis to the breast: a diagnostic pitfall.
AB  - BACKGROUND: Breast metastasis is an extremely rare phenomenon. While nearly every
      malignancy has been described to metastasize to the breast; melanoma, lymphoma
      and leukemia tend to be the most common. Among these primary tumors, melanoma
      metastasis represents a diagnostic pitfall for both the clinicians and
      histopathologists. METHODS: We report a case of widely metastatic malignant
      melanoma with diagnostic difficulties in both clinical and histopathological
      evaluation. Thorax CT, Abdominal MRI, tumor marker screening and two biopsies
      were performed to conclude the primary. RESULTS: In clinical evaluation, there
      were rapidly proliferating multiple nodular lesions at the skin, breasts, lungs,
      ovaries and peritoneum accompanied by only increased CA 125 in tumor marker
      panel. The initial biopsy performed from a skin nodule was concordant with a
      metastatic carcinoma suggesting breast as the primary. The diagnosis was made by
      immunohistochemical staining of the second biopsy performed from a breast nodule.
      CONCLUSION: Although no strict clinical criteria exist to differentiate a
      melanoma metastasis to the breast from a primary breast carcinoma atypically
      rapid growth, normal Ca 15-3 level, and a history of prior melanoma may be
      helpful. However, it may be still misdiagnosed in some cases even
      histopathologically if the immunohistochemical staining is not performed.

PMID- 19588545
TI  - Development of a rat model by 3,4-benzopyrene intra-pulmonary injection and
      evaluation of the effect of green tea drinking on p53 and bcl-2 expression in
      lung carcinoma.
AB  - BACKGROUND: A convenient animal model of primary lung cancer is compelling for
      investigation into the disease mechanisms and for development of therapeutic
      strategies. This study aims to develop a reproducible rat model for lung
      carcinoma by intra-pulmonary injection of 3,4-benzopyrene, and to evaluate the
      preventive effect of green tea on the formation of lung carcinoma. METHODS:
      Sprague-Dawley rats of the same ages were randomly assigned into three groups
      treated differently. Rats in group one were given green tea in drinking water
      (tea concentration: 1.2%; tea polyphenols in the tea solution: 0.3%); rats in the
      groups two and three were given blank drinking water. Rats in the groups one and
      two were injected intra-pulmonarily with 3,4-benzopyrene dissolved in corn oil (2
      mg/0.2 mL/injection, fortnightly, 4 times in all); rats in the group three were
      injected with the vehicle corn oil as the control for injection. All the rats
      were sacrificed one year after the first intra-pulmonary injection. Tumors
      developed in rats and lung tissues were collected for carcinoma diagnosis and for
      p53 and bcl-2 expression. RESULTS: Intra-pulmonary injection of 3,4-benzopyrene
      steady induced lung carcinoma at a success rate of 75%. Administration with green
      tea drinking significantly reduced the incidence of lung carcinoma to 30%. Green
      tea up-regulated p53 expression in lung carcinoma, but significantly down
      regulated bcl-2 expression. CONCLUSIONS: Intra-pulmonary injection of 3,4
      benzopyrene can steady induce lung carcinoma in rats, and green tea has
      preventive effect against lung cancer possibly by regulating expression of some
      critical genes such as p53 and bcl-2.

PMID- 19588547
TI  - DNA-tumor virus entry--from plasma membrane to the nucleus.
AB  - DNA-tumor viruses comprise enveloped and non-enveloped agents that cause
      malignancies in a large variety of cell types and tissues by interfering with
      cell cycle control and immortalization. Those DNA-tumor viruses that replicate in
      the nucleus use cellular mechanisms to transport their genome and newly
      synthesized viral proteins into the nucleus. This requires cytoplasmic transport
      and nuclear import of their genome. Agents that employ this strategy include
      adenoviruses, hepadnaviruses, herpesviruses, and likely also papillomaviruses,
      and polyomaviruses, but not poxviruses which replicate in the cytoplasm. Here, we
      discuss how DNA-tumor viruses enter cells, take advantage of cytoplasmic
      transport, and import their DNA genome through the nuclear pore complex into the
      nucleus. Remarkably, nuclear import of incoming genomes does not necessarily
      follow the same pathways used by the structural proteins of the viruses during
      the replication and assembly phases of the viral life cycle. Understanding the
      mechanisms of DNA nuclear import can identify new pathways of cell regulation and
      anti-viral therapies.

PMID- 19588549
TI  - Review of companion animal viral diseases and immunoprophylaxis. Reply to Day et
      al.

PMID- 19588548
TI  - [Plea for the distinction between dark night and depression in the Johannes vom
      Kreuz sense. Comment on Kraetschmer K].

PMID- 19588550
TI  - Is getting influenza vaccine coverage data out during mid-season feasible?
      Evidence from a national survey of U.S. adults.
AB  - We demonstrated the feasibility of collecting and disseminating mid-season
      estimates of influenza vaccine coverage. We surveyed a nationally representative
      sample of U.S. adults (n = 3972) via the Internet about use of influenza
      vaccination as of mid-November 2008. Findings were presented on 10 December 2008
      to the media and the public health community during National Influenza Vaccine
      Week through a webinar sponsored by the National Foundation for Infectious
      Disease. Survey results suggested that just under 40% of adults with a specific
      vaccine indication had been vaccinated by mid-November and that 16% still
      intended to be vaccinated. Among those with the intention to be vaccinated,
      factors related to time and convenience were cited as reasons for not yet being
      vaccinated. If reported annually, national-level estimates of mid-season vaccine
      use could provide a benchmark against which to measure progress of strategies
      deployed at mid-season to improve influenza vaccination coverage.

PMID- 19588551
TI  - Phenylbutazone: back on the French market: reappearance. A NSAID to avoid. Life
      threatening toxicity.

PMID- 19588552
TI  - Glucosamine plus vitamin K antagonists: bleeding. One more reason to avoid using
      glucosamine.

PMID- 19588553
TI  - Tiotropium: stroke. Do not use this drug.

PMID- 19588554
TI  - Somatropin: tumours and diabetes. Indication challenged in idiopathic short
      stature.

PMID- 19588555
TI  - Neuroleptics: necrotising enterocolitis.
AB  - Both typical and atypical neuroleptics carry a risk of intestinal necrosis, a
      frequently fatal adverse effect. The risk is increased by co-administration of
      atropinic drugs.

PMID- 19588556
TI  - Trimetazidine: abnormal movements and hallucinations. Should be withdrawn from
      the market.

PMID- 19588557
TI  - Exenatide: pancreatitis. Gastrointestinal symptoms.

PMID- 19588558
TI  - Partial hospitalization versus day treatment.

PMID- 19588559
TI  - Rational fixed dose combinations (FDC) in India.

PMID- 19588560
TI  - Health maintenance organisation--a solution to Medicare of masses.

PMID- 19588561
TI  - [Uncertainties about the future of psychotherapy].

PMID- 19588563
TI  - Issue in honor of Professor George Smith, II.

PMID- 19588562
TI  - Kentucky's shortage of pediatric gastroenterologists affects health care for all
      children.

PMID- 19588564
TI  - Abstracts of the 16th World Congress of Disaster and Emergency Medicine, 12-15
      May 2009, Victoria, BC, Canada.

PMID- 19588566
TI  - [Abstracts of the Scientific Conference on Laboratory Diagnosis in Specialized
      and Emergency Care Health, April 1-2, 2008, Moscow].

PMID- 19588565
TI  - Hamlet's therapy.

PMID- 19588567
TI  - Robert Fludd's theory of geomancy and his experiences at Avignon in the winter of
      1601 to 1602.

PMID- 19588568
TI  - Doctor John Mitchell's yellow fever epidemics.

PMID- 19588569
TI  - Asia Pacific Clinical Nutrition Society Award for 2009.

PMID- 19588570
TI  - Some historical problems connected with the study of Egyptian mummies.
AB  - The present essay is intended to call attention to three problems or areas of
      investigation that are connected with the study of Egyptian mummies. In each
      instance a supply of evidence exists and more can probably be found; and in each
      area much could be learned from historical analysis of appropriate breadth and
      depth.

PMID- 19588571
TI  - A proposed alliance between the Order of Malta and the United States, 1794:
      suggestions made to James Monroe as American minister in Paris.

PMID- 19588572
TI  - International Conference on Harmonisation; guidance on Q8(R1) Pharmaceutical
      Development; addition of annex; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "Q8(R1) Pharmaceutical Development." The guidance was prepared
      under the auspices of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH
      Q8(R1) guidance includes the previously published parent guidance entitled "Q8
      Pharmaceutical Development" (Q8 parent guidance) (71 FR 29344; May 22, 2006) and
      a newly added annex. The annex provides further clarification of key concepts
      outlined in the Q8 parent guidance and describes the principles of quality by
      design (QbD). The annex is intended to show how concepts and tools (e.g., design
      space) outlined in the Q8 parent guidance could be put into practice by the
      applicant for all dosage forms.

PMID- 19588573
TI  - Lead in the bones of prehistoric lead-glaze potters.
AB  - In 1932 Haury described lead-glaze pottery from the Southwest. In view of his
      report, it appeared desirable to find out whether the makers of such pottery
      suffered from lead poisoning. A series of 46 bone specimens from Kinishba, where
      lead-glaze pottery was made, and a control series of 33 specimens from Point of
      Pines, where such pottery is not known to have been made, were screened by X-ray
      and by X-ray diffraction. The 11 most promising specimens were then analyzed by
      atomic absorbtion spectrophotometry. Lead was found in quantities believed to be
      below the toxic range; concentrations in the control series from Point of Pines
      were, with few exceptions, higher than in the experimental series from Kinishba.

PMID- 19588574
TI  - Imaging of somatostatin receptor subtype 2 in advanced hepatocellular carcinoma
      by 68Ga-DOTATOC PET.

PMID- 19588575
TI  - Medicaid program: rescission of School-Based Administration/Transportation final
      rule, Outpatient Hospital Services final rule, and partial rescission of Case
      Management Interim final rule. Final rule.
AB  - This rule finalizes our proposal to rescind the December 28, 2007 final rule
      entitled, "Elimination of Reimbursement under Medicaid for School Administration
      Expenditures and Costs Related to Transportation of School-Age Children Between
      Home and School;" the November 7, 2008 final rule entitled, "Clarification of
      Outpatient Hospital Facility (Including Outpatient Hospital Clinic) Services
      Definition;" and certain provisions of the December 4, 2007 interim final rule
      entitled, "Optional State Plan Case Management Services." These regulations have
      been the subject of Congressional moratoria and have not yet been implemented
      (or, with respect to the case management interim final rule, have only been
      partially implemented) by CMS. In light of concerns raised about the adverse
      effects that could result from these regulations, in particular, the potential
      restrictions on services available to beneficiaries and the lack of clear
      evidence demonstrating that the approaches taken in the regulations are
      warranted, CMS is rescinding the two final rules in full, and partially
      rescinding the interim final rule. Rescinding these provisions will permit
      further opportunity to determine the best approach to further the objectives of
      the Medicaid program in providing necessary health benefits coverage to needy
      individuals.

PMID- 19588576
TI  - Abstracts of the 5th Preventive Dental Conference, November 13-15, 2008,
      Budapest, Hungary.

PMID- 19588577
TI  - Medicaid program; health care-related taxes. Final rule.
AB  - This rule finalizes our proposal to delay enforcement of certain clarifications
      regarding standards for determining hold harmless arrangements in the final rule
      entitled, "Medicaid Program; Health Care-Related Taxes" from the expiration of a
      Congressional moratorium on enforcement from July 1, 2009 to June 30, 2010.

PMID- 19588578
TI  - Asthma: Insights and Expectations. Proceedings and abstracts of the Thomas L.
      Petty Aspen Lung Conference, June 4-7, 2008.

PMID- 19588579
TI  - Civilian Health and Medical Program of the Department of Veterans Affairs
      (CHAMPVA): preauthorization of durable medical equipment. Final rule.
AB  - This document amends the Department of Veterans Affairs (VA) medical regulations
      for the Civilian Health and Medical Program of the Department of Veterans Affairs
      (CHAMPVA) preauthorization section by increasing the dollar ceiling for purchase
      or rental of durable medical equipment (DME) from $300 to $2,000.

PMID- 19588580
TI  - Symmetrical osteoporosis (spongy hyperostosis) in a prehistoric skull from New
      Mexico.
AB  - Fragments of an Anasazi skull (Pueblo II-III) from New Mexico are described.
      Lesions of symmetrical osteoporosis were found and their anatomical and
      roentgenographic characteristics are discussed. The term symmetrical osteoporosis
      has led to confusion with the unrelated disease osteoporosis and should be
      replaced by the designation spongy hyperostosis.

PMID- 19588581
TI  - Prevention of Salmonella enteritidis in shell eggs during production, storage,
      and transportation. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule that requires
      shell egg producers to implement measures to prevent Salmonella Enteritidis (SE)
      from contaminating eggs on the farm and from further growth during storage and
      transportation, and requires these producers to maintain records concerning their
      compliance with the rule and to register with FDA. FDA is taking this action
      because SE is among the leading bacterial causes of foodborne illness in the
      United States, and shell eggs are a primary source of human SE infections. The
      final rule will reduce SE-associated illnesses and deaths by reducing the risk
      that shell eggs are contaminated with SE.

PMID- 19588582
TI  - Practical sports nutrition: survival nutrition by Burke Louise M.

PMID- 19588583
TI  - A study of Al-Samarqandi's medical writings with special emphasis on his book Al
      Asbab wa Al-'alamat (Causes and Symptoms), and Al-Kirmani's Sharh Al-Asbab wa Al
      'alamat (Commentary on Causes and Symptoms).

PMID- 19588584
TI  - George Gifford and Puritan witch beliefs.

PMID- 19588585
TI  - [Surgical treatment of the false aneurism of the gastroduodenal artery].

PMID- 19588587
TI  - [Favorable long-term follow up results of skin transplantation in the calcaneal
      area with the use of microvascular anastomoses].

PMID- 19588586
TI  - [Acute right ventricular perforation with the pacemaker electrode].

PMID- 19588588
TI  - [The spontaneous giant retroperitoneal hematoma].

PMID- 19588589
TI  - [Simultaneous three-valvular cardiac defect correction and hysterectomy].

PMID- 19588591
TI  - [The combined surgical treatment of the right atrial floating thrombus and
      hysteromyoma].

PMID- 19588590
TI  - Scientists and broad churchmen: an early Victorian intellectual network.

PMID- 19588592
TI  - Memoranda and documents: Doctor Douglass' "Summary": polemic for reform.

PMID- 19588593
TI  - The mediaeval medical school at Cambridge.

PMID- 19588594
TI  - A medical history of the later stages of the Atlanta campaign.

PMID- 19588595
TI  - The impact of the black death upon Sienese government and society.

PMID- 19588596
TI  - Report of the Poison Control Centre for the period 1 January-31 December 2008.

PMID- 19588599
TI  - Pox and politics in Marblehead, 1773-1774.

PMID- 19588597
TI  - Doctor Thomas Hamilton: two views of a gentleman of the Old South.

PMID- 19588600
TI  - Health promotion in the Pacific.

PMID- 19588601
TI  - It's all in.

PMID- 19588602
TI  - Dietary intake in infants and young children in the Marshall Islands.
AB  - Changes in traditional foodways associated with increasing modernization have
      affected the feeding patterns of infants and young children. Declines in the
      duration of exclusive breastfeeding have been associated with poor nutritional
      status and increased morbidity from infectious diseases. We conducted a cross
      sectional survey of dietary intake in children under six in four settings in the
      Republic of the Marshall Islands in Micronesia. The mean duration of
      breastfeeding in the sample was 11 months, however only 16% of subjects were
      exclusively breastfed for the first six months, which is recommended by the WHO,
      UNICEF and other policymakers. Among non-exclusively breastfed infants,
      supplemental foods were introduced as early as 2 months. Mean intakes for total
      energy, protein, carbohydrates, fat and iron were calculated for subjects
      providing recalls. Intake levels for energy, protein, carbohydrates and iron
      varied by location. Recommendations for future research and program intervention
      are outlined.

PMID- 19588603
TI  - Geriatric assessment during health promotional home visits by zone nurses of the
      Suva subdivision, Fiji.
AB  - The elderly population of Fiji is around 7% of the total national population and
      is predicted to increase to 23% in 2050, yet the country does not have a standard
      procedure that assesses their health and well-being. A survey was carried out to
      explore current Geriatric Assessment Practice (GAP) amongst the zone nurses of
      the Suva subdivision during health promotional home visits. Overall the GAP of
      nurses is poor. Nurses had little awareness of assessment procedures and they
      constitute. The lack of a standard geriatric assessment protocol that can be used
      by all zone nurses is evident. More research on the elderly should also be
      carried out to provide better information and improve nursing practice.

PMID- 19588604
TI  - Attempted suicide in Western Viti Levu, Fiji.
AB  - Case records were reviewed of 132 people referred to the FSEG in Lautoka from
      January 2004 to December 2005 following an attempt at suicide. Seventy five
      percent of the study group was under age 32, 90% were Indo-Fijian and 66% female;
      these characteristics were significantly overrepresented compared to the
      demography of the source population. Findings show that social stress constitutes
      the primary reason for attempted suicide among all ages, genders, religions and
      ethnicities and suggest that Fijians and Christians may also be reacting to
      economic factors. A control group study of non-suicidal persons under stress is
      needed to distinguish characteristics of suicide attempters. Our tentative
      findings agree with the current perception and literature on selective
      demographic risks for attempted suicide -- young age, Indian ethnicity, female
      gender and social stress.

PMID- 19588605
TI  - Masculinity, mental health and Violence in Papua New Guinea, Vanuatu, Fiji and
      Kiribati.
AB  - This paper presents the findings of a four country study conducted by the
      Foundation for the Peoples of the South Pacific-International through its
      affiliates in Fiji Vanuatu, Papua New Guinea and Kiribati to demonstrate the
      linkage between young men, mental health and violence in the Pacific. The
      findings common among the four studies arise from the sociocultural and economic
      transitions occurring across the Pacific Region, where recent years have shown
      that the Pacific lifestyle has become increasingly stressful and violent. Limited
      opportunity to participate in the modern lifestyle and its economy has led to
      personal mental stress, social exclusion, unemployment and the growth of a
      subgroup of disaffected young people, who resort to a range of means to acquire
      their daily needs and, among whom, the norms that govern the use of violence
      differ from those of the general community.

PMID- 19588606
TI  - A pilot food store intervention in the Republic of the Marshall Islands.
AB  - To improve diet and reduce risk for obesity and chronic disease, we developed,
      implemented and evaluated a pilot intervention trial with 23 large and small food
      stores in the Republic of the Marshall Islands (12 intervention, 11 control). The
      intervention included both mass media (radio announcements, newspaper ads, video)
      and in-store (cooking demonstrations, taste tests, shelf labeling) components.
      Consumer exposure to the mass media components was high (65% had heard half or
      more of the radio announcements, 74% had seen at least one of the newspaper ads).
      Consumer exposure to the in-store components of the intervention was moderate
      (61% attended at least one cooking demonstrations, 59% received at least one
      recipe card). After adjustment for age, sex and education level, increased
      exposure to the intervention was associated with higher diabetes knowledge
      (p<0.05) and label reading knowledge (p<0.05), but not with increased self
      efficacy for performing promoted healthy behaviors. The intervention was
      associated with increased purchasing of certain promoted foods (p<0.005),
      including oatmeal, turkey chili, fish, canned fruit and local vegetables. It was
      also associated with improvements in healthiness of cooking methods (p<0.05).
      Food store centered interventions have great potential for changing cognitive and
      behavioral factors relating to food choice and preparation, and may contribute to
      lessening the burden of diet-related chronic disease worldwide.

PMID- 19588607
TI  - Assessing overweight and obesity in American Samoan adolescents.
AB  - OBJECTIVE: A small number of informed Samoans question the relevance of applying
      standards developed primarily from Caucasian populations when screening
      Polynesian children for obesity. They attribute higher body mass index values in
      Polynesian populations, in part, to anatomical factors other than higher body fat
      percentage. METHODS: We attempted to allay these suspicions by assessing a sample
      of 380 American Samoan schoolchildren aged 11 to 18 for overweight and obesity
      using both the International Obesity Task Force and the Centers for Disease
      Control age- and sex-specific body mass index cutoffs and recently proposed age-
      and sex-specific waist circumference cutoffs for children and adolescents. We
      tested cholesterol and glucose levels for risk factors associated with obesity,
      and hemoglobin levels for iron deficiency. We also compared body mass index
      values from our sample with those from a similar sample taken in American Samoa
      in 1978 and 1982. RESULTS: Both body mass index cutoffs equally distinguished
      overweight or obese individuals, constituted by 62% of the males and 70% of the
      females, from individuals with normal weight. Waist circumference cutoffs
      assigned percentages of 56% and 61%, respectively. Applying BMI cutoffs to data
      collected a quarter century ago indicated that 23.0% of males and 43.5% of
      females were either overweight or obese. We failed to obtain evidence for
      elevated levels of cholesterol and glucose in overweight and obese individuals
      among 49 preprandial students. Six males and ten females had subnormal levels of
      hemoglobin but displayed no physical symptoms suggesting iron deficiency.
      CONCLUSION: The prevalence of overweight and obesity among contemporary American
      Samoan adolescents make them an especially vulnerable faction of the global
      obesity epidemic.

PMID- 19588608
TI  - Evolving directions in health promotion workforce development.
AB  - PROJECT CONTEXT: Leaders in the fields of public health and health promotion
      increasingly advocate a socio-ecological approach to meet contemporary and
      emerging population health challenges. It is essential that health promotion
      workforce development initiatives mirror the evolving direction of the field to
      facilitate translation of theory into practice. To date, there has been limited
      effort to map the socio-ecological approach into tertiary education curricula.
      PROJECT DESCRIPTION: This project was undertaken as part of the development
      process for an undergraduate health promotion degree in Queensland, Australia. A
      review of the health promotion workforce development literature was undertaken.
      Group processes, key informant interviews and a Delphi technique were used to
      engage health promotion academics and practitioners, including an International
      Health Promotion Expert Advisory Panel, and an Industry Advisory Group in
      defining the components of the program. FINDINGS: The consultative processes
      facilitated the development of an undergraduate health promotion degree program
      underpinned by the socio-ecological approach with strong emphases upon the
      processes or 'how you do it' of health promotion together with evidence-based
      decision making and practice. CONCLUSIONS: As the basis and practice of health
      promotion progresses toward a socio-ecological approach, workforce training needs
      to keep pace with these developments to ensure an appropriately skilled health
      promotion workforce to meet emerging population health challenges. The reported
      project and the degree program that has been developed is an example of one step
      towards achieving this important and necessary shift in health promotion
      workforce development in Australia.

PMID- 19588609
TI  - Towards prevention of breast cancer in the Pacific: influence of diet and
      lifestyle.
AB  - Breast cancer is a multifactorial disease which has created a significant health
      problem worldwide. The literature suggests that there is an increase the
      prevalence of breast cancer among the Pacific Islanders in the last two decades.
      Factors which influence breast cancer risk include gender, genetic mutation,
      diet, parity and endocrine. Nutritional studies and epidemiological surveys show
      that dietary and lifestyle factors play significant role in breast cancer risk.
      Breast cancer risk is reduced by regular intake of fruits, vegetables and omega-3
      fatty acids-rich diet. Whereas obesity, smoking, alcohol consumption and
      sedentary lifestyle increase breast cancer risk. Breast feeding practice is
      protective against breast cancer. Intensive awareness campaigns and public
      education are necessary to discourage risk behaviour among the Pacific Islanders.

PMID- 19588610
TI  - Nutrition communication in the Pacific.
AB  - This paper summarises the findings of a scoping study to analyse and guide
      nutrition communication in some countries in the Pacific region. Nutrition is
      fundamental to achieving good health and preventing the rising prevalence of non
      communicable disease. Dietary patterns are influenced by many factors and complex
      interactions, such as income, food prices, individual preference and beliefs,
      cultural traditions, as well as geographical, environmental and social factors.
      These interactions, the quantitative and qualitative changes in the diet, and the
      accompanying lifestyle changes seen in recent years, make a collaborative
      approach to behaviour change essential. This study suggests that by supporting
      nutritionists to promote nutrition, improve public awareness and by addressing
      key areas influencing nutrition communication, gains towards improving public
      health can be made at a regional level.

PMID- 19588611
TI  - Some lessons in tackling social determinants of health in resource-poor settings:
      health promotion with young people in Vanuatu.
AB  - Community based health promotion initiatives are recognised as important
      strategies to address the growing burden of non-communicable diseases in
      developing countries. However, limited knowledge exists on how such initiatives
      work in practice. One innovative health promotion program of work, the Pacific
      Action for Health Project, is working with young people and communities in the
      Pacific country of Vanuatu to offset the future effects of risk factors for these
      diseases, through optimising broad lifestyle and living conditions for the
      positive promotion of health. Recognising the established link between non
      communicable diseases and their social determinants, the Pacific Action for
      Health Project works with young people to address these determinants at the
      community level including, but not limited to, unemployment. This paper appraises
      the program based on a constructivist approach to data gathering and analysis,
      with observations made in the field subsequently interpreted through the health
      promotion literature on community empowerment. From the data collected, six
      themes emerged as key attributes through which the program achieved its planned
      outcomes. Subsequent analysis through the community empowerment literature,
      specifically 'dynamic continuum' models of community development, provided deeper
      analysis of the program's strategies and offered insight into how the literature
      on community empowerment may work in practice in a resource poor context. In
      addition to the development of locally specific empowerment measures as
      indicators for future program evaluation, further ethnographic work and
      participatory-action research approaches are encouraged to assist the future
      development of the program.

PMID- 19588612
TI  - Cultural democracy: the way forward for primary care of hard to reach New
      Zealanders.
AB  - The use of cultural democracy, the freedom to practice one's culture without
      fear, as a framework for primary care service provision is essential for improved
      health service in a multi cultural society like New Zealand. It is an effective
      approach to attaining health equity for all. Many successful health ventures are
      ethnic specific and have gone past cultural competency to the practice of
      cultural democracy. That is, the services are freely taking on the realities of
      clients without and malice from those of other ethnicities. In New Zealand the
      scientific health service to improve the health of a multi cultural society are
      available but there is a need to improve access and utilization by hard to reach
      New Zealanders. This paper discusses cultural democracy and provide example of
      how successful health ventures that had embraced cultural democracy were
      implemented. It suggests that cultural democracy will provide the intellectual
      impetus and robust philosophy for moving from equality to equity in health
      service access and utilization. This paper would provide a way forward to
      improved primary care utilization, efficiency, effectiveness and equitable access
      especially for the hard to reach populations. use the realities of Pacificans in
      New Zealand illustrate the use of cultural democracy, and thus equity to address
      the "inverse care law" of New Zealand. The desire is for primary care providers
      to take cognizance and use cultural democracy and equity as the basis for the
      design and practice of primary health care for the hard to reach New Zealanders.

PMID- 19588613
TI  - Building the capacity of Fijian communities to improve health outcomes.
AB  - The purpose of this paper is to describe the experiences of building capacity
      toward improved health outcomes in a rural Fijian community. The paper defines
      the concept of community capacity situating this within the context of health
      programming. The tension that exists between the two key forms of health
      programming, top-down and bottom-up, is also discussed in terms of its resolution
      through the approach of 'parallel-tracking'. A practical means of visually
      representing the concept of community capacity is given using the spider-web
      configuration. The paper will be of interest to the planners and evaluators of
      health programmes that aim to build and measure community capacity.

PMID- 19588614
TI  - The concept of health promotion in Fiji.
AB  - INTRODUCTION: This paper sets out to describe stakeholders' views of the concept
      of health promotion in Fiji. METHOLODOLOGY: Sixty-one semi-structured qualitative
      interviews were carried out with participants from all levels of the health
      sector (National, Divisional, Sub-Divisional and zonal) as well as community
      members and other sectors that had an involvement in health promotion. Data
      collected was analysed using grounded theory following the process outlined by
      Strauss and Corbin. RESULTS: Participants described a concept of health promotion
      in Fiji that provides a sophisticated and effective framework for action to
      improve health. The immediate implication of this paper is that participants view
      the processes and structures for health promotion in Fiji as currently
      insufficient to fully implement the concept of health promotion articulated. In
      particular, the call for health promotion to be at the center of development is
      not matched by the action required at a regional and national level, the building
      of staff and community capacity is often ineffective in its current sporadic and
      intermittent form and the reorientation of the health sector has been hampered by
      the perception of the health sector as service providers rather than
      facilitators. CONCLUSION: To fully implement the concept of health promotion in
      Fiji, more attention needs to be given to the processes and structures that
      direct and support health promotion action. Specifically, there is a need to
      develop implementation strategies that provide required and timely inputs during
      the development and ongoing implementation of health promotion activity. This can
      be achieved by engaging relevant sectors, investing sufficient time and resources
      into building staff and community capacity and better defining responsibilities.

PMID- 19588615
TI  - A proposed future for the care, treatment and rehabilitation of mentally ill
      people in Fiji.
AB  - Admission to Fiji's sole psychiatric hospital St Giles attaches the stigma of
      mental illness to patients, which may impact on the course of their lives and on
      their social acceptability. We argue that alternatives to hospitalization are
      health promoting in that they avoid stigmatization and institutional dependency.
      Recommendations are proposed for the further development of a community-based
      mental health service, such that admission is avoided where possible and where
      services are provided in the least restrictive environment close to patient's
      family and community supports.

PMID- 19588616
TI  - Pacific issues of biodiversity, health and nutrition.
AB  - Neglect of traditional food systems has led to serious nutrition and health
      problems throughout the Pacific Islands. At the same time, there is concern about
      the loss of traditional knowledge, customs and culture related to local foods,
      and of biodiversity. However, there is still a great diversity of nutrient-rich
      local food crops in the Pacific, along with considerable knowledge about these
      foods, their methods of production, harvesting, storage, and preparation. An
      integrated approach is needed in order to make a meaningful impact on increased
      production, marketing/processing and use of local food crops and foods for better
      health and nutrition, requiring greater collaboration between the health sector
      and agencies in other sectors. Priorities for action include: documentation and
      assessment of traditional food systems, including analysis of local foods and
      crop varieties for their nutrient content; innovative means of increasing
      awareness of the values of local foods among the general public and policy
      makers; conservation of rare varieties of crops and food trees and protection of
      the environment; and an increased focus on small-scale processing and marketing
      of local foods. Overriding all of this is the urgent need to mainstream
      consideration of these important issues into relevant national and regional
      policies. The rubric "Biodiversity for Health and Nutrition" incorporates all of
      these issues and provides a framework within which all partner agencies can be
      involved.

PMID- 19588617
TI  - Reducing tobacco-related harm in the Pacific.
AB  - Tobacco use is a significant public health issue for the Pacific. Although
      Pacific Countries recognise this fact, their ability to respond is hampered by a
      lack of resources. The New Zealand Agency for International Development (NZAID)
      Tobacco Control in the Pacific Project was launched in 2004 to help address this
      resource gap and to support the tobacco control work currently under way in six
      Pacific countries. The project aims to create a sustainable Pacific approach to
      tobacco control and supplements the support provided by the World Health
      Organization, the Secretariat of the Pacific Community, and others in the
      important field of tobacco control. The project uses a comprehensive approach to
      tobacco control focusing on creating tobacco control action plans for each
      country, helping with the preparation and passage of tobacco control legislation,
      non-government organization capacity building, health promotion and assistance
      with smoking cessation activities.

PMID- 19588618
TI  - The role of policy in health promotion -- Fiji.
AB  - Our health is impacted by many sectors. The improvement of population health and
      productivity requires a broad understanding of human ecology and the social
      determinants of our health. Influencing change across many sectors requires a
      level of expertise that is currently missing from Pacific health systems --
      policy advocacy. National health promotion councils or coordinating bodies need
      to work across and within many sectors -- not only the health sector -- to bring
      about wide-ranging changes to our civil and social arrangements.

PMID- 19588619
TI  - From 'what' to 'how' -- capacity building in health promotion for HIV/AIDS
      prevention in the Solomon Islands.
AB  - This paper describes a capacity building process undertaken within the HIV/AIDS
      prevention project of the Adventist Development and Relief Agency (ADRA) in the
      Solomon Islands. ADRA HIV/AIDS has recently reoriented its project structure,
      moving beyond its awareness raising approach to incorporate health promotion
      frameworks, theories, strategies and assumptions. These have been used to inform
      project practice in project planning, delivery and evaluation. This paper shares
      what has worked and not worked in the capacity building process, including a
      project evaluation of the initial HIV/AIDS awareness raising project and the
      application of a number of capacity building strategies, including utilising a
      volunteer Australian Youth Ambassador for Development (AYAD) funded by the
      Australian Agency for International Development (AusAID). Existing and new
      projects are outlined. The underlying theme is that any capacity building
      exercise must include structural support (e.g. management, national frameworks)
      to ensure the incorporation of new initiatives and approaches. With time this
      enables ownership by counterparts and external partnerships to develop. The
      presence of an AYAD volunteer has been an effective strategy to achieve this.
      Reflections from the evaluators, the AYAD volunteer and the HIV/AIDS team are
      included.

PMID- 19588620
TI  - Putting the community at the center of measuring change in HIV prevention in
      Papua New Guinea: the Tingim Laip (Think of Life) Mobilisation.
AB  - This paper describes the national Tingim Laip (Think of Life) Mobilisation for
      HIV prevention that began in Papua New Guinea (PNG) in early 2005 and is funded
      by Australian Agency for International Development (AusAID) in cooperation with
      National AIDS Council. The Tingim Laip Mobilisation is a new and innovative
      intervention addressing the HIV and AIDS continuum through social mobilisation in
      34 high risk settings throughout PNG. The paper describes (i) the principles and
      process of the Tingim Laip intervention, (ii) the participatory monitoring and
      evaluation mechanisms, and (iii) outlines some of the preliminary findings and
      outcomes of the intervention. The Tingim Laip mobilisation after one year of
      implementation is showing encouraging evidence of contributing to knowledge,
      attitude, and behavioural change in the epi-center of the epidemic in PNG.

PMID- 19588621
TI  - The Pacific OPIC Project (Obesity Prevention in Communities) -- objectives and
      designs.
AB  - BACKGROUND: Evidence on how to reduce the increasing prevalence of youth obesity
      is urgently needed in many countries. The Pacific OPIC Project (Obesity
      Prevention In Communities) is a series of linked studies in four countries (Fiji,
      Tonga, New Zealand, Australia) which is designed to address this important
      problem. OBJECTIVES: The studies aim to: 1) determine the overall impact of
      comprehensive, community-based intervention programs on overweight/obesity
      prevalence in youth; 2) assess the feasibility of the specific intervention
      components and their impacts on eating and physical activity patterns; 3)
      understand the socio-cultural factors that promote obesity and how they can be
      influenced; 4) identify the effects of food-related policies in Fiji and Tonga
      and how they might be changed; 5) estimate the overall burden of childhood
      obesity (including loss of quality of life); 6) estimate the costs (and cost
      effectiveness) of the intervention programs, and; 7) increase the capacity for
      obesity prevention research and action in Pacific populations. DESIGN: The
      community studies use quasi-experimental designs with impact and outcome
      assessments being measured in over 14,000 youth across the intervention and
      control communities in the four sites. The multi-strategy, multi-setting
      interventions will run for 3 years before final follow up data are collected in
      2008. The interventions are being informed by socio-cultural studies that will
      determine the family and societal influences on food intake, physical activity
      and body size perception. PROGRESS AND CONCLUSIONS: Baseline studies have been
      completed and interventions are underway. Despite the many challenges in
      implementing and evaluating community-based interventions, especially in the
      Pacific, the OPIC Project will provide rich evidence about what works and what
      does not work for obesity prevention in youth from European and Pacific
      backgrounds.

PMID- 19588622
TI  - The Pacific OPIC Project (Obesity Prevention in Communities): action plans and
      interventions.
AB  - BACKGROUND: The Pacific OPIC Project (Obesity Prevention In Communities) includes
      whole-of-community intervention programs in four countries (Fiji, Tonga, New
      Zealand, Australia) aimed at reducing the prevalence of overweight and obesity in
      youth. DEVELOPMENT OF ACTION PLANS: At each intervention site, preliminary
      interviews were conducted with youth to identify the potential socio-cultural
      barriers and facilitators to healthy eating and regular physical activity in
      order to attain and sustain a healthy body size. This and other information was
      presented at a 2-day workshop with community stakeholders, including youth. The
      participants then prioritised the components for a draft action plan which was
      later consolidated through further community consultation. ACTION PLAN
      OBJECTIVES: Each action plan had two overall aims: to build community capacity
      and to promote healthy weight. The first three objectives in each action plan
      were on capacity building, social marketing messages, and evaluation. Next were a
      set of four to five behavioural objectives with associated strategies involving
      programs, events, social marketing and environmental change. Lastly, each site
      had one or two innovative or developmental objectives. PROGRESS: Interventions
      began in all sites from 2005, with the action plans guiding implementation
      priorities. The initial behavioural objective for targeting in Fiji was eating
      regular breakfast and meals throughout the day, for Tonga it was physical
      activity, and for Australia and New Zealand it was increasing water consumption
      and decreasing consumption of sweet drinks. CONCLUSIONS: The action plans have
      provided the basis for community engagement in the project, the guide to the
      implementation of activities and the template for the evaluation plan.

PMID- 19588623
TI  - Most significant change technique in the Pacific.

PMID- 19588624
TI  - Quit Victoria's smoking cessation training at the local, national and
      international level.

PMID- 19588625
TI  - Pacific circumcision of boys.

PMID- 19588626
TI  - Address by Dr. APJ Abdul Kalam during the inaugural function of Centenary
      Conference of the Trained Nurses' Association of India, Mumbai.

PMID- 19588627
TI  - Presidential address by Mr. Arvind B. Kulkarni, President TNAI at the Centenary
      Conference: 4-7 November 2008 Sri Shanmukhanand Auditorium, Sion, Mumbai.

PMID- 19588628
TI  - Nursing challenging in changing health care environment (scientific session-I).

PMID- 19588629
TI  - Nursing in the new world of health care: a vision (scientific session-II).

PMID- 19588630
TI  - Take steps now to reduce readmissions, ED visits within 30 days.

PMID- 19588632
TI  - Community CMs bridge gaps in the continuum.

PMID- 19588631
TI  - CMs help the chronically ill stay out of the hospital.

PMID- 19588633
TI  - Heart failure advocates help patients comply.

PMID- 19588634
TI  - Study shows readmissions drop when patients understand discharge instructions.

PMID- 19588635
TI  - ED triage improves patient flow.

PMID- 19588636
TI  - Strategies to increase your preauthorizations.

PMID- 19588637
TI  - Pathogenesis of acne vulgaris: recent advances.
AB  - Acne vulgaris is the most common disorder seen in ambulatory dermatology
      practice. Acne causes significant morbidity and the direct costs associated with
      it exceed $2.2 billion per year in the United States (U.S.). The pathogenesis is
      multifactorial, and our understanding of the mechanisms involved in the
      development of acne lesions has improved with time. Follicular
      hyperkeratinization, sebum production, presence of Propionibacterium acnes (P.
      acnes), inflammatory mediators, and androgens have been identified as key
      components of acne pathophysiology. Recent advances have been made in this area
      with the discovery of P. acnes interaction with Toll-like receptors (TLRs),
      vaccines targeting P. acnes or its components, antimicrobial peptides and the
      role of hormones.

PMID- 19588638
TI  - Comparative efficacy and safety results of two topical combination acne regimens.
AB  - Combination therapy has become the standard for the management of acne,
      particularly for moderate-to-severe cases. Among these combinations, those
      regimens containing benzoyl peroxide (BPO), clindamycin and a retinoid have been
      used frequently as they address most aspects of acne pathogenesis. This study
      compares the efficacy and safety of two common topical treatment regimens in the
      treatment of a moderate to severe facial acne vulgaris: fixed-combination gel
      containing BPO 5% and clindamycin 1% (BPO/C) plus tretinoin microsphere gel 0.04%
      (RAM) versus a regimen of a fixed-combination gel containing clindamycin
      phosphate 1.2% and tretinoin 0.025% (CPT) plus a once-daily BPO 5% wash. While
      both regimens were safe and effective, regimen BPO/C+RAM yielded a more rapid
      onset of effect versus regimen CPT+BPO against both non-inflammatory and
      inflammatory lesions. Both treatment regimens were well-tolerated.

PMID- 19588639
TI  - The development and optimization of a fixed combination of clindamycin and
      benzoyl peroxide aqueous gel.
AB  - Fixed combination products of clindamycin 1% (as 1.2% clindamycin phosphate) and
      benzoyl peroxide (BPO) 5% are commonly used in the treatment of acne vulgaris.
      Although any given topical acne product may be therapeutically effective, signs
      and symptoms of cutaneous tolerability may lead to missed applications by the
      patient, thus limiting adherence to therapy. BPO and other formulation components
      such as surfactants, preservatives and high levels of organic solvents can cause
      cutaneous irritation and dryness. BPO irritation is dose-dependent. An approach
      to optimizing the BPO concentration was undertaken to develop a surfactant- and
      preservative-free, clindamycin and low concentration (<5%) BPO formulation. A 33%
      reduction in skin irritation was seen when the BPO concentration was halved from
      5% to 2.5% (clindamycin-BPO 2.5% gel), maintaining a comparable amount of total
      BPO delivered to the skin. As a result, clindamycin-BPO 2.5% gel appears to
      provide efficacy comparable to that of higher concentration (5%) fixed
      clindamycin-BPO combination products and should optimize patient compliance as a
      result of the reduction in cutaneous tolerability reactions, including signs of
      skin irritation or dryness. Clinical studies have shown clindamycin-BPO 2.5% gel
      to be highly effective with the potential for a more favorable tolerability
      profile compared to products containing higher concentrations of BPO.

PMID- 19588640
TI  - A multicenter study of topical azelaic acid 15% gel in combination with oral
      doxycycline as initial therapy and azelaic acid 15% gel as maintenance
      monotherapy.
AB  - This two-phase, multicenter study was undertaken to examine the safety and
      efficacy of combination therapy with oral doxycycline and topical azelaic acid
      (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the
      effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the
      initial open-label, non-randomized phase of the study, subjects (n=172) received
      topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or =
      12 weeks. In the second, double-blind study phase, subjects who had initially
      undergone at least four weeks of combination treatment in phase 1 and who
      achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized
      to receive either AzA 15% gel or its vehicle twice daily for an additional 24
      weeks. Assessments of efficacy were obtained at four-week intervals throughout
      both phases of the study and included change in inflammatory lesion count,
      investigator global assessment (IGA) of rosacea severity, and separate
      assessments of erythema and telangiectasia severity. At the last visit for each
      phase of the study, the investigator and participant each rated overall
      improvement, with the participant rating cosmetic acceptability and the
      investigator rating treatment as "success" or "failure" based on IGA score.
      During the second phase of the trial, the rate of relapse -- defined as either a
      50% deterioration in the lesion count improvement from phase 1, an increase in
      erythema intolerable to the subject or maintenance therapy failure as judged by
      the investigator and/or the subject -- was obtained. Safety assessments were
      conducted for both phases of the study and included analysis of adverse events
      (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the
      open-label phase of the study, 81.4% of subjects had reached a 75% or greater
      reduction in inflammatory lesion count, and 64% of patients achieved treatment
      success. During the second study phase (maintenance phase), AzA 15% gel
      consistently provided a better maintenance response than vehicle, with
      maintenance of remission in 75% of patients over the six-month duration of the
      maintenance phase. Additionally AzA 15% gel showed a statistically significantly
      lower deterioration in absolute inflammatory lesion counts than did vehicle after
      8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs
      were encountered in the study, and 98.5% of subjects were satisfied with the
      local tolerability of both AzA gel and vehicle.

PMID- 19588641
TI  - Tretinoin microsphere gel pump 0.04% versus tazarotene cream 0.05% in the
      treatment of mild-to-moderate facial acne vulgaris.
AB  - This 12-week, single-center, investigator-blinded, randomized, parallel-design
      study assessed the safety and efficacy of tretinoin microsphere gel 0.04%
      delivered by pump (TMG PUMP) to tazarotene cream 0.05% (TAZ) in mild-to-moderate
      facial acne vulgaris. Efficacy measurements included investigator global
      assessment (IGA), lesion counts, and subject self-assessment of acne signs and
      symptoms. Efficacy was generally comparable between treatment groups, although
      TMG PUMP provided more rapid results in several parameters. IGA showed a more
      rapid mean change from baseline at week 4 in the TMG PUMP group (-0.18 versus 
      0.05 in the TAZ subjects). TMG PUMP yielded more rapid improvement in papules. At
      week 4, the mean percentage change from baseline in open comedones was
      statistically significant at -64% in the TMG PUMP group (P=0.0039, within group)
      versus -19% in the TAZ group (not statistically significant within the group;
      P=0.1875). Skin dryness, peeling and pruritus were significantly less in the TMG
      PUMP group as early as week 4. Adverse events related to study treatment were
      rare in both groups and all resolved upon discontinuation of study medication.

PMID- 19588642
TI  - Advancement in benzoyl peroxide-based acne treatment: methods to increase both
      efficacy and tolerability.
AB  - BACKGROUND: Antibiotic resistance of Propionibacterium acnes (P. acnes) is a
      growing phenomenon in the wake of widespread use of topical and systemic
      antibiotics for acne vulgaris. Benzoyl peroxide has a proven track record of
      safety and efficacy, and can decrease reliance on antibiotics in the treatment of
      acne. PURPOSE: To review the literature for methods to increase the efficacy and
      tolerability of benzoyl peroxide (BPO). METHODS: A PubMed literature search was
      done using the terms "benzoyl peroxide," "vehicle," "mechanism," and "delivery
      system." Relevant papers were reviewed for methods of increasing BPO efficacy and
      tolerability. RESULTS: BPO in concentrations of 2.5%, 5% and 10% are equally
      effective at treating inflammatory acne. However, higher concentrations are
      associated with more adverse effects. The efficacy of BPO may be enhanced by the
      presence of Vitamin E and tertiary amines. BPO is also more efficacious if used
      in combination with topical retinoids than as a monotherapy. Novel vehicles
      including a microparticle delivery system and those with a hydrophase or urea
      base increase the tolerability of BPO without sacrificing efficacy. CONCLUSION:
      Benzoyl peroxide has a proven track record of safety and efficacy for the
      treatment of acne. Recent discoveries have provided new methods of increasing the
      efficacy and tolerability of topical BPO, making it useful as monotherapy for
      mild acne or as an adjunct in the treatment of moderate to severe acne vulgaris.

PMID- 19588643
TI  - Anti-inflamatory dose doxycycline in the treatment of rosacea.
AB  - Anti-inflammatory dose doxycycline (ADD), which is the administration of
      doxycycline 40 mg extended-release capsule once daily, is the only oral therapy
      approved by the United States Food and Drug Administration (FDA) for treatment of
      rosacea. ADD once daily has been shown to exhibit anti-inflammatory activity
      while not demonstrating evidence of antibiotic effects, including with chronic
      administration. This article summarizes the clinical studies to date on the use
      of ADD once daily in papulopustular rosacea, including both monotherapy and
      combination therapy studies. The combination therapy approach of ADD once daily
      and metronidazole gel 1% once daily has been shown to exhibit a more rapid onset
      of therapeutic effect than topical therapy alone. ADD once daily has been
      demonstrated to be effective in adult subjects with moderate to severe rosacea,
      and exhibits a favorable safety profile coupled with absence of antibiotic
      selection pressure. Additionally, a much lower incidence of gastrointestinal side
      effects has been noted with ADD once daily as compared to doxycycline 100 mg once
      daily.

PMID- 19588644
TI  - Treatment of acne vulgaris using blue light photodynamic therapy in an African
      American patient.
AB  - BACKGROUND: Studies indicate photodynamic therapy is an effective treatment of
      inflammatory acne lesions on patients with Fitzpatrick skin types 1-3. There is a
      lack of evidence in the literature regarding the use of photodynamic therapy to
      treat acne vulgaris in African American patients. This article reports the first
      case of blue light photodynamic therapy to treat moderate inflammatory facial
      acne on an African American patient with type 5 skin. OBSERVATIONS: This article
      describes a 26-year-old African American woman with moderate inflammatory facial
      acne vulgaris. On examination, she had over 15 inflammatory papules on her face
      and post-inflammatory hyperpigmentation. The patient had a history of treatment
      failure with the following therapies: topical benzoyl peroxide, topical
      antibiotics, topical retinoids and oral antibiotics. At presentation, the patient
      was using a combination topical benzoyl peroxide/clindamycin product in the
      morning and tazoratene gel in the evening without success. The patient was
      treated with 20% aminolevulinic acid/blue-light photodynamic therapy spaced
      monthly for a total of four treatments, a once-daily application of hydroquinone
      4% cream and her existing topical regimen. The patient reported significant
      improvement of inflammatory acne lesions and post-inflammatory hyperpigmentation
      following two treatments with photodynamic therapy and was virtually clear of all
      acne lesions after the third treatment. CONCLUSION: Photodynamic therapy is an
      emerging remedy for patients with acne vulgaris resistant to standard treatment,
      particularly in patients with skin of color who are more sensitive to post
      inflammatory hyperpigmentation. In this African-American patient, 20%
      aminolevulinic acid/blue-light photodynamic therapy was effective in treating
      facial acne vulgaris.

PMID- 19588645
TI  - Beyond tretinoin: cosmeceuticals for aging skin.
AB  - In contrast to youthful skin, mature skin undergoes well-established clinical and
      microscopic changes, particularly after menopause. In particular, dermal
      thinning, loss of dermal collagen and decreased lipid production are complicated
      by the effects of life-long sun exposure. These changes manifest as wrinkling,
      loss of elasticity, dryness and textural changes that characterize mature skin.
      To effectively combat these age- and sun-related changes, a multifaceted approach
      is required. Any treatment for mature skin must address the many causes of skin
      changes, that is, collagen production, lipid balance and epidermal texture.
      Several currently available compounds have scientifically-established effects on
      skin, and are anticipated to be even more effective in combination. Women
      worldwide struggle with coming to terms with their aging skin, and seek ways to
      preserve its youthful appearance. While dermatologists' offices may offer
      tretinoin cream (Renova and related products), laser resurfacing approaches,
      volume fillers and Botox, demand also exists for topical products that preserve
      and improve skin tone. With the push toward "natural," "organic" and "herbal"
      products, public and private research has never generated more evidence for
      complementary therapy. During skin aging, and particularly menopause,
      characteristic changes occur. Topical compounds can target many aspects of the
      aging process. The following is a review of topical compounds that may help with
      particular parts of this process. How can different problems be approached? In
      addition to prescription approaches and physical modalities, several topical
      compounds, many available over the counter, show evidence for helping aged and
      photo-damaged skin. Clinical data exist for many of these compounds, and is
      divided by mechanism of action.

PMID- 19588646
TI  - Fatty liver-seat of insulin resistance.

PMID- 19588647
TI  - Non-alcoholic fatty liver disease (NAFLD)--the hepatic component of metabolic
      syndrome.
AB  - AIMS: To study the prevalence of NAFLD in those patients attending the routine
      health checkup and to establish a relationship between NAFLD and metabolic
      syndrome. PATIENTS AND METHODS: All patients attending the health check-up had
      their blood pressure, height and weight, waist circumference measurements, blood
      sugars, lipid levels and ultrasound abdomen done. The prevalence of NAFLD among
      these subjects was determined and the presence of risk factors for metabolic
      disease in each individual was analysed. A relationship between NAFLD and
      metabolic syndrome was then established. RESULTS: Of the 1003 people 225 (22.6%)
      had NAFLD with higher prevalence among males 164/565 (29%) than among females
      61/438 (13.9%). In the NAFLD group normal body mass index (BMI) was present in
      only 49/225 (20%) of the subjects while 119/225 (52.8%) were overweight and
      56/225 (24.8%) were obese. Though liver enzymes were normal the mean AST among
      cases was 37.41 +/- 14.50 and 33.93 +/- 14.15 among controls and the mean ALT was
      38.74 +/- 17.96 among cases and 31.62 +/- 13.49 among controls. Prevalence of
      metabolic syndrome was 106/225 (47%) among cases and 179/778 (23%) among
      controls. CONCLUSION: A diagnosis of fatty liver on ultrasound in an asymptomatic
      person should alert us of metabolic syndrome and its progression to
      cardiovascular disease. NAFLD may be considered as the hepatic component of
      metabolic syndrome.

PMID- 19588648
TI  - Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is commonly associated with
      type 2 diabetes mellitus (DM) though its prevalence is not well studied. We
      conducted a prospective study of prevalence and risk factors of NAFLD in patients
      with type 2 diabetes. RESEARCH DESIGN AND METHODS: 204 type 2 DM patients
      attending an out-patient diabetic clinic underwent abdominal sonography. Ninty of
      127 patients with fatty infiltration on ultrasound consented for liver biopsy,
      clinical and biochemical workup. RESULTS: Eighty seven percent had NAFLD on
      histology with 62.6% steatohepatitis and 37.3% fibrosis. Age, duration of
      diabetes mellitus, degree of glycemic control, body mass index, waist
      circumference, family history of diabetes mellitus, did not predict the presence
      or severity of NAFLD or fibrosis. Serum alanine aminostranferase (ALT) and
      alkaline phosphatase levels, though within normal limits, were significantly
      higher in patients with steatohepatitis. Prevalence of NASH increased with
      increase in the components of the metabolic syndrome. Serum AST/ALT ratio were
      also significantly higher (p-0.049) in patients with severe fibrosis. All
      patients with severe fibrosis had metabolic syndrome. CONCLUSIONS: Prevalence of
      NAFLD and NASH in our cohort of type 2 DM patients is high and increases with
      multiple components of metabolic syndrome. NASH and advanced fibrosis can occur
      in diabetic patients without any symptoms, signs or routine laboratory test
      abnormalities.

PMID- 19588649
TI  - Gitelman's syndrome.
AB  - We report a case of 30 year old male who presented with alleged history of
      consumption of organophosphorus compound. During stay in hospital, he was found
      to be persistently hypokalemic and low in magnesium. Subsequently with detailed
      clinical and laboratory evaluation, he was diagnosed to be having Gitelman's
      syndrome. He was discharged on potassium and magnesium supplements along with
      potassium sparing diuretics.

PMID- 19588650
TI  - Rifampicin-induced thrombocytopenia.

PMID- 19588651
TI  - James Black & birth of beta blockers.

PMID- 19588652
TI  - Camphor ingestion: an unusual cause of seizure.

PMID- 19588653
TI  - Self esteem -- its role in nursing education & practice.

PMID- 19588654
TI  - Cabbage leaves vs hot and cold compresses in the treatment of breast engorgement.
AB  - This study was conducted to evaluate the effect of cold cabbage leaves and
      alternate hot and cold compresses in decreasing breast engorgement and pain in
      post-natal mothers admitted in AIIMS, New Delhi.

PMID- 19588655
TI  - Brain death and organ donation.

PMID- 19588656
TI  - Systems theory in nursing education.

PMID- 19588657
TI  - Developing performance appraisal tool for staff nurses.

PMID- 19588658
TI  - Juvenile diabetes mellitus.

PMID- 19588659
TI  - Courage and character, leaders and legends: an interview with Leonard Bailey, MD.
      Interview by Linda Ohler.

PMID- 19588660
TI  - The kidney transplant failure experience: a longitudinal case study.
AB  - PURPOSE: To explore participants' experiences of kidney transplant failure.
      BACKGROUND: Kidney transplants are effective and efficient but not without
      complications. About 7% to 12% of kidney transplants fail within a year, and
      rates of failure increase over time. Graft failure can have profound effects,
      often resulting in depression and, occasionally, suicidal feelings. Despite these
      issues, the personal dimensions of graft failure have been poorly researched.
      METHODS: One donor-recipient couple experienced irreversible graft rejection
      immediately after a kidney transplant. This article is a longitudinal case study
      of this family's experiences. Data were collected through 3 semistructured
      interviews, conducted before the transplant and at 3 and 10 months after the
      transplant. Interviews were recorded, transcribed verbatim, and data coded into
      categories arising from the participants' accounts. RESULTS: Transplantation
      represented a significant source of hope. Fear of transplant failure was a major
      concern, but was dealt with by using emotion-focused coping mechanisms. Graft
      rejection was devastating, causing feelings of grief, loss, suicide, and
      depression. Depression improved as physical health and a sense of personal
      control improved. The recipient felt inadequately prepared for graft failure and
      poorly supported by health professionals. CONCLUSION: The primary source of grief
      and depression appeared to be related to the recipient's "loss of imagined
      future" (ie, the life that she anticipated after transplant). Study findings have
      potential implications for the provision of care, information, and support for
      patients and their families before and after transplantation and for future
      related research.

PMID- 19588661
TI  - Constantly responsible, constantly worried, constantly blessed: parenting after
      pediatric heart transplant.
AB  - CONTEXT: Very little research has focused on the long-term caregiving demands
      associated with parenting a child after a transplant or on the parents'
      perceptions of those demands. PURPOSE: To describe parents' experiences parenting
      a school-aged child after heart transplant. DESIGN: Focused ethnography.
      PARTICIPANTS AND SETTING: Eleven parents of children who had undergone heart
      transplant 2 or more years before the study were recruited from a large
      children's hospital. DATA COLLECTION AND ANALYSIS: Parents were interviewed in a
      private location of their choice. Verbatim interview transcripts were analyzed by
      using content analysis and constant comparison. RESULTS: The parents described
      their experiences in positive terms, yet acknowledged hardships. Key themes
      included (1) constantly responsible, (2) constantly worried, (3) constantly
      blessed, and (4) coping with life. The identified themes provide direction for
      interventions to help parents cope with the experience of parenting a child after
      heart transplant.

PMID- 19588662
TI  - Psychiatric disorders: are they an absolute contraindication to living donation?
AB  - Little information has been published about the suitability of candidates for
      living organ donation who have a past or current psychiatric diagnosis. A
      retrospective review of 445 living donor kidney transplants performed at Barnes
      Jewish Hospital's transplant center from 1995 to 2005 disclosed 42 donor
      candidates with such a history, prompting detailed psychological evaluation.
      Although 41 candidates (10% of the donor pool) met criteria for 1 or more
      psychiatric diagnoses, none were considered psychologically unfit for donation.
      Of these, 22 candidates underwent kidney donation without medical or surgical
      complications and without development of subsequent active psychological
      problems. Several donors maintained long-term contact up to 12 years to report
      good health and a high degree of satisfaction with the decision to donate. This
      experience suggests that for donor candidates with a psychiatric diagnosis,
      formal psychiatric evaluation to evaluate current mental health stability is
      warranted. Stable individuals, on or off therapy, can be considered fit to donate
      with expected short- and long-term outcome prognoses similar to those for the
      general population.

PMID- 19588663
TI  - Use of clinical practice guidelines to promote best practice when managing
      clinical interventions for liver transplant candidates.
AB  - BACKGROUND: Limited organ availability and an increasing demand for organ
      transplantation has extended transplant waiting times and thus increased
      morbidity and mortality for potential recipients on waiting lists. The Queensland
      Liver Transplant Service identified use of clinical practice guidelines developed
      from evidence-based practice as a strategic clinical management/workflow tool
      that could improve clinical outcomes for patients awaiting liver transplant.
      METHOD: An extensive review of publications related to the management of advanced
      liver disease in potential transplant recipients was undertaken and the
      supporting evidence was identified. In all stages of development of the
      guidelines, the multidisciplinary collaborative team of clinicians used
      recommended principles from The Appraisal of Guidelines, Research and Evaluation
      collaboration. The liver transplant recipient coordinator acted as facilitator
      for the project, identifying positive factors and resolving obstacles. RESULTS:
      Key focus areas in optimizing medical management before liver transplant were
      identified with the aim of preventing disease progression and complications that
      would jeopardize patients' outcome. Clinical practice guidelines were developed
      for each key area to optimize care by promoting appropriate timing of clinical
      interventions. CONCLUSION: Practices that required change to comply with
      identified best practice were investigated, and clinical practice for the
      outpatient medical management of potential liver transplant recipients with
      chronic liver disease were developed collaboratively. These guidelines have been
      accepted and are being implemented within the gastroenterology and hepatology
      department at the Princess Alexandra Hospital.

PMID- 19588664
TI  - Quality of life in caregivers providing care for lung transplant candidates.
AB  - CONTEXT: Caregivers are essential members of the health care team who provide
      care, valued at more than $250 billion each year, to millions of persons who
      require assistance with health and daily care. Patients with respiratory diseases
      who are waiting for a lung transplant are required to have an identified
      caregiver. The caregivers are rarely studied. OBJECTIVE: To explore the
      relationships among the health status of caregivers of lung transplant
      candidates, caregivers' reaction to caregiving, and caregivers' perceived quality
      of life. DESIGN: This descriptive study examined the quality of life of lung
      transplant caregivers from a multidimensional perspective. SETTING AND
      PARTICIPANTS: Twenty-nine dyads of lung transplant candidates and their
      caregivers were recruited from a Midwestern medical center. MEASURES: Data were
      collected by self-report: caregivers completed the Quality of Life Index, SF-12
      health survey, Profile of Mood States-Short Form, and the Caregiver Reaction
      Assessment. RESULTS: Caregivers reported favorable levels of quality of life,
      physical health, and mood during the pretransplant waiting phase. However,
      problem areas for caregivers during this time included fatigue, depression, and
      the financial impact of the transplant. Data analyses indicated that depression,
      caregiver general health, impact on finances, and lack of family support had the
      greatest effect on caregivers' quality of life. Nurses are urged to recognize the
      role of caregivers in the transplant process, ask about and listen to caregivers'
      needs, and include caregivers in the plan of care.

PMID- 19588665
TI  - Effect of annual influenza immunization on antibody response in lung transplant
      patients.
AB  - BACKGROUND: Influenza viral infections cause significant morbidity and mortality
      each season. Lung transplant patients may be at higher risk because of their
      underlying pathophysiology. Although annual immunization is the standard of care,
      its efficacy remains largely unproven. Previous studies showed poor antibody
      response to influenza vaccine in lung transplant patients, but no data on the
      antibody response in consecutive seasons have been published. METHODS: We studied
      antibody responses to influenza vaccine in 122 subjects: 66 lung transplant
      recipients, 28 control subjects, and 28 patients awaiting lung transplantation.
      We compared antibody response rates to individual viruses contained in influenza
      vaccines in consecutive years within the 3 groups. Serum antibody concentrations
      were measured at baseline and 2 to 4 weeks after vaccination by using the
      hemagglutination inhibition assay. Log-transformed antibody concentrations and
      incidence of serconversion and seroprotection were calculated. RESULTS: Median
      log-transformed antibody responses were similar in consecutive seasons in lung
      transplant subjects. Incidences of seroprotection and seroconversion did not
      differ between consecutive seasons in lung transplant recipients. CONCLUSIONS:
      Antibody responses were similar in consecutively measured years in lung
      transplant subjects. Annual influenza vaccination in lung transplant subjects
      produces similar immune responses in 2 consecutive years, indicating that these
      patients are not at significantly increased risk of vaccine failure.

PMID- 19588666
TI  - Developing new ways to address learning needs of adult abdominal organ transplant
      recipients.
AB  - CONTEXT: The degree to which patients are knowledgeable about posttransplant care
      can affect outcomes and patients' satisfaction. Transplant team members must
      identify knowledge gaps, contributory factors, and innovative methods to address
      learning needs. OBJECTIVE: To identify patients' perceptions of their knowledge
      gaps and identify ways to improve current approaches to patient education.
      DESIGN: Nonexperimental. SETTING: Midwestern teaching hospital. PATIENTS: 726
      adult abdominal organ transplant recipients. INTERVENTION(S): A patient education
      survey was mailed out to solid-organ transplant recipients who met study
      criteria. A modified version of the Patient Learning Needs Scale (PLNS) was used
      to identify the recipients' learning needs. Additional questions on the survey
      addressed factors that we hypothesized would influence responses to the PLNS and
      asked patients which methods would help them learn during various phases of the
      transplant process. MAIN OUTCOME MEASURE(S): Statistical analysis was conducted
      on survey responses. RESULTS: Overall, PLNS scores were satisfactory in all 4
      categories. Analysis of PLNS subscales revealed significantly lower scores in the
      quality of life/psychosocial subscale compared with the other 3 subscales.
      Significantly lower scores in the medications and follow-up categories of the
      PLNS items were found among the group whose length of stay was between 15 to 30
      days compared with patients with shorter and longer stays. A variety of different
      methods are desired by patients in order to get information, especially before
      transplant.

PMID- 19588667
TI  - Medication adherence in successful kidney transplant recipients.
AB  - OBJECTIVE: To explore the medication-taking behavior of successful kidney
      transplant recipients and determine what behaviors were common among this group.
      METHODS: Open-ended interviews were conducted by telephone with 19 individuals
      who had successfully maintained a transplanted kidney for 25 years or more. Data
      were coded by using a grounded theory approach to explore patterns of phenomena,
      common descriptions, and relationships. RESULTS: Four themes emerged as
      participants described the behaviors they developed to adhere successfully to the
      immunosuppressive medication required for maintaining their transplanted kidneys.
      The themes were reminder methods, obtaining medications, maintaining routines,
      and problem-solving strategies. Kidney transplant recipients identified the
      importance of developing and maintaining medication-taking skills and routines on
      medication adherence. Problem-solving abilities were also valuable during times
      of disruption of normal routines. CONCLUSIONS: Interventions focusing on
      medication-taking skills, habit formation, and resources for problem solving may
      improve immunosuppressive medication adherence and clinical outcomes in kidney
      transplant recipients.

PMID- 19588668
TI  - Relationship of exposure to organ donation information to attitudes, beliefs, and
      donation decisions of next of kin.
AB  - CONTEXT: Public education campaigns about organ donation are common, but their
      association to actual attitudes, beliefs, and decisions about organ donation
      among family members of donation-eligible individuals is unknown. OBJECTIVE: To
      examine the sources of organ donation information identified by donor and
      nondonor families who participated in a large-scale study to examine factors that
      influence organ donation decisions. DESIGN: Semistructured telephone survey
      conducted after a passive recruitment strategy. SETTING AND PARTICIPANTS:
      Participants were 285 next of kin of donor-eligible individuals (147 donors, 138
      nondonors) from one organ procurement organization. RESULTS: Most (85.6%) of next
      of kin were exposed to at least 1 source of donation information that was
      important to them, although the types of donation information they were exposed
      to varied widely. White and educated adults were more likely to have been exposed
      to more donation information than had minorities and persons with less education.
      Favorable attitudes and beliefs about organ donation, donor designation, and
      sharing donation intentions with others were all associated with more exposure to
      different types of donation information. Donation consent was more likely when
      next of kin had been exposed to more donation information in the months preceding
      the family member's death. CONCLUSIONS: When examined in the context of other
      recent research, these findings argue for continued development and
      implementation of public education campaigns for organ donation, with an emphasis
      on repeated exposure over time.

PMID- 19588669
TI  - Improving donation outcomes: hospital development and the Rapid Assessment of
      Hospital Procurement Barriers in Donation.
AB  - CONTEXT: Deficiencies in the donation process continue to contribute to the
      shortage of organs available for transplant. Continuous quality improvement of
      hospitals' donation processes is needed to identify and correct the problems.
      OBJECTIVE: To test the Rapid Assessment of Hospital Procurement Barriers in
      Donation (RAPiD), a direct observation technique with a focused ethnographic
      strategy, for assessing hospitals' donation processes and identifying areas in
      need of continuous quality improvement interventions. DESIGN: A pre-post
      assessment of hospitals' barriers to patient identification and referral, and
      family consent to donation. SETTING AND PARTICIPANTS: Seventeen hospitals within
      the catchment area of a Northeastern organ procurement organization were assessed
      by using the RAPiD method. Hospital administrators, health care providers, and
      staff (N = 537) were interviewed as part of the assessments. INTERVENTION:
      Interventions, including on-site training and education, and the use of in-house
      coordinators, were specifically tailored to each hospital's unique set of
      barriers to donation. The interventions were delivered to the hospitals in the
      form of recommendations. The participating organ procurement organization was
      responsible for implementation of the interventions. RESULTS: The RAPiD hospital
      evaluations revealed gaps in respondents' knowledge of organ donation, brain
      death, and referral criteria; a reluctance to declare brain death; and a rocky
      relationship between the hospitals and the organ procurement organization. As a
      result of the interventions, 9 hospitals' environments for organ donation
      improved, 7 showed no change, and 1 was worse.

PMID- 19588670
TI  - Exploring transplant opportunities in Hmong culture: a case report.
AB  - A clinical case is used to explore the ethical complexities of solid organ
      donation and transplantation within the Hmong community in the United States.
      Although many cultures can present various ethical issues, the challenges of the
      Hmong belief system are unique and distinctly complex. Ways for the medical team
      to integrate with the Hmong value system to attempt to create an environment of
      transcultural respect and appreciation are described.

PMID- 19588671
TI  - Skin diseases.

PMID- 19588672
TI  - A 12-year-old girl with abdominal pain and vomiting.

PMID- 19588673
TI  - An 11-month-old girl with high fever. Kawasaki disease.

PMID- 19588674
TI  - Use of isotretinoin for acne vulgaris.

PMID- 19588675
TI  - Molluscum contagiosum: what's new and true?

PMID- 19588676
TI  - Pediatric infestations.

PMID- 19588677
TI  - Therapies for pediatric seborrheic dermatitis.

PMID- 19588678
TI  - Vitiligo: treatment approach in children.

PMID- 19588679
TI  - 400 years after Galileo Galilei.

PMID- 19588680
TI  - Prognostic factors in haemotoxic viper bite: analysis of data from a referral
      hospital.
AB  - To identify the predictors of severe outcomes in patients with haemotoxic viper
      bite certain independent variables were recorded like age, sex, ethnicity, bite
      sites, duration of prehospital period, prehospital treatment, onset of systemic
      bleeding, local oedema, ecchymoses, blister, hematocrit, platelet count, whole
      blood clotting time, serum electrolytes, renal function and urinary examination
      findings in 62 hoptalised patients. Forward stepwise logistic regression was used
      for analysis of the independent factors predicting outcomes. Systemic bleeding
      was the commonest complication (45%). On multivariate analysis, alteration in
      coagulation parameters (like thrombocytopenia and prolonged whole blood clotting
      time) predisposed to systemic bleeding while local factors like bite site, faulty
      tourniquet application, and herbal treatment were responsible for local
      complications. Factors like massive envenomation and delayed hospitalisation
      significantly contributed to major organ damage. Predictors of death were anuria
      and systemic bleeding. It is concluded that several epidemiological, clinical,
      and laboratory features predict adverse outcomes in haemotoxic viper bite.

PMID- 19588681
TI  - Persons with major psychiatric illness in prisons--a three years study.
AB  - A research project entitled 'operation oasis' was implemented in West Bengal
      prisons by SEVAC, supported by the National Human Rights Commission of India for
      identification of the persons suffering from major psychiatric illnesses (ie,
      schizophrenia, psychosis not otherwise specified, mood disorder not otherwise
      specified) in prisons, making arrangements for their psychiatric treatment and
      rehabilitation and assessing the changes in them after intervention. Dum Dum
      Central Jail, Presidency Jail (female section), and Berhampore Central Jail were
      selected as the project fields. The prison inmates were screened through clinical
      examination and mental state examination. Among them who were found suffering
      from mental illness were brought under psychiatric and psychological treatment,
      rehabilitation and restoration. Their sociodemographical data were also collected
      on the basis of a structured information schedule developed by the SEVAC team.
      The patients were followed-up for three consecutive years (2001 to 2004). The
      global assessment of functioning scores of the patients recorded at the time of
      initiation and completion of project were compared. During the project
      implementation period, 3871 prison inmates (male 3527 + female 344) were screened
      and 10% (n = 401) were identified as suffering from major psychiatric illnesses,
      of which 64% (n = 258) were housed in the prisons for minor offences/stray cases
      and 90% (n = 363) were undertrials. The findings concluded with a global
      assessment of functioning score improvement with a statistical significance of p
      < 0.01 level (Z = 5.06) for the patients. This study shows that a qualitative
      change took place in the life situations of the mentally ill people who were
      brought under the purview of psychiatric treatment and rehabilitation.

PMID- 19588682
TI  - Clinicohaematological analysis of aplastic anaemia among children of northern
      districts of West Bengal.
AB  - Though aplastic anaemia in children is an important haematological disorder, not
      many studies have been undertaken in India and especially in the northern
      districts of West Bengal. The present study was carried out at North Bengal
      Medical College and Hospital to find the occurrence, clinical and hematological
      profile of children with aplastic anaemia. All the children (less than 15 years)
      having relevant history and clinical features underwent a complete blood count
      and bone marrow aspiration study (smear and histological sections) and trephine
      biopsy. Total number of children diagnosed were 21 (M = 17, F = 4), having an age
      range of 6-14.5 years (mean 11.36). Relevant aetiological factors were noted in
      10 cases (47.61%), including history of exposure to insecticides, fungicides and
      fertilisers in 5 cases (23.81%). The common symptoms were due to anaemia
      (weakness, pallor in all cases), leucopoenia [fever in 16 cases (76.19%)] and
      thrombocytopenia [bleeding in 10 cases (47.61%)]. Severe and moderate aplastic
      anaemia were noted in 7 (33.33%) and 12 (57.14%) cases respectively. The
      calculated occurrence of aplastic anaemia is 1.96/million population of
      children/year in the four northern districts of West Bengal. The bone marrow
      aspiration was satisfactory in all cases. Histological sections of aspirated
      marrow particle produced better architectural relationship among different
      components. Aplastic anaemia is a major hematological problem among the children
      of northern districts of West Bengal. Simultaneous examination of smear and
      histological sections of marrow particles is a satisfactory method for detection
      of aplastic anaemia.

PMID- 19588683
TI  - Bacterial incidence and antibiotic sensitivity pattern in moderate and severe
      infections in hospitalised patients.
AB  - Infectious diseases are among the leading causes of death and sometimes curable.
      Bacteria are the most common aetiology in hospitalised patients. Objectives of
      this study were to evaluate the incidence of bacterial infections and their
      pattern of susceptibility to antibiotics in moderate and severe infections in
      hospitalised patients. The study was performed in the apical teaching hospital of
      West Bengal in the first half of 2005. Patients admitted in medical wards and
      medical ICU, suffering from moderate and severe infections having APACHE-II score
      > 5 were studied. Clinical evaluation, routine and specific investigations were
      done in each case. Microbiological samplings were tried on day 1, after
      completion of antibiotic therapy and in between as required. Aerobic BACTEC
      bacterial culture and sensitivity tests were done. Pending initial culture and
      sensitivity report empiric antibiotic therapy was started, which was modified on
      getting the culture and sensitivity report. Outcome was observed as no response,
      cured, resolved, inconclusive, died and left against medical advice. Out of 40
      patients total number of samples were 54 and that of sites of infections were 48.
      Primary site could not be detected in 11 infections (22.9%). Commonest form was
      urinary tract infection and abdominal infection in community acquired infection
      (n=18) and pneumonia in hospital acquired infection (n = 15). Culture was
      positive in 33 (61.11%), Gram-negative infection was more common in general, but
      incidence of Gram-positive infection was also quite high and Gram-positive
      infection was more common in community acquired infection. In general S aureus
      was most common bacteria -8 (24.24%). In community acquired infection S aureus 4
      (22.22%) predominated followed by E coli and in hospital acquired infection S
      aureus -4 (26.66%) followed by E coli and P aeruginosa. Incidence of methicillin
      resistant Staph aureus was low. But it constituted 50% of S aureus. No
      methicillin resistant Staph aureus was found in community acquired infection. Two
      isolates of vancomycin intermediate sensitive Staph aureus were observed.
      Methicillin resistant Staph aureus showed maximum sensitivity to linezolid (100%)
      and all methicillin resistant Staph aureus but one vancomycin intermediate
      sensitive Staph aureus were sensitive to vancomycin. Coagulase negative Staph
      aureus were all sensitive to vancomycin and linezolid. Gram-negatives were mostly
      resistant to aminoglycosides and P aeruginosa were all sensitive to aztreonam.
      Single strain of S typhi as isolated was resistant to ceftriaxone and
      ciprofloxacin. P miribalis, P aeruginosa and coagulase negative Staph aureus were
      notoriously multidrug resistant; 82.5% of cases responded to treatment of which
      35% were cured microbiologically. Gram-negative infection was more common
      overall, but incidence of Gram-positive infection was also very high. Gram
      negative infections were responsible for more severe infections and case
      fatality. Multidrug resistant Gram-positive infections are rising.

PMID- 19588684
TI  - Comparative study of postoperative analgesia and sedation after upper abdominal
      surgery with thoracic epidural administration of bupivacaine with/without
      midazolam.
AB  - Currently continuous epidural administration of local anaesthetics with opioids
      is widely used for postoperative analgesia. To avoid the side-effects of opioids
      a drug that can replace opioids is most welcome. Midazolam not only has no side
      effects but also has the advantages of sedation and amnesia. In a prospective
      randomised clinical study ASA class 1 or 2 patients undergoing upper abdominal
      surgeries were studied to compare the analgesic and sedative effect of continuous
      thoracic epidural infusion of bupivacaine versus continuous thoracic epidural
      administration of bupivacaine with midazolam postoperatively. They were divided
      into 2 groups. Via thoracic epidural route patients in group A (n = 24) were
      given 60 ml of 0.25% bupivacaine while those in group B (n = 25) were given 58 ml
      of 0.25% bupivacaine + midazolam 2 ml (10 mg). Each patient was infused using a
      syringe pump at the rate of 5 ml/hour. Variables studied postoperatively were
      pulse, BP, RR, SpO2, analgesia score and sedation score. Statistically
      significant differences in pulse, BP, RR and SpO2 were not seen. Better sedation,
      analgesia scores and amnesia were noted in patients belonging to group B as
      compared to patients of group A. This combination may thus replace routinely used
      combinations of opioids and local anaesthetics.

PMID- 19588686
TI  - Teenage pregnancy: a comparative study of the outcome and complications.
AB  - This study compares the outcome and complications of pregnancy among teenagers
      with those above 19 years of age. This retrospective study conducted in a
      maternity hospital in rural Karnataka, under the guidance of the department of
      community medicine, St Johns National Academy of Health Sciences, Bangalore,
      included 221 women who delivered between February 2003 and April 2003. The data
      was tabulated in excel spreadsheet and analysed using epi 6 programme. Anaemia
      among teenage multigravidae was found to be a significant health problem. There
      were no statistically significant differences between the gestational age at
      delivery and the mode of delivery in the different age groups. Teenage pregnancy
      was not found to be associated with an increased risk for antenatal complications
      or postnatal complications. There was no increased incidence of low birth weight
      or congenital anomalies among the babies of teenage mothers. Mortality was not
      found to be increased both among the teenage mothers as well as their babies.

PMID- 19588685
TI  - A prospective evaluation of anterior chamber contamination following cataract
      surgery.
AB  - Anterior chamber aspirate cultures were done in 57 patients who underwent
      uncomplicated manual small incision cataract surgery with posterior chamber intra
      ocular lens implantation. The aspirates were collected at the time of wound
      closures. The specimens were immediately inoculated into blood agar, chocolate
      agar and thioglycolate broth. The cultures were incubated at 37 degrees C with 5%
      CO2 and held for 5 days. Out of 57 patients 8 (14%) had culture positive anterior
      chamber aspirates. Coagulase negative staphylococcus was the commonest (62%). No
      anaerobic organism was detected. None of the eyes developed endophthalmitis. The
      study concluded that the strict aseptic measures, the antimicrobial property of
      the aqueous humour or small inoculum size could be the possible factors to
      prevent fulminating infection.

PMID- 19588687
TI  - Antenatal diagnosis of Down syndrome: how good is state of the art.
AB  - A newborn with Down syndrome can be expected once in a thousand deliveries.
      Amniocentesis for karyotyping of foetal cells or detection of foetal cell in the
      maternal circulation ie, fluorescent in-situ hybridisation (FISH) and
      karyotyping, are definitive methods of making the diagnosis antenatally. The cost
      of doing this routinely in all pregnancies is prohibitive. This has led to
      dependence on screening tests, to select women more likely to be carrying a Down
      foetus, to offer karyotyping in a more cost efficient manner. Unfortunately,
      these screening criteria, namely maternal age, biochemical markers and ultrasound
      pointers, are rather insensitive and miss a large number of cases of Down
      syndrome. At the same time they are very non-specific, picking up a large number
      of false positive cases, resulting in undue anxiety and unnecessary alarm in a
      large number of mothers. Till a non-invasive, definitive test, like FISH can be
      routinely used in all pregnancies at affordable costs, accurate antenatal
      diagnosis on a community basis will be a hit and miss affair.

PMID- 19588688
TI  - Chirality and drugs in clinical practice and its ethical aspect.
AB  - Recently specific enantiomer of different chiral molecules are being launched in
      the market as drugs. Here the rationality of scopes and uses of these drugs in
      therapeutic medicine is discussed including the ethical aspect.

PMID- 19588689
TI  - Sirenomelia: a case report.
AB  - Sirenomelia (Mermaid syndrome) is a rare anomaly of caudal region of the body,
      presented with fusion of the lower limbs. Genito-urinary, gastro-intestinal,
      neural tube and vertebral anomalies are found in most cases. Here a case of
      sirenomelia born of a 5th gravida mother is reported. The body had fusion of both
      lower limbs, absent genitalia, absent anal orifice and single umbilical artery.
      It died 2 1/2 hours after birth. Autopsy was undertaken to verify various
      anomalies.

PMID- 19588690
TI  - Non-renal Wegener's granulomatosis in a young housewife.

PMID- 19588691
TI  - Synchronous double pathology of lung: a diagnostic dilemma.

PMID- 19588692
TI  - The current economy--challenges and opportunities.

PMID- 19588693
TI  - Integrating a culture of caring into a technologic world.

PMID- 19588694
TI  - Stressors and coping in individuals with chronic kidney disease.
AB  - The purpose of this study was to develop a valid and reliable instrument to
      measure stressors of patients with chronic kidney disease (CKD), identify those
      stressors, and determine which coping strategies were used and effective. The
      participants reported fatigue, sleep problems, and peripheral neuropathy as the
      most frequently experienced stressors. Optimism as a coping style was most
      commonly used and was also the most effective. Stress was inversely associated
      with age and CKD stage, and positively associated with coping. Knowledge from
      this study can be used to further patient education and supportive interventions
      for patients with CKD.

PMID- 19588695
TI  - Patient questions about transplantation: a resource guide.
AB  - Patients with chronic kidney disease who are on dialysis may ask questions
      related to kidney transplantation. Comprehensive patient education prior to
      transplantation empowers patients with knowledge about all aspects of care that
      are crucial to the success of the transplant. Patients who receive extensive
      education about medications, monitoring, and responsibilities related to kidney
      transplantation are more likely to succeed with self-management after
      transplantation. Nurses and other staff in dialysis units do not always have the
      resources to answer questions about transplantation. This article is designed to
      serve as a resource guide to assist them in answering patient questions related
      to transplant evaluation, transplant medications, complications of
      transplantation, and the responsibilities of the kidney transplant recipient.

PMID- 19588696
TI  - Dialysis staff encouragement and fluid control adherence in patients on
      hemodialysis.
AB  - BACKGROUND: Fluid control in patients on dialysis is an important predictor of
      outcome but is a difficult restriction to achieve. The authors examined the
      association between dialysis staff encouragement and fluid control adherence in
      patients on hemodialysis. METHODS: This cross-sectional study used the dialysis
      staff encouragement subscale (DSE). The outcome measure was intradialytic weight
      loss (IWL) of dry weight (DW), with nonadherence defined as IWL/DW greater than
      5.7%. Predictors of nonadherence were identified using logistic regression. Odds
      ratio (OR) was for the occurrence of nonadherence as it correlated with a one
      standard deviation (SD) decrease in scale score. RESULTS: Seventy-two patients on
      hemodialysis participated, 45 men (62.5%) and 27 women. The crude OR in DSE score
      was 1.75 (95% confidence interval [CI]: 1.02 to 3.0) and adjusted odds ratio was
      2.51 (95% CI: 0.99 to 6.34). CONCLUSION: Dialysis staff encouragement is
      important in improving fluid control adherence.

PMID- 19588698
TI  - Using 'Tandem hand' technique to facilitate self-cannulation in hemodialysis.
AB  - Self-cannulation has been shown to decrease complications and extend the life of
      the arteriovenous fistula. Teaching self-cannulation has been difficult due to
      patient distress created by the use of needles. This article discusses a
      technique that has been used in the authors' clinic to teach self-cannulation to
      incenter patients. The observed use of this technique has helped create a
      comfortable environment for the patient.

PMID- 19588697
TI  - Modifiable practice patterns and patient outcomes: implications for nephrology
      nursing care.
AB  - Data indicate that patient outcomes are significantly affected by factors that
      can be modified through clinical practices, such as vascular access choice,
      dialysis dose, interdialytic weight gain, albumin and hemoglobin levels, and
      mineral and bone disorders. This article reviews recommended treatment guidelines
      for these factors and the ways patient outcomes are affected when targets are not
      achieved. Insights on how nursing practices can positively affect these
      components of care are also provided.

PMID- 19588699
TI  - CKD education: an evolving concept.

PMID- 19588700
TI  - Is heparin required to prevent thrombosis of an indwelling catheter?

PMID- 19588701
TI  - Oral health care for patients on dialysis.
AB  - The incidence of many dental conditions seems to be high in patients on dialysis,
      and nephrology nurses should be vigilant to their dental status. If dental
      concerns are not addressed properly in a timely manner, they can cause infections
      that can lead to more health issues. Proper oral hygiene (brushing, flossing, and
      regular dental examinations) can help prevent dental concerns from leading to
      more serious health problems, such as sepsis.

PMID- 19588702
TI  - Is music therapy?
AB  - Music therapy as a method of intervention may enhance the quality of life of
      patients on dialysis by reducing anxiety, depression, and other psychosocial
      responses as a result of hemodialysis. This article presents a study that
      experimented with music therapy during dialysis sessions in order to improve the
      treatments and allow patients the opportunity to participate in their healthcare
      program.

PMID- 19588703
TI  - The timeless message of silence.

PMID- 19588704
TI  - Pharmacotherapy of hepatitis C virus infection: a brief review.
AB  - Infection with the hepatitis C virus is a major public health problem and is the
      leading cause of liver disease in the United States. Chronic infection with
      hepatitis C virus can lead to liver disease, cirrhosis, and hepatocellular
      carcinoma. Treatment options include interferon or peginterferon, and ribavirin.
      The objective of treatment is to eradicate the infection in an effort to prevent
      complications of hepatitis C virus infection.

PMID- 19588705
TI  - 2009: the year of nurse wellness.

PMID- 19588706
TI  - Lessons learned in diligence from H1N1.

PMID- 19588707
TI  - Standing at the crossroads.

PMID- 19588708
TI  - The financial challenges of obtaining quality substance abuse treatment.

PMID- 19588710
TI  - Call to regulate nanotechnology.

PMID- 19588711
TI  - Not 'just' a nurse.

PMID- 19588712
TI  - Striving for equity.

PMID- 19588713
TI  - Who cares for the elderly? Aged care nurses do.

PMID- 19588714
TI  - Spotlight on Super.

PMID- 19588715
TI  - The management of chronic wounds.
AB  - The burden that chronic wounds create for both the client and healthcare provider
      is set to increase. For clinicians managing wounds it is essential that slow to
      heal wounds are identified early and treated promptly. The early removal of
      necrotic tissue, adequate control of exudate and the reduction of any bioburden
      are key foundations for any management plan.

PMID- 19588716
TI  - Joint guideline on influenza pandemic.

PMID- 19588717
TI  - Registered nurse and serial killer.

PMID- 19588718
TI  - Celebrating 60 years at Peter Mac.

PMID- 19588719
TI  - Good oral hygiene practice.

PMID- 19588720
TI  - Bone marrow transplantation at the RHH.

PMID- 19588721
TI  - Aseptic non-touch technique.

PMID- 19588722
TI  - A very public death. Mesothelioma & asbestos-related lung cancer.

PMID- 19588723
TI  - Aromatherapy in nursing practice.

PMID- 19588724
TI  - International virtual research seminar on cancer research. Interview by Judith
      Kingston.

PMID- 19588726
TI  - High fat diet-induced obesity modifies the methylation pattern of leptin promoter
      in rats.
AB  - Leptin is an adipokine involved in body weight and food intake regulation whose
      promoter region presents CpG islands that could be subject to dynamic
      methylation. This methylation process could be affected by environmental (e.g.
      diet) or endogenous (e.g., adipocyte differentiation, inflammation, hypoxia)
      factors, and could influence adipocyte leptin gene expression. The aim of this
      article was to study whether a high-energy diet may affect leptin gene promoter
      methylation in rats. A group of eleven male Wistar rats were assigned into two
      dietary groups, one fed on a control diet for 11 weeks and the other on a high
      fat cafeteria diet. Rats fed a high-energy diet become overweight and
      hyperleptinemic as compared to the controls. DNA isolated from retroperitoneal
      adipocytes was treated with bisulfite and a distal portion of leptin promoter
      (from -694 to -372 bp) including 13 CpG sites was amplified by PCR and sequenced.
      The studied promoter portion was slightly more methylated in the cafeteria-fed
      animals, which was statistically significant (p < 0.05) for one of the CpG sites
      (located at the position -443). In obese rats, such methylation was associated to
      lower circulating leptin levels, suggesting that this position could be important
      in the regulation of leptin gene expression, probably by being a target sequence
      of different transcription factors. Our findings reveal, for the first time, that
      leptin methylation pattern can be influenced by diet-induced obesity, and suggest
      that epigenetic mechanisms could be involved in obesity by regulating the
      expression of important epiobesigenic genes.

PMID- 19588727
TI  - Influence of prolonged fasting on monoamine oxidase and semicarbazide-sensitive
      amine oxidase activities in rat white adipose tissue.
AB  - Monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO)
      activities are very high in white adipose tissue (WAT). SSAO, also known as
      Vascular Adhesion Protein-1 in vessels, is present at the surface of fat cells
      and independent approaches have evidenced its impressive increase during
      adipogenesis. However, the factors that might regulate the expression SSAO and
      MAO in adipose tissue are still poorly defined. Here, we report the influence of
      fasting on MAO and SSAO activities in adipose depots. A decrease of MAO activity
      occurred after three days of starvation in the intra-abdominal adipose tissue
      (INWAT) of male Wistar rats, regardless of their initial adiposity or fat loss.
      The reduced fat stores of seven-week old rats, loosing 59 % of INWAT mass during
      fasting, contained only one half of the MAO activity found in fed control. The
      same reduction of MAO was observed after prolonged fasting in older rats which
      lose only 26% of their INWAT during the same starvation duration, leading to a
      fat mass comparable to that of younger fed control rats. It was therefore the
      endocrine and metabolic changes occurring during fasting that were responsible
      for the reduced MAO activity and not the amount of INWAT. Surprisingly, SSAO
      activity remained unchanged during starvation. In subcutaneous WAT, the changes
      in MAO and SSAO activities exhibited the same tendencies than those found in
      INWAT. Taken together, these data show that both MAO and SSAO activities increase
      in INWAT with age-dependent fattening, and indicate that only MAO diminishes
      during fasting.

PMID- 19588728
TI  - A comparison between CLNA and CLA effects on body fat, serum parameters and liver
      composition.
AB  - The potential of conjugated linoleic acid (CLA) as an anti-obesity molecule for
      humans is still a matter for debate. Thus, a great deal of scientific work is
      focussed on the research of new effective molecules without deleterious effects
      on health. The aim of the present work was to analyse the effects of jacaranda
      seed oil, rich in a conjugated linolenic acid (CLNA), jacaric acid (cis-8,trans
      10,cis-12), on body fat, serum parameters and liver composition in rats, and to
      compare these effects with those of trans-10,cis-12 CLA. Twenty-six male Wistar
      rats were divided into three groups fed with high-fat diets, supplemented or not
      (control group) with 0.5% trans-10,cis-12 CLA (CLA group) or 0.5% jacaric acid
      (CLNA group) for 7 weeks. No statistical differences in food intake or in final
      body weight were found. Whereas CLA reduced adipose tissue size, CLNA did not.
      Both CLA and CLNA significantly reduced non-HDL-cholesterol. In spite of a lack
      of significant changes in glucose and insulin levels, HOMA-IR index was
      significantly increased, as well as did non-esterified fatty acid levels in CLNA
      fed rats. No changes in liver composition were observed. In conclusion, under our
      experimental conditions, jacaric acid, unlike CLA, does not show a body-fat
      lowering effect. Even though it leads to a healthy lipoprotein profile, it
      impairs insulin function. Consequently, it cannot be proposed as an anti-obesity
      molecule.

PMID- 19588729
TI  - High lipolytic activity and dyslipidemia in a spontaneous hypertensive/NIH
      corpulent (SHR/N-cp) rat: a genetic model of obesity and type 2 diabetes
      mellitus.
AB  - In order to better understand the link between obesity and type 2 diabetes,
      lipolysis and its adrenergic regulation was investigated in various adipose
      depots of obese adult females SHR/N-cp rats. Serum insulin, glucose, free fatty
      acids (FFA), triglycerides (TG) and glycerol were measured. Adipocytes were
      isolated from subcutaneous (SC), parametrial (PM) and retroperitoneal (RP) fat
      pads. Total cell number and size, basal lipolysis or stimulated by norepinephrine
      (NE) and BRL 37344 were measured in each depot. Obese rats were hyperinsulinemic
      and hyperglycemic, suggesting high insulin resistance. They presented a marked
      dyslipidemia, attested by increased serum FFA and TG levels. High serum glycerol
      levels also suggest a strong lipolytic rate. Obese rats showed an excessive
      development of all fat pads although a more pronounced effect was observed in the
      SC one. The cellularity of this depot was increased 8 fold when compared to lean
      rats, but these fat cells were only 1.5 to 2-fold larger. SC adipocytes showed a
      marked increase in their basal lipolytic activity but a lack of change in
      responsiveness to NE or BRL 37344. The association between high basal lipolysis
      and increased cellularity yields to a marked adipose cell lipolytic rate,
      especially from the SC region. SHR/N-cp rats were characterized by a hyperplasic
      type of obesity with an excessive development of the SC depot. The dyslipidemia,
      attested by an altered serum lipid profile could be attributed to excessive
      lipolysis that contributes to increased FFA levels, and to early development of
      insulin resistance through a lipotoxicity effect.

PMID- 19588730
TI  - Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects
      on intestinal sugar transport.
AB  - Several studies have suggested that oxidative stress might cause and aggravate
      the inflammatory state associated with obesity and could be the link between
      excessive weight gain and its related disorders such as insulin resistance and
      cardiovascular diseases. Thus, antioxidant treatment has been proposed as a
      therapy to prevent and manage obesity and associated complications. Therefore,
      the aim of the present study was to investigate the effects of supplementation of
      a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days,
      on body weight gain, adiposity, feed efficiency and intestinal sugar absorption,
      in male Wistar rats. LA supplementation induced a lower body weight gain and
      adipose tissue size in both control or high fat fed rats accompanied by a
      reduction in food intake. The group fed on a high fat diet and treated with LA
      (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF)
      group (P < 0.05), which received the same amount of food than LA-treated animals
      but with no LA. In fact, LA induced a reduction on feed efficiency and also
      significantly decreased intestinal alpha-methylglucoside (alpha-MG) absorption
      both in lean and obese rats. These results suggest that the beneficial effects of
      dietary supplementation with LA on body weight gain are mediated, at least in
      part, by the reduction observed in food intake and feed efficiency. Furthemore,
      the inhibitory action of LA on intestinal sugar transport could explain in part
      the lower feed efficiency observed in LA-treated animals and therefore,
      highlighting the beneficial effects of LA on obesity.

PMID- 19588731
TI  - Serum transaminases concentrations in obese children and adolescents.
AB  - The aim of the study was to investigate the relationship between liver
      transaminase levels and metabolic syndrome (MS) features in obese children and
      adolescents. A total of 132 children and adolescents (73 males and 59 females)
      aged 8 - 16, participated in the study. All were studied at the department of
      Paediatrics, University Hospital of Zaragoza (Spain). Inclusion criteria were the
      existence of obesity as defined by body mass index (BMI) according to Cole cut
      off values (when BMI was higher than the age and sex specific equivalent to 30
      kg/m2). The definition of metabolic syndrome was according to the International
      Diabetes Federation criteria. Weight (kg), height (cm), waist circumference (cm),
      blood pressure and BMI were measured. Laboratory determinations after overnight
      fasting included: transaminases (ALT, AST, GGT), fasting glucose, insulin,
      triglycerides and HDL-C. The MS was found in 21.6% of the obese children and
      adolescents and the prevalence was higher in males (25.9%) than in females
      (15.9%). Serum transaminases (ALT, AST and GGT) mean concentrations were higher
      in males than in females, and decreased during pubertal development. The obese
      children and adolescents with the MS did not show higher transaminases
      concentrations when compared with those without the MS. Some MS manifestations
      (mainly waist circumference) showed a correlation with ALT, although all
      transaminases values were normal according to adult references. Liver
      transaminases, a surrogate marker of NAFLD, did not show an early and consistent
      manifestation of abnormalities in the obese children and adolescents studied. In
      order to define the presence of the disease, it would be necessary to obtain
      aminotransferase reference standards for children and adolescents, considering
      pubertal stage and gender.

PMID- 19588732
TI  - Hematological, immunological and neurochemical effects of chronic amphetamine
      treatment in male rats.
AB  - In the present study, we have analyzed the effect of chronic amphetamine sulfate
      (AMPH) treatment on haematological, immunological and neurochemical parameters in
      the male rat. AMPH increased the total peripheral leukocyte count, and altered
      its differential counts, decreasing lymphocytes and increasing neutrophils. Flow
      cytometry study showed that the decline in circulating lymphocytes was caused by
      the loss of a particular lymphocyte subset, B-cell, which reduced both in
      percentage and in absolute number by 50%. T-cell population increased by 15% but
      not in absolute number, however there was no difference in either CD4+ or CD8+ T
      lymphocyte subsets between experimental groups. Neurochemically, AMPH reduced
      norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus and
      increased dopamine (DA) content in the striatum. Chronic AMPH increased in a dose
      dependent manner serum corticosterone levels, had no effect on circulating
      catecholamines, reduced adrenal weights, and did not affect spleen weights
      although reduced their cellularities. These results show that chronic AMPH have
      important effects on immune function, particularly on humoral immune response
      because it reduced the circulating B cell population by half. In addition, AMPH
      plays an important role in the redistribution and trafficking of leukocytes, and
      both effects seem to be mediated by sympathetic innervation of the lymphoid
      organs.

PMID- 19588733
TI  - LPS differentially affects vasoconstrictor responses: a potential role for RGS16?
AB  - The profound hypotension in septic shock patients is difficult to treat as it is
      accompanied by depressed constrictor responses to alpha1-adrenoceptor agonists.
      Bacterial lipopolysaccharide (LPS) is the main trigger for most of the
      cardiovascular alterations occurring in septic shock. In this study we
      investigated the effects of LPS exposure on vascular contractility in general and
      the role of Regulator of G protein Signalling (RGS) proteins in the LPS-induced
      vascular alterations. Exposure of rat aortic rings to various LPS concentrations
      (3, 10, 30 microg/ml) for 22 hours differentially affected agonist-induced
      contractile responses at four distinct G-protein coupled receptors (alpha1
      adrenoceptors, angiotensin II, serotonin and endothelin-1 receptors). While the
      endothelin-1-induced contraction was unaffected by LPS pre-treatment,
      phenylephrine- and angiotensin II-induced contraction were significantly reduced
      whereas serotonin-induced contraction was significantly enhanced. Concomitantly,
      LPS treatment increased the RGS16 mRNA expression both in aortic rings and
      cultured vascular smooth muscle cells (VSMCs) but not that of RGS2, RGS3, RGS4 or
      RGS5. The significant increase in RGS16 mRNA expression in VSMCs by LPS was time-
      and concentration-dependent but independent of increased inducible NO synthase
      (iNOS) activity. The changes in RGS16 mRNA might contribute to the differential
      regulation of the contractile responses to vasoconstrictors upon LPS exposure.

PMID- 19588735
TI  - Spiritual care in the news.

PMID- 19588736
TI  - Void in spiritual care.

PMID- 19588734
TI  - Role of naturally-occurring plant sterols on intestinal cholesterol absorption
      and plasmatic levels.
AB  - Cardiovascular disease is a major health problem in developed countries although
      its incidence is relatively lower in Mediterranean countries which is partly
      ascribed to dietary habits. Epidemiologic evidence shows that elevated serum
      cholesterol, specifically low-density lipoprotein cholesterol (c-LDL), increases
      cardiovascular disease. Phytosterols are bioactive compounds, found in all
      vegetable foods, which inhibit intestinal cholesterol absorption and, therefore,
      have a serum cholesterol-lowering effect. Intestinal cholesterol absorption is a
      multistep process where plant sterols and stanols may act: a) attenuating the
      NPC1L1 gene expression, which may result in a lower cholesterol uptake from the
      lumen; b) lowering the cholesterol esterification rate by the ACAT2 (acyl-CoA
      cholesterol acyltransferase) and, consequently, the amount of cholesterol
      secreted via the chylomicrons and c) upregulating the expression of ABC
      transporters ABCG5 and ABCG8 in intestinal cells, which may result in an
      increased excretion of cholesterol by the enterocyte back into the lumen. Many
      clinical trials proved that commercial products enriched with phytosterols reduce
      cholesterol levels. Likewise, recent studies show that phytosterols present in
      natural food matrices are also effective and could be an important component of
      cardioprotective dietary patterns such as the Mediterranean diet.

PMID- 19588738
TI  - Mindful attentiveness: rekindling the nurse-patient relationship.

PMID- 19588737
TI  - Disability and the church: how wide is your door?

PMID- 19588739
TI  - Healing abortion: a search for forgiveness.

PMID- 19588740
TI  - Holy ground.

PMID- 19588742
TI  - Freedom of choice: a slippery slope.

PMID- 19588741
TI  - When somebody becomes someone.

PMID- 19588743
TI  - Serving others.

PMID- 19588744
TI  - Nursing in need of transformation: what are we searching for?

PMID- 19588745
TI  - As God opens doors, I follow.

PMID- 19588746
TI  - The importance of right thinking.

PMID- 19588747
TI  - Reflections of excellence.

PMID- 19588748
TI  - No easy answers.

PMID- 19588749
TI  - OK to pray?

PMID- 19588750
TI  - [Surpass expectation: create exquisite periodical].

PMID- 19588751
TI  - [Augmentation of quality of wound healing of deep burn].
AB  - This article summarizes methods of repair of massive and deep wounds, elucidates
      how to improve wound healing quality and avoid scar deformity after deep burn. A
      part of denatured dermis (non-necrotic) in deep partial-thickness burn, "mixed
      degree" burn, even in full-thickness burn wounds before forming eschar can be
      preserved and covered with autologous skin, thereby to avoid secondary damage to
      the structure of subcutaneous tissue and the junction of dermis-adipose, thus to
      result in good functions, appearance, and survival rate. After skin grafting,
      wound healing quality and appearance are improved, joint function and elasticity
      of skin are enhanced, the degree of scar contracture is relieved due to
      preservation of normal adipose tissue after escharectomy. The study of composite
      artificial skin will be actively developed in the future. Tissue-engineering skin
      and stem cells can be successfully used in patients with deep burns for scarless
      healing with restoration of physiological functions in a short period.

PMID- 19588752
TI  - [Repair of deep burn and traumatic wounds in lower extremities with combined
      transplantation of multiple pedicled skin flaps].
AB  - OBJECTIVE: To summarize the clinical experience in repair of deep burn and
      traumatic wounds with combined transplantation of different types of pedicled
      skin flaps in lower extremities. METHODS: Two hundred and thirty-six patients
      with 271 deep wounds in lower extremities after burn or trauma were repaired with
      muscular skin flaps, local fascial flaps and island flaps with vascular pedicle
      (more than 20 types) in our department from Jan. 1998 to Sept. 2008. RESULTS:
      Complete necrosis of skin flaps occurred in 1 case, congestion and necrosis over
      the edge of skin flaps occurred in 3 cases, which were healed after grafting, and
      other skin flaps survived well with soft texture. Skin flaps were too bulky in 26
      cases, among them 17 cases were thinned, and the appearance of other skin flaps
      were satisfactory. In 68 patients with functional region injury were recovered to
      certain extent without contracture. CONCLUSIONS: Skin flaps with pedicles,
      multiple transplantations if necessary, can repair deep wounds satisfactorily in
      lower extremities after deep burn or trauma injury.

PMID- 19588753
TI  - [Surgical therapy for massive deep skin and soft tissue injuries].
AB  - OBJECTIVE: To explore the methods of repair of massive deep skin and soft tissue
      injuries. METHODS: Fifty-six patients with deep skin and soft tissue injuries
      were hospitalized from July 2006 to January 2008. Among them, 23 cases were
      caused by burn, 17 cases by electric injury, 7 cases by hot crush injury, 6 cases
      by avulsion injury, and 3 cases due to other reasons (including traffic accident,
      crush injury, soft tissue infection respectively). Sixty-five skin flaps were
      raised to repair and reconstruct the injured tissues, including 21 local flaps,
      18 distant pedicled skin flaps, and 26 free skin flaps. The area of skin flaps
      ranged from 1.5 cm x 1.0 cm to 39.0 cm x 23.0 cm. RESULTS: Sixty skin flaps
      survived completely, partial necrosis occurred in 3 flaps, and complete necrosis
      in 2 flaps. There was no obvious difference in average survival rate among local
      skin flaps (95.2%), distant pedicled skin flaps (88.8%), and free skin flaps
      (92.3%, P > 0.05). CONCLUSIONS: Skin flap transposition can be still considered
      as the major effective method in repair of massive deep skin and soft tissue
      injury. On the premises of high survival rate, free skin flap transposition can
      be considered as the first choice.

PMID- 19588754
TI  - [Application of thoracic skin flap with multiple blood supply in repair of tissue
      defects and deformities in jaw and neck].
AB  - OBJECTIVE: To explore an appropriate measure to repair tissue defects and
      deformities in mandibulo-cervical region. METHODS: Eighteen cases with severe
      tissue defects and deformity in jaw and neck were repaired with thoracic skin
      flap with multiple blood supply system in our unit from Jan. 2006 to Nov. 2008.
      Anterior cutaneous branch of transverse cervical artery, intercostal branch of
      internal thoracic artery and lateral thoracic artery were included in the
      pedicles. RESULTS: All skin flaps survived, except in one patient in whom a small
      belb appeared at the distal end of the island flap with anterior cutaneous branch
      of transverse cervical artery, and it was healed after a few dressing changes.
      The functions and appearances were satisfactory after 6-month to 2-year follow
      up, without showing secondary deformity. CONCLUSIONS: The blood supply of
      thoracic skin flap is abundant and constant, which is an ideal method for repair
      of tissue defects and deformities in jaw and neck after taking into account some
      factors, such as the demand of the patient, general physical condition, and the
      size of the defect.

PMID- 19588755
TI  - [Application of latissimus dorsi flap in different forms in repair of skin and
      soft tissue defects in lower extremities].
AB  - OBJECTIVE: To explore repair methods of skin and soft tissue defects in lower
      extremities with free latissimus dorsi flaps. METHODS: Forty-two patients with
      wounds and soft tissue defects in lower extremities, including 4 cases on knee,
      22 cases on leg, 15 cases on ankle and foot, 1 case with extensive avulsion from
      knee to dorsum of foot, were hospitalized in our unit from February 1996 to
      February 2008. Wounds or soft tissue defects were respectively repaired with
      latissimus dorsi musculocutaneous flaps, latissimus dorsi muscle flaps,
      latissimus dorsi perforator flaps with preserved vascular sleeves, 2 double-leaf
      segmental latissimus dorsi compound flaps after debridement. The flaps ranged
      from 18 cm x 8 cm to 40 cm x 18 cm in size. The donor sites were covered by skin
      grafting in 19 cases. RESULTS: All wounds were healed primarily except vascular
      crisis occurred in 3 cases, partial necrosis of skin at donor site in 2 cases,
      and graft site (1 case). Follow-up for 3 to 24 months of 31 patients showed: six
      cases received two-stage plastic operation on account of bulkiness with trouble
      in wearing shoes, and mild contraction of muscular flap in 3 cases. CONCLUSIONS:
      Latissimus dorsi flap in various forms can be satisfactory for repair of large
      skin and soft tissue defects in lower extremities.

PMID- 19588756
TI  - [Repair of high-voltage electric burn in jaw and neck region with insular
      pectoralis major myocutaneous flap].
AB  - OBJECTIVE: To evaluate the effect of insular pectoralis major myocutaneous flap
      on repair of jaw and neck tissue defect as a result of high-voltage electric
      burn. METHODS: Eighteen patients with large area tissue defect in jaw and neck
      caused by high-voltage electric burn hospitalized from August 2001 to December
      2007 were repaired with insular pectoralis major myocutaneous flap. The flaps
      (from 12 cm x 10 cm to 16 cm x 13 cm) was transplanted in 8 patients after early
      wound debridement, and in 10 patients on infected wounds. RESULTS: All flaps
      survived wells except in 4 patients necrotic area (length 2-5 cm, width 1-2 cm)
      appeared in the distal wound edge, localized dehiscence of wound edge in 2 cases,
      which were healed after dressing change or secondary suturing. Patients were
      followed up from 6 months to 3 years, and the appearance and function were
      satisfactory. CONCLUSIONS: Pectoralis major muscle island myocutaneous flap has
      the advantage of large tissue mass, with thin and flat muscle belly, and rich
      blood supply, which is suitable for repair of large deep tissue defect in jaw and
      neck.

PMID- 19588757
TI  - [Repair of tissue defect of lower leg and foot with reverse island skin flaps
      with sural nerve and blood supplying vessels].
AB  - OBJECTIVE: To observe the clinical effect of reverse island skin flaps with sural
      nerve and blood supplying vessels on repair of tissue defect of lower leg and
      foot. METHODS: Fifty-six patients with lower leg and foot tissue defects were
      hospitalized from June 1997 to August 2007. Among them, 10 patients suffered from
      soft tissue defect of lower leg; 38 patients suffered from wound infection,
      exposure of fracture of tibia and fibula, and osteonecrosis; 8 patients suffered
      from heelstick tissue defect, bone adhering scar, and osteomyelitis. The defects
      were repaired with sural nerve and blood vessel nourished reverse island skin
      flaps (46 cases) and myocutaneous flaps (10 cases). The size of flaps ranged from
      5 cm x 4 cm to 22 cm x 16 cm. Flap donor sites were closed by direct suture or
      free skin grafting. RESULTS: Flaps in 55 cases survived. Patients were followed
      up 3-6 months, there was no complication, and they were healed with satisfactory
      texture and appearance. The patients could walk normally, but with unsatisfactory
      sensory recovery. In one patient, the flap was broken and ulcerated 1 month after
      operation on account of leaving behind necrotic tibia. It was healed after second
      operation. CONCLUSIONS: Sural nerve and blood vessel nourished reverse island
      skin flap or myocutaneous flap transplantation is an effective treatment for
      repair of soft tissue defect of lower leg and foot.

PMID- 19588758
TI  - [Relationship between Cx40/43 regulating the intracellular Ca2+ concentration of
      vascular smooth muscle cell (VSMC) and endothelium-dependent vascular contractive
      response of superior mesenteric artery in rats].
AB  - OBJECTIVE: To investigate the relationship between intracellular Ca2+
      concentration ([Ca2+]i) mediated by connexin 40/43( Cx40/43) of VSMC and
      endothelium-dependent vascular contractive response of superior mesenteric
      arteries (SMA) in hemorrhagic shock rats. METHODS: Third to fifth passage culture
      of vascular endothelial cells (VEC) and VSMC from SD rats were used as study
      subject, the changes in contractive response of SMA and VSMC against hypoxia were
      observed. The expression of Cx40/43 in SMA,VEC,VSMC were blocked by Cx40/43
      ASODN, then the effect of Cx40/43 on contractive response of hypoxic SMA and
      [Ca2+]i of VSMC were observed. RESULTS: The contractive responses of SMA and VSMC
      after hypoxia were first increased, then decreased. Hypoxia induced calcium
      overload in VSMC [(82 +/- 4)% in normal control group, (115 +/- 8)% in hypoxia
      group at 30 min, (133 +/- 13)% in hypoxia group at 2 h]. Cx40 ASODN increased
      [Ca2+]i in VSMC and contractive response of SMA towards myricetin, while that of
      Cx43 ASODN showed opposite tendency. CONCLUSIONS: Cx40/43 can regulate the SMA
      endothelium-dependent vascular contractive response through [Ca2+]i of VSMC after
      hemorrhagic shock.

PMID- 19588759
TI  - [Effect of lentiviral vector encoding on triggering receptor expressed on myeloid
      cells 1 on expression of inflammatory cytokine in septic mice infected by
      Bacteroides fragilis].
AB  - OBJECTIVE: To investigate the effect of triggering receptor expressed on myeloid
      cells 1 (TREM-1) vshRNA vector on expression of inflammatory cytokines and
      survival rate in septic mice infected by Bacteroides fragilis. METHODS: (1) TREM
      1 vshRNA vector was constructed. Bacteroides fragilis (2.5 x 10(9) CFU/mL, 0.5
      mL) was intraperitoneally injected in each mouse, and septic model was reproduced
      after 12 hours. (2) One hundred and fifteen mice were divided into healthy
      control group (n = 3, HC), sepsis group (n = 28, S), TREM-1 vshRNA group (n = 28,
      T), TREM-1 vshRNA hd group (n = 28, Th), GFP group (n = 28, G) according to
      random number table. Mice in S, T, Th, G groups were firstly injected with
      isotonic saline, TREM-1 vshRNA 2 x 10(8) TU, TREM-1 vshRNA 1 x 10(8) TU, GFP
      siRNA through tail vein, and then sepsis was induced after 1 hour. Mice in HC
      group were injected with equal volume of isotonic saline through tail vein. Three
      mice in each group were sacrificed after 12 hours for determination of plasma
      level of TNF-alpha, IL-1 beta and IL-6, and level of TREM-1mRNA and its protein
      in hepatic tissue. The survival rate of other mice in each group was monitored
      for 72 hours. (3) In 125 mice sepsis was reproduced, among them 100 mice were
      injected with TREM-1 vshRNA 2 x 10(8) TU after 1, 2, 4, 6 hours through tail vein
      (25 mice at each time point), other 25 mice were injected with equal volume of
      isotonic saline as control. The survival rate of mice in each group was recorded
      72 hours after injection. RESULTS: (1) Compared with those in S group, the plasma
      level of TNF-alpha, IL-1 beta and IL-6 lowered in T and Th groups (P < 0.05),
      especially in T group, while those in G group showed no obvious difference (P >
      0.05). (2) Compared with those in G group, the level of TREM-1mRNA and its
      protein in hepatic tissue in T and Th groups decreased (P < 0.01), especially in
      T group. (3) The survival rate of mice in S and G group was 16%, which was
      obviously lower than that in T and Th groups (76%, 44%, respectively, P < 0.05 or
      P < 0.01). (4) The survival rate of mice at 1, 2, 4, 6 hours after injection was
      72%, 56%, 40%, 16%, respectively, while all that except at 6 hour after injection
      were higher significantly than that of control (P < 0.05 or P < 0.01).
      CONCLUSIONS: The intervention with TREM-1 vshRNA can effectively decrease hepatic
      level of TREM-1 in septic mice induced by Bacteroides fragilis, inhibit
      inflammatory response, and improve the survival rate.

PMID- 19588760
TI  - [Effect of intensive insulin therapy on apoptosis-related ligands in serum in
      rats with severe scald].
AB  - OBJECTIVE: To investigate changes in apoptosis-related ligands in serum in rats
      with severe scald and the effect of intensive insulin therapy on the changes.
      METHODS: One hundred and fifty Wistar rats were randomly divided into 3 groups:
      sham burn (SB), scald (S) and treatment (T) groups. Rats in S and T groups were
      inflicted with 40% TBSA full-thickness burn, followed by intraperitoneal
      injection with 40 mL/kg of isotonic saline for resuscitation. Rats in T group
      were subcutaneously injected insulin in a dose of 0.25 U/100 g 24 hours after
      burn injury, and every 12 hours for 5 days (0.25, 0.50, 0.75, 1.00, 1.25 U/100 g
      each day, respectively) to control the level of blood glucose between 3 and 6
      mmol/L. Rats in SB group were sham scalded at 37 degrees C without resuscitation.
      Blood was drawn from abdominal aorta on 1, 4, 7, 10, 14 post burn day (PBD) for
      determination of serum levels of TNF-alpha, soluble Fas ligand (sFasL) and
      soluble Fas receptor (sFas) by enzyme-linked immunosorbent assay (ELISA), and
      insulin by radioimmunity assay (RIA). RESULTS: The serum level of TNF-alpha in S
      group peaked on 1 PBD (30.9 +/- 8.7) ng/L, which showed statistically significant
      difference when compared with that of SB and T groups (12.7 +/- 2.8) ng/L, (16.8
      +/- 4.7) ng/L, respectively, P < 0.01), then lowered gradually to become similar
      to that of SB group on 7 PBD. The level of TNF-alpha in T group increased
      gradually, but was obviously lower than that of S group on 1, 4, 7 PBD (P <
      0.01). The level of sFasL in S (on 7-14 PBD) and T (4-10 PBD) groups was
      significantly higher than that in SB group (P < 0.05), then lowered to normal
      level. The levels of sFas on 4-10 PBD in T group were obviously higher than that
      in S and SB group (P < 0.05). Ratio of sFasL to sFas in serum of S group was
      higher than that in SB group on 7, 10 PBD, which was higher than that in T group
      on 7 PBD (P < 0.05). There was significant decrease in serum level of insulin in
      S group compared with that of SB group on 4-10 PBD (P < 0.05). The level of
      insulin in T group increased on 1 PBD, peaked on 4 PBD (327 +/- 15 microU/mL),
      which was significantly higher than that in SB and S groups (42 +/- 15, 28 +/- 10
      microU/mL, respectively, P < 0.01), then decreased gradually to normal level.
      CONCLUSIONS: Insulin may inhibit apoptosis after burn by down-regulating
      secretion of apoptotic ligands.

PMID- 19588761
TI  - [Relationship between learning and memory ability and expression of hippocampal N
      methyl-D-aspartic acid (NMDA) in burn rats with depression].
AB  - OBJECTIVE: To observe changes of learning and memory ability (LMA) in burn rats
      with depression, and study the relationship between LMA and expression of
      hippocampal NMDA. METHODS: According to simple random method, 46 Wistar rats were
      divided into burn group (B, with 30% TBSA deep partial-thickness burn, n = 10),
      depression group (D, with moderate stress stimulation in chronic and
      unpredictable, n = 12), B + D group (with the same stress stimulation inflicted
      to B group after burn, n = 12), healthy control group ( HC, without treatment, n
      = 12). Changes in escape latency was examined in water maze test. Expression of
      hippocampal NMDA in CA1, CA2 regions and dentate gyrus were observed with
      immunohistochemistry. RESULTS: Compared with that of HC group (22 +/- 20 s),
      water maze escape latency in B, D, B + D groups on 2 day after training prolonged
      (38 +/- 31, 41 +/- 36, 42 +/- 33 s, respectively, P < 0.05 or P < 0.01). Water
      maze escape latency in B + D group on 4th day after training was longer than that
      of other groups (P < 0.01). There was no obvious difference in positive
      expression of NMDA in CA1, CA2 regions among groups (P > 0.05). The positive
      count of NMDA in dentate gyrus in D group (198 +/- 14) and B + D group (191 +/-
      6) were lower than that of HC group (224 +/- 23, P < 0.05 or P < 0.01), but there
      was no obvious difference between HC group and B group (219 +/- 25, P > 0.05).
      CONCLUSIONS: Burn complicated with depression can reduce LMA, which may be due to
      a decrease in NMDA in dentate gyrus.

PMID- 19588762
TI  - [To transdifferentiate human hypertrophic scar fibroblasts induced by connective
      tissue growth factor mediated transforming growth factor-beta 1 in vitro].
AB  - OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF)
      induced TGF-beta 1 in the transdifferentiation of human hypertrophic scar
      fibroblast (HSFb). METHODS: Human hypertrophic scar fibroblasts were cultured in
      vitro, 5 cell samples were stimulated with TGF-beta 1 (0, 2.5, 5.0, 7.5, 10.0
      ng/mL, respectively) for 48 hours; other cell samples were divided into: normal
      control (NC) group, CTGF group (with addition of 10 ng/mL rhCTGF into culture
      medium), TGF-beta 1 group (with addition of 10 ng/mL TGF-beta 1 into culture
      medium), CTGF ASODN group (with addition of 10% FBS-DMEM after transfection of
      CTGF ASODN), CTGF ASODN + TGF-beta 1group (with addition of 10 ng/mL TGF-beta 1
      after transfection of CTGF ASODN). Expression of CTGF was determined by Western
      blotting with stimulation of different concentration of TGF-beta 1. Expression of
      alpha-smooth muscle actin (alpha-SMA) was measured by Western blotting. Positive
      cell rate of alpha-SMA was examined by flow cytometry. RESULTS: With stimulation
      of 10.0 ng/mL TGF-beta 1, the expression of CTGF was obviously higher than that
      of non-stimulation (P < 0.05). Expression of alpha-SMA in the CTGF group and the
      TGF-beta 1 group was obviously higher than that in NC group (P < 0.01), while
      there was no obvious difference among NC, CTGF ASODN, CTGF ASODN + TGF-beta 1
      groups (P > 0.05). The positive cell rate of alpha-SMA in NC, CTGF, TGF-beta 1,
      CTGF ASODN, CTGF ASODN + TGF-beta 1 groups was (10.8 +/- 2.8)%, (29.1 +/- 4.0)%,
      (28.7 +/- 4.8)%, (10.7 +/- 2.3)%, (14.3 +/- 2.9)%, respectively, which was
      similar to expression of alpha-SMA on statistic analysis. CONCLUSIONS: CTGF is
      one of the most important downstream efforts for TGF-beta 1 in inducing the
      transdifferentiation of HSFb.

PMID- 19588763
TI  - [Effect of mastoparan-1 on lipopolysaccharide-induced acute hepatic injury in
      mice].
AB  - OBJECTIVE: To observe the effect of mastoparan-1 (MP-1) on lipopolysaccharide
      (LPS)-induced acute hepatic injury in mice and probe into its possible mechanism.
      METHODS: One hundred and four BALB/c mice were randomly divided into healthy
      control group (n = 8, without treatment, HC), LPS group (n = 48, with injection
      of LPS 5 mg/kg via tail vein), and MP-1 group (n = 48, with injection of LPS 5
      mg/kg and MP-1 3 mg/kg via tail vein). Mice in LPS group and MP-1 group were
      sacrificed at 2nd, 6th, 12th, 24th, 48th and 72nd post injection hour (PIH), 8
      mice at each time point in each group. Blood samples were collected for
      determination of plasma levels of LPS by kinetic turbidimetric limulus test, TNF
      alpha and IL-6 by ELISA, serum levels of ALT and AST by automatic biochemistry
      analyzer respectively. Hepatic tissue samples were collected for determination of
      TLR4, TNF-alpha and IL-6 mRNA by real-time fluorescent quantitation reverse
      transcription polymerase chain reaction, along with the observation of
      pathological changes in hepatic tissue at each time point. Above-mentioned
      examinations were also performed in HC group. RESULTS: Compared with those of HC
      group, plasma levels of LPS and TNF-alpha in LPS group significantly increased at
      2nd PIH (18,320.50 +/- 2782.50 EU/mL and 988 +/- 130 ng/L, respectively), then
      decreased gradually to 1.80 +/- 0.80 EU/mL and 150 +/- 44 ng/L at 72nd PIH, which
      was close to those of HC group. The values of IL-6, ALT and AST peaked at 12th
      PIH, which declined to the levels close to those of HC group at 72nd PIH.
      Meanwhile, the expressions of TLR4, TNF-alpha and IL-6 mRNA in liver were
      remarkably up-regulated after injection, and the pathological changes in hepatic
      tissue pronounced significantly at 12th, 24th and 48th PIH. Compared with those
      of LPS group, the levels of LPS, cytokines, ALT and AST decreased in MP-1 group
      in different degrees after injection (P < 0.05 or P < 0.01), genes expression (P
      < 0.05 or P < 0.01) and pathological changes was respectively suppressed and
      alleviated in hepatic tissue. CONCLUSIONS: MP-1 can alleviate LPS-induced acute
      hepatic injury in mice, which may be associated with its neutralization of LPS
      and attenuation of synthesis and release of inflammatory mediators.

PMID- 19588765
TI  - HPCSA: a mess in the Health Department's pocket.

PMID- 19588764
TI  - [The role of myosin light chain kinase in intestinal epithelial barrier
      dysfunction due to hypoxia].
AB  - OBJECTIVE: To study the role of myosin light chain kinase (MLCK) in intestinal
      epithelial barrier dysfunction after hypoxia. METHODS: The Caco-2 monolayers
      developed with Transwell inserts were exposed to hypoxia for 0 h (NC group), 2,
      6, 8, 12 and 24 h (H group), and 6 h hypoxic specimens were treated with 100
      mol/L ML-9 (T group). The transepithelial electrical resistance (TER) of
      monolayers was measured with an ohmmeter. The tight junction protein ZO-1 of
      monolayers was analyzed by immunofluorescence assay. The protein expressions of
      phosphorylated myosin light chain (p-MLC) and MLCK were detected by Western
      blotting. RESULTS: The TER of monolayers in H group at 6, 8, 12 and 24 h was 422
      +/- 17, 427 +/- 27, 403 +/- 40 and 426 +/- 22 ohms respectively, which was
      significantly lower than that of NC group (451 +/- 27 ohms, P < 0.05). The TER of
      monolayers in T group was 558 +/- 110 ohms, which was significantly higher than
      that in H group at each time point ( P < 0.01). The ZO-1 of monolayers in H group
      at 6 h was irregular in arrangement, with interruptions and rugae, and sawtooth.
      These abnormalities were ameliorated in T group (regular in arrangement, with
      little or without ruga and sawtooth). The protein expressions of p-MLC and MLCK
      in H group at each time point were higher than those in NC group. CONCLUSIONS:
      Intestinal epithelial barrier dysfunction after hypoxia can be mediated by MLCK.

PMID- 19588767
TI  - Perversities--beware of being 'sucked in'.

PMID- 19588769
TI  - Alleged stem cell scam artists face extradition--finally.

PMID- 19588768
TI  - SA medical schools to rescue Zimbabwe's aspirant doctors.

PMID- 19588771
TI  - Pharmaceutical Latin.

PMID- 19588770
TI  - Cutaneous bacillary angiomatosis: a marker of systemic disease in HIV.

PMID- 19588772
TI  - Does the impact factor have too much impact?

PMID- 19588773
TI  - Management of anterior vaginal prolapse in South Africa: national survey.

PMID- 19588775
TI  - Impact of the International Rugby Board's experimental law variations on the
      incidence and nature of match injuries in southern hemisphere professional rugby
      union.
AB  - OBJECTIVE: To examine the epidemiology of match injuries in southern hemisphere
      professional rugby union and assess the impact of the International Rugby Board
      (IRB) Experimental Law Variations. SETTING: One-season whole population
      prospective cohort. SUBJECTS: Twenty-seven teams (813 players) taking part in the
      2008 Super 14 and Vodacom Cup competitions. OUTCOME MEASURES: Incidence,
      severity, location, type and cause of injury. RESULTS: The incidence in the Super
      14 competition (96.3 injuries/1 000 player-match hours; 95% confidence interval
      (CI) 69.0 - 111.7) was significantly higher (p = 0.003) than that in the Vodacom
      Cup (71.2; CI 60.0 - 84.5); injury severity was significantly lower (p < 0.001)
      in the Super 14 (mean 13.4 days; median 5) than the Vodacom Cup (mean 21.2;
      median 12). There were no significant differences between the two competitions in
      type or location of injury: lower limb muscle/ tendon (Super 14: 27.8%; Vodacom
      Cup: 25.7%) and joint (non-bone)/ligament (Super 14: 18.8%; Vodacom Cup: 24.3%)
      were the most common injuries. Injury causation was similar for the two
      competitions but there were significantly fewer ruck/maul (p = 0.001) and more
      tackled (p = 0.010) injuries in Super 14 compared with English Premiership rugby
      and fewer collision (p = 0.002) and more tackling (p < 0.001) injuries compared
      with Rugby World Cup. In the Vodacom Cup, there were significantly more tackling
      (p < 0.001) injuries compared with Rugby World Cup. CONCLUSION: The incidence,
      nature and causes of injuries in southern hemisphere professional club rugby
      played under IRB Experimental Law Variations were similar to those for
      professional club rugby in the northern hemisphere and Rugby World Cup played
      under the previous Laws of Rugby.

PMID- 19588774
TI  - The quest for a groundless surgical procedure.

PMID- 19588776
TI  - Vasectomy under local anaesthesia performed free of charge as a family planning
      service: complications and results.
AB  - OBJECTIVE: To evaluate the safety and efficacy of vasectomy performed under local
      anaesthesia by junior doctors at a secondary level hospital as part of a free
      family planning service. METHOD: Men requesting vasectomy were counselled and
      given written instructions to use alternative contraception until two semen
      analyses 3 and 4 months after vasectomy had confirmed azoospermia. Bilateral
      vasectomy was performed as an outpatient procedure under local anaesthesia by
      junior urology registrars. Statistical analysis was performed using the Mann
      Whitney, Kruskal-Wallis, Fisher's exact or Spearman's rank correlation tests as
      appropriate. RESULTS: Between January 2004 and December 2005, 479 men underwent
      vasectomy at Karl Bremer Hospital, Western Cape, South Africa; their average age
      was 36.1 (range 21 - 66) years, they had a median of 2 (range 0 - 10) children,
      and only 19% had 4 or more children. The average operation time was 15.5 (range 5
      - 53) minutes. Complications occurred in 12.9%; these were pain (7.3%), swelling
      (5.4%), haematoma (1.3%), sepsis (1%), difficulty locating the vas (1%),
      vasovagal episode (0.6%), bleeding (0.6%), wound rupture (0.4%) and dysuria
      (0.2%) (some men had more than one complication). Of the men 63.3% returned for
      one semen analysis and 17.5% for a second. The vasectomy failure rate ranged from
      0.4% (sperm persisting > 365 days after vasectomy) to 2.3% (sperm seen > 180 days
      after vasectomy and/or in the second semen specimen). No pregnancies were
      reported. The complication (5.6%) and failure rates (0%) were lowest for the
      registrar who had performed the smallest number of vasectomies and whose average
      operation time was longest. Comparing the first one-third of procedures performed
      by each of the doctors with the last one-third, there was a significant decrease
      in average operating times but not in complication rates. CONCLUSIONS: Vasectomy
      can be performed safely and effectively by junior doctors as an outpatient
      procedure under local anaesthesia, and should be actively promoted in South
      Africa as a safe and effective form of male contraception.

PMID- 19588777
TI  - Local reference ranges for full blood count and CD4 lymphocyte count testing.
AB  - OBJECTIVE: Recent advances in full blood count and CD4 technology, coupled with
      the changing population demographics of the Gauteng region, have necessitated
      reevaluation of the reference ranges currently in use. METHODS: A cross-sectional
      study of 631 female and 88 male HIV-negative participants from the Gauteng region
      was performed. Full blood count, automated differential and CD4 count analyses
      were done using the latest internationally accepted technology. Reference ranges
      were compiled from the 2.5th and 97.5th percentiles for both male and female
      participant groups, and gender and ethnic comparisons calculated by non
      parametric tests. RESULTS: Results of 41 females were removed from the
      statistical analysis because their results were suggestive of possible anaemia.
      Full blood count reference interval comparison confirmed gender-specific
      differences in red blood cell and platelet parameters. Ethnic-specific
      differences were found for some red blood cell parameters in the black female
      cohort. In addition, black males and females both generally had lower neutrophil
      and higher lymphocyte counts than a combined Asian/Caucasian/coloured ethnic
      group. CONCLUSION: Comparison of the currently calculated reference ranges with
      published data and reference values in use indicated that a separate ethnic
      specific reference range should be introduced for the percentage/absolute
      neutrophil count and percentage lymphocytes. In addition, locally derived
      reference ranges for red cell distribution width (RDW) and CD4 percentage of
      lymphocytes should be implemented for routine diagnostic testing.

PMID- 19588779
TI  - Vaccines for Africa (VACFA) website--an innovative immunisation advocacy tool.

PMID- 19588778
TI  - The incidence and clinical presentation of infantile rotavirus diarrhoea in
      Sierra Leone.
AB  - OBJECTIVES: An effective vaccine is needed to protect against severe rotavirus
      disease, an important cause of gastroenteritis. Since there are no data on the
      incidence and antigenic diversity of rotavirus infection in Sierra Leone, we
      studied its epidemiology to enable an effective vaccine strategy to be designed.
      METHODS: Children between the ages of 3 and 30 months presenting with
      gastroenteritis to the Ola During Children's Hospital in Freetown, Sierra Leone,
      were enrolled. Stool specimens were tested in South Africa using polyacrylamide
      gel electrophoresis to confirm rotavirus infection. RESULTS: Over a 5-month
      period 143 children presenting with gastroenteritis were recruited. Stool samples
      obtained from 128 study subjects were tested for the presence of rotavirus; 45%
      were aged between 3 and 9 months (mean age 10.85 months), and 48 stool samples
      (37.5%) tested positive for rotavirus. The incidence of rotavirus infection was
      20% higher in boys than in girls, a gender difference confirmed elsewhere in West
      Africa. The prevalence of rotavirus-positive stools peaked in August, coinciding
      with the rainy season. About 90% of the rotavirus-positive patients had severe
      diarrhoea, as opposed to only about two-thirds of the patients whose diarrhoea
      was not caused by rotavirus; this difference was statistically significant.
      CONCLUSIONS: There is a high incidence of rotavirus infection in Sierra Leone,
      with rotavirus causing 37.5% of the gastroenteritis in this study. Patients with
      rotavirus gastroenteritis almost all had severe diarrhoea. The high incidence of
      rotavirus infection and the severity of the disease presentation make the
      institution of a rotavirus vaccine programme in Sierra Leone imperative.

PMID- 19588780
TI  - We can train them, but how can we retain them?

PMID- 19588781
TI  - HRT prescriptions linked to 25% of breast cancers in California.

PMID- 19588782
TI  - Free State ARV crisis--central government blamed.

PMID- 19588783
TI  - No pay, no cure--can our hospitals be salvaged?

PMID- 19588784
TI  - Qualified ethics nod to doctors downing tools.

PMID- 19588785
TI  - Bio-ethics vigilance vital: medical and legal doyens.

PMID- 19588786
TI  - Hydatid disease masquerading as an incisional hernia.

PMID- 19588787
TI  - Mao Tse-Tung (1893-1976)--his habits and his health.

PMID- 19588788
TI  - Paediatric liver transplantation in South Africa in 2009.

PMID- 19588789
TI  - Management of cryptoccocal meningitis in resource-limited settings: a systematic
      review.

PMID- 19588790
TI  - Chronic bilateral anterior shoulder dislocation.

PMID- 19588791
TI  - Measles outbreak in South Africa, 2003-2005.
AB  - OBJECTIVES: Measles was virtually eliminated in South Africa following control
      activities in 1996/7. However, from July 2003 to November 2005, 1676 laboratory
      confirmed measles cases were reported in South Africa. We investigated the
      outbreak's cause and the role of HIV. DESIGN: We traced laboratory-confirmed case
      patients residing in the Johannesburg metropolitan (JBM) and O. R. Tambo
      districts. We interviewed laboratory--or epidemiologically confirmed case
      patients or their caregivers to determine vaccination status and, in JBM, HIV
      status. We calculated vaccine effectiveness using the screening method. SETTING:
      Household survey in JBM and O. R. Tambo districts. Outcome measures. Vaccine
      effectiveness, case-fatality rate, and hospitalisations. RESULTS: In JBM, 109
      case-patients were investigated. Of the 57 case-patients eligible for
      immunisation, 27 (47.4%) were vaccinated. Fourteen (12.8%) case-patients were HIV
      infected, 46 (42.2%) were HIV uninfected, and 49 (45.0%) had unknown HIV status.
      Among children aged 12-59 months, vaccine effectiveness was 85% (95% confidence
      interval (CI): 63, 94) for all children, 63% for HIV infected, 75% for HIV
      uninfected, and 96% for children with unknown HIV status. (Confidence intervals
      were not calculated for sub-groups owing to small sample size.) In O. R. Tambo
      district, 157 case-patients were investigated. Among the 138 case-patients
      eligible for immunisation, 41 (29.7%) were vaccinated. Vaccine effectiveness was
      89% (95% CI 77, 95). CONCLUSIONS: The outbreak's primary cause was failure to
      vaccinate enough of the population to prevent endemic measles transmission.
      Although vaccine effectiveness might have been lower in HIV-infected than in
      uninfected children, population vaccine effectiveness remained high.

PMID- 19588792
TI  - Clinical and financial burdens of secondary level care in a public sector
      antiretroviral roll-out setting (G. F. Jooste Hospital).
AB  - BACKGROUND: Antiretroviral therapy (ART) is being extended across South Africa.
      While efforts have been made to assess the costs of providing ART via accredited
      service points, little information is available on its downstream costs,
      particularly in public secondary level hospitals. OBJECTIVES: To determine the
      cost of care for inpatients and outpatients at a dedicated antiretroviral
      referral unit treating and caring for antiretroviral-related conditions in a
      South African peri-urban setting; to identify key epidemiological cost drivers;
      and to examine the associated clinical and outcome data. METHODS: A prospective
      costing study on 48 outpatients and 25 inpatients was conducted from a health
      system perspective. Incremental economic costs and clinical data were collected
      from primary sources at G. F. Jooste Hospital, Cape Town, over a 1-month period
      (March 2005). RESULTS: Incremental cost per outpatient was R1 280, and per
      inpatient R5 802. Costs were dominated by medical staff costs (62% inpatient and
      58% outpatient, respectively). Infections predominated among diagnoses and costs-
      55% and 67% respectively for inpatients, and 49% and 54% respectively for
      outpatients. Most inpatients and outpatients were judged by attending physicians
      to have improved or stabilised as a result of treatment (52% and 59%
      respectively). CONCLUSIONS: The costs of providing secondary level care for
      patients on or immediately preceding ART initiation can be significant and should
      be included in the government's strategic planning: (i) so that the service can
      be expanded to meet current and future needs; and (ii) to avoid crowding out
      other secondary level health services.

PMID- 19588793
TI  - Associations between body mass index and serum levels of C-reactive protein.
AB  - BACKGROUND: Obesity leads to increased risk of cardiovascular disease and glucose
      intolerance, which are phenomena of chronic inflammation. This study was
      performed to determine whether a higher body mass index (BMI) and central obesity
      are associated with low-grade inflammation. METHODS: An analysis of 8 453 adults
      aged > or =20 years was performed. Every subject completed a household interview
      and a questionnaire regarding personal health, and their BMI and serum C-reactive
      protein (CRP) level were measured. The BMI data were divided into quintiles,
      using multiple linear regression to estimate the relationship between CRP level
      and BMI quintiles. An extended-model approach was used for covariate adjustment.
      The association between central obesity and CRP level was examined by this method
      as well. RESULTS: After controlling for demographics, chronic diseases, health
      behaviours and levels of folate and vitamin B12, the beta coefficient (which
      represents the change of natural-log-transformed levels of CRP for each kg/m2
      increase in BMI) was 0.078 (p < 0.001). The CRP levels also increased across
      increasing quintiles of BMI (p for trend <0.001). The beta coefficient,
      representing the change of natural-log-transformed levels of CRP comparing
      subjects with central obesity to those without, was 0.876 (p < 0.001).
      CONCLUSION: Higher BMIs as well as central obesity are independently associated
      with higher levels of CRP.

PMID- 19588794
TI  - Metabolic syndrome and obesity among workers at Kanye Seventh-Day Adventist
      Hospital, Botswana.
AB  - INTRODUCTION: Metabolic syndrome and obesity are risk factors for developing type
      2 diabetes mellitus and/or cardiovascular disease, especially stroke. There is
      evidence worldwide of the high prevalence of these pathologies in health care
      providers. OBJECTIVES: To determine the frequency of metabolic syndrome,
      overweight, obesity and risk of developing metabolic syndrome in workers at Kanye
      Seventh-day Adventist Hospital, Kanye, Botswana. METHODS: An observational and
      cross-sectional study. For the detection of metabolic syndrome, the criteria of
      the Adult Treatment Panel III were used; for obesity, the body mass index of 150
      workers was applied. Data were grouped and analysed according to gender, age and
      type of work. RESULTS: Thirty-four per cent of the hospital's workers had
      metabolic syndrome, the same percentage were at high risk of developing metabolic
      syndrome, 28.7% were obese, and 27.3% were overweight. Female gender was found to
      be strongly associated with obesity and metabolic syndrome. The age group of 35
      54 years was most affected. CONCLUSIONS: There is a high prevalence of obesity
      and metabolic syndrome among Kanye Seventh-day Adventist Hospital workers. We
      recommend the implementation of programmes to screen these risk factors by means
      of routine medical exams and improving the lifestyles of Botswana health care
      workers. The study findings could be the basis for future research among hospital
      staff and the general population.

PMID- 19588795
TI  - The South African Stress and Health (SASH) study: a scientific base for mental
      health policy.

PMID- 19588796
TI  - The South African Stress and Health (SASH) study: 12-month and lifetime
      prevalence of common mental disorders.
AB  - BACKGROUND: The South African Stress and Health (SASH) study is the first large
      scale population-based study of common mental disorders in the country. This
      paper provides data on the 12-month and lifetime prevalence of these conditions.
      METHODS: Data from a nationally representative sample of 4351 adults were
      analysed. Mental disorders were assessed with the Composite International
      Diagnostic Interview (CIDI). An extensive survey questionnaire detailed
      contextual and socio-demographic factors, onset and course of mental disorders,
      and risk factors. Simple weighted cross-tabulation methods were used to estimate
      prevalence, and logistic regression analysis was used to study correlates of 12
      month and lifetime prevalence. RESULTS: The lifetime prevalence for any disorder
      was 30.3%, and the most prevalent 12-month and lifetime disorders were the
      anxiety disorders. The Western Cape had the highest 12-month and lifetime
      prevalence rates, and the lowest rates were in the Northern Cape. CONCLUSIONS:
      The SASH study shows relatively high 12-month and lifetime prevalence rates.
      These findings have significant implications for planning mentalhealth services.

PMID- 19588797
TI  - Mental health service use among South Africans for mood, anxiety and substance
      use disorders.
AB  - BACKGROUND: Europe and North America have low rates of mental health service use
      despite high rates of mental disorder. Little is known about mental health
      service use among South Africans. DESIGN: A nationally representative survey of
      4351 adults. Twelve-month DSM-IV (Diagnostic and Statistical Manual, 4th edition)
      diagnoses, severity, and service utilisation were determined using the World
      Health Organization Composite International Diagnostic Interview (CIDI). Twelve
      month treatment was categorised by sector and province. South Africans in
      households and hostel quarters were interviewed between 2002 and 2004 in all nine
      provinces. OUTCOME MEASURES: 4 317 respondents 18 years and older were analysed.
      Bivariate logistic regression models predicted (i) 12-month treatment use of
      service sectors by gender, and (ii) 12-month treatment use by race by gender.
      RESULTS: Of respondents with a mental disorder, 25.2% had sought treatment within
      the previous 12 months; 5.7% had used any formal mental health service. Mental
      health service use was highest for adults with mood and anxiety disorders, and
      among those with a mental disorder it varied by province, from 11.4% (Western
      Cape) to 2.2% (Mpumalanga). More women received treatment, and this was largely
      attributable to higher rates of treatment in women with mood disorders. Age,
      income, education and marital status were not significantly associated with
      mental health service use. Race was associated with the treatment sector accessed
      in those with a mental disorder. CONCLUSIONS: There is a substantial burden of
      untreated mental disorders in the South African population, across all provinces
      and even in those with substantial impairment. Greater allocation of resources to
      mental health services and more community awareness initiatives are needed to
      address the unmet need.

PMID- 19588798
TI  - Impact of common mental disorders during childhood and adolescence on secondary
      school completion.
AB  - There are few data from South Africa and other low- and middle-income countries
      on how mental disorders in childhood and adolescence may influence different
      aspects of socio-economic position, including educational attainment. We examined
      the association between early-onset disorders and subsequent educational
      achievement in a nationally representative sample of 4 351 South African adults.
      After adjusting for participant demographic characteristics and traumatic life
      events, post-traumatic stress disorder, major depressive disorder and substance
      related disorders were each associated with increased odds of failing to complete
      secondary education (odds ratios and 95% confidence intervals 2.3, 1.0-5.1; 1.7,
      1.2-2.5, and 1.7, 1.2-2.5, respectively). These data point to the role that early
      life mental disorders may play in educational achievement and subsequent socio
      economic position over the life course.

PMID- 19588799
TI  - Patterns of substance use in South Africa: results from the South African Stress
      and Health study.
AB  - BACKGROUND: There are limited data on substance use in South Africa. We describe
      patterns of substance use based on recent, nationally representative data.
      METHODS: Data were derived from the 2002-2004 South African Stress and Health
      (SASH) study. A nationally representative household probability sample of 4351
      adults was interviewed using the paper and pencil version of the World Health
      Organization Composite International Diagnostic Interview (CIDI). Data are
      reported for lifetime use, socio-demographic correlates of use, and age of cohort
      predicting lifetime use for four classes of drugs. RESULTS: The estimate for
      cumulative occurrence of alcohol use was 38.7%, of tobacco smoking 30.0%, of
      cannabis use 8.4%, of other drug use 2.0%, and of extra-medical psychoactive drug
      use 19.3%. There were statistically significant associations between male gender
      and alcohol, tobacco, cannabis and other drug use. Coloureds and whites were more
      likely than blacks to have used alcohol, tobacco and other drugs. Clear cohort
      variations existed in the age of initiation of drug use; these were most marked
      for other drugs and for extra-medical drug use. Use of all drug types was much
      more common in recent cohorts, with a similar cumulative incidence of tobacco,
      alcohol and cannabis use across age cohorts. CONCLUSIONS: Epidemiological
      patterns of use for alcohol, tobacco, cannabis, other drugs and extra-medical
      drugs provide the first nationally representative data. New findings on race and
      exploratory data on time trends provide a foundation for future epidemiological
      work on drug use patterns across birth cohorts and population subgroups in South
      Africa.

PMID- 19588800
TI  - The epidemiology of major depression in South Africa: results from the South
      African stress and health study.
AB  - BACKGROUND: Mental disorders are a major contributor to the burden of disease in
      all regions of the world. There are limited data on the epidemiology of major
      depressive disorder in South Africa. METHODS: A nationally representative
      household survey was conducted between 2002 and 2004 using the World Health
      Organization Composite International Diagnostic Interview (CIDI) to establish a
      diagnosis of depression. The dataset analysed included 4351 adult South Africans
      of all racial groups. RESULTS: The prevalence of major depression was 9.7% for
      lifetime and 4.9% for the 12 months prior to the interview. The prevalence of
      depression was significantly higher among females than among males. The
      prevalence was also higher among those with a low level of education. Over 90% of
      all respondents with depression reported global role impairment. CONCLUSION: In
      comparison with data from other countries, South Africa has lower rates of
      depression than the USA but higher rates than Nigeria. The findings are broadly
      consistent with previous findings in South Africa. These findings are the first
      step in documenting a level of need for care in a context of significant under
      funding of mental health services and research in South Africa

PMID- 19588801
TI  - Life stress and mental disorders in the South African stress and health study.
AB  - BACKGROUND: Although stressful life events (SLEs) are associated with
      psychopathology, the contribution from distal and proximal events and the
      specificity of their association with common mental disorders require further
      exploration. We examined the association of recent life events and past
      adversities to mood, anxiety, substance use and impulse control disorders in
      South Africa. METHODS: Data were analysed from the South African Stress and
      Health study, a population-based study of mental disorders in a nationally
      representative sample of 4 351 adults. Psychiatric disorders were assessed with
      the Composite International Diagnostic Interview (CIDI). This included questions
      covering early and later SLEs (negative life events, relationship stress, partner
      violence, social strain and adverse events during childhood) and various
      sociodemographic variables. Logistic regression models were constructed for 3957
      respondents (2371 female, 1586 male) with no missing covariate data, to assess
      life stress and sociodemographic predictors of 12-month and lifetime disorder.
      RESULTS: Recent negative life events and relationship problems were significant
      predictors of any 12-month disorder and any lifetime disorder. Physical partner
      violence predicted any lifetime disorder. There was evidence of specificity for
      the prediction of mood versus anxiety disorders, with childhood adversity
      specifically associated with mood disorders but not anxiety disorders. Single
      marital status was the strongest socio-demographic predictor of any 12-month and
      any lifetime disorder. CONCLUSIONS: Stressful life events, distal and proximal,
      contribute significantly and independently to the prediction of major psychiatric
      disorders among South Africans, underscoring the importance of screening
      adversities in adults with common mental disorders, and of providing appropriate
      adjunctive interventions.

PMID- 19588802
TI  - Perceived discrimination and mental health disorders: the South African Stress
      and Health study.
AB  - OBJECTIVES: To describe the demographic correlates of perceived discrimination
      and explore the association between perceived discrimination and psychiatric
      disorders. DESIGN: A national household survey was conducted between 2002 and
      2004 using the World Health Organization Composite International Diagnostic
      Interview (CIDI) to generate diagnoses of psychiatric disorders. Additional
      instruments provided data on perceived discrimination and related variables.
      SETTING: A nationally representative sample of adults in South Africa. SUBJECTS:
      4351 individuals aged 18 years and older. OUTCOMES: 12-month and lifetime mood,
      anxiety and substance use disorders. RESULTS: In the multivariate analyses, acute
      and chronic racial discrimination were associated with an elevated risk of any 12
      month DSM-IV disorder when adjusted for socio-demographic factors, but this
      association was no longer statistically significant when adjusted for other
      sources of social stress. In fully adjusted models, acute racial discrimination
      was associated with an elevated risk of lifetime substance use disorders. Acute
      and chronic non-racial discrimination were associated with an elevated risk of 12
      month and lifetime rates of any disorder, even after adjustment for other
      stressors and potentially confounding psychological factors. The association of
      chronic non-racial discrimination and 12-month and lifetime disorder was evident
      across mood, anxiety, and substance use disorders in the fully adjusted models.
      CONCLUSION: The risk of psychiatric disorders is elevated among persons who
      report experiences of discrimination. These associations are more robust for
      chronic than for acute discrimination and for non-racial than for racial
      discrimination. Perceived discrimination constitutes an important stressor that
      should be taken into account in the aetiology of psychiatric disorders.

PMID- 19588805
TI  - Tracking nurses' every move.

PMID- 19588804
TI  - DSM-IV-defined common mental disorders: association with HIV testing, HIV-related
      fears, perceived risk and preventive behaviours among South African adults.
AB  - BACKGROUND: There are few reports from South Africa on how common mental
      disorders may be associated with HIV-related perceptions and behaviours. METHODS:
      Between 2002 and 2004, 4351 South African adults were interviewed. Psychiatric
      diagnoses of depression, anxiety and substance abuse disorders were based on the
      Diagnostic and Statistical Manual, 4th edition (DSM-IV). HIV-related fears,
      perceived risk and behaviour change were measured using multi-item scales. We
      analysed forms of behaviour change that were appropriate for risk reduction (such
      as changes in sexual behaviour) separately from behaviour changes that were
      inappropriate to prevent HIV (such as care over things touched or avoiding
      certain social situations). RESULTS: The presence of any DSM-IV-defined disorder
      during the previous 12 months was associated with previous HIV testing, increased
      HIV-related fears, and high levels of perceived risk of HIV. There were no
      associations between depression, anxiety and substance abuse disorders and
      appropriate forms of behaviour change for HIV risk reduction. However,
      individuals with an anxiety or a depressive disorder were more likely to report
      inappropriate forms of behaviour change. For example, individuals with any
      depressive and/or anxiety disorders were 1.57 and 1.47 times more likely,
      respectively, to report avoiding certain social situations to prevent HIV/AIDS
      compared with those who did not have such disorders (p < 0.01 for both
      associations). DISCUSSION: The lack of appropriate forms of behaviour change to
      prevent HIV transmission, despite increased levels of HIV-related fear and
      perceived risk, underscores the need for HIV risk reduction interventions for
      individuals living with common mental disorders in South Africa.

PMID- 19588803
TI  - Perpetration of gross human rights violations in South Africa: association with
      psychiatric disorders.
AB  - BACKGROUND: A nationally representative study of psychiatric disorders in South
      Africa provided an opportunity to study the association between perpetration of
      human rights violations (HRVs) during apartheid and psychiatric disorder. Prior
      work has suggested an association between perpetration and post-traumatic stress
      disorder (PTSD), but this remains controversial. METHODS: Subjects reported on
      their perpetration of human rights violations, purposeful injury, accidental
      injury and domestic violence. Lifetime and 12-month prevalence of DSM-IV
      (Diagnostic and Statistical Manual, 4th edition) disorders were assessed with
      Version 3.0 of the World Health Organization Composite International Diagnostic
      Interview (CIDI 3.0). Socio-demographic characteristics of these groups were
      calculated. Odds ratios for the association between the major categories of
      psychiatric disorders and perpetration were assessed. RESULTS: HRV perpetrators
      were more likely to be male, black and more educated, while perpetrators of
      domestic violence (DV) were more likely to be female, older, married, less
      educated and with lower income. HRV perpetration was associated with lifetime and
      12-month anxiety and substance use disorders, particularly PTSD. Purposeful and
      DV perpetration were associated with lifetime and 12-month history of all
      categories of disorders, whereas accidental perpetration was associated most
      strongly with mood disorders. CONCLUSION: Socio-demographic profiles of
      perpetrators of HRV and DV in South Africa differ. While the causal relationship
      between perpetration and psychiatric disorders deserves further study, it is
      possible that some HRV and DV perpetrators were themselves once victims. The
      association between accidental perpetration and mood disorder also deserves
      further attention.

PMID- 19588806
TI  - Healthcare reform: out of the crystal ball and onto the printed page.

PMID- 19588807
TI  - Strategies for ensuring an IT project delivers value.
AB  - To ensure an IT project delivers its promised value, a healthcare organization
      should: Develop a sound project plan. Assign effective sponsors to the project.
      Ensure capable project management. Establish organizational management of value
      delivery.

PMID- 19588808
TI  - A collaborative approach to improving revenue integrity.
AB  - In the area of pharmacy services, Kingman Regional's revenue integrity program
      has enabled the hospital to: Efficiently capture facility-administered
      pharmaceutical charges at the appropriate rate. Maintain efficient administrative
      oversight of pharmacy procurement, dispensing, and billing. Automate the transfer
      of data between various revenue systems within and outside the pharmacy.

PMID- 19588809
TI  - Healthcare reform: a moral imperative, an economic necessity.

PMID- 19588810
TI  - Healthcare reform: it can be done.

PMID- 19588811
TI  - Making the right decisions in a consolidating market.
AB  - Market forces may lead to increased consolidation in the healthcare industry,
      creating both opportunities and challenges. Opportunities for small hospitals and
      health systems include partnering with stronger organizations, while for larger
      organizations, acquiring potentially undervalued hospitals can yield the benefits
      associated with increased size and scale. Potential barriers to success arise in
      three areas-strategy, finance, and operations. Healthcare executives must
      understand and be willing to fully address these challenges.

PMID- 19588812
TI  - Tripping debt covenants.
AB  - In the current economy, many hospitals are changing their debt structure or
      taking on new debt. Healthcare financial managers should avoid tripping their
      debt covenants by creating a risk budget that includes covenant considerations.
      Tactical management of the risk budget may be necessary and requires
      understanding how decisions and market influences affect both sides of the
      balance sheet.

PMID- 19588813
TI  - Medicare RACs: how should hospitals prepare?
AB  - Medicare's Recovery Audit Contractor (RAC) program is being rolled out nationwide
      in 2009. To successfully manage the RAC appeals process, hospital revenue cycle
      leaders require accurate and timely tracking of all RAC-related events,
      deadlines, findings, and costs. These leaders also need to take steps to avoid
      Medicare overpayments, including establishing mechanisms at the point of billing
      to prevent inappropriate claim submissions to Medicare.

PMID- 19588814
TI  - Aligning risk management with patient safety.
AB  - There are four key components to the success of HCCI, a captive insurance company
      formed by five healthcare systems: Common and aligned goals. A commitment to
      ongoing education. Open and honest dialogue among member-owners. Easy-to-use
      technology to support information flow and decision making.

PMID- 19588815
TI  - The "red flags" rule in health care.
AB  - Important questions for hospitals to ask regarding the Federal Trade Commission's
      identity theft "red flags" rule include: What is the compliance deadline? Who
      must comply? What is required for compliance? What about HIPAA? What are the
      consequences of failure to comply?

PMID- 19588816
TI  - Something old is something new again: structuring physician practice
      acquisitions.
AB  - A physician employment contract should give careful consideration to: Hours of
      practice. Control that can be exercised by the hospital. The ability of the
      hospital to relocate the physician's practice. Compensation formulas and
      benefits. Covenants not to compete.

PMID- 19588817
TI  - Paying for call coverage: what you should know.
AB  - Hospitals are finding they must pay for call coverage because of physician's
      growing unwillingness to provide such coverage without compensation. In light of
      a July 2007 Office of Inspector General advisory opinion and federal regulations
      surrounding payments to physicians, it is critically important that call coverage
      arrangements be structured appropriately and at a fair market value (FMV) rate.
      Failure to set compensation at FMV could result in criminal and/or civil
      penalties based on healthcare fraud and abuse laws.

PMID- 19588818
TI  - Checklist for materials management supply contracts.

PMID- 19588819
TI  - The not-so-tech-savvy workforce--and what we can do about it.

PMID- 19588820
TI  - [Intraoperative graft assessment using fluorescent imaging system (SPY)].
AB  - We investigated the efficacy of intraoperative fluorescent imaging system for the
      assessment of coronary artery bypass grafting (CABG). We used SPY imaging system
      in 100 CABG (57 off-pump and 43 on-pump CABG), totalling 287 distal anastomoses.
      The total graft patency rate on postoperative angiography in this series was
      96.2% (276/287). Graft revision was done in 10 cases (10.0%) and 13 anastomoses
      (4.5%) by SPY imaging, which all resulted in good patency at postoperative
      angiography. On the other hand, 7 distal anastomoses and 1 mammary graft (2.8%)
      appeared to be successful on intraoperative SPY imaging, but were revealed to be
      occluded by postoperative angiography. SPY imaging system is useful for graft
      validation, and may contribute to improvement of coronary bypass graft patency.

PMID- 19588821
TI  - [Evaluation of airway obstruction compressed by thoracic great vessels or their
      branches using multi-slice helical computed tomography].
AB  - Airway obstruction due to compression by the thoracic great vessels or their
      branches sometimes appears in patients with congenital heart disease. However, to
      make a definitive diagnosis may not be easy, because respiratory symptoms are
      common and stem from a variety of causes in this cohort. Thus, some invasive
      evaluation, including angiography, bronchial fiberscopy, and bronchography has
      usually been required. We employed multi-slice helical computed tomography (MSCT)
      and 3-dimensional (3D) image reconstruction in 7 cases (median age, 107 days ;
      range, 21 days to 6 years) who were suspected of complicating external vascular
      compression as a cause of respiratory symptoms. The CT scan clearly showed
      detailed anatomy of the thoracic vessels and interrelationship with the airway
      systems. It also disclosed a culprit artery compressing the trachea or bronchus.
      Different from other invasive or noninvasive examination modalities, MSCT allows
      precise evaluation of 2 independent organ systems, such as vascular and
      respiratory systems. We conclude that MSCT with 3D image reconstruction
      represents a reliable less-invasive technique for assessment of symptomatic
      airway obstruction caused by vascular compression.

PMID- 19588822
TI  - [Noonan syndrome with atrial septal defect and hypertrophic cardiomyopathy].
AB  - Noonan syndrome is one of the most common nonchromosomal syndromes seen in
      children with congenital heart disease. The major cause of death is congestive
      heart failure. We report a case of Noonan syndrome with hypertrophic
      cardiomyopathy and arterial septal defect (ASD). Since 10 years old he had been
      suffering from congestive heart failure. ASD patch closure with a fenestrated
      flap valve patch was performed at 12 years of age. After operation, left-to-right
      shunt flow through the patch gradually decreased and he was discharged at 19
      postoperative day in good condition.

PMID- 19588823
TI  - [Aortic valve replacement and hemiarch replacement in a patient with a porcelain
      aorta].
AB  - We report a case of aortic valve replacement and hemiarch replacement with
      reconstruction of the brachiocephalic artery in a patient with a porcelain aorta.
      A 65-year-old man was admitted to the hospital for aortic stenosis. Computed
      tomography demonstrated severe aortic calcification and extensive calcification
      covering a wide area of the aorta. The echocardiography showed a highly calcified
      aortic valve and a pressure gradient of 109 mmHg across the aortic valve. At
      surgery, calcification of the ascending aorta was severe and involved its entire
      circumference. Therefore, 2 cannulae were inserted to the right axillary and
      right femoral arteries for extracorporeal circulation. We performed replacement
      of the ascending aorta and hemiarch with reconstruction of the brachiocephalic
      artery under circulatory arrest and antegrade cerebral perfusion, as well as
      aortic valve replacement with a 21 mm St. Jude Medical mechanical valve. He had
      no major cardiac complications during the postoperative course, and was
      discharged on postoperative day 33.

PMID- 19588824
TI  - [Complete resection of an advanced mediastinal nonseminomatous germ cell tumor
      with multiple distant metastases after down-staging by chemotherapy].
AB  - A mediastinal nonseminomatous germ cell tumor was completely resected after down
      staging by chemotherapy despite the presence of multiple distant metastases. A 22
      year-old female was admitted for superior vena cava (SVC) syndrome. Her SVC was
      obstructed by a large anterior mediastinal tumor; she also exhibited distant
      metastases on a left rib, in the liver, and multiple in the lung. The blood alpha
      fetoprotein (AFP) level was extremely elevated to 57,530 ng/ml. Four courses of
      BEP therapy [cisplatin (CDDP), bleomycin (BLM), etoposide (VP-16)] and a high
      dose chemotherapy followed by a peripheral blood stem cell transplantation made
      the tumor become smaller and effected its down-staging. Residual mediastinal
      tumor with an intravascular tumor in SVC was completely resected. The SVC was
      reconstructed by an artificial vessel graft. A mediastinal nonseminomatous germ
      cell tumor, even though it has multiple distant metastases, can achieve down
      staging and complete resection by a chemotherapy based on scientific evidence.

PMID- 19588825
TI  - [Malignant pleural mesothelioma in which many asbestos bodies were counted in its
      specimen].
AB  - A 53-years-old woman was admitted to our hospital because of pleural effusion.
      She underwent pleural biopsy and diagnosed as mesothelioma. Right
      extrapleuralpneumonectomy was performed. We counted asbestos bodies in the
      resected lung. 443,571 asbestos bodies were counted in 1 gram of dry lung. We
      thought that she was heavily exposed to asbestos. Since high risk of incidence of
      mesothelioma is suggested among her fellow worker, special investigation is
      necessary for asbestos exposure.

PMID- 19588826
TI  - [Surgically treated chest wall schwannoma without entering the pleural space
      utilizing ultrasonography].
AB  - We report a case of surgically treated chest wall schwannoma without entering the
      pleural space utilizing ultrasonography. A 19-year-old woman was admitted for an
      abnormal shadow on a routine health checkup. Roentgenologic examination of the
      chest showed a 2 cm left chest wall mass. Chest computed tomography revealed a
      heterogeneous mass with obtuse angles characteristic of a pleural-based lesion.
      Under general anesthesia, the patient was placed in the right decubitous
      position. Chest wall ultrasonography defined a mass in the intercostal space. A
      2.5 cm skin incision was made on the tumor. The tumor arising from the
      intercostal nerve was surgically removed without entering the pleural space. The
      pathological examination revealed a benign schwannoma. Postoperative course was
      uneventful and she discharged 2 days later. Six years later the patient is well
      without recurrence.

PMID- 19588827
TI  - [Emergency distal arch replacement for traumatic thoracic aortic dissection with
      subarachnoid hemorrhage].
AB  - A 77-year-old woman was transferred as traumatic thoracic aortic dissection with
      subarachnoid hemorrhage soon after a traffic accident. Her consciousness was
      slightly compromised and cardiogenic shock was developed. Serial computed
      tomography (CT) scans revealed an unchanging subarachnoid hemorrhage and a
      progressive mediastinal hemorrhage and pericardial effusion due to traumatic type
      B aortic dissection. An emergency distal arch replacement was performed under
      cardiopulmonary bypass 4 hours after the injury. She woke up 3 days after the
      operation without progression of subarachnoid hemorrhage on a cerebral CT scan.
      She was discharged 36 days after the injury.

PMID- 19588828
TI  - [Konno procedure for congenital aortic stenosis associated with complex left
      ventricular outflow tract obstruction].
AB  - Two successful cases of Konno procedure for congenital aortic stenosis and left
      ventricular outflow tract obstruction (LVOTO) were reported herein. A 3-year-old
      child previously underwent definitive repair of complete atrioventricular septal
      defect. Follow-up echocardiography revealed progression of valvular aortic
      stenosis and subaortic tunnel stenosis. Second patient was a 30-year-old male
      with congenital aortic stenosis, severe LVOTO and funnel chest. Both patients
      underwent Konno procedure, and their postoperative courses were uneventful. The
      Konno procedure is effective and stenotic lesion could be enlarged sufficiently
      even in complex LVOTO. Especially in the patient of advanced age, care should be
      taken to fragility of the left ventricular muscle and coronary malperfusion
      caused by the procedure itself.

PMID- 19588830
TI  - [Lymphangiomyomatosis pathologically diagnosed by surgery for pneumothorax].
AB  - We report a case of incipient pulmonary lymphangioleiomyomatosis (LAM) diagnosed
      by histopathological examination of excised lung. A 28-year-old woman was
      referred to our hospital because of recurrent left pneumothorax. Computed
      tomography showed no abnormality except for small bullae in the right middle
      lobe. She underwent video-assisted thoracoscopic surgery and we excised the apex
      of the left lung showing hypertrophic pleura. Microscopic examinations of the
      surgical specimen revealed multiple focal accumulations of small spindle-shaped
      cells stained positively with anti-HMB-45 antibody, specific for LAM.
      Furthermore, among these multiple lesions, vascular invasion of HMB-45 positive
      cells were observed, which demonstrates invasive and metastatic potential of LAM
      cells as previously reported. This case implicates a need for a careful
      pathological examination of excised specimens in female cases of surgically
      treated pneumothorax even though pre-operation or macroscopic examination shows
      no specific findings.

PMID- 19588829
TI  - [Metastatic lung cancer origin from osteosarcoma of mandible invading tracheal
      lumen].
AB  - A 52-year-old woman underwent the surgical treatment for osteosarcoma of the left
      mandible in 2003 and was followed up afterward. She suffered from dry cough and
      bloody sputum, and was admitted to our hospital in April 2007. Computed
      tomography (CT) revealed several nodules in bilateral lung, and bronchofiberscopy
      showed the endobronchial tumor obstructing in the right main bronchus. The
      metastatic tumor progressed in the right main bronchus from the right S6 lung
      segment. The tumor rapidly progressed in the right bronchus in comparison with
      the CT findings in about 2 weeks, and the possibility of the tracheal obstruction
      was considered. She underwent the right middle and lower lobectomy, and the
      endobronchial tumor was pulled through the right main bronchus. The postoperative
      course was uneventful, the patient was discharged on 14th postoperative day, and
      the chemotherapy using cisplatin (CDDP) and adriamycin (ADR) is on-going.

PMID- 19588831
TI  - [Thoracic aortic aneurysm associated with pseudocoarctation; report of a case].
AB  - A 20-year-old woman without any significant history of disease was referred for
      further investigation of an aortic arch aneurysm. The arterial blood pressure in
      the right arm was higher than in the left arm and in both legs. An multi-detector
      row computed tomography (MDCT) and an aortogram revealed narrowing of the middle
      aortic arch, kinking at the ligamentum arteriosum, subsequent multiple aneurysmal
      formation, and stenosis and narrowing of the descending aorta. The left
      subclavian artery branched from the 1st aneurysm. We resected the aneurysms and
      reconstructed the distal aortic arch and left subclavian artery using a woven
      polyester graft. This case was diagnosed as thoracic aortic aneurysm associated
      with pseudocoarctation, which is a quite rare congenital anomaly.

PMID- 19588832
TI  - [Aortic dissection after aortic valve replacement with an aorto-left atrial
      fistula; report of a case].
AB  - Aortocameral fistula is a rare complication of aortic dissection. We herein
      report a case of aortic dissection after aortic valve replacement (AVR)
      complicated with a fistula to the left atrium. A 76-year-old man who had
      undergone AVR 1 year previously, was admitted to our hospital because of facial
      edema and chest discomfort. On auscultation, a continuous murmur was heard at the
      left lower sternal border. Computed tomography revealed dissecting aneurysm of
      the ascending aorta and a fistula to the left atrium was suspected.
      Transesophageal echocardiography showed the fistula between the false lumen of
      the aneurysm and the left atrium. Ascending aorta replacement and closure of the
      fistula was performed. There was dense adhesion between the aortic root and the
      roof of the left atrium. It seems that postoperative adhesion plays an important
      role in formation of aortocameral fistula.

PMID- 19588833
TI  - [Combined pulmonary resection and cardiac operation; report of a case].
AB  - A 59-year-old woman was admitted because of an abnormal shadow on the chest X-ray
      film. Transbronchial lung biopsy revealed adenocarcinoma of the right lung, and
      chest computed tomography showed left atrial tumor. First, we performed a
      resection of left atrial tumor (myxoma) under cardiopulmonary bypass (CPB),
      followed by a right upper lobectomy with lymph node dissection. The postoperative
      course was uneventful, and she was discharged on the 14th postoperative day. It
      is safe and efficient that pulmonary resection and cardiac operation under CPB
      are surgically treated in a one-stage operation.

PMID- 19588835
TI  - [Early malignant pleural mesothelioma; report of a case].
AB  - We report a case who had undergone operation of very early malignant pleural
      mesothelioma (MPM). A 58-year-old woman admitted to first visited hospital
      because of pleural effusion of the right side. She received a diagnosis of
      epithelial type MPM which had been confirmed from a pleural biopsy spacemen
      obtained by thoracoscopy under local anesthesia. An abnormal change of the pleura
      could not be detected on chest X-ray and thoracic computed tomography (CT) scan
      after chest drainage. She was referred to our hospital for surgery, and was
      undergone an extrapleural pneumonectomy followed by postoperative treatment with
      cisplatin puls gemcitabine. Pathologically, the disease was diagnosed as stage IA
      based on the classification of International Mesothelioma Interest Group (IMIG).
      There is a no evidence of the relapse 9 months after the operation. An early
      diagnosis of the MPM is very difficult. The thoracoscope with local anesthesia
      was very effective for early diagnose of a MPM.

PMID- 19588834
TI  - [Metastatic ectopic cervical thymoma with prolonged survival; report of a case].
AB  - A 60-year-old woman presented with a palpable and painful nodule of her neck.
      Physical examination revealed that the anterior neck mass was enlarged without
      other positive findings. The tumor was not diagnosed with a fine needle
      aspiration biopsy, so that the excision of the tumor was underwent. The diagnosis
      at permanent section analysis revealed a non-invasive thymoma. The patient did
      not receive adjunctive postoperative therapy. For the duration of 6.5-year follow
      up, metastasis of the left lobe of thyroid and right upper lobe of lung in twice
      have been sequentially detected and resected, and now she has been healthy with
      no known recurrence of the tumor. The recurrence of a non-invasive cervical
      ectopic thymoma has been reported as extremely rare, and this case indicates that
      the surgical control for recurrence lesion of cervical ectopic thymoma is
      effective when the tumor is resectable.

PMID- 19588836
TI  - [The twenty-second reports of the study on Yusho--PCBs and dioxin-related
      compounds. Foreword].

PMID- 19588837
TI  - [An epidemiologic examination on the prevalence of the periodontal diseases and
      oral pigmentation in Yusho patients in 2008].
AB  - An epidemiologic examination was carried out to reveal the prevalence of the
      periodontal diseases and oral pigmentation in patients with Yusho in 2008. The
      results obtained were as follows. 1) Yusho patients complained of tooth pain and
      periodontal diseases such as gingival swelling, gingival bleeding, but not of
      oral pigmentation. 2) 116 patients out of 148 patients with Yusho, who were
      measured periodontal pocket depth according to Ramfjord' methods, had at least
      one tooth with periodontal pocket deeper than 3 mm. Similarly, 399 teeth out of a
      total 710 examined teeth showed a periodontal pocket with more than 3 mm in
      depth. However, it was determined that 74 teeth had a periodontal pocket deeper
      than 4 mm. 3) Oral pigmentation was observed in 91 patients out of 155 patients
      with Yusho. In this study, gingival pigmentation was most predominant among oral
      pigmentation. The prevalence of oral pigmentation in male patients seemed to be
      somewhat higher than that in female patients. In addition, the prevalence of oral
      pigmentation tended to be higher in younger patients than in elder patients.
      Pigmentation of the buccal mucosa, lip or palate, however, was observed only in
      patients beyond the age of fifty. These results indicated that PCB-related
      compounds may be responsible for the higher prevalence of both periodontal
      diseases and oral pigmentation.

PMID- 19588838
TI  - [Evaluation of dermatological symptom of Yusho patients in the annual examination
      in 2005-2007].
AB  - Yusho is recognized as a poisoning by a mixture of polychlorinated biphenyls
      (PCBs), dioxins and related compounds. We have continued a follow-up of skin
      symptoms in patients not only for supporting patients' health but also for
      understanding the possible prolonged effects of exposure to PCBs and dioxins in
      humans. We evaluated the severity grades and the skin severity scores of the
      symptoms who visited the annual examinations of Fukuoka prefecture from 2005 to
      2007. Forty years have passed since the Yusho incident, and about 70% of the
      patients currently present no skin symptoms. In contrast, in about 30% of the
      patients, characteristic skin symptoms of Yusho, such as pigmentation of skin,
      black comedones and acneform eruptions, could still be observed. We analyzed
      statistical correlations between blood levels of PCBs or dioxin and skin severity
      grades.

PMID- 19588839
TI  - [Estimation of anti-SS-A Ab and anti-SS-B Ab in the serum of Yusho victims].
AB  - Polychlorinated biphenyls (PCB) causes the release of superoxide during the
      metabolic process. Therefore, Yusho victims are thought to be exposed to
      oxidative stress caused by PCB, because high concentrations of PCB are still
      detected in the serum of Yusho victims. Furthermore, oxidative stress contributes
      to the generation of autoantibodies because of oxidative modification. In order
      to estimate the autoantibody in Yusho victims, we mesured serum levels of anti-SS
      A antibody (Ab) and anti-SS-B Ab both in certified Yusho victims and age-matched
      controls. The mean values of anti-SS-A Ab were 4.0 +/- 17.1 (Index) in certified
      Yusho victims and 0.7 +/- 0.5 (Index) in controls. And the mean values of anti-SS
      B Ab were 7.4 +/- 4.6 (Index) in certified Yusho victims and 5.6 +/- 1.7 (Index)
      in controls. Although the occurrence rates of anti-SS-A Ab and anti-SS-B Ab were
      high in Yusho victims, there were no significant difference between Yusho victims
      and controls.

PMID- 19588840
TI  - [Prevalence of atopic dermatitis and serum IgE of Yusho patients].
AB  - Dioxins may have impact on the human immunological system, which would increase
      the risk to develop allergic diseases, such as atopic dermatitis. In order to
      determine the lifetime prevalence of atopic dermatitis in Yusho patients, a
      questionnaire-based survey was conducted in 2007. Six hundred and thirty-eight
      out of 731 certified yusho patients answered the questionnaires, and the
      prevalence of atopic dermatitis in Yusho patients was 8.8%. We also measured
      serum IgE in 83 certified and 98 non-certified Yusho patients who attended an
      annual medical check-up in 2007. Mean serum levels of IgE in certified Yusho
      patients were 386.2 +/- 1128.0 IU/ml, whereas those in non-certified Yusho
      patients were 272.1 +/- 603.6 IU/ml. There was no significant difference in serum
      levels of IgE between certified and non-certified Yusho patients. In addition, no
      significant correlation was observed between serum levels of IgE and blood levels
      of dioxins in certified Yusho patients.

PMID- 19588841
TI  - [Lymphocyte subpopulations in patients with Yusho].
AB  - To investigate chronic immune effects of polychlorinated biphenyl (PCB) and
      polychlorinated dibenzofuran (PCDF), lymphocyte subpopulations in peripheral
      blood were studied in 156 patients with Yusho in 2008. Significant relationships
      between the concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in the
      blood and the absolute densities of the total lymphocyte population, or of the T
      cell subpopulation reactive with CD4 were observed, while there was no
      correlation between the blood PCB levels and the densities of total lymphocyte
      population, or CD4, CD8 or CD20 positive cells in peripheral blood. Mean absolute
      densities of total lymphocyte population and T-cell subpopulation expressing CD4
      were significantly increased in the Yusho patients with high 2,3,4,7, 8-PeCDF
      levels compared with those in the patients with low 2,3,4,7,8-PeCDF levels. We
      conclude that the increase of CD4 positive cells in patients with Yusho may be
      associated with blood 2,3,4,7,8-PeCDF levels.

PMID- 19588842
TI  - [Bone mineral density, PCB, PCQ and PCDF in Yusho].
AB  - We measured bone mineral density of the distal end of radius with dual energy X
      ray absorptiometry, serum cross-linked N-telopeptides of type I collagen, serum
      bone-specific alkaline phosphatase, serum Ca, serum P, blood PCB level, blood PCQ
      level and blood PCDF level in Yusho. As a result, the osteoporosis group (< 70%
      of the young adult mean [YAM] bone mineral density [BMD]) was observed in 7.1% of
      the studied male subjects. And, the moderate group (> or = 70% and < 80% of YAM
      BMD), 16.1%, the normal (> or = 80% of YAM BMD) group was 76.8%. Also, 42.3% of
      all female tested subjects observed in osteoporosis group. The moderate group,
      19.2%, the normal group was 38.5%. There was no difference in PCB blood level,
      PCQ, PCDF for men and women in osteoporosis group, moderate group, and in the
      normal group. Serum cross-linked N-telopeptides of type I collagen increased in
      the male osteoporosis group, but serum bone-specific alkaline phosphatase did not
      change. This study was inconclusive since the results did not determine the
      influence that PCB, PCQ, PCDF gave to bone density and bone metabolism.

PMID- 19588843
TI  - [Toxic effects of PCB/PCDF to human observed in Yusho and other poisonings].
AB  - Yusho PCB poisoning occurred in 1968, when the human environment had been
      polluted with PCBs and related compounds. The causal rice oil was contaminated
      with large amounts of PCBs and PCDFs by accidental leakage at the rice oil
      producing Kanemi Company on February 7-15, 1968. Much less concentrations of PCBs
      were identified in the rice oil produced and shipped from the Company before and
      after the critical days. Concentration trend of PCBs and TEQ in human body were
      examined for 40 years from 1968 to present. Concentrations in the blood of
      heavily exposed Yusho patients and normal Japanese were PCBs : 80 and 1.5
      microg/g-fat, and TEQ : 60 and 0.1 ng/g-fat, respectively, in 1969, and decreased
      to PCBs : 1 and 0.2 microg/g-fat, and TEQ : 0.5 and 0.02 ng/g-fat, respectively,
      in 2007. PCBs and PCDFs have been persistently retained in human body for 40
      years. Serious cases of Yusho and Yucheng having very high PCB, PCDF
      concentrations in blood have suffered from severe chloracne, pigmentation, eye
      discharge and others at the first stage and recovered very slowly with a lapse of
      several years. However, their hormone mediated signs and symptoms, such as high
      triglyceride and thyroxin levels in serum, disorder of immunoglobulin, goiter,
      decrease of sperm mobility, disorder of teeth and joints conditions, decrease of
      IQ score in children, headache and numbness, etc, are persisting for more than 30
      years. The residents in East Slovakia who have been exposed to PCBs wasted from a
      PCB factory and have about 3 times higher blood PCB concentrations than the
      controls, have suffered from disorder of FT4 and T3 levels in serum, disorder of
      thyroid grand and thymus, dental defects in enamel developmental, hearing
      impairment at low frequency tone, tendency to diabetes and others. Residents in
      the Great Lakes area, USA, whose blood PCB levels are estimated to be higher than
      other places, have shown disorder of thyroid, T4, TSH levels, endometriosis,
      joint disorder, and low IQ score in children. The levels of PCBs and PCDFs in the
      blood of Yusho patients and Controls are compared to the normal levels of
      estradiol, testosterone and thyroxin. In the blood of Yusho patients,
      concentrations of single congeners of PCB118, PCB153, PCB156 and PentaCDF are
      high enough to disturb the hormonal effects. Blood PCB concentrations in normal
      Japanese are higher than the FT3 and FT4 levels, indicating hormonal disturbance
      will be easily produced. PCBs are metabolized to produce HO-PCBs, which bind to
      TTR and retain in blood medium. Blood HO-PCB concentrations in Yusho patients and
      normal persons are higher than the FT3, FT4 levels in serum. Therefore, the
      hormonal effects of thyroxin will be disturbed in Yusho and normal persons. As HO
      PCB will be easily transferred to fetus through placenta, fetus development will
      be possible to be disturbed. In Yusho and other cases, PCBs and TEQ (PentaCDF,
      PCB118 etc) were ingested together and the strong enzyme inducers of PentaCDF and
      others have metabolized PCBs to HO-PCBs, which have retained in the blood.
      Complex reactions of PCDFs, PCBs and HO-PCBs have disturbed the hormonal effects
      and the induced symptoms and diseases would have been caused.

PMID- 19588844
TI  - Concentrations of polychlorinated biphenyls in blood collected from Yusho
      patients during medical check-ups performed from 2004 to 2007.
AB  - To elucidate the exposure levels of polychlorinated biphenyls (PCBs) for Yusho
      patients, we conducted a congener-specific analysis of polychlorinated biphenyls
      (PCBs) in blood collected from 242, 237, 300, and 96 Yusho patients during
      medical check-ups performed from 2004 to 2007, respectively, and in samples from
      74, 113, 125, and 148 Yusho-suspected persons during those same years,
      respectively, and compared the individual congener concentrations of PCBs among
      the groups of Yusho patients, Yusho-suspected persons, and normal controls with
      the concentrations previously reported. Among the 209 PCB congeners, 8 congeners
      of mono-ortho PCBs and 56 congeners of non-dioxin-like PCBs were identified in
      the blood of Yusho patients and Yusho-suspected persons. Among the PCB congeners
      measured in the present study, hexaCB-153, hexaCB-138, heptaCB-180, and heptaCB
      182/heptaCB-187 showed high ratios to total concentrations of 64 PCB congeners
      detected in the blood of Yusho patients and Yusho-suspected persons from 2004 to
      2007, and the profiles of the major congeners were the same as those obtained in
      normal controls. With respect to the minor congeners of PCBs, several differences
      were observed among the three groups. The sums of the concentrations of 64 PCB
      congeners in the blood of Yusho patients from 2004 to 2007 were 645, 760, 667,
      and 510 ng g(-1) lipid for each year, respectively, and the concentrations were
      1.5, 1.8, 1.5, and 1.2 times higher than those of normal controls for each year,
      respectively. Those of the Yusho-suspected persons were approximately 0.8, 1.1,
      0.9, and 1.0 times higher than those of normal controls for each year,
      respectively. The ratios of heptachlorinated biphenyls (heptaCBs) to the total
      concentrations of 64 PCB congeners in the blood of Yusho patients and Yusho
      suspected persons from 2004 to 2007 tended to be slightly higher than those in
      the normal controls. From the results comparing the concentrations of 64 PCB
      congeners in the blood between Yusho patients and normal controls, the
      concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB-189 for Yusho
      patients were 3.4, 3.8, 3.9, and 3.8 times, respectively, 3.9, 4.1, 3.9, and 4.4
      times, respectively, 3.6, 3.9, 5.0, and 4.1 times, respectively, and 2.3, 2.5,
      2.7, and 2.9 times higher than those of the normal controls for each year from
      2004 to 2007, respectively. These results indicated that Yusho patients still
      have higher concentrations of hexaCB-156, hexaCB-157, heptaCB-181, and heptaCB
      189 in their blood than do unaffected people, even though over 35 years have
      passed since the outbreak of Yusho. These four congeners can therefore be
      considered to be the most important congeners for evaluating the PCBs exposure of
      Yusho patients.

PMID- 19588845
TI  - [Differential correlation of medical/laboratory examinations with blood levels of
      polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8
      pentachlorodibenzofuran in Yusho patients from 2001 to 2004].
AB  - BACKGROUND: Since 1968, when the Yusho poisoning incident occurred, annual
      physical, dermatological, dental, and ophthalmological and laboratory
      examinations, collectively called Yusho health checks, have been conducted for
      Yusho patients. The Yusho incident was a health hazard caused by intake of rice
      bran oil contaminated with PCB and PeCDF; therefore, since 2001 the levels of
      dioxins such as PeCDF in the blood have been measured in applicants. Here, we
      investigated correlations among findings from various medical examinations and
      those between those findings and PeCDF, PCB, and PCQ. PATIENTS AND METHODS:
      Subjects were Yusho patients who underwent Yusho annual health checks and had
      their levels of PeCDF measured between 2001 and 2004. The results of 4 years of
      health checks of those who underwent the health checks for 2 years or longer were
      aggregated to extract representative inspection items by principal component
      analysis. We also investigated the presence or absence of correlations among
      these items and PeCDF, PCB, and PCQ levels in blood. RESULTS: Using 49 variables
      extracted by principal component analysis as objective variables, we determined
      that there were correlations between the following combinations: arthralgia, A/G
      ratio and PeCDF level, ophthalmological symptoms such as excessive eye discharge
      and PCB level, and total cholesterol, inferior gingival pigmentation and PCQ
      level.

PMID- 19588846
TI  - [Estimated half-life of penta-chlorodibenzofuran (PeCDF) and simulation of PeCDF
      excretion].
AB  - The half-life of 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) in the Yusho patients
      has been reported to be approximately seven years. In the present study, we
      estimated the half-life of PeCDF using data from the medical check-ups of more
      than 300 Yusho patients. We performed linear regression analysis with a binary
      logarithm of PeCDF blood level in Yusho patients as the dependent variable, and
      the measurement year as the independent variable. Our results showed that there
      were many patients who had shown no reduction of their blood PeCDF level for
      several years. This result contradicts the previously reported half-life period.
      Therefore, we believe that a more complicated excretion model needs to be
      established to explain the discrepancy we found. We hypothesized that there might
      be two mechanisms of PeCDF assimilation in human digestive tract. In the present
      study, we also used our hypothesis to simulate PeCDF excretion in Yusho patients.

PMID- 19588848
TI  - [Investigation of PCB pollution evaluation for Yusho victims using their
      preserved umblical cord].
AB  - PCB and dioxin-like PCB (DL-PCB) in 28 umbilical cords preserved from the time
      when 3 Yusho victims and 11 healthy subjects gave birth were examined in order to
      investigate the pollution evaluation with both the compounds in Yusho victims on
      the basis of the analytical value. As a result, in a period of 1968 to the 70s
      immediately after Yusho incident, the total concentration of the 12 DL-PCB
      isomers in both the Yusho victims s and healthy subjects was very high. After
      that, the total DL-PCB concentration decreased temporally. However, there was not
      observed a significant difference in the concentration and composition of both
      contaminants between the two groups.

PMID- 19588847
TI  - [Dioxin concentration in the preserved umbilical cord from Yusho patients].
AB  - Dioxins are known as endocrine disrupters and widespread environmental
      contaminants. They are bioaccumulated in the human body. In this study, we
      determined concentrations of dioxins (PCDD, PCDF, Non-ortho PCB and Mono-ortho
      PCB) in eighteen umbilical cords provided by twelve mothers of Yusho patients and
      twelve umbilical cords provided by ten mothers of normal controls. The average
      concentrations of PCDD, PCDF, Non-ortho PCB, Mono-ortho PCB and total dioxins
      (PCDD/ F + Dioxin-like PCB) in the umbilical cords of Yusho patients and normal
      controls were 0.55, 4.55, 0.08, 0.08 and 5.26 pg-TEQ/g, respectively, and 0.50,
      0.11, 0.03, 0.02 and 0.66 pg-TEQ/g, respectively. Total dioxins and PCDF
      concentrations in the umbilical cords of Yusho patient were about 8 and 40 times
      higher than those in the umbilical cords of normal controls, respectively. The
      average concentration of 2,3,4,7,8-PeCDF in the umbilical cords of Yusho patients
      was 10 pg/g. We couldn't detect 2,3,4,7, 8-PeCDF in the umbilical cords of normal
      controls. We suspected the 2,3,4,7,8-PeCDF concentrations in the mothers' blood
      were related to the 2,3,4,7,8-PeCDF concentrations in umbilical cords.

PMID- 19588849
TI  - [Promotive excretion of causative agents of Yusho by intake of fermented brown
      rice with Aspergillus oryze in patients with Yusho --with regard to PCDFs and
      PCDDs].
AB  - Forty years have passed since the outbreak of Kanemi rice oil poisoning, namely,
      Yusho in the western Japan. However, even now the patients with Yusho have been
      still suffering from several objective and subjective symptoms. In order to
      improve or, if possible, to cure such symptoms, the most important therapeutic
      treatment is considered to actively excrete the causative agents, that is,
      polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins
      (PCDDs) from the bodies of the patients and to reduce their body burdens. In
      rats, chlorophyll and dietary fiber have been shown to promote the fecal
      excretion of PCDFs and PCDDs and to reduce their levels in rats. In this study,
      we have examined whether such kinds of effect are also observed by fermented
      brown rice with Aspergillus oryzae (FBRA) containing 5% spirulina, which is so
      called spirulina HI*GENKI, the health food and relatively rich with chlorophyll
      and dietary fiber, in eighteen patients with Yusho. They were divided into two
      groups, namely group A, ten patients (3 males and 7 females) with the mean age of
      67.7 years old and group B, eight patients (4 males and 4 females) with the mean
      age of 64.1 years old. Respective mean concentrations of the three PCDF
      congeners, that is, 2,3,4,7,8-PenCDF, 1, 2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF in
      the blood on lipid weight basis just before initiating this study were as
      follows; group A: 413, 152 and 45.7 pg/g lipid, and group B: 151, 42.7 and 17.3
      pg/g lipid. Contamination levels of these PCDF congeners in group A were 2.6 to
      3.6 times higher than those in group B. In respective mean concentrations of
      PCDFs, PCDDs and PCDFs/DDs in both groups were as follows; group A: 228, 30.9 and
      258 pg-TEQ/g lipid, and group B: 82.4, 19.7 and 102 pg-TEQ/g lipid. Contamination
      levels of PCDFs and PCDDs were around 2 times higher in group A than in group B.
      Group A took around 7.0 g of spirulina HI*GENKI after each meal and tree times a
      day for the first one year and for the second one year, they did not take
      spirulina HI*GENKI any more. Group B took spirulina HI*GENKI with the same manner
      as the group A only for the second one year. The concentrations of PCDFs and
      PCDDs in the blood of groups A and B were also measured at the end of the first
      and second year, respectively. Assuming the body fat is also contaminated with
      PCDFs and PCDDs at their concentrations on lipid weight basis in the blood and
      the content of body fat is 20% of 60 kg body weight, we computed the average
      amounts in the net excretion of PCDFs and PCDFs/DDs from the body of the patients
      due to the intake of spirulina HI*GENKI in groups A and B. As a result, in group
      A, 85.0 and 99.6 ng-TEQ/patient, respectively were excreted from the body of the
      patients. In group B, only 38.1 nd 40.0 ng-TEQ/patient were excreted.
      Accordingly, promotive excretion of PCDFs and PCDDs from the patients with Yusho
      seemed much effective in group A, of which their concentrations in the blood were
      much higher than those of group B.

PMID- 19588850
TI  - [Metabolism of 2,2',5,5'-tetrachlorobiphenyl (CB52) by rabbit liver microsomes].
AB  - Our preceding studies have reported that 2,2',5,5'-tetrachlorobiphenyl
      (tetraCB)(CB52) is mainly metabolized to 3-hydroxy (OH)-metabolite by
      phenobarbital (PB)-inducible cytochrome P450 (P450) isoforms such as CYP2B1 and
      CYP2B18. In this study, the metabolism of CB52 by liver microsomes of untreated
      and PB-treated rabbits was investigated. Rabbit liver microsomes produced mainly
      3-OH- and 4-OH-metabolites (M-1 and M-2) at an equal extent and two other
      metabolites (M-3 and M-4) and also that phenobarbital (PB) treatment accelerated
      the formation of all these metabolites, M-3 was assumed to OH-tetraCB by GC-MS.
      Another metabolite, M-4, was determined to 3,4-diOH-CB52 by GC-MS and 1H-NMR.
      Addition of antiserum against CYP2B4, a constitutive and PB-inducible rabbit P450
      isoform, to a microsomal incubation system resulted in almost complete inhibition
      of the formation of 3-OH-, 4-OH- and 3,4-diOH-metabolites. These results suggest
      that CYP2B4 plays an important role in CB52 metabolism in rabbit liver.

PMID- 19588851
TI  - [The accelerated excretion of 2,3,4,7,8-pentachlorodibenzofuran by Cholebine].
AB  - While it has been reported that the blood level of dioxins and polychlorinated
      biphenyls in humans may be decreased by treatment with colestimide, the effects
      of the agent are still obscure. To address this issue, we examined the effect of
      Cholebine, a cholesterol lowering agent containing colestimide as an active
      ingredient, on the excretion of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in
      rats. In a short term study, male Wistar rats (5 weeks-old) were given chows
      including 3% Cholebine (PenCDF/Chol group) or control chows (PenCDF group) for 7
      days after administration of 14C-labeled PenCDF (0.5 mg/kg body weight, p.o.). On
      day 1, the fecal excretion of PenCDF in the PenCDF/Chol group was greater by 15%
      compared to that of the PenCDF group. Although some increases were also observed
      during day 2 and day 7, Cholebine did not exhibit any marked effect on the fecal
      excretion of PenCDF. The tissue concentrations of PenCDF at day 7 in the
      PenCDF/Chol group showed a 20%-30% decrease compared with those of the PenCDF
      group, except that the level in the brain was comparable between the two groups.
      The fecal excretion of PenCDF in a long term study (Cholebine treatment for 28
      days) demonstrated the same tendency as that of short-term study. However, in
      long-term study, the Cholebine had no effect on the tissue concentration of
      PenCDF except for brain. An increase in PenCDF excretion by Cholebine seems to be
      due to the binding of Cholebine to bile acids as lipid carriers. This is because
      no binding of Cholebine to 14C-PenCDF was detected. These results suggest that
      Cholebine has little effect on the reabsorption of dioxin, whereas it reduces
      substantially the first absorption of dioxin.

PMID- 19588852
TI  - [Generation-to-generation TB transmission in Aichi, Central Japan -- an
      epidemiological study of 701 TB patients in 290 clusters].
AB  - OBJECTIVES: To elucidate characteristics in generation-to-generation TB
      transmission from smear positive pulmonary TB patients. SUBJECTS AND METHODS: The
      subjects of this retrospective study were 10,088 TB patients registered in Aichi
      prefecture between 1989 and 2003. Smear-positive pulmonary TB was found in 3,332.
      All registration files were reviewed to identify epidemiological links of
      patients. When linked patients with an interval of the dates of registration of
      less than 10 years were found, the first case was considered as the index case,
      and the other patients were regarded as secondary patients. All patients were
      subdivided by every 10 years of age as a generation. All patients were also
      grouped as young generations aged 0 to 29, middle-aged generations aged 30 to 59,
      and elder generations aged 60 to 99. A young generations rate (YGR) for a
      generation of index cases was defined as following; YGR=NY/NA, where NA: Number
      of whole TB secondary patients transmitted from all index cases belonging to
      generation A, and NY: Number of secondary patients aged 0-29 in NA. A same
      generation rate (SGR) for a generation of index cases was defined as following;
      SGR=NS/NA, where NA: Number of whole TB secondary patients transmitted from all
      index cases belonging to generation A, and NS: Number of secondary patients
      belonging to the same generation A in NA. RESULTS: A total of 290 clusters were
      found with 290 index cases and 411 secondary cases. Of the 290 index cases, the
      biggest number of patients was 58 for the forties, followed by 43 patients for
      the twenties and the fifties. Of the 411 secondary patients, the biggest number
      of patients was 91 for the twenties, followed by 58 patients for the thirties,
      and 158 patients or 38.4% belonged to the young generations. High YGRs were found
      in the young and middle-aged generations ranging from 37.5% to 75.0%, while YGRs
      were low in the elder generations ranging from 15.9% to 26.7%. The difference was
      significant between the fifties and the sixties (p<0.01). The YGRs were
      calculated 57.1% for the young generations, 43.5% for the middle-aged
      generations, and 18.9% for the elder generation. The differences were significant
      between the young and the middle-aged (p<0.05), as well as between the middle
      aged and the elder (p<0.001). The biggest SGR was calculated 42.2% for the
      twenties. Low SGRs were 18.2% for the forties and 17.5% for the fifties. The
      differences were significant between the twenties and the forties (p<0.01), as
      well as between the twenties and the fifties (p<0.01). The secondary patients
      aged 0 to 29 were counted 158: 123 were transmitted through intra-familial
      infection and 35 were through extra-familial infection. The major index case
      generation was the middle-aged generations with 82 or 66.7% secondary patients in
      the case of intra-familial infection, while it was the young generations with 20
      or 57.1% patients in the case of extra-familial infection. CONCLUSION: These
      findings suggest that the major sources of TB transmission to young people are
      smear-positive pulmonary TB patients aged 0 to 59.

PMID- 19588853
TI  - [Case of pulmonary tuberculosis with miliary granules, mediastinal lymph node
      enlargement and elevation of soluble interleukin-2 receptor].
AB  - An 80-year-old woman suffered from fever and loss of appetite. Her chest X-ray
      showed mediastinal tumors and diffuse granular shadows in the bilateral lung
      fields. Elevations of sIL-2r and M-protein were present. HRCT showed numerous
      small granules in both lungs and mediastinal lymph node enlargement. Tuberculosis
      DNA was detected by PCR in her sputum. Later, Mycobacterium tuberculosis was
      cultured from her sputum. After she started anti-tuberculosis therapy, her
      general fatigue and elevation of sIL-2r improved gradually. Her chest X-ray
      revealed a decrease in the size of mediastinal lymph nodes and small granules.

PMID- 19588854
TI  - [Evaluation of tuberculosis contact investigation & examination in congregate
      settings in Osaka City].
AB  - OBJECTIVE: To evaluate tuberculosis index case, group contact investigation and
      usefulness of tuberculin skin test (TST) results. METHODS: We analyzed data for
      833 groups examined by contact investigation registered in 2003-2005 in 24 wards
      of Osaka City characteristics of their index cases, TST results, and follow-up
      outcome of radiograph screening up to 2 years. RESULTS: 71.3% (7406/10378) of
      contacts completed 2 years follow-up radiograph screening. There were 54
      secondary cases. Characteristics of 38 index cases of contact groups were
      compared by the rate of causing secondary cases. Results showed that the
      following characteristics were statistically significant in causing secondary
      cases: sex (male: 5.6%, female: 1.8%, chi2 test; p<0.05), age (49 or less: 6.8%,
      50-64: 5.7%, 65 or over: 0, p<0.01), chest radiography (cavitary: 6.0%, non
      cavitary: 2.0%, p<0.05), initial AFB smear grade (G5 or over: 6.5%, G4 or less:
      2.2%, p<0.01), cough duration (2 months or more: 7.0%, less than 2 months: 2.8%,
      p<0.01), transmission risk index (10 or over: 8.4%, 0.1-9.9: 3.4%, 0: 0,
      p<0.001). As initial part of contact investigation, decision was made for each
      group whether TB secondary transmission was "likely" or "unlikely". If it was
      considered as "likely", TST was conducted for contacts. Incidence rate of
      secondary case was 0.44% in groups TST was conducted, and 0.09% in groups TST was
      not conducted. The difference was statistically significant (p<0.05). According
      to tuberculin results, 760 persons in 215 groups were given LTBI treatment.
      Comparing the number of secondary cases in the age group of 10-39 eligible for
      LTBI treatment, 19 secondary cases were detected immediately or 2 months after
      the initial contact examination, and it was reduced to 7 cases after 6 months to
      2 years. However in the age group of 40 and over not eligible of LTBI treatment,
      the number of secondary cases increased from 10 immediately or 2 months after the
      initial contact examination to 18 after 6 months to 2 years, and the difference
      was statistically significant (p< 0.01). CONCLUSION: Results of contact
      investigation and successive LTBI treatment showed that the prevention of
      secondary cases was effective, despite of some over-diagnosis of LTBI by TST.

PMID- 19588855
TI  - [Tuberculosis primary infection].
AB  - Since the introduction of mass BCG vaccination program, it has become difficult
      to know how TB primary infection takes place. Based on data before the
      introduction of mass BCG vaccination, the author tried to overview TB primary
      infection. Most TB primary infection takes place via lung as shown in Table 1.
      Soon after TB primary infection, primary focus in the lung and regional glandular
      changes were formed, and they were named primary complex, which is the
      morphological sign of TB primary infection. Comparing the location of primary
      focus in right and left lung, it was 56.6% vs. 43.4%, which just correspond to
      the right and left lung volume as shown in Table 2. Observing by the location of
      primary focus in different lung lobes, it was found more frequently in upper lobe
      than in middle and lower lobe after adjustment for volume of different lung lobes
      as shown in Fig. 1 and Table 2, however, chronic pulmonary TB is found much more
      frequently in apex or upper part of the lung. The number of primary foci was 1 in
      the majority of cases, however, 2 or more foci were found in some cases. Several
      weeks after TB primary infection, TB immunity started to work, and primary focus
      be never formed thereafter. The fact indicates that multiple primary foci were
      seen only repeated TB infection taking place in short period soon after primary
      infection. The distribution of number of primary foci should follow Poisson's
      distribution if repeated infection takes place by chance, and it should follow
      Polya-Eggenberger's distribution if chance of repeated infection takes place
      cumulatively, and observed figure matched with the latter as shown in Fig. 2.
      Location of primary complex is useful sign to determine invasion place of
      tubercle bacilli in epidemiological survey of TB infection in medical accident
      cases. If major pulmonary lesions are found in middle or lower part of lung, we
      have to suspect onset of TB soon after primary infection among immunity
      attenuated cases such as HIV/AIDS, diabetics and cases using steroid, and if
      cavities are found more likely diabetes is suspected, and no cavity with or
      without adenopathy more likely HIV/AIDS.

PMID- 19588856
TI  - The Patients' Charter for Tuberculosis Care -- patients' rights and
      responsibilities.

PMID- 19588857
TI  - A cross-sectional study of factors associated with intentions to leave among
      newly graduated nurses in eight advanced treatment hospitals: job stressors, job
      readiness, and subjective health status.
AB  - OBJECTIVES: This study was performed to examine job stressors, job readiness, and
      subjective health status as factors associated with intentions to leave among
      newly graduated nurses (NGNs) in advanced treatment hospitals in Japan. METHODS:
      From June to August 2007, anonymous self-administered questionnaires were
      distributed to all NGNs in nine advanced treatment hospitals. The questionnaire
      items addressed individual attributes, employment characteristics, organizational
      characteristics, the 22-item Job Content Questionnaire, a novel job readiness
      scale, and scales for subjective health status (cumulative fatigue and
      psychological distress) and intentions to leave. The response rate was 73%
      (n=414), and 377 completed questionnaire data sets from eight hospitals were
      analyzed. A hierarchical multiple regression analysis was performed to
      investigate the factors associated with intentions to leave and subjective health
      status. RESULTS: The results of hierarchical multiple regression analysis showed
      55% of the variance in intentions to leave. "orientation as nurse", subjective
      health status influenced by psychological job demand, and "supervisor support"
      were important independent factors of intentions to leave. Psychological job
      demand and job readiness were also important factors of subjective health status.
      CONCLUSION: To intervene in early resignation of NGNs, job stressors should be
      minimized to improve subjective health status; while simultaneously raising job
      readiness.

PMID- 19588858
TI  - [The positive psychological impact of rich childbirth experiences on child
      rearing].
AB  - OBJECTIVE: The purpose of this study was to investigate the psychological
      implications of emotionally enriching childbirth experiences for problems such as
      awareness of motherhood, postnatal depression, and parenting stress among women
      after childbirth. METHOD: All women who gave birth at five study centers (four
      birthing homes and one maternity hospital) during May 2002 and August 2003 were
      asked to participate in the cohort study. All 2314 women were approached and 1004
      eligible women agreed to take part. Analyses were conducted using a baseline
      survey and four follow-up surveys conducted at 4 months, 9 months, 2 and a half
      years, and 3 years after childbirth. The questionnaire included four scales to
      evaluate the subjects' childbirth experiences, awareness of motherhood, postnatal
      depression, and parenting stress and difficulties. Data were collected via
      structured interviews and transcription from medical records. RESULTS: Bivariate
      and multivariate analysis indicated that women who had good childbirth
      experiences had positive feelings concerning motherhood and parenting stress and
      anxiety were lower. Bivariate analysis also indicated that childbirth experience
      had an inverse relationship with postnatal depression. CONCLUSIONS: This study
      revealed that having good childbirth experiences inhibits negative awareness of
      motherhood and abusive behavior towards children. These results show that it is
      important for mothers to be provided with appropriate care during pregnancy and
      labor for preventing child abuse and parenting stress and anxiety. More research
      is needed to identify the determinants of childbirth

PMID- 19588859
TI  - [An analysis of fall accidents using Kochi Fire Department ambulance statistics].
AB  - PURPOSE: The aim of this study was to examine ambulance usage due to fall
      accidents in Kochi City. METHOD: The survey period was one year, from January to
      December, 2005. A total of 967 ambulance responses to fall accidents were
      recorded by the Kochi Fire Department during this period. Ambulance responses to
      fall accidents were analyzed in terms of sex, age, time, and place of fall.
      Adults were defined as subjects between the ages of 18 and 64; elderly adults
      were defined as being 65 or older. RESULTS: The number of ambulance responses per
      a population sample of 1000 people was 1.32 cases in adults (men 1.55, women
      1.11) and 10.48 cases in elderly adults (men 9.14, women 11.32). The proportion
      of outdoor falls for adults was 60.8%, for women and 56.8% for men. The
      respective values for elderly adults were 54.9% and 36.6%. The majority of
      elderly adult women fell down indoors. More falls occurred in winter (from
      December to February) than in the other seasons. There were more falls in
      December than other months. CONCLUSION: Fall incidence varies according to sex,
      age and season. We can conclude that the causes and places of falls are related
      to physical activity and season. Fire department ambulance records can be
      utilized to analyze fall situation in local areas. Such analyses should lead to
      new approaches to fall prevention measures.

PMID- 19588860
TI  - [Change of lower urinary tract symptoms during pregnancy and after delivery-
      investigations using IPSS/QOL and Urinary Incontinence Questionnaires].
AB  - Using International Prostate Symptom Score (IPSS)/Quality of life (QOL) and
      Urinary Incontinence Questionnaires, we collected a total of 89 questionnaires
      from 48 pregnant women (average age of 31.4 +/- 3.42) and data 4 times during
      each pregnancy (during the 14th, 26th and 36th weeks of pregnancy) and 1 month
      after delivery. We examined whether there was a relationship between the number
      of incontinence incidences listed in the questionnaires and other parameters: the
      body mass index (BMI), previous deliveries, the weight of the baby delivered, the
      use of episiotomy, etc. The average IPSS score was 5.84 +/- 4.65, 5.33 +/- 2.73,
      7.35 +/- 4.51 for the 14, 26 and 36th week, respectively and 1.82 +/- 1.76 one
      month after delivery. The major symptom reported was storage symptom and the
      scores increased as the pregnancy progressed and recovered by one month after
      delivery. The average score on the Urinary Incontinence Questionnaires was 3.32
      +/- 2.69, 5.05 +/- 3.02, 6.15 +/- 2.89 for the 14, 26 and 36th week, respectively
      and 1.59 +/- 2.03 one month after delivery. The major symptom reported was stress
      incontinence. The scores increased significantly as the pregnancy progressed and,
      one month after delivery, returned to the level at the 14th week of pregnancy. We
      found a positive correlation between the number of incidences of incontinence at
      the 36th week and the subject's BMI. Among the lower urinary tract symptoms,
      storage symptom and stress incontinence were found in the early stage of
      pregnancy. Storage symptom disappeared after delivery, but stress incontinence
      was reduced only to the level in the early stage of pregnancy.

PMID- 19588861
TI  - [A case of retroperitoneal neurofibroma successfully resected laparoscopically].
AB  - A 30-year-old woman, who had a type I neurofibromatosis, visited our hospital
      with a complaint of left flank pain. Computed tomography revealed a heterogenous
      solid mass, 12 x 7 x 6 cm in diameter, in the anterior renal region, which was
      suspected to be a benign retroperitoneal tumor. We performed laparoscopic
      resection of the tumor because of persisting left flank pain. Pathological
      diagnosis of the surgical specimen was neurofibroma. The postoperative course was
      uneventful. The diagnosis and laparoscopic management of retroperitoneal
      neurofibroma are discussed.

PMID- 19588862
TI  - [Two cases of unilateral adrenalectomy for bilateral adrenal Cushing syndrome].
AB  - For treatment of bilateral adrenal Cushing syndrome (CS) unilateral adrenalectomy
      (UAdx) is less invasive than bilateral adrenalectomy and lifetime replacement of
      glucocorticoids can be avoided. Laparoscopic UAdxs was performed on 2 patients
      with bilateral adrenal CS. In both cases, symptoms associated with CS were
      improved after UAdx. Although serum adrenocorticotropic hormone levels remained
      lower than normal after UAdxs, cortisol levels in both serum and urine have been
      maintained within normal ranges for more than 1 year in both cases.

PMID- 19588863
TI  - [Interferon alpha and half-dose sorafenib is an effective treatment modality for
      interferon alpha-resistant metastatic renal cell carcinoma: a case report].
AB  - Metastatic renal cell carcinoma is notoriously resistant to chemotherapy and
      radiotherapy. Immunotherapy with interferon alpha is widely used for the disease,
      but its treatment effects are poor. A 69-year-old Japanese women presented with
      gross hematuria. Imaging studies revealed a left renal tumor, 12 cm in diameter,
      and multiple pulmonary and hepatic lesions. No abnormal laboratory data were
      observed other than anemia with Hb 9.2 g/dl. Performance status was 0. She
      underwent radial left nepherectomy. Pathological examination showed clear cell
      renal cell carcinoma with moderate histological differentiation (grade 2) and
      microscopic vessel invasion; pT3aN0M1 (Pul, Hep). Memorial Sloon-Kettering Cancer
      Center classification was an intermediate risk due to anemia. She received
      interferon alpha, 5 million IU three times per week, postoperatively. In three
      months, hepatic lesions rapidly progressed although there was no interval change
      of pulmonary lesions. Then, the patient received interferon alpha at the same
      dose as described above and half-dose sorafenib, 400 mg per day. Grade 2
      hypertension was under control by calcium channel blocker and the hand-foot
      syndrome was not obvious. No other grade 3/4 drug-related adverse events were
      observed. In one month after combination therapy, not only pulmonary lesions but
      also hepatic lesions were smaller. She has received this combination therapy with
      stable disease for six months. Performance status was 1 with grade 1 fatigue. The
      doses of this regimen may be tolerable, and might be an available treatment
      option for interferon alpha-resistant advanced renal cancer.

PMID- 19588864
TI  - [A case of carcinoid tumor arising from a horseshoe kidney].
AB  - Carcinoid tumor of the kidney is an extremely rare neoplasm. We report a case of
      primary carcinoid tumor arising from a horseshoe kidney in a 31-year-old man. An
      abdominal bulky mass was found at a local hospital and he was referred to our
      hospital for examination and treatment. From the results of computed tomography,
      magnetic resonance imaging and angiography, we suspected renal tumor arising from
      a horseshoe kidney and performed left partial nephrectomy with isthmectomy.
      Pathological findings of hematoxylin eosin staining revealed tumor cells
      proliferating in a cord-like and ribbon-like structure and the tumor cells
      stained strongly for chromogranin A, grimelius and neuron specific enolase.
      According to these findings, we diagnosed carcinoid tumor arising from a
      horseshoe kidney.

PMID- 19588865
TI  - [A case of domestic violence-related Page kidney].
AB  - Page kidney is caused by the accumulation of blood in the perinephric or
      subcapsular space, resulting in compression of the involved kidney, renal
      ischemia and high renin hypertension. We describe a case of domestic violence
      related Page kidney. This report also reviews previously described cases of Page
      kidney.

PMID- 19588866
TI  - [Bilateral giant renal angiomyolipoma following hemodialysis in a patient with
      tuberous sclerosis].
AB  - A 49-year-old woman with tuberous sclerosis visited our hospital complaining of
      left abdominal pain. She had been diagnosed with bilateral renal angiomyolipoma
      (AML) when she was 32 years old and had been on maintenance hemodialysis since
      the age of 44. Magnetic resonance imaging showed bilateral giant renal AML and
      hemorrhage in the AML of the left kidney. Transthoracolumbar left nephrectomy was
      performed in March 2008. The resected specimen weighed 3.2 kg. The histological
      diagnosis was consistent with AML. In addition, the Japanese literature on giant
      renal AML was reviewed and discussed.

PMID- 19588868
TI  - [A case report: recurrence of urothelial cancer in an ileal conduit].
AB  - A 48-year-old man presented complaining of lower abdominal pain, and was
      diagnosed with invasive bladder cancer. After neoadjuvant chemotherapy,
      cystoprostatourethrectomy and ileal conduit diversion were performed. At 53 years
      of age, bladder cancer recurred in the upper urinary tract and he underwent
      complete urinary tract extirpation. Histological examination revealed an
      urothelial carcinoma in an ileal conduit. Three years later, a local recurrence
      led to combined modality therapy including chemotherapy and radiotherapy. He is
      receiving maintenance chemotherapy for metastatic tumors. Urothelial carcinoma
      arising in an ileal conduit after radical cystectomy for bladder cancer is
      infrequently reported. To our knowledge, only 12 cases, including ours, have been
      reported.

PMID- 19588867
TI  - [A case of upper urinary tract metastases from sigmoid colon cancer].
AB  - We report a case of colorectal cancer with metastasis to the upper urinary tract.
      A 56-year-old man had left flank pain. Ultrasonography and computed tomographic
      (CT) examination demonstrated left hydronephroureter and a soft-tissue structure
      within the left ureter. Urinary cytology of the left ureter showed class IIIb. We
      diagnosed him with ureteral cancer and performed left nephroureterectomy.
      Microscopic examination demonstrated adenocarcinoma located in ureteral and
      pelvic wall, especially in blood vessels, with intact mucosa and similar to
      adenocarcinoma of colon cancer. Therefore metastatic upper urinary tract tumor
      was suspected. Barium enema and positron emission tomography-CT demonstrated
      sigmoid colon cancer. Biopsy specimen of colon cancer demonstrated
      adenocarcinoma, which was consistent with the ureteral tumor. Finally we
      diagnosed him with metastatic upper urinary tract tumor of sigmoid colon cancer.

PMID- 19588869
TI  - [Bladder stones caused by spontaneous migration of surgical staples after cloacal
      repair: a case report].
AB  - An 11-year-old female consulted our department with complaints of urinary
      incontinence and pyuria. She had had a cloacal repair 7 years ago. The radiograph
      showed four stones in the pelvis. Magnetic resonance imaging showed two
      diverticula next to the urethra and several low intensity masses in one
      diverticulum were regarded as stones. Voiding cystourethrography showed normal
      urinary bladder contraction, although there were residual urine in the
      diverticula. Preoperatively, these stones were thought to be formed as a result
      of the long-standing residual urine. Cystourethroscopy showed that the two
      diverticula existed within the proximal area of the urethral sphincter and four
      white stones were found in them. Transurethral cystolithotripsy was performed and
      a surgical staple was found in the core of each stone. The surgical staples had
      been used for the cloacal repair and they had migrated into the bladder resulted
      in stone formation. To the best of our knowledge, this is the first report of
      bladder stones caused by the migration of surgical staples into the bladder after
      cloacal repair.

PMID- 19588870
TI  - [Eosinophilic cystitis caused by Seijo-bohhu-tou: a case report].
AB  - A 19-year-old woman was admitted to our hospital with a complaint of residual
      feeling, frequency and pain on urination. Laboratory analysis revealed an
      elevated eosinophilia count in peripheral blood and white blood cell count in
      urine. Lymphocyte stimulation test of Chinese herb named "Seijoh-bohhuh-toh"
      showed a positive reaction. Bladder symptoms were improved after ceasing this
      Chinese herb. From these points, we considered that the Chinese herb might have
      caused eosinophilic cystitis. We report this rare case with a review of the
      literature.

PMID- 19588871
TI  - [A patient with a primary malignant lymphoma surrounding the female urethra].
AB  - A 90-year-old female patient presented with dysuria. She was treated with partial
      excision of the mass protruding from the urethral meatus. Pathological
      examination revealed non-Hodgkin's malignant lymphoma of the B-cell type. The
      patient received a total of 42.4 Gy extrabeam irradiation. Our patient was
      disease-free for 14 months. We reviewed 25 cases of this rare entity reported
      previously.

PMID- 19588872
TI  - [Carcinomatous meningitis from prostate cancer diagnosed by cerebrospinal fluid
      cytology and magnetic resonance image: a case report and review of the
      literature].
AB  - A 55-year-old man was treated with 10 courses of intermittent Paclitaxel,
      estramustine phosphate sodium and carboplatin (PEC) chemotherapy for hormone
      refractory prostate cancer. He was admitted to our department with a complaint of
      severe headache 2 years after initiating chemotherapy. Enhanced computed
      tomography (CT) of the brain demonstrated no obvious lesion, but a brain dynamic
      magnetic resonance image (MRI) showed a diffusely enhanced lesion on the surface
      of the brain. Cerebrospinal fluid cytology revealed adenocarcinoma cells; and
      therefore it was diagnosed as carcinomatous meningitis metastasized from prostate
      cancer. After glycerin and betamethasone were used to control brain edema, the
      patient's headache temporarily improved. However, he died on the 36th day after
      admission in the natural course of the disease after he and his family selected
      not to undertake further active treatment. To our knowledge, only 6 cases of
      carcinomatous meningitis associated with prostate cancer have been reported in
      Japan. It is generally difficult to diagnose carcinomatous meningitis because the
      symptoms vary considerably. Once diagnosed, active treatment is not undertaken in
      most cases since the patient cannot tolerate further treatment. The prognoses for
      patients with advanced prostate cancer and metastatic carcinomatous meningitis
      are generally quite poor. Early diagnosis and prompt initiation of therapy could
      improve the quality of life for such patients. In this case study, MRI was
      superior to CT for imaging a metastatic carcinomatous meningitis lesion.

PMID- 19588873
TI  - [Infantile testicular tumor (yolk sac tumor): a case report].
AB  - A 5-month-old-male was brought to our hospital in April 2004 with left scrotal
      swelling. His serum alpha-fetoprotein AFP and human chorionic gonadotropin-beta
      levels were 6,862.9 and < 0.1 ng/ml, respectively. Computed tomography (CT)
      revealed no metastasis. Left high ligation of testis was performed. Pathological
      examination demonstrated Yolk sac tumor. He is alive without evidence of
      recurrence for 53 months postoperatively.

PMID- 19588874
TI  - [Tumor thrombus arising from the superior vena cava and extending into the right
      atrium in a patient with advanced testicular germ cell tumor].
AB  - A 24-year-old man was referred to our hospital with a painless mass on the left
      side of his neck. Ultrasonography detected right testicular tumor and
      computerized tomography scanning revealed a left supraclavicular lymph node mass
      and bulky retroperitoneal lymph node mass. He initially underwent right high
      orchiectomy, combination chemotherapy and retroperitoneal lymph node dissection
      for advanced testicular non-seminomatous germ cell tumor. Six years later, late
      relapse was detected in the lung. After complete remission of the lung metastasis
      with chemotherapy, the serum alpha-fetoprotein began to increase because of
      superior vena caval thrombus extending into the right atrium. Emergency surgical
      excision was performed successfully using extracorporeal circulation to prevent
      pulmonary embolism and the resected specimen pathologically revealed
      adenocarcinoma interpreted as teratoma malignant transformation. Adjuvant
      chemotherapy consisting of paclitaxel, ifosfamide and nedaplatin were
      administered for subsequent slight elevation of serum F-human chorionic
      gonadotropin beta, resulting in successful normalization again. Later, he
      suddenly died of cerebral infarction without any evidence of recurrence 138
      months after his initial presentation. We report herein an extremely uncommon
      case of advanced testicular germ cell tumor with development of superior vena
      caval thrombus extending into the right atrium.

PMID- 19588876
TI  - [Regulation of the miRNA function by RNA editing].

PMID- 19588875
TI  - [Ejaculatory disorder caused by doxazosin administration for blood pressure
      control in patient with pheochomocytoma].
AB  - A 29-year-old man had been treated for hypertension for 10 years. He suffered
      from speech disturbance caused by cerebral infarction, and further examinations
      were performed. Computerized tomography scan and magnetic resonance imaging
      revealed a left adrenal tumor 6 cm in size. The radioisotope (MIBG) accumulated
      in the left adrenal gland. The serum noradrenalin levels were high. Thus, the
      diagnosis of pheochomocytoma in left adrenal tumor was made. He noticed
      ejaculation disturbance 5 days after starting administration of doxazosin at the
      dose of 3 mg/day for pre-operative blood pressure control. Sperm was observed in
      the urine sampling obtained after masturbation, thus his ejaculation disturbance
      was considered to be retrograde ejaculation. Laparoscopic left adrenalectomy was
      performed. After the operation, his blood pressure normalized and the
      administration of doxazosin has not been necessary. He could perform ejaculation
      without any trouble after stopping doxazosin intake. The bladder neck conditions
      measured by ultrasonography were the same before and after the administration of
      doxazosin. The present case is a very rare case of ejaculation disturbance caused
      by non-selective alpha 1 blocker doxazosin.

PMID- 19588877
TI  - [pH homeostasis of acidic organelles].

PMID- 19588878
TI  - [Diverse physiological functions of the septin system: the protean cytoskeleton].

PMID- 19588879
TI  - [X-ray structure of vault: the largest ribonucleoprotein complex].

PMID- 19588880
TI  - [Extracellular matrix protein, Pikachurin, is required for photoreceptor ribbon
      synapse formation].

PMID- 19588881
TI  - [Human protein factory: an infrastructure to convert the human transcriptome into
      the in vitro-expressed proteome of versatile utility].

PMID- 19588882
TI  - [Recognition mechanism for poly-cyclic ether toxin by anti-ciguatoxin antibody].

PMID- 19588883
TI  - [Discovery of D-serine dehydratase in vertebrate and its deficiency in mammals].

PMID- 19588884
TI  - [Carotenoid-derived new plant hormone that regulates shoot branching].

PMID- 19588885
TI  - [Validation of small-molecule/protein interactions by the T7 phage display
      strategy using a quartz-crystal microbalance device].

PMID- 19588886
TI  - [Cell function analysis by fluorescence fluctuation spectroscopy].

PMID- 19588887
TI  - Scanning microbeam small-angle X-ray diffraction study of interfacial
      heterogeneous crystallization of fat crystals in oil-in-water emulsion droplets.
AB  - We performed scanning microbeam small-angle X-ray diffraction (micro-SAXD)
      experiments, differential scanning calorimetry (DSC) analysis, and optical
      microscopic observation of palm mid fraction (PMF) crystals in oil-in-water
      emulsion droplets. The scanning micro-SAXD experiment was performed by
      irradiating a synchrotron radiation X-ray microbeam having an area of 5 x 5
      microm(2) onto different positions on a 50 microm diameter emulsion droplet after
      the crystallization of PMF by chilling the emulsion at 5 degrees C. The micro
      SAXD patterns were recorded with a two-dimensional (2D) detector, which enabled
      spatial analysis of polymorphic structures and the orientation of lamella planes
      of PMF crystals at different positions inside the emulsion droplet. Particular
      attention was paid to compare the crystallization of PMF in two types of emulsion
      droplets, hydrophilic polyoxyethylene sorbitan mono-oleate (Tween 80) alone
      (Tween 80 emulsion) and Tween 80 and hydrophobic sucrose palmitic acid oligoester
      (P-170) (Tween 80+P-170 emulsion). The DSC study revealed that the PMF
      crystallization temperature in the Tween 80+P-170 emulsion droplets increased by
      3 degrees C compared to that of the Tween 80 emulsion because of the effects of
      the P-170 additive in promoting PMF crystallization. The micro-SAXD studies
      revealed the following results. (1) The lamella planes of PMF crystals near the
      outer edges of the droplet in the Tween 80+P-170 emulsion were mostly parallel to
      an oil-water interface, whereas the lamella planes of PMF crystals were not
      always aligned with the oil-water interface in the Tween 80 emulsion droplet. (2)
      The degree of orientation of the lamellar planes of PMF crystals, which was
      evaluated from the values of full width at half-maximum of 2D micro-SAXD patterns
      with respect to azimuthal angle extension, was remarkably higher in the Tween
      80+P-170 emulsion than in the Tween 80 emulsion. (3) Polymorphic transformation
      of PMF from alpha to beta' in the Tween 80+P-170 emulsion was retarded compared
      to that in the Tween 80 emulsion. These results confirmed that the P-170 additive
      caused interfacial heterogeneous nucleation through hydrophobic interactions at
      the oil-water interfaces in the emulsion, which subsequently influenced the
      arrangements of fat crystals so that the lamellar planes of fat crystals were
      parallel to the oil-water interface.

PMID- 19588888
TI  - Fluorous TBAF: a convenient and selective reagent for fluoride-mediated
      deprotections.
AB  - A fluorous analogue of TBAF has been developed for its use in the clean removal
      of silicon-derived protecting groups. Purification of the crude mixtures by
      fluorous solid-phase extractions allowed alcohols, amines, and carboxylic acids
      to be obtained in high purity, with no need of chromatographic separations. The
      moderate reactivity of fluorous TBAF was exploited in selective deprotections of
      several bifunctional molecules.

PMID- 19588891
TI  - Accurate oxidation potentials of benzene and biphenyl derivatives via electron
      transfer equilibria and transient kinetics.
AB  - Nanosecond transient absorption methods were used to determine accurate oxidation
      potentials (E(ox)) in acetonitrile for benzene and a number of its alkyl
      substituted derivatives. E(ox) values were obtained from a combination of
      equilibrium electron-transfer measurements and electron-transfer kinetics of
      radical cations produced from pairs of benzene and biphenyl derivatives, with one
      member of the pair acting as a reference. Using a redox-ladder approach,
      thermodynamic oxidation potentials were determined for 21 benzene and biphenyl
      derivatives. Of particular interest, E(ox) values of 2.48 +/- 0.03 and 2.26 +/-
      0.02 V vs SCE were obtained for benzene and toluene, respectively. Because of a
      significant increase in solvent stabilization of the radical cations with
      decreasing alkyl substitution, the difference between ionization and oxidation
      potentials of benzene is approximately 0.5 eV larger than that of
      hexamethylbenzene. Oxidation potentials of the biphenyl derivatives show an
      excellent correlation with substituent sigma+ values, which allows E(ox)
      predictions for other biphenyl derivatives. Significant dimer radical cation
      formation was observed in several cases and equilibrium constants for
      dimerization were determined. Methodologies are described for determining
      accurate electron-transfer equilibrium constants even when dimer radical cations
      are formed. Additional equilibrium measurements in trifluoroacetic acid,
      methylene chloride, and ethyl acetate demonstrated that solvation differences can
      substantially alter and even reverse relative E(ox) values.

PMID- 19588889
TI  - Molecular structure and biochemical properties of the HCCH-Zn2+ site in HIV-1
      Vif.
AB  - Virion infectivity factor (Vif) is an HIV accessory protein that is essential for
      the infection of CD4(+) T cells. Vif recruits a Cullin 5 (Cul5)-based ubiquitin
      ligase that targets a host cytidine deaminase, apolipoprotein B mRNA editing
      enzyme catalytic polypeptide-like 3G (APOBEC3G), for proteasomal degradation. The
      Vif N-terminus binds APOBEC3G, and the C-terminus interacts with the Cul5-based
      ubiquitin ligase machinery. Within the C-terminus, a highly conserved H(108)-X(5)
      C(114)-X(17-18)-C(133)-X(3-5)-H(139) (HCCH) motif binds zinc and is implicated in
      the Vif-Cul5 interaction. We have employed the biomimetic peptide HCCHp (HIV-1
      Vif amino acids 101-142) in order to determine the zinc ligands and investigate
      the role of zinc binding in Cul5 recognition. Using CD spectroscopy, a
      competitive zinc binding assay, and a light scattering assay, we found that
      mutation of the conserved His and Cys residues in HCCHp had little effect on
      secondary structure but reduced zinc binding affinity and altered the aggregation
      properties of the peptides. X-ray absorption spectroscopy was used to study zinc
      coordination in wild-type HCCHp. The data are consistent with S(2)N(imid)(2)
      coordination and strongly suggest that His-108, Cys-114, Cys-133, and His-139 are
      zinc ligands. Mutation of one or both conserved Cys residues in HCCHp led to a
      decrease in Cys ligation, and an increase in the number of (N, O) ligands, with
      noninteger coordination numbers suggesting zinc site heterogeneity. A purified
      fragment of human Cul5 was found to inhibit zinc-induced aggregation of HCCHp,
      and pull-down experiments revealed that zinc binding to HCCHp increases the
      strength of the HCCHp-Cul5 interaction by 8-fold.

PMID- 19588893
TI  - Molecular ordering of layer-by-layer polyelectrolyte films studied by sum
      frequency vibrational spectroscopy.
AB  - The molecular arrangement in organic thin films is crucial for their increasing
      technological applications. Here, we use vibrational spectroscopy by sum
      frequency generation (SFG) to study the ordering of polyelectrolyte layers
      adsorbed on silica for all steps of layer-by-layer (LbL) self-assembly. In situ
      measurements during adsorption and rinsing showed that the adsorbed polymer has a
      disordered conformation and confirmed surface charge overcompensation upon
      polyelectrolyte adsorption by probing the interfacial electric field. In dry
      films, the polymer chains acquired a net orientational ordering, which was
      affected, however, by the adsorption of subsequent layers. Such a detailed
      characterization may allow the control of LbL film structure and functionality
      with unprecedented power.

PMID- 19588890
TI  - Association of insulin-like growth factor 2 with the insulin-linked polymorphic
      region in cultured fetal thymus cells.
AB  - The insulin-linked polymorphic region (ILPR) is a regulatory sequence in the
      promoter region upstream of the human insulin gene and is widely recognized as a
      locus of type 1 diabetes susceptibility. Polymorphism of the ILPR sequence can
      affect expression of both insulin and the adjacent insulin-like growth factor 2
      (IGF-2) gene. Several ILPR variants form G-quadruplex DNA structures in vitro
      that exhibit affinity binding to insulin and IGF-2. It has been suggested that
      the ILPR may form G-quadruplexes in vivo as well, raising the possibility that
      insulin and IGF-2 may bind to these structures in the ILPR in chromatin of live
      cells. This work establishes the presence of IGF-2 in the nucleus of cells
      cultured from human fetal thymus and its association with the ILPR in the
      chromatin of these cells. In vitro experiments support the involvement of G
      quadruplex DNA in the binding interaction.

PMID- 19588894
TI  - Size, shape, and charge of salt-free catanionic microemulsion droplets: a small
      angle neutron scattering and modeling study.
AB  - The formation and microstructure of a novel microemulsion based on a salt-free
      catanionic surfactant have been examined by considering the
      hexadecyltrimethylammonium octylsulfonate (TASo)-decane-D2O system and using
      small-angle neutron scattering and self-diffusion NMR. With focus on the
      emulsification failure boundary, o/w discrete droplets have been observed and
      characterized for all of the studied microemulsion range. The evaluation of the
      experimental data was facilitated by using structure factors of a model system
      composed of charged particles interacting with a screened Coulomb potential.
      Furthermore, a more simplified model involving a charge regulation mechanism has
      been employed. Both approaches support the view that the droplets are mainly
      spherical, fairly monodisperse, and charged. The net charge of the surfactant
      film is a consequence of the partial dissociation of the short-chain counterpart,
      owing to its higher solubility. We have further quantified how the droplet charge
      varies with volume fraction and, from that dependence, explained the unusual
      phase behavior of the TASo-water system, a seldom found coexistence of two
      lamellar liquid-crystalline phases in a binary system. This coexistence is
      quantitatively modeled in terms of a fine balance between the attractive and
      repulsive colloidal forces acting within the system.

PMID- 19588895
TI  - Electronic structure of the quinone radical anion A1*- of photosystem I
      investigated by advanced pulse EPR and ENDOR techniques.
AB  - Vitamin K1 (VK1) is an important cofactor of the electron-transfer chain in
      photosystem I (PS I), referred to as A1. The special properties of this quinone
      result from its unique interaction(s) with the protein surrounding. In
      particular, a single H-bond to neutral A1 was identified previously in the X-ray
      crystal structure of PS I. During light-induced electron transfer in PS I, A1 is
      transiently reduced to the radical anion A1*-. In this work, we characterized the
      electron spin density distribution of A1*- with the aim of understanding the
      influence of the protein surrounding on it. We studied the light-induced spin
      polarized radical pair P700*+A1*- and the photoaccumulated radical anion A1*-,
      using advanced pulse EPR, ENDOR, and TRIPLE techniques at Q-band (34 GHz).
      Exchange with fully deuterated quinone in the A1 binding site allowed
      differentiation between proton hyperfine couplings from the quinone and from the
      protein surrounding. In addition, DFT calculations on a model of the A1 site were
      performed and provided proton hyperfine couplings that were in close agreement
      with the ones determined experimentally. This combined approach allowed the
      assignment of proton hyperfine coupling tensors to molecular positions, thereby
      yielding a picture of the spin density distribution in A1*-. Comparison with VK1*
      in organic solvents (Epel et al. J. Phys. Chem. B 2006, 110, 11549.) leads to
      the conclusion that the single H-bond present in both the radical pair P700*+A1*-
      and the photoaccumulated radical anion A1*- is, indeed, the crucial factor that
      governs the electronic structure of A1*-.

PMID- 19588896
TI  - Characterization of the weak SS bonds in the OSSSO and O2SSSO2 molecules.
AB  - The weak S1-S3 bonds in the OSSSO trans-disulfoxide and the corresponding
      sulfone, O(2)SSSO(2), are readdressed at the B3LYP/6-31+G(d) level using both the
      atoms-in-molecules (AIM) and the electron localization function (ELF) approaches.
      The S1-S3 bonds are clearly characterized as fractional (i.e., with a bond number
      or bond order which is less than unity) or protocovalent and are very similar in
      nature to the weak N-N bond in O(2)NNO(2). These results are in accord with what
      is obtained by inspection of valence bond structures of the increased-valence
      type.

PMID- 19588897
TI  - Gas-phase enantioselectivity of chiral N-linked peptidoresorc[4]arene isomers
      toward dipeptides.
AB  - The gas-phase enantioselectivity of cone N-linked peptidoresorc[4]arenes
      (generally symbolized as M) toward the homologue dipeptides (generally symbolized
      as A) has been evaluated by measuring the kinetics of the A release from the
      diastereomeric [M x H x A](+) complexes induced by (R)-(-)-2-butylamine (B). In
      most cases investigated, the heterochiral [M x H x A](+) complexes, namely those
      wherein the configuration of the A guest is opposite to that of the host M
      pendants, react faster (up to 5 times) than the homochiral analogues, wherein
      guest A guest has the same configuration of the host M pendants. The kinetic
      results, discussed in the light of previous MS and NMR evidence, indicate that
      both the efficiency and the enantioselectivity of the guest exchange reaction
      depend essentially on the structure and the relative stability of the
      diastereomeric [M x H x A](+) complexes. These, in turn, depend on the functional
      groups and the configuration of both the guest and the host pendants. The absence
      of any significant effects of the B configuration indicates that, in all systems
      investigated, the dipeptide guest A is predominantly located outside the host
      chiral cavity.

PMID- 19588898
TI  - Molecules: what kind of a bag of atoms?
AB  - As discussed by Liang and Dill, Enright and Leitner, and others, proteins are not
      3D objects. We study an expanded macromolecular data set ranging from proteins to
      RNA, lipids, and viruses, and remove surface effects and size bias. Molecules and
      molecular assemblies with more than 1000 backbone atoms have a volume fractal
      dimension of D(v) = 2.70 +/- 0.05 by the embedded sphere method and D(v) = 2.71
      +/- 0.04 by the ensemble method using radius of gyration as the size measure. The
      much larger D(v) = 2.89 +/- 0.05 obtained with the average surface radius as the
      length measure shows that surface corrugation is as extensive as cavity
      formation. Using a simple "Swiss cheese" model for molecules, we show that the
      distribution of voids in the interior of molecules cannot be a Boltzmann
      distribution of void energy as a function of void size. Instead, frustration from
      imperfect packing builds up with molecular size, allowing larger voids to form in
      larger molecules. We find that large molecules lie halfway between the extremes
      of packing for homogeneous objects (D = 3) and Apollonian packing, which accounts
      for packing of a hierarchy of random-sized objects (D approximately 2.47).

PMID- 19588899
TI  - Computational studies on metathetical and redox processes of HOCl in the gas
      phase. 1. Reactions with H, O, HO, and HO2.
AB  - The potential energy surfaces of four reactions including (a) HOCl + H, (b) HOCl
      + O, (c) HOCl + HO, (d) HOCl + HO(2), have been studied by the CCSD(T)/aug-cc
      pVTZ//CCSD/aug-cc-pVDZ, CCSD(T)/aug-cc-pVTZ//CCSD/cc-pVDZ, and CCSD(T)/6
      311+G(3df,2p)//BH&HLYP/6-311+G(3df,2p) levels of theory. For both HOCl + H and
      HOCl + O, the direct Cl-abstraction channels take place via the lowest energy
      barriers; for both HOCl + HO and HOCl + HO(2), the lowest energy barrier channels
      are the indirect H-abstraction reactions by HO(x) (x = 1, 2) via long-lived
      reaction intermediates. The rate constants for the low barrier channels have been
      calculated in the temperature range 200-3000 K by statistical theory. The
      predicted rate constants for HOCl + H and HOCl + HO are in good agreement with
      experimental results whereas that for HOCl + O was found to be in disagreement
      with the majority of available experimental data, suggesting a need for further
      improvement in theory and/or experiment.

PMID- 19588900
TI  - Spin-polarized density functional theory study of reactivity of diatomic molecule
      on bimetallic system: the case of O2 dissociative adsorption on Pt monolayer on
      Fe(001).
AB  - The energetics of O(2) adsorption and dissociation are discussed in terms of 6D
      potential energy surface based on spin-polarized density functional theory
      calculations that predict O(2) access to both molecular and dissociative
      chemisorption wells with no obvious barriers. Specifically, a molecularly
      chemisorbed state in a top-bridge-top (t-b-t) configuration is identified, and a
      "no barrier" dissociative adsorption over hollow site with the O-O axis spanning
      toward the bridge sites (b-h-b) is noted. Both the translation of O(2) from the
      molecular state (t-b-t) to the dissociated state on bridge and the direct
      nonactivated dissociative adsorption over the hollow sites (b-h-b) are likely
      pathways for O(2) dissociation. Interestingly, such O(2) reaction pathways are
      consistent with the density functional theory calculations and molecular beam
      experiments on O(2) dissociative adsorption on Pt(100)-(1 x 1). Modification of
      the electronic structure of the Pt surface due to the Fe substrate relevant for
      O(2) reactivity is discussed in an effort to provide insight into the
      experimentally discovered significant enhancement in electrocatalytic activity of
      Pt-Fe alloys for fuel cell applications.

PMID- 19588902
TI  - A series of new infrared NLO semiconductors, ZnY6Si2S14, Al(x)Dy3(Si(y)Al(1
      y))S7, and Al0.33Sm3SiS7.
AB  - Four new quaternary isostructural rare-earth thiosilicates, ZnY(6)Si(2)S(14) (1),
      Al(0.50)Dy(3)(Si(0.50)Al(0.50))S(7) (2), Al(0.38)Dy(3)(Si(0.85)Al(0.15))S(7) (3),
      and Al(0.33)Sm(3)SiS(7) (4), crystallized in the chiral and polar space group
      P6(3), have been prepared by a facile synthetic routine. Compounds 1-3 show
      strong second harmonic generation effects at 2.1 um with the intensities of 1, 2,
      and 3 being about 2, 2, and 1 times that of KTP (KTiOPO(4)), respectively. The
      calculated band structure of 1 implies that the optical absorptions of
      BLn(6)M(2)Q(14) and ALn(3)MQ(7) family compounds are mainly ascribed to the
      charge transitions from Q-p to Ln-4f (4d for Y) states. Compounds 2-4 exhibit
      antiferromagnetic-like interactions.

PMID- 19588901
TI  - The flexibility of a distant loop modulates active site motion and product
      release in ribonuclease A.
AB  - The role of the flexible loop 1 in protein conformational motion and in the
      dissociation of enzymatic product from ribonuclease A (RNase A) was investigated
      by creation of a chimeric enzyme in which a 6-residue loop 1 from the RNase A
      homologue, eosinophil cationic protein (ECP), replaced the 12-residue loop 1 in
      RNase A. The chimera (RNase A(ECP)) experiences only local perturbations in NMR
      backbone chemical shifts compared to WT RNase A. Many of the flexible residues
      that were previously identified in WT as involved in an important conformational
      change now experience no NMR-detected millisecond motions in the chimera.
      Likewise, binding of the product analogue, 3'-CMP, to RNase A(ECP) results in
      only minor chemical shift changes in the enzyme similar to what is observed for
      the H48A mutant of RNase A and in contrast to WT enzyme. For both RNase A(ECP)
      and H48A there is a 10-fold decrease in the product release rate constant,
      k(off), compared to WT, in agreement with previous studies indicating the
      importance of flexibility in RNase A in the overall rate-limiting product release
      step. Together, these NMR and biochemical experiments provide additional insight
      into the mechanism of millisecond motions in the RNase A catalytic cycle.

PMID- 19588903
TI  - Substitution effect on the cylization/fluorination reaction of N-dienes in
      superacid.
AB  - The novel cyclization/fluorination reaction of N-dienes in superacid was extended
      to substituted substrates. The influence of the substitution on
      superelectrophilic character of dicationic intermediates was shown and its
      dramatic effect on the synthesis of fluoropiperidines was studied. On the basis
      of new dicationic alpha-chloronium ammonium intermediates, starting from halogen
      substituted dienes, high-valued fluorinated piperidines were synthesized.

PMID- 19588904
TI  - Isotope-selective detection and imaging of organic nanolayers.
AB  - Magnetic resonance force microscopy (MRFM) makes use of the spectroscopic nature
      of magnetic resonance to add unambiguous elemental selectivity to scanning probe
      microscopy. We show isotopic selectivity of MRFM for three nuclei, (1)H, (31)P,
      and (13)C, in organic materials. We also detect a roughly 1 nm thick layer of
      naturally occurring adsorbates on a gold surface by measuring the magnetic
      resonance signal of the hydrogen contained in the layer. Finally, we detect the
      signal from hydrogen present on a carbon nanotube and use it to perform a three
      dimensional magnetic resonance image of the 10 nm diameter object.

PMID- 19588905
TI  - Analytic model for diffuse reflectivity of silicon nanowire mats.
AB  - Disordered silicon nanowires are diffuse optical reflectors, with reflectivity
      modified by the nanowire absorption. We present an analytical model which
      describes the reflectivity, absorption, and transmission of a nanowire mat,
      across a wide spectral range, and including substrate effects. The model provides
      the ability to predict the optical properties of other nanowire mat structures,
      including core/shell heterostructures.

PMID- 19588906
TI  - Direct growth of compound semiconductor nanowires by on-film formation of
      nanowires: bismuth telluride.
AB  - Bismuth telluride (Bi(2)Te(3)) nanowires are of great interest as nanoscale
      building blocks for high-efficiency thermoelectric devices. Their low-dimensional
      character leads to an enhanced figure-of-merit (ZT), an indicator of
      thermoelectric efficiency. Herein, we report the invention of a direct growth
      method termed On-Film Formation of Nanowires (OFF-ON) for making high-quality
      single-crystal compound semiconductor nanowires, that is, Bi(2)Te(3), without the
      use of conventional templates, catalysts, or starting materials. We have used the
      OFF-ON technique to grow single crystal compound semiconductor Bi(2)Te(3)
      nanowires from sputtered BiTe films after thermal annealing at 350 degrees C. The
      mechanism for wire growth is stress-induced mass flow along grain boundaries in
      the polycrystalline film. OFF-ON is a simple but powerful method for growing
      perfect single-crystal compound semiconductor nanowires of high aspect ratio with
      high crystallinity that distinguishes it from other competitive growth approaches
      that have been developed to date.

PMID- 19588907
TI  - Surface-modified nanotube anodes for high performance organic light-emitting
      diode.
AB  - In this work, we reported high performance OLED devices with transparent and
      conductive carbon nanotube anodes after modification. The modifications include
      IMRE proprietary PEDOT:PSS composite top coating (PS(C)), concentrated HNO(3)
      acid soaking, and polymer encapsulation. For PS(C)-modified nanotube thin film
      anode, we achieved maximum luminescence of approximately 9000 cd/m(2), close to
      ITO-based OLED device performance, and high efficiency of approximately 10 cd/A,
      similar with ITO-based OLED device. The performance is approximately 30 to 450
      times better than that achieved for OLED devices using CNT anodes by others. In
      addition, we also investigate the mechanical property, work function, sheet
      resistance, and surface morphology of modified carbon nanotube thin-film anodes.

PMID- 19588908
TI  - Diverse alkanones by catalytic carbon insertion into the formyl C-H bond. Concise
      access to the natural precursor of achyrofuran.
AB  - Over a century ago, the first reactions of diazomethane with aldehydes delivered
      methyl ketones. In the interim, aldehydes have been homologated with
      trimethylsilyldiazomethane, diazoacetates, and aryldiazomethanes, on rare
      occasion with catalysis. This work describes a mild procedure for convergent
      ketone assembly from nonstabilized diazoalkanes, including examples of chiral
      ketone synthesis with disubstituted (internal) nucleophiles. The method's
      remarkable tolerance to steric crowding is showcased in a simple approach to
      achyrofuran, a complex dibenzofuran.

PMID- 19588909
TI  - (PhTe)2-mediated intramolecular radical cyclization of o-ethynylaryl isocyanides
      leading to bistellurated quinolines upon visible-light irradiation.
AB  - Upon treatment with (PhTe)(2) under visible-light irradiation, o-ethynylaryl
      isocyanides underwent intramolecular radical cyclization with introduction of
      telluro groups, affording the corresponding bistellurated quinolines.

PMID- 19588910
TI  - Total synthesis of the beta-catenin inhibitor, (-)-agelastatin A: a second
      generation approach based on radical aminobromination.
AB  - The second-generation approach to (-)-agelastatin A has been established. The
      present strategy features the FeBr(2)-mediated radical cyclization of 2
      cyclopentenyloxycarbonyl azide that allows for the stereoselective installation
      of a cis-vicinal aminobromo functionality suitable for producing the BCD-ring
      system of agelastatin A. The aminobromination method streamlines access to
      oxazolidinone, a key intermediate in the previously reported synthesis, thereby
      culminating in the new total synthesis of (-)-agelastatin A.

PMID- 19588911
TI  - Dynamic kinetic asymmetric allylation of hydrazines and hydroxylamines.
AB  - Hydrazines and hydroxylamines have been found to be excellent nucleophiles for
      the palladium-catalyzed dynamic asymmetric allylic amination of vinyl epoxide,
      with good yields and enantioselectivities of up to 97% ee. This method is
      applicable to acyclic and heterocyclic amines and was applied toward a five-step
      synthesis of (R)-piperazic acid.

PMID- 19588913
TI  - Total synthesis of (-)- and (+)-tedanalactam.
AB  - The first stereoselective route providing access to both enantiomers of
      tedanalactam, a naturally occurring piperidone, has been developed. The
      stereogenic centers were generated by the use of Sharpless asymmetric
      dihydroxylation. Tandem oxidation-Wittig reaction and one-pot deprotection,
      lactamization, and oxirane ring formation are the other key elements.

PMID- 19588912
TI  - A novel beta-defensin structure: big defensin changes its N-terminal structure to
      associate with the target membrane.
AB  - Big defensin is a 79-residue peptide derived from hemocytes of the Japanese
      horseshoe crab. The amino acid sequence of big defensin is divided into an N
      terminal hydrophobic domain and a C-terminal cationic domain, which are
      responsible for antimicrobial activities against Gram-positive and -negative
      bacteria, respectively. The N-terminal domain of big defensin forms a unique
      globular conformation with two alpha-helices and a parallel beta-sheet, while the
      C-terminal domain adopts a beta-defensin-like fold. Although our previous study
      implied that big defensin changes its N-terminal structure in a micellar
      environment, due to the poor quality of the NMR spectra it remained to be
      resolved whether the N-terminal domain adopts any structure in the presence of
      micelles. In this analysis, we successfully determined the structure of the N
      terminal fragment of big defensin in a micellar solution, showing that the
      fragment peptide forms a single alpha-helix structure. Moreover, NMR experiments
      using paramagnetic probes revealed that the N-terminal domain of big defensin
      penetrates into the micelle with a dipping at the N-terminal edge of the alpha
      helix. Here, we propose a model for how big defensin associates with the target
      membrane.

PMID- 19588914
TI  - Direct asymmetric catalytic thienylaluminum addition to ketones: a concise
      approach to the synthesis of (S)-tiemonium iodide.
AB  - A direct asymmetric addition of a (2-thienyl)aluminum reagent to ketones
      catalyzed by a titanium catalyst of (S)-BINOL to afford chiral tertiary 2-thienyl
      alcohols is reported. The catalytic system works excellently for aromatic ketones
      and for 1-acetylcyclohexene, furnishing products in excellent
      enantioselectivities of up to 97% ee. However, the additions to dialkyl ketones
      afford products in low enantioselectivities of 8-17% ee. Importantly, a concise 3
      step synthesis of (S)-tiemonium iodide with an 84% yield is demonstrated.

PMID- 19588915
TI  - Two families of synthetic peptides that enhance fibrin turbidity and delay
      fibrinolysis by different mechanisms.
AB  - When fibrin clots are formed in vitro in the presence of certain positively
      charged peptides, the turbidity is enhanced and fibrinolysis is delayed. Here we
      show that these two phenomena are not always linked and that different families
      of peptides bring about the delay of lysis in different ways. In the case of
      intrinsically adhesive peptides corresponding to certain regions of the
      fibrinogen gammaC and betaC domains, even though these peptides bind to
      fibrin(ogen) and enhance turbidity, the delay in lysis is mainly due to direct
      inhibition of plasminogen activation. In contrast, for certain pentapeptides
      patterned on fibrin B knobs, the delay in lysis is a consequence of how fibrin
      units assemble. On their own, these B knob surrogates can induce the gelation of
      fibrinogen molecules. The likely cause of enhanced clot turbidity and delay in
      fibrinolysis was revealed by a crystal structure of the D-dimer from human
      fibrinogen cocrystallized with GHRPYam, the packing of which showed the direct
      involvement of the ligand tyrosines in antiparallel betaC-betaC interactions.

PMID- 19588916
TI  - Inhibitor of apoptosis (IAP) proteins: novel insights into the cancer-relevant
      targets for cell death induction.
AB  - Inhibitor of apoptosis (IAP) proteins are expressed at high levels in various
      cancers and block apoptosis at a key node. Therefore, there is currently much
      interest in IAP antagonists as cancer therapeutics. Structure-based development
      of selective IAP inhibitors now provides, for the first time, evidence that
      simultaneous inhibition of the c-IAP proteins and XIAP is necessary for efficient
      induction of cancer cell death by IAP antagonists.

PMID- 19588917
TI  - Photodissociation of 3-bromo-1,1,1-trifluoro-2-propanol at 193 nm: laser-induced
      fluorescence detection of OH(nu'' = 0, J'').
AB  - Photodissociation of 3-bromo-1,1,1-trifluoro-2-propanol (BTFP) has been
      investigated at 193 nm, employing the laser photolysis laser-induced fluorescence
      technique. The nascent OH product was detected state selectively, and the energy
      released into translation, rotation, and vibration of the photoproducts has been
      measured. OH is produced mostly vibrationally cold, with a moderate rotational
      excitation, which is characterized by a rotational temperature of 640 +/- 140 K.
      However, an appreciable amount of the available energy of 36.1 kcal mol(-1) is
      released into translation of OH (15.1 kcal mol(-1)). OH product has no preference
      for a specific spin-orbit state, Pi(3/2) or Pi(1/2). However, between two Lambda
      doublet states, Pi(+) and Pi(-), the OH product has a preference for the former
      by a factor of 2. A mechanism of OH formation from BTFP on excitation at 193 nm
      is proposed, which involves first the direct C-Br bond dissociation from a
      repulsive state (n(Br)sigma*(C-Br)) as a primary process. The primary product,
      F(3)C-CH(OH)-CH(2), with sufficient internal energy undergoes spontaneous C-OH
      bond dissociation, through a loose transition state. The formation rate of OH is
      calculated to be 5.8 x 10(6) s(-1) using Rice-Ramsperger-Kassel-Marcus
      unimolecular rate theory. Experimental results have been supported by theoretical
      calculations, and energies of various low-energy dissociation channels of the
      primary product, F(3)C-CH(OH)-CH(2), have been calculated.

PMID- 19588918
TI  - Reactivity of a thick BaO film supported on Pt(111): adsorption and reaction of
      NO2, H2O, and CO2.
AB  - Reactions of NO2, H2O, and CO2 with a thick (>20 monolayer equivalent (MLE)) BaO
      film supported on Pt(111) were studied with temperature programmed desorption
      (TPD) and X-ray photoelectron spectroscopy (XPS). NO2 reacts with a thick BaO
      layer to form surface nitrite-nitrate ion pairs at 300 K, while only nitrates
      form at 600 K. In the thermal decomposition process of nitrite-nitrate ion pairs,
      first nitrites decompose and desorb as NO. Then nitrates decompose in two steps:
      at lower temperature with the release of NO2 and at higher temperature, nitrates
      dissociate to NO+O2. The thick BaO layer converts completely to Ba(OH)2 following
      the adsorption of H2O at 300 K. Dehydration/dehydroxylation of this hydroxide
      layer can be fully achieved by annealing to 550 K. CO2 also reacts with BaO to
      form BaCO3 that completely decomposes to regenerate BaO upon annealing to 825 K.
      However, the thick BaO film cannot be converted completely to Ba(NOx)2 or BaCO3
      under the experimental conditions employed in this study.

PMID- 19588919
TI  - Enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2
      (hydroxymethyl)cyclohexylcarbamate using an iodolactamization as the key step.
AB  - An efficient enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert
      butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 2, an essential
      intermediate for a series of potent CCR2 antagonists, is described. The key step
      in the sequence is an iodolactamization to yield the highly functionalized
      (1R,2S,4S,5S)-tert-butyl 2-(benzyloxycarbonylamino)-4-iodo-7-oxo-6
      azabicyclo[3.2.1]octane-6-carboxylate 11. An examination of the reaction
      mechanism within the 2-step iodolactamization sequence led to the discovery of a
      single-pot transformation of increased efficiency.

PMID- 19588920
TI  - A general methodology toward drug/dye incorporated living copolymer-protein
      hybrids: (NIRF dye-glucose) copolymer-avidin/BSA conjugates as prototypes.
AB  - Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer
      radical polymerization (ATRP). Subsequent deprotection was performed to yield
      poly(acrylic acid) (PAA) possessing a reactive chain-end. A one-pot sequential
      amidation of the PAA with the amine derivatives of a near-infrared fluorescent
      dye (ADS832WS) and glucose produced NIRF dye-incorporated water-soluble
      copolymers. End-group modifications were performed to produce alkyne/biotin
      terminated copolymers which were further employed to generate dye-incorporated
      polymer-protein hybrids via the biotin-avidin interaction with avidin or "click"
      bioconjugation with azide-modified BSA. We have overcome two fundamental
      limitations in the synthesis of bioconjugates: (a) the basic restriction in the
      diversity of copolymers which can be synthesized for producing bioconjugates, (b)
      the limitation in the number of dyes/drug molecules that can be attached per
      protein molecule. The copolymers possessed enhanced optical properties compared
      to the dye due to increased solubility in water. Potential utility of these
      copolymers and conjugates in multiwell plate based assays, cell surface imaging
      and in vivo animal imaging were explored.

PMID- 19588922
TI  - Epimerization of cypermethrin stereoisomers in alcohols.
AB  - Isomerization induced by light, heat, and organic solvents has been shown to
      occur for some pyrethroid insecticides. Alcohols are popular solvents that are
      used in sample extraction, storage, and analysis. Thus, alcohol-induced
      epimerization may contribute to the incorrect interpretation of results from
      enantioselective chemical analysis and bioassay of pyrethroids like cypermethrin.
      In this study, we investigated the relationship between the rate of epimerization
      of cypermethrin stereoisomers: 1R-cis-alphaR and 1R-trans-alphaR and short-chain
      alkyl alcohol properties. In this study, complete epimerization of 1R-cis-alphaR
      produced an almost equal fraction of 1R-cis-alphaS, and that of 1R-trans-alphaR
      yielded 1R-trans-alphaS. For both stereoisomers, epimerization was most rapid in
      ethanol. The same stereoisomers underwent relatively rapid epimerization in
      methanol, n-propanol, 2-methyl-1-propanol, and n-butanol but were stable in 2
      butanol, suggesting that secondary alcohols have reduced reactivity, likely due
      to steric hindrance. We further evaluated epimerization of 1R-cis-alphaR and 1R
      trans-alphaR stereoisomers of cypermethrin as a function of water content in
      methanol. The presence of water in methanol generally increased the epimerization
      rate. For 1R-cis-alphaR, epimerization was most rapid with a water content of <
      or =2%, while for 1R-trans-alphaR, epimerization was most rapid with a water
      content of 10%. Results from this study clearly show that contact with commonly
      used primary alcohols may result in rapid abiotic epimerization, underscoring the
      importance of considering configurational stability in ensuring the analytical
      integrity and correct interpretation of bioassay data for stereoisomers of
      cypermethrin and similar pyrethroids.

PMID- 19588921
TI  - Epidermal growth factor tethered through coiled-coil interactions induces cell
      surface receptor phosphorylation.
AB  - We have elaborated and validated a novel approach for the oriented tethering of
      proteins such as the epidermal growth factor (EGF) on aminated surfaces. The
      grafting reactions were optimized to generate a dense and homogeneous EGF layer.
      Impact of EGF orientation on A-431 cellular response was investigated. Our
      results demonstrate that, in sharp contrast to responses obtained with soluble
      EGF supply or with randomly grafted EGF, oriented immobilization of EGF via a de
      novo designed coiled-coil capture system leads to a sustained phosphorylation of
      A-431 cell surface EGF receptors. Our results thus indicate that oriented protein
      immobilization via coiled-coil interactions is an efficient and versatile method
      to control tethering of bioactive molecules for future applications in the field
      of regenerative medicine and tissue engineering.

PMID- 19588923
TI  - Purification and characterization of a Kunitz-type trypsin inhibitor from Acacia
      victoriae Bentham seeds.
AB  - An Acacia victoriae trypsin inhibitor (AvTI) was purified from the seeds of
      prickly wattle (A. victoriae Bentham) by salt precipitation, ion exchange, and
      gel filtration chromatography and then characterized by electrophoresis and N
      terminal amino acid sequencing. AvTI had a specific activity of 138.99 trypsin
      inhibitor units per milligram (TIU mg(-1)), which was 21-fold higher than that of
      the salt precipitate. A molecular mass of 13 kDa was estimated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions,
      which also indicated that AvTI may consist of two polypeptide chains linked by at
      least one disulfide bond. Although only a single peak was resolved by ion
      exchange and reverse phase high-performance liquid chromatography (RP-HPLC),
      native-PAGE and isoelectric focusing revealed the presence of three isoforms
      possessing acidic pI values of 5.13, 4.76, and 4.27, respectively. N-Terminal
      amino acid sequencing analysis of native and reduced AvTI showed two sequences
      with a high degree of homology with a typical Kunitz-type trypsin inhibitor. All
      isoforms had considerable trypsin inhibitory activity but showed relatively very
      low inhibition against alpha-chymotrypsin.

PMID- 19588924
TI  - Sphere versus cylinder: the effect of packing on the structure of nonionic C12E6
      micelles.
AB  - Two independent series of calculations are performed simulating spherical and
      cylindrical C12E6 micelles in a temperature range around the experimental sphere
      to-rod transition temperature for surfactant concentrations less than 20% by
      weight. A comparative analysis of these systems helps to shed light on the
      microscopic details of the micelle sphere-to-rod transition. In agreement with
      theoretical models, we find that spherical and cylindrical micelles have a
      different oil core packing; the core radius of a cylindrical micelle is reduced
      by a factor of 0.87 with respect to the core radius of a spherical micelle.
      Despite this contraction, the specific volume of the alkyl tails is larger in a
      cylindrical micelle than in a spherical micelle. In both geometries, this
      specific volume follows the same linear increase with temperature. Density
      measurement experiments are also performed in order to evaluate the specific
      volume of the hydrophobic tail of surfactants of the C12Ej family with j ranging
      from 5 to 8. We observe a good agreement between experimental data and simulation
      results. Our simulations also show that the spatial distribution of the head
      groups in the interface is more effective in screening the oil core in the
      cylindrical aggregate than in the spherical aggregate, reducing by a factor of 2
      the oil surface per monomer exposed to water. This screening accounts for a free
      energy difference of Deltafs=fssph-fscyl approximately +2.5kBT per monomer and
      mirrors the essential role that the hydrophobic interactions have on the shape
      transition. We also find that the different interface packing correlates with
      different conformations and flexibility of the hydrophilic fragments E6, that
      appear as an entropic reservoir for the transition. Finally, comparing the degree
      of hydration of a spherical micelle at T=283 K with that of a cylindrical micelle
      at T=318 K, we observe an amount of dehydration in agreement with reported
      experimental data across the sphere-to-rod transition. However, for aggregates of
      fixed shape, we find a much smaller amount of dehydration with temperature,
      suggesting that the shape transition is not a consequence of the measured
      temperature dehydration but rather the opposite.

PMID- 19588925
TI  - Chemical components and tyrosinase inhibitors from the twigs of Artocarpus
      heterophyllus.
AB  - An HPLC method was developed and validated to compare the chemical profiles and
      tyrosinase inhibitors in the woods, twigs, roots, and leaves of Artocarpus
      heterophyllus . Five active tyrosinase inhibitors including dihydromorin,
      steppogenin, norartocarpetin, artocarpanone, and artocarpesin were used as marker
      compounds in this HPLC method. It was discovered that the chemical profiles of A.
      heterophyllus twigs and woods are quite different. Systematic chromatographic
      methods were further applied to purify the chemicals in the twigs of A.
      heterophyllus. Four new phenolic compounds, including one isoprenylated 2
      arylbenzofuran derivative, artoheterophyllin A (1), and three isoprenylated
      flavonoids, artoheterophyllin B (2), artoheterophyllin C (3), and
      artoheterophyllin D (4), together with 16 known compounds, were isolated from the
      ethanol extract of the twigs of A. heterophyllus. The structures of compounds 1-4
      were elucidated by spectroscopic analysis. However, the four new compounds did
      not show significant inhibitory activities against mushroom tyrosinase compared
      to kojic acid. It was found that similar compounds, such as norartocarpetin and
      artocarpesin in the twigs and woods of A. heterophyllus, contributed to their
      tyrosinase inhibitory activity.

PMID- 19588926
TI  - Determination of the mechanism of action of anti-FasL antibody by epitope mapping
      and homology modeling.
AB  - Fas ligand (FasL) is a 40-kDa type II transmembrane protein belonging to the
      tumor necrosis factor (TNF) family of proteins and binds to its specific
      receptor, Fas, a member of the TNF receptor family. Membrane-bound FasL can be
      processed into a soluble form by a metalloprotease similar to that which cleaves
      TNFalpha. Elevated levels of FasL have been implicated in a wide variety of
      diseases ranging from cancer to inflammatory abnormalities, which could be
      targeted by antibody therapy. We generated a fully human high-affinity antibody
      against FasL that binds to and neutralizes the activity of both soluble and
      membrane-associated human FasL. In order to elucidate the mechanism of function
      of this antibody, we have mapped the region and critical residues involved in the
      recognition of FasL using a combination of homology modeling,
      immunoprecipitation, hydrogen-deuterium exchange mass spectrometry (H/DXMS), and
      alanine scanning site-directed mutagenesis. These studies have revealed the
      antibody binding site on human FasL. Furthermore, through molecular homology
      modeling, we have proposed a mechanism for the neutralizing activity of this
      antibody that involves interference with the docking of the ligand to its
      receptor by the antibody.

PMID- 19588928
TI  - Apical ligand substitution, shape recognition, vapor-adsorption phenomenon, and
      microcalorimetry for a pillared bilayer porous framework that shrinks or expands
      in crystal-to-crystal manners upon change in the cobalt(II) coordination
      environment.
AB  - A 2D pillared bilayer coordination polymer, [Co(5-NH(2)-bdc)(bpy)(0.5)(H(2)O)] x
      2 H(2)O (1; 5-NH(2)-bdc = 5-aminoisophthalate; bpy = 4,4'-bipyridine) has been
      hydrothermally synthesized and shows a novel microporous host framework with 1D
      channels and high thermal stability (approximately 400 degrees C). The framework
      of 1 exhibits reversible single-crystal-to-single-crystal transformations upon
      removing and rebinding the coordinated waters as well as replacing them with MeOH
      and EtOH from the solvent. X-ray crystallography reveals that the coordination
      geometry of Co(II) changes from octahedron to square pyramid, as well as the
      shrinkage/expansion of pore deformation in respect to the subsequent shear motion
      of bpy pillars and vice versa. The dehydrated form 2 exhibits a shape recognition
      ability, which can accommodate linear molecules, such as MeCN and 2-propynyl
      alcohol, and interesting storage capabilities for oversized MeOH, EtOH, and
      benzene molecules, concomitant with spongelike dynamic transformation. The
      microcalorimetric study indicates that the crystalline state-liquid guest
      exchange and guest inclusion processes (1 superset MeOH or EtOH, 2 superset MeOH,
      EtOH or MeCN) are feasibly endothermic reactions with the values of molar
      enthalpy, DeltaH(theta)(m), of +21.38(96), +12.68(85), +25.92(86), +17.03(57),
      and +14.93(75) kJ mol(-1), respectively.

PMID- 19588927
TI  - Identification of amino acids at two dimer interface regions of the alpha-factor
      receptor (Ste2).
AB  - The yeast alpha-factor pheromone receptor (Ste2) belongs to the large superfamily
      of G protein-coupled receptors (GPCRs) that characteristically contain seven
      transmembrane domains (TMs). A wide range of GPCRs are thought to exist as dimers
      or oligomers. To identify the interface regions that mediate oligomerization of
      Ste2, a set of 73 different mutants with Cys residues substituted near the
      extracellular ends of the transmembrane domains were screened for the ability to
      form intermolecular disulfide bonds. Disulfide bonds formed between Cys residues
      at six positions in Ste2. Cys substituted for Val-45 formed disulfide bonds,
      indicating contact between residues at the extracellular end of TM1. Disulfide
      bonds also formed with Cys residues substituted for five different residues
      clustered near the extracellular end of TM4 (Val-183, Val-186, Lys-187, Met-189,
      and Ile-190). Binding of the alpha-factor ligand to Ste2 did not change the sites
      at which cross-linking occurred in these TMs, but it did increase the efficiency
      of dimer formation for the Ste2-V183C mutant. Interestingly, oligomers of the
      class A family of vertebrate GPCRs are also thought to form homomeric contacts at
      TM1 and TM4. These results support the conclusion that GPCRs form oligomers and
      not just dimers, since TM1 and TM4 are too far apart in the class A GPCRs to form
      contacts in the same dimer moiety. Similar dimer interface sites in Ste2 and
      class A receptors provide further evidence that many aspects of structure and
      function are highly conserved across the divergent GPCR superfamily.

PMID- 19588929
TI  - Imaging the evolution of nanoscale photocurrent collection and transport networks
      during annealing of polythiophene/fullerene solar cells.
AB  - We use photoconductive atomic force microscopy to image nanoscale spatial
      variations in photocurrent across the surfaces of photovoltaic cells made from
      blends of the conjugated polymer regioregular poly(3-hexylthiopene) (P3HT) with
      phenyl-C(61)-butyric acid methyl ester (PCBM). We study how the spatial
      variations in photocurrent evolve with thermal annealing, and we correlate these
      changes with the evolution of macroscopic film and device properties such as
      external quantum efficiency and carrier mobility. We use conductive atomic force
      microscopy to examine the development of injection and transport networks for
      both electrons and holes as a function of annealing. We find that the hole
      transport, electron transport, and photocurrent collection networks become
      increasingly heterogeneous with thermal annealing and remain heterogeneous on the
      10-100 nm length scale even in the most efficient P3HT/PCBM devices. After
      annealing, the regions of the greatest dark hole currents, greatest dark electron
      currents, and greatest photocurrents are each associated with different regions
      of the nanostructured films. These results suggest spatial heterogeneity can
      contribute to the imperfect internal quantum efficiency even in relatively
      efficient organic photovoltaics and that fully 3D modeling is needed to describe
      the devices physics of polymer blend solar cells.

PMID- 19588931
TI  - Comparison of gas chromatography-coupled time-of-flight mass spectrometry and 1H
      nuclear magnetic resonance spectroscopy metabolite identification in white wines
      from a sensory study investigating wine body.
AB  - Metabolite profiles of white wines, including Chardonnay, Pinot gris, Riesling,
      Sauvignon blanc, and Viognier varieties, were determined using both gas
      chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) and proton
      nuclear magnetic resonance spectroscopy ((1)H NMR). A total of 108 metabolites
      were identified by GC-TOF-MS, and 51 metabolites were identified by (1)H NMR; the
      majority of metabolites identified include the most abundant compounds found in
      wine (ethanol, glycerol, sugars, organic acids, and amino acids). Compositional
      differences in these wines correlating to the wine sensory property "body", or
      viscous mouthfeel, as scored by a trained panel were identified using partial
      least-squares (PLS) regression. Independently calculated GC-TOF-MS and NMR-based
      PLS models demonstrate potential for predictive models to replace expensive, time
      consuming sensory panels. At the modeling stage, correlations between the
      measured and predicted values have coefficients of determination of 0.83 and 0.75
      for GC-TOF-MS and (1)H NMR, respectively. Additionally, the MS- and NMR-based
      models present new insights into the chemical basis for wine mouthfeel
      properties.

PMID- 19588932
TI  - 13C isotope-labeled metabolomes allowing for improved compound annotation and
      relative quantification in liquid chromatography-mass spectrometry-based
      metabolomic research.
AB  - Metabolomics is rapidly becoming an integral part of many life science studies
      ranging from disease diagnostics to systems biology. However, a number of
      problems such as the discrimination of biological from non-biological signals,
      efficient compound annotation, and reliable quantification are still not
      satisfactorily solved in untargeted LC-MS-based metabolomics research. Extending
      our previous work on direct infusion-based metabolomics, we here describe a (13)C
      isotope labeling strategy in combination with an Ultra Performance Liquid
      Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry-based
      approach (UPLC-FTICR MS) which provides a technological platform offering
      solutions to a number of the above-mentioned problems. We further demonstrate
      that the use of a fully labeled metabolome is not only beneficial for high end
      mass spectrometers, such as that used in this study but also provides a
      considerable improvement to every other mass spectrometry-based metabolomic
      platform.

PMID- 19588930
TI  - Macrocyclic diamide ligand systems: potential chelators for 64Cu- and 68Ga-based
      positron emission tomography imaging agents.
AB  - The N(4)-macrocyclic ligand 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12
      heptadeca-1(12),14,16-triene H(2)L has been synthesized by the [1 + 1]
      condensation reaction between N,N'-bis(chloroacetyl)-1,2-phenylenediamine and 1,3
      propylenediamine. The coordination chemistry of this ligand has been investigated
      with the metal ions Cu(II), Ni(II), Zn(II), and Ga(III) (complexes 1, 2, 3 and 4,
      respectively). H(2)L and its metal complexes have been fully characterized by the
      use of NMR, UV/vis, electron paramagnetic resonance, and elemental analysis where
      appropriate. The four metal complexes 1-4 have been structurally characterized by
      X-ray crystallography which confirmed that in all cases the amide nitrogen atoms
      are deprotonated and coordinated to the metal center. Complexes 3 and 4 are five
      coordinate with a water molecule and chloride ion occupying the apical site,
      respectively. Cyclic voltammetric measurements on complex 1 show that this
      complex is oxidized reversibly with a half-wave potential, E(1/2) = 0.47 V, and
      reduced irreversibly at E(P) = -1.84 V. Density functional theory calculations
      reproduce the geometries of the four complexes. The one-electron reduction and
      oxidation potentials for 1 were calculated by using two solvent models, DMF and
      H(2)O. The calculations indicated that the one electron oxidation of 1 may
      involve removal of an electron from the ligand as opposed to the metal center,
      producing a diradical. The diamide macrocyle is of interest for the development
      of new positron emission tomography (PET) and single photon emission computed
      tomography (SPECT) imaging agents, and a radiolabeled complex has been
      synthesized with the positron emitting isotope (64)Cu. In vivo biodistribution
      studies for the (64)Cu labeled complex, (64)Cu-1, in male Lewis rats, showed that
      the activity is cleared rapidly from the blood within 1-2 h post-administration.

PMID- 19588934
TI  - Design of a new histamine H3 receptor antagonist chemotype: (3aR,6aR)-5-alkyl-1
      aryl-octahydropyrrolo[3,4-b]pyrroles, synthesis, and structure-activity
      relationships.
AB  - A new histamine H3 receptor (H3R) antagonist chemotype 1 was designed by
      combining key pharmacophoric elements from two different precursor structural
      series and then simplifying and optimizing the resulting combined structural
      features. First, analogues were made based on a previously identified conessine
      based H3R antagonist series. While the first analogues 11 and 15 showed no
      antagonistic activity to H3R, the mere addition of a key moiety found in the
      reference compound 7 (ABT-239) elevated the series to high potency at H3R. The
      hybrid structure (16b) was judged too synthetically demanding to enable an
      extensive SAR study, thus forcing a strategy to simplify the chemical structure.
      The resulting (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrrole series
      proved to be highly potent, as exemplified by 17a having a human H3 K(i) of 0.54
      nM, rat H3 K(i) of 4.57 nM, and excellent pharmacokinetics (PK) profile in rats
      (oral bioavailability of 39% and t(1/2) of 2.4 h).

PMID- 19588936
TI  - Biomonitoring of carcinogenic heterocyclic aromatic amines in hair: a validation
      study.
AB  - A facile method was established to measure heterocyclic aromatic amines (HAAs)
      accumulated in human hair and rodent fur. The samples were digested by base
      hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase
      extraction. Quantification was done by liquid chromatography/tandem mass
      spectrometry, using a triple stage quadrupole mass spectrometer in the selected
      reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in the hair of six meat
      eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole
      (AalphaC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair
      from meat-eaters and six vegetarians. PhIP was detected in the hair from one
      vegetarian, and at a level just above the LOQ (65 pg/g hair), indicating that
      PhIP exposure occurs primarily through meat consumption. The levels of PhIP in
      hair samples from two meat-eaters varied by less than 24% over a 6 month
      interval, signifying that the exposure to PhIP and its accumulation in hair are
      relatively constant over time. In a controlled feeding study, female C57BL/6 mice
      were given these HAAs in their drinking water for 1 month, at six daily dose
      concentrations ranging from 0 and 0.080 to 800 microg/kg body weight. PhIP was
      detected in fur of mice at all doses, whereas AalphaC and MeIQx were detected in
      fur at dosages > or =0.8 mug AalphaC/kg body weight and > or =8 microg MeIQx/kg
      body weight. There was a strong positive relationship between dosage and each of
      the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p
      values < 0.0001); however, the levels of HAA in fur did not correlate to the
      levels of DNA adducts after adjustment of dose. Thus, hair appears to be a
      promising tissue with by which we can noninvasively biomonitor the chronic
      exposure to PhIP, a potential human carcinogen.

PMID- 19588937
TI  - Integrated comparison of drug-related and drug-induced ultra performance liquid
      chromatography/mass spectrometry metabonomic profiles using human hepatocyte
      cultures.
AB  - The biochemical variations induced in human primary hepatocyte cultures by
      reference activators of xenoreceptor CAR (NR1I3) and PXR (NR1I2), i.e.,
      rifampicin, phenobarbital, and 6-(4-chlorophenyl)imidazo[2,1-b] [1,3]thiazole-5
      carbaldehyde O-3,4-dichlorobenzyl) oxime (CITCO), were investigated using a
      global metabonomics approach. Cultured human hepatocytes were treated with the
      three drugs before analysis of intracellular and extracellular media by ultra
      performance liquid chromatography/time-of-flight-mass spectrometry (UPLC/TOF-MS)
      technique, in order to list endogenous compounds potentially related to a PXR or
      CAR induction mechanism and to identify drug metabolites related to each
      treatment. The emphasis was put on the quality of the analytical data
      (dilution/filtration strategy before data processing) and on the appropriate
      pattern recognition techniques. In cellular media, the most significant
      variations seen in the data are not related to the treatments but to the source
      of hepatocytes, illustrating the importance of the genetic and/or environmental
      background in human liver experiments. However when applying classical
      multivariate statistical approaches (principal component analysis (PCA) and
      orthogonal partial least squares (O-PLS)), the statistical weight due to drug
      metabolites, present only in the treated groups, hinders the interpretation
      because of their predominance compared to most of the changes seen in endogenous
      metabolites. A new statistical approach, called shared and unique structure (SUS)
      plot, enabling the comparison of different treatments having the same control has
      been applied, allowing separation of clearly exogenous variables (drug
      metabolites) from endogenous biomarkers. Endogenous variables (either up- or down
      regulated) have been attributed specifically to the impact of rifampicin (PXR
      ligand), CITCO (CAR ligand), and phenobarbital (CAR and PXR activator) on the
      biological regulation pathways of the hepatocytes. This global approach coupled
      to a statistical pretreatment of the data, enabling the separate capture of both
      drug related and drug induced biomarkers, represents a powerful technique for
      future mechanistic studies using cellular tools.

PMID- 19588935
TI  - Structure-activity relationship and comparative docking studies for cycloguanil
      analogs as PfDHFR-TS inhibitors.
AB  - Drug resistance acquired by Plasmodium falciparum (Pf) is a major problem in the
      treatment and control of malaria. One of the major examples of drug resistance is
      that caused by mutations in the active site of dihydrofolate reductase (DHFR) of
      Pf (PfDHFR-TS). A double mutation, A16V+S108T, is specific for resistance to the
      marketed drug cycloguanil. In this study, we used 58 cycloguanil (2,4-diamino-1,6
      dihydro-1,3,5-triazine) derivatives to explore the relationship between various
      physicochemical properties and reported binding affinity data on wild-type and
      mutant-type A16V+S108T. Using the Hansch 2D-quantitative structure-activity
      relationship method, we obtained a parabolic relationship of hydrophobicity of
      substituents at the N1-phenyl ring with the wild-type binding affinity data.
      Hydrophobicity being a key property for wild-type binding affinity data, we found
      steric factors to be crucial for A16V+S108T mutant resistance. We investigated
      FlexX, GOLD, Glide and Molegro virtual docking programs and 13 different scoring
      functions on 10 of the cycloguanil derivatives to evaluate which program was best
      for reproducing the experimental binding mode and correlating the docking scores
      with the reported binding affinity data. We identified GOLD, using its GoldScore
      fitness function, as the most accurate docking program for predicting binding
      affinity data of cycloguanil derivatives to DHFR and Molegro virtual docker, with
      its template docking algorithm and MolDock [GRID] scoring function, as most
      accurate for reproducing the experimental binding mode of a reference ligand that
      is structurally similar to the cycloguanil derivatives studied. We also report an
      interaction index which best describes the structure-activity relationships
      exhibited by these analogs in terms of PfDHFR-TS active site interactions.

PMID- 19588938
TI  - Phospholipid-induced fibrillation of a prion amyloidogenic determinant at the
      air/water interface.
AB  - The peptide fragment 106-126 of prion protein [PrP(106-126)] is a prominent
      amyloidogenic determinant. We present analysis of PrP(106-126) fibrillation at
      the air/water interface and, in particular, the relationship between the
      fibrillation process and interactions of the peptide with phospholipid
      monolayers. We find that lipid monolayers deposited at the air/water interface
      induce rapid formation of remarkably highly ordered fibrils by PrP(106-126), and
      that the extent of fibrillation and fiber organization were dependent upon the
      presence of negatively charged and unsaturated phospholipids in the monolayers.
      We also observe that fibrillation was enhanced when PrP(106-126) was injected
      underneath preassembled phospholipid monolayers, compared to deposition and
      subsequent compression of mixed monolayers of the peptide and phospholipids. In a
      broader context, this study demonstrates that Langmuir systems constitute a
      useful platform for studying lipid interactions of amyloidogenic peptides and
      lipid-induced fibrillation phenomena.

PMID- 19588939
TI  - Nanostructured colloidal crystals from forced hydrolysis methods.
AB  - In this work, an original route for ZnO nanostructured spherical colloids and
      their assembly into colloidal crystals are presented. The temporal evolution of
      crystal size and shape was followed by X-ray diffraction and the colloids size
      distribution by scanning electron microscopy. These spherical colloids showed a
      change in their size dispersion with aging time. Early stage suspensions, with a
      narrow size distribution, were settled to the bottom and dried with a slow
      evaporation rate to obtain colloidal crystals. This original route provides a new
      material for future applications in opalline photonic crystals, with a dielectric
      constant higher than that of classical materials (silica and latex). Moreover,
      this route means an improvement of previously reported data from the literature
      since it involves a one-pot strategy and room-temperature colloid assembly.

PMID- 19588941
TI  - pH-responsive reversibly swellable nanotube arrays.
AB  - We demonstrate a technique for synthesizing substrate-bound arrays of
      submicrometer-sized reversibly swellable tubes by using porous templates. The
      sacrificial template approach allows straightforward control over the tube
      length, diameter, and lateral arrangement of the resultant surface-bound
      nanotubes. We also explored methods for varying the tube opening structure by
      altering the pore shape at the surface of the template. A specific PEM system
      composed of poly(allylamine hydrochloride) and poly(acrylic acid) was chosen as
      the building block for the nanotube arrays because of its ability to undergo pH
      triggered swelling-deswelling transitions. The activation of this transition
      results in dramatic changes in the length and diameter of the nanotubes as
      characterized in situ via confocal laser scanning microscopy (CLSM). The pH
      driven reversible swelling-deswelling and nanoporosity behavior observed with
      planar films and nanotubes of this PEM system is a direct consequence of the
      breaking and reforming of ionic cross-links.

PMID- 19588940
TI  - Synthesis of biocompatible sterically-stabilized poly(2-(methacryloyloxy)ethyl
      phosphorylcholine) latexes via dispersion polymerization in alcohol/water
      mixtures.
AB  - Poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) is soluble in either 2
      propanol or water but becomes insoluble in certain alcohol-rich 2-propanol/water
      mixtures. We have exploited this unusual cononsolvency behavior in order to
      prepare new biocompatible sterically stabilized PMPC latexes via nonaqueous
      dispersion polymerization in 2-propanol/water mixtures. All polymerizations were
      conducted in the presence of monomethoxy-capped poly(ethylene glycol)
      methacrylate (PEGMA) as a reactive stabilizer, with some formulations including
      ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Under optimized
      conditions, unimodal size distributions could be obtained with a mean latex
      diameter of approximately 1 microm, as judged by laser diffraction and DLS. The
      mean latex diameter depended on both the PEGMA and initiator concentration but
      was almost independent of the cross-linking density. Smaller PMPC latexes were
      obtained by increasing the alcohol content of the dispersion medium. On dilution
      with water, these latexes acquired microgel character. The microgel solution
      viscosity was insensitive to added salt due to the so-called
      "antipolyelectrolyte" effect, which is characteristic of polyzwitterions.
      Finally, copolymerization of MPC with a fluorescein-based methacrylic comonomer
      produced fluorescently labeled PMPC latexes, which may have potential biomedical
      applications.

PMID- 19588942
TI  - Functionalization of delaminated zeolite ITQ-6 for the adsorption of carbon
      dioxide.
AB  - Novel functionalized adsorbents for CO(2) separation were synthesized by grafting
      3-aminopropyl, 3-(methylamino)propyl, or 3-(phenylamino)propyl ligands in the
      delaminated zeolite ITQ-6. On the basis of the texture parameters determined from
      nitrogen adsorption isotherms recorded at 77 K and the results of chemical
      analysis, physicochemical properties of functionalized ITQ-6 were evaluated and
      compared with those of mesoporous SBA-15 silica functionalized with the same
      ligands. To examine carbon dioxide adsorption on functionalized materials,
      adsorption isotherms at 293 K were measured. To obtain information on the surface
      energetics of CO(2) adsorption on selected samples, isotherms were taken in the
      temperature range from 273 to 333 K and adsorption isosteres were calculated.
      Isosteric adsorption heats determined from the slope of adsorption isosteres
      proved that all of the 3-aminopropyl ligands in ITQ-6 take part in CO(2)
      adsorption. It was found that in the whole region of CO(2) pressures the
      efficiency of the amine ligand, defined as the number of adsorbed CO(2) molecules
      per one amine ligand, is higher for functionalized ITQ-6 than for functionalized
      SBA-15 silica.

PMID- 19588943
TI  - Self-organization pathways and spatial heterogeneity in insulin amyloid fibril
      formation.
AB  - At high temperature and low pH, the protein hormone insulin is highly prone to
      form amyloid fibrils, and for this reason it is widely used as a model system to
      study fibril formation mechanisms. In this work, we focused on insulin
      aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 degrees C. By
      means of in situ Thioflavin T (ThT) staining, the kinetics profiles were
      characterized as a function of the protein concentration, and two concurrent
      aggregation pathways were pointed out, being concentration dependent. In
      correspondence to these pathways, different morphologies of self-assembled
      protein molecules were detected by atomic force microscopy images also evidencing
      the presence of secondary nucleation processes as a peculiar mechanism for
      insulin fibrillation. Moreover, combining ThT fluorescence and light scattering,
      the early stages of the process were analyzed in the low concentration regime,
      pointing out a pronounced spatial heterogeneity in the formation of the first
      stable fibrils in solution and the onset of the secondary nucleation pathways.

PMID- 19588944
TI  - Mixed surfactant based microemulsions as vehicles for enhanced solubilization and
      synthesis of organoselenium compounds.
AB  - We exploited the added degree of compositional freedom provided by mixed
      AOT/lecithin surfactants in reverse isooctane microemulsion to demonstrate that a
      small amount of added lecithin significantly enhances the solubility of
      organodiselenides over that in AOT reverse isooctane microemulsions alone.
      Conductivity results show that the added lecithin significantly increases the
      solubility of four different organodiselenides and raises the temperature
      required to induce percolation. FTIR, (1)H NMR, and UV-visible techniques were
      utilized to gain insight into the interactions of organodiselenides, AOT and
      lecithin headgroups with water in the micellar core. The information obtained
      from these experiments was used to design a novel synthetic route for preparing 4
      chloro-2-(naphthalen-2-ylselanyl) pyrimidine in reverse microemulsion.

PMID- 19588946
TI  - Endowing carbon black pigment particles with primary amino groups.
AB  - A readily synthetic route to endow the surface of hydrophobic carbon black (CB)
      particles with primary amino groups has been developed. The adsorption of the
      water-borne polyelectrolyte copolymer poly(vinyl amine-co-vinyl amide) (PVAm) on
      CB was studied as function of pH and polyelectrolyte concentration. The amino
      functionalization process of CB with PVAm strongly depends on pH. As shown by
      electrokinetic measurement as function of pH, the content of accessible primary
      amino groups on the surface of CB increases with increasing the OH-
      concentration. The alternative functionalization of the CB surface with an
      anionic polyelectrolyte is demonstrated for the adsorption of poly(ethylene-alt
      maleic anhydride) (PEMSA). About 50 mg of PVAm can be adsorbed on 1.0 g of CB,
      which is sufficient to completely alter the surface net charge. The aim of the
      introduced functional amino groups is their ability to act as anchoring groups
      for subsequent surface reactions improving the CB's process ability,
      compatibility, and adhesion properties.

PMID- 19588945
TI  - The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H
      cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue: synthesis,
      molecular pharmacology, and biostructural characterization.
AB  - The design, synthesis, and pharmacological characterization of a highly potent
      and selective glutamate GluR5 agonist is reported. (S)-2-Amino-3-((RS)-3-hydroxy
      8-methyl-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (5) is the 8
      methyl analogue of (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol
      4-yl)propionic acid ((S)-4-AHCP, 4). Compound 5 displays an improved selectivity
      profile compared to 4. A versatile stereoselective synthetic route for this class
      of compounds is presented along with the characterization of the binding affinity
      of 5 to ionotropic glutamate receptors (iGluRs). Functional characterization of 5
      at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show
      a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid
      (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid
      ((S)-ATPA, 3) as previously demonstrated for 4. An X-ray crystallographic
      analysis of 4 and computational analyses of 4 and 5 bound to the GluR5 agonist
      binding domain (ABD) are presented, including a watermap analysis, which suggests
      that water molecules in the agonist binding site are important selectivity
      determinants.

PMID- 19588947
TI  - When sugars get wet. A comprehensive study of the behavior of water on the
      surface of oligosaccharides.
AB  - In this article, we characterize the behavior of water on the surface of a
      diverse group of carbohydrates and attempt to determine the role of saccharide
      size, linkage, and branching as well as secondary structure on the dynamics and
      structure of water at the surface. In order to better understand the similarities
      and differences in the behavior of the solvent on the carbohydrate surface, we
      explore residence times, rotational correlation functions, local solvent
      occupancy numbers, and diffusivities. We find that due to the differences in
      secondary structure water residence times are longer and translational and
      rotational dynamics are retarded when in contact with wide helices and branched
      sugars. In the case of extended helices and smaller oligosaccharides, water
      dynamics is faster and less hindered. This indicates that branching, the type of
      linkage between monomers, and the anomeric configuration all play a major role in
      determining the structure and dynamics of water on the surface of carbohydrates.

PMID- 19588948
TI  - Decoding the pattern of photon colors in single-molecule FRET.
AB  - Conformational dynamics of a single molecule can be studied using Forster
      resonance energy transfer (FRET) by recording a sequence of photons emitted by a
      donor and an acceptor dye attached to the molecule. We describe a simple and
      robust method to estimate the rates of transitions between different
      conformational states and the FRET efficiencies associated with these states. For
      a photon trajectory with measured interphoton times, the pattern of colors is
      decoded by maximizing the appropriate likelihood function. This approach can be
      used to analyze bursts of photons from diffusing molecules as well as photon
      trajectories generated by immobilized molecules. The procedure is illustrated
      using simulated photon trajectories corresponding to two-state and three-state
      molecules. The method works even when the photon colors appear to be scrambled
      because of high background noise, the photophysical properties of the conformers
      are similar, or the conformational and photon count rates are comparable. The
      consistency of the model with the data can be checked by recoloring the photon
      trajectories and comparing the predicted and observed FRET efficiency histograms.

PMID- 19588949
TI  - Understanding the structure of aqueous cesium chloride solutions by combining
      diffraction experiments, molecular dynamics simulations, and reverse Monte Carlo
      modeling.
AB  - A detailed study of the microscopic structure of an electrolyte solution, cesium
      chloride (CsCl) in water, is presented. For revealing the influence of salt
      concentration on the structure, CsCl solutions at concentrations of 1.5, 7.5, and
      15 mol % are investigated. For each concentration, we combine total scattering
      structure factors from neutron and X-ray diffraction and 10 partial radial
      distribution functions from molecular dynamics simulations in one single
      structural model, generated by reverse Monte Carlo modeling. This combination of
      computer modeling methods is capable of (a) showing the extent to which
      simulation results are consistent with experimental diffraction data and (b)
      tracking down distribution functions in computer simulation that are the least
      comfortable with diffraction data. For the present solutions, we show that the
      level of consistency between simulations that use simple pair potentials and
      experimental structure factors is nearly quantitative. Remaining inconsistencies
      seem to be caused by water-water distribution functions. Changing the pair
      potentials of water-water interactions from SPC/E to TIP4P-2005 has not had any
      effect in this respect. As a final result, we obtained particle configurations
      from reverse Monte Carlo modeling that were in quantitative agreement with both
      diffraction data and most of the molecular dynamics (MD) simulated partial radial
      distribution functions (prdf's). From the particle coordinates, the distribution
      of the number of first neighbors, as well as angular correlation functions, were
      calculated. The average number of water molecules around cations decreases from
      about 8 to about 6.5 as concentration increases from 1.5 to 15 mol %, whereas the
      same quantity for the anions changes from about 7 to about 5. It was also found
      that the average angle of Cl...H-O particle arrangements, characteristic of anion
      water hydrogen bonds, is closer to 180 degrees than that found for O...H-O
      arrangements (water-water hydrogen bonds). The present combination of
      experimental and computer simulation methods appears to be promising for the
      study of other electrolyte solutions.

PMID- 19588950
TI  - Development and application of FI catalysts for olefin polymerization: unique
      catalysis and distinctive polymer formation.
AB  - Catalysts contribute to the efficient production of chemicals and materials in
      almost all processes in the chemical industry. The polyolefin industry is one
      prominent example of the importance of catalysts. The discovery of Ziegler-Natta
      catalysts in the 1950s resulted in the production of high-density polyethylenes
      (PEs) and isotactic polypropylenes (iPPs). Since then, further catalyst
      development has led to the production of a new series of polyolefins, including
      linear low-density PEs, amorphous ethylene/1-butene copolymers,
      ethylene/propylene/diene elastomers, and syndiotactic PPs (sPPs). Polyolefins are
      now the most important and the most produced synthetic polymers. This Account
      describes a family of next-generation olefin polymerization catalysts (FI
      catalysts) that are currently being used in the commercial production of value
      added olefin-based materials. An FI catalyst is a heteroatom-coordinated early
      transition metal complex that combines a pair of nonsymmetric phenoxy-imine [O(
      ), N] chelating ligands with a group 4 transition metal. The catalytically active
      species derived from FI catalysts is highly electrophilic and can assume up to
      five isomeric structures based on the coordination of the phenoxy-imine ligand.
      In addition, the accessibility of the ligands of the FI catalysts and their
      amenability to modification offers an opportunity for the design of diverse
      catalytic structures. FI catalysts exhibit many unique chemical characteristics:
      precise control over chain transfers (including highly controlled living ethylene
      and propylene polymerizations), extremely high selectivity for ethylene, high
      functional group tolerance, MAO- and borate-free polymerization catalysis,
      significant morphology polymer formation, controlled multimodal behavior, high
      incorporation ability for higher alpha-olefins and norbornene, and highly
      syndiospecific and isospecific polymerizations of both propylene and styrene.
      These reactions also occur with very high catalyst efficiency. The reaction
      products include a wide variety of unique olefin-based materials, many of which
      were previously unavailable via other means of polymerization. We have produced
      selective vinyl- and Al-terminated PEs, ultrahigh molecular weight linear PEs,
      regio- and stereoirregular high molecular weight poly(higher alpha-olefin)s,
      ethylene- and propylene-based telechelic polymers, a wide array of polyolefinic
      block copolymers from ethylene, propylene, and higher alpha-olefins, and
      ultrafine noncoherent PE particles. FI catalysts are important from the
      organometallic, catalytic, and polymer science points of view, and the chemical
      industry is now using them for the production of value-added olefin-based
      materials. We anticipate that future research on FI catalysts will produce
      additional olefin-based materials with unique architectures and material
      properties and will offer scientists the chance to further study olefin
      polymerization catalysis and related reaction mechanisms.

PMID- 19588951
TI  - Thermal properties and ionic conductivity of imidazolium
      bis(trifluoromethanesulfonyl)imide dicationic ionic liquids.
AB  - We report on the thermal and transport properties of new dicationic ionic
      liquids. The new ionic liquids are based on the
      bis(trifluoromethanesulfonyl)imide [NTf(2)](-) anion and a cation that contains
      two imidazolium rings, connected by either a pentane or a decane hydrocarbon
      chain and different side groups. We have investigated the conductivity and the
      thermal properties by dielectric spectroscopy and differential scanning
      calorimetry, respectively. Our results show that the length of the alkyl chain on
      the cation has no, or weak, influence on the glass transition temperature, T(g),
      whereas the presence of rigid aromatic side groups has a strong influence
      increase T(g). The highest ionic conductivity is 5.9 x 10(-4) S cm(-1) at 298 K
      for an ionic liquid with a decane chain and one methyl group on each imidazolium
      ring. The conductivity results correlate well with the glass transition
      temperatures. This shows that the flexibility of the geminal cations is very
      important for the conductivity. However, the presence of nonflexible aromatic
      side groups on the imidazolium ring decreases the flexibility and hence the
      mobility.

PMID- 19588952
TI  - Surface science investigations of oxidative chemistry on gold.
AB  - Because of gold's resistance to oxidation and corrosion, historically chemists
      have considered this metal inert. However, decades ago, researchers discovered
      that highly dispersed gold particles on metal oxides are highly chemically
      active, particularly in low-temperature CO oxidations. These seminal findings
      spurred considerable interest in investigations and applications of gold-based
      materials. Since the discovery of gold's chemical activity at the nanoscale,
      researchers found that bulk gold also has interesting catalytic properties. Thus,
      it is important to understand and contrast the intrinsic chemical properties of
      bulk gold with those of nanoparticle Au. Despite numerous studies, the structure
      and active site of supported Au nanoclusters and the active oxygen species remain
      elusive, and model studies under well-controlled conditions could help identify
      these species. The {111} facet has the lowest surface energy and is the most
      stable and prevalent configuration of most supported gold nanoparticles.
      Therefore, a molecular-level understanding of the physical properties and surface
      chemistry of Au(111) could provide mechanistic details regarding the nature of Au
      based catalysts and lead to improved catalytic processes. This Account focuses on
      our current understanding of oxidative chemistry on well-defined gold single
      crystals, predominantly from recent investigations on Au(111) that we have
      performed using modern surface science techniques. Our model system strategy
      allows us to control reaction conditions, which assists in the identification of
      reaction intermediates, the determination of the elementary reaction steps, and
      the evaluation of reaction energetics for rate-limiting steps. We have employed
      temperature-programmed desorption (TPD), molecular beam reactive scattering
      (MBRS), and Auger electron spectroscopy (AES) to evaluate surface oxidative
      chemistry. In some cases, we have combined these results with density functional
      theory (DFT) calculations. By controlling the reaction parameters that determine
      product selectivity, we have examined the chemical properties of bulk gold. Based
      on our investigations, the surface-bound oxygen atoms are metastable at low
      temperature. We also demonstrate that the oxygen atoms and formed hydroxyls are
      responsible for some of the distinct chemical behavior of gold and participate in
      surface reactions either as a Bronsted base or a nucleophilic base. We observe
      similar reaction patterns on gold surfaces to those on copper and silver
      surfaces, suggesting that the acid-base reactions that have been observed on
      copper and silver may also occur on gold. Our model chemical studies on gold
      surfaces have provided intrinsic fundamental insights into high surface area gold
      based catalysts and the origin of the reactive oxygen species.

PMID- 19588953
TI  - Comparing the reactivity of alkynes and alkenes on silicon (100) surfaces.
AB  - The relative reactivities of alkynes to alkenes on hydrogen-terminated silicon
      (100) surfaces, under conditions where a monolayer will be produced via
      hydrosilylation, were measured using two different approaches. The first approach
      was to form monolayers from a series of solutions containing different mole
      fractions of an alkyne, with a trifluorothioacetate distal moiety and an alkene
      with a terminal carboxylic acid functional. X-ray photoelectron spectroscopic
      analysis of the resultant surfaces showed that the mole fraction of alkyne on the
      surface was larger than that in the respective alkyne/alkene mixture. By fitting
      the XPS data, we estimated that the reactivity ratio of alkyne to alkene was
      approximately 1.7 +/- 0.2 when monolayers were formed at 120 degrees C. The
      second approach was using a molecule containing both an alkyne at one end and an
      alkene at the other, non-1-yne-8-ene, as the hydrosilylation reagent such that
      either end could attach to the silicon surface. The relative orientation of this
      molecule, once reacted with a hydrogen-terminated Si(100) surface, was determined
      by coupling an additional reagent to the distal end of the monolayer. The reagent
      used was azidoferrocene, which could attach onto free alkyne moieties on the
      surface only via the 1,3-Huisgen cycloaddition "click" reaction. Electrochemical
      analysis was then used to determine how many ferrocene moieties were attached to
      the SAM surface. In this way, it was shown that the alkyne end reacted
      preferentially with the silicon surface compared with the alkene end. The
      reactivity ratio of the alkyne end to the alkene end was increased from 2.0 +/-
      0.2 to 9 +/- 1 when the temperature was decreased from 120 to 65 degrees C.

PMID- 19588954
TI  - Probing the stability of magnetically assembled DNA-linked colloidal chains.
AB  - The self-assembly of colloidal particles using DNA linker molecules has led to
      novel colloidal materials. This article describes the development and
      characterization of a new class of colloidal structures based on the directed
      assembly of DNA-linked paramagnetic particles. A key obstacle to assembling these
      structures is understanding the fundamental chemistry and physics of the assembly
      processes. The stability of these cross-linked chain structures is the first step
      toward reliable assembly and thus important for its applications; however, chain
      stability has yet to be systematically studied. In this paper, we investigate
      both theoretically and experimentally, the stability of DNA-linked paramagnetic
      colloidal chains as a function of externally applied magnetic field strength and
      surface grafted DNA length and density. A total interparticle free energy
      potential model is developed accounting for all major forces contributing to
      chain stability, and a phase diagram is obtained from experiments to illustrate
      linked chain phases, unstable unlinked particle phases, and their transitions,
      which agree well with those predicted by the model. From this study, optimized
      parameters for successful linking and building stable linked chains are obtained.

PMID- 19588955
TI  - Effects of ligand coordination number and surface curvature on the stability of
      gold nanoparticles in aqueous solutions.
AB  - The colloidal stability of gold nanoparticles (AuNPs) cap-exchanged with either
      monothiol- or dithiolane-terminated PEG-OCH(3) ligands was investigated. Three
      distinct aspects were explored: (1) effects of excess salt concentration; (2)
      ligation competition by dithiothreitol (DTT); and (3) resistance to sodium
      cyanide digestion. We found that overall ligands presenting higher coordination
      numbers (dithiolane) exhibit much better stability to excess added salt and
      against competition from DTT compared to their monodentate counterparts.
      Resistance to NaCN digestion indicated that there is a balance between
      coordination number and density of ligand packing on the NP surface. For smaller
      NPs, where a larger surface curvature reduces the ligand packing density, a
      higher coordination number is clearly beneficial. In comparison, a higher ligand
      density allowed by the smaller curvature for larger nanocrystals makes monothiol
      PEG-capped NPs more resistant to cyanide digestion. The present study indicates
      that balance between the coordination number and surface packing density is
      crucial to enhancing the colloidal stability of AuNPs.

PMID- 19588957
TI  - Assignment of EC numbers to enzymatic reactions with MOLMAP reaction descriptors
      and random forests.
AB  - The MOLMAP descriptor relies on a Kohonen SOM that defines types of covalent
      bonds on the basis of their physicochemical and topological properties. The
      MOLMAP descriptor of a molecule represents the types of bonds available in that
      molecule. The MOLMAP descriptor of a reaction is defined as the difference
      between the MOLMAPs of the products and the reactants and numerically encodes the
      pattern of changes in bonds during a chemical reaction. In this study, a genome
      scale data set of enzymatic reactions available in the KEGG database was encoded
      by the MOLMAP descriptors and was explored for the assignment of the official EC
      number from the reaction equation with Random Forests as the machine learning
      algorithm. EC numbers were correctly assigned in 95%, 90%, and 85% (for
      independent test sets) at the class, subclass, and subsubclass EC number level,
      respectively, with training sets including one reaction from each available full
      EC number. Increasing differences between training and test sets were explored,
      leading to decreased percentages of correct assignments. The classification of
      reactions only from the main reactants and products was obtained at the class,
      subclass, and subsubclass level with accuracies of 78%, 74%, and 63%,
      respectively.

PMID- 19588958
TI  - New variant of highly symmetric layered perovskite with coordinated NO3(-)
      ligand: hydrothermal synthesis, structure, and characterization of
      Cs2PbCl2(NO3)2.
AB  - A new highly symmetric layered lead chloride material, Cs(2)PbCl(2)(NO(3))(2) has
      been synthesized by a hydrothermal reaction method using Pb(NO(3))(2), CsCl, and
      water at 240 degrees C. The structure has been determined by single-crystal X-ray
      diffraction. Cs(2)PbCl(2)(NO(3))(2) has a novel two-dimensional layered structure
      containing PbO(4)Cl(4) polyhedra and NO(3) trigonal planes.
      Cs(2)PbCl(2)(NO(3))(2) is a novel variant on the layered perovskite theme, of
      which the structure is closely related to the n = 1 layered perovskite families.
      Detailed structural analysis, Infrared and UV-vis diffuse reflectance spectra,
      thermogravimetric analysis, and ion-exchange reactions of Cs(2)PbCl(2)(NO(3))(2)
      are reported. Crystal data: Cs(2)PbCl(2)(NO(3))(2), tetragonal, space group
      I4(1)/amd (No. 141), a = b = 5.6905(6) A, c = 32.946(5) A, V = 1066.9(2) A(3),
      and Z = 4.

PMID- 19588960
TI  - Hard and soft acids and bases: small molecules.
AB  - The operational chemical hardness has been determined for the hydride, chloride,
      and fluoride derivatives of the anionic atomic bases of the second period. Of
      interest is the identification of the structure and associated processes that
      give rise to hard-soft behavior in small molecules. The Pearson Principle of Hard
      and Soft Acids and Bases has been taken to be the defining statement about hard
      soft behavior and as a definition of chemical hardness. Similar to the case for
      atoms, the molecule's responding electrons have been identified as the structure
      giving rise to hard-soft behavior, and a relaxation described by a modified
      Slater model has been identified as the associated process. The responding
      electrons are the molecule's valence electrons that are not undergoing electron
      transfer in an acid-base interaction. However, it has been demonstrated that
      chemical hardness is a local property, and only those responding electrons that
      are associated with the base's binding atom directly impact chemical hardness.

PMID- 19588959
TI  - Theory of free energy and entropy in noncovalent binding.

PMID- 19588961
TI  - N-heterocyclic carbenes in late transition metal catalysis.

PMID- 19588963
TI  - Reduced uranium complexes: synthetic and DFT study of the role of pi ligation in
      the stabilization of uranium species in a formal low-valent state.
AB  - Reaction of UCl(4)(THF)(4) with 1,3-[2,5-(i-Pr)(2)PhNC( horizontal
      lineCH(2))](2)C(6)H(4)Li(2) produced a complex formulated as [{1,3-[2,5-(i
      Pr)(2)PhNC( horizontal lineCH(2))](2)C(6)H(4)}UCl(3)][Li(THF)(4)] (1) that
      exhibits a nonagostic interaction between one of the carbon atoms of the central
      phenyl ring and the U metal center. This interaction leads to significant
      weakening of the corresponding C-H bond, thereby facilitating proton removal in
      consecutive transformations. Attempts to form trivalent uranium derivatives were
      carried out by reacting the same ligand dianion with in situ-prepared "UCl(3)".
      The reaction indeed afforded a trivalent species formulated as {1,3-[2,5-(i
      Pr)(2)PhNC( horizontal lineCH(2))](2)C(6)H(4)}U(mu-Cl)(3)[Li(THF)(2)](2) (2). The
      configuration of the ligand system in this complex is similar to that in 1, with
      the same type of arrangement of the central phenyl ring. Further reduction
      chemistry with a variety of reagents and conditions was examined. Reaction of 1
      with 1 equiv of lithium naphthalenide at 0 degrees C did not afford 2 but instead
      gave a closely related U(III) complex formulated as {1,3-[2,5-(i-Pr)(2)PhNC(
      horizontal lineCH(2))](2)C(6)H(4)}U(THF)(mu-Cl)(2)[Li(Et(2)O)(2)] (3). Both of
      the trivalent complexes 2 and 3 reacted thermally in boiling THF, undergoing
      oxidation of the metal center to afford a new tetravalent compound {1,3-[2,5-(i
      Pr)(2)PhNC( horizontal lineCH(2))](2)C(6)H(3)}U(THF)(mu-Cl)(2)[Li(THF)(2)] (4) in
      which the oxidation of the trivalent center occurred at the expense of the
      central phenyl ring C-H bond. Reaction of 1 with 3 equiv of lithium naphthalenide
      at room temperature afforded {{1,3-[2,5-(i-Pr)(2)PhNC( horizontal
      lineCH(2))](2)C(6)H(3)}U(mu-Cl)(mu-[O(CH(2))(3)CH(2)])[Li(DME)]}[Li(DME)(3)] (5).
      In this species, the tetravalent metal center forms a six-membered metallacycle
      ring with a moiety arising from THF ring opening. Reaction in DME afforded
      reductive cleavage of the solvent accompanied by reoxidation of U to the
      tetravalent state. Reduction of 1 in DME with 2 equiv of potassium naphthalenide
      at room temperature gave a mixture of two compounds having very similar
      structures. The two different species [{1,3-[2,5-(i-Pr)(2)PhNC( horizontal
      lineCH(2))](2)C(6)H(3)}UCl(OCH(3))][Li(DME)(3)] (6a) and [{1,3-[2,5-(i
      Pr)(2)PhNC( horizontal lineCH(2))](2)C(6)H(3)}UCl(2)][Li(DME)(3)] (6b)
      cocrystallized in a ratio very close to 1:1 within the same unit cell. The
      methoxide group was generated from cleavage of the DME solvent. We also attempted
      the reduction of 1 with a different reducing agent such as NaH in DME. After a
      slow reaction, a new species formulated as {1,3-[2,5-(i-Pr)(2)PhNC( horizontal
      lineCH(2))](2)C(6)H(3)}U(mu-OCH(3))(3)(mu,eta(6)-Na)[eta(3)-Na(DME)] (7) was
      isolated in significant yield. Once again, the crystal structure revealed the
      presence of several methoxy groups coordinated to the U center in addition to the
      metalation of the ligand phenyl ring. To minimize solvent cleavage, reduction of
      1 was also carried out at low temperature (-35 degrees C) and with a larger
      amount (4 equiv) of lithium naphthalenide. After suitable workup, the new species
      {[{1,3-[2,5-(i-Pr)(2)PhNC( horizontal lineCH(2))](2)C(6)H(3)}U{1,3-[2,5-(i
      Pr)(2)PhN horizontal lineC(CH(3))](2)C(6)H(4)}][Li(DME)(THF)]}.Et(2)O (8) was
      isolated in significant yield. Even in this case, the uranium atom is surrounded
      by the expected trianionic, ring-metalated ligand. However, a second ligand unit
      surrounds the metal center, being bonded through a part of the pi system.
      Reaction of 1 with excess NaH in toluene proceeded slowly at room temperature,
      affording a significant yield of {[{1,3-[2,5-(i-Pr)(2)PhNC( horizontal
      lineCH(2))](2)C(6)H(3)}U{1,3-[2,5-(i-Pr)(2)PhN horizontal
      lineC(CH(3))](2)C(6)H(4)}{Na(DME)(2)}][Na(DME)(3)]}.(1)/(2)C(7)H(8) (9) after
      crystallization from DME/toluene. Similar to 8, the complex still contains one
      ring-metalated trianionic ligand and one intact ligand that has regained the H
      atoms and restored the two imine functions. Although according to their
      connectivities, complexes 8 and 9 could be assigned with the formal oxidation
      states +2 and +1, respectively, density functional theory calculations clearly
      indicated that these species contain additional spin density on the ligand system
      with the metal center in its more standard trivalent state.

PMID- 19588964
TI  - Reconstruction of Cu(100) electrode surfaces during hydrogen evolution.
AB  - Electrochemical hydrogen evolution on (100)-oriented copper electrodes is shown
      to induce a novel surface reconstruction, which substantially influences the
      rates of this electrochemical reaction. As revealed by in situ video-STM the
      formation of this phase starts with lateral displacements of Cu surface atoms
      from lattice positions, resulting in stripe-like structures, followed by
      expansion of the surface lattice along the stripe direction.

PMID- 19588965
TI  - Selective C-S bond formation via Fe-catalyzed allylic substitution.
AB  - In contrast to the formation of C-O and C-N bonds it was only recently that the
      selective C-S bond formation by means of transition metal complexes moved more
      into the center of research. This is somewhat surprising given the fact that the
      sulfur atom in a functional group can possess different oxygenation levels which
      correspond to different chemical properties and reaction portfolios. Herein we
      wish to communicate a regioselective Fe-catalyzed allylic sulfonation that allows
      for the preparation of various chiral aryl allyl sulfones in good to excellent
      yields.

PMID- 19588962
TI  - Differential binding of Co(II) and Zn(II) to metallo-beta-lactamase Bla2 from
      Bacillus anthracis.
AB  - In an effort to probe the structure, mechanism, and biochemical properties of
      metallo-beta-lactamase Bla2 from Bacillus anthracis, the enzyme was
      overexpressed, purified, and characterized. Metal analyses demonstrated that
      recombinant Bla2 tightly binds 1 equiv of Zn(II). Steady-state kinetic studies
      showed that mono-Zn(II) Bla2 (1Zn-Bla2) is active, while di-Zn(II) Bla2 (ZnZn
      Bla2) was unstable. Catalytically, 1Zn-Bla2 behaves like the related enzymes CcrA
      and L1. In contrast, di-Co(II) Bla2 (CoCo-Bla2) is substantially more active than
      the mono-Co(II) analogue. Rapid kinetics and UV-vis, (1)H NMR, EPR, and EXAFS
      spectroscopic studies show that Co(II) binding to Bla2 is distributed, while
      EXAFS shows that Zn(II) binding is sequential. To our knowledge, this is the
      first documented example of a Zn enzyme that binds Co(II) and Zn(II) via distinct
      mechanisms, underscoring the need to demonstrate transferability when
      extrapolating results on Co(II)-substituted proteins to the native Zn(II)
      containing forms.

PMID- 19588966
TI  - Reduced or diminished stabilization of the telomere G-quadruplex and inhibition
      of telomerase by small chemical ligands under molecular crowding condition.
AB  - Telomere DNA in human cells shortens during each round of DNA replication. In
      cancer cells, telomere shortening is compensated by telomerase or the alternative
      lengthening of telomere (ALT) mechanism to maintain cell division potential. The
      G-rich strand of telomere DNA can fold into a G-quadruplex structure and disrupt
      these two processes. Therefore, stabilization of the G-quadruplex by chemical
      ligands is emerging as a promising anticancer strategy. So far, in vitro studies
      on such ligands are exclusively carried out in dilute solutions. However, the
      intracellular environment is highly crowded with biomolecules. How G-quadruplex
      ligands behave under molecular crowding condition is critical for their in vivo
      anticancer effect. In this work, we studied several ligands for their ability to
      stabilize the telomere G-quadruplex and inhibit telomerase under both dilute and
      crowding conditions. Surprisingly, the ligands became significantly less
      effective or even lost the ability to stabilize the G-quadruplex and inhibit
      telomerase under crowding conditions. Our data attributed this consequence to the
      decreased binding affinity of ligands to the G-quadruplex as a result of reduced
      water activity and increased viscosity of the medium associated with molecular
      crowding. This effect is irrelevant to and overweighs the influences from other
      factors such as the G-quadruplex structure, cation, and ligand species. Our work
      illustrates a possibility that molecular crowding inside cells may reduce or
      limit the potency of ligands although they may be effective in dilute solution,
      thus strongly arguing for the necessity of evaluating ligands under more
      physiologically relevant conditions and designing drugs with this concern in
      mind.

PMID- 19588967
TI  - Mild decarboxylative allylation of coumarins.
AB  - Allyl esters of 3-carboxylcoumarins undergo facile decarboxylative coupling at
      just 25-50 degrees C. This represents the first extension of decarboxylative C-C
      bond-forming reactions to the coupling of aromatics with sp(3)-hybridized
      electrophiles. Finally, the same concept can be applied to the sp(2)-sp(3)
      couplings of pyrones and flavones. Thus, a variety of biologically important
      heteroaromatics can be readily functionalized without the need for strong bases
      or stoichiometric organometallics that are typically required for more standard
      cross-coupling reactions.

PMID- 19588968
TI  - Rapid catalyst-free flame synthesis of dense, aligned alpha-Fe2O3 nanoflake and
      CuO nanoneedle arrays.
AB  - This paper describes a simple and yet rapid flame synthesis method to produce one
      dimensional metal oxide nanostructures by directly oxidizing metals in the
      postflame region of a flat flame. Single and bicrystal alpha-Fe(2)O(3) nanoflakes
      and CuO nanoneedles were grown in the postflame region by a solid diffusion
      mechanism and were aligned perpendicularly to the substrate with a surface
      coverage density of 10 nanostructures per square micrometer. The alpha-Fe(2)O(3)
      nanoflakes reached lengths exceeding 20 microm after only 20 min of growth. This
      rapid growth rate is attributed to a large initial heating rate of the metal
      substrate in the flame and to the presence of water vapor and carbon dioxide in
      the gas phase that together generate thin and porous oxide layers that greatly
      enhance the diffusion of the deficient metal to the nanostructure growth site and
      enable growth at higher temperatures than previously demonstrated.

PMID- 19588971
TI  - Exceptional stability and high hydrogen uptake in hydrogen-bonded metal-organic
      cubes possessing ACO and AST zeolite-like topologies.
AB  - Herein we detail a novel approach for targeting zeolite-like metal-organic
      frameworks (ZMOFs) that utilizes metal-organic cubes, which are regarded as
      double four-membered rings (d4Rs) and are composite building units (BUs) in
      traditional inorganic zeolites. Accordingly, we outline the successful
      implementation of this strategy by reporting two ZMOFs with ACO and AST zeolite
      like topologies, which were constructed from d4R BUs exclusively held together by
      hydrogen bonds. Their porosity was evaluated, delineating high hydrogen uptake
      and exceptional stability for the two hydrogen-bonded materials.

PMID- 19588970
TI  - Synthesis of Cu-doped InP nanocrystals (d-dots) with ZnSe diffusion barrier as
      efficient and color-tunable NIR emitters.
AB  - Efficient Cu-doped InP quantum dots (Cu:InP d-dots) emitters were successfully
      synthesized by epitaxial growth of a ZnSe diffusion barrier for the dopants. The
      Cu dopant emission of the Cu:InP/ZnSe core/shell d-dots covered the important red
      and near-infrared (NIR) window for biomedical applicaitons, from 630 to 1100 nm,
      by varying the size of the InP host nanocrystals. These new d-dots emitters not
      only compensate for the emission wavelength of the existing noncadmium d-dots
      emitters, Cu- and Mn-doped ZnSe d-dots (450-610 nm), but also offer a complete
      series of efficient nanocrystal emitters based on InP nanocrystals. The one-pot
      synthetic scheme for the formation of Cu:InP/ZnSe core/shell d-dots was
      successfully established by systematically studying the doping process, the
      dopant concentration-dependent photophysical properties, and the dopant diffusion
      during shell epitaxy, etc. Complete elimination of InP bandgap emission and
      efficient pure dopant emission (with photoluminescence quantum yield as high as
      between 35-40%) of the core/shell d-dots were achieved by optimizing the final
      doping level and the diffusion barrier thickness.

PMID- 19588969
TI  - Kinetic intermediate reveals staggered pH-dependent transitions along the
      membrane insertion pathway of the diphtheria toxin T-domain.
AB  - The pH-triggered membrane insertion pathway of the T-domain of diphtheria toxin
      was studied using site-selective fluorescence labeling with subsequent
      application of several spectroscopic techniques (e.g., fluorescence correlation
      spectroscopy, FRET, lifetime quenching, and kinetic fluorescence). FCS
      measurements indicate that pH-dependent formation of the membrane-competent form
      depends only slightly on the amount of anionic lipids in the membrane. The
      subsequent transbilayer insertion, however, is strongly favored by anionic
      lipids. Kinetic FRET measurements between the donor-labeled T-domain and acceptor
      labeled lipid vesicles demonstrate rapid membrane association at all pH values
      for which binding occurs. In contrast, the transmembrane insertion kinetics is
      significantly slower and is also both pH- and lipid-dependent. Analysis of
      kinetic behavior of binding and insertion indicates the presence of several
      interfacial intermediates on the insertion pathway of the T-domain, from soluble
      W-state to transmembrane T-state. Intermediate interfacial I-state can be trapped
      in membranes with low content of anionic lipids (10%). In membranes of greater
      anionic lipid content, another pH-dependent transition results in the formation
      of the insertion-competent state and subsequent transmembrane insertion.
      Comparison of the results of various kinetic and equilibrium experiments suggests
      that the pH dependences determining membrane association and transbilayer
      insertion transitions are different but staggered. Anionic lipids not only assist
      in formation of the insertion-competent form but also lower the kinetic barrier
      for the final insertion.

PMID- 19588973
TI  - Macroporous silicon oxycarbide fibers with luffa-like superhydrophobic shells.
AB  - High-surface-area silicon oxycarbide macroporous fibers were fabricated through
      in situ cross-linking of a preceramic precursor without a prepatterned template.
      The unique luffa-like shell combined with intrinsic silicon-containing groups
      accounts for the resultant superhydrophobic property. Meanwhile, the oil-uptake
      capacity of the corresponding fiber mat is significantly improved by the
      capsulated nanoparticles.

PMID- 19588974
TI  - Optical activity and chiral memory of thiol-capped CdTe nanocrystals.
AB  - CdTe nanocrystals (NCs) passivated with chiral ligands d- and l
      cysteinemethylester hydrochloride were prepared and observed to exhibit
      characteristic CD profiles with symmetrical mirror images depending on the
      chirality of the capping ligand. The optical activity of CdTe NCs is shown to
      originate from the distorted CdS shell including chiral capping molecules. The
      chirality of the NC surface is maintained even after ligand exchange with an
      achiral thiol, providing an unprecedented chiral memory effect.

PMID- 19588972
TI  - Gold(I)-catalyzed cascade cyclization of allenyl epoxides.
AB  - Cationic gold(I) phosphite catalysts activate allenes for epoxide cascade
      reactions. The system is tolerant of numerous functional groups (sulfones,
      esters, ethers, sulfonamides) and proceeds at room temperature in
      dichloromethane. The cyclization pathway is sensitive to the substitution pattern
      of the epoxide and the backbone structure of the A-ring. It is capable of
      producing medium-ring ethers, fused 6-5 bicyclic, and linked pyran-furan
      structures. The resulting cycloisomers are reminiscent of structures found in
      numerous polyether natural products.

PMID- 19588975
TI  - Determination by fourier transform Raman spectroscopy of conjugated linoleic acid
      in I2-photoisomerized soybean oil.
AB  - The potential of Fourier transform (FT)-Raman spectroscopy to quantify the total
      conjugated linoleic acid (CLA) content was evaluated to find a technique for the
      routine control of CLA synthesis by chemical procedures. The calibration and
      validation samples were obtained by photoisomerization of linoleic acid contained
      in soybean oil. The catalyst was iodine (I(2)), and the light source was the
      green line (514.5 nm) of an argon ion laser. The criteria to select the best
      partial least-squares (PLS) calibration model were a low standard error of
      prediction (SEP), a high correlation coefficient (R), and the selection of
      relevant variables of the Raman spectrum to reduce spectral interferences. The
      total CLA content of the 22 samples ranged from 0.05 to 3.28% of total lipids.
      The best PLS calibration model was obtained with three optimal factors, a SEP of
      0.22, and a R of 0.97. This calibration model was obtained after baseline
      correction of the CC stretching region (1642-1680 cm(-1)), which contained
      sufficient spectral information for reliable CLA quantification.

PMID- 19588978
TI  - Statistical evaluation of triacylglycerol composition in plant oils based on high
      performance liquid chromatography-atmospheric pressure chemical ionization mass
      spectrometry data.
AB  - The statistical evaluation of triacylglycerol profiles in plant oils based on
      high-performance liquid chromatography mass spectrometry (HPLC/MS) analysis
      enables the differentiation of various plant oils on the basis of the
      multidimensional data matrix. A data set of 93 oil samples from 60 varieties of
      plants composed from 355 triacylglycerols is evaluated using the principal
      component analysis. Analyzed samples are resolved in the principal component
      analysis plot, and similarities among some types of plant oils are visualized by
      the formation of clusters. The authentication of plant oils is tested with model
      samples of olive oil adulterated with sunflower oil at different concentration
      levels. Our HPLC/MS method using the statistical multivariate data analysis of a
      large data matrix enables a clear identification of adulterated olive oils
      already from 1% of added sunflower oil as an adulterant.

PMID- 19588976
TI  - Extending mass spectrometry contribution to therapeutic monoclonal antibody lead
      optimization: characterization of immune complexes using noncovalent ESI-MS.
AB  - Monoclonal antibodies (mAbs) have taken on an increasing importance for the
      treatment of various diseases including cancers, immunological disorders, and
      other pathologies. These large biomolecules display specific structural features,
      which affect their efficiency and need, therefore, to be extensively
      characterized using sensitive and orthogonal analytical techniques. Among them,
      mass spectrometry (MS) has become the method of choice to study mAb amino acid
      sequences as well as their post-translational modifications. In the present work,
      recent noncovalent MS-technologies including automated chip-based
      nanoelectrospray MS and traveling wave ion mobility MS were used for the first
      time to characterize immune complexes involving both murine and humanized mAb 6F4
      directed against human JAM-A, a newly identified antigenic protein (Ag)
      overexpressed in tumor cells. MS-based structural insights evidenced that
      heterogeneous disulfide bridge pairings of recombinant JAM-A alter neither its
      native structure nor mAbs 6F4 recognition properties. Investigations focused on
      mAb:Ag complexes revealed that, similarly to murine mAb, humanized mAb 6F4 binds
      selectively up to four antigen molecules with a similar affinity, confirming in
      this way the reliability of the humanization process. Noncovalent MS appears as
      an additional supporting technique for therapeutic mAbs lead characterization and
      development.

PMID- 19588979
TI  - Quantitative evaluation of metal-molecule contact stability at the single
      molecule level.
AB  - Practical realization of any electronic device requires a quantitative measure of
      their durability for the sake of guaranteeing the reliability. Unfortunately,
      however, there exists no such tool for molecular devices. The present article
      provides a solution to this issue in molecular electronics by reporting an
      experimental demonstration of a quantitative comparison of thermodynamic
      stability of single-molecule junctions consisting of two distinct anchor groups:
      thiol and amine. We report solid evidence that Au-thiol bonds are far more stable
      than Au-amine linkages through exhibiting 2-fold longer natural lifetime of Au
      aminobenzenethiol-Au single-molecule junctions compared to the Au-benzenediamine
      Au counterpart. We also find that a single-molecule device composed of Au-thiol
      links is a factor of 100000 more stable than that configured with Au-amine
      contacts.

PMID- 19588980
TI  - Dealcoholized wines by spinning cone column distillation: phenolic compounds and
      antioxidant activity measured by the 1,1-diphenyl-2-picrylhydrazyl method.
AB  - Spinning cone column (SCC) distillation has been shown to be a commercially
      suitable technique for dealcoholized wine (DW) manufacturing, but there are not
      enough studies about its influence on the DW quality. So, the effect of this
      technique on the antioxidant activity (% of remaining 1,1-diphenyl-2
      picrylhydrazyl radical) and the phenolic compound composition of red, rose, and
      white DW, obtained at pilot plant scale, has been analyzed. Nineteen raw wines
      (RWs) from different grape varieties and five different Spanish viticultural
      regions have been studied before and after dealcoholization. The total phenolic
      content, flavonols, tartaric esters, and anthocyanins, was determined by
      spectrophotometry, while the content of phenolic compounds such as stilbenes
      (trans- and cis-resveratrol), flavonols (rutin, quercetin, and myricetin), flavan
      3-ols [(+)-catechin and (-)-epicatechin], anthocyanins (malvidin 3-glucoside),
      and non-flavonoids (gallic, caffeic, and p-coumaric acids) was determined by high
      performance liquid chromatography (HPLC). The resveratrol contents in red wines
      were between 1.81 and 34.01 mg/L in RWs and between 2.12 and 39.57 mg/L in DWs,
      Merlot being the grape producing the RWs and DWs with higher resveratrol content.
      In general, the percent of remaining DPPH(*) was similar or slightly higher
      (until 5 units of % of remaining DPPH(*)) in DWs versus RWs. This small
      difference may be due to removal of SO2 (that is an antioxidant) from RWs during
      distillation. DWs and RWs show similar contents of the studied phenolic
      compounds, with a tendency, in some cases, to exhibit increases after
      dealcoholization, caused by the concentration effect via removal of the ethanol.
      From this work, we can deduce that SCC distillation is a dealcoholization
      technique minimally destructive with the wine phenolic compounds.

PMID- 19588981
TI  - Electrochemical and electronic structure investigations of the [S3N3]* radical
      and kinetic modeling of the [S4N4]n/[S3N3]n (n = 0, -1) interconversion.
AB  - Voltammetric studies of S(4)N(4) employing both cyclic (CV) and rotating disk
      (RDE) methods in CH(2)Cl(2) at a glassy carbon electrode reveal a one-electron
      reduction at -1.00 V (versus ferrocene/ferrocenium), which produces a second
      redox couple at -0.33 V, confirmed to be the electrochemically generated
      [S(3)N(3)](-) by CV studies on its salts. Diffusion coefficients (CH(2)Cl(2)/0.4
      M [(n)Bu(4)N][PF(6)]) estimated by RDE methods: S(4)N(4), 1.17 x 10(-5) cm(2) s(
      1); [S(3)N(3)](-), 4.00 x 10(-6) cm(2) s(-1). Digital simulations of the CVs
      detected slow rates of electron transfer for both couples and allowed for a
      determination of rate constants for homogeneous chemical reaction steps
      subsequent to electron transfer. The common parameters (k(f1) = 2.0 +/- 0.5 s(
      1), k(s1) = 0.034 +/- 0.004 cm s(-1) for [S(4)N(4)](-/0); k(f2) = 0.4 +/- 0.2 s(
      1), k(s2) = 0.022 +/- 0.005 cm s(-1) for [S(3)N(3)](-/0) at T = 21 +/- 2 degrees
      C) fit well to a "square-scheme" mechanism over the entire range of data with
      first order decay of both redox products. An alternate model could also be fit
      wherein [NS](*) liberated in the first step reacts with formed [S(3)N(3)](*) to
      reproduce S(4)N(4) with an apparent second order rate constant k(f2)' = 1.1 +/-
      0.3 x 10(3) M(-1) s(-1). The crystal structure of [PPN][S(3)N(3)] was determined
      by X-ray crystallography indicating the solvation of the anion by 1 equiv of
      methanol. The generated [S(4)N(4)](-*) radical anion was detected by the
      Simultaneous Electrochemical Electron Paramagnetic Resonance (SEEPR) method to
      give: (a) [(32)S(4)(14)N(4)](-*), 9 lines, a((14)N) = 0.118 mT; (b)
      [(32)S(4)(15)N(4)](-*), 5 lines, a((15)N) = 0.164 mT; (c) [(33)S(4)(14)N(4)](-*),
      estimated a((14)N) = 0.118, a((33)S = 0.2 mT); g = 2.0008(1). Equivalence of
      (33)S hyperfine splittings is consistent with dynamic averaging of the C(2v)
      geometry in solution. High-level electronic structure calculations provide
      evidence for an open-shell doublet triradicaloid character to the ground state
      wave function of [S(3)N(3)](*).

PMID- 19588982
TI  - Deciphering intrinsic deactivation/isomerization routes in a phytochrome
      chromophore model.
AB  - High level ab initio correlated (CASPT2) computations have been used to elucidate
      the details of the photoinduced molecular motion and decay mechanisms of a
      realistic phytochrome chromophore model in vacuo and to explore the reasons
      underneath its photophysical/photochemical properties. Competitive deactivation
      routes emerge that unveil the primary photochemical event and the intrinsic
      photoisomerization ability of this system. The emerged in vacuo based static
      (i.e., nondynamical) reactivity model accounts for the formation of different
      excited state intermediates and suggests a qualitative rationale for the short
      (picosecond) excited state lifetime and ultrafast decay of the emission, its
      small quantum yield, and the multiexponential decay observed in both solvent and
      phytochromes. It is thus tentatively suggested that this is a more general
      deactivation scheme for photoexcited phytochrome chromophores that is independent
      of the surrounding environment. Spectroscopic properties have also been simulated
      in both isolated conditions and the protein that satisfactorily match
      experimental data. For this purpose, preliminary hybrid QM/MM computations at the
      correlated (CASPT2) level have been used in the protein and are reported here for
      the first time.

PMID- 19588984
TI  - Association of a weakly acidic anti-inflammatory drug (ibuprofen) with a
      poly(amidoamine) dendrimer as studied by molecular dynamics simulations.
AB  - In this work, we report results from fully atomistic molecular dynamics
      simulations regarding the associative behavior of a third-generation
      poly(amidoamine) dendrimer with ibuprofen, a weakly acidic nonsteroidal anti
      inflammatory drug, in aqueous solutions and at different pH conditions. Employing
      a combined static and dynamic approach, we describe the specifics of the
      complexation/encapsulation of the drug within the dendritic structure. In
      addition, information regarding the dynamic behavior is provided for the self-
      and the collective motion of the drug molecules. The detail afforded by the
      present molecular-level description of the relevant associative mechanisms (i.e.,
      electrostatic complexation, hydrogen-bonding), provides a deeper insight for the
      interpretation of recent experimental findings regarding the behavior of
      dendrimer/ibuprofen systems in an aqueous environment.

PMID- 19588985
TI  - NanoPen: dynamic, low-power, and light-actuated patterning of nanoparticles.
AB  - We introduce NanoPen, a novel technique for low optical power intensity,
      flexible, real-time reconfigurable, and large-scale light-actuated patterning of
      single or multiple nanoparticles, such as metallic spherical nanocrystals, and
      one-dimensional nanostructures, such as carbon nanotubes. NanoPen is capable of
      dynamically patterning nanoparticles over an area of thousands of square
      micrometers with light intensities <10 W/cm(2) (using a commercial projector)
      within seconds. Various arbitrary nanoparticle patterns and arrays (including a
      10 x 10 array covering a 0.025 mm(2) area) are demonstrated using this
      capability. One application of NanoPen is presented through the creation of
      surface-enhanced Raman spectroscopy hot-spots by patterning gold nanoparticles of
      90 nm diameter with enhancement factors exceeding 10(7) and picomolar
      concentration sensitivities.

PMID- 19588987
TI  - Atom-bond pairwise additive representation for halide-benzene potential energy
      surfaces: an ab initio validation study.
AB  - The detailed knowledge of the basic aspects of molecular interactions and the
      representation of the involved potential energy surface in a proper analytical
      form are of paramount importance either to elucidate the nature of noncovalent
      interactions or to perform meaningful molecular dynamics simulations. To this
      aim, a recently developed semiempirical method, formulated in terms of atom/ion
      molecular bond interactions, has been extended to investigate X(-)-C(6)H(6)
      systems (X = F, Cl, Br, I) and tested against highly correlated MP2 ab initio
      calculations. The role of the various components to the total interaction energy
      was also addressed by comparing the semiempirical contributions to their MP2
      counterparts calculated using the symmetry adapted perturbation theory. The
      overall results, besides providing a more detailed picture of the interaction
      between anions and aromatic systems, pointed out that the current model is able
      to reproduce remarkably well the main features of the potential energy surface
      for the heavier X(-)-C(6)H(6) systems (X = Cl, Br, I), whereas for fluoride
      benzene, the binding energies are underestimated as a consequence of the failure
      of the semiempirical method to describe the electrostatic interaction between a
      diffuse anion and a benzene at short range by means of a simple point charge
      model.

PMID- 19588986
TI  - Measurements of heme relaxation and ligand recombination in strong magnetic
      fields.
AB  - Heme cooling signals and diatomic ligand recombination kinetics are measured in
      strong magnetic fields (up to 10 T). We examined diatomic ligand recombination to
      heme model compounds (NO and CO), myoglobin (NO and O(2)), and horseradish
      peroxidase (NO). No magnetic field induced rate changes in any of the samples
      were observed within the experimental detection limit. However, in the case of CO
      binding to heme in glycerol and O(2) binding to myoglobin, we observe a small
      magnetic field dependent change in the early time amplitude of the optical
      response that is assigned to heme cooling. One possibility, consistent with this
      observation, is that there is a weak magnetic field dependence of the
      nonradiative branching ratio into the vibrationally hot electronic ground state
      during CO photolysis. Ancillary studies of the "spin-forbidden" CO binding
      reaction in a variety of heme compounds in the absence of magnetic field
      demonstrate a surprisingly wide range for the Arrhenius prefactor. We conclude
      that CO binding to heme is not always retarded by unfavorable spin selection
      rules involving a double spin-flip superexchange mechanism. In fact, it appears
      that the small prefactor ( approximately 10(9) s(-1)) found for CO rebinding to
      Mb may be anomalous, rather than the general rule for heme-CO rebinding. These
      results point to unresolved fundamental issues that underlie the theory of heme
      ligand photolysis and rebinding.

PMID- 19588988
TI  - Direct imaging of optical cavity modes in ZnO rods using second harmonic
      generation microscopy.
AB  - Images of second harmonic generation (SHG) in needle-shaped ZnO rods obtained
      from individual structures show areas of enhanced second harmonic intensity along
      the longitudinal axis of the rod that are periodically distributed and
      symmetrically situated relative to the rod midpoint. The spatial modulation is a
      direct consequence of the fundamental optical field coupling into standing wave
      resonator modes of the ZnO structure, leading to an enhanced backscattered second
      harmonic condition that cannot be achieved in bulk ZnO. A more complicated second
      harmonic image is observed when excitation is below the band gap, which is
      attributed to whispering gallery modes. This physical phenomenon, which extends
      beyond just ZnO to many other optical materials, could pave the way to new
      applications that exploit the nonlinear optical properties of individual
      structures.

PMID- 19588990
TI  - Changes in cell wall composition associated to the softening of ripening papaya:
      evidence of extensive solubilization of large molecular mass galactouronides.
AB  - Papaya (Carica papaya) is a climacteric fruit that undergoes dramatic pulp
      softening. Fruits sampled at three different conditions (natural ripening or
      after exposition to ethylene or 1-methylcyclopropene) were used for the isolation
      of cell wall polymers to find changes in their degradation pattern. Polymers were
      separated according to their solubility in water, CDTA, and 4 M alkali, and their
      monosaccharide compositions were determined. Water-soluble polymers were further
      characterized, and their increased yields in control and ethylene-treated fruit,
      in contrast to those that were treated with 1-MCP, indicated a strong association
      between fruit softening and changes in the cell wall water-soluble polysaccharide
      fraction. The results indicate that the extensive softening in the pulp of
      ripening papayas is a consequence of solubilization of large molecular mass
      galacturonans from the pectin fraction of the cell wall. This process seems to be
      dependent on the levels of ethylene, and it is likely that the releasing of
      galacturonan chains results from an endo acting polygalacturonase.

PMID- 19588992
TI  - Nanoferrite embedded magnetocochleate microstructures to encapsulate insulin
      macromolecules.
AB  - A fused lipid microstructure embedded with ferrite nanoparticles, a
      magnetocochleate, was prepared and used to encapsulate insulin by making use of
      the lipid phase transition from the fluidic lamellar phase to the gel phase at pH
      2. The magnetocochleate obtained by tuning the hydrophilic headgroup hydration of
      phosphatidylserine in the presence of ferrite encapsulates a larger amount of
      insulin. Enhanced encapsulation of insulin in between the fused lipid bilayer
      indicates that the magnetocochleate has potential as a delivery vehicle for an
      active pharmaceutical incipient. In particular, protein macromolecules like
      insulin are target incipients, because these fused microstructures protect
      insulin from the action of enzymes and from pH changes, which is necessary to
      maintain its bioactivity. Microscopic and spectroscopic investigations of these
      fused microstructures were done to understand the internal microstructure and
      encapsulation of protein. Freeze fracture transmission electron microscopy
      revealed the gel-like phase of fused lipid bilayers and the presence of ferrite
      in magnetocochleate. Confocal micro-Raman, high performance liquid chromatography
      (HPLC) studies confirmed the presence of ferrite and insulin within the lipid
      microstructures. Differential scanning calorimetry (DSC) and Fourier transform
      infrared resonance (FTIR) studies substantiate the state of lipid in these fused
      microstructures. In vivo subcutaneous activity was studied in a rat model, and
      the positive result obtained there signifies the promising potential of
      magnetocochleates in subcutaneous delivery of macromolecules.

PMID- 19588991
TI  - Fourier transform infrared microspectroscopic analysis of the effects of cereal
      type and variety within a type of grain on structural makeup in relation to rumen
      degradation kinetics.
AB  - The objectives of this study were to use Fourier transform infrared
      microspectroscopy (FTIRM) to determine structural makeup (features) of cereal
      grain endosperm tissue and to reveal and identify differences in protein and
      carbohydrate structural makeup between different cereal types (corn vs barley)
      and between different varieties within a grain (barley CDC Bold, CDC Dolly,
      Harrington, and Valier). Another objective was to investigate how these
      structural features relate to rumen degradation kinetics. The items assessed
      included (1) structural differences in protein amide I to nonstructural
      carbohydrate (NSC, starch) intensity and ratio within cellular dimensions; (2)
      molecular structural differences in the secondary structure profile of protein,
      alpha-helix, beta-sheet, and their ratio; (3) structural differences in NSC to
      amide I ratio profile. From the results, it was observed that (1) comparison
      between grain types [corn (cv. Pioneer 39P78) vs barley (cv. Harrington)] showed
      significant differences in structural makeup in terms of NSC, amide I to NSC
      ratio, and rumen degradation kinetics (degradation ratio, effective degradability
      of dry matter, protein and NSC) (P < 0.05); (2) comparison between varieties
      within a grain (barley varieties) also showed significant differences in
      structural makeup in terms of amide I, NSC, amide I to NSC ratio, alpha-helix and
      beta-sheet protein structures, and rumen degradation kinetics (effective
      degradability of dry matter, protein, and NSC) (P < 0.05); (3) correlation
      analysis showed that the amide I to NSC ratio was strongly correlated with rumen
      degradation kinetics in terms of the degradation rate (R = 0.91, P = 0.086) and
      effective degradability of dry matter (R = 0.93, P = 0.071). The results suggest
      that with the FTIRM technique, the structural makeup differences between cereal
      types and between different varieties within a type of grain could be revealed.
      These structural makeup differences were related to the rate and extent of rumen
      degradation.

PMID- 19588993
TI  - Spin and orbital ground state of Co in cobalt phthalocyanine.
AB  - The 3d orbital ground state of transition-metal ions that are incorporated in a
      molecular matrix determines the total spin of the transition-metal ion as well as
      the spin anisotropy and thus the essential magnetic properties of the
      corresponding molecule. However, there is little known to date on the exact 3d
      ground state of many molecular systems, including quite complex molecular magnets
      as well as relatively simple systems such as, for instance, cobalt phthalocyanine
      (CoPc). For the latter, there are contradictory theoretical predictions with
      respect to the occupation of the various Co 3d electronic levels. We demonstrate
      that polarization-dependent X-ray absorption spectroscopy in combination with a
      simulation of the spectra is able to shed a brighter light on the spin and
      orbital ground state of the transition-metal ion in CoPc. Our results reveal a
      temperature-dependent ground state and emphasize the importance of taking 3d
      correlation effects properly into account.

PMID- 19588996
TI  - Lewis acid catalyzed reaction of methylenecyclopropanes with 1,2-diphenyldiselane
      or 1,2-di-p-tolyldisulfane.
AB  - Catalyzed by Lewis acid, 1,2-diphenyldiselane or 1,2-di-p-tolyldisulfane could
      add to methylenecyclopropanes smoothly. Compared with the reported free radical
      additions, the results were quite different. A four-membered carbon ring was
      constructed to give cyclobutane-1,1-diylbis(phenylselane) derivatives or
      cyclobutane-1,1-diylbis(p-tolylsulfane) derivatives as products, which are useful
      intermediates in organic synthesis.

PMID- 19588995
TI  - Transport-metabolism interplay: LXRalpha-mediated induction of human ABC
      transporter ABCC2 (cMOAT/MRP2) in HepG2 cells.
AB  - Human ATP-binding cassette (ABC) transporter ABCC2 (cMOAT/MRP2) plays a crucial
      role in the hepatobiliary transport of sulfate-, glucuronide-, and glutathione
      conjugated metabolites as well as a variety of amphiphilic organic anions derived
      from hepatic metabolism. Molecular mechanisms underlying the induction of this
      hepatic ABC transporter are of great interest to understand the transport
      metabolism interplay in vivo. In the present study, to gain insight into the
      mechanism of ABCC2 induction, we tested a total of 46 structurally diverse
      compounds, including nuclear receptor ligands, antibiotics, bile salts,
      phytochemicals, and anticancer drugs. Among them, we found that LXRalpha ligands,
      i.e., T0901317, paxilline, and 22(R)-hydroxycholesterol, acted potently to induce
      the expression of ABCC2 at both mRNA and protein levels in human hepatocellular
      carcinoma HepG2 cells. The ABCC2 induction by T0901317 was dose- and time
      dependent, where the induction pattern of ABCC2 was very similar to that of
      ABCG1, one of the target genes of LXRalpha. The ABCC2 induction by T0901317 was
      more strongly elicited when the LXRalpha gene was transiently transfected into
      HepG2 cells. In contrast, ABCC2 induction by T0901317 was attenuated by transient
      transfection of a dominant negative LXRalpha variant, suggesting that LXRalpha is
      involved in ABCC2 induction. Interestingly, RXR, a heterodimer partner of
      LXRalpha, affected the mRNA levels of ABCC2 and ABCG1 differently. ABCC2
      induction by T0901317 was enhanced by RXR siRNA treatment, whereas ABCG1
      induction was suppressed by the same treatment. This is the first report
      demonstrating that LXRalpha is potentially involved in ABCC2 induction.

PMID- 19588994
TI  - Synthesis and in vivo antitumor efficacy of PEGylated poly(l-lysine) dendrimer
      camptothecin conjugates.
AB  - Polymer conjugates of camptothecin (CPT) have been pursued as a solution to the
      difficulties present in treating cancers with CPT and its derivatives. Covalent
      attachment of CPT to a polymer can improve solubility, increase blood circulation
      time, enhance tumor uptake, and significantly improve efficacy of the drug. In
      this report, we describe a novel polymer conjugate of CPT using a core
      functionalized, symmetrically PEGylated poly(l-lysine) (PLL) dendrimer. The
      PEGylated dendrimer consisted of a lysine dendrimer functionalized with aspartic
      acid, which was used as an attachment site for poly(ethylene glycol) (PEG) and
      CPT. The final conjugate had a molecular weight of 40 kDa and was loaded with 4-6
      wt % CPT. Polymer-bound CPT was shown to have a long blood circulation half-life
      of 30.9 +/- 8.8 h and a tumor uptake of 4.2 +/- 2.3% of the injected dose/g of
      tissue, compared to free CPT in which less than 1% was retained in the blood
      after 30 min and had a tumor accumulation of 0.29 +/- 0.04% of the injected
      dose/g of tissue. The PEGylated PLL-CPT showed superior efficacy in murine (C26)
      and human colon carcinoma (HT-29) tumor models when compared with no treatment or
      treatment with irinotecan. In the C26 tumor model, treatment resulted in
      significantly prolonged survival (P < 0.05) for all mice treated with a single
      injection of PEGylated PLL-CPT. In the HT-29 tumor model, all mice treated with
      multiple injections of a low dose survived to the end of the study, with three
      mice of eight surviving tumor-free.

PMID- 19588997
TI  - Dihydroxylation of 4-substituted 1,2-dioxines: a concise route to branched
      erythro sugars.
AB  - The synthesis of 2-C-branched erythritol derivatives, including the plant sugar
      (+/-)-2-C-methylerythritol 2, was achieved through a dihydroxylation/reduction
      sequence on a series of 4-substituted 1,2-dioxines 3. The asymmetric
      dihydroxylation of 1,2-dioxines was examined, providing access to optically
      enriched dihydroxy 1,2-dioxanes 4. The synthesized 1,2-dioxanes were converted to
      other erythro sugar analogues and tetrahydrofurans through controlled cleavage of
      the endoperoxide linkage.

PMID- 19588998
TI  - Direct N-carbamoylation of 3-monosubstituted oxindoles with alkyl imidazole
      carboxylates.
AB  - Regioselective N-carbamoylation of oxindoles was achieved through the use of
      imidazole carboxylate reagents. This reaction provides ready access to N
      carbamoyl-3-monosubstituted oxindoles.

PMID- 19589000
TI  - Reproductive effects and bioaccumulation of chlordane in Daphnia magna.
AB  - Acute and chronic toxicity of high-grade chlordane (98%) and bioaccumulation were
      investigated in Daphnia magna at water soluble concentrations obtained without
      cosolvent. The measured effective concentrations immobilizing 50% of the
      microcrustacea (95% confidence interval) were 22.6 (19.7-26.1) microg/L at 24 h
      and 13.4 (11.3-15.8) microg/L at 48 h. This indicated an increase of chlordane
      toxicity with time of exposure as confirmed in chronic studies. After 21 d of
      exposure, significant effects on survival were recorded at a chlordane
      concentration greater than 2.9 microg/L, whereas reproduction (number of
      offspring per adult, brood size) and length of adults decreased at 0.7 microg/L
      or more in a concentration- and time-dependent manner. The production of male
      offspring and developmental abnormalities, consisting of underdeveloped second
      antennae and shell spines in live neonates, were recorded. The chlordane
      concentration tested with no significant adverse effect (NOEC) on reproduction of
      daphnids after 21 d compared with controls was 0.18 microg/L. The bioaccumulation
      factor of chlordane by daphnids exposed at a level of concentration close to the
      21-d NOEC reached 10,600, wet weight, and 244,000, dry weight, after 40 d. The
      trans-chlordane bioaccumulated to a greater extent than the cis isomer in
      daphnids, whereas the cis isomer was predominant in the test medium. The results
      suggest a crucial role of the invertebrates in transfer of chlordane in aquatic
      food webs and can be used to derive a freshwater guideline for environmental
      protection accounting for bioaccumulation.

PMID- 19588999
TI  - A comparison of nanoparticle and fine particle uptake by Daphnia magna.
AB  - The use of nanoparticles in various applications is steadily on the rise, with
      use in a range of applications, including printer toner, sunscreen, medical
      imaging, and enhanced drug delivery. While research on human effects via, for
      example, inhalation is relatively well developed, the environmental assessment of
      nanoparticles is in its infancy. In the present study, we assessed the uptake and
      quantitative accumulation, as well as the depuration, of a model nanoparticle, a
      20-nm fluorescent carboxylated polystyrene bead, in the aquatic invertebrate
      Daphnia magna and compared it to a larger, 1,000-nm particle. Using confocal
      microscopy, rapid accumulation in the gastrointestinal tract was observed within
      an hour of exposure to both particle sizes in both adults and neonates.
      Fluorescence could also be observed in the oil storage droplets, suggesting that
      both particle sizes have crossed the gut's epithelial barrier. Quantification of
      fluorescence of both sizes of particles showed that although uptake of the 20-nm
      particles was lower in terms of mass it was equal to or greater than 1000-nm
      particle uptake when expressed as surface area or particle number. Depuration was
      relatively rapid for the 1000-nm beads, decreasing by more than 90% over 4 h. In
      contrast, depuration of the 20-nm beads was less extensive, reaching 40% over 4
      h. Transmission electron microscopy confirmed uptake of 1,000-nm beads, but
      uptake of 20-nm beads was inconclusive since similar-sized inclusions could be
      observed in control treatments.

PMID- 19589001
TI  - Contamination and screening level toxicity of sediments from remediated and
      unremediated wetlands near Sydney, Australia.
AB  - The present study assessed contamination and toxicity of sediments from seven
      remediated and remnant wetland sites within Sydney Olympic Park, Australia, and
      four unremediated sites adjacent to its boundary using chemical analysis and a
      luminescent bacterial biosensor assay (Escherichia coli). Concentrations of
      metals (Pb, Cr, Cu, Ni, Zn, Cd, and As) and persistent organic chemicals (DDT and
      its metabolites, dichlorodiphenyldichloroethane and
      dichlorodiphenyldichloroethylene; polycyclic aromatic hydrocarbons;
      polychlorinated biphenyls; and polychlorinated dibenzo-p-dioxins and
      dibenzofurans) in sediments and their pore-water samples were determined. Zinc
      concentrations were the highest of the metals in the sediments (84-618 mg/kg),
      and at eight sites, metal concentrations in sediments exceeded the Australian
      ecological trigger values for Pb, Zn, and Ni. Concentrations of organic
      contaminants in the sediments exceeded the trigger values at all 11 sites for
      DDTs, at 6 sites for polycyclic aromatic hydrocarbons, and 5 sites for
      polychlorinated biphenyls. Sediment samples from the four unremediated sites
      outside the Sydney Olympic Park had dioxin concentrations greater than 200 pg
      (toxic equivalency per gram). The same four sites were identified as contaminated
      in pore-water toxicity tests with the luminescent biosensor, generally consistent
      with the bioavailable fractions of the contaminants (pore-water and Tenax
      extraction data), as well as dioxin levels, in the sediments. Preliminary
      toxicity identification and evaluation tests of the pore water from the four
      sites outside the park demonstrated that organic contaminants were the main cause
      of toxicity to E. coli, with no evidence that metals contributed to the toxicity
      of the pore water.

PMID- 19589002
TI  - Cerebellar loss and brain-stem atrophy associated with neonatal alloimmune
      thrombocytopenia in a discordant twin.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is due to an immune-mediated maternal
      fetal platelet antigen incompatibility. Central nervous system abnormalities have
      been reported in infants with NAIT and include intracranial hemorrhage,
      ventriculomegaly, porencephalic cysts, neuronal migrational disorders, and,
      rarely, cerebellar lesions. We present the clinical and neuropathological
      findings from a case of a 3-day-old diamniotic/dichorionic female twin with known
      bilateral ventriculomegaly born prematurely at 33-1/7 weeks in gestational age.
      The pregnancy was further complicated by discordant intrauterine growth,
      intraventricular hemorrhage in the co-twin, and NAIT. At birth, the infant was
      noted to have diffuse body ecchymoses and petechiae and arthrogryposis. She
      subsequently developed multisystem organ failure and disseminated intravascular
      coagulopathy and died on the 3rd day of life. Neuropathological findings at
      autopsy included a posterior fossa cyst with no gross anatomic evidence of a
      cerebellum, atrophic pons and medulla with prominent pyramidal tracts and absent
      olivary nuclei, thinned corpus callosum, and symmetrical dilation of bilateral
      lateral ventricles. Microscopic examination confirmed the gross findings and
      revealed no histological evidence of cerebellar tissue, absence of superior and
      inferior cerebellar peduncles, and acute and chronic germinal matrix hemorrhages.
      Immunohistochemical studies revealed a focus of reactive gliosis at the base of
      the posterior fossa cyst with no evidence of cerebellar Purkinje or granule
      cells. To our knowledge, this is the 1st report with well-characterized
      neuropathological examination detailing complete cerebellar loss and brain-stem
      atrophy in a neonate with NAIT.

PMID- 19589006
TI  - A multiattribute decision model for bipolar disorder: identification of preferred
      mood-stabilizing medications.
AB  - OBJECTIVE: To develop a multiattribute decision model (MADM) to aid in the
      selection of preferred medications for the treatment of bipolar disorder. STUDY
      DESIGN: Data were obtained via a self-administered online survey among
      psychiatric pharmacist specialists. These survey data were used to construct a
      MADM based on multiattribute utility technology. METHODS: Anticonvulsant mood
      stabilizers, atypical antipsychotics, olanzapine-fluoxetine combination, and
      lithium carbonate were evaluated using a MADM. Attributes included in the model
      were effectiveness, safety and tolerability, cost, monitoring burden, and dosing
      frequency. A survey instrument was developed to score the relative importance of
      each attribute and the factor scores for each medication. Four iterations of the
      model were performed to ascertain the medication with the highest total utility
      score when the effectiveness factors were weighted to consider the following:
      overall effectiveness, effectiveness in acute mania, effectiveness in acute
      bipolar depression, and effectiveness in maintenance treatment. Sensitivity
      analyses were performed to evaluate the stability of the MADM results. RESULTS:
      When overall effectiveness, effectiveness in acute mania, or effectiveness in
      maintenance treatment was considered, lithium carbonate had the highest total
      utility score. When effectiveness in acute bipolar depression was considered,
      lamotrigine had the highest total utility score. When considering only atypical
      antipsychotics, aripiprazole was associated with the highest total utility score
      for all iterations of the MADM. CONCLUSION: The use of a MADM may be a beneficial
      tool to assist in making formulary or preferred therapeutic agent decisions.

PMID- 19589007
TI  - Impact of workplace health services on adherence to chronic medications.
AB  - OBJECTIVE: To test the association between integrated workplace health and
      pharmacy care and medication adherence. STUDY DESIGN: Adherence rates for
      commonly used chronic disease medications were compared in a retrospective, non
      case-controlled study of 4476 workplace-treated patients versus 13,134 community
      treated patients. METHODS: Pharmacy claims data were used to compute the
      medication possession ratio for patients who received care in different settings
      for 20 therapeutic classes. Statistical tests for assessing between-group
      differences were performed, controlling for differences due to age, sex, number
      of chronic conditions, number of medication therapeutic classes, and patient out
      of-pocket cost per therapy day. Results were reported for overall adherence as
      well as adherence for patients on new medications. RESULTS: Significant
      differences were found between workplace-treated patients and community-treated
      patients. Workplace-treated patients had overall adherence rates that were 9.72%
      higher than those of community-treated patients. This pattern was repeated with
      an overall adherence rate that was 9.52% higher for workplace-treated patients
      when prescriptions were limited to medication new starts. CONCLUSIONS: Integrated
      workplace primary care and pharmacy services are one way to increase medication
      adherence. These services have the potential not only to save healthcare dollars,
      but also improve the lives of chronically ill patients.

PMID- 19589008
TI  - Lipid profile changes associated with changing available formulary statins:
      removing higher potency agents.
AB  - OBJECTIVE: To review the fasting lipid panel changes that occurred after removing
      higher potency statins from a prescription formulary. STUDY DESIGN: Retrospective
      chart review. METHODS: Researchers compiled data for patients in a medical clinic
      receiving pharmacy benefits from a particular managed care plan. Patients
      enrolled in the benefits program at least between June 2006 and June 2007 were
      evaluated for atorvastatin use before January 1, 2007. After January 1, patients
      on atorvastatin were prescribed new statins according to the program's preferred
      drug list. Patients treated with atorvastatin were reviewed for fasting lipid
      panel results while on atorvastatin; these results then were compared with
      fasting lipid panels after the formulary change took place. Total cholesterol,
      low-density lipoprotein, high-density lipoprotein, and triglyceride values were
      examined for changes. Appropriateness of the replacement statin also was
      evaluated using statin equivalency charts. RESULTS: Values for total cholesterol,
      low-density lipoprotein, and triglycerides were not significantly different from
      baseline to follow-up. High-density lipoprotein values did significantly increase
      over the study period. Only 34% of statin prescriptions were considered
      appropriately converted to equipotent or higher potency doses. The mean time to
      documentation of statin conversion was 2.9 months. CONCLUSIONS: Removing higher
      potency statins from the formulary did not ignificantly change a population's
      fasting lipid panel except for a significant increase in high-density
      lipoprotein. Although multiple factors may have contributed to this effect, the
      results of this investigation suggest that changing formulary statins will not
      alter the surrogate lipoprotein markers associated with poor cardiovascular
      outcomes.

PMID- 19589010
TI  - Automated messaging to improve compliance with diabetes test monitoring.
AB  - OBJECTIVES: To evaluate the use of automated systems to prompt patients with
      diabetes mellitus to obtain overdue laboratory tests for its effectiveness in
      promoting test compliance and to compare letters, telephone messages, and
      combinations. STUDY DESIGN: Randomized controlled trial. METHODS: All subjects (N
      = 13,057) were adult members of Southern California Kaiser Permanente with
      diabetes and with no record of glycosylated hemoglobin, low-density lipoprotein
      cholesterol, and urinary microalbumin tests in more than 1 year. The
      effectiveness of automated telephone calls and letters was compared versus a no
      contact control group using the following 5 intervention groups: letter, call,
      letter that is followed by a call 4 weeks later, call that is followed by a
      letter 4 weeks later, and letter-call-letter combination. Messages were in
      English and in Spanish. Adherence to all testing was compared at 8 weeks and 12
      weeks after initial contact using chi(2) test and logistic regression analysis.
      RESULTS: The proportions of each study group compliant with all tests were 18% to
      19% among controls, 21% for a letter or a call, 25% for a letter-call or call
      letter, and 26% for a letter-call-letter; letter-call and call-letter were
      significantly different versus controls (P <.001), and letter-call-letter was not
      significantly different versus letter-call. Older age was associated with
      compliance (P <.001). CONCLUSIONS: The pairing of automated letters and telephone
      calls in any order was more effective than any single intervention in promoting
      compliance with diabetes monitoring tests. The relative cost of the letter-call
      and call-letter approaches to outreach should be considered to determine which is
      preferred in any given situation.

PMID- 19589011
TI  - Medicaid beneficiaries with congestive heart failure: association of medication
      adherence with healthcare use and costs.
AB  - OBJECTIVES: To examine the association of medication adherence with healthcare
      use and costs among Medicaid beneficiaries with congestive heart failure (CHF),
      to investigate whether the association was a graded one, and to estimate the
      potential savings due to improved adherence. STUDY DESIGN: Using Medicare and
      Medicaid data for 4 states, adherence was estimated using the medication
      possession ratio (MPR). METHODS: Multivariate logistic and 2-part general linear
      models were estimated to study the primary objectives. The MPR was specified in
      multiple ways to examine its association with healthcare use and costs. RESULTS:
      Adherent beneficiaries were less likely to have a hospitalization (0.4 percentage
      points), had fewer hospitalizations (13%), had in excess of 2 fewer inpatient
      days (25%), were less likely to have an emergency department (ED) visit (3%), and
      had fewer ED visits (10%) than nonadherent beneficiaries. Total healthcare costs
      were $5910 (23%) less per year for adherent beneficiaries compared with
      nonadherent beneficiaries. The relationship between medication adherence and
      healthcare costs was graded. For example, beneficiaries with adherence rates of
      95% or higher had about 15% lower healthcare costs than those with adherence
      rates between 80% and less than 95% ($17,665 vs $20,747, P <.01). The
      relationship between adherence and total healthcare costs was even more stark
      when the most adherent beneficiaries were segmented into finer subgroups.
      CONCLUSIONS: Healthcare costs among Medicaid beneficiaries with CHF would be
      lower if more patients were adherent to prescribed medication regimens.
      Researchers should reconsider whether a binary threshold for adherence is
      sufficient to examine the association of adherence with outcomes and healthcare
      costs.

PMID- 19589009
TI  - Adherence to osteoporosis medications after patient and physician brief
      education: post hoc analysis of a randomized controlled trial.
AB  - OBJECTIVE: To examine whether adherence to osteoporosis medications can be
      improved by educational interventions targeted at primary care physicians (PCPs)
      and patients. STUDY DESIGN: Post hoc analysis of data collected as part of a
      prospective randomized controlled trial to improve initiation of osteoporosis
      management such as bone mineral density testing or osteoporosis drug initiation.
      METHODS: The trial was conducted among patients at risk for osteoporosis enrolled
      in Horizon Blue Cross Blue Shield of New Jersey. For a 3-month period, randomly
      selected PCPs and their patients received education about osteoporosis diagnosis
      and treatment. The PCPs received face-to-face education by trained pharmacists,
      while patients received letters and automated telephone calls. The control group
      received no education. We assessed medication adherence during 10 months
      following the start of the intervention using the medication possession ratio
      (MPR), the ratio of available medication to the total number of days studied.
      RESULTS: These analyses included 1867 patients (972 randomized to the
      intervention group and 875 to the control group) and their 436 PCPs. During 10
      months following the intervention, the median MPRs were 74% (interquartile range
      [IQR], 19%-93%) for the intervention group and 73% (IQR, 0%-93%) for the control
      group (P = .18). The median times until medication discontinuation after the
      intervention were 85 days (IQR, 58-174 days) for the intervention group and 79
      days (IQR, 31-158 days) for the control group. CONCLUSION: The educational
      intervention did not significantly improve medication compliance or persistence
      with osteoporosis drugs.

PMID- 19589012
TI  - Medication adherence and use of generic drug therapies.
AB  - OBJECTIVE: To assess whether lower copayments charged for generic drugs explain
      the improved drug adherence associated with use of generics. METHODS: We analyzed
      2001-2004 healthcare claims data from 45 large employers. Study subjects were age
      > or = 18 years, had 1 or more of 5 study conditions (hypercholesterolemia,
      hypertension, hypothyroidism, seizure disorders, type 2 diabetes), and new use of
      generic-only or brand-only drug therapy for that condition. We measured adherence
      as the medication possession ratio (MPR), and adequate adherence as MPR > or =
      80%. Logistic regressions were conducted to assess adequate adherence, adjusting
      for copayments. RESULTS: We identified 327,629 new users of drug therapy. The
      proportion starting generic therapies ranged from 9% (hypothyroidism) to 45%
      (hypertension). After 1 year, 66.2% of individuals with hypothyroidism achieved
      an MPR > or = 80% compared with 53.4% with hypertension, 53.2% with
      hypercholesterolemia, 52.0% with diabetes, and 42.2% with seizure disorders.
      Generics were associated with greater adherence than brands in patients with
      hypercholesterolemia or diabetes (P <.05). Lower adherence was seen in patients
      with hypertension or hypothyroidism (P <.05). There was no difference in seizure
      disorders. The likelihood of achieving an MPR =80% with $0 copayments compared
      with $1 to $9 ranged from an adjusted odds ratio (AOR) of 1.32 for seizure
      disorders (95% confidence interval [CI] = 1.41, 1.43) to an AOR of 1.45 for
      hypothyroidism (95% CI = 1.43, 1.48). CONCLUSION: Generic prescribing was
      associated with modestly improved adherence in 2 of 5 study conditions.
      Copayments of $0 were associated with improved adherence across all conditions.

PMID- 19589013
TI  - Measuring concurrent adherence to multiple related medications.
AB  - OBJECTIVES: To propose standardized methods for measuring concurrent adherence to
      multiple related medications and to apply these definitions to a cohort of
      patients with diabetes mellitus. STUDY DESIGN: Retrospective cohort study of 7567
      subjects with diabetes prescribed 2 or more classes of oral hypoglycemic agents
      in 2005. METHODS: For each medication class, adherence for each patient was
      estimated using prescription-based and interval-based measures of proportion of
      days covered (PDC) from cohort entry until December 31, 2006. Concurrent
      adherence was calculated by applying these 2 measures in the following 3 ways:
      (1) the mean of each patient's average PDC, (2) the proportion of days during
      which patients had at least 1 of their medications available to them, and (3) the
      proportion of patients with a PDC of at least 80% for all medication classes.
      Because patients taking multiple related medications have distinct patterns of
      use, the analysis was repeated after classifying patients into mutually exclusive
      groups. RESULTS: Concurrent medication adherence ranged from 35% to 95% depending
      on the definition applied. Interval-based measures provide lower estimates than
      prescription-based techniques. Definitions that require the use of at least 1
      drug class categorize virtually all patients as adherent. Requiring patients to
      have a PDC of at least 80% for each of their drugs results in only 30% to 40% of
      patients being defined as adherent. The variability in adherence is greatest for
      patients whose treatment regimen changed the most during follow-up. CONCLUSIONS:
      The variability in adherence estimates derived from different definitions may
      substantially impact qualitative conclusions about concurrent adherence to
      related medications. Because the measures we propose have different underlying
      assumptions, the choice of technique should depend on why adherence is being
      evaluated.

PMID- 19589014
TI  - Human Biology. Editorial.

PMID- 19589015
TI  - The most widely publicized gender problem in human genetics.
AB  - In two-child families containing at least one boy, the expected probability that
      such a family has two boys is 1/3, provided that the boy/girl (B/G) ratio is 1.0
      and the population to which they belong has a binomial distribution of BB, (BG +
      GB), and GG families. It is commonly known that in most human populations the sex
      ratio at birth (i.e., the ratio of the number of boys to the number of girls) is
      greater than 1.0. Teachers and textbook writers seldom discuss the more realistic
      expected distributions in populations where the sex ratio is greater than 1.0. We
      present data from two federal surveys with sex ratios greater than 1.0 and find
      that the observed proportions of two boys in families of size 2 with at least one
      boy range from 0.3335 to 0.3941. It has been reported in the literature that the
      probability (p) of a male birth is subject to both within-sibship variation
      (Poisson variation), for which our data are suggestive, and possibly also between
      sibship variation (Lexis variation). These deviations (biases) from the
      assumptions of a simple binomial distribution are involved in the calculation of
      values of p and standard 95% confidence intervals, thereby foiling attempts to
      make reliable statistical inferences from the data. Analysis of the data is also
      complicated by family planning that falsifies the assumption of randomness in the
      binomial gender distribution model. Families of size 2 (and their sex
      composition) are often discussed in a wider context. Overpopulation in some parts
      of the world has caused mass starvation and threatens to do the same worldwide
      unless the birth rate drops to agriculturally sustainable levels. Even if every
      woman of fertile age has only two children on average from now on, the world's
      population is predicted to continue growing toward 9 billion people by 2050.
      Other sociological problems are bound to follow. Although the birth rate in China
      has recently dropped, the average age of the population has risen, so that by
      2035 it is projected that for each person over age 65 there will be just three
      working-age people. Furthermore, China's one-child policy has already led to a
      sex imbalance where there is a large excess of men for whom marriage and
      parentage is denied.

PMID- 19589016
TI  - Variation of the probability of a male birth within and between sibships.
AB  - Stansfield and Carlton [Human Biology 79:255-260 (2007)] reported that the
      distributions of the combinations of the sexes in human sibships are binomial.
      They inferred that the probabilities of male births are equal and independent
      within and across all sibships. Here I argue that their argument is both invalid
      and false. Contrary to their inference, a binomial distribution may result when
      equal and counterbalancing measures of Poisson and Lexis variation are
      simultaneously present. These conditions are approximately met with respect to
      human births.

PMID- 19589017
TI  - Medical genetic polymorphisms as markers of evolutionary forces within the human
      genome: hypotheses focusing on natural selection in the Basque population.
AB  - Natural selection, drift, and gene flow are the three major evolutionary forces
      at the origin of genetic diversity among human populations. To further explore
      these mechanisms, we present an innovative approach using various medical genetic
      markers and focusing on the Basque population. From this study we can confirm the
      important role of drift in this endogamous human group and can report some
      disorders related to founder effects. Most important, the peculiar distribution
      of various polymorphisms, such as blood group O, factor V Leiden, DF508, C282Y,
      and CCR5 D32 mutations, which are implicated in resistance to infection,
      hemostasis, or iron conservation, could be interpreted as an adaptive profile.
      Multidisciplinary data have shown that the Neolithic period arrived significantly
      later in this southwestern corner of Europe. We hypothesize that the long-lasting
      Paleolithic mode of life, especially regarding nutrition and microbial exposure,
      was at the origin of this selective pressure within this population of ancient
      local ancestry. This approach could open new avenues in the field of population
      genetics.

PMID- 19589018
TI  - Mitochondrial DNA sequence variation in the Boyko, Hutsul, and Lemko populations
      of the Carpathian highlands.
AB  - Genetic studies of the distribution of mitochondrial DNA (mtDNA) haplogroups in
      human populations residing within the Carpathian Mountain range have been scarce.
      We present an analysis of mtDNA haplogroup composition of the Boykos, Hutsuls,
      and Lemkos, three population groups of the Carpathian highlands. In our study
      Hutsuls had the highest frequency of subhaplogroup H1 in central and eastern
      Europe. Lemkos shared the highest frequency of haplogroup I ever reported and the
      highest frequency of haplogroup M(*) in the region. MtDNA haplogroup frequencies
      in Boykos were different from most modern European populations. We interpreted
      these unique mtDNA frequencies to be evidence of diverse and dynamic population
      histories in the Carpathian highland region.

PMID- 19589019
TI  - Incidence and distribution of Native American mtDNA haplogroups in central
      Argentina.
AB  - We report the incidence and distribution of Native American mtDNA haplogroups in
      nine villages across the Sierras Centrales archeological area, located in central
      Argentina. The aims of the study were (1) to investigate the relative incidence
      of native maternal lineages, (2) to determine whether or not the homogeneous
      pattern observed in a previous study persists at this larger scale, and (3) to
      ascertain the genetic affinities between the studied population and other native
      populations of the Southern Cone of South America. Of the 310 individuals from
      whom DNA was extracted, 249 (80.3%) were assigned to one of the founding native
      American haplogroups. This finding confirms the persistence at high prevalence of
      native maternal lineages in the rural populations of central Argentina. The
      haplogroup distribution is homogeneous in the population samples from Cordoba
      province, with haplogroups C and D always found at the highest frequencies. The
      sample from San Luis province, Tilisarao, presents a different genetic pattern,
      with haplogroups A and B being the most frequent. Principal components analysis
      and SAMOVA at the regional level show that the Cordoba, Patagonia, and Tierra del
      Fuego populations cluster together, which suggests a common origin.

PMID- 19589020
TI  - Autosomal STR analyses in native Amazonian tribes suggest a population structure
      driven by isolation by distance.
AB  - Eleven short tandem repeat loci (CSF1PO, D3S1358, D5S818, D7S820, D8S1179,
      D13S317, D16S539, D18S51, D21S11, TH01, and TPOX) were investigated in 232
      individuals from 6 Amazonian native tribes (Tiriyo, Waiapi, Zoe, Urubu-Kaapor,
      Awa-Guaja, and Parakana). We added the new data to a database that included five
      previously typed native populations from the same area (Wai Wai, Gaviao, Zoro,
      Surui, and Xavante). The results presented here concern this new data set, which
      accounts for 526 individuals in total. We tested whether major geographic or
      linguistic barriers to gene flow exist among such human groups and tried to find
      a possible anthropological or ethnological explanation for such patterns. We
      measured the average heterozygosity (H) and the number of alleles (N(A) ) and
      found that both are lower than values observed in populations of different ethnic
      backgrounds, such as European or African descendants. Despite such a result, we
      found high between-population variation; lower H and/or N(A) values were obtained
      from four isolated tribes that came into contact with external nonnative
      populations in recent times (1921-1989). By applying analysis of molecular
      variance, generalized hierarchical modeling, and the Structure Bayesian analysis,
      we were not able to detect any significant geographic or linguistic barrier to
      gene flow. Geographic autocorrelation analysis suggests that the genetic
      structure of native Amazonian tribes is better explained by isolation by distance
      because the level of genetic similarity decreases according to linear geographic
      distance, reaching null or negative values at a scale of 300 km.

PMID- 19589021
TI  - Mechanisms and microevolutionary consequences of social homogamy in a 19th
      century Italian community.
AB  - Abstract Choosing a spouse has always been an event subjected to strong social
      control. Consideration of socioprofessional elements is therefore necessary for
      an in-depth understanding of the microevolutionary consequences of marriage. Thus
      in this paper I explore the extent and causes of reproduction isolation between
      different socioprofessional groups of a 19th-century Italian community,
      Casalguidi. Various features of mate choice pattern were investigated by means of
      individual-level data. The results show that Casalguidi was a community with
      strong socioeconomic internal boundaries, in which social belonging mattered much
      more than geographic provenience. The bourgeoisie showed such a high degree of
      social homogamy that it was almost reproductively isolated. Much more openness
      and less isolation was found between the two categories of farm laborers and
      sharecroppers, and day laborers.

PMID- 19589023
TI  - Robotic and open radical prostatectomy: is there reason to be receptive to change
      now and in the future?

PMID- 19589022
TI  - The sex composition of two-children families: heterogeneity and selection for the
      third child: comment on Stansfield and Carlton (2009).

PMID- 19589024
TI  - Predictive modeling in cancer: where systems biology meets the stock market.

PMID- 19589026
TI  - Azacitidine for the treatment of myelodysplastic syndrome.
AB  - The myelodysplastic syndromes (MDS) encompass a heterogeneous group of malignant
      hematologic disorders characterized by ineffective hematopoiesis, peripheral
      cytopenias, frequent karyotypic abnormalities and significant risk for
      transformation to acute myeloid leukemia (AML). The prognosis of patients with
      intermediate- or high-risk MDS is very poor. This is due to the fact that
      standard therapeutic options are largely palliative. Neither autologous stem cell
      transplantation (SCT) nor chemotherapeutic regimens have been shown to prolong
      survival in patients with MDS. Allogeneic SCT, while potentially curative, is
      only available to a selected group of patients and is associated with high
      morbidity and mortality in elderly patients, which constitute the majority of
      patients with MDS. Hypermethylation of tumor-suppressor genes has been invoked as
      an important pathogenetic mechanism in MDS. The pyrimidine nucleoside analog
      azacitidine, which inhibits DNA methyltransferases, has recently become the first
      therapeutic to prolong survival in patients with MDS, thus changing the natural
      history of these malignancies. The activity of azacitidine in MDS has spurred the
      development of combinations of this agent with other epigenetic modifiers for the
      treatment of MDS and AML.

PMID- 19589027
TI  - Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior
      to autologous transplantation in multiple myeloma.
AB  - Doxorubicin and pegylated liposomal doxorubicin are key compounds of several
      induction regimens used prior to autologous stem cell transplantation in patients
      with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone
      (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or
      PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is
      to summarize the more recent data available on the efficacy of these combinations
      and to discuss their role as part of initial therapy.

PMID- 19589029
TI  - Cervical cancer therapy: current, future and anti-angiogensis targeted treatment.
AB  - While the incidence of cervical cancer has declined significantly in the USA,
      ethnic disparities remain in terms of increased mortality and morbidity.
      Furthermore, this disease continues to be a significant burden on developing
      countries, with cervical cancer currently ranked as the second most common cause
      of cancer-related morbidity and the third most common cause of mortality
      worldwide. Treatment of cervical cancer has typically been viewed as surgical
      with possible adjuvant therapy versus initial radiotherapy and platinum-based
      chemotherapy. Prognosis and therapy for patients with recurrent disease is
      dependent upon the site of recurrence and ability to pursue curative therapy.
      This article will review the management of cervical cancer, including studies
      that have evaluated the treatment of distant metastasis or recurrent disease, as
      well as discussing the importance of angiogenesis and the use of therapies
      targeted against this phenomenon.

PMID- 19589028
TI  - Kinase Inhibitor 4 Minisymposium summary.
AB  - In recent years no cancer therapeutic class has undergone more prolific or
      successful drug development efforts than the kinase inhibitors. The robust
      research interest is evident in the number of kinase inhibitor presentations at
      the American Association for Cancer Research Annual Meeting held in Denver (CO,
      USA) 18-22 April 2009. Presentation highlights from the Kinase Inhibitor 4
      Minisymposium include the identification of FGF receptor genetic alterations that
      correlate with sensitivity to the kinase inhibitor TKI258; evaluation of activity
      of mitotic kinase inhibitors GSK461364A and AZD1152 in breast and small-cell lung
      cancer and the identification of new inhibitors to PI3K/AKT/mTOR pathway.

PMID- 19589030
TI  - Systemic therapy for recurrent endometrial cancer: a review of North American
      trials.
AB  - While early-stage endometrial cancer is highly curable after hysterectomy for the
      majority of patients afflicted with this disease, recurrent and metastatic
      endometrial cancer continues to pose a significant challenge. The median survival
      of women with advanced or recurrent uterine cancer on most recent clinical trials
      is only approximately 1 year. This review will discuss the developments of
      systemic therapy in recurrent endometrial cancer, focusing on North American
      trials, in particular those documenting recent progress in new drug developments,
      as well as the future of individualized treatment regimens.

PMID- 19589031
TI  - Role of cytoreductive surgery in recurrent ovarian cancer.
AB  - Cytoreductive surgery is well established in patients with primary ovarian
      cancer. The benefit of surgery in patients with recurrent ovarian cancer remains
      a controversial matter. There is a large heterogeneity in surgical results
      published in the literature, possibly caused by infrastructure, surgeons'
      philosophy and belief in adding various surgical skills. This might also be a
      result of different preoperative selection procedures. Further questions to be
      addressed are the definition of surgical end points and whether there are
      predictive factors for a successful surgery. The surgical end point in recurrent
      ovarian cancer should be complete resection. Predictive factors could help
      identify patients in whom complete resection is possible.

PMID- 19589032
TI  - Imaging modalities for prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed malignancy in the Western male
      population and the associated socioeconomic impact on healthcare is of great
      concern. Since the early 1990s, MRI has evolved into an important diagnostic
      imaging modality for prostate cancer patients. In this review, the applications
      of diagnostic imaging modalities in prostate cancer, such as transrectal
      ultrasound, computed tomography and MRI are described. The clinical value of
      these techniques in prostate cancer detection, localization, characterization,
      staging and active surveillance are discussed.

PMID- 19589033
TI  - Additional therapy for high-risk prostate cancer treated with surgery: what is
      the evidence?
AB  - Single-modality approaches to the treatment of high-risk prostate cancer, whether
      radical prostatectomy or external-beam radiotherapy, have yielded disappointing
      results. Treatment intensification has, thus, been the subject of considerable
      research activity in recent years. This review will discuss the evidence for
      neoadjuvant and adjuvant treatment approaches when surgery is chosen as the
      definitive therapy for high-risk prostate cancer. Particular emphasis will be
      placed on the randomized trials, both completed and in progress. Trials
      investigating adjuvant radiotherapy, androgen-deprivation therapy and
      chemotherapy will each be discussed in turn. Among these, only adjuvant
      radiotherapy has been shown to prolong survival after surgery, and the recently
      published evidence for this benefit will be discussed in detail.

PMID- 19589034
TI  - Novel treatment methods for localized prostate cancer: hypofractionated robotic
      radiation therapy and adjuvant chemotherapy.
AB  - The standard localized therapies for prostate cancer include external-beam
      radiation therapy, brachytherapy and radical prostatectomy. There are several
      novel approaches in development aimed at improving local disease control and
      survival, and reducing post-treatment complications. In low-to-intermediate-risk
      patients, new radiation approaches are being explored to include hypofractionated
      robotic radiation therapy. For high-risk patients, the focus is on multimodality
      approaches, especially the addition of chemotherapy. Recent developments in
      radiation therapy and adjuvant chemotherapy are the focus of this review.

PMID- 19589035
TI  - Bilateral Wilms' tumor: the need to improve outcomes.
AB  - Wilms tumor (WT) is the most common primary malignant renal tumor of childhood,
      accounting for 6% of all pediatric tumors, and represents one of the great
      success stories in pediatric cancer therapy. The paradigm for the treatment of a
      child with WT has evolved from a primary goal of survival alone to a risk-based
      approach. Unfortunately, despite 35 years of clinical trials by cooperative
      groups, bilateral WT (BWT) patients have not been formally studied. The most
      recent survival, rated for patients treated on National WT Study-5 with BWT, was
      61-80.8% with favorable histology and 43.8% for a child with anaplastic or
      unfavorable histology. This article reviews outcomes and surgical considerations
      in the treatment of patients with synchronous BWT and proposes possible future
      directions in the treatment.

PMID- 19589036
TI  - Obesity and renal cell carcinoma: epidemiology, underlying mechanisms and
      management considerations.
AB  - The incidence of both renal cell carcinoma (RCC) and obesity are steadily rising
      in Western societies. Recent studies have established that obesity is a
      significant risk factor for the development of several malignancies, including
      RCC. However, the mechanisms underlying this relationship remain to be fully
      elucidated. We review herein the epidemiological links between obesity and RCC,
      the potential mechanisms by which obesity can influence RCC development and
      progression, and the special considerations related to the treatment of obese
      patients with RCC.

PMID- 19589037
TI  - Minimally invasive surgery for renal cell carcinoma.
AB  - The oncologic principles of the surgical management of renal cell carcinoma (RCC)
      have remained essentially the same since first proposed by Robson in 1963. RCC
      remains a chemo- and radiation-resistant tumor; hence, surgical treatment is
      still the mainstay of curative therapy. Extirpative management of RCC via open
      radical nephrectomy (and later open partial nephrectomy) has been the standard of
      care for decades. With the advent of laparoscopic surgery and its intense
      application in urology in the early 1990s, a paradigm shift to minimally invasive
      renal surgery was initiated and has spurred an array of technologies, methods and
      procedures. Guidelines on the proper selection of patients and treatment
      modalities have been developed and established, allowing patients to benefit from
      better oncologic efficacy and reduced morbidity, and requiring urologic surgeons
      to master minimally invasive procedures alongside the techniques of open surgery.
      This review focuses on the minimally invasive management of RCC, discussing the
      advantages and disadvantages of laparoscopy, partial nephrectomy, probe ablation
      and newer treatment modalities. In order to provide material for this review, a
      search of the MEDLINE database was performed through January 2009 using the
      National Center for Biotechnology Information PubMed internet site to review the
      world literature regarding the minimally invasive treatment of RCC.

PMID- 19589038
TI  - Biological mechanisms of bevacizumab-associated adverse events.
AB  - The perception that inhibition of cancer-associated angiogenesis would be an
      effective treatment strategy was based on the fundamental difference in cell
      cycle activity between neoplastic and normal endothelial cells. Selective
      targeting of tumor vessels could have additional benefits, such as circumventing
      development of acquired resistance to these types of agents, overcoming intrinsic
      tumor resistance, exhibiting broad anti-tumor activity and decreasing normal
      tissue toxicity. Successful translation of anti-angiogenic therapy into the
      clinical setting was achieved only 5 years ago with the approval of bevacizumab
      for metastatic colorectal cancer. Although the benefits demonstrated in clinical
      trials led to the approval of bevacizumab for treatment of colorectal, lung and
      breast cancers, and most recently glioblastoma, a number of serious soft-tissue
      and vascular toxicities have also been observed in patients receiving this anti
      angiogenic agent. This review assesses the relationship between inhibition of
      VEGF and toxicity, and proposes the pathogenic mechanisms that lead to the
      adverse events.

PMID- 19589040
TI  - Developmental engineering: a new paradigm for the design and manufacturing of
      cell-based products. Part II: from genes to networks: tissue engineering from the
      viewpoint of systems biology and network science.
AB  - The field of tissue engineering is moving toward a new concept of "in vitro
      biomimetics of in vivo tissue development." In Part I of this series, we proposed
      a theoretical framework integrating the concepts of developmental biology with
      those of process design to provide the rules for the design of biomimetic
      processes. We named this methodology "developmental engineering" to emphasize
      that it is not the tissue but the process of in vitro tissue development that has
      to be engineered. To formulate the process design rules in a rigorous way that
      will allow a computational design, we should refer to mathematical methods to
      model the biological process taking place in vitro. Tissue functions cannot be
      attributed to individual molecules but rather to complex interactions between the
      numerous components of a cell and interactions between cells in a tissue that
      form a network. For tissue engineering to advance to the level of a
      technologically driven discipline amenable to well-established principles of
      process engineering, a scientifically rigorous formulation is needed of the
      general design rules so that the behavior of networks of genes, proteins, or
      cells that govern the unfolding of developmental processes could be related to
      the design parameters. Now that sufficient experimental data exist to construct
      plausible mathematical models of many biological control circuits, explicit
      hypotheses can be evaluated using computational approaches to facilitate process
      design. Recent progress in systems biology has shown that the empirical concepts
      of developmental biology that we used in Part I to extract the rules of
      biomimetic process design can be expressed in rigorous mathematical terms. This
      allows the accurate characterization of manufacturing processes in tissue
      engineering as well as the properties of the artificial tissues themselves. In
      addition, network science has recently shown that the behavior of biological
      networks strongly depends on their topology and has developed the necessary
      concepts and methods to describe it, allowing therefore a deeper understanding of
      the behavior of networks during biomimetic processes. These advances thus open
      the door to a transition for tissue engineering from a substantially empirical
      endeavor to a technology-based discipline comparable to other branches of
      engineering.

PMID- 19589041
TI  - Suicide in war veterans: the role of comorbidity of PTSD and depression.

PMID- 19589043
TI  - Levodopa/carbidopa/entacapone in Parkinson's disease.
AB  - Levodopa is the most efficacious agent for the treatment of motor features of
      Parkinson's disease but its chronic use is associated with the development of
      motor complications. Mounting evidence indicates the short half-life of levodopa
      and resultant pulsatile stimulation of striatal dopamine receptors leads to
      wearing off, motor fluctuations and dyskinesias. Longer acting dopaminergic
      agents, such as dopamine agonists, are less likely to cause motor fluctuations
      and dyskinesias but are not as efficacious for control of motor symptoms.
      Therefore, there is interest in exploring ways to deliver levodopa in a more
      continuous fashion, in an effort to maintain benefit through the day and reduce
      the development of motor fluctuations and dyskinesias. A dopa decarboxylase
      inhibitor (DDCI), such as carbidopa or benserazide, is administered with levodopa
      to attenuate its peripheral conversion to dopamine, reduce nausea and increase
      central bioavailability. When levodopa is administered with a DDCI, its main
      route of peripheral metabolism is via catechol-O-methyl transferase (COMT). A
      COMT inhibitor can be added to the combination of levodopa and a DDCI to further
      extend the levodopa peripheral half-life and increase central bioavailability.
      Stalevo is a combination tablet comprised of levodopa, carbidopa, and the COMT
      inhibitor entacapone. It is available in fixed-dose combinations of
      levodopa/carbidopa/entacapone, 50/12.5/200, 75/18.75/200, 100/25/200,
      125/31.25/200, 150/37.5/200 and 200/50/200 mg. Stalevo is currently approved for
      use in Parkinson's disease patients with end-of-dose wearing off.

PMID- 19589044
TI  - 6th Global College of Neuroprotection and Neuroregeneration, annual meeting.
AB  - The 6th Global College of Neuroprotection and Neuroregeneration (GCNN) and 5th
      Society for Study on Neuroplasticity and Neuroregeneration (SSNN) conference was
      held jointly in the Hilton Hotel, Vienna, Austria, 1-4 March 2009. This was the
      second annual joint conference of the two societies and it was highly successful
      from a scientific point of view, as it saw a gathering of the top basic and
      clinical scientists whose research is currently at the cutting edge of
      neuroscience. This conference saw 86 invited lectures from carefully selected
      leading scientists from around the world, along with 56 posters of young
      scientists researching of a focal theme. Over the 3 days, in 32 sessions, new
      developments in neuroprotection and new ways to enhance neuroregeneration were
      discussed intensively among more than 600 delegates. In addition, approximately
      40 representatives of drug companies, five representatives from scientific
      publishers and 14 representatives from scientific instruments and supplies
      related industries also actively participated in this huge neuroscience event.
      The GCNN and SSNN conference achieved a new milestone in scientific success in
      Vienna and established an excellent new working collaboration among the
      participants in a pleasant, enriched environment with several social gatherings.

PMID- 19589045
TI  - Corpus callosum abnormalities in pediatric bipolar disorder.
AB  - The corpus callosum (CC) is a midline white matter brain region that is important
      in interhemispheric communication and coordination. CC abnormalities are
      associated with a variety of psychiatric conditions, including increased
      vulnerability for psychotic illness, stressful early-life experiences, marijuana
      use, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder,
      borderline personality disorder, dementia, schizophrenia and bipolar disorder. CC
      abnormalities in bipolar disorder have been identified in both pediatric and
      adult populations. In adults, a consistent finding has been a reduction in CC
      size, as well as abnormal axonal orientation or structure. Axonal abnormalities
      have also been noted in pediatric populations, but overall CC size reductions
      have not thus far been demonstrated. Furthermore, there are unique gender
      differences in the expression of CC abnormalities in pediatric populations,
      possibly related to androgen changes during puberty. The protean number of
      conditions in which the CC is involved is reflective of its central role in
      normal brain function and its potential as an early marker of neuropathology in
      psychiatric illness. Specifically, in bipolar disorder it has the potential to be
      useful as an early preclinical marker of disease or disease risk.

PMID- 19589046
TI  - Clinical implications of a staging model for bipolar disorders.
AB  - A model of staging in the field of bipolar disorder (BD) should offer a means for
      clinicians to predict response to treatment and more general outcome measures,
      such as the level of functioning and autonomy. The present staging model
      emphasizes the assessment of patients in the interepisodic period and includes:
      latent phase: individuals who present mood and anxiety symptoms and increased
      risk for developing threshold BD; Stage I--patients with BD who present well
      established periods of euthymia and absence of overt psychiatric morbidity
      between episodes; Stage II--patients who present rapid cycling or current axis I
      or II comorbidities; Stage III--patients who present a clinically relevant
      pattern of cognitive and functioning deterioration, as well as altered
      biomarkers; and Stage IV--patients who are unable to live autonomously and
      present altered brain scans and biomarkers. Such a model implies a longitudinal
      appraisal of clinical variables, as well as assessment of neurocognition and
      biomarkers in the interepisodic period. Staging facilitates understanding of the
      mechanisms underlying progression of the disorder, assists in treatment planning
      and prognosis and, finally, underscores the imperative for early intervention.

PMID- 19589047
TI  - Estrogen, stress and the brain: progress toward unraveling gender discrepancies
      in major depressive disorder.
AB  - Women are twice as likely as men to develop major depressive disorder (MDD) and,
      while the neurobiological factors underlying this discrepancy are yet to be
      identified, estrogen almost certainly plays a role. MDD can be precipitated or
      exacerbated by exposure to stress and there is substantial evidence to suggest
      that estrogen can interact with stress systems to produce unique stress effects
      in females. This review integrates current research in animal models regarding
      estrogen-stress interactions in three areas of the brain known to be relevant to
      MDD: the hippocampus, the amygdala and the prefrontal cortex. The results from
      these studies are discussed in the context of MDD, and their implications for
      future treatment of MDD in women are explored.

PMID- 19589050
TI  - Hypothalamic-pituitary-adrenocortical system dysregulation and new treatment
      strategies in depression.
AB  - According to the corticoid receptor hypothesis of depression, hyperactivity of
      the hypothalamic-pituitary-adrenocortical (HPA) system is one of the major
      pathophysiological factors for the development of depression and opens a broad
      range of new antidepressant treatment options that are related to direct
      interventions in HPA system regulation in depressed patients. These new therapy
      strategies include inhibition of hypothalamic corticotropin-releasing hormone
      (CRH) release, antagonism at CRH1 receptors, antagonism at vasopressin V1b
      receptors, inhibition of cortisol synthesis, antiglucocorticoid treatment with
      dehydroepiandrosterone and treatment with glucocorticoid receptor antagonists.
      Although preclinical data support the view that CRH1 receptor antagonists are
      useful in the treatment of depression, currently no controlled studies are
      available that demonstrate clinical efficacy in depressed patients. The use of
      the antiglucocorticoid neuroactive steroid dehydroepiandrosterone, the cortisol
      synthesis inhibitor metyrapone and the glucocorticoid receptor antagonist
      mifepristone in depression has been demonstrated in some small, double-blind,
      placebo-controlled studies. However, three recently completed Phase III trials
      failed to significantly separate mifepristone from placebo in depression. Thus,
      it is unclear at present to what extent new, clinically effective antidepressant
      therapies can be developed based on the corticoid receptor hypothesis of
      depression.

PMID- 19589049
TI  - Improving adherence in mood disorders: the struggle against relapse, recurrence
      and suicide risk.
AB  - Medication nonadherence is a major obstacle to translating treatment efficacy
      from research settings into effectiveness in clinical practice for patients with
      affective disorders. Adherence to beneficial drug therapy is associated with
      lower mortality compared with poor adherence. Reduced adherence is associated
      with increased suicide risk, especially when lithium is discontinued. The aim of
      this paper is to review the prevalence, predictors and methods for improving
      medication adherence in unipolar and bipolar affective disorders. Studies were
      identified through Medline and PsycInfo searches of English language publications
      between 1976 and 2009. This was supplemented by a hand search and the inclusion
      of selected descriptive articles on good clinical practice. Estimates of
      medication nonadherence for unipolar and bipolar disorders range from 10 to 60%
      (median: 40%). This prevalence has not changed significantly with the
      introduction of new medications. There is evidence that attitudes and beliefs are
      at least as important as side effects in predicting adherence. The limited number
      of empirical studies on reducing nonadherence indicate that, if recognized, the
      problem may be overcome. Clinical data highlight the importance of extended
      courses of medication in improving the long-term prognosis of patients with
      affective disorders.

PMID- 19589051
TI  - sigma-1 receptors in major depression and anxiety.
AB  - Major depression and anxiety are two of the major psychiatric disorders that have
      some overlapping pathophysiologies, the most significant being the dysfunction in
      the monoaminergic, GABAergic and glutamatergic systems. A large number of drugs
      that alter these neurotransmitter levels/systems are effective in the treatment
      of major depression and anxiety. However, full remission of the clinical symptoms
      has not been achieved, perhaps owing to the complex pathophysiology of the
      diseases. Thus, the search for newer targets and target-specific drugs continues.
      Recently, the role of sigma-receptors, particularly the sigma-1 receptor subtype,
      has been identified as a target for the pathophysiology of neuropsychiatric
      disorders, and sigma-1 receptor modulators are considered to be the drugs of the
      future for the treatment of major depression and anxiety. The present review
      attempts to discuss the role of sigma-1 receptors in the pathophysiology of major
      depression and anxiety and also tries to position the use of its receptor
      modulators in the treatment of these two major disorders. The role of sigma-1
      receptors in the mechanism of antidepressant action of venlafaxine, bupropion,
      neurosteroids and one of the herbal antidepressants, berberine, is reviewed.
      Although, sigma-1 receptor modulators may be future therapeutic options, either
      as individual agents or adjuvants in the treatment of mental disorders, the topic
      needs further preclinical and clinical exploration.

PMID- 19589052
TI  - Lack of awareness of illness in schizophrenia: conceptualizations, correlates and
      treatment approaches.
AB  - Many individuals with schizophrenia are unaware of the symptoms and consequences
      of their illness. Unawareness of schizophrenia is linked to poorer adherence to
      treatment and is a risk factor for a range of poorer outcomes. Paradoxically, the
      achievement of awareness may lead to depression, low self-esteem and possibly a
      higher risk of suicide. To explore these issues, this article reviews emerging
      literature on the correlates of unawareness of illness in schizophrenia,
      describes advances in how to address unawareness of illness in a treatment
      setting and discusses newly developing ways of conceptualizing insight. A plan
      for further research is presented, along with an outline for the development of
      methodologies to assess awareness of illness as a narrative phenomenon, which
      calls on a range of neurocognitive and metacognitive capacities, and which must
      deal with the social stigma linked with mental illness.

PMID- 19589048
TI  - Strategies to enhance the therapeutic efficacy of antidepressants: targeting
      residual symptoms.
AB  - Major depressive disorder (MDD) is an illness of great morbidity that affects
      many people across the world. The current goal for treatment of MDD is to achieve
      remission (i.e., no depressive symptoms). However, despite scientific advances in
      the treatment for MDD, antidepressants as first-line agents yield only modest
      remission rates. In fact, a recent study indicated that only one out of three
      subjects who received a standard, first-line antidepressant attained remission.
      Not achieving remission from depressive symptoms increases the risk of a more
      chronic and debilitating course of illness with frequent recurrences. Although a
      number of reasons contribute to these modest outcomes, the presence of residual
      symptoms is a major problem. Residual symptoms are defined as symptoms that
      linger despite an adequate dose and duration of an antidepressant medication.
      This article reviews the prevalence and clinical impact of common residual
      symptoms and discusses the utility of aggressively addressing residual symptoms
      to enhance the efficacy of antidepressant medications.

PMID- 19589053
TI  - Olanzapine dosing above the licensed range is more efficacious than lower doses:
      fact or fiction?
AB  - A substantial number of patients with schizophrenia or bipolar disorder receive
      olanzapine in amounts that are greater than what is recommended in the product
      labeling approved by drug regulatory agencies. The purpose of this review is to
      describe the evidence supporting the use of olanzapine in excess of 20 mg/day.
      PubMed was queried using the keywords 'olanzapine' and 'dose' or 'dosing' for all
      English-language articles published between 1990 and December 2008, inclusive of
      articles that describe utilization of olanzapine at doses in excess of 20 mg/day.
      Also queried was clinicaltrials.gov for studies involving 'olanzapine'. Efficacy
      and safety data were extracted from case reports, case series, observational
      studies and double-blind, randomized clinical trials. We found that the use of
      olanzapine at doses greater than 20 mg/day appears to be increasing. Among
      patients hospitalized for intermediate and long-term care in New York State
      psychiatric centers in the period from 1997 to 2003, the average dose of
      olanzapine increased from 17.4 to 22.5 mg/day. The percentage of patients
      receiving olanzapine at a dose exceeding 20 mg/day increased from 16.2 to over
      50% from 1997 to 2006. Case reports of patients receiving doses up to 60 mg/day
      describe a favorable benefit-risk ratio. Double-blind clinical trials that have
      examined doses of olanzapine greater than 20 mg/day are limited in number, but
      suggest that these doses may be helpful in selected patients who are treatment
      resistant, have high levels of psychopathology or who are acutely agitated. This
      must be balanced by an increased risk of weight gain and elevated prolactin that
      was observed among those receiving 40 mg/day in a large randomized clinical trial
      comparing doses of 40 versus 20 versus 10 mg/day. In conclusion, dosing of
      olanzapine in clinical practice is higher than what has been established in the
      registration program for schizophrenia or bipolar disorder. This is somewhat
      supported by double-blind, controlled clinical trial evidence, but only for
      selected patients with severe and/or persistent symptoms.

PMID- 19589054
TI  - Glial cells in schizophrenia: pathophysiological significance and possible
      consequences for therapy.
AB  - In the last 10 years, structural, molecular and functional changes in glial cells
      have become a major focus of interest in the search for the neurobiological
      foundations of schizophrenia. While neuronal degeneration, as seen in typical
      degenerative brain diseases, cannot be found in post-mortem brains of psychotic
      disorders called 'schizophrenia', many studies show abnormalities in the
      connecting elements between the nerve cell bodies (synapses, dendrites and axons)
      and in all three types of glial cells. There is accumulating evidence of reduced
      numbers of oligodendrocytes and altered gene expression of myelin/oligodendrocyte
      related genes that might explain white matter abnormalities and disturbed inter-
      and intra-hemispheric connectivity, which have frequently been described in
      schizophrenia. Earlier reports of increased astrocyte densities as a sign of
      gliosis could not be confirmed by later studies; however, the expression of
      several astrocyte-related genes is abnormal. Since astrocytes play a key role in
      the synaptic metabolism of glutamate and monamines, astrocyte dysfunction may
      well be related to the current transmitter theories of schizophrenia. Results in
      increased densities of microglial cells, which act as the main cells for immune
      defence in the brain, are more controversial. There are, however, higher
      microglial cell numbers in psychotic patients dying from suicide, and several
      studies reported altered expression of microglia-related surface markers in
      schizophrenia, suggesting that immunological/inflammatory factors may be relevant
      for the pathophysiology of psychosis. Searches for future therapeutic options
      should aim at compensating disturbed functions of oligodendrocytes, astrocytes
      and microglial cells, by which at least some aspects of the pathophysiology of
      the very inhomogeneous clinical syndrome of schizophrenia might be explained.

PMID- 19589055
TI  - The serotonin 5-HT6 receptor: a viable drug target for treating cognitive
      deficits in Alzheimer's disease.
AB  - The serotonin 6 receptor is attracting attention as an etiological contributor in
      cognition deficits in diseases such as Alzheimer's disease, anxiety/depression
      and schizophrenia. In this review, we discuss the role of this recently
      discovered G protein-coupled receptor in cognition and memory, particularly in
      Alzheimer's disease. A surge in publications that describe the development of
      ligands for this receptor have recently come to light, underscoring the emerging
      interest in this receptor as a drug target. We also explore the current status of
      structure-activity relationship studies that have focused on the design of novel
      antagonists for the serotonin 6 receptor.

PMID- 19589056
TI  - The psychological management of facial transplantation.
AB  - Facial transplantation is a major advance in reconstructive surgery, providing
      enormous potential benefit in terms of improved function and cosmesis. Managing
      the challenges it brings depends on understanding both technical and
      psychological issues. Research on the psychological aspects of organ
      transplantation is a starting point; however, issues of altered appearance and
      identity, adjustment to change, the management of suboptimal adherence to
      immunosuppression, and how we present and understand risk, particularly related
      to immunosuppression and rejection, must all be addressed before the procedure
      becomes a clinical option. This review addresses the psychological issues
      highlighted in the Royal College of Surgeons Working Party Report on facial
      transplantation, describing how these have been addressed in the development of a
      clinical program.

PMID- 19589059
TI  - Factors associated with rabid animals since the introduction of raccoon rabies
      variant in Massachusetts, 1992-2007.
AB  - Rabies virus has been identified in 26 animal species since the introduction of
      the raccoon rabies variant (RRV) into the Commonwealth of Massachusetts in 1992.
      This study used data from 47,162 testable specimens, including 4538 (9.62%) rabid
      animals, to produce a multi-categorical logistic regression model to identify
      factors associated with a positive rabies laboratory test. The model was adjusted
      by the animal type and animal species, using the least tested and the least found
      rabid animal species pooled as a reference group. The c-statistic for the final
      model was 0.94, and a receiver operator characteristic curve plot shows the
      increased sensitivity and the decreased false-positive proportion of the model.
      Introduction of RRV into the county where the animal was found (OR = 17.3), not
      up-to-date on vaccination (OR = 3.88), exposure of multiple humans, or pets, or
      human and pet (OR = 1.88), reason for rabies testing (using human exposure only
      as the reference group, the odds ratio for both human and animal exposure is
      2.14; for pet/companion exposure only is 2.96; and for undefined reasons/sick
      animal is 1.49), reported syndromes/observation of aggression (OR = 4.13), ataxia
      (OR = 1.36), disorientation (OR = 1.67), paralysis ( OR = 1.37), and the presence
      of unexplained wounds (OR = 1.27) were all significantly associated with a
      positive rabies testing result at the alpha = 0.05 level.

PMID- 19589060
TI  - Blood-feeding behavior of Aedes albopictus, a vector of Chikungunya on La
      Reunion.
AB  - Chikungunya virus (CHIKV) has long been considered to be transmitted to humans by
      the human-biting mosquito Aedes aegypti, especially in Africa. However, the
      recent outbreak of CHIKV involved another vector, Aedes albopictus, and
      serological data in the literature suggest that several species of domestic or
      human-related vertebrates can be contaminated by this virus. However, the role of
      Ae. albopictus mosquitoes as potential enzootic vectors for CHIKV has not yet
      been evaluated. Here we investigate Ae. albopictus feeding and resting behaviors
      in an area where a CHIKV epidemic recently occurred, which means deciphering host
      seeking and feeding behaviors on several vertebrate species, measuring
      endophagous/exophagous (activity), endophilic/exophilic (resting) behaviors and
      its diel (24 h, day/night) biting activity. Ae. albopictus was found to have
      bimodal daily feeding activities and was found to have exophagic (89%) and
      exophilic (87%) behaviors. Ae. albopictus showed an opportunistic feeding
      behavior on a wide range of hosts (from cold-blooded to warm-blooded animals),
      supporting that it can be implicated in various vertebrate-virus pathosystems.
      However, with equal availability of one of the four vertebrate hosts (calf,
      chicken, dog, and goat) proposed against human, Ae. albopictus significantly
      preferred human, supporting earlier data about its high degree of anthropophily.
      Multiple blood feeding was also reported in every combination (animal/human)
      offered to Ae. albopictus, enlightening the higher risks to spread an arbovirus
      to human population because of interrupted feeding. Such catholic behavior
      suggests that Ae. albopictus may act as a bridge vector for zoonotic viruses.
      Further epidemiological implications of this issue are discussed.

PMID- 19589058
TI  - The effects of West Nile virus on the reproductive success and overwinter
      survival of eastern bluebirds in Alabama.
AB  - We tested for negative effects of West Nile virus (WNV) on a breeding population
      of eastern bluebirds in Alabama by comparing fecundity and reproductive success
      in years before and after the arrival of WNV and by comparing fecundity,
      reproductive success, and overwinter survival of seropositive and seronegative
      individuals within the same population in the same years. We found that female
      bluebirds were more likely to be seropositive than male bluebirds. Age and
      individual condition did not affect likelihood of being seropositive. Being
      seropositive for WNV was not associated with any negative effects on reproduction
      or survival. However, female fecundity was higher in years after WNV compared to
      years before the arrival of WNV. The reproductive success of males who tested
      positive for WNV exposure was higher than that of males that were seronegative.
      Overall, we found no negative effects on reproduction or survival after exposure
      to WNV.

PMID- 19589061
TI  - Applying the theory of island biogeography to emerging pathogens: toward
      predicting the sources of future emerging zoonotic and vector-borne diseases.
AB  - Abstract Emerging infectious diseases are recognized as increasing threats to
      public and animal health, global economy, and social and political stability.
      Climate change, environmental changes, changes in human demographics and
      behaviors, and the rise of global trade and travel are most-often-cited drivers
      for the emergence of infectious diseases in human and animal populations (Schrag
      and Wiener 1995 , Daszak et al. 2001 , Dobson and Foufopoulos 2001 , May et al.
      2001 , Taylor et al. 2001 , Antia et al. 2003 , IOM 2003 , Kuiken et al. 2003 ,
      Weiss and McMichael 2004 , Wolfe et al. 2005 , Woolhouse and Gowtage-Sequeria
      2005 , Chomel et al. 2007 , Woolhouse and Gaunt 2007 , Jones et al. 2008 ).
      Emerging pathogens are more likely to be zoonotic or vector-borne with a broad
      host range (Daszak et al. 2000 , Taylor et al. 2001 , Woolhouse and Gowtage
      Sequeria 2005 , Jones et al. 2008 ). Emerging pathogens are also more frequently
      RNA viruses (Woolhouse and Gowtage-Sequeria 2005 ), which may better adapt to and
      establish in novel host species (Antia et al. 2003 , Andre and Day 2005 ,
      Woolhouse et al. 2005 ). Determining the factors driving disease emergence
      eventually aims at assisting the prediction of the future emergence of infectious
      diseases. However, because of the multifactorial nature of the drivers involved
      (IOM 2003 ), our ability to predict which pathogens may arise in human or animal
      populations in the future remains limited (WHO/FAO/OIE 2004 ). In particular, the
      ability to identify the animal reservoirs where the greatest risks to human
      health will originate was deemed improbable (WHO/FAO/OIE 2004 ). Applying the
      theory of island biogeography (MacArthur and Wilson 1967 ) to emerging pathogens
      identifies (i) interactions between recipient host species and species sources of
      pathogens (including vector species), (ii) interactions within species sources of
      pathogens, and (iii) interactions within recipient host species, as mechanisms
      directly driving disease emergence. Most identified drivers for disease emergence
      correspond to changes in one or more of these three sets of interactions.
      Importantly, applying the theory of island biogeography to emerging pathogens
      assists in predicting from which animal species future zoonotic and vector-borne
      pathogens will most probably emerge. Identifying known and unknown pathogens such
      species harbor may bring us one step forward toward predicting which pathogen
      will next emerge in human populations.

PMID- 19589062
TI  - Appendicitis associated with Taenia species: cause or coincidental?
AB  - A 23-year-old woman from Ethiopia presented with acute abdominal pain.
      Exploratory laparotomy revealed appendicitis, pathology of which showed numerous
      eggs consistent with Taenia species. Although Taenia appendicitis is rare, it
      should be considered in the differential diagnosis of patients presenting with
      appendicitis from endemic parts of the world.

PMID- 19589066
TI  - Developing kernel and rachis node induce the trichothecene pathway of Fusarium
      graminearum during wheat head infection.
AB  - The fungal pathogen Fusarium graminearum is the most common agent of Fusarium
      head blight (FHB) in small grain cereals and cob rot of maize. The threat posed
      by this fungus is due to a decrease in yield and, additionally, mycotoxin
      contamination of the harvested cereals. Among the mycotoxins, trichothecenes
      influence virulence of F. graminearum in a highly complex manner that is strongly
      host- as well as chemotype-specific. The factors inducing mycotoxin production
      during plant infection are still unknown. To evaluate the induction of the
      trichothecene pathway, the green fluorescence protein (GFP) gene was fused to the
      promoter of the TRI5 gene coding for the trichodiene synthase and integrated into
      the genome by homologous integration. The resulting mutant contains a fully
      functional TRI5 gene ensuring virulence on wheat and exhibits GFP driven by the
      endogenous TRI5 promoter. We are now able to monitor the induction of
      trichothecenes under real-time conditions. To localize the fungus in the plant
      tissue, the dsRed gene was integrated under constitutive control of the glycerol
      3-phosphate dehydrogenase (gpdA) promoter. We are now able to show that, first,
      induction of GFP as well as trichothecene production in the reporter strain
      reflects TRI5 induction and trichothecene production in the wild type; second,
      expression of TRI5 is inducible during growth in culture; and, third,
      trichothecene production is not uniformly induced during the onset of infection
      but is tissue specific during fungal infection of wheat.

PMID- 19589067
TI  - Type IV Pili are required for virulence, twitching motility, and biofilm
      formation of acidovorax avenae subsp. Citrulli.
AB  - Acidovorax avenae subsp. citrulli is the causal agent of bacterial fruit blotch
      (BFB), a threatening disease of watermelon, melon, and other cucurbits. Despite
      the economic importance of BFB, relatively little is known about basic aspects of
      the pathogen's biology and the molecular basis of its interaction with host
      plants. To identify A. avenae subsp. citrulli genes associated with
      pathogenicity, we generated a transposon (Tn5) mutant library on the background
      of strain M6, a group I strain of A. avenae subsp. citrulli, and screened it for
      reduced virulence by seed-transmission assays with melon. Here, we report the
      identification of a Tn5 mutant with reduced virulence that is impaired in pilM,
      which encodes a protein involved in assembly of type IV pili (TFP). Further
      characterization of this mutant revealed that A. avenae subsp. citrulli requires
      TFP for twitching motility and wild-type levels of biofilm formation. Significant
      reductions in virulence and biofilm formation as well as abolishment of twitching
      were also observed in insertional mutants affected in other TFP genes. We also
      provide the first evidence that group I strains of A. avenae subsp. citrulli can
      colonize and move through host xylem vessels.

PMID- 19589068
TI  - Full-size ABC transporters from the ABCG subfamily in medicago truncatula.
AB  - Full-size ATP-binding cassette (ABC) transporters belonging to the ABCG subfamily
      are unique for plants and fungi. There is growing evidence that certain of these
      proteins play a role in plant defense or signaling systems. As yet, a complete
      set of full-size ABCG protein genes has been inventoried and classified in only
      two plants: Arabidopsis thaliana and Oryza sativa. Recently, a domain-based
      clustering analysis has predicted the presence of at least 12 genes encoding such
      proteins in the Lotus japonicus genome. Here, we identify and classify 19 genes
      coding full-size ABCG proteins in Medicago truncatula, a model legume plant. We
      have found that the majority of these genes are expressed in roots and flowers
      whereas only a few are expressed in leaves. Expression of several has been
      induced upon pathogenic infection in both roots and leaves. ABCG messenger RNAs
      have been detected in root nodules forming during symbiosis of legume plants and
      nitrogen-fixing bacteria. The data presented provide a scaffold for further
      studies of the physiological function of Medicago ABCG transporters and their
      possible role in modulating plant-microorganism interactions.

PMID- 19589069
TI  - Repeat-induced point mutation (RIP) as an alternative mechanism of evolution
      toward virulence in Leptosphaeria maculans.
AB  - Three avirulence genes, AvrLm1, AvrLm6, and AvrLm4-7, were recently identified in
      Leptosphaeria maculans and found to be localized as solo genes within large
      noncoding, heterochromatin-like regions mainly composed of retrotransposons,
      truncated and degenerated by repeat-induced point mutation (RIP). The Rlm6
      resistance gene has been overcome within 3 years in outdoor experiments in France
      and, here, we investigate the molecular basis of evolution toward virulence at
      the AvrLm6 locus. A region of 235 kb was sequenced in a virulent isolate and
      showed the deletion of AvrLm6 and three divergent mosaics of retrotransposons.
      AvrLm6 was found to be absent from 66% of 70 virulent isolates, with multiple
      events of deletion. The sequencing of virulent alleles in 24 isolates revealed a
      few cases of point mutations that had created stop codons in the sequence. The
      most frequent mutation events, however, were RIP, leading to the modification of
      4 to 9% of the bases compared with the avirulent allele and generating 2 to 4
      stop codons. Thus, RIP is described for the first time as an efficient mechanism
      leading to virulence and the multiple patterns of mutation observed suggest that
      multiple RIP events could occur independently in a single field population during
      1 year.

PMID- 19589070
TI  - The YAP1 homolog-mediated oxidative stress tolerance is crucial for pathogenicity
      of the necrotrophic fungus Alternaria alternata in citrus.
AB  - Citrus brown spot disease is caused by the necrotrophic fungus Alternaria
      alternata. Its pathogenic capability has been thought to depend exclusively on
      the production of host-selective ACT toxin. However, circumvention of plant
      defenses is also likely to be important for the disease process. To investigate
      the fungal response to host-generated reactive oxygen species (ROS), we cloned
      and characterized the AaAP1 gene of A. alternata, which encodes a polypeptide
      resembling yeast YAP1-like transcriptional activators implicated in cellular
      responses to stress. Expression of the AaAP1 gene in a wild-type strain was
      primarily induced by H(2)O(2) or ROS-generating oxidants. Using a loss-of
      function mutation in the AaAP1 gene, we demonstrated an essential requirement for
      oxidative tolerance during the host invasion step. Mutants lacking AaAP1 showed
      increased sensitivity to H(2)O(2) and loss of fungal pathogenicity. The
      DeltaAaAP1 null mutant did not cause any visible necrotic lesions on wounded or
      unwounded leaves of citrus cv. Minneola. Compared with the wild type, the null
      mutant displayed lower catalase, peroxidase, and superoxide dismutase activities.
      All mutant phenotypes were restored to the wild type in fungal strains expressing
      a functional copy of AaAP1. Upon exposure to H(2)O(2), the AaAP1::sGFP (synthetic
      green fluorescent protein) fusion protein became localized in the nucleus.
      Inoculation of the mutant with NADPH oxidase inhibitors partially restored fungal
      pathogenicity. Our results highlight the global regulatory role of a YAP1 homolog
      in response to oxidative stress in A. alternata and provide insights into the
      critical role of ROS detoxification in the pathogenicity of A. alternata.

PMID- 19589071
TI  - The ERECTA Receptor-Like Kinase Regulates Cell Wall-Mediated Resistance to
      Pathogens in Arabidopsis thaliana.
AB  - Some receptor-like kinases (RLK) control plant development while others regulate
      immunity. The Arabidopsis ERECTA (ER) RLK regulates both biological processes. To
      discover specific components of ER-mediated immunity, a genetic screen was
      conducted to identify suppressors of erecta (ser) susceptibility to
      Plectosphaerella cucumerina fungus. The ser1 and ser2 mutations restored disease
      resistance to this pathogen to wild-type levels in the er-1 background but failed
      to suppress er-associated developmental phenotypes. The deposition of callose
      upon P. cucumerina inoculation, which was impaired in the er-1 plants, was also
      restored to near wild-type levels in the ser er-1 mutants. Analyses of er cell
      walls revealed that total neutral sugars were reduced and uronic acids increased
      relative to those of wild-type walls. Interestingly, in the ser er-1 walls,
      neutral sugars were elevated and uronic acids were reduced relative to both er-1
      and wild-type plants. The cell-wall changes found in er-1 and the ser er-1
      mutants are unlikely to contribute to their developmental alterations. However,
      they may influence disease resistance, as a positive correlation was found
      between uronic acids content and resistance to P. cucumerina. We propose a
      specific function for ER in regulating cell wall-mediated disease resistance that
      is distinct from its role in development.

PMID- 19589072
TI  - Pseudomonas syringae pv. phaseolicola Mutants Compromised for type III secretion
      system gene induction.
AB  - Pseudomonas syringae bacteria utilize the type III secretion system (T3SS) to
      deliver effector proteins into host cells. The T3SS and T3 effector genes
      (together called the T3 genes hereafter) are repressed in nutrient-rich medium
      but rapidly induced after the bacteria are transferred into minimal medium or
      infiltrated into plants. The induction of the T3 genes is mediated by HrpL, an
      alternative sigma factor that recognizes the conserved hrp box motif in the T3
      gene promoters. The induction of hrpL is mediated by HrpR and HrpS, two
      homologous proteins that bind the hrpL promoter. To identify additional genes
      involved in regulation of the T3 genes, we screened for the P. syringae pv.
      phaseolicola NPS3121 transposon-tagged mutants with reduced induction of avrPto
      luc and hrpL-luc, reporter genes for promoters of effector gene avrPto and hrpL,
      respectively. Determination of the transposon-insertion sites revealed genes with
      putative functions in signal transduction and transcriptional regulation, protein
      synthesis, and basic metabolism. A transcriptional regulator (AefR(NPS3121)) was
      identified in our screen that is homologous to AefR of P. syringae pv. syringae
      strain B728a, a regulator of the quorum-sensing signal and epiphytic traits, but
      was not known to regulate the T3 genes. AefR(NPS3121) in P. syringae pv.
      phaseolicola NPS3121 and AefR in P. syringae pv. syringae B728a behave similarly
      in regulating the quorum-sensing signal in liquid medium but differ in regulating
      the epiphytic traits, including swarming motility, leaf entry, and epiphytic
      survival.

PMID- 19589073
TI  - Are grapevine stomata involved in the elicitor-induced protection against downy
      mildew?
AB  - Stomata, natural pores bordered by guard cells, regulate transpiration and gas
      exchanges between plant leaves and the atmosphere. These natural openings also
      constitute a way of penetration for microorganisms. In plants, the perception of
      potentially pathogenic microorganisms or elicitors of defense reactions induces a
      cascade of events, including H(2)O(2) production, that allows the activation of
      defense genes, leading to defense reactions. Similar signaling events occur in
      guard cells in response to the perception of abscisic acid (ABA), leading to
      stomatal closure. Moreover, few elicitors were reported to induce stomatal
      closure in Arabidopsis and Vicia faba leaves. Because responses to ABA and
      elicitors share common signaling events, it led us to question whether stomatal
      movements and H(2)O(2) production in guard cells could play a key role in
      elicitor-induced protection against pathogens that use stomata for infection.
      This study was performed using the grapevine-Plasmopara viticola pathosystem.
      Using epidermal peels, we showed that, as for ABA, the elicitor-induced stomatal
      closure is mediated by reactive oxygen species (ROS) production in guard cells.
      In plants, we observed that the protection against downy mildew induced by some
      elicitors is probably not due only to effects on stomatal movements or to a guard
      cell-specific activation of ROS production.

PMID- 19589074
TI  - Does botrytis cinerea Ignore H(2)O(2)-induced oxidative stress during infection?
      Characterization of botrytis activator protein 1.
AB  - Botrytis cinerea is a phytopathogen infecting a broad range of plants including
      strawberries and grapevine. During infection, the necrotrophic fungus is exposed
      to reactive oxygen species (ROS) released by the oxidative burst, an early plant
      defense reaction. B. cinerea even produces ROS itself in planta. This raises
      questions about how the pathogen senses and responds to the host defense reaction
      and which role the pathogen's oxidative stress response systems play. Functional
      analysis of the AP-1 transcription factor Bap1 confirmed its role as a pivotal
      regulator of ROS detoxification in vitro. Macroarray analysis revealed 99
      H(2)O(2)-induced Bap1 target genes, of which several genes encoded ROS-degrading
      enzymes as well as other central components of the cellular redox status.
      However, Bap1 is not essential for pathogenesis. In planta analyses revealed that
      the Bap1 target genes were not expressed 2 days postinoculation although H(2)O(2)
      was detectable, proving that the normal virulence of the Deltabap1 mutant is not
      due to alternative regulation of the major oxidative stress response system in
      planta. The fungus obviously does not suffer H(2)O(2)-induced oxidative stress in
      planta, questioning classical ideas about the role of the oxidative burst in the
      infection process.

PMID- 19589075
TI  - Identification of Beet necrotic yellow vein virus P25 pathogenicity factor
      interacting sugar beet proteins that represent putative virus targets or
      components of plant resistance.
AB  - Beet necrotic yellow vein virus (BNYVV) induces the most important disease
      threatening sugar beet. The growth of partially resistant hybrids carrying
      monogenic dominant resistance genes stabilize yield but are unable to entirely
      prevent virus infection and replication. P25 is responsible for symptom
      development and previous studies have shown that recently occurring resistance
      breaking isolates possess increased P25 variability. To better understand the
      viral pathogenicity factor's interplay with plant proteins and to possibly
      unravel the molecular basis of sugar beet antivirus resistance, P25 was applied
      in a yeast two-hybrid screen of a resistant sugar beet cDNA library. This screen
      identified candidate proteins recognized as orthologues from other plant species
      which are known to be expressed following pathogen infection and involved in
      plant defense response. Most of the candidates potentially related to host
      pathogen interactions were involved in the ubiquitylation process and plants
      response to stress, and were part of cell and metabolism components. The
      interaction of several candidate genes with P25 was confirmed in Nicotiana
      benthamiana leaf cells by transient agrobacterium-mediated expression applying
      bimolecular fluorescence complementation assay. The putative functions of several
      of the candidates identified support previous findings and present first targets
      for understanding the BNYVV pathogenicity and antivirus resistance mechanism.

PMID- 19589076
TI  - Complete genome sequence of citrus huanglongbing bacterium, 'Candidatus
      Liberibacter asiaticus' obtained through metagenomics.
AB  - Citrus huanglongbing is the most destructive disease of citrus worldwide. It is
      spread by citrus psyllids and is associated with a low-titer, phloem-limited
      infection by any of three uncultured species of alpha-Proteobacteria, 'Candidatus
      Liberibacter asiaticus', 'Ca. L. americanus', and 'Ca. L. africanus'. A complete
      circular 'Ca. L. asiaticus' genome has been obtained by metagenomics, using the
      DNA extracted from a single 'Ca. L. asiaticus'-infected psyllid. The 1.23-Mb
      genome has an average 36.5% GC content. Annotation revealed a high percentage of
      genes involved in both cell motility (4.5%) and active transport in general
      (8.0%), which may contribute to its virulence. 'Ca. L. asiaticus' appears to have
      a limited ability for aerobic respiration and is likely auxotrophic for at least
      five amino acids. Consistent with its intracellular nature, 'Ca. L. asiaticus'
      lacks type III and type IV secretion systems as well as typical free-living or
      plant-colonizing extracellular degradative enzymes. 'Ca. L. asiaticus' appears to
      have all type I secretion system genes needed for both multidrug efflux and toxin
      effector secretion. Multi-protein phylogenetic analysis confirmed 'Ca. L.
      asiaticus' as an early-branching and highly divergent member of the family
      Rhizobiaceae. This is the first genome sequence of an uncultured alpha
      proteobacteria that is both an intracellular plant pathogen and insect symbiont.

PMID- 19589077
TI  - The ThPG1 endopolygalacturonase is required for the trichoderma harzianum-plant
      beneficial interaction.
AB  - Considering the complexity of the in vivo interactions established by a
      mycoparasitic biocontrol agent at the plant rhizosphere, proteomic, genomic, and
      transcriptomic approaches were used to study a novel Trichoderma gene coding for
      a plant cell wall (PCW)-degrading enzyme. A proteome analysis, using a three
      component (Trichoderma spp.-tomato plantlets-pathogen) system, allowed us to
      identify a differentially expressed Trichoderma harzianum endopolygalacturonase
      (endoPG). Spot 0303 remarkably increased only in the presence of the soilborne
      pathogens Rhizoctonia solani and Pythium ultimum, and corresponded to an
      expressed sequence tag from a T. harzianum T34 cDNA library that was constructed
      in the presence of PCW polymers and used to isolate the Thpg1 gene. Compared with
      the wild-type strain, Thpg1-silenced transformants showed lower PG activity, less
      growth on pectin medium, and reduced capability to colonize tomato roots. These
      results were combined with microarray comparative data from the transcriptome of
      Arabidopsis plants inoculated with the wild type or a Thpg1-silenced transformant
      (ePG5). The endoPG-encoding gene was found to be required for active root
      colonization and plant defense induction by T. harzianum T34. In vivo assays
      showed that Botrytis cinerea leaf necrotic lesions were slightly smaller in
      plants colonized by ePG5, although no statistically significant differences were
      observed.

PMID- 19589078
TI  - A metabolic signature of the beneficial interaction of the endophyte
      paenibacillus sp. isolate and in vitro-grown poplar plants revealed by
      metabolomics.
AB  - Metabolic profiling via gas chromatography coupled to mass spectrometry was used
      to investigate the influence of endophytic bacteria on shoots of in vitro-grown
      poplar plants free from culturable endophytic bacteria. The results demonstrate
      that the occurrence of an endophytic Paenibacillus strain strongly affects the
      composition of the plant metabolites of in vitro-grown poplars. Eleven
      metabolites were significantly changed between inoculated and non-inoculated
      poplar plants as determined by two independent experiments. Detected shifts in
      the primary metabolism of the poplar plants pointed to a mutualistic interaction
      between bacteria able to fix nitrogen and the host plant with altered nitrogen
      assimilation patterns. The corresponding metabolic signature comprises increased
      asparagine and urea levels as well as depleted sugars and organic acids of the
      tricarboxylic acid cycle. These observations coincide with the fact that the
      Paenibacillus sp. strain P22 is able to grow without nitrogen in the medium,
      indicating nitrogen fixation from the air also known from other Paenibacillus
      spp. In combination with the detected plant-growth-promoting effects of the
      endophyte Paenibacillus P22, a novel mutualistic interaction is observed.

PMID- 19589079
TI  - Association of noncirrhotic portal hypertension in HIV-infected persons and
      antiretroviral therapy with didanosine: a nested case-control study.
AB  - BACKGROUND: Noncirrhotic portal hypertension (NCPH) is a newly described life
      threatening liver disease of unknown cause in human immunodeficiency virus (HIV)
      infected persons. Postulated pathogenesis includes prolonged exposure to
      antiretroviral therapy, particularly didanosine. METHODS: We performed a nested
      case-control study including 15 patients with NCPH and 75 matched control
      subjects of the Swiss HIV Cohort Study to investigate risk factors for the
      development of NCPH. Matching criteria were similar duration of HIV infection,
      absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis
      in the respective case. RESULTS: All 15 case patients had endoscopically
      documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died
      because of hepatic complications. At NCPH diagnosis, case patients and control
      subjects were similar concerning sex; race; Centers for Disease Control and
      Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and
      lipodystrophy. Differences were found in age (conditional logistic regression
      odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1);
      homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count <200 cells/microL
      (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine
      aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline
      phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower
      than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral
      therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase
      inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1),
      ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9)
      were longer in case patients. Exposure to nonnucleoside reverse-transcriptase
      inhibitor and other protease inhibitors were not different between groups. In
      bivariable models, only the association of NCPH with didanosine exposure was
      robust; other covariables were not independent risk factors. CONCLUSIONS: We
      found a strong association between prolonged exposure to didanosine and the
      development of NCPH.

PMID- 19589080
TI  - Bordetella pertussis booster vaccination for health care personnel immediately
      following a pertussis outbreak in a hospital?

PMID- 19589081
TI  - Hepatitis C treatment for injection drug users: a review of the available
      evidence.
AB  - Globally, approximately 90% of new hepatitis C infections are attributed to
      injection drug use, but there is a continuing reluctance to treat injection drug
      users (IDUs). There is evidence that a sizeable proportion of IDUs who begin
      hepatitis C treatment achieve a sustained virological response (SVR). In chronic
      hepatitis C treatment trials, the SVR rate among IDUs appears to be comparable to
      rates among non-IDUs; in trials prescribing pegylated interferon plus ribavirin,
      the median rate of SVR among IDUs was 54.3% (range, 18.1%-94.1%), compared with
      54%-63% in the large treatment trials. Few trials of acute hepatitis C treatment
      report on outcomes in IDUs; however, among these trials, the SVR among IDUs was
      68.5% (n=89), compared with 81.5% among non-IDUs (n=65). Additional studies are
      required to determine the optimal circumstances for treatment (e.g., enrollment
      in drug treatment, the requirement of a period of abstinence from injection drug
      use, or the establishment of multidisciplinary treatment programs).

PMID- 19589082
TI  - contribution of genetically restricted, methicillin-susceptible strains to the
      ongoing epidemic of community-acquired Staphylococcus aureus infections.
AB  - BACKGROUND: Within the current worldwide epidemic of community-acquired
      Staphylococcus aureus infections, attention has focused on the role of
      methicillin-resistant strains. We characterize methicillin-susceptible strains
      that also contribute to this epidemic. METHODS: We tracked cultures from abscess
      specimens submitted to the microbiology laboratory at St. Louis Children's
      Hospital and examined Panton-Valentine leukocidin (PVL) genes in methicillin
      susceptible S. aureus (MSSA) isolates. We further characterized some isolates by
      multilocus sequence typing, pulsed-field gel electrophoresis, antibiotic
      susceptibility, accessory gene regulator (agr) allele, and presence of the arcA
      gene of the arginine catabolic mobile element. RESULTS: From 1999 to 2007, we
      detected a 250-fold increase in cultures of abscesses yielding methicillin
      resistant S. aureus (MRSA) and a 5-fold increase in abscess cultures yielding
      MSSA. MSSA isolates from abscesses and wounds were more likely to encode PVL than
      isolates from other sources. In contrast to PVL-negative isolates of MSSA, which
      were genetically diverse, PVL-positive isolates were predominantly multilocus
      sequence typing type 8 and agr type 1. More than half of PVL-positive MSSA
      isolates were resistant to erythromycin and susceptible to clindamycin with the
      absence of inducible resistance, a pattern uncommon in PVL-negative MSSA but
      frequent in the USA300 clone of MRSA. In addition, pulsed-field gel
      electrophoresis of PVL-positive MSSA strains revealed the USA300 pattern.
      CONCLUSIONS: In addition to methicillin-resistant strains, the current epidemic
      of S. aureus infections includes infections caused by methicillin-susceptible
      strains that are closely related genetically and share phenotypic characteristics
      other than susceptibility to methicillin. These findings suggest that factors
      other than methicillin resistance are driving the epidemic.

PMID- 19589083
TI  - Dexamethasone in Cryptococcus gattii central nervous system infection.
AB  - Clinical outcomes were reviewed for 4 patients with Cryptococcus gattii central
      nervous system infection who received dexamethasone for the treatment of
      persisting mental status abnormalities and focal lesions on brain scan despite
      culture-negative cerebrospinal fluid and the management of intracranial pressure.
      Favorable clinical responses were observed in 3 patients. Although
      corticosteroids are not recommended for the treatment of cryptococcal meningitis,
      these observations suggest that dexamethasone should be further evaluated in this
      subset of patients.

PMID- 19589084
TI  - Kinetics of pertussis immune responses to tetanus-diphtheria-acellular pertussis
      vaccine in health care personnel: implications for outbreak control.
AB  - We assessed the kinetics of the humoral immune response to pertussis antigens
      following vaccination of health care personnel with adult tetanus-diphtheria
      acellular pertussis vaccine (Tdap). By 2 weeks after vaccination, 88%-94% of
      subjects demonstrated a booster response. This brisk response of adults to Tdap
      supports a role for vaccination in pertussis outbreak control.

PMID- 19589090
TI  - Investigational vasopressin receptor modulators in the pipeline.
AB  - The vasopressin system is complex and interacts with the central nervous,
      cardiovascular, renal, and hematological systems. Vasopressin plays an important
      role in the control of blood osmolarity and vascular tone, but is also involved
      in many other physiological events, which are mediated mainly via three types of
      vasopressin receptor: V1R, V2R, and V3R. V1R primarily mediate the vascular, and
      V2R the aquaretic, effects of vasopressin. Vasopressin may also interact with
      other receptors, like adrenergic and angiotensin-II receptors, or with distinct
      biological pathways, including those of nitric oxide and the K(ATP) channel.
      There are numerous clinical situations where vasopressin receptor modulators
      (agonists or antagonists) could be used. Currently, vasopressin and terlipressin
      are most commonly used to stimulate V1R in vasodilatory shock and cardiac arrest,
      while desmopressin, a synthetic analogue of vasopressin, acts on V2R; but new
      molecules are becoming available in the treatment of inappropriate antidiuretic
      hormone (ADH) secretion.

PMID- 19589091
TI  - Novel inhibitors of the PI3K family.
AB  - PI3K is an important node regulating the signaling of several essential
      biological processes. PI3K catalyzes the phosphorylation in position 3 of the
      inositol ring of phosphatidyl-inositide producing important lipid second
      messengers. The products of PI3K activity recruit PDK1 and AKT Ser/Thr kinases to
      the plasma membrane where they get activated transducing a potent proliferative
      and anti-apoptotic signal to the cell. PI3K is activated by growth factors,
      insulin and GPCR activation. Furthermore, PI3K can be activated by direct binding
      to oncogenic Ras proteins. PI3K is commonly altered in human cancers by point
      activating mutations or by amplification. Furthermore, other proteins of the
      route are also altered in human tumors (such as phosphatase and tensin homolog in
      chromosome 10 or human EGF receptor 2) providing constitutive activation of PI3K.
      The evidence indicates that the PI3K pathway is a potential target for cancer
      chemotherapy. Indeed, many companies and academic laboratories have initiated a
      variety of approaches to inhibit the PI3K pathway at different points. In this
      work, we review the targeting of PI3K protein for therapeutical intervention.

PMID- 19589092
TI  - An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's
      disease.
AB  - Several epidemiological studies suggest that long-term use of non-steroidal anti
      inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD),
      especially for patients carrying one or more epsilon4 allele of the
      apolipoprotein E. The biological mechanism of this protection is not completely
      understood and may involve inhibition of COX activity, inhibition of beta
      amyloid(1-42) (Abeta42) production and aggregation, inhibition of beta-secretase
      activity, activation of PPAR-gamma or stimulation of neurotrophin synthesis.
      Unfortunately, long-term, placebo-controlled clinical trials with both non
      selective and COX-2 selective NSAIDs in AD patients produced negative results. A
      secondary prevention study with rofecoxib in patients with mild cognitive
      impairment and a primary prevention study with naproxen and celecoxib in elderly
      subjects with a family history of AD were also negative. All these failures have
      diminished the hope that NSAIDs could be beneficial in the treatment of AD. It is
      hypothesized that the chronic use of NSAIDs may be beneficial only in the normal
      brain by inhibiting the production of Abeta42. Once the Abeta deposition process
      has started, NSAIDs are no longer effective and may even be detrimental because
      of their inhibiting activity on activated microglia of the AD brain, which
      mediates Abeta clearance and activates compensatory hippocampal neurogenesis.

PMID- 19589093
TI  - Drugs in development for the treatment of schizophrenia.
AB  - The overall outcome in schizophrenia is generally poor, despite the undisputed
      efficacy of antipsychotics in treating the acute symptoms of psychosis. There
      remains a subset of patients who are refractory to treatment. Also, for most
      patients treatment is not effective against the full spectrum of symptoms
      including negative and cognitive symptoms, and severe functional deficits
      persist. Further, while the newer drugs produce fewer motor side effects, other
      safety and tolerability concerns have emerged. Since the advent of antipsychotic
      therapy in the early 1950s, subsequent advances have been modest. While the
      mechanism of action of the first-generation antipsychotics appears closely linked
      to D2 antagonism, the second-generation antipsychotics have broader receptor
      binding profiles, particularly 5-HT receptor antagonism. Attempts are now being
      made to develop antipsychotics with a wider spectrum of efficacy and a more
      favourable safety and tolerability profile by further exploring the therapeutic
      potential of D2 and 5-HT2 receptors, as well as investigating other putative
      mechanisms of action. This article adds to the current literature by providing an
      up-to-date review of antipsychotic drugs currently in development, focusing on
      the findings to date for compounds that are presently in Phase III clinical
      trials. While no exciting breakthroughs appear imminent, several drugs in early
      development have great potential.

PMID- 19589094
TI  - Investigation of the chemical-induced selective type II (T(H)2) allergic response
      in mice: effect of the length of the sensitizing phase.
AB  - Allergies are immune system disorders characterized by abnormal, acquired
      sensitivity to various environmental chemicals. We investigated the mechanism of
      chemical-induced selective type II (T(H)2) allergy by using three different
      sensitization protocols and the well-known respiratory sensitizer trimellitic
      anhydride (TMA). Mice were sensitized for either 1, 2, or 3 weeks. For each
      sensitization schedule, the mice were allocated into 3 or 4 groups: -/- group,
      both sensitized and challenged with vehicle; -/+ group, sensitized with vehicle
      and challenged with 0.1% TMA; +/- group, sensitized with 1% TMA and challenged
      with vehicle; and +/+ group, both sensitized and challenged with 0.1% TMA. After
      challenge, we assayed the auricular lymph nodes of all mice for number of
      lymphocytes, surface antigen expression of B-cells, and local cytokine
      production, and we measured TMA-specific serum IgE levels. Some parameters in
      mice sensitized for 1 or 2 wk showed, at most, mild changes. In contrast, all
      parameters in animals receiving 3-wk sensitization showed marked increases, as
      well as marked increases in the IgE/major histocompatibility complex (MHC) Class
      II-positive B-cell population and T(H)2 cell production of IL-10 and IL-13. These
      results indicate that 3 wk of sensitization according to our protocol led to
      overt respiratory allergic reactions. While these studies showed that using the
      approach here, positive reactions were elicited using a typical allergen; whether
      the same events occur after sensitization by other chemicals that are found in
      the environment remains uncertain. These findings here should be regarded
      moreover as preliminary in scope and that additional studies with irritants,
      dermal sensitizers and other respiratory sensitizers are needed to further
      evaluate the overall sensitivity and selectivity of this novel protocol.

PMID- 19589095
TI  - Acetaminophen and lipopolysaccharide act in synergy for the production of pro
      inflammatory cytokines in murine RAW264.7 macrophages.
AB  - There is extensive evidence that pro-inflammatory cytokines produced by
      macrophages are involved in toxicity induced by drugs such as acetaminophen
      (APAP). We investigated the effect of subtoxic concentrations of acetaminophen in
      conjunction with bacterial lipopolysaccharide (LPS) on the expression of the pro
      inflammatory cytokines TNFalpha and IL-1beta using the mouse macrophage cell line
      RAW264.7 as a model. APAP alone induced in a dose-dependent manner the production
      of TNFalpha and IL-1beta in this cell line. When LPS was added to APAP-treated
      cells, the increase in TNFalpha and IL-1beta production observed was higher than
      the sum of cytokine amounts produced with each agent alone, suggesting a
      synergistic mechanism. Moreover, we found that p38MAPK, JNK, and ERK were
      activated by APAP or LPS alone or in association. In our model, the NFkappaB
      signaling pathway was not involved in cytokine production induced by APAP. When
      inhibiting MAPKs using pharmacological inhibitors, we showed that p38MAPK
      inhibition abrogated the synergistic effect of APAP and LPS found for TNFalpha
      production but not for IL-1beta production. JNK and ERK have comparable roles in
      the production of the cytokines. Furafylline, a CYP1A inhibitor, and
      indomethacin, a PGHS inhibitor, exhibited a significant inhibitory effect on
      TNFalpha and IL-1beta production induced by the APAP and LPS combination. This
      work suggests that in macrophages, APAP and LPS can synergistically provoke the
      induction of pro-inflammatory cytokines, an effect involving the MAPK pathway and
      APAP bioactivation by CYP and PGHS.

PMID- 19589096
TI  - The role of parity status on cigarette smoke-induced modulation of anti-tumor
      immune mechanisms.
AB  - Epidemiologic studies indicate that women who smoke cigarettes are more likely to
      experience adverse reproductive and immunological health effects. Despite these
      facts, 20-30% of American women still smoke during their reproductive years. As
      little is known of the relationship between smoking and the immune response
      during pregnancy, an investigation was conducted using parous and non-parous
      (virgin) B6C3F1 mice to investigate what role (if any) parity status had on
      cigarette smoke (CS) induced effects on immune functions important in
      surveillance against developing tumors. Pregnant mice were exposed to CS for 5
      d/wk ( 4 hr/d) from gestational day 4 to parturition; virgin mice were exposed
      for an equivalent amount of time. Smoke- and parity-associated alterations in
      pulmonary histology and lung inflammation, along with tumor cell host resistance,
      and cytotoxic T-lymphocyte (CTL) activity were examined either 24- 48 hr or 5 wk
      post-exposure/parturition; in the parous mice, gestational parameters were also
      evaluated. Exposure to CS significantly increased tumor susceptibility in virgin
      mice first injected with EL4 lymphoma cells at the 5 wk post-exposure timepoint;
      tumor incidence began to increase in smoke-exposed virgin mice as early as 24- 48
      hr post-exposure. Pregnancy itself increased tumor incidence in mice injected
      with EL4 cells 24- 48 hr after birth, but this effect then dissipated over 5 wk
      to levels seen in virgin mice. When EL4 injections were first performed at either
      timepoint in CS-exposed parous mice, the tumor incidence was not significantly
      different from that in the air-exposed parity-matched controls. CTL activity in
      CS-exposed parous mice was significantly increased from both nulliparous groups
      as well as from the parous air control mice examined 5 wk post-exposure. Results
      suggest that exposure to CS throughout gestation could act in combination with
      pregnancy-associated changes to up-regulate immune responses, potentially
      compromising fetal tolerance.

PMID- 19589097
TI  - Immunomodulatory effects of Pteridium aquilinum on natural killer cell activity
      and select aspects of the cellular immune response of mice.
AB  - Pteridium aquilinum (bracken fern) is one of the most common plants.
      Epidemiological studies have revealed a higher risk of certain types of cancers
      (i.e., esophageal, gastric) in people who consume bracken fern directly (as
      crosiers or rhizomes) or indirectly through the consumption of milk from
      livestock that fed on the plant. In animals, evidence exists regarding the
      associations between chronic bracken fern intoxication, papilloma virus
      infection, and the development of carcinomas. While it is possible that some
      carcinogens in bracken fern could be responsible for these cancers in both humans
      and animals, it is equally plausible that the observed increases in cancers could
      be related to induction of an overall immunosuppression by the plant/its various
      constituents. Under the latter scenario, normal tumor surveillance responses
      against nascent (non-bracken-induced) cancers or responses against viral
      infections (specifically those linked to induction of cancers) might be adversely
      impacted by continuous dietary exposure to this plant. Therefore, the overall
      objective of this study was to evaluate the immunomodulatory effects of bracken
      fern following daily ingestion of its extract by a murine host over a period of
      14 (or up to 30) days. In C57BL/6 mice administered (by gavage) the extract,
      histological analyses revealed a significant reduction in splenic white pulp
      area. Among a variety of immune response parameters/functions assessed in these
      hosts and isolated cells, both delayed-type hypersensitivity (DTH) analysis and
      evaluation of IFNgamma production by NK cells during T(H)1 priming were also
      reduced. Lastly, the innate response in these hosts-assessed by analysis of NK
      cell cytotoxic functionality-was also diminished. The results here clearly showed
      the immunosuppressive effects of P. aquilinum and that many of the functions that
      were modulated could contribute to the increased risk of cancer formation in
      exposed hosts.

PMID- 19589098
TI  - Immunotoxicity profile of natalizumab.
AB  - Natalizumab is a monoclonal antibody to human alpha4 integrin indicated for
      treatment of multiple sclerosis and Crohn's disease that prevents extravasation
      of leukocytes into surrounding tissues and their involvement in inflammation.
      Because alpha4 integrins and their receptors are involved in hematopoiesis and
      immune cell trafficking, natalizumab may interfere with these processes. We
      evaluated the effects of natalizumab on immune function in monkeys using in vitro
      and in vivo studies. Consistent with the pharmacologic effects of natalizumab,
      dose-related increases in white blood cell counts and spleen weights were
      observed. Administration to monkeys did not result in statistically significant
      alterations in the percentages of circulating B-cells, T-cells, T-cell subsets
      (CD4, CD8), or stem cells (CD34). A modest and highly variable delay in the
      primary humoral response to T-cell-dependent antigens was observed. Ex vivo
      studies using cells from natalizumab-treated monkeys demonstrated that treatment
      did not alter immune regulatory or effector cell functions in blood lymphocytes
      or spleen cells. A similar lack of effect on these functions was observed in
      vitro following treatment of PBMC and monocytes from human donors. Overall,
      natalizumab was well tolerated in monkeys, demonstrated the expected
      pharmacologic effect on cell trafficking, and showed no adverse effect on immune
      cell function.

PMID- 19589099
TI  - Genetic determinants of sensitivity to beryllium in mice.
AB  - Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung
      disease is caused by exposure to beryllium. This occupational hazard occurs in
      primary production and machining of Be-metal, BeO, beryllium - containing alloys,
      and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1
      hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated
      with risk of developing CBD. Because inbred strains of mice have not provided
      good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N
      background were developed; each contains a single allele of HLA-DPB1 that confers
      a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR
      approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR
      approximately 46). The mouse ear swelling test (MEST) was employed to determine
      if these different alleles would support a hypersensitivity response to
      beryllium. Mice were first sensitized on the back and subsequently challenged on
      the ear. In separate experiments, mice were placed into one of three groups
      (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the
      strain with the highest risk transgene, the Be/Be group was the only group that
      displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the
      baseline measurement (p < 0.05). No significant changes were observed in the
      other transgenic strains for any treatment condition. In addition, inter-strain
      differences in response to beryllium in seven inbred strains were investigated
      through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6,
      DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and
      C57/BL6 strains were the highest responders. Our results suggest that the HLA
      DPB1*1701 transgene product is an important risk factor for induction of the
      beryllium-sensitive phenotype. This model should be a useful tool for
      investigating beryllium sensitization.

PMID- 19589100
TI  - The cytotoxic effects of the organophosphates chlorpyrifos and diazinon differ
      from their immunomodulating effects.
AB  - Some organophosphate insecticides have immunomodulating capacities, but it is
      unknown whether different compounds within this class affect the immune system to
      the same extent. In this in vitro study, human immortalized T-lymphocytes or
      bronchial epithelial cells were treated with diazinon or chlorpyrifos in the
      absence or presence of cellular stress factors, thereby mimicking a stimulated
      immune system. Cytotoxicity was determined and cytokine release or cytokine
      promoter studies were performed to study immunomodulatory effects of these
      chemicals, whereby the same concentrations of chlorpyrifos and diazinon were
      used. Results showed that chlor- pyrifos was cytotoxic at concentrations >/= 250
      muM, whereas diazinon was not toxic at concentrations up to 1 mM. The
      immunomodulatory effects of these two compounds were similar for most cytokine
      promoters tested and induction of cellular stress enhanced these effects. The
      results were compared to data obtained with blood mononuclear cells, which
      confirmed the results of stably transfected cell lines, but refer to a higher
      sensitivity of primary cells. In conclusion, these two pesticides act in a
      different manner on cell viability and on some immune parameters, but cell
      viability was not linked to immunomodulation. The results also imply that healthy
      and diseased individuals are differentially affected by these pollutants.

PMID- 19589101
TI  - Heterophile antibodies may falsely increase or decrease thyroglobulin measurement
      in patients with differentiated thyroid carcinoma.
AB  - BACKGROUND: To examine the prevalence of significant interference from
      heterophile antibodies (HAb) in the measurement of serum thyroglobulin (Tg), we
      evaluated a large cohort of samples from patients with differentiated thyroid
      carcinoma (DTC). METHODS: Serum Tg measurements were performed in 406 serum
      samples before and after incubation of each serum sample in heterophile-blocking
      tubes (HBT) at room temperature for 1 h. We calculated the difference between the
      original Tg value and the value obtained after HBT treatment. We considered any
      sample showing an absolute percent difference >3 SD from the mean percent
      difference as being affected by HAb interference. RESULTS: We identified five
      patients (1%) as showing interference from HAb. Of these, three (60%) showed a
      false positive or falsely increased Tg concentration without any recurrence
      following clinical work-up; two (40%) showed a false negative or falsely reduced
      Tg levels, and metastases were detected in both cases by imaging procedures.
      CONCLUSIONS: HAb may increase as well as reduce the measured Tg in a significant
      number of patients. A positive HAb interference should be suspected if Tg
      elevation does not fit the clinical pictures. A negative interference is a more
      challenging problem because increases in Tg generally occur as the first sign of
      recurrence of DTC. Therefore, treatment using HBT tubes of all sera referred for
      Tg measurement should be considered in order to prevent both unwarranted
      investigations or therapy, and delayed diagnosis of recurrence in patients
      affected by DTC.

PMID- 19589102
TI  - Relationship of serum antioxidant micronutrients and sociodemographic factors to
      cervical neoplasia: a case-control study.
AB  - BACKGROUND: Although there have been some epidemiological studies on the effects
      of diet and nutritional status on cervical carcinogenesis, evidence for a
      protective effect of antioxidant micronutrients against cervical neoplasia is
      insufficient. The relationship between serum antioxidant micronutrients and
      sociodemographic factors and the risk of cervical neoplasia was investigated in
      this multi-center, case-control study. METHODS: The study population included
      women with histopathological diagnosis of cervical intraepithelial neoplasia
      (CIN) 1 (n=147), CIN 2/3 (n=177), cervical cancer (n=160), and a control group
      (n=378). Epidemiological data were collected and the serum concentrations of beta
      carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma
      tocopherol were measured using reverse-phase, gradient high-pressure liquid
      chromatography. RESULTS: Cervical cancer was found to be associated with older
      age, increased body mass index, and lower socioeconomic status as measured by
      education level and income. The mean serum concentrations of beta-carotene,
      lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol
      of cervical cancer patients were significantly lower than those of control
      subjects. Odds ratio adjusted for age, smoking status, alcohol consumption, and
      human papillomavirus infection status revealed a significant gradient of
      decreasing risk of CIN 1, CIN 2/3, and cervical cancer with increasing serum
      concentrations of most antioxidant micronutrients. CONCLUSIONS: The results of
      this study show an inverse association between serum antioxidant micronutrient
      concentrations and the risk of cervical neoplasia. These results suggest that
      antioxidant micronutrients play a role in the prevention of cervical
      carcinogenesis.

PMID- 19589103
TI  - Analysis and interpretation of drug testing results from patients on chronic pain
      therapy: a clinical laboratory perspective.
AB  - BACKGROUND: Recent guidelines recommend monitoring for opioid and drug use in
      patients with chronic pain to detect use of undisclosed or illicit substances,
      and to determine compliance with prescribed medications. We examined the
      technical and clinical impact of drug testing for patients on chronic pain
      therapy in our clinical laboratory. METHODS: Testing volumes were obtained for 4
      years. Volumes from three recent months were also examined in detail to determine
      average turnaround time, assay performance (i.e., number of positive screening
      and confirmatory tests and testing discrepancies) and consistency of patient
      results with medication history. RESULTS: Our testing volume continues to grow
      significantly, especially in the primary care setting, with an average yearly
      increase of 34%. Approximately 70% of patients confirmed positive for an opioid.
      Other drugs were positive in <30% of patients. Twenty-nine percent of patients
      tested positive for a medication without a prescription. Overall, the compliance
      rate was 85% indicating that 15% of patients had negative test results despite
      being prescribed a chronic pain medication. CONCLUSIONS: Clinical laboratories
      should consider the impact of these guidelines and examine options to optimize
      testing such as limiting or modifying the test panel.

PMID- 19589104
TI  - Unstimulated high sensitive thyroglobulin measurement predicts outcome of
      differentiated thyroid carcinoma.
AB  - BACKGROUND: Thyroglobulin (Tg) measurement following thyrotropin (TSH)
      stimulation is used in the follow-up of patients with differentiated thyroid
      carcinoma (DTC). However, high-sensitive assays allow accurate measurement of
      serum Tg even without TSH stimulation. Here, we prospectively evaluated the
      impact of unstimulated high-sensitive Tg measurement in early and long-term
      outcome of patients with DTC. METHODS: One hundred and ninety five patients
      affected with DTC were evaluated. Six months after thyroid ablation (i.e.,
      thyroidectomy plus radioiodine) serum Tg was measured during TSH-suppressive
      thyroxine (T4) treatment (onT4-Tg). Patients with undetectable onT4-Tg and
      negative neck ultrasound (US) were considered disease free and onT4-Tg was
      measured every 12 months for a mean follow-up of 6.8 (4.7-8.9) years. Patients
      with an increase in onT4-Tg underwent specific diagnostic work-up and appropriate
      treatment if necessary. RESULTS: Four patients showed recurrence at first follow
      up visit with a corresponding increase in onT4-Tg concentrations (sensitivity
      100%). Three patients had false positive onT4-Tg measurement (specificity 98%)
      with a spontaneous decrease within 3-6 months in all cases (specificity 100%).
      Three of 188 patients with undetectable serum onT4-Tg at first follow-up showed
      recurrence later with an increase in onT4-Tg as the first (n=2) or unique (n=1)
      sign of relapse (sensitivity 100%). Among 185 disease-free patients in a
      prolonged follow-up, 12 had a transient increase in onT4-Tg (specificity 91.6%).
      However, a spontaneous reduction within 3-6 months occurred in all cases
      (specificity 100%). CONCLUSIONS: Undetectable serum onT4-Tg using a high
      sensitivity immunoradiometric assay 6 months after thyroid ablation predicts low
      risk of DTC recurrence. When onT4-Tg became detectable during follow-up, the
      evaluation of Tg slope in a 3-6 months period accurately discriminated patients
      with DTC recurrence from those without recurrence. This helped avoid unnecessary
      diagnostic or therapeutic procedures.

PMID- 19589105
TI  - Haemolysis index--an estimate of preanalytical quality in primary health care.
AB  - BACKGROUND: Haemolysis is usually caused by inadequate specimen collection or
      preanalytical handling, and is suggested to be a suitable indicator of pre
      analytical quality. We investigated the prevalence of detectable haemolysis in
      all routine venous blood samples to identify differences in preanalytical
      quality. METHODS: Haemolysis index (HI) values were obtained from a Vitros 5,1 in
      the routine clinical chemistry laboratory for samples collected in primary health
      care centres (PHCs), nursing homes, and a hospital emergency department (ED).
      Haemolysis was defined as a HI > or =15 (detection limit). RESULTS: Samples from
      the PHC with the highest prevalence of haemolysis were 6.1 times (95% confidence
      interval (CI) 4.0-9.2) more often haemolysed compared to the centre with the
      lowest prevalence. Of the samples collected in primary health care, 10.4% were
      haemolysed compared to 31.1% in the ED (p<0.001). A notable difference in
      haemolysed samples was found between the ED section staffed by emergency medicine
      physicians and the section staffed by primary health care physicians (34.8% vs.
      11.3%, p<0.001). CONCLUSIONS: The significant variation in haemolysis indices
      among the investigated units is likely to reflect varying preanalytical
      conditions. The HI is a valuable tool for estimation and follow-up of
      preanalytical quality in primary health care.

PMID- 19589106
TI  - Quality of interpretative commenting on common clinical chemistry results in the
      Asia-Pacific region and Africa.
AB  - BACKGROUND: Interpretative commenting is an important activity of the clinical
      diagnostic laboratory. We describe a study of interpretative commenting abilities
      among senior laboratory professionals in the Asia-Pacific region and Africa.
      METHODS: Five sets of laboratory results reflecting common and important problems
      encountered in clinical chemistry were distributed at 4-weekly intervals to 31
      registered participants from countries in the Asia-Pacific region and Africa.
      Participants were asked to attach an interpretative comment to the results
      assuming that the requesting doctor had asked for an interpretation of the
      result. RESULTS: Twelve pathologists and 19 scientists from seven countries
      registered to participate and the overall reply rate was approximately 50% for
      the five cases. The quality of the comments returned by participants was diverse
      and some reflected incorrect or misleading interpretation and advice.
      CONCLUSIONS: While interpretative commenting is an important laboratory activity,
      the results of this study suggest that there is room for improvement in the
      quality of interpretative comments offered by senior laboratory professionals,
      even for commonly reported results relating to most prevalent and important
      public health conditions. Interpretative commenting should be formally taught
      during training of pathologists and scientists, and continuing professional
      development in this area is required for the provision of a quality
      interpretative service.

PMID- 19589107
TI  - Emotion and sudden cardiac death.

PMID- 19589108
TI  - Stroke prevention in atrial fibrillation: WATCHMAN versus warfarin.

PMID- 19589110
TI  - Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart
      failure: results of the GISSI-HF trial.
AB  - Epidemiological, experimental studies and post hoc analyses of randomized trials
      suggested that n-3 polyunsaturated fatty acids (PUFA) and statins could be
      beneficial in chronic heart failure. Two double-blind, placebo-controlled,
      randomized clinical trials investigated the efficacy and safety of n-3 PUFA 1 g
      daily (R1) and rosuvastatin 10 mg daily (R2) in patients with heart failure. In
      total, 6975 and 4574 patients were randomized in R1 and R2, respectively; the
      main reason for excluding patients from R2 being the open-label administration of
      statin treatment. Primary end points were death, and death or admission to
      hospital for cardiovascular reasons. n-3 PUFA, but not rosuvastatin,
      significantly decreased the two coprimary end points: 56 and 44 patients needed
      to be treated with n-3 PUFA for a median duration of 3.9 years to avoid one death
      or one cumulative event. Both drugs were safe and were tolerated. A simple and
      safe treatment with n-3 PUFA provides a beneficial advantage in patients with
      heart failure in a context of usual care.

PMID- 19589111
TI  - Combination of clopidogrel and aspirin for reduction of vascular events in
      patients with atrial fibrillation.

PMID- 19589112
TI  - Risk stratification in surgically repaired tetralogy of Fallot.
AB  - Tetralogy of Fallot is the most common form of congenital heart disease in
      implantable cardioverter-defibrillator (ICD) recipients. Indeed, sudden death of
      presumed arrhythmic etiology is the most frequent mode of demise in patients with
      surgically repaired tetralogy of Fallot, often in early-to-mid adulthood.
      Nevertheless, the overall annual incidence of sudden death is actually low.
      Therein lies the major challenge of risk stratification. This review highlights
      some of the complexities involved in risk stratifying patients with tetralogy of
      Fallot, underscoring the importance of avoiding oversimplification by means of a
      rigid algorithm that dictates therapy. To complement sound clinical judgment, a
      quantitative probabilistic approach is presented, which considers the body of
      literature from primary prevention ICD trials, risk factors identified by
      observational studies, the value of programmed ventricular stimulation and
      insights gleaned from studying ICD recipients with tetralogy of Fallot.

PMID- 19589113
TI  - Upstream therapy of atrial fibrillation.
AB  - Failure of current pharmacological therapy for atrial fibrillation in maintaining
      sinus rhythm may be due to structural atrial remodeling caused by inflammation
      and fibrosis. Upstream therapy that interferes in the structural remodeling
      process may be effective in maintaining sinus rhythm. This article reviews
      upstream therapy in atrial fibrillation. Various prospective and retrospective
      studies demonstrate that upstream therapy, consisting of angiotensin-converting
      enzyme inhibitors, angiotensin receptor blockers, statins, fish oils,
      glucocorticoids, or moderate physical activity, is associated with a reduced
      incidence of new-onset atrial fibrillation (i.e., primary prevention) and with a
      reduced recurrence of atrial fibrillation (i.e., secondary prevention). Larger
      clinical trials are required to further elucidate the position of upstream
      therapy in the primary and secondary prevention of atrial fibrillation.

PMID- 19589115
TI  - Right ventricular apical pacing: the unwanted model of cardiac stimulation?
AB  - Despite having a huge benefit in enabling heart rate control, cardiac pacing by
      stimulating the right ventricular apex causes an artificial iatrogenic left
      bundle-branch block-like syndrome. As a result, QRS widening and cardiac wall
      desynchronization occurs. The problems caused by this undesirable pacemaker side
      effect have been ignored, as they are counteracted by the great benefit of
      cardiac rate correction. However, the compelling evidence about its harmful
      effect presented in this article cannot be disregarded and should start an
      attitude change toward alternate sites of ventricular pacing and preclusion of
      the right ventricular apex stimulation.

PMID- 19589114
TI  - Catheter ablation for atrial fibrillation: a promising therapy for congestive
      heart failure.
AB  - Atrial fibrillation (AF) and congestive heart failure (CHF) are cardiovascular
      epidemics. Catheter ablation of AF is increasingly performed in patients with
      CHF. Atrioventricular junction ablation (AVJA) and pulmonary vein isolation are
      the two predominant ablation strategies used to treat AF patients who are
      refractory to drugs. In patients with CHF refractory to drugs, AVJA with a
      biventricular device is associated with improvement in exercise capacity and
      quality of life. However, in a head-to-head comparison, pulmonary vein antrum
      ablation was shown to be superior to AVJA. Cure of AF in patients with CHF
      resulted in more significant morphological and functional improvements than AVJA.

PMID- 19589116
TI  - Ventricular tachycardia and ventricular fibrillation.
AB  - Ventricular tachycardia and ventricular fibrillation are the most important
      causes of sudden cardiac death (SCD), particularly in those with structural heart
      disease and reduced left ventricular function. It is important to distinguish
      ventricular tachycardia from supraventricular tachycardia. A wide spectrum of
      ventricular arrhythmias exists, from those where the heart is structurally normal
      to those with structural heart disease. Each entity has a distinctive
      pathophysiology, treatment plan and prognostic outcome. Treatment modalities
      include simple beta-blockade to implantation of implantable cardiac defibrillator
      and ablative approaches. In general, those ventricular arrhythmias associated
      with a structurally normal heart are more benign than those associated with
      structural heart disease.

PMID- 19589117
TI  - Percutaneous heart valve replacement and repair: advances and future potential.
AB  - Major advancements in transcatheter valve therapies have occurred over the past
      decade that are worthy of focused attention. Some are on the verge of mainstay
      therapy, while others shine prosperously into the near future. This review
      summarizes the current status of transcatheter valve interventions and highlights
      some of the field's major advancements, technical challenges and future
      perspectives. It is, undoubtedly, a rapidly evolving discipline that portends
      immense promise in the evolution of cardiovascular medicine.

PMID- 19589118
TI  - Percutaneous pulmonary valve implantation: an update.
AB  - The field of percutaneous valvular interventions is one of the most exciting and
      rapidly developing within interventional cardiology. Percutaneous pulmonary valve
      implantation (PPVI) represents the first in-human application of these techniques
      and is a nonsurgical option for treating right ventricular outflow
      tract/pulmonary trunk dysfunction. With the growing numbers of patients with
      right ventricle to pulmonary artery conduit dysfunction after repair of
      congenital heart disease, the importance of a technique with lower morbidity and
      mortality, good patient acceptance and efficacy, that is comparable to surgery,
      cannot be underestimated. Over the last 9 years, PPVI has become a feasible, safe
      and effective treatment for both conduit stenosis and regurgitation. Median
      follow-up data show good freedom from reoperation and recatheterization and
      demonstrate that PPVI can postpone open-heart surgery, thereby potentially
      reducing the number of operations that patients have to undergo within their
      lifetime. Complications seen after PPVI, in particular stent fractures, can
      require reintervention in some cases (second stent-in-stent PPVI); however, valve
      competency remains good, with significant regurgitation during follow-up only
      seen in the context of occasional endocarditis. Attempts are now being made to
      prolong the lifespan of the device by reducing the incidence of stent fractures.
      Further, meticulous patient selection must be maintained to ensure that
      hemodynamic results are optimized and the safety of the procedure remains high.
      Finally, new devices have to be developed that will allow for PPVI in dilated,
      distensible outflow tracts, to offer this nonsurgical treatment option to a
      larger patient population with congenital heart disease.

PMID- 19589119
TI  - Clinical implications of cytokines in the critical-care unit.
AB  - To understand the role of different cytokines in the pathophysiology and
      management of different acute cardiovascular disorders in critically ill
      patients, we reviewed most of the pertinent articles published on Medline, Scopus
      and EBSCO host research databases from 1985 to January 2009. We used the indexing
      terms 'cytokines', 'cardiovascular', 'sepsis', 'critical care', 'myocardial
      dysfunction', 'shock', 'thromboembolism', 'inflammatory' and 'arrhythmias'.
      Myocardial dysfunction, dysrhythmic and thromboembolic disorders all appear
      associated with important fluctuations in cytokines. When and how to sample
      cytokine levels and the ways in which cytokines contribute to patient
      deterioration or improvement require further clinical studies. The measurement
      and interplay of several different cytokines may ultimately be of substantial
      clinical importance in the diagnosis, treatment and prognosis of patients with
      different acute cardiovascular disorders managed by critical-care physicians in
      intensive-care units. Although the role of cytokines in cardiovascular disorders
      is debatable, the clinical implication of cytokines in the critical-care unit is
      a new horizon that warrants more attention.

PMID- 19589120
TI  - Takotsubo or stress cardiomyopathy: role of nuclear cardiology using (123)I-MIBG.
AB  - Takotsubo cardiomyopathy, also known as broken heart syndrome or stress
      cardiomyopathy, is a very interesting syndrome of acute transient left
      ventricular dysfunction, usually following significant emotional stress. It was
      first described in Japan nearly two decades ago and many aspects of its
      pathogenesis still remain poorly understood. The incidence of out-of-hospital
      sudden death related to Takotsubo is currently unknown. Excess catecholamines
      following stress seem to trigger Takotsubo and play an important role. The
      clinical presentation resembles acute myocardial infarction, including chest
      tightness and/or dyspnea, ECG changes and elevated cardiac enzymes. However, in
      contrast to a typical acute myocardial infarction, no significant coronary
      lesions or thrombi are found on coronary angiography. Differentiating Takotsubo
      from acute myocardial infarction is important to avoid the unnecessary risks of
      thrombolytic therapy. Typically, left ventriculography shows marked abnormalities
      with akinesia in the mid-distal anterior wall and apex (occasionally involving
      other heart regions), giving a balloon shape to the left ventricle. The name
      Takotsubo originates from the shape of the left ventricle, which resembles a
      Japanese octopus-trapping pot. Hospital mortality is low but death can be caused
      by severe acute heart failure and/or ventricular arrhythmias. Typically, a
      stressful life event is reported preceding the acute symptoms. Takotsubo is most
      common in menopausal women although young individuals, including men, can also be
      affected. The autonomic nervous system has a defined role in the process. In this
      article, we will review the role of imaging the heart using (123)I-meta
      iodobenzylguanidine, a radioactive marker allowing mapping of the autonomic
      nervous system of the heart, in cases of suspected Takotsubo.

PMID- 19589121
TI  - Controversies in childhood arterial ischemic stroke and cerebral venous sinus
      thrombosis.
AB  - Arterial ischemic stroke (AIS) and cerebral venous sinus thrombosis (CVST) are
      increasingly recognized as causes of significant childhood disability. Lack of
      knowledge of the underlying pathogenic mechanisms results in diagnostic
      challenges and complicates therapeutic decisions, as reflected in divergent
      recommendations in three sets of pediatric stroke guidelines. In addition, there
      is a lack of robust evidence from clinical trials to underpin current
      recommendations regarding evaluation and treatment, in particular relating to
      antiplatelet therapy, anticoagulation and thrombolysis. With the advent of modern
      cerebrovascular imaging techniques, the optimal modality for investigating AIS
      and CVST is subject to debate. The potential role of inflammation in the genesis
      of arterial disease and the contribution of patent foramen ovale to the etiology
      of childhood AIS are contentious. Finally, the indications (and optimal
      technique) for surgical revascularization in children are not established. In
      this article, we review some of the current concepts and controversies in the
      investigation and management of AIS and CVST in children.

PMID- 19589123
TI  - Enhanced gene expression and reduced toxicity in mice using polyplexes of low
      molecular-weight poly(ethylene imine) for pulmonary gene delivery.
AB  - The aim of this study was to elicit improved gene expression and decreased
      cytotoxicity for pulmonary gene therapy by replacing the commonly used carrier 25
      kDa branched poly(ethylene imine) (BPEI) by two PEI derivatives, low-molecular
      weight PEI (LMWPEI) and polyethylene glycol-grafted PEI (PEGPEI). All polymers
      were shown to condense DNA to spherical particles of approximately 100 nm.
      Biocompatibility was investigated in vitro and in vivo. Although transfection was
      less efficient with LMWPEI-DNA in vitro, this polyplex caused the highest
      luciferase expression in the mouse lung after intratracheal instillation. While
      PEGPEI luciferase expression in vitro was approximately three times higher when
      compared to BPEI, a transfection rate at the level of naked DNA was observed in
      vivo. LMWPEI polyplexes were located in both the bronchial and alveolar cells,
      whereas BPEI polyplexes were mainly detected in bronchial cells. LMWPEI combines
      low cytotoxicity with high transfection efficiency in the mouse lung in vivo,
      rendering it a promising strategy for pulmonary gene delivery.

PMID- 19589122
TI  - Manidipine in hypertensive patients with metabolic syndrome: the MARIMBA study.
AB  - OBJECTIVES: To evaluate the effects of manidipine versus amlodipine on blood
      pressure, albuminuria, insulin sensitivity, adiponectin, TNF-alpha and C-reactive
      protein in nondiabetic subjects with metabolic syndrome (ATP-III definition),
      including impaired fasting glucose (>5.6 mmol/l) and hypertension. METHODS: In
      total, 64 patients were recruited and randomly assigned to manidipine 20 mg
      versus amlodipine 10 mg (for 12 +/- 2 weeks). RESULTS: Blood pressure was reduced
      to a similar extent (p < 0.001) by both treatments. Albuminuria was significantly
      reduced by manidipine (-37.3%; p = 0.003), but not by amlodipine. C-reactive
      protein was reduced similarly (p < 0.01) by both treatments. Plasma adiponectin
      was increased (32.9%; p = 0.011) and plasma TNF-alpha was reduced by manidipine (
      37.1%; p = 0.019), but neither was significantly changed by amlodipine. The HOMA
      insulin resistance index was significantly reduced by manidipine (-21.3%; p =
      0.007), but not by amlodipine (-8.3%; p = 0.062). Tolerability with manidipine
      was superior to that with amlodipine (p = 0.04). CONCLUSION: These data support
      the added value of manidipine in renal and metabolic protection beyond blood
      pressure reduction in the treatment of hypertensive patients with metabolic
      syndrome.

PMID- 19589124
TI  - Preparation, characterization and dissolution studies of fast release diclofenac
      sodium tablets from PVP solid dispersions.
AB  - Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used in the
      treatment of ankylosing spondylitis, rheumatoid arthritis and osteoarthritis. In
      this context, a rapid onset of action is required. Thus, the aim of this study
      was to formulate diclofenac sodium-PVP K-30 fast release tablets from solid
      dispersions. The physical state and drug:carrier interactions were analyzed by X
      ray diffraction and scanning electron microscopy and stability upon storage was
      also studied. Dissolution rate of diclofenac sodium from solid dispersions was
      markedly enhanced by increasing the polymer concentration.

PMID- 19589125
TI  - Quenching-induced deactivation of photosensitizer by nanoencapsulation to improve
      phototherapy of cancer.
AB  - Photodynamic therapy has emerged as a promising alternative to current cancer
      treatment. However, conventional photosensitizers have several limitations due to
      their unsuitable pharmaceutical formulations and lack of selectivity. Our
      strategy was to exploit the advantages of nanoparticles and the quenching-induced
      deactivation of the model photosensitizer hypericin to produce "activatable" drug
      delivery systems. Efficient fluorescence and activity quenching were achieved by
      increasing the drug-loading rate of nanoparticles. In vitro assays confirmed the
      reversibility of hypericin deactivation, as the hypericin fluorescence and
      photodynamic activity were recovered upon cell internalization.

PMID- 19589126
TI  - Noninvasive evaluation of tissue-engineered cartilage with time-resolved laser
      induced fluorescence spectroscopy.
AB  - Regenerative medicine requires noninvasive evaluation. Our objective is to
      investigate the application of time-resolved laser-induced fluorescence
      spectroscopy (TR-LIFS) using a nano-second-pulsed laser for evaluation of tissue
      engineered cartilage (TEC). To prepare scaffold-free TEC, articular chondrocytes
      from 4-week-old Japanese white rabbits were harvested, and were inoculated at a
      high density in a mold. Cells were cultured for 5 weeks by rotating culture (RC)
      or static culture (SC). The RC group and SC group at each week (n = 5), as well
      as normal articular cartilage and purified collagen type II (as controls), were
      analyzed by TR-LIFS. The peak wavelength was compared with those of type II
      collagen immunostaining and type II collagen quantification by enzyme-linked
      immunosorbent assay and tensile testing. The fluorescence peak wavelength of the
      TEC analyzed by this method shifted significantly in the RC group at 3 weeks, and
      in the SC group at 5 weeks (p < 0.01). These results correlated with changes in
      type II collagen (enzyme-linked immunosorbent assay) and changes in Young's
      modulus on tensile testing. The results were also supported by immunohistologic
      findings (type II collagen staining). Our findings show that TR-LIFS is useful
      for evaluating TEC.

PMID- 19589127
TI  - Asporin competes with decorin for collagen binding, binds calcium and promotes
      osteoblast collagen mineralization.
AB  - The interactions of the ECM (extracellular matrix) protein asporin with ECM
      components have previously not been investigated. Here, we show that asporin
      binds collagen type I. This binding is inhibited by recombinant asporin fragment
      LRR (leucine-rich repeat) 10-12 and by full-length decorin, but not by biglycan.
      We demonstrate that the polyaspartate domain binds calcium and regulates
      hydroxyapatite formation in vitro. In the presence of asporin, the number of
      collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2, were
      increased. Moreover, decorin or the collagen-binding asporin fragment LRR 10-12
      inhibited the pro-osteoblastic activity of full-length asporin. Our results
      suggest that asporin and decorin compete for binding to collagen and that the
      polyaspartate in asporin directly regulates collagen mineralization. Therefore
      asporin has a role in osteoblast-driven collagen biomineralization activity. We
      also show that asporin can be expressed in Escherichia coli (Rosetta-gami) with
      correctly positioned cysteine bridges, and a similar system can possibly be used
      for the expression of other SLRPs (small LRR proteoglycans/proteins).

PMID- 19589129
TI  - Structural aspects of RNA helicases in eukaryotic mRNA decay.
AB  - mRNA decay is critical for the regulation of gene expression and the quality
      control of mRNA. RNA helicases play a key role in eukaryotic mRNA decay. In
      general, RNA helicases utilize the energy of ATP hydrolysis to remodel RNA or RNA
      protein complexes, resulting in the separation of RNA duplex strand and/or
      displacement of proteins from the RNA molecule in RNP (ribonucleoprotein)
      complexes. Recently, high-resolution crystal structures of RNA helicases in mRNA
      decay have contributed a great deal to our understanding of these key molecules.
      In the present review, we focus on the structural and mechanistic aspects of
      three RNA helicases, Dhh1, Upf1 and eIF4AIII, that are involved in eukaryotic
      mRNA decay.

PMID- 19589131
TI  - Adequacy and tolerance to ass's milk in an Italian cohort of children with cow's
      milk allergy.
AB  - BACKGROUND: The therapy for cow's milk proteins allergy (CMPA) consists in
      eliminating cow's milk proteins (CMP) from the child's diet. Ass's milk (AM) has
      been recently considered as substitute of CMP. This prospective study
      investigated tolerance and nutritional adequacy of AM in children with CMPA from
      Southern Italy. METHODS: Thirty children (aged 6 months to 11 years) with
      suspected CMPA were enrolled. They underwent skin prick tests and bouble-blind,
      placebo controlled food challenge to CMP. After confirming the diagnosis of CMPA,
      patients received fresh AM in a open challenge. Specific serum CMP and AM IgE,
      and biochemical parameters in blood were also assessed. Auxological evaluations
      were performed in all subjects at entry (T0) and after 4-6 months (T1) of AM
      intake. RESULTS: Twenty-five children resulted elegible for the study, and 24 out
      of 25 subjects (96%) tolerated AM at the food challenge. Auxological data
      resulted improved by the end of the study in all patients, while blood
      biochemical parameters did not vary during the follow-up. CONCLUSION: Our data
      confirm the high rate of AM tolerability in children with moderate symptoms of
      CMPA. Moreover, we found that AM seems to have nutritional adequacy in subjects
      with a varied diet.

PMID- 19589130
TI  - Domain swapping reveals that the N-terminal domain of the sensor kinase KdpD in
      Escherichia coli is important for signaling.
AB  - BACKGROUND: The KdpD/KdpE two-component system of Escherichia coli regulates
      expression of the kdpFABC operon encoding the high affinity K+ transport system
      KdpFABC. The input domain of KdpD comprises a domain that belongs to the family
      of universal stress proteins (Usp). It has been previously demonstrated that UspC
      binds to this domain, resulting in KdpD/KdpE scaffolding under salt stress.
      However the mechanistic significance of this domain for signaling remains
      unclear. Here, we employed a "domain swapping" approach to replace the KdpD-Usp
      domain with four homologous domains or with the six soluble Usp proteins of E.
      coli. RESULTS: Full response to salt stress was only achieved with a chimera that
      contains UspC, probably due to unaffected scaffolding of the KdpD/KdpE signaling
      cascade by soluble UspC. Unexpectedly, chimeras containing either UspF or UspG
      not only prevented kdpFABC expression under salt stress but also under K+
      limiting conditions, although these hybrid proteins exhibited kinase and
      phosphotransferase activities in vitro. These are the first KdpD derivatives that
      do not respond to K+ limitation due to alterations in the N-terminal domain.
      Analysis of the KdpD-Usp tertiary structure revealed that this domain has a net
      positively charged surface, while UspF and UspG are characterized by net negative
      surface charges. CONCLUSION: The Usp domain within KdpD not only functions as a
      binding surface for the scaffold UspC, but it is also important for KdpD
      signaling. We propose that KdpD sensing/signaling involves alterations of
      electrostatic interactions between the large N- and C-terminal cytoplasmic
      domains.

PMID- 19589128
TI  - Polyamine catabolism and disease.
AB  - In addition to polyamine homoeostasis, it has become increasingly clear that
      polyamine catabolism can play a dominant role in drug response, apoptosis and the
      response to stressful stimuli, and contribute to the aetiology of several
      pathological states, including cancer. The highly inducible enzymes SSAT
      (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the
      generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to
      play critical roles in many normal and disease processes. The dysregulation of
      polyamine catabolism frequently accompanies several disease states and suggests
      that such dysregulation may both provide useful insight into disease mechanism
      and provide unique druggable targets that can be exploited for therapeutic
      benefit. Each of these enzymes has the potential to alter polyamine homoeostasis
      in response to multiple cell signals and the two oxidases produce the reactive
      oxygen species H2O2 and aldehydes, each with the potential to produce
      pathological states. The activity of SSAT provides substrates for APAO or
      substrates for the polyamine exporter, thus reducing the intracellular polyamine
      concentration, the net effect of which depends on the magnitude and rate of any
      increase in SSAT. SSAT may also influence cellular metabolism via interaction
      with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal
      of the present review is to cover those aspects of polyamine catabolism that have
      an impact on disease aetiology or treatment and to provide a solid background in
      this ever more exciting aspect of polyamine biology.

PMID- 19589132
TI  - Infarction in the territory of the anterior cerebral artery: clinical study of 51
      patients.
AB  - BACKGROUND: Little is known about clinical features and prognosis of patients
      with ischaemic stroke caused by infarction in the territory of the anterior
      cerebral artery (ACA). This single centre, retrospective study was conducted with
      the following objectives: a) to describe the clinical characteristics and short
      term outcome of stroke patients with ACA infarction as compared with that of
      patients with ischaemic stroke due to middle cerebral artery (MCA) and posterior
      cerebral artery (PCA) infarctions, and b) to identify predictors of ACA stroke.
      METHODS: Fifty-one patients with ACA stroke were included in the "Sagrat Cor
      Hospital of Barcelona Stroke Registry" during a period of 19 years (1986-2004).
      Data from stroke patients are entered in the stroke registry following a
      standardized protocol with 161 items regarding demographics, risk factors,
      clinical features, laboratory and neuroimaging data, complications and outcome.
      The characteristics of these 51 patients with ACA stroke were compared with those
      of the 1355 patients with MCA infarctions and 232 patients with PCA infarctions
      included in the registry. RESULTS: Infarctions of the ACA accounted for 1.3% of
      all cases of stroke (n = 3808) and 1.8% of cerebral infarctions (n = 2704).
      Stroke subtypes included cardioembolic infarction in 45.1% of patients,
      atherothrombotic infarction in 29.4%, lacunar infarct in 11.8%, infarct of
      unknown cause in 11.8% and infarction of unusual aetiology in 2%. In-hospital
      mortality was 7.8% (n = 4). Only 5 (9.8%) patients were symptom-free at hospital
      discharge. Speech disturbances (odds ratio [OR] = 0.48) and altered consciousness
      (OR = 0.31) were independent variables of ACA stroke in comparison with MCA
      infarction, whereas limb weakness (OR = 9.11), cardioembolism as stroke mechanism
      (OR = 2.49) and sensory deficit (OR = 0.35) were independent variables associated
      with ACA stroke in comparison with PCA infarction. CONCLUSION: Cardioembolism is
      the main cause of brain infarction in the territory of the ACA. Several clinical
      features are more frequent in stroke patients with ACA infarction than in
      patients with ischaemic stroke due to infarction in the MCA and PCA territories.

PMID- 19589133
TI  - Iterative refinement of structure-based sequence alignments by Seed Extension.
AB  - BACKGROUND: Accurate sequence alignment is required in many bioinformatics
      applications but, when sequence similarity is low, it is difficult to obtain
      accurate alignments based on sequence similarity alone. The accuracy improves
      when the structures are available, but current structure-based sequence alignment
      procedures still mis-align substantial numbers of residues. In order to correct
      such errors, we previously explored the possibility of replacing the residue
      based dynamic programming algorithm in structure alignment procedures with the
      Seed Extension algorithm, which does not use a gap penalty. Here, we describe a
      new procedure called RSE (Refinement with Seed Extension) that iteratively
      refines a structure-based sequence alignment. RESULTS: RSE uses SE (Seed
      Extension) in its core, which is an algorithm that we reported recently for
      obtaining a sequence alignment from two superimposed structures. The RSE
      procedure was evaluated by comparing the correctly aligned fractions of residues
      before and after the refinement of the structure-based sequence alignments
      produced by popular programs. CE, DaliLite, FAST, LOCK2, MATRAS, MATT, TM-align,
      SHEBA and VAST were included in this analysis and the NCBI's CDD root node set
      was used as the reference alignments. RSE improved the average accuracy of
      sequence alignments for all programs tested when no shift error was allowed. The
      amount of improvement varied depending on the program. The average improvements
      were small for DaliLite and MATRAS but about 5% for CE and VAST. More substantial
      improvements have been seen in many individual cases. The additional computation
      times required for the refinements were negligible compared to the times taken by
      the structure alignment programs. CONCLUSION: RSE is a computationally
      inexpensive way of improving the accuracy of a structure-based sequence
      alignment. It can be used as a standalone procedure following a regular structure
      based sequence alignment or to replace the traditional iterative refinement
      procedures based on residue-level dynamic programming algorithm in many structure
      alignment programs.

PMID- 19589134
TI  - Oocyte-granulosa-theca cell interactions during preantral follicular development.
AB  - The preantral-early antral follicle transition is the penultimate stage of
      follicular development in terms of gonadotropin dependence and follicle destiny
      (growth versus atresia). Follicular growth during this period is tightly
      regulated by oocyte-granulosa-theca cell interactions. Formation of the theca
      cell layer is a key event that occurs during this transitional stage. Granulosal
      factor(s) stimulates the recruitment of theca cells from cortical stromal cells,
      while oocyte-derived growth differentiation factor-9 (GDF-9) is involved in the
      differentiation of theca cells during this early stage of follicular development.
      The preantral to early antral transition is most susceptible to follicular
      atresia. GDF-9 promotes follicular survival and growth during transition from
      preantral stage to early antral stage by suppressing granulosa cell apoptosis and
      follicular atresia. GDF-9 also enhances preantral follicle growth by up
      regulating theca cell androgen production. Thecal factor(s) promotes granulosa
      cell proliferation and suppress granulosa cell apoptosis. Understanding the
      intraovarian mechanisms in the regulation of follicular growth and atresia during
      this stage may be of clinical significance in the selection of the best quality
      germ cells for assisted reproduction. In addition, since certain ovarian
      dysfunctions, such as polycystic ovarian syndrome and gonadotropin poor
      responsiveness, are consequences of dysregulated follicle growth at this
      transitional stage, understanding the molecular and cellular mechanisms in the
      control of follicular development during the preantral-early antral transition
      may provide important insight into the pathophysiology and rational treatment of
      these conditions.

PMID- 19589135
TI  - p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of
      796 archival specimens.
AB  - BACKGROUND: To evaluate the usefulness of this biomarker in the diagnosis of
      cases of cervical neoplasia we studied the immunohistochemical expression of
      p16INK4a in a large series of archival cervical biopsies arranged into tissue
      microarray format. METHODS: TMAs were constructed with tissue cores from archival
      formalin fixed, paraffin-embedded donor tissues from 796 patients, and included
      cases of cervical intraepithelial neoplasia (CIN)1 (n = 249), CIN2 (n = 233),
      CIN3 (n = 181), and invasive cervical carcinoma (n = 133). p16INK4a expression
      was scored using two different protocols: 1) positive vs negative p16INK4a
      staining; 2) a semi-quantitative immunohistochemical score (0 to 8 points)
      according to the intensity of staining and the proportion of stained cells
      RESULTS: p16INK4A expression was not seen in normal cervix tissue, but was found
      with increasing frequency in the sequence: CIN1 (180/249; 72.3%) - CIN2 (212/233;
      91.0%) - CIN3 (178/181; 98.3%) - invasive carcinoma (131/133; 98.5%). Using semi
      quantitative scoring, all normal cervical samples had low scores (from 0 to 2
      points), whilst the number of specimens with high scores was proportional to the
      degree of cervical dysplasia or the presence of invasive carcinoma. CONCLUSION:
      Immunohistochemical analysis of p16INK4a expression is a useful diagnostic tool.
      Expression is related to the degree of histological dysplasia, suggesting that it
      may have prognostic and predicative value in the management of cervical
      neoplasia.

PMID- 19589137
TI  - The role of VEGF-C/D and Flt-4 in the lymphatic metastasis of early-stage
      invasive cervical carcinoma.
AB  - BACKGROUND: To investigate the role of vascular endothelial growth factors (VEGF)
      C/D and their receptor Flt-4 in the lymphatic metastasis of early-stage invasive
      cervical carcinoma. METHODS: Immunohistochemical (IHC) staining with the
      antibodies against VEGF-C, VEGF-D, and Flt-4 was used to examine the expression
      of them in 97 cases of early-stage cervical carcinoma (Ia-IIa). Meanwhile, the
      lymphatic vessel density (LVD) was measured using the antibody against lymphatic
      vessel endothelial hyaluronan receptor-1 (LYVE-1). We then analyzed the
      correlation between Flt-4-positive vessel density (FVD), LVD and
      clinicopathological features of the tumors. RESULTS: (1) The positive rates of
      VEGF-C, VEGF-D, and Flt-4 were 57.7%, 60.8%, and 52.6% in the cervical tumor
      samples, respectively. (2) The expression levels of VEGF-C, VEGF-D, and Flt-4
      were significantly correlated with lymphatic metastasis and lymphatic vessel
      invasion. LVD was significantly associated with lymph node metastasis and
      lymphatic vessel invasion. On the other hand, FVD was strongly associated with
      clinical staging. (3) The expression levels of VEGF-C and VEGF-D were
      significantly correlated with LVD and FVD, while Flt-4 levels showed no
      correlation with LVD or FVD. CONCLUSION: VEGF-C/D and Flt-4 may play an important
      role in the process of lymphatic metastasis of early-stage invasive cervical
      carcinoma through paracrine and autocrine mechanisms.

PMID- 19589136
TI  - Stem cell and epithelial-mesenchymal transition markers are frequently
      overexpressed in circulating tumor cells of metastatic breast cancer patients.
AB  - INTRODUCTION: The persistence of circulating tumor cells (CTC) in breast cancer
      patients might be associated with stem cell like tumor cells which have been
      suggested to be the active source of metastatic spread in primary tumors.
      Furthermore, these cells also may undergo phenotypic changes, known as epithelial
      mesenchymal transition (EMT), which allows them to travel to the site of
      metastasis formation without getting affected by conventional treatment. Here we
      evaluated 226 blood samples of 39 metastatic breast cancer patients during a
      follow-up of palliative chemo-, antibody - or hormonal therapy for the expression
      of the stem cell marker ALDH1 and markers for EMT and correlated these findings
      with the presence of CTC and response to therapy. METHODS: 2 x 5 ml blood was
      analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of
      EpCAM, MUC-1 and HER2 transcripts. The recovered c-DNA was additionally multiplex
      tested for three EMT markers [Twist1, Akt2, PI3Kalpha] and separately for the
      tumor stem-cell markers ALDH1. The identification of EMT markers was considered
      positive if at least one marker was detected in the sample. RESULTS: 97% of 30
      healthy donor samples investigated were negative for EMT and 95% for ALDH1
      transcripts. CTC were detected in 69/226 (31%) cancer samples. In the CTC (+)
      group, 62% were positive for at least one of the EMT markers and 69% for ALDH1,
      respectively. In the CTC (-) group the percentages were 7% and 14%, respectively.
      In non-responders, EMT and ALDH1 expression was found in 62% and 44% of patients,
      in responders the rates were 10% and 5%, respectively. CONCLUSIONS: Our data
      indicate that a major proportion of CTC of metastatic breast cancer patients
      shows EMT and tumor stem cell characteristics. Further studies are needed to
      prove whether these markers might serve as an indicator for therapy resistant
      tumor cell populations and, therefore, an inferior prognosis.

PMID- 19589138
TI  - The role of genome and gene regulatory network canalization in the evolution of
      multi-trait polymorphisms and sympatric speciation.
AB  - BACKGROUND: Sexual reproduction has classically been considered as a barrier to
      the buildup of discrete phenotypic differentiation. This notion has been
      confirmed by models of sympatric speciation in which a fixed genetic architecture
      and a linear genotype phenotype mapping were assumed. In this paper we study the
      influence of a flexible genetic architecture and non-linear genotype phenotype
      map on differentiation under sexual reproduction.We use an individual based model
      in which organisms have a genome containing genes and transcription factor
      binding sites. Mutations involve single genes or binding sites or stretches of
      genome. The genome codes for a regulatory network that determines the gene
      expression pattern and hence the phenotype of the organism, resulting in a non
      linear genotype phenotype map. The organisms compete in a multi-niche
      environment, imposing selection for phenotypic differentiation. RESULTS: We find
      as a generic outcome the evolution of discrete clusters of organisms adapted to
      different niches, despite random mating. Organisms from different clusters are
      distinct on the genotypic, the network and the phenotypic level. However, the
      genome and network differences are constrained to a subset of the genome
      locations, a process we call genotypic canalization. We demonstrate how this
      canalization leads to an increased robustness to recombination and increasing
      hybrid fitness. Finally, in case of assortative mating, we explain how this
      canalization increases the effectiveness of assortativeness. CONCLUSION: We
      conclude that in case of a flexible genetic architecture and a non-linear
      genotype phenotype mapping, sexual reproduction does not constrain phenotypic
      differentiation, but instead constrains the genotypic differences underlying it.
      We hypothesize that, as genotypic canalization enables differentiation despite
      random mating and increases the effectiveness of assortative mating, sympatric
      speciation is more likely than is commonly suggested.

PMID- 19589139
TI  - Adiponectin, retinol-binding protein 4, and leptin in protracted critical illness
      of pulmonary origin.
AB  - INTRODUCTION: Critically ill patients requiring intensive care uniformly develop
      insulin resistance. This is most pronounced in patients with sepsis. Recently,
      several hormones secreted by adipose tissue have been identified to be involved
      in overall insulin sensitivity in metabolic syndrome-related conditions. However,
      little is known about these adipokines in critical illness. METHODS: We studied
      circulating levels of the adipokines adiponectin, retinol-binding protein 4
      (RBP4), and leptin during critical illness, and the impact of intensive insulin
      therapy, a therapy shown to affect insulin sensitivity, in serum samples from
      prolonged critically ill patients with a respiratory critical illness (n = 318).
      For comparison, we studied healthy subjects (n = 22) and acutely stressed
      patients (n = 22). RESULTS: During acute critical illness, circulating levels of
      adiponectin, RBP4, and leptin were low. Patients with sepsis had lower levels of
      leptin and RBP4 than did nonseptic patients. When critical illness was sustained,
      adipokine levels returned to normal reference values. Insulin therapy enhanced
      adiponectin, blunted the rise of RBP4, and did not alter leptin levels.
      CONCLUSIONS: Acute critical illness is associated with immediate, but transiently
      low serum adipokine levels. Adiponectin and RBP4 are associated with altered
      insulin resistance in critical illness.

PMID- 19589140
TI  - Determining the status of non-transferred embryos in Ireland: a conspectus of
      case law and implications for clinical IVF practice.
AB  - The development of in vitro fertilisation (IVF) as a treatment for human
      infertilty was among the most controversial medical achievements of the modern
      era. In Ireland, the fate and status of supranumary (non-transferred) embryos
      derived from IVF brings challenges both for clinical practice and public health
      policy because there is no judicial or legislative framework in place to address
      the medical, scientific, or ethical uncertainties. Complex legal issues exist
      regarding informed consent and ownership of embryos, particularly the use of non
      transferred embryos if a couple separates or divorces. But since case law is only
      beginning to emerge from outside Ireland and because legislation on IVF and human
      embryo status is entirely absent here, this matter is poised to raise
      contractual, constitutional and property law issues at the highest level. Our
      analysis examines this medico-legal challenge in an Irish context, and summarises
      key decisions on this issue rendered from other jurisdictions. The contractual
      issues raised by the Roche case regarding informed consent and the implications
      the initial judgment may have for future disputes over embryos are also
      discussed. Our research also considers a putative Constitutional 'right to
      procreate' and the implications EU law may have for an Irish case concerning the
      fate of frozen embryos. Since current Medical Council guidelines are insufficient
      to ensure appropriate regulation of the advanced reproductive technologies in
      Ireland, the report of the Commission on Assisted Human Reproduction is most
      likely to influence embryo custody disputes. Public policy requires the
      establishment and implementation of a more comprehensive legislative framework
      within which assisted reproductive medical services are offered.

PMID- 19589142
TI  - Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori
      seropositivity, gastric atrophy and gastric cancer in Japanese.
AB  - BACKGROUND: Previous studies have revealed the significance of Helicobacter
      pylori (H. pylori) infection as a risk factor of gastric cancer. Cytotoxin
      associated gene A (cagA) positivity has been demonstrated to determine the
      clinical outcome of H. pylori infection in the presence of SHP-2 (src homology 2
      domain-containing protein tyrosine phosphatase-2). This study aimed to examine
      the formerly reported association of G/A PTPN11 (protein-tyrosine phosphatase,
      nonreceptor-type 11) polymorphism (rs2301756) with gastric atrophy, as well as
      the association with gastric cancer in a Japanese population using a large sample
      size. METHODS: Study subjects were 583 histologically diagnosed patients with
      gastric cancer (429 males and 154 females) and age- and sex-frequency-matched
      1,636 non-cancer outpatients (1,203 males and 433 females), who visited Aichi
      Cancer Center Hospital between 2001-2005. Serum anti-H. pylori IgG antibody and
      pepsinogens were measured to evaluate H. pylori infection and gastric atrophy,
      respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated by a logistic model. RESULTS: Among H. pylori seropositive non-cancer
      outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI
      0.62-1.10, P = 0.194) for G/A, 0.84 (95% CI 0.39-1.81, P = 0.650) for A/A, and
      0.83 (95% CI 0.62-1.09, P = 0.182) for G/A+A/A, relative to G/G genotype, and
      that of severe gastric atrophy was 0.70 (95% CI 0.47-1.04, P = 0.079), 0.56 (95%
      CI 0.17-1.91, P = 0.356), and 0.68 (95% CI 0.46-1.01, P = 0.057), respectively.
      Among H. pylori infected subjects (H. pylori seropositive subjects and
      seronegative subjects with gastric atrophy), the adjusted OR of severe gastric
      atrophy was further reduced; 0.62 (95% CI 0.42-0.90, P = 0.012) for G/A+A/A. The
      distribution of the genotype in patients with gastric cancer was not
      significantly different from that for H. pylori infected subjects without gastric
      atrophy. CONCLUSION: Our study results revealed that those with the A/A genotype
      of PTPN11 rs2301756 polymorphism are at lower risk of severe gastric atrophy, but
      are not associated with a decreased risk of gastric cancer, which partially
      supported our previous finding that the polymorphism in the PTPN11 gene encoding
      SHP-2 was associated with the gastric atrophy risk in H. pylori infected
      Japanese. The biological roles of this PTPN11 polymorphism require further
      investigation.

PMID- 19589143
TI  - HIV/AIDS, parasites and co-infections: publication patterns in China.
AB  - BACKGROUND: Since its discovery, HIV/AIDS has arguably captured more attention
      among the Chinese biomedical research community than most other infectious
      diseases. Traditional parasitic diseases, on the other hand, are perceived as
      being increasingly neglected. However, it has long been recognized that
      interactions between HIV and other infective agents, including parasites,
      influence the health status of people living with HIV/AIDS. This study aimed at
      systematically reviewing the Chinese scientific literature on HIV/AIDS and
      parasites between 1986 and 2006 in order to substantiate or refute these claims,
      and to highlight neglected research areas. RESULTS: Searching the three largest
      Chinese scientific literature databases, in the China National Knowledge
      Infrastructure (CNKI) a total of 24,511 citations dealing with HIV/AIDS and
      15,398 parasite-specific publications were identified. Wanfang Data and VIP
      Information (VIP) contained 15,925 and 13,873 entries dealing with HIV/AIDS
      respectively, while 12,043 and 7,068 hits were scored when searching for
      parasitological references. The number of publications dealing with HIV/AIDS in
      China increased exponentially from 6 in 1986 to 3,372 in 2006 whereas the
      publication activity in the field of parasitology was more erratic and lately
      started to decline. Epidemiology was the most-reported field of endeavor,
      accounting for 26.0% and 24.6% of the HIV/AIDS and parasitological literature,
      respectively, while publications dealing with health education only represented
      2.9% and 0.7% of all publications, respectively. The total number of Chinese
      articles focusing on HIV/AIDS and parasite co-infection was 650, with large year
      on-year differences in publication numbers. The single-most frequently studied
      system was HIV-Pneumocystis carinii co-infection. CONCLUSION: The present study
      revealed that in China, the fields of parasitic diseases, especially
      opportunistic parasitic infections linked with HIV/AIDS, is increasingly
      neglected. This suggests a need to enhance research in the field of opportunistic
      parasitic infections and parasitology in general.

PMID- 19589141
TI  - Motif composition, conservation and condition-specificity of single and
      alternative transcription start sites in the Drosophila genome.
AB  - BACKGROUND: Transcription initiation is a key component in the regulation of gene
      expression. mRNA 5' full-length sequencing techniques have enhanced our
      understanding of mammalian transcription start sites (TSSs), revealing different
      initiation patterns on a genomic scale. RESULTS: To identify TSSs in Drosophila
      melanogaster, we applied a hierarchical clustering strategy on available 5'
      expressed sequence tags (ESTs) and identified a high quality set of 5,665 TSSs
      for approximately 4,000 genes. We distinguished two initiation patterns: 'peaked'
      TSSs, and 'broad' TSS cluster groups. Peaked promoters were found to contain
      location-specific sequence elements; conversely, broad promoters were associated
      with non-location-specific elements. In alignments across other Drosophila
      genomes, conservation levels of sequence elements exceeded 90% within the
      melanogaster subgroup, but dropped considerably for distal species. Elements in
      broad promoters had lower levels of conservation than those in peaked promoters.
      When characterizing the distributions of ESTs, 64% of TSSs showed distinct
      associations to one out of eight different spatiotemporal conditions. Available
      whole-genome tiling array time series data revealed different temporal patterns
      of embryonic activity across the majority of genes with distinct alternative
      promoters. Many genes with maternally inherited transcripts were found to have
      alternative promoters utilized later in development. Core promoters of maternally
      inherited transcripts showed differences in motif composition compared to
      zygotically active promoters. CONCLUSIONS: Our study provides a comprehensive map
      of Drosophila TSSs and the conditions under which they are utilized. Distinct
      differences in motif associations with initiation pattern and spatiotemporal
      utilization illustrate the complex regulatory code of transcription initiation.

PMID- 19589144
TI  - An updated atlas of human helminth infections: the example of East Africa.
AB  - BACKGROUND: Reliable and updated maps of helminth (worm) infection distributions
      are essential to target control strategies to those populations in greatest need.
      Although many surveys have been conducted in endemic countries, the data are
      rarely available in a form that is accessible to policy makers and the managers
      of public health programmes. This is especially true in sub-Saharan Africa, where
      empirical data are seldom in the public domain. In an attempt to address the
      paucity of geographical information on helminth risk, this article describes the
      development of an updated global atlas of human helminth infection, showing the
      example of East Africa. METHODS: Empirical, cross-sectional estimates of
      infection prevalence conducted since 1980 were identified using electronic and
      manual search strategies of published and unpublished sources. A number of
      inclusion criteria were imposed for identified information, which was extracted
      into a standardized database. Details of survey population, diagnostic methods,
      sample size and numbers infected with schistosomes and soil-transmitted helminths
      were recorded. A unique identifier linked each record to an electronic copy of
      the source document, in portable document format. An attempt was made to identify
      the geographical location of each record using standardized geolocation
      procedures and the assembled data were incorporated into a geographical
      information system. RESULTS: At the time of writing, over 2,748 prevalence
      surveys were identified through multiple search strategies. Of these, 2,612 were
      able to be geolocated and mapped. More than half (58%) of included surveys were
      from grey literature or unpublished sources, underlining the importance of
      reviewing in-country sources. 66% of all surveys were conducted since 2000.
      Comprehensive, countrywide data are available for Burundi, Rwanda and Uganda. In
      contrast, information for Kenya and Tanzania is typically clustered in specific
      regions of the country, with few records from areas with very low population
      density and/or environmental conditions which are unfavourable for helminth
      transmission. Information is presented on the prevalence and geographical
      distribution for the major helminth species. CONCLUSION: For all five countries,
      the information assembled in the current atlas provides the most reliable, up-to
      date and comprehensive source of data on the distribution of common helminth
      infections to guide the rational implementation of control efforts.

PMID- 19589145
TI  - The effects of crisis plans for patients with psychotic and bipolar disorders: a
      randomised controlled trial.
AB  - BACKGROUND: Crises and (involuntary) admissions have a strong impact on patients
      and their caregivers. In some countries, including the Netherlands, the number of
      crises and (involuntary) admissions have increased in the last years. There is
      also a lack of effective interventions to prevent their occurrence. Previous
      research has shown that a form of psychiatric advance statement - joint crisis
      plan - may prevent involuntary admissions, but another study showed no
      significant results for another form. The question remains which form of
      psychiatric advance statement may help to prevent crisis situations. This study
      examines the effects of two other psychiatric advance statements. The first is
      created by the patient with help from a patient's advocate (Patient Advocate
      Crisis Plan: PACP) and the second with the help of a clinician only (Clinician
      facilitated Crisis Plan: CCP). We investigate whether patients with a PACP or CCP
      show fewer emergency visits and (involuntary) admissions as compared to patients
      without a psychiatric advance statement. Furthermore, this study seeks to
      identify possible mechanisms responsible for the effects of a PACP or a CCP.
      METHODS/DESIGN: This study is a randomised controlled trial with two intervention
      groups and one control condition. Both interventions consist of a crisis plan,
      facilitated through the patient's advocate or the clinician
      respectively.Outpatients with psychotic or bipolar disorders, who experienced at
      least one psychiatric crisis during the previous two years, are randomly
      allocated to one of the three groups. Primary outcomes are the number of
      emergency (after hour) visits, (involuntary) admissions and the length of stay in
      hospital. Secondary outcomes include psychosocial functioning and treatment
      satisfaction. The possible mediator variables of the effects of the crisis plans
      are investigated by assessing the patient's involvement in the creation of the
      crisis plan, working alliance, insight into illness, recovery style, social
      support, locus of control, service engagement and coping with crises situations.
      The interviews take place before randomisation, nine month later and finally
      eighteen months after randomisation. DISCUSSION: This study examines the effects
      of two types of crisis plans. In addition, the results offer an understanding of
      the way these advance statements work and whether it is more effective to include
      a patients' advocate in the process of creating a psychiatric advance statement.
      These statements may be an intervention to prevent crises and the use of
      compulsion in mental health care. The strength and limitations of this study are
      discussed. TRIAL REGISTRATION: Current Controlled Trails NTR1166.

PMID- 19589146
TI  - Early effects of oral administration of lafutidine with mosapride compared with
      lafutidine alone on intragastric pH values.
AB  - BACKGROUND: The ideal medication for treatment of acid related diseases should
      have a rapid onset of action to promote hemostasis and resolution of symptoms.
      The aim of our study was to investigate the inhibitory effects on gastric acid
      secretion after a single oral administrations of lafutidine, is a newly
      synthesized H2-receptor antagonist, with mosapride 5 mg or lafutidine alone.
      METHODS: Ten Helicobacter pylori negative male subjects participated in this
      randomized, two-way crossover study. Intragastric pH was monitored continuously
      for 4 hours after a single oral administration of lafutidine 10 mg or lafutidine
      10 mg with mosapride 5 mg (the lafutidine being administrated one hour after the
      mosapride). Each administration was separated by a 7-day washout period. RESULTS:
      The average pH during the 4-hour period after administration of lafutidine 10 mg
      with mosapride 5 mg was higher than after lafutidine 10 mg alone (median: 5.25
      versus 4.58, respectively; p = 0.0318). During the 3-4 hour study period,
      lafutidine 10 mg with mosapride 5 mg provided a higher pH, compared to lafutidine
      10 mg alone (median: 7.28 versus 6.42; p = 0.0208). CONCLUSION: In H. pylori
      negative healthy male subjects, an oral dose of lafutidine 10 mg with mosapride 5
      mg more rapidly increased intragastric pH than lafutidine 10 mg alone.

PMID- 19589147
TI  - Hmrbase: a database of hormones and their receptors.
AB  - BACKGROUND: Hormones are signaling molecules that play vital roles in various
      life processes, like growth and differentiation, physiology, and reproduction.
      These molecules are mostly secreted by endocrine glands, and transported to
      target organs through the bloodstream. Deficient, or excessive, levels of
      hormones are associated with several diseases such as cancer, osteoporosis,
      diabetes etc. Thus, it is important to collect and compile information about
      hormones and their receptors. DESCRIPTION: This manuscript describes a database
      called Hmrbase which has been developed for managing information about hormones
      and their receptors. It is a highly curated database for which information has
      been collected from the literature and the public databases. The current version
      of Hmrbase contains comprehensive information about approximately 2000 hormones,
      e.g., about their function, source organism, receptors, mature sequences,
      structures etc. Hmrbase also contains information about approximately 3000
      hormone receptors, in terms of amino acid sequences, subcellular localizations,
      ligands, and post-translational modifications etc. One of the major features of
      this database is that it provides data about approximately 4100 hormone-receptor
      pairs. A number of online tools have been integrated into the database, to
      provide the facilities like keyword search, structure-based search, mapping of a
      given peptide(s) on the hormone/receptor sequence, sequence similarity search.
      This database also provides a number of external links to other
      resources/databases in order to help in the retrieving of further related
      information. CONCLUSION: Owing to the high impact of endocrine research in the
      biomedical sciences, the Hmrbase could become a leading data portal for
      researchers. The salient features of Hmrbase are hormone-receptor pair-related
      information, mapping of peptide stretches on the protein sequences of hormones
      and receptors, Pfam domain annotations, categorical browsing options, online data
      submission, DrugPedia linkage etc. Hmrbase is available online for public from
      http://crdd.osdd.net/raghava/hmrbase/.

PMID- 19589149
TI  - Effect of lactoperoxidase on the antimicrobial effectiveness of the thiocyanate
      hydrogen peroxide combination in a quantitative suspension test.
AB  - BACKGROUND: The positive antimicrobial effects of increasing concentrations of
      thiocyanate (SCN-) and H2O2 on the human peroxidase defence system are well
      known. However, little is known about the quantitative efficacy of the human
      peroxidase thiocyanate H2O2 system regarding Streptococcus mutans and sanguinis,
      as well as Candida albicans. The aim of this study was to evaluate the effect of
      the enzyme lactoperoxidase on the bactericidal and fungicidal effectiveness of a
      thiocyanate-H2O2 combination above the physiological saliva level. To evaluate
      the optimal effectiveness curve, the exposure times were restricted to 1, 3, 5,
      and 15 min. RESULTS: The bactericidal and fungicidal effects of lactoperoxidase
      on Streptococcus mutans and sanguinis and Candida albicans were evaluated by
      using two test mixtures of a 2.0% (w/v; 0.34 M) thiocyanate and 0.4% (w/v; 0.12
      M) hydrogen peroxide solution, one without and one with lactoperoxidase.
      Following the quantitative suspension tests (EN 1040 and EN 1275), the growth of
      surviving bacteria and fungi in a nutrient broth was measured. The reduction
      factor in the suspension test without lactoperoxidase enzyme was < 1 for all
      three tested organisms. Thus, the mixtures of 2.0% (w/v; 0.34 M) thiocyanate and
      0.4% (w/v; 0.12 M) hydrogen peroxide had no in vitro antimicrobial effect on
      Streptococcus mutans and sanguinis or Candida albicans. However, the suspension
      test with lactoperoxidase showed a high bactericidal and fungicidal effectiveness
      in vitro. CONCLUSION: The tested thiocyanate and H2O2 mixtures showed no relevant
      antimicrobial effect. However, by adding lactoperoxidase enzyme, the mixtures
      became not only an effective bactericidal (Streptococcus mutans and sanguinis)
      but also a fungicidal (Candida albicans) agent.

PMID- 19589150
TI  - Current role of surgery in small cell lung carcinoma.
AB  - Small cell lung carcinoma represents 15-20% of lung cancer. Is is characterized
      by rapid growth and early disseminated disease with poor outcome. For many years
      surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since
      radiotherapy and chemoradiotherapy were found to be more efficient in the
      management of these patients. Never the less some surgeons continue to be in
      favor of surgery as part of a combined modality treatment in patients with SCLC.
      The reevaluation of the role of surgery in this group of patients is based on
      clinical data indicating a much better prognosis in selected patients with
      limited disease (T1-2, N0, M0), the high rate of local recurrence after
      chemoradiotherapy with surgery considered eventually more efficient in the local
      control of the disease and the fact that surgery is the most accurate tool to
      access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and
      treat the Non Small Cell Lung Cancer component of mixed tumors. Performing
      surgery for local disease SCLC requires a complete preoperative assessment to
      exclude the presence of nodal involvement. In stage I surgery must always be
      followed by adjuvant chemotherapy, while in stage II and III surgery must be
      planned only in the context of clinical trials and after a pathologic response to
      induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation
      should be used to reduce the incidence of brain metastasis.

PMID- 19589148
TI  - Comparison of wall thickening and ejection fraction by cardiovascular magnetic
      resonance and echocardiography in acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to compare cardiovascular magnetic
      resonance (CMR) and echocardiography (echo) in patients treated with primary
      percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI)
      with emphasis on the analysis of left ventricular function and left ventricular
      wall motion characteristics. METHODS: We performed CMR and echo in 52 patients
      with first AMI shortly after primary angioplasty and four months thereafter. CMR
      included cine-MR and T1-weighted first-pass and late-gadolinium enhancement (LGE)
      sequences. Global ejection fraction (EF(CMR), %) and regional left ventricular
      function (systolic wall thickening %, [SWT]) were determined from cine-MR images.
      In echo the global left ventricular function (EF(echo), %) and regional wall
      motion abnormalities were determined. A segment in echo was scored as "infarcted"
      if it was visually > 50% hypokinetic. RESULTS: EF(echo) revealed a poor
      significant agreement with EF(CMR) at baseline (r: 0.326; p < 0.01) but higher
      correlation at follow-up (r: 0.479; p < 0.001). The number of infarcted segments
      in echocardiography correlated best with the number of segments which showed
      systolic wall thickening < 30% (r: 0.498; p < 0.001) at baseline and (r: 0.474; p
      < 0.001) at follow-up. Improvement of EF was detected in both CMR and
      echocardiography increasing from 44.2 +/- 11.6% to 49.2 +/- 11% (p < 0.001) by
      CMR and from 51.2 +/- 8.1% to 54.5 +/- 8.3% (p < 0.001) by echocardiography.
      CONCLUSION: Wall motion and EF by CMR and echocardiography correlate poorly in
      the acute stage of myocardial infarction. Correlation improves after four months.
      Systolic wall thickening by CMR < 30% indicates an infarcted segment with
      influence on the left ventricular function.

PMID- 19589151
TI  - Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis
      and autoimmune thyroid diseases.
AB  - INTRODUCTION: The majority of autoimmune diseases such as rheumatoid arthritis
      (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking
      female predominance superimposed on a predisposing genetic background. The role
      of extremely skewed X-chromosome inactivation (XCI) has been questioned in the
      pathogenesis of several autoimmune diseases. METHODS: We examined XCI profiles of
      females affected with RA (n = 106), AITDs (n = 145) and age-matched healthy women
      (n = 257). XCI analysis was performed by enzymatic digestion of DNA with a
      methylation sensitive enzyme (HpaII) followed by PCR of a polymorphic CAG repeat
      in the androgen receptor (AR) gene. The XCI pattern was classified as skewed when
      80% or more of the cells preferentially inactivated the same X-chromosome.
      RESULTS: Skewed XCI was observed in 26 of the 76 informative RA patients (34.2%),
      26 of the 100 informative AITDs patients (26%), and 19 of the 170 informative
      controls (11.2%) (P < 0.0001; P = 0.0015, respectively). More importantly,
      extremely skewed XCI, defined as > 90% inactivation of one allele, was present in
      17 RA patients (22.4%), 14 AITDs patients (14.0%), and in only seven controls
      (4.1%, P < 0.0001; P = 0.0034, respectively). Stratifying RA patients according
      to laboratory profiles (rheumatoid factor and anti-citrullinated protein
      antibodies), clinical manifestations (erosive disease and nodules) and the
      presence of others autoimmune diseases did not reveal any statistical
      significance (P > 0.05). CONCLUSIONS: These results suggest a possible role for
      XCI mosaicism in the pathogenesis of RA and AITDs and may in part explain the
      female preponderance of these diseases.

PMID- 19589152
TI  - Proteins involved in difference of sorbitol fermentation rates of the toxigenic
      and nontoxigenic Vibrio cholerae El Tor strains revealed by comparative proteome
      analysis.
AB  - BACKGROUND: The nontoxigenic V. cholerae El Tor strains ferment sorbitol faster
      than the toxigenic strains, hence fast-fermenting and slow-fermenting strains are
      defined by sorbitol fermentation test. This test has been used for more than 40
      years in cholera surveillance and strain analysis in China. Understanding of the
      mechanisms of sorbitol metabolism of the toxigenic and nontoxigenic strains may
      help to explore the genome and metabolism divergence in these strains. Here we
      used comparative proteomic analysis to find the proteins which may be involved in
      such metabolic difference. RESULTS: We found the production of formate and lactic
      acid in the sorbitol fermentation medium of the nontoxigenic strain was earlier
      than of the toxigenic strain. We compared the protein expression profiles of the
      toxigenic strain N16961 and nontoxigenic strain JS32 cultured in sorbitol
      fermentation medium, by using fructose fermentation medium as the control.
      Seventy-three differential protein spots were found and further identified by
      MALDI-MS. The difference of product of fructose-specific IIA/FPR component gene
      and mannitol-1-P dehydrogenase, may be involved in the difference of sorbitol
      transportation and dehydrogenation in the sorbitol fast- and slow-fermenting
      strains. The difference of the relative transcription levels of pyruvate formate
      lyase to pyruvate dehydrogenase between the toxigenic and nontoxigenic strains
      may be also responsible for the time and ability difference of formate production
      between these strains. CONCLUSION: Multiple factors involved in different
      metabolism steps may affect the sorbitol fermentation in the toxigenic and
      nontoxigenic strains of V. cholerae El Tor.

PMID- 19589153
TI  - Genomic profiling distinguishes familial multiple and sporadic multiple
      meningiomas.
AB  - BACKGROUND: Meningiomas may occur either as familial tumors in two distinct
      disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or
      sporadically, as either single or multiple tumors in individuals with no family
      history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve
      inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome
      22q. This study was undertaken to establish whether genomic profiling could
      distinguish familial multiple meningiomas from sporadic solitary and sporadic
      multiple meningiomas. METHODS: We compared 73 meningiomas presenting as sporadic
      solitary (64), sporadic multiple (5) and familial multiple (4) tumors using
      genomic profiling by array comparative genomic hybridization (array CGH).
      RESULTS: Sporadic solitary meningiomas revealed genomic rearrangements consistent
      with at least two mechanisms of tumor initiation, as unsupervised cluster
      analysis readily distinguished tumors with chromosome 22 deletion (associated
      with loss of the NF2 tumor suppressor) from those without chromosome 22 deletion.
      Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer
      chromosomal imbalance events overall, tumors with chromosome 22 deletion further
      clustered into two major groups that largely, though not perfectly, matched with
      their benign (WHO Grade I) or advanced (WHO Grades II and III) histological
      grade, with the latter exhibiting a significantly greater degree of genomic
      imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of
      genomic imbalance events comparable to the atypical grade solitary tumors. By
      contrast, familial multiple meningiomas displayed no imbalances, supporting a
      distinct mechanism for the origin for these tumors. CONCLUSION: Genomic profiling
      can provide an unbiased adjunct to traditional meningioma classification and
      provides a basis for exploring the different genetic underpinnings of tumor
      initiation and progression. Most importantly, the striking difference observed
      between sporadic and familial multiple meningiomas indicates that genomic
      profiling can provide valuable information for differential diagnosis of subjects
      with multiple meningiomas and for considering the risk for tumor occurrence in
      their family members.

PMID- 19589154
TI  - Assessment of dietary intake among pregnant women in a rural area of western
      China.
AB  - BACKGROUND: Adequate maternal nutrient intake during pregnancy is important to
      ensure satisfactory birth outcomes. There are no data available on the usual
      dietary intake among pregnant women in rural China. The present study describes
      and evaluates the dietary intake in a cohort of pregnant women living in two
      counties of rural Shaanxi, western China. METHODS: 1420 pregnant women were
      recruited from a trial that examined the effects of micronutrient supplementation
      on birth outcomes. Dietary information was collected at the end of their
      trimester or after delivery with an interviewed-administrated semi-quantitative
      food frequency questionnaire (FFQ). Nutrients intake was calculated from the FFQ
      and compared to the Estimated Average Requirements (EAR). The EAR cut-offs based
      on the Chinese Nutrition Society Dietary Reference Intakes (DRIs) were used to
      assess the prevalence of inadequate dietary intakes of energy, protein, calcium,
      zinc, riboflavin, vitamin C and folate. Mann-Whitney U and Kruskal Wallis tests
      were used to compare nutrient intakes across subgroups. RESULTS: The mean
      nutrient intakes assessed by the FFQ was similar to those reported in the 2002
      Chinese National Nutrition and Health Survey from women living in rural areas
      except for low intakes of protein, fat, iron and zinc. Of the participants, 54%
      were at risk of inadequate intake of energy. There were high proportions of
      pregnant women who did not have adequate intakes of folate (97%) and zinc (91%).
      Using the "probability approach", 64% of subjects had an inadequate consumption
      of iron. CONCLUSION: These results reveal that the majority of pregnant women in
      these two counties had low intakes of nutrients that are essential for pregnancy
      such as iron and folate. TRIAL REGISTRATION: ISRCTN08850194.

PMID- 19589155
TI  - puma: a Bioconductor package for propagating uncertainty in microarray analysis.
AB  - BACKGROUND: Most analyses of microarray data are based on point estimates of
      expression levels and ignore the uncertainty of such estimates. By determining
      uncertainties from Affymetrix GeneChip data and propagating these uncertainties
      to downstream analyses it has been shown that we can improve results of
      differential expression detection, principal component analysis and clustering.
      Previously, implementations of these uncertainty propagation methods have only
      been available as separate packages, written in different languages. Previous
      implementations have also suffered from being very costly to compute, and in the
      case of differential expression detection, have been limited in the experimental
      designs to which they can be applied. RESULTS: puma is a Bioconductor package
      incorporating a suite of analysis methods for use on Affymetrix GeneChip data.
      puma extends the differential expression detection methods of previous work from
      the 2-class case to the multi-factorial case. puma can be used to automatically
      create design and contrast matrices for typical experimental designs, which can
      be used both within the package itself but also in other Bioconductor packages.
      The implementation of differential expression detection methods has been
      parallelised leading to significant decreases in processing time on a range of
      computer architectures. puma incorporates the first R implementation of an
      uncertainty propagation version of principal component analysis, and an
      implementation of a clustering method based on uncertainty propagation. All of
      these techniques are brought together in a single, easy-to-use package with
      clear, task-based documentation. CONCLUSION: For the first time, the puma package
      makes a suite of uncertainty propagation methods available to a general audience.
      These methods can be used to improve results from more traditional analyses of
      microarray data. puma also offers improvements in terms of scope and speed of
      execution over previously available methods. puma is recommended for anyone
      working with the Affymetrix GeneChip platform for gene expression analysis and
      can also be applied more generally.

PMID- 19589156
TI  - Genetic specificity and potential for local adaptation between dengue viruses and
      mosquito vectors.
AB  - BACKGROUND: Several observations support the hypothesis that vector-driven
      selection plays an important role in shaping dengue virus (DENV) genetic
      diversity. Clustering of DENV genetic diversity at a particular location may
      reflect underlying genetic structure of vector populations, which combined with
      specific vector genotype x virus genotype (G x G) interactions may promote
      adaptation of viral lineages to local mosquito vector genotypes. Although spatial
      structure of vector polymorphism at neutral genetic loci is well-documented,
      existence of G x G interactions between mosquito and virus genotypes has not been
      formally demonstrated in natural populations. Here we measure G x G interactions
      in a system representative of a natural situation in Thailand by challenging
      three isofemale families from field-derived Aedes aegypti with three
      contemporaneous low-passage isolates of DENV-1. RESULTS: Among indices of vector
      competence examined, the proportion of mosquitoes with a midgut infection, viral
      RNA concentration in the body, and quantity of virus disseminated to the
      head/legs (but not the proportion of infected mosquitoes with a disseminated
      infection) strongly depended on the specific combinations of isofemale families
      and viral isolates, demonstrating significant G x G interactions. CONCLUSION:
      Evidence for genetic specificity of interactions in our simple experimental
      design indicates that vector competence of Ae. aegypti for DENV is likely
      governed to a large extent by G x G interactions in genetically diverse, natural
      populations. This result challenges the general relevance of conclusions from
      laboratory systems that consist of a single combination of mosquito and DENV
      genotypes. Combined with earlier evidence for fine-scale genetic structure of
      natural Ae. aegypti populations, our finding indicates that the necessary
      conditions for local DENV adaptation to mosquito vectors are met.

PMID- 19589157
TI  - Characteristics of inmates witnessing overdose events in prison: implications for
      prevention in the correctional setting.
AB  - BACKGROUND: Although prevention of opiate overdose has been gaining attention as
      a harm reduction measure with community drug users, there is scarce information
      about drug overdose in prison. In correctional institutions without a drug free
      environment, awareness of overdose events is an important public health concern.
      This study explores the frequency with which inmates in a state penitentiary
      system report having witnessed drug overdose events in prison. It also explores
      whether participants who have witnessed an overdose in prison and know someone
      who died from an overdose in prison significantly differ from those that do not
      in selected sociodemographic variables and drug use history to identify a target
      population for prevention interventions. METHODS: Data comes from a cross
      sectional survey of sentenced inmates in the state prisons of Puerto Rico. A
      complex probabilistic, multistage sampling design was used. A total of 1,179
      individuals participated for an 89% response rate. RESULTS: Factors associated
      with witnessing an overdose event in prison include: male sex, age 25 or older,
      drug use during current incarceration, and drug injection in prison. Factors
      associated with knowing someone who died from an overdose in prison include: male
      sex, age between 25-35, previous incarcerations, and drug use during current
      incarceration. CONCLUSION: Witnessing a drug overdose is a frequent occurrence
      within the prison system. The likelihood of witnessing an overdose is greater
      with being male, polydrug use and drug injection in prison. Findings signal an
      urgent public health challenge that requires prompt interventions to reduce this
      drug related harm within the correctional system, including adequate access to
      medication with opiate agonists.

PMID- 19589158
TI  - Error statistics of hidden Markov model and hidden Boltzmann model results.
AB  - BACKGROUND: Hidden Markov models and hidden Boltzmann models are employed in
      computational biology and a variety of other scientific fields for a variety of
      analyses of sequential data. Whether the associated algorithms are used to
      compute an actual probability or, more generally, an odds ratio or some other
      score, a frequent requirement is that the error statistics of a given score be
      known. What is the chance that random data would achieve that score or better?
      What is the chance that a real signal would achieve a given score threshold?
      RESULTS: Here we present a novel general approach to estimating these false
      positive and true positive rates that is significantly more efficient than are
      existing general approaches. We validate the technique via an implementation
      within the HMMER 3.0 package, which scans DNA or protein sequence databases for
      patterns of interest, using a profile-HMM. CONCLUSION: The new approach is faster
      than general naive sampling approaches, and more general than other current
      approaches. It provides an efficient mechanism by which to estimate error
      statistics for hidden Markov model and hidden Boltzmann model results.

PMID- 19589160
TI  - Foot orthoses: how much customisation is necessary?
AB  - The relative merit of customised versus prefabricated foot orthoses continues to
      be the subject of passionate debate among foot health professionals. Although
      there is currently insufficient evidence to reach definitive conclusions, a
      growing body of research literature suggests that prefabricated foot orthoses may
      produce equivalent clinical outcomes to customised foot orthoses for some
      conditions. Consensus guidelines for the prescription of customised foot orthoses
      need to be developed so that the hypothesised benefits of these devices can be
      thoroughly evaluated.

PMID- 19589161
TI  - The Brief Fear of Negative Evaluation Scale (BFNE): translation and validation
      study of the Iranian version.
AB  - BACKGROUND: The Brief Fear of Negative Evaluation Scale (BFNE) is a commonly used
      instrument to measure social anxiety. This study aimed to translate and to test
      the reliability and validity of the BFNE in Iran. METHODS: The English language
      version of the BFNE was translated into Persian (Iranian language) and was used
      in this study. The questionnaire was administered to a consecutive sample of 235
      students with (n = 33, clinical group) and without social phobia (n = 202, non
      clinical group). In addition to the BFNE, two standard instruments were used to
      measure social phobia severity: the Social Phobia Inventory (SPIN), and the
      Social Interaction Anxiety Scale (SIAS). All participants completed a brief
      background information questionnaire, the SPIN, the SIAS and the BFNE scales.
      Statistical analysis was performed to test the reliability and validity of the
      BFNE. RESULTS: In all 235 students were studied (111 male and 124 female). The
      mean age for non-clinical group was 22.2 (SD = 2.1) years and for clinical sample
      it was 22.4 (SD = 1.8) years. Cronbach's alpha coefficient (to test reliability)
      was acceptable for both non-clinical and clinical samples (alpha = 0.90 and 0.82
      respectively). In addition, 3-week test-retest reliability was performed in non
      clinical sample and the intraclass correlation coefficient (ICC) was quite high
      (ICC = 0.71). Validity as performed using convergent and discriminant validity
      showed satisfactory results. The questionnaire correlated well with established
      measures of social phobia such as the SPIN (r = 0.43, p < 0.001) and the SIAS (r
      = 0.54, p < 0.001). Also the BFNE discriminated well between men and women with
      and without social phobia in the expected direction. Factor analysis supported a
      two-factor solution corresponding to positive and reverse-worded items.
      CONCLUSION: This validation study of the Iranian version of BFNE proved that it
      is an acceptable, reliable and valid measure of social phobia. However, since the
      scale showed a two-factor structure and this does not confirm to the theoretical
      basis for the BFNE, thus we suggest the use of the BFNE-II when it becomes
      available in Iran. The validation study of the BFNE-II is in progress.

PMID- 19589159
TI  - Genomic profiling of breast tumours in relation to BRCA abnormalities and
      phenotypes.
AB  - INTRODUCTION: Germline mutations in the BRCA1 and BRCA2 genes account for a
      considerable fraction of familial predisposition to breast cancer. Somatic
      mutations in BRCA1 and BRCA2 have not been found and the involvement of these
      genes in sporadic tumour development therefore remains unclear. METHODS: The
      study group consisted of 67 primary breast tumours with and without BRCA1 or
      BRCA2 abnormalities. Genomic alterations were profiled by high-resolution (~7
      kbp) comparative genome hybridisation (CGH) microarrays. Tumour phenotypes were
      analysed by immunohistochemistry on tissue microarrays using selected biomarkers
      (ER, PR, HER-2, EGFR, CK5/6, CK8, CK18). RESULTS: Classification of genomic
      profiles through cluster analysis revealed four subgroups, three of which
      displayed high genomic instability indices (GII). Two of these GII-high subgroups
      were enriched with either BRCA1- or BRCA2-related tumours whereas the third was
      not BRCA-related. The BRCA1-related subgroup mostly displayed non-luminal
      phenotypes, of which basal-like were most prominent, whereas the other two
      genomic instability subgroups BRCA2- and GII-high-III (non-BRCA), were almost
      entirely of luminal phenotype. Analysis of genome architecture patterns revealed
      similarities between the BRCA1- and BRCA2 subgroups, with long deletions being
      prominent. This contrasts with the third instability subgroup, not BRCA-related,
      where small gains were more prominent. CONCLUSIONS: The results suggest that
      BRCA1- and BRCA2-related tumours develop largely through distinct genetic
      pathways in terms of the regions altered while also displaying distinct
      phenotypes. Importantly, we show that the development of a subset of sporadic
      tumours is similar to that of either familial BRCA1- or BRCA2 tumours. Despite
      their differences, we observed clear similarities between the BRCA1- and BRCA2
      related subgroups reflected in the type of genomic alterations acquired with
      deletions of long DNA segments being prominent. This suggests similarities in the
      mechanisms promoting genomic instability for BRCA1- and BRCA2-associated tumours,
      possibly relating to deficiency in DNA repair through homologous recombination.
      Indeed, this feature characterized both familial and sporadic tumours displaying
      BRCA1- or BRCA2-like spectrums of genomic alterations. The importance of these
      findings lies in the potential benefit from targeted therapy, through the use of
      agents leading to DNA double-strand breaks such as PARP inhibitors (olaparib) and
      cisplatin, for a much larger group of patients than the few BRCA1 and BRCA2
      germline mutation carriers.

PMID- 19589162
TI  - Possible roles of Epstein-Barr virus in Castleman disease.
AB  - BACKGROUND: Complete resection seemed to be curative in patients with Castleman
      disease of any location but the disease is likely to be reactive in its
      pathogenesis. The relation between Epstein-Barr virus and Castleman disease has
      not been elucidated. We tried to define the role of Epstein-Barr virus in the
      pathogenesis of Castleman disease. METHODS: 20 cases of Castleman disease were
      retrospectively reviewed from 1993 to 2006. At least 2 to 4 representative
      sections of formalin-fixed, paraffin-embedded specimens from each patient were
      obtained to examine the presence of EBV and its localization by hematoxylin-eosin
      stain, immunohistochemistry, polymerase chain reaction and In-situ hybridization
      RESULTS: Hyaline-vascular type was diagnosed in 18 cases, plasma cell type in 1
      and mixed type in 1 case. All of them were positive for Epstein-Barr virus
      confirmed by PCR. For tumors that EBER(Epstein-Barr early region) signals mainly
      localized in the germinal centers have increased vascularity than cases with EBER
      detected in inter-follicular areas. CONCLUSION: There is a strong association
      between Castleman disease and Epstein-Barr virus. EBV may have a potential role
      in angiogenesis of Castleman disease. For smaller lesion with high activity of
      angiogenesis but not amenable for curative resection, anti-angiogenesis
      medications may have a potential role to control the disease.

PMID- 19589164
TI  - Knowledge and utilization of intermittent preventive treatment for malaria among
      pregnant women attending antenatal clinics in primary health care centers in
      rural southwest, Nigeria: a cross-sectional study.
AB  - BACKGROUND: Intermittent preventive treatment for prevention of malaria in
      pregnancy (IPTp) is a key component of malaria control strategy in Nigeria and
      sulfadoxine-pyrimethamine (SP) is the drug of choice. Despite the evidence of the
      effectiveness of IPTp strategy using SP in reducing the adverse effects of
      malaria during pregnancy the uptake and coverage in Nigeria is low. This study
      set out to assess the use of IPTp among pregnant women attending primary health
      centres in the rural area and determine factors that influence the uptake.
      METHODS: A cross-sectional study was carried out between July and August 2007
      among 209 pregnant women selected by systematic random sampling from antenatal
      care attendees at primary health care in a rural Local Government Area of Ekiti
      State, Nigeria. Information on knowledge of IPT, delivery, adherence and
      acceptability was obtained using an interviewer administered questionnaire.
      Descriptive statistics such as means, range, proportions were used. Chi-square
      test was used to examine association between categorical variables. All analyses
      were performed at 5% level of significance. RESULTS: One hundred and nine of 209
      (52.2%) respondents have heard about IPTp but only 26 (23.9%) were able to define
      it. Fifty seven (27.3%) reported to have received at least one dose of IPTp
      during the index pregnancy and all were among those who have heard of IPTp
      (52.3%). Twenty one of the 57 (36.8%) took the SP in the clinic. Only three of
      the twenty-one (14.3%) were supervised by a health worker. Twenty two of the 36
      women (61.1%) who did not take their drugs in the clinic would have liked to do
      so if allowed to bring their own drinking cups. Almost half (43.9%) of those who
      had used IPTp during the index pregnancy expressed concern about possible adverse
      effect of SP on their pregnancies. Periodic shortages of SP in the clinics were
      also reported. CONCLUSION: In this study, IPTp use among pregnant women was very
      low and there was poor adherence to the Directly Observed Therapy (DOT) scheme.
      Concerted effort should be made to increase awareness of IPTp among the public
      especially women of child bearing age. Health workers should also be trained and
      monitored to ensure adherence.

PMID- 19589165
TI  - Critical scale of propagation influences dynamics of waves in a model of
      excitable medium.
AB  - BACKGROUND: Duration and speed of propagation of the pulse are essential factors
      for stability of excitation waves. We explore the propagation of excitation waves
      resulting from periodic stimulation of an excitable cable to determine the
      minimal stable pulse duration in a rate-dependent modification of a Chernyak
      Starobin-Cohen reaction-diffusion model. RESULTS: Various pacing rate dependent
      features of wave propagation were studied computationally and analytically. We
      demonstrated that the complexity of responses to stimulation and evolution of
      these responses from stable propagation to propagation block and alternans was
      determined by the proximity between the minimal level of the recovery variable
      and the critical excitation threshold for a stable solitary pulse. CONCLUSION:
      These results suggest that critical propagation of excitation waves determines
      conditions for transition to unstable rhythms in a way similar to unstable
      cardiac rhythms. Established conditions were suitably accurate regardless of rate
      dependent features and the magnitude of the slopes of restitution curves.

PMID- 19589163
TI  - Development of risk maps to minimize uranium exposures in the Navajo Churchrock
      mining district.
AB  - BACKGROUND: Decades of improper disposal of uranium-mining wastes on the Navajo
      Nation has resulted in adverse human and ecological health impacts as well as
      socio-cultural problems. As the Navajo people become increasingly aware of the
      contamination problems, there is a need to develop a risk-communication strategy
      to properly inform tribal members of the extent and severity of the health risks.
      To be most effective, this strategy needs to blend accepted risk-communication
      techniques with Navajo perspectives such that the strategy can be used at the
      community level to inform culturally- and toxicologically-relevant decisions
      about land and water use as well as mine-waste remediation. OBJECTIVE: The
      objective of this study was to develop GIS-based thematic maps as communication
      tools to clearly identify high risk exposure areas and offer alternatives to
      minimize public and ecological health impacts. METHODS: Thematic maps were
      produced that incorporated data derived from environmental sampling and public
      health surveys. The maps show the location and quality of unregulated water
      resources and identify regulated water sources that could be used as
      alternatives. In addition, the maps show the location of contaminated soil and
      sediment areas in which disturbance of surface deposits should be avoided.
      Preliminary feedback was collected from an informal Navajo working group to
      assess the clarity and efficacy of this proposed communication method. RESULTS:
      The working group found the maps to be both clear and effective, and made
      suggestions for improvements, such as the addition of more map features. The
      working group predicted that once the maps are presented to the public, water
      hauling and soil use behaviors will change, and dialogue with chapter officials
      will be initiated to accelerate further risk reduction efforts. IMPLICATIONS:
      Because risk communication is complicated by language barriers, lack of
      infrastructure, and historical mistrust of non-Navajo researchers, mapping
      provides an easily interpretable medium that can be objectively viewed by
      community members and decision makers to evaluate activities that affect toxicant
      exposures.

PMID- 19589166
TI  - The "Excellence in Translational Medicine" and "Bedside-to-Bench" Awards 2007-08.

PMID- 19589168
TI  - A functional difficulty and functional pain instrument for hip and knee
      osteoarthritis.
AB  - INTRODUCTION: The objectives of this study were to develop a functional outcome
      instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item
      response theory (IRT) and computer adaptive test (CAT) methods and to assess its
      psychometric performance compared to the current standard in the field. METHODS:
      We conducted an extensive literature review, focus groups, and cognitive testing
      to guide the construction of an item bank consisting of 125 functional activities
      commonly affected by hip and knee osteoarthritis. We recruited a convenience
      sample of 328 adults with confirmed hip and/or knee osteoarthritis. Subjects
      reported their degree of functional difficulty and functional pain in performing
      each activity in the item bank and completed the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC). Confirmatory factor analyses were
      conducted to assess scale uni-dimensionality, and IRT methods were used to
      calibrate the items and examine the fit of the data. We assessed the performance
      of OA-FUNCTION-CATs of different lengths relative to the full item bank and WOMAC
      using CAT simulation analyses. RESULTS: Confirmatory factor analyses revealed
      distinct functional difficulty and functional pain domains. Descriptive
      statistics for scores from 5-, 10-, and 15-item CATs were similar to those for
      the full item bank. The 10-item OA-FUNCTION-CAT scales demonstrated a high degree
      of accuracy compared with the item bank (r = 0.96 and 0.89, respectively).
      Compared to the WOMAC, both scales covered a broader score range and demonstrated
      a higher degree of precision at the ceiling and reliability across the range of
      scores. CONCLUSIONS: The OA-FUNCTION-CAT provided superior reliability throughout
      the score range and improved breadth and precision at the ceiling compared with
      the WOMAC. Further research is needed to assess whether these improvements carry
      over into superior ability to measure change.

PMID- 19589167
TI  - Molecular fingerprinting of radiation resistant tumors: can we apprehend and
      rehabilitate the suspects?
AB  - Radiation therapy continues to be one of the more popular treatment options for
      localized prostate cancer. One major obstacle to radiation therapy is that there
      is a limit to the amount of radiation that can be safely delivered to the target
      organ. Emerging evidence suggests that therapeutic agents targeting specific
      molecules might be combined with radiation therapy for more effective treatment
      of tumors. Recent studies suggest that modulation of these molecules by a variety
      of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering
      RNA) may enhance the efficacy of radiation therapy by modifying the activity of
      key cell proliferation and survival pathways such as those controlled by Bcl-2,
      p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of
      recent investigations of radiosensitizing agents in the treatment of prostate
      cancer.

PMID- 19589169
TI  - Experimental induction of proventricular dilatation disease in cockatiels
      (Nymphicus hollandicus) inoculated with brain homogenates containing avian
      bornavirus 4.
AB  - BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder of
      psittacine birds worldwide. The disease is characterized by lymphoplasmacytic
      infiltration of the central and peripheral nervous systems, leading to
      gastrointestinal motility and/or central nervous system dysfunction. Recently, we
      detected a significant association between avian bornavirus (ABV) infection and
      clinical signs of PDD in psittacines. However, it remains unclear whether ABV
      infection actually causes PDD. To address this question, we examined the impact
      of ABV inoculation on the cockatiel (Nymphicus hollandicus). RESULTS: Five
      cockatiels were inoculated via multiple routes (intramuscular, intraocular,
      intranasal, and oral) with a brain homogenate derived from either a PDD(+) avian
      bornavirus 4 (ABV4) (+) case (n = 3 inoculees) or from a PDD(-) ABV(-) control (n
      = 2 inoculees). The control birds remained free of clinical or pathological signs
      of PDD, and tested ABV(-) by RT-PCR and immunohistochemistry (IHC). In contrast,
      all three cockatiels inoculated with ABV4(+) brain homogenate developed gross and
      microscopic PDD lesions, and two exhibited overt clinical signs. In numerous
      tissues, ABV RT-PCR and sequence analysis demonstrated the presence of ABV4 RNA
      nearly identical to that in the inoculum. ABV was detected in the central nervous
      system of the three ABV-inoculees by IHC. Pyrosequencing to investigate the viral
      flora in the ABV4(+) inoculum uncovered 7 unique reads sharing 73-100% nucleotide
      sequence identity with previously identified ABV sequences and 24 reads sharing
      40-89% amino acid sequence identity with viruses in the Retroviridae and
      Astroviridae families. Of these candidate viral species, only ABV RNA was
      recovered from tissues of the inoculated birds. CONCLUSION: In this study, the
      clinical and pathological manifestations of PDD were induced by inoculation of
      cockatiels with brain homogenates containing avian bornavirus 4. By using high
      throughput pyrosequencing an in-depth view of the viral content of the inoculum
      was achieved, revealing that of 3 candidate virus families detected, only the
      presence of ABV RNA correlated with the development of PDD. This study provides
      evidence of a causal association between ABV4 infection and PDD in cockatiels.

PMID- 19589170
TI  - Salmonella enterica serovar Typhimurium adhesion and cytotoxicity during
      epithelial cell stress is reduced by Lactobacillus rhamnosus GG.
AB  - BACKGROUND: Physiological stressors may alter susceptibility of the host
      intestinal epithelium to infection by enteric pathogens. In the current study,
      cytotoxic effect, adhesion and invasion of Salmonella enterica serovar
      Typhimurium (S. Typhimurium) to Caco-2 cells exposed to thermal stress (41
      degrees C, 1 h) was investigated. Probiotic bacteria have been shown to reduce
      interaction of pathogens with the epithelium under non-stress conditions and may
      have a significant effect on epithelial viability during infection; however,
      probiotic effect on pathogen interaction with epithelial cells under
      physiological stress is not known. Therefore, we investigated the influence of
      Lactobacillus rhamnosus GG and Lactobacillus gasseri on Salmonella adhesion and
      Salmonella-induced cytotoxicity of Caco-2 cells subjected to thermal stress.
      RESULTS: Thermal stress increased the cytotoxic effect of both S. Typhimurium (P
      = 0.0001) and nonpathogenic E. coli K12 (P = 0.004) to Caco-2 cells, and resulted
      in greater susceptibility of cell monolayers to S. Typhimurium adhesion (P =
      0.001). Thermal stress had no significant impact on inflammatory cytokines
      released by Caco-2 cells, although exposure to S. Typhimurium resulted in greater
      than 80% increase in production of IL-6 and IL-8. Blocking S. Typhimurium with
      anti-ShdA antibody prior to exposure of Salmonella decreased adhesion (P = 0.01)
      to non-stressed and thermal-stressed Caco-2 cells. Pre-exposure of Caco-2 cells
      to L. rhamnosus GG significantly reduced Salmonella-induced cytotoxicity (P =
      0.001) and Salmonella adhesion (P = 0.001) to Caco-2 cells during thermal stress,
      while L. gasseri had no effect. CONCLUSION: Results suggest that thermal stress
      increases susceptibility of intestinal epithelial Caco-2 cells to Salmonella
      adhesion, and increases the cytotoxic effect of Salmonella during infection. Use
      of L. rhamnosus GG as a probiotic may reduce the severity of infection during
      epithelial cell stress. Mechanisms by which thermal stress increases
      susceptibility to S. Typhimurium colonization and by which L. rhamnosus GG limits
      the severity of infection remain to be elucidated.

PMID- 19589171
TI  - Amyloidogenic determinants are usually not buried.
AB  - BACKGROUND: Amyloidoses are a group of usually fatal diseases, probably caused by
      protein misfolding and subsequent aggregation into amyloid fibrillar deposits.
      The mechanisms involved in amyloid fibril formation are largely unknown and are
      the subject of current, intensive research. In an attempt to identify possible
      amyloidogenic regions in proteins for further experimental investigation, we have
      developed and present here a publicly available online tool that utilizes five
      different and independently published methods, to form a consensus prediction of
      amyloidogenic regions in proteins, using only protein primary structure data.
      RESULTS: It appears that the consensus prediction tool is slightly more objective
      than individual prediction methods alone and suggests several previously not
      identified amino acid stretches as potential amyloidogenic determinants, which
      (although several of them may be overpredictions) require further experimental
      studies. The tool is available at: http://biophysics.biol.uoa.gr/AMYLPRED.
      Utilizing molecular graphics programs, like O and PyMOL, as well as the algorithm
      DSSP, it was found that nearly all experimentally verified amyloidogenic
      determinants (short peptide stretches favouring aggregation and subsequent
      amyloid formation), and several predicted, with the aid of the tool AMYLPRED, but
      not experimentally verified amyloidogenic determinants, are located on the
      surface of the relevant amyloidogenic proteins. This finding may be important in
      efforts directed towards inhibiting amyloid fibril formation. CONCLUSION: The
      most significant result of this work is the observation that virtually all, to
      date, experimentally determined amyloidogenic determinants and the majority of
      predicted, but not yet experimentally verified short amyloidogenic stretches, lie
      'exposed' on the surface of the relevant amyloidogenic proteins, and also several
      of them have the ability to act as conformational 'switches'. Experiments,
      focused on these fragments, should be performed to test this idea.

PMID- 19589172
TI  - Record linkage to obtain birth outcomes for the evaluation of screening
      biomarkers in pregnancy: a feasibility study.
AB  - BACKGROUND: Linking population health data to pathology data is a new approach
      for the evaluation of predictive tests that is potentially more efficient,
      feasible and efficacious than current methods. Studies evaluating the use of
      first trimester maternal serum levels as predictors of complications in pregnancy
      have mostly relied on resource intensive methods such as prospective data
      collection or retrospective chart review. The aim of this pilot study is to
      demonstrate that record-linkage between a pathology database and routinely
      collected population health data sets provides follow-up on patient outcomes that
      is as effective as more traditional and resource-intensive methods. As a specific
      example, we evaluate maternal serum levels of PAPP-A and free beta-hCG as
      predictors of adverse pregnancy outcomes, and compare our results with those of
      prospective studies. METHODS: Maternal serum levels of PAPP-A and free beta-hCG
      for 1882 women randomly selected from a pathology database in New South Wales
      (NSW) were linked to routinely collected birth and hospital databases. Crude
      relative risks were calculated to investigate the association between low levels
      (multiples of the median < or = 5th percentile) of PAPP-A or free beta-hCG and
      the outcomes of preterm delivery (<37 weeks), small for gestational age (<10th
      percentile), fetal loss and stillbirth. RESULTS: Using only full name, sex and
      date of birth for record linkage, pregnancy outcomes were available for 1681
      (89.3%) of women included in the study. Low levels of PAPP-A had a stronger
      association with adverse pregnancy outcomes than a low level of free beta-hCG
      which is consistent with results in published studies. The relative risk of
      having a preterm birth with a low maternal serum PAPP-A level was 3.44 (95% CI
      1.96-6.10) and a low free beta-hCG level was 1.31 (95% CI 0.55-6.16). CONCLUSION:
      This study provides data to support the use of record linkage for outcome
      ascertainment in studies evaluating predictive tests. Linkage proportions are
      likely to increase if more personal identifiers are available. This method of
      follow-up is a cost-efficient technique and can now be applied to a larger cohort
      of women.

PMID- 19589173
TI  - Rationales, design and recruitment of the Taizhou Longitudinal Study.
AB  - BACKGROUND: Rapid economic growth in China in the past decades has been
      accompanied by dramatic changes in lifestyle and environmental exposures. The
      burdens of non-communicable diseases, such as cardiovascular diseases, diabetes
      and cancer, have also increased substantially. METHODS/DESIGN: We initiated a
      large prospective cohort-the Taizhou Longitudinal Study-in Taizhou (a medium-size
      city in China) to explore the environmental and genetic risk factors for common
      non-communicable diseases. The sample size of the cohort will be at least 100,000
      adults aged 30-80 years drawn from the general residents of the districts of
      Hailin, Gaogang, and Taixing (sample frame, 1.8 million) of Taizhou. A three
      stage stratified sampling method will be applied. Baseline investigations include
      interviewer-administered questionnaire, anthropometric measurements, and
      collection of buccal mucosal cells and blood specimens. DNA will be extracted for
      genetic studies and serum samples will be used for biochemical examinations. A
      follow-up survey will be conducted every three years to obtain information on
      disease occurrence and information on selected lifestyle exposures. Study
      participants will be followed-up indefinitely by using a chronic disease register
      system for morbidity and cause-specific mortality. Information on non-fatal
      events will be obtained for certain major categories of disease (e.g., cancer,
      stroke, myocardial infarction) through established registry systems. DISCUSSION:
      The Taizhou Longitudinal Study will provide a good basis for exploring the roles
      of many important environmental factors (especially those concomitant with the
      economic transformation in China) for common chronic diseases, solely or via
      interaction with genetic factors.

PMID- 19589174
TI  - Alternative use of multiple exons 1 of aromatase gene in cancerous and normal
      breast tissues from women over the age of 80 years.
AB  - INTRODUCTION: Peripherally localized aromatase, which converts circulating
      androgens into estrogens, is important in the pathogenesis of postmenopausal
      breast carcinomas. We have previously shown that aromatase mRNA levels are higher
      in elderly breast carcinomas (EldCa) than breast carcinomas of the control group
      (ContCa) or normal breast tissues. Aromatase expression has been reported to be
      regulated through the alternative use of multiple exons 1 (exons 1a-1f and so
      on); however, the preferential usage of exons 1 in elderly breast tissue has
      never been systematically examined. In order to properly treat and protect
      against EldCa, the regulation mechanism of aromatase expression in elderly breast
      tissues should be elucidated. The aim of the present study is to elucidate
      whether there are any specific patterns in use of multiple exons 1 in elderly
      breast tissue. METHODS: Usage of multiple exons 1 of the aromatase gene and mRNA
      levels of aromatase were examined by reverse transcription-polymerase chain
      reaction analysis in breast tissues of 38 elderly patients with breast cancer
      (age 80-99), and the results were compared with those in 35 patients of the
      control group (age 37-70). One-factor analysis of variance and the Scheffe test
      were used for the comparison of aromatase mRNA levels. Patterns of preferential
      utilization of multiple exons 1 of the aromatase gene were compared by chi2 test
      for independence or Fisher exact test for independence using a contingency table.
      RESULTS: Exon 1d was utilized much more frequently in elderly tissue than in the
      control group irrespective of cancerous or normal tissue (EldCa, 36/38, 95%
      versus ContCa, 7/35, 20%, P < 0.0001; normal tissue of the elderly, EldNorm,
      30/34, 88% versus normal tissue of controls, ContNorm, 2/29, 7%, P < 0.0001).
      Twenty EldCa (53%) and 12 EldNorm (35%) used both exons 1c and 1d; however, their
      dominance was reversed (EldCa, all 1d > 1c; EldNorm, all 1c > 1d). CONCLUSIONS:
      Elderly breast tissues exhibited specific patterns in use of multiple exons 1,
      which at least partly explained the higher aromatase levels in EldCa. The
      mechanisms of how these specific patterns occur during aging and carcinogenesis
      should be further examined.

PMID- 19589176
TI  - Health literacy: setting an international collaborative research agenda.
AB  - BACKGROUND: Health literacy is an increasingly important topic in both the policy
      and research agendas of many countries. During the recent 36th Annual Meeting of
      the North American Primary Care Research Group, the authors led an audio-taped 3
      hour forum, "Studying Health Literacy: Developing an International
      Collaboration," where the current state of health literacy (HL) in the United
      States (US) and United Kingdom (UK) was presented and attendees were encouraged
      to debate a future research agenda. DISCUSSION OF FORUM THEMES: The debate
      centred around three distinct themes, including: (1) refining HL definitions and
      conceptual models, (2) HL measurement and assessment tools, and (3) developing a
      collaborative international research agenda. The attendees agreed that future
      research should be theoretically grounded and conceptual models employed in
      studies should be explicit to allow for international comparisons to be drawn.
      SUMMARY AND AUTHORS REFLECTIONS: The importance of HL research and its possible
      contribution to health disparities is becoming increasingly recognised
      internationally. International collaborations and comparative studies could
      illuminate some of the possible determinants of disparities, and also possibly
      provide a vehicle to examine other research questions of interest.

PMID- 19589175
TI  - Understanding the Relationship between Activity and Neighbourhoods (URBAN) Study:
      research design and methodology.
AB  - BACKGROUND: Built environment attributes are recognized as being important
      contributors to physical activity (PA) engagement and body size in adults and
      children. However, much of the existing research in this emergent public health
      field is hindered by methodological limitations, including: population and site
      homogeneity, reliance on self-report measures, aggregated measures of PA, and
      inadequate statistical modeling. As an integral component of multi-country
      collaborative research, the Understanding the Relationship between Activity and
      Neighbourhoods (URBAN) Study seeks to overcome these limitations by determining
      the strengths of association between detailed measures of the neighborhood built
      environment with PA levels across multiple domains and body size measures in
      adults and children. This article outlines the research protocol developed for
      the URBAN Study. METHODS AND DESIGN: The URBAN Study is a multi-centered,
      stratified, cross-sectional research design, collecting data across four New
      Zealand cities. Within each city, 12 neighborhoods were identified and selected
      for investigation based on higher or lower walkability and Maori demographic
      attributes. Neighborhoods were selected to ensure equal representation of these
      characteristics. Within each selected neighborhood, 42 households are being
      randomly selected and an adult and child (where possible) recruited into the
      study. Data collection includes: objective and self-reported PA engagement,
      neighborhood perceptions, demographics, and body size measures. The study was
      designed to recruit approximately 2,000 adults and 250 children into the project.
      Other aspects of the study include photovoice, which is a qualitative assessment
      of built environment features associated with PA engagement, an audit of the
      neighborhood streetscape environment, and an individualized neighborhood
      walkability profile centered on each participant's residential address.
      Multilevel modeling will be used to examine the individual-level and neighborhood
      level relationships with PA engagement and body size. DISCUSSION: The URBAN Study
      is applying a novel scientifically robust research design to provide urgently
      needed epidemiological information regarding the associations between the built
      environment and health outcomes. The findings will contribute to a larger,
      international initiative in which similar neighborhood selection and PA
      measurement procedures are utilized across eight countries. Accordingly, this
      study directly addresses the international priority issues of increasing PA
      engagement and decreasing obesity levels.

PMID- 19589177
TI  - Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome
      in the Vietnamese population.
AB  - BACKGROUND: In Vietnam the blackwater fever syndrome (BWF) has been associated
      with malaria infection, quinine ingestion and G6PD deficiency. The G6PD variants
      within the Vietnamese Kinh contributing to the disease risk in this population,
      and more generally to haemoglobinuria, are currently unknown. METHOD: Eighty-two
      haemoglobinuria patients and 524 healthy controls were screened for G6PD
      deficiency using either the methylene blue reduction test, the G-6-PDH kit or the
      micro-methaemoglobin reduction test. The G6PD gene variants were screened using
      SSCP combined with DNA sequencing in 82 patients with haemoglobinuria, and in 59
      healthy controls found to be G6PD deficient. RESULTS: This study confirmed that
      G6PD deficiency is strongly associated with haemoglobinuria (OR = 15, 95% CI [7.7
      to 28.9], P < 0.0001). Six G6PD variants were identified in the Vietnamese
      population, of which two are novel (Vietnam1 [Glu3Lys] and Vietnam2 [Phe66Cys]).
      G6PD Viangchan [Val291Met], common throughout south-east Asia, accounted for 77%
      of the variants detected and was significantly associated with haemoglobinuria
      within G6PD-deficient ethnic Kinh Vietnamese (OR = 5.8 95% CI [114-55.4], P =
      0.022). CONCLUSION: The primary frequency of several G6PD mutations, including
      novel mutations, in the Vietnamese Kinh population are reported and the
      contribution of G6PD mutations to the development of haemoglobinuria are
      investigated.

PMID- 19589180
TI  - Immunonutrition in critical illness: still fishing for the truth.

PMID- 19589178
TI  - Paraphyly of organelle DNAs in Cycas Sect. Asiorientales due to ancient ancestral
      polymorphisms.
AB  - BACKGROUND: This study addresses the apportionment of genetic diversity between
      Cycas revoluta and C. taitungensis, species that constitute the section
      Asiorientales and represent a unique, basal lineage of the Laurasian genus Cycas.
      Fossil evidence indicates divergence of the section from the rest of Cycas at
      least 30 million years ago. Geographically, C. taitungensis is limited to Taiwan
      whereas C. revoluta is found in the Ryukyu Archipelago and on mainland China.
      RESULTS: The phylogenies of ribosomal ITS region of mtDNA and the intergenic
      spacer between atpB and rbcL genes of cpDNA were reconstructed. Phylogenetic
      analyses revealed paraphyly of both loci in the two species and also in the
      section Asiorientales. The lack of reciprocal monophyly between these long
      isolated sections is likely due to persistent shared ancestral polymorphisms.
      Molecular dating estimated that mt- and cp DNA lineages coalesced to the most
      recent common ancestors (TMRCA) about 327 (mt) and 204 MYA (cp), corresponding
      with the divergence of cycad sections in the Mesozoic. CONCLUSION: Fates of newly
      derived mutations of cycads follow Klopfstein et al.'s surfing model where the
      majority of new mutations do not spread geographically and remain at low
      frequencies or are eventually lost by genetic drift. Only successful 'surfing
      mutations' reach very high frequencies and occupy a large portion of a species
      range. These mutations exist as dominant cytotypes across populations and
      species. Geographical subdivision is lacking in both species, even though
      recurrent gene flow by both pollen and seed is severely limited. In total, the
      contrasting levels between historical and ongoing gene flow, large population
      sizes, a long lifespan, and slow mutation rates in both organelle DNAs have all
      likely contributed to the unusually long duration of paraphyly in cycads.

PMID- 19589179
TI  - Expression of the peroxisome proliferator activated receptor gamma gene is
      repressed by DNA methylation in visceral adipose tissue of mouse models of
      diabetes.
AB  - BACKGROUND: Adipose tissues serve not only as a store for energy in the form of
      lipid, but also as endocrine tissues that regulates metabolic activities of the
      organism by secreting various kinds of hormones. Peroxisome proliferator
      activated receptor gamma (PPARgamma) is a key regulator of adipocyte
      differentiation that induces the expression of adipocyte-specific genes in
      preadipocytes and mediates their differentiation into adipocytes. Furthermore,
      PPARgamma has an important role to maintain the physiological function of mature
      adipocyte by controlling expressions of various genes properly. Therefore, any
      reduction in amount and activity of PPARgamma is linked to the pathogenesis of
      metabolic syndrome. RESULTS: In this study, we investigated the contribution of
      epigenetic transcriptional regulatory mechanisms, such as DNA methylation, to the
      expression of the PPARgamma gene, and further evaluated the contribution of such
      epigenetic regulatory mechanisms to the pathogenesis of metabolic syndrome. In
      3T3-L1 preadipocytes, the promoter of the PPARgamma2 gene was hypermethylated,
      but was progressively demethylated upon induction of differentiation, which was
      accompanied by an increase of mRNA expression. Moreover, treatment of cells with
      5'-aza-cytideine, an inhibitor of DNA methylation, increased expression of the
      PPARgamma gene in a dose-dependent manner. Methylation in vitro of a PPARgamma
      promoter-driven reporter construct also repressed the transcription of a
      downstream reporter gene. These results suggest that the expression of the
      PPARgamma gene is inhibited by methylation of its promoter. We next compared the
      methylation status of the PPARgamma promoters in adipocytes from wild-type (WT)
      mice with those from two diabetic mouse models: +Leprdb/+Leprdb and diet-induced
      obesity mice. Interestingly, we found increased methylation of the PPARgamma
      promoter in visceral adipose tissues (VAT) of the mouse models of diabetes,
      compared to that observed in wild-type mice. We observed a concomitant decrease
      in the level of PPARgamma mRNA in the diabetic mice compared to the WT mice.
      CONCLUSION: We conclude that the expression of PPARgamma gene is regulated by DNA
      methylation of its promoter region and propose that reduced expression of
      PPARgamma owing to DNA methylation in adipocytes of the VAT may contribute to the
      pathogenesis of metabolic syndrome.

PMID- 19589181
TI  - Transposons that clean up after themselves.
AB  - A transposon in the germline genome of the ciliate Oxytricha uses its transposase
      to remove itself, as well as other germline-limited DNA, from the differentiating
      somatic genome during development.

PMID- 19589184
TI  - Q&A: Cooperativity.

PMID- 19589182
TI  - The WASP and WAVE family proteins.
AB  - All eukaryotic cells need to reorganize their actin cytoskeleton to change shape,
      divide, move, and take up nutrients for survival. The Wiskott-Aldrich syndrome
      protein (WASP) and WASP-family verprolin-homologous protein (WAVE) family
      proteins are fundamental actin-cytoskeleton reorganizers found throughout the
      eukaryotes. The conserved function across species is to receive upstream signals
      from Rho-family small GTPases and send them to activate the Arp2/3 complex,
      leading to rapid actin polymerization, which is critical for cellular processes
      such as endocytosis and cell motility. Molecular and cell biological studies have
      identified a wide array of regulatory molecules that bind to the WASP and WAVE
      proteins and give them diversified roles in distinct cellular locations. Genetic
      studies using model organisms have also improved our understanding of how the
      WASP- and WAVE-family proteins act to shape complex tissue architectures. Current
      efforts are focusing on integrating these pieces of molecular information to draw
      a unified picture of how the actin cytoskeleton in a single cell works
      dynamically to build multicellular organization.

PMID- 19589183
TI  - Oxidative stress, thermogenesis and evolution of uncoupling proteins.
AB  - The uncoupling protein UCP1 provides eutherian mammals with an efficient
      thermogenic mechanism. Recent work published in BMC Evolutionary Biology,
      following the identification of UCP1 orthologs in non-eutherians, concludes that
      this unique function appeared after sequence divergence and purifying selection
      that allowed functional co-option.

PMID- 19589185
TI  - Mapping multiple quantitative trait loci under Bayes error control.
AB  - In mapping of quantitative trait loci (QTLs), performing hypothesis tests of
      linkage to a phenotype of interest across an entire genome involves multiple
      comparisons. Furthermore, linkage among loci induces correlation among tests.
      Under many multiple comparison frameworks, these problems are exacerbated when
      mapping multiple QTLs. Traditionally, significance thresholds have been
      subjectively set to control the probability of detecting at least one false
      positive outcome, although such thresholds are known to result in excessively low
      power to detect true positive outcomes. Recently, false discovery rate (FDR)
      controlling procedures have been developed that yield more power both by relaxing
      the stringency of the significance threshold and by retaining more power for a
      given significance threshold. However, these procedures have been shown to
      perform poorly for mapping QTLs, principally because they ignore recombination
      fractions between markers. Here, I describe a procedure that accounts for
      recombination fractions and extends FDR control to include simultaneous control
      of the false non-discovery rate, i.e. the overall error rate is controlled. This
      procedure is developed in the Bayesian framework using a direct posterior
      probability approach. Data-driven significance thresholds are determined by
      minimizing the expected loss. The procedure is equivalent to jointly maximizing
      positive and negative predictive values. In the context of mapping QTLs for
      experimental crosses, the procedure is applicable to mapping main effects, gene
      gene interactions and gene-environment interactions.

PMID- 19589186
TI  - Resistance to Salmonella carrier state: selection may be efficient but response
      depends on animal's age.
AB  - Increasing resistance to acute salmonellosis (defined as bacteraemia in animals
      showing symptoms) is not sufficient for food safety, because of the risk of
      carrier state (when animals excrete bacteria without showing any symptoms).
      Increased resistance to Salmonella carrier state is therefore needed. Two
      experiments of divergent selection on resistance at a younger and a later age
      lead to significant differences between lines and allowed estimating genetic
      parameters on 4262 animals. Heritability of resistance was estimated at 0.16 in
      chicks, while it varied from 0.14 to 0.23 with analysed organ in adult hens.
      Genetic correlations between contamination of the different organs ranged from
      0.46 to 0.67, while correlations between resistance at both ages were estimated
      at -0.50, showing that increasing genetic resistance of hens will reduce
      resistance in chicks. Highest estimated absolute values of genetic correlations
      between resistance and production traits were, for chicken contamination level,
      with number of eggs laid between 41 and 60 (0.37) and, for adult contamination,
      with number of eggs laid between 18 and 24 (0.37) or 25 and 40 (-0.33) weeks of
      age.

PMID- 19589187
TI  - Molecular signature of epistatic selection: interrogating genetic interactions in
      the sex-ratio meiotic drive of Drosophila simulans.
AB  - Fine scale analyses of signatures of selection allow assessing quantitative
      aspects of a species' evolutionary genetic history, such as the strength of
      selection on genes. When several selected loci lie in the same genomic region,
      their epistatic interactions may also be investigated. Here, we study how the
      neutral polymorphism pattern was shaped by two close recombining loci that cause
      'sex-ratio' meiotic drive in Drosophila simulans, as an example of strong
      selection with potentially strong epistasis. We compare the polymorphism data
      observed in a natural population with the results of forward stochastic
      simulations under several contexts of epistasis between the candidate loci for
      the drive. We compute the likelihood of different possible scenarios, in order to
      determine which configuration is most consistent with the data. Our results
      highlight that fine scale analyses of well-chosen candidate genomic regions
      provide information-rich data that can be used to investigate the genotype
      phenotype-fitness map, which can hardly be studied in genome-wide analyses. We
      also emphasize that initial conditions and time of observation (here, time after
      the interruption of a partial selective sweep) are crucial parameters in the
      interpretation of real data, while these are often overlooked in theoretical
      studies.

PMID- 19589188
TI  - Correlation measures for linkage disequilibrium within and between populations.
AB  - Correlation statistics can be used to measure the amount of linkage
      disequilibrium (LD) between two loci in subdivided populations. Within
      populations, the square of the correlation of gene frequencies, r2, is a
      convenient measure of LD. Between populations, the statistic rirj, for
      populations i and j, measures the relatedness of LD. Recurrence relationships for
      these two parameters are derived for the island model of population subdivision,
      under the assumptions of the linked identity-by-descent (LIBD) model in which
      correlation measures are equated to probability measures. The recurrence
      relationships closely predict the build-up of r2 and rirj following population
      subdivision in computer simulations. The LIBD model predicts that a steady state
      will be reached with r2 equal to 1/[1+4Nec(1+(k-1)rho)], where k is the number of
      island populations, Ne is the effective local population (island) size, and rho
      measures the ratio of migration (m) to recombination (c) and is equal to m/[c(k
      1)+m]. For low values of m/c, rho=0, and E(r2) is equal to 1/(1+4Nec). For high
      values of m/c, rho=1, and E(r2) is equal to 1/(1+4kNec). The value of rirj
      following separation eventually settles down to a steady state whose expectation,
      E(rirj), is equal to E(r2) multiplied by rho. Equations predicting the change in
      rirj values are applied to the separation of African (Yoruba - YRI) and non
      African (European - CEU) populations, using data from Hapmap. The primary data
      lead to an estimate of separation time of less than 1000 generations if there has
      been no migration, which is around one-third of minimum current estimates.
      Ancient rather than recent migration can explain the form of the data.

PMID- 19589189
TI  - Bayesian prediction of breeding values by accounting for genotype-by-environment
      interaction in self-pollinating crops.
AB  - In self-pollinating populations, individuals are characterized by a high degree
      of inbreeding. Additionally, phenotypic observations are highly influenced by
      genotype-by-environment interaction effects. Usually, Bayesian approaches to
      predict breeding values (in self-pollinating crops) omit genotype-by-environment
      interactions in the statistical model, which may result in biased estimates. In
      our study, a Bayesian Gibbs sampling algorithm was developed that is adapted to
      the high degree of inbreeding in self-pollinated crops and accounts for
      interaction effects between genotype and environment. As related lines are
      supposed to show similar genotype-by-environment interaction effects, an extended
      genetic relationship matrix is included in the Bayesian model. Additionally,
      since the coefficient matrix C in the mixed model equations can be characterized
      by rank deficiencies, the pseudoinverse of C was calculated by using the
      nullspace, which resulted in a faster computation time. In this study, field data
      of spring barley lines and data of a 'virtual' parental population of self
      pollinating crops, generated by computer simulation, were used. For comparison,
      additional breeding values were predicted by a frequentist approach. In general,
      standard Bayesian Gibbs sampling and a frequentist approach resulted in similar
      estimates if heritability of the regarded trait was high. For low heritable
      traits, the modified Bayesian model, accounting for relatedness between lines in
      genotype-by-environment interaction, was superior to the standard model.

PMID- 19589190
TI  - Pedigree analysis for conservation of genetic diversity and purging.
AB  - We present an approach to describe and evaluate changes in genetic diversity and
      to calculate bounds for improvement. This pedigree-based analysis was applied to
      the Kromfohrlander dog (FCI Gr9 Sec10). Pedigrees trace back to the foundation of
      the breed and were available for 5527 individuals. Based on this dataset the
      population structure and historical bottlenecks were studied. Distributions of
      allele frequencies were estimated by Monte Carlo simulation. To monitor changes
      in mating systems throughout the breeding history, the homozygosity of alleles
      was compared with their expectations in Hardy-Weinberg equilibrium. Different
      breeding lines were identified by hierarchical cluster analysis and were
      characterized by ancestor contributions. Our calculations showed that the founder
      event in 1945 was followed by two bottlenecks. One was caused by strong selection
      in a very small population, and the other was triggered by rigorous disease
      management. The necessary amount of purging that arised due to the bottlenecks
      was also discussed.

PMID- 19589191
TI  - The Environmental Cleanliness and Clutter Scale (ECCS).
AB  - BACKGROUND: Development of a scale to rate the degree and various aspects of
      uncleanliness will facilitate description and research in cases of severe
      domestic squalor. METHODS: Discussion with representatives of relevant agencies
      led to selection of various aspects of domestic uncleanliness and clutter to be
      assessed when describing cases of squalor. Rooms and areas with varying functions
      (toilet, kitchen, bedroom, etc.) were all to be rated, along with other
      indicators of squalor (e.g. odor, vermin). Trial use and further discussion
      resulted in reduction to ten items, each rated on a four-point scale, with
      succinct descriptions of anchor-points. Two experienced psychogeriatricians then
      used this new Environmental Cleanliness and Clutter Scale (ECCS) to rate
      independently 55 dwellings which had been reported by Aged Care staff as
      cluttered or unclean, and also rated overall degree of squalor. Reliability and
      indications of validity were analyzed. RESULTS: The inter-rater reliability for
      the ten items was considered satisfactory (kappa 0.48, varying from 0.31 to
      0.58). Cronbach's alpha for the new scale was 0.94, demonstrating high internal
      consistency. Each author's ratings of degree of squalor (none to severe) matched
      well with the other's ratings on the scale; a score of >12 usually indicated
      moderate or severe squalor. CONCLUSION: The ECCS proved reliable and useful in
      rating cases where elderly people were living in severe domestic squalor.

PMID- 19589192
TI  - Gender differences in predictors of nursing home placement in the elderly: a
      systematic review.
AB  - BACKGROUND: In recent decades a substantial number of studies have examined
      predictors of nursing home placement (NHP) in the elderly. This study provides a
      systematic review of gender-differences in predictors of NHP from population
      based, longitudinal studies worldwide. METHODS: Relevant articles were identified
      by a systematic search of literature. The articles based on prospective studies
      with representative samples of community-living elders identified predictors by
      gender-specific multivariate analyses. RESULTS: Eleven studies were identified.
      We found gender differences in the prediction of NHP for marital status, living
      situation, housing and car availability and urinary incontinence. For both
      genders the risk of NHP did not differ substantially for age, functional
      impairment, cognitive impairment, dementia, and depression. The male to female
      ratio of admission rates ranged between 1 to 1.4 and 1 to 1.6. CONCLUSIONS: Only
      a few studies analyzed gender-specific predictors of NHP, probably owing to the
      associated statistical difficulties. However, gender differences in prediction of
      NHP do actually exist, and this should encourage further research activities in
      this area using appropriate statistical methods.

PMID- 19589193
TI  - National alcohol consumption and suicide rates.

PMID- 19589194
TI  - How and when to intervene in cases of severe domestic squalor.
AB  - BACKGROUND: Little has been published concerning how best to intervene in cases
      of severe domestic squalor. METHODS: Background literature and reports on how
      best to intervene in cases of severe domestic squalor were reviewed. RESULTS:
      Reports by groups in London (Ontario), and Sydney (Australia) have provided
      recommendations for development of coordinated services to intervene in cases of
      squalor. Guidelines have been issued. Treatments for compulsive hoarding may
      contribute to improvement in cases where squalor is attributable to restricted
      access due to clutter. CONCLUSIONS: Effective interventions in cases of severe
      domestic squalor are commonly expensive and require good inter-agency
      collaboration. Budgetary support must be available to enable appropriate services
      to take on cases and provide case management.

PMID- 19589195
TI  - Top cited papers in international psychogeriatrics: 5. A controlled study of
      repetitive transcranial magnetic stimulation as a treatment of depression in the
      elderly.

PMID- 19589196
TI  - A replication of a cross-national study of the relationship between elderly
      suicide rates and urbanization.

PMID- 19589197
TI  - Tenascin-C is induced in cerebral vasospasm after subarachnoid hemorrhage in rats
      and humans: a pilot study.
AB  - OBJECTIVE: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) has
      been hypothesized to occur because of both inflammation-mediated sustained
      contraction of smooth muscle cells and vascular remodeling. As our recent study
      showed that tenascin-C (TN-C), an extracellular matrix glycoprotein which is up
      regulated in inflammatory states and is associated with tissue remodeling, causes
      vasospasm-like changes in arterial walls, we examined whether TN-C might be
      induced in relation to the occurrence of cerebral vasospasm experimentally and
      clinically. METHODS: First, rat models were produced by means of a single
      cisternal injection of either autologous arterial blood or saline. Immunostaining
      for TN-C was performed with basilar arteries obtained from non-operated rats
      (n=3) and on days 1-4 in SAH (n=18) or saline-injected (n=12) rats. Second,
      levels of TN-C were prospectively measured in serum in 31 consecutive patients
      diagnosed with aneurysmal SAH on days 1-12 and compared between those with and
      without subsequent cerebral vasospasm. RESULTS: In SAH rats, marked induction of
      TN-C immunoreactivity was shown throughout the vasospastic arterial wall,
      especially in the smooth muscle cell layers, in comparison with control rats. In
      a clinical study, serum TN-C levels increased transiently, the extent being
      significantly greater in patients with subsequent vasospasm; the peak occurred
      2.4 days before an increase in the mean transcranial Doppler velocity to > or
      =120 cm/s and 3.6 days before the onset of symptomatic vasospasm (n=14).
      DISCUSSION: This is the first study suggesting TN-C increases with close linkage
      to the occurrence of vasospasm after SAH.

PMID- 19589198
TI  - New laboratory markers in diagnosis of alzheimer dementia.
AB  - OBJECTIVES: The aim of our work was to assess the role of tau protein, beta
      amyloid and cystatin C in diagnosis of Alzheimer dementia (AD) and other
      neurodegenerative diseases (NDs). METHODS: The levels of tau protein, beta
      amyloid and cystatin C were assessed in a set of 79 patients with ND (38 men and
      41 women; aged 22-90 years; mean, 61.6 +/- 15.6 years) and in a control group of
      79 subjects with a healthy central nervous system (38 men and 41 women; aged 20
      91 years; mean, 61.5 +/- 15.1 years). RESULTS: When compared with the subjects in
      the control group, a statistically significant decrease in tau protein levels was
      found in patients with ND, an increase in tau protein levels in patients with AD
      and an increase in cystatin C cerebrospinal fluid/serum index in the ND + AD
      group. DISCUSSION: Our work only confirmed the previously reported results in
      part. Although tau protein seems to be a quite reliable marker of AD, the role of
      beta amyloid in AD diagnosis remains at the least questionable. In the case of
      cystatin C, our results would seem to confirm the views of certain authors that
      cystatin C will probably not become a new 'revolutionary' marker contributing to
      differential diagnostics.

PMID- 19589200
TI  - P300 as an index of implicit self-esteem.
AB  - OBJECTIVE: To explore the neural substrates of implicit self-esteem in university
      students. METHODS: The subjects comprised four females and six males (aged 20-25
      years). They were asked to finish the implicit association test (IAT) for
      implicit self-esteem while brain electrical activity was recorded at 64 scalp
      sites using tin electrodes mounted in an elastic cap. Mean amplitudes were
      analysed using a three-way repeated-measure analyses of variance (ANOVA). The
      ANOVA factors were anterior-posterior electrode location (F, FC, C, CP, P), left
      right electrode location (left, middle, right) and task type (self items in the
      congruent and the incongruent conditions). RESULTS: Robust behavioral data
      indicated that the participants responded relatively rapidly in the congruent
      condition when associating self with positive items, supporting the hypothesis
      that most people have a positive attitude towards self. Scalp event-related brain
      potential analysis revealed that self items in the congruent condition elicited a
      more positive ERP deflection than those in the incongruent condition between 350
      and 450 ms after the onset of the self items (P300). DISCUSSION: P300 has been
      shown to be an index of attention to self-relevant stimuli.

PMID- 19589199
TI  - Reduced Nrf2 and Phase II enzymes expression in immune-mediated spinal cord motor
      neuron injury.
AB  - The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2),
      a major regulator of genes encoding Phase II detoxifying enzymes and antioxidant
      proteins, is important for protecting cells against oxidative damage. In this
      work, we report that in the immune-mediated motor neuron injury animal model,
      expression of Nrf2 and antioxidative enzymes including glutathione S-transferase,
      nicotinamide adenine dinucleotide phosphate (reduced)-quinone oxidoreductase 1
      and heme oxygenase 1 were greatly reduced in motor neurons of spinal cord
      anterior horn in paralyzed guinea pigs, whereas the antioxidant enzymes in the
      dorsal horn of paralyzed guinea pigs were generally preserved. Our findings
      suggest that declined antioxidative capacity may contribute to the damage to
      motor neurons in the process of immune-mediated motor neuron injury. Although the
      exact mechanism of immune reactivity and Nrf2-antioxidant response element
      pathway inactivation remains to be elucidated, inducers of Phase II
      detoxification enzymes may be an attractive therapeutic target for immune
      mediated motor neuron degeneration.

PMID- 19589201
TI  - Persistent outpatient hyperglycemia is independently associated with survival,
      recurrence and malignant degeneration following surgery for hemispheric low grade
      gliomas.
AB  - OBJECTIVE: Hyperglycemia has been shown to augment tumor growth in vitro.
      However, the effects of persistent hyperglycemia on survival, recurrence and
      malignant degeneration in patients undergoing surgery for low grade gliomas
      remain unknown. METHODS: All patients who underwent a craniotomy for hemispheric
      low grade glioma (WHO grade II) from 1996 to 2006 at a single institution were
      retrospectively reviewed. Persistent hyperglycemia was defined as serum glucose
      >180 microg/dl occurring three or more times between 1 and 3 months post
      operatively. The independent association of outpatient glucose levels and
      recorded clinical and treatment variables with overall survival, tumor recurrence
      and malignant degeneration was assessed via separate multivariate proportional
      hazards regression analyses. RESULTS: In this study, 182 patients (89 fibrillary
      astrocytomas, 82 oligodendrogliomas and 11 mixed gliomas) were available for
      analysis. Eighteen (10%) patients experienced persistent hyperglycemia. Patients
      experiencing persistent hyperglycemia were older (44 +/- 16 versus 34 +/- 15) and
      more frequently diabetic [3 (17%) versus 4 (2%)]. All other clinical and
      treatment variables were not significantly different between the two cohorts.
      After adjusting for inter-group differences including age and diabetes and
      variables associated with survival and recurrence, persistent hyperglycemia was
      independently associated with decreased survival (p=0.001), increased recurrence
      (p=0.0001) and increased malignant degeneration (p<0.0001). This remained true
      after excluding all patients with diabetes and those on continued steroid
      administration. Five-year overall survival, progression-free survival and
      malignancy-free survival for persistent hyperglycemia versus relatively
      euglycemic cohorts were 43% versus 84%, 16% versus 46% and 46% versus 77%,
      respectively. DISCUSSION: These findings may provide useful insight for
      increasing survival, decreasing tumor recurrence and decreasing malignant
      degeneration in patients undergoing surgery for low grade gliomas.

PMID- 19589202
TI  - Clinical and functional outcomes of laminoplasty and laminectomy.
AB  - OBJECTIVE: Laminoplasty has become a common alternative to laminectomy for
      cervical spondylotic myelopathy or radiculopathy. The procedures have been
      compared before, but data on functional recovery are limited. We aim to compare
      the safety and short-term clinical and functional outcomes of cervical
      laminoplasty and cervical laminectomy. METHODS: We performed a retrospective
      analysis of the outcome of 72 patients who had laminoplasty and 49 patients who
      had laminectomy at our hospital from 1999 to 2005. Patients had cervical
      spondylotic myelopathy or radiculopathy. All of the patients were similar in age
      and pre-operative functional status. All patients were assessed pre-operatively
      and 4 months post-operatively with the Rankin disability score, Glasgow outcome
      scale and Karnofsky and Nurick scales. RESULTS: Laminoplasty resulted in greater
      improvement than laminectomy on the Rankin scale (p<0.0001, chi-square test), GOS
      (p<0.0027, chi-square test) and Karnofsky scores (p<0.01, Wilcoxon test). Nurick
      scores improved in both groups without a significant difference (p<0.62, Wilcoxon
      test). The proportion of patients who improved on all scales tended to be greater
      in the laminoplasty group. Patients spent 1.8 fewer days in the hospital after
      laminoplasty (p=0.04, Wilcoxon rank-sum test). There was no mortality or
      permanent morbidity for either procedure. CONCLUSION: Both cervical laminectomy
      and laminoplasty are safe and effective for the treatment of cervical myelopathy
      or radiculopathy. Cervical laminoplasty results in a shorter hospital stay and
      greater functional improvement at 4 months follow-up.

PMID- 19589203
TI  - Adenovirus mediated transfer of p53, GM-CSF and B7-1 suppresses growth and
      enhances immunogenicity of glioma cells.
AB  - OBJECTIVES: Malignant gliomas are good targets for gene therapy because they have
      been proven incurable with conventional treatments. However, malignant gliomas
      are genetically and physiologically highly heterogeneous, and current gene
      therapy interventions have been designed to target only a few variations of this
      kind of disease. Hence, we developed a combined gene therapy approach using a
      recombinant adenovirus carrying human wild-type p53 (WT-p53), granulocyte
      macrophage colony-stimulating factor (GM-CSF) and B7-1 genes (designated BB-102)
      to combat the disease. METHODS: Human malignant glioma cells U251 and U87 were
      transduced with BB-102. Expression of WT-p53, GM-CSF and B7-1 genes were
      determined by Western blot, enzyme linked immunosorbent assay and flow cytometric
      analysis, respectively. Growth rates were determined by serial cell counts.
      Apoptosis was detected by flow cytometric analysis. Proliferation of autologous
      peripheral blood lymphocytes (PBLs) and cytotoxicity against primary glioma cells
      were assessed by cell proliferation and cytotoxicity assay kits, respectively.
      RESULTS: By the transduction of BB-102, high expression levels of the three
      exogenesis genes were detected in glioma cells. Cell growth was inhibited and
      apoptosis was induced. Significant proliferation of autologous PBLs and specific
      cytotoxicity against primary glioma cells were also induced by the infection of
      BB-102 in vitro, with the effect being more evident than that of Ad-p53.
      CONCLUSION: These results suggest that glioma cell vaccination co-transferred
      with p53, GM-CSF and B7-1 genes may be a feasible and effective immunotherapeutic
      approach in glioma treatments.

PMID- 19589205
TI  - A gene delivery system with a human artificial chromosome vector based on
      migration of mesenchymal stem cells towards human glioblastoma HTB14 cells.
AB  - Mesenchymal stem cells (MSCs) have been expected to become useful gene delivery
      vehicles against human malignant gliomas when coupled with an appropriate vector
      system, because they migrate towards the lesion. Human artificial chromosomes
      (HACs) are non-integrating vectors with several advantages for gene therapy,
      namely, no limitations on the size and number of genes that can be inserted. We
      investigated the migration of human immortalized MSCs bearing a HAC vector
      containing the herpes simplex virus thymidine kinase gene (HAC-tk-hiMSCs) towards
      malignant gliomas in vivo. Red fluorescence protein-labeled human glioblastoma
      HTB14 cells were implanted into a subcortical region in nude mice. Four days
      later, green fluorescence protein-labeled HAC-tk-hiMSCs were injected into a
      contralateral subcortical region (the HTB14/HAC-tk-hiMSC injection model).
      Tropism to the glioma mass and the route of migration were visualized by
      fluorescence microscopy and immunohistochemical staining. HAC-tk-hiMSCs began to
      migrate toward the HTB14 glioma area via the corpus callosum on day 4, and
      gathered around the HTB14 glioma mass on day 7. To test whether the delivered
      gene could effectively treat glioblastoma in vivo, HTB14/HAC-tk-hiMSC injected
      mice were treated with ganciclovir (GCV) or PBS. The HTB14 glioma mass was
      significantly reduced by GCV treatment in mice injected with HAC-tk-hiMSCs. It
      was confirmed that gene delivery by our HAC-hiMSC system was effective after
      migration of MSCs to the glioma mass in vivo. Therefore, MSCs containing HACs
      carrying an anticancer gene or genes may provide a new tool for the treatment of
      malignant gliomas and possibly of other tumor types.

PMID- 19589204
TI  - Genetic polymorphisms of low density lipoprotein receptor can modify stroke
      presentation.
AB  - Low density lipoprotein is transcytosed across the blood-brain barrier mediated
      by low density lipoprotein receptor (LDLR). LDLR in the brain is mainly expressed
      on capillary endothelial cells and is therefore considered to be an important
      susceptibility gene in modifying the stroke presentation. A HapMap-based
      haplotype-tagging single nucleotide polymorphism association study was conducted
      in an isolated Taiwanese population. Two hundred and ninety-two unrelated
      patients with cerebral infarction, 76 patients with small vessel occlusion (SVO)
      disorder and 216 with non-SVO disorder were enrolled. For rs2738446, under the
      dominant model, the odds ratios (ORs) associated with the CC genotype were
      computed, with GG + CG carriers considered as the reference group. Homozygote CC
      carriers had a two-fold increased risk of SVO disorder [OR=2.0, 95% confidence
      interval (CI)=1.08-3.70, p=0.025). For rs2738450, under the dominant model, the
      ORs associated with the CC genotype were computed, with AA + AC carriers
      considered as the reference group. Homozygote CC carriers had a 1.85-fold
      increased risk of SVO disorder (OR=1.85, 95% CI=1.01-3.33, p=0.04). When
      analysing the association between the haplotype related to rs2738446 and
      rs2738450 and SVO disorder, the most common haplotype allele CC was used as the
      reference, and the GA haplotype allele was associated with a 48% decreased risk
      of SVO disorder (OR=0.52; 95% CI=0.29-0.93, p=0.029). Haplotype-based analysis of
      LDLR in Taiwanese patients with cerebral infarction provided preliminary evidence
      suggesting that genetic polymorphisms of LDLR can modify the stroke presentation.

PMID- 19589208
TI  - Simultaneous neutron scattering and Raman scattering.
AB  - The capability to make simultaneous neutron and Raman scattering measurements at
      temperatures between 1.5 and 450 K has been developed. The samples to be
      investigated are attached to one end of a custom-made center-stick suitable for
      insertion into a 100 mm-bore cryostat. The other end of the center-stick is fiber
      optically coupled to a Renishaw in Via Raman spectrometer incorporating a 300 mW
      Toptica 785 nm wavelength stabilized diode laser. The final path for the laser
      beam is approximately 1.3 m in vacuo within the center-stick followed by a
      focusing lens close to the sample. Raman scattering measurements with a
      resolution of 1 to 4 cm(-1) can be made over a wide range (100-3200 cm(-1)) at
      the same time as a variety of different types of neutron scattering measurements.
      In this work we highlight the use of inelastic neutron scattering and neutron
      diffraction in conjunction with the Raman for studies of the globular protein
      lysozyme.

PMID- 19589209
TI  - Predicting Raman spectra using density functional theory.
AB  - Accurately computing molecular Raman spectra would enable rapid development of
      inexpensive and extensive Raman libraries. This is especially beneficial for
      chemicals that are regulated, toxic, or otherwise difficult to handle. Numerous
      quantum mechanical methods have been developed that enable computation of Raman
      spectra. Here, we study the B3LYP exchange correlation functional with various
      combinations of basis sets, polarization functions, and diffuse functions to
      determine which combination best computes the Raman spectra for explosive and
      nonexplosive molecules. In comparing spectra, three metrics were utilized: the
      root mean square error, the earth mover's distance, and the weighted cross
      correlation average. The earth mover's distance and weighted cross-correlation
      metrics are shown to have significantly greater power at detecting spectral
      similarities and differences than the root mean square error. Across all methods
      and molecules examined, B3LYP/6-311++G(d,p) was found to provide the best match
      between measured and computed Raman spectra. Spectra generated at the B3LYP/6
      311++G(d,p) level were found to be accurate enough to correctly identify each
      molecule out of a set of measured molecular spectra.

PMID- 19589211
TI  - The effect of synthesis temperature on the formation of hydrotalcites in Bayer
      liquor: a vibrational spectroscopic analysis.
AB  - The seawater neutralization process is currently used in the alumina industry to
      reduce the pH and dissolved metal concentrations in bauxite refinery residues
      through the precipitation of Mg, Al, and Ca hydroxide and carbonate minerals.
      This neutralization method is very similar to the co-precipitation method used to
      synthesize hydrotalcite (Mg6Al2(OH)16CO3.4H2O). This study looks at the effect of
      temperature on the type of precipitates that form from the seawater
      neutralization process of Bayer liquor. The Bayer precipitates have been
      characterized by a variety of techniques, including X-ray diffraction (XRD),
      Raman spectroscopy, and infrared spectroscopy. The mineralogical composition of
      Bayer precipitates largely includes hydrotalcite, hydromagnesite, and calcium
      carbonate species. Analysis with XRD determined that Bayer hydrotalcites that are
      synthesized at 55 degrees C have a larger interlayer distance, indicating that
      more anions are removed from Bayer liquor. Vibrational spectroscopic techniques
      have identified an increase in hydrogen bond strength for precipitates formed at
      55 degrees C, suggesting the formation of a more stable Bayer hydrotalcite. Raman
      spectroscopy identified the intercalation of sulfate and carbonate anions into
      Bayer hydrotalcites using these synthesis conditions.

PMID- 19589210
TI  - Rapid classification of simulated street drug mixtures using Raman spectroscopy
      and principal component analysis.
AB  - The ability to accurately and noninvasively analyze illicit drugs is important
      for criminal investigations and prosecution. Current methods involve significant
      sample pretreatment and most are destructive. The goal of this work is to develop
      a method based on Raman spectroscopy to classify simulated street drug mixtures
      composed of one drug component and up to three cutting agents including those
      routinely found in confiscated illicit street drug mixtures. Spectra were
      collected on both a homebuilt instrument using a HeNe laser and on a handheld
      commercial instrument with a 785 nm light source. Mixtures were prepared with
      drug concentrations ranging from 10 to 100 percent. Optimal preprocessing for the
      data set included truncating, Savitzky-Golay smoothing, normalization,
      differentiating, and mean centering. Using principal component analysis (PCA), it
      was possible to resolve the spectral differences between benzocaine, lidocaine,
      isoxsuprine, and norephedrine and correctly classify them 100 percent of the
      time.

PMID- 19589212
TI  - Near-infrared spectroscopic investigation of the hydrothermal degradation
      mechanism of wood as an analogue of archaeological wood. Part II: hardwood.
AB  - Near-infrared (NIR) spectroscopy and chemometrics were applied to analyze the
      degradation mechanism of hardwood following hydrothermal treatment. NIR spectra,
      chemical composition, oven-dried density, equilibrium moisture content,
      compressive Young's modulus parallel to grain, and cellulose crystallinity of
      artificially degraded beech as an analogue of archaeological wood were
      systematically measured. Partial least squares (PLS) regression analysis was
      employed to predict compressive Young's modulus using NIR spectra and various
      properties as independent variables. Results are also compared with previous data
      obtained from similar treatment of softwood (Hinoki cypress). The increase in
      cellulose crystallinity of hardwood during the initial stage of hydrothermal
      treatment (up to 5 hours) was correlated with an improvement in the mechanical
      properties of wood. Young's modulus for both hardwood and softwood showed a
      gradual decrease over five hours of hydrothermal treatment, which is proposed to
      be due to the degradation of polysaccharide.

PMID- 19589213
TI  - Attenuated total internal reflection Fourier transform infrared spectroscopy: a
      quantitative approach for kidney stone analysis.
AB  - The impact of kidney stone disease is significant worldwide, yet methods for
      quantifying stone components remain limited. A new approach requiring minimal
      sample preparation for the quantitative analysis of kidney stone components has
      been investigated utilizing attenuated total internal reflection Fourier
      transform infrared spectroscopy (ATR-FT-IR). Calcium oxalate monohydrate (COM)
      and hydroxylapatite (HAP), two of the most common constituents of urinary stones,
      were used for quantitative analysis. Calibration curves were constructed using
      integrated band intensities of four infrared absorptions versus concentration
      (weight %). The correlation coefficients of the calibration curves range from
      0.997 to 0.93. The limits of detection range from 0.07 +/- 0.02% COM/HAP where
      COM is the analyte and HAP is the matrix, to 0.26 +/- 0.07% HAP/COM where HAP is
      the analyte and COM is the matrix. This study shows that linear calibration
      curves can be generated for the quantitative analysis of stone mixtures provided
      the system is well understood especially with respect to particle size.

PMID- 19589214
TI  - Spectroscopic characterization of the SH2- and active site-directed peptide
      sequences of a bivalent Src kinase inhibitor.
AB  - The spectral properties of the SH2 and active site-directed sequences of the
      bivalent Src kinase inhibitor Ac-EELL(F5)Phe-(GABA)3-pYEEIE-amide (1) have been
      determined. Ac-pYEEIE-amide (2) and AcEELL(F5)Phe-amide (3), as well as the amino
      acids phosphotyrosine (pTyr) and pentafluorophenylalanine (F5)Phe, have been
      characterized by electronic absorption, fluorescence, and vibrational
      spectroscopy. Specific and unique marker bands that originate from the phosphate
      group of pTyr and the fluorinated aromatic ring of (F5)Phe have been identified,
      with the latter showing some solvent dependence. Peptide 2 was found to have
      excitation and emission wavelengths emanating from pTyr at 268 and 295 nm,
      respectively, whereas peptide 3 displayed excitation and emission peaks
      attributable to (F5)Phe at 274 and 315 nm, respectively. Fourier transform
      infrared (FT-IR) analysis of the amino acid pTyr identified distinct marker bands
      at approximately 930, 1090, and 1330 cm(-1) that could be attributed to the
      phosphate group. These markers were also observed in the IR spectrum of peptide
      2. Likewise, peptide 3 displayed a characteristic C-F stretching mode at 961 cm(
      1) due to the presence of (F5)Phe, including two C-F reporting ring modes at 1509
      and 1527 cm(-1). Identifying and monitoring spectroscopic changes in these marker
      bands may afford a means to observe the molecular interactions that occur when
      peptides 1-3 bind to the Src kinase.

PMID- 19589215
TI  - Comparison of vibrational circular dichroism instruments: development of a new
      dispersive VCD.
AB  - A dispersive vibrational circular dichroism (VCD) instrument has been designed
      and optimized for the measurement of mid-infrared (MIR) bands such as the amide I
      and amide II vibrational modes of peptides and proteins. The major design
      considerations were to construct a compact VCD instrument for biological
      molecules, to increase signal-to-noise (S/N) ratio, to simultaneously collect and
      digitize the sample transmission and polarization modulation signals, and to
      digitally ratio them to yield a VCD spectrum. These were realized by assembling
      new components using design factors adapted from previous VCD instruments. A
      collection of spectra for peptides and proteins having different dominant
      secondary structures (alpha-helix, beta-sheet, and random coil) measured for
      identical samples under the same conditions showed that the new instrument had
      substantially improved S/N as compared with our previous dispersive VCD
      instrument. These instruments both provide protein VCD for the amide I that are
      comparable to or somewhat better than those measurable with commercial Fourier
      transform (FT) VCD instruments if just the amide I band in the spectra is
      obtained at modest resolution (8 cm(-1)) with the same total data collection time
      on each type of instrument.

PMID- 19589216
TI  - Reconstruction method and optimal design of an interferometric spectrometer.
AB  - In this paper, we present a method to estimate the power spectral distribution of
      a source from input data acquired by an interferometric-based spectrometer. Our
      spectrometer shows distortions in the fringe pattern and a lack of data, making
      it impossible to apply the Fourier transform approach, which is the gold standard
      as a spectral recovery method for interferometric spectrometers. We combined
      linear inverse problem solving and iterative methods instead, considering that
      each detector of the spectrometer has a specific and known spectral response.
      Iterative methods are used to overcome problems caused by lack of input data. We
      show that a good spectral estimation of relatively simple spectra having a
      resolution of 400 points is typically achieved using fewer than 10 detectors with
      such a method. Since the quality of spectral restitution with such an approach
      relies both on signal processing and an optimal selection of the detector's
      spectral responses, the paper also shows that some sets of spectral responses
      selected for the detection and consequently a spectral repartition of the
      detectors are more successful than others in the spectral recovery process. We
      chose the condition number of the inversion matrix as an optimization criterion
      and evaluated how this criterion can be used within this framework. We found that
      maximizing it achieves better spectral restitution, within a range where noise
      remains low.

PMID- 19589217
TI  - The role and selection of the filter function in Fourier self-deconvolution
      revisited.
AB  - Overlapped bands often appear in applications of infrared spectroscopy, for
      instance in the analysis of the amide I band of proteins. Fourier self
      deconvolution (FSD) is a popular band-narrowing mathematical method, allowing for
      the resolution of overlapped bands. The filter function used in FSD plays a
      significant role in the factor by which the deconvolved bands are actually
      narrowed (the effective narrowing), as well as in the final signal-to-noise
      degradation induced by FSD. Moreover, the filter function determines, to a good
      extent, the band-shape of the deconvolved bands. For instance, the intensity of
      the harmful side-lobule oscillations that appear in over-deconvolution depends
      importantly on the filter function used. In the present paper we characterized
      the resulting band shape, effective narrowing, and signal-to-noise degradation in
      infra-, self-, and over-deconvolution conditions for several filter functions:
      Triangle, Bessel, Hanning, Gaussian, Sinc2, and Triangle2. We also introduced and
      characterized new filters based on the modification of the Blackmann filter. Our
      conclusion is that the Bessel filter (in infra-, self-, and mild over
      deconvolution), the newly introduced BL3 filter (in self- and mild/moderate over
      deconvolution), and the Gaussian filter (in moderate/strong over-deconvolution)
      are the most suitable filter functions to be used in FSD.

PMID- 19589218
TI  - Calibration maintenance and transfer using Tikhonov regularization approaches.
AB  - Maintaining multivariate calibrations is essential and involves keeping models
      developed on an instrument applicable to predicting new samples over time.
      Sometimes a primary instrument model is needed to predict samples measured on
      secondary instruments. This situation is referred to as calibration transfer.
      This paper reports on using a Tikhonov regularization (TR) based method in both
      cases. A distinction of the TR design for calibration maintenance and transfer is
      a defined weighting scheme for a small set of new (transfer or standardization)
      samples augmented to the full set of calibration samples. Because straight
      application of basic TR theory is not always possible with calibration
      maintenance and transfer, this paper develops a generic solution to always enable
      application of TR. Harmonious (bias/variance tradeoff) and parsimonious
      (effective rank) considerations for TR are compared with the same TR format
      applied to partial least squares (PLS), showing that both approaches are viable
      solutions to the calibration maintenance and transfer problems.

PMID- 19589219
TI  - A similarity measure for two-dimensional fluorescent spectra.
AB  - A similarity measure was developed that can differentiate between two-dimensional
      fluorescent spectra based on their similarities and differences. The two
      dimensional fluorescent spectra are digitalized into matrices. The difference
      between the two spectra is defined by a difference matrix, whose elements contain
      the difference of one two-dimensional fluorescent spectrum minus the other. The
      similarity measure is transformed into hypothesis tests of the similarity and
      difference between the two spectra. The scalar mean of the difference matrix is
      used as the statistical variable for the hypothesis test. The Bayesian prior odds
      ratio was estimated from multiple spectra of the same reference sample. A
      threshold for the hypothesis test that the spectra are different is proposed. The
      posterior odds ratio was used to quantify the similarity measure of the two
      spectra. Two-dimensional fluorescent spectra of Changyu red wine samples were
      used to demonstrate this method. The results show that this new method can detect
      differences between the spectra.

PMID- 19589220
TI  - Pulsed laser excited photothermal lens spectrometry of CdSxSe(1-x) doped silica
      glasses.
AB  - Experimental results for photothermal lens measurements are compared to finite
      elemental analysis models for commercial colored glass filters. Finite elemental
      analysis software is used to model the photothermal effect by simulating the
      coupling of heat both within the sample and out to the surroundings. Modeling
      shows that heat transfer between the glass surface and the air coupling fluid has
      a significant effect on the predicted time-dependent photothermal lens signals.
      For comparison with experimental signals, a simple equation based on the finite
      element analysis result is proposed for accounting for the variance of
      experimental data where this type of heat coupling situation occurs. The colored
      glass filters are found to have positive thermo-optical coefficients. The net
      positive dn/dT of CdSxSe(1-x) doped glass filters is considered to be the
      consequence of counteracting factors: optical nonlinearity, stress-induced
      birefringence, and the structural network of glass. Finite element analysis
      modeling results are also used to correlate experimental measurements of
      different sample geometries. In particular, the glass samples are compared to
      ethanol solutions of iron (II) dicylopentadiene in a sample cuvette even though
      heat transfer is different for these two samples.

PMID- 19589221
TI  - Spectroscopic study of an expanded argon microwave (2.45 GHz) plasma at
      atmospheric pressure in a helium environment.
AB  - In the present work, an argon microwave (2.45 GHz) plasma flame created at the
      end of a surface-wave-sustained discharge column in a helium environment has been
      experimentally studied. This is a plasma with new possibilities because under
      some experimental conditions it expands, being less contracted than the plasma
      flame created in open air. The new expanded discharge could offer additional
      advantages for applications in which larger extensions of plasma were required.
      The expansion phenomenon of this plasma flame was studied under different
      experimental conditions. In every case, the characteristic parameters of this
      expanded plasma such as electron density, electron and gas temperatures, or
      density population of excited atomic levels were measured by using optical
      emission spectroscopic techniques. From these results, the main advantages of
      this plasma source were pointed out.

PMID- 19589223
TI  - Minimally destructive and multi-element analysis of steel alloys by argon
      fluoride laser-induced plume emissions.

PMID- 19589224
TI  - Neuropharmacological and pharmacokinetic properties of berberine: a review of
      recent research.
AB  - OBJECTIVES: This review summarizes recent research on the neuropharmacological
      and pharmacokinetic properties of berberine, an isoquinoline alkaloid extracted
      from Coptidis rhizoma. KEY FINDINGS: Berberine has multiple neuropharmacological
      properties, such as neuroprection, anti-neuronal apoptosis, improvement of
      cerebral microcirculation and anti-Alzheimer's disease, and so on. The
      pharmacokinetic characteristics of berberine are that it is not easily absorbed
      and it is not stable in the gastrointestinal tract of animals or humans. SUMMARY:
      Further studies need to be carried out to develop berberine as a drug for nervous
      system diseases, such as brain ischaemia and Alzheimer's disease, that has
      favorable pharmacokinetic properties.

PMID- 19589222
TI  - Raman microscopic applications in the biopharmaceutical industry: in situ
      identification of foreign particulates inside glass containers with aqueous
      formulated solutions.
AB  - Particle identification is an important analytical procedure for quality control
      and assurance in the biopharmaceutical industry. Rapid and reliable
      identification of micro-particles helps in evaluating the nature of particle
      contamination and its consequences on the product quality regulated by internal
      and external standards. Raman microscopy is one of the microspectroscopic
      techniques that can be used to identify micro-particles with the advantage of in
      situ detection. In this paper we demonstrate that a visible laser Raman
      microscope was particularly useful to identify micro-particles that were inside
      glass containers such as glass syringes, vials, and test tubes, which are
      commonly used as containers for aqueous formulated drugs. The examples include
      the identifications of a droplet-like particle inside a pre-filled glass syringe,
      a fibrous particle inside a glass test tube, and a white particle inside a glass
      vial; all of these examples usually demand challenging or time-consuming sample
      manipulation for other techniques. The Raman microscopic technique was shown to
      be able to solve these challenging micro-particle identifications due to its
      ability to carry out detection in situ. Particularly in the example of micro
      droplet identification, the Raman microscopic technique was the only choice for a
      fast and successful particle detection. For all three identifications, Raman in
      situ detection has significantly accelerated particle analysis and avoided
      potential sample secondary contamination or losses owing to none or minimal
      sample manipulation.

PMID- 19589225
TI  - Cannabinoid receptor ligands as potential anticancer agents--high hopes for new
      therapies?
AB  - OBJECTIVES: The endocannabinoid system is an endogenous lipid signalling network
      comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors,
      transporters and endocannabinoid degrading enzymes. The CB(1) receptor is
      predominantly expressed in neurons but is also co-expressed with the CB(2)
      receptor in peripheral tissues. In recent years, CB receptor ligands, including
      Delta(9)-tetrahydrocannabinol, have been proposed as potential anticancer agents.
      KEY FINDINGS: This review critically discusses the pharmacology of CB receptor
      activation as a novel therapeutic anticancer strategy in terms of ligand
      selectivity, tissue specificity and potency. Intriguingly, antitumour effects
      mediated by cannabinoids are not confined to inhibition of cancer cell
      proliferation; cannabinoids also reduce angiogenesis, cell migration and
      metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the
      last decade several new selective CB(1) and CB(2) receptor agents have been
      described, but most studies in the area of cancer research have used non
      selective CB ligands. Moreover, many of these ligands exert prominent CB receptor
      independent pharmacological effects, such as activation of the G-protein-coupled
      receptor GPR55, peroxisome proliferator-activated receptor gamma and the
      transient receptor potential vanilloid channels. SUMMARY: The role of the
      endocannabinoid system in tumourigenesis is still poorly understood and the
      molecular mechanisms of cannabinoid anticancer action need to be elucidated. The
      development of CB(2)-selective anticancer agents could be advantageous in light
      of the unwanted central effects exerted by CB(1) receptor ligands. Probably the
      most interesting question is whether cannabinoids could be useful in
      chemoprevention or in combination with established chemotherapeutic agents.

PMID- 19589226
TI  - Enhanced skin delivery of quercetin by microemulsion.
AB  - OBJECTIVES: For topical application of quercetin it is necessary to improve the
      low efficiency of its intradermal delivery as well as its low solubility in
      aqueous and organic vesicles. The aim of this study was to determine the
      usefulness of a microemulsion for that purpose. METHODS: A microemulsion
      consisting of isopropyl myristate, 150 mM NaCl solution, Tween 80 and ethanol was
      prepared. The skin delivery of quercetin by microemulsion using excised guinea
      pig and Yucatan micropig skin in Franz diffusion cells was examined. Lipid
      peroxidation in skin was also tested using iron(II) and citrate. KEY FINDINGS:
      Using a w/o microemulsion as a vehicle, intradermal delivery of quercetin was
      significantly increased, as was its solubility. Quercetin penetrated deep into
      the skin, but no transfer was observed into the receptor compartment. It was
      confirmed that quercetin retained in the skin dose-dependently inhibited lipid
      peroxidation. CONCLUSIONS: The findings indicate the potential use of
      microemulsions for the skin delivery of quercetin, where it exerts antioxidative
      effects.

PMID- 19589227
TI  - Application of a novel symmetrical shape factor to gastroretentive matrices as a
      measure of swelling synchronization and its impact on drug release kinetics under
      standard and modified dissolution conditions.
AB  - OBJECTIVES: We have assessed the kinetics of drug release in relation to the full
      or partial hydration and swelling of matrices under standard and modified United
      States Pharmacopeia (USP) apparatus II using a novel index, defined as the
      symmetrical shape factor. The symmetrical shape factor describes the regularity
      of the hydration rate of the matrix perimeter relative to its central regions.
      METHODS: Monolithic and three-layer matrices based on hypromellose, polyethylene
      oxide, Kollidon SR, theophylline, diltiazem hydrochloride and alfuzosin
      hydrochloride were subjected to dissolution testing. KEY FINDINGS: Our results
      indicated that Kollidon SR matrices and the three-layer composite systems with
      and without effervescing components were not significantly affected by the
      dissolution conditions. However, in the case of the floating monolithic systems
      based on hypromellose and polyethylene oxide, both release profiles and swelling
      dynamics in accordance with the similarity factor (f(2)) and symmetrical shape
      factor values were significantly influenced. CONCLUSIONS: The symmetrical shape
      factor values were positively impacted. Consequently the drug release kinetics
      were more predictable and reproducible. The modified USP method resulted in a
      more synchronized axial and radial swelling with symmetrical shape factor values
      approaching unity. Data further indicated that the modified USP method provided
      for complete matrix hydration and swelling as the dosage form remained fully
      submerged, allowing for more reliable release mimicking the in-vivo conditions.

PMID- 19589228
TI  - Preparation and in-vitro bioactivity of a novel superantigen conjugate targeting
      bladder carcinoma.
AB  - OBJECTIVES: Superantigens have shown potent effects against bladder tumours by
      inducing Vbeta-specific T-lymphocyte proliferation and massive cytokine release
      but therapeutic benefit is compromised by cytotoxicity towards non-malignant
      cells and hypotoxicity to major histocompability complex (MHC) II-negative tumour
      cells. We are therefore interested in a conjugate preparation of a monoclonal
      antibody (MAb)-superantigens conjugate for which these drawbacks would be
      resolved. METHODS: The Fab fragment of the anti-bladder carcinoma MAb BDI-1 was
      conjugated to one member of the staphylococcal enterotoxin A (SEA) superantigen
      using the chemical conjugating reagent, N-succinimidyl 3-(2-pyridyldithio)
      propionate. RESULTS: After HPLC purification through a Superdex-200 gel column,
      another peak with a molecular mass of 250 KDa was observed before Fab and SEA
      were eluted. Indirect immunocytochemical analysis and immunofluorescence tests
      showed that the cell membranes of most human bladder cancer cells were positively
      stained only by the conjugate, confirming the ability of the conjugate to target
      human bladder carcinoma. Peripheral blood mononuclear cell proliferation and
      cytokine release were similar with the conjugate and SEA. Cytotoxicity targeting
      in MHC II-negative bladder cancer cell lines, evaluated by flow cytometry, showed
      significant differences between the conjugate and SEA, whereas there was no
      difference in the Lovo colon cancer cell line. CONCLUSIONS: These findings
      indicate the conjugate of SEA protein and BDI-1 Fab fragment was prepared
      successfully and targeted bladder carcinoma in vitro.

PMID- 19589229
TI  - Metabolic interactions with piperazine-based 'party pill' drugs.
AB  - OBJECTIVES: 'Party pills' have found use worldwide as a substitute for
      amphetamine-derived designer drugs. Whilst some information exists about the
      metabolism of these drugs, there is little information about their ability to
      inhibit the metabolism of co-administered drugs. This study aimed to determine
      whether predictions can be made about global interactions between 'party pills'
      constituents and other drugs metabolised by the same cytochrome P450 (CYP)
      isoenzymes. METHODS: The inhibitory effects of seven benzyl and phenyl
      piperazines were measured in microsomal incubation assays of probe substrates for
      five major CYP isoenzymes. In addition, the metabolism of benzylpiperazine and
      trifluoromethylphenylpiperazine, the two most commonly used constituents of
      'party pills', was investigated using human liver microsomes assays and known
      inhibitors of CYP isoenzymes. KEY FINDINGS: All piperazine analogues tested
      showed significant inhibitory activity against most, if not all, isoenzymes
      tested. The metabolism of benzylpiperazine (BZP) and
      trifluoromethylphenylpiperazine (TFMPP) involved CYP2D6, CYP1A2 and CYP3A4.
      Furthermore, BZP and TFMPP inhibited each other's metabolism. CONCLUSIONS:
      Fluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine,
      methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant
      inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but
      each piperazine had a different inhibitory profile. The metabolic interaction
      between BZP and TFMPP may have clinical implications, as these agents are often
      combined in 'party pills'.

PMID- 19589230
TI  - An improved primary human nasal cell culture for the simultaneous determination
      of transepithelial transport and ciliary beat frequency.
AB  - OBJECTIVES: The aim was to establish a preclinical in-vitro system of the nasal
      mucosa for the simultaneous evaluation of nasal absorption and effects on ciliary
      activity. METHODS: Human nasal epithelial cells were grown in collagen-coated
      transport inserts with transparent polyethylene terephthalate membranes (3 mum).
      Transepithelial transport and ciliary beat frequency values were measured every
      15 min for 1 h. KEY FINDINGS: The apparent permeability coefficients (P(app)) for
      atenolol (mainly paracellular transport) and propranolol (transcellular
      transport) amounted to 0.1 +/- 0.1 and 23.7 +/- 0.6 x 10(-6) cm/s, respectively,
      illustrating that the system can be used to discriminate between high
      permeability and low permeability compounds. Transport of talinolol (substrate
      for the P-glycoprotein efflux carrier) did not reveal polarity (0.3 +/- 0.2 and
      0.2 +/- 0.1 x 10(-6) cm/s for absorptive and secretory transport, respectively)
      and was not affected by verapamil (10 muM), suggesting the absence of P
      glycoprotein in the nasal cell culture. No significant effects of atenolol,
      propranolol and talinolol on ciliary beat frequency were observed (98 +/- 20% of
      the control condition after 60 min). Chlorocresol significantly decreased the
      ciliary activity but this decrease was not accompanied by effects on the
      transepithelial transport of atenolol, propranolol and talinolol. CONCLUSIONS: A
      new system was developed which offers possibilities as a fast screening tool for
      studying the potential of compounds for nasal drug administration, since
      permeability and a possible cilio-toxic effect can be assessed simultaneously.

PMID- 19589231
TI  - Whole-body physiologically based pharmacokinetic population modelling of oral
      drug administration: inter-individual variability of cimetidine absorption.
AB  - OBJECTIVES: Inter-individual variability of gastrointestinal physiology and
      transit properties can greatly influence the pharmacokinetics of an orally
      administered drug in vivo. To predict the expected range of pharmacokinetic
      plasma concentrations after oral drug administration, a physiologically based
      pharmacokinetic population model for gastrointestinal transit and absorption was
      developed and evaluated. METHODS: Mean values and variability measures of model
      parameters affecting the rate and extent of cimetidine absorption, such as
      gastric emptying, intestinal transit times and effective surface area of the
      small intestine, were obtained from the literature. Various scenarios
      incorporating different extents of inter-individual physiological variability
      were simulated and the simulation results were compared with experimental human
      study data obtained after oral cimetidine administration of four different
      tablets with varying release kinetics. KEY FINDINGS: The inter-individual
      variability in effective surface area was the largest contributor to absorption
      variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine
      concentration-time profiles as well as the inter-individual variability could be
      well described for three cimetidine formulations. In the case of the formulation
      with the slowest dissolution kinetic, model predictions on the basis of the in
      vitro dissolution profile underestimated the plasma exposure. CONCLUSIONS: The
      model facilitates predictions of the inter-individual pharmacokinetic variability
      after oral drug administration for immediate and extended-release formulations of
      cimetidine, given reasonable in-vitro dissolution kinetics.

PMID- 19589232
TI  - Interaction of morphine but not fentanyl with cerebral alpha2-adrenoceptors in
      alpha2-adrenoceptor knockout mice.
AB  - OBJECTIVES: alpha(2)-Adrenergic and mu-opioid receptors belong to the rhodopsin
      family of G-protein coupled receptors and mediate antinociceptive effects via
      similar signal transduction pathways. Previous studies have revealed direct
      functional interactions between both receptor systems including synergistic and
      additive effects. To evaluate underlying mechanisms, we have studied whether
      morphine and fentanyl interacted with alpha(2)-adrenoceptor-subtypes in mice
      lacking one individual alpha(2)-adrenoceptor-subtype (alpha(2)-adrenoceptor
      knockout). METHODS: Opioid interaction with alpha(2)-adrenoceptors was
      investigated by quantitative receptor autoradiography in brain slices of
      alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of
      the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]paraiodoclonidine from
      alpha(2)-adrenoceptors in different brain regions by increasing concentrations of
      morphine, fentanyl and naloxone was analysed. The binding affinity of both
      opioids to alpha(2)-adrenoceptor subtypes in different brain regions was
      quantified. KEY FINDINGS: Morphine but not fentanyl or naloxone provoked dose
      dependent displacement of [(125)I]paraiodoclonidine from all alpha(2)
      adrenoceptor subtypes in the brain regions analysed. Binding affinity was highest
      in cortex, medulla oblongata and pons of alpha(2A)-adrenoceptor knockout mice.
      CONCLUSIONS: Our results indicated that morphine interacted with alpha(2)
      adrenoceptors showing higher affinity for the alpha(2B) and alpha(2C) than for
      the alpha(2A) subtype. In contrast, fentanyl and naloxone did not show any
      relevant affinity to alpha(2)-adrenoceptors. This effect may have an impact on
      the pharmacological actions of morphine.

PMID- 19589233
TI  - Site-specific contribution of proton-coupled folate transporter/haem carrier
      protein 1 in the intestinal absorption of methotrexate in rats.
AB  - OBJECTIVES: Methotrexate is reportedly a substrate for proton-coupled folate
      transporter/haem carrier protein 1 (PCFT/HCP1) and reduced folate carrier 1
      (RFC1). In this study, we examined the contribution of PCFT/HCP1 and RFC1 in the
      intestinal absorption of methotrexate in rats. METHODS: Western blot analysis was
      carried out to evaluate the protein levels of PCFT/HCP1 and multidrug resistance
      associated protein 2 in brush-border membrane of rat small intestine. Mucosal
      uptake of methotrexate was studied in the rat everted small intestine and an in
      situ intestinal perfusion study of methotrexate was also carried out in rats. KEY
      FINDINGS: In transport studies using everted intestine, the mucosal methotrexate
      influx rate in proximal intestine at pH 5.5 was significantly greater than that
      at pH 7.4. Coadministration of folate or its analogues, such as folinate and 5
      methyltetrahydrofolate, substrates for both PCFT/HCP1 and RFC1, significantly
      suppressed the methotrexate influx at pH 5.5, whereas thiamine pyrophosphate, an
      inhibitor for RFC1 alone, exerted no significant effect. Western blot analysis
      showed higher PCFT/HCP1 expression in proximal than distal small intestine. In
      distal small intestine, methotrexate influx rate was low and was not pH
      dependent. Also, folate and its analogues exerted no significant effect on
      methotrexate absorption. CONCLUSIONS: Based on the present and our previous
      results, the site-specific contributions of various transporters including
      PCFT/HCP1 in methotrexate intestinal absorption were discussed. The variation in
      luminal pH and the involvement of multiple transporters in methotrexate
      absorption may cause variation in oral bioavailability among patients.

PMID- 19589234
TI  - Hexa-, hepta- and nonaprenylhydroquinones isolated from marine sponges
      Sarcotragus muscarum and Ircinia fasciculata inhibit NF-kappaB signalling in
      H4IIE cells.
AB  - OBJECTIVES: Marine organisms have proven to be a rich source of potent
      pharmacologically active compounds. Three polyprenyl-1,4-hydroquinone derivates
      (hexaprenyl-1,4-hydroquinone, heptaprenyl-1,4-hydroquinone and nonaprenyl-1,4
      hydroquinone) were isolated from the Zoobenthos-inhabiting sponges Sarcotragus
      muscarum and Ircinia fasciculata from the Eastern Mediterranean Sea (phylum:
      Porifera; class: Demospongiae). METHODS: Hexa-, hepta- and nonaprenylhydroquinone
      were identified by (1)H-NMR, H,H-COSY, heteronuclear multiple bond correlation,
      FAB-MS and UV spectroscopy. The effects of the compounds on cell viability was
      determined using the MTT assay; anti-oxidative potential was measured using the
      Trolox equivalent antioxidative capacity assay. Inhibition of nuclear factor
      kappaB activity was detected by secreted alkaline phosphatase assay. Activity
      against an array of protein kinases was determined in 96-well FlashPlates. KEY
      FINDINGS: All compounds had prominent antioxidative activity, comparable to that
      of the synthetic vitamin E derivate Trolox. Hexaprenylhydroquinone showed the
      greatest cytotoxicity in H4IIE hepatoma cells (EC50 2.5 muM). All three compounds
      inhibited NF-kappaB signalling in this cell line, with heptaprenylhydroquinone
      being the most active. Screening of 23 kinases involved in signal transduction
      pathways (cell proliferation, survival, angiogenesis and metastasis) showed that
      hexaprenylhydroquinone and heptaprenylhydroquinone inhibited the activity of the
      epidermal growth factor receptor (IC50 1.6 and 1.4 mug/ml, respectively), and
      heptaprenylhydroquinone also inhibited the activity of other kinases (Src
      tyrosine kinase, vascular endothelial growth factor receptor 3 and insulin-like
      growth factor 1 receptor). CONCLUSIONS: The prenylated hydroquinones isolated
      from the marine sponges S. muscarum and I. fasciculata showed cytotoxic and
      antioxidative activities and inhibited NF-kappaB signalling in H4IIE hepatoma
      cells and protein kinases. These findings may result in the generation of new
      lead substances in cancer therapy.

PMID- 19589235
TI  - Protection afforded by a herbal medicine, Sho-seiryu-to (TJ-19), against oleic
      acid-induced acute lung injury in guinea-pigs.
AB  - OBJECTIVES: The effect of a herbal medicine, Sho-seiryu-to (TJ-19), on oleic acid
      induced lung injury, an animal model of acute respiratory distress syndrome or
      acute lung injury (ARDS/ALI), was examined. METHODS: Acute lung injury was
      induced by an intravenous injection of 15 microl/kg oleic acid to guinea-pigs. TJ
      19 was administered by a single oral dose (3 g/kg) or by multiple oral doses
      (0.75 g/kg). KEY FINDINGS: The decrease in partial oxygen pressure of arterial
      blood (Pao(2)) and the increase in airway vascular permeability induced by the
      oleic acid injection were attenuated by a single dose of TJ-19. When TJ-19 was
      administered orally twice a day for two weeks and then oleic acid was injected, a
      potent prophylactic effect of the drug was observed. TJ-19 also prevented airway
      vascular hyperpermeability, lung cell injury, oxidative stress and thromboxane
      A(2) generation, associated with the oleic acid injection. CONCLUSIONS: TJ-19
      significantly attenuated the oleic acid-induced lung injury probably through the
      antioxidative effect and inhibitory effect of thromboxane A(2) generation,
      although the precise inhibitory mechanisms were not fully elucidated due to the
      diversity in constituents of the herbal medicine. We suggest that TJ-19 is a
      promising drug candidate and a medicinal resource for preventing ARDS/ALI.

PMID- 19589236
TI  - The role of polar phytocomplexes on anticonvulsant effects of leaf extracts of
      Lippia alba (Mill.) N.E. Brown chemotypes.
AB  - OBJECTIVES: The purpose of the present work was to characterize the
      pharmacological profile of different L. alba chemotypes and to correlate the
      obtained data to the presence of chemical constituents detected by phytochemical
      analysis. METHODS: Essential oils from each L. alba chemotype (LP1-LP7) were
      characterized by gas chromatography-mass spectrometry (GC-MS) and extracted non
      volatile compounds were analysed by HPLC and GC-MS. The anticonvulsant actions of
      the extracted compounds were studied in pentylenetetrazole-induced clonic
      seizures in mice and their effect on motor coordination was studied using the
      rota-rod test in rats. The synaptosomes and synaptic membranes of the rats were
      examined for the influence of LP3 chemotype extract on GABA uptake and binding
      experiments. KEY FINDINGS: Behavioural parameters encompassed by the
      pentylenetetrazole test indicated that 80% ethanolic extracts of LP1, LP3 and LP6
      L. alba chemotypes were more effective as anticonvulsant agents. Neurochemical
      assays using synaptosomes and synaptic membranes showed that L. alba LP3
      chemotype 80% ethanolic extract inhibited GABA uptake and GABA binding in a dose
      dependent manner. HPLC analysis showed that LP1, LP3 and LP6 80% ethanolic
      extracts presented a similar profile of constituents, differing from those seen
      in LP2, LP4, LP5 and LP7 80% ethanolic extracts, which exhibited no
      anticonvulsant effect. GC-MS analysis indicated the occurrence of
      phenylpropanoids in methanolic fractions obtained from LP1, LP3 and LP6 80%
      ethanolic extracts and also the accumulation of inositol and flavonoids in
      hydroalcoholic fractions. CONCLUSIONS: Our results suggest that the
      anticonvulsant properties shown by L. alba might be correlated to the presence of
      a complex of non-volatile substances (phenylpropanoids, flavonoids and/or
      inositols), and also to the volatile terpenoids (beta-myrcene, citral, limonene
      and carvone), which have been previously validated as anticonvulsants.

PMID- 19589237
TI  - Protection of DNA and membranes from gamma-radiation induced damages by Centella
      asiatica.
AB  - OBJECTIVES: The objective of the present study was to examine the ability of
      Centella asiatica extract to offer protection to DNA and membranes against the
      deleterious effects of ionizing radiation exposure. METHODS: Protection of DNA
      under in-vitro conditions of irradiation was estimated using plasmid relaxation
      assay. For in-vivo studies the extract was administered orally to mice exposed to
      whole-body gamma-radiation. The ability of the extract to offer protection
      against whole-body gamma-radiation exposure was analysed by performing an
      alkaline comet assay on mouse bone marrow cells. The extent of lipid peroxidation
      was estimated using the TBARS (thio-barbituric acid reacting substances) method,
      in order to monitor membrane damage. Radiation-induced mortality of the animals
      following a lethal dose of gamma-radiation was also examined. KEY FINDINGS:
      Centella asiatica extract significantly reduced radiation-induced damage to DNA.
      The extent of radiation-induced mortality and lipid peroxidation was also found
      to be considerably reduced in animals administered with the extract. CONCLUSIONS:
      Centella asiatica rendered radioprotection to DNA and membranes against radiation
      exposure, both in vitro and in vivo. We have earlier reported that administration
      of the extract can prevent a radiation-induced decline in antioxidant enzyme
      levels. This suggests that radioprotection by Centella asiatica extract could be
      mediated by mechanisms that act in a synergistic manner, especially involving
      antioxidant activity.

PMID- 19589238
TI  - Characterization of the effect of penehyclidine hydrochloride on muscarinic
      receptor subtypes mediating the contraction of guinea-pig isolated
      gastrointestinal smooth muscle.
AB  - OBJECTIVES: The aim was to characterize the effect of penehyclidine
      hydrochloride, which mediates the relaxation of guinea-pig isolated
      gastrointestinal smooth muscle, on muscarinic receptor subtypes. METHODS:
      Radioimmune assay was used to determine cAMP levels in isolated guinea-pig
      gastrointestinal smooth muscle to compare the selective effects of penehyclidine
      hydrochloride on muscarinic receptor subtypes. KEY FINDINGS: The results
      indicated that the relaxing effect of penehyclidine hydrochloride on isolated
      gastrointestinal smooth muscle contraction induced by acetylcholine was stronger
      than that of atropine (based on PA2 values). In the radioimmune assay,
      penehyclidine hydrochloride increased the cAMP content in isolated guinea-pig
      stomach smooth muscle and decreased the cAMP content in isolated guinea-pig
      intestinal smooth muscle, but the difference was not statistically significant at
      a dose of 10 mumol/l. CONCLUSIONS: The results suggest that penehyclidine
      hydrochloride has little or no effect on M2 receptor subtypes in guinea-pig
      gastrointestinal smooth muscle.

PMID- 19589239
TI  - Monoketocholate can decrease transcellular permeation of methotrexate across Caco
      2 cell monolayers and reduce its intestinal absorption in rat.
AB  - OBJECTIVES: Bile salts have been shown to decrease the absorption of methotrexate
      in the rat intestine by an unknown mechanism. We aimed to examine this effect.
      METHODS: We assessed apical-to-basolateral (AP-BL) permeation of methotrexate (5
      muM) across Caco-2 cell monolayers pretreated with various concentrations (0,
      0.25, 0.5, 1, 3 and 5 mM) of sodium cholate or its semisynthetic analogue, sodium
      12-monoketocholate. We also determined the effect of orally administered 12
      monoketocholate on the intestinal absorption of methotrexate in rats to evaluate
      a possible in-vitro-in-vivo correlation. KEY FINDINGS: It was found that sodium
      cholate and sodium 12-monoketocholate decreased the AP-BL permeation of
      methotrexate at low concentrations (maximal inhibition at 0.25 and 1 mM,
      respectively) and increased it at higher concentrations. Determination of [(14)C]
      mannitol permeation and electrical resistance of monolayers during experiments
      showed that membrane integrity was not compromised at low concentrations of bile
      salts but was disrupted at higher concentrations. Subsequently, we examined the
      effect of the simultaneous oral administration of sodium 12-monoketocholate (4,
      20, 40 and 80 mg/kg) on the intestinal absorption of methotrexate in rats after
      an oral dose (5 mg/kg). The pharmacokinetic study showed that 12-monoketocholate
      at 4 and 20 mg/kg did not change the methotrexate area under the serum
      concentration-time curve whereas sodium 12-monoketocholate at 40 and 80 mg/kg
      significantly reduced it. CONCLUSIONS: Sodium 12-monoketocholate appears to
      decrease the intestinal absorption of methotrexate in rats by inhibition of
      transcellular active transport.

PMID- 19589240
TI  - Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L.
      and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated
      responses.
AB  - OBJECTIVES: The immunomodulatory effect of ginger, Zingiber officinale
      (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium
      aromaticum (Myrtaceae), essential oils were evaluated by studying humor- and cell
      mediated immune responses. METHODS: Essential oils were administered to mice
      (once a day, orally, for a week) previously immunized with sheep red blood cells
      (SRBCs). KEY FINDINGS: Clove essential oil increased the total white blood cell
      (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in
      mice. Moreover, it restored cellular and humoral immune responses in
      cyclophosphamide-immunosuppressed mice in a dose-dependent manner. Ginger
      essential oil recovered the humoral immune response in immunosuppressed mice.
      Contrary to the ginger essential oil response, sage essential oil did not show
      any immunomodulatory activity. CONCLUSIONS: Our findings establish that the
      immunostimulatory activity found in mice treated with clove essential oil is due
      to improvement in humor- and cell-mediated immune response mechanisms.

PMID- 19589241
TI  - Effects of losartan on fibrinolytic parameters and von Willebrand factor in
      Chinese subjects with hypertension: a comparative study versus atenolol.
AB  - To compare the effects of losartan and atenolol on plasma fibrinolytic parameters
      and von Willebrand factor (vWF), Chinese subjects with mild-to-moderate
      hypertension were randomized to receive losartan (50 mg/day; n = 30) or atenolol
      (50 mg/day; n = 30) for 8 weeks. If target blood pressure (< 140/90 mmHg) was not
      achieved at week 4, hydrochlorothiazide (12.5 mg/day) was also administered.
      Plasma levels of tissue plasminogen activator (tPA), plasminogen activator
      inhibitor-1 (PAI-1) and vWF were determined at baseline and after treatment.
      Between-group baseline characteristics and blood pressure decrease were
      comparable. Losartan significantly reduced plasma PAI-1 and vWF and PAI-1/tPA
      ratio. Atenolol significantly increased plasma tPA, but PAI-1, vWF and PAI-1/tPA
      ratio were unchanged. In conclusion, losartan, but not atenolol improved the
      fibrinolytic system and reduced plasma vWF levels in Chinese hypertensives.

PMID- 19589242
TI  - Simvastatin reduces OX40 and OX40 ligand expression in human peripheral blood
      mononuclear cells and in patients with atherosclerotic cerebral infarction.
AB  - This study investigated the effect of simvastatin on the expression of OX40 and
      OX40 ligand (OX40L) in vitro and in vivo. OX40 and OX40L mRNA and protein levels
      were measured in human peripheral blood mononuclear cells, using reverse
      transcription-polymerase chain reaction and Western blot, respectively, in
      response to simvastatin alone or given in combination with interferon-gamma,
      mevalonate or GW9662, a peroxisome proliferators-activated receptor-gamma (PPAR
      gamma) antagonist. Simvastatin induced down-regulation of OX40 and OX40L mRNA and
      protein in a concentration-dependent manner, and antagonized the interferon-gamma
      induced increase in OX40 and OX40L mRNA and protein levels. Mevalonate, but not
      GW9662, reversed the simvastatin-induced down-regulation of OX40 and OX40L
      expression, indicating that these effects were mediated through the mevalonate
      pathway. Serum levels of soluble OX40L and matrix metalloproteinase 9 levels were
      significantly reduced in patients with atherosclerotic cerebral infarction who
      were treated for 6 months with routine therapy plus simvastatin (n = 46) compared
      with patients receiving routine therapy alone (n = 30). These findings improve
      our understanding of the anti-inflammatory and immunomodulatory properties of
      simvastatin treatment for atherosclerotic disorders.

PMID- 19589243
TI  - Performance of the A-line Autoregressive Index (AAI) and of the Bispectral Index
      (BIS) at assessing depth of short-term sedation following cardiac surgery.
AB  - This study evaluated the correlation and agreement between the Bispectral Index
      (BIS) or A-line Autoregressive Index (AAI) and a clinical scoring system, the
      Ramsay Sedation Scale (RSS), in 40 patients after elective cardiac surgery and
      admission to the intensive care unit. All patients received sedation with
      propofol according to the study protocol. BIS, AAI and RSS were documented at two
      different levels of sedation: deep sedation RSS 4 - 6; and slight
      sedation/extubation RSS 2 - 3. Both the BIS and AAI agreed well with the RSS (eta
      coefficients of 0.902 and 0.836, respectively, for mean overall RSS stages). The
      systems agreed well among each other (overall intra-class correlations of 0.670
      for consistency and 0.676 for absolute agreement). There was significant
      discrimination between RSS 2 - 3 and RSS 4 - 6 with BIS and AAI (BIS mean
      difference of 24.73, 95% confidence intervals [CI] 21.08 - 28.37; AAI mean
      difference of 20.90, 95% CI 14.64 - 27.16). In conclusion, BIS and AAI correlated
      well with RSS overall and also at different levels of sedation.

PMID- 19589244
TI  - Subpopulations of stem-like cells in side population cells from the human bladder
      transitional cell cancer cell line T24.
AB  - Cancer stem cells can be isolated from human tumours using specific cell surface
      markers. Bladder cancer cells, however, lack specific cell surface markers,
      making this approach impracticable. In this study an alternative method was used,
      involving isolation of side population cells to explore the stem cell
      characteristics of bladder cancer. Side population cells were isolated from the
      bladder transitional cell cancer cell line T24 and examined for potential stem
      cell characteristics related to proliferation, cell cycle distribution, self
      renewal and differentiation. It was observed that T24 side population cells have
      stronger proliferative and colony formation abilities than non-side population
      cells. Side population cells were also more resistant to chemotherapy and
      radiotherapy, which may be due to expression of the ATP-binding cassette half
      transporter, sub-family G, member 2 protein. Overall, the results suggest that
      side population cells from the human bladder transitional cell cancer cell line
      T24 harbour stem-like cells.

PMID- 19589245
TI  - Polyphyllin D exerts potent anti-tumour effects on Lewis cancer cells under
      hypoxic conditions.
AB  - Paris polyphylla has been used to treat cancer in China for many years and
      components of the plant, such as polyphyllin D, may have potent antiproliferative
      effects in vitro. To investigate the potential antitumour effects of polyphyllin
      D on cancer cells under hypoxia, Lewis lung cancer cells and mouse tracheal
      epithelial cells were cultured with or without polyphyllin D under normoxic and
      hypoxic conditions. Proliferation and apoptosis of cells were assayed. Real-time
      reverse transcription-polymerase chain reaction was used to quantify the
      expression of hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF) mRNA. Polyphyllin D decreased cell
      proliferation, increased apoptosis and inhibited expression of HIF-1alpha and
      VEGF mRNAs in Lewis cells. These effects were greater under hypoxic than normoxic
      conditions. Polyphyllin D did not show a cytotoxic effect in non-tumour cells
      (mouse skin fibroblasts and tracheal epithelial cells). These results suggest
      that polyphyllin D potentially has anticancer effects in vitro under hypoxia.

PMID- 19589246
TI  - Significance of phosphatase and tensin homologue (PTEN), O(6)-methylguanine-DNA
      methyltransferase (MGMT), and DNA-dependent protein kinase catalytic subunit (DNA
      PKcs) protein expression in gynaecomastia.
AB  - This study was designed to investigate the pathogenesis of gynaecomastia by
      measuring phosphatase and tensin homologue (PTEN), O(6)-methylguanine-DNA
      methyltransferase (MGMT) and DNA-dependent protein kinase catalytic subunit (DNA
      PKcs) protein in breast tissue specimens from 68 patients with gynaecomastia and
      24 normal male controls using immunohistochemical staining. The gynaecomastia
      cases were divided into three different histological types: florid, intermediate
      and fibrous. The PTEN, MGMT and DNA-PKcs proteins were detected in both
      gynaecomastia and normal breast tissue, but the levels of immunohistochemical
      staining of each protein were significantly lower in gynaecomastia breast tissue
      than in normal breast tissue. There were also significant differences in the
      levels of immunohistochemical staining for the three proteins according to
      gynaecomastia histological type. These results suggest that abnormally low levels
      of PTEN, MGMT and DNA-PKcs protein in gynaecomastia breast tissue may play a role
      in the development of gynaecomastia. Further research is required to elucidate
      fully their individual roles in the pathophysiology of gynaecomastia.

PMID- 19589248
TI  - Clinical and experimental effectiveness of Astragali compound in the treatment of
      chronic viral hepatitis B.
AB  - Chinese herbs are widely used in the treatment of chronic viral hepatitis B. The
      effectiveness of 2 months' treatment with Astragali compound (AC), containing
      Radix Astragali and adjuvant components, was studied for the treatment of chronic
      viral hepatitis in 116 patients; 92 patients were given other drugs in regular
      clinical use for viral hepatitis (controls). The clinical efficacy of AC was
      significantly better in AC-treated patients than in controls. Negative
      seroconversions of hepatitis B virus (HBV) antigen e and HBV DNA were also
      significantly higher in AC-treated patients than in controls. Of eight duck viral
      hepatitis B models infected with duck hepatitis B virus (DHBV) and treated with
      AC, three showed negative seroconversion of DHBV DNA and serum DHBV DNA levels
      significantly decreased after AC administration compared with the controls; DHBV
      DNA was negative in biopsied liver tissue by in situ hybridization and
      immunohistochemistry in two ducks treated with AC. Pathological changes were
      milder in AC-treated ducks than in controls. These results indicate that AC may
      promote recovery from viral hepatitis and inhibit HBV replication.

PMID- 19589247
TI  - A new cell culture system for infection with hepatitis B virus that fuses HepG2
      cells with primary human hepatocytes.
AB  - Hepatitis B virus (HBV) infection exhibits a very narrow host range and shows a
      strong tropism for liver parenchymal cells, however none of the previously
      established experimental models can reproduce the natural process of HBV
      infection. In the present study, primary human hepatocytes were fused with HepG2
      cells to establish the hybrid HepCHLine-4 cell line with high susceptibility to
      HBV. The HepCHLine-4 cells expressed HBV-specific antigen when co-incubated with
      HBV-positive serum from a hepatitis B patient. Post-infection, HBV relaxed
      circular DNA and covalently closed circular DNA were detected in HepCHLine-4
      cells using a nested polymerase chain reaction, and HBV-specific particles were
      visualized by electron microscopy of the culture media of HepCHLine-4 cells.
      HepG2 cells were not susceptible to HBV infection under the same conditions. The
      HepCHLine-4 cells can be sub-cultured for > 12 months while maintaining
      susceptibility to HBV and may, therefore, be useful for studying HBV infection
      and the viral life cycle in human hepatocytes.

PMID- 19589249
TI  - Comparison of slime-producing coagulase-negative Staphylococcus colonization
      rates on vinyl and ceramic tile flooring materials.
AB  - This study investigated the colonization of slime-producing coagulase-negative
      Staphylococcus (CoNS) in 80 patient wards in Turkey (40 vinyl and 40 ceramic tile
      floors). A total of 480 samples that included 557 CoNS isolates were obtained.
      Slime production was investigated with the Christensen method and methicillin
      susceptibility was tested by the disk-diffusion method. There was a significant
      difference in the percentage of slime-producing CoNS isolates on vinyl (12.4%)
      versus ceramic tile flooring (4.4%). From vinyl flooring, the percentage of slime
      producing methicillin-resistant CoNS (MRCoNS) (8.9%) was significantly higher
      than for methicillin-sensitive CoNS (MSCoNS) (3.6%), whereas there was no
      difference from ceramic tile flooring (2.5% MRCoNS versus 1.8% MSCoNS). The most
      commonly isolated slime-producing CoNS species was S. epidermidis on both types
      of flooring. It is concluded that vinyl flooring seems to be a more suitable
      colonization surface for slime-producing CoNS than ceramic tile floors. Further
      studies are needed to investigate bacterial strains colonized on flooring
      materials, which are potential pathogens for nosocomial infections.

PMID- 19589250
TI  - Impaired fibrinolytic and blunted nitric oxide response to phlebotomy in
      cigarette smoking healthy blood donors.
AB  - This study was designed to investigate the effects of smoking on endothelial
      function in 88 healthy blood donors: 48 smokers and 40 non-smokers. Two markers
      of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) and nitric
      oxide (NO) levels, were measured at baseline and after phlebotomy. It has been
      proposed that phlebotomy acutely activates the renin-angiotensin-aldosterone
      system, thereby activating endothelial activity and increasing PAI-1 and NO
      expression. At baseline there were no significant differences between smokers and
      non-smokers in terms of PAI-1 expression and NO levels. After phlebotomy, both
      PAI-1 and NO levels were significantly increased in both groups. The increase in
      PAI-1 was more pronounced in smokers and the increase in NO was more pronounced
      in non-smokers. These findings suggest that smoking causes endothelial
      dysfunction, even in healthy smokers, which may remain silent until a clinically
      evident disorder develops.

PMID- 19589252
TI  - Use of cerebral state index monitoring to detect purposeful movement in unsedated
      brain-injured patients.
AB  - To test whether the cerebral state index (CSI) can be used as a measurement of
      the level of consciousness in unsedated brain-injured patients, 21 brain-injured
      adults were prospectively assessed in 77 separate sessions. After CSI monitoring
      was set up, the patient's motor responses to verbal and/or painful stimuli were
      assessed. CSI values were recorded before and after external stimulation.
      Purposeful movement in response to external stimuli was defined as command
      obeying and pain localization. Mean maximal CSI values increased significantly
      after external stimulation: from 71 to 89 and 49 to 62 in patients exhibiting
      purposeful and non-purposeful movements, respectively. The CSI value showed a
      high prediction probability (P(K) > 0.8) for detecting purposeful movement to
      external stimuli, especially after external stimulation (P(K) > 0.9). These
      results suggest that CSI monitoring might be a valid method for detecting
      purposeful movement in response to external stimuli in unsedated brain-injured
      patients.

PMID- 19589251
TI  - High-dose propofol triggers short-term neuroprotection and long-term
      neurodegeneration in primary neuronal cultures from rat embryos.
AB  - This study investigated the effects of propofol on primary neuronal cultures from
      rat embryos. Primary cortical neuronal cultures were prepared from Wistar rat
      embryos (E18). The viability of cells exposed to 0.01, 0.1 or 1 mg/ml propofol
      for up to 48 h was assessed using a methyltetrazolium assay. In order to evaluate
      the role of gamma-aminobutyric acid-A (GABA(A)) receptors, cells were also
      preincubated with the GABA(A)-receptor antagonists, gabazine and picrotoxin.
      Propofol at a concentration of 1 mg/ml significantly reduced cell viability after
      12 h. In contrast, this concentration led to a significant increase in cell
      viability at 3 and 6 h. The GABA(A)-receptor antagonists did not influence the
      neurodegenerative effect of propofol but abolished its neuroprotective effect.
      DNA fragmentation as a marker of apoptosis was elevated after 24 h propofol
      treatment. These results confirm that high doses of propofol can cause GABA(A)
      receptor triggered neuroprotection and a subsequent time-dependent, but GABA(A)
      independent, neurodegeneration in primary cortical neurons.

PMID- 19589253
TI  - Predicting the probability for fall incidence in stroke patients using the Berg
      Balance Scale.
AB  - This observational study investigated the relationship between balance, mobility
      and falls in 72 hemiplegic stroke inpatients, with the aim of developing a model
      for predicting fall risk. Fall history was recorded by interview, balance was
      assessed using the Berg Balance Scale (BBS) and activities of daily living were
      evaluated using the Functional Independence Measure (FIM). Variables differing
      between fallers and non-fallers were identified, and a stepwise regression
      analysis was performed to identify a combination of variables that effectively
      predicted fall status. Fallers (occasional and repeat; n = 27) had a shorter time
      from stroke onset, lower FIM scores on admission and discharge, lower BBS and
      Mini-Mental State Examination scores, a greater age and longer length of hospital
      stay compared with non-fallers (all differences were significant). A logistic
      model for predicting falls showed that BBS at admission was significantly related
      to falls, with fallers having lower BBS scores at admission (cut-off <or= 29;
      sensitivity 80%; specificity 78%). These data suggest BBS is a sensitive and
      specific measure for identifying stroke patients at risk of falling.

PMID- 19589254
TI  - Abnormal motor reflexes and dormant facial motor neurons in rats with facial
      facial anastomosis.
AB  - After facial nerve injury, some post-paralysis sequelae, such as synkinesis,
      hemispasm and 'crocodile tears' syndrome appear. The psychosocial impact of these
      sequelae is unavoidable. Despite recent advances and the growing popularity of
      this field, the pathophysiological mechanisms of facial nerve injury and
      regeneration are still not well understood. In this report, an abnormal motor
      reflex coincident with synkinetic facial movement was examined in a rat model
      using the blink reflex technique. Some dormant facial motor neurons were found
      which could not innervate through the suture site but remained alive. These
      results suggest that such dormant neurons might exert roles distinct from those
      of re-innervated neurons during facial nerve injury and regeneration. Further
      study is required to elucidate the biomolecular structure and
      electrophysiological features of such neurons.

PMID- 19589255
TI  - Unmet needs of patients with Parkinson's disease: interview survey of patients
      and caregivers.
AB  - We performed a 20-item questionnaire-based interview of 132 patients with
      Parkinson's disease (PD): 81 patients with Hoehn & Yahr (H&Y) stage I - III PD,
      and 51 caregivers of patients with H&Y stage IV - V PD, to evaluate patient and
      caregiver satisfaction with PD treatment. The survey revealed that PD patients
      often experience non-motor symptoms, which are not adequately alleviated by
      antiparkinsonian agents. Furthermore, PD patients want their physicians to listen
      to them and take their concerns seriously, to explain their disease
      comprehensively, and to provide the latest information on PD and its treatment.
      Both patients and caregivers agreed on anxiety toward the future, communication
      difficulties, and their different movement pace; however, there were differences
      in their relative perceptions of various aspects of daily care. The evaluation
      revealed that PD patients have unmet needs in their treatment and standards of
      care. Areas for future improvement as highlighted in this study include: the
      development of better treatment for motor symptoms, the development of new
      treatments for non-motor symptoms and improved two-way communication between
      patient and physician.

PMID- 19589256
TI  - The role of c-Jun N-terminal kinases 1/2 in transforming growth factor beta(1)
      induced expression of connective tissue growth factor and scar formation in the
      cornea.
AB  - Transforming growth factor beta(1) (TGF-beta(1)) plays an important role in
      corneal scar formation, mediated by connective tissue growth factor (CTGF). This
      study was designed to investigate the effect of c-Jun N-terminal kinase (JNK) 1
      and 2 on TGF-beta(1)-regulated CTGF gene expression and corneal scar formation in
      telomerase-immortalized human corneal stroma fibroblast (THSF) cells. The effects
      of CTGF, TGF-beta(1) and a JNK inhibitor (SP600125) on the proliferation of THSF
      cells were studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Both CTGF and TGF-beta(1) increased THSF cell proliferation
      and SP600125 inhibited this effect. Immunofluorescence analysis showed that TGF
      beta(1) stimulated the activation of JNK1/2 and induced cell migration, effects
      that were inhibited by SP600125. Analysis by real-time reverse transcription
      polymerase chain reaction showed that the mRNA levels of the genes for CTGF,
      fibronectin and collagen Ialpha(1) in wound and corneal scar formation were
      reduced by SP600125 pre-treatment.

PMID- 19589257
TI  - Ionic dissolution products of NovaBone promote osteoblastic proliferation via
      influences on the cell cycle.
AB  - This study investigated the effects of the ionic dissolution products of NovaBone
      on osteoblastic proliferation and cell cycle regulation. MG63 osteoblast-like
      cells were cultured in NovaBone-conditioned Dulbecco's Modified Eagle's Medium
      (DMEM) or control DMEM for 10 days. The concentration of silicon ions was
      significantly higher in NovaBone-conditioned DMEM than control DMEM. MG63 cells
      cultured in NovaBone -conditioned DMEM exhibited greater proliferation on days 1
      and 4 than control cells. There were increased proportions of Novabone
      conditioned DMEM-cultured cells in the S and G(2)/M phases, and decreased
      proportions in the G(0)/G(1) phase on days 1 and 4 versus control cells, while no
      differences were observed on days 7 and 10 between the two groups. Bone
      morphogenic protein 2 production increased in both groups, but was significantly
      higher for the NovaBone-conditioned DMEM-cultured cells on day 10 compared with
      the controls. In conclusion, the NovaBone ionic dissolution products,
      particularly the silicon ions, promoted proliferation of MG63 osteoblast-like
      cells in vitro via influences on the cell cycle.

PMID- 19589258
TI  - A comparison of two rehabilitation protocols after simultaneous bilateral total
      knee arthroplasty: a controlled, randomized study.
AB  - Post-operative outcomes after simultaneous bilateral total knee arthroplasty in
      115 patients randomly assigned to two rehabilitation protocols were compared. The
      traditional-protocol group performed a series of exercises on one leg and then
      repeated the same sequence on the other leg. The alternate-protocol group
      performed the same exercises, but alternated between legs with each individual
      repetition. Symptoms and function were assessed pre-operatively and at 1, 3, 6
      and 12 months post-operatively. The alternate-protocol group had lower visual
      analogue pain scale scores in the early post-operative period, as well as higher
      Knee Society Scores and SF-12 physical and mental health summary scores after 1
      and 3 months compared with the traditional-protocol group, but there were no
      differences between the two groups from 6 months post-operatively. There were no
      significant differences between the groups in terms of range of knee motion or
      incidence of deep vein thrombosis. The alternate-protocol for rehabilitation
      resulted in an early return to function and decreased pain levels following
      simultaneous bilateral total knee arthroplasty and was associated with the
      potential to produce more positive emotional states and earlier functional
      independence.

PMID- 19589259
TI  - Ghrelin and obestatin levels in end-stage renal disease.
AB  - Malnutrition is fairly common in end-stage renal disease (ESRD) patients,
      persistent lack of appetite being a major symptom. Ghrelin and obestatin are two
      hormones that are involved in appetite and energy homeostasis. The present study
      examined ghrelin and obestatin levels in 24 ESRD patients undergoing
      haemodialysis and 24 age-matched healthy controls. Serum and saliva ghrelin and
      obestatin levels in the ESRD patients were significantly higher compared with
      controls, while saliva ghrelin and obestatin levels in all study participants
      were significantly higher than serum levels. Saliva ghrelin correlated with serum
      ghrelin and saliva obestatin correlated with serum obestatin in all study
      participants, although there was no correlation between ghrelin and obestatin
      levels. In conclusion, the results suggest that the kidneys may have a role in
      the metabolism and/or clearance of obestatin, as they do for ghrelin. Further
      studies are needed to determine if elevated levels of these hormones in ESRD
      patients contribute to the malnutrition that is common in these patients.

PMID- 19589260
TI  - SHARP-2 gene silencing by lentiviral-based short hairpin RNA interference
      prolonged rat kidney transplant recipients' survival time.
AB  - Split- and hairy-related protein-2 (SHARP-2) controls the expression of
      interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), which both play a key role
      in transplant rejection. This study was designed to investigate whether SHARP-2
      short hairpin RNA interference (shRNAi) could prolong the survival of rat kidney
      transplant recipients. A lentiviral-based shRNAi construct, LV-SHARP-2iC, showed
      a SHARP-2 gene silencing efficiency of 84% in normal rat kidney cells. In
      activated T-cells, SHARP-2 gene silencing with the LV-SHARP-2iC construct
      resulted in 61% and 69% down-regulation of IL-2 and IFN-gamma, respectively,
      compared with a scramble control construct. When donor kidney was perfused with 5
      x 10(7) transforming units of the LV-SHARP-2iC construct, the median survival
      time of the transplant recipients was prolonged by 4 - 5 days compared with
      control groups. In conclusion, recombinant lentiviral LV-SHARP-2iC construct
      effectively silenced SHARP-2 gene expression, which reduced IL-2 and IFN-gamma
      mRNA expression and prolonged rat kidney transplant recipients' survival.

PMID- 19589261
TI  - Infrared thermography based on artificial intelligence as a screening method for
      carpal tunnel syndrome diagnosis.
AB  - This study further evaluated a computer-based infrared thermography (IRT) system,
      which employs artificial neural networks for the diagnosis of carpal tunnel
      syndrome (CTS) using a large database of 502 thermal images of the dorsal and
      palmar side of 132 healthy and 119 pathological hands. It confirmed the
      hypothesis that the dorsal side of the hand is of greater importance than the
      palmar side when diagnosing CTS thermographically. Using this method it was
      possible correctly to classify 72.2% of all hands (healthy and pathological)
      based on dorsal images and > 80% of hands when only severely affected and healthy
      hands were considered. Compared with the gold standard electromyographic
      diagnosis of CTS, IRT cannot be recommended as an adequate diagnostic tool when
      exact severity level diagnosis is required, however we conclude that IRT could be
      used as a screening tool for severe cases in populations with high ergonomic risk
      factors of CTS.

PMID- 19589262
TI  - Influence of borneol on in vitro corneal permeability and on in vivo and in vitro
      corneal toxicity.
AB  - This study examined whether borneol could enhance corneal drug permeability.
      Model drugs containing either synthetic or natural borneol were co-administered
      to isolated intact or de-epithelialized rabbit corneas and the apparent
      permeability coefficients were measured. Draize tests in rabbits and levels of
      isolated intact rabbit corneal hydration were used to measure in vivo and in
      vitro toxicity, respectively. Synthetic borneol (0.1%) increased corneal
      penetration of the lipophilic agents, indomethacin and dexamethasone, by 1.23 and
      2.40, respectively, and of the hydrophilic agents, ofloxacin, ribavirin and
      tobramycin, by 1.87, 2.80 and 3.89, respectively. For natural borneol, the
      corresponding fold increases were 1.67, 2.00, 2.15, 2.18 and 3.39, respectively.
      Removing the epithelium attenuated the penetration-enhancing effects of borneol.
      Borneol (0.1%) did not damage corneal tissue. The ability of borneol to enhance
      drug penetration through the outer corneal layer, particularly for highly
      hydrophilic drugs, suggests that further clinical investigation may be warranted.

PMID- 19589263
TI  - Sodium butyrate induces human colon carcinoma HT-29 cell apoptosis through a
      mitochondrial pathway.
AB  - Some tumours respond favourably to tumour necrosis factor-alpha (TNF-alpha).
      Despite this preferential sensitivity, resistance to TNF-alpha remains a clinical
      problem and more interest is now being focused on finding compounds that induce
      apoptosis through other pathways. Sodium butyrate (NaBt) has anti-tumour effects
      on colon cancer cells, inhibiting cell growth and promoting differentiation and
      apoptosis. In this study we investigated whether NaBt induced apoptosis in the
      human colon cancer cell line HT-29 and examined the intracellular mechanisms
      involved. Pre-incubation of cells with NaBt significantly increased apoptosis as
      measured by fluorescence activated cell sorter analysis and mitochondrial
      membrane potential determination. This effect could be blocked with the caspase
      inhibitors, z-VAD-fmk (pan-caspase inhibitor), z-DEVD-fmk (caspase-3 inhibitor)
      and z-LEHD-fmk (caspase-9 inhibitor), but not with z-IETD-fmk (caspase-8
      inhibitor). Enhancement of caspase-3 and caspase-9 activities suggests that NaBt
      induces apoptosis via mitochondrial pathways not involving TNF-alpha.

PMID- 19589265
TI  - Evaluation of risk factors in predicting coronary artery disease in patients with
      left bundle branch block.
AB  - This retrospective study examined whether classical risk factors for coronary
      artery disease (CAD) could also be used to predict CAD in patients with left
      bundle branch block (LBBB). Clinical and demographic features were studied in
      patients with/without CAD who presented with LBBB on their surface
      electrocardiograms and had undergone coronary angiography. Of the 312 patients
      with LBBB, 161 (51.6%) had CAD. Patients with CAD were more likely to be older,
      male, have CAD risk factors and to be taking acetylsalicylic acid or angiotensin
      converting enzyme inhibitors. A model with six independent variables (family
      history, smoking, angina, advanced age, hypertension and total cholesterol
      levels) was statistically significant in predicting CAD in patients with LBBB,
      with an ability to predict patients with and without CAD of 87.1% and 90.6%,
      respectively. Predictors of CAD in patients with LBBB are consistent with
      classical risk factors and may help the accurate prediction of patients with CAD.

PMID- 19589264
TI  - Multicentre, double-blind, randomized study of mitiglinide compared with
      nateglinide in type 2 diabetes mellitus patients in China.
AB  - This study investigated the non-inferiority of mitiglinide 10 - 20 mg versus
      nateglinide 120 mg, given orally three times daily for 20 weeks, in 291 Chinese
      type 2 diabetes mellitus (DM) patients in whom adequate blood glucose control had
      not been achieved by diet and exercise. Mitiglinide was started at 10 mg three
      times daily for 12 weeks and thereafter could be increased to 20 mg three times
      daily, depending on symptoms. In the mitiglinide and nateglinide groups the
      change in glycosylated haemoglobin (HbA(1c)) from baseline to week 12 was -0.53
      +/- 1.08% and -0.58 +/- 1.04%, respectively, and further decreased by -0.77 +/-
      1.06% and -0.71 +/- 1.12%, respectively, at week 20 compared with baseline. The
      intergroup difference (95% confidence interval) of HbA(1c) was 0.05% (-0.19,
      0.30) at week 12 and 0.06% (-0.31, 0.19) at week 20. Similar changes in HbA(1c)
      were seen in patients whose baseline value was < 8.0% as well as in those aged
      >or= 60 years. Comparable reductions in other blood glucose variables were noted
      in the two groups. Adverse events in the mitiglinide and nateglinide groups were
      noted in 54.5% and 57.9% of patients, respectively. In conclusion, mitiglinide 10
      - 20 mg three times daily provided similar blood glucose control to nateglinide
      120 mg three times daily in type 2 DM patients, including the elderly and
      patients with mild diabetes mellitus.

PMID- 19589267
TI  - Analysis of risk factors associated with outcomes in road traffic injury patients
      with acute lung injury.
AB  - Over 50% of road traffic injury (RTI) patients experience post-traumatic acute
      lung injury (ALI) and it is, therefore, extremely important to identify the risk
      factors related to the poor outcomes associated with ALI in RTI populations. This
      study evaluated 19 potential risk factors associated with the outcomes of ALI in
      366 RTI patients. They were divided into two groups: a 'favourable outcomes
      group' and an 'unfavourable outcomes group'. The results indicated that the Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score and the presence of
      gastrointestinal haemorrhage may help predict the outcomes of ALI in the early
      post-trauma phase of treatment. The duration of trauma and sepsis were shown to
      impact strongly on both the short- and long-term outcomes of ALI. Age (> 65
      years) and disseminated intravascular coagulation in the early RTI phase were
      also independent risk factors for a poorer short- and long-term outcome in ALI.

PMID- 19589266
TI  - Evaluation of lymphocyte subgroups in children with subacute sclerosing
      panencephalitis.
AB  - The aetiology of subacute sclerosing panencephalitis (SSPE) remains to be fully
      elucidated, although it follows infection with a hypermutant defective M-protein
      measles virus. This study analysed peripheral blood lymphocyte subgroups to
      determine their role in the pathophysiology of SSPE. It included 22 children with
      SSPE aged 2 - 15 years (patient group) and 22 age- and gender-matched healthy
      children (control group). In children < 6 years old, there were no statistically
      significant differences between the two groups in the proportions of lymphocytes
      expressing the surface markers CD3, CD8, CD19 or CD16/56, or in CD4/CD8 ratio.
      The proportion of CD4(+) lymphocytes in SSPE patients < 6 years of age was
      significantly lower compared with the control group. In children >or= 6 years
      old, there were no significant differences in the lymphocyte subgroups. In
      conclusion, these findings suggest that a low CD4(+) lymphocyte count might be
      responsible for SSPE in younger children.

PMID- 19589268
TI  - Characteristic genotypes of vascular endothelial growth factor are susceptible to
      ascites in patients with cirrhosis.
AB  - This study was designed to investigate whether different vascular endothelial
      growth factor (VEGF) genotypes are associated with ascites formation in cirrhotic
      patients. Seventy cirrhotic patients were included in the study: 25 cirrhotic
      patients with ascites and 45 cirrhotic patients without ascites. Patient
      characteristics were investigated and compared between the two groups. With
      regard to VEGF genotype, 42 patients were C/C and 28 patients were T/T or C/T.
      The genotypes T/T or C/T were observed in 23 cases (51%) among the non-ascites
      group, but in only five cases (20%) among the ascites group. Serum levels of
      albumin and creatinine, and the VEGF genotypes were significantly different
      between the two groups. Multiple regression analysis showed that serum levels of
      creatinine and the VEGF genotypes were significantly correlated with ascites
      formation. Thus, it can be concluded that VEGF genotyping might be a valuable
      susceptibility marker for ascites formation in cirrhotic patients.

PMID- 19589269
TI  - Advanced glycation end-products enhance calcification in vascular smooth muscle
      cells.
AB  - Advanced glycation end-products (AGEs), senescent macroprotein derivatives formed
      at an accelerated rate in diabetes, are closely associated with vascular
      calcification in humans. In this study, the hypothesis that AGEs enhance
      calcification in cultured vascular smooth muscle cells (VSMCs) was tested. Using
      real-time polymerase chain reaction (PCR) and specific protein assays, it was
      demonstrated that rat aortic VSMCs incubated with AGEs exhibited an increased
      expression of the AGE receptor (RAGE) and typical bone proteins, such as
      osteopontin and alkaline phosphatase. Incubation with AGEs also enhanced calcium
      accumulation in VSMCs in time- and dose-dependent manners. These AGEs-mediated
      changes in VSMCs were partially attenuated by a neutralizing antibody to RAGE.
      The results suggest that AGEs that accumulate in diabetes could elicit the
      osteoblastic differentiation of VSMCs, thereby contributing to vascular
      calcification via the RAGE pathway. Interruption of the AGE-RAGE interaction
      might be a promising target for therapeutic intervention to prevent diabetic
      vascular calcification.

PMID- 19589270
TI  - Effects of laparoscopically-assisted vaginal hysterectomy compared with abdominal
      hysterectomy on immune function.
AB  - This study evaluated the effects of laparoscopically assisted vaginal
      hysterectomy (LAVH) and abdominal hysterectomy (AH) on the immune system. Between
      May 2007 and July 2008, 84 women with uterine myoma were randomized in a double
      blind manner to undergo LAVH (n = 42) or AH (n = 42). Plasma levels of
      interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), C-reactive
      protein (CRP), T-lymphocyte CD3(+), CD4(+) and CD8(+) subpopulations, and natural
      killer (NK) cells were measured 24 h before and 24 h and 72 h after surgery. The
      IL-6, TNF-alpha and CRP levels in both groups increased significantly after
      surgery compared with pre-operative levels, and were significantly lower in the
      LAVH versus the AH group. Post-operative CD3(+) and CD8(+) T-cell counts in the
      AH group decreased significantly compared with pre-operative levels, whereas in
      the LAVH group they decreased but not to a statistically significant degree. Post
      operative CD4(+) T-cell counts in the AH group also decreased significantly at 24
      h after surgery, but were significantly increased at 72 h. In conclusion, LAVH
      does not significantly affect immune function compared with AH, suggesting the
      preservation of post-operative immunity, however further clinical studies are
      necessary.

PMID- 19589271
TI  - Myeloperoxidase (MPO) and interleukin-17 (IL-17) plasma levels are increased in
      patients with acute coronary syndromes.
AB  - There are several reports of myeloperoxidase (MPO) playing an important role in
      acute coronary syndromes (ACS). Interleukin-17 (IL-17) is a pro-inflammatory
      cytokine produced by activated CD4 T cells that has a chemotactic and activating
      effect on neutrophils. It has also been shown that IL-17 recruits neutrophils via
      the release of C-X-C chemokines. The roles of MPO and IL-17 in ACS, however, have
      not been established. This study measured plasma MPO and IL-17 levels in 10
      patients with ACS, 11 age- and sex-matched patients with stable angina and 12
      healthy control subjects. Plasma MPO and IL-17 levels were significantly elevated
      in ACS patients compared with the patients with stable angina and the healthy
      control subjects. In addition, plasma MPO levels correlated with plasma IL-17
      levels in all study participants. It is concluded that MPO and IL-17 are powerful
      indicators of acute coronary inflammation, however the data set was very small,
      so larger prospective studies are required.

PMID- 19589272
TI  - Comparison of the clinical and immunohistochemical features, including anaplastic
      lymphoma kinase (ALK) and p53, in inflammatory myofibroblastic tumours.
AB  - This retrospective study evaluated 15 cases of inflammatory myofibroblastic
      tumours (IMTs) to determine histological atypicality, clinicopathological
      features, outcomes, and expression of anaplastic lymphoma kinase-1 (ALK1) and
      p53, to assess potential pathological prognostic indicators. Nine patients with
      complete follow-up had no evidence of recurrence, including two with recurrent
      disease who were treated with additional surgery. Six patients had local
      recurrence and distant metastasis. Six (40.0%) tumours showed cellular
      atypicality. Significant correlations were found between histological atypicality
      and recurrence and metastasis. Recurrence was documented in 25.0% of ALK-positive
      and 63.6% ALK-negative IMTs, whereas metastasis was confined to the ALK-negative
      group. Recurrence and metastasis were documented in 50.0% and 25.0% of p53
      positive IMTs, respectively, and in 57.1% and 57.1%, respectively, of the p53
      negative IMTs. The IMT cases had high recurrence and metastasis and there were
      significant correlations between histological atypicality and recurrence and
      metastases, and between absence of ALK reactivity and recurrence. No correlation
      was found between p53 expression and any clinicopathological feature of IMT.

PMID- 19589273
TI  - Clinical value of tumour specific growth factor (TSGF) and carbohydrate antigen
      125 (CA-125) in carcinoma of the endometrium.
AB  - This study estimated the clinical value of tumour specific growth factor (TSGF)
      and carbohydrate antigen-125 (CA-125) in the diagnosis of endometrial carcinoma.
      Blood was collected from the peripheral and uterine veins of endometrial cancer
      patients, and serum TSGF and CA-125 levels were compared with those in uterine
      myoma patients (non-tumour controls) and normal women. Significantly higher
      levels of TSGF and TGSF-positive rates were observed in endometrial cancer
      patients versus non-tumour and normal controls. The sensitivity and specificity
      for detecting TGSF-positive rates in the endometrial carcinoma group were 64.9%
      and 62.5%, respectively. The TSGF levels in uterine blood were significantly
      higher than in peripheral blood and the TSGF-positive rate was also higher. The
      TSGF levels gradually increased with progression through the clinical stages and
      pathological grades of endometrial carcinoma. The sensitivity and specificity of
      combined TSGF and CA-125 for detecting endometrial cancer were 75.7% and 56.3%,
      respectively. It is concluded that there is an important correlation between
      serum levels of TSGF, CA-125 and endometrial cancer and that measurement of both
      TSGF and CA-125 combined would be of value in the diagnosis of endometrial
      carcinoma.

PMID- 19589274
TI  - On-pump coronary artery bypass surgery in high-risk patients aged over 65 years
      (EuroSCORE 6 or more): impact on early outcomes.
AB  - The results of on-pump coronary artery bypass graft (CABG) surgery in 166 high
      risk elderly patients (EuroSCORE 6 or more; over age 65 years [mean 71.8 years])
      were compared with 176 low-risk elderly patients (EuroSCORE below 6; over age 65
      years [mean 68.8 years]). There was no significant difference in hospital
      mortality or number of grafts between the two groups. Rates of inotropic agent
      use, intra-aortic balloon pump insertion and atrial fibrillation, and the
      duration of intensive care unit and hospital stay were significantly higher in
      high-risk than low-risk patients. There were no significant differences in the
      incidence of major complications between the two groups. The results suggest
      that, in selected patients, on-pump CABG can be safely performed in high-risk
      patients over 65 years old with no effect on mortality.

PMID- 19589276
TI  - Serious antimicrobial resistance status of pathogens causing hospital-acquired
      lower respiratory tract infections in North China.
AB  - Antimicrobial resistance patterns of pathogens causing hospital-acquired lower
      respiratory tract infections (LRTIs) in Shandong Province, China were
      investigated using data collected from January 2002 to December 2006. A total of
      10 337 isolates were characterized in sputum samples from 39 920 LRTI patients:
      68.72% were Gram-negative bacteria, 20.65% were Gram-positive bacteria, and
      10.62% were fungi. Organisms most frequently isolated were: Pseudomonas
      aeruginosa (16.88%), Klebsiella pneumoniae (10.80%), Escherichia coli (10.71%),
      fungi (10.62%), Staphylococcus aureus (9.68%) and Acinetobacter baumannii
      (9.03%). Imipenem was the most effective antibiotic against Gram-negative
      bacteria. Most Gram-positive bacteria were susceptible to vancomycin.
      Susceptibility to cephalosporins was not optimal and resistance to
      fluoroquinolones was high. Resistance of Gram-negative bacteria showed a rapid
      increase over the study period, while resistance of Gram-positive bacteria
      remained relatively stable. The emergence of resistance to commonly prescribed
      antimicrobial agents used against LRTI pathogens has compounded the problem of
      using empirical therapy and created selective pressure on physicians to use
      certain antibiotics.

PMID- 19589275
TI  - Antiproteinuric effect of angiotensin-converting enzyme inhibitors and an
      angiotensin II receptor blocker in patients with lupus nephritis.
AB  - Although the effects of angiotensin II receptor blockers (ARBs) on non-diabetic
      glomerulonephritis have been reported, studies of their effects on collagen
      vascular diseases, particularly lupus nephritis, are limited. In this
      retrospective, observational study, systemic lupus erythematosus (SLE) patients
      (n = 7) with lupus nephritis and uncontrolled proteinuria were treated with an
      angiotensin-converting enzyme inhibitor followed by the ARB losartan (25 - 50
      mg/day). Urinary protein excretion and renal function were evaluated. After 12
      months of losartan, mean urinary protein excretion decreased significantly by
      84.8%. Mean systolic and diastolic blood pressures also decreased significantly
      during the 12 months of losartan treatment, although not in normotensive
      patients. Complement 4, total complement activity and anti-dsDNA antibody levels,
      which are indices of SLE activity, and serum creatinine levels, which is an index
      of renal function, showed no change in response to losartan treatment. A more
      extensive evaluation of the effects of ARBs in patients with lupus nephritis and
      poorly controlled proteinuria is required.

PMID- 19589277
TI  - Unilateral transforaminal lumbar interbody fusion: a review of the technique,
      indications and graft materials.
AB  - Transforaminal lumbar interbody fusion (TLIF) is an alternative interbody fusion
      procedure in which interbody space is accessed via a path that runs through the
      far lateral portion of the vertebral foramen. TLIF reduces the potential
      complications of other approaches, including the transabdominal approach or
      posterior lumbar interbody fusion (PLIF), but still achieves clinical outcomes
      and circumferential fusion results comparable with PLIF. Operative indications
      for TLIF are contested among many spine experts. The optimal indications for
      using this technique are spondylolisthesis, degenerative disc disease with a
      specific discogenic pain pattern, lumbar stenosis with instability and recurrent
      lumbar disc herniation with radiculopathy. Various instrumentation techniques and
      graft materials are available to use in TLIF, and each option has benefits and
      disadvantages. Further research is needed, however, TLIF with one cage and
      excised local bone and augmented with a bilateral pedicle screw seems to be an
      effective and affordable treatment.

PMID- 19589278
TI  - The role of procalcitonin in gynaecological surgery.
AB  - We evaluated postoperative concentrations of inflammatory indicators, including
      procalcitonin, after gynaecological operations for benign and malignant tumours
      in patients with a normal postoperative course and assessed the utility of
      procalcitonin in differentiating between non-bacterial inflammation and
      bacteraemic complications in the postoperative period. This prospective study
      included 99 patients: 47 after a standard gynaecological operation (Piver I) and
      no postoperative infectious complications (group 1), 35 after a major procedure
      (Piver II or III) and no postoperative infectious complications (group 2), and
      five with postoperative sepsis after Piver II or III procedures (group 3). We
      also studied serum procalcitonin concentrations in a group of 12 patients (group
      4) with terminal forms of gynaecological cancer who were hospitalized for
      palliative treatment but did not undergo surgery. Postoperative C-reactive
      protein (CRP) concentration corresponded with extent of tissue trauma in groups 1
      and 2 and was significantly lower in group 1 than group 2. Inflammatory
      indicators were highest in groups 1 and 2 on postoperative day 2. In group 3, in
      which sepsis developed, values were highest on postoperative day 4. In
      particular, procalcitonin was > 2 ng/ml in all patients with postoperative sepsis
      by postoperative day 2 but was always <or= 2 ng/ml in patients without sepsis. In
      contrast, high procalcitonin levels were noted in the patients in group 4
      compared with group 3, with two-thirds of group 4 patients having levels > 2
      ng/ml, with no signs of infection or raised CRP. It is concluded that, for early
      detection of postoperative infectious complications after gynaecological surgery,
      procalcitonin levels > 2 ng/ml are more specific than CRP.

PMID- 19589279
TI  - Comparative analysis of protein expression in differentiated thyroid tumours: a
      multicentre study.
AB  - This study compared clinical features and protein expression profiles in
      differentiated thyroid tumours to identify protein markers with the potential for
      indicating malignancy status. Tissue microarrays were constructed using 119
      thyroid tumour samples (45 papillary carcinomas, 26 follicular carcinomas, 48
      adenomas). Generally, there was overexpression of proliferating cell nuclear
      antigen (PCNA), p53, matrix metalloproteinase (MMP)-7, Hector Battifora
      mesothelial-1 (HBME-1), MMP-2, pituitary tumour-transforming gene (PTTG) and
      human telomerase reverse transcriptase (hTERT) in malignant thyroid carcinomas,
      and overexpression of fragile histidine triad (FHIT), p16 and E-cadherin in
      thyroid adenomas. Multiple factor binary logistic regression analysis indicated
      that MMP-2, HBME-1, p16 and FHIT were independently related to differentiated
      thyroid tumours. Receiver-operating characteristics for these four factors showed
      HBME-1 as best for diagnostic accuracy. Sensitivity and specificity were enhanced
      using an HBME-1 and p16 cluster. HBME-1 expression was not significantly
      different for papillary and follicular carcinomas, whereas p16 expression was
      significantly specific.

PMID- 19589280
TI  - Attention deficit hyperactivity disorder in children: comparative efficacy of
      traditional Chinese medicine and methylphenidate.
AB  - Traditional Chinese medicine (TCM) is frequently used to treat attention deficit
      hyperactivity disorders (ADHD) in children in China. However, until now there has
      been no strong evidence to prove that TCM has better efficacy than western
      medicine. In this systematic study of 34 studies published in the Chinese
      literature, the effectiveness of TCM in treating ADHD in children was examined
      and compared with methylphenidate (MPH), which is widely used to treat ADHD. It
      was found that TCM may have equal or better effectiveness than MPH. However, the
      lack of high-quality clinical trials to support this conclusion means that it is
      not currently possible to recommend any particular kind of TCM preparation for
      treating ADHD in children.

PMID- 19589282
TI  - Rosette-forming glioneuronal tumour of the fourth ventricle with previous
      intratumoural haemorrhage: case report and review of the literature.
AB  - The case is reported of a rosette-forming glioneuronal tumour of the fourth
      ventricle (RGTFV) in a 27-year-old male. Symptoms included headache, severe
      vomiting and clumsy walking that had progressively worsened over 14 days.
      Computed tomography and magnetic resonance imaging indicated a 3.0 x 2.5 x 2.0 cm
      solid-cystic mass in the fourth ventricle and obstructive hydrocephalus. The
      tumour showed evidence of previous intra-tumour haemorrhage, with heterogeneous
      enhancement after contrast administration. Complete excision of the lesion was
      performed. Signs of previous intra-tumoural haemorrhage were seen intra
      operatively. The detailed clinical, radiological and pathological features in
      this patient are described and compared with existing literature on this type of
      tumour. Despite benign histological features and a reported favourable post
      operative course, there is still limited clinical experience with this type of
      tumour, however intratumoural haemorrhage may result in morbidity and mortality.
      This report will help provide better characterization of this entity, improving
      the diagnosis and potentially reducing mortality in RGTFV.

PMID- 19589281
TI  - The classification of posterior petrous meningiomas and its clinical
      significance.
AB  - This retrospective analysis of the clinical records of 42 patients was used to
      study the clinical significance of a classification system for posterior petrous
      meningiomas. According to clinical manifestations and radiological images,
      posterior petrous meningiomas were classified into three types: type I (cerebella
      type; 12 patients), tumours involved and compressed the cerebellum; type II
      (cranial nerve type; 16 patients), tumours involved the cranial nerves; and type
      III (combined type; 14 patients), tumours involved more than one structure such
      as the cerebellum, cranial nerves and the brain stem. All patients underwent
      microneurosurgery and the total resection rate was 90%. It was more difficult
      totally to resect type II and III tumours than type I tumours and the post
      operative functional outcomes were worse. Microneurosurgical techniques and
      skills are critical to increase the total resection rate of posterior petrous
      meningiomas in order to decrease the mortality and disability rates.

PMID- 19589283
TI  - Heterotopic pancreas within Meckel's diverticulum with obscure then massive
      gastrointestinal bleeding in a 12-year-old child: case report and review of the
      literature.
AB  - We report a case of a 12-year-old boy with heterotopic pancreas (HP) located in a
      Meckel's diverticulum (MD) and presenting as obscure gastrointestinal (GI)
      bleeding. Upper GI endoscopy and colonoscopy did not reveal the source of the
      bleeding, however, capsule endoscopy revealed a space-occupying lesion in the
      ileum. The patient developed massive bleeding and an emergency exploratory
      laparotomy was performed. A congested MD was discovered 100 cm from the
      ileocaecal valve using intra-operative endoscopy; the ulcerated tip of the
      diverticulum appeared to be the source of the bleeding. The MD and adjacent ileal
      segment were resected and an end-to-end anastomosis performed. Subsequent
      pathological examination revealed an ileal MD with HP tissue within the
      submucosa. The patient remains well, 12 months after the operation, with no
      evidence of recurrent bleeding. This case suggests that HP should be considered
      as one possible cause of obscure GI bleeding in children and capsule endoscopy is
      a valuable adjuvant tool in the diagnosis of HP in children.

PMID- 19589284
TI  - Fresh frozen plasma versus human albumin in paediatric craniofacial repair.

PMID- 19589285
TI  - Clinical and histological modifications in osteopetrotic bone: a review.
AB  - Osteopetrosis is one cause of diffuse osteosclerosis and bone fragility due to
      abnormal remodelling rate and balance. It may cause some serious skeletal
      abnormalities, with particular respect to long bones, and oral complications such
      as osteomyelitis and exposed necrotic bone. Orthopaedists and dentists should be
      aware of patients with the disease because of its effect on osteoclast function,
      which results in impaired wound healing. The purpose of this paper is to review
      the aetiology, pathogenesis and bone remodelling of osteopetrosis leading to some
      guidance for orthopaedic surgeons and dentists on the management of patients with
      osteopetrosis, with particular attention to fractures.

PMID- 19589286
TI  - Chlamydia pneumoniae and atherosclerosis: the role of mast cells.
AB  - Chlamydia pneumoniae (C. pneumoniae), a respiratory pathogen, has been implicated
      in the pathogenesis of atherosclerosis, an inflammatory progressive disease,
      characterized by the formation of atherosclerotic plaques. Among several types of
      inflammatory cells involved in the atherogenesis process, recently particular
      attention has been directed toward the mast cells. Experimental studies have
      provided several mechanisms by which C. pneumoniae and mast cells could play a
      role in all stages of atherosclerosis, from initial inflammatory lesions to
      plaque rupture. C. pneumoniae, as well as mast cells, may actively participate
      both through the production of cytokines and matrix-degrading metalloproteinases
      and by provoking apoptosis of atheroma-associated vascular cells, key events in
      plaque rupture. This mini-review provides a brief overview on adventitial
      inflammatory effects of C. pneumoniae and mast cells and their potential role in
      plaque instability. In addition, in this paper we review the role of mast cells
      in innate immunity.

PMID- 19589287
TI  - Radiosensitization effect of luteolin on human gastric cancer SGC-7901 cells.
AB  - The radiosensitizing effects of luteolin were studied in the gastric cancer cell
      line SGC-7901. SGC-7901 cells were treated with luteolin or/and irradiation, and
      radiosensitizing effects were assessed by colony-forming assay with cells and
      nude mice. In order to study the underlying mechanism, the levels of apoptosis
      related proteins, the activities of caspase-3 and -9, and the production of PGE2
      were measured. The results showed that luteolin could enhance irradiation-induced
      colonogenic inhibition and the activities of Caspase-3 and -9. The remarkable
      down-regulation of Bcl-2 and release of cytochrome C were also observed. In
      addition, significantly reduced production of PGE(2) was observed in luteolin
      plus radiation treatment by ELISA, as well as decreased expression levels of VEGF
      and HIF-1 alpha. Finally, luteolin significantly enhances the radioresponse of
      human tumors transplanted into nude mice. Our results indicate that luteolin may
      be a promising radiosensitizer for use in the treatment of gastric cancer.

PMID- 19589288
TI  - Nasal irrigation with lavonase as ancillary treatment of acute rhinosinusitis: a
      pilot study.
AB  - A wide variety of nasal irrigation systems are currently available for improving
      nasal symptoms, but few studies have compared their effectiveness with respect to
      patient age and type of nasal disease. This pilot study aims to compare the
      efficacy of two irrigation systems in 20 patients (12 males and 8 females; age
      range, 19-54 years; mean age, 36) with acute rhinosinusitis and treated only with
      antibiotic (levofloxacin 500 mg/day for 10 days) and topical nasal decongestant
      (naphazoline 2 puffs in each nostril twice daily for 7 days). Patients were
      randomly assigned to the treatments, using either a nasal syringe (10 mL saline
      solution, 3 times daily for 14 days) (Group 1) or the recently available Lavonase
      system (250 mL saline solution sac, twice daily for 14 days) (Group 2). Work-up
      included history, evaluation of signs and symptoms (nasal obstruction,
      rhinorrhea), nasal endoscopy, and anterior rhinomanometry. Nasal irrigation with
      the Lavonase system was found to be more effective in reducing symptoms, as all
      significantly diminished (p<0.05). In addition, the Lavonase system significantly
      decreased nasal resistances (p<0.05). This preliminary study shows that the
      ancillary treatment of acute rhinosinusitis with Lavonase may be useful.

PMID- 19589289
TI  - Occupational stress, job insecurity and perception of the health status in
      Italian teachers with stable or temporary employment.
AB  - The object of this study is to analyse job stress and insecurity and the
      perception of symptoms (health status) of 374 teachers (30 women and 74 men) with
      stable or temporary employment in schools in Pescara, a town in Central Italy.
      Job strain and job insecurity were analysed by an Italian version of the
      Karasek?s questionnaire, the perception of the health status by a 12 item test,
      and state and trait anxiety by STAI I and STAI II. There were no significant
      differences depending on the type of school. The young women with temporary
      contracts showed only higher levels of job insecurity than the women with stable
      employment, while those over 50 years old also showed more elevated values of job
      strain. Men with temporary contracts showed higher levels of both job insecurity
      and state and trait anxiety. The following highly significant correlations were
      observed: a) in women, job strain and perception of symptoms vs STAI I and STAI
      II (p<0.001); b) in men, job strain, job insecurity and perception of symptoms vs
      STAI II; job strain vs perception of symptoms as well as a negative correlation
      of decision latitude vs job insecurity, STAI I and STAI II (p<0.01). These
      results highlight differences in the perception of job insecurity between men and
      women. In particular, the decision latitude (skill decision + decision authority)
      plays an important role in men; temporary employment is mainly related to anxiety
      in men, while anxiety enhances the perception of poor health status mainly in
      women.

PMID- 19589290
TI  - Prevention of surgery in children with adenoidal hypertrophy treated with
      intranasal flunisolide: a 12-month follow-up.
AB  - Adenoidal hypertrophy (AH) represents one of the most frequent indications for
      surgery in children. Recently, treatment with intranasal corticosteroids has been
      suggested to decrease the size of AH. The aim of the study is to evaluate the
      long-term effect of intranasal flunisolide on AH during a 12-month follow-up. One
      hundred seventy-eight children with a grade III or IV AH at baseline endoscopic
      examination were enrolled in this randomised and controlled study. Children were
      treated with intranasal flunisolide or isotonic saline solution for 8 weeks.
      Subsequent assessment, including history and fiberoptic endoscopy, was made at 8
      weeks, and 6 and 12 months after treatment suspension. Flunisolide treatment was
      initially associated with significant (p<0.01) reduction of the degree of AH.
      However, during follow-up all but one of the non-allergic children relapsed,
      whereas most allergic children maintained AH size reduction (p<0.05). No
      clinically important adverse events were reported. In conclusion, this
      preliminary study demonstrates that an 8-week treatment with intranasal
      flunisolide is significantly associated with reduction of AH, however, the
      adenoidectomy avoidance was warranted only for allergic children.

PMID- 19589291
TI  - Management of tinnitus: oral treatment with melatonin and sulodexide.
AB  - The main problem arising from tinnitus is the disturbance it causes in day-to-day
      life and disturbance in sleep leading to fatigue and general discomfort. We
      attempted to study the effect of melatonin in conjunction with Sulodexide as a
      treatment method for tinnitus and evaluate its effectiveness. We studied 102
      patients suffering from tinnitus with a Prospective Randomised Controlled Study
      conducted in a tertiary care ENT department. After randomisation, 34 patients
      were treated with melatonin and Sulodexide, another 34 were treated with
      melatonin alone, and the remaining 34 (control group) were managed without
      therapy in order to evaluate spontaneous variations in quality of tinnitus.
      Patients were assessed prospectively with Tinnitus Handicap Inventory and
      Acufenometry both pre-treatment and post-treatment. Among the patients we
      studied, we found better results with both Tinnitus Handicap Inventory and
      Acufenometry in the group who received melatonin and Sulodexide as against
      melatonin alone. Any improvement was noted in the control group. In conclusion,
      our opinion is that melatonin in combination with Sulodexide is a viable
      treatment option for patients suffering from central or sensorineural tinnitus.

PMID- 19589292
TI  - Non-randomized pilot study on the evaluation of the quality of life and
      psychosocial stress before and after systemic therapy in patients affected by
      moderate to severe psoriasis.
AB  - Psoriasis has a major impact on patients? lives, affecting them physically,
      psychologically and socially. The aim of this study is to investigate psoriasis
      in relation to quality of life and psychological stress in two groups of patients
      treated with biologics and narrow-band UVB, respectively. We conducted a
      nonrandomized, prospective, comparative pilot study on 40 patients suffering from
      moderate to severe psoriasis. The comparison of the delta score of Skindex-29,
      Psoriasis Life Stress Inventory and the PASI at baseline and at the end of the
      treatment in the two groups highlighted the variation of the Psoriasis Life
      Stress Inventory which resulted significantly higher (P<0.001) in the group
      treated with biologics. The ease of administrating the combination Etanercept and
      Efalizumab, with consequent reduction of stress levels, attains a better control
      of psoriasis compared to phototherapy.

PMID- 19589294
TI  - Angina bullosa haemorrhagica: a case report.
AB  - Angina bullosa haemorrhagica (ABH) is a quite rare condition characterized by one
      or more blood blisters or bullae in the oropharynx. Here we report a case of ABH
      probably caused by a traumatic event in a diabetic patients. Diagnosis is based
      on clinical criteria and a prompt treatment alleviates the choking sensation and
      reduces secondary infections.

PMID- 19589293
TI  - Immune modulation by lactoferrin and curcumin in children with recurrent
      respiratory infections.
AB  - The clinical and immunologic effects of lactoferrin and curcumin (LC) oral
      supplementation were examined in healthy children with recurrent respiratory
      tract infections. Infections were reduced in children receiving LC. Immunologic
      analyses showed that LC supplementation resulted in a significant skewing of
      CD8+T lymphocytes maturation. Additionally: 1) CD14+, toll like receptor (TLR) 2
      expressing cells augmented (p= 0.005) whereas CD14+/TLR4+ diminished (p= 0.004);
      and 2) IL10 production by CD14+ cells was reduced in children receiving LC. LC
      supplementation results in immune modulation and could be clinically beneficial.

PMID- 19589295
TI  - Evaluation of symptoms and palatability in healthy volunteers after ingestion of
      an iced dessert by using different flavours.
AB  - It is well-known that digestion has a pivotal role in maintaining a state of
      wellbeing. The influence of certain foods and some herbal drugs has been
      ascertained. Epidemiological data show that the Mediterranean diet, with a high
      consumption of fresh vegetables and fruit, mainly citrus, has a beneficial effect
      and plays a protective gastrointestinal role. Previously, we assessed the
      influence on the eventual occurrence of symptoms during digestion of an iced
      dessert containing a mixture of digestive plant extracts, citrus juices and
      liquors, showing that its ingestion does not cause significant gastrointestinal
      symptoms in healthy volunteers. Taking into consideration that sensory properties
      of food may also influence digestion, we also evaluated the palatability of the
      product. In order to evaluate the effect of different tastes on the digestive
      processes, we performed a further similar evaluation with two new flavours. The
      ingestion of these iced desserts at the end of the meal does not cause
      significant gastrointestinal symptoms. Moreover, palatability median score shows
      a good appreciation of the products. Therefore, the combination of digestive
      herbs, citrus juice and liquors in different flavours gives rise to a product
      with a positive mix of good palatability, favourable acceptance and herbal
      constituents, able to maintain a good digestive condition.

PMID- 19589297
TI  - Impact of metabolic complications on antiretroviral treatment adherence: clinical
      and public health implications.
AB  - Antiretroviral therapy (ART) is an effective strategy for preventing disease
      progression of HIV infection, particularly when patients adhere closely to the
      treatment regimen. However, ART medications can cause side effects, including
      metabolic complications that can impact patients' adherence levels. Selected
      chronic complications associated with ART include lipodystrophy, hyperlipidemia,
      insulin resistance and diabetes, peripheral neuropathy, and bone disorders such
      as osteopenia/osteoporosis. In this article, we review the effects of these
      metabolic complications on ART adherence and approaches to prevent or reverse
      them.

PMID- 19589298
TI  - Dermatologic manifestations of HPV in HIV-infected individuals.
AB  - Dermatologic human papillomavirus (HPV) infection in HIV patients manifests as
      both anogenital and nongenital skin disease. Anogenital HPV-related disease
      includes benign condyloma acuminata, the most common cutaneous manifestation of
      genital HPV infection; intermediate malignancy or premalignant conditions
      including giant condyloma acuminata (also called Buschke-Loewenstein tumor), anal
      intraepithelial neoplasia, penile intraepithelial neoplasia, and vaginal or
      vulvar intraepithelial neoplasia; and frankly malignant disease including Bowen's
      disease and invasive anal, penile, or vulvar carcinoma. Cutaneous HPV-related
      disease in nongenital skin is also increased in HIV-positive patients, in the
      form of benign common warts, epidermodysplasia verruciformis-like skin lesions,
      and nonmelanoma skin cancers. This review and update addresses the above listed
      dermatologic manifestations of HPV disease in HIV-infected individuals, with an
      emphasis on new findings and published data from 2006 to 2008.

PMID- 19589299
TI  - Tuberculous meningitis in HIV-infected individuals.
AB  - HIV-infected individuals are at increased risk for all forms of extrapulmonary
      tuberculosis, including tuberculous meningitis. This risk is increased at more
      advanced levels of immunosuppression. The time interval between onset of symptoms
      and presentation to medical care may vary widely, and consequently individuals
      may present with acute or chronic meningitis. The clinical presentation of
      tuberculous meningitis in HIV-infected individuals is more likely to include an
      altered level of consciousness, cranial imaging is more likely to show cerebral
      infarctions, and the yield of culture of cerebrospinal fluid may also be greater.
      Given that delayed initiation of therapy is a strong predictor of mortality in
      cases of tuberculous meningitis, clinicians must consider tuberculosis in the
      differential diagnosis of the HIV-infected individual with acute or chronic
      lymphocytic meningitis. Additional treatment considerations for HIV-infected
      individuals include the timing of initiation of antiretroviral therapy, the
      potential for drug-drug interactions, and the role of adjunctive corticosteroid
      therapy.

PMID- 19589300
TI  - HIV-related neurocognitive impairment in the HAART era.
AB  - Neurocognitive impairment is common in people living with HIV and AIDS. Prior to
      highly active antiretroviral therapy (HAART), cognitive impairment primarily
      affected patients with advanced disease, and was a more rapidly progressive
      illness. With the use of HAART, cognitive impairment improved, along with the
      overall health of HIV-positive patients. However, it is still a prevalent
      problem, even in patients with desirable CD4+ count and undetectable plasma viral
      load. In this review, we address the nature of HIV-related neurocognitive
      impairment in the HAART era, including its etiology, pathology, appropriate
      diagnostic tools for clinical practice and research, and rational treatment
      approaches.

PMID- 19589301
TI  - Internal medicine/primary care reminder: what are the standards of care for HIV
      positive patients aged 50 years and older?
AB  - The demographics of HIV-positive persons in the United States signal a steady
      shift toward an older population. The relationship between aging and HIV
      infection suggests that there is an additive and possibly synergistic effect
      increasing the risk for numerous common medical conditions, including heart
      disease, cancer, osteoporosis, frailty, depression, and dementia. Given the
      current crisis in the US health care system regarding universal access to quality
      primary and geriatric care, the aging of the HIV-positive population will pose
      numerous challenges to providers and policy makers. This review summarizes key
      areas of knowledge and concern regarding the care of HIV-positive persons aged 50
      years and older.

PMID- 19589302
TI  - Management of patients with the immune reconstitution inflammatory syndrome.
AB  - A significant proportion of patients present with the immune reconstitution
      inflammatory syndrome (IRIS) after commencing antiretroviral therapy (ART). This
      syndrome is most frequently associated with infective causes. The lack of
      evidence-based treatment guidelines poses challenges in the management of these
      patients. Alternative causes for deterioration should be excluded, and
      optimization of treatment for the underlying opportunistic infection is
      essential. In addition, anti-inflammatory or immunomodulatory therapy may be
      considered, particularly in severe cases. Corticosteroids, the only treatment for
      which clinical trial data exist (for treating paradoxical tuberculosis-associated
      IRIS), are the treatment most frequently used in IRIS. Limited anecdotal reports
      of benefit exist for other agents, including NSAIDs, pentoxifylline, montelukast,
      thalidomide, and hydroxychloroquine. Therapeutic procedures (eg, aspiration of
      pus collections) play an important role in some patients. Interruption of ART may
      be considered in life-threatening forms of IRIS.

PMID- 19589303
TI  - Prospective controlled trial of STAR total ankle replacement versus ankle fusion:
      initial results.
AB  - BACKGROUND: Mobile-bearing ankle replacements have become popular outside of the
      United States over the past two decades. The goal of the present study was to
      perform a prospective evaluation of the safety and efficacy of a mobile-bearing
      prosthesis to treat end stage ankle arthritis. We report the results of three
      separate cohorts of patients: a group of Scandanavian Total Ankle Replacement
      (STAR) patients and a control group of ankle fusion patients (the Pivotal Study
      Groups) and another group of STAR total ankle patients (Continued Access Group)
      whose surgery was performed following the completion of enrollment in the Pivotal
      Study. MATERIALS AND METHODS: The Pivotal Study design was a non-inferiority
      study using ankle fusion as the control. A non-randomized multi-centered design
      with concurrent fusion controls was used. We report the initial perioperative
      findings up to 24 months following surgery. For an individual patient to be
      considered an overall success, all of the following criteria needed to be met: a)
      a 40-point improvement in total Buechel-Pappas ankle score, b) no device
      failures, revisions, or removals, c) radiographic success, and d) no major
      complications. In the Pivotal Study (9/00 to 12/01), 158 ankle replacement and 66
      arthrodesis procedures were performed; in the Continued Access Study (4/02 to
      10/06), 448 ankle replacements were performed, of which 416 were at minimum 24
      months post-surgery at time of the database closure. RESULTS: Major complications
      and need for secondary surgical intervention were more common in the Pivotal
      Study arthroplasty group than the Pivotal Study ankle fusion group. In the
      Continued Access Group, secondary procedures performed on these arthroplasty
      patients decreased by half when compared with the Pivotal Arthroplasty Group.
      When the Pivotal Groups were compared, treatment efficacy was higher for the
      ankle replacement group due to improvement in functional scores. Pain relief was
      equivalent between fusion and replacement patients. The hypothesis of non
      inferiority of ankle replacement was met for overall patient success. CONCLUSION:
      By 24 months, ankles treated with STAR ankle replacement (in both the Pivotal and
      Continued Access Groups) had better function and equivalent pain relief as ankles
      treated with fusion.

PMID- 19589304
TI  - Recombinant bone morphogenetic protein-2 (rhBMP-2) in high-risk ankle and
      hindfoot fusions.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of rhBMP-2 on
      bone healing in patients who undergo high-risk ankle & hindfoot fusions.
      MATERIALS & METHODS: Patients who underwent high-risk, elective ankle and
      hindfoot fusions treated with rhBMP-2 augmentation were reviewed for clinical
      outcomes and complications. A total of 112 fusion sites (69 patients) were
      reviewed for analysis. The mean age of the patients was 52 years (range, 21 to 84
      years). There were 37 males (53%) and 32 females (47%). Forty-four patients (64%)
      were smokers and 13 patients (19%) were diabetic. A history of high-energy trauma
      was present in 47 (68%) patients and avascular necrosis of the talus was present
      in 22 patients (32%). Forty-five patients (65%) had multiple risk-factors. The
      exclusion criteria were peripheral vascular disease, infection, and patients who
      were not available for the usual follow-up protocol. Internal and/or external
      fixation was utilized for ankle and hindfoot fusions. Bone graft was used only
      for patients who had defects or malalignment. Postoperatively, nonweightbearing
      radiographs were taken every 2 to 4 weeks (3 views per site). When plain
      radiographic union was evident, a confirmatory CT scan was obtained. RESULTS:
      Overall, 108 fusion sites went on to union (96% union rate) at a mean time of 11
      weeks (as assessed by a CT scan) [ankle joint at 10 weeks; subtalar joint at 12.3
      weeks; talonavicular joint at 12.7 weeks and calcaneocuboid joint at 10.9 weeks].
      Different union times between ankle, subtalar, talonavicular, and calcaneocuboid
      joint were not significant (p = 0.2571, Kruskal-Wallis Test Nonparametric ANOVA).
      All sites: [No graft] vs. [Autograft] vs. [Allograft]: p = 0.2421 (Kruskal-Wallis
      Test Nonparametric ANOVA), were not statistically significant. Complications
      included nonunion in 5 of 112 joints in 3 patients (4% joint nonunion rate; 4%
      patient nonunion rate) [subtalar joint, n = 2; talonavicular joint, n = 1; and
      calcaneocuboid joint, n = 1]. Two patients had wound complications and one other
      patient had a deep infection; all were successfully treated with local wound
      care, negative-pressure dressings and antibiotics. CONCLUSION: We believe rhBMP-2
      is an effective adjunct for bone healing in patients who undergo high-risk ankle
      and hindfoot fusions. Low complication rates were observed in this study.

PMID- 19589305
TI  - Correlation of Harris mats, physical exam, pictures, and radiographic
      measurements in adult flatfoot deformity.
AB  - INTRODUCTION: In many reports describing flatfoot deformities, the abnormality is
      described using observations from physical examination, radiographs, or foot
      imprints. Correlation of these measurements is often lacking, making
      determination of the magnitude of the deformity or its surgical correction
      difficult to quantify. MATERIAL AND METHODS: Weightbearing AP and lateral
      radiographs were obtained on 25 patients (39 feet) with a clinically apparent
      flatfoot deformity and an asymptomatic control group of 28 subjects (56 feet).
      Radiographs were examined for the lateral talometatarsal angle, the lateral
      talocalcaneal angle, calcaneal pitch, first metatarsocuneiform height, medial
      cuneiform -fifth metatarsal height, metatarsus primus elevatus, plantar gapping
      at the first metatarsocuneiform joint, the AP talonavicular coverage angle, and
      the metatarsus adductus angle. Harris mat imprints were obtained on each foot and
      measured for the magnitude of the flatfoot deformity. Physical examination
      included the subjective appearance to the examiner of the degree of pes planus
      (none, mild, moderate, severe), hindfoot valgus, and ankle range of motion.
      Photographs of the hindfoot were obtained in a standardized manner, and hindfoot
      valgus was measured from these photos and compared to the measured hindfoot
      valgus on the physical exam. RESULTS: Statistically significant differences
      between the two groups were found in the lateral talometatarsal angle, lateral
      talocalcaneal angle, calcaneal pitch, first metatarsocuneiform height, the AP
      talonavicular coverage angle, Harris mat imprint score, subjective pes planus
      score, hindfoot valgus measurement from both photographs and physical
      examination, ankle range of motion (all with a p value less than 0.01), and the
      metatarsus adductus angle (p = 0.019). No patient in the control group and 14
      (36%) in the flatfoot group had evidence of plantar gapping at the first
      metatarsocuneiform joint. In the flatfoot group, statistically significant
      correlations were demonstrated between the Harris mat score and heel valgus as
      measured by photographic and physical examination, subjective pes planus grading
      by physical exam, the lateral talometatarsal angle, and the first
      metatarsocuneiform height. CONCLUSION: This study validates the use of the Harris
      mat imprint as an effective method of quantifying the magnitude of a flatfoot
      deformity. We also found a statistically significant decrease in ankle range of
      motion in the flatfoot group, indicating that tightness of the gastrocsoleus
      complex is part of the pathophysiology of flatfoot deformity.

PMID- 19589307
TI  - Improvement in surgical consent with a preoperative multimedia patient education
      tool: a pilot study.
AB  - BACKGROUND: Preoperative education and discussion is a crucial part of the
      surgeon-patient relationship. The purpose of this study was to assess the
      efficacy of a multimedia education tool to improve patients' understanding when
      used as an adjunct to the usual verbal consent process regarding first
      metatarsophalangeal joint (MTPJ) arthrodesis surgery. MATERIALS AND METHODS:
      Thirty-one patients were prospectively recruited. There were 24 female and seven
      male patients with an average age of 56 years. Well-rehearsed, standardized and
      thorough information regarding the surgery, its risks, benefits, and usual post
      operative course were supplied verbally to each patient. Patient understanding
      was then assessed with a condition specific questionnaire. Following this, each
      completed a multimedia educational program and repeated the questionnaire,
      including supplementary questions regarding ease of understanding and
      satisfaction with the two methods. RESULTS: The patients answered 62% questions
      correctly before the multimedia presentation compared to 87% after it (p <
      0.001). Patients rated the ease of understanding of the multimedia module as a
      median 9.3 cm along a 10-cm visual analogue scale and 9.1 cm when asked whether
      it contained the appropriate amount of information to make a decision about
      surgery. Ninety percent of patients considered that the multimedia tool answered
      their questions about surgery as well or better than the treating surgeon.
      CONCLUSION: This study demonstrated that incorporation of a computer-based,
      multimedia education tool into to the surgical consent process improved patient
      understanding of the risks, benefits and usual postoperative course following
      first MTPJ arthrodesis surgery.

PMID- 19589306
TI  - Hindfoot motion following reconstruction for posterior tibial tendon dysfunction.
AB  - INTRODUCTION: Due to advances in technology, segmental gait analysis of the foot
      is now possible and can elucidate hindfoot deformity in persons with posterior
      tibial tendon dysfunction (PTTD). This study evaluated the motion of the hindfoot
      and ankle power following surgical reconstruction for PTTD utilizing a segmental
      foot model during gait. MATERIALS AND METHODS: Twenty patients who underwent
      posterior tibial tendon reconstruction for Stage 2 PTTD using transfer of the
      flexor digitorum longus tendon to the navicular tuberosity, reconstruction of the
      calcaneo-navicular ligament complex, and a medial displacement calcaneal
      osteotomy were evaluated at a minimum followup of 1 year. Three-dimensional gait
      analysis was performed utilizing a 4-segment foot model. Temporal-spatial
      parameters included walking velocity, cadence, step length, and single support
      time. Sagittal, coronal, and transverse hindfoot motion with respect to the
      tibia/fibula and ankle power was calculated throughout the gait cycle. RESULTS:
      Walking velocity, cadence, and step length were not significantly different
      between the study subjects and the normal control group. Study patients did show
      a significantly smaller single support time on both the affected and unaffected
      limbs compared to controls. There was no statistical difference in plantarflexion
      dorsiflexion, varus-valgus, or ankle push-off power between the affected and
      unaffected sides of the study subjects, or between the affected side and the
      controls. CONCLUSION: In this preliminary postoperative study, surgical
      reconstruction for PTTD effects quantifiable objective improvement in walking
      velocity, hindfoot motion and power.

PMID- 19589308
TI  - Evaluation of the hallux morbidity of single-incision flexor hallucis longus
      tendon transfer.
AB  - BACKGROUND: Achilles tendinosis and chronic Achilles tendon ruptures are
      relatively frequently encountered by orthopaedic surgeons. One treatment for
      patients who fail to respond to conservative management involves augmentation of
      the repair with transfer of the flexor hallucis longus (FHL), using either a
      single-incision or double-incision technique. Despite the frequency of this
      procedure, little is known about the associated donor morbidity. We report the
      effects of the single-incision technique on hallux function. MATERIALS AND
      METHODS: We retrospectively reviewed 48 patients who underwent a single-incision
      FHL tendon transfer for chronic Achilles tendon rupture or Achilles tendinosis.
      Twenty-two patients (mean followup, 28 months) completed the study. The average
      age was 56 years. Outcome measures included the American Orthopaedic Foot and
      Ankle Society (AOFAS) hallux metatarsophalangeal (MTP) joint and interphalangeal
      (IP) joint scores, the Health Related Quality of Life Measures Short Form (SF
      36). Also, the average of two pedobarographic measurements of both feet and
      strength testing of the FHL of both feet were recorded. RESULTS: Decreased distal
      phalangeal pressure and FHL weakness were demonstrated (p < 0.05). No difference
      was noted in plantar pressure of the first or second metatarsal head. The high
      score on the AOFAS hallux MTP-IP scale demonstrated improved patient forefoot
      function after FHL transfer through a single-incision technique. CONCLUSION:
      Flexor hallucis longus tendon transfer using a single-incision technique results
      in decreased flexion power at the IP joint as demonstrated by decreased distal
      phalangeal pulp pressure; however, this appears to be a laboratory finding as
      patient function remains high.

PMID- 19589309
TI  - Anterior double plating for rigid fixation of isolated tibiotalar arthrodesis.
AB  - BACKGROUND: Arthrodesis is the most common procedure used to treat end-stage
      osteoarthritis of the ankle, particularly in patients with difficult conditions
      such as poor bone quality. While many techniques are available to fuse the ankle,
      current recommendations favor the use of internal fixation with screws and/or
      plates. Despite of progress, the complication rate remains a major concern. Non
      union is one difficult problem especially with difficult bone conditions,
      particularly the loss of bone stock on the talar side. Therefore, fusion of the
      tibiotalar joint is often extended to the talocalcaneal joint to provide
      sufficient stability. To preserve the subtalar joint, an anterior double plate
      system for rigid fixation of isolated tibiotalar arthrodesis was developed. This
      is a preliminary report on the clinical and radiological outcome with this
      technique. MATERIALS AND METHODS: Twenty-nine patients (15 men, 14 women; one
      ankle per patient) were treated from October 2006 to September 2007. We converted
      16 ankles with osteoarthritis and difficult bone conditions, four non-united
      ankle arthrodeses, and nine failed total ankle replacements to an isolated
      tibiotalar arthrodesis using anterior double plating. If necessary, we used solid
      allograft to fill bony defects. Outcomes included bone union as assessed by
      radiographs, pain as indicated by the American Orthopaedic Foot and Ankle Society
      scores, and patient satisfaction. RESULTS: Solid arthrodesis was achieved after
      an average of 12.3 (eight to 26) weeks in the 16 ankles without bone graft
      interposed between the tibia and talus, and 14.3 (range, 8 to 26) weeks in the 13
      ankles with interpositional bone allograft. Radiographs showed that the position
      of arthrodesis obtained at the time of surgery did not change in any patient up
      to one year after surgery. The mean American Orthopaedic Foot and Ankle Society
      (AOFAS) Hindfoot Score increased from 37 (range, 20 to 63) preoperatively to 68
      (range, 50 to 92) at the last followup. Twenty-seven patients (93%) were
      satisfied with their outcome and indicated they would have the operation again.
      No complications were noted. CONCLUSION: The anterior double plating system was
      shown be a reliable method to achieve solid isolated tibiotalar arthrodesis, even
      in ankles with difficult conditions such as loss of bone stock due to failed
      total ankle arthroplasty.

PMID- 19589310
TI  - Total sesamoidectomy for painful hallux rigidus: a medium-term outcome study.
AB  - BACKGROUND: The nature of the sesamoid complex in the development of hallux
      rigidus or limitus (HL) has been poorly characterized and the role of the
      sesamoids in the surgical management of this condition has not been explored.
      Previous surgical approaches in younger active patients unsuited to destructive
      procedures have been limited. MATERIALS AND METHODS: Thirty-three patients (36
      procedures) were reviewed between 2 and 4 years following total sesamoidectomy
      for the management of hallux rigidus/limitus. The American Orthopedic Foot &
      Ankle Society hallux (AOFAS) clinical rating system was used to compare pre and
      postoperative scores. The range and quality of motion and transfer metatarsalgia
      were noted. The three most important patient problems and the degree to which
      these had been addressed by the surgery and the time to maximal improvement were
      noted. RESULTS: No significant functional impairment or malalignment were found.
      There were no instances of pain on metatarsal compression, or of transfer
      metatarsalgia with or without callus formation. A highly statistically
      significant improvement in AOFAS scores was found (p < 0.001). CONCLUSION: High
      levels of clinical improvement and patient satisfaction were found following
      total sesamoidectomy. No deleterious consequences of sesamoid removal were
      observed. For symptomatic patients where a joint replacement/fusion is not
      indicated, total sesamoidectomy was beneficial as an interim procedure, for
      joints with a moderate (grades 2 to 3) degree of arthrosis.

PMID- 19589311
TI  - Progressive neuromuscular planovalgus foot deformity treated with a modified
      extra-articular subtalar fusion.
AB  - BACKGROUND: Obtaining a successful subtalar fusion in the pediatric population
      can be challenging. We present our results with a modified extraarticular method.
      MATERIALS AND METHODS: - We retrospectively evaluated 12 patients (17 feet) with
      progressive neuromuscular planovalgus foot deformity that underwent an extra
      articular subtalar arthrodesis with the combined Batchelor-Grice procedure. All
      patients were ambulatory and were treated conservatively with braces prior to the
      operation. The average followup was 10 (range, 5 to 17) years. Postoperatively
      the feet were immobilized in short leg casts for 6 weeks. Preoperative and
      postoperative appearance of the feet, the clinical symptoms and radiographic
      measurements were recorded. RESULTS: Sustained correction and solid fusion took
      place in all feet. Foot appearance and gait pattern of the patients were
      improved, while preoperative complaints were reduced. Radiographic healing was
      noted in all cases. CONCLUSION: This technique is an effective treatment for the
      correction of the deformity as it gives a greater assurance of solidarity than
      when either of the two procedures is used alone.

PMID- 19589312
TI  - Results of metallic Hemi-Great Toe Implant for Grade III and early Grade IV
      hallux rigidus.
AB  - INTRODUCTION: The authors the short-term and mid-term results of patients with
      their preoperative status who were surgically treated for advanced Grade III and
      early Grade IV symptomatic hallux rigidus using the Futura Hemi-Great Toe
      Implant. MATERIALS AND METHODS: The authors were able to contact 23 of 33
      consecutive patients. They had a detailed evaluation preoperatively and came in
      for a detailed mid-term evaluation. Some of the patients were able to come in
      routinely for detailed periodic evaluations. RESULTS: Periodic evaluations showed
      most patients had a gradual improvement of function over the first 2 years.
      Patients with early Grade IV disease had a greater propensity to develop early
      recurrence of their dorsal osteophyte at or before their mid-term followup
      (average 6 years). In this group of patients, the Futura Hemi-Great Toe Implants
      lead to 88% good to excellent mid-term results and 88% patient satisfaction over
      a 6-year average followup. CONCLUSION: Patients with early Grade IV hallux
      rigidus tend to develop progressive sesamoid arthritis and recurrent dorsal
      osteophyte formation more rapidly than advanced Grade III patients.

PMID- 19589313
TI  - Glucocorticoid injections in lesions of the achilles tendon.
AB  - BACKGROUND: A number of non-operative interventions are used to manage Achilles
      tendinopathy. In particular, local glucocorticoid injections have generated
      controversy. Although a number of case reports indicate symptomatic relief
      following glucocorticoid injection, one systematic review found little evidence
      to support their efficacy. Furthermore, local glucocorticoid injections may be
      associated with rupture of the Achilles tendon. This systematic review considered
      all available clinical trials measuring the effect of local glucocorticoid
      injections on symptom relief in patients with Achilles tendinopathy. MATERIALS
      AND METHODS: The search strategy encompassed five databases: Medline, EMBASE,
      CINAHL, AMED and the Cochrane Library. Only studies reporting the outcome of
      glucocorticoid injection for Achilles tendinopathy were included. RESULTS: A
      total of 72 articles were identified, five of which met the inclusion criteria.
      These included one randomized controlled trial, three retrospective studies, and
      one prospective case series. CONCLUSION: There is no consensus as to whether
      local glucocorticoid injections have a therapeutic role in the treatment of
      Achilles tendinopathy However, they may incur a risk of tendon damage and
      therefore further research is required before glucocorticoid injections can be
      recommended for use in Achilles tendinopathy.

PMID- 19589314
TI  - Early mobilization of operatively fixed ankle fractures: a systematic review.
AB  - BACKGROUND: It is commonly believed that early motion after joint fixation is
      advantageous, especially in the upper limb. In the ankle joint this is much less
      clear. No previous systematic review of the evidence for this could be found in
      the literature. MATERIALS AND METHODS: Nine randomized control trials were
      identified which met the inclusion criteria and compared early motion of the
      ankle joint to immobilization in a cast for 6 weeks. These varied in quality and
      numbers. All treated patients equally in all other respects including weight
      bearing. Where outcome measures were similar, some data pooling was possible.
      RESULTS: There is good evidence that early motion is associated with a quicker
      return to work on average (p = 0.008) and also with an improved range of motion
      at 12 weeks (dorsiflexion p = 0.001; plantarflexion p < 0.00001) compared to cast
      immobilization. However it is also associated with an increased risk of wound
      infection (p = 0.002). There is a suggestion that early motion results in a lower
      rate of deep vein thrombosis (p = 0.12). There is no evidence that it results in
      improved joint specific outcome scores or range of motion at 1 year. CONCLUSION:
      It is difficult to conclude whether early motion is overall better or worse than
      cast immobilization. The evidence suggests however that a young fit patient who
      needs to return to work may benefit from early motion of the ankle joint whereas
      a patient with poor skin or at risk of infection may be better treated in a cast
      after surgery.

PMID- 19589315
TI  - Arthroscopic lateral release and percutaneous distal osteotomy for hallux valgus:
      a preliminary report.
AB  - Distal osteotomy of the first metatarsal is frequently used for the treatment of
      hallux valgus deformity. The great toe arthroscopy is a safe procedure to perform
      a distal soft tissue release and a complete evaluation of the first metatarsal
      phalangeal joint. The aim of this study was to evaluate the results of the
      arthroscopic distal soft tissue release with a distal percutaneous osteotomy in
      the treatment of hallux valgus deformity. From January 1, 2003, to August 1,
      2006, 59 consecutive procedures were performed in 49 patients. Clinical
      evaluation was calculated using the hallux score of the American Orthopedic Foot
      and Ankle Society (AOFAS). The mean follow up was 31.48 (range, 12 to 48) months
      and the AOFAS score improved from 45 (range, 30 to 65) points to 90.61 (range, 75
      to 100). The excellent results obtained encourage the authors to go on treat the
      hallux valgus deformity with this combination of two minimal invasive procedures.

PMID- 19589316
TI  - Minimally invasive paratenon release for non-insertional Achilles tendinopathy.
AB  - BACKGROUND: Non-insertional Achilles tendinopathy is an increasing, perhaps
      secondary to an increase in sporting activities. Traditional open surgical
      procedures have been associated with a significant rate of complications. We
      describe a minimally invasive technique involving the release of the adherent
      paratenon with a peritendinous infusion of corticosteroids and present the
      results in a cohort of patients. MATERIALS AND METHODS: Twenty-nine tendons (26
      patients) with non-insertional Achilles tendinopathy were treated with the above
      technique. Assessments were made prospectively using an adapted classification of
      Achilles tendon disability and a visual analogue scale for pain. Patients were
      interviewed in person or by telephone at an average of 14 (range, 6 to 30) months
      after surgery. RESULTS: The average pain score (VAS) improved from 8.7 to 2.4 (p
      < 0.001) and the average Puddu level of disability improved from 4.9 to 1.7 (p <
      0.001). Seventy-five percent of patients had a good or excellent outcome with 20%
      having sufficient improvement not to pursue further medical attention for their
      tendinopathy. There was a 7% rate of minor complications due to delayed wound
      healing which resolved spontaneously and did not affect the rehabilitation or the
      recovery of the patients. CONCLUSION: A minimally invasive circumferential
      paratenon release and peritendinous steroid infusion was a simple method to treat
      non-insertional Achilles tendinopathy and had low morbidity in our series. This
      technique has become our preferred primary surgical intervention for this
      condition.

PMID- 19589317
TI  - Locally generated bone slurry accelerated ankle arthrodesis.
AB  - BACKGROUND: Reported ankle fusion healing times vary between 7 to 72 weeks. High
      non-union and delayed union rates have led to an increased use of bone graft and
      bone graft substitutes. It was our goal to see if addition of a bone slurry could
      accelerate the rate of healing. MATERIALS AND METHODS: We compared the
      radiographic healing after ankle arthrodesis in two groups of patients treated
      over 3 years with and without a 'bone slurry.' In group one, a slurry of bone
      particles was generated with a low-speed burr and left in the joint before
      internal fixation. Group two had similar fixation but no bone slurry. Two
      reviewers, blinded to the presence or absence of slurry, studied magnified
      digital radiographs at 6 and 12 weeks. The percentage of the joint bridged by
      bone was recorded for each and the groups were averaged. Groups were compared
      using Wilcoxon rank sum. RESULTS: There were 32 patients in group one and 22 in
      group two. Groups were similar in age, gender and diagnosis. At 6 weeks, group
      one had 94.1% bridging bone, as measured on AP radiographs. Group two had 76.4%
      bridging bone. (Wilcoxon rank sum test p = 0.0099). At 12 weeks, group one had
      98.1% bridging bone and group two had 85.7% bridging bone (Wilcoxon rank sum test
      p = 0.026). CONCLUSION: Use of a low-speed burr to generate a "bone paste'' from
      the local bone surfaces was associated with an increased percentage of healed
      bone surface at 6 and 12 weeks in patients undergoing ankle arthrodesis.

PMID- 19589318
TI  - Accuracy of anterolateral drawer test in lateral ankle instability: a cadaveric
      study.
AB  - BACKGROUND: In the assessment of lateral ankle instability, the anterior drawer
      test has been found to be inaccurate and the focus on pure anterior translation
      cannot properly perceive the anterolateral rotatory nature of the talar
      displacement. In order to address this, the anterolateral drawer test can be done
      with digital palpation of the talar displacement anterolaterally with a
      controlled angle of plantarflexion as well as application of the translational
      force. MATERIALS AND METHODS: We evaluated the anterolateral drawer test and the
      original anterior drawer test in 10 fresh below-the-knee specimens using a direct
      anatomic measurement (DAM) loaded by a Telos stress device as a reference.
      Specimens were assigned into three groups: intact ligaments, ATFL-cut, and
      ATFL&CFL-cut. The examiners were blinded with one performing the anterolateral
      drawer test (E1) while the other performed the original anterior drawer test
      (E2). RESULTS: Pearson's correlation coefficient indicated a statistically
      significant linear relationship between DAM/E1 r = 0.931, p < 0.001 but not
      between DAM/E2 r = 0.519, p = 0.124. Intraclass correlation coefficient show
      correlation between DAM/E1 and DAM/E2 to be 0.945 (p < 0.001) and 0.683 (p =
      0.051). When 3 mm or more was used as the threshold to diagnose a lateral
      ligament rupture, sensitivity and specificity were E1(100%, 100%) and E2(75%,
      50%). CONCLUSION: The anterolateral drawer test showed high accuracy in the
      determination of lateral ankle instability and in the diagnosis of a ligament
      rupture. CLINICAL RELEVANCE: Further investigation regarding the accuracy and
      reliability of this test in comparison with the original anterior drawer test is
      warranted in a patient population with ankle instability.

PMID- 19589319
TI  - Comparison of augmentation methods for internal fixation of osteoporotic ankle
      fractures.
AB  - BACKGROUND: Internal fixation of osteoporotic ankle fractures is associated with
      failure of fixation. This study compared different augmentation methods
      biomechanically. MATERIALS AND METHODS: In nine paired fresh-frozen cadaver legs,
      an identical supination-external rotation type II ankle fracture was created.
      Fractures were stabilized using an eight-hole locking plate. In four pairs, two
      screws were inserted across the syndesmosis for purchase in the tibial
      metaphysis. One leg from each pair was randomly selected for injection of calcium
      sulphate-calcium phosphate graft into the screw holes. Each leg was mounted to an
      MTS machine in a custom loading frame. Axial cyclic loading to body weight was
      performed to measure displacement at the fracture site, followed by rotational
      loading to failure simulating a supination external rotation injury. Data were
      analyzed using a two-way paired t-test and ANOVA. RESULTS: The specimens used had
      a mean bone mineral density of 0.49 +/- 0.15 (SD) g/cm(2), and a mean age of 83
      +/- 12 years. In the biomechanical tests, there were no significant differences
      between augmented and non-augmented locking plates without the tibia-pro-fibula
      screws in axial stiffness (p = 0.10), external rotation angle at failure (p =
      0.42), failure torque (p = 0.57), energy absorbed before failure (p = 0.47), and
      motion at the fracture site with cyclic axial loading (p = 0.15). There were no
      significant differences between augmented and non-augmented locking plates with
      the tibia-pro-fibula screws in the external rotation angle at failure (p = 0.83),
      failure torque (p = 0.58), and failure energy (p = 0.4). However, the overall
      strength of the fixation tended to increase with tibia-pro-fibula screws and
      augmentation. CONCLUSION: Internal fixation of an osteoporotic lateral malleolar
      fracture using a locking plate and screws provided a construct comparable in
      strength to that augmented with calcium sulfate-calcium phosphate graft and/or
      tibia-pro-fibula screws. CLINICAL RELEVANCE: Strategies to augment internal
      fixation of osteoporotic ankle fractures may minimize risk for failure of
      fixation and may enable early weight bearing mobilization and return to function
      in elderly patients.

PMID- 19589320
TI  - Z shortening of healed Achilles tendon rupture: a technical note.

PMID- 19589321
TI  - Clinical tip: the reverse coleman block test radiograph.

PMID- 19589322
TI  - Technique tip: a simple method of footwear attachment for circular frames.

PMID- 19589323
TI  - Technique tip: the use of a washer and suture endobutton in revision lisfranc
      fixation.

PMID- 19589324
TI  - Total calcanectomy and reconstruction with vascularized iliac bone graft for
      osteoblastoma: a report of two cases.

PMID- 19589325
TI  - FootForum: Pay for Performance (P4P) Initiatives.

PMID- 19589327
TI  - Foresight Infectious Diseases China Project--a novel approach to anticipating
      future trends in risk of infectious diseases in China: methodology and results
      from an initial application.
AB  - The project devised a simple but novel methodology for identifying possible
      future trends in infectious diseases in animals and humans in China, of priority
      concern to the Chinese authorities. It used a model of disease drivers (social,
      economic, biological or environmental factors that affect disease outcomes, by
      changing the behaviour of diseases, sources or pathways) devised for the
      Foresight Programme in the United Kingdom. Nine families of drivers were adapted
      to Chinese circumstances and matrices were constructed to identify the likely
      relationship of single infectious diseases or families of diseases to the
      drivers. The likely future trends in those drivers in China were determined by
      interviews with 36 independent Chinese experts. These trends included not only
      potentially adverse animal and human movements but also opportunities for
      innovative surveillance methods, more use of hospitals, antimicrobials and
      vaccines. Some human behaviours and social trends were expected to increase the
      risk of infections (in particular sexually transmitted and healthcare-associated
      infections) while at the same time the experts thought the awareness of risk in
      the Chinese population would increase. The results suggested a number of areas
      where the Chinese authorities may experience difficulties in the future, such as
      rising numbers of healthcare-associated infections, zoonoses and other emerging
      diseases and sexually transmitted infections (including HIV). Not making firm
      predictions, this work identifies priority disease groups requiring surveillance
      and consideration of countermeasures as well as recommending strengthening basic
      surveillance and response mechanisms for unanticipatable zoonoses and other
      emerging disease threats.

PMID- 19589328
TI  - Outbreak of influenza A(H1N1)v without travel history in a school in the Toulouse
      district, France, June 2009.
AB  - In June 2009, for the first time in France, a confirmed outbreak of influenza
      A(H1N1)v without history of travel occurred in a secondary school in Toulouse
      district. A total of 15 cases were confirmed among students of which three were
      asymptomatic. This report describes the outbreak and its public health
      implications.

PMID- 19589329
TI  - Preliminary descriptive epidemiology of a large school outbreak of influenza
      A(H1N1)v in the West Midlands, United Kingdom, May 2009.
AB  - This report describes the preliminary results from the investigation of a large
      school outbreak of influenza A(H1N1)v in Birmingham, United Kingdom in May 2009,
      when influenza A(H1N1)v was confirmed in 64 of 175 (36%) symptomatic pupils and
      members of staff.

PMID- 19589330
TI  - An outbreak of influenza A(H1N1)v in a boarding school in South East England, May
      June 2009.
AB  - An outbreak of influenza A(H1N1)v was confirmed in May and June 2009 in a
      boarding school in South East England involving 102 symptomatic cases with
      influenza-like illness. Influenza A(H1N1)v infection was laboratory-confirmed by
      PCR in 62 pupils and one member of staff.

PMID- 19589331
TI  - Enhanced epidemiological surveillance of influenza A(H1N1)v in Italy.
AB  - As of 7 July 2009, a total of 158 laboratory-confirmed cases of influenza
      A(H1N1)v were reported in Italy, from half of the 21 Italian regions. To date all
      cases have had symptoms consistent with seasonal influenza and no severe or fatal
      cases have been reported. An active surveillance of cases has been set up in
      Italy in order to undertake appropriate measures to slow down the spread of the
      new virus. This report describes the routine and enhanced surveillance currently
      ongoing in Italy.

PMID- 19589332
TI  - Epidemiology and control of influenza A(H1N1)v in the Netherlands: the first 115
      cases.
AB  - Introductions of the new influenza A(H1N1) variant virus in the Netherlands led
      to enhanced surveillance and infection control. By 24 June 2009, 115 cases were
      reported, of whom 44% were indigenously acquired. Severity of disease is similar
      to reports elsewhere. Our point estimate of the effective reproductive number
      (Re) for the initial phase of the influenza A(H1N1)v epidemic in the Netherlands
      was below one. Given that the Re estimate is based on a small number of
      indigenous cases and a limited time period, it needs to be interpreted
      cautiously.

PMID- 19589333
TI  - Characterization of cluster-assembled nanostructured titanium oxide coatings as
      substrates for protein arrays.
AB  - Protein microarray technologies are rapidly expanding to fulfill current needs of
      proteome discovery for disease management. Nanostructured materials have been
      shown to present interesting features when used in biological settings:
      nanostructured titanium oxide film (ns-TiOx), synthesized by supersonic cluster
      beam deposition (SCBD), has recently emerged as a biocompatible substrate in
      different biological assays. The ns-TiOx surface is characterized by a morphology
      at the nanoscale that can be tuned to modulate specific biomolecule-material
      interactions. Here we present a systematic characterization of ns-TiOx coatings
      as protein binding surfaces, comparing their performances with those of most
      common commercial substrates in protein and antibody microarray assays. Through a
      robust statistical evaluation of repeatability in terms of coefficient of
      variation (CV) analysis, we demonstrate that ns-TiOx can be used as reliable
      substrate for biochips in analytical protein microarray application.

PMID- 19589334
TI  - Spinal ERK activation via NO-cGMP pathway contributes to nociceptive behavior
      induced by morphine-3-glucuronide.
AB  - Intrathecal (i.t.) injection of morphine-3-glucuronide (M3G), a major metabolite
      of morphine without analgesic actions, produces a severe hindlimb scratching
      followed by biting and licking in mice. The pain-related behavior evoked by M3G
      was inhibited dose-dependently by i.t. co-administration of tachykinin NK(1)
      receptor antagonists, sendide, [D-Phe(7), D-His(9)] substance P(6-11), CP-99994
      or RP-67580 and i.t. pretreatment with antiserum against substance P. The
      competitive NMDA receptor antagonists, D-APV and CPP, the NMDA ion-channel
      blocker, MK-801 or the competitive antagonist of the polyamine recognition site
      of NMDA receptor ion-channel complex, ifenprodil, produced inhibitory effects on
      i.t. M3G-evoked nociceptive response. The NO-cGMP-PKG pathway, which involves the
      extracellular signal-regulated kinase (ERK), has been implicated as mediators of
      plasticity in several pain models. Here, we investigated whether M3G could
      influence the ERK activation in the NO-cGMP-PKG pathway. The i.t. injection of
      M3G evoked a definite activation of ERK in the lumbar dorsal spinal cord, which
      was prevented dose-dependently by U0126, a MAP kinase-ERK inhibitor. The
      selective nNOS inhibitor N(omega)-propyl-l-arginine, the selective iNOS inhibitor
      W1400, the soluble guanylate cyclase inhibitor ODQ and the PKG inhibitor KT-5823
      inhibited dose-dependently the nociceptive response to i.t. M3G. In western
      blotting analysis, inhibiting M3G-induced nociceptive response using these
      inhibitors resulted in a significant blockade of ERK activation induced by M3G in
      the spinal cord. Taken together, these results suggest that activation of the
      spinal ERK signaling in the NO-cGMP-PKG pathway contributes to i.t. M3G-evoked
      nociceptive response.

PMID- 19589335
TI  - Towards the mechanism and comparative effect of diphenyl diselenide, diphenyl
      ditelluride and ebselen under various pathophysiological conditions in rat's
      kidney preparation.
AB  - As an extension of our previous work we not only evaluated the relationship
      between acidosis and lipid peroxidation in rat's kidney homogenate, but also
      determined for the first time the potential anti-oxidant activity of diphenyl
      diselenide, diphenyl ditelluride and ebselen at a range of pH values (7.4-5.4).
      Because of the pH dependency of iron redox cycling, pH and iron need to be well
      controlled and for the reason we tested a number of pH values (from 7.4 to 5.4)
      to get a closer idea about the role of iron under various pathological
      conditions. Acidosis increased rate of lipid peroxidation in the absence Fe (II)
      in kidney homogenates especially at pH 5.4. This higher extent of lipid
      peroxidation can be explained by; the mobilized iron which may come from reserves
      where it is weakly bound. Addition of iron (Fe) chelator desferoxamine (DFO) to
      reaction medium completely inhibited the peroxidation processes at all studied pH
      values including acidic values (5.8-5.4). In the presence of Fe (II) acidosis
      also enhanced detrimental effect of Fe (II) especially at pH (6.4-5.4). Diphenyl
      diselenide significantly protected lipid peroxidation at all studied pH values,
      while ebselen offered only a small statistically non-significant protection. The
      highest anti-oxidant potency was observed for diphenyl ditelluride. These
      differences in potencies were explained by the mode of action of these compounds
      using their catalytic anti-oxidant cycles. However, changing the pH of the
      reaction medium did not alter the anti-oxidant activity of the tested compounds.
      This study provides evidence for acidosis catalyzed oxidative stress in kidney
      homogenate and for the first time anti-oxidant potential of diphenyl diselenide
      and diphenyl ditelluride not only at physiological pH but also at a range of
      acidic values.

PMID- 19589337
TI  - Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus
      ligature-induced gastric ulcer in rats.
AB  - Zn(II)-curcumin, a mononuclear (1:1) zinc complex of curcumin was synthesized and
      examined for its antiulcer activities against pylorus-ligature-induced gastric
      ulcer in rats. The structure of Zn(II)-curcumin was identified by elemental
      analysis, NMR and TG-DTA analysis. It was found that a zinc atom was coordinated
      through the keto-enol group of curcumin along with one acetate group and one
      water molecule. Zn(II)-curcumin (12, 24 and 48 mg/kg) dose-dependently blocked
      gastric lesions, significantly reduced gastric volume, free acidity, total
      acidity and pepsin, compared with control group (P<0.001) and curcumin alone (24
      mg/kg, P<0.05). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis
      showed that Zn(II)-curcumin markedly inhibited the induction of nuclear factor
      kappa B (NF-kappaB), transforming growth factor beta(1) (TGF-beta(1)) and
      interleukin-8 (IL-8), compared with control group (P<0.05). These findings
      suggested that Zn(II)-curcumin prevented pylorus-ligation-induced lesions in rat
      by inhibiting NF-kappaB activation and the subsequent production of
      proinflammatory cytokines, indicating a synergistic effect between curcumin and
      zinc. An acute toxicity study showed that mice treated with SDs of Zn(II)
      curcumin (2 g/kg) manifested no abnormal signs.

PMID- 19589336
TI  - Operculina turpethum attenuates N-nitrosodimethylamine induced toxic liver injury
      and clastogenicity in rats.
AB  - The root extract of Operculina turpethum (OTE) has been used as an anti
      inflammatory, purgative, and hepato-protective agent. N-Nitrosodimethylamine
      (NDMA) is a potent hepatotoxin that induces fibrosis of the liver. In the present
      study, we examined the therapeutic effects of OTE root extract against NDMA
      induced hepatotoxicity and clastogenicity in rats. Hepatic fibrosis was induced
      in adult male albino rats through serial intraperitoneal administrations of NDMA
      at a concentration of 10mg/kg body weight on three consecutive days of each week
      over a period of three weeks. A group of rats received OTE orally in doses of 75,
      150 and 200mg/kg body weight at 5h after the administration of NDMA. The controls
      and treated animals were sacrificed on days-7, 14 and 21 after the start of the
      administration of NDMA. The progression of hepatic fibrosis as well as the
      amelioration effect of OTE was evaluated through histopathologically as well as
      by immunohistochemical staining for the activation of hepatic stellate cells.
      Alterations in serum and liver biochemical parameters and LDH isoenzymes were
      also studied. Serial administration of NDMA resulted in well formed fibrosis in
      the liver and induction of micronuclei in the bone marrow cells. Staining of
      alpha-SMA demonstrated activated stellate cells from day-7 onwards which was
      dramatically increased on day-21. An elevation of micronuclei count, liver
      function enzymes, serum hydroxyproline levels and LDH isoenzymes 4 and 5 were
      also observed. All these changes were remarkably reduced in OTE administered
      animals and fibrogenesis was completely absent. Our results suggest that OTE has
      hepatoprotective and anti-clastogenic effects against NDMA-induced hepatic
      fibrosis. Therefore OTE may be used as a hepatoprotective agent against various
      liver diseases including toxic liver injury.

PMID- 19589338
TI  - Variation patterns of two degradation enzyme systems in articular cartilage in
      different stages of osteoarthritis: regulation by dehydroepiandrosterone.
AB  - BACKGROUND: Osteoarthritis (OA) is a multifactorial degenerative joint disease in
      which the cartilaginous matrix of the articular joint is destroyed in a
      continuous process. We evaluated mRNA levels of cysteine proteinases/cystatin C
      system and urokinase plasminogen activator/plasminogen activator inhibitor-1
      (uPA/PAI-1) system in articular cartilage and regulation by
      dehydroepiandrosterone (DHEA) in different stages of osteoarthritis (OA).
      METHODS: One hundred and eight rabbits underwent anterior cruciate ligament
      transection (ACLT) in the left knee, 54 received weekly intra-articular
      injections of DHEA (100 micromol/l) 0.3 ml 3 weeks after transaction as DHEA
      group. Thirty-six rabbits (18 from 2 groups respectively) were euthanized 6, 9,
      and 12 weeks after ACLT. All left knee joints were assessed by gross morphology
      and histology, meantime the gene expression from articular cartilage was
      analyzed. RESULTS: Cathepsins and uPA gene increased significantly 6 weeks and
      reached peak in the 9th week, while declined to extremely low levels 12 weeks
      after ACLT. Cystatin C decreased accompanied by OA progression, while PAI-1
      expressed in the same trend with uPA. Additionally, these 2 enzyme systems were
      markedly suppressed by DHEA 6 and 9 weeks after ACLT but not in the 12th week.
      CONCLUSION: The variation of these 2 enzyme systems was closely related to the
      progression of OA, and could be regulated by DHEA especially in the early and
      medium stages of OA.

PMID- 19589339
TI  - Selective arginines are important for the antibacterial activity and host cell
      interaction of human alpha-defensin 5.
AB  - Defensins constitute a major family of natural antimicrobial peptides that
      protect the host against microbial invasion. Here, we report on the antibacterial
      properties and cellular interaction of Human Defensin 5 as a function of its
      positive charge and hydrophobicity. We find that selective replacement of
      arginine residues in HD-5 by alanine or charge-neutral lysine residues reduces
      antibacterial killing as well as host cell interaction. We identify arginines at
      positions 9 and 28 in the HD-5 sequence as particularly important for its
      function. Replacement of arginine at position 13 to Histidine, as observed in a
      Crohn's disease patient, reduced bacterial killing strain-selectively. Finally,
      we find that HD-5 interacts with host cells via receptor-mediated mechanisms.

PMID- 19589341
TI  - Thermoregulation of water foraging wasps (Vespula vulgaris and Polistes
      dominulus).
AB  - A comparison of the thermoregulation of water foraging wasps (Vespulavulgaris,
      Polistesdominulus) under special consideration of ambient temperature and solar
      radiation was conducted. The body surface temperature of living and dead wasps
      was measured by infrared thermography under natural conditions in their
      environment without disturbing the insects' behaviour. The body temperature of
      both of them was positively correlated with T(a) and solar radiation. At moderate
      T(a) (22-28 degrees C) the regression lines revealed mean thorax temperatures
      (T(th)) of 35.5-37.5 degrees C in Vespula, and of 28.6-33.7 degrees C in
      Polistes. At high T(a) (30-39 degrees C) T(th) was 37.2-40.6 degrees C in Vespula
      and 37.0-40.8 degrees C in Polistes. The thorax temperature excess (T(th)-T(a))
      increased at moderate T(a) by 1.9 degrees C (Vespula) and 4.4 degrees C
      (Polistes) per kW(-1)m(-2). At high T(a) it increased by 4.0 degrees C per kW(
      1)m(-2) in both wasps. A comparison of the living water foraging Vespula and
      Polistes with dead wasps revealed a great difference in their thermoregulatory
      behaviour. At moderate T(a) (22-28 degrees C) Vespula exhibited distinct
      endothermy in contrast to Polistes, which showed only a weak endothermic
      activity. At high T(a) (30-39 degrees C) Vespula reduced their active heat
      production, and Polistes were always ectothermic. Both species exhibited an
      increasing cooling effort with increasing insolation and ambient temperature.

PMID- 19589340
TI  - Intracellular ANKRD1 protein levels are regulated by 26S proteasome-mediated
      degradation.
AB  - The ANKRD1/CARP gene encodes a muscle-specific protein which has been implicated
      in transcriptional regulation and myofibrillar assembly. Several features at both
      the mRNA and protein levels define ANKRD1 as a gene whose expression is tightly
      regulated, and deregulated expression of this protein has been recently
      associated to human congenital heart disease. It is therefore crucial to define
      the intracellular pathways that regulate the ANKRD1 protein's steady-state
      levels. Here, we show that ANKRD1 is a short-lived protein whose levels are
      tightly regulated by the 26S proteasome. In addition, a critical role for a
      putative PEST motif was established, although other degrons within the ANKRD1
      protein are likely implicated in the control of its intracellular levels.

PMID- 19589342
TI  - Age and size thresholds for pupation and developmental polymorphism in the
      browntail moth, Euproctis chrysorrhoea (Lepidoptera: Lymantriidae), under
      conditions that either emulate diapause or prevent it.
AB  - Size and age thresholds for pupation are important life history traits of
      insects. They are the ultimate consequences of the underlying physiological
      mechanism that optimize resource allocation. Such thresholds may have a plastic
      response under time-varying environmental conditions, developmental polymorphism
      (i.e., plasticity in the number of instars before pupation) being a common
      strategy adopted by insects to overcome this challenging situation. In this
      study, we systematically explore the variables related with both age and size
      thresholds for pupation and developmental polymorphism in the browntail moth,
      Euproctis chrysorrhoea (Lepidoptera: Lymantriidae), by rearing a group of
      caterpillars under conditions that either emulate larval diapause or prevent it.
      As an innovative approach, we evaluated the importance of predictor variables by
      means of generalized linear modeling in a multi-model inference framework. Our
      results show that (i) rearing conditions affect fitness, (ii) rearing conditions,
      size of hatchlings, size and age at maturity and sex are related to the number of
      instars before pupation, and (iii) there are both age and size thresholds for
      pupation which differ between sexes and between larvae reared under different
      conditions. Results are discussed in the context of lepidopteran plasticity in
      life history traits and its relationship with optimal molting strategies.

PMID- 19589343
TI  - Mathematical modeling of the lambda switch: a fuzzy logic approach.
AB  - Gene regulation plays a central role in the development and functioning of living
      organisms. Gaining a deeper qualitative and quantitative understanding of gene
      regulation is an important scientific challenge. The Lambda switch is commonly
      used as a paradigm of gene regulation. Verbal descriptions of the structure and
      functioning of the switch have appeared in biological textbooks. We apply fuzzy
      modeling to transform one such verbal description into a well-defined
      mathematical model. The resulting model is a piecewise-quadratic second-order
      differential equation. It demonstrates functional fidelity with known results
      while being simple enough to allow a rather detailed analysis. Properties such as
      the number, location, and domain of attraction of equilibrium points can be
      studied analytically. Furthermore, the model provides a rigorous explanation for
      the so-called stability puzzle of the Lambda switch.

PMID- 19589344
TI  - Disentangling nature, strength and stability issues in the characterization of
      population interactions.
AB  - Many recent reviews discuss the adequacy of definitions and metrics for the
      strength of population interactions. However, the discussion on the beneficial or
      detrimental nature of interactions is clearly absent, or at the most,
      inadvertently merged into the strength debate. This deficiency is emerging with
      the increasing interest in theoretical studies of interactions that shift in
      their nature; e.g. associations that present a mixture of mutualistic and
      antagonistic aspects, such as pollination; or species with changes in role, such
      as mutualistic ants that predate on aphid partners. By exploring these models,
      major controversies are revealed underlying some traditional perspectives: the
      original Levins'community matrix reformulated into interaction and jacobian
      matrices, that is, interaction coefficients reinterpreted as partial derivatives,
      fail to recognize the ecological context of interactions. The 'effect of one
      species on the other' is not necessarily quantified by 'the effect of varying
      species densities'; and shifts in the signs of jacobian elements do not
      correspond to shifts in types of interaction but to stability properties. Thus,
      the generalised use of these approaches must be revised. On the other hand, the
      comparison of ultimate performances of populations when growing alone or in
      association, here referred to as the relative performance approach, conceptually
      represents the original meaning of the community matrix. This conception,
      although measured at population levels, is a reflection of properties at the
      individual level. This article inspects and discusses the formalities and
      ecological contexts of these approaches to characterization by means of known
      population interaction models: linear and non-linear, variable and non-variable;
      aiming to disentangle crucial conceptions that are usually mingled in the
      literature: the strength (magnitude) and the nature (detrimental or beneficial)
      of the interaction, which are sometimes used interchangeably, and the stability
      properties of the system, which have been misleadingly associated with the
      latter.

PMID- 19589345
TI  - Gene-smoking interaction on colorectal adenoma and cancer risk: review and meta
      analysis.
AB  - The etiology of colorectal cancer is complex and multifactorial. Tobacco smoke
      has been found to be associated both with colorectal adenoma and cancer
      development. It was hypothesized that tobacco smoking could interact with genetic
      factors, providing different risk estimates according to different genetic
      predisposition. We reviewed and summarized by a meta-analytic approach the
      evidence from the literature on the interaction of smoking with the five most
      studied gene polymorphisms (GSTM1, GSTT1, mEH3, mEH4, NAT2). We calculated pooled
      Odds Ratios for each gene-smoking combination by random effects models, and
      provided a pooled P-value for gene-smoking interaction. Heterogeneity among
      studies was evaluated by the Q statistic and I(2). Overall, 27 case-control
      studies or nested case-control studies are included in this review: 12 presented
      data on GSTM1 polymorphism, eight on GSTT1, seven on mEH3, mEH4, and 10 on NAT2.
      We found a weak suggestion of an antagonistic effect of mEH3 low or medium
      metabolizer with smoking on colorectal adenoma risk (pooled P-value for the
      interaction: 0.02): smokers carriers of mEH3 low or medium metabolizer had
      slightly lower risk (Odds Ratio; 95% Confidence Interval: 1.6; 1.2-2.1) than
      smokers with mEH3 high metabolizer (1.8; 1.4-2.4). A non-significant positive
      interaction between GSTT1 null genotype and smoking was suggested for colorectal
      adenoma risk. None of the other common genetic polymorphisms involved in tobacco
      carcinogens metabolism seemed to modify the smoking-related risk of colorectal
      adenoma or cancer.

PMID- 19589346
TI  - Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout
      mice.
AB  - Previous studies have implicated a potential role for histamine H3 receptor in
      pain processing. There have been conflicting data, however, on the roles of H3
      receptors in pain perception, and little information is available about the role
      of spinal histamine H3 receptors in morphine-induced antinociception. In the
      present study we examined the role of histamine H3 receptor in morphine-induced
      antinociception using histamine H3 receptor knockout mice and a histamine H3
      receptor antagonist. Anitinociception was evaluated by assays for four
      nociceptive stimuli: hot-plate, tail-flick, paw-withdrawal, and formalin tests.
      Antinociception induced by morphine (0.125 nmol/5 microl, i.t.) was significantly
      augmented in histamine H3 receptor knockout (-/-) mice compared to the wild-type
      (+/+) mice in all four assays of pain. Furthermore, the effect of intrathecally
      administered morphine with thioperamide, a histamine H3 antagonist, was examined
      in C57BL/6J mice. A low dose of i.t. administered thioperamide (0.125 nmol/5
      microl) alone had no significant effect on the nociceptive response. In contrast,
      the combination of morphine (0.125 nmol/5 microl, i.t.) with the same dose of
      thioperamide resulted in a significant reduction in the pain-related behaviors in
      all four nociceptive tests. These results suggest that histamine exerts
      inhibitory effects on morphine-induced antinociception through H3 receptors at
      the spinal level.

PMID- 19589347
TI  - Oxytocin enhances the inhibitory effects of diazepam in the rat central medial
      amygdala.
AB  - Oxytocin is a neuropeptide that can reduce neophobia and improve social
      affiliation. In vitro, oxytocin induces a massive release of GABA from neurons in
      the lateral division of the central amygdala which results in inhibition of a
      subpopulation of peripherally projecting neurons in the medial division of the
      central amygdala (CeM). Common anxiolytics, such as diazepam, act as allosteric
      modulators of GABA(A) receptors. Because oxytocin and diazepam act on GABAergic
      transmission, it is possible that oxytocin can potentiate the inhibitory effects
      of diazepam if both exert their pre, - respectively postsynaptic effects on the
      same inhibitory circuit in the central amygdala. We found that in CeM neurons in
      which diazepam increased the inhibitory postsynaptic current (IPSC) decay time,
      TGOT (a specific oxytocin receptor agonist) increased IPSC frequency. Combined
      application of diazepam and TGOT resulted in generation of IPSCs with increased
      frequency, decay times as well as amplitudes. While individual saturating
      concentrations of TGOT and diazepam each decreased spontaneous spiking frequency
      of CeM neurons to similar extent, co-application of the two was still able to
      cause a significantly larger decrease. These findings show that oxytocin and
      diazepam act on different components of the same GABAergic circuit in the central
      amygdala and that oxytocin can facilitate diazepam effects when used in
      combination. This raises the possibility that neuropeptides could be clinically
      used in combination with currently used anxiolytic treatments to improve their
      therapeutic efficacy.

PMID- 19589348
TI  - Antidepressant like effect of selective serotonin reuptake inhibitors involve
      modulation of imidazoline receptors by agmatine.
AB  - Recent findings demonstrated the dysregulation of imidazoline receptor binding
      sites in major depression and their normalization by chronic treatment with
      antidepressants including selective serotonin reuptake inhibitors (SSRIs).
      Present study investigated the role of agmatine and imidazoline receptors in
      antidepressant like effect of SSRIs and imipramine in mouse forced swimming test
      (FST) paradigm. The antidepressant like effect of fluoxetine or paroxetine was
      potentiated by imidazoline I(1)/I(2) receptor agonist agmatine (5-10 mg/kg, ip),
      imidazoline I(1) receptor agonists, moxonidine (0.25-0.5 mg/kg, ip) and clonidine
      (0.015-0.03 mg/kg, ip), imidazoline I(2) receptor agonist, 2-(2-benzofuranyl)-2
      imidazoline (5-10 mg/kg, ip) as well as by the drugs known to increase endogenous
      agmatine levels in brain viz., L-arginine, an agmatine biosynthetic precursor (40
      microg/mouse, icv), ornithine decarboxylase inhibitor, difluoromethyl ornithine
      (12.5 microg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5
      microg/mouse, icv) and agmatinase inhibitor, arcaine (50 microg/mouse, icv).
      Conversely, prior administration of I(1) receptor antagonist, efaroxan (1 mg/kg,
      ip), I(2) receptor antagonist, idazoxan (0.25 mg/kg, ip) and arginine
      decarboxylase inhibitor, d-arginine (100 mg/kg, ip) blocked the antidepressant
      like effect of paroxetine (10 mg/kg, ip) and fluoxetine (20 mg/kg, ip). On the
      other hand, antidepressant like effect of imipramine was neither augmented nor
      attenuated by any of the above drugs. Mice pretreated with SSRIs but not
      imipramine and exposed to FST showed higher concentration of agmatine in brain as
      compared to saline control. This effect of SSRIs on agmatine levels was
      completely blocked by arginine decarboxylase inhibitor d-arginine but not by
      imidazoline receptor antagonists, efaroxan or idazoxan. These results demonstrate
      that modulation of imidazoline receptors by agmatine are implicated in the
      antidepressant like effect of SSRIs and may be projected as a potential
      therapeutic target for the treatment of depressive disorders.

PMID- 19589349
TI  - Chronic icv oxytocin attenuates the pathological high anxiety state of
      selectively bred Wistar rats.
AB  - Central oxytocin (OXT) has been shown to promote numerous social behaviours, to
      attenuate hormonal stress responsiveness of the HPA axis and to decrease anxiety.
      Wistar rats selectively bred for high (HAB) and low (LAB) anxiety-related
      behaviour, respectively, have been shown to represent a suitable animal model to
      study the underlying aetiology of psychopathologies like anxiety- and depression
      related disorders. The goal of the present studies was to assess the effects of
      central OXT on anxiety- and depression-related behaviour in male and female HAB
      and LAB rats. Acute icv OXT (1 microg) or OXT receptor antagonist (OXT-A; 0.75
      microg) administration did not affect anxiety-related behaviour in male or female
      HAB and LAB rats as assessed in the light-dark box. In contrast, chronic icv OXT
      infusion (10 ng/h; 6 d) attenuated the high level of anxiety-related behaviour in
      female, but not male, HAB rats, whereas chronic OXT-A infusion (7.5 ng/h; 6 d)
      increased anxiety-related behaviour in female, but not male, LAB rats. Neither
      acute nor chronic manipulation of the OXT system altered depression-related
      behaviour as assessed by the forced swim test. Combined, these results suggest
      that pharmacological manipulation of the brain OXT system is effective to
      attenuate extremes in trait anxiety in an animal model of psychopathological
      anxiety. Moreover, the data indicate that differences in the activity of the
      brain OXT systems between HAB and LAB rats may, at least partially, contribute to
      the opposing anxiety but not depression-related behaviour.

PMID- 19589350
TI  - Dual action of a dinoflagellate-derived precursor of Pacific ciguatoxins (P-CTX
      4B) on voltage-dependent K(+) and Na(+) channels of single myelinated axons.
AB  - The effects of Pacific ciguatoxin-4B (P-CTX-4B, also named gambiertoxin),
      extracted from toxic Gambierdiscus dinoflagellates, were assessed on nodal K(+)
      and Na(+) currents of frog myelinated axons, using a conventional voltage-clamp
      technique. P-CTX-4B decreased, within a few minutes, both K(+) and Na(+) currents
      in a dose-dependent manner, without inducing any marked change in current
      kinetics. The toxin was more effective in blocking K(+) than Na(+) channels. P
      CTX-4B shifted the voltage-dependence of Na(+) conductance by about 14 mV towards
      more negative membrane potentials. This effect was reversed by increasing Ca(2+)
      in the external solution. A negative shift of about 16 mV in the steady-state
      Na(+) inactivation-voltage curve was also observed in the presence of the toxin.
      Unmodified and P-CTX-4B-modified Na(+) currents were similarly affected by the
      local anaesthetic lidocaine. The decrease of the two currents by lidocaine was
      dependent on both the concentration and the membrane potential during pre-pulses.
      In conclusion, P-CTX-4B appears about four times more effective than P-CTX-1B to
      affect K(+) channels, whereas it is about 50 times less efficient to affect Na(+)
      channels of axonal membranes. These actions may be related to subtle differences
      between the two chemical structures of molecules.

PMID- 19589351
TI  - Engagement in cultural activities and cause-specific mortality: prospective
      cohort study.
AB  - OBJECTIVE: To determine the relation between engagement in cultural activities
      and main causes of mortality among full-time employees. METHODS: Finnish
      industrial employees (N=7922) completed a questionnaire about engagement in
      cultural activities (arts and culture, activities in associations, societal
      action, reading literature, and studying) in 1986 and were followed-up for
      mortality rates until 1986-2004. RESULTS: High engagement in cultural activities
      was independently associated with decreased all-cause mortality (hazard ratio
      0.71, 95% CI 0.57-0.88) and external causes of death (hazard ratio 0.46, 95% CI
      0.24-0.90) after adjustment for socio-demographic factors, socio-economic status,
      work stress, social characteristics, diabetes, and hypertension. High engagement
      was also associated with a reduced risk of cardiovascular mortality after
      controlling for socio-demographic factors and stress (hazard ratio 0.68, 95% CI
      0.49-0.95). The associations with all-cause mortality and deaths from external
      causes remained after further adjustment for behavioral risk factors. Of the
      forms of engagement, solitary cultural activities were related to all-cause
      mortality while socially shared cultural activities were more closely linked to
      external mortality. CONCLUSION: Better overall survival of culturally engaged
      employees is largely attributable to their lower risk of death from external
      causes.

PMID- 19589352
TI  - Physical activity promotion as a strategic corporate priority to improve worker
      health and business performance.
AB  - BACKGROUND: The increasingly sedentary nature of work and its impact on health
      and productivity indicators demands the promotion of physical activity at the
      worksite. PURPOSE: This paper aims to present considerations for broad-scale
      application of corporate strategies designed to promote physical activity among
      employees and their families through employer-sponsored initiatives. APPROACH:
      The benefits of physical activity are multifold, including health and wellbeing
      and productivity related outcomes. The workplace setting may be leveraged to
      promote physical activity levels through frequent and sustained exposures to
      effective interventions that reach employees and, indirectly, their families.
      Furthermore, employers represent a powerful stakeholder group that should
      leverage its influence on health policy initiatives designed to create supportive
      environments inside the workplace as well as the broader community. Specific
      principles, recommendations for action, and considerations for the prioritization
      of initiatives are provided based on essential elements for comprehensive
      programs and health policy initiatives and in the context of a social-ecological
      model and supportive research. CONCLUSIONS: Physical activity promotion at the
      worksite should be an integrated initiative that measurably improves worker
      health and enhances business performance.

PMID- 19589353
TI  - Do indoor smoke-free laws provide bar workers with adequate protection from
      secondhand smoke?
AB  - OBJECTIVE: To determine if bar workers are adequately protected from secondhand
      smoke by an Act that prohibits indoor smoking in public workplaces, including
      bars and restaurants, but allows smoking on unenclosed contiguous patios.
      METHODS: A purposive sample of 25 bars with outdoor patios in Toronto, Canada was
      drawn. Air carcinogenic particulate polycyclic aromatic hydrocarbons (PPAH) were
      measured on patios and inside bars in August-September, 2006, 2-3 months after
      implementation of the Smoke-Free Ontario Act. Taking into account repeated
      measures, mixed model analysis was applied to examine the level of fine particle
      PPAH (ng/m(3)) by number of lit cigarettes per patio area. RESULTS: Smoking on
      patios was common. With increasing numbers (0, 1.0-4.3, 4.4-8.7, 8.8-16.7 and
      16.8-41.7) of lit cigarettes per 1000 ft(2) of patio area, there were increases
      in geometric mean (geometric standard deviation) PPAH levels, 4.7 (2.4), 9.1
      (3.7), 16.9 (2.9), 19.1 (3.0) and 27.0 (2.9) ng/m(3) on patios. Mixed model
      analysis showed that PPAH levels increased significantly with number of lit
      cigarettes per patio area (p=0.0004). High levels of PPAH on patios may be
      associated with sustained vascular injury. CONCLUSIONS: Complete smoking bans
      including outdoor workspaces are needed to adequately protect hospitality workers
      from secondhand smoke.

PMID- 19589354
TI  - Measurement error and ethnic comparisons of measures of abdominal obesity.
AB  - BACKGROUND: Methods of estimating central obesity are important because of the
      increasing frequency of obesity related diseases worldwide. Here we evaluate the
      precision of measuring waist circumference and the waist to hip ratio with
      comparisons across ethnic groups. METHODS: The third Australian Risk Factor
      Prevalence Study (1989) of 9279 adults recorded height, weight, and Body Mass
      Index together with duplicate measurements of the waist and hip circumferences,
      the waist to hip ratio, and blood pressure levels using clearly defined survey
      techniques. Measurement error and precision for these variables were calculated,
      and comparisons were made across ethnic groups. RESULTS: Coefficients of
      variation for the waist circumference and the waist to hip ratio were less than
      1% indicating good precision in comparison with quite large variability for
      systolic and diastolic pressure readings. Waist circumference showed increased
      variability in subjects with larger body build in comparison with waist to hip
      ratio. Equivalence tests across ethnic groups indicated that the waist to hip
      ratio was independent of ethnicity. CONCLUSION: Waist to hip ratio provides a
      superior measure of central obesity with low measurement error, high precision,
      and no bias over a wide range of ethnic groups. We believe that it is essential
      to standardize methods in the assessment of central obesity. Assessment criteria
      should be based on waist to hip ratio rather than waist circumference.

PMID- 19589355
TI  - Functional similarities and distance properties.
AB  - The analysis of functional and effective brain connectivity forms an important
      tool for unraveling structure-function relationships from neurophysiological
      data. It has clinical applications, supports the formulation of hypotheses
      regarding the role and localization of functional processes, and is often an
      initial step in modeling. However, only a few of the commonly applied
      connectivity measures respect metric properties: reflexivity, symmetry, and the
      triangle inequality. This may hamper interpretation of findings and subsequent
      analysis. Connectivity indices obtained by metric measures can be seen as
      functional distances, and may be represented in Euclidean space by the methods of
      multidimensional scaling. We sketch some classes of measures that do allow for
      such a reconstruction, in particular the class of Wasserstein distances, and
      discuss their merits for interpreting cortical activity assessed by
      magnetoencephalography. In an application to magnetoencephalographic recordings
      during the execution of a bimanual task, the Wasserstein distances between
      relative circular variances indicated cortico-muscular synchrony as well as cross
      talk between bilateral primary motor areas in the beta-band.

PMID- 19589356
TI  - Oscillatory brain states interact with late cognitive components of the
      somatosensory evoked potential.
AB  - The question of interaction between ongoing neuronal activity and evoked
      responses has been addressed for different species, sensory systems and
      measurement modalities. Among other findings, there is converging evidence for an
      interaction of occipital alpha-rhythm amplitude with the visual evoked potential.
      Here, we test the hypothesis that the modulatory role of an ongoing rhythm might
      not be confined to the visual system and the occipital alpha rhythm, but instead
      may be generalized to other sensory systems. Using an online EEG analysis
      approach, we investigated the influence of the Rolandic alpha-rhythm on the
      somatosensory evoked potential (SEP). We triggered vibrotactile stimulation
      during periods of high Rolandic alpha-rhythm amplitude. Analysis revealed
      significant effects of pre-stimulus Rolandic alpha amplitude on the amplitude of
      the N140 and P260 components of the SEP, known to be linked to cognitive
      processing, but not on early sensory components. The N140-P260 complex shows a
      different focus in topography than the early sensory components and the pre
      stimulus Rolandic alpha rhythm. These results indicate an involvement of Rolandic
      alpha-rhythm in higher cognitive processing. In more general terms--and in the
      context of similar studies in the visual system--our findings suggest that
      modulation of late EP components by ongoing rhythms might be a characteristic and
      possibly universal feature of sensory systems.

PMID- 19589357
TI  - Immune responses induced by a BacMam virus expressing the E2 protein of classical
      swine fever virus in mice.
AB  - Non-replicating baculovirus-mediated gene transfer into mammalian cells has been
      developed as a vaccine strategy against a number of diseases in several animal
      models. In the present study, the BacMam vector, a baculovirus pseudotyped with
      the glycoprotein from vesicular stomatitis virus, was used as a recombinant
      vector to express classical swine fever virus (CSFV) E2 protein under the control
      of the immediate early 1 (ie1) promoter from shrimp white spot syndrome virus.
      The E2 gene was efficiently expressed in both insect and mammalian cells.
      Intramuscular injection of mice with the recombinant baculovirus resulted in the
      production of high-titers of CSFV-specific neutralizing antibodies. Specific
      lymphoproliferative responses to CSFV stimulation were detected in the
      splenocytes of the immunized mice as demonstrated by CFSE staining assay and WST
      8 assay. This study demonstrates that the BacMam virus vector can efficiently
      express the E2 protein and effectively induce immune responses against CSFV. This
      is a first step in the demonstration that the pseudotyped baculovirus-delivered
      CSFV E2 gene can be a potential non-replicating vaccine against CSFV infections.

PMID- 19589358
TI  - Identification of allosteric inhibitors blocking the hepatitis C virus polymerase
      NS5B in the RNA synthesis initiation step.
AB  - Hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B constitutes a target of
      choice for the development of anti-HCV drugs. Although many small molecules have
      been identified as allosteric inhibitors of NS5B, very few are active in clinical
      applications. We have screened 17,000 compounds in an enzymatic assay involving
      the purified NS5B in order to increase the therapeutic arsenal. We hoped to shed
      some light on the precise mechanism of RNA synthesis. We succeeded in isolating a
      series of 21 original inhibitors of the RNA synthesis by NS5B. Four of these non
      nucleoside inhibitors (NNIs) could be mapped to the known binding site called 'B'
      as judged by the decrease in their inhibition potency when assayed with a 'B'
      site mutant, M423T NS5B. Incidentally, our in silico model pointed to Y477 as a
      key residue for inhibitor binding. In vitro, Y477F mutant loses its sensitivity
      to the newly discovered inhibitors but is unable to extend primers during the
      elongation phase. Our results demonstrate that elements of the 'B' site are
      involved in the conformational changes required in the switch between the
      different RNA synthesis steps and that compounds targeting this site could lock
      the enzyme in its initiation phase.

PMID- 19589359
TI  - Effects of chronic intracerebroventricular 3,4-methylenedioxy-N-methamphetamine
      (MDMA) or fluoxetine on the active avoidance test in rats with or without
      exposure to mild chronic stress.
AB  - In despite the similarity of mechanisms of action between both selective
      serotonin reuptake inhibitors (SSRI) and MDMA (main compound of "Ecstasy") there
      are relatively few reports on the effects of the later on animal models of
      depression. There are many animal models designed to create or to assess
      depression. Mild chronic stress (MCS) is a procedure designed to create
      depression. MCS includes the chronic exposure of the animal to several stressors.
      After that, rats show behavioural changes associated to depression. In the other
      hand, the active avoidance task (AAT) is an experimental situation in which an
      animal has to accomplish a particular behaviour in order to avoid the application
      of a stressor. Animals exhibiting depression fail to acquire avoidance responses
      as rapidly as normal animals do. In order to assess the effect of MDMA on the
      acquisition of an active avoidance response, forty-five rats were divided in two
      groups exposed or not exposed to MCS. Rats also received chronic
      intracerebroventricular MDMA (0.2microg/microl; 1microl), fluoxetine
      (2.0microg/microl; 1microl) or saline solution (0.9%; 1microl). Our results
      showed that the effect of MDMA depends upon the level of stress. MDMA treated
      animals showed better acquisition (F([2,37])=7.046; P=0.003) and retention
      (F([2,37])=3.900; P=0.029) of the avoidance response than fluoxetine or saline
      treated animals when exposed to MCS. This finding suggests that MDMA (and no
      fluoxetine) was able to change the aversive valence of the stressors maybe
      enhancing coping strategies. This effect could serve as a protective factor
      against helplessness and maybe post-traumatic stress.

PMID- 19589360
TI  - Formin-binding proteins: modulators of formin-dependent actin polymerization.
AB  - Formins represent a major branch of actin nucleators along with the Arp2/3
      complex, Spire and Cordon-bleu. Formin-mediated actin nucleation requires the
      formin homology 2 domain and, although the nucleation per se does not require
      additional factors, formin-binding proteins have been shown to be essential for
      the regulation of formin-dependent actin assembly in vivo. This regulation could
      be accomplished by formin-binding proteins being directly involved in formin
      driven actin nucleation, by formin-binding proteins influencing the activated
      state of the formins, by linking formin-driven actin polymerization to Arp2/3
      driven actin polymerization, or by influencing the subcellular localization of
      the formins. This review article will focus on mammalian formin-binding proteins
      and their roles during vital cellular processes, such as cell migration, cell
      division and intracellular trafficking.

PMID- 19589361
TI  - Chewing gum does not induce context-dependent memory when flavor is held
      constant.
AB  - This study examined the effect of chewing gum on memory when flavor is held
      constant. Four separate groups of participants (total n=101) completed a word
      recall task. At learning and recall, participants either chewed a piece of gum or
      sucked a sweet. Each participant completed the memory task twice, once with
      abstract words and once with concrete words. A significant effect of word type
      (concrete vs. abstract) was found, however recall performance was not improved by
      matched oral activity at learning and recall. The results cast further doubt on
      the ability of chewing gum to induce context-dependent memory effects.

PMID- 19589363
TI  - Killer cell immunoglobulin-like receptor allele discrimination by high-resolution
      melting.
AB  - New molecular techniques for allele discrimination such as high-resolution
      melting (HRM) allow fast, reliable and high-throughput typing without the use of
      oligonucleotide probes. HRM can also provide an alternative for problematic
      allele assignments caused by the presence of homopolymeric regions or ambiguous
      haplotyping. We show here how we have used HRM to introduce upgrades in our KIR
      allele level typing system for the KIR2DS4, KIR2DL4, and KIR3DL2 genes. The
      allele assignments obtained by HRM, confirmed by sequencing, were clear-cut and
      reproducible. This technique allowed for quick and easy upgrading of the KIR
      allele frequencies and is now validated for future updates of KIR typing. The
      ongoing refinement of KIR haplotype distribution in our control population will
      help in disease association studies involving the KIR genes.

PMID- 19589362
TI  - Cathepsin L plays a major role in cholecystokinin production in mouse brain
      cortex and in pituitary AtT-20 cells: protease gene knockout and inhibitor
      studies.
AB  - Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires
      proteolytic processing of the proCCK precursor to generate active CCK8
      neuropeptide in brain. This study demonstrates the significant role of the
      cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO)
      mice, CCK8 levels were substantially reduced in brain cortex by an average of
      75%. To evaluate the role of cathepsin L in producing CCK in the regulated
      secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably
      produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK
      148 inhibitor treatment resulted in decreased amounts of CCK secreted from the
      regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular
      levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of
      cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK9/CCK8
      ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition
      of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the
      ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway
      for the production of CCK9. The changes in ratios of CCK9 compared to CCK8 are
      consistent with dual roles of the cathepsin L protease pathway that includes
      aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease
      pathway. These results suggest that cathepsin L functions as a major protease
      responsible for CCK8 production in mouse brain cortex, and participates with
      PC1/3 for CCK8 production in pituitary cells.

PMID- 19589364
TI  - Apoptosis differs in dendritic cell subsets early after severe trauma.
AB  - Dendritic cells (DC) represent an integral part of the immune system. However it
      is unclear how apoptosis in myeloid DC (MDC) and plasmacytoid DC (PDC) is
      affected and whether pro- or antiapoptotic properties dominate during the early
      post-traumatic phase. Blood samples were obtained on day 1 and day 4 after
      hospital admission from 10 severely traumatized patients and 10 healthy
      volunteers. Mononucleated cells were isolated and incubated with LPS. Apoptosis
      of MDC and PDC was assessed by annexin-V staining using flow cytometry.
      Expression of genes involved in apoptosis (Caspase-8, Flice inhibitory protein
      [FLIP], Bcl-2, Bax, Gadd45) in DC was measured by reverse transcriptase
      polymerase chain reaction. For statistical evaluation, the Kruskal-Wallis test
      was used (p < 0.05). Severe trauma increased apoptotic MDC compared with those in
      healthy controls (p < 0.05), whereas apoptosis of PDC was not influenced by the
      trauma impact. LPS stimulation decreased MDC apoptosis until day 4 after trauma;
      by contrast, for PDCs this effect was present only on day 1 after trauma. The Bcl
      2/Bax ratio in DCs increased significantly. We conclude that peripheral MDCs are
      more susceptible to undergo apoptosis after trauma compared with PDCs. However,
      the overall response of DCs early after trauma is characterized by an increased
      activation of antiapoptotic mediators that might indicate a compensatory life
      prolonging reaction.

PMID- 19589365
TI  - Non-clinical Post-Marketing Commitments for newly licenced pharmaceuticals.
AB  - There are clear minimum requirements for non-clinical (toxicology) studies which
      are needed prior to human exposure to a potential new pharmaceutical and
      additional studies are needed in an ongoing manner to support clinical
      development and marketing [ICH, 2009. ICH M3(R2) Non-clinical safety studies for
      the conduct of human clinical trials and marketing authorization for
      pharmaceuticals (CPMP/ICH/286/95). Adopted June 2009, effective December 2009.]
      The pharmaceutical industry is under increasing pressure to reduce costs and
      reduce, refine and replace the use of animals, as far as possible. Hence any
      increase in regulatory requirements for non-clinical safety data could have a
      significant impact both on the economic and ethical considerations of drug
      development. It is, therefore, of interest that further non-clinical studies are
      required by the Regulatory Authorities for a small but increasing proportion of
      drug product applications at the marketing approval/data review stage. These
      studies are known as Post-Marketing Commitments (PMCs). Available information on
      non-clinical PMCs was collated using drug product information from the US Food
      and Drug Administration (FDA) and the European Medicines Agency (EMEA), resulting
      in a combined data set of 162 studies. Non-clinical PMCs comprised 9.8% and 6.5%
      of total PMCs for products authorised by the EMEA (Centralised Procedure) and
      FDA, respectively. Non-clinical PMCs increased with increasing date of approval,
      despite increased regulatory information available to guide Applicants.
      Furthermore, the increase reflected an increased proportion of applications with
      non-clinical PMCs, not an increase in overall numbers of applications. There was
      no clear correspondence between the publication dates of relevant guidelines and
      increases in specific non-clinical PMC study types, when the data were analysed
      by non-clinical study category, target population/indication or compound class.
      Possible exceptions were some photocarcinogenicity and juvenile toxicity studies.
      For many non-clinical PMCs relevant guidance existed in the concurrent regulatory
      information. Hence these PMCs could have been predicted based on known
      pharmacology, indication and route/duration of administration. Conclusion. Some
      increases in non-clinical PMCs were attributed to increased non-clinical data
      requirements from the Regulators. However, strategic deferrals by the Applicant,
      unintended omissions due to poor regulatory intelligence and overall differences
      in risk perception between Regulators and Applicants account for a significant
      proportion of the non-clinical PMCs.

PMID- 19589366
TI  - Comparison of the nutritional-toxicological conflict related to seafood
      consumption in different regions worldwide.
AB  - This article discusses the seafood consumption worldwide as well as the related
      nutritional-toxicological conflict. An exposure assessment was performed using
      seafood consumption data from the Global Environment Monitoring System and
      nutrient and contaminant concentration data. The data indicated that the region
      of Japan, Korea, Madagascar and Philippines have the highest seafood consumption,
      followed by the Nordic-Baltic countries and South-East Asia. In Japan, Korea,
      Madagascar, Philippines and the Nordic-Baltic countries, pelagic marine fishes
      are highly consumed compared to fresh water fishes in South-East Asia. Because
      pelagic fishes are oily fishes, Japan, Korea, Madagascar, Philippines and the
      Nordic-Baltic countries have high omega-3 fatty acids and vitamin D intake.
      Iodine intake is influenced by the demersal fish consumption. The current intake
      of these nutrients via seafood consumption is still below the recommendations.
      From the toxicological side, the data indicate that none of the seafood groups
      had a median contaminant concentration above the EU maximum limits. Though, the
      results show that in some regions the contaminant intake exceeded the
      international health-based guidance values, mainly focussing on sensitive
      subpopulations. In contrast, when using less stringent guidance values relevant
      for non-sensitive subpopulations, the results show that the benefits of increased
      seafood consumption outweigh the risks.

PMID- 19589367
TI  - Mouse specific lung tumors from CYP2F2-mediated cytotoxic metabolism: an
      endpoint/toxic response where data from multiple chemicals converge to support a
      mode of action.
AB  - It is proposed that metabolism of several structurally-related chemicals by CYP2F
      isoforms of the cytochromes P450 family results in a cytotoxicity-driven mode of
      action in organs high in CYP2F; namely, CYP2F2 in nasal and lung tissue in mice
      and CYP2F4 in nasal tissues in rats. Importantly, the CYP2F1 isozyme expressed in
      humans appears to have a low capacity to metabolize these compounds. In mice, the
      resultant cytotoxicity and subsequent regenerative hyperplasia is hypothesized
      drive an increase in lung tumors that are mostly benign and are not life
      shortening. Although a complete picture of the mode of action has not been
      developed in any one model compound, data from the individual compounds can be
      combined to synthesize and reinforce confidence in the CYP2F toxicity hypothesis.
      For coumarin, naphthalene, and styrene, inhibition of toxicity with inhibition of
      CYP2F2 has been demonstrated. Rat CYP2F4 appears to be equally active in
      metabolizing these chemicals; however, CYP2F4 occurs to a much lower extent in
      rat Clara cells and levels of metabolites produced are not sufficient to cause
      lung cytotoxicity. Human lungs contain far fewer of Clara cells than rats or
      mice, and human lung microsomes failed to, or only marginally, metabolize these
      compounds. In addition, the human lung differs markedly from the mouse lung in
      the morphology of its Clara cells, which make humans much less sensitive than
      mice to toxicity due to reactive metabolites. The absence of a role for CYP2E1
      generated metabolites (primarily alkyl oxidation vs. ring-oxidation) in mouse
      pulmonary effects was demonstrated by the lack of protection from styrene
      toxicity by CYP2E1 inhibitor, or reduction of toxicity in CYP2E1-knockout mice,
      and lack of lung toxicity of the primary metabolite of ethylbenzene. The
      chemicals used as examples of this mode of action generally are negative in
      standard genotoxicity assays. Apart from increased SCE, no consistent pattern in
      genotoxicity results was found among these chemicals. Thus, while lung tumors
      from bronchiolar cell cytotoxicity are theoretically possible in humans, it is
      unlikely that metabolism by CYP2F1 would produce levels of cytotoxic metabolites
      in human lungs sufficient to result in lung cytotoxic responses and thus tumors.
      Therefore, it is unlikely several chemicals that cause mouse lung tumors via
      CYP2F2 metabolism will cause lung tumors in humans.

PMID- 19589369
TI  - RhoE is spatiotemporally regulated in the postnatal mouse CNS.
AB  - Rnd proteins are a family of small GTPases that have been involved in axon path
      finding and CNS development by their control of actin cytoskeleton dynamics. Rnd
      proteins are constitutively activated and, subsequently, their functions
      determined by their localization and expression levels. In this work we have
      analyzed by Western blot and immunohistochemistry the levels and localization of
      Rnd3/RhoE during mouse postnatal development. CNS was found to be the main tissue
      for RhoE protein expression, which was detected in all regions of the adult brain
      and spinal cord, with the highest levels in the olfactory bulb and cortex. RhoE
      protein levels were considerably higher in all the regions of the CNS the first 2
      3 weeks of postnatal development, undergoing later a decrease that led to low
      levels in the adult. Immunohistochemical detection of RhoE at postnatal day 21
      showed an intense and widespread labelling throughout the CNS. RhoE
      immunoreactivity was detected in the granular and mitral cells and anterior
      olfactory nuclei of the olfactory bulb and in all cerebral layers. In the
      striatum, diencephalon, mesencephalon, pons, medulla oblongata and spinal cord,
      RhoE was widely distributed with higher intensity in the motoneurones and in some
      brainstem nuclei such as the red nucleus or the reticulotegmental nucleus. The
      pyramidal cells of CA1-3 and the polymorph layer, but not the granular cells of
      the dentate gyrus in the hippocampus were strongly labelled. At earlier stages
      the labelling was nearly similar; however, a prominent labelling was detected in
      the cells of the rostral migratory stream and in the external granule cells of
      the cerebellum. Our results suggest that RhoE can play important roles in the
      postnatal development and maturation of the CNS, especially in the migratory
      processes affecting the neurones.

PMID- 19589368
TI  - Anxiogenic modulation of spontaneous and evoked neuronal activity in the
      basolateral amygdala.
AB  - The amygdala has a well-established role in stress, anxiety, and aversive
      learning, and anxiolytic and anxiogenic agents are thought to exert their
      behavioral actions via the amygdala. However, despite extensive behavioral data,
      the effects of noradrenergic anxiogenic drugs on neuronal activity within the
      amygdala have not been examined. The present experiments examined how
      administration of the anxiogenic drug yohimbine affects spontaneous and evoked
      neuronal activity in the basolateral amygdala (BLA) of rats. Yohimbine produced
      both excitatory and inhibitory effects on neurons of the BLA, with an increase in
      spontaneous activity being the predominant response in the lateral and basomedial
      nuclei of the BLA. Furthermore, yohimbine tended to facilitate neuronal responses
      evoked by electrical stimulation of the entorhinal cortex, with this facilitation
      seen more often in lateral and basomedial nuclei of the BLA. These data are the
      first to examine the effects of the anxiogenic agent yohimbine on BLA neuronal
      activity, and suggest that neurons in specific subnuclei of the amygdala exhibit
      unique responses to administration of such pharmacological agents.

PMID- 19589370
TI  - Ivane S. Beritashvili (1884-1974): from spinal cord reflexes to image-driven
      behavior.
AB  - Ivane Beritashvili ("Beritoff" in Russian, and often in Western languages) was a
      major figure in 20th-century neuroscience. Mastering the string galvanometer, he
      founded the electrophysiology of spinal cord reflexes, showing that inhibition is
      a distinctly different process from excitation, contrary to the concepts of his
      famous mentor, Wedensky. Work on postural reflexes with Magnus was cut short by
      World War I, but he later demonstrated that navigation in two-dimensional space
      without vision is a function solely of the vestibular system rather than of
      muscle proprioception. Persevering in his experiments despite postwar turmoil he
      founded an enduring Physiology Institute in Tbilisi, where he pursued an
      ingenious and extensive investigation of comparative memory in vertebrates. This
      revealed the unique nature of mammalian memory processes, which he forthrightly
      called "image driven," and distinguished them unequivocally from those underlying
      conditional reflexes. For some 30 years the Stalinist terror confined his
      publications to the Russian language. Work with his colleague, Chichinadze,
      discovering that memory confined to one cerebral hemisphere could be accessed by
      the other via a specific forebrain commissure, did reach the West, and ultimately
      led to recognition of the fascinating "split brain" condition. In the 1950s he
      was removed from his professorial position for 5 years as being "anti-Pavlovian."
      Restored to favor, he was honorary president of the "Moscow Colloquium" that saw
      the foundation of the International Brain Research Organization.

PMID- 19589371
TI  - Enriched environment promotes efficiency of compensatory movements after cerebral
      ischemia in rats.
AB  - Rehabilitation therapy is known to drive motor improvement in stroke patients.
      However, the interplay of functional recovery and compensation in postischemic
      motor behavior is poorly understood. This study focused on the time course of
      functional recovery versus motor compensation in skilled forelimb movements after
      cerebral ischemia in rats. Young adult male rats underwent a focal cerebral
      ischemia by unilateral photothrombotic lesion of the motor cortex related to the
      preferred forelimb. In a first set of experiments animals were exposed to small
      cortical lesions comprising the forelimb motor cortex (n=8) or to larger lesions
      additionally extending into the hind limb motor area (n=8). In a second set of
      experiments animals with large lesion were either housed in standard (n=10) or
      enriched environment (n=14). Skilled reaching was assessed for 25 to 28 days
      postischemia. This task allows the distinction between recovery and compensation
      by parallel quantitative (reaching success) and qualitative (movement pattern)
      analysis. The results reveal that lesion size determines the initial magnitude of
      motor deficits, but not the degree of chronic impairments in movement pattern in
      all experimental groups. Compensatory movements represent the major mechanism of
      functional improvement and were accompanied by a partial functional restitution.
      Enriched environment facilitates effective compensation in skilled reaching,
      while it does not promote restitution of function. In particular, rotating
      movements of the forelimb during reaching were permanently impaired and required
      functional compensation through intensified use of the upper body. We conclude an
      activity dependent postischemic restoration of movement success. Enriched
      environment provides benefit by increased motor activity mainly due to
      compensation. Furthermore, these findings emphasize the power of comprehensive
      movement analysis to gain insight into recovery processes after stroke.

PMID- 19589372
TI  - Characterization of green fluorescent protein-expressing retinal cone bipolar
      cells in a 5-hydroxytryptamine receptor 2a transgenic mouse line.
AB  - Retinal bipolar cells relay visual information from photoreceptors to third-order
      retinal neurons. Bipolar cells, comprising multiple types, play an essential role
      in segregating visual information into multiple parallel pathways in the retina.
      The identification of molecular markers that can label specific retinal bipolar
      cells could facilitate the investigation of bipolar cell functions in the retina.
      Transgenic mice with specific cell type(s) labeled with green fluorescent protein
      (GFP) have become a powerful tool for morphological and functional studies of
      neurons in the CNS, including the retina. In this study, we report a 5
      hydroxytryptamine receptor 2a (5-HTR2a) transgenic mouse line in which expression
      of GFP was observed in two populations of bipolar cells in the retina. Based on
      the terminal stratification and immunostaining, all the strongly GFP-labeled
      bipolar cells were found to be type 4 cone bipolar cells. A small population of
      weakly labeled bipolar cells was also observed, which may represent type 8 or 9
      cone bipolar cells. GFP expression in retinal cone bipolar cells was seen as
      early as postnatal day 5. In addition, despite severe retinal degeneration due to
      the presence of the rd1 mutation in this transgenic line, the density of GFP
      labeled cone bipolar cells remained stable up to at least 6 months of age. This
      transgenic mouse line will be a useful tool for the study of type 4 cone bipolar
      cells in the retina under both normal and disease conditions.

PMID- 19589373
TI  - The effect of depression, BDNF gene val66met polymorphism and gender on serum
      BDNF levels.
AB  - OBJECTIVE: To determine the effect of BDNF gene val66met polymorphism on serum
      BDNF levels in drug-free patients with major depressive disorder (MDD) and
      healthy subjects, that differ by gender. METHODS: Sixty-six drug-free patients
      (19 males+47 females) with non-psychotic MDD and fifty-six healthy controls (18
      males+38 females) were recruited. Three-way ANOVA was employed to analyze the
      effect of mental health status, met-carriage and gender on Hamilton Depression
      Rating Scale (HDRS) scores and serum BDNF levels, by using the MIXED Procedure
      (SAS). RESULTS: Patients had a lower serum BDNF level than healthy subjects
      (22.47 vs. 27.49; p<0.0001). Met-carrier patients had a higher HDRS score than
      Val homozygote's (25.99 vs. 22.99, p<0.02). Serum BDNF level for met-carrier
      subjects (patients+controls) was lower than Val homozygote subjects (23.08 vs.
      26.87; p<0.002). However, there were no effects of two-way interactions of met
      carriage and mental health status on HDRS scores and serum BDNF levels. There was
      no gender effect on HDRS scores in the patients. Overall, male subjects
      (patients+controls) had a higher serum BDNF level than female subjects (26.87 vs.
      23.08; p<0.002). However, there were no effects of two-way interactions of gender
      with mental health status and met-carriage on serum BDNF levels. CONCLUSIONS: We
      replicated the previous findings of lower serum BDNF levels during depression and
      in females. In addition, we found that met-carriage had an effect in reducing
      serum BDNF levels, regardless of gender and depression. Further animal and human
      studies with a larger sample size should investigate whether BDNF val66met
      polymorphism could alter brain and serum BDNF levels.

PMID- 19589374
TI  - Regional cerebral blood flow increases during wakeful rest following cognitive
      training.
AB  - Positron tomography was used to investigate modulations of brain activity during
      the so-called resting state that may occur due to a concurrent cognitive
      training. Twelve subjects were repeatedly scanned during resting periods and
      while solving logical problems containing a bias causing them to make reasoning
      errors. At experiment mid-time, eight subjects were trained to inhibit the
      reasoning bias so that their performance in solving logical problems dramatically
      increased afterwards, while the other four subjects were trained to logical
      reasoning only which did not help improving their performance. In the subgroup of
      subjects who increased their performance after training, we found that during the
      post-training resting periods, as compared to pre-training resting periods, brain
      activity increases in areas not belonging to the classical resting network,
      namely the midbrain, thalamus, peristriate, inferior frontal, and ventromedial
      prefrontal cortices. Strikingly, in this subgroup of subjects, these same areas
      were found to be also more active during post-training successful execution of
      the logical task, as compared to pre-training erroneous execution of the task.
      Such findings were not observed in the subgroup of subjects who did not improve
      their performance after training to logic only. These results indicate that the
      brain default mode is a dynamic state during which context dependent local
      increases of cerebral blood flow may occur on a short-term, likely for the
      consolidation of newly acquired knowledge.

PMID- 19589376
TI  - Nanovesicles released by Dictyostelium cells: a potential carrier for drug
      delivery.
AB  - Nanovesicles released by Dictyostelium discoideum cells grown in the presence of
      the DNA-specific dye Hoechst 33342 have been previously shown to mediate the
      transfer of the dye into the nuclei of Hoechst-resistant cells. The present
      investigation extends this work by conducting experiments in the presence of
      hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral
      photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an
      averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron
      microscopy. A proteomic analysis reveals a predominance of actin and actin
      related proteins. The detection of a lysosomal membrane protein (LIMP II)
      indicates that these vesicles are likely generated in the late endosomal
      compartment. The use of the hypericin-containing nanovesicles as nanodevices for
      in vitro drug delivery was investigated by fluorescence microscopy. The observed
      signal was almost exclusively located in the perinuclear area of two human cell
      lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by
      confocal microscopy with specific markers of cell organelles, provided evidence
      that hypericin was accumulated in the Golgi apparatus. All these data shed a new
      light on in vitro drug delivery by using cell-released vesicles as carriers.

PMID- 19589378
TI  - An observational study on the influence of solvent composition on the
      architecture of drug-layered pellets.
AB  - Pelletization for the manufacture of modified release multiparticulate drug
      delivery systems is often considered to be well defined and robust. However,
      small differences in formulation conditions can lead to surprising changes to the
      expected outcomes. We observed that extended release tramadol hydrochloride
      pellets, prepared by solution layering an ethanolic solution of drug on a non
      pareil, resulted in highly unusual pellet architecture with deep indentations
      which prevented the application of a homogeneous outer coating of ethylcellulose
      and talc, and negatively influenced the desired modified release characteristics.
      Modification of outer coating thickness and process temperature showed no
      improvement in release characteristics. A solution to the problem was found in
      the incorporation of 10% v/v water into the ethanolic drug layering solution,
      resulting in the production of drug-loaded pellets with a smooth morphology which
      allowed the application of a coherent outer coating able to retard drug release.
      The surprising difference in pellet morphology between the two solvent drug
      layering systems may be attributed to differences in solvent evaporation rates.
      This demonstrates that established techniques are sometimes less straightforward
      than thought as small changes in formulation have significant effects on the
      resulting product in a way which is not always well understood.

PMID- 19589377
TI  - Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous
      delivery of minoxidil.
AB  - The aim of this work was to evaluate the ability of a few different penetration
      enhancers to produce elastic vesicles with soy lecithin and the influence of the
      obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this
      purpose, so-called Penetration Enhancer-containing Vesicles (PEVs) were prepared
      as dehydrated-rehydrated vesicles by using soy lecithin and different amounts of
      three penetration enhancers, 2-(2-ethoxyethoxy)ethanol (Transcutol), capryl
      caproyl macrogol 8-glyceride (Labrasol), and cineole. Soy lecithin liposomes,
      without penetration enhancers, were used as control. Prepared formulations were
      characterized in terms of size distribution, morphology, zeta potential, and
      vesicle deformability. The influence of PEVs on (trans)dermal delivery of
      minoxidil was studied by in vitro diffusion experiments through newborn pig skin
      in comparison with traditional liposomes and ethanolic solutions of the drug also
      containing each penetration enhancer. A skin pre-treatment study using empty PEVs
      and conventional liposomes was also carried out. Results showed that all the used
      penetration enhancers were able to give more deformable vesicles than
      conventional liposomes with a good drug entrapment efficiency and stability. In
      vitro skin penetration data showed that PEVs were able to give a statistically
      significant improvement of minoxidil deposition in the skin in comparison with
      classic liposomes and penetration enhancer-containing drug ethanolic solutions
      without any transdermal delivery. Moreover, the most deformable PEVs, prepared
      with Labrasol and cineole, were also able to deliver to the skin a higher total
      amount of minoxidil than the PE alcoholic solutions thus suggesting that
      minoxidil delivery to the skin was strictly correlated to vesicle deformability,
      and therefore to vesicle composition.

PMID- 19589379
TI  - Expression of the neural specific protein, GAP-43, dramatically lengthens the
      cell cycle in fibroblasts.
AB  - It has been demonstrated that during neurogenesis in the mammalian brain, cell
      cycle lengthening in neuronal progenitors may cause them to switch from
      proliferation to neuron-generating division. However, little is known about the
      cellular mechanisms involved in lengthening of the cell cycle. Growth-associated
      protein-43 (GAP-43) is a nervous system-specific protein whose expression in
      proliferating neuroblasts is related to neurogenesis. In this study, we
      investigated the effect of GAP-43 on cell-cycle progression in transgenic
      fibroblast cells. Using cumulative bromodeoxyuridine labeling, cell-cycle
      kinetics in GAP-43-transgenic and control NIH 3T3 cells were analyzed. Our data
      demonstrate that expression of GAP-43 in fibroblasts results in lengthening of
      the cell cycle compared to control fibroblasts. The mechanism by which GAP-43
      mediated this effect appeared to involve increasing the time spent by the cells
      in the G(1) phase of the cell cycle.

PMID- 19589380
TI  - Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor
      protein and beta-amyloidogenesis in brain slice cultures derived from transgenic
      Tg2576 mouse brain.
AB  - The up-regulation of the angiogenic vascular endothelial growth factor (VEGF) in
      brains of Alzheimer patients in close relationship to beta-amyloid (Abeta)
      plaques, suggests a link of VEGF action and processing of the amyloid precursor
      protein (APP). To reveal whether VEGF may affect APP processing, brain slices
      derived from 17-month-old transgenic Tg2576 mice were exposed with 1ng/ml VEGF
      for 6, 24, and 72h, followed by assessing cytosolic and membrane-bound APP
      expression, level of both soluble and fibrillar Abeta-peptides, as well as
      activities of alpha- and beta-secretases in brain slice tissue preparations.
      Treatment of brain slices with VEGF did not significantly affect the expression
      level of APP, regardless of the exposure time studied. In contrast, VEGF exposure
      of brain slices for 6h reduced the formation of soluble, SDS extractable Abeta(1
      40) and Abeta(1-42) as compared to brain slice cultures incubated in the absence
      of any drug, while the fibrillar Abeta peptides did not change significantly.
      This effect was less pronounced 24h after VEGF exposure, but was no longer
      detectable when brain slices were exposed by VEGF for 72h, which indicates an
      adaptive response to chronic VEGF exposure. The VEGF-mediated reduction in Abeta
      formation was accompanied by a transient decrease in beta-secretase activity
      peaking 6h after VEGF exposure. To reveal whether the VEGF-induced changes in
      soluble Abeta-level may be due to actions of VEGF on Abeta fibrillogenesis, the
      fibrillar status of Abeta was examined using the thioflavin-T binding assay.
      Incubation of Abeta preparations obtained from Tg2576 mouse brain cortex, in the
      presence of VEGF slightly decreased the fibrillar content with increasing
      incubation time up to 72h. The data demonstrate that VEGF may affect APP
      processing, at least in vitro, suggesting a role of VEGF in the pathogenesis of
      Alzheimer's disease.

PMID- 19589381
TI  - Fos immunoreactivity in the rat forebrain induced by electrical stimulation of
      the dorsolateral periaqueductal gray matter.
AB  - Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) matter
      induces panic- or fear-like responses with intense emotional distress and severe
      anxiety. In this study, we evoked panic-like behaviour by dlPAG stimulation and
      evaluated the effect on neuronal activation in different brain regions. The
      number of c-Fos immunoreactive (c-Fos-ir) cells was measured semi-quantitatively
      through series of stained rat brain sections. Our results demonstrate strong
      neural activation in the medial prefrontal cortex, orbital cortex, anterior
      olfactory nuclei, secondary motor cortex, and the somatosensory cortex. Moderate
      increases in the number of c-Fos-ir cells were detected in various regions,
      including the hypothalamus, amygdala, and striatum. Additionally, there was mild
      expression of c-Fos-ir cells in the hippocampus, thalamus, and habenula regions.
      In conclusion, we have shown that deep brain stimulation of the dlPAG produced a
      distinctive pattern of neuronal activation across forebrain regions as compared
      to the sham and control animals.

PMID- 19589383
TI  - Aromatic L-amino acid decarboxylase-immunoreactive structures in human midbrain,
      pons, and medulla.
AB  - The objective of the present study was to determine with precision the
      localization of neurons and fibers immunoreactive (ir) for aromatic L-amino acid
      decarboxylase (AADC), the second-step enzyme responsible for conversion of L
      dihydroxyphenylalanine (L-DOPA) to dopamine (DA) and 5-hydroxytryptophan (5-HTP)
      to serotonin (5-hydroxytryptamine: 5-HT) in the midbrain, pons, and medulla
      oblongata of the adult human brain. Intense AADC immunoreactivity was observed in
      a large number of presumptive 5-HT neuronal cell bodies distributed in all of the
      raphe nuclei, as well as in regions outside the raphe nuclei such as the ventral
      portions of the pons and medulla. Moderate to strong immunoreaction was
      observable in presumptive DA cells in the mesencephalic reticular formation,
      substantia nigra, and ventral tegmental area of Tsai, as well as in presumptive
      noradrenergic (NA) cells, which were aggregated in the locus coeruleus and
      dispersed in the subcoeruleus nuclei. In the medulla oblongata, immunoreaction of
      moderate intensity was distributed in the mid and ventrolateral portions of the
      intermediate reticular nucleus, which constitutes the oblique plate of A1/C1
      presumptive adrenergic and/or NA neurons. The dorsal vagal AADC-ir neurons were
      fewer in number and stained more weakly than cells immunoreactive for tyrosine
      hydroxylase (TH). AADC immunoreactivity was not identified in an aggregate of TH
      ir neurons lying in the gelatinous subnucleus of the solitary nucleus, a
      restricted region just rostroventral to the area postrema. Nonaminergic AADC
      positive neurons (D neurons), which are abundant in the rat and cat midbrain,
      pons, and medulla, were hardly detectable in homologous regions in the human
      brain, although they were clearly distinguishable in the forebrain.

PMID- 19589384
TI  - Choice of an adequate promoter for efficient complementation in Saccharomyces
      cerevisiae: a case study.
AB  - Conservation of the function of open reading frames recently identified in fungal
      genome projects can be assessed by complementation of deletion mutants of
      putative Saccharomyces cerevisiae orthologs. A parallel complementation assay
      expressing the homologous wild type S. cerevisiae gene is generally performed as
      a positive control. However, we and others have found that failure of
      complementation can occur in this case. We investigated the specific cases of S.
      cerevisiae TBF1 and TIM54 essential genes. Heterologous complementation with
      Candida glabrata TBF1 or TIM54 gene was successful using the constitutive
      promoters TDH3 and TEF. In contrast, homologous complementation with S.
      cerevisiae TBF1 or TIM54 genes failed using these promoters, and was successful
      only using the natural promoters of these genes. The reduced growth rate of S.
      cerevisiae complemented with C. glabrata TBF1 or TIM54 suggested a diminished
      functionality of the heterologous proteins compared to the homologous proteins.
      The requirement of the homologous gene for the natural promoter was alleviated
      for TBF1 when complementation was assayed in the absence of sporulation and
      germination, and for TIM54 when two regions of the protein presumably responsible
      for a unique translocation pathway of the TIM54 protein into the mitochondrial
      membrane were deleted. Our results demonstrate that the use of different
      promoters may prove necessary to obtain successful complementation, with use of
      the natural promoter being the best approach for homologous complementation.

PMID- 19589385
TI  - Defining the natural habitat of Bacillus spore-formers.
AB  - Our understanding of the genetics and physiology of the spore-forming genus
      Bacillus is remarkable. On the other hand, though, where these Gram-positive
      bacteria live and grow is far from clear. The soil, once considered their
      habitat, may simply serve as a reservoir. A growing number of studies show that
      Bacillus spores can be found in the intestinal tracts of animals, raising the
      question of whether this could be where they live and grow. In this study, we
      have conducted the first evaluation of Bacillus spore formers in soil and in
      human faeces. Our aim is simply to determine the abundance of aerobic spore
      formers. Our results show that soil carries approximately approximately
      10(6)spores/g while human faeces an average of up to 10(4)spores/g. The numbers
      of spores found in faeces, we reason, is too high to be accounted for principally
      by ingestion of food contaminated with spores from soil. This provides further
      evidence that Bacillus spore formers may have adapted to survival within the
      intestinal tract of insects and other animals that ingest them; if so they may
      well be hitherto undiscovered gut commensals.

PMID- 19589386
TI  - Screening Swiss water bodies for potentially pathogenic free-living amoebae.
AB  - Free-ling amoebae (FLA) including Acanthamoeba spp., Naegleria fowleri,
      Balamuthia mandrillaris and Sappinia pedata, can cause opportunistic infections
      leading to severe brain pathologies. Human infections with pathogenic FLA have
      been increasingly documented in many countries. In Switzerland, thus far, the
      occurrence and distribution of potentially pathogenic FLA has not been
      investigated. Swiss water biotopes, including swimming pools, lakes, rivers and
      ponds, have now been screened for the presence of FLA, and assessment of their
      pathogenicity potential for a mammalian host has been undertaken. Thus, a total
      of 17 isolates were recovered by in vitro cultivation from these different
      aquatic sources. Characterization by sequence analysis of Acanthamoeba spp.
      specific and 'FLA-specific PCR products amplified from 18s rDNA based on
      morphological traits, thermotolerance, and cytotoxicity towards murine
      fibroblasts yielded the following findings: Echinamoeba cf. exundans (3
      isolates), Hartmannella spp. (3), Vannella spp. (4), Protacanthamoebica cf.
      bohemica (1), Acanthamoeba cf. castellanii (1) and Naegleria spp. (5). B.
      mandrillaris and N. fowleri did not range amongst these isolates. None of the
      isolates exhibited pronounced cytotoxicity and all failed to grow at 42 degrees
      C; therefore, they do not present any potential for CNS pathogenicity for humans.

PMID- 19589382
TI  - Birdsong and the neural production of steroids.
AB  - The forebrain circuits involved in singing and audition (the 'song system') in
      songbirds exhibit a remarkable capacity to synthesize and respond to steroid
      hormones. This review considers how local brain steroid production impacts the
      development, sexual differentiation, and activity of song system circuitry. The
      songbird forebrain contains all of the enzymes necessary for the de novo
      synthesis of steroids - including neuroestrogens - from cholesterol. Steroid
      production enzymes are found in neuronal cell bodies, but they are also expressed
      in pre-synaptic terminals in the song system, indicating a novel mode of brain
      steroid delivery to local circuits. The song system expresses nuclear hormone
      receptors, consistent with local action of brain-derived steroids. Local steroid
      production also occurs in brain regions that do not express nuclear hormone
      receptors, suggesting a non-classical mode of action. Recent evidence indicates
      that local steroid levels can change rapidly within the forebrain, in a manner
      similar to traditional neuromodulators. Lastly, we consider growing evidence for
      modulatory interactions between brain-derived steroids and
      neurotransmitter/neuropeptide networks within the song system. Songbirds have
      therefore emerged as a rich and powerful model system to explore the neural and
      neurochemical regulation of social behavior.

PMID- 19589387
TI  - Purification of recombinant mandelate racemase: improved catalytic activity.
AB  - Mandelate racemase (MR, E.C. 5.1.2.2) from Pseudomonas putida catalyzes the
      Mg(2+)-dependent 1,1-proton transfer that interconverts the enantiomers of
      mandelate and has been studied extensively as a model for understanding how
      enzymes catalyze the deprotonation of carbon acid substrates with relatively high
      pK(a) values. Purification of recombinant MR as a fusion protein with an N
      terminal hexahistidine tag using immobilized-nickel ion affinity chromatography
      and elution with a linear gradient of EDTA revealed three enzyme species (mrI,
      mrII, and mrIII). While mrIII was catalytically inactive, both mrI and mrII
      catalyzed the racemization of (S)-mandelate with turnover numbers (k(cat)) of
      190+/-22 and 940+/-24s(-1), respectively. Circular dichroism analysis suggested
      that mrIII was a partially unfolded or misfolded form of the enzyme. Replacement
      of the N-terminal hexahistidine tag by a StrepII-tag appeared to ameliorate the
      folding problem yielding a single enzyme species with a turnover number of 1124+/
      43s(-1). The MR fusion protein bearing an N-terminal StrepII-tag and a C-terminal
      decahistidine tag also exhibited reduced turnover (k(cat)=472+/-37s(-1)). These
      results highlight a potential problem that may be encountered when producing
      fusion enzymes bearing a polyhistidine tag: soluble, active enzyme may be
      obtained but care must be taken to ensure that it is free of minor misfolded
      forms that can alter the apparent activity of the enzyme.

PMID- 19589389
TI  - Bayesian phylogeny analysis via stochastic approximation Monte Carlo.
AB  - Monte Carlo methods have received much attention in the recent literature of
      phylogeny analysis. However, the conventional Markov chain Monte Carlo
      algorithms, such as the Metropolis-Hastings algorithm, tend to get trapped in a
      local mode in simulating from the posterior distribution of phylogenetic trees,
      rendering the inference ineffective. In this paper, we apply an advanced Monte
      Carlo algorithm, the stochastic approximation Monte Carlo algorithm, to Bayesian
      phylogeny analysis. Our method is compared with two popular Bayesian phylogeny
      software, BAMBE and MrBayes, on simulated and real datasets. The numerical
      results indicate that our method outperforms BAMBE and MrBayes. Among the three
      methods, SAMC produces the consensus trees which have the highest similarity to
      the true trees, and the model parameter estimates which have the smallest mean
      square errors, but costs the least CPU time.

PMID- 19589388
TI  - Purkinje cell loss in experimental autoimmune encephalomyelitis.
AB  - Gray matter atrophy observed by brain MRI is an important correlate to clinical
      disability and disease duration in multiple sclerosis. The objective of this
      study was to link brain atrophy visualized by neuroimaging to its underlying
      neuropathology using the MS model, experimental autoimmune encephalomyelitis
      (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy
      normal controls, were quantified by collecting post-mortem high-resolution T2
      weighted magnetic resonance microscopy and actively stained magnetic resonance
      histology images. Anatomical delineations demonstrated a significant decrease in
      the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the
      cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker
      caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje
      cell number was found in EAE. Cross modality and temporal correlations revealed a
      significant association between Purkinje cell loss on neuropathology and atrophy
      of the molecular layer of the cerebellar cortex by neuroimaging. These results
      demonstrate the power of using combined population atlasing and neuropathology
      approaches to discern novel insights underlying gray matter atrophy in animal
      models of neurodegenerative disease.

PMID- 19589390
TI  - CJX1, an amlodipine derivative, interacts with ATPase of human P-glycoprotein.
AB  - Our aim has been to elucidate the possible mechanism of CJX1, an amlodipine
      derivative, in the modulation of P-gp function by determining its effect on P-gp
      ATPase activity. Basal P-gp ATPase activity was increased by CJX1 with half
      maximal activity concentration (Km) of 8.6+/-1.4 microM. Kinetic analysis
      indicated a non-competitive inhibition of Verapamil (Ver)-stimulated P-gp ATPase
      activity by CJX1 and competitive inhibition of CJX1-stimulated P-gp ATPase
      activity by tetrandrine (Tet). The effect of CsA on CJX1-stimulated and Ver
      stimulated P-gp ATPase activity was non-competitive and competitive inhibition,
      respectively. These findings implying that CJX1 and Tet can bind P-gp either on
      overlapping sites or distinct but interacting sites, while CJX1 and Ver as well
      as CsA can bind P-gp on separated sites in K562/DOX cells. Furthermore, the
      combined effect of CJX1 and Ver has been evaluated isobolographically in numerous
      fixed-ratio combinations of 1:1, 1:2, 1:4, 1:8, 1:10 in K562/DOX cells. The
      results show that mixtures of both drugs at these fixed-ratios exerted
      synergistic interactions, indicating that when the two reverses that bind P-gp on
      separated sites are combined, each can contribute to the overall interaction with
      P-gp, leading to the greater effect than that by either agent alone.

PMID- 19589391
TI  - Cell culturing in a three-dimensional matrix affects the localization and
      properties of plasma membrane cholesterol.
AB  - Most in vitro studies use 2-dimensional (2D) monolayer cultures, where cells are
      forced to adjust to unnatural substrates that differ significantly from the
      natural 3-dimensional (3D) extracellular matrix that surrounds cells in living
      organisms. Our analysis demonstrates significant differences in the cholesterol
      and sphingomyelin content, structural organization and cholesterol susceptibility
      to oxidation of plasma membranes isolated from cells cultured in 3D cultures
      compared with conventional 2D cultures. Differences occurred in the asymmetry of
      cholesterol molecules and the physico-chemical properties of the 2 separate
      leaflets of plasma membranes in 2D and 3D cultured fibroblasts. Transmembrane
      distribution of other membrane phospholipids was not different, implying that the
      cholesterol asymmetry could not be attributed to alterations in the scramblase
      transport system. Differences were also established in the chemical activity of
      cholesterol, assessed by its susceptibility to cholesterol oxidase in
      conventional and "matrix" cell cultures. The influence of plasma membrane
      sphingomyelin and phospholipid content on cholesterol susceptibility to oxidation
      in 2D and 3D cells was investigated with exogenous sphingomyelinase (SMase) and
      phospholipase C (PLC) treatment. Sphingomyelin was more effective than membrane
      phospholipids in protecting cholesterol from oxidation. We presume that the
      higher cholesterol/sphingomyelin molar ratio is the reason for the higher rate of
      cholesterol oxidation in plasma membranes of 3D cells.

PMID- 19589392
TI  - Cloning and characterization of novel methylsalicylic acid synthase gene involved
      in the biosynthesis of isoasperlactone and asperlactone in Aspergillus
      westerdijkiae.
AB  - Aspergillus westerdijkiae is the main producer of several biologically active
      polyketide metabolites including isoasperlactone and asperlactone. A 5298bp
      polyketide synthase gene "aomsas" has been cloned in Aspergillus westerdijkiae by
      using gene walking approach and RACE-PCR. The predicted amino acid sequence of
      aomsas shows an identity of 40-56% with different methylsalicylic acid synthase
      genes found in Byssochlamys nivea, P. patulum, A. terreus and Streptomyces
      viridochromogenes. Based on the reverse transcription PCR and kinetic secondary
      metabolites production studies, aomsas expression was found to be associated with
      the biosynthesis of isoasperlactone and asperlactone. Moreover an aomsas knockout
      mutant "aoDeltamsas" of A. westerdijkiae, not only lost the capacity to produce
      isoasperlactone and asperlactone, but also 6-methylsalicylic acid. The
      genetically complemented mutant ao+msas restored the biosynthesis of all the
      missing metabolites. Chemical complementation through the addition of 6
      methylsalicylic acid, aspyrone and diepoxide to growing culture of aoDeltamsas
      mutant revealed that these compounds play intermediate roles in the biosynthesis
      of asperlactone and isoasperlactone.

PMID- 19589393
TI  - Identification of the cellulose synthase genes from the Oomycete Saprolegnia
      monoica and effect of cellulose synthesis inhibitors on gene expression and
      enzyme activity.
AB  - Cellulose biosynthesis is a vital but yet poorly understood biochemical process
      in Oomycetes. Here, we report the identification and characterization of the
      cellulose synthase genes (CesA) from Saprolegnia monoica. Southern blot
      experiments revealed the occurrence of three CesA homologues in this species and
      phylogenetic analyses confirmed that Oomycete CesAs form a clade of their own.
      All gene products contained the D,D,D,QXXRW signature of most processive
      glycosyltransferases, including cellulose synthases. However, their N-terminal
      ends exhibited Oomycete-specific domains, i.e. Pleckstrin Homology domains, or
      conserved domains of an unknown function together with additional putative
      transmembrane domains. Mycelial growth was inhibited in the presence of the
      cellulose biosynthesis inhibitors 2,6-dichlorobenzonitrile or Congo Red. This
      inhibition was accompanied by a higher expression of all CesA genes in the
      mycelium and increased in vitro glucan synthase activities. Altogether, our data
      strongly suggest a direct involvement of the identified CesA genes in cellulose
      biosynthesis.

PMID- 19589394
TI  - Ontogenic change in tissue osmolality and developmental sequence of mitochondria
      rich cells in Mozambique tilapia developing in freshwater.
AB  - We investigated a change in tissue fluid osmolality and developmental sequences
      of mitochondria-rich (MR) cells during embryonic and larval stages of Mozambique
      tilapia, Oreochromis mossambicus, developing in freshwater. Tissue osmolality,
      representing body fluid osmolality, ranged from 300 to 370 mOsm/kg during
      embryonic and larval stages. This suggests that tilapia embryos and larvae are
      also able to regulate body fluid osmolality to some extent, although the levels
      are somewhat higher and fluctuate more greatly in embryos and larvae than in
      adults. Na(+)/K(+)-ATPase-immunoreactive MR cells were first detected in the yolk
      sac membrane 3 days before hatching (day -3), followed by their appearance in the
      body skin on day -2. Subsequently, MR cells in both the yolk-sac membrane and
      body skin increased in number, and most densely observed on days -1 and 0.
      Whereas yolk-sac and skin MR cells decreased after hatching, MR cells in turn
      started developing in the gills after hatching. Thus, the principal site for MR
      cell distribution shifted from the yolk-sac membrane and body skin during
      embryonic stages to the gills during larval stages, and tilapia could maintain
      continuously their ion balance through those MR cells during early life stages.

PMID- 19589395
TI  - No backbone but lots of Sox: Invertebrate Sox genes.
AB  - Sox transcription factors are intimately involved in the development of
      multicellular organisms and accordingly understanding the role Sox genes play in
      diverse species of metazoans will hopefully shed light on the evolution of
      multicellularity. Here we review our current knowledge of the Sox genes isolated
      and characterised in invertebrates, ranging from the very simplest organisms
      through to complex chordates. While Sox genes have been identified in many
      invertebrate species, comparatively little is known about their functions outside
      the well-studied models, Drosophila, sea urchin and nematode. Consequently, we
      centre this review around the Sox family in Drosophila, comparing this with what
      is known about orthologous genes in other invertebrate species. We highlight
      several conserved themes that emerge when looking at the roles Sox proteins
      appear to play during embryogenesis, including early functions in CNS development
      and widespread interactions with the Wnt signalling pathway. Comparing the
      expression of Sox genes in insect species, where genome organisation is conserved
      but expression is apparently not, highlights the need for more functional data on
      the roles that related Sox proteins play in organisms outside the well
      characterised models.

PMID- 19589397
TI  - Anti-angiogenic effect of caffeic acid on retinal neovascularization.
AB  - Pathological angiogenesis is the most common cause of vision loss at all ages
      including retinopathy of prematurity (ROP), diabetic retinopathy, and age-related
      macular degeneration. ROP is a proliferative disease of the retinal vasculature
      in premature infants. Herein, we demonstrated caffeic acid (CA) has the anti
      angiogenic activity to retinal endothelial cells and retinal neovascularization
      in a mouse model of ROP, which might be related to the suppression of ROS-induced
      VEGF expression. CA effectively inhibited VEGF-induced proliferation of retinal
      endothelial cells in concentration-dependent manner. In addition, VEGF-induced
      migration and tube formation of retinal endothelial cells were completely
      inhibited. This anti-angiogenic activity of CA on retinal endothelial cells was
      related to the anti-oxidant activity: the inhibitory activity of CA to H(2)O(2)
      induced reactive oxygen species production and VEGF expression. Interestingly, CA
      significantly suppressed retinal neovascularization in oxygen-induced retinopathy
      as the animal model of ROP without retinal cytotoxicity. These data suggests that
      CA could be a potent anti-angiogenic agent for retinal neovascularization, and be
      applied in the treatment of other vaso-proliferative retinopathies.

PMID- 19589398
TI  - Regulatory role of HIF-1alpha in the pathogenesis of age-related macular
      degeneration (AMD).
AB  - Age-related macular degeneration (AMD) is a leading cause of irreversible
      blindness in the elderly throughout the world. AMD is attributed to a complex
      interaction of genetic and environmental factors. It is characterized by
      degeneration involving the retinal photoreceptors, retinal pigment epithelium
      (RPE), and Bruch's membrane, as well as alterations in choroidal capillaries.
      Aging and age-associated degenerative diseases, such as AMD, are intimately
      associated with decreased levels of tissue oxygenation and hypoxia that may
      induce accumulation of detrimental RPE-associated deposits, inflammation and
      neovascularization processes in retina. Hypoxia-inducible factor (HIF) is the
      master regulator for hypoxia-induced cellular adaptation that is involved in NF
      kappaB signaling and the autophagic protein clearance system. In this review, we
      discuss role of HIF in AMD pathology and as a possible therapeutic target.

PMID- 19589399
TI  - A recombinant adenovirus prime-virus-like particle boost regimen elicits
      effective and specific immunities against norovirus in mice.
AB  - Prime-boost vaccination using recombinant viral vectors and proteins has emerged
      as a highly effective strategy for protecting against viral pathogens. However,
      the ability of such regimens to provide immunity against norovirus (NV), an
      important cause of acute epidemic gastroenteritis worldwide, has never been
      assessed. In this study, we analyzed NV-specific humoral, mucosal, and cellular
      immune responses following intranasal immunization with the recombinant
      adenovirus expressing the NV GGII4 capsid protein (rAd) prime-NV virus-like
      particle (VLP) boost, VLP prime-rAd boost, or repeated NV VLP regimens. Our
      results show that mice primed with rAd and boosted with VLP had stronger humoral,
      mucosal, and interferon-gamma responses than those immunized with VLP prime-rAd
      boost or VLP alone. These results demonstrate that adenovirus prime-VLP boost
      vaccination is an effective strategy for induction of immune responses against NV
      and is a promising strategy to improve current VLP-based NV vaccine development.

PMID- 19589396
TI  - New insights into the molecular mechanisms underlying effects of estrogen on
      cholesterol gallstone formation.
AB  - Epidemiological and clinical studies have found that at all ages women are twice
      as likely as men to form cholesterol gallstones, and this gender difference
      begins since puberty and continues through the childbearing years, which
      highlight the importance of female sex hormones. Estrogen is a crucial hormone in
      human physiology and regulates a multitude of biological processes. The actions
      of estrogen have traditionally been ascribed to two closely related classical
      nuclear hormone receptors, estrogen receptor 1 (ESR1) and ESR2. Recent studies
      have revealed that the increased risk for cholesterol gallstones in women vs. men
      is related to differences in how the liver metabolizes cholesterol in response to
      estrogen. A large number of human and animal studies have proposed that estrogen
      increases the risk of developing cholesterol gallstones by increasing the hepatic
      secretion of biliary cholesterol, which, in turn, leads to an increase in
      cholesterol saturation of bile. Furthermore, it has been identified that hepatic
      ESR1, but not ESR2, plays a major role in cholesterol gallstone formation in mice
      in response to high doses of 17beta-estradiol. The mechanisms mediating
      estrogen's action have become more complicated with the recent identification of
      a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), a member of the
      seven-transmembrane G protein-coupled receptor superfamily. In this review, we
      provide an overview of the evidence for the lithogenic actions of estrogen
      through ESR1 and discuss the cellular and physiological actions of GPR30 in
      estrogen-dependent processes and the relationship between GPR30 and classical
      ESR1 on gallstone formation.

PMID- 19589400
TI  - Psychometric properties of the French translation of the reduced KOOS and HOOS
      (KOOS-PS and HOOS-PS).
AB  - OBJECTIVE: To evaluate the psychometric properties of the French KOOS physical
      function (KOOS-PS) and HOOS physical function (HOOS-PS), specifically its
      feasibility, reliability, construct validity, and responsiveness. METHODS:
      Consecutive outpatients consulting for primary knee or hip osteoarthritis (OA) in
      a rheumatology department were included. During the initial assessment, patients
      were asked to complete the Knee injury and Osteoarthritis Outcome Score (KOOS) or
      Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaire and the
      OsteoArthritis Knee and Hip Quality Of Life questionnaire (OAKHQOL). The patients
      were given a second KOOS or HOOS questionnaire to complete and return by mail 2
      weeks later. Feasibility was assessed by calculating the percentage of missing
      items and the floor and ceiling effects. Test-retest reliability was evaluated
      using the intra-class correlation coefficient (ICC). Convergent and divergent
      construct validity was determined by comparing the results of the KOOS-PS or HOOS
      PS and OAKHQOL questionnaires using Spearman's rank test. Responsiveness was
      evaluated using data obtained in other hip or knee OA patients prior to and 1
      month after intra-articular hyaluronic acid injection, using standardized
      response mean (SRM) and effect-size (ES). RESULTS: Eighty-seven patients with
      knee OA and 50 hip OA patients were included. The KOOS-PS and HOOS-PS scores were
      obtained for all patients as there were no missing items. Neither a floor nor a
      ceiling effect was observed. The ICC of KOOS-PS and HOOS-PS was 0.861 (0.763
      0.921) and 0.859 (0.725-0.929), respectively. A strong or moderate correlation
      was observed, as expected, between KOOS-PS, HOOS-PS, and the OAKHQOL physical
      activities, pain, and mental health domains. A weak correlation was observed, as
      expected, between KOOS-PS, HOOS-PS, and the other OAKHQOL domains, except for a
      moderate correlation between the KOOS-PS and social functioning. The
      responsiveness was demonstrated with SRM and ES of 0.80 and 0.51 (KOOS-PS), 1.10
      and 0.62 (HOOS-PS), respectively. CONCLUSION: The French versions of KOOS-PS and
      HOOS-PS are reliable, valid, and responsive questionnaires for capturing
      functional disability in people with knee and hip OA.

PMID- 19589402
TI  - [Hemorrhage, hemostasis and thrombosis in surgery].

PMID- 19589403
TI  - [Hemorrhage, hemostasis and thrombosis in surgery].
AB  - Surgery is a leading cause of major hemorrhage as well as of thrombosis unless
      patients are administered appropriate antithrombotic prophylaxis after their
      thrombo-hemorrhagic risk has been stratified. Therefore, thorough preoperative
      evaluation is essential to minimize surgical complications. In cases of
      incoercible bleeding, drugs such as desmopressin, synthetic antifibrinolytics or
      recombinant factor VII can be administered. To prevent postoperative thrombosis,
      low molecular weight heparins or pentasaccharide have been shown to significantly
      reduce the incidence of thromboembolism.

PMID- 19589401
TI  - Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9
      gene.
AB  - Fibroblast growth factors (FGFs) play diverse roles in several developmental
      processes. Mutations leading to deregulated FGF signaling can cause human
      skeletal dysplasias and cancer.(1,2) Here we report a missense mutation
      (Ser99Asp) in exon 2 of FGF9 in 12 patients with multiple synostoses syndrome
      (SYNS) in a large Chinese family. In vitro studies demonstrate that FGF9(S99N) is
      expressed and secreted as efficiently as wild-type FGF9 in transfected cells.
      However, FGF9(S99N) induces compromised chondrocyte proliferation and
      differentiation, which is accompanied by enhanced osteogenic differentiation and
      matrix mineralization of bone marrow-derived mesenchymal stem cells (BMSCs).
      Biochemical analysis reveals that S99N mutation in FGF9 leads to significantly
      impaired FGF signaling, as evidenced by diminished activity of Erk1/2 pathway and
      decreased beta-catenin and c-Myc expression when compared with wild-type FGF9.
      Importantly, the binding of FGF9(S99N) to its receptor is severely impaired
      although the dimerization ability of mutant FGF9 itself or with wild-type FGF9 is
      not detectably affected, providing a basis for the defective FGFR signaling.
      Collectively, our data demonstrate a previously uncharacterized mutation in FGF9
      as one of the causes of SYNS, implicating an important role of FGF9 in normal
      joint development.

PMID- 19589404
TI  - [Antiplatelet agents and anticoagulants: management of the anticoagulated
      surgical patient].
AB  - Among the drugs most widely consumed by patients are both antiplatelet agents
      (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin,
      low molecular weight heparin, fondaparinux). The use of these drugs in the
      perioperative period is an essential concern in patient care due to the need to
      balance the risk of bleeding against thrombotic risk (arterial or venous), which
      is increased in surgical patients. The present review highlights three main
      aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week
      and 10 days before surgery to minimize perioperative bleeding. However, this
      practice has been questioned because patients without the required antiplatelet
      coverage may be at greater risk of developing cardiac, cerebral or peripheral
      vascular complications. Therefore, the recommendation of systematic antiplatelet
      withdrawal for a specific period should be rejected. Currently, risks should be
      evaluated on an individual basis to minimize the time during which the patient
      remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is
      required in most surgical patients due to the high prevalence of venous
      thromboembolic disease. This implies the use of anticoagulants and the practice
      of regional anesthesia has been questioned in these patients. However, with the
      safety recommendations established by the various scientific societies, this
      practice has been demonstrated to be safe. Finally, "bridge therapy" in patients
      anticoagulated with acenocoumarol should be performed on an individual basis
      rather than systematically without taking into account the thrombotic risks of
      each patient. The perioperative period involves high arterial and venous
      thrombotic risk and the optimal use of antiplatelet agents and anticoagulants
      should be a priority to minimize this risk without increasing hemorrhagic risk.
      Multidisciplinary consensus is essential on this matter.

PMID- 19589405
TI  - [Hemostasis and technology. Energy. Development of new technologies].
AB  - The hemostasis systems applied in surgery are based on endothermic heat
      production resulting from the interaction between energy and tissue. The most
      frequently used energy source is electrocoagulation, applied through two systems:
      monopolar and bipolar. More sophisticated electrocoagulation systems have
      progressively been developed such as the Argon beam, in which coagulation is
      superficial and does not injure the deep tissues, or LigaSure, based on the use
      of a bipolar system with an inbuilt feedback system allowing vessels to be sealed
      without excessive heat and a consequent reduction of collateral lesions. Another
      system that has been developed in the last few years is the ultrasonic scalpel,
      based on the ability of the cell membrane proteins to denature as a result of
      ultrasonic vibration. This system avoids some of the risks involved in the use of
      electrical energy such as accidental burns due to stray electrical current or
      faulty insulation of an instrument. Moreover, the harmonic scalpel reaches a
      temperature of no more than 100 degrees and the effect of lateral tissue
      destruction is much lower than with electrosurgery, although this reduction is
      negligible when compared with the electrosurgical methods developed in the last
      few years such as LigaSure. Another system that is also used is laser energy,
      consisting of a photon beam containing a specific wavelength; each photon moves
      in step with the others in both time and space. This system has not become widely
      used due to its high cost, the difficulty of controlling this type of energy, and
      the lack of objective advantages over conventional electrosurgery.

PMID- 19589406
TI  - [Topical hemostatic devices in surgery: between science and marketing].
AB  - Topical hemostatic agents have been used in surgery with varying degrees of
      success. These agents include oxidized cellulose, absorbable gelatin sponges,
      microfibrillar collagen and fibrin seals. Fibrin seals have become widely used as
      they improve perioperative hemostasis, reduce the need for red blood cell
      transfusions and prevent biliary leaks. Their widespread use, however, contrasts
      with the scarcity of data from controlled studies to support their clinical
      effectiveness. Therefore, a prospective, randomized, controlled, single-center
      study was performed in 300 patients who underwent elective hepatectomy, with and
      without application of fibrin seal on the raw liver surface. None of the
      variables evaluated (blood loss, transfusions, biliary fistulas and postoperative
      results) differed between the two groups. We conclude that the application of
      fibrin seal does not seem justified and that discontinuing its routine use would
      substantially reduce costs. The use of a new agent, Tachosil, is supported by a
      single multicenter, prospective, randomized, controlled trial, which is limited
      by the small number of patients and by the fact that the variable analyzed--time
      from application to hemostasis--may not be clinically relevant.

PMID- 19589407
TI  - [Management of hemorrhage in patients with abdominal trauma: application of the
      European Guidelines for the management of bleeding following major trauma].
AB  - In patients with traumatic intraabdominal hemorrhage, urgent decisions must be
      made. Resuscitation measures must often be simultaneously combined with
      diagnostic actions and measures to control the source of the bleeding.
      Hemorrhages are usually complicated by coagulation disorders and the presence of
      acidosis and hypothermia. In these conditions, emergency measures are required
      that usually involve various specialists. However, given the paucity of the
      scientific evidence in this field, the intervention protocols differ from one
      center to another. The European Guidelines for the management of bleeding
      following major trauma has recently been published. These guidelines review
      aspects such as evaluation and initial management of bleeding, localization and
      control of the source of bleeding and replacement of blood products. In addition,
      recommendations based on the best available evidence to 2008 are made. This
      review describes the basic aspects of traumatic intraabdominal hemorrhage.

PMID- 19589408
TI  - [Complex surgical techniques to control bleeding].
AB  - Massive bleeding is a major cause of intraoperative death or death in the
      immediate postoperative period as a result of surgery. The present article
      describes the basic principles for the control of surgical bleeding as well as
      temporary and definitive maneuvers. Temporary control of bleeding can often be
      achieved with simple maneuvers, which may not be definitive, in which case damage
      control or planned reoperation are required. The surgeon's aim should always be
      to control the bleeding. If simple maneuvers fail, more complex procedures are
      required. The present article also describes these maneuvers to control bleeding
      (Pringle's maneuver, total vascular exclusion, atrial caval shunt, Mattox's
      maneuver, Cattel Braasch maneuver, Kocher's maneuver and aortic control
      maneuvers).

PMID- 19589410
TI  - [Risk of venous thromboembolic disease in general surgery].
AB  - Despite preventive efforts, venous thromboembolic disease (VTED) is still a major
      problem for surgeons due to its frequency and the morbidity, mortality and
      enormous resource consumption caused by this entity. However, the most important
      feature of VTED is that it is one of the most easily preventable complications
      and causes of death. To take appropriate prophylactic decisions (indication,
      method, initiation, duration, etc.), familiarity with the epidemiology of VTED in
      general surgery and some of its most significant populations (oncologic,
      laparoscopic, bariatric, ambulatory and short-stay) is essential. These factors
      must also be known to determine the distinct risk factors in these settings with
      a view to stratifying preoperative risk.

PMID- 19589409
TI  - [Solid organ transection. Open and laparoscopic surgery].
AB  - Recent advances in liver surgery have reduced post-hepatectomy mortality to less
      than 5% in most units specialized in hepato-pancreatic-biliary surgery. Possibly,
      the single most important factor contributing to these improved results has been
      the reduction in intraoperative bleeding during liver parenchymal transection.
      Liver transection is the most risky part of the intervention due to the risk of
      massive hemorrhage. Some technological advances and refinements to the surgical
      technique have contributed to making this critical phase of liver surgery safer.
      Among these advances, the most notable are detailed knowledge of the surgical
      anatomy of the liver, vascular control techniques and methods of liver
      parenchymal transection. The present review describes current transection
      techniques, as well as their advantages and disadvantages. Until there is solid
      evidence on the best method, the choice of technique and instrument for liver
      transection depends mainly on the surgeon's personal preference. Nevertheless,
      some factors can influence the choice of method, such as the surgeon's
      experience, anesthetic management, type of hepatectomy (central, peripheral),
      type of approach (open, laparoscopic), quality of the liver (normal, cirrhotic,
      steatotic) and the availability of the instruments in the center.

PMID- 19589411
TI  - [Prevention of venous thromboembolic disease in general surgery].
AB  - Postoperative venous thromboembolic disease (VTED) affects approximately one in
      four general surgery patients who do not receive preventive measures. In addition
      to the risk of pulmonary embolism, which is often fatal, patients with VTED may
      develop long-term complications such as post-thrombotic syndrome or chronic
      pulmonary hypertension. In addition, postoperative VTED is usually asymptomatic
      or produces clinical manifestations that are attributed to other processes and
      consequently this complication is often unnoticed by the surgeon who performed
      the procedure. Thus, the most effective strategy consists of effective prevention
      of VTED using the most appropriate prophylactic measures against the patient's
      thromboembolic risk. There is sufficient evidence that VTED can be prevented by
      pharmacological methods, especially heparin and its derivatives and with
      mechanical methods such as support tights or intermittent pneumatic compression
      of the lower extremities. To reduce the incidence of VTED as far as possible,
      strategies have been proposed that include a combination of drugs and mechanical
      methods, new antithrombotic drugs, or prolonging the duration of prophylaxis in
      patients at very high risk, such as those who have undergone surgery for cancer.
      Another important aspect is the optimal moment to initiate prophylaxis with
      anticoagulant drugs with the aim of achieving an adequate equilibrium between
      antithrombotic efficacy and the risk of hemorrhagic complications. The present
      article reviews the available evidence to attempt to optimize prevention of VTED
      in general surgery and in some special groups, such as laparoscopic surgery,
      short-stay surgery and obesity.

PMID- 19589413
TI  - Computed tomography signs of pulmonary hypertension: old and new observations.
AB  - Pulmonary hypertension (PH) has a poor prognosis. It may be idiopathic or develop
      secondary to various cardiac and respiratory disorders. The diagnosis of PH is
      challenging because its signs and symptoms are non-specific and there is no
      completely reliable non-invasive test for its detection. Most patients with
      suspected PH or with the non-specific symptoms of PH will undergo computed
      tomography (CT) as part of their diagnostic work-up and, therefore, it is
      important for radiologists to be aware of the CT signs that may suggest the
      diagnosis. This article will review the numerous CT signs of PH describing their
      individual strengths and weaknesses, and discuss how they may be applied in
      clinical practice.

PMID- 19589414
TI  - Cardiovascular magnetic resonance imaging in the assessment of carcinoid heart
      disease.
AB  - Carcinoid disease arises from a low-grade neuroendocrine tumour derived from
      serotonin-producing enterochromaffin cells. It is the most common tumour
      affecting the small bowel. The majority of patients who progress to carcinoid
      syndrome develop cardiac disease selectively involving the right side of the
      heart, whereas left heart disease is unusual. The most common cause of death is
      dilatation and dysfunction of the right ventricle. Right ventricular dysfunction
      is largely secondary to pathological endocardial fibrosis of the tricuspid and
      pulmonary valves, presenting with regurgitation and stenosis. Average survival
      falls to only 11 months with the onset of symptoms, but recent evidence suggests
      that survival can be improved by early surgery in selected individuals. This
      article reviews the particular role that cardiovascular magnetic resonance
      imaging has in the management of carcinoid heart disease.

PMID- 19589415
TI  - Multidetector row CT of the brain and carotid artery: a correlative analysis.
AB  - AIM: To evaluate the association between types of carotid plaque, the presence of
      prior ischaemic events detectable with CT, and patient's symptoms. MATERIALS AND
      METHODS: Between January 2004 and May 2006, 112 patients were evaluated using
      multidetector row computed tomography angiography (MDCTA) of the carotid arteries
      and computed tomography (CT) of the brain. Carotid arteries were categorized by
      evaluating the degree of stenosis according to North American Symptomatic Carotid
      Endarterectomy Trial (NASCET) criteria, the type of plaque, and the presence of
      plaque ulceration. The brain was assessed via CT for the presence, type, and
      position of lesions. Chi-square tests, Student's t test, and simple logistic
      regression analysis were performed and the Cohen kappa test was applied for
      interobserver variability measurement. RESULTS: The Chi-square test indicated a
      statistically significant association between the presence of fatty plaques
      (p=0.005) and CT-detectable lesions in the brain (p=0.004). Moreover, the number
      of patients with CT-detectable brain lesions was greater in patients with >70%
      stenosis than in those with <70% stenosis (p=0.007). Logistic regression
      confirmed the association between fatty plaque and symptoms (p=0.001), between
      >70% stenosis and symptoms (p=0.041), and an inverse association between
      calcified plaque and symptoms (p=0.009). CONCLUSION: MDCTA allows adequate
      evaluation of the type of plaque. The results of the present study indicate that
      there is an association between cerebral lesions, symptoms, and fatty plaque in
      the carotid artery. The degree of stenosis also correlated with cerebral lesions
      and symptoms. According to the obtained data, the type of carotid plaque should
      be included among primary parameters in the classification of patients' risk
      class.

PMID- 19589416
TI  - Primary hepatic angiosarcoma: imaging findings and palliative treatment with
      transcatheter arterial chemoembolization or embolization.
AB  - AIM: To describe the image findings and results of transcatheter arterial
      chemoembolization (TACE) or transcatheter arterial embolization (TAE) for
      treating primary hepatic angiosarcoma. MATERIALS AND METHODS: A retrospective
      review of the electronic medical database from 2002 to 2007, revealed six
      patients with primary hepatic angiosarcoma confirmed by percutaneous liver
      biopsy. The computed tomography (CT) and angiography imaging findings, the TACE
      or TAE results, and the post-procedure course were evaluated in all patients.
      RESULTS: On CT and angiography, each tumour appeared as a solitary mass or as
      multiple nodules or masses with heterogeneously early and progressive
      enhancement. One of the two patients with tumour response to TACE died 8 months
      after initial presentation, and the remaining patient was still alive at the last
      follow-up 12 months after initial presentation. However, two patients with no
      response to TACE and two patients who underwent emergent TAE for tumour rupture
      died 1 week to 5 months (mean 2.1 months) after initial presentation.
      CONCLUSIONS: Primary hepatic angiosarcoma appears as a solitary or multiple,
      hypervascular lesions with heterogeneously early and progressive enhancement on
      CT and angiography. Although TAE may be the primary procedure for achieving
      emergent bleeding control caused by the rupture of hepatic angiosarcomas, TACE
      may be effective for treating patients with a dominant hepatic angiosarcoma with
      or without intrahepatic metastases.

PMID- 19589417
TI  - Retrodiaphragmatic portion of the lung: how deep is the posterior costophrenic
      sulcus on posteroanterior chest radiography?
AB  - AIM: To determine the depth of the posterior costophrenic sulcus (CPS) on
      posteroanterior (PA) chest radiography in relation to the diaphragmatic dome and
      lateral CPS. MATERIALS AND METHODS: Five hundred and forty consecutive PA chest
      radiographs that were performed for general health screenings were
      retrospectively reviewed. Among them 282 radiographs were selected that met the
      following criteria: visualization of the inferior boundary of the posterior CPS
      behind the right hemidiaphragm; and no abnormal findings that affected the shape
      and level of the diaphragm. The selected chest radiographs were from 155 men and
      127 women with a mean age of 40.7+/-8.4 years. On 282 PA chest radiographs, the
      distances between the right diaphragmatic dome and posterior CPS (total
      diaphragmatic height), the diaphragmatic dome and lateral CPS (diaphragmatic dome
      height), and the lateral and posterior CPS (posterior CPS depth) were measured.
      In addition levels of the right lateral and posterior CPS were scored in relation
      to levels of the thoracic and lumbar spines. The relationships between the
      posterior CPS depth and demographic and physical data and other radiographic
      measurements were analysed. RESULTS: The mean right posterior CPS depth was
      29.2+/-15.6 mm. The average level of the posterior CPS in relation to the spine
      was 13.5+/-0.6, i.e., the level of lower half of the L1 vertebral body. The
      posterior CPS depth had a tendency to be deeper in those participants who were
      taller (r=0.17, p<0.01), had a higher body mass index (BMI; r=0.25, p<0.01),
      longer total diaphragmatic height (r=0.55, p<0.01), and shorter diaphragmatic
      dome height (r=-0.18, p<0.01). CONCLUSION: As the posterior CPS is deeper than
      the lateral CPS by approximately 3 cm, and reaches, on average, to L1, the
      standard chest PA radiograph must include >3 cm below the level of lateral CPS,
      or should include the L1 spine.

PMID- 19589418
TI  - MRI findings of intracranial cystic meningiomas.
AB  - AIM: To report the magnetic resonance imaging (MRI) features of intracranial
      cystic meningiomas and compare these features in intra- and peritumoural cyst
      groups. MATERIALS AND METHODS: Fourteen cases of peritumoural cystic meningiomas
      were compared with 18 cases of intratumoural cystic meningiomas. All patients
      were examined using non-enhanced and contrast-enhanced MRI. Tumour location,
      tumour size, signal intensity, enhancement characteristics, and cystic changes
      were assessed. The MRI features were compared between the intra- and peritumoural
      cyst groups. RESULTS: Most cystic meningiomas comprised two or more cysts. The
      solid parts of the tumours showed moderate or marked enhancement after the
      injection of contrast material. An enhanced cyst wall was found in six out of 14
      cases in the peritumoural cyst group, but not in the intratumoural cyst group.
      Peritumoural cystic meningiomas were predominately located in the cerebral falx,
      whereas the intratumoural cystic meningiomas were predominantly found in frontal
      convexity (X(2)=7.434, p=0.024). The cysts were larger in the peritumoural cyst
      group than in the intratumoural cyst group (t=5.274, p=0.0258). Peritumoural
      oedema was more commonly found in the intratumoural cyst group (X(2)=6.863,
      p=0.008). Cystic meningiomas with solid parts located inside the cyst are
      reported for the first time. CONCLUSION: Cystic meningiomas, although uncommon,
      should be differentiated from other cystic intracranial lesions. Peri- and
      intratumoural cystic meningiomas have distinct MRI features. The present study
      provides the first report of two lesions with solid parts located inside the
      cyst, as well as one lesion with a calcified solid nodule and haemorrhage within
      the cyst.

PMID- 19589419
TI  - Ultrasound-guided vacuum-assisted excision of breast papillomas: review of 6
      years experience.
AB  - AIM: To review the outcome of vacuum-assisted removal of breast papillomas
      performed in the Bolton Breast Unit. MATERIALS AND METHODS: Twenty-six benign
      breast papillomas were excised using an ultrasound-guided, vacuum-assisted
      technique under local anaesthetic over a 6-year period. An 8G Mammotome was used
      for 12 lesions, an 11G Mammotome for 13 lesions and a 7G EnCor for one lesion.
      The mean lesion size was 9 mm (range 3-17 mm). The mean number of cores taken per
      case was nine. RESULTS: One patient developed a post-procedure haematoma, which
      did not require treatment. There were no other short-term complications. None of
      the papillomas were associated with atypia or malignancy. Subsequent breast
      imaging (mostly routine screening mammography) was reviewed and evidence of
      recurrence recorded. To date, 16 patients have received at least one subsequent
      routine screening mammogram, with a mean follow-up to latest mammogram of 30
      months. Mammographic evidence of papilloma regrowth has been observed in two
      patents, with a third patient presenting with recurrence of the original symptom
      of a palpable lump. All three recurrent lesions were surgically excised and
      confirmed to be benign papillomas. These lesions measured 6, 12, and 15 mm prior
      to the original vacuum-assisted excision. CONCLUSION: The findings suggests that
      vacuum-assisted removal is a satisfactory alternative to surgery for the majority
      of patients, but that particular attention should be paid to ensuring complete
      lesion removal in view of the relatively high recurrence rate in this series.

PMID- 19589420
TI  - An evaluation of radiographer performed and interpreted barium swallows and
      meals.
AB  - AIM: To determine whether radiographers are able to perform and interpret barium
      swallows and meals (BSM) to an acceptable standard. MATERIALS AND METHODS: A
      retrospective audit was performed of all radiographer-managed BSMs over a 4-year
      period in an acute hospital. Descriptive statistics were used to analyse patient
      demographics, radiation doses, referral sources, and imaging findings.
      Radiographer reports were compared with radiologist reports assumed to be the
      reference standard, and correlated with patient outcomes via electronic record
      searches and case note scrutiny. Reporting accuracy, sensitivity, and specificity
      were calculated. RESULTS: Three radiographers performed a total of 962 BSMs in
      the 4-year audit period, including a varied and complex case-mix. Only 13 (0.01%)
      cases were abandoned due to technical reasons, with all other examinations of
      diagnostic quality. Although radiation dose levels were initially variable,
      following the installation of modern fluoroscopy equipment they remained
      comfortably within the national and regional diagnostic reference levels.
      Consultant radiologists verified the majority of the radiographer reports, with
      the most experienced radiographer independently reporting 230 cases (24%). Follow
      up of patient outcome was possible in 935 cases. The overall radiographer
      accuracy based on the 935 cases was 98.9%, sensitivity 98%, and specificity
      98.9%. CONCLUSIONS: Appropriately trained radiographers are able to perform and
      interpret BSM examinations to a very high standard.

PMID- 19589421
TI  - Discriminative MRI features of fallopian tube masses.
AB  - Fallopian tube disease, both acute and chronic, is a common cause of a
      sonographically indeterminate adnexal mass and may mimic ovarian cancer. Magnetic
      resonance imaging (MRI) is now widely used as a problem-solving tool in these
      circumstances. The purpose of this review is to provide the discriminative MRI
      features of Fallopian tube masses and illustrate the key signs that establish
      their origin and nature. Familiarity with these characteristics enables
      distinction of tubal disease from malignant adnexal disease with major impact on
      management. On MRI, Fallopian tube disease exhibits features that parallel the
      classical sonographic findings, but which can be more reliably recognized due to
      improved contrast and spatial resolution, multiplanar capacity, effective field
      of view, and tissue characterization. Recognition of these characteristic
      morphological features and specific MRI signal patterns are key to a specific
      diagnosis. The anatomical and histopathological basis of these MRI signs is
      emphasized, covering also the differential diagnosis and pitfalls. Two new signs,
      "synechiae" and "amorphous shading", are also described that have not been well
      described previously in MRI of tubal disease.

PMID- 19589422
TI  - Imaging of the complications of peripherally inserted central venous catheters.
AB  - Peripherally inserted central catheters (PICC) are widely used to provide central
      venous access, often in chronically ill patients with long-term intravenous
      access requirements. There are a number of significant complications related to
      both insertion and maintenance of PICC lines, including catheter malposition,
      migration, venous thrombosis, and line fracture. The incidence of these
      complications is likely to rise as the number of patients undergoing intravenous
      outpatient therapy increases, with a corresponding rise in radiologist input.
      This paper provides an overview of the relevant peripheral and central venous
      anatomy, including anatomical variations, and outlines the complications of PICC
      lines. Imaging examples demonstrate the range of radiological findings seen in
      these complications.

PMID- 19589423
TI  - Intraductal oncocytic papillary neoplasm of the bile duct: ultrasonography and CT
      findings with pathological correlations.

PMID- 19589424
TI  - CT before lumbar puncture in meningitis--what every radiology trainee should
      know.

PMID- 19589425
TI  - MRI quantification of obesity.

PMID- 19589426
TI  - The UK nephrostomy audit. Can a voluntary registry produce robust performance
      data?

PMID- 19589428
TI  - Radiological features of Meckel's diverticulum and its complications.

PMID- 19589430
TI  - Addressing the obesity epidemic: time for the maternity services to act now but
      what strategies should we use?

PMID- 19589431
TI  - The 50-year history, controversy, and clinical implications of left ventricular
      outflow tract obstruction in hypertrophic cardiomyopathy from idiopathic
      hypertrophic subaortic stenosis to hypertrophic cardiomyopathy: from idiopathic
      hypertrophic subaortic stenosis to hypertrophic cardiomyopathy.
AB  - Dynamic obstruction to left ventricular (LV) outflow was recognized from the
      earliest (50 years ago) clinical descriptions of hypertrophic cardiomyopathy
      (HCM) and has proved to be a complex phenomenon unique in many respects, as well
      as arguably the most visible and well-known pathophysiologic component of this
      heterogeneous disease. Over the past 5 decades, the clinical significance
      attributable to dynamic LV outflow tract gradients in HCM has triggered a
      periodic and instructive debate. Nevertheless, only recently has evidence emerged
      from observational analyses in large patient cohorts that unequivocally supports
      subaortic pressure gradients (and obstruction) both as true impedance to LV
      outflow and independent determinants of disabling exertional symptoms and
      cardiovascular mortality. Furthermore, abolition of subaortic gradients by
      surgical myectomy (or percutaneous alcohol septal ablation) results in profound
      and consistent symptomatic benefit and restoration of quality of life, with
      myectomy providing a long-term survival similar to that observed in the general
      population. These findings resolve the long-festering controversy over the
      existence of obstruction in HCM and whether outflow gradients are clinically
      important elements of this complex disease. These data also underscore the
      important principle, particularly relevant to clinical practice, that heart
      failure due to LV outflow obstruction in HCM is mechanically reversible and
      amenable to invasive septal reduction therapy. Finally, the recent observation
      that the vast majority of patients with HCM have the propensity to develop
      outflow obstruction (either at rest or with exercise) underscores a return to the
      characterization of HCM in 1960 as a predominantly obstructive disease.

PMID- 19589432
TI  - Diagnostic, prognostic, and therapeutic implications of genetic testing for
      hypertrophic cardiomyopathy.
AB  - Over the last 2 decades, the pathogenic basis for the most common heritable
      cardiovascular disease, hypertrophic cardiomyopathy (HCM), has been investigated
      extensively. Affecting approximately 1 in 500 individuals, HCM is the most common
      cause of sudden death in young athletes. In recent years, genomic medicine has
      been moving from the bench to the bedside throughout all medical disciplines
      including cardiology. Now, genomic medicine has entered clinical practice as it
      pertains to the evaluation and management of patients with HCM. The continuous
      research and discoveries of new HCM susceptibility genes, the growing amount of
      data from genotype-phenotype correlation studies, and the introduction of
      commercially available genetic tests for HCM make it essential that the modern
      day cardiologist understand the diagnostic, prognostic, and therapeutic
      implications of HCM genetic testing.

PMID- 19589433
TI  - Reflections of inflections in hypertrophic cardiomyopathy.
AB  - The shape of Doppler velocity tracings in obstructive hypertrophic cardiomyopathy
      offers insights into its pathophysiology. Inflection points are the points on a
      curve where its shape changes from concave to convex, or vice versa. These
      dynamic systolic abnormalities are caused: 1) by the amplifying nature of the
      obstruction; and 2) by the adverse effect of the sudden imposition of afterload
      in midsystole. The midsystolic drop in left ventricular ejection velocities and
      the premature termination of longitudinal shortening are compelling evidence of
      the deleterious mechanical effect of obstruction on the ventricle. This dynamic
      systolic dysfunction, demonstrated on the Doppler curves, may contribute to heart
      failure symptoms and adverse outcome. In outflow obstruction, these abnormalities
      normalize after abolition of gradient. Therefore, their detection in an
      individual patient confirms obstruction as a therapeutic target.

PMID- 19589434
TI  - Hypertrophic cardiomyopathy phenotype revisited after 50 years with
      cardiovascular magnetic resonance.
AB  - OBJECTIVES: Our purpose was to characterize the pattern and distribution of left
      ventricular (LV) hypertrophy by cardiovascular magnetic resonance (CMR) to more
      precisely define phenotypic expression and its clinical implications in
      hypertrophic cardiomyopathy (HCM). BACKGROUND: Based on prior pathologic and 2
      dimensional echocardiographic studies, HCM has been regarded as a disease
      characterized by substantial LV wall thickening. METHODS: Cine and late
      gadolinium enhancement CMR were performed in 333 consecutive HCM patients (age 43
      +/- 17 years). RESULTS: Basal anterior LV free wall and the contiguous anterior
      ventricular septum were the most commonly hypertrophied segments (n = 256; 77%).
      LV hypertrophy was focal (involving < or = 2 segments [< or = 12% of LV]) in 41
      patients (12%), intermediate (3 to 7 segments [13% to 49% of LV]) in 112 patients
      (34%), and diffuse (> or = 8 segments [> or = 50% of LV]) in 180 patients (54%);
      42 patients (13%) showed hypertrophied segments separated by regions of normal
      thickness. The number of hypertrophied segments was greater in patients with LV
      outflow tract obstruction (> or = 30 mm Hg) than without (10 +/- 4 vs. 8 +/- 4
      per patient; p = 0.0001) and was associated with an advanced New York Heart
      Association functional class (p = 0.007). LV wall thickness was greater in
      segments with late gadolinium enhancement than without (20 +/- 6 mm vs. 16 +/- 6
      mm; p < 0.001). We also identified 40 (12%) of HCM patients with segmental LV
      hypertrophy largely confined to the anterolateral free wall, posterior septum, or
      apex, which was underestimated or undetected by echocardiography. CONCLUSIONS:
      Although diverse, patterns of LV hypertrophy are usually not extensive in HCM,
      involving < or = 50% of the chamber in about one-half the patients, and are
      particularly limited in extent in an important minority. Contiguous portions of
      anterior free wall and septum constituted the predominant region of wall
      thickening, with implications for clinical diagnosis. These observations support
      an emerging role for CMR in the contemporary evaluation of patients with HCM.

PMID- 19589435
TI  - Outcome of patients with hypertrophic cardiomyopathy and a normal
      electrocardiogram.
AB  - OBJECTIVES: This study sought to clarify the frequency, clinical phenotype, and
      prognosis of those patients with hypertrophic cardiomyopathy (HCM) who present
      with a normal electrocardiogram (ECG). BACKGROUND: Hypertrophic cardiomyopathy is
      the most common cause of sudden death in young people. Screening advocates have
      recommended a 12-lead ECG for the early detection of HCM in athletes, yet the
      clinical outcomes of those presenting with a normal ECG remains to be fully
      delineated. METHODS: Baseline characteristic and echocardiographic data were
      collected on all patients with HCM who initially presented to our institution
      with a diagnostic echocardiogram but a normal ECG. Follow-up was obtained and
      compared with the prognosis of HCM patients who presented with abnormal ECGs.
      RESULTS: We compared 135 HCM patients with a normal ECG with 2,350 HCM patients
      with an abnormal ECG. The latter group was more likely to have worse symptoms,
      have higher gradients, and a greater degree of septal wall thickness than the
      patients with a normal ECG. Severe obstructive symptoms requiring surgical
      myectomy and implantation of an implantable cardioverter-defibrillator were more
      common in patients with abnormal ECGs. Cardiac survival was significantly better
      in the group with a normal ECG at presentation-none of these patients had a
      cardiac death at follow-up. CONCLUSIONS: Almost 6% of patients presenting with
      demonstrable echocardiographic evidence of HCM had a normal ECG at the time of
      diagnosis. This subset of patients with normal ECG-HCM appears to exhibit a less
      severe phenotype with better cardiovascular outcomes.

PMID- 19589436
TI  - Outcome of mildly symptomatic or asymptomatic obstructive hypertrophic
      cardiomyopathy: a long-term follow-up study.
AB  - OBJECTIVES: The purpose of this study was to characterize the prognosis of
      minimally symptomatic patients with obstructive hypertrophic cardiomyopathy
      (HCM). BACKGROUND: Recent data have suggested that obstruction may be present in
      the majority of HCM patients, irrespective of cardiac symptoms. The prognosis of
      minimally symptomatic obstructive HCM remains poorly defined. METHODS: We
      examined 544 consecutive adult patients (age 59 +/- 16 years; 55% men) with
      obstructive HCM documented by Doppler echocardiography who were free of severe
      cardiac symptoms, and we performed clinical follow-up (median 9.3 years).
      RESULTS: There was only a slight excess mortality of the cohort in comparison to
      the expected survival of a similar U.S. general population (10-year observed vs.
      expected survival, 69.3% vs. 71.9%; p = 0.04) and 46% of the deaths were
      attributable to noncardiac causes. However, there was a clear relation between
      increasing severity of the left ventricular outflow tract (LVOT) gradient and
      outcome. For patients with high resting gradients (Doppler peak velocity >4 m/s),
      survival was significantly impaired (53% at 10 years; p = 0.001 vs. expected),
      and death or severe symptoms occurred in 68% of these patients within 10 years
      after the initial evaluation. Conversely, there was no impairment of long-term
      survival for patients with less-severe resting obstruction. Independent
      predictors of mortality in the entire cohort were age, prior stroke, and LVOT
      gradient severity. CONCLUSIONS: Patients with obstructive HCM and mild or no
      symptoms have only slight excess mortality. However, patients with markedly
      elevated resting LVOT gradients are at a high risk of heart failure and death.
      These findings may have important implications for therapy, including the timing
      of septal reduction therapy.

PMID- 19589437
TI  - Cardiac magnetic resonance detection of myocardial scarring in hypertrophic
      cardiomyopathy: correlation with histopathology and prevalence of ventricular
      tachycardia.
AB  - OBJECTIVES: In hypertrophic cardiomyopathy (HCM) patients undergoing surgical
      myectomy, we sought to determine the association between pre-operative cardiac
      magnetic resonance (CMR) findings, small intramural coronary arteriole dysplasia
      (SICAD) on histopathology, and ventricular tachycardia (VT). BACKGROUND:
      Myocardial scarring (fibrosis) and SICAD are frequently observed on
      histopathology in HCM patients. CMR measures wall thickness and detects scar.
      METHODS: Sixty symptomatic HCM patients (62% men; mean age 51 +/- 14 years), with
      preserved ejection fraction (mean 64 +/- 5%) and no angiographic coronary disease
      underwent CMR (cine and delayed post-contrast) using a Siemens 1.5 T scanner,
      followed by septal myectomy. Maximal basal septal thickness was recorded on cine
      CMR. Scar was determined (percentage of total myocardium) on delayed post
      contrast CMR images and quantified as none, mild (0% to 25%), moderate (26% to
      50%), or severe (>50%). VT was assessed using Holter monitoring. Degree of SICAD
      was determined (normal, mild, moderate, and severe) on histopathology of surgical
      specimen. RESULTS: SICAD and scar were seen in 45 (75%) and 38 (63%) patients,
      respectively. In 15 patients without SICAD, 12 (80%) had no scar; 23 (70%)
      patients with mild SICAD had mild scar on CMR. On multivariate analysis, degree
      of SICAD was independently associated with scar on CMR (Wald chi-square
      statistic: 6.8, p < 0.01). Patients with basal septal scar on CMR had higher VT
      frequency compared with those without (27% vs. 5%, p = 0.03). CONCLUSIONS: A
      strong association exists between degree of SICAD and myocardial scarring seen on
      CMR.

PMID- 19589438
TI  - Risk factors and mode of death in isolated hypertrophic cardiomyopathy in
      children.
AB  - OBJECTIVES: This study was designed to review outcomes of pediatric isolated
      hypertrophic cardiomyopathy (HCM) managed uniformly at a single institution and
      assess whether reported adult risk factors for sudden death are predictive in
      pediatric HCM. BACKGROUND: Cardiac death in HCM occurs suddenly (SCD) or may be
      nonsudden (non-SCD). Little data exists on non-SCD in children. Risk factors for
      SCD in adult HCM are characterized and consensus management strategies detailed.
      Their application to children is uncertain and treatment strategies vary.
      METHODS: A retrospective cohort study of children with HCM was performed. Primary
      end points were cardiac death and transplantation. Frequency and outcomes of
      known adult risk factors were assessed. Outcomes analysis was performed using
      Kaplan-Meier curves and Cox regression analysis. RESULTS: Ninety-six patients
      were included. The average age at diagnosis was 10.6 +/- 5.4 years, and mean
      follow-up was 6.4 +/- 5.2 years. Primary end points occurred in 11 patients over
      the 20-year follow-up (11%), 4 underwent cardiac transplant and 7 died (3
      suddenly). Extreme left ventricular hypertrophy (z-score: >6) and an abnormal
      blood pressure response to exercise were predictive of non-SCD (p < 0.02 and p <
      0.03, respectively). Kaplan-Meier survival analysis predicts an 82% survival over
      a 20-year period. CONCLUSIONS: In children with isolated HCM managed primarily
      with exercise restriction and medication, cardiac death occurred infrequently.
      Non-SCD or transplant was at least as common as SCD. Extreme left ventricular
      hypertrophy and blunted blood pressure response to exercise were associated with
      an increased risk of non-SCD.

PMID- 19589439
TI  - Aortic stiffness is increased in hypertrophic cardiomyopathy with myocardial
      fibrosis: novel insights in vascular function from magnetic resonance imaging.
AB  - OBJECTIVES: The aim of the study was to determine if patients with hypertrophic
      cardiomyopathy (HCM), both with and without myocardial fibrosis, have altered
      aortic stiffness as assessed by magnetic resonance imaging (MRI) pulse wave
      velocity (PWV) measurements. BACKGROUND: Abnormal aortic stiffness implies an
      unfavorable prognosis and has been established in a variety of aortic diseases
      and ischemic cardiomyopathy. However, the relationship between aortic stiffness
      and HCM has not been studied previously. METHODS: The study was institutional
      review board approved and Health Insurance Portability and Accountability Act of
      1996 compliant. Velocity-encoded MRI was performed in 100 HCM and 35 normal
      control subjects. PWV was determined between the mid-ascending and -descending
      thoracic aorta. Delayed-enhancement MRI was acquired for identification of
      myocardial fibrosis. RESULTS: Mean age was 52.4 years in HCM and 45.3 years in
      control subjects. The prevalence of myocardial fibrosis in HCM was 70%. PWV was
      significantly higher in HCM patients compared with control subjects (8.72 +/-
      5.83 m/s vs. 3.74 +/- 0.86 m/s, p < 0.0001). PWV was higher (i.e., increased
      aortic stiffness) in HCM patients with myocardial fibrosis than in those without
      (9.66 +/- 6.43 m/s vs. 6.51 +/- 3.25 m/s, p = 0.005). CONCLUSIONS: Increased
      aortic stiffness, as indicated by increased PWV, is evident in HCM patients, and
      is more pronounced in those with myocardial fibrosis. Further, aortic stiffening
      may adversely affect left ventricular performance. In addition, increased aortic
      stiffness correlates with myocardial fibrosis, and may represent another
      potentially important parameter for risk stratification in HCM, warranting
      further study.

PMID- 19589440
TI  - Hypertrophic cardiomyopathy, fibrosis, and aortic stiffness: an unidentified
      association unraveled by magnetic resonance imaging.

PMID- 19589441
TI  - The Extramural Division of Cardiovascular Sciences of the National Heart, Lung,
      and Blood Institute.

PMID- 19589442
TI  - The everolimus-eluting stent in real-world patients: 6-month follow-up of the X
      SEARCH (Xience V Stent Evaluated at Rotterdam Cardiac Hospital) registry.
AB  - OBJECTIVES: The purpose of this study was to investigate the impact of everolimus
      eluting stents (EES) in comparison with bare-metal stents (BMS), sirolimus
      eluting stents (SES), and paclitaxel-eluting stents (PES) on the 6-month clinical
      outcomes in an all-comer population. BACKGROUND: EES have been shown to be
      effective in the context of randomized trials with selected patients. The effect
      of EES implantation in more complex, unselected patients cannot be directly
      extrapolated from these findings. METHODS: In total, 649 consecutive unselected
      patients treated exclusively with EES were enrolled. Six-month clinical end
      points were compared with 3 historical cohorts (BMS, n = 450; SES, n = 508; and
      PES, n = 576). Major adverse cardiac events (MACE) were defined as a composite of
      all-cause mortality, myocardial infarction, or target vessel revascularization
      (TVR). RESULTS: The patients treated with EES were older, presented more
      frequently with acute myocardial infarction, and had more complicated lesions
      than the other groups. The EES group demonstrated a higher incidence of all-cause
      mortality than the SES group and a lower incidence of TVR than the BMS group.
      Multivariate adjustment demonstrated that BMS was associated with higher TVR and
      MACE risk than EES (adjusted hazard ratio [HR] for TVR: 2.02 [95% confidence
      interval (CI): 1.11 to 3.67]; adjusted HR for MACE: 2.15 [95% CI: 1.36 to 3.42]);
      that SES had a clinical outcome similar to that of EES, and that PES had a higher
      risk of MACE than did EES (adjusted HR: 1.57 [95% CI: 1.02 to 2.44]).
      CONCLUSIONS: This study suggests that the use of EES in an unselected population
      may be as safe as and more effective than BMS, may be as safe and effective as
      SES, may be as safe as PES, and may be more effective than PES.

PMID- 19589443
TI  - Successful treatment of an unusual cause of myocardial ischemia.

PMID- 19589444
TI  - Dual renin-angiotensin system blockade in heart failure.

PMID- 19589445
TI  - Dual renin-angiotensin system blockade and kidney disease.

PMID- 19589448
TI  - Influenza vaccination among adults with asthma findings from the 2007 BRFSS
      survey.
AB  - BACKGROUND: Asthma prevalence among U.S. adults is estimated to be 6.7%. People
      with asthma are at increased risk of complications from influenza. Influenza
      vaccination of adults and children with asthma is recommended by the Advisory
      Committee on Immunization Practices. The Healthy People 2010 Objectives call for
      annual influenza vaccination of at least 60% of adults aged 18-64 years with
      asthma and other conditions associated with an increased risk of complications
      from influenza. PURPOSE: To assess influenza vaccination coverage among adults
      with asthma in the United States. METHODS: Data from the 2007 Behavioral Risk
      Factor Surveillance System restricted to individuals interviewed during February
      through August were analyzed in 2008 to estimate national and state prevalence of
      self-reported receipt of influenza vaccination among respondents aged 18-64 years
      with asthma. Logistic regression provided predictive marginal vaccination
      coverage for each covariate, adjusted for demographic and access to care
      characteristics. RESULTS: Among adults aged 18-64 years with asthma, influenza
      vaccination coverage was 39.9% (95% CI=38.3%, 41.5%) during the 2006-2007 season
      (coverage ranged from 26.9% [95% CI=19.8%, 35.3%] in California to 53.3% [95%
      CI=42.8%, 63.6%] in Tennessee). Influenza vaccination coverage was 33.9% (95%
      CI=31.9%, 35.9%) for adults aged 18-49 years with asthma compared to 54.7% (95%
      CI=52.4%, 57.0%) for adults aged 50-64 years with asthma. Among people aged 18-64
      years, vaccination coverage was 28.8% among those without asthma. People with
      asthma who had an increased likelihood of vaccination were aged 50-64 years,
      female, non-Hispanic white, and had diabetes, activity limitations, health
      insurance, a regular healthcare provider, routine checkup in the previous year,
      and formerly smoked or never smoked. CONCLUSIONS: Influenza vaccination coverage
      continues to be below the national objective of 60% for people aged 18-64 years
      with asthma as a high-risk condition. Increased state and national efforts are
      needed to improve influenza vaccination levels among this population and
      particularly among those aged 18-49 years.

PMID- 19589447
TI  - Effect of a multimodal reminder program on repeat mammogram screening.
AB  - BACKGROUND: Patient mammogram reminders are effective but have not been fully
      implemented in practice to improve routine screening. The effectiveness of
      implementation and maintenance phases of a multimodal reminder program that
      incorporated automated calls capable of efficiently reaching large numbers of
      women was evaluated to improve repeat mammography screening. DESIGN: A quasi
      experimental study was conducted in 2008 using electronic medical record data
      during three time periods: pre-reminder phase (2004), post-reminder
      implementation phase (2006), and post-reminder maintenance phase (January 1-July
      1, 2007). SETTING/PARTICIPANTS: Participants were female Kaiser Permanente
      Northwest HMO members aged 42 years or more who were 20 months past their last
      mammogram (index date) (N=35,104). The intervention program targeted women aged
      50-69 years. Women aged 42-49 years (for whom clinical guidelines also recommend
      mammography) not targeted by the program constituted the primary comparison group
      (CG1). INTERVENTION: A "mammogram due soon" postcard was mailed to participants
      20 months after their last mammogram, followed by up to two automated phone calls
      and one live call for nonresponders. MAIN OUTCOME MEASURES: The outcome measure
      was the time until participants received a mammogram in the 10 months following
      the index date. RESULTS: Pre-reminder, 63.4% of targeted women completed a
      mammogram; this number increased to 75.4% in the post-reminder implementation
      phase; 80.6% completed a mammogram in the maintenance phases. After controlling
      for demographics and clinic visits, intervention women were 1.51 times more
      likely to complete a mammogram (CI=1.40, 1.62) post-reminder implementation,
      compared to CG1. The effect was maintained in 2007 (hazard ratio 1.81, CI=1.65,
      1.99). CONCLUSIONS: The study found that this multimodal reminder system could be
      effectively implemented and maintained in a large health system. If widely
      implemented, this intervention could substantially improve community mammography
      screening.

PMID- 19589449
TI  - Social smoking implications for public health, clinical practice, and
      intervention research.
AB  - BACKGROUND: Social smoking is increasingly prevalent and poses a challenge to
      traditional cessation practices. Tobacco companies conducted extensive research
      on social smokers long before health authorities did and marketed products to
      promote this smoking behavior. PURPOSE: Research is described and mechanisms
      identified that are used to promote social smoking to help improve cessation
      strategies in this growing group. EVIDENCE ACQUISITION: Searches from 2006 to
      2008 of previously secret tobacco industry documents using keywords social
      smoker, light smoker, casual smoker, youth smoker, and occasional smoker,
      followed by snowball searching. Data analysis was conducted in 2008. EVIDENCE
      SYNTHESIS: Tobacco industry research identified characteristics of social smokers
      that include: (1) denial of personal nicotine addiction; (2) self-categorization
      as a nonsmoker; (3) propensity for decreased tobacco use in response to smoke
      free laws; (4) variations in age, education, ethnicity, and socioeconomic
      backgrounds; and (5) a perceived immunity to personal health effects of tobacco
      but fear of consequences to others. Tobacco companies developed marketing
      strategies aimed at social smokers, including "non-habit forming" cigarettes.
      CONCLUSIONS: Previously considered a transient behavior, social smoking is also a
      stable consumption pattern. Focused clinical questions to detect social smoking
      are needed and may include, "Have you smoked any cigarettes or used any tobacco
      products in the past month?" as opposed to "Are you a smoker?" Clinicians should
      recognize that social smokers might be motivated to quit after education on the
      dangers of secondhand smoke rather than on personal health risks or with
      pharmacotherapy.

PMID- 19589450
TI  - Engaging parents to increase youth physical activity a systematic review.
AB  - BACKGROUND: Parents are often involved in interventions to engage youth in
      physical activity, but it is not clear which methods for involving parents are
      effective. PURPOSE: A systematic review was conducted of interventions with
      physical activity and parental components among healthy youth to identify how
      best to involve parents in physical activity interventions for children. EVIDENCE
      ACQUISITION: Identified intervention studies were reviewed in 2008 for study
      design, description of family components, and physical activity outcomes. The
      quality of reporting was assessed using the CONSORT checklist for reporting on
      trials of nonpharmacologic treatments. EVIDENCE SYNTHESIS: The literature search
      identified 1227 articles, 35 of which met review criteria. Five of the 14 RCTs
      met > or =70% of CONSORT checklist items. Five general procedures for involving
      parents were identified: (1) face-to-face educational programs or parent
      training, (2) family participatory exercise programs, (3) telephone
      communication, (4) organized activities, and (5) educational materials sent home.
      Lack of uniformity in reporting trials, multiple pilot studies, and varied
      measurements of physical activity outcomes prohibited systematic conclusions.
      Interventions with educational or training programs during family visits or via
      telephone communication with parents appear to offer some promise. CONCLUSIONS:
      There is little evidence for effectiveness of family involvement methods in
      programs for promoting physical activity in children, because of the
      heterogeneity of study design, study quality, and outcome measures used. There is
      a need to build an evidence base of more-predictive models of child physical
      activity that include parent and child mediating variables and procedures that
      can effect changes in these variables for future family-based physical activity
      interventions.

PMID- 19589451
TI  - Identifying clusters of active transportation using spatial scan statistics.
AB  - BACKGROUND: There is an intense interest in the possibility that neighborhood
      characteristics influence active transportation such as walking or biking. The
      purpose of this paper is to illustrate how a spatial cluster identification
      method can evaluate the geographic variation of active transportation and
      identify neighborhoods with unusually high/low levels of active transportation.
      METHODS: Self-reported walking/biking prevalence, demographic characteristics,
      street connectivity variables, and neighborhood socioeconomic data were collected
      from respondents to the 2001 California Health Interview Survey (CHIS; N=10,688)
      in Los Angeles County (LAC) and San Diego County (SDC). Spatial scan statistics
      were used to identify clusters of high or low prevalence (with and without age
      adjustment) and the quantity of time spent walking and biking. The data, a subset
      from the 2001 CHIS, were analyzed in 2007-2008. RESULTS: Geographic clusters of
      significantly high or low prevalence of walking and biking were detected in LAC
      and SDC. Structural variables such as street connectivity and shorter block
      lengths are consistently associated with higher levels of active transportation,
      but associations between active transportation and socioeconomic variables at the
      individual and neighborhood levels are mixed. Only one cluster with less time
      spent walking and biking among walkers/bikers was detected in LAC, and this was
      of borderline significance. Age-adjustment affects the clustering pattern of
      walking/biking prevalence in LAC, but not in SDC. CONCLUSIONS: The use of spatial
      scan statistics to identify significant clustering of health behaviors such as
      active transportation adds to the more traditional regression analysis that
      examines associations between behavior and environmental factors by identifying
      specific geographic areas with unusual levels of the behavior independent of
      predefined administrative units.

PMID- 19589452
TI  - Real noise from the urban environment: how ambient community noise affects health
      and what can be done about it.
AB  - The increasing interest in the potential effects of the community environment on
      individual health has so far excluded those of the acoustic environment. Yet it
      has long been recognized that continued exposure to elevated sound levels leads
      to noise-induced hearing loss. Noise is defined as unwanted sound that disturbs
      communication and speech intelligibility and interferes with sleep and mental
      tasks. Evidence points to numerous psychophysiologic outcomes of sustained
      exposure, including annoyance, reduced performance, aggressive behavior, and
      increased risk of myocardial infarction. Populated areas have experienced a
      steady rise in outdoor ambient noise resulting from increases in vehicular
      traffic and the ubiquitous use of machinery. In 2000, the WHO produced guidelines
      on occupational and community noise. The European Union mandated noise
      surveillance and abatement programs in cities. In the U.S., a few cities have
      revised their noise ordinances, but proactive noise reduction initiatives remain
      confined to new transportation infrastructure projects, thus leaving a large
      portion of the population at risk. Adding community noise to the public health
      agenda seems timely. Research needs to measure population-wide health effects of
      involuntary long-term exposure to ambient noise. Further study of the range and
      severity of co-morbidities will help refine the thresholds used to protect
      health. Policies and interventions, including health impact assessments, will
      require detailed data on actual ambient noise levels. Reducing noise at the
      source will likely require new road standards and lower allowable engine noise
      levels. Finally, noise abatement programs have an environmental justice dimension
      and need to target the at-risk population.

PMID- 19589453
TI  - PEDIATRIC NEUROLOGY: then and now.

PMID- 19589454
TI  - Common causes of uncommon seizures.
AB  - Afebrile seizures associated with rotavirus gastroenteritis, respiratory
      syncytial virus bronchiolitis, influenza infection, asthma, blood transfusions,
      and intake of a number of drugs (including theophylline, cephalosporins,
      metronidazole, and acyclovir) with therapeutic drug levels are uncommonly
      encountered in clinical practice. Reviewed here are the incidence, etiology,
      clinical presentation, types, diagnosis, associated electroencephalographic
      changes, and cranial magnetic resonance imaging findings in the literature, as
      well as management and prognosis of these seizures.

PMID- 19589455
TI  - Dexmedetomidine for procedural sedation in children with autism and other
      behavior disorders.
AB  - Dexmedetomidine has been increasingly in use for pediatric noninvasive procedural
      sedation. This retrospective study examined experience in children with autism
      and other neurobehavioral disorders, populations often difficult to sedate.
      Records of children with autism or neurobehavioral disorders sedated with
      dexmedetomidine at Chris Evert Children's Hospital and Kosair Children's Hospital
      were reviewed. Demographic and sedation-related data were collected, including
      sedative doses, time to sedation, efficacy, and complications. Comparisons of
      sedative doses, efficacy between autism and neurobehavioral patients, and
      analysis of age-related factors were performed. In all, 315 patients were
      sedated, most commonly for magnetic resonance imaging. Mean induction and total
      dexmedetomidine doses were 1.4 +/- 0.6 and 2.6 +/- 1.6 microg/kg, respectively,
      with no differences between autism and neurobehavior patients. Most patients
      (90%) patients received concomitant midazolam. There was an age-related decrease
      in dexmedetomidine dose, independent of midazolam use. Seven patients required
      intervention for hypotension, bradycardia, or both, and only one adverse
      respiratory event (obstruction requiring nasopharyngeal airway placement)
      occurred. There were two episodes of overt recovery-related agitation. All but
      four procedures were successfully completed (4/315, or 98.7%). Dexmedetomidine
      with or without midazolam was an effective sedative in this population. The
      regimen appeared to be well tolerated with few adverse events, including recovery
      related agitation, and appears to be an attractive option for this population.

PMID- 19589456
TI  - Development of visuospatial ability and kanji copying in Williams Syndrome.
AB  - Williams syndrome is known for uneven cognitive abilities. Visuospatial
      difficulties such as a failure in constructing objects are considered to be
      characteristic and may influence the copying of Japanese semantic characters,
      kanji. In contrast to previous investigations, which were done mainly cross
      sectionally, this study focused on the developmental aspects of the symptoms, to
      get a better view of the mechanism. Developmental changes in visuospatial
      abilities (including copying two-dimensional figures, three-dimensional figures,
      and kanji) in four boys with Williams syndrome, ages 4 to 11 years, were
      longitudinally observed for 6-9 years. The Benton's three-dimensional block
      construction tests and the Yerkes test were also performed. Some of the results
      were compared with those of mental age-matched children. The observation revealed
      improvements in performance for copying two-dimensional figures, as well as for
      copying kanji, in the Williams syndrome participants; however, copying three
      dimensional figures tended to remain difficult, especially if in a transparent
      view. Obtaining three-dimensional information using pictorial cues seemed to
      remain difficult for the Williams syndrome participants even at the later stage
      of study monitoring. This difficulty might be correlated with the core
      dysfunction of Williams syndrome.

PMID- 19589457
TI  - Divalproex sodium in children with partial seizures: 12-month safety study.
AB  - This phase III, open-label, multicenter, outpatient study evaluated the 12-month
      safety of valproate using divalproex sodium sprinkle capsules for partial
      seizures, with or without secondary generalization, in children aged 3-10 years
      (n = 169). Laboratory parameters and vital signs were assessed, and the Wechsler
      Scales of Intelligence, the Developmental Profile-II, movement-related items from
      the Udvalg for Kliniske Undersogelser, and the Behavior Assessment System for
      Children were administered. Efficacy was measured by the 4-week seizure rate. The
      most common treatment-emergent adverse events in the 169 study patients were
      typical childhood illnesses: pyrexia (18%), cough (17%), and nasopharyngitis
      (14%). The most common adverse events not considered typical childhood illnesses
      were vomiting (14%), tremor (9%), somnolence (8%), and diarrhea (8%). Of the 169
      patients, 11 (6.5%) were hospitalized with serious treatment-emergent adverse
      events. Although elevated ammonia levels were observed in 31 treated patients,
      and mean increases in uric acid concentrations and decreases in platelets were
      observed, the majority of patients were asymptomatic. Except for tremor, no
      increases in movement-related adverse effects were observed. Small numeric
      improvements were reported in the Wechsler Scales and the Behavior Assessment
      System for Children. The safety findings in this 12-month study are generally
      consistent with previous reports of valproate in adult and pediatric epilepsy
      patients.

PMID- 19589458
TI  - Factors influencing the evolution of West syndrome to Lennox-Gastaut syndrome.
AB  - This study examines factors influencing the evolution of West syndrome to Lennox
      Gastaut syndrome. The study population comprised 98 patients diagnosed with West
      syndrome and monitored for at least 3 years. During follow-up, West syndrome
      evolved to Lennox-Gastaut syndrome in 48 of the 98 patients. Etiology analysis
      indicated that West syndrome was cryptogenic in 36 patients (36.7%) and
      symptomatic in 62 (63.3%). West syndrome was managed with antiepileptic drugs in
      31 patients, ketogenic diets in 33 patients, hormonal therapy with prednisolone
      in 45 patients and with adrenocorticotropic hormone in 15 patients, epileptic
      surgery in 3 patients, and either no treatment or only herbal medication in 4
      patients. The risk of developing Lennox-Gastaut syndrome was significantly lower
      in patients who were placed on a ketogenic diet, given prednisolone or
      adrenocorticotropic hormone, or treated with a combination of these two therapies
      (bivariate logistic regression analysis, P < 0.05). There was no relationship
      between the development of Lennox-Gastaut syndrome and age at West syndrome onset
      or disease etiology. In conclusion, a ketogenic diet and hormonal therapy may
      play key roles in preventing encephalopathy in patients with West syndrome.

PMID- 19589459
TI  - Febrile seizures: characterization of double-stranded RNA-induced gene
      expression.
AB  - An association has long been suspected between febrile seizures and interleukin
      1beta, the most potent endogenous pyrogen. Interleukin-1beta production increases
      after double-stranded RNA stimulation in leukocytes of febrile seizure patients.
      To elucidate the genetics of the immune response, the gene expression pattern
      after double-stranded RNA stimulation was investigated using DNA microarray.
      Compared with the control group, expression of the genes ACCN4 (sodium channel),
      KCNC3 (potassium channel), GABRE (gamma-aminobutyric acid receptor epsilon
      subunit), RIPK2 (receptor interacting protein kinase-2), TLR4 (toll-like receptor
      4), IL26 (interleukin-26), and TNF (tumor necrosis factor), and CASP1 (caspase-1)
      was increased in the febrile seizure group (P < 0.01). Because RIPK2 and CASP1
      are associated with interleukin-1beta production, increased expression might
      cause increased interleukin-1beta production in the febrile seizure patients. The
      induced expression of several ion channel genes by double-stranded RNA may affect
      neuronal excitability which leads to seizure susceptibility during infection.

PMID- 19589460
TI  - Adherence of adolescents to multiple sclerosis disease-modifying therapy.
AB  - In this mixed-methods study, utilization data for disease-modifying therapies
      were reviewed to determine the adherence rate among our pediatric multiple
      sclerosis cohort. Adolescents were interviewed to explore their experiences with
      multiple sclerosis and the impact of peer relationships on adherence to
      treatment. Seventeen adolescents (6 male, 11 female) started interferon beta or
      glatiramer acetate before age 18. The mean age at first drug start date was 15.8
      years. Eight of the adolescents (47%) discontinued treatment after a median
      duration of 20 months. Many of the adolescents struggled to integrate the
      injections into their daily lives, with peers either facilitating or impeding
      this transition. In conclusion, adolescents in this cohort had difficulty
      adhering to disease-modifying therapies, and peers played an important role in
      mediating their adjustment to multiple sclerosis. Specific strategies are
      required to improve adolescents' adherence to treatment, including less intrusive
      options and enhancing peer support.

PMID- 19589461
TI  - Stroke in sickle cell anemia: alternative etiologies.
AB  - Stroke is common in children with sickle cell anemia, but is rarely attributed to
      the traditional causes of stroke identified in other children. An 11-year-old
      girl with sickle cell anemia presented with severe headache and was found to have
      recurrent bilateral multifocal strokes in a cardioembolic pattern. Evaluation
      revealed the presence of a patent foramen ovale, antiphospholipid antibodies, and
      elevations in factor VIII and lipoprotein(a). Sickle cell anemia is itself a
      hypercoagulable state with potential for increased right heart pressures, both of
      which predispose to paradoxical embolization via right-to-left intracardiac
      shunting of emboli, thus causing stroke. The present case suggests that the more
      traditional etiologies for pediatric stroke may also cause stroke in children
      with sickle cell anemia.

PMID- 19589462
TI  - Emery-Dreifuss muscular dystrophy: a novel mutation in the LMNA gene.
AB  - Described here is the phenotypical expression of a novel LMNA mutation c.1157 G>T
      in a Czech patient with an early-onset form of Emery-Dreifuss muscular dystrophy.
      The mutation predicts aberrant splicing. Now 21 years old, the patient has had
      slowly progressing muscle dystrophy since the age of one and early contractures
      of elbows. He is the only family member affected. Even though the dystrophy
      typically affects the heart as well, in the present case these signs are not yet
      expressed.

PMID- 19589464
TI  - A family with paroxysmal nonkinesigenic dyskinesia: genetic and treatment issues.
AB  - Paroxysmal nonkinesigenic dyskinesia is a condition characterized by attacks of
      sudden involuntary movements triggered by caffeine or alcohol intake, stress, or
      fatigue. The paroxysms are usually of the generalized type and may last up to an
      hour. Described here is a Polish family with this disorder seen in two children
      and their father. Variable expressivity as well as reduced penetrance of the
      causative mutation were noteworthy in this kindred. Treatment options included
      abortive diazepam and prophylactic levetiracetam, with the latter having a more
      pronounced effect in this family. Favorable response to levetiracetam is probably
      linked to action of the drug on calcium channels in neurons, muscle cells, or
      both.

PMID- 19589463
TI  - Mitochondrial encephalomyopathy lactic acidosis and strokelike episodes mimicking
      occipital idiopathic epilepsy.
AB  - We report on a 19-year-old man with a 9-year history of occipital seizures
      characterized by deviation of the eyes and tonic ipsilateral turning of the head
      during sleep, initially diagnosed as idiopathic childhood occipital epilepsy,
      Gastaut type. The eventual development of status epilepticus, associated with a
      T(1) hypointense as well as T(2), fluid-attenuated inversion recovery, and
      diffusion-weighted hyperintense brain lesion led to pathologic and genetic
      testing that identified a A3243G mitochondrial DNA point mutation associated with
      mitochondrial, encephalomyopathy, lactic acidosis, and strokelike episodes. This
      case emphasizes that occipital epileptic seizures can be the only presenting and
      long-lasting sign in patients with mitochondrial, encephalomyopathy, lactic
      acidosis, and strokelike episodes.

PMID- 19589465
TI  - Cranial MRI in acute hyperammonemic encephalopathy.
AB  - Cranial magnetic resonance imaging was performed in three cases of acute
      hyperammonemic encephalopathy with three diverse etiologies: infantile
      citrullinemia, acute hepatic encephalopathy, and proximal urea cycle disorder.
      All three patients exhibited diffuse extensive cortical signal changes and
      swelling. Neurologic outcome was poor in all three cases. Knowledge of the
      magnetic resonance imaging findings of hyperammonemic encephalopathy may help in
      early diagnosis and treatment and could influence the neurologic outcome.

PMID- 19589466
TI  - Is a reversible splenial lesion a sign of encephalopathy?
AB  - A reversible splenial lesion of the corpus callosum has been recognized in
      patients with mild encephalitis/encephalopathy associated with various infectious
      diseases. All reported cases of encephalitis/encephalopathy, by definition,
      present with neurologic signs, many of which involve seizures or mildly altered
      states of consciousness, such as drowsiness. We report an 8-year-old boy with
      influenza A infection not associated with neurologic signs, whose brain magnetic
      resonance images incidentally revealed a reversible splenial lesion in the corpus
      callosum. This case indicates that a transient splenial lesion in the corpus
      callosum may occur during a febrile illness, without neurologic manifestations.
      Therefore, physicians should not diagnose or treat a patient as encephalopathic
      merely because of the presence of a splenial lesion on magnetic resonance
      imaging.

PMID- 19589467
TI  - Early cortical cytotoxic edema in meningococcal meningitis.
AB  - Meningococcal disease frequently presents neurologic sequels via vascular,
      metabolic, or inflammatory processes. Understanding the underlying pathogenic
      mechanisms may influence both treatment and outcome. We present a 2-year-old
      child affected by Neisseria meningitidis sepsis, who on the second day from
      clinical onset manifested recurrent partial motor seizures and focal neurologic
      signs. An early magnetic resonance angiography of the circle of Willis produced
      normal results, whereas magnetic resonance imaging of the brain disclosed
      cortical signal abnormalities consistent with cytotoxic edema, without
      involvement of the adjacent white matter. Six-month follow-up magnetic resonance
      imaging of the brain indicated faint cortical atrophy in the same regions,
      although the neurologic picture had resolved. The literature contains few data on
      early magnetic resonance parenchymal changes, and their pathogenic mechanism is
      controversial. Diffusion-weighted images may contribute to an understanding of
      the mechanisms of such brain damage.

PMID- 19589470
TI  - A model in response to newborn screening mandates.

PMID- 19589468
TI  - Novel mutation of early, perinatal-onset, myopathic-type very-long-chain acyl-CoA
      dehydrogenase deficiency.
AB  - A male neonate demonstrated fetal distress, neonatal asphyxia, and transient
      hyper-creatine kinase-emia (8400IU/L), followed by repeated episodes of
      rhabdomyolysis 1-2 times/year during infancy and early childhood. At age 6 years,
      decreased levels of total and free carnitine in serum, and mild fiber size
      variation and increased fatty droplets in muscle, were confirmed. Both blood and
      serum fatty-acid analysis demonstrated elevated 5-tetradecenoate levels, and the
      acyl-CoA dehydrogenase activity of the palmitoyl-CoA/octanoyl-CoA ratio decreased
      in skin fibroblasts. The sequenced clone analysis of a complimentary DNA fragment
      revealed a compound heterozygote mutation of exon 9 (A790G) and exon 10 (997 ins
      T), which is a novel mutation of a myopathic-type very-long-chain acyl-CoA
      dehydrogenase deficiency. The patient has reached age 13 years. By treatment with
      an avoidance of fasting, feeding with a high-carbohydrate and low-fat diet, and
      intravenous drip infusion soon after every onset of rhabdomyolysis, his physical
      and mental development has stayed within the normal range. Patients with a
      perinatal onset of myopathic-type very-long-chain acyl-CoA dehydrogenase
      deficiency have not yet been reported. His novel mutation might be related to his
      clinical characterization.

PMID- 19589471
TI  - An evaluation of a Medicaid expansion for cancer care: The Breast and Cervical
      Cancer Prevention and Treatment Act of 2000.
AB  - The National Breast and Cervical Cancer Early Detection Program is a
      multifaceted, federal program that provides breast and cervical cancer screening
      and diagnostic services to low-income women, but does not cover the costs of
      treatment. This study used a fixed-effects, longitudinal time-series research
      design (from 1995 to 2005) to evaluate the impact of a Medicaid expansion aimed
      at covering treatment for program clients, enacted via the Breast and Cervical
      Cancer Prevention and Treatment Act of 2000. In summary, the Treatment Act of
      2000 had some positive impacts, including a 12.8% decrease in the average number
      of days to definitive cervical diagnosis for White women. Nonetheless, the
      Treatment Act also had some negative impacts on the timing of diagnosis and
      treatment services, including a significant increase in the average time between
      a diagnosis of cervical dysplasia or cancer and the initiation of treatment for
      Black and Hispanic women (7-15 days across age groups). The Treatment Act was
      also associated with a 9% decrease in the probability that Black women would
      initiate treatment within 60 days of a cervical diagnosis (-.094; 95% confidence
      interval [CI] -.178 to -.01). As such, although the Treatment Act had no impact
      on the proportion of clients who initiated breast cancer treatment within 60
      days, it reduced the probability that Black women initiated cervical treatment
      within an accepted benchmark for timely care.

PMID- 19589473
TI  - Prevalence and correlates of current depressive symptomatology and lifetime
      diagnosis of depression in Black women.
AB  - BACKGROUND: There is a paucity of research on depressive symptoms and their
      correlates among Black women, which may contribute to underdiagnosis,
      misdiagnosis, and inappropriate treatment. METHODS: Data were analyzed from the
      2006 Behavioral Risk Factor Surveillance System, an ongoing, state-based, random
      digit-dialed telephone survey of the noninstitutionalized U.S. population aged >
      or =18 years. A total of 10,783 Black women aged 18 to 64 years were interviewed
      from 38 states, 2 U.S. territories, and the District of Columbia (DC). There were
      8,412 (78.0%) women who provided complete responses to questions regarding
      demographic characteristics, psychosocial variables, current depressive
      symptomatology, and a lifetime diagnosis of a depressive disorder. Weighted
      prevalence estimates and 95% confidence limits of current depressive
      symptomatology and self-reported lifetime diagnosis of depression were derived.
      Multiple logistic regression models were used to examine the association of each
      correlate with the depression outcomes. RESULTS: Overall, 13.8% of Black women
      reported current depressive symptoms, and 14.9% reported a lifetime diagnosis of
      a depressive disorder by a health care provider. Significant correlates of both
      outcomes included rarely/never receiving social support, being unable to work,
      having physical health problems for 14 or more days in the past month, and
      dissatisfaction with life. CONCLUSIONS: This study indicates that a substantial
      number of Black women suffer from significant symptoms of depression and report
      that they have been diagnosed with depressive disorders in their lifetime. Health
      care providers should assess Black women with poor physical health and life
      dissatisfaction for depressive disorders and not dismiss somatic complaints as
      solely physically based.

PMID- 19589474
TI  - Care provided in visits coded for intimate partner violence in a national survey
      of emergency departments.
AB  - PURPOSE: This article describes the health status of and care provided to
      patients in visits coded to intimate partner violence (IPV) victims in a national
      survey of emergency departments (EDs). Visits coded for IPV were defined by
      International Classification of Diseases, 8th edition-Clinical Modification (ICD
      9-CM) codes. METHODS: Data from the National Hospital Ambulatory Medical Care
      Survey for 1997-2001 were analyzed. The sample consisted of 111 ED visits with
      ICD codes for IPV (or 12 IPV visits per 10,000 ED visits, and 21 female IPV
      visits per 10,000 female ED visits). FINDINGS: The majority of visits coded to
      IPV were for patients who presented with mild to moderate pain (86%), physical or
      sexual violence (50%), and injuries to the body (38%). The majority of patients
      in visits coded to IPV received radiologic testing, wound care, and pain
      medications (odds ratios [ORs], 1.6, 3.3, and 2.3 respectively). Disposition was
      mostly referral to another physician or clinic (42%) or return to the ED when
      needed (20%), but much less to nonphysician services such as social services,
      support services, and shelters (14%). Uninsured IPV patients were more likely to
      receive radiologic testing and pain medications (ORs 5.1 and 3, respectively).
      Patients seen by nurses were 9 times more likely to receive wound care.
      CONCLUSION: Caution should be exercised when interpreting the study results
      because they reflect only coded IPV visits in the ED and these might be the most
      obvious IPV cases. The results signal the need for further studies to evaluate
      access to and the quality of care for IPV patients and to improve screening,
      documentation, coding, and management practices.

PMID- 19589472
TI  - Disparities in detection and treatment history among mothers with major
      depression in Los Angeles.
AB  - OBJECTIVE: We sought to determine disparities in detection and treatment
      histories among a group of racial and ethnically diverse mothers with major
      depression. METHOD: Our sample included 276 racially and ethnically diverse
      mothers who participated in the Los Angeles Family and Neighborhood Survey and
      who were classified with major depression based on the Comprehensive
      International Diagnostic Interview-Short Form. We used logistic regression to
      assess the association between demographic factors and previous detection with
      major depression, mental health specialty use, and the use of a primary care
      physician among these women. The demographic factors examined included race and
      ethnicity, immigration status, marital status, education, income, body mass index
      (BMI), maternal age, number of children, children's ages, history of emotional
      problems, and history of diabetes. RESULTS: Results indicated that 69% of mothers
      had not been previously detected with major depression nor had they sought mental
      health treatment in the 12 months before the interview. The odds of having been
      previously diagnosed with major depression were significantly higher among White
      and single mothers, as well as among mothers with higher BMIs and those with a
      history of emotional problems. Nonimmigrant mothers without emotional problems
      had a higher odds of having seen a mental health specialist in the 12 months
      before the interview compared with immigrant mothers without emotional problems;
      no differences in mental health treatment were found between nonimmigrant and
      immigrant mothers with emotional problems. Finally, African-American mothers and
      those with a history of diabetes had significantly higher odds of seeing a
      primary care physician compared with Hispanic mothers and those with no history
      of diabetes, respectively. CONCLUSION: Our analyses of a population of depressed
      mothers living in Los Angeles highlight the need for identification and treatment
      of racial minority and immigrant mothers.

PMID- 19589475
TI  - Utilization of home pregnancy testing among women at risk for unintended
      pregnancy.
AB  - PURPOSE: We sought to determine whether a brief intervention increased home
      pregnancy test utilization among women at risk for unintended pregnancy. METHODS:
      The intervention included education, consultation with a nurse, and the provision
      of a free home pregnancy test kit. Participants were 35 women aged 18-39 years
      from a Medicaid population who were having unprotected intercourse and who were
      not trying to conceive. The women received education on pregnancy testing and the
      importance of early recognition of pregnancy. All women received a free home
      pregnancy test kit. The main outcome measures were pregnancy test use and
      appropriateness of use. MAIN FINDINGS: During the 3-month follow-up period, 62%
      of participants used the home pregnancy test kit, which was approximately 3 times
      higher than the self-reported testing rate before the study (p < .001). The most
      common reason for use was a late period (median 5 days late when test was done).
      Women also purchased additional kits to confirm the initial test result (median 2
      kits per episode of use). CONCLUSION: The intervention increased utilization of
      home pregnancy test kits among women at risk of unintended pregnancy. All study
      participants used the test appropriately. These results can serve as a framework
      for interventions to improve early pregnancy recognition.

PMID- 19589476
TI  - Reasons why women do not initiate breastfeeding: A southeastern state study.
AB  - PURPOSE: Despite the increase in breastfeeding initiation and duration in the
      United States, only five states have met the three Healthy People 2010
      breastfeeding objectives. Our objectives are to study women's self-reported
      reasons for not initiating breastfeeding and to determine whether these reasons
      vary by race/ethnicity, and other maternal and hospital support characteristics.
      METHODS: Data are from the 2000-2003 Arkansas Pregnancy Risk Assessment
      Monitoring System, restricting the sample to women who did not initiate
      breastfeeding (unweighted n=2,917). Reasons for not initiating breastfeeding are
      characterized as individual reasons, household responsibilities, and
      circumstances. Analyses include the chi(2) test and multiple logistic regression.
      RESULTS: About 38% of Arkansas mothers of live singletons did not initiate
      breastfeeding. There was a greater representation of non-Hispanic Blacks among
      those who did not initiate breastfeeding (32%) than among those who initiated
      breastfeeding (9.9%). Among those who never breastfed, individual reasons were
      most frequently cited for noninitiation (63.0%). After adjusting for covariates,
      Hispanics had three times the odds of citing circumstances than Whites (odds
      ratio [OR], 3.07; 95% confidence interval [CI], 1.31-7.18). Women who indicated
      that the hospital staff did not teach them how to breastfeed had more than two
      times greater odds of citing individual reasons (OR, 2.25; 95% CI, 1.30-3.91) or
      reasons related to household responsibilities (OR, 2.27; 95% CI, 1.19-4.36) as
      compared with women who indicated they were taught. CONCLUSIONS: Findings suggest
      the need for targeting breastfeeding interventions to different subgroups of
      women. In addition, there are implications for policy particularly regarding
      breastfeeding support in hospitals.

PMID- 19589478
TI  - Role of high-dose chemotherapy and autologous hematopoietic cell transplantation
      in primary systemic amyloidosis: a systematic review.
AB  - Significant uncertainty exists regarding the efficacy of high-dose chemotherapy
      and autologous hematopoietic cell transplantation (AHCT) for the treatment of
      patients with primary systemic (AL) amyloidosis. We performed a systematic review
      and meta-analysis to evaluate the efficacy of AHCT versus conventional
      chemotherapy (CC) in patients with AL amyloidosis using methodology recommended
      by the Cochrane Collaboration. A comprehensive literature search yielded 820
      studies. Twelve studies met the inclusion criteria: 1 randomized controlled trial
      (RCT), 2 other controlled studies, and 9 single-arm trials. The 1 RCT and 2
      controlled studies compared AHCT and CC, and 9 single-arm studies assessed the
      efficacy of AHCT without a control. The pooled hazard ratio for overall survival
      (OS) in the 3 controlled studies was 1.79 (95% confidence interval [CI] = 1.11 to
      2.91) favoring CC. The pooled proportion for mortality in the single-arm studies
      (n = 7) was 0.35 (95% CI = 0.25 to 0.46). The pooled odds ratio for complete
      hematologic response (CHR) from 2 controlled studies was 0.64 (95% CI = 0.25 to
      1.64), indicating no difference between AHCT and CC. In the single-arm studies,
      the pooled proportion for CHR was 0.35 (95% CI = 0.26 to 0.44), and the pooled
      proportion for treatment-related mortality (TRM) was 0.12 (95% CI = 0.09 to
      0.14). In the controlled studies, there was no heterogeneity for any outcome;
      however, in the single-arm studies, there was a significant heterogeneity for the
      outcomes of OS, CHR, renal response, and partial hematologic response. Our
      findings indicate that AHCT does not appear to be superior to CC in improving OS
      in patients with AL amyloidosis. But the quality of our evidence is low,
      indicating a need for well-designed and adequately powered RCTs to better address
      the role of AHCT in AL amyloidosis.

PMID- 19589477
TI  - HIV testing among sexually experienced Asian and Pacific Islander young women
      association with routine gynecologic care.
AB  - PURPOSE: To describe the proportion of HIV testing in the past 12 months among
      sexually experienced Asian and Pacific Islander (API) women and to investigate to
      what extent routine gynecologic care (RGC) increases HIV testing among API women.
      METHODS: Data were derived from Wave III of the National Longitudinal Study of
      Adolescent Health (Add Health). Analyses were limited to 7,576 sexually
      experienced women (White, n = 4,482 [68.5%]; Black, n = 1,693 [25.6%]; Hispanic,
      n = 923 [13.9%]; API, n = 478 [7.2%]) aged 18-27 years. Multiple logistic
      regression analyses were used to estimate the association between RGC and HIV
      testing after controlling for predisposing, need, and enabling factors. FINDINGS:
      On average, 22.8% (n = 1,504) of sexually experienced women reported HIV testing
      in the past year. API women had the lowest proportion of testing (17.2%), and
      Black women had the highest (26.2%). Overall, 60.2% of API women reported
      receiving RGC; however, only 15.5% of API who received RGC reported HIV testing.
      After controlling for covariates, significantly positive associations were found
      for White, Black, and Hispanic women between RGC and HIV testing; however, there
      was no evidence that RGC was associated with HIV testing among API women.
      CONCLUSION: Our data suggest that RGC does not [corrected] increase HIV testing
      among API women. To eliminate disparities in HIV testing service utilization
      among API women, appropriate efforts should be directed to better understand the
      barriers and facilitators of HIV testing among this population.

PMID- 19589479
TI  - Methodological and logistical considerations to study design and data collection
      in racial/ethnic minority populations evaluating outcome disparity in
      hematopoietic cell transplantation.
AB  - Outcome disparity associated with race or ethnicity in the United States has been
      observed in hematopoietic cell transplantation (HCT). The underlying reasons for
      such disparity are not known. In the United States, an optimal study of health
      care disparity by race or ethnicity involves consideration of both biologic and
      psychosocial determinants, which requires an adequately powered, prospective
      cohort study design. To better characterize the nature and quantify the magnitude
      of the many impediments relevant to conducting a successful prospective study
      involving racial or ethnic minorities in HCT, we conducted a feasibility study to
      help guide planning of a larger scale outcome and disparity study in HCT. The
      primary questions to be addressed in the study were: (1) can we establish a
      racially or ethnically diverse patient sample that will respond to a survey
      focused on sociodemographic, economic, health insurance, cultural, spiritual, and
      religious well-being, and social support information? (2) What is the retention
      rate in the study over time? (3) What is the quality of the data collected from
      the patients over time? The challenges we faced in conducting this multicenter
      feasibility study are summarized in this report. Despite the difficulty in
      conducting disparity studies in racial and ethnic minorities, such studies are
      essential to ensure that people of all ethnic and racial backgrounds have the
      best chance possible of benefiting from HCT.

PMID- 19589480
TI  - Successful treatment of severe acute intestinal graft-versus-host resistant to
      systemic and topical steroids with alemtuzumab.
AB  - Development of severe steroid-resistant acute graft-versus-host disease (GVHD)
      after allogeneic hematopoietic cell transplantation (HCT) is associated with poor
      outcome. The humanized monoclonal antibody alemtuzumab was shown to be effective
      in GVHD prophylaxis in conditioning regimens before allogeneic HCT. We evaluated
      the efficacy and safety of alemtuzumab in 20 patients with histologically
      confirmed steroid refractory grade III and IV intestinal GVHD after related and
      unrelated HCT. Overall response rate was 70%, with complete response in 35%.
      Despite the severe grade of GVHD in our patients, the median survival of 280 days
      and 1-year overall survival (OS) of 50% were superior or comparable to those
      associated with other treatment options. Cytomegalovirus (CMV) reactivation,
      bacterial infection, and invasive aspergillosis were frequent complications;
      however, infection was not a significant predictor for survival. These data
      suggest that treatment with alemtuzumab has favorable activity in severe
      intestinal GVHD after allogeneic HCT, but emphasize the importance of careful
      monitoring and anti-infectious supportive care.

PMID- 19589481
TI  - Graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil
      in HLA-matched nonmyeloablative transplant recipients is associated with very low
      incidence of GVHD and nonrelapse mortality.
AB  - Incidence of grade II-IV acute graft-versus-host disease (aGVHD) in
      nonmyeloablative (NMA) transplant recipients remains high. To date, the ideal
      prophylaxis regimen, which minimizes aGVHD and chronic GVHD (cGVHD), but does not
      abrogate graft-versus-tumor (GVT) response, has not been described. Because
      tacrolimus is more potent than cyclosporine (CSA), and because mycophenolate
      mofetil (MMF) is an effective immunosuppressant that does not lead to mucositis,
      we hypothesized that a combination of these 2 oral agents may be an effective
      GVHD prophylactic strategy. We, therefore, designed an outpatient prospective
      cohort study with a conditioning regimen consisting of fludarabine (Flu) 30 mg/m2
      daily and cyclophosphamide (Cy) 300 mg/m2 daily for 5 days followed by infusion
      of blood stem cells. Tacrolimus 3mg twice a day was started on day (D) -8,
      adjusted to achieve levels 10-15 nmol/L, continued until D +50 and then tapered
      by D +100 or +180 according to estimated risk of relapse. MMF 1000 mg twice a day
      was started on D +1 and discontinued on D +50. To date, 131 patients
      (males/females: 75/56) with a median age of 54 years have received a 6/6 matched
      sibling transplant using this protocol. Indication for NMA transplant included
      age >55 years (24%), expected increased risk of toxicity (28%), or participation
      in a multiple myeloma (MM) sequential protocol (48%). Most common diagnoses
      included MM (N = 62), non-Hodgkin lymphoma (NHL, N = 46), and acute leukemia (N =
      10). Following infusion of 6.8 x 10(6) CD34+ cells/kg (range: 0.30-22.3),
      neutrophil and lymphocyte engraftment occurred in 95% of patients by D +180. The
      estimated cumulative incidence of classical grade I-IV aGVHD by D +120 was 11.6%
      (95% confidence interval [CI]: 7.1-18.5). No grade IV aGVHD was observed. In
      addition, 15 patients (12%: CI: 7.4-19.2; median D +140) developed an overlap
      syndrome consisting of clinical and histologic features of both aGVHD and cGVHD
      simultaneously. The estimated cumulative incidence of extensive cGVHD was 76.1%
      (95% CI: 67.4-83.9) at 2 years, with clinical features at presentation similar to
      other reported series. In patients developing extensive cGVHD, the probability of
      remaining on immunosuppression at 5 years was 34.8% (95% CI: 16.4-57.3). With a
      median follow-up of 982 days, the estimated probabilities of nonrelapse mortality
      (NRM) and overall survival (OS) were 15.5% (95% CI: 9.0-26.1) and 62.7% (95% CI:
      51.4-72.1). The cumulative incidence of relapse was 30% at 7 years. Following NMA
      transplant, disease-free survival (DFS) was highest in recipients with follicular
      NHL (79.8%: 95% CI: 57.6-91.2) and lowest in large cell NHLs (34.3%: 95% CI: 1.6
      75.9). From this large group of patients treated with a uniform conditioning and
      GVHD prophylaxis regimen, we conclude that aGVHD prophylaxis with early use of
      tacrolimus and MMF is safe, effective, and associated with low NRM. Future
      strategies will need to focus on decreasing the incidence of extensive cGVHD
      without increasing the risk of relapse.

PMID- 19589482
TI  - A modified haploidentical nonmyeloablative transplantation without T cell
      depletion for high-risk acute leukemia: successful engraftment and mild GVHD.
AB  - Severe graft-versus-host disease (GVHD) and graft rejection still remain major
      complications of haploidentical nonmyeloablative (NMA) stem cell transplantation.
      Recent studies have shown that bone marrow-derived mesenchymal stem cells (MSCs)
      possess immunomodulatory capacity and may promote hematopoietic engraftment. The
      purpose of this study was to observe if the new strategy, which included a
      haploidentical peripheral blood stem cell transplantation (PBSCT) combined with
      MSCs, modified NMA conditioning, and GVHD prophylaxis would improve donor
      engraftment and prevent severe GVHD. The modified conditioning approach consisted
      of fludarabine (Flu), low-dose total body irradiation (TBI), cyclophosphamide
      (Cy), cytarabine, and anti-Tcell-lymphocyte globulin, whereas the GVHD
      prophylaxis consisted of cyclosporin A (CsA), mycophenolate mofetil (MMF), anti
      CD25 antibody and intrabone marrow injection of MSCs. Thirty-three patients with
      high-risk acute leukemia underwent transplantation with PBSC from HLA
      haploidentical donors without T cell depletion. All of the patients achieved full
      donor chimerisms, including 6 who switched to full donor chimerisms from mixed
      chimerisms in 1 to 2 months after the transplantations. Rapid hematological
      engraftment was observed with neutrophils >0.5 x 10(9)/L at day 11 and platelets
      >20 x 10(9)/L at day 14. Fifteen patients (45.5%) developed grade I-IV acute GVHD
      (aGVHD) and only 2 (6.1%) developed grade III to IV aGVHD. Nine (31%) of 29
      evaluable patients experienced chronic GVHD (cGVHD). Upon follow-up for 1.5 to 60
      months, 20 (60.6%) patients were alive and well and 6 (18.2%) had relapsed
      leukemia in the 33 patients. The probability of 3-year survival was 57.2%. The
      results indicate that this new strategy is effective in improving donor
      engraftment and preventing severe GVHD, which will provide a feasible option for
      the therapy of high-risk acute leukemia.

PMID- 19589483
TI  - Increase in FOXP3+ regulatory T cells in GVHD skin biopsies is associated with
      lower disease severity and treatment response.
AB  - In animal models, CD4+/CD25+ T-regulatory cells (Tregs) have been reported to
      prevent/delay the onset of graft-versus-host disease (GVHD). Recently, an
      insufficient upregulation of Tregs was found in target organ (intestinal)
      biopsies from patients with GVHD. We have analyzed by immunohistochemistry the
      number of CD3+ T lymphocytes and FOXP3+ Tregs in skin biopsies from (1)
      recipients of allogeneic hematopoietic stem cell transplantation (HSCT, n = 26),
      (2) nontransplanted patients diagnosed with cutaneous drug reaction (n = 12), and
      (3) healthy donors (n = 10). Infiltrating CD3+ cells were significantly higher in
      both transplanted patients showing acute GVHD (aGVHD) and drug reaction when
      compared to healthy donors and patients without GVHD. Tregs number in aGVHD was
      higher than in patients without GVHD or healthy subjects and lower than in drug
      reaction. Interestingly, the number of infiltrating FOXP3+ Tregs was
      significantly higher in patients responding to GVHD treatment and with a low GVHD
      grade. Increase in FOXP3+ Tregs in GVHD skin biopsies correlates with less severe
      GVHD and is associated with response to GVHD treatment. Larger studies are
      required to confirm that evaluation of Tregs in minimally invasive skin biopsies
      assists the diagnosis and prognosis of GVHD patients.

PMID- 19589484
TI  - Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic
      syndrome: a single-center experience.
AB  - Myelodysplastic syndromes (MDS) respond poorly to chemotherapy. Between 1995 and
      2006, 23 pediatric patients with MDS were transplanted with unrelated donor
      umbilical cord blood (UUCB) at our center. The median age was 11.1 years (range:
      1.1-19.7), median weight was 38.6 kg (range: 9.6-62.6), 61% of patients were
      male, and median time from diagnosis to transplant was 6.6 months (range: 2.0
      61.4). Patients were followed for a median of 5.3 years (range: 1.6-12.4 years)
      posttransplant. MDS stage was refractory anemia (RA) in 12, refractory anemia
      with excess blasts (RAEB) in 8, and refractory anemia with excess blasts in
      transformation (RAEB-T) in 3 patients; 18 (78%) patients had primary MDS.
      Monosomy 7 was present in 17(74%) patients. Patients with acute myelogenous
      leukemia (AML) were excluded. Preparative regimen was total body irradiation
      (TBI) based in 18 (78%) patients. Graft-versus-host-disease (GVHD) prophylaxis
      was cyclosporine (CsA)/steroids (19 patients) or CsA/mycophenolate mofetil (MMF;
      4 patients). Grafts were HLA matched at Class I (A and B) at low resolution and
      Class II (DRB1) at the allelic level, resulting in 16 (70%) 4/6 and 7 (30%) 5/6
      matched transplants. The grafts contained a median of 4.0 x 10(7) (range: 1.7
      12.6) total nucleated cells (TNC)/kg precryopreservation; 3.6 x 10(7) (range: 1.0
      12.0) TNC/kg and 1.7 x 10(5) (range: 0.2-28.5) CD34+ cells/kg were infused.
      Cumulative incidence of neutrophil engraftment (absolute neutrophil count [ANC]
      >500/microL) at day 42 and day 100 was 73.9% (95% confidence interval [CI] 55.1%
      92.7%) and 91.3% (95% CI 71.3%-100.0%) respectively, and that of platelet
      engraftment (50 K) at 180 days was 69.6% (95% CI 49.8%-89.4%). Three patients had
      graft failure whereas 3 patients (13%) engrafted slowly (after day 42). Three
      patients developed acute GVHD (aGVHD) grades II-IV with a cumulative incidence at
      100 days of 13% (95% CI 0.0%-27.1.0%). Four patients relapsed with a cumulative
      incidence of relapse at 3 years of 13.0% (95% CI 0.0%-27.1%). Cumulative
      incidence of nonrelapse mortality (NRM) at 1 year was 27% (95% CI 8.0%-46.0%).
      Ten patients died: 3 graft failure, 4 relapse, 2 infections (1 adenovirus, 1
      toxoplasmosis), and 1 Epstein-Barr virus (EBV) lymphoproliferative disorder.
      Probabilities of event-free survival (EFS) at 1 and 3 years were 69.6% (95% CI
      46.6%-84.2%) and 60.9% (95% CI 38.3%-77.4%), respectively. Factors associated
      with better EFS were age < or = 11 years (P = .05) and weight < or = 38 kg (P =
      .03). These results, especially in younger patients with monosomy 7 positive MDS,
      are equivalent to published matched allogeneic bone marrow data. UUCB should be
      actively considered for pediatric MDS patients lacking matched related or
      unrelated adult donors.

PMID- 19589485
TI  - Clinical significance of serum hepcidin levels on early infectious complications
      in allogeneic hematopoietic stem cell transplantation.
AB  - The association of iron overload with complications of allogeneic hematopoietic
      stem cell transplantation (HSCT) has been suggested in previous studies. Because
      hepcidin plays a central role in the regulation of iron homeostasis, we analyzed
      the association between pretransplant serum hepcidin-25 levels and early
      infectious complications after allogeneic HSCT. We studied 55 consecutive adult
      patients with a median age of 47 years (range: 20-64 years) who underwent
      allogeneic HSCT for hematologic malignancies at our institution. Thirty-two
      patients had myelogenous malignancies; the remaining 23 had lymphogenous
      malignancies. The median pretransplant serum hepcidin level of patients in the
      study was 21.6 ng/mL (range: 1.4-371 ng/mL), which was comparable to that of
      healthy volunteers (median: 19.1 ng/mL [range: 2.3-37 ng/mL]; n = 17). When
      cumulative incidences of documented bacterial and cytomegalovirus (CMV)
      infections at day 100 were compared according to pretransplant hepcidin-25
      levels, the incidence of bacterial, but not CMV, infection, was significantly
      higher in the high-hepcidin group (> or = 50 ng/mL; n = 17) than in the low
      hepcidin group (<50 ng/mL; n = 38) (65% [95% confidence interval, 38%-82%] versus
      11% [3%-23%]; P < .001). This finding was confirmed by multivariate Cox analysis
      adjusted for confounders, including pretransplant ferritin and C-reactive protein
      (CRP) levels. No fungal infection was documented in either group. These results
      suggest that the pretransplant serum hepcidin-25 level may be a useful marker for
      predicting the risk of early bacterial complications after allogeneic HSCT.
      Larger prospective studies are, however, warranted to confirm our findings.

PMID- 19589486
TI  - Strategies to improve long-term outcome in stage IIIB inflammatory breast cancer:
      multimodality treatment including dose-intensive induction and high-dose
      chemotherapy.
AB  - Inflammatory breast cancer (IBC) is a rare clinicopathologic entity with a poor
      prognosis, lagging far behind any other form of nonmetastatic breast cancer.
      Since the advent of systemic chemotherapy over 35 years ago, only minimal
      progress has been made in long-term outcome. Although multiple randomized trials
      of high-dose chemotherapy and autologous progenitor cell transplantation (ASCT)
      for the treatment of breast cancer have yielded disappointing results, these data
      are not necessarily relevant to IBC, a distinct clinical and pathologic entity.
      Therefore, the optimal multimodality therapy for IBC is not well established, and
      remains unsatisfactory. We treated 21 women with nonmetastatic IBC with a
      multimodality strategy including high-dose melphalan (Mel)/etoposide and ASCT.
      The treatment was overall tolerated with acceptable morbidity, and no post-ASCT
      100-day mortality. With a median potential follow-up of approximately 8 years,
      the estimated progression-free survival (PFS), event-free survival (EFS), and
      overall survival (OS) at 6 years from on-study date are: 67%, 55%, and 69%,
      respectively. These results from a small phase II study are among the most
      promising of mature outcome data for IBC. They strongly suggest, along with
      results of several already published phase II trials, that ASCT could play a
      significant role in the first line treatment of IBC.

PMID- 19589488
TI  - A meta-analysis of patients receiving allogeneic or autologous hematopoietic stem
      cell transplant in mycosis fungoides and Sezary syndrome.
AB  - The survival outlook in advanced mycosis fungoides (MF) is poor. Autologous and
      allogeneic stem cell transplants (SCT) have been shown, in small case series and
      case reports, to have the potential for long-term remission or to alter disease
      course. Allogeneic SCT is thought to have a curative potential secondary to a
      graft-versus-lymphoma (GVL) effect. A patient-level meta-analysis was performed
      to compare the outcome of allogeneic versus autologous SCT in patients with
      MF/Sezary syndrome (SS) using 39 cases from the literature. There were a total of
      20 allogeneic and 19 autologous transplant cases. The gender, age, and stage
      distribution was similar between the transplant groups. The allogeneic group
      received significantly more systemic therapies prior to transplant (P < .0005)
      and had longer follow-up after transplant. Overall survival (OS) results showed a
      more favorable outcome of patients who received allogeneic SCT (P = .027). Event
      free survival (EFS) demonstrated a more durable response in patients who received
      allogeneic SCT (P = .002). In the allogeneic group, the majority (70%) of
      patients experienced persistent graft-versus-host disease (GVHD), mostly with
      mild to moderate severity, and 2 of 4 deaths were related to GVHD. Meanwhile, the
      majority of the deaths (8 of 10) in the autologous group were because of
      progressive disease. These results support the belief that allogeneic SCT offers
      a better survival and disease-free outcome versus autologous SCT in MF/SS, likely
      because of a GVL effect.

PMID- 19589487
TI  - HLA-A disparities illustrate challenges for ranking the impact of HLA mismatches
      on bone marrow transplant outcomes in the United States.
AB  - HLA disparity between hematopoietic stem cell donors and recipients is one of the
      most important factors influencing transplant outcomes, but there are no well
      accepted guidelines to aid in selecting the optimal donor among several HLA
      mismatched donors. In this report, HLA-A is used as a model to illustrate factors
      that are barriers to delineating the relationship between specific HLA mismatches
      and transplant outcomes in the United States. Patients in this investigation
      received transplants for hematologic malignancies that were facilitated by the
      National Marrow Donor Program (NMDP) between 1990 and 2002 (n = 4226). High
      resolution HLA typing was performed for HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, 
      DPA1, and -DPB1. HLA-A mismatches were observed in 745 donor-recipient pairs and
      62% of these pairs also had disparities at HLA-B, -C, and/or -DRB1. The HLA-A
      mismatches involved 190 different combinations of HLA-A alleles and 51% of these
      were observed in only 1 pair. Addition of a single HLA-A disparity when HLA-B, 
      C, and -DRB1 were matched (n = 282) was associated with increased mortality (odds
      ratio [OR] = 1.32, confidence interval [CI] 1.07-1.63). When HLA-B, -C, and -DRB1
      were matched, the most frequent HLA-A mismatches were HLA-A*0201:0205 (n = 28),
      HLA-A *0301:0302 (n = 15), HLA-A *0201:0206 (n = 15), HLA-A *0201:6801 (n = 12),
      HLA-A*0101:1101 (n = 11), and HLA-A*0101:0201 (n = 10). There were no
      statistically significant relationships between any of these disparities and
      transplant outcomes (engraftment, acute and chronic graft-versus-host disease
      [aGVHD, cGVHD] relapse, treatment-related mortality [TRM], or overall survival
      [OS]) when adjustments for multiple comparisons were considered. Achieving 80%
      power to detect an effect of any 1 of these 6 HLA-A disparities on survival is
      estimated to require a total transplant population of 11,000 to more than 1
      million U.S. donor-recipient pairs depending upon the HLA disparity. Thus,
      alternative approaches are required to develop a clinically relevant ranking
      system for specific HLA disparities in the United States.

PMID- 19589490
TI  - Low serum levels of total rabbit-IgG is associated with acute graft-versus-host
      disease after unrelated donor hematopoietic stem cell transplantation: results
      from a prospective study.
AB  - In a prospective study we determined rabbit-IgG (r-IgG) levels in serum samples
      before (day 0) and after (days 1 and 7) unrelated donor hematopoietic stem cell
      transplantation (HSCT). Most patients suffered from a hematologic malignancy. All
      patients received rabbit antithymocyte globulin (ATG) as part of the conditioning
      for 2-4 days (2 mg/kg/day). We found a good correlation (r = 0.34, r = 0.42 and r
      = 0.46) between the dose of ATG and serum r-IgG levels at all 3 time points. The
      cumulative incidence of acute graft-versus-host disease (aGVHD) grades II-IV in
      patients given the 4, 6, and 8 mg/kg ATG dose was 50%, 34%, and 15% (P = .04),
      respectively. In patients with r-IgG < or = 70 microg/mL (n = 54) the cumulative
      incidence of grades II-IV aGVHD was 33% compared with only 6% in those with r-IgG
      >70 microg/mL (n = 18), P = .023. Low serum levels of r-IgG seem to be a strong
      predictor for aGVHD grades II-IV in patients treated with Thymoglobulin before
      unrelated donor HSCT.

PMID- 19589491
TI  - Difficulties in monitoring the glucose status of patients undergoing
      hematopoietic stem cell transplantation.

PMID- 19589492
TI  - 59-year-old man with MDS.

PMID- 19589489
TI  - Fatal rhizopus pneumonia in allogeneic stem cell transplant patients despite
      posaconazole prophylaxis: two cases and review of the literature.
AB  - Posaconazole is a triazole with broad spectrum of activity against multiple fungi
      including members of the fungal order Mucorales. This activity has been shown
      both in clinical and in vitro studies, which are critically reviewed here. It has
      become very popular in prophylaxis in acute myelogenous leukemia (AML) induction
      and in the graft-versus-host disease (GVHD) settings after 2 recent prospective
      trials that showed advantage of posaconazole prophylaxis compared to fluconazole
      or itraconazole. In this report, 2 patients are presented, in whom, despite
      posaconazole prophylaxis, invasive and ultimately fatal Rhizopus pulmonary
      infections developed. These cases are similar to a previously reported case of
      Rhizopus infection in a stem cell transplant recipient who also received
      posaconazole, indicating a potential newly recognized pattern of breakthrough
      infections in patients receiving posaconazole prophylaxis.

PMID- 19589493
TI  - Diagnostic ability of Fourier-domain vs time-domain optical coherence tomography
      for glaucoma detection.
AB  - PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness assessments and
      the discriminating ability of Fourier-domain optical coherence tomography (FD
      OCT) with that of time-domain optical coherence tomography (TD-OCT) for glaucoma
      detection. DESIGN: Prospective, nonrandomized, observational cohort study.
      METHODS: Normal and glaucomatous eyes underwent complete examination, standard
      automated perimetry, optic disc photography, TD-OCT (Stratus OCT; Carl Zeiss
      Meditec, Dublin, California, USA), and FD-OCT (RTVue; Optovue Inc, Fremont,
      California, USA). One eye per subject was enrolled. Two consecutive scans were
      acquired using a 3.46-mm diameter scan with TD-OCT and a 3.45-mm diameter scan
      with FD-OCT. For each of 5 RNFL parameters, the area under the receiver operator
      characteristic curve was calculated to compare the ability of FD-OCT and TD-OCT
      to discriminate between normal and glaucomatous eyes. RESULTS: Fifty healthy
      persons (mean age, 65.3 +/- 9.9 years) and 50 glaucoma patients (mean age, 67.7
      +/- 10.5 years) were enrolled. Average, superior, and inferior RNFL thickness
      measurements (in micrometers) were significantly (P < .01) greater with FD-OCT
      compared with TD-OCT in normal eyes (103.3 +/- 12.6 vs 96.3 +/- 10.7, 134.5 +/-
      18.6 vs 113.9 +/- 16.3, and 129.7 +/- 16.9 vs 125.5 +/- 15.8, respectively) and
      glaucomatous eyes (P < .001; 77.6 +/- 17.6 vs 70.4 +/- 18.6, 108.0 +/- 26.8 vs
      86.8 +/- 30.2, 82.2 +/- 3.3 vs 73.5 +/- 26.1, respectively). The area under the
      receiver operator characteristic curves for RNFL thickness were similar (P > .05)
      using FD-OCT (average, 0.88; superior, 0.80; inferior, 0.94) and TD-OCT (average,
      0.87; superior, 0.79; inferior, 0.95). CONCLUSIONS: Cross-sectional peripapillary
      RNFL thickness measurements obtained using FD-OCT generated with the RTVue are
      greater than those obtained with TD-OCT and have similar diagnostic performance
      for glaucoma detection.

PMID- 19589494
TI  - Effect of slow-releasing all-trans-retinoic acid in bioabsorbable polymer on
      delayed adjustable strabismus surgery in a rabbit model.
AB  - PURPOSE: To determine the usefulness of slow-releasing all-trans-retinoic acid
      (ATRA) in polytetrafluoroethylene (PTFE)/polylactide-co-glycolide (PLGA) for
      delayed adjustable strabismus surgery. DESIGN: Animal study. METHODS: A
      prospective, masked-observer, controlled study was performed in 25 rabbits. Fifty
      rabbit eyes were divided randomly into three groups. After a recession of the
      superior rectus muscle, a PTFE/PLGA laminate containing ATRA, PTFE alone, or
      balanced salt solution was applied beneath and over the superior rectus muscle in
      the PTFE/PLGA/all-trans-retinoic acid group (ATRA group), the
      polytetrafluoroethylene group (PTFE group), and the control group, respectively.
      Delayed adjustment was performed once on each superior rectus muscle at 3 or 5
      weeks after surgery by a masked observer. RESULTS: In the control group,
      adjustment was possible in 2 of 5 eyes at 3 weeks after surgery and impossible in
      any eye at 5 weeks after surgery. In the PTFE and ATRA groups, adjustment was
      possible in all 10 eyes at 3 and 5 weeks after surgery. On comparing
      adjustability, a significant difference was observed between the PTFE group and
      the control group or between the ATRA group and the control group 5 weeks after
      surgery (P = .0003 and P = .0003, respectively). A significant difference was
      observed between the ATRA group and the control group in terms of adhesion
      between superior rectus muscles and sclerae at 5 weeks after surgery (P = .006).
      CONCLUSIONS: Slow-releasing ATRA in PTFE/PLGA was found to reduce adhesion and to
      allow delayed adjustment in most eyes for up to 5 weeks after surgery.

PMID- 19589495
TI  - Comparison of outcomes of lamellar keratoplasty and penetrating keratoplasty in
      keratoconus.
AB  - PURPOSE: To compare outcomes after penetrating keratoplasty (PK) and two
      techniques of deep anterior lamellar keratoplasty (DALK) in patients with
      keratoconus. DESIGN: Retrospective cohort study. METHODS: One hundred and twenty
      five corneal transplantations comprising 100 PK and 25 DALK procedures for
      keratoconus at the Singapore National Eye Centre from April 1992 through December
      2006 were included. DALK was performed with the modified Anwar technique
      (descemetic or DALKa group) in 14 eyes and manual lamellar keratoplasty
      (predescemetic or DALKm group) was performed in 11 eyes. RESULTS: At 12 months,
      the DALKa and PK groups achieved a logarithm of the minimum angle of resolution
      mean best spectacle-corrected visual acuity (BSCVA) of 0.15 and 0.27,
      respectively (P = .26), whereas the mean BSCVA of the DALKm group was 0.41
      compared with the PK group (P = .12). Significance level was achieved between the
      DALKa and DALKm groups (P = .013). There was no significant difference in the
      mean spherical equivalent (P = .72) and astigmatism (P = .88) between the PK and
      DALK groups. The DALK group had a significantly lower incidence of complications
      compared with PK cases, including allograft rejection and glaucoma. Graft
      survival rate of both the PK and DALKa groups was 100%, whereas that of the DALKm
      group was 73% at 3 years after surgery (P = .000 between PK and DALKm groups).
      CONCLUSIONS: Visual acuity outcomes of the DALKa technique are comparable with
      those of PK for keratoconus, whereas DALK surgery results in fewer postoperative
      complications than PK. DALKa is emerging as a preferred choice among the lamellar
      techniques for better optical outcome. Further studies are required to provide
      long-term analysis of these results.

PMID- 19589496
TI  - Evaluation of scleral buckling for stage 4A retinopathy of prematurity by
      fluorescein angiography.
AB  - PURPOSE: To determine the early efficacy of scleral buckling for active
      neovascularization by fundus fluorescein angiography (FA) in eyes with stage 4A
      retinopathy of prematurity. DESIGN: A retrospective, nonrandomized, observational
      case series. METHODS: Patients who underwent scleral buckling for stage 4A ROP at
      the National Center for Child Health and Development, Tokyo, Japan, from October
      2007 through November 2008 were included. Preoperative and postoperative FA and
      fundus photographs obtained with a wide-field digital pediatric imaging system
      were reviewed. Three patients (5 eyes; gestational ages at birth, 23 to 25 weeks;
      birth weights, 574 to 811 g) with zone II stage 4A ROP who underwent
      postoperative FA, 2 weeks or less after scleral buckling (range, 7 to 12 days;
      postmenstrual ages at postoperative FA, 41 to 45 weeks) were evaluated. Patients
      who underwent postoperative FA 2 weeks or more after scleral buckling were
      excluded. RESULTS: Despite fluorescein leakage from fibrovascular tissue in all
      eyes before surgery, markedly decreased leakage occurred only between 7 to 12
      days after surgery. The retinas were reattached completely in all eyes after
      surgery. CONCLUSIONS: Scleral buckling may prevent progression of retinal
      detachment in stage 4A ROP by reducing the tractional force and stabilizing the
      neovascular activity of the fibrovascular tissue.

PMID- 19589498
TI  - A survey of the optimal handle position for boxes with different sizes and manual
      handling positions.
AB  - Handles on objects are very important for enhancing the safety and efficiency of
      manual handling for people who use them. In this study, four different prototype
      boxes with auxiliary handles were designed to determine the optimal handle
      position of a box based on the evaluated user preferences and body part
      discomfort (BPD). Twenty male students participated in the experiment. Likert-5
      point summated rating was applied to evaluate user preferences for the provided
      boxes with handles in upper, middle, and lower positions, in four different sizes
      and manual handling positions. Ten additional subjects were asked to indicate
      their BPD on a body chart after performing a similar experiment. The results show
      that the subjects preferred the upper part of the handle on a small box
      regardless of handling position; while the mid to upper parts of the handle on a
      big box were preferred for handling above the waist height. BPD also indicated
      that an upper handle was less stressful for a relatively smaller box than a big
      one; and mid to upper handles were less comfortable for a big box. The optimal
      handle positions depending on box size and handling position were suggested based
      on the results of the evaluation. It is thus recommended that a box provides a
      handle according to its relevant position, depending on size and manual handling
      condition, to reduce the musculoskeletal stress and in turn to increase user
      satisfaction.

PMID- 19589497
TI  - Intravitreal bevacizumab vs sub-tenon triamcinolone acetonide for choroidal
      neovascularization attributable to pathologic myopia.
AB  - PURPOSE: To compare the visual outcomes of intravitreal bevacizumab (Avastin;
      Genentech Inc, South San Franciso, California, USA) and sub-Tenon triamcinolone
      acetonide (TA) for choroidal neovascularization attributable to pathologic myopia
      (mCNV). DESIGN: Retrospective, comparative, interventional case series. METHODS:
      Fifty-four consecutive eyes of 53 patients with mCNV treated with either sub
      Tenon TA or intravitreal bevacizumab in an institutional setting were included.
      Twenty eyes were treated with sub-Tenon TA and 34 eyes were treated with
      intravitreal bevacizumab. The main outcome measures included best-corrected
      visual acuity (BCVA) 12 months after the initial injection and logarithm of the
      minimum angle of resolution gain from baseline compared with analysis of
      covariance (ANCOVA). RESULTS: At 12 months, the BCVA improved by 1.9 lines in the
      intravitreal bevacizumab group and worsened by 0.3 lines in the sub-Tenon TA
      group. Thus, the intravitreal bevacizumab group had significantly greater visual
      improvement than the sub-Tenon TA group (P < .01). Statistical analysis (ANCOVA)
      revealed that age (P = .01), pretreatment BCVA (P < .01), and the treatment
      choice (intravitreal bevacizumab or sub-Tenon TA; P < .01) correlated
      significantly with the BCVA and the BCVA gain at 12 months. The refractive error
      was of borderline significance (P = .06). CONCLUSIONS: Although this study is
      limited because of its retrospective nature, intravitreal bevacizumab seems to
      result in a more favorable visual outcome than sub-Tenon TA in the treatment of
      mCNV. Patient age, the BCVA before treatment, and the refractive error must be
      considered to initiate the treatment.

PMID- 19589499
TI  - Development and validation of the Rasch-based Depression Screening (DESC) using
      Rasch analysis and structural equation modelling.
AB  - Questionnaires for the assessment of depression benefit from modern test
      construction like item-response-modelling. We developed two parallel 10 item
      depression questionnaires, the Rasch-based Depression Screening version 1 (DESC
      I) and 2 (DESC-II), by combining Rasch analysis and structural equation modelling
      on patient samples suffering primarily from a mental disorder or from somatic
      diseases. Both scales base upon a Rasch homogeneous item bank and proved
      unidimensionality and good model fit. Cut-off scores with good sensitivity and
      specificity were developed using ROC analyses. Results suggest that DESC may be
      appropriately used to screen for depression and may be beneficial for repeated
      measurements.

PMID- 19589500
TI  - Metacognitions as a predictor of drinking status and level of alcohol use
      following CBT in problem drinkers: a prospective study.
AB  - This study investigated the role of negative emotions and metacognitions in
      predicting problem drinkers' drinking status (absence or presence of drinking)
      and level of weekly alcohol use at 3, 6 and 12 months after a course of
      treatment. A total of 70 problem drinkers with a DSM-IV diagnosis of alcohol
      abuse participated in the study. Depressive symptoms were assessed with the Beck
      Depression Inventory and symptoms of anxiety were measured with the state anxiety
      sub-scale of the State-Trait Anxiety Inventory. Metacognitions were measured with
      the Meta-Cognitions Questionnaire. Results indicated that beliefs about need to
      control thoughts predicted: (1) drinking status at 3 and 6 months; and (2) level
      of weekly alcohol use at 3, 6 and 12 months. The contribution of metacognition
      was independent of negative emotions and initial level of weekly alcohol use. The
      results support the role of metacognition in problem drinking. Given that
      metacognitions are a possible risk factor for drinking status and level of weekly
      alcohol use it is suggested that treatment for problem drinking could target this
      variable.

PMID- 19589502
TI  - A functional magnetic resonance imaging study of deliberate emotion regulation in
      resilience and posttraumatic stress disorder.
AB  - BACKGROUND: Sexual violence is an important public health problem in the United
      States, with 13% to 26% of women reporting a history of sexual assault. While
      unfortunately common, there is substantial individual variability in response to
      sexual assault. Approximately half of rape victims develop posttraumatic stress
      disorder (PTSD), while others develop no psychopathology (e.g., trauma-exposed
      non-PTSD). In this project, we examined the neural mechanisms underlying
      differences in response to sexual violence, focusing specifically on the
      deliberate modification of emotional responses to negative stimuli. METHODS:
      Using functional magnetic resonance imaging (fMRI) blood oxygenation level
      dependent (BOLD) response, we examined the neural circuitry underlying effortful
      modification of emotional responses to negative pictures in 42 women: 14 with
      PTSD after sexual trauma, 14 with no psychiatric diagnosis after sexual trauma,
      and 14 nontraumatized control subjects. RESULTS: In response to deliberate
      attempts to downregulate emotional responses, nontraumatized healthy control
      subjects were more successful than either trauma-exposed group (PTSD or non-PTSD)
      in downregulating responses to the negative pictures as measured by subjective
      rating and BOLD response in regions of prefrontal cortex (PFC). In contrast,
      after deliberate attempts to upregulate emotional responses, regions of PFC were
      activated by trauma-exposed non-PTSD subjects more than by healthy control
      subjects or PTSD subjects. CONCLUSIONS: Successful downregulation of emotional
      responses to negative stimuli appears to be impaired by trauma exposure. In
      contrast, the ability to upregulate emotional responses to negative stimuli may
      be a protective factor in the face of trauma exposure and associated with
      resilience.

PMID- 19589501
TI  - Bcl-2 polymorphism influences gray matter volume in the ventral striatum in
      healthy humans.
AB  - BACKGROUND: Bcl-2 is a major regulator of neural plasticity and cellular
      resilience. A single nucleotide polymorphism (SNP) in the Bcl-2 gene, Bcl-2
      rs956572, significantly modulates the expression of Bcl-2 protein and cellular
      vulnerability to apoptosis. We tested the hypothesis that this SNP would modulate
      gray matter (GM) volume in the limbic-cortical-striatal-pallidal-thalamic
      circuitry that plays major roles in mood regulation. METHODS: Forty-seven healthy
      subjects participated in this study (30 A carriers, 17 G homozygotes).
      Neuromorphometric differences between G homozygotes and A carriers were
      investigated using optimized voxel-based morphometry (VBM). Statistical
      significance was set at p < .05, corrected for multiple comparisons. RESULTS: A
      carriers showed less GM volume than G homozygotes in the left ventral striatum
      (p(corrected) < .05). CONCLUSIONS: Genetic variation in the Bcl-2 gene modulates
      GM volume in areas known to play key roles in the neurobiology of reward
      processes and emotion regulation and in the pathophysiology of mood disorders.
      Thus, the findings from the current study are noteworthy insofar as they converge
      with preclinical findings that Bcl-2 functions to enhance neuronal viability and
      might indirectly extend this evidence to humans.

PMID- 19589503
TI  - A brain-derived neurotrophic factor haplotype is associated with therapeutic
      response in obsessive-compulsive disorder.
AB  - BACKGROUND: Several clinical and genetic studies have focused on the role of
      brain-derived neurotrophic factor (BDNF) in the pathophysiology of various mental
      disorders. Recent lines of evidence regarding the network hypothesis of treatment
      outcome point towards the involvement of BDNF variants in the pharmacologic
      response in mood disorders (MD). Furthermore, there is strong evidence of a role
      for the serotonergic system in the pathophysiology and treatment of OCD, and
      upregulation of BDNF has been observed with various classes of antidepressants,
      including selective serotonin reuptake inhibitors (SSRI). Thus, we hypothesized
      that the BDNF gene might also be associated with treatment outcome in OCD.
      METHODS: We performed a single-marker and haplotype association study of eight
      tag single nucleotide polymorphisms in the BDNF genomic region and related this
      to pharmacologic response in a sample of 131 OCD patients. RESULTS: We found an
      association for a haplotype containing two single nucleotide polymorphisms that
      have previously been reported to be associated with treatment outcome in MD
      (rs908867 and rs1491850). CONCLUSIONS: Our results support the hypothesis that
      the BDNF gene is involved in the response to psychopharmacologic treatment even
      though these preliminary findings await replication in a follow-up sample.

PMID- 19589504
TI  - The structure of the O-specific polysaccharide from the lipopolysaccharide of
      Burkholderia anthina.
AB  - The pathogenic mechanisms of Gram-negative infection in cystic fibrosis are only
      just beginning to be explored at molecular level. Several virulence factors have
      been defined, one of the most important is the lipopolysaccharide molecule. In
      order to fully understand the mechanisms of bacterial infection and host
      recognition a full structure/activity study of lipopolysaccharide is needed. In
      the present paper, we define the complete structure of the O-specific
      polysaccharide from the lipopolysaccharide from Burkholderia anthina, an uncommon
      pathogen of cystic fibrosis patients.

PMID- 19589505
TI  - Immune modulation through RNA interference-mediated silencing of CD40 in
      dendritic cells.
AB  - RNA interference (RNAi) is an exciting mechanism for knocking down any target
      gene in transcriptional level. It is now clear that small interfering RNA
      (siRNA), a 19-21nt long dsRNA, can trigger a degradation process (RNAi) that
      specifically silences the expression of a cognate mRNA. Our findings in this
      study showed that down regulation of CD40 gene expression in dendritic cells
      (DCs) by RNAi culminated to immune modulation. Effective delivery of siRNA into
      DCs would be a reasonable method for the blocking of CD40 gene expression at the
      cell surface without any effect on other genes and cell cytotoxicity. The effects
      of siRNA against CD40 mRNA on the function and phenotype of DCs were
      investigated. The DCs were separated from the mice spleen and then cultured in
      vitro. By the means of Lipofectamine2000, siRNA was delivered to the cells and
      the efficacy of transfection was estimated by flow cytometry. By Annexine V and
      Propidium Iodide staining, we could evaluate the transfected cells viability.
      Also, the mRNA expression and protein synthesis were assessed by real-time PCR
      and flow cytometry, respectively. Knocking down the CD40 gene in the DCs caused
      an increase in IL-4 production, decrease in IL-12 production and allostimulation
      activity. All together, these effects would stimulate Th2 cytokines production
      from allogenic T-cells in vitro.

PMID- 19589506
TI  - [Deep inferior epigastric perforator flaps with an increase in the viable surface
      (turbocharging)].

PMID- 19589507
TI  - [Massive hemoperitoneum due to rupture of an spontaneous intramural oesophageal
      haematoma].

PMID- 19589508
TI  - How children block learning from ignorant speakers.
AB  - Preschool children typically do not learn words from ignorant or unreliable
      speakers. Here, we examined the mechanism by which these learning failures occur
      by modifying the comprehension test procedure that measures word learning.
      Following lexical training by a knowledgeable or ignorant speaker, 48 preschool
      aged children were asked either a standard comprehension test question (i.e.,
      "Which one is the blicket") or a question about the labeling episode (i.e.,
      "Which one did I say is the blicket"). Immediately after training, children chose
      the object labeled by an ignorant speaker when asked the episode question, but
      not when asked the semantic question. However, the advantage for episode
      questions disappeared when the same children were asked after a brief delay.
      These findings show that children encode their experiences with ignorant
      speakers, but do not form semantic representations on the basis of those
      experiences.

PMID- 19589509
TI  - Privacy preservation and information security protection for patients' portable
      electronic health records.
AB  - As patients face the possibility of copying and keeping their electronic health
      records (EHRs) through portable storage media, they will encounter new risks to
      the protection of their private information. In this study, we propose a method
      to preserve the privacy and security of patients' portable medical records in
      portable storage media to avoid any inappropriate or unintentional disclosure.
      Following HIPAA guidelines, the method is designed to protect, recover and verify
      patient's identifiers in portable EHRs. The results of this study show that our
      methods are effective in ensuring both information security and privacy
      preservation for patients through portable storage medium.

PMID- 19589510
TI  - Impaired processing of relative distances between features and of the eye region
      in acquired prosopagnosia--two sides of the same holistic coin?
AB  - Acquired prosopagnosia (AP) is characterized by impaired recognition of
      individual faces following brain damage. The nature of the functional
      impairment(s) underlying AP remains debated. Recent studies have demonstrated
      deficient processing of diagnostic information in the region of the eyes (Caldara
      et al., 2005); other studies suggest that patients fail to judge relative
      distances between facial features (Barton et al., 2002). We hypothesized that
      these apparently different observations are related to a common cause. More
      precisely, we suggest that AP arises due to an impairment of a process that
      reduces uncertainty about the nature/location of the diagnostic cues for face
      individualization: the ability to perceive multiple elements of a face as a
      single global representation (holistic processing). Being impaired at processing
      individual faces holistically, prosopagnosic patients would tend to perform
      relatively worse for processing facial areas containing multiple elements (i.e.,
      the eyes), and for elements that are widely spaced apart. Here we tested PS, a
      single case of AP, at matching unfamiliar faces differing either with respect to
      local features or inter-feature distances, over the upper and lower areas of the
      face. A pilot study and Experiment 1 confirmed that PS was extremely poor at
      using information encompassing the eyes, but was also deficient at perceiving
      relative distances between features. When uncertainty about the location and
      nature of the diagnostic cue was removed in Experiment 2, PS' performance
      remained below normal range, but she improved substantially. Most interestingly,
      her pattern of performance across the different conditions appeared qualitatively
      identical to that of normal controls. In line with previous observations of PS
      and other cases of prosopagnosia, our findings indicate that the reduced reliance
      on the area of the eyes and on relative distances between features in AP may have
      a common underlying cause-the disruption of holistic processing of the individual
      face.

PMID- 19589511
TI  - Amelioration of right spatial neglect after visuo-motor adaptation to leftward
      shifting prisms.
AB  - Visuo-motor adaptation to rightward prismatic shifts reduces signs of left
      spatial neglect on a wide range of measures(Rossetti et al., 1998; Tilikete et
      al., 2001; McIntosh et al., 2002; Pisella et al., 2002; Berberovic et al., 2004).
      As there are hemispheric asymmetries in spatial attention mechanisms, it maybe
      useful to examine whether prism adaptation can produce similar improvements in
      neglect of the right hemispace following left hemisphere damage. We report
      improvement ina patient with mild right spatial neglect following adaptation to
      leftward-shifting prisms.

PMID- 19589512
TI  - Follicular development, acquisition of mature oocytes, and pregnancy after 2
      weeks of leuprolide acetate administration during the midluteal phase.
AB  - OBJECTIVE: To present a case of aberrant follicular development, acquisition of
      mature oocytes, and pregnancy after 2 weeks of leuprolide acetate administration
      during the midluteal phase. DESIGN: Case report. SETTING: Department of
      Obstetrics and Gynecology, Aretaieio University Hospital, Athens, Greece.
      PATIENT(S): A 37-year-old white woman who was scheduled to undergo ovarian
      stimulation according to the long luteal phase protocol for IVF and ET because of
      male factor infertility. INTERVENTION(S): Twenty-first day serum P level was 5.9
      ng/dL, and a daily dose of 0.1 mg leuprolide acetate was initiated. Fifteen days
      later the patient presented for evaluation because of absence of uterine
      bleeding. Sonographic evaluation revealed the presence of five large follicles.
      Serum E(2) and P levels at this time were 1,895.0 pg/mL and 0.2 ng/mL,
      respectively. The patient received recombinant hCG (250 mg), and 36 hours later
      she underwent oocyte retrieval. Three oocytes were retrieved and fertilized by
      intracytoplasmic sperm injection. After the transfer of two embryos a singleton
      pregnancy was achieved, leading to an uneventful delivery. MAIN OUTCOME
      MEASURE(S): Serum E(2) and P and ultrasound evaluation of ovaries. RESULT(S): She
      had a singleton pregnancy, and she delivered at 39 weeks of gestation.
      CONCLUSION(S): The presence of recruitable follicles during the luteal phase of
      the cycle that responded to endogenous gonadotropins during the flare response
      before pituitary suppression could be a logical explanation of this observation.

PMID- 19589513
TI  - The antral follicle count: practical recommendations for better standardization.
AB  - OBJECTIVE: To provide recommendations for the standardized use of the Antral
      follicle count (AFC) which is used to predict ovarian response to gonadotrophin
      stimulation during assisted reproductive technology treatment. However, the
      nature of the follicles that are visualized by ultrasound and the competence of
      the oocytes held within are largely unknown. In addition, there is considerable
      variability in the clinical definitions and technical methods used to count and
      measure antral follicles in both published studies and clinical practice. DESIGN
      AND SETTING: In December 2007, specialist reproductive medicine clinicians and
      scientists attended a workshop in an effort to address these issues. Literature
      concerning the physiology and measurement of ovarian antral follicles was
      reviewed, clinical and technical considerations regarding antral follicle
      measurement were discussed, and an operational definition of AFC was developed.
      PATIENT(S): None. INTERVENTION(S): None. OUTCOME MEASURES: Simple recommendations
      were established for the standardization of AFC assessment in routine clinical
      practice. The basic clinical and technical requirements required for AFC
      evaluation were agreed upon, and a systematic method of measuring and counting
      antral follicles in routine practice was proposed. CONCLUSION(S): The use of a
      standardized approach according to the practical recommendations for antral
      follicle counting as presented is encouraged in future clinical trials and
      routine practice. The authors also advocate a systematic evaluation of these
      recommendations as standardized study data become available.

PMID- 19589514
TI  - Severity of prematurity risk in spontaneous and in vitro fertilization twins:
      does conception mode serve as a risk factor?
AB  - Because assisted reproductive technology (ART) contributes to world-wide
      increases in twin pregnancies, we retrospectively evaluated whether preterm twin
      gestations after ART are at higher risk for delivery at earlier gestational ages
      compared with naturally conceived twins. The evaluation of 204 dichorial twin
      pregnancies, 102 after natural conception and 102 after ART, matched for maternal
      age, demonstrated comparable severity of prematurity risk in both groups.

PMID- 19589515
TI  - Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome.
AB  - The purpose of this study was to compare the hormonal/clinical profiles and
      markers of bone health of women with hypothalamic amenorrhea (HA) to women with
      suspected HA and underlying polycystic ovary syndrome (PCOS). The results
      indicate that compared to women with HA, women with HA and underlying PCOS
      exhibit higher body mass index (BMI), bone mineral densities, and incidence of
      hyperandrogenism, that they may exhibit increased hyperandrogenism and irregular
      menses with weight gain, and that they remain at similar risk for osteopenia and
      osteoporosis.

PMID- 19589517
TI  - In vitro maturation for patients with repeated in vitro fertilization failure due
      to "oocyte maturation abnormalities".
AB  - OBJECTIVE: To investigate the efficacy of in vitro oocyte maturation (IVM) in
      women with repeated failure of IVF treatments due to follicular developmental
      abnormalities. DESIGN: Prospective longitudinal study. SETTING: The IVF unit of a
      university-affiliated medical center. PATIENT(S): Seven women with three or more
      IVF failures due to abnormal oocyte development resulting in no egg retrieval
      (empty follicle syndrome [EFS]), oocyte maturation arrest, or failure of
      fertilization. INTERVENTION(S): Immature oocyte collection, with or without
      minimal ovarian stimulation, IVM of the oocytes, insemination by intracytoplasmic
      sperm injection (ICSI), and embryo transfer. MAIN OUTCOME MEASURE(S): Number of
      aspirated oocytes, maturation, fertilization and cleavage rates, pregnancy, and
      ongoing pregnancy. RESULT(S): Seven women underwent seven IVM cycles. Four of
      them received a minimal stimulation of 75 IU FSH for 3-4 days. Oocytes were
      retrieved from all subjects (mean 7.1 +/- 3.3 oocytes/cycle). The in vitro
      maturation rate was 39.6% (mean 2.7 +/- 2.9 matured oocytes available for
      fertilization in four patients). The mean fertilization rate was 45.8% +/- 31.6%.
      Four women had embryo transfer. Two patients with previous genuine EFS conceived
      and delivered. CONCLUSION(S): IVM should be considered for women with previous
      genuine EFS. The role of IVM in other indications of oocyte maturation deficits
      warrants further investigation.

PMID- 19589516
TI  - Replete vitamin D stores predict reproductive success following in vitro
      fertilization.
AB  - OBJECTIVE: To determine whether 25OH-D levels in the follicular fluid (FF) of
      infertile women undergoing IVF demonstrate a relationship with IVF cycle
      parameters and outcome, hypothesizing that levels of 25OH-D in body fluids are
      reflective of vitamin repletion status. DESIGN: Prospective cohort study.
      SETTING: Academic tertiary care center. PATIENT(S): Eighty-four infertile women
      undergoing IVF. INTERVENTION(S): Follicular fluid from follicles>or=14 mm; serum
      (n = 10) and FF levels of 25OH-D. MAIN OUTCOME MEASURE(S): Clinical pregnancy
      (CP), defined as evidence of intrauterine gestation sac on ultrasound, following
      IVF; IVF cycle parameters. RESULT(S): Serum and FF levels of 25OH-D were highly
      correlated (r=0.94). In a predominantly Caucasian population (66%), significantly
      lower FF 25OH-D levels were noted in Black versus non-Black patients. Significant
      inverse correlations were seen between FF 25OH-D levels and body mass index (r=
      0.25). Significantly higher CP and implantation rates were observed across
      tertiles of FF25OH-D; patients achieving CP following IVF (n=26) exhibited
      significantly higher FF levels of 25OH-D. Multivariable logistic regression
      analysis confirmed FF 25OH-D levels as an independent predictor to success of an
      IVF cycle; adjusting for age, body mass index, ethnicity, and number of embryos
      transferred, each ng/mL increase in FF 25OH-D increased the likelihood for
      achieving CP by 6%. CONCLUSION(S): Our findings that women with higher vitamin D
      level in their serum and FF are significantly more likely to achieve CP following
      IVF-embryo transfer are novel. A potential for benefit of vitamin D
      supplementation on treatment success in infertile patients undergoing IVF is
      suggested and merits further investigation.

PMID- 19589518
TI  - The influence of type 1 diabetes mellitus on spermatogenic gene expression.
AB  - Routine semen analysis found no differences in diabetic men; however, mRNA
      profiles showed changes in the expression of genes involved in oxidative stress.

PMID- 19589519
TI  - Damaging effect of cumulus denudation on rabbit oocytes.
AB  - OBJECTIVE: To study the effect of cumulus denudation on in vitro maturation of
      rabbit oocytes. DESIGN: Experimental animal study. SETTING: Academic institution.
      ANIMAL(S): Rabbits and mice. INTERVENTION(S): Rabbit oocytes were observed
      compared with mouse oocytes. MAIN OUTCOME MEASURE(S): Developmental competence,
      membrane integrity, and apoptotic status of oocytes after cumulus denudation.
      RESULT(S): Although in vitro maturation of mouse cumulus-denuded oocytes was
      unaffected, rabbit cumulus-denuded oocytes could not mature. However, 50% of
      rabbit cumulus-intact oocytes matured normally when their gap junctions were
      sealed with 1-heptanol. Coculture with cumulus cells did not improve maturation
      of rabbit cumulus-denuded oocytes unless with an intact corona radiata. Staining
      with Hoechst 33258, Bcl-2 antibodies, and terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling showed membrane breaches or
      apoptosis of rabbit cumulus-denuded oocytes, contrary to the mouse cumulus
      denuded oocytes. Ultrastructurally, rabbit oocytes showed no perivitelline space
      but numerous long cell junctions projecting into the egg cortex, contrary to the
      mouse oocytes. However, the damaging effect of cumulus denudation was much
      relieved after preincubation of rabbit cumulus-intact oocytes with
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, and some cumulus-denuded
      oocytes prepared after preincubation matured and developed into blastocysts.
      CONCLUSION(S): [1] Cumulus denudation severely damaged rabbit oocytes leading to
      their apoptosis or degeneration, possibly because of the deep-set junctional
      complexes anchoring the oocyte and corona cells; and [2] preincubation with
      phosphodiesterase inhibitor may provide a method to avoid the damaging effect of
      cumulus denudation on rabbit oocytes.

PMID- 19589520
TI  - Laparoendoscopic single-site surgery (LESS) for ovarian cyst enucleation: report
      of first 3 cases.
AB  - OBJECTIVE: To report the feasibility of ovarian cyst enucleation by using a
      laparoendoscopic single-site trocar through a transumbilical access. DESIGN: Case
      reports. SETTING: Teaching and research hospital. PATIENT(S): Three patients
      affected by large ovarian cysts. INTERVENTION(S): Enucleation of three large
      ovarian cysts by using a laparoendoscopic single-site approach with a new
      multiport trocar and standard laparoscopic instruments. MAIN OUTCOME MEASURE(S):
      Conversion to a multiaccess standard laparoscopic technique. RESULT(S): No
      conversion to multiaccess standard laparoscopic technique and no intraoperative
      or postoperative complications were observed. Mean operative time was 79.6
      minutes. All patients were discharged home on day 1. CONCLUSION(S):
      Laparoendoscopic single-site enucleation of large ovarian cysts with ovary
      sparing is feasible with standard laparoscopic instruments, safe and effective,
      with good results in terms of cosmesis and postoperative pain. More clinical data
      are needed to confirm these advantages compared with standard laparoscopic
      technique.

PMID- 19589521
TI  - A call to provide multiple options for women in developing countries.

PMID- 19589522
TI  - Minimal stimulation using gonadotropin-releasing hormone (GnRH) antagonist and
      recombinant human follicle-stimulating hormone versus GnRH antagonist multiple
      dose protocol in low responders undergoing in vitro
      fertilization/intracytoplasmic sperm injection.
AB  - This prospective randomized study was performed to investigate the effectiveness
      of minimal stimulation using recombinant human FSH (rhFSH) and GnRH antagonist
      compared with GnRH antagonist multiple-dose protocol (MDP) in low responders
      undergoing IVF/intracytoplasmic sperm injection. Our study demonstrated that
      minimal stimulation in natural cycles provides similar pregnancy rates to the
      GnRH antagonist MDP with fewer dose and days of rhFSH used and thus can be a cost
      effective alternative as a last chance before oocyte donation in low responders.

PMID- 19589523
TI  - Adipose tissue and reproduction in women.
AB  - Adipose tissue has been viewed as the primary source of stored energy, but with
      the discovery of novel adipose tissue gene products, i.e., adipokines, another
      equally important role has emerged. Adipose tissue is a key endocrine organ
      involved in multiple processes, including glucose homeostasis, steroid
      production, immunoregulation, hematopoesis, and reproduction. The distribution of
      adipose tissue may also have a significant impact on reproductive function.

PMID- 19589524
TI  - Noninvasive metabolomic profiling as an adjunct to morphology for noninvasive
      embryo assessment in women undergoing single embryo transfer.
AB  - OBJECTIVE: To determine whether metabolomic profiling of spent embryo culture
      media correlates with reproductive potential of human embryos. DESIGN:
      Retrospective study. SETTING: Academic and a private assisted reproductive
      technology (ART) programs. PATIENT(S): Women undergoing single embryo transfer
      after IVF. INTERVENTION(S): Spent embryo culture media were collected after
      single embryo transfer on day 3 (n = 304) or day 2 (n = 181) and analyzed by near
      infrared spectroscopy. Near infrared spectral regions were correlated to
      reproductive potential using a genetic algorithm optimization. Models of these
      spectral regions were used to calculate viability indices, and were validated by
      blinded analysis of a subset (n = 60) of samples. Implantation rates were also
      compared between embryos of higher (>or=0.3) and lower (<0.3) viability indices,
      and within each morphology grade. MAIN OUTCOME MEASURE(S): Viability index and
      embryo viability. RESULT(S): Mean viability indices of embryos that resulted in
      positive fetal cardiac activity were significantly higher compared with embryos
      that did not for both day 2 and day 3 embryos. Blinded validation of the day 2
      model proved to be significant. Increasing viability index values correlated with
      an increase in pregnancy. Viability indices were found to be independent of
      morphology for both day 2 and day 3 embryos. Implantation rates were
      significantly higher among embryos with viability indices >or=0.3. CONCLUSION(S):
      Metabolomic profiling of human embryo culture media using near infrared
      spectroscopy is independent of morphology and correlates with reproductive
      potential of embryos.

PMID- 19589525
TI  - Risk factors for obstetric fistula in the Far North Province of Cameroon.
AB  - OBJECTIVE: To describe the circumstances of occurrence and identify potential
      risk factors for obstetric fistula in northern Cameroon. METHODS: A case series
      study of 42 obstetric fistula patients seeking services at the Provincial
      Hospital of Maroua, Cameroon, between May 2005 and August 2007. Structured
      interviews were conducted prior to surgical intervention. RESULTS: Among
      obstetric fistula patients, 60% had lived with obstetric fistula for more than 5
      years at the time of surgery. Eighty-one percent of patients had received no
      formal education and 86% were teenagers at their first delivery. Regarding the
      pregnancy and delivery preceding the occurrence of the fistula, 50% of women
      reported that they had received no prenatal care and 76% were in labor for more
      than 12 hours. The majority (83%) of women delivered a stillborn baby.
      CONCLUSIONS: Obstetric fistula patients in the Far North Province of Cameroon had
      a low level of education, were married at a young age, and had poor access to
      quality maternal healthcare services.

PMID- 19589526
TI  - Use of porcine small intestinal submucosa to reconstruct an ovarian defect.
AB  - OBJECTIVE: To investigate the feasibility of using porcine small intestinal
      submucosa (SIS) as a scaffold for repairing ovarian defects. METHOD: Fourteen
      female New Zealand rabbits undergoing ovarian resection were randomly allocated
      to 2 equal groups. The unilateral ovarian defects were repaired with SIS in group
      1 animals and without SIS in group 2 animals (control). The volumes of the
      ovaries were calculated and the severity of adhesions was assessed in 1 animal
      from each group each month. The ovaries were removed and examined under a
      microscope. RESULTS: The volumes of the SIS-grafted ovaries were larger than
      those of the operated ovaries of the control animals (P<0.05). The SIS-grafted
      ovaries had a lower adhesion score than the operated ovaries of the control group
      (P<0.001). SIS grafts showed hemorrhage and leukocyte infiltration until the 4th
      week after surgery, but the ovarian tissue appeared to be well organized from the
      12th to the 16th week. At the 28th week, primordial follicles were scattered in
      the SIS graft. CONCLUSION: SIS graft could be used for repairing the ovary after
      surgery.

PMID- 19589527
TI  - Peer-reviewed scientific journals in nursing: to whom are we writing?

PMID- 19589528
TI  - Efficacy criteria and cholesterol targets for LDL apheresis.
AB  - Low density lipoprotein (LDL) apheresis is now accepted as the treatment of
      choice for patients with homozygous familial hypercholesterolaemia and for
      heterozygotes with cardiovascular disease refractory to lipid-lowering drug
      therapy. However, a paucity of evidence has meant that detailed guidance on the
      extent of cholesterol reduction required to prevent the onset or progression of
      cardiovascular disease in these high risk patients is lacking. This review
      defines criteria for expressing the efficacy of apheresis, proposes target levels
      of total and LDL cholesterol for homozygotes and heterozygotes based on recent
      follow-up studies and suggests a scheme for monitoring cardiovascular disease in
      these patients. Establishing a uniform approach to data collection would
      facilitate the setting up of national or multi-national registers and might
      eventually provide the information needed to formulate evidence-based guidelines
      for LDL apheresis.

PMID- 19589529
TI  - Purification of drugs from biological fluids by counter-current chromatography.
AB  - Experiments were performed to demonstrate the potential of counter-current
      chromatography (CCC) for the isolation of drugs and their metabolites from
      biological matrices relevant to the metabolism studies of pharmaceutical
      research. Examples of typical drugs are spiked into biological media ex vivo to
      provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows
      for the detection of small molecule drugs within the matrix through selected ion
      monitoring, and fraction collection can provide material for further structural
      elucidation by NMR.

PMID- 19589530
TI  - Gas chromatography of 209 polychlorinated biphenyl congeners on an extremely
      efficient nonselective capillary column.
AB  - The gas chromatographic-mass spectrometric (GC-MS) separation of all 209
      polychlorinated biphenyl (PCB) congeners was studied on an extremely efficient 80
      m x 0.1mm i.d. capillary column coated with a 0.1 microm film of poly(5%-phenyl
      methyl)siloxane stationary phase. The quality of the separation and the number of
      resolved and coeluting peaks were compared to predictions according to the
      statistical overlap theory (SOT) and to literature data on PCB separations
      obtained by one-dimensional and comprehensive two-dimensional GC (GC x GC) and GC
      MS. Mass spectral and chemometric deconvolution procedures were used to resolve
      overlapping peaks. On the highly efficient column, 195 PCB congeners were
      resolved in 96 min separation time using spectral and chemometric deconvolution.
      This number is comparable to the best separations described in GC x GC-MS mode.
      The novel method was developed for spectral deconvolution of overlapped PCB
      congeners which was verified determining the most toxic, dioxin-like PCBs both in
      the model mixture of 209 PCBs as well as in the Aroclor 1242 and Aroclor 1254
      formulations.

PMID- 19589531
TI  - Investigation of the possibility of low pressure encapsulation of carbon dioxide
      in potassium chabazite (KCHA) and sodium chabazite (NaCHA) zeolites.
AB  - Adsorption and desorption equilibrium isotherms of CO(2) on lithium chabazite
      (LiCHA), sodium chabazite (NaCHA) and potassium chabazite (KCHA) zeolites were
      measured at 273 K up to 103 kPa using a volumetric method. The effect of cation
      type, and hence the structure of the chabazite cavities on the adsorption
      behavior was revealed through the analysis of isotherm branches. Low pressure
      hysteresis loops were observed on NaCHA and KCHA demonstrated by residuals of
      0.37 and 0.57 molecule cavity(-1) at pressures of 0.04 and 0.09 kPa,
      respectively. Hysteresis loops commenced at pressures of 0.86 kPa on NaCHA and
      1.0 5 kPa on KCHA. The earlier appearance of the hysteresis loop on KCHA over
      that on NaCHA suggested a higher extent of blockage of the 8-ring window aperture
      by K(+) cations. Low pressure hysteresis loops in molecular sieves zeolites
      reflect the intriguing possibility of encapsulation. A quadrupolar interaction
      potential was used in the formulation of an encapsulation model utilizing the
      statistical theory of the radial distribution function (rdf) and the theory of a
      perfect 3D lattice gas. The model was validated with published literature data
      using the Lennard-Jones potential. However, both models underestimated the number
      of CO(2) molecules in the cavities of the chabazite. Including the interaction
      terms of CO(2)-CO(2) and CO(2)-host cavity pairs may improve the prediction of
      the model. The cavity's dimensions and portals can be carefully designed to
      achieve greater selectivities in gas separation and stabilities in gas storage.

PMID- 19589532
TI  - Comment on "An analytic solution of capillary rise restrained by gravity" by N.
      Fries and M. Dreyer.
AB  - The porous medium model of Green and Ampt, describing flow in porous media,
      appeared earlier than the capillary model of Washburn, although both lead to
      mathematically identical models. Here, the model of Green and Ampt was related to
      the Washburn model by an examination of the parameters involved in each. Fries et
      al. [N. Fries, M. Dreyer, J. Colloid Interface Sci. 320 (2008) 259-263] presented
      an explicit solution to this model. This solution is identical to the explicit
      solution of the Green and Ampt model presented earlier by Barry et al. [D.A.
      Barry, J.-Y. Parlange, G.C. Sander, M. Sivaplan, J. Hydrol. 142 (1993) 29-46].

PMID- 19589533
TI  - Emulsification mechanism and storage instabilities of hydrocarbon-in-water sub
      micron emulsions stabilised with Tweens (20 and 80), Brij 96v and sucrose
      monoesters.
AB  - The influence of both the nature of the surfactant and surfactant concentration
      on the processes of droplet break-up and coalescence in the formation of decane
      in-water nano-emulsions in a high-pressure homogenizer was investigated.
      Emulsions were produced using a Christison Scientific M110-S microfluidiser with
      an impinging jet high-shear chamber. For all six surfactants studied (Tween 20,
      Tween 80, Brij 96v, sucrose monolaurate, sucrose monomyristate and sucrose
      monopalmate), the droplet size decreased with increasing surfactant concentration
      reaching a limiting droplet size at a surfactant concentration of 15 mM. The
      limiting droplet size for the different surfactants used were; Tween 20
      (approximately 250+/-30 nm), Tween 80 (approximately 320+/-40 nm), Brij 96v
      (approximately 200+/-20 nm) and the three sucrose monoesters had very similar
      sizes of approximately 250+/-20 nm. A hydrophobic fluorescent dye (1
      undecylpyrene) was used to establish the extent of competition between droplet
      break-up and coalescence in the emulsification process. For all the emulsifiers
      studied, droplet coalescence in the process reduced as the amount of emulsifier
      increased, becoming zero at concentrations of about 15 mM, i.e. the same
      concentration as that required to produce the limiting minimum droplet size. This
      shows that in the emulsification process droplet size is determined by both break
      up and re-coalescence events, and at lower surfactant concentrations (<15 mM)
      that the final droplet size is probably a consequence of multiple break-up
      events. Emulsion stability over 200 h was investigated by measuring changes in
      the droplet size using dynamic light scattering. The increase in droplet volume
      was shown to be linear with respect to time, indicating an Ostwald ripening
      process. The observed ripening rate for the three sucrose monoesters
      (monopalmitate, monomyristate and monolaurate) was approximately 20 nm(3) s(-1),
      which is the ripening rate calculated using the Lifshitz-Slesov-Wagner (LSW)
      theory. This ripening rate is the change in radius that results from movement of
      the oil through the continuous phase, taking into account the oil solubility in
      water and the diffusion coefficient of the decane-in-water. The ripening rate for
      Brij 96v was about three times larger than the calculated rate and there is an
      indication that the ripening rate increases slightly with increasing surfactant
      concentration, indicating that some enhancement due to the presence of micelles
      has occurred. With Tween 80 and 20 the ripening rates were 20 and 40 times,
      respectively, larger than those calculated using the solubility and diffusion
      coefficients. The increased rate has been shown to be first order with respect to
      the surfactant concentration indicating micelle mediated ripening. It is
      hypothesized that an optimum formulation for the sub-micron emulsion with these
      types of surfactant, will balance surfactant concentration to minimize droplet
      size during processing while aiming to minimize or prevent Ostwald ripening.

PMID- 19589534
TI  - Electrostatic and electrokinetic effects on hindered convection in pores.
AB  - The sieving of macromolecules in ultrafiltration is affected by solute and pore
      charge, as well as size. A large, relatively rigid molecule such as a globular
      protein may be viewed as a particle in an electrolyte solution. Charge may
      influence both its equilibrium partition coefficient and its lag coefficient (G),
      which is the ratio of particle to fluid velocity. Partitioning had been examined
      previously for spheres in cylindrical pores by using continuum double layer
      theory to evaluate the electrostatic potential energy (E). The present objective
      was to estimate G for particles and pores of like charge. Particle or fluid
      motion tends to distort the diffuse double layers, an effect termed "relaxation,"
      which increases the drag on the particle. The streaming potential that arises
      from flow through a charged pore under open-circuit conditions also increases the
      drag on a confined, stationary particle. These electrokinetic effects were
      quantified using finite element solutions of the equations of motion, Poisson's
      equation, and conservation equations for small ions in the electrolyte. It was
      found that charge effects generally reduce G, with relaxation tending to be the
      more important contributor. Thus, a freely suspended, charged particle will move
      through a pore more slowly than an uncharged one of the same size. However, the
      effects of E on sieving outweigh those of the electrokinetic decrease in G. That
      is, charge influences sieving mainly by altering the partition coefficient.

PMID- 19589535
TI  - Selenium adsorption to aluminum-based water treatment residuals.
AB  - Aluminum-based water treatment residuals (WTR) can adsorb water- and soil-borne
      P, As(V), As(III), and perchlorate, and may be able to adsorb excess
      environmental selenium. WTR, clay minerals, and amorphous aluminum hydroxide were
      shaken for 24 h in selenate or selenite solutions at pH values of 5-9, and then
      analyzed for selenium content. Selenate and selenite adsorption edges were
      unaffected across the pH range studied. Selenate adsorbed on to WTR, reference
      mineral phases, and amorphous aluminum hydroxide occurred as outer sphere
      complexes (relatively loosely bound), while selenite adsorption was identified as
      inner-sphere complexation (relatively tightly bound). Selenite sorption to WTR in
      an anoxic environment reduced Se(IV) to Se(0), and oxidation of Se(0) or Se(IV)
      appeared irreversible once sorbed to WTR. Al-based WTR could play a favorable
      role in sequestering excess Se in affected water sources.

PMID- 19589536
TI  - Electrokinetic potentials of Al2O3 in concentrated solutions of metal sulfates.
AB  - The zeta potentials of alumina (10% by mass dispersions) in 0.1-1 M solutions of
      metal sulfates were determined by means of the electroacoustic method. The
      background correction was used to account for the electroacoustic signal of the
      electrolyte. The zeta potentials in the solutions of alkali sulfates were in the
      range from -8 to -19 mV. They were rather insensitive to the pH (4-9.5), and to
      the nature and concentration of the salt. In MgSO(4) solutions (0.05-0.5 M, pH 4
      8), the zeta potentials were also negative (-3 to -9 mV) showing the preference
      of alumina to adsorb sulfate anions rather than magnesium cations.

PMID- 19589537
TI  - Cationic-anionic vesicle templating from fluorocarbon/fluorocarbon and
      hydrocarbon/fluorocarbon surfactants.
AB  - Spontaneous catanionic vesicle formation is studied in systems comprising
      fluorinated surfactants, the cationic/anionic fluorinated surfactant system of
      1,1,2,2-tetrahydroperfluorododecylpyridinium chloride (HFDPC)/sodium
      perfluorooctanoate (SPFO) and the analogous mixed hydrocarbon/fluorocarbon
      surfactant system of cetylpyridinium bromide (CPB)/SPFO. Aggregate formation is
      explored in the anionic-rich surfactant system (weight fraction of anionic
      surfactant, gamma=0.66-0.85) and a total surfactant concentration range of 0.1-2%
      wt/wt for the fluorinated system and 0.4-2.2% wt/wt for the mixed
      hydrocarbon/fluorocarbon system. Vesicle sizes range from approximately 40 to 200
      nm for CPB/SPFO, as determined by negative staining transmission electron
      microscopy (TEM) and confirmed by dynamic light scattering. The primary vesicle
      diameter observed by TEM in the catanionic fluorinated/fluorinated surfactant
      system is smaller (20-50 nm). However, the relatively few larger vesicles (100
      nm) in the HFDPC/SPFO system dominate the dynamic light scattering measurements.
      Successful templating of silica hollow spheres is demonstrated in both HFDPC/SPFO
      and CPB/SPFO vesicle systems, using tetramethoxysilane (TMOS) as the silica
      precursor for the acid-catalyzed synthesis. The size of the resulting hollow
      silica particles is consistent with the templating of vesicles of the size range
      observed by TEM. Changes in zeta potential are used to monitor colloidal
      stability. At the conditions investigated (TMOS/surfactant weight ratios of 0.25
      1.0, pH 3), the colloidal silica particles templated from fluorinated HFDPC/SPFO
      vesicles are more stable than the particles templated from the corresponding
      mixed fluorinated CPB/SPFO system. Further improvement of the stability of the
      colloidal particles is achieved in the CPB/SPFO systems by titrating the acid
      synthesis solution with base over the course of the particle synthesis.

PMID- 19589538
TI  - Therapeutic effect of Y-27632 on chronic allograft nephropathy in rats.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is a major cause of late
      allograft loss. Recent evidences suggest that Rho and its downstream effector
      ROCK may be greatly involved in the progression of renal fibrosis. Inhibition of
      Rho/ROCK pathway might interact with the inflammatory process in the renal
      interstitium, and antagonize the process of epithelial-to-mesenchymal transition
      (EMT). We hypothesized that Y-27632 could inhibit the chronic inflammatory
      process and prevent the progression of CAN. MATERIALS AND METHODS: Fisher (F344)
      kidneys were orthotopically transplanted into Lewis rat recipients. Lewis to
      Lewis rat kidney transplantation was served as the syngeneic control (Syn group).
      Allograft recipients were randomized and treated with either cyclosporine A alone
      (Allo group), or in combination with Y-27632 (30 mg/kg body weight/d
      intragastric, Y-27632 group). Renal function and urine protein excretion levels
      of the rats were analyzed. Animals were sacrificed 12 wk post-transplantation for
      histological and immunohistochemical studies, as well as analysis of the
      expression levels of chemokines, transforming growth factor (TGF-beta) 1 and
      alpha smooth muscle actin (alpha-SMA). RESULTS: Renal function deteriorated
      progressively in the Allo group, and there was typical CAN morphology in the
      kidneys. However, Y-27632-treatment significantly prevented the deterioration of
      graft function, lessened the level of urine protein excretion, and preserved the
      renal structure. Attenuation of ED1 positive mononuclear cell infiltration and
      amelioration of tubulointerstitial fibrosis were achieved by Y-27632
      intervention. This was associated with down-regulation of the expression of
      tubular monocyte chemoattractant protein-1, RANTES (regulated upon expression
      normal T cell expressed and secreted), and phosphorylated NF-kappaB (which was a
      marker for activation). Profibrotic protein (TGF-beta1) and alpha-SMA, a marker
      of EMT, were significantly down-regulated by Y-27632 treatment as well.
      CONCLUSIONS: The Rho/ROCK pathway plays an important role in the progression of
      CAN, and specific inhibition of Rho activity by Y-27632 showed favorable effects
      on blocking renal interstitial inflammation and fibrosis, thus efficiently
      retarding the development of CAN, which might provide us with a novel strategy to
      improve long-term renal graft survival.

PMID- 19589540
TI  - ATIII attenuates endotoxemia induced healing impairment in the colon.
AB  - BACKGROUND: Intra-abdominal infections are considered a contributing factor to
      the impairment of anastomotic healing in patients undergoing surgical procedures
      of digestive system. Antithrombin (ATIII) is known to improve the
      microcirculation in sepsis. We hypothesized that it may also positively influence
      the healing of the colon anastomoses under endotoxemia. MATERIALS AND METHODS:
      Ninety Balb/c mice (n = 10 per group on day 2, 4, and 7) were randomly assigned
      to three groups: Control (N), Sepsis (S) (administration of lipopolysaccharides
      (LPS) dosed at 2 mg/kg bodyweight, 18 h before colon surgery), and Sepsis with
      ATIII therapy (SIII) (administration of LPS and ATIII). All the animals underwent
      colonic anastomoses. Immediately after their completion, microcirculatory
      parameters were measured, and both macroscopic and histological parameters were
      assessed on day 2, 4, and 7 postoperation. Additionally, immunohistology studies
      were performed for CD31, ssDNA, and iNOS, along with an examination for bacterial
      translocation to the mesenteric lymph nodes. RESULTS: Compared with group S, the
      functional capillary network was denser in the control group N (P < 0.001) and
      group SIII (P < 0.01). Mean bursting pressures were significantly lower in group
      S compared with group N, on day 2, 4, and 7, and with group SIII on day 2 and 7.
      At the anastomosis, the inflammatory infiltrate in group S was denser compared
      with groups N (P < 0.001) and SIII (P < 0.01). Furthermore, the apoptotic rate
      was higher, and the vascular density was lower on day 7 in group S compared with
      groups SIII and N (P < 0.05). Bacterial translocation decreased over time (P <
      0.05) with no significant differences between the groups. CONCLUSION: ATIII
      improved the anastomotic microcirculatory parameters and anastomotic healing in
      mice with endotoxemia, though the improvement failed to achieve the levels of the
      control mice.

PMID- 19589541
TI  - Cell suspensions of autologous keratinocytes or autologous fibroblasts accelerate
      the healing of full thickness skin wounds in a diabetic porcine wound healing
      model.
AB  - Autologous dermal fibroblasts may be useful in the treatment of diabetic skin
      wounds. We hypothesized that cultured fibroblasts or cultured keratinocytes would
      not only survive in a hyperglycemic wound environment but also enhance the rate
      of re-epithelialization. We previously developed a new porcine model of delayed
      cutaneous wound healing in the diabetic pig. Full thickness wounds were created
      on the dorsum and dressed with polyurethane chambers to keep the wounds wet and
      to allow for wound fluid monitoring. Suspensions of either autologous fibroblasts
      or autologous keratinocytes were injected into full thickness wounds and compared
      with wounds treated in a wet environment in normal saline. Serum glucose and
      wound fluid glucose concentrations were monitored daily. Wound contraction was
      monitored and biopsies taken on day 12. Transplantation of suspensions of
      autologous fibroblasts or autologous keratinocytes enhanced re-epithelialization
      of cutaneous full thickness wounds. Wounds treated with autologous fibroblasts
      showed a re-epithelialization rate of 86.75% and wounds treated with autologous
      keratinocytes showed a re-epithelialization rate of 91.3%. This is compared with
      a re-epithelialization rate of 56.8% seen in the normal saline treated wounds.
      While previous studies have shown fibroblasts suspension to have little effect in
      the treatment of full thickness wounds in nondiabetic wounds, this study shows a
      clear beneficial effect in the use of fibroblast or keratinocyte suspensions for
      the cutaneous healing of diabetic wounds in pigs.

PMID- 19589539
TI  - Perioperative iloprost and endothelial progenitor cells in uremic patients with
      severe limb ischemia undergoing peripheral revascularization.
AB  - The incidence of severe limb ischemia (SLI) is high among haemodialysis (HD)
      patients. Limb rescue rate after surgical revascularization is relatively poor
      compared with patients with normal renal function. Prostanoids are an interesting
      category as adjuvants to revascularization. New vessel growth develops not
      exclusively by proliferation of endothelial cells in vascular extremities but
      also by cells mobilized from the bone marrow (HSC), transformed into endothelial
      progenitor cells (EPC) contributing to both re-endothelialization and
      neovascularization. Basal number of HSC and EPC is significantly reduced in HD
      patients and correlated with a subsequent defective neovascularization. The aim
      of this study was to evaluate the effects of perioperative treatment with
      iloprost in uremic patients with acute ischemia of lower limbs, undergoing
      surgical revascularization, on endothelial progenitor cells, hypothesizing a
      possible biological mechanism induced by the prostanoids. A search was also made
      for vascular remodeling processes through the analysis of the concentrations of
      soluble adhesion molecules (i-CAM, v-CAM, e-selectin), biochemical markers of
      endothelial activation. Thirty HD patients with SLI undergoing peripheral
      revascularization were enrolled (15 were treated with iloprost and 15 with a
      placebo). Iloprost was administered as an intra-arterial bolus of 3000 ng over 1
      to 3 min immediately after revascularization and in the same affected artery.
      Serum samples were taken before revascularization (T0), at 6 (T6) and 24 h (T24)
      after infusion to measure sICAM-1, sE-selectin, and sVCAM-1, and for
      quantification of HSC and EPC. Progenitors were identified by specific surface
      markers CD34+, CD133+ and VEGFR2+. Count was conducted using PROCOUNT performed
      in a TRUCOUNT tube and with a FACSort flow cytometer. Before revascularization,
      all patients showed a decreased number of HSC and EPC. After 6 h, HSC augmented
      significantly compared with T0 in both groups. The iloprost group attained a
      significant increase compared with the placebo group. HSC levels reduced
      drastically at T24. EPC augmented significantly compared with basal level after
      24 h. In the iloprost group, the increase was considerable compared with the
      placebo group. A close negative correlation, assessed by Pearson coefficient (r),
      was found between HSC and EPC at T24 in the iloprost group (R = 0.82 P < 0.01).
      Adhesion molecules had increased levels at T6 and T24 in both groups. Moreover, a
      close positive correlation, assessed by Pearson coefficient, was found between
      EPC and adhesion molecules in both groups but the iloprost group maintained a
      better statistical association. Revascularization stimulated HSC and EPC release
      from bone marrow but at a different time: HSC increased suddenly at 6 h and
      diminished to a minimal amount at T24, conversely, EPC increased significantly
      only at T24. Iloprost treatment was able to amplify this mechanism validating
      recent findings (North TE et al., [31]). Adhesion molecules as markers of
      endothelial activation and vascular development confirmed this tendency.

PMID- 19589542
TI  - Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and
      sepsis.
AB  - BACKGROUND: Immune function after hemorrhagic shock and subsequent sepsis is
      characterized by an early proinflammatory burst of IL-6, and high IL-6 levels
      have been linked to high mortality after trauma and in sepsis. Trans-signaling is
      defined as the activation of cells that do not express the membrane bound IL-6
      receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc
      is able to bind the IL-6/sIL-6R complex, and beneficial effects of IL-6 blockade
      in chronic inflammatory diseases have been shown. The first aim of this study was
      to investigate the potential effect of a gp130 blockade via the gp130-Fc antibody
      causing impairment of IL-6 signaling. The second aim was to find out what role
      the IL-6/sIL-6R complex can play in the context of hemorrhagic shock and
      subsequent sepsis as an acute inflammatory disease. MATERIAL AND METHODS: Male
      CBA/J mice were subjected to hemorrhagic shock (35+/-5 mmHg for 90min and fluid
      resuscitation) or sham operation. At resuscitation each animal received either
      0.5mg gp130-Fc or placebo (PL) i.p. At 48 h after resuscitation, both splenocytes
      and peritoneal macrophages (pMphi) were harvested or polymicrobial sepsis was
      induced by cecal ligation and puncture. Survival over 10 d was determined.
      Release of IL-6, TNF-alpha, and IL-10 of pMphi and release of IL-2, IL-10, and
      IFN-gamma of splenocytes was assessed by ELISA. Proliferation of splenocytes and
      their morphologic damage were determined. RESULTS: Binding of the IL-6/sIL-6R
      complex by gp130-Fc led to significant lower IL-6 levels compared with placebo
      treated animals. Placebo treated males showed depressed proinflammatory immune
      response (IL-2, IL-6) after hemorrhagic shock. While splenocyte proliferation was
      significantly reduced directly after hemorrhagic shock and restored after 48 h by
      gp130-Fc, pMphi cytokine release was not influenced. Finally, survival appeared
      to be unaffected. CONCLUSION: Transsignaling does not seem to play a pivotal role
      in the development of the immune dysfunction and mortality in our model of
      hemorrhage and subsequent sepsis.

PMID- 19589543
TI  - Noninvasive tissue oxygen saturation measurements identify supply dependency.
AB  - BACKGROUND: Hemorrhagic shock can lead to multiple organ failure and death. We
      have previously shown that noninvasive measurement of tissue oxygen saturation
      (StO(2)) has predictive value for outcomes in patients suffering hemorrhagic
      shock. Our study objectives were twofold: (1) to compare invasive and noninvasive
      measurements of local and systemic tissue hemoglobin oxygenation and (2) to
      compare the effects of various physiologic conditions seen in patients in
      hemorrhagic shock on tissue hemoglobin oxygenation. MATERIALS AND METHODS: We
      studied pigs in controlled conditions mimicking shock induced by one of the
      following: hypothermia, isovolemic hemodilution, or manipulations of vascular
      tone. We obtained both invasive and noninvasive measurements in a hind limb of
      StO(2), tissue hemoglobin index, femoral artery and venous flows, blood
      pressures, temperature, pH, pO(2), pCO(2), oxygen saturation, lactate,
      hemoglobin, and base excess. In all cases, we measured baseline values in both
      experimental and control hind limbs. RESULTS: We found that tissue hemoglobin
      oxygenation did not vary significantly over relevant physiologic temperatures.
      Under all physiologic conditions tested, we found supply-dependent oxygen
      consumption at oxygen levels less than 7 mL O(2)/min/kg. Similarly, we found that
      local oxygen delivery in animals subjected to varying degrees of isovolemic
      hemodilution or altered vascular tone was correlated with supply-dependent oxygen
      consumption, as measured by local noninvasive StO(2). CONCLUSIONS: Noninvasive
      StO(2) measurements are valid and durable over a wide range of physiologic
      conditions and correlate with invasively-measured oxygen delivery.

PMID- 19589544
TI  - Lentivirus-based DsRed-2-transfected pancreatic cancer cells for deep in vivo
      imaging of metastatic disease.
AB  - Pancreatic cancer is one of the most aggressive human malignancies. One of the
      leading causes of pancreatic cancer death is metastasis. In this report, we
      developed in vitro, a stable high-expression red fluorescent protein (RFP)
      transductant of the pancreatic cancer cells with a lentiviral expression vector
      containing the DsRed-2 RFP gene. These fluorescent pancreatic cancer cells were
      used to establish an orthotopic metastatic model and an experimental angiogenesis
      metastatic model of pancreatic cancer in nude mice. The high-level expression of
      RFP enables the imaging of distant micrometastases in their target organs. RFP
      expression did not interfere with the biological properties of the transformed
      cells compared to the parental cell line. We also demonstrated that lentiviral
      transduced pancreatic cancer cells maintained stable high-level RFP expression
      during their growth in vitro and in vivo. The fluorescence was sufficient to
      noninvasively image tumor growth and metastasis, even in deep tissue such as the
      lung. The results indicate the benefit of lentivirus transfection of cancer cells
      for high expression of RFP and for sensitive in vivo imaging of metastatic
      pancreatic cancer.

PMID- 19589545
TI  - Montelukast protects axial pattern rat skin flaps against ischemia/reperfusion
      injury.
AB  - BACKGROUND: Recent studies have shown that neutrophils play an important role in
      the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin
      flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether
      the administration of montelukast sodium, a selective reversible cysteinyl
      leukotriene 1 (CysLT1) receptor antagonist, decreases neutrophil infiltration and
      promotes flap survival. METHODS: Eighteen rats were used and randomly divided
      into three groups (n=6 for each group). Group I was the sham group and did not
      undergo ischemic insult; rather, normal saline (1 mL) was administrated
      intraperitonealy (i.p.) 30 min before surgery and continued for 6 d. Group II
      (control) and Group III (montelukast) underwent 12 h of ischemic insult. For
      Group II, normal saline (1 mL) was injected i.p. 30 min before the surgery and
      immediately before reperfusion, and this continued for 6 d. In Group III, 1 mL of
      montelukast (10mg/kg) was injected i.p. and continued for 6 d. Malondialdehyde
      (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) enzyme activities
      were investigated. Histological evaluation was made to investigate the tissue
      neutrophil count. Survival areas were assessed at 7 d postoperatively. RESULTS:
      Group III (montelukast- treated) showed a significantly higher survival rate than
      Group II (control) (P=0.029) but a lower survival rate than Group I (sham).
      Histological and biochemical assays corroborated this data. CONCLUSION: This
      study suggests that montelukast CysLT1 receptor antagonist montelukast reversed
      I/R-induced oxidant responses and improved flap survival by inhibiting neutrophil
      infiltration and balancing oxidant and antioxidant status.

PMID- 19589546
TI  - Knockdown of interleukin-2 by shRNA-mediated RNA interference prolongs liver
      allograft survival.
AB  - Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and
      homeostasis. The failure of IL-2 biosynthesis may play a critical role in
      tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA
      (shRNA) on regulating acute rejection in rat liver transplantation. To this end,
      we successfully designed and selected an effective interference plasmid, pIL-2B.
      The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the
      no transfection group. Lewis to BN orthotopic liver transplant model was used to
      explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with
      pIL-2-shRNA survived longer (median survival time of 16 d range 7-21 d) than
      those with empty vector (11; range 5-13) or saline (9; range 5-13) (P<0.05), and
      was inferior to those with CsA (24; range 13-36, P<0.05). The IL-2-shRNA
      attenuated acute rejection with decreased apoptosis of hepatocytes and reduced
      cytokine production of IL-2, tumor necrosis factor-alpha (TNF-alpha), and
      interferon-gamma (IFN-gamma) in the graft. Our results suggest that IL-2
      targeting using RNA interference approach may be of potential interest in organ
      transplantation.

PMID- 19589547
TI  - Bovine thrombin safety reporting: an example of study design and publication
      bias.
AB  - BACKGROUND: Bovine thrombin, a popular hemostat and sealant since 1945, has
      recently been subjected to clinical trial testing due to reformulations in 1998.
      We sought to compare adverse event rates of early observational studies with
      those of later interventional trials. METHODS: A MEDLINE-based literature search
      in publications that report safety in bovine thrombin exposed surgical patients
      was extracted and reviewed. RESULTS: In 38 studies, about half were case reports
      and 31.5% were interventional trials. In case reports, 41% of authors reported
      severe coagulopathic adverse events. In contrast, whereas blood complications
      were common in large trials, no association of harm was established for bovine
      thrombin product exposure and/or immunization. CONCLUSIONS: In this review, later
      clinical trials failed to reproduce the common and severe coagulopathy predicted
      by earlier observational studies in bovine exposed patients. This example
      illustrates that perceptions of safety can change as a function of study design,
      even for a widely adopted, well established biologic such as thrombin. Caution
      must be exercised in interpreting evidence from observational studies alone.

PMID- 19589548
TI  - [Utility of urokinase in percutaneous drainage treatment of intra-abdominal
      abscesses].
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to analyze the usefulness of
      the treatment with Urokinase (UK) in percutaneous drainage of intra-abdominal
      abscesses (IAA). PATIENTS AND METHODS: Prospective, observational study of 50
      patients treated in the Interventional Radiology Unit from University Hospital
      Lozano Blesa .Zaragoza. Spain. All procedures were performed under local
      anesthesia and ultrasound control, using Pigtail catheters (12-14 F). PH , D
      dimer determination and microbiological studies were done from the initial
      aspirated sample. Subsequently, we injected 10 cc of UK (100,000 IU) 3 times a
      day for 3 days at least. Variables study: RESOLUTION (Principal variable). Other
      variables included epidemiological, specific prognostic indexes (Mannheim,
      Altona); types of abscesses (location/origin), pH, D-Dimer and microbiology.
      Technical success, days of treatment, stay and mortality were also analyzed.
      RESULTS:  RESOLUTION: 86%; technical success: 100%; subsequent surgery: 3 cases.
      Mean treatment days: 7. Mean stay: 12 days. Death rate: 8% (PMI=or>13 and PIA
      II=or<-3,76). CONCLUSIONS: The treatment of IAA through percutaneous drainage and
      washed with urokinase, is a safe, feasible and reproducible technique. The
      outcomes are similar to those reported previously.

PMID- 19589550
TI  - Seroprevalence of and risk factors for Toxoplasma gondii in sheep raised in the
      Jaboticabal microregion, Sao Paulo State, Brazil.
AB  - Seroprevalence of and risk factors for toxoplasmosis in sheep from different
      properties in the Jaboticabal microregion, Sao Paulo State, Brazil were
      determined. Antibodies to Toxoplasma gondii were found in sera of 52.0% of 488
      sheep tested by indirect fluorescent antibody test (IFAT > or =64). T. gondii
      seropositivity in sheep was significantly associated with gender of the sheep,
      pasturing system, contact with cats, and the use of mineral supplements and the
      type of feed.

PMID- 19589549
TI  - The gammadelta cells as marker of non-seroconverted cattle naturally infected
      with Mycobacterium avium subspecies paratuberculosis.
AB  - Early diagnosis of MAP infection is a pressing need to enable efficient
      intervention with the spread of MAP infection in herds. Hence, study of
      lymphocyte subsets and their expressed adhesion molecules could contribute in
      defining a distinct diagnostic marker (or markers) at the subclinical period of
      the infection that could in turn facilitate the development of effective
      diagnostic approach. In accordance with this objective, milk and blood samples
      were collected from two groups of cattle naturally infected with MAP and their
      corresponding negative controls. Group (C) comprised 3-4 year-old ELISA
      negative/PCR positive-cattle that were considered as subclinical seronegative low
      shedder group (early stage). Group (A) included 6-8 year-old ELISA positive
      cattle, which were considered as a clinical seropositive group (late stage). Flow
      cytometry of B cells, CD8(+), CD4(+) and gammadelta cells and the adhesion
      molecules CD44(+), CD62L, LFA-1 and LPAM-1 indicated increase in CD4(+) and B
      cells levels, with higher levels in blood than milk of group A, and significant
      expression of CD44(+) in blood and milk and LPAM-1 in blood only. The CD8(+)
      cells count in milk was higher than blood in the late stage. The peculiar feature
      of the early stage (group C) was the high level of gammadelta cells in the blood
      and milk, with tendency to express high level of CD62L. Compelling evidence could
      support the assumption that the dominant gammadelta cells at early stage of MAP
      infection could be of CD8CD2(-)WC+1(+) phenotype. gammadelta cells appear as
      promising markers in defining early changes of MAP infection due to their
      important role in priming innate and cell mediated immunity. Possible utilization
      of these peculiar changes in the gammadelta cells level in the early diagnosis of
      MAP infection should be the subject of further research.

PMID- 19589551
TI  - [Atypical progressive multifocal leukoencephalopathy (PML) in a patient with
      pulmonary sarcoidosis].
AB  - INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a demyelinating
      disease of central nervous system due to the JC virus. PML generally occurs in
      immunocompromised hosts and has a fatal outcome. OBSERVATION: We report a case of
      an atypical PML in a patient with pulmonary sarcoidosis: MRI showed multifocal
      and punctate contrast enhancements. The diagnostic was made by brain biopsy.
      CONCLUSION: The pathophysiology of this association is probably related to the
      immunodepression induced by sarcoidosis.

PMID- 19589555
TI  - Evaluation of two spike-and-recovery controls for assessment of extraction
      efficiency in microbial source tracking studies.
AB  - Quantitative PCR (qPCR), applied to complex environmental samples such as water,
      wastewater, and feces, is susceptible to methodological and sample related
      biases. In this study, we evaluated two exogenous DNA spike-and-recovery controls
      as proxies for recovery efficiency of Bacteroidales 16S rDNA gene sequences
      (AllBac and qHF183) that are used for microbial source tracking (MST) in river
      water. Two controls--(1) the plant pathogen Pantoea stewartii, carrying the
      chromosomal target gene cpsD, and (2) Escherichia coli, carrying the plasmid
      borne target gene DsRed2--were added to raw water samples immediately prior to
      concentration and DNA extraction for qPCR. When applied to samples processed in
      replicate, recovery of each control was positively correlated with the observed
      concentration of each MST marker. Adjustment of MST marker concentrations
      according to recovery efficiency reduced variability in replicate analyses when
      consistent processing and extraction methodologies were applied. Although the
      effects of this procedure on accuracy could not be tested due to uncertainties in
      control DNA concentrations, the observed reduction in variability should improve
      the strength of statistical comparisons. These findings suggest that either of
      the tested spike-and-recovery controls can be useful to measure efficiency of
      extraction and recovery in routine laboratory processing.

PMID- 19589554
TI  - Fate of pharmaceuticals in contaminated urban wastewater effluent under
      ultrasonic irradiation.
AB  - The application of sonolysis (US) for remediation of wastewater is an area of
      increasing interest. The aim of this study was to evaluate the ultrasonic (US)
      process on the degradation of pharmaceuticals (diclofenac (DCF), amoxicillin
      (AMX), carbamazepine (CBZ)) in single solutions and also in three mixtures spiked
      in urban wastewater effluent. Several operating conditions, such as power density
      (25-100 W L(-1)), initial substrate concentrations (2.5-10 mg L(-1)), initial
      solution pH (3-11), and air sparging were varied for the evaluation and
      understanding of the process. The degradation (as assessed by measuring UV
      absorbance), the generation of hydroxyl radicals (as assessed measuring H(2)O(2)
      concentration), the mineralization (in terms of TOC and COD removal), and the
      aerobic biodegradability (as assessed by the BOD(5)/COD ratio) were monitored
      during sonication. Ecotoxicity to Daphnia magna, Pseudokirchneriella subcapitata
      and Lepidium sativum before and after treatment was also evaluated. It was found
      that the pharmaceuticals conversion is enhanced at increased applied power
      densities, acidic conditions and in the presence of dissolved air. The reaction
      rate increases with increasing initial concentration of single pharmaceuticals
      but it remains constant in the mixtures, indicating different kinetic regimes
      (i.e. first and zero order respectively). Mineralization is a slow process as
      reaction by-products are more stable than pharmaceuticals to total oxidation;
      nonetheless, they are also more readily biodegradable. The toxicity of the
      wastewater samples before and after contamination with pharmaceuticals both in
      mixtures and in single substance-containing solutions was observed more severely
      on P. subcapitata; a fact that raises concerns in regards to the discharge of
      such effluents. D. magna displayed less sensitivity compared to P. subcapitata
      because it belongs in a lower taxonomic species than D. magna. The germination
      index of L. sativum in the presence of the drugs' mixture was stimulated instead
      of inducing any toxicity effect and this might be attributed to the fact the
      sample, laden with very low drug concentrations was able to act as a provider of
      additional nutrient elements.

PMID- 19589556
TI  - Potential genotoxic effects of melted snow from an urban area revealed by the
      Allium cepa test.
AB  - The presence of well-known atmospheric pollutants is regularly screened for in
      large towns but knowledge about the effects of mixtures of different pollutants
      and especially their genotoxic potential is largely missing. Since falling snow
      collects pollutants from the air, melted snow samples could be suitable for
      evaluating potential genotoxicity. For this purpose the Allium cepa anaphase
      telophase test was used to analyse melted snow samples from Belgrade, the capital
      city of Serbia. Samples of snow were taken at two sites, characterized by
      differences in pollution intensity, in three successive years. At the more
      polluted site the analyses showed a very high degree of both toxicity and
      genotoxicity in the first year of the study corresponding to the effects of the
      known mutagen used as the positive control. At the other site the situation was
      much better but not without warning signals. The results showed that standard
      analyses for the presence of certain contaminants in the air do not give an
      accurate picture of the possible consequences of urban air pollution because the
      genotoxic potential remains hidden. The A. cepa test has been demonstrated to be
      very convenient for evaluation of air pollution through analyses of melted snow
      samples.

PMID- 19589557
TI  - Equilibrium sampling through membranes (ESTM) of acidic organic pollutants using
      hollow fibre modules in continuous steady-state mode.
AB  - Hollow fibre (HF) membrane modules were applied in continuous mode for
      equilibrium sampling through membranes (ESTM) of polar organic pollutants.
      Phenolic compounds (chlorophenols, cresols and phenol) served as model substances
      and ESTM was tuned towards the measurement of freely dissolved concentrations
      (C(free)). HF membrane modules were constructed using thin-walled membrane, 1-m
      module length and low packing density in order to optimise the uptake kinetics of
      the analytes into the acceptor solution. Such custom made devices were tested and
      compared to commercially available modules. The former modules performed best for
      continuous ESTM. The custom made modules provided steady-state equilibrium within
      20-40 min and enrichment that was in general agreement with calculated
      distribution ratios between acceptor and sample. In experiments during which
      sample concentration was changed, acceptor response time to decreased sample
      concentration was around 30 min for custom built modules. In the presence of
      commercial humic acids, analytes showed lower steady-state enrichment, which is
      due to a decrease in C(free). Continuous ESTM may be automated and is suggested
      for use in online determination of C(free) of pollutants and studies on sorption
      of pollutants. Future studies should include optimisation of the membrane liquid
      and factors regarding the residence time of the acceptor solution in the fibre
      lumen. Qualitative aspects of DOM should also be included, as natural DOM can be
      fractionated. C(free) could be correlated to DOM properties that have previously
      been shown to influence sorption, such as aromaticity, carboxylic acid content
      and molecular size.

PMID- 19589558
TI  - Radiocarbon and stable isotope investigations at the Central Rhineland sites of
      Gonnersdorf and Andernach-Martinsberg, Germany.
AB  - The late glacial open-air sites of Gonnersdorf and Andernach-Martinsberg in the
      German Central Rhineland are well known for their Magdalenian occupation and
      activities. The latter site also produced evidence for a younger, Final
      Palaeolithic occupation of the locality by people of the Federmessergruppen. Both
      sites are particularly well preserved, largely due to their burial beneath
      volcanic deposits of the late glacial Laacher See eruption. We conducted a
      program of AMS radiocarbon dating and stable isotope analyses with the aim of
      improving understanding of the chronological history and ecological setting of
      the two sites. Previously published radiocarbon dates appeared to indicate that
      the earliest Magdalenian occupation at Gonnersdorf fell around 12,900
      uncalibrated (14)C yr BP, while the earliest occupation at Andernach may have
      been more than 500 radiocarbon years earlier. The AMS determinations presented
      here revise this impression and suggest that the onset of occupation at the two
      sites was in fact simultaneous and prior to the warming of Greenland Interstadial
      GI 1e. At Gonnersdorf, a chronological hiatus exists between the main Magdalenian
      faunal assemblage and mega-faunal remains interpreted as collected sub-fossil
      material. At Andernach-Martinsberg, there is a clear chronological hiatus between
      the Magdalenian occupation and subsequent Federmessergruppen activities at the
      site. However, an intermediate radiocarbon date on an atypically preserved horse
      bone is suggestive of ephemeral human visits to the site between these well
      demonstrated phases. A date of similar age on an elk bone from Gonnersdorf may
      indicate broadly contemporaneous human presence at Gonnersdorf too. Stable
      isotope analysis of faunal remains from Gonnersdorf and Andernach-Martinsberg was
      conducted with the aim of both reconstructing and comparing local environmental
      conditions at the two sites, and also potentially identifying subtle variations
      in the chronological development of the two sites not detectable at the level of
      precision of current radiocarbon dating techniques. No spatial trends in the
      faunal isotope signatures were observed within each site. In the case of samples
      with both radiocarbon and isotope data, no chronological pattern was observed for
      the isotope results. The Magdalenian faunal isotope signatures at the two sites
      resembled each other, suggesting comparable climatic and environmental
      conditions. The faunal delta(13)C signatures at Gonnersdorf and Andernach
      Martinsberg were similar to those at contemporary European sites. While the
      faunal delta(15)N values were similar to those at contemporary sites in Germany,
      the UK, and Belgium, they were lower than those from the South of France. This
      difference in delta(15)N values is thought to relate to regional differences in
      the timing of changes in soil and plant nitrogen cycling in response to
      ameliorating climatic conditions.

PMID- 19589559
TI  - Liang Bua Homo floresiensis mandibles and mandibular teeth: a contribution to the
      comparative morphology of a new hominin species.
AB  - In 2004, a new hominin species, Homo floresiensis, was described from Late
      Pleistocene cave deposits at Liang Bua, Flores. H. floresiensis was remarkable
      for its small body-size, endocranial volume in the chimpanzee range, limb
      proportions and skeletal robusticity similar to Pliocene Australopithecus, and a
      skeletal morphology with a distinctive combination of symplesiomorphic, derived,
      and unique traits. Critics of H. floresiensis as a novel species have argued that
      the Pleistocene skeletons from Liang Bua either fall within the range of living
      Australomelanesians, exhibit the attributes of growth disorders found in modern
      humans, or a combination of both. Here we describe the morphology of the LB1,
      LB2, and LB6 mandibles and mandibular teeth from Liang Bua. Morphological and
      metrical comparisons of the mandibles demonstrate that they share a distinctive
      suite of traits that place them outside both the H. sapiens and H. erectus ranges
      of variation. While having the derived molar size of later Homo, the symphyseal,
      corpus, ramus, and premolar morphologies share similarities with both
      Australopithecus and early Homo. When the mandibles are considered with the
      existing evidence for cranial and postcranial anatomy, limb proportions, and the
      functional anatomy of the wrist and shoulder, they are in many respects closer to
      African early Homo or Australopithecus than to later Homo. Taken together, this
      evidence suggests that the ancestors of H. floresiensis left Africa before the
      evolution of H. erectus, as defined by the Dmanisi and East African evidence.

PMID- 19589560
TI  - Early colonization of stone by freshwater lichens of restored habitats: a case
      study in northern Italy.
AB  - This study evaluated the effectiveness and life-strategies of freshwater lichens
      in colonizing newly constructed stone structures in low-elevation streams in a
      small nature reserve in northern Italy. Species richness, size of thalli,
      morphological and ontogenetic traits of the species were related to the age of
      restored habitats. Lichen colonization was surprisingly rapid, indicating the
      high potential of these organisms in colonizing restored habitats. However, the
      species pool found in the restored habitats was different than that found in
      natural sites in the same study area. The age of newly constructed habitats
      influenced both species richness and thallus size of the two most frequent
      Verrucaria species. Verrucaria aquatilis was a rapid colonizer invading the
      substrate by several small-sized and thin thalli which soon supported a large
      number of small perithecia whose development began in the earlier phase of
      thallus formation. V. elaeomelaena, on the contrary, developed according to a
      different strategy, establishing a thick thallus on which relatively large
      perithecia were formed much later than in V. aquatilis. As these taxa are
      important photoautotrophic components of freshwater ecosystems more ecological
      knowledge is needed to evaluate the effectiveness of different measures of river
      restoration on lichen communities. The main practical implication of our study is
      related to the value of small stone structures, such as riffles and ramps, for
      enhancing the establishment of pioneer freshwater lichens to rapidly colonize
      newly available substrata.

PMID- 19589561
TI  - Primary osteoarthritis no longer primary: three subsets with distinct
      etiological, clinical, and therapeutic characteristics.
AB  - BACKGROUND: Osteoarthritis (OA) has been historically divided into primary and
      secondary. Primary OA has been defined as an idiopathic condition developing in
      previously undamaged joints in the absence of an obvious causative mechanism.
      During the last few years a large amount of evidence has provided new insights
      into the biochemistry and molecular biology of cartilage, subchondral bone, and
      other articular tissues, which suggest distinct etiopathogenetic mechanisms in
      some forms of primary OA. OBJECTIVE: To propose an etiopathogenic classification
      of primary OA in the light of the significant progress in the understanding of
      the disease. METHODS: A review of the literature was performed by searching the
      Medline and PubMed databases from 1952 to November 2008 using the following
      keywords: genetic alteration, heritability, estrogen, menopause, and aging either
      alone or in various combinations with joint, cartilage, subchondral bone,
      synovium, ligaments, muscle, tendons, OA, and osteoporosis. RESULTS: Numerous
      studies have shown that genetic alterations, menopause-related estrogen
      deficiency, and aging play crucial roles in the molecular pathophysiological
      events involved in the process of cartilage and joint damage and thus in
      development of OA. We propose classifying primary OA into 3 distinct although
      interrelated subsets: type I OA, genetically determined; type II OA, estrogen
      hormone dependent; and type III OA, aging related. CONCLUSIONS: The 3 proposed
      subsets of OA display distinct etiological, clinical, and therapeutic
      characteristics and should therefore no longer be considered to be "Primary OA."

PMID- 19589562
TI  - Immunolocalization of FGF1 and FGF2 in the regenerating tail of the lizard
      Lampropholis guichenoti: implications for FGFs as trophic factors in lizard tail
      regeneration.
AB  - A role for fibroblast growth factors in stimulating limb and tail regeneration in
      amphibians has been shown; however, it is unknown whether these growth factors
      are also involved in the regeneration of the tail of lizard, an amniote model for
      studies on tissue regeneration. The presence of fibroblast growth factor-1 (FGF1)
      and -2 (FGF2) in the regenerating tail of the lizard Lampropholis guichenoti has
      been studied using immunofluorescence labeling. The study reveals that FGF2 is
      mainly localized in the wound and scaling epidermis, in differentiating muscles,
      in spinal ganglia, regenerating nerves and spinal cord. FGF1 is also present in
      the wound and differentiating epidermis, but is detectable at lower levels in the
      regenerating muscles and spinal cord. FGF1 is present in blastema cells, while
      FGF2 labeling is relatively low in these cells. Fibroblasts of the forming dermis
      are rich in FGF1 but not in FGF2. Developing blood vessels label for both FGF1
      and FGF2 while the cartilaginous, bone and fat tissues are poorly labeled or
      unlabeled for FGFs. The present study suggests that most FGFs in the regenerating
      tail are located in the nervous system, in the epidermis and muscles, and these
      tissues most likely require these growth factors for their differentiation and
      growth. The present study suggests that FGFs produced in the regenerating
      epidermis, spinal cord and nerves can stimulate tail regeneration in lizards.

PMID- 19589563
TI  - Change in contralateral renal parenchymal volume 1 week after unilateral
      nephrectomy.
AB  - OBJECTIVES: To measure the contralateral renal parenchymal volume (RPV) before
      and after nephrectomy and investigate the factors influencing compensatory
      hypertrophy. Unilateral nephrectomy induces compensatory hypertrophy in the
      contralateral kidney. METHODS: From December 2003 to January 2008, 142 patients
      undergoing nephrectomy were enrolled in this study. All patients underwent
      preoperative technetium-99m dimercaptosuccinic acid renal scintigraphy. The
      percentage of technetium-99m dimercaptosuccinic acid uptake in the resected
      kidney was 37.2% +/- 15.3%. Contrast-enhanced computed tomography was performed
      preoperatively and 1 week and 6 months postoperatively, and RPV was calculated as
      the normally functioning tissue, excluding tumors or nonenhanced areas. RESULTS:
      The mean RPV of the remaining kidney was 164.2 cm(3) preoperatively and 184.1 and
      178.8 cm(3) at 1 week and 6 months postoperatively, respectively. Multivariate
      regression analysis revealed that the increase in RPV was positively associated
      with the percentage of technetium-99m dimercaptosuccinic acid uptake in the
      resected kidney (P < .001) and negatively associated with patient age (P = .008).
      Logistic regression analysis showed that the group with an RPV increase of <15%
      had a 4.1-fold increased risk of a 10% decrease in the glomerular filtration rate
      during the next 6 postoperative months compared with the risk in the group with
      an RPV increase of >or=15% (P = .004). CONCLUSIONS: The change in contralateral
      RPV occurred during the first week after nephrectomy and remained stable for
      >or=6 months. The change in RPV increased when the removed kidney had greater
      function and decreased with increasing patient age. The risk of progression to
      renal insufficiency can be predicted according to the change in RPV.

PMID- 19589565
TI  - Celecoxib in the management of acute renal colic: a randomized controlled
      clinical trial.
AB  - OBJECTIVES: To evaluate the efficacy of celecoxib as an analgesic and medical
      expulsive agent in acute renal colic. METHODS: A prospective randomized double
      blind study was conducted on patients presenting with an obstructing ureteral
      calculus < 10 mm in largest diameter. Patients were randomized to 400 mg of
      celecoxib, followed by 200 mg every 12 hours for 10 days, or to placebo. Patients
      with a solitary kidney, renal insufficiency (CR > 1.8), urinary tract infection,
      or significant cardiovascular disease were excluded. RESULTS: A total of 57
      patients provided consent of which 53 completed the study. Four patients were
      excluded from the analysis because of stone passage or withdrawal of consent
      before the first dose of study medication. No significant difference was noted in
      the spontaneous stone passage rate (celecoxib 55.2%, placebo 54.2%) and between
      celecoxib and placebo with regard to days to stone passage (7.0 vs 9.0, P = .6)
      or size of stone passed (3.9 vs 4.6 mm, P = .18). No significant difference was
      noted in pain analog scores (2.6 vs 3.5, P = .71) or narcotic doses (13.2 vs
      13.6, P = .74). Furthermore, a 25% decrease in narcotic use (or 19 mg based on
      placebo mean) was outside the 80% one-sided confidence interval for the change in
      mean narcotic use between the 2 groups. Thus, it is unlikely (< 20%) that we
      missed a clinically significant beneficial effect of celecoxib on narcotic
      consumption because of sample size. CONCLUSIONS: Celecoxib does not facilitate
      stone passage or decrease narcotic requirements in patients with acute renal
      colic.

PMID- 19589566
TI  - Carcinosarcoma of the prostate replacing the entire lower genitourinary tract.
AB  - Less than 100 cases of prostate carcinosarcoma have been described in published
      studies. Most of these cases describe symptoms due to bladder outlet obstruction
      that typically results in transurethral resection of the prostate. Our patient
      presented with tenesmus and stranguria due to prostate carcinosarcoma that
      developed years after being treated with external radiation and androgen
      deprivation for prostate adenocarcinoma. Because of the patient's escalating
      symptoms, a pelvic exenteration with creation of urinary and fecal diversions was
      performed. Despite the dismal survival associated with prostate carcinosarcoma,
      palliative surgical extirpation can be successful in patients with debilitating
      pain.

PMID- 19589564
TI  - Access to information sources and treatment considerations among men with local
      stage prostate cancer.
AB  - OBJECTIVES: To determine the role of information sources in the treatment
      decision-making process of men diagnosed with local stage prostate cancer.
      Diagnosed men have access to a large number of information sources about therapy,
      including print and broadcast media, the Internet, books, and friends with the
      disease. METHODS: Prospective survey of men with local stage prostate cancer in 3
      geographically separate regions was carried out. Most men were surveyed after
      diagnosis but before starting therapy. RESULTS: On average, men with local
      prostate cancer consulted nearly 5 separate sources of information before
      treatment. The most common source of information was the patient's physician
      (97%), followed by lay-literature (pamphlets, videos) (76%), other health
      professionals (71%), friends with prostate cancer (67%), and the Internet (58%).
      Most men rated the sources they consulted as helpful. Consulting the Internet was
      associated with considering more treatment options. Several information sources
      were significantly associated with considering particular treatments, but the
      magnitude of association was small in relation to patient age, comorbidity, and
      Gleason score. More than 70% of men stated that they were considering or planning
      only one type of therapy. CONCLUSIONS: Men with local stage prostate cancer
      consult a wide range of information sources. Nonphysician information sources
      appear to influence their treatment considerations, but to a smaller degree than
      clinical factors.

PMID- 19589567
TI  - Advances in molecular genetics of cryptorchidism.
AB  - Cryptorchidism is the most common congenital disorder in boys; one major
      complication of this disorder is male infertility. Androgens are key hormones to
      complete testicular descent; therefore, impaired fetal androgen action can result
      in this anomaly; its molecular etiology, however, remains unknown. Recent
      molecular approaches might provide an opportunity to identify not only candidate
      genes but also several predictive markers of future fertility. The purpose of
      this review is to summarize the recent insight into the genetic pathway of
      testicular descent and the molecular etiology of isolated cryptorchidism, and
      discuss the prospects of treatment to achieve future fertility in such patients.

PMID- 19589568
TI  - Significant change in predicted risk of biochemical recurrence after radical
      prostatectomy more common in black than in white men.
AB  - OBJECTIVES: To examine by race how frequently the data after radical
      prostatectomy translates into a substantial change in prognosis. Many nomograms
      exist to predict the survival outcomes using the pretreatment clinical parameters
      and post-treatment pathologic parameters. Race might be an important factor
      affecting their predictive ability. METHODS: Kattan nomograms were used to
      calculate the pretreatment and post-radical prostatectomy 5-year progression-free
      probability for each patient. The difference between the nomogram scores was used
      to divide the patients into 3 groups. A decrease in probability of >or=15
      percentage points was classified as a significant increase in the probability of
      recurrence, an increase of >or=15 points was classified as a significant decrease
      in the probability of recurrence, and an absolute change of <15 points was
      considered no significant change. RESULTS: The data from 1709 (132 black and 1577
      white) men were analyzed. Among the black men, 26.5% had an increase in the
      probability of recurrence, 57.6% had no change, and 15.9% had a decrease in the
      probability of recurrence. Among the white men, 13.8% had an increase in the
      probability of recurrence, 64.5% had no change, and 21.7% had a decrease in the
      probability of recurrence. Black men were twice as likely to have a significant
      increase in the probability of recurrence postoperatively compared with white men
      after adjusting for preoperative prostate-specific antigen level, clinical stage,
      and biopsy Gleason sum (odds ratio 2.0, 95% confidence interval 1.3-3.1, P =
      .002). CONCLUSIONS: These data could assist clinicians when counseling black men
      regarding their treatment options according to their preoperative risk profile.

PMID- 19589569
TI  - The COMPARE Registry: design and baseline patterns of care for men with
      biochemical failure after definitive treatment of localized prostate cancer.
AB  - OBJECTIVES: To define current standards of care for patients with prostate
      specific antigen (PSA) failure after initial definitive local treatment of
      prostate cancer using Comprehensive, Observational, Multicenter, Prostate
      Adenocarcinoma Registry (COMPARE). This article describes the design of the
      COMPARE Registry, together with patient characteristics and prostate cancer
      management at enrolment. METHODS: The COMPARE Registry is a prospective,
      multicenter, observational study that collected data on patient characteristics,
      management practices, and outcomes of men presenting to their physician for the
      management of an increasing PSA level after definitive (surgical or
      radiotherapeutic) treatment of localized prostate cancer. Data collected by the
      physician and reported by the patient at the baseline (enrolment) visit are
      described. RESULTS: Between February 2004 and March 2007, 1120 men were enrolled
      at 150 sites throughout the United States. The men had a median age of 73 years
      (range, 46-95 years), were predominantly white (77%), and had a median PSA level
      of 7.9 ng/mL (range, 0-710.8 ng/mL) at diagnosis. Observation (74%) was the most
      common initial management choice at registry enrolment, and androgen-deprivation
      therapy (22%) was the most common initial treatment choice. CONCLUSIONS: Data
      from the COMPARE Registry should provide a valuable source of prospectively
      collected information on the contemporary management of prostate cancer and
      patient outcomes after PSA failure.

PMID- 19589570
TI  - Thick curved planar reformation of unenhanced multislice computed tomography
      demonstrating urolithiasis.
AB  - OBJECTIVES: To determine what slice thickness provides optimal curved planar
      reformation (CPR) images of the urinary tract. METHODS: A total of 75 consecutive
      patients with acute flank pain were included in a retrospective pilot study and
      underwent unenhanced multislice computed tomography (MSCT) (collimation 3.75 mm,
      pitch 6, reconstruction increment 3 mm, working voltage 120 kV, and tube current
      100 mA) with CPR reconstruction of the urinary tract. CPRs with differing slice
      thicknesses of 3-20 mm at 1-mm increments to reformat each ureter were assessed
      in each patient separately. Two radiologists and a urologist evaluated the
      quality of the reformatted images by judging each ureter in terms of the
      delineation of all its parts using a 5-point scale (insufficient, poor, moderate,
      good, and excellent). RESULTS: Of the 75 patients in our cohort, 52 (69%) had
      urolithiasis. CPR images could be made of all ureters in all patients. Good to
      excellent image quality was found in the CPRs performed with a slice thickness of
      8-12 mm: 27.7% at 8 mm, 14.3% at 9 mm, 26.9% at 10 mm, 12.6% at 11 mm, and 18.5%
      at 12 mm. Thus, a slice thickness of 8-12 mm determined a cumulative likelihood
      of 96.7% to demonstrate the ureter totally. CONCLUSIONS: The results of our study
      have shown that CPR is a feasible and quick useful tool. CPRs of the urinary
      tract with a slice thickness of 8-12 mm are best for good delineation of the
      whole ureter.

PMID- 19589571
TI  - Clear cell "sugar" tumors of urethra: a previously undescribed occurrence and
      review of published data.
AB  - Clear cell "sugar" tumor is a rare benign tumor considered as a member of the
      family of perivascular epithelioid cell tumors. To the best of our knowledge,
      this is the first case of clear cell "sugar" tumor presented as a mass protruding
      from the urethra in a 15-year-old girl. Pathologic examination revealed a tumor
      composed of epithelioid cells with "water" clear cytoplasm that stained
      positively for melanocytic and smooth muscle-specific markers. Treatment of this
      tumor included a surgical excision and complete removal of the urethral mass,
      with examination of surgical margins. Three months after surgery, the patient
      remains clinically free of disease.

PMID- 19589572
TI  - Anatomic restoration technique: a biomechanics-based approach for early
      continence recovery after minimally invasive radical prostatectomy.

PMID- 19589574
TI  - Nonoperative management of nonvascular grade IV blunt renal trauma in children:
      meta-analysis and systematic review.
AB  - OBJECTIVES: To evaluate nonoperative management of grade IV blunt renal trauma in
      pediatric patients by performing a systematic review and meta-analysis of
      published studies. METHODS: MEDLINE, EMBASE, Cochrane, and Scopus databases were
      searched between January 1992 and June 2008 for studies of pediatric renal trauma
      management. Inclusion criteria were patient age <or= 18 years and use of the
      American Association for the Surgery of Trauma renal injury scale. RESULTS: A
      total of 95 children with grade IV injuries were identified. No intervention was
      required in 72% (68/95). Hemodynamic instability necessitated surgical
      exploration in 11% of patients (11/95). Of these, 46% (5/11) required a partial
      nephrectomy, 27% (3/11) underwent nephrectomy, and 27% (3/11) were salvaged.
      Angiographic infarction was not used for patients with delayed or persistent
      hemorrhage. Symptomatic urinoma developed in 17% (16/95). Of these patients, 81%
      (13/16) were successfully managed by percutaneous drainage or ureteral stent
      placement, and open intervention to manage complications became necessary in the
      remaining 19% (3/16). Partial renal preservation was possible in 95% of patients
      (90/95). CONCLUSIONS: Nonoperative management of children with grade IV blunt
      renal injuries is highly successful, with at least partial renal preservation
      possible in 95% (90/95) of patients.

PMID- 19589573
TI  - Responsiveness of the University of California-Los Angeles Prostate Cancer Index.
AB  - OBJECTIVES: To determine the responsiveness of the University of California-Los
      Angeles Prostate Cancer Index (UCLA-PCI) by studying its sensitivity to
      clinically perceptible changes in health over time in men treated for localized
      prostate cancer. METHODS: All subjects underwent radical prostatectomy (n=253),
      external beam radiotherapy (n=66), or interstitial seed brachytherapy (n=73). We
      assessed health-related quality of life (HRQOL) outcomes using the UCLA-PCI to
      capture disease-specific outcomes and the Medical Outcomes Study Short Form-36 to
      study general HRQOL. We assessed the UCLA-PCI's responsiveness to change by
      comparison with the health change item of the Medical Outcomes Study Short Form
      36. We measured responsiveness by calculating effect sizes and Guyatt statistics
      when comparing UCLA-PCI scores between baseline and 1 year and between 1 and 2
      years. RESULTS: Of the 475 men who completed all baseline questionnaires, 392
      (83%) completed all surveys at 12-month follow-up. Although sexual function
      decreased from baseline to 12 months in all groups, the magnitude of the negative
      change was inversely proportional to general health. For those whose general
      health worsened, effect sizes were >0.50 across all 6 domains. Effect sizes and
      Guyatt statistics were lowest (<0.25) for urinary bother, bowel function, and
      bowel bother in the groups demonstrating either no change or improvement in
      general health. Responsiveness of the UCLA-PCI in the short-term recovery period
      (12 months post-treatment) was better than in the chronic recovery phase (12-24
      months) across almost all domains. CONCLUSIONS: The UCLA-PCI is responsive to
      change in assessing HRQOL in men treated for prostate cancer.

PMID- 19589575
TI  - Evaluation of the hemostatic and coagulation effects of AUTO CUT and DRY CUT
      using a computer-controlled cutting system.
AB  - OBJECTIVES: To evaluate a newly developed computer-controlled cutting system for
      the generation of standardized resections and to systematically compare the
      hemostatic properties and tissue effect of 2 cutting modes, namely, AUTO CUT and
      DRY CUT used in urologic procedures. METHODS: An isolated perfused kidney model
      was used to assess blood loss and coagulation depth after resection of tissue
      specimens of standardized geometry, size, and cutting velocity with a resection
      loop. Three different effect settings (E1, E3, and E6; 200 W) of the
      electrosurgical modes AUTO CUT and DRY CUT were compared. Blood loss was
      determined semiquantitatively by weighing a swab before and after placing it onto
      the resection area. The coagulation depth was estimated microscopically on cross
      sections. RESULTS: The computer-controlled cutting system creates resections of
      standardized geometry and size with a high reproducibility. An effect level
      dependent increase in hemostasis and coagulation depth could be demonstrated with
      the cutting modes DRY CUT and AUTO CUT using this computer-controlled cutting
      system. The hemostatic effect with DRY CUT is significantly more pronounced than
      with AUTO CUT (E1, E3: P < .0001, E6: P = .004), and the coagulation is
      significantly deeper (E1, E3, E6: P < .0001). CONCLUSIONS: The computer
      controlled cutting system creating reproducible resections in combination with
      the isolated perfused kidney model offers the possibility to systematically
      investigate bleeding rate and coagulation depth. The stronger hemostatic
      properties of the DRY CUT mode are more favorable for urologic interventions
      requiring a higher hemostatic effect than the AUTO CUT mode.

PMID- 19589576
TI  - Seminal vesicle metastasis of renal cell carcinoma.
AB  - We present an unusual magnetic resonance imaging finding of a 70-year-old man
      with the seminal vesicle tumor. The patient underwent radical nephrectomy for
      renal cell carcinoma 4 years ago. Laboratory data, including prostatic-specific
      antigen, ranged within normal limits. Transrectal needle biopsy disclosed a clear
      cell carcinoma, which was compatible with the original renal cell cancer.
      Vesiclectomy was performed. Pathohistologic examination confirmed a metastatic
      renal cell carcinoma of the seminal vesicle.

PMID- 19589577
TI  - Management of non-neoplastic renal hemorrhage by transarterial embolization.
AB  - OBJECTIVES: To assess the role of transarterial embolization (TAE) and critically
      appraise its feasibility and efficacy in the management of non-neoplastic renal
      hemorrhage. Percutaneous TAE is an effective method for the control of
      hemorrhage, irrespective of the cause. Injury to the renal artery or its branch,
      after trauma or during open or percutaneous urologic procedures, can be
      accurately diagnosed using angiography and treated by percutaneous embolization
      techniques. Because the technique and technology have evolved, it is now possible
      to perform highly selective embolization of the injured vessel while preserving
      vascularity of the rest of the renal parenchyma. METHODS: The medical records of
      all patients who underwent angioembolization for hemorrhagic urologic emergencies
      at our institute from January 1996 to December 2007 were reviewed. RESULTS: A
      total of 41 patients, aged 7-72 years, underwent TAE because of hemorrhage after
      percutaneous nephrolithotomy (n = 27), open pyelolithotomy (n = 3), renal biopsy
      (n = 8), and spontaneous occurrence (n = 3). All patients had a normal
      coagulation profile before surgery. A total of 35 patients (85.3%) underwent
      successful embolization and none required a postprocedural blood transfusion. Of
      those with postpercutaneous nephrolithotomy bleeding, angioembolization failed in
      6 patients. Of these, only 2 required nephrectomy to save the patient's life. No
      serious procedure-related complications occurred. CONCLUSIONS: TAE is a minimally
      invasive, safe, simple, and highly effective modality, in expert hands, for the
      management of postprocedural renal bleeding. This option should be considered
      early in the management of these cases because it is not only a life-saving, but
      ultimately a kidney-sparing, procedure.

PMID- 19589578
TI  - Laparoscopic radical prostatectomy in renal transplant recipients.
AB  - OBJECTIVES: To report our experience with 9 consecutive laparoscopic radical
      prostatectomy (LRP) on renal transplant recipients (RTR) and to compare it with
      other LRPs performed during the same period by the same surgeons. Retropubic
      radical prostatectomy has widely been described in RTR, whereas LRP has rarely
      been studied. METHODS: Between January 2007 and December 2008, all clinical data
      from patients undergoing radical prostatectomy were prospectively collected in a
      database. The database was searched to find information of LRP on RTR. We
      compared RTR and other patients for all relevant clinical data and for surgical
      complications. RESULTS: A total of 9 LRP on RTR (5.8%) and other 164 LRP were
      performed. LRP on RTR were compared with other LRP. No statistically relevant
      difference was observed in patient characteristics, biopsy core pathologic
      analysis, prostate specimen pathologic analysis, and oncologic outcomes. Surgical
      procedure was also achieved under the same conditions in RTR than in other
      patients (surgical time, blood loss, transfusion rate, bladder injury). Rectal
      injury rate was significantly higher in RTR than in other patients (22.2% vs
      1.8%, P = .022). CONCLUSIONS: LRP in RTR is feasible. The procedure can be
      managed the same way as LRP on other patients, but special care must be taken to
      avoid rectal injury. In our experience, the dissection of the posterior side of
      the prostate was more difficult on RTR than on other patients.

PMID- 19589579
TI  - Megalourethra with calculi.
AB  - Megalourethra is a rare congenital malformation of the urethra. Multiple
      associated anomalies have been noted in the cases reported thus far. However,
      none of the cases reported showed associated calculi either in the megalourethra
      or elsewhere in the urinary tract. A case of scaphoid megalourethra is presented
      here to illustrate the unique presence of multiple calculi in the megalourethra.

PMID- 19589580
TI  - Urinary side effects and complications after permanent prostate brachytherapy:
      the MD Anderson Cancer Center experience.
AB  - OBJECTIVES: To evaluate acute and long-term urinary morbidity after permanent
      prostate brachytherapy at a single tertiary care center. To minimize the risk of
      long-term urinary morbidity, it is important for clinicians to be able to
      distinguish acute urinary side effects after prostate brachytherapy from longer
      term treatment-related urinary complications. METHODS: The medical records of 351
      consecutive patients who underwent prostate brachytherapy at the MD Anderson
      Cancer Center between 1998 and 2006 were analyzed. To evaluate the short-term
      urinary side effects, the Expanded Prostate Cancer Index Composite questionnaire
      was administered at baseline and at 1, 4, 8, and 12 months. Long-term urinary
      complications were scored using a modified Radiation Therapy Oncology Group
      scale. RESULTS: All 4 urinary subdomain scores evaluating acute urinary side
      effects after treatment (bother, function, incontinence, and irritation or
      obstruction) had returned to baseline levels by 8 months after implantation. At 5
      years, the cumulative risks of late urinary complications by grade were 8.6% for
      grade 1 complications, 6.5% for grade 2, 1.7% for grade 3%, and 0.5% for grade 4.
      The most common grade 2 late urinary complications were urethral stricture (4
      patients), incontinence requiring daily pads (3 patients), and intermittent
      hematuria (3 patients). Grade 3 complications were urinary retention requiring
      self-catheterization (2 patients) and severe frequency with dysuria (2 patients).
      The only grade 4 event was severe hemorrhagic cystitis. CONCLUSIONS: Short-term
      urinary side effects after prostate brachytherapy are common, follow a
      predictable course, and typically resolve within 1 year. Conservative management
      of short-term urinary side effects is recommended to minimize the risk of long
      term urinary complications.

PMID- 19589581
TI  - Completely separated scrotum and vesicointestinal fistula without exstrophy as a
      novel manifestation of aphallia: a case report.
AB  - A male infant born at 32 weeks of gestation and weighing 1.44 kg had penile
      agenesis, bifid scrotums, an anorectal anomaly, and suspected omphalocele. An
      operation revealed complete urethral agenesis, duplicated and blind bowels, a
      vesicointestinal fistula without exstrophy, and a urachal fistula; however, no
      omphaloceles were detected. To our knowledge, this is the first report on
      aphallia accompanied with completely separated scrotum and a vesicointestinal
      fistula without exstrophy; this condition is associated with urorectal septum
      malformation sequence (URSMS) and covered cloacal exstrophy. The possible
      embryogenesis is discussed in this study.

PMID- 19589582
TI  - Androgen deficiency symptoms in testicular cancer survivors are associated with
      sexual problems but not with serum testosterone or therapy.
AB  - OBJECTIVES: To investigate the association between androgen deficiency symptoms
      and sexual function, serum testosterone, and therapy in testicular cancer
      survivors (TCS). METHODS: A total of 83 patients treated for testicular cancer
      were investigated. All patients completed the International Index of Erectile
      Function-15 and the Aging Males Symptoms scale. Age, months of follow-up,
      treatment modality, and serum testosterone levels were measured. Scores for the
      erectile function, orgasmic function, sexual desire, intercourse satisfaction,
      and overall satisfaction subdomains of the International Index of Erectile
      Function-15 were calculated. RESULTS: Overall, almost half (47.0%) of TCS
      experienced clinical symptoms of androgen deficiency, 28.9% had erectile
      dysfunction, and 25.3% had laboratory-proven hypogonadism. TCS with clinical
      symptoms of androgen deficiency were significantly older (median age 45.0 vs 37.5
      years, P = .001) and had a longer follow-up (median follow-up 48.0 vs 39.5
      months, P = .985, respectively) than TCS without symptoms. TCS with clinical
      symptoms had significantly lower scores for erectile function (P = .004),
      orgasmic function (P = .05), sexual desire (P = .001), intercourse satisfaction
      (P = .005), and overall satisfaction (P = .001) than those without symptoms. The
      aging males' symptoms correlated significantly with erectile dysfunction (r = 
      0.410, P = .001). In TCS with symptoms, age (r = -0.457, P = .003), but not
      treatment modalities (r = 0.223, P = .173) or testosterone levels (r = 0.205, P =
      .210), correlated with sexual function. CONCLUSIONS: Clinical symptoms of
      androgen deficiency were associated with sexual problems and increasing age, but
      not with serum testosterone or treatment.

PMID- 19589583
TI  - Motion corrected cadence CPS ultrasound for quantifying response to vasoactive
      drugs in a rat kidney model.
AB  - OBJECTIVE: To establish the ability of contrast-enhanced motion corrected cadence
      pulse sequencing (CPS) to detect changes in renal blood flow induced by
      vasoactive substances in rats. METHODS: Ultrasound contrast media was
      administered as a constant rate infusion into a phantom at a known rate and CPS
      data acquired. Rats were anesthetized and predrug CPS estimates of replenishment
      rate were made for the right kidney. Real-time motion correction was applied, and
      parametric images were generated from the CPS data. Group 1 rats (n = 7) were
      administered a vasodilator and group 2 rats (n = 3) were administered a
      vasoconstrictor. The CPS imaging of the kidney was repeated after ample time for
      drug effects to occur. RESULTS: Contrast CPS accurately estimated flow velocity
      in the phantom model. In addition, CPS defined statistically significant
      differences between pre- and postdrug blood flow in the renal medulla
      (vasodilator, P < .01; vasoconstrictor, P < .0001) and cortex (vasoconstrictor, P
      < .0001). CONCLUSIONS: We conclude that motion-corrected CPS ultrasound provides
      real-time quantification of renal blood flow alterations and may prove useful for
      the assessment of blood flow in transplanted kidneys.

PMID- 19589584
TI  - Validation of two preoperative Kattan nomograms predicting recurrence after
      radical prostatectomy for localized prostate cancer in Turkey: a multicenter
      study of the Uro-oncology Society.
AB  - OBJECTIVES: To examine, in a multicenter validation study designed under the
      guidance of the Uro-Oncology Society, the predictive accuracies of the 1998 and
      2006 Kattan preoperative nomograms in Turkish patients. These 2 preoperative
      Kattan nomograms use preoperative parameters to estimate disease recurrence after
      radical prostatectomy. METHODS: A total of 1261 men with clinically localized
      prostate cancer undergoing radical prostatectomy were included. The preoperative
      prostate-specific antigen level, biopsy Gleason score, clinical stage, number of
      positive and negative prostate biopsy cores, and postoperative recurrence status
      of all patients were studied. The predicted values using the Kattan nomograms and
      the observed values were compared. RESULTS: The patient characteristics in the
      cohort were comparable with those of the cohorts used to create the Kattan
      nomograms. The 5-year probability of freedom from recurrence was 73% using Kaplan
      Meier analysis and was similar to that of the 1998 Kattan nomogram cohort.
      However, the 10-year probability of freedom from recurrence was 67%, slightly
      lower than the same estimate from the 2006 nomogram cohort. The predicted values
      of recurrence using Kattan nomogram and the observed rates in our cohort were
      similar. The estimated concordance index value was 0.698 and 0.705 for 1998 and
      2006 nomograms, respectively. CONCLUSIONS: The Kattan preoperative nomograms can
      be used with adequate success in Turkey, because the predicted and observed rates
      in our cohort were similar. Our results have demonstrated satisfactory
      concordance index values, suggesting that both the 1998 and the 2006 Kattan
      preoperative nomograms can safely be used in Turkish patients with similar
      accuracy. Although the 2006 nomogram had slightly better discrimination, the 1998
      nomogram was a little more calibrated.

PMID- 19589586
TI  - Collection and characterization of semen in Mithun (Bos frontalis) bulls.
AB  - The objective of this study was to collect semen from semiwild Mithun (Bos
      frontalis) bulls using an artificial vagina (AV) and to determine semen
      characteristics. Collection of semen with an AV was attempted in five Mithun
      bulls using both anestrous and estrous Mithun females. No Mithun bull mounted an
      anestrous female Mithun during 60 trials, but satisfactory mounting, including
      extension of the penis, occurred in 25 trials with estrous Mithun females. In 15
      of these trials, semen was successfully collected in an AV with an internal
      temperature of 42 to 46 degrees C. However, in 10 trials with an AV with an
      internal temperature of 36 to 40 degrees C, semen was not collected. Mean (+/-
      SEM) intervals to first mount and to ejaculation in the AV were 27.9+/-3.6 sec
      and 113.8+/-6.6 sec, respectively. Semen volume and pH were 3.1+/-0.35 mL and
      6.59+/-0.04, and mean mass activity (scale, 0 to 4), initial sperm motility, live
      sperm count, sperm concentration, total number of sperm in the ejaculate, and
      overall sperm length were 2.2+/-0.3, 78.6+/-2.6%, 80.7+/-2.2%, 710.8+/-66.8 x
      10(6)/mL, 2114+/-364.4 sperm, and 67.9+/-0.6 microm, respectively. The proportion
      of morphologically normal sperm was 80.6+/-0.2%, whereas the proportion with a
      morphologically abnormal head, midpiece, tail, and acrosome were 4.2+/-0.4%,
      1.6+/-0.5%, 6.1+/-1.1%, and 7.1+/-0.9%, respectively. The mean incidence of tail
      less heads and proximal and distal protoplasmic droplets were 0.5+/-0.1%, 0.3+/
      0.2%, and 2.4+/-0.3%, respectively. In conclusion, we successfully collected
      semen from semiwild Mithun bulls with an AV maintained at 42 to 46 degrees C, and
      overall, the semen was within the normal range of that collected from fertile
      domestic bulls.

PMID- 19589587
TI  - Menstrual knowledge and practices of female adolescents in urban Karachi,
      Pakistan.
AB  - Menstruation is a normal physiological process that is managed differently
      according to various social and cultural understandings. Therefore, this cross
      sectional study was conducted to explore the menstrual practices among 1275
      female adolescents of urban Karachi, Pakistan from April to October 2006 by using
      interviews. Data was entered and analyzed in Epi Info Version 9 and SPSS Version
      10. Descriptive findings showed that 50% of the girls lacked an understanding of
      the origin of menstrual blood and those with a prior knowledge of menarche had
      gained it primarily through conversations with their mothers. Many reported
      having fear at the first experience of bleeding. Nearly 50% of the participants
      reported that they did not take baths during menstruation. In univariate
      analysis, factors of using unhygienic material, using washcloths, and not drying
      under sun were found to be significant in the Chi square test among those going
      and not going to schools. This study concludes that there are unhygienic
      practices and misconceptions among girls requiring action by health care
      professionals.

PMID- 19589589
TI  - Unemployment and suicide.

PMID- 19589588
TI  - The public health effect of economic crises and alternative policy responses in
      Europe: an empirical analysis.
AB  - BACKGROUND: There is widespread concern that the present economic crisis,
      particularly its effect on unemployment, will adversely affect population health.
      We investigated how economic changes have affected mortality rates over the past
      three decades and identified how governments might reduce adverse effects.
      METHODS: We used multivariate regression, correcting for population ageing, past
      mortality and employment trends, and country-specific differences in health-care
      infrastructure, to examine associations between changes in employment and
      mortality, and how associations were modified by different types of government
      expenditure for 26 European Union (EU) countries between 1970 and 2007. FINDINGS:
      We noted that every 1% increase in unemployment was associated with a 0.79% rise
      in suicides at ages younger than 65 years (95% CI 0.16-1.42; 60-550 potential
      excess deaths [mean 310] EU-wide), although the effect size was non-significant
      at all ages (0.49%, -0.04 to 1.02), and with a 0.79% rise in homicides (95% CI
      0.06-1.52; 3-80 potential excess deaths [mean 40] EU-wide). By contrast, road
      traffic deaths decreased by 1.39% (0.64-2.14; 290-980 potential fewer deaths
      [mean 630] EU-wide). A more than 3% increase in unemployment had a greater effect
      on suicides at ages younger than 65 years (4.45%, 95% CI 0.65-8.24; 250-3220
      potential excess deaths [mean 1740] EU-wide) and deaths from alcohol abuse
      (28.0%, 12.30-43.70; 1550-5490 potential excess deaths [mean 3500] EU-wide). We
      noted no consistent evidence across the EU that all-cause mortality rates
      increased when unemployment rose, although populations varied substantially in
      how sensitive mortality was to economic crises, depending partly on differences
      in social protection. Every US$10 per person increased investment in active
      labour market programmes reduced the effect of unemployment on suicides by 0.038%
      (95% CI -0.004 to -0.071). INTERPRETATION: Rises in unemployment are associated
      with significant short-term increases in premature deaths from intentional
      violence, while reducing traffic fatalities. Active labour market programmes that
      keep and reintegrate workers in jobs could mitigate some adverse health effects
      of economic downturns. FUNDING: Centre for Crime and Justice Studies, King's
      College, London, UK; and Wates Foundation (UK).

PMID- 19589590
TI  - A survey of indicators for reproductive endocrine disruption in Fundulus
      heteroclitus (killifish) at selected sites in the Chesapeake Bay.
AB  - Plasma vitellogenin and related parameters in the killifish Fundulus heteroclitus
      were measured at selected sites in the Chesapeake Bay. In males, vitellogenin was
      above the detection limit 14% of the time, and detections did not differ between
      sites or seasons. Few differences in plasma vitellogenin levels were found
      between sites during fall in either male or female F. heteroclitus, the time of
      natural gonadal regression for this species. There was some variation in the
      ratio of male to female F. heteroclitus, but was not consistent at most sites.
      Significant negative correlations were found between reported sediment polycyclic
      aromatic hydrocarbons (PAHs) and GSI, and PAHs and plasma vitellogenin in females
      in both Spring 1999 and Spring 2000. Gonadal anomalies in F. heteroclitus
      included slight reductions in certain tissue types. Overall, reproductive
      endocrine disruption in the killifish F. heteroclitus at the sites sampled in the
      Chesapeake Bay appeared somewhat minimal.

PMID- 19589591
TI  - Cellular behavior on TiO2 nanonodular structures in a micro-to-nanoscale
      hierarchy model.
AB  - Biological tissues involve hierarchical organizations of structures and
      components. We created a micropit-and-nanonodule hybrid topography of TiO(2) by
      applying a recently reported nanonodular self-assembly technique on acid-etch
      created micropit titanium surfaces. The size of the nanonodules was controllable
      by changing the assembly time. The created micro-nano-hybrid surface rendered a
      greater surface area and roughness, and extensive geographical undercut on the
      existing micropit surface and resembled the surface morphology of biomineralized
      matrices. Rat bone marrow-derived osteoblasts were cultured on titanium disks
      with either micropits alone, micropits with 100-nm nodules, micropits with 300-nm
      nodules, or micropits with 500-nm nodules. The addition of nanonodules to
      micropits selectively promoted osteoblast but not fibroblast function. Unlike the
      reported advantages of microfeatures that promote osteoblast differentiation but
      inhibit its proliferation, micro-nano-hybrid topography substantially enhanced
      both. We also demonstrated that these biological effects were most pronounced
      when the nanonodules were tailored to a diameter of 300nm within the micropits.
      An implant biomechanical test in a rat femur model revealed that the strength of
      bone-titanium integration was more than three times greater for the implants with
      micropits and 300-nm nanonodules than the implants with micropits alone. These
      results suggest the establishment of functionalized nano-in-microtitanium
      surfaces for improved osteoconductivity, and may provide a biomimetic micro-to
      nanoscale hierarchical model to study the nanofeatures of biomaterials.

PMID- 19589592
TI  - Primary cutaneous diffuse large B-cell lymphoma, leg type, with expression of
      both vascular endothelial growth factor and its receptors.

PMID- 19589593
TI  - JAK2-V617F mutation and Philadelphia positive chronic myeloid leukemia.

PMID- 19589594
TI  - The profile and progress of neglected and abused children in long-term foster
      care.
AB  - OBJECTIVES: This study compared the profile of neglected and abused children in
      the Australian foster care system as well as differences between maltreatment
      types in relation to parental contact, reunification and psychosocial progress in
      care. METHOD: The case files of 235 children entering foster care were examined
      and their social workers were administered standardised questionnaires at the
      point of intake. All measures were repeated for those remaining in care 1 year
      and then again 2 years later. RESULTS: Neglected children were younger than non
      neglected children, more likely to have a physical or mental disability, more
      likely to experience multiple forms of maltreatment and less likely to pose
      conduct problems for carers. Neglected children were more likely than non
      neglected children to experience a decline in parental contact over time, and
      were less likely to be reunified with their families of origin. There was minimal
      difference between neglected and non-neglected in their psychosocial progress
      while in care. Aboriginal children were more likely to be reunified than non
      Aboriginal children when neglect was attributable to transient factors (parental
      incapacity) but the reverse was true for non-neglected children. CONCLUSIONS: The
      fact that neglected children more often require a second form of maltreatment
      before being removed from home suggests that children's services workers are less
      inclined to remove children for neglect than for other forms of maltreatment. As
      a consequence, those neglected children who are in care tend to come from more
      dysfunctional families than non-neglected children do, as evidenced by the
      relatively poorer parental contact and reunification results of neglected
      children. PRACTICE IMPLICATIONS: Neglected children differ systematically from
      non-neglected children and suffer relative disadvantage in relation to multiple
      forms of maltreatment, parental contact, and reunification. The fact that
      declines in parental contact among neglected children in care occurred only when
      indirect contact was provided suggests that, wherever possible, care plans should
      include face-to-face visits and overnight stays rather than being restricted to
      less direct forms of contact. The difference in the success of reunification
      according to type of neglect (chronic or transient) also suggests that parental
      intervention programs need to focus their efforts on chronic factors rather than
      transient parental factors.

PMID- 19589595
TI  - Men who were sexually abused in childhood: coping strategies and comparisons in
      psychological functioning.
AB  - OBJECTIVE: Coping strategies of men who were sexually abused in childhood were
      examined to ascertain their relationship to clinical diagnoses. Time elapsed
      since the abuse occurred was examined for its relationship to psychological
      functioning. Clinical psychopathology of this primary sample of sexually abused
      men was compared to a community sample of men. METHODS: A primary sample of 147
      Australian men was recruited from agencies and self-help groups who support
      adults who were sexually abused in childhood. For comparative purposes a
      secondary data set that consisted of 1,231 men recruited randomly in an
      Australian community survey was utilized. Both samples were administered the 28
      item General Health Questionnaire (GHQ28). The primary sample was administered
      the 60-item coping style inventory instrument (COPE). RESULTS: Coping strategies
      influenced the possibility of being classified as clinical or nonclinical. The
      most important strategies associated with better functioning were positive
      reinterpretation and growth and seeking instrumental social support. Whereas
      strategies that were more associated with a clinical outcome were themed around
      internalization, acceptance and disengagement. The sample of men who were
      sexually abused in childhood was up to 10 times more likely to be classified as
      "clinical" then the sample of community men. Time elapsed since the abuse
      occurred did not have a moderating effect on men's psychological functioning.
      CONCLUSIONS: Men who have been sexually abused in childhood are more likely to
      have clinical diagnoses but coping strategies may play an important part in this
      outcome. Seeking active assistance appears to be important coping strategy in
      reframing the experience, however, the timing of this help seeking is not
      critical. PRACTICE IMPLICATIONS: The findings reinforce the importance of
      professionals being aware that men's psychiatric symptoms might be the sequel to
      past child sexual abuse. Coping strategies that focus on internalization or
      disengagement are potentially damaging to the men's long-term psychological
      functioning. Importantly there are coping strategies that appear to have a
      moderating effect on clinical diagnoses. Focus needs to be given to support
      services to male victims that provide practical strategies and allow for
      cognitive reframing to assist men to see their strength and positive growth
      arising from survival.

PMID- 19589596
TI  - Lifetime assessment of poly-victimization in a national sample of children and
      youth.
AB  - OBJECTIVE: To use a lifetime assessment of victimization experiences to identify
      children and youth with high cumulative levels of victimization (poly-victims).
      Also to compare such children to other victims and non-victims, and assess the
      contribution of cumulative victimization to levels of psychological distress.
      DESIGN: A national sample of 1,467 children aged 2-17 recruited through random
      digit dialing and assessed via telephone interviews (with caretakers and youth
      themselves) about a comprehensive range of 33 types of victimization experiences
      in the previous year and at any time in their lives. RESULTS: Nearly 80% of the
      children and youth reported at least one lifetime victimization. The mean number
      of lifetime victimizations was 3.7 and the median 2.6. The total number of
      different lifetime victimizations was highly predictive of symptoms of current
      distress. The best linear prediction of distress on the basis of cumulative
      victimization entailed weighting child maltreatment and sexual assault by factors
      of 4 and 3 respectively compared to other victimizations. We proposed classifying
      poly-victims as those 10% of children and youth with the highest victimization
      scores, and calculating different thresholds for children at different ages. Poly
      victims designated in this way had significantly more distress, more non
      victimization adversities than other youth and were less likely to come from an
      intact family. CONCLUSION: Lifetime assessment of victimization has value as a
      means of identifying groups of highly victimized children and youth. PRACTICE
      IMPLICATIONS: This paper describes a procedure under which practitioners can
      assess for a group of children, termed "poly-victims," who have a very high
      burden of lifetime victimization. These children merit identification because
      they have high levels of psychological distress, some of the most serious
      victimization profiles, and a presumed vulnerability for further victimization.

PMID- 19589598
TI  - School functioning of children in residential care: the contributions of
      multilevel correlates.
AB  - OBJECTIVE: This study, using an ecological approach, examines the relationships
      between problems in school functioning (including academic and behavior problems)
      of children in residential care with a number of variables describing the child
      and the care setting. METHODS: The study reports on 4,061 children and youth
      (ages 6-20) in 54 Israeli residential care facilities supervised by the Ministry
      of Welfare. It is based on data derived from an ongoing system of monitoring care
      based on annual reports by social workers on children in care settings.
      Additionally, data on the characteristics of the settings were collected through
      a structured questionnaire completed by the supervisors at the Ministry of
      Welfare. Hierarchical Linear Modeling (HLM) was utilized to examine how
      characteristics of the individual children and the care settings were related to
      problems in school functioning among the children. RESULTS: Most of the children
      (about 62%) had at least one problem in school functioning. The most vulnerable
      children were boys, children who were taken from parental homes by court decree,
      children with problems in quality of contact with their biological parents, and
      children who stayed in the care setting for shorter periods. The settings'
      characteristics most associated with poor performance at school are group
      structure (vs. mixed and family home structures), higher levels of peer violence,
      fewer after-school activities, and settings in which children tend to stay for
      shorter periods of times. CONCLUSIONS: The findings demonstrate the need for an
      ecological perspective in addressing children's problems in school functioning
      within the care system. The results help to identify the types of placements that
      should benefit from additional resources in order to promote adaptive performance
      in school among the children. PRACTICE IMPLICATIONS: Social workers in
      residential care should give high priority to children's positive academic
      involvement. The study demonstrates the need for identifying the intersection of
      the individual, familial and institutional contexts in which problems in school
      functioning are more prevalent. Therefore, it is important to allocate sufficient
      resources to care settings which serve these children. The study suggests some
      priorities and directions for policy and practice with children in residential
      care.

PMID- 19589597
TI  - Experiences of psychological and physical aggression in adolescent romantic
      relationships: links to psychological distress.
AB  - OBJECTIVE: This research examined links between adolescents' experiences of
      psychological and physical relationship aggression and their psychological
      distress. Experiences of psychological and physical aggression were expected to
      correlate positively with symptoms of psychological distress, but experiences of
      psychological aggression were expected to partially account for the association
      between experiences of physical aggression and psychological distress. In
      addition, psychological aggression was hypothesized to be perceived as more
      unpleasant and less playful than physical aggression. METHOD: Participants were
      125 high school students. Relationship aggression was assessed over an 8-week
      period using two methods: (1) a retrospective method based on a single assessment
      at the end of the 8-week period, and (2) a cumulative method based on multiple
      assessments conducted during the 8-week period. Adolescents' appraisals of the
      aggression were also measured, as were their reports of symptoms of psychological
      distress. RESULTS: Adolescents' experiences of psychological and physical
      relationship aggression correlated positively, but inconsistently, with their
      symptoms of psychological distress. In analyses considering both forms of
      aggression simultaneously, psychological aggression was related to adolescents'
      distress, but physical aggression was not. This finding emerged across both
      methods of assessing for relationship aggression. Psychological aggression was
      more likely than physical aggression to be rated as unpleasant, and less likely
      to be attributed to the partner "playing around." CONCLUSIONS: The study of
      adolescent relationship aggression will benefit by expanding the focus of
      aggression to include psychological aggression as well as physical aggression,
      and by examining adolescents' appraisals of the aggression they experience.
      PRACTICE IMPLICATIONS: The findings highlight the importance of a broad view of
      aggression in adolescent relationships. Psychological aggression appears to be at
      least as important to adolescent well-being as physical aggression in dating
      relationships. In addition, it may be useful to consider how adolescents'
      interpret the intent of the aggression that they experience.

PMID- 19589599
TI  - Single and joint effects of Zn and Cd on Porcellio scaber (Crustacea, Isopoda)
      exposed to artificially contaminated food.
AB  - This study aimed at determining effects of Zn, Cd and their equitoxic mixtures on
      metal assimilation and food consumption of the terrestrial isopod Porcellio
      scaber, in relation to metal availability in the food. Cd was four times less
      water-extractable than Zn. Cd or Zn extractability was affected neither by metal
      concentration nor by the presence of the other metal. In single metal exposures,
      assimilation efficiency (AE) was up to five times higher for Cd than for Zn. In a
      mixture, AE of Cd significantly increased at low mixture concentrations and
      decreased at high mixture concentrations. AE of Zn significantly increased at
      intermediate mixture concentrations. Effects of the Zn and Cd mixture on food
      consumption were additive (28-day EC(50,total)=1.10TU; EC(50,water
      extractable)=1.18TU) when based on total and water-extractable concentrations but
      antagonistic when related to internal metal concentrations in the isopods
      (EC(50,internal)=1.40TU).

PMID- 19589600
TI  - Defining practice: flexibility, legitimacy, and the nature of systems of care and
      wraparound.
AB  - In human services, clear definition of key concepts and strategies is critical to
      facilitating training, implementation, and research. This article reflects on
      methods undertaken to specify the wraparound process for children and families,
      and considers lessons that may be relevant to defining the system of care
      concept.

PMID- 19589601
TI  - Formaldehyde in China: production, consumption, exposure levels, and health
      effects.
AB  - Formaldehyde, an economically important chemical, is classified as a human
      carcinogen that causes nasopharyngeal cancer and probably leukemia. As China is
      the largest producer and consumer of formaldehyde in the world, the Chinese
      population is potentially at increased risk for cancer and other associated
      health effects. In this paper we review formaldehyde production, consumption,
      exposure, and health effects in China. We collected and analyzed over 200 Chinese
      and English documents from scientific journals, selected newspapers, government
      publications, and websites pertaining to formaldehyde and its subsequent health
      effects. Over the last 20 years, China's formaldehyde industry has experienced
      unprecedented growth, and now produces and consumes one-third of the world's
      formaldehyde. More than 65% of the Chinese formaldehyde output is used to produce
      resins mainly found in wood products - the major source of indoor pollution in
      China. Although the Chinese government has issued a series of standards to
      regulate formaldehyde exposure, concentrations in homes, office buildings,
      workshops, public places, and food often exceed the national standards. In
      addition, there have been numerous reports of formaldehyde-induced health
      problems, including poisoning and cancer. The lack of quality epidemiological
      studies and basic data on exposed populations emphasizes the need for more
      extensive studies on formaldehyde and its related health effects in China.

PMID- 19589602
TI  - Antidepressants, social adversity and outcome of depression in general practice.
AB  - BACKGROUND: The role of current social risk factors in moderating the impact of
      antidepressant medication has not previously been explored. METHOD: In a RCT of
      SSRIs of general practice patients with mild to moderate depression (HDRS 12-19)
      two social indices of aversive experience were developed on the basis of prior
      research. First, the Life Events and Difficulties Schedule (LEDS) was used twice
      to document: i) recent stressful experience prior to baseline, and ii) after
      baseline and before follow up at 12 weeks both stressful and positive
      experiences, taking account of 'fresh start' and 'difficulty-reduction' events.
      Second, an index of unemployment-entrapment at baseline was developed for the
      current project. The HDRS was used to measure outcome as a continuous score and
      as a cut-point representing improvement below score 8. RESULTS: Each social index
      (LEDS and Unemployment-entrapment) was associated with a lower chance of
      remission at 12 weeks and each was required to model remission along with
      treatment arm. However there was no interaction: the degree of increased
      remission for those randomised to SSRIs plus supportive care compared to that for
      those with supportive care alone was the same regardless of social context.
      LIMITATIONS: Dating of remission was not as thorough as in previous work with the
      LEDS. Detailed examination of positive experiences suggested the large majority
      were not the result of remitting symptoms, but it is impossible to rule this out
      altogether. CONCLUSIONS: Remission rates among patients in aversive social
      contexts are consistently much lower irrespective of treatment. There is thus a
      need to evaluate the efficacy of alternative more socially focussed interventions
      for depressive conditions likely to take a chronic course in general practice.

PMID- 19589603
TI  - Rostral anterior cingulate cortex activity mediates the relationship between the
      depressive symptoms and the medial prefrontal cortex activity.
AB  - BACKGROUND: Depression is characterized by enhanced self-referential processing
      of negative emotional stimuli. Imaging studies have suggested that activation of
      both the medial prefrontal (MPFC) and anterior cingulate cortices (ACC) is
      associated with self-referential processing. However, whether this pattern of
      activation occurs in depressed individuals during the self-referential processing
      of the emotional stimuli had not been investigated to date. METHODS: Participants
      were 13 patients with major depressive disorder and 13 normal controls. We used
      block-designed functional magnetic resonance imaging (fMRI) to investigate neural
      activity during the self-referential judgments of positive and negative valenced
      personality trait words. RESULTS: Compared with the normal controls, the
      depressed patients showed hyperactivity in the MPFC and the rostral ACC during
      the self-referential processing of negative words. In addition, the activity of
      these regions during self-referential processing of the negative stimuli was
      correlated with the depressive symptom severity. The rostral ACC activity
      mediated the correlation between the MPFC activity and the depressive symptoms.
      Functional connectivity analysis revealed positive connectivities between the
      MPFC, the rostral ACC, and the amygdala. LIMITATION: Small N and antidepressant
      effect on imaging data limit the stability of reported findings. CONCLUSIONS: The
      relationships between the MPFC, the rostral ACC, and the amygdala appear to
      reflect an interaction between the self-referential processing and the negative
      emotional information processing, and we propose that the strong connection
      between the MPFC and the rostral ACC is associated with depressive symptoms.

PMID- 19589604
TI  - ICAM-5 modulates cytokine/chemokine production in the CNS during the course of
      herpes simplex virus type 1 infection.
AB  - Chemokines are important in HSE development in the CNS but underlying regulatory
      events are unknown. Two-hybrid binding assays identified that intercellular
      adhesion molecule 5 (ICAM-5), an immune modulator in the CNS, interacted with
      neurovirulence factor, UOL, of HSV-1. Viral load and interleukin levels were
      similar in UOL deletion virus (DeltaUOL), and wild type virus infected mouse
      brains. However, higher numbers of lymphocytes, but unaltered soluble ICAM-5 and
      chemokine levels were detected in DeltaUOL infected mouse brains. In contrast,
      lower lymphocyte numbers, reduced soluble ICAM-5, and higher chemokine levels
      were detected in wild type virus infected brains. Our results suggest that ICAM-5
      plays a critical role in modulating chemokine production in the CNS.

PMID- 19589605
TI  - Candidate biomarkers of chronic inflammatory demyelinating polyneuropathy (CIDP):
      proteome analysis of cerebrospinal fluid.
AB  - We aimed to identify disease-related biomarkers in CIDP. Using the two
      dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF from
      patients with CIDP (n = 11) and controls (n = 11). Protein spots that showed a
      significant difference were further analyzed by MALDI-TOF mass spectrometry. We
      identified 10 proteins that were upregulated in CIDP (two transferrin isoforms,
      alpha-1 acid glycoprotein 1 precursor, apolipoprotein A IV, two haptoglobin
      isoforms, transthyretin (TTR), retinol binding protein and two isoforms of
      proapolipoprotein) and 1 protein that was downregulated (integrin beta 8). The
      pathophysiological role of these proteins remains to be clarified by further
      studies.

PMID- 19589607
TI  - Polysomnography outcomes following transoral CO2 laser microsurgery in pediatric
      patients with laryngomalacia.
AB  - OBJECTIVE: Laryngomalacia is the most common cause of stridor in newborns and
      infants. The aim of the contribution was to present objectified data of the
      outcome of transoral CO(2) laser microsurgery in patients with laryngomalacia
      utilizing polysomnography (PSG). PATIENTS AND METHODS: This retrospective study
      comprised 21 patients who were diagnosed to suffer from laryngomalacia. Diagnosis
      was confirmed by pharyngo-laryngoscopy under spontaneous breathing. If there was
      evidence for laryngomalacia a transoral CO(2) lasersurgical intervention and/or
      epiglottopexy was performed in the same session. 8 patients, on whom the
      following should be focused, received pre- and postoperative PSG which was
      performed for efficiency control of the applied treatment. RESULTS: All 21
      patients underwent invasive treatment for laryngomalacia (lasersurgical division
      of the aryepiglottic folds: n=13; epiglottopexy: n=5; combined procedure: n=3).
      All patients were successfully extubated after surgery. In 20/21 cases breathing
      improved clearly after one single intervention. Stridor disappeared completely in
      the further course of the disease. In the 8 patients who received pre- and
      postinterventional PSG, lasersurgical interventions were performed. Statistical
      analysis of pre- and postoperative PSG revealed that MOAI/h (mixed obstructive
      apnea index/hour) improved significantly (p=0.016, Wilcoxon-Signed-Rank Test).
      Also desaturation/hour improved in the postoperative course (p=0.11). CONCLUSION:
      The presented concept describes an effective and reliable approach for
      diagnostics and treatment for laryngomalacia. To objectify the success of
      supraglottoplaty in patients suffering from severe laryngomalacia a pre- and
      postoperative PSG seems to be useful and advisable. The present results of PSG
      demonstrate that children with laryngomalacia to benefit from lasersurgical
      division of the aryepiglottic folds and/or epiglottopexy. This fact is supported
      by the postoperative improved clinical aspect.

PMID- 19589606
TI  - Oxygen radical production in leukocytes and disease severity in multiple
      sclerosis.
AB  - This study investigated the relationship between the formation of NADPH oxidase
      dependent oxygen radicals in peripheral blood leukocytes ('respiratory burst')
      and disease severity in patients with multiple sclerosis (MS). Oxygen radical
      production was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-Met-NH2
      (WKYMVM) or phorbol myristate acetate (PMA) and was assessed by quantifying
      superoxide anion, i.e. the initial radical formed by the NADPH oxidase. Disease
      severity was evaluated using the Multiple Sclerosis Severity Score (MSSS). In
      patients with severe disease, the production of superoxide anion was
      significantly lower for all three inducers of radical formation (p=0.04-0.004).
      Our findings are supportive of a protective role of oxygen radicals in
      autoimmunity.

PMID- 19589609
TI  - 2-Methoxyestradiol-induced radiosensitization is independent of SOD but depends
      on inhibition of Akt and DNA-PKcs activities.
AB  - BACKGROUND AND PURPOSE: 2-Methoxyestradiol (2-ME) is described as an inhibitor of
      the superoxide dismutase (SOD) enzyme activity. However, it attenuates PI3K/Akt
      pathway and induces radiosensitization in human tumor cells as well. Since the
      activation of catalytic subunit of DNA-protein kinase (DNA-PKcs) is partially
      regulated by Akt activity, in the present study we investigated whether 2-ME
      induced radiosensitization is dependent on inhibition of Akt and DNA-PKcs
      activities or on SOD targeting. MATERIALS AND METHODS: This study was performed
      using the lung carcinoma cell line A549. Ionizing radiation-induced SOD activity
      was analyzed by superoxide dismutase activity assay. Applying Western blotting,
      the pattern of radiation-induced SOD expression and activation of Akt as well as
      DNA-PKcs was analyzed. Colony formation assay and gammaH2AX foci assay were
      performed to measure radiosensitization and DNA-double strand break (DNA-DSB)
      repair. To downregulate SOD expression small interfering RNA (siRNA) was used.
      RESULTS: Irradiation with 4Gy stimulated SOD enzyme activity as early as 1min
      after radiation exposure. Expression of Cu/Zn-SOD (SOD1) as well as Mn-SOD (SOD2)
      was increased by single doses of 1-4Gy within 24-36h. 2-ME blocked radiation
      induced SOD enzyme activity but not protein expression and enhanced radiation
      sensitivity. Pretreatment with 2-ME blocked IR-induced Akt as well as DNA-PKcs
      phosphorylation and impaired the repair of DNA-DSB. SiRNA targeting of SOD1 and
      SOD2 affected neither DNA-PKcs phosphorylation nor post-irradiation survival
      while inhibition of Akt by specific inhibitor abrogated 2-ME-induced
      radiosensitization. CONCLUSION: These results may indicate that 2-ME-induced
      radiosensitization is independent of SOD inhibition but mainly depends on
      inhibition of Akt and DNA-PKcs activities.

PMID- 19589608
TI  - Biogenerics: the hope and the hype.

PMID- 19589610
TI  - Protective effect of milk constituents and sublethal injuries limiting process
      effectiveness during PEF inactivation of Lb. rhamnosus.
AB  - The inactivation of Lb. rhamnosus by pulsed electric field treatment (PEF) was
      studied in different fractions of raw milk and Ringer solution in order to
      evaluate the protective effect of nutrient rich media in comparison to aqueous
      buffer solutions. Apart from monitoring of culturability, analysis of the
      physiological fitness of Lb. rhamnosus was conducted aiming to identify
      sublethally damaged cells. Therefore, flow cytometry and a selective medium
      plating technique were used and compared to each other. The goal of the study was
      to apply three different parameters describing the physiological fitness of the
      model organism Lb. rhamnosus after PEF treatment such as culturability, membrane
      permeability and metabolic activity depending on treatment media and parameters.
      A concentration dependent protective effect of the milk protein fraction could be
      shown and allocated to micellar casein as the major milk protein. Increasing the
      concentration of whey proteins up to 2% showed a similar impact on limiting the
      PEF inactivation of Lb. rhamnosus. The evaluation of physiological fitness of
      cells was based on a determination of structural and functional characteristics
      by rapid cellular staining using carboxyfluorescein diacetate and propidium
      iodide. This approach showed good accordance to the conventional selective medium
      plating technique for the enumeration of sublethally-injured bacteria but flow
      cytometry provided additional information for the characterisation of this
      fraction. The extent of occurrence of dead, sublethal and vital fractions of
      cells was found dependent on the PEF treatment parameters such as electrical
      field strength and energy input as well as the different milk fractions used as
      treatment media.

PMID- 19589611
TI  - Age-related impairment of quality of life after lung resection for non-small cell
      lung cancer.
AB  - BACKGROUND: Health-related quality of life (QOL) after resection of non-small
      cell lung cancer (NSCLC) is of primary interest to clinicians, secondary to
      clinical outcome. However, few studies have explored QOL following lung resection
      and, to our knowledge, no studies have specifically examined the QOL of elderly
      patients. METHODS: A total of 131 patients with NSCLC underwent surgical
      resection (lobectomy or bilobectomy) between January 1998 and December 2004 and
      were enrolled in our prospective study. The patients' QOL and clinical data were
      assessed prior to resection and for up to 24 months after surgery using the EORTC
      QLQ C-30 questionnaire and the lung-specific questionnaire, QLQ-LC13. Quality of
      life was then calculated and the QOL of patients younger than 70 years was
      compared with that of patients aged 70 years or older. RESULTS: The overall 5
      year survival rate was 47%, and the rate of complications did not differ
      significantly between the groups. Overall, most QOL indicators, including
      physical function (p<0.001), pain (p=0.025), and dyspnea (p<0.001) were
      significantly impaired after surgery and remained so for up to 24 months. Elderly
      patients survived for an average of 39 months, while younger patients survived
      for an average of 49 months (p=0.18). The QOL of younger patients returned to
      preoperative levels significantly faster than did the QOL of elderly patients.
      CONCLUSIONS: Elderly patients who underwent lung resection for NSCLC failed to
      make a complete recovery. They showed a decreased tendency to achieve the
      preoperative level of QOL compared to younger patients.

PMID- 19589612
TI  - Acquired resistance to gefitinib: the contribution of mechanisms other than the
      T790M, MET, and HGF status.
AB  - BACKGROUND: Some types of somatic mutation of the epidermal growth factor
      receptor (EGFR) gene in non-small cell lung cancer (NSCLC) are associated with a
      significant clinical response to a tyrosine kinase inhibitor (TKI). However, most
      of the patients with this type of sensitive mutations in their tumor show
      acquired resistance during the TKI treatment. METHODS: The mutations in exons 19
      21 of the EGFR gene were examined in both the pre-treatment and the post
      treatment gefitinib resistant tumors in 10 patients with lung adenocarcinoma.
      Eight patients were recurrent cases after surgery, and two patients were non
      surgical cases whose tumor specimens were obtained from the metastatic lymph node
      and endobronchially invading tumor. RESULTS: In 10 patients, 5 patients had a
      deletion in exon 19 and another 5 did L858R mutation in exon 21 of EGFR in
      gefitinib pre-treatment tumors. The mutation status did not change in the
      gefitinib-resistant tumors. In 7 of 10 patients, the gefitinib-resistant tumors
      had a secondary T790M mutation, which was not detected in the gefitinib pre
      treatment tumors. In one patient, only one of the 4 gefitinib-resistant tumors
      showed the T790M mutation. Neither other novel secondary mutations of EGFR nor
      the K-ras were observed in their gefitinib-resistant tumors. Neither MET gene
      amplification nor HGF were observed in their gefitinib-resistant tumors without
      T790M mutation. CONCLUSIONS: The T790M mutation in the EGFR is relatively common
      in the patients with acquired resistance to gefitinib. However, mechanisms other
      than T790M, MET, and HGF status are involved in resistance to gefitinib.

PMID- 19589614
TI  - Preliminary indications from atomic force microscopy of the presence of rapidly
      formed nanoscale films on aquifer material surfaces.
AB  - The objective of this study was to determine if there is a nanoscale surface film
      on aquifer-like materials exposed to deep groundwaters, as has previously been
      found on surfaces exposed to surface and soil waters. Such surface films will
      modify surface properties that are so important in determining the mobility of
      many groundwater pollutants. Muscovite mica was used because a) it is a good
      analogue for the main sorbing phases of many clastic aquifers and b) its cleavage
      planes are atomically flat allowing high resolution imaging. Freshly-cleaved
      muscovite plates were exposed to groundwater from a sandstone aquifer for 30 min,
      and surface properties (morphology, coverage, roughness and tip-substrate force
      interactions) were measured using atomic force microscopy (AFM). A patchy surface
      film of several nanometres in depth, incorporating larger separate particles, was
      found on the mica surface. This film was associated with significantly increased
      roughness values and AFM probe-sample interaction forces compared with pure water
      and inorganic (synthetic groundwater) solution controls. Although the results
      reported are preliminary in nature, if confirmed, such films are likely to affect
      sorption reactions, surface-facilitated redox interactions, non-aqueous phase
      liquid wetting angles, and colloid-pathogen-rock attachment, and will thus be of
      importance in understanding natural attenuation and migration of dissolved, non
      aqueous and particulate phases in groundwaters.

PMID- 19589613
TI  - A fast and convenient new technique to detect the therapeutic target, K-ras
      mutant, from peripheral blood in non-small cell lung cancer patients.
AB  - Activating mutation of the K-ras gene was one of the earliest discoveries of
      genetic alterations in lung cancer. Moreover, K-ras somatic mutations might be
      suggested for predicting resistance to molecular antibodies targeting the
      epidermal growth factor receptor (EGFR). However, activated K-ras mutant
      detection methods are limited to traditional techniques. The techniques are
      complicated and are used only in tissue samples, which are limited for clinical
      applications. In a previous study, we established a low-cost, convenient, and
      easy technique for detecting activated K-ras in a small number of circulating
      tumor cells by the colorimetric membrane array method (CLMA). However, the
      sensitivity still needs further improvement. The aim of this study is to develop
      a new platform with chemiluminescence as reporter and weighted values of target
      genes on the chip in order to achieve a more sensitive, easier to read, and more
      accurate platform-weighted chemiluminecent membrane array (WCHMA). In advance, we
      collected 209 peripheral blood samples of non-small cell lung cancer (NSCLC) from
      patients to evaluate clinical K-ras activation detection using Activating KRAS
      Detection Chip both conducted by CLMA and WCHMA. Results show 71 specimens with K
      ras mutation, of which 59 were identified as positive through CLMA and 66 were
      positive through WCHMA. After statistical analysis, the sensitivity of CLMA was
      found to be 83% and the specificity was 96%. On the other hand, the sensitivity
      of WCHMA increased to 93% and the specificity remained at 94%. Results of the
      detection limitation of peripheral blood on two platforms are: 3cancer
      cells/cm(3) blood using WCHMA, which is better than 5cancer cells/cm(3) blood
      using CLMA. Further analysis on the correlation between the test results and
      clinical pathological features shows that the mean score obtained using WCHMA is
      significantly correlated to TNM stage, tumor size, and metastasis.

PMID- 19589615
TI  - On the co-purification of 6-sulfo LacNAc(+) dendritic cells (slanDC) with NK
      cells enriched from human blood.
AB  - The ability of NK cells to directly recognize pathogens and be activated via Toll
      like receptors (TLR) is increasingly recognized. Nevertheless, controversial
      results on the NK cell ability to be directly activated by lipopolysaccharide
      (LPS), the ligand of TLR4, have been recently reported. To start elucidating the
      reasons explaining the contrasting observations of the literature, we focused on
      the potential role of currently used NK cell purification procedures to condition
      putative NK cell responsiveness to LPS. To do so, human NK cells were isolated by
      negative selection, using three different commercial kits, to be comparatively
      evaluated for the production of IFNgamma in response to ultra-pure LPS and/or IL
      2. Despite the lack of surface TLR4, we found that two out of the three NK cell
      enriched populations released IFNgamma (and one of the two, IL-12p70 as well) in
      response to the LPS plus IL-2 combination, whereas the last one did not. However,
      the two LPS plus IL-2-responsive NK cell populations were found variably
      contaminated with 6-sulfo LacNAc(+) dendritic cells (slanDC), demonstrated
      responsible for triggering, via the production of IL-12p70 in response to LPS,
      the release of IFNgamma by IL-2-stimulated NK cells. Accordingly, slanDC
      depletion completely abrogated the capacity to produce both IL-12p70 and IFNgamma
      in response to LPS plus IL-2 by slanDC-containing NK cells. Taken together, our
      data uncover that two commercially available kits, specifically designed to
      isolate NK cells by negative selection, also co-purify variable amounts of
      slanDC. The latter cells may dramatically affect the outcome of experiments
      carried on to evaluate NK cell responsiveness to TLR agonists such as LPS.

PMID- 19589616
TI  - Vgamma9+ gammadelta T cells in systemic sclerosis patients are numerically and
      functionally preserved and induce fibroblast apoptosis.
AB  - Vdelta1 expressing gammadelta T cells are oligoclonally expanded in systemic
      sclerosis (SSc) (scleroderma) and thought to play an immunopathogenic role,
      whereas that of Vgamma9+ gammadelta T cells is unclear. In studies of 16 patients
      and 16 healthy controls (HCs) we found that whereas the percent of Vdelta1+
      gammadelta T cells was significantly elevated among the peripheral blood T cells
      in patients without radiographic evidence of interstitial lung disease (n=7),
      Vgamma9+ T cells were equally and persistently represented irrespective of
      pulmonary disease or cyclophosphamide treatment, at levels similar to healthy
      controls. Furthermore, ex vivo triggering of patient Vgamma9+ T cells with
      isopentenyl pyrophosphate plus interleukin-2-induced dose-dependent expansion,
      secretion of tumor necrosis factor alpha, and contact-dependent apoptosis of co
      cultured fibroblasts similarly to Vgamma9+ T cells of controls. Fully functional
      Vgamma9+ T cells persisting in the peripheral blood of patients with progressive
      systemic sclerosis could potentially play an immunopathogenic role in vivo by
      secreting cytokines and inducing death of fibroblasts in a contact-dependent
      manner when activated by specific antigens.

PMID- 19589617
TI  - Impaired nuclear functions lead to increased senescence and inefficient
      differentiation in human myoblasts with a dominant p.R545C mutation in the LMNA
      gene.
AB  - We have studied myoblasts from a patient with a severe autosomal dominant Emery
      Dreifuss muscular dystrophy (AD-EDMD) caused by an arginine 545 to cystein point
      mutation (p.R545C) in the carboxy-terminal domain of the lamin A/C gene. This
      mutation has pleiotropic cellular effects on these myoblasts as demonstrated by
      nuclear structural defects, exhibiting lobulations which increase with cell
      passages in culture. The organization of both lamin A/C and its inner nuclear
      membrane partner emerin are altered, eventually showing a honeycomb pattern upon
      immunofluorescence microscopy. In addition, the distribution of histone H3
      trimethylated at lysine 27 and of phosphorylated RNA polymerase II, markers of
      inactive and active chromatin domains, respectively, are altered suggesting an
      impact on gene expression. Patient myoblasts also presented a high index of
      senescence in ex vivo culture. Moreover, our data show for the first time in an
      AD-EDMD context that the 20S core particle of the proteasome was inactivated.
      With cell passages, the 20S core protein progressively accumulated into discrete
      nuclear foci that largely colocalized with promyelocytic leukemia (PML) bodies
      while p21 accumulated throughout the nuclear compartment. Proteasome inactivation
      has been linked to normal cellular ageing. Our data indicate that it may also
      contribute to premature senescence in AD-EDMD patient myoblasts. Finally, when
      transferred to low-serum medium, patient myoblasts were deficient in ex vivo
      differentiation, as assessed by the absence of myotube formation and myogenin
      induction. Altogether, these data suggest that the LMNA mutation p.R545C impairs
      both proliferation and differentiation capacities of myoblasts as part of the
      pathogenesis of AD-EDMD.

PMID- 19589618
TI  - Leprosy and Kaposi sarcoma presenting as an immune reconstitution inflammatory
      syndrome in a patient with AIDS.
AB  - The simultaneous presence of infectious organisms within cutaneous lesions of
      Kaposi sarcoma in persons with AIDS has been demonstrated. We describe a patient
      with concurrent leprosy and Kaposi sarcoma presenting as an immune reconstitution
      inflammatory syndrome in the setting of AIDS.

PMID- 19589619
TI  - Impact of revising the National Nosocomial Infection Surveillance System
      definition for catheter-related bloodstream infection in ICU: reproducibility of
      the National Healthcare Safety Network case definition in an Australian cohort of
      infection control professionals.
AB  - BACKGROUND: Effective and comparable surveillance for central venous catheter
      related bloodstream infections (CLABSIs) in the intensive care unit requires a
      reproducible case definition that can be readily applied by infection control
      professionals. METHODS: Using a questionnaire containing clinical cases,
      reproducibility of the National Nosocomial Infection Surveillance System (NNIS)
      surveillance definition for CLABSI was assessed in an Australian cohort of
      infection control professionals participating in the Victorian Hospital Acquired
      Infection Surveillance System (VICNISS). The same questionnaire was then used to
      evaluate the reproducibility of the National Healthcare Safety Network (NHSN)
      surveillance definition for CLABSI. Target hospitals were defined as large
      metropolitan (1A) or other large hospitals (non-1A), according to the Victorian
      Department of Human Services. Questionnaire responses of Centers for Disease
      Control and Prevention NHSN surveillance experts were used as gold standard
      comparator. RESULTS: Eighteen of 21 eligible VICNISS centers participated in the
      survey. Overall concordance with the gold standard was 57.1%, and agreement was
      highest for 1A hospitals (60.6%). The proportion of congruently classified cases
      varied according to NNIS criteria: criterion 1 (recognized pathogen), 52.8%;
      criterion 2a (skin contaminant in 2 or more blood cultures), 83.3%; criterion 2b
      (skin contaminant in 1 blood culture and appropriate antimicrobial therapy
      instituted), 58.3%; non-CLABSI cases, 51.4%. When survey questions regarding
      identification of cases of CLABSI criterion 2b were removed (consistent with the
      current NHSN definition), overall percentage concordance increased to 62.5%
      (72.2% for 1A centers). CONCLUSION: Further educational interventions are
      required to improve the discrimination of primary and secondary causes of
      bloodstream infection in Victorian intensive care units. Although reproducibility
      of the CLABSI case definition is relatively poor, adoption of the revised NHSN
      definition for CLABSI is likely to improve the concordance of Victorian data with
      international centers.

PMID- 19589620
TI  - [Geriatrics in the emergency department: a solid option].

PMID- 19589622
TI  - [Personalised Medication Dosage Systems for treatment compliance in patients with
      hypertension and dyslipidaemia].

PMID- 19589621
TI  - [Comparison of psychological well-being among Dominican and Spanish elders].
AB  - INTRODUCTION: Well-being and its association with distinct factors have played a
      central role in the arena of psychogerontology research. Given the importance of
      this topic, the present study examined several factors that could influence well
      being among the elderly of two countries. MATERIAL AND METHODS: This cross
      cultural study was based on a survey of two samples of elderly people, one from
      the Dominican Republic (N=1,296) and another from Spain (N=476), sampled,
      respectively, by stratification and quota sampling. Analyses included descriptive
      statistics, correlations and a multivariate analysis of covariance. RESULTS:
      Overall, sociodemographic factors were found to affect well-being both in the
      univariate and multivariate analyses. Nevertheless, the effect sizes were, in
      general, rather low. These effects were basically due to main effects rather than
      interactions. Age was negatively related to well-being. Marriage was associated
      with the highest levels of some well-being dimensions. The highest educational
      levels were also associated with higher levels of some well-being dimensions. The
      largest effect was due to country, with Dominicans scoring lower on all well
      being dimensions, even after statistically controlling for other factors.
      CONCLUSIONS: A main conclusion of this study was that sociodemographic factors
      did not differentially affect the two countries, given the rather low interaction
      effects. However, systematic effects were found for sociodemographic factors,
      independently of country. These effects were analyzed in light of the distinction
      between subjective and psychological well-being, and the data failed to support
      the idea of a different profile of results on these two types of well-being
      dimensions. Finally, given the large effect of country on all well-being
      dimensions, the relative importance of several sociopolitical and cultural
      factors was analyzed.

PMID- 19589623
TI  - [Scenes of tobacco in film and television in Spain].

PMID- 19589624
TI  - Synthesis and vasodilatory activity of some amide derivatives of 6-(4
      carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone.
AB  - Synthesis and vasodilatory activity of some amide derivatives of 6-(4
      carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone are reported. An effect of
      substitution at 2-position of pyridazinone ring on vasodilatory potential has
      also been explored. The most active compound 6-[4-(2-oxo-2-pyrrolidin-1-yl
      ethoxy)phenyl]-2-(4-fluorophenyl)-4,5-dihydropyridazin-3(2H)-one (11) exhibited
      vasodilating activity in nanomolar range (IC(50)=0.051 microM).

PMID- 19589625
TI  - Synthesis, characterization, antiamoebic activity and toxicity of novel
      bisdioxazole derivatives.
AB  - Cyclization of benzene-1,4-dicarbaldehyde dioxime 1 with different aromatic
      aldehydes in inert atmosphere yielded the corresponding new bisdioxazoles 2-11.
      The structure of 2-11 was elucidated by spectral data. In vitro antiamoebic
      activity was performed against HM1:IMSS strain of Entamoeba histolytica. The
      results showed that the compounds 3 (IC(50)=1.22 microM), 4 (IC(50)=1.41 microM),
      7 (IC(50)=1.05 microM) and 10 (IC(50)=1.01 microM) exhibited better antiamoebic
      activity than the standard drug metronidazole (IC(50)=1.80 microM). The compounds
      3, 4, 7 and 10 were tested for toxicity by MTT assay on H9c2 cardiac myoblasts
      and the results showed that the compounds 3, 4, 7 and 10 offered remarkable
      viability of 96.2%, 83.5%, 82% and 89%, respectively at a concentration of 12.5
      microg/ml.

PMID- 19589626
TI  - Synthesis of new 4-isopropylthiazole hydrazide analogs and some derived clubbed
      triazole, oxadiazole ring systems--a novel class of potential antibacterial,
      antifungal and antitubercular agents.
AB  - In the present study a series of 4-isopropylthiazole-2-carbohydrazide analogs,
      derived clubbed oxadiazole-thiazole and triazole-thiazole derivatives have been
      synthesized and characterized by IR, (1)H NMR, (13)C NMR, elemental and mass
      spectral analyses. The synthesized compounds were evaluated for their preliminary
      in vitro antibacterial, antifungal and antitubercular activity against
      Mycobacterium tuberculosis H(37)Rv strain by broth dilution assay method. The
      synthesized compounds 7a, 7b, 7d and 4 showed an antitubercular efficacy
      considerably greater than that of the parent 4-isopropyl-1,3-thiazole-2
      carbohydrazide 1, suggesting that the substituted 4-isopropylthiazole-2
      carbohydrazide moiety plays an important role in enhancing the antitubercular
      properties of this class of compounds. Compounds 2c, 3, 4, 6d, 7a and 7b
      exhibited good or moderate antibacterial and antifungal activity. Compounds 4 and
      7b showed appreciable cytotoxicity at a concentration of 250muM.

PMID- 19589627
TI  - [Splenic marginal zone lymphoma and autoimmunity: report of six cases].
AB  - INTRODUCTION: Autoimmune manifestations are common in splenic marginal zone
      lymphoma (SMZL) and are sometimes the presenting feature of the disease.
      Autoimmune cytopenia (anemia, thrombocytopenia) are the most frequently reported
      autoimmune conditions. However, other immunological manifestations may be
      associated with SMZL. METHODS: We report a retrospective case series of six
      patients with SMZL associated with autoimmunity. RESULTS: Auto-immune
      manifestations were the presenting feature of lymphoma in four cases. Auto-immune
      manifestations included auto-immune cytopenia in three cases (two hemolytic
      anemia and one pancytopenia), thyroiditis in two cases, systemic lupus and
      Still's disease in one case each. Antinuclear antibodies were detected with a
      titre of 1/250 in three cases, and with a titre of 1/32,000 in the patient with
      systemic lupus. Testing for DNA antibodies was negative in all cases. Two
      patients had a circulating lupus anticoagulant, with portal venous thrombosis
      following splenectomy in one case. One patient had hypogammaglobulinemia. A
      monoclonal gammopathy was detected in three patients. All patients had spleen
      enlargement. Immunophenotyping of blood peripheral lymphocyte was typical in five
      out of the six cases. Bone marrow was infiltrated in five out of the six cases.
      Diagnosis was obtained by the combination of immunophenotyping and bone marrow
      histopathology in five cases, and by splenic histopathology in the remaining
      case. Hepatitis C virus serology was negative in all patient. CONCLUSION:
      Autoimmune disease as systemic lupus or Still's disease may be associated with
      SMZL before its tumoral manifestations are evident. In this mode of presentation,
      spleen enlargement, hypogammaglobulinemia, monoclonal gammopathy, and multiple
      autoimmune diseases, should alert the physician.

PMID- 19589628
TI  - Administration of Chlorella sp. microalgae reduces endotoxemia, intestinal
      oxidative stress and bacterial translocation in experimental biliary obstruction.
AB  - RATIONALE: Endotoxemia has long been documented in obstructive jaundice, and
      altered intestinal barrier function is considered to be one of the important
      mechanisms for this phenomenon. The aim of this study was to investigate the role
      of different microalgae (Chlorella sp. and Spirulina sp.) extracts in intestinal
      barrier function and oxidative stress in experimentally jaundiced rats. METHODS:
      A total of 60 male wistar rats were randomly divided into four groups of 15 each:
      I, sham operated; II, bile duct ligation (BDL); III, BDL+Chlorella sp.; IV,
      BDL+Spirulina sp. Rats were fed rat chow or microalgae extracts supplemented
      enteral diet ten days after sham operation or BDL. Main outcome measures were
      endotoxin concentrations in plasma, evidence of bacterial translocation (BT) in
      mesenteric lymph nodes (MLNs) and liver, oxidative stress, and histology.
      RESULTS: Compared to the group I, a significant increase in contamined MLNs,
      liver, and spleen samples and increased endotoxemia were noted in group II
      (P<0.01) but were significant reduced in group III (P<0.05). There was no
      significant difference in BT rate between the group II and group IV (P>0.05).
      Moreover, Chlorella sp. administration protected in jaundiced rats against
      oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation,
      increase of the antioxidant reduced glutathione (GSH), and decrease of the
      oxidized glutathione (GSSG). The intestinal mucosa in control rats was atrophic
      with significantly decreased villous density and total mucosal thickness.
      Chlorella sp. caused a significant reduction in villous atrophy compared with
      controls. CONCLUSIONS: Chlorella sp. microalgae supplemented enteral diet has
      significant protective effects on intestinal mucosa barrier in obstructive
      jaundice, and reduces intestinal translocation of bacteria and endotoxin.

PMID- 19589629
TI  - Protection of the environment from ionising radiation in a regulatory context
      (protect): proposed numerical benchmark values.
AB  - Criteria are needed to be able to judge the level of risk associated with dose
      rates estimated for non-human biota. In this paper, European guidance on the
      derivation of predicted no-effect chemical concentrations has been applied to
      appropriate radiation sensitivity data. A species sensitivity distribution fitted
      to the data for all species resulted in a generic predicted no-effect dose rate
      of 10 microGy h(-1).Currently, data are inadequate to derive screening values for
      separate organism groups. A second, higher, benchmark could aid in decision
      making by putting results into context on the scale of no effect to a risk of
      'serious' effect. The need for, meaning and use of such a value needs to be
      debated by the wider community. This paper explores potential approaches of
      deriving scientific input to this debate. The concepts proposed in this paper are
      broadly consistent with the framework for human protection.

PMID- 19589630
TI  - Maternal decision on obtaining prenatal care: a study in Brazil.
AB  - OBJECTIVE: to address the social aspects of pregnancy and the views of pregnant
      women regarding prenatal assistance in Brazil. DESIGN: this qualitative study was
      focused on describing the Social Representations of prenatal care held by
      pregnant women. The discourse of the collective subject (DCS) framework was used
      to analyse the data collected, within the theoretical background of social
      representations, as proposed and developed by Serge Moscovici. PARTICIPANTS AND
      SETTING: 21 pregnant women who were users of the publicly funded Brazilian
      unified health-care system and resided in the area served by its family health
      programme in a low- to middle-income neighbourhood on the outskirts of Campo
      Grande, the capital of the state of Mato Grosso do Sul, in southwestern Brazil.
      Data were collected by conducting in-depth, face-to-face interviews from January
      to October 2006. FINDINGS: all participants were married. Formal education of the
      participants was less than five years in four cases, between five and eight years
      in six cases, and greater than 11 years in 10 cases. Nine participants had
      informal jobs and earned up to US$ 200 per month, four participants had
      administrative jobs and earned over US$ 500 per month, and eight participants did
      not work. No specific racial/ethnic background predominated. Lack of adherence to
      prenatal care allowed for the identification of two DCS themes: 'organisation of
      prenatal care services' and 'lifestyle features'. KEY CONCLUSIONS: the
      respondents were found to have negative feelings about pregnancy which manifest
      as many fears, including the fear of harming their children's health, of being
      punished during labour, and of being reprimanded by health-care professionals for
      overlooking their prenatal care, in addition to the insecurity felt towards the
      infant and self. IMPLICATIONS FOR PRACTICE: the findings reveal that
      communication between pregnant women and health-care professionals has been
      ineffective and that prenatal care has not been effective for the group
      interviewed--features that are likely to be found among other low- to middle
      income groups living elsewhere in Brazil.

PMID- 19589631
TI  - Work-related stress and work ability among Croatian university hospital midwives.
AB  - OBJECTIVE: to explore the sources and levels of stress at work and work ability
      among Croatian midwives. BACKGROUND: midwives are subjected to multiple
      stressors. Among health-care professionals, psychological distress for a
      prolonged period of time has negative effects on the worker's health, work
      ability and quality of patient care. 'Work ability' is a term describing a
      worker's resources related to physical, mental and social demands at work. As a
      measure of work ability in midwifery, the Work Ability Index (WAI) is considered
      to be a very predictive instrument; midwives with a poor WAI score usually leave
      their current job within five years. SETTING: university hospitals in Zagreb,
      Croatia. DESIGN: cross-sectional design survey. PARTICIPANTS: 300 health-care
      workers (105 qualified midwives and 195 paediatric nurses) were invited to
      complete the questionnaire. The total response rate was 53% (158/300). The sample
      included 14.7% of all hospital-based midwives in Zagreb hospitals. METHODS: the
      Occupational Stress Assessment Questionnaire (OSAQ) for health-care workers and
      the WAI questionnaire. FINDINGS: over three-quarters of the midwives (46/60,
      76.7%) believed that their job was stressful, and considered that insufficient
      work resources caused the most stress. More than half of the midwives associated
      an insufficient number of coworkers, unexpected situations, inadequate income,
      night work, incurable patients and poor organisation at work with a high level of
      stress. The perceived specific stressors differed between midwives and paediatric
      nurses in the same hospital. Insufficient work resources and poor organisation at
      work were more common stressors among midwives than paediatric nurses (p<0.05).
      Midwives and nurses differed significantly with respect to age (p=0.002).
      Midwives were younger and had spent fewer years working in their current
      workplace compared with paediatric nurses (p<0.001). Also, midwives had a lower
      level of education than paediatric nurses (p=0.044). The mean WAI score for
      midwives was 40.0 [95% confidence interval (CI) 38.4-41.4], compared with 37.5
      (95% CI 36.4-38.8) for paediatric nurses, both indicating good work ability.
      After adjusting for age, the difference in WAI score between the groups of
      workers was not significant. CONCLUSIONS: Croatian midwives experienced work
      related stress due to: insufficient work resources, insufficient number of
      coworkers, poor organisation at work, communication with superiors and emotional
      work. Midwives' work ability in relation to the demands of their job was good.
      These results confirmed that the WAI score decreases significantly with age.
      IMPLICATIONS FOR PRACTICE: hospital management needs to improve organisational
      factors and resources, as well as midwives' education and position in the health
      care system.

PMID- 19589632
TI  - Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes
      in the water quality of Salado River basin (Santa Fe, Argentina).
AB  - This field study assessed water quality of Salado River basin by using a set of
      biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured,
      including morphological indexes (condition factor, liver somatic index),
      hematological (red and white blood cells) and biochemical (glucose, total protein
      and cholinesterase activity) parameters. Besides, detoxication and oxidative
      stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver,
      gills and kidney. Despite water quality assessment did not show marked
      differences among sites, biomarkers responses indicate that fish are living under
      stressful environmental conditions. According to multivariate analysis glucose,
      glutathione S-transferase activity, lipid peroxidation levels and the count of
      white blood cells are key biomarkers to contribute to discrimination of sites.
      So, we suggest use those biomarkers in future monitoring of freshwater aquatic
      systems.

PMID- 19589633
TI  - Gender differences in education effects on all-cause mortality for white and
      black adults in the United States.
AB  - The existence of education differentials in adult mortality has been well
      established. The issue of gender differences in the education-mortality
      association, however, remains an open question, despite its importance for
      understanding of causal pathways through which education affects health outcomes.
      The goal of this paper is to analyze gender differences in education gradients in
      mortality among non-Hispanic white and black U.S. adults born between 1906 and
      1965. The analysis is based on data from the 1986-2000 National Health Interview
      Surveys linked to the National Death Index through 2002 (NHIS-LMF) with over
      700,000 respondents. Full-sample and cohort-stratified Cox proportional hazard
      models of all-cause mortality were estimated. Results indicate a great deal of
      similarity between men and women in the education-mortality association, with
      some exceptions. The most notable difference is the steeper educational gradient
      at high schooling levels for white men compared to white women. This difference
      was fully explained by marital status. No systematic gender differences in the
      relationship between education and adult mortality were observed among black
      adults in any birth cohorts. The findings suggest that men do not benefit from
      educational attainment uniformly more than women.

PMID- 19589634
TI  - Improving the effect of NaOCl pretreatment on bonding to caries-affected dentin
      using self-etch adhesives.
AB  - OBJECTIVE: To evaluate the effect of sodium hypochlorite pretreatment on adhesion
      to normal and caries-affected dentin using self-etch adhesives. METHODS: Forty
      extracted human molars with coronal carious lesions were used in this experiment.
      The occlusal dentin surfaces including the caries-affected dentin in each group
      were treated as follows: group 1, rinsed with water; group 2, treated with 6%
      NaOCl for 15s; group 3, treated with 6% NaOCl for 30 s; group 4, application with
      Accel for 30 s after NaOCl-30 s pretreatment. After rinsing with water and air
      drying, the treated dentin surfaces were applied with self-etch systems (Bond
      Force and Clearfil Protect Bond) according to the manufacturers' instructions,
      and built-up with resin composite. After 37 degrees C water storage for 24 h, the
      bonded normal or caries-affected dentin areas were isolated to create an
      hourglass configuration with a cross-sectional area of approximately 1 mm(2). The
      specimens were subjected to tensile stress at a cross-head speed of 1.0 mm/min.
      RESULTS: NaOCl-15 s pretreatment significantly improved the muTBS of both self
      etch adhesives to caries-affected dentin, while the 30 s pretreatment did not
      affect them. For normal dentin, NaOCl-30 s pretreatment significantly reduced the
      muTBS of both self-etch adhesives although the 15s pretreatment did not alter
      them. Furthermore, the application of Accel with a reducing effect increased the
      muTBS to normal and caries-affected dentin treated with NaOCl for 30 s.
      CONCLUSIONS: The effects of NaOCl pretreatment on bonding of both self-etch
      adhesives were dependent upon type of dentin (normal and caries-affected dentin)
      and the treatment time.

PMID- 19589635
TI  - The need for abdominal-only CPR during the resuscitation of infants suffering
      cardiac arrest following cardiac surgery.

PMID- 19589636
TI  - A molecular dynamics model of the Bt toxin Cyt1A and its validation by resonance
      energy transfer.
AB  - Cyt1A is a cytolytic toxin from Bacillus thuringiensis var. israelensis. A
      computer model of the toxin in solution was generated and validated by resonance
      energy transfer (RET). The average distance between the two tryptophans (residues
      158 and 161) and the fluorescently labeled cysteine 190 was 2.16 nm, which
      closely matched the distance predicted in computer simulations, 2.2 nm. The
      simulation results were able to explain two previous experimental observations:
      (i) amino-acid sequences of all Cyt toxins contain four blocks of highly
      conserved residues; and (ii) several single-point mutations drastically abrogated
      Cyt1A's toxicity. Selective randomization of atomic coordinates in the computer
      model revealed that the conserved blocks are important for proper folding and
      stability of the toxin molecule. Replacing lysine 225 with alanine, a mutation
      that renders the toxin inactive, was shown to result in breaking the hydrogen
      bonds between K225 and V126, L123, and Y189. Calculated Helmholtz free energy
      difference of the inactive mutation K225A was higher by 12 kcal/mol and 5
      kcal/mol than the values for the benign mutations K118A and K198A, respectively,
      which indicates that the K225A mutant is significantly destabilized. The normal
      mode and principal-component analyses revealed that in the wild-type Cyt1A the
      region around the residue K225 is quite stationary, due to the hydrogen-bond
      network around K225. In contrast, pronounced twisting and stretching were
      observed in the mutant K225A, and the region around the residue K225 becomes
      unstable. Our results indicate that conformational differences in this mutant
      spread far away from the site of the mutation, suggesting that the mutant is
      inactivated due to an overall change in conformation and diminished stability
      rather than due to a localized alteration of a "binding" or "active" site.

PMID- 19589637
TI  - Removal of Pb(II) ions from aqueous solution using activated tea waste:
      Adsorption on a fixed-bed column.
AB  - An inexpensive and effective adsorbent was developed from waste tea leaves for
      the dynamic uptake of Pb(II). Characterization of the adsorbents showed a clear
      change between physico-chemical properties of activated tea waste and simply tea
      waste. The purpose of this work was to evaluate the potential of activated tea
      waste in continuous flow removal of Pb(II) ions from synthetic aqueous effluents.
      The performance of the system was evaluated to assess the effect of various
      process variables, viz., of bed height, hydraulic loading rate and initial feed
      concentration on breakthrough time and adsorption capacity. The shape of the
      breakthrough curves was determined for the adsorption of Pb(II) by varying
      different operating parameters like hydraulic loading rate (2.3-9.17m(3)/hm(2)),
      bed height (0.3-0.5m) and feed concentration (2-10mg/l). An attempt has also been
      made to model the data generated from column studies using the empirical
      relationship based on the Bohart-Adams model. There was an acceptable degree of
      agreement between the data for breakthrough time calculated from the Bohart-Adams
      model and the present experimental study with average absolute deviation of less
      than 5.0%. The activated tea waste in this study showed very good promise as
      compared with the other adsorbents available in the literature. The adsorbent
      could be suitable for repeated use (for more than four cycles) without noticeable
      loss of capacity.

PMID- 19589638
TI  - Application of depression criteria (DSM-IV) in patients with Parkinson's disease.
AB  - INTRODUCTION: The aim of this study is to analyze the clinical differences
      between Parkinson's disease patients with major (MD) and minor depression (md)
      and to see how both affect the quality of life. MATERIAL AND METHODS: 118
      patients diagnosed with Parkinson's disease. The mean age of onset was 60.4+/
      11.2 years with a mean duration of 8.5+/-6.2 years. Depression was diagnosed
      according to DSM-IV-TR criteria. Scores on the Hamilton depression inventory,
      MMSE, PDQ-39, NPI-10, UPDRS III, and UPDRS IV were recorded. RESULTS: Twenty-one
      patients (17.8%) met the criteria of major depression (MD) and 33 (28.0%) those
      of minor depression (md). The scores on the PDQ-39 and NPI-10 of patients with MD
      were higher than in patients with md, and control group. The MMSE scores were
      lower in patients with MD. In 52.2% of the patients with MD, the diagnosis of
      depression was made prior to that of PD, this occurred only in 24.2% of the
      patients with md (p<0.001). The presence of anhedonia was related to cognitive
      impairment and the presence of neuropsychiatric symptoms. DISCUSSION: MD is
      probably a part of the disease process of PD; it is associated with cognitive
      impairment and may precede motor symptoms.

PMID- 19589640
TI  - Removal of Cr(VI) from polluted solutions by electrocoagulation: Modeling of
      experimental results using artificial neural network.
AB  - In the present work, the removal of Cr(VI) from synthetic and real wastewater
      using electrocoagulation (EC) process was studied. The influence of anode
      material, initial Cr(VI) concentration, initial pH of solution, type of
      electrolyte, current density and time of electrolysis was investigated. During 30
      min of electrocoagulation, maximum removal efficiencies achieved by Al and Fe
      anodes were 0.15 and 0.98, respectively. High removal efficiency was achieved
      over pH range of 5-8. NaCl, Na(2)SO(4) and NaNO(3) were used as supporting
      electrolyte during the electrolysis. NaCl was more effective than Na(2)SO(4) and
      NaNO(3) in removal of hexavalent chromium. Also in this work, a real
      electroplating wastewater containing 17.1mg/l Cr(VI) was treated successfully
      using EC process. Artificial neural network (ANN) was utilized for modeling of
      experimental results. The model was developed using a 3-layer feed forward
      backpropagation network with 4, 10 and 1 neurons in first, second and third
      layers, respectively. A comparison between the model results and experimental
      data gave high correlation coefficient (R(2)=0.976) shows that the model is able
      to predict the concentration of residual Cr(VI) in the solution.

PMID- 19589639
TI  - Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS
      mediated anti-cancer activity in human prostate cancer cells.
AB  - Prostate cancer, the most frequently diagnosed malignancy in elderly males of the
      United States, has become a major health issue in Asia. Previous studies have
      demonstrated that leaf extracts of Toona sinensis Roem. contain cytotoxic
      activity on several cancer cells including prostate cancer cells. In this study,
      gallic acid is identified as the major anti-cancer compound in T. sinensis leaf
      extracts. It is cytotoxic to DU145 prostate cancer cells, through generation of
      reactive oxygen species (ROS) and mitochondria-mediated apoptosis, which were
      reversed by antioxidants catalase and N-acetylcysteine. Furthermore, gallic acid
      is shown to block the growth of DU145 cells at G2/M phases by activating Chk1 and
      Chk2 and inhibiting Cdc25C and Cdc2 activities. In addition, gallic acid has a
      synergistic effect with doxorubicin in suppressing the growth of DU145 cells.
      Taken together, our results suggest that gallic acid has the potential to be
      developed into an anti-prostate cancer drug and is worthy of further studies.

PMID- 19589641
TI  - Adsorption of As(V) from water using Mg-Fe-based hydrotalcite (FeHT).
AB  - This paper describes a study of the sorptive removal of arsenate (As(V)) from
      aqueous solutions by synthetically prepared Mg-Fe-based hydrotalcites (FeHT) as
      layered double hydroxide (LDH) adsorbents. The synthesis of Fe(3+)-substituted
      hydrotalcites (FeHT) with the chemical formula
      [Mg(II)(6)Fe(III)(2)(OH)(16)](2+)[CO(3)xyH(2)O](2-) was achieved by a co
      precipitation method. The reaction products were characterized by powder X-ray
      diffraction analysis. The influences of solution pH, initial arsenate (As(V))
      concentration, and sorbent concentration were investigated in multiple kinetic
      runs. The adsorption rates and isotherms were investigated in batch experiments.
      The pseudo-first-order and second-order kinetic models were tested and the latter
      was found to fit better to the experimental data. Langmuir and Freundlich
      isotherms were used to describe the adsorption data from equilibrium experiments.
      The results have shown that FeHT has a high arsenate removal efficiency, with the
      ability to reduce the concentration of arsenate in the aqueous solution from an
      initial value of 330 microg/l to <10 microg/l (i.e. below the limit value
      specified by WHO).

PMID- 19589642
TI  - O(3) and O(3)/H(2)O(2) treatment of sulfonamide and macrolide antibiotics in
      wastewater.
AB  - The ubiquitous presence of trace pharmaceutical compounds in the environment is a
      significant concern. While the implications of these compounds on ecosystems and
      human health are being determined, there has been increasing interest in their
      treatment such as by tertiary processes at sources and wastewater treatment
      facilities to arrest further release to the environment. We have examined the
      degradation of sulfonamide and macrolide antibiotics in a spiked water and a
      pharmaceutical wastewater by ozonation under varied conditions such as
      concentration, contact time, pH, and H(2)O(2)/O(3) mole ratio. The results show
      faster removal kinetics for sulfonamides containing the aromatic ring than for
      macrolides built of mostly saturated hydrocarbon structure, and that complete
      removal of all is achieved within 20 min of ozonation at the application rate of
      0.17 g O(3)/min. Degradation of contaminants containing unsaturated C-C bonds
      occurs faster at low pH, consistent with O(3) being the predominant oxidant and
      its aqueous concentration being higher at low pH. Degradation of erythromycin
      having a fully saturated structure is slower and more effective at higher pH or
      with added H(2)O(2), both consistent with the enhanced production of OH radical
      under such conditions that contributes to removal of the saturated compound. Low
      pH favors degradation via molecular O(3) while high pH via OH radical; the
      optimal pH thus depends on target compounds being treated, and buffered pH at 7
      facilitates removal of all tested compounds. The addition of H(2)O(2) to
      ozonation abets contaminant removal, and at mole ratio of H(2)O(2)/O(3)=5 it
      attains the highest degradation speed for all contaminants. However, a large
      excess of added H(2)O(2) results in reduced or no benefits relative to O(3)
      alone. Thus, only a small dose of H(2)O(2) is desirable when widely disparate
      compounds are treated by ozonation.

PMID- 19589644
TI  - Is 'bipolar disorder' the brain's autopoietic response to schizophrenia?
AB  - Evidence is accumulating that schizophrenia and bipolar disorder are related
      conditions. This paper proposes a particular form of relatedness. If
      'schizophrenia' is a mind/brain 'trapped' between waking and dreaming, in a
      disordered in-between state, then bipolar 'disorder' could actually be an attempt
      to restore order. The mind/brain is a self-producing, self-organizing system.
      Autopoiesis applies to such systems. Neuromodulation accomplishes self
      organization in the mind/brain. If schizophrenia is a state in-between waking and
      dreaming, characterized by aminergic/cholinergic interpenetration and
      dopaminergic imbalance then bipolar 'disorder' could be a modulatory response.
      This autopoietic reaction may take the form of either aminergic hyperactivity
      aimed at producing a purer waking state, (precipitating mania in the waking
      state), or cholinergic hyperactivity aimed at producing a purer dreaming state,
      (producing depression in the waking state), or both, resulting in rapid cycling
      bipolar disorder. Thus bipolar activity may be an autopoietic response aimed at
      restoring differentiation to the in-between state of schizophrenia.

PMID- 19589645
TI  - Intraoperative field flooding with warm humidified CO2 may help to prevent
      adhesion formation after open surgery.
AB  - Postoperative adhesion formation is a common, serious, and costly complication,
      which may cause organ dysfunction, difficult re-operations, and chronic pain. The
      formation of adhesions after open surgery is partly due to the perioperative
      exposure of the wound cavity to ambient air, which initiates various local
      processes that cause inflammation and cellular damage in mesothelial layers.
      These adhesiogenic processes include superficial desiccation, airborne bacterial
      contamination and subsequent wound infection, and exposure to atmospheric oxygen
      with ensuing hyperoxia and oxidative stress. Here, we describe how recent results
      from experimental surgical research imply that the adverse effects of air
      exposure during open surgery could be prevented by the use of intraoperative
      field flooding with warm and humidified carbon dioxide. If proven effective in a
      clinical trial, a decreased incidence of postsurgical adhesions would thus save a
      lot of suffering, time, and money for the patients and the healthcare system.

PMID- 19589646
TI  - A radially expanding sheath for urethral dilation.
AB  - Urethral trauma caused by urethral dilation often leads to complications
      including gross hemorrhage and inflammation. The injury of the urethral mucosa
      is, in a large part, due to the shearing forces imposed on it during the
      introduction of dilation devices. In this article, a radially expanding sheath
      for urethral dilation is hypothesized by the authors. This device aims to reduce
      the axial forces during the insertion of dilators, thereby protecting the
      urethral mucosa from friction. When performing the endoscopy, the device could
      act as a barrier between urethral mucosa and the endoscope. Moreover, in the
      situation of encountering difficulties in catheterization, the sheath could also
      be used as a guide-wire to lead the catheter through its lumen course. Thus, it
      is proposed that this radially expanding sheath could be a potential powerful
      approach for reducing the risks and complications of urethral dilation.

PMID- 19589643
TI  - Methamphetamine facilitates female sexual behavior and enhances neuronal
      activation in the medial amygdala and ventromedial nucleus of the hypothalamus.
AB  - Methamphetamine (MA) abuse has reached epidemic proportions in the United States.
      Users of MA report dramatic increases in sexual drive that have been associated
      with increased engagement in risky sexual behavior leading to higher rates of
      sexually transmitted diseases and unplanned pregnancies. The ability of MA to
      enhance sexual drive in females is enigmatic since related psychostimulants like
      amphetamine and cocaine appear not to affect sexual drive in women, and in
      rodents models, amphetamine has been reported to be inhibitory to female sexual
      behavior. Examination of MA's effects on female sexual behavior in an animal
      model is lacking. Here, using a rodent model, we have demonstrated that MA
      enhanced female sexual behavior. MA (5mg/kg) or saline vehicle was administered
      once daily for 3 days to adult ovariectomized rats primed with ovarian steroids.
      MA treatment significantly increased the number of proceptive events and the
      lordosis response compared to hormonally primed, saline controls. The effect of
      MA on the neural circuitry underlying the motivation for sexual behavior was
      examined using Fos immunoreactivity. In the medial amygdala and the ventromedial
      nucleus of the hypothalamus, nuclei implicated in motivated behaviors, ovarian
      hormones and MA independently enhance the neuronal activation, but more striking
      was the significantly greater activation induced by their combined
      administration. Increases in dopamine neurotransmission may underlie the
      MA/hormone mediated increase in neuronal activation. In support of this
      possibility, ovarian hormones significantly increased tyrosine hydroxylase (the
      rate limiting enzyme in dopamine synthesis) immunoreactivity in the medial
      amygdala. Thus our present data suggest that the interactions of MA and ovarian
      hormones leads to changes in the neural substrate of key nuclei involved in
      mediating female sexual behaviors, and these changes may underlie MA's ability to
      enhance these behaviors.

PMID- 19589647
TI  - [Linguistic adaptation of the endometriosis health profile 5: EHP 5].
AB  - OBJECTIVES: The aim of this work was to develop a French version of an English
      quality of life questionnaire specific of endometriosis: endometriosis health
      profile 5. MATERIALS AND METHODS: After many translations and reverse
      translations, we got a first French version of EHP 5. This scale was then
      distributed in two centres: Poissy and Versailles. This questionnaire was
      completed by women with endometriosis proven and chronic pain. We studied
      acceptability and feasibility. RESULTS: Eighteen patients were included. All
      items have been completed satisfactorily. Our version was described as
      understandable and easy to complete. CONCLUSION: Our work consisted in developing
      a French version of EHP 5 which was very well received by the patient. However,
      the psychometric and clinical validation remains to be done.

PMID- 19589648
TI  - [Medical andragogy].

PMID- 19589650
TI  - Phylogenetic analysis and characterization of Korean bovine viral diarrhea
      viruses.
AB  - Thirty-six bovine viral disease viruses (BVDVs) were identified in bovine feces
      (n=16), brains (n=2), and aborted fetuses (n=18) in Korea. To reveal the genetic
      diversity and characteristics of these Korean strains, the sequences of their 5'
      untranslated regions (5'-UTRs) were determined and then compared with published
      reference sequences. Neighbor-joining phylogenetic analysis revealed that most of
      the Korean viruses were of the BVDV subtypes 1a (n=17) or 2a (n=17). The
      remaining strains were of subtypes 1b (n=1) and 1n (n=1). This analysis indicates
      that the 1a and 2a BVDV subtypes are predominant and widespread in Korea. In
      addition, the prevalence of BVDV-2 was markedly higher in aborted fetuses than in
      other samples and was more often associated with reproductive problems and
      significant mortality in cattle.

PMID- 19589649
TI  - Expression by Lawsonia intracellularis of type III secretion system components
      during infection.
AB  - Contact-dependent secretion systems, such as the type III secretion system
      (T3SS), have been shown to play significant roles in the pathogenicity of many
      gram-negative bacterial pathogens. Lawsonia intracellularis is a novel, obligate
      intracellular gram-negative bacterium, which has been identified as the
      etiological agent of proliferative enteropathies in numerous animal species.
      Analysis of the genome sequence of the L. intracellularis strain PHE/MN1-00 has
      revealed the presence of a T3SS secretion system in this bacterium. In this study
      we aimed to determine whether this important virulence mechanism is also present
      in L. intracellularis strain LR189/5/83. Using a PCR-based approach, we verified
      the presence of a genomic region encoding a T3SS. Specifically, a gene highly
      homologous to the yscN energiser component of the prototypic T3SS of Yersinia
      spp. was identified and termed lscN. Two further open reading frames (ORFs)
      contiguous with lscN were also identified: lscO and lscQ, which are also
      homologues of ORFs within the T3SS of Yersinia spp. To establish whether this
      T3SS may be functional, expression was monitored directly by RT-PCR and
      indirectly by detection of serological responses in vaccinated and infected
      animals. Transcripts for lscN and lscQ were detected and purified rLscQ was
      recognized by antiserum from infected pigs, indicating expression in vivo during
      infection. By analogy to other bacteria, this T3SS may be crucial for
      intracellular development and is likely to play a significant role in the
      virulence of this unusual pathogen.

PMID- 19589651
TI  - Neuropathogenic and non-neuropathogenic genotypes of Equid Herpesvirus type 1 in
      Argentina.
AB  - Infection with Equid Herpesvirus type 1 (EHV-1) leads to respiratory disease,
      abortion, and neurological disorders in horses. Molecular epidemiology studies
      have demonstrated that a single nucleotide polymorphism (A(2254)/G(2254)) in the
      genome region of the open reading frame 30 (ORF30), which results in an amino
      acid variation (N(752)/D(752)) of the EHV-1 DNA polymerase, is significantly
      associated with the neuropathogenic potential of naturally occurring strains. In
      order to estimate the prevalence of the EHV-1 neuropathogenic genotype in our
      country, we analyzed the ORF30 genome region of Argentinean EHV-1 isolates. The
      study was carried out by real time allelic discrimination PCR in 90 equine EHV-1
      positive samples, being 89 from 54 cases of abortion outbreaks (two of which were
      in association with neurological disease) and one from the respiratory tract of a
      healthy horse in training. Our results indicate that 7% (4/54) of the abortion
      outbreaks studied were induced by the neuropathogenic (G(2254)) genotype of EHV-1
      and 50% (2/4) of them were associated with simultaneous neurological disease.
      This information emphasizes the necessity to extreme the hygienic and preventive
      measures to diminish EHV-1 infections and consequently reduce the risk of
      epizootic neurological disease as has been recently observed in other countries.

PMID- 19589652
TI  - Spice: a never ending story?
AB  - On January 22nd 2009, the German Health Authorities prohibited several non
      traditional cannabinoids, that proved to be the active components in popular "Bio
      Designer-Drugs" like "Spice" and analogous products. The recent detection of CP
      47,497-C8 in Europe and Japan documents that these products have already spread
      world wide. We synthesized several potentially interesting alkylaminoindoles
      (alkylchain C(3) to C(7)) and isolated CP 47,497-C8 from "Spice Gold". The
      compounds were purified and characterized by NMR and mass spectrometry methods.
      With the aid of these authentic references we were able to detect and quantify
      added psychoactive compounds in different herbal blends. All samples that were
      acquired before the prohibition in December 2008 contained either CP 47,497-C8
      (5.4-11.0mg/g) or JWH-018 (2.3mg/g). Some samples acquired in March 2009, 4 weeks
      after the prohibition took place, still contained CP 47,497-C8 (3.0-3.3mg/g) but
      JWH-018 was not detected anymore. Instead it was replaced by its non-regulated
      C(4)-homolog JWH-073 (5.8-22.9 mg/g). Furthermore some of the new products did
      not contain any non-traditional cannabinoids. To our knowledge this is the first
      report of the appearance JWH-073 as a new designer drug. The data and method
      presented here will facilitate and accelerate the detection of these compounds in
      complex matrices.

PMID- 19589653
TI  - Effect of heat stress and bezafibrate on mitochondrial beta-oxidation: comparison
      between cultured cells from normal and mitochondrial fatty acid oxidation
      disorder children using in vitro probe acylcarnitine profiling assay.
AB  - Hyperpyrexia occasionally triggers acute life-threatening encephalopathy-like
      illnesses, including influenza-associated encephalopathy (IAE) in childhood, and
      can be responsible for impaired fatty acid beta-oxidation (FAO). In this regard,
      patients with impaired FAO may be more susceptible to febrile episodes. The
      effects of heat stress and a hypolipidemic drug, bezafibrate, on mitochondrial
      FAO were investigated using cultured cells from children with FAO disorders and
      from normal controls, using an in vitro probe acylcarnitine (AC) profiling assay.
      Fibroblasts were incubated in medium loaded with unlabelled palmitic acid for 96
      h at 37 and 41 degrees C, with or without bezafibrate. AC profiles in culture
      medium were analyzed by electrospray ionization tandem mass spectrometry. Heat
      stress, introduced by 41 degrees C, significantly increased acetylcarnitine (C2)
      but slightly decreased the other acylcarnitines (ACs) in controls and medium
      chain acyl-CoA dehydrogenase (MCAD)-deficient cells. On the other hand, in very
      long-chain acyl-CoA dehydrogenase (VLCAD)-deficient cells, accumulation of long
      chain ACs were enhanced at 41 degrees C, compared with that at 37 degrees C. In
      contrast, bezafibrate decreased long-chain ACs with significant increase of C2 in
      both control and VLCAD-deficient cells at 37 degrees C. These data suggest that
      heat stress specifically inhibits long-chain FAO, whereas bezafibrate recovers
      the impaired FAO. Our approach is a simple and promising strategy to evaluate the
      effects of heat stress or therapeutic drugs on mitochondrial FAO.

PMID- 19589655
TI  - [Letter on the article: "Study on personality and psychiatric disorder in
      fibromyalgia"].

PMID- 19589654
TI  - Simultaneous determination of risperidone and 9-hydroxyrisperidone enantiomers in
      human blood plasma by liquid chromatography with electrochemical detection.
AB  - Risperidone is a commonly prescribed antipsychotic drug. An enantioselective HPLC
      method with electrochemical detection was developed and validated for
      simultaneous determination of plasma concentrations of risperidone and its active
      metabolites, 9-hydroxyrisperidone enantiomers. Following solid phase extraction
      of 1.0 mL blood plasma, a baseline separation of the analytes was achieved on an
      AGP (alpha1 acid glycoprotein) column using isocratic mobile phase consisting of
      methanol-phosphate buffer (pH 6.2; 0.1 M) (15:85, v/v). Total analysis run time
      was 11 min. For the detection of the analytes analytical cell potentials were set
      at 500, 650, 950, and 950 mV. The method linearity was attained in the range from
      1.0 to 100 ng/mL for risperidone and both 9-hydroxyrisperidone enantiomers. The
      limit of detection was 0.5 ng/mL for all three analytes. The method was precise
      and accurate and was successfully applied in a clinical study investigating the
      stereoselectivity of risperidone 9-hydroxylation.

PMID- 19589657
TI  - Shyness and face scanning in children.
AB  - Contrary to popular beliefs, a recent empirical study using eye tracking has
      shown that a non-clinical sample of socially anxious adults did not avoid the
      eyes during face scanning. Using eye-tracking measures, we sought to extend these
      findings by examining the relation between stable shyness and face scanning
      patterns in a non-clinical sample of 11-year-old children. We found that shyness
      was associated with longer dwell time to the eye region than the mouth,
      suggesting that some shy children were not avoiding the eyes. Shyness was also
      correlated with fewer first fixations to the nose, which is thought to reflect
      the typical global strategy of face processing. Present results replicate and
      extend recent work on social anxiety and face scanning in adults to shyness in
      children. These preliminary findings also provide support for the notion that
      some shy children may be hypersensitive to detecting social cues and intentions
      in others conveyed by the eyes. Theoretical and practical implications for
      understanding the social cognitive correlates and treatment of shyness are
      discussed.

PMID- 19589658
TI  - PER-1-type extended-spectrum beta-lactamase-producing Acinetobacter baumannii
      clinical isolates from India.

PMID- 19589659
TI  - Hydrazine-induced liver toxicity is enhanced by glutathione depletion but is not
      mediated by oxidative stress in HepG2 cells.

PMID- 19589660
TI  - Rhodococcus equi endocarditis in immunocompetent hosts: report of the first two
      cases.

PMID- 19589661
TI  - NMR dipolar constants of motion in liquid crystals: Jeener-Broekaert, double
      quantum coherence experiments and numerical calculation on a 10-spin cluster.
AB  - Two proton quasi-equilibrium states were previously observed in nematic liquid
      crystals, namely the S and W quasi-invariants. Even though the experimental
      evidence suggested that they originate in a partition of the spin dipolar energy
      into a strong and a weak part, respectively, from a theoretical viewpoint, the
      existence of an appropriate energy scale which allows such energy separation
      remains to be confirmed and a representation of the quasi-invariants is still to
      be given. We compare the dipolar NMR signals yielded both by the Jeener-Broekaert
      (JB) experiment as a function of the preparation time and the free evolution of
      the double quantum coherence (DQC) spectra excited from the S state, with
      numerical calculations carried out from first principles under different models
      for the dipolar quasi-invariants, in a 10-spin cluster which represents the 5CB
      (4(')-pentyl-4-biphenyl-carbonitrile) molecule. The calculated signals
      qualitatively agree with the experiments and the DQC spectra as a function of the
      single-quantum detection time are sensible enough to the different models to
      allow both to probe the physical nature of the initial dipolar-ordered state and
      to assign a subset of dipolar interactions to each constant of motion, which are
      compatible with the experiments. As a criterion for selecting a suitable quasi
      equilibrium model of the 5CB molecule, we impose on the time evolution operator
      consistency with the occurrence of two dipolar quasi-invariants, that is, the
      calculated spectra must be unaffected by truncation of non-secular terms of the
      weaker dipolar energy. We find that defining the S quasi-invariant as the subset
      of the dipolar interactions of each proton with its two nearest neighbours yields
      a realistic characterization of the dipolar constants of motion in 5CB. We
      conclude that the proton-spin system of the 5CB molecule admits a partition of
      the dipolar energy into a bilinear strong and a multiple-spin weak contributions
      therefore providing two orthogonal constants of motion, which can be prepared and
      observed by means of the JB experiment. This feature, which implies the existence
      of two timescales of very different nature in the proton-spin dynamics, is
      ultimately dictated by the topology of the spin distribution in the dipole
      network and can be expected in other liquid crystals. Knowledge of the nature of
      the dipolar quasi-invariants will be useful in studies of dipolar-order
      relaxation, decoherence and multiple quantum NMR experiments where the initial
      state is a dipolar-ordered one.

PMID- 19589662
TI  - Alpha-tocopherol-loaded Ca-pectinate microcapsules: optimization, in vitro
      release, and bioavailability.
AB  - We used response surface methodology to optimize microcapsule preparation
      conditions, including the ratio of pectin:alpha-tocopherol (TP) (X(1)),
      emulsifier concentration (X(2)), and CaCl(2) concentration (X(3)) for maximal
      entrapment efficiency (EE) of TP-loaded Ca-pectinate microcapsules. The values of
      X(1), X(2), and X(3), optimized for maximal EE were a ratio of 9.7:6.3, and 1.33%
      and 5.09%, respectively. The experimental results obtained from the optimum
      formulation agreed with the predicted results, indicating the usefulness of
      models for EE. TP release from the Ca-pectinate microcapsules prepared according
      to the optimized conditions was slow and incomplete in simulated gastric fluid,
      whereas it was relatively rapid and considerably sustained in simulated
      intestinal fluid. An in vivo release study revealed that physical entrapment of
      TP within Ca-pectinate microcapsules can be a good technique to demonstrate the
      sustained release pattern of TP and to improve the bioavailability for TP
      following oral administration.

PMID- 19589663
TI  - [Why teams in charge of children after a pediatric intensive care unit stay do
      not take into account the treatment limitation decisions previously made by
      intensivists].
AB  - The fact that some children may survive despite a limitation of treatment
      decision (LTD) made in the pediatric intensive care unit (PICU) is a recent
      concern. A previous study pointed out that the teams in charge of children after
      the PICU stay did not take previous PICU LTDs into account. PURPOSE: To identify
      the problems different units experience in cooperating with the PICU team, in
      order to increase the continuity of care for these children. STUDY DESIGN:
      Qualitative single-center study, using semi-structured interviews with physicians
      in charge of children who were discharged from the PICU even though a LTD was
      made. RESULTS: Nine pediatric subspecialists (hemato-oncologists, neurologists,
      and neurosurgeons) were interviewed, producing a corpus of approximately 80 pages
      of typed text. Three conflictual situations were identified by these physicians.
      The most frequently reported situation was being asked by the PICU team to give
      expert advice on a patient's prognosis, before a LTD was made. The 2 others had
      to defend a true care plan for children who were transferred to the PICU and
      designing a new care plan for children who were discharged from the PICU after a
      LTD was made. CONCLUSION: The medical reasoning model that is used for LTDs in
      the PICU generates conflictual situations when compared to the models that are
      used in other specialties. These models represent various expressions of
      subjectivity, as in any medical decision. Acknowledging this fact could
      facilitate its integration into clinical practice and should improve authentic
      debates that are necessary to ensure continuity of care for these children.

PMID- 19589665
TI  - Management of glioblastoma multiforme in HIV patients: a case series and review
      of published studies.
AB  - AIMS: HIV infection is associated with an increased incidence of glioblastoma
      multiforme (GBM). Here we report four new cases of HIV-associated GBM, discuss
      these in the context of previously reported cases, and consider aspects of
      current glioma management in HIV-positive patients. METHODS AND RESULTS: Twenty
      one cases of GBM in HIV-positive patients, including four treated recently at our
      own institution, are discussed. The median age at presentation of the whole
      series was 38 years (range 19-60 years). The median CD4 count at GBM presentation
      was 400 cells/mm(3) (range 80-610 cells/mm(3)). Patients had been HIV positive
      for a median of 3 years (range 0-11 years) before tumour presentation. Treatment
      and survival were analysed in 16 of the 21 patients (five published cases were
      excluded: three due to lack of further information and two spinal cord tumours).
      Treatment included surgical debulking, radical radiotherapy and chemotherapy, all
      of which were well tolerated. The median survival was 8 months for the 16
      patients with assessable data. CONCLUSIONS: GBM occurs at an increased frequency
      and younger age in the HIV population than in the general population. HIV itself
      is not found in glioma specimens, but the effect of HIV infection on reduced
      immune surveillance is thought to promote the development of these tumours. The
      approach to management of HIV-positive patients with GBM should be the same as
      the general population, using surgery, radiotherapy and chemotherapy. Vincristine
      should be used with caution due to potential interactions with highly active
      antiretroviral therapy, causing an increased rate of autonomic neuropathy.
      Continuous low-dose temozolomide treatment should also be used cautiously because
      of potential additive lymphopenia. Survival of glioma patients with HIV is
      dictated by their tumour, not their HIV status.

PMID- 19589664
TI  - Life cycle and molecular phylogeny of the dinoflagellates Chytriodinium and
      Dissodinium, ectoparasites of copepod eggs.
AB  - The dinoflagellates Chytriodinium affine, C. roseum and Dissodinium pseudolunula
      are ectoparasites of crustacean eggs. Here, we present new observations regarding
      their life cycle based on coastal plankton samples and incubations and analyze
      their molecular phylogeny using the small subunit ribosomal RNA gene (SSU rDNA)
      as a marker. In contrast to the typical stages already documented for its life
      cycle, we observed that D. pseudolunula dinospores may exceptionally
      differentiate inside a globular cyst. Despite its parasitic life style, the cysts
      and dinospores of D. pseudolunula contain chlorophyll a. We obtained the first
      SSU rDNA sequences for the genera Chytriodinium (the type C. roseum and C.
      affine) and Dissodinium (D. pseudolunula). Classical taxonomical schemes have
      ascribed these genera to the order Blastodiniales. However, our SSU rDNA-based
      phylogenetic analysis shows that these ectoparasites form a clade in the
      Gymnodinium sensu stricto group, unarmored dinokaryotic dinoflagellates of the
      order Gymnodiniales. They branch in a subgroup composed of warnowiids,
      polykrikoids, the type of Gymnodinium, G. fuscum and G. aureolum. Although
      Chytriodinium and Dissodinium appear to be relatives based on SSU rDNA phylogeny,
      feeding and host specificity, their life cycles are substantially different.
      Based on these data we consider that the type of life cycle is a poor criterion
      for classification at the family level. We suggest that the morphology of the
      infective cell is probably the most reliable phenotypic characteristic to
      determine the systematic position of parasitic dinoflagellates.

PMID- 19589666
TI  - A letter to the editor.

PMID- 19589667
TI  - Indigowood root extract protects hematopoietic cells, reduces tissue damage and
      modulates inflammatory cytokines after total-body irradiation: does Indirubin
      play a role in radioprotection?
AB  - Radix of Isatis indigotica (indigowood root, IR) has been used in traditional
      medicine for its potential anti-inflammatory effect. The purpose of this study is
      to investigate the radioprotective effects of radiation caused damages in
      hematopoietic system and normal tissues in mice. A total of 57 BALB/c mice were
      randomized into six treatment groups: control, IR treatment (0.195, 0.585 and
      1.170 g/kg, p.o. daily), L-glutamine (0.520 g/kg) and sham group. All mice except
      the sham group were irradiated and then administered for one week. The
      radioprotective effect on hematopoietic system, serum cytokines, and intestinal
      toxicity was studied. Protective effects on spleen and thymus are found in IR
      treated groups. IR assisted in restoration of leukocytopenia after whole mice
      irradiation with significant reduction of serum TNF-alpha, IL-1beta, and IL-6.
      These enhancements of hematopoietic effects are due to an increase in the serum G
      CSF concentration in IR treated groups. In histopathological assessment,
      significant improvement of intestine toxicity is observed in high-dose IR and L
      glutamine group. Evidences show that IR has potentials to be a radioprotector,
      especially in recovery of hematopoietic system, reduction of inflammatory
      cytokines and intestinal toxicity. Indirubin may play a crucial role, but the
      underlying mechanism is not very clear and warrants further studies.

PMID- 19589668
TI  - Early supported discharge schemes in older patients with an exacerbation of
      chronic obstructive pulmonary disease: a real life experience.

PMID- 19589669
TI  - Kinetics of scrap tyre pyrolysis under vacuum conditions.
AB  - Scrap tyre pyrolysis under vacuum is attractive because it allows easier product
      condensation and control of composition (gas, liquid and solid). With the aim of
      determining the effect of vacuum on the pyrolysis kinetics, a study has been
      carried out in thermobalance. Two data analysis methods have been used in the
      kinetic study: (i) the treatment of experimental data of weight loss and (ii) the
      deconvolution of DTG (differential thermogravimetry) curve. The former allows for
      distinguishing the pyrolysis of the three main components (volatile components,
      natural rubber and styrene-butadiene rubber) according to three successive steps.
      The latter method identifies the kinetics for the pyrolysis of individual
      components by means of DTG curve deconvolution. The effect of vacuum in the
      process is significant. The values of activation energy for the pyrolysis of
      individual components of easier devolatilization (volatiles and NR) are lower for
      pyrolysis under vacuum with a reduction of 12K in the reaction starting
      temperature. The kinetic constant at 503K for devolatilization of volatile
      additives at 0.25atm is 1.7 times higher than that at 1atm, and that
      corresponding to styrene-butadiene rubber at 723K is 2.8 times higher. Vacuum
      enhances the volatilization and internal diffusion of products in the pyrolysis
      process, which contributes to attenuating the secondary reactions of the
      repolymerization and carbonization of these products on the surface of the char
      (carbon black). The higher quality of carbon black is interesting for process
      viability. The large-scale implementation of this process in continuous mode
      requires a comparison to be made between the economic advantages of using a
      vacuum and the energy costs, which will be lower when the technologies used for
      pyrolysis require a lower ratio between reactor volume and scrap tyre flow rate.

PMID- 19589670
TI  - Furniture wood wastes: experimental property characterisation and burning tests.
AB  - Referring to the industrial wood waste category (as dominant in the provincial
      district of Pesaro-Urbino, Marche Region, Italy), this paper deals with the
      experimental characterisation and the carrying out of non-controlled burning
      tests (at lab- and pilot-scale) for selected "raw" and primarily "engineered"
      ("composite") wood wastes. The property characterisation has primarily revealed
      the following aspects: potential influence on moisture content of local weather
      conditions at outdoor wood waste storage sites; generally, higher ash contents in
      "engineered" wood wastes as compared with "raw" wood wastes; and relatively high
      energy content values of "engineered" wood wastes (ranging on the whole from 3675
      to 5105 kcal kg(-1) for HHV, and from 3304 to 4634 kcal kg(-1) for LHV). The
      smoke qualitative analysis of non-controlled lab-scale burning tests has
      primarily revealed: the presence of specific organic compounds indicative of
      incomplete wood combustion; the presence exclusively in "engineered" wood burning
      tests of pyrroles and amines, as well as the additional presence (as compared
      with "raw" wood burning) of further phenolic and containing nitrogen compounds;
      and the potential environmental impact of incomplete industrial wood burning on
      the photochemical smog phenomenon. Finally, non-controlled pilot-scale burning
      tests have primarily given the following findings: emission presence of carbon
      monoxide indicative of incomplete wood combustion; higher nitrogen oxide emission
      values detected in "engineered" wood burning tests as compared with "raw" wood
      burning test; and considerable generation of the respirable PM(1) fraction during
      incomplete industrial wood burning.

PMID- 19589671
TI  - Novel application of surface plasmon resonance biosensor chips for measurement of
      advanced glycation end products in serum of Zucker diabetic fatty rats.
AB  - Advanced glycation end products (AGEs) have been implicated in diabetic
      complications. To measure AGEs, especially N(epsilon)-(carboxymethyl)lysine
      (CML), in sera from Zucker diabetic fatty rats (ZDF) and Zucker lean rats (ZL),
      we used a novel method of protein chip and surface plasmon resonance imaging
      (SPRI). Serum samples were obtained from male ZDF and ZL rats at 20 weeks of age.
      Antibodies to AGEs or CML were immobilized on a gold surface, which was modified
      by cysteine-tagged, protein-G constructs. The gold chip upon which the serum was
      spotted was optically coupled with a prism coupler. The reflected images from the
      gold chip were obtained using a charge-coupled device (CCD) camera. The direct
      analysis of the glycated proteins and products using SPRI showed that AGEs and
      CML levels were elevated in ZDF serum, compared with ZL serum. The lowest
      detection limit of AGEs was 10 ng/ml, with a working range covering the
      physiological range. These results indicate that the protein chip and SPRI system
      is very suitable for the measurement of glycated proteins and end products in
      serum samples. This system offers high sensitivity without any fluorescent or
      other labeling of the components and saves a substantial amount of time,
      resources, and labor. Our results suggest that SPRI systems can be used as a tool
      to diagnose diabetic complications.

PMID- 19589672
TI  - Corn stover pretreatment by inorganic salts and its effects on hemicellulose and
      cellulose degradation.
AB  - Inorganic salts, NaCl, KCl, CaCl(2), MgCl(2), FeCl(2), FeSO(4), FeCl(3), and
      Fe(2)(SO(4))(3), were studied as catalysts for the degradation of hemicellulose
      in corn stover. FeCl(3) significantly increased the hemicellulose degradation in
      aqueous solutions heated between 140 and 200 degrees C with high xylose recovery
      and low cellulose removal, amounting to approximately 90% and <10%, respectively.
      Hemicellulose removal increased 11-fold when the corn stover was pretreated with
      0.1 M FeCl(3) compared to pretreatment with hot water under otherwise the same
      conditions, which was also 6-fold greater than pretreatment with dilute sulfuric
      acid at the same pH. Optimum pretreatment conditions were found where the corn
      stover was pretreated with 0.1 M FeCl(3) at 140 degrees C for 20 min. Under such
      conditions, 91% of hemicellulose was removed, and the recovery of monomeric and
      oligomeric xylose in liquid fraction achieved 89%, meanwhile, only 9% of
      cellulose was removed.

PMID- 19589673
TI  - Characteristics of rice husk gasification in an entrained flow reactor.
AB  - Experiments were performed in an entrained flow reactor to better understand the
      characteristics of biomass gasification. Rice husk was used in this study.
      Effects of the gasification temperature (700, 800, 900 and 1000 degrees C) and
      the equivalence ratio in the range of 0.22-0.34 on the biomass gasification and
      the axial gas distribution in the reactor were studied. The results showed that
      reactions of CnHm were less important in the gasification process except cracking
      reactions which occurred at higher temperature. In the oxidization zone,
      reactions between char and oxygen had a more prevailing role. The optimal
      gasification temperature of the rice husk could be above 900 degrees C, and the
      optimal value of ER was 0.25. The gasification process was finished in 1.42 s
      when the gasification temperature was above 800 degrees C. A first order kinetic
      model was developed for describing rice husk air gasification characteristics and
      the relevant kinetic parameters were determined.

PMID- 19589675
TI  - Comparison on the removal of phthalic acid diesters in a bioreactor landfill and
      a conventional landfill.
AB  - The removal of phthalic acid diesters (PAEs) in municipal solid waste (MSW) from
      two simulated landfill reactors was compared. The results showed that the
      original concentrations of dimethyl phthalate (DMP), dibutyl phthalate (DBP) and
      dioctyl phthalate (DOP) in the refuse were 3.3 microg g(-1), 18.5 microg g(-1)
      and 0.8 microg g(-1), respectively. The concentrations of DMP and DBP in both
      leachate and refuse decreased greatly during decomposition of the waste in both
      reactors. The major loss of PAEs from the landfill occurred during an active
      methanogenic environment with a low concentration of volatile fatty acids (VFA)
      in the later period. In addition, strong correlations were found between the
      residual DMP, DBP concentrations and the biologically degradable material (BDM)
      of the refuse. Finally, PAEs degraded more rapidly in the landfill that was
      operated in conjunction with the methanogenic reactor when compared to the
      landfill with direct leachate discharge.

PMID- 19589674
TI  - Biosorption of nonylphenol on dead biomass of Rhizopus arrhizus encapsulated in
      chitosan beads.
AB  - The nonylphenol (NP) biosorption and desorption potential for fungal biomass used
      under batch conditions was investigated using kinetics and isotherm models.
      Fungal biomass of Rhizopus arrhizus TISTR 3610 exhibited preferential uptake of
      NP, an endocrine disrupting chemicals. Sporangiospores, asexual spores, were
      immobilised in chitosan beads. The biosorption data of NP on the moist heat
      inactivated R. arrhizus-chitosan beads were analyzed using four popular
      adsorption isotherms and, by using non-linear least-regression with the solver
      add-in in Microsoft Excel, correlated in order with the Fritz-Schluender>Redlich
      Peterson>Freundlich>Langmuir isotherms. The pseudo first-order kinetics was found
      to have the best fit with the experimental data. The diffusivity of NP in the R.
      arrhizus-chitosan beads was calculated using the shrinking core model, and the
      diffusivity values were in the ranges of 2.3736x10(-4)-1.8950x10(-4) cm(2) s(-1).
      Desorption to recover the adsorbed NP from the beads was performed in methanol
      and was best described using a pseudo second-order kinetic model.

PMID- 19589676
TI  - Synthesis and structure-activity relationship of dicationic diaryl ethers as
      novel potent anti-MRSA and anti-VRE agents.
AB  - A series of dicationic diaryl ethers have been synthesized and evaluated for in
      vitro antibacterial activities, including drug resistant bacterial strains. Most
      of these compounds have shown potent antibacterial activities. Several compounds,
      such as piperidinyl and thiomorpholinyl compounds 9e and 9l, improved the
      antimicrobial selectivity and kept potent anti-MRSA and anti-VRE activity. The
      most potent bis-indole diphenyl ether 19 exhibited anti-MRSA MIC value of 0.06
      microg/mL and enhanced antimicrobial selectivity.

PMID- 19589677
TI  - Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK)
      inhibitors.
AB  - A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors.
      Extensive SAR studies supported by molecular modeling afforded a highly potent
      and selective compound 36. Compound 36 demonstrated good antitumor efficacy in
      xenograft nude rat model.

PMID- 19589678
TI  - Semi-synthesis and anti-proliferative activity evaluation of novel analogues of
      Honokiol.
AB  - A series of honokiol analogues were synthesized by modifying the 5- and/or 3'
      position(s) of honokiol to assess their anti-tumor effects. Some compounds
      exerted more potent anti-proliferative activities than those of honokiol on K562
      leukemia cells, A549 alveolar basal epithelial cells, SPC-A1 adenocarcinoma cells
      and A2780 human ovarian carcinoma cells in vitro. Compounds 2b, 3a, and 3c
      displayed most potent anti-proliferative activities against these tested cell
      strains and their anti-drug resistance effects were evaluated in vitro on
      cisplatin-resistant A2780 human ovarian carcinoma cells. The structure-activity
      relationship was also proposed.

PMID- 19589679
TI  - G-quadruplex structures: in vivo evidence and function.
AB  - Although many biochemical and structural studies have demonstrated that DNA
      sequences containing runs of adjacent guanines spontaneously fold into G
      quadruplex DNA structures in vitro, only recently has evidence started to
      accumulate for their presence and function in vivo. Genome-wide analyses have
      revealed that functional genomic regions from highly divergent organisms are
      enriched in DNA sequences with G-quadruplex-forming potential, suggesting that G
      quadruplexes could provide a nucleic-acid-based mechanism for regulating telomere
      maintenance, as well as transcription, replication and translation. Here, we
      review recent studies aimed at uncovering the in vivo presence and function of G
      quadruplexes in genomes and RNA, with a particular focus on telomeric G
      quadruplexes and how their formation and resolution is regulated to permit
      telomere synthesis.

PMID- 19589680
TI  - Comment on "rare anatomical variation of the C7 pedicle and the intra-spinal
      course of the C7 nerve root".

PMID- 19589681
TI  - A newly developed endoscopic sheath for the removal of large putaminal hematomas.
AB  - This report describes the removal of large putaminal hematomas using an
      endoscopic surgical technique with a 3 mL syringe barrel as a conduit. The 3 mL
      syringe barrel (outer diameter, 8mm) was used as an endoscopic sheath and a 14 F
      Foley catheter was modified as an endoscopic stylet. With the patient in the
      supine position, we used an entry point on the temporal scalp, ipsilateral to the
      hematoma. From January 2005 to January 2006, 25 patients with large putaminal
      hematomas underwent endoscopic surgery. The inclusion criteria for endoscopic
      surgery were: (i) putaminal hemorrhage with hematoma volume>40 mL; and (ii) a
      Glasgow Coma Scale (GCS) score of 3 to 12 with a focal neurological deficit. The
      exclusion criteria were: (i) a hemorrhage due to tumor, trauma, aneurysm, or
      arteriovenous malformation; (ii) non-putaminal hemorrhages; and (iii)
      coagulopathy. No surgical complications occurred. The time from the onset of
      symptoms to surgery ranged from 1 hour to 5 hours (median, 2 hours). Preoperative
      hematoma volumes ranged from 40 mL to 180 mL (median, 78 mL); postoperative
      hematoma volumes ranged from 2 mL to 16 mL (median, 6 mL). Therefore, 90 to 97%
      (median, 93%) of the hematoma was evacuated. The preoperative GCS scores ranged
      from 3 to 12 (median, 8); the postoperative GCS scores ranged from 6 to 15
      (median, 12). The mortality rate was 16%; one year postoperatively, the mean
      Glasgow Outcome Scale score was 2.7. Thus, endoscopic removal of large putaminal
      hematomas is safe, effective, and minimally invasive. The new endoscopic sheath
      is inexpensive, disposable, and easy to use.

PMID- 19589682
TI  - Effect of bone marrow stromal cell-conditioned medium on the glutamate uptake of
      peroxide-injured astrocytes.
AB  - We aimed to investigate the effect of bone marrow stromal cell-conditioned medium
      (BCM) on glutamate uptake of peroxide (H(2)O(2))-injured astrocytes. Bone marrow
      stromal cells (BMSC) were isolated from rat bone marrow. Confluent BMSC cultures
      were incubated with serum-free Dulbecco's Modified Eagle's Medium to create the
      BCM. Astrocytes were isolated from 1-day-old rats. H(2)O(2)-injured astrocytes
      were cultured in BCM (experimental group) or serum-free medium (control group).
      The labeled glutamate ((3)H-L-glutamate) uptake by H(2)O(2)-injured astrocytes
      with or without BCM was compared after 1 and 3 days. We found that astrocytes
      cultured in BCM exhibited increased glutamate uptake compared to those cultured
      in serum-free medium following H(2)O(2)-induced injury (p<0.01) and concluded
      that BCM increased the glutamate uptake capability of H(2)O(2)-injured rat
      astrocytes. The therapeutic benefits associated with BMSC transplantation
      following brain injury might be partly due to increased glutamate uptake by
      astrocytes.

PMID- 19589683
TI  - Predicting the longer term outcomes of total knee arthroplasty.
AB  - We asked the question of what are the patient level predictors (age, gender, body
      mass index, education, ethnicity, mental health, and comorbidity) for a sustained
      functional benefit at a minimum of 1 year follow-up after total knee
      arthroplasty(TKA). Five hundred fifty-one consecutive patients were reviewed from
      our joint registry between the years of 1998 and 2005. Baseline demographic data
      and the outcome scores of the Western Ontario McMaster University Osteoarthritis
      Index (WOMAC) and Medical Outcomes Short-Form 36 (SF36) scores were extracted
      from the database. Longitudinal regression modeling was performed to identify the
      predictive factors of interest. We had 27% of data points missing. The mean
      follow-up in our cohort was 3.0 years (range 1-8 years) and there were no
      revisions performed during this time. Clinical outcome scores were found to be
      relatively constant for 3-4 years after surgery and then demonstrated a gradual
      decline after that. Older age, year of follow-up, greater comorbidity, and a
      poorer mental health state at time of surgery were identified as negative
      prognostic factors for a sustained functional outcome following TKR (P<0.05).
      Knowledge of these factors that predict outcomes should be used in setting
      appropriate patient expectations of surgery.

PMID- 19589685
TI  - Quantitative evaluation of process induced strain in MOS transistors by
      Convergent Beam Electron Diffraction.
AB  - Convergent Beam Electron Diffraction (CBED) experiments and simulations
      associated with Finite Element calculations were performed in order to measure
      strain and stress in a complex device such as periodic MOS transistors with a
      spatial resolution of about 2 nm and a sensitivity that could reach 50 MPa. A
      lamella of a thickness of about 475 nm was extracted from the wafer with the
      transistors by Focus Ion Beam (FIB) and was observed in cross-section in a
      Transmission Electron Microscope (TEM). When approaching the transistors, the
      HOLZ lines of the CBED patterns acquired in the silicon substrate, become broader
      and broader. This HOLZ line broadening, which is due to the stress relaxation in
      the thin foil, was used to determine quantitatively the strain and stress in the
      lamella and then in the bulk device. We showed that this procedure could be
      applied to a complex device. Two parameters, the intrinsic material strains--or
      equivalently the intrinsic material stresses--in the nickel silicide (NiSi) and
      nitride (Si(3)N(4)) layers on the top of the transistors gate, were successfully
      fitted by trial and error, in the procedure.

PMID- 19589684
TI  - Syntheses and biological evaluations of carbosilane dendrimers uniformly
      functionalized with sialyl alpha(2-->3) lactose moieties as inhibitors for human
      influenza viruses.
AB  - A series of carbosilane dendrimers uniformly functionalized with sialyl lactose
      moieties (Neu5Ac alpha2-->3Gal beta1-->4Glc) was systematically synthesized, and
      biological evaluations for anti-influenza virus activity using the
      glycodendrimers were performed. The results suggested that the glycodendrimers
      had unique biological activities depending on the form of their core frame, and
      Dumbbell(1)6-amide type glycodendrimer 7 showed particularly strong inhibitory
      activities against human influenza viruses [A/PR/8/34 (H1N1) and A/Aichi/2/68
      (H3N2)]. The results suggested that the structure-activity relationship (SAR) on
      the glycolibrary against various influenza viruses was observed, and dumbbell
      shaped dendrimers as supporting carbohydrate moieties were found to be the most
      suitable core scaffolds in this study.

PMID- 19589686
TI  - Light-regulated Arabidopsis ACBP4 and ACBP5 encode cytosolic acyl-CoA-binding
      proteins that bind phosphatidylcholine and oleoyl-CoA ester.
AB  - In Arabidopsis thaliana, six genes encode acyl-CoA-binding proteins (ACBPs) that
      show conservation of an acyl-CoA-binding domain. These ACBPs display varying
      affinities for acyl-CoA esters, suggesting of different cellular roles. We have
      recently reported that three members (ACBP4, ACBP5 and ACBP6) are subcellularly
      localized to the cytosol by biochemical fractionation, confocal microscopy of
      transgenic Arabidopsis expressing autofluorescence-tagged fusions and immuno
      electron microscopy using ACBP-specific antibodies. In this study, we observed by
      Northern blot analysis that ACBP4 and ACBP5 mRNAs in rosettes were up-regulated
      by light and dampened-off in darkness, mimicking FAD7 which encodes omega-3-fatty
      acid desaturase, an enzyme involved in plastidial lipid metabolism. Results from
      in vitro binding assays indicate that recombinant ACBP4 and ACBP5 proteins bind
      [(14)C]oleoyl-CoA esters better than recombinant ACBP6, suggesting that light
      regulated ACBP4 and ACBP5 encode cytosolic ACBPs that are potential candidates
      for the intracellular transport of oleoyl-CoA ester exported from the chloroplast
      to the endoplasmic reticulum for the biosynthesis of non-plastidial membrane
      lipids. Nonetheless, His-tagged ACBP4 and ACBP5 resemble ACBP6 in their ability
      to bind phosphatidylcholine suggesting that all three ACBPs are available for the
      intracellular transfer of phosphatidylcholine.

PMID- 19589687
TI  - Anthocyanin production in callus cultures of Cleome rosea: modulation by culture
      conditions and characterization of pigments by means of HPLC-DAD/ESIMS.
AB  - Leaf and stem explants of Cleome rosea formed calluses when cultured on MS medium
      supplemented with different concentrations of 2,4-dichlorophenoxyacetic acid (2,4
      D) or 4-amino-3,5,6-trichloropicolinic acid (PIC). The highest biomass
      accumulation was obtained in the callus cultures initiated from stem explants on
      medium supplemented with 0.90 microM 2,4-D. Reddish-pink regions were observed on
      callus surface after 6-7 months in culture and these pigments were identified as
      anthocyanins. Anthocyanins production was enhanced by reducing temperature and
      increasing light irradiation. Pigmented calluses transferred to MS1/2 with a 1:4
      ratio NH(4)(+)/NO(3)(-), 70 g L(-1) sucrose and supplementation with 0.90 microM
      2,4-D maintained a high biomass accumulation and showed an increase of 150% on
      anthocyanin production as compared with the initial culture conditions.
      Qualitative analysis of calluses was performed by high performance liquid
      chromatography coupled to diode array detector and electrospray ionization mass
      spectrometry (HPLC-DAD/ESIMS). Eleven anthocyanins were characterized and the
      majority of them were identified as acylated cyanidins, although two peonidins
      were also detected. The major peak was composed by two anthocyanins, whose
      proposed identity were cyanidin 3-(p-coumaroyl) diglucoside-5-glucoside and
      cyanidin 3-(feruloyl) diglucoside-5-glucoside.

PMID- 19589688
TI  - Early secondary gingivo-alveolo-plasty in the treatment of unilateral cleft lip
      and palate patients: 20 years experience.
AB  - Since 1988, the Milano surgical protocol has included lip, nose and soft palate
      repair at 6-9 months of age and closure of the hard palate at 18-36 months
      together with an Early Secondary Gingivo-Alveolo-Plasty (ESGAP). Prior to 1988
      the alveolar cleft was repaired in a third step by bone grafting at 9-11 years of
      age. The goal of this study was to evaluate the long-term maxillary growth in
      unilateral cleft lip and palate (UCLP) patients who have undergone ESGAP.
      Alveolar ossification after ESGAP was also studied in the permanent dentition.
      Growth assessment was carried out comparing lateral X-ray cephalograms of a UCLP
      ESGAP sample (15 consecutive patients with a mean age of 18.2 +/-1.2 years) and
      of the UCLP bone graft sample (10 consecutive patients with a mean age of 18.7 +/
      1.1 years) and a sample from the Oslo cleft lip and palate (CLP) centre sample
      (15 patients with a mean age of 18.1 +/-0.8 years). Alveolar ossification in the
      sample which had undergone ESGAP was evaluated through a sample of panoramic X
      rays of UCLP in the permanent dentition. Alveolar bridging was assessed using a
      modified Bergland's scoring system. From the results it seems that ESGAP allows
      for an excellent alveolar ossification, but patients show an inhibition of
      maxillary growth compared with the secondary bone graft group and with the Oslo
      group. Although ESGAP allows for early repair of the alveolus together with
      palate repair, thus eliminating in all patients the need for secondary bone
      grafting, it seems to have an inhibiting influence on maxillary growth which
      increases the need for Le Fort I osteotomies. It is however fair to recall, that,
      even with an adjunctive Le Fort I osteotomy, ESGAP enables the total number of
      operations to be reduced to three, instead of most European protocols (4-5
      procedures).

PMID- 19589689
TI  - Destination therapy with a rotary blood pump and novel power delivery.
AB  - OBJECTIVE: We tested the hypothesis that a miniaturised axial flow pump with
      infection-resistant power delivery could improve longevity and quality of life
      (QOL) in advanced heart failure patients deemed unsuitable for transplantation.
      METHODS: The study included all non-United States Jarvik 2000 patients (n=46),
      where a skull-pedestal-based power line was employed with the intention of long
      term support. Patient age ranged from 29 to 80 years. Of the 46 patients, 42 were
      male. All were New York Heart Association (NYHA) IV predominantly with idiopathic
      dilated (n=22) or ischaemic (n=18) cardiomyopathy. The experience (2000-2008)
      included the learning curve of 10 centres. RESULTS: The internal components are
      imperceptible. The power/control system is user friendly, allowing excellent QOL.
      There has been no pump malfunction. The Kaplan-Meier survival analysis is shown.
      The longest event-free survival is 7.5 years. Support exceeded 3 years in five
      cases. The cumulative experience exceeds 50 years. Three patients were
      transplanted, and two pumps were replaced at 90 and 203 days. Nineteen cases are
      ongoing (mean: 663 days), while 22 died during support (mean survival: 402 days),
      of which five from non-device-related diseases. Temporary local infection
      occurred in three pedestals, and there has been no pump infection. Incidence of
      thrombo-embolic events showed wide variation between centres. CONCLUSIONS: From
      this learning-curve experience, both left ventricular assist device (LVAD) and
      power delivery are reliable and promising for destination therapy. Early
      mortality is similar to other studies and relates to the severity of illness.
      Pump infection has not occurred and prolonged event-free survival is clearly
      possible with expert medical management.

PMID- 19589690
TI  - Early results of bilateral pulmonary artery banding for hypoplastic left heart
      syndrome.
AB  - OBJECTIVE: To compare the haemodynamics and perioperative course of initial
      palliation with bilateral pulmonary artery banding (PAB) and the Norwood
      procedure. METHODS: Between April 2004 and December 2007, 43 consecutive children
      with hypoplastic left heart syndrome (HLHS) or a variant underwent initial
      palliation (PAB, n=18; Norwood, n=25). Clinical perioperative data were analysed.
      In the PAB group, lipo-prostaglandin E1 administration was continued with
      hospitalisation until stage 2 palliation with a bi-directional Glenn shunt and
      the Norwood procedure. RESULTS: There were no significant differences in the age
      and operative weight of patients who received stage 1 palliation (PAB, 12+/-9
      days, 2.7+/-0.6 kg; Norwood, 12+/-8 days, 2.8+/-0.4 kg). The PAB group had more
      high-risk patients than the Norwood group (PAB, 83%; Norwood, 48%, p=0.04).
      Increased early and inter-stage mortality were observed in patients who underwent
      the Norwood procedure (early mortality with PAB, 6% vs Norwood, 12%; inter-stage
      mortality, 6% vs 27%, respectively). Mortality between stages 1 and 2 was 11% for
      the PAB group and 36% for the Norwood group. The Kaplan-Meier survival estimate
      at 1 year did not differ between groups (77% for the PAB group, 64% for the
      Norwood group). Ductal stenosis was found in one patient in the PAB group during
      the follow-up period. Twenty-eight patients underwent stage 2 reconstruction, and
      the patients in the PAB group were younger at the time of surgery (PAB, 116 days;
      Norwood, 224 days). There were no significant differences between groups in
      pulmonary artery index regarding body surface area (BSA) (PAB, 179 mm(2)BSA(-1);
      Norwood, 194 mm(2)BSA(-1)) and the incidence of ventricular dysfunction after
      stage 2 construction (PAB, 21%; Norwood, 21%). CONCLUSIONS: Bilateral PAB with
      continuous lipo-prostaglandin E1 administration may improve early and
      intermediate mortality in infants with HLHS. Intimate care with hospitalisation
      may contribute to the results.

PMID- 19589691
TI  - Evaluation of a new chest tube removal protocol using digital air leak monitoring
      after lobectomy: a prospective randomised trial.
AB  - BACKGROUND: The objective of this randomised trial was to assess the
      effectiveness of a new fast-track chest tube removal protocol taking advantage of
      digital monitoring of air leak compared to a traditional protocol using visual
      and subjective assessment of air leak (bubbles). METHODS: One hundred and sixty
      six patients submitted to pulmonary lobectomy for lung cancer were randomised in
      two groups with different chest tube removal protocols: (1) in the new protocol,
      chest tube was removed based on digitally recorded measurements of air leak flow;
      (2) in the traditional protocol, the chest tube removal was based on an
      instantaneous assessment of air leak during daily rounds. The two groups were
      compared in terms of chest tube duration, hospital stay and costs. RESULTS: The
      two groups were well matched for several preoperative and operative variables.
      Compared to the traditional protocol, the new digital recording protocol showed
      mean reductions in chest tube duration (p=0.0007), hospital stay (p=0.007) of 0.9
      day, and a mean cost saving of euro 476 per patient (p=0.008). In the new chest
      tube removal protocol, 51% of patients had their chest tube removed by the second
      postoperative day versus only 12% of those in the traditional protocol.
      CONCLUSIONS: The application of a chest tube removal protocol using a digital
      drainage unit featuring a continuous recording of air leak was safe and cost
      effective. Although future studies are warranted to confirm these results in
      other settings, the use of this new protocol is now routinely applied in our
      practice.

PMID- 19589692
TI  - Is tricuspid valve replacement a catastrophic operation?
AB  - OBJECTIVE: Tricuspid valve replacement (TVR) has a high postoperative mortality,
      despite recent advances in perioperative care. We report the results of our
      experience in TVR with an emphasis on early mortality and morbidity and long-term
      follow-up. METHODS: Between October 1994 and August 2007, 80 consecutive TVRs
      were performed in 78 patients. The mean age was 48+/-14 (range: 20-70) years. The
      underlying disease of the patients was classified as rheumatic (n=54), congenital
      (n=12), endocarditis (n=10) or degenerative (n=4). Previous cardiac surgery had
      been performed in 40 patients (50%). Isolated TVR was performed in 24 patients
      (30%). RESULTS: Hospital mortality occurred in one patient (1.4%). Postoperative
      morbidities included intra-aortic balloon pump (n=5), bleeding re-operation
      (n=4), delayed sternal closure (n=3), acute renal failure (n=3), subdural
      haematoma (n=3), extracorporeal membrane oxygenation (n=1), mediastinitis (n=1)
      and pacemaker insertion (n=4). In 42 patients, ventilator support was needed for
      more than 72 h. Based on multivariate analysis, age (p<0.001) and the
      cardiopulmonary time (p=0.004) were the identified risk factors. Follow-up was
      completed in all patients with a mean duration of 56+/-37 (range: 0-158) months.
      During the follow-up period, there were seven deaths (8.8%), including five
      cardiac deaths. The 5- and 8-year survival rates were 95+/-3% and 79+/-9% and
      event-free survival rates were 76+/-6% and 61+/-9%, respectively. Based on
      multivariate analysis, the only identified predictors of late deaths was a
      postoperative low cardiac output (p=0.024). CONCLUSIONS: TVR can be performed and
      low operative mortality can be achieved thorough optimal perioperative management
      in the current era.

PMID- 19589693
TI  - Hybrid treatment for aortic arch and proximal descending thoracic aneurysm:
      experience with stent grafting for second-stage elephant trunk repair.
AB  - BACKGROUND: Aortic aneurysm affecting the arch and proximal descending thoracic
      aorta may require a two-stage repair, which includes proximal elephant trunk
      graft placement and completion of descending thoracic aortic repair. The
      combination of open surgery and endovascular grafting may improve the morbidity
      and mortality of the patient population at risk. METHODS: Between February 2001
      and March 2007, 258 patients underwent thoracic aortic endovascular grafting at
      our institution, wherein 31 patients underwent a hybrid approach involving
      proximal arch repair and elephant trunk graft replacement, and endovascular
      completion procedures. All patients, who underwent combined endovascular and open
      procedures in the management of the aortic arch and proximal descending thoracic
      aortic aneurysms, were reviewed and analysed retrospectively. RESULTS: The
      interval between the first and second stage ranged from 0 to 14 months with a
      mean interval of 3.1 months. Follow-up ranged from 0 to 70 months with a mean of
      31 months. Technical success was achieved in all patients. The 1, 12, 36 and 60
      month mortality rates were 6.4%, 16.5%, 26.7% and 26.7%, respectively. Caudal
      migration of the endograft occurred in three patients, who underwent conversion
      to open surgery. Two cases of paraparesis but no paraplegias or strokes were
      recorded. CONCLUSIONS: Staged procedures using endovascular grafting in the
      treatment of the arch and proximal descending thoracic aneurysm may have the
      potential to reduce morbidity and mortality rates. Although long-term results are
      still pending, this early experience demonstrates the safety and early-term
      effectiveness of this hybrid approach, which consists both of endovascular and
      open surgical procedures.

PMID- 19589694
TI  - The mode of death in the non-heart-beating donor has an impact on lung graft
      quality.
AB  - OBJECTIVE: We hypothesised that the agonal phase prior to cardiac death may
      negatively influence the quality of the pulmonary graft recovered from non-heart
      beating donors (NHBDs). Different modes of death were compared in an experimental
      model. METHODS: Non-heparinised pigs were divided into three groups (n=6 per
      group). Animals in group I [FIB] were sacrificed by ventricular fibrillation
      resulting in immediate circulatory arrest. In group II [EXS], animals were
      exsanguinated (45+/-11 min). In group III [HYP], hypoxic cardiac arrest (13+/-3
      min) was induced by disconnecting the animal from the ventilator. Blood samples
      were taken pre-mortem in HYP and EXS for measurement of catecholamine levels.
      After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored
      for 3 h (4 degrees C). Left lung performance was then tested during 60 min in our
      ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid
      was measured at the end of reperfusion. RESULTS: Pre-mortem noradrenalin (mcg l(
      1)) concentration (baseline: 0.03+/-0) increased to a higher level in HYP (50+/
      8) vs EXS (15+/-3); p=0.0074. PO(2) (mmHg) at 60 min of reperfusion was
      significantly worse in HYP compared to FIB (445+/-64 vs 621+/-25; p<0.05), but
      not to EXS (563+/-51). Pulmonary vascular resistance (dynes s cm(-5)) was
      initially higher in EXS (p<0.001) and HYP (NS) vs FIB (15824+/-5052 and 8557+/
      4933 vs 1482+/-61, respectively) but normalised thereafter. Wet-to-dry weight
      ratio was higher in HYP compared to FIB (5.2+/-0.3 vs 4.7+/-0.2, p=0.041), but
      not to EXS (4.9+/-0.2). Total protein (g l(-1)) concentration was higher,
      although not significant in HYP and EXS vs FIB (18+/-6 and 13+/-4 vs 4.5+/-1.3,
      respectively). CONCLUSION: Pre-mortem agonal phase in the NHBD induces a
      sympathetic storm leading to capillary leak with pulmonary oedema and reduced
      oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when
      recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.

PMID- 19589695
TI  - The role of b-type natriuretic peptide in heart failure management.
AB  - Heart failure is a complex clinical syndrome that manifests itself with signs and
      symptoms which are neither sensitive nor specific for the diagnosis of heart
      failure. Natriuretic peptides and in particular b-type natriuretic peptide (and
      nt-proBNP) are widely used in clinical practice around the world as a maker of
      heart failure. BNP is primarily released from the left ventricle in response to
      pressure and volume overload. The strongest evidence for the use of BNP is to
      rule in or rule out heart failure as cause of breathlessness in people who
      present to the emergency room. There is enthusiasm for use of BNP as a marker of
      heart failure severity as well as a predictor of outcomes in people with heart
      failure and trials are ongoing. Nesiritide, a recombinant form of BNP is
      currently being tested as a possible treatment in people with acutely
      decompensated heart failure.

PMID- 19589697
TI  - Fatigue estimation using a novel multi-fractal detrended fluctuation analysis
      based approach.
AB  - This paper presents a novel multi-fractal detrended fluctuation analysis-based
      approach for fatigue estimation. This approach exploits the statistical self
      similarity and long-range correlation of surface electromyography signals at
      different time scales in which the myoelectric manifestation of fatigue is more
      significant compared to the influence of varying force, muscle length (joint
      angle), and innervation zone. This approach provides a fatigue index which
      outperforms the conventional median frequency during cyclic and random
      contractions. This type of analysis is promising an efficient framework for
      analysis of surface electromyography signals with several potential applications.

PMID- 19589696
TI  - Overweight women and management of asthma.
AB  - PURPOSE: We sought to describe clinical and psychosocial characteristics of
      overweight women with asthma. METHODS: Telephone interview and medical record
      review involving 808 women with asthma participating in a randomized study to
      identify those who were overweight. We assessed the relationship of their weight
      to asthma symptoms, health care use, quality of life, self-esteem, need for
      social support, and demographic characteristics. Regression analyses were used to
      investigate relationships between overweight and asthma. FINDINGS: Sixty-eight
      percent of the women in the study were overweight or obese. Demographic
      characteristics associated with overweight in women with asthma included being
      minority (p=.000), having a lower education level (p=.000), and a lower household
      income (p=.024). Overweight was associated with greater health care use,
      comorbidities (acid reflux, urinary incontinence), and persistent disease
      (p=.001). Overweight women exhibited lower self-esteem (p=.002) and lower
      perceived quality of life (p=.000). CONCLUSION: Overweight females with asthma
      experience significant challenges because of their weight, more persistent and
      severe disease, specific comorbidities, and lower rates of obtaining psychosocial
      resources. Clinical consultations and interventions should account for the
      influence of overweight on asthma control and health status in female patients.

PMID- 19589698
TI  - Unanticipated mild-to-moderate aortic stenosis during coronary artery bypass
      graft surgery: scope of the problem and its echocardiographic evaluation.

PMID- 19589699
TI  - Conscious thought and the sustained attention to response task.
AB  - We investigated the properties of the sustained attention to response task
      (SART). In the SART, participants respond to frequent (high probability of
      occurrence) neutral signals and are required to withhold response to rare (low
      probability of occurrence) critical signals. We examined whether SART performance
      shows characteristics of speed-accuracy tradeoffs and in addition, we examined
      whether SART performance is influenced by prior exposure to emotional picture
      stimuli. Thirty-six participants in this study performed SARTs after being
      exposed to neutral and negative picture stimuli. Performance in the SART changed
      rapidly over time and there was a high correlation between participants errors of
      commission rate and their reaction time to the neutral targets (r=-.61).
      Regardless of exposure self-reported thoughts significantly correlated with both
      errors of commission and reaction times. Overall, the results support the view
      that the SART is a better measure of impulsive responding than sustained
      attention.

PMID- 19589700
TI  - Conversion to open repair after endovascular aneurysm repair: causes and results.
      A French multicentric study.
AB  - OBJECTIVE: To evaluate the causes and results of conversion to open repair after
      aortic aneurysm endovascular treatment (EVAR). DESIGN: Retrospective study of
      open conversion after EVAR was performed in eight French academic centres.
      Primary conversion (PC) within 30 days after EVAR and secondary conversions (SC)
      were analysed separately. RESULT: Between 1997 and 2007, open conversions were
      performed in 34 patients (most often in high-risk patients): 14 PC and 20 SC. Two
      main causes of PC were unfavourable iliac artery anatomy and renal artery
      coverage. In hospital mortality was 21%. SC occurred at a median of 44 months
      after primary EVAR. Nine were urgent cases for rupture or infection and 11
      elective for aneurysm growth, infection or thrombosis. Early mortality was
      similar after emergent or elective SC (25%). CONCLUSION: Open conversion, and, in
      particular, PC and urgent SC, was associated with a poor outcome. According to
      the literature, mortality after elective SC is low but remains high in high-risk
      patients.

PMID- 19589701
TI  - Ulcerated pedunculated mass of the maxillary gingiva.

PMID- 19589703
TI  - Premenarchal ovarian torsion and elevated CA-125.
AB  - BACKGROUND: Ovarian tumors are the most common gynecologic malignancy occurring
      in childhood, with germ cell tumors being most frequent. This contrasts with
      adults where epithelial tumors account for most ovarian neoplasms. Tumor markers
      are an integral part of the work-up and may guide management. CASE: A 6-year-old
      girl with a persistent adnexal mass was found to have a highly elevated CA-125.
      Other tumor markers were normal. Laparoscopy revealed an enlarged, adherent
      ovary. A minilaparotomy revealed an ovary filled with necrotic material. This
      necrotic material was excised and the ovary was spared. The pathology was
      consistent with necrosis. Follow-up ultrasonography and CA-125 were normal.
      SUMMARY AND CONCLUSIONS: This case demonstrates for the first time the
      association of an elevated CA-125 and ovarian torsion in a pediatric patient.
      This benign finding allowed attempting a conservative ovary-sparing approach
      during the surgery even in the presence of a highly elevated CA-125. However, in
      general, for children CA-125 is of limited utility, as it will not affect the
      indication for surgical exploration of persistent masses and elevations in CA-125
      may discourage ovarian conservation.

PMID- 19589702
TI  - In vitro effects of Choukroun's PRF (platelet-rich fibrin) on human gingival
      fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial
      osteoblasts in primary cultures.
AB  - OBJECTIVES: The objective of this study was to analyze the effects of Choukroun's
      PRF (platelet-rich fibrin), a leucocyte and platelet concentrate clinically
      usable as fibrin membrane or clot, on human primary cultures of gingival
      fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial
      osteoblasts. STUDY DESIGN: For the proliferation study, these cells were
      cultivated with or without a PRF membrane originating from the same donor as for
      the cells. For osteoblasts and fibroblasts, dose-dependent effect was assessed
      (using 2 membranes). Cell counts and cytotoxicity tests were performed at 3, 7,
      14, and 21 days, and even 28 days for osteoblasts. More osteoblast cultures were
      prepared in differentiation conditions according to 3 modalities (without PRF,
      with PRF, with PRF the first day and differentiation medium applied only after
      the first week of culture). Osteoblast differentiation was analyzed using Von
      Kossa staining and alkaline phosphatase, DNA and total cell proteins dosage.
      RESULTS: PRF induced a significant and continuous stimulation of proliferation in
      all cell types. It was dose dependent during all the experiment with osteoblasts,
      but only on day 14 with fibroblasts. Moreover, PRF induced a strong
      differentiation in the osteoblasts, whatever the culture conditions. The analysis
      of osteoblast cultures in differentiation conditions with PRF, using light and
      scanning electron microscopy, revealed a starting mineralization process in the
      PRF membrane itself after 14 days. Moreover, PRF leucocytes seemed to proliferate
      and interact with osteoblasts. CONCLUSIONS: Cultures with PRF are always
      cocultures with leucocytes. These "chaperone leucocytes" could be the source of
      differential geographic regulation within the culture and explain the double
      contradictory effect proliferation/differentiation observed on osteoblasts.

PMID- 19589704
TI  - Adenomyosis in the adolescent population: a case report and review of the
      literature.
AB  - BACKGROUND: This report presents a rare cause of dysmenorrhea in the adolescent
      female and the usefulness of magnetic resonance imaging (MRI) with T2 weighted
      sequence in the identification of adenomyosis. CASE: Two adolescents who
      presented with persistent pelvic pain in the absence of outflow tract obstruction
      or biopsy confirmed endometriosis had MRI-findings consistent with adenomyosis.
      SUMMARY AND CONCLUSION: In the adolescent female presenting with persistent
      dysmenorrhea, a diagnosis of adenomyosis is rare but should remain a possibility
      as one considers the differential diagnosis.

PMID- 19589705
TI  - Letter to the editor.

PMID- 19589706
TI  - Augmentation vaginoplasty of colonic neovagina stricture using oral mucosa graft.
AB  - BACKGROUND: Vaginal reconstruction is performed for a variety of congenital and
      acquired anomalies, and several techniques have been described. Conventional
      neovaginal reconstructions typically involve skin grafts or vascularized
      intestinal segments. Oral mucosa has been used successfully in urethral
      reconstruction, and several long-term studies have demonstrated its surgical
      versatility and durability. CASE REPORT: Here we present the successful use of an
      oral mucosal graft in the surgical treatment of a strictured, colonic neovagina
      in a 19-year-old, 46XX female with cloacal exstrophy. CONCLUSION: Though the
      literature contains reports of oral mucosal grafts in primary gynecologic
      surgeries, this is the first report describing the use of buccal mucosa for a
      secondary, neovagina reconstruction. Based on the outcome of our case, we
      conclude that oral mucosa is a promising graft material suitable for vaginal
      reconstructions.

PMID- 19589707
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome: sexuality, psychological effects, and
      quality of life.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital condition in which
      a genetic female is born with vaginal agenesis and a rudimentary to absent
      uterus. This condition affects a woman's ability to menstruate, to engage in
      penile-vaginal intercourse, and to bear children. Much has been published about
      how best to create a neovagina in women with MRKH, but little has been written
      about the psychological impact of MRKH and quality of life outcomes for women
      with the condition. A review of the extant literature published from 1955 to 2007
      supports that (1) surgical or non-surgical creation of a neovagina alone does not
      ensure a successful psychological outcome, (2) psychological support at critical
      times can be helpful, and (3) how professionals use language to discuss the
      condition may positively or negatively influence a female's experience of MRKH.
      This article discusses the implications that existing knowledge has on future
      research and on clinical practice. Understanding how women with MRKH cope with
      and adjust to the condition will help healthcare professionals provide optimal
      care.

PMID- 19589708
TI  - Management of vulvar hematomas: use of a Word catheter.
AB  - BACKGROUND: Large vulvar hematomas in the pediatric population resulting from
      straddle-type injuries often require surgical incision and drainage. We report an
      innovative use of a Word catheter to facilitate recovery following hematoma
      evacuation. CASE: A 14-year-old female presented with a 6-cm right labial
      hematoma and was initially treated with ice packs and analgesia. The hematoma did
      not resolve over the following weeks, and she subsequently underwent incision,
      drainage, and placement of a Word catheter. It was removed painlessly on
      postoperative day 8, and follow-up revealed no signs of reaccumulation,
      infection, or scar tissue formation. SUMMARY AND CONCLUSION: Placement of a Word
      catheter following evacuation of vulvar hematomas is a comfortable alternative to
      traditional drains to prevent reaccumulation and facilitate recovery.

PMID- 19589709
TI  - Management of ovarian dermoid cysts in the pediatric and adolescent population.
AB  - STUDY OBJECTIVE: To evaluate the surgical approach used in the management of
      ovarian dermoid cysts in the pediatric and adolescent population. DESIGN: A
      descriptive retrospective chart review of all cases of ovarian dermoid cyst
      excision between January 2001 and January 2006. SETTING: The Hospital for Sick
      Children, Toronto, Canada. PARTICIPANTS: Forty-one female children and
      adolescents who underwent operative management of an ovarian dermoid cyst. MAIN
      OUTCOME MEASURES: Surgical approach (laparoscopy vs laparotomy), intraoperative
      cyst rupture, length of hospital stay, and postoperative complications. RESULTS:
      The mean age was 12.5 years. All cysts were unilateral. Twenty-three patients
      (56%) underwent laparoscopic cystectomy, 14 (34%) underwent cystectomy via
      laparotomy, and 4 (10%) oophorectomies were performed via laparotomy. Cyst size
      was significantly larger in the laparotomy group compared to the laparoscopy
      group (mean diameter 14.4 cm vs 7.1 cm, respectively, P < .001). A significantly
      higher rate of cyst rupture was experienced during laparoscopic cystectomy
      (100%), compared to excision via laparotomy (27.7%, P < .001). Length of hospital
      stay was significantly shorter in the laparoscopy group compared to the
      laparotomy group (median of 0 vs 3 days, respectively, P < .001). A single case
      in the laparoscopy group sustained a bladder injury and developed postoperative
      necrotizing fasciitis resulting in a prolonged hospitalization and recovery.
      There were no operative or postoperative complications related to cyst content
      spillage, regardless of the surgical approach. CONCLUSION: Laparoscopic
      cystectomy is a safe and effective method of managing ovarian dermoid cysts in
      the pediatric and adolescent patient population.

PMID- 19589710
TI  - Endometriosis in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome and
      complete uterine agenesis: evidence to support the theory of coelomic metaplasia.
AB  - BACKGROUND: There are many hypotheses regarding the pathogenesis of
      endometriosis. Most theories, including retrograde menstruation, require the
      existence of a uterine structure and endometrial tissue. We report endometriosis
      with the absence of a uterus. This finding supports the theory of coelomic
      metaplasia. CASE: A 20-year-old with Mayer-Rokitansky-Kuster-Hauser syndrome
      presented with increasing pelvic pain and underwent laparoscopy. Uterine,
      cervical, vaginal, and tubal agenesis was confirmed. Stage I endometriosis was
      visualized in the posterior cul-de-sac and destroyed. She received medical
      therapy for 5 years until she represented with pain and underwent another
      laparoscopy, at which endometriosis was again identified and destroyed. SUMMARY
      AND CONCLUSION: This case of endometriosis in a patient with complete uterine
      agenesis supports the theory of coelomic metaplasia.

PMID- 19589711
TI  - Paroxysmal tonic upgaze of childhood and childhood absence epilepsy.
AB  - Paroxismal tonic upgaze of childhood (PTU) is a distinctive neuro
      ophthalmological syndrome of unknown aetiology and pathogenesis that is
      characterized by episodes of sustained upward deviation of the eyes, often with
      incomplete downward saccades on attempted downgaze. Only few cases of PTU with co
      existent epilepsy have been reported. We describe a case of female child affected
      by PTU who developed a childhood absence epilepsy (CAE) after 3 years from the
      beginning of disturbance. During hospitalization she presented repeated absence
      seizures; after the diagnosis of CAE, we started therapy with valproic acid
      (VPA). At the 6-month follow-up from the beginning of VPA therapy the child
      showed the disappearance of absence seizures with normalization of EEG, while no
      attenuation of PTU was observed. Our case suggests a possible association between
      PTU and epilepsy.

PMID- 19589712
TI  - Early decrease in resting energy expenditure with bedtime insulin therapy.
AB  - AIMS: In type 2 diabetes (T2D), insulin-induced weight gain may stem from a
      reduction in resting energy expenditure (REE). We sought to determine the early
      effects of insulin introduction on REE in 20 poorly controlled T2D patients.
      METHODS: After improving the glycaemia, REE was measured on Day 0 and Day 4
      during two treatment regimens: bedtime insulin (n=10, group 1); and one off (3
      day) intravenous insulin infusion (n=10, group 2). RESULTS: Both groups were
      similar in age, gender, BMI, C-peptide, HbA(1c) and initial REE. By Day 4,
      fasting glycaemia had similarly improved in both groups: group 1: -5.3+/
      2.7mmol/L vs group 2: -5.8+/-4.2 mmol/L. In group 2, the second REE was measured
      12h after stopping the intravenous insulin infusion, whereas subcutaneous insulin
      was maintained in group 1. REE did not change in group 2 (-1.3+/-6.5%), whereas
      it decreased significantly in group 1 (-8.0+/-7.0%; P<0.05). CONCLUSION: Bedtime
      insulin led to an early and specific reduction in REE.

PMID- 19589713
TI  - [Views of each member of an Assisted Reproductive Technologies centre on the
      embryo transfer procedure].
AB  - The embryo transfer (ET) is probably the key step of Assisted Reproductive
      Technologies (ART), end point of the collaboration of a multidisciplinary
      clinical team and an infertile couple. Thus, a perfect knowledge of available
      data regarding ET is required to optimize the results of ART. Indeed, numerous
      published studies demonstrate the impact of defined parameters onto the
      effectiveness of ET procedure. The aim of this study is to provide views of
      physicians dealing with ART, i.e. endocrinologist, ultrasound scan specialist,
      surgeon and biologist to put in perspective questions and answers about ET.

PMID- 19589714
TI  - [Questions about midwifery studies].

PMID- 19589715
TI  - Ultrasound-assisted one-pot, three-component synthesis of 1H-pyrazolo[1,2
      b]phthalazine-5,10-diones.
AB  - Triethylamine was found to be an efficient catalyst for the synthesis of 1H
      pyrazolo[1,2-b]phthalazine-5,10-diones by one-pot reaction of phthalhydrazide,
      aromatic aldehydes, and malononitrile or ethyl cyanoacetate in ethanol under
      ultrasonic irradiation. The advantages of this method are the use of an
      inexpensive and readily available catalyst, easy workup, improved yields, and the
      use of ethanol as a solvent that is considered to be relatively environmentally
      benign.

PMID- 19589716
TI  - Clinical changes of cervical dystonia pattern in long-term botulinum toxin
      treated patients.
AB  - Cervical dystonia (CD) is a complex disorder but the response to long-term
      botulinum toxin (BTX) therapy is satisfactory in most cases. Bad results are
      attributed by some authors to changes in muscle activation. Our purpose is to
      verify if the change in head deviation affects negatively the response to BTX
      therapy in a long-term follow-up, and if there are any differences in clinical
      parameters of these patients in comparison to those with stable pattern. From a
      total of 88 patients evaluated at the Movement Disorders Clinics of Hospital das
      Clinicas - University of Sao Paulo School of Medicine between January 1993 and
      December 2005, 67 were included. In 24 (35.8%) change in pattern of CD was
      observed, in a medium follow-up period of 80 months. The time between onset of
      dystonia and the diagnosis of pattern change was 9.7 years. Comparing with
      patients with no changes in CD pattern, there were no significant statistical
      differences. Improvement of symptoms around 60% was reported in both groups. In
      conclusion, the change in head deviation observed in CD was not responsible for
      bad response to therapy with BTX and there were no significant differences
      between both groups.

PMID- 19589717
TI  - The inequality hypothesis: thesis, antithesis, and a synthesis?

PMID- 19589718
TI  - Sulforaphane induces G2-M arrest and apoptosis in high metastasis cell line of
      salivary gland adenoid cystic carcinoma.
AB  - New chemotherapeutic strategy should be investigated to enhance clinical
      management in salivary gland adenoid cystic carcinoma (ACC). Recently,
      sulforaphane (SFN), as a natural compound from cruciferous vegetables exhibits a
      potent anti-cancer activity in various tumor cells, but remains uncertain in ACC
      cells. The present study examined whether SFN suppresses proliferation and in ACC
      cells, if so, the possible molecular targets would be further investigated. Cell
      survives, apoptosis, cell cycle progression and molecular targets were identified
      by multiple detecting techniques, including trypan blue dye exclusion assay,
      electron microscopy, AO/EB staining, flow cytometry and immunoblotting in human
      lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC
      M). The results showed that 5-20 microM SFN suppressed proliferation and induced
      apoptosis of ACC-M cells in dose- and time-dependent manners. Cell cycle analysis
      demonstrated treatment of ACC-M cells with 20 microM SFN resulted in G(2)/M cell
      cycle arrest, which was associated with a marked decline in protein levels of
      G(2)/M regulatory proteins including cyclin B1 and cyclin-dependent kinase 1
      (Cdk1). In terms of apoptosis, SFN increased the expression of Bax and decreased
      the level of Bcl-2 and subsequently triggered release of cytochrome c from
      mitochondria and activation of caspase-3, but Fas level and caspase-8 activity
      remained unchanged at all time points. Furthermore, levels of nuclear factor
      kappaB (NF-kappaB) p65 in both of the cytoplasm and the nucleus have also been
      markedly suppressed by SFN in a time-dependent manner. Taken together, these
      results suggest SFN inhibits cell growth via inducing G(2)/M cell arrest and
      apoptosis in ACC-M cells. These events have been associated with SFN-regulated
      multiple targets involved in ACC-M cell proliferation. The present study provides
      an evidence for testing SFN efficacy in vivo and warranting future investigations
      to exam the clinical potential of SFN in ACC chemotherapy.

PMID- 19589719
TI  - Molecular simulation of the interaction between novel type rhodanine derivative
      probe and bovine serum albumin.
AB  - The interaction between 3-(4'-methylphenyl)-5-(4'-methyl-2'-sulfophenylazo)
      rhodanine (M4MRASP) and bovine serum albumin (BSA) was studied by using
      spectrofluorimetry. It was shown in fluorescence spectrums that the quenching
      mechanism of BSA by M4MRASP was a static quenching. Meanwhile, the binding
      constant and binding site numbers were calculated. The action distance (r=8.03
      nm) and energy transfer efficiency (E=0.12) between donor (BSA) and acceptor
      (M4MRASP) were obtained according to the theory of Forster non-radiation energy
      transfer. The effect of M4MRASP on the conformation of BSA was further analyzed
      by using synchronous fluorescence spectrometry. A new model of the interaction
      between small organic molecule and biomacromolecule was established. The results
      offered a reference for the studies on the biological effects and action
      mechanism of small molecule with protein.

PMID- 19589720
TI  - Synthesis, spectral and biological studies of nitrogen-sulphur donor macrocyclic
      ligands and their transition metals complexes.
AB  - Mn(II), Co(II), Ni(II) and Cu(II) complexes have been synthesized with 22 and 24
      membered tetramide macrocyclic ligands viz; 1,9,12,20-tetraaza-2,8,13,19-tetraone
      5,16-dithiacyclodocosane [L(1)] and 1,9,13,21-tetraaza-2,8,14,20-tetraone-5,17
      dithiacyclotetracosane [L(2)] and characterized by elemental analysis, molar
      conductance, magnetic susceptibility measurements, mass, IR, electronic EPR
      spectral studies and electrochemical properties. The molar conductance of all the
      complexes in DMSO solution is corresponding to 1:2 electrolyte. Thus these
      complexes may be formulated as [M(L')]Cl(2) [where M = Mn(II), Co(II), Ni(II) and
      Cu(II) L' = L(1) and L(2)]. On the basis of spectral studies a distorted
      octahedral geometry has been assigned for all the complexes. The ligands and
      their complexes were also screened in vitro against two pathogenic fungi (F.
      moniliformae and R. solani) to assess their growth inhibiting potential.

PMID- 19589721
TI  - Optical and crystallization behavior in Dy3+ doped 40GeSe2-25Ga2Se3-35CsI glass.
AB  - Dy(3+) doped 40GeSe(2)-25Ga(2)Se(3)-35CsI (GGC) glass was synthesized, and
      optical spectrum, such as infrared transmission and Vis-Nir absorption was
      measured. Base on the Judd-Ofelt theory, the three Judd-Ofelt parameters Omega(t)
      (t=2, 4, 6) were calculated and the results were compared with other chalcogenide
      glasses. The small Omega(2) in GGC glass is ascribed to the weak covalency of Se
      Dy bond. The theory of crystallization kinetics under non-isothermal condition
      was developed, and was applied to analyze this Dy(3+) doped GGC glass. From the
      heating-rate dependence of crystallization temperature, the activation energy for
      crystallization E=148 kJ/mol is obtained, and this value is much smaller than
      that of the undoped glass host, indicating the introduction of Dy(3+) ions into
      the GGC glass will get the host crystallized easily.

PMID- 19589722
TI  - Re-emergence of another vaccine-preventable disease?-Two cases of rubella in
      older adults.
AB  - Unlike its devastating teratogenic effects, post-natal infection with rubella
      typically causes subclinical or inapparent illness. While rubella has been
      largely eliminated from the United States following the introduction of an
      efficacious live-attenuated vaccine in 1969, a small proportion of the population
      remains susceptible. Recent declining vaccination rates have resulted in a rising
      incidence of sporadic and outbreak-associated measles, reminding us that an
      increasing proportion of the population is also susceptible to, and may be
      reservoirs of transmission for, rubella. We describe two rare adult cases with no
      clear exposure. These cases serve as a reminder that clinicians should remain
      vigilant and consider rubella infection in susceptible patients, including older
      adults, presenting with febrile rash illness.

PMID- 19589723
TI  - Use of quantitative EEG in infants with port-wine birthmark to assess for Sturge
      Weber brain involvement.
AB  - OBJECTIVE: Many infants born with a facial port-wine (PW) birthmark will not
      develop brain involvement of Sturge-Weber syndrome (SWS). Previous studies have
      shown asymmetry in quantitative EEG (qEEG) correlates with degree of clinical
      impairment in children and adults with known SWS. We hope to determine if
      quantitative qEEG can be used as a method to predict which infants are most
      likely to develop SWS brain involvement on MRI. The current study looks at the
      ability of qEEG to differentiate between infants with radiographically
      demonstrated SWS and those without. METHODS: We first performed an observational
      study of qEEG results on eight infants with facial PW birthmark (four had SWS
      brain involvement). We recorded standard clinical EEGs and then derived a measure
      of asymmetry. We subsequently validated this threshold through a study of an
      additional nine infants with PW birthmark (five with SWS brain involvement).
      RESULTS: Quantitative EEG correctly identified infants with SWS brain involvement
      in all cases in the Validation cohort. This technique was at least as good as a
      pediatric electroencephalographer with extensive experience reading SWS EEGs.
      CONCLUSIONS: This study demonstrates the ability for qEEG to discriminate between
      those infants with SWS brain involvement and those with neurologically
      asymptomatic PW birthmark. SIGNIFICANCE: This study represents an important step
      toward the development of a qEEG technique able to predict which infants with PW
      birthmark will develop SWS brain involvement.

PMID- 19589724
TI  - Phylogeny and classification of Cercomonadida (Protozoa, Cercozoa): Cercomonas,
      Eocercomonas, Paracercomonas, and Cavernomonas gen. nov.
AB  - Cercomonads (=Cercomonadida) are biflagellate gliding bacterivorous protozoa,
      abundant and diverse in soil and freshwater. We establish 56 new species based on
      165 cultures, differential interference contrast microscopy, and 18S and ITS2
      rDNA sequencing, and a new genus Cavernomonas studied by scanning electron
      microscopy. We fundamentally revise the phylogeny and classification of
      cercomonad Cercozoa. We describe 40 Cercomonas species (35 novel), six
      Eocercomonas (five novel), two Cavernomonas, and 18 Paracercomonas species (14
      novel). We obtained additional cercomonad clade A (Cercomonas, Eocercomonas,
      Cavernomonas) sequences from multiple environmental DNA libraries. The most
      commonly cultivated genotypes are not the commonest in environmental DNA,
      suggesting that cercomonad ecology is far more complex than implied by laboratory
      cultures. Cercomonads have never been isolated from saline environments, although
      some species can grow in semi-saline media in the laboratory, and environmental
      DNA libraries regularly detect them in coastal marine sediments. The first
      ultrastructural study of an anaerobic cercozoan, Paracercomonas anaerobica sp.
      nov., a highly divergent cercomonad, shows much simpler ciliary roots than in
      clade A cercomonads, a ciliary hub-lattice and axosome, and mitochondria with
      tubular cristae, consistent with it being only facultatively anaerobic. We also
      describe Agitata tremulans gen. et sp. nov., previously misidentified as
      Cercobodo (=Dimastigamoeba) agilis Moroff.

PMID- 19589725
TI  - Revised and new reference values for environmental pollutants in urine or blood
      of children in Germany derived from the German environmental survey on children
      2003-2006 (GerES IV).
AB  - Based on the representative data collection of the German Environmental Survey on
      Children 2003-2006 (GerES IV) the Human Biomonitoring Commission of the German
      Federal Environment Agency has updated the reference values for a comprehensive
      number of environmental pollutants in blood and urine of children in Germany.
      Reference values are statistically derived values that indicate the upper margin
      of background exposure to a given pollutant in a given population at a given
      time. They can be used as criteria to classify the measured values of individuals
      or population groups as being "elevated" or "not elevated". Since environmental
      conditions are changing, reference values are continuously checked and updated if
      new information becomes available. Therefore, the previously derived reference
      values for metabolites of pyrethroids (cis-, trans-Cl(2)Ca and 3-PBA: 1, 2, and
      2microg/l), of PAH (1-hydroxypyrene: 0.5microg/l), for arsenic in urine
      (15microg/l), and for PCB 138, PCB 153, PCB 180 in whole blood (0.3, 0.4,
      0.3microg/l) and for DDE (western Germany) in whole blood (0.7microg/l) were
      confirmed. The following reference values were lowered: lead in blood from 50 to
      35microg/l, cadmium in urine from 0.5 to 0.2microg/l, mercury in whole blood from
      1.0 to 0.8microg/l, mercury in urine from 0.7 to 0.4microg/l, beta-HCH in whole
      blood from 0.3 to 0.1microg/l, HCB in whole blood from 0.3 to 0.2microg/l, and
      DMP in urine from 135 to 75microg/l, and DMTP in urine from 160 to 100microg/l.
      Based on the extended data set of the GerES IV, the reference value for the sum
      of PCB 138+153+180 in whole blood of children aged 7 to 14 was raised from 0.9 to
      1.0microg/l. The reference value for DEP in urine of children aged 3 to 14 was
      raised from 16 to 30microg/l. New reference values in urine of children aged 3 to
      14 living in Germany were derived for antimony (0.3microg/l), nickel
      (4.5microg/l), thallium (0.6microg/l), uranium (0.04microg/l), metabolites of
      organophosphorous compounds (DMDTP, DETP: 10microg/l, 10microg/l) and metabolites
      of PAH (1-hydroxyphenanthrene: 0.6microg/l; 2/9-hydroxyphenanthrene: 0.4microg/l;
      3-hydroxyphenanthrene: 0.5microg/l; 4-hydroxyphenanthrene: 0.2microg/l; Sigma
      hydroxyphenanthrene (1, 2/9, 3, 4): 1.5microg/l) in urine and for DDE in blood of
      children aged 7 to 14 years living in eastern Germany (1.4microg/l). If reliable
      and repeated measurements show a value above the reference value, an
      environmental hygiene-based search for the causes and sources of this exposure is
      recommended. After that, it should be checked whether the exposure can be
      decreased within reasonable bounds.

PMID- 19589726
TI  - Real-time versus post-game GPS data in team sports.
AB  - Real-time (RT) GPS is used to monitor performance during Australian Football
      matches. Typically athlete targets monitored in RT are set from post-game (PG)
      data. The validity of RT compared to PG data is not yet known. This study
      compared RT data for key parameters to those obtained PG, using MinimaxX GPS. RT
      was different to PG for jog 4.2-5.0, run 5.0-6.9, sprint 6.9-10.0 m s(-1), and
      total distance (CV=6.4-19.6%). The signal to noise ratio was low for jog and run
      distance. For sprint noise exceeded the signal, with the opposite true for total
      distance. Caution must be applied if using RT data to monitor performance,
      especially if targets are set for players using PG data.

PMID- 19589727
TI  - Inflammation and pancreatic cancer: an evidence-based review.
AB  - There is a growing awareness that inflammation plays a contributory role in
      numerous pathologies, including pancreatic carcinogenesis. Inflammatory states
      are characterized by the creation of reactive oxygen species and the induction of
      cell cycling for tissue growth and repair. The initiation, promotion and
      expansion of tumors may be influenced by numerous components that function in the
      inflammatory response. Recognized risk factors for pancreatic cancer include
      cigarette smoking, chronic/hereditary pancreatitis, obesity and type II diabetes.
      Each risk factor is linked by the fact that the inflammatory state significantly
      drives its pathology. This article will outline how inflammatory mechanisms are
      etiologically linked to pancreatic adenocarcinoma.

PMID- 19589728
TI  - Inflammation and colorectal cancer.
AB  - Patients with long-standing inflammatory bowel disease (IBD) have an increased
      risk of developing colorectal cancer (CRC). However, the underlying mechanisms
      are not entirely clear. A genetic basis for the increased risk of CRC in IBD
      patients is only a partial explanation. It is possible that high levels of
      inflammatory mediators that are produced in this setting may contribute to the
      development and progression of CRC. Growing evidence supports a role for various
      cytokines, released by epithelial and immune cells, in the pathogenesis of IBD
      associated neoplasia. Two key genes in the inflammatory process, cyclooxygenase-2
      (COX-2) and nuclear factor kappaB (NF-kappaB), provide a mechanistic link between
      inflammation and cancer while other factors such as, TNF-alpha and IL-6-induced
      signaling have been recently shown to promote tumor growth in experimental models
      of colitis-associated cancer. This article reviews the pathogenesis of IBD
      related CRC and summarizes the molecular mechanisms underlying the development of
      intestinal neoplasia in the setting of chronic inflammation.

PMID- 19589729
TI  - Heart failure patients' perceptions on nutrition and dietary adherence.
AB  - INTRODUCTION: The purpose of this study was to explore patients' perception about
      how the foods they eat impact heart failure (HF) symptoms, their understanding of
      dietary recommendations received, and factors affecting their adherence to
      dietary recommendations that include recommendations to follow a low sodium diet
      and a low-fat diet. METHODS: Qualitative data were obtained from 20 patients
      using semi-structured interviews. RESULTS: The majority of patients believed that
      food intake could impact their health, but less than half thought sodium could
      affect HF symptoms. Eighty-five percent of patients received recommendations for
      a specific diet, but only 60% reported following them. Factors identified as
      affecting adherence included: a) knowledge, b) social pressure and encouragement
      from others, c) social situations, and d) food as a source of pleasure and
      enjoyment. CONCLUSION: Ability to follow dietary recommendations remains a
      problem for many patients. Patients identified several key factors that affected
      ability to follow dietary recommendations. Strategies that target these factors
      may promote patients' decision to follow dietary recommendations and enhance
      their ability to do so.

PMID- 19589731
TI  - Robotic-assisted laparoendoscopic single-site surgery in gynecology: initial
      report and technique.
AB  - Robotic surgery has greatly improved surgeon dexterity and ergonomics but has
      substantially increased the number and size of ports required. The typical
      robotic surgical procedure will use three 8-mm ports and two 12-mm ports. Single
      port laparoscopy, also known as Laparo-Endoscopic Single Site (LESS) surgery, is
      an attempt to further enhance cosmetic benefits and reduce morbidity of minimally
      invasive surgery.We present our initial clinical experience and technique with
      robotic-assisted single-port surgery in gynecology.

PMID- 19589732
TI  - Laparoscopic removal of mesh used in pelvic floor surgery.
AB  - Various meshes are being used widely in clinical practice for pelvic
      reconstructive surgery despite the lack of evidence of their long-term safety and
      efficacy. Management of complications such as mesh erosion and dyspareunia can be
      challenging. Most mesh-related complications can probably be managed successfully
      via the transvaginal route; however, this may be impossible if surgical access is
      poor. This case report demonstrates the successful laparoscopic removal of mesh
      after several failed attempts via the vaginal route.

PMID- 19589730
TI  - Vaccination with tumor cells pulsed with foreign peptide induces immunity to the
      tumor itself.
AB  - EMT-6 mammary carcinoma and B16 melanoma (B16M) cells are lethal and barely
      immunogenic in syngeneic BALB/c and C57BL/6 mice, respectively. We show that mice
      vaccinated with tumor cells pulsed with a MHC class I-restricted peptide develop
      a T cell response, not only to the peptide, but also to the unpulsed tumor. These
      mice display protective immunity against the unpulsed tumor, and their T cells
      adoptively transfer tumor-specific protection to immunodeficient SCID mice. Our
      data have implications for cancer vaccine strategies. Grafting a single well
      defined foreign peptide on tumor cells might suffice to trigger anti-tumor
      immunity.

PMID- 19589733
TI  - Inhibition of RVLM synaptic activation at peak hyperthermia reduces visceral
      sympathetic nerve discharge.
AB  - Hyperthermia is an environmental stressor that produces marked increases in
      visceral sympathetic nerve discharge (SND) in young rats. The brainstem in rats
      contains the essential neural circuitry for mediating visceral sympathetic
      activation; however, specific brainstem sites involved remain virtually unknown.
      The rostral ventral lateral medulla (RVLM) is a key central nervous system region
      involved in the maintenance of basal SND and in mediating sympathetic nerve
      responses evoked from supraspinal sites. In the present study we tested the
      hypothesis that inhibition of RVLM synaptic activation at peak hyperthermia
      (internal body temperature, Tc, increased to 41.5 degrees C) would affect heating
      induced visceral sympathetic activation. Experiments were completed in chloralose
      urethane anesthetized, baroreceptor-intact and sinoaortic-denervated, 3-6 month
      old Sprague-Dawley rats. Bilateral inhibition of RVLM synaptic activation
      produced by muscimol microinjections (400 and 800 pmol) at 41.5 degrees C
      resulted in immediate and significant reductions in peak heating-induced renal
      and splenic sympathoexcitation. Interruption of RVLM synaptic activation and
      axonal transmission by lidocaine microinjections (40 nmol) at 41.5 degrees C
      produced significant reductions in hyperthermia-induced sympathetic activation to
      similar levels produced by RVLM muscimol microinjections. The total amount of SND
      inhibited by RVLM muscimol and lidocaine microinjections was significantly more
      during hyperthermia (41.5 degrees C) than normothermia (38 degrees C). These
      findings demonstrate that maintenance of sympathetic activation at peak
      hyperthermia is dependent on the integrity of RVLM neural circuits.

PMID- 19589735
TI  - Determination of mitragynine in rat plasma by LC-MS/MS: application to
      pharmacokinetics.
AB  - This study used for the first time LC-MS/MS for the analysis of mitragynine
      (MIT), a mu-opioid agonist with antinociceptive and antitussive properties, in
      rat plasma. Mitragynine and the internal standard (amitriptyline) were extracted
      from plasma with hexane-isoamyl alcohol and resolved on a Lichrospher RP-SelectB
      column (9.80 and 12.90 min, respectively). The quantification limit was 0.2 ng/mL
      within a linear range of 0.2-1000 ng/mL. The method was applied to quantify
      mitragynine in plasma samples of rats (n=8 per sampling time) treated with a
      single oral dose of 20 mg/kg. The following pharmacokinetic parameters were
      obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum
      plasma concentration: 1.26 h; elimination half-life: 3.85 h, apparent total
      clearance: 6.35 L/h/kg, and apparent volume of distribution: 37.90 L/kg.

PMID- 19589734
TI  - Distinct kinetics of human DNA ligases I, IIIalpha, IIIbeta, and IV reveal direct
      DNA sensing ability and differential physiological functions in DNA repair.
AB  - The three human LIG genes encode polypeptides that catalyze phosphodiester bond
      formation during DNA replication, recombination and repair. While numerous
      studies have identified protein partners of the human DNA ligases (hLigs), there
      has been little characterization of the catalytic properties of these enzymes. In
      this study, we developed and optimized a fluorescence-based DNA ligation assay to
      characterize the activities of purified hLigs. Although hLigI joins DNA nicks, it
      has no detectable activity on linear duplex DNA substrates with short, cohesive
      single-strand ends. By contrast, hLigIIIbeta and the hLigIIIalpha/XRCC1 and
      hLigIV/XRCC4 complexes are active on both nicked and linear duplex DNA
      substrates. Surprisingly, hLigIV/XRCC4, which is a key component of the major non
      homologous end joining (NHEJ) pathway, is significantly less active than hLigIII
      on a linear duplex DNA substrate. Notably, hLigIV/XRCC4 molecules only catalyze a
      single ligation event in the absence or presence of ATP. The failure to catalyze
      subsequent ligation events reflects a defect in the enzyme-adenylation step of
      the next ligation reaction and suggests that, unless there is an in vivo
      mechanism to reactivate DNA ligase IV/XRCC4 following phosphodiester bond
      formation, the cellular NHEJ capacity will be determined by the number of
      adenylated DNA ligaseIV/XRCC4 molecules.

PMID- 19589736
TI  - Development and validation of a quantitative assay for the analysis of tamoxifen
      with its four main metabolites and the flavonoids daidzein, genistein and
      glycitein in human serum using liquid chromatography coupled with tandem mass
      spectrometry.
AB  - The development and validation of a bioanalytical assay is described for the
      simultaneous analysis in human serum of tamoxifen, four of its main metabolites
      and three flavonoids, which are known constituents in alternative medicine and
      dietary supplements often used by breast cancer patients. The method has been
      fully validated at linear ranges covering steady-state serum concentrations in
      patients who receive therapeutic dosages of tamoxifen. The wide range also allows
      for quantification of large inter-patient fluctuations of flavonoid
      concentrations. The bioanalytical assay is based on reversed phase liquid
      chromatography coupled with tandem mass spectrometry in the positive ion mode
      using multiple reaction monitoring for drug (-metabolite) quantification. The
      sample pretreatment consists of a protein precipitation with acetonitrile using
      only 50 microL serum. The described method is simple, robust and reproducible
      with inter- and intra-assay accuracies within 85-115%. The applicability of the
      assay was demonstrated and it is now successfully used to study the in vivo
      pharmacokinetics of tamoxifen, its main metabolites and flavonoids in human serum
      of patients receiving tamoxifen.

PMID- 19589737
TI  - Fluorescent probes for the structure and function of metallothionein.
AB  - Fluorescence methods have been instrumental in demonstrating that the structure
      of human metallothionein in vivo depends on the availability of metal ions and
      the redox environment. Differential chemical modifications of its cysteine thiols
      with fluorescent probes allowed determination of three states: metallothionein
      (zinc-bound thiolate), thionein (free thiols), and thionin (disulfides).
      Interrogation of its zinc-binding properties with fluorescent chelating agents
      revealed that the affinities for the seven zinc ions vary over four orders of
      magnitude. Attachment of fluorescent labels generated metallothionein FRET
      (fluorescence resonance energy transfer) sensors for investigating its structure
      and function in living cells.

PMID- 19589738
TI  - Beware--raising a DIEP flap post abdominal laparoscopic surgery.

PMID- 19589739
TI  - Aesthetic "Gull-wing" type incision for minimising postoperative scar contracture
      in the chin bone graft procedure.

PMID- 19589741
TI  - Posterior compartment of the lower leg reconstruction with free functional rectus
      femoris transfer after sarcoma resection.
AB  - A 72-year-old man with the third recurrence of a low-grade liposarcoma of the
      right lower leg came to our attention seeking limb-salvage surgery. The tumour
      was removed en bloc with all the superficial posterior compartment of the leg.
      Appropriate foot flexion was restored by means of a free-functional rectus
      femoris musculocutaneous flap harvested from the ipsilateral thigh. The patient
      was kept on a postoperative splint for 6 weeks. Three months after the operation,
      clinical and elecromyographic signs of reinnervation were observed. The patient
      was able to walk, run and climb stairs and no donor-site morbidity was observed.
      Thigh extension was rated M4, comparable to the contralateral thigh. Foot
      flexion, without any postoperative exercise, was rated M3 with a 30 degrees
      excursion. To the best of our knowledge, this is the first report of
      reconstruction of the posterior compartment of the leg r with a free functional
      rectus femoris flap. We believe this muscle could be the ideal option for such
      reconstruction.

PMID- 19589740
TI  - Surgical treatment of a basal cell carcinoma in the upper forehead area by
      combination of reconstructive and aesthetic surgical techniques.

PMID- 19589742
TI  - [Is clinical judgment a suitable method to select marginal allograft for
      transplantation? A single centre experience].
AB  - In order to deal with the organ shortage, the use of organs from marginal donors
      has emerged as an obvious option. The decision to accept a kidney from an
      expanded criteria donor is left to the transplantation centre. This study was
      carried out to evaluate whether clinical judgment is a suitable method to decline
      a kidney from a marginal donor. This was a retrospective study of the outcome of
      marginal kidneys rejected by our centre between 1st January 2000 and 31st
      December 2006 but accepted by another centre. The decision to refuse a marginal
      kidney was based on the clinical judgment of the nephrologists on call. Kidney
      refusal was retrospectively considered as a "mistaken decision" when the kidney
      was transplanted in another centre and when the estimated GFR was above 60
      mL/min/1.73 m(2) one year after transplantation. The DD score was calculated
      retrospectively for every rejected kidney. During the study period, 304 kidneys
      were not accepted for transplantation. Of these 304 kidneys, 55 marginal kidneys
      were not accepted by the nephrologists on call. Among these 55 marginal kidneys,
      44 were accepted and transplanted in another centre. Early graft loss occurred in
      2/44 recipients. Death censored allograft survival at one and two years was
      retrospectively 98 and 93%. Kidney refusal was considered as a "mistaken
      decision" for 12/44 rejected kidneys. Of these 12 rejected kidneys, only two
      could have been considered as marginal kidneys by the DD score, as compared with
      27/30 of the remaining rejected kidneys. Our study shows that clinical judgment
      alone is not a suitable method for selecting marginal donors. Proven definitions
      of "marginal donor", available to physicians when the medical decision has to be
      made, may help nephrologists in their clinical practice.

PMID- 19589743
TI  - [Renal diseases in cystic fibrosis].
AB  - Patients with cystic fibrosis (CF) show a continuing improvement in their life
      expectancy thanks to advances in knowledge of this disorder, allowing better
      multidisciplinary routine monitoring and earlier therapeutic interventions.
      Likewise, more than of 40% of these patients are adults and CF is no more only a
      pediatric disease. Due to their higher life expectancy, CF patients present new
      and unusual complications that were not recorded before. Among them, some renal
      disorders have to be added to the CF-related renal diseases. They are due to
      frequent and prolonged exposure to various potentially nephrotoxic factors that
      need to be taken into account early enough in order to avoid renal failure :
      essentially risk factors for kidney stones formation, bacterial infections with
      their associated immune complexes diseases, nephrotoxic effects of antibiotics,
      diabetes mellitus. Because we observed a case of IgA glomerulonephritis in a 35
      year-old patient with cystic fibrosis, we have searched about all these renal
      consequences due to this affection and here report them.

PMID- 19589745
TI  - Investigation on how renewal of complete dentures impact on dietary and nutrient
      adequacy in edentulous patients.
AB  - PURPOSE: The aim of this study is to investigate changes of diet and nutrient
      adequacy between complete denture wearers with their existing dentures and those
      with new dentures. METHODS: After obtained their written informed consent 30
      patients who visited Nihon University School of Dentistry at Matsudo Affiliated
      Hospital from March 2004 to November 2005 were asked to record their 3
      consecutive day's meals and to take a picture of them. Furthermore, foods which
      they can eat with their dentures were examined the questionnaire developed by
      Hirai. Referring to the obtained records and pictures, one dietitian interviewed
      to confirm the exact intakes of meals. In addition, the masticatory ability was
      calculated using the questionnaire. The nutrient adequacy and masticatory score
      determined at the time of the first and second survey were examined by repeated
      measures ANOVA. A p-value less than 0.05 was considered statistically
      significant. RESULT: The total intake of energy and nutrients was almost over
      100% in both the groups. However, no statistically significant difference was
      obtained. The masticatory score with the existing and new denture were 66.1+/
      18.5 and 58.3+/-19.9, respectively. The score increased significantly in the new
      denture group when compared with that of the existing denture group. CONCLUSION:
      The self-evaluation of the masticatory function improved after the switch from
      the old to new dentures.

PMID- 19589744
TI  - Influence of methyl mercaptan at early setting stages on the properties of self
      curing addition silicone resilient denture lining materials.
AB  - PURPOSE: The aim of the present study was to clarify the influence of early
      setting conditions on the properties of self curing addition silicone resilient
      denture lining materials. METHODS: Four auto-mix types of commercial self curing
      addition silicone resilient denture lining materials were used. Agar plates
      containing various concentrations of methyl mercaptan (MMP) were prepared and
      cylindrical specimens (10mm in height and 10mm in diameter) of silicone liners
      were set on the agar plate. The Shore A hardness of the agar-contacted surface of
      the specimen was measured at 0, 1, 7 and 28 days after stored in 37 degrees C
      water. The viscoelastic properties (instantaneous elastic modulus, coefficient of
      viscosity and permanent deformation) of two silicone liners, which showed a great
      decrease in the Shore A hardness by agar contact, were determined by a creep
      meter. RESULTS: The Shore A hardness, coefficient of viscosity, and instantaneous
      elastic modulus deceased when the specimen was set on the MMP containing agar
      plate, but the permanent deformation of these specimens increased. CONCLUSION:
      The exposure to MMP at the early setting stage influenced the properties of self
      curing addition silicone resilient denture lining materials.

PMID- 19589746
TI  - Universal perceptron and DNA-like learning algorithm for binary neural networks:
      non-LSBF implementation.
AB  - Implementing linearly nonseparable Boolean functions (non-LSBF) has been an
      important and yet challenging task due to the extremely high complexity of this
      kind of functions and the exponentially increasing percentage of the number of
      non-LSBF in the entire set of Boolean functions as the number of input variables
      increases. In this paper, an algorithm named DNA-like learning and decomposing
      algorithm (DNA-like LDA) is proposed, which is capable of effectively
      implementing non-LSBF. The novel algorithm first trains the DNA-like offset
      sequence and decomposes non-LSBF into logic XOR operations of a sequence of LSBF,
      and then determines the weight-threshold values of the multilayer perceptron
      (MLP) that perform both the decompositions of LSBF and the function mapping the
      hidden neurons to the output neuron. The algorithm is validated by two typical
      examples about the problem of approximating the circular region and the well
      known n-bit parity Boolean function (PBF).

PMID- 19589747
TI  - Distributed coordination of networked fractional-order systems.
AB  - This paper studies the distributed coordination of networked fractional-order
      systems over a directed interaction graph. A general fractional-order
      coordination model is introduced by summarizing three different cases: 1)
      fractional-order agent dynamics with integer-order coordination algorithms; 2)
      fractional-order agent dynamics with fractional-order coordination algorithms;
      and 3) integer-order agent dynamics with fractional-order coordination
      algorithms. We show sufficient conditions on the interaction graph and the
      fractional order such that coordination can be achieved using the general model.
      The coordination equilibrium is also explicitly given. In addition, we
      characterize the relationship between the number of agents and the fractional
      order to ensure coordination. Furthermore, we compare the convergence speed of
      coordination for fractional-order systems with that for integer-order systems. It
      is shown that the convergence speed of the fractional-order coordination
      algorithms can be improved by varying the fractional orders with time. Finally,
      simulation results are presented as a proof of concept.

PMID- 19589748
TI  - Skin infection masquerading as lupus erythematosous profundus.

PMID- 19589749
TI  - Deep soft tissue leiomyoma of the thigh.

PMID- 19589750
TI  - Splenic actinomycosis presenting as subcutaneous abscesses.

PMID- 19589751
TI  - Aseptic olecranon bursitis as a novel subcutaneous manifestation of
      dermatomyositis.

PMID- 19589752
TI  - Photoallergic contact dermatitis in a pig farmer, caused by cotrimoxazole.

PMID- 19589753
TI  - Vaccine supply, demand, and policy: a primer.
AB  - OBJECTIVE: To provide an overview of supply and demand issues in the vaccine
      industry and the policy options that have been implemented to resolve these
      issues. DATA SOURCES: Medline, Policy File, and International Pharmaceutical
      Abstracts were searched to locate academic journal articles. Other sources
      reviewed included texts on the topics of vaccine history and policy, government
      agency reports, and reports from independent think tanks. Keywords included
      vaccines, immunizations, supply, demand, and policy. STUDY SELECTION: Search
      criteria were limited to English language and human studies. Articles pertaining
      to vaccine demand, supply, and public policy were selected and reviewed for
      inclusion. DATA EXTRACTION: By the authors. DATA SYNTHESIS: Vaccines are biologic
      medications, therefore making their development and production more difficult and
      costly compared with "small-molecule" drugs. Research and development costs for
      vaccines can exceed $800 million, and development may require 10 years or more.
      Strict manufacturing regulations and facility upgrades add to these costs. Policy
      options to increase and stabilize the supply of vaccines include those aimed at
      increasing supply, such as government subsidies for basic vaccine research,
      liability protection for manufacturers, and fast-track approval for new vaccines.
      Options to increase vaccine demand include advance purchase commitments,
      government stockpiles, and government financing for select populations.
      CONCLUSION: High development costs and multiple barriers to entry have led to a
      decline in the number of vaccine manufacturers. Although a number of vaccine
      policies have met with mixed success in increasing the supply of and demand for
      vaccines, a variety of concerns remain, including developing vaccines for complex
      pathogens and increasing immunization rates with available vaccines. New policy
      innovations such as advance market commitments and Medicare Part D vaccine
      coverage have been implemented and may aid in resolving some of the problems in
      the vaccine industry.

PMID- 19589754
TI  - Pharmacy school at "40 something".

PMID- 19589756
TI  - Pharmacy's stars climb to reach our potential.

PMID- 19589755
TI  - APhA2009 House of Delegates: serving the association and the profession.

PMID- 19589757
TI  - The pharmacist will see you now.

PMID- 19589758
TI  - Providing maximal patient care, improving patient safety.

PMID- 19589759
TI  - Report of the 2009 APhA House of Delegates: actions of the legislative body of
      the American Pharmacists Association.

PMID- 19589762
TI  - Sustainability of pharmacy-based innovations: the case of in-house immunization
      services.
AB  - OBJECTIVE: To examine the effect of organization-level factors on sustainability
      of pharmacy-based in-house immunization services. DESIGN: Cross-sectional study.
      SETTING: Washington State community pharmacies in 2006. PARTICIPANTS: Key
      informants of 490 community pharmacies. INTERVENTION: Mixed-mode survey; five
      mail and telephone contacts were used. MAIN OUTCOME MEASURES: Effectiveness of
      champions (i.e., influential individuals within the host organization who
      actively and continuously promote the service), formal evaluation process, degree
      of modifications made to in-house services, degree of compatibility between in
      house services and the host pharmacy, and sustainability of in-house immunization
      services were measured and included in the proposed model. Using survey
      responses, factor analysis and path analysis were performed to determine the
      relationships among these variables. RESULTS: Of the 490 survey instruments sent,
      1 was undeliverable, 2 were incomplete, and 206 were completed (42.1% response
      rate). A total of 104 pharmacies that reported offering immunization services in
      2006 were included in the analysis. Compatibility, which was defined as the fit
      between in-house immunization services and the host pharmacy, was the key to
      sustainability of immunization services. To enhance compatibility between in
      house services and the host pharmacy, two pathways were found. First, in-house
      services underwent formal evaluations and subsequent modifications were made to
      the services. The second pathway bypassed the adaptation process. Through the
      second pathway, an operational champion implemented in-house services in a way
      that was already compatible with the host pharmacy. CONCLUSION: Organizational
      leaders and practitioners had the potential to sustain in-house services. The key
      factors included in the model should be incorporated as an integral part of
      programs planning to foster sustainability of in-house immunization services.

PMID- 19589763
TI  - Exploring the formation of patient satisfaction in rural community
      telepharmacies.
AB  - OBJECTIVES: To apply a previously validated patient satisfaction questionnaire
      within rural community telepharmacies in an effort to identify the underlying
      factors determining satisfaction with those services and to assess whether the
      latent structure(s) of patient satisfaction varies depending on delivery mode or
      communityspecific factors. DESIGN: Descriptive, nonexperimental, cross-sectional
      study. SETTING: Eight rural community telepharmacy sites (seven in North Dakota
      and one in Minnesota) in fall 2005. PATIENTS: 400 potential participants in rural
      communities (response rate 24% [n = 96]) whose primary community pharmacy is a
      telepharmacy site. INTERVENTION: PATIENTS visiting a pharmacy to have at least
      one prescription filled were asked to complete a survey and mail responses to the
      investigators. The survey contained 37 questions, the first 20 of which were
      adapted from a well-established, validated survey instrument. MAIN OUTCOME
      MEASURE: Patient satisfaction with rural community telepharmacy services; patient
      responses to 20 questions in the survey were used as main outcome variables.
      RESULTS: Applying factor analysis to the data yielded a single dimension of
      patient satisfaction. CONCLUSION: A previous application of this instrument in a
      traditional community pharmacy setting yielded two interrelated latent constructs
      ("friendly explanation" and "managing therapy"). Our analysis suggests that the
      formation of patient satisfaction in rural community telepharmacies is much
      simpler in that patients form a single construct exhibiting high mean and median
      values. Anecdotal evidence from the literature suggests that the formation of a
      single construct reflects patients' desire to retain a point of access to health
      care in their communities.

PMID- 19589765
TI  - Evaluation of community health screening participants' knowledge of
      cardiovascular risk factors.
AB  - OBJECTIVES: To assess knowledge of cardiovascular disease (CVD) risk factors
      among a group of health screening participants and to compare knowledge between
      participants with high and low CVD risk. DESIGN: Cross-sectional pilot study.
      SETTING: Jonesboro, AR, during June 2007. PATIENTS: 121 adult volunteers
      participating in a community health screening. INTERVENTION: 34-item self
      administered written questionnaire. MAIN OUTCOME MEASURES: Ability to identify
      CVD risk factors and healthy values for CVD risk factors and the differences in
      these abilities between participants with high and low CVD risk. RESULTS:
      Participants demonstrated good knowledge of traditional CVD risk factors such as
      high blood pressure, high cholesterol, lack of exercise, and overweight or obese
      status. Knowledge of other CVD risk factors and healthy values for major CVD risk
      factors was limited. Participants with high CVD risk were significantly more
      likely to correctly identify high triglycerides as a CVD risk factor and to
      identify healthy values for fasting blood glucose and total cholesterol compared
      with participants with low CVD risk. CONCLUSION: Overall, participants lacked
      knowledge of the risk factor status and healthy values for many CVD risk factors.
      Participants with high CVD risk may have better knowledge of some CVD risk
      factors than participants with low CVD risk. These findings highlight the need
      for more education to improve knowledge in both risk groups.

PMID- 19589764
TI  - Nonmedical use of prescription opioids and stimulants among student pharmacists.
AB  - OBJECTIVES: To examine the prevalence and patterns of nonmedical use of
      prescription opioid analgesics and stimulants among student pharmacists. DESIGN:
      Descriptive, nonexperimental, cross-sectional study. SETTING: Private urban
      college of pharmacy in the United States in fall 2006. PARTICIPANTS: 1,538 PharmD
      students. INTERVENTION: Online survey. MAIN OUTCOME MEASURES: Lifetime and past
      year nonmedical prescription opioid and stimulant use. RESULTS: Response rate for
      the survey was 62%. Lifetime prevalence of opioid misuse was 8%, and 5% of
      students had misused in the past year. Lifetime prevalence of stimulant misuse
      was 7%, and 5% had misused in the past year. Whites and fraternity or sorority
      members were more likely than their peers to have ever misused opioids. Past-year
      opioid misuse was more likely among whites, men, and low academic achievers
      compared with their peers. Lifetime stimulant misuse was more likely among
      students who were white, older, and fraternity or sorority members, while past
      year misuse was more likely among whites and low academic achievers. Common
      motives for opioid misuse were to have fun, to relax, and to deal with chronic
      pain. Stimulants were used to improve concentration and academic performance.
      Friends were the most common source of prescription opioids and stimulants.
      Nonmedical prescription use was associated with greater likelihood of alcohol and
      other illicit substance use. CONCLUSION: The prevalence of prescription
      medication misuse among student pharmacists was lower than (opioids) or
      comparable with (stimulants) reported rates in college populations. Subgroups of
      students demonstrated higher rates of nonmedical use, including whites, students
      involved with fraternities or sororities, and low academic achievers. That
      friends were the primary source of misused medications indicates that diversion
      of prescription-only controlled substances likely occurs among student
      pharmacists. Nonmedical prescription medication use should be considered in the
      context of other substance use.

PMID- 19589767
TI  - Assessing the impact of lifestyle modification education on knowledge and
      behavior changes in gastroesophageal reflux disease patients on proton pump
      inhibitors.
AB  - OBJECTIVES: To assess patients' knowledge of gastroesophageal reflux disease
      (GERD) lifestyle modifications and to identify patients' behaviors associated
      with GERD management before and after an educational intervention. METHODS: The
      study was conducted at five indigent health centers in Columbus, OH, from January
      to May 2007. A total of 30 adult patients with GERD receiving proton pump
      inhibitor (PPI) therapy were assessed. In both the control and intervention
      groups, a pretest consisting of 23 questions assessed patients' knowledge
      regarding GERD and lifestyle modifications. A presurvey consisting of eight
      questions assessed patients' current behaviors associated with GERD management
      using both lifestyle modifications and PPIs. The intervention group also received
      approximately 10 minutes of education on lifestyle modifications. A posttest and
      postsurvey were given 8 to 12 weeks after the initial session to both groups.
      Main outcome measures included change in test score for patients in the control
      versus intervention groups. Outcomes measured on the pre- and postsurvey included
      source of heartburn information/education, smoking status, trigger foods eaten
      weekly, frequency of monthly heartburn episodes, and PPI adherence. RESULTS: The
      average change in test scores was 1.33 and 2.73 in the control and intervention
      groups, respectively (P = 0.11; two-sample t test). The frequency of monthly
      heartburn episodes increased postsurvey in the control group; however, the
      frequency of monthly episodes decreased in the intervention group. For the
      presurvey, no patients reported ever having received GERD education from a
      pharmacist. For the postsurvey, all 15 patients in the intervention group stated
      that they had received education from a pharmacist. CONCLUSION: The intervention
      group patients had higher mean change in test scores compared with the control
      group, although this difference did not reach statistical significance. The
      failure to achieve statistical significance may have resulted from the small
      sample size. The pharmacist-patient interaction improved patient knowledge and
      some behaviors made in GERD management and symptom reduction.

PMID- 19589766
TI  - Multistate survey of primary care physician and midlevel provider attitudes
      toward community pharmacists.
AB  - OBJECTIVES: To assess and compare the attitudes of primary care physicians and
      midlevel providers toward community pharmacists by surveying the frequency and
      perceived helpfulness of practitioner-pharmacist interactions, as well as
      attitudes toward traditional and expanded functions. METHODS: A sample of primary
      care physicians, physician assistants, and nurse practitioners (n = 3,851) in
      eight western states was mailed a survey. The survey used 5-point Likerttype
      scales to assess the frequency and helpfulness of interactions with community
      pharmacists, as well as level of agreement with specific statements relating to
      pharmacists' current and possible expanded roles. Responses ranged from +2 (very
      frequently/very helpful/strongly agree) to -2 (very infrequently/not helpful at
      all/strongly disagree). RESULTS: 799 analyzable questionnaires were received. On
      average, midlevel providers interacted with pharmacists more frequently (median 
      0.23 and -0.51 for midlevels and physicians, respectively, P < 0.01). The
      helpfulness of interactions was rated positively by both groups, but the median
      rating by midlevel providers was higher compared with physicians (0.86 vs. 0.59,
      P < 0.01). Community pharmacists were rated most favorably on their traditional
      functions, including patient counseling and reporting drug
      allergies/interactions. Results were weakly favorable toward expanded functions,
      such as discussing therapeutic alternatives with patients and dispensing sample
      medications from pharmacies. Both groups agreed that community pharmacists are
      valuable sources of information, with midlevel providers indicating a
      significantly higher level of agreement (1.07 vs. 0.80, P < 0.01). CONCLUSION:
      Most primary care physicians and midlevel providers support the current role of
      community pharmacists. Midlevel providers appeared to interact more frequently
      with pharmacists and indicated higher average helpfulness ratings for
      pharmacists. For pharmaceutical care to be realized in the community setting, a
      concerted effort by the pharmacy profession will be necessary to further
      demonstrate its benefits and feasibility. Midlevel providers may be helpful in
      facilitating this process.

PMID- 19589768
TI  - Identifying patients at risk of cardiovascular disease: a pharmacist-managed
      screening event for union workers and their dependents.
AB  - OBJECTIVE: To describe a pharmacist-managed health screening as a tool to
      identify patients who were at risk for cardiovascular disease (CVD). DESIGN:
      Descriptive nonexperimental study. SETTING: A community pharmacy, a health
      benefit consulting company, and two local unions of plumbers and electricians in
      the Quad Cities area (Mid-Mississippi Valley) in fall 2006. PATIENTS: Union
      members and their dependents who received any one of the following pharmacist
      managed screening services: systolic blood pressure (SBP), diastolic blood
      pressure (DBP), total cholesterol, and high-density lipoprotein (HDL).
      INTERVENTION: Pharmacist-managed CVD risk screening program coordinated by a
      health benefit consulting company. MAIN OUTCOME MEASURES: Risk levels of CVD
      according to SBP, DBP, total cholesterol, and HDL. RESULTS: 452 patients 20 years
      of age or older were screened. A total of 137 participants (45.2%) had an SBP of
      140 mm Hg or more and 73 (24.1%) a DBP of 90 mm Hg or more. Among patients who
      checked their total cholesterol or HDL, 81 (24.0%) had high total cholesterol and
      55 (16.4%) low HDL. CONCLUSION: A pharmacist-managed health screening program was
      a tool to identify patients at risk of CVD. At-risk individuals could be
      potential participants in a cardiovascular risk management service.

PMID- 19589769
TI  - Pharmacists' advancing roles in drug and disease management: a review of states'
      legislation.
AB  - OBJECTIVES: To determine which states in the United States have provisions in
      place for pharmacist participation in drug and disease management programs and/or
      collaborative practice agreements and to provide comparison and discussion
      regarding such provisions. A secondary endpoint was the requirements of
      certification, credentialing, and registration with the specific state's rules
      and regulations. DATA SOURCES: Information was gathered from states' statutes,
      rules, and regulations. Acquisition of each state's laws was achieved through
      various forms of electronic media. Data were accessed from January to March 2008.
      DATA SYNTHESIS: 19 states (38%) had specific provisions for disease management,
      33 (66%) had provisions for drug therapy management, and 37 (74%) had provisions
      for collaborative practice. A total of 11 states (22%) specified that pharmacists
      receive specialized training to participate in such endeavors. Board approval or
      notification for collaborative practice agreements was required in 16 states
      (32%). CONCLUSION: With varying degrees of autonomy and restriction, pharmacists
      in certain states have the ability to develop disease management and/or
      collaborative practice programs. For pharmacists to take advantage of these new
      direct patient care opportunities, knowing the rules and requirements of their
      state's legislation is essential.

PMID- 19589770
TI  - Eugene Gustave Eberle 1863-1942: pharmacy's chronicler.

PMID- 19589771
TI  - Immunizations against bioterrorism: smallpox and anthrax.

PMID- 19589773
TI  - Reducing medication errors, comparative effectiveness, and glucocorticosteroid
      dosing.

PMID- 19589774
TI  - De novo SCN1A mutations in Dravet syndrome and related epileptic encephalopathies
      are largely of paternal origin.
AB  - BACKGROUND: Dravet syndrome is a severe infantile epileptic encephalopathy caused
      in approximately 80% of cases by mutations in the voltage gated sodium channel
      subunit gene SCN1A. The majority of these mutations are de novo. The parental
      origin of de novo mutations varies widely among genetic disorders and the aim of
      this study was to determine this for Dravet syndrome. METHODS: 91 patients with
      de novo SCN1A mutations and their parents were genotyped for single nucleotide
      polymorphisms (SNPs) in the region surrounding their mutation. Allele specific
      polymerase chain reaction (PCR) based on informative SNPs was used to separately
      amplify and sequence the paternal and maternal alleles to determine in which
      parental chromosome the mutation arose. RESULTS: The parental origin of SCN1A
      mutations was established in 44 patients for whom both parents were available and
      SNPs were informative. The mutations were of paternal origin in 33 cases and of
      maternal origin in the remaining 11 cases. De novo mutation of SCN1A most
      commonly, but not exclusively, originates from the paternal chromosome. The
      average age of parents originating mutations did not differ from that of the
      general population. CONCLUSIONS: The greater frequency of paternally derived
      mutations in SCN1A is likely to be due to the greater chance of mutational events
      during the increased number of mitoses which occur during spermatogenesis
      compared to oogenesis, and the greater susceptibility to mutagenesis of the
      methylated DNA characteristic of sperm cells.

PMID- 19589772
TI  - New drugs: golimumab, besifloxacin hydrochloride, and artemether/lumefantrine.

PMID- 19589775
TI  - Subcomplexes of PA700, the 19 S regulator of the 26 S proteasome, reveal relative
      roles of AAA subunits in 26 S proteasome assembly and activation and ATPase
      activity.
AB  - We have identified, purified, and characterized three subcomplexes of PA700, the
      19 S regulatory complex of the 26 S proteasome. These subcomplexes (denoted PS-1,
      PS-2, and PS-3) collectively account for all subunits present in purified PA700
      but contain no overlapping components or significant levels of non-PA700
      proteins. Each subcomplex contained two of the six AAA subunits (Rpt1-6) that
      form the binding interface of PA700 with the 20 S proteasome, the protease
      component of the 26 S proteasome. Unlike intact PA700, no individual PA700
      subcomplex displayed ATPase activity or proteasome activating activity. However,
      both activities were manifested by ATP-dependent in vitro reconstitution of PA700
      from the subcomplexes. We exploited functional reconstitution to define and
      distinguish roles of different PA700 subunits in PA700 function by selective
      alteration of subunits within individual subcomplexes prior to reconstitution.
      Carboxypeptidase treatment of either PS-2 or PS-3, subcomplexes containing
      specific Rpt subunits previously shown to have important roles in 26 S proteasome
      assembly and activation, inhibited these processes but did not affect PA700
      reconstitution or ATPase activity. Thus, the intact C termini of both subunits
      are required for 26 S proteasome assembly and activation but not for PA700
      reconstitution. Surprisingly, carboxypeptidase treatment of PS-1 also inhibited
      26 S proteasome assembly and activation upon reconstitution with untreated PS-2
      and PS-3. These results suggest a previously unidentified role for other PA700
      subunits in 26 S proteasome assembly and activation. Our results reveal relative
      structural and functional relationships among the AAA subunits of PA700 and new
      insights about mechanisms of 26 S proteasome assembly and activation.

PMID- 19589776
TI  - Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and
      RhoA small G proteins at leading edges of moving NIH3T3 cells.
AB  - Cyclical activation and inactivation of Rho family small G proteins, such as Rho,
      Rac, and Cdc42, are needed for moving cells to form leading edge structures in
      response to chemoattractants. However, the mechanisms underlying the dynamic
      regulation of their activities are not fully understood. We recently showed that
      another small G protein, Rap1, plays a crucial role in the platelet-derived
      growth factor (PDGF)-induced formation of leading edge structures and activation
      of Rac1 in NIH3T3 cells. We showed here that knockdown of afadin, an actin
      binding protein, in NIH3T3 cells resulted in a failure to develop leading edge
      structures in association with an impairment of the activation of Rap1 and Rac1
      and inactivation of RhoA in response to PDGF. Overexpression of a constitutively
      active mutant of Rap1 (Rap1-CA) and knockdown of SPA-1, a Rap1 GTPase-activating
      protein that was negatively regulated by afadin by virtue of binding to it, in
      afadin-knockdown NIH3T3 cells restored the formation of leading edge structures
      and the reduction of the PDGF-induced activation of Rac1 and inactivation of
      RhoA, suggesting that the inactivation of Rap1 by SPA-1 is responsible for
      inhibition of the formation of leading edge structures. The effect of Rap1-CA on
      the restoration of the formation of leading edge structures and RhoA inactivation
      was diminished by additional knockdown of ARAP1, a Rap-activated Rho GAP, which
      localized at the leading edges of moving NIH3T3 cells. These results indicate
      that afadin regulates the cyclical activation and inactivation of Rap1, Rac1, and
      RhoA through SPA-1 and ARAP1.

PMID- 19589777
TI  - A conserved Na(+) binding site of the sodium-coupled neutral amino acid
      transporter 2 (SNAT2).
AB  - The SLC38 family of solute transporters mediates the coupled transport of amino
      acids and Na(+) into or out of cells. The structural basis for this coupled
      transport process is not known. Here, a profile-based sequence analysis approach
      was used, predicting a distant relationship with the SLC5/6 transporter families.
      Homology models using the LeuT(Aa) and Mhp1 transporters of known structure as
      templates were established, predicting the location of a conserved Na(+) binding
      site in the center of membrane helices 1 and 8. This homology model was tested
      experimentally in the SLC38 member SNAT2 by analyzing the effect of a mutation to
      Thr-384, which is predicted to be part of this Na(+) binding site. The results
      show that the T384A mutation not only inhibits the anion leak current, which
      requires Na(+) binding to SNAT2, but also dramatically lowers the Na(+) affinity
      of the transporter. This result is consistent with a previous analysis of the
      N82A mutant transporter, which has a similar effect on anion leak current and
      Na(+) binding and which is also expected to form part of the Na(+) binding site.
      In contrast, random mutations to other sites in the transporter had little or no
      effect on Na(+) affinity. Our results are consistent with a cation binding site
      formed by transmembrane helices 1 and 8 that is conserved among the SLC38
      transporters as well as among many other bacterial and plant transporter families
      of unknown structure, which are homologous to SLC38.

PMID- 19589778
TI  - Gln-222 in transmembrane domain 4 and Gln-526 in transmembrane domain 9 are
      critical for substrate recognition in the yeast high affinity glutathione
      transporter, Hgt1p.
AB  - Hgt1p, a member of the oligopeptide transporter family, is a high affinity
      glutathione transporter from the yeast Saccharomyces cerevisiae. We have explored
      the role of polar or charged residues in the putative transmembrane domains of
      Hgt1p to obtain insights into the structural features of Hgt1p that govern its
      substrate specificity. A total of 22 charged and polar residues in the predicted
      transmembrane domains and other conserved regions were subjected to alanine
      mutagenesis. Functional characterization of these 22 mutants identified 11
      mutants which exhibited significant loss in functional activity. All 11 mutants
      except T114A had protein expression levels comparable with wild type, and all
      except E744A were proficient in trafficking to the cell surface. Kinetic analyses
      revealed differential contributions toward the functional activity of Hgt1p by
      these residues and identified Asn-124 in transmembrane domain 1 (TMD1), Gln-222
      in TMD4, Gln-526 in TMD9, and Glu-544, Arg-554, and Lys-562 in the intracellular
      loop region 537-568 containing the highly conserved proline-rich motif to be
      essential for the transport activity of the protein. Furthermore, mutants Q222A
      and Q526A exhibited a nearly 4- and 8-fold increase in the K(m) for glutathione.
      Interestingly, although Gln-222 is widely conserved among other functionally
      characterized oligopeptide transporter family members including those having a
      different substrate specificity, Gln-526 is present only in Hgt1p and Pgt1, the
      only two known high affinity glutathione transporters. These results provide the
      first insights into the substrate recognition residues of a high affinity
      glutathione transporter and on residues/helices involved in substrate
      translocation in the structurally uncharacterized oligopeptide transporter
      family.

PMID- 19589779
TI  - Long range communication between exosites 1 and 2 modulates thrombin function.
AB  - Although exosites 1 and 2 regulate thrombin activity by binding substrates and
      cofactors and by allosterically modulating the active site, it is unclear whether
      there is direct allosteric linkage between the two exosites. To begin to address
      this, we first titrated a thrombin variant fluorescently labeled at exosite 1
      with exosite 2 ligands, HD22 (a DNA aptamer), gamma'-peptide (an analog of the
      COOH terminus of the gamma'-chain of fibrinogen) or heparin. Concentration
      dependent and saturable changes in fluorescence were elicited, supporting inter
      exosite linkage. To explore the functional consequences of this phenomenon, we
      evaluated the capacity of exosite 2 ligands to inhibit thrombin binding to
      gamma(A)/gamma(A)-fibrin, an interaction mediated solely by exosite 1. When
      gamma(A)/gamma(A)-fibrinogen was clotted with thrombin in the presence of HD22,
      gamma'-peptide, or prothrombin fragment 2 there was a dose-dependent and
      saturable decrease in thrombin binding to the resultant fibrin clots.
      Furthermore, HD22 reduced the affinity of thrombin for gamma(A)/gamma(A)-fibrin 6
      fold and accelerated the dissociation of thrombin from preformed
      gamma(A)/gamma(A)-fibrin clots. Similar responses were obtained when surface
      plasmon resonance was used to monitor the interaction of thrombin with
      gamma(A)/gamma(A)-fibrinogen or fibrin. There is bidirectional communication
      between the exosites, because exosite 1 ligands, HD1 (a DNA aptamer) or hirudin
      (54-65) (an analog of the COOH terminus of hirudin), inhibited the exosite 2
      mediated interaction of thrombin with immobilized gamma'-peptide. These findings
      provide evidence for long range allosteric linkage between exosites 1 and 2 on
      thrombin, revealing further complexity to the mechanisms of thrombin regulation.

PMID- 19589780
TI  - Phosphatidylinositol 3-kinase/Akt pathway targets acetylation of Smad3 through
      Smad3/CREB-binding protein interaction: contribution to transforming growth
      factor beta1-induced Epstein-Barr virus reactivation.
AB  - Epstein-Barr virus, a ubiquitous human herpesvirus, is associated with the
      development of carcinomas and lymphomas. We previously showed that transforming
      growth factor beta1 (TGF-beta1) mediated the virus to enter the lytic cycle,
      which is triggered by expression of Z Epstein-Barr virus replication activator
      (ZEBRA), through the ERK 1/2 MAPK signaling pathway. We report here that Akt,
      activated downstream from ERK 1/2, was required for TGF-beta1-induced ZEBRA
      expression and enabled Smad3, a mediator of TGF-beta1 signaling, to be acetylated
      by direct interaction with the co-activator CREB-binding protein and then to
      regulate TGF-beta1-induced ZEBRA expression.

PMID- 19589781
TI  - Nuclear export-independent inhibition of Foxa2 by insulin.
AB  - The Forkhead box A2 transcription factor (Foxa2/HNF-3beta) has been shown to be a
      key regulator of genes involved in the maintenance of glucose and lipid
      homeostasis in the liver. It is constitutively inactivated in several
      hyperinsulinemic/obese mouse models, thereby enhancing their metabolic
      phenotypes. Foxa2 is activated under fasting conditions but is inhibited by
      insulin signaling via phosphatidylinositol 3-kinase/AKT in a phosphorylation
      dependent manner, which results in its nuclear exclusion. However, the mechanism
      and relative importance of its nuclear export has not yet been elucidated. Here
      we show that Foxa2 contains a functional nuclear export signal and is excluded
      from the nucleus via a CRM1-dependent pathway in response to insulin signaling.
      Furthermore, direct evidence is provided that nuclear export-defective Foxa2 is
      phosphorylated and inactivated by insulin in vitro and in vivo. These data
      demonstrate for the first time that phosphorylation itself is the main event
      regulating the activity of Foxa2, suggesting that export-independent mechanisms
      have evolved to ensure inhibition of Foxa2 under conditions in which insulin
      signaling is present.

PMID- 19589782
TI  - Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor
      1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism.
AB  - The hypoxic response in humans is regulated by the hypoxia-inducible
      transcription factor system; inhibition of hypoxia-inducible factor (HIF)
      activity has potential for the treatment of cancer. Chetomin, a member of the
      epidithiodiketopiperazine (ETP) family of natural products, inhibits the
      interaction between HIF-alpha and the transcriptional coactivator p300. Structure
      activity studies employing both natural and synthetic ETP derivatives reveal that
      only the structurally unique ETP core is required and sufficient to block the
      interaction of HIF-1alpha and p300. In support of both cell-based and animal work
      showing that the cytotoxic effect of ETPs is reduced by the addition of Zn(2+)
      through an unknown mechanism, our mechanistic studies reveal that ETPs react with
      p300, causing zinc ion ejection. Cell studies with both natural and synthetic
      ETPs demonstrated a decrease in vascular endothelial growth factor and
      antiproliferative effects that were abrogated by zinc supplementation. The
      results have implications for the design of selective ETPs and for the
      interaction of ETPs with other zinc ion-binding protein targets involved in gene
      expression.

PMID- 19589783
TI  - Cyclosporin A decreases apolipoprotein E secretion from human macrophages via a
      protein phosphatase 2B-dependent and ATP-binding cassette transporter A1 (ABCA1)
      independent pathway.
AB  - Cyclosporin A (CsA) is an immunosuppressant that inhibits protein phosphatase 2B
      (PP2B/calcineurin) and is associated with hyperlipidemia, decreased cholesterol
      efflux via ATP-binding cassette transporter A1 (ABCA1), and increased risk of
      atherosclerosis. Apolipoprotein E (apoE) is an important regulator of lipid
      metabolism and atherosclerosis, the secretion of which from human macrophages is
      regulated by the serine/threonine protein kinase A (PKA) and intracellular
      calcium (Ca(2+)) (Kockx, M., Guo, D. L., Huby, T., Lesnik, P., Kay, J.,
      Sabaretnam, T., Jary, E., Hill, M., Gaus, K., Chapman, J., Stow, J. L., Jessup,
      W., and Kritharides, L. (2007) Circ. Res. 101, 607-616). As PP2B is Ca(2+)
      dependent and has been linked to PKA-dependent processes, we investigated whether
      CsA modulated apoE secretion. CsA dose- and time-dependently inhibited secretion
      of apoE from primary human macrophages and from Chinese hamster ovary cells
      stably transfected with human apoE and increased cellular apoE levels without
      affecting apoE mRNA. [(35)S]Met kinetic modeling studies showed that CsA
      inhibited both secretion and degradation of apoE, increasing the half-life of
      cellular apoE 2-fold. CsA also inhibited secretion from primary human Tangier
      disease macrophages and from mouse macrophages deficient in ABCA1, indicating
      that the effect is independent of the known inhibition of ABCA1 by CsA. The role
      of PP2B in mediating apoE secretion was confirmed using additional peptide and
      chemical inhibitors of PP2B. Importantly, kinetic modeling, live-cell imaging,
      and confocal microscopy all indicated that CsA inhibited apoE secretion by
      mechanisms quite distinct from those of PKA inhibition, most likely inducing
      accumulation of apoE in the endoplasmic reticulum compartment. Taken together,
      these results establish a novel mechanism for the pro-atherosclerotic effects of
      CsA, and establish for the first time a role for PP2B in regulating the
      intracellular transport and secretion of apoE.

PMID- 19589784
TI  - FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.
AB  - FANCI is integral to the Fanconi anemia (FA) pathway of DNA damage repair. Upon
      the occurrence of DNA damage, FANCI becomes monoubiquitinated on Lys-523 and
      relocalizes to chromatin, where it functions with monoubiquitinated FANCD2 to
      facilitate DNA repair. We show that FANCI and its C-terminal fragment possess a
      DNA binding activity that prefers branched structures. We also demonstrate that
      FANCI can be ubiquitinated on Lys-523 by the UBE2T-FANCL pair in vitro. These
      findings should facilitate future efforts directed at elucidating molecular
      aspects of the FA pathway.

PMID- 19589786
TI  - The pattern of excess cancer in dialysis and transplantation.
AB  - BACKGROUND: After transplantation, cancer risk varies from no increase for
      several common cancers to a many-fold increase for a number of, chiefly virus
      associated, cancers. The smaller excess of cancer in dialysis has been less well
      described, but two studies suggested that impaired immunity might be responsible.
      METHODS: In a population-based cohort study of 28 855 patients who received renal
      replacement therapy (RRT), we categorized incident cancers as end-stage kidney
      disease (ESKD) related, immune deficiency related, not related to immune
      deficiency, or of uncertain status, according to whether they were, or were not,
      increased in published reports of cancer in ESKD prior to starting RRT, organ
      transplantation or human immunodeficiency virus infection. Standardized incidence
      ratios for, and excess burdens of, cancer were calculated for all persons
      normally resident in Australia starting treatment by dialysis or renal
      transplantation from 1982 to 2003. RESULTS: The risk for ESKD-related cancers was
      increased 4-fold in dialysis and during transplant function. For immune
      deficiency-related cancers, the increase was 1.5 (95% CI 1.3-1.6) times in
      dialysis, and 5-fold after transplantation. ESKD- or immune deficiency-related
      cancers contributed to approximately 90% of the excess burden of cancer, 48% and
      36%, respectively, in dialysis, and 10% and 78% after transplantation. The
      remaining excess malignancy was contributed by cancers whose relationship with
      ESKD and immune deficiency is not yet certain. CONCLUSIONS: In RRT, the increase
      in cancer is restricted, largely if not wholly, to cancers with origins in ESKD
      or related to immune deficiency. For the former, the cancer risk is similar in
      dialysis and transplantation, but for immune deficiency-related cancers, the
      relative risk is much greater after transplantation.

PMID- 19589787
TI  - Primary focal segmental glomerulosclerosis in adults: is the Indian cohort
      different?
AB  - BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) has been redefined
      into five morphological categories that have different pathogenetic etiologies
      and are expected to have diverse clinical behaviour in terms of presentation,
      remission of proteinuria, progression of the disease and therapeutic response.
      The relative frequency of the variants of FSGS differs in different populations.
      METHODS: A total of 210 cases of adult primary FSGS diagnosed during 4 years (May
      2002 to June 2006) were categorized into the variants and their presentation and
      morphological details were compared. Renal biopsies were studied by light
      microscopy, immunofluorescence/immunohistochemistry and electron microscopy.
      RESULTS: In the present study, the frequency of various morphological variants
      was collapsing 2%, tip 13.5%, cellular variant 8%, perihilar 4% and FSGS-NOS
      72.5%. The variants had a significant difference in the duration of onset of
      illness at the time of biopsy. The cellular variants were biopsied the earliest
      (4.38 +/- 5.57 months) followed by collapsing (10.75 +/- 16.88 months) and
      perihilar variant at a later stages (65.33 +/- 99.30 months). The difference in
      the degree of proteinuria was statistically significant (P = 0.017) amongst
      various variants, being highest in collapsing variant (6.17 +/- 4.67 g/day) and
      lowest in perihilar variant (1.94 +/- 0.94 g/day). CONCLUSION: The present study
      highlights that there is difference in the prevalence and some of the clinical
      parameters at the time of presentation in Indian patients. There was lower
      prevalence of perihilar variant and a higher prevalence of tip and cellular
      variants taken together when compared with the western literature, and this was
      similar to observations of another Asian cohort (China). Collapsing variant was
      infrequent when compared to the west.

PMID- 19589785
TI  - HER2 carboxyl-terminal fragments regulate cell migration and cortactin
      phosphorylation.
AB  - A group of breast cancer patients with a higher probability of developing
      metastasis expresses a series of carboxyl-terminal fragments (CTFs) of the
      tyrosine kinase receptor HER2. One of these fragments, 611-CTF, is a hyperactive
      form of HER2 that constitutively establishes homodimers maintained by disulfide
      bonds, making it an excellent model to study overactivation of HER2 during tumor
      progression and metastasis. Here we show that expression of 611-CTF increases
      cell motility in a variety of assays. Since cell motility is frequently regulated
      by phosphorylation/dephosphorylation, we looked for phosphoproteins mediating the
      effect of 611-CTF using two alternative proteomic approaches, stable isotope
      labeling with amino acids in cell culture and difference gel electrophoresis, and
      found that the latter is particularly well suited to detect changes in
      multiphosphorylated proteins. The difference gel electrophoresis screening
      identified cortactin, a cytoskeleton-binding protein involved in the regulation
      of cell migration, as a phosphoprotein probably regulated by 611-CTF. This result
      was validated by characterizing cortactin in cells expressing this HER2 fragment.
      Finally, we showed that the knockdown of cortactin impairs 611-CTF-induced cell
      migration. These results suggest that cortactin is a target of 611-CTF involved
      in the regulation of cell migration and, thus, in the metastatic behavior of
      breast tumors expressing this CTF.

PMID- 19589788
TI  - Enhanced coronary vascular turgor effect on post-ischemic diastolic function in
      hypertrophied hearts.
AB  - We investigated the effect of coronary perfusion pressure on post-ischemic left
      ventricular (LV) diastolic function in the hypertrophied heart. LV pressure
      overload was induced in four-week-old rats by abdominal aortic constriction (AC),
      with controls (C) undergoing sham operations. At six weeks of age, isolated
      Langendorff-perfused hearts (perfusion pressures: 75 and 110 mmHg in C and AC
      hearts, respectively) were subjected to hypothermic global ischemia (15 degrees
      C, 210 min) followed by 65 min of reperfusion (group I: C hearts subjected to
      aerobic perfusion alone, group II: C hearts subjected to ischemia/reperfusion,
      group III: AC hearts subjected to aerobic perfusion alone, group IV: AC hearts
      subjected to ischemia/reperfusion; n=6/group). LV end-diastolic pressure (LVEDP)
      at a constant balloon volume was assessed under perfusion pressures of 110, 75,
      and 0 mmHg during aerobic perfusion alone (groups I and III) or post-ischemic
      perfusion (groups II and IV). The LVEDP differences between perfusion pressures
      of 75 and 110 mmHg were 6.2+/-3.2, 3.2+/-2.7, 3.2+/-1.5, and 12.8+/-4.2* mmHg in
      groups I, II, III, and IV, respectively (*P<0.05 vs. group III). Pressure
      overload-induced hypertrophied hearts exhibit post-ischemic diastolic
      dysfunction, which may be caused partly by the enhanced coronary vascular turgor
      effect on myocardial stiffness.

PMID- 19589789
TI  - Total aortic arch stenting--hemodynamical impact of carotid artery perfusion.
AB  - The aim of this experimental study is to evaluate the feasibility and the outcome
      of total endovascular stent implantation in the aortic arch. Indications for this
      operation-technique would be acute or chronic dissection of the aortic arch (non
      A-non-B dissection) or type B dissection with retrograde extension. Four pigs
      were canulated via the distal abdominal aorta and a retrograde placement of a
      Djumbodis arch stent (4-9 cm) was controlled by using intravascular ultrasound
      and intracardiac ultrasound by the inferior cava vein and under radioscopic
      control. Cerebral perfusion, by using a flow meter placed on one prepared carotid
      artery, were controlled before, immediate post-procedural (<1 min), and in the
      early follow-up after aortic arch stent implantation. During the implantation
      process, especially during balloon inflation and deflation, mean carotid
      perfusion decreases slightly. A reactive increase of carotid perfusion after
      stent placements indicates transitory cerebral hypo-perfusion. Non-covered aortic
      arch stent implantation is technically feasible and could be a potential
      treatment option in otherwise inoperable arch dissections. The time required for
      balloon inflation and deflation causes an important risk of cerebral ischemia.
      The latter can be reduced by transaxillary perfusion.

PMID- 19589790
TI  - Recurrent dedifferentiated liposarcoma of mediastinum involving lung and pleura.
AB  - We report a case of primary recurrent mediastinal dedifferentiated liposarcoma
      with unusual long-term survival. A woman who complained of dyspnea showed on
      imaging features a bulky posterior mediastinal mass which was completely excised
      and initially misdiagnosed as an angiomyolipoma. She recurred 15 months later and
      histological examination showed a dedifferentiated liposarcoma. Resection was
      incomplete and the patient received adjuvant therapy. Eight years later a second
      recurrence occurred in the right pleura and lung. The patient died three months
      later.

PMID- 19589791
TI  - Primary endobronchial non-Hodgkin lymphoma in an 80-year-old patient with
      prostate cancer.
AB  - The identification of a primary endobronchial non-Hodgkin lymphoma (NHL) is rare.
      We hereby present the case of a primary solitary endobronchial NHL lesion in an
      80-year-old patient with prostate cancer who did not present any systemic
      involvement at the time of diagnosis.

PMID- 19589792
TI  - Transoesophageal electrophysiology study for children: can we swallow the
      limitations?

PMID- 19589793
TI  - Non-ischaemic titrated cardiac injury caused by radiofrequency catheter ablation
      of atrial fibrillation mobilizes CD34-positive mononuclear cells by non-stromal
      cell-derived factor-1alpha mechanism.
AB  - AIMS: It has been known that myocardial ischaemia mobilizes CD34+ bone marrow
      derived cells by the stromal cell-derived factor (SDF)-1alpha pathway. We
      hypothesized that non-ischaemic titrated cardiac injury caused by radiofrequency
      catheter ablation (RFCA) of atrial fibrillation (AF) recruits CD34+ cells by an
      alternative mechanism. METHODS AND RESULTS: Fifty-six patients (39 males, 53.0 +/
      13.5 years old) who underwent electrophysiology study (EPS; n = 10) or RFCA of
      AF (n = 46) were included. Peripheral blood CD34+ cell count and multiple
      serologic markers were evaluated before, immediately after, at 24 h, and 10 days
      after the procedure. The results are as follows: (i) the per cent increase in
      CD34+ cells (%DeltaCD34+) was significant after RFCA compared with after EPS (P <
      0.01), and correlated with RF duration and troponin I, respectively. (ii) In
      contrast, SDF-1alpha decreased after RFCA and had no correlation with %DeltaCD34+
      cells while matrix metalloproteinase (MMP)-9 (P < 0.0001) and GRObeta (P < 0.001)
      increased after RFCA and had correlations with 24 h %DeltaCD34+ cells.
      CONCLUSION: Non-ischaemic titrated cardiac injury caused by AF ablation mobilizes
      CD34+ cells to the peripheral blood through a non-SDF-1alpha pathway associated
      with MMP-9 and GRObeta.

PMID- 19589794
TI  - Atrial antitachycardia pacing: do we still need to talk about it?

PMID- 19589795
TI  - Electrophysiological findings in patients with isolated left ventricular non
      compaction.
AB  - AIMS: Patients with isolated left ventricular non-compaction (IVNC) are at high
      risk for developing ventricular tachyarrhythmias. However, no analysis of
      invasive electrophysiological (EP) findings in these patients has yet been
      performed. METHODS AND RESULTS: We performed a retrospective analysis of EP
      findings in 24 patients with IVNC. Ventricular tachyarrhythmias were inducible in
      nine patients; of these, two patients had sustained monomorphic ventricular
      tachycardia (VT) and two patients had ventricular fibrillation. No specific
      electrocardiographic or echocardiographic finding was predictive of VT
      inducibility. Three of the 9 patients with inducible VT experienced ventricular
      tachyarrhythmias during the follow-up of 61.4+/-50 months, whereas no
      tachyarrhythmias or sudden deaths were noted in 12 patients without inducible VT
      during the follow-up of 30+/-19 months (3 patients in the latter group were lost
      to follow-up). Supraventricular tachyarrhythmias were inducible in seven
      patients. CONCLUSION: Our present study provides the first comprehensive analysis
      of EP findings in patients with IVNC. Ventricular and supraventricular
      arrhythmias can readily be induced in these patients, whereas the inducibility of
      a sustained monomorphic VT is relatively low. Further studies including long-term
      follow-up are required to investigate the role of EP testing for arrhythmic risk
      stratification in these patients.

PMID- 19589796
TI  - Response to intravenous ajmaline: a retrospective analysis of 677 ajmaline
      challenges.
AB  - AIMS: The diagnostic type I ECG in Brugada syndrome (BS) is often concealed and
      fluctuates between the diagnostic and non-diagnostic pattern. Challenge with
      intravenous ajmaline is used to unmask the diagnostic Brugada ECG. The aim of
      this study was to evaluate the safety of the test and to identify predictors for
      the response to an intravenous ajmaline challenge. METHODS AND RESULTS: In four
      tertiary referral centres, 677 consecutive patients underwent an intravenous
      ajmaline challenge for diagnosis or exclusion of BS in accordance with the
      recommendations of the Brugada consensus conferences. Two hundred and sixty-two
      ajmaline challenges (39%) were positive. Male gender, familial BS, sudden cardiac
      arrest (SCA), first-degree AV-block, basal saddleback type ECG, and basal right
      bundle branch block were identified as predictors for a positive ajmaline
      challenge. A predictor for negative ajmaline test was the absence of ST-segment
      elevation at baseline. Six of 12 patients who had experienced SCA, and five of 25
      patients with a familial sudden death exhibited a positive response to ajmaline.
      Only one patient (0.15%) developed sustained ventricular tachyarrhythmias
      (ventricular fibrillation) during ajmaline challenge, which was terminated by a
      single external defibrillator shock. CONCLUSION: Ajmaline challenge is a safe
      procedure to unmask the electrocardiographic pattern of BS. Electrocardiographic
      and clinical parameters were identified to predict patients' response to
      ajmaline. The results of this study guide the clinician in which setting an
      ajmaline challenge is an appropriate diagnostic step.

PMID- 19589797
TI  - Renal insufficiency after cardiac surgery: a challenging clinical problem.

PMID- 19589798
TI  - Prevalence and outcome of newly detected diabetes in patients who undergo
      percutaneous coronary intervention.
AB  - AIMS: The beneficial effect of specific measures in patients with newly detected
      diabetes during percutaneous coronary intervention (PCI) has been poorly studied.
      Here, we determined the prevalence of newly detected diabetes in a cohort of
      patients who underwent PCI and analysed their clinical outcome. METHODS AND
      RESULTS: A prospective study included patients without previous diagnosis of
      diabetes that were referred for PCI between November 2005 and May 2006. Major
      cardiac events were registered after admission and during 12 months of follow-up,
      and oral glucose tolerance was tested at 15 days after hospital discharge. Six
      hundred and sixty-two consecutive patients were referred to our hospital for PCI.
      The distribution of the glycometabolic state of the entire population was (95%
      CI): known diabetes 28.8% (25.2-32.6), newly detected diabetes 16.2% (13.1-19.8),
      impaired glucose tolerance 24.5% (20.8-28.5), impaired fasting glucose 1% (0.4
      2.4), and normal glucose regulation 29.5% (25.5-33.7). In a multivariable
      analysis, the presence of newly detected diabetes was not an independent
      predictor of cardiac events after 1 year of follow-up. CONCLUSION: The prevalence
      of diabetes in patients who underwent PCI was very high (45%), 35% of which was
      patients with newly detected diabetes. In our series newly detected diabetes was
      not an independent predictor of outcome at 12 months. Nevertheless, this finding
      requires independent confirmation in other series to draw general conclusions on
      the whole spectrum of percutaneous interventions.

PMID- 19589799
TI  - The evolution of a UK regional tobacco control office in its early years: social
      contexts and policy dynamics.
AB  - The Smoke Free North East Office (SFNEO) is the first dedicated tobacco control
      office in the UK coordinating a regional tobacco control network, Smoke Free
      North East (SFNE). On the basis of ethnographic research conducted between 2006
      and 2008, this article examines the context for SFNEO's emergence at this time
      and in this region of England, and the main policy and practice challenges it has
      faced in its early years. SFNE formed in a favourable political and cultural
      climate, although regional champions were crucial in setting it up. It has worked
      well in branding itself and in taking advantage of the opportunity to lobby in
      support of comprehensive smoke-free legislation, although the success of the
      legislation presents a risk that people will regard SFNE's work as finished.
      There is a need for independent sustainable funding, strong partnership working
      and the 'bringing together' of existing organizations under its leadership for an
      organization such as SFNE to succeed. SFNE offers a model that is transferable to
      other places as well as to other public health concerns such as alcohol, and has
      been taken up by public health planners and policy makers with alacrity. This
      indicates a general perception that SFNE plays an effective role in public health
      delivery.

PMID- 19589800
TI  - Effects of childhood obesity on hospital care and costs, 1999-2005.
AB  - Childhood obesity is increasingly recognized as an epidemic, but the economic
      consequences have not been well quantified. We evaluated trends in obesity
      associated hospitalizations, charges, and costs using 1999-2005 data from a
      nationally representative sample of admissions to U.S. hospitals. We detected a
      near-doubling in hospitalizations with a diagnosis of obesity between 1999 and
      2005 and an increase in costs from $125.9 million to 237.6 million (in 2005
      dollars) between 2001 and 2005. Medicaid appears to bear a large burden of
      hospitalizations for conditions that occur along with obesity, while private
      payers pay a greater portion of hospitalization costs to treat obesity itself.

PMID- 19589801
TI  - The complex interrelationship between ethnic and socio-economic inequalities in
      health.

PMID- 19589802
TI  - Evaluation of the impact of a health forecast alert service on admissions for
      chronic obstructive pulmonary disease in Bradford and Airedale.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations are
      associated with adverse weather conditions. We examined if a forecasting alert
      service available to general practices in Bradford and Airedale for the winter of
      2007-08 reduced COPD admissions. METHODS: We compared admissions in 2007-08 with
      2006-07 when the service was not available. We examined admissions in December to
      March, and in the 7- and 14-day post-alert periods. There were five alerts in
      2006-07 and four in 2007-08. We compared practices using the service to varying
      extents with practices not using it. RESULTS: Admission rate ratios for practices
      using the service were 0.98 [95% confidence interval (CI): 0.78-1.22] for
      December to March, and 0.82 (CI: 0.57-1.18) and 0.95 (CI: 0.72-1.26) for the 7-
      and 14-day post-alert periods, respectively. When we took into account the
      proportion of patients entered on the alerts system and the duration for which
      practices participated in the service, admission rate ratios for practices fully
      using the service were 1.11 (CI: 0.80-1.52), 1.22 (CI: 0.73-2.04) and 1.21 (CI:
      0.82-1.78) for the three corresponding periods. CONCLUSION: We failed to show
      that any change in admissions associated with the forecasting service was
      significant. More research on the effectiveness of the COPD forecasting service
      is needed.

PMID- 19589803
TI  - The new science of cultural epidemiology to tackle ethnic health inequalities.

PMID- 19589804
TI  - Determination of the target nucleosides for members of two families of 16S rRNA
      methyltransferases that confer resistance to partially overlapping groups of
      aminoglycoside antibiotics.
AB  - The 16S ribosomal RNA methyltransferase enzymes that modify nucleosides in the
      drug binding site to provide self-resistance in aminoglycoside-producing micro
      organisms have been proposed to comprise two distinct groups of S-adenosyl-l
      methionine (SAM)-dependent RNA enzymes, namely the Kgm and Kam families. Here,
      the nucleoside methylation sites for three Kgm family methyltransferases, Sgm
      from Micromonospora zionensis, GrmA from Micromonospora echinospora and Krm from
      Frankia sp. Ccl3, were experimentally determined as G1405 by MALDI-ToF mass
      spectrometry. These results significantly extend the list of securely
      characterized G1405 modifying enzymes and experimentally validate their grouping
      into a single enzyme family. Heterologous expression of the KamB
      methyltransferase from Streptoalloteichus tenebrarius experimentally confirmed
      the requirement for an additional 60 amino acids on the deduced KamB N-terminus
      to produce an active methyltransferase acting at A1408, as previously suggested
      by an in silico analysis. Finally, the modifications at G1405 and A1408, were
      shown to confer partially overlapping but distinct resistance profiles in
      Escherichia coli. Collectively, these data provide a more secure and systematic
      basis for classification of new aminoglycoside resistance methyltransferases from
      producers and pathogenic bacteria on the basis of their sequences and resistance
      profiles.

PMID- 19589805
TI  - Detection of genomic islands via segmental genome heterogeneity.
AB  - While the recognition of genomic islands can be a powerful mechanism for
      identifying genes that distinguish related bacteria, few methods have been
      developed to identify them specifically. Rather, identification of islands often
      begins with cataloging individual genes likely to have been recently introduced
      into the genome; regions with many putative alien genes are then examined for
      other features suggestive of recent acquisition of a large genomic region. When
      few phylogenetic relatives are available, the identification of alien genes
      relies on their atypical features relative to the bulk of the genes in the
      genome. The weakness of these 'bottom-up' approaches lies in the difficulty in
      identifying robustly those genes which are atypical, or phylogenetically
      restricted, due to recent foreign ancestry. Herein, we apply an alternative 'top
      down' approach where bacterial genomes are recursively divided into progressively
      smaller regions, each with uniform composition. In this way, large chromosomal
      regions with atypical features are identified with high confidence due to the
      simultaneous analysis of multiple genes. This approach is based on a generalized
      divergence measure to quantify the compositional difference between segments in a
      hypothesis-testing framework. We tested the proposed genome island prediction
      algorithm on both artificial chimeric genomes and genuine bacterial genomes.

PMID- 19589807
TI  - High-throughput detection and multiplex identification of cell contaminations.
AB  - Unnoticed cell culture contamination by viruses, Mycoplasma, or other cell lines
      is not uncommon and a threat to laboratory safety and the quality of scientific
      results. We developed and validated a novel high-throughput Multiplex cell
      Contamination Test (McCT), which is currently able to detect 37 contamination
      markers in a single reaction. The assay is based on multiplex PCR with target
      specific primers and subsequent hybridization of amplimers to specific
      oligonucleotide probes. McCT proved to be highly specific, sensitive and robust,
      and allows to analyze more than 1000 cell lysates per week. In conclusion, the
      novel McCT assay is a powerful high-throughput tool in assessing cell line
      purity.

PMID- 19589806
TI  - Mechanistic studies of the modulation of cleavage activity of topoisomerase I by
      DNA adducts of mono- and bi-functional PtII complexes.
AB  - Using electrophoresis and replication mapping, we show that the presence of DNA
      adducts of bifunctional antitumor cisplatin or monodentate [PtCl(dien)]Cl (dien =
      diethylenetriamine) in the substrate DNA inhibits eukaryotic topoisomerase 1
      (top1) action, the adducts of cisplatin being more effective. The presence of
      camptothecin in the samples of platinated DNA markedly enhances effects of Pt-DNA
      adducts on top1 activity. Interestingly, the effects of Pt-DNA adducts on the
      catalytic activity of top1 in the presence of camptothecin differ depending on
      the sequence context. A multiple metallation of the short nucleotide sequences on
      the scissile strand, immediately downstream of the cleavage site impedes the
      cleavage by top1. On the other hand, DNA cleavage by top1 at some cleavage sites
      which were not platinated in their close proximity is notably enhanced as a
      consequence of global platination of DNA. We suggest that this enhancement of DNA
      cleavage by top1 may consist in its inability to bind to other cleavage sites
      platinated in their close neighborhood; thus, more molecules of top1 may become
      available for cleavage at the sites where top1 normally cleaves and where
      platination does not interfere.

PMID- 19589808
TI  - Born in Bradford: Madonna and child or?

PMID- 19589811
TI  - Unilateral breast oedema in a case of non-rheumatic giant left atrium.
AB  - Giant left atrium (GLA) is a well-described entity in association with rheumatic
      heart disease. However, mitral valve prolapse is an extremely unusual cause of
      GLA, especially without the compressive symptoms it can often accompany. We
      discuss a case of a 78-year-old lady with no prior history of rheumatic heart
      disease with these findings with the unusual presentation of accompanied
      unilateral breast oedema as a manifestation of heart failure. This case
      illustrates the investigations and treatment options for GLA and the need for
      prompt assessment as it increases the risk of sudden death; therefore, its
      presence warrants careful evaluation and surgical intervention when appropriate.

PMID- 19589812
TI  - The threshold for sensing airflow resistance during tidal breathing rises in old
      age: implications for elderly patients with obstructive airways diseases.
AB  - OBJECTIVE: to determine whether the ability of elderly subjects to detect a rise
      in airflow resistance is attenuated in old age, and to measure the magnitude and
      variability of such a change. METHODS: we studied 124 healthy adults aged 20-86
      years. Progressive external airflow resistance loading was used to measure the
      inspiratory and expiratory load detection thresholds (LDTs) during tidal
      breathing at rest. RESULTS: the mean inspiratory LDT rose from 4.00 (3.06 SD)
      kPa.s/L in the 20-39 age group to 6.51 (6.20) in the 40-64 age group (NS) and
      29.10 (13.58) in the 65 + age group (P < 0.00001). The inspiratory LDT was
      significantly correlated with age, mainly due to the higher thresholds in people
      over the age of 65 (r = 0.7860, P < 0.00001), but did not correlate with age
      corrected forced vital capacity or respiratory rate. Expiratory LDT values and
      correlations were very similar. Day-to-day variability in LDTs tended to be
      higher in older subjects. CONCLUSION: the threshold for detecting external
      resistive loads during tidal breathing rises in old age. This appears to be a
      consequence of ageing processes rather than pathology, and might be a
      manifestation of a fall in proprioceptive acuity in elderly people. This finding
      has clinical implications for the self-management of asthma in old age. There is
      a need to conduct a similar study in patients with airways disease.

PMID- 19589809
TI  - Environmental risk factors for lung cancer in Iran: a case-control study.
AB  - BACKGROUND: Lung cancer remains the leading cause of cancer death in the world.
      In Iran, lung cancer is one of the five leading tumours and its incidence has
      been increasing steadily in both men and women. There is a paucity of data from
      Iran on risk factors for lung cancer. We evaluated environmental risk factors for
      lung cancer in a case-control study in five hospitals of Tehran. METHODS: Between
      October 2002 and October 2005, 242 (178 male, 64 female) patients with
      histologically confirmed lung cancer and two controls for each patient (242
      hospital controls and 242 visiting healthy controls) matched for age, sex and
      place of residence were interviewed using a structured questionnaire on potential
      risk factors for lung cancer, including environmental and occupational exposures.
      Associations between risk factors and lung cancer were assessed using conditional
      logistic regression. RESULTS: Smokers were 66.5% of all cases (85.4% of men and
      14.1% of women) and smoking was the strongest correlate of lung cancer in
      multivariate analysis [odds ratio (OR) 5.4, 95% confidence interval (CI) 3.2
      8.9]. Occupational exposures to inorganic dusts (OR 4.2, 95% CI 2.8-6.7),
      chemical compounds (OR = 3.4, 95% CI 2.1-5.6) and heavy metals (OR 3.0, 95% CI
      1.3-7.0) were also independent risk factors for lung cancer. CONCLUSIONS: In our
      study, smoking was the principal risk factor for lung cancer. However,
      preventable exposures in the environment, including occupational settings, should
      not be ignored.

PMID- 19589810
TI  - Pharmacodynamics of moxifloxacin against a high inoculum of Escherichia coli in
      an in vitro infection model.
AB  - OBJECTIVES: Escherichia coli is the leading bacterial species implicated in intra
      abdominal infections. In these infections a high bacterial burden with pre
      existing resistant mutants are likely to be encountered and resistance could be
      amplified with suboptimal dosing. Our objective was to investigate the
      pharmacodynamics of moxifloxacin against a high inoculum of E. coli using an in
      vitro hollow fibre infection model (HFIM). METHODS: Three wild-type strains of E.
      coli (ATCC 25922, MG1655 and EC28044) were studied by exposing approximately 2 x
      10(8) cfu/mL (20 mL) to escalating dosing regimens of moxifloxacin (ranging from
      30 to 400 mg, once daily). Serial samples were obtained from HFIM over 120 h to
      enumerate the total and resistant subpopulation. Quinolone resistance-determining
      regions of gyrA and parC of resistant isolates were sequenced to confirm the
      mechanism of resistance. RESULTS: The pre-exposure MIC of the three wild-type
      strains was 0.0625 mg/L. Simulated moxifloxacin concentration profiles in HFIM
      were satisfactory (r(2) >or= 0.94). Placebo experiments revealed natural mutants,
      but no resistance amplification. Regrowth and resistance amplification was
      observed between 30 mg/day (AUC/MIC = 47) and 80 mg/day dose (AUC/MIC = 117).
      Sustained bacterial suppression was achieved at >or=120 mg/day dose (AUC/MIC =
      180). Point mutations in gyrA (D87G or S83L) were detected in resistant isolates.
      CONCLUSIONS: Our results suggest that suboptimal dosing may facilitate resistance
      amplification in a high inoculum of E. coli. The clinical dose of moxifloxacin
      (400 mg/day) was adequate to suppress resistance development in three wild-type
      strains. Clinical relevance of these findings warrants further in vivo
      investigation.

PMID- 19589813
TI  - Influence of occupational stress on mental health among Chinese off-shore oil
      workers.
AB  - AIM: To explore the influence of occupational stress on mental health in off
      shore oil production. METHODS: A cross-sectional survey was conducted among 561
      Chinese off-shore oil workers. The workers were invited to fill in a self
      administered questionnaire exploring their socio-demographic characteristics,
      occupational stress levels, and 12-item general health questionnaire. A
      hierarchical multiple regression procedure was used to assess the effects of
      occupational stress on mental health. RESULTS: After controlling for age,
      educational level, marital status and years of off-shore work, poor mental health
      was found to have a significant positive association with seven of the nine
      identified sources of occupational stress. They were: conflict between job and
      family/social life, poor development of career and achievement at work, safety
      problems at work, management problems and poor relationship with others at work,
      poor physical environment of the work place, uncomfortable ergonomic factors at
      work, and poor organizational structure at work. All of these occupational stress
      sources together explained 19.9% of the total variance. CONCLUSIONS: The results
      confirmed that occupational stress was a major risk factor for poor mental health
      among Chinese off-shore oil workers. Reducing or eliminating occupational
      stressors at work would benefit workers' mental health.

PMID- 19589814
TI  - Gene defects and allergy.

PMID- 19589815
TI  - Reducing pregnancy and health risk behaviours in teenagers.

PMID- 19589817
TI  - Libel law in the UK.

PMID- 19589816
TI  - Filaggrin gene defects and risk of developing allergic sensitisation and allergic
      disorders: systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate whether filaggrin gene defects, present in up to one in
      10 western Europeans and North Americans, increase the risk of developing
      allergic sensitisation and allergic disorders. DESIGN: Systematic review and meta
      analysis. DATA SOURCES: Medline, Embase, ISI Science Citation Index, BIOSIS, ISI
      Web of Knowledge, UK National Research Register, clinical trials.gov, the Index
      to Theses and Digital dissertations, and grey literature using OpenSIGLE. STUDY
      SELECTION: Genetic epidemiological studies (family, case-control) of the
      association between filaggrin gene defects and allergic sensitisation or allergic
      disorders. DATA EXTRACTION: Atopic eczema or dermatitis, food allergy, asthma,
      allergic rhinitis, and anaphylaxis, along with relevant immunological variables
      relating to the risk of allergic sensitisation as assessed by either positive
      skin prick testing or increased levels of allergen specific IgE. DATA SYNTHESIS:
      24 studies were included. The odds of developing allergic sensitisation was 1.91
      (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to
      2.07) in the case-control studies. The odds of developing atopic eczema was 1.99
      (1.72 to 2.31) in the family studies and 4.78 (3.31 to 6.92) in the case-control
      studies. Three studies investigated the association between filaggrin gene
      mutations and allergic rhinitis in people without atopic eczema: overall odds
      ratio 1.78 (1.16 to 2.73). The four studies that investigated the association
      between filaggrin gene mutations and allergic rhinitis in people with atopic
      eczema reported a significant association: pooled odds ratio from case-control
      studies 2.84 (2.08 to 3.88). An overall odds ratio for the association between
      filaggrin gene mutations and asthma in people with atopic eczema was 2.79 (1.77
      to 4.41) in case-control studies and 2.30 (1.66 to 3.18) in family studies. None
      of the studies that investigated filaggrin gene mutations and asthma in people
      without atopic eczema reported a significant association; overall odds ratio was
      1.30 (0.7 to 2.30) in the case-control studies. The funnel plots suggested that
      publication bias was unlikely to be an explanation for these findings. No studies
      investigated the association between filaggrin gene mutations and food allergy or
      anaphylaxis. CONCLUSIONS: Filaggrin gene defects increase the risk of developing
      allergic sensitisation, atopic eczema, and allergic rhinitis. Evidence of the
      relation between filaggrin gene mutations and atopic eczema was strong, with
      people manifesting increased severity and persistence of disease. Filaggrin gene
      mutations also increased the risk of asthma in people with atopic eczema.
      Restoring skin barrier function in filaggrin deficient people in early life may
      help prevent the development of sensitisation and halt the development and
      progression of allergic disease.

PMID- 19589818
TI  - Chiropractic for paediatric conditions: substantial evidence?

PMID- 19589820
TI  - Overdiagnosis and mammography screening.

PMID- 19589821
TI  - Overdiagnosis in publicly organised mammography screening programmes: systematic
      review of incidence trends.
AB  - OBJECTIVE: To estimate the extent of overdiagnosis (the detection of cancers that
      will not cause death or symptoms) in publicly organised screening programmes.
      DESIGN: Systematic review of published trends in incidence of breast cancer
      before and after the introduction of mammography screening. DATA SOURCES: PubMed
      (April 2007), reference lists, and authors. Review methods One author extracted
      data on incidence of breast cancer (including carcinoma in situ), population
      size, screening uptake, time periods, and age groups, which were checked
      independently by the other author. Linear regression was used to estimate trends
      in incidence before and after the introduction of screening and in older,
      previously screened women. Meta-analysis was used to estimate the extent of
      overdiagnosis. RESULTS: Incidence data covering at least seven years before
      screening and seven years after screening had been fully implemented, and
      including both screened and non-screened age groups, were available from the
      United Kingdom; Manitoba, Canada; New South Wales, Australia; Sweden; and parts
      of Norway. The implementation phase with its prevalence peak was excluded and
      adjustment made for changing background incidence and compensatory drops in
      incidence among older, previously screened women. Overdiagnosis was estimated at
      52% (95% confidence interval 46% to 58%). Data from three countries showed a drop
      in incidence as the women exceeded the age limit for screening, but the reduction
      was small and the estimate of overdiagnosis was compensated for in this review.
      CONCLUSIONS: The increase in incidence of breast cancer was closely related to
      the introduction of screening and little of this increase was compensated for by
      a drop in incidence of breast cancer in previously screened women. One in three
      breast cancers detected in a population offered organised screening is
      overdiagnosed.

PMID- 19589823
TI  - WHO researchers start trial on a new drug for river blindness.

PMID- 19589822
TI  - Effect of unsupervised home based proprioceptive training on recurrences of ankle
      sprain: randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of an unsupervised proprioceptive
      training programme on recurrences of ankle sprain after usual care in athletes
      who had sustained an acute sports related injury to the lateral ankle ligament.
      DESIGN: Randomised controlled trial, with one year follow-up. SETTING: Primary
      care. PARTICIPANTS: 522 athletes, aged 12-70, who had sustained a lateral ankle
      sprain up to two months before inclusion; 256 (120 female and 136 male) in the
      intervention group; 266 (128 female and 138 male) in the control group.
      INTERVENTION: Both groups received treatment according to usual care. Athletes
      allocated to the intervention group additionally received an eight week home
      based proprioceptive training programme. MAIN OUTCOME MEASURE: Self reported
      recurrence of ankle sprain. RESULTS: During the one year follow-up, 145 athletes
      reported a recurrent ankle sprain: 56 (22%) in the intervention group and 89
      (33%) in the control group. Nine athletes needed to be treated to prevent one
      recurrence (number needed to treat). The intervention programme was associated
      with a 35% reduction in risk of recurrence. Cox regression analysis showed
      significantly fewer recurrent ankle sprains in the intervention than in the
      control group. This effect was found for self reported recurrent ankle sprains
      (relative risk 0.63, 95% confidence interval 0.45 to 0.88), recurrent ankle
      sprains leading to loss of sports time (0.53, 0.32 to 0.88), and recurrent ankle
      sprains resulting in healthcare costs or lost productivity costs (0.25, 0.12 to
      0.50). No significant differences were found between medically treated athletes
      in the intervention group and medically treated controls. Athletes in the
      intervention group who were not medically treated had a significantly lower risk
      of recurrence than controls who were not medically treated. CONCLUSIONS: The use
      of a proprioceptive training programme after usual care of an ankle sprain is
      effective for the prevention of self reported recurrences. This proprioceptive
      training was specifically beneficial in athletes whose original sprain was not
      medically treated. TRIAL REGISTRATION: ISTRCN34177180.

PMID- 19589824
TI  - Life expectancy in England between the rich and poor widens for both men and
      women.

PMID- 19589825
TI  - Researchers create human sperm using embryonic stem cells.

PMID- 19589826
TI  - House of Lords votes against immunity from prosecution for relatives who help in
      assisted suicide abroad.

PMID- 19589827
TI  - WHO to call on nations with high rates of swine flu to move away from testing all
      suspected cases.

PMID- 19589828
TI  - Role of the endocannabinoid system in ethanol-induced inhibition of salivary
      secretion.
AB  - AIM: The aim of the present study was to determine whether the endocannabinoid
      system could be involved in the ethanol-induced inhibition of salivation in adult
      male Wistar rats. METHODS: Salivary secretion induced by different concentrations
      of methacholine, a cholinergic agonist, and the endocannabinoid arachidonoyl
      ethanolamide (anandamide, AEA) production in the submandibular gland (SMG) were
      determined in rats after ethanol (3 g/kg) administration by gastric gavage. To
      study the participation of cannabinod receptors in ethanol action, we evaluated
      methacholine-induced salivary secretion after ethanol administration when CB1 or
      CB2 receptors were blocked by intra-SMG injections of their selective antagonists
      AM251 and AM630, respectively. Additionally, we evaluated the in vitro effect of
      ethanol (0.1 M) on SMG production of cAMP, alone or combined with AM251 or AM630.
      RESULTS: Acute ethanol administration increased AEA production in SMG and also
      inhibited the methacholine-induced saliva secretion that was partially restored
      by intraglandular injection of AM251 or AM630. In addition, ethanol significantly
      reduced the forskolin-induced increase in cAMP content in SMG in vitro while
      treatment with AM251 blocked this response. CONCLUSION: We conclude that the
      inhibitory effect produced by ethanol on submandibular gland salivary secretion
      is mediated, at least in part, by the endocannabinoid system.

PMID- 19589829
TI  - Expression of the Streptococcus mutans essential two-component regulatory system
      VicRK is pH and growth-phase dependent and controlled by the LiaFSR three
      component regulatory system.
AB  - As an inhabitant of the human oral cavity, Streptococcus mutans faces frequent
      environmental changes. Two-component regulatory systems (TCSs) play a critical
      role in responding to these changes. Recently, an essential TCS, VicRKX, has been
      identified. The objective of this study was to identify the environmental signal
      and bacterial factors regulating the expression of the vicRKX operon. The
      promoter of the vicRKX operon was fused to a promoterless lacZ reporter gene and
      introduced into S. mutans UA159. LacZ plate assay identified pH, vancomycin,
      ampicillin, penicillin G and polymyxin B, but not carbohydrates, as factors
      affecting expression. Using RNA dot-blotting, high levels of vicR transcript were
      observed in cells at the mid- and late-exponential phase of growth and in cells
      grown in media buffered at pH 7.8. Given that vicR expression was pH-dependent,
      the genes encoding a putative pH-sensing three-component regulatory system
      (LiaFSR) were deleted. The liaS mutant exhibited upregulation of vicR regardless
      of the growth condition. The role of VicK, VicX, and the competence-signal
      peptide (CSP) was also investigated; the results showed that vicR expression was
      not autoregulated and was downregulated by the CSP in a ComX-independent manner.
      In conclusion, the expression of vicRKX is influenced by culture pH, growth phase
      and antibiotic stress, and is regulated by LiaFRS.

PMID- 19589831
TI  - A peroxiredoxin from Mycoplasma hyopneumoniae with a possible role in H2O2
      detoxification.
AB  - Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia,
      which affects pig farms worldwide, causing heavy economic losses. In the
      infection process, this bacterium is exposed to reactive oxygen species (ROS)
      from its own metabolism or generated by the host as one of the strategies used to
      neutralize the pathogen. Although the presence of classical antioxidant enzymes
      would be expected in M. hyopneumoniae, important genes directly related to
      protection against ROS, such as superoxide dismutase, catalases and glutathione
      peroxidase, have not been identified by sequence homology in the genome sequence
      annotation. Among the few identified M. hyopneumoniae genes coding for proteins
      possibly involved with suppression of ROS-mediated damage, one (tpx) coding for a
      peroxiredoxin (MhPrx) has been recognized. The sequence and phylogenetic analyses
      perfomed in this study indicate that MhPrx is closely related to the atypical 2
      Cys peroxiredoxin subfamily, although it has only one cysteine in its sequence.
      The MhPrx coding DNA sequence was cloned and expressed in Escherichia coli to
      produce a recombinant MhPrx (rMhPrx), which was purified and used to immunize
      mice and produce an anti-MhPrx polyclonal antiserum. Probing of M. hyopneumoniae
      extracts with this antiserum demonstrated that MhPrx is expressed in all three
      tested strains (J, 7422 and 7448). Cross-linking assays and size-exclusion
      chromatography indicate that rMhPrx forms dimers, as has been established for
      atypical 2-Cys peroxiredoxins. Furthermore, a metal-catalysed oxidation system
      was used to assay the activity of rMhPrx, showing that it can protect DNA from
      ROS-mediated damage and may play an essential role during infection.

PMID- 19589830
TI  - Major impacts on the primary metabolism of the plant pathogen Cryphonectria
      parasitica by the virulence-attenuating virus CHV1-EP713.
AB  - Cryphonectria parasitica, the chestnut blight fungus, can be infected by
      virulence-attenuating mycoviruses of the family Hypoviridae. Previous studies
      have led to the hypothesis that the hypovirus-infected phenotype is partly due to
      metabolic changes induced by the viral infection. To investigate this, we
      measured the metabolic rate and respiration of C. parasitica colonies grown on
      solid medium. These experiments supported historical observations of other fungal
      species done in liquid cultures that the metabolic rate steadily declines with
      age and differentiation of the mycelium. Hypovirus infection increased metabolic
      rate in the youngest mycelium, but a subsequent decline was also observed as the
      mycelium aged. By measuring both CO(2) production and O(2) consumption, we also
      observed that changes occur in carbohydrate metabolism as a result of ageing in
      both infected and uninfected mycelium. Mycelium on the periphery of the colony
      exploited fermentation pathways extensively, before transitioning to aerobic
      carbohydrate metabolism and finally lipid metabolism in the interior regions,
      despite abundant remaining glucose. However, the hypovirus affected the extent of
      these changes, with infected mycelium apparently unable to utilize lipid-related
      metabolic pathways, leading to an increased depletion of glucose. Finally, we
      used metabolic profi fi ling to determine the changes in accumulation of primary
      metabolites in wild-type and hypovirus-infected mycelium and found that
      approximately one-third of the 164 detected metabolites were affected. These
      results are consistent with those expected from the physiological measurements,
      with significant alterations noted for compounds related to lipid and
      carbohydrate metabolism. Additionally, we observed an increase in the
      accumulation of the polyamine spermidine in the presence of hypovirus. Polyamines
      have been implicated in antiviral responses of mammalian systems; therefore this
      may suggest a novel antiviral response mechanism in fungi.

PMID- 19589832
TI  - Truncation in the core oligosaccharide of lipopolysaccharide affects flagella
      mediated motility in Pseudomonas aeruginosa PAO1 via modulation of cell surface
      attachment.
AB  - In many Gram-negative bacterial species, rough strains producing truncated
      lipopolysaccharide (LPS) generally exhibit defects in motility compared with
      smooth strains. However, the role that LPS plays in bacterial motility is not
      well understood. The goal of this study was to examine the relationship between
      LPS defects and motility of Pseudomonas aeruginosa. P. aeruginosa wild-type
      strain PAO1 and three isogenic mutants with defects in the rmlC, migA and wapR
      genes and producing truncated core oligosaccharide were investigated in terms of
      motility, attachment to glass and flagella expression. Compared with the wild
      type, the three mutants showed significant retardation in both swarming motility
      on 0.5 % soft-agar plates and swimming motility on 0.3 % soft-agar plates.
      Moreover, attachment to abiotic surfaces was observed to be stronger in these
      mutants. The assembly of flagella appeared to be intact in these strains and the
      ability of individual cells to swim was unaffected. Flagellin proteins prepared
      from mutants rmlC and rmd, defective in the production of TDP-l-rhamnose and GDP
      d-rhamnose, respectively, were compared and a change in molecular mass was
      observed only in the rmlC mutant. These data indicated that l-rhamnose, and not
      its enantiomer, d-rhamnose, is incorporated into the flagellin glycan of P.
      aeruginosa PAO1. The nucleotide-activated sugar precursor TDP-l-rhamnose is
      therefore shared between LPS biosynthesis and flagellin glycosylation in P.
      aeruginosa PAO1. Our results suggest that although biochemical precursors are
      shared by LPS and flagellin glycan biosynthesis, LPS truncations probably alter
      flagella-mediated motility in P. aeruginosa by modulating cell-surface attachment
      but not flagella synthesis.

PMID- 19589833
TI  - The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar
      Typhimurium for O-antigen production, resistance to antimicrobial peptides and in
      vivo fitness.
AB  - The enzyme phosphoglucomutase (Pgm) catalyses the interconversion of glucose 1
      phosphate and glucose 6-phosphate and contributes to glycolysis and the
      generation of sugar nucleotides for biosynthesis. To assess the role of this
      enzyme in the biology of the pathogen Salmonella enterica serovar Typhimurium we
      have characterized a pgm deletion mutant in strain SL1344. Compared to SL1344,
      SL1344 pgm had impaired growth in vitro, was deficient in the ability to utilize
      galactose as a carbon source and displayed reduced O-antigen polymer length. The
      mutant was also more susceptible to antimicrobial peptides and showed decreased
      fitness in the mouse typhoid model. The in vivo phenotype of SL1344 pgm indicated
      a role for pgm in the early stages of infection, most likely through deficient O
      antigen production. Although pgm mutants in other pathogens have potential as
      live attenuated vaccine strains, SL1344 pgm was not sufficiently attenuated for
      such use.

PMID- 19589834
TI  - Genetic and biochemical identification of the chorismate mutase from
      Corynebacterium glutamicum.
AB  - Chorismate mutase (CM) catalyses the rearrangement of chorismate to prephenate
      and is also the first and the key enzyme that diverges the shikimate pathway to
      either tryptophan (Trp) or phenylalanine (Phe) and tyrosine (Tyr).
      Corynebacterium glutamicum is one of the most important amino acid producers for
      the fermentation industry and has been widely investigated. However, the gene(s)
      encoding CM has not been experimentally identified in C. glutamicum. In this
      study, the ncgl0819 gene, which was annotated as 'conserved hypothetical protein'
      in the C. glutamicum genome, was genetically characterized to be essential for
      growth in minimal medium, and a mutant deleted of ncgl0819 was a Phe and Tyr
      auxotroph. Genetic cloning and expression of ncgl0819 in Escherichia coli
      resulted in the formation of a new protein (NCgl0819) having CM activity. It was
      concluded that ncgl0819 encoded the CM of C. glutamicum (CM0819). CM0819 was
      demonstrated to be a homodimer and is a new member of the monofunctional CMs of
      the AroQ structural class. The CM0819 activity was not affected by Phe, Tyr or
      Trp. Two 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthases (DS0950 and
      DS2098, formerly NCgl0950 and NCgl2098) had been previously identified from C.
      glutamicum. CM0819 significantly stimulated DAHP synthase (DS2098) activity.
      Physical interaction between CM0819 and DS2098 was observed. When CM0819 was
      present, DS2098 activity was subject to allosteric inhibition by chorismate and
      prephenate. Conserved hypothetical proteins homologous to CM0819 were identified
      in all known Corynebacterium genomes, suggesting a universal occurrence of CM0819
      like CMs in the genus Corynebacterium.

PMID- 19589835
TI  - Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically
      alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague.
AB  - Deletion of the murein (Braun) lipoprotein gene, lpp, attenuates the Yersinia
      pestis CO92 strain in mouse models of bubonic and pneumonic plague. In this
      report, we characterized the virulence of strains from which the plasminogen
      activating protease (pla)-encoding pPCP1 plasmid was cured from either the wild
      type (WT) or the Deltalpp mutant strain of Y. pestis CO92 in the mouse model of
      pneumonic infection. We noted a significantly increased survival rate in mice
      infected with the Y. pestis pPCP(-)/Deltalpp mutant strain up to a dose of 5000
      LD(50). Additionally, mice challenged with the pPCP(-)/Deltalpp strain had
      substantially less tissue injury and a strong decrease in the levels of most
      cytokines and chemokines in tissue homogenates and sera when compared with the WT
      infected group. Importantly, the Y. pestis pPCP(-)/Deltalpp mutant strain was
      detectable in high numbers in the livers and spleens of some of the infected
      mice. In the lungs of pPCP(-)/Deltalpp mutant-challenged animals, however,
      bacterial numbers dropped at 48 h after infection when compared with tissue
      homogenates from 1 h post-infection. Similarly, we noted that this mutant was
      unable to survive within murine macrophages in an in vitro assay, whereas
      survivability of the pPCP(-) mutant within the macrophage environment was similar
      to that of the WT. Taken together, our data indicated that a significant and
      possibly synergistic attenuation in bacterial virulence occurred in a mouse model
      of pneumonic plague when both the lpp gene and the virulence plasmid pPCP1
      encoding the pla gene were deleted from Y. pestis.

PMID- 19589836
TI  - Survival of Salmonella inside activated macrophages - why bacteria will not
      understand the word NO?

PMID- 19589837
TI  - Role of MexZ and PA5471 in transcriptional regulation of mexXY in Pseudomonas
      aeruginosa.
AB  - MexXY, a drug efflux pump in Pseudomonas aeruginosa, confers resistance to
      aminoglycoside antibiotics. We recently reported that MexZ binds to the promoter
      region of the mexXY operon. Electrophoretic mobility shift assay (EMSA) using
      recombinant MexZ and oligonucleotide probes prepared from the intergenic region
      between mexZ and mexX revealed that MexZ binds to a 20 bp palindromic sequence.
      Culture of P. aeruginosa in the presence of tetracycline induced higher levels of
      MexX and MexZ, as measured by immunoblotting and EMSA, than in the absence of
      antibiotics. When MexZ was expressed by a mexZ expression plasmid, the plasmid
      borne MexZ repressed drug-induced MexX production, further confirming that MexZ
      acts as a repressor of the mexXY operon. PA5471 protein has been reported to be
      essential for drug-induced MexXY production. Similarly to that report, we
      observed that plasmid-borne PA5471 induced both MexX and MexZ production in PAO1
      cells. Interestingly, interaction between MexZ and PA5471 was observed in a yeast
      two-hybrid assay. Furthermore, EMSA and in vitro transcription assays revealed
      that interaction between PA5471 and MexZ reduced MexZ DNA-binding ability,
      leading to mexXY transcription. These findings contribute to the understanding of
      the molecular mechanisms underlying the transcriptional regulation of mexZ and
      mexXY by drug-induced PA5471 expression.

PMID- 19589839
TI  - Built environments and obesity in disadvantaged populations.
AB  - In the United States, health disparities in obesity and obesity-related illnesses
      have been the subject of growing concern. To better understand how obesity
      related health disparities might relate to obesogenic built environments, the
      authors conducted a systematic review of the published scientific literature,
      screening for studies with relevance to disadvantaged individuals or areas,
      identified by low socioeconomic status, black race, or Hispanic ethnicity. A
      search for related terms in publication databases and topically related resources
      yielded 45 studies published between January 1995 and January 2009 with at least
      100 participants or area residents that provided information on 1) the built
      environment correlates of obesity or related health behaviors within one or more
      disadvantaged groups or 2) the relative exposure these groups had to potentially
      obesogenic built environment characteristics. Upon consideration of the obesity
      and behavioral correlates of built environment characteristics, research provided
      the strongest support for food stores (supermarkets instead of smaller
      grocery/convenience stores), places to exercise, and safety as potentially
      influential for disadvantaged groups. There is also evidence that disadvantaged
      groups were living in worse environments with respect to food stores, places to
      exercise, aesthetic problems, and traffic or crime-related safety. One strategy
      to reduce obesity would involve changing the built environment to be more
      supportive of physical activity and a healthy diet. Based on the authors' review,
      increasing supermarket access, places to exercise, and neighborhood safety may
      also be promising strategies to reduce obesity-related health disparities.

PMID- 19589838
TI  - Anchoring and length regulation of Porphyromonas gingivalis Mfa1 fimbriae by the
      downstream gene product Mfa2.
AB  - Porphyromonas gingivalis, a causative agent of periodontitis, has at least two
      types of thin, single-stranded fimbriae, termed FimA and Mfa1 (according to the
      names of major subunits), which can be discriminated by filament length and by
      the size of their major fimbrilin subunits. FimA fimbriae are long filaments that
      are easily detached from cells, whereas Mfa1 fimbriae are short filaments that
      are tightly bound to cells. However, a P. gingivalis ATCC 33277-derived mutant
      deficient in mfa2, a gene downstream of mfa1, produced long filaments (10 times
      longer than those of the parent), easily detached from the cell surface, similar
      to FimA fimbriae. Longer Mfa1 fimbriae contributed to stronger autoaggregation of
      bacterial cells. Complementation of the mutant with the wild-type mfa2 allele in
      trans restored the parental phenotype. Mfa2 is present in the outer membrane of
      P. gingivalis, but does not co-purify with the Mfa1 fimbriae. However, co
      immunoprecipitation demonstrated that Mfa2 and Mfa1 are associated with each
      other in whole P. gingivalis cells. Furthermore, immunogold microscopy, including
      double labelling, confirmed that Mfa2 was located on the cell surface and likely
      associated with Mfa1 fimbriae. Mfa2 may therefore play a role as an anchor for
      the Mfa1 fimbriae and also as a regulator of Mfa1 filament length. Two additional
      downstream genes (pgn0289 and pgn0290) are co-transcribed with mfa1 (pgn0287) and
      mfa2 (pgn0288), and proteins derived from pgn0289, pgn0290 and pgn0291 appear to
      be accessory fimbrial components.

PMID- 19589840
TI  - Association of higher parental and grandparental education and higher school
      grades with risk of hospitalization for eating disorders in females: the Uppsala
      birth cohort multigenerational study.
AB  - Eating disorders are a leading cause of disease burden among young women. This
      study investigated associations of social characteristics of parents and
      grandparents, sibling position, and school performance with incidence of eating
      disorders. The authors studied Swedish females born in 1952-1989 (n = 13,376),
      third-generation descendants of a cohort born in Uppsala in 1915-1929. Data on
      grandparental and parental social characteristics, sibling position, school
      grades, hospitalizations, emigrations, and deaths were obtained by register
      linkages. Associations with incidence of hospitalization for eating disorders
      were studied with multivariable Cox regression, adjusted for age and study
      period. Overall incidence of hospitalization for eating disorders was
      32.0/100,000 person-years. Women with more highly educated parents and maternal
      grandparents were at higher risk (hazard ratio for maternal grandmother with
      higher education relative to elementary education = 6.5, 95% confidence interval:
      2.2, 19.3, adjusted for parental education). Independent of family social
      characteristics, women with the highest school grades had a higher risk of eating
      disorders (hazard ratio = 7.7, 95% confidence interval: 2.5, 24.1 for high
      compared with low grades in Swedish, adjusted for parental education). Thus,
      higher parental and grandparental education and higher school grades may increase
      risk of hospitalization for eating disorders in female offspring, possibly
      because of high internal and external demands.

PMID- 19589841
TI  - Heavy/Light-chain analysis of monoclonal gammopathies.

PMID- 19589842
TI  - The diagnosis of diabetes is changing: how implementation of hemoglobin A1c will
      impact clinical laboratories.

PMID- 19589843
TI  - Regarding REGARDS: Does inflammation explain racial and regional differences in
      cardiovascular disease risk?

PMID- 19589844
TI  - Assessment of kidney function for drug dosing.

PMID- 19589845
TI  - Catecholamine interference in enzymatic creatinine assays.
AB  - BACKGROUND: Enzymatic creatinine assays are routinely used in clinical
      laboratories to provide more accurate estimated glomerular filtration rates and
      to avoid a perceived lack of analytical specificity associated with picrate
      (Jaffe) methods. Negative interferences with the enzymatic creatinine assay,
      which we noted in several patients on dopamine or dobutamine, prompted our
      further investigation into interference of catecholamines with enzymatic methods.
      METHODS: Spiked solutions of dopamine, dobutamine, epinephrine, and
      norepinephrine were added to pooled sera at catecholamine concentrations
      consistent with clinically relevant dosing. Creatinine was measured enzymatically
      on the Roche P-Modular, Ortho Clinical Diagnostics Vitros 350, and Abbott i-STAT.
      Jaffe methods were performed on the Roche P-Modular and Siemens Dimension RxL. In
      10 patients receiving dopamine and/or dobutamine via a venous or arterial line we
      evaluated and compared the extent of in vivo creatinine interference in paired
      serum samples obtained by venipuncture and from indwelling catheters. RESULTS:
      All catecholamines caused significant negative interference with the Roche
      enzymatic creatinine assay, most pronounced for dopamine and dobutamine. The
      Vitros enzymatic assay demonstrated slight negative interferences, and i-STAT
      enzymatic and Jaffe methods were unaffected by the presence of catecholamines.
      Significant (P < 0.001) differences in creatinine concentrations by Roche
      enzymatic vs Jaffe methods were observed in venipuncture specimens compared with
      arterial or venous catheter specimens, suggesting dopamine and dobutamine
      reversibly adhere to the catheter lumen. CONCLUSIONS: Negative interferences were
      pronounced for Roche enzymatic results in blood samples obtained from indwelling
      catheters, a phenomenon not observed in peripheral draws. Physicians and
      laboratorians should be alert to the possibility of a falsely low creatinine
      result and reevaluate questionable samples using a method unaffected by
      catecholamines.

PMID- 19589846
TI  - Aptamer-based regionally protected PCR for protein detection.
AB  - BACKGROUND: DNA aptamers are single-stranded nucleotide sequences that bind
      specifically to target molecules. By combining the advantages of PCR for
      amplifying specific DNA sequences and aptamer technology, we have developed a new
      strategy to detect target molecules such as proteins. METHODS: Ovine follicle
      stimulating hormone alpha subunit (oFSHalpha) was used as the model protein to
      generate a specific DNA aptamer via an in vitro evolutionary process. A targeted
      regional-mapping approach and a target-capturing assay were used to identify the
      binding region on the aptamer molecule. In the detection assay, referred to as
      "aptamer-based regionally protected PCR" (ARP-PCR), the aptamer was allowed to
      bind to the target protein in solution before digestion with DNase I. The region
      of the aptamer bound to the target was protected from DNase I cleavage. The
      target-binding region of the aptamer protected from the enzymatic treatment was
      then amplified by the PCR. RESULTS: Aptamers against oFSHalpha were generated.
      Six sequences of 20 selected aptamer clones were identical. This aptamer sequence
      was divided into 4 regions according to the aptamer's secondary structure. From
      examination of the target-binding ability of each region, we determined the
      specific binding region, for which primers were designed. With the aptamer and
      primers to detect oFSHalpha by means of the ARP-PCR method, we were able to
      detect the target protein at concentrations as low as 10(-14) mol/L. CONCLUSIONS:
      Combining the use of a DNA aptamer with the PCR is a potentially useful analytic
      tool for detection of proteins at low concentrations. .

PMID- 19589847
TI  - Copy-number variation genotyping of GSTT1 and GSTM1 gene deletions by real-time
      PCR.
AB  - BACKGROUND: Structural variation in the human genome is increasingly recognized
      as being highly prevalent and having relevance to common human diseases. Array
      based comparative genome-hybridization technology can be used to determine copy
      number variation (CNV) across entire genomes, and quantitative PCR (qPCR) can be
      used to validate de novo variation or assays of common CNV in disease-association
      studies. Analysis of large qPCR data sets can be complicated and time-consuming,
      however. METHODS: We describe qPCR assays for GSTM1 (glutathione S-transferase mu
      1) and GSTT1 (glutathione S-transferase theta 1) gene deletions that can genotype
      up to 192 samples in duplicate 5-microL reaction volumes in <2 h on the ABI Prism
      7900HT Sequence Detection System. To streamline data handling and analysis of
      these CNVs by qPCR, we developed a novel interactive, macro-driven Microsoft
      Excel(R) spreadsheet. As proof of principle, we used our software to analyze CNV
      data for 1478 DNA samples from a family-based cohort. RESULTS: With only 8 ng of
      DNA template, we assigned CNV genotypes (i.e., 2, 1, or 0 copies) to either 96%
      (GSTM1) or 91% (GSTT1) of all DNA samples in a single round of PCR amplification.
      Genotyping accuracy, as ascertained by familial inheritance, was >99.5%, and
      independent genotype assignments with replicate real-time PCR runs were 100%
      concordant. CONCLUSIONS: The genotyping assay for GSTM1 and GSTT1 gene deletion
      is suitable for large genetic epidemiologic studies and is a highly effective
      analysis system that is readily adaptable to analysis of other CNVs. .

PMID- 19589848
TI  - Genetic diversification, vicariance, and selection in a polytypic frog.
AB  - Spatial patterns of heritable phenotypic diversity reflect the relative roles of
      gene flow and selection in determining geographic variation within a species. We
      quantified color differentiation and genetic divergence among 20 populations of
      the red-eyed tree frog (Agalychnis callidryas) in lower Central America.
      Phylogenetic analyses revealed 5 well-supported mitochondrial DNA clades, and we
      infer from our phylogeny that geographic barriers have played a large role in
      structuring populations. Two phenotypic characters varied independently among
      isolated population groups: Flank coloration distinguished Caribbean from Pacific
      individuals, whereas leg coloration exhibited a more complex geographic pattern.
      We detected 3 generalized spatial patterns of genetic and phenotypic diversity:
      1) phenotypic differentiation in the presence of historical connectivity, 2)
      phenotypic uniformity across genetically differentiated regions, and 3)
      codistribution of genetic and phenotypic characters. These patterns indicate that
      phenotypic diversification is highly regionalized and can result from spatial
      variation in localized adaptations, geographic isolation, genetic drift, and/or
      evolutionary stasis. Although the mode of selection underlying color variation
      was not the focal objective of this study, we discuss the possible roles of
      natural and sexual selection in mediating population differentiation. Our study
      underscores the fact that selection gradients vary across relatively small
      spatial scales, even in species that occupy relatively homogeneous environments.

PMID- 19589849
TI  - Genetic mapping of resistance to Phomopsis seed decay in the soybean breeding
      line MO/PSD-0259 (PI562694) and Plant Introduction 80837.
AB  - Resistance to Phomopsis seed decay (PSD) in soybean (Glycine max [L.] Merr.)
      could provide dependable control of this important disease that affects seed
      quality. Studies have shown that single dominant genes that are allelomorphically
      different confer low levels of PSD in MO/PSD-0259 and PI 80837. The objectives of
      this research were to identify simple sequence repeat (SSR) markers linked to
      genes for PSD resistance in PI 80837 and MO/PSD-0259 and to associate the
      resistance genes to known linkage groups. Crosses were made between the PSD
      susceptible cultivar Agripro 350 and each of the resistant lines MO/PSD-0259 and
      PI 80837. F(2) populations from each cross were grown and inoculated in the
      field. Individual plant reactions were characterized by determining the levels of
      seed infection, and DNA of F(2) plants was extracted for SSR analysis and
      mapping. F(2) segregation data showed that different single dominant genes
      condition PSD resistance in MO/PSD-0259 and PI 80837. Resistance in PI 80837 was
      linked to Sat_177 (4.3 cM) and Sat_342 (15.8 cM) on molecular linkage group (MLG)
      B2. In MO/PSD-0259, resistance was linked to Sat_317 (5.9 cM) and Sat_120 (12.7
      cM) on MLG F. These data support work by Berger and Minor (Berger RD, Minor HC.
      1999. An restriction fragment length polymorphism (RFLP) marker associated with
      resistance to Phomopsis seed decay in soybean PI 417479. Crop Sci 39:800-805.) in
      which PSD resistance in PI 417479, the resistant parent used to develop MO/PSD
      0259, was associated with RFLP marker A708 on MLG F. These SSR markers should be
      useful in selection for resistant genotypes in breeding programs.

PMID- 19589850
TI  - Response of mass media, tobacco industry and smokers to the introduction of
      graphic cigarette pack warnings in Australia.
AB  - BACKGROUND: In the year 2006, Australia introduced graphic cigarette packet
      warnings. Previous warnings were text only. New warnings include one of 14
      pictures, many depicting tobacco-related pathology. METHODS: This study monitored
      the roll-out of the health policy initiative using multiple methodologies. Print
      media coverage of new pack warnings was observed over 3 years. Story content was
      coded as positive (supportive of pack warnings), neutral or negative. An
      observational study of small random sample of metropolitan stores (n = 16) over 7
      months measured the pace of the roll-out in shops. Once new packs were readily
      available in stores, smokers (n = 152) were intercepted in city streets and asked
      about their reactions. RESULTS: Of the 67 media stories, 85% were positive or
      neutral about the new warnings and 15% were negative. Supportive content
      presented health benefits. Unsupportive content presented industry arguments.
      After the legislative change, it took 2 months before any new packs appeared in
      stores. After 6 months, the majority carried them. Newest images had highest
      recall among smokers. About 60% said new warnings detracted from the look of
      their brand. About 51% felt the increased risk of dying from smoking-related
      illness. About 38% felt motivated to quit. CONCLUSION: Plans by government to
      introduce graphic warnings were delayed up to 2 years, apparently by heavy
      industry lobbying. Actual widespread appearance in shops occurred several months
      after the implementation date. While media coverage of the new warnings reported
      the industry arguments against them, the balance of coverage was overwhelmingly
      positive. Smokers' initial reactions were in line with tobacco control
      objectives.

PMID- 19589851
TI  - Impact of physical therapist-directed exercise counseling combined with fitness
      center-based exercise training on muscular strength and exercise capacity in
      people with type 2 diabetes: a randomized clinical trial.
AB  - BACKGROUND: Assessing muscular strength (force-generating capacity) and exercise
      capacity in response to an intervention for people with type 2 diabetes is
      clinically important in the prevention of type 2 diabetes-related complications.
      OBJECTIVE: The purpose of this study was to investigate the impact of physical
      therapist-directed exercise counseling combined with fitness center-based
      exercise training on muscular strength and exercise capacity in people with type
      2 diabetes. DESIGN: This study was a randomized clinical trial. SETTING: The
      study was conducted on a university campus, with patient recruitment from the
      local community. PATIENTS: Twenty-four people with type 2 diabetes were randomly
      allocated to either a group that received physical therapist-directed exercise
      counseling plus fitness center-based exercise training (experimental group) or a
      group that received laboratory-based, supervised exercise (comparison group).
      INTERVENTION: The experimental group received physical therapist-directed
      exercise counseling on an exercise program and was provided access to a fitness
      center. The comparison group received the same exercise program as the
      experimental group while under supervision. MEASUREMENTS: For all participants,
      chest press, row, and leg press muscular strength (1-repetition maximum [in
      kilograms]) and exercise capacity (graded exercise test duration [in minutes])
      testing were conducted at baseline and 2 months later. RESULTS: No significant
      differences in improvements in muscular strength were found for the chest press
      (adjusted mean difference=1.2; 95% confidence interval [CI]=-5.5 to 7.8), row
      (adjusted mean difference=0.1; 95% CI=-9.0 to 9.1), or leg press (adjusted mean
      difference=2.7; 95% CI=-9.1 to 14.6) between the groups. No significant
      difference in improvement in exercise capacity (adjusted mean difference=0.2; 95%
      CI=-0.9 to 1.2) was found between the groups. LIMITATIONS: Lack of group
      allocation blinding and the small sample size were limitations of this study.
      CONCLUSIONS: The results suggest that physical therapist-directed exercise
      counseling combined with fitness center-based exercise training can improve
      muscular strength and exercise capacity in people with type 2 diabetes, with
      outcomes comparable to those of supervised exercise.

PMID- 19589852
TI  - Factors associated with surgeon referral for physical therapy in patients with
      traumatic lower-extremity injury: results of a national survey of orthopedic
      trauma surgeons.
AB  - BACKGROUND: Variation in referral rates for physical therapy exists at both the
      individual physician and practice levels. OBJECTIVE: The purpose of this study
      was to explore the influence of physician and practice characteristics on
      referral for physical therapy in patients with traumatic lower-extremity injury.
      DESIGN: A cross-sectional survey was conducted. METHODS: In 2007, a Web-based
      survey questionnaire was distributed to 474 surgeon members of the Orthopaedic
      Trauma Association. The questionnaire measured physician and practice
      characteristics, outcome expectations, and attitude toward physical therapy.
      Referral for physical therapy was based on case vignettes. RESULTS: The response
      rate was 58%. Surgeons reported that 57.6% of their patients would have a
      positive outcome from physical therapy and 24.2% would have a negative outcome.
      The highest physical therapy expectations were for the appropriate use of
      assistive devices (80.7%) and improved strength (force-generating capacity)
      (76.4%). The lowest outcome expectations were for improvements in pain (35.9%),
      coping with the emotional aspects of disability (44.1%), and improvements in
      workplace limitations (51.4%). Physicians reported that 32.6% of their patients
      referred for physical therapy would have no improvement beyond what would occur
      with a surgeon-directed home exercise program. Multivariate analyses showed
      positive physician outcome expectations to have the largest effect on referral
      for physical therapy (odds ratio=2.7, P<.001). CONCLUSIONS: The results suggest
      that orthopedic trauma surgeons refer patients for physical therapy based mostly
      on expectations for physical and motor outcomes, but may not be considering pain
      relief, return to work, and psychosocial aspects of recovery. Furthermore, low
      referral rates may be attributed to a preference for surgeon-directed home-based
      rehabilitation. Future research should consider the efficacy of physical therapy
      for pain, psychosocial and occupational outcomes, and exploring the differences
      between supervised physical therapy and physician-directed home exercise
      programs.

PMID- 19589853
TI  - Adhesive capsulitis: establishing consensus on clinical identifiers for stage 1
      using the DELPHI technique.
AB  - BACKGROUND: Adhesive capsulitis often is difficult to diagnose in its early stage
      and to differentiate from other commonly seen shoulder disorders with the
      potential to cause pain and limited range of movement. OBJECTIVES: The purpose of
      this study was to establish consensus among a group of experts regarding the
      clinical identifiers for the first or early stage of primary (idiopathic)
      adhesive capsulitis. DESIGN: A correspondence-based Delphi technique was used in
      this study. METHODS: Three sequential questionnaires, each building on the
      results of the previous round, were used to establish consensus. RESULTS: A total
      of 70 experts from Australia and New Zealand involved in the diagnosis and
      treatment of adhesive capsulitis completed the 3 rounds of questionnaires.
      Following round 3, descriptive statistics were used to screen the data into a
      meaningful subset. Cronbach alpha and factor analysis then were used to determine
      agreement among the experts. Consensus was achieved on 8 clinical identifiers.
      These identifiers clustered into 2 discrete domains of pain and movement. For
      pain, the clinical identifiers were a strong component of night pain, pain with
      rapid or unguarded movement, discomfort lying on the affected shoulder, and pain
      easily aggravated by movement. For movement, the clinical identifiers included a
      global loss of active and passive range of movement, with pain at the end-range
      in all directions. Onset of the disorder was at greater than 35 years of age.
      CONCLUSIONS: This is the first study to use the Delphi technique to establish
      clinical identifiers indicative of the early stage of primary (idiopathic)
      adhesive capsulitis. Although limited in differential diagnostic ability, these
      identifiers may assist the clinician in recognizing early-stage adhesive
      capsulitis and may inform management, as well as facilitate future research.

PMID- 19589854
TI  - Brief report: normative data on a structured interview for diabetes adherence in
      childhood.
AB  - OBJECTIVE: This study provides normative data, divided by age and gender, for the
      Diabetes Self-Management Profile (DSMP), an empirically supported structured
      interview that assesses adherence with the type 1 diabetes treatment regimen.
      Despite wide use, normative data on the DSMP have yet to be reported. METHODS:
      The sample included 444 parents and 275 youth with type 1 diabetes. The DSMP was
      administered by a trained clinician. RESULTS: For both child and parent ratings
      of adherence, means and standard deviations for the overall sample and
      subdivision by gender and three age groups are presented for normative
      comparisons. Subscale data (e.g., glucose monitoring, diet, exercise) are
      similarly presented. Lower adherence scores were reported among older adolescents
      relative to preadolescents. CONCLUSIONS: The literature has lacked normative data
      on pediatric diabetes adherence. These data present means and standard deviations
      for parent and child ratings of regimen adherence from a relatively large sample
      of youth with diabetes that can be utilized for normative comparisons for
      clinical and research purposes.

PMID- 19589855
TI  - RHO protein regulation of contraction in the human uterus.
AB  - The state of contraction in smooth muscle cells of the human uterus is dependent
      on the interaction of activated forms of actin and myosin. Ras homology (RHO)
      proteins are small monomeric GTP-binding proteins that regulate actin
      polymerisation and myosin phosphorylation in smooth muscle cells. Their action is
      determined by their level of expression, GTP-bound state, intracellular
      localisation and phosphorylated status. Agonist activated RHO proteins bind to
      effector kinases such as RHO kinase (ROCK) and diaphanous proteins (DIAPH) to
      regulate smooth muscle contraction by two mechanisms: ROCK activates smooth
      muscle myosin either by direct phosphorylation at Ser19/Thr18 or through
      inhibition of myosin phosphatase which is a trimeric protein regulated by ROCK
      and by other protein kinases. Actin-polymerising proteins such as DIAPH homolog 1
      increase filamentous actin assembly to enhance acto-myosin cross bridge formation
      and contraction. This review explores recent advances in RHO protein signalling
      in human myometrium and proposes areas of further research to investigate the
      involvement of these proteins in the regulation of uterine contractility in
      pregnancy and labour.

PMID- 19589856
TI  - Ovarian follicle development in Booroola sheep exhibiting impaired bone
      morphogenetic protein signalling pathway.
AB  - The role of bone morphogenetic proteins (BMPs) in the regulation of ovarian
      function has been extensively investigated but the mechanism of regulation is not
      well understood. The aim of this study was to investigate the effect of mutation
      in the BMP receptor in Booroola sheep on the number of primordial follicles and
      rate of follicle recruitment in comparison with that in normal merino sheep in
      vivo. Whole sheep ovaries at the time of birth, 1.5 and 5 years old were
      collected and processed for the follicle quantification, using computerised
      stereological methods and statistical analyses. At birth, the total number of
      primordial follicles in Booroola sheep was significantly lower than in merino
      sheep. At 1.5 and 5 years, a reversed pattern in favour of Booroola ewes was seen
      with significantly more primordial follicles than merino. In parallel, the rate
      of primordial follicle recruitment to developing cohort was substantially lower
      in Booroola ewes with only 51 and 66% of primordial follicle consumption at 1.5
      and 5 years respectively compared to 92 and 97% in merino ewes. On other hand,
      the mean numbers of developing primary follicles were smaller in Booroola sheep
      at the time of birth, yet, Booroola ewes possess more primary follicles than
      merino at 1.5 years. These findings suggest that attenuation of the intraovarian
      signalling pathway of BMPs may in fact be a successful means of rationalising
      follicle consumption, preventing unnecessary loss of follicles from the initial
      primordial follicle pool, hence increasing reproductive longevity and fertility.

PMID- 19589857
TI  - A bicontinental origin of polyploid Australian/New Zealand Lepidium species
      (Brassicaceae)? Evidence from genomic in situ hybridization.
AB  - BACKGROUND AND AIMS: Incongruence between chloroplast and nuclear DNA
      phylogenies, and single additive nucleotide positions in internal transcribed
      spacer (ITS) sequences of polyploid Australian/New Zealand (NZ) Lepidium species
      have been used to suggest a bicontinental hybrid origin. This pattern was
      explained by two trans-oceanic dispersals of Lepidium species from California and
      Africa and subsequent hybridization followed by homogenization of the ribosomal
      DNA sequence either to the Californian (C-clade) or to the African ITS-type (A
      clade) in two different ITS-lineages of Australian/NZ Lepidium polyploids.
      METHODS: Genomic in situ hybridization (GISH) was used to unravel the genomic
      origin of polyploid Australian/NZ Lepidium species. Fluorescence in situ
      hybridization (FISH) with ribosomal DNA (rDNA) probes was applied to test the
      purported ITS evolution, and to facilitate chromosome counting in high-numbered
      polyploids. KEY RESULTS: In Australian/NZ A-clade Lepidium polyploids, GISH
      identified African and Australian/NZ C-clade species as putative ancestral
      genomes. Neither the African nor the Californian genome were detected in
      Australian/NZ C-clade species and the Californian genome was not detected in
      Australian/NZ A-clade species. Five of the eight polyploid species (from 7x to
      11x) displayed a diploid-like set of rDNA loci. Even the undecaploid species
      Lepidium muelleriferdinandi (2n = 11x = 88) showed only one pair of each rDNA
      repeat. In A-clade allopolyploids, in situ rDNA localization combined with GISH
      corroborated the presence of the African ITS-type. CONCLUSIONS: The nuclear
      genomes of African and Australian/NZ C-clade species were detected by GISH in
      allopolyploid Australian/NZ Lepidium species of the A-clade, supporting their
      hybrid origin. The presumed hybrid origin of Australian/NZ C-clade taxa could not
      be confirmed. Hence, it is assumed that Californian ancestral taxa experienced
      rapid radiation in Australia/NZ into extant C-clade polyploid taxa followed by
      hybridization with African species. As a result, A-clade allopolyploid Lepidium
      species share the Californian chloroplast type and the African ITS-type with the
      C-clade Australian/NZ polyploid and African diploid species, respectively.

PMID- 19589858
TI  - Impact of melatonin and molecular clockwork components on the expression of
      thyrotropin beta-chain (Tshb) and the Tsh receptor in the mouse pars tuberalis.
AB  - Photoperiodic regulation of reproduction in birds and mammals involves
      thyrotropin beta-chain (TSHb), which is secreted from the pars tuberalis (PT) and
      controls the expression of deiodinase type 2 and 3 in the ependymal cell layer of
      the infundibular recess (EC) via TSH receptors (TSHRs). To analyze the impact of
      melatonin and the molecular clockwork on the expression of Tshb and Tshr, we
      investigated melatonin-proficient C3H wild-type (WT), melatonin receptor 1
      deficient (MT1-/-) or clockprotein PERIOD1-deficient (mPER1-/-) mice. Expression
      of Tshb and TSHb immunoreactivity in PT were low during day and high during the
      night in WT, high during the day and low during the night in mPER1-deficient, and
      equally high during the day and night in MT1-deficient mice. Melatonin injections
      into WT acutely suppressed Tshb expression. Transcription assays showed that the
      5' upstream region of the Tshb gene could be controlled by clockproteins. Tshr
      levels in PT were low during the day and high during the night in WT and mPER1
      deficient mice and equally low in MT1-deficient mice. Tshr expression in the EC
      did not show a day/night variation. Melatonin injections into WT acutely induced
      Tshr expression in PT but not in EC. TSH stimulation of hypothalamic slice
      cultures of WT induced phosphorylated cAMP response element-binding protein in PT
      and EC and deiodinase type 2 in the EC. Our data suggest that Tshb expression in
      PT is controlled by melatonin and the molecular clockwork and that melatonin
      activates Tshr expression in PT but not in EC. They also confirm the functional
      importance of TSHR in the PT and EC.

PMID- 19589860
TI  - Inhibin B is a more potent suppressor of rat follicle-stimulating hormone release
      than inhibin a in vitro and in vivo.
AB  - Mature 31- and 34-kDa inhibin A and B negatively regulate the release of FSH from
      the anterior pituitary; however, a direct comparison of these hormones in vivo
      has not been undertaken. The bioactivities of highly purified preparations of
      recombinant human 31-kDa inhibin A and B were determined in rat pituitary cells
      in vitro, and in ovariectomized adult rats in vivo based on suppression of plasma
      FSH. The 31-kDa inhibin B was 4.2-fold more bioactive than inhibin A in vitro and
      1.45 (1.01-2.79)-fold more bioactive in vivo than 31-kDa inhibin A. However, the
      corresponding relative binding affinities of 31-kDa inhibin B for betaglycan,
      betaglycan+activin type II receptor (ActRII)-A, and betaglycan+ActRIIB were lower
      (IC(50) 2200, 400, and 750 pm, respectively) compared with 31-kDa inhibin A
      (IC(50) 190, 80, and 290 pm, respectively). A 2.7- and 2.5-fold reduction in in
      vitro bioactivity was observed between the 31- and 34-kDa inhibin A and 31- and
      34-kDa inhibin B, respectively, and these decreases in bioactivities were matched
      by a parallel reduction in binding to betaglycan and betaglycan+ActRIIA/B. It is
      concluded that the increased in vitro and in vivo bioactivities of 31-kDa inhibin
      B cannot be explained by a higher affinity to betaglycan or activin type II
      receptors; thus, additional factors mediate inhibin B's action. In addition,
      similar reductions in in vitro bioactivity and betaglycan+ActRIIA/B binding
      between 31- and 34-kDa inhibins A and B are attributed to hindrance by the
      additional carbohydrate group at Asn(302) in the formation of a functional
      inhibin+betaglycan+ActRIIA/B complex.

PMID- 19589859
TI  - Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes
      epigenetic alterations in adult ovarian genes.
AB  - Exposure to endocrine-disrupting chemicals during development could alter the
      epigenetic programming of the genome and result in adult-onset disease.
      Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and
      antiandrogenic activities. Previous studies showed that fetal/neonatal exposure
      to MXC caused adult ovarian dysfunction due to altered expression of key ovarian
      genes including estrogen receptor (ER)-beta, which was down-regulated, whereas
      ERalpha was unaffected. The objective of the current study was to evaluate
      changes in global and gene-specific methylation patterns in adult ovaries
      associated with the observed defects. Rats were exposed to MXC (20 microg/kgxd or
      100 mg/kg.d) between embryonic d 19 and postnatal d 7. We performed DNA
      methylation analysis of the known promoters of ERalpha and ERbeta genes in
      postnatal d 50-60 ovaries using bisulfite sequencing and methylation-specific
      PCRs. Developmental exposure to MXC led to significant hypermethylation in the
      ERbeta promoter regions (P < 0.05), whereas the ERalpha promoter was unaffected.
      We assessed global DNA methylation changes using methylation-sensitive
      arbitrarily primed PCR and identified 10 genes that were hypermethylated in
      ovaries from exposed rats. To determine whether the MXC-induced methylation
      changes were associated with increased DNA methyltransferase (DNMT) levels, we
      measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using
      semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b
      expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05),
      suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary.
      Overall, these data suggest that transient exposure to MXC during fetal and
      neonatal development affects adult ovarian function via altered methylation
      patterns.

PMID- 19589861
TI  - Mammalian target of rapamycin is activated in association with myometrial
      proliferation during pregnancy.
AB  - The adaptive growth of the uterus during gestation involves gradual changes in
      cellular phenotypes from the early proliferative to the intermediate synthetic
      phase of cellular hypertrophy, ending in the final contractile/labour phenotype.
      The mammalian target of rapamycin (mTOR) signaling pathway regulates cell growth
      and proliferation in many tissues. We hypothesized that mTOR was a mediator of
      hormone-initiated myometrial hyperplasia during gestation. The protein expression
      and phosphorylation levels of mTOR, its upstream regulators [insulin receptor
      substrate-1, phosphoinositide-3-kinase (PI3K), Akt], and downstream effectors [S6
      kinase-1 (S6K1) and eI4FE-binding protein 1 (4EBP1)] were analyzed throughout
      normal pregnancy in rats. In addition, we used an ovariectomized (OVX) rat model
      to analyze the modulation of the mTOR pathway and proliferative activity of the
      uterine myocytes by estradiol alone and in combination with the mTOR-specific
      inhibitor rapamycin. Our results demonstrate that insulin receptor substrate-1
      protein levels and the phosphorylated (activated) forms of PI3K, mTOR, and S6K1
      were significantly up-regulated in the rat myometrium during the proliferative
      phase of pregnancy. Treatment of the OVX rats with estradiol caused a transient
      increase in IGF-I followed by an up-regulation of the PI3K/mTOR pathway, which
      became apparent by a cascade of phosphorylation reactions (P-P85, P-Akt, P-mTOR,
      P-S6K1, and P-4EBP1). Rapamycin blocked activation of P-mTOR, P-S6K1, and P-4EBP1
      proteins and significantly reduced the number of proliferating cells in the
      myometrium of OVX rats. Our in vivo data demonstrate that estradiol was able to
      activate the PI3K/mTOR signaling pathway in uterine myocytes and suggest that
      this activation is responsible for the induction of myometrial hyperplasia during
      early gestation.

PMID- 19589862
TI  - Estradiol negative feedback regulation by glutamatergic afferents to A15
      dopaminergic neurons: variation with season.
AB  - It is now clear that seasonal breeding in ewes is due to an increase in response
      to estradiol (E(2)) negative feedback in the nonbreeding season (anestrus) that
      is mediated by the A15 group of dopaminergic (DA) neurons. Because A15 cells do
      not contain estrogen receptors, we have postulated the presence of estrogen
      responsive afferents and recently reported evidence that input from neurons
      containing gamma-aminobutyric acid (GABA) contribute to the control of A15
      activity by E(2). However, GABAergic afferents account for only a fraction of A15
      synaptic input and do not appear to vary with season. We therefore investigated
      the possible role of stimulatory glutamatergic input to A15 neurons. In
      experiments 1 and 2, local administration into the A15 of either a N-methyl-D
      aspartate (NMDA) receptor or a kainate/alpha-amino-3-hydroxyl-5-methyl-4
      isoxazole-propionate (AMPA) receptor antagonist stimulated episodic LH secretion
      in a dose-dependent manner in ovary-intact anestrous ewes. In experiment 3, we
      examined the number of glutamatergic close contacts onto A15 neurons using dual
      immunocytochemistry in tissue from E(2)-treated ovariectomized anestrous and
      breeding season ewes. All A15 DA neurons were contacted by glutamatergic
      vesicles, and the number of close contacts was significantly higher in anestrus
      than the breeding season. Finally, using a triple-label immunocytochemistry
      procedure, we did not observe any colocalization of markers for GABA and
      glutamate in vesicles contacting A15 neurons. These results support the
      hypothesis that glutamatergic afferents actively stimulate A15 DA neurons in
      ovary-intact anestrous ewes and raise the possibility that alterations in this
      input may contribute to increased A15 neural activity during anestrus.

PMID- 19589863
TI  - Dissociation between rat hippocampal CA1 and dentate gyrus cells in their
      response to corticosterone: effects on calcium channel protein and current.
AB  - Stress and corticosterone affect, via glucocorticoid receptors, cellular
      physiology in the rodent brain. A well-documented example concerns corticosteroid
      effects on high-voltage activated (L type) calcium currents in the hippocampal
      CA1 area. We tested whether corticosterone also affects calcium currents in
      another hippocampal area that highly expresses glucocorticoid receptors, i.e. the
      dentate gyrus (DG). Remarkably, corticosterone (100 nm, given for 20 min, 1-4.5
      hr before recording) did not change high-voltage activated calcium currents in
      the DG, whereas currents in the CA1 area of the same rats were increased. Follow
      up studies revealed that no apparent dissociation between the two areas was
      observed with respect to transcriptional regulation of calcium channel subunits;
      thus, in both areas corticosterone increased mRNA levels of the calcium channel
      beta4 but not the (alpha) Ca(v)1.2 subunit. At the protein level, however, beta4
      and Ca(v)1.2 levels were significantly up-regulated by corticosterone in the CA1
      but not the DG area. These data suggest that stress-induced elevations in the
      level of corticosterone result in a regionally differentiated physiological
      response that is not simply determined by the glucocorticoid receptor
      distribution and that the observed regional differentiation may be caused by a
      gene involved in the translational machinery or in mechanisms regulating mRNA or
      protein stability.

PMID- 19589864
TI  - Morphological ultrasound microimaging of thyroid in living mice.
AB  - The objective of the study was to explore high-frequency ultrasound (HFUS) for
      noninvasive microimaging of thyroid in living mice. Thyroid examination was
      performed by HFUS in 10 normal C57BL/6 mice, eight mice treated by
      propylthiouracil, and 22 Tg-TRK-T1 transgenic mice. The dimension of the gland
      and the presence of nodules were evaluated. Nodules were classified as malignant
      (hypoechogenicity, poorly defined margins, internal microcalcification, irregular
      shapes, and extra glandular extension) or not, and the findings were compared
      with histological data. Thyroid images were successfully obtained in all the
      animals analyzed. Normal thyroid reached a volume of 4.92 microl (range 2.11-4.92
      microl). Mice with propylthiouracil-induced goiter showed diffuse thyroid
      enlargement (median volume 6.67 microl, range 4.09-8.82 microl). In 19 of 22 Tg
      TRK-T1 mice (86%), HFUS identified a nodular process (the smallest detected
      nodule had a diameter of 0.46 mm). Eleven nodules were classified as malignant
      and eight as benign. Compared with histological analysis, HFUS showed a
      sensitivity of 100% in the detection of thyroid nodules and a specificity of 60%
      (two of the nodules identified by HFUS were not confirmed at the histology). The
      specificity and sensitivity of HFUS in predicting the malignancy of the thyroid
      nodules were 83 and 91%, respectively. Thus, HFUS is an accurate imaging modality
      that can potentially replace more invasive techniques, and, therefore, it
      represents a significant advancement in phenotypic assessment of mouse models of
      thyroid cancer.

PMID- 19589865
TI  - Increased mitogen-activated protein kinase kinase/extracellularly regulated
      kinase activity in human endometrial stromal fibroblasts of women with
      endometriosis reduces 3',5'-cyclic adenosine 5'-monophosphate inhibition of
      cyclin D1.
AB  - Endometriosis is characterized by endometrial tissue growth outside the uterus,
      due primarily to survival, proliferation, and neoangiogenesis of eutopic
      endometrial cells and fragments refluxed into the peritoneal cavity during
      menses. Although various signaling molecules, including cAMP, regulate
      endometrial proliferation, survival, and embryonic receptivity in endometrium of
      women without endometriosis, the exact molecular signaling pathways in
      endometrium of women with disease remain unclear. Given the persistence of a
      proliferative profile and differential expression of genes associated with the
      MAPK signaling cascade in early secretory endometrium of women with
      endometriosis, we hypothesized that ERK1/2 activity influences cAMP regulation of
      the cell cycle. Here, we demonstrate that 8-Br-cAMP inhibits bromodeoxyuridine
      incorporation and cyclin D1 (CCND1) expression in cultured human endometrial
      stromal fibroblasts (hESF) from women without but not with endometriosis.
      Incubation with serum-containing or serum-free medium resulted in higher phospho
      ERK1/2 levels in hESF of women with vs. without disease, independent of 8-Br-cAMP
      treatment. The MAPK kinase-1/2 inhibitor, U0126, fully restored cAMP down
      regulation of CCND1, but not cAMP up-regulation of IGFBP1, in hESF of women with
      vs. without endometriosis. Immunohistochemistry demonstrated the highest phospho
      ERK1/2 in the late-secretory epithelial and stromal cells in women without
      disease, in contrast to intense immunostaining in early-secretory epithelial and
      stromal cells in those with disease. These findings suggest that increased
      activation of ERK1/2 in endometrial cells from women with endometriosis may be
      responsible for persistent proliferative changes in secretory-phase endometrium.

PMID- 19589866
TI  - Comparison between hippocampus-synthesized and circulation-derived sex steroids
      in the hippocampus.
AB  - Estradiol (E2) and other sex steroids play essential roles in the modulation of
      synaptic plasticity and neuroprotection in the hippocampus. To clarify the
      mechanisms for these events, it is important to determine the respective role of
      circulating vs. locally produced sex steroids in the male hippocampus. Liquid
      chromatography-tandem mass spectrometry in combination with novel derivatization
      was employed to determine the concentration of sex steroids in adult male rat
      hippocampus. The hippocampal levels of 17beta-E2, testosterone (T), and
      dihydrotestosterone (DHT) were 8.4, 16.9, and 6.6 nm, respectively, and these
      levels were significantly higher than circulating levels. The hippocampal estrone
      (E1) level was, in contrast, very low around 0.015 nm. After castration to
      deplete circulating high level T, hippocampal levels of T and DHT decreased
      considerably to 18 and 3%, respectively, whereas E2 level only slightly decreased
      to 83%. The strong reduction in hippocampal DHT resulting from castration implies
      that circulating T may be a main origin of DHT. In combination with results
      obtained from metabolism analysis of [(3)H]steroids, we suggest that male
      hippocampal E2 synthesis pathway may be androstenedione --> T --> E2 or
      dehydroepiandrosterone --> androstenediol --> T --> E2 but not androstenedione -
      > E1 --> E2.

PMID- 19589867
TI  - Remission of type 1 diabetes after anti-CD3 antibody treatment and
      transplantation of embryonic pancreatic precursors.
AB  - Type 1 diabetes (T1D) mellitus is characterized by progressive autoimmune
      destruction of insulin producing beta-cells of the pancreatic islets of
      Langerhans. Cure of the disease will require control of autoimmunity to halt the
      destruction of beta-cells in the pancreas and restoration of beta-cell mass. We
      have built on the success of preclinical and clinical trials of anti-CD3 antibody
      treatment in modulating the immune response of T1D by the induction of tolerance
      and combined this treatment, using the nonobese diabetic mouse model, with a
      transplantation approach using fetal pancreatic anlagen as a source of beta-cell
      precursor or progenitor cells. Here we report that transplantation of pancreatic
      anlagen into diabetic nonobese diabetic mice rendered tolerant to the autoimmune
      process by treatment with anti-CD3 antibody resulted in long-term recovery from
      diabetes with restored metabolic control. Using a green fluorescent protein
      marker that made it possible to unequivocally identify the cells derived from the
      transplanted tissue, we show that the transplanted anlagen cells migrate to the
      host pancreas and provide a major source of insulin leading to restoration of
      normal glucose tolerance. Our results contrast with other studies that showed
      restoration of endogenous islets after infusion of spleen cells in mice treated
      with Freund's complete adjuvant and suggest that pancreatic fetal tissue has a
      tropism for the pancreatic site. This study suggests a novel mechanism of beta
      cell restoration by the migration of precursor cells or their progeny to the host
      pancreas and highlights the feasibility of using pancreatic precursors in
      combination with immune modulation as a treatment to effect long-term remission
      of T1D.

PMID- 19589868
TI  - The protein-tyrosine phosphatase, SRC homology-2 domain containing protein
      tyrosine phosphatase-2, is a crucial mediator of exogenous insulin-like growth
      factor signaling to human trophoblast.
AB  - Adequate fetal growth depends on placental transfer of nutrients and gases from
      the mother; thus, as pregnancy progresses, the placenta must grow to meet the
      increasing demands of the developing fetus. IGFs control proliferation,
      differentiation, and survival of trophoblast in first-trimester placenta via
      intracellular tyrosine kinase signaling cascades, the activation of which is also
      regulated by tyrosine phosphatases. The protein-tyrosine phosphatase, Src
      homology-2 domain containing protein tyrosine phosphatase (SHP)-2, is crucial for
      mouse placental development and is known to mediate IGF actions in other systems.
      In this study we examined the role of SHP-2 in regulating IGF-mediated
      proliferation in human trophoblast. Immunohistochemical analysis demonstrated
      that SHP-2 is expressed strongly in cytotrophoblast and only weakly in syncytium.
      After small interfering RNA-mediated knockdown of SHP-2 in BeWo choriocarcinoma
      cells and human first-trimester placental explants, IGF-induced trophoblast
      proliferation, examined using immunohistochemical analysis of Ki67 and 5-bromo-2'
      deoxyuridine incorporation, was significantly reduced (P < 0.05). Kinase
      activation assays suggested that SHP-2 interacts with the MAPK pathway to mediate
      these effects. Markers of trophoblast differentiation were elevated after SHP-2
      knockdown. This study demonstrates a role for tyrosine phosphatases in human
      trophoblast and establishes SHP-2 as a component of the IGF signaling pathway
      that is required for normal placental growth.

PMID- 19589869
TI  - Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is
      not required for ketogenesis and triglyceride clearance in liver.
AB  - Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse
      functions. Fgf21, a unique member of the Fgf family, is expected to function as a
      metabolic regulator in an endocrine manner. Hepatic Fgf21 expression was
      increased by fasting. The phenotypes of hepatic Fgf21 transgenic or knockdown
      mice and high-fat, low-carbohydrate ketogenic diet-fed mice suggests that Fgf21
      stimulates lipolysis in the white adipose tissue during normal feeding and is
      required for ketogenesis and triglyceride clearance in the liver during fasting.
      However, the physiological roles of Fgf21 remain unclear. To elucidate the
      physiological roles of Fgf21, we generated Fgf21 knockout (KO) mice by targeted
      disruption. Fgf21 KO mice were viable, fertile, and seemingly normal. Food
      intake, oxygen consumption, and energy expenditure were also essentially
      unchanged in Fgf21 KO mice. However, hypertrophy of adipocytes, decreased
      lipolysis in adipocytes, and decreased blood nonesterified fatty acid levels were
      observed when Fgf21 KO mice were fed normally. In contrast, increased lipolysis
      in adipocytes and increased blood nonesterified fatty acid levels were observed
      in Fgf21 KO mice by fasting for 24 h, indicating that Fgf21 stimulates lipolysis
      in the white adipose tissue during feeding but inhibits it during fasting. In
      contrast, unexpectedly, hepatic triglyceride levels were essentially unchanged in
      Fgf21 KO mice. In addition, ketogenesis in Fgf21 KO mice was not impaired by
      fasting for 24 h. The present results indicate that Fgf21 regulates lipolysis in
      adipocytes in response to the metabolic state but is not required for ketogenesis
      and triglyceride clearance in the liver.

PMID- 19589870
TI  - Resistin regulates pituitary somatotrope cell function through the activation of
      multiple signaling pathways.
AB  - The adipokine resistin is an insulin-antagonizing factor that also plays a
      regulatory role in inflammation, immunity, food intake, and gonadal function.
      Although adipose tissue is the primary source of resistin, it is also expressed
      in other tissues and organs, including the pituitary. However, there is no
      information on whether resistin, as described previously for other adipokines
      such as leptin and adiponectin, could regulate this gland. Likewise, the
      molecular basis of resistin actions remains largely unexplored. Here we show that
      administration of resistin to dispersed rat anterior pituitary cells increased GH
      release in both the short (4 h) and long (24 h) term, decreased mRNA levels of
      the receptor of the somatotrope regulator ghrelin, and increased free cytosolic
      Ca(2+) concentration in single somatotropes. By means of a pharmacological
      approach, we found that the stimulatory action of resistin occurs through a Gs
      protein-dependent mechanism and that the adenylate cyclase/cAMP/protein kinase A
      pathway, the phosphatidylinositol 3-kinase/Akt pathway, protein kinase C, and
      extracellular Ca(2+) entry through L-type voltage-sensitive Ca(2+) channels are
      essential players in mediating the effects of resistin on somatotropes. Taken
      together, our results demonstrate for the first time a regulatory role for
      resistin on somatotrope function and provide novel insights on the intracellular
      mechanisms activated by this protein.

PMID- 19589871
TI  - Trefoil factor-1 (TFF1) enhances oncogenicity of mammary carcinoma cells.
AB  - The functional role of autocrine trefoil factor-1 (TFF1) in mammary carcinoma has
      not been previously elucidated. Herein, we demonstrate that forced expression of
      TFF1 in mammary carcinoma cells resulted in increased total cell number as a
      consequence of increased cell proliferation and survival. Forced expression of
      TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology
      with increased cell migration and invasion. Moreover, forced expression of TFF1
      increased tumor size in xenograft models. Conversely, RNA interference-mediated
      depletion of TFF1 in mammary carcinoma cells significantly reduced anchorage
      independent growth and migration. Furthermore, neutralization of secreted TFF1
      protein by polyclonal antibody decreased mammary carcinoma cell viability in
      vitro and resulted in regression of mammary carcinoma xenografts. We have
      therefore demonstrated that TFF1 possesses oncogenic functions in mammary
      carcinoma cells. Functional antagonism of TFF1 can therefore be considered as a
      novel therapeutic strategy for mammary carcinoma.

PMID- 19589872
TI  - Hsa-miR-222 is involved in differentiation of endometrial stromal cells in vitro.
AB  - Decidualization is a critical step during embryo implantation and characterized
      by the differentiation of endometrial stromal cells (ESCs) into decidual cells.
      Because miRNAs are important determinants of cellular fate specification, in this
      study, the miRNA expression in ESCs during in vitro decidualization was profiled
      by using a microarray. Significance analysis of microarrays revealed that 49
      miRNA genes were differently (>2-fold) expressed between the noninduced ESCs and
      induced ESCs with a false discovery rate of 0. The expression variance of hsa-miR
      222, 221, 143, 101, 30d, 30c, 181b, 27b, 29b, 507, and 23a was validated by using
      quantitative PCR (P < 0.05). Based on microRNA (miRNA) and mRNA expression
      variance and predicted target genes of miRNAs, a bioinformatic model of miRNAs
      controlling ESCs differentiation was formulated. Finally, we proved that down
      regulation of has-miR-222 could decrease the number of cells in S phase during
      ESCs differentiation (P < 0.05). Antisense oligonucleotides of has-miR-222 could
      increase reporter gene expression by targeting the 3' untranslated regions of
      CDKN1C/p57kip2 mRNAs as well as increase CDKN1C/p57kip2 protein levels (P <
      0.05). In conclusion, our results suggest that a subset of miRNAs play a key role
      in gene reprogramming during ESCs decidualization and that hsa-miR-222
      participates in ESC differentiation by regulating ESCs terminally withdrawing
      from the cell cycle.

PMID- 19589873
TI  - 4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl-mediated decrease in serum
      thyroxine level in mice occurs through increase in accumulation of thyroxine in
      the liver.
AB  - 4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-CB187) was selected as a
      major hydroxylated polychlorinated biphenyl metabolite detected from serum of
      wildlife and humans and was examined for its effect on level of serum thyroid
      hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH
      CB187 (1.0 mg/kg), the serum total thyroxine (T(4)) and free T(4) levels were
      decreased in both strains of mice. On the other hand, no significant changes in
      the level and activity of the T(4)-UDP-glucuronosyltransferases, including UGT1a
      and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice.
      No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was
      observed in either strain of mice. Binding levels of [(125)I]T(4) to serum
      proteins after administration of [(125)I]T(4) were significantly changed in 4-OH
      CB187-pretreated mice: a decrease in the level of serum [(125)I]T(4)
      transthyretin (TTR) complex and an increase in the binding level of [(125)I]T(4)
      to serum albumin and thyroxine binding protein in both strains of mice. Clearance
      from serum of T(4) was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and
      DBA/2 mice, and the levels of T(4) in several tissues, especially the liver, were
      increased. In addition, 4-OH-CB187-mediated decreases in serum total T(4) and
      free T(4) levels were observed in wild-type and TTR-heterozygous mice but not in
      TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite
      ability to decrease serum T(4) level and further indicate that the 4-OH-CB187
      induced decrease would occur through increase in accumulation of T(4) in the
      liver.

PMID- 19589874
TI  - Multiple efflux pumps are involved in the transepithelial transport of
      colchicine: combined effect of p-glycoprotein and multidrug resistance-associated
      protein 2 leads to decreased intestinal absorption throughout the entire small
      intestine.
AB  - The purpose of this study was to thoroughly characterize the efflux transporters
      involved in the intestinal permeability of the oral microtubule polymerization
      inhibitor colchicine and to evaluate the role of these transporters in limiting
      its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance
      associated protein 2 (MRP2), and breast cancer resistance protein (BCRP)
      inhibitors on colchicine bidirectional permeability were studied across Caco-2
      cell monolayers, inhibiting one versus multiple transporters simultaneously.
      Colchicine permeability was then investigated in different regions of the rat
      small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2
      expression level throughout different intestinal segments was investigated by
      immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide
      (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7
      chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571),
      indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical
      (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration
      dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C
      (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced
      colchicine mucosal secretion, including complete abolishment of efflux
      (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant
      permeability along the rat small-intestine. GF120918 significantly increased
      colchicine permeability in the ileum with no effect in the jejunum, whereas MK571
      augmented jejunal permeability without changing the ileal transport. The
      GF120918/MK571 combination caused an effect similar to that of MK571 alone in the
      jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a
      gradient increasing from proximal to distal segments, whereas MRP2 decreased from
      proximal to distal small intestinal regions. Overall, it was revealed that the
      combined effect of P-gp and MRP2, but not BCRP, dominates colchicine
      transepithelial transport, leading to complete coverage of the entire small
      intestine, and makes the efflux transport dominate the intestinal permeability
      process.

PMID- 19589875
TI  - 24-hydroxycholesterol sulfation by human cytosolic sulfotransferases: formation
      of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and
      inhibition of liver x receptor activation.
AB  - 24-Hydroxycholesterol (24-OHChol) is a major cholesterol metabolite and the form
      in which cholesterol is secreted from the brain. 24-OHChol is transported by
      apolipoprotein E to the liver and converted into bile acids or excreted. In both
      brain and liver, 24-OHChol is a liver X receptor (LXR) agonist and has an
      important role in cholesterol homeostasis. 24-OHChol sulfation was examined to
      understand its role in 24-OHChol metabolism and its effect on LXR activation. 24
      OHChol was conjugated by three isoforms of human cytosolic sulfotransferase
      (SULT). SULT2A1 and SULT1E1 sulfated both the 3- and 24-hydroxyls to form the 24
      OHChol-3, 24-disulfate. SULT2B1b formed only 24-OHChol-3-sulfate. The 3-sulfate
      as a monosulfate or as the disulfate was hydrolyzed by human placental steroid
      sulfatase, whereas the 24-sulfate was resistant. At physiological 24-OHChol
      concentrations, SULT2A1 formed the 3-monosulfate and the 3, 24-disulfate as a
      result of a high affinity for sulfation of the 3-OH in 24-OHChol-24-sulfate.
      Molecular docking simulations indicate that 24-OHChol-24-sulfate binds in an
      active configuration in the SULT2A1 substrate binding site with high affinity
      only when the SULT2A1 homodimer structure was used. 24-OHChol is an LXR
      activator. In contrast, the 24-OHChol monosulfates were not LXR agonists in a
      fluorescence resonance energy transfer coactivator recruitment assay. However,
      both the 24-OHChol-3-sulfate and 24-sulfate were antagonists of LXR activation by
      N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trif-luoro-1-hydroxy-1
      (trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317) with an IC(50) of
      0.15 and 0.31 muM, respectively. Inhibition of LXR activation by the 24-OHChol
      monosulfates at low nanomolar concentrations indicates that sulfation has a role
      in LXR regulation by oxysterols.

PMID- 19589876
TI  - Functional characterization of low-prevalence missense polymorphisms in the UDP
      glucuronosyltransferase 1A9 gene.
AB  - The UDP-glucuronosyltransferase (UGT) 1A9 has been shown to play an important
      role in the detoxification of several carcinogens and clearance of anticancer and
      pain medications. The goal of the present study was to identify novel
      polymorphisms in UGT1A9 and characterize their effect on glucuronidation
      activity. The UGT1A9 gene was analyzed by direct sequencing of buccal cell
      genomic DNA from 90 healthy subjects. In addition to a previously identified
      single nucleotide polymorphism (SNP) at codon 33 resulting in an amino acid
      substitution (Met>Thr), two low-prevalence (<0.02) novel missense SNPs at codons
      167 (Val>Ala) and 183 (Cys>Gly) were identified and are present in both white and
      African-American subjects. Glucuronidation activity assays using HEK293 cell
      lines overexpressing wild-type or variant UGT1A9 demonstrated that the
      UGT1A9(33Thr) and UGT1A9(183Gly) variants exhibited differential glucuronidation
      activities compared with wild-type UGT1A9, but this was substrate-dependent. The
      UGT1A9(167Ala) variant exhibited levels of activity similar to those of wild-type
      UGT1A9 for all substrates tested. Whereas the wild-type and UGT1A9(33Thr) and
      UGT1A9(167Ala) variants formed homodimers as determined by Western blot analysis
      of native polyacrylamide gels, the UGT1A9(183Gly) variant was incapable of
      homodimerization. These results suggest that several low-prevalence missense
      polymorphisms exist for UGT1A9 and that two of these (M33T and C183G) are
      functional. These results also suggest that although Cys183 is necessary for
      UGT1A9 homodimerization, the lack of capacity for UGT1A9 homodimerization is not
      sufficient to eliminate UGT1A9 activity.

PMID- 19589877
TI  - Multi-domain misfolding: understanding the aggregation pathway of polyglutamine
      proteins.
AB  - The polyglutamine (polyQ) diseases consist of nine neurodegenerative diseases in
      which a polyQ tract expansion leads to protein misfolding and subsequent
      aggregation. Even when the causative proteins have the same length polyQ tract,
      there are differences in the severity and age of disease onset which implicate
      the polyQ flanking sequences as modulators of disease. Recent studies on the
      polyQ proteins ataxin-1, ataxin-3 and huntingtin exon-1 have shown that the
      flanking domains have an intrinsic ability to aggregate. This complex behavior
      leads to a multi-stage aggregation mechanism which we have termed multi-domain
      misfolding. In multi-domain misfolding, a flanking domain to the polyQ tract
      plays an early role in aggregation, before the contribution of the polyQ tract. A
      number of factors including the stability, dynamics and amyloidogenicity of the
      flanking domain modulate the impact on polyQ tract aggregation as well as any
      protein-protein interactions it undertakes. In this review, we examine the recent
      data in support of this novel mechanism of protein aggregation.

PMID- 19589878
TI  - FDTD calculations of SAR for child voxel models in different postures between 10
      MHz and 3 GHz.
AB  - Calculations of specific energy absorption rate (SAR) have been performed on the
      rescaled NORMAN 7-y-old voxel model and the Electronics and Telecommunications
      Research Institute (ETRI) child 7-y-old voxel model in the standing arms down,
      arms up and sitting postures. These calculations were for plane-wave exposure
      under isolated and grounded conditions between 10 MHz and 3 GHz. It was found
      that there was little difference at each resonant frequency between the whole
      body averaged SAR values calculated for the NORMAN and ETRI 7-y-old models for
      each of the postures studied. However, when compared with the arms down posture,
      raising the arms increased the SAR by up to 25%. Electric field values required
      to produce the International Commission on Non-Ionizing Radiation Protection and
      Institute of Electrical and Electronic Engineers public basic restriction were
      calculated, and compared with reference levels for the different child models and
      postures. These showed that, under certain worst-case exposure conditions, the
      reference levels may not be conservative.

PMID- 19589879
TI  - SENTINEL Project special initiative: ethical and justification issues in medical
      radiation protection.

PMID- 19589880
TI  - Ethical issues in radiology: perspectives from the Christian tradition.
AB  - The Christian ethical tradition introduces a number of key values into the
      clinical context. Moreover, although some denominational differences exist, these
      are essentially differences of emphasis rather than of substance. Among the
      central values which the Christian tradition promotes are: the dignity of the
      person, the individual as embodied spirit and the importance of the common good.
      Within the evolving discourse, social justice considerations have come to the
      fore as a critical concern within bioethics. In radiology, like most fields of
      clinical practice, practitioners frequently encounter conflicts and tensions of
      an ethical nature. Moreover, the manner in which these conflicts are articulated,
      conceptualised and ultimately resolved will depend, not only on how the
      scientific data are analysed and interpreted, but also on how different ethical
      frameworks are invoked in these disputes. The concern in this brief paper is to
      discuss the Christian ethical tradition as it is expressed in Roman Catholic and
      'Protestant' denominations in the western church, considering the values and
      norms that underlie Christian ethical engagements with applied questions.

PMID- 19589881
TI  - SENTINEL workshop on ethical issues in radiology: a perspective from the European
      Parliament.

PMID- 19589882
TI  - Report of a consultation on justification of patient exposures in medical
      imaging.
AB  - Radiation protection in medicine is underpinned by the concepts of justification
      and optimisation. Over the last 20 y much successful work has been devoted to
      developing and consolidating approaches to optimisation. A substantial knowledge
      base and a set of practical approaches have now been created to give effect to
      it. With respect to justification, less effort has been applied and the efforts
      applied have not yet been as successful. Authoritative sources suggest that a
      substantial fraction of radiological examinations may be unnecessary. In
      addition, a mainstream general medical journal has identified that few of those
      responsible for prescribing or performing examinations were familiar with the
      units used to specify the amount of radiation (and risk) received. This report
      sets out the conclusions of a consultation held in Vienna, by the International
      Atomic Energy Agency, dealing with the nature of justification and how to give
      effect to it in practice.

PMID- 19589883
TI  - Do family doctors have an obligation to facilitate research?
AB  - In the third of a series of articles examining ethical issues in primary care
      research, we argue that family doctors, when considering what they ought to do in
      relation to research, have a positive obligation to participate in research and
      that one means of discharging this obligation is to collaborate in research
      studies by aiding recruitment. We offer three arguments in support of this
      obligation-arguments from fairness, reason and utility. We then go on to specify
      a series of conditions on this obligation which take into account that doctors
      have many other obligations. These are the conditions of financial remuneration,
      reciprocity and ability.

PMID- 19589884
TI  - Waist circumference measurement: knowledge, attitudes and barriers in patients
      and practitioners in a multi-ethnic population.
AB  - BACKGROUND: Currently, body mass index (BMI) is widely used to identify health
      risk due to overweight or obesity. However, waist circumference is considered by
      many to be a better indicator of health risk than BMI. The primary health care
      team are ideally suited to screen for people at high risk of glucose intolerance
      and increased cardiovascular risk using waist circumference measurement (WCM).
      OBJECTIVES: To determine the knowledge and attitudes of patients and primary care
      practitioners concerning WCM, with particular reference to exploring barriers in
      a multi-ethnic setting. METHODS: A qualitative study using purposive sampling,
      semi-structured interviews and thematic analysis was conducted. Nine general
      practices were selected from Leicestershire, UK. The participants were 10
      practitioners (four practice nurses, six general practitioners) and 18 patients
      (six south Asians). RESULTS: Two overarching themes were identified from patient
      and practitioner interviews: understanding of waist size measurement to assess or
      monitor risk and attitudes related to perceived barriers and facilitators to
      waist measurement. A few practitioners felt uncomfortable about carrying out WCM
      and some perceived that patients might feel embarrassed. Practical barriers
      raised by professionals included lack of time, extra workload and financial
      implications. In contrast, patients generally raised few barriers to WCM. Being
      given an explanation appeared to be what was most important to them. No clear
      differences emerged when comparing views of patients from different ethnic groups
      or general practitioners and practice nurses. CONCLUSIONS: This study adds to our
      understanding of views on WCM in a multi-ethnic setting, highlighting factors for
      consideration if WCM is to be facilitated in routine practice.

PMID- 19589885
TI  - The effect of exercise on the cerebral vasculature of healthy aged subjects as
      visualized by MR angiography.
AB  - BACKGROUND AND PURPOSE: Prior studies suggest that aerobic exercise may reduce
      both the brain atrophy and the decline in fractional anisotropy observed with
      advancing age. It is reasonable to hypothesize that exercise-induced changes to
      the vasculature may underlie these anatomic differences. The purpose of this
      blinded study was to compare high-activity and low-activity healthy elderly
      volunteers for differences in the cerebrovasculature as calculated from vessels
      extracted from noninvasive MR angiograms (MRAs). MATERIALS AND METHODS: Fourteen
      healthy elderly subjects underwent MRA. Seven subjects reported a high level of
      aerobic activity (64 +/- 5 years of age; 5 men, 2 women) and 7, a low activity
      level (68 +/- 6 years of age; 5 women, 2 men). Following vessel segmentation from
      MRA by an individual blinded to subject activity level, quantitative measures of
      vessel number, radius, and tortuosity were calculated and histogram analysis of
      vessel number and radius was performed. RESULTS: Aerobically active subjects
      exhibited statistically significant reductions in vessel tortuosity and an
      increased number of small vessels compared with less active subjects.
      CONCLUSIONS: Aerobic activity in elderly subjects is associated with lower vessel
      tortuosity values and an increase in the number of small-caliber vessels. It is
      possible that an aerobic exercise program may contribute to healthy brain aging.
      MRA offers a noninvasive approach to visualizing the cerebral vasculature and may
      prove useful in future longitudinal investigations.

PMID- 19589886
TI  - Diffusion tensor imaging shows different topographic involvement of the thalamus
      in progressive supranuclear palsy and corticobasal degeneration.
AB  - BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal
      degeneration (CBD), postmortem studies show different topographic involvement of
      the thalamus, basal ganglia, and their cortical connections. Diffusion tensor
      imaging (DTI) is an MR imaging technique sensitive to gray and white matter
      microstructure integrity. This study was performed to determine whether DTI may
      demonstrate microstructural differences between PSP and CBD, particularly within
      the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients
      with probable PSP, 11 with probable CBD, and 7 controls formed the study group.
      Apparent diffusion coefficient average (ADC(ave)) and fractional anisotropy (FA)
      values were measured in regions of interest positioned in the ventrolateral
      (motor), medial, anterior, and posterior regions of the thalami, basal ganglia,
      fronto-orbital white matter, cingulum, supplementary motor area (SMA), and
      precentral and postcentral gyri in patients and controls. RESULTS: In PSP,
      ADC(ave) values were increased in several areas: the thalamus, particularly in
      its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were
      particularly decreased in the fronto-orbital white matter, anterior cingulum, and
      motor area. In CBD, ADC(ave) was increased in the motor thalamus, in the
      precentral and postcentral gyri, ipsilateral to the affected frontoparietal
      cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus
      and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients
      with PSP, thalamic involvement was diffuse and prevalent in its anterior part,
      whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI
      may be useful in the differential diagnosis of these 2 parkinsonian disorders.

PMID- 19589888
TI  - Soluble receptor for advanced glycation end products: a new biomarker in
      diagnosis and prognosis of chronic inflammatory diseases.
AB  - The formation of advanced glycation end products (AGEs) is a result of the non
      enzymatic reaction between sugars and free amino groups of proteins. AGEs,
      through interacting with their specific receptor for AGEs (RAGE), result in
      activation of pro-inflammatory states and are involved in numerous pathologic
      situations. The soluble form of RAGE (sRAGE) is able to act as a decoy to avoid
      interaction of RAGE with its pro-inflammatory ligands (AGEs, HMGB1, S100
      proteins). sRAGE levels have been found to be decreased in chronic inflammatory
      diseases including atherosclerosis, diabetes, renal failure and the aging
      process. The use of measuring circulating sRAGEs may prove to be a valuable
      vascular biomarker and in this review, we describe the implications of sRAGE in
      inflammation and propose that this molecule may represent a future therapeutic
      target in chronic inflammatory diseases.

PMID- 19589889
TI  - Comment on: Risk factors for severe cranial ischaemic events in an Italian
      population-based cohort of patients with giant cell arteritis.

PMID- 19589887
TI  - Rapid sequence evolution of transcription factors controlling neuron
      differentiation in Caenorhabditis.
AB  - Whether phenotypic evolution proceeds predominantly through changes in regulatory
      sequences is a controversial issue in evolutionary genetics. Ample evidence
      indicates that the evolution of gene regulatory networks via changes in cis
      regulatory sequences is an important determinant of phenotypic diversity.
      However, recent experimental work suggests that the role of transcription factor
      (TF) divergence in developmental evolution may be underestimated. In order to
      help understand what levels of constraints are acting on the coding sequence of
      developmental regulatory genes, evolutionary rates were investigated among 48 TFs
      required for neuronal development in Caenorhabditis elegans. Allelic variation
      was then sampled for 28 of these genes within a population of the related species
      Caenorhabditis remanei. Neuronal TFs are more divergent, both within and between
      species, than structural genes. TFs affecting different neuronal classes are
      under different levels of selective constraints. The regulatory genes controlling
      the differentiation of chemosensory neurons evolve particularly fast and exhibit
      higher levels of within- and between-species nucleotide variation than TFs
      required for the development of several neuronal classes and TFs required for
      motorneuron differentiation. The TFs affecting chemosensory neuron development
      are also more divergent than chemosensory genes expressed in the neurons they
      differentiate. These results illustrate that TFs are not as highly constrained as
      commonly thought and suggest that the role of divergence in developmental
      regulatory genes during the evolution of gene regulatory networks requires
      further attention.

PMID- 19589890
TI  - Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.
AB  - OBJECTIVE: It has been demonstrated that the endocannabinoid system is up
      regulated in pathologic fibrosis and that modulation of the cannabinoid receptors
      might limit the progression of uncontrolled fibrogenesis. The aim of this study
      was to investigate whether the synthetic cannabinoid receptor agonist WIN55,212-2
      could modulate fibrogenesis in an in vitro model of dcSSc. METHODS: The
      expression of cannabinoid receptors CB1 and CB2 was assessed in dcSSc fibroblasts
      and healthy control fibroblasts. To investigate the effect of WIN55,212-2 on
      dcSSc fibrogenesis, we studied type I collagen, profibrotic cytokines, fibroblast
      transdifferentiation into myofibroblasts, apoptotic processes and activation of
      the extracellular signal-related kinase 1/2 pathway prior to and after the
      treatment with the synthetic cannabinoid at increasing concentrations. RESULTS:
      Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with
      healthy controls. WIN55,212-2 caused a reduction in extracellular matrix
      deposition and counteracted several behavioural abnormalities of scleroderma
      fibroblasts including transdifferentiation into myofibroblasts and resistance to
      apoptosis. The anti-fibrogenic effect of WIN55,212-2 was not reverted by
      selective cannabinoid antagonists. CONCLUSIONS: Our preliminary findings suggest
      that cannabinoids are provided with an anti-fibrotic activity, thereby possibly
      representing a new class of agents targeting fibrosis diseases.

PMID- 19589891
TI  - A pilot risk model for the prediction of rapid radiographic progression in
      rheumatoid arthritis.
AB  - OBJECTIVES: Identifying patients with RA at high risk of rapid radiographic
      progression (RRP) is critical for making appropriate treatment decisions. We
      developed an exploratory prediction model for the risk of RRP using an RA study
      population undergoing either conservative or aggressive disease management.
      METHODS: Using data from the active-controlled study of patients receiving
      infliximab for the treatment of rheumatoid arthritis of early onset (ASPIRE)
      early RA study, RRP was defined as a threshold change in modified Sharp/van der
      Heijde score (SHS) of > or =5 U/year. Spearman's rank analysis was used to
      identify baseline risk factors for RRP. Logistic regression was used to calculate
      the probability of RRP in 1 year. The results were combined into a matrix model
      that consisted of risk factors and initiated treatment arranged in increasing
      risk of RRP. Data from the anti-TNF trial in rheumatoid arthritis with
      concomitant therapy (ATTRACT) established RA study were applied to the model to
      test its generalizability in another population. RESULTS: The 28 swollen joint
      count, RF, CRP and ESR are included as trichotomous variables and initiated
      treatment (monotherapy or combination therapy) as a dichotomous variable. Two
      models, one incorporating all risk factors except CRP and another incorporating
      all risk factors except ESR, were developed to adjust for collinearity. These
      models identify subpopulations of RA patients at higher predicted risk for RRP.
      CONCLUSIONS: These preliminary matrix models predict the risk of RRP using
      initiated treatment and easily accessible clinical and laboratory variables.
      Further testing in other populations and with other therapies is needed to obtain
      a definitive risk model that will guide rheumatologists in making treatment
      decisions for individual RA patients.

PMID- 19589893
TI  - Sudden visual loss in a patient with microscopic polyangiitis.

PMID- 19589894
TI  - Early response to COX-2 inhibitors as a predictor of overall response in
      osteoarthritis: pooled results from two identical trials comparing etoricoxib,
      celecoxib and placebo.
AB  - OBJECTIVE: We evaluated whether early response to NSAIDs predicted later
      response, and when this was established. METHODS: We evaluated pooled data from
      two identical 26-week, double-blind, randomized trials comparing once-daily
      etoricoxib 30 mg (n = 475), celecoxib 200 mg (n = 488) and placebo (n = 244) in
      patients with knee or hip OA. The present analysis was limited to the 12-week
      placebo-controlled period. Patient-level OMERACT-OARSI response was determined at
      2, 4, 8 and 12 weeks. The proportion of patients who maintained response status
      between these times was determined from binomial distribution using the exact
      method. RESULTS: After 12 weeks of treatment, there were significantly more
      responders in the etoricoxib (59.8%) and celecoxib (57%) groups compared with
      placebo (34%; P < 0.001 for etoricoxib or celecoxib vs placebo). About 77.2% of
      the patients receiving etoricoxib, 75.4% celecoxib and 58% placebo (P = 0.001 vs
      etoricoxib; P = 0.003 vs celecoxib) who were responders at 2 weeks were also
      responders at 12 weeks. When comparing response agreement (responder or non
      responder) at 2 weeks and 12 weeks, 74.3% of the patients receiving etoricoxib,
      73.2% celecoxib and 71.3% placebo had the same response status (kappa-coefficient
      0.459, 0.449 and 0.357, respectively). There were small incremental increases in
      agreement between Weeks 4 and 8 and 12 weeks. Logistic regression showed that
      agreement was not affected by index joint (P = 0.965). CONCLUSIONS: The
      overwhelming majority of the patients who responded to treatment by 2 weeks
      remained responders at 12 weeks, with response status largely established within
      2 weeks of treatment initiation. Early identification of NSAID response or non
      response may allow clinicians to better and more rapidly adjust symptomatic OA
      management.

PMID- 19589896
TI  - Injury and joint hypermobility syndrome in ballet dancers--a 5-year follow-up.

PMID- 19589898
TI  - Xylitol and capsular gene expression in Streptococcus pneumoniae.
AB  - Xylitol is a sugar alcohol that inhibits the growth and adherence of
      Streptococcus pneumoniae. In clinical trials, xylitol has been shown to decrease
      the occurrence of acute otitis media in day-care children but did not decrease
      nasopharyngeal carriage of the pneumococci. It has also been shown that xylitol
      affects the ultrastructure of the pneumococcal capsule. Here, it was hypothesized
      that xylitol might affect the expression of pneumococcal capsular genes. Capsule
      gene expression levels were studied in 24 clinical pneumococcal isolates and one
      ATCC strain (49619) by using a real-time RT-PCR method targeting the mRNA of the
      second gene of the pneumococcal capsular locus, the cpsB gene. The isolates were
      exposed to 5 % glucose, 5 % xylitol and control medium (brain heart infusion
      medium containing 10 % fetal bovine serum) for 2 h. cpsB gene expression levels
      were measured by using a relative quantification method with calibrator
      normalization where the 16S rRNA gene of pneumococcus was used as a reference.
      Exposure to xylitol lowered cpsB gene expression levels significantly compared
      with those in the control (P=0.035) and glucose (P=0.011) media. This finding
      supports previous results where exposure to xylitol changed the ultrastructure of
      the pneumococcal capsule and could explain further the high clinical efficacy of
      xylitol in preventing otitis media.

PMID- 19589899
TI  - Performance of an automated human immunodeficiency virus (HIV) antigen/antibody
      combined assay for prenatal screening for HIV infection in pregnant women.

PMID- 19589897
TI  - The p62 P392L mutation linked to Paget's disease induces activation of human
      osteoclasts.
AB  - Mutations of the gene encoding p62/SQSTM1 have been described in Paget's disease
      of bone (PDB), identifying p62 as an important player in osteoclast signaling. We
      investigated the phenotype of osteoclasts differentiated from peripheral blood
      monocytes obtained from healthy donors or PDB patients, all genotyped for the
      presence of a mutation in the p62 ubiquitin-associated domain. The cohort
      included PDB patients carrying or not the p62 P392L mutation and healthy donors
      carrying or not this mutation. Osteoclasts from PDB patients were more numerous,
      contained more nuclei, were more resistant to apoptosis, and had a greater
      ability to resorb bone than their normal counterparts, regardless of whether the
      p62 mutation was present or not. A strong increase in p62 expression was observed
      in PDB osteoclasts. The presence of the p62(P392L) gene in cells from healthy
      carriers conferred a unique, intermediate osteoclast phenotype. In addition, we
      report that two survival-promoting kinases, protein kinase Czeta and
      phosphoinositide-dependent protein kinase 1, were associated with p62 in response
      to receptor activator of NF-kappaB ligand (RANKL) stimulation in controls and
      before RANKL was added in PDB osteoclasts. In transfected osteoclasts derived
      from cord blood monocytes, the p62 P392L mutation contributed to increased
      activation of kinases protein kinase Czeta/lambda and phosphoinositide-dependent
      protein kinase 1, along with basal activation of NF-kappaB, independently of
      RANKL stimulation. These findings clearly indicate that the overexpression of p62
      in PDB patients induces important shifts in the pathways activated by RANKL and
      up-regulates osteoclast functions. Moreover, the most-commonly reported p62
      mutation, P392L, certainly contributes to the overactive state of osteoclasts in
      PDB.

PMID- 19589900
TI  - Characterization of Shigella sonnei isolates from travel-associated cases in
      Japan.
AB  - Shigella sonnei infection in industrialized countries is often associated with
      foreign travel. A total of 195 S. sonnei isolates in Japan, isolated from cases
      associated with foreign travel, were analysed by biotyping and molecular typing
      using PFGE and multilocus variable-number tandem-repeat analysis (MLVA); their
      antimicrobial susceptibilities were also evaluated. The isolates were from 26
      countries, most of which were Asian. Molecular typing revealed a correlation
      among the genotypes, biotypes and their geographical areas of origin. The
      isolates were classified into two biotypes, a and g. Biotype g isolates (n=178)
      were further divided into distinct clusters mainly on the basis of their
      geographical areas of origin by both PFGE and MLVA. Isolates from South Asian
      countries constituted one of the distinct clusters. Biotype g isolates from
      countries other than South Asia constituted other distinct clusters. Most of the
      isolates from other countries and continents, excluding the South Asian
      countries, were included in one major cluster by PFGE analysis. However, by MLVA,
      they were further divided into minor subclusters mainly on the basis of their
      countries of origin. MLVA was also demonstrated to be useful in molecular
      epidemiological analysis, even when only seven loci were applied, resulting in a
      high resolution with Simpson's index of diversity (D) of 0.993. A core drug
      resistance pattern of streptomycin, sulfisoxazole, tetracycline and trimethoprim
      sulfamethoxazole was observed in 108 isolates, irrespective of their geographical
      areas of origin, but the frequency of resistance to nalidixic acid was high among
      the South Asian and East Asian isolates. Two isolates from China and India were
      resistant to cefotaxime and harboured the bla(CTX-M-14) and bla(CTX-M-15) genes,
      respectively; these isolates were also resistant to nalidixic acid, which is a
      matter of concern in terms of shigellosis treatment. Use of a combination of
      methods was found to be effective for epidemiological investigation in the case
      of S. sonnei infection.

PMID- 19589902
TI  - Highly dynamic transient colonization by Staphylococcus aureus in healthy
      Malaysian students.

PMID- 19589901
TI  - A safety and feasibility study comparing an intermittent high dose with a daily
      standard dose of liposomal amphotericin B for persistent neutropenic fever.
AB  - A high intermittent dose regimen (group A: 10 mg kg(-1) on day 1, 5 mg kg(-1) on
      days 3 and 6) was compared with standard dosing (group B: 3 mg kg(-1) per day for
      14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent
      febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg
      (group B) was administered. Infusion-related adverse drug events, mainly
      rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than
      with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion
      time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the
      A : B ratio of the area under the curve for creatinine (AUC(CREATININE)) for days
      2-7 was 1.09 (P=0.27) and for days 2-14 was 1.05 (P=0.51). Rises in creatinine
      were mild (clinical toxicity criteria 1) in all patients with elevations.
      Hypokalaemia tended to be less severe in group A with a lower proportion of
      hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher
      AUC(POTASSIUM) (A : B ratio of 1.06, P=0.12), a lower proportion of patients with
      hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium
      supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly
      elevated median levels of serum bilirubin, alanine aminotransferase, aspartate
      aminotransferase and alkaline phosphatase, which were similar for the two
      regimens and were usually associated with other co-existing co-morbid conditions.
      The AUC for these enzymes was also similar in the two groups. No patient had
      discontinuation of the study drug due to toxicity. Composite success was
      identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients
      in group B and none in group A developed invasive fungal infections (IFIs). Beta
      D-Glucan levels were similar in both groups for patients without an IFI
      [AUC(GLUCAN) of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate
      of defervescence was similar for each regimen (P=0.75). This feasibility study
      suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg(-1) on
      days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg
      kg(-1) per day, with drug-acquisition cost savings and reduced drug exposure. A
      larger study is indicated for confirmation of this.

PMID- 19589903
TI  - Invasive meningococcal disease in Malta: an epidemiological overview, 1994-2007.
AB  - Since 1996, Malta has experienced an upsurge of invasive meningococcal disease
      (IMD) following an almost 30 year period with a negligible number of annually
      reported cases. We reviewed the 233 IMD cases notified during a 14 year period
      (1994-2007), and analysed epidemiological and laboratory surveillance data. The
      crude incidence per 100,000 inhabitants peaked in 2000 at 8.1 [95 % confidence
      interval (CI) 5.7-11.6] and again in 2006 at 8.9 (95 % CI 6.4-12.4), thereby
      placing Malta amongst the countries with the highest incidence of the disease in
      Europe. Of the total cases, 137 (59 %) were confirmed and 30 (13 %) were
      classified as probable. However, 66 cases (28 %) had no laboratory evidence of
      the disease and were classified as possible. Information on the serogroup was
      available for 114 cases. Serogroup B formed the largest proportion (76 %, n=87)
      followed by serogroup C (16 %, n=18). B : 4 : P1.19,15 strains (n=46)
      predominated throughout the study period since their first identification in
      1998. With 28 deaths attributed to IMD, the overall case fatality rate was 12 %.
      Apart from stressing the importance of maintaining high vigilance for IMD, our
      findings underscore the importance of enhancing laboratory surveillance of the
      disease, including characterization of the meningococci. Until vaccines against a
      broad range of serogroup B meningococci become available for universal use, the
      main methods of control remain the early treatment of cases and the prevention of
      secondary cases.

PMID- 19589904
TI  - Antifungal activity of the clove essential oil from Syzygium aromaticum on
      Candida, Aspergillus and dermatophyte species.
AB  - The composition and antifungal activity of clove essential oil (EO), obtained
      from Syzygium aromaticum, were studied. Clove oil was obtained commercially and
      analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3
      %). MICs, determined according to Clinical and Laboratory Standards Institute
      protocols, and minimum fungicidal concentration were used to evaluate the
      antifungal activity of the clove oil and its main component, eugenol, against
      Candida, Aspergillus and dermatophyte clinical and American Type Culture
      Collection strains. The EO and eugenol showed inhibitory activity against all the
      tested strains. To clarify its mechanism of action on yeasts and filamentous
      fungi, flow cytometric and inhibition of ergosterol synthesis studies were
      performed. Propidium iodide rapidly penetrated the majority of the yeast cells
      when the cells were treated with concentrations just over the MICs, meaning that
      the fungicidal effect resulted from an extensive lesion of the cell membrane.
      Clove oil and eugenol also caused a considerable reduction in the quantity of
      ergosterol, a specific fungal cell membrane component. Germ tube formation by
      Candida albicans was completely or almost completely inhibited by oil and eugenol
      concentrations below the MIC values. The present study indicates that clove oil
      and eugenol have considerable antifungal activity against clinically relevant
      fungi, including fluconazole-resistant strains, deserving further investigation
      for clinical application in the treatment of fungal infections.

PMID- 19589905
TI  - Outbreak of carbapenem-resistant Acinetobacter baumannii carrying the
      carbapenemase OXA-23 in a German university medical centre.
AB  - A prolonged outbreak of carbapenem-resistant Acinetobacter baumannii in a German
      university medical centre in 2006 was investigated; the investigation included a
      descriptive epidemiological analysis, a case-control study, environmental
      sampling, molecular typing of A. baumannii isolates using PFGE and repetitive
      sequence-based PCR (rep-PCR) typing, and detection of OXA-type carbapenemases by
      multiplex PCR. Thirty-two patients acquired the outbreak strain in five intensive
      care units (ICUs) and two regular wards at a tertiary care hospital within 10
      months. The outbreak strain was resistant to penicillins, cephalosporins,
      ciprofloxacin, gentamicin, tobramycin, imipenem and meropenem, and carried the
      bla(OXA-23)-like gene. Based on PFGE and rep-PCR typing, it was shown to be
      related to the pan-European A. baumannii clone II. The most likely mode of
      transmission was cross-transmission from colonized or infected patients via the
      hands of health-care workers, with the severity of disease and intensity of care
      (therapeutic intervention scoring system 28 score >median) being independently
      associated with acquisition of the outbreak strain (odds ratio 6.67, 95 %
      confidence interval 1.55-36.56). Control of the outbreak was achieved by
      enforcement of standard precautions, education of personnel, screening of ICU
      patients for carbapenem-resistant A. baumannii and cohorting of patients. This is
      believed to be the first report of an outbreak of A. baumannii carrying the
      carbapenemase OXA-23 in Germany.

PMID- 19589906
TI  - Frequency and molecular characteristics of ciprofloxacin- and rifampicin
      resistant Helicobacter pylori from gastric infections in the UK.
AB  - Treatment failure with standard Helicobacter pylori eradication regimes may
      require the use of 'rescue' therapies containing fluoroquinolones or rifamycins.
      The susceptibilities of H. pylori in the UK to such antimicrobials are unknown;
      therefore, this study aimed to determine the frequencies and molecular markers of
      resistance. Ciprofloxacin and rifampicin susceptibilities were determined by
      Etest and/or disc diffusion for 255 isolates of H. pylori, including 171 isolates
      from adult dyspeptic patients with refractive infections. Mutations in known
      resistance-determining regions of gyrA and rpoB were determined. The
      ciprofloxacin resistance rate was 7.5 %, and gyrA mutations, predominantly at
      codon position 91, were identified in most resistant isolates. One isolate (<1 %)
      had an unequivocal rifampicin-resistant phenotype by Etest yet had no associated
      mutations in the rpoB gene. As resistance rates were low in H. pylori isolates,
      including those from patients with refractive infections, it was concluded that
      fluoroquinolones or rifamycins might be considered in the UK for inclusion in
      'rescue' therapies.

PMID- 19589907
TI  - Shiga toxin-producing Escherichia coli infection in South India.

PMID- 19589908
TI  - Characterization of multidrug-resistant and extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae strains from Malaysian hospitals.
AB  - The emergence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase
      (ESBL)-producing Klebsiella pneumoniae poses a serious antibiotic management
      problem as resistance genes are easily transferred from one organism to another.
      Fifty-one strains of K. pneumoniae isolated from sporadic cases in various
      hospitals throughout Malaysia were analysed by antimicrobial susceptibility
      testing, PCR detection of ESBL-encoding genes and DNA fingerprinting. Although 27
      of the 51 K. pneumoniae strains were MDR (i.e. resistant to three or more classes
      of antibiotics), the majority of the strains (98 %) were sensitive to imipenem.
      PCR detection using ESBL gene-specific primers showed that 46 of the K.
      pneumoniae strains harboured bla(SHV), 19 harboured bla(CTX-M), 5 harboured
      bla(OXA-1) and 4 harboured bla(TEM-1). Class 1 integron-encoded intI1 integrase
      was detected in 21 of the 51 K. pneumoniae strains and amplification of the
      integron 5'CS region showed the presence of several known antibiotic resistance
      gene cassettes of various sizes. Results of conjugation and transformation
      experiments indicated that some of the ESBL-encoding genes (i.e. bla(SHV),
      bla(CTX-M) and bla(TEM-1)) were transmissible and were likely plasmid-encoded.
      DNA fingerprinting using PFGE and PCR-based methods indicated that the 51 K.
      pneumoniae strains were genetically diverse and heterogeneous.

PMID- 19589909
TI  - The beta104-109 sequence is essential for the secretion of correctly folded
      single-chain beta alpha horse LH/CG and for its FSH activity.
AB  - The dual LH and FSH activity of the equine LH (eLH)/equine chorionic gonadotropin
      (eCG) in heterologous species makes eLH/CG a good model to study
      structure/function relationships of gonadotropins. In order to bypass the problem
      of intracellular association of the heterodimer, a recombinant single-chain beta
      alpha eLH/CG was used to identify sequences in the beta-subunit involved in the
      secretion and activities of the hormone. The C-terminal region of the beta
      subunit was progressively truncated. All resulting truncated single-chains were
      secreted in the media as detected by an anti-beta peptide antibody in reducing
      conditions. However, using a conformation sensitive ELISA we show that the
      truncated single-chains were differently recognized: deletion of the last 40
      amino acids of the beta-subunit (beta109alpha eLH/CG) resulted in a 90% decrease
      in the recognized correctly folded hormone compared with the full-length beta
      alpha eLH/CG single-chain and no properly folded hormone was detected in the
      secretion medium when the last 46 amino acids of the beta-subunit were deleted
      (beta103alpha eLH/CG). We thus focused on the six amino acids sequence 104-109,
      which belongs to the seat-belt region. Mutation of the 104-109 sequence in
      alanines in the full-length beta alpha eLH/CG (beta104-109Ala alpha) led to a 50%
      decrease in the production of properly folded hormone in COS-7 as well as in
      alphaT3 pituitary cells. Moreover, the FSH activity of this mutant was decreased
      by 70% whereas its LH activity remained intact. These data lead us to conclude
      that the 104-109 region of the beta eLH/CG subunit is essential for the secretion
      of a fully folded beta alpha eLH/CG and for its FSH activity but not for its LH
      activity.

PMID- 19589910
TI  - Human aortic smooth muscle cells are insulin resistant at the receptor level but
      sensitive to IGF1 and IGF2.
AB  - Whether insulin, at physiological concentrations, has direct effects on vascular
      smooth muscle cells (VSMCs) remains controversial. Our aim was to characterize
      the mechanism for insulin resistance in VSMCs. For comparison, the effects of
      IGF1 and IGF2 were also studied. Cultured human aortic smooth muscle cells
      (HASMC) were used. Receptor mRNA was analyzed by quantitative reverse
      transcription PCR and receptor protein by ELISA and western blot. Biological
      effects were studied by thymidine incorporation and glucose accumulation. In
      HASMC, both mRNA and protein expression of IGF1 receptors (IGF1R) were fivefold
      higher compared to insulin receptor (IR). IR isoform A mRNA was 13-fold more
      expressed than IR isoform B. IR and IGF1R co-precipitated, indicating the
      presence of hybrid IR/IGF1R. Phosphorylation of the IGF1R beta-subunit was
      obtained by IGF1 10(-9)-10(-8) mol/l and IGF2 10(-8) mol/l. IR beta-subunit was
      phosphorylated by IGF1 10(-8) mol/l but not by insulin. IGF1 stimulated IR
      substrate-1 and AKT at 10(-8) mol/l and extracellular signal-regulated kinases 1
      and 2 at 10(-9)-10(-8) mol/l respectively. IGF1 and 2 at a concentration of 10(
      8)-10(-7) mol/l significantly stimulated (3)H-thymidine incorporation, whereas
      insulin did not. (14)C-Glucose accumulation was stimulated by IGF1 or IGF2 10(-8)
      10(-7) mol/l, and also by insulin 10(-7) mol/l. Our results suggest that IGF1R
      and hybrid IR/IGF1R are activated by physiological concentrations of IGF1 and 2
      in HASMC and this propagates downstream signaling and biological effects, while
      insulin has no effect on its receptor or downstream signaling probably due to a
      preponderance of IGF1R and incorporation of IR into hybrid IR/IGF1R.

PMID- 19589911
TI  - High incidence of low O(6)-methylguanine DNA methyltransferase expression in
      invasive macroadenomas of Cushing's disease.
AB  - CONTEXT: Crooke's cell adenoma (CCA), characterized by massive Crooke's hyaline
      change in corticotroph adenoma, causes a rare subtype of Cushing's disease. In
      contrast to ordinary corticotroph adenomas, CCAs are generally aggressive and
      present as invasive macroadenomas, which are refractory to both surgery and
      radiotherapy and have a high-recurrence rate. Moreover, some patients with CCA
      present with distant or craniospinal metastases. Currently, there are no
      effective standard therapies for CCA. OBJECTIVE: We report a patient with
      Crooke's cell carcinoma who presented with local invasion and liver metastases,
      which was refractory to conventional therapeutic modalities including
      transsphenoidal surgery, radiosurgery, medications, and hepatic transcatheter
      arterial embolization. After all these treatments failed, the patient had monthly
      temozolomide administrations, resulting in gradual clinical improvement and
      biochemical data that were consistent with tumor shrinkage. In glioblastoma, low
      O(6)-methylguanine DNA methyltransferase (MGMT) expression is associated with
      epigenetic gene silencing and predicts a better response to temozolomide.
      METHODS: We thus investigated MGMT expression, immunohistochemically, in seven
      CCAs (five invasive macroadenomas and two invasive microadenomas) and 17 ordinary
      type adenomas (OTAs; three noninvasive macroadenomas, 12 noninvasive
      microadenomas, and two invasive microadenomas) from patients with Cushing's
      disease. RESULTS: In seven CCAs, all five invasive macroadenomas exhibited low
      MGMT expression, defined as <5% nuclear MGMT staining. In 17 OTAs, only one
      adenoma showed low MGMT expression. CONCLUSION: In Cushing's disease, invasive
      macroadenomas including CCA usually have low-MGMT expression. Temozolomide thus
      may be a new therapeutic option for invasive macroadenomas such as CCA
      particularly when conventional treatments are ineffective.

PMID- 19589912
TI  - Isolation of stool-derived mucus provides a high yield of colonocytes suitable
      for early detection of colorectal carcinoma.
AB  - BACKGROUND: Promising stool-based screening tests for colorectal carcinoma (CRC)
      rely on detection of exfoliated colonocytes or their contents. However, methods
      of colonocyte retrieval have not been studied systematically and current
      approaches are restricted by low yields. We examined colonocyte numbers in stool
      wash fractions and assessed the suitability of retrieved cells for
      immunocytochemistry for minichromosome maintenance protein 2 (MCM2), a marker of
      the proliferative deregulation that characterizes malignancy. METHODS: Colonocyte
      numbers were accurately quantified in 129 wash fractions derived from 18 stools,
      comparing the mucus retained by a 125-microm filter (F fraction) with the fine
      and coarse content in the filtrate (S and P fractions, respectively). MCM2
      immunocytochemistry was done on sections of fibrin clot containing filter-derived
      mucus, obtained from stools of eight independent subjects. RESULTS: Total
      colonocyte yield in the F fraction (mean, 433.8 per 100 microL) was higher than
      in the S (140.3) and P (204.6) fractions (P = 0.004 and 0.03, respectively) due
      to increased numbers of morphologically abnormal cells, which predominantly
      represented malignant cells in samples from CRC patients. Several thousand
      abnormal cells could be obtained from stool-derived mucus in all CRC patients, an
      order of magnitude greater than numbers in subjects without CRC. Median MCM2
      labeling index in abnormal cells was 50% (range, 30-60%) in CRC patients and 0%
      in subjects without CRC. Cells in clot sections were well preserved and not
      obscured by fecal debris. CONCLUSIONS: Isolation of stool-derived mucus is
      technically straightforward and can improve the performance of protein-based
      and/or nucleic acid-based approaches to CRC screening.

PMID- 19589913
TI  - Relationship between migraine history and breast cancer risk among premenopausal
      and postmenopausal women.
AB  - Both migraine and breast cancer are hormonally mediated diseases, and it is
      biologically plausible that women with a history of migraine may have a reduced
      breast cancer risk. However, this relationship has only been assessed in a single
      relatively small study that was unable to assess the effect of migraine triggers,
      which are also well-established breast cancer risk factors (e.g., use of alcohol
      and exogenous hormones), on the inverse association observed. Utilizing data on
      4,568 breast cancer cases and 4,678 controls who participated in a multicenter
      population-based case-control study in the United States, we evaluated the
      association between migraine history and breast cancer risk using unconditional
      logistic regression. Migraine history data were obtained from structured in
      person interviews. Women with a history of migraine had a reduced risk of breast
      cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did
      not differ by menopausal status, age at migraine diagnosis, use of prescription
      migraine medications, or when analyses were restricted to women who avoided
      various migraine triggers (including alcohol, exogenous hormones, and smoking).
      These data support a previous finding that a history of migraine may be
      associated with a reduced risk of breast cancer. It extends the prior report in
      observing that this relationship holds for both premenopausal and postmenopausal
      women and is independent of exposure to common migraine triggers.

PMID- 19589914
TI  - Influence of reproductive factors on mortality after epithelial ovarian cancer
      diagnosis.
AB  - INTRODUCTION: Although many studies have examined the influence of reproductive
      factors on ovarian cancer risk, few have investigated their effect on ovarian
      cancer survival. We examined the prognostic influence of reproductive factors on
      survival after ovarian cancer diagnosis. METHODS: We conducted a longitudinal
      analysis of 410 women, ages 20 to 54 years, who participated in the 1980 to 1982
      Cancer and Steroid Hormone study as incident ovarian cancer cases. We obtained
      their vital status by linking Cancer and Steroid Hormone records with
      Surveillance, Epidemiology, and End Results data. We used the Kaplan-Meier
      approach to estimate survival probabilities and Cox proportional hazards models
      to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS:
      During a median follow-up of 9.2 years, 212 women died. Of the reproductive
      factors examined, only age at menarche and number of lifetime ovulatory cycles
      (LOC) relative to age significantly predicted ovarian cancer survival. Risk for
      death was higher among women with highest number of LOC compared with those
      having fewest LOC (HR, 1.67; 95% CI, 1.20-2.33). Women with fewest LOC had the
      highest 15-year survival (56.7%; 95% CI, 47.8-64.6%), and women with the highest
      LOC had the poorest (33.3%; 95% CI, 25.3-41.5%). Women whose age at menarche was
      <12 years had a higher risk of death compared with women whose menses began at >
      or =14 years (HR, 1.51; 95% CI, 1.02-2.24). CONCLUSIONS: We found that high LOC
      and early age at menarche were associated with decreased survival after ovarian
      cancer.

PMID- 19589916
TI  - Unbalanced cancer status may undermine results on insulin and insulin-like growth
      factor.

PMID- 19589917
TI  - Identifying key questions to advance research and practice in cancer survivorship
      follow-up care: a report from the ASPO Survivorship Interest Group.

PMID- 19589918
TI  - Practice concepts expansion to practice concepts and policy analysis.

PMID- 19589919
TI  - Office-based interventions for recognizing abnormal pediatric blood pressures.
AB  - Interventions to improve pediatric blood pressure (BP) screening have not been
      well studied. The authors measured staff acceptance of 2 simple in-office
      interventions and measured the effect on physician recognition of elevated BP
      measurements. Group 1 used simplified normative pediatric BP tables affixed to
      the growth chart, group 2 used a personal digital assistant program (PDA) to
      calculate BP percentiles as part of the vital signs, and group 3 served as the
      control. Group detection rates by compliant (C) and noncompliant (NC) with the
      intervention were: (1) (BP table) C = 18%, NC = 12%; (2) (PDA) C = 33%, NC = 26%;
      and (3) (control) 18%. There was no statistically significant intervention effect
      with documented compliance (P = .27) nor was there an effect in the noncompliant
      records (P = .12). Although the interventions were used inconsistently, their
      presence in the medical record did not improve performance. Future education and
      interventions are needed to reduce barriers to elevated pediatric BP recognition.

PMID- 19589920
TI  - Radiation therapy for HIV-associated diffuse large cell non-Hodgkin lymphoma.
AB  - PURPOSE: To report the clinical experience with external beam radiotherapy (RT)
      for AIDS-related lymphoma (ARL) with or without the involvement of the central
      nervous system (CNS) in HIV-infected patients. PATIENTS AND METHODS: Clinical
      outcome of 24 HIV-seropositive patients with ARL treated with RT from 1995 to
      2004 was reviewed, testing factors associated with outcome. RESULTS: After 1 and
      5 years, the overall survival was 65% and 35%, respectively. The mean RT dose was
      31 Gy after normalization to fractions of daily 2 Gy (range, 7.8-47.2 Gy).
      Radiotherapy dose was associated with survival in univariate (P = .04) and
      multivariate analysis (P = .01). Other factors in univariate analysis associated
      with outcome were viral load (VL), highly active antiretroviral therapy (HAART),
      ARL stage, and CNS involvement. Patients with CNS involvement achieved complete
      response in 46% and improved clinical performance was seen in 73%. CONCLUSIONS:
      After chemotherapy, RT in combination with HAART is highly active, and RT should
      be encouraged especially after suboptimal responses to induction treatment.

PMID- 19589921
TI  - How isometric are the medial patellofemoral, superficial medial collateral, and
      lateral collateral ligaments of the knee?
AB  - BACKGROUND: Ligament isometry is a cornerstone in the description of normal knee
      function and thorough knowledge is mandatory for successful repair of torn
      ligaments. PURPOSE: This study was undertaken to validate a novel experimental
      model for the study of ligament strains and to determine the length changes in
      the superficial medial collateral, lateral collateral, and medial patellofemoral
      ligaments. STUDY DESIGN: Descriptive laboratory study. METHODS: Passive motions
      and loaded squats of 12 cadaveric specimens were performed while controlling
      ankle load and optically tracking the motion of the bones. Preexperiment and
      postexperiment computed axial tomography scans allow the transformation of rigid
      body motion to relative motion of relevant anatomic landmarks on the femur,
      tibia, and patella. RESULTS: The superficial medial collateral ligament is a near
      isometric ligament with a strain of less than 2%. The ligament is a little more
      slack in midflexion (30 degrees to 50 degrees ) and in deep flexion, but length
      changes are not significant (P > .05). The lateral collateral ligament behaves
      near isometric (<2% strain) from 0 degrees to 70 degrees of knee flexion.
      Cartilage compression in a loaded environment relieves tension from the
      collateral ligaments (P < .05). The medial patellofemoral ligament is
      nonisometric. The cranial part of the medial patellofemoral ligament is most taut
      at full extension, while the caudal part is most taut at 30 degrees of knee
      flexion. CONCLUSION: Ligament insertion sites on the femur, patella, and fibula
      can be derived from computed axial tomography scans. The described model allows
      the study of dynamic ligament behavior. The superficial medial collateral
      ligament is a near-isometric ligament with no significant length changes. The
      medial patellofemoral ligament behaves differently in its cranial and caudal
      parts. CLINICAL RELEVANCE: In knees with chronic medial collateral ligament
      insufficiency, isometric repair of the superficial medial collateral ligament can
      be attempted. A medial patellofemoral ligament reconstruction with a double
      fixation on the medial patellar border is supported. The cranial bundle should be
      tightened at full extension and the caudal bundle at 30 degrees of knee flexion.

PMID- 19589922
TI  - Chelation of intracellular iron with the antifungal agent ciclopirox olamine
      induces cell death in leukemia and myeloma cells.
AB  - Off-patent drugs with previously unrecognized anticancer activity could be
      rapidly repurposed for this new indication. To identify such compounds, we
      conducted 2 independent cell-based chemical screens and identified the
      antimicrobial ciclopirox olamine (CPX) in both screens. CPX decreased cell growth
      and viability of malignant leukemia, myeloma, and solid tumor cell lines as well
      as primary AML patient samples at low-micromolar concentrations that appear
      pharmacologically achievable. Furthermore, oral CPX decreased tumor weight and
      volume in 3 mouse models of leukemia by up to 65% compared with control without
      evidence of weight loss or gross organ toxicity. In addition, oral CPX prevented
      the engraftment of primary AML cells in nonobese diabetic/severe combined
      immunodeficiency mouse models, thereby establishing its ability to target
      leukemia stem cells. Mechanistically, CPX bound intracellular iron, and this
      intracellular iron chelation was functionally important for its cytotoxicity. By
      electron paramagnetic resonance, CPX inhibited the iron-dependent enzyme
      ribonucleotide reductase at concentrations associated with cell death. Thus, in
      summary, CPX has previously unrecognized anticancer activity at concentrations
      that are pharmacologically achievable. Therefore, CPX could be rapidly repurposed
      for the treatment of malignancies, including leukemia and myeloma.

PMID- 19589923
TI  - Lack of specific gamma-retroviral vector long terminal repeat promoter silencing
      in patients receiving genetically engineered lymphocytes and activation upon
      lymphocyte restimulation.
AB  - Retroviral transduction of tumor antigen-specific T-cell receptor (TCR) genes
      into lymphocytes redirects T cells to lyse tumors. Furthermore, adoptive transfer
      of these lymphocytes has mediated objective responses in patients with metastatic
      cancer. From 2004 to 2006, more than 40 patients were treated with autologous
      gene-modified lymphocytes expressing a melanoma antigen-specific TCR at the
      National Cancer Institute. Eighteen such patients were analyzed for persistence
      and gene expression in vivo. In addition, the impact of epigenetic silencing and
      of lymphocyte restimulation was studied. Although gene-modified lymphocytes
      persisted in vivo, the shutdown of TCR transgene expression was observed.
      Bisulfite sequencing analysis and ex vivo DNA methyltransferase inhibition
      demonstrated that the decrease in gene expression did not result from DNA
      methylation. Surprisingly, down-regulation of vector-driven transgene
      transcriptional activity was not vector specific but mimicked that of endogenous
      genes. The decrease in TCR transgene expression, however, was reversed upon
      lymphocyte stimulation. These data demonstrate a lack of gamma-retroviral
      promoter-specific gene silencing in adoptively transferred human lymphocytes and
      support that transgene expression is largely affected by global cellular
      mechanisms. The use of immunomodulatory adjuvants, eg, vaccination or cytokine
      therapy, for in vivo T-cell activation may help overcome this metabolic
      quiescence and thus augment cellular immunotherapy-based cancer therapy.

PMID- 19589925
TI  - Selective reduction of JAK2V617F-dependent cell growth by siRNA/shRNA and its
      reversal by cytokines.
AB  - The JAK(V617F) mutation is responsible for the majority of breakpoint cluster
      region (BCR)/Abelson (ABL)-negative myeloproliferative disorders. Ongoing
      clinical trials of Janus kinase 2 (JAK2) inhibitors in myeloproliferative
      disorder patients use small molecules targeting both wild-type and mutated JAK2.
      To selectively target malignant cells, we developed JAK2(V617F)-specific small
      interfering RNAs or short hairpin RNAs. Expression of these RNAs in cell lines or
      CD34(+) cells from patients reduced JAK2(V617F)-driven autonomous cell
      proliferation. Mechanisms of inhibition involved selective JAK2(V617F) protein
      down-regulation, and consequently, decrease in signal transducer and activator of
      transcription 5 phosphorylation, cell-cycle progression, and cell survival.
      However, the addition of high concentrations of cytokines to cell lines or
      erythropoietin to patient cells greatly reduced growth inhibition. Similarly, the
      efficacy of a JAK2 small molecule inhibitor on cell line and patient cell
      proliferation dose dependently decreased with the addition of cytokines. Our
      results demonstrate that it is possible to specifically target JAK2(V617F) by RNA
      interference (RNAi) strategies. In addition, cytokines partially reverse the
      inhibition induced by both RNAi and small molecule approaches. This strongly
      suggests that patient cytokine levels in current JAK2 inhibitor clinical trials
      modulate the outcome of these therapies.

PMID- 19589924
TI  - Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl
      kinase domain mutations have a higher likelihood of developing additional
      mutations associated with resistance to second- or third-line tyrosine kinase
      inhibitors.
AB  - Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) developed to
      overcome imatinib resistance in Philadelphia-positive leukemias. To assess how
      Bcr-Abl kinase domain mutation status evolves during sequential therapy with
      these TKIs and which mutations may further develop and impair their efficacy, we
      monitored the mutation status of 95 imatinib-resistant patients before and during
      treatment with dasatinib and/or nilotinib as second or third TKI. We found that
      83% of cases of relapse after an initial response are associated with emergence
      of newly acquired mutations. However, the spectra of mutants conferring
      resistance to dasatinib or nilotinib are small and nonoverlapping, except for
      T315I. Patients already harboring mutations had higher likelihood of relapse
      associated with development of further mutations compared with patients who did
      not harbor mutations (23 of 51 vs 8 of 44, respectively, for patients who
      relapsed on second TKI; 13 of 20 vs 1 of 6, respectively, for patients who
      relapsed on third TKI).

PMID- 19589927
TI  - Opening act in a hematopoietic program.

PMID- 19589926
TI  - Identification and molecular characterization of recurrent genomic deletions on
      7p12 in the IKZF1 gene in a large cohort of BCR-ABL1-positive acute lymphoblastic
      leukemia patients: on behalf of Gruppo Italiano Malattie Ematologiche dell'Adulto
      Acute Leukemia Working Party (GIMEMA AL WP).
AB  - The BCR-ABL1 fusion gene defines the subgroup of acute lymphoblastic leukemia
      (ALL) with the worst clinical prognosis. To identify oncogenic lesions that
      combine with BCR-ABL1 to cause ALL, we used Affymetrix Genome-Wide Human SNP
      arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic
      polymerase chain reaction to study 106 cases of adult BCR-ABL1-positive ALL. The
      most frequent somatic copy number alteration was a focal deletion on 7p12 of
      IKZF1, which encodes the transcription factor Ikaros and was identified in 80
      (75%) of 106 patients. Different patterns of deletions occurred, but the most
      frequent were those characterized by a loss of exons 4 through 7 (Delta4-7) and
      by removal of exons 2 through 7 (Delta2-7). A variable number of nucleotides
      (patient specific) were inserted at the conjunction and maintained with fidelity
      at the time of relapse. The extent of the Delta4-7 deletion correlated with the
      expression of a dominant-negative isoform with cytoplasmic localization and
      oncogenic activity, whereas the Delta2-7 deletion resulted in a transcript
      lacking the translation start site. The IKZF1 deletion also was identified in the
      progression of chronic myeloid leukemia to lymphoid blast crisis (66%) but never
      in myeloid blast crisis or chronic-phase chronic myeloid leukemia or in patients
      with acute myeloid leukemia. Known DNA sequences and structural features were
      mapped along the breakpoint cluster regions, including heptamer recombination
      signal sequences recognized by RAG enzymes during V(D)J recombination, suggesting
      that IKZF1 deletions could arise from aberrant RAG-mediated recombination.

PMID- 19589928
TI  - Visualize eHPCs in different zones.

PMID- 19589929
TI  - Does IL-17 promote tumor growth?

PMID- 19589930
TI  - Suppressing the suppressor.

PMID- 19589931
TI  - Fibrinogen selects selectins.

PMID- 19589932
TI  - Feedback controversy stops here.

PMID- 19589933
TI  - Stage IV adult sporadic Burkitt lymphoma/leukemia with complex bone marrow
      cytogenetics is associated with a very poor outcome.

PMID- 19589935
TI  - Resistance of naturally occurring regulatory T cells toward oxidative stress:
      possible link with intracellular catecholamine content and implications for
      cancer therapy.

PMID- 19589937
TI  - PKCtheta in platelet activation.

PMID- 19589940
TI  - Beta1-tubulin gene mutation platelets are not macrothrombocytes.

PMID- 19589941
TI  - Hereditary hemochromatosis due to resistance to hepcidin: high hepcidin
      concentrations in a family with C326S ferroportin mutation.

PMID- 19589942
TI  - MRSA as a cause of postpartum breast abscess in infant and mother.
AB  - This report describes the unusual occurrence of mastitis and breast abscess in
      both mother and infant, both caused by methicillin-resistant Staphylococcus
      aureus (MRSA). Mother and child were both immunocompetent, and their only risk
      factor was routine confinement. The case highlights the importance of considering
      MRSA as a cause for mastitis in mothers and infants. MRSA is increasingly common,
      and failure to consider it as a cause for mastitis will lead to delays in
      treatment (as it did in this case). The case also demonstrates the role of
      Hospital in the Home in the treatment of postnatal infections, where
      hospitalization can be extremely disruptive.

PMID- 19589943
TI  - Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small
      intestinal injury: involvement of lactic acid.
AB  - Inflammatory responses triggered by activation of the lipopolysaccharide
      (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in
      nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study
      was to investigate the probiotic effect of Lactobacillus casei strain Shirota
      (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with
      viable LcS or heat-killed LcS once or once daily for a week were administered
      indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic
      acid (1-15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment
      with viable LcS prevented indomethacin-induced intestinal injury with increase in
      the concentration of lactic acid in small intestinal content and inhibited
      increases in myeloperoxidase activity and expression of mRNA for tumor necrosis
      factor-alpha (TNF-alpha) while affecting neither TLR4 expression nor the number
      of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS
      nor a single dose of viable LcS inhibited intestinal injury. Prevention of this
      injury was also observed in rats given l-lactic acid in drinking water. Both L
      lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF
      kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha
      protein secretion in THP-1 cells treated with LPS. Western blot analyses showed
      that both L-lactic acid and LcS culture supernatants suppressed phosphorylation
      and degradation of I-kappaB-alpha induced by LPS without affecting expression of
      TLR4. These findings suggest that LcS exhibits a prophylactic effect on
      indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway
      and that this probiotic effect of LcS may be mediated by L-lactic acid.

PMID- 19589944
TI  - Modulation of motor and sensory pathways of the peristaltic reflex by
      cannabinoids.
AB  - Cannabinoids have long been known to be potent inhibitors of intestinal and
      colonic propulsion. This effect has generally been attributed to their ability to
      prejunctionally inhibit release of acetylcholine from excitatory motor neurons
      that mediate, in part, the ascending contraction phase of the peristaltic reflex.
      In the present study we examined the effect of cannabinoids on the other
      transmitters known to participate in the peristaltic reflex using a three
      compartment preparation of rat colon that allows separation of ascending
      contraction, descending relaxation, and the sensory components of the reflex. On
      addition to the orad motor compartment, anandamide decreased and AM-251, a CB-1
      antagonist, increased ascending contraction and the concomitant substance P (SP)
      release. Similarly, on addition to the caudad motor compartment, anandamide
      decreased and AM-251 increased descending relaxation and the concomitant
      vasoactive intestinal peptide (VIP) release. On addition to the central sensory
      compartment, anandamide decreased and AM-251 increased both ascending contraction
      and SP release orad, and descending relaxation and VIP release caudad. This
      suggested a role for CB-1 receptors in modulation of sensory transmission that
      was confirmed by the demonstration that central addition of anandamide decreased
      and AM-251 increased release of the sensory transmitter, calcitonin gene-related
      peptide (CGRP). We conclude that the potent antipropulsive effect of cannabinoids
      is the result of inhibition of both excitatory cholinergic/tachykininergic and
      inhibitory VIPergic motor neurons that mediate ascending contraction and
      descending relaxation, respectively, as well as inhibition of the intrinsic
      sensory CGRP-containing neurons that initiate the peristaltic reflex underlying
      propulsive motility.

PMID- 19589945
TI  - Regeneration of intestinal stem/progenitor cells following doxorubicin treatment
      of mice.
AB  - The intestinal epithelium is in a constant state of renewal. The rapid turnover
      of cells is fed by a hierarchy of transit amplifying and stem/progenitor cells
      destined to give rise to the four differentiated epithelial lineages of the small
      intestine. Doxorubicin (Dox) is a commonly used chemotherapeutic agent that
      preferentially induces apoptosis in the intestinal stem cell zone (SCZ). We
      hypothesized that Dox treatment would initially decrease "+4" intestinal stem
      cell numbers with a subsequent expansion during mucosal repair. Temporal
      assessment following Dox treatment demonstrated rapid induction of apoptosis in
      the SCZ leading to a decrease in the number of intestinal stem/progenitor cells
      as determined by flow cytometry for CD45(-) SP cells, and immunohistochemistry of
      cells positive for putative +4 stem cell markers beta-cat(Ser552) and DCAMKL1.
      Between 96 and 168 h postinjection, overall proliferation in the crypts increased
      concomitant with increases in both absolute and relative numbers of goblet,
      Paneth, and enteroendocrine cells. This regeneration phase was also associated
      with increases of CD45(-) SP cells, beta-cat(Ser552)-positive cells, crypt
      fission, and crypt number. We used Lgr5-lacZ mice to assess behavior of Lgr5
      positive stem cells following Dox and found no change in this cell population.
      Lgr5 mRNA level was also measured and showed no change immediately after Dox but
      decreased during the regeneration phase. Together these data suggest that,
      following Dox-induced injury, expansion of intestinal stem cells occurs during
      mucosal repair. On the basis of available markers this expansion appears to be
      predominantly the +4 stem cell population rather than those of the crypt base.

PMID- 19589946
TI  - Hyperactivated B cells in human inflammatory bowel disease.
AB  - IBD is characterized by a chronic, dysregulated immune response to intestinal
      bacteria. Past work has focused on the role of T cells and myeloid cells in
      mediating chronic gastrointestinal and systemic inflammation. Here, we show that
      circulating and tissue B cells from CD patients demonstrate elevated basal levels
      of activation. CD patient B cells express surface TLR2, spontaneously secrete
      high levels of IL-8, and contain increased ex vivo levels of phosphorylated
      signaling proteins. CD clinical activity correlates directly with B cell
      expression of IL-8 and TLR2, suggesting a positive relationship between these B
      cell inflammatory mediators and disease pathogenesis. In contrast, B cells from
      UC patients express TLR2 but generally do not demonstrate spontaneous IL-8
      secretion; however, significant IL-8 production is inducible via TLR2
      stimulation. Furthermore, UC clinical activity correlates inversely with levels
      of circulating TLR2+ B cells, which is opposite to the association observed in
      CD. In conclusion, TLR2+ B cells are associated with clinical measures of disease
      activity and differentially associated with CD- and UC-specific patterns of
      inflammatory mediators, suggesting a formerly unappreciated role of B cells in
      the pathogenesis of IBD.

PMID- 19589949
TI  - Ovarian aging: mechanisms and clinical consequences.
AB  - Menopause is the final step in the process referred to as ovarian ageing. The age
      related decrease in follicle numbers dictates the onset of cycle irregularity and
      the final cessation of menses. The parallel decay in oocyte quality contributes
      to the gradual decline in fertility and the final occurrence of natural
      sterility. Endocrine changes mainly relate to the decline in the negative
      feedback from ovarian factors at the hypothalamo-pituitary unit. The declining
      cohort of antral follicles with age first results in gradually elevated FSH
      levels, followed by subsequent stages of overt cycle irregularity. The gradual
      decline in the size of the antral follicle cohort is best represented by
      decreasing levels of anti-Mullerian hormone. The variability of ovarian ageing
      among women is evident from the large variation in age at menopause. The
      identification of women who have severely decreased ovarian reserve for their age
      is clinically relevant. Ovarian reserve tests have appeared to be fairly accurate
      in predicting response to ovarian stimulation in the assisted reproductive
      technology (ART) setting. The capacity to predict the chances for spontaneous
      pregnancy or pregnancy after ART appears very limited. As menopause and the
      preceding decline in oocyte quality seem to have a fixed time interval, tests
      that predict the age at menopause may be useful to assess individual reproductive
      lifespan. Especially genetic studies, both addressing candidate gene and genome
      wide association, have identified several interesting loci of small genetic
      variation that may determine fetal follicle pool development and subsequent
      wastage of his pool over time. Improved knowledge of the ovarian ageing
      mechanisms may ultimately provide tools for prediction of menopause and
      manipulation of the early steps of folliculogenesis for the purpose of
      contraception and fertility lifespan extension.

PMID- 19589950
TI  - Molecular mechanisms underlying the activation of mammalian primordial follicles.
AB  - In humans and other mammalian species, the pool of resting primordial follicles
      serves as the source of developing follicles and fertilizable ova for the entire
      length of female reproductive life. One question that has intrigued biologists
      is: what are the mechanisms controlling the activation of dormant primordial
      follicles. Studies from previous decades have laid a solid, but yet incomplete,
      foundation. In recent years, molecular mechanisms underlying follicular
      activation have become more evident, mainly through the use of genetically
      modified mouse models. As hypothesized in the 1990s, the pool of primordial
      follicles is now known to be maintained in a dormant state by various forms of
      inhibitory machinery, which are provided by several inhibitory signals and
      molecules. Several recently reported mutant mouse models have shown that a
      synergistic and coordinated suppression of follicular activation provided by
      multiple inhibitory molecules is necessary to preserve the dormant follicular
      pool. Loss of function of any of the inhibitory molecules for follicular
      activation, including PTEN (phosphatase and tensin homolog deleted on chromosome
      10), Foxo3a, p27, and Foxl2, leads to premature and irreversible activation of
      the primordial follicle pool. Such global activation of the primordial follicle
      pool leads to the exhaustion of the resting follicle reserve, resulting in
      premature ovarian failure in mice. In this review, we summarize both historical
      and recent results on mammalian primordial follicular activation and focus on the
      up-to-date knowledge of molecular networks controlling this important
      physiological event. We believe that information obtained from mutant mouse
      models may also reflect the molecular machinery responsible for follicular
      activation in humans. These advances may provide a better understanding of human
      ovarian physiology and pathophysiology for future clinical applications.

PMID- 19589951
TI  - Modulation of alpha2-adrenoceptor functions by heterotrimeric Galphai protein
      isoforms.
AB  - Subtype diversity of heterotrimeric G proteins and G protein-coupled receptors
      enables a wide spectrum of signal transduction. However, the significance of
      isoforms within receptor or G protein subfamilies has not been fully elucidated.
      In the present study, we have tested whether alpha(2)-adrenoceptors require
      specific Galpha isoforms for their function in vivo. In particular, we analyzed
      the role of the highly homologous Galpha(i) isoforms, Galpha(i1), Galpha(i2), and
      Galpha(i3), in typical alpha(2)-adrenoceptor-controlled functions. Mice with
      targeted deletions in the genes encoding Galpha(i1), Galpha(i2), or Galpha(i3)
      were used to test the effects of alpha(2)-adrenoceptor stimulation by the agonist
      medetomidine. The alpha(2)-adrenoceptor agonist medetomidine inhibited
      [(3)H]norepinephrine release from isolated prefrontal brain cortex or cardiac
      atria tissue specimens with similar potency and efficacy in tissues from wild
      type or Galpha(i)-deficient mice. In vivo, bradycardia, hypotension, induction of
      sleep, antinociception, and hypothermia induced by alpha(2)-adrenoceptor
      activation did not differ between wild-type and Galpha(i)-knockout mice. However,
      the effects of the alpha(2)-agonists medetomidine or 5-bromo-6-(2-imidazolin-2
      ylamino)quin-oxaline tartrate (UK14,304) on spontaneous locomotor activity or
      anesthetic sparing were reduced or absent, respectively, in mice lacking
      Galpha(i2). In microdissected locus coeruleus neurons or postganglionic
      sympathetic neurons from stellate ganglia, all three Galpha(i) subunits were
      expressed as determined by quantitative reverse transcription-polymerase chain
      reaction, with Galpha(i1) and Galpha(i2) dominating over Galpha(i3). Functional
      redundancy of the highly homologous Galpha(i) isoforms may predominate over
      specificity to regulate distinct intracellular pathways downstream of alpha(2)
      adrenoceptors in vivo. In contrast, inhibition of locomotor activity and
      anesthetic sparing may be elicited by a specific coupling of alpha(2A)
      adrenoceptors via the Galpha(i2) isoform to intracellular pathways.

PMID- 19589952
TI  - Interaction between muscle temperature and contraction velocity affects
      mechanical efficiency during moderate-intensity cycling exercise in young and
      older women.
AB  - The effect of elevated muscle temperature on mechanical efficiency was
      investigated during exercise at different pedal frequencies in young and older
      women. Eight young (24 +/- 3 yr) and eight older (70 +/- 4 yr) women performed 6
      min periods of cycling at 75% ventilatory threshold at pedal frequencies of 45,
      60, 75, and 90 rpm under control and passively elevated local muscle temperature
      conditions. Mechanical efficiency was calculated from the ratio of energy
      turnover (pulmonary O(2) uptake) and mechanical power output. Overall, elevating
      muscle temperature increased (P < 0.05) mechanical efficiency in young (32.0 +/-
      3.1 to 34.0 +/- 5.5%) and decreased (P < 0.05) efficiency in older women (30.2 +/
      5.6 to 27.9 +/- 4.1%). The different effect of elevated muscle temperature in
      young and older women reflects a shift in the efficiency-velocity relationship of
      skeletal muscle. These effects may be due to differences in recruitment patterns,
      as well as sarcopenic and fiber-type changes with age.

PMID- 19589953
TI  - Protein and carbohydrate supplementation after exercise increases plasma volume
      and albumin content in older and young men.
AB  - This study examined whether increased plasma volume (PV) and albumin content
      (Alb(cont)) in plasma for 23 h after exercise were attenuated in older subjects
      compared with in young adult subjects, and if this attenuation abated by
      supplementation with protein and carbohydrate (CHO) immediately after exercise.
      Eight moderately active older (approximately 68 yr) and 8 young (approximately 21
      yr) men performed two trials: control (CNT) and Pro-CHO in which subjects
      consumed placebo (0.5 kcal, 0 g protein, 0.5 mg Na(+) in 3.2 ml total fluid
      volume/kg body wt) or protein and CHO mixture (3.2 kcal, 0.18 g protein, 0.5 mg
      Na(+) in 3.2 ml total fluid volume/kg body wt) supplementations, respectively,
      immediately after high-intensity interval exercise for 72 min [8 sets of 4 min at
      70-80% peak oxygen consumption rate (Vo(2peak)) intermitted by 5 min at 20%
      Vo(2peak)]. PV, Alb(cont), and plasma globulin content (Glb(cont)) were measured
      before exercise, at the end of exercise, every hour from the 1st to the 5th hour
      after exercise, and at the 23rd hour after exercise. From 12 h before the start
      to the end of experiment, food intake was controlled to the age-matched
      recommended dietary allowances. We found that during the first 4 h after exercise
      in CNT, Alb(cont) recovered less in the older than the young group by
      approximately 0.04 g/kg (P < 0.05), while it generally recovered more with Pro
      CHO than CNT by approximately 0.09 and approximately 0.04 g/kg in the young and
      older group, respectively, accompanied by a greater increase in PV by
      approximately 1 and approximately 2 ml/kg, respectively, during the 23 h after
      exercise (P < 0.05). Glb(cont) remained constant throughout the experiment in
      both trials for both age groups. Thus the attenuated responses of Alb(cont) and
      PV after exercise in older subjects were restored by protein and CHO
      supplementation immediately after exercise, similarly to young subjects.

PMID- 19589948
TI  - The role of liver-derived insulin-like growth factor-I.
AB  - IGF-I is expressed in virtually every tissue of the body, but with much higher
      expression in the liver than in any other tissue. Studies using mice with liver
      specific IGF-I knockout have demonstrated that liver-derived IGF-I, constituting
      a major part of circulating IGF-I, is an important endocrine factor involved in a
      variety of physiological and pathological processes. Detailed studies comparing
      the impact of liver-derived IGF-I and local bone-derived IGF-I demonstrate that
      both sources of IGF-I can stimulate longitudinal bone growth. We propose here
      that liver-derived circulating IGF-I and local bone-derived IGF-I to some extent
      have overlapping growth-promoting effects and might have the capacity to replace
      each other (= redundancy) in the maintenance of normal longitudinal bone growth.
      Importantly, and in contrast to the regulation of longitudinal bone growth,
      locally derived IGF-I cannot replace (= lack of redundancy) liver-derived IGF-I
      for the regulation of a large number of other parameters including GH secretion,
      cortical bone mass, kidney size, prostate size, peripheral vascular resistance,
      spatial memory, sodium retention, insulin sensitivity, liver size, sexually
      dimorphic liver functions, and progression of some tumors. It is clear that a
      major role of liver-derived IGF-I is to regulate GH secretion and that some, but
      not all, of the phenotypes in the liver-specific IGF-I knockout mice are
      indirect, mediated via the elevated GH levels. All of the described multiple
      endocrine effects of liver-derived IGF-I should be considered in the development
      of possible novel treatment strategies aimed at increasing or reducing endocrine
      IGF-I activity.

PMID- 19589954
TI  - Chronic intermittent hypoxia increases left ventricular contractility in C57BL/6J
      mice.
AB  - Intermittent hypoxia (IH) commonly occurs in patients with obstructive sleep
      apnea and can cause a wide range of pathology, including reduced left ventricular
      (LV) ejection fraction in rats as determined by echocardiography, in rodent
      models. We utilized echocardiography and pressure-volume (PV) loop analyses to
      determine whether LV contractility was decreased in inbred C57BL/6J mice exposed
      to IH and whether blockade of beta-adrenergic receptors modified the response to
      hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir
      inspired O(2) 5-6% at 60 cycles/h for 12 h during the light period) or
      intermittent air (IA) as control. A second group of animals were exposed to the
      same regimen of IH or IA, but in the presence of nonspecific beta-blockade with
      propranolol. Cardiac function was assessed by echocardiography and PV loop
      analyses, and mRNA and protein expression in ventricular homogenates was
      determined. Contrary to our expectations, we found with PV loop analyses that LV
      ejection fraction (63.4 +/- 3.5 vs. 50.5 +/- 2.6%, P = 0.015) and other measures
      of LV contractility were increased in IH-exposed animals compared with IA
      controls. There were no changes in contractile proteins, atrial natriuretic
      peptide levels, LV posterior wall thickness, or heart weight with IH exposure.
      However, cAMP levels were elevated after IH, and propranolol administration
      attenuated the increase in LV contractility induced by IH exposure. We conclude
      that, contrary to our hypothesis, 4 wk of IH exposure in C57BL/6J mice causes an
      increase in LV contractility that occurs independent of ventricular hypertrophy
      and is, in part, mediated by activation of cardiac beta-adrenergic pathways.

PMID- 19589955
TI  - Translational signaling responses preceding resistance training-mediated myofiber
      hypertrophy in young and old humans.
AB  - While skeletal muscle protein accretion during resistance training (RT)-mediated
      myofiber hypertrophy is thought to result from upregulated translation initiation
      signaling, this concept is based on responses to a single bout of unaccustomed
      resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging
      appears to affect acute responses to RE, but whether age differences in
      responsiveness persist during RT leading to impaired RT adaptation is unclear. We
      therefore tested whether muscle protein fractional synthesis rate (FSR) and
      Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE
      differed in old vs. young adults, and whether age differences in acute
      responsiveness were associated with differences in muscle hypertrophy after 16 wk
      of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The
      phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic
      initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all
      elevated (23-199%) 24 h after a bout of unaccustomed RE. A concomitant 62%
      increase in FSR was found in a subset (6 old, 8 young). Age x time interaction
      was found only for RPS6 phosphorylation (+335% in old subjects only), while there
      was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After
      16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength
      were similar in young and old subjects. In conclusion, at the level of
      translational signaling, we found no evidence of impaired responsiveness among
      older adults, and for the first time, we show that changes in translational
      signaling after unaccustomed RE were associated with substantial muscle protein
      accretion (hypertrophy) during continued RT.

PMID- 19589956
TI  - Robust passive dynamics of the musculoskeletal system compensate for unexpected
      surface changes during human hopping.
AB  - When human hoppers are surprised by a change in surface stiffness, they adapt
      almost instantly by changing leg stiffness, implying that neural feedback is not
      necessary. The goal of this simulation study was first to investigate whether leg
      stiffness can change without neural control adjustment when landing on an
      unexpected hard or unexpected compliant (soft) surface, and second to determine
      what underlying mechanisms are responsible for this change in leg stiffness. The
      muscle stimulation pattern of a forward dynamic musculoskeletal model was
      optimized to make the model match experimental hopping kinematics on hard and
      soft surfaces. Next, only surface stiffness was changed to determine how the
      mechanical interaction of the musculoskeletal model with the unexpected surface
      affected leg stiffness. It was found that leg stiffness adapted passively to both
      unexpected surfaces. On the unexpected hard surface, leg stiffness was lower than
      on the soft surface, resulting in close-to-normal center of mass displacement.
      This reduction in leg stiffness was a result of reduced joint stiffness caused by
      lower effective muscle stiffness. Faster flexion of the joints due to the
      interaction with the hard surface led to larger changes in muscle length, while
      the prescribed increase in active state and resulting muscle force remained
      nearly constant in time. Opposite effects were found on the unexpected soft
      surface, demonstrating the bidirectional stabilizing properties of passive
      dynamics. These passive adaptations to unexpected surfaces may be critical when
      negotiating disturbances during locomotion across variable terrain.

PMID- 19589957
TI  - Responses of LDL and HDL particle size and distribution to omega-3 fatty acid
      supplementation and aerobic exercise.
AB  - The purpose of this investigation was to determine the independent and combined
      effects of aerobic exercise and omega-3 fatty acid (n-3fa) supplementation on
      lipid and lipoproteins. Sedentary, normoglycemic, nonsmoking men (n = 11) were
      assigned to perform rest and exercise before and during n-3fa supplementation.
      Exercise consisted of 3 consecutive days of treadmill walking at 65% maximum O(2)
      consumption for 60 min. Supplementation consisted of 42 days of 4.55 g/day of n
      3fa. A two-way factorial ANOVA with repeated measures revealed significant
      reductions in total cholesterol (P = 0.001, -9.2%) and triglyceride (P = 0.007, 
      32.4%) concentrations postexercise. In addition, exercise increased LDL peak
      particle size (P = 0.001) from 26.2 to 26.4 nm, but not HDL size. The n-3fa
      supplementation resulted in a significant shift in the distribution of HDL
      cholesterol (HDL-C) carried by HDL(2b+2a) (P = 0.001, 14.2%) and HDL(3a+3b) (P =
      0.001, -22.8%), despite no significant changes in lipid and lipoprotein
      cholesterol concentrations. The majority of the shift in HDL-C was noted in
      HDL(2b) (P = 0.001, 20.9%) and HDL(3a) (P < 0.001, -31.0%) particles. There were
      no combined effects of exercise and n-3fa supplementation on lipids and
      lipoproteins. Three consecutive days of aerobic exercise reduced triglyceride and
      total cholesterol concentrations with a concomitant increase in LDL peak particle
      size. In contrast, n-3fa supplementation shifted HDL-C from HDL(3) particles to
      HDL(2) particles, despite no significant changes in HDL(2)-C and HDL(3)-C
      concentrations. Exercise and n-3fa supplementation do not synergistically improve
      serum lipids and lipoproteins, but rather independently affect the metabolism of
      lipids and lipoproteins.

PMID- 19589958
TI  - A unique micromechanocalorimeter for simultaneous measurement of heat rate and
      force production of cardiac trabeculae carneae.
AB  - To study cardiac muscle energetics quantitatively, it is of paramount importance
      to measure, simultaneously, mechanical and thermal performance. Ideally, this
      should be achieved under conditions that minimize the risk of tissue anoxia,
      especially under high rates of energy expenditure. In vitro, this consideration
      necessitates the use of preparations of small radial dimensions. To that end, we
      have constructed a unique micromechanocalorimeter, consisting of an open-ended
      flow-through microcalorimeter, a force transducer, and a pair of muscle-length
      actuators. The device enables the metabolic and mechanical performance of cardiac
      trabeculae carneae to be investigated for prolonged periods in a continuously
      replenished oxygen- and nutrient-rich environment.

PMID- 19589959
TI  - Supine and prone differences in regional lung density and pleural pressure
      gradients in the human lung with constant shape.
AB  - The explanation for prone and supine differences in tissue density and pleural
      pressure gradients in the healthy lung has been inferred from several studies as
      compression of dependent tissue by the heart in the supine posture; however, this
      hypothesis has not been directly confirmed. Differences could also arise from
      change in shape of the chest wall and diaphragm, and because of shape with
      respect to gravity. The contribution of this third mechanism is explored here.
      Tissue density and static elastic recoil were estimated in the supine and prone
      left human lung at functional residual capacity using a finite-element analysis.
      Supine model geometries were derived from multidetector row computed tomography
      imaging of two subjects: one normal (subject 1), and one with small airway
      disease (subject 2). For each subject, the prone model was the supine lung shape
      with gravity reversed; therefore, the prone model was isolated from the influence
      of displacement of the diaphragm, chest wall, or heart. Model estimates were
      validated against multidetector row computed tomography measurement of regional
      density for each subject supine and an independent study of the prone and supine
      lung. The magnitude of the gradient in density supine (-4.33%/cm for subject 1,
      and -4.96%/cm for subject 2) was nearly twice as large as for the prone lung (
      2.72%/cm for subject 1, and -2.51%/cm for subject 2), consistent with
      measurements in dogs. The corresponding pleural pressure gradients were 0.54
      cmH(2)O/cm (subject 1) and 0.56 cmH(2)O/cm (subject 2) for supine, and 0.29
      cmH(2)O/cm (subject 1) and 0.27 cmH(2)O/cm (subject 2) for prone. A smaller prone
      gradient was predicted without shape change of the "container" or support of the
      heart by the lung. The influence of the heart was to constrain the shape in which
      the lung deformed.

PMID- 19589960
TI  - Impact of elevated pulmonary blood flow and capillary pressure on lung
      responsiveness.
AB  - Since alterations in pulmonary hemodynamics may lead to airway hyperreactivity,
      the consequences of individual changes in pulmonary blood flow (Qp) and capillary
      pressure (Pc) on lung responsiveness were investigated. During maintenance of a
      steady-state Pc of 5, 10, or 15 mmHg (groups 1-3), acute increases of Qp were
      generated in isolated, perfused rat lungs by simultaneous pulmonary arterial
      pressure elevation and venous pressure lowering. Conversely, at constant low
      (groups 4 and 5) or high Qp (groups 6 and 7), Pc was lowered or elevated by
      changing, in parallel, the pulmonary arterial and venous pressures. Pulmonary
      input impedance was measured under baseline conditions and during methacholine
      provocation (2-18 microg*kg(-1)*min(-1)), whereas the pulmonary hemodynamics were
      altered in accordance with the group allocation. The airway resistance and
      constant-phase parenchymal model parameters were identified from the pulmonary
      input impedance spectra. Increases of Qp at constant Pc had no effect on the
      basal lung mechanics, whereas they enhanced the lung reactivity to methacholine,
      particularly when high Pc was maintained [peak airway resistance increases of 299
      +/- 99% (SE) vs. 609 +/- 217% at Qp levels of 5 and 10 ml/min, respectively, P <
      0.05]. In contrast, the change of Pc at constant Qp slightly deteriorated the
      basal parenchymal mechanics without affecting the lung responsiveness. These
      findings suggest that increases in Qp per se may lead to the development of
      airway hyperreactivity. This phenomenon may contribute to the airway
      susceptibility under conditions associated with simultaneous elevations in
      pulmonary vascular pressures and Qp, such as exercise-induced asthma and the
      situation in children with congenital heart diseases.

PMID- 19589961
TI  - Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed
      muscle protein synthesis at rest and following resistance exercise in young men.
AB  - This study was designed to compare the acute response of mixed muscle protein
      synthesis (MPS) to rapidly (i.e., whey hydrolysate and soy) and slowly (i.e.,
      micellar casein) digested proteins both at rest and after resistance exercise.
      Three groups of healthy young men (n = 6 per group) performed a bout of
      unilateral leg resistance exercise followed by the consumption of a drink
      containing an equivalent content of essential amino acids (10 g) as either whey
      hydrolysate, micellar casein, or soy protein isolate. Mixed MPS was determined by
      a primed constant infusion of l-[ring-(13)C(6)]phenylalanine. Ingestion of whey
      protein resulted in a larger increase in blood essential amino acid, branched
      chain amino acid, and leucine concentrations than either casein or soy (P <
      0.05). Mixed MPS at rest (determined in the nonexercised leg) was higher with
      ingestion of faster proteins (whey = 0.091 +/- 0.015, soy = 0.078 +/- 0.014,
      casein = 0.047 +/- 0.008%/h); MPS after consumption of whey was approximately 93%
      greater than casein (P < 0.01) and approximately 18% greater than soy (P =
      0.067). A similar result was observed after exercise (whey > soy > casein); MPS
      following whey consumption was approximately 122% greater than casein (P < 0.01)
      and 31% greater than soy (P < 0.05). MPS was also greater with soy consumption at
      rest (64%) and following resistance exercise (69%) compared with casein (both P <
      0.01). We conclude that the feeding-induced simulation of MPS in young men is
      greater after whey hydrolysate or soy protein consumption than casein both at
      rest and after resistance exercise; moreover, despite both being fast proteins,
      whey hydrolysate stimulated MPS to a greater degree than soy after resistance
      exercise. These differences may be related to how quickly the proteins are
      digested (i.e., fast vs. slow) or possibly to small differences in leucine
      content of each protein.

PMID- 19589962
TI  - Flexible learning of multiple speech structures in bilingual infants.
AB  - Children acquire their native language according to a well-defined time frame.
      Surprisingly, although children raised in bilingual environments have to learn
      roughly twice as much about language as their monolingual peers, the speed of
      acquisition is comparable in monolinguals and bilinguals. Here, we show that
      preverbal 12-month-old bilingual infants have become more flexible at learning
      speech structures than monolinguals. When given the opportunity to simultaneously
      learn two different regularities, bilingual infants learned both, whereas
      monolinguals learned only one of them. Hence, bilinguals may acquire two
      languages in the time in which monolinguals acquire one because they quickly
      become more flexible learners.

PMID- 19589963
TI  - Pre-target axon sorting establishes the neural map topography.
AB  - Sensory information detected by the peripheral nervous system is represented as a
      topographic map in the brain. It has long been thought that the topography of the
      map is determined by graded positional cues that are expressed by the target.
      Here, we analyzed the pre-target axon sorting for olfactory map formation in
      mice. In olfactory sensory neurons, an axon guidance receptor, Neuropilin-1, and
      its repulsive ligand, Semaphorin-3A, are expressed in a complementary manner. We
      found that expression levels of Neuropilin-1 determined both pre-target sorting
      and projection sites of axons. Olfactory sensory neuron-specific knockout of
      Semaphorin-3A perturbed axon sorting and altered the olfactory map topography.
      Thus, pre-target axon sorting plays an important role in establishing the
      topographic order based on the relative levels of guidance molecules expressed by
      axons.

PMID- 19589964
TI  - The formation of Population III binaries from cosmological initial conditions.
AB  - Previous high-resolution cosmological simulations predicted that the first stars
      to appear in the early universe were very massive and formed in isolation. Here,
      we discuss a cosmological simulation in which the central 50 M(o) (where M(o) is
      the mass of the Sun) clump breaks up into two cores having a mass ratio of two to
      one, with one fragment collapsing to densities of 10(-8) grams per cubic
      centimeter. The second fragment, at a distance of approximately 800 astronomical
      units, is also optically thick to its own cooling radiation from molecular
      hydrogen lines but is still able to cool via collision-induced emission. The two
      dense peaks will continue to accrete from the surrounding cold gas reservoir over
      a period of approximately 10(5) years and will likely form a binary star system.

PMID- 19589967
TI  - Science in the future of India.

PMID- 19589965
TI  - Dependence of mouse embryonic stem cells on threonine catabolism.
AB  - Measurements of the abundance of common metabolites in cultured embryonic stem
      (ES) cells revealed an unusual state with respect to one-carbon metabolism. These
      findings led to the discovery of copious expression of the gene encoding
      threonine dehydrogenase (TDH) in ES cells. TDH-mediated catabolism of threonine
      takes place in mitochondria to generate glycine and acetyl-coenzyme A (CoA), with
      glycine facilitating one-carbon metabolism via the glycine cleavage system and
      acetyl-CoA feeding the tricarboxylic acid cycle. Culture media individually
      deprived of each of the 20 amino acids were applied to ES cells, leading to the
      discovery that ES cells are critically dependent on one amino acid--threonine.
      These observations show that ES cells exist in a high-flux backbone metabolic
      state comparable to that of rapidly growing bacterial cells.

PMID- 19589966
TI  - Positive selection of tyrosine loss in metazoan evolution.
AB  - John Nash showed that within a complex system, individuals are best off if they
      make the best decision that they can, taking into account the decisions of the
      other individuals. Here, we investigate whether similar principles influence the
      evolution of signaling networks in multicellular animals. Specifically, by
      analyzing a set of metazoan species we observed a striking negative correlation
      of genomically encoded tyrosine content with biological complexity (as measured
      by the number of cell types in each organism). We discuss how this observed
      tyrosine loss correlates with the expansion of tyrosine kinases in the evolution
      of the metazoan lineage and how it may relate to the optimization of signaling
      systems in multicellular animals. We propose that this phenomenon illustrates
      genome-wide adaptive evolution to accommodate beneficial genetic perturbation.

PMID- 19589968
TI  - Energy. DOE's push to train a new generation falters in House.

PMID- 19589969
TI  - Biomedical research. Researchers generally happy with final stem cell rules.

PMID- 19589970
TI  - Opinion polls. An inside/outside view of U.S. science.

PMID- 19589972
TI  - Newsmaker interview. Hughes's Tjian holds to a 'global' standard of merit.
      Interview by Jocelyn Kaiser.

PMID- 19589974
TI  - Scientific community. Resignations highlight disagreement on vaccines in autism
      group.

PMID- 19589975
TI  - Paleoanthropology. Bringing hominins back to life.

PMID- 19589976
TI  - Paleoanthropology. Evolving artists.

PMID- 19589977
TI  - Pandemic influenza. Straight from the pig's mouth: swine research with swine
      influenzas.

PMID- 19589978
TI  - Genetics. Genomic clues to DNA treasure sometimes lead nowhere.

PMID- 19589979
TI  - Immunology. Take-charge B cells create a buzz.

PMID- 19589981
TI  - A standardized response to biological invasions.

PMID- 19589982
TI  - Saving African lions.

PMID- 19589983
TI  - Neuroscientists need neuroethics teaching.

PMID- 19589984
TI  - Comment on "DNA from pre-Clovis human coprolites in Oregon, North America".
AB  - Gilbert et al. (Reports, 9 May 2008, p. 786) presented DNA analysis of coprolites
      recovered from an Oregon cave as evidence for a human presence in North America
      before the Clovis culture. Results of our micromorphological and Fourier
      transform infrared spectroscopy analyses of one of the reported coprolites are
      difficult to reconcile with the DNA results identifying the coprolite as human.

PMID- 19589985
TI  - Comment on "DNA from pre-Clovis human coprolites in Oregon, North America".
AB  - Gilbert et al. (Reports, 9 May 2008, p. 786) analyzed DNA from radiocarbon-dated
      paleofecal remains from Paisley Cave, Oregon, which ostensibly demonstrate a
      human presence in North America predating the well-established Clovis complex. We
      question the authenticity of their DNA results and argue that in the absence of
      intact stratigraphy and diagnostic artifacts, and in view of carbon isotope
      anomalies, the radiocarbon dates of the oldest specimens are unreliable.

PMID- 19589987
TI  - Atmosphere. Smoke and climate change.

PMID- 19589986
TI  - Energy. Nuclear waste management in the United States--starting over.

PMID- 19589988
TI  - Evolution. How did the turtle get its shell?

PMID- 19589989
TI  - Astronomy. Sunspot flows and filaments.

PMID- 19589990
TI  - Materials science. Predicting fatigue failures.

PMID- 19589991
TI  - Cell biology. Sizing up the cell.

PMID- 19589992
TI  - Materials science. Oriented assembly of metamaterials.

PMID- 19589993
TI  - Drug discovery and natural products: end of an era or an endless frontier?
AB  - Historically, the majority of new drugs have been generated from natural products
      (secondary metabolites) and from compounds derived from natural products. During
      the past 15 years, pharmaceutical industry research into natural products has
      declined, in part because of an emphasis on high-throughput screening of
      synthetic libraries. Currently there is substantial decline in new drug approvals
      and impending loss of patent protection for important medicines. However,
      untapped biological resources, "smart screening" methods, robotic separation with
      structural analysis, metabolic engineering, and synthetic biology offer exciting
      technologies for new natural product drug discovery. Advances in rapid genetic
      sequencing, coupled with manipulation of biosynthetic pathways, may provide a
      vast resource for the future discovery of pharmaceutical agents.

PMID- 19589994
TI  - Traction on immobilized netrin-1 is sufficient to reorient axons.
AB  - During embryonic development, axons are guided to their target by patterning
      proteins encountered along their trajectory. These cues can be linked to the
      cells that produce them or secreted into the extracellular matrix. Whether
      secreted cues, like netrin-1, provide traction for the growth cone when they
      become attached to the extracellular matrix is unclear. Advancing spinal
      commissural neuron growth cones were shown to generate local forces of 4 to 15
      piconewtons but, when confronted with immobilized netrin-1, generated traction
      forces in excess of 63 piconewtons on netrin-1 that can redirect the trajectory
      of the axon.

PMID- 19589996
TI  - Quantum walk in position space with single optically trapped atoms.
AB  - The quantum walk is the quantum analog of the well-known random walk, which forms
      the basis for models and applications in many realms of science. Its properties
      are markedly different from the classical counterpart and might lead to extensive
      applications in quantum information science. In our experiment, we implemented a
      quantum walk on the line with single neutral atoms by deterministically
      delocalizing them over the sites of a one-dimensional spin-dependent optical
      lattice. With the use of site-resolved fluorescence imaging, the final wave
      function is characterized by local quantum state tomography, and its spatial
      coherence is demonstrated. Our system allows the observation of the quantum-to
      classical transition and paves the way for applications, such as quantum cellular
      automata.

PMID- 19589995
TI  - Cell growth and size homeostasis in proliferating animal cells.
AB  - A long-standing question in biology is whether there is an intrinsic mechanism
      for coordinating growth and the cell cycle in metazoan cells. We examined cell
      size distributions in populations of lymphoblasts and applied a mathematical
      analysis to calculate how growth rates vary with both cell size and the cell
      cycle. Our results show that growth rate is size-dependent throughout the cell
      cycle. After initial growth suppression, there is a rapid increase in growth rate
      during the G1 phase, followed by a period of constant exponential growth. The
      probability of cell division varies independently with cell size and cell age. We
      conclude that proliferating mammalian cells have an intrinsic mechanism that
      maintains cell size.

PMID- 19589997
TI  - Dynamics of chemical bonding mapped by energy-resolved 4D electron microscopy.
AB  - Chemical bonding dynamics are fundamental to the understanding of properties and
      behavior of materials and molecules. Here, we demonstrate the potential of time
      resolved, femtosecond electron energy loss spectroscopy (EELS) for mapping
      electronic structural changes in the course of nuclear motions. For graphite, it
      is found that changes of milli-electron volts in the energy range of up to 50
      electron volts reveal the compression and expansion of layers on the subpicometer
      scale (for surface and bulk atoms). These nonequilibrium structural features are
      correlated with the direction of change from sp2 [two-dimensional (2D) graphene]
      to sp3 (3D-diamond) electronic hybridization, and the results are compared with
      theoretical charge-density calculations. The reported femtosecond time resolution
      of four-dimensional (4D) electron microscopy represents an advance of 10 orders
      of magnitude over that of conventional EELS methods.

PMID- 19589999
TI  - Nonvolcanic tremor evolution and the San Simeon and Parkfield, California,
      earthquakes.
AB  - Nonvolcanic tremors occur adjacent to locked faults and may be closely related to
      the generation of earthquakes. Monitoring of the San Andreas Fault in the
      Parkfield, California, region revealed that after two strong earthquakes, tremor
      activity increased in a nearly dormant tremor zone, increased and became periodic
      in a previously active zone, and has remained elevated and periodic for over 4
      years. Static shear- and Coulomb-stress increases of 6 to 14 kilopascals from
      these two earthquakes are coincident with sudden increases in tremor rates. The
      persistent changes in tremor suggest that stress is now accumulating more rapidly
      beneath this part of the San Andreas Fault, which ruptured in the moment
      magnitude 7.8 Ft. Tejon earthquake of 1857.

PMID- 19589998
TI  - Manganese- and iron-dependent marine methane oxidation.
AB  - Anaerobic methanotrophs help regulate Earth's climate and may have been an
      important part of the microbial ecosystem on the early Earth. The anaerobic
      oxidation of methane (AOM) is often thought of as a sulfate-dependent process,
      despite the fact that other electron acceptors are more energetically favorable.
      Here, we show that microorganisms from marine methane-seep sediment in the Eel
      River Basin in California are capable of using manganese (birnessite) and iron
      (ferrihydrite) to oxidize methane, revealing that marine AOM is coupled, either
      directly or indirectly, to a larger variety of oxidants than previously thought.
      Large amounts of manganese and iron are provided to oceans from rivers,
      indicating that manganese- and iron-dependent AOM have the potential to be
      globally important.

PMID- 19590000
TI  - Evolution of the turtle body plan by the folding and creation of new muscle
      connections.
AB  - The turtle shell offers a fascinating case study of vertebrate evolution, based
      on the modification of a common body plan. The carapace is formed from ribs,
      which encapsulate the scapula; this stands in contrast to the typical amniote
      body plan and serves as a key to understanding turtle evolution. Comparative
      analyses of musculoskeletal development between the Chinese soft-shelled turtle
      and other amniotes revealed that initial turtle development conforms to the
      amniote pattern; however, during embryogenesis, lateral rib growth results in a
      shift of elements. In addition, some limb muscles establish new turtle-specific
      attachments associated with carapace formation. We propose that the evolutionary
      origin of the turtle body plan results from heterotopy based on folding and novel
      connectivities.

PMID- 19590001
TI  - Caloric restriction delays disease onset and mortality in rhesus monkeys.
AB  - Caloric restriction (CR), without malnutrition, delays aging and extends life
      span in diverse species; however, its effect on resistance to illness and
      mortality in primates has not been clearly established. We report findings of a
      20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this
      critical gap in aging research. In a population of rhesus macaques maintained at
      the Wisconsin National Primate Research Center, moderate CR lowered the incidence
      of aging-related deaths. At the time point reported, 50% of control fed animals
      survived as compared with 80% of the CR animals. Furthermore, CR delayed the
      onset of age-associated pathologies. Specifically, CR reduced the incidence of
      diabetes, cancer, cardiovascular disease, and brain atrophy. These data
      demonstrate that CR slows aging in a primate species.

PMID- 19590002
TI  - Discovery of swine as a host for the Reston ebolavirus.
AB  - Since the discovery of the Marburg and Ebola species of filovirus, seemingly
      random, sporadic fatal outbreaks of disease in humans and nonhuman primates have
      given impetus to identification of host tropisms and potential reservoirs.
      Domestic swine in the Philippines, experiencing unusually severe outbreaks of
      porcine reproductive and respiratory disease syndrome, have now been discovered
      to host Reston ebolavirus (REBOV). Although REBOV is the only member of
      Filoviridae that has not been associated with disease in humans, its emergence in
      the human food chain is of concern. REBOV isolates were found to be more
      divergent from each other than from the original virus isolated in 1989,
      indicating polyphyletic origins and that REBOV has been circulating since, and
      possibly before, the initial discovery of REBOV in monkeys.

PMID- 19590003
TI  - Induction of synaptic long-term potentiation after opioid withdrawal.
AB  - mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment
      of severe pain but may paradoxically also enhance pain sensitivity, that is, lead
      to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR
      agonists induces long-term potentiation (LTP) at the first synapse in pain
      pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of
      heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate
      receptors and a rise of postsynaptic calcium concentrations. In contrast, the
      acute depression by opioids is induced presynaptically at these synapses.
      Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and
      signal transduction pathways with OIH. These findings provide a previously
      unrecognized target to selectively combat pro-nociceptive effects of opioids
      without compromising opioid analgesia.

PMID- 19590005
TI  - Hematopoietic cytokines can instruct lineage choice.
AB  - The constant regeneration of the blood system during hematopoiesis requires
      tightly controlled lineage decisions of hematopoietic progenitor cells (HPCs).
      Because of technical limitations, differentiation of individual HPCs could not
      previously be analyzed continuously. It was therefore disputed whether cell
      extrinsic cytokines can instruct HPC lineage choice or only allow survival of
      cells that are already lineage-restricted. Here, we used bioimaging approaches
      that allow the continuous long-term observation of individual differentiating
      mouse HPCs. We demonstrate that the physiological cytokines, macrophage colony
      stimulating factor and granulocyte colony-stimulating factor, can instruct
      hematopoietic lineage choice.

PMID- 19590004
TI  - A functional role for adult hippocampal neurogenesis in spatial pattern
      separation.
AB  - The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate
      pattern separation-the formation of distinct and orthogonal representations of
      mnemonic information-and also undergoes neurogenesis throughout life. How
      neurogenesis contributes to hippocampal function is largely unknown. Using adult
      mice in which hippocampal neurogenesis was ablated, we found specific impairments
      in spatial discrimination with two behavioral assays: (i) a spatial navigation
      radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse
      touch screen. Mice with ablated neurogenesis were impaired when stimuli were
      presented with little spatial separation, but not when stimuli were more widely
      separated in space. Thus, newborn neurons may be necessary for normal pattern
      separation function in the DG of adult mice.

PMID- 19590007
TI  - Automated multidimensional phenotypic profiling using large public microarray
      repositories.
AB  - Phenotypes are complex, and difficult to quantify in a high-throughput fashion.
      The lack of comprehensive phenotype data can prevent or distort genotype
      phenotype mapping. Here, we describe "PhenoProfiler," a computational method that
      enables in silico phenotype profiling. Drawing on the principle that similar gene
      expression patterns are likely to be associated with similar phenotype patterns,
      PhenoProfiler supplements the missing quantitative phenotype information for a
      given microarray dataset based on other well-characterized microarray datasets.
      We applied our method to 587 human microarray datasets covering >14,000 samples,
      and confirmed that the predicted phenotype profiles are highly consistent with
      true phenotype descriptions. PhenoProfiler offers several unique capabilities:
      (i) automated, multidimensional phenotype profiling, facilitating the analysis
      and treatment design of complex diseases; (ii) the extrapolation of phenotype
      profiles beyond provided classes; and (iii) the detection of confounding
      phenotype factors that could otherwise bias biological inferences. Finally,
      because no direct comparisons are made between gene expression values from
      different datasets, the method can use the entire body of cross-platform
      microarray data. This work has produced a compendium of phenotype profiles for
      the National Center for Biotechnology Information GEO datasets, which can
      facilitate an unbiased understanding of the transcriptome-phenome mapping. The
      continued accumulation of microarray data will further increase the power of
      PhenoProfiler, by increasing the variety and the quality of phenotypes to be
      profiled.

PMID- 19590008
TI  - Biosynthesis of the salinosporamide A polyketide synthase substrate
      chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine.
AB  - Polyketides are among the major classes of bioactive natural products used to
      treat microbial infections, cancer, and other diseases. Here we describe a
      pathway to chloroethylmalonyl-CoA as a polyketide synthase building block in the
      biosynthesis of salinosporamide A, a marine microbial metabolite whose chlorine
      atom is crucial for potent proteasome inhibition and anticancer activity. S
      adenosyl-L-methionine (SAM) is converted to 5'-chloro-5'-deoxyadenosine (5'-ClDA)
      in a reaction catalyzed by a SAM-dependent chlorinase as previously reported. By
      using a combination of gene deletions, biochemical analyses, and chemical
      complementation experiments with putative intermediates, we now provide evidence
      that 5'-ClDA is converted to chloroethylmalonyl-CoA in a 7-step route via the
      penultimate intermediate 4-chlorocrotonyl-CoA. Because halogenation often
      increases the bioactivity of drugs, the availability of a halogenated polyketide
      building block may be useful in molecular engineering approaches toward
      polyketide scaffolds.

PMID- 19590010
TI  - Notch pathway regulation of chondrocyte differentiation and proliferation during
      appendicular and axial skeleton development.
AB  - The role of Notch signaling in cartilage differentiation and maturation in vivo
      was examined. Conditional Notch pathway gain and loss of function was achieved
      using a Cre/loxP approach to manipulate Notch signaling in cartilage precursors
      and chondrocytes of the developing mouse embryo. Conditional overexpression of
      activated Notch intracellular domain (NICD) in the chondrocyte lineage results in
      skeletal malformations with decreased cartilage precursor proliferation and
      inhibited hypertrophic chondrocyte differentiation. Likewise, expression of NICD
      in cartilage precursors inhibits sclerotome differentiation, resulting in severe
      axial skeleton abnormalities. Furthermore, conditional loss of Notch signaling
      via RBP-J gene deletion in the chondrocyte lineage results in increased
      chondrocyte proliferation and skeletal malformations consistent with the observed
      increase in hypertrophic chondrocytes. In addition, the Notch pathway inhibits
      expression of Sox9 and its target genes required for normal chondrogenic cell
      proliferation and differentiation. Together, our results demonstrate that
      appropriate Notch pathway signaling is essential for proper chondrocyte
      progenitor proliferation and for the normal progression of hypertrophic
      chondrocyte differentiation into bone in the developing appendicular and axial
      skeletal elements.

PMID- 19590009
TI  - Identification of the functional core of the influenza A virus A/M2 proton
      selective ion channel.
AB  - The influenza A virus M2 protein (A/M2) is a homotetrameric pH-activated proton
      transporter/channel that mediates acidification of the interior of endosomally
      encapsulated virus. This 97-residue protein has a single transmembrane (TM)
      helix, which associates to form homotetramers that bind the anti-influenza drug
      amantadine. However, the minimal fragment required for assembly and proton
      transport in cellular membranes has not been defined. Therefore, the conductance
      properties of truncation mutants expressed in Xenopus oocytes were examined. A
      short fragment spanning residues 21-61, M2(21-61), was inserted into the
      cytoplasmic membrane and had specific, amantadine-sensitive proton transport
      activity indistinguishable from that of full-length A/M2; an epitope-tagged
      version of an even shorter fragment, M2(21-51)-FLAG, had specific activity within
      a factor of 2 of the full-length protein. Furthermore, synthetic fragments
      including a peptide spanning residues 22-46 were found to transport protons into
      liposomes in an amantadine-sensitive manner. In addition, the functionally
      important His-37 residue pK(a) values are highly perturbed in the tetrameric form
      of the protein, a property conserved in the TM peptide and full-length A/M2 in
      both micelles and bilayers. These data demonstrate that the determinants for
      folding, drug binding, and proton translocation are packaged in a remarkably
      small peptide that can now be studied with confidence.

PMID- 19590011
TI  - Retraction for "S1P3 receptor-induced reorganization of epithelial tight
      junctions compromises lung barrier integrity and is potentiated by TNF".

PMID- 19590012
TI  - A single modular serine protease integrates signals from pattern-recognition
      receptors upstream of the Drosophila Toll pathway.
AB  - The Drosophila Toll receptor does not interact directly with microbial
      determinants, but is instead activated by a cleaved form of the cytokine-like
      molecule Spatzle. During the immune response, Spatzle is processed by complex
      cascades of serine proteases, which are activated by secreted pattern-recognition
      receptors. Here, we demonstrate the essential role of ModSP, a modular serine
      protease, in the activation of the Toll pathway by gram-positive bacteria and
      fungi. Our analysis shows that ModSP integrates signals originating from the
      circulating recognition molecules GNBP3 and PGRP-SA and connects them to the
      Grass-SPE-Spatzle extracellular pathway upstream of the Toll receptor. It also
      reveals the conserved role of modular serine proteases in the activation of
      insect immune reactions.

PMID- 19590013
TI  - Channelrhodopsin-2 is a leaky proton pump.
AB  - Since its discovery, the light-gated cation channel Channelrhodopsin-2 (ChR2) has
      proven to be a long-sought tool for the noninvasive, light-activated control of
      neural cells in culture and in living animals. Although ChR2 is widely used in
      neurobiological applications, little is known about its molecular mechanism. In
      this work, the unitary conductance of ChR2 was determined for different cations,
      for example 40 fS at 200 mM NaCl and -60 mV, using noise analysis. The kinetics
      of the ion channel obtained by noise analysis is in excellent agreement with the
      photocurrent kinetics obtained by voltage-clamp and time-resolved spectroscopy.
      The inward rectification of the channel could be explained by the single channel
      parameters. ChR2 represents an ion channel with a 7 transmembrane helix motif,
      even though the sequence homology of its essential amino acids to those of the
      light-driven H(+) pump bacteriorhodopsin (bR) is high. Here, we also show that
      when ChR2 is expressed in electrofused giant HEK293 cells or reconstituted on
      planar lipid membranes, it can indeed act as an outwardly driven H(+) pump,
      demonstrating that ChR2 is bifunctional, and in-line with other microbial
      rhodopsins, a H(+) pump but with a leak that shows ion channel properties.

PMID- 19590014
TI  - Structure of the core editing complex (L-complex) involved in uridine
      insertion/deletion RNA editing in trypanosomatid mitochondria.
AB  - Uridine insertion/deletion RNA editing is a unique form of posttranscriptional
      RNA processing that occurs in mitochondria of kinetoplastid protists. We have
      carried out 3D structural analyses of the core editing complex or "L (ligase)
      complex" from Leishmania tarentolae mitochondria isolated by the tandem affinity
      purification procedure (TAP). The purified material, sedimented at 20-25S,
      migrated in a blue native gel at 1 MDa and exhibited both precleaved and full
      cycle gRNA-mediated U-insertion and U-deletion in vitro activities. The purified
      L-complex was analyzed by electron tomography to determine the extent of
      heterogeneity. Three-dimensional structural comparisons of individual particles
      in the tomograms revealed that a majority of the complexes have a similar shape
      of a slender triangle. An independent single-particle reconstruction, using a
      featureless Gaussian ball as the initial model, converged to a similar triangular
      structure. Another single-particle reconstruction, using the averaged tomography
      structure as the initial model, yielded a similar structure. The REL1 ligase was
      localized on the model to the base of the apex by decoration with REL1-specific
      IgG. This structure should prove useful for a detailed analysis of the editing
      reaction.

PMID- 19590015
TI  - Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a
      protein serine/threonine phosphatase to activate ASK1.
AB  - Phosphoglycerate mutase (PGAM) is an enzyme of intermediary metabolism that
      converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. Here, we
      discovered PGAM5 that is anchored in the mitochondrial membrane lacks PGAM
      activity and instead associates with the MAP kinase kinase kinase ASK1 and acts
      as a specific protein Ser/Thr phosphatase that activates ASK1 by
      dephosphorylation of inhibitory sites. Mutation of an active site His-105 in
      PGAM5 abolished phosphatase activity with ASK1 and phospho-Thr peptides as
      substrates. The Drosophila and Caenorhabditis elegans orthologs of PGAM5 also
      exhibit specific Ser/Thr phosphatase activity and activate the corresponding
      Drosophila and C. elegans ASK1 kinases. PGAM5 is unrelated to the other known
      Ser/Thr phosphatases of the PPP, MPP, and FCP families, and our results suggest
      that this member of the PGAM family has crossed over from small molecules to
      protein substrates and been adapted to serve as a specialized activator of ASK1.

PMID- 19590016
TI  - The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during
      early embryonic cell cycles.
AB  - Competency for DNA replication is functionally coupled to the activation of
      histone gene expression at the onset of S phase to form chromatin. Human histone
      nuclear factor P (HiNF-P; gene symbol HINFP) bound to its cyclin E/cyclin
      dependent kinase 2 (CDK2) responsive coactivator p220(NPAT) is a key regulator of
      multiple human histone H4 genes that encode a major subunit of the nucleosome.
      Induction of the histone H4 transcription factor (HINFP)/p220(NPAT) coactivation
      complex occurs in parallel with the CDK-dependent release of pRB from E2F at the
      restriction point. Here, we show that the downstream CDK-dependent cell cycle
      effector HINFP is genetically required and, in contrast to the CDK2/cyclin E
      complex, cannot be compensated. We constructed a mouse Hinfp-null mutation and
      found that heterozygous Hinfp mice survive, indicating that 1 allele suffices for
      embryogenesis. Homozygous loss-of-function causes embryonic lethality: No
      homozygous Hinfp-null mice are obtained at or beyond embryonic day (E) 6.5. In
      blastocyst cultures, Hinfp-null embryos exhibit a delay in hatching, abnormal
      growth, and loss of histone H4 gene expression. Our data indicate that the
      CDK2/cyclin E/p220(NPAT)/HINFP/histone gene signaling pathway at the G1/S phase
      transition is an essential, nonredundant cell cycle regulatory mechanism that is
      established early in embryogenesis.

PMID- 19590019
TI  - Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a
      randomized, double-blind, placebo-controlled, parallel-group clinical trial.
AB  - RATIONALE: Asthma exacerbations are unpredictable, disruptive, and frightening,
      and are therefore important to prevent. OBJECTIVES: We investigated whether a
      policy of quadrupling the dose of inhaled corticosteroid when asthma control
      starts to deteriorate reduces asthma exacerbations requiring treatment with oral
      corticosteroids. METHODS: A total of 403 people with asthma were given a self
      management plan and randomized to take an active or placebo corticosteroid
      inhaler in addition to their usual asthma treatment when their PEF fell by 15% on
      2 consecutive days or by 30% on 1 day. The study inhalers provided a quadrupling
      or no change in corticosteroid dose. MEASUREMENTS AND MAIN RESULTS: Eighteen of
      197 (9%) and 29 of 203 (14%) participants had an exacerbation of asthma requiring
      treatment with oral corticosteroids in the active and placebo groups,
      respectively, giving a risk ratio of 0.64 (95% confidence interval, 0.37-1.11, P
      = 0.11). Of the 94 participants who started the study inhaler far fewer required
      treatment with oral corticosteroids in the active compared with the placebo
      group: 12 of 56 (21%) in the active group and 19 of 38 (50%) in the placebo
      group, giving a risk ratio of 0.43 (95% confidence interval, 0.24-0.78, P =
      0.004). CONCLUSIONS: Although our primary outcome did not reach statistical
      significance, quadrupling the dose of inhaled corticosteroid when asthma control
      starts to deteriorate appears to reduce acute exacerbations of asthma and
      deserves further investigation. Clinical trial registered with www.controlled
      trials.com (ISRCTN 46018181).

PMID- 19590017
TI  - The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron
      microscopy.
AB  - Infection with the hepatitis C virus (HCV) has a huge impact on global health
      putting more than 170 million people at risk of developing severe liver disease.
      The HCV encoded p7 ion channel is essential for the production of infectious
      viruses. Despite a growing body of functional data, little is known about the 3
      dimensional (3D) structure of the channel. Here, we present the 3D structure of a
      full-length viroporin, the detergent-solubilized hexameric 42 kDa form of the HCV
      p7 ion channel, as determined by single-particle electron microscopy using the
      random conical tilting approach. The reconstruction of such a small protein
      complex was made possible by a combination of high-contrast staining, the
      symmetry, and the distinct structural features of the channel. The orientation of
      the p7 monomers within the density was established using immunolabeling with N
      and C termini specific F(ab) fragments. The density map at a resolution of
      approximately 16 A reveals a flower-shaped protein architecture with protruding
      petals oriented toward the ER lumen. This broadest part of the channel presents a
      comparatively large surface area providing potential interaction sites for
      cellular and virally encoded ER resident proteins.

PMID- 19590020
TI  - Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of
      tuberculosis: a Tuberculosis Network European Trialsgroup study.
AB  - RATIONALE: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when
      acid fast bacilli (AFB) cannot be detected in sputum smears. OBJECTIVES:
      Following a proof of principle study, we examined in routine clinical practice
      whether individuals with sputum AFB smear-negative TB can be discriminated from
      those with latent TB infection by local immunodiagnosis with a Mycobacterium
      tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. METHODS: Subjects
      suspected of having active TB who were unable to produce sputum or with AFB
      negative sputum smears were prospectively enrolled at Tuberculosis Network
      European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic
      target-6 and culture-filtrate-protein-10 peptides was performed on peripheral
      blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells
      (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was
      performed on bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Seventy
      one of 347 (20.4%) patients had active TB. Out of 276 patients who had an
      alternative diagnosis, 127 (46.0%) were considered to be latently infected with
      M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and
      specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and
      80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was
      superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M.
      tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB.
      In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not
      influenced by previous history of TB. CONCLUSIONS: Bronchoalveolar lavage ELISpot
      is an important advancement to rapidly distinguish sputum AFB smear-negative TB
      from latent TB infection in routine clinical practice.

PMID- 19590021
TI  - Randomized trial of a decision aid for patients with cystic fibrosis considering
      lung transplantation.
AB  - RATIONALE: We developed an evidence-based decision aid for patients with advanced
      cystic fibrosis considering referral for lung transplantation. OBJECTIVES: To
      prospectively evaluate whether use of the decision aid increased knowledge about
      the options, improved realistic expectations, and decreased decisional conflict
      in adult patients. METHODS: We performed a single-blind randomized controlled
      trial involving 149 adult patients with cystic fibrosis with an FEV(1) <or= 40%
      predicted from 14 Canadian and Australian centers. All participants received an
      education and counseling session from their cystic fibrosis team and were then
      randomized to receive the decision aid or usual care. The decision aid is
      available online at http://decisionaid.ohri.ca/decaids.html. MEASUREMENTS AND
      MAIN RESULTS: The primary end points measured were participants' knowledge,
      realistic expectations, and decisional conflict evaluated 3 weeks after
      randomization. Patients randomized to the decision aid had greater knowledge
      about their options (P < 0.0001) and had more realistic expectations about the
      benefits and risks of lung transplantation (P < 0.0001) compared with those
      randomized to usual care. The total decisional conflict score was significantly
      lower in the decision aid group 3 weeks postrandomization compared with the usual
      care group (11.6 vs. 20.4; P = 0.0007). Decisions were durable; 88% of patients
      in the decision aid group and 75% in the usual care group maintained the same
      choice 12 months after randomization (P = 0.06). CONCLUSIONS: Use of a decision
      aid for patients with cystic fibrosis considering referral for lung
      transplantation, in addition to usual education and counseling, improves patient
      knowledge, realistic expectations, decisional conflict, and patient satisfaction.
      Clinical trial registered with www.clinicaltrials.gov (NCT00345449).

PMID- 19590022
TI  - Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated
      immunosuppression: a double-blind, randomized, placebo-controlled multicenter
      trial.
AB  - RATIONALE: Sustained sepsis-associated immunosuppression is associated with
      uncontrolled infection, multiple organ dysfunction, and death. OBJECTIVES: In the
      first controlled biomarker-guided immunostimulatory trial in sepsis, we tested
      whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses
      monocyte deactivation, a hallmark of sepsis-associated immunosuppression (primary
      endpoint), and improves the immunological and clinical course of patients with
      sepsis. METHODS: In a prospective, randomized, double-blind, placebo-controlled,
      multicenter trial, 38 patients (19/group) with severe sepsis or septic shock and
      sepsis-associated immunosuppression (monocytic HLA-DR [mHLA-DR] <8,000 monoclonal
      antibodies (mAb) per cell for 2 d) were treated with GM-CSF (4 microg/kg/d) or
      placebo for 8 days. The patients' clinical and immunological course was followed
      up for 28 days. MEASUREMENTS AND MAIN RESULTS: Both groups showed comparable
      baseline mHLA-DR levels (5,609 +/- 3,628 vs. 5,659 +/- 3,332 mAb per cell), which
      significantly increased within 24 hours in the GM-CSF group. After GM-CSF
      treatment, mHLA-DR was normalized in 19/19 treated patients, whereas this
      occurred in 3/19 control subjects only (P < 0.001). GM-CSF also restored ex-vivo
      Toll-like receptor 2/4-induced proinflammatory monocytic cytokine production. In
      patients receiving GM-CSF, a shorter time of mechanical ventilation (148 +/- 103
      vs. 207 +/- 58 h, P = 0.04), an improved Acute Physiology and Chronic Health
      Evaluation-II score (P = 0.02), and a shorter length of both intrahospital and
      intensive care unit stay was observed (59 +/- 33 vs. 69 +/- 46 and 41 +/- 26 vs.
      52 +/- 39 d, respectively, both not significant). Side effects related to the
      intervention were not noted. CONCLUSIONS: Biomarker-guided GM-CSF therapy in
      sepsis is safe and effective for restoring monocytic immunocompetence. Use of GM
      CSF may shorten the time of mechanical ventilation and hospital/intensive care
      unit stay. A multicenter trial powered for the improvement of clinical parameters
      and mortality as primary endpoints seems indicated. Clinical trial registered
      with www.clinicaltrials.gov (NCT00252915).

PMID- 19590023
TI  - Macrophage tumor necrosis factor-alpha induces epithelial expression of
      granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial
      repair.
AB  - RATIONALE: Resident alveolar macrophages have been attributed a crucial role in
      host defense toward pulmonary infection. Their contribution to alveolar repair
      processes, however, remains elusive. OBJECTIVES: We investigated whether
      activated resident alveolar macrophages contribute to alveolar epithelial repair
      on lipopolysaccharide (LPS) challenge in vitro and in vivo and analyzed the
      molecular interaction pathways involved. METHODS: We evaluated macrophage
      epithelial cross-talk mediators for epithelial cell proliferation in an in vitro
      coculture system and an in vivo model of LPS-induced acute lung injury comparing
      wild-type, granulocyte-macrophage colony-stimulating factor (GM-CSF)-deficient
      (GM(-/-)), and human SPC-GM mice (GM(-/-) mice expressing an SPC-promotor
      regulated GM-CSF transgene). MEASUREMENTS AND MAIN RESULTS: Using reverse
      transcription-polymerase chain reaction and ELISA we showed that LPS-activated
      alveolar macrophages stimulated alveolar epithelial cells (AEC) to express growth
      factors, particularly GM-CSF, in coculture. Antibody neutralization experiments
      revealed epithelial GM-CSF expression to be macrophage tumor necrosis factor
      (TNF)-alpha dependent. GM-CSF elicited proliferative signaling in AEC via
      autocrine stimulation. Notably, macrophage TNF-alpha induced epithelial
      proliferation in wild-type but not in GM-CSF-deficient AEC as shown by [(3)H]
      thymidine incorporation and cell counting. Moreover, intraalveolar TNF-alpha
      neutralization impaired AEC proliferation in LPS-injured mice, as investigated by
      flow cytometric Ki-67 staining. Additionally, GM-CSF-deficient mice displayed
      reduced AEC proliferation and sustained alveolar barrier dysfunction on LPS
      treatment compared with wild-type mice. CONCLUSIONS: Collectively, these findings
      indicate that TNF-alpha released from activated resident alveolar macrophages
      induces epithelial GM-CSF expression, which in turn initiates AEC proliferation
      and contributes to restoring alveolar barrier function.

PMID- 19590024
TI  - Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model
      of tuberculosis.
AB  - RATIONALE: The diarylquinoline R207910 (TMC207) has potent bactericidal activity
      in a murine model of tuberculosis (TB), but its sterilizing activity has not been
      determined. OBJECTIVES: To evaluate the sterilizing activity of R207910
      containing combinations in the murine model of TB. METHODS: Swiss mice were
      intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain
      H37Rv, treated with R207910-containing regimens, and followed for 3 months to
      determine relapse rates (modified Cornell model). MEASUREMENTS AND MAIN RESULTS:
      Quantitative lung and spleen colony-forming unit counts and bacteriological
      relapse rates 3 months after the end of therapy were compared for the following
      regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with
      rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)
      containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated
      mice were culture negative after 4 months of therapy. The relapse rate in the
      group treated with 4 months of JHRZ was similar to that of mice treated for 6
      months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6
      vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in
      mice on once-daily basis. CONCLUSIONS: Four months of treatment with some J
      containing regimens was as effective as the 6-month standard regimen and more
      effective than 4 months of treatment with M-containing regimens. Supplementation
      of standard regimen (RHZ) with J or substitution of J for H may shorten the
      treatment duration needed to cure TB in patients.

PMID- 19590025
TI  - Physiotherapy at a distance: a controlled study of rehabilitation at home after a
      shoulder joint operation.
AB  - We explored the benefit of video communication in home rehabilitation after
      shoulder joint replacement and compared it to referral for physiotherapy in the
      conventional way. A total of 22 patients were included in the study. The
      intervention group (n = 10) had training at home under the supervision of a
      physiotherapist at the hospital using videoconferencing. The control group (n =
      12) had physiotherapy training in a conventional way in their home town. All
      patients had the same postoperative, three-phase-programme for two months. The
      outcome measures were a Visual Analogue Scale (VAS) for pain, range of motion
      (ROM), shoulder function ability (Constant score and SRQ-S) and health-related
      quality of life (SF-36). Questions about areas of priority for improvement and
      general satisfaction with the shoulder were also included. The telemedicine group
      received a greater number of treatments compared to the control group. After the
      intervention, there were significant improvements in VAS-pain, Constant score and
      SRQ-S for both groups. The telemedicine group improved significantly more in all
      three measurements than the control group (P < 0.001 for all). When changes from
      baseline to follow-up were compared, the telemedicine group improved
      significantly more in terms of decrease in pain (P = 0.004) and vitality (P =
      0.001) than the control group. Despite some limitations, there seem to be clear
      benefits from physiotherapy at a distance with a telemedicine technique that
      allows patients to obtain access to physiotherapy at home.

PMID- 19590026
TI  - A comparative study of teledermatoscopy and face-to-face examination of pigmented
      skin lesions.
AB  - We examined the agreement between diagnoses of pigmented skin lesions based on an
      in-person (face-to-face) dermatological examination and diagnoses based on the
      study of medical records and images transferred through the web
      (teledermatoscopy). Two experienced dermatologists examined and diagnosed 64
      pigmented skin lesions, which had been surgically excised and undergone
      histopathology examination. Two years later, the same cases were studied and
      diagnosed once again by the same dermatologists via the web. There was 72%
      agreement between the in-person diagnoses and the biopsy results (the gold
      standard), and 66% agreement between the telediagnoses and the biopsy results.
      Telemedicine had high sensitivity (87%) and specificity (73%), although there
      were 4 false-negative diagnoses. A web-based dermatoscopic diagnostic service
      appears to be feasible and would meet the needs for access to specialized
      services in rural areas. However, further work is required to decrease the number
      of false negative cases.

PMID- 19590027
TI  - Predicting need for intervention in individuals with congestive heart failure
      using a home-based telecare system.
AB  - We have studied how well the need for a medical intervention can be predicted by
      a telecare monitoring system. During a study period of about 18 months, 45
      elderly individuals with congestive heart failure used a home health monitor to
      enter daily information pertaining to their symptoms and health status. A total
      of 8576 alerts were generated by the monitoring system, although in most cases,
      patient and service provider interaction was not required. When system alerts
      were considered to be serious, or if symptoms persisted, the patient was
      contacted. A total of 171 key medical events (6 deaths; 28 hospital admissions;
      59 changes in medication; 54 cases of advice given; 24 instances where immediate
      medical attention was recommended) were recorded in the monitoring logs. A
      multivariate logistic regression model was developed to predict these medical
      interventions/events. The model correctly predicted key medical events in 75% of
      cases with a specificity of 74% and an overall cross-validated accuracy of 74%
      (95% CI, 68-80%). Key predictors included the number of system alerts, self-rated
      mobility, self-rated health and self-rated anxiety. This suggests that subjective
      measures are useful in addition to physiological ones for predicting health
      status. A multivariate decision support model has potential to supplement
      practitioners and current telecare systems in identifying heart failure patients
      in need of medical intervention.

PMID- 19590028
TI  - Assessment of communication and swallowing post-laryngectomy: a
      telerehabilitation trial.
AB  - Ten laryngectomy patients were assessed using a purpose-designed, multimedia
      videoconferencing system incorporating a freestanding, self-focusing camera.
      Swallowing, stoma and communication status were assessed simultaneously by a
      remote clinician and face-to-face, by a second clinician at the patient's site.
      The remote trial took place over a distance of approximately 1700 km using a
      commercial 3G phone network. A satisfaction questionnaire was also completed.
      There was excellent agreement between the two assessing clinicians. Image quality
      obtained via the freestanding camera was rated as lower than direct observation,
      but it was sufficient to assess the stoma and status of the voice prosthesis.
      During the trial, occasional difficulties with audio delays and image distortion
      were experienced, although these were manageable. Both patient and clinician
      satisfaction with remote assessment was high. The results provide further
      evidence to support the use of telerehabilitation for evaluating the speech and
      swallowing status of laryngectomy patients following discharge from acute care.

PMID- 19590029
TI  - The effect of telemedicine on outcome and quality of life in pregnant women with
      diabetes.
AB  - We evaluated the effect of a telemedicine system on maternal and fetal outcome in
      women with diabetes. A total of 276 pregnant women were enrolled in the study.
      Women were sequentially assigned to a telemedicine or a control group. There were
      88 women with gestational diabetes in the telemedicine group and 115 in the
      control group; there were 17 women with type 1 diabetes in the telemedicine group
      and 15 in the control group. Women in telemedicine groups were asked to submit
      their blood glucose data every week, and had a medical examination at the
      diabetes clinic once a month. Women in the control groups had a medical
      examination every two weeks. Subjective outcomes were investigated using the
      following questionnaires: CES-D for depression, SF-36 for health-related quality
      of life (QoL), Stress and Distress for the impact of diabetes. Clinical variables
      and pregnancy outcomes were no different between the two telemedicine groups,
      whereas women with gestational diabetes in the telemedicine group had a better
      metabolic control in the 3rd trimester and a lower rate of caesarean sections and
      macrosomia. As for QoL, women in the telemedicine groups showed lower levels of
      frustration and concerns about their diabetes, and a better acceptance of their
      diabetic condition. A questionnaire on the use of the telemedicine system showed
      a high degree of acceptance (85%). Both telemedicine groups had fewer check-ups
      at the diabetes clinics. The use of a telemedicine system for glucose monitoring
      improved pregnancy outcome in women with gestational diabetes and improved QoL in
      all diabetic pregnancies.

PMID- 19590030
TI  - Impact of electronic messaging on the patient-physician interaction.
AB  - Patients are interested in secure electronic communication with their health-care
      providers, but physicians have been slow to adopt the technique into their
      practice. We have therefore reviewed the literature on secure patient messaging.
      Relevant studies were identified by Medline search which produced 1065
      publications. Of these, 71 relevant articles were read independently by two
      reviewers. Currently available messaging systems allow for asynchronous
      communication, physician reimbursement and automated supporting functions such as
      triaging of patient messages and integration of messaging into medical records.
      The review showed that patients are satisfied with the use of secure physician
      messaging systems and find such services to be convenient, time-saving and
      useful. Physicians do not report adverse effects from their use. Legal concerns
      with electronic messaging include compliance with privacy standards. The economic
      benefits of secure messaging systems are most immediately apparent for larger
      health-care groups and hospitals, although smaller practices will also benefit in
      the long run. Secure patient-physician messaging is a convenient and useful
      addition to the health-care infrastructure. It can be expected that the
      identification of secure providers, integration with reimbursement systems and
      initial uptake by larger health-care organizations will speed up the adoption
      into routine health care.

PMID- 19590031
TI  - User's perceptions of remote trauma telesonography.
AB  - We established a pilot tele-ultrasound system between a rural referring hospital
      and a tertiary care trauma centre to facilitate telementoring during acute trauma
      resuscitations. Over a 12-month period, 23 tele-ultrasound examinations were
      completed. The clinical protocol examined both the Focused Assessment with
      Sonography for Trauma (FAST) and the Extended FAST (EFAST) for pneumothoraxes.
      Twenty of the examinations were conducted during acute trauma resuscitations and
      three during live patient simulations. FAST examinations were completed in all 23
      cases and EFAST examinations in 17 cases. There were 18 clinical users, of whom
      14 completed a survey (76% response rate). Overall, 93% of respondents were
      either satisfied or very satisfied with the telemedicine interaction and agreed
      or strongly agreed that the technology could potentially benefit injured patients
      in the far north of Canada. In addition, 93% of the respondents felt that the
      project had improved collegiality between the two institutions involved. The
      majority of respondents (71%) agreed or strongly agreed that the project had
      improved their ultrasound skills. We believe that as further experience is
      obtained, tele-ultrasound will prove to be an important aid to the care of
      remotely injured and ill patients.

PMID- 19590032
TI  - Need for tele follow-up--a study at a public sector quaternary referral hospital
      in India.
AB  - The All India Institute of Medical Sciences (AIIMS) is the apex super-specialty,
      quaternary referral hospital of India. Its outpatient departments (OPDs) handle
      over 2.5 million patients every year, a large proportion of whom travel up to
      2500 km for treatment because specialist facilities are not available in their
      regions. We conducted a descriptive study of 58 AIIMS faculty staff members,
      using a self-administered questionnaire followed by interviews with selected
      faculty members. During the year 2006, a total of 2,566,492 patients attended the
      various OPDs at the AIIMS, of whom 1,427,466 (56%) were old patients, i.e. they
      attended the OPD for follow-up. The questionnaire responses revealed that 55
      (95%) of the respondents routinely provided follow-up medical advice to their
      patients using the telephone, email and/or letters. Only 3 (5%) respondents
      stated that they did not use any such means for follow-up of their patients. Most
      of the respondents identified benefits in the use of telemedicine and did not
      envisage any major difficulties in using it for the follow-up of patients. If
      appropriate tele follow-up facilities were available, probably more than one
      million OPD visits could be avoided annually at the AIIMS.

PMID- 19590033
TI  - Impact of a telemedicine system on acute stroke care in a community hospital.
AB  - In January 2007, a telestroke system was established between a community hospital
      lacking a neurologist on call and a stroke centre 70 km away. The telestroke
      system allowed urgent remote evaluation of the patient by a specialized
      neurologist, supervised thrombolytic treatment or a decision for urgent transfer
      to the stroke centre. During the first year of operation of the telestroke
      system, we studied all acute ischaemic stroke patients admitted to the community
      hospital and compared the results with the previous year. Approximately the same
      number of acute stroke patients were admitted to the community hospital in each
      year (201 cases in 2006 and 198 in 2007). The telestroke system was activated 75
      times in 2007, the number of stroke patients evaluated by a specialized
      neurologist increased (17% vs. 38%, P > 0.001) and interhospital transfers were
      reduced (17% vs. 6%, P = 0.001). The number of thrombolytic treatments was
      doubled: 4.5% (n = 9) in 2006 vs. 9.6% (n = 19, 12 of them in the community
      hospital) in 2007 (P = 0.073). The telestroke system also reduced the time to tPA
      treatment from symptom onset (210 vs. 162 min, P = 0.05) and increased the number
      of patients treated in the 0-3 hours window (40% vs. 63%, P = 0.09). Telemedicine
      improved the quality of care administered to acute stroke patients admitted to a
      community hospital and reduced the number of inter-hospital transfers.

PMID- 19590034
TI  - Complex bioethics consultation in rural hospitals: using telemedicine to bring
      academic bioethicists into outlying communities.
AB  - Bioethics consultations are necessary to ensure excellent patient care and all US
      hospitals are required to provide access to bioethics consultants for cases
      raising ethical or moral dilemmas. However, there is a paucity of trained
      clinical ethicists. While assistance from trained bioethicists may be obtained
      via telephone or email, such methods of contact do not allow a bioethicist to
      engage fully with all members of the health-care team, the patient and family
      members. In two recent cases, rural hospitals contacted our centre for assistance
      with complex ethics cases. We provided a clinical ethics consultation via
      videoconferencing. The outcomes of the consultations would probably have been
      inferior had they been performed via telephone. For example, the non-verbal cues
      allowed the consultants to have a better understanding of the team dynamics, and
      led them to ask important questions that directly affected the recommendations
      which were made. Because patients are likely to benefit significantly from access
      to bioethicists when ethical questions arise, rural and community hospitals
      should consider teleconsultation when local ethics committees decide that further
      assistance is warranted.

PMID- 19590036
TI  - MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in
      mouse skin wound healing.
AB  - Matrix metalloproteinases (MMPs) have been implicated in wound healing. To
      analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full
      thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO,
      and wild-type mice. Macroscopic wound closure was delayed in all of the KO mice,
      as compared with wild-type mice. The rate of re-epithelialization was
      significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in
      MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13
      were expressed by the leading edges of epidermal cells in wild-type mice, and the
      migration of keratinocytes was suppressed by treatment with an MMP inhibitor or
      transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with
      controls. The vascular density in wound granulation was significantly lower in
      both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of
      connective tissue growth factor in wound tissue was transiently prevented in MMP
      13 KO mice. Morphometric analyses demonstrated a reduction in both wound
      contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO
      mice. Proliferation and transforming growth factor-beta1-induced myofibroblast
      differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as
      compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays
      a role in keratinocyte migration, angiogenesis, and contraction in wound healing,
      while MMP-9 functions in keratinocyte migration.

PMID- 19590037
TI  - Peroxidasin is secreted and incorporated into the extracellular matrix of
      myofibroblasts and fibrotic kidney.
AB  - Mammalian peroxidases are heme-containing enzymes that serve diverse biological
      roles, such as host defense and hormone biosynthesis. A mammalian homolog of
      Drosophila peroxidasin belongs to the peroxidase family; however, its function is
      currently unknown. In this study, we show that peroxidasin is present in the
      endoplasmic reticulum of human primary pulmonary and dermal fibroblasts, and the
      expression of this protein is increased during transforming growth factor-beta1
      induced myofibroblast differentiation. Myofibroblasts secrete peroxidasin into
      the extracellular space where it becomes organized into a fibril-like network and
      colocalizes with fibronectin, thus helping to form the extracellular matrix. We
      also demonstrate that peroxidasin expression is increased in a murine model of
      kidney fibrosis and that peroxidasin localizes to the peritubular space in
      fibrotic kidneys. In addition, we show that this novel pathway of extracellular
      matrix formation is unlikely mediated by the peroxidase activity of the protein.
      Our data indicate that peroxidasin secretion represents a previously unknown
      pathway in extracellular matrix formation with a potentially important role in
      the physiological and pathological fibrogenic response.

PMID- 19590038
TI  - Arginase activity mediates retinal inflammation in endotoxin-induced uveitis.
AB  - Arginase has been reported to reduce nitric oxide bioavailability in
      cardiovascular disease. However, its specific role in retinopathy has not been
      studied. In this study, we assessed the role of arginase in a mouse model of
      endotoxin-induced uveitis induced by lipopolysaccharide (LPS) treatment.
      Measurement of arginase expression and activity in the retina revealed a
      significant increase in arginase activity that was associated with increases in
      both mRNA and protein levels of arginase (Arg)1 but not Arg2. Immunofluorescence
      and flow cytometry confirmed this increase in Arg1, which was localized to glia
      and microglia. Arg1 expression and activity were also increased in cultured
      Muller cells and microglia treated with LPS. To test whether arginase has a role
      in the development of retinal inflammation, experiments were performed in mice
      deficient in one copy of the Arg1 gene and both copies of the Arg2 gene or in
      mice treated with a selective arginase inhibitor. These studies showed that LPS
      induced increases in inflammatory protein production, leukostasis, retinal
      damage, signs of anterior uveitis, and uncoupling of nitric oxide synthase were
      blocked by either knockdown or inhibition of arginase. Furthermore, the LPS
      induced increase in Arg1 expression was abrogated by blocking NADPH oxidase. In
      conclusion, these studies suggest that LPS-induced retinal inflammation in
      endotoxin-induced uveitis is mediated by NADPH oxidase-dependent increases in
      arginase activity.

PMID- 19590039
TI  - Expression of RNA CCUG repeats dysregulates translation and degradation of
      proteins in myotonic dystrophy 2 patients.
AB  - Myotonic dystrophy 2 (DM2) is a multisystem skeletal muscle disease caused by an
      expansion of tetranucleotide CCTG repeats, the transcription of which results in
      the accumulation of untranslated CCUG RNA. In this study, we report that CCUG
      repeats both bind to and misregulate the biological functions of cytoplasmic
      multiprotein complexes. Two CCUG-interacting complexes were subsequently purified
      and analyzed. A major component of one of the complexes was found to be the 20S
      catalytic core complex of the proteasome. The second complex was found to contain
      CUG triplet repeat RNA-binding protein 1 (CUGBP1) and the translation initiation
      factor eIF2. Consistent with the biological functions of the 20S proteasome and
      the CUGBP1-eIF2 complexes, the stability of short-lived proteins and the levels
      of the translational targets of CUGBP1 were shown to be elevated in DM2
      myoblasts. We found that the overexpression of CCUG repeats in human myoblasts
      from unaffected patients, in C2C12 myoblasts, and in a DM2 mouse model alters
      protein translation and degradation, similar to the alterations observed in DM2
      patients. Taken together, these findings show that RNA CCUG repeats misregulate
      protein turnover on both the levels of translation and proteasome-mediated
      protein degradation.

PMID- 19590040
TI  - Inhibition of receptor activator of NF-kappaB ligand by denosumab attenuates
      vascular calcium deposition in mice.
AB  - Osteoporosis and vascular calcification frequently coincide. A potential mediator
      of bone metabolism and vascular homeostasis is the triad cytokine system, which
      consists of receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL),
      its receptor RANK, and the decoy receptor osteoprotegerin. Unopposed RANKL
      activity in osteoprotegerin-deficient mice resulted in osteoporosis and vascular
      calcification. We therefore analyzed the effects of RANKL inhibition by
      denosumab, a human monoclonal antibody against RANKL, on vascular calcium
      deposition following glucocorticoid exposure. Prednisolone pellets were implanted
      into human RANKL knock-in (huRANKL-KI) mice, which unlike wild-type mice are
      responsive to denosumab. No histomorphological abnormalities or differences in
      aortic wall thickness were detected between wild-type and huRANKL-KI mice,
      regardless of treatment with prednisolone, denosumab, or both. However,
      concurrent treatment with denosumab reduced aortic calcium deposition of
      prednisolone-treated huRANKL-KI mice by up to 50%, based on calcium measurement.
      Of note, aortic calcium deposition in huRANKL-KI mice was correlated negatively
      with bone mineral density at the lumbar spine (P = 0.04) and positively with
      urinary excretion of deoxypyridinoline, a marker of bone resorption (P = 0.01).
      In summary, RANKL inhibition by denosumab reduced vascular calcium deposition in
      glucocorticoid-induced osteoporosis in mice, which is further evidence for the
      link between the bone and vascular systems. Therefore, the prevention of bone
      loss by denosumab might also be associated with reduced vascular calcification in
      certain conditions.

PMID- 19590041
TI  - Disruption of E-cadherin by matrix metalloproteinase directly mediates epithelial
      mesenchymal transition downstream of transforming growth factor-beta1 in renal
      tubular epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) plays an important role in organ
      fibrosis, including that of the kidney. Loss of E-cadherin expression is a
      hallmark of EMT; however, whether the loss of E-cadherin is a consequence or a
      cause of EMT remains unknown, especially in the renal system. In this study, we
      show that transforming growth factor (TGF)-beta1-induced EMT in renal tubular
      epithelial cells is dependent on proteolysis. Matrix metalloproteinase-mediated E
      cadherin disruption led directly to tubular epithelial cell EMT via Slug. TGF
      beta1 induced the proteolytic shedding of E-cadherin, which caused the nuclear
      translocation of beta-catenin, the transcriptional induction of Slug, and the
      repression of E-cadherin transcription in tubular epithelial cells. These
      findings reveal a direct role for E-cadherin and for matrix metalloproteinases in
      causing EMT downstream of TGF-beta1 in fibrotic disease. Specific inhibition
      rather than activation of matrix metalloproteinases may offer a novel approach
      for treatment of fibrotic disease.

PMID- 19590042
TI  - Differential interferon responses enhance viral epitope generation by myocardial
      immunoproteasomes in murine enterovirus myocarditis.
AB  - Murine models of coxsackievirus B3 (CVB3)-induced myocarditis mimic the divergent
      human disease course of cardiotropic viral infection, with host-specific outcomes
      ranging from complete recovery in resistant mice to chronic disease in
      susceptible hosts. To identify susceptibility factors that modulate the course of
      viral myocarditis, we show that type-I interferon (IFN) responses are
      considerably impaired in acute CVB3-induced myocarditis in susceptible mice,
      which have been linked to immunoproteasome (IP) formation. Here we report that in
      concurrence with distinctive type-I IFN kinetics, myocardial IP formation peaked
      early after infection in resistant mice and was postponed with maximum IP
      expression concomitant to massive inflammation and predominant type-II IFN
      responses in susceptible mice. IP activity is linked to a strong enhancement of
      antigenic viral peptide presentation. To investigate the impact of myocardial IPs
      in CVB3-induced myocarditis, we identified two novel CVB3 T cell epitopes, virus
      capsid protein 2 [285-293] and polymerase 3D [2170-2177]. Analysis of myocardial
      IPs in CVB3-induced myocarditis revealed that myocardial IP expression resulted
      in efficient epitope generation. As opposed to the susceptible host, myocardial
      IP expression at early stages of disease corresponded to enhanced CVB3 epitope
      generation in the hearts of resistant mice. We propose that this process may
      precondition the infected heart for adaptive immune responses. In conclusion,
      type-I IFN-induced myocardial IP activity at early stages coincides with less
      severe disease manifestation in CVB3-induced myocarditis.

PMID- 19590043
TI  - ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac
      dorsal root ganglia neurons.
AB  - RATIONALE: Acid-sensing ion channels (ASICs) are Na+ channels that are activated
      by acidic pH. Their expression in cardiac afferents and remarkable sensitivity to
      small pH changes has made them leading candidates to sense cardiac ischemia.
      OBJECTIVE: Four genes encode six different ASIC subunits, however it is not yet
      clear which of the ASIC subunits contribute to the composition of ASICs in
      cardiac afferents. METHODS AND RESULTS: Here, we labeled cardiac afferents using
      a retrograde tracer dye in mice, which allowed for patch-clamp studies of murine
      cardiac afferents. We found that a higher percentage of cardiac sensory neurons
      from the dorsal root ganglia respond to acidic pH and generated larger currents
      compared to those from the nodose ganglia. The ASIC-like current properties of
      the cardiac dorsal root ganglia neurons from wild-type mice most closely matched
      the properties of ASIC2a/3 heteromeric channels. This was supported by studies in
      ASIC-null mice: acid-evoked currents from ASIC3(-/-) cardiac afferents matched
      the properties of ASIC2a channels, and currents from ASIC2(-/-) cardiac afferents
      matched the properties of ASIC3 channels. CONCLUSIONS: We conclude that ASIC2a
      and -3 are the major ASIC subunits in cardiac dorsal root ganglia neurons and
      provide potential molecular targets to attenuate chest pain and deleterious
      reflexes associated with cardiac disease.

PMID- 19590044
TI  - Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiac
      myosin-binding protein C mutant levels in cardiomyopathic mice.
AB  - RATIONALE: Mutations in the MYBPC3 gene encoding cardiac myosin-binding protein
      (cMyBP)-C are frequent causes of hypertrophic cardiomyopathy, but the mechanisms
      leading from mutations to disease remain elusive. OBJECTIVE: The goal of the
      present study was therefore to gain insights into the mechanisms controlling the
      expression of MYBPC3 mutations. METHODS AND RESULTS: We developed a cMyBP-C knock
      in mouse carrying a point mutation. The level of total cMyBP-C mRNAs was 50% and
      80% lower in heterozygotes and homozygotes, respectively. Surprisingly, the
      single G>A transition on the last nucleotide of exon 6 resulted in 3 different
      mutant mRNAs: missense (exchange of G for A), nonsense (exon skipping,
      frameshift, and premature stop codon) and deletion/insertion (as nonsense but
      with additional partial retention of downstream intron, restoring of the reading
      frame, and almost full-length protein). Inhibition of nonsense-mediated mRNA
      decay in cultured cardiac myocytes or in vivo with emetine or cycloheximide
      increased the level of nonsense mRNAs severalfold but not of the other mRNAs. By
      using sequential protein fractionation and a new antibody directed against novel
      amino acids produced by the frameshift, we showed that inhibition of the
      proteasome with epoxomicin via osmotic minipumps increased the level of (near)
      full-length mutants but not of truncated proteins. Homozygotes exhibited myocyte
      and left ventricular hypertrophy, reduced fractional shortening, and interstitial
      fibrosis; heterozygotes had no major phenotype. CONCLUSIONS: These data reveal
      (1) an unanticipated complexity of the expression of a single point mutation in
      the whole animal and (2) the involvement of both nonsense-mediated mRNA decay and
      the ubiquitin-proteasome system in lowering the level of mutant proteins.

PMID- 19590045
TI  - Identification and functional characterization of cardiac troponin I as a novel
      disease gene in autosomal dominant dilated cardiomyopathy.
AB  - RATIONALE: Idiopathic dilated cardiomyopathy (DCM) is inherited in approximately
      one third of cases, usually as an autosomal dominant trait. More than 30 loci
      have been identified, several of which encode sarcomeric proteins which can also
      be mutated to cause hypertrophic cardiomyopathy. One contractile protein gene
      well known as a hypertrophic cardiomyopathy disease gene, but with no reported
      mutation in autosomal dominant DCM, is TNNI3 which encodes cardiac troponin I.
      OBJECTIVE: To test TNNI3 as a candidate gene, a panel of 96 probands with DCM was
      analyzed. METHODS AND RESULTS: Genomic DNA was isolated and TNNI3 exons screened
      by heteroduplex analysis. Exons with aberrant profiles were sequenced and
      variants evaluated by segregation analysis and study of normal controls. We
      report 2 novel TNNI3 missense mutations, Lys36Gln and Asn185Lys, each associated
      with severe and early onset familial DCM. Of the 5 mutation carriers, cardiac
      transplantation was required in 3, at ages 6, 15, and 24 years. Analysis of
      Ca(2+) regulation of actin-tropomyosin-activated myosin ATPase by troponin
      revealed that troponin reconstituted with either mutant troponin I gave lower
      maximum ATPase rates and lower Ca(2+) sensitivity than wild type. Furthermore,
      mutant thin filaments had reduced Ca(2+) affinity compared with normal.
      CONCLUSIONS: The functional alterations mirror closely a consistent phenotype
      found in proven DCM mutations in other thin filament proteins, thus supporting
      the interpretation that these mutations are disease-causing. These are the first
      reported autosomal dominant DCM-causing mutations in TNNI3, and so the findings
      expand the spectrum of disease-causing genes that lead to either hypertrophic
      cardiomyopathy or DCM depending on the specific mutation.

PMID- 19590046
TI  - Angiomotin-like protein 1 controls endothelial polarity and junction stability
      during sprouting angiogenesis.
AB  - RATIONALE: We have previously shown that angiomotin (Amot) is essential for
      endothelial cell migration during mouse embryogenesis. However, approximately 5%
      of Amot knockout mice survived without any detectable vascular defects.
      Angiomotin-like protein 1 (AmotL1) potentially compensates for the absence of
      Amot as it is 62% homologous to Amot and exhibits similar expression pattern in
      endothelial cells. OBJECTIVE: Here, we report the identification of a novel
      isoform of AmotL1 that controls endothelial cell polarization and directional
      migration. METHODS AND RESULTS: Small interfering RNA-mediated silencing of
      AmotL1 in mouse aortic endothelial cells caused a significant reduction in
      migration. In confluent mouse pancreatic islet endothelial cells (MS-1), AmotL1
      colocalized with Amot to tight junctions. Small interfering RNA knockdown of both
      Amot and AmotL1 in MS-1 cells exhibited an additive effect on increasing
      paracellular permeability compared to that of knocking down either Amot or
      AmotL1, indicating both proteins were required for proper tight junction
      activity. Moreover, as visualized using high-resolution 2-photon microscopy, the
      morpholino-mediated knockdown of amotl1 during zebrafish embryogenesis resulted
      in vascular migratory defect of intersegmental vessels with strikingly decreased
      junction stability between the stalk cells and the aorta. However, the phenotype
      was quite distinct from that of amot knockdown which affected polarization of the
      tip cells of intersegmental vessels. Double knockdown resulted in an additive
      phenotype of depolarized tip cells with no or decreased connection of the stalk
      cells to the dorsal aorta. CONCLUSIONS: These results cumulatively validate that
      Amot and AmotL1 have similar effects on endothelial migration and tight junction
      formation in vitro. However, in vivo Amot appears to control the polarity of
      vascular tip cells whereas AmotL1 mainly affects the stability of cell-cell
      junctions of the stalk cells.

PMID- 19590048
TI  - When recanalization does not improve clinical outcomes.

PMID- 19590047
TI  - Macrophage sphingomyelin synthase 2 deficiency decreases atherosclerosis in mice.
AB  - RATIONALE: Sphingomyelin synthase (SMS)2 contributes to de novo sphingomyelin
      (SM) biosynthesis and plasma membrane SM levels. SMS2 deficiency in macrophages
      diminishes nuclear factor kappaB and mitogen-activated protein kinase activation
      induced by inflammatory stimuli. OBJECTIVE: The effects of SMS2 deficiency on the
      development of atherosclerosis are investigated. METHODS AND RESULTS: We measured
      cholesterol efflux from macrophages of wild-type (WT) and SMS2 knockout (KO)
      mice. We transplanted SMS2 KO mouse bone marrow into low-density lipoprotein
      (LDL) receptor (LDLr) knockout mice (SMS2(-/-)-->LDLr(-/-)), creating a mouse
      model of SMS2 deficiency in the macrophages. We found that SMS2 deficiency caused
      significant induction of cholesterol efflux in vitro and in vivo. Moreover, we
      found that SMS2 KO mice had less interleukin-6 and tumor necrosis factor alpha in
      the circulation before and after endotoxin stimulation, compared with controls.
      More importantly, after 3 months on a western-type diet, SMS2(-/-)-->LDLr(-/-)
      mice showed decreased atherosclerotic lesions in the aortic arch, root (57%,
      P<0.001), and the entire aorta (42%, P<0.01), compared with WT-->LDLr(-/-) mice.
      Analysis of plaque morphology revealed that SMS2(-/-)-->LDLr(-/-) mice had
      significantly less necrotic core area (71%, P<0.001), less macrophage content
      (37%, P<0.01), and more collagen content (35%, P<0.05) in atherosclerotic
      lesions. We also found that SMS2(-/-)-->LDLr(-/-) mice had significantly lower
      free cholesterol and cholesteryl ester levels in the brachiocephalic artery than
      WT-->LDLr(-/-) mice (33 and 52%, P<0.01 and P<0.001, respectively). CONCLUSIONS:
      SMS2 deficiency in the macrophages reduces atherosclerosis in mice. Macrophage
      SMS2 is thus a potential therapeutic target for treatment of this disease.

PMID- 19590049
TI  - Statins and gender-related difference in endothelial function in cerebral small
      vessel disease.

PMID- 19590050
TI  - Neuropsychological assessment: sense and sensibility.

PMID- 19590051
TI  - Brain temperature measured using proton MR spectroscopy detects cerebral
      hemodynamic impairment in patients with unilateral chronic major cerebral artery
      steno-occlusive disease: comparison with positron emission tomography.
AB  - BACKGROUND AND PURPOSE: Brain temperature is determined by the balance between
      heat produced by cerebral energy turnover and heat removed by cerebral blood
      flow. The purpose of the present study was to investigate whether brain
      temperature measured noninvasively using proton MR spectroscopy can detect
      cerebral hemodynamic impairment in patients with unilateral chronic internal
      carotid or middle cerebral artery occlusive disease when compared with positron
      emission tomography. METHODS: Brain temperature, cerebral blood flow, and
      metabolism were measured using proton MR spectroscopy and (15)O-positron emission
      tomography, respectively, in 21 normal subjects and 37 patients. Positron
      emission tomography images were coregistered with MR images and resliced
      automatically using image analysis software. Regions of interest placed in both
      cerebral hemispheres on MR images were automatically superimposed in these
      resliced positron emission tomography images. RESULTS: A significant correlation
      was observed between brain temperature difference (affected hemisphere
      contralateral hemisphere) and both cerebral blood volume and oxygen extraction
      fraction ratio (affected hemisphere/contralateral hemisphere; r=0.607; P=0.0004
      and r=0.631; P=0.0002). With abnormally elevated cerebral blood volume or oxygen
      extraction fraction ratio defined as higher than the mean +2 SDs obtained from
      normal subjects, brain temperature difference provided 86% or 92% sensitivity and
      87% or 84% specificity with 80% or 73% positive and 91% or 95% negative
      predictive values for detecting abnormally elevated cerebral blood volume or
      oxygen extraction fraction ratios, respectively. CONCLUSIONS: Brain temperature
      measured using proton MR spectroscopy can detect cerebral hemodynamic impairment
      in patients with unilateral chronic major cerebral artery steno-occlusive
      disease.

PMID- 19590052
TI  - Causes of death and predictors of 5-year mortality in young adults after first
      ever ischemic stroke: the Helsinki Young Stroke Registry.
AB  - BACKGROUND AND PURPOSE: Data on mortality and its prognostic factors after an
      acute ischemic stroke in young adults are scarce and based on relatively small
      heterogeneous patient series. METHODS: We analyzed 5-year mortality data of all
      consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the
      Department of Neurology, Helsinki University Central Hospital, from January 1994
      to September 2003. We followed up the patients using data from the mortality
      registry of Statistics Finland. We used life table analyses for calculating
      mortality risks. Kaplan-Meier method allowed comparisons of survival between
      clinical subgroups. We used the Cox proportional hazard model for identifying
      predictors of mortality. Stroke severity was measured using the National
      Institutes of Health Stroke Scale and the Glasgow Coma Scale. RESULTS: Among the
      731 patients (mean age, 41.5+/-7.4 years; 62.8% males) followed, 78 died.
      Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7%
      (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender
      difference. Those > or =45 years of age had lower probabilities of survival.
      Among the 30-day survivors (n=711), stroke caused 21%, cardioaortic and other
      vascular causes 36%, malignancies 12%, and infections 9% of the deaths.
      Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes,
      increasing age, and large artery atherosclerosis causing the index stroke
      independently predicted 5-year mortality adjusted for age, gender, relevant risk
      factors, stroke severity, and etiologic subtype. CONCLUSIONS: Despite the overall
      low mortality after an ischemic stroke in young adults, several recognizable
      subgroups had substantially increased risk of death in the long term.

PMID- 19590053
TI  - Placebo-controlled trial of high-dose atorvastatin in patients with severe
      cerebral small vessel disease.

PMID- 19590054
TI  - P-selectin 1087G/A polymorphism is associated with neuropsychological test
      performance in older adults with cardiovascular disease.
AB  - BACKGROUND AND PURPOSE: There is growing evidence that the cell adhesion molecule
      P-selectin (SELP) contributes to the adverse vascular processes that promote
      cognitive impairment in individuals with cardiovascular disease. Previous
      research has shown that SELP genotypes moderate circulating levels of P-selectin
      and that patients undergoing coronary artery bypass graft with the SELP 1087A
      allele were less likely to show postoperative cognitive decline and more likely
      to exhibit lower levels of C-reactive protein than noncarriers. Thus, we expected
      that carriers of the 1087A allele (n=43) would exhibit better cognitive
      functioning than persons with 2 1087G alleles (n=77) and that C-reactive protein
      levels would be important for this relationship. METHODS: One hundred twenty
      older adults with diagnosed cardiovascular disease were recruited from outpatient
      cardiology clinics. Each participant underwent a comprehensive neuropsychological
      test battery and a blood draw. RESULTS: Participants with the SELP 1087A allele
      performed more poorly on tests of attention (Trail Making Test A: t[116]=3.20,
      P=0.002), executive function (Trail Making Test B: t[116]=2.89, P=0.005),
      psychomotor speed (Digit-Symbol Coding: t[117]=2.54, P=0.012), and memory
      (California Verbal Learning Test Discrimination: t[116]=2.05, P=0.04). There were
      no significant differences between the SELP genotype groups on
      demographic/medical variables or C-reactive protein levels. CONCLUSIONS: Contrary
      to expectations, the present analyses showed that older patients with
      cardiovascular disease with the SELP 1087A allele performed more poorly on
      neuropsychological testing. Findings from the present study were counter to
      previous research with coronary artery bypass graft candidates. Further work
      using neuroimaging and alternative measures of cardiovascular function is needed
      to clarify the mechanisms of this association.

PMID- 19590055
TI  - Collateral vessels on CT angiography predict outcome in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Despite the abundance of emerging multimodal imaging
      techniques in the field of stroke, there is a paucity of data demonstrating a
      strong correlation between imaging findings and clinical outcome. This study
      explored how proximal arterial occlusions alter flow in collateral vessels and
      whether occlusion or extent of collaterals correlates with prehospital symptoms
      of fluctuation and worsening since onset or predict in-hospital worsening.
      METHODS: Among 741 patients enrolled in a prospective cohort study involving CT
      angiographic imaging in acute stroke, 134 cases with proximal middle cerebral
      artery occlusion and 235 control subjects with no occlusions were identified. CT
      angiography was used to identify occlusions and grade the extent of collateral
      vessels in the sylvian fissure and leptomeningeal convexity. History of symptom
      fluctuation or progressive worsening was obtained on admission. RESULTS:
      Prehospital symptoms were unrelated to occlusion or collateral status. In cases,
      37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1%
      imaged at 12 to 24 hours (P=0.047). No difference in worsening was seen between
      cases and control subjects with adequate collaterals, but cases with diminished
      sylvian and leptomeningeal collaterals experienced greater risk of worsening
      compared with control subjects measured either by admission to discharge National
      Institutes of Health Stroke Scale increase > or =1 (55.6% versus 16.6%, P=0.001)
      or > or =4 (44.4% versus 6.4%, P<0.001). CONCLUSIONS: Most patients with proximal
      middle cerebral artery occlusion rapidly recruit sufficient collaterals and
      follow a clinical course similar to patients with no occlusions, but a subset
      with diminished collaterals is at high risk for worsening.

PMID- 19590056
TI  - The cost of pediatric stroke acute care in the United States.
AB  - BACKGROUND AND PURPOSE: The cost of pediatric stroke care has received little
      attention, but the available data suggest it is expensive. To determine the cost
      of acute stroke, we analyzed a US national database. Method- We used the Kids'
      Inpatient Database (KID2003) to determine the hospital-based costs of acute
      stroke in children ages 3 months to 20 years. Discharges were selected if the
      first diagnostic position contained an International Classification of Diseases,
      9th Revision code pertaining to ischemic or hemorrhagic stroke. We examined the
      relationship between cost and stroke type by adjusting for variables that predict
      the cost of adult stroke. RESULTS: There were 2224 pediatric cases, after
      statistical weighting, discharged with a diagnosis of hemorrhagic or ischemic
      stroke in KID2003. The estimated cost of acute pediatric stroke in the United
      States was $42 million in 2003. For the entire cohort, the mean cost of acute
      hospital care was $20 927 per discharge. The mean cost for ischemic stroke was
      $15 003, for intracerebral hemorrhage $24 117, and for subarachnoid hemorrhage
      $31 653. Stroke diagnosis, length of stay, hospital ownership, rural/urban
      teaching status, US geographical region, and discharge disposition were
      significantly associated with cost. Cost remained significantly associated with
      stroke diagnosis after adjusting for other predictors in the final multivariable
      regression model. CONCLUSIONS: Pediatric stroke is expensive, and the lifetime
      cost of care is likely greater for a child than an adult. The cost to the family
      and the larger society underscore the importance of pediatric stroke treatment
      and prevention.

PMID- 19590057
TI  - The penumbra pivotal stroke trial: safety and effectiveness of a new generation
      of mechanical devices for clot removal in intracranial large vessel occlusive
      disease.
AB  - BACKGROUND AND PURPOSE: The purpose of this clinical evaluation was to assess the
      safety and effectiveness of the Penumbra System in the revascularization of
      patients presenting with acute ischemic stroke secondary to intracranial large
      vessel occlusive disease. METHODS: In this prospective, multicenter, single-arm
      study, 125 patients with neurological deficits as defined by a National
      Institutes of Health Stroke Scale score > or =8, presented within 8 hours of
      symptom onset, and an angiographic occlusion (Thrombolysis In Myocardial
      Infarction [TIMI] Grade 0 or 1) of a treatable large intracranial vessel were
      enrolled. Patients who presented within 3 hours from symptom onset had to be
      ineligible or refractory to recombinant tissue plasminogen activator therapy. All
      patients were followed clinically for 90 days postprocedure. RESULTS: A total of
      125 target vessels in 125 patients were treated by the Penumbra System.
      Postprocedure, 81.6% of the treated vessels were successfully revascularized to
      TIMI 2 to 3. There were 18 procedural events reported in 16 patients (12.8%), 3
      patients (2.4%) had events that were considered serious. A total of 35 patients
      (28%) were found to have intracranial hemorrhage on 24-hour CT of which 14
      (11.2%) were symptomatic. All cause mortality was 32.8% at 90 days with 25% of
      the patients achieving a modified Rankin Scale score of < or =2. CONCLUSIONS:
      These results suggest the Penumbra System allows safe and effective
      revascularization in patients experiencing ischemic stroke secondary to large
      vessel occlusive disease who present within 8 hours from symptom onset.

PMID- 19590059
TI  - A novel role for nephrin in the maintenance of glomerular structure.

PMID- 19590058
TI  - Second primary breast cancer occurrence according to hormone receptor status.
AB  - BACKGROUND: Contralateral second primary breast cancers occur in 4% of female
      breast cancer survivors. Little is known about differences in risk for second
      primary breast cancers related to the estrogen and progesterone receptor (hormone
      receptor [HR]) status of the first tumor. METHODS: We calculated standardized
      incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral
      primary breast cancers among 4927 women diagnosed with a first breast cancer
      between January 1, 1992, and December 31, 2004, using the National Cancer
      Institute's Surveillance, Epidemiology, and End Results database. RESULTS: For
      women whose first breast tumors were HR positive, risk of contralateral primary
      breast cancer was elevated, compared with the general population, adjusted for
      age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk
      [AR] = 13 cases per 10 000 person-years [PY]), and was not related to the HR
      status of the second tumor. For women whose first breast tumors were HR negative,
      the risk of a contralateral primary tumor was statistically significantly higher
      than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI =
      3.38 to 3.78, AR = 18 per 10 000 PY), and it was associated with a much greater
      likelihood of an HR-negative second tumor (SIR for HR-positive second tumors =
      1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10 000 PY; SIR for HR-negative second
      tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10 000 PY). Women who were
      initially diagnosed with HR-negative tumors when younger than 30 years had
      greatly elevated risk of HR-negative contralateral tumors, compared with the
      general population (SIR = 169, 95% CI = 106 to 256, AR = 77 per 10 000 PY).
      Incidence rates for any contralateral primary cancer following an HR-negative or
      HR-positive tumor were higher in non-Hispanic blacks, Hispanics, and Asians or
      Pacific Islanders than in non-Hispanic whites. CONCLUSIONS: Risk for
      contralateral second primary breast cancers varies substantially by HR status of
      the first tumor, age, and race and/or ethnicity. Women with HR-negative first
      tumors have nearly a 10-fold elevated risk of developing HR-negative second
      tumors, compared with the general population. These findings warrant intensive
      surveillance for second breast cancers in women with HR-negative tumors.

PMID- 19590060
TI  - A large family with a gain-of-function mutation of complement C3 predisposing to
      atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic
      renal failure.
AB  - BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome (aHUS) is
      associated with mutations in genes encoding complement-regulatory proteins factor
      H, I and B and membrane cofactor protein. Recently, heterozygous gain-of-function
      mutations in the complement C3 gene have been found in patients with aHUS.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A large family with a C3 R570Q
      mutation is described. Clinical and laboratory findings of carriers of the
      mutation and unaffected family members are reported. RESULTS: The index patient
      suffered from recurrent aHUS at age 22 and developed end-stage renal failure. Of
      24 family members, nine harbored the C3 R570Q mutation. Carriers showed reduced
      or borderline C3 levels. Arterial hypertension was found in six family members,
      microhematuria in five and chronic kidney disease stage 3 in two elderly carrier
      patients. Despite marked consumption of C3, serum terminal complement complex
      levels were not elevated in carriers compared with other family members.
      CONCLUSIONS: The penetrance of the C3 R570Q mutation to induce aHUS is incomplete
      and lower compared with mutations in other genes predisposing to the disease. The
      mutation is possibly also associated with hypertension, hematuria and chronic
      kidney disease, all of which may represent consequences of long-term complement
      activation in the renal vasculature.

PMID- 19590061
TI  - Does timing of dialysis in patients with ESRD and acute myocardial infarcts
      affect morbidity or mortality?
AB  - BACKGROUND AND OBJECTIVES: Patients with ESRD have an increased incidence of
      coronary events with a relatively higher risk for mortality after acute
      myocardial infarction (AMI). We evaluated whether it is safer to delay dialysis
      in AMI or if delay poses separate risks. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We conducted a retrospective review of 131 long-term hemodialysis
      patients who had AMI and were admitted between 1997 and 2005 at three New York
      City municipal hospitals. Patients were separated into three groups on the basis
      of time between cardiac symptoms and first dialysis (<24 h, 24 to 48 h, and >48
      h). RESULTS: A total of 17 (13%) patients died, 10 (59%) of whom had either
      hypotension or an arrhythmia during their first cardiac care unit dialysis.
      Although these groups were comparable in acuity and cardiac status, there were no
      findings of increased morbidity (26, 36, and 20%, respectively) or mortality (11,
      18, and 13%, respectively), despite differences in the timing of each group's
      dialysis. We found that previous cardiac disease, predialysis K+, DeltaK+ after
      dialysis, and APACHE scores were significantly higher in patients with
      peridialysis morbidity. CONCLUSIONS: We conclude that there is no increased
      morbidity with early dialysis in AMI, but rather close attention needs to be paid
      to the rate of decrease in serum potassium in patients with ESRD and their level
      of acuity when undergoing dialysis.

PMID- 19590063
TI  - Staphylococcus aureus infections in hemodialysis: what a nephrologist should
      know.
AB  - Staphylococcus aureus is a formidable pathogen that has the ability to colonize
      approximately half the dialysis population without any sign of disease but is
      also capable of causing wound and tissue infections; fulminant septicemia; and
      chronic, difficult-to-eradicate and often foreign body-related infections. S.
      aureus is the main cause of infectious morbidity and mortality in hemodialysis
      patients. This review highlights the importance of S. aureus infections in daily
      hemodialysis practice from a clinical viewpoint, starting from some key issues in
      the pathogenesis of staphylococcal infections.

PMID- 19590064
TI  - Editorial: metrics and accountability--expectations, evaluations, and thinking
      big.

PMID- 19590065
TI  - Evaluation of sample preservation methods for poultry manure.
AB  - When poultry manure is collected but cannot be analyzed immediately, a method for
      storing the manure is needed to ensure accurate subsequent analyses. This study
      has 3 objectives: (1) to investigate effects of 4 poultry manure sample
      preservation methods (refrigeration, freezing, acidification, and freeze-drying)
      on the compositional characteristics of poultry manure; (2) to determine
      compositional differences in fresh manure with manure samples at 1, 2, and 3 d of
      accumulation under bird cages; and (3) to assess the influence of 14-d freezing
      storage on the composition of manure when later exposed to 25 degrees C for 7 d
      as compared with fresh manure. All manure samples were collected from a layer
      house. Analyses performed on the manure samples included total Kjeldahl nitrogen,
      uric acid nitrogen, ammonia nitrogen, and urea nitrogen. In experiment 1, the
      storage methods most similar to fresh manure, in order of preference, were
      freezing, freeze-drying, acidification, and refrigeration. Thoroughly mixing
      manure samples and compressing them to 2 to 3 mm is important for the freezing
      and freeze-dried samples. In general, refrigeration was found unacceptable for
      nitrogen analyses. A significant effect (P < 0.0001) of time for refrigeration
      was found on uric acid nitrogen and ammonia nitrogen. In experiment 2, the total
      Kjeldahl nitrogen and uric acid nitrogen were significantly lower (P < 0.05) for
      1, 2, and 3 d of accumulation compared with fresh manure. Manure after 1, 2, and
      3 d of accumulation had similar nitrogen compositions. The results from
      experiment 3 show that nitrogen components from fresh manure samples and thawed
      samples from 14 d of freezing are similar at 7 d but high variability of nitrogen
      compositions during intermediate times from 0 to 7 d prevents the recommendation
      of freezing manure for use in subsequent experiments and warrants future
      experimentation. In conclusion, fresh poultry manure can be frozen for accurate
      subsequent nitrogen compositional analyses but this same frozen manure may not be
      a reliable substitute for fresh manure if a subsequent experiment is performed.

PMID- 19590066
TI  - Stocking density effects on broiler welfare: identifying sensitive ranges for
      different indicators.
AB  - Although stocking density is perceived as a topic of major importance, no
      consensus has been reached on what density would allow for good welfare. In the
      present study, the welfare of 4 replicates of birds stocked at 8, 19, 29, 40, 45,
      51, 61, and 72 broilers per pen (or 6, 15, 23, 33, 35, 41, 47, and 56 kg actually
      achieved BW/m(2)) was studied using 6 welfare indicators. Density did not affect
      bursa weight, mortality, or concentrations of corticosterone metabolites in
      droppings but did influence leg health (P = 0.015) and footpad and hock
      dermatitis (P < 0.001) and tended to influence fearfulness (P = 0.078). However,
      not every increase in density or group size, or both, led to poorer welfare for
      the affected indicators: leg health and fearfulness showed unexpected peaks at
      intermediate densities. Furthermore, the indicators were influenced at different
      densities: leg strength showed a steep decrease from 6 to 23 kg/m(2), hock
      dermatitis rose from 35 to 56 kg/m(2), and footpad dermatitis and fearfulness
      were only significantly higher at the highest density of 56 kg/m(2). No threshold
      stocking density above which all aspects of welfare were suddenly altered was
      found in this study. Instead, different aspects of welfare were influenced at
      different densities or group sizes, or both. Thus, evaluating the effects of
      stocking density on welfare as a whole would require either identification of
      acceptable levels for each separate indicator or a weighting of the indicators in
      an integrated welfare score. A tentative attempt to such an integration, made
      using equal weights for all parameters, showed a decrease in welfare as density
      increased (P < 0.001). The lowest 2 densities (6 and 15 kg/m(2)) scored better
      than most middle densities (23, 33, 35, and 47 kg/m(2)), whereas all densities
      scored better than the highest density (56 kg/m(2)).

PMID- 19590067
TI  - The effect of feeder space allocation on behavior of Hy-Line W-36 hens housed in
      conventional cages.
AB  - Insufficient feeder space for laying hens could increase competition at the feed
      trough, resulting in exclusion of low-ranking hens from the feeder. To test this
      hypothesis, the effects of feeder space allocation (FSA) on feeding behavior,
      aggression, feather scores, BW, and mortality were evaluated in a common
      commercial strain of egg-laying chickens. Beak-trimmed Hy-Line W-36 hens (n =
      480) were obtained as pullets at 16.5 wk of age and housed in conventional cages
      on 4 tiers. Five pullets/cage were housed at a stocking density of 434
      cm(2)/pullet and an FSA of 12.2 cm/pullet. After 1.5 wk of acclimation, baseline
      measurements were taken for 2 wk and then pullets were given either 5.8, 7.1,
      8.4, 9.7, 10.9, or 12.2 cm of feeder space/hen (16 cages/treatment). Feeding
      behavior was evaluated in each cage over a 24-h period each month. For each hen,
      percentage of time spent feeding and synchrony (mean number of additional hens
      feeding at the same time) were determined and scores were averaged for each cage.
      For each cage, feeder switching (number of observations in which hens changed
      from feeding to not feeding) and feeder sharing (probability that feeder access
      was equally distributed among all hens) were calculated. At monthly intervals,
      individual hens were weighed and their feathers scored using a 5-point scale on 8
      body regions. Data were analyzed using a repeated measures GLM incorporating
      cage, tier, FSA, and age of the hen. Hens with reduced feeder space spent less
      time feeding (P < 0.001), synchronized their feeding bouts to a lesser extent (P
      < 0.001), made fewer switches at the feeder (P < 0.001), and shared the feeder
      less (P < 0.001). However, feather scores, BW, and BW uniformity were not
      affected by FSA. There was almost no aggressive behavior and little mortality.
      These results demonstrate that Hy-Line W-36 hens did not respond to reduced
      feeder space by aggressively excluding cage-mates from the feeder but instead
      desynchronized their feeding behavior.

PMID- 19590068
TI  - Conjugative plasmid transfer between Salmonella enterica Newport and Escherichia
      coli within the gastrointestinal tract of the lesser mealworm beetle, Alphitobius
      diaperinus (Coleoptera: Tenebrionidae).
AB  - The objective of this study was to determine if conjugative transfer of
      antimicrobial resistance plasmids could occur between donor and recipient
      bacteria within the gastrointestinal tract of lesser meal-worm beetles, a common
      pest in poultry production facilities. In 3 replicate studies (n = 40 overall),
      beetles were allowed to feed for 2 h on brain heart infusion agar inoculated with
      a multidrug-resistant Salmonella enterica serotype Newport strain (SN11 that
      carried plasmid replicons A/C and N) at 1.0 x 10(8) cfu/mL. Beetles were surface
      disinfected and allowed to feed for 16 h on brain heart infusion agar inoculated
      with nalidixic acid- and rifampicin-resistant Escherichia coli JM109 at 9.0 x
      10(6) cfu/mL. After bacterial exposure, beetles were surface-disinfected,
      homogenized, and selectively plated for transconjugants. Serial dilutions were
      done for conjugation frequencies. In vitro filter conjugations were performed
      simultaneously with beetle conjugations. Transconjugants were produced in all
      beetles exposed to both donor and recipient bacteria. Ninety-five percent of the
      beetle and 100% of the in vitro filter transconjugants were positive for the N
      plasmid replicon. The A/C replicon, which was also detected in the SN11 donor
      strain, did not transfer in any of the conjugation studies. None of the
      transconjugants displayed resistance to extended-spectrum cephalosporins. The
      geometric mean conjugation frequency in the beetle gut was 1.07 x 10(-1). The
      average conjugation frequencies for the beetle gut were 2 logs higher than those
      for the filter conjugations 4.1 x 10(-3). This study demonstrates that horizontal
      transfer of antimicrobial resistance plasmids can occur between Salmonella and E.
      coli within the gut of beetles and that beetles may be used as an in vivo model
      to study resistance gene transfer.

PMID- 19590069
TI  - Furnished cage system and hen well-being: Comparative effects of furnished cages
      and battery cages on behavioral exhibitions in White Leghorn chickens.
AB  - The battery cage system is being banned in the European Union before or by 2012,
      and the furnished cage system will be the only cage system allowed after 2012.
      This study was conducted to examine the different effects of caging systems,
      furnished cages vs. battery cages, on bird behaviors. One hundred ninety-two 1-d
      old non-beak-trimmed Hy-Line W-36 White Leghorn chicks were reared using standard
      management practices in raised wire cages. At 19 wk of age, the birds were
      randomly assigned into battery cages or furnished cages. The battery cages were
      commercial wire cages containing 6 birds per cage, providing 645 cm(2) of floor
      space per birds. The furnished cages had wire floors and solid metal walls, with
      perches, a dustbathing area, scratch pads, and a nestbox area with a concealment
      curtain. Based on the company recommendations, 10 birds were housed per cage,
      providing a stocking density of 610 cm(2) of floor space per bird. Behavioral
      observations were conducted using the Noldus Observer software package. The birds
      were observed at 5-min intervals for the entire light period. The birds housed in
      battery cages had higher posture and behavioral transitions and increased time
      spent walking and performing exploratory behavior (P < 0.05, 0.01, respectively),
      which may indicate they were stressed, resulting in restlessness, whereas the
      birds housed in furnished cages had higher levels of preening (P < 0.05).
      Preening has been considered as a comfort behavior in birds. These results may
      suggest that furnished cages may be a favorable alternative system for housing
      birds by allowing them to perform certain natural behaviors.

PMID- 19590071
TI  - Novel avian leukosis virus-related endogenous proviruses from layer chickens:
      characterization and development of locus-specific assays.
AB  - During the course of evolution, vertebrate genomes have been invaded and
      colonized by retroviruses. In humans, for example, endogenous retroviruses (long
      terminal repeat elements) occupy roughly twice as much sequence space as
      essential genes. There are numerous reports in the literature implicating
      endogenous proviruses in the modulation of host physiology. The fact that many of
      these host-virus interactions take place in a proviral locus-specific manner
      speaks to the need for rapid assays for element profiling. This report deals with
      the identification of novel elements belonging to a family of endogenous
      retroviruses, designated ALVE, that reside in the genome of the chicken and that
      are closely related to exogenous avian leukosis viruses. The study of ALVE
      elements in the chicken genome serves as a model system for understanding the
      interplay between endogenous viruses and their vertebrate hosts in general,
      including humans. In this report, we present locus-specific, diagnostic PCR-based
      assays for 2 novel ALVE elements. In addition, we characterize the proviral
      structures and examine the genomic environments of both novel elements along with
      a previously described element known as ALVE-NSAC-3.

PMID- 19590070
TI  - Gene expression profiles of two B-complex disparate, genetically inbred Fayoumi
      chicken lines that differ in susceptibility to Eimeria maxima.
AB  - This study was conducted to compare the gene expression profiles, after Eimeria
      maxima infection, between 2 B-complex congenic lines of Fayoumi chickens that
      display differences in disease resistance and innate immunity against avian
      coccidiosis using cDNA microarray. When compared with uninfected controls using a
      cutoff of >2.0-fold alteration (P < 0.05), M5.1 demonstrated altered expression
      of 1 (downregulated), 12 (6 up, 6 down), and 18 (5 up, 13 down) mRNA at 3, 4, and
      5 d postinfection, respectively. In the M15.2 line, altered expression was
      observed in 6 (3 up, 3 down), 29 (11 up, 18 down), and 32 (8 up, 24 down)
      transcripts at the 3 time points, compared with uninfected controls. Comparison
      of the expression levels between M5.1 and M15.2 chickens after E. maxima
      infection revealed alterations in 32 (10 up, 22 down), 98 (43 up, 55 down), and
      92 (33 up, 59 down) mRNA at the 3 time points. Functional analysis using gene
      ontology categorized the genes exhibiting the different expression patterns
      between 2 chicken lines into several gene ontology terms including immunity and
      defense. In summary, transcriptional profiles showed that more gene expression
      changes occurred with E. maxima infection in the M15.2 than the M5.1 line. The
      most gene expression differences between the 2 chicken lines were exhibited at d
      4 and 5 after E. maxima infection. These results demonstrate that differential
      gene expression patterns associated with the host genetic difference in
      coccidiosis resistance provide insights into the host protective immune
      mechanisms and present a rational basis to target specific genes and gene
      products to bolster host defenses against avian coccidiosis.

PMID- 19590072
TI  - Screening of lactic acid bacteria toward their selection as a source of chicken
      probiotic.
AB  - In this study, 332 lactic acid bacteria of broiler gut origin were investigated
      as putative probiotic candidates. Sixty-two bacteria showed the highest
      aggregation while showing antibacterial effects against Salmonella Enteritidis,
      Salmonella Typhimurium, and Escherichia coli O78:K80. Enzymatic activities of the
      selected bacteria were examined. No lipase activity was detected, but all of them
      showed almost similar proteolytic activities. However, they had different amylase
      and phytase activities. Four of the 62 bacterial strains were selected as a
      result of aggregation and amylase tests. They were chosen for the following
      attributes: high cell surface hydrophobicity, co-aggregation, and resistance to
      bile salts and also acidic conditions. Finally, Lactobacillus crispatus was
      selected as a source of potential probiotic because of its predominant
      characteristics in comparison to the other isolated strains from the
      gastrointestinal tract of chickens. This study has provided a good arrangement of
      rapid methods for screening a high number of bacteria: a series of beneficial
      tests that are used together for the first time on chickens, and not any other
      animals.

PMID- 19590073
TI  - The intracellular localization and oligomerization of chicken invariant chain
      with major histocompatibility complex class II subunits.
AB  - Invariant chain (Ii) binds to MHC class II (MHCII) to assemble a nonamer in the
      endoplasmic reticulum. Major histocompatibility complex class II-associated Ii
      peptide (CLIP) that occupies the peptide binding groove of MHCII prevents MHCII
      molecules from loading with endogenous antigens. We used the green or red
      fluorescent protein-fused Ii or MHCII subunits to detect the intracellular
      localization and oligomerization of chicken Ii with single chicken MHCII
      subunits. Our results indicated that chicken Ii associates with single MHCII
      subunits and formed oligomers with MHCII subunits. The Ii mutant with a deleted
      CLIP sequence blocks the association with single MHCII subunits, but exchanging
      CLIP with the Newcastle disease virus F(343) epitope restores this association.
      Thus, MHCII polymer assembly is not blocked as long as the basic steric molecular
      structure of Ii is maintained, and different binding models exist in different
      species or MHCII isotypes.

PMID- 19590074
TI  - Rous sarcoma growth in lines congenic for major histocompatibility (B) complex
      recombinants.
AB  - Rous sarcoma virus (RSV)-induced tumor growth was examined in congenic lines of
      chickens with different major histocompatibility (B) complex recombinant
      haplotypes on the highly inbred line UCD 003 (B17B17) genetic background. Males
      bearing an individual B complex recombinant were mated to UCD 003 females
      followed by 10 backcross generations. Matings among heterozygotes for each
      recombinant produced homozygous chickens estimated to contain 99.9% of the line
      UCD 003 background genome. The 5 lines having distinct serologically identified
      MHC recombinant haplotypes, which arose from separate recombinational events,
      were as follows: 003.R1, 003.R2, 003.R4, 003. R5, and 003.R6. Chicks from each of
      the recombinant lines were challenged with 10 pfu subgroup A RSV at 6 wk of age.
      Tumors were scored for size 6 times over 10 wk postinoculation. Each bird was
      assigned a tumor profile index (TPI) based on the 6 tumor size scores. Hatch and
      B genotype were main effects in the statistical analysis. Least squares ANOVA was
      used to evaluate rank-transformed TPI values and mean tumor sizes through a
      repeated measures design. Tumor growth and TPI values were greater for 003.R1 and
      003.R4 chickens than for the other 3 congenic lines. Among serologically similar
      recombinants 003.R2 and 003.R4, higher tumor growth and TPI in 003.R4 indicate
      unique genetic variation affecting RSV tumors compared with 003.R2. The similar
      tumor growth of 003.R5 and 003.R6 chickens, which have BF/BL21 but different BG
      regions, demonstrated no BG effect on RSV tumors.

PMID- 19590075
TI  - Preparation and immune activity analysis of H5N1 subtype avian influenza virus
      recombinant protein-based vaccine.
AB  - Avian influenza is a severe disease among farmed poultry and free-living birds
      and a constant threat to the commercial chicken industry around the world.
      Hemagglutinin (HA) is the major immunogen on the envelope of influenza A virus
      and is the predominant inducer of neutralizing antibody. To obtain the bioactive
      antigen proteins in large quantities, a new protein expression vector pBCX was
      constructed, which is based on the pET32a vector. The HA gene of the H5N1 subtype
      of avian influenza virus (AIV) was inserted into the pBCX vector and expressed
      efficiently in Escherichia coli BL21 (DE3). Fused expression of the exogenous
      gene and msyB produced a 97-kDa msyB-HA fusion protein. Sodium dodecyl sulfate
      PAGE combined with scanning analysis demonstrated that the msyB-HA fusion protein
      accounted for 29.5% of the total bacterial protein, 90.5% being soluble. The msyB
      HA fusion protein was purified with nondenaturing 50% Ni-NTA column
      chromatography, and the result showed that 24 mg of purified msyB-HA fusion
      protein could be obtained from 1 L of induced expression bacterial culture
      medium. The comparative results in the present study showed that pBCX was
      superior to pET32a as a protein expression vector. Western blotting showed the
      recombinant msyB-HA (rHA) to have better antigenic activity, which may be the
      result from the better posttranslation protein modification and folding in the
      pBCX expression system. With the rHA fusion protein as antigen, we successfully
      prepared and screened specific monoclonal antibodys against the H5N1 subtype AIV,
      which indicated that the rHA had antigen epitopes and biofunctions. The immune
      test confirmed that the rHA protein vaccine could also induce high neutralizing
      antibodies, and the AIV challenge test proved that the rHA protein-based vaccine
      could prevent the corresponding infection. This study demonstrates that the
      recombinant HA protein produced by the pBCX expression system could be used as a
      recombinant protein-based vaccine and has potential for further development for
      diagnosis.

PMID- 19590076
TI  - Effect of citric acid, avilamycin, and their combination on the performance,
      tibia ash, and immune status of broilers.
AB  - The aim of this study was to determine the effect of the supplementation of an
      organic acid (citric acid), antibiotic growth promoter (avilamycin), and their
      combination for a period of 35 d on the growth, feed efficiency, carcass yield,
      tibia ash, and immune status of broilers. One hundred sixty 1-d-old broiler
      chicks (Hubbard Classic) were randomly distributed into 4 groups with 4 replicate
      cages having 10 birds in each. A corn-soybean-based diet was used as the basal
      diet (control). The basal diet was supplemented with an organic acid (citric
      acid, 0.5%), an antibiotic growth promoter (avilamycin, 0.001%), and their
      combination in other groups. The highest BW was attained in citric acid-fed
      chicks (1,318 g), which was significantly (P < 0.05) higher than control chicks
      (1,094 g) or avilamycin-fed chicks (1,217 g). The combination-fed chicks showed
      similar weight (1,246 g) as citric acid- or avilamycin-fed chicks (P > 0.05).
      Total feed intake was higher in citric acid-fed chicks compared with antibiotic
      supplemented chicks. The addition of citric acid improved feed conversion
      efficiency (g of weight gain/ kg of feed intake) significantly (P < 0.05)
      compared with control chicks or its combination with avilamycin. Higher carcass
      weights were found in chicks fed the combination diet. Supplementation of citric
      acid increased tibia ash percentage significantly (P < 0.05) compared with
      controls. Addition of citric acid reduced the pH of the formulated diets. An
      improvement of immune status was detected by densely populated immunocompetent
      cells in the lamina propria and submucosa of cecal tonsils and ileum and also in
      the cortex and medulla of bursa follicles in citric acid-supplemented chicks.
      Supplementation of citric acid at 0.5% in the diet had positive effects on
      growth, feed intake, feed efficiency, carcass yield, bone ash, and immune status
      of broilers. Therefore, citric acid might be a useful additive instead of
      antibiotic growth promoters such as avilamycin, considering performance and
      health status of broilers.

PMID- 19590077
TI  - Impaired intestinal mucosal immunity in specific-pathogen-free chickens after
      infection with very virulent infectious bursal disease virus.
AB  - Diarrhea is one of the most important clinical side effects that occurs in
      chickens after infection with bursal disease virus. However, the kinetics of the
      intestinal mucosal immune parameters in infectious bursal disease virus (IBDV)
      infected birds remains unclear. Forty-five specific-pathogen-free chickens were
      randomly divided into 2 groups [30 chickens in the very virulent IBDV (vvIBDV)
      infected group and 15 chickens in the control group] to determine the effect of
      vvIBDV infection on intestinal mucosal immunity. All chickens were raised in
      negative-pressure isolators and fed the same diet. Results indicate that severe
      histologic lesions were observed in the intestinal tract in the vvIBDV-infected
      group, and the villus heights of the duodenum, jejunum, and ileum were decreased
      after vvIBDV infection (P < 0.01 or P < 0.05). The number of intestinal
      intraepithelial lymphocytes, mast cells, and goblet cells decreased significantly
      in the vvIBDV-infected group compared with the control (P < 0.01 or P < 0.05) on
      d 1, 2, and 3 postchallenge with vvIBDV. Very virulent IBDV infection reduced the
      expression of each fragment of intestinal secretory IgA at all 3 time points.
      Intestinal alkaline phosphatase decreased dramatically on d 2 and 3 postchallenge
      with vvIBDV. Taken together, these results indicate that vvIBDV infection
      contributes to considerable damage to the normal structure of the intestine and
      intestinal mucosal immune parameters of specific-pathogen-free chickens. Our
      research helps to increase an understanding of the pathogenesis of diarrhea
      induced by vvIBDV infection. These findings provide new insights into the
      pathogenesis and pathophysiology of vvIBDV infection.

PMID- 19590078
TI  - Dietary arginine stimulates humoral and cell-mediated immunity in chickens
      vaccinated and challenged against hydropericardium syndrome virus.
AB  - The effects of dietary supplement of arginine on protective humoral and cell
      mediated immune responses of broiler chicks vaccinated and challenged against
      hydropericardium syndrome virus (HPSV) were investigated and compared with those
      of 2 reference drugs (cyclophosphamide and cyclosporine). Percentage ratios of
      lymphoid organs (bursa, spleen, and thymus) to BW, postvaccination and challenge
      serum antibody responses to HPSV, cutaneous basophil hypersensitivity reaction,
      peripheral lymphoproliferation, postchallenge detection of HPSV in the tissues of
      infected birds, and ability of chicks to resist virulent HPSV challenge were the
      parameters utilized to determine the effects of arginine on protective immune
      responses of chicks. A total of 600 chicks were used in this study. Arginine
      supplemented chicks showed significant (P < 0.05) stimulation of
      lymphoproliferation and cutaneous basophil hypersensitivity reactions compared
      with untreated control chicks. Similarly, significantly higher body and lymphoid
      organ weights were (P < 0.05) recorded in arginine-supplemented chicks compared
      with untreated control chicks. The highest survival rate was recorded in arginine
      supplemented HPS-vaccinated chicks compared with immune-suppressed
      (cyclophosphamide- and cyclosporine-treated and HPS-vaccinated chicks) and
      untreated unvaccinated control chicks after virulent HPSV challenges.
      Postchallenge tissue samples from arginine-supplemented and HPS-vaccinated chicks
      yielded negligible HPSV detections by virus isolation in cell culture or PCR
      method, or both, compared with untreated control chicks. Thus, it was concluded
      that dietary supplementation of arginine had beneficial effects on humoral and
      cell-mediated immune responses of broiler chicks against HPSV.

PMID- 19590079
TI  - Flock-level prevalence of Clostridium colinum in broiler flocks with digestive
      disease in Jordan by polymerase chain reaction.
AB  - A cross-sectional study was conducted from May to September of the year 2008 in
      broiler flocks in the southern and northern area of Jordan, to determine the
      flock-level prevalence of Clostridium colinum infection. Intestinal swabs were
      collected from 170 broiler flocks and tested by PCR. Among the study population,
      20 flocks in both areas (11.8%, 95% confidence interval: 10 to 22%) were positive
      for C. colinum infection. The prevalence of positive intestinal samples in the
      southern and northern area of Jordan were 4.7 and 7.1%, respectively, which was
      statistically significant (chi(2) = 3.9 df = 1, P = 0.0482). It is recommended to
      conduct further epidemiologic studies to determine risk factors and to evaluate
      the economic consequences of the C. colinum infection in the region.

PMID- 19590080
TI  - Efficiency of a Lactobacillus plantarum-xylanase combination on growth
      performances, microflora populations, and nutrient digestibilities of broilers
      infected with Salmonella Typhimurium.
AB  - Three experiments were performed to assess the ability of a Lactobacillus
      plantarum probiotic combined with a xylanase to reduce the effects of Salmonella
      Typhimurium infection in broiler chickens from 1 to 30 or 42 d of age. Chicks
      were challenged at 3 d of age with 10(8) or 10(5) cfu Salmonella
      Typhimurium/chick. Four diets were studied: a wheat-based diet (C+) supplemented
      with 0.1 g/kg of xylanase (E) or 10(6) cfu/g of L. plantarum (P), or both (PE).
      Uninfected chicks fed the C diet were used as negative control (C-). Six or 8
      chicks were housed per cage with 9 cages/treatment. Growth performance and feed
      conversion ratio (FCR) were recorded weekly. In experiment 1, bacterial
      enumeration in ceca was achieved using the fluorescent in situ hybridization
      technique. Salmonella enumeration was realized in excreta by microbiological
      cultures (experiments 2 and 3). Nutrient digestibilities and AME(n) were
      determined in experiment 3 from d 35 to 39. Infection with Salmonella Typhimurium
      led to a significant decrease in the daily weight gain (DWG) by 23.6 to 32.8%,
      whereas FCR was increased by 1.0 to 19.7%. Chickens fed the PE diet showed
      significantly improved performance in comparison with C+ birds (DWG: +12.5% in
      experiment 1; FCR: -2.1 to 8.6%), and in comparison with the P and E treatments
      (DWG: +6.3 to 8.3% in experiment 1; FCR: -2.7 to 6.4%). In experiment 3, the FCR
      was significantly improved by 3% with the PE diet in comparison with C- chickens.
      The PE combination tended to restore a microflora similar to that of uninfected
      broilers, whereas the P and E diets had less of an effect on the profile of
      bacterial communities. At slaughter age, Salmonella contamination was reduced by
      2.00 and 1.85 log colony-forming units for the E and PE treatment, respectively.
      The PE diet significantly reduced the crude fat digestibility by 9.2%, in
      comparison with the C+ chickens. These results suggest that the combination
      between L. plantarum and a xylanase as feed additive could be effective for
      reduction of the detrimental effect after Salmonella Typhimurium infection of
      broilers.

PMID- 19590081
TI  - Experimental approach to optimize phytate phosphorus utilization by broiler
      chickens by addition of supplements.
AB  - Supplementation of 1alpha-hydroxycholecal-ciferol (1alpha-OHD(3)), phytase, and
      Ca levels has been shown to influence phytate P utilization. Two experiments were
      conducted with 1- to 16-d broilers to investigate the interactions between the
      effects of 1alpha-OHD(3), phytase, and Ca on phytate P utilization. In experiment
      1, the birds were randomly allocated to 13 treatments with 6 levels of 1alpha
      OHD(3) from 0 to 11microg/kg, with and without 500 U/kg of phytase supplemented
      to P-deficient diet. A positive control diet, adequate in Ca and P, was included.
      In experiment 2, a 3-dimensional rotatable design with 5 levels each of 1alpha
      OHD(3), phytase, and Ca was implemented. Supplementation of 1alpha-OHD(3) and
      phytase increased phytate P utilization, as indicated by an increase in bone ash,
      phytate P disappearance, and BW. In experiment 1, no interaction between the
      1alpha-OHD(3) and phytase effects was determined for any criteria, except for the
      incidence of P rickets. However, the second experiment showed that there were
      interactions between the 3 factors (1alpha-OHD(3), phytase, and Ca). The
      probabilities that observed variation in the 3-way interaction for measured
      criteria that were due to chance are: BW gain = 0.1364, G:F = 0.11, bone ash
      percentage = 0.0278, milligrams of bone ash/tibia = 0.0909, Ca rickets = 0.9394,
      P rickets = 0.4892, tibial dyschondroplasia = 0.5927, and phytate P disappearance
      = 0.1126. The equations obtained from the regression models were used to generate
      contour-surface plots. The percentage of bone ash data indicated that low Ca,
      high phytase, and high 1alpha-OHD(3) levels were needed to optimize phytate P
      utilization. The results of this study show that this experimental design may be
      utilized to identify the best levels of nutrients to add to a diet where complex
      3-way interactions exist affecting several criteria. The equations may be used to
      optimize performance based on desired levels of performance and the costs of the
      inputs.

PMID- 19590082
TI  - Wheat starch digestion rate affects broiler performance.
AB  - Two experiments were conducted to determine the differences in starch digestion
      rate (KDS) among wheats from different cultivars and origins and to verify if
      chickens would benefit from a certain digestion rate of starch. In the first
      experiment, 192 chickens (21 d) were assigned to 4 diets containing 55% of each
      wheat sample (3 cultivars, one of them from 2 origins). Starch and protein
      digestion were calculated from the remaining starch and protein in 4 segments of
      the small intestine and in excreta, using chromic oxide as a marker. Mean
      retention time was measured in each segment, which enabled calculations of
      digestion rates. In the second experiment, 2,600 chickens were assigned to 5
      isoenergetic and isonitrogenous diets (with KDS from 1.80 to 2.56 h(-1)) and
      growth performance was determined (1 to 34 d). In 3 treatments, dietary starch
      was provided each by the wheat cultivars (same origin), whereas in the other 2
      treatments, 25 and 50% of the wheat starch with the highest KDS was substituted
      by pea starch. Clostridium perfringens and Lactobacillus in the cecal chyme and
      glucose in the blood (glycemic index) were measured in broilers at d 19 and 25,
      respectively. Starch was gradually digested along the small intestine, mainly in
      the jejunum (48.5 and 80.4% at proximal and distal jejunum) where the largest
      differences among wheat samples were found. Starch digestion rate varied with
      origin (from 1.96 to 2.56 h(-1)) and cultivar (from 2.17 to 2.56 h(-1)). Crude
      protein digestion rate (average 2.21 h(-1)) was not affected by either cultivar
      or origin. Broiler growth and feed conversion ratio improved in a quadratic way
      with KDS. The maximum broiler performance was observed with KDS around 2.2 h(-1).
      Blood glucose response (glycemic index) was not affected by KDS; therefore, it
      cannot be used to predict broiler performance. In conclusion, the rate of starch
      digestion varies among wheats, depending on both genetic and environmental
      conditions of the grain, and affects broiler performance.

PMID- 19590083
TI  - Digestible lysine requirements of male and female broilers from fourteen to
      twenty-eight days of age.
AB  - There is little research data available on the digestible Lys requirement of
      broilers from 2 to 4 wk of age. Two experiments were conducted to determine the
      digestible Lys requirements of male and female Ross x Ross TP16 broilers from 14
      to 28 d. Two diets (dilution and summit) consisting of corn, soybean meal,
      poultry by-product meal, and peanut meal were formulated to be adequate in all
      other amino acids. The dilution and summit diets were blended to create 9
      titration diets. A control diet containing adequate Lys was used for comparison
      with the titration diets. A true Lys digestibility assay was conducted with
      cecectomized roosters to determine the values for the dilution (low) and summit
      (high) diets. True digestible Lys of the low and high dose-response diets were
      determined to be 0.84 and 1.21%, respectively. Body weight gain, feed intake,
      digestible Lys intake, digestible Lys intake:BW gain, feed conversion, and
      mortality were assessed during experimentation. Digestible Lys requirements were
      estimated using a quadratic broken-line model and a quadratic regression equation
      based on 95% of the optimum response. In experiment 1, the digestible Lys
      requirement for male Ross x Ross TP16 broilers was determined to be between 1.07
      and 1.09% and 1.10 and 1.15%, for BW gain and feed conversion, respectively. In
      experiment 2, the digestible Lys requirement for female Ross x Ross TP16 broilers
      was estimated as 0.98% for BW gain determined with a quadratic broken-line model
      and 1.03 and 0.99% for feed conversion, respectively, using a quadratic
      regression equation based on 95% of the optimum response and the quadratic broken
      line model. Digestible Lys requirements for male and female Ross x Ross TP16
      broilers were estimated at 1.10 and 1.00%, respectively, based upon BW gain and
      feed conversion averaged for both statistical models.

PMID- 19590084
TI  - Mitochondrial proton leak kinetics and relationship with feed efficiency within a
      single genetic line of male broilers.
AB  - Studies were conducted to assess proton leak kinetics (proton conductance) in
      breast muscle mitochondria isolated from broiler breeder males within a single
      genetic line exhibiting either high (HFE) or low (LFE) feed efficiency. Proton
      leak kinetics were determined by simultaneously measuring mitochondrial membrane
      potential and state 2 (resting) respiration rate in breast muscle mitochondria as
      succinate oxidation was progressively decreased by malonate. Control proton
      conductance was similar in HFE and LFE mitochondria and decreased to a similar
      extent in both groups in response to BSA. Although treatment of mitochondria with
      Glu or guanosine diphosphate had no effect, retinal increased and
      carboxyatractylate alone or in combination with Glu decreased proton conductance
      relative to control proton conductance in both HFE and LFE mitochondria. After
      treatment with either guanosine diphosphate or carboxyatractylate alone, proton
      conductance was lower in HFE compared with LFE mitochondria. With the exception
      of BSA, proton conductance in HFE mitochondria after the various chemical
      treatments was either less than or equal to, and never greater than, proton
      conductance in the LFE mitochondria. The results suggest that there are subtle
      differences in membrane characteristics (e.g., lipids, integral membrane
      proteins) that affect proton conductance in broiler muscle mitochondria that may
      in turn play a role in the phenotypic expression of feed efficiency.

PMID- 19590085
TI  - Isolation and characterization of virulent bacteriophages against Escherichia
      coli serogroups O1, O2, and O78.
AB  - The goal of this study was to isolate and characterize a more complete set of
      phages that are active against Escherichia coli serogroups O1, O2, and O78, the
      main causative agents of avian colibacillosis. A mixture of E. coli (O1:K1),
      (O2:K1), and (O78:K80) was used as a host to isolate phages from wastewater and
      fecal samples from poultry processing plants. Seven phages were isolated; only 2
      of them, EC-Nid1 and EC-Nid2, were selected for further characterization. It was
      found that EC-Nid1 and EC-Nid2 had icosahedral heads, necks, and contractile
      tails with tail fibers and therefore belonged to Myoviridae. The phages had
      genome sizes of 67.06 to 68.04 kb and they lysed all tested strains of E. coli
      serotype O1, O2, and O78. The 2 phages were resistant to pH 5 to 9, and phage EC
      Nid2 was slightly more resistant to acid and alkali environments. Two major
      protein bands were indicated in EC-Nid (A and D); band D at 45 kDa was a major
      coat protein and band A was identified as a homolog of endo-N
      acetylneuraminidase. It was concluded that phage EC-Nid1 and EC-Nid2 are highly
      active against O1, O2, and O78 colibacillosis strains.

PMID- 19590086
TI  - Higher incorporation of heterologous chicken immunoglobulin Y compared with
      homologous quail immunoglobulin Y into egg yolks of Japanese quail (Coturnix
      japonica).
AB  - In avian species, blood IgY is selectively incorporated into the yolks of
      maturing oocytes, although the precise mechanism is poorly understood. Our
      previous study showed that 22% of i.v.-injected heterologous chicken IgY (cIgY)
      was incorporated into egg yolks of Japanese quail (Coturnix japonica). However,
      it is not known whether homologous quail IgY (qIgY) can be more efficiently
      incorporated into quail egg yolks than cIgY. Therefore, we compared the uptakes
      of qIgY and cIgY i.v. administered into quail egg yolks and further characterized
      the uptakes of these 2 antibodies into quail ovarian follicles. Quail IgY and
      cIgY purified from the blood of the respective bird were labeled with
      digoxigenin, and their uptakes into quail egg yolks were determined by ELISA.
      Unexpectedly, total incorporation of the injected qIgY was only one-third of that
      of cIgY, although much more qIgY was left in blood compared with cIgY, suggesting
      that qIgY is the less preferable antibody as a transport ligand into quail egg
      yolks. On the other hand, deposition of the qIgY into heart, lung, liver, spleen,
      kidney, and ovarian follicular membrane was markedly higher than that of cIgY.
      Amino acid sequence analysis of 3 peptides derived from the trypsin-digested qIgY
      heavy chain revealed low homology between qIgY and cIgY. In conclusion, our
      results show that heterologous cIgY is more efficiently incorporated into quail
      egg yolks than homologous qIgY, possibly due to a distinctive antibody transport
      system existing in oocytes. The present results also may provide a new strategy
      for delivering useful proteinaceous substances into egg yolks in an attempt to
      produce designer eggs.

PMID- 19590087
TI  - Prostaglandin F(2alpha) receptor in the neurohypophysis of hens.
AB  - To elucidate whether the receptor for prostaglandin (PG) F(2alpha), one of PG,
      exists in the neurohypophysis in hens and whether the binding of receptor changes
      with relation to oviposition, the PGF(2alpha) binding component in the membrane
      fraction of the neurohypophysis of laying hens was analyzed by radioligand
      binding assay using [5,6,8,9,11,12,14,15(n)-(3)H]PGF(2alpha). The binding
      component had characteristics of a receptor such as binding specificity, high
      affinity, and limited capacity for PGF(2alpha). Scatchard analysis indicated that
      the binding site was of a single class. The binding capacity of the receptor was
      smaller in laying hens than in nonlaying hens, whereas the binding affinity was
      not significantly different between these hens. When non-laying hens received an
      i.m. injection of estradiol-17beta or progesterone (0.5 mg/hen), the specific
      binding of the PGF(2alpha) receptor in the neurohypophysis was decreased. In
      laying hens, the specific binding decreased and the blood arginine vasotocin
      (AVT) concentration increased just after oviposition but did not change during a
      24-h day in nonlaying hens. An i.v. injection of PGF(2alpha) (2 microg/hen)
      induced oviposition and caused an increase in the blood AVT concentration with a
      decrease in the specific binding of PGF(2alpha) receptor. The present study
      suggests a possibility that PGF(2alpha) may directly cause the AVT release from
      the neurohypophysis at oviposition time in hens.

PMID- 19590088
TI  - Effects of amylin on bone development and egg production in hens.
AB  - Amylin is a member of the calcitonin family of hormones cosecreted with insulin
      from the pancreatic beta-cells that can act as an osteoblast mitogen and as an
      inhibitor of bone resorption in mice and humans. The aim of this study was to
      investigate the role of amylin on bone formation and some egg parameters in hens.
      The study was performed in 60 hens aged 10 wk. Thirty hens constituting the
      treatment group were s.c. injected with amylin at a 75 microg/kg dose every other
      day. The remaining hens were used as the control group. Five birds from the
      treatment and control groups were slaughtered at 14, 16, 18, and 20 wk of age and
      serum and bone parameters were compared between the treatment and control groups.
      The remaining 20 hens were fed without any amylin injection until 35 wk. All hens
      at the end of the 35th week were slaughtered and then serum, bone, and egg
      parameters were assessed. In the treatment group, bone calcium levels increased,
      whereas serum calcium levels decreased. This dose of amylin also increased the
      cortical width of tibiotarsuses in hens. Eggshell thickness was found thicker in
      the treatment group than in the control group. Overall, the results of this study
      suggest that amylin may stimulate the bone and eggshell quality by increasing
      calcium uptake from the bloodstream and may influence the sustainability of yield
      in hens.

PMID- 19590089
TI  - Transforming growth factor-beta1-induced satellite cell apoptosis in chickens is
      associated with beta1 integrin-mediated focal adhesion kinase activation.
AB  - Transforming growth factor-beta1 (TGF-beta1) induces apoptosis in many types of
      cells. The cell adhesion receptor, beta1 integrin subunit, prevents apoptosis and
      may be involved in TGF-beta1-induced muscle cell apoptosis. In the current study,
      chicken primary satellite cells, myogenic precursors, were used to investigate
      the apoptotic effect of TGF-beta1 on muscle cells. The data from the current
      study showed that the addition of exogenous TGF-beta1 reduced beta1 integrin
      expression and altered its localization. Treatment of the satellite cells with
      TGF-beta1 increased the number of apoptotic cells indicated by annexin-V using
      flow cytometry. The number of caspase-positive cells was increased in the TGF
      beta1-treated immunostained cells, which supported that TGF-beta1 induced
      satellite cell apoptosis. It has been shown that beta1 integrin is involved in
      muscle cell survival. In response to the activation of beta1 integrin, focal
      adhesion kinase (FAK) phosphorylates tyrosine at residue 397 and activates cell
      survival signal transduction. The phosphorylation of FAK was significantly
      reduced from 30 min to 4 h after TGF-beta1 treatment during both satellite cell
      proliferation and differentiation. These data suggested that the apoptotic effect
      of TGF-beta1 on satellite cells is likely associated with a beta1 integrin
      mediated FAK signaling pathway during satellite cell proliferation and
      differentiation.

PMID- 19590090
TI  - Comparison of the total amount of eggshell pigments in Dongxiang brown-shelled
      eggs and Dongxiang blue-shelled eggs.
AB  - Based on the knowledge of the heme bio-synthetic and metabolic pathway and the
      structures of biliverdin and protoporphyrin, experiments were carried out to
      compare the difference between the total quality of eggshell pigments in blue
      shelled eggs and brown-shelled eggs from the same population (Dongxiang, China)
      and to analyze the correlation between the quantity of protoporphyrin and
      biliverdin in the 2 kinds of eggshells. It was found that there was no
      significant difference between the total quantity of eggshell pigments in
      Dongxiang blue-shelled eggs and Dongxiang brown-shelled eggs (P = 0.9006), and a
      highly significant positive correlation between the quantity of protoporphyrin
      and biliverdin in blue eggshells (P < 0.01) and a significant positive
      correlation between the quantity of protoporphyrin and biliverdin in brown
      eggshells (P < 0.05). These results suggested that eggshell protoporphyrin and
      eggshell biliverdin probably derived from common precursor material.

PMID- 19590091
TI  - Omega-3-enriched broiler meat: 3. Fatty acid distribution between triacylglycerol
      and phospholipid classes.
AB  - Consumers are becoming more aware of the effect of the food they eat on their
      health. One of the ways they hope to reduce their risk of cardiovascular disease
      is by consuming more foods enriched with n-3 polyunsaturated fatty acids (PUFA).
      Due to the high content of alpha-linolenic acid (LNA), dietary flaxseed is a good
      source for increasing n-3 PUFA in poultry meat. A study was conducted with 2
      primary objectives: to establish the distribution of n-3 PUFA between
      triacylglycerol (TAG) and phospholipid of broiler chicken breast and thigh meat
      and to determine the duration of dietary flaxseed supplementation required to
      ensure a level of n-3 PUFA of 300 mg per 100 g of meat necessary to label meat as
      a source of n-3 PUFA. This experiment was conducted as a 2 x 8 factorial, with 2
      dietary levels of ground flaxseed (10 and 17%) and 8 durations of dietary
      flaxseed before processing [0 (control), 4, 8, 12, 16, 20, 24, and 35 d]. A total
      of 128 Ross x Ross 308 mixed-sex broilers were evaluated to 35 d of age. Breast
      and thigh meat fatty acid composition was analyzed on duplicate samples of ground
      meat pooled from 8 birds per treatment. Broken-stick analysis was used to
      estimate the duration required to achieve 300 mg of n-3 PUFA per 100 g of breast
      meat. Results clearly indicated that LNA was mainly deposited in the TAG fraction
      of both breast and thigh meat. Enriching the chicken breast meat with 300 mg of n
      3 PUFA per 100 g of meat was achieved in 11.3 and 26.2 d with a 17 and 10% level
      of flaxseed in diet, respectively. Although a significant increase of n-3 long
      chain PUFA (20:5n-3, 22:5n-3, and 22:6n-3) was found in the phospholipid and TAG
      fraction of both tissues, the concentration of these functional components was
      low. More than 95% of n-3 PUFA enrichment was due to LNA.

PMID- 19590092
TI  - Innovations in the development of healthier chicken sausages formulated with
      different lipid sources.
AB  - Long-chain polyunsaturated n-3 fatty acids are critical nutrients for human
      health and the fortification of foods with these fatty acids is an important
      emerging area from the commercial and academic point of view. Development,
      characterization, and changes during refrigerated vacuum storage of low-fat
      chicken sausages formulated with preemulsified squid oil were examined and
      compared with those formulated with beef tallow. Physicochemical analysis and
      process yield after heat treatment were determined; the heat-treated sausages
      were evaluated by purge loss, color, texture, microstructure by SEM, microbial
      counts, fatty acid profile, lipid oxidation, and sensory analysis during
      refrigerated vacuum storage. Process yield of both formulations was higher than
      97% and purge losses during storage were lower than 7%. Purge losses of oil
      formulated sausages were lower than those with beef tallow. Sausages with squid
      oil resulted in higher lightness, lower redness and yellowness, and lower texture
      profile analysis parameters than the formulation prepared with beef tallow.
      Microstructure of both formulations was similar, except for the fat droplets that
      microscopic observations showed in the sausages made with beef tallow. Low lipid
      oxidation was detected in formulation with squid oil due to the the combination
      of ingredients and storage conditions. Microbial counts of both products were
      less than 5 log cfu/g at the end of 90 d of storage. The sausage formulated with
      squid oil presented more than 30 and 40 g/100 g of monounsaturated and
      polyunsaturated fatty acids, respectively. Docosahexaenoic acid was the
      predominant polyunsaturated fatty acid, followed by eicosapentaenoic acid and
      linoleic acid. Both products showed safe sanitary conditions, good sensory
      acceptability, and presented very good stability and quality attributes, but
      sausages formulated with squid oil showed a better fatty acid profile according
      to nutritional criteria.

PMID- 19590093
TI  - Nisin, rosemary, and ethylenediaminetetraacetic acid affect the growth of
      Listeria monocytogenes on ready-to-eat turkey ham stored at four degrees Celsius
      for sixty-three days.
AB  - The objectives of this study were to determine the anti-Listeria and general
      antimicrobial properties of nisin, rosemary, and EDTA alone and in combination on
      Listeria monocytogenes inoculated on ready-to-eat vacuum-packaged diced turkey
      ham and to ascertain the effects of the treatments on pH and objective color. The
      turkey hams were cut into 0.5-cm pieces, inoculated with a L. monocytogenes
      cocktail containing 5 strains of the bacterium, and treated with either no
      treatment and no inoculum (negative control), inoculum only (positive control),
      0.5% nisin, 20 mM EDTA, 1% rosemary, 0.5% nisin + 20 mM EDTA, 0.5% nisin + 1%
      rosemary, 0.5% nisin + 20 mM EDTA + 1% rosemary, or 20 mM EDTA + 1% rosemary. All
      samples were vacuum-packaged, stored for 63 d at 4 degrees C +/- 1 degrees C, and
      analyzed at 1-wk intervals for total aerobes, L. monocytogenes, lactic acid
      organisms, pH, and objective color. Nisin, nisin with rosemary, nisin with EDTA,
      and nisin with rosemary and EDTA treatments reduced (P < 0.05) L. monocytogenes
      counts by 4.42, 4.20, 3.73, and 4.11 log cfu/g when compared with the positive
      control, respectively, on d 0. Listeria monocytogenes counts remained less than
      2.75 log cfu/g for all hams treated with nisin. The EDTA and rosemary treatments
      alone and in combination were ineffective in inhibiting growth of L.
      monocytogenes. Although none of the treatments completely eliminated L.
      monocytogenes, the results indicated that ready-to-eat turkey ham can have
      significantly decreased L. monocytogenes when treated with nisin alone or in
      combination with rosemary or EDTA, or both.

PMID- 19590094
TI  - Production of an egg yolk antibody against Parietaria judaica 2 allergen.
AB  - Specific antibodies are essential tools for studying proteins as well as for
      diagnostic research in biomedicine. The egg yolk of immunized chicken is an
      inexpensive source of high-quality polyclonal antibodies. The 12-kDa Parietaria
      judaica 2 allergen was expressed as a fusion protein and was used to immunize
      Leghorn chickens. In this paper, we show, using 2-dimensional gel electrophoresis
      and immunoblotting, that chicken antibodies raised against a recombinant allergen
      can be used to recognize similar proteins from a pollen raw extract. Allergen
      identity was confirmed by nanoLC-nanospray-tandem mass spectrometry analysis. Our
      data demonstrate for the first time that a synergistic combination of molecular
      biology, 2-dimensional PAGE, and use of nonmammalian antibodies represents a
      powerful tool for reliable identification of allergens.

PMID- 19590095
TI  - Minimal promoter systems reveal the importance of conserved residues in the B
      finger of human transcription factor IIB.
AB  - The "B-finger" of transcription factor IIB (TFIIB) is highly conserved and
      believed to play a role in the initiation process. We performed alanine
      substitutions across the B-finger of human TFIIB, made change-of-charge mutations
      in selected residues, and substituted the B-finger sequence from other organisms.
      Mutant proteins were examined in two minimal promoter systems (containing only
      RNA polymerase II, TATA-binding protein, and TFIIB) and in a complex system,
      using TFIIB-immunodepleted HeLa cell nuclear extract (NE). Mutations in conserved
      residues located on the sides of the B-finger had the greatest effect on activity
      in both minimal promoter systems, with mutations in residues Glu-51 and Arg-66
      eliminating activity. The double change-of-charge mutant (E51R:R66E) did not show
      activity in either minimal promoter system. Mutations in the nonconserved
      residues at the tip of the B-finger did not significantly affect activity.
      However, all of the mutations in the B-finger showed at least 25% activity in the
      HeLa cell NE. Chimeric proteins, containing B-finger sequences from species with
      conserved residues on the side of the B-finger, showed wild-type activity in a
      minimal promoter system and in the HeLa cell NE. However, chimeric proteins whose
      sequence showed divergence on the sides of the B-finger had reduced activity.
      Transcription factor IIF (TFIIF) partially restored activity of the inactive
      mutants in the minimal promoter system, suggesting that TFIIF in HeLa cell NE
      helps to rescue the inactive mutations by interacting with either the B-finger or
      another component of the initiation complex that is influenced by the B-finger.

PMID- 19590099
TI  - Case study on visualizing hurricanes using illustration-inspired techniques.
AB  - The devastating power of hurricanes was evident during the 2005 hurricane season,
      the most active season on record. This has prompted increased efforts by
      researchers to understand the physical processes that underlie the genesis,
      intensification, and tracks of hurricanes. This research aims at facilitating an
      improved understanding into the structure of hurricanes with the aid of
      visualization techniques. Our approach was developed by a mixed team of
      visualization and domain experts. To better understand these systems, and to
      explore their representation in NWP models, we use a variety of illustration
      inspired techniques to visualize their structure and time evolution. Illustration
      inspired techniques aid in the identification of the amount of vertical wind
      shear in a hurricane, which can help meteorologists predict dissipation.
      Illustration-style visualization, in combination with standard visualization
      techniques, helped explore the vortex rollup phenomena and the mesovortices
      contained within. We evaluated the effectiveness of our visualization with the
      help of six hurricane experts. The expert evaluation showed that the illustration
      inspired techniques were preferred over existing tools. Visualization of the
      evolution of structural features is a prelude to a deeper visual analysis of the
      underlying dynamics.

PMID- 19590100
TI  - Planetary-scale terrain composition.
AB  - Many interrelated planetary height map and surface image map data sets exist, and
      more data are collected each day. Broad communities of scientists require tools
      to compose these data interactively and explore them via real-time visualization.
      While related, these data sets are often unregistered with one another, having
      different projection, resolution, format, and type. We present a GPU-centric
      approach to the real-time composition and display of unregistered-but-related
      planetary-scale data. This approach employs a GPGPU process to tessellate
      spherical height fields. It uses a render-to-vertex-buffer technique to operate
      upon polygonal surface meshes in image space, allowing geometry processes to be
      expressed in terms of image processing. With height and surface map data
      processing unified in this fashion, a number of powerful composition operations
      may be uniformly applied to both. Examples include adaptation to nonuniform
      sampling due to projection, seamless blending of data of disparate resolution or
      transformation regardless of boundary, and the smooth interpolation of levels of
      detail in both geometry and imagery. Issues of scalability and precision are
      addressed, giving out-of-core access to giga-pixel data sources, and correct
      rendering at scales approaching one meter.

PMID- 19590096
TI  - Structural, functional, and bioinformatic studies demonstrate the crucial role of
      an extended peptide binding site for the SH3 domain of yeast Abp1p.
AB  - SH3 domains, which are among the most frequently occurring protein interaction
      modules in nature, bind to peptide targets ranging in length from 7 to more than
      25 residues. Although the bulk of studies on the peptide binding properties of
      SH3 domains have focused on interactions with relatively short peptides (less
      than 10 residues), a number of domains have been recently shown to require much
      longer sequences for optimal binding affinity. To gain greater insight into the
      binding mechanism and biological importance of interactions between an SH3 domain
      and extended peptide sequences, we have investigated interactions of the yeast
      Abp1p SH3 domain (AbpSH3) with several physiologically relevant 17-residue target
      peptide sequences. To obtain a molecular model for AbpSH3 interactions, we solved
      the structure of the AbpSH3 bound to a target peptide from the yeast actin patch
      kinase, Ark1p. Peptide target complexes from binding partners Scp1p and Sjl2p
      were also characterized, revealing that the AbpSH3 uses a common extended
      interface for interaction with these peptides, despite K(d) values for these
      peptides ranging from 0.3 to 6 mum. Mutagenesis studies demonstrated that
      residues across the whole 17-residue binding site are important both for maximal
      in vitro binding affinity and for in vivo function. Sequence conservation
      analysis revealed that both the AbpSH3 and its extended target sequences are
      highly conserved across diverse fungal species as well as higher eukaryotes. Our
      data imply that the AbpSH3 must bind extended target sites to function
      efficiently inside the cell.

PMID- 19590101
TI  - Distribution-driven visualization of volume data.
AB  - Feature detection and display are the essential goals of the visualization
      process. Most visualization software achieves these goals by mapping properties
      of sampled intensity values and their derivatives to color and opacity. In this
      work, we propose to explicitly study the local frequency distribution of
      intensity values in broader neighborhoods centered around each voxel. We have
      found frequency distributions to contain meaningful and quantitative information
      that is relevant for many kinds of feature queries. Our approach allows users to
      enter predicate-based hypotheses about relational patterns in local distributions
      and render visualizations that show how neighborhoods match the predicates.
      Distributions are a familiar concept to nonexpert users, and we have built a
      simple graphical user interface for forming and testing queries interactively.
      The query framework readily applies to arbitrary spatial data sets and supports
      queries on time variant and multifield data. Users can directly query for classes
      of features previously inaccessible in general feature detection tools. Using
      several well-known data sets, we show new quantitative features that enhance our
      understanding of familiar visualization results.

PMID- 19590103
TI  - A survey of radial methods for information visualization.
AB  - Radial visualization, or the practice of displaying data in a circular or
      elliptical pattern, is an increasingly common technique in information
      visualization research. In spite of its prevalence, little work has been done to
      study this visualization paradigm as a methodology in its own right. We provide a
      historical review of radial visualization, tracing it to its roots in centuries
      old statistical graphics. We then identify the types of problem domains to which
      modern radial visualization techniques have been applied. A taxonomy for radial
      visualization is proposed in the form of seven design patterns encompassing
      nearly all recent works in this area. From an analysis of these patterns, we
      distill a series of design considerations that system builders can use to create
      new visualizations that address aspects of the design space that have not yet
      been explored. It is hoped that our taxonomy will provide a framework for
      facilitating discourse among researchers and stimulate the development of
      additional theories and systems involving radial visualization as a distinct
      design metaphor.

PMID- 19590104
TI  - Uncluttering graph layouts using anisotropic diffusion and mass transport.
AB  - Many graph layouts include very dense areas, making the layout difficult to
      understand. In this paper, we propose a technique for modifying an existing
      layout in order to reduce the clutter in dense areas. A physically inspired
      evolution process based on a modified heat equation is used to create an improved
      layout density image, making better use of available screen space. Using results
      from optimal mass transport problems, a warp to the improved density image is
      computed. The graph nodes are displaced according to the warp. The warp maintains
      the overall structure of the graph, thus limiting disturbances to the mental map,
      while reducing the clutter in dense areas of the layout. The complexity of the
      algorithm depends mainly on the resolution of the image visualizing the graph and
      is linear in the size of the graph. This allows scaling the computation according
      to required running times. It is demonstrated how the algorithm can be
      significantly accelerated using a graphics processing unit (GPU), resulting in
      the ability to handle large graphs in a matter of seconds. Results on several
      layout algorithms and applications are demonstrated.

PMID- 19590102
TI  - Enhancing realism of wet surfaces in temporal bone surgical simulation.
AB  - We present techniques to improve visual realism in an interactive surgical
      simulation application: a mastoidectomy simulator that offers a training
      environment for medical residents as a complement to using a cadaver. As well as
      displaying the mastoid bone through volume rendering, the simulation allows users
      to experience haptic feedback and appropriate sound cues while controlling a
      virtual bone drill and suction/irrigation device. The techniques employed to
      improve realism consist of a fluid simulator and a shading model. The former
      allows for deformable boundaries based on volumetric bone data, while the latter
      gives a wet look to the rendered bone to emulate more closely the appearance of
      the bone in a surgical environment. The fluid rendering includes bleeding
      effects, meniscus rendering, and refraction. We incorporate a planar
      computational fluid dynamics simulation into our three-dimensional rendering to
      effect realistic blood diffusion. Maintaining real-time performance while
      drilling away bone in the simulation is critical for engagement with the system.

PMID- 19590105
TI  - Efficient and accurate sound propagation using adaptive rectangular
      decomposition.
AB  - Accurate sound rendering can add significant realism to complement visual display
      in interactive applications, as well as facilitate acoustic predictions for many
      engineering applications, like accurate acoustic analysis for architectural
      design. Numerical simulation can provide this realism most naturally by modeling
      the underlying physics of wave propagation. However, wave simulation has
      traditionally posed a tough computational challenge. In this paper, we present a
      technique which relies on an adaptive rectangular decomposition of 3D scenes to
      enable efficient and accurate simulation of sound propagation in complex virtual
      environments. It exploits the known analytical solution of the Wave Equation in
      rectangular domains, and utilizes an efficient implementation of the Discrete
      Cosine Transform on Graphics Processors (GPU) to achieve at least a 100-fold
      performance gain compared to a standard Finite-Difference Time-Domain (FDTD)
      implementation with comparable accuracy, while also being 10-fold more memory
      efficient. Consequently, we are able to perform accurate numerical acoustic
      simulation on large, complex scenes in the kilohertz range. To the best of our
      knowledge, it was not previously possible to perform such simulations on a
      desktop computer. Our work thus enables acoustic analysis on large scenes and
      auditory display for complex virtual environments on commodity hardware.

PMID- 19590106
TI  - Efficient LBM visual simulation on face-centered cubic lattices.
AB  - The Lattice Boltzmann method (LBM) for visual simulation of fluid flow generally
      employs cubic Cartesian (CC) lattices such as the D3Q13 and D3Q19 lattices for
      the particle transport. However, the CC lattices lead to suboptimal
      representation of the simulation space. We introduce the face-centered cubic
      (FCC) lattice, fD3Q13, for LBM simulations. Compared to the CC lattices, the
      fD3Q13 lattice creates a more isotropic sampling of the simulation domain and its
      single lattice speed (i.e., link length) simplifies the computations and data
      storage. Furthermore, the fD3Q13 lattice can be decomposed into two independent
      interleaved lattices, one of which can be discarded, which doubles the simulation
      speed. The resulting LBM simulation can be efficiently mapped to the GPU, further
      increasing the computational performance. We show the numerical advantages of the
      FCC lattice on channeled flow in 2D and the flow-past-a-sphere benchmark in 3D.
      In both cases, the comparison is against the corresponding CC lattices using the
      analytical solutions for the systems as well as velocity field visualizations. We
      also demonstrate the performance advantages of the fD3Q13 lattice for interactive
      simulation and rendering of hot smoke in an urban environment using thermal LBM.

PMID- 19590107
TI  - Image-based modeling of the human eye.
AB  - Rendering realistic organic materials is a challenging issue. The human eye is an
      important part of nonverbal communication which, consequently, requires specific
      modeling and rendering techniques to enhance the realism of virtual characters.
      We propose an image-based method for estimating both iris morphology and
      scattering features in order to generate convincing images of virtual eyes. In
      this regard, we develop a technique to unrefract iris photographs. We model the
      morphology of the human iris as an irregular multilayered tissue. We then
      approximate the scattering features of the captured iris. Finally, we propose a
      real-time rendering technique based on the subsurface texture mapping
      representation and introduce a precomputed refraction function as well as a
      caustic function, which accounts for the light interactions at the corneal
      interface.

PMID- 19590108
TI  - Refilming with depth-inferred videos.
AB  - Compared to still image editing, content-based video editing faces the additional
      challenges of maintaining the spatiotemporal consistency with respect to
      geometry. This brings up difficulties of seamlessly modifying video content, for
      instance, inserting or removing an object. In this paper, we present a new video
      editing system for creating spatiotemporally consistent and visually appealing
      refilming effects. Unlike the typical filming practice, our system requires no
      labor-intensive construction of 3D models/surfaces mimicking the real scene.
      Instead, it is based on an unsupervised inference of view-dependent depth maps
      for all video frames. We provide interactive tools requiring only a small amount
      of user input to perform elementary video content editing, such as separating
      video layers, completing background scene, and extracting moving objects. These
      tools can be utilized to produce a variety of visual effects in our system,
      including but not limited to video composition, "predator" effect, bullet-time,
      depth-of-field, and fog synthesis. Some of the effects can be achieved in real
      time.

PMID- 19590109
TI  - TransCAIP: A Live 3D TV system using a camera array and an integral photography
      display with interactive control of viewing parameters.
AB  - The system described in this paper provides a real-time 3D visual experience by
      using an array of 64 video cameras and an integral photography display with 60
      viewing directions. The live 3D scene in front of the camera array is reproduced
      by the full-color, full-parallax autostereoscopic display with interactive
      control of viewing parameters. The main technical challenge is fast and flexible
      conversion of the data from the 64 multicamera images to the integral photography
      format. Based on image-based rendering techniques, our conversion method first
      renders 60 novel images corresponding to the viewing directions of the display,
      and then arranges the rendered pixels to produce an integral photography image.
      For real-time processing on a single PC, all the conversion processes are
      implemented on a GPU with GPGPU techniques. The conversion method also allows a
      user to interactively control viewing parameters of the displayed image for
      reproducing the dynamic 3D scene with desirable parameters. This control is
      performed as a software process, without reconfiguring the hardware system, by
      changing the rendering parameters such as the convergence point of the rendering
      cameras and the interval between the viewpoints of the rendering cameras.

PMID- 19590110
TI  - Multiresolution mean shift clustering algorithm for shape interpolation.
AB  - In this paper, we solve the problem of 3D shape interpolation with significant
      pose variation. For an ideal 3D shape interpolation, especially the articulated
      model, the shape should follow the movement of the underlying articulated
      structure and be transformed in a way that is as rigid as possible. Given input
      shapes with compatible connectivity, we propose a novel multiresolution mean
      shift (MMS) clustering algorithm to automatically extract their near-rigid
      components. Then, by building the hierarchical relationship among extracted
      components, we compute a common articulated structure for these input shapes.
      With the aid of this articulated structure, we solve the shape interpolation by
      combining 1) a global pose interpolation of near-rigid components from the source
      shape to the target shape with 2) a local gradient field interpolation for each
      pair of components, followed by solving a Poisson equation in order to
      reconstruct an interpolated shape. As a result, an aesthetically pleasing shape
      interpolation can be generated, with even the poses of shapes varying
      significantly. In contrast to a recent state-of-the-art work, the proposed
      approach can achieve comparable or even better results and have better
      computational efficiency as well.

PMID- 19590111
TI  - Compatible embedding for 2D shape animation.
AB  - We present new algorithms for the compatible embedding of 2D shapes. Such
      embeddings offer a convenient way to interpolate shapes having complex, detailed
      features. Compared to existing techniques, our approach requires less user input,
      and is faster, more robust, and simpler to implement, making it ideal for
      interactive use in practical applications. Our new approach consists of three
      parts. First, our boundary matching algorithm locates salient features using the
      perceptually motivated principles of scale-space and uses these as automatic
      correspondences to guide an elastic curve matching algorithm. Second, we simplify
      boundaries while maintaining their parametric correspondence and the embedding of
      the original shapes. Finally, we extend the mapping to shapes' interiors via a
      new compatible triangulation algorithm. The combination of our algorithms allows
      us to demonstrate 2D shape interpolation with instant feedback. The proposed
      algorithms exhibit a combination of simplicity, speed, and accuracy that has not
      been achieved in previous work.

PMID- 19590112
TI  - Ventricular rhythm in atrial fibrillation under anaesthetic infusion with
      propofol.
AB  - Changes in patients' autonomic tone and specific pharmacologic interventions may
      modify the ventricular response (actual heart rate) during atrial fibrillation
      (AF). Hypnotic agents such as propofol may modify autonomic balance as they
      promote a sedative state. It has been shown that propofol slightly slows atrial
      fibrillatory activity, but the net global effect on the ventricular response
      remains unknown. We aimed to evaluate in patients in AF the effect of a propofol
      bolus on the ventricular rate and regularity at ECG. We analysed the possible
      relation with local atrial fibrillatory activities, as ratios between atrial and
      ventricular rates (AVRs), analysing atrial activity from intracardiac
      electrograms at the free wall of the right and left atria and at the interatrial
      septum. We compared data at the baseline and after complete hypnosis. Propofol
      was associated with a more homogeneous ventricular response and lower AVR values
      at the interatrial septum.

PMID- 19590113
TI  - Heart rate variability during sleep in healthy term newborns in the early
      postnatal period.
AB  - Normative time- and frequency-domain heart rate variability (HRV) measures were
      extracted during quiet sleep (QS) and active sleep (AS) periods in 30 healthy
      babies. All newborn infants studied were less than 12 h old and the sleep state
      was classified using multi-channel video EEG. Three bands were extracted from the
      heart rate (HR) spectrum: very low frequency (VLF), 0.01-0.04 Hz; low frequency
      (LF), 0.04-0.2 Hz, and high frequency (HF), >0.2 Hz. All metrics were averaged
      across all patients and per sleep state to produce a table of normative values. A
      noticeable peak corresponding to activity in the RSA band was found in 80%
      patients during QS and 0% of patients during AS, although some broadband activity
      was observed. The majority of HRV metrics showed a statistically significant
      separation between QS and AS. It can be concluded that (i) activity in the RSA
      band is present during QS in the healthy newborn, in the first 12 h of life, (ii)
      HRV measures are affected by sleep state and (iii) the averaged HRV metrics
      reported here could assist the interpretation of HRV data from newborns with
      neonatal illnesses.

PMID- 19590114
TI  - Simulation of dose deposition in stereotactic synchrotron radiation therapy: a
      fast approach combining Monte Carlo and deterministic algorithms.
AB  - A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is
      proposed to compute the distribution of dose deposited during stereotactic
      synchrotron radiation therapy treatment. The proposed approach divides the
      computation into two parts: (i) the dose deposited by primary radiation (coming
      directly from the incident x-ray beam) is calculated in a deterministic way using
      ray casting techniques and energy-absorption coefficient tables and (ii) the dose
      deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence)
      is computed using a hybrid algorithm combining MC and deterministic calculations.
      In the MC part, a small number of particle histories are simulated. Every time a
      scattering or fluorescence event takes place, a splitting mechanism is applied,
      so that multiple secondary photons are generated with a reduced weight. The
      secondary events are further processed in a deterministic way, using ray casting
      techniques. The whole simulation, carried out within the framework of the Monte
      Carlo code Geant4, is shown to converge towards the same results as the full MC
      simulation. The speed of convergence is found to depend notably on the splitting
      multiplicity, which can easily be optimized. To assess the performance of the
      proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated
      by the track length estimator technique (TLE), considering a clinically realistic
      test case. It is found that the hybrid approach is significantly faster than the
      MC/TLE method. The gain in speed in a test case was about 25 for a constant
      precision. Therefore, this method appears to be suitable for treatment planning
      applications.

PMID- 19590115
TI  - An examination of automatic exposure control regimes for two digital radiography
      systems.
AB  - The influence of two methods of an automatic exposure control (AEC) setup using a
      simple measure of detectability is examined as a function of x-ray beam quality
      for a computed radiography (CR) system and for an indirect conversion digital
      radiography (DR) system. The regimes assessed were constant air kerma at the
      detector and the constant contrast noise ratio (CNR). A low scatter geometry was
      employed with x-ray spectra varying from 60 kV and 1 mm Cu to 125 kV and 2 mm Cu.
      The CNR was measured using a 2 mm thick Al square of dimension 1 cm by 1 cm.
      Detectability was quantified via a nominal contrast for a fixed beam quality of
      70 kV and 1 mm added Cu filtration, taken from c-d curves measured using the
      Leeds TO20 test object, for the four x-ray spectra. In addition, objective image
      quality parameters including modulation transfer function (MTF), noise power
      spectrum (NPS) and detective quantum efficiency (DQE) were also measured for both
      systems at the four different x-ray spectra. It was found that the constant air
      kerma strategy did not maintain threshold nominal contrast (simple detectability)
      constant as the x-ray beam mean energy increased, for either the CR system or the
      DR system. For the CR detector, the threshold nominal contrast for a 1 mm disc
      increased by a factor of 4.4 from 3.50% to 15.4% as the tube potential was raised
      from 60 kV to 125 kV, while for the DR detector, the threshold nominal contrast
      increased by a factor of 3.4, from 2.27% to 7.67% as the tube potential increased
      from 60 kV to 120 kV. The constant CNR method was more successful at maintaining
      constant detectability for the c-d discs. The threshold nominal contrast for the
      1 mm disc changed by a factor of 1.2, from 4.80% to 5.70% for the CR system, as
      the spectrum changed from 60 kV to 125 kV. For the indirect conversion detector,
      the threshold nominal contrast increased from 2.27% to 5.66% (a factor of 1.4
      increase). The constant CNR strategy required an increase in air kerma by factors
      of 14.5 and 4.5 for the CR and DR detectors, respectively. The Rose SNR was used
      to show that the air kerma at the detector should be modulated by the inverse of
      the measured contrast loss squared and by the inverse of the reduction in the low
      frequency DQE of the detector, in order to maintain the Rose SNR constant.
      Calculations of air kerma required for a constant Rose SNR, made using the
      measured contrast and the extrapolated DQE(0), were within 25% of the air kerma
      for the measured CNR method for both detectors. These results suggest that the
      constant CNR strategy keeps simple object detectability constant by increasing
      air kerma to overcome (a) the contrast loss and (b) the photon loss, due to a
      reduction in DQE as the mean energy is increased. AEC systems set up to hold air
      kerma constant or nearly constant at the x-ray detector will not maintain a
      constant level of contrast-detail detectability as x-ray energy changes. The
      constant CNR method is considerably more successful if fixed contrast-detail
      detectability is required for different x-ray beam qualities.

PMID- 19590116
TI  - Cone beam computerized tomography: the effect of calibration of the Hounsfield
      unit number to electron density on dose calculation accuracy for adaptive
      radiation therapy.
AB  - The availability of cone beam computerized tomography (CBCT) images at the time
      of treatment has opened possibilities for dose calculations representing the
      delivered dose for adaptive radiation therapy. A significant component in the
      accuracy of dose calculation is the calibration of the Hounsfield unit (HU)
      number to electron density (ED). The aim of this work is to assess the impact of
      HU to ED calibration phantom insert composition and phantom volume on dose
      calculation accuracy for CBCT. CBCT HU to ED calibration curves for different
      commercial phantoms were measured and compared. The effect of the scattering
      volume of the phantom on the HU to ED calibration was examined as a function of
      phantom length and radial diameter. The resulting calibration curves were used at
      the treatment planning system to calculate doses for geometrically simple
      phantoms and a pelvic anatomical phantom to compare against measured doses. Three
      dimensional dose distributions for the pelvis phantom were calculated using the
      HU to ED curves and compared using Chi comparisons. The HU to ED calibration
      curves for the commercial phantoms diverge at densities greater than that of
      water, depending on the elemental composition of the phantom insert. The effect
      of adding scatter material longitudinally, increasing the phantom length from 5
      cm to 26 cm, was found to be up to 260 HU numbers for the high-density insert.
      The change in the HU value, by increasing the diameter of the phantom from 18 to
      40 cm, was found to be up to 1200 HU for the high-density insert. The effect of
      phantom diameter on the HU to ED curve can lead to dose differences for 6 MV and
      18 MV x-rays under bone inhomogeneities of up to 20% in extreme cases. These
      results show significant dosimetric differences when using a calibration phantom
      with materials which are not tissue equivalent. More importantly, the amount of
      scattering material used with the HU to ED calibration phantom has a significant
      effect on the dosimetric accuracy, particularly in the radial direction.

PMID- 19590117
TI  - Deconvolution of x-ray phase contrast images as a way to retrieve phase
      information lost due to insufficient resolution.
AB  - When free-space propagation x-ray phase contrast imaging is implemented outside
      synchrotron radiation facilities, the combined effect of detector resolution and
      source size swamps the fine phase contrast fringes, often making them almost
      undetectable. In an attempt to mitigate this effect, a simple deconvolution
      procedure based on division in the Fourier space plus multiplication by an
      appropriate filter was applied to experimental x-ray phase contrast images of a
      simple geometric phantom. The filter parameter was varied in order to assess its
      impact on the level of retrieved phase signal. The deconvolved images were
      compared to simulated ones obtained under different resolution conditions,
      showing that this simple procedure provided signals equivalent to those that
      would be obtained with a detector with three times better resolution. By
      accepting an increase in the overall image noise, the method also appears to
      bring up secondary phase contrast fringes, which are not visible in the
      unprocessed signal.

PMID- 19590119
TI  - Fragmentation and plasmid strand breaks in pure and gold-doped DNA irradiated by
      beams of fast hydrogen atoms.
AB  - The results of an investigation into the damage caused to dry plasmid DNA after
      irradiation by fast (keV) hydrogen atoms are presented. Agarose gel
      electrophoresis was used to assess single and double strand break yields as a
      function of dose in dry DNA samples deposited on a mica substrate. Damage levels
      were observed to increase with beam energy. Strand break yields demonstrated a
      considerable dependence on sample structure and the method of sample preparation.
      Additionally, the effect of high-Z nanoparticles on damage levels was
      investigated by irradiating DNA samples containing controlled amounts of gold
      nanoparticles. In contrast to previous (photonic) studies, no enhancement of
      strand break yields was observed with the particles showing a slight
      radioprotective effect. A model of DNA damage as a function of dose has been
      constructed in terms of the probability for the creation of single and double
      strand breaks, per unit ion flux. This model provides quantitative conclusions
      about the effects of both gold nanoparticles and the different buffers used in
      performing the assays and, in addition, infers the proportion of multiply damaged
      fragments.

PMID- 19590121
TI  - Comparing probabilistic microbial risk assessments for drinking water against
      daily rather than annualised infection probability targets.
AB  - Some national drinking water guidelines provide guidance on how to define 'safe'
      drinking water. Regarding microbial water quality, a common position is that the
      chance of an individual becoming infected by some reference waterborne pathogen
      (e.g. Cryptsporidium) present in the drinking water should < 10(-4) in any year.
      However the instantaneous levels of risk to a water consumer vary over the course
      of a year, and waterborne disease outbreaks have been associated with shorter
      duration periods of heightened risk. Performing probabilistic microbial risk
      assessments is becoming commonplace to capture the impacts of temporal
      variability on overall infection risk levels. A case is presented here for
      adoption of a shorter-duration reference period (i.e. daily) infection
      probability target over which to assess, report and benchmark such risks. A daily
      infection probability benchmark may provide added incentive and guidance for
      exercising control over short-term adverse risk fluctuation events and their
      causes. Management planning could involve outlining measures so that the daily
      target is met under a variety of pre-identified event scenarios. Other benefits
      of a daily target could include providing a platform for managers to design and
      assess management initiatives, as well as simplifying the technical components of
      the risk assessment process.

PMID- 19590120
TI  - Accurate helical cone-beam CT reconstruction with redundant data.
AB  - We present a new image reconstruction algorithm for helical cone-beam computed
      tomography (CT). This algorithm is designed for data collected at or near maximum
      pitch, and provides a theoretically exact and stable reconstruction while
      beneficially using all measured data. The main operations involved are a
      differentiated backprojection and a finite-support Hilbert transform inversion.
      These operations are applied onto M-lines, and the beneficial use of all measured
      data is gained from averaging three volumes reconstructed each with a different
      choice of M-lines. The technique is overall similar to that presented by one of
      the authors in a previous publication, but operates volume-wise, instead of voxel
      wise, which yields a significantly more efficient reconstruction procedure. The
      algorithm is presented in detail. Also, preliminary results from computer
      simulated data are provided to demonstrate the numerical stability of the
      algorithm, the beneficial use of redundant data and the ability to process data
      collected with an angular flying focal spot.

PMID- 19590122
TI  - Optimising water treatment practices for the removal of Anabaena circinalis and
      its associated metabolites, geosmin and saxitoxins.
AB  - The cyanobacterium Anabaena circinalis has the ability to co-produce geosmin and
      saxitoxins, compounds which can compromise the quality of drinking water. This
      study provides pertinent information in optimising water treatment practices for
      the removal of geosmin and saxitoxins. In particular, it demonstrates that pre
      oxidation using potassium permanganate could be applied at the head of water
      treatment plants without releasing intracellular geosmin and saxitoxins from A.
      circinalis. Furthermore, powdered activated carbon (PAC) was shown to be an
      effective treatment barrier for the removal of extracellular (dissolved) geosmin
      and saxitoxins, with similar adsorption trends of both compounds. The relative
      removal of the saxitoxins compared with geosmin was determined to be 0.84 +/-
      0.27, which implies that saxitoxin removal with PAC can be estimated to be
      approximately 60 to 100% of the removal of geosmin under equivalent conditions.
      Chlorine was shown to be effective for the oxidation of the saxitoxins with CT
      values of approximately 30 mg min l(-1) required for greater than 90% destruction
      of the saxitoxins.

PMID- 19590118
TI  - Excitation spectroscopy in multispectral optical fluorescence tomography:
      methodology, feasibility and computer simulation studies.
AB  - Molecular probes used for in vivo optical fluorescence tomography (OFT) studies
      in small animals are typically chosen such that their emission spectra lie in the
      680-850 nm wavelength range. This is because tissue attenuation in this spectral
      band is relatively low, allowing optical photons even from deep sites in tissue
      to reach the animal surface and consequently be detected by a CCD camera. The
      wavelength dependence of tissue optical properties within the 680-850 nm band can
      be exploited for emitted light by measuring fluorescent data via multispectral
      approaches and incorporating the spectral dependence of these optical properties
      into the OFT inverse problem-that of reconstructing underlying 3D fluorescent
      probe distributions from optical data collected on the animal surface. However,
      in the aforementioned spectral band, due to only small variations in the tissue
      optical properties, multispectral emission data, though superior for image
      reconstruction compared to achromatic data, tend to be somewhat redundant. A
      different spectral approach for OFT is to capitalize on the larger variations in
      the optical properties of tissue for excitation photons than for the emission
      photons by using excitation at multiple wavelengths as a means of decoding source
      depth in tissue. The full potential of spectral approaches in OFT can be realized
      by a synergistic combination of these two approaches, that is, exciting the
      underlying fluorescent probe at multiple wavelengths and measuring emission data
      multispectrally. In this paper, we describe a method that incorporates both
      excitation and emission spectral information into the OFT inverse problem. We
      describe a linear algebraic formulation of the multiple wavelength illumination
      multispectral detection forward model for OFT and compare it to models that use
      only excitation at multiple wavelengths or those that use only multispectral
      detection techniques. This study is carried out in a realistic inhomogeneous
      mouse atlas using singular value decomposition and analysis of reconstructed
      spatial resolution versus noise. For simplicity, quantitative results have been
      shown for one representative fluorescent probe (Alexa 700) and effects due to
      tissue autofluorescence have not been taken into account. We also demonstrate the
      performance of our method for 3D reconstruction of tumors in a simulated mouse
      model of metastatic human hepatocellular carcinoma.

PMID- 19590124
TI  - Is there still a problem with lead in drinking water in the European Union?
AB  - The presence of lead in drinking water poses a range of risks to human health,
      including the retardation of some aspects of child development, the inducement of
      abortion, and other clinical disorders. The extent of these risks has not been
      quantified at the European Union (EU) scale. A number of sampling methods are in
      use across the EU, some of which are inadequate for determining the
      concentrations of lead in drinking water at consumers' taps. In consequence, non
      compliance with the EU standards for lead in drinking water has been under
      estimated. Emerging data indicates significant non-compliance with these
      standards in some countries, particularly with the 10 microg(-1) standard that
      will become a legal requirement in 2013; the current interim standard of 25
      microg l(-1) is also exceeded in some locations. An initial estimate is that 25%
      of domestic dwellings in the EU have a lead pipe, either as a connection to the
      water main, or as part of the internal plumbing, or both, potentially putting 120
      million people at risk from lead in drinking water within the EU. These issues
      are relevant to the implementation of the Protocol on Water and Health and to
      drinking water safety planning.

PMID- 19590123
TI  - Quantifying the burden of disease associated with inadequate provision of water
      and sanitation in selected sub-Saharan refugee camps.
AB  - A WHO methodology is used for the first time to estimate the burden of disease
      directly associated with incomplete water and sanitation provision in refugee
      camps in sub-Saharan African countries. In refugee camps of seven countries,
      containing just fewer than 1 million people in 2005, there were 132,000 cases of
      diarrhoea and over 280,000 reported cases of malaria attributable to incomplete
      water and sanitation provision. In the period from 2005 to 2007 1,400 deaths were
      estimated to be directly attributable to incomplete water and sanitation alone in
      refugee camps in Ethiopia, Kenya and Tanzania. A comparison with national
      morbidity estimates from WHO shows that although diarrhoea estimates in the camps
      are often higher, mortality estimates are generally much lower, which may reflect
      on more ready access to medical aid within refugee camps. Despite the many
      limitations, these estimates highlight the burden of disease connected to
      incomplete water and sanitation provision in refugee settings and can assist
      resource managers to identify camps requiring specific interventions.
      Additionally the results reinforce the importance of increasing dialogue between
      the water, sanitation and health sectors and underline the fact that efforts to
      reduce refugee morbidity would be greatly enhanced by strengthening water and
      sanitation provision.

PMID- 19590125
TI  - Enteric illness risks before and after water treatment improvements.
AB  - This study evaluated whether occurrence of acute gastrointestinal illnesses
      declined after filtration and ozonation were added to a previously unfiltered,
      chlorinated high-quality surface water source in a northwest United States city.
      Enteric and other illnesses were recorded for two 6-month periods for control and
      intervention sites in the same city. During phase 1, chlorinated, unfiltered
      drinking water for both sites was obtained from protected watersheds. During
      phase 2, the intervention site received chlorinated, filtered and ozonated
      drinking water. The water was not altered in the control site. No overall
      differences were found in the risk of any of the illnesses after the new water
      treatment plant was completed. There was a significantly increased risk of
      diarrhoea and highly credible gastrointestinal illness in participants with three
      or more episodes of the same type of illness during phase 1.

PMID- 19590126
TI  - Hygienic effects and gas production of plastic bio-digesters under tropical
      conditions.
AB  - Plastic plug-flow bio-digesters have been promoted as a good option for improved
      treatment of manure and wastewater in developing countries although minimal
      information has been published on their hygienic status. This bench-scale study
      replicates bio-digester conditions to evaluate the reduction of pathogen and
      indicator microorganisms at three different hydraulic retention times (HRT) in
      the anaerobic treatment of pig manures at 30 degrees C for 50 days. Results
      showed that physicochemical values differed between HRTs. Gas production
      efficiency was better for longer HRTS. The accumulated sludge at the reactor's
      base increased with longer HRT. Phages and bacteria examined were reduced, but
      none was completely eliminated. Log10 reduction of bacteria ranged from 0.54 to
      2.47. Phages ranged from 1.60 to 3.42. The reduction of organisms at HRT = 30
      days was about one log10 unit higher than HRT = 15 days and about two log10 units
      higher than HRT = 3 days. The results indicate that the reduction of tested
      organisms increases with HRT. However the hygienic quality of the liquid effluent
      does not meet required quality values for surface and irrigation water. Longer
      HRTs are recommended to increase gas yield and achieve higher pathogen reduction.
      More barriers should be applied while handling bio-digester outputs to minimise
      risks to environmental and human health.

PMID- 19590127
TI  - Decline in recycled water quality during short-term storage in open ponds.
AB  - Changes were assessed in urban wastewater treatment plant (WWTP) effluent quality
      during short-term storage in open surface ponds. Water quality was monitored over
      five years at the inlets and outlets of open storage ponds located at three
      biological nutrient removal plants. Pond influent temperature, rainfall and
      sewage inflow were not found to be major factors. However, there was a trend for
      water temperature to be correlated negatively with nitrogenous nutrient and
      positively with faecal coliform values. The observed increases in faecal
      coliforms, nutrients and chemical oxygen demand were most likely caused through
      avian faecal contamination. These increases challenge the notion that pond
      storage has a positive or negligible effect on effluent quality. The observed one
      to two orders of magnitude increase in faecal coliforms may affect reuse scheme
      viability by limiting the range of uses under Australian water recycling
      guidelines. Potential improvements to short-term recycled water storage
      management at WWTPs could include the integration of monitoring requirements in
      WWTP discharge licences and recycling guidelines and the monitoring of all water
      quality parameters, including microbiological ones, at the point of entry into
      the recycled water distribution system, after WWTP storage, rather than directly
      post-disinfection.

PMID- 19590128
TI  - Data gaps in evidence-based research on small water enterprises in developing
      countries.
AB  - Small water enterprises (SWEs) are water delivery operations that predominantly
      provide water at the community level. SWEs operate beyond the reach of piped
      water systems, selling water to households throughout the world. Their ubiquity
      in the developing world and access to vulnerable populations suggests that these
      small-scale water vendors may prove valuable in improving potable water
      availability. This paper assesses the current literature on SWEs to evaluate
      previous studies and determine gaps in the evidence base. Piped systems and point
      of-use products were not included in this assessment. Results indicate that SWES
      are active in urban, peri-urban and rural areas of Africa, Asia and Latin
      America. Benefits of SWEs include: no upfront connection fees; demand-driven and
      flexible to local conditions; and service to large populations without high costs
      of utility infrastructure. Disadvantages of SWEs include: higher charges for
      water per unit of volume compared with infrastructure-based utilities; lack of
      regulation; operation often outside legal structures; no water quality
      monitoring; increased potential for conflict with local utilities; and potential
      for extortion by local officials. No rigorous, evidence-based, peer-reviewed
      scientific studies that control for confounders examining the effectiveness of
      SWEs in providing potable water were identified.

PMID- 19590129
TI  - Hand-mouth transfer and potential for exposure to E. coli and F+ coliphage in
      beach sand, Chicago, Illinois.
AB  - Beach sand contains fecal indicator bacteria, often in densities greatly
      exceeding the adjacent swimming waters. We examined the transferability of
      Escherichia coli and F+ coliphage (MS2) from beach sand to hands in order to
      estimate the potential subsequent health risk. Sand with high initial E. coli
      concentrations was collected from a Chicago beach. Individuals manipulated the
      sand for 60 seconds, and rinse water was analysed for E. coli and coliphage. E.
      coli densities transferred were correlated with density in sand rather than
      surface area of an individual's hand, and the amount of coliphage transferred
      from seeded sand was different among individuals. In sequential rinsing,
      percentage reduction was 92% for E. coli and 98% for coliphage. Using dose
      response estimates developed for swimming water, it was determined that the
      number of individuals per thousand that would develop gastrointestinal symptoms
      would be 11 if all E. coli on the fingertip were ingested or 33 if all E. coli on
      the hand were ingested. These results suggest that beach sand may be an important
      medium for microbial exposure; bacteria transfer is related to initial
      concentration in the sand; and rinsing may be effective in limiting oral exposure
      to sand-borne microbes of human concern.

PMID- 19590130
TI  - The case for re-evaluating the upper limit value for selenium in drinking water
      in Europe.
AB  - Selenium is an essential trace element for life, which can be toxic for humans
      when intakes reach a certain amount. Therefore, since the margin between healthy
      intake and toxic intake is narrow, the selenium concentration of tap water is a
      parameter that must be monitored because of its potential for increased intake.
      The present work gives an overview of the different approaches used to calculate
      safe limits for selenium. As recommended by WHO, the guidelines for drinking
      water form the basis of national legislated standards for drinking water. Before
      setting a maximum acceptable level in drinking water, it is necessary to take
      into account the total intake of selenium in both food and beverage. The limit
      value of 10 microg l(-1) for drinking water laid down in the European regulations
      for all countries should be adapted depending on geographic area, as previously
      recommended by WHO.

PMID- 19590131
TI  - Bacteriological quality and risk assessment of the imported and domestic bottled
      mineral water sold in Fiji.
AB  - Considering the popularity of bottled mineral water among indigenous Fijians and
      tourists alike, a study was carried out to determine the bacteriological quality
      of different bottled waters. A risk assessment was also carried out. Seventy-five
      samples of bottled mineral water belonging to three domestic brands and 25
      samples of one imported brand were analysed for heterotrophic plate count (HPC)
      bacteria and faecal coliforms. HPC counts were determined at 22 degrees C and 37
      degrees C using R2A medium and a membrane filtration technique was used to
      determine the faecal coliform (FC) load in 100 ml of water on mFC agar. Between
      28 and 68% of the samples of the various domestic brands failed to meet the WHO
      standard of 100 colony forming units (cfu) per 100 ml at 22 degrees C and 7% of
      these also tested positive for faecal coliforms. All imported bottled mineral
      water samples were within WHO standards. A risk assessment of the HPC bacteria
      was carried out in terms of beta haemolytic activity and antibiotic resistance.
      More than 50% of the isolates showed beta haemolytic activity and were multi-drug
      resistant. While the overall quality of the product was generally good, there is
      a need to enforce stringent quality standards for the domestic bottlers to ensure
      the safety of consumers.

PMID- 19590132
TI  - Evaluation of four cell lines for assay of infectious adenoviruses in water
      samples.
AB  - Human viral contamination in drinking and recreational waters poses health risks.
      The application of PCR-based molecular technology has advanced our knowledge of
      the occurrence and prevalence of human viruses in water; however, it has provided
      no information on viral viability and infectivity. Four human cell lines were
      compared for their sensitivity to different serotypes of human adenoviruses using
      the TCID50 test. The sensitivity of each cell line varied with different
      serotypes of adenovirus. Human embryonic kidney cell line 293A and human lung
      carcinoma cell line A549 were the most sensitive, especially to enteric
      adenovirus 40 and 41. Plaque assay of primary sewage samples showed 293A can
      detect viral plaques in 7 of 13 primary sewage samples tested. Adenoviruses were
      also isolated using 293A from environmental water concentrates. Cloning and
      sequencing of environmental adenoviral isolates indentified them to be aligned
      with adenoviruses serotype 40 and serotype 5. The result of this study suggests
      that plaque assay with 293A cell line is suitable for detection of adenovirus in
      the aquatic environment. Combining this cell culture with molecular methods for
      viral assay in the aquatic environment will provide critical information for risk
      assessment.

PMID- 19590133
TI  - Bactericidal activity of Ag nanoparticle-impregnated fibreglass for water
      disinfection.
AB  - A new bactericidal system composed of fibreglass impregnated with silver (Ag)
      nanoparticles was developed and tested. Silver content, particle size and
      distribution were characterized by scanning electron microscopy (SEM) and X-ray
      diffraction (XRD). The antibacterial effectiveness was evaluated against
      Escherichia coli (E. coli, ATCC 29055). The minimum inhibitory loading was
      determined to be less than 1.8 wt% of silver nanoparticles per gram of
      fibreglass. In a 1 h immersion test, using a 0.1 mg fibreglass mat ml(-1), with
      2.9 wt% loading of silver nanoparticles completely disinfected 100 ml of 10(6)
      CFU ml(-1) of E. coli, dramatically outperforming activated carbon fibres
      impregnated with silver. Inactivation rate studies of 0.05 mg fibreglass mat ml(
      1) (Ag 1.8 wt%) with 10(12) CFU E. coli displayed a 7 log reduction in 5 minutes.
      The activation and reuse of fibreglass (Ag 4.3 wt%) maintained its full
      effectiveness after two cycles of use and thermal regeneration at 350 degrees C.

PMID- 19590134
TI  - Hepatitis E virus genotype 3 and sporadically also genotype 1 circulate in the
      population of Catalonia, Spain.
AB  - Autochthonous hepatitis E virus (HEV) strains have been described infecting
      populations of industrialized countries, previously considered as non-endemic
      areas. The HEV strains circulating in one of those areas in south-western Europe
      (Barcelona, Spain) have been studied by analysing amplicons obtained from HEV
      genomes identified in wastewater, biosolids and sludge. Six sewage and two
      biosolid HEV positive samples from urban wastewater treatment plants and two
      positive HEV sludge samples with animal contamination were analysed by cloning
      and sequencing of 10-12 clones per sample. The results proved the presence of HEV
      strains belonging to genotype 3 and also sporadically to genotype 1 in urban
      sewage and biosolids, showing the simultaneous circulation of diverse HEV strains
      in the human population of the studied area. Only HEV genotype 3 was identified
      in slaughterhouse sludge samples. The circulation of genotype 1 in industrialized
      areas may have further health implications since this genotype has been
      associated with important epidemics in developing areas. Contamination of food
      and water through their contact with sewage not properly treated and biosolids
      presenting HEV may represent a significant risk for human populations in relation
      to HEV even in industrialized areas.

PMID- 19590135
TI  - Rapid dead-end ultrafiltration concentration and biosensor detection of
      enterococci from beach waters of Southern California.
AB  - Same-day microbial water quality assessments are not possible with standard
      methods, which increases the possibility of public exposure to fecal pathogens.
      This study examined the efficacy of high-volume hollow fibre ultrafiltration
      coupled to biosensor detection for enterococci in marine waters to allow same-day
      public notification of poor water quality. Fifty-six 1001 ultrafiltered samples
      and 100 ml grab samples were collected weekly from May to July 2007. Post
      ultrafiltration processing included sonication and micron sieve passage to remove
      interfering particulates, followed by centrifugation for secondary concentration.
      Levels of enterococci in grab and ultrafiltration samples were determined by a
      standard method (EPA method 1600) for calculation of recovery efficiencies and
      concentration factors. Each final retentate was analysed with the RAPTOR
      evanescent wave biosensor. Enterococci levels increased over 26,000-fold in final
      retentates. Enterococci were detected when ambient concentrations exceeded the
      regulatory standard for a single sample (> or = 105 CFU/100 ml), and detection
      was highly correlated with breaches of the single-sample regulatory limit. The
      combined procedure required 2.5 h for detection compared with 24h for EPA method
      1600. This field study achieved rapid detection of enterococci by
      ultrafiltration, secondary concentration and biosensor analysis, and demonstrates
      its potential usefulness for water quality monitoring.

PMID- 19590137
TI  - Where's the pump? Associating sporadic enteric disease with drinking water using
      a geographic information system, in British Columbia, Canada, 1996-2005.
AB  - We investigated whether risk of sporadic enteric disease differs by drinking
      water source and type using surveillance data and a geographic information
      system. We performed a cross-sectional analysis, at the individual level, that
      compared reported cases of enteric disease with drinking water source (surface or
      ground water) and type (municipal or private). We mapped 814 cases of
      campylobacteriosis, cryptosporidiosis, giardiasis, salmonellosis and
      verotoxigenic Escherichia coli infection, in a region of British Columbia,
      Canada, from 1996 to 2005, and determined the water source and type for each
      case's residence. Over the 10-year period, the risk of disease was 5.2 times
      higher for individuals living on land parcels serviced by private wells and 2.3
      times higher for individuals living on land parcels serviced by the municipal
      surface/ground water mixed system, than the municipal ground water system. Rates
      of sporadic enteric disease potentially differ by drinking water source and type.
      Geographic information system technology and surveillance data are accessible to
      local public health authorities and used together are an efficient and affordable
      way to assess the role of drinking water in sporadic enteric disease.

PMID- 19590136
TI  - Molecular detection of enterotoxins in environmental strains of Aeromonas
      hydrophila and Aeromonas jandaei.
AB  - Aeromonas species are widely distributed in aquatic environments and recent
      studies include the genus in the emergent pathogens group because of its frequent
      association with local and systemic infections in immunocompetent humans. Aiming
      to search for virulence genes in environmental strains of Aeromonas hydrophila
      and Aeromonas jandaei, we designed specific primers to detect act/hlyA/aer
      complex and alt genes. Primers described elsewhere were used to detect ast.
      Eighty-seven strains previously identified using phenotypic and genotypic tests
      as A. hydrophila (41) and A. jandaei (46) were analysed for the presence of the
      virulence genes using PCR. DNA fragments of expected size were purified and
      directly sequenced. Among the 41 strains of A. hydrophila 70.7% (29), 97.6% (40)
      and 26.8% (11) possessed act/hlyA/aer complex, ast and alt genes, respectively.
      Among the 46 strains of A. jandaei, 4.4% (2), 0% (0) and 32.6% (15) were positive
      for act/hly A/aer complex, ast and alt genes, respectively. Sequencing allowed
      for the confirmation of amplified products using BLAST. The present work proposes
      a specific and rapid diagnostic method to detect the main virulence determinants
      of Aeromonas, a genus potentially pathogenic to humans.

PMID- 19590138
TI  - Mathematical models for Enterococcus faecalis recovery after microwave water
      disinfection.
AB  - Microwave water disinfection is a rapid purification technique which can give
      billions of people access to clean drinking water. However, better understanding
      of bacterial recovery after microwave heating over time is necessary to determine
      parameters such as delayed bacterial growth rates and maximum bacterial yields.
      Mathematical models for Enterococcus faecalis recovery after microwave treatment
      in optimum growth conditions were developed for times up to 5 minutes using an
      optical absorbance method. Microwave times below 3 minutes (2,450 MHz, 130W)
      showed that bacterial recovery maintained a time-dependent sigmoidal form which
      included a maximum value. At microwave times greater than three minutes,
      bacterial recovery, with a time-dependent exponential form, significantly
      decreased and did not reach the maximum value within the interval of observance
      (0-8 hours). No bacterial growth was found after 6 minutes of microwave
      treatment. The prepared mathematical models were produced by transforming the
      given variables to the logistic or exponential functions. We found that time
      dependent maximum growth rates and lag times could be approximated with second
      order polynomial functions. The determined models can be used as a template to
      illustrate bacterial survival during water purification using microwave
      irradiation, in both commercial and industrial processes.

PMID- 19590139
TI  - Clinical impact of atrial fibrillation in patients with hypertrophic
      cardiomyopathy. Results from Kochi RYOMA Study.
AB  - BACKGROUND: There have been few studies of the clinical features of hypertrophic
      cardiomyopathy (HCM) in a community-based patient cohort in Japan. METHODS AND
      RESULTS: Cardiomyopathy registration was established in Kochi Prefecture and
      named the Kochi RYOMA (registry of myocardial diseases) study, consisting of 9
      hospitals that registered 261 patients with a diagnosis of HCM. At registration,
      74 patients (28%) had documented paroxysmal or chronic atrial fibrillation (AF).
      Although most patients (93%) were in New York Heart Association (NYHA) class I or
      II, 17 of the 18 patients in NYHA III had AF; 37 of the 74 patients with AF
      suffered from morbid events (embolism and/or heart failure (HF) admission), and
      15 of 19 patients with embolic events had AF prior to or at the time of embolism.
      Of the 29 patients who had a history of HF admission, 8 had left ventricular
      systolic dysfunction, and the other 21 patients were hospitalized because of
      diastolic HF. AF occurred prior to HF in 20 of those 21 patients. Furthermore, 19
      of those 20 patients with AF and diastolic HF were hospitalized within 1 year
      after detection of AF. CONCLUSIONS: In an unselected regional registry, AF was
      the major determinant of clinical deteriorations in patients with HCM.

PMID- 19590140
TI  - Evidence for Rho-kinase activation in patients with pulmonary arterial
      hypertension.
AB  - BACKGROUND: Direct evidence for Rho-kinase activation in patients with pulmonary
      hypertension (PH) is still lacking. METHODS AND RESULTS: Rho-kinase activity in
      circulating neutrophils was examined by determining the ratio of
      phosphorylated/total forms of myosin-binding subunit, a substrate of Rho-kinase,
      in 40 consecutive PH patients and 40 healthy controls. Next, Rho-kinase
      expression and activity was examined in isolated human lung tissues (5 patients
      with idiopathic pulmonary arterial hypertension [IPAH], 5 controls) and vascular
      reactivity of isolated small human pulmonary arteries in vitro (4 IPAH, 4
      controls). Rho-kinase activity in circulating neutrophils was significantly
      increased in the PH patients overall compared with controls (P<0.0001).
      Significant correlations were noted between Rho-kinase activity and the severity
      and duration of PAH (all P<0.05). Rho-kinase expression and activity in isolated
      lung tissues also were significantly increased in the IPAH patients compared with
      the controls (both P<0.0001). Endothelium-dependent relaxation was markedly
      impaired and serotonin-induced contraction (in the absence of the endothelium)
      markedly enhanced in the PAH patients compared with the controls, and the
      hypercontraction to serotonin was abolished by hydroxyfasudil, a specific Rho
      kinase inhibitor. CONCLUSIONS: These results provide the first direct evidence
      for Rho-kinase activation in patients with PAH, suggesting the therapeutic
      importance of Rho-kinase in the disorder.

PMID- 19590141
TI  - Ischemia enhances translocation of connexin43 and gap junction intercellular
      communication, thereby propagating contraction band necrosis after reperfusion.
AB  - BACKGROUND: In ischemia-reperfusion, contraction band necrosis (CBN) is
      distributed mainly to the lateral border of the risk area and does not spread
      into the non-risk area beyond the border. It has been suggested that CBN is
      propagated through gap junctions (GJs), but it is unclear how GJs transmit CBN
      exclusively in the risk area. METHODS AND RESULTS: Coronary occlusion for 30 min
      in rat increased the level of connexin43 (Cx43) protein in the 100,000 x g pellet
      fraction to 1.5-fold and decreased that in the 1,000 x g pellet to half in the
      risk area compared with the non-risk area. Immunohistochemical analysis showed an
      increase of Cx43 at intercalated disks in the risk area. A dye transfer assay
      demonstrated enhancement of GJ intercellular communication (GJIC) in the risk
      area compared with the non-risk area in the same section. Administration of a GJ
      blocker, carbenoxolone, at the onset of reperfusion following 30 min of ischemia
      reduced the CBN area (1/3 vs PBS) in 5 min of reperfusion and limited the infarct
      size (2/3 vs PBS) in 6 h of reperfusion. CONCLUSIONS: These data suggest that
      ischemia enhances translocation of Cx43 to GJs, thereby promoting propagation of
      CBN exclusively in the risk area through enhanced GJIC after reperfusion.

PMID- 19590142
TI  - Associations between metabolic syndrome and mortality from cardiovascular disease
      in Japanese general population, findings on overweight and non-overweight
      individuals. Ibaraki Prefectural Health Study.
AB  - BACKGROUND: The impact of being overweight, as a component of the metabolic
      syndrome (MetS), for cardiovascular disease (CVD) mortality was investigated and
      compared with the predictive value of MetS by 2 different definitions. METHODS
      AND RESULTS: A 12-year prospective study of 30,774 Japanese men and 60,383 women
      aged 40-79 years was conducted. The multivariate hazard ratio (HR; 95% confidence
      interval) of total CVD mortality for overweight subjects with >or=2 additional
      risk factors with reference to subjects with 0 of 4 MetS components was 1.83
      (1.41-2.38) for men and 1.90 (1.45-2.49) for women, and for non-overweight
      subjects with >or=2 additional risk factors 1.75 (1.38-2.24) and 1.97 (1.52
      2.55), respectively. The proportion of excess CVD deaths in the latter group was
      1.5-fold higher than that in the former group. Multivariate HRs of coronary heart
      disease and total CVD mortality for MetS by the modified criteria of the American
      Heart Association/National Heart, Lung, and Blood Institute were 1.62 (1.31-2.00)
      and 1.23 (1.09-1.39), respectively, for men and 1.32 (1.05-1.65) and 1.12 (1.00
      1.25), respectively, for women. The respective HRs for MetS by the International
      Diabetic Federation definition did not reach statistical significance, except for
      coronary heart disease in men. CONCLUSIONS: Non-overweight individuals with
      metabolic risk factors, as well as overweight individuals with such factors,
      should be targeted to reduce the CVD burden in the general population.

PMID- 19590144
TI  - Medium optimization by orthogonal array and response surface methodology for
      cholesterol oxidase production by Streptomyces lavendulae NCIM 2499.
AB  - This paper deals with the optimization of culture conditions for the production
      of cholesterol oxidase (COD) by Streptomyces lavendulae NCIM 2499 using the one
      factor-at-a-time method, orthogonal array method and response surface methodology
      (RSM) approaches. The one-factor-at-a-time method was adopted to investigate the
      effects of medium components (i.e. carbon and nitrogen) and environmental factors
      (i.e. initial pH) on biomass growth and COD production. Subsequently, an L12
      orthogonal matrix was used to evaluate the significance of glycerol, soyabean
      meal, malt extract, K2HPO4, MgSO4 and NaCl. The effects of media components were
      ranked according to their effects on the production of COD as malt extract >
      soyabean meal > K2HPO4 > NaCl > MgSO4 > glycerol. The subsequent optimization of
      the four most significant factors viz. malt extract, soyabean meal, K2HPO4 and
      NaCl, was carried out by employing a central composite rotatable design (CCRD) of
      RSM. There was a 2.48-fold increase in productivity of COD as compared to the
      unoptimized media by using these statistical approaches.

PMID- 19590145
TI  - Rapid identification of lactic acid bacteria isolated from home-made fermented
      milk in Tibet.
AB  - Fermented milk is a very delicious and nutritional food distributed in the
      international markets. Rapid preliminary identification of lactic acid bacteria
      to the species level is an important issue for the fermentation industry. One
      hundred seventy-one strains of lactic acid bacteria (LAB) were isolated from
      twenty-nine kurut samples and fifteen traditional fermented mongolian cattle milk
      (FMCM) samples in Tibet, China. All of the strains were isolated and divided into
      bacilli or cocci by phenotype, and then differentiated by restriction fragment
      length polymorphism (RFLP) analysis using a set of restriction enzymes, AluI,
      HaeIII, BsmaI, TspRI and HinfI. Restriction pattern analyses indicated that the
      lactobacilli could be clearly identified at the species level and the LAB cocci
      at the genera level by the five restriction enzymes. Further studies on 16S rDNA
      sequences of representative and undefined strains showed that the combination of
      RFLP analysis of polymerase chain reaction (PCR) for amplifying 16S rDNA and 16S
      rDNA sequence analysis is rapid, easy to perform, and effective for large-scale
      preliminary identification of LAB.

PMID- 19590147
TI  - Ilumatobacter fluminis gen. nov., sp. nov., a novel actinobacterium isolated from
      the sediment of an estuary.
AB  - Bacterial strain YM22-133T was isolated from the sediment of an estuary and grew
      in media with an artificial seawater base. Strain YM22-133T was Gram-positive,
      aerobic, non-motile and rod shaped. The cell-wall peptidoglycan contained LL-DAP,
      glycine, alanine and hydroxyglutamate. The predominant menaquinone was MK-9 (H8),
      with MK-9 (H0), MK-9 (H2), MK-9 (H4) and MK-9 (H6) present as minor menaquinones.
      The G+C content of the genomic DNA from the strain was 68 mol%. Phylogenetic
      analysis of the 16S rRNA gene sequence showed that the strain is nearest to
      Acidimicrobium ferrooxidans DSM 10331T. However, the similarity is relatively low
      (87.1%) and the physiological characteristics are also different: Acidimicrobium
      ferrooxidans is thermotolerant and acidophilic. Therefore, strain YM22-133T can
      be classified as a novel genus and species, Ilumatobacter fluminis gen. nov., sp.
      nov. (type strain YM22-133T = DSM 18936T = MBIC 08263T).

PMID- 19590146
TI  - Identification and characterization of the AcrR/AcrAB system of a pathogenic
      Edwardsiella tarda strain.
AB  - Edwardsiella tarda is one of the leading marine pathogens that can infect a wide
      range of cultured marine species. In this study, the acrR-acrAB cluster was
      cloned from TX1, a pathogenic E. tarda strain isolated from diseased fish. AcrR
      and AcrAB were found to be involved in resistance against acriflavine and methyl
      viologen, which positively regulate the expression of acrAB. AcrR negatively
      regulates its own expression and the expression of the acrAB operon, most likely
      by interacting with a 24-bp operator site that overlaps the putative promoter of
      acrA (P(acrA)). The repressive effect of AcrR on P(acrA) could be relieved by
      acriflavine, methyl viologen, and ethidium bromide, the presence of each of which
      enhanced transcription from P(acrA). Interruption of the regulated expression of
      acrR by introducing into TX1 a plasmid that overexpresses acrR affected growth
      under stress conditions, AI-2 production, and bacterial virulence. In addition,
      mutational analyses identified a constitutively active AcrR mutant (named N215),
      which exhibits full repressor activity but is impaired in its ability to interact
      with the inducer. Overexpression of N215 produced the same kind of but moderately
      stronger effect on TX1 compared to that produced by overexpression of the wild
      type acrR.

PMID- 19590148
TI  - Phenotypic and molecular characterization of a novel beta-lactamase carried by
      Klebsiella pneumoniae, CTX-M-72, derived from CTX-M-3.
AB  - This study reports phenotypic and molecular characterization of a novel CTX-M
      beta-lactamase carried by two Klebsiella pneumoniae isolates collected from two
      hospitals in China. Conjugation experiment, Southern hybridization,
      susceptibility testing, isoelectric focusing, PCR, and sequencing techniques as
      well as clone, expression, purification and kinetics were carried out to describe
      the characterization of the novel CTX-M-type enzyme. The analyses of plasmid
      profiling and pulsed-field gel electrophoresis of the novel enzyme were performed
      to investigate epidemiology. The PCR products had 967 nucleotides and a novel CTX
      M enzyme with a pI of 8.5 was implicated in this resistance: CTX-M-72. Two
      strains exhibited a clavulanic acid-inhibited substrate profile that included
      extended-spectrum cephalosporins. The amino acid sequence of the CTX-M-72 beta
      lactamase differed from that of the CTX-M-3 beta-lactamase by the Arg-->Gly
      change at position 164. The novel enzyme was susceptible to ceftazidime, the same
      response being observed for other CTX-M enzymes. The substrates of the beta
      lactamase were also characterized. Furthermore, two resistant genes of clinical
      strains were closely related. The emergence of a novel CTX-M-type extended
      spectrum beta-lactamase was rarely described in other areas. This study
      illustrated the importance of molecular surveillance in tracking CTX-M-producing
      strains in large teaching hospitals, suggested the horizontal transfer of plasmid
      borne bla(CTX-M) genes contributed to the dissemination of CTX-M enzymes in
      hospital environments, and emphasized the need for epidemiological monitoring.

PMID- 19590149
TI  - Sporosarcina luteola sp. nov. isolated from soy sauce production equipment in
      Japan.
AB  - A Gram-variable, spore-forming, motile rod, designated strain Y1T, was isolated
      from the hopper surface of equipment used for soy sauce production. Phylogenetic
      analysis based on 16S rRNA gene sequence revealed that Y1T is affiliated
      phylogenetically to the genus Sporosarcina, and the strain showed sequence
      similarities of 95.8-99.2% to those of Sporosarcina species with validly
      published names. The values of DNA-DNA relatedness between strain Y1T and related
      type strains of the genus Sporosarcina were below 27%. The major cellular fatty
      acids were iso-C(15:0) and anteiso-C(15:0). The cell-wall peptidoglycan was of
      the A4alpha type (Lys-Glu) and the major isoprenoid quinone was MK-7. The major
      polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and
      phosphatidylethanolamine. The genomic DNA G+C content of the strain was 43.6
      mol%. On the basis of phylogenetic analysis and physiological and chemotaxonomic
      data, the isolate represents a novel species of the genus Sporosarcina, for which
      the name Sporosarcina luteola sp. nov. is proposed. The type strain is strain Y1T
      (= JCM 15791T = NRRL B-59180T = NBRC 105378T = CIP 109917T = NCIMB 14541T).

PMID- 19590150
TI  - Oceanobacillus soja sp. nov. isolated from soy sauce production equipment in
      Japan.
AB  - A Gram-positive, spore-forming, motile rod-shaped bacterium, designated strain
      Y27T, was isolated from the bottom of a mold fermenter used in the process of soy
      sauce production. Phylogenetic analysis of the 16S rRNA gene sequence from this
      strain placed it within the genus Oceanobacillus, and further sequence analysis
      revealed that this strain has a sequence similarity of 95.0-98.7% to other known
      species of Oceanobacillus. The DNA-DNA relatedness between strain Y27T and
      related type strains of the genus Oceanobacillus is below 43%, indicating that it
      should be considered a separate species. Characterization of strain Y27T revealed
      that the major cellular fatty acid is anteiso-C(15:0), the cell wall contains
      meso-diaminopimelic acid-type peptidoglycans, the major menaquinone is MK-7, and
      the major polar lipids are diphosphatidylglycerol and phosphatidylglycerol. The
      genomic DNA G+C content of the strain is 38.0 mol%. On the basis of these
      phylogenetic, physiological and chemotaxonomic data, we propose that this isolate
      represents a novel species of the genus Oceanobacillus, and propose the name
      Oceanobacillus soja sp. nov. The type strain is strain Y27T (= JCM 15792T = NRRL
      B-59181T = NBRC 105379T = NCIMB 14542T).

PMID- 19590151
TI  - Bacterial diversity associated with empty oil palm fruit bunch compost as
      revealed by cultivation-independent analyses of PCR-amplified 16S rRNA genes.

PMID- 19590152
TI  - Cloning and molecular characterization of chitinase from Bacillus licheniformis
      MS-3.

PMID- 19590153
TI  - Gluconobacter kanchanaburiensis sp. nov., a brown pigment-producing acetic acid
      bacterium for Thai isolates in the Alphaproteobacteria.

PMID- 19590154
TI  - Extracellular tannase production by endophytic Hyalopus sp.

PMID- 19590155
TI  - Outdoor workers' perceptions of the risks of excess sun-exposure.
AB  - OBJECTIVES: To describe the pattern of associations with sunscreen use of sun
      protection attitudes and knowledge in a large sample of New Zealand outdoor
      workers. We also examined the relationship between perceived skin type and
      perceived risk of developing skin cancer. METHODS: Outdoor workers from nine
      occupational groups (n=1,131) completed a questionnaire, which included measures
      of skin cancer related risk perceptions, knowledge and sunscreen use. RESULTS:
      Sunscreen use was associated with perceived prioritization of sun-protection,
      concern about sun-exposure, knowledge about the effects of sun-exposure and
      perceived supportive workplace culture. These variables accounted for 37% of the
      variation in sunscreen use. Maori, younger workers and forestry workers least
      likely to report sunscreen use and sun-exposure risk perception. CONCLUSIONS:
      Interventions that strengthen knowledge about risks and values of sun protection
      are likely to increase sun protection efforts. However, interventions for outdoor
      workers need to take into account potential socio-demographic, personal and
      workplace influences are required to prevent the risk of developing non-melanoma
      skin cancers within this population group.

PMID- 19590156
TI  - Occupational stress and burnout of lawyers.
AB  - OBJECTIVE: The aim of this study was to explore the associations between burnout
      and occupational stress measured by demand-control support (DCS) and effort
      reward imbalance (ERI) models among lawyers. METHODS: This cross-sectional study
      included 180 lawyers from 26 law firms in the Taipei Bar. The Chinese version of
      Karasek's job content questionnaire (C-JCQ) and the Chinese version of Siegrist's
      ERI questionnaire (C-ERI) were used to measure occupational stress, and the
      Chinese version of the Copenhagen Burnout Inventory (C-CBI) questionnaire was
      used to measure personal, work-related and client-related burnout. Logistic
      regression analysis was used to determine the associations between burnout and
      lawyers' occupational stress and job specialty adjusting for age, gender, marital
      status, work experience, working hours per day, firm size and the significant
      occupational stress of each model for the other. RESULTS: Lawyers reported
      relatively higher scores in job control, psychological demands and effort, and
      high prevalence of self-perceived work stress. Litigious lawyers had higher
      decision authority and workplace social support, higher work-related burnout and
      higher client-related burnout than non-litigious lawyers. Personal burnout and
      work-related burnout were associated with high psychological demands, effort, and
      effort-reward ratio. CONCLUSIONS: High occupational stress was associated with
      high levels of personal and work-related burnout among lawyers.

PMID- 19590157
TI  - Effects of nasal continuous positive airway pressure treatment on oxidative
      stress and adiponectin levels in obese patients with obstructive sleep apnea.
AB  - BACKGROUND: Obesity and obstructive sleep apnea (OSA) are both associated with
      the prevalence of major cardiovascular illnesses and certain common factors they
      are considered responsible for, such as stress oxidative increase, sympathetic
      tonus and resistance to insulin. OBJECTIVE: The aim of the present study was to
      compare the effect of continuous positive airway pressure (CPAP) on oxidative
      stress and adiponectin levels in obese patients with and without OSA. METHODS:
      Twenty-nine obese patients were categorized into 3 groups: group 1: 10
      individuals without OSA (apnea-hypopnea index, AHI <or=5) who did not have OSA
      diagnosed at polysomnography; group 2: 10 patients with moderate to severe OSA
      (AHI >or=20) who did not use CPAP; group 3: 9 patients with moderate to severe
      OSA (AHI >or=20) who used CPAP. RESULTS: Group 3 showed significant differences
      before and after the use of CPAP, in the variables of diminished production of
      superoxide, and increased nitrite and nitrate synthesis and adiponectin levels.
      Positive correlations were seen between the AHI and the superoxide production,
      between the nitrite and nitrate levels and the adiponectin levels, between
      superoxide production and the HOMA-IR, and between AHI and the HOMA-IR. Negative
      correlations were found between AHI and the nitrite and nitrate levels, between
      the superoxide production and that of nitric oxide, between the superoxide
      production and the adiponectin levels, between AHI and the adiponectin levels,
      and between the nitrite and nitrate levels and the HOMA-IR. CONCLUSIONS: This
      study demonstrates that the use of CPAP can reverse the increased superoxide
      production, the diminished serum nitrite, nitrate and plasma adiponectin levels,
      and the metabolic changes existing in obese patients with OSA.

PMID- 19590158
TI  - Effects of inhalation of thermal water on exhaled breath condensate in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Inhalation of thermal water (TW) is traditionally used as part of the
      treatment of chronic obstructive pulmonary disease (COPD), but its benefit and
      mechanisms are controversial. We previously observed a reduced proportion of
      neutrophils in induced sputum after treatment with TW. OBJECTIVES: The aim of
      this study was to determine whether inhalation of TW in COPD patients is
      associated with biochemical changes of airway lining fluid, including a reduction
      in the neutrophil chemoattractant leukotriene B(4) (LTB(4)). METHODS: Thirteen
      COPD patients were randomly assigned to receive a 2-week course of TW and normal
      saline inhalation in a cross-over, single-blind study design. Exhaled breath
      condensate (EBC) was collected before and after treatments. LTB(4) concentrations
      in EBC were determined by ELISA, and EBC pH was measured before and after argon
      deaeration. RESULTS: No significant differences in LTB(4) concentrations in EBC
      were detected with either treatment. A significant decrease in pH of non
      deaerated EBC was observed after a standard course of TW (median 7.45,
      interquartile range 6.93-7.66, vs. median 6.99, interquartile range 6.57-7.19; p
      = 0.05), which disappeared after argon deaeration. CONCLUSIONS: There is no
      evidence that TW treatment affects LTB(4) concentration in EBC. The results of
      EBC pH measurements suggest that TW inhalation induces an imbalance of volatile
      components of the buffer system in airway lining fluid.

PMID- 19590159
TI  - Impact of training modality on strength and physical function in older adults.
AB  - BACKGROUND: The importance of maintaining strength in older adults is well
      documented and various training modalities have been recommended; however, the
      effectiveness of various interventions with high translation to public health
      practice has not been completely characterized. Additionally, the interrelations
      among mode, strength, and lower extremity physical function (LEPF) changes in
      older adults warrant further investigation. PURPOSE: The primary aims were to
      examine the effectiveness of cardiovascular endurance training (CVE) compared
      with balance and flexibility training (FLEX) and to explore the relationship of
      muscle strength to LEPF. METHODS: Fifty-five adults (69.1 +/- 5.6 years, 35
      female) were randomly assigned to 10 months of CVE or FLEX. Knee extension and
      flexion at 60 and 120 degrees s(-1) were measured using an isokinetic
      dynamometer. LEPF was measured using a battery of tasks. The CVE group exercised
      using treadmills, cycles, and elliptical trainers. The FLEX group participated in
      a group exercise class that incorporated flexibility and balance activities.
      RESULTS: The CVE training group significantly improved peak oxygen consumption by
      6% (p = 0.03), while the FLEX training group showed no change (p = 0.47).
      Participants significantly improved peak torque at both speeds and muscle actions
      by 21-65% (p <or= 0.05), with no group effect (p > 0.05). Both groups also
      significantly improved performance on all LEPF tasks included in this study (4
      7%, p <or= 0.05). Significant correlations (all p = 0.00) were found between
      improvements in strength and improvements in LEPF including timed walk and peak
      torque extension and flexion at 60 degrees s(-1) (r = 0.40 and 0.27,
      respectively), obstacle walk and peak torque extension and flexion at 60 and 120
      degrees s(-1) (r range 0.27-0.40), and stair ascent and peak torque extension at
      120 degrees s(-1) (r = 0.37). CONCLUSIONS: Sedentary older adults achieve similar
      improvements in strength and LEPF with either CVE or FLEX training with the
      latter being related to improvements in leg strength.

PMID- 19590160
TI  - Seasonal and cyclical change in the luteinizing hormone response to kisspeptin in
      the ewe.
AB  - BACKGROUND: Kisspeptins are recognized as important stimulators of gonadotropin
      releasing hormone (GnRH) and gonadotropin secretion. In sheep, the nonbreeding
      (anestrous) period is characterized by reduced Kiss1 mRNA expression in the
      hypothalamus. The aim of the present study was to determine whether the response
      to kisspeptin treatment varies between the breeding and nonbreeding seasons.
      METHODS: Corriedale ewes were treated intravenously with murine kisspeptin-10
      (submaximal dose: 20 microg or maximal dose: 250 microg) or GnRH (250 ng) during
      either the anestrous period or during the breeding season at the luteal, mid
      follicular, or late-follicular phase of the estrous cycle. RESULTS: Kisspeptin
      treatment increased the concentration of luteinizing hormone (LH) in all animals.
      We found the LH response to kisspeptin (20 microg) was greater in ewes during the
      anestrous period, being 4-fold that seen during the luteal phase of the estrous
      cycle. Within the breeding season, kisspeptin (20 microg) was most effective
      during the late-follicular phase of the estrous cycle. Kisspeptin treatment (both
      20 and 250 microg) had no effect on plasma levels of growth hormone, prolactin or
      cortisol. The variable effect of kisspeptin (20 microg) on LH secretion appeared
      to mirror that of GnRH treatment indicating that the effect may be mediated by a
      change in the pituitary response to GnRH. CONCLUSION: We conclude that the
      gonadotropic response to kisspeptin depends upon the reproductive status of the
      female.

PMID- 19590162
TI  - Targeted radionuclide therapy for neuroendocrine tumours: principles and
      application.
AB  - Neuroendocrine tumours comprise a group of neoplasms with variable clinical
      behaviour. Their growth and spread is often very slow and initially asymptomatic,
      and thus they are often metastatic at the time of diagnosis and incurable by
      surgery. An exciting therapeutic strategy for cytoreduction, both for
      stabilisation of tumour growth and inhibition of hormone production, is the use
      of targeted radionuclide therapy. Evidence from large-scale, randomised, placebo
      controlled trials is very difficult to obtain in these rare diseases, but current
      data appear promising. It is timely to review the principles underlying the use
      of these therapies, together with the clinical outcomes to date and potential
      directions for future research.

PMID- 19590164
TI  - Ex vivo model of cranial suture morphogenesis and fate.
AB  - BACKGROUND/AIMS: Craniosynostosis, the premature fusion of cranial sutures, is a
      common congenital defect. In vivo models for studying cranial suture biology
      impose inherent restrictions on tissue accessibility and manipulation. The
      present study was performed to investigate the utility of the renal capsule assay
      in overcoming these limitations and providing a reproducible model system for
      studying cranial suture morphogenesis and fate. MATERIALS AND METHODS: The
      posterior frontal suture, which fuses physiologically, and the coronal and
      sagittal sutures, which remain patent, were dissected from postnatal and
      embryonic mouse calvaria and placed under the renal capsule of syngeneic
      recipient mice (n = 72 in total). Sutures were harvested from 1-14 days after
      transplantation for histological and morphometric analysis. Suture transplants
      were compared with nonmanipulated sutures at equivalent developmental stages. The
      derivation of cells associated with the growing transplants was analyzed using
      beta-actin-GFP (green fluorescent protein) transgenic mice. RESULTS: Sutures
      transplanted under the renal capsule maintained normal suture morphology and fate
      with the posterior frontal suture fusing and the coronal and sagittal sutures
      remaining patent. In posterior frontal suture transplants, the fusion process
      mimicked in vivo suture fusion with a delay of 1-2 days. In comparison to in vivo
      suture complexes, transplant thickness and trabeculation were significantly
      increased. In addition, we found that osteoblasts within the growing transplant
      were derived from the transplant itself rather than the host. CONCLUSION: The
      renal capsule supports the growth of cranial sutures. In this system transplanted
      sutures recapitulate the anatomical development and fate (fusion or patency) of
      cranial sutures in vivo. This model system will facilitate controlled ex vivo
      manipulations of both embryonic and postnatal sutures.

PMID- 19590165
TI  - Blaschkolinear congenital melanocytic nevus.

PMID- 19590161
TI  - Central mineralocorticoid receptors and cardiovascular disease.
AB  - The mineralocorticoid receptor (MR) is expressed in many cell types throughout
      the body, including specific neurons, and mediates diverse functions, many of
      which are just now being appreciated. MR that pertain to the central modulation
      of cardiovascular function and health are addressed herein.

PMID- 19590166
TI  - Methylaminolaevulinate photodynamic therapy in patients with multiple basal cell
      carcinomas in the setting of Gorlin-Goltz syndrome or after radiotherapy.
AB  - BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is a therapeutic
      challenge due to the multiplicity of cutaneous tumours. Photodynamic therapy
      (PDT) is increasingly used as an alternative treatment for superficial and in
      some countries nodular basal cell carcinomas (BCC). OBJECTIVE: To study the
      safety and efficiency of PDT in NBCCS. METHODS: We reviewed retrospectively the
      evolution of 62 lesions from patients with multiple BCC treated with PDT.
      RESULTS: The initial response rate (85.4%, 53/62) and recurrence rate (7.5%)
      appeared comparable to literature values in NBCCS and to those reported in the
      treatment of sporadic BCC. The clearance rate without recurrence was 79% (49/62),
      during a mean follow-up period of 13 months. The cosmetic outcome was excellent.
      Recurrences were found almost 2 years after treatment. CONCLUSION: PDT is a
      suitable therapeutic option in the management of NBCCS patients but requires a
      strict and long follow-up.

PMID- 19590168
TI  - Successful treatment of systemic-sclerosis-related digital ulcers with a
      selective endothelin type A receptor antagonist (sitaxentan).
AB  - Digital ulcers represent a major vascular complication of systemic sclerosis
      (SSc) and can be difficult to treat with the common vasodilators. Herein, we
      report on a 39-year-old patient with recalcitrant SSc-related digital ulcers
      treated successfully with sitaxentan (100 mg q.d.), a selective endothelin type A
      receptor antagonist. During the 6 months of treatment, we noticed a remarkable
      decrease in pain, a nearly complete healing of the preexistent ulcers and no
      development of new ulcers. No side effects were noted.

PMID- 19590167
TI  - Sclerosing nevus with pseudomelanomatous features (nevus with regression-like
      fibrosis): clinical and dermoscopic features of a recently characterized
      histopathologic entity.
AB  - BACKGROUND: Sclerosing nevi with pseudomelanomatous features or, else, nevi with
      regression-like fibrosis (NRLF) are histopathologic simulators of regressing
      melanoma. OBJECTIVE: We aimed at evaluating the clinical features in a series of
      NRLF. METHODS: Dermoscopic images of NRLF were re-evaluated according to the
      amount of regression, the presence of white/blue areas and the 7-point checklist.
      RESULTS: Forty-six lesions from 44 patients (M:F = 3.4:1; mean age: 42 years)
      were evaluated. Thirty-seven lesions were excised from the back, mostly from the
      scapular area. All the lesions were dermoscopically atypical, with large amounts
      of regression (>10% in 43 cases) and with coexistence of white and blue areas (41
      cases). According to the 7-point checklist, 25 lesions were labeled as benign,
      probably because regression obscured other dermoscopic features of atypia.
      CONCLUSION: NRLF are mostly found in the convex area of the back. A better
      recognition of their clinicopathologic features can allow a more conservative
      management.

PMID- 19590169
TI  - Red scalp disease--a rosacea-like dermatosis of the scalp? Successful therapy
      with oral tetracycline.

PMID- 19590170
TI  - Treatment of pigmented purpuric dermatosis with topical photodynamic therapy.

PMID- 19590171
TI  - Intravascular large B-cell lymphoma of the skin: typical clinical manifestations
      and a favourable response to rituximab-containing therapy.
AB  - Intravascular large B-cell lymphoma (IVBCL) is a rare malignant neoplasm
      characterized by the proliferation of large B cells within the blood vessels. The
      disease can be limited to the skin, but involvement of other organs is common. We
      report a case of cutaneous IVBCL in a 62-year-old man with minimal histological
      changes in contrast to prominent skin lesions. The patient was successfully
      treated with rituximab in combination with CHOP chemotherapy.

PMID- 19590172
TI  - Prevalence of body dysmorphic features in patients undergoing cosmetic procedures
      at the National Skin Centre, Singapore.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is characterised by an obsessive
      preoccupation with a slight defect in appearance, and recognition is essential.
      OBJECTIVE: To screen by a previously developed questionnaire the prevalence of
      BDD in an aesthetics clinic in Singapore. This questionnaire has a positive
      predictive value of 70% and a negative predictive value of 100%; patients
      answering that they were preoccupied with their appearance and having answered
      'yes' in part A, answered 8 further questions (part B) grading the degree of
      distress (B4) and impairment (B5) of social functioning. METHODS: The
      questionnaire was given to 396 patients: 198 attending Mandalay Aesthetics Clinic
      and 198 controls at a general outpatient clinic. The screen was considered
      suggestive of BDD if the patients: were preoccupied by their defect (question A)
      and qualified the degree of stress (question B4) or impairment of functioning
      (question B5) as moderate to severe. RESULTS: 58.1% of patients undergoing
      cosmetic procedures answered 'yes' to question A (odds ratio = 18.21, 95%
      confidence interval = 9.87-33.59). 41.74 and 26.96% of those qualified the
      distress (question B4) and impairment (question B5) as moderate to severe.
      CONCLUSION: A calculated prevalence of 29.4% in an aesthetics centre warrants
      systematic screening for BDD.

PMID- 19590174
TI  - The effect of combined treatment with oral clindamycin and oral rifampicin in
      patients with hidradenitis suppurativa.
AB  - BACKGROUND: A previous limited study showed promising results of combined oral
      treatment with rifampicin 600 mg and clindamycin 600 mg for 10 weeks. OBJECTIVE:
      To expand and to validate the basis for this therapy, we reviewed the response to
      different treatment durations. METHOD: A retrospective study in 34 patients.
      RESULTS: Twenty-eight of 34 patients (82%) experienced at least partial
      improvement, and 16 (47%) showed a total remission. The maximum effect of
      treatment appeared within 10 weeks. Following total remission, 8 of 13 (61.5%)
      patients treated as mentioned above experienced a relapse after a mean period of
      5.0 months. Nonresponders were predominantly patients with severe disease.
      CONCLUSION: Combination treatment with oral rifampicin and clindamycin is a
      promising treatment option for hidradenitis suppurativa, despite the frequent
      occurrence of diarrhea as a side effect. The length and the dosage of treatment
      are not yet firmly established.

PMID- 19590173
TI  - Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa:
      a series of 116 consecutive patients.
AB  - BACKGROUND: Antibiotics are frequently used to treat hidradenitis suppurativa
      (HS); however, few data on their efficacy are available. OBJECTIVE: To evaluate
      the efficacy of a combination of systemic clindamycin (300 mg twice daily) and
      rifampicin (600 mg daily) in the treatment of patients with severe HS. METHODS:
      Patients (n = 116) who received this combination were studied retrospectively.
      The main outcome measure was the severity of the disease, assessed by the
      Sartorius score, before and after 10 weeks of treatment. RESULTS: The Sartorius
      score dramatically improved at the end of treatment (median = 29, interquartile
      range = 14.5, vs. median = 14.5, interquartile range = 11; p < 0.001), as did
      other parameters of severity as well as the quality of life score. Eight patients
      (6.9%) stopped the treatment because of side effects. CONCLUSION: The combination
      of clindamycin and rifampicin is effective in the treatment of severe HS.

PMID- 19590175
TI  - Prolactin released in vitro from the pituitary of lactating, pregnant, and
      steroid-treated female or male rats stimulates prolactin secretion from pituitary
      lactotropes of male rats.
AB  - We have previously shown that soluble factor(s) in conditioned media (CM) from
      the central and peripheral regions of the anterior pituitary (AP) gland of
      lactating rats promoted the in vitro dose-related release of prolactin (PRL) from
      pituitary glands of male rats. In the present experiments we sought to determine
      whether CM from rats in different physiological states provoked similar effects
      (like those of lactating rats), and the nature of the factors, whether 23K PRL or
      other variants of the hormone, were responsible for these effects. Stimulatory
      effects were induced by CM from pregnant females and steroid-treated castrated
      males or females, but not from untreated castrated rats, intact males, or by a
      PRL standard. More potent effects occurred with CM from APs of early- than from
      mid- or late-lactating rats, and from rats unsuckled for 8 or 16 h than from
      those unsuckled for 32 h. With respect to the nature of factor(s) responsible for
      these effects, immunoprecipitation of PRL from the CM of lactating females and of
      steroid-treated, castrated males eliminated, whereas dephosphorylation or
      deglycosylation of CM of lactating rats greatly increased its effects upon PRL
      release. Also, electrophoretic analysis and Western blotting of the CM proteins
      under native and denaturing conditions revealed a variety of PRL variants,
      ranging from 14 to <90 kDa, in CM from lactating rats, and the main effects on
      PRL release were provoked by the 23- to 46-kDa PRL variants. These results
      indicate that specific effects upon male rat lactotropes may be exerted by PRL
      variants released from APs of lactating and non-lactating rats.

PMID- 19590176
TI  - Dimethyl sulfoxide-induced toxicity in cord blood stem cell transplantation:
      report of three cases and review of the literature.
AB  - Umbilical cord blood transplantation using nonmyeloablative conditioning is
      currently considered by many as a valid potential alternative for any patient who
      requires an unrelated donor allograft and who is without a suitably matched and
      readily available volunteer. Dimethyl sulfoxide (DMSO) has been used for years as
      a cryoprotectant agent; it acts by penetrating the cell and binding water
      molecules and it has been described as harmless for the individual who receives
      it in limited amounts. In this paper, we describe 3 cases of DMSO-induced
      toxicities and briefly review the most common adverse reactions of the DMSO when
      used as a cryopreservation agent for the long-term storage of cord blood cells.
      Two of the 3 cases had a dismal prognosis. A brief review of the literature is
      presented.

PMID- 19590177
TI  - Advanced glycation end products suppress neuropilin-1 expression in podocytes by
      a reduction in Sp1-dependent transcriptional activity.
AB  - BACKGROUND: Neuropilin-1 (NRP1) is a transmembrane glycoprotein, initially
      defined as a receptor for members of the semaphorin family. We observed that NRP1
      expression was downregulated by the addition of advanced glycation end products
      modified bovine serum albumin (AGE-BSA). The present study was undertaken to
      unravel the molecular mechanisms underlying AGE-BSA-mediated NRP1 suppression.
      METHODS: Expression of NRP1 was analyzed in podocytes. The transcriptional
      activity of the NRP1 promoter was investigated using wild-type and mutant NRP1
      promoter reporter constructs. Electrophoretic mobility assays were performed.
      RESULTS: NRP1 expression was downregulated in podocytes by the addition of AGE
      BSA. In contrast, phorbolester induced NRP1 mRNA and protein expression. The wild
      type promoter transcriptional activity was significantly reduced when podocytes
      were treated with AGE-BSA compared with control, unmodified BSA. Point mutations
      of proximal and distal Sp1-like sites inhibited basal NRP1 promoter activity. AGE
      BSA failed to further suppress transcriptional activity of these constructs.
      Double mutation of the Sp1A and Sp1B binding sites completely abolished NRP1
      transcriptional activity. Gel shift analysis showed a specific binding of the Sp1
      transcription factor. Treatment of podocytes with AGE-BSA revealed a decrease in
      Sp1 binding to consensus sequences, but no effect on AP1 binding. CONCLUSIONS:
      AGE-BSA inhibits NRP1 promoter transcriptional activity in podocytes by reducing
      the binding ability of the Sp1 transcription factor to attach to the NRP1
      promoter.

PMID- 19590178
TI  - Early ontogeny of the olfactory organ in a basal actinopterygian fish:
      polypterus.
AB  - The present study employed light and electron microscopic methods to investigate
      the ontogenetic origin of the olfactory organ in bichirs (Cladistia:
      Polypteridae) and explore its evolution among osteichthyans. In former studies we
      demonstrated that in teleosts a subepidermal layer gives rise to the olfactory
      placode which in turn builds all types of olfactory cells (basal, receptor,
      supporting, ciliated non-sensory cells). In contrast, the olfactory placodes in
      sturgeons (Chondrostei: Acipenseridae) as well as in the clawed frog Xenopus
      laevis (Anura: Pipidae) originate from two different layers. Receptor neurons
      derive from cells of the subepidermal (sensory) layer and supporting cells from
      epidermal cells. As sturgeons and amphibians in some characters show a more
      primitive condition than teleosts, we extended our study to Polypterus to allow
      for an approach at the basic osteichthyan pattern. In Polypterus, an internal
      lumen occurs in early ontogenetic stages surrounded by the epithelium of the
      olfactory placode. Two different populations of supporting cells follow one
      another: a primary population derives from the subepidermal layer. Later
      supporting cells develop from epidermal cells by transdifferentiation. The
      primary opening of the internal lumen to the exterior develops by invagination
      from the epidermal surface and simultaneously by a counter-directed process of
      cell dissociation and fragmentation inside the olfactory placode. Our results
      indicate the following features to be plesiomorphic actinopterygian character
      states: The primary olfactory pit (prospective olfactory cavity) is formed by
      invagination of the epidermal and the subepidermal layer (as in Acipenser and
      Xenopus). The incurrent and excurrent nostrils derive from a single primary
      opening which elongates and is then separated by an epidermal bridge into the two
      external openings (as in Acipenser and many teleosts). The olfactory epithelium
      derives from an epidermal and a subepidermal layer (as in Acipenser and Xenopus).
      Apomorphic (derived actinopterygian) features are: (1) an internal lumen as
      primordium of the future olfactory chamber; (2) a subepidermal layer gives rise
      to the olfactory epithelium and its constituents (Polypterus and teleosts). As to
      the origin of the olfactory supporting cells in Polypterus we assume a
      combination of plesiomorphic and apomorphic characters. We conclude that
      Acipenser and Xenopus exhibit the most widely distributed features among basal
      osteognathostomes and thus ancestral character states in the development of the
      olfactory organs.

PMID- 19590179
TI  - The liver and kidney in critically ill patients.
AB  - Both liver and kidney dysfunction are associated with adverse outcomes in
      critical illness. Advanced liver disease can be complicated by the hepatorenal
      syndrome (HRS) with liver transplantation offering the best long-term outcome.
      However, until recently, HRS was associated with such a poor prognosis that this
      group of patients rarely survived long enough for transplantation to be
      considered. The use of vasopressin analogues and albumin infusions has improved
      the management of HRS and outcomes in terms of renal recovery and survival.

PMID- 19590180
TI  - Continuous hemofiltration in 2009: what is new for clinicians regarding
      pathophysiology, preferred technique and recommended dose?
AB  - In the last years, publications have questioned the classical dose of 35 ml/kg,
      but are those studies strong enough in terms of scientific power in order to
      change our practice? We will try to settle some recommendations for clinicians.
      Manipulation of dose, porosity, and combinations have yielded promising findings.
      However, conclusive evidence based on randomized trials remains scarce, limiting
      the practical implementation in daily practice. From the few designed studies, it
      is safe to say that optimization of delivered dose has a proven positive effect.
      An ultrafiltration rate of around 35 ml/kg/h, with adjustment for predilution,
      can be recommended for the septic patient. Recent studies do not have enough
      power to change this recommendation in view of its shortcomings. Finally the
      recommendation is to keep going with a continuous technique, a pure continuous
      veno-venous hemofiltration mode, and at a dose of 35 ml/kg/h while waiting for
      other studies to be published.

PMID- 19590181
TI  - Increased oxidative stress in hemodialysis patients with high risk for sleep
      apnea syndrome.
AB  - BACKGROUND: In recent years, sleep apnea syndrome (SAS) has been widely
      considered to be a cardiovascular disease (CVD) risk factor. Although several
      plausible mechanisms have been put forth to explain such association in patients
      with SAS, oxidative stress has been suggested to play a major role. In patients
      with SAS, the repetitive ischemia-reperfusion state causes excessive production
      of oxygen free radicals and may subsequently lead to oxidative injury of various
      biomolecules. Due to the high prevalence of SAS in dialysis patients, this
      possible uremia-specific CVD risk factor may definitely need more medical
      attention. METHODS: We, therefore, performed a case control study to investigate
      the relationship between oxidative stress and SAS in a group of dialysis
      patients, using some well-established oxidative biomarkers. RESULTS: Our results
      showed that plasma nitrotyrosine, protein carbonyl and malonaldehyde levels were
      significantly elevated in patients with SAS. Markers of endothelial activation
      such as soluble CD40 ligand were also increased in this subgroup of patients.
      However, there was no significant difference in serum C-reactive protein levels
      between these groups. CONCLUSIONS: Our results indicate that patients with SAS
      manifest evidence for higher oxidative stress and endothelial activation. Thus,
      intermittent hypoxia represents a form of oxidative stress and low-grade chronic
      inflammatory state that may be associated with increased cardiovascular disease
      in these patients.

PMID- 19590182
TI  - A case-control study of single-pass albumin dialysis for acetaminophen-induced
      acute liver failure.
AB  - BACKGROUND: Extracorporeal support with single-pass albumin dialysis (SPAD) may
      remove protein-bound toxins in acute liver failure. We evaluated the clinical,
      physiological and laboratory parameters of SPAD in acetaminophen-induced acute
      liver failure (AALF). METHODS: Retrospective case-control studies of AALF
      patients were used. RESULTS: We identified 13 AALF patients (6 SPAD-treated, 7
      controls). The average age was 38 years, 92% were female, none had cirrhosis and
      the Model for End-Stage Liver Disease (MELD) scores were 43. Eleven patients
      (85%) fulfilled the King's College criteria for a liver transplant. SPAD-treated
      patients received 21 sessions (total: 147 h, mean 3.5 runs or 24.5 h/patient).
      There were no complications. No significant changes in clinical, physiological or
      biochemical parameters occurred during SPAD. Compared with the controls, there
      were no significant differences in ICU or 1-year survival, liver recovery or
      referral for a liver transplant. CONCLUSION: SPAD was well-tolerated in AALF;
      however, it was not associated with differences in clinical outcomes. While SPAD
      may be an adjuvant supportive therapy in AALF, prospective trials are needed.

PMID- 19590183
TI  - Short daily versus conventional hemodialysis quality of life: a cross-sectional
      multicentric study in Spain.
AB  - BACKGROUND: End-stage renal disease is a major health problem worldwide nowadays.
      Although conventional hemodialysis is the most widely used modality, short daily
      hemodialysis has been proposed as a more physiologic treatment. The objective of
      this article is to compare the quality of life of patients on each hemodialysis
      modality. METHODS: A multicentric cross-sectional study was performed in 9
      Spanish hospitals. Patients treated for at least 3 months with conventional or
      short daily hemodialysis were included and quality of life measured using the
      Euroqol-5D quality of life questionnaire. Bayesian models were used for analyzing
      quality of life results. RESULTS: Ninety-three patients were included, 27 were on
      daily hemodialysis and 66 on conventional hemodialysis. All models demonstrated a
      better quality of life for daily hemodialysis versus conventional hemodialysis.
      Only 14% of the patients on conventional hemodialysis were willing to change to a
      daily schedule. CONCLUSIONS: Short daily hemodialysis shows a better quality of
      life than conventional hemodialysis with all Bayesian approaches considered.

PMID- 19590184
TI  - Early diagnosis of acute kidney injury: the promise of novel biomarkers.
AB  - The incidence of acute kidney injury (AKI) formerly referred to as acute renal
      failure (ARF) is increasing to epidemic proportions. Development of AKI portends
      excessive morbidity and mortality. AKI is associated with prolonged hospital
      stay, increased healthcare costs and high mortality especially in critically ill
      patients. The mortality rate has remained largely unchanged for many decades.
      Delay in the diagnosis of AKI using conventional biomarkers like urine output and
      serum creatinine has been one of the important obstacles in applying effective
      early interventions. Several new biomarkers are being evaluated in a quest for
      early diagnosis of AKI, among which neutrophil gelatinase-associated lipocalin
      (NGAL) appears to be one of the most promising. This review summarizes the recent
      literature on these biomarkers.

PMID- 19590185
TI  - Intima-media thickness of the carotid artery and its correlation factors in
      maintenance hemodialysis patients: a cross-sectional study.
AB  - BACKGROUND: To investigate the relationship between the intima-media thickness of
      the carotid artery (CA-IMT) and its major risk factors in maintenance
      hemodialysis (MHD) patients. METHODS: Seventy-five MHD patients and 30 healthy
      volunteers were enrolled. The MHD patients were divided into 3 subgroups
      according to their CA-IMT value. RESULTS: CA-IMT values in the MHD group were
      significantly higher than those in the control group. The differences in age,
      systolic blood pressure (SBP), and levels of serum albumin, prealbumin,
      cholesterol and serum phosphate between the increased IMT group and the normal
      IMT group were significant. SBP and serum phosphate levels were also greater in
      the abnormal IMT group than those in the normal IMT group. Significant
      relationships were found between CA-IMT and age, SBP, and serum levels of
      phosphate, albumin and prealbumin. In multiple regression analysis, a high serum
      phosphate level, low serum prealbumin level and high SBP were significant
      independent risk factors of increased CA-IMT. CONCLUSIONS: CA-IMT was increased
      dramatically in MHD patients. A high serum phosphate level, low serum prealbumin
      level and high SBP may be associated with advanced arteriosclerosis.

PMID- 19590186
TI  - Mechanisms and influence of octreotide-induced regulation of somatostatin
      receptor 2 on hepatocellular carcinoma.
AB  - BACKGROUND: Somatostatin receptors (SSTRs) belong to the family of G protein
      coupled receptors. Exposure of G protein-coupled receptors to their agonists
      induces a rapid decrease in their initial response. The goal of this study is to
      investigate alteration in SSTR2 by the treatment of SSTR agonist octreotide (OCT)
      in hepatocellular carcinoma (HCC) and the resulting consequence. METHODS:
      Morphology, proliferation and cell cycle of the human HCC cell line (Bel7402)
      were evaluated. Effect of OCT on HCC growth and development was assessed in vivo.
      SSTR2 expression was measured by RT-PCR and detected by immunohistochemistry.
      RESULTS: Short-term OCT treatment on Bel7402 cells barely changed cell
      proliferation and morphology, and no apoptosis was induced. The SSTR2 protein
      level was markedly decreased on Bel7402 cells after exposure to OCT. However, the
      weight of the HCC xenograft was significantly lower in the OCT treatment group as
      compared with the control group. In the rat hepatocarcinogenesis model, the
      mortality and incidence of HCC in the OCT treatment group were remarkably less
      than those in the control group. Long-term OCT treatment led to increased levels
      of both SSTR2 mRNA and protein in hepatocytes and HCC cells. CONCLUSION: Short
      term OCT treatment could lead to SSTR2 desensitization, resulting in a reduced
      inhibitory effect on HCC by OCT. However, long-term OCT treatment effectively
      inhibited the development and growth of HCC probably via resensitization and
      upregulation of SSTR2.

PMID- 19590188
TI  - Long QT syndrome-associated mutations in the voltage sensor of I(Ks) channels.
AB  - The plateau phase of the ventricular action potential is the result of balanced
      Ca2+ influx and K+ efflux. The action potential is finally terminated by
      repolarising K+ currents. Under beta-adrenergic stimulation the slowly activating
      component of the human cardiac delayed rectifier K+ current I(Ks) provides the
      major repolarising component. I(Ks) channels are heteromeric channels composed of
      KCNQ1 and KCNE1. Mutations in the voltage sensor S4 of KCNQ1 are associated with
      long-QT syndrome 1 (LQTS1). Here, we study the effects of the mutations S225L,
      I235N and L239P located in S4. The respective channels were expressed in Xenopus
      oocytes and analyzed by dual electrode voltage clamp. As a result all mutants
      shifted the voltage dependence of activation to the right and reduced the voltage
      dependence of deactivation kinetics. The activation kinetics were differently
      affected in homomeric mutant channels compared to wild type KCNQ1. All three
      mutations reduced KCNQ1/KCNE1 channel currents in a dominant-negative manner when
      the mutants were coexpressed with wt subunits suggesting reduced I(Ks) as the
      molecular basis of LQT1.

PMID- 19590189
TI  - Egr-1, the potential target of calcium channel blockers in cardioprotection with
      ischemia/reperfusion injury in rats.
AB  - AIMS: In this study, we tested whether Egr-1 is a potential target of calcium
      channel blockers in cardioprotection with I/R injury. METHODS: We treated rats in
      vivo I/R and rat cultured cardiomyocytes in vitro hypoxia/reoxygenation (H/R)
      models with three types of classical calcium channel blockers (verapamil,
      diltiazem and nifedipine). Activity of creatine kinase (CK), lactate
      dehydrogenase (LDH), myeloperoxidase (MPO) superoxide dismutase (SOD) and level
      of malondialdehyde (MDA) in plasma and culture medium were measured to assess the
      degree of injury and inflammation of myocardial tissues and cells. Egr-1 mRNA and
      protein expressions were examined by RT-PCR and Western-blot analyses. RESULTS:
      Calcium channel blockers (verapamil, diltiazem and nifedipine) significantly
      attenuated myocardial injury, as shown by reduced release of CK and LDH,
      preserved SOD activity and decreased MDA production and MPO activity. Concomitant
      with cardioprotection by calcium channel blockers, the mRNA and protein
      expression of Egr-1 increased with I/R and H/R injury was significantly reduced
      in myocardial tissue and cultured cardiomyocytes. CONCLUSIONS: These results
      suggested that the cardioprotective effects of calcium channel blockers with I/R
      or H/R injury might be mediated by downregulating Egr-1 expression. Egr-1 might
      be the potential target of calcium channel blockers in cardioprotection with
      ischemia/reperfusion injury.

PMID- 19590187
TI  - Excess of glucocorticoid induces cardiac dysfunction via activating angiotensin
      II pathway.
AB  - BACKGROUND: Glucocorticoid is widely used as an anti-inflammatory drug in various
      diseases however excess of it often causes cardiovascular complications. The
      present study was undertaken to understand the molecular mechanism of
      glucocorticoid-induced cardiac dysfunction. METHODS: Rats were treated daily with
      synthetic glucocorticoid, dexamethasone with or without mifepristone or losartan
      up to 15 days. Hemodynamic parameters were measured by PV-loop method using
      Millar's instrument. Cardiac remodelling, fibrosis and oxidative stress were
      monitored after 15 days. RESULTS: The systolic blood pressure was increased
      whereas the heart beat and cardiac output (n=6) were decreased by dexamethasone.
      Dexamethasone caused increase in the heart weight to body weight ratio (P<0.001,
      n=20), increased level of mRNA of atrial natriuretic peptide and an increased
      deposition of collagens in the extracellular matrix of the left ventricle which
      were inhibited by both mifepristone and losartan. The rate of oxygen consumption
      was decreased in association with increased levels of hypoxia inducible factor
      1alpha, lipid peroxidation (P<0.01, n=3) and superoxide dismutase activity
      (P<0.01, n=3) in dexamethasone treated rat heart. All these changes were reversed
      by mifepristone and losartan. CONCLUSIONS: The excess of glucocorticoid induces
      cardiac remodelling and pathophysiolgical changes of the myocardium via
      angiotensin II signalling pathway.

PMID- 19590190
TI  - DNA methylation of K(v)1.3 potassium channel gene promoter is associated with
      poorly differentiated breast adenocarcinoma.
AB  - BACKGROUND: DNA methylation is an important mechanism for gene silencing and has
      already been described for several genes in breast cancer. A previous
      immunohistochemistry study demonstrated a decrease of K(v)1.3 potassium channel
      expression in breast adenocarcinoma compared to normal breast tissue. METHODS:
      Methyl-specific PCR (MSP), immunohistochemistry and RNA extraction were performed
      on breast adenocarcinoma. MSP and DNA extraction were also performed on one
      breast carcinoma cell line and on primary culture normal cells. RESULTS: DNA
      methylation of K(v)1.3 gene promoter was observed in 42.3% of samples (22/52).
      The methylated status was associated with poorly differentiated tumors (p=0.04)
      and younger patients (p=0.048). Decreased K(v)1.3 expression was observed in
      grade III tumors, at both the mRNA and protein levels, while methylation
      increased in grade III tumors. Finally, K(v)1.3 gene promoter was methylated in
      the MCF-7 breast carcinoma cell line while promoter methylation was absent in
      primary culture of normal breast cells (HMEpC). CONCLUSION: We report, for the
      first time, the methylation of the K(v)1.3 gene promoter in breast
      adenocarcinoma. Our data suggest that DNA methylation is responsible for a
      decrease of K(v)1.3 gene expression in breast adenocarcinoma and is associated
      with poorly differentiated tumors and younger patients.

PMID- 19590191
TI  - Surveying the response of transport channels of intact RBC membranes upon AgNO3
      administration: an atomic force microscopy study.
AB  - BACKGROUND/AIMS: Cell membranes facilitate the transport of water, ions, and
      necessary nutrients by hosting a great variety of transport channels that have
      either a 'simple' pore-like structure or more complex architecture that is based
      on the utilization of specific receptors. The present study reveals the impact of
      AgNO3, a well-known inhibitor of water channel activity, on transport channels
      that emerge at the membrane of intact red blood cells (iRBCs). METHODS: Atomic
      force microscopy is employed to survey the morphological modification of all
      transport channels by directly comparing the respective images obtained on the
      exact same iRBCs prior to and after spraying the AgNO3 solution. RESULTS: Small
      pores of mean size 50 nm that were assigned to water channels, and extended
      orifices of mean size 300 nm that exhibit a neck-like extracellular segment were
      observed at the iRBC membrane. CONCLUSION: Our results reveal that AgNO3 exerts
      noticeable influence on all transport channels so that its selective water
      channel inhibitory action should be reconsidered. For low AgNO3 concentrations
      extended recovery of the small pore network was observed upon waiting, giving
      strong evidence that iRBCs have a recovery potential upon simply removing the
      inhibition cause without the need for specific reducing agents.

PMID- 19590192
TI  - Mammalian AT2 receptors expressed in Xenopus laevis oocytes couple to endogenous
      chloride channels and stimulate germinal vesicle break down.
AB  - BACKGROUND AND AIMS: A comparative analysis was performed of the properties of
      cloned AT1 and AT2 receptors and their ability to induce ion currents and oocyte
      maturation. METHODS: Frog oocytes were injected with cRNA that codes for rat AT1A
      and AT2 and bovine AT1 receptors and membrane currents were recorded by using the
      two-microelectrode voltage-clamp technique. Oocyte maturation was scored by
      observation of the germinal vesicle breakdown (GVBD). RESULTS: Xenopus oocytes
      expressing AT1 or AT2 generated oscillatory chloride currents by coupling to the
      diacylglycerol/inositol-3-phosphate (DAG/IP(3)) cascade. Ang II activation of
      collagenase-defolliculated oocytes expressing rat AT1A yielded larger chloride
      currents (9.2+/-3.4 A) than those generated by oocytes expressing bovine AT1
      (3.78+/-2.6 A). Oocytes expressing rat AT1A were recovered from desensitization
      after 0.5 h and completely after 10.5 h; whereas oocytes expressing bovine AT1
      receptors were unable to do so. Expression of rat AT2 generated smaller chloride
      currents (32-210 nA). Expression of AT2 receptors triggered GVBD whereas AT1 did
      not. The proportion of oocytes developing GVBD was greater for folliculated
      oocytes than for oocytes that were defolliculated. Furthermore, oocytes injected
      with AT2 secreted into the media, a heat-resistant factor(s) that stimulated GVBD
      of oocytes. This media elicited inward and outward membrane currents when applied
      to non-injected oocytes. CONCLUSION: Activation of AT1 and AT2 receptors couple
      to similar metabolic cascades in Xenopus laevis oocytes. However, the pathway
      activated by AT2 diverges to induce oocyte maturation.

PMID- 19590193
TI  - cAMP-dependent chloride conductance evokes ammonia-induced blebbing in the
      microglial cell line, BV-2.
AB  - Cell blebbing is a key feature in apoptosis. Because blebbing dynamically alters
      cell volume and regulatory volume changes have been linked to chloride (Cl)
      channels, we evaluated an association between blebbing and Cl channels activity.
      We used scanning electron microscopy, confocal laser microscopy, and cell sorting
      to quantify cell volume and blebbing and whole-cell recording to characterize Cl(
      ) currents. We found that blockade of Cl channel activity as well as inhibition
      of adenylyl cyclase or protein kinase A (PKA) activity suppressed ammonia-induced
      blebbing in the microglia cell line, BV-2. In further experiments, we elucidated
      the common mechanism of Cl channel activity and cyclic adenosine 3',5'
      monophosphate (cAMP)-dependent pathway on cell blebbing. These experiments
      indicated that perfusion of cells with cAMP or the catalytic subunit of PKA
      activated a Cl(-) current under normotonic conditions. The pharmacological
      profile (sensitivity to 5-nitro-2-(3-phenylpropylamino)benzoic acid [NPPB],
      flufenamic acid, and [(dihydroindenyl)oxy]alkanoic acid [DIOA]), outward
      rectification, and kinetic of the current were identical to the swelling
      activated Cl channel. Superfusion of cells with ammonia elicited an outwardly
      rectifying current sensitive to Cl channel blockers. We propose that ammonia
      induces a PKA-dependent phosphorylation of Cl channels. Localized influx of Cl(-)
      is followed by influx of water, required for bleb expansion.

PMID- 19590194
TI  - Therapeutic efficacy and safety of amitriptyline in patients with cystic
      fibrosis.
AB  - Amitriptyline, a blocker of acid sphingomyelinase and acid ceramidase,
      significantly reduces Pseudomonas aeruginosa lung infection in cystic fibrosis
      (CF) mice with concurrent increase of survival. Our aim was to establish whether
      amitriptyline is safe and effective in the treatment of CF patients. In a
      randomised, double-blinded, placebo-controlled, cross-over pilot study, 4 adult
      CF patients received 37.5 mg of amitriptyline or placebo twice daily for 14 days.
      Subsequently in a phase II study 19 adult CF patients were randomly allocated to
      three treatment groups receiving amitriptyline once daily for 28 days at doses of
      25 mg (n=7), 50 mg (n=8), or 75 mg (n=8) or placebo (n=13). The primary outcome
      was the difference of forced expiratory volume in 1 sec (FEV(1)) at day 14
      between amitriptyline and placebo. Primary endpoint measures improved
      significantly in three of four patients in the pilot study after amitriptyline
      treatment vs placebo (relative FEV(1): 14.7+/-5%; p = 0.006) and in the 25 mg
      treatment group of the phase II study (relative FEV(1): 4.0+/-7%; p = 0.048).
      Amitriptyline was well tolerated in both studies and 96% of the patients
      completed the studies. Amitriptyline as a novel therapeutic option in patients
      with CF is safe and seems to be efficacious.

PMID- 19590195
TI  - Cardiac myocytes derived from murine reprogrammed fibroblasts: intact hormonal
      regulation, cardiac ion channel expression and development of contractility.
AB  - AIMS: Induced pluripotent stem (iPS) cells have a developmental potential similar
      to that of blastocyst-derived embryonic stem (ES) cells and may serve as an
      autologous source of cells for tissue repair, in vitro disease modelling and
      toxicity assays. Here we aimed at generating iPS cell-derived cardiomyocytes
      (CMs) and comparing their molecular and functional characteristics with CMs
      derived from native murine ES cells. METHODS AND RESULTS: Beating cardiomyocytes
      were generated using a mass culture system from murine N10 and O9 iPS cells as
      well as R1 and D3 ES cells. Transcripts of the mesoderm specification factor T
      brachyury and non-atrial cardiac specific genes were expressed in differentiating
      iPS EBs. Using immunocytochemistry to determine the expression and intracellular
      organisation of cardiac specific structural proteins we demonstrate strong
      similarity between iPS-CMs and ES-CMs. In line with a previous study
      electrophysiological analyses showed that hormonal response to beta-adrenergic
      and muscarinic receptor stimulation was intact. Action potential (AP) recordings
      suggested that most iPS-CMs measured up to day 23 of differentiation are of
      ventricular-like type. Application of lidocaine, Cs+, SEA0400 and verapamil+
      nifedipine to plated iPS-EBs during multi-electrode array (MEA) measurements of
      extracellular field potentials and intracellular sharp electrode recordings of
      APs revealed the presence of I(Na), I(f), I(NCX), and I(CaL), respectively, and
      suggested their involvement in cardiac pacemaking, with I(CaL) being of major
      importance. Furthermore, iPS-CMs developed and conferred force to avitalized
      ventricular tissue that was responsive to beta-adrenergic stimulation.
      CONCLUSIONS: Our data demonstrate that the cardiogenic potential of iPS cells is
      comparable to that of ES cells and that iPS-CMs possess all fundamental
      functional elements of a typical cardiac cell, including spontaneous beating,
      hormonal regulation, cardiac ion channel expression and contractility. Therefore,
      iPS-CMs can be regarded as a potentially valuable source of cells for in vitro
      studies and cellular cardiomyoplasty.

PMID- 19590196
TI  - Developmental potential of the murine embryonic stem cells transplanted into the
      healthy rat brain--novel insights into tumorigenesis.
AB  - Although engraftment of undifferentiated pluripotent embryonic stem cells (ESCs)
      into the injured central nervous system (CNS) may lead to targeted cell
      replacement of lost/damaged cells, sustained proliferative activity combined with
      uncontrolled differentiation of implanted cells presents a risk of tumor
      formation. As tumorigenic potential is thought to be associated with pluripotency
      of embryonic stem cells, pre-differentiation may circumvent this problem.
      Recently, it has been demonstrated that tumorigenesis occurs despite pre
      differentiation if the neural precursor cells are implanted into the brain of a
      homologous animal (e.g., mouse to mouse). However, xenotransplantation (e.g.,
      mouse to rat) without pre-differentiation, lead to the development of healthy
      neuronal cells, in absence of tumor formation, suggesting that tumor-suppressive
      effects of host tissue on engrafted ESCs may play a role in transplant
      tumorigenesis. We critically investigated tumorigenesis and possible mechanisms
      of anticipated tumor-suppressive effect under conditions analogous to previously
      published studies. Xenotransplantation of D-3 murine ESCs into uninjured adult
      rat brains lacking any preliminary inflammatory potential was found to lead to
      tumor formation in 5 out of 8 of animals within 2 weeks postimplantation. Tumor
      suppressive effects, reflected by Erdo et. al could possibly be ascribed to
      immunomodulatory activity of macrophages scavenging the tumorigenic fraction of
      the implanted cells. The importance of number of engrafted cells, implantation
      site and immunosuppressive effects are discussed as possible variables
      determining tumorigenic outcome after ESC transplantation.

PMID- 19590197
TI  - Barbigerone, a natural isoflavone, induces apoptosis in murine lung-cancer cells
      via the mitochondrial apoptotic pathway.
AB  - Barbigerone is a naturally occurring isoflavone with antioxidant activity. In
      present study, we investigated the antitumor activity of barbigerone against
      murine lung cancer cells LL/2 and the possible mechanism in vitro. Our results
      showed that barbigerone inhibited LL/2 cells proliferation in a concentration-
      and time-dependent manner and caused apoptotic death of LL/2 cells. Barbigerone
      induced apoptosis was characterized by enhanced mitochondrial cytochrome c
      release, activation of caspase-3,-9, but not caspase-8. Exposure of LL/2 cells to
      barbigerone resulted in upregulation of Bcl-2-associated protein (Bax) and down
      regulation of Bcl-2. In addition, proliferation inhibitory effect of barbigerone
      was associated with decreased level of phosphorylated p42/44 mitogen-activated
      protein kinase (p42/44 MAPK) and phosphorylated Akt. Moreover, barbigerone
      exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, our
      results indicated that barbigerone can inhibit murine lung cancer cell
      proliferation by inducing apoptosis via mitochondrial apoptotic pathway and by
      decreasing phosphorylated p42/44 MAPK and Akt. Its potential to be a candidate of
      anti-cancer agent is worth being further investigated.

PMID- 19590198
TI  - Advanced oxidation protein products inhibit proliferation and differentiation of
      rat osteoblast-like cells via NF-kappaB pathway.
AB  - BACKGROUND/AIMS: Advanced oxidation protein products (AOPPs), a novel marker for
      oxidative protein damage, regulated cell behavior in many cell types. Although
      previous reports have revealed that oxidative stress resulted in an increased
      AOPPs content in cultured osteoblast-like cells, the effects of AOPPs on
      osteoblast-like cell function remain unclear. This study aimed to investigate the
      effect of AOPPs on the proliferation and differentiation of rat osteoblast-like
      (ROB) cells in vitro. METHODS: ROB cells isolated from calvarias of newborn rats
      were incubated with AOPPs-modified rat serum albumin (AOPPs-RSA) prepared in
      vitro by incubation of RSA with hypochlorous acid. Cell proliferation was
      evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide
      (MTT) assay. Alkaline phosphatase activity was measured. Expression of
      osteocalcin mRNA and protein were examined using reverse transcriptase-polymerase
      chain reaction and Western blot, respectively. Reactive oxygen species (ROS)
      generation was detected by flow cytometry and fluorescent microscope.
      Phosphorylation of nuclear factor (NF)- kappaB p65 subunit was detected by
      Western blot. RESULTS: Exposure of ROB cells to AOPPs-RSA significantly inhibited
      cell proliferation, decreased alkaline phosphatase activity, down-regulated the
      expression of osteocalcin mRNA and protein in both a concentration- and time
      dependent manner. AOPPs challenge induced ROS generation and NF-kappaB p65
      phosphorylation, which were inhibited by superoxide dismutase, catalase and NADPH
      oxidase inhibitors diphenyleneiodonium and apocynin. Furthermore, NF-kappaB
      inhibitor SN50 could reverse the AOPPs-induced inhibition of ROB cell
      proliferation and differentiation. CONCLUSION: These results suggest that AOPPs
      can inhibit proliferation and differentiation of ROB cells through ROS-dependent
      NF-kappaB pathway.

PMID- 19590199
TI  - Asymmetric dimethylarginine impairs glucose utilization via ROS/TLR4 pathway in
      adipocytes: an effect prevented by vitamin E.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), the inhibitor of nitric oxide
      synthase (NOS), has been reported to be associated with glucose metabolism, but
      its mechanisms remain unknown. METHODS: In 3T3-L1 adipocytes, we measured the
      effects of ADMA on glucose transport process under basal or insulin-induced
      condition, and examined the production of nitric oxide (NO), reactive oxygen
      species (ROS) and tumor necrosis factor alpha (TNF-alpha), and the expression of
      toll-like receptor 4 (TLR4). RESULTS: ADMA significantly impaired basal or
      insulin-stimulated 2-deoxy- [3H] glucose uptake, and decreased the expression of
      insulin receptor substrate-1 (IRS-1) and glucose transporter-4 (GLUT4).
      Phosphorylated protein of IRS-1 and translocation of GLUT4 with insulin
      stimulation were also inhibited by ADMA. NO decreased, while production of ROS
      and TNF-alpha, and expression of TLR4 increased after ADMA treatment. Vitamin E
      reduced the effects of ADMA on glucose transport system, and on NO, ROS and TLR4.
      Moreover, vitamin E decreased ADMA contents by up-regulating dimethylarginine
      dimethylaminohydrolase (DDAH) activity in adipocytes. Though L-arginine also
      increased NO level, but failed to reduce the effects of ADMA. CONCLUSION: ADMA
      significantly impairs both basal and insulin-stimulated glucose transport in
      adipocytes, which may relate to activation of the ROS/TLR4 pathway.

PMID- 19590200
TI  - Expression profiling of stationary and migratory intestinal epithelial cells
      after in vitro wounding: restitution is accompanied by cell differentiation.
AB  - Rapid repair by cell migration, a process called "restitution", is essential for
      wound healing of mucous epithelia. Here, an established in vitro model for
      restitution, i.e., migration of the non-transformed intestinal epithelial cell
      line IEC-18 after scratch wounding, was investigated. This cell line is also
      known for its retained differentiation potential. The aim of this study was to
      test by expression profiling whether the differentiation state is altered during
      restitution in vitro. Using a sensitive RT-PCR method a systematic analysis of
      separated stationary and migratory cells was performed 48 h after in vitro
      wounding. Most characteristically, the differentiation state was changed in
      migratory cells when compared with stationary cells. For example, migratory cells
      lost markers of terminal differentiation and changed to a phenotype that assists
      the process of restitution by up-regulating the expression of genes such as
      plasminogen activator inhibitor-1, transforming growth factor alpha, heparin
      binding EGF-like growth factor, alpha-smooth muscle actin, ornithine
      decarboxylase, and glyceraldehyde-3-phosphate dehydrogenase. However, there were
      no unequivocal signs of epithelial-mesenchymal transition (EMT) found in
      migratory cells.

PMID- 19590201
TI  - Education, occupation, and dementia: the Bavarian school sisters study.
AB  - BACKGROUND/AIMS: An inverse association of educational level with the occurrence
      of dementia has been repeatedly demonstrated. The mechanism of this relationship
      is not yet clear. Studies on populations with different educational and
      occupational levels but uniform living conditions throughout adult life may serve
      as a natural experiment and may help to rule out lifestyle and environmental
      factors as possible explanations. METHODS: We studied the relationship of
      education, occupational training, and appointment to a leading position with
      dementia in a cross-sectional study of older female members of a religious order.
      RESULTS: Out of 517 eligible sisters, 442 (85.5%) with an average of 54 years
      membership in the order participated in the study, among which 104 cases of
      dementia were identified. We found a strong association of low educational and
      occupational attainment with dementia. The increased risk of dementia was
      attributable to sisters being poorly educated (age-adjusted OR = 4.5; 95% CI: 2.0
      9.9), not having received any vocational training (OR = 9.1; 95% CI: 3.9-20.9),
      and never having been appointed to a leading position (OR = 3.7; 95% CI: 2.0
      7.0). CONCLUSION: In a setting which largely excludes the influence of lifestyle
      and environmental factors, we observed a strong association between educational
      variables and dementia. Our findings support the hypothesis of a reserve capacity
      against the consequences of brain diseases.

PMID- 19590202
TI  - Preoperative prediction of lymph node status in gastric cancer patients with the
      help of computer analysis.
AB  - INTRODUCTION: An optimal management of gastric cancer should be stage-oriented
      with the main criterion of lymph node status. Nodal status can be assessed
      preoperatively with modern radiological imaging techniques, sentinel node biopsy,
      molecular or genetic markers of tumor and computer analysis. The aim of this
      study was to evaluate the feasibility and accuracy in preoperative prediction of
      lymph node status with the help of computer analysis. METHODS: The computer model
      was constructed with data from patients with gastric cancer treated at the
      University Medical Centre Ljubljana between 1993 and 2003. Prediction of the
      computer model was then tested on 110 patients treated between 2004 and 2005 in
      the same manner as patients from the database. The goal of the study was to
      compare prediction for lymph node status in the control group by the computer
      program with real data collected after surgery. RESULTS: Accuracy of computerized
      preoperative predictions of N0/N1 status is 86% (sensitivity 91% and specificity
      79%) and of N1/N2 status is 89% (sensitivity 87% and specificity 90%).
      CONCLUSION: Results of accuracy of preoperative predictions of nodal status are
      very high and allow in each individual case to guide stage-appropriate therapy.
      Best applicability is obtained with implementation of this new approach with
      standard diagnostic methods.

PMID- 19590203
TI  - Pleomorphic liposarcoma of the axilla metastatic to the pancreas.

PMID- 19590204
TI  - Transcatheter arterial embolization for bleeding peptic ulcers: is the use of
      coils alone the best choice?

PMID- 19590206
TI  - Tailoring treatment for early gastric cancer after endoscopic resection using
      sentinel node navigation with infrared ray electronic endoscopy combined with
      indocyanine green injection.
AB  - BACKGROUND: This study evaluated the efficacy of sentinel node navigation surgery
      using infrared ray electronic endoscopy (IREE) combined with indocyanine green in
      patients after endoscopic treatments of early gastric cancer. METHODS: 14
      patients with early gastric cancer after endoscopic treatments were included.
      Each patient underwent sentinel node navigation surgery using IREE. Sentinel node
      detection rate, accuracy of sentinel node metastases and clinical efficacy
      including the presence or absence of recurrence were evaluated. RESULTS: The
      intraoperative sentinel node detection rate was 100% (14/14), and accuracy for
      sentinel node metastases was 93% (13/14). Based on the results of sentinel node
      mapping, 2 patients received standard gastrectomy with D2 lymphadenectomy, and
      the remaining 12 patients underwent limited surgery with lymphatic basin
      dissection. After median follow-up of 32 months, no patients had tumor
      recurrence. CONCLUSION: The validity of limited surgery based on sentinel node
      navigation for early gastric cancer remains unclear because the results of a well
      designed multicenter clinical trial of sentinel node mapping for gastric cancer
      have not yet been reported. However, this study suggests that sentinel node
      navigation surgery using IREE combined with indocyanine green is useful for early
      gastric cancer after endoscopic resection.

PMID- 19590205
TI  - A comprehensive review of evidence-based strategies to prevent and treat
      postoperative ileus.
AB  - BACKGROUND: Postoperative ileus (POI) is a common complication of abdominal and
      several other surgeries leading to increased hospital stay and healthcare costs.
      POI also contributes towards numerous postsurgical comorbidities including deep
      vein thrombosis and pneumonia. POI is characterized by bowel distention and lack
      of bowel sounds, flatus and bowel movements. The causative mechanism is not fully
      understood and may be multifactorial including disorganized electrical activity,
      activation of inflammatory mediators and the use of opioid analgesics. METHODS: A
      selective review of the literature pertaining to the prevention and treatment of
      adynamic ileus and POI was completed. More specifically we sought to evaluate
      RCTs, meta-analyses, consensus statements and articles providing graded evidence
      based data on POI prevention and treatment. RESULTS: Perioperative strategies
      employed to prevent or limit the duration of POI include avoidance of
      preoperative fasting and mechanical bowel preparation, use of epidural-local
      anesthetics, implementation of minimally-invasive surgical techniques, and
      modification of pain management strategies to limit opioid administration among
      others. CONCLUSION: Though many of these strategies have proven beneficial, no
      single approach has demonstrated the ability to prevent or treat POI. However,
      when these strategies are used in combination as part of a fast-track multimodal
      treatment plan, there is a significant decrease in time to return of normal bowel
      function and a shortened hospital stay. Additional studies are needed to make
      specific recommendations regarding which components of fast-track protocols are
      most beneficial.

PMID- 19590207
TI  - Loop colostomy with a suprafascial bridge device.
AB  - INTRODUCTION: The aim of this technique is to achieve a quick, efficient and easy
      to-perform as well as to reverse surgical procedure for patients requiring
      temporary deviation of stool transit, which can be carried out even by surgeons
      with little experience. METHODS: We describe our technique for loop colostomy
      over a subcutaneous plastic rod device placed not on the skin but on the
      superficial abdominal aponeurosis. RESULTS: Nineteen loop colostomies were
      performed using this technique, with no complications of either stoma formation
      or its subsequent function. The patient population consisted of 10 men and 9
      women (average age 64 years). Patients were all followed up for 24 months or
      until death. Six deaths occurred in patients operated for palliative purposes.
      CONCLUSIONS: This technique is not only very useful for patients in poor health
      who have undergone surgery due to intestinal blockage and need a quick surgical
      procedure to deal with an acute bowel disorder, but also in palliative
      situations.

PMID- 19590208
TI  - Inflammatory fibroid polyp causing intestinal obstruction following restorative
      proctocolectomy for ulcerative colitis.

PMID- 19590209
TI  - A primary splenic cyst in a 10-year-old boy.

PMID- 19590210
TI  - Massive cutaneous metastases in the lower part of the body of a patient with
      rectal cancer.

PMID- 19590211
TI  - Giant mesenteric lymphangioma.

PMID- 19590212
TI  - Preoperative radiotherapy has no value for patients with T2-3, N0 adenocarcinomas
      of the rectum.
AB  - BACKGROUND: Treatment of rectal cancer with preoperative radiotherapy followed by
      total mesorectal excision is nowadays the standard treatment. It reduces local
      recurrences and improves overall survival. However, in patients with T2-3, N0
      rectal cancer, the role of preoperative radiotherapy remains controversial. The
      aim of this study was to review the benefit of radiotherapy in T2 and T3, N0
      rectal cancer patients. METHODS: Between 1996 and 2003, 103 patients with T2-3,
      N0 rectal cancer were identified in our prospective database. This study
      evaluated time to local recurrence, distant metastases and overall survival.
      RESULTS: Median follow-up was 4.3 years. The 5-year local control rate was 94%.
      The 5-year overall survival was 65%. The 5-year disease-free survival rate was
      82%. Preoperative radiotherapy did not show any statistical differences.
      Abdominal perineal resection and T3 tumors negatively influenced overall survival
      (p = 0.02). Advanced age was of significant importance in overall survival.
      CONCLUSIONS: Preoperative radiotherapy does not seem to be of significant
      importance in patients with T2-3, N0 rectal cancer regarding local recurrence and
      survival. Since preoperative radiotherapy is associated with short- and long-term
      morbidity, patients with T2-3, N0 tumors should be identified and treated with
      surgery alone.

PMID- 19590214
TI  - Lower limb radiology of distal myopathy due to the S60F myotilin mutation.
AB  - Distal myopathies are a clinically and genetically heterogenous group of
      disorders in which the distal limb musculature is selectively or
      disproportionately affected. Precisely defining specific categories is a
      challenge because of overlapping clinical phenotypes, making it difficult to
      decide which of the many known causative genes to screen in individual cases. In
      this study we define the distinguishing magnetic resonance imaging findings in
      myotilin myopathy by studying 8 genealogically unrelated cases due to the same
      point mutation in TTID. Proximally, the vastii, biceps femoris and
      semimembranosus were involved with sparing of gracilis and sartorius. Distally,
      soleus, gastrocnemius, tibialis anterior, extensor hallicus and extensor
      digitorum were involved. This pattern contrasts with other distal myopathies and
      provides further support for the role of imaging in the clinical investigation of
      muscle disease.

PMID- 19590215
TI  - Interferon-beta(1b) treatment in neuromyelitis optica.
AB  - BACKGROUND: The effects of interferon-beta(1b) (IFN-beta(1b)) administration in
      multiple sclerosis (MS) patients have been confirmed, however, those in
      neuromyelitis optica (NMO) patients have not been shown. In this study, we
      assessed the effects of IFN-beta(1b) treatment on disease exacerbation and
      disability progression in MS or NMO patients. METHODS: We reviewed a series of
      104 consecutive patients with relapsing-remitting MS (RRMS) (69) or NMO (35)
      treated with IFN-beta(1b) in the MS clinical center of a national hospital in
      Japan. RESULTS: The relapse number in the RRMS patients significantly decreased
      within 1 year after IFN-beta(1b) treatment (p < 0.00001); however, that in the
      NMO patients did not show a significant decrease (p = 0.5601). The decrease in
      annualized relapse rates in each RRMS patient after treatment was significant (p
      < 0.01), but that in each NMO patient was not (p > 0.05). The change in Kurtzke's
      Expanded Disability Status Scale score 1 year after treatment was higher in the
      NMO patients than in the RRMS patients (p = 0.0225). CONCLUSION: In NMO patients,
      IFN-beta(1b) treatment was not effective in reducing the relapse number and the
      disability progression.

PMID- 19590216
TI  - Status epilepticus in stroke patients.
AB  - BACKGROUND: Status epilepticus (SE) is a life-threatening condition that occurs
      in only 1.5% of the overall stroke population but in more than 10% of patients
      with stroke-related seizures. This retrospective study compares the
      characteristics of stroke patients with SE to those with ordinary seizures (OS).
      PATIENTS AND METHODS: The demographic features, vascular risk factors, stroke
      type and etiology, stroke severity (according to the National Institute of Health
      Stroke scale) and disability (according to the modified Rankin scale), seizure
      type and onset, and post-ictal EEG findings were compared between 33 patients
      with SE and 288 with OS. SE was defined as a >30 min of either continuous seizure
      activity or multiple seizures without regaining consciousness. RESULTS: Patients
      with SE had more severe strokes and a worse outcome. Demographic features and
      stroke etiology were similar in both groups. Chronic obstructive pulmonary
      disease was only observed as a risk factor in patients with OS. There was a non
      statistical trend that SE occurred more frequently at stroke onset. Seizure
      recurrence was the same in both groups. Post-ictal EEG was always abnormal in the
      SE patients and normal in 30% of the OS group. CONCLUSIONS: SE occurs mainly in
      patients with a severe stroke and with severe disability. Patients with a severe
      stroke are probably more at risk of early-onset SE.

PMID- 19590217
TI  - Microsurgical technique of simultaneous pancreas/kidney transplantation in the
      rat: clinical experience and review of the literature.
AB  - BACKGROUND: For experimental basic research, standardized transplantation models
      reflecting technical and immunologic aspects are necessary. This article
      describes an experimental model of combined pancreas/kidney transplantation
      (PKTx) in detail. MATERIALS AND METHODS: Donor rats underwent en bloc
      pancreatectomy and nephrectomy. Revascularization was performed using the aorta
      with the superior mesenteric artery and the inferior vena cava with the portal
      vein. Exocrine drainage of the pancreas took place over a segment of the duodenum
      which was transplanted side-to-side to the jejunum. The kidney vessels were
      transplanted end-to-side. The ureter was anastomosed by patch technique.
      Postoperatively, serum parameters were monitored daily. Biopsies for
      histopathology were taken on days 5, 8 and 12. RESULTS: All 12 recipients
      survived the combined PKTx without serious surgical complications. One thrombosis
      of the portal vein led to organ failure. Blood glucose levels were normal by the
      3rd postoperative day. The transplanted duodenal segment showed slight villous
      atrophy, and the kidneys were well perfused without vascular complications. The
      anastomosis between ureter and bladder was leakproof. CONCLUSIONS: Excellent
      graft function and survival rates can be achieved due to simplified operation
      technique and short operation time. It may thus have high clinical relevance to
      immunologic issues within the scope of basic research.

PMID- 19590218
TI  - Evaluation of the effects of deep brain stimulation of the subthalamic nucleus
      and levodopa treatment on parkinsonian voice using perturbation, nonlinear
      dynamic, and perceptual analysis.
AB  - BACKGROUND/AIMS: To quantify aperiodic phonation, nonlinear dynamic methods of
      acoustic voice analysis, such as correlation dimension, have been shown to be
      useful. The purpose of this study is to evaluate the validity of nonlinear
      dynamic analysis as a voice analysis tool for the effects of deep brain
      stimulation (DBS) and levodopa on patients with Parkinson's disease (PD).
      METHODS: In this study, the effects of DBS and levodopa treatment on patients
      with PD were measured using perturbation, nonlinear dynamic, and perceptual
      analysis. Nineteen PD patients that received bilateral (n = 9), left (n = 7), or
      right (n = 3) DBS performed sustained vowel phonations, which were recorded
      before and after medication with the stimulator off and on. Recordings were also
      taken of 10 PD patients who did not receive DBS surgery before and after
      medication to provide a baseline. RESULTS: A mixed two-way ANOVA (surgery,
      medication) generated significant positive treatment effects of DBS only in mean
      log-transformed D2, which was supported by mean log-transformed shimmer, vF0
      (variability in fundamental frequency), and vAm (peak-to-peak amplitude
      variation). CONCLUSION: These findings may indicate the validity of nonlinear
      dynamic analysis as a complement to perceptual analysis in clinical PD voice
      studies.

PMID- 19590219
TI  - The use of biofeedback in the treatment of chronic dysphagia in stroke patients.
AB  - OBJECTIVE: To evaluate the efficacy of the use of surface electromyographic
      feedback in the treatment of stroke patients with chronic dysphagia. PATIENTS AND
      METHODS: Data of 11 consecutive patients with chronic dysphagia after stroke were
      analyzed. Our patients were treated for dysphagia with surface electromyography
      as biofeedback as adjunct to normal exercises. All patients suffered from
      dysphagia after stroke. The average time after onset was 31.1 months. All
      patients had been previously treated by speech therapists without success.
      Functional swallowing was estimated using the Functional Oral Intake Scale
      (FOIS). At the start of the treatment 8 patients were tube dependent (FOIS < or =
      4). Three patients were on an oral diet, but with restrictions (FOIS > or = 5).
      RESULTS: The patients were treated on average seven 7 times. The time between the
      first and last treatment session was on average 76.1 days (SD +/- 44.0; range =
      29-168). Before treatment the average FOIS was 2.6 (SD +/-2.3) and after
      treatment 5.6 (SD +/-1.6). The median scores improved from 1 to 6, showing a
      significant and clinically relevant improvement (z = -2.820: p < 0.01) in
      swallowing function. In 6 of initially 8 patients with percutaneous enteral
      gastrostomy tubes, the feeding tube could be removed after treatment. CONCLUSION:
      Our data suggest that the use of surface electromyography as biofeedback in the
      treatment of chronic dysphagia after stroke could be an effective adjunct to
      standard therapy for swallowing disorders in 11 patients.

PMID- 19590220
TI  - Correlation between psychometric tests and mismatch negativity in preschool
      children.
AB  - The objective was to determine whether mismatch negativity (MMN) is suitable to
      supplement subjective psychometric subtests of central hearing. We assessed 13
      healthy children and 32 children with central auditory processing disorder
      (CAPD). Three different types of sound deviants were presented in a multi-deviant
      MMN design. At group level, the incidence of MMN was always higher in clinically
      diagnosed controls. Children with better results in the subtest Auditory Memory
      Span had a higher incidence of MMN. The controls also had peak latencies that
      occurred significantly earlier in frontal, central and temporal electrode sites.
      The area under the curve (AUC) displayed an asymmetric distribution in CAPD
      children, who tended to have a left-hemispheric dominance. AUC, peak latency, and
      the incidence of MMN reflected the discriminative ability of CAPD children.
      Hence, these characteristics could be used for investigating children with
      deficits in central hearing and can supplement psychometric tests.

PMID- 19590221
TI  - Perturbation measures of voice: a comparative study between Multi-Dimensional
      Voice Program and Praat.
AB  - BACKGROUND/AIMS: Frequency and amplitude perturbations are inherent in voice
      acoustic signals. The assessment of voice perturbation is influenced by several
      factors, including the type of recording equipment used and the measurement
      extraction algorithm applied. In the present study, perturbation measures
      provided by two computer systems (a purpose-built professional voice analysis
      apparatus and a personal computer-based system for acoustic voice assessment) and
      two computer programs (Multi-Dimensional Voice Program and Praat) were compared.
      METHODS: Correlations and inferential statistics for seven perturbation measures
      (absolute jitter, percent jitter, relative average perturbation, pitch
      perturbation quotient, shimmer in decibels, percent shimmer, and amplitude
      perturbation quotient) in 50 subjects with various voice disorders are presented.
      RESULTS: Results indicate statistically significant differences between the two
      systems and programs, with the Multi-Dimensional Voice Program yielding
      consistently higher measures than Praat. Furthermore, correlation analyses show
      weak to moderate proportional relationships between the two systems and weak to
      strong proportional relationships between the two programs. CONCLUSION: Based on
      the literature and the proportional relationships and differences between the two
      systems and programs under consideration in this study, one can state that one
      can hardly compare frequency perturbation outcomes across systems and programs
      and amplitude perturbation outcomes across systems.

PMID- 19590223
TI  - Segmental duration in Parkinsonian French speech.
AB  - OBJECTIVES: The present study had 2 main objectives: (1) examine the effect of
      Parkinson's disease (PD) on vowel and consonant duration in French read speech
      and (2) investigate whether the durational contrasts of consonants and vowels are
      maintained or compromised. RESULTS: The data indicated that the consonant
      durations were shortened in Parkinsonian speech (PS), compared to control speech
      (CS). However, this shortening was consonant dependent: unvoiced occlusives and
      fricatives were significantly shortened compared to other consonant categories.
      All vowels were slightly longer in PS than in CS, however, the observed
      differences were below the level of significance. Despite significant shortening
      of some consonant categories, the general pattern of intrinsic duration was
      maintained in PS. There was slightly less agreement for vowels with the normal
      contrast of intrinsic durations, possibly because vowel durational contrasts are
      more sensitive to PD disorders. CONCLUSION: Most PD patients tended to maintain
      the intrinsic duration contrasts of both vowels and consonants, suggesting that
      low-level articulatory constraints operate in a similar way and with the same
      weight in PS and CS.

PMID- 19590222
TI  - A comparison of the effects of Voice Massage and voice hygiene lecture on self
      reported vocal well-being and acoustic and perceptual speech parameters in female
      teachers.
AB  - This study compared the effects of Voice Massage (VM) and a voice hygiene lecture
      (VHL) on 60 female teachers. VM is a Finnish massage method which treats muscles
      related to voice production. All subjects attended the VHL (3 h). Half of them
      were randomly assigned to the VM group, the other half received only VHL. VM was
      given 5 times in 1-hour sessions at intervals of 1-2 weeks. At the beginning and
      end of the autumn school term, before and after a working day, (1) a 1-min
      reading sample was recorded at both the subject's habitual loudness and loudly,
      (2) a prolonged phonation on [a:] was recorded at habitual speaking pitch and (3)
      a questionnaire on voice quality, ease or difficulty of phonation, and tiredness
      of the throat was completed. The reading samples were analysed for the
      fundamental frequency (F0), equivalent sound level (Leq) and alpha-ratio [Leq (1
      5 kHz)-Leq (50-1,000 Hz)]. The vowel samples were analysed for the F0 and Leq, as
      well as for jitter and shimmer. The reading samples were also evaluated
      perceptually by 3 speech trainers. The mean F0 and difficulty of phonation
      increased from the beginning to the end of the term in the VHL group (p = 0.026,
      p = 0.007, respectively). In the VM group, the perceived firmness of loud reading
      decreased (p = 0.026). The results suggest that VM may help in sustaining vocal
      well-being during a school term.

PMID- 19590224
TI  - Ultrasonographic evidence that bedrest after embryo transfer is useless.
AB  - BACKGROUND: To demonstrate the effect of immediate ambulation after embryo
      transfer on the intrauterine location of the transfer content. METHODS:
      Prospective observational randomized controlled study. RESULTS: Fifty-seven
      patients (47.5%) had one air bubble at transfer and after 15 min change in
      position: group A (bedrest) 2.69 mm, group B (immediate ambulation) 2.00 mm (p =
      0.511). The distance from the fundus declined by 26% in group A and 15% in group
      B (p = 0.229). Twenty-eight patients (23.3%) had two air bubbles at transfer and
      after 15 min: average change in position of the first air bubble: group A 3.07
      mm, group B 1.80 mm (p = 0.282); average change in position of the second air
      bubble: group A 2.69 mm, group B 1.80 mm (p = 0.450). The distance from the
      fundus for the first air bubble declined by 2% in group A and 18% in group B (p =
      0.593) and for the second air bubble by 22% in group A and 15% in group B (p =
      0.711). CONCLUSIONS: This study demonstrates that the transfer content is not
      affected by the immediate ambulation after transfer, illustrating why there is no
      rationale for bedrest after transfer.

PMID- 19590225
TI  - Ultra-minilaparotomy myomectomy: a minimally invasive surgical approach for the
      treatment of large uterine myomas.
AB  - BACKGROUND: In recent years, a growing number of more conservative methods for
      the treatment of uterine myomas has been reported. However, only a small number
      of techniques is used for the treatment of large myomas. AIMS: In the present
      retrospective study, we report our experience with a group of patients who
      consecutively underwent ultra-minilaparotomy myomectomy for single or multiple
      large myomas, with diameter greater than 5 cm, with emphasis on the safety and
      efficacy of this procedure. METHODS: Forty-one women underwent an ultra
      minilaparotomy myomectomy that involved a <4 cm transverse skin incision, with or
      without laparoscopic assistance. RESULTS: Mean operating time was 92.4 min, the
      mean hemoglobin decline was 2.0 g/dl and the mean hematocrit decline was 5.7%.
      The mean time to discharge was 84.3 h. No patient underwent a second surgery for
      early postoperative complications. Postoperative fever occurred in 4 patients,
      especially in patients who underwent ultra-minilaparotomy without assisted
      laparoscopy. There were two cases of severe anemia with recourse to blood
      transfusion. CONCLUSION: The results of this study suggest that ultra
      minilaparotomy myomectomy with or without laparoscopic assistance might represent
      a safe and effective minimally invasive alternative to standard open myomectomy
      in the treatment of large myomas.

PMID- 19590227
TI  - First report of genotype e of hepatitis B virus in an Indian population.
AB  - Twenty-one hepatitis B virus (HBV) isolates from the state of Haryana (North
      India) were studied for genotype, subgenotype, serotype distribution and precore
      mutations. Assays of alanine aminotransminase (ALT) and HBeAg were performed on
      all samples. Genotypes, subgenotypes and serotypes were determined by
      amplification of pre-S1/S2 regions followed by RFLP and also by phylogenetic
      analysis of amplified products. Mutations were studied by amplification and
      sequencing of the precore region. Twenty-four percent of the samples had high ALT
      levels and 90% were HBeAg negative. It was observed that 90% of the samples were
      HBV D genotype, (subgenotype D1, serotype ayw2), 5% HBV A genotype (subgenotype
      A1, serotype adw2), and the remaining 5% were HBV E genotype (serotype ayw4). The
      subgenotype A1 was quite similar to the South African isolates. Phylogenetic
      analysis of the HBV isolates, based on the pre-S1/S2 gene sequences, confirmed
      genotype E. Amplification and sequencing of the precore region showed 1762(A-T)
      and 1764(G-A) mutations in 38 and 15% of the samples, respectively. 1809(T) was
      observed in 5% of the cases under study. This is the first report of the genotype
      E of hepatitis B virus in the Indian population. Efforts are underway to amplify
      and sequence the full length of this genotype E isolate.

PMID- 19590226
TI  - Molecular characterization and pathogenicity of infectious bronchitis
      coronaviruses: complicated evolution and epidemiology in china caused by
      cocirculation of multiple types of infectious bronchitis coronaviruses.
AB  - OBJECTIVE: To monitor and study the molecular epidemiology, evolution and
      pathogenicity of infectious bronchitis viruses (IBVs) in China in recent years
      and further our knowledge of the evolution of IBVs. METHODS: Thirty-seven IBV
      isolates were isolated from commercial chickens in China. The isolates were
      characterized by RT-PCR, sequencing, typing and analyzing the entire S1 gene. In
      addition, 4 selected IBV isolates were used to experimentally infect the specific
      pathogen-free chickens to study their pathogenicity. RESULTS: Three types of IBV
      have been cocirculating in chicken flocks in China in recent years. Unique
      insertions and deletions in S1 protein regions were identified among different
      types of IBV. Moreover, a new IBV strain was isolated and identified in a layer
      hen. S1 gene analysis showed that a recombination event had occurred in the
      virus's evolutionary process. In addition, experimental infection has shown that
      IBV isolates have been nephropathogenic in China in recent years. CONCLUSION:
      Mutations, insertions, deletions and recombination of the S1 protein gene
      contribute to the genetic diversity of IBV in China. Cocirculation of multiple
      types of IBV in field conditions in China renders its epidemiology and evolution
      very complicated, indicating the necessity for development of new vaccines or
      vaccine strategies.

PMID- 19590228
TI  - Impact of anemia on aortic pulse wave velocity in hemodialysis patients.
AB  - BACKGROUND: Recent studies indicate an increased mortality of anemic patients
      with renal failure when near-normal hemoglobin levels are aimed for by treatment
      with erythropoiesis stimulating agents. Aortic pulse wave velocity (aPWV) is a
      strong predictor of all-cause and cardiovascular mortality in patients with end
      stage renal disease. The relationships between aPWV, hemoglobin levels and
      erythropoiesis stimulating agent dosage have not been evaluated to date. METHODS:
      In 75 patients, aPWV was measured by applanation tonometry. Associations of aPWV
      and a broad range of clinical, laboratory and therapeutic parameters were
      determined by stepwise linear regression analysis. RESULTS: aPWV was positively
      correlated to age (r = 0.55, p < 0.001), whereas the association with hemoglobin
      was significant, but negative (r = -0.31, p = 0.01). Multivariate analysis
      determined age (beta = 0.513, p < 0.001), mean blood pressure (beta = 0.255, p =
      0.01), the presence of heart failure (beta = 0.188, p = 0.03), hemoglobin (beta =
      -0.226, p = 0.01), daily calcium load (beta = -0.230, p = 0.01) and the presence
      of diabetes mellitus (beta = 0.179, p = 0.04) to have a significant and
      independent influence on aPWV. CONCLUSIONS: This study demonstrates that in
      hemodialysis patients, aPWV is significantly but negatively associated with the
      serum hemoglobin concentration, even after multiple adjustments for other
      covariates.

PMID- 19590229
TI  - Transplant glomerulopathy: morphology, associations and mechanism.
AB  - Transplant glomerulopathy (TG) is a lesion with specific morphology and strong
      evidence of an immune mechanism. The incidence of TG is approximately 20% by 5
      years after transplantation. TG is characterized by proteinuria, hypertension and
      declining graft function. Appearances on light microscopy include thickened
      capillary walls and double contours, with reduplication or lamination of the
      glomerular basement membrane on electron microscopy. TG is associated with acute
      rejection, the antibody status before transplantation and de novo HLA antibodies.
      HLA class II and/or donor-specific antibodies incur additional risks.
      Desensitization protocols do not always prevent the development of TG in highly
      sensitized individuals. Associations between TG, past or current C4d and the
      presence of alloantibodies are recognised, however, C4d in the peri-tubular
      capillaries or glomeruli is not a prerequisite at the time of diagnosis. Clinical
      observation and animal models suggest that TG arises as a consequence of chronic
      endothelial cell (EC) injury by the humoral arm of the immune system. In some
      cases, this follows a period of EC accommodation after an episode of acute
      injury. Proposed treatments include augmentation of background immunosuppression,
      and trials of monoclonal therapies targeted at CD20-positive B cells are
      underway.

PMID- 19590230
TI  - Risk factors for development of microalbuminuria in diabetic and nondiabetic
      normoalbuminuric hypertensives with high or very high cardiovascular risk - a
      twelve-month follow-up study.
AB  - AIMS: To investigate risk factors for progression to microalbuminuria in
      normoalbuminuric hypertensive patients. METHODS: In a longitudinal study, 173
      previously treated normoalbuminuric hypertensive patients with high
      cardiovascular risk (70% diabetics) were evaluated at study entry and after 12
      months. Levels of urinary albumin excretion (UAE; study entry and end of study)
      were compared between patients remaining normoalbuminuric (RNA) and progressors
      to non-normoalbuminuric (NNA) levels. RESULTS: Out of 173 patients (59 +/- 13
      years), 12% evolved to NNA levels. At baseline, NNA and RNA groups did not differ
      in age, sex, diabetes, lipids, blood pressure (BP), drug therapy, or glomerular
      filtration rate. In comparison with RNA patients, the NNA group showed higher
      hypertension duration, greater UAE and percentage of patients with UAE >or=10
      mg/g creatinine (76.2 vs. 45.4%) at study entry and higher BP levels (158/92 +/-
      25/10 vs. 143/83 +/- 20/12 mm Hg) at study end (all p < 0.05). Logistic
      regression analysis identified absolute UAE values at study entry and study end
      variation of BP and cholesterol as independent contributors to the increase in
      the log odds of developing microalbuminuria. CONCLUSIONS: Normoalbuminuric
      hypertensives with UAE within the upper two thirds of normal range are 3 times as
      likely to develop microalbuminuria after 1 year. A poor BP and lipid control are
      also associated with increased risk of microalbuminuria.

PMID- 19590231
TI  - Influence of obesity on progression of non-diabetic chronic kidney disease: a
      retrospective cohort study.
AB  - BACKGROUND: There is increasing awareness of the impact of obesity on chronic
      diseases including chronic kidney disease (CKD). Until recently, a limited number
      of epidemiologic studies have examined the association between obesity and CKD.
      We conducted a retrospective cohort study to evaluate whether obesity impacts on
      the rate of non-diabetic CKD progression. METHODS: The medical records of 125 non
      diabetic CKD patients in the Sheffield Kidney Institute, Sheffield, UK, who have
      been followed-up for around 10 years, were reviewed. Various socio-demographic,
      clinical and biochemical parameters were retrospectively collected from the
      patients' database. Participants were categorized into normal weight, overweight
      and obese groups. Multivariate regression analysis was used for modelling with
      estimated glomerular filtration rate (eGFR) reduction per year as the dependent
      variable to evaluate the impact of obesity (BMI) on CKD progression. RESULTS:
      Patients studied were mostly CKD stage 3 with a mean GFR of 36.2 ml/min/1.73 m(2)
      for the control group and 44.3 ml/min/1.73 m(2) for those who were overweight or
      obese. Baseline diastolic and mean arterial blood pressure were significantly
      higher in overweight than normal weight CKD patients (p = 0.009 and p = 0.014
      respectively). On follow-up, systolic, diastolic and mean arterial blood pressure
      were significantly higher in overweight (p = 0.03, p = 0.005 and p = 0.003,
      respectively) and obese (p = 0.008, p = 0.022 and p = 0.003, respectively)
      compared to normal weight CKD patients. Mean follow-up triglycerides level was
      significantly higher in obese than normal weight patients (p = 0.042). The
      frequency of CKD progression based on eGFR fall per year (>1 ml/min/1.73
      m(2)/year) was 62.5% in overweight and 79.5% in obese compared to 44.7% in normal
      weight CKD patients (p = 0.007). However, no significant difference in the rate
      of progression (fall of eGFR ml/min/1.73 m(2)/year) was observed between the
      three groups. On multivariate regression analysis, adjusted for other covariates
      (age, BP and proteinuria), baseline BMI was an independent predictor of CKD
      progression (fall in eGFR, ml/min/1.73 m(2)/year) (R(2) = 0.122 and p < 0.001).
      Percentage changes in BMI over the observation period did not affect the rate of
      eGFR decline. Young age also predicted a faster CKD progression. CONCLUSIONS:
      Baseline BMI and young age are strongly and independently associated with faster
      CKD progression based on the annual rate of eGFR fall. Prospective studies to
      investigate the relationship between BMI and CKD and its complications are
      warranted.

PMID- 19590232
TI  - Adiponectin in children on peritoneal dialysis: relationship to insulin
      resistance and nutritional status.
AB  - AIM: To study whether adiponectin and resistin serum concentrations in children
      on peritoneal dialysis (PD) were related to insulin resistance (IR) and
      anthropometric parameters of nutritional status, 11 PD patients, 9 chronic kidney
      disease (CKD) patients and 10 healthy children were studied. METHODS: Glucose and
      insulin were measured during the oral glucose tolerance test. Levels of
      adiponectin and resistin were evaluated by ELISA, insulin by RIA. RESULTS: In CKD
      patients, higher homeostasis model assessment-insulin resistance (HOMA-IR),
      fasting and 2-hour serum insulin levels were shown compared to control and to PD
      patients. Body mass index (BMI) and body fat content were severely decreased
      while serum adiponectin levels were significantly higher in PD patients relative
      to controls. No differences among groups were shown in resistin levels. On
      regression modeling, inverse independent associations were observed between
      adiponectin with percentile BMI, weight and height z-score, and with body fat
      content. In contrast, no relationship was found between adiponectin and IR
      parameters. In multiple regression analysis, adiponectin was negatively
      correlated with BMI. A negative association of adiponectin and resistin with
      glomerular filtration rate was also shown. CONCLUSION: A role for adiponectin in
      terms of its association with clinical wasting parameters in PD pediatric
      patients might be suggested.

PMID- 19590233
TI  - Interdialytic weight gain in diabetic haemodialysis patients and diabetic control
      as assessed by glycated haemoglobin.
AB  - BACKGROUND: Cardiovascular morbidity and mortality is increased in diabetic
      haemodialysis patients. Diabetic subjects may suffer greater thirst and thereby
      be predisposed to increased interdialytic weight gains and hypertension. METHODS:
      175 established adult diabetic haemodialysis patients attending outpatient
      haemodialysis thrice weekly were audited during a 1-week interval. RESULTS:
      Despite fewer patients prescribed antihypertensive medications (46%), the mean
      pre-dialysis systolic blood pressure was lowest in those patients with the lowest
      HbA1c values (<or=6%; 146 +/- 27 mm Hg), versus 154 +/- 25 mm Hg for the highest
      group, with a HbA1c of >8%, of whom 70% were prescribed antihypertensive
      medications (p < 0.05). Both absolute and percentage interdialytic weight gain
      was lowest in the group with the best diabetic control: 2.0 +/- 1 kg and 2.76 +/-
      1.5% versus 2.5 +/- 1.1 kg and 3.3 +/- 1.3%, respectively (p < 0.05).
      CONCLUSIONS: Poor diabetic control may increase thirst and salt intake, leading
      to increased interdialytic weight gains, associated with systolic hypertension,
      and as such, diabetic control is an important facet in the management of the
      diabetic haemodialysis patient.

PMID- 19590235
TI  - Association of secondary hyperparathyroidism with CKD progression, health care
      costs and survival in diabetic predialysis CKD patients.
AB  - BACKGROUND/AIMS: The objective of this study was to examine health care costs and
      utilization and the risks of dialysis or mortality among diabetic predialysis
      chronic kidney disease (CKD) patients with and without secondary
      hyperparathyroidism (SHPT). METHODS: This retrospective, matched cohort study
      examined insurance claims from 703 adult diabetic predialysis CKD patients with
      and without SHPT during a 72-month follow-up period. Annualized estimates of
      health care service utilization, costs and disease progression to dialysis or
      death following index CKD diagnosis were compared. RESULTS: Preindex (baseline)
      characteristics were similar between the cohorts. Postindex numbers of
      prescription utilization, outpatient service utilization and hospitalizations
      were all higher (p < 0.0001) in diabetic CKD patients with SHPT compared to those
      without SPHT in both unadjusted and adjusted analyses even after multivariate
      adjustment for known confounders. The rate of progression to dialysis or death
      was higher for diabetic CKD patients with SHPT compared to those without SPHT.
      Those with SHPT were at higher risk of requiring dialysis treatment [hazard ratio
      (HR) = 6.7; 95% confidence interval (CI) = 4.3-10.6] and death (HR = 2.3; 95% CI
      = 1.1-4.9) compared to those without SHPT. CONCLUSION: In diabetic predialysis
      CKD patients, the presence of SHPT is associated with significantly greater
      health care resource utilization and costs, and a faster rate of disease
      progression.

PMID- 19590234
TI  - Increased iron requirement in hemodialysis patients on antiplatelet agents or
      warfarin.
AB  - BACKGROUND/AIMS: Many hemodialysis patients receive antiplatelet therapy or
      warfarin; however, little is known about the effect of this on iron requirements.
      Given the association of antiplatelet therapy with bleeding we hypothesized that
      there should be a greater need for iron in such patients, which we tested in this
      study. METHODS: Retrospective 1-year cohort study of 205 chronic hemodialysis
      patients. The primary outcome variable was total iron dose, which was analyzed
      according to antiplatelet/warfarin use. Data were also collected on potential
      confounders, allowing for both unadjusted and adjusted (multiple regression)
      analysis. RESULTS: 97/205 patients received antiplatelet/warfarin therapy. This
      group was older, with a higher incidence of macrovascular disease and diabetes
      and a higher median C-reactive protein (6.0 vs. 3.75 mg/l). Overall, median iron
      requirement was 1,300 mg/year. In a multiple regression analysis,
      antiplatelet/warfarin use was associated with an additional iron requirement of
      703 mg (95% confidence interval 188-1,220 mg), with the strongest effect observed
      in patients with normal inflammatory markers. CONCLUSION: We found a high
      requirement for iron in patients receiving antiplatelet agents/warfarin. We argue
      that the most likely mechanism for this association is chronic, low-grade blood
      loss, although further study is required before causality can be established.

PMID- 19590236
TI  - Toll-like receptors and renal disease.
AB  - Toll-like receptors (TLRs) play a central role in the response of both the innate
      and the adaptive immune system to microbial ligands. There is also evidence that
      they are stimulated by endogenous ligands. In this review, I discuss evidence
      that they are important in renal disease. This discussion considers the role of
      both endogenous and microbial ligands, and also the contribution of TLRs present
      on leucocytes and on intrinsic renal cells. There is strong evidence of a role
      for TLR2 and TLR4 in renal ischaemia-reperfusion injury, with the effects
      probably mediated by endogenous ligands. In systemic lupus erythematosus,
      stimulation of TLR7 and TLR9 by host-derived nucleic acids is important. TLR7
      stimulation exacerbates disease, but the role of TLR9 is complex. I also discuss
      evidence that they are important in other forms of glomerulonephritis, with
      evidence derived mainly from experimental models in which exogenous ligands have
      been administered.

PMID- 19590237
TI  - The importance of cellular VEGF bioactivity in the development of glomerular
      disease.
AB  - The bioactivity of glomerular VEGF (or activity of available VEGF) is critical to
      the physiological maintenance of the glomerular filtration barrier. Disturbances
      in glomerular VEGF expression have been linked to numerous glomerulopathies,
      highlighting its importance in disease progression within the kidney. However,
      the changes in expression are not consistent between conditions; enhanced
      expression sometimes appears to have a renoprotective effect, yet at other times
      it appears destructive. Also, the level of expression can change with the
      progression of disease. This review focuses on how other cellular factors, such
      as TGF-beta and nitric oxide, work in concert to affect the bioactivity, which is
      not necessarily the same as the expression of VEGF, in different glomerulopathies
      and attempts to explain some of the paradoxes between glomerulopathies. In
      conclusion, the bioactivity of glomerular VEGF is regulated by many factors that
      are themselves moderated by changes in the local glomerular environment, such as
      mechanical strain and hyperglycaemia. Thus, to understand VEGF signalling in
      glomerular disease progression, we must examine it in the context of other
      appropriate cellular factors.

PMID- 19590238
TI  - Y-box protein 1 stimulates mesangial cell proliferation via activation of ERK1/2.
AB  - AIMS: To investigate the effects of Y-box protein 1 (YB-1) on the mitogen
      activated protein kinase pathway to ascertain which signaling pathway is involved
      in YB-1-induced mesangial cell (MC) proliferation. METHODS: The rat MC line HBZY
      1 was transfected with pcDNA3.1-YB-1. Cell proliferation was determined by
      [(3)H]thymidine incorporation, cell counting and cell-cycle analysis. The
      expression of cyclins was examined by real-time RT-PCR and immunoblotting
      analysis. Phosphorylation of c-Raf, MEK1/2, and ERK1/2 was detected by
      immunoblotting analysis. RESULTS: MCs transfected with YB-1 showed an increased
      DNA synthesis and number of cells in the S and G2 phases of the cell cycle. The
      expression of cyclins (cyclin A2, cyclin D1, cyclin E and p27) was increased,
      while p21 levels were decreased. The expression levels of phosphorylated c-Raf
      kinase, MEK1/2 and the ERK1/2 proteins were elevated in MCs transfected with YB
      1. YB-1-stimulated cell proliferation was blocked by U0126, a specific inhibitor
      of ERK1/2. ERK1/2 regulated YB-1 expression in MCs stimulated with TGF-beta, an
      effect that was inhibited by U0126. CONCLUSIONS: YB-1 has an apparent stimulatory
      effect on c-Raf, MEK1/2, ERK1/2 and cell-cycle progression in MCs, after which
      activated ERK1/2 goes on to upregulate YB-1 expression and augment the
      proliferative effect of YB-1.

PMID- 19590239
TI  - Aldosterone induces apoptosis in rat podocytes: role of PI3-K/Akt and p38MAPK
      signaling pathways.
AB  - BACKGROUND: Podocytes play a critical role in the pathogenesis of
      glomerulosclerosis. Increasing evidence suggests that aldosterone (ALD) is
      involved in the initiation and progression of glomerular damage. It is, however,
      unknown whether there is a direct injurious effect of ALD on podocytes.
      Therefore, in the present study, we evaluated the effect of ALD on podocyte
      apoptosis and studied the role of phosphatidylinositol 3-kinase/Akt (PI3-K/Akt)
      and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways in this
      process. METHODS: Podocytes were incubated in media containing either buffer or
      increasing concentrations of ALD (10(-9) approximately 10(-5)M) for variable time
      periods. The cells were also treated with either wortmannin (inhibitor of PI3-K,
      100 nM), SB202190 (SB20, inhibitor of p38MAPK, 10 microM) or buffer. All
      treatments were performed with or without ALD (10(-7)M) for 24 h. At the end of
      the incubation period, apoptosis was evaluated by cell nucleus staining and flow
      cytometric analyses. Activation of PI3-K/Akt and p38MAPK phosphorylation of
      cultured rat podocytes was evaluated by performing Akt kinase assay and Western
      blot, respectively. RESULTS: Apoptosis of cultured rat podocytes was induced by
      ALD in a dose- and time-dependent manner. ALD inhibited the activity of PI3-K/Akt
      and increased the activation of p38MAPK. PI3-K/Akt activity was further inhibited
      by the addition of wortmannin to the cells in the presence of ALD. This was
      accompanied by a significant increase in apoptosis. ALD-induced p38MAPK
      phosphorylation and apoptosis were inhibited when the cells were pretreated with
      SB20. Furthermore, treatment with spironolactone not only attenuated the
      proapoptotic effect of ALD, but also significantly reversed its effects on PI3
      K/Akt and p38MAPK signaling pathways. CONCLUSION: ALD induces apoptosis in rat
      podocytes through inhibition of PI3-K/Akt and stimulation of p38 MAPK signaling
      pathways. Spironolactone attenuates ALD-induced podocyte apoptosis, thereby
      positioning this compound as a potential promising target of intervention in
      human renal damage.

PMID- 19590240
TI  - Heme oxygenase-1 inducer hemin attenuates the progression of remnant kidney
      model.
AB  - BACKGROUNDS/AIMS: Heme oxygenase-1 (HO-1) has been shown to protect against
      fibrotic proliferation and apoptosis in several models of renal damage. The
      purpose of this study was to evaluate the impact of a treatment with the HO-1
      inducer hemin on the progression of chronic kidney disease in nephrectomized rats
      versus the AT1 receptor antagonist losartan. METHODS: The rats underwent 5/6
      renal ablation and after the procedure received either losartan (20 mg/kg/day; n
      = 9), hemin (50 mg/kg/twice a week; n = 8) or vehicle (n = 8) over a 12-week
      period. At week 12, blood pressure was measured, urine, blood and remnant kidney
      were collected for biochemical (proteinuria, urea, creatinine) and
      histopathological (degrees of glomerulosclerosis and tubular atrophy) analysis.
      The expressions of HO-1, bone morphogenic protein 7 (BMP-7) and TGF-beta were
      assessed by immunochemistry, and the level of the apoptosis marker protein
      caspase-3 by Western blot, on the remnant kidney. RESULTS: Hemin significantly
      reduced blood pressure, proteinuria, inhibited the expression of TGF-beta and
      caspase-3 protein and increased BMP-7 expression protein. Hemin-treated rats had
      lower glomerulosclerosis and tubular atrophy indexes than controls. CONCLUSION:
      Hemin treatment attenuates the progression of chronic kidney disease and appears
      more efficient than losartan in our rat model hypothetically because of the
      impact of hemin on the renal expression of BMP-7.

PMID- 19590241
TI  - Expression of the chemokine fractalkine (FKN/CX3CL1) by podocytes in normal and
      proteinuric rat kidney glomerulus.
AB  - BACKGROUND/AIMS: A chemokine fractalkine (FKN/CX3CL1) is induced primarily by
      endothelial cells and accumulates inflammatory cells via its receptor CX3CR1.
      Since glomerular preferential expression of FKN/CX3CL1 gene was reported in
      normal human kidney, we presumed FKN/CX3CL1 might play some roles in glomerular
      physiology. The purpose of this study is to examine the expression and
      localization of FKN/CX3CL1 in normal and proteinuric glomeruli. METHODS: Normal
      and proteinuric rat kidneys were studied. The gene and protein expressions of
      FKN/CX3CL1 and CX3CR1 were examined by real-time RT-PCR, in situ hybridization
      and immunohistochemistry, Western blotting. RESULTS: By real-time RT-PCR,
      glomerular preferential expression of FKN/CX3CL1 was confirmed, whereas CX3CR1
      was detected in glomeruli and cortices. The localization of FKN/CX3CL1 gene and
      protein were demonstrated in glomerular cells including podocytes. In nephrotic
      puromycin aminonucleoside (PAN) nephrosis glomeruli, increased expression of
      FKN/CX3CL1 in podocyte was shown by immunohistochemistry. Western blotting showed
      that in nephrotic glomeruli, the membrane-anchored form of FKN/CX3CL1 was
      increased while the soluble form was decreased. CONCLUSION: The expression of
      FKN/CX3CL1 in normal podocytes and the increased expression of the membrane
      anchored form in nephrotic glomeruli strongly suggest that FKN/CX3CL1 may play
      roles in glomerular physiology such as maintaining glomerular filtration barrier.

PMID- 19590242
TI  - Effect of dsRNA on mesangial cell synthesis of plasminogen activator inhibitor
      type 1 and tissue plasminogen activator.
AB  - BACKGROUND/AIMS: Viral infections are a major problem worldwide and many of them
      are complicated by virally induced glomerulonephritides. Progression of kidney
      disease to renal failure is mainly attributed to the development of renal
      fibrosis characterized by the accumulation of extracellular matrix components in
      the mesangial cell compartment and the glomerular basement membrane. Plasminogen
      activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) are
      major regulators of plasmin generation and play an important role in generation
      and degradation of glomerular extracellular matrix components. Viral receptors
      expressed by mesangial cells (MC) are known to be key mediators in immune
      mediated glomerulonephritis. We investigated the effect of stimulation of the
      viral receptors toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I
      (RIG-I) on the expression of PAI-1 and t-PA. METHODS: Expression of PAI-1 and t
      PA in immortalized human MC stimulated with polyriboinosinic:polyribocytidylic
      acid [poly(I:C)] RNA and cytokines were analyzed by real-time RT-PCR and ELISA.
      RESULTS: Incubation of MC with poly(I:C) RNA to activate the viral receptors TLR3
      and RIG-I upregulates the expression of PAI-1 and t-PA. Knockdown of viral
      receptors with specific siRNA abolishes the induction of PAI-1 and t-PA.
      CONCLUSION: For the first time a link between the activation of viral receptors
      on MC and potentially causative agents in the development of glomerulosclerosis
      and tubulointerstitial fibrosis is shown. The progression of inflammatory
      processes to glomerulosclerosis can be postulated to be directly enhanced by
      viral infection.

PMID- 19590243
TI  - Soluble fas antigen and soluble fas ligand in intrauterine growth restriction.
AB  - BACKGROUND: The Fas-Fas ligand (FasL) pathway of apoptosis contributes to immune
      tolerance at the fetomaternal interface and has been ascribed a role in
      implantation and placental development. Intrauterine growth restriction (IUGR)
      may be associated with impaired maternal-fetal tolerance, resulting in increased
      trophoblast apoptosis and uteroplacental vascular insufficiency. OBJECTIVES: To
      investigate soluble Fas (sFas) and FasL (sFasL) concentrations in maternal, fetal
      and neonatal serum of IUGR and appropriate-for-gestational-age (AGA) pregnancies.
      METHODS: Circulating sFas and sFasL concentrations were determined in 40 mothers
      and their 20 IUGR (due to several etiologies) and 20 AGA singleton full-term
      fetuses and neonates on postnatal day 1 (N1) and 4 (N4). RESULTS: No significant
      differences in sFas and sFasL concentrations were observed between groups. In
      both groups, maternal sFas concentrations were increased compared to fetal, N1
      and N4 ones (p< or =0.005 in AGA and p < 0.001 in IUGR, in all cases). On the
      other hand, maternal sFasL concentrations were lower compared to fetal, N1 and N4
      ones (p < 0.001 in all cases). Fetal sFasL concentrations were increased compared
      to maternal, but lower compared to N4 sFasL ones (p < 0.001 in AGA and p < or =
      0.020 in IUGR, in all cases). N4 sFasL concentrations were elevated compared to
      N1 ones (p < 0.001). CONCLUSIONS: Circulating maternal, as well as fetal sFas and
      sFasL concentrations do not differ between AGA controls and IUGR cases,
      irrespectively of the etiology of the latter. Furthermore, the results of this
      study imply an acceleration of Fas-FasL-mediated apoptosis during delivery and a
      respective decrease postpartum in both normal and IUGR pregnancies.

PMID- 19590244
TI  - Effects of lutein on oxidative stress in the term newborn: a pilot study.
AB  - BACKGROUND: Oxidative stress (OS) plays a crucial role in pathological conditions
      during the early neonatal period. The newborns are susceptible to oxidative
      damage due to high metabolic rate and low levels of antioxidant enzymes. Lutein
      has been found to have protective functions in adult humans as antioxidant. AIM:
      To evaluate the effects of lutein on OS in newborns. We tested the hypothesis
      that lutein would act both by increasing antioxidant capacity and inhibiting OS.
      METHODS: This was a randomized, double-blind, placebo-controlled, single-center
      study. 20 healthy term newborns were assigned to receive lutein or placebo
      (lutein and control group, respectively) at 12 and 36 h after birth. Total
      hydroperoxides (TH), as marker of OS, and biological antioxidant potential (BAP),
      as marker of antioxidant power, were detected on cord blood and at 48 h of life
      in all babies. RESULTS: TH significantly increased from birth to 48 h in the
      control group (p = 0.02), but not in the lutein group. In the lutein group, BAP
      significantly increased after 48 h (p = 0.02), showing a strengthening of
      antioxidant activity due to lutein. At 48 h of life, compared with those in the
      control group, neonates assigned to receive lutein had significantly lower TH
      levels (p = 0.04) and higher BAP levels (p = 0.028). CONCLUSIONS: Lutein
      administration in newborns increases the levels of BAP decreasing TH. The
      enhancement of antioxidant activity in plasma clearly results in protecting
      newborn from perinatal OS. These preliminary results, adding a new contribution
      in antioxidant strategies, strongly require to be confirmed by RCT.

PMID- 19590245
TI  - Evaluation of urinary S100B protein level and lactate/creatinine ratio for early
      diagnosis and prognostic prediction of neonatal hypoxic-ischemic encephalopathy.
AB  - BACKGROUND: Early identification and prevention of hypoxic-ischemic
      encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological
      dysfunction. OBJECTIVE: To analyze the diagnostic and prognostic values of
      urinary S100B level and lactate/creatinine ratio in newborns with HIE. METHODS:
      Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled.
      The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental
      Screening Test were scored. The concentration of urinary S100B protein was
      determined using the S100B enzyme-linked immunosorbent assay and the levels of
      urinary lactate and creatinine were measured with the enzyme colorimetric method.
      RESULTS: Urinary S100B level on days 1-3 after birth and lactate/creatinine ratio
      on day 1 were significantly higher in newborns with HIE than those in the control
      group. Both indexes were positively correlated with the clinical grading of HIE.
      A cutoff value for the S100B level of 0.47 microg/l on day 3 after birth had a
      sensitivity of 90% and specificity of 92% for prediction of HIE. A
      lactate/creatinine ratio of more than 0.55 on day 1 showed the highest
      sensitivity (92%) and specificity (90%). A combination of both indexes improved
      the sensitivity and specificity to 99 and 97%, respectively. A negative
      correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1-3
      after birth with the NBNA score was identified on days 3, 7 and 14 after birth.
      The Developmental Screening Test score of 36 newborns with HIE within 6 months
      after birth showed that 65% of infants with moderate and high HIE had an abnormal
      developmental quotient. CONCLUSION: These data suggest that early measurement of
      both S100B level and lactate/creatinine ratio in the urine of newborns with HIE
      is a practical convenient and sensitive way to improve diagnosis on the third day
      of life and prognostic prediction of HIE.

PMID- 19590246
TI  - Behavioural effects of near-term acute fetal hypoxia in a small precocial animal,
      the spiny mouse (Acomys cahirinus).
AB  - We have previously developed a model of near-term intra-uterine hypoxia producing
      significant neonatal mortality (37%) in a small laboratory animal - the spiny
      mouse - which has precocial offspring at birth. The aim of the present study was
      to determine if this insult resulted in the appearance of behavioural
      abnormalities in those offspring which survived the hypoxic delivery. Behavioural
      tests assessed gait (using footprint patterns), motor coordination and balance on
      an accelerating rotarod, and spontaneous locomotion and exploration in an open
      field. We found that the near-term acute hypoxic episode produced a mild
      neurological deficit in the early postnatal period. In comparison to vaginally
      delivered controls, hypoxia pups were able to remain on the accelerating rotarod
      for significantly shorter durations on postnatal days 1-2, and in the open field
      they travelled significantly shorter distances, jumped less, and spent a greater
      percentage of time stationary on postnatal days 5 and 15. No changes were
      observed in gait. Unlike some rodent models of cerebral hypoxia-ischaemia,
      macroscopic examination of the brain on postnatal day 5 showed no gross cystic
      lesions, oedema or infarct. Future studies should be directed at identifying
      hypoxia-induced alterations in the function of specific brain regions, and
      assessing if maternal administration of neuroprotective agents can prevent
      against hypoxia-induced neurological deficits and brain damage that occur at
      birth.

PMID- 19590247
TI  - The Neonatal European Study of Inhaled Steroids (NEUROSIS): an eu-funded
      international randomised controlled trial in preterm infants.

PMID- 19590248
TI  - An inner medullary concentrating process actuated by renal pelvic/calyceal muscle
      contractions: assessment and hypothesis.
AB  - We propose a mechanism of an inner medullary concentrating process in which water
      extraction is accomplished by a colloid osmotic mechanism and hydrostatic
      pressure. There are 3 essential features of the proposal: 1. the fluid
      compartmental structure of the inner medullary interstitium: owing to molecular
      exclusion, negatively charged macromolecules, i.e. hyaluronan and extravasated
      plasma albumin form separate compartments (the HA and the EPA compartments); the
      resulting Gibbs-Donnan effect governs the movements of both ions and water. 2.
      NaCl, in high concentration in the inner medulla conditioned by the outer
      medullary countercurrent processes, significantly reduces the equilibrium colloid
      osmotic pressure between these compartments. 3. Urea, also accumulated here by
      special transport mechanisms, increases the mobility of water molecules and the
      flexibility of the HA fibrils by loosening hydrogen bonds. These features suggest
      that rhythmic, small pressure increases of the pelvic/calyceal muscles squeeze
      dilute fluid out of the HA compartment and, at the same time, accelerate the
      outflow of fluid and albumin into the ascending vasa recta from the EPA
      compartment. Further, they suggest a mechanism for the phenomenon that living
      organisms utilize hydrostatic pressure generated by muscle contractions in water
      economy namely, concentrating and diluting body fluids.

PMID- 19590249
TI  - Decorin suppresses bone metastasis in a breast cancer cell line.
AB  - Decorin, the prototype of an expanding family of small leucine-rich
      proteoglycans, is involved in a number of cellular processes including matrix
      assembly, fibrillogenesis and the control of cell proliferation. In this study,
      we investigated the role of decorin in suppressing tumor aggressiveness and bone
      metastases. We used a metastatic breast cancer cell line, MDA-MB-231, to show
      that decorin causes marked growth suppression bothin vitro and in vivo. A
      cytomegaloviral vector containing the decorin transgene caused greatly reduced
      cell growth, motility and observed metastases. Bone metastases were decreased by
      >90% upon decorin transfection. These results demonstrate a novel role for
      decorin in the reduction or prevention of tumor metastases in this breast cancer
      model and could eventually lead to improved therapies for metastatic breast
      cancer.

PMID- 19590250
TI  - Computer-based test to quantify the Pulfrich stereophenomenon.
AB  - BACKGROUND: Many eye and brain diseases may induce a spontaneous Pulfrich
      phenomenon (PP), a stereoillusion leading to misjudgments of objects moving in a
      frontoparallel plane. Since, until now, no simple PP quantification method has
      been available, a computer pendulum (CP) system was developed and evaluated.
      METHODS: In 5 normal subjects, PP was induced with different neutral density
      filters. The resulting retardations were measured with the gold standard (a
      mechanical pendulum; MP), and compared to a CP, allowing the generation of
      interocular image phase shifts. RESULTS: A high correlation between MP and CP was
      found (r = 0.97, p < 0.001; slope 0.91, p > 0.1 for difference with slope 1.0). A
      multiple linear regression showed a significant influence of the filter density
      and the subject tested. The type of pendulum (MP or CP) and the side on which the
      filter was held were nonsignificant. CONCLUSIONS: A CP allowing an interocular
      image phase shift can be used as an alternative to a MP for quantification of a
      PP. Thus, this principle would allow the development of software or an Internet
      based test for PP quantification. However, in some subjects, the CP will
      overestimate and in others underestimate the real retardation measured with the
      MP.

PMID- 19590251
TI  - Photopic negative response reflects severity of ocular circulatory damage after
      central retinal artery occlusion.
AB  - PURPOSE: To determine the relationship of the photopic negative response (PhNR)
      of the photopic electroretinogram (ERG) with the degree of circulatory
      disturbances in eyes following central retinal artery occlusion (CRAO). METHODS:
      The circulatory disturbance was graded as mild (group 1) when the arm-to-retina
      transmission time was <30 s, moderate (group 2) when the time was >30 s and
      severe (group 3) when concurrent choroidal circulatory damage was found. For
      statistical analysis, groups 1, 2 and 3 were scored as 1, 2 and 3, respectively.
      Photopic ERGs were elicited by either short-flash (SF) or long-flash (LF)
      stimuli. RESULTS: Both the SF and LF PhNR were significantly reduced in groups 2
      and 3. The PhNR amplitude was negatively correlated with the severity of the
      ocular circulatory disturbances (p = 0.0498, rho = -0.507 for SF PhNR; p =
      0.0050, rho = -0.750 for LF PhNR). CONCLUSION: The amplitude of the PhNR became
      more reduced as the severity of the circulatory disturbances increased in eyes
      with CRAO.

PMID- 19590252
TI  - Comparative study of intravitreal bevacizumab (Avastin) versus ranibizumab
      (Lucentis) in the treatment of neovascular age-related macular degeneration.
AB  - AIMS: To compare the safety and efficacy of 2 anti-vascular-endothelial-growth
      factor agents - bevacizumab (Avastin) versus ranibizumab (Lucentis) - in the
      treatment of patients with neovascular age-related macular degeneration (AMD).
      METHODS: Retrospective analysis of patients who received intravitreal injections
      of bevacizumab or ranibizumab for neovascular AMD. Primary outcome measures were
      best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessed
      by Spectral Domain scanning laser ophthalmoscope-optical coherence tomography (SD
      OCT). A secondary outcome measure was the report of any adverse events in the 2
      groups. RESULTS: The number of injections in the bevacizumab group was 184
      (average of 4.7 per eye) compared to 187 in the ranibizumab group (average of 5.5
      per eye). The mean logMAR equivalent of BCVA at 1 month after the injection
      improved by 0.18 in the bevacizumab group (p = 0.009) and by 0.13 in the
      ranibizumab group (p = 0.004). The average SD-OCT CFT decreased from 325 + or -
      72 to 300 + or - 69 microm in the bevacizumab group (p = 0.016) and from 307 + or
      - 57 to 289 + or - 56 microm in the ranibizumab group (p = 0.017). In the
      bevacizumab group, there was 1 event of lower extremity pain (0.54%) and 1 event
      of increased arterial blood pressure (0.54%). In the ranibizumab group, there
      were 2 events of transiently increased intraocular pressure (1.1%) and 1 event
      (0.53%) of intraocular inflammation following injection. CONCLUSIONS: Bevacizumab
      and ranibizumab treatments resulted in similar gains in visual acuity and
      reduction in macular thickness, documented each month following injection.
      Intravitreal bevacizumab appears to be as safe and effective as intravitreal
      ranibizumab in the treatment of exudative AMD.

PMID- 19590253
TI  - Extraction of a chronically implanted, microfabricated, subretinal electrode
      array.
AB  - PURPOSE: To assess the feasibility of extraction of a chronically implanted
      subretinal electrode array. METHODS: Inactive, polyimide strips (10 mm x 1.5 mm x
      15 microm) were surgically implanted into the subretinal space of 8 rabbits using
      a mostly ab externo approach. Pre- and postoperative clinical examinations,
      electroretinography and in some cases optical coherence tomography were performed
      to follow the course of the eyes. Two months after implantation, the polyimide
      strips were extracted from 5 eyes; 2 animals kept the implants and served as
      controls. All animals were then sacrificed and eyes enucleated for histological
      examination. RESULTS: All 8 surgeries yielded successful placement of the arrays
      into the subretinal space. All 5 extraction surgeries were performed without
      obvious complications. Clinical examinations and electroretinography did not
      reveal any significant abnormalities. The histological examinations showed
      alterations from normal anatomy in all animals; the anatomical changes in the
      explanted animals were relatively mild and confined to the area of the surgery.
      CONCLUSIONS: Successful extraction of electrode arrays from the subretinal space
      of rabbits can be reliably performed 2 months after implantation, which is beyond
      the time period when postoperative scarring would be most intense.

PMID- 19590254
TI  - Primers on molecular pathways - ion channels: key regulators of pancreatic
      physiology.
AB  - Ion transport across the cellular plasma membrane is important in almost every
      physiological process. This phenomenon is driven by the coordinated action of
      carriers, pumps and channels, which move ions in and out the cells and between
      different organelles. Ion channels are transmembrane proteins that provide a
      continuous aqueous pore through which ions can selectively move. The interest in
      these molecules has increased due to the recognition of diverse pathologies
      related with mutations in genes encoding these transmembrane proteins, now known
      as channelopathies. Ion channels play a variety of functions in the pancreas.
      Here, we briefly describe ion transport characteristics as well as their role in
      pancreas physiology and pathophysiology.

PMID- 19590256
TI  - Comparative effects of chlormadinone acetate and its 3alpha- and 3beta-hydroxy
      metabolites on progesterone, androgen and glucocorticoid receptors.
AB  - AIM/METHODS: In vitro binding tests to human receptors and in vivo functional
      activities in animals were used to compare the effects of the progestin
      chlormadinone acetate (CMA) and its 3alpha- and 3beta-hydroxy metabolites (3alpha
      OH-CMA and 3beta-OH-CMA) on progesterone, androgen and glucocorticoid receptors.
      RESULTS: CMA, 3alpha-OH-CMA, 3beta-OH-CMA and the reference progestin R5020 bound
      to human progesterone receptor with Ki values of 2.5 nm, 13 nm, 6.0 nm and 4.3
      nm, respectively. Binding affinities to the human androgen receptor were
      characterized by Ki values of 3.8 nM for CMA, 83 nM for 3alpha-OH-CMA, 20 nM for
      3beta-OH-CMA and 2.9 nM for the reference androgen methyltrienolone. The Ki
      values for binding to the human glucocorticoid receptor were 16 nM for CMA, 69 nM
      for 3alpha-OH-CMA, 21 nM for 3beta-OH-CMA and 1.2 nM for the glucocorticoid
      dexamethasone. In the rabbit endometrial proliferation test CMA, 3alpha-OH-CMA
      and 3beta-OH-CMA (5 and 45 microg/kg p.o. for 5 days) had similar progestomimetic
      activities. CMA, 3alpha-OH-CMA and, to a lesser extent, 3beta-OH-CMA (4.64 and
      21.5 mg/kg p.o. for 7 days) inhibited testosterone-stimulated growth of prostate
      and seminal vesicles in castrated rats showing antiandrogenic activities.
      Glucocorticoid properties were demonstrated for CMA and 3alpha-OH-CMA (21.5 and
      100 mg/kg p.o. for 6 days) but not for 3beta-OH-CMA as reduction in thymus and
      adrenal gland weights in immature rats. CONCLUSION: Binding assays at human
      receptors showed similarly high affinities of CMA with the progesterone and
      androgen receptors and a 5 times lower affinity with the glucocorticoid receptor.
      At all receptor types, CMA had the highest, 3alpha-OH-CMA the lowest and 3beta-OH
      CMA an intermediate affinity. Animal studies revealed progestomimetic and
      antiandrogenic activities of CMA, 3alpha-OH-CMA and 3beta-OH-CMA and
      glucocorticoid activities of CMA and 3alpha-OH-CMA.

PMID- 19590258
TI  - Torticollis under cyclobenzaprine.
AB  - The muscle-relaxing 5-HT(2) receptor antagonist cyclobenzaprine is structurally
      closely related to amitriptyline. It is widely used to treat patients presenting
      with back pain and fibromyalgia. Very rarely cyclobenzaprine toxicity can result
      in extrapyramidal symptoms, but occurrence of torticollis has not been reported
      so far. We report on a patient presenting with torticollis and myoclonic
      movements after treatment with cyclobenzaprine, who was successfully treated with
      intravenous biperiden. This case might be additional evidence for the necessity
      of appropriate dosage in case of liver impairment. Secondly there are possibly
      consequences as regards the therapy of motor side effects.

PMID- 19590257
TI  - Specificity of Gbetagamma signaling depends on Galpha subunit coupling with G
      protein-sensitive K(+) channels.
AB  - Many neurotransmitters activate G-protein-gated inwardly rectifying K(+) (Kir3)
      channels by stimulating G-protein-coupled receptors. However, in native systems,
      only receptors coupled to pertussis-toxin (PTX)-sensitive G proteins (Gi/Go) have
      been shown to be able to activate Kir3 channels through the betagamma subunits of
      G proteins (Gbetagamma), whereas activation of receptors coupled to PTX
      insensitive G proteins such as Gq or Gs do not activate Kir3 channels. The
      question remains as to how signaling specificity is achieved and what are its key
      determinants. In this study, we have used the Xenopus oocyte expression system to
      investigate specific activation of Kir3 channels by heterotrimeric G proteins. We
      have demonstrated the activation of Kir3.4 channels by agonist stimulation of non
      PTX-sensitive G proteins under conditions of Galpha subunit overexpression. We
      present evidence to suggest a key role for the coupling efficiency of Galpha
      subunits in determining the specificity of Gbetagamma signaling to the channel.

PMID- 19590259
TI  - Genetic aspects of the obstructive sleep apnoea/hypopnoea syndrome--is there a
      common link with obesity?
AB  - Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the third most common
      respiratory condition after asthma and chronic obstructive airway disease
      affecting approximately 2-4% of the middle-aged population. OSAHS has a
      hereditary component but owing to difficulties with phenotyping, its genetic
      basis has been difficult to elucidate. Despite this, limited progress has been
      made in considering the genetic basis of the 'intermediate phenotypes' of OSAHS
      such as craniofacial structure and upper airway control. Obesity is a risk factor
      for the development of OSAHS. The genetics of obesity are complex, but advances
      have been made recently using genome-wide association studies. Some authors
      postulate that OSAHS and common obesity share many pathophysiological pathways.
      However, the genes underpinning the development of sleep-disordered breathing and
      obesity are likely to be different, despite phenotypes that appear to overlap and
      influence each other's expression. This paper focuses on human studies over
      viewing the most recent work in the area and includes a brief discussion on
      methods of genetic studies.

PMID- 19590255
TI  - SD0006: a potent, selective and orally available inhibitor of p38 kinase.
AB  - SD0006 is a diarylpyrazole that was prepared as an inhibitor of p38 kinase-alpha
      (p38alpha). In vitro, SD0006 was selective for p38alpha kinase over 50 other
      kinases screened (including p38gamma and p38delta with modest selectivity over
      p38beta). Crystal structures with p38alpha show binding at the ATP site with
      additional residue interactions outside the ATP pocket unique to p38alpha that
      can confer advantages over other ATP competitive inhibitors. Direct correlation
      between inhibition of p38alpha activity and that of lipopolysaccharide-stimulated
      TNFalpha release was established in cellular models and in vivo, including a
      phase 1 clinical trial. Potency (IC(50)) for inhibiting tumor necrosis factor
      alpha (TNFalpha) release, in vitro and in vivo, was <200 nmol/l. In vivo, SD0006
      was effective in the rat streptococcal-cell-wall-induced arthritis model, with
      dramatic protective effects on paw joint integrity and bone density as shown by
      radiographic analysis. In the murine collagen-induced arthritis model,
      equivalence was demonstrated to anti-TNFalpha treatment. SD0006 also demonstrated
      good oral anti-inflammatory efficacy with excellent cross-species correlation
      between the rat, cynomolgus monkey, and human. SD0006 suppressed expression of
      multiple proinflammatory proteins at both the transcriptional and translational
      levels. These properties suggest SD0006 could provide broader therapeutic
      efficacy than cytokine-targeted monotherapeutics.

PMID- 19590261
TI  - Epidural anesthesia for placement of spinal cord stimulators with paddle-type
      electrodes.
AB  - BACKGROUND/AIMS: Placement of paddle electrodes for spinal cord stimulation is
      usually performed under local anesthesia as the patient must be alert and
      cooperative during the procedure. This is often difficult, and involves
      significant discomfort for the patient. We explore the placement of spinal cord
      stimulators (SCS) under epidural anesthesia. METHODS: Fifteen consecutive
      patients underwent single-shot epidural anesthesia prior to placement of the SCS.
      Patient perception of paresthesias during intraoperative stimulation was compared
      to preoperative pain dermatomes indicated by the patient. The ability to produce
      paresthesias as well as the voltage required to produce paresthesias under
      anesthesia were recorded. Patient demographics, amount and concentration of
      epidural drugs, use of local anesthetic or sedatives, and any complications were
      also recorded. RESULTS: Epidural anesthesia was successfully induced in 14
      patients. All patients were alert and cooperative. Paresthesias in appropriate
      dermatomes were induced in all patients. No local anesthetic or sedatives were
      used. The voltage required to induce paresthesias was double that required to
      maintain stimulation once the epidural had worn off. CONCLUSION: Epidural
      anesthesia provides a safe and effective means of placing SCS with paddle-type
      electrodes. There is no patient discomfort, and paresthesias are consistently
      elicited in appropriate areas in all patients.

PMID- 19590262
TI  - Bibliography-Editors' selection of current world literature.

PMID- 19590260
TI  - Historic evolution of open cingulectomy and stereotactic cingulotomy in the
      management of medically intractable psychiatric disorders, pain and drug
      addiction.
AB  - Stereotactic cingulotomy constitutes a psychosurgical procedure nowadays
      advocated in the treatment of medically intractable obsessive-compulsive
      disorder, chronic pain and drug addiction. From its theoretical conception to the
      first cingulectomies performed and modern stereotactic-guided cingulotomies,
      various target localization methods, different surgical techniques, and numerous
      lesioning devices have been utilized. In the current article, the authors
      performed a literature review related to cingular lesion placement in an effort
      to identify misconceptions of the past, recapitulate existing knowledge and
      recognize targets for further research. The initial animal and human
      electrophysiologic experimental data regarding the role of the cingulate cortex
      in various behavioral and cognitive functions were meticulously reviewed. The
      clinical indications, surgical technique and the clinical results and
      complications of open cingulectomies were examined. The anatomic target
      localization methodologies, surgical technique, and the outcome of the initial
      stereotactic cingulotomy procedures were reviewed, and the evolution of the
      imaging techniques, stereotactic devices, and lesioning strategies were followed.
      The modern advanced surgical techniques, clinical outcome and the procedure
      associated complications were analyzed with particular emphasis on the emotional,
      behavioral, and cognitive procedure-induced changes. Large-scale prospective
      studies with strict inclusion and well-defined, objective outcome criteria are
      necessary for defining the role of stereotactic cingulotomy in the current
      psychosurgical armamentarium.

PMID- 19590264
TI  - RSO interview with Myung Jo. Interview by Rene Michel.

PMID- 19590265
TI  - Developing in-vitro bioassay goals for plutonium and uranium for Department of
      Energy facilities.
AB  - On 8 June 2007, the Department of Energy amended its occupational radiation
      protection rule Title 10 Code of Federal Regulations Part 835, Occupational
      Radiation Protection. Department of Energy revised the radiation weighting
      factors, tissue weighting factors and most of the dosimetric terms used in Title
      10 Code of Federal Regulations Part 835 to reflect the recommendations for
      assessing dose and associated terminology from ICRP Publication 60, 1990
      Recommendations of the ICRP on Radiological Protection. In support of the
      amendment, Department of Energy is revising its guidance documents on
      establishing bioassay result goals, which are used in assessing bioassay
      capabilities and establishing bioassay frequencies. The revised guidance is based
      on the updated dosimetric models and provides a useful tool for evaluating
      aspects of a bioassay program which may need revision.

PMID- 19590266
TI  - Potential for contamination during removal of radioactive seeds from surgically
      excised tissue.
AB  - The purpose of this study was to determine whether the use of a scalpel or
      electrocautery to remove radioactive sealed sources ("seeds") from surgically
      excised tissue could damage the seed and cause it to leak its radioactive
      contents. Attempts were made to cut or burn Oncura Model 6711 non-radioactive
      seeds while in pig muscle or on a stainless steel plate. Additionally, one active
      125I seed was purposely charred using pressure with an electrocautery knife to
      see whether the casing could be damaged. Electron microscopy scanning was
      performed on the dummy seeds to determine if the integrity of the metal casing
      had been compromised. Two types of leak tests were performed on the active seed
      to verify the presence or absence of loose contamination. The seed casing was not
      damaged from either use of a scalpel or electrocautery when the seed was in
      tissue. The active seed was not found to be leaking after applying pressure with
      an electrocautery knife while the seed was on a stainless steel plate. We
      conclude that removal of active Model 6711 seeds from surgically excised tissue
      can be done safely with a scalpel or electrocautery because constant, firm
      pressure cannot be applied to the seed. This is likely true for seeds made of
      similar materials.

PMID- 19590267
TI  - The possible effect on personnel dose by two copper filters covering Element 1 of
      the Harshaw 8814 TLD badge.
AB  - Ongoing uncertainties have existed regarding possible effects at low photon
      energies of two copper filters covering Element 1 of the Harshaw Type-8814
      thermoluminescent dosimeter badge casing. To address these, Brookhaven National
      Laboratory's (BNL) Personnel Monitoring Group conducted a test in which Type-8814
      badges with one copper filter covering Element 1 were irradiated at several low
      energy levels side-by-side with the same number of badges with two copper filters
      covering Element 1. A review of exposures to personnel at Brookhaven Laboratory
      to possible low-energy photon flux was also conducted. From both the test and the
      review of exposures, it can be concluded that, for radiological work under the
      conditions at BNL, there is no apparent dosimetric difference if one or two
      copper filters cover Element 1 of the Type-8814 badge.

PMID- 19590268
TI  - Disposal of a 60Co self-shielded irradiator through the Department of Energy's
      Off-Site Source Recovery Project.
AB  - An Atomic Energy of Canada Limited Gamma Cell 220 self-shielded irradiator
      acquired in 1974 by the VA Eastern Colorado Health Care System was disposed of
      through the Department of Energy's Off-Site Source Recovery Project in 2006.

PMID- 19590269
TI  - Policy decision-making under scientific uncertainty: radiological risk assessment
      and the role of expert advisory groups.
AB  - Standard-setting agencies such as the U.S. Nuclear Regulatory Commission and the
      U.S. Environmental Protection Agency depend on advice from external expert
      advisory groups on matters of public policy and standard-setting. Authoritative
      bodies including the National Research Council and the National Council on
      Radiation Protection and Measurements provide analyses and recommendations that
      enable the technical and scientific soundness in decision-making. In radiological
      protection the nature of the scientific evidence is such that risk assessment at
      radiation doses typically encountered in environmental and occupational settings
      is highly uncertain, and several policy alternatives are scientifically
      defensible. The link between science and policy is problematic. The fundamental
      issue is the failure to properly consider risk assessment, risk communication,
      and risk management and then consolidate them in a process that leads to sound
      policy. Authoritative bodies should serve as unbiased brokers of policy choices
      by providing balanced and objective scientific analyses. As long as the policy
      decision environment is characterized by high scientific uncertainty and a lack
      of values consensus, advisory groups should present unbiased evaluations of all
      scientifically plausible alternatives and recommend selection criteria that
      decision makers can use in the policy-setting process. To do otherwise (e.g., by
      serving as single position advocates) weakens decision-making by eliminating
      options and narrowing discussions of scientific perspectives. Understanding
      uncertainties and the limitations on available scientific information and
      conveying such information to policy makers remain key challenges for the
      technical and policy communities.

PMID- 19590270
TI  - Estimation of individualized radiation risk from chronic occupational exposure in
      Russia.
AB  - Internationally, the upper limit of acceptable individualized risk from
      occupational exposure for nuclear industry workers is determined by the death
      probability 10(-3) y(-1). The same risk value of 10(-3) y(-1) is established by
      the radiation safety standards currently in force in Russia. The United Nations
      Scientific Committee on the Effects of Atomic Radiation has proposed the formulas
      for estimating individualized risk of developing cancer with allowance for
      radiation dose, age at exposure, attained age, and sex. This methodology is first
      applied to estimate individualized radiation risk for Russian nuclear industry
      workers (49,900 persons) who were monitored for radiation exposure through the
      use of personal dosimeters. The estimates show that in 2006 the threshold of 10(
      3) y(-1) for individualized risk is exceeded for 755 persons, which is 1.6% of
      all workers covered by personal dose monitoring. The excess absolute risk (EAR)
      and attributable risk (AR) were estimated for all cancers, solid cancers, and
      leukemias.

PMID- 19590272
TI  - Application of the Monte Carlo method to study the alpha particle energy spectra
      for radioactive aerosol sampled by an air filter.
AB  - An alpha spectrometer including a semi-conductor detector is commonly used for
      measurements of the emergent alpha particles from an air filter, on which was
      sampled a radioactive aerosol. The alpha spectrometry and the detection
      efficiency are necessary input information for real radioactivity measurements.
      The MCNPX code based on the Monte Carlo method has been applied to simulate the
      detection process in order to obtain spectrum peaks and determine the detection
      efficiency for modeled geometry. First simulations with MCNPX have been carried
      out in order to validate the alpha particle energy spectrometry of an
      electrodeposited solid source and an initial simulated filter model. Furthermore,
      to improve our first filter model, the real spatial distribution of radioactive
      aerosols across the filter thickness, found experimentally, is taken into account
      in a multi-layer filter model. Such an alpha particle distribution allows
      achieving an adequate simulation of the filter. Comparison between measured and
      simulated alpha spectra highlights the good agreement in spectral parameters and
      in detection efficiency even under different aerosol spatial distributions inside
      the volume of the filter.

PMID- 19590271
TI  - Investigation of chitosan for decorporation of 60Co in the rat.
AB  - With the increased threat of terrorist release of radioactive materials, there is
      a need for non-toxic decorporation agents to treat internal contamination with
      radionuclides. In this study, low molecular weight chitosan was evaluated for
      decorporation of radioactive cobalt (60Co). The affinity of chitosan for Co(II)
      was tested in vitro using spectrophotometric and potentiometric titration
      techniques. For in vivo studies, the effect of chitosan on ingested 60Co was
      evaluated using F344 rats administered a single dose followed by oral chitosan.
      Chitosan was also evaluated for systemic decorporation of 60Co following
      intravenous injection with repeated chitosan administration over 5 d. Control
      animals received 60Co without chelation treatment. Excreta and tissues were
      collected for analysis using gamma-counting techniques. Results from in vitro
      experiments confirmed the binding of Co(II) to chitosan, with the postulated
      formation of a mixed cobalt-chitosan-hydroxide complex species; a stability
      constant was calculated for this complex. For in vivo studies, oral
      administration of chitosan significantly reduced systemic absorption of orally
      administered 60Co as evidenced by an increase in fecal elimination and decrease
      in urinary elimination. However, oral administration of chitosan lactate slightly
      decreased fecal excretion of 60Co. Further, oral administration of chitosan
      significantly reduced 60Co levels in kidney, liver, and skeleton compared to
      control animals receiving 60Co alone. By the i.v. route, chitosan slightly
      reduced levels of 60Co in tissues compared to controls, although statistically
      significant reductions were only observed for blood and kidney. Overall, this
      commercially available chitosan oligosaccharide exhibited promising potential;
      further studies are warranted to evaluate the optimal dosing regimen and chemical
      modifications to increase effectiveness.

PMID- 19590274
TI  - Overview of hazard assessment and emergency planning software of use to RN first
      responders.
AB  - There are numerous software tools available for field deployment, reach-back,
      training and planning use in the event of a radiological or nuclear terrorist
      event. Specialized software tools used by CBRNe responders can increase
      information available and the speed and accuracy of the response, thereby
      ensuring that radiation doses to responders, receivers, and the general public
      are kept as low as reasonably achievable. Software designed to provide health
      care providers with assistance in selecting appropriate countermeasures or
      therapeutic interventions in a timely fashion can improve the potential for
      positive patient outcome. This paper reviews various software applications of
      relevance to radiological and nuclear events that are currently in use by first
      responders, emergency planners, medical receivers, and criminal investigators.

PMID- 19590273
TI  - Field investigation of surface-deposited radon progeny as a possible predictor of
      the airborne radon progeny dose rate.
AB  - The quantitative relationships between radon gas concentration, the surface
      deposited activities of various radon progeny, the airborne radon progeny dose
      rate, and various residential environmental factors were investigated through
      actual field measurements in 38 selected Iowa houses occupied by either smokers
      or nonsmokers. Airborne dose rate was calculated from unattached and attached
      potential alpha energy concentrations (PAECs) using two dosimetric models with
      different activity-size weighting factors. These models are labeled Pdose and
      Jdose, respectively. Surface-deposited 218Po and 214Po were found significantly
      correlated to radon, unattached PAEC, and both airborne dose rates (p < 0.0001)
      in nonsmoking environments. However, deposited 218Po was not significantly
      correlated to the above parameters in smoking environments. In multiple linear
      regression analysis, natural logarithm transformation was performed for airborne
      dose rate as the dependent variable, as well as for radon and deposited 218Po and
      214Po as predictors. An interaction effect was found between deposited 214Po and
      an obstacle in front of the Retrospective Reconstruction Detector (RRD) in
      predicting dose rate (p = 0.049 and 0.058 for Pdose and Jdose, respectively) for
      nonsmoking environments. After adjusting for radon and deposited radon progeny
      effects, the presence of either cooking, usage of a fireplace, or usage of a
      ceiling fan significantly, or marginally significantly, reduced the Pdose to 0.65
      (90% CI 0.42-0.996), 0.54 (90% CI 0.28-1.02), and 0.66 (90% CI 0.45-0.96),
      respectively. For Jdose, only the usage of a ceiling fan significantly reduced
      the dose rate to 0.57 (90% CI 0.39-0.85). In smoking environments, deposited
      218Po was a significant negative predictor for Pdose (RR 0.68, 90% CI 0.55-0.84)
      after adjusting for long-term 222Rn and environmental factors. A significant
      decrease of 0.72 (90% CI 0.64-0.83) in the mean Pdose was noted, after adjusting
      for the radon and radon progeny effects and other environmental factors, for
      every 10 additional cigarettes smoked in the room. A significant increase of 1.71
      in the mean Pdose was found for large room size relative to small room size (90%
      CI 1.08-2.79) after adjusting for the radon and radon progeny effects as well as
      other environmental factors. Fireplace usage was found to significantly increase
      the mean Pdose to 1.71 (90% CI 1.20-2.45) after adjusting for other factors.

PMID- 19590275
TI  - Relative radiological impact from a reactor accident in the case of emerging
      nuclear fuels.
AB  - An assessment has been carried out on the radiological impact on an area
      contaminated from an accident of a nuclear reactor loaded with different actinide
      fuels considered in transmutation and recycling schemes. The impact of these
      schemes is compared to reference cases of commercial UO2 and MOX fuels. The
      effective dose equivalent delivered to permanent residents has been calculated
      using the RESRAD code and used as an index for the assessment purposes. The
      highest and lowest doses would be delivered from the self-generating recycling of
      actinides in fast and thermal reactors, respectively. External irradiation is the
      main contributor to the dose delivered to the target population in comparison to
      ingestion and inhalation. The external dose delivered would be attributed for the
      first few years to 134Cs and for the following several tens of years to 137Cs.

PMID- 19590276
TI  - Radon exhalation rates from building materials using electret ion chamber radon
      monitors in accumulators.
AB  - An electret ion chamber (EIC) radon monitor in a sealed accumulator measures the
      integrated average radon concentration at the end of the accumulation duration.
      Theoretical equations have been derived to relate such radon concentrations (Bq
      m(-3) ) to the radon emanation rate (Bq d(-1)) from building materials enclosed
      in the accumulator. As an illustration, a 4-L sealable glass jar has been used as
      an accumulator to calculate the radon emanation rate from different granite
      samples. The radon emanation rate was converted into radon flux (Bq mm(-2) d(-1))
      by dividing the emanation rate by surface area of the sample. Fluxes measured on
      typical, commercially available granites ranged from 20-30 Bq m(-2) d(-1). These
      results are similar to the results reported in the literature. The lower limit of
      detection for a 2-d measurement works out to be 7 Bq m(-2) d(-1). Equations
      derived can also be used for other sealable accumulators and other integrating
      detectors, such as alpha track detectors.

PMID- 19590277
TI  - IAEA calls for enhanced radiation protection of patients.

PMID- 19590280
TI  - Caring for the pediatric patient in a remote location. Preface.

PMID- 19590281
TI  - Setting up for pediatric offsite anesthesiology.

PMID- 19590282
TI  - The child in MRI and CT: considerations and techniques.

PMID- 19590283
TI  - Pediatric malignancies and anesthesia in out-of-or locations.

PMID- 19590284
TI  - Pediatric procedures in interventional radiology.

PMID- 19590285
TI  - Radiation therapy in children.

PMID- 19590286
TI  - Anesthesia for pediatric airway endoscopy and upper gastrointestinal endoscopy.

PMID- 19590287
TI  - Cardiac catheterization laboratory: catheterization, interventional cardiology,
      and ablation techniques for children.

PMID- 19590288
TI  - Anesthetic management of epileptic pediatric patients.

PMID- 19590290
TI  - Impact of HIV status on outcome of infectious complications in intravenous drug
      users.

PMID- 19590291
TI  - Does episodic antiretroviral therapy increase HIV transmission risk compared with
      continuous therapy?

PMID- 19590297
TI  - Pelvic fracture of an adolescent ballerina.

PMID- 19590298
TI  - Extreme anemia in an injured Jehovah's Witness: a test of our understanding of
      the physiology of severe anemia and the threshold for blood transfusion.

PMID- 19590299
TI  - Angiographic embolization of an expanding breast hematoma after blunt trauma: a
      novel approach to a rare injury.

PMID- 19590300
TI  - Acute care congress on the future of emergency surgical care in the United
      States.
AB  - BACKGROUND: Multiple factors are contributing to overcrowded emergency
      departments and decreased patient access to emergency surgical care in the United
      States. METHODS: Under the leadership of the American Association for the Surgery
      of Trauma and the Centers for Disease Control, 15 national medical organizations
      came together in August 2008 for the Acute Care Congress on the Future of
      Emergency Surgical Care in the United States. The aim was to discuss the problems
      facing access to emergency surgical care and to propose an action plan for
      addressing them. RESULTS: Proposed solutions included ways to add to the
      dwindling surgical workforce, to more efficiently handle the rising public demand
      for emergency surgical services, to attempt to increase federal reimbursements
      and other payments for emergency surgical care, and to overcome limitations of
      existing laws on emergency care. CONCLUSIONS: Organizations affected by the
      problems with emergency surgical care should work together to set and augment the
      standard of emergency care in the United States. Joint efforts should include
      advocacy for legislative reform and additional governmental funding, development
      of national guidelines that will determine best practices for emergency surgical
      care, and increased research aimed at trauma prevention. Additionally, regional
      trauma systems should be integrated into a nationwide system that, ideally,
      encompasses nontrauma emergency surgical care.

PMID- 19590301
TI  - Treatment of chest wall implosion injuries without thoracotomy: technique and
      clinical outcomes.
AB  - BACKGROUND: Chest wall implosion injuries secondary to side impact are unusual
      but devastating injuries. The purpose of this series is to describe the clinical
      entity, present a surgical technique to reduce and repair the thoracic cage
      deformity without thoracotomy, and report outcomes in nine patients. STUDY:
      Institutional review board approved retrospective case series, surgical
      technique. SETTING: Level I Trauma Center. METHODS: Twenty-two patients were
      admitted during 7-year period with thoracic cage implosion injuries and multiple
      segmental rib fractures from a side impact mechanism. All patients' required
      mechanical ventilation and had an implosion deformity along the posterolateral
      thoracic cage, pulmonary contusion, and clavicular fractures. Nine patients
      underwent repair of rib fractures through a paramidline posterior approach
      without thoracotomy using standard 2.4-mm titanium plates. Seven patients with
      similar fracture pattern treated nonoperatively were used as a historical
      control. Total intubation time, intensive care unit (ICU) length of stay (LOS),
      and final shoulder function using the Constant Murley scoring system were
      compared between the two groups. RESULTS: Average age, male to female ratio, and
      injury severe score were comparable for both cohorts (p > 0.6). Average follow-up
      was 16 months versus 12 months for the operative and nonoperative groups,
      respectively, (p = 0.11). In the operative group, 8 of 9 (89%) patients were
      extubated within 24 hours of surgery; 3 of 9 (33%) were extubated in the
      operating room. In the operative group, seven patients underwent internal
      fixation of the clavicle and progressed to union with a mean Constant score of
      93. Nine patients had nonoperative treatment of the clavicle with a mean Constant
      score of 75 (p = 0.04). Total intubation time (1.9 days) was significantly
      shorter in the operative group than the nonoperative controls at 13.3 days (p <
      0.01) and length of ICU stay was also shortened at 5.7 (4-8) days versus 16.7 (10
      26) days, respectively, (p < 0.01). CONCLUSION: Chest wall implosion injuries
      with fixed deformities of the thoracic cage, multiple segmental rib fractures,
      and clavicular injury are a distinct clinical entity, which can be effectively
      managed with a posterior paramidline approach without thoracotomy. Reduction of
      the deformity and repair of the rib fractures led to a dramatic reduction in time
      to extubation, ICU LOS, and in-hospital complications including pneumonia and
      sepsis. Repair of the clavicular fracture appeared to be beneficial.

PMID- 19590303
TI  - The utility of computed tomography as a screening tool for the evaluation of
      pediatric blunt chest trauma.
AB  - BACKGROUND: There is a growing concern that computed tomography (CT) is being
      unnecessarily overused for the evaluation of pediatric patients. The purpose of
      this study was to analyze the trends and utility of chest CT use compared with
      chest X-ray (CXR) for the evaluation of children with blunt chest trauma.
      METHODS: A 4-year retrospective review was performed for pediatric patients who
      underwent chest CT within 24 hours of sustaining blunt trauma at a Level-I trauma
      center. Trends in the use of CT and CXR were documented, and results of radiology
      reports were analyzed and compared with clinical outcomes. RESULTS: Three hundred
      thirty-three children, mean age 11 years, had chest CTs, increasing from 5.5% in
      2001-2002 to 10.5% in 2004-2005 (p < 0.001). Conversely, in those children who
      underwent chest CT, the rate of initial CXR use decreased from 84% to 56% during
      the same period (p < 0.001). Twenty percent of chest CTs had significant positive
      findings. Six patients underwent emergency surgery for cardiac or arterial
      injuries, and all demonstrated abnormal findings on CXR or CT scout imaging. When
      compared with the CT, only 5% of initial CXRs falsely reported normal findings
      that may have altered management. CONCLUSIONS: CT use in children has increased
      rapidly for the initial evaluation of chest trauma, whereas CXR use has
      decreased. Despite this trend, CXR remains an acceptable screening tool to
      analyze which patients may require CT evaluation. A multidisciplinary approach is
      warranted to develop guidelines that standardize the use of CT and thereby
      decreases unnecessary radiation exposure to pediatric patients.

PMID- 19590302
TI  - Pulmonary contusion primes systemic innate immunity responses.
AB  - INTRODUCTION: Traumatic injury may result in an exaggerated response to
      subsequent immune stimuli such as nosocomial infection. This "second hit"
      phenomenon and molecular mechanism(s) of immune priming by traumatic lung injury,
      specifically, pulmonary contusion, remain unknown. We used an animal model of
      pulmonary contusion to determine whether the injury resulted in priming of the
      innate immune response and to test the hypothesis that resuscitation fluids could
      attenuate the primed response to a second hit. METHODS: Male, 8 to 9 weeks,
      C57/BL6 mice with a pulmonary contusion were challenged by a second hit of
      intratracheal administration of the Toll-like receptor 4 agonist,
      lipopolysaccharide (LPS, 50 microg) 24 hours after injury (injury + LPS). Other
      experimental groups were injury + vehicle or LPS alone. A separate group was
      injured and resuscitated by 4 cc/kg of hypertonic saline (HTS) or Lactated
      Ringer's (LR) resuscitation before LPS challenge. Mice were killed 4 hours after
      LPS challenge and blood, bronchoalveolar lavage, and tissue were isolated and
      analyzed. Data were analyzed using one-way analysis of variance with Bonferroni
      multiple comparison posttest for significant differences (*p < or = 0.05).
      RESULTS: Injury + LPS showed immune priming observed by lung injury histology and
      increased bronchoalveolar lavage neutrophilia, lung myeloperoxidase and serum IL
      6, CXCL1, and MIP-2 levels when compared with injury + vehicle or LPS alone.
      After injury, resuscitation with HTS, but not Lactated Ringer's was more
      effective in attenuating the primed response to a second hit. CONCLUSION:
      Pulmonary contusion primes innate immunity for an exaggerated response to a
      second hit with the Toll-like receptor 4 agonist, LPS. We observed synergistic
      increases in inflammatory mediator expression in the blood and a more severe lung
      injury in injured animals challenged with LPS. This priming effect was reduced
      when HTS was used to resuscitate the animal after lung contusion.

PMID- 19590304
TI  - Transfusion of aged packed red blood cells results in decreased tissue
      oxygenation in critically injured trauma patients.
AB  - BACKGROUND: Blood transfusion is a common event in the treatment of injured
      patients. The effect of red blood cell transfusion on tissue oxygenation is
      unclear. The transfusion of older blood has been shown to be detrimental in
      retrospective studies. This study aims to study the effect of the age of the
      blood transfused on the tissue oxygenation using near infrared spectroscopy.
      METHODS: Thirty-two critically injured trauma patients for whom a blood
      transfusion had been ordered were recruited. Each patient had a transcutaneous
      probe placed on the thenar eminence. The probe was placed 1 hour before the
      transfusion and left in place until 4 hours after transfusion. Tissue oxygen
      saturation (Sto2) was recorded every 2 minutes. The Sto2 area under the curve
      (AUC) over time periods was calculated. A control group (n = 16), not transfused,
      was recruited. The transfusion group was divided into two groups by blood age.
      One group received blood less than 21 days old, (new blood, n = 15) and the other
      received blood 21 days old or greater (old blood, n = 17). The data were analyzed
      for significance with Kendall's W and Wilcoxon's signed rank test (p < 0.05).
      RESULTS: Baseline characteristics such were not significantly different between
      groups. The baseline AUC did not differ between groups. The old blood group
      demonstrated a significant decline in Sto2 comparing its baseline period to its
      transfusion period (p < 0.05). There was no similar decline in the control group
      or the new blood group. The posttransfusion period AUC for the old blood group
      was also lower versus baseline (p = 0.06). There was a moderate correlation
      between increasing age of blood and decrease in oxygenation (r = 0.5).
      CONCLUSIONS: There was a decrease in peripheral tissue oxygenation in patients
      receiving older red blood cells. There was no oxygenation decrease in patients
      receiving blood less than 21 days. This indicates that factors in stored blood
      may influence the peripheral vasculature and oxygen delivery.

PMID- 19590305
TI  - Hemostatic resuscitation during surgery improves survival in patients with
      traumatic-induced coagulopathy.
AB  - BACKGROUND: Although hemostatic resuscitation with a 1:1 ratio of fresh-frozen
      plasma (FFP) to packed red blood cells (PRBC) after severe hemorrhage has been
      shown to improve survival, its benefit in patients with traumatic-induced
      coagulopathy (TIC) after >10 units of PRBC during operation has not been
      elucidated. We hypothesized that a survival benefit would occur when early
      hemostatic resuscitation was used intraoperatively after injury in patients with
      TIC. METHODS: A 7-year retrospective study of patients with emergency department
      diagnosis of TIC after transfusion of >10 units of PRBC in the operating room.
      TIC was defined as initial emergency department international normalized ratio >
      1.2, prothrombin time > 16 seconds, and partial thromboplastin time > 50 seconds.
      Patients were divided into FFP:PRBC ratios of 1:1, 1:2, 1:3, and 1:4. Patients
      with diagnosis of TIC who received transfusion of both FFP and PRBC during
      surgery were included. Other variables evaluated included age, gender, mechanism
      of injury, initial base deficit, mean operative time, trauma intensive care unit
      length of stay (TICU LOS) and Injury Severity Score. The primary outcome measure
      evaluated was the impact of the early FFP:PRBC ratio on mortality. RESULTS: Four
      hundred thirty-five patients underwent emergency operations postinjury and
      received FFP with >10 units of PRBC in the operating room; 135 (31.0%) of these
      patients had TIC and 53 died (39.5% mortality). Mean operative time was 137
      minutes (SD +/- 49). There were no differences with regard to age, gender,
      mechanism of injury, initial base deficit, or Injury Severity Score among all
      groups. A significant difference in mortality was found in patients who received
      >10 units of PRBC when FFP:PRBC ratio was 1:1 versus 1:4 (28.2% vs. 51.1%, p =
      0.03). Intermediate mortality rates were noted in patients with 1:2 and 1:3
      ratios (38% and 40%, respectively). From a linear regression model, 13 days of
      increased TICU LOS was observed among 1:4 group compared with 1:1 group (p <
      0.01). CONCLUSION: TIC is common after severe injury and is associated with a
      high mortality in patients transfused with >10 units of PRBC during surgery.
      Early hemostatic resuscitation during first hours after injury improves survival
      with shorter TICU LOS in patients with TIC.

PMID- 19590306
TI  - Comparison of the biomechanical behavior of the liver during frontal and lateral
      deceleration.
AB  - BACKGROUND: The trunk of a car occupant can be injured by a frontal or lateral
      impact. Lesions can be either intrusion injuries or due to the effects of
      deceleration alone. The aim of this study conducted with human cadavers was to
      explore the effects of deceleration on the liver during frontal or lateral
      deceleration. METHODS: Trunks previously instrumented with accelerometers in
      three sites, the left and right lobes of the liver and the retrohepatic inferior
      vena cava, were subjected to substantial deceleration in three orientations:
      frontal, left, and right lateral. The anatomic consequences and deceleration data
      were measured. A deceleration ratio was defined as a peak deceleration measured
      in the liver divided by peak deceleration imposed on the trunk. RESULTS: Peak
      deceleration imposed on the trunks was up to 60 g, which caused peak deceleration
      up to 26 g in the liver. No anatomic injury was observed. For each orientation,
      deceleration ratios were not significantly different among the three sites (p =
      0.64) or between left and right lateral decelerations (p = 0.12). Deceleration
      ratios were significantly different (p = 0.001) between frontal (3 sites
      combined) and lateral (3 sites of left and right lateral orientations combined)
      decelerations: 39.4% (+/-6) versus 48.4% (+/-11). CONCLUSIONS: In conclusion, at
      tested decelerations, under the hepatic injury threshold, cadaveric liver seemed
      to be subjected to higher deceleration when the trunk was decelerated in lateral
      than in frontal direction, without terminal impact.

PMID- 19590307
TI  - Single-dose etomidate for rapid sequence intubation may impact outcome after
      severe injury.
AB  - BACKGROUND: Etomidate is an induction agent used for the rapid sequence
      intubation (RSI) of trauma patients because of its favorable hemodynamic profile
      and rapid onset. However, recent studies have shown etomidate to decrease
      circulating cortisol concentrations, potentially influencing inflammation. We
      hypothesized that etomidate may alter the occurrence of acute respiratory
      distress syndrome (ARDS) in injury victims. METHODS: We analyzed data collected
      prospectively from a clinical trial of prehospital hypertonic saline
      administration. Post hoc, patients were grouped according to whether they did or
      did not receive etomidate for prehospital airway management. The incidence of
      ARDS was compared between the two groups by Fisher's exact test. Logistic
      regression was used to adjust for the effects of other known risk factors for
      ARDS. RESULTS: Over a 2-year period, 94 study patients underwent RSI, of which 35
      received etomidate (37%). There were no significant differences in demographic,
      physiology, anatomic injury scores, or use of hypertonic saline resuscitation
      between the groups. After adjusting for physiology, injury severity, and
      transfusion, etomidate use remained associated with ARDS (aOR = 3.9, 95% CI =1.24
      12.0). CONCLUSION: Single-dose etomidate for RSI in severely injured trauma
      patients is associated with increased ARDS and multiple organ dysfunction
      syndrome, in part, because of an effect of etomidate on the inflammatory
      response.

PMID- 19590308
TI  - Regional blood flow after serial normovolemic exchange transfusion with HBOC-201
      (Hemopure) in anesthetized swine.
AB  - BACKGROUND: This study determined individual organ blood flows and global
      hemodynamic, oxygen delivery and consumption parameters after normovolemic
      exchange transfusions with the hemoglobin based oxygen carrier (HBOC)-201 in a
      lightly anesthetized swine model. METHODS: The exchange transfusions were
      performed as a stepped reduction in blood volume to attain volume exchanges of
      10%, 30%, and 50% with a 1:1 replacement with HBOC-201 (n = 8) or oncotically
      matched 5.9% human serum albumin (HSA, n = 8). Four additional animals served as
      time controls. RESULTS: There was no change in the regional blood flows in 8 of 9
      organs (brain, heart, kidney, liver, pancreas, gall bladder, small intestines,
      large intestines, and skeletal muscle) after HBOC-201 compared with controls;
      only skeletal muscle blood flow decreased. In contrast, with HSA, blood flow
      increased 150% to 200% of baseline in all organs except muscle where blood flow
      was unchanged. HBOC-201 effectively restored oxygen delivery after these
      exchanges. The mean arterial pressure increases in the HBOC-201 group were within
      15% to 20% of baseline during the initial 10% exchange and similar to controls
      during subsequent exchanges. Although peak pulmonary arterial pressure increases
      in the HBOC-201 group were 10 mm Hg to 15 mm Hg above baseline, cardiac index was
      unchanged. There were no differences in global oxygen consumption, consistent
      with unchanged regional blood flow and suggests intact physiologic coupling of
      oxygen delivery and consumption that was unimpaired by local vasoconstriction.
      This is in contrast to significant changes of increased cardiac index, decreased
      arterial pressure, decreased oxygen content, and increased oxygen extraction
      ratio to maintain normal oxygen consumption in the HSA group. CONCLUSION:
      Although the use of HBOC-201 caused alterations in systemic (minimal) and
      pulmonary (modest) pressures, these changes had no consequence on regional organ
      blood flow.

PMID- 19590309
TI  - Motion of a cadaver model of cervical injury during endotracheal intubation with
      a Bullard laryngoscope or a Macintosh blade with and without in-line
      stabilization.
AB  - BACKGROUND: Endotracheal intubation in patients with potential cervical injury is
      a common dilemma in trauma. Although direct laryngoscopy (DL) with manual in-line
      stabilization (MILS) is a standard technique there is little data on the effect
      of MILS on cervical motion. Likewise there is little data available regarding
      alternative airway techniques in this setting. This study compared intubations
      with and without MILS in a cadaver model of cervical instability. We also used
      this model to compare intubations using DL with a Macintosh blade versus a
      Bullard laryngoscope (BL). METHODS: Complete C4-C5 disarticulations were
      surgically created in 10 fresh human cadavers. The cadavers were then intubated
      in a random order with either BL or DL with and without MILS. The motion at the
      unstable interspace was measured for subluxation, angulation, and distraction.
      RESULTS: MILS did not significantly affect maximal motion of this model in any of
      the three measures using either DL or BL. There were no clinically significant
      differences in maximal median motion in any of the three measures when comparing
      the two blades. However, there was significantly more variance in the subluxation
      caused by DL than by BL. CONCLUSIONS: We were unable to demonstrate any
      significant effect of MILS on the motion of an unstable cervical spine in this
      cadaver model. The BL appears to be a viable alternative to DL in the setting of
      an unstable lower cervical spine.

PMID- 19590310
TI  - Risk factors for mortality in traumatic cervical spinal cord injury: Brazilian
      data.
AB  - BACKGROUND: Predictive factors for mortality are different among countries;
      knowledge of risk factors is important for planning strategies to reduce
      mortality in trauma. The objective of this study was to identify predictors of
      death in traumatic cervical spinal cord injury (TSCI) in Brazil. METHODS: From
      2001 to 2005, 84 patients with clinically detectable TSCI were identified in this
      retrospective study. For each patient, neurologic and associated injuries,
      physiologic variables, complications, treatment, and hospital mortality were
      recorded. Bivariate and multivariate logistic regression analyses were done to
      identify predictors of mortality. RESULTS: Twenty-two (26.2%) patients died in
      hospital. Car crash (39%) and falls (37.85) were the most frequent causes of
      trauma. The causes of death were as follows: neurologic, 8 (36.4%); respiratory,
      4 (18.2%); septic complications, 2 (9.1%); venous thrombosis and embolism, 2
      (9.1%); and undetermined, 4 (18.2%). Bivariate analysis identified absent
      neurologic function (risk ratios [RR] = 4.5; 95% confidence intervals [CI], 1.6
      12.7), high injury severity score (p = 0.001) and low revised trauma score (p =
      0.001); Glasgow Coma Scale (GCS) score <9 (RR = 47.4; 95% CI, 5.4-413.2); shock
      at admission (RR = 2.5; 95% CI, 0.8-7.9); vasopressor use (RR = 25.8; 95% CI, 6.1
      109.6); mechanical ventilation (RR = 31.9; 95% CI, 6.6-154.0); acute renal
      insufficiency (RR = 10.0; 95% CI, 0.98-102.1) as associated with mortality. The
      mainly independents predictors for mortality were GCS score <9 and vasopressor
      use. Lowest mortality rate (5.2%) was observed for patients with TSCI alone.
      CONCLUSIONS: GCS score <9, mechanical ventilation, and vasopressor use were
      predictors of mortality with TCSI, and if these risk factors were absent, we
      observed low mortality rate.

PMID- 19590311
TI  - Evaluation of functionality after head injury in adolescents.
AB  - BACKGROUND: The Occupational Therapy Head Injury Mini Screen (OT HIMS) is a
      screening tool for patients admitted with traumatic brain injury (TBI) in the
      acute care setting. It is a combination of the Galveston Orientation and Amnesia
      Test (GOAT) and the Cognistat (formally the Neurobehavioral Cognitive Status
      Examination). Its purpose is to identify cognitive deficits in patients and to
      provide education for patients on the impact of these deficits on daily living.
      Our hypothesis for this study was that cognitive functionality outcome varies
      with severity of head injury (manifested by Glasgow Coma Scale [GCS]) at
      admission and tests that identify cognitive deficits can be reserved for patients
      admitted with severe head injury. METHODS: Data were prospectively collected for
      all patients with TBI (DRG International Classification of Diseases-9th Rev.
      Clinical Modification codes 800.0-801.99 + 850-859.9), aged 13-21 years, over 10
      years. The inclusion criteria are patients had to be awake and have adequate
      physical function to complete the test. Patients with cognitive deficits were
      identified using GOAT and Cognistat. Preexistent deficits were also identified.
      Scores on OT HIMS were compared with GCS at admission. Outcomes also included
      discharge to home or rehabilitation centers. Hospital deaths were not included in
      the study. RESULTS: Six hundred nine patients were reviewed, and 248 were
      administered the OT HIMS. Eighty-three suffered some impairment. The mean GCS for
      the 248 patients was 13.96 (+/-2.16). A coefficient of correlation between GCS
      and GOAT score of only 0.224 and an R2 value of 0.050 indicated no correlation
      between these results. Comparing GCS and the presence of impairment identified by
      Cognistat yielded an R2 value of 0.093, indicating no correlation between these
      parameters. Among the patients whose results showed cognitive deficits on OT
      HIMS, 38% had impairments before injury. Interestingly, only 58% of patients with
      deficits before injury also demonstrated impairments on OT HIMS. Of the 248
      patients, 12 went to rehabilitation centers and this was not correlated with GCS.
      CONCLUSIONS: In this study, admission GCS did not predict performance on the OT
      HIMS after injury in this cohort of patients with adequate recovery to take the
      examination. Cognitive functionality can be impaired after TBI of even minimal
      degree. All patients admitted for TBI should be screened for cognitive deficits
      before discharge. Long-term follow-up for this group must be performed for
      maximal therapy and optimal outcomes.

PMID- 19590312
TI  - Race?ethnicity and outcome after traumatic brain injury at a single, diverse
      center.
AB  - BACKGROUND: Many factors may predict mortality and disability after traumatic
      brain injury (TBI), including age and injury severity. However, the role of
      race?ethnicity has typically been studied tangentially or in homogeneous
      settings. We investigated whether race?ethnicity was associated with medical
      outcomes at a single, diverse center. METHODS: We retrospectively identified
      patients with TBI older than 17 years with blunt injuries admitted to a Level I
      trauma center from 2001 to 2004. Glasgow Outcome Scale (GOS) was used to
      determine outcome at discharge. We performed multivariable logistic regression on
      two measures of outcome by dichotomizing Glasgow Outcome Scale scores. RESULTS:
      We identified 357 patients with TBI from five categories: whites (46.2%), Asians
      (19.9%), Hispanics (17.9%), blacks (10.9%), and other?unknown (5.0%). Without
      adjusting for other factors, Asians experienced higher mortality (odds ratio [OR]
      = 2.25, p = 0.01) compared with whites but not degree of disability. After
      adjusting for age and Injury Severity Score, a weaker trend remained for higher
      mortality in Asians (OR = 1.38, p = 0.35), and after excluding cases of assault,
      the finding was again significant (OR = 2.00, p = 0.04). We also confirmed the
      recently reported OR of higher mortality among blacks (OR = 1.30). Hispanics
      seemed to do slightly better at discharge. CONCLUSIONS: The question of whether
      and how race plays a role in TBI is controversial. At a single, diverse center,
      we found that mortality is associated with race, age, and Injury Severity Score.
      Future clinical studies will benefit from detailed genotypic and phenotypic data
      and should balance larger sample sizes with ethnic diversity.

PMID- 19590313
TI  - Prospective evaluation of a predictive model of mortality in patients with
      isolated head injury.
AB  - BACKGROUND: In a previous retrospective study, we developed a predictive model of
      survival in isolated head injuries based on easily available parameters such as
      age, mechanism of injury, Glasgow Coma Scale, and head Abbreviated Injury Scale
      (AIS). The purpose of the present study is to prospectively evaluate this
      predictive model. METHODS: Isolated head injuries admitted to a Level I urban
      trauma center were prospectively accrued from May 1, 2006 through April 30, 2007.
      Age, mechanism of injury, Glasgow Coma Scale, head AIS, and survival status were
      recorded for each patient. Patients with extracranial AIS >3, head AIS = 6, or
      hypotension were excluded. These data were entered into our previously developed
      predictive model and the percentage of correct classification was used to measure
      how well the predictive model predicted outcome. Sensitivity, specificity,
      positive and negative predictive values, and their 95% confidence intervals were
      calculated and compared with values obtained from our original, retrospective
      study. RESULTS: Seven hundred eighty-six patients met the criteria for inclusion
      in the study with an overall mortality of 5.8% (46 patients). When entered into
      our predictive model, the percentage of correct classification rate was 92%
      compared with the 94% rate seen in the original study, which is better than other
      available predictive tools based on combined scoring systems such as the Trauma
      and Injury Severity Score methodology. CONCLUSION: When evaluated prospectively,
      our predictive model has similar accuracy in predicting survival of all patients
      with head trauma as our original retrospective study and performs better than
      other predictive models such as the Trauma and Injury Severity Score methodology.
      This study demonstrates that a simple table based on easily obtained admission
      patient characteristics can rapidly provide information about the probability of
      survival in patients with head injuries.

PMID- 19590314
TI  - Mortality in severe traumatic brain injury: a multivariated analysis of 748
      Brazilian patients from Florianopolis City.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of incapacity and
      mortality worldwide, with most of the burden occurring in low-income and middle
      income countries. A number of clinical, demographic, and neurosurgical variables
      of patients with TBI were associated with their outcome. METHODS: We investigated
      the mortality of Brazilian patients with severe TBI at the time of discharge,
      using a multiple logistic regression analysis. Clinical, demographic, radiologic,
      and neurosurgical variables, and mortality at time of discharge of all
      consecutive patients (n = 748) with severe TBI (admission Glasgow scale < or = 8)
      treated in our intensive care unit were analyzed. The variables were collected in
      a prospective manner between January 1994 and December 2003. RESULTS: Eighty-four
      percent (n = 631) of the patients were men. The mean age was 34.8 (+/-16.3) years
      and the mortality was 33.3%. After the multiple logistic regression, the adjusted
      odds ratio (OR) for death was higher in older (> 60 years) than younger (up to 30
      years) patients (OR = 2.51, 95% confidence interval [CI] 1.31-4.79, p = 0.006).
      The mortality was also associated with sub-arachnoid hemorrhage (OR = 1.86, 95%
      CI = 1.23-2.81, p = 0.003) on computed tomography (CT) scan; admission Glasgow
      Scale of 3 or 4 in comparison to 7 or 8 (OR = 3.97, 95% CI = 2.49- 6.31, p <
      0.001); bilateral midryasis (OR = 11.52, 95% CI = 5.56-23.87, p < 0.0001), or
      anisocoria (OR = 2.65, 95% CI = 1.69-4.17, p < 0.0001) in comparison to isocoric
      pupils. There was a trend for higher mortality in patients with type III injury
      on the Marshall classification of CT (OR = 3.63, 95% CI = 0.84-15.76, p = 0.08)
      than in patients with normal CT. Patients without thoracic trauma disclose higher
      mortality than patients with associated thoracic trauma do (OR = 2.02, 95% CI =
      1.19-3.41, p = 0.009). The final model presented disclosed 76.9% of overall
      correct prediction with the survival and death predicted at 87.6% and 55.6%,
      respectively. CONCLUSION: Age, CT findings, Glasgow coma scale, pupil
      examination, and the presence of thoracic trauma at admission were independently
      associated with mortality at the time of discharge in Brazilian patients with
      severe TBI.

PMID- 19590315
TI  - Risk factors for relapse of ventilator-associated pneumonia in trauma patients.
AB  - BACKGROUND: Our goal was to define risk factors for ventilator-associated
      pneumonia (VAP) relapse and examine the implications, if any, for initial therapy
      in trauma patients. METHODS: Trauma patients cared for in the surgical intensive
      care unit during a 48-month period with confirmed VAP recurrence were evaluated.
      Recurrent VAP was defined as a positive quantitative culture (> or = 10(4) colony
      forming units/mL in a bronchoalveolar lavage or protected catheter lavage
      specimen) > or = 4 days after initiation of antibiotics for the primary episode.
      Recurrence with at least one of the initial causative pathogens was defined as a
      relapse. Initial causal pathogen, Acute Physiology and Chronic Health Evaluation
      II score, injury severity score, Glasgow Coma Score (GCS), age, white blood cell
      count (WBC), and duration of hospital stay before diagnosis were analyzed in
      univariate and multivariate regression models. RESULTS: A total of 55 patients
      met the criteria of recurrent VAP. Of these 55 recurrences, 19 (35%) were
      relapses. Acute Physiology and Chronic Health Evaluation II score, injury
      severity score, and GCS were not associated with VAP relapse by univariate
      analyses. Patients who relapsed had primary VAP involving nonfermenting gram
      negative bacilli (NFGNB) (Acinetobacter, Pseudomonas, and Stenotrophomonas
      species) more frequently than other organisms (68% vs. 32%, p = 0.001). Primary
      VAP with NFGNB was found to be a significant predictor of VAP relapse by
      univariate and multivariate logistic regression analysis (OR = 5.1, p = 0.003; OR
      = 4.63, p = 0.005, respectively). CONCLUSIONS: There is a high rate of VAP
      relapse associated with primary infection by NFGNB, suggesting initial treatment
      failure. Trauma patients with primary VAP involving these organisms may benefit
      from increased surveillance for relapse.

PMID- 19590316
TI  - Transfusion and pneumonia in the trauma intensive care unit: an examination of
      the temporal relationship.
AB  - BACKGROUND: Transfusion has been demonstrated to be associated with pneumonia in
      injured patients, and blood of older storage age may potentiate this morbidity.
      It remains unclear, however, whether this association is causal, as prior studies
      have not accounted for prepneumonia versus postpneumonia transfusion. We sought
      to evaluate the temporal relationship between transfusion and pneumonia and the
      influence of blood age on this relationship. METHODS: Admissions to a Level I
      trauma center between July 2004 and October 2007 with the following
      characteristics were selected for inclusion: overall length of stay of > or = 4
      days; intensive care unit length of stay of > or = 1 day; and > or = 1 ventilator
      days. Date(s) of transfusion and blood storage age defined as "old" > or = 14
      days and "young" < 14 days were obtained. Pneumonia was diagnosed by
      bronchoalveolar lavage (> 10(5) colonies/mL). Risk ratios (RR) and 95% confidence
      intervals (CIs) were calculated for the association between pneumonia and both
      date (in relation to pneumonia) and age of blood transfused, adjusted for age,
      gender, injury severity, mechanism of injury, ventilator days, and transfusion
      volume. RESULTS: A total of 1,615 patients met study criteria. Adjusted RR (CI)
      for the association between pneumonia and receipt of blood at any time was 1.99
      (1.39-2.86). However, when postpneumonia transfusions were disregarded, no
      association was observed (RR 1.33; CI 0.98-1.80). Analysis by blood age, however,
      demonstrated that prepneumonia transfusion of exclusively older blood was
      significantly associated with an increased risk of pneumoinia (adjusted RR 1.42;
      CI 1.01-2.02), whereas transfusion of exclusively younger units (adjusted RR
      1.02; CI 0.62-1.67) or mixed units (adjusted RR 1.35; CI 0.98-1.87) were not.
      CONCLUSIONS: Prior reports of an association between transfusion and pneumonia
      may reflect transfusions received after pneumonia rather than etiologically
      relevant transfusions received before the onset of pneumonia. Transfusion of
      exclusively older blood, however, increased the risk of pneumonia, further
      suggesting the importance of blood age with respect to outcomes in trauma
      patients.

PMID- 19590317
TI  - The incidence and complications of methicillin-resistant Staphylococcus aureus in
      a community Level I trauma center.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a growing cause
      of infections among hospitalized trauma patients. We examined the incidence and
      infectious consequences of MRSA among trauma patients admitted to our Level I
      Trauma Center during 24 months. METHODS: Nasal swab cultures were obtained at
      admission and on hospital day 5. Patient demographics and infectious
      complications were recorded and compared. Differences with p values less than
      0.05 were considered significant. RESULTS: Admission MRSA screening was positive
      in 71 patients, yielding a carrier prevalence rate of 5.8% (95% CI 4.5-7.1%). No
      admission characteristic was associated with positive MRSA screening. Twelve
      patients (1.7%, 95% CI 0.7-2.6%) who were MRSA negative at admission tested
      positive for MRSA on hospital day 5. The clinical MRSA infection incidence rate
      was 1.4% (95% CI 0.7-2.0%). The screening test for MRSA at admission demonstrated
      a sensitivity of 23.5% (95% CI 6.8-49.9%) and specificity of 94.5% (95% CI 93
      95.7%) for predicting MRSA infection. MRSA infections were associated with
      increased lengths of stay: intensive care unit 17.7 versus 5.1 days, p < 0.001,
      hospital 23.1 versus 8.6 days, p < 0.001. CONCLUSIONS: MRSA infections affect a
      minority of our trauma patients yet prolong length of stay. Admission MRSA
      screening of trauma patients does not sufficiently identify patients at risk for
      infectious complications and should not be practiced.

PMID- 19590318
TI  - Impact of obesity in damage control laparotomy patients.
AB  - BACKGROUND: Obesity is an independent predictor of increased morbidity and
      mortality in critically injured trauma patients. We hypothesized that obese
      patients in need of damage control laparotomy (DCL) will encounter an increase
      incidence of postsurgical complications with a concomitant increase mortality
      when compared with a cohort of nonobese patients. METHODS: All adult trauma
      patients who underwent DCL during a 4-year period at a Level I Trauma Center were
      retrospectively reviewed. Patients were categorized into nonobese (body mass
      index [BMI] < or = 29 kg/m), obese (BMI 30-39 kg/m), and severely obese (BMI > or
      = 40 kg/m) groups. Outcome measures included the occurrence of postoperative
      infectious complications, failure of primary abdominal wall fascial closure,
      acute respiratory distress syndrome, acute renal insufficiency, multiple system
      organ failure, days of ventilator support, hospital length of stay, and death.
      RESULTS: During a 4-year period, 12,759 adult trauma patients were admitted to
      our Level I Trauma Center of which 1,812 (14.2%) underwent emergent laparotomy.
      Of these, 104 (5.7%) were treated with DCL: nonobese, n = 51 (49%); obese, n = 38
      (37%); and severely obese, n = 15 (14%). In a multivariate adjusted model,
      multiple system organ failure was 1.82 times more likely in severely obese (95%
      CI: 1.14-2.90) and 1.74 times more likely in the obese patients (95% CI: 1.14
      2.66) when compared with patients with normal BMI after DCL (p < 0.01). In the
      severely obese patients undergoing DCL, significantly elevated prevalence ratios
      (PR) for development of postoperative infectious complications, acute renal
      insufficiency, and failure of primary abdominal wall fascial closure were 1.75,
      3.07, and 2.62, respectively. Days of ventilator support, length of stay, and
      mortality rates were significantly higher in severely obese patients (24 days, 27
      days, and 60%) compared with obese (14 days, 14 days, and 21%) and nonobese (9.8
      days, 14 days, and 28%) patients. CONCLUSION: Severe obesity was significantly
      associated with adverse outcomes and increased resource utilization in trauma
      patients treated with DCL. Measures to improve outcomes in this vulnerable
      patient population must be directed at multiple levels of health care.

PMID- 19590319
TI  - Clinical significance of plasma ammonia in patients with traumatic hemorrhage.
AB  - BACKGROUND: Hemorrhagic shock has been reported to elevate the concentration of
      ammonia in the blood of animals. However, only one clinical study, of a few
      surgical patients, found a similar effect. This investigation sought to determine
      whether ammonia is elevated in the plasma of trauma patients with hemorrhage and
      whether it could be used to predict serious hemorrhage. METHODS: Subjects were
      consecutive trauma patients admitted to our Level I trauma center between
      November 2006 and April 2008 who met the inclusion criteria to determine plasma
      ammonia. Their blood was sampled at admission. Patients who required blood
      transfusion > or = 2 U or intervention for bleeding within 24 hours were
      classified into a bleeding group. Patients who did not require a transfusion or
      interventions were classified as controls. In addition to routine hemodynamic
      measurements, we recorded the hourly infused volume of Ringer's lactate solution
      (infusion volume) during emergency room treatment and total transfused blood
      volume within the first 24 hours. RESULTS: The subjects were 282 trauma patients.
      Their mean age was 44.0 +/- 20.4 years old, and their mean injury severity score
      was 15.8 +/- 13.1. Ammonia was significantly correlated with systolic blood
      pressure, shock index at admission, infusion volume, base deficit, and injury
      severity score. Forty-one patients required blood transfusion and 31 needed
      intervention for arterial bleeding. Because some patients required both
      therapies, the bleeding group consisted of 46 patients. The control group
      consisted of 236 patients who needed neither blood transfusion nor intervention.
      The plasma ammonia concentration in the bleeding group (113 +/- 52.2 microg/dL)
      was significantly higher than in the control group (55.4 +/- 20.8 microg/dL). In
      the bleeding group, the ammonia concentration of patients who died from bleeding
      (170 +/- 68.7 microg/dL) was significantly higher than in survivors (102 +/- 40.7
      microg/dL). The best ammonia concentration cutoff value that maximized
      sensitivity and specificity to select for the bleeding group was > or = 77
      microg/dL (sensitivity, 82%; specificity, 89%). CONCLUSIONS: Elevated plasma
      ammonia concentration at admission can be a clinically significant indicator for
      traumatic hemorrhage that requires treatment.

PMID- 19590320
TI  - Reticulocyte counts and their relation to hemoglobin levels in trauma patients.
AB  - BACKGROUND: Increased production of red blood cells (RBCs) should be reflected by
      increased reticulocyte counts (RC). With the introduction of modern fully
      automated measurements of RC, the recovery of hemoglobin (Hb) after blood loss
      might be assessed earlier. We investigated the temporal relation of Hb and RC in
      trauma patients. METHODS: Over a 10-month period, all patients with trauma
      admitted to our University Medical Center were analyzed. Both Hb (reference
      values: males, 14.0-17.1 g/dL; females, 12.1-15.9 g/dL) and RC (8-26 promille)
      were determined with a Sysmex XE-2100 analyzer. RBC transfusions were
      administered in otherwise healthy patients below an Hb threshold of 6.9 g/dL. Hb
      and RC were analyzed for a maximum of 30 days posttrauma and related in
      multivariate analysis to age, sex, and comorbidity. RESULTS: Two hundred and
      forty-one patients (age 52 years +/- 21 years) were studied. In 28 patients
      (12%), one or more RBCs were administered with a mean of 2.2 RBCs (range, 1-4).
      Hb decreased to 10.9 g/dL +/- 2.1 g/dL on day 3. RC rose from 16 +/- 11 at
      admission to 38 promille +/- 21 promille on day 13 (p < 0.0001). Nadir Hb values
      and maximum RC values were inversely related according to univariate analysis
      (Pearson R = -0.62, p < 0.001). In multivariate analysis, Hb remained the only
      significant determinant of RC (R = 0.64, p < 0.001). CONCLUSIONS: Hb and RC are
      clearly related in trauma patients. Measuring RC may be helpful in predicting the
      rise of Hb after acute blood loss.

PMID- 19590321
TI  - Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns
      and prognostic value of thrombelastometry.
AB  - BACKGROUND: The aim of this study was to diagnose hyperfibrinolysis (HF) and its
      pattern using thrombelastometry and to correlate the diagnosis with mortality.
      Furthermore, routine laboratory based and the rotational thrombelastometry
      analyzer (ROTEM)-derived variables were also correlated with survival. METHODS:
      Severe trauma patients showing HF in ROTEM were consecutively enrolled in the
      study. Three different HF patterns were compared: fulminant breakdown within 30
      minutes, intermediate HF of 30 to 60 minutes, and late HF after 60 minutes.
      Injury severity score (ISS), hemodynamics, hemoglobin, hematocrit, platelet count
      (PC), fibrinogen, and ROTEM variables at admission were analyzed. The observed
      mortality was compared with the predicted trauma and injury severity score
      mortality. RESULTS: Thirty-three patients were diagnosed with HF. The mean ISS
      was 47 +/- 14. Fulminant, intermediate, or late HF (n = 11 each group) resulted
      in 100%, 91%, or 73% mortality, respectively, with the best prognosis for late HF
      (p = 0.0031). The actual overall mortality of HF (88%) exceeded the predicted
      trauma and injury severity score mortality (70%) (p = 0.039). Lower PC (123 +/-
      53 vs. 193 +/- 91; p = 0.034), ROTEM prolonged clot formation time [CFT, 359
      (140/632) vs. 82 (14/190); p = 0.042], and lower platelet contribution to maximum
      clot firmness [MCF(EXTEM) - MCF(FIBTEM), 34 (20/40) vs. 46 (40/53); p = 0.026]
      were associated with increased mortality. CONCLUSION: ROTEM-based diagnosis of HF
      predicted outcome. Further independent predictors of death were combination of HF
      with hemorrhagic shock, low PC, and prolonged CFT in ROTEM. ROTEM-based point of
      care testing in the emergency room is thus able to identify prognostic factors
      such as prolonged CFT and low platelet contribution to clot firmness (MCF(EX) -
      MCF(FIB)) earlier than standard laboratory-based monitoring.

PMID- 19590322
TI  - Pentobarbital reduces rhabdomyolysis-induced acute renal failure in conscious
      rats.
AB  - BACKGROUND: Rhabdomyolysis is one of the causes of acute renal failure.
      Pentobarbital enhances the action of gamma-aminobutyric acid and suppresses the
      activities of nuclear factor (NF)-kappaB pathways. In this study, we used
      pentobarbital to study the effects on the glycerol-induced rhabdomyolysis with
      acute renal failure in conscious rats. METHODS: Rhabdomyolysis was induced by
      intramuscular injection of 10 mL/kg of 50% glycerol in conscious rats. Ten
      minutes later, the rats received an intravenous injection of pentobarbital (10
      mg/kg in 0.5 mL/h normal saline) or normal saline (0.5 mL/h). Biochemical
      substances, including blood urea nitrogen (BUN), creatinine (Cre), glutamic
      oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine
      phosphokinase (CPK) were measured at 0 hour, 1 hour, 3 hours, 6 hours, 12 hours,
      24 hours, and 48 hours. Rats were killed by decapitation at 48 hours after
      glycerol administration, and the kidneys were removed immediately for
      pathological findings and immunohistochemistry. RESULTS: Intramuscular injection
      of glycerol significantly increased blood BUN, Cre, GOT, GPT, CPK levels and
      induced severe histopathologic damage in the kidneys. NF-kappaB and inducible
      nitric oxide synthase (iNOS) were increased, and E-cadherin was decreased after
      glycerol administration, as detected by immunohistochemistry in the kidneys.
      Posttreatment with pentobarbital decreased blood BUN, Cre, GOT, GPT, CPK levels,
      decreased the markers of kidney injury, and suppressed the release of NF-kappaB
      and iNOS after rhabdomyolysis. CONCLUSION: Posttreatment with pentobarbital
      suppressed the activities of NF-kappaB and iNOS, decreased BUN, Cre, GOT, GPT,
      CPK levels, and decreased the markers of kidney injury after rhabdomyolysis.
      These actions ameliorated rhabdomyolysis-induced acute renal failure in conscious
      rats.

PMID- 19590323
TI  - Close range gun shot injuries of the hand with the "mole gun".
AB  - INTRODUCTION: A mole gun is a handmade weapon used as a trap to kill moles by
      farmers. Their action is based on a simple hammer mechanism: when the moles put
      their head through the metal ring to get hold of the food, they trigger the
      mechanism. The hammer strikes the primer, which ignites the gunpowder, propelling
      the pellets from the barrel. The purpose of this study was to report our
      experiences in a group of patients who accidentally suffered injuries by mole
      guns to the hand. METHOD: Since 2000, 20 patients had attended the clinic with
      mole gun shot injuries to the hand. RESULTS: The mean age of patients was 38
      years. Thirteen cases involved skin defects over the dorsum of the hand
      associated with extensor tendon and bone injuries. The skin defect was covered
      with posterior interosseous artery (PIA) flap in 12 cases. In one case, the PIA
      pedicle was found to be injured so radial forearm flap was used. The main
      intervention time for these cases was 6.2 days. All flaps except two PIA flap
      survived uneventfully. One flap was completely lost while other survived with
      distal necrosis. In remaining seven cases the thumb was the main injured part; it
      had complete disruption of its arterial supply and was managed with amputation
      with or without matarcarpal removal. These cases were managed immediately.
      CONCLUSION: The risk of injury to the PIA by pellets is low in such close range
      shots to the hand and PIA flap could be used to cover the defects. In such cases,
      initial debridement should be minimal and the soft tissue, tendon, and bone
      injury can be managed in the same stage during the first week of injury.

PMID- 19590324
TI  - The long-term outcome of open reduction and internal fixation of stable displaced
      isolated partial articular fractures of the radial head.
AB  - BACKGROUND: Excellent long-term results have been reported for nonoperative
      treatment of stable isolated displaced partial articular (Mason 2) fractures of
      the radial head, suggesting that the role of operative treatment can be
      questioned. This investigation reports the long-term outcome of operatively
      treated Mason 2 radial head fractures. METHODS: Sixteen patients with stable
      displaced partial articular (Mason 2) fractures of the radial head not associated
      with fracture or dislocation of the proximal forearm were evaluated an average of
      22 years (range, 14-30 years) after open reduction and internal fixation with
      screws (11 patients) or a plate and screws (5 patients). Complications included
      two infections (1 deep and 1 superficial), two patients with restriction of
      motion because of screws of excessive length, and one transient posterior
      interosseous nerve palsy. A second surgery for implant removal was routine (14 of
      16 patients). RESULTS: The average flexion arc was 129 degrees (range, 110-145
      degrees) and the average forearm rotation arc was 166 degrees (range, 120-180
      degrees). According to the Mayo Elbow Performance Index, elbow function was
      excellent in nine patients, good in four, fair in two, and poor in one patient.
      According to the classification system of Steinberg et al., there were three
      good, eight fair, and five poor results. The average score on the Disabilities of
      the Arm, Shoulder, and Hand questionnaire was 12 points (range, 0-52).
      CONCLUSION: The long-term results of operative treatment of stable isolated
      displaced partial articular (Mason 2) fractures of the radial head demonstrate no
      appreciable advantage over the long-term results of nonoperative treatment of
      these fractures published in prior reports. Moreover, the appeal of operative
      treatment is diminished by the potential complications.

PMID- 19590325
TI  - When violence strikes the head, neck, and face.
AB  - INTRODUCTION: The aim of this study was to find characteristics in head-neck
      facial (HNF) injuries among victims of violence and to test the hypothesis that
      the type of injury, location, and mechanism behind it vary between the genders.
      METHODS: A 1-year prospective study including all victims of violence attending
      the Accident & Emergency (A&E) Department or the Institute of Forensic Medicine
      in Aarhus was conducted. Every violence-related injury was recorded along with
      the mechanism behind it, the type of injury, and the specific anatomic location.
      RESULTS: A total of 1,106 victims were examined of whom 83% had HNF injuries.
      Thirty-seven percent had more than one HNF injury. Injuries around the nose and
      mouth were significantly associated with male victims, whereas injuries to the
      neck were significantly more common among female victims. Most injuries were the
      results of assault with a blunt object, where the men much more frequently had
      open wounds, whereas injuries such as ecchymoses were significantly more frequent
      among female victims. Use of weapons, such as blunt objects and blows with
      glass/bottles, was associated much more with male victims, whereas strangulation
      attempts were significantly more frequent among women. Ten percent of the women
      had been exposed to strangulation attempts. DISCUSSION: The findings support
      former studies that HNF injuries might be considered as markers of violence.
      Thus, the staff at A&E Departments must consider anyone with these types of
      injuries as potential victims of violence. The A&E Department may be the primary
      entrance for the victims and the main way in which to offer help. The high
      incidence of women who had been assaulted with strangulation, which is a
      potentially very dangerous trauma mechanism, intensifies the importance of
      conducting a careful medical examination, in part, because of the possible legal
      implications. CONCLUSION: HNF injuries are characteristic among victims of
      violence, although significant differences exist in the type of injuries, the
      location, and the trauma mechanism between men and women.

PMID- 19590326
TI  - Diagnosis of penetrating injuries of the pharynx and esophagus in the severely
      injured patient.
AB  - BACKGROUND: Diagnosis of penetrating pharyngeal and esophageal injuries are
      difficult when the patient has severe facial injuries, is obese or intubated, and
      hemodynamically unstable. Radiologic aids may be either unsuitable or unreliable.
      Videoendoscopy, preferably by the trauma surgeon, affords direct visualization at
      the bedside and is timely and expeditious. METHODS: Patients included in the
      study had penetrating injuries to the face/neck or torso. Evaluation began with
      careful assessment of the trajectory, followed by videoendoscopy and a contrast
      study. Data collected included the accuracy of diagnosis (compared with anatomic
      findings), time required to perform the studies, and complications resulting from
      both tests and repair. RESULTS: Thirty-three patients were included in the study.
      Contrast study detected all esophageal injuries, but failed to detect any
      hypopharyngeal injuries particularly in the intubated patients. Videoendoscopy
      detected all injuries, hypopharyngeal and esophageal in intubated and
      nonintubated patients. CONCLUSIONS: Radiologic studies should not be used for
      pharyngeal injuries. Although radiologic studies accurately diagnosed penetrating
      injuries of the esophagus, it is not as expeditious as videoendoscopy performed
      by the trauma surgeon. Videoendoscopy should be part of the trauma surgeons'
      armamentarium.

PMID- 19590327
TI  - Long-term outcome of conservatively managed displaced acetabular fractures.
AB  - BACKGROUND: The purpose of this study was to determine the long-term outcome of
      conservatively managed acetabular fractures involving the weight-bearing dome,
      which otherwise deserves an operative treatment. METHODS: Thirty-two patients
      with displaced acetabular fractures (>3 mm displacement) involving the weight
      bearing dome and not associated with unstable pelvic ring injuries met the
      inclusion criteria for this study with a minimum of 2 years of follow-up
      evaluation. They were assessed using the Merle de'Aubigne and Postel clinical
      scoring and Matta's radiologic scoring system. The mean duration of follow-up was
      4.1 years (2-12 years). RESULTS: The reducibility of acetabular fractures by
      conservative management stood at 18 of 32 (56.3%) synchronizing with 18 of 32
      (56.3%) good to excellent clinical score. The mean clinical score was 14.25 +/-
      3.41 of a total score of 18. In patients with good fracture reduction, good to
      excellent results were seen in 83.3% cases. The radiologic grade was good to
      excellent in 50% cases with good clinicoradiologic correlation (p = 0.0001).
      CONCLUSIONS: Acetabular fractures involving the weight-bearing dome if reduced by
      closed means can be maintained by heavy lateral and longitudinal traction
      resulting in good clinicoradiologic outcome comparable with operative management.

PMID- 19590328
TI  - Differences in prescription of narcotic pain medication after operative treatment
      of hip and ankle fractures in the United States and The Netherlands.
AB  - BACKGROUND: Interactions between American and Dutch surgeons suggested
      differences in prescription habits for pain medication after fracture treatment.
      METHODS: The percentages of 190 American [100 after hip open reduction and
      internal fixation (ORIF) and 90 after ankle ORIF] and 116 Dutch patients (69
      after hip ORIF and 47 after ankle ORIF) receiving inpatient and outpatient
      prescriptions for narcotics were retrospectively compared between countries, to
      test the hypothesis that narcotics are prescribed more frequently in the United
      States as compared with The Netherlands after operative fracture treatment.
      RESULTS: Among patients with hip fractures, 85% of American and 58% of Dutch
      patients were prescribed narcotics during hospitalization (p < 0.001). After
      discharge, 77% of American and none of the Dutch patients were prescribed
      narcotics (p < 0.001). The multivariate model including country accounted for 11%
      of the variation in inpatient narcotic prescription (p < 0.001), and the model
      including country and surgeon accounted for 55% of the variation in outpatient
      narcotic prescription (p < 0.001). Among patients with ankle fracture, 98% of
      American and 64% of Dutch patients were prescribed narcotics during
      hospitalization (p < 0.001). After discharge, 82% of American patients and 6% of
      Dutch patients were prescribed narcotics (p < 0.001). Predictors included country
      and surgeon and they accounted for 20% of the variation in inpatient narcotics
      prescription (p < 0.001) and 49% of the variation in outpatient narcotic
      prescription (p < 0.001). CONCLUSIONS: American patients are prescribed
      significantly more inpatient and outpatient narcotic pain medication than Dutch
      patients after operative treatment of hip and ankle fractures.

PMID- 19590329
TI  - Osteogenesis of prefabricated vascularized periosteal graft in rabbits.
AB  - BACKGROUND: The role of vascularized periosteum flap as a graft and the factors
      stimulating it into osteogenic activity remain obscure. Few articles recognized
      its osteogenic process without the dependence of stress stimulation or bony
      contact. METHODS: We analyzed the osteogenic capacity of the vascularized
      periosteum in an ectopic site via the method of histomorphologic assessment.
      Pedicled vascularized periosteum was taken from the proximal tibia in rabbits and
      transferred to the soft tissue pouch in the distal thigh. Specimen was harvested
      for osteogenesis assessment at 4 weeks, 8 weeks, and 16 weeks. RESULTS: During
      macroscopic examination, all rabbits were dissected along the previous surgical
      wound in the distal femur. Dense osseous-like tissue was found in the
      prefabricated vascularized periosteum. The tissue sections showed red-mineralized
      matrix of Alizarin Red S staining increased neovascularization. CONCLUSIONS: The
      study results revealed the osteogenic capacity of prefabricating vascularized
      periosteum without the dependence of stress stimulation or its proximity to
      viable bone.

PMID- 19590330
TI  - Injury patterns of female homicide victims in South Africa.
AB  - BACKGROUND: Injury patterns and interpretation of injuries in homicidal deaths
      are important components of medicolegal autopsies. The objective of this article
      is to describe the incidence of female homicides and their related injury
      patterns with reference to autopsy practices in South Africa. METHODS: A national
      retrospective mortuary-based study of homicides in women of 14 years and older in
      1999 was conducted. Data were gathered from medical legal laboratory records,
      autopsy reports, and police interviews from a stratified multistage sample of 25
      mortuaries. RESULTS: The most common cause of homicide was a gunshot wound
      injury, with a firearm mortality rate of 7.5/100,000 women, 14 years and older,
      in 1999, followed by sharp force injury (6.8/100,000) and blunt force injury
      (6.1/100,000). Gunshot victims were more likely to be African, and those killed
      by sharp force injury were more likely colored. Significantly, blunt force injury
      deaths occurred predominantly in intimate partner homicides. A full autopsy was
      performed only in 70% of cases. An assessment of postmortem reports revealed poor
      descriptions of the anatomic location of injuries and the specifications of wound
      dimensions. CONCLUSIONS: South Africa has a high female homicide rate that
      exceeds reported rates with the cause of homicide varying by social group.
      Assessment of injury description suggests weaknesses in the documentation of
      injuries at autopsy. This weakens the forensic investigation and undermines the
      strength of evidence presented in court. Further measures are needed to
      strengthen forensic pathology services in South Africa.

PMID- 19590331
TI  - Uncovering system errors using a rapid response team: cross-coverage caught in
      the crossfire.
AB  - BACKGROUND: Because of the 80-hour work week, extensive service cross-coverage
      creates great potential for patient care errors. These patient care emergencies
      are increasingly managed using a rapid response team (RRT) to reduce patient
      morbidity. We examine the proximate causes of a surgical RRT activation. We
      hypothesize that most RRTs would occur during cross-coverage hours and be
      preventable or potentially preventable. METHODS: All surgical RRTs more than a 15
      month period were captured using a nursing database and the note from the
      staffing intensivist/fellow. RRTs were reviewed for appropriateness (pre-existing
      criteria) and proximate cause. Proximate causes were further classified as
      patient disease, team error, nursing error, or system error as well as
      preventable, potentially preventable, or nonpreventable. RESULTS: Of 98 RRT
      activations, complete data were available for 82 (84%); 100% met activation
      criteria; and 76 (93%) occurred between 2100 and 0600. Seventy-six patients were
      48 hours to 72 hours postoperative; six had nonoperatively managed injuries. The
      most common reason for activation was impending respiratory failure and acute
      volume overload (n = 72; 88%). RRT therapies included diuretics (n = 72),
      antiarrhythmics (n = 48), oxygen (n = 82), and bronchodilators (n = 36); only 2
      received blood component therapy. Seventy-eight patients (95%) were transferred
      to higher level of care (61, surgical intensive care unit; 17, SSDU). Only 46% of
      patients required intubation. Performance improvement review identified 90% of
      physician related RRTs as preventable/potentially preventable because of errors
      in judgment or omission. Four RRTs because of patient disease were unpreventable.
      Two potentially preventable errors were each ascribed to RN or system concerns.
      CONCLUSION: RRT activations principally result from team-based errors of
      omission, more often occur between 2100 and 0600, and are more often preventable
      or potentially preventable. Careful attention to fluid balance and medications
      for comorbid diseases would reduce RRT needs.

PMID- 19590332
TI  - Surgical trauma referrals from rural level III hospitals: should our community
      colleagues be doing more, or less?
AB  - BACKGROUND: Rural citizens die more frequently because of trauma than their urban
      counterparts. Skill maintenance is a potential issue among rural surgeons because
      of infrequent exposure to severely injured patients. The primary goal was to
      evaluate the outcomes of multiple injuries patients who required a laparotomy
      after referral from level III trauma centers. METHODS: All severely injured
      patients (injury severity score >12) referred to a level I trauma center from
      level III hospitals, during a 48-month period were evaluated. Comparisons between
      referrals (level III and IV) as well as survivors and nonsurvivors used standard
      statistical methodology. RESULTS: One thousand two hundred and thirty patients
      (35%) were transferred from level III (33%) and level IV (67%) centers (43%
      underwent an operative procedure). Only 13% required a laparotomy, whereas 87%
      needed procedures from other subspecialists. Referred patients had a mean injury
      severity score of 28, length of stay of 28 days, and mortality rate of 26%. More
      patients arrived hemodynamically unstable from level IV (55%) versus level III
      (35%) hospitals (p < 0.05). Nonsurvivors from level III centers were more likely
      to transfer via aircraft (100%) than from level IV hospitals (55%) (p < 0.05).
      Most (91%) definitive general surgery procedures could have been completed by
      surgeons at level III centers; however, 90% also had multisystem injuries
      requiring treatment by other subspecialists. CONCLUSIONS: Most severely injured
      patient referrals from level III and IV trauma centers in Western Canada are
      appropriate. The lack of consistent subspecialty coverage mandates most transfers
      from level III hospitals. This data will be used to engage rural Alberta
      physicians in an educational outreach program.

PMID- 19590333
TI  - Application of International Classification Injury Severity Score to National
      Surgical Quality Improvement Program defines pediatric trauma performance
      standards and drives performance improvement.
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program is becoming a core methodology to define performance as a
      ratio of observed to expected events. We hypothesized that application of this
      using International Classification of Injury Severity Score (ICISS) for
      individual patient risk stratification to a group of hospitals contributing data
      to the National Pediatric Trauma Registry (NPTR) would apply objective evidence
      of actual injuries to define an expected standard and identify performance
      outliers. METHODS: Using a blinded code, children entered into phase III of the
      NPTR were aggregated by treating hospital. Individual patient ICISS survival
      probability (Ps) were calculated using survival risk ratios (SRR) derived from
      the phase II NPTR dataset (n = 53,253). For each center, sample size, observed
      mortality, and ICISS Ps were calculated. Probability of mortality (Pm) was
      computed as 1 - Ps. Logistic regression was used to develop a predictive model
      for mortality. Logit transformation of Pm was performed to adjust for the skew of
      minor injury in children and reduce overestimation of low Pm fatalities. Mean Pm
      was computed for each center and multiplied by its volume to determine expected
      frequency. Observed to expected ratio (O/E) and 95% confidence interval were
      calculated to define expected performance and outliers above or below 1 SD of the
      mean O/E. RESULTS: Patients treated at 30 pediatric trauma centers (mean volume =
      451 +/- 258/patients per center) were evaluated. Mean O/E was 1.001 with SD =
      0.404. Twenty-two centers fell within the reference range; O/E of 12 centers
      exceeded 1, suggesting performance below expectation. Trauma center volume, as
      reflected by sample, did not correlate to O/E performance. CONCLUSIONS:
      Application of ICISS Ps from a national pediatric benchmark population simplifies
      determination of expected mortality necessary to compute the expected component
      of National Surgical Quality Improvement Program. Analysis of these ratios of
      expected to observed mortality demonstrates variance among centers, defines
      performance against peers using the same benchmarks, and can drive performance
      improvement based on the objective evidence of injury diagnoses actually
      encountered.

PMID- 19590334
TI  - Commitment to COT verification improves patient outcomes and financial
      performance.
AB  - BACKGROUND: After an unsuccessful American College of Surgery Committee on Trauma
      visit, our level I trauma center initiated an improvement program that included
      (1) hiring new personnel (trauma director and surgeons, nurse coordinator,
      orthopedic trauma surgeon, and registry staff), (2) correcting deficiencies in
      trauma quality assurance and process improvement programs, and (3) development of
      an outreach program. Subsequently, our trauma center had two successful
      verifications. We examined the longitudinal effects of these efforts on volume,
      patient outcomes and finances. METHODS: The Trauma Registry was used to derive
      data for all trauma patients evaluated in the emergency department from 2001 to
      2007. Clinical data analyzed included number of admissions, interfacility
      transfers, injury severity scores (ISS), length of stay, and mortality for 2001
      to 2007. Financial performance was assessed for fiscal years 2001 to 2007. Data
      were divided into patients discharged from the emergency department and those
      admitted to the hospital. RESULTS: Admissions increased 30%, representing a 7.6%
      annual increase (p = 0.004), mostly due to a nearly fivefold increase in
      interfacility transfers. Severe trauma patients (ISS >24) increased 106% and
      mortality rate for ISS >24 decreased by 47% to almost half the average of the
      National Trauma Database. There was a 78% increase in revenue and a sustained
      increase in hospital profitability. CONCLUSION: A major hospital commitment to
      Committee on Trauma verification had several salient outcomes; increased
      admissions, interfacility transfers, and acuity. Despite more seriously injured
      patients, there has been a major, sustained reduction in mortality and a trend
      toward decreased intensive care unit length of stay. This resulted in a
      substantial increase in contribution to margin (CTM), net profit, and revenues.
      With a high level of commitment and favorable payer mix, trauma center
      verification improves outcomes for both patients and the hospital.

PMID- 19590335
TI  - Missed surgical intensive care unit billing: potential financial impact of 24/7
      faculty presence.
AB  - BACKGROUND: To efficiently capture evaluation and management (E&M) and procedural
      billing in our surgical intensive care unit (SICU), we have developed an
      electronic billing system that links to the electronic medical record (EMR). In
      this system, only notes electronically signed and coded by an attending generate
      billing charges. We hypothesized that capture of missed billing during nighttime
      and weekends might be sufficient to subsidize 24/7 in-house attending coverage.
      METHODS: A retrospective chart EMR review was performed of the EMRs for all SICU
      patients during a 2-month period. Note type, date, time, attending signature, and
      coding were analyzed. Notes without attending signature, diagnosis, or current
      procedural terminology (CPT) code were considered incomplete and identified as
      "missed billing." RESULTS: Four hundred and forty-three patients had 465
      admissions generating 2,896 notes. Overall, 76% of notes were signed and coded by
      an attending and billed. Incomplete (not billed) notes represented an overall
      missed billing opportunity of $159,138 for the 2-month time period (approximately
      $954,000 annually). Unbilled E&M encounters during weekdays totaled $54,758,
      whereas unbilled E&M and procedures from weeknights and weekends totaled $88,408
      ($44,566 and $43,842, respectively). Missed billing after-hours thus represents
      approximately $530K annually, extrapolating to approximately $220K in collections
      from our payer mix. Surprisingly, missed E&M and procedural billing during
      weekdays totaled $70,730 (approximately $425K billing, approximately $170K
      collections annually), and typically represented patients seen, but transferred
      from the SICU before attending documentation was completed. CONCLUSIONS: Capture
      of nighttime and weekend ICU collections alone may be insufficient to add faculty
      or incentivize in-house coverage, but could certainly complement other in-house
      derived revenues to such ends. In addition, missed daytime billing in busy modern
      ICUs can be substantial, and use of an EMR to identify missed billing
      opportunities can help create solutions to recover these revenues.

PMID- 19590336
TI  - Coagulopathy by hypothermia and acidosis: mechanisms of thrombin generation and
      fibrinogen availability.
AB  - BACKGROUND: Although the lethal triad of hypothermia, acidosis, and coagulopathy
      has been recognized for a decade, the underlying mechanisms related to the
      development of coagulopathy are not fully understood. Consequently, current
      strategy in treating trauma patients with coagulopathy is limited to "staying out
      of the trouble" instead of "getting out of trouble." A better understanding of
      the underlying mechanisms will facilitate the search for effective therapeutic
      approaches when this lethal triad cannot be avoided. METHODS: Reviewing recent
      studies that explored alterations of thrombin generation and fibrinogen
      availability caused by hypothermia and acidosis. RESULTS: Hypothermia and
      acidosis compromise thrombin-generation kinetics via different mechanisms.
      Hypothermia primarily inhibits the initiation phase, whereas acidosis severely
      inhibits the propagation phase of thrombin generation. Similarly, hypothermia and
      acidosis affect fibrinogen metabolism differently. Hypothermia inhibits
      fibrinogen synthesis, whereas acidosis accelerates fibrinogen degradation,
      leading to a potential deficit in fibrinogen availability. In addition,
      coagulation complications caused by acidosis cannot be immediately corrected by
      pH neutralization alone. CONCLUSIONS: Hypothermia and acidosis impair thrombin
      generation and fibrinogen availability via different mechanisms. Current data
      indicate that pH correction alone cannot immediately correct acidosis-induced
      coagulation impairments. Future studies are warranted to test the effects of pH
      neutralization in conjunction with fibrinogen supplementation in normalizing
      acidosis-induced clotting complications.

PMID- 19590337
TI  - Tympanic membrane perforation after combat blast exposure in Iraq: a poor
      biomarker of primary blast injury.
AB  - OBJECTIVE: The US military has reported over 10,000 improvised explosive device
      attacks attributing to over 400 deaths in Iraq in 2005. Otologic blast injury and
      tympanic membrane (TM) perforation have traditionally been used as a predictor,
      or biomarker, of serious or occult primary blast injury (PBI). Although combat
      injuries from the US-Iraq conflict have been described, the utility of TM
      perforation as a marker of PBI has not. The objective of this study is to
      determine the incidence of tympanic perforation in patients subject to blast
      exposures and describe its utility as a biomarker of more serious primary
      barotrauma, as observed at a US military hospital in Iraq. METHODS: In our
      institutional review board-approved study, all patients during a 30-day period
      who arrived at a tertiary US military hospital in Iraq were evaluated. All
      patients with blast injures were identified on arrival to the hospital emergency
      department and were followed up through their hospital course and evacuation to
      the United States to assure they received proper otolaryngology evaluation and
      follow-up. Demographic data and manifestations of PBI (TM perforation,
      pneumothorax, pulmonary contusion, nonpenetrating facial sinus injury, and bowel
      perforation) and other combat injuries were recorded. The diagnostic tests and
      clinical examination findings used to identify these complications were also
      recorded. RESULTS: One hundred sixty-seven patients were enrolled over 30 days.
      All blast exposures resulted from primary or secondary explosions from munitions
      used in combat. This included both combatants and civilians. All patients were
      men. The mean patient age was 28 years (range, 12-55 years). Sixteen percent (27
      of 167) of blast-exposed patients had TM perforation. Thirteen of 27 patients
      with perforations had bilateral perforations. Twelve of 167 patients (7%) had
      PBI. Six of 12 patients (50%) with PBI had TM perforation. The use of TM
      perforation as a biomarker for PBI resulted in a sensitivity of 50% (95% CI, 22
      78%) and specificity of 87% (95% CI, 81-92%). CONCLUSIONS: Both TM perforation
      and PBI are rare with improvised explosive devices and other explosive devices in
      the current Iraqi-US conflict. Contrary to previous belief and management
      guidelines, TM perforation had low sensitivity for serious or occult PBI and was
      not a good biomarker. On the basis of the findings of this study, the absence of
      TM perforation does not appear to exclude other serious PBI.

PMID- 19590338
TI  - Spontaneous fractures of Judet struts.

PMID- 19590339
TI  - Traumatic intramyocardial dissection with mitral regurgitation.

PMID- 19590341
TI  - Seriously questioning a long established principle of resuscitation.

PMID- 19590342
TI  - Fixation of the fracture clavicle for early restoration of the patient to
      preinjury status.

PMID- 19590343
TI  - Evaluating compliance to the Scandinavian guidelines on mild head injury.

PMID- 19590345
TI  - Introduction 2008 Forging New Frontiers: Securing Your Organization's Future--the
      13th Annual Conference of the Injury Free Coalition for Kids.

PMID- 19590346
TI  - Fall-related pediatric brain injuries: the role of race, age, and sex.
AB  - BACKGROUND: Falls remain a major cause of childhood morbidity and mortality. To
      improve effectiveness of our prevention program, we used our electronic injury
      surveillance database to analyze patient variables and the incidence of fall
      related brain injury. METHODS: The database was queried for all injuries treated
      in the pediatric emergency department for which the word "fall" was listed as
      part of the chief complaint. Age, sex, and mechanism variables were cross
      tabulated for analysis with traumatic brain injury (TBI) codes. RESULTS: Between
      June 2005 and June 2008, the electronic surveillance system reported 39,718
      injury-related visits to the pediatric emergency department. Falls were reported
      in 3,436 patients (2,107 males, 1,329 females). TBI occurred from falls in 171
      patients. Although black children had a higher fall rate (69.24%) than white
      children (23.75%) and non-black, non-white children (7.01%), white children had
      the highest TBI rate from falls (9.47%). TBI from falls occurred at a lower mean
      age for females (5.40 +/- 4.45) than males (6.6 +/- 5.15) and for non-whites
      (5.98 +/- 4.88) than whites (6.21 +/- 4.93). Multiple logistic regression
      demonstrated a significant influence of age, race, and sex on the likelihood that
      a fall results in TBI. Females have a higher risk of TBI from falls than males
      from ages 0 to 11.5. This runs contrary to previous studies suggesting that
      toddler males are at highest risk for TBI. CONCLUSION: A disproportionate number
      of infants, toddlers, and adolescents sustain brain injury from falls. Race and
      sex group differences mandate enhanced focus on environmental safety and risk
      taking behaviors.

PMID- 19590347
TI  - The impact of community-built playgrounds on the community.
AB  - BACKGROUND: Community-built playgrounds have been an integral component of Injury
      Free Coalition for Kids sites as they work with communities to provide safe
      places for children to play. The purpose of this pilot survey was to explore the
      potential impact of the community-built playground on the community. METHODS: A
      survey was developed and sent electronically via an Injury Free listserve to the
      Injury Free sites that had built one of the 29 Injury Free playgrounds between
      2002 and 2007. Variables examined included condition and maintenance of the
      playground, vandalism, and community participation. Open-ended questions were
      used to examine the impact of the playground on the community and school.
      Descriptive statistics were used to describe quantitative data. Open-ended
      responses were collated and grouped into themes. RESULTS: Surveys were returned
      from 28 Allstate playground sites. The playgrounds were built within the last 6
      years with the majority (64%) built 3 or more years ago. Although 17 of the
      playgrounds sustained minor vandalism, 11 of the sites reported the vandalism was
      corrected by the community. Community impact themes centered on revitalization
      and empowerment, safety, and social capital changes whereas school impact themes
      centered on socialization and health. CONCLUSIONS: From the perspective of the
      program coordinators, the playgrounds had a positive impact on the communities.
      Further research within this arena is needed to explore the relationship of
      community-built playgrounds and community development.

PMID- 19590348
TI  - Errare humanum est--Seneca the Younger.

PMID- 19590349
TI  - Motor vehicle occupant injury and related hospital expenditures in children aged
      3 years to 8 years covered versus uncovered by booster seat legislation.
AB  - BACKGROUND: Although most states have infant restraint laws, booster seat
      legislation for older children has not been implemented universally despite
      evidence of effectiveness. We examined injury and expenditures for motor vehicle
      traffic (MV) occupant injury among 3 year to 8 year olds covered versus uncovered
      by booster seat legislation. METHODS: Age, state of residence/hospitalization,
      and month of injury were used to examine injury, deaths, and expenditures due to
      MV occupant injury in children covered versus uncovered by booster seat
      legislation. Data sources included Kids Inpatient Database 2003 and Web-based
      Injury Statistics Query and Reporting System. Statistical analyses used chi,
      Fisher's exact, and analysis of variance. Odds ratios were calculated with 95%
      confidence intervals (CI). RESULTS: Children covered by booster seat legislation
      were less likely to be hospitalized for MV occupant injury than uncovered
      children (odds ratio, 0.78; 95% CI, 0.69-0.88). MV occupant injury constituted a
      smaller proportion of total injury expenditures in children covered (4.9%) versus
      uncovered (6.9%) by booster seat legislation. Covered children residing in areas
      with zip code incomes above the median had 26% lower MV occupant/total injury (p
      = 0.001) compared with 13% lower MV occupant/total injury for those below the
      median income (p = 0.0712). The proportion of injury dollars spent for MV
      occupant injury was higher in self-pay children for covered (7.8%) and uncovered
      (8.9%) children. CONCLUSIONS: This study suggests that booster seat laws are
      associated with a lower proportion of injury expenditures for MV occupant
      injuries in booster seat-aged children. Observed income disparities raise
      questions regarding whether access to booster seats, quality of affordable seats,
      and proper use and/or enforcement strategies impede legislative effectiveness.

PMID- 19590351
TI  - Evaluating the educational component of a hospital-based child passenger safety
      program.
AB  - BACKGROUND: Interventions that combine educational programs and discounted child
      safety seats have been demonstrated to improve parental child passenger safety
      knowledge and practices. An educational component consisting of an hour-long
      bilingual (English/Spanish) class for parents was added to a hospital-based
      safety seat program. Researchers sought to evaluate participant knowledge
      retention and safety practices after the class and to identify parental
      motivators and barriers for correct safety seat use. In particular, researchers
      were interested in evaluating a child passenger safety program that includes both
      individualized and group-based educational components in addition to a giveaway
      seat program, and also serves a subset of Latinos, mostly from the Dominican
      Republic and the Guatemala, that is less frequently studied. METHODS: A 15-minute
      telephone survey was conducted in English or Spanish with past participants (n =
      79) of the program. Descriptive statistics and odds ratios were generated to
      determine statistical significance. Qualitative data from open-ended questions
      were coded and grouped categorically. RESULTS: The final sample (n = 79) was
      mostly women (93.7%), Hispanic (78.5%), and foreign-born (77.2%). Six months
      after participating in the program, there was a statistically significant
      decrease in parental knowledge regarding appropriate safety seat transitions to
      booster seats and correct knowledge of the state child safety seat law-with odds
      ratios of 0.35 (95% CI: 0.13-0.93) and 0.16 (0.04-0.54), respectively. Most
      commonly reported motivators were safety and fear of police enforcement. Most
      commonly reported barriers to safety seat use were parents not understanding the
      importance of safety seats and being in a rush. CONCLUSIONS: Parents surveyed >
      or =6 months after receiving the child passenger safety program displayed less
      correct safety seat knowledge compared with parents surveyed <6 months after
      participating in the program. Parents noted multiple barriers to safety seat use.
      Programmatic changes that merit future study include (1) sending reminders to
      parents to refresh safety seat transition knowledge, particularly for older
      children, and (2) incorporating curriculum components that address the parental
      motivators and barriers to correct safety seat use in the class.

PMID- 19590350
TI  - Race and ethnic differences in a multicenter study of home safety with vouchers
      redeemable for free safety devices.
AB  - BACKGROUND: Most injuries to infants occur at home and are known to have a
      modifiable component. Additional information on safety behaviors, practices, and
      device ownership could inform prevention programs aimed at reducing injury
      related race and ethnic disparities. METHODS: This study is a secondary data
      analysis of race and ethnic differences in home safety using data collected by
      the Connecticut, Ohio, Pennsylvania, Minnesota, and New York sites of the Injury
      Free Coalition for Kids. Study participants were English- and Spanish-speaking
      parents/guardians of infants aged 4 months to 6 months. All participants received
      a voucher redeemable for free safety devices and educational materials. RESULTS:
      Five hundred forty-two study participants were 37.8% black, 41.7% Hispanic, 10.5%
      white, and 10.0% other race. Whites more frequently owned/had safety devices
      including cabinet latches (chi2 =28.9, p < 0.0001), drawer latches (chi2 =21.4, p
      < 0.0001), bath thermometers (chi2 =22.5, p < 0.0001), electric outlet covers
      (chi2 =15.9, p = 0.0004), and poison control number (chi 2=93.8, p < 0.0001).
      Practice of unsafe behaviors, such as stomach sleep position, was higher in
      blacks (29.3%) than whites (15.8%) or Hispanics (17.7%) (chi2 =11.8, p < 0.0083).
      Overall, 62.1% redeemed vouchers, but this varied significantly by ethnicity:
      blacks (42.2%), non-Hispanic whites (64.6%), and Hispanics (76.3%) (chi2 = 48.5,
      p < 0.0001). CONCLUSIONS: Compared with whites, both blacks and Hispanics were
      less likely to own a variety of safety devices at baseline, but Hispanics were
      more likely than blacks to redeem vouchers. This one shot voucher program was
      effective at increasing device ownership, but was not sufficient alone to achieve
      population saturation of safety devices.

PMID- 19590352
TI  - Is the "seat belt sign" associated with serious abdominal injuries in pediatric
      trauma?
AB  - BACKGROUND: The "seat belt sign" (SBS) has been reported to be highly associated
      with intra-abdominal injury. This study defines its predictive value in
      identifying injuries in a large pediatric trauma population. METHODS: At a level
      I pediatric trauma center, we performed a retrospective review of trauma flow
      sheets for all motor vehicle crash victims (ages, 0-20) requiring trauma team
      activation during 2005 and 2006. All patients with an abdominal SBS recorded were
      included in the analysis. RESULTS: Of 331 patients (mean age, 9.96 years), an SBS
      was present in 54 (16%) of these children. Abdominal injury was identified by
      computed tomography scan or intraoperatively in 12 (22%) of these children. Three
      (6%) children with SBS required operative intervention. Two had a bowel injuries
      and one had a negative laparoscopy. SBS and abdominal tenderness were reported in
      30 (56%) patients; 8 (15%) of whom sustained abdominal injury. Of the 277 (84%)
      children without SBS, 36 (13%) had abdominal injuries. Four (11%) of these had a
      positive laparotomy with three having a bowel injuries. The relative risk of an
      abdominal injury given an SBS was 1.7 (CI 0.96-2.69; p = 0.078). Four (1.4%)
      children without SBS died of head injuries compared with zero with SBS. The SBS
      had a sensitivity of 25% and a specificity of 85%. CONCLUSIONS: The SBS was not
      significantly associated with abdominal injury in our population. Patients
      without SBS had a higher Injury Severity Score and accounted for all of the
      deaths. SBS may not be as predictive of abdominal injury as previously reported.

PMID- 19590353
TI  - Screening for risky alcohol use among caregivers of pediatric trauma patients: a
      pilot study.
AB  - BACKGROUND: Injury is the leading cause of death for children and has been linked
      to caregiver drinking. Screening and brief intervention for risky drinking has
      been successful in adult trauma centers but has not been evaluated in caregivers
      of pediatric trauma patients. The purpose of this study was to investigate a
      pilot screening process for risky drinking caregivers, to determine rates of
      risky alcohol use, and to assess potential relationships between risky drinking
      and child safety behaviors. METHODS: Caregivers of pediatric trauma patients were
      screened by trained injury prevention educators. The screening assessed risky
      drinking, tobacco and illicit drug use, and child safety behaviors. Data were
      analyzed using descriptive analysis, frequency comparisons, and univariate
      logistic regression. RESULTS: Over 7 months, 295 caregivers were screened; 32.5%
      (n = 96) screened positive for risky alcohol use. For 173 injured children, one
      caregiver was screened, and for 61 children, two caregivers were screened. In the
      one-caregiver group, 29% (n = 50) screened positive for risky drinking. For the
      two-caregiver group, in 18% (n = 11) of the cases, both caregivers screened
      positive, whereas in 39% (n = 24) only one caregiver screened positive. Males
      were more likely to screen positive (p < 0.01). Relationships between reported
      child safety behaviors and risky drinking were of interest, but not statistically
      significant. CONCLUSIONS: The results of our study demonstrate that a substantial
      number of caregivers of pediatric trauma patients will self-report risky drinking
      behaviors, and therefore, an opportunity exists for these families to receive the
      benefits of screening and brief intervention programs in pediatric trauma care
      settings.

PMID- 19590354
TI  - Motor vehicle injury, mortality, and hospital charges by strength of graduated
      driver licensing laws in 36 States.
AB  - BACKGROUND: To assess the relation between strength of graduated driver licensing
      (GDL) laws and motor vehicle (MV) injury burden, this study examined injury
      mortality, hospitalizations and related charges for 15 year to 17 year olds in 36
      states by strength of GDL legislation. METHODS: Data sources include the CDC's
      Web-Based Injury Statistics Query and Reporting System (WISQARS) and the 2003
      Healthcare Cost and Utilization Kids' Inpatient database (KID). Hospital
      admissions for injuries in 15 year to 17 year olds (n = 49,520) are unweighted.
      Injury severity was assessed using ICDMAP-90 and International Classification of
      Injury Severity Scores. The Insurance Institute for Highway Safety rating system
      was used to categorize legislative strength: good, fair, marginal/poor, and none.
      Logistic regression was used to assess independent predictors of MV injury.
      RESULTS: MV injury accounted for 14.6% of all-cause injury-related hospital
      admissions with 47.7% classified as drivers. Total MV occupant mortality was
      14.6% lower after enactment of GDL with greater improvement observed in the good
      law category (26.0%). In multivariate models for hospitalized injury, all GDL law
      categories were protective for MV driver injury in 16 year olds. Compared with
      whites, black and Hispanic teens were more frequently injured as passengers than
      drivers. The contribution of MV occupant to all-cause injury-related hospital
      charges was 16.0% lower in good versus no-GDL categories and 39.5% lower for MV
      drivers. CONCLUSIONS: These findings suggest that the presence of any GDL
      legislation is associated with a lower burden of MV-related injury and
      expenditures with the largest differences observed for 16-year-old drivers.

PMID- 19590355
TI  - Intervention improves physician counseling on teen driving safety.
AB  - BACKGROUND: As part of a statewide campaign, we surveyed physician attitudes and
      practice regarding teen driving safety before and after a brief intervention
      designed to facilitate in office counseling. METHODS: A 31-item self-administered
      survey was mailed to Connecticut physicians, and this was followed by a mailing
      of teen driving safety materials to physician practices in the state. A
      postintervention survey was mailed 8 months after the presurvey. RESULTS: A total
      of 102 physicians completed both the pre and postsurveys. Thirty-nine percent
      (39%) reported having had a teen in their practice die in a motor vehicle crash
      in the presurvey, compared with 49% in the postsurvey. Physician counseling
      increased significantly for a number of issues: driving while impaired from 86%
      to 94%; restrictions on teen driving from 53% to 64%; teen driving laws from 53%
      to 63%; safe vehicle from 32% to 42%; parents model safe driving from 29% to 44%;
      and teen-parent written contract from 15% to 37%. CONCLUSIONS: At baseline, the
      majority of physicians who provide care to teenagers in Connecticut report
      discussing and counseling teens on first wave teen driver safety issues (seat
      belts, alcohol use), but most do not discuss graduate driver licensing laws or
      related issues. After a brief intervention, there was a significant increase in
      physician counseling of teens on teen driving laws and on the use of teen-parent
      contracts. Additional interventions targeting physician practices can improve
      physician counseling to teens and their parents on issues of teen driving safety.

PMID- 19590357
TI  - Lessons from a statewide pilot of "the battle of the belts project" in a state
      without a primary seat belt law.
AB  - BACKGROUND: Teen driving issues result in higher rates of injury. The Arizona
      Department of Health Services recommended addressing teen seat belt use. Driver
      belt use has been reported as lowest among those transporting passengers of
      similar age. Self-management is essential for long-term behavioral change. Peer
      to-peer approaches have been shown to be effective. A group of trauma center
      representatives in Arizona replicated the Battle of the Belt program that began
      in 2005 in Missouri to address teen seat belt use using a peer-to-peer approach.
      METHODS: Each trauma center "adopted" one school securing an adult champion and a
      group of students responsible for the project. Monetary awards were made for the
      schools with the most improved and highest seat belt use. A toolkit was provided.
      Random observations measured change. Injury Free of Phoenix provided data entry
      and analysis. RESULTS: Of the six original schools, one withdrew because of the
      death of a student in a motor vehicle crash. A total of 2,892 vehicles were
      observed. Significant increases were found for drivers (70.6-91.4%, p = 0.000),
      front passengers (51.1-67.9%, p = 0.000), and first rear passenger (26.2-68.8%, p
      = 0.002). Additional rear passenger use also increased, but small numbers created
      unstable results. The largest changes were seen in schools with closer trauma rep
      involvement. Odds ratios were computed for the likelihood of belted passengers
      based on driver seat belt use (baseline 9.08, follow-up 5.5). CONCLUSIONS: The
      peer-to-peer methods appear to be productive with long-term impact unknown.
      Results associated with drivers compared with passengers may indicate youth
      "thinking for themselves."

PMID- 19590356
TI  - Teenagers--we thought we knew--we didn't--lessons learned.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of death and disability
      to teenagers in the United States. The development of resources to assist
      physicians and high school teachers in anticipatory guidance of adolescent
      drivers and their parents provides a way to disseminate important information. As
      adults with years of experience working with teens in a variety of settings, we
      hypothesized we would have similar responses to a standardized message as
      teenagers themselves. METHODS: Convenience-based focus groups of teens and adults
      evaluated the resource materials and their responses were collected. The adult
      group was made up of trauma, injury prevention and school staff, the teen group
      was made of students in random familiar settings (school programs, sports events,
      and mall). Each group was asked to evaluate three posters and select the one most
      likely to attract the attention of a teen and be most effective at supporting
      positive driving behavior. Seat belt usage was the primary message of all three
      posters. RESULTS: Teens and adults have dramatically different responses to the
      posters. The primary choice of the adults was never selected by the teens and the
      primary choice of the adolescents was never the choice of the adults.
      Interestingly, both groups agreed that one of the posters was ineffective.
      CONCLUSION: Experience with adolescents does not necessarily result in successful
      prediction of teen choices. The focus group experience gives the teen a voice in
      the process and ensures the message being sent is the one being received.
      Involving teens in development of educational materials targeted at this
      population is critical for successful implementation.

PMID- 19590358
TI  - The effectiveness of a peer lead smart driving campaign on high school students'
      driving habits.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of death among teenagers.
      In 2007, 48 youth between the ages of 15 years and 19 years died in traffic
      crashes and almost 4,780 were injured in Minnesota. Of those killed, only 42.8%
      of teens were wearing their seat belt. The Drive Smart Challenge is a 4-week peer
      lead safety campaign with the goal to increase safe driving habits for high
      school age students. METHODS: The 4-week challenge begins with a seat belt check
      of teen drivers and their front seat passengers at the school's parking lot. Each
      school's student-leadership group then selected and implemented at least eight
      Smart Driving interventions from a manual they are provided. A post seat belt
      check is conducted at the conclusion of the challenge. RESULTS: In 2008, 11
      schools agreed to participate in the challenge. More than 21,000 students were
      exposed to the safe driving messages through public address announcements,
      posters, mock car crashes, mothers against drunk driving car demonstrations,
      parent contracts, guest speakers, student developed videos, and web sites. In the
      end, all the schools documented an increase in seat belt use. The most improved
      school documented a 15% increase. CONCLUSION: The Drive Smart Challenge is an
      effective way to get teens involved in a safe driving campaign. Further studies
      should be done to determine how often teen drivers and their passengers need to
      be exposed to the messages of the Drive Smart Challenge in order for optimal
      effectiveness in behavior and attitude change.

PMID- 19590376
TI  - Facial pain.
AB  - Facial pain is a debilitating disorder if left untreated. Too often, patients are
      labeled as having psychopathology when face pain etiology is unclear. These
      patients are categorized as "atypical," "idiopathic," or "psychogenic." Cases of
      facial pain involving neuropathic, neurovascular, musculoskeletal, as well as
      intracranial and extracranial systems will be reviewed. Peripheral and central
      mechanisms associated with these disorders are used to provide an update of these
      frequently seen clinical issues.

PMID- 19590377
TI  - Decompressive hemicraniectomy for malignant middle cerebral artery infarction: an
      update.
AB  - BACKGROUND: Malignant middle cerebral artery (MCA) infarction is a devastating
      disease affecting a minority of stroke victims. The mortality rate from malignant
      MCA infarction managed with conservative medical treatment is estimated at 80%.
      Standard medical management includes physiologic support, osmotherapy, intubation
      and mechanical ventilation, and intracranial pressure monitoring. Decompressive
      hemicraniectomy has been viewed with skepticism because of lack of evidence from
      randomized controlled trials. METHODS: Narrative review of recent surgical
      evidence in favor of hemicraniectomy. RESULTS: Current evidence from randomized
      controlled trials and a recent pooled analysis, show clear benefit from
      hemicraniectomy with improved survival and better functional outcomes.
      DISCUSSION: Hemicraniectomy for malignant MCA infarction is a life saving
      procedure. Further data on quality of life outcomes and patient and caregiver
      burden are required. Until that time, selection of patients for hemicraniectomy
      still requires an individual approach.

PMID- 19590378
TI  - Rehabilitation approaches to hemineglect.
AB  - BACKGROUND: Hemineglect is a difficult neurologic condition to rehabilitate. It
      arises predominantly from right brain injury, and manifests heterogeneously in
      clinical deficits such as poor visual exploration to the left, inaccurate
      assessment of the midpoint of a line, left limb hypokinesis, and anosognosia.
      Most of the cognitive dysfunction produced by hemineglect is because of an
      asymmetric distribution of attention, either with respect to extrapersonal space
      or to an object being viewed. Many treatments draw on hemineglect theory to
      attempt to mediate the basic asymmetry of attention. REVIEW SUMMARY: Treatment
      approaches can be divided into 2 main categories. Extrinsic or "top-down"
      approaches require active participation of the patient under the guidance of a
      therapist. The most common approach of this type is visual scanning therapy in
      which the patient is continually instructed to move the gaze leftward into the
      neglected space. Intrinsic or "bottom-up" approaches manipulate stimulus
      characteristics, sensory input, or the brain directly in an attempt to alter the
      interhemispheral attentional imbalance. Examples of this approach include
      vestibular stimulation of the left side, sensory activation of the left limb, and
      transcranial magnetic stimulation of the overactive left hemisphere. Combined
      approaches such as prism adaptation have also shown good results. CONCLUSIONS:
      Hemineglect is a complicated disorder that poses challenges to treatment. A
      paucity of clinical trial evidence limits our ability to extrapolate experimental
      mediation of hemineglect to globally improved functioning. Nonetheless, many
      treatment approaches appear promising. Underlying neuroscience may help guide
      future treatment approaches.

PMID- 19590379
TI  - Management of acute intracranial hypertension: a review.
AB  - BACKGROUND: Patients with acute brain injury from various etiologies commonly
      develop increased intracranial pressure. Acute intracranial hypertension
      resulting from elevation of intracranial pressure is a medical emergency
      requiring prompt diagnosis and management. Appropriate and timely management
      strategies result in better patient outcome in an otherwise severely debilitating
      or fatal disease process. REVIEW SUMMARY: The clinical manifestation and
      principles of management of acute intracranial hypertension are discussed and
      reviewed. Acute treatment protocols are presented in an algorithm-based format
      aimed at utilizing the current available management strategies and suggested
      therapeutic goals. Individualization of specific therapeutic modalities is
      emphasized to optimize the clinical outcome. CONCLUSIONS: Clinicians treating
      patients with acute brain injury should be familiar with the principles of
      management of increased intracranial pressure. Since acute intracranial
      hypertension is a potentially reversible condition, high index of suspicion, and
      low threshold for diagnostic and therapeutic strategies will improve patient
      care.

PMID- 19590380
TI  - Bilateral temporal glioma presenting as a paraneoplastic limbic encephalitis with
      pure cognitive impairment.
AB  - INTRODUCTION: Memory impairment caused by bilateral hippocampal primitive brain
      tumor is rarely reported. Clinical and MRI features can mimic paraneoplastic
      limbic encephalitis (PLE), and the differential diagnosis between these 2
      entities may be difficult. CASE REPORT: We report the case of a 42-year-old woman
      presenting with amnesia without neurologic focal signs at clinical examination.
      The neuroimaging features consisted of bilateral limbic hyperintensities on T2
      weighted and FLAIR brain MRI. Despite exhaustive biologic and radiologic
      investigations, no specific etiology was found. The diagnosis of paraneoplastic
      limbic encephalitis was suspected, although antineuronal antibodies were negative
      and no cancer was detected after the first evaluation. Eight months after onset,
      the memory complaint of the patient increased along with disability in activities
      of the daily living, the neurologic examination slightly changed with frontal
      neurologic signs and the brain MRI showed a new cystic lesion in the left
      hippocampus with enhancement after contrast administration. The left temporal
      tumor was resected and the neuropathological examination was consistent with
      gliomatosis cerebri with a focal high grade astrocytoma. CONCLUSIONS: This case
      highlights the need to consider the possibility of infiltrative gliomatosis in
      patients presenting with features of paraneoplastic limbic encephalitis.

PMID- 19590381
TI  - Headaches in the different phases of relapsing-remitting multiple sclerosis: a
      tendency for stabbing headaches during relapses.
AB  - INTRODUCTION: Primary headaches are known to be associated with multiple
      sclerosis. We aimed to determine headaches using ICHD-II in different phases of
      relapsing-remitting multiple sclerosis, and the correlation between headaches and
      several features of the disease. RESULTS: Migraine (41.2%) and tension-type
      headaches (20.6%) were the most common headaches in remission, and primary
      stabbing headache (PSH) (27.8%) was common in the relapsing phase. Although
      headaches seemed to occur independently of disease duration, extended disability
      status scale, beck depression inventory scores, and treatments, the total number
      of headaches was correlated with periventricular lesions (P = 0.03) and tension
      type headaches were correlated with spinal lesions in remission (P = 0.02). Total
      number of headaches was correlated with brain stem lesions in the relapsing phase
      (P = 0.05). CONCLUSION: The high frequency of PSHs in relapse was notable, and,
      to the best of our knowledge, PSH was not reported in relapsing-remitting
      multiple sclerosis before. Further studies with larger samples are recommended.

PMID- 19590382
TI  - Digital neuropathy of the median and ulnar nerves caused by Dupuytren's
      contracture: Case report.
AB  - INTRODUCTION: Digital neuropathy is a pure sensory neuropathy of a digital nerve.
      It may be caused by acute or chronic local trauma or pressure, or accompany
      systemic illnesses such as rheumatoid disease, leprosy, Raynaud disease,
      dysproteinemia, or diabetes mellitus. We describe an extraordinary case of
      digital neuropathy of the median and ulnar nerves caused by Dupuytren
      contracture. CASE REPORT: A 56-year-old right-handed man was presented with
      numbness and tingling of the little finger of the right and ring finger of the
      left hand. The clinical and EMG findings in this patient were consistent with a
      lesion of the median and ulnar palmar digital nerves of the right and left ring
      and little fingers. CONCLUSION: Dupuytren tissue usually affects the palmar
      fascia, superficial to the digital nerves, and it may rarely affect the spiral
      cord in the digits. A spiral cord may cause sensory loss due to impingement of
      digital nerves or Dupuytren tissue may have been compressing the palmar digital
      nerves against the relatively inelastic deep transverse metacarpal ligament. As a
      result, digital neuropathy can develop in those with Dupuytren's contracture, and
      nerve conduction studies should also be performed to determine the condition. New
      studies are needed to provide better diagnostic criteria for the condition.

PMID- 19590383
TI  - Juvenile muscular atrophy of the distal upper extremity (hirayama disease) in two
      lanky look-alike brothers.
AB  - BACKGROUND: Juvenile muscular atrophy of the distal upper extremity (Hirayama
      disease) is a sporadic disorder, but very rarely occurs in a familial pattern.
      OBJECTIVE: To describe the clinical features of Hirayama disease in 2 brothers,
      especially the look-alike anatomic physiques and magnetic resonance imaging (MRI)
      findings. DESIGN: Case report. PATIENTS: Two physically look-alike young brothers
      with Hirayama disease. RESULTS: Clinical symptoms of the present brothers were
      consistent with those of sporadic cases. Their lanky physique, clinical features,
      and MRI findings looked alike to each other. CONCLUSIONS: The pathogenesis of
      familial Hirayama disease is not well understood. The present brothers looked
      alike in terms of their physical frame and clinical symptoms. These findings
      suggest that similar mechanical damage against the cervical spinal cord by look
      alike anatomic frame of the neck could be an important factor of familial
      Hirayama disease in the present brothers.

PMID- 19590385
TI  - Stiff person syndrome: presentation of a case with repetitive complex discharges
      in electromiograms.
AB  - INTRODUCTION: Stiff person syndrome is characterized by rigidity of axial and
      proximal limb muscles, associated with muscle spasms, triggered by unexpected
      acoustic or somesthetic stimuli. It usually has an autoimmune basis, in which the
      blood contains antiglutamate decarboxylase antibodies, and is associated with
      different types of autoimmune diseases. The electromyogram provides evidences of
      continuous muscular activity. CASE REPORT: A 41-year-old woman with a history of
      diabetes mellitus type I, Hashimoto thyroiditis, vitiligo, and pernicious anemia
      developed symptoms compatible with stiff person syndrome. In the electromyogram,
      in addition to continuous muscular activity, there was evidence of complex
      repetitive activity in the form of doublets and triplets. CONCLUSIONS: Given the
      absence of clinical or electrophysiological neuropathic affectation, the presence
      of doublets and triplets in our patient could be due to a subclinical functional
      alteration of alpha motoneurons. They could produce the complex repetitive
      discharges when released from the inhibition mediated by GABAergic neurons.

PMID- 19590384
TI  - MRI deterioration in herpes simplex encephalitis despite clinical recovery.
AB  - OBJECTIVES: Herpes simplex virus type 1 is a sporadic cause of viral
      encephalitis. Relapse of encephalitis occurs in up to 10% of patients, manifested
      by recurrent symptoms, clinical and MRI findings, and the presence of herpes
      simplex virus type 1 DNA in the cerebrospinal fluid (CSF). METHODS: We describe
      the clinical features, MRI findings and outcome in 2 patients with herpes simplex
      encephalitis during the acute phase and 6 months after the onset of encephalitis.
      RESULTS: Both patients had a good response to treatment and an excellent
      recovery. Despite clinical recovery, in a 6-month follow-up MRI lesions
      consistent with recurrence were disclosed, without any clinical findings or CSF
      abnormalities. CONCLUSIONS: The mechanism underlying this MRI deterioration is
      unclear and an immune-mediated mechanism may be involved. Thus, MRI deterioration
      after herpes simplex encephalitis should be interpreted with caution and it does
      not always represent a relapse, especially when the imaging studies do not
      correlate with the clinical and CSF findings.

PMID- 19590386
TI  - 10 most commonly asked questions about training in interventional neurology.

PMID- 19590387
TI  - Efficacy of rivastigmine for cognitive symptoms in Parkinson disease with
      dementia.
AB  - BACKGROUND: Impairment of multiple neurotransmitter networks, including
      acetylcholine, may contribute to the cognitive impairment in patients with
      Parkinson disease with dementia (PDD). Therefore, cholinesterase inhibitors might
      improve cognitive function in PDD. On the other hand, enhancing cholinergic
      function could plausibly worsen features of parkinsonism. OBJECTIVE: To determine
      if oral cholinesterase inhibitors improve measures of cognitive outcome and are
      tolerated by people with PDD. METHODS: We addressed the question through the
      development of a critically appraised topic. Participants included consultant and
      resident neurologists, clinical epidemiologists, a medical librarian, and
      behavioral neurology and movement disorder specialists. Participants began with a
      structured clinical question, devised search strategies, compiled the best
      evidence, performed a critical appraisal, summarized the evidence, provided
      commentary, and declared bottom-line conclusions. RESULTS: A randomized
      controlled trial (n = 541) showed that, compared with placebo, rivastigmine
      (mean, 8.6 mg/d) significantly improved scores on 2 coprimary cognitive outcome
      scales in PDD, including the Alzheimer disease Cooperative Study-Clinician's
      Global Impression of Change. When dichotomized to evaluate clinically significant
      benefit (moderate or marked improvement), this outcome was not significant (risk
      difference = 5.3%; 95% confidence interval (CI) = -1.6 to 12.1). The number
      needed to treat (NNT) to avoid clinically significant worsening of cognition was
      10 (95% CI = 6-28). The NNT for the combined outcome of either achieving
      clinically significant benefit or avoiding significant worsening was 7. The
      numbers needed to harm for cholinergic side effects were 9 (95% CI = 5-24) for
      parkinsonian symptoms and 11 (95% CI = 6-32) for rivastigmine discontinuation due
      to any side effect. CONCLUSION: Rivastigmine therapy for PDD is associated with
      significant tradeoffs in efficacy and adverse effects. Carefully monitored trials
      of rivastigmine may provide meaningful benefits for a minority of PDD patients.

PMID- 19590388
TI  - The autonomic nervous system: part two.

PMID- 19590389
TI  - Gangliosides determine the amyloid pathology of Alzheimer's disease.
AB  - Gangliosides, GM3 and GM1, are suggested to accelerate the deposition of the
      amyloid beta-protein as amyloid angiopathy and senile plaques, respectively, in
      the Alzheimer brain. We investigated the profile of amyloid deposition in the
      brains of transgenic mice expressing a mutant amyloid precursor protein with a
      disrupted GM2 synthase gene, in which GM3 accumulates whereas GM1 is lacking.
      These mice showed a significantly increased level of deposited amyloid beta
      protein in the vascular tissues. Furthermore, formation of severe dyshoric-form
      amyloid angiopathy, in which amyloid extended from the blood vessel walls deeply
      into the surrounding parenchyma was observed. Our results indicate that the
      expression of gangliosides is a critical determinant for the amyloid pathology in
      the Alzheimer brain.

PMID- 19590390
TI  - Electrophysiological correlates of reduced pain perception after theta-burst
      stimulation.
AB  - In an earlier study, we reported the antinociceptive effects of a special
      repetitive transcranial magnetic stimulation paradigm: continuous theta-burst
      stimulation (cTBS), when applied to human motor cortex. Here, we investigated
      whether the reduced subjective pain perception of 10 healthy individuals could be
      measured by changes in laser-evoked potentials, a reflection of pain related
      activations in the operculoinsular and midcingulate cortex. To minimize the
      effect of habituation during repeated laser stimulation, a bioadaptive design was
      used. However, both pain ratings and laser-evoked potential amplitudes were
      reduced after real and sham cTBS. When compared with sham stimulation, cTBS
      resulted in a significantly greater diminution of pain ratings and N2-P2
      amplitudes on the hand contralateral to the site of motor cortex stimulation.

PMID- 19590391
TI  - Swearing as a response to pain.
AB  - Although a common pain response, whether swearing alters individuals' experience
      of pain has not been investigated. This study investigated whether swearing
      affects cold-pressor pain tolerance (the ability to withstand immersing the hand
      in icy water), pain perception and heart rate. In a repeated measures design,
      pain outcomes were assessed in participants asked to repeat a swear word versus a
      neutral word. In addition, sex differences and the roles of pain catastrophising,
      fear of pain and trait anxiety were explored. Swearing increased pain tolerance,
      increased heart rate and decreased perceived pain compared with not swearing.
      However, swearing did not increase pain tolerance in males with a tendency to
      catastrophise. The observed pain-lessening (hypoalgesic) effect may occur because
      swearing induces a fight-or-flight response and nullifies the link between fear
      of pain and pain perception.

PMID- 19590392
TI  - The frontopolar cortex mediates event knowledge complexity: a parametric
      functional MRI study.
AB  - Event knowledge is organized on the basis of goals that enable the selection of
      specific event sequences to organize everyday life activities. Although the
      medial prefrontal cortex represents event knowledge, little is known about its
      role in mediating event knowledge complexity. We used functional MRI to
      investigate the patterns of brain activation while healthy volunteers were
      engaged in the task of evaluating the complexity (i.e. numbers of events) of
      daily life activities selected on the basis of normative data. Within a left
      frontoparietal network, we isolated the medial frontopolar cortex as the only
      region that showed a linear relationship between changes in the blood oxygen
      level-dependent signal and changes in event knowledge complexity. Our results
      specify the importance of the medial frontopolar cortex in subserving event
      knowledge that is required to build and execute complex behavior.

PMID- 19590393
TI  - Distinct neuroinflammatory profile in post-mortem human Huntington's disease.
AB  - Neuroinflammation is a prominent feature of many neurodegenerative diseases,
      however, little is known about neuroinflammation in Huntington's disease. We used
      quantitative real time-PCR to compare the expression level of neuroinflammation
      associated mediators in the striatum, cortex, and cerebellum from post-mortem
      Huntington's disease patient samples with controls. We found increased expression
      of several key inflammatory mediators, including CCL2 and IL-10, specifically in
      the striatum of Huntington's disease patients, the main area affected by this
      pathology. Remarkably, we also found upregulation of IL-6, IL-8, and MMP9, in the
      cortex and notably the cerebellum, a brain area commonly thought to be spared by
      Huntington's disease. Our data suggest that neuroinflammation is a prominent
      feature associated with Huntington's disease and may constitute a novel target
      for therapeutic intervention.

PMID- 19590394
TI  - Long-term cultured skeletal muscle-derived neural precursor cells and their
      neurogenic potentials.
AB  - For cell-based therapy, it is necessary to obtain sufficient cell quantities for
      cell transplantation to the diseased or injured site. However, a given tissue has
      only a limited number of stem cells, making it necessary to expand stem cell
      source through long-term culture. In this study, we evaluated whether our
      recently described skeletal muscle-derived neural precursor (SMNP) cells can be
      cultured long-term without alteration of their neural precursor characteristics.
      Our results showed that SMNP cells can be cultured over approximately 16 months,
      but their growth rate and neurogenic potential gradually decrease in a culture
      time-dependent manner. Importantly, approximately 120-day cultured SMNP cells
      retain their self-renewal ability, neural precursor characteristics, and high
      neurogenic potential. These results suggest that SMNP cells may be an appropriate
      cell source for regenerative or reparative therapies against neuronal disease.

PMID- 19590395
TI  - Transcranial direct current stimulation modulates shifts in global/local
      attention.
AB  - The effects of transcranial direct current stimulation on global/local
      attentional switching and feature processing were assessed. Direct current
      stimulation was applied to the left posterior parietal cortex in 14 healthy
      participants. A compound letter task was used to probe the feature processing and
      the switching of attention between global and local features. Results indicate
      that cathodal stimulation acutely degraded attentional switches during
      stimulation, and anodal stimulation persistently degraded local-to-global
      attentional switching for at least 20 min after stimulation. Direct current
      stimulation had no significant effects on global/local feature processing. These
      results support the functionality of left parietal cortex in attentional switch
      and represent the first successful modulation of global/local switching using
      exogenous brain stimulation.

PMID- 19590396
TI  - Neural process underlying gap detection for spectrally rich and asymmetrical
      markers.
AB  - Processing of silent gaps of the order of milliseconds is crucial in speech
      perception. To investigate such process, we compared gap detection for spectrally
      symmetrical, slightly or widely asymmetrical markers, using the mismatch
      negativity (MMN), an index of preattentive change detection in the brain. The
      slightly asymmetrical markers declined the MMN amplitude alone, but the widely
      asymmetrical markers affected both the MMN amplitude and latency, suggesting that
      the influence of spectrally asymmetrical markers on gap detection is not uniform
      across different magnitude of asymmetries. In contrast to the prevailing view,
      the MMN obtained indicated that the effects of marker asymmetry took place as
      early as at preattentive stage.

PMID- 19590397
TI  - 5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression.
AB  - Genes that regulate the serotonin signalling system are potential targets for
      research in the aetiology of mood disorders and also in the treatment response of
      serotonin reuptake inhibitors. In this study, we evaluated the association of
      seven serotonin signal transduction-linked single nucleotide polymorphisms [HTR1A
      (rs6295), HTR2A (rs6313, rs6311 and rs7997012), HTR6 (rs1805054), TPH1
      (rs1800532) and TPH2 (rs1386494)] with major depressive disorder and/or treatment
      outcome with serotonin reuptake inhibitors. Patients who met the criteria for
      major depressive disorder were treated for 6 weeks with fluoxetine, paroxetine or
      citalopram. The treatment response was evaluated with the Montgomery-Asberg
      Depression Rating Scale, and according to predefined response criteria, the
      patients were divided into responders, nonresponders, remitters and nonremitters.
      Altogether, 86 patients completed the entire study according to the study
      protocol. We had also a control population (N = 395) of healthy blood donors.
      None of the seven single nucleotide polymorphisms was associated with major
      depressive disorder or with treatment response in our study population of Finnish
      individuals.

PMID- 19590406
TI  - Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected
      individuals is associated with higher CD161 expression.
AB  - OBJECTIVE: Natural killer T (NKT) cells are efficiently targeted by HIV and
      severely reduced in numbers in the circulation of infected individuals. The
      functional capacity of the remaining NKT cells in HIV-infected individuals is
      poorly characterized. This study measured NKT cell cytokine production directly
      ex vivo and compared these responses with both the disease status and NKT subset
      distribution of individual patients. METHODS: NKT cell frequencies, subsets, and
      ex-vivo effector functions were measured in the peripheral blood mononuclear
      cells of HIV-infected patients and healthy controls by flow cytometry. We
      measured cytokines from NKT cells after stimulation with either alpha-galactosyl
      ceramide-loaded CD1d dimers (DimerX-alphaGalCer) or phorbol myristate acetate and
      ionomycin. RESULTS: The frequencies of NKT cells secreting interferon-gamma and
      tumor necrosis factor-alpha were significantly lower in HIV-infected patients
      than healthy controls after DimerX-alphaGalCer treatment, but responses were
      similar after treatment with phorbol myristate acetate and ionomycin. The
      magnitude of the interferon-gamma response to DimerX-alphaGalCer correlated
      inversely with the number of years of infection. Both interferon-gamma and tumor
      necrosis factor-alpha production in response to DimerX-alphaGalCer correlated
      inversely with CD161 expression. CONCLUSION: The ex-vivo Th1 responses of
      circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected
      patients. NKT cell functions may be progressively lost over time in HIV
      infection, and CD161 is implicated in the regulation of NKT cell responsiveness.

PMID- 19590407
TI  - Peutz-Jeghers syndrome after oral surgery.

PMID- 19590405
TI  - Expression of latent human immunodeficiency type 1 is induced by novel and
      selective histone deacetylase inhibitors.
AB  - OBJECTIVES: A family of histone deacetylases (HDACs) mediates chromatin
      remodeling, and repression of gene expression. Deacetylation of histones within
      the HIV-1 long terminal repeat (LTR) by HDACs plays a key role in the maintenance
      of latency, whereas acetylation of histones about the LTR is linked to proviral
      expression and escape of HIV from latency. Global HDAC inhibition may adversely
      affect host gene expression, leading to cellular toxicities. Potent inhibitors
      selective for HDACs that maintain LTR repression could be ideal antilatency
      therapeutics. METHODS: We investigated the ability of selective HDAC inhibitors
      to de-repress the HIV-1 LTR in both a cell line model of latency and in resting
      CD4 T cells isolated from patients who were aviremic on antiretroviral therapy
      (ART). RESULTS: We found that inhibition of class I HDACs increased acetylation
      of histones at the LTR, but that LTR chromatin was unaffected by class II HDAC
      inhibitors. In a latently infected cell line, inhibitors selective for class I
      HDACs were more efficient activators of the LTR than inhibitors that target class
      II HDACs. Class I HDAC inhibitors were strikingly efficient inducers of virus
      outgrowth from resting CD4 T cells of aviremic patients, whereas HIV was rarely
      recovered from patient's cells exposed to class II HDAC inhibitors. CONCLUSIONS:
      Further development of selective HDAC inhibitors as part of a clinical strategy
      to target persistent HIV infection is warranted.

PMID- 19590408
TI  - Drug-induced hypersensitivity syndrome with superficial granulomatous dermatitis-
      a novel finding.
AB  - Drug-induced hypersensitivity syndrome (DIHS) is a rare and potentially fatal
      reaction characterized by fever, rash, and internal organ involvement that
      typically occurs between 3 and 6 weeks after commencing the drug. We describe
      such a case in a 26-year-old woman, who developed fever, exfoliative
      erythroderma, facial edema, cervical lymphadenopathy, hepatitis, and leukocytosis
      6 weeks after commencing carbamazepine for lower back pain. Her serum angiotensin
      converting enzyme level was also raised to 144 U/L (8-52 U/L). Skin biopsies
      demonstrated an unusual superficial dermal perivascular inflammatory infiltrate,
      which included conspicuous granulomas mixed with moderate numbers of lymphocytes.
      Eosinophils were not a feature. Her carbamazepine was withdrawn, and oral
      prednisone was commenced initially at a dose of 1 mg.kg.d and slowly weaned over
      a 6-week period. Her fever, rash, facial edema, and hepatitis gradually resolved
      within this period, and her serum angiotensin-converting enzyme level returned to
      within the normal range. Although the patient's clinical course was consistent
      with a DIHS, it was accompanied by a previously unreported finding of a
      superficial granulomatous dermatitis. Granuloma formation as a sequel to
      medication use is a feature of interstitial granulomatous drug reaction. However,
      interstitial granulomatous drug reaction consists of localized violaceous plaques
      with a predilection for skin fold areas and liver function abnormalities have not
      been described. Granulomatous inflammation in other organ systems, including the
      liver and kidney, has also been described after the use of carbamazepine, but
      these reactions are not associated with the systemic manifestations observed in
      DIHS.

PMID- 19590409
TI  - Leprosy: a diagnostic trap for dermatopathologists in nonendemic area.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium leprae,
      presenting with different clinicopathological forms. These great variety of
      presentations make the diagnosis of leprosy a difficult challenge in countries
      where the disease is not endemic. Moreover, a discordance between the clinical
      and histopathological diagnosis in classifying a case of leprosy can complicate
      the issue. We report a 43-year-old woman in whom the diagnosis of leprosy was
      challenging, especially, because the biopsy was sent without any clinical
      suspicion and Italy is a nonendemic area. The clinical informations described
      simply an annular lesion, and histopathology disclosed a superficial and deep
      moderate perivascular and periadnexal infiltrate in the dermis, predominantly
      made of lymphocytes with some histiocytes, in the absence of granuloma formation,
      foamy histiocytes, or giant cells. Only the clinicopathological correlation based
      upon the patient's family history, her Brazilian origin, and her anesthetic
      lesions led us to the suspicion of leprosy. We reviewed the slides with more
      serial cuts and with special stains that eventually revealed a slight perineural
      lymphohistiocytic infiltrate and the presence of rare bacilli in the nerves, more
      consistent with indeterminate leprosy. However, the clinical features and the
      detection of just few bacilli in the skin lesions and skin smears were more
      consistent with a borderline leprosy. The discordance between the clinical and
      histopathological diagnosis in the setting of leprosy is discussed.

PMID- 19590410
TI  - Genitogluteal porokeratosis: 10 years to make the diagnosis!
AB  - Genitogluteal porokeratosis, a relatively rare presentation of porokeratosis of
      Mibelli, often manifests in an atypical way due to its verrucous appearance that
      may obscure the characteristic annular keratotic rim. For this reason,
      misdiagnosis as other common papulosquamous diseases is not uncommon. We report a
      44-year-old man with a 10-year-history of slowly progressive pruritic
      psoriasiform/lichenified plaques over the buttocks. Despite multiple skin
      biopsies, the lesions were misdiagnosed as psoriasis, lichen simplex chronicus,
      pityriasis rubra pilaris, and mycosis fungoides, until the last biopsy revealed
      findings characteristic of porokeratosis. Dermatologists and dermatopathologists
      should be aware of this rare and unique variant of porokeratosis, which, in
      addition to the atypical clinical presentation and the occasional misleading
      histology, may portend a better prognosis in terms of malignant degeneration.

PMID- 19590411
TI  - A rare case of a cutaneous squamomelanocytic tumor: revisiting the histogenesis
      of combined neoplasms.
AB  - We describe what we believe to be the seventh report of a combined tumor with
      histologic features of both malignant melanoma and a squamous cell carcinoma, a
      squamomelanocytic tumor. An 82-year-old woman presented with a nondescript, skin
      colored, firm papule on her nose. Histology showed 2 different neoplastic cell
      proliferations: atypical squamoid cells and irregularly shaped nests of atypical
      pigmented epithelioid cells (melanocytes) arranged in small to large nests at the
      dermal-epidermal junction and within the epidermis. Both components were closely
      admixed and restricted to the epidermis. Immunohistochemistry showed diffuse
      cytoplasmic reactivity for pancytokeratin in all areas supporting the
      histopathologic features of a squamous cell carcinoma. S-100 and melanoma antigen
      recognized by T cells 1 did not stain these areas and showed strong selective
      positivity for the atypical melanocytic component. A true malignant proliferation
      of 2 distinct cell phenotypes due to close paracrine interactions is our favored
      interpretation because of the intimate admixture, distinct immunohistochemical
      pattern, and unique histologic features. Perhaps, chronic sun damage (facial
      location and advanced age) and reduced immunity (history of other malignancies,
      particularly recent history of a basal cell carcinoma) played a complementary
      role for the development of the squamomelanocytic tumor.

PMID- 19590412
TI  - Spiradenocylindrocarcinoma. Report of a case with a low-grade component of
      spiradenocarcinoma and an immunohistochemical study.
AB  - Spiradenocylindrocarcinoma is a very rare malignant cutaneous neoplasm of the
      folliculosebaceous-apocrine unit. We report a case of this hybrid tumor in a 42
      year-old woman. The tumor consisted of 2 circumscribed nodules with areas of
      cylindrocarcinoma and low-grade spiradenocarcinoma. In the overlapping areas,
      both spiradenomatous and cylindromatous features were observed. Expansion of the
      tumor beyond the fibrous pseudocapsule into the adjacent tissue was present.
      Furthermore, tumor cells were demonstrating mild to moderate pleomorphism and an
      increased mitotic index. p53 and ki-67 were among the positive
      immunohistochemical markers. A relatively small number of tumor cells expressed
      estrogen receptors. The aim of this study was to investigate the nature of this
      rare tumor of the skin appendages.

PMID- 19590413
TI  - Giant verrucous nodules in a patient with tuberculosis.
AB  - Sarcoidosis is a systemic inflammatory disorder characterized histologically by
      noncaseating granulomas in affected organs. Cutaneous manifestations of the
      disease such as papules, nodules, plaques, and ulcerations occur in approximately
      25% of the patients. Sarcoidosis can present with multiple different morphologies
      including annular, psoriasiform, ichthyosiform, morpheaform, and verrucous. In
      this study, we report a 30-year-old African American man with a history of spinal
      tuberculosis as a child and slowly enlarging verrucous nodules that appeared at
      the age of 5 years. After an extensive infectious disease evaluation, the
      diagnosis of verrucous sarcoidosis was established with the presence of
      noncaseating granulomas and a completely negative workup for infectious
      etiologies.

PMID- 19590414
TI  - Trichilemmal cyst with carcinoma in situ within an atypical fibroxanthoma.
AB  - A 91-year-old lady presented with an 8-month history of a slow growing keratotic
      nodule on the forehead, which was excised. Histological examination showed a well
      defined lesion with marked cellular pleomorphism. Numerous mitoses were present.
      The cells stained positively with CD10 and CD68 and weakly with smooth muscle
      actin. However, the tumor was negative for cytokeratins (AE1/AE3), epithelial
      membrane antigen (EMA), S100, Melan A, HMB45, leukocyte common antigen (LCA),
      desmin, and CD31. Therefore, the lesion was designated as atypical fibroxanthoma
      (AFX) by exclusion. Within the AFX, there was also a cyst lined by squamous
      epithelium showing pilar keratinization. The epithelium showed full-thickness
      dysplasia with increased mitotic activity and was stained positively with
      AE1/AE3, thus supporting our view of carcinoma in situ within the wall of the
      cyst. To the best of our knowledge, this article describes the first case of
      trichilemmal cyst with carcinoma in situ arising within an AFX.

PMID- 19590415
TI  - Porokeratotic eccrine ostial and dermal duct nevus: a report of 2 cases and
      review of the literature.
AB  - Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare disorder of
      keratinization involving the intraepidermal eccrine duct (acrosyringium). We
      detail two examples of this unique clinicopathological entity--one with a more
      typical clinical presentation and one with a solitary lesion and late adult
      onset. In addition, we discuss the distinctive histologic and immunohistochemical
      findings and review the literature.

PMID- 19590416
TI  - Low-grade B-cell proliferation progressing to high-grade B-cell lymphoma.
AB  - We present a case of a primary cutaneous lymphoproliferative process, originally
      diagnosed as cutaneous lymphoid hyperplasia, which progressed to a nodal high
      grade diffuse large B-cell lymphoma 3 years after the initial diagnosis. The 2
      processes were related by the presence of the same lymphoid clone in the
      cutaneous and the nodal proliferation.

PMID- 19590417
TI  - Dermatoscopy of a primary dermal melanoma.
AB  - This is a case report of a primary dermal melanoma and its dermatoscopic
      findings. A 50-year-old man in 2002 presented on the right anterior aspect of the
      thorax a 1.5-cm-diameter lesion with a rough surface and multiple papules of
      "vascular-like" appearance. It lacked the usual dermatoscopic findings, such as
      atypical pigmented network and radial streaks, related to the infiltration of
      malignant melanoma cells into the epidermis. Papillomatous projections with light
      brown and dark brown blotchy areas were seen under dermatoscopy, due to dermal
      melanin reflection from macrophages and neoplastic melanocytic cells near the
      junctional area. Other areas of papillomatous projections had a light brown-pink
      color surrounded by a thin whitish septum caused by the reflection of dermal
      vessels.

PMID- 19590418
TI  - Viral-associated nonmelanoma skin cancers: a review.
AB  - Nonmelanoma skin cancers are the most common malignancies in the United States,
      with over 1.3 million patients diagnosed yearly. Several types of nonmelanoma
      skin cancer and precancerous lesions have an associated viral pathogenesis,
      including epidermodysplasia verruciformis, verrucous carcinoma, bowenoid
      papulosis, Kaposi sarcoma, squamous cell carcinoma, and, most recently, Merkel
      cell carcinoma. It is now widely accepted that high-risk human papillomaviruses
      (HPVs) play a key role in pathogenesis of cervical and anogenital cancer.
      Currently, 108 types of HPV have been discovered. They can be divided into genera
      including alpha, beta, and gamma HPVs, which comprise the majority of cutaneous
      HPVs. The relationship between viruses and cancer is a popular focus of research
      in an era of AIDS and organ transplantation, where immunosuppression is not
      uncommon. The incidence of viral-related malignancies in these populations is
      increasing. Because of the widespread nature of these cutaneous malignancies, an
      evaluation of these conditions is valuable. This review of the literature will
      focus on the histologic aspects of viral-associated skin malignancies, as well as
      the epidemiology, etiology, and clinical aspects of these diseases.

PMID- 19590420
TI  - Histopathological features in both the eschar and erythematous lesions of
      Tsutsugamushi Disease: identification of CD30+ cell infiltration in Tsutsugamushi
      disease.
AB  - Tsutsugamushi disease is an acute febrile infectious disease caused by Rickettsia
      tsutsugamushi. An infection is heralded by the presence of an eschar at the site
      of the inoculating chigger bite and followed by the development of a disseminated
      erythematous macular rash. CD30 expression is found in anaplastic large cell
      lymphoma; however, expression in nonneoplastic cutaneous disorders, such as
      atopic dermatitis, drug reactions, scabies, and various infectious diseases, has
      also been reported. Study of the cutaneous histopathology of tsutsugamushi
      disease has been limited. In this study, we performed biopsies of both the eschar
      and erythematous lesions of 15 cases of tsutsugamushi disease to assess the
      histopathological changes including the CD3, CD4, CD20, CD30, and CD68
      reactivity. Twelve women and 3 men were included with an age range from 21 to 73
      years. The most common location of the eschar was the trunk (53.3%). The
      histological features showed increased leukocytoclastic vasculitis in the eschar
      (93.3%) compared with the erythematous lesions (33.3%); basal vacuolar changes
      were more common in the erythematous (100%) than in the eschar lesions (20%). The
      inflammatory infiltrate had a majority of CD3- and CD68-positive cells. Seven
      erythematous lesions and 7 eschar lesions showed atypical cells that were CD30
      positive cells. Here, we report on the cutaneous histopathology and pattern of
      inflammatory infiltrates of tsutsugamushi disease. Leukocytoclastic vasculitis
      and basal vacuolar changes were the characteristic features of the eschar and the
      erythematous lesions, respectively. In addition, CD30-positive cell infiltration
      was identified for the first time in this disease.

PMID- 19590419
TI  - Pseudocarcinomatous hyperplasia with follicular differentiation overlying basal
      cell carcinoma.
AB  - We present a series of 25 cases of basal cell carcinoma (BCC) with overlying
      cytologically bland epidermal hyperplasia and cyst formation. Eight of the BCCs
      were nodular and 11 were infiltrative. Immunohistochemical staining for Ki-67 and
      cytokeratin 17 (CK17) was performed to evaluate the proliferative and
      differentiation characteristics of the hyperplastic epithelium compared with the
      adjacent BCC and normal epidermis. Fourteen of the 25 cases had sufficient tissue
      to evaluate the staining patterns. In the majority of cases, Ki-67 expression was
      prominent throughout the BCCs, but only expressed in the basal and suprabasal
      layers of the adjacent hyperplastic epithelium, which was equivalent to normal
      epidermis. CK17 expression was prominent throughout the BCC and surrounding
      incident hair follicles. CK17 was expressed to a lesser extent in the central
      more keratinized portions of the hyperplastic epithelium, but rarely in normal
      epidermis. The morphologic characteristics and immunohistochemical staining
      patterns in these tumors suggest that the epidermal hyperplasia represents
      pseudocarcinomatous hyperplasia with follicular differentiation. Recognizing this
      pattern of epidermal change should alert the pathologist to the possibility of an
      associated BCC in cases in which the biopsy specimen or sectioning is initially
      too superficial to reveal the underlying malignancy.

PMID- 19590421
TI  - Carcinoid-like pattern in melanoma: report of 4 cases.
AB  - Cutaneous melanoma can produce a wide variety of unusual morphological
      appearances, sometimes mimicking other tumors. We report on 4 cases of melanoma
      with carcinoid-like features, namely, arrangement of neoplastic cells in
      trabecules, ribbons, pseudorosettes, rosettes, and/or small round islands. A
      total of 10 biopsies from 4 patients were available for a histopathological study
      comprising congenital nevus, a nodule that had developed in this nevus and its
      persistence/recurrence, 3 primary cutaneous lesions, 3 metastases, and a
      recurrent/persistent lesion. In 7 of these 10 lesions, the most characteristic
      finding was a distinctive arrangement of the neoplastic cells as trabecules,
      ribbons, pseudorosettes, rosettes, or small round insular islands, thus closely
      resembling cell arrangement in carcinoids of various organs. All these tumors
      were positive for melanocytic markers. No neuroendocrine differentiation was
      demonstrated immunohistochemically. We conclude that the carcinoid-like pattern
      in melanoma, namely, the pattern in which neoplastic cells are arranged in
      trabecules, ribbons, cords, rosettes, pseudorosettes, and small round insular
      nests resembling those in carcinoids, is a distinctive pattern, which may rarely
      occur in primary cutaneous melanoma, its recurrence or metastasis, or in a
      melanoma associated with a large congenital nevus. This morphological type of
      melanoma may produce a serious diagnostic pitfall, but despite a confusing
      microscopic appearance, these tumors seem to demonstrate a conventional
      immunohistochemical profile.

PMID- 19590423
TI  - CD1a and factor XIIIa immunohistochemistry in leprosy: a possible role of
      dendritic cells in the pathogenesis of Mycobacterium leprae infection.
AB  - Leprosy is a curable chronic granulomatous infectious disease caused by the
      bacillus Mycobacterium leprae. This organism has a high affinity for skin and
      peripheral nerve cells. In the evolution of infections, the immune status of
      patients determines the disease expression. Dendritic cells are antigen
      presenting cells that phagocytose particles and microorganisms. In skin,
      dendritic cells are represented by epidermal Langerhans cells and dermal
      dendrocytes, which can be identified by expression of CD1a and factor XIIIa
      (FXIIIa). In the present study, 29 skin samples from patients with tuberculoid
      (13 biopsies) and lepromatous (16 biopsies) leprosy were analyzed by
      immunohistochemistry using antibodies to CD1a and FXIIIa. Quantitative analysis
      of labeling pattern showed a clear predominance of dendritic cells in tuberculoid
      leprosy. Difference between the number of positive cells of immunohistochemistry
      for the CD1a and FXIIIa staining observed in this study indicates a role for
      dendritic cells in the cutaneous response to leprosy. Dendritic cells may be a
      determinant of the course and clinical expression of the disease.

PMID- 19590422
TI  - TSC2/PKD1 contiguous gene syndrome: a report of 2 cases with emphasis on
      dermatopathologic findings.
AB  - The association of tuberous sclerosis complex (TSC) and autosomal dominant
      polycystic kidney disease (ADPKD), termed TSC2/PKD1 contiguous gene syndrome, is
      a result of molecular defect demonstrating by deletion disrupting TSC2 and PKD1.
      Dermatopathology of this syndrome has never been addressed. We report 2 sporadic
      cases form of TSC2/PKD1 contiguous gene syndrome, with emphasis on
      dermatopathologic findings. Both patients presented with a typical phenotype of
      TSC and early-onset renal polycystic requiring kidney transplantation in one of
      the patients. Of a total of 13 cutaneous lesions studied, there were 7 facial
      angiofibromas, 2 shagreen patches, 1 periungual fibroma, 1 hypopigmented macule,
      1 epidermoid cyst, and 1 intradermal melanocytic nevus. The histological features
      were basically similar to those occurring in TSC, but some unusual features were
      identified. In both patients, deletions in the region of TSC2 and PKD1 were
      revealed performing by multiplex ligation probe amplification test. It is
      concluded that the histopathological features of skin lesions in this syndrome
      are similar to those encountered in TSC. Clinical awareness and appropriate
      molecular investigation of TSC2/PKD1 contiguous gene syndrome is necessary in all
      patients with a typical phenotype of TSC in infancy, adolescence, or adult age,
      because of severity of the renal alterations.

PMID- 19590424
TI  - Subcutaneous panniculitis-like T-cell lymphoma with overlapping clinicopathologic
      features of lupus erythematosus: coexistence of 2 entities?
AB  - We observed 5 patients with subcutaneous panniculitis-like T-cell lymphoma
      (SPTCL) who were unusual, in that they also exhibited features of lupus
      erythematosus (LE). This observation is in keeping with a recent study that
      reported an increased rate of autoimmune disease, including systemic lupus
      erythematosus (SLE), among patients with SPTCL. In all cases, attributes
      indicating SPTCL included an infiltrate of lymphocytes with pleomorphic nuclei
      involving subcutaneous lobules exhibiting a cytotoxic T-cell (CD3/CD8/betaF1)
      immunophenotype. Additionally, a high proliferation rate and a monoclonal T-cell
      receptor-gamma gene rearrangement were observed in most cases. The manifestations
      of LE in these patients included a spectrum of clinical and histopathological
      abnormalities. Clinical manifestations of LE included, in some patients,
      morphologic evidence of lupus erythematosus panniculitis (LEP) with subcutaneous
      nodules that healed with lipoatrophy on the face. In addition, all the patients
      exhibited serologic and/or extracutaneous end-organ abnormalities seen in
      patients with SLE, with 2 patients having sufficient findings to meet American
      College of Rheumatology criteria for SLE. Histopathological evidence of LE
      included vacuolar change at the dermal-epidermal interface in 3 patients, 2 of
      whom also showed interstitial deposition of mucin in the reticular dermis. One of
      these patients also had findings of LEP in the subcutaneous lobules with clusters
      of CD20 B cells partially arranged within germinal centers. In 2 patients in
      which neither the epidermis nor dermis was available for review,
      histopathological features of LE included, in one patient, a few small clusters
      of CD123 plasmacytoid dendritic cells within the adipose tissue and, in the other
      patient, a positive direct immunofluorescence test (lupus band) on clinically
      uninvolved and lesional skin. Our study shows that some patients show overlap
      between SPTCL and LE. We suspect that these patients may suffer from both
      diseases concomitantly. Furthermore, patients with LE, particularly LEP, should
      be monitored for evolution into SPTCL with biopsy of any subcutaneous lesion that
      is not typical of LEP. Additionally, screening for cutaneous LE and SLE could be
      considered in patients with SPTCL.

PMID- 19590426
TI  - A novel association between polycystic ovary syndrome and Helicobacter pylori.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrinopathies. Chronic infections may increase the risk of infertility.
      Helicobacter pylori infection has been found to be associated with infertility,
      and PCOS is also one of the most common causes of infertility. To the best of our
      knowledge, the possible association between H. pylori seropositivity and PCOS has
      never been investigated. METHODS: We performed a prospective study between a
      group of PCOS subjects and an age-matched group of controls. This prospective
      study included 35 women (mean age, 25 +/- 5 years) with PCOS, selected by using
      revised diagnostic criteria of European Society for Human Reproduction and
      Embryology and the American Society for Reproductive Medicine 2003, who were
      compared with their age-matched control group (50 women; mean age, 26 +/- 5
      years). The 1-step H. pylori test device was used to detect IgG-type antibodies
      to H. pylori in serum, to aid in the diagnosis of H. pylori infection. RESULTS:
      H. pylori seropositivity was found to be significantly higher in the PCOS group
      (PCOS 40%; control 22%; P = 0.007). CONCLUSION: We suggest a possible association
      between H. pylori seropositivity and PCOS. It is early to state that H. pylori is
      a new etiological factor for PCOS or the association of PCOS and H. pylori
      infection is coincidental with these data. Further studies evaluating more
      subjects are required.

PMID- 19590425
TI  - A case of extreme hemodynamic lability and hypocalcemia.
AB  - An epinephrine-secreting pheochromocytoma can present with a confusing picture of
      hemodynamic lability with rapid fluctuations between hypo- and hypertension. They
      are challenging to manage and diagnose. We herein present the case of a 44-year
      old patient who presented with extreme hemodynamic lability due to an epinephrine
      secreting tumor. We discuss the initial management, diagnosis, and definitive
      therapy of this relatively rare type of pheochromocytoma.

PMID- 19590427
TI  - Role of the gastric refluxate in gastroesophageal reflux disease: acid, weak acid
      and bile.
AB  - The role of acid, weak/nonacid, and bile in the genesis of esophageal mucosal
      damage and reflux symptoms is complex. Acid combined with pepsin and unconjugated
      bile acids are critical to the development of esophagitis and Barrett's
      esophagus. Acid alone may be the principal factor in determining the severity of
      esophagitis. Weak acid or nonacid reflux does not cause esophageal damage or
      damage to adjacent organs, such as the larynx or lungs. The primary cause of
      heartburn and regurgitation is acid reflux, but a minority of symptoms (5%-15%)
      can be triggered by weak acid or bile reflux. The role is changed among patients
      on proton pump inhibitors with persistent symptoms, where the majority of
      symptoms are now due to weak acid or bile reflux. The proximal extent of the
      reflux, regardless of its acidity, seems to be the key to reflux symptoms.

PMID- 19590428
TI  - N epsilon-(hexanoyl) lysine, a new oxidative stress marker, is increased in
      metabolic syndrome, but not in obstructive sleep apnea.
AB  - BACKGROUND: It is well known that oxidative stress is induced by metabolic
      syndrome (MetS), leading to cardiovascular diseases. On the other hand,
      obstructive sleep apnea syndrome (OSAS) is frequently complicated with MetS, and
      OSAS is also considered to induce oxidative stress. Thus, we examined the plasma
      and urine markers of oxidative stress and antioxidant status in patients with
      OSAS with or without MetS. METHODS: Sixty-nine Japanese men suspected of having
      OSAS were recruited. We divided all patients into 3 groups: nonobese patients,
      obese patients without MetS, and patients with MetS. Oxidative stress markers,
      plasma and urine 8-hydroxydeoxyguanosine (8-OHdG) and plasma N epsilon-(hexanoyl)
      lysine (HEL), and an antioxidant status marker, plasma total antioxidant status,
      were measured by enzyme-linked immunosorbent assay. RESULTS: The plasma HEL level
      was significantly increased in patients with MetS, whereas neither plasma and
      urine 8-OHdG levels nor plasma total antioxidant status level was different in
      patients with MetS. Furthermore, the plasma HEL level was significantly and
      positively correlated with fasting plasma glucose, serum insulin, and homeostasis
      model assessment-insulin resistance index in all subjects. CONCLUSIONS: The
      oxidative stress is strongly associated with the presence of MetS but not related
      to the presence or severity of OSAS. Furthermore, we demonstrated that the plasma
      concentration of HEL is a more sensitive biomarker of oxidative stress in
      patients with MetS than the plasma and urine levels of 8-OHdG.

PMID- 19590429
TI  - Predictors of Emergency Preparedness and Compliance.
AB  - BACKGROUND:: In response to the evolving nature of potential disasters, both
      human made and natural, this research identifies predictors of individual
      emergency preparedness and compliance with government requests. METHODS:: A
      survey of a nationally representative sample of US adults (1629 respondents)
      revealed which emergency supplies and plans they had in place; their perceived
      level of preparedness and that of their local health care system; the likelihood
      of 7 terrorist and 4 naturally occurring events, whether they would evacuate
      their home; shelter in place at home and work; be quarantined, vaccinated, or
      take medication; and whether they believed that these actions would increase
      their chances for survival. RESULTS:: Having supplies was predicted by being
      male, older, wealthier, and white, living in the western United States, and being
      exposed to national news. Having plans was related to living in the western
      United States, having children, and being exposed to national news. Compliance
      was associated with being female and ill. Holding demographic factors constant,
      preparedness and compliance with government requests were associated with the
      perceived likelihood of a natural but not a terrorist event, the perceived
      efficacy of requested actions, and belief in one's local health care system.
      CONCLUSIONS:: A focus on natural as opposed to terrorist events and people's
      perceived efficacy of emergency actions and local health care systems may
      increase their preparedness and compliance with government requests.

PMID- 19590430
TI  - A comparison of patient acceptance of fingerstick whole blood and oral fluid
      rapid HIV screening in an emergency department.
AB  - BACKGROUND: Although whole blood rapid HIV testing has a greater sensitivity and
      specificity compared with oral fluid (OF) testing, patients prefer HIV testing
      using OF specimen collection. Whether patient preference for noninvasive
      collection methods affects acceptance of HIV screening in clinical practice,
      however, is unknown. OBJECTIVE: To determine whether patient acceptance of
      fingerstick whole blood (FWB) and OF rapid HIV screening differs in an emergency
      department setting. METHODS: From May 1 to June 30, 2007, triage-based testers
      offered rapid HIV screening to patients. OF and FWB tests were available on
      alternate days. Eligible patients were medically stable, > or =15 years of age,
      and not known to be HIV infected. RESULTS: : Two thousand two hundred one
      patients were referred for HIV screening: 1089 on OF days and 1112 on FWB
      screening days. Screening rates with OF and FWB were similar (61.9% vs. 59.1%, P
      = 0.18). Although most reasons why patients declined screening were similar for
      the groups, the specimen collection method was the primary reason for refusal by
      25 patients who declined FWB screening compared with none of the patients who
      declined OF screening. CONCLUSIONS: Among emergency department patients, the
      preference for 1 rapid test collection modality over another has a minimal effect
      on actual screening rates.

PMID- 19590431
TI  - Effects of a rapid peer-based HIV/AIDS educational intervention on knowledge and
      attitudes of high school students in a high-income Arab country.
AB  - INTRODUCTION: In response to low knowledge about HIV and intolerant attitudes
      toward persons living with HIV among Arab university students, a peer-based
      educational intervention was developed and impact evaluated on knowledge and
      attitudes of high school students in 2 of 4 main cities of United Arab Emirates.
      METHODS: Four small teams of final year medical students, 3 female and 1 male,
      were trained. Multistage random sampling selected 14 female and 5 male Arab
      schools, then 56 female and 14 male grade 12 classes in Al Ain and Abu Dhabi. The
      90-minute intervention included a factual presentation and 3 attitude workshops.
      Baseline and postintervention knowledge and attitudes were assessed. Significance
      was tested by McNemar, Wilcoxon signed rank, and multilevel regression tests.
      RESULTS: Response was 99.6%, 1398 females and 505 males. Misconceptions about
      modes of transmission and intolerant attitudes were evident. Mean knowledge score
      improved from 65% to 82% and attitude 51% to 64%, that is, relative increase 26%
      (P < 0.0005). Females had slightly lower baseline knowledge than males but showed
      greater improvement in knowledge and attitudes (P < 0.0005) CONCLUSIONS: Grade 12
      students' knowledge about HIV/AIDS was inadequate and attitudes stigmatizing.
      Peer-based knowledge workshops were effective, especially among females. Concise
      integrated teaching and workshops designed to address key knowledge and
      attitudinal deficiencies can be highly effective.

PMID- 19590433
TI  - The saccade-related local field potentials of the superior colliculus: a
      functional marker for localizing the periventricular and periaqueductal gray.
AB  - This study was intended to investigate the neural signals related to oculomotor
      and visual activity during horizontal saccades in humans and to explore the
      potential of using such signals as a functional marker for localizing the
      periventricular and periaqueductal gray. We recorded the local field potentials
      (LFPs) via implanted electrodes in the rostrolateral part of the periventricular
      and periaqueductal gray in four patients (six electrodes) who underwent deep
      brain stimulation for treatment of neuropathic pain. The functional composition
      of the saccade-related LFPs under different visual conditions was characterized
      using time-frequency analysis, and it was correlated with the anatomic placement
      of the electrodes on the postoperative magnetic resonance images. The magnitude
      of oculomotor signals varied predictably with the proximity of the recording
      electrode to the superior colliculus; the oculomotor activity was represented
      specifically in the alpha (8-13 Hz) and theta (4-8 Hz) bands for saccades and in
      the alpha band for fixation, whereas the visual activity was represented in the
      delta band (1-3 Hz) of the LFPs. The compound LFP signals of the superior
      colliculus embrace the synchronized population activity of multimodalities, which
      can be differentiated in the frequency domain. This is the first time LFP signals
      of the human superior colliculus have been characterized. Such signals may be
      used as a functional marker for electrode placement in the periventricular and
      periaqueductal gray for modulation of pain.

PMID- 19590435
TI  - Prognostic value of neurophysiologic intraoperative monitoring in tethered cord
      syndrome surgery.
AB  - Neurophysiologic intraoperative monitoring is used in surgery for tethered cord
      syndrome. Our objective was to determine if neurophysiologic intraoperative
      monitoring is helpful in identifying which patients will have worsening symptoms
      after surgery. The spinal cord was stimulated before and after untethering until
      a motor response was obtained. The pre- and postoperative neurologic examination
      findings were noted. The motor response thresholds before and after untethering
      were compared using Student t tests. Forty patients were identified; 37 had
      higher motor response thresholds before untethering, whereas in three thresholds
      were higher after untethering. Of the 37 patients, two had worsening of motor
      function. All three patients with higher thresholds after untethering had
      worsening of motor function (P < 0.0001). An increase in the motor response
      threshold after surgical release of tethered cord syndrome indicates possible
      worsening of clinical symptoms. Spinal cord stimulation during tethered cord
      syndrome surgery may help predict neurologic outcome.

PMID- 19590434
TI  - Sample entropy tracks changes in electroencephalogram power spectrum with sleep
      state and aging.
AB  - The regularity of electroencephalogram signals was compared between middle-aged
      (47.2 +/- 2.0 years) and elderly (78.4 +/- 3.8 years) female subjects in wake,
      nonrapid eye movement stages 2 and 3 (S-2, S-3), and rapid eye movement sleep.
      Signals from C3A2 leads of healthy subjects, acquired from polysomnograms
      obtained from the Sleep Heart Health Study, were analyzed using both sample
      entropy (SaEn) and power spectral analysis (delta, theta, alpha, and beta
      frequency band powers). SaEn changed systematically and significantly (P < 0.001)
      with sleep state in both age groups, following the relationships wake > rapid eye
      movement > S-2 > S-3. SaEn was found to be negatively correlated with delta power
      and positively correlated with beta power. Small changes in SaEn seem to reflect
      changes in spectral content rather than changes in regularity of the signal. A
      better predictor of SaEn than the frequency band powers was the logarithm of the
      power ratio (alpha + beta)/(delta + theta). Thus, SaEn seems to reflect the
      balance between sleep-promoting and alertness-promoting mechanisms. SaEn of the
      elderly was larger than that of middle-aged subjects in S-2 (P = 0.029) and rapid
      eye movement (P = 0.001), suggesting that cortical state is shifted toward
      alertness in elderly subjects in these sleep states compared with the middle-aged
      subjects.

PMID- 19590437
TI  - Mesalamine-induced multiple pulmonary cavitary nodules associated with
      cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA).

PMID- 19590436
TI  - Clinical characteristics of patients with anti-Jo-1 antibodies: a single center
      experience.

PMID- 19590432
TI  - Viral interference between hepatitis B, C, and D viruses in dual and triple
      infections in HIV-positive patients.
AB  - OBJECTIVE: To investigate the reciprocal inhibitory effects of hepatitis B virus
      (HBV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) infections in naive and
      previously antiretroviral-experienced HIV-positive patients. DESIGN: This
      retrospective study involved 72 consecutive patients of the Italian Cohort Naive
      Antiretroviral cohort: 21 coinfected with HBV/HCV (group 1BC), 18 infected with
      HBV (group 2B), and 33 infected with HCV (group 3C). METHODS: Viral interference
      between HBV and HCV was assessed by means of the qualitative detection,
      quantification, and genotyping of each virus; HDV infection was assessed by means
      of genomic amplification. RESULTS: Univariate analysis showed that HBV DNA was
      less frequently detected in group 1BC than in group 2B (16 of 21 vs 18 of 18; P =
      0.02), their HBV load was significantly lower (median 3.9 vs 5.4 log10 HBV DNA
      copies/mL; P = 0.002), and they more frequently carried HBV genotype D (12 of 13
      vs 4 of 11; P = 0.0071). HCV RNA was less frequently detected in group 1BC than
      in group 3C (12 of 21 vs 33 of 33; P < 0.0001), and HDV RNA was more frequently
      detected in group 1BC than in group 2B (9 of 21 vs 2 of 18; P = 0.028).
      Multivariate analysis of the HBV-infected subjects showed that the risk of HCV
      coinfection was associated with older age [relative risk 0.28, 95% confidence
      interval (CI): 0.09 to 0.90; P = 0.033 for every 10 years older] and intravenous
      drug use (relative risk 73, 95% CI: 2.4 to >999.999; P = 0.013). The only
      predictor of HBV coinfection in HCV-infected individuals was a lower HCV load
      (relative risk 0.30, 95% CI: 0.11 to 0.79 for every additional log10 HCV RNA; P =
      0.015). CONCLUSION: HBV and HCV showed alternative dominant replication in the
      I.Co.N.A. cohort, with HBV having a more unfavorable effect on HCV replication.

PMID- 19590438
TI  - Treatment of periodontoid pannus with infliximab in a patient with rheumatoid
      arthritis.

PMID- 19590439
TI  - Evaluation of the internet for finding persons with undiagnosed rheumatoid
      arthritis and systemic lupus erythematosus.
AB  - BACKGROUND: The internet is used by many new rheumatology patients before
      visiting a health care provider, and is also used for health education, for
      recruiting study participants, administering surveys, conducting clinical trials,
      data entry and management of multicenter trials, and providing a forum for
      patients to share experiences in chat rooms. The internet has not been used for
      nor evaluated for public health applications. OBJECTIVES: We evaluated the
      internet for early detection and referral of individuals with "typical" early
      symptoms of undiagnosed rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE). METHODS: The websites and selected links identified by
      search terms of typical symptoms were evaluated for health information quality,
      readability, and whether or not the sites prioritized possibilities and suggested
      actions. RESULTS: None of the websites examined were completely suitable for
      finding undiagnosed persons with early RA or SLE. Although the websites had
      accurate information, their reading levels were too high for the average reader,
      and were generally poor in terms of giving a differential diagnosis, prioritizing
      the possibilities and none provided an algorithm for action. CONCLUSIONS:
      Internet sites could be enhanced for early detection and referral. The internet
      has become an important factor in clinical practice and physicians are
      increasingly explaining or responding to the information that their patients find
      on the internet. Our study shows that the information available to individuals
      with undiagnosed RA and SLE is likely to be of little help to them and could
      delay their seeking appropriate attention.

PMID- 19590440
TI  - The preferences for outpatient clinic appointment reminders among rheumatology
      patients.

PMID- 19590441
TI  - The composite DAS Score is impractical to use in daily practice: evidence that
      physicians use the objective component of the DAS in decision making.
AB  - INTRODUCTION AND BACKGROUND: The disease activity score for 28 joints (DAS28) is
      widely used for assessing disease activity in rheumatoid arthritis and its use is
      recommended for establishing the need for anti- tumor necrosis factor drugs,
      according to British Society for Rheumatology guidelines. However, calculation of
      the score requires a laboratory measurement of inflammation (either erythrocyte
      sedimentation rate or C-reactive protein) so that it is not possible to have the
      actual score when the patient seen in the clinic and, therefore, it is not
      possible to make immediate treatment decisions based on the DAS28 score. METHODS:
      This is an audit of clinic-based treatment decisions, collecting data for the
      DAS28 on consecutive patients with rheumatoid arthritis. The nonlaboratory
      elements of the DAS score were completed along with a physician global assessment
      and any treatment decisions were recorded. RESULTS: Data on 100 patients were
      collected. Even when the patients were judged to have active disease by DAS28
      treatment switches or increases were not always made. In logistic regression
      analyses, using treatment increase or switch as the dependent variable, only the
      swollen joint count was significant. CONCLUSION: There is evidence from this
      study that the DAS score is limited in daily clinical practice. In this audit of
      practice treatment, changes seem to be made on objective physician assessments
      rather than patient recorded assessments.

PMID- 19590442
TI  - Abdominal pain in a patient with ankylosing spondylitis under treatment with
      infliximab.
AB  - In patients suffering from ankylosing spondylitis, silent inflammatory bowel
      disease (IBD) is frequent. Furthermore, spondylarthritis may be the first
      manifestation of IBD.We describe the case of a patient suffering from ankylosing
      spondylitis who presented with abdominal pain. The patient had been treated over
      2(1/2) years with infliximab. Although the initial clinical presentation seemed
      to suggest new-onset IBD as the cause of the abdominal pain, it eventuated that
      the patient was suffering from a severe abdominal manifestation of tuberculosis
      likely due to reactivation of latent tuberculosis by the anti-TNF agent.

PMID- 19590443
TI  - Unilateral eosinophilic fasciitis: an under-recognized subtype?
AB  - Symmetric skin thickening of the limbs with deep fascial inflammation is the
      hallmark of eosinophilic fasciitis. We describe a woman who presented with
      unilateral progressive skin thickening. Examination of a full thickness skin
      biopsy revealed an inflammatory process and fascial changes consistent with
      eosinophilic fasciitis. In contrast to other scleroderma mimics, eosinophilic
      fasciitis generally responds rapidly to glucocorticoid therapy. It is possible
      that unilateral eosinophilic fasciitis is under-recognized and can easily be
      misdiagnosed as another scleroderma variant if a full thickness biopsy is not
      reviewed by a dermatopathologist. Recognition of this subtype of eosinophilic
      fasciitis is important given the profound differences in prognosis of
      eosinophilic fasciitis and other scleroderma variants.

PMID- 19590444
TI  - Active and latent tuberculosis in patients with systemic lupus erythematosus
      living in the United States.
AB  - BACKGROUND: The prevalence and clinical course of tuberculosis infection have not
      been well described in patients with systemic lupus erythematosus (SLE) in the
      United States. OBJECTIVE: This study documents the demographic, clinical, and
      laboratory characteristics and outcomes of patients with SLE and latent
      tuberculosis infection (LTBI) or active TB in an ethnically diverse clinic.
      METHODS: We conducted a retrospective review of clinical records of patients with
      SLE followed during 2005 in a county community hospital rheumatology clinic, with
      a large immigrant population. Clinical characteristics were analyzed according to
      the patients' ethnicity, tuberculin skin test (TST) results, and history of
      treatment for latent or active TB. RESULTS: Data regarding a history of active TB
      or TST status were available for 187 of 220 patients seen in 2005 (85%). The
      prevalence of TB infection was highest in patients from TB endemic areas.
      Fourteen patients (7%) had active TB and 33 patients (18%) had LTBI. Among the 6
      patients who developed active TB after the onset of SLE, 2 had pulmonary, 1 had
      extrapulmonary, and 3 had disseminated TB. Laboratory features and treatment
      regimens for SLE were similar in patients with a history of TB infection and in
      patients with a negative TST. CONCLUSIONS: A significant number of patients with
      SLE in a county clinic population in the United States had LTBI or TB. Treatment
      of active TB and latent TB yielded good outcomes with no deaths. US clinicians
      should consider screening SLE patients for LTBI, especially those from TB endemic
      areas.

PMID- 19590446
TI  - Cryoglobulin crystal arthropathy in a patient with multiple myeloma.
AB  - Joint involvement is unusual in patients with monoclonal gammopathies. It has
      been characteristically described as a rheumatoid-like seronegative polyarticular
      erosive arthropathy, which also has been related to crystal deposition of
      cryoglobulins in the synovium and several other tissues. This report describes
      the case of a 57-year-old African American woman with a seronegative
      polyarthritis associated with deposition of nonbirefringent or weakly positive
      birefringent rhomboid-shaped crystals in the synovial fluid. The patient, who was
      subsequently diagnosed with multiple myeloma, showed good clinical response to
      oral and intra-articular corticosteroids. Type II cryoglobulins were identified
      in the serum as well as in the synovial fluid. It is important to consider this
      association as part of the differential diagnosis of a patient with multiple
      myeloma and arthritis.

PMID- 19590445
TI  - Spondyloarthropathy after ampullary carcinoma resection: "post-Whipple" disease.
AB  - The development of bowel-bypass syndrome complicating the Whipple procedure for
      biliary tract carcinoma is described here for the first time. A 56-year-old HLA
      B27 + man, treated with excision of adenocarcinoma of the ampulla of Vater,
      developed an undifferentiated spondyloarthropathy, initially unresponsive to
      nonsteroidal anti-inflammatory drugs and doxycycline, but eventually controlled
      with sulfasalazine and tapered corticosteroids. This condition represents another
      example of a rheumatic syndrome occurring after disruption of gastrointestinal
      tract continuity and likely development of small bowel bacterial overgrowth.

PMID- 19590447
TI  - Relation between adiposity and disease risk factors in Mexican American children.
AB  - OBJECTIVE: Excess adiposity is associated with systemic low-grade inflammation,
      which has been implicated in the pathophysiology of various diseases. The purpose
      of this study was to examine the relation between measures of adiposity and
      disease risk factors in Mexican American children participating in a weight loss
      intervention. SUBJECTS AND METHODS: Boys and girls (N=170; 13.3+/-0.1 year)
      volunteered for additional testing from a larger study that demonstrated
      significant reduction in standardized body mass index. Insulin, C-reactive
      protein, soluble cluster of differentiation 14, glucose, and cholesterol profile
      were assessed. RESULTS: Linear mixed models regression showed that changes in
      adiposity (standardized body mass index and triceps skinfold) were significantly
      related with changes in total cholesterol (P=0.01), triglycerides (P<0.001), C
      reactive protein (P<0.001), insulin (P<0.001), Homeostasis model assessment of
      insulin resistance (P<0.001), and high-density lipoprotein (P<0.001).
      CONCLUSIONS: The relation between measures of adiposity and disease risk factors
      was stable over time in children participating in an exercise/weight loss
      intervention. Also, our findings indicate that reducing adiposity results in an
      improvement of blood disease risk factors in Mexican American children.

PMID- 19590448
TI  - An innovative summer camp program improves weight and self-esteem in obese
      children.
AB  - To determine the potential benefits of a residential summer camp to treat
      childhood obesity, 21 obese, multiethnic children (aged 11.4+/-1.4 years; body
      mass index [BMI] percentile 98.5+/-1.4; BMI z score 2.30+/-0.33) from a diverse
      socioeconomic background were enrolled in a 2-week summer camp program.
      Significant improvements (P<0.04) were observed in self-esteem (+0.27+/-0.33
      point), body weight (-3.7+/-1.2 kg), BMI (-1.60+/-0.48 kg/m), BMI z score (
      0.12+/-0.06), number of curl ups (+10.9+/-21.5), systolic and diastolic blood
      pressure (-10.8+/-13.4 and -9.4+/-5.5 mmHg, respectively), and heart rate (-8.2+/
      12.7 bpm).

PMID- 19590449
TI  - Screening of metabolic syndrome in obese children: a primary care concern.
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in a primary
      care pediatric setting and to collect clinical and biochemical data, allowing for
      a prediction of its presence in a supposedly healthy population. METHODS:
      Belonging to a pediatric population followed by pediatricians of the Italian
      National Health Service, 415 subjects with obesity as a unique selection
      criterion were enrolled. The entire cohort was screened for MS, which was defined
      as the presence of at least 2 other findings out of obesity: fasting
      hyperglycemia, low levels of high-density lipoproteins cholesterol,
      hypertriglyceridemia, and hypertension. RESULTS: The overall prevalence of MS was
      30.8%. Major findings (out of obesity) were low high-density lipoproteins
      cholesterol levels (46.2%), hypertension (23.6%), hypertriglyceridemia (22.2%),
      and fasting hyperglycemia (16.6%). Waist-to-height ratio was the only clinical
      parameter directly related to MS, with the same predictive power of insulin
      resistance. CONCLUSIONS: Metabolic syndrome can be present in a significant
      percentage of "healthy" obese children, and a simple clinical parameter could
      identify at-risk subjects. This observation justifies the development and
      implementation of pediatric networks for obesity screening programs.

PMID- 19590450
TI  - Unusual association between autoimmune hepatitis and severe pyoderma gangrenosum.

PMID- 19590451
TI  - Metabolic syndrome in children and adolescents: prevalence, public health issue,
      and time for initiative.

PMID- 19590452
TI  - Increased prevalence of anti-gliadin antibodies and anti-tissue transglutaminase
      antibodies in children with cerebral palsy.
AB  - AIM AND OBJECTIVE: The aim of the study was to investigate whether there is any
      association between cerebral palsy (CP) and celiac disease (CD) in children.
      PATIENTS AND METHODS: Ninety children between 18 months and 18 years of age
      (median 9 years) with CP were included. Antibodies (IgA and IgG) against gliadin
      (AGA), endomysium (EMA), and tissue transglutaminase (tTG) were measured.
      Children with elevated levels of these antibodies were offered a small-bowel
      biopsy. RESULTS: Thirty-nine children showed an elevated level of 1 or more of
      the tested antibodies (43%). None had raised EMA antibodies. Presence of
      tetraplegia or dyskinesia was associated with increased antibody levels
      (P=0.045), as was a more severe functional type of CP (P=0.008). Children with
      elevated antibodies had a lower body weight (P=0.049), height (P=0.041), and body
      mass index (BMI) (P=0.014). Small-bowel biopsies were performed in 27 out of 39
      children; 1 had CD and 2 had intraepithelial lymphocytosis. CONCLUSIONS: A large
      number of children with CP had elevated AGA and/or anti-tTG. Because these
      elevations were associated with lower weight, height, and BMI, it seemed of
      interest to speculate on how these findings correlated to CP and CD. However, we
      found no correlation between CP and CD.

PMID- 19590453
TI  - Maternal HLA class I compatibility in patients with biliary atresia.
AB  - Biliary atresia (BA) is an inflammatory cholangiopathy of unknown etiology.
      Maternal microchimerism has been identified in the livers of patients with BA. We
      analyzed the human leukocyte antigen (HLA) compatibility between 57 BA patient
      mother pairs and 50 control-mother pairs. The HLA class I matching was
      significantly more frequent in BA pairs (odds ratio [OR]=2.46) than controls.
      Similar results were also found in child-to-mother HLA compatibility (OR=2.16).
      Our results indicate that patients with BA have an immunogenetic histocompatible
      relationship with their mothers, which may result in an increase in maternal
      microchimerism found in BA.

PMID- 19590454
TI  - Italian paediatricians' approach to coeliac disease diagnosis.
AB  - The aim of this study was to investigate the current implementation of the 1990
      ESPGHAN criteria for the diagnosis of celiac disease (CD) in Italy to form a
      foundation for their revision. From September 2006 to March 2007 a nationwide
      questionnaire concerning current diagnostic methods was sent by mail to 54
      Italian centres for the diagnosis of CD, which were distributed across the entire
      national territory. The questionnaire investigated the tests performed,
      diagnostic criteria currently used, and the management of some special cases in
      each centre. Eighty percent of the centres use anti-tissue transglutaminase to
      diagnose CD and anti-endomysium antibodies to confirm the results. Fifty-five
      percent still use anti-gliadin antibodies. A total of 87.5% of centres perform
      HLA typing, especially in first-degree relatives and in unclear diagnosis.
      Regarding histology, 67.5% of centres consider an infiltrative lesion consistent
      with diagnosis of CD. The majority of centres (85%) use the 1990 ESPGHAN criteria
      for both symptomatic and asymptomatic patients, but 80% do not perform a second
      biopsy in asymptomatic cases or a gluten challenge in children younger than 2
      years of age. Furthermore, most centres (72.5%) do not prescribe a gluten-free
      diet to asymptomatic patients with positive serology and normal bowel
      architecture (ie, potential cases), but they do program a careful follow-up. In
      conclusion, ESPGHAN criteria are widely followed by Italian CD centres. However,
      their revision may be useful, but it should be evidence based. Large, multicentre
      studies are greatly needed.

PMID- 19590455
TI  - Association of IL23R p.381Gln and ATG16L1 p.197Ala with Crohn disease in the
      Czech population.
AB  - OBJECTIVES: An association of variants in the genes encoding the interleukin 23
      receptor (IL23R, p.Arg381Gln, rs11209026), and the autophagy-related gene 16-like
      1 (ATG16L1, p.Ala197Thr, rs2241880) with Crohn disease (CD) was identified by
      whole genome association studies, and subsequently confirmed by other works. The
      aim of this study was to assess this association in the Czech population.
      SUBJECTS AND METHODS: In a case-control study 333 patients with CD (137
      paediatric and 196 adult-onset) and 499 unrelated healthy controls were genotyped
      using TaqMan SNP assays. RESULTS: The IL23R p.381Gln allele was protective
      against CD in the Czech population (allelic frequency 3.2% in patients vs 5.5% in
      control subjects; OR 0.56, 95% CI 0.33-0.93, P=0.02). ATG16L1 p.197Ala allele
      conferred increased risk of CD (allelic frequency 60% in patients vs 51% in
      controls; OR 1.25, 95% CI 1.02-1.52, P=0.03). There was no appreciable difference
      in the effect of the associated alleles across the strata of CARD15-conferred
      risk. The IL23R and ATG16L1 variants did not influence the age at diagnosis, and
      in the genotype-phenotype analysis, the only detected association was a weak one
      between IL23R p.381Gln and involvement of the upper gastrointestinal tract
      (uncorrected P=0.031). CONCLUSIONS: We confirmed the role of IL23R and ATG16L1 in
      the CD susceptibility in the Czech population, and found a weak protective effect
      of IL23R p.381Gln against upper gastrointestinal tract involvement.

PMID- 19590457
TI  - Efficacy of endobronchial ultrasound-guided transbronchial needle aspiration of
      hilar lymph nodes for diagnosing and staging cancer.
AB  - INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is used mostly in patients with non-small cell lung cancer (NSCLC) to
      sample mediastinal lymph nodes that are visible on computed tomography (CT). We
      sought to determine the efficacy of EBUS-TBNA in sampling enlarged hilar lymph
      nodes in this patient population. METHODS: From January 2004 to May 2007,
      patients with suspected NSCLC and CT or positron emission tomography (PET)
      imaging demonstrating enlarged (>1 cm) or PET-positive hilar lymph nodes
      underwent EBUS-TBNA. Patients with enlarged central mediastinal nodes were
      excluded. Identifiable lymph nodes at locations 10R, 10L, 11R, and 11L were
      aspirated. All patients underwent subsequent surgical staging or clinical follow
      up as indicated. Diagnoses based on aspirates were compared with those based on
      surgical or clinical results. RESULTS: Of 213 patients evaluated (mean age, 56
      years; 138 men), 188 (mean age, 56.3 years; 120 men) were diagnosed with NSCLC
      and were analyzed. In these patients, 229 lymph nodes, ranging 8 to 20 mm, were
      detected, and all were sampled. Of the 188 patients, 25 had a single enlarged
      node in a contralateral hilar position (N3), 40 had multiple enlarged ipsilateral
      nodes in the N1 position, and 123 had an ipsilateral single enlarged node in the
      N1 position. Overall, diagnostic sensitivity of EBUS-TBNA was 91%, specificity
      was 100%, and the positive predictive value was 92.4%. In the 25 patients with
      contralateral hilar nodes, sensitivity was 66%, specificity was 100%, and the
      positive predictive value was 96%. CONCLUSIONS: No complications occurred. In
      experienced hands, EBUS-TBNA of enlarged hilar lymph visible on CT or hilar nodes
      that are PET scan-positive can provide diagnostic results similar to those for
      central mediastinal nodes.

PMID- 19590456
TI  - Variation in care in pediatric Crohn disease.
AB  - OBJECTIVES: Variation in medical care can be a barrier to improving clinical
      outcomes. We aim to describe the variation in care of Crohn disease as provided
      by a broad sample of pediatric gastroenterologists. METHODS: Two hundred forty
      six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice
      sites starting treatment with either thiopurine or infliximab were studied. We
      assessed variation in diagnostic testing that had been performed to establish the
      diagnosis of Crohn disease and to assess the phenotype, extent, and severity of
      disease. We also assessed variation in initial thiopurine and infliximab dosage
      and in nutritional therapy. RESULTS: Diagnostic studies in which care was uniform
      included complete blood count, performed in 100% of patients, erythrocyte
      sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However,
      imaging of the small bowel had not been performed in 19%, and a stool test for
      pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had
      been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT
      was normal. Nonetheless, even when TPMT was normal, 40% of patients received an
      initial dose of thiopurine that was lower than recommended. Testing for
      tuberculosis before initiating treatment with infliximab was not performed in
      30%. In addition, 36% of severely underweight patients were not receiving a
      multivitamin supplement, supplemental formula, or tube feeding. CONCLUSIONS:
      There is variation in diagnostic and therapeutic interventions in the management
      of pediatric Crohn disease, and gaps exist between recommended and actual care.

PMID- 19590458
TI  - Effects of botanicals and combined hormone therapy on cognition in postmenopausal
      women.
AB  - OBJECTIVE: The aim of this study was to characterize the effects of red clover,
      black cohosh, and combined hormone therapy on cognitive function in comparison to
      placebo in women with moderate to severe vasomotor symptoms. METHODS: In a phase
      II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89
      from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were
      randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg
      conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA), or
      placebo. Participants completed measures of verbal memory (primary outcome) and
      other cognitive measures (secondary outcomes) before and during the 12th
      treatment month. A subset of 19 women completed objective, physiological measures
      of hot flashes using ambulatory skin conductance monitors. RESULTS: Neither of
      the botanical treatments had an impact on any cognitive measure. Compared with
      placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal
      memory measures). This effect just missed statistical significance (P = 0.057) in
      unadjusted analyses but reached significance (P = 0.02) after adjusting for
      vasomotor symptoms. Neither of the botanical treatment groups showed a change in
      verbal memory that differed from the placebo group (Ps > 0.28), even after
      controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led
      to a decrease in immediate digit recall and an improvement in letter fluency.
      Only CEE/MPA significantly reduced objective hot flashes. CONCLUSIONS: Results
      indicate that a red clover (phytoestrogen) supplement or black cohosh has no
      effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens
      some aspects of verbal memory.

PMID- 19590462
TI  - To use or not to use: the clinical use of the title "Doctor" by DNP graduates.

PMID- 19590459
TI  - Menopausal symptoms among breast cancer patients 6 months after diagnosis: a
      report from the Shanghai Breast Cancer Survival Study.
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence of menopausal
      symptoms in relation to treatment modalities in Asian women treated for breast
      cancer. METHODS: A population-based cohort of 5,023 Chinese women aged 25 to 70
      years with primary stage 0 to III breast cancer was identified from a population
      based tumor registry and enrolled in the study approximately 6 months after
      diagnosis. Participants were asked about the occurrence of specific menopausal
      symptoms. Associations between these symptoms and breast cancer treatments were
      evaluated by stratified, multivariate logistic regression. RESULTS: Among women
      with a recent diagnosis of breast cancer, 67.2% of premenopausal women and 46.3%
      of postmenopausal women experienced at least one menopausal symptom, namely, hot
      flashes, night sweats, and/or vaginal dryness. Symptom prevalence among
      postmenopausal women decreased progressively with age at diagnosis (63.3% for
      women aged 51-55 y, 51.5% for women aged 56-60 y, and 34.4% for women aged >65 y;
      P < 0.01). Overall, the highest prevalence of most symptoms occurred in women
      aged 46 to 55 years (P < 0.01). Chemotherapy was positively associated with the
      occurrence of any symptom and with each individual symptom, mainly in
      premenopausal women (adjusted odds ratio [OR] range, 2.2-3.3; P < 0.05 for all).
      Tamoxifen use and immunotherapy were associated with having any symptom and with
      each individual symptom, regardless of menopause status (adjusted OR range, 1.5
      1.8 and 1.3-1.5, respectively; P < 0.05 for all). Women treated before menopause
      were at particularly high risk of experiencing two or more symptoms after
      chemotherapy (OR, 1.77; 95% CI, 1.54-4.98; P interaction = 0.05) compared with
      postmenopausal women. CONCLUSIONS: Menopausal symptoms are prevalent among
      Chinese women recently treated for primary breast cancer. These symptoms are
      associated with age and menopause status at the time of diagnosis, as well as
      with the type of treatment received.

PMID- 19590460
TI  - Trends in healthcare utilization for diarrhea and rotavirus disease in privately
      insured US children <5 years of age, 2001-2006.
AB  - BACKGROUND: To assess impact of the new US rotavirus immunization program
      initiated in 2006, robust baseline data on diarrhea and rotavirus disease burden
      are needed. While several studies have assessed burden in inpatient settings, few
      data are available for emergency department (ED) and outpatient settings.
      METHODS: We used the MarketScan databases, a large claims-based data repository,
      to analyze the health and economic burden of diarrhea-related healthcare
      encounters in children <5 years in inpatient, ED, and outpatient settings from
      2001 to 2006. Because rotavirus testing and coding are not routinely performed,
      rotavirus burden was estimated by calculating excess diarrhea events during
      winter compared with summer baseline (winter residual method). RESULTS: Between
      2001 and 2006, the average annual rate of healthcare utilization for diarrhea was
      1561 per 10,000 children <5 years, with a hospitalization rate of 50 per 10,000,
      ED visit rate of 180 per 10,000, and outpatient visit rate of 1332 per 10,000.
      The winter residual method attributed 53% of inpatient, 41% of ED, and 23% of
      outpatient diarrhea events to rotavirus. By age 5, we estimated that 1 in 74
      children are admitted, 1 in 27 require ED care, and 1 in 7 are treated in
      outpatient settings for rotavirus illness. Median payments for rotavirus in
      inpatient, ED, and outpatient settings were $3135, $332, and $90, respectively.
      CONCLUSIONS: Rotavirus causes substantial health and economic burden in US
      children, especially in ED and outpatient settings. Future monitoring through
      claims-based data sources should allow assessment of rotavirus vaccine impact on
      healthcare utilization for diarrhea.

PMID- 19590463
TI  - Agency for Healthcare Research and Quality Health Care Innovations Exchange.

PMID- 19590464
TI  - Self-organization versus self-management: two sides of the same coin?
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies in the field of complex systems have generated new
      perspectives on management in social organizations such as hospitals. Much of
      this research appears as a natural extension of the cross-disciplinary field of
      systems theory. This is the eighth in a series of articles applying complex
      systems science to the traditional management concepts of planning, organizing,
      directing, coordinating, and controlling. In this article, the author explores
      self-organization as it relates to self-management in complex social
      organizations.

PMID- 19590465
TI  - Realizing the care plan's potential.

PMID- 19590466
TI  - Clinical nursing system and staff composition in Shanghai.

PMID- 19590467
TI  - Testing a work empowerment-work relationship model to explain expertise in
      experienced acute care nurses.
AB  - OBJECTIVE: This study tested the ability of work relationships and work
      empowerment to predict nursing expertise in experienced acute care nurses.
      BACKGROUND: With high patient acuity, constant system changes, and multiple
      changing members of the healthcare team, expert nurses are increasingly important
      to ensure positive patient outcomes in acute care settings. METHOD: This study
      was an exploratory, predictive correlational design with a stratified random
      sample of 115 staff nurses from a large tertiary care center. Data were collected
      on work empowerment, work relationships, and nursing expertise. RESULTS: A
      modified study model was supported in this sample of acute care nurses (R =
      0.258, P = .000) and explained 26% of nurses' reported expertise. CONCLUSION:
      Work relationships explained the largest portion of the variance in nurses'
      reported expertise (16%), more than experience in the specialty (9%) with an
      indirect link between work empowerment and nursing expertise.

PMID- 19590468
TI  - Impact of continuous vigilance monitoring on nursing workflow.
AB  - BACKGROUND: Increasing nursing time in patient care is beneficial in improving
      patient outcomes, but this is proving increasingly difficult with the nursing
      shortage, budgetary constraints, and higher patient acuity. OBJECTIVE: Nursing
      workflow was evaluated after the implementation of a continuous vigilance
      monitoring system to determine if the system enhanced patient-centric nursing
      care. METHODS: Work sampling observations were conducted at 3 hospitals for 6
      categories of nursing activities (direct and indirect nursing, documentation,
      administrative, housekeeping, and miscellaneous) at baseline and at 3 and 9
      months. RESULTS: Statistically significant increases in direct (3 months) and
      indirect nursing care (3 and 9 months) were found, with variability between
      sites. Statistically significant increases at 3 and 9 months for documentation of
      patient care activities and decreases in administrative activities were the most
      consistent findings for all sites. CONCLUSION: Continuous vigilance monitoring
      enhanced patient-centric care with increases in direct and indirect nursing care
      and documentation of those activities.

PMID- 19590469
TI  - Nurse leader mindfulness meditation program for stress management: a randomized
      controlled trial.
AB  - OBJECTIVE: The aim of this study was to rigorously evaluate a brief stress
      management intervention for nurse leaders. BACKGROUND: Despite the nursing
      shortage, evidence-based workplace approaches addressing nurse stress have not
      been well studied. METHODS: Nurse leaders (n = 33) were randomly assigned to
      brief mindfulness meditation course (MMC) or leadership course (control). Self
      report measures of stress were administered at baseline and within 1 week of
      course completion. RESULTS: Among MMC participants, change scores (from baseline
      to postintervention) on several subscales of the Symptom Checklist 90-Revised
      showed significantly more improvement in self-reported stress symptoms relative
      to controls. Mindfulness meditation course participants had significantly more
      improvement in Positive Symptom Distress Index (P = 0.010; confidence interval
      [CI] = -0.483 to -0.073) and Global Severity Index (P = 0.019; CI = -0.475 to 
      0.046) and nearly significantly more improvement in Positive Symptom Total (P =
      0.066; CI = -16.66 to 0.581) compared with controls. CONCLUSION: Results support
      preliminary effectiveness of a 4-week MMC in reducing self-reported stress
      symptoms among nursing leaders.

PMID- 19590470
TI  - Bundling the value of discharge telephone calls and leader rounding.
AB  - Discharge telephone calls made by hospital staff provide invaluable opportunities
      to prevent adverse events, improve quality of care, and increase patient
      satisfaction. Similarly, the effect of rounding on patients can improve clinical
      quality and improve both patient and staff satisfaction. The author discusses how
      the combination of implementing both nurse leader rounding and discharge
      telephone calls simultaneously produced powerful positive outcomes in
      satisfaction and patient quality of care.

PMID- 19590471
TI  - Critical thinking, delegation, and missed care in nursing practice.
AB  - OBJECTIVE: The aim of this study was to understand how nurses use critical
      thinking to delegate nursing care. BACKGROUND: Nurses must synthesize large
      amounts of information and think through complex and often emergent clinical
      situations when making critical decisions about patient care, including
      delegation. METHOD: A qualitative, descriptive study was used in this article.
      FINDINGS: Before delegating, nurses reported considering patient condition,
      competency, experience, and workload of unlicensed assistive personnel (UAP).
      Nurses expected UAP to report significant findings and have higher level
      knowledge, including assessment and prioritizing skills. Successful delegation
      was dependent on the relationship between the RN and the UAP, communication,
      system support, and nursing leadership. Nurses reported frequent instances of
      missed or omitted routine care. CONCLUSION: Findings from this project provide
      insight into factors that influence delegation effectiveness. These can guide
      CNOs and frontline nurse leaders to focus on implementing strategies to mitigate
      the consequence of missed care. Ineffective delegation of basic nursing care can
      result in poor patient outcomes, potentially impacting quality measures,
      satisfaction, and reimbursement for the institution.

PMID- 19590472
TI  - A prospective study of risk factors for pain persisting 4 months after
      hysterectomy.
AB  - OBJECTIVES: Chronic pain after hysterectomy is reported by 5% to 32% of women,
      but it is unknown whether the pain is a result of surgery or can be attributable
      to other factors such as preoperative and postoperative pain, physical, and
      psychosocial status. The aim of this prospective study was therefore to study the
      role of surgery and other possible predictors for pain 4 months after
      hysterectomy. METHODS: Ninety women referred for hysterectomy for benign
      conditions completed the study. The women were interviewed and completed pain
      questionnaires before surgery and after 3 weeks and 4 months. Questions were
      about pain location, intensity, and frequency, as well as medical treatment and
      impact on daily living. In addition, the Short Form-36 General Health Status
      Questionnaire and Coping Strategies Questionnaire were completed before surgery.
      RESULTS: Fifteen women (16.7%) had persistent pain 4 months after hysterectomy.
      In 11 women, the pain resembled their preoperative pain, whereas 4 women had pain
      likely to be related to surgery. Preoperative "pain problems elsewhere" and a
      high "acute postoperative pain intensity" were associated with having pain 4
      months after hysterectomy (P = 0.004 and P = 0.034). A similar tendency was seen
      for preoperative "pelvic pain" (P = 0.059). Women with pain at 4 months reported
      lower quality of life in 4 Short Form-36 subscales and less control of pain
      preoperatively (P < 0.05 and P = 0.023). DISCUSSION: Pain persisting 4 months
      after hysterectomy is most often related to preoperative factors and acute
      postoperative pain. The relative contribution of surgery itself is small.

PMID- 19590473
TI  - Randomized, double blinded comparative trial of intradermal injections of
      lignocaine versus N-saline around the knee to relieve pain in patients awaiting
      total knee replacement.
AB  - OBJECTIVES: We report a randomized, double-blinded comparative study assessing
      the efficacy of local anesthetic with N-saline intradermal blocks around the knee
      to reduce pain and improve patient satisfaction while waiting for a total knee
      joint replacement. METHODS: Patients were offered involvement in this study while
      on the hospital waiting list for a knee replacement. Eligible patients, after
      completing a prestudy assessment, received an average of 6.3 (range: 1 to 10)
      intradermal injections of 0.5 mL either saline or 1% lignocaine injections into
      tender points around the knee. Patients were assessed at 2 hours and 1 week after
      the injections. Pain was assessed using 0 to 100 visual analog pain scale. Global
      perceived effect (satisfaction) was measured on a 7-point Likert scale. RESULTS:
      Thirty-two of 34 patients attended at 1-week assessment, 24 (75%) felt that they
      were improved, and 8 (25%) considered they were unchanged or worse. In both the
      saline and lignocaine groups, 12 of 16 patients felt that they had improved. N
      saline proved as effective as lignocaine in reducing knee pain when injected
      intradermally. Seventy-five percent of patients were improved at 1 week.

PMID- 19590474
TI  - The natural history of complex regional pain syndrome.
AB  - OBJECTIVE: Complex regional pain syndrome (CRPS) is a severe chronic pain
      condition characterized by sensory, autonomic, motor, and dystrophic signs and
      symptoms. This study was undertaken to expand our current knowledge of the
      evolution of CRPS signs and symptoms with duration of disease. METHOD: This was a
      retrospective, cross-sectional analysis using data extracted from a patient
      questionnaire to evaluate the clinical characteristics of CRPS at different time
      points of disease progression. Data from the questionnaire included pain
      characteristics and associated symptoms. It also included autonomic, motor, and
      dystrophic symptoms and also initiating events, ameliorating and aggravating
      factors, quality of life, work status, comorbid conditions, pattern of pain
      spread, family history, and demographics. Comparisons were made of different
      parameters as they varied with disease duration. RESULTS: A total of 656 patients
      with CRPS of at least 1-year duration were evaluated. The average age of all
      participants was 37.5 years, with disease duration varying from 1 to 46 years.
      The majority of participants were white (96%). A total of 80.3% were females.
      None of the patients in this study demonstrated spontaneous remission of their
      symptoms. The pain in these patients was refractory showing only modest
      improvement with most current therapies. DISCUSSION: This study shows that
      although CRPS is a progressive disease, after 1 year, the majority of the signs
      and symptoms were well developed and although many variables worsen over the
      course of the illness, the majority demonstrated only moderate increases with
      disease duration.

PMID- 19590475
TI  - Sensory complaints of the upper extremities in multiple sclerosis: relative
      efficacy of nortriptyline and transcutaneous electrical nerve stimulation.
AB  - OBJECTIVE: The aim of this study was to evaluate the relative efficacy of
      nortriptyline and self-applied transcutaneous electrical nerve stimulation (TENS)
      in the treatment of pain and/or sensory complaints of the upper extremities in
      people with multiple sclerosis (MS). METHODS: A randomized clinical trial
      conducted from September 2005 to September 2006. Fifty-nine people with
      clinically definite MS aged 15 to 50 years were randomly allocated to receive an
      8-week treatment course of either nortriptyline (10 mg daily increment over 1
      week to 50 mg) or self-applied TENS. Response to treatment was assessed at 2, 4,
      and 8 weeks after commencement of the intervention. RESULTS: TENS seemed to be
      equivalent in efficacy to nortriptyline. A significant decrease in visual analog
      scale scores of pain and/or sensory complaints of the upper extremities occurred
      in both groups. Of the 29 people treated with TENS, the mean (SD) intensity of
      pain and/or sensory complaints decreased from 5.3 (1.6) at baseline to 2.8 (1.5)
      at 8 weeks follow-up (P < 0.001). Correspondingly in the 30 people treated with
      nortriptyline, the mean (SD) intensity of pain and/or sensory complaints
      decreased from 4.9 (1.9) to 3.3 (2.1) (P < 0.001). The mean difference in visual
      analog scale score at 8 weeks follow-up was not significant between the 2 groups
      (mean difference -0.5; 95% confidence interval, -1.5-0.5). DISCUSSION: This study
      demonstrates that both nortriptyline and TENS can be effective in reducing the
      intensity of pain and/or sensory complaints in the upper extremities of people
      with MS. However given the side-effect profile of nortriptyline, TENS may have
      some benefits over nortriptyline. This modest reduction in the intensity of pain
      and/or sensory complaints suggests that physicians should carefully weigh the
      risk and benefits of nortriptyline and TENS in people with MS with pain and/or
      sensory complaints.

PMID- 19590476
TI  - Assessment of pain quality in a clinical trial of gabapentin extended release for
      postherpetic neuralgia.
AB  - OBJECTIVE: To replicate and extend previous research concerning the validity and
      utility of using pain quality measures in clinical trials. METHODS: One hundred
      fifty-eight patients with moderate-to-severe postherpetic neuralgia were randomly
      assigned to 1 of 3 treatment conditions: (1) extended release gabapentin (G-ER)
      1800 mg once-daily administered in the evening; (2) G-ER 1800 mg asymmetric
      divided dose (600 mg AM and 1200 mg PM); or (3) placebo G-ER. A measure of
      different pain qualities, the Neuropathic Pain Scale, was administered as a
      secondary measure in this study before, during, and after the treatment. RESULTS:
      The results suggest that G-ER, especially when administered twice-daily, have the
      greatest effects on sharp, dull, sensitive, and itchy pain. Few between-condition
      effects were found for the global ratings of intensity or unpleasantness, and for
      hot, cold, deep, or surface pain qualities. CONCLUSIONS: The results provide
      further support for the importance of assessing specific pain qualities as
      outcomes in clinical trials. The findings may also be used by clinicians for
      identifying those patients for whom G-ER may be particularly effective; that is,
      patients with postherpetic neuralgia presenting with pain described as sharp,
      dull, sensitive, or itchy.

PMID- 19590477
TI  - Experience and management of chronic pain among patients with other complex
      chronic conditions.
AB  - OBJECTIVE: Managing multiple chronic health conditions is a significant
      challenge. The purpose of this study was to examine the experience and management
      of chronic pain among adult patients with other complex chronic conditions,
      specifically diabetes and heart failure (HF). METHODS: We surveyed 624 US
      Department of Veterans Affairs primary care patients in 3 study groups: 184 with
      HF, 221 with diabetes, and 219 general primary care users. We compared health
      status and function between those with and without chronic pain within the 3
      study groups. Among those with chronic pain, we compared pain location, severity,
      and treatment across groups. RESULTS: More than 60% in each group reported
      chronic pain, with the majority reporting pain in the back, hip, or knee. In all
      groups, patients with chronic pain were more likely to report fair or poor health
      than those without pain (P<0.05). In the HF and diabetes groups, a higher
      percentage of patients with pain were not working because of health reasons. Of
      those with pain, more than 70% in each group took medications for pain; more than
      one-half managed pain with rest or sedentary activities; and less than 50% used
      exercise for managing their pain. DISCUSSION: Chronic pain is a prevalent problem
      that is associated with poor functioning among multimorbid patients. Better
      management of chronic pain among complex patients could lead to significant
      improvements in health status, functioning, and quality of life and possibly also
      improve the management of their other major chronic health conditions.

PMID- 19590478
TI  - Comparing diary and retrospective reports of pain and activity restriction in
      children and adolescents with chronic pain conditions.
AB  - OBJECTIVE: The current study investigated the daily relationship between pain,
      activity restriction, and depression in children and adolescents with chronic
      pain, and compared participants' responses on diary and retrospective assessment
      measures. METHOD: Data collection included the administration of diary and
      retrospective measures of pain, activity restriction, and depression to 93
      children with recurrent headache, juvenile chronic arthritis, and sickle cell
      disease. The study used hierarchical linear modeling to examine the relationship
      between daily pain and activity restriction, and analyses compared participants'
      responses on diary and retrospective assessment measures. RESULTS: Using diary
      measures, daily pain intensity was related to children's levels of activity
      restriction. Diary completion was predicted by age and diary-type, with younger
      children and children using electronic diaries demonstrating higher compliance.
      Pain intensity was significantly higher on retrospective compared with diary
      measures, demonstrating inflation in retrospective reports of pain. No
      significant differences between measures of activity restriction emerged.
      DISCUSSION: These preliminary results suggest that although retrospective reports
      of activity restriction may be an acceptable alternative to daily diary
      assessment for children with chronic pain, retrospective measures of pain
      intensity may show inflated pain levels. To provide support for the findings,
      longitudinal research comparing responses to diary versus retrospective measures
      is recommended.

PMID- 19590480
TI  - The national burden of musculoskeletal pain in Japan: Projections to the year
      2055.
AB  - OBJECTIVES: To project the national burdens of low back, hip, and knee pains in
      Japan from 2005 to 2055 in terms of quality adjusted life years (QALYs). METHODS:
      The age- and sex-specific prevalence rates of low back, hip, and knee pains in
      the questionnaire survey (3048 men and 1885 women) were multiplied by the
      corresponding age- and sex-specific Japanese population projections. The losses
      of QALYs associated with low back, hip, and knee pains were calculated as the
      projected numbers of men and women with pain at each site multiplied by the
      corresponding sex-specific mean differences of EQ-5D scores between those who
      reported pain at each site and those who reported no musculoskeletal pain in the
      questionnaire survey. RESULTS: Among a total of 87.9 million Japanese people aged
      30 years or older in 2005, 21.4 million (24.3%), 3.2 million (3.7%), and 9.1
      million (10.4%) were estimated to have low back, hip, and knee pains,
      respectively. The prevalence rates of low back, hip, and knee pains will
      gradually increase in subsequent years, reaching 26.5%, 4.4%, and 12.9%,
      respectively by 2055. Consequently, the losses of QALYs associated with low back,
      hip, and knee pains per 1000 population will increase from 17.2, 3.8, and 8.9,
      respectively in 2005 to 18.8, 4.5, and 11.2, respectively by 2055. DISCUSSION:
      Due to population aging, the national burden of musculoskeletal pain in Japan is
      projected to increase in the next 50 years. Musculoskeletal pain has not been
      counted among national healthcare priorities. However, the control of
      musculoskeletal pain should not be bypassed to improve QOL and extend healthy
      life expectancy.

PMID- 19590479
TI  - Pain in persons living with HIV and comorbid psychologic and substance use
      disorders.
AB  - OBJECTIVES: There is a dearth of information on the experience of pain in persons
      living with human immunodeficiency virus (HIV) and cooccurring psychologic and
      substance use problems. This study examined the prevalence and correlates of pain
      in 162 HIV-positive persons diagnosed with mood and/or anxiety disorders and
      substance use disorders. METHODS: Bodily pain scores in the current sample were
      compared with pain scores in the United States general population and HIV
      positive persons who screened negative for psychologic and substance use
      problems. Bivariate analyses were used to identify significant correlates of pain
      scores in the current sample, which were then subjected to multiple regression
      analysis. RESULTS: Pain scores in the current sample were significantly lower
      (indicating more pain) than the general population and HIV-positive persons who
      screened negative for psychologic and substance use problems. Multivariate
      analysis indicated that the presence of mood disorder, older age, and lower CD4
      cell counts (below 200) were associated with increased pain. Presence of mood
      disorder accounted for the largest amount of unique variance in pain scores.
      DISCUSSION: HIV-positive persons with diagnosed mood/anxiety and substance use
      disorders reported substantially higher levels of pain than the general
      population and HIV-positive persons without these comorbid conditions. The
      presence of mood disorder emerged as an important marker for pain in the current
      sample. Given that individuals living with HIV and comorbid psychologic and
      substance use disorders are at increased risk for pain, concerted efforts should
      be directed at identifying and treating pain in this population.

PMID- 19590481
TI  - Electrical acustimulation of the wrist for chronic neck pain: a randomized, sham
      controlled trial using a wrist-ankle acustimulation device.
AB  - OBJECTIVES: Chronic neck pain is a common problem and is treated using a variety
      of conservative treatments. This single-blind, randomized, sham-controlled trial
      investigated the value of adding electrical stimulation of acupuncture points on
      the wrist to a standardized program of neck exercises for chronic neck pain.
      METHODS: At initial recruitment 60 patients were randomly assigned to receive
      either active or sham electrical stimulation of acupuncture points on the wrist
      in addition to standardized neck exercise. Active or sham wrist acustimulation
      was given for 30 minutes 2 times/wk over a period of 4 weeks. A 30 minutes
      program of standardized neck exercises was also performed simultaneously.
      RESULTS: Forty-nine patients completed the study (22 active, 27 sham).
      Statistically significant improvements were found for acustimulation when
      compared with sham at immediate posttreatment and 1-month posttreatment for
      Numerical Rating Scale, Northwick Park Neck Pain Questionnaire and Pain Self
      Efficacy Questionnaire. In active and sham electrical stimulation group 38.9% and
      8.3% of patients reported a reduction of Numerical Rating Scale > 50% at 1-month
      posttreatment follow-up, respectively. All patients tolerated acustimulation and
      no adverse effects were reported. DISCUSSION: Electrical acustimulation of the
      wrist administered as two, 30 minutes sessions /wk added value to standardized
      neck exercise for chronic neck pain. A 4-week course of treatment produced
      effects lasting 1-month posttreatment.

PMID- 19590482
TI  - Acupuncture in patients with carpal tunnel syndrome: A randomized controlled
      trial.
AB  - OBJECTIVES: To investigate the efficacy of acupuncture compared with steroid
      treatment in patients with mild-to-moderate carpal tunnel syndrome (CTS) as
      measured by objective changes in nerve conduction studies (NCS) and subjective
      symptoms assessment in a randomized, controlled study. METHODS: A total of 77
      consecutive and prospective CTS patients confirmed by NCS were enrolled in the
      study. Those who had fixed sensory complaint over the median nerve and thenar
      muscle atrophy were excluded. The CTS patients were randomly divided into 2
      treatment arms: (1) 2 weeks of prednisolone 20 mg daily followed by 2 weeks of
      prednisolone 10 mg daily (n = 39), and (2) acupuncture administered in 8 sessions
      over 4 weeks (n = 38). A validated standard questionnaire as a subjective
      measurement was used to rate the 5 major symptoms (pain, numbness, paresthesia,
      weakness/clumsiness, and nocturnal awakening) on a scale from 0 (no symptoms) to
      10 (very severe). The total score in each of the 5 categories was termed the
      global symptom score (GSS). Patients completed standard questionnaires at
      baseline and 2 and 4 weeks later. The changes in GSS were analyzed to evaluate
      the statistical significance. NCS were performed at baseline and repeated at the
      end of the study to assess improvement. All main analyses used intent-to-treat.
      RESULTS: A total of 77 patients who fulfilled the criteria for mild-to-moderate
      CTS were recruited in the study. There were 38 in the acupuncture group and 39 in
      the steroid group. The evaluation of GSS showed that there was a high percentage
      of improvement in both groups at weeks 2 and 4 (P < 0.01), though statistical
      significance was not demonstrated between the 2 groups (P = 0.15). Of the 5 main
      symptoms scores (pain, numbness, paresthesia, weakness/clumsiness, nocturnal
      awakening), only 1, nocturnal awakening, showed a significant decrease in
      acupuncture compared with the steroid group at week 4 (P = 0.03). Patients with
      acupuncture treatment had a significant decrease in distal motor latency compared
      with the steroid group at week 4 (P = 0.012). Acupuncture was well tolerated with
      minimal adverse effects. CONCLUSIONS: Short-term acupuncture treatment is as
      effective as short-term low-dose prednisolone for mild-to-moderate CTS. For those
      who do have an intolerance or contraindication for oral steroid or for those who
      do not opt for early surgery, acupuncture treatment provides an alternative
      choice.

PMID- 19590483
TI  - Homeopathic treatment of patients with chronic low back pain: A prospective
      observational study with 2 years' follow-up.
AB  - OBJECTIVES: To evaluate the details and effects of an individualized homeopathic
      treatment in patients with chronic low back pain in usual care. METHODS:
      Prospective multicenter observational study. Consecutive patients beginning
      homeopathic treatment in primary care practices were evaluated over 2 years by
      using standardized questionnaires. Diagnoses (ICD-9) and symptoms with severity,
      health-related quality of life (QoL), medical history, consultations, homeopathic
      and conventional treatments, and other health service use were recorded. RESULTS:
      One hundred twenty-nine adults (64.3% women, mean age 43.6 +/- 12.7 y) were
      treated by 48 physicians. The patients mainly had chronic low back pain (average
      duration 9.6 +/- 9.0 y) and other chronic diseases. Nearly all the patients
      (91.3%) had been pretreated. The initial case-taking took 113 +/- 36, and the
      case analysis took 31 +/- 38 minutes. The 7.4 +/- 8.1 subsequent consultations
      (duration: 23.7 +/- 15.2 min) cumulated to 204.5 +/- 184.6 minutes. The patients
      received an average of 6.8 +/- 6.3 homeopathic prescriptions. The severity of the
      diagnoses and complaints showed marked and sustained improvements with large
      effect sizes (Cohen's d from 1.67 to 2.55) and QoL improved accordingly (SF-36
      physical component scale d = 0.33; mental component scale d = 0.54). The use of
      conventional treatment and health services decreased markedly: the number of
      patients using low back pain-related drugs was half of the baseline. DISCUSSION:
      Classic homeopathic treatment represents an effective treatment for low back pain
      and other diagnoses. It improves health-related QoL and reduces the use of other
      healthcare services.

PMID- 19590484
TI  - The diagnostic accuracy of brief screening questions for psychosocial risk
      factors of poor outcome from an episode of pain: A systematic review.
AB  - OBJECTIVE: To determine the diagnostic accuracy of brief screening questions for
      psychosocial risk factors predictive of poor outcome from an episode of pain.
      METHODS: Six electronic databases were searched, content experts contacted, and
      reference and citation tracking performed. Studies were included that examined
      the diagnostic accuracy of 1-item screening or 2-item screening questions for
      depression, anxiety, fear-avoidance beliefs, social isolation, catastrophization,
      or somatization and were published in English. Studies were assessed for quality,
      and data extracted describing study characteristics and the diagnostic accuracy
      of brief screening questions. RESULTS: Four cross-sectional studies met the
      inclusion criteria and all met 4 or more of our 6 method quality criteria. These
      studies examined the diagnostic accuracy of brief screening tools for depression
      (sensitivity = 50.5% to 82.1%, specificity = 71.0% to 90.6%, and overall accuracy
      = 74.6% to 80.6%) and anxiety (sensitivity 63.0% to 94.0%, specificity = 53.0% to
      71.2%, and overall accuracy = 60.0% to 68.1%). No studies were identified that
      examined the diagnostic accuracy of brief screening questions for fear-avoidance
      beliefs, social isolation, catastrophization, and somatization. DISCUSSION: Data
      were only available on the accuracy of brief screening instruments for depression
      and anxiety, and there was variability in the results. Head-to-head studies are
      required to determine if this variability reflects differential question accuracy
      or population characteristics, and studies that determine the diagnostic accuracy
      of brief screening questions for other common psychosocial risk factors would be
      useful.

PMID- 19590485
TI  - Comparison of ketamine plus midazolam versus ketamine for sedation in children
      during lumbar puncture.

PMID- 19590486
TI  - Chronic abdominal pain as a presentation symptom of Takayasu Arteritis.

PMID- 19590487
TI  - Ketamine and midazolam in combination.

PMID- 19590488
TI  - Acetaminophen safety - deja vu.

PMID- 19590489
TI  - Golimumab (simponi) for inflammatory arthritis.

PMID- 19590490
TI  - Imported human rabies--California, 2008.
AB  - Compared with rabies in developing countries, human rabies is rare in the United
      States, but animal rabies is common. In the United States, most human rabies
      cases are associated with rabid bats, whereas in developing countries, dogs are
      the most common reservoir and vector species. In March 2008, a case of imported
      human rabies in a recently arrived, undocumented Mexican immigrant was laboratory
      confirmed by public health officials in California. The rabies virus isolated
      from the patient was a previously uncharacterized variant most closely related to
      viruses found in Mexican free-tailed bats (Tadarida brasiliensis). The molecular
      and phylogenetic characterizations of this rabies virus variant have been
      described previously. This report summarizes the epidemiologic investigation and
      the ensuing public health response. A total of 20 persons, mostly household
      contacts, received postexposure prophylaxis (PEP) because of potential exposure
      to rabies virus from the patient. The findings underscore the difficulties
      encountered in the diagnosis and epidemiologic investigations of imported human
      rabies cases and the importance of a coordinated public health response across
      multiple international jurisdictions.

PMID- 19590491
TI  - Clinic-based testing for rectal and pharyngeal Neisseria gonorrhoeae and
      Chlamydia trachomatis infections by community-based organizations--five cities,
      United States, 2007.
AB  - CDC recommends screening of at-risk men who have sex with men (MSM) at least
      annually for urethral and rectal gonorrhea and chlamydia, and for pharyngeal
      gonorrhea. Although the standard method for diagnosis is culture, nucleic acid
      amplification (NAA) testing is generally more sensitive and favored by most
      experts. NAA tests have not been cleared by the Food and Drug Administration
      (FDA) for the diagnosis of extragenital chlamydia or gonorrhea and may not be
      marketed for that purpose. However, under U.S. law, laboratories may offer NAA
      testing for diagnosis of extragenital chlamydia or gonorrhea after internal
      validation of the method by a verification study. To determine sexually
      transmitted disease (STD) testing practices among community-based organizations
      serving MSM, CDC and the San Francisco Department of Public Health gathered data
      on rectal and pharyngeal gonorrhea and chlamydia testing at screening sites
      managed by six gay-focused community-based organizations in five U.S. cities
      during 2007. This report summarizes the results of the study, which found that
      three organizations collected samples for NAA testing and three for culture. In
      total, approximately 30,000 tests were performed; 5.4% of rectal gonorrhea, 8.9%
      of rectal chlamydia, 5.3% of pharyngeal gonorrhea, and 1.6% of pharyngeal
      chlamydia tests were positive. These results demonstrate that gay-focused
      community-based organizations can detect large numbers of gonorrhea and chlamydia
      cases and might reach MSM not being tested elsewhere. Public health officials
      could consider providing support to certain community-based organizations to
      facilitate testing and treatment of gonorrhea and chlamydia.

PMID- 19590492
TI  - Progress toward poliomyelitis eradication--India, January 2007-May 2009.
AB  - India is the most populous of the four remaining countries (including
      Afghanistan, Nigeria, and Pakistan) where transmission of wild poliovirus (WPV)
      has never been interrupted. The last cases of WPV type 2 worldwide were reported
      in October 1999 in India. However, transmission of WPV type 1 (WPV1) and WPV type
      3 (WPV3) persists in India in the northern states of Uttar Pradesh and Bihar.
      Transmission of indigenous WPV in all of India's other states was successfully
      interrupted in 2002, and all WPV cases reported since then in the country have
      resulted from WPV circulating in Uttar Pradesh and Bihar. This report updates
      previous reports and summarizes India's progress toward polio eradication since
      January 2007, as of May 29, 2009. In 2005, the government of India introduced the
      use of monovalent oral polio vaccine type 1 (mOPV1), which has higher efficacy
      against WPV1 than does trivalent oral polio vaccine (tOPV), in supplementary
      immunization activities. After a multistate WPV1 outbreak in 2006, preferential
      use of mOPV1 was accelerated and WPV1 cases decreased from 83 in 2007 to 18
      during January-May 2009. A resurgence of WPV3 cases in Uttar Pradesh in 2007 led
      to an outbreak in Bihar. SIAs using monovalent type 3 OPV (mOPV3) were expanded
      in 2007, and the number of WPV3 cases declined from 794 in 2007 to 41 during
      January-May 2009. Simultaneously interrupting transmission in high-risk areas of
      western Uttar Pradesh and Bihar is the key to successful interruption of all WPV
      transmission in India.

PMID- 19590493
TI  - Live imaging of glial cell migration in the Drosophila eye imaginal disc.
AB  - Glial cells of both vertebrate and invertebrate organisms must migrate to final
      target regions in order to ensheath and support associated neurons. While recent
      progress has been made to describe the live migration of glial cells in the
      developing pupal wing (1), studies of Drosophila glial cell migration have
      typically involved the examination of fixed tissue. Live microscopic analysis of
      motile cells offers the ability to examine cellular behavior throughout the
      migratory process, including determining the rate of and changes in direction of
      growth. Paired with use of genetic tools, live imaging can be used to determine
      more precise roles for specific genes in the process of development. Previous
      work by Silies et al. (2) has described the migration of glia originating from
      the optic stalk, a structure that connects the developing eye and brain, into the
      eye imaginal disc in fixed tissue. Here we outline a protocol for examining the
      live migration of glial cells into the Drosophila eye imaginal disc. We take
      advantage of a Drosophila line that expresses GFP in developing glia to follow
      glial cell progression in wild type and in mutant animals.

PMID- 19590494
TI  - Intrakinetochore localization and essential functional domains of Drosophila
      Spc105.
AB  - The kinetochore is assembled during mitotic and meiotic divisions within the
      centromeric region of chromosomes. It is composed of more than eighty different
      proteins. Spc105 (also designated as Spc7, KNL-1 or Blinkin in different
      eukaryotes) is a comparatively large kinetochore protein, which can bind to the
      Mis12/MIND and Ndc80 complexes and to the spindle assembly checkpoint components
      Bub1 and BubR1. Our genetic characterization of Drosophila Spc105 shows that a
      truncated version lacking the rapidly evolving, repetitive central third still
      provides all essential functions. Moreover, in comparison with Cenp-C that has
      previously been observed to extend from the inner to the outer kinetochore
      region, full-length Spc105 is positioned further out and is not similarly
      extended along the spindle axis. Thus, our results indicate that Spc105 forms
      neither an extended link connecting inner Cenp-A chromatin with outer kinetochore
      regions nor a scaffold constraining kinetochore subcomplexes and spindle assembly
      checkpoint components together into a geometrically rigid supercomplex. Spc105
      seems to provide a platform within the outer kinetochore allowing independent
      assembly of various kinetochore components.

PMID- 19590495
TI  - Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal
      integration.
AB  - G protein-coupled receptors (GPCRs) have critical functions in intercellular
      communication. Although a wide range of different receptors have been identified
      in the same cells, the mechanism by which signals are integrated remains elusive.
      The ability of GPCRs to form dimers or larger hetero-oligomers is thought to
      generate such signal integration. We examined the molecular mechanisms
      responsible for the GABA(B) receptor-mediated potentiation of the mGlu receptor
      signalling reported in Purkinje neurons. We showed that this effect does not
      require a physical interaction between both receptors. Instead, it is the result
      of a more general mechanism in which the betagamma subunits produced by the Gi
      coupled GABA(B) receptor enhance the mGlu-mediated Gq response. Most importantly,
      this mechanism could be generally applied to other pairs of Gi- and Gq-coupled
      receptors and the signal integration varied depending on the time delay between
      activation of each receptor. Such a mechanism helps explain specific properties
      of cells expressing two different Gi- and Gq-coupled receptors activated by a
      single transmitter, or properties of GPCRs naturally coupled to both types of the
      G protein.

PMID- 19590496
TI  - Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy.
AB  - The majority of studies on autophagy, a cytoplasmic homeostasis pathway of broad
      biological and medical significance, have been hitherto focused on the
      phosphatidylinositol 3-kinases as the regulators of autophagy. Here, we addressed
      the reverse process driven by phosphoinositide phosphatases and uncovered a key
      negative regulatory role in autophagy of a phosphatidylinositol 3-phosphate
      (PI3P) phosphatase Jumpy (MTMR14). Jumpy associated with autophagic isolation
      membranes and early autophagosomes, defined by the key factor Atg16 necessary for
      proper localization and development of autophagic organelles. Jumpy orchestrated
      orderly succession of Atg factors by controlling recruitment to autophagic
      membranes of the sole mammalian Atg factor that interacts with PI3P, WIPI-1
      (Atg18), and by affecting the distribution of Atg9 and LC3, the two Atg factors
      controlling organization and growth of autophagic membranes. A catalytically
      inactive Jumpy mutant, R336Q, found in congenital disease centronuclear myopathy,
      lost the ability to negatively regulate autophagy. This work reports for the
      first time that initiation of autophagy is controlled not only by the forward
      reaction of generating PI3P through a lipid kinase but that its levels are
      controlled by a specific PI3P phosphatase, which when defective can lead to human
      disease.

PMID- 19590498
TI  - Effects of antihypertensive therapy on cognitive decline in Alzheimer's disease.
AB  - BACKGROUND: Therapeutic trials concerning the effect of antihypertensive therapy
      on cognition have produced controversial findings. Our objective was to evaluate
      the impact of antihypertensive therapy on the cognitive function in subjects
      already diagnosed with Alzheimer's disease (AD). METHODS: We conducted an
      observational study in a memory clinic assessing outpatients suffering from AD. A
      total of 321 patients were included. Cognitive function was assessed yearly by
      the Mini-Mental State Examination (MMSE; score/30). RESULTS: The mean age of
      patients was 78.1 +/- 6 years, 54% of them received antihypertensive therapy and
      the mean MMSE scores were similar in both groups (patients taking
      antihypertensive therapy and patient without antihypertensive therapy). The mean
      follow-up was 34.1 +/- 6 months. MMSE means were significantly higher among
      patients using antihypertensive therapy compared to those without
      antihypertensive therapy (MMSE scores = 21.9 +/- 4.9 vs. 21.2 +/- 5.1 at 1 year
      (P = 0.001); 20.8 +/- 5.5 vs. 19.4 +/- 5.7 at 2 years (P < 0.001); 19.0 +/- 6.7
      vs. 17.5 +/- 6.4 at 3 years (P < 0.001)), after adjustment for age, gender,
      education level, systolic blood pressure (SBP), and diastolic blood pressure
      (DBP) at baseline, MMSE at baseline, coronary heart disease, statins, and
      antiplatelet agents' consumption. Furthermore, the use of antihypertensive
      therapy was associated with a lower estimated risk of cognitive decline (as
      defined by a decrease of at least one point in MMSE score over time) (hazard
      ratio = 0.61; 95% confidence interval = 0.45-0.81) after adjustment for the same
      factors. CONCLUSIONS: These results suggest an association between
      antihypertensive therapy, a lower decrease in mean MMSE and a lower cognitive
      decline over time in AD.

PMID- 19590497
TI  - The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome
      in mice.
AB  - We showed previously that Lyn is a substrate for caspases, a family of cysteine
      proteases, involved in the regulation of apoptosis and inflammation. Here, we
      report that expression of the caspase-cleaved form of Lyn (LynDeltaN), in mice,
      mediates a chronic inflammatory syndrome resembling human psoriasis. Genetic
      ablation of TNF receptor 1 in a LynDeltaN background rescues a normal phenotype,
      indicating that LynDeltaN mice phenotype is TNF-alpha-dependent. The predominant
      role of T cells in the disease occurring in LynDeltaN mice was highlighted by the
      distinct improvement of LynDeltaN mice phenotype in a Rag1-deficient background.
      Using pan-genomic profiling, we also established that LynDeltaN mice show an
      increased expression of STAT-3 and inhibitory members of the NFkappaB pathway.
      Accordingly, LynDeltaN alters NFkappaB activity underlying a link between
      inhibition of NFkappaB and LynDeltaN mice phenotype. Finally, analysis of Lyn
      expression in human skin biopsies of psoriatic patients led to the detection of
      Lyn cleavage product whose expression correlates with the activation of caspase
      1. Our data identify a new role for Lyn as a regulator of psoriasis through its
      cleavage by caspases.

PMID- 19590499
TI  - Soluble CD40 ligand levels in essential hypertensive men: evidence of a possible
      role of insulin resistance.
AB  - BACKGROUND: Elevated levels of the proinflammatory cytokine soluble CD40 ligand
      (sCD40L) were reported in subjects with diabetes, impaired glucose tolerance,
      metabolic syndrome (MS), obesity, and insulin resistance. Metabolic abnormalities
      might also account for increased sCD40L in subjects with essential hypertension.
      METHODS: Several metabolic and vascular correlates of sCD40L levels have been
      investigated in 90 nondiabetic never-treated essential hypertensive men. RESULTS:
      Median sCD40L level was 8.7 ng/ml (interquartile range: 4.9-11.7). On the basis
      of sCD40L, subjects were divided by tertiles (thresholds at 6.6 and 11.0 ng/ml).
      The three groups did not differ for age, body mass index (BMI), smokers, blood
      pressure (BP), prevalence of nondippers, lipids and lipoproteins, renal function,
      and albuminuria. Carotid intima-media thickness (IMT: 0.79 +/- 0.22, 0.83 +/-
      0.29, and 0.85 +/- 0.30 mm) and percentage of subjects with wall thickening (IMT
      >0.9 to <1.3 mm: 23, 27, and 27%, respectively) were superimposable in the three
      groups. No differences were observed in high-sensitivity C-reactive protein (hs
      CRP) and no correlation emerged between sCD40L and hs-CRP. An increase through
      sCD40L tertiles emerged for basal insulin (11.2 +/- 5.6, 14.7 +/- 7.7, and 16.8
      +/- 13.5 microU/ml, P = 0.10) and fasting glucose (95 +/- 11, 103 +/- 16, and 105
      +/- 14 mg/dl, P = 0.028). Consistently, along with the increase in sCD40L, a
      worsening in insulin sensitivity was observed, which was expressed as homeostasis
      model assessment for insulin sensitivity (HOMA%S: 99 +/- 52, 77 +/- 43, and 72 +/
      35, P < 0.05), composite insulin sensitivity index (ISIcomp; Matsuda index: 5.11
      +/- 2.65, 3.61 +/- 1.98, and 3.28 +/- 1.87, P = 0.025), or oral glucose insulin
      sensitivity (OGIS) index (OGIS: 421 +/- 67, 386 +/- 90, and 362 +/- 72, P =
      0.004). CONCLUSIONS: In newly diagnosed hypertensive men, sCD40L levels are
      inversely related to insulin sensitivity, with no correlation with BP, other
      cardiovascular risk factors, or the degree of subclinical atherosclerosis.

PMID- 19590500
TI  - Obesity and depression in US women: results from the 2005-2006 National Health
      and Nutritional Examination Survey.
AB  - Research is needed to better elucidate the relationship between obesity and
      depression, which has been most consistently demonstrated for women, but not for
      men. We examined exclusively a population-based sample of US women who
      participated in the 2005 or 2006 National Health and Nutritional Examination
      Survey. Current depression was defined as having a score of > or =10 (a
      conventional threshold for moderate symptoms of depression) or meeting the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      diagnostic criteria for major depression on the nine-item Patient Health
      Questionnaire. Weight and height were measured and BMI was calculated. Waist
      circumference, a clinical measure of abdominal obesity, was also measured. BMI
      was positively associated with the probability of moderate/severe depressive
      symptoms (r = 0.49, P = 0.03) and major depression (r = 0.72, P < 0.0001). The
      probability curves increased progressively, beginning at BMI of 30. Degree of
      obesity was an independent risk factor for depression even within the obese
      population, and women in obesity class 3 (BMI > or =40) were at particular risk
      (odds ratio (OR) = 4.91, 95% confidence interval (CI): 1.17-20.57), compared to
      those in obesity class 1 (BMI 30 to <35). Abdominal obesity was positively
      associated with depressive symptoms, but not major depression, independent of
      general obesity (BMI). In addition to severe obesity, compromised physical health
      status, young or middle-aged adulthood, low income, and relatively high education
      were also independently associated with greater odds of depressive symptoms among
      obese women. These characteristics may identify specific at-risk subgroups of
      obese women in which hypothesized causal pathways and effective preventive and
      therapeutic interventions can be profitably investigated.

PMID- 19590501
TI  - Racial/ethnic disparities in obesity among US-born and foreign-born adults by sex
      and education.
AB  - This study examines sex and education variations in obesity among US- and foreign
      born whites, blacks, and Hispanics utilizing 1997-2005 data from the National
      Health Interview Survey on 267,585 adults aged > or =18 years. After adjusting
      for various demographic, health, and socioeconomic factors via logistic
      regression, foreign-born black men had the lowest odds for obesity relative to US
      born white men. The largest racial/ethnic disparity in obesity was between US
      born black and white women. High educational attainment diminished the US-born
      black-white and Hispanic-white disparities among women, increased these
      disparities among men, and had minimal effect on foreign-born Hispanic-white
      disparities among women and men. Comprehension of these relationships is vital
      for conducting effective obesity research and interventions within an
      increasingly diverse United States.

PMID- 19590503
TI  - The association between pulse pressure and vascular access thrombosis in chronic
      hemodialysis patients.
AB  - Vascular access thrombosis (VAT) is a major cause of morbidity in chronic
      hemodialysis (HD) patients and is characterized by chronic inflammation. Pulse
      pressure (PP) is positively associated with chronic inflammation. Whether
      patients with high PP are at a higher risk for VAT, however, remains unknown. We
      retrospectively reviewed chronic HD patients with a functional vascular access
      point at the China Medical University Hospital between 1986 and 2005. The
      association between PP and the initial development of VAT at the primary vascular
      access point was examined using the Kaplan-Meier analysis and multivariate Cox
      proportional hazards regression. A total of 576 chronic HD patients (264 men and
      312 women) with a mean age of 56.9+/-14.0 years were reviewed, of whom 145
      (25.2%) experienced at least one episode of VAT. Patients with a PP>60 mm Hg had
      a lower VAT-free survival rate compared with those with a PP<60 mm Hg (P<0.001).
      Using Cox regression with adjustments for age, systolic blood pressure and
      vascular access types, PP (every increase of 10 mm Hg) and serum C-reactive
      protein (CRP) (every increase of 1 mg per 100 ml) were found to be independently
      associated with an increasing risk for VAT, with a hazard ratio of 2.57 (95%
      confidence interval: 1.5-4.4, P=0.001) and 1.14 (95% confidence interval: 1.01
      1.27, P=0.017), respectively. High PP was associated with the development of VAT
      in chronic HD patients. This association was independent of serum CRP levels.

PMID- 19590502
TI  - Variation in the safety of induced pluripotent stem cell lines.
AB  - We evaluated the teratoma-forming propensity of secondary neurospheres (SNS)
      generated from 36 mouse induced pluripotent stem (iPS) cell lines derived in 11
      different ways. Teratoma-formation of SNS from embryonic fibroblast-derived iPS
      cells was similar to that of SNS from embryonic stem (ES) cells. In contrast, SNS
      from iPS cells derived from different adult tissues varied substantially in their
      teratoma-forming propensity, which correlated with the persistence of
      undifferentiated cells.

PMID- 19590504
TI  - Acute cardiovascular effects of the Wenchuan earthquake: ambulatory blood
      pressure monitoring of hypertensive patients.
AB  - An increased incidence of cardiovascular events and sudden death occurs after an
      earthquake. However, the mechanism underlying this is not clear. Previous studies
      attributed this phenomenon to earthquake-induced elevation of sympathetic
      activity. This study investigated the acute cardiovascular effects of the
      Wenchuan earthquake on hypertensive or suspected hypertensive patients. We
      studied the role of earthquake-induced changes in blood pressure and heart rate
      in the occurrence of post-earthquake cardiovascular events. This study included
      11 patients who were undergoing ambulatory blood pressure monitoring when the
      Wenchuan earthquake occurred. Trends in blood pressure and heart rate were
      analyzed, and blood pressure variability (BPV) data were obtained. The mean post
      earthquake blood pressure rose rapidly from 125.8+/-17.3/72.1+/-11.9 to 150.5+/
      20.3/98+/-10.6 mm Hg (average time of first measurement was 13.8+/-6.3 min after
      the first tremor), and blood pressure remained high until 6 h after the
      earthquake. Nighttime blood pressure declined to the mean pre-earthquake daytime
      levels. The mean daytime blood pressure after the earthquake was greater than the
      pre-earthquake daytime mean (systolic blood pressure: 138.9+/-14.6 vs. 129.5+/
      13.6 mm Hg, P=0.009; diastolic blood pressure (DBP): 81.8+/-13.1 vs. 76.9+/-11.9
      mm Hg, P=0.011). Pre- and post-earthquake BPV differed among individuals, but
      circadian variation was absent in all cases and nightly decreases were less than
      10%. These data strongly suggest that significant post-earthquake elevation of
      blood pressure and abnormal circadian variation of blood pressure are related to
      the occurrence of post-earthquake cardiovascular events.

PMID- 19590505
TI  - Direct action of an angiotensin II receptor blocker on angiotensin II-induced
      left atrial conduction delay in spontaneously hypertensive rats.
AB  - In this study, the inhibitory action of angiotensin II (Ang II) receptor blocker
      (ARB) on Ang II-induced conduction blocking in the left atrium was studied.
      Transmembrane action potentials and effective refractory period (ERP) were
      recorded from the left atrial trabeculae of spontaneously hypertensive rats
      (SHR(Izm)s) that had been treated with or without olmesartan medoxomil (AT1
      receptor blocker, 3.0 mg kg(-1)) for 8 weeks before the recording. During rapid
      electrical stimulation (RES), changes in activation time (AT) and frequencies of
      the conduction block were studied under perfusion of Ang II (10(-8) M) or Ang II
      plus ARB (10(-7) M). Interstitial fibrosis in the left atrium was quantitatively
      assessed using histological sections. Although action potential parameters and
      ERP did not differ between the two groups when preparations were driven with a
      basic cycle length, an Ang II-induced conduction delay was observed during RES,
      and this was significantly suppressed in SHR(Izm)s treated with ARB (P<0.05). The
      Ang II-induced conduction block was also significantly reduced with perfusion of
      ARB (P<0.05). The interstitial fibrous area was significantly larger in untreated
      SHR(Izm)s than in treated animals (P<0.01). This antagonizing action of AT1
      blockade might contribute to its non-antiarrhythmic therapeutic effect on atrial
      fibrillation because of its indirect and direct actions on the structural and
      functional remodeling of the left atrium.

PMID- 19590506
TI  - Effect of switching from amlodipine to combination therapy with telmisartan and
      low-dose hydrochlorothiazide.
AB  - One of the most effective pairs in combination therapy is that of an inhibitor of
      the renin-angiotensin system (RAS) and a low-dose thiazide diuretic. Possible
      candidates for this combination therapy are hypertensive patients with blood
      pressure (BP) that is not controlled by a calcium channel blocker (CCB). Thus, we
      characterized the antihypertensive effect of the combination of telmisartan and
      low-dose hydrochlorothiazide in patients with hypertension that was not
      controlled by amlodipine, which is the most common CCB. A total of 75 patients
      with BP levels higher than 140/90 mm Hg, treated with 5 mg per day of amlodipine
      for at least 3 months, were divided into groups that were switched to treatment
      with 40-80 mg per day of telmisartan plus 12.5 mg per day of hydrochlorothiazide
      (TH, n=37) or that were continuously treated with 5-7.5 mg per day of amlodipine
      (Am, n=38). After 12 weeks of treatment, the mean BP level was significantly
      lower in the TH group than in the Am group (decrease in BP: -9.9+/-11.4 vs. 
      3.7+/-8.9 mm Hg, P<0.02; normalization rate: 67.6 vs. 30.3%, P<0.01). Serum uric
      acid was slightly higher in the TH group, but other laboratory data were not
      different between groups. Therefore, it is suggested that the combination of a
      RAS inhibitor and a low-dose thiazide is useful if treatment with a CCB cannot
      control BP in patients with hypertension.

PMID- 19590507
TI  - Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in
      spontaneous hypertensive rats.
AB  - A recent analysis of clinical studies suggests that angiotensin-converting enzyme
      (ACE) inhibitors might reduce bone fractures. In this study, we examined whether
      an ACE inhibitor might attenuate osteoporosis in a hypertensive rat model. In
      spontaneous hypertensive rats (SHRs), estrogen deficiency induced by ovariectomy
      (OVX) resulted in a significant increase in osteoclast activation as assessed by
      the tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied
      by a significant decrease in bone density evaluated by dual-energy X-ray
      absorptiometry and an increase in urinary deoxypyridinoline. Treatment with an
      ACE inhibitor, imidapril, attenuated OVX-induced decrease in bone density and
      increase in TRAP activity and urinary deoxypyridinoline. As ACE inhibitors
      possess the effects of blockade of the renin-angiotensin system (RAS) and
      activation of the bradykinin-nitric oxide pathway, we examined the contribution
      of both pathways in an OVX-induced osteoporosis model. Administration of nitro-L
      arginine methylester (L-NAME) did not alter TRAP activity, urinary
      deoxypyridinoline or bone density, whereas the administration of a subpressor
      dose of angiotensin II accelerated the increase in TRAP activity in the tibia,
      accompanied by a significant decrease in bone density and an increase in urinary
      deoxypyridinoline. Thus, ACE inhibitors prevented osteoporosis, probably because
      of the inhibition of RAS, but not of nitric oxide. Overall, ACE inhibitors
      attenuated osteoporosis in a hypertensive rat model through the blockade of RAS.

PMID- 19590508
TI  - Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation
      independently of the peroxisome proliferator-activated receptor-gamma.
AB  - Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used
      to treat patients with hypertension. Telmisartan, in addition to its effect on
      AT1R, is thought to activate the nuclear transcription factor, peroxisome
      proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial
      PPAR gamma agonist. This study was conducted to examine whether telmisartan might
      suppress cytokine-induced inflammatory signaling in vascular endothelial cells,
      thereby attenuating cellular inflammation possibly by PPAR gamma activation.
      Telmisartan caused a dose-dependent suppression of the tumor necrosis factor
      alpha (TNFalpha)-induced activation of nuclear factor (NF)-kappaB in vascular
      endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not
      influence the inhibitory effect of telmisartan on NF-kappaB activation. The
      thiazolidinediones neither influenced TNFalpha-induced NF-kappaB activation nor
      influenced the inhibitory effect of telmisartan in this process. Telmisartan dose
      dependently diminished the TNFalpha-induced gene expression of VCAM-1, and GW9662
      did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced
      expression of the VCAM-1 gene by blocking NF-kappaB activation independently of
      PPAR gamma activation. Although the mechanism by which this occurs remains
      unclear, our findings suggest that telmisartan-induced anti-inflammatory effects
      might have favorable effects on vasculature in hypertensive patients.

PMID- 19590509
TI  - Job satisfaction of dental practitioners before and after a change in incentives
      and governance: a longitudinal study.
AB  - OBJECTIVES: to measure changes in dental practitioners' job satisfaction
      following a contractual change, and compare differences between those
      transferring from a fee-per-item system (general dental service, GDS) and those
      previously working under a block contract with the primary care trust (personal
      dental service, PDS). DESIGN: Analysis of postal questionnaires conducted in 2006
      and 2007. PARTICIPANTS: Four hundred and forty dental practitioners responding to
      the 2006 baseline questionnaire. RESULTS: Although perceived workload was
      unchanged, global job satisfaction had decreased for 24.7% (31) of GDS dentists
      and 49.0% (95) of PDS dentists comparing their scores given before and after the
      contractual change. PDS dentists showed a significant change in attitudes towards
      feeling restricted in providing quality care (change in factor mean [SD] = -2.88
      [0.82]; p < 0.001). They also showed less positive attitudes towards 'respect'
      (change in factor mean [SD] = -3.70 [0.48]; p < 0.001). CONCLUSIONS: The 2006
      contractual change appears to have had a negative impact on dentists' job
      satisfaction and has not addressed concerns which have led dentists to move into
      the private sector. The study indicates that the fall in job satisfaction is more
      a result of a perceived erosion of professional autonomy than a reaction to the
      change in the system of remuneration.

PMID- 19590511
TI  - p57Kip2 is a repressor of Mash1 activity and neuronal differentiation in neural
      stem cells.
AB  - Mammalian central nervous system (CNS) development is a highly organized process
      involving the precise and coordinated timing of cell-cycle exit, differentiation,
      survival, and migration. These events require proper expression of pro-neuronal
      genes but also repression of alternative cell fates and restriction of cell-type
      specific gene expression. Here, we show that the cyclin-dependent kinase (CDK)
      inhibitor p57Kip2 interacted with pro-neuronal basic helix-loop-helix (bHLH)
      factors such as Mash1, NeuroD, and Nex/Math2. Increased levels of p57Kip2
      inhibited Mash1 transcriptional activity independently of CDK interactions and
      acted as a direct repressor in transcriptional assays. Proliferating
      telencephalic neural progenitors co-expressed basal levels of Mash1 and p57Kip2,
      and endogenous p57Kip2 accumulated transiently in the nuclei of neural stem cells
      (NSCs) during early stages of astrocyte differentiation mediated by ciliary
      neurotrophic factor (CNTF), independent of cell-cycle exit and at times when
      Mash1 expression was still prominent. In accordance with these observations, gain
      and loss-of-function studies showed that p57Kip2 repressed neuronal
      differentiation after mitogen withdrawal, but exerted little or no effect on CNTF
      mediated astroglial differentiation of NSCs. Our data suggest a novel role for
      p57Kip2 as a context-dependent repressor of neurogenic transcription factors and
      telencephalic neuronal differentiation.

PMID- 19590510
TI  - Polypyrimidine tract binding proteins (PTB) regulate the expression of apoptotic
      genes and susceptibility to caspase-dependent apoptosis in differentiating
      cardiomyocytes.
AB  - Cardiac morphologic abnormalities in mice deficient for key regulators of the
      caspase-dependent signaling underscored its role in heart development. However,
      the mechanisms regulating apoptotic gene expression in the developing heart are
      unknown. As polypyrimidine tract binding proteins (PTB) determine gene isoform
      expression during myoblast differentiation and contribute to Apaf-1 translation
      in cell lines, we investigated whether PTB regulate apoptotic gene expression in
      differentiating cardiomyocytes. Our results show that PTB are expressed in the
      embryonic heart and are silenced during development, coinciding with a reduction
      in the expression of apoptotic genes. Overexpression of PTB in postnatal
      cardiomyocytes, which express low levels of PTB and apoptotic genes, induced an
      increase in the amount of pro-apoptotic proteins without affecting abundance of
      their respective transcripts. Translation of the reporter gene Firefly Luciferase
      preceded by the 5'-untranslated region of Apaf-1 or Caspase-3 was enhanced by PTB
      in cardiomyocytes. PTB silencing in fibroblasts induced a decrease of apoptotic
      protein levels. PTB overexpression in cardiomyocytes induced caspase activity and
      caspase-dependent DNA fragmentation during ischemia, which is otherwise caspase
      independent in differentiated cardiomyocytes. Our results show that PTB
      contribute to apoptotic gene expression and modulate the susceptibility to
      caspase activation in differentiating rat cardiomyocytes.

PMID- 19590512
TI  - Suppression of p53 activity by Siva1.
AB  - The tumor suppressor p53 induces potent anti-proliferative responses in stressed
      cells; in unstressed cells this ability of p53 is restrained by Hdm2. Expression
      of Hdm2 is also induced by p53, thereby establishing feedback inhibition.
      Regulation of the p53-Hdm2 interaction and the feedback inhibition of p53 are not
      well understood. Here, we show that the p53-Hdm2 interaction in unstressed cells
      is promoted by Siva1, which, like Hdm2, is the product of a p53 target gene.
      Siva1 binds to both p53 and Hdm2 through distinct regions and enhances Hdm2
      mediated p53 ubiquitination and degradation. Siva1 strongly inhibits p53-mediated
      gene expression and apoptosis. In xenograft mouse models, downregulation of Siva1
      markedly inhibits tumor formation because of the activation of p53. On DNA
      damage, the interactions of Siva1 with both p53 and Hdm2 are diminished. The
      function of Siva1 seems to be related to its ability to form a homo-oligomer as
      the oligomerization defective splicing variant Siva2 fails to de-stabilize p53.
      These results identify Siva1 as an important adaptor promoting p53 degradation
      through Hdm2. Siva1 may be part of the negative feedback loop that inhibits p53
      activity at the end of a non-lethal stress response.

PMID- 19590514
TI  - FGFR2 is associated with hair thickness in Asian populations.
AB  - Hair morphology is one of the most differentiated traits among human populations.
      A previous study has shown that a nonsynonymous single nucleotide polymorphism
      (SNP) in the EDAR gene, EDAR 1540T/C, is strongly associated with hair thickness
      in Asian populations. However, the contributions of other genes remain to be
      elucidated. In this study, 12 SNPs on 10 hair formation-related genes with high
      differentiation between Asian and other populations were examined to further
      identify genes associated with hair morphology. A multiple regression analysis
      adjusted for age, sex, population and the effect of EDAR 1540T/C revealed an SNP
      in intron 9 of FGFR2, rs4752566, to be significantly associated with hair
      thickness (cross-sectional area; P-value=0.0052, small diameter; P-value=0.029
      and large diameter; P-value=0.0015). In the genomic region containing the FGFR2
      gene, rs4752566 was not in strong linkage disequilibrium (LD) with the
      surrounding SNPs, indicating that the significant association of rs4752566 with
      the hair thickness is not due to LD with polymorphisms of the other genes. The
      rs4752566-T allele of FGFR2, associated with thicker hair, was also shown to be
      associated with higher mRNA level of FGFR2 (P-value=0.0270). These results
      suggest that the FGFR2 polymorphism affects the variation in hair thickness in
      Asia through alteration in the expression level of FGFR2.

PMID- 19590513
TI  - XIAP as a ubiquitin ligase in cellular signaling.
AB  - The ability of the vertebrate X-linked inhibitor of apoptosis (XIAP) protein to
      directly suppress apoptotic cell death pathways has been the subject of much
      research. Studies of this broadly expressed protein have largely focused on the
      unique interactions between XIAP and caspases - proteases that conduct and
      participate in the ordered disassembly of the cell during apoptosis. However,
      relatively less attention has been given to the RING domain of XIAP, which
      functions as an E3 ligase to catalyze the ubiquitination of substrate proteins.
      Here, we discuss the evidence implicating the RING domain of XIAP in the
      ubiquitin-mediated regulation of three, somewhat arbitrarily divided, categories
      of substrate: XIAP itself, XIAP-interacting proteins involved in apoptosis, and
      other targets whose physiological roles likely extend beyond cell death.
      Collectively, these multiple activities of XIAP show that this enigmatic protein
      participates in a range of cellular activities beyond apoptotic suppression.

PMID- 19590515
TI  - Association between dopaminergic genes (SLC6A3 and DRD2) and stuttering among Han
      Chinese.
AB  - Normal function of the dopaminergic system is necessary for speech fluency. There
      was evidence that the activities of dopamine transporter (DAT) and dopamine D2
      receptor (DRD2) could be altered in people with speech disfluency. This study
      aims to ascertain the possible correlation between two dopaminergic genes (SLC6A3
      and DRD2) and disorder of speech fluency, and to determine the allelic
      frequencies of the five single-nucleotide polymorphisms (SNPs) (rs2617604,
      rs28364997, rs28364998 in SLC6A3 and rs6275, rs6277 in DRD2) among Han Chinese
      patients with this disorder. A sample of 112 patients with speech disfluency and
      112 gender-matched controls were included in this case-control study. The results
      show that the presence of C allele at rs6277 in DRD2 gene is associated with
      increased susceptibility to the disorder, whereas T allele is protective.
      Haplotype 939T/957T is also a protective factor.

PMID- 19590517
TI  - Evaluation of pupil diameter after posterior chamber phakic intraocular lens
      implantation.
AB  - PURPOSE: To observe the changes of pupil size over time after Visian Implantable
      Collamer Lens (ICL) implantation. PATIENTS AND METHODS: We retrospectively
      examined 30 eyes of 23 consecutive patients undergoing ICL implantation. We
      measured the entrance and real pupil diameters using a Hartmann-Shack aberrometer
      (KR-9000, Topcon, Tokyo, Japan) before and 1 day, 1 week, and 1, 3, 6, and 12
      months after surgery. We also investigated its relationship with the amount of
      vaulting using slit-lamp microscopy 1 year postoperatively. RESULTS: The entrance
      pupil diameters were 6.24+/-0.66 (mean+/-standard deviation) mm preoperatively,
      and 5.53+/-0.69, 6.18+/-0.61, 6.21+/-0.80, 6.29+/-0.74, 6.23+/-0.76, and 6.40+/
      0.70 mm, 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively, respectively;
      and the respective real pupil diameters were 5.44+/-0.55 mm preoperatively, and
      4.95+/-0.60, 5.53+/-0.52, 5.55+/-0.69, 5.63+/-0.64, 5.57+/-0.64, and 5.72+/-0.60
      mm, 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. Pupil diameters
      and the amount of vaulting were not significantly associated (Pearson correlation
      coefficient r=0.14, P=0.45 for entrance pupil, r=0.13, P=0.49 for real pupil).
      CONCLUSIONS: Both pupil diameters decreased transiently 1 day after ICL
      implantation, but soon recovered to the preoperative level, indicating that
      intraoperative mechanical irritation of the uveal tissue and the early
      postoperative inflammatory response may induce transient decreases in pupil
      diameter, and that this surgical technique alone with appropriate ICL size
      selection probably induces no significant pupil diameter change.

PMID- 19590516
TI  - Variable expressivity of ocular associations of foveal hypoplasia in a family.
AB  - PURPOSE: To show the variable expressivity of ocular associations of foveal
      hypoplasia in three affected members of a family. METHODS: Three symptomatic
      members of a family underwent a detailed ophthalmic evaluation including best
      corrected distance and near-vision measurement, colour vision assessment, fundus
      evaluation and fluorescein angiography, horizontal corneal diameter measurement,
      total axial length measurement, and full-field electroretinogram. Optical
      coherence tomography was performed in two of the three cases. Pedigree charting
      was also carried out. RESULTS: Foveal hypoplasia was shown in all three cases.
      Pedigree charting showed an autosomal recessive (AR) inheritance pattern of
      foveal hypoplasia in our series. Microphthalmos and chorioretinal coloboma were
      found to be variably associated with foveal hypoplasia in this series.
      CONCLUSIONS: This interesting case series shows that variable expressivity could
      be found in AR inheritance patterns of foveal hypoplasia.

PMID- 19590518
TI  - Effect of intracameral triamcinolone acetonide on postoperative intraocular
      pressure after cataract surgery.
AB  - PURPOSE: To evaluate the effect of 1 mg intracameral triamcinolone acetonide (TA)
      on postoperative intraocular pressure (IOP) after routine cataract surgery.
      PATIENTS AND METHODS: This prospective, randomized, placebo-controlled study
      comprised 120 eyes of 120 patients with uncomplicated cataract surgery. The
      patients were randomized into two groups. Eyes in group 1 (60 eyes) received an
      injection of 1 mg TA into the anterior chamber at the end of the surgery, but
      eyes in group 2 (60 eyes) did not. The biomicroscopic evaluation, visual acuity
      (VA), and IOP measurements were done at baseline (preoperatively) and 6, 20-24 h,
      1 week, and permonthly until 6 months postoperatively. RESULTS: Mean IOP at 6 and
      20-24 h postoperatively were significantly higher than baseline measurements in
      both groups (P<0.001). Also, the mean IOP values at postoperative 6 and 20-24 h
      were slightly higher in group 1 than in group 2 (P>0.05 for both). The mean IOPs
      at week 1 and 1-6 months after surgery were not significantly different from
      baseline values in both groups (P>0.05 for both time periods). At 6 and 20-24 h
      postoperatively, the number of eyes with an IOP increase>5 and 10 mm Hg with
      respect to baseline were not statistically different between the two groups
      (P>0.05). There were no statistically significant differences in mean VA and the
      amount of anterior chamber cells and flare between the two groups at any
      postoperative visit (P>0.05). CONCLUSION: Intracameral injection of 1 mg TA after
      uncomplicated phacoemulsification surgery had no significant effects on
      postoperative IOP.

PMID- 19590519
TI  - Refractive error and smoking habits in exudative age-related macular degeneration
      in a hospital-based setting.
AB  - PURPOSE: To assess and compare refractive error and smoking habits in patients
      with exudative age-related macular degeneration (AMD) in a clinical setting.
      METHODS: The clinical comparative study included 379 patients (379 eyes) who
      underwent intravitreal application of an anti-vascular growth factor drug for the
      treatment of exudative AMD, and 191 patients without exudative macular
      degeneration and who underwent surgery for age-related cataract. Smoking status
      was compared with an age-matched control group of the German population described
      in the census of 2003. The main outcome measures were refractive error, axial
      length, and data from a questionnaire on smoking habits. RESULTS: The AMD group
      compared with the cataract group showed a significantly shorter axial length
      (23.31+/-0.75 vs 24.20+/-1.56 mm; P<0.001) and was significantly more hyperopic
      (0.65+/-2.14 vs -1.71+/-4.57 dioptres; P<0.001). After the exclusion of
      pseudophakic AMD patients and matching by age and gender, the difference of
      refractive error and axial length between both groups remained to be
      statistically significant (P<0.001). The AMD group and the matched population
      group did not vary significantly in smoking history (age group: 55-75 years,
      current smokers: 18.4% vs 16.8% (P=0.64); former smokers: 23.2% vs 24.9%
      (P=0.66); age group>75 years, current smokers: 6.3% vs 6.4% (P=0.97); former
      smokers: 19.7% vs 22.8% (P=0.25)). CONCLUSIONS: In our setting, an association
      was found between short axial length and AMD. We were not able to confirm the
      previously reported link between smoking and AMD.

PMID- 19590520
TI  - Spectral-domain optical coherence tomography visualisation of retinal oxalosis in
      primary hyperoxaluria.

PMID- 19590521
TI  - OCT measurements on the foveal and perifoveal retinal thickness on diabetic
      patients after phacoemulsification and IOL implantation.
AB  - PURPOSE: The first aim (I.) was to measure the change of macular thickness in
      diabetic (DM group) and nondiabetic patients (NORMAL group), the values of
      operated eye (OP) were compared I.A.) to the fellow, non-operated eye (CONTROL)
      and I.B.) to preoperative baseline value of the operated eye (PRE). The second
      aim (II.) was to compare postoperative macular thickening of DM group to NORMAL
      group eyes. METHODS: Retinal thickness values of the foveal and perifoveal
      (fovea+3.0 mm, fovea+6.0 mm) sectors and the minimum values were measured in a
      prospective study using optical coherence tomography (OCT) in 18 eyes of 18
      diabetic patients and 53 eyes of 53 nondiabetic patients who underwent uneventful
      cataract surgery. Data were collected on the preoperative day and on
      postoperative 1, 7, 30, and 60 days. Student's t-test was used for statistical
      analysis. RESULTS: No significant change of the thickness values could be
      measured one day after surgery. However, a significant increase could be detected
      on the postoperative 7, 30, and 60 days in the perifoveal 3.0 mm and 6.0 mm
      sectors either calculated alone or averaged together with the foveal values. The
      initial (preoperative) average value of 232.7+/-3.5 microm (mean+/-SEM, n=144) in
      the 6.0 mm perifoveal region increased to 246.0+/-8.2 microm (mean+/-SEM, n=120,
      P=0.032) one week, to 249.9+/-5.1 microm (n=112, P=0.017) one month, and to
      249.5+/-6.2 microm (n=104, P=0.009) 2 months after surgery. DISCUSSION: Our
      results indicate that diabetes did not influence significantly the thickening of
      the macular regions after uncomplicated cataract surgery.

PMID- 19590523
TI  - Excimer laser trabeculotomy vs 180 degrees selective laser trabeculoplasty in
      primary open-angle glaucoma. A 2-year randomized, controlled trial.
AB  - PURPOSE: To compare the effectiveness and safety of excimer laser trabeculotomy
      (ELT) ab interno vs selective laser trabeculoplasty (SLT) over 24 months of
      follow-up in patients with primary open-angle glaucoma (POAG) refractory to
      medical therapy. PATIENTS AND METHODS: This prospective, randomized study
      included 30 consecutive eyes assigned randomly to either ELT or SLT group. ELT
      was carried out using a XeCl Excimer Laser with an emission wavelength of 308 nm.
      Eight spots were equally distributed at a distance of 500 microm from one another
      over the anterior trabeculum. The SLT patients were treated with a frequency
      doubled q-switched neodymium:yytrium-aluminum-garnet laser (wavelength 532 nm).
      Approximately 50 adjacent, but not overlapping, laser spots were distributed over
      180 degrees of the trabecular meshwork, using an energy level ranging from 0.7 to
      1.0 mJ per pulse. The main outcome measure was intraocular pressure (IOP)
      lowering after ELT and SLT. Success was defined as >or=20% reduction in IOP
      without further glaucoma intervention. RESULTS: At 24 months, complete success
      rates were 53.3% for the ELT group and 40% for the SLT group (P=0.35, Fisher's
      exact test); qualified success rates were 33.3% for the ELT and 26.6% for the SLT
      group (P=0.5, Fisher's exact test).Mean IOP decreased from 25.0+/-1.9 to 17.6+/
      2.2 mmHg (-29.6%; P<0.0001) in the ELT group and from 23.9+/-0.9 to 19.1+/-1.8
      mmHg (-21%; P<0.0001) in the SLT group. CONCLUSIONS: Both ELT and SLT proved to
      be effective techniques in the treatment of POAG refractory to medical therapy.

PMID- 19590522
TI  - Histopathology and treatment of corneal disease in keratitis, ichthyosis, and
      deafness (KID) syndrome.

PMID- 19590524
TI  - Phospholipid and protein contents of lens proteolipids in human senile cataract.
AB  - PURPOSE: This experimental study was conducted with the aim of evaluating the
      quantitative change, if any, in the phospholipids and protein contents of lens
      proteolipids during cataract formation, and to establish whether the
      phospholipid/protein content of the blood is related to cataractogenesis.
      METHODS: A total of 120 human lenses were collected. Phospholipids and protein
      content in proteolipids of these lenses were estimated biochemically. Blood was
      examined from total 60 persons. Data obtained were analyzed with the help of the
      ANOVA program of SPSS software (version 7.5). RESULTS: A significant (P<0.01)
      reduction of proteolipid-bound phospholipids was observed in cataracts as
      compared with the control lenses. An alteration was also noticed in the protein
      content of proteolipids in the cataractous lenses. Changes were also observed in
      serum total phospholipids (P<0.01) and total protein (P<0.01) in cataractous
      patients. CONCLUSIONS: As proteolipids are the main constituents of the membranes
      of lens fibres, the alterations in its phospholipid and protein moieties may be
      suggestive of the disintegration of lens membranes, which ultimately leads to
      cataract formation. Gradual and constant variation in serum parameters may be one
      of the predisposing factors in cataractogenesis.

PMID- 19590525
TI  - Intravitreal ranibizumab for choroidal neovascularisation secondary to angioid
      streaks.

PMID- 19590526
TI  - Relationship between peripheral visual field loss and vision-related quality of
      life in patients with retinitis pigmentosa.
AB  - PURPOSE: To determine the vision-related quality of life (VRQOL) with the
      National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients
      with retinitis pigmentosa (RP), and to examine the relationship between VRQOL and
      peripheral visual field defects. DESIGN: Prospective study. METHODS: The Japanese
      version of the NEI VFQ-25 was used to study 40 patients with typical RP whose
      visual acuity was >/=0.7 (better than 0.15 in log MAR). For control, 40
      volunteers with normal vision were studied in the same way. The peripheral visual
      field was evaluated by Goldmann's perimetry, and the degree of field loss was
      classified into seven grades. The correlation between the mean of the total
      composite score of the NEI VFQ-25 and the degree of the visual field loss was
      determined. RESULTS: The mean NEI VFQ-25 score was 68.4 in RP patients and 90.1
      in normal controls. This difference was highly significant (P=0.00004). Among RP
      patients, there was a significant negative correlation between the mean NEI VFQ
      25 score and the degree of visual field loss (r=-0.519, P=0.0006). CONCLUSION:
      The significant correlation between the peripheral visual field loss and VRQOL
      score obtained with the NEI VFQ-25, indicates that a good estimate of the QOL can
      be determined by the degree of visual field loss in RP patients.

PMID- 19590527
TI  - The cytotoxic macrolide FD-891 induces caspase-8-dependent mitochondrial release
      of cytochrome c and subsequent apoptosis in human leukemia Jurkat cells.
AB  - The 16-membered macrolide FD-891 exerts cytotoxicity toward several cancer cell
      lines. In this study, we showed that FD-891 induces apoptosis in various human
      cancer cell lines. Human leukemia Jurkat cells were highly sensitive to FD-891,
      exhibiting caspase activation and mitochondrial release of cytochrome c into the
      cytosol at early time points after exposure to FD-891. By contrast, Jurkat cells
      deficient in caspase-8 were resistant to FD-891-induced apoptosis and manifested
      little induction of cytochrome c release as well as caspase-9 processing.
      Consistent with these results, the overexpression of the Bcl-2 family member Bcl
      x(L) or the caspase-8 modulator c-FLIP(L) markedly prevented FD-891-induced
      apoptosis. These results clearly demonstrate that FD-891 triggers caspase-8
      dependent mitochondrial release of cytochrome c and subsequent apoptosis in
      Jurkat cells.

PMID- 19590528
TI  - Activated Ras signaling significantly enhances reovirus replication and spread.

PMID- 19590529
TI  - Downregulation of the coxsackie and adenovirus receptor in cancer cells by
      hypoxia depends on HIF-1alpha.
AB  - Loss of the coxsackie and adenovirus receptor (CAR) has been found in various
      human cancers. Underlying mechanisms, however, are still poorly understood.
      Therefore, the objective of this study was to investigate the function of
      hypoxia, a ubiquitous phenomenon in carcinomas, in CAR regulation. In our
      approach, hypoxia and treatment with cobalt-(II)-chloride (CoCl(2)) induced a
      downregulation of CAR protein and mRNA expression, as well as a suppression of
      CAR gene promoter activity in AGS (gastric), SW480 (colon) and PC3 (prostate)
      cancer cells. In line with these findings we noted a decreased adenoviral uptake
      under hypoxic conditions. Aiming to further elucidate the molecular basis of this
      observation, a full-length hypoxia-inducible factor-1alpha (HIF-1alpha) cDNA was
      ectopically overexpressed in the AGS cell line diminishing CAR expression and CAR
      gene promoter activity. In line with these findings, exposure of HIF-1alpha
      deficient AGS cells to hypoxia did not alter CAR mRNA expression level. On the
      basis of these data, it may be suggested that loss of CAR in human cancer cell
      lines under hypoxic conditions occurs in an HIF-1alpha-dependent manner.

PMID- 19590531
TI  - Stainless Steele and heavy metal health.

PMID- 19590530
TI  - The macrophage marches on its phagosome: dynamic assays of phagosome function.
AB  - Professional phagocytes ingest particulate material to fulfil a diverse array of
      functions in a multicellular organism. The ancestral function of phagosomes is
      digestion; however, through evolution this degradative capacity has become
      pivotal to the adaptive immune response by processing antigens to be presented to
      lymphocytes. Moreover, phagocytes have also acquired an active role in microbial
      killing. This Innovation article describes new assays that probe the biological
      activities which occur within phagosomes. These assays provide functional
      insights into how the phagosome fulfils its diverse roles in homeostasis and in
      innate and adaptive immune responses.

PMID- 19590532
TI  - Growing disbelief.

PMID- 19590533
TI  - Elder abuse.

PMID- 19590534
TI  - Hygiene controls.

PMID- 19590535
TI  - Clarified elevators.

PMID- 19590537
TI  - Government and profession urged to take forward recommendations in new dentistry
      review.

PMID- 19590540
TI  - Change in law over emergency prescribing.

PMID- 19590548
TI  - Who cares for the carers?
AB  - The NHS complaints system has been overhauled again in England with the stated
      aim of simplifying a 'process' driven system and to give 'organisations greater
      flexibility to respond and encourage a culture that seeks and then uses people's
      experiences of care to improve quality'. The complaints system that ran from 1996
      to 31 March 2009 was considered 'too prescriptive and inflexible and not meeting
      the needs of the person making the complaint'. Many fine words and hours of
      consultations have been devoted to analysing the problems with the complaints
      systems and the advantages of producing a new one that enables health services to
      listen to the patients, respond to their concerns and improve the services
      delivered. This patient-centred focus is the new rally cry in the modern twenty
      first century NHS. Very little thought, however, appears to have been given to
      those against whom the complaints are invariably directed: the dentist and their
      teams. What will the new reforms, with one less layer of complaints management
      (the Healthcare Commission) do to the dynamics of complaints management? What
      effects on the dentist and their teams will come about as a result of the primary
      care trust's ability to investigate the complaint themselves if invited to do so
      by the patient?

PMID- 19590549
TI  - Digital dental photography. Part 5: lighting.
AB  - Effective lighting is the key to success in all photography but particularly in
      dental photography. This part of the series on digital dental photography
      examines the colour/space/time triad which is achieved by the presence and
      manipulation of light, be it daylight, flashlight or other forms of illumination.
      In addition, the effect of reflectors is described as well as their effects on
      colour temperature.

PMID- 19590550
TI  - Numbness of the ear following inferior alveolar nerve block: the forgotten
      complication.
AB  - This article presents a distant complication in the auricle following the
      administration of a standard inferior alveolar nerve block. The patient
      experienced profound numbness of the auricle on the ipsilateral side of the
      injection that lasted for about an hour following unintended injection to the
      auriculotemporal nerve.

PMID- 19590551
TI  - Cone beam CT in dental practice.
AB  - Cone Beam Computed Tomography is a relatively new three-dimensional imaging
      technology, which has been specifically developed for imaging of the teeth and
      jaws. The aim of this paper is to acquaint the dental team with various forms of
      this technology and its potential applications. An understanding of the
      underlying principles will allow the users of this technology to tailor the
      imaging protocol to the patient's individual needs to achieve appropriate imaging
      at the lowest radiation dose.

PMID- 19590577
TI  - Overgrowth of a mouse model of Simpson-Golabi-Behmel syndrome is partly mediated
      by Indian hedgehog.
AB  - Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson-Golabi-Behmel
      overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null
      mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog
      (Hh) signalling by inducing its endocytosis and degradation. Here, we show that
      the developmental overgrowth observed in Gpc3-null mice is, at least in part, a
      consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with
      mice that are Hh signalling-deficient owing to the lack of Indian Hh (Ihh), one
      of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9%
      overgrowth in an Ihh wild-type background, whereas an Ihh-null background partly
      rescues the overgrowth caused by the lack of Gpc3 as the double mutants were
      19.8% bigger than the Ihh-null mice. Consistent with the role of GPC3 in Hh
      endocytosis and degradation, the Gpc3-null mice show increased levels of Ihh
      protein and signalling, but similar levels of Ihh messenger RNA.

PMID- 19590578
TI  - DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to
      activate NF-kappaB.
AB  - Detection of viral nucleic acids is central to antiviral immunity. Recently,
      DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified
      as a cytoplasmic DNA sensor and shown to activate the interferon regulatory
      factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors,
      leading to type-I interferon production. DAI-induced IRF activation depends on
      TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular
      components involved in NF-kappaB activation remain elusive. Here, we report the
      identification of two receptor-interacting protein (RIP) homotypic interaction
      motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI
      induced NF-kappaB signals through the recruitment of the RHIM-containing kinases
      RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI
      induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by
      the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings
      delineate the DAI signalling pathway to NF-kappaB and suggest a possible new
      immune modulation strategy of the MCMV.

PMID- 19590579
TI  - The SPX domain of the yeast low-affinity phosphate transporter Pho90 regulates
      transport activity.
AB  - Yeast has two phosphate-uptake systems that complement each other: the high
      affinity transporters (Pho84 and Pho89) are active under phosphate starvation,
      whereas Pho87 and Pho90 are low-affinity transporters that function when
      phosphate is abundant. Here, we report new regulatory functions of the amino
      terminal SPX domain of Pho87 and Pho90. By studying truncated versions of Pho87
      and Pho90, we show that the SPX domain limits the phosphate-uptake velocity,
      suppresses phosphate efflux and affects the regulation of the phosphate signal
      transduction pathway. Furthermore, split-ubiquitin assays and co
      immunoprecipitation suggest that the SPX domain of both Pho90 and Pho87 interacts
      physically with the regulatory protein Spl2. This work suggests that the SPX
      domain inhibits low-affinity phosphate transport through a physical interaction
      with Spl2.

PMID- 19590580
TI  - Proteome analysis of Leptospira interrogans virulent strain.
AB  - Leptospirosis is a worldwide zoonotic infection of human and veterinary concern.
      Caused by pathogenic spirochetes of the genus Leptospira, the disease presents
      greater incidence in tropical and subtropical regions. The identification of
      proteins that could be involved in the bacteria host interactions may facilitate
      the search for immune protective antigens. We report the proteomic analysis of
      Leptospira interrogans serovar Pomona virulent strain LPF cultured from kidney
      and liver of infected hamsters. Total protein extracts were separated by two
      dimensional gel electrophoresis (2-DE), 895 spots were analyzed by MALDI-TOF mass
      spectrometry (MS), and 286 were identified as leptospiral proteins, corresponding
      to 108 distinct proteins. These proteins are allocated in all the bacterial cell
      compartments and are distributed in every functional category. Furthermore, the
      previously described, known outer membrane proteins, OmpL1, LipL21, LipL31,
      LipL32/Hap-1, LipL41, LipL45, LipL46, LruA/LipL71, and OmpA-like protein Loa22
      were all recognized. Most importantly, this research work identified 27 novel
      leptospiral proteins annotated as hypothetical open reading frames (ORFs). We
      report for the first time an array of proteins of the Leptospira expressed by
      virulent, low-passage strain. We believe that our studies, together with the
      genome data will enlighten our understanding of the disease.

PMID- 19590581
TI  - The Hepatitis C Virus NS5A Stimulates NS5B During In Vitro RNA Synthesis in a
      Template Specific Manner.
AB  - The hepatitis C virus (HCV) NS5B protein contains the RNA dependent RNA
      polymerase (RdRp) activity that catalyzes the synthesis of the viral genome with
      other host and viral factors. NS5A is an HCV-encoded protein previously shown to
      localize to the replisome and be necessary for viral replication. However, its
      role in replication has not been defined. Using an in vitro biochemical assay, we
      detected a stimulatory effect of NS5A on the NS5B replication reaction with
      minimal natural templates. NS5A stimulates replication by NS5B on two templates
      derived from the 3' end of the RNA genome (4 fold +/- 1.3 fold). A pre-incubation
      step with the two proteins prior to the replication reaction and
      substoichiometric levels of NS5A are required for detecting stimulation. With a
      template derived from the 3'end complementary to the RNA genome (the negative
      strand) no stimulation was observed. Furthermore, with a synthetic template that
      allows studying different phases of replication, NS5A stimulates NS5B during
      elongation. These findings suggest that NS5A stimulates NS5B during synthesis of
      the complementary (i.e., negative) strand of the RNA genome.

PMID- 19590587
TI  - Histopathologic changes of the radial artery wall secondary to transradial
      catheterization.
AB  - OBJECTIVE: The immediate effects of transradial access on the radial artery wall
      are unknown. In this study we sought to assess the histological changes induced
      by catheterization on the radial artery. METHODS: Thirty-four patients undergoing
      coronary artery bypass grafting (CABG) had radial arteries harvested to serve as
      bypass conduits. The proximal and distal ends of the radial artery conduits were
      sectioned and embedded in paraffin. Both ends of all specimens were evaluated by
      a blinded pathologist for intimal hyperplasia, medial inflammation, medial
      calcification, periarterial tissue or fat necrosis, adventitial inflammation,
      adventitial necrosis, and adventitial neovascularization. Fisher's exact test was
      used for statistical analysis. RESULTS: Fifteen previously catheterized radial
      arteries (TRA group) were compared with 19 noncatheterized arteries (NCA group).
      The distal ends of the TRA group showed significantly more intimal hyperplasia
      (73.3% vs 21.1%; p = 0.03), periarterial tissue or fat necrosis (26% vs 0%; p =
      0.02), and more adventitial inflammation (33.3% vs 0%; p = 0.01) than the distal
      ends of the NCA group. The distal ends of the TRA group also showed significantly
      more intimal hyperplasia (73.3% vs 26.6%; p = 0.03) and adventitial inflammation
      (33.3% vs 0%; p = 0.01) than the proximal ends of the same arteries. There were
      no histological differences in the proximal ends of the two groups. CONCLUSION:
      Transradial catheterization induces significant histological changes suggestive
      of radial artery injury limited to the puncture site in the form of intimal
      hyperplasia, medial inflammation, and tissue necrosis. Both the proximal and
      distal ends of the radial artery show a spectrum of atherosclerotic changes
      independent of its use for transradial catheterization.

PMID- 19590589
TI  - The role of insulin detemir in overweight type 2 diabetes management.
AB  - The recent evidence-based shift towards an algorithm of early initiation and
      aggressive titration of insulin therapy in the management of type 2 diabetes
      requires the use of an effective insulin formulation that is both safe and
      acceptable to patients and physicians alike. The advent of the long-acting
      insulin analogues, insulin detemir and glargine, in the last decade has
      revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic
      and pharmacodynamic properties have offered tangible advantage over the
      conventional intermediate and long-acting insulin preparations in terms of
      improving glucose control as well as reducing risk of hypoglycemia and weight
      gain. This review focuses on the pharmacodynamic properties of the long-acting
      insulin analogue detemir, the outcome of studies on its relative efficacy and
      safety as well as its proposed place in the management of type 2 diabetes.

PMID- 19590591
TI  - Retrieved Unicompartmental Implants with Full PE Tibial Components: The Effects
      of Knee Alignment and Polyethylene Thickness on Creep and Wear.
AB  - Creep and true wear of polyethylene are difficult to evaluate on radiographs of
      knee arthroplasties and for this reason the true rate of polyethylene wear in
      vivo after unicompartmental arthroplasty is not well known. This study evaluated
      the creep and true wear in fifty-five medial retrieved unicompartmental implants
      that had a flat articular surface at the time of implantation.All the full
      polyethylene tibial components had the same design and were retrieved from eleven
      to 224 months (mean 152 months) after their implantation. The postoperative varus
      deformity had been measured on weight-bearing radiographs of the whole limb (hip
      knee-ankle angle). The retrieved implants were placed in a coordinate measuring
      machine and the coordinates of a grid of points were obtained. Using this system,
      a three dimensional scaled image of the implant could be created and was used to
      calculate the total penetration of the femoral condyle due to true wear and
      creep.Total linear penetration rates ranged from 0.18 to 2.6 millimeters per year
      (mean 0.25 millimeters per year). Linear penetration rates due to true wear
      ranged from 0.08 to 1.4 millimeters per year (mean 0.13 millimeter per year), and
      penetration due to creep ranged from 0.07 to 1.9 millimeters per year (mean 0.12
      millimeters per year).The linear and volumetric penetration rates of the femoral
      condyle due to true wear were negatively correlated with the duration of
      implantation. The linear penetration rate due to creep was higher in the first
      two years after the implantation compared to the subsequent years. Using multiple
      linear regression analyses to remove the confounding effects of age, weight,
      gender and thickness of the implant, we found that an increase of the
      postoperative varus deformity was due to an increase of creep (p = 0.03) but not
      with an increase of true wear (p = 0.25). Thinner implants were due to an
      increase of creep (p = 0.02) but not with an increase of true wear (p = 0.34).
      Increase in age was in relation with decrease of wear (p = 0.02) and increase of
      weight with increase in creep (p = 0.03).Plastic deformation had a high influence
      on the penetration rate of the femoral condyle in full polyethylene implants.
      There is a risk of an increased penetration and a decrease of the remaining
      thickness of the tibial plateau when the implant is too thin, the knee mal
      aligned and the patient heavy - each of these factors increasing the creep
      deformation. In conclusion, our study suggests that surgeons using the Lotus Mk I
      unicompartmental knee replacement for medial tibiofemoral arthritis should beware
      of the overweight patient (>90kg) with a tibial implant of less than 9 mm. There
      is a risk of increased penetration and decreased thickness of the tibial implant
      when it is too thin, the knee malaligned, and the patient heavy. All these
      factors increase creep deformation.

PMID- 19590590
TI  - Anteroposterior diameter of the infrarenal abdominal aorta is higher in women
      with polycystic ovary syndrome.
AB  - BACKGROUND: Women affected by polycystic ovary syndrome (PCOS) are known to be at
      higher risk of cardiovascular disease. The aim of this study was to identify the
      artery that first is affected by early pre-atherosclerotic changes in PCOS.
      METHODS: Twenty-nine women with PCOS aged 17 to 27 years and 26 healthy
      nonhyperandrogenic volunteers with regular menses (control women) aged 16 to 28
      years were enrolled. All PCOS patients were overweight or obese (body mass index
      [BMI] > or = 25). Diagnosis of PCOS was performed in line with the 2003 Rotterdam
      ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Accordingly, PCOS was defined
      when at least two of the following three features were present after exclusion of
      other etiologies: 1) oligomenorrhea and or anovulation; 2) hyperandrogenism
      and/or hyperandrogenemia; and 3) polycystic ovaries visible at ultrasound.
      Androgen excess or related disorders were excluded. The intima-media thickness
      (IMT) of common carotid arteries and common femoral arteries and the
      anteroposterior diameter of the infrarenal abdominal aorta were measured by
      ultrasound. Lutenizing hormone (LH), follicle-stimulating hormone (FSH),
      estradiol, total testosterone, androstenedione, and sex hormone-binding globulin
      (SHBG) serum levels were measured between the 3rd and the 6th day of spontaneous
      or progestin-induced menstrual cycle. Our study was performed in the absence of
      any medical treatment. RESULTS: Women with PCOS showed a higher LH to FSH ratio
      (p < 0.01), increased fasting insulin (p < 0.001), total testosterone (p <
      0.001), and androstenedione (p < 0.001) levels, and lower SHBG concentrations (p
      < 0.001) compared to control women. BMI and waist-to-hip ratio were also higher
      in women with PCOS (p < 0.000 and p < 0.001, respectively). Women with PCOS also
      showed increased total cholesterol (p < 0.001), triglyceride (p < 0.001), and
      apolipoprotein B (p < 0.001) levels. Vascular data showed women with PCOS had a
      higher anteroposterior diameter than control women (p < 0.005). However, when
      analysis of covariance was performed and BMI was entered into the model as a
      covariate, anteroposterior diameter did not maintain a significant association
      with PCOS. CONCLUSION: This study shows that anteroposterior diameter of the
      infrarenal abdominal aorta, but not IMT of common carotid arteries or common
      femoral arteries, is higher in women with PCOS than in women without this
      disease. This represents the earliest atherosclerotic change in women with PCOS.
      However, this alteration seems to be due to body weight secondary to PCOS and not
      due to PCOS per se.

PMID- 19590588
TI  - Pleiotropic effects of statins in atrial fibrillation patients: the evidence.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice. The understanding of the pathophysiology of AF has changed during the
      last several decades, and a significant role of inflammation and of the renin
      angiotensin-aldosterone system has been postulated both experimentally and
      clinically. There is emerging evidence of an association between inflammation and
      AF, and mounting evidence links increased C-reactive protein levels not only to
      already existing AF but also to the risk of developing future AF. The beneficial
      effects of statins on AF have been reported in several studies. Several
      randomized clinical and large observational studies have shown similar result
      that show the beneficial effect of statins in AF. In clinical studies, statins
      were considered effective in preventing AF after electrical cardioversion, post
      ablation, and after permanent pacemaker and implantable cardioverter
      defibrillator insertion. The antiarrhythmic mechanisms of statins regarding AF
      prevention in patients with heart failure are still not clear. Perioperative
      statin use has been associated with favorable postoperative outcome in both
      cardiovascular and noncardiovascular conditions. Despite a growing body of
      evidence that drugs with anti-inflammatory properties such as statins may prevent
      AF, the observed positive effects of statins on the burden of AF appeared to be
      independent of their cholesterol-reducing properties. However, further data from
      large-scale randomized trials are clearly needed.

PMID- 19590592
TI  - The Nature of Increased Circulating CD4CD25Foxp3 T Cells in Patients with
      Systemic Lupus Erythematosus: A Novel Hypothesis.
AB  - The forkhead family transcriptional factor (Foxp3) is an important lineage marker
      for regulatory T (Treg) cells. Foxp3 expression is primarily restricted to
      CD4+CD25+ cell population. Recently, an intriguing phenomenon is highlighted that
      there is a considerable amount of CD4(+)CD25(-)Foxp3(+) T cells present in the
      peripheral blood of patients with systemic lupus erythematosus (SLE). Up to now,
      it is still an open question as to the nature of this cell subset. Following an
      analyses of the available phenotypic characteristics of CD4(+)CD25(-)Foxp3(+) T
      cell subset along with some new findings in research of Treg in human SLE, we
      propose the hypothesis: the increased circulating CD4(+)CD25(-)Foxp3(+) T cells
      in patients with SLE may constitute a peripheral reservoir of CD4(+)CD25(+)
      Foxp3(+) Treg cells. Under the condition of autoimmune response reactivated,
      CD4(+)CD25(-)Foxp3(+) T cells could be recruited to expand the Treg pool upon
      CD25 regaining, for the effort to try to reverse a homeostatic imbalance shift to
      more aggressive expansion of autoreactive T cells and B cells. This hypothesis,
      if confirmed, would provide a new strategy for the treatment of SLE via the
      generation of therapeutic regulatory T cells.

PMID- 19590593
TI  - Effect of hemodialysis, coronary artery disease and diabetes on cardiac troponin
      T: a prospective survey over one year.
AB  - BACKGROUND: Limited data is available about the effects of hemodialysis sessions,
      coronary artery disease (CAD), and diabetes on serum cardiac troponin T (cTnT)
      levels in patients with end-stage renal disease (ESRD). OBJECTIVES: To test
      whether hemodialysis could be associated with an increase in cTnT concentration.
      To evaluate if coronary artery disease (CAD) or diabetes are associated with
      higher cTnT levels in ESRD. METHODS: Serum cTnT levels were measured immediately
      before and after dialysis 3 times over 1 year (0, 6, and 12 months). RESULTS: A
      total of 100 ESRD patients without acute coronary syndrome (mean age of 58.5
      years, 34% with diabetes, and 37% with CAD) gave 267 pre-dialysis and 260 post
      dialysis blood samples. The mean (standard deviation) pre-dialysis cTnT levels
      were 0.06 (0.12), 0.05 (0.06), and 0.07 (0.07) mcg/L at 0, 6, and 12 months,
      respectively. The post-dialysis cTnT levels were similar on average. Among 259
      samples with cTnT measured both before and after dialysis, 79 (30.5%) showed a
      decrease in serum cTnT, 97 (37.5%) showed an increase and 83 (32%) showed no
      change following dialysis. Mean cTnT was higher in CAD than in non-CAD patients.
      We observed no significant difference in mean cTnT levels between diabetic and
      non-diabetic patients. CONCLUSIONS: cTnT levels were not affected by individual
      hemodialysis sessions, and remained stable around 0.06 mcg/L over a 1-year period
      in ESRD patients. Random cTnT levels were higher in stable CAD patients
      undergoing hemodialysis.

PMID- 19590595
TI  - A new method for isolating host-independent variants of Bdellovibrio
      bacteriovorus using E. coli auxotrophs.
AB  - Bdellovibrios are Gram-negative bacteria that are characterized by predatory
      behavior. Although Bdellovibrios exhibit an obligatory parasitic life cycle, it
      is possible to isolate Bdellovibrio variants that no longer require host cells
      for their growth. In this study, a new method for isolating Bdellovibrio
      bacteriovorus host-independent (HI) variants was developed. Filtered B.
      bacteriovorus prey cells were cultured with E. coli diaminopimelic acid (DAP)
      auxotrophs as host cells. Thereafter, the lysate was plated on DAP minus media,
      allowing only HI colonies to develop. Using this method, we have isolated
      numerous HI variants and demonstrated that the emergence of HI variants may be
      occurring at a higher frequency than was previously suggested.

PMID- 19590594
TI  - Effectiveness of rituximab in severe Wegener's granulomatosis: report of two
      cases and review of the literature.
AB  - We hereby describe the satisfactory evolution of rituximab treatment in two
      patients with Wegener's granulomatosis (WG). Rituximab was indicated for
      refractoriness to standard treatment in one case and life-threatening
      myelotoxicity due to alkylating agents in the other. A brief review of previous
      experience with the use of rituximab in the treatment of WG is presented.

PMID- 19590596
TI  - Efficacy of acupuncture for the treatment of fibromyalgia: systematic review and
      meta-analysis of randomized trials.
AB  - OBJECTIVE: The study sought to ascertain the effectiveness of acupuncture as a
      treatment for fibromyalgia MATERIALS AND METHODS: THE FOLLOWING ELECTRONIC
      DATABASES WERE SEARCHED: PubMed; The Cochrane Library (CENTRAL); EMBASE; CINAHL;
      and Pascal Biomed (last date of search: January 2008). We analyzed pain intensity
      and patient withdrawals prior to termination of the study. A meta-analysis was
      performed, and a weighted global effect obtained using the inverse of variance.
      RESULTS: This review covered a total of 6 studies (323 subjects). No
      statistically significant differences were observed in terms of pain intensity
      (VAS): 0.02 (-0.24 a 0.28) or withdrawals: RR 0.91 (0.53 a 1.58) CONCLUSION: This
      systematic review found no evidence of benefit resulting from acupuncture versus
      placebo, as a treatment for fibromyalgia.

PMID- 19590598
TI  - PPARs: A Double-Edged Sword in Cancer Therapy?

PMID- 19590597
TI  - Sequestration of Alkyltin(IV) compounds in aqueous solution: formation,
      stability, and empirical relationships for the binding of dimethyltin(IV) cation
      by N- and O-donor ligands.
AB  - The sequestering ability of polyamines and aminoacids of biological and
      environmental relevance (namely, ethylenediamine, putrescine, spermine, a
      polyallylamine, a branched polyethyleneimine, aspartate, glycinate, lysinate)
      toward dimethyltin(IV) cation was evaluated. The stability of various
      dimethyltin(IV) / ligand species was determined in NaCl(aq) at t = 25 degrees C
      and at different ionic strengths (0.1 <or= I/mol L(-1) <or= 1.0), and the
      dependence of stability constants on this parameter was modeled by an Extended
      Debye-Huckel equation and by Specific ion Interaction Theory (SIT) approach. At I
      = 0.1 mol L(-1), for the ML species we have log K = 10.8, 14.2, 12.0, 14.7, 11.9,
      7.7, 13.7, and 8.0 for ethylenediamine, putrescine, polyallylamine, spermine,
      polyethyleneimine, glycinate, lysinate, and aspartate, respectively. The
      sequestering ability toward dimethyltin(IV) cation was defined by calculating the
      parameter pL(50) (the total ligand concentration, as -log C(L), able to bind 50%
      of metal cation), able to give an objective representation of this ability.
      Equations were formulated to model the dependence of pL(50) on different
      variables, such as ionic strength and pH, and other empirical predictive
      relationships were also found.

PMID- 19590609
TI  - Towards integrated primary health care for depressive disorder in the
      Netherlands. The depression initiative.

PMID- 19590611
TI  - Health and social services: living together apart.

PMID- 19590610
TI  - Quality improvement in depression care in the Netherlands: the Depression
      Breakthrough Collaborative. A quality improvement report.
AB  - BACKGROUND: Improving the healthcare for patients with depression is a priority
      health policy across the world. Roughly, two major problems can be identified in
      daily practice: (1) the content of care is often not completely consistent with
      recommendations in guidelines and (2) the organization of care is not always
      integrated and delivered by multidisciplinary teams. AIM: To describe the content
      and preliminary results of a quality improvement project in primary care, aiming
      at improving the uptake of clinical depression guidelines in daily practice as
      well as the collaboration between different mental health professionals. METHOD:
      A Depression Breakthrough Collaborative was initiated from December 2006 until
      March 2008. The activities included the development and implementation of a
      stepped care depression model, a care pathway with two levels of treatment
      intensity: a first step treatment level for patients with non-severe depression
      (brief or mild depressive symptoms) and a second step level for patients with
      severe depression. Twelve months data were measured by the teams in terms of one
      outcome and several process indicators. Qualitative data were gathered by the
      national project team with a semi-structured questionnaire amongst the local team
      coordinators. RESULTS: Thirteen multidisciplinary teams participated in the
      project. In total 101 health professionals were involved, and 536 patients were
      diagnosed. Overall 356 patients (66%) were considered non-severely depressed and
      180 (34%) patients showed severe symptoms. The mean percentage of non-severe
      patients treated according to the stepped care model was 78%, and 57% for the
      severely depressed patient group. The proportion of non-severely depressed
      patients receiving a first step treatment according to the stepped care model,
      improved during the project, this was not the case for the severely depressed
      patients. The teams were able to monitor depression symptoms to a reasonable
      extent during a period of 6 months. Within 3 months, 28% of monitored patients
      had recovered, meaning a Beck Depression Inventory (BDI) score of 10 and lower,
      and another 27% recovered between 3 and 6 months. CONCLUSIONS AND DISCUSSION: A
      stepped care approach seems acceptable and feasible in primary care, introducing
      different levels of care for different patient groups. Future implementation
      projects should pay special attention to the quality of care for severely
      depressed patients. Although the Depression Breakthrough Collaborative introduced
      new treatment concepts in primary and specialty care, the change capacity of the
      method remains unclear. Thorough data gathering is needed to judge the real value
      of these intensive improvement projects.

PMID- 19590612
TI  - Integrated primary health care: Finnish solutions and experiences.
AB  - BACKGROUND: Finland has since 1972 had a primary health care system based on
      health centres run and funded by the local public authorities called
      'municipalities'. On the world map of primary health care systems, the Finnish
      solution claims to be the most health centre oriented and also the widest, both
      in terms of the numbers of staff and also of different professions employed.
      Offering integrated care through multi-professional health centres has been
      overshadowed by exceptional difficulties in guaranteeing a reasonable access to
      the population at times when they need primary medical or dental services.
      Solutions to the problems of access have been found, but they do not seem
      durable. DESCRIPTION OF POLICY PRACTICE: During the past 10 years, the health
      centres have become a ground of active development structural change, for which
      no end is in sight. Broader issues of municipal and public administration
      structures are being solved through rearranging primary health services. In these
      rearrangements, integration with specialist services and with social services
      together with mergers of health centres and municipalities are occurring at an
      accelerated pace. This leads into fundamental questions of the benefits of
      integration, especially if extensive integration leads into the threat of the
      loss of identity for primary health care. DISCUSSION: This article ends with some
      lessons to be learned from the situation in Finland for other countries.

PMID- 19590613
TI  - Quantitative Doppler-echocardiographic determination of regurgitant volume in
      patients with aortic insufficiency.
AB  - BACKGROUND: The severity of aortic regurgitation (AR) can be determined by
      invasive or echocardiographic methods. We systematically compared quantitative
      invasive and echocardiographic data with semiquantitative invasive grades in a
      prospective series of patients. METHODS: Using Doppler-echocardiography we
      determined the cardiac output over the aortic, pulmonary and mitral valve in 27
      patients (20 with, 7 without AR). Aortic regurgitant volume was calculated as the
      difference between the cardiac output over aortic and pulmonary valve/ mitral
      valve. During angiography the severity of AR was assessed semiquantitatively by
      aortography and the regurgitant volume was calculated invasively as the
      difference between the left- and right ventricular cardiac output. RESULTS: The
      echocardiographically and invasively determined regurgitant blood volume
      correlated closely (R approximately 0.8). The regurgitant volume increased with
      higher angiographic grade but there was significant overlap between adjoining
      qualitative grades. CONCLUSION: In patients with AR, quantitative
      echocardiographic and angiographic measurements of the regurgitant volume
      correlate closely.

PMID- 19590614
TI  - Oral giant cell granuloma in a patient with glycogen storage disease.
AB  - The glycogen storage disease (GSD) is a group of inherited disorders that involve
      deficiencies in the enzymes that metabolize glycogen. The purpose of the present
      paper is to report a rare case of GSD type 1b that presented both peripheral and
      central giant cell granuloma, and to discuss the possible explanation for this
      unusual finding. The use of corticosteroids in the management of central giant
      cell granuloma is also demonstrated.

PMID- 19590615
TI  - Total Dislocation of the Talus without a Fracture. Open or Closed Treatment?
      Report of Two Cases and Review of the Literature.
AB  - Complete dislocation of the talus not accompanied by a fracture is a very rare
      injury. The injury is encountered as a closed one even more rarely. Reviewing the
      literature we found that proposed treatments for total talus dislocation varied
      from primary talectomy or arthodesis (to avoid complications) to closed reduction
      and an under knee cast. Most importantly, there was no agreement among authors
      about the method of reduction (open/closed). We report our experience with two
      cases of closed total talus dislocation not accompanied by a fracture, and review
      the literature to retrieve evidence on whether a closed or open treatment should
      be preferred for this type of injury.

PMID- 19590617
TI  - Is progress by selection, really progress?

PMID- 19590618
TI  - The current role of PET-CT in the characterization of hepatobiliary malignancies.
AB  - BACKGROUND: Surgery has become heavily dependent on accurate imaging in the
      assessment and treatment of suspected or confirmed intra-abdominal malignancy.
      Positron emission tomography-computed tomography (PET-CT) fuses uptake of a
      radiotracer combined with CT images to assess both functional tissue activity and
      anatomical detail. Since its introduction it has offered new ways of treating
      gastrointestinal cancers. METHODS: The review analyses the present literature
      regarding the use of PET-CT in the assessment, diagnosis, staging and treatment
      of hepatobiliary malignancies. RESULTS: PET-CT is widely used in pre-operative
      tumours staging for colorectal liver metastases. There is convincing data that it
      may also be applicable for neuroendocrine tumours, assessment of indeterminate
      pancreas lesions and clinical drug trials. PET-CT is of limited value in
      hepatocellular cancers, although new techniques in dual-tracer PET-CT may change
      this. CONCLUSION: Knowledge of the strengths and limitations of PET-CT is
      important for all surgeons managing cancer of the hepatobiliary system. More
      clinical data are required on PET-CT, particularly its effect on long-term
      survival in PET-CT-staged patients undergoing resection.

PMID- 19590619
TI  - Impact of margin status on survival following pancreatoduodenectomy for cancer:
      the Leeds Pathology Protocol (LEEPP).
AB  - BACKGROUND: In a previous study we reported an 85% R1 rate for pancreatic cancer
      following the use of the rigorous, fully standardized Leeds Pathology Protocol
      (LEEPP). As this significantly exceeded R1 rates observed by others, we
      investigated the reproducibility of margin assessment using the LEEPP in a
      larger, prospective, observational cohort study and correlated
      clinicopathological data with survival. METHODS: Clinicopathological features,
      including exact site and multifocality of margin involvement, and survival were
      collated from a prospective series of 83 pancreatoduodenectomies for pancreatic
      (n = 27), ampullary (n = 24) and bile duct cancer (n = 32). Data were compared
      with those of the previous study in which the same pathology protocol, based on
      axial slicing and extensive tissue sampling from the circumferential margin, had
      been used. RESULTS: The R1 rate was high in pancreatic (82%) and bile duct (72%)
      cancer and significantly lower in ampullary cancer (25%). Margin positivity was
      often multifocal, the posterior margin being most frequently involved. Margin
      status correlated with survival in the entire cohort (P = 0.006) and the
      pancreatic subgroup (P = 0.046). These findings were consistent with observations
      in our previous study. CONCLUSIONS: Margin involvement in pancreatic cancer is a
      frequent and prognostically significant finding when specimens are assessed using
      the LEEPP.

PMID- 19590620
TI  - The effect of mesh reinforcement of a stapled transection line on the rate of
      pancreatic occlusion failure after distal pancreatectomy: review of a single
      institution's experience.
AB  - BACKGROUND: Pancreatic occlusion failure (POF) after distal pancreatectomy
      remains a common source of morbidity. Here, we review our experience with distal
      pancreatectomy and attempt to identify factors which influence POF rates.
      PATIENTS AND METHODS: One hundred sixty-nine distal pancreatectomies were
      performed between 2002 and 2007. Review of the computerized medical records and
      physician office records was performed for all patients. Univariate and
      multivariate analyses were performed to determine factors which might influence
      the incidence of POF. The data set was analysed for factors which might influence
      the pancreatic occlusion rate. Analysis included patient and disease
      characteristics including: age, gender, body mass index (BMI), diagnosis,
      consistency of the pancreas and history of pancreatitis, as well as intra
      operative variables including: surgeon, absorbable mesh reinforcement and
      operative approach. RESULTS: POF was the most common peri-operative complication.
      POF was identified in 32 out of 169 patients (19%). Transection technique (hand
      sewn, stapled, stapled with mesh) and procedure complexity were factors
      associated with differences in POF rates by both univariate and multivariate
      analyses. POF was identified in 7 out of 70 patients (10%) when an absorbable
      mesh was utilized, and 25 of 99 patients (25%) when mesh was not utilized (P <
      0.02). DISCUSSION: These data suggest that a randomized controlled trial will be
      required to determine if mesh reinforcement reduces the rate and severity of POF
      after distal pancreatectomy.

PMID- 19590621
TI  - Timing of referral impacts surgical outcomes in patients undergoing repair of
      bile duct injuries.
AB  - Bile duct injury (BDI) after laparoscopic cholecystectomy (LC) remains a
      significant surgical challenge. Despite claims to the contrary, the incidence of
      bile duct injury has remained elevated since the introduction of LC. Several
      issues regarding the surgical management of BDI are controversial, including: (i)
      identification of the surgeon and centre most capable of managing the injury,
      (ii) timing of surgical repair, (iii) incidence and significance of associated
      vascular injury and (iv) identification of patient factors which significantly
      impact outcome after repair. Variability in timing of referral of BDI to tertiary
      centres has been noted in the literature. The impact of timing of referral upon
      post-operative outcomes after definitive surgery has yet to be clearly
      investigated. We report our experience with 44 patients who required
      reconstructive surgery after BDI. In contrast to the many studies available in
      the literature, patients in the current study were classified according to a
      modern injury classification system. Additionally, we examined the impact of
      delayed referral to our centre on short- and long-term outcomes after surgical
      repair of BDI.

PMID- 19590622
TI  - Hepatic parenchyma resection using stapling devices: peri-operative and long-term
      outcome.
AB  - BACKGROUND: Stapler-assisted hepatectomy has not been well established, as a
      routine procedure, although few reports exist in the literature. This analysis
      assesses the safety and outcome of the method based on peri-operative data.
      MATERIALS AND METHODS: From February 2005 to December 2006, endo GIA vascular
      staplers were used for parenchymal liver transection in 62 consecutive cases in
      our department. There were 18 (29%) patients with hepatocellular carcinoma (HCC),
      31 (50%) with metastatic lesions and 13 (21%) with benign lesions [adenoma, focal
      nodular hyperplasia (FNH), simple cysts]. Twenty-one patients underwent major
      resections (33.9%) (i.e. removal of three segments or more) and 41 (66.1%) minor
      hepatic resections. RESULTS: Median blood loss was 260 ml. The median total
      operative time was 150 min and median transection time was 35 min. No patient
      required more than 2 days of intensive care unit (ICU) treatment. The median
      hospital stay was 8 days. Surgical complications included two (3%) cases of bile
      leak, two (3%) cases of pneumonia, two (3%) cases with wound infection and two
      (3%) cases with pleural effusion. The peri-operative mortality was zero. In a 30
      month median follow-up, all patients with benign lesions were alive and free of
      disease. The 3-year disease-free survival for patients with HCC was 61% (57% for
      patients with colorectal metastases) and the 3-year survival 72% (68% for
      patients with colorectal metastases). CONCLUSION: Stapler-assisted liver
      resection is feasible with a low incidence of surgical complications. It can be
      used as an alternative for parenchyma transection especially in demanding
      hepatectomies for elimination of the operating time and control of bleeding.

PMID- 19590623
TI  - Angiotensin-converting enzyme gene DD genotype neither increases susceptibility
      to acute pancreatitis nor influences disease severity.
AB  - BACKGROUND: The renin-angiotensin system (RAS) has been implied in the
      pathogenesis of various diseases including acute and chronic pancreatitis.
      Angiotensin-converting enzyme (ACE) is the key enzyme in activating the RAS.
      Deletion (D)-type polymorphism in the 16th intron of the ACE gene has been
      associated with higher serum levels of the enzyme. Inhibition of ACE was found to
      ameliorate acute pancreatitis in animal models suggesting that ACE plays a role
      in pathogenesis and progression of acute pancreatitis. Objectives were to
      investigate the occurrence of the ACE insertion/deletion (I/D) polymorphism in
      acute pancreatitis patients and its association with the severity of the disease.
      MATERIAL AND METHODS: Seventy-nine acute pancreatitis patients and 95 healthy
      controls were evaluated. Acute pancreatitis cases were grouped as mild or severe
      according to the Atlanta criteria. MAIN OUTCOME MEASURE: The presence of the ACE
      I/D polymorphism. RESULTS: ACE gene I and D allele frequency of patients (44% and
      56%) were similar to controls (45% and 55%, respectively). There were no
      significant differences in severity of pancreatitis between patients with the ACE
      insertion or ACE-insertion/deletion versus ACE-deletion genotypes. CONCLUSIONS:
      The ACE gene deletion polymorphism is neither a risk factor for development of
      acute pancreatitis nor contributes to the severity of disease or development of
      complications.

PMID- 19590624
TI  - Non-operative management of blunt liver trauma: feasible and safe also in centres
      with a low trauma incidence.
AB  - BACKGROUND AND AIMS: Non-operative management (NOM) of blunt liver trauma is
      currently, if possible, the preferred treatment of choice. The present study
      evaluates the experience of blunt liver injury in adults in a Swedish university
      hospital. MATERIAL AND METHODS: Forty-six patients with blunt liver trauma were
      treated from January 1994 through to December 2004. Patient charts were reviewed
      retrospectively to examine injury severity score (ISS), liver injury grade,
      diagnostics, treatment and outcome. RESULTS: Thirty-five patients (76%) were
      initially treated non-operatively and 11 (24%) patients had immediate surgery. In
      four (11%) patients, NOM failed and the patients required surgery 8-72 h after
      admission. Patients failing non-operative care had a significantly lower systolic
      blood pressure on admission as compared with patients with successful NOM (P =
      0.001). Patients immediately operated upon had higher ISS (P < 0.001) and were
      haemodynamically unstable to a greater extent (P < 0.001) as compared with
      patients initially considered for NOM. Operated patients had increased
      transfusion requirements (P < 0.001), longer total hospital stay (P = 0.011) and
      stay in the intensive care unit (ICU) unit (P < 0.001) as compared with NOM. One
      immediately operated and one failed NOM died (total mortality 4%). Seventeen
      patients in the NOM group were successfully treated without surgery despite the
      presence of at least one described risk factor. CONCLUSIONS: Most patients with
      blunt liver trauma can be treated without surgery, and non-operative management
      may be performed even in the presence of established risk factors.

PMID- 19590625
TI  - Outcomes in pancreatic resection are negatively influenced by pre-operative
      hospitalization.
AB  - BACKGROUND: Quality improvement in high-acuity surgery increasingly relies on
      clinical pathways to streamline patient care and to maximize cost-efficiency.
      Yet, it remains unclear whether immediate pre-operative hospitalization (non
      elective resection) influences operative performance and to what extent it alters
      the post-operative course. METHODS: Retrospective case series, cost
      analysis.University tertiary care referral centre. Four hundred and twelve
      consecutive pancreatic resections performed for benign and malignant disease
      between 2001 and 2008. Outcomes for both elective and non-elective operations
      were scrutinized, and correlated with deviations from our clinical Carepath for
      Pancreatic Resection. Observed-to-expected (O/E) morbidity ratios were calculated
      for each. RESULTS: Overall, 39 patients (10%) required immediate pre-operative
      hospitalization, 22 (56%) of which were transferred from another hospital. The
      most common indications were pancreatitis, gastric outlet obstruction,
      intractable abdominal pain and gastrointestinal bleeding. During a 1- to 2-week
      hospitalization, 51% of patients underwent endoscopic retrograde cholangio
      pancreatography (ERCP), 36% were administered parenteral nutrition, 20% received
      antibiotics and 15% were transfused blood products. Yet, this pre-operative
      scenario, at a median cost of $7250 per patient, had no measurable impact on
      operative performance. Post-operatively, non-elective patients suffered more
      complications and a higher (O/E) ratio (1.00 vs. 0.93). These outcomes resulted
      in significantly more deviations from our carepath and an additional $7000 per
      non-elective case. CONCLUSION: Immediate pre-operative hospitalization has no
      meaningful impact on operative performance; yet, deviations from a standardized
      clinical pathway are far more likely after non-elective pancreatic resection, and
      result in more severe clinical and economic outcomes.

PMID- 19590626
TI  - Altered aquaporin 9 expression and localization in human hepatocellular
      carcinoma.
AB  - BACKGROUND: In addition to the biochemical components secreted in bile, aquaporin
      (AQP) water channels exist in hepatocyte membranes to form conduits for water
      movement between the sinusoid and the bile canaliculus. The aim of the current
      study was to analyse AQP 9 expression and localization in human hepatocellular
      carcinoma (HCC) and non-tumourigenic liver (NTL) tissue from patients undergoing
      hepatic resection. METHODS: Archived tissue from 17 patients was sectioned and
      analysis performed using an antibody raised against AQP 9. Slides were blind
      scored to determine AQP 9 distribution within HCC and NTL tissue. RESULTS:
      Aquaporin 9 was predominantly expressed in the membranes of hepatocytes and
      demonstrated zonal distribution relative to hepatic sinusoid structure in normal
      liver. In HCC arising in the absence of cirrhosis AQP 9 remained membrane
      localized with zonal distribution in the majority of NTL. By contrast, AQP 9
      expression was significantly decreased in the HCC mass vs. pair-matched NTL. In
      HCC in the presence of cirrhosis, NTL was characterized by extensive AQP 9
      staining in the membrane in the absence of zonal distribution and AQP 9 staining
      in NTL was significantly greater than that observed in the tumour mass.
      CONCLUSIONS: These data demonstrate that human HCC is characterized by altered
      AQP 9 expression and AQP 9 localization in the NTL mass is dependent on
      underlying liver pathology. Given the central role of AQPs in normal liver
      function and the potential role of AQPs during transformation and progression,
      these data may prove valuable in future diagnostic and/or therapeutic strategies.

PMID- 19590627
TI  - Outcome of surgical treatment for recurrent pyogenic cholangitis: a single-centre
      study.
AB  - BACKGROUND: Recurrent pyogenic cholangitis (RPC) is still a common disease in
      East Asia. The present study reviews the operative results for this disease in a
      single centre. METHODS: The records of 85 patients who underwent surgical
      treatment for RPC from August 1995 to March 2008 were retrospectively reviewed.
      RESULTS: Patients included 35 men and 50 women with a median age of 61 years.
      Types of surgery included: hepatectomy (65.9%); hepatectomy plus drainage (9.4%);
      drainage alone (14.1%), and percutaneous choledochoscopy (10.6%). There was no
      operative mortality. Complications occurred in 40% of patients and half the
      complications involved wound infections. The overall incidences of residual
      stone, stone recurrence and biliary sepsis recurrence were 21.2%, 16.5% and
      21.2%, respectively, over a median follow-up of 45.4 months. The drainage-alone
      group and percutaneous choledochoscopy group had higher incidences of residual
      stone, stone recurrence and biliary sepsis recurrence. In hepatectomy patients,
      regardless of whether or not a drainage procedure had been performed, rates of
      residual stone, stone recurrence and biliary sepsis recurrence were 15.6%, 7.8%
      and 9.4%, respectively, over a median follow-up of 42.7 months. CONCLUSIONS:
      Hepatectomy is safe and yields the best treatment outcome for RPC. It should be
      considered as the treatment of choice for suitable patients with RPC.

PMID- 19590628
TI  - Poorer survival in patients whose explanted hepatocellular carcinoma (HCC)
      exceeds Milan or UCSF Criteria. An analysis of liver transplantation in HCC in
      Australia and New Zealand.
AB  - BACKGROUND: Milan and University of California San Francisco (UCSF) Criteria have
      been used for selection of patients with hepatocellular carcinoma (HCC) for liver
      transplantation (LTx). The aims of this study were to analyse the results of LTx
      for HCC in Australia and New Zealand with emphasis on the effects of discordance
      between pre-LTx radiological and post-LTx pathological staging. METHODS: A total
      of 186 LTx for HCC carried out between July 1985 and August 2003 were included.
      Patients were categorized according to the Milan and UCSF Criteria. RESULTS: The
      median follow-up was 6.55 years (range 2.96-20.93 years). Pre-LTx factors
      associated with better survival include tumour size < or = 5 cm, number of
      tumours < or = 3, staging within Milan and UCSF Criteria and more recent
      transplantation (1996-2003). In all, 14 patients had a pre-LTx stage outside the
      Milan but within the UCSF Criteria. One- and 5-year patient survival rates were,
      respectively, 88% and 74% within the Milan Criteria, and 87% and 73% within the
      UCSF Criteria. Vascular invasion, capsular invasion, lymph node invasion and
      pathological stage outside UCSF Criteria were associated with poor outcome. Of
      patients within the Milan and UCSF Criteria pre-LTx, 24% and 18%, respectively,
      were outside the same criteria post-LTx. These patients had poorer survival
      rates. CONCLUSIONS: The use of the UCSF Criteria in this cohort increased the
      number of patients eligible for LTx without compromising 5-year survival rates.
      Patients whose explant tumours were outside the Milan or UCSF Criteria had poorer
      outcomes compared with those whose explants remained within these criteria.

PMID- 19590629
TI  - Use of staplers to divide the pancreas during pancreatoduodenectomy: is it
      justified?

PMID- 19590630
TI  - Can we apply the process improvement tool Six Sigma to enhance outcomes in
      hepatopancreatobiliary surgery?

PMID- 19590631
TI  - Current status of minimally invasive necrosectomy for post-inflammatory
      pancreatic necrosis.
AB  - OBJECTIVE: This paper reviews current knowledge on minimally invasive pancreatic
      necrosectomy. BACKGROUND: Blunt (non-anatomical) debridement of necrotic tissue
      at laparotomy is the standard method of treatment of infected post-inflammatory
      pancreatic necrosis. Recognition that laparotomy may add to morbidity by
      increasing postoperative organ dysfunction has led to the development of
      alternative, minimally invasive methods for debridement. This study reports the
      status of minimally invasive necrosectomy by different approaches. METHODS:
      Searches of MEDLINE and EMBASE for the period 1996-2008 were undertaken. Only
      studies with original data and information on outcome were included. This
      produced a final population of 28 studies reporting on 344 patients undergoing
      minimally invasive necrosectomy, with a median (range) number of patients per
      study of nine (1-53). Procedures were categorized as retroperitoneal, endoscopic
      or laparoscopic. RESULTS: A total of 141 patients underwent retroperitoneal
      necrosectomy, of whom 58 (41%) had complications and 18 (13%) required
      laparotomy. There were 22 (16%) deaths. Overall, 157 patients underwent
      endoscopic necrosectomy; major complications were reported in 31 (20%) and death
      in seven (5%). Laparoscopic necrosectomy was carried out in 46 patients, of whom
      five (11%) required laparotomy and three (7%) died. CONCLUSIONS: Minimally
      invasive necrosectomy is technically feasible and a body of evidence now suggests
      that acceptable outcomes can be achieved. There are no comparisons of results,
      either with open surgery or among different minimally invasive techniques.

PMID- 19590632
TI  - Hypertrophy of the non-embolized liver after chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NC(+)) and portal vein embolization (PVE)
      enables curative resection in more patients with colorectal-liver metastases
      (CRLM). However, after NC(+), structural alterations have been reported with the
      risk of post-operative hepatic failure. We undertook to determine if NC(+)
      toxicity limits future remnant liver (FRL) hypertrophy after PVE. METHODS: PVE
      was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI
      (5-fluorouracil + leucovorin + irinotecan) regimen (NC(+)) of 6.6 cycles. The
      seven remaining patients served as the control group without NC (NC(-)). RESULTS:
      CRLM were bilateral in 69% (NC(+)) and 57% (NC(-)), and synchronous in 84%
      (NC(+)) and 14% (NC(-)). The FRL hypertrophy rate was 54.1% (NC(+)) and 43.7%
      (NC(-)) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group
      NC(+): one insufficient FRL hypertrophy and one severe steatosis; and group NC(
      ): two tumoral progressions. In both groups, the operative parameters were
      comparable except for pedicular clamping: 8 (NC(+)) and 36 min (NC(-)),
      respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were
      comparable. No significant pathological difference was observed between the two
      groups. No mortality occurred in either group. CONCLUSION: In view of our limited
      experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not
      altered after FOLFIRI-based NC.

PMID- 19590633
TI  - Effect of remote ischemic preconditioning on hepatic microcirculation and
      function in a rat model of hepatic ischemia reperfusion injury.
AB  - BACKGROUND: Liver transplantation involves a period of ischemia and reperfusion
      to the graft which leads to primary non-function and dysfunction of the liver in
      5-10% of cases. Remote ischemic preconditioning (RIPC) has been shown to reduce
      ischemia reperfusion injury (IRI) injury to the liver and increase hepatic blood
      flow. We hypothesized that RIPC may directly modulate hepatic microcirculation
      and have investigated this using intravital microscopy. METHODS: A rat model of
      liver IRI was used with 45 min of partial hepatic ischemia (70%) followed by 3 h
      of reperfusion. Four groups of animals (Sham, IRI, RIPC+IRI, RIPC+Sham) were
      studied (n= 6, each group). Intravital microscopy was used to measure red blood
      cell (RBC) velocity, sinusoidal perfusion, sinusoidal flow and sinusoidal
      diameter. Neutrophil adhesion was assessed by rhodamine labeling of neutrophils
      and cell death using propidium iodide. RESULTS: RIPC reduced the effects of IRI
      by significantly increasing red blood cell velocity, sinusoidal flow and
      sinusoidal perfusion along with decreased neutrophil adhesion and cell death.
      CONCLUSIONS: Using intravital microscopy, this study demonstrates that RIPC
      modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a
      key role in the modulation of hepatic microcirculation and endothelial function.

PMID- 19590634
TI  - Surgical bypass vs. endoscopic stenting for pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The majority of patients with pancreatic cancer are non-resectable
      and jaundiced at presentation. Methods of palliation in such patients with
      locally advanced disease comprise endoscopic placement of a biliary
      endoprosthesis or surgical bypass. METHODS: This retrospective study compared
      morbidity, mortality, hospital stay, readmission rate and survival in consecutive
      patients with incurable locally advanced pancreatic ductal adenocarcinoma.
      RESULTS: We identified a total of 56 patients, of whom 33 underwent endoscopic
      stenting and 23 underwent a surgical bypass consisting of a hepaticojejunostomy
      en-Y and a gastrojejunostomy. There were no significant differences in
      complication or mortality rates between patients undergoing palliative stenting
      and those undergoing palliative surgery. However, after excluding admissions for
      chemotherapy-related problems, the number of readmissions expressed as a
      percentage of the group population size was greater in stented patients compared
      with biliary bypass patients (39.4% vs. 13.0%, respectively; P < 0.05). Overall
      survival amongst patients undergoing palliative bypass was significantly greater
      than in stented patients (382 days vs. 135 days, respectively; P < 0.05).
      CONCLUSIONS: On analysis of these data and the published literature, we conclude
      that surgical bypass represents an effective method of palliation for patients
      with locally advanced pancreatic cancer. Patients need to be carefully selected
      with regard to both operative risk and perceived overall survival.

PMID- 19590635
TI  - Surgical management of patients with post-cholecystectomy benign biliary
      stricture complicated by atrophy-hypertrophy complex of the liver.
AB  - BACKGROUND: Atrophy-hypertrophy complex (AHC) of the liver rarely complicates
      post-cholecystectomy benign biliary strictures (BBS). This study aimed to analyse
      the effect of AHC on the surgical management of patients with BBS. METHODS:
      Between 1989 and 2005, 362 patients underwent surgical repair for BBS at a
      tertiary referral centre in northern India. A total of 36 (10%) patients had AHC.
      Patients with AHC (n= 36) were compared with those without (n= 336) to define the
      factors associated with the development of AHC. RESULTS: Overall, 35 patients
      with AHC underwent Roux-en-Y hepaticojejunostomy; right hepatectomy was performed
      in one patient. The interval between bile duct injury and stricture repair did
      not influence the development of AHC (mean 24 months in AHC patients vs. 19
      months in non-AHC patients; P= 0.522). Of the 36 patients with AHC, 26 (72%) had
      hilar strictures (Bismuth's types III, IV, V), as did 163 of the 326 (50%)
      patients without AHC (P= 0.012). Patients with AHC had more blood loss at surgery
      (mean blood loss 340 ml in the AHC group vs. 190 ml in the non-AHC group; P=
      0.004) and required more blood transfusion (mean blood transfused 300 ml vs. 120
      ml; P= 0.001). Surgery was prolonged in AHC patients (mean duration of operation
      4.2 hours in the AHC group vs. 2.8 hours in the non-AHC group; P= 0.001). Over a
      mean follow-up of 43 months (range 6-163 months), three of 36 (8%) AHC patients
      required re-intervention for recurrent strictures, compared with nine of 326 (3%)
      non-AHC patients (P= 0.006). CONCLUSIONS: Iatrogenic injury at the hepatic hilum
      predisposes for the development of AHC. Surgery is more difficult and blood
      transfusion requirements are higher in patients with AHC during surgical repair
      of BBS. Atrophy-hypertrophy complex is a risk factor for recurrent stricture
      formation after hepaticojejunostomy.

PMID- 19590636
TI  - Medicolegal costs of bile duct injuries incurred during laparoscopic
      cholecystectomy.
AB  - BACKGROUND: When laparoscopic cholecystectomy (LC) is performed successfully,
      recovery is faster than after open cholecystectomy. However, LC results in higher
      incidences of biliary, bowel and vascular injury. METHODS: We performed a
      retrospective review of LC-related claims reported to the National Health Service
      Litigation Authority (NHSLA) during 2000-2005. The data were analysed from a
      medicolegal perspective to assess the effects of type of injury and delay in
      recognition on litigation costs. RESULTS: A total of 208 claims following
      laparoscopic procedures in general surgery were reported to NHSLA during 2000
      2005, of which 133 (64%) were related to LC. Bile duct injury (BDI) accounted for
      the majority of claims (72%); bowel injury and 'others' accounted for 9% and 19%,
      respectively. Only 20% of BDIs were recognized during surgery; the majority were
      missed and diagnosed later. Claims related to LC resulted in payments totalling 6
      m pound sterling, of which 4.3 m pound sterling was paid out for BDIs. The
      average cost was higher for patients who suffered a delay in diagnosis, as was
      the chance of a successful claim. CONCLUSIONS: Bile duct injury incurred during
      LC remains a serious hazard for patients. The resulting complications have led to
      litigation that has caused a huge financial drain on the health care system.
      Delayed recognition appears to correlate with more costly litigation.

PMID- 19590637
TI  - Novel laparoscopic bipolar radiofrequency energy technology for expedited hepatic
      tumour ablation.
AB  - BACKGROUND: Monopolar radiofrequency ablation (RFA) is a well accepted modality
      for local control of hepatic tumours, but its effectiveness is challenged by
      prolonged ablation time, an inconsistent ablation zone and susceptibility to
      energy loss from convective heat loss from adjacent high-velocity blood flows
      ('heat sinks'). Bipolar RFA employs a dual parallel electrode array; the energy
      wave travels unidirectionally between and not around electrodes. This 'line-of
      sight' delivery streams energy between two fixed points and concentrates energy
      delivery to the area between the probes. Bipolar RFA is postulated to yield
      reduced ablation time and to reduce or eliminate convective heat loss from
      adjacent high-velocity blood flows. The current study evaluated the feasibility,
      time and safety of this novel FDA-approved bipolar RFA technology using a
      laparoscopic approach in human liver tumours. METHODS: Using the prospectively
      maintained surgical oncology hepatic-pancreatic-biliary database, 17 consecutive
      patients (26 liver tumours) who underwent laparoscopic bipolar ablations were
      reviewed. Electrodes were placed using guidance by intraoperative ultrasound and
      trajectory planning needles. Ablation time was recorded and postoperative
      computed tomography scans were obtained. RESULTS: A total of 18 lesions (in 12
      patients) represented metastatic colorectal cancer. Three lesions (in two
      patients) were hepatocellular carcinoma. Four lesions (in two patients)
      represented locally advanced symptomatic gallbladder cancer invading the liver
      bed or symptomatic intrahepatic liver metastases from gallbladder cancer. One
      lesion was benign hepatic adenoma. Mean tumour size was 3.07 +/- 1.42 cm. Mean
      ablation time was 358 +/- 120 sec. No major complications were observed in the <
      or = 30-day or >30-day periods post-RFA. CONCLUSIONS: Laparoscopic bipolar RFA is
      a quick, safe technique which adds a new tool to our armamentarium for treating
      hepatic tumours. Establishing its longterm oncological outcome will require
      longer follow-up and the exact role of this technique in the current
      multimodality management remains to be defined.

PMID- 19590638
TI  - The effect of a multimodal fast-track programme on outcomes in laparoscopic liver
      surgery: a multicentre pilot study.
AB  - OBJECTIVES: This study was conducted to evaluate the added value of an enhanced
      recovery after surgery (ERAS) programme in laparoscopic liver resections for
      solid tumours. METHODS: Patients undergoing laparoscopic liver resection between
      July 2005 and July 2008 were included. Indications for resections included
      presumed benign and malignant liver lesions. Primary outcome was total length of
      hospital stay (LOS). Secondary outcomes were functional recovery, complications,
      conversions, blood loss and duration of operation. RESULTS: Thirteen patients
      were treated by laparoscopic liver resections in the ERAS programme in one centre
      (group 1). Their outcomes were compared with outcomes of 13 laparoscopic
      procedures performed either before the introduction of the ERAS programme during
      2003-2005 in the same centre or during the same period in other centres using
      traditional care (group 2). Median total LOS was 5.0 days (range 3-10 days) in
      group 1 and 7.0 days (3-12 days) in group 2. This difference was not
      statistically significant. Functional recovery occurred 2 days earlier in group 1
      (median 3.0 days [range 1-7 days] vs. median 5.0 days [range 2-8 days]; P <
      0.044). There were no significant differences in complications, conversions or
      duration of operation. Blood loss was significantly less in the ERAS group
      (median 50 ml [range 50-200 ml] vs. median 250 ml [range 50-800 ml]; P < 0.002).
      CONCLUSIONS: This exploratory, multicentre, fast-track laparoscopic liver
      resection study is the first such study conducted. Although small, the study
      suggests that a multimodal enhanced recovery programme in laparoscopic liver
      surgery is feasible, safe and may lead to accelerated functional recovery and
      reductions in LOS.

PMID- 19590639
TI  - Evaluation of a bipolar radiofrequency device for laparoscopic hepatic resection:
      technique and clinical experience in 18 patients.
AB  - BACKGROUND: The increased frequency of laparoscopic hepatic resection as a
      principal or adjunct component of patient care has driven the need for and
      development of efficient and safe hepatic parenchymal transection technologies.
      At present, various devices are available for pre-coagulation transection (PCT)
      of hepatic parenchyma with the intent of minimizing procedure-associated
      postoperative haemorrhage and bile leak. This report presents the evaluation of a
      novel bipolar radiofrequency (RF) energy device for PCT used for laparoscopic
      hepatic resection. METHODS: Patients undergoing laparoscopic hepatic resection
      using the Enseal device (SurgRx Inc.) were identified from the prospectively
      maintained hepatobiliary database. Information on patient demographics,
      procedures and postoperative complications was collected and analysed;
      complications were grouped into early (at <30 days) and late (at > or = 30 days)
      events. RESULTS: A total of 18 patients, of whom 13 had malignant tumours (12
      colorectal metastases and one hepatocellular carcinoma) and five had benign
      tumours (two hepatic adenomas and three haemangiomas) underwent 18 hepatic
      procedures, including two formal hemi-hepatectomies, four left lateral sections,
      three posterior sections and nine atypical non-anatomic resections. Estimated
      blood loss did not differ from institutional historical control data; no
      postoperative haemorrhage, bile leaks or hepatic abscess or necrosis were
      identified (n = 18). CONCLUSIONS: This initial experience using the laparoscopic
      bipolar RF device demonstrates an acceptable safety profile in terms of the
      outcomes analysed.

PMID- 19590640
TI  - Refining indications for contemporary surgical treatment of renal cell carcinoma
      metastatic to the pancreas.
AB  - BACKGROUND: The pancreas is a rare location for metastatic disease, with only 2
      11% of all pancreatic tumours being of non-primary origin. It is also uncommon
      for renal cell carcinoma (RCC) to metastasize to the pancreas (1-3% of cases)
      and, when it does, it typically occurs substantially after index nephrectomy. It
      is not known whether all pancreatic metastases need be resected because today's
      chemo- and biological therapies are increasingly effective in controlling
      advanced disease. METHODS: Six patients with a variety of symptoms are discussed.
      Four patients presented with recurrent gastrointestinal bleeding, ranging from
      occult to life-threatening in severity. RESULTS: The four patients with
      gastrointestinal bleeding had RCC metastases that had eroded into the duodenum
      and were successfully controlled by palliative pancreaticoduodenectomy or
      completion pancreatectomy. The other two patients were treated using different
      chemotherapeutic or biological agents. CONCLUSIONS: Renal cell carcinoma
      metastases to the pancreas typically occur long after index nephrectomy. Although
      clinical presentation is variable, palliative resection should be reserved for
      those who develop complications, such as upper gastrointestinal bleeding, and, in
      other series, obstructive jaundice. Routine debulking resections do not appear to
      be indicated because current biological therapies effectively and reliably
      control disease over long periods.

PMID- 19590641
TI  - Modified Cattell's pancreaticojejunostomy, buttressing for soft pancreases and an
      isolated biliopancreatic loop are safety measurements that improve outcome after
      pancreaticoduodenectomy: a pilot study.
AB  - BACKGROUND: Pancreatic anastomotic leak is one of the most serious complications
      following pancreaticoduodenectomy (PD). Various factors have been implicated as
      contributors to pancreatic anastomotic leaks, the incidence of which has been as
      high as 28% in some series. OBJECTIVES: We describe technical modifications to
      Cattell's technique for pancreaticojejunostomy (PJ), with buttressing of 'soft'
      pancreases and use of an isolated biliopancreatic loop for reconstruction
      following a PD. METHODS: We report our early experience using this technique in
      50 patients who underwent PD between May 2002 and June 2006. RESULTS: There was
      no mortality in our series. The postoperative morbidity rate was 32% (16/50),
      with major complications occurring in seven (14%) patients. Pancreatic leak
      occurred in one patient (2%) and bile leak in one patient (2%). Both patients
      were managed conservatively. CONCLUSIONS: Reconstruction after PD using an
      isolated biliopancreatic loop and modifications to Cattell's technique for PJ,
      with buttressing of the soft pancreas, can be performed with a low risk of
      pancreatic anastomotic leakage.

PMID- 19590642
TI  - Aberrant right hepatic arterial anatomy and pancreaticoduodenectomy: recognition,
      prevalence and management.
AB  - BACKGROUND: Aberrant arterial anatomy is a common finding during foregut surgery.
      Anomalies to the right hepatic lobe are especially relevant during
      pancreaticoduodenectomy (PD) and their recognition serves to protect the blood
      supply to the liver and bile ducts. We report our experience with aberrant right
      hepatic arterial anatomy (ARHAA) found during PD. METHODS: All patients who
      underwent PD between February 2003 and June 2007 were retrospectively reviewed
      and those with ARHAA were identified. Preoperative imaging studies were assessed
      by one radiologist, graded according to the presence of ARHAA and compared with
      the original interpretations. RESULTS: We found ARHAA in 31 of 191 patients
      (16.2%). Operative management included dissection and preservation in 24,
      transection and reconstruction in four, and transection and primary anastomosis
      in three patients. Reconstruction of ARHAA was carried out through interposition
      grafts in two patients and implantation into the gastroduodenal stump in two
      patients. No cases of arterial thrombosis, liver infarction, abscess formation or
      biliary fistula were demonstrated in the immediate postoperative period. Review
      of preoperative imaging interpretations found that only nine of 23 reports
      indicated the presence of ARHAA; however, the retrospective review of the images
      found that ARHAA was readily apparent in 24 patients. DISCUSSION: Recognition of
      aberrant vasculature to the liver before PD is important. Preoperative imaging
      studies will often be adequate to identify these anomalies, but interpreting
      radiologists may not be aware of its clinical significance. Surgeons performing
      PD must be adept at managing ARHAA safely.

PMID- 19590643
TI  - Incidence of individual organ dysfunction in fatal acute pancreatitis: analysis
      of 1024 death records.
AB  - BACKGROUND: Extrapancreatic organ dysfunction is the key determinant of mortality
      in acute pancreatitis (AP). This study aimed to document the frequency and
      duration of individual organ dysfunction in all fatalities caused by AP in a
      large, population-based cohort. METHODS: All deaths caused by AP in Scotland
      between 2000 and 2006 inclusive were analysed (n = 1024). RESULTS: The median
      time lapse between the onset of AP and death was 6 days (interquartile range
      [IQR] 17 days); that between the onset of organ dysfunction and death was 3 days
      (IQR 7 days). There was no apparent bimodal distribution. The majority of
      patients had single- (384 patients) or two-system (242 patients) extrapancreatic
      organ dysfunction. Pulmonary dysfunction was most prevalent (30% of organ
      specific entries, 198/660), followed by cardiovascular (18%, 117/660), renal
      (16%, 108/660), liver (11%, 71/660), gastrointestinal (9%, 59/660), haemorrhage
      (6%, 38/660), coagulopathy (5%, 31/660) and central nervous system (6%, 38/660)
      dysfunction. CONCLUSIONS: Death in AP occurs early in the disease course. The
      present findings support the primacy of pulmonary injury as the modal pattern of
      organ dysfunction in severe AP, with increased frequencies of cardiovascular and
      renal compromise in fatal AP.

PMID- 19590644
TI  - Endoscopic treatment of persistent thoracobiliary fistulae after penetrating
      liver trauma.
AB  - BACKGROUND: This study evaluated the outcomes of patients with complex or
      persistent thoracobiliary fistulae following penetrating liver trauma, who
      underwent endoscopic biliary intervention at a tertiary referral centre. METHODS:
      All patients who underwent endoscopic retrograde cholangiography (ERC) and
      endoscopic biliary intervention for traumatic thoracobiliary fistulae between
      1992 and 2008 were evaluated. Bile duct injuries were classified according to
      their biliary anatomic location on cholangiography and type of pulmonary
      communication. RESULTS: Twenty-two patients had thoracobiliary (pleurobiliary, n
      = 19; bronchobiliary, n = 3) fistulae. The site of the bile duct injury was
      identified in 20 patients on cholangiography. These 20 patients underwent either
      sphincterotomy and biliary stenting (n = 18) or sphincterotomy alone (n = 2). In
      17 patients the fistulae resolved after the initial endoscopic intervention.
      Three patients required secondary stenting with replacement of the initial stent.
      Three patients developed mild pancreatitis after stenting and one stent migrated
      and was replaced. All fistulae healed after endoscopic treatment. In 18 patients
      the stents were removed 4 weeks after bile drainage ceased. Three of the 22
      patients required a thoracotomy for infected loculated pleural collections after
      initial catheter drainage. CONCLUSIONS: Endoscopic retrograde cholangiography is
      an accurate and reliable method of demonstrating post-traumatic thoracobiliary
      fistulae and endoscopic biliary intervention with sphincterotomy and stenting in
      this situation is safe and effective. Surgery in patients with thoracobiliary
      fistulae should be reserved for fistulae which do not heal after endoscopic
      biliary stenting or for patients who have unresolved pulmonary or intra-abdominal
      sepsis as a result of bile leak.

PMID- 19590645
TI  - Biliary access in technically difficult biliary cannulation: the mucosal bridge
      technique.
AB  - BACKGROUND: The use of precut sphincterotomy during endoscopic retrograde
      cholangiopancreatography (ERCP) facilitates selective bile duct access in
      difficult procedures. However, it is also associated with high rates of
      complications. Several techniques for precut sphincterotomy have been described
      in the literature. This paper reports our experience with a non-needle-knife
      technique for precut sphincterotomy, namely, the mucosal bridge technique.
      METHODS: We analysed the experience of a single surgical endoscopist at our
      centre in performing precut sphincterotomies by retrospectively examining
      information in the database for January 2002 to February 2008, which had been
      stored prospectively using Endoscribe. RESULTS: The mucosal bridge technique was
      performed in 16 (3.19%) of 501 patients. Success rates were 75% and 100% after
      first and second ERCPs, respectively. The failure of initial procedures was
      caused by bleeding, tissue oedema, poorly visualized papilla or a poorly
      distensible duodenum and oedematous papilla. There were four cases of
      complications, which included periductular extravasation of contrast, bleeding,
      and sepsis in two patients. However, these complications were not a direct
      consequence of the precut sphincterotomy. CONCLUSIONS: The mucosal bridge
      technique can be used to increase the likelihood of successful bile duct
      cannulation, thus preventing the need for a second intervention.

PMID- 19590646
TI  - Systematic review of cholecystostomy as a treatment option in acute
      cholecystitis.
AB  - OBJECTIVES: Percutaneous cholecystostomy (PC) is an established low-mortality
      treatment option for elderly and critically ill patients with acute
      cholecystitis. The primary aim of this review is to find out if there is any
      evidence in the literature to recommend PC rather than cholecystectomy for acute
      cholecystitis in the elderly population. METHODS: In April 2007, a systematic
      electronic database search was performed on the subject of PC and cholecystectomy
      in the elderly population. After exclusions, 53 studies remained, comprising 1918
      patients. Three papers described randomized controlled trials (RCTs), but none
      compared the outcomes of PC and cholecystectomy. A total of 19 papers on
      mortality after cholecystectomy in patients aged >65 years were identified.
      RESULTS: Successful intervention was seen in 85.6% of patients with acute
      cholecystitis. A total of 40% of patients treated with PC were later
      cholecystectomized, with a mortality rate of 1.96%. Procedure mortality was
      0.36%, but 30-day mortality rates were 15.4 % in patients treated with PC and
      4.5% in those treated with acute cholecystectomy (P < 0.001). CONCLUSIONS: There
      are no controlled studies evaluating the outcome of PC vs. cholecystectomy and
      the papers reviewed are of evidence grade C. It is not possible to make
      definitive recommendations regarding treatment by PC or cholecystectomy in
      elderly or critically ill patients with acute cholecystitis. Low mortality rates
      after cholecystectomy in elderly patients with acute cholecystitis have been
      reported in recent years and therefore we believe it is time to launch an RCT to
      address this issue.

PMID- 19590647
TI  - Surgical management of hepatolithiasis.
AB  - BACKGROUND: Globalization and intercontinental migration have not just changed
      the socioeconomic status of regions, but have also altered disease dynamics
      across the globe. Hepatolithiasis, although still rare, is becoming increasingly
      evident in the West because of immigration from the Asia-Pacific region, where
      the disease prevails in endemic proportions. Such rare but emerging diseases pose
      a therapeutic challenge to doctors. METHODS: Here, we briefly introduce the topic
      of hepatolithiasis and describe features of intrahepatic stones, the aetiology of
      hepatolithiasis and the symptoms and sequelae of the condition. We then provide a
      comprehensive review of the various management modalities currently in use to
      treat hepatolithiasis. CONCLUSIONS: In our opinion, and as is evident from the
      literature, surgery remains the definitive treatment for hepatolithiasis.
      However, non-surgical procedures such as cholangiography, although limited in
      their therapeutic capabilities, play a vital role in diagnosis and preoperative
      evaluation.

PMID- 19590648
TI  - Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of
      choice.
AB  - BACKGROUND: A pancreatic fistula (PF) is the most common complication after
      pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%.
      The aim of the present study was to analyse the treatment of a complicated PF
      comparing the surgical approach with conservative techniques. METHODS: From
      January 2000 through to August 2006, 121 patients were submitted for PD. The
      study consisted of 70 men and 47 women, with a median age of 60 years (SD +/-
      12). The main indications for PD were pancreatic duct carcinoma in 52 patients
      (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11
      (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients
      (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS: Thirty-five
      patients (30%) developed a PF. Amongst these, 20 were managed conservatively and
      14 were reoperated. These two groups of patients were compared with patients
      without a PF for analysis. There was no significant difference in the mean age,
      the gender ratio, American Society of Anesthesiologists (ASA) classification,
      surgical time and blood replacement, number of associated procedures, vascular
      resection and type of reconstruction between the three groups. There were five
      post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment
      group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of
      hospital stay (P < 0.001) were greater in the surgical group. The medium delay
      between the pancreatic resection and reoperation was 10 days (range, 3-32 days).
      Completion splenopancreatectomy was required in five patients whereas
      conservative treatment including debridement and drainage was applied in nine
      patients. CONCLUSION: The surgical approach for a PF is associated with a higher
      mortality and morbidity. There is no advantage in performing completion
      pancreatectomy (CP) instead of extensive drainage as a result of the same
      mortality and morbidity rates and the risk of endocrine insufficiency. In cases
      of complicated PF, radiological or surgical conservative treatment is
      recommended.

PMID- 19590649
TI  - Distal pancreatectomy: what is the standard for laparoscopic surgery?
AB  - BACKGROUND/AIMS: Distal pancreatectomy (DP) is performed for a range of benign
      and malignant lesions. Accurate pre-operative diagnosis can be unreliable and
      morbidity remains high. This study evaluates a 12-year, single-centre experience
      with open DP to review indications, diagnoses and associated morbidity. METHODS:
      Retrospective review of patients who underwent DP at a UK-based tertiary referral
      centre between 1994 and 2006. RESULTS: Sixty-five patients (mean age 49.9 years)
      had final diagnoses of chronic pancreatitis +/- pseudocyst (n= 22), benign
      cystadenoma (n= 15), neuroendocrine tumour (n= 8), primary pancreatic carcinoma
      (n= 6) and 14 other conditions. DP performed for presumed cystic neoplasm (n= 24)
      revealed a correct pre-operative diagnosis in 71% of patients. Histological
      examination confirmed that 59% of resected cystic tumours were either malignant
      or had malignant potential. When DP was undertaken for presumed pseudocyst (n=
      12), 83% of cases were correctly diagnosed pre-operatively. Overall mortality and
      morbidity rates were 3% and 39%, respectively, with five patients (8%) developing
      a clinically significant pancreatic fistula. Ten (17%) patients developed
      diabetes mellitus and nine (14%) required long-term pancreatic exocrine
      supplementation. CONCLUSIONS: Open DP can be performed with acceptable morbidity,
      low mortality and preservation of pancreatic function in the majority of cases,
      setting the standard for laparoscopic techniques.

PMID- 19590651
TI  - Risk of pancreatitis after endoscopic retrograde cholangiopancreatography and
      endoscopic biliary drainage.
AB  - BACKGROUND: Pancreatitis is the most common and serious complication to occur
      after endoscopic retrograde cholangiopancreatography (ERCP). It is often
      associated with additional diagnostic modalities and/or treatment of obstructive
      jaundice. The aim of this study was to determine the risk of post-ERCP
      pancreatitis associated with pancreaticobiliary examination and endoscopic
      biliary drainage (EBD). METHODS: A total of 740 consecutive ERCP procedures
      performed in 477 patients were analysed for the occurrence of pancreatitis. These
      included 470 EBD procedures and 167 procedures to further evaluate the
      pancreaticobiliary tract using brush cytology and/or biopsy, intraductal
      ultrasound and/or peroral cholangioscopy or peroral pancreatoscopy. The
      occurrence of post-ERCP pancreatitis was analysed retrospectively. RESULTS: The
      overall incidence of post-ERCP pancreatitis was 3.9% (29 of 740 procedures). The
      risk factors for post-ERCP pancreatitis were: being female (6.5%; odds ratio [OR]
      2.5, P= 0.02); first EBD procedure without endoscopic sphincterotomy (ES) (6.9%;
      OR 3.0, P= 0.003), and performing additional diagnostic procedures on the
      pancreatobiliary duct (9.6%; OR 4.6, P < 0.0001). Pancreatitis after subsequent
      draining procedures was rare (0.4%; OR for first-time drainage 16.6, P= 0.0003).
      Furthermore, pancreatitis was not recognized in 59 patients who underwent ES.
      Seven patients with post-EBD pancreatitis were treated with additional ES.
      CONCLUSIONS: Invasive diagnostic examinations of the pancreaticobiliary duct and
      first-time perampullary biliary drainage without ES were high-risk factors for
      post-ERCP pancreatitis. Endoscopic sphincterotomy may be of use to prevent post
      EBD pancreatitis.

PMID- 19590650
TI  - Prediction of post-operative pancreatic fistula in pancreaticoduodenectomy
      patients using pre-operative MRI: a pilot study.
AB  - BACKGROUND: Post-operative pancreatic fistula (POPF) is one of the most fearful
      complications which may occur after pancreaticoduodenectomy (PD). The methods
      used to predict POPF pre-operatively have not been studied in great detail. We
      analyzed correlation between various parameters related to PD including pre
      operative magnetic resonance imaging (MRI) signal intensity (SI), pathology of
      pancreatic fibrosis and occurrence rates of POPF, and verified that MRI SI
      results could be the determining values for pre-operative prediction of POPF.
      METHODS: From January 2005 to August 2006, we retrospectively examined 43 cases
      of PDs by reviewing abdominal MRI findings, degree of fibrosis of remnant
      pancreatic stump, and other surgery-related parameters. RESULTS: POPF encountered
      in PD were 11 cases (25.6%). Operation time and degree of fibrosis of remnant
      pancreatic cut surface were related to POPF (P= 0.030, P= 0.010). The pancreas
      liver SI ratio (PLSI) between fistula group and no fistula group was -0.0009 +/-
      0.2 and -0.1297 +/- 0.2, respectively (P= 0.0004). The pancreas-spleen SI ratio
      (PSSI) in each group was 0.423 +/- 0.25 and 0.288 +/- 0.32, respectively (P=
      0.014). Using quantitative analysis, the SI ratios were 1.27 and 0.66 in each
      group (P= 0.013). CONCLUSIONS: When analyzing the results of POPF in 43 patients
      who underwent PD, PLSI, PSSI and qualitative analysis, fistula group differed
      significantly from no fistula group. Using these results, it will be helpful for
      us to predict the occurrence of POPF pre-operatively using MRI in PD patients.

PMID- 19590652
TI  - Renal haemodynamics and function following partial portal decompression.
AB  - BACKGROUND: This study was undertaken to prospectively evaluate the impact of
      partial portal decompression on renal haemodynamics and renal function in
      patients with cirrhosis and portal hypertension. METHODS: Fifteen consecutive
      patients (median age 49 years) with cirrhosis underwent partial portal
      decompression through portacaval shunting or transjugular intrahepatic
      portosystemic shunting (TIPS). Cirrhosis was caused by alcohol in 47%, hepatitis
      C in 13%, both in 33% and autoimmune factors in 7% of patients. Child class was A
      in 13%, B in 20% and C in 67% of patients. The median score on the Model for End
      stage Liver Disease (MELD) was 14.0 (mean 15.0 +/- 7.7). Serum creatinine (SrCr)
      and creatinine clearance (CrCl) were determined pre-shunt, 5 days after shunting
      and 1 year after shunting. Colour-flow Doppler ultrasound of the renal arteries
      was also undertaken with calculation of the resistive index (RI) and pulsatility
      index (PI). Changes in the portal vein-inferior vena cava pressure gradient with
      shunting were determined. RESULTS: With shunting, the portal vein-inferior vena
      cava gradients dropped significantly, with significant increases in PI in the
      early period after shunting. Creatinine clearance improved in the early post
      shunt period. However, SrCr levels did not significantly improve. At 1 year after
      shunting, both CrCl and SrCr levels tended towards pre-shunt levels and the
      increase in PI did not persist. DISCUSSION: Partial portal decompression improves
      mild to moderate renal dysfunction in patients with cirrhosis. Early improvements
      in renal function after shunting begin to disappear by 1 year after shunting.

PMID- 19590653
TI  - Surgical management and longterm follow-up of non-parasitic hepatic cysts.
AB  - BACKGROUND: Despite the increasing use of laparoscopic techniques, the optimal
      surgical approach for cystic liver disease has not been well defined. This study
      aims to determine the optimum operative approach for these patients. METHODS:
      Data were identified from the Lothian Surgical Audit, case note review and
      general practitioner contact. Patients were contacted and asked to complete the
      SF-36 questionnaire on quality of life. RESULTS: A total of 102 patients (67 with
      simple cysts, 31 with polycystic liver disease [PCLD], four with cystic tumours)
      underwent 62 laparoscopic deroofings, 15 open deroofings, 36 resections and one
      liver transplant between June 1985 and April 2006. The median follow-up was 77
      months (range 3-250 months). Morbidity and recurrent symptom rates after
      laparoscopic surgery were greater in PCLD patients compared with simple cyst
      patients, at 31% (four patients) vs. 15% (seven patients) and 85% (11 patients)
      vs. 29% (24 patients), respectively. Four patients with simple cysts and eight
      with PCLD required further surgery. All patients with simple cysts had comparable
      quality of life after surgery. Patients with recurrent symptoms after surgery for
      PCLD had a significantly better quality of life following laparoscopic deroofing
      than after resection. CONCLUSIONS: Most simple cysts can be managed
      laparoscopically, but there is a definite role for open resection in some
      patients. Open deroofing is the preferred approach for a dominant cyst pattern in
      PCLD, whereas resection is necessary for diffuse cystic disease.

PMID- 19590654
TI  - Simultaneous pancreatectomy and liver transplantation: a single-institution
      experience.
AB  - BACKGROUND: There is wide debate among transplant centres regarding the
      indications for liver transplantation (LT) in malignancy. We report a single
      centre experience with simultaneous LT and total pancreatectomy or
      pancreaticoduodenectomy. METHODS: We performed a retrospective review of a
      prospectively established database of patients who underwent simultaneous LT and
      total pancreatectomy or pancreaticoduodenectomy. We analysed demographics,
      indications, approach and outcomes. RESULTS: Between 1991 and 2006, 11 patients
      (four male; median age 51 years) underwent simultaneous LT and total
      pancreatectomy (n = 4) or pancreaticoduodenectomy (n = 7). Indications included
      metastatic neuroendocrine tumour (n = 5), hepatocellular carcinoma (n = 2),
      metastatic periampullary adenocarcinoma (n = 1), periampullary adenocarcinoma
      with end-stage liver disease (ESLD) (n = 2) and intraductal papillary mucinous
      neoplasm with ESLD (n = 1). The three patients with ESLD had non-alcoholic
      steatohepatitis, primary sclerosing cholangitis or cryptogenic cirrhosis. Median
      postoperative length of stay was 31 days (21-110 days). Overall median survival
      was 101 months (95% confidence interval 70.6-131.4). One-year survival was 91%, 2
      year 90%, 5-year 67% and 10-year 33%. Postoperative complications included: re
      operation (n = 4); anastamotic leak (n = 2); abdominal abscess (n = 3), and organ
      rejection (n = 1). CONCLUSIONS: We report a series of pancreatectomy or
      pancreaticoduodenectomy and simultaneous LT in patients with extensive malignancy
      or impending liver failure that prevented pancreatectomy. This series provides
      evidence that combined pancreatic resection and LT can be a strategy in both
      radical resections and cases with ESLD that would otherwise preclude operative
      intervention.

PMID- 19590655
TI  - Laparoscopic hepatectomy is a safe procedure for cancer patients.
AB  - BACKGROUND: Utilizing laparoscopy for major surgeries such as hepatectomy is a
      relatively new concept. Initially, benign pathologies dominated indications for
      resection. Our experience in an Australian setting with primarily malignant
      diagnoses is described. METHODS: A review of patients' profiles, pathology,
      surgery and outcome was performed on 35 patients between December 2005 and August
      2008. Data were collected and analysed retrospectively from medical records on a
      pre-designed datasheet. RESULTS: Commonest indication for resection was
      colorectal metastasis (54%), 71% of all resections were for malignancy. Average
      operating time was 2 h 31 min (range 30 min-7 h, 15 min). Major morbidity
      consisted of one bile leak, two subphrenic abscesses and one pulmonary embolus.
      There were no deaths. Conversion to open was required in 20% and two patients
      required intra-operative blood transfusions. Average length of stay overall was
      6.1 days (range 1-27), but as low as 2 days for some left lateral
      sectionectomies. Cessation of parenteral analgesia, return to normal diet and
      full mobility were achieved on average at 2.4, 2.3 and 2.8 days. Significant post
      operative liver dysfunction was seen in two patients, which returned to normal by
      discharge. One patient died of disease progression 4 months after surgery. There
      were two involved margins in 35 patients (6%). CONCLUSIONS: Laparoscopic
      hepatectomy is a developing and safe technique in a select group of patients
      including those with malignancies, resulting in short hospital stays, rapid
      return to normal diet, full mobility and minimal morbidity with acceptable
      oncological parameters. This study is not comparative in nature, but provides
      evidence to support further investigation and establishment of this new technique
      for liver resection.

PMID- 19590656
TI  - Surgical portosystemic shunts and the Rex bypass in children: a single-centre
      experience.
AB  - OBJECTIVES: This study aimed to illustrate the indications for, and types and
      outcomes of surgical portosystemic shunt (PSS) and/or Rex bypass in a single
      centre. METHODS: Data were collected from children with a PSS and/or Rex bypass
      between 1992 and 2006 at Mount Sinai Medical Center, New York. RESULTS: Median
      age at surgery was 10.7 years (range 0.3-22.0 years). Indications included: (i)
      refractory gastrointestinal bleeding in portal hypertension associated with (a)
      compensated cirrhosis (n= 12), (b) portal vein thrombosis (n= 10), (c)
      hepatoportal sclerosis (n= 3); (ii) refractory ascites secondary to Budd-Chiari
      syndrome (n= 3), and (iii) familial hypercholesterolaemia (n= 4). There were 20
      distal splenorenal, four portacaval, three Rex bypass, two mesocaval, two
      mesoatrial and one proximal splenorenal shunts. At the last follow-up (median 2.9
      years, range 0.1-14.1 years), one shunt (Rex bypass) was thrombosed. Two patients
      had died and two had required a liver transplant. These had a patent shunt at
      last imaging prior to death or transplant. CONCLUSIONS: Portosystemic shunts and
      Rex bypass have been used to manage portal hypertension with excellent outcomes.
      In selected children with compensated liver disease, PSS may act as a bridge to
      liver transplantation or represent an attractive alternative.

PMID- 19590657
TI  - Utility of the Gyrus open forceps in hepatic parenchymal transection.
AB  - OBJECTIVE: This study aimed to evaluate if the Gyrus open forceps is a safe and
      efficient tool for hepatic parenchymal transection. BACKGROUND: Blood loss during
      hepatic transection remains a significant risk factor for morbidity and mortality
      associated with liver surgery. Various electrosurgical devices have been
      engineered to reduce blood loss. The Gyrus open forceps is a bipolar cautery
      device which has recently been introduced into hepatic surgery. METHODS: We
      conducted a single-institution, retrospective review of all liver resections
      performed from November 2005 through November 2007. Patients undergoing resection
      of at least two liver segments where the Gyrus was the primary method of
      transection were included. Patient charts were reviewed; clinicopathological data
      were collected. RESULTS: Of the 215 open liver resections performed during the
      study period, 47 patients met the inclusion criteria. Mean patient age was 61
      years; 34% were female. The majority required resection for malignant disease
      (94%); frequent indications included colorectal metastasis (66%), hepatocellular
      carcinoma (6%) and cholangiocarcinoma (4%). Right hemihepatectomy (49%), left
      hemihepatectomy (13%) and right trisectionectomy (13%) were the most frequently
      performed procedures. A total of 26 patients (55%) underwent a major ancillary
      procedure concurrently. There were no operative mortalities. Median operative
      time was 220 min (range 97-398 min). Inflow occlusion was required in nine
      patients (19%) for a median time of 12 min (range 3-30 min). Median total
      estimated blood loss was 400 ml (range 10-2000 ml) and 10 patients (21%) required
      perioperative transfusion. All patients had macroscopically negative margins.
      Median length of stay was 8 days. Two patients (4%) had clinically significant
      bile leak. The 30-day postoperative mortality was zero. CONCLUSIONS: Use of the
      Gyrus open forceps appears to be a safe and efficient manner of hepatic
      parenchymal transection which allows rapid transection with acceptable blood
      loss, a low rate of perioperative transfusion, and minimal postoperative bile
      leak.

PMID- 19590658
TI  - Bucillamine improves hepatic microcirculation and reduces hepatocellular injury
      after liver warm ischaemia-reperfusion injury.
AB  - BACKGROUND: Liver transplantation and resection surgery involve a period of
      ischaemia and reperfusion to the liver which initiates an inflammatory cascade
      resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight
      thiol antioxidant that is capable of rapidly entering cells. METHODS: The effect
      of bucillamine was studied in a rat model of liver ischaemia-reperfusion injury
      with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion.
      Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone
      (without ischaemia reperfusion). Liver injury was assessed by serum transaminases
      (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using
      intravital microscopy (IVM). RESULTS: The hepatocellular injury of I/R produced a
      markedly elevated serum AST which was reduced with bucillamine (2072.5 +/- 511.79
      vs. 932 +/- 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R
      also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 +/-
      16.86 vs. 181.11 +/- 17.59, at the end of 3 h of reperfusion) and reduced
      hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001). CONCLUSION:
      Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and
      improves parenchymal perfusion.

PMID- 19590659
TI  - EHP paper of the year, 2009.

PMID- 19590660
TI  - Key elements of effective and practical disclosure policies for health science
      journals.

PMID- 19590661
TI  - Developmental perchlorate exposure and synaptic transmission in hippocampus.

PMID- 19590664
TI  - ENDOCRINE DISRUPTORS: Estrogens in a bottle?

PMID- 19590666
TI  - HARMFUL ALGAL BLOOMS: an unexpected deep-sea diver.

PMID- 19590668
TI  - The landscape of antibiotic resistance.

PMID- 19590667
TI  - CHILDREN'S HEALTH: gene variants may predict lung health.

PMID- 19590669
TI  - Aquaculture navigates through troubled waters.

PMID- 19590670
TI  - Prenatal preview: early bisphenol a exposure may spawn late-life reproductive
      problems.

PMID- 19590671
TI  - Legacy for young men: PFAAs and human sperm.

PMID- 19590673
TI  - The price of progress: modern environmental health hazards in Africa.

PMID- 19590672
TI  - Fat chance? A high-fat diet may offset the effects of developmental
      neurotoxicity.

PMID- 19590674
TI  - U.S. Funding is insufficient to address the human health impacts of and public
      health responses to climate variability and change.
AB  - BACKGROUND: The need to identify and try to prevent adverse health impacts of
      climate change has risen to the forefront of climate change policy debates and
      become a top priority of the public health community. Given the observed and
      projected changes in climate and weather patterns, their current and anticipated
      health impacts, and the significant degree of regulatory discussion underway in
      the U.S. government, it is reasonable to determine the extent of federal
      investment in research to understand, avoid, prepare for, and respond to the
      human health impacts of climate change in the United States. OBJECTIVE: In this
      commentary we summarize the health risks of climate change in the United States
      and examine the extent of federal funding devoted to understanding, avoiding,
      preparing for, and responding to the human health risks of climate change.
      DISCUSSION: Future climate change is projected to exacerbate various current
      health problems, including heat-related mortality, diarrheal diseases, and
      diseases associated with exposure to ozone and aeroallergens. Demographic trends
      and geophysical and socioeconomic factors could increase overall vulnerability.
      Despite these risks, extramural federal funding of climate change and health
      research is estimated to be < $3 million per year. CONCLUSIONS: Given the real
      risks that climate change poses for U.S. populations, the National Institutes of
      Health, Centers for Disease Control and Prevention, U.S. Environmental Protection
      Agency, and other agencies need to have robust intramural and extramural
      programs, with funding of > $200 million annually. Oversight of the size and
      priorities of these programs could be provided by a standing committee within the
      National Academy of Sciences.

PMID- 19590675
TI  - Modern environmental health hazards: a public health issue of increasing
      significance in Africa.
AB  - OBJECTIVES: Traditional hazards such as poor sanitation currently account for
      most of Africa's environmentally related disease burden. However, with rapid
      development absent appropriate safeguards for environment and health, modern
      environmental health hazards (MEHHs) may emerge as critical contributors to the
      continent's disease burden. We review recent evidence of human exposure to and
      health effects from MEHHs, and their occurrence in environmental media and
      consumer products. Our purpose is to highlight the growing significance of these
      hazards as African countries experience urbanization, industrial growth, and
      development. DATA SOURCES: We reviewed published epidemiologic, exposure, and
      environmental studies of chemical agents such as heavy metals and pesticides.
      DATA SYNTHESIS: The body of evidence demonstrates ongoing environmental releases
      of MEHHs and human exposures sometimes at toxicologically relevant levels.
      Several sources of MEHHs in environmental media have been identified, including
      natural resource mining and processing and automobile exhaust. Biomonitoring
      studies provided direct evidence of human exposure to metals such as mercury and
      lead and pesticides such as p,p'-dichlorodiphenyltrichloroethane (DDT) and
      organophosphates. Land and water resource pollution and industrial air toxics are
      areas of significant data gaps, notwithstanding the presence of several emitting
      sources. CONCLUSION: Unmitigated MEHH releases and human exposure have
      implications for Africa's disease burden. For Africans encumbered by conditions
      such as malnutrition that impair resilience to toxicologic challenges, the burden
      may be higher. A shift in public health policy toward accommodating the emerging
      diversity in Africa's environmental health issues is necessary to successfully
      alleviate the burden of avoidable ill health and premature death for all its
      communities now and in the future.

PMID- 19590676
TI  - A review of events that expose children to elemental mercury in the United
      States.
AB  - OBJECTIVE: Concern for children exposed to elemental mercury prompted the Agency
      for Toxic Substances and Disease Registry and the Centers for Disease Control and
      Prevention to review the sources of elemental mercury exposures in children,
      describe the location and proportion of children affected, and make
      recommendations on how to prevent these exposures. In this review, we excluded
      mercury exposures from coal-burning facilities, dental amalgams, fish
      consumption, medical waste incinerators, or thimerosal-containing vaccines. DATA
      SOURCES: We reviewed federal, state, and regional programs with information on
      mercury releases along with published reports of children exposed to elemental
      mercury in the United States. We selected all mercury-related events that were
      documented to expose (or potentially expose) children. We then explored event
      characteristics (i.e., the exposure source, location). DATA SYNTHESIS: Primary
      exposure locations were at home, at school, and at other locations such as
      industrial property not adequately remediated or medical facilities. Exposure to
      small spills from broken thermometers was the most common scenario; however,
      reports of such exposures are declining. DISCUSSION AND CONCLUSIONS: Childhood
      exposures to elemental mercury often result from inappropriate handling or
      cleanup of spilled mercury. The information reviewed suggests that most releases
      do not lead to demonstrable harm if the exposure period is short and the mercury
      is properly cleaned up. RECOMMENDATIONS: Primary prevention should include health
      education and policy initiatives. For larger spills, better coordination among
      existing surveillance systems would assist in understanding the risk factors and
      in developing effective prevention efforts.

PMID- 19590677
TI  - Prenatal exposure to bisphenol a at environmentally relevant doses adversely
      affects the murine female reproductive tract later in life.
AB  - BACKGROUND: Exposure to endocrine-disrupting chemicals during critical
      developmental periods causes adverse consequences later in life; an example is
      prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A
      (BPA), an environmental estrogen used in the synthesis of plastics, is of concern
      because its chemical structure resembles that of DES, and it is a "high-volume
      production" chemical with widespread human exposure. OBJECTIVES: In this study we
      investigated whether prenatal BPA causes long-term adverse effects in female
      reproductive tissues in an experimental animal model previously shown useful in
      studying effects of prenatal DES. METHODS: Timed pregnant CD-1 mice were treated
      on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After
      delivery, pups were held for 18 months; reproductive tissues were then evaluated.
      RESULTS: Ovarian cysts were significantly increased in the 1-mug/kg BPA group;
      ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in
      corn-oil controls. We observed increased progressive proliferative lesions of the
      oviduct after BPA treatment, similar to those described in response to DES.
      Further, although not statistically different from the controls, prominent
      mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as
      vaginal adenosis, were present in BPA-treated mice, similar to lesions reported
      following DES treatment. More severe pathologies observed in some BPA-treated
      animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma
      of the uterine cervix; and mammary adenocarcinoma. We did not observe these
      lesions in controls. CONCLUSIONS: These data suggest that BPA causes long-term
      adverse reproductive and carcinogenic effects if exposure occurs during critical
      periods of differentiation.

PMID- 19590678
TI  - Estimating regional spatial and temporal variability of PM(2.5) concentrations
      using satellite data, meteorology, and land use information.
AB  - BACKGROUND: Studies of chronic health effects due to exposures to particulate
      matter with aerodynamic diameters <or= 2.5 microm (PM(2.5)) are often limited by
      sparse measurements. Satellite aerosol remote sensing data may be used to extend
      PM(2.5) ground networks to cover a much larger area. OBJECTIVES: In this study we
      examined the benefits of using aerosol optical depth (AOD) retrieved by the
      Geostationary Operational Environmental Satellite (GOES) in conjunction with land
      use and meteorologic information to estimate ground-level PM(2.5) concentrations.
      METHODS: We developed a two-stage generalized additive model (GAM) for U.S.
      Environmental Protection Agency PM(2.5) concentrations in a domain centered in
      Massachusetts. The AOD model represents conditions when AOD retrieval is
      successful; the non-AOD model represents conditions when AOD is missing in the
      domain. RESULTS: The AOD model has a higher predicting power judged by adjusted
      R(2) (0.79) than does the non-AOD model (0.48). The predicted PM(2.5)
      concentrations by the AOD model are, on average, 0.8-0.9 microg/m(3) higher than
      the non-AOD model predictions, with a more smooth spatial distribution, higher
      concentrations in rural areas, and the highest concentrations in areas other than
      major urban centers. Although AOD is a highly significant predictor of PM(2.5),
      meteorologic parameters are major contributors to the better performance of the
      AOD model. CONCLUSIONS: GOES aerosol/smoke product (GASP) AOD is able to
      summarize a set of weather and land use conditions that stratify PM(2.5)
      concentrations into two different spatial patterns. Even if land use regression
      models do not include AOD as a predictor variable, two separate models should be
      fitted to account for different PM(2.5) spatial patterns related to AOD
      availability.

PMID- 19590679
TI  - California wildfires of 2008: coarse and fine particulate matter toxicity.
AB  - BACKGROUND: During the last week of June 2008, central and northern California
      experienced thousands of forest and brush fires, giving rise to a week of severe
      fire-related particulate air pollution throughout the region. California
      experienced PM(10-2.5) (particulate matter with mass median aerodynamic diameter
      > 2.5 mum to < 10 mum; coarse ) and PM(2.5) (particulate matter with mass median
      aerodynamic diameter < 2.5 mum; fine) concentrations greatly in excess of the air
      quality standards and among the highest values reported at these stations since
      data have been collected. OBJECTIVES: These observations prompt a number of
      questions about the health impact of exposure to elevated levels of PM(10-2.5)
      and PM(2.5) and about the specific toxicity of PM arising from wildfires in this
      region. METHODS: Toxicity of PM(10-2.5) and PM(2.5) obtained during the time of
      peak concentrations of smoke in the air was determined with a mouse bioassay and
      compared with PM samples collected under normal conditions from the region during
      the month of June 2007. RESULTS: Concentrations of PM were not only higher during
      the wildfire episodes, but the PM was much more toxic to the lung on an equal
      weight basis than was PM collected from normal ambient air in the region.
      Toxicity was manifested as increased neutrophils and protein in lung lavage and
      by histologic indicators of increased cell influx and edema in the lung.
      CONCLUSIONS: We conclude that the wildfire PM contains chemical components toxic
      to the lung, especially to alveolar macrophages, and they are more toxic to the
      lung than equal doses of PM collected from ambient air from the same region
      during a comparable season.

PMID- 19590680
TI  - The effect of fine and coarse particulate air pollution on mortality: a national
      analysis.
AB  - BACKGROUND: Although many studies have examined the effects of air pollution on
      mortality, data limitations have resulted in fewer studies of both particulate
      matter with an aerodynamic diameter of <or= 2.5 microm (PM(2.5); fine particles)
      and of coarse particles (particles with an aerodynamic diameter > 2.5 and < 10
      microm; PM coarse). We conducted a national, multicity time-series study of the
      acute effect of PM(2.5) and PM coarse on the increased risk of death for all
      causes, cardiovascular disease (CVD), myocardial infarction (MI), stroke, and
      respiratory mortality for the years 1999-2005. METHOD: We applied a city- and
      season-specific Poisson regression in 112 U.S. cities to examine the association
      of mean (day of death and previous day) PM(2.5) and PM coarse with daily deaths.
      We combined the city-specific estimates using a random effects approach, in
      total, by season and by region. RESULTS: We found a 0.98% increase [95%
      confidence interval (CI), 0.75-1.22] in total mortality, a 0.85% increase (95%
      CI, 0.46-1.24) in CVD, a 1.18% increase (95% CI, 0.48-1.89) in MI, a 1.78%
      increase (95% CI, 0.96-2.62) in stroke, and a 1.68% increase (95% CI, 1.04-2.33)
      in respiratory deaths for a 10-microg/m(3) increase in 2-day averaged PM(2.5).
      The effects were higher in spring. For PM coarse, we found significant but
      smaller increases for all causes analyzed. CONCLUSIONS: We conclude that our
      analysis showed an increased risk of mortality for all and specific causes
      associated with PM(2.5), and the risks are higher than what was previously
      observed for PM(10). In addition, coarse particles are also associated with more
      deaths.

PMID- 19590681
TI  - Limitations of remotely sensed aerosol as a spatial proxy for fine particulate
      matter.
AB  - BACKGROUND: Recent research highlights the promise of remotely sensed aerosol
      optical depth (AOD) as a proxy for ground-level particulate matter with
      aerodynamic diameter <or= 2.5 microm (PM(2.5)). Particular interest lies in
      estimating spatial heterogeneity using AOD, with important application to
      estimating pollution exposure for public health purposes. Given the correlations
      reported between AOD and PM(2.5), it is tempting to interpret the spatial
      patterns in AOD as reflecting patterns in PM(2.5). OBJECTIVES: We evaluated the
      degree to which AOD can help predict long-term average PM(2.5) concentrations for
      use in chronic health studies. METHODS: We calculated correlations of AOD and
      PM(2.5) at various temporal aggregations in the eastern United States in 2004 and
      used statistical models to assess the relationship between AOD and PM(2.5) and
      the potential for improving predictions of PM(2.5) in a subregion, the mid
      Atlantic. RESULTS: We found only limited spatial associations of AOD from three
      satellite retrievals with daily and yearly PM(2.5). The statistical modeling
      shows that monthly average AOD poorly reflects spatial patterns in PM(2.5)
      because of systematic, spatially correlated discrepancies between AOD and
      PM(2.5). Furthermore, when we included AOD as a predictor of monthly PM(2.5) in a
      statistical prediction model, AOD provided little additional information in a
      model that already accounts for land use, emission sources, meteorology, and
      regional variability. CONCLUSIONS: These results suggest caution in using spatial
      variation in currently available AOD to stand in for spatial variation in ground
      level PM(2.5) in epidemiologic analyses and indicate that when PM(2.5) monitoring
      is available, careful statistical modeling outperforms the use of AOD.

PMID- 19590682
TI  - Oral exposure to bisphenol a increases dimethylbenzanthracene-induced mammary
      cancer in rats.
AB  - BACKGROUND: Bisphenol A (BPA) is widely used in the manufacture of polycarbonate
      plastics, including infant formula bottles. OBJECTIVES: Based on the reported
      endocrine disruptor activity of this polyphenol, we hypothesized that exposure to
      BPA early in life would elicit developmental changes in the mammary tissue and
      cause a predisposition for mammary cancer. METHODS: We exposed
      neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally
      with 0, 25, and 250 mug BPA/kg body weight/day. For tumorigenesis studies, female
      offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at
      50 days of age. RESULTS: The combination of DMBA treatment with lactational
      exposure to BPA demonstrated a dose-dependent increase in mammary tumor
      multiplicity and reduced tumor latency compared with controls. In the absence of
      DMBA treatment, lactational BPA exposure resulted in increased cell proliferation
      and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA
      treatment). Using Western blot analysis, we determined that steroid receptor
      coactivators (SRCs) 1-3, Akt, phosphorylated Akt, progesterone receptor A (PR-A),
      and erbB3 proteins were significantly up-regulated at 50 days of age.
      CONCLUSIONS: The data presented here provide the first evidence that maternal
      exposure to BPA during lactation increases mammary carcinogenesis in a DMBA
      induced model of rodent mammary cancer. Changes in PR-A, SRC 1-3, erbB3, and Akt
      activity are consistent with increased cell proliferation and decreased apoptosis
      playing a role in mammary cancer susceptibility. These alterations provide an
      explanation of enhanced mammary carcinogenesis after lactational BPA exposure.

PMID- 19590684
TI  - Do perfluoroalkyl compounds impair human semen quality?
AB  - BACKGROUND: Perfluoroalkyl acids (PFAAs) are found globally in wildlife and
      humans and are suspected to act as endocrine disruptors. There are no previous
      reports of PFAA levels in adult men from Denmark or of a possible association
      between semen quality and PFAA exposure. OBJECTIVES: We investigated possible
      associations between PFAAs and testicular function. We hypothesized that higher
      PFAA levels would be associated with lower semen quality and lower testosterone
      levels. METHODS: We analyzed serum samples for levels of 10 different PFAAs and
      reproductive hormones and assessed semen quality in 105 Danish men from the
      general population (median age, 19 years). RESULTS: Considerable levels of
      perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and
      perfluorohexane sulfonic acid were found in all young men (medians of 24.5, 4.9,
      and 6.6 ng/mL, respectively). Men with high combined levels of PFOS and PFOA had
      a median of 6.2 million normal spermatozoa in their ejaculate in contrast to 15.5
      million among men with low PFOS-PFOA (p = 0.030). In addition, we found
      nonsignificant trends with regard to lower sperm concentration, lower total sperm
      counts, and altered pituitary-gonadal hormones among men with high PFOS-PFOA
      levels. CONCLUSION: High PFAA levels were associated with fewer normal sperm.
      Thus, high levels of PFAAs may contribute to the otherwise unexplained low semen
      quality often seen in young men. However, our findings need to be corroborated in
      larger studies.

PMID- 19590683
TI  - Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal
      parathion exposure on acetylcholine systems in rat brain regions.
AB  - BACKGROUND: Developmental exposure to a wide variety of developmental
      neurotoxicants, including organophosphate pesticides, evokes late-emerging and
      persistent abnormalities in acetylcholine (ACh) systems. We are seeking
      interventions that can ameliorate or reverse the effects later in life.
      OBJECTIVES: We administered parathion to neonatal rats and then evaluated whether
      a high-fat diet begun in adulthood could reverse the effects on ACh systems.
      METHODS: Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2
      mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half
      the animals were switched to a high-fat diet for 8 weeks. We assessed three
      indices of ACh synaptic function: nicotinic ACh receptor binding, choline
      acetyltransferase activity, and hemicholinium-3 binding. Determinations were
      performed in brain regions comprising all the major ACh projections and cell
      bodies. RESULTS: Neonatal parathion exposure evoked widespread abnormalities in
      ACh synaptic markers, encompassing effects in brain regions possessing ACh
      projections and ACh cell bodies. In general, males were affected more than
      females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were
      reversed by the high-fat diet. CONCLUSIONS: A high-fat diet reverses
      neurodevelopmental effects of neonatal parathion exposure on ACh systems. This
      points to the potential for nonpharmacologic interventions to offset the effects
      of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits
      evoked by environmental exposures may thus engender a later preference for a high
      fat diet to maintain normal ACh function, ultimately contributing to obesity.

PMID- 19590686
TI  - Postural changes in blood pressure associated with interactions between candidate
      genes for chronic respiratory diseases and exposure to particulate matter.
AB  - BACKGROUND: Fine particulate matter [aerodynamic diameter </= 2.5 mum (PM(2.5))]
      has been associated with autonomic dysregulation. OBJECTIVE: We hypothesized that
      PM(2.5) influences postural changes in systolic blood pressure (DeltaSBP) and in
      diastolic blood pressure (DeltaDBP) and that this effect is modified by genes
      thought to be related to chronic lung disease. METHODS: We measured blood
      pressure in participants every 3-5 years. DeltaSBP and DeltaDBP were calculated
      as sitting minus standing SBP and DBP. We averaged PM(2.5) over 48 hr before
      study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes.
      To address multiple comparisons, data were stratified into a split sample. In the
      discovery cohort, the effects of SNP x PM(2.5) interactions on DeltaSBP and
      DeltaDBP were analyzed using mixed models with subject-specific random
      intercepts. We defined positive outcomes as p < 0.1 for the interaction; we
      analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025
      with the same sign. Confirmed associations were analyzed within the full cohort
      in models adjusted for anthropometric and lifestyle factors. RESULTS: Nine
      hundred forty-five participants were included in our analysis. One interaction
      with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater
      DeltaDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and
      rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor,
      type 2 (ITPR2) were associated with significantly greater DeltaSBP. Because SNPs
      associated with DeltaSBP in our analysis are in genes along the renin-angiotensin
      pathway, we then examined medications affecting that pathway and observed
      significant interactions for angiotensin receptor blockers but not angiotensin
      converting enzyme inhibitors with PM(2.5). CONCLUSIONS: PM(2.5) influences blood
      pressure and autonomic function. This effect is modified by genes and drugs that
      also act along this pathway.

PMID- 19590685
TI  - Increased expression of histone proteins during estrogen-mediated cell
      proliferation.
AB  - BACKGROUND: There is concern about the potential risk posed by compounds with
      estrogen-like activity present in the environment. As previous studies have shown
      that combined exposure to such compounds results in dose additivity, it should be
      possible to assess estrogen exposure with suitable biomarkers of effect.
      OBJECTIVES: Our goal was to identify candidate protein biomarkers of effect for
      estrogenic compounds. METHODS: In the search for biomarkers, we assessed the
      effect of several estrogenic compounds on the expression profile of proteins in
      breast-derived cell lines varying in their estrogen receptor (ER) phenotype using
      surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. We
      identified responsive proteins, after separating them by SDS-polyacrylamide gel
      electrophoresis, and analyzing the trypsin-digested proteins by tandem mass
      spectrometry. RESULTS: The estrogenic compounds 17beta-estradiol, genistein,
      bisphenol A, and endosulfan produced similar protein profile changes in MCF-7
      cells (phenotype: ERalpha(+)/ERbeta(+)), but had no effect on MDA-MB-231
      (ERalpha(-)/ERbeta(+)), MCF-10F (ERalpha(-)/ERbeta(+)), or MCF-10A (ERalpha(
      )/ERbeta(-)) cells. The most responsive proteins in MCF-7 cells were identified
      as histones H2A, H2B, H3, and H4. Histone levels were not increased in cell lines
      that showed no proliferative response to estrogens despite their rapid intrinsic
      growth rate in culture. CONCLUSION: Our results indicate that ER-mediated cell
      proliferation results in up-regulation of core histone proteins.

PMID- 19590687
TI  - A proton magnetic resonance spectroscopy study of the chronic lead effect on the
      Basal ganglion and frontal and occipital lobes in middle-age adults.
AB  - BACKGROUND: Lead is known to be a health hazard to the human brain and nervous
      system based on data from epidemiologic studies. However, few studies have
      examined the mechanism or biochemical changes caused by lead in the human brain,
      although recently some have used magnetic resonance spectroscopy (MRS) to test
      brain metabolism in vivo. OBJECTIVES: In this study, we used 3-T MRS to
      investigate brain metabolism in workers chronically exposed to lead and matched
      nonexposed controls. MATERIALS:  METHODS: Twenty-two workers at a lead paint
      factory served as chronically exposed subjects of this study. These workers did
      not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy
      volunteers served as controls. We measured blood and bone lead and used a 3-T MRS
      to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and
      total creatine (tCr). A structural questionnaire was used to collect demographic,
      work, and health histories and information about their life habits. RESULTS: All
      the MRS measures were lower in the lead-exposed group. Increased blood and bone
      lead levels correlated with declines in Cho:tCr ratios, especially in the
      occipital lobe, where changes in all gray, subcortical, and white matter were
      significant. Increases in blood and patella lead in every layer of the frontal
      lobe correlated with significant decreases in NAA:tCr ratios. One of the
      strongest regression coefficients was -0.023 (SE = 0.005, p < 0.001), which was
      found in the NAA:tCr ratio of frontal gray matter. DISCUSSION: We conclude that
      chronic exposure to lead might upset brain metabolism, especially NAA:tCr and
      Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone
      lead levels, suggesting that lead induces neuronal and axonal damage or loss. The
      most significant changes occurred in frontal and occipital lobes, areas in which
      previous neurobehavioral studies have shown memory and visual performance to be
      adversely affected by lead toxicity.

PMID- 19590688
TI  - Evidence that humans metabolize benzene via two pathways.
AB  - BACKGROUND: Recent evidence has shown that humans metabolize benzene more
      efficiently at environmental air concentrations than at concentrations > 1 ppm.
      This led us to speculate that an unidentified metabolic pathway was mainly
      responsible for benzene metabolism at ambient levels. OBJECTIVE: We statistically
      tested whether human metabolism of benzene is better fitted by a kinetic model
      having two pathways rather than one. METHODS: We fit Michaelis-Menten-like models
      to levels of urinary benzene metabolites and the corresponding air concentrations
      for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from
      less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm
      and 8.97 ppm, respectively. RESULTS: Using values of Akaike's information
      criterion obtained under the two models, we found strong statistical evidence
      favoring two metabolic pathways, with respective affinities (benzene air
      concentrations analogous to K(m) values) of 301 ppm for the low-affinity pathway
      (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high
      affinity pathway (unknown). The exposure-specific metabolite level predicted by
      our two-pathway model at nonsaturating concentrations was 184 muM/ppm of benzene,
      a value close to an independent estimate of 194 muM/ppm for a typical nonsmoking
      Chinese female. Our results indicate that a nonsmoking woman would metabolize
      about three times more benzene from the ambient environment under the two-pathway
      model (184 muM/ppm) than under the one-pathway model (68.6 muM/ppm). In fact, 73%
      of the ambient benzene dose would be metabolized via the unidentified high
      affinity pathway. CONCLUSION: Because regulatory risk assessments have assumed
      nonsaturating metabolism of benzene in persons exposed to air concentrations well
      above 10 ppm, our findings suggest that the true leukemia risks could be
      substantially greater than currently thought at ambient levels of exposure-about
      3-fold higher among nonsmoking females in the general population.

PMID- 19590689
TI  - Biological monitoring for depleted uranium exposure in U.S. Veterans.
AB  - BACKGROUND: As part of an ongoing medical surveillance program for U.S. veterans
      exposed to depleted uranium (DU), biological monitoring of urine uranium (U)
      concentrations is offered to any veteran of the Gulf War and those serving in
      more recent conflicts (post-Gulf War veterans). OBJECTIVES: Since a previous
      report of surveillance findings in 2004, an improved methodology for
      determination of the isotopic ratio of U in urine ((235)U:(238)U) has been
      developed and allows for more definitive evaluation of DU exposure. This report
      updates previous findings. METHODS: Veterans provide a 24-hr urine specimen and
      complete a DU exposure questionnaire. Specimens are sent to the Baltimore
      Veterans Affairs Medical Center for processing. Uranium concentration and
      isotopic ratio are measured using ICP-MS at the Armed Forces Institute of
      Pathology. RESULTS: Between January 2003 and June 2008, we received 1,769 urine
      specimens for U analysis. The mean urine U measure was 0.009 microg U/g
      creatinine. Mean urine U concentrations for Gulf War and post-Gulf War veterans
      were 0.008 and 0.009 microg U/g creatinine, respectively. Only 3 of the 1,700
      (0.01%) specimens for which we completed isotopic determination showed evidence
      of DU. Exposure histories confirmed that these three individuals had been
      involved in "friendly fire" incidents involving DU munitions or armored vehicles.
      CONCLUSIONS: No urine U measure with a "depleted" isotopic signature has been
      detected in U.S. veterans without a history of retained DU embedded fragments
      from previous injury. These findings suggest that future DU-related health harm
      is unlikely in veterans without DU fragments.

PMID- 19590690
TI  - Emergency admissions for cardiovascular and respiratory diseases and the chemical
      composition of fine particle air pollution.
AB  - BACKGROUND: Population-based studies have estimated health risks of short-term
      exposure to fine particles using mass of PM(2.5) (particulate matter <or= 2.5
      microm in aerodynamic diameter) as the indicator. Evidence regarding the toxicity
      of the chemical components of the PM(2.5) mixture is limited. OBJECTIVE: In this
      study we investigated the association between hospital admission for
      cardiovascular disease (CVD) and respiratory disease and the chemical components
      of PM(2.5) in the United States. METHODS: We used a national database comprising
      daily data for 2000-2006 on emergency hospital admissions for cardiovascular and
      respiratory outcomes, ambient levels of major PM(2.5) chemical components
      [sulfate, nitrate, silicon, elemental carbon (EC), organic carbon matter (OCM),
      and sodium and ammonium ions], and weather. Using Bayesian hierarchical
      statistical models, we estimated the associations between daily levels of PM(2.5)
      components and risk of hospital admissions in 119 U.S. urban communities for 12
      million Medicare enrollees (>or= 65 years of age). RESULTS: In multiple-pollutant
      models that adjust for the levels of other pollutants, an interquartile range
      (IQR) increase in EC was associated with a 0.80% [95% posterior interval (PI),
      0.34-1.27%] increase in risk of same-day cardiovascular admissions, and an IQR
      increase in OCM was associated with a 1.01% (95% PI, 0.04-1.98%) increase in risk
      of respiratory admissions on the same day. Other components were not associated
      with cardiovascular or respiratory hospital admissions in multiple-pollutant
      models. CONCLUSIONS: Ambient levels of EC and OCM, which are generated primarily
      from vehicle emissions, diesel, and wood burning, were associated with the
      largest risks of emergency hospitalization across the major chemical constituents
      of PM(2.5).

PMID- 19590691
TI  - Dopamine transporter genetic variants and pesticides in Parkinson's disease.
AB  - BACKGROUND: Research suggests that independent and joint effects of genetic
      variability in the dopamine transporter (DAT) locus and pesticides may influence
      Parkinson's disease (PD) risk. MATERIALS:  METHODS: In 324 incident PD patients
      and 334 population controls from our rural California case-control study, we
      genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' variable
      number of tandem repeats (VNTR). Using geographic information system methods, we
      determined residential exposure to agricultural maneb and paraquat applications.
      We also collected occupational pesticide use data. Employing logistic regression,
      we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number
      of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility
      allele-pesticide interactions. RESULTS: PD risk was increased separately in DAT A
      clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI),
      1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57),
      and our data suggest a gene dosing effect. Importantly, high exposure to paraquat
      and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR =
      2.99; 95% CI, 0.88-10.2), and in carriers of two or more alleles more than 4-fold
      (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational
      pesticide measures. DISCUSSION: Using two independent pesticide measures, we a)
      replicated previously reported gene-environment interactions between DAT genetic
      variants and occupational pesticide exposure in men and b) overcame previous
      limitations of nonspecific pesticide measures and potential recall bias by
      employing state records and computer models to estimate residential pesticide
      exposure. CONCLUSION: Our results suggest that DAT genetic variability and
      pesticide exposure interact to increase PD risk.

PMID- 19590692
TI  - Progression from beryllium exposure to chronic beryllium disease: an analytic
      model.
AB  - BACKGROUND: Understanding the progression from beryllium exposure (BeE) to
      chronic beryllium disease (CBD) is essential for optimizing screening and early
      intervention to prevent CBD. METHODS: We developed an analytic markov model of
      progression to cbd that assigns annual probabilities for progression through
      three states: from BeE to beryllium sensitization and then to CBD. We used
      calculations of the number in each state over time to assess which of several
      alternative progression models are most consistent with the limited available
      empirical data on prevalence and incidence. We estimated cost-effectiveness of
      screening considering both incremental (cost/case) and cumulative program costs.
      RESULTS: No combination of parameters for a simple model in which risk of
      progression remains constant over time can meet the empirical constraints of
      relatively frequent early cases and continuing development of new cases with long
      latencies. Modeling shows that the risk of progression is initially high and then
      declines over time. Also, it is likely that there are at least two populations
      that differ significantly in risk. The cost-effectiveness of repetitive screening
      declines over time, although new cases will still be found with long latencies.
      However, screening will be particularly cost-effective when applied to persons
      with long latencies who have not been previously screened. CONCLUSIONS: To
      optimize use of resources, the intensity of screening should decrease over time.
      Estimation of lifetime cumulative CBD risk should consider the declining risk of
      progression over time.

PMID- 19590693
TI  - Trends in respiratory symptoms of firefighters exposed to the world trade center
      disaster: 2001-2005.
AB  - BACKGROUND: Respiratory symptoms, either newly reported after the World Trade
      Center (WTC) disaster on 11 September 2001 (9/11) or increased in severity, have
      been well documented in WTC-exposed workers and New York City residents. However,
      considerable uncertainty exists over the persistence of symptoms. OBJECTIVES: In
      this study, our goals were to describe trends in post-9/11 respiratory and gastro
      esophageal reflux disease (GERD) symptoms in WTC-exposed firefighters and to
      examine symptom progression in the cohort that completed both year 1 and year 4
      questionnaires. METHODS: We analyzed questionnaire responses from 10,378
      firefighters in yearly intervals, from 2 October 2001 to 11 September 2005,
      defining exposure based on arrival time at the WTC site. For the cohort of 3,722
      firefighters who completed the two questionnaires, we also calculated exposure
      duration summing months of work at the site. RESULTS: In cross-sectional
      analyses, the prevalence of dyspnea, wheeze, rhinosinusitis, and GERD remained
      relatively stable, whereas cough and sore throat declined, especially between 1
      and 2 years post-9/11. We found a dose-response relationship between arrival time
      and symptoms in all years (p < 0.01). Logistic models of symptoms at year 4 in
      the cohort demonstrated independent effects of earlier arrival and longer work
      duration: each additional month of work increased the odds of symptoms 8-11%.
      CONCLUSIONS: Protracted work exposures increased the odds of respiratory and GERD
      symptoms 4 years later. In most large disasters, exposures may be unavoidable
      during the rescue phase, but our data strongly suggest the need to minimize
      additional exposures during recovery and cleanup phases.

PMID- 19590694
TI  - Perturbation of defense pathways by low-dose arsenic exposure in zebrafish
      embryos.
AB  - BACKGROUND: Exposure to arsenic is a critical risk factor in the complex
      interplay among genetics, the environment, and human disease. Despite the
      potential for in utero exposure, the mechanism of arsenic action on vertebrate
      development and disease is unknown. OBJECTIVES: The objective of this study was
      to identify genes and gene networks perturbed by arsenic during development in
      order to enhance understanding of the molecular mechanisms of arsenic action.
      METHODS: We exposed zebrafish embryos at 0.25-1.25 hr postfertilization to 10 or
      100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome
      microarrays and to test levels of gene expression changes by quantitative real
      time polymerase chain reaction (QPCR). Computational analysis was used to
      identify gene expression networks perturbed by arsenic during vertebrate
      development. RESULTS: We identified a set of 99 genes that responded to low
      levels of arsenic. Nineteen of these genes were predicted to function in a common
      regulatory network that was significantly associated with immune response and
      cancer (p < 10(-41)). Arsenic-mediated expression changes were validated by QPCR.
      CONCLUSIONS: In this study we demonstrated that arsenic significantly down
      regulates expression levels of multiple genes potentially critical for regulating
      the establishment of an immune response. The data also provide molecular evidence
      consistent with phenotypic observations reported in other model systems.
      Additional mechanistic studies will help explain molecular events regulating
      early stages of the immune system and long-term consequences of arsenic-mediated
      perturbation of this system during development.

PMID- 19590695
TI  - Pneumoconiosis from agricultural dust exposure among young California
      farmworkers.
AB  - BACKGROUND: Agricultural workers are exposed to airborne pollutants, including
      organic and inorganic (mineral) dusts. OBJECTIVES: Lung autopsy specimens from
      consecutive coroner's cases of Hispanic males in Fresno County, California, (n =
      112) were obtained to determine whether mineral dust exposure in agricultural
      work leads to pneumoconiosis. METHODS: The left lung was fixed by inflation. We
      evaluated airway and parenchymal pathology using standardized diagnostic criteria
      and semiquantitative grading schemata, including the grading of small airways for
      fibrosis and birefringent mineral dust particles. We analyzed lung dust burden on
      a subset of 37 lungs following bleach digestion, using scanning electron
      microscopy (SEM), X-ray spectrometry (XRS) and image analysis, and by X-ray
      diffraction for crystalline silica (CSi). Farmworkers comprised 51.5% and
      nonfarmworkers 48.5% of the samples. RESULTS: Proximal airways demonstrated
      little mineral dust accumulation, but membranous and respiratory bronchioles had
      wall thickening, remodeling, and inflammation associated with carbonaceous and
      mineral dust deposition. These changes were independently associated with
      agricultural work, cigarette smoking, and increased age. Mineral dust small
      airways disease, pneumoconiosis (macules and nodules), and pathologic changes
      consistent with chronic bronchitis, emphysema, and interstitial fibrosis
      predominated in farmworkers compared with nonfarmworkers. CSi, determined
      gravimetrically, and aluminum silicate particles, determined by SEM/XRS, were
      increased in the lungs of farmworkers compared with nonfarmworkers and were
      significantly (p < 0.05) associated with small airway disease and pneumoconiosis.
      CONCLUSION: Mineral dust exposure is associated with increased small airway
      disease and pneumoconiosis among California farmworkers; however, the clinical
      significance and natural history of these changes remains to be determined.

PMID- 19590696
TI  - Effects of ambient air pollution on hemostasis and inflammation.
AB  - BACKGROUND: Air pollution has consistently been associated with increased
      morbidity and mortality due to respiratory and cardiovascular disease. Underlying
      biological mechanisms are not entirely clear, and hemostasis and inflammation are
      suggested to be involved. OBJECTIVES: Our aim was to study the association of the
      variation in local concentrations of airborne particulate matter (PM) with
      aerodynamic diameter < 10 mum, carbon monoxide, nitrogen monoxide, nitrogen
      dioxide, and ozone with platelet aggregation, thrombin generation, fibrinogen,
      and C-reactive protein (CRP) levels in healthy individuals. METHODS: From 40
      healthy volunteers, we collected 13 consecutive blood samples within a 1-year
      period and measured light-transmittance platelet aggregometry, thrombin
      generation, fibrinogen, and CRP. We performed regression analysis using
      generalized additive models to study the association between the hemostatic and
      inflammatory variables, and local environmental concentrations of air pollutants
      for time lags within 24 hr before blood sampling or 24-96 hr before blood
      sampling. RESULTS: In general, air pollutants were associated with platelet
      aggregation [average, +8% per interquartile range (IQR), p < 0.01] and thrombin
      generation (average, +1% per IQR, p < 0.05). Platelet aggregation was not
      affected by in vitro incubation of plasma with PM. We observed no relationship
      between any of the air pollutants and fibrinogen or CRP levels. CONCLUSIONS: Air
      pollution increased platelet aggregation as well as coagulation activity but had
      no clear effect on systemic inflammation. These prothrombotic effects may partly
      explain the relationship between air pollution and the risk of ischemic
      cardiovascular disease.

PMID- 19590697
TI  - Parental exposure to pesticides and childhood brain cancer: U.S. Atlantic coast
      childhood brain cancer study.
AB  - BACKGROUND: The etiology of childhood brain cancer remains largely unknown.
      However, previous studies have yielded suggestive associations with parental
      pesticide use. OBJECTIVES: We aimed to evaluate parental exposure to pesticides
      at home and on the job in relation to the occurrence of brain cancer in children.
      METHODS: We included 526 one-to-one-matched case-control pairs. Brain cancer
      cases were diagnosed at < 10 years of age, and were identified from statewide
      cancer registries of four U.S. Atlantic Coast states. We selected controls by
      random digit dialing. We conducted computer-assisted telephone interviews with
      mothers. Using information on residential pesticide use and jobs held by fathers
      during the 2-year period before the child's birth, we assessed potential exposure
      to insecticides, herbicides, and fungicides. For each job, two raters
      independently classified the probability and intensity of exposure; 421 pairs
      were available for final analysis. We calculated odds ratios (ORs) and 95%
      confidence intervals (CIs) using conditional logistic regression, after
      adjustment for maternal education. RESULTS: A significant risk of astrocytoma was
      associated with exposures to herbicides from residential use (OR = 1.9; 95% CI,
      1.2-3.0). Combining parental exposures to herbicides from both residential and
      occupational sources, the elevated risk remained significant (OR = 1.8; 95% CI,
      1.1-3.1). We observed little association with primitive neuroectodermal tumors
      (PNET) for any of the pesticide classes or exposure sources considered.
      CONCLUSIONS: Our observation is consistent with a previous literature reporting
      suggestive associations between parental exposure to pesticides and risk of
      astrocytoma in offspring but not PNET. However, these findings should be viewed
      in light of limitations in exposure assessment and effective sample size.

PMID- 19590698
TI  - Residential exposure to polychlorinated biphenyls and organochlorine pesticides
      and risk of childhood leukemia.
AB  - BACKGROUND: Incidence of childhood leukemia in industrialized countries rose
      significantly during 1975-2004, and the reasons for the increase are not
      understood. OBJECTIVES: We used carpet dust as an exposure indicator to examine
      the risk of childhood leukemia in relation to residential exposure to persistent
      organochlorine chemicals: six polychlorinated biphenyl (PCB) congeners and the
      pesticides alpha- and gamma-chlordane, p,p'-DDT
      (dichlorodiphenyltrichloroethane), p,p'-DDE (dichlorodiphenyldichloroethylene),
      methoxychlor, and pentachlorophenol. METHODS: We conducted a population-based
      case-control study in 35 counties in northern and central California in 2001
      2006. The study included 184 acute lymphocytic leukemia (ALL) cases 0-7 years of
      age and 212 birth certificate controls matched to cases by birth date, sex, race,
      and Hispanic ethnicity. We collected carpet dust samples from the room where the
      child spent the most time before diagnosis (similar date for controls) using a
      specialized vacuum. RESULTS: Detection of any PCB congener in the dust conferred
      a 2-fold increased risk of ALL [odds ratio (OR) = 1.97; 95% confidence interval
      (CI), 1.22-3.17]. Compared with those in the lowest quartile of total PCBs, the
      highest quartile was associated with about a 3-fold risk (OR = 2.78; 95% CI, 1.41
      5.48), and the positive trend was significant (p = 0.017). Significant positive
      trends in ALL risk were apparent with increasing concentrations of PCB congeners
      118, 138, and 153. We observed no significant positive associations for
      chlordane, DDT, DDE, methoxychlor, or pentachlorophenol. The associations with
      PCBs were stronger among non-Hispanic whites than among Hispanics despite similar
      distributions of PCB levels among controls in each racial/ethnic group.
      CONCLUSIONS: Our findings suggest that PCBs, which are considered probable human
      carcinogens and cause perturbations of the immune system, may represent a
      previously unrecognized risk factor for childhood leukemia.

PMID- 19590700
TI  - F(2)-isoprostanes as novel biomarkers for type 2 diabetes: a review.
AB  - Oxidative stress (OS) has been implicated as one of the major underlying
      mechanisms behind many acute and chronic diseases. However, the measurement of
      free radicals or their end products is complicated. Isoprostanes, derived from
      the non-enzymatic peroxidation of arachidonic acid are now considered to be
      reliable biomarkers of oxidant stress in the human body. Isoprostanes are
      involved in many of the human diseases such as type 2 diabetes. In type 2
      diabetes elevated levels of F(2)-Isoprostanes (F(2)-IsoPs) have been observed.
      The measurement of bioactive F(2)-IsoPs levels offers a unique noninvasive
      analytical tool to study the role of free radicals in physiology, oxidative
      stress-related diseases, and acute or chronic inflammatory conditions.
      Measurement of oxidative stress by various other methods lacks specificity and
      sensitivity. This review aims to shed light on the implemention of F(2)-IsoPs
      measurement as a gold-standard biomarker of oxidative stress in type 2 diabetics.

PMID- 19590699
TI  - Thyroid hormone levels of pregnant inuit women and their infants exposed to
      environmental contaminants.
AB  - BACKGROUND: An increasing number of studies have shown that several ubiquitous
      environmental contaminants possess thyroid hormone-disrupting capacities.
      Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has
      also been associated with adverse neurodevelopmental effects in infants.
      OBJECTIVES: In this study we examined the relationship between exposure to
      potential thyroid hormone-disrupting toxicants and thyroid hormone status in
      pregnant Inuit women from Nunavik and their infants within the first year of
      life. METHODS: We measured thyroid hormone parameters [thyroid stimulating
      hormone (TSH), free thyroxine (fT(4)), total triiodothyronine (T(3)), thyroxine
      binding globulin (TBG)] and concentrations of several contaminants [PCB-153,
      hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and
      hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical
      cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130).
      RESULTS: In pregnant women, we found a positive association between HO-PCBs and
      T(3) concentrations (beta = 0.57, p = 0.02). In umbilical cord blood, PCB-153
      concentrations were negatively associated with TBG levels (beta = -0.26, p =
      0.01). In a subsample analysis, a negative relationship was also found between
      maternal PCP levels and cord fT(4) concentrations in neonates (beta = -0.59, p =
      0.02). No association was observed between contaminants and thyroid hormones at 7
      months of age. CONCLUSION: Overall, there is little evidence that the
      environmental contaminants analyzed in this study affect thyroid hormone status
      in Inuit mothers and their infants. The possibility that PCP may decrease
      thyroxine levels in neonates requires further investigation.

PMID- 19590701
TI  - The expression of heme oxygenase-1 induced by lansoprazole.
AB  - Our previous studies have demonstrated that lansoprazole inhibits acute
      inflammatory reactions as well as intestinal mucosal injuries induced by ischemia
      reperfusion or indomethacin administration in rats. Thus, proton pump inhibitors
      such as lansoprazole have been demonstrated to prevent gastrointestinal mucosal
      injury by mechanisms independent of acid inhibition. In our in vitro study,
      lansoprazole induced the expression of heme oxygenase-1 (HO-1) on rat gastric
      epithelial cells (RGM-1 cells), and exerted anti-inflammatory effect on the
      dependent of HO-1 expression. Furthermore, NF-E2-related factor-2 (Nrf2) played
      an important role in HO-1 expression induced by lansoprazole. In this review, we
      focused on lansoprazole-induced HO-1 expression, its anti-inflammatory action,
      and the role of Nrf2 in its expression.

PMID- 19590702
TI  - Folate deficiency induces neural stem cell apoptosis by increasing homocysteine
      in vitro.
AB  - Cellular events for neural progenitor cells, such as proliferation and
      differentiation, are regulated by multiple intrinsic and extrinsic cell signals.
      Folate plays a central role in central nervous system development, so folate, as
      an extrinsic signal, may affect neural stem cell (NSC) proliferation and
      differentiation. In the present study, we investigated the effects of folate
      deficiency on the cell proliferation, cell apoptosis and homocysteine
      concentrations in NSCs. NSCs were isolated from fetal rats and identified as NSCs
      by their expression of immunoreactive nestin. Cell proliferation was quantitated
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic
      cells were detected and confirmed by flow cytometric analysis. We measured
      homocysteine concentrations in NSCs by high performance liquid chromatography and
      detected the expression of caspase-3 by western blot method. Folate deficiency
      not only decreased cell proliferation, but also increased the apoptotic rate of
      NSCs as demonstrated by the increased expression of early apoptotic markers such
      as caspase-3, compared to control group (p<0.05). Furthermore, There was a
      statistically significant increase in homocysteine concentration during folate
      deficiency in NSCs (p<0.05). These data suggest that folate affects the cell
      proliferation, apoptosis and homocysteine generation in NSC cells.

PMID- 19590703
TI  - Effects of Oxidized Frying Oil on Proteins Related to alpha-Tocopherol Metabolism
      in Rat Liver.
AB  - An oxidized frying oil (OFO) diet has been reported to induce an increase in
      lipid peroxidation and a reduction in vitamin E status in animal tissues. This
      study was performed to investigate how vitamin E metabolism is influenced by OFO.
      Male Wistar rats were divided into three groups, a control group (CO) and two OFO
      fed groups (OF and OFE). The diet of the OFE group was supplemented with an extra
      50 mg/kg of alpha-tocopherol acetate and thus contained twice as much vitamin E
      as that of the OF group. After six weeks on these diets, liver alpha-tocopherol
      levels in the OF group were the significantly lowest among the three groups.
      Excretion of the alpha-tocopherol metabolite, alpha-carboxyethyl hydroxychroman
      (alpha-CEHC) in the urine was significantly lower in the OF group than in the
      other two groups. There were no significant differences in protein levels of
      alpha-tocopherol transfer protein (alpha-TTP) and multidrug resistance protein
      among the three groups. Protein levels of cytochrome P450 monooxygenase (CYP) 3A,
      CYP4A, and catalase were markedly increased in both groups on the OFO diet. This
      suggests that an OFO diet may interfere with medicine metabolism and needs
      further investigation.

PMID- 19590704
TI  - A rice bran oil diet improves lipid abnormalities and suppress hyperinsulinemic
      responses in rats with streptozotocin/nicotinamide-induced type 2 diabetes.
AB  - The aim of this study was to determine the effects of rice bran oil (RBO) on
      lipid metabolism and insulin resistance in rats with streptozotocin/nicotinamide
      induced type 2 diabetes mellitus (T2DM). Rats were divided into two groups: the
      control group (15% soybean oil, contains 0 g gamma-oryzanol and 0 g gamma
      tocotrienol/150 g oil for 5 weeks) and the RBO group (15% RBO, contains 5.25 g
      gamma-oryzanol and 0.9 g gamma-tocotrienol/150 g oil for 5 weeks). Compared with
      the control group, the RBO group had a lower plasma nonesterified fatty acid
      concentration, ratio of total to high-density-lipoprotein cholesterol, hepatic
      cholesterol concentration, and area under the curve for insulin. The RBO group
      had a higher high-density-lipoprotein cholesterol concentration and greater
      excretion of fecal neutral sterols and bile acid than did the control group. RBO
      may improve lipid abnormalities, reduce the atherogenic index, and suppress the
      hyperinsulinemic response in rats with streptozotocin/nicotinamide-induced T2DM.
      In addition, RBO can lead to increased fecal neutral sterol and bile acid
      excretion.

PMID- 19590705
TI  - Taurine Chloramine Activates Nrf2, Increases HO-1 Expression and Protects Cells
      from Death Caused by Hydrogen Peroxide.
AB  - Hypochlorous acid (HOCl) is toxic and causes cell death. However, this effect is
      inhibited by reaction with taurine, which generates taurine chloramine (TauCl),
      thereby protecting the cells from HOCl-generated toxicity. TauCl has been shown
      to inhibit the production of inflammatory mediators like O(2) (*-), H(2)O(2) and
      NO. In this study, RAW 264.7 macrophages treated with TauCl were protected from
      death caused by H(2)O(2). TauCl increased the expression of peroxiredoxin-1,
      thioredoxin-1 and heme oxygenase (HO)-1, the anti-oxidant enzymes normally
      induced by activation of NF-E2-related factor-2 (Nrf2). TauCl increased nuclear
      translocation of Nrf2 and binding to the anti-oxidant response element. These
      data suggest that TauCl produced abundantly in the activated neutrophils and
      released to surrounding cells in the inflamed tissues may induce the expression
      of cytoprotective anti-oxidant enzymes. Elevation of HO activity via induction of
      HO-1 expression within neighboring cells may provide protection from cytotoxicity
      caused by inflammatory oxidants like H(2)O(2).

PMID- 19590706
TI  - Efficacy of Corrected Rapid Turnover Protein Increment Index (CRII) for Early
      Detection of Improvement of Nutrition Status in Patients with Malnutrition.
AB  - Serum prealbumin level is useful for assessment of changes in nutritional status
      but it is markedly affected by the inflammation. In this study, we examined the
      efficacy of the corrected rapid turnover protein increment index (CRII) for
      prealbumin, which is calculated as [prealbumin level/C-reactive protein (CRP)
      level on the assessment day]/[prealbumin level/CRP level on the day of starting
      nutritional care], for prediction of improvement of nutritional status in
      patients with malnutrition. The subjects were 50 hospitalized patients with low
      albuminemia, who were receiving nutritional care. Serum concentrations of
      albumin, prealbumin and CRP were measured every week for 5 weeks. We defined
      patients whose serum albumin level was elevated by more than 0.2 g/dl after 5
      weeks as those showing improved nutritional status. There was a significant
      difference in the prealbumin level between improved and unimproved patients at 5
      weeks after the start of nutritional support. On the other hand, the prealbumin
      CRII value showed a significant difference between the groups at 1 and 2 weeks
      after the start of nutritional support. In conclusion, assessment of prealbumin
      CRII is useful for early prediction of improved nutritional status in patients
      with malnutrition.

PMID- 19590707
TI  - Antioxidant Activity of Caffeic Acid through a Novel Mechanism under UVA
      Irradiation.
AB  - Effect of caffeic acid on the formation of hydroxyl radicals was examined during
      xanthone-mediated photosensitization. The reaction was performed on irradiation
      (lambda = 365 nm) of the standard reaction mixture containing 15 microM xanthone,
      0.1 M 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and 20 mM phosphate buffer (pH 7.4)
      using electron paramagnetic resonance (EPR) with spin trapping. Caffeic acid
      inhibited the formation of hydroxyl radicals. Caffeic acid hardly scavenged both
      hydroxyl radicals and superoxide radicals under conditions employed in this paper
      in spite of its ability to act as a hydrogen donor or a reagent for the aromatic
      hydroxylation, because high concentration of DMPO trapped hydroxyl radicals
      overwhelmingly. Furthermore, caffeic acid inhibited the formation of hydroxyl
      radicals in the standard reaction mixture with EDTA under UVA irradiation.
      Accordingly, the inhibitory effect of caffeic acid on the formation of hydroxyl
      radicals in the standard reaction mixture under UVA irradiation is not due to its
      ability to chelate iron. Thus, the inhibitory effect of caffeic acid seems to
      occur in the standard reaction mixture under UVA irradiation through a novel
      antioxidation activity, i.e., ability to quench the exited xanthone.

PMID- 19590708
TI  - Predictive factors for the development or regression of Fatty liver in Japanese
      adults.
AB  - Fatty liver is commonly associated with alcohol or metabolic syndrome. We aimed
      to examine the longitudinal aspects of fatty liver, and clarify the independent
      predictors for the development or regression of fatty liver. In the present
      study, the clinical features of 1578 Japanese adults (1208 men and 370 women; 35
      to 69 years of age) who visited our center both in 2000 and 2007-2008 were
      recorded and compared, including liver status diagnosed by ultrasonography. Of
      the 1578 participants, 217 (13.8%) showed fatty liver development, and 74 (4.7%)
      showed fatty liver regression. Logistic regression analysis revealed that body
      mass index and percentage body fat were strongly associated with the development
      or regression of fatty liver. Metabolic syndrome-related disorders such as serum
      levels of total cholesterol, triglyceride, uric acid, and fasting blood glucose
      were also associated with clinical course to some degree. However, the history of
      alcohol intake, the presence of metabolic syndrome, blood pressure, and habitual
      physical exercise were not independent predictors for the development or
      regression of fatty liver. Our present data suggest that control of body weight
      in men and the percentage body fat in women are particularly important for the
      prevention or treatment of fatty liver.

PMID- 19590709
TI  - The Latent Risk of Acidosis in Commercially Available Total Parenteral Nutrition
      (TPN) Products: a Randomized Clinical Trial in Postoperative Patients.
AB  - To evaluate the latent risk of acidosis in commercially available total
      parenteral nutrition (TPN) products, three types of commercially available TPN
      products were compared in postoperative patients. Sixty-four hospitalized
      patients with gastro-intestinal disease who undertook curative gastro intestinal
      resection were studied prospectively and administered with TPN solutions. Three
      types of commercially available TPN products were assigned randomly to eligible
      patients. Serial studies of blood acid-base status, serum electrolytes, and
      urinary acid-base status were conducted in the three groups administered with
      different TPN solutions. Patients received appropriate electrolytic solutions on
      the operation day and TPN solution from 2 to 7 days after operation. There were
      no differences among any of the serum electrolytes in the three groups. In one
      group, urinary pH decreased slightly and urinary net acid excretion (NAE)
      increased significantly after administration. This TPN product contains about 40
      mEq/L of non-metabolizable acid to avoid the Maillard reaction that produces a
      complex of glucose and amino acids. Urinary NAE did not change in the other two
      groups. These TPN products do not use non-metabolizable acid to adjust pH. The
      present results suggest that the non-metabolizable acid may be a risk factor of
      metabolic acidosis.

PMID- 19590710
TI  - Effects of caloric intake on intestinal mucosal morphology and immune cells in
      rats treated with 5-Fluorouracil.
AB  - Anticancer drugs have been reported to damage the intestinal mucosa. We evaluated
      the effects of caloric intake on the mucosal morphology and immune cells in rats
      treated with 5-fluorouracil (5-FU). Rats were received a liquid diet plus 5-FU
      treatment for 8 days as follows: Low calorie group (25 kcal/day with 5-FU),
      Normal calorie group (50 kcal/day with 5-FU), and Control group (50 kcal/day with
      saline). The mucosal morphology, cell numbers and phenotypes of spleen and
      intraepithelial lymphocytes (IEL) were assessed. As compared with the control
      group, the villus heights were significantly lower in the Low calorie group, but
      not significantly lower in the Normal calorie group. The total cell yield from
      the spleen, CD4+ and CD8+ T cells decreased in the Low and Normal calorie group,
      but these changes were less pronounced in Normal calorie group. The total cell
      yield from the IEL also decreased in the Low calorie group, but not in the Normal
      calorie group. Our study demonstrated that sufficient caloric intake attenuated
      the damages in intestinal morphology and in the immune cell numbers. Clinically,
      nutritional support would be expected to be one approach to reducing the risk of
      bacterial translocation or infection induced by chemotherapy.

PMID- 19590711
TI  - Increased lipid absorption and transport in the small intestine of zucker obese
      rats.
AB  - The aim of this study was to compare the potency of intestinal lipid absorption
      in Zucker obese rats compared with Sprague-Dawley (SD) rats. Six male Zucker
      obese (fa/fa) and six male SD rats baring intestinal lymph fistulae were used in
      this study. After 24 h recovery, rats were infused inraduodenally with a lipid
      emulsion containing 40 micromol triolein (labeled with glycerol tri[(3)H
      oleate]), 7.8 micromol phosphatidyl choline in 3 ml phosphate buffered saline at
      a rate of 3 ml/h for 8 h. Lymph samples were collected and the radioactive lipid
      content determined. Apolipoprotein B (apo B) level in the lymph was evaluated.
      The Zucker obese rats transported more radioactive lipid into the lymph compared
      with the SD rats, particularly in the early phase of lipid absorption. Lymph apo
      B levels in the intestinal mucosa were significantly increased compared with the
      SD rats. In conclusion, this study indicated that lipid absorption and transport
      in Zucker obese rats is concomitant with increased apo B levels in the mesenteric
      lymph, indicating that the increase in lipid absorption may be responsible, at
      least in part, for obesity progression and hyperlipidemia.

PMID- 19590712
TI  - Lansoprazole, a Proton Pump Inhibitor, Suppresses Production of Tumor Necrosis
      Factor-alpha and Interleukin-1beta Induced by Lipopolysaccharide and Helicobacter
      Pylori Bacterial Components in Human Monocytic Cells via Inhibition of Activation
      of Nuclear Factor-kappaB and Extracellular Signal-Regulated Kinase.
AB  - Pathogenic bacterial components play critical roles in initiation of
      gastrointestinal inflammation via activation of intracellular signaling pathways
      which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-1beta. Lansoprazole (LANSO), a proton pump inhibitor, has
      been widely used for the treatment of peptic ulcers and reflux esophagitis due to
      its potent acid-suppressive effect. It has also been reported to have anti
      inflammatory effects. In this study we investigated the effects of LANSO on the
      production of TNF-alpha and IL-1beta induced by lipopolysaccharide (LPS) and
      Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line
      (THP-1). LANSO (100 microM) significantly reduced mRNA expression and production
      of TNF-alpha and IL-1beta by THP-1 cells stimulated by LPS and HpWE. LANSO
      inhibited phosphorylation and degradation of inhibitory factor kappaB-alpha
      (IkappaB-alpha) and phosphorylation of extracellular signal-regulated kinase
      (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO
      exerts anti-inflammatory effects by suppressing induction of TNF-alpha and IL
      1beta via inhibition of nuclear factor (NF)-kappaB and ERK activation.

PMID- 19590713
TI  - The Effects of gamma-Aminobutyric Acid, Vinegar, and Dried Bonito on Blood
      Pressure in Normotensive and Mildly or Moderately Hypertensive Volunteers.
AB  - The purpose of this study was to examine the effects of gamma-aminobutyric acid
      (GABA) in fermented drinking water prepared from sodium glutamate, vinegar, and
      dried bonito (FDWG) compared with placebo [vinegar and dried bonito without GABA
      (FDW)] and its safety in normotensive and mildly or moderately hypertensive
      volunteers. A double-blind, placebo-controlled, randomized study was conducted
      involving volunteers with normal (group-N) and mildly or moderately high (group
      H) blood pressure (BP). After a pretreatment period of 2 weeks (weeks -2), the
      subjects received FDWG or FDW for 12 weeks followed by 4 weeks of no intake
      (weeks 16). In group-H, both FDWG and FDW significantly decreased systolic (SBP, 
      7.6 +/- 4.0 and -5.5 +/- 1.5 mmHg, p<0.05, respectively) and diastolic (DBP, 
      10.6 +/- 4.0 and -7.6 +/- 1.7 mmHg, p<0.01, respectively) BP compared to the
      baseline (0-week) value at 12 weeks, respectively. There were no abnormal changes
      in hematological or blood chemistry variables, urinalysis, heart rate, or body
      weight in the study groups. These findings indicated that vinegar and dried
      bonito with or without GABA might have an effect on BP in mildly or moderately
      hypertensive patients.

PMID- 19590714
TI  - Effects of the Cellcultured Acanthopanax senticosus Extract on Antioxidative
      Defense System and Membrane Fluidity in the Liver of Type 2 Diabetes Mouse.
AB  - This study examined the effect of cellcultured Acanthopanax senticosus (A.
      senticosus) extract on the antioxidative defense system, oxidative stress and
      cell membrane fluidity in the liver of type 2 diabetes in the C57BL/6J mouse as
      an animal which is genetically prone to develop insulin resistance and
      obesity/diabetes. C57BL/6J mice were randomly divided, control diet (N-C), high
      fat diet (DM-C), control diet plus A. senticosus extract (N-CASM), and high fat
      diet plus A. senticosus extract (DM-CASM). The mice were orally administered an
      A. senticosus extract (0.5 g/kg body weight) in the N-CASM and DM-CASM groups
      once a day for 12 weeks, and distilled water in the N-C and DM-C groups.
      Cellcultured A. senticosus extract was found to be excellent for strengthening
      the antioxidative defense system, reducing the generation of reactive oxygen
      species (ROS) and damaging oxidative substances, and maintaing membrane fluidity
      (MF) in the liver of type 2 diabetes mouse.

PMID- 19590715
TI  - Asian Society of Gynecologic Oncology (ASGO): a central platform against
      gynecologic cancers in Asia.

PMID- 19590716
TI  - Current status of gynecologic cancer in Japan.
AB  - To make an overview of the current status of gynecologic cancer in Japan, we
      reviewed the recent incidence of cervical, endometrial, and ovarian cancer in
      Japanese women. The incidence of all three cancers has increased, but trends
      differ respectively. In age specific cancer site distribution data, the uterus
      and ovary are leading sites of high incidence among Japanese women younger than
      40 years of age. Therefore, fertility sparing cancer treatment has received much
      attention. Several multicenter clinical trials have been done by Japanese groups,
      and some excellent evidence has been collected for endometrial and ovarian
      cancer. A promising international collaboration trial for ovarian clear cell
      carcinoma is also underway at the present time.

PMID- 19590717
TI  - Current status of gynecological cancer in China.
AB  - The aim of this review is to examine the current status of gynecological cancer
      in China focusing on epidemiological data. Epidemiological data on gynecological
      cancer in China is sparse. Therefore, most of the data were estimated via
      extrapolation based on a few available datasets. Cervical cancer is relatively
      rare and the incidence and mortality rate are largely decreasing. However, in
      young women, the incidence and mortality rates are increasing. The overall and
      age-specific incidence rates of cervical cancer appear to be varied according to
      geographical areas. The overall prevalence rate of human papillomavirus (HPV) in
      China is similar with other eastern Asian countries, but the age-specific HPV
      prevalence showed sustained high HPV prevalence rates in elderly women. There is
      not yet an established national program for cervical cancer prevention. The
      incidence rate of corpus and ovarian cancers in China slightly increased between
      2000 and 2005, but is still lower than Japan or Korea. There is no reliable,
      national-level data on mortality rates of corpus and ovarian cancer in China.
      Breast cancer is one of the most rapidly increasing cancers in China. The
      increase was sharper in young women than in elderly women. Both increased risk
      and change of population size/structure contributed to the increase of breast
      cancer.

PMID- 19590719
TI  - Factors associated with HPV persistence after conization in patients with
      negative margins.
AB  - OBJECTIVE: The clearance rate of human papillomavirus (HPV) after conization is
      generally high, although some HPV infections persist. We investigated the factors
      that affect the clearance of HPV after conization in patients with negative
      margins. METHODS: We retrospectively analyzed 77 patients (mean age 39.9 years,
      range 25 to 51 years) with CIN 2/3 who underwent loop electrosurgical excision
      procedure (LEEP) conization with negative margins. All patients had a Pap smear
      and high-risk (HR) HPV testing using Hybrid Capture II system and HPV DNA chip
      before conization. We used>/=1 relative light units (RLUs) as the cutoff for
      persistence of HPV after conization. RESULTS: High-risk HPV was detected in 73 of
      77 (94.8%) patients before conization. At the 6-months follow-up, the high-risk
      HPV was eliminated in 60 of 73 (82.2%) patients. The HPV persistence rate after
      conization was 17.8% (13/73). Univariate analysis showed that persistent HPV
      infection after conization with negative margins was more likely to occur when
      the pretreatment viral load was high (RLU/positive control >100 (p=0.027) and the
      HPV was type 16 (p=0.021). Logistic regression analysis showed that preoperative
      HPV type 16 infection was the only significant independent factor (p=0.021) for
      HPV persistence out of age, cytology, punch biopsy histology, HPV viral load, and
      conization histology. CONCLUSION: Conization effectively removes HR-HPV
      infection. HPV type 16 infection before conization was significantly related to
      HR-HPV persistence after conization with negative margins. Therefore, patients
      with HPV 16 infection before conization need to be followed closely.

PMID- 19590718
TI  - Role of high risk-human papilloma virus test in the follow-up of patients who
      underwent conization of the cervix for cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To examine whether the presence of high risk-human papilloma virus (HR
      HPV) after conization of the cervix was a risk factor for persistence or
      recurrence of cervical intraepithelial neoplasia (CIN) and whether HR-HPV test
      could be a guideline for post-therapy surveillance. METHODS: The study
      retrospectively analyzed data from 243 patients who underwent LLETZ or CKC of the
      cervix due to CIN. RESULTS: A positive HR-HPV test result which was performed
      between 3 and 6 months after procedure was a risk factor for persistent or
      recurrent cytological (p<0.001, odds ratio [OR]=22.51, 95% confidence interval
      [CI]=9.74-52.02) and pathological (p<0.001, OR=18.28, 95% CI=5.55-60.20)
      abnormalities. CONCLUSION: HR-HPV positive patients between 3 and 6 months after
      procedure should undergo frequent and meticulous post-therapy surveillance, while
      HR-HPV negative patients do not require such high-level surveillance and could
      undergo routine surveillance.

PMID- 19590720
TI  - Efficacy of taxane and platinum-based chemotherapy guided by extreme drug
      resistance assay in patients with epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the efficacy of taxane and platinum-based chemotherapy
      guided by extreme drug resistance assay (EDRA) in patients with epithelial
      ovarian cancer. METHODS: Thirty-nine patients were enrolled, who were diagnosed
      as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and
      received both debulking surgery and EDRA in Asan Medical Center between August
      2004 and August 2006. Another thirty-nine patients were enrolled, who did not
      receive EDRA as control. Paclitaxel 175 mg/m(2) and carboplatin AUC 5 were
      administered as primary combination chemotherapy to both EDRA group and the
      control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m(2)
      if a patient showed extreme drug resistance (EDR) to paclitaxel and not to
      docetaxel. Carboplatin was replaced by cisplatin 75 mg/m(2) if a patient showed
      EDR to carboplatin and not to cisplatin. If only one drug showed low drug
      resistance (LDR), it was allowed to add another drug which showed LDR such as
      gemcitabine 1,000 mg/m(2). CT scan was performed every three cycles and CA-125
      was checked at each cycle. RESULTS: There was no significant difference in
      overall response rate between EDRA group and the control group (84.5% vs. 71.8%,
      p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least
      one drug and its response rate was significantly higher than that of the control
      group (93.3% vs. 71.8%, p=0.023). CONCLUSION: we could choose a combination of
      taxane and platinum which did not show EDR and could obtain a good response in
      the patients with ovarian cancer.

PMID- 19590721
TI  - Prognostic factors of secondary cytoreductive surgery for patients with recurrent
      epithelial ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to identify the prognostic factors of
      secondary cytoreductive surgery on survival in patients with recurrent epithelial
      ovarian cancer. METHODS: The medical records of all patients who underwent
      secondary cytoreductive surgery between May 2001 and October 2007 at the National
      Cancer Center, Korea were reviewed. Univariate and multivariate analyses were
      executed to evaluate the potential variables for overall survival. RESULTS: In
      total, 54 patients met the inclusion criteria. Optimal cytoreduction to <0.5 cm
      residual disease was achieved in 87% of patients who had received secondary
      cytoreductive surgery. Univariate analysis revealed that site of recurrence
      (median survival, 53 months for the largest tumors in the pelvis vs. 24 months
      for the largest tumors except for the pelvis; p=0.007), progression free survival
      (PFS) (median survival, 43 months for PFS>/=12 months vs. 24 months for PFS<12
      months; p=0.036), and number of recurrence sites (median survival, 49 months for
      single recurred tumor vs 29 months for multiple recurred tumors; p=0.036) were
      significantly associated with overall survival. On multivariate analysis,
      prognostic factors that correlated with improved survival were site of recurrence
      (p=0.013), and PFS (p=0.043). CONCLUSION: In the author's analysis, a significant
      survival benefit was identified for the recurred largest tumors within the pelvis
      and PFS>/=12 months. Secondary cytoreductive surgery should be offered in
      selected patients and large prospective studies are needed to define the
      selection criteria for secondary cytoreductive surgery.

PMID- 19590722
TI  - Surgical practice patterns in endometrial cancer: results of the Korean
      Gynecologic Oncology Group survey.
AB  - OBJECTIVE: This study was undertaken to document current practice patterns for
      the surgical treatment of endometrial cancer in Korea. METHODS: Questionnaires
      were distributed to 131 Korean gynecologic oncologists, all members of the Korean
      Gynecologic Oncology Group. Questions addressed extent of hysterectomy procedure,
      pelvic (PEN) or paraaortic (PAN) lymph node dissection, ovarian preservation, and
      omentectomy. RESULTS: Completed questionnaires were returned by 64.1% (84/131) of
      the oncologists at 50 institutes. Extrafascial hysterectomy (EH) was used by 32%
      of respondents and modified radical hysterectomy (MRH) or radical hysterectomy
      (RH) by 17%. Hysterectomy procedures were selectively employed based on tumor
      related factors by 51% of the respondents. Laparoscopic hysterectomy was
      routinely utilized by 49% and was more commonly used by younger surgeons with 10
      years of experience or less. PEN dissection was routinely utilized by 67% and was
      used selectively based on tumor-related factors by 33%. PAN dissection/biopsy was
      used either routinely (43%) or selectively based on tumor-related factors (43%).
      PAN dissection/biopsy had never been employed by 12% of the respondents. Sixty
      nine percent of respondents stated that grossly normal looking ovaries can be
      preserved during surgery in young aged patients with early stage disease, and 29%
      stated that bilateral oophorectomy should be performed irrespective of age or
      stage. Omentectomy was routinely performed by 11% of respondents, and was
      selectively performed when extrauterine spread was present by 41%. CONCLUSION:
      Surgical procedures for the treatment of endometrial cancer are still not
      standardized among Korean gynecologic surgeons. Clinical trials to determine the
      benefits of the different surgical procedures should be developed.

PMID- 19590723
TI  - TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but
      not carboplatin.
AB  - OBJECTIVE: Platinum (Pt) based drugs including cisplatin and carboplatin are
      widely used as anticancer drugs in various human cancers. Many studies have shown
      that chemotherapeutic agents synergistically enhance cell death induced by death
      ligands. However it has been recently reported that cisplatin may inhibit tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death
      through inactivation of caspases. Thus, we investigated whether carboplatin also
      inhibits TRAIL-induced cell death. METHODS: HeLa cells were treated with TRAIL in
      the presence of cisplatin or carboplatin, and cell death was analyzed using the
      crystal violet staining method. Caspase activation was checked through detection
      of Bid cleavage by Western blotting using anti-Bid antibody. RESULTS: Cisplatin
      inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced
      TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid
      cleavage, carboplatin had no effect on caspase-8 activity. CONCLUSION: Although
      cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they
      have the opposite effects on TRAIL-induced cell death.

PMID- 19590724
TI  - Expression and mutational analysis of TGF-beta/Smads signaling in human cervical
      cancers.
AB  - OBJECTIVE: To define the molecular basis of TGF-beta1 function in cervical
      carcinogenesis, we explored the expression and mutational status of TGF-beta1,
      TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling
      pathway, in human cervical cancers. METHODS: Expression of TGF-beta1, TGF-beta1
      receptors, and Smads transcripts were determined by quantitative reverse
      transcription-polymerase chain reaction (RT-PCR), and sequence alteration was
      analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis.
      Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by
      quantitative genomic PCR. RESULTS: Abnormal overexpression of TGF-beta1 and
      abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of
      50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50)
      in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less
      than a half of normal means. In addition, no evidence for sequence alterations of
      the gene was found by RT-PCR-SSCP analysis. CONCLUSION: Our study demonstrates
      that disruption of TGF-beta/Smad signaling pathway exist in human cervical
      cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad
      signaling pathway might contribute to the malignant progression of human cervical
      tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor
      suppression function.

PMID- 19590726
TI  - A case of mucinous adenocarcinoma arising from retroperitoneal teratoma treated
      with chemoradiation.
AB  - Retroperitoneal teratoma with malignant transformation is a rare condition in
      adults. Its most common malignant transformation is into a squamous cell
      carcinoma, but rarely into a mucinous adenocarcinoma. Postoperative treatment of
      mucinous adenocarcinoma arising from teratomas has not been established due to
      its rare incidence. Here we present a case of retroperitoneal mucinous
      adenocarcinoma arising from a teratoma in the presacral area. Operative and
      postoperative managements are described with a brief review of the literatures.

PMID- 19590725
TI  - A case of multiple metastatic low-grade endometrial stromal sarcoma arising from
      an ovarian endometriotic lesion.
AB  - The development of endometrial stromal sarcomas (ESSs) in foci of endometriosis
      is extremely rare, and few cases have been reported in the literature to date,
      particularly with regard to multiple extrauterine ESS. Here we report a case of
      endometrial stromal sarcoma with multiple metastasis that arose from an ovarian
      endometriotic lesion. The literature is also briefly reviewed.

PMID- 19590727
TI  - Metastatic carcinoma of cervix mimicking psoas abscess on imaging: a case report.
AB  - Cervical cancer can be presented as an unusual and aggressive manner in human
      immunodeficiency virus (HIV)-positive women. There are case reports of psoas
      abscess which mimick metastasis from cervical carcinoma in HIV-positive patients.
      However, such cases are very rare in HIV-negative women with only few case
      reports available in the literature. We report one case of psoas abscess
      mimicking metastasis in a HIV-negative woman, which was initially diagnosed as
      spinal tuberculosis.

PMID- 19590728
TI  - Differing prognosis of cervical cancer patients with high risk of treatment
      failure after radical hysterectomy.

PMID- 19590729
TI  - In reply.

PMID- 19590730
TI  - Imitation and communication skills development in children with pervasive
      developmental disorders.
AB  - This study evaluates the correlation between failure to develop spontaneous
      imitation and language skills in pervasive developmental disorders. Sixty-four
      children between the age of 3 and 8 years were assessed using the Autism
      Diagnostic Interview-Revised (ADI-R), the Childhood Autism Rating Scale (CARS),
      and the Autism Diagnostic Observation Schedule (ADOS), as well as direct
      observation of imitation. The sample was subdivided into a verbal and a nonverbal
      group. Analysis of mean scores on the CARS "imitation" items and of ADI-R
      "spontaneous imitation" and "pointing to express interest" revealed a
      statistically significant difference between verbal and nonverbal groups, with
      more severe impairment/higher scores in the nonverbal than the verbal group.
      These results suggest that nonverbal children have specifically impaired
      imitation and pointing skills.

PMID- 19590731
TI  - Adenylate-cyclase activity in platelets of patients with obsessive-compulsive
      disorder.
AB  - Although the main biological hypothesis on the pathophysiology of obsessive
      compulsive disorder (OCD) is centered on the serotonin system, indications are
      available that other neurotransmitters, and even second messengers, particularly
      the cyclic adenosine monophosphate (cAMP) signaling, may be involved, though
      effective data are few. Therefore, the aim of the present study was to evaluate
      and compare the basal and isoprenaline (ISO)-stimulated velocity of adenylate
      cyclase (AC) in human platelet membranes of patients with OCD and healthy control
      subjects. The results showed that the basal and ISO-stimulated AC activity, as
      well as the dose-response curves of ISO by using agonist concentrations ranging
      between 0.1 nM and 10 muM, were not different in the two groups. However, OCD
      patients showed lower EC(50) and higher E(max) values than healthy subjects.
      These findings suggest the presence of supersensitive beta-adrenergic receptors
      in platelets of OCD patients.

PMID- 19590736
TI  - Short bowel patients treated for two years with glucagon-like peptide 2 (GLP-2):
      compliance, safety, and effects on quality of life.
AB  - BACKGROUND AND AIMS: Glucagon-like peptide 2 (GLP-2) has been shown to improve
      intestinal absorption in short bowel syndrome (SBS) patients in a short-term
      study. This study describes safety, compliance, and changes in quality of life in
      11 SBS patients at baseline, week 13, 26, and 52 during two years of subcutaneous
      GLP-2 treatment, 400 microgram TID, intermitted by an 8-week washout period.
      METHODS: Safety and compliance was evaluated during the admissions. The Sickness
      Impact Profile (SIP), Short Form 36 (SF 36), and Inflammatory Bowel Disease
      Questionnaire (IBDQ) evaluated quality of life. RESULTS: The predominant adverse
      event was transient abdominal discomfort in 5 of 11 patients, but in 2, both
      suffering from Crohns disease, it progressed to abdominal pain and led to
      discontinuation of GLP-2 treatment. One had a fibrostenotic lesion electively
      resected at the jejuno-ascendo-anastomosis. The investigator excluded a patient
      due to unreliable feedback. Stoma nipple enlargement was seen in all 9
      jejunostomy patients. Reported GLP-2 compliance was excellent (>93%). GLP-2
      improved the overall quality of life VAS-score (4.1 +/- 2.8 cm versus 6.0 +/- 2.4
      cm, P < .01), the overall SIP score (10.3 +/- 8.9% versus 6.2 +/- 9.5%, P <
      .001), the mental component of the SF-36 (45 +/- 13% versus 53 +/- 11%, P < .05),
      and the overall IBDQ score (5.1 +/- 0.9 versus 5.4 +/- 0.9, P < .007) in the 8
      patients completing the study. CONCLUSIONS: Long-term treatment with GLP-2 is
      feasible in SBS patients, although caution must be exercised in patients with a
      history of abdominal pain. Although conclusions cannot be made in a noncontrolled
      trial, the high reported compliance might reflect a high treatment satisfaction,
      where the clinical benefits of GLP-2 may outweigh the discomforts of injections.

PMID- 19590732
TI  - Olanzapine and fluoxetine combination therapy for treatment-resistant depression:
      review of efficacy, safety, and study design issues.
AB  - Treatment-resistant depression (TRD) is a common occurrence in clinical practice.
      Up to 30% of patients with major depression do not respond to conventional
      antidepressant treatment, while a significantly greater number of patients
      experience only partial symptom reduction. Numerous strategies may be applied by
      the practicing clinician to overcome limitations in the effectiveness of
      antidepressant monotherapy, including combining drug treatment with evidence
      supported psychotherapies, combining antidepressants (combination
      pharmacotherapy), and combining antidepressants with other non-antidepressant
      psychotropic medications (augmentation treatment). One such augmentation
      strategy, the combination of the selective serotonin reuptake inhibitor,
      fluoxetine (FLX), with the atypical antipsychotic drug, olanzapine (OLZ), is
      supported by the results of four randomized, double-blind, acute phase studies of
      patients who had responded inadequately to antidepressant monotherapy. In each
      study, the FLX/OLZ combination caused rapid reduction in Montgomery-Asberg
      Depression Rating scale scores, with two of the four studies showing
      significantly greater improvement than antidepressant monotherapy at study
      endpoint. Effects of the FLX/OLZ combination were strongest in cases where
      failure to respond to two antidepressants prior to randomization was established
      during the current depressive episode. The FLX/OLZ combination was well
      tolerated; however, body weight gain and increases in prolactin were greater than
      that of the antidepressant monotherapy groups, and were comparable to that of OLZ
      monotherapy. While effective during acute-phase treatment, questions remain
      regarding the long-term efficacy and safety of FLX/OLZ relative to antidepressant
      monotherapy and other combination strategies. Efforts aimed at determining the
      placement of FLX/OLZ among the available options for addressing TRD are limited
      by lack of comparison and sequential treatment studies. Important aspects of
      study design and directions for future research are discussed.

PMID- 19590737
TI  - An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol
      haptens.
AB  - The first synthesis of bioactive long alkyl chain 5-n-alkylresorcinols, present
      in whole grain products, by a novel modification of the Wittig reaction is
      described. All the main long chain 5-n-alkylresorcinols present in rye and wheat,
      including C(23) and C(25) analogues and haptens, which have not been previously
      prepared, were synthesised. Microwave-promoted reactions of a semi-stabilized
      ylid and alkanals in water gave good yields in both pressurized and open systems.
      An alternative microwave-promoted synthesis starting from non-stabilized
      alkyltriphenylphosphonium salts and 3,5-dimethoxybenzaldehyde worked as well.
      Aqueous media were suitable for the reactions even if the starting materials were
      not soluble in water. The 5-n-alkylresorcinols are potential biomarkers of whole
      grain intake, and the new hapten derivatives of 5-n-alkylresorcinols will open
      the way for the immunochemical detection techniques of alkylresorcinols.

PMID- 19590739
TI  - Green oxidations: titanium dioxide induced tandem oxidation coupling reactions.
AB  - The application of titanium dioxide as an oxidant in tandem oxidation type
      processes is described. Under microwave irradiation, quinoxalines have been
      synthesized in good yields from the corresponding alpha-hydroxyketones.

PMID- 19590740
TI  - Synthesis and enzymatic evaluation of 2- and 4-aminothiazole-based inhibitors of
      neuronal nitric oxide synthase.
AB  - Highly potent and selective inhibitors of neuronal nitric oxide synthase (nNOS)
      possessing a 2-aminopyridine group were recently designed and synthesized in our
      laboratory and were shown to have significant in vivo efficacy. In this work,
      analogs of our lead compound possessing 2- and 4-aminothiazole rings in place of
      the aminopyridine were synthesized. The less basic aminothiazole rings will be
      less protonated at physiological pH than the aminopyridine ring, and so the
      molecule will carry a lower net charge. This could lead to an increased ability
      to cross the blood-brain barrier thereby increasing the in vivo potency of these
      compounds. The 2-aminothiazole-based compound was less potent than the 2
      aminopyridine-based analogue. 4-Aminothiazoles were unstable in water, undergoing
      tautomerization and hydrolysis to give inactive thiazolones.

PMID- 19590738
TI  - Continuous flow based catch and release protocol for the synthesis of alpha
      ketoesters.
AB  - Using a combination of commercially available mesofluidic flow equipment and
      tubes packed with immobilised reagents and scavengers, a new synthesis of alpha
      ketoesters is reported.

PMID- 19590741
TI  - From discovery to production: scale-out of continuous flow meso reactors.
AB  - A continuous flow parallel reactor system has been developed to provide a rapid
      and seamless transition from the discovery phase and production phase of chemical
      synthesis, particularly in low volume-high value pharmaceuticals production.
      Using a single fixed bed catalytic meso reactor, reactions can be screened on a
      small discovery scale over short time scales. The intensified process produces
      sufficient material for a full analysis. By replication of the single reactor in
      parallel, the same chemistry can be achieved on a larger scale, on a small
      footprint and without the mass and heat transport limitations of reactor scale
      out in batch.

PMID- 19590742
TI  - Behavioral Comorbidities in Rheumatoid Arthritis: A Psychoneuroimmunological
      Perspective.

PMID- 19590743
TI  - Controlling hazardous chemicals in microreactors: synthesis with iodine azide.
AB  - Aromatic aldehydes have been converted into the corresponding carbamoyl azides
      using iodine azide. These reactions have been performed safely under continuous
      flow reaction conditions in microreactors.

PMID- 19590744
TI  - The development and evaluation of a continuous flow process for the lipase
      mediated oxidation of alkenes.
AB  - We report the use of an immobilised form of Candida antarctica lipase B,
      Novozym((R)) 435, in a preliminary investigation into the development of a
      continuous flow reactor capable of performing the chemo-enzymatic oxidation of
      alkenes in high yield and purity, utilising the commercially available oxidant
      hydrogen peroxide (100 volumes). Initial investigations focussed on the lipase
      mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions
      subsequently employed for the epoxidation of an array of aromatic and aliphatic
      alkenes in 97.6 to 99.5% yield and quantitative purity.

PMID- 19590745
TI  - Synthesis of rigidified flavin-guanidinium ion conjugates and investigation of
      their photocatalytic properties.
AB  - Flavin chromophores can mediate redox reactions upon irradiation by blue light.
      In an attempt to increase their catalytic efficacy, flavin derivatives bearing a
      guanidinium ion as oxoanion binding site were prepared. Chromophore and substrate
      binding site are linked by a rigid Kemp's acid structure. The molecular structure
      of the new flavins was confirmed by an X-ray structure analysis and their
      photocatalytic activity was investigated in benzyl ester cleavage, nitroarene
      reduction and a Diels-Alder reaction. The modified flavins photocatalyze the
      reactions, but the introduced substrate binding site does not enhance their
      performance.

PMID- 19590746
TI  - EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS.
AB  - The determination of external dose to teeth of inhabitants of settlements near
      the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry
      technique to assess radiation doses associated with exposure to radioactive
      fallout from the test site. In this study, tooth doses have been reconstructed
      for 103 persons with all studied teeth having been formed before the first
      nuclear test in 1949. Doses above those received from natural background
      radiation, termed "accident doses", were found to lie in the range from zero to
      approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk
      city was approximately 9 Gy. The variability of reconstructed doses within each
      of the settlements demonstrated heterogeneity of the deposited fallout as well as
      variations in lifestyle. The village mean external gamma doses for residents of
      nine[ settlements were in the range from a few tens of mGy to approximately 100
      mGy.

PMID- 19590747
TI  - Ruthenium Vinyl Carbene Intermediates in Enyne Metathesis.
AB  - This review provides an overview of ruthenium vinyl carbene reactivity as it
      relates to enyne metathesis. Methods for the synthesis of metathesis-active and
      metathesis-inactive complexes are also summarized. Some of the early hypotheses
      about vinyl carbene intermediates in enyne metatheses were tested in the arena of
      synthetic chemistry and subsequently led to mechanistic studies. In these two
      areas, studies from the author's labs are described. There are still many
      unresolved questions in enyne metathesis that trace back to vinyl carbene
      reactivity. Hopefully this review will stimulate further investigation into vinyl
      carbene reactivity which should further refine our understanding of catalytic
      enyne metathesis.

PMID- 19590748
TI  - A comprehensive bioinformatics analysis of the Nudix superfamily in Arabidopsis
      thaliana.
AB  - Nudix enzymes are a superfamily with a conserved common reaction mechanism that
      provides the capacity for the hydrolysis of a broad spectrum of metabolites. We
      used hidden Markov models based on Nudix sequences from the PFAM and PROSITE
      databases to identify Nudix hydrolases encoded by the Arabidopsis genome. 25
      Nudix hydrolases were identified and classified into 11 individual families by
      pairwise sequence alignments. Intron phases were strikingly conserved in each
      family. Phylogenetic analysis showed that all multimember families formed
      monophyletic clusters. Conserved familial sequence motifs were identified with
      the MEME motif analysis algorithm. One motif (motif 4) was found in three diverse
      families. All proteins containing motif 4 demonstrated a degree of preference for
      substrates containing an ADP moiety. We conclude that HMM model-based genome
      scanning and MEME motif analysis, respectively, can significantly improve the
      identification and assignment of function of new members of this mechanistically
      diverse protein superfamily.

PMID- 19590749
TI  - Polyionic polymers--heterogeneous media for metal nanoparticles as catalyst in
      Suzuki-Miyaura and Heck-Mizoroki reactions under flow conditions.
AB  - The preparation of monolithic polyionic supports which serve as efficient
      heterogeneous supports for palladium(0) nanoparticles is described. These
      functionalized polymers were incorporated inside a flow reactor and employed in
      Suzuki-Miyaura and Heck cross couplings under continuous flow conditions.

PMID- 19590750
TI  - Synthesis of novel photochromic pyrans via palladium-mediated reactions.
AB  - Photochromic pyrans for applications in material and life sciences were
      synthesized via palladium-mediated cyanation, carbonylation and Sonogashira cross
      coupling starting from bromo-substituted naphthopyran 1 and benzopyrans 2a/b. A
      novel photoswitchable benzopyran-based omega-amino acid 6 for Fmoc-based solid
      phase peptide synthesis is presented. The photochromic behaviour of the 3-cyano
      substituted benzopyran 5a was investigated by time-resolved absorption
      spectroscopy in the picosecond time domain.

PMID- 19590751
TI  - Using Microfluidics to Decouple Nucleation and Growth of Protein Crystals.
AB  - A high throughput, low volume microfluidic device has been designed to decouple
      the physical processes of protein crystal nucleation and growth. This device,
      called the Phase Chip, is constructed out of poly(dimethylsiloxane) (PDMS)
      elastomer. One of the Phase Chip's innovations is to exploit surface tension
      forces to guide each drop to a storage chamber. We demonstrate that nanoliter
      water-in-oil drops of protein solutions can be rapidly stored in individual wells
      thereby allowing the screening of 1000 conditions while consuming a total of only
      10 mug protein on a 20 cm(2) chip. Another significant advance over current
      microfluidic devices is that each well is in contact with a reservoir via a
      dialysis membrane through which only water and other low molecular weight organic
      solvents can pass, but not salt, polymer, or protein. This enables the
      concentration of all solutes in a solution to be reversibly, rapidly, and
      precisely varied in contrast to current methods, such as the free interface
      diffusion or sitting drop methods, which are irreversible. The Phase Chip
      operates by first optimizing conditions for nucleation by using dialysis to
      supersaturate the protein solution, which leads to nucleation of many small
      crystals. Next, conditions are optimized for crystal growth by using dialysis to
      reduce the protein and precipitant concentrations, which leads small crystals to
      dissolve while simultaneously causing only the largest ones to grow, ultimately
      resulting in the transformation of many small, unusable crystals into a few large
      ones.

PMID- 19590753
TI  - Maternally derived Cu tolerance in larval fathead minnows: how long does it
      persist?
AB  - Fathead minnow Pimephales promelas larvae were produced by either copper (Cu)
      exposed or naive females and then subjected to a 96 h survival test using Cu
      concentrations of 400 and 800 microg l(-1). Three survival challenges were
      conducted: the first survival test featured 0 day-old larvae while the second and
      third featured 8 and 15 day-old larvae, respectively. The results of this study
      show that maternally derived Cu tolerance was relatively short-lived as it
      persisted for <8 days.

PMID- 19590752
TI  - Rab4b is a small GTPase involved in the control of the glucose transporter GLUT4
      localization in adipocyte.
AB  - BACKGROUND: Endosomal small GTPases of the Rab family, among them Rab4a, play an
      essential role in the control of the glucose transporter GLUT4 trafficking, which
      is essential for insulin-mediated glucose uptake. We found that adipocytes also
      expressed Rab4b and we observed a consistent decrease in the expression of Rab4b
      mRNA in human and mice adipose tissue in obese diabetic states. These results led
      us to study this poorly characterized Rab member and its potential role in
      glucose transport. METHODOLOGY/PRINCIPAL FINDINGS: We used 3T3-L1 adipocytes to
      study by imaging approaches the localization of Rab4b and to determine the
      consequence of its down regulation on glucose uptake and endogenous GLUT4
      location. We found that Rab4b was localized in endosomal structures in
      preadipocytes whereas in adipocytes it was localized in GLUT4 and in VAMP2
      positive compartments, and also in endosomal compartments containing the
      transferrin receptor (TfR). When Rab4b expression was decreased with specific
      siRNAs by two fold, an extent similar to its decrease in obese diabetic subjects,
      we observed a small increase (25%) in basal deoxyglucose uptake and a more
      sustained increase (40%) in presence of submaximal and maximal insulin
      concentrations. This increase occurred without any change in GLUT4 and GLUT1
      expression levels and in the insulin signaling pathways. Concomitantly, GLUT4 but
      not TfR amounts were increased at the plasma membrane of basal and insulin
      stimulated adipocytes. GLUT4 seemed to be targeted towards its non-endosomal
      sequestration compartment. CONCLUSION/SIGNIFICANCE: Taken our results together,
      we conclude that Rab4b is a new important player in the control of GLUT4
      trafficking in adipocytes and speculate that difference in its expression in
      obese diabetic states could act as a compensatory effect to minimize the glucose
      transport defect in their adipocytes.

PMID- 19590754
TI  - Effects of stimulus font and size on masked repetition priming: An event-related
      potentials (ERP) investigation.
AB  - The size and font of target words were manipulated in a masked repetition priming
      paradigm with ERP recordings. Repetition priming effects were found in four ERP
      components: the N/P150, N250, P325, and N400. Neither a change in font nor a
      change in size across prime and target were found to affect repetition priming in
      the N250, P325, and N400 components. Changing font was, however, found to affect
      repetition priming in the N/P150 component, while the interaction between
      repetition priming and size was not significant in this component. These results
      confirm our interpretation of the N/P150 as a component sensitive to feature
      level processing, and suggest that the type of prelexical and lexical processing
      reflected in the N250, P325, and N400 components is performed on representations
      that are invariant to changes in both font and size.

PMID- 19590755
TI  - Effects of pulsatile subcutaneous injections of insulin lispro on plasma insulin
      concentration levels.
AB  - BACKGROUND: Most insulin pumps used for the treatment of diabetes perform
      subcutaneous insulin injections by pulses. The purpose of this work is to analyze
      the effects of pulsatile injections of modern insulins on plasma insulin levels
      compared with a continuous insulin infusion. METHOD: We simulate pulsatile
      implementations of a basal rate profile over a day on a type 1 diabetes mellitus
      patient using insulin lispro. Pulse periods were varied between 1 and 60 min, and
      random pump errors were included, modeled as white noise, 1/f noise, or 1/f(2)
      noise with relative standard deviations up to 10% of the pump output. RESULTS:
      Oscillations in plasma insulin caused by the pulsatile injections were not
      significant with respect to the global variations for pulse periods below 15 min.
      This cutoff period was found to be robust to random pump errors with standard
      deviations up to 10% of the pump output and hence solely determined by the
      insulin kinetics. Additionally, we showed that the pulse period achieving the
      best implementation of a continuous profile is an increasing function of the
      error variance for a given type of noise. CONCLUSIONS: Our findings support that
      continuous insulin infusion can be implemented by a pulsatile injection of
      insulin as infrequent as a pulse every 15 min without significant effects on
      plasma insulin levels. If clinically confirmed, this result would have important
      consequences on the design and in silico testing of automated insulin treatment
      strategies, as increased delivery intervals imply higher accuracy of insulin
      delivery and facilitated implementations of closed-loop control algorithms.

PMID- 19590757
TI  - Council of Europe actions to promote the rights and full inclusion of ageing
      people with disabilities.

PMID- 19590758
TI  - Bridging knowledge in long-term care and support. Crossing boundaries between
      ageing and disability.

PMID- 19590759
TI  - Preface.

PMID- 19590756
TI  - Expression and potential role of major inflammatory cytokines in experimental
      keratomycosis.
AB  - PURPOSE: The aim of this study was to investigate the expression and regulation
      of the four major inflammatory cytokines in fungal keratitis (FK) with the goal
      of further understanding its pathogenesis in order to develop more effective
      therapeutic approaches. METHODS: Aspergillus fumigatus and Candida albicans were
      the corneal pathogens selected for this study to establish murine FK using
      epikeratophakia with the aid of corneal epithelium erasion. One, three, five, and
      seven days post-infection, the corneal lesions and inflammatory responses were
      observed by slit-lamp and histopathology, and the expressions of the four
      inflammatory cytokines, macrophage inflammatory protein-2 (MIP-2), cytokine
      induced neutrophil chemoattractant (KC), interleukin-1beta (IL-1beta), and
      interleukin-6 (IL-6), in the infected corneas were determined using reverse
      transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA). For the intervention experiment with neutralizing antibodies, the
      experimental mice were then injected subconjunctivally with 5 microl (2
      ng/microl) MIP-2 or IL-1beta polyclonal antibody 1 h before and 24 h after
      surgery. Reestablishment of the FK murine model was performed following
      injection. Effects of MIP-2 or IL-1beta polyclonal antibody on the corneal
      diseases were observed by slit-lamp microscopy, histopathology, and ELISA.
      RESULTS: Expression of MIP-2, KC, IL-1beta, and IL-6 was upregulated
      significantly in the infected group one, three, five, and seven days after
      surgery. Following treatment with an MIP-2 polyclonal antibody, the corneal
      clinical scores and inflammatory responses decreased, the MIP-2 protein levels
      were downregulated significantly (p<0.01), and the KC protein levels decreased
      slightly (p>0.05). Upon administration of IL-1beta polyclonal antibodies, the
      decrease in clinical scores, inflammatory responses, and protein levels of MIP-2
      and KC was apparent at 1 and 3 days after infection (p<0.01). CONCLUSIONS: A
      persistent, high level expression of MIP-2 and IL-1beta is an important and even
      major factor in the corneal pathogenesis of FK. Specific polyclonal neutralizing
      antibodies may be administered to inhibit the major chemokines and cytokines
      responsible for corneal damage thus effectively relieving the injury caused by
      FK.

PMID- 19590760
TI  - Bridging knowledge: reflections on crossing the boundaries between long-term care
      and support.
AB  - In March 2009 members of the research, policy and practice communities in the
      fields of ageing and disability came together in Barcelona for the first
      international conference on bridging knowledge in long-term care and support.
      This paper presents a brief snapshot of some of the key themes and ideas that
      emerged during three days of presentation and debate on methods, policy and
      practice.

PMID- 19590761
TI  - The Depression Initiative. Description of a collaborative care model for
      depression and of the factors influencing its implementation in the primary care
      setting in the Netherlands.
AB  - BACKGROUND: In the Depression Initiative, a promising collaborative care model
      for depression that was developed in the US was adapted for implementation in the
      Netherlands. AIM: Description of a collaborative care model for major depressive
      disorder (MDD) and of the factors influencing its implementation in the primary
      care setting in the Netherlands. DATA SOURCES: Data collected during the
      preparation phase of the CC:DIP trial of the Depression Initiative, literature,
      policy documents, information sheets from professional associations. RESULTS:
      Factors facilitating the implementation of the collaborative care model are
      continuous supervision of the care managers by the consultant psychiatrist and
      the trainers, a supportive web-based tracking system and the new reimbursement
      system that allows for introduction of a mental health care-practice nurse (MHC
      PN) in the general practices and coverage of the treatment costs. Impeding
      factors might be the relatively high percentage of solo-primary care practices,
      the small percentage of professionals that are located in the same building,
      unfamiliarity with the concept of collaboration as required for collaborative
      care, the reimbursement system that demands regular negotiations between each
      health care provider and the insurance companies and the reluctance general
      practitioners might feel to expand their responsibility for their depressed
      patients. CONCLUSION: Implementation of the collaborative care model in the
      Netherlands requires extensive training and supervision on micro level,
      facilitation of reimbursement on meso- and macro level and structural effort to
      change the treatment culture for chronic mental disorders in the primary care
      setting.

PMID- 19590766
TI  - Triggering cryptic natural product biosynthesis in microorganisms.
AB  - Natural products from microorganisms are a crucial source for novel therapeutics.
      Even so, it seems that many valuable compounds are overlooked when culturing
      microbes under standardized laboratory conditions. Many biosynthesis genes remain
      silent and such "cryptic" or "orphan" pathways are only activated under specific
      conditions. This report gives an overview on the strategies to trigger
      biosynthetic pathways to yield "cryptic natural products" through external cues,
      co-cultivation and genomic approaches such as genome-mining, epigenetic
      remodeling, and engineered pathway activation.

PMID- 19590762
TI  - Health systems integration: state of the evidence.
AB  - INTRODUCTION: Integrated health systems are considered a solution to the
      challenge of maintaining the accessibility and integrity of healthcare in
      numerous jurisdictions worldwide. However, decision makers in a Canadian health
      region indicated they were challenged to find evidence-based information to
      assist with the planning and implementation of integrated healthcare systems.
      METHODS: A systematic literature review of peer-reviewed literature from health
      sciences and business databases, and targeted grey literature sources. RESULTS:
      Despite the large number of articles discussing integration, significant gaps in
      the research literature exist. There was a lack of high quality, empirical
      studies providing evidence on how health systems can improve service delivery and
      population health. No universal definition or concept of integration was found
      and multiple integration models from both the healthcare and business literature
      were proposed in the literature. The review also revealed a lack of standardized,
      validated tools that have been systematically used to evaluate integration
      outcomes. This makes measuring and comparing the impact of integration on system,
      provider and patient level challenging. DISCUSSION AND CONCLUSION: Healthcare is
      likely too complex for a one-size-fits-all integration solution. It is important
      for decision makers and planners to choose a set of complementary models,
      structures and processes to create an integrated health system that fits the
      needs of the population across the continuum of care. However, in order to have
      evidence available, decision makers and planners should include evaluation for
      accountability purposes and to ensure a better understanding of the effectiveness
      and impact of health systems integration.

PMID- 19590767
TI  - Creative approaches towards the synthesis of 2,5-dihydro- furans, thiophenes, and
      pyrroles. One method does not fit all!
AB  - A single method is never sufficient, which is why there is a great need for
      developing many diverse and creative approaches towards every chemical substrate
      class. This statement is supported by the contents of this perspective in
      addition to providing the reader with a helpful synthetic roadmap for selecting a
      suitable method for the building blocks being discussed. Detailed in this review
      are eight different synthetic approaches that provide access to valuable 2,5
      dihydro- furan, thiophene and pyrrole building blocks. Each approach is briefly
      presented and its limits discussed. The strengths and weaknesses of each approach
      are further highlighted with a graphical table summary at the end. This summary
      clearly drives home the point that for every chemical substrate class we need
      many good methods in order to provide access to every member of each class.

PMID- 19590768
TI  - Highly stereoselective synthesis of (Z,E)-1-halo-1,3-dienol esters via
      rearrangement of Fischer chromium chloro-carbenes using microwave irradiation.
AB  - Functionalized (Z,E)-1-halo-1,3-dienol esters are synthesized in a highly
      stereoselective manner via CrCl2-mediated rearrangement of allylic
      trihalomethylcarbinol esters induced by microwave irradiation.

PMID- 19590769
TI  - Triflic imide-catalyzed cascade cycloaddition and Friedel-Crafts reaction of
      diarylvinylidenecyclopropanes with ethyl 5,5-diarylpenta-2,3,4-trienoate.
AB  - Triflic imide-catalyzed cascade cycloaddition and Friedel-Crafts reaction of
      diarylvinylidenecyclopropanes with ethyl 5,5-diarylpenta-2,3,4-trienoates
      provided a variety of novel polycyclic ester derivatives in moderate to good
      yields under mild conditions.

PMID- 19590770
TI  - Enzymatic synthesis of sialylation substrates powered by a novel polyphosphate
      kinase (PPK3).
AB  - Active inclusion bodies of polyphosphate kinase 3 and cytidine 5'-monophosphate
      kinase were combined with whole cells that co-express sialic acid aldolase and
      CMP-sialic acid synthetase. The biocatalytic mixture was used for the synthesis
      of CMP-sialic acid, which was then converted to 3'-sialyllactose by whole cells.

PMID- 19590771
TI  - Fluorescent carbazolylurea anion receptors.
AB  - A series of fluorescent carbazolylurea base anion receptors have been synthesised
      that show a high affinity for oxo-anions (particularly bicarbonate and acetate).
      The fluorescence of dicarbazolylurea (1) is quenched upon addition of benzoate
      anions in DMSO-0.5% water.

PMID- 19590773
TI  - Functionalization of 2'-amino-LNA with additional nucleobases.
AB  - Thymin-1-yl-acetic acid and adenin-9-yl-acetic acid have been coupled to the N2'
      atom of a 2'-amino-LNA thymine nucleoside, and these "double-headed" LNA monomers
      have been incorporated into oligodeoxyribonucleotides via their corresponding
      phosphoramidite derivatives. Oligonucleotides containing these modified
      nucleotides show in most cases increased thermal stability when forming duplexes
      with complementary DNA, even allowing multiple incorporations. Incorporation of
      "double-headed" LNA monomers in both strands also led to stable duplexes,
      however, no indication of Watson-Crick base pairing between the extra nucleobases
      could be found.

PMID- 19590772
TI  - Colorful methods to detect ion channels and pores: intravesicular chromogenic
      probes that respond to pH, pM and covalent capture.
AB  - The activity of synthetic pores, ion channels, transporters and carriers is
      usually determined with fluorescent probes in vesicles or by conductance
      measurements in planar lipid bilayers. Elaborating on more colorful alternatives,
      we here introduce 5(6)-carboxynaphthofluorescein (CNF) as an intravesicular pH
      probe for the colorimetric detection of activity, selectivity and cooperativity
      of ion channels such as gramicidin A. We further report that intravesicular
      pyrocatechol violet (PV), together with extravesicular Cu2+, extravesicular 4
      carboxyphenylboronic acid (CBA) or intravesicular 4-(benzyl-N-glutamate)boronic
      acid (BGBA) can detect the activity of synthetic pores or cell-penetrating
      peptide (CPP) sensors. Their response to analytes such as dodecylphosphate,
      hyaluronan or IP6 are reported as high-contrast color changes from yellow to
      blue, from yellow to red, or from red to green.

PMID- 19590774
TI  - Interactions of vinca alkaloid subunits with chiral amido[4]resorcinarenes: a
      dynamic, kinetic, and spectroscopic study.
AB  - The stereoselectivity of the reaction between (R)-(-)-2-butylamine and the
      diastereomeric proton-bound complexes of (+)-catharanthine (C) or (-)-vindoline
      (V) with some chiral amido[4]resorcinarenes has been investigated in the gas
      phase by ESI-FT-ICR-MS. The reaction stereoselectivity (0.56 < k(homo)/k(hetero)
      < 16.9) is found to depend critically on the functional groups present in the
      chiral pendants of the hosts. Rationalisation of the kinetic results is based on
      careful computational and spectroscopic studies of the most stable conformations
      of (+)-catharanthine and its protonated form in the isolated state and in water,
      as well as in a representative host structure. The emerging picture points to the
      relevant diastereomeric proton-bound complexes as quasi-degenerate, thus
      suggesting that their stereoselectivity in the guest exchange reaction is mostly
      due to kinetic factors. The results of this study may represent a starting point
      for a deeper comprehension of the intrinsic factors that endow these molecules,
      and their dimeric forms, with their biochemical properties.

PMID- 19590775
TI  - A theoretical study on the mechanism of the base-promoted decomposition of N
      chloro,N-methylethanolamine.
AB  - The first step of the base-promoted decomposition of N-chloro,N
      methylethanolamine in aqueous solution (CH3N(Cl)CH2CH2OH + HO- --> imine + Cl- +
      H2O (+ CH2O) --> amine + aldehyde) is investigated at the MP2/6-31++G(d,p)
      computing level. Solvation is included by using both a microsolvated model, in
      which two explicit water molecules simulate the specific solvent effects, and a
      hybrid cluster-continuum model, by applying a polarized continuum on the previous
      results, to account for the bulk effect of the solvent. Four alternative pathways
      (bimolecular fragmentation, Hofmann, Zaitsev and intramolecular eliminations) are
      possible for the rate-limiting step of this base-promoted decomposition. These
      reactive processes are bimolecular asynchronous concerted reactions. The common
      feature of the four pathways is the proton transfer to HO- being more advanced
      than all other molecular events, whereas imine formation is delayed. Non-reactive
      cyclic arrangements involving one of the explicit water molecules are found at
      transition structures of Hofmann and Zaitsev eliminations, such water molecule
      acting both as H+ donor and acceptor. Although MP2 calculations misjudge the
      absolute activation Gibbs free energy values, this computational level adequately
      predicts the enhancement in the decomposition rate due to the presence of the -OH
      group.

PMID- 19590776
TI  - Refined multivalent display of bacterial spore-binding peptides.
AB  - A multiple antigen peptide display scaffold was used to create multivalent
      versions of a heptapeptide selected previously by phage display to bind to
      Bacillus subtilis spores. A simple flow cytometric assay was developed in which a
      biotinylated form of the peptide was first bound to fluorescent streptavidin,
      then the fluorescent streptavidin-peptide complex was bound to spores before
      introduction into the cytometer. This assay clearly demonstrated that the
      tetravalent scaffold enhanced the affinity for B. subtilis spores by greater than
      1 and 2 orders of magnitude when compared to divalent and monovalent analogues,
      respectively. However, variations in the number and flexibility of spacer
      residues within the scaffold did not significantly affect the binding affinity of
      the tetravalent peptides. Similar to prior reports, these multivalent scaffolds
      are effective most likely because they mimic the multivalent display of the
      original peptide library on the phage coat. Moreover, the tetravalent peptides
      can be readily integrated into a variety of heterogeneous and homogeneous spore
      detection assay formats.

PMID- 19590777
TI  - High-throughput synthesis of azide libraries suitable for direct "click"
      chemistry and in situ screening.
AB  - A key challenge in current drug discovery is the development of high-throughput
      (HT) amenable chemical reactions that allow rapid synthesis of diverse chemical
      libraries of enzyme inhibitors. The Cu(I)-catalyzed, 1,3-dipolar cycloaddition
      between an azide and an alkyne, better known as "click chemistry", is one such
      method that has received the most attention in recent years. Despite its
      popularity, there is still a lack of robust and efficient chemical strategies
      that give access to diverse libraries of azide-containing building blocks (key
      components in click chemistry). We report herein a highly robust and efficient
      strategy for high-throughput synthesis of a 325-member azide library. The method
      is highlighted by its simplicity and product purity. The utility of the library
      is demonstrated with the subsequent "click" synthesis of the corresponding
      bidentate inhibitors against PTP1B.

PMID- 19590778
TI  - Diversity oriented syntheses of fused pyrimidines designed as potential
      antifolates.
AB  - Diversity oriented syntheses of some furo[2,3-d]pyrimidines and pyrrolo[2,3
      d]pyrimidines related to folate, guanine, and diaminopyrimidine-containing drugs
      have been developed for the preparation of potential anti-infective and
      anticancer compounds. Amide couplings and Suzuki couplings on the basic
      heterocyclic templates were used, in the latter case yields being especially high
      using aromatic trifluoroborates as the coupling partner. A new ring synthesis of
      6-aryl-substituted deazaguanines bearing 2-alkylthio groups has been developed
      using Michael addition of substituted nitrostyrenes. Diversity at C-2 has been
      introduced by oxidation and substitution with a range of amino nucleophiles. The
      chemical reactivity of these pyrrolopyrimidines with respect to both
      electrophilic substitution in ring synthesis and nucleophilic substitution for
      diversity is discussed. Several compounds were found to inhibit pteridine
      reductases from the protozoan parasites Trypanosoma brucei and Leishmania major
      at the micromolar level and to inhibit the growth of Trypanosma brucei brucei in
      cell culture at higher concentrations. From these results, significant structural
      features required for inhibition of this important drug target enzyme have been
      identified.

PMID- 19590780
TI  - Reaction of [60]fullerene with trans-epoxides: a theoretical study.
AB  - The experimental results of the reaction of C60 with carbonyl ylides generated
      from trans-epoxides, which afforded cis-products exclusively or predominantly,
      can be explained well by computational investigation of the proposed reaction
      mechanism. Our theoretical calculations demonstrate that only cis-carbonyl ylides
      can be formed directly from trans-epoxides, in compliance with the Woodward
      Hoffmann rule. Importantly, the ring opening of trans-epoxides, which is the rate
      determining step, should be included in the whole reaction profiles to explain
      all experimental phenomena.

PMID- 19590779
TI  - A new synthesis of alkene-containing minor-groove binders and essential hydrogen
      bonding in binding to DNA and in antibacterial activity.
AB  - A practical synthesis of alkene-containing minor-groove binders for DNA, related
      to distamycin, with potential for wide structural diversity is described, based
      upon the Wittig chemistry of N-alkylpyrrole aldehydes. The compounds prepared
      have been evaluated for binding to DNA by physical methods (melting temperature
      and NMR) and for their antibacterial activity. Significantly, it was found that
      alkenes linking the aryl head group of the minor-groove binder promote strong
      binding to DNA and high antibacterial activity against Gram-positive bacteria.
      Conversely, a minor-groove binder containing an alkene located towards the
      alkylamino tail group has a low affinity for DNA and does not show antibacterial
      activity. These observations suggest an important role for specific hydrogen
      bonds in the binding of compounds of this type to DNA, and in their antibacterial
      activity.

PMID- 19590781
TI  - Application of Nazarov cyclization to access [6-5-6] and [6-5-5]tricyclic core
      embedded new heterocycles: an easy entry to structures related to
      taiwaniaquinoids.
AB  - A concise and general route to synthesize a new class of [6-5-6] tricyclic core
      embedded polyheterocycles has been accomplished using diastereoselective Nazarov
      cyclization with an overall yield of 35-40%. Versatility of this synthetic route
      has also been demonstrated by accessing a variety of [6-5-5] tricyclic core
      incorporated polycycles. It was observed that the efficiency of cyclization
      depends upon the impact of polarization on the reacting systems. Amongst the
      various Lewis and Bronsted acids screened for cyclization, triflic acid was found
      to be the most effective catalyst.

PMID- 19590782
TI  - Three-dimensional structure-activity relationship study of belactosin A and its
      stereo- and regioisomers: development of potent proteasome inhibitors by a
      stereochemical diversity-oriented strategy.
AB  - The development of potent proteasome inhibitors based on the stereochemical
      diversity-oriented strategy using a conformationally rigid cyclopropane structure
      was investigated. Thus, a series of stereo- and regioisomeric analogs of
      belactosin A (2), a cyclopropane amino acid (methanoamino acid)-containing
      tripeptidic proteasome inhibitor, were designed, in which the central
      cyclopropane amino acid part was replaced with the corresponding stereo- or
      regioisomer. Using a series of stereoisomeric cyclopropane amino acid equivalents
      with the cis/trans, D/L, and syn/anti stereochemical diversity, which were
      previously developed by us, as key units, the target compounds were successfully
      synthesized. Biological evaluation showed that, as expected, compound activity
      changed depending on the stereochemistry of the central cyclopropane amino acid
      part: the trans/L-syn-isomer 7 and the cis/L-anti-isomer 9 were more than twice
      as potent as natural belactosin A (trans/L-anti-isomer). Furthermore, the
      tripeptidic compound 13, the synthetic precursor for the unnatural cis/L-anti
      isomer 9, was identified as a highly potent proteasome inhibitor. This compound,
      which is 20 times as potent as belactosin A and is even more potent than the well
      known inhibitor lactacystin (4), may be an effective lead for developing
      clinically useful anticancer drugs. These results show that the stereochemical
      diversity-oriented approach can be a powerful strategy for the development of
      highly active compounds in medicinal chemical studies.

PMID- 19590783
TI  - Organocatalysts immobilised onto gold nanoparticles: application in the
      asymmetric reduction of imines with trichlorosilane.
AB  - Gold nanoparticles functionalised with a valine-derived formamide have been
      developed as effective homogenous catalysts for the asymmetric reduction of
      ketimine 1 with trichlorosilane (< or = 84% ee) in toluene. This methodology both
      simplifies the recovery of the catalyst and its separation from the product, as
      the nanoparticles can be readily removed and subsequently recycled by
      precipitation from the reaction mixture.

PMID- 19590784
TI  - Evaluation of fluorescent polysaccharide nanoparticles for pH-sensing.
AB  - The comprehensive characterization of novel dextran nanoparticles with regard to
      their suitability as pH-sensors for analytical applications (e.g. in physiology)
      is described. The nanoparticles are labeled with both a pH-indicator dye
      (fluorescein isothiocyanate, FITC) and a reference dye (sulforhodamine B acid
      chloride) as an internal standard. The fluorescence intensity of FITC increases
      with increasing pH, whereas the signal of the reference dye remains constant.
      Plotting the ratio of both signals against the pH gives a pK(a) of 6.45, which is
      appropriate for most of the measurement purposes. Furthermore, the influence of
      temperature, ionic strength and oxidizing substances on the performance of the
      fluorophores inside the dextran nanoparticles is examined. These results are
      compared to the dissolved dyes in order to evaluate if the dextran matrix affects
      the fluorescence properties of the sensor and the reference dye, and whether or
      not these nanosensors are suitable for pH-sensing in biological samples.

PMID- 19590785
TI  - Supramolecular chiral dendritic monophosphites assembled by hydrogen bonding and
      their use in the Rh-catalyzed asymmetric hydrogenation.
AB  - A new type of supramolecular chiral dendritic monophosphite ligands has been
      prepared via a hydrogen-bonding assembly. The Rh complexes of these
      supramolecular ligands have been successfully applied in the asymmetric
      hydrogenation of enamides and dehydroamino acid derivatives with good
      enantioselectivities, which are comparable to those obtained from the free
      monophosphite ligands. The supramolecular catalyst could be easily recycled via
      solvent precipitation.

PMID- 19590786
TI  - Towards a molecular-level understanding of the reactivity differences for radical
      anions of juglone and plumbagin: an electrochemical and spectroelectrochemical
      approach.
AB  - An electrochemical and spectroelectrochemical strategy is presented for
      evaluating reactivity differences in the semiquinone anions from naturally
      occurring quinones juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (2-methyl
      5-hydroxy-1,4-naphthoquinone). By employing cyclic voltammetry and in situ
      spectroelectrochemical electron spin resonance measurements, it was found that
      while semiquinone species generated from plumbagin are stable radical anions in
      DMSO solution, the species generated from juglone are more reactive. These latter
      species are involved in a self-protonation process involving a slow rate of
      protonation (1.8-2.1 mol L(-1)) due to the mild acidity of the OH group at the C
      5 position. This result is important when considering observed differences in
      biochemical reactivity for these quinones, particularly in cases where mediated
      cytotoxic action is provoked by these agents, as is discussed in this work.

PMID- 19590787
TI  - Studies on the hydrolytic stability of 2'-fluoroarabinonucleic acid (2'F-ANA).
AB  - The stability of 2'-deoxy-2'-fluoroarabinonucleic acid (2'F-ANA) to hydrolysis
      under acidic and basic conditions was compared to that of DNA, RNA and 2'F-RNA.
      In enzyme-free simulated gastric fluid (pH approximately 1.2), 2'F-ANA was found
      to have dramatically increased stability (virtually no cleavage observed after 2
      days) with respect to both DNA (t(1/2) approximately 2 min) and RNA (t(1/2)
      approximately 3 h (PO) or 3 days (PS)). These results were observed for both
      phosphodiester and phosphorothioate backbones and with multiple mixed-base
      sequences. Under basic conditions, 2'F-ANA also showed good stability. In 1 M
      NaOH at 65 degrees C, 2'F-ANA had a t(1/2) of approximately 20 h, while RNA was
      entirely degraded in a few minutes. Furthermore, the nuclease cleavage of
      phosphorothioate 2'F-ANA and DNA by snake venom phosphodiesterase was studied in
      detail. One diastereomer of the PS-2'F-ANA linkage was found to be much more
      vulnerable to enzymatic cleavage than the other, which is parallel to the
      properties observed for PS-DNA. Additional studies of 2'F-ANA-containing
      oligonucleotides are warranted based on the excellent stability properties
      described here.

PMID- 19590788
TI  - User-friendly stereoselective one-pot access to 1,4-diazepane derivatives by a
      cyclodehydrative three-component reaction with 1,3-dicarbonyls.
AB  - A multicomponent reaction of 1,3-dicarbonyls with 1,2-diamines and aromatic
      aldehydes is described for the direct stereoselective synthesis of 1,4-diazepane
      derivatives. Various reaction conditions were tested, including an efficient,
      user-friendly solvent- and catalyst-free procedure.

PMID- 19590789
TI  - Intramolecular azide-alkyne [3 + 2] cycloaddition: versatile route to new
      heterocyclic structural scaffolds.
AB  - Investigating the relatively unexplored intramolecular version of the azide
      alkyne [3 + 2] cycloaddition, the present studies demonstrate the utility of the
      above reaction in the synthesis of a variety of as yet unreported heterocyclic
      structural scaffolds. The approach involved initial installation of strategic
      azide and alkyne moieties on a common structural framework, followed by their
      intramolecular cycloaddition studies. The pivotal azidoalkyne intermediates were
      efficiently accessed from a variety of easily available starting materials such
      as olefins, epoxides, amino acids, amino alcohols, ketones etc. The key reactions
      for incorporation of the azide functionality into the desired framework involved
      azidolysis of epoxides, displacement of hydroxy groups with azide nucleophiles,
      and diazo transfer on amine. Attachment of the desired alkyne functionalities was
      accomplished by either N-, or, O-alkylation with appropriate propargylic halides.
      The azidoalkynes thus prepared underwent smooth intramolecular cycloaddition,
      resulting in a variety of novel triazolooxazine and triazolopyrazine derivatives.
      Interestingly, unlike in the intermolecular version, metal catalysis was not
      necessary for the performance of the above cycloadditions. It is expected that
      the results from the present studies and its further extension will provide a
      potentially fertile pathway to a variety of unique chemical entities of
      structural and biological significance.

PMID- 19590790
TI  - Synthesis of chromones and 4-hydroxyquinolines based on uncatalyzed condensations
      of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-alkoxy- and 2
      nitrobenzoyl chlorides and related reactions.
AB  - The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2
      methoxybenzoyl chlorides afforded 3,5-diketoesters which were transformed, by
      treatment with boron tribromide, into functionalized 2-hydroxychroman-4-ones or
      chromones. The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene
      with 2-nitrobenzoyl chlorides and subsequent reduction of the nitro group
      afforded functionalized 4-hydroxyquinolines. Their tautomeric equilibrium was
      studied by NMR spectroscopy and by computational methods.

PMID- 19590791
TI  - Macrocyclic aromaticity in Huckel and Mobius conformers of porphyrinoids.
AB  - Macrocyclic aromaticity is one of the key concepts in porphyrin chemistry. The
      degree of macrocyclic aromaticity and the associated main macrocyclic conjugation
      pathway in Huckel- and Mobius-type porphyrinoids were determined using our
      recently proposed procedure based on bond resonance energy (BRE). All
      porphyrinoids with diatropic and paratropic macrocycles were found to have
      positive and negative superaromatic stabilization energies (SSEs), respectively.
      Main macrocyclic conjugation pathways predicted for various porphyrinoids were
      exactly the same as those predicted from the annulene model for porphyrinoids.
      Thus, macrocyclic aromaticity of Huckel and Mobius porphyrinoids has been
      rationalized successfully using an energetic criterion of aromaticity.

PMID- 19590792
TI  - Studies on the biodegradation of fosfomycin: growth of Rhizobium huakuii PMY1 on
      possible intermediates synthesised chemically.
AB  - The first step of the mineralisation of fosfomycin by R. huakuii PMY1 is
      hydrolytic ring opening with the formation of (1R,2R)-1,2
      dihydroxypropylphosphonic acid. This phosphonic acid and its three stereoisomers
      were synthesised by chemical means and tested as their ammonium salts for
      mineralisation as evidenced by release of P(i). Only the (1R,2R)-isomer was
      degraded. A number of salts of phosphonic acids such as (+/-)-1,2-epoxybutyl-,
      (+/-)-1,2-dihydroxyethyl-, 2-oxopropyl-, (S)-2-hydroxypropyl-, (+/-)-1
      hydroxypropyl- and (+/-)-1-hydroxy-2-oxopropylphosphonic acid were synthesised
      chemically, but none supported growth. In vitro C-P bond cleavage activity was
      however detected with the last phosphonic acid. A mechanism involving phosphite
      had to be discarded as it could not be used as a phosphorus source. R. huakuii
      PMY1 grew well on (R)- and (S)-lactic acid and hydroxyacetone, but less well on
      propionic acid and not on acetone or (R)- and (+/-)-1,2-propanediol. The P(i)
      released from (1R,2R)-1,2-dihydroxypropylphosphonic acid labelled with one oxygen
      18 in the PO3H2 group did not stay long enough in the cells to allow complete
      exchange of 18O for 16O by enzymic turnover.

PMID- 19590793
TI  - New insights into the S-nitrosothiol-ascorbate reaction. The formation of
      nitroxyl.
AB  - Although the ascorbate-dependent reduction of S-nitrosothiol to the corresponding
      thiol function is frequently used for analyzing S-nitrosocysteinyl residues in
      proteins, it proceeds with low yields. Our re-investigation of the ascorbate-S
      nitrosothiol reaction demonstrates now the intermediacy of nitroxyl (HNO/3NO-)
      that is highly effective in oxidizing thiols. The occurrence of the HNO reporter
      molecule, i.e., N2O, during and after reaction was unequivocally demonstrated by
      15N NMR. The yield of HNO from the S-nitrosoglutathione-ascorbate reaction was
      determined with the aid of a Mn(III)-complex to 60%, a value that was
      significantly higher than the one of nitric oxide formation (48%) at
      physiological pH. The same HNO yield was observed with a S-nitrosothiol bound to
      a protein (i.e., S-nitroso-papain). With the known chemistry of nitroxyl, it was
      possible to optimize the experimental conditions so that the GSNO-ascorbate
      reaction yielded stoichiometric amounts of glutathione after a reaction period of
      1 min.

PMID- 19590794
TI  - New approaches for the synthesis of erythrinan alkaloids.
AB  - A concise asymmetric total synthesis of (+)-erysotramidine is described, using
      chiral base desymmetrisation of a meso-imide, N-acyliminium addition, retro-Diels
      Alder cycloaddition and radical cyclisation as the key steps. A related route,
      starting from a cyclobutene-fused imide, was explored, and established a novel
      construction of the Erythrina alkaloid skeleton using a key ring-opening/ring
      closing metathesis step. Completion of this synthesis was thwarted by problems
      with the removal of an unwanted vinylic side-chain. Complementary enantiospecific
      routes to Erythrina systems were explored, starting from (L)-malic acid. Some
      unexpected observations were made concerning the diastereocontrol in malic acid
      derived N-acyliminium ion cyclisations, where changing the protecting group of
      the alcohol function from acetate to OTIPS resulted in a dramatic change in
      diastereocontrol. Products from these reactions could be transformed into known
      intermediates for natural alkaloids, and into (+)-demethoxyerythratidinone
      itself, by means of radical cyclisations or intramolecular aldol reactions as the
      key steps.

PMID- 19590795
TI  - Dihydropyridine C-glycoconjugates by organocatalytic Hantzsch cyclocondensation.
      Stereoselective synthesis of alpha-threofuranose C-nucleoside enantiomers.
AB  - The Hantzsch reaction of C-glycosyl aldehyde/enamino ester/beta-ketoester systems
      under l-proline catalysis to give dihydropyridine C-glycoconjugates is reported.
      Asymmetric cyclocondensations of differentially substituted enamine and beta
      dicarbonyl components with formyl alpha-L-C-threofuranoside and with the alpha-D
      isomer were also carried out. Each reaction occurred with high yet opposite
      stereoselectivity (de >95%) so that the pair of alpha-threofuranose C-nucleoside
      enantiomers was prepared.

PMID- 19590806
TI  - Diazinon determination using high performance liquid chromatography: a comparison
      of the ENVI-Carb column with the immunoaffinity column for the pretreatment of
      water and soil samples.
AB  - An immunoaffinity chromatography column was developed to remove diazinon from
      water and soil samples. In this paper, two types of absorbent columns, the
      immunoaffinity chromatography column and the ENVI-Carb column, were compared. To
      accomplish this, each of these columns was used to treat water and soil samples
      that had been spiked with diazinon at concentrations of 2.5 or 5 ng/mL (or ng/g).
      High performance liquid chromatography was then used to analyze the treated
      samples. The ENVI-Carb column recovered 87.99%-95.95% of the diazinon from water
      and soil with CVs of 5.08%-8.06%. The recoveries observed when the immunoaffinity
      chromatography column was used were slightly lower (52.61%-81.58%); however, it
      effectively clean up the soil samples.

PMID- 19590805
TI  - Mental and neurological health research priorities setting in developing
      countries.
AB  - INTRODUCTION: A multi-region consultation process designed to generate locally
      produced regional and global research priorities on mental and neurological
      health in low- and middle-income countries. METHODS: Between 2003 and 2005,
      priority setting exercises on MNH research, using the systematic combined
      approach matrix (CAM) were held in the six regions of the developing world. One
      regional meeting per region was convened, and a global meeting was organized
      before and after the regional exercises. RESULTS: During regional meetings,
      regional agendas were created listing both research priorities and local problems
      in MNH. During global meetings, a global research agenda was established and four
      crucial areas of research priorities were identified: awareness and advocacy,
      enhancement of research capacity, training for service delivery, and development
      of evidence based policy. CONCLUSIONS: The combined matrix approach enabled the
      development of regional and global MNH research agendas, derived from bottom up
      consultations within and between low- and middle-income countries. Collaboration
      between regions with similar priorities was instituted. Such research agendas are
      designed to assist policy-makers and donors in the allocation of scarce
      resources, but they require regular review to reflect changing needs.

PMID- 19590807
TI  - Empirical models to predict parsimoniously the mass and number concentrations of
      ultrafine particulate in ambient atmosphere.
AB  - The main objective of this study was to develop parsimonious empirical models for
      predicting the mass and number concentrations of ultrafine particulate (UFP,
      aerodynamic diameter < 0.1 or 0.18 microm) in the atmospheric environment. We
      found strong correlations existed between the mass/number concentration of UFP
      and the mass concentration of PM(2.5) (aerodynamic diameter < 2.5 microm) by
      fitting the experimental data. Therefore, we were easily able to obtain UFP mass
      and number concentrations by using the presented empirical models. The empirical
      equations should be used with care since limitations existed.

PMID- 19590808
TI  - Alpha emitting radionuclides in drainage from Quinta do Bispo and Cunha Baixa
      uranium mines (Portugal) and associated radiotoxicological risk.
AB  - Two large uranium mines, Quinta do Bispo and Cunha Baixa, district of Viseu,
      North of Portugal, were exploited until 1991. Sulfuric acid was used for in situ
      uranium leaching in Cunha Baixa mine and for heap leaching of low grade ores at
      both mines. Large amounts of mining and milling residues were accumulated nearby.
      Since closure of mines, the treatment of acid mine waters has been maintained and
      treated water is released into surface water lines. Analysis of radionuclides in
      the soluble phase and in the suspended matter of water samples from the uranium
      mines, from the creeks receiving the discharges of mine effluents, from the
      rivers and from wells in this area, show an enhancement of radioactivity levels.
      For example, downstream the discharge of mine effluents into Castelo Stream, the
      concentrations of dissolved uranium isotopes and uranium daughters were up to 14
      times the concentrations measured upstream; (238)U concentration in suspended
      particulate matter of Castelo Stream reached 72 kBq kg(-1), which is about 170
      times higher than background concentrations in Mondego River. Nevertheless,
      radionuclide concentrations decreased rapidly to near background values within a
      distance of about 7 kilometers from the discharge point. Enhancement of
      radioactivity in underground waters was positively correlated with a decrease in
      water pH and with an increase of sulfate ion concentration, pointing out to Cunha
      Baixa mine as the source of groundwater contamination. The radiotoxic exposure
      risk arising from using these well waters as drinking water and as irrigation
      water is discussed and implementation of environmental remediation measures is
      advised.

PMID- 19590809
TI  - Bioweathering and biotransformation of granitic rock minerals by actinomycetes.
AB  - Actinomycetes inhabiting granitic rocks at St. Katherine, Egypt were investigated
      for their bioweathering potential. Actinomycete counts ranged between 174 and 360
      colony forming units per gram. Counts were positively correlated to rock porosity
      (r = 0.65) and negatively correlated to rock salinity (r = -0.56). Sixty-six
      actinomycete isolates originating from rocks could be assigned into eight genera,
      with a high frequency of Nocardioides and Streptomyces. Organic acids were
      produced by 97% of the isolates. Strains belonging to Actinopolyspora,
      Actinomadura, Kitasatospora, Nocardioides, and Kibdelosporangium showed the
      highest acid production indices. Representatives from all eight genera could
      precipitate metals Cu, Fe, Zn, Cd, and Ag up to concentrations of 2.5 mM each. An
      actinomycete consortium of two Nocardioides strains and one Kibdelosporangium
      strain was studied for its potential to cause rock weathering in batch
      experiments. Results indicated a high ability of the consortium to leach the
      metals Cu, Zn, and Fe up to 2.6-, 2.1-, and 1.3-fold, respectively, compared to
      the control after 4 weeks. The pH significantly decreased after 1 week, which was
      parallel to an increased release of phosphate and sulfate reaching a 2.2- and 2.5
      fold increase, respectively, compared to control. Highly significant weight loss
      (p = 0.005) was achieved by the consortium, indicating a potential multiple role
      of actinomycetes in weathering by acid production, metal leaching, and
      solubilization of phosphate and sulfate. This study emphasizes the diverse and
      unique abilities of actinomycetes inhabiting rock surfaces which could be of
      potential biotechnological applications, such as in the bioremediation of metal
      contaminated environments and metal biorecovery.

PMID- 19590810
TI  - Mucobilia: current aspects in the management of a rare cause of malignant biliary
      obstruction.
AB  - Mucobilia is a rare pathologic condition characterized by the abnormal secretion
      and accumulation of abundant mucus within the biliary tree. It is usually seen in
      association with mucin-producing hepatobiliary and pancreatic tumors. Neoplastic
      transformation of these tumors can range from low-grade dysplasia to invasive
      adenocarcinoma. Mucobilia usually presents with signs and symptoms of biliary
      obstruction, which may span from jaundice to cholangitis with progression to
      septic complications in severe cases. Occurrence of hepatolithiasis has also been
      attributed to mucobilia, which raises the concern of an increased risk for the
      development of cholangiocarcinoma. Precise radiological evaluation and detailed
      histopathological tissue diagnosis followed by execution of appropriate surgical
      therapy is vital in the integrated management of mucin-producing biliary
      neoplasms. This review will address the etiologies and symptomatology of
      mucobilia as well as discuss current aspects in the management of mucobilia and
      its causative etiologies.

PMID- 19590811
TI  - Analysis of the helicase gene of Korean swine hepatitis E virus isolates and
      trends in viral infection.
AB  - Hepatitis E virus (HEV) has been considered to be a zoonotic agent and an
      important public concern worldwide. In this study, a nested RT-PCR was developed
      to detect the helicase gene of swine HEV (sHEV) from sera of pigs. Using this RT
      PCR, 16 out of 821 Korean isolates of sHEV were identified, with 1.9% prevalence.
      An age-specific prevalence was demonstrated with the highest prevalence in
      growing pigs (5.4%). Phylogenetic analysis of sHEV Korean isolates identified
      genotype 3, with 89.4-99.9% nucleotide sequence identity. The viruses were
      closely related to US and Japanese HEV isolates from swine and humans (89.4
      93.1%). The prevalence of anti-HEV IgG in individual pigs and swine herds was
      39.5 and 80%, respectively. The seroprevalence rate increased in proportion to
      the age of the swine. The seroprevalence of HEV was higher than previously
      reported. These results indicate that sHEV is widespread in Korean swine herds
      and further raise concerns about possible zoonosis.

PMID- 19590812
TI  - Molecular insights into the phylogeny of canine parvovirus 2 (CPV-2) with
      emphasis on Korean isolates: a Bayesian approach.
AB  - A Bayesian approach was utilized to further investigate the molecular phylogeny
      of canine parvovirus 2 (CPV-2) with emphasis on Korean isolates, and the complete
      VP2 gene sequences for 23 Korean isolates in 2007 and two vaccine strains were
      determined. Of the 44 Korean CPVs, 40 were identified as CPV-2a, three as CPV-2b,
      and the remaining one as a CPV-2a variant having a Gly300Asp mutation. Compared
      with CPV-2a, our findings also showed the presence of six additional amino acid
      substitutions (Thr440Ala, Ile418Thr, Pro435Ser, Asp413Asn, Thr322Ser, and
      Tyr324Ile) within the VP2 gene of the Korean isolates. In the phylogenetic tree,
      the overall Korean CPVs did not emerge as an independent clade within the global
      CPVs, nor did they show a close relationship to the CPVs from any other country.
      Our VP2 sequence data also revealed no geographic influence on the spread of CPVs
      worldwide. dN/dS analysis showed that purifying selection is acting on the VP2
      gene of Korean CPVs.

PMID- 19590814
TI  - Repair of a giant inguinoscrotal hernia.
AB  - Giant inguinoscrotal herniae are infrequent in developed countries nowadays,
      nonetheless they may still typically present after years of neglect. The
      morbidity associated with them can be significant. Surgical management, although
      challenging even for the experienced surgeon, enables the patient to return to a
      reasonable level of function and quality of life. We present a case of a giant
      right inguinoscrotal hernia, which was treated with a multi-stage extensive
      operation, following adequate pre-operative respiratory preparation. The
      operation included reduction of the hernial contents in the abdominal cavity
      following omentectomy, right hemicolectomy and splenectomy, hernioplasty and
      reconstruction of the abdominal wall with the preperitoneal use of a Composix
      mesh and finally reductive reconstruction of the scrotum. The technique described
      represents a successful combination of various techniques described for the
      management of these patients.

PMID- 19590815
TI  - Endometriosis of the groin hernia sac: report of a case and review of the
      literature.
AB  - Endometriosis is characterized by the presence of histological normal endometrial
      tissue outside the uterine cavity. It occurs in up to 15% of menstruating women
      and often goes undetected. Some cases of soft-tissue involvement have been
      reported, particularly in the skin and subjacent tissues of surgical scars.
      However, we came cross a 42-year-old female patient with millimetric focal
      lesions in a groin hernia sac. A case report and a review of the literature are
      presented. Although definitive diagnosis still requires biopsy, the patient's
      cyclic symptoms and history of previous uterine surgery should suggest the
      correct diagnosis.

PMID- 19590816
TI  - Hiatal hernias presenting as a late complication of laparoscopic-assisted cardio
      oesophagectomy.
AB  - The resection of oesophageal cancer offers the only chance of cure. The
      introduction of minimally invasive oesophagectomy has gained wide acceptance for
      the surgical treatment of oesophago-gastric cancers. The most commonly reported
      late complications of minimally invasive oesophagectomy are anastamotic
      stricture, chylothorax, chronic diarrhoea and delayed gastric emptying.
      Symptomatic hiatus hernia presenting as a late complication of laparoscopic
      cardio-oesophagectomy is not a widely reported complication. We have encountered
      three such cases, two of which were treated laparoscopically.

PMID- 19590817
TI  - Retrorectus polyester mesh repair for midline ventral hernias.
AB  - PURPOSE: To evaluate the effectiveness of the retrorectus mesh repair for midline
      ventral hernias. METHODS: A retrospective review of all consecutive patients
      having a retrorectus mesh repair by a single surgeon in a standardized fashion
      from 1991 to 2005. All procedures used polyester (Mersilene) mesh with at least 5
      cm overlap beyond the repair in all directions. RESULTS: Ninety patients were
      identified, 56% of which were female. Major postoperative complications occurred
      in 23 (26%) patients, including nine (10%) patients requiring reoperative
      treatment due to skin flap necrosis, wound infection, hematoma, or fascial
      dehiscence. Partial mesh excision was required in four patients. The hernia
      recurrence rate was 7% at a mean of 53 months. CONCLUSION: The retrorectus repair
      with polyester mesh is an effective and durable repair for midline ventral
      hernias. The disadvantage of this repair is the large number of wound
      complications.

PMID- 19590818
TI  - Impact of operative time and surgeon satisfaction on the long-term outcome of
      hernia repair.
AB  - PURPOSE: The aim of this study was to assess the impact of the degree of
      difficulty and quality of hernia repair, as perceived by the surgeon, and
      operative time on the reoperation rate. METHODS: All hernia repairs performed
      during the period 1994-1995 at the Department of Surgery, University Hospital of
      Lund, Sweden, were recorded prospectively. The degree of difficulty and the
      degree of difficulty in relation to the preoperative expectation of the surgeon
      were graded on a three-degree scale, the final outcome graded as optimal or
      suboptimal, and the time required to perform the hernia repair was recorded.
      Recurrence repairs prior to 1998 were traced in a retrospective review of the
      patient notes. The Swedish Hernia Register was checked for reoperations from 1998
      and later. RESULTS: Altogether, 184 hernia repairs were recorded during the study
      period, including 14 repairs on women. The mean age of the patients was 58 years
      and the standard deviation was 15 years. Subsequent reoperation for recurrence
      was identified in 21 (11.4%) of these patients. The operative time correlated
      significantly with the surgeon's perception of the degree of difficulty (P <
      0.05). Operative time less than 20 min (n = 4) was significantly associated with
      increased risk for reoperation (P < 0.05). The degree of difficulty, the degree
      of difficulty in relation to preoperative expectation, and the assessment of the
      final outcome were not associated with the risk for reoperation. CONCLUSIONS:
      Although neither the grade of difficulty nor the surgeon's perception of the
      quality of repair significantly predicted the final outcome, the risk for
      reoperation increased if the repair was performed rapidly.

PMID- 19590819
TI  - Emergency laparoscopic treatment of acute incarcerated incisional hernia.
AB  - BACKGROUND: The emergency treatment of incisional hernias can be accomplished by
      a laparoscopic approach in order to avoid the common complications following open
      techniques. METHODS: From January 2001 to September 2007, we performed 48
      emergency laparoscopic treatments of incarcerated hernias. RESULTS: In our
      hospital, 320 patients with incisional hernia and 65 patients with primary
      abdominal wall hernia were treated laparoscopically. Forty-eight patients (30
      females and 18 males) underwent emergency surgery. The mean operative time was 62
      min (range 45-80 min). The average length of hospital stay was 4 days (range 3-6
      days). We had eight post-surgical seromas, all of which were treated successfully
      by needle aspiration. We saw no mesh sepsis and no metabolic or surgical
      complications. We had no recurrence nor the need for a second operation.
      Mortality was nil. CONCLUSIONS: The results of this series prove the feasibility
      of emergency laparoscopic surgery in incarcerated incisional hernias using new
      generation meshes.

PMID- 19590820
TI  - Fibrin sealant in inguinal hernioplasty: an observational multicentre study in
      1,201 patients.
AB  - PURPOSE: A prospective, multicentre, observational study was undertaken to assess
      Tisseel fibrin sealant for atraumatic mesh fixation in inguinal hernia repair
      throughout France. METHODS: Surgeons recorded data on patients undergoing tension
      free inguinal hernioplasty with mesh fixation with Tisseel, regardless of the
      hernioplasty technique used. Assessments were made at 2 days and 1 month after
      surgery. Data on local complications, operation times and ease of product use
      were collected. RESULTS: In total, 1,201 patients were recruited (90% men, mean
      age 57 years), among which 526 procedures were performed using open techniques
      and 675 using laparoscopic repairs. Local complications occurred in 4.7% of
      patients: 3.0% haematoma, 1.4% seroma, 0.3% recurrence. The mean visual analogue
      scale (VAS)-rated pain scores were 3.2 pre-operatively, 2.3 immediately after
      surgery and 1.8 at 1 month. Surgeons rated the product as very easy to use.
      CONCLUSIONS: Tisseel fibrin sealant appears to be a well-tolerated and easy-to
      use alternative to traditional, tissue-penetrating devices for mesh fixation in
      hernia repair techniques.

PMID- 19590821
TI  - Neuropsychiatric symptoms and the APOE genotype in Alzheimer's disease.
AB  - The study aimed to characterize neuropsychiatric symptomatology in Alzheimer's
      disease (AD) and investigate the role of APOE genotype and other clinical
      variables in the onset of neuropsychiatric disorders. Moreover, an attempt to
      study the evolution of behavioral and psychiatric symptoms was made. Fifty-three
      consecutive outpatients with AD were enrolled. Twenty-four were followed
      longitudinally for 1 year. MMSE was used to evaluate cognitive functions. The
      neuropsychiatric inventory (NPI) was administered to assess behavioral and
      psychiatric symptoms. Genotyping was determined through laboratory testing. At
      baseline, no specific neuropsychiatric disorder was significantly associated with
      ApoE genotype, but associated with a peculiar neuropsychiatric profile. Patients
      with epsilon(4) allele showed a wider range of neuropsychiatric disturbances when
      compared to non-carriers and higher scores for hallucinations and aberrant motor
      behaviors. The longitudinal results suggest different trends in both groups: over
      time, epsilon(4) carriers showed an increase/delayed onset in some symptoms and a
      parallel decrease in others, while non-carriers presented an undifferentiated
      worsening of symptomatology. Clear relations with other clinical and demographic
      variables were also found. APOE epsilon(4) allele is associated to a peculiar
      neuropsychiatric profile characterizing the onset and evolution of Alzheimer's
      disease.

PMID- 19590822
TI  - Selective involvement of temporal regions in a case of flavivirus encephalitis.
AB  - Clinical manifestations of flavivirus infection may be various, from unapparent
      to severe meningoencephalitis. Our patient, 2 weeks after returning home from a
      holiday at Elba Island, developed biphasic fever, later associated with nausea
      and vomiting and followed by incoming seizures responsive to thiopental sodium
      only. Brain MRI showed bilateral hyperintensity (T2) in amygdale, hippocampus,
      left insular and temporal inferior cortex. Standard and microbiological CSF
      examination was normal, but microbiological serum analysis showed seroconversion
      for flavivirus. The patient came to our observation 6 months after disease onset
      and at that time he was affected by frequent seizures and severe cognitive
      impairment with behavioural disturbances; the patient also showed distal weakness
      with footstepping. EEG showed bitemporal epileptic foci. During the following
      months, seizures greatly decreased and cognitive status improved in response to a
      complex antiepileptic therapy. Flavivirus encephalitis should be taken into
      account in the differential diagnosis of encephalitis selectively involving
      temporal lobes.

PMID- 19590824
TI  - Dietary supplementation of silymarin protects against chemically induced
      nephrotoxicity, inflammation and renal tumor promotion response.
AB  - Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxicant and a renal
      carcinogen that induces its effect by causing oxidative stress. The present study
      was undertaken to explore protective effect of silymarin, a flavonolignan from
      milk thistle (Silybum marianum), against Fe-NTA mediated renal oxidative stress,
      inflammation and tumor promotion response along with elucidation of the
      implicated mechanism(s). Administration of Fe-NTA (10 mg/kg bd wt, i.p.) to Swiss
      albino mice induced marked oxidative stress in kidney, evident from augmentation
      in renal metallothionein (MT) expression, depletion of glutathione content and
      activities of antioxidant and phase II metabolizing enzymes, and enhancement in
      production of aldehyde products such as 4-hydroxy-2-nonenal. Fe-NTA also
      significantly activated nuclear factor kappa B (NFkappaB) and upregulated the
      expression of downstream genes: cyclooxygenase 2 and inducible nitric oxide
      synthase and enhancing the production of proinflammatory cytokines: tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). However, feeding of
      0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA
      induced oxidative stress and inflammation. It further augmented MT expression,
      restored the antioxidant armory, ameliorated NFkappaB activation and decreased
      the expression of proinflammatory mediators. Silymarin also suppressed Fe-NTA
      induced hyperproliferation in kidney, ameliorating renal ornithine decarboxylase
      activity and DNA synthesis. From these results, it could be concluded that
      silymarin markedly protects against chemically induced renal cancer and acts
      plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative
      activities.

PMID- 19590825
TI  - Protease-resistant core form of Bacillus thuringiensis Cry1Ie: monomeric and
      oligomeric forms in solution.
AB  - Cry1Ie is encoded by cry1Ie, a gene that is silent in Bacillus thuringiensis
      strains but can be over-expressed in Escherichia coli. A protease-resistant core
      form of Cry1Ie with a molecular weight of approx. 55 kDa was found among the
      products of trypsin digestion. The oligomer and monomer of the protease-resistant
      core form were purified separately. The oligomer fraction contained a small
      quantity of dimer and a large amount of aggregates larger than tetramers. The 50%
      lethal concentrations (LC(50)) of the full-length Cry1Ie and both the monomer and
      oligomer fractions of the protease-resistant core form against Plutella
      xylostella were 14, 21 and 1400 microg/ml, respectively.

PMID- 19590826
TI  - Advances in enzyme immobilisation.
AB  - Improvements in current strategies for carrier-based immobilisation have been
      developed using hetero-functionalised supports that enhance the binding efficacy
      and stability through multipoint attachment. New commercial resins (Sepabeads)
      exhibit improved protein binding capacity. Novel methods of enzyme self
      immobilisation have been developed (CLEC, CLEA, Spherezyme), as well as carrier
      materials (Dendrispheres), encapsulation (PEI Microspheres), and entrapment.
      Apart from retention, recovery and stabilisation, other advantages to enzyme
      immobilisation have emerged, such as enhanced enzyme activity, modification of
      substrate selectivity and enantioselectivity, and multi-enzyme reactions. These
      advances promise to enhance the roles of immobilisation enzymes in industry,
      while opening the door for novel applications.

PMID- 19590823
TI  - Polyunsaturated fatty acids and cardiovascular disease.
AB  - Replacing saturated with polyunsaturated (PUFAs) rather than monounsaturated
      fatty acids or carbohydrates results in cardiovascular prevention over a wide
      range of intakes. The mechanisms by which PUFAs reduce cardiovascular risk are
      manifold, and the extent and precise nature of their activities is the subject of
      several investigations, spanning from in vitro mechanistic studies to human
      intervention trials. This article reviews the most up-to-date evidence of the
      association between PUFA consumption and reduced cardiovascular mortality.

PMID- 19590828
TI  - GroES and GroEL are essential chaperones for refolding of recombinant human
      phospholipid scramblase 1 in E. coli.
AB  - Human phospholipid scramblase 1(hPLSCR1), when expressed in E. coli (BL-21 DE3),
      forms inclusion bodies that are functionally inactive. We studied the effects of
      various stress inducing agents and chaperones on soluble expression of hPLSCR1 in
      E. coli (BL-21 DE3). Addition of 3% (v/v) ethanol before induction and decreasing
      the post-induction temperature to 15 degrees C increased the solubility of
      hPLSCR1 to approximately 10 and approximately 15% respectively. Presence of groES
      groEL complex solubilized the hPLSCR1 to approximately 30% of the total hPLSCR1.
      Absence of groES-groEL did not improve the solubility of hPLSCR1 suggesting that
      groES and groEL are the essential chaperones for the correct folding of hPLSCR1
      when over-expressed in E. coli.

PMID- 19590827
TI  - Novel desosaminyl derivatives of dihydrochalcomycin from a genetically engineered
      strain of Streptomyces sp.
AB  - Dihydrochalcomycin from Streptomyces sp. KCTC 0041BP is a 16-membered macrolide
      antibiotic containing two deoxysugars (D-chalcose and D-mycinose) that are O
      glycosylated at the C-5 and C-20 positions, respectively. The desosamine sugar
      cassette was constructed from pikromycin-deoxysugar biosynthetic genes and
      transformed into Streptomyces sp. GerSM1, which was engineered for deletion of
      the genes related to TDP-D-chalcose biosynthesis (gerB, gerN and gerMI). Novel 16
      membered macrolides (5-O-desosaminyl derivatives of dihydrochalcomycin) were
      detected by ESI-MS, LC/MS, and MS/MS thereby demonstrating combinatorial
      biosynthesis of the deoxysugar in 16-membered macrolide antibiotics.

PMID- 19590829
TI  - Inhibition of lung metastasis in mice by intravascular injection of dendritic
      cells and natural killer cells.
AB  - To investigate the efficacy of dendritic cells and natural killer cells in the
      inhibition of lung metastasis, we injected dendritic cells and natural killer
      cells intravascularly into mice bearing B16F10 tumour melanoma cells. This
      efficiently inhibited tumor growth and prolonged survival. In addition, surviving
      mice developed a long-lasting memory response against the original tumor when re
      challenged with live tumor cells. Intravenous administration of dendritic cells
      and natural killer cells may be a potential way to treat lung metastasis in
      patients.

PMID- 19590831
TI  - The ruthenium complex cis-(Dichloro)Tetraammineruthenium(III) chloride presents
      immune stimulatory activity on human peripheral blood mononuclear cells.
AB  - Ruthenium compounds in general are well suited for medicinal applications. They
      have been investigated as immunosuppressants, nitric oxide scavengers,
      antimicrobial agents, and antimalarials. The aim of this study is to evaluate the
      immunomodulatory activity of cis-(dichloro)tetraammineruthenium(III) chloride
      (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC).
      The cytotoxic studies performed here revealed that the ruthenium(III) complex
      presents a cytotoxic activity towards normal human PBMC, only at very high
      concentration. Results also showed that cis-[RuCl(2)(NH(3))(4)]Cl presents a dual
      role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low
      concentration and inducing cytotoxicity, inability to proliferate, and inhibiting
      IL-2 production at high concentration. The noncytotoxic activity of cis
      [RuCl(2)(NH(3))(4)]Cl at low concentration towards PBMC, which correlates with
      the small number of annexin V positive cells and also the absence of DNA
      fragmentation, suggest that this compound does not induce apoptosis on PBMC. For
      the first time, we show that, at low concentration (10-100 microg L(-1)), the cis
      [RuCl(2)(NH(3))(4)]Cl compound induces peripheral blood lymphocytes proliferation
      and also stimulates them to IL-2 production. These results open a new potential
      applicability of ruthenium(III) complexes as a possible immune regulatory
      compound acting as immune suppressor at high concentration and as immune
      stimulator at low concentration.

PMID- 19590830
TI  - Characterization of ATPase activity of class II chaperonin from the
      hyperthermophilic archaeon Pyrococcus furiosus.
AB  - To understand how molecular damage under harsh environmental conditions can be
      controlled, we investigated the properties of ATPase activity of the chaperonin
      molecular machinery from the hyperthermophilic archaeon Pyrococcus furiosus
      (PfCPN). PfCPN ATPase activity depended on K(+) and Mg(2+) and its optimal pH was
      7.5. PfCPN had almost no ADPase activity. ADP strongly competitively inhibited
      PfCPN ATPase activity. Inhibition of PfCPN ATPase decreased its chaperonin
      activity in protecting lysozyme from heat-induced inactivation.

PMID- 19590832
TI  - [Neuromuscular monitoring in patients with neuromuscular diseases. Options and
      needs].
AB  - The management of general anaesthesia in patients with neuromuscular disorders
      remains challenging. The underlying causes and clinical presentations of these
      rare heterogeneous diseases are highly variable and the only common feature is
      usually skeletal muscle weakness. The appropriate choice and dosage of muscle
      relaxants are important and an adequate monitoring of the neuromuscular blockade
      is obligatory. Neuromuscular monitoring can be complicated because of disease
      induced alterations in neurophysiology; however, continuous monitoring of the
      neuromuscular blockade should be realized to accurately determine the recovery
      from the blockade. These patients very often have an increased risk for
      postoperative pulmonary complications, which increases further if a residual
      neuromuscular blockade is present.

PMID- 19590833
TI  - [Adder bite. A rare dermatologic emergency].
AB  - Bites by poisonous snakes are rare dermatologic emergencies. A 43-year-old woman
      was bitten on her right forefinger by an adder during a hiking vacation in
      Austria. Her right arm and chest wall became swollen and then hemorrhagic, but
      she responded well to analgesics and immobilization. Administration of a specific
      antiserum was not necessary because of the lack of a systemic reaction.

PMID- 19590834
TI  - MLPA subtelomere analysis in Tunisian mentally retarded patients.
AB  - Subtelomeric rearrangements significantly contribute to idiopathic mental
      retardation and result in several mental retardation syndromes; however, most
      subtelomeric defects lack a characteristic phenotype. Thirty patients with
      unexplained mental retardation, a normal R banded karyotype at the 550 band, and
      no clinically recognizable syndrome were screened by Multiplex ligation-dependent
      probe amplification (MLPA). Four anomalies were identified: deletion 17q,
      duplications (4q), and associated duplications 15q and Xq. This duplication was
      found in two sisters of the proband. Anomalies were unidentified by the
      conventional technique. The prevalence of subtelomeric imbalances in our cohort
      of moderate to severe mental retardation is around 13% and is consistent with the
      literature. The sensitivity of the MLPA technique was characterized on
      cytogenetically verified positive and negative controls. MLPA is a fast,
      reliable, and relatively inexpensive technique to detect subtelomeric
      rearrangement in comparison with the fluorescence in situ hybridization (FISH)
      technique.

PMID- 19590836
TI  - Thinking inside and outside the envelopes of bone: dedicated to PDD.
AB  - INTRODUCTION: Bone modeling and remodeling is the final common pathway expressing
      all genetic and environmental factors that influence the attainment and
      maintenance of bone's material and structural strength. Modeling and remodeling
      require a surface, and during growth this cellular machinery fashions bone's
      external size, shape, and internal architecture by depositing bone on, and
      removing bone from, both its periosteal (external) and endosteal (internal)
      envelopes. Bone is distributed and redistributed to achieve strength commensurate
      with its loading requirements. METHODS: Advancing age is associated with: (1) a
      reduction in the volume of bone resorbed by each basic multicellular unit (BMU);
      (2) an even greater reduction in the volume of bone formed by each BMU so that
      each remodeling event, whether adaptive or reparative, removes bone from the
      bone; (3) increased remodeling (number of BMUs) on the three (endocortical,
      intracortical, and trabecular) components of its endosteal envelope in midlife in
      women and late in life in both sexes; and (4) reduced bone formation on the
      periosteal envelope. The net effect is cortical thinning, increased intracortical
      porosity, trabecular thinning, and loss of connectivity. RESULTS: While
      remodeling intensity on an envelope determines structure (e.g., trabecular
      perforations), the surface area of the envelope determines remodeling intensity,
      and, so, structure. High remodeling on trabecular surfaces decreases as
      trabeculae (with their surface) are lost. Conversely, remodeling on the
      endocortical and intracortical envelopes increases their surface area, so
      remodeling intensity increases and bone loss becomes predominantly cortical.
      CONCLUSIONS: Understanding bone structural strength and its decay and the effects
      of genetic factors, exercise, nutrition, and drug therapy on bone requires
      thinking outside and inside these envelopes; their absolute and relative
      movements during growth and aging determine bone structure and its strength.

PMID- 19590837
TI  - Bone turnover in age-related osteoporosis: early contributions of Pierre Delmas.

PMID- 19590838
TI  - Cortical and trabecular architecture are altered in postmenopausal women with
      fractures.

PMID- 19590839
TI  - [Finger-free speech with the Provox FreeHands HME Automatic Tracheostoma Valve
      system. Clinical long-term experience].
AB  - INTRODUCTION: The use of voice prostheses allows excellent rehabilitation of
      laryngectomized patients but it is considered a disadvantage that the
      tracheostoma must be closed manually for speech production. This limits their
      ability to simultaneously communicate by gestures or to work with both hands. An
      automatic tracheostoma valve helps patients to overcome this problem. PATIENTS,
      MATERIAL AND METHODS: A total of 17 laryngectomized patients were asked to join a
      long-term study 18 months after having been fitted with a Provox FreeHands HME
      Automatic Tracheostoma Valve system. The patients completed a questionnaire in
      order to assess satisfaction, voice quality, wearing comfort, fixation, potential
      problems and the effectiveness of the HME cassette. RESULTS: Of the 17 patients 4
      discontinued the study due to problems of securing the valve to the skin (n=2) or
      fistula leakage (n=2). Of the remaining patients 7 wore the valve daily for an
      average of 6 h. Of the patients 76% considered it a great advantage to be able to
      speak without using their hands. With the Provox FreeHands HME Automatic
      Tracheostoma Valve system, maximum phonation time was 8.5 s (+/-6.8) and the
      dynamic range was 21.7 decibels (+/-5.6). CONCLUSION: The results show that the
      Provox FreeHands HME Automatic Tracheostoma Valve system not only allows hands
      free speech but is also associated with excellent long-term compliance and good
      voice rehabilitation.

PMID- 19590840
TI  - [New developments in cochlear implantation].

PMID- 19590841
TI  - [Present state of cochlear implant treatment in adults and children].
AB  - The technique of cochlear implantation was the first method which allowed
      replacement of a sense organ by a (partially) implantable electronic prosthesis.
      By this method the cells of the spiral ganglion of the cochlea are directly
      stimulated by the electrodes introduced into the cochlea, bypassing the functions
      of the outer and middle ear as well as the cochlea. Treatment with a cochlear
      implant (CI) has been established over the last 20-30 years as a reliable method
      for restoring hearing in adults and children with severe hearing disorders and is
      now a routine method in many centers. For optimal results in understanding speech
      and for children in the speech development phase, rehabilitation must be an
      integral part of the total treatment and follow soon after implantation. To
      achieve this early diagnosis of hearing difficulties or deafness is necessary,
      which is simplified by a consistent hearing screening of newborns, now a
      statutory procedure in Germany.

PMID- 19590842
TI  - [Diagnostics in pulmonary hypertension].
AB  - Commonly, pulmonary hypertension is clinically suspected because of unexplained
      exertional dyspnoea or as a chance finding in clinical examination revealing
      signs of right heart failure. The systematic diagnostic approach and exact
      classification is based on the Venice classification. Basic investigations
      include ECG, chest radiograph, lung function studies and echocardiography.
      Echocardiography is the most important investigation for the diagnosis of
      pulmonary hypertension. It also serves as non invasive control during treatment
      and as the main screening test for pulmonary hypertension. Echocardiographic
      criteria of pulmonary hypertension are a dilated and hypertrophied right
      ventricle, paradoxic septum movement, a dilated right atrium, and a distended
      inferior Vena cava. Using Doppler echocardiography, the right ventricular and
      thus pulmonary arterial systolic pressure can be determined from the tricuspid
      regurgitant jet velocity. CT of the chest serves to exclude pulmonary embolism
      and interstitial lung disorders. Cardiac MRI is increasingly being used for
      analysis of right ventricular morphology, function and haemdynamics. The 6 minute
      walk test and cardiopulmonary exercise test are used to assess severity and
      response to treatment and give prognostic information. For the definite diagnosis
      of pulmonary hypertension, right heart catheterisation is required for the
      determination of the pulmonary vascular resistance and pharmacological testing of
      "reversibility".

PMID- 19590844
TI  - [Cerebellar syndrome in Gaucher's disease].
AB  - This is a report on a 37-year-old female patient with enzymatically verified
      Gaucher's disease. The clinical symptoms corresponded to the neuronopathic form
      of the disease (type 3). A progressive cerebellar syndrome had been developing
      for 1 year. So far, there have been no records of complex cerebellar symptoms in
      connection with Gaucher's disease in the literature. After ruling out other
      differential diagnoses Gaucher's disease was considered to be the cause of such
      cerebellar symptoms, which could be attributed to toxic glucocerebroside deposits
      in the cerebellum.

PMID- 19590843
TI  - p66(Shc) protein, oxidative stress, and cardiovascular complications of diabetes:
      the missing link.
AB  - Diabetes affects more than 150 million people worldwide, and it is estimated that
      this would increase to 299 million by the year 2025. The incidence of and
      mortality from cardiovascular disease are two- to eightfold higher in subjects
      with diabetes than in those without, coronary artery disease accounting for the
      large majority of deaths. Among the full spectrum of biochemical effects of high
      glucose, generation of oxygen-derived free radicals is one of the main
      pathophysiological mechanisms linking hyperglycemia to atherosclerosis,
      nephropathy, and cardiomyopathy. The adaptor protein p66(Shc) is implicated in
      mitochondrial reactive oxygen species (ROS) generation and translation of
      oxidative signals into apoptosis. Indeed, p66(Shc-/-) mice display prolonged
      lifespan, reduced production of intracellular oxidants, and increased resistance
      to oxidative stress-induced apoptosis. Accordingly, a series of studies defined
      the pathophysiological role of p66(Shc) in cardiovascular disease where ROS
      represent a substantial triggering component. As p66(Shc) modulates the
      production of cellular ROS, it represents a proximal node through which high
      glucose exerts its deleterious effects on different cell types; indeed, several
      studies tested the hypothesis that deletion of the p66(Shc) gene may confer
      protection against diabetes-related cardiovascular complications. The present
      review focuses on the reported evidence linking p66(Shc) signaling pathway to
      high glucose-associated endothelial dysfunction, atherogenesis, nephropathy, and
      cardiomyopathy.

PMID- 19590845
TI  - [Vertigo in children. Clinical presentation, course and treatment].
AB  - The diagnosis of vertigo syndromes in childhood is considered a difficult
      challenge. A correct diagnosis, however, makes successful therapy possible,
      prevents unnecessary investigations and alleviates the worries of parents.
      Migraine-associated forms of vertigo are very common in children (benign
      paroxysmal vertigo of childhood, vestibular migraine) and account for about 50%
      of diagnoses. Acute unilateral vestibular failure in the course of infectious and
      para-infectious labyrinthitis is also more common in children than in adults.
      Motion sickness is a frequent and relevant problem in children aged 4-10 years
      old. A number of rare congenital syndromes can occur with bilateral vestibular
      failure. Because of the relatively high frequency of brainstem and cerebellar
      tumors in children, MRI should be considered in all patients presenting with
      subacute central vestibular signs. In principle, all forms of vertigo known in
      adult patients can also occur in children; however, they must gradually be
      included in the diagnostic spectrum of the primary care physician (e.g.,
      vestibular paroxysm).

PMID- 19590846
TI  - Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose
      tolerance: does it matter for prevention and treatment of type 2 diabetes?
AB  - Prior to the development of type 2 diabetes, glucose levels increase into the
      prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated
      impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding
      of the aetiology and pathophysiology of the prediabetic states might give a basis
      for the development of individualised prevention and treatment strategies for
      type 2 diabetes. Several studies have examined mechanisms and potential
      aetiological factors leading to the development of the different prediabetic
      states. The pathophysiology of i-IFG seems to include the following key defects:
      reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or
      chronic low beta cell mass, altered glucagon-like peptide-1 secretion and
      inappropriately elevated glucagon secretion. Conversely, the prediabetic state i
      IGT is characterised by reduced peripheral insulin sensitivity, near-normal
      hepatic insulin sensitivity, progressive loss of beta cell function, reduced
      secretion of glucose-dependent insulinotropic polypeptide and inappropriately
      elevated glucagon secretion. Individuals developing combined IFG/IGT exhibit
      severe defects in both peripheral and hepatic insulin sensitivity as well as a
      progressive loss of beta cell function. The aetiologies of i-IFG and i-IGT also
      seem to differ, with i-IFG being predominantly related to genetic factors,
      smoking and male sex, while i-IGT is predominantly related to physical
      inactivity, unhealthy diet and short stature. Since the transition from the
      prediabetic states to overt type 2 diabetes is characterised by a non-reversible
      vicious cycle that includes severe deleterious effects on glucose metabolism,
      there are good reasons to use the well-established aetiological and
      pathophysiological differences in i-IFG, i-IGT and IFG/IGT to design
      individualised preventive strategies.

PMID- 19590847
TI  - Microarray analysis of genes with impaired insulin regulation in the skeletal
      muscle of type 2 diabetic patients indicates the involvement of basic helix-loop
      helix domain-containing, class B, 2 protein (BHLHB2).
AB  - AIMS/HYPOTHESIS: One of the major processes by which insulin exerts its multiple
      biological actions is through gene expression regulation. Thus, the
      identification of transcription factors affected by insulin in target tissues
      represents an important challenge. The aim of the present study was to gain a
      greater insight into this issue through the identification of transcription
      factor genes with insulin-regulated expression in human skeletal muscle. METHODS:
      Using microarray analysis, we defined the sets of genes modulated during a 3 h
      hyperinsulinaemic-euglycaemic clamp (2 mU min(-1) kg(-1)) in the skeletal muscle
      of insulin-sensitive control volunteers and in moderately obese insulin-resistant
      type 2 diabetic patients. RESULTS: Of the 1,529 and 1,499 genes regulated during
      the clamp in control and diabetic volunteers, respectively, we identified 30
      transcription factors with impaired insulin-regulation in type 2 diabetic
      patients. Analysis of the promoters of the genes encoding these factors revealed
      a possible contribution of the transcriptional repressor basic helix-loop-helix
      domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is
      strongly altered in the muscle of diabetic patients. Gene ontology analysis of
      BHLHB2 target genes, identified after BHLHB2 overexpression in human primary
      myotubes, demonstrated that about 10% of the genes regulated in vivo during
      hyperinsulinaemia are potentially under the control of this repressor. The data
      also suggested that BHLHB2 is situated at the crossroads of a complex
      transcriptional network that is able to modulate major metabolic and biological
      pathways in skeletal muscle, including the regulation of a cluster of genes
      involved in muscle development and contraction. CONCLUSIONS/INTERPRETATION: We
      have identified BHLHB2 as a potential novel mediator of insulin transcriptional
      action in human skeletal muscle.

PMID- 19590848
TI  - Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1
      diabetes risk.
AB  - AIMS/HYPOTHESIS: Our aim was to determine the relationships between
      autoantibodies to zinc transporter 8 (ZnT8), genotypes of the ZnT8-encoding gene
      SLC30A8 and type 1 diabetes risk. METHODS: ZnT8 autoantibodies (ZnT8A) were
      measured in sera of 1,633 children with a first-degree family history of type 1
      diabetes and who were prospectively followed from birth. Antibodies were measured
      by Protein A-based radiobinding assays and COOH-terminal (R325, W325 or Q325
      variants) or NH(2)-terminal constructs of human ZnT8. SLC30A8 genotyping at
      single-nucleotide polymorphism (SNP) rs13266634 was performed on 1,170 children.
      RESULTS: Antibodies against COOH-terminal ZnT8 constructs (ZnT8A-COOH) developed
      in 58 children as early as 9 months of age (median 3 years). They were detected
      in 55 of 128 (43%) children with autoantibodies to insulin, GAD and/or insulinoma
      associated protein 2 and 34 of 42 (81%) who progressed to diabetes. The
      additional presence of ZnT8A-COOH stratified diabetes risk in islet autoantibody
      positive children (p < 0.0001). SLC30A8 genotype strongly influenced ZnT8A type
      and diabetes risk in ZnT8A-COOH-positive children. Antibody binding against the
      ZnT8 R325 variant was strictly correlated with the number of the corresponding
      SLC30A8 R325-encoding alleles, whereas binding against the W325 variant was
      highest in children who had SLC30A8 W325-encoding alleles (p = 0.001). Moreover,
      ZnT8A-COOH-positive children who carried homozygous SLC30A8 SNP rs13266634
      genotypes progressed faster to diabetes than those who were heterozygous (59%
      [95% CI 42.3-75.7%] vs 22% [95% CI 0-44.3%] within 5 years; p = 0.01).
      CONCLUSIONS/INTERPRETATION: Autoimmunity against the COOH-terminal region of ZnT8
      is a highly relevant prognostic feature in childhood type 1 diabetes. Risk
      stratification in ZnT8A-COOH-positive children is further improved by SLC30A8
      genotyping.

PMID- 19590849
TI  - Cardiac death or circulatory arrest? Facts and values in organ retrieval after
      diagnosis of death by cardio-circulatory criteria.

PMID- 19590850
TI  - Effect of oxygen affinity on systemic perfusion and brain tissue oxygen tension
      after extreme hemodilution with hemoglobin-starch conjugates in rats.
AB  - PURPOSE: To determine the oxygen affinity for optimal tissue oxygen delivery with
      a hemoglobin-hydroxyethyl starch conjugate (HRC 101). METHODS: Anesthetized rats
      were hemodiluted (180 ml kg(-1)) with low (P(50) approximately 70 mmHg) or high
      affinity (P(50) approximately 14 mmHg) HRC 101 at hemoglobin (Hb) concentrations
      near 100 or 70 g l(-1) (n = 6-8). Hippocampal tissue oxygen tension (P(Br)O(2)),
      blood flow, arterial blood gases, Hb, hematocrit (Hct) and lactate were measured.
      Data (mean +/- SD) were analyzed by two-way ANOVA. RESULTS: Hemodilution reduced
      the hematocrit to 1 +/- 1% in all groups. P(Br)O(2) was best maintained after
      hemodilution with low affinity HRC 101 at Hb 100 and 70 g l(-1) (25.2 +/- 7.6 and
      16.6 +/- 8.3 torr, respectively). P(Br)O(2) decreased (9.5 +/- 9.3 torr, P <
      0.05) and serum lactate levels increased (5.0 +/- 1.7 mmol l(-1), P < 0.05)
      following hemodilution with the high affinity HRC 101 (Hb 100 g l(-1)).
      CONCLUSIONS: HRC 101 with a lower oxygen affinity favored tissue perfusion and
      maintained P(Br)O(2) after near complete blood volume exchange in rats.

PMID- 19590851
TI  - Juvenile Tillaux fracture with disrupted anteroinferior tibiofibular ligament: a
      case report.
AB  - The juvenile Tillaux fracture is an avulsion fracture of the anterolateral corner
      of the distal tibial epiphysis. This type of fracture occurs when the
      anteroinferior tibiofibular ligament, with the foot position of supination
      eversion or external rotation, avulses an epiphyseal fragment. Therefore, the
      anteroinferior tibiofibular ligament plays an important role in this injury, and
      usually remains intact. Here, we present a case in which the distal epiphyseal
      fragment was severely displaced and inverted, and the anteroinferior tibiofibular
      ligament was totally disrupted.

PMID- 19590853
TI  - Distribution of injury mechanisms and related factors in ACL-injured female
      carving skiers.
AB  - While ACL injury mechanisms in skiers using traditional skis are well studied, no
      study has yet investigated the distribution of injury mechanisms in carving
      skiers. In traditional skiers, the backward twisting fall seems to be the
      dominant injury mechanism, especially in female skiers. Female recreational
      skiers have a threefold higher risk to sustain an ACL injury than male skiers;
      therefore, it is important to determine if carving skis influence the
      distribution of injury mechanisms and the related frequencies of ACL injuries in
      female skiers. We investigated the frequencies of injury mechanisms and related
      factors in 65 ACL-injured female carving skiers by questionnaire. The forward
      twisting fall was the most reported ACL injury mechanism with about 51%, followed
      by the backward twisting fall within 29% of cases. Catching an edge of the ski
      (59 vs. 24%, P = 0.03) when executing turns (69 vs. 41%, P = 0.053) was a more
      frequent cause for forward twisting falls than for the other types of falling.
      While 29% of bindings released during a forward twisting fall, only 3.1% released
      during the remaining mechanisms. In contrast to traditional skiers, the forward
      twisting fall was the dominant injury mechanism in female carving skiers with ACL
      injury.

PMID- 19590852
TI  - The role of anterior cruciate ligament reconstruction in the older patients, 55
      years or above.
AB  - Anterior cruciate ligament (ACL) deficiency can result in symptomatic functional
      instability of the knee regardless of the patient's age. We reviewed a single
      surgeon database of 908 ACL reconstructions carried out in the last 20 years for
      symptomatic instability. 14 patients were identified who were 55 years or above
      at surgery (mean: 60 years, range 55-75 years). Patients were evaluated
      clinically and with clinical outcome scoring and KT-1000 arthrometry assessment.
      12 patients (86%) were available to attend for follow-up at a mean 9 years after
      ACL reconstruction. The median pre-injury Tegner score was 5.5 (range 1-7) and
      the median pre-operative Lysholm score was 33 (range 15-67). Initially, one
      patient had a good result but subsequently the patient undergone total knee
      replacement 5 years after ACL reconstruction. For the remainder, at the most
      recent review, the median Lysholm score had improved to 79 (range 43-100, P <
      0.05) although it had deteriorated from the maximum achieved post-op score of
      85.5 (range 53-100, P < 0.05); and the Tegner score had declined to 3 (range 1-5,
      P < 0.05). KT-1000 testing demonstrated a mean side-to-side difference
      improvement in laxity from 4.6 +/- 1.3 mm (range 3-7) to 1.5 +/- 1.2 mm (range 0
      4, P < 0.05) and >2 mm difference in only one knee (for which it was known that
      the graft had failed at 11 years after ACL reconstruction). At review, the same
      knee was the only one that demonstrated a pivot shift. ACL reconstruction with
      autograft in the above-55 patient with minimal osteoarthritis is a safe procedure
      that returns stability to the knee and permits a return to a reasonable level of
      activity.

PMID- 19590855
TI  - Under-meniscal portal: an alternative portal for an easy access to the medial and
      lateral menisci.
AB  - Approach to the pathologies in the posterior horn of the medial meniscus in a
      tight knee may be a challenging technique to the arthroscopic surgeon in certain
      patients. The pie-crusting technique of the medial collateral ligament which can
      be done percutaneously to open up a tight posteromedial compartment would be a
      good option in such patients. Here, the authors introduce a useful alternative
      portal for approaching the posterior horn of the medial meniscus, the under
      meniscal portal. The under-meniscal portal is located under the menisci and can
      be placed safely and easily without any complication. It is also helpful for
      approaching the unstable underside of the horizontal tear in the anterior horn of
      the lateral meniscus. The authors suggest the under-meniscal portal as a good
      alternative portal for managing challenging lesions in the posterior horn of the
      medial meniscus and the anterior horn of the lateral meniscus.

PMID- 19590854
TI  - Recurrence of synovial chondromatosis of the Hoffa's body.
AB  - Synovial chondromatosis of Hoffa's body is uncommon. Recurrences usually result
      from incomplete removal of the loose bodies or diseased synovium at the initial
      surgery. We report a patient with synovial chondromatosis localized into the
      Hoffa's body who presented with anterior knee pain and mechanical symptoms. At
      the first arthroscopy, all pathological tissue was removed. At 1-year follow-up,
      clinical and radiographic examinations were normal. Symptoms recurred at 3 years,
      when a bony mass in the Hoffa's body was evident on MRI. The mass was removed
      through a mini-arthrotomy. Histology excluded malignancy. At 10-year follow-up,
      the patient remained free of symptoms. Synovial chondromatosis can occur with
      unusual patterns of recurrence. The growth of a large size mass confined to fat
      pad without intra-articular involvement does not allow to exclude the diagnosis
      of recurrent synovial chondromatosis.

PMID- 19590856
TI  - Analysis of autophosphorylation sites in the recombinant catalytic subunit alpha
      of cAMP-dependent kinase by nano-UPLC-ESI-MS/MS.
AB  - The catalytic subunit of recombinant wild-type cyclic adenosine monophosphate
      dependent protein kinase A (PKA) has been analyzed by a combination of 1D gel
      electrophoresis, in-gel digestion by trypsin, chymotrypsin, or endoproteinase
      AspN, and nano-ultraperformance liquid chromatography--MS/MS. The MS/MS spectra
      were annotated by MASCOT and the annotations were manually controlled. Using
      Ga(III)-immobilized metal ion affinity chromatography (IMAC), in addition to the
      four established autophosphorylation sites of the catalytic subunit of
      recombinant PKA, pSer10, pSer139, pThr197, and pSer338, six new phosphorylated
      residues have been characterized--pSer14, pThr48, pSer53, pSer212, pSer259, and
      pSer325. The established phosphorylation sites all are part of a PKA consensus
      motif and were found to be almost completely modified. In contrast, the newly
      detected sites were only partially phosphorylated. For estimation of their degree
      of phosphorylation, a method based on signal intensity measurements was used. For
      this purpose, signal intensities of all phospho- and non-phosphopeptides
      containing a particular site were added for estimation of site-specific
      phosphorylation degrees. This addition was performed over all peptides observed
      in the different digestion experiments, including their different charge states.
      pThr48 and pSer259 are located within PKA consensus motifs and were observed to
      be phosphorylated at 20% and 24%, respectively. pSer14 and pSer53 are located
      within inverted PKA consensus motifs and were found to be phosphorylated around
      10% and 15%, respectively. The sequence environments of pSer212 and pSer325 have
      no similarity to the PKA consensus motif at all and were observed to be
      phosphorylated at about 5% or lower. All newly observed phosphorylation sites are
      located at the surface of the native protein structure of the PKA catalytic
      subunit. The results add new information on the theme of site-specific
      (auto)phosphorylation by PKA.

PMID- 19590857
TI  - Analytical approach for characterization of cadmium-induced thiol peptides--a
      case study using Chlamydomonas reinhardtii.
AB  - Phytochelatins (PC) were described earlier to play a role in metal detoxification
      in Chlamydomonas reinhardtii but were not clearly identified. The focus of this
      case study was to identify PC synthesized by C. reinhardtii exposed to Cd. Only
      low intracellular concentrations of cadmium (85 nmol g(-1) fresh weight) were
      sufficient to cause significant changes in thiol peptide pools. Thus, results
      showed a progressive decline of the glutathione content, accompanied by an
      induction of phytochelatins. Not only canonic phytochelatins but for the first
      time also the iso-phytochelatins CysPC(n) and PC(2)Ala were identified in this
      unicellular green alga using electrospray ionization quadrupole time-of-flight
      tandem mass spectrometry. Additionally, CysPC(n)desGly, PC(n)desGly, CysPC(n)Glu,
      and PC(2)Glu were found throughout MS analysis. Also, low abundant PCs could be
      detected due to the high sample preconcentration combined with little sample
      amounts (0.3 microL min(-1)) necessary for electrospray. Identified PCs had a
      maximum number of 5 gamma-glutamyl cysteine (gamma-GluCys) units. Thiol peptides
      of higher molecular masses suggesting PC(n) with n > 5 could be identified as
      intermolecular oxidation products of smaller PCs. Thiols may easily be oxidized.
      Therefore, PCs were reduced prior to MS analysis. Dithiothreitol and tris(2
      carboxyethyl) phosphine were compared concerning their reduction effort.

PMID- 19590858
TI  - Surface plasmon resonance immunosensor for cortisol and cortisone determination.
AB  - In this paper, we present a surface-plasmon-resonance-based immunosensor for the
      real-time detection of cortisol and cortisone levels in urine and saliva samples.
      The method proposed here is simple, rapid, economic, sensitive, robust, and
      reproducible thanks also to the special features of the polycarboxylate-hydrogel
      based coatings used for the antibody immobilization. The sensor surface displays
      a high level of stability during repeated regeneration and affinity reaction
      cycles. The immunosensor shows high specificity for cortisol and cortisone;
      furthermore, no significant interferences from other steroids with a similar
      chemical structure have been observed. The suitability of the hydrogel coating
      for the prevention of nonspecific binding is also investigated. A good
      correlation is noticed between the results obtained by the proposed method and
      the reference liquid chromatography/tandem mass spectrometry method for the
      analysis of cortisol and cortisone in urine and saliva samples. Standard curves
      for the detection of cortisol and cortisone in saliva and urine are characterized
      by a detection limit less than 10 microg l(-1), sufficiently sensitive for both
      clinical and forensic use.

PMID- 19590859
TI  - Combining eye and hand in search is suboptimal.
AB  - When performing everyday tasks, we often move our eyes and hand together: we look
      where we are reaching in order to better guide the hand. This coordinated pattern
      with the eye leading the hand is presumably optimal behaviour. But eyes and hands
      can move to different locations if they are involved in different tasks. To find
      out whether this leads to optimal performance, we studied the combination of
      visual and haptic search. We asked ten participants to perform a combined visual
      and haptic search for a target that was present in both modalities and compared
      their search times to those on visual only and haptic only search tasks. Without
      distractors, search times were faster for visual search than for haptic search.
      With many visual distractors, search times were longer for visual than for haptic
      search. For the combined search, performance was poorer than the optimal strategy
      whereby each modality searched a different part of the display. The results are
      consistent with several alternative accounts, for instance with vision and touch
      searching independently at the same time.

PMID- 19590860
TI  - Hypometria and bradykinesia during drawing movements in individuals with
      Parkinson's disease.
AB  - To address the hypothesis that Parkinson's disease (PD) patients have deficits in
      controlling acceleration, a drawing task was used in which target size,
      frequency, and weight of pen were manipulated. In accordance with previous
      results, it was found that, relative to controls, PD patients produced movements
      at the required frequency, but moved significantly slower, produced less
      acceleration, and drew smaller-than-required stroke sizes. This resulted in
      smaller-than-required movement amplitudes, suggesting that hypometria and
      bradykinesia in drawing and/or handwriting are related. Patients were found to
      perform similarly to controls when the target size was 1 cm. However, their
      performance became more dissimilar at greater stroke lengths. In addition to the
      aforementioned effects it was found that movement amplitude error was less when
      the pen was 20 times heavier than the normal pen and that the increased load may
      dampen abnormal limb-stiffness characteristics induced by PD.

PMID- 19590861
TI  - Dynamic responsiveness of lumbar paraspinal muscle spindles during vertebral
      movement in the cat.
AB  - Muscle spindles provide essential information for appropriate motor control. In
      appendicular muscles, much is known about their position and movement
      sensitivities, but little is known about the axial muscles of the low back. We
      investigated the dynamic responsiveness of lumbar paraspinal muscle spindle
      afferents from L(6) dorsal root filaments during constant velocity movement of
      the L(6) vertebra (the feline has seven lumbar vertebrae) in Nembutal
      anesthetized cats. Actuations of 1 mm applied at the L(6) spinous process were
      delivered at 0.5, 1.0 and 2.0 mm/s. The slow velocity component was measured as
      the slope of the relationship between displacement during the constant velocity
      ramp and instantaneous discharge frequency. The quick velocity component was the
      slope's intercept at zero displacement. The peak component was determined as the
      highest discharge rates occurring near the end of the ramp compared with control.
      The slow velocity component over the three increasing velocities was 23.9 (9.9),
      21.6 (9.6) and 20.5 (9.5) imp/(s mm) [mean (SD)], respectively. The quick
      velocity component was 28.4 (8.6), 31.4 (9.8) and 35.8 (10.6) imp/s,
      respectively. These measures of dynamic responsiveness were at least 5-10 times
      higher compared with values reported for appendicular muscle spindles. The peak
      component's velocity sensitivity was 2.9 (imp/s)/(mm/s) [0.2, 5.5, lower, upper
      95% confidence interval] similar to that for cervical paraspinal muscles as well
      as appendicular muscles. Increased dynamic responsiveness of lumbar paraspinal
      muscle spindles may insure central driving to insure control of intervertebral
      motion during changes in spinal orientation. It may also contribute to large,
      rapid and potentially injurious increases in paraspinal muscle activity during
      sudden and unexpected muscle stretch.

PMID- 19590863
TI  - The National Poison Center in Norway: user satisfaction and a health economic
      evaluation.
AB  - OBJECTIVES: The aim of the study was to find out how satisfied users are with the
      National Poison Center of Norway and to make a health economic evaluation of the
      service. METHOD: The material consisted of telephone interviews with 310 users of
      the service from the general public and 665 completed questionnaires from doctors
      and nurses. RESULTS: Most respondents were satisfied with the information and had
      followed the advice. They also felt safer after making a phone call. It was found
      that the running costs of the Poison Center are approximately the same as the
      estimated additional costs the health care system would incur if the service did
      not exist. CONCLUSIONS: Both users and health care personnel are highly satisfied
      with the Poison Center hotline. Even though the Norwegian health system does not
      necessarily save money by providing the service, the safety it provides cannot be
      measured in economic terms.

PMID- 19590862
TI  - Stimulus duration influences perceived simultaneity in audiovisual temporal-order
      judgment.
AB  - The temporal integration of stimuli in different sensory modalities plays a
      crucial role in multisensory processing. Previous studies using temporal-order
      judgments to determine the point of subjective simultaneity (PSS) with
      multisensory stimulation yielded conflicting results on modality-specific delays.
      While it is known that the relative stimulus intensities of stimuli from
      different sensory modalities affect their perceived temporal order, we have
      hypothesized that some of these discrepancies might be explained by a previously
      overlooked confounding factor, namely the duration of the stimulus. We therefore
      studied the influence of both factors on the PSS in a spatial-audiovisual
      temporal-order task. In addition to confirming previous results on the role of
      stimulus intensity, we report that varying the temporal duration of an
      audiovisual stimulus pair also affects the perceived temporal order of the
      auditory and visual stimulus components. Although individual PSS values varied
      from negative to positive values across participants, we found a systematic shift
      of PSS values in all participants toward a common attractor value with increasing
      stimulus duration. This resulted in a stabilization of PSS values with increasing
      stimulus duration, indicative of a mechanism that compensates individual
      imbalances between sensory modalities, which might arise from attentional biases
      toward one modality at short stimulus durations.

PMID- 19590865
TI  - Children's presence in research. A review of online registers.
AB  - OBJECTIVES: To determine how many online clinical trial registers include
      paediatric trial data, how much information is provided, ease of searching for
      paediatric trials and the accessibility of paediatric trial data in general.
      METHODS: Medline and Google were searched for mention of clinical trial registers
      in July 2008. All registers considered to be eligible were evaluated for trial
      information provided, search options available, and number of trials, both total
      and paediatric. A meta-analytic weighted average of the presence of paediatric
      trials was calculated and compared to the percentage of published paediatric
      trial articles in Medline. The paediatric trials in the registers were searched
      for in the World Health Organization's International Clinical Trials Registry
      Platform (ICTRP). All online, freely accessible registers including ongoing
      trials on different drugs or therapeutic areas, were eligible for review.
      RESULTS: Twelve registers were included in the review. All except one provided
      detailed trial data, while search options varied between registers: seven
      provided free-text searching, two listed their trials by condition, two provided
      elaborate search options (age group, condition, study purpose, etc) and one
      simply listed its trials. Nine of the 12 registers' search facilities made it
      possible to search for paediatric trials, and these were analysed further: the
      percentage of paediatric trials in the single registers ranged from 4.8 to 33.3%,
      and the weighted average was 15% (95% confidence interval 8.2-21.8). The
      percentage of published, paediatric trial articles was 25%. Of the paediatric
      trials also searched for in the ICTRP, 66% were found. CONCLUSIONS: Great
      difficulty was found in retrieving paediatric trials due to the limited and
      inadequate search functions of the registers reviewed but, in general, the
      registers seem to represent fewer paediatric trials than those reported in the
      literature. The ICTRP portal is important for trial accessibility, but it is
      still in an initial phase and far from representative of the global research
      situation, especially in the field of paediatrics.

PMID- 19590866
TI  - Gene cloning and expression of a new acidic family 7 endo-beta-1,3-1,4-glucanase
      from the acidophilic fungus Bispora sp. MEY-1.
AB  - Most reported microbial beta-1,3-1,4-glucanases belong to the glycoside hydrolase
      family 16. Here, we report a new acidic family 7 endo-beta-1,3-1,4-glucanase
      (Bgl7A) from the acidophilic fungus Bispora sp. MEY-1. The cDNA of Bgl7A was
      isolated and over-expressed in Pichia pastoris, with a yield of about 1,000 U ml(
      1) in a 3.7-l fermentor. The purified recombinant Bgl7A had three activity peaks
      at pH 1.5, 3.5, and 5.0 (maximum), respectively, and a temperature optimum at 60
      degrees C. The enzyme was stable at pH 1.0-8.0 and highly resistant to both
      pepsin and trypsin. Belonging to the group of non-specific endoglucanase, Bgl7A
      can hydrolyze not only beta-glucan and cellulose but also laminarin and oat spelt
      xylan. The specific activity of Bgl7A against barley beta-glucan and lichenan
      (4,040 and 2,740 U mg(-1)) was higher than toward carboxymethyl cellulose sodium
      (395 U mg(-1)), which was different from other family 7 endo-beta-glucanases.

PMID- 19590867
TI  - Biochemistry of microbial polyvinyl alcohol degradation.
AB  - Effect of minor chemical structures such as 1,2-diol content, ethylene content,
      tacticity, a degree of polymerization, and a degree of saponification of the main
      chain on biodegradability of polyvinyl alcohol (PVA) is summarized. Most PVA
      degraders are Gram-negative bacteria belonging to the Pseudomonads and
      Sphingomonads, but Gram-positive bacteria also have PVA-degrading abilities.
      Several examples show symbiotic degradation of PVA by different mechanisms.
      Penicillium sp. is the only reported eukaryotic degrader. A vinyl alcohol
      oligomer-utilizing fungus, Geotrichum fermentans WF9101, has also been reported.
      Lignolytic fungi have displayed non-specific degradation of PVA. Extensive
      published studies have established a two-step process for the biodegradation of
      PVA. Some bacteria excrete extracellular PVA oxidase to yield oxidized PVA, which
      is partly under spontaneous depolymerization and is further metabolized by the
      second step enzyme (hydrolase). On the other hand, PVA (whole and depolymerized
      to some extent) must be taken up into the periplasmic space of some Gram-negative
      bacteria, where PVA is oxidized by PVA dehydrogenase, coupled to a respiratory
      chain. The complete pva operon was identified in Sphingopyxis sp. 113P3.
      Anaerobic biodegradability of PVA has also been suggested.

PMID- 19590868
TI  - Biotechnological production of enantiopure epoxides by enzymatic kinetic
      resolution.
AB  - Enantiopure epoxides are high value-added synthons for the production of
      pharmaceuticals, agrochemicals, as well as versatile fine chemicals and have
      broad scope of market demand for their applications. A major challenge in
      conventional organic synthesis is to generate such compounds in high
      enantiopurity with reasonable yield. Among possible chemical and biological
      technologies for enantiopure epoxide preparation, enzymatic kinetic resolution
      has been paid much attention with respect to its high enantioselectivity. Epoxide
      hydrolase (EH) has shown promising characteristics for the preparation of
      enantiopure epoxides and vicinal diols during enantioselective hydrolysis of
      racemic epoxides. EH is readily available from microbial resources thus it is
      being employed for biohydrolysis of a variety of epoxides. Recent technical
      progress in EH-catalyzed enantioselective hydrolysis is summarized in terms of
      exploration of novel EH, its functional improvement, high throughput assay, and
      preparative scale resolution process.

PMID- 19590869
TI  - A method for obtaining DNA from compost.
AB  - An effective cell lysis method for extraction of bacterial genomic DNA from
      compost was developed in this study. Enzymatic disruption method, physical
      chemical combination method, and commercial kit method were used to extract DNA
      from compost samples and were compared by analyzing DNA yield and efficient cell
      lysis. The results showed that all the three methods can be used to extract high
      quality DNA from compost, but the enzymatic method had better cell lysis
      efficiency and DNA yields than others without the use of special equipment and
      expensive spending. Comparison of different methods for lysing gram-positive
      bacteria Bacillus subtilis indicated that the enzymatic cell lysis is superior
      for destroying the gram-positive cell wall. Spin-bind DNA column was used for DNA
      purification, and the purity of the purified sample was checked by polymerase
      chain reaction to amplify a region of the 16S rRNA. Results indicated that the
      part of 16S rRNA were amplified from all the purified DNA samples, and all the
      amplification products could be digested by the restriction enzyme HhaI.

PMID- 19590870
TI  - Structural and physicochemical properties of polar lipids from thermophilic
      archaea.
AB  - The essential general features required for lipid membranes of extremophilic
      archaea to fulfill biological functions are that they are in the liquid
      crystalline phase and have extremely low permeability of solutes that is much
      less temperature sensitive due to a lack of lipid-phase transition and highly
      branched isoprenoid chains. Many accumulated data indicate that the organism's
      response to extremely low pH is the opposite of that to high temperature. The
      high temperature adaptation does not require the tetraether lipids, while the
      adaptation of thermophiles to acidic environment requires the tetraether polar
      lipids. The presence of cyclopentane rings and the role of polar heads are not so
      straightforward regarding the correlations between fluidity and permeability of
      the lipid membrane. Due to the unique lipid structures and properties of archaeal
      lipids, they are a valuable resource in the development of novel biotechnological
      processes. This microreview focuses primarily on structural and physicochemical
      properties of polar lipids of (hyper)thermophilic archaea.

PMID- 19590871
TI  - Percutaneous ablation for bone and soft tissue metastases--why cryoablation?

PMID- 19590873
TI  - Therapy of hepatitis C in thalassemia: the influence of iron on achieving
      sustained viral response.

PMID- 19590872
TI  - Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor
      immunity through effects that extend beyond regulatory T cell elimination.
AB  - Using a model of established malignancy, we found that cyclophosphamide (Cy),
      administered at a dose not requiring hematopoietic stem cell support, is superior
      to low-dose total body irradiation in augmenting antitumor immunity. We observed
      that Cy administration resulted in expansion of tumor antigen-specific T cells
      and transient depletion of CD4(+)Foxp3(+) regulatory T cells (Tregs). The
      antitumor efficacy of Cy was not improved by administration of anti-CD25
      monoclonal antibody given to induce more profound Treg depletion. We found that
      Cy, through its myelosuppressive action, induced rebound myelopoiesis and
      perturbed dendritic cell (DC) homeostasis. The resulting DC turnover led to the
      emergence of tumor-infiltrating DCs that secreted more IL-12 and less IL-10
      compared to those from untreated tumor-bearing animals. These newly recruited
      DCs, originating from proliferating early DC progenitors, were fully capable of
      priming T cell responses and ineffective in inducing expansion of Tregs.
      Together, our results show that Cy-mediated antitumor effects extend beyond the
      well-documented cytotoxicity and lymphodepletion and include resetting the DC
      homeostasis, thus providing an excellent platform for integration with other
      immunotherapeutic strategies.

PMID- 19590875
TI  - Dermatomyositis and cutaneous metastases from breast cancer: simultaneous
      development and parallel course.
AB  - The association between dermatomyositis (DM) and various types of malignancies
      has been reported in several studies, with an estimated frequency of about 20
      25%. Cancer may appear before the onset of DM, concurrently with DM or after its
      onset. In the present report, the occurrence of typical DM in concomitance with
      development of skin metastases from previously treated breast cancer is
      described, suggesting the role of DM as paraneoplastic marker not only in
      association with the primary tumor but also in case of cutaneous involvement by
      cancer.

PMID- 19590874
TI  - Adherence to treatment guidelines in two primary care populations with gout.
AB  - Published guidelines for the treatment of gout aim to improve the evidenced-based
      management of this disorder. Unfortunately, several studies suggest that these
      guidelines are not routinely followed in clinical practice. Limited data exist
      comparing different groups of primary care providers regarding compliance with
      published gout guidelines. We conducted a retrospective study comparing two
      different general internal medicine (IM) practices and evaluated compliance with
      these guidelines. All patients with a billing code for gout seen in two large IM
      clinics (Clinic A, an inner-city urban clinic, and Clinic B, a suburban clinic)
      between January 2004 and December 2007 were selected for chart review. Patients
      referred to a rheumatologist for management of gout were excluded. The care
      received by these patients for gout was compared to recommendations from
      published guidelines, with the primary outcome assessing the percentage of
      patients who received at least yearly monitoring of serum uric acid (SUA) levels.
      In both clinics, yearly monitoring of SUA levels occurred in approximately one
      quarter of the patients with gout (Clinic A 27.5% vs. Clinic B 28.9%, P = 0.87).
      Compared to SUA, renal function was monitored more frequently in each of the
      groups. Listed indications for antihyperuricemic therapy were similar between
      groups, although gouty flares were reported more frequently in clinic B (P =
      0.005). In this retrospective review of gout management in two IM clinics,
      general care for patients with this condition did not differ significantly.
      However, overall compliance with recommendations from published guidelines was
      low.

PMID- 19590876
TI  - Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome.
AB  - Familial Mediterranean fever (FMF) is a genetic multisystem disorder of unknown
      etiology characterized by recurrent episodes of fever and pain due to acute
      inflammation of the peritoneum, synovia, or pleura. Up to 25% of patients with
      FMF report muscle pain. Myalgia may be a spontaneous pattern, exercise-induced
      pattern, or protracted febrile myalgia syndrome (PFMS). PFMS is characterized by
      severe paralyzing myalgia, high fever, abdominal pain, diarrhea,
      arthritis/arthralgia, and transient vasculitic rashes mimicking Henoch-Schonlein
      purpura. The episodes last for 4-6 weeks, except in those patients treated with
      corticosteroids. The PFMS may recur even under colchicine prophylaxis. We
      describe a 30-year-old pregnant Turkish woman with known FMF and under colchicine
      prophylaxis, with severe myalgia for 8 weeks, emphasizing the importance of a
      different clinical pattern of PFMS even in the absence of other symptoms.

PMID- 19590877
TI  - Reduced and reversed temperature dependence of blood oxygenation in an
      ectothermic scombrid fish: implications for the evolution of regional
      heterothermy?
AB  - Tunas (family Scombridae) are exceptional among most teleost fishes in that they
      possess vascular heat exchangers which allow heat retention in specific regions
      of the body (termed 'regional heterothermy'). Seemingly exclusive to
      heterothermic fishes is a markedly reduced temperature dependence of blood-oxygen
      (blood-O(2)) binding, or even a reversed temperature dependence where increasing
      temperature increases blood-O(2) affinity. These unusual binding properties have
      been documented in whole blood and in haemoglobin (Hb) solutions, and they are
      hypothesised to prevent oxygen loss from arteries to veins within the vascular
      heat exchangers and/or to prevent excessive oxygen unloading to the warm tissues
      and ensure an adequate supply of oxygen to tissues positioned efferent to the
      heat exchangers. The temperature sensitivity of blood-O(2) binding has not been
      characterised in an ectothermic scombrid (mackerels and bonitos), but the
      existence of the unusual binding properties in these fishes would have clear
      implications for their proposed association with regional heterothermy.
      Accordingly, the present study examined oxygenation of whole blood of the chub
      mackerel (Scomber japonicus) at 10, 20 and 30 degrees C and at 0.5, 1 and 2%
      CO(2). Oxygen affinity was generally highest at 20 degrees C for all levels of
      CO(2). Temperature-independent binding was observed at low (0.5%) CO(2), where
      the PO(2) at 50% blood-O(2) saturation (P (50)) was not statistically different
      at 10 and 30 degrees C (2.58 vs. 2.78 kPa, respectively) with an apparent heat of
      oxygenation (H degrees ) close to zero (-6 kJ mol(-1)). The most significant
      temperature-mediated difference occurred at high (2%) CO(2), where the P (50) at
      10 degrees C was twofold higher than that at 20 degrees C with a corresponding H
      degrees of +43 kJ mol(-1). These results provide clear evidence of independent
      and reversed open-system temperature effects on blood oxygenation in S.
      japonicus, and it is therefore speculated that these unusual blood-O(2) binding
      characteristics may have preceded the evolution of vascular heat exchangers and
      regional heterothermy in fishes.

PMID- 19590878
TI  - Cervical spinal cord infarction after posterior fossa surgery: a case-based
      update.
AB  - BACKGROUND: Several positions are currently utilized for operating patients with
      posterior fossa lesions. Each individual position has its own risks and benefits,
      and none has demonstrated its superiority. A dreaded, and probably underreported,
      complication of these procedures is cervical cord infarction with quadriplegia.
      DISCUSSION: We reviewed eight previous reported instances of this devastating
      complication aimed at ascertaining its pathogenesis to suggest preventive
      strategies. Several hypotheses have been put forward to explain the occurrence of
      this complication. Some factors involved in the production of cervical cord
      infarction include patient's position (seated or prone), hyperflexion of the
      neck, excessive spinal cord traction, canal stenosis, and systemic arterial
      hypotension. We hypothesize that spinal cord infarction in our patient might have
      resulted from compromised blood supply to the midcervical cord caused by tumor
      infiltration of the cervical leptomeninges in addition to a brief episode of
      arterial hypotension during venous air embolism. CASE REPORT: We treated an 8
      year-old girl who developed quadriplegia after surgery for a fourth ventricular
      ependymoma. Postoperative magnetic resonance imaging demonstrated cervical cord
      infarction. Evoked potentials confirmed the diagnosis. CONCLUSIONS: With this
      report, we want to draw the attention of neurosurgeons to the possibility of the
      occurrence of this dreadful complication during posterior fossa procedures.
      Retrospectively, the only measures that might have helped to avoid this
      complication in our patient would have been using the prone position and
      intraoperative monitoring of evoked potentials.

PMID- 19590879
TI  - Haemorrhoids are related to changes of cell function in mucosa and submucosa.
AB  - PURPOSE: Epidemiology and risk factors of haemorrhoidal disease are not well
      defined. This study tried to evaluate if the appearance of haemorrhoids is
      related to a disturbed remodelling of the soft tissue of rectal mucosa and
      submucosa. Therefore, immunohistochemical expression profiles of five parameters
      as potential mediators in neoangiogenesis (EGFR), in inflammatory cell activity
      (COX-2), and in cell migration, differentiation, and wound healing (notch-3, c
      myc, and beta-Catenin) were analysed (Saed et al., Fertil Steril 83(Suppl 1):1216
      1219, 1; Saed et al., Fertil Steril 79:1404-1408, 2; Stojadinovic et al., Am J
      Pathol 167:59-69, 3). METHODS: Haemorrhoidal tissue specimens were collected from
      44 patients. Healthy rectal mucosa was obtained from 16 non-fixed fresh cadavers
      and served as control. Histological and immunohistochemical markers like EGFR,
      COX-2, notch-3, c-myc, and beta-Catenin were analysed semi-quantitatively,
      separately for mucosal and submucosal layer. RESULTS: Significantly increased
      expressions were found for EGFR, COX-2, and notch-3 in the mucosal and submucosal
      layer of haemorrhoidal tissue in comparison to normal rectal tissue. CONCLUSIONS:
      This finding confirms that haemorrhoidal disease may be regarded as a
      manifestation of a soft tissue disease.

PMID- 19590880
TI  - Inflammatory myopathy with abundant macrophages and dermatomyositis: two stages
      of one disorder or two distinct entities?
AB  - Inflammatory myopathy with abundant macrophages (IMAM) and dermatomyositis (DM)
      are considered to represent related disorders, since they share inflammatory
      infiltrates and skin alterations. In order to get more insight into these
      disorders, we addressed the cellular composition of the inflammatory infiltrates
      in muscle biopsies of 11 patients with IMAM and DM. In IMAM, inflammatory
      infiltrates predominantly consisted of CD68+ MRP14+ macrophages which weakly
      expressed TNF-alpha, a few CD3+ T cells with a prominent IL-10 expression, and
      single CD123+ plasmacytoid dendritic cells. In DM, infiltrates were mainly
      composed of CD3+ CD4+ T cells which expressed IL-10, numerous CD123+ plasmacytoid
      dendritic cells, and CD20+ B cells. The low number of CD68+ macrophages was of
      25F9+ late inflammatory phenotype. Membrane attack complex was expressed in
      necrotic muscle fibers in IMAM and on endomysial capillaries in DM, respectively.
      Thus, in IMAM, the inflammatory reaction markedly differed from DM. These
      observations may lend support to the hypothesis that IMAM and DM are distinct
      with respect to their pathogenesis. Whether, alternatively, these differences in
      the cellular composition of the infiltrates and the cytokine profile rather
      reflect different stages of disease, will require the analysis of a larger
      series.

PMID- 19590881
TI  - The anterior cingulate cortex in autism: heterogeneity of qualitative and
      quantitative cytoarchitectonic features suggests possible subgroups.
AB  - Autism is a behaviorally defined disorder with deficits in social interaction,
      communication, atypical behaviors, and restricted areas of interest. Postmortem
      studies of the brain in autism have shown a broad spectrum of abnormalities in
      the cerebellum and neocortex, involving limbic regions such as anterior cingulate
      cortex (ACC, Brodmann's area 24). Using stereological techniques, we analyzed
      quantitatively cytoarchitectonic subdomains of the ACC (areas 24a, b, c) with
      regard to cell packing density and cell size. Microscopic examination of the ACC
      was also done to identify any neuropathologies. Results showed a significant
      decrease in cell size in layers I-III and layers V-VI of area 24b and in cell
      packing density in layers V-VI of area 24c. Direct comparisons revealed irregular
      lamination in three of nine autism brains and increased density of neurons in the
      subcortical white matter in the remaining cases. Because previous studies have
      suggested that von Economo neurons (VENs) may be altered in autism, a preliminary
      study of their density and size was undertaken. VEN density did not differ
      between autism and control brains overall. However, among the nine autism cases,
      there were two subsets; three brains with significantly increased VEN density and
      the remaining six cases with reduced VEN density compared to controls.
      Collectively, the findings of this pilot study may reflect the known
      heterogeneity in individuals with autism and variations in clinical
      symptomotology. Further neuroanatomic analyses of the ACC, from carefully
      documented subjects with autism, could substantially expand our understanding of
      ACC functions and its role in autism.

PMID- 19590882
TI  - A case of unilateral hypoglossus nerve palsy associated with chordoma in the
      region of clivus.
AB  - We had a rare case of 50-year-old woman with a unilateral hypoglossus nerve palsy
      as a sign of clival chordoma. A computed tomography (CT) scan of the skull base
      showed bone destruction at the anterior part of the foramen magnum and CT scan of
      the neck reveals asymmetrical area at the base of the tongue. Magnetic resonance
      imaging showed a mass at the skull base in the region of the clivus with bone
      destruction in the middle and right side of the clivus. The tumor was biopsied
      through transnasal biopsy from the region of the clivus using a navigation system
      and microscopical surgical technique. Postoperatively, the patient received
      radiotherapy. Surgery is the most effective treatment of chordomas. An endoscopic
      approach provides easy, rapid and direct access to the clivus. A postoperative
      radiation therapy is recommended. A carbon ion radiotherapy is an effective
      treatment for chordomas of the skull base with minimal side effects. Close
      interdisciplinary collaboration between ORL, neuroradiology, pathology and
      oncology is desirable for effective therapy.

PMID- 19590883
TI  - Confocal endomicroscopy: a novel application for imaging of oral and
      oropharyngeal mucosa in human.
AB  - Confocal endomicroscopy is an emerging technique for intravital visualization of
      neoplastic lesions, but its use has so far been limited to the gastrointestinal
      (GI) tract. This study was designed to assess the feasibility of in vivo confocal
      endomicroscopy of different regions of the oropharyngeal mucosa and to evaluate
      different contrast agents. We examined five different regions of the human
      oropharynx in vivo, and images were collected in real time by using a confocal
      laser endoscope as formerly described for the GI tract. Additionally ex vivo
      specimens were examined using a topical contrast agent. Confocal scanning was
      performed at 488-nm illumination for excitation of exogenously applied
      fluorophores (topical acriflavine and intravenous fluorescein). Confocal
      endomicroscopy allowed for visualization of cellular and subcellular structures
      of the anterior human oropharyngeal region. Fluorescein staining yielded
      architectural details of the surface epithelium and also subepithelial layers.
      Images taken at increasing depth beneath the epithelium showed the mucosal
      capillary network. Acriflavine strongly contrasted the cell nuclei of the surface
      epithelium. The findings correlated well with the histology of biopsy specimens.
      This is the first report showing that the use of fluorescence confocal
      endomicroscopy represents a promising method to examine cellular details in vivo
      in different oropharyngeal regions in human.

PMID- 19590884
TI  - Prof. Dr. Gyorgy Lichtenberger (1944-2009), Budapest, Hungary.

PMID- 19590885
TI  - At the right place at the right time: novel CENP-A binding proteins shed light on
      centromere assembly.
AB  - Centromeres, the chromosomal loci that form the sites of attachment for spindle
      microtubules during mitosis, are identified by a unique chromatin structure
      generated by nucleosomes containing the histone H3 variant CENP-A. The apparent
      epigenetic mode of centromere inheritance across mitotic and meiotic divisions
      has generated much interest in how CENP-A assembly occurs and how structurally
      divergent centromeric nucleosomes can specify the centromere complex. Although a
      substantial number of proteins have been implicated in centromere assembly,
      factors that can bind CENP-A specifically and deliver nascent protein to the
      centromere were, thus far, lacking. Several recent reports on experiments in
      fission yeast and human cells have now shown significant progress on this
      problem. Here, we discuss these new developments and their implications for
      epigenetic centromere inheritance.

PMID- 19590886
TI  - Homogeneity in mitochondrial DNA control region sequences in Swedish
      subpopulations.
AB  - In order to promote mitochondrial DNA (mtDNA) testing in Sweden we have typed 296
      Swedish males, which will serve as a Swedish mtDNA frequency database. The tested
      males were taken from seven geographically different regions representing the
      contemporary Swedish population. The complete mtDNA control region was typed and
      the Swedish population was shown to have high haplotype diversity with a random
      match probability of 0.5%. Almost 47% of the tested samples belonged to
      haplogroup H and further haplogroup comparison with worldwide populations
      clustered the Swedish mtDNA data together with other European populations. AMOVA
      analysis of the seven Swedish subregions displayed no significant maternal
      substructure in Sweden (F (ST) = 0.002). Our conclusion from this study is that
      the typed Swedish individuals serve as good representatives for a Swedish
      forensic mtDNA database. Some caution should, however, be taken for individuals
      from the northernmost part of Sweden (provinces of Norrbotten and Lapland) due to
      specific demographic conditions. Furthermore, our analysis of a small sample set
      of a Swedish Saami population confirmed earlier findings that the Swedish Saami
      population is an outlier among European populations.

PMID- 19590888
TI  - Expression of hypoxia-inducible factor-1alpha and -2alpha in human choroidal
      neovascular membranes.
AB  - PURPOSE: Up-regulation of pro-angiogenic cytokine expression occurring secondary
      to hypoxia in physiologic and pathophysiologic conditions is mediated by the
      family of transcription regulators know as hypoxia inducible factors (HIF). The
      present study was undertaken to investigate the expression of HIF occurring in
      human choroidal neovascularization (CNV) and the posterior segment of young and
      old eyes. METHODS: Surgically excised CNV from patients with either age-related
      macular degeneration (AMD; n = 9), punctuate inner choroidopathy (PIC; n = 3) and
      young normal eyes were immunohistochemically probed with monoclonal antibodies
      against HIF-1alpha and -2alpha and compared to that for cell markers specific for
      vascular endothelial cells (CD34), macrophages (CD68), retinal pigment epithelial
      cells (RPE; panel cytokeratins/CK18) and VEGF. Following secondary antibody
      amplification, reactions were visualized with fast red chromogen. RESULTS:
      Cellular immunoreactivity of membranes for HIF-2alpha was strong in eight out of
      nine AMD specimens but it was only weakly positive for HIF-1alpha in five
      specimens. In contrast, two out of three PIC specimens were weakly positive for
      HIF-1alpha but demonstrated no staining for HIF-2alpha. Immunohistochemical
      analysis revealed areas within the CNV membranes that were predominantly
      immunopositive for CD68 and cytokeratin indicating the presence of RPE and/or
      macrophages and that these cells strongly co-localized with the presence of HIF
      and VEGF. No immunochemical co-localization was observed with HIF and the
      endothelial cell marker CD34 in any membranes studied. Normal globes also
      demonstrated HIF-2 positivity to be predominantly localized to the central RPE
      rather than peripheral RPE irrespective of age of donor. CONCLUSIONS: The
      localization of HIF expression supports the concept that hypoxia is a major
      stimulus for the development of submacular wound healing and within this context
      CNV is but one component of this process.

PMID- 19590887
TI  - Mechanical force enhances MMP-2 activation via p38 signaling pathway in human
      retinal pigment epithelial cells.
AB  - BACKGROUND: Rhegmatogenous retinal detachment and proliferative vitreoretinopathy
      (PVR) are eye diseases that are characterized by mechanical stress involving
      stretching of the retinal pigment epithelial (RPE) cells by the vitreous or the
      hyperplastic membranes. Here, we assessed whether mechanical force could change
      the expression of matrix metalloproteinases (MMPs) in RPE cells via the mitogen
      activated protein kinase (MAPK) pathway. METHODS: Collagen-coated magnetite beads
      and magnetic fields were used to apply tensile forces to cultured RPE cells at
      focal adhesions. Activation of the MAPK, including extracellular signal-regulated
      protein kinase (ERK), c-jun N-terminal kinase (JNK), and p38 were determined over
      a time course from 5 to 30 min by Western-blot analysis. Activation of p38 was
      also tested using immunofluorescence staining. The mRNA levels of MMP-2, MMP-9,
      tissue inhibitor of MMP (TIMP)-2 and fibronectin (FN) were analyzed by RT-PCR.
      Active MMP-2 and MMP-9 were demonstrated by zymography. MMP-2 secretion was
      evaluated by enzyme immunoassay. RESULTS: Stimulation of RPE cells with
      mechanical stress did not change the total protein expression of the MAPK
      proteins ERK, JNK, and p38. However, of the three kinases, only active p38 showed
      an increased protein expression which was also shown by a 2.8-fold increase in
      immunofluorescence staining at 5 min following mechanical stress stimulation.
      This increase in active p38 expression was blocked by treating the cells with the
      p38 inhibitor SB203580. FN mRNA increased 2.4-fold at 15 min and MMP-2 mRNA
      increased 2.1-fold at 4 h. MMP-2 secretion increased 1.5-fold at 4 h and 1.9-fold
      at 12 h. The expression of MMP-2 and FN, and the activation and secretion of MMP
      2, were inhibited in the presence of SB203580. The mRNA expression of MMP-9 and
      TIMP-2 did not change throughout. CONCLUSIONS: This study shows that mechanical
      stress upregulates MMP-2 and FN expression through activation of the p38 pathway.
      The increase in MMP-2 levels evoked by mechanical force may contribute to the
      remodeling of the extracellular matrix around RPE cells, weakening the
      interlinkage and membrane attachment between RPE cells, and facilitate cellular
      migration.

PMID- 19590889
TI  - Physical and psychosocial work stressors, health-related control beliefs and work
      ability: cross-sectional findings from the German Sociomedical Panel of
      Employees.
AB  - PURPOSE: The aim of this paper was to analyse the cross-sectional associations
      between work-related stressors and work ability and to investigate moderator-type
      effects of internal health-related control beliefs (IHRCB). METHODS: A total of
      1,348 working men and women aged 30-59 years from the baseline survey of the
      German Sociomedical Panel of Employees were included in the analyses. Work
      ability was assessed by the Work Ability Index (WAI). Work-related stressors were
      defined as physical demands and in terms of the demand-control model and the
      effort-reward imbalance model. RESULTS: Restrictions of work ability were
      explained independently by physical demands and by work stress exposure due to
      high demand and low control and due to effort-reward imbalance. These effects
      were more serious for workers with low IHRCB than those with high IHRCB.
      CONCLUSIONS: IHRCB are an important personal resource that might moderate the
      effect of work-related stressors on work ability. However, longitudinal analyses
      are required to confirm these results.

PMID- 19590890
TI  - Imaging for primary hyperparathyroidism--an evidence-based analysis.
AB  - OBJECTIVE: Imaging in patients with primary hyperparathyroidism has been proven
      difficult. During the last decade, sestamibi scintigraphy and ultrasound (US)
      have been used with various success. The importance of these procedures has risen
      since minimal invasive parathyroid (MIP) surgery also has developed, and it is
      claimed that preoperative localization usually is needed before embarking on such
      a procedure. METHODS: We have scanned the most recent literature in this matter
      in order to identify evidence, using commonly accepted grading, and also
      concluded a number of recommendations. RESULTS AND CONCLUSIONS: We found evidence
      at level III leading to recommendations at grade B, that sestamibi scintigraphy
      is a recommended first test, but that US by an experienced investigator may be an
      alternative. MIP may be performed when both tests are concordant, and in case of
      only one test being positive, unilateral exploration and use of intraoperative
      PTH measurements are recommended. Bilateral neck exploration is used when both
      tests are negative. For reoperative procedures, repeat investigations are
      recommended, but also to use US-guided fine needle aspiration and PTH
      measurements as well as venous sampling. However, for reoperative procedures, the
      level of evidence is weaker-level IV, but recommendations still at grade B.

PMID- 19590893
TI  - Phase II study of Rituximab combined with THP-COP as first-line therapy for
      patients younger than 70 years with diffuse large B cell lymphoma.
AB  - INTRODUCTION: We previously described the effectiveness of the THP-COP regimen
      comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP),
      vincristine and prednisolone in patients with diffuse large B-cell lymphoma
      (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than
      doxorubicin. However, that study was completed before rituximab was introduced
      into clinical practice. We conducted a phase II study to determine the
      effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL.
      PATIENTS: Six to 8 courses of the regimen were administered every 2 weeks in 48
      patients who were younger than 70 years. RESULTS: The complete remission rate was
      92%, the 3-year overall survival rate was 83% and 3-year progression free
      survival rate was 74%. No deaths were associated with the treatment regimen.
      CONCLUSION: We conclude that R-THP-COP regimen is very effective against DLBCL.
      The results of our study urge randomized trials of R-CHOP and R-THP-COP among
      patients with CD20+ DLBCL.

PMID- 19590891
TI  - Intraoperative adjuncts in surgery for primary hyperparathyroidism.
AB  - PURPOSE: This paper is a review of the evidence base to produce recommendations
      for the use of intraoperative parathyroid hormone (PTH), radioguided
      parathyroidectomy (RGP), methylene blue (MB), frozen section, and intraoperative
      neuromonitoring during surgery for primary hyperparathyroidism (PHPT). MATERIALS
      AND METHODS: A Medline keyword search of English-language articles led to the
      production of a draft document, subsequently revised by committee, containing
      levels of evidence and the grading of recommendations as proposed by the Agency
      for Healthcare Research and Quality. RESULTS: Literature review provides the
      basis for clear recommendations on the use of intraoperative PTH at surgery for
      PHPT. There is little evidence to support the use of RGP, MB, routine frozen
      section, and intraoperative neuromonitoring.

PMID- 19590894
TI  - Application of serial analysis of gene expression to the study of human genetic
      disease.
AB  - Sequence tag analysis using serial analysis of gene expression (SAGE) is a
      powerful strategy for the quantitative analysis of gene expression in human
      genetic disorders. SAGE facilitates the measurement of mRNA transcripts and
      generates a non-biased gene expression profile of normal and pathological disease
      tissue. In addition, the SAGE technique has the capacity of detecting the
      expression of novel transcripts allowing for the identification of previously
      uncharacterised genes, thus providing a unique advantage over the traditional
      microarray-based approach for expression profiling. The technique has been
      successful in providing pathological gene expression profiles in a number of
      common genetic disorders including diabetes, cardiovascular disease, Parkinson
      disease and Down syndrome. When combined with next generation sequencing
      platforms, SAGE has the potential to become a more powerful and sensitive
      technique making it more amenable for diagnostic use. This review will therefore
      discuss the application of SAGE to several common genetic disorders and will
      further evaluate its potential use in diagnosing human genetic disease.

PMID- 19590896
TI  - Direct and indirect effects of understorey bamboo shape tree regeneration niches
      in a mixed temperate forest.
AB  - Plant cover plays a major role in shaping the nature of recruitment microsites
      through direct (resource mediated) and indirect (consumer mediated) interactions.
      Understorey plants may differentially affect seedling establishment, thus
      contributing to regeneration-niche separation among canopy tree species. We
      examined patterns of early tree seedling survival resulting from interactive
      effects of understorey bamboo (Chusquea culeou) and resident consumers in a mixed
      temperate Patagonian forest, Argentina. Newly germinated seedlings of Nothofagus
      dombeyi and Austrocedrus chilensis were planted in bamboo thickets and non-bamboo
      patches, with or without small-vertebrate exclosures. We found species-specific
      patterns of seedling survival in relation to bamboo cover. Nothofagus survival
      was generally low but increased under bamboo, irrespective of cage treatment.
      Desiccation stress accounted for most Nothofagus mortality in open, non-bamboo
      areas. In contrast, Austrocedrus survival was highest in non-bamboo microsites,
      as most seedlings beneath bamboo were killed by small vertebrates through direct
      consumption or non-trophic physical damage. There was little evidence for a
      negative impact of bamboo on tree seedling survival attributable to resource
      competition. The balance of simultaneous positive and negative interactions
      implied that bamboo presence facilitated Nothofagus early establishment but
      inhibited Austrocedrus recruitment via apparent competition. These results
      illustrate the potential for dominant understorey plants to promote microsite
      segregation during early stages of recruitment between tree seedlings having
      different susceptibilities to water stress and herbivory. We recognise, however,
      that patterns of bamboo-seedling interactions may be conditional on moisture
      levels and consumer activity during establishment. Hence, both biotic and abiotic
      heterogeneity in understorey environments should be incorporated into conceptual
      models of regeneration dynamics and tree coexistence in forest communities.

PMID- 19590895
TI  - Genetic influence on variation in serum uric acid in American Indians: the strong
      heart family study.
AB  - Hyperuricemia is associated with the metabolic syndrome, gout, renal and
      cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of
      individuals in the strong heart family study (SHFS) have high serum uric acid
      levels. The aim of this study was to investigate the genetic determinants of
      serum uric acid variation in American Indian participants of the SHFS. A variance
      component decomposition approach (implemented in SOLAR) was used to conduct
      univariate genetic analyses in each of three study centers and the combined
      sample. Serum uric acid was adjusted for age, sex, age x sex, BMI, estimated
      glomerular filtration rate, alcohol intake, diabetic status and medications.
      Overall mean +/- SD serum uric acid for all individuals was 5.14 +/- 1.5 mg/dl.
      Serum uric acid was found to be significantly heritable (0.46 +/- 0.03 in all
      centers, and 0.39 +/- 0.07, 0.51 +/- 0.05, 0.44 +/- 0.06 in Arizona, Dakotas and
      Oklahoma, respectively). Multipoint linkage analysis showed significant evidence
      of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm
      of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on
      chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate
      gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12)
      that encodes a major uric acid transporter URAT1. These results show a
      significant genetic influence and a possible role for one or more genes on
      chromosomes 1 and 11 on the variation in serum uric acid in American Indian
      populations.

PMID- 19590897
TI  - Do centennial tree-ring and stable isotope trends of Larix gmelinii (Rupr.) Rupr.
      indicate increasing water shortage in the Siberian north?
AB  - Tree-ring width of Larix gmelinii (Rupr.) Rupr., ratios of stable isotopes of C
      (delta(13)C) and O (delta(18)O) of whole wood and cellulose chronologies were
      obtained for the northern part of central Siberia (Tura, Russia) for the period
      1864-2006. A strong decrease in the isotope ratios of O and C (after atmospheric
      delta(13)C corrections) and tree-ring width was observed for the period 1967
      2005, while weather station data show a decrease in July precipitation, along
      with increasing July air temperature and vapor pressure deficit (VPD).
      Temperature at the end of May and the whole month of June mainly determines tree
      radial growth and marks the beginning of the vegetation period in this region. A
      positive correlation between tree-ring width and July precipitation was found for
      the calibration period 1929-2005. Positive significant correlations between C
      isotope chronologies and temperatures of June and July were found for whole wood
      and cellulose and negative relationships with July precipitation. These
      relationships are strengthened when the likely physiological response of trees to
      increased CO(2) is taken into account (by applying a recently developed
      delta(13)C correction). For the O isotope ratios, positive relationships with
      annual temperature, VPD of July and a negative correlation with annual
      precipitation were observed. The delta(18)O in tree rings may reflect annual
      rather than summer temperatures, due to the late melting of the winter snow and
      its contribution to the tree water supply in summer. We observed a clear change
      in the isotope and climate trends after the 1960s, resulting in a drastic change
      in the relationship between C and O isotope ratios from a negative to a positive
      correlation. According to isotope fractionation models, this indicates reduced
      stomatal conductance at a relatively constant photosynthetic rate, as a response
      of trees to water deficit for the last half century in this permafrost region.

PMID- 19590898
TI  - Determinants and consequences of interspecific body size variation in
      tetraphyllidean tapeworms.
AB  - Tetraphyllidean cestodes are cosmopolitan, remarkably host specific, and form the
      most speciose and diverse group of helminths infecting elasmobranchs (sharks,
      skates and rays). They show substantial interspecific variation in a variety of
      morphological traits, including body size. Tetraphyllideans represent therefore,
      an ideal group in which to examine the relationship between parasite body size
      and abundance. The individual and combined effects of host size, environmental
      temperature, host habitat, host environment, host physiology, and host type (all
      likely correlates of parasite body size) on parasite length were assessed using
      general linear model analyses using data from 515 tetraphyllidean cestode species
      (182 species were included in analyses). The relationships between
      tetraphyllidean cestode length and intensity and abundance of infection were
      assessed using simple linear regression analyses. Due to the contrasting
      morphologies between shark and batoid hosts, and contrasting physiologies between
      sharks of the Lamnidae family and other sharks, analyses were repeated in
      different subsets based on host morphology and physiologies ("sharks" vs.
      batoids) to determine the influence of these variables on adult tetraphyllidean
      tapeworm body size. Results presented herein indicate that host body size,
      environmental temperature and host habitat are relatively important variables in
      models explaining interspecific variations in tetraphyllidean tapeworm length. In
      addition, a negative relationship between tetraphyllidean body size and intensity
      of infection was apparent. These results suggest that space constraints and
      ambient temperature, via their effects on metabolism and growth, determine adult
      tetraphyllidean cestode size. Consequently, a trade-off between size and numbers
      is possibly imposed by external forces influencing host size, hence limiting
      physical space or other resources available to the parasites.

PMID- 19590899
TI  - Trade-offs in plant responses to herbivory influence trophic routes of production
      in a freshwater wetland.
AB  - Responses of aquatic macrophytes to leaf herbivory may differ from those
      documented for terrestrial plants, in part, because the potential to maximize
      growth following herbivory may be limited by the stress of being rooted in
      flooded, anaerobic sediments. Herbivory on aquatic macrophytes may have ecosystem
      consequences by altering the allocation of nutrients and production of biomass
      within individual plants and changing the quality and quantity of aboveground
      biomass available to consumers or decomposers. To test the effects of leaf
      herbivory on plant growth and production, herbivory of a dominant macrophyte,
      Nymphaea odorata, by chrysomelid beetles and crambid moths was controlled during
      a 2-year field experiment. Plants exposed to herbivory maintained, or tended to
      increase, biomass and aboveground net primary production relative to controls,
      which resulted in 1.5 times more aboveground primary production entering the
      detrital pathway of the wetland. In a complementary greenhouse experiment, the
      effects of simulated leaf herbivory on total plant responses, including biomass
      and nutrient allocation, were investigated. Plants in the greenhouse responded to
      moderate herbivory by maintaining aboveground biomass relative to controls, but
      this response occurred at the expense of belowground growth. Results of these
      studies suggest that N. odorata may tolerate moderate levels of herbivory by
      reallocating biomass and resources aboveground, which in turn influences the
      quantity, quality and fate of organic matter available to herbivores and
      decomposers.

PMID- 19590901
TI  - Enhanced antibody production following intermediate addition based on flux
      analysis in mammalian cell continuous culture.
AB  - Generally, mammalian cells utilize glucose and glutamine as primary energy
      sources. To investigate the effect of energy sources on metabolic fluxes and
      antibody production, glucose- or glutamine-limited serum-free continuous culture
      of hybridoma 3A21 cells, which produce anti-ribonuclease A antibody, was carried
      out. The cell volume and dry cell weight were evaluated under various steady
      state conditions. The specific consumption and production rates were evaluated on
      the basis of dry cell weight. On the basis of these results, the fluxes of the
      metabolic pathway were calculated. It was found that increasing the specific
      growth rate causes the specific ATP and antibody production rates to decrease.
      The fluxes between malate and pyruvate also decreased with the increase in
      specific growth rate. To increase the ATP production rate under steady-state
      conditions by the enhancement of fluxes between malate and pyruvate, the reduced
      metabolic fluxes were increased by an intermediate (pyruvate, malate, and
      citrate) addition. As a result, higher specific ATP and antibody production rates
      were achieved following the intermediate addition at a constant dilution rate.

PMID- 19590900
TI  - Food level and sex shape predator-induced physiological stress: immune defence
      and antioxidant defence.
AB  - Despite the potential impact on prey fitness and predator-prey interactions, most
      studies of predation risk ignore physiological responses and their dependence
      upon food level and sex. Therefore, we reared male and female larvae of the
      damselfly Lestes viridis under predator stress (dragonfly larvae) at high and low
      food levels, and subsequently scored for important variables of insect immune
      defence (i.e. phenoloxidase) and antioxidant defence [i.e. superoxide dismutase,
      and catalase (CAT)]. Under predation risk, larvae did not decrease growth rate or
      immune defence, and only slightly reduced food intake in the high food treatment,
      probably because of time stress, i.e. little time available to complete the
      larval development. However, larvae facing predator stress did show an
      upregulation of antioxidant enzymes. This upregulation was dependent upon food
      level for CAT and both food level and sex for SOD, consistent with energetic
      constraints and sex differences in the link between longevity and adult fitness.
      Our results illustrate that predator stress can influence life history,
      behavioural and physiological responses differentially and in a context-dependent
      way. This implies that non-consumptive physiological effects of predators on
      their prey show independent yet similar complexities in behavioural and life
      history response variables. In general, our results advocate that mechanistic
      studies on predator-prey interactions may benefit from including physiological
      variables.

PMID- 19590902
TI  - Prophylaxis of catheter-related bacteremia using tissue plasminogen activator
      tobramycin locks.
AB  - This retrospective study was designed to investigate the effectiveness of tissue
      plasminogen activator-tobramycin antibiotic lock solutions (TPA/tobra ABLs) for
      prophylaxis of catheter-related bacteremia (CRB) in high-risk children on long
      term hemodialysis. During the first 6 months (Era 1), the high-risk group was
      defined. These patients received TPA/tobra ABL prophylaxis after every
      hemodialysis treatment for the next 6 months (Era 2). The prophylaxis regimen was
      applied once a week for the third 6-months period (Era 3). Primary endpoints were
      CRB and infection-free catheter survival. There were 16,412 catheter days, and 95
      cases of CRB in 43 children. The incidence of CRB was 5.8/1,000 catheter days.
      Significant decrease in the incidence of CRB was observed when prophylactic
      TPA/tobra ABL was used in the high-risk group (P = 0.0201). There was a tendency
      for less CRB when prophylactic ABL was applied after every hemodialysis session
      compared with once a week (P = 0.0947). The catheters in the high-risk group had
      shorter survival times than those in the average-risk group in Era 1 (P <
      0.0001). However, both the overall and infection-free survival of the catheters
      in the high-risk group significantly improved while the patients were receiving
      TPA/tobra ABL prophylaxis, becoming similar to the outcomes of the catheters in
      the average-risk group and exhibiting statistically non-significant differences
      (P = 0.5571 and P = 0.9711, respectively). In conclusion, the TPA/tobra ABLs may
      effectively reduce the rate of CRB, and this may prolong both the overall and
      infection-free survival times of the catheters in the high-risk group.

PMID- 19590904
TI  - Development of the MASCC Teaching Tool for Patients Receiving Oral Agents for
      Cancer.
AB  - BACKGROUND: Oral agents for cancer treatment commonly are prescribed throughout
      the world. Since oral agents usually are self-administered or administered by lay
      caregivers, patient education is vital to help ensure that the oral agents are
      being stored, handled, and taken correctly. When oral agents are taken as
      prescribed and patients are well informed about signs and symptoms to report,
      patient outcomes are optimized. Patient education varies globally; consequently,
      there is a need for a consistent and comprehensive approach to educate patients
      about oral cancer treatment. GOAL OF WORK: To create a teaching tool to be used
      with patients receiving oral cancer agents for worldwide use. MATERIALS AND
      METHODS: Six oncology nurse experts conducted a literature review and convened as
      an expert panel to draft a teaching tool for patients receiving oral cancer
      agents. The tool includes key assessment questions, generic education discussion
      points, drug-specific education, and evaluation questions to help ensure that
      patients/caregivers understand the information provided. Eighteen healthcare
      providers from 15 countries reviewed the tool for clarity and usefulness in
      practice by scoring each item in the teaching tool on a 0-10 scale ("0 = not at
      all to "10" = most clear/useful"). Items that scored 5 or below required
      comments. At the Multinational Association for Supportive Care in Cancer (MASCC)
      Symposium in 2008, the healthcare providers who reviewed the teaching tool met
      with the oncology nurse experts who had developed the tool to review the item
      scores and revise the tool as necessary. RESULTS: All items on the teaching tool
      received high scores, with the exception of items on refilling prescriptions and
      insurance issues, which vary from country to country. There was consensus that
      the MASCC Teaching Tool for Patients Receiving Oral Agents for Cancer was ready
      to be used and further evaluated in clinical practice. CONCLUSIONS: The MASCC
      Teaching Tool for Patients Receiving Oral Agents for Cancer is an available
      resource to assist healthcare providers assess and teach patients about oral
      cancer treatment.

PMID- 19590903
TI  - [Suggestion for a classification of odontalgias].
AB  - BACKGROUND: Toothache prevalence in the overall population is considerable.
      However, for clinical purposes, the classification schemes available do not
      appear to be sufficiently sophisticated. Moreover, not all known forms of dental
      pain are considered. A refined classification that meets current standards is
      therefore introduced. To facilitate diagnosis, the characteristic features of the
      various types of odontalgia are summarized. RESULTS: The new classification
      differentiates among seven different origins of pain: 1. dentinal pain
      (originating from the pulpal tissues), 2. pulpal pain (originating from the
      pulpal tissues), 3. periodontal pain, 4. alveolar-osseous pain, 5. atypical
      odontalgia, 6. heterotopic dental pain, 7. odontalgia associated with primary
      psychosocial factors. CONCLUSIONS: In our opinion, the proposed classification
      differentiates among the different forms of odontalgia more precisely than all
      previous ones. However, its viability and advantages over other available
      classification schemes still need to be verified in daily practice.

PMID- 19590905
TI  - Painful camptocormia: the relevance of shaking your patient's hand.
AB  - Camptocormia is an abnormal posture with marked flexion of thoracolumbar spine
      that abates in the recumbent position. Camptocormia has been described in various
      neurological (Parkinsonism), muscular (myopathy), psychogenic or orthopedic
      disorders. There are several hypotheses that can explain this impaired posture
      but they are usually related to the concomitant pathologies. We report the first
      case of a patient with confirmed myotonic dystrophy addressed to our medical
      center for impaired posture who underwent extensive medical exams and
      explorations because of a myotonic hand. Axial weakness and muscle atrophy,
      validated by CT-scan imaging, are discussed independent of the concomitant
      pathology (Parkinson, myopathy).

PMID- 19590906
TI  - Severe restrictive lung disease and vertebral surgery in a pediatric population.
AB  - The aim of this study is to describe the outcome of surgical treatment for
      pediatric patients with forced vital capacity (FVC) <40% and severe vertebral
      deformity. Few studies have examined surgical treatment in these patients, who
      are considered to be at a high risk because of their pulmonary disease, and in
      whom preoperative tracheostomy is sometimes recommended. Inclusion criteria
      include FVC <40%, age <19 years and diagnosis of scoliosis. The retrospective
      study of 24 patients with severe restrictive lung disease, who underwent spinal
      surgery. Variables studied were age and gender, pre- and postoperative spirometry
      (FVC, FEV1, FEV1/FVC), preoperative, postoperative and late use of non-invasive
      ventilation (BiPAP) or mechanical ventilation, associated multidisciplinary
      treatment, type and location of the curve, pre- and postoperative curve values,
      type of vertebral fusion, intra- and postoperative complications, duration of
      intensive care unit (ICU) stay and length of postoperative hospitalization. Mean
      age was 13 years (9-19) of which 13 were males and 11 females. Mean follow-up was
      32 months (24-45). The etiology was neuromuscular in 17 patients and other
      etiologies in 7 patients. Mean preoperative FVC was 26% (13-39%). Eight patients
      had preoperative home BiPAP, 15 preoperative in-hospital BiPAP, and 2
      preoperative mechanical ventilation. Nine patients had preoperative nutritional
      support. Preoperative curve value of the deformity was 88 degrees (40 degrees 
      129 degrees ). Nineteen patients with posterior fusion alone and 5 with anterior
      and posterior fusion were found. Mean duration of ICU stay was 5 days (1-21).
      Total postoperative hospital stay was 17 days (7-33). Ventilatory support in the
      immediate postoperative includes 16 patients requiring BiPAP and 2 volumetric
      ventilation. None of the patients required a tracheostomy. The intraoperative
      complications include one death due to acute heart failure; immediate
      postoperative, four respiratory failures (2 required ICU readmission) and one
      respiratory infection; and other minor complications occurred in six patients.
      Overall, 58% of patients had complications. Percentage of angle correction was
      56%. After a follow-up of 30 months, FVC was 29% (13-50%). In conclusion,
      corrective scoliosis surgery in pediatric patients with severe restrictive lung
      disease is well tolerated, but the management of this population requires
      extensive experience with the vertebral surgery involved, and a multidisciplinary
      approach that includes pulmonologists, nutritionists and anesthesiologists.
      Currently, there is no indication for routine preoperative tracheostomy.

PMID- 19590907
TI  - Comparison of human dental follicle cells (DFCs) and stem cells from human
      exfoliated deciduous teeth (SHED) after neural differentiation in vitro.
AB  - Dental stem cells from human exfoliated deciduous teeth (SHED) and dental
      follicle cells (DFCs) are neural crest-derived stem cells from human dental
      tissues. Interestingly, SHED and DFCs can successfully differentiate into neuron
      like cells. We hypothesized that SHED and DFCs have the same neural cell
      differentiation potentials. To evaluate neural cell differentiation, we
      cultivated SHED and DFCs in four different serum-replacement media (SRMs) and
      analyzed cell morphology, cell proliferation, and gene expression patterns before
      and after differentiation. In a standard cell culture medium, SHED and DFCs have
      not only similar cell morphologies, but they also have similar gene expression
      patterns for known stem cell markers. However, only SHED expressed the neural
      stem cell marker Pax6. After cultivation in SRMs, cell proliferations of DFCs and
      SHED were reduced and the cell morphology was spindle-like with long processes.
      However, differentiated DFCs and SHED had different neural cell marker expression
      patterns. For example, gene expression of the late neural cell marker microtubule
      associated protein 2 was upregulated in DFCs and downregulated in SHED in SRM
      with the B27 supplement. In contrast, SHED formed neurosphere-like cell clusters
      in SRM with the B27 supplement, epidermal growth factor, and fibroblast growth
      factor-2. Moreover, SHED differentially expressed the glial cell marker glial
      fibrillary acidic protein, which in contrast was weakly or not expressed in DFCs.
      In conclusion, SHED and DFCs have different neural differentiation potentials
      under the same cell culture conditions.

PMID- 19590908
TI  - Dentofacial characteristics of patients with hypodontia.
AB  - This study aims to identify distinctive dentofacial characteristics of hypodontia
      patients. For this purpose, 189 young hypodontia patients (cases) were divided
      into subgroups, based on criteria from literature. Normalised differences between
      cases and controls were calculated for various parameters of dentofacial form.
      Subsequently, cluster analysis was applied to disclose subsets of hypodontia
      patients with distinctive dentofacial features. The ANB angle, interincisal angle
      and lower anterior face height were consistently significantly different amongst
      the subsets. Four clusters of patients with an increasing number of missing teeth
      and distinctive dentofacial characteristics could be identified. Patients in
      cluster 1 display a high-angle facial pattern. Patients in clusters 2 and 3
      exhibit markable dentoalveolar characteristics (a relatively small and a large
      interincisal angle, respectively). Patients in cluster 4 exhibited notable
      sagittal-skeletal discriminative features predominantly because of a retrognathic
      maxilla. The smallest nasolabial angle and lower anterior face height were seen
      in this cluster. It is concluded that the anterior-posterior relationship between
      the jaws, the interincisal angle and the lower anterior face height are
      discriminative parameters of dentofacial form in hypodontia patients. Patients
      with hypodontia can be clustered in four groups, each with distinctive vertical
      skeletal, dentoalveolar and sagittal-skeletal characteristics. This
      categorisation of patients with hypodontia into meaningful groups may be useful
      for treatment planning, interdisciplinary communication and as a means of
      identifying groups of patients that qualify for reimbursement of costs. Other
      dental factors should be appreciated as well during restorative clinical decision
      making in patients with hypodontia.

PMID- 19590909
TI  - In silico QSAR studies of anilinoquinolines as EGFR inhibitors.
AB  - Members of the epidermal growth factor receptor (EGFR) family of proteins are
      frequently overactive in solid tumors. A relatively new therapeutic approach to
      inhibit the kinase activity is the use of ATP-competitive small molecules. In
      silico techniques were employed to identify the key interactions between
      inhibitors and their protein receptors. A series of EGFR inhibitory
      anilinoquinolines was studied within the framework of hologram quantitative
      structure activity relationship (HQSAR), density functional theory (DFT)-based
      QSAR, and three-dimensional (3D) QSAR (CoMFA/CoMSIA). The HQSAR analysis implied
      that substitutions at certain sites on the inhibitors play an important role in
      EGFR inhibition. DFT-based QSAR results suggested that steric and electronic
      interactions contributed significantly to the activity. Ligand-based 3D-QSAR and
      receptor-guided 3D-QSAR analyses such as CoMFA and CoMSIA techniques were carried
      out, and the results corroborated the previous two approaches. The 3D QSAR models
      indicated that steric and hydrophobic interactions are dominant, and that
      substitution patterns are an important factor in determining activity. Molecular
      docking was helpful in identifying a bioactive conformer as well as a plausible
      binding mode. The docked geometry-based CoMFA model with steric and electrostatic
      fields effect gave q(2) = 0.66, r(2) = 0.94 with r(2) (predictive) = 0.72.
      Similarly, CoMSIA with hydrophobic field gave q(2) = 0.59, r(2) = 0.85 with r(2)
      (predictive) = 0.63. Bulky groups around site 3 of ring "C", and hydrophilic and
      bulky groups at position 6 of ring "A" are desirable, with a hydrophobic and
      electron-donating group at site 7 of ring "A" being helpful. Accordingly,
      potential EGFR inhibitors may be designed by modification of known inhibitors.

PMID- 19590911
TI  - Segregation by thermal diffusion in moderately dense granular mixtures.
AB  - A theory based on a solution of the inelastic Enskog equation that goes beyond
      the weak dissipation limit is used to determine the thermal diffusion factor of a
      binary granular mixture under gravity. The Enskog equation that aims to describe
      moderate densities neglects velocity correlations but retains spatial
      correlations arising from volume exclusion effects. As expected, the thermal
      diffusion factor provides a segregation criterion that shows the transition
      between the Brazil-nut effect (BNE) and the reverse Brazil-nut effect (RBNE) by
      varying the parameters of the system (masses, sizes, composition, density and
      coefficients of restitution). The form of the phase diagrams for the BNE/RBNE
      transition is illustrated in detail in the tracer limit case, showing that the
      phase diagrams depend sensitively on the value of gravity relative to the thermal
      gradient. Two specific situations are considered: i) absence of gravity, and ii)
      homogeneous temperature. In the latter case, after some approximations, our
      results are consistent with previous theoretical results derived from the Enskog
      equation. Our results also indicate that the influence of dissipation on thermal
      diffusion is more important in the absence of gravity than in the opposite limit.
      The present analysis, which is based on a preliminary short report of the author
      (Phys. Rev. E 78, 020301(R) (2008)), extends previous theoretical results derived
      in the dilute limit case.

PMID- 19590910
TI  - Orthodontic or surgically assisted rapid maxillary expansion.
AB  - PURPOSE: The purpose of this study was to present, compare, and discuss the
      techniques for rapid maxillary expansion. DISCUSSION: The isolated transverse
      maxillary deficiency can be treated either orthodontically or surgically with
      rapid palatal expansion. In children and adolescents, conventional orthodontic
      rapid maxillary expansion has been successful when used before sutural closure.
      On the other hand, in skeletally mature patients, the possibility of successful
      maxillary expansion decreases as sutures close and the resistance to mechanical
      forces increases. CONCLUSIONS: The selection of an expansion technique depends on
      a number of factors. It is more likely to advocate surgery as the patient's age,
      transverse needs, or acceptance of the idea of surgery increases.

PMID- 19590912
TI  - Acceleration of FEM-based transfer matrix computation  for forward and inverse
      problems of electrocardiography.
AB  - The distributions of transmembrane voltage (TMV) within the cardiac tissue are
      linearly connected with the patient's body surface potential maps (BSPMs) at
      every time instant. The matrix describing the relation between the respective
      distributions is referred to as the transfer matrix. This matrix can be employed
      to carry out forward calculations in order to find the BSPM for any given
      distribution of TMV inside the heart. Its inverse can be used to reconstruct the
      cardiac activity non-invasively, which can be an important diagnostic tool in the
      clinical practice. The computation of this matrix using the finite element method
      can be quite time-consuming. In this work, a method is proposed allowing to speed
      up this process by computing an approximate transfer matrix instead of the
      precise one. The method is tested on three realistic anatomical models of real
      world patients. It is shown that the computation time can be reduced by 50%
      without loss of accuracy.

PMID- 19590915
TI  - [Can we influence the progression of chronic kidney disease?].
AB  - Chronic renal failure does not only involve the risk for the patient of becoming
      dependent on hemodialysis, but also increases the risk of premature death due to
      cardiovascular events. In most renal diseases, progressive chronic loss of renal
      function develops once a critical extent of renal damage has occurred,
      independent of the course of the underlying renal disease. The key factors
      driving the progressive loss of renal function are, apart from the underlying
      nephrological disease, arterial hypertension and diabetes mellitus. The loss of
      renal function is also promoted by other factors, such as increased intake of
      dietary proteins, chronic inflammation, smoking, and anemia. With the help of a
      multimodal therapeutic concept, the progression of chronic renal failure can be
      delayed effectively. This approach comprises strict blood pressure control with a
      target blood pressure of 130/80 mmHg in patients with micro-albuminuria and of
      120/75 mmHg in patients with proteinuria of >1 g/d. The preferred drugs for the
      treatment of hypertension are ACE inhibitors and angiotensin receptor blockers.
      In diabetics with renal insufficiency, target HbA1c levels below 7% are to be
      aimed for. Dietary protein intake should be restricted to 0.8-1 g/kg body
      weight/d. Additional therapeutic targets include nicotine abstinence, early
      treatment of renal anemia, weight reduction, and, if indicated, lipid-lowering
      therapy.

PMID- 19590919
TI  - Transcatheter closure of multi-hole perimembranous VSD with aneurysm: 3-year
      follow-up study.
AB  - The majority of ventricular septal defects (VSDs) are perimembranous, accounting
      for 75-80% of all VSDs. The objective of this study was to investigate occluder
      selection and transcatheter closure technique for multi-hole perimembranous VSD
      with aneurysm, and to evaluate clinical efficacy and safety. Patients with multi
      hole VSDs and aneurysm (n = 64) were selected for the procedure using
      transthoracic echocardiography. Double-disc symmetrical, small-waist double-disc
      asymmetrical and zero eccentricity occluders were selected based on left
      ventricular angiography. The closure was successful in 63 of 64 patients (98%).
      The double-disc symmetrical occluder was used in 16 cases, the small-waist double
      disc asymmetrical occluder in 42 cases, and the zero eccentricity occluder in 8
      cases (2 occluder types were used in 2 cases). Fifteen minutes after the
      procedure, 52 cases had no residual shunt and 12 had a trace amount of residual
      shunt. The residual shunt disappeared in five cases 5-7 days post procedure, with
      a trace amount of shunt remaining in seven cases. Transient conduction
      abnormalities related to the procedure occurred in six patients; however, none
      required permanent pacemaker implantation. At the 1-month, 6-month, 1-year, 2
      year, and 3-year follow-up visits, echocardiography indicated that the position
      of the occluders was fixed, and there were no complications including residual
      shunt, newly developed atrioventricular block, thromboembolism, or bacterial
      endocarditis. The study results indicate that left ventricular angiography is
      useful in selecting the most appropriate device for transcatheter closure of
      multi-hole perimembranous VSD with aneurysm. The transcatheter closure procedure
      is safe and effective with little residual shunt and no major complications for
      up to 3 years of follow-up.

PMID- 19590920
TI  - MRI and contrast enhanced MR angiography in a patient with right aortic arch and
      aberrant left subclavian artery.

PMID- 19590914
TI  - [Unstable shoulder dislocation].
AB  - Shoulder dislocations are a frequent event and the severity is often
      underestimated. A thorough clinical investigation and adapted imaging diagnostics
      are able to detect age-dependent injury patterns. A biphasic conservative
      treatment keeping the arm in a neutral to mild external rotation for 3 weeks has
      proven to be most effective and should be followed by an intensive physiotherapy.
      Nevertheless, conservative treatment protocols show unacceptable recurrence rates
      particularly in young men active in sport, therefore, surgical stabilisation is
      recommended. In the past open procedures were accepted as the gold standard, but
      today arthroscopic Bankart repair using suture anchors shows comparable
      recurrence rates. However, the clinical outcome with respect to the shoulder
      function is much better without compromising the subscapularis muscle.

PMID- 19590921
TI  - Delayed and restricted expression of UAS-regulated GFP gene in early transgenic
      zebrafish embryos by using the GAL4/UAS system.
AB  - A stable Tg(UAS:GFP) zebrafish line was generated and crossed with Tg(hsp70:GAL4)
      line, in which the GAL4 gene is under the control of an inducible zebrafish
      promoter derived from the heat shock 70 protein gene (hsp70). The dynamic green
      fluorescent protein (GFP) expression in early zebrafish embryos in the GAL4/UAS
      binary system was then investigated. We found that, at early developmental
      stages, expression of GFP effector gene was restricted and required a long
      recovery time to reach a detectable level. At later developmental stage (after 2
      days postfertilization), GFP could be activated in multiple tissues in a shorter
      time, apparently due to a higher level of GAL4 messenger RNA induction. It
      appears that the type of tissues expressing GFP was dependent on whether they had
      been developed at the time of heat shock. Therefore, the delayed and restricted
      transgene expression should be taken into consideration when GAL4/UAS system is
      used to study transgene expression in early developmental stages.

PMID- 19590922
TI  - Identification of immune genes of the Agamaki clam (Sinonovacula constricta) by
      sequencing and bioinformatic analysis of ESTs.
AB  - The Agamaki clam (Sinonovacula constricta) is an economically important shellfish
      in Asia. However, genomic research on this species is still in its infancy, and
      genomic resources are largely unavailable. The objective of this study was to
      generate expressed sequence tags (ESTs) from a normalized liver complementary DNA
      library and to identify genes that function in immune defense. A total of 5,296
      ESTs were sequenced, from which 540 contigs and 3,473 singletons were identified.
      BLAST homology analysis indicated that only 20.7% of these ESTs were homologues
      of known genes while the remaining 79.3% appeared to be novel sequences. Based on
      sequence similarities, 43 putative immune genes were identified that encode
      proteases and protease inhibitors, adhesive proteins, stress proteins, lysosomal
      enzymes, and signal transduction regulators. Our study thus provides both a large
      collection of novel transcripts and a detailed annotation of immune genes for an
      important bivalve species.

PMID- 19590923
TI  - Genome size evaluation in Tetraodontiform fishes from the Neotropical region.
AB  - Smooth pufferfish of the family Tetraodontidae had become pure genomic models
      because of the remarkable compaction of their genome. This trait seems to be the
      result of DNA loss following its divergence from the sister family Diodontidae,
      which possess larger genomes. In this study, flow cytometry was used for estimate
      the genome size of four pufferfish species from the Neotropical region.
      Cytogenetic data and confocal microscopy were also used attempting to confirm
      relationships between DNA content and cytological parameters. The haploid genome
      size was 0.71 + or - 0.03 pg for Sphoeroides greeleyi, 0.34 + or - 0.01 pg for
      Sphoeroides spengleri, 0.82 + or - 0.03 pg for Sphoeroides testudineus (all
      Tetraodontidae), and 1.00 + or - 0.03 pg for Chilomycterus spinosus
      (Diodontidae). These differences are not related with ploidy level, because 46
      chromosomes are considered basal for both families. The value for S. spengleri
      represents the smallest vertebrate genome reported to date. Since erythrocyte
      cell and nuclear sizes are strongly correlated with genome size, the variation in
      this last is considered under both adaptive and evolutionary perspectives.

PMID- 19590924
TI  - Identification of a functional splice variant of 14-3-3E1 in rainbow trout.
AB  - The 14-3-3 protein family is a family of regulatory proteins involved in diverse
      cellular processes. The presence of 14-3-3 isoforms and the diversity of cellular
      processes regulated by 14-3-3 isoforms suggest functional specificity of the
      isoforms. In this study, we report the identification and characterization of a
      new isoform of the rainbow trout 14-3-3E1 gene generated by alternative splicing.
      The new isoform contains an insertion of 48 nucleotides (from intron 5) in the
      coding region of 14-3-3E1 which results in the introduction of a premature stop
      codon between exon 5 and exon 6. Thus, the alternatively spliced form of 14-3-3E1
      (14-3-3E1DeltaC17) lacks 17 amino acid residues at the C terminus encoded by the
      last exon (exon 6). Reverse-transcription polymerase chain reaction analysis
      revealed that the wild-type 14-3-3E1 (14-3-3E1wt) is ubiquitously expressed,
      while 14-3-3E1DeltaC17 shows tissue-specific as well as stage-specific expression
      during ovarian development and early embryogenesis. Analysis by yeast two-hybrid
      system demonstrated that 14-3-3E1Delta17 interacts with a number of proteins
      including ATP synthase, ankyrin repeat domain 13b, cytochrome c subunit VIa,
      cytochrome c subunit VIb, 60S ribosomal protein L34, solute carrier family 17
      member 6 (SLC17A6), troponin I, and an unknown protein. Although all of these
      proteins except for SLC17A6 also interact with 14-3-3E1wt, 14-3-3E1Delta17
      appears to have higher binding affinity with these proteins than 14-3-3E1wt.
      These findings suggest that alternative splicing affects the function and tissue
      specific expression of 14-3-3E1.

PMID- 19590925
TI  - Benthic herbivores are not deterred by brevetoxins produced by the red tide
      dinoflagellate Karenia brevis.
AB  - Gulf of Mexico blooms of the dinoflagellate Karenia brevis produce neurotoxic
      cyclic polyethers called brevetoxins. During and after a red tide bloom in
      southwestern Florida, K. brevis cells lyse and release brevetoxins, which then
      sink to the benthos and coat the surfaces of seagrasses and their epiphytes. We
      tested the possibility that these brevetoxin-laden foods alter the feeding
      behavior and fitness of a common benthic herbivore within Floridean seagrass
      beds, the amphipod Ampithoe longimana. We demonstrated that coating foods with K.
      brevis extracts that contain brevetoxins at post-bloom concentrations (1 microg
      g(-1) drymass) does not alter the feeding rates of Florida nor North Carolina
      populations of A. longimana, although a slight deterrent effect was found at
      eight and ten-fold greater concentrations. During a series of feeding choice
      assays, A. longimana tended not to be deterred by foods coated with K. brevis
      extracts nor with the purified brevetoxins PbTx-2 and PbTx-3. Florida juveniles
      isolated with either extract-coated or control foods for 10 days did not differ
      in survivorship nor growth. A similar lack of feeding response to brevetoxin
      laden foods also was exhibited by two other generalist herbivores of the
      southeastern United States, the amphipod A. valida and the urchin Arbacia
      punctulata. Given that benthic mesograzers constitute a significant portion of
      the diet for the juvenile stage of many nearshore fishes, we hypothesize that the
      ability of some mesograzers to feed on and retain brevetoxins in their bodies
      indicates that mesograzers may represent an important route of vertical
      transmission of brevetoxins through higher trophic levels within Gulf of Mexico
      estuaries.

PMID- 19590926
TI  - Cryosurgery and impaction subchondral bone graft for the treatment of giant cell
      tumor around the knee.
AB  - Giant cell tumors are neoplasms of mesenchymal stromal cells with varied
      manifestations. There is no uniform accepted treatment protocol for these tumors.
      Curettage, although an accepted method of treatment, carries a high local
      recurrence rate. Adjuvant therapies including high-speed burr debridement,
      cryotherapy, and phenol treatment have been advocated to reduce local recurrence.
      We have used these adjuvants to determine if improved cure rate with improved
      outcomes could be attained with regard to local tumor control and functional
      outcome. Twenty-eight cases of proven giant cell tumors of the distal femur and
      proximal tibia were included in this prospective case series. The lesions were at
      the upper tibia in 14 cases and the lower femur in 14 patients. The patients were
      evaluated clinically, radiologically, and by histological examination. Companacci
      grading and Enneking staging were determined. The treatment was done in the
      following steps: Curettage and further debridement with a high-speed burr,
      cryotherapy, impaction of the cavity with subchondral iliac crest bone graft,
      and, finally, cementation with or without internal fixation. Functional
      evaluation was done by Enneking's system. The follow-up time was between 24-40
      months with a mean of 34 months. The functional results of the procedure were
      rated as good to excellent with a mean of 93.9%. This technique has the
      advantages of joint preservation, excellent functional outcome, and low
      recurrence rate when compared with other treatment modalities. For these reasons,
      it is recommended as an adjuvant to curettage for most giant cell tumors of bone.

PMID- 19590927
TI  - Candidate genes associated with susceptibility for SARS-coronavirus.
AB  - Assuming that no human had any previously acquired immunoprotection against
      severe acute respiratory syndrome coronavirus (SARS-CoV) during the 2003 SARS
      outbreak, the biological bases for possible difference in individual
      susceptibility are intriguing. However, this issue has never been fully
      elucidated. Based on the premise that SARS patients belonging to a given genotype
      group having a significantly higher SARS infection rate than others would imply
      that genotype group being more susceptible, we make use of a compartmental model
      describing disease transmission dynamics and clinical and gene data of 100
      laboratory confirmed SARS patients from Chinese Han population in Taiwan to
      estimate the infection rates of distinct candidate genotype groups among these
      SARS-infected individuals. The results show that CXCL10(-938AA) is always
      protective whenever it appears, but appears rarely and only jointly with either
      Fgl2(+158T/*) or HO-1(-497A/*), while (Fgl2)(+158T/*) is associated with higher
      susceptibility unless combined with CXCL10/IP-10(-938AA), when jointly is
      associated with lower susceptibility. The novel modeling approach proposed, which
      does not require sizable case and control gene datasets, could have important
      future public health implications in swiftly identifying potential high-risk
      groups associated with being highly susceptible to a particular infectious
      disease.

PMID- 19590928
TI  - What is an unacceptable light level for direct laryngoscopy?

PMID- 19590930
TI  - The novel free radical scavenger, edaravone, increases neural stem cell number
      around the area of damage following rat traumatic brain injury.
AB  - Edaravone is a novel free radical scavenger that is clinically employed in
      patients with acute cerebral infarction, but has not previously been used to
      treat traumatic brain injury (TBI). In this study, we investigated the effect of
      edaravone administration on rat TBI. In particular, we used immunohistochemistry
      to monitor neural stem cell (NSC) proliferation around the area damaged by TBI.
      Two separate groups of rats were administered saline or edaravone (3 mg/kg) after
      TBI and then killed chronologically. We also used ex vivo techniques to isolate
      NSCs from the damaged region and observed nestin-positive cells at 1, 3, and 7
      days following TBI in both saline- and edaravone-treated groups. At 3 days
      following TBI in both groups, there were many large cells that morphologically
      resembled astrocytes. At 1 and 7 days following TBI in the saline group, there
      were a few small nestin-positive cells. However, in the edaravone group, there
      were many large nestin-positive cells at 7 days following TBI. At 3 and 7 days
      following TBI, the number of nestin-positive cells in the edaravone group
      increased significantly compared with the saline group. There were many single
      stranded DNA-, 8-hydroxy-2'-deoxyguanosine-, and 4-hydroxy-2-nonenal-positive
      cells in the saline group following TBI, but only a few such cells in the
      edaravone group following TBI. Furthermore, almost all ssDNA-positive cells in
      the saline group co-localized with Hu, nestin, and glial fibrillary acidic
      protein (GFAP) staining, but not in the edaravone group. In the ex vivo study,
      spheres could only be isolated from injured brain tissue in the saline group at 3
      days following TBI. However, in the edaravone group, spheres could be isolated
      from injured brain tissue at both 3 and 7 days following TBI. The number of
      spheres isolated from injured brain tissue in the edaravone group showed a
      significant increase compared with the saline group. The spheres isolated from
      both saline and edaravone groups were immunopositive for nestin, but not Tuj1 or
      vimentin. Moreover, the spheres differentiated into Tuj1-, GFAP-, and O4-positive
      cells after 4 days in culture without bFGF. This result indicated that the
      spheres were neurospheres composed of NSCs that could differentiate into neurons
      and glia. Edaravone administration inhibited production of free radicals known to
      induce neuronal degeneration and cell death after brain injury, and protected
      nestin-positive cells, including NSCs, with the potential to differentiate into
      neurons and glia around the area damaged by TBI.

PMID- 19590931
TI  - Appearance of epithelial and stromal genomic instability in background colorectal
      mucosa of sporadic colorectal cancer patients: relation to age and gender.
AB  - BACKGROUND: We have previously demonstrated that not only epithelial but also
      stromal genetic instability possibly contributes to colorectal tumorigenesis. To
      assess the increasing risk of carcinogenesis in the colorectum with aging, we
      examined genomic instability in both epithelia and stroma in the background
      noncancerous mucosa of patients with colorectal carcinomas. METHODS: In 213
      noncancerous colorectal mucosa samples from colorectal cancer cases and 51 normal
      mucosa specimens of diverticulosis cases, epithelial and stromal genomic
      instability was analyzed with National Cancer Institute standard microsatellite
      markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related
      markers, using a combination of laser-capture microdissection and GeneScan
      approaches. Results were compared with immunohistochemically demonstrated
      expression of FHIT, Rb, WT1, hMLH1 and hMSH2. RESULTS: Genomic instability (MSI
      and LOH) in both epithelia and stroma appeared after around 40 years of age and
      remained relatively constant thereafter at relatively low frequencies (4.8
      30.4%). The Epithelial LOH tended to show a stepwise increase in people in their
      40s and 50s along with aging, especially in males. Overall frequencies of both
      epithelial MSI and LOH in left-side colon and LOH in right-side colon were
      significantly higher in males than in females. Epithelial hMLH1 expression in MSI
      (-) cases tended to be reduced with aging. CONCLUSIONS: Genomic instability of
      both MSI and LOH in noncancerous colonic mucosa, and more particularly epithelial
      and stromal LOH, appears relatively early in adults, suggesting age-related
      changes which increase the risk of cancer development, particularly in males.

PMID- 19590929
TI  - Anthocyanins: are they beneficial in treating ethanol neurotoxicity?
AB  - Heavy alcohol exposure produces profound damage to the developing central nervous
      system (CNS) as well as the adult brain. Children with fetal alcohol spectrum
      disorders (FASD) have a variety of cognitive, behavioral, and neurological
      impairments. FASD currently represents the leading cause of mental retardation.
      Excessive alcohol consumption is associated with Wernicke-Korsakoff syndrome
      (WKS) and neurodegeneration in the adult brain. Although the cellular/molecular
      mechanism underlying ethanol's neurotoxicity has not been fully understood, it is
      generally believed that oxidative stress plays an important role. Identification
      of neuroprotective agents that can ameliorate ethanol neurotoxicity is an
      important step for developing preventive/therapeutic strategies. Targeting
      ethanol-induced oxidative stress using natural antioxidants is an attractive
      approach. Anthocyanins, a large subgroup of flavonoids present in many vegetables
      and fruits, are safe and potent antioxidants. They exhibit diverse potential
      health benefits including cardioprotection, anti-atherosclerotic activity, anti
      cancer, anti-diabetic, and anti-inflammation properties. Anthocyanins can cross
      the blood-brain barrier and distribute in the CNS. Recent studies indicate that
      anthocyanins represent novel neuroprotective agents and may be beneficial in
      ameliorating ethanol neurotoxicity. In this review, we discuss the evidence and
      potential of anthocyanins in alleviating ethanol-induced damage to the CNS.
      Furthermore, we discuss possible underlying mechanisms as well as future research
      approaches necessary to establish the therapeutic role of anthocyanins.

PMID- 19590932
TI  - Long-term beneficial effects of statins on vascular manifestations in patients
      with systemic sclerosis.
AB  - We conducted a 24-month, open-label trial to evaluate the long-term effects of
      statins on vascular symptoms in patients with systemic sclerosis (SSc). Ten
      patients received 10 mg/day atorvastatin, but two dropped out to treat other
      organ involvement. Raynaud's phenomenon, global measures of health, and
      psychological scales were assessed in addition to circulating angiogenic factors
      and endothelial activation/injury markers in eight patients at 0 (pretreatment),
      1, 3, 12, and 24 months of treatment. Circulating endothelial progenitor cells
      (EPCs) were serially quantified by cell sorting and three-color flow cytometry.
      There were no adverse events. Raynaud's phenomenon improved during atorvastatin
      treatment, with significant reductions in the Raynaud's Condition Score (P =
      0.01) and the patient assessment by visual analog scale (P = 0.0003). SSc
      associated upregulation of angiogenic factors and vascular endothelial
      activation/injury markers were reduced (P < 0.01 for all comparisons).
      Improvement in these parameters was best at 12 and 24 months of treatment. The
      EPC number was increased at 1 month of treatment (P < 0.01), but soon dropped
      below baseline. This pilot study suggests that statins may be beneficial in
      treating vascular manifestations of SSc, through their pleiotropic effects.
      However, this treatment did not correct the defect in EPC recruitment.

PMID- 19590933
TI  - Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a
      humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid
      arthritis.
AB  - The introduction of biological agents targeting tumor necrosis factor-alpha (TNF
      alpha) has brought about a paradigm shift in the treatment of rheumatoid
      arthritis (RA). Although these anti-TNF agents have excellent efficacy against
      RA, a substantial number of patients still show inadequate responses. In Western
      countries, such patients are already being treated with new classes of
      antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a
      humanized monoclonal antibody developed in Japan against the human interleukin-6
      (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but
      also seems to prevent progressive bone and joint destruction. However, there is a
      concern that TCZ might increase the risk of adverse events such as infections
      since IL-6 plays a pivotal role in the immune system. Calculating the relative
      risks of specific adverse outcomes with TCZ use remains difficult, due to
      insufficient patient numbers enrolled in clinical trials to date. This review
      presents tentative guidelines for the use of TCZ for RA patients prepared by the
      Japan College of Rheumatology and based on results of clinical trials in Japan
      and Western countries. The guidelines are intended as a guide for postmarketing
      surveillance and clinical practice, and will be revised periodically based on the
      surveillance.

PMID- 19590934
TI  - Comparison of existing disease activity indices in the follow-up of patients with
      Behcet's disease.
AB  - The objective of this study was to determine the concordance between the Iranian
      Behcet's disease dynamic activity measure (IBDDAM) or the Behcet's disease
      current activity form (BDCAF) and expert physician global assessment (PGA) in the
      evaluation of disease activity changes in Behcet's disease (BD). In a prospective
      study, 117 consecutive patients with BD were evaluated in their two consecutive
      follow-up visits by IBDDAM and BDCAF. The change in disease activity was
      determined (increased, unchanged or decreased) according to the PGA. We used
      receiver operating characteristic (ROC) curve to determine an appropriate cutoff
      point for disease activity change. Comparison was made by Stata and kappa
      analysis. Comparing the area under the ROC curve showed a significant difference
      between IBDDAM and BDCAF (p < 0.03). The difference was more significant between
      nonocular IBDDAM and BDCAF (p < 0.002). Better concordance was also observed for
      IBDDAM (nonocular and total) with PGA than BDCAF. The difference was not
      significant for ocular IBDDAM. The best cutoff point for nonocular IBDDAM was
      0.45, for ocular IBDDAM was 3.5, and for BDCAF was 1 point. IBDDAM was the
      preferred method for the evaluation of disease activity change in patients with
      BD (without ocular involvement) considering a change of at least 0.45.

PMID- 19590935
TI  - The first case of dental flossing by a Japanese macaque (Macaca fuscata):
      implications for the determinants of behavioral innovation and the constraints on
      social transmission.
AB  - We report the first case of dental flossing behavior by a Japanese macaque. We
      used cross-sectional data to assess the presence of this novel tool-use behavior
      at the group-level. Although this behavior was performed frequently by a central
      middle-ranking middle-aged female during her grooming interactions, and appeared
      at least four years ago, it remained idiosyncratic to its innovator, and until
      now has not spread to other group members. We examined the factors that may have
      favored this innovation, including the environmental context, the individual
      characteristics of the innovator, and the structural and functional aspects of
      the behavior. Group size, kinship, and dominance are socio-demographic factors
      that are likely to limit the opportunities for any group member to observe the
      innovator, and thus constrain the diffusion of this potential candidate as a new
      behavioral tradition. This is one of the rare studies to document the spontaneous
      appearance of tool-use behavior in primates under natural conditions. Identifying
      the determinants of innovations and the constraints on their diffusion within
      social groups of non-human primates is of special interest to understanding
      cultural evolution.

PMID- 19590936
TI  - Meniscal ossicle.
AB  - Meniscal ossicle, or bone within the substance of meniscus, is a rare entity and
      commonly confused with a loose body both clinically and radiologically. MRI is
      the modality that can definitely diagnose meniscal ossicle and avoid unnecessary
      diagnostic arthroscopy. Here we report one such case diagnosed using MRI; this
      patient is doing well without surgery one year after diagnosis.

PMID- 19590938
TI  - Identification of the promoter of human carbonyl reductase 3 (CBR3) and impact of
      common promoter polymorphisms on hepatic CBR3 mRNA expression.
AB  - PURPOSE: Recent studies suggest that polymorphisms in human carbonyl reductase 3
      (CBR3) influence the pharmacodynamics of doxorubicin. First, we sought to
      identify the promoter of CBR3. Next, we examined whether two CBR3 promoter
      polymorphisms (CBR3 -725T>C and CBR3 -326T>A) dictate promoter activity and
      hepatic CBR3 mRNA levels. METHODS: The promoter activities of CBR3 reporter
      constructs were investigated in HepG2 and MCF-7 cells. CBR3 mRNA levels were
      documented in 95 liver samples from white (n = 62) and black (n = 33) donors.
      Genotype-phenotype correlation analyses were used to determine the impact of the
      CBR3 -725T>C and CBR3 -326T>A polymorphisms on hepatic CBR3 mRNA levels. RESULTS:
      We identified the promoter of human CBR3. Liver samples from black donors showed
      higher relative CBR3 mRNA levels than samples from whites (CBR3 mRNA(blacks) =
      3.0 +/- 3.1 relative fold vs. CBR3 mRNA(whites) = 1.6 +/- 1.5 relative fold, p =
      0.021). The variant -725C and -326A alleles did not modify the gene reporter
      activities of engineered CBR3 promoter constructs. In line, hepatic CBR3 mRNA
      levels were not associated with CBR3 -725T>C and CBR3 -326T>A genotype status.
      CONCLUSIONS: These studies provide the first insights into the regulation and
      variable hepatic expression of polymorphic CBR3.

PMID- 19590939
TI  - Peak multiphoton excitation of mCherry using an optical parametric oscillator
      (OPO).
AB  - mCherry is a red fluorescent protein which is bright, photostable, and has a low
      molecular weight. It is an attractive choice for multiphoton fluorescence
      imaging; however, the multiphoton excitation spectrum of mCherry is not known. In
      this paper we report the two photon excitation spectrum of mCherry measured up to
      1190 nm in the near infrared (NIR) region. Skin tissues of transgenic mice that
      express mCherry were used in the experiments. mCherry in the tissues was excited
      with a Titanium:Sapphire laser and an optical parametric oscillator pumped by the
      Titanium:Sapphire laser. We found that the peak excitation of mCherry occurs at
      1160 nm.

PMID- 19590937
TI  - Matrix imbalance by inducing expression of metalloproteinase and oxidative stress
      in cochlea of hyperhomocysteinemic mice.
AB  - Clinical study reports hearing loss in patients with low folic acid (FA) and
      elevated homocysteine (Hcy). We hypothesize that elevated Hcy induces imbalance
      in matrix turnover and oxidative stress in cochlea. Cystathione beta-synthase
      heterozygous knockout mice were used as model for hyperhomocysteinemia. Matrix
      remodeling induced by Hcy resulted from elevated MMP-2, -9, and -14. MMP-2 and -9
      showed elevated gelatinase activity in CBS (+/-) cochlea. Tissue inhibitors of
      matrix metalloproteinase were significantly lower in CBS (+/-) cochlea. The
      expression analyses for MMPs and TIMPs were equally represented at protein and
      mRNA levels. Cochlea of CBS mice showed following structural changes; (1)
      detachment of tectorial membrane lying on hair cells (2) thinner s. vascularis
      (3) large fibroblast in spiral ligament. Hcy induced higher protein
      nitrotyrosination and cytosolic NADPHoxidase subunit p22(phox) in cochlea. It is
      thus suggested that Hcy induced matrix imbalance, structural changes and
      oxidative stress in cochlea.

PMID- 19590940
TI  - Two-color two-photon fluorescence laser scanning microscopy.
AB  - We present the first realization of a Two-Color Two-Photon Laser-Scanning
      Microscope (2c2pLSM) and UV fluorescence images of cells acquired with this
      technique. Fluorescence is induced by two-color two-photon absorption using the
      fundamental and the second harmonic of a Ti:Sa femtosecond laser. Simultaneous
      absorption of an 800 nm photon and a 400 nm photon energetically corresponds to
      one-photon absorption at 266 nm. This technique for Laser-Scanning Microscopy
      extends the excitation wavelength range of a Ti:Sa powered fluorescence
      microscope to the UV. In addition to the known advantages of multi-photon
      microscopy like intrinsic 3D resolution, reduced photo damage and high
      penetration depth 2c2pLSM offers the possibility of using standard high numeric
      aperture objectives for UV fluorescence imaging. The effective excitation
      wavelength of 266 nm corresponds especially well to the excitation spectrum of
      tryptophan. Hence, it is an ideal tool for label free fluorescence studies and
      imaging of intrinsic protein fluorescence which originates mainly from
      tryptophan. Thus a very sensitive natural lifetime probe can be used for
      monitoring protein reactions or changes in conformation. First measurements of
      living MIN-6 cells reveal differences between the UV fluorescence lifetimes of
      the nucleus and cytoplasm. The significance of this method was further
      demonstrated by monitoring the binding of biotin to avidin.

PMID- 19590941
TI  - Characteristics, access, utilization, satisfaction, and outcomes of healthy start
      participants in eight sites.
AB  - To describe the characteristics, access, utilization, satisfaction, and outcomes
      of Healthy Start participants in eight selected sites, a survey of Healthy Start
      participants with infants ages 6-12-months-old at time of interview was conducted
      between October 2006 and January 2007. The response rate was 66% (n = 646),
      ranging from 37% in one site to >70% in seven sites. Healthy Start participants'
      outcomes were compared to two national benchmarks. Healthy Start participants
      reported that they were satisfied with the program (>90% on five measures). Level
      of unmet need was 6% or less for most services, except for dental appointments
      (11%), housing (13%), and child care (11%). Infants had significantly better
      access to medical care than did their mothers, with higher rates of insurance
      coverage, medical homes, and checkups, and fewer unmet needs for health care.
      Healthy Start participants' rates of ever breastfeeding (72%) and putting infants
      to sleep on their backs (70%) were at or near the Healthy People 2010 objectives,
      and considerably higher than rates among low-income mothers in the ECLS. The high
      rate of health education (>90%) may have contributed to these outcomes.
      Elimination of smoking among Healthy Start participants (46%) fell short of the
      Healthy People 2010 objective (99%). The low-birth weight (LBW) rate among Black
      Healthy Start participants (14%) was three times higher than the rate for Whites
      and Hispanics (5% each). Overall, the LBW rate in the eight sites (7.5%) was
      similar to the rate for low-income mothers in the ECLS, but both rates were above
      the Healthy People 2010 objective (5%). Challenges remain in reducing disparities
      in maternal and child health outcomes. Further attention to risk factors
      associated with LBW (especially smoking) may help close the gaps. The life course
      theory suggests that improved outcomes may require longer-term investments.
      Healthy Start's emerging focus on interconception care has the potential to
      address longer-term needs of participants.

PMID- 19590942
TI  - Beyond behaviour: is social anxiety low in Williams syndrome?
AB  - Individuals with Williams syndrome (WS) exhibit striking social behaviour that
      may be indicative of abnormally low social anxiety. The present research aimed to
      determine whether social anxiety is unusually low in WS and to replicate previous
      findings of increased generalised anxiety in WS using both parent and self
      report. Fifteen individuals with WS aged 12-28 years completed the Spence
      Children's Anxiety Scale (SCAS) and the Children's Automatic Thoughts Scale
      (CATS). Their responses were compared to clinically anxious and community
      comparison groups matched on mental age. The findings suggest that WS is not
      associated with unusually low social anxiety but that generalised anxiety
      symptoms and physical threat thoughts are increased in WS, relative to typically
      developing children.

PMID- 19590943
TI  - Looking but not seeing: atypical visual scanning and recognition of faces in 2
      and 4-year-old children with autism spectrum disorder.
AB  - This study used eye-tracking to examine visual scanning and recognition of faces
      by 2- and 4-year-old children with autism spectrum disorder (ASD) (N = 44) and
      typically developing (TD) controls (N = 30). TD toddlers at both age levels
      scanned and recognized faces similarly. Toddlers with ASD looked increasingly
      away from faces with age, atypically attended to key features of faces, and were
      impaired in face recognition. Deficits in recognition were associated with
      imbalanced attention between key facial features. This study illustrates that
      face processing in ASD may be affected early and become further compromised with
      age. We propose that deficits in face processing likely impact the effectiveness
      of toddlers with ASD as social partners and thus should be targeted for
      intervention.

PMID- 19590944
TI  - Complete genome sequence of a virulent Newcastle disease virus  isolated from an
      outbreak in chickens in Egypt.
AB  - The complete genome sequence of a virulent Newcastle disease virus (NDV) isolated
      from chickens in Egypt was determined and compared to the sequence of NDV strains
      isolated from different parts of the world. The genome is 15,186 nucleotides (nt)
      long and consists of 6 genes in the order of 3'-N-P-M-F-HN-L-5'. The genome
      contains a 55-nt leader region at the 3' end and a 114-nt trailer region at the
      5' end. Interestingly, the phylogenetic analysis showed that strain Egypt is
      closely related with the NDV strains isolated in China. In addition, the sequence
      of the fusion protein cleavage site of strain Egypt was identical to that of the
      NDV strain recently isolated in Mali. Determination of complete genome sequences
      of additional NDV strains from Africa is necessary to understand the epidemiology
      of currently circulating viruses in Africa.

PMID- 19590945
TI  - Molecular characterization and pathogenicity of tomato yellow  leaf curl virus in
      China.
AB  - Several tomato production regions in China were surveyed for tomato yellow leaf
      curl disease (TYLCD), and 31 tomato leaf samples showing TYLCD-like symptoms were
      collected. The partial or full-length genomes of these isolates were sequenced
      and tomato yellow leaf curl virus (TYLCV) was detected in Shanghai, Zhejiang,
      Jiangsu Shandong and Hebei provinces of China. The TYLCV isolates found in China
      share high sequence identity ([98%) and have more than 97% sequence identity with
      TYLCVIL[ IL:Reo] (X15656). Phylogenetic relationship analysis reveals that
      although with little genetic variability, they can form two groups and all the
      TYLCV isolates in China belong to the group I. An infectious clone of TYLCV
      [CN:SH2] (AM282874) was constructed and agro-inoculated into Nicotiana
      benthamiana, N. tabacum Samsun, N. glutinosa, Solanum lycopersicum, Petunia
      hybrida, Cucumis sativus, Gossypium hirsutum, S. melongena, and Capsicum annuum.
      TYLCV-[CN:SH2] can induce severe leaf curling and stunting symptoms in these
      plants except C. sativus, G. hirsutum, S. melongena and C. annuum.We verified
      that TYLCV can trans-replicate tomato yellow leaf curl China virus DNA-b in N.
      benthamiana and S. lycopersicum and induced more severe symptoms with distortion
      and yellow vein.

PMID- 19590946
TI  - Sex therapy in a cultural context.

PMID- 19590948
TI  - Shy children are less sensitive to some cues to facial recognition.
AB  - Temperamental shyness in children is characterized by avoidance of faces and eye
      contact, beginning in infancy. We conducted two studies to determine whether
      temperamental shyness was associated with deficits in sensitivity to some cues to
      facial identity. In Study 1, 40 typically developing 10-year-old children made
      same/different judgments about pairs of faces that differed in the appearance of
      individual features, the shape of the external contour, or the spacing among
      features; their parent completed the Colorado childhood temperament inventory
      (CCTI). Children who scored higher on CCTI shyness made more errors than their
      non-shy counterparts only when discriminating faces based on the spacing of
      features. Differences in accuracy were not related to other scales of the CCTI.
      In Study 2, we showed that these differences were face-specific and cannot be
      attributed to differences in task difficulty. Findings suggest that shy children
      are less sensitive to some cues to facial recognition possibly underlying their
      inability to distinguish certain facial emotions in others, leading to a cascade
      of secondary negative effects in social behaviour.

PMID- 19590947
TI  - Brief and intensive behavioral interventions to promote sexual risk reduction
      among STD clinic patients: results from a randomized controlled trial.
AB  - The purpose of this study was to evaluate the separate and combined effectiveness
      of brief and intensive interventions for sexual risk reduction among patients at
      a sexually transmitted disease (STD) clinic. Patients (N =1483; 54% men; 64%
      African-American; M = 29.2 years old) were recruited from a publicly funded, walk
      in STD clinic. Patients completed a baseline assessment, and then were randomized
      to one of six intervention arms; each arm combined a brief intervention with an
      intensive intervention. The interventions provided different levels of
      information, motivational counseling, and behavioral skills training, guided by
      theory, formative research, and empiric precedent. Follow-up assessments,
      including STD screening, occurred at 3, 6, and 12 months post-intervention. The
      results showed that infection rates declined from 18.1% at baseline to 4.5% at 12
      months. At a 3-month follow-up, patients reported fewer sexual partners, fewer
      episodes of unprotected sex, and a lower percentage of unprotected sexual events;
      they strengthened sexual health knowledge, safer sex attitudes and intentions,
      and self-efficacy beliefs. No consistent pattern of differential risk reduction
      was observed among the six intervention conditions, nor was any evidence of decay
      from 3 to 12-month follow-ups obtained. We conclude that implementing behavioral
      interventions in a STD clinic was associated with significant reduction of sexual
      risk behavior and risk antecedents.

PMID- 19590949
TI  - Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with
      race: a meta-analysis.
AB  - MDM2 SNP309 is a single nucleotide T > G polymorphism present in intron 1 of the
      MDM2 gene. A variety of case-control studies have been published evaluating the
      association between MDM2 SNP309 and breast cancer risk. However, the published
      studies, as well as the subsequent meta-analyses, have yielded contradictory
      results. This meta-analysis aims to examine whether MDM SNP309 polymorphism may
      exert a differential effect on breast cancer risk along with race. Eligible
      articles were identified by a search of MEDLINE, Cochrane and EMBASE
      bibliographical databases for the period July 1993 to June 2009; 16 case-control
      studies were eligible (12,986 breast cancer cases, 12,993 controls). Subanalyses
      in case-control studies conducted on Chinese (3 studies, 892 cases, 1,435
      controls) and non-Chinese populations (13 studies, 12,094 cases, 11,558 controls)
      were performed. All pooled odds ratios (ORs) were derived from fixed-effects
      models given that the between-study heterogeneity was not statistically
      significant. Subanalysis on Chinese subjects demonstrated that GT and GG genotype
      were associated with increased breast cancer risk (pooled OR = 1.272, 95% CI
      1.025-1.578 and pooled OR = 1.323, 95% CI 1.034-1.694, respectively); as a result
      the overall effect of the G allele was statistically significant (pooled OR =
      1.287, 95% CI 1.048-1.579). On the contrary, no significant associations between
      MDM2 SNP309 status and breast cancer risk were demonstrated in non-Chinese
      populations. In conclusion, the association between MDM2 SNP309 and breast cancer
      is modified by race. MDM2 SNP309 represents a risk factor for breast cancer in
      Chinese women but not in non-Chinese women. This phenomenon is analogous to that
      described in the context of lung cancer.

PMID- 19590950
TI  - The proteins FABP7 and OATP2 are associated with the basal phenotype and patient
      outcome in human breast cancer.
AB  - The basal-like or basal phenotype (BP) class of breast cancers have recently
      attracted attention as a poor prognostic form of breast cancer. However, BP
      appears to encompass biologically and clinically heterogeneous tumours, resulting
      in a lack of consensus definition of BP. We analysed 48,000 gene transcripts in
      132 invasive breast carcinomas to identify two novel genes (OATP2 and FABP7)
      significantly associated with BP [defined by cytokeratin (CK)5/6 and/or CK14
      positivity]. Using a series of invasive breast carcinoma cases (n = 899),
      prepared as tissue microarrays, we assessed OATP2 and FABP7 protein expression
      using immunohistochemistry to investigate associations with clinicopathological
      variables, patients' outcome and ability to refine BP classification. A total of
      7.9 and 15.6% cases were OATP2 and FABP7 positive, respectively. OATP2 was
      associated with tumours of high histological grade (p < 0.01), ER and PgR
      negativity (p < 0.01) and shorter breast cancer-specific survival (p = 0.04).
      FABP7 expression was associated with lower lymph node stage (p < 0.01), ER and
      PgR negativity (p < 0.01). BP tumours which were FABP7 positive had a
      significantly longer BCSS (p = 0.05) and disease-free survival (p = 0.01)
      compared with FABP7 negative basal tumours (p < 0.01). OATP2 positive tumours
      were associated with adverse survival and increased risk of early recurrence.
      This study confirms the biological and clinical heterogeneity of the BP in breast
      cancer. We have identified a novel subgroup of basal tumours showing FABP7
      expression that have significantly better clinical outcome. Further studies
      analysing the role of FABP7 are therefore warranted.

PMID- 19590951
TI  - Evaluation of thermal simulation of households in the metropolitan region of Sao
      Paulo, Brazil.
AB  - This paper aims at assessing the performance of a program of thermal simulation
      (Arquitrop) in different households in the city of Sao Paulo, Brazil. The
      households were selected for the Wheezing Project which followed up children
      under 2 years old to monitor the occurrence of respiratory diseases. The results
      show that in all three study households there is a good approximation between the
      observed and the simulated indoor temperatures. It was also observed a fairly
      consistent and realistic behavior between the simulated indoor and the outdoor
      temperatures, describing the Arquitrop model as an efficient estimator and good
      representative of the thermal behavior of households in the city of Sao Paulo.
      The worst simulation is linked to the poorest type of construction. This may be
      explained by the bad quality of the construction, which the Architrop could not
      simulate adequately.

PMID- 19590952
TI  - Improved sea-urchin embryo bioassay for in situ evaluation of dredged material.
AB  - Sediments usually contain many contaminants derived from human activities. In
      case of dredging activities, these sediment-bound contaminants arise following
      the excavation and remobilization of sediments. Previous studies have used
      different species of clam, crabs, lugworms, etc. for the evaluation of dredged
      material in situ, but there are not studies that use acute bioassays for these
      purposes. The sea-urchin embryo bioassay has been chosen to characterize
      biological effects in situ in two ports of the southwest of Spain, the Port of
      Huelva and the Port of Cadiz. The sea-urchin embryo bioassay has been adapted for
      in situ evaluation of seawater quality in coastal areas, however, they are
      necessary for further improvements to take into account differences of
      temperature between sites. This temperature variation is one of the principal
      reasons (other than pollution) of larval mortality and the slow down in the
      growth rate of the urchin. In the present study a bioassay was conducted in both
      field and laboratory conditions, in order to compare the effects in situ with the
      effects under controlled conditions of temperature, salinity and oxygen
      dissolved. Results showed a good correlation between samples obtained in situ and
      in the laboratory, but in the field the percentage of normal pluteus larvae is
      less than under laboratory conditions.

PMID- 19590954
TI  - Effects of selected heavy metals (Pb, Cu, Ni, and Cd) in the aquatic medium on
      the restoration potential and accumulation in the stem cuttings of the
      terrestrial plant, Talinum triangulare Linn.
AB  - The heavy metal (Cu, Pb, Ni, and Cd) accumulation capacity of the stem cuttings
      of the terrestrial, ornamental plant, Talinum triangulare was assessed in
      hydroponic medium. The stem cuttings of T. triangulare, grew well in distilled
      water regenerating roots and aerial parts. On exposure to various concentrations
      of Cu, Pb, Ni, and Cd, a concentration dependent decrease was observed in the
      number of leaves produced and roots regenerated and an increase in the number of
      days required for the initiation of roots. The number of leaves produced showed
      an increasing trend in almost all treatment concentrations of Cu, Pb, Ni, and Cd
      with an increase in the duration of experiment, whereas, with an increase in the
      treatment concentration of metals a significant (P < 0.05) decrease was observed
      in the number of leaves produced. The number of days required for root initiation
      in metal solutions, however, increased with increasing concentration of Cu, Pb,
      Ni, and Cd. The root development was completely arrested from 10 mg l(-1) of Ni
      and 4 mg l(-1) of Cd. Compared to the control, a significant decrease was
      recorded in the number of roots produced in all treatment concentrations of Cu,
      Pb, Ni, and Cd. Pink colouration of metal solution consequent to leaching of
      plant pigment from T. triangulare was observed which was not persistent and
      disappeared after a few days. Decaying of stem was observed when exposed to Ni
      and Cd but not to Cu and Pb. Although, copper accumulation by T. triangulare at
      treatment concentration of 15 and 20 mg l(-1) exceeded 1,000 mg kg(-1) dry
      matter, necessary pot culture experiment is required before "T. triangulare" can
      be definitely classified as a Cu hyperaccumulator.

PMID- 19590953
TI  - Are uranium-contaminated soil and irrigation water a risk for human vegetables
      consumers? A study case with Solanum tuberosum L., Phaseolus vulgaris L. and
      Lactuca sativa L.
AB  - The knowledge of uranium concentration, in the products entering the human diet
      is of extreme importance because of their chemical hazard to health. Controlled
      field experiments with potatoes, beans and lettuce (Solanum tuberosum L.,
      Phaseolus vulgaris L. and Lactuca sativa L.) were carried out in a contaminated
      soil used by local farmers located near a closed Portuguese uranium mine (Cunha
      Baixa, Mangualde). The soil with high average uranium levels (64-252 mg/kg) was
      divided in two plots, and irrigated with non-contaminated and uranium
      contaminated water (<20 and >900 microg/L). Uranium maximum average concentration
      in the edible vegetables parts (mg/kg fresh weight) ranged in the following
      order: lettuce (234 microg/kg) > green bean (30 microg/kg) > potatoes without
      peel (4 microg/kg). Although uranium in soil, irrigation water and vegetables was
      high, the assessment of the health risk based on hazard quotient indicates that
      consumption of these vegetables does not represent potential adverse (no
      carcinogenic) effects for a local inhabitant during lifetime.

PMID- 19590955
TI  - Regulatory approach on environmental risk assessment. Risk management
      recommendations, reasonable and prudent alternatives.
AB  - Current knowledge shows that residues of human medicinal products at trace
      quantities are widespread in aquatic systems. The sewage treatment plants are
      pointed out as the major source discharge of these compounds on the environment.
      In this context, it has been worldwide recognised that the environmental impact
      of medicinal products have to be evaluated, according to recent EU legislation
      and regulatory guidance. The strategy of the global risk assessment includes
      primarily a pre-screening based on the estimation of exposure concentrations of
      drugs in the wastewater. The present paper addresses the decision-maker frontier
      of the ecologically relevant endpoints. Risk management recommendation and
      reasonable and prudent alternatives are discussed to minimise the possible
      environmental impact.

PMID- 19590956
TI  - Understanding the performance of different lichen species as biomonitors of
      atmospheric dioxins and furans: potential for intercalibration.
AB  - The aim of this study was to compare the performance of two lichen species-
      Xanthoria parietina and Ramalina canariensis--as biomonitors of the toxic organic
      compounds dioxins and furans (PCDD/Fs). For that purpose, the concentrations and
      profiles of PCDD/Fs found in samples of these two lichen species were compared.
      Results showed that R. canariensis presented higher concentrations than X.
      parietina and that the PCDD/F homologue profiles were substantially different
      between these species. Xanthoria parietina appeared to be a more efficient
      interceptor of more chlorinated PCDD/Fs and also of particles, whereas R.
      canariensis mainly reflected less chlorinated PCDD/Fs. Results also showed that
      the PCDD/F profile of X. parietina differed from the one found in other foliose
      and fruticose lichen species. Despite the differences observed between the
      profiles of R. canariensis and X. parietina, the calibration of PCDD/F
      concentrations between the two species was achieved, allowing the biomonitoring
      of PCDD/Fs at a regional scale using both species simultaneously.

PMID- 19590957
TI  - Dietary exposure to titanium dioxide nanoparticles in rainbow trout,
      (Oncorhynchus mykiss): no effect on growth, but subtle biochemical disturbances
      in the brain.
AB  - Our laboratory recently reported gut pathology following incidental ingestion of
      titanium dioxide nanoparticles (TiO(2) NPs) during aqueous exposures in trout,
      but there are almost no data on dietary exposure to TiO(2) NPs in fish. The aim
      of this experiment was to observe the sub-lethal effects of dietary exposure to
      TiO(2) NPs in juvenile rainbow trout (Oncorhynchus mykiss). Stock solutions of
      dispersed TiO(2) NPs were prepared by sonication without the use of solvents and
      applied to a commercial trout diet. Fish were exposed in triplicate to either,
      control (no added TiO(2)), 10, or 100 mg kg(-1) TiO(2) NPs diets for 8 weeks
      followed by a 2 week recovery period where all fish were fed the control diet.
      TiO(2) NPs had no impact on growth or nutritional performance, and no major
      disturbances were observed in red or white blood cell counts, haematocrits, whole
      blood haemoglobin, or plasma Na(+). Ti accumulation occurred in the gill, gut,
      liver, brain and spleen during dietary TiO(2) exposure. Notably, some of these
      organs, especially the brain, did not clear Ti after exposure. The brain also
      showed disturbances to Cu and Zn levels (statistically significant at weeks 4 and
      6; ANOVA or Kruskal-Wallis, P < 0.05) and a 50% inhibition of Na(+)K(+)-ATPase
      activity during TiO(2) NP exposure. Na(+)K(+)-ATPase activity was unaffected in
      the gills and intestine. Total glutathione in the gills, intestine, liver and
      brain were not affected by dietary TiO(2) NPs, but thiobarbituric acid reactive
      substances (TBARS) showed up to 50% decreases in the gill and intestine. We
      conclude that TiO(2) NPs behave like other toxic dietary metals where growth rate
      and haematology can be protected during sub-lethal exposures, but in the case of
      TiO(2) NPs this may be at the expense of critical organs such as the brain and
      the spleen.

PMID- 19590958
TI  - Mechanism of increased tyrosine (Tyr(99)) phosphorylation of calmodulin during
      hypoxia in the cerebral cortex of newborn piglets: the role of nNOS-derived
      nitric oxide.
AB  - The present study aims to investigate the mechanism of calmodulin modification
      during hypoxia and tests the hypothesis that hypoxia-induced increase in Tyr(99)
      phosphorylation of calmodulin in the cerebral cortex of newborn piglets is
      mediated by NO derived from nNOS. Fifteen piglets were divided into normoxic (Nx,
      n = 5), hypoxic (Hx, F(i)O(2) of 0.07 for 1 h, n = 5) and hypoxic-pretreated with
      nNOSi (Hx-nNOSi, n = 5) groups. nNOS inhibitor I (selectivity >2,500 vs. eNOS and
      >500 vs. iNOS) was administered (0.4 mg/kg, I.V.) 30 min prior to hypoxia.
      Cortical membranes were isolated and tyrosine phosphorylation (Tyr(99) and total)
      of calmodulin determined by Western blot using anti-phospho-(pTyr(99))-calmodulin
      and anti-pTyr antibodies. Protein bands were detected by enhanced
      chemiluminescence, analyzed by densitometry and expressed as absorbance. The
      pTyr(99) calmodulin (ODxmm(2)) was 78.55 +/- 10.76 in Nx, 165.05 +/- 12.26 in Hx
      (P < 0.05 vs. Nx) and 96.97 +/- 13.18 in Hx-nNOSi (P < 0.05 vs. Hx, P = NS vs.
      Nx). Expression of total tyrosine phosphorylated calmodulin was 69.24 +/- 13.69
      in Nx, 156.17 +/- 16.34 in Hx (P < 0.05 vs. Nx) and 74.18 +/- 3.9 in Hx-nNOSi (P
      < 0.05 vs. Hx, P = NS vs. Nx). The data show that administration of nNOS
      inhibitor prevented the hypoxia-induced increased Tyr(99) phosphorylation of
      calmodulin. Total tyrosine phosphorylation of calmodulin was similar to Tyr(99)
      phosphorylation. We conclude that the mechanism of hypoxia-induced modification
      (Tyr(99) phosphorylation) of calmodulin is mediated by NO derived from nNOS. We
      speculate that Tyr(99) phosphorylated calmodulin, as compared to non
      phosphorylated, binds with a higher affinity at the calmodulin binding site of
      nNOS leading to increased activation of nNOS and increased generation of NO.

PMID- 19590960
TI  - Absence of a dilated duct predicts benign disease in suspected pancreas cancer: a
      simple clinical rule.
AB  - BACKGROUND: Pancreatic cancer can be difficult to diagnose. Fine-needle
      aspiration (FNA) biopsies may be negative even when malignancy is present. AIMS:
      To identify endosonographic features predictive of malignancy that will separate
      patients into high- and low-risk groups, in whom a negative FNA effectively rules
      out malignancy. METHODS: Patients presenting for endoscopic ultrasound (EUS)
      evaluation for suspected pancreatic mass were prospectively enrolled. If a mass
      or abnormal lymph nodes were present, sampling via fine-needle aspiration (FNA)
      was performed. The characteristics of patients with cancer were compared to the
      characteristics of patients without cancer using Chi-square testing and t-tests.
      RESULTS: Seventy-three patients were enrolled. Thirty-three patients had cancer
      and 40 had benign disease. On multivariate analysis, only vascular or organ
      invasion and dilation of the pancreatic duct (PD) were significantly associated
      with cancer. PD dilation was examined as a stand-alone feature. The presence of a
      dilated PD placed patients into a group with a 65% prevalence of malignancy. In
      the non-dilated PD group, the prevalence of malignancy was only 17%, and in this
      group, the negative predictive value of FNA was 100%, compared to an NPV of 73%
      in the entire cohort. CONCLUSIONS: The most significant negative predictive
      endosonographic finding in patients with suspected pancreatic cancer is a non
      dilated PD. If a patient with suspected pancreatic cancer does not have a dilated
      PD and the FNA is negative for malignancy, the likelihood of cancer is low.

PMID- 19590961
TI  - Seizure detection using seizure probability estimation: comparison of features
      used to detect seizures.
AB  - This paper analyses seizure detection features and their combinations using a
      probability-based scalp EEG seizure detection framework developed by Marc Saab
      and Jean Gotman. Our method was evaluated on 525 h of data, including 88 seizures
      in 21 patients. The individual performances of the three features used by Saab
      and Gotman were compared to six alternative features, and combinations of these
      nine features were analyzed in order to find a superior detector. On a testing
      set with the combination of their three features, Saab and Gotman reported a
      sensitivity of 0.78, a false positive rate of 0.86/h, and a median detection
      delay of 9.8 s. Based on 10-fold cross-validation the testing performance of our
      implementation of their method achieved a sensitivity of 0.79, a false positive
      rate of 0.62/h, and a median detection delay of 21.3 s. A detector based on an
      alternative combination of features achieved sensitivity of 0.81, a false
      positive rate of 0.60/h, and a median detection delay of 16.9 s. By including
      filtering techniques, it was possible to achieve performance levels similar to
      Saab and Gotman using our implementation of their method, although this involved
      increases in detection delays. Of the seizure detection measures investigated,
      relative average amplitude, relative power, relative derivative, and coefficent
      of variation of amplitude provided the best performing combinations. These better
      performing features can be employed together to make robust and reliable seizure
      detectors.

PMID- 19590959
TI  - Cannabinoids and their interactions with diazepam on modulation of serum
      corticosterone concentration in male mice.
AB  - Experimental results indicate a mutual interaction between cannabinoidergic and
      GABAergic systems; however, the interaction between these systems on
      corticosterone release has not been fully investigated. In this study, we treated
      male mice with either cannabinoid compounds alone or in combination with
      diazepam. Blood samples were collected at 60 min post-injection. The serum
      corticosterone (CORT) level was measured using ELISA technique. Acute treatment
      of mice by cannabinoid receptor agonist WIN55212-2 (2.5 mg/kg; i.p.) resulted in
      a significant reduction of CORT, while treatment with either endocannabinoid
      reuptake inhibitor AM404 or endocannabinoid degradation enzyme inhibitor URB597
      increased CORT compared to control group. Co-administration of AM404 or URB597
      with cannabinoid CB1 receptor antagonist AM251 blocked the effect of these
      compounds on CORT. Treatment of mice with different doses of diazepam alone did
      not alter CORT compared to control group. However, co-administration of diazepam
      and either AM404 or WIN55212-2 significantly reduced CORT compared to the
      respective group treated with cannabinoid compound alone. Co-administration of
      ineffective dose of URB597 and ineffective dose of diazepam increased CORT level
      compared to groups treated with each compound alone. In conclusion, our findings
      suggest that the endogenous cannabinoid system is active as a modulator of CORT
      in mice and diazepam can alter the effect of cannabinoid system in the modulation
      of neuroendocrine functions.

PMID- 19590962
TI  - The priest's husband.
AB  - Clergy self-concepts provide an important resource for research into the
      psychosocial pressures that often breed domestic tension and marital discord in
      ministerial families. More than 30 years ago the Journal of Religion and Health
      published (15:3, 1976) Platt and Moss's initial study of clergy families,
      research focused on the self-perceptions of the wives of Episcopal priests. That
      investigation explored some of the intrapsychic ingredients and interpersonal
      concerns of these women. Platt and Moss [corrected] now concentrate [corrected]
      on clergy spouses from a different vantage point--the [corrected] historically
      recent phenomenon of the Episcopal priest's husband. This article grows out of
      the first formal study of such a growing parochial reality. Husbands of priests
      present novel issues because there has never been anyone like them before. They
      are men who will inevitably find themselves confronted by congregational
      expectations that can modify their self-concepts and retailer their marriages,
      "for better or for worse".

PMID- 19590963
TI  - Insulin inhibits myocardial ischemia-induced apoptosis and alleviates chronic
      adverse changes in post-ischemic cardiac structure and function.
AB  - Insulin has been shown to possess significant anti-apoptotic effect in myocardial
      ischemia/reperfusion (MI/R). However, the contribution by this protection of
      insulin to the prolonged cardiac function in rats subjected to ischemia remains
      unclear. The present study attempted to test whether early insulin treatment
      influences adverse prolonged post-ischemic cardiac structural and functional
      changes. Adult male rats were subjected to left anterior descending coronary
      artery occlusion and were randomized to receive one of the following treatments:
      saline (4 ml/kg/h i.v. injection beginning 10 min before the ischemia and
      continuing for 2 h), insulin (60 U/l, i.v. injection following the same routine,
      and hypodermic injection of insulin (0.5 U/ml, 1 ml/kg/d) for 3 days after the
      ischemia surgery) or insulin plus wortmannin (15 mug/kg i.v. injection 15 min
      before each insulin administration). Treatment with insulin significantly reduced
      infarct size, decreased plasma creatine kinase and lactate dehydrogenase
      activities, decreased apoptosis index and caspase-3 activity (all P < 0.01 vs.
      saline), and improved cardiac function 24 h after ischemia. Importantly, at the
      end of 4 weeks after the ischemia surgery, MI rats receiving insulin treatment
      showed smaller left ventricle (LV) cavity and thicker systolic interventricular
      septum, and increased cardiac ejection fraction and LV fractional shortening (all
      P < 0.05 vs. saline). Inhibition of insulin signaling with wortmannin not only
      blocked insulin's anti-apoptotic effect, but also almost completely abolished
      effects of insulin on cardiac structure and function. These data indicate that
      inhibition of apoptosis by early insulin treatment alleviates chronic adverse
      changes in post-ischemic cardiac structure and function.

PMID- 19590966
TI  - High genetic differentiation between an African and a non-African strain of
      Drosophila simulans revealed by segregation distortion and reduced crossover
      frequency.
AB  - Drosophila simulans strains originating from Madagascar and nearby islands in the
      Indian Ocean often differ from those elsewhere in the number of sex comb teeth
      and the degree of morphological anomaly in hybrids with D. melanogaster. Here, we
      report a strong segregation distortion in the F1 intercross between two D.
      simulans strains originating from Madagascar and the US, possibly at both the
      gametic and zygotic levels. Strong bias against alleles of the Madagascar strain
      was observed for all ten marker loci distributed over the entire second
      chromosome in the F1 intercross, but only a few showed a weak distortion in the
      isogenic backgrounds of either strains. Significant deviations of genotype
      frequencies from Hardy-Weinberg proportions were consistently observed for the
      second chromosome. By contrast, the X and third chromosomes did not show any
      strong segregation distortion. Crossover frequency on the second chromosome was
      uniformly reduced in isogenic backgrounds whereas the map lengths in the F1
      intercross were comparable to or larger than that of the standard D. melanogaster
      map. We discuss these findings in relation to previous studies on other traits
      and interspecific differences between D. mauritiana, which is endemic to
      Mauritius Island, and D. simulans.

PMID- 19590967
TI  - Degradation of pyrene by an enteric bacterium, Leclercia adecarboxylata PS4040.
AB  - A newly discovered enteric bacterium Leclercia adecarboxylata PS4040, isolated
      from oily sludge contaminated soil sample was reported for degradation of
      polycyclic aromatic hydrocarbons (Appl Environ Microbiol 70:3163-3166, 2004a).
      This strain could degrade 61.5% of pyrene within 20 days when used as sole source
      of carbon and energy. The time course degradation experiment detected several
      intermediate products and the metabolites were identified by gas chromatography
      mass spectrometry analysis. Metabolite I was the detected on the 5th day and was
      identified as 1-hydroxypyrene and was detected till 10th day. Metabolite II which
      was detected on 10th day was identified as 1,2-phenanthrenedicarboxylic acid.
      Metabolite III and Metabolite IV were identified as 2-carboxy benzaldehyde and
      ortho-phthalic acid, respectively and were detected in the culture broth on 10th
      and 15th day. 1,2-benzene diol (catechol) was the fifth metabolite detected in
      the culture extracts on the 15th day and was subsequently reduced on day 20.
      Identification of Metabolite I as 1-hydroxypyrene was further investigated as
      this intermediate was not previously reported as a ring oxidation product for
      degradation of pyrene by bacterial strains. Purification by preparative high
      performance liquid chromatography and nuclear magnetic resonance spectroscopy,
      confirmed the identification of Metabolite I as 1-hydroxypyrene. L.
      adecarboxylata PS4040 could also use 1-hydroxypyrene as a sole source of carbon
      and energy. Thus a probable pathway for degradation of pyrene by enteric
      bacterium is proposed in this study, with 1-hydroxypyrene as initial ring
      oxidation product.

PMID- 19590965
TI  - Insights into the substrate specificity, inhibitors, regulation, and
      polymorphisms and the clinical impact of human cytochrome P450 1A2.
AB  - Human CYP1A2 is one of the major CYPs in human liver and metabolizes a variety of
      clinically important drugs (e.g., clozapine, tacrine, tizanidine, and
      theophylline), a number of procarcinogens (e.g. benzo[a]pyrene and aflatoxin
      B(1)), and several important endogenous compounds (e.g. steroids and arachidonic
      acids). Like many of other CYPs, CYP1A2 is subject to induction and inhibition by
      a number of compounds, which may provide an explanation for some drug
      interactions observed in clinical practice. A large interindividual variability
      in the expression and activity of CYP1A2 and elimination of drugs that are mainly
      metabolized by CYP1A2 has been observed, which is largely caused by genetic
      (e.g., SNPs) and epigenetic (e.g., DNA methylation) and environmental factors
      (e.g., smoking and comedication). CYP1A2 is primarily regulated by the aromatic
      hydrocarbon receptor (AhR) and CYP1A2 is induced through AhR-mediated
      transactivation following ligand binding and nuclear translocation. To date, more
      than 15 variant alleles and a series of subvariants of the CYP1A2 gene have been
      identified and some of they have been associated with altered drug clearance and
      response to drug therapy. For example, lack of response to clozapine therapy due
      to low plasma drug levels has been reported in smokers harboring the -163A/A
      genotype; there is an association between CYP1A2*1F (-163C>A) allele and the risk
      for leflunomide-induced host toxicity. The *1F allele is associated with
      increased enzyme inducibility whereas *1C causes reduced inducibility. Further
      studies are warranted to explore the clinical and toxicological significance of
      altered CYP1A2 expression and activity caused by genetic, epigenetic, and
      environmental factors.

PMID- 19590969
TI  - Heavy metals in brick kiln located area using atomic absorption
      spectrophotometer: a case study from the city of Peshawar, Pakistan.
AB  - Environmental pollution is one of the burning issues of the world. In developed
      countries, there are lot of awareness about the environment and the impact of
      various industries on their life and surroundings. A little has been done in this
      direction in developing countries. In Pakistan, a big problem is the rapid
      conglomeration of the brick kilns in the outskirts of nearly all the urban
      centers to cope with the rapid construction work in big cities. A huge amount of
      low-grade coal or rubber tires is used as fuel in a very non-scientific manner.
      The purpose of the present study was to look into the impact of the brick kilns
      on the different aspects of environmental pollution caused by these kilns.
      Concentration of metals Cu, Co, Zn, Pb, Cr, Ni, Cd, and Mn were measured on 36
      soil samples collected from the area and the same number of plant samples in
      order to establish the distribution of heavy metals in the area and to determine
      the effect of this distribution on the surrounding atmosphere and the possible
      effects on human life.

PMID- 19590970
TI  - A knowledge-based method to predict the cooperative relationship between
      transcription factors.
AB  - Identifying the cooperation between transcription factors is crucial and
      challenging to uncover the mystery behind the complex gene expression patterns.
      Computational methods aimed to infer transcription factor cooperation are
      expected to get good results if we can integrate the knowledge (existed
      functional/structural annotations) of proteins. In this contribution, we proposed
      an information integrative computational framework to infer the cooperation
      between transcription factors, which relies on the hybridization-space method
      that can integrate the annotation information of proteins. In our computational
      experiments, by using function domain annotations only, on our testing dataset,
      the overall prediction accuracy and the specificity reaches 84.3% and 76.9%,
      respectively, which is a fairly good result and outperforms the prediction by
      both amino acid composition-based method and BLAST-based approach. The
      corresponding online service TFIPS (Transcription Factor Interaction Prediction
      System) is available on http://pcal.biosino.org/cgi-bin/TFIPS/TFIPS.pl.

PMID- 19590968
TI  - Enhanced expression and shedding of receptor activator of NF-kappaB ligand during
      tumor-bone interaction potentiates mammary tumor-induced osteolysis.
AB  - The bone microenvironment plays a critical role in tumor-induced osteolysis and
      osteolytic metastasis through tumor-bone (TB)-interaction. Receptor activator of
      nuclear factor-kappaB (RANK) ligand (RANKL) is one of the critical signaling
      molecules involved in osteolysis and bone metastasis. However, the regulation and
      functional significance of RANKL at the TB-interface in tumor-induced osteolysis
      remains unclear. In this report, we examined the role of tumor-stromal
      interaction in the regulation of RANKL expression and its functional significance
      in tumor-induced osteolysis. Using a novel mammary tumor model, we identified
      that RANKL expression was upregulated at the TB-interface as compared to the
      tumor alone area. We demonstrate increased generation of sRANKL at the TB
      interface, which is associated with tumor-induced osteolysis. The ratio of RANKL
      to osteoprotegrin (OPG), a decoy receptor for RANKL, at the TB-interface was also
      increased. Targeting RANKL expression with antisense oligonucleotides (RANKL
      ASO), significantly abrogated tumor-induced osteolysis, decreased RANKL
      expression and the RANKL:OPG ratio at the TB-interface. Together, these results
      demonstrate that upregulation of RANKL expression and sRANKL generation at the TB
      interface potentiates tumor-induced osteolysis.

PMID- 19590964
TI  - Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?
AB  - Cancer is a hyperproliferative disorder that is usually treated by
      chemotherapeutic agents that are toxic not only to tumor cells but also to normal
      cells, so these agents produce major side effects. In addition, these agents are
      highly expensive and thus not affordable for most. Moreover, such agents cannot
      be used for cancer prevention. Traditional medicines are generally free of the
      deleterious side effects and usually inexpensive. Curcumin, a component of
      turmeric (Curcuma longa), is one such agent that is safe, affordable, and
      efficacious. How curcumin kills tumor cells is the focus of this review. We show
      that curcumin modulates growth of tumor cells through regulation of multiple cell
      signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell
      survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway
      (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway
      (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and
      AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also
      described in detail.

PMID- 19590971
TI  - Shelf life of different fish species stored with passive refrigeration (PRS).

PMID- 19590972
TI  - Phylogenetic analysis of Mycoplasma suis isolates based on 16S rRNA gene sequence
      in China.
AB  - To perform phylogenetic analysis of Mycoplasma suis isolates derived from China
      to define the nature of this pathogen, nearly complete of 16S rRNA genes from
      Chongqing, Sichuan, Henan and Guangdong isolates were amplified by PCR and
      sequenced. The four sequences from the blood samples in this study, with other 17
      Hemoplasmas sequences and related 3 mycoplasma sequences available in the
      GenBank, were aligned using Clustal X (version 1.83) sequences alignment program.
      Maximum parsimony, neighbor-joining and minimum evolution (MEGA 4.0) algorithms
      were used to create phylogenetic trees. Phylogenetic analysis of these sequences
      showed that all hemoplasma species were located within a single clade and were
      most closely related to M. pneumoniae group. The hemoplasma species were further
      subdivided into two distinct groups, one containing M.wenyonii, M.suis and
      Candidatus M. haemominutum and the other containing M. haemofelis and M.
      haemocanis. Within the former clade, four M.suis isolates from Mainland China and
      other M.suis species formed a monophyletic group in the tree. A tendency of clear
      geographical grouping of the isolate was evident.

PMID- 19590973
TI  - The clearance of unidentified uremic solutes (with molecular weight under 5 kDa)
      plays an important role in hemodialyzer selection.
AB  - BACKGROUND: The purpose of this study was to evaluate two commercial
      hemodialyzers (F100 and P21) through the clearance of identified and unidentified
      uremic solutes. METHODS: We investigated plasma samples from healthy and uremic
      subjects. RESULTS: We found three unidentified uremic solutes (P1, P2, and P3)
      after HPLC analysis of plasma samples. Then, we determined the clearance of four
      identified and the three unidentified uremic solutes in patients with F100 and
      P21. There was no significance between F100 and P21 in clearance of four
      identified uremic solutes. By contrast, the clearance of P1 and P2 with F100 was
      superior with the P21 (P < 0.05). CONCLUSION: Our data suggest that selection of
      a hemodialyzer based on the clearance of identified uremic solutes might not be
      sufficient. Application of external techniques to determine additional external
      factors (i.e., clearance of unidentified uremic solutes) can facilitate a better
      decision in the selection of the ideal hemodialyzer.

PMID- 19590974
TI  - Patient awareness of smoking as a risk factor for bladder cancer.
AB  - INTRODUCTION: Data on general population's and bladder cancer patients'
      perception of smoking as a risk factor for bladder cancer are limited. To
      determine urological patients' awareness of smoking as a risk factor for bladder
      cancer. METHODS: This prospective observational study included 202 consecutive
      urological inpatients, using a structured questionnaire. We evaluated urological
      patients' awareness of smoking as a risk factor for bladder cancer and other
      smoking-related pathologies. Smoker-bladder cancer patients were asked whether
      they believed that smoking was related to their present bladder problem, whether
      their treating urologist had ever advised them on the same, and whether they
      intended to quit. RESULTS: Only 118 of 202 patients (58.4%) stated that they were
      aware of smoking as a risk factor for bladder cancer, as apposed to 94.6% for
      chronic obstructive pulmonary disease, 91.6% for heart and vascular problems, and
      92.1%, for lung cancer. Perception was unrelated to age, gender, smoking habits,
      or history of heart or chronic lung disease. Of current smokers/TCC patients,
      56.4% believed that smoking is related to their problem and 61.5% intended to
      quit. The majority (84.6%) had been already warned by their attending physicians.
      CONCLUSIONS: Urological patients' awareness of smoking as a risk factor for
      bladder cancer is lower than that for other smoking-related entities. The role of
      the urologist should not be restricted only to diagnosis and treatment, but
      should also include counseling patients on the need for radical changes of their
      life style.

PMID- 19590975
TI  - The effect of varicocele on seminal plasma and serum inhibin-B levels in
      adolescent and adult men.
AB  - INTRODUCTION: In the present study, the relationship between serum/seminal plasma
      and serum FSH and seminal parameters was evaluated in adults and adolescent
      varicocele patients and compared with normal fertile cases. METHODS: A total of
      50 adult patients with varicocele (Group-1) and 50 adolescents with varicocele
      (Group-2) were enrolled into the study. Fifty fertile cases without any scrotal
      pathology were accepted as control group (Group-3). Serum gonadotropin, sex
      steroids and serum and seminal plasma inhibin-B levels were measured, and semen
      analysis was performed after 2 and 5 days of sexual abstinence. All parameters
      were compared among three groups by using one-way ANOVA test. RESULTS: There were
      statistically significant differences among three groups on seminal parameters
      due to disturbed spermatogenesis in patients with varicocele (P < 0.05). However,
      there were not statistical differences between serum and seminal plasma Inhibin-B
      levels among groups. In varicocele patients, serum inhibin-B levels showed
      negative and significant correlation only with FSH levels (r = -0.253, P =
      0.011). On the contrary, neither serum nor seminal plasma inhibin-B levels showed
      significant correlation with seminal parameters. CONCLUSION: While varicocele
      affects different mechanisms in the regulation of spermatogenesis in testes,
      serum and seminal plasma inhibin-B have not any role in decreased spermatogenesis
      in varicocele.

PMID- 19590976
TI  - Photon echo studies of photosynthetic light harvesting.
AB  - The broad linewidths in absorption spectra of photosynthetic complexes obscure
      information related to their structure and function. Photon echo techniques
      represent a powerful class of time-resolved electronic spectroscopy that allow
      researchers to probe the interactions normally hidden under broad linewidths with
      sufficient time resolution to follow the fastest energy transfer events in light
      harvesting. Here, we outline the technical approach and applications of two types
      of photon echo experiments: the photon echo peak shift and two-dimensional (2D)
      Fourier transform photon echo spectroscopy. We review several extensions of these
      techniques to photosynthetic complexes. Photon echo peak shift spectroscopy can
      be used to determine the strength of coupling between a pigment and its
      surrounding environment including neighboring pigments and to quantify timescales
      of energy transfer. Two-dimensional spectroscopy yields a frequency-resolved map
      of absorption and emission processes, allowing coupling interactions and energy
      transfer pathways to be viewed directly. Furthermore, 2D spectroscopy reveals
      structural information such as the relative orientations of coupled transitions.
      Both classes of experiments can be used to probe the quantum mechanical nature of
      photosynthetic light-harvesting: peak shift experiments allow quantification of
      correlated energetic fluctuations between pigments, while 2D techniques measure
      quantum beating directly, both of which indicate the extent of quantum coherence
      over multiple pigment sites in the protein complex. The mechanistic and
      structural information obtained by these techniques reveals valuable insights
      into the design principles of photosynthetic light-harvesting complexes, and a
      multitude of variations on the methods outlined here.

PMID- 19590977
TI  - Using human sera to identify a 52-kDa exoantigen of Penicillium chrysogenum and
      implications of polyphasic taxonomy of anamorphic ascomycetes in the study of
      antigenic proteins.
AB  - We are interested in isolating and identifying antigenic fungal proteins from
      species that grow on damp building materials. The indoor clade of Penicillium
      chrysogenum, the so-called Fleming clade, is the most common species of
      Penicillium on moldy building materials. We have identified a 52-kDa marker
      protein for the indoor clade of P. chrysogenum not present in a taxonomically
      diverse selection of fungi. It is found in high concentrations in protein
      extracted from the fungus grown on paper-faced gypsum wallboard. During this
      process, we illuminated the variability in response to patient sera and of
      strains of the fungus collected over a wide geographic area. From a collection of
      sera from all over the USA, 25 of the 48 patients reacted to the 52-kDa protein
      from this prescreened collection of sera. Most strain/antibody combinations had
      proportionate ELISA response associated with the presence of the target. However,
      approximately 25% of the strain/patient serum combinations included people who
      responded to many common allergens from the Penicillia. All the P. chrysogenum
      strains tested produced the target protein. However, there was considerable
      variability in patient IgG response to 32-, 30-, and 18-kDa antigens and in their
      production by the various clade 4 strains. The target protein was not found in
      spores or culture extracts of a wide selection of relevant fungi. It appears that
      the previous studies have been conducted on strains of the fungus from the three
      clades not those associated with the built environment.

PMID- 19590978
TI  - A novel polymorphism of GDF5 gene and its association with body measurement
      traits in Bos taurus and Bos indicus breeds.
AB  - Body measurement traits, influenced by genes and environmental factors, play
      numerous important roles in the value assessment of productivity and economy.
      Growth differentiate factor 5 (GDF5), involved in the development and maintenance
      of bone and cartilage, is an important candidate gene for body measurement traits
      selection through marker-assisted selection (MAS). In this study, based on the
      PCR-RFLP technology, we discovered and evaluated the potential association of the
      single nucleotide polymorphism (SNP) (T586C in exon 1) of the bovine GDF5 gene
      with body measurement traits in 985 Bos taurus breed, 42 Bos indicus breed and 76
      Bos indicus x Bos taurus individuals. As the SNP marker, there were the
      significant effects on the Body length (BL) in the Bos taurus (BT) and Bos
      indicus x Bos taurus (BMY) populations (P < 0.05). In BT population, animals with
      the genotype TT had lower mean values for BL and Hip width (HW) than these with
      the TC and CC genotype (P < 0.01). In BMY population, animals with the genotype
      TC had lower mean values for BL than these with the genotype CC (P < 0.05). These
      results suggest that the SNP of the GDF5 gene could be a very useful genetic
      marker for body measurement traits in the bovine reproduction and breeding.

PMID- 19590979
TI  - Readability estimates for commonly used health-related quality of life surveys.
AB  - PURPOSE: To estimate readability of seven commonly used health-related quality of
      life instruments: SF-36, HUI, EQ-5D, QWB-SA, HALex, Minnesota Living with Heart
      Failure Questionnaire (MLHFQ), and the NEI-VFQ-25. METHODS: The Flesch-Kincaid (F
      K) and Flesch Reading Ease (FRE) formulae were used to estimate readability for
      every item in each measure. RESULTS: The percentage of items that require more
      than 5 years of formal schooling according to F-K was 50 for the EQ-5D, 53 for
      the SF-36, 80 for the VFQ-25, 85 for the QWB-SA, 100 for the HUI, HALex, and the
      MLHFQ. The percentage of items deemed harder than "easy" according to FRE was 50
      for the SF-36, 67 for the EQ-5D, 79 for the QWB-SA, 80 for the VFQ-25, 100 for
      the HUI, HALex, and the MLHFQ. CONCLUSIONS: All seven surveys have a substantial
      number of items with high readability levels that may not be appropriate for the
      general population.

PMID- 19590980
TI  - Melatonin and tryptophan counteract lipid peroxidation and modulate superoxide
      dismutase activity in ringdove heterophils in vivo. Effect of antigen-induced
      activation and age.
AB  - Aging is associated with an increased production of free radicals and alterations
      in the mechanisms of adaptation to stress. A number of studies have shown a
      causal connection between age-related oxidant/antioxidant imbalance and the
      diminution of an organism's melatonin levels in old age. Restoration of this
      rhythm may contribute to the re-stabilization of cellular homeostasis. The
      present work was aimed at examining the effect of the administration of melatonin
      or its precursor, the amino acid tryptophan, on heterophil lipid peroxidation
      (LPO) levels and superoxide dismutase (SOD) activity in heterophils from young (4
      5 year) and old (12-14 year) ringdoves (Streptopelia risoria) under both basal
      and antigen-induced (stressful) conditions. Young animals were treated for 3
      consecutive days with a single daily oral dose (0.25 mg) of melatonin at 1900
      hours while old animals were treated for 3 consecutive days with either an oral
      dose (2.5 mg) of melatonin at 1900 hours or an oral capsule of 300 mg/kg body
      weight of L-tryptophan at 0900 hours. Non-treated old animals presented lower
      circulating levels of melatonin at night and higher levels of malonaldehyde (MDA)
      both day and night when compared to young birds. In both age groups, LPO levels
      were lower at night than during the day. Melatonin or tryptophan treatments
      significantly increased serum melatonin levels, reinforced SOD activity, and
      reduced MDA levels induced by the antigen. Melatonin and tryptophan may be useful
      agents for the treatment of disease states and processes in which an excessive
      production of oxidative damage occurs.

PMID- 19590982
TI  - Smarter regulations: commentary on "Responsible conduct by life scientists in an
      age of terrorism".
AB  - In the United States a rapidly increasing regulatory burden for life scientists
      has led to questions of whether the increased burden resulting from the Select
      Agent Program has had adverse effects on scientific advances. Attention has
      focussed on the regulatory "fit" of the Program and ways in which its design
      could be improved. An international framework convention to address common
      concerns about biosecurity and biosafety is a logical next step.

PMID- 19590983
TI  - Nasal-type NK/T-cell lymphoma with palatal ulcer as the earliest clinical
      manifestation: a case report with literature review.
AB  - Extranodal nasal natural killer (NK)/T-cell lymphoma is a very rare kind of
      lymphoma, Oral cavity involvement of extranodal natural killer/T-cell lymphoma,
      nasal type is extremely rare, and its clinicopathologic features are also poorly
      understood. Recently, we experienced an unusual case of Epstein-Barr virus
      associated, extranodal NK/T-cell type with a unhealed palatal ulcer as the
      earliest clinical feature. It is a challenge for oral medicine specialists to
      make the early diagnosis for this special type of tumor.

PMID- 19590981
TI  - Revealing system-level correlations between aging and calorie restriction using a
      mouse transcriptome.
AB  - Although systems biology is a perfect framework for investigating system-level
      declines during aging, only a few reports have focused on a comprehensive
      understanding of system-level changes in the context of aging systems. The
      present study aimed to understand the most sensitive biological systems affected
      during aging and to reveal the systems underlying the crosstalk between aging and
      the ability of calorie restriction (CR) to effectively slow-down aging. We
      collected and analyzed 478 aging- and 586 CR-related mouse genes. For the given
      genes, the biological systems that are significantly related to aging and CR were
      examined according to three aspects. First, a global characterization by Gene
      Ontology (GO) was performed, where we found that the transcriptome (a set of
      genes) for both aging and CR were strongly related in the immune response, lipid
      metabolism, and cell adhesion functions. Second, the transcriptional modularity
      found in aging and CR was evaluated by identifying possible functional modules,
      sets of genes that show consistent expression patterns. Our analyses using the
      given functional modules, revealed systemic interactions among various biological
      processes, as exemplified by the negative relation shown between lipid metabolism
      and the immune response at the system level. Third, transcriptional regulatory
      systems were predicted for both the aging and CR transcriptomes. Here, we suggest
      a systems biology framework to further understand the most important systems as
      they age.

PMID- 19590984
TI  - Cloning and heterologous expression of a novel endoglucanase gene egVIII from
      Trichoderma viride in Saccharomyces cerevisiae.
AB  - Endoglucanase is a major cellulolytic enzyme produced by the fungus Trichoderma
      viride. The 1,317 bp cDNA of endoglucanase gene egVIII was cloned from T. viride
      AS3.3711, encoding a 438 amino acid protein with a calculated molecular mass of
      46.86 kDa and isoelectric point of 4.32. Sequence analysis suggested that EGVIII
      belonged to the glycosyl hydrolase family 5. The N-terminal region of EGVIII
      contains a signal peptide sequence of 19 amino acid residues, indicating that it
      is an extracellular enzyme. Transcription of the egVIII gene in T. viride
      AS3.3711 can be induced by carboxymethyl cellulose sodium (CMC-Na), sucrose,
      microcrystalline cellulose, and corn stalk, and inhibited by glucose and
      fructose. The alpha-mating factor signal can effectively enhance the secretion of
      the recombinant EGVIII in Saccharomyces cerevisiae, as demonstrated by the
      enzymatic activity of recombinant yeast IpYEMalpha-xegVIII in the supernatant,
      which was 0.86 times higher than that of the IpYES2-egVIII. Recombinant
      endoglucanase EGVIII showed optimal activity at a temperature of 60 degrees C and
      pH of 6.0. It was stable when incubated from 35 degrees C to 70 degrees C for 1
      h. The enzymatic activity of recombinant EGVIII was stable at a pH 3.0 to 7.5 at
      50 degrees C and reached the highest level at 0.174U when activated by 75 mM of
      Zn(2+). The Michaelis-Menten constant (Km) and Kcat values for CMC-Na and
      cellotriose hydrolysis were 3.82 mg/ml, 9.56 s(-1) and 1.75 mg/ml, 7.08 s(-1),
      respectively. Transgenic yeast strain IpYEMalpha-xegVIII might be useful for
      renewable fuels industries.

PMID- 19590985
TI  - Utilization of salmon milt DNA against UV damage.
AB  - We examined the effect of ultraviolet (UV) irradiation on the UV spectra and
      radical scavenging activity of DNA strands and found that the absorption spectra
      of salmon milt DNA was extended up to about 350 nm after ultraviolet C (UVC, 100
      280 nm) irradiation with 300 kJ/m(2). The UV B (UVB, 280-315 nm) protection
      ability of UVC-irradiated salmon milt DNA for a single-stranded target DNA (19
      mer) was further studied. The percentage of damaged target DNA after 50 kJ/m(2)
      of UVB irradiation in the presence of UVC-irradiated salmon milt DNA, UVC
      unirradiated salmon milt DNA, and 2-phenylbenzimidazole sulfonic acid was
      estimated to be 24.6%, 27.0%, and 18.9%, respectively. Moreover, the ultraviolet
      A (UVA, 315-400 nm)/UVB ratio and critical wavelength of natural (UVC
      unirradiated) salmon milt DNA were estimated to be 0.13 and 313 nm, respectively,
      whereas those of the UVC-irradiated salmon milt DNA were 0.34 and 375 nm,
      respectively. Interestingly, the value of 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging activity in UVC-irradiated salmon milt DNA was about five times higher
      than that of UVC-unirradiated salmon milt DNA. These results indicate that the
      UVC-irradiated salmon milt DNA could be useful as a protector against a wide
      range of UV light from UVC approximately UVA.

PMID- 19590987
TI  - Present status and perspectives of stem cell-based therapies for gastrointestinal
      diseases.
AB  - In recent years the interest in stem cell-based therapies for gastrointestinal
      injury has been increasing continuously. From the clinical point of view,
      transplantation of bone marrow derived stem cells may represent an alternative
      therapy for gastrointestinal injury, such as radioactive injury, inflammatory
      bowel disease, and other refractory gastrointestinal tract injury. There were
      several reports indicated that bone marrow derived stem cells located in the
      injured gastrointestinal tract and contributed to its regeneration by
      differentiating into functional epithelia cells or infusing with the
      gastrointestinal stem cells. Although the concept of cell-based therapy for
      various diseases of the gastrointestinal is widely accepted, the practical
      approach in humans remains difficult. Here we discussed the recent published data
      on clinical and experimental bone marrow stem cell transplantation and the
      possible role of stem cells in gastrointestinal tissue repair.

PMID- 19590989
TI  - Retraction. Therapeutic window of stem cell potential for targeting pediatric
      malignant brain tumors: an opportunity for stem cell therapy.

PMID- 19590988
TI  - Isolation of mesenchymal stem cells from human placental decidua basalis and
      resistance to hypoxia and serum deprivation.
AB  - Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy
      and tissue engineering, which can be isolated from various sources of human adult
      tissues such as bone marrow and adipose tissue. However, cells from these tissues
      must be obtained through invasive procedures and sometimes the individual
      difference is hard to control. Hence, the search continues for an ethically
      conducive, easily accessible and controllable source of stem cells. We herein
      report the isolation of a population of stem cells from the human placental
      decidua basalis (termed as PDB-MSCs), a maternal portion of placenta. PDB-MSCs
      were further shown to express markers common to MSCs and positive for SSEA-1,
      SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and Oct-4. In order to facilitate the further
      utility in ischemic diseases, we tested the apoptosis of PDB-MSCs in hypoxia and
      serum deprivation, two components of ischemia in vivo. Taken together, our
      findings indicate that PDB-MSCs are resistant to hypoxia and serum deprivation,
      which may relate to Bcl-2.

PMID- 19590991
TI  - Discriminating semantic from episodic relatedness in young and older adults.
AB  - The ability of young (aged 18-30) and older (aged 60-80) adults to discriminate
      pre-experimental (semantic) from experimental (episodic) associations was
      examined. Participants studied a list containing semantically related and
      unrelated word pairs and then made either associative recognition (Experiments 1a
      and b) or semantic relatedness (Experiment 2) judgments at various response
      deadlines. For associative recognition judgments, both young and older adults
      benefited from semantic relatedness, leading to more hits for related than
      unrelated pairs, and at the long response deadline, older adults' performance on
      those pairs matched that of young participants. Also, both young and older adults
      demonstrated superior discrimination for unrelated lures whose members had
      originally been studied in related pairs - evidence for recall-to-reject
      processing in both age groups. In making semantic relatedness judgments, both
      young and older adults showed an episodic priming effect. When older adults can
      rely on long-standing associations, their performance resembles that of young
      adults - both in associative recognition and in episodic priming.

PMID- 19590992
TI  - Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a
      patient with IgM-associated AL amyloidosis.
AB  - A male patient with primary AL amyloidosis who had been suffering from systemic
      lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and
      high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab
      followed by autologous peripheral blood stem cell transplantation. Four years
      after complete hematological remission he showed marked reduction in size of the
      amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if
      the chemotherapy succeeds in persistent inhibition of the production of
      amyloidogenic immunoglobulin light chains.

PMID- 19590990
TI  - Characteristics and quality of life analysis of caregivers of cancer patients.
AB  - Cancer affects not only the individuals with cancer, but also their families
      considerably. The aim of this study was to determine the sociodemographic
      characteristics and home care needs of caregivers of cancer patients receiving
      chemotherapy and evaluate their quality of life scores. A total of 126 primary
      caregivers of patients receiving chemotherapy who were eligible for inclusion
      criteria participated in the study. Data were collected using a questionnaire
      that included sociodemographic questions for both patients and caregivers and the
      World Health Organization Quality of Life-Short Form, Turkish Version (WHOQOL
      BREF(TR)) for the caregivers. The mean domain scores of WHOQOL-BREF(TR) were 15.3
      +/- 2.8 for physical, 14.6 +/- 2.8 for psychological, 14.4 +/- 3.3 for social,
      13.7 +/- 2.8 for environment, and 14 +/- 2.5 for national environment domains.
      Caregivers were, on average, younger than the patients and the mean age of the
      caregivers was 45 years. Around 70% of caregivers were living with the patients,
      60.3% of caregivers shared the care-giving process with someone else, and his/her
      children supported in care-giving activities in 20.6%. According to caregivers,
      patients needed assistance for one or more daily living activities. Caregivers'
      higher age, unemployment status, female gender, low education level, their own
      diagnosed health problems, care duration above 18 months, and having difficulties
      to continue social activities had negative effects on their quality of life.
      Cancer patients' families are also affected from cancer. We may suggest that
      including caregivers in the context of home care and universalizing home care
      programs can reduce caregivers' burden.

PMID- 19590993
TI  - Rituximab therapy in nephrotic syndrome due to AH amyloidosis.
AB  - We report a patient with AH amyloidosis associated with lymphoplasmacytic
      leukemia that has remained in a stable state with a nephrotic syndrome for 17
      months since the commencement of cyclic rituximab therapy aimed at suppression of
      pathogenetic gamma heavy chains. Free light chains in serum and CD20-positive
      cells in peripheral blood were useful as hematological markers in the patient.
      Rituximab might be a potent therapeutic option for AH amyloidosis associated with
      a B-cell lymphoproliferative disorder.

PMID- 19590994
TI  - Compassion satisfaction, compassion fatigue, and burnout in a national sample of
      trauma treatment therapists.
AB  - For behavioral health professionals working with traumatized clients, continuous
      and prolonged exposure to the stress of working with the myriad of trauma-related
      stressors experienced by their clients can lead to various responses including
      burnout, compassion fatigue, and compassion satisfaction. The present study
      investigates the impact of using evidence-based practices on compassion fatigue,
      burnout, and compassion satisfaction in a random, national sample of self
      identified trauma specialists (N=532). The 30-item Professional Quality of Life
      Scale (Stamm, 2005) and the 19-item Trauma Practices Questionnaire (Craig &
      Sprang, 2009) were included in a survey to licensed social workers and
      psychologists from professional membership rosters. Age and years of experience
      proved to be powerful predictors of only two of the three criterion variables,
      with younger professionals reporting higher levels of burnout and more
      experienced providers endorsing higher levels of compassion satisfaction. The
      utilization of evidence-based practices predicted statistically significant
      decreases in compassion fatigue and burnout, and increases in compassion
      satisfaction. The utility of these findings in understanding the process of
      trauma transmission between therapist and client as well as directions for future
      research are discussed.

PMID- 19590995
TI  - Sociodemographic and psychopathological risk factors for repetition of attempted
      suicide: a 5-year follow-up study.
AB  - The present study examines the association between repetition of suicide attempts
      and sociodemographic and psychopathological characteristics of patients during a
      5-year follow-up period. Participants were 874 suicide attempters referred to the
      University Hospital of Ghent, among whom 361 (41.3%) patients were available for
      follow-up analysis. Within 5 years, 29.2% of those admitted for an index suicide
      attempt repeated non-fatal suicidal behavior. Repetition of suicidal behavior was
      associated with high scores on measures of psychopathology. In addition, the risk
      of repetition was increased if the patient was female, aged between 20 and 49,
      and had a lower education. Multivariate analysis showed significant results for
      age, the Buglass & Horton Risk of Repetition Scale and for anxiety. Repetition of
      suicidal behavior is associated with high anxiety, severe depression, more
      psychiatric symptoms and is increased in young patients.

PMID- 19590996
TI  - Life-time adversities, reported thirteen years after a suicide attempt:
      relationship to recovery, 5HTTLPR genotype, and past and present morbidity.
AB  - In this study, we investigated how adversities related to past and present
      morbidity, and genotype. Forty-two, suicide attempters and 22 matched control
      patients were followed-up after 13 years. Life-time adversities were explored in
      an interview, and the patients were reassessed psychiatrically. The serotonin
      transporter-linked promotor region (5-HTTLPR) was typed. More adversities were
      reported by suicide attempters than controls, and by still-ill than recovered
      suicide attempters. Adversities reported at follow-up were related to psychiatric
      morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR,
      genotype was associated with reported adversities, but not chances of recovery.
      Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not
      affect long-term recovery.

PMID- 19590997
TI  - Suicide ideation among college students: a multivariate analysis.
AB  - The goal of this study was to develop a multi-dimensional model that might
      explain suicide ideation among college students. Face-to-face interviews were
      conducted with 1,249 first-year college students. An estimated 6%(wt) of first
      year students at this university had current suicide ideation. Depressive
      symptoms, low social support, affective dysregulation, and father-child conflict
      were each independently associated with suicide ideation. Only 40%(wt) of
      individuals with suicide ideation were classified as depressed according to
      standard criteria. In the group who reported low levels of depressive symptoms,
      low social support and affective dysregulation were important predictors of
      suicide ideation. Alcohol use disorder was also independently associated with
      suicide ideation, while parental conflict was not. Results highlight potential
      targets for early intervention among college students.

PMID- 19590999
TI  - Dialectical behavior therapy-based skills training for family members of suicide
      attempters.
AB  - This pilot study evaluated the effect of Family Connections (FC), a Dialectical
      Behavior Therapy-based manualized skills training program, for family members of
      suicide attempters. The DBT-based skills training program aims to enhance the
      knowledge of wide range research based aspects of suicidal behavior and treatment
      recommendations. Furthermore it includes skills training for interpersonal
      relationships and also offers family members an opportunity to share their
      experiences. Thirteen participants completed the 9-week program with pre- and
      post self-report questionnaires. The results showed significant reduction in
      burden, improved psychic health and an increase in well-being regarding the
      relation with the patient. These results provide support for the need and
      importance of a DBT-based skills training program addressed specifically to
      family members of suicide attempters.

PMID- 19590998
TI  - Are high-lethality suicide attempters with bipolar disorder a distinct phenotype?
AB  - Because Bipolar Disorder (BD) individuals making highly lethal suicide attempts
      have greater injury burden and risk for suicide, early identification is
      critical. BD patients were classified as high- or low-lethality attempters. High
      lethality attempts required inpatient medical treatment. Mixed effects logistic
      regression models and permutation analyses examined correlations between
      lethality, number, and order of attempts. High-lethality attempters reported
      greater suicidal intent and more previous attempts. Multiple attempters showed no
      pattern of incremental lethality increase with subsequent attempts, but
      individuals with early high-lethality attempts more often made high-lethality
      attempts later. A subset of high-lethality attempters make only high-lethality
      attempts. However, presence of previous low-lethality attempts does not indicate
      that risk for more lethal, possibly successful, attempts is reduced.

PMID- 19590986
TI  - Evidence for the use of intravenous immunoglobulins--a review of the literature.
AB  - Intravenous immunoglobulins (IVIg) were first introduced in the middle of the
      twentieth century for the treatment of primary immunodeficiencies. In 1981, Paul
      Imbach noticed an improvement of immune-mediated thrombocytopenia, in patients
      receiving IVIg for immunodeficiencies. This opened a new era for the treatment of
      autoimmune conditions with IVIg. Since then, IVIg has become an important
      treatment option in a wide spectrum of diseases, including autoimmune and acute
      inflammatory conditions, most of them off-label (not included in the US Food and
      Drug Administration recommendation). A panel of immunologists and internists with
      experience in IVIg therapy reviewed the medical literature for published data
      concerning treatment with IVIg. The quality of evidence was assessed, and a
      summary of the available relevant literature in each disease was given. To our
      knowledge, this is the first all-inclusive comprehensive review, developed to
      assist the clinician when considering the use of IVIg in autoimmune diseases,
      immune deficiencies, and other conditions.

PMID- 19591000
TI  - Examining suicide-risk individuals who go online for suicide-related purposes.
AB  - The objective of this study was to better help those in suicidal crisis by
      examining the types of suicide-risk individuals who make use of the Internet in
      relation to their suicidal problems. An anonymous online survey examined suicide
      risk individuals who went online for suicide-related purposes (n = 165) and a
      reference group of suicide-risk individuals with no such experience (n = 125).
      Suicide-risk individuals who went online for suicide-related purposes, compared
      with online users who did not, reported greater suicide-risk symptoms, were less
      likely to seek help, and perceived less social support. Online, many reported
      more support, felt less alienated, believed they reduced their suicidality, but
      also sought suicide methods and were likely to visit "pro suicide" sites.
      Implications include designing help sites that allow peer-to-peer communications
      and anonymous professional support.

PMID- 19591002
TI  - Suicide rates and status integration in America.
AB  - In order to better understand how educational attainment and marital status
      impact the likelihood of suicide among various age-sex-race/ethnic groups in
      America, Gibbs and Martin's theory of Status Integration is tested. The
      distribution of suicide rates from 1991-1994 in the United States for people of
      different status categories of age, gender, education, marital status, and
      race/ethnicity is compared to the distribution of the population in these same
      status categories. The distribution of suicide rates for the status
      configurations analyzed herein differ significantly from the population
      distribution for these same status configurations. Gibbs and Martin's theory
      accurately describes variation in suicide rates.

PMID- 19591001
TI  - Correlates of suicidal behaviors among Asian Americans.
AB  - This study examines the correlates of suicidal ideation, suicide plan and suicide
      attempt among Asian Americans focusing on nativity and gender. Analyses are
      performed on data from the National Latino and Asian American Study (N = 2095),
      the first ever study conducted on the mental health of a national sample of Asian
      Americans. The sample is comprised of adults with 998 men (47%) and 1,097 (53%)
      women. Analysis of weighted lifetime prevalence of suicidal behaviors revealed
      that U.S.-born Asian American women had higher prevalence of suicidal ideation
      and suicide plan than U.S.-born Asian American men and immigrant Asian American
      men and women. In multivariate analyses controlling for socio-demographic
      differences such as ethnicity, marital status and income, differences in suicidal
      behaviors are found only between U.S.-born women and U.S.-born men. The findings
      demonstrate the need to disaggregate data by immigrant status as well as socio
      demographic correlates.

PMID- 19591003
TI  - Suicide risk after homicide in Sweden.
AB  - Temporal aspects of suicide risk after homicide using survival analytic method
      are not fully known and the risk estimates are almost exclusively based on
      studies of less than 10 years of follow-up. We investigated a population based
      cohort of 167 Swedish homicide offenders from 1970 to 1980 for which causes of
      death during the following minimum of 22 years were investigated using survival
      analysis. Twenty nine suicides (17.4%) occurred during the follow-up representing
      30% of the total mortality. A high proportion of suicides (72%) occurred early,
      within 2 years after the homicide. The suicides continued to accumulate during
      the following decades after the homicide and the cumulative suicide risk was
      18.6%. A very high proportion of violent suicide method (86%) was found. Suicide
      mortality was heavily skewed towards the first years after the homicide. Homicide
      offenders have very high short term suicide risk and the suicide risk persists
      over the entire adult lifespan. Homicide is a strong predictor of future suicide
      and similar biological mechanisms may be involved in violent criminality and
      suicidal behavior.

PMID- 19591004
TI  - The loneliness experiences of young adults with cerebral palsy who use
      alternative and augmentative communication.
AB  - Young adults with cerebral palsy who use augmentative and alternative
      communication (AAC) systems may be at increased risk of loneliness due to the
      additional challenges they experience with communication. Six young adults, aged
      24-30 years, who used AAC and had cerebral palsy, participated in in-depth
      interviews to explore their experiences of loneliness as they made the transition
      into adulthood. A total of five major themes in the data were identified using
      the constant comparative method of analysis. Three of these themes were discussed
      by all participants: (a) Support Networks, (b) AAC System Use, and (c)
      Technology. The authors concluded that these three themes were most important in
      understanding the experiences of loneliness of the young adults with cerebral
      palsy who participated in this study.

PMID- 19591005
TI  - Gender, socio-economic variables and target organ damage in new-diagnosed
      hypertensive patients.
AB  - The aim of the study as to ascertain whether gender and socio-economic variables
      can explain differences in the degree of severity of hypertension (HT) at the
      time of diagnosis. Patients were recently diagnosed and never-treated
      hypertensives, seen in primary care sites and aged 15-75. This study also
      included a cohort of normotensive patients. All individuals were invited to
      respond a questionnaire to collect socio-demographic and socio-economic data.
      Target organ damage (TOD) is considered a marker of severity. Three hundred and
      eighty-eight individuals responded to the questionnaire, 277 hypertensive, 111
      normotensive. In an ordered probit model, the odds ratio of presenting with more
      than one TOD were: Aged >67 (OR=1.22; 1.06-1.38), being a smoker (OR=1.21; 1.02
      1.40) or ex-smoker (OR=2.89; 1.27-4.51), primary school education (OR=2.17; 1.47
      2.87), being male (OR=0.75; 0.59-0.90), being an agricultural worker (OR=0.03;
      0.00-0.05) or a salaried professional (OR=0.96; 0.94-0.99). The results show
      differences in the severity of the HT in the initial assessment of the patient
      according to gender or other socio-economic variables. It is particularly
      important at the time of carrying out the diagnosis and the HT assessment.

PMID- 19591008
TI  - The effects of hormone replacement therapy on autoimmune disease: rheumatoid
      arthritis and systemic lupus erythematosus.
AB  - Autoimmune diseases are generally more common in women than men; however, there
      is no simple explanation for this. Sex hormones, especially estrogen (but also
      prolactin and testosterone), play important roles in these diseases. Estrogens
      are generally considered to enhance autoimmunity and have multiple effects on the
      immune system through various cell types and molecular pathways. There is much
      evidence supporting the role of estrogen in the pathogenesis of systemic lupus
      erythematosus (SLE): the disease occurs much more frequently in women, especially
      during the years of child-bearing potential, and commonly flares during
      pregnancy. The relationship between estrogen and the development of SLE is
      complex, however. Exogenous estrogens have been historically avoided in women
      with SLE due to the widely held view that they could activate disease and their
      use remains controversial. Current evidence from prospective trials suggests that
      there may be a small increased risk of mild/moderate flares in women with SLE
      taking hormone replacement therapy (HRT), but the risk of major flare does not
      appear to be increased. In rheumatoid arthritis, HRT does not appear to be
      associated with an increased risk of disease flare and may actually improve
      disease activity. In all individuals with autoimmune disease, the risk of venous
      thrombosis associated with oral HRT is an important factor that should also be
      considered.

PMID- 19591007
TI  - Effect of non-oral estrogen on risk markers for metabolic syndrome in early
      surgically menopausal women.
AB  - OBJECTIVE: Postmenopausal women are at an increased risk of cardiovascular
      disease and metabolic syndrome as many risk factors are aggravated by menopause.
      Elevated levels of homocysteine, triglyceride and asymmetric dimethylarginine
      (ADMA) have been recognized as risk factors for metabolic syndrome. The present
      study aimed to investigate the effect of transdermal estrogen treatment on serum
      levels of atherogenic amino acids, homocysteine, triglyceride, high density
      lipoprotein (HDL) cholesterol and ADMA in women with surgical menopause. METHODS:
      A prospective study was conducted in 85 surgically menopausal Turkish women at
      the Department of Menopause of Dr Zekai Tahir Burak Women's Health Research and
      Education Hospital between March 2007 and March 2008. Subjects were divided into
      two groups: a treatment group (Group 1) and control (Group 2). Group 1 (n = 46)
      received transdermal estrogen while Group 2 (n = 39) received no treatment. Body
      mass index (BMI) and levels of serum homocysteine, ADMA, triglyceride and HDL
      cholesterol were analyzed postoperatively at the first visit (baseline) and 6th
      months. RESULTS: The two groups did not differ in age, baseline BMI and levels of
      ADMA, homocysteine and triglyceride. In Group 1, values of serum ADMA,
      homocysteine, triglyceride and HDL cholesterol levels were not different at
      baseline and at the 6-month visit (p = 0.996, p = 0.564, p = 0.113 and p = 0.173,
      respectively). On the other hand, the baseline and the 6th month measurements of
      serum ADMA, homocysteine and HDL cholesterol levels were significantly different
      in Group 2 (p = 0.001, p = 0.001, and p = 0.023, respectively). CONCLUSION:
      Transdermal estrogen treatment has a protective effect against the risk factors
      of metabolic syndrome (homocysteine, ADMA, HDL cholesterol) in surgically
      menopausal patients who have undergone surgery in the early premenopausal period.

PMID- 19591006
TI  - Clinical parameters linked with malignancy in endometrial polyps.
AB  - AIM: To investigate the association of different clinical parameters with the
      histological diagnosis and the prevalence of premalignant and malignant
      endometrial polyps. METHOD: The study included 516 cases from January 2002 to
      December 2006. Possible risk factors such as age, menopause status, abnormal
      bleeding, obesity, hypertension, diabetes mellitus, hormone therapy, use of
      tamoxifen and size of polyp were investigated in relation to their association
      with the malignant potential of endometrial polyps. RESULTS: All cases of
      endometrial polyps underwent hysteroscopic resection; 96.9% of the cases were
      benign, 1.2% premalignant and 1.9% malignant. Premalignant and malignant
      endometrial polyps were significantly associated with advanced age (>60 years),
      menopause, obesity and diabetes. The malignant polyps were analyzed to eight
      endometrioid, one serous and one clear cell carcinoma. CONCLUSION: The prevalence
      of premalignant and malignant endometrial polyps is very low. Advanced age,
      menopause, obesity and diabetes increase the risk of endometrial polyp
      malignancy.

PMID- 19591010
TI  - Dose effects of oral estradiol on bone mineral density in Japanese women with
      osteoporosis.
AB  - OBJECTIVES: This 2-year study compared 0.5 and 1.0 mg oral estradiol (E(2)), with
      or without levonorgestrel (LNG), for the treatment of postmenopausal osteoporosis
      in Japanese women. METHODS: Japanese women with osteoporosis after natural
      menopause or bilateral oophorectomy were randomized to receive E(2) 0.5 or 1.0
      mg/day with LNG 40 microg as required, or placebo, for 52 weeks. Women treated
      with E(2) in the first year continued therapy at the same doses in the second
      year. Efficacy, safety and pharmacokinetics were assessed. RESULTS: There were 73
      women randomized to E(2) 0.5 mg, 157 to E(2) 1.0 mg and 79 to placebo. Lumbar
      bone mineral density at 52 weeks increased significantly more with E(2) 1.0 mg (p
      < 0.001) and 0.5 mg (p < 0.001) than with placebo (no change). After 2 years, a
      10% increase in bone mineral density with E(2) 1.0 mg was significantly greater
      than with E(2) 0.5 mg (8%; p = 0.008). E(2) was associated with an acceptable
      safety and tolerability profile, with slightly more adverse events with E(2) 1.0
      than 0.5 mg. Serum E(2) concentration increased in a dose-dependent manner.
      CONCLUSION: This study showed that E(2), at both 1.0 mg and 0.5 mg doses, was
      effective in increasing bone mineral density with an acceptable safety and
      tolerability profile in Japanese postmenopausal women with osteoporosis but that
      the bone mineral density response was higher with the 1.0 mg dose.

PMID- 19591012
TI  - Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible
      adaptation mechanism of redox imbalance.
AB  - Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress.
      Unexpectedly, it was found that sarcoplasmic reticulum Ca(2 +)-ATPase (SERCA)
      activity was elevated in muscles of rats with AA compared to controls, suggesting
      possible conformational changes in the enzyme. There was no alteration in the
      nucleotide binding site but rather in the transmembrane domain according to the
      tryptophan polar/non-polar fluorescence ratio. Higher relative expression of
      SERCA, higher content of nitrotyrosine but no increase in phospholipid oxidation
      in AA SR was found. In vitro treatments of SR with HOCl showed that in AA animals
      SERCA activity was more susceptible to oxidative stress, but SR phospholipids
      were more resistant and SERCA could also be activated by phosphatidic acid. It
      was concluded that increased SERCA activity in AA was due to increased levels of
      SERCA protein and structural changes to the protein, probably induced by direct
      and specific oxidation involving reactive nitrogen species.

PMID- 19591013
TI  - Protective mechanisms of NO preconditioning against NO-induced apoptosis in H9c2
      cells: role of PKC and COX-2.
AB  - Cardiomyocyte apoptosis is involved in several cardiovascular diseases, including
      ischemia, hypertrophy and heart failure. Nitric oxide (NO) signalling is crucial
      in the regulation of cardiomyocyte apoptosis, capable of both inducing and
      preventing apoptosis depending upon the level of NO production. Growing evidence
      suggests that NO preconditioning has cardioprotective effects, but the mechanism
      remains unclear. The purpose of this study was to elucidate how NO
      preconditioning inhibits subsequent NO-induced apoptosis in H9c2 cells. According
      to the data, preconditioning with a low concentration of sodium nitroprusside
      (SNP, 0.3 mM) inhibited subsequent high-concentration-SNP (1.5 mM)-induced
      apoptosis and this effect was reversed by the protein kinase C (PKC) inhibitor
      chelerythrine and the cyclooxygenase-2 (COX-2) inhibitor rofecoxib. Low
      concentration-SNP-mediated protection involved extracellular signal regulated
      kinase 1/2 (ERK1/2), a signal transducers and activators of transcription 1/3
      (STAT1/3) activation and increased COX-2 expression. Activation of ERK1/2 and
      STAT1/3 was abolished by chelerythrine. However, COX-2 expression was not
      inhibited, implying that the COX-2-mediated protective effect occurred via a PKC
      independent pathway. The results showed that low-concentration-SNP
      preconditioning suppresses subsequent high-concentration-SNP-induced apoptosis by
      ERK1/2-STAT 1/3 activation via PKC-dependent mechanisms in H9c2 cells. COX-2 also
      plays a role in NO-induced preconditioning, but is independent of PKC.

PMID- 19591014
TI  - DNA damage in response to an Ironman triathlon.
AB  - The major aims of this study were to investigate the effect of an Ironman
      triathlon on DNA migration in the single cell gel electrophoresis assay,
      apoptosis and necrosis in the cytokinesis-block micronucleus cytome assay with
      lymphocytes and on changes of total antioxidant capacity in plasma. Blood samples
      were taken 2 days (d) before, within 20 min, 1 d, 5 d and 19 d post-race. The
      level of strand breaks decreased (p<0.05) immediately after the race, then
      increased (p<0.01) 1 d post-race and declined (p<0.01) until 19 d post-race.
      Apoptotic and necrotic cells decreased (p<0.01) and the total antioxidant status
      increased (p<0.01) immediately after the race. The results indicate that ultra
      endurance exercise does not cause prolonged DNA damage in well-trained male
      athletes.

PMID- 19591015
TI  - Myostatin in tendon maintenance and repair.
AB  - Myostatin, a negative regulator of muscle growth, has recently been found to be
      expressed in tendons. Myostatin-deficient mice have weak and brittle tendons,
      which suggest that myostatin could be important for tendon maintenance.
      Follistatin expression in the callus tissue after tendon transection is
      influenced by loading. We found that follistatin antagonises myostatin, but not
      GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in
      soft tissue, we transected 64 rat Achilles tendons and studied the gene
      expression for myostatin and its receptors at four different time-points during
      healing. Intact tendons were also studied. All samples were studied with or
      without mechanical loading. Unloading was achieved with botulinum toxin
      injections in the calf muscles. The expression of the myostatin gene was more
      than 40 times higher in intact tendons than in the callus tissue during tendon
      healing. The expression of myostatin was also influenced by loading status in
      both intact and healing tendons. Thereafter, we measured the mechanical
      properties of healing tendons after local myostatin administration. This
      treatment increased the volume and the contraction of the callus after 8 days,
      but did not improve its strength. Our results indicate that myostatin plays a
      positive role in tendon maintenance and that exogenous protein administration
      stimulates proliferation and growth of early repair tissue. However, no effect on
      further development towards connective tissue formation was found.

PMID- 19591016
TI  - Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post
      partum and review of literature.
AB  - Cushing's syndrome due to AdrenoCorticoTropic Hormone (ACTH)-secreting
      pheochromocytoma has been rarely reported during pregnancy and post-partum. We
      report the case of a 30-year-old woman who presented 3 months after delivery
      acute psychiatric signs and rapid progressive features of Cushing's syndrome.
      Hormonal tests confirmed ACTH-dependant Cushing's syndrome. A computed tomography
      scan revealed a 25 x 30 mm tumoral mass in the left adrenal gland and octreoscan
      scintigraphy showed only an uptake of the radiolabelled octreotide by the adrenal
      tumor. Fractionated 24-h urinary catecholamines and metanephrines were in the
      normal range, except for slightly increased adrenalin levels. A left laparoscopic
      adrenalectomy was performed with acute pulmonary oedema following the anesthesia.
      Histological examination revealed a 3.5 x 2.5 cm adrenal tumor consistent with a
      pheochromocytoma without signs of malignancy. The tumor cells immunostained for
      ACTH and diffuse hyperplasia of adrenocortical cells was observed. After surgery
      and short stay in intensive care unit, clinical and biological signs rapidly
      improved and both anti-hypertensive treatment and insulin injections were
      withdrawn. Genetic testing did not reveal germline mutations in RET
      protooncogene, Von Hippel Lindau and succinate deshydrogenase genes.

PMID- 19591017
TI  - The role of genes in the polycystic ovary syndrome: predisposition and
      mechanisms.
AB  - The polycystic ovary syndrome (PCOS), mainly characterized by clinical and/or
      biochemical hyperandrogenism, ovarian dysfunction and/or polycystic morphology as
      well as associated metabolic disorders, is the most common endocrine disorder in
      women of reproductive age. The familial clustering of PCOS cases and the
      accumulating evidence that the interaction between multiple genetic and
      environmental factors is necessary for the development of the syndrome, has
      triggered the conduct of genetic studies on PCOS. These studies have focused on
      many genetic polymorphisms, investigating their possible positive or negative
      correlation with the syndrome. The related genes can be grouped in four
      categories: those related with insulin resistance, those that interfere with the
      biosynthesis and the action of androgens, those that encode inflammatory
      cytokines and other candidate genes. Despite the progress that has been made in
      the elucidation of the genetic mechanisms of the PCOS, the genetic studies on the
      syndrome still face many obstacles and challenges. Further studies are needed, in
      order to shed new light in the pathogenesis of the syndrome, which will allow for
      new approaches in the diagnostics and therapeutics of PCOS.

PMID- 19591018
TI  - Isoflavones are safe compounds for therapeutical applications - evaluation of in
      vitro data.
AB  - Isoflavone-rich food and food supplements have gained increasing popularity also
      in the Western world. Their weak estrogenic effect has been considered as a
      potential risk, although all epidemiological studies and clinical trials show a
      significant cancer protection and decreased risk of cardiovascular diseases. In
      vitro data suggest that the concerted action of the isoflavones and their
      metabolites show antiproliferative behaviour, reduce angiogenesis, reduce tumor
      progression and exert antiinflammatory effects. For the evaluation of the
      biological effects, special emphasis has to be put on the concerted action
      between the isoflavones and their metabolites. For instance, while isolated
      genistein shows some growth promoting effect at low concentrations, the
      metabolite equol or soy extract show growth retardation as well as higher
      concentrations of genistein do. The isoflavones have multiple affinities to other
      members of the steroid hormone receptor superfamily. The beneficial effect on
      metabolic diseases and weight reduction by isoflavone consumption can be partly
      explained by its affinity for the PPAR family. In light of the in vitro
      experiments, together with the epidemiological observations and the clinical
      experience, isoflavones can be considered as safe compounds and their consumption
      as food and food supplements has to be promoted.

PMID- 19591019
TI  - The scourge of methamphetamine.

PMID- 19591020
TI  - Perceptions of the relationship between mental health professionals and family
      caregivers: has there been any change?
AB  - A number of international studies have highlighted family caregivers' (FCGs')
      dissatisfaction with their relationship with mental health professionals (MHPs)
      when providing care for mentally ill family members. However, few studies have
      explored the mental health professionals' perspective of this relationship. This
      study explored both FCGs' and MHPs' perspectives. Semi-structured interviews were
      conducted with seven FCGs and seven MHPs from two different geographical areas of
      New Zealand. Thematic analysis of these interviews revealed four distinct MHP
      themes and five FCG themes. The themes illuminate incongruence between MHPs'
      intentions to form a positive working relationship with families and the FCGs'
      mainly negative experiences of this relationship.

PMID- 19591022
TI  - Hydrotherapy in state mental hospitals in the mid-twentieth century.
AB  - This research describes nurses' experiences in administering "the water cure,"
      hot or cold wet sheet packs, and continuous tub baths in state mental hospitals
      during the early twentieth century. Student and graduate nurses were required to
      demonstrate competence in hydrotherapy treatments used to calm agitated or manic
      patients in the era before neuroleptics. The nurses interviewed for this study
      indicated that, although labor intensive, hydrotherapy worked, at least
      temporarily. Although no longer used in state hospitals, hydrotherapy is
      regaining popularity with the general public and may serve as an adjunct to
      pharmacological treatments to calm hospitalized patients in the future.

PMID- 19591021
TI  - The importance of medication in consumer definitions of recovery from serious
      mental illness: a qualitative study.
AB  - The role of medication in the recovery of mental health consumers is important.
      In the context of a multi-site Canadian study on the meaning of recovery, five
      themes related to medication and recovery emerged from qualitative interviews
      with 60 consumers. For these consumers, recovery meant: finding a medication that
      works; taking medication in combination with services and supports; complying
      with medication; having a say about medication; and living without medication.
      Findings underlined consumers' need to communicate their concerns around
      medication and be supported in developing self-management strategies and more
      collaborative relationships with providers. The study suggests an expanded role
      for nursing practice in these areas.

PMID- 19591023
TI  - Exploring differences between community-based women and men with a history of
      mental illness.
AB  - Relatively little is understood concerning the role of gender in persons with a
      history of mental illness residing in the community. This paper aims to explore
      gender's effect using data from the Community Research University Alliance
      project entitled, Mental Health and Housing. The primary five-year longitudinal
      study examined housing situations for psychiatric consumer/survivors in a mid
      size, central Canadian region in an effort to improve the number and quality of
      appropriate housing situations. Data from 887 subjects in the original research
      underwent secondary analysis with particular relevance to differences between
      gender and indicators of health status including psychiatric history, levels of
      functioning, personal strengths and resources, and illness severity. Results of
      the secondary analysis found male and female differences that corroborated
      previous research. More women are housed than men, more women with mental illness
      were coupled than men, men have fewer social supports, and men have more
      substance abuse issues than women. These findings suggest health services within
      the community must consider these sex differences if they wish to properly assist
      Canadian individuals diagnosed with mental illnesses.

PMID- 19591025
TI  - Mental illness stigma and disclosure: consequences of coming out of the closet.
AB  - The present study investigated disclosure patterns among mental health consumers
      (N = 500) and examined the relationships among disclosure, perceived
      stigmatization, perceived social support, and self-esteem. Results suggest that
      selective disclosure optimizes social support and limits stigmatization.
      Perceived stigmatization has a detrimental impact on self-esteem, especially for
      those who are relatively open about their mental disorder.

PMID- 19591024
TI  - Communication and human patient simulation in psychiatric nursing.
AB  - Communication is an integral component of nursing education and has been shown to
      improve health outcomes, patient compliance, and patient satisfaction.
      Psychiatric nursing emphasizes knowledge and utilization of communication skills.
      Nursing students often express anxiety and lack of confidence regarding
      communicating with patients diagnosed with psychiatric illnesses. Human patient
      simulation is one method that may be used for students to practice and become
      proficient with communication skills in a simulated environment. The authors of
      this article provide an overview of communication and psychiatric nursing as well
      as review of the current research related to the use of human patient simulation
      in nursing education.

PMID- 19591026
TI  - Renewing everyday hope: the hope experience of family caregivers of persons with
      dementia.
AB  - The purpose of this grounded theory study was to explore the experience of hope
      for family members caring for a person with dementia. Seventeen family members
      caring for persons with dementia were interviewed. The participants described
      their hope as the possibility of a positive future within their daily lives and
      in the social context of grief and loss, stress, fatigue, and constantly dealing
      with challenging behaviours of the person with dementia. The main concern of the
      study participants was "fading hope," which they dealt with by "renewing every
      day hope" through (a) coming to terms, (b) finding positives, and (c) seeing
      possibilities.

PMID- 19591027
TI  - Dementia, ethnicity, and culture.

PMID- 19591028
TI  - Using case studies to define nursing informatics interoperability.

PMID- 19591029
TI  - Nurses, mental health, and hard economic times.

PMID- 19591032
TI  - Autogynephilia in women.
AB  - Autogynephilia, an erotic interest in the thought or image of oneself as a woman,
      has been described as a sexual interest of some male-to-female transsexuals
      (MTFs); the term has not been applied to natal women. To test the possibility
      that natal women also experience autogynephilia, an Autogynephilia Scale for
      Women (ASW) was created from items used to categorize MTFs as autogynephilic in
      other studies. A questionnaire that included the ASW was distributed to a sample
      of 51 professional women employed at an urban hospital; 29 completed
      questionnaires were returned for analysis. By the common definition of ever
      having erotic arousal to the thought or image of oneself as a woman, 93% of the
      respondents would be classified as autogynephilic. Using a more rigorous
      definition of "frequent" arousal to multiple items, 28% would be classified as
      autogynephilic. The implications of these findings are discussed concerning the
      sexuality of women and the meaning of autogynephilia for MTFs.

PMID- 19591033
TI  - An exploration of the experience of lesbians with chronic illness.
AB  - An exploration of the challenges facing lesbians with chronic conditions and
      their coping strategies was investigated by examining the experiences of
      participants who were clients of a volunteer organization serving chronically ill
      lesbians. This article reports the results associated with those challenges, with
      its ultimate goal being and to assess the effectiveness of current services.
      Using the participant observation method, as employed by O'Toole (2000), the
      analysis was based on multiple data sources and 10 years experience within the
      volunteer organization, including 3 years in direct client support. A qualitative
      method served as the primary focus for the study. The quantitative method
      preceded the qualitative method and provided limited supporting data. The total
      number of participants included all past and current clients, but the number
      participating in each data source varied. Qualitative sources included archival
      structured interviews (n = 69), taped interviews (n = 5-6), and extensive
      comments written in response to the quantitative surveys (n = 14). The
      quantitative measures (n = 14) included the researcher-developed Chronic
      Conditions Challenges Checklist (C4) and the Short Form of the McGill Pain
      Questionnaire ([SF-MPQ]; Melzack, 1998). A content analysis of all data sources
      found a number of challenges that met the criteria of being identified in at
      least two data sources and across multiple participants. Challenges included
      those related to the disease process (i.e., pain, fatigue, and decreases in
      mobility) to impacts of the condition (financial security, ability to
      participate, support from family of origin and independence, loneliness, and
      issues related to mental health). Challenges were discussed in terms of those
      that are similar to and different from other women suffering from chronic
      illness, as well as their relevance to related literature.

PMID- 19591034
TI  - Buffy the Vampire Slayer and Xena: Warrior Princess: reception of the texts by a
      sample of lesbian fans and web site users.
AB  - This qualitative study of television reception examined the ways in which a
      sample of lesbian fans of Buffy the Vampire Slayer and Xena: Warrior Princess
      incorporated their experiences as viewers, fans, and Internet users with relation
      to their sexual identity as lesbians. Specifically, this study examined the ways
      in which participants used these television programs to inform their sexual
      identity development. Results indicated that participants used television and the
      Internet to normalize and affirm lesbian experience, to decrease negative
      feelings regarding their lesbian identities, and to decrease social isolation.

PMID- 19591035
TI  - Interiorized homophobia, identity dynamics and gender typization. Hypothesizing a
      third gender role in Italian LGB individuals.
AB  - With this research, we explored the relation between (a) internalized homophobia,
      (b) lesbian, gay male, and bisexual (LGB) social identity statuses (along with
      the Marcia model), and (c) gender typization (along with Bem gender schema
      theory) of an Italian online LGB sample. Results show how the identity process of
      exploration is a risk factor in relation to internalized homophobia, whereas
      commitment is a protective factor. Against the authors' expectations, data
      indicate that androgynous, non-heterosexual individuals are mostly in a
      foreclosure identity status, while the typed ones are in an acquisition status
      and more protected against homophobia. This suggests that the androgynous social
      representation of homosexuality for non-heterosexual individuals is an
      alternative gender role more socially available to them.

PMID- 19591036
TI  - The last book-burning trial of the twentieth century: the Stalstrom dissertation
      and the challenge of homophobic authority.
AB  - Anti-homosexual (also known as homophobic) values, attitudes, and beliefs thrive,
      in part, on misinformation and by restricting discussion that might challenge
      such views. While this was more typical of academic environments in the 1950s,
      partly because the study of homosexuality was largely based on clinical or
      correctional populations, academic environments have usually been in the
      forefront of empirical and social discussion of sexuality. Preventing such
      discussion (which maintains outdated pathological or criminal theories of
      homosexuality), thus becomes a significant agenda of those attempting to maintain
      anti-homosexual attitudes. Further, when anti-homosexual attitudes have
      characterized a particular professional group, prevention of any discussion that
      may reveal that the position of that group was without empirical foundation also
      serves the function of maintaining their authority as "experts" and allows
      restrictions on the human rights of homosexual or bisexual individuals to go
      unchallenged. Rarely, however, has this resulted in a direct attempt to silence
      academic discussion, through the invocation of legal sanctions. This article
      looks at the history of such an attempt in Finland, where an adherent of
      classical psychoanalysis fought to challenge progress and reverse the tide of
      scientific and clinical evidence that judged homosexuality to be non
      pathological.

PMID- 19591037
TI  - The relationship between anxiety and sexual functioning in lesbians and
      heterosexual women.
AB  - The association between anxiety and sexual functioning was studied in relation to
      women's sexual orientation. Participants in lesbian relationships (n = 42) and
      heterosexual relationships (n = 78) completed the Multidimensional Anxiety
      Questionnaire and Female Sexual Function Index. No difference was found between
      groups on the anxiety measure, but lesbians scored higher than heterosexuals on
      sexual functioning scales for arousal and orgasm. Intercorrelations among sexual
      functioning scales were dissimilar for lesbians and heterosexuals. Among
      heterosexuals, anxiety was negatively correlated with overall sexual functioning,
      lubrication, orgasm, and pain, but among lesbians anxiety was uncorrelated with
      all sexual functioning variables.

PMID- 19591038
TI  - Sexual orientation and quality of life among university students from Cuba,
      Norway, India, and South Africa.
AB  - This article explores quality-of-life aspects among gay, lesbian, bisexual, and
      straight male and female students in Havana (Cuba), Tromso (Norway), Hisar
      (India), and Cape Town (South Africa). In the period 2004-2005, a questionnaire
      survey on sexuality, happiness, and life satisfaction was undertaken among 339
      students from the University of Havana, 144 students from the University of
      Tromso, 200 students from Guru Jambheswar University, and 189 students from the
      University of the Western Cape. The majority of the participants were straight
      and, in Hisar and Cape Town, few of those who regarded themselves as
      gay/lesbian/bisexual had engaged in sex with a person of the same gender. In all
      cities, straight men and women scored higher than gay, lesbian, and bisexual
      persons on the quality-of-life measures. Quality of life among gay/bisexual men
      and lesbian/bisexual women was higher in cultures with accepting attitudes toward
      homosexuality than in cultures with restrictive attitudes.

PMID- 19591040
TI  - Antigenicity of a type A influenza virus through comparison of hemagglutination
      inhibition and mass spectrometry immunoassays.
AB  - The antigenicity of a type A (H1N1) influenza strain has been characterised
      through the application of mass spectrometry (MS) and hemagglutination-inhibition
      immunoassays performed in parallel. Two monoclonal antibodies were found to be
      highly and equally specific in HI assays against influenza strain A/New
      Caledonia/20/99 while the MS immunoassay demonstrated that both antibodies
      recognise the same epitopic peptide localised to residues 225-232 of the
      hemagglutinin HA1 subunit whose C-terminal residues reside in close proximity to
      the receptor binding site. Both immunoassays showed no binding of a monoclonal
      antibody that recognizes the hemagglutinin antigen of type B strains.

PMID- 19591041
TI  - Animal-derived pharmaceutical proteins.
AB  - Livestock animals have made a significant contribution to human health and well
      being throughout humankind's history. A significant contribution of farm animals
      to human health are the longstanding use of bovine and porcine for production of
      insulin (for treatment of diabetes), gelatin (for pharmaceutical and other
      purposes), as well as horse and sheep antibody against natural venoms, toxins,
      drugs and microbial peptides. Gelatin being the biggest animal protein consumed
      in human health, follows with antibodies fragments. The chronic problem of animal
      derived therapeutics, especially those of high molecular weight, is the
      immunogenicity induction in addition to their biosafety. However, the
      invertebrates and lower vertebrates donate the human being a several crucial
      emergency saving life small-peptides or their analogs such as Refludan, Prialt,
      Exendin. Not only, but the farm animals are enormously using as models for novel
      surgical strategies, testing of biodegradable implants and sources of tissue
      replacements, such as skin and heart valves. Recently, they are being harnessing
      as bioreactor for production of biopharmaceutical related products through gene
      farming with efficiency far greater than any conventional microbial or cell
      culture production systems. Only 16 transgenic cows would be covering the
      worldwide needs from human growth hormone. The transgenic, especially animal,
      technology would be solving a several biopharmaceutical products disadvantages,
      such as cost, biosafety, immunogenicity and the availability dimensions.

PMID- 19591042
TI  - Definition of purified enzyme-linked immunosorbent assay antigens from the
      culture filtrate protein of Mycobacterium bovis by proteomic analysis.
AB  - Enzyme-linked immunosorbent assay (ELISA) has been developed as the ancillary
      diagnosis of bovine tuberculosis at ante-mortem to overcome the disadvantages of
      intradermal skin test. In this study, the antigenic proteins were purified,
      applied to bTB ELISA, and identified through proteomic analysis. Culture filtrate
      protein of Mycobacterium bovis was fractionated by MonoQ column chromatography,
      and examined the antigenicity by immunoblotting. The antigenic 20 kDa protein was
      in-gel digested and identified the antigenome by LTQ mass spectrometer and
      peptide match fingerprinting, which were MPB64, MPB70, MPB83, Fas, Smc, Nrp,
      RpoC, Transposase, LeuA, and MtbE. The 20 kDa protein exhibited the highest
      antigenicity to bTB positive cattle in ELISA and would be useful for bTB
      serological diagnosis.

PMID- 19591043
TI  - Drop in transforming growth factor-alpha and osteoprotegerin level in gingival
      crevicular fluid from patients with gingivitis.
AB  - Inflammatory mediators, especially cytokine, play a central role in the
      pathogenesis of gingivitis. The aim of this study was to identify and quantify
      the various growth factors, and cytokines in the gingival crevicular fluid (GCF)
      of patients with gingivitis, as compared with those of control subjects. The
      levels of cytokine in the samples were determined by their respective ELISAs. The
      transforming growth factor (TGF)-alpha and osteoprotegerin (OPG) level were
      significantly lower in patients with gingivitis than in the controls (p < 0.05).
      Also, there was a positive correlation between TGF-alpha and OPG levels (r =
      0.761). These results suggest that the decrease in growth factor TGF-alpha is
      associated with the pathophysiology and/or the progress of gingivitis.

PMID- 19591044
TI  - Validation and field assessment of a rapid lateral flow assay for detection of
      bovine antibody to Anaplasma marginale.
AB  - The lateral flow assay (LFA) is a rapid diagnostic test which may be performed
      under most conditions and is especially useful for field applications. This type
      of assay was applied to the detection of antibody to bovine Anaplasma marginale
      using sera from endemic areas and from areas which have been free from infection
      for more than 25 years. Briefly, the test uses recombinant A. marginale major
      surface protein 5 peptide (Msp5), immobilized on a cellulose acetate membrane. A
      serum sample is added to a pad containing a monoclonal antibody specific for
      bovine IgG(1), conjugated with colloidal gold, located at one end of the strip.
      The sample and gold conjugate are wicked along the membrane and if antibody is
      present in the serum, a visible line will form between the Msp5-antibody
      conjugate immune complex in minutes. An additional band of recombinant protein
      A/G was added to the membrane as a positive control reaction of the monoclonal
      antibody conjugate. For comparison, direct examination of blood smears and a
      nested polymerase chain reaction (PCR) were performed on some of the samples.
      Using samples from herds in one endemic area, the PCR gave a sensitivity value of
      9.2% while a commercial competitive enzyme immunoassay (CELISA) gave a
      sensitivity value of 17.2% and the LFA values of 20.5%. In a second endemic area,
      selected samples, all positive by direct examination gave a 71.7% sensitivity
      values with the PCR, 94.5% with the CELISA and 95.5% with the LFA. Using sera
      from a disease-free area, the specificity values were 100% for the PCR (testing a
      proportion of randomly selected samples), 99.5% for the CELISA and 98.0% for the
      LFA. It is envisaged that the validated LFA will be a useful tool for screening
      cattle moving from an area with infection to a disease-free area.

PMID- 19591045
TI  - A novel immuno-polymerase chain reaction protocol incorporating a highly purified
      streptavidin-DNA conjugate.
AB  - We have developed an immuno-polymerase chain reaction protocol which includes a
      highly purified streptavidin-DNA conjugate. The protocol comprises standard ELISA
      methodology and washing buffers together with a real-time PCR read-out system.
      The conjugate was employed in both indirect and capture assay formats, which can
      be completed in a single day using standard laboratory equipment. The immuno-PCR
      is reproducible, with a larger dynamic range and a sensitivity several orders of
      magnitude greater than the corresponding conventional ELISA. The minimum
      concentration of analyte detected was of the order of 1 pg/mL These
      characteristics should contribute to the adoption of immuno-PCR by research and
      clinical laboratories.

PMID- 19591046
TI  - Interference of Dermatophagoides' specific immunoglobulins G in the
      quantification of mite's specific immunoglobulins E.
AB  - In order to investigate the interference of specific IgG in the quantification of
      specific IgE, using the ImmunoCAP 250 system, we studied, in parallel, the
      interference by total adsorption of interferent and the classical method of
      adding interferent increasingly. Furthermore, to evaluate if the interference is
      affected by different solid phases, total extract of Dermatophagoides
      pteronyssinus and recombinant allergens of Dermatophagoides farinae were used.
      The results showed a statistical significant interference by IgG in the
      quantification of the specific IgE, but neither analytical nor clinical
      significant interference were observed. Therefore, this analytical system
      provides an accurate method for determination of the specific IgE concentration
      contributing to the allergic disease diagnosis quality.

PMID- 19591047
TI  - Dose-dependent inhibition of BrdU detection in the cell proliferation ELISA by
      culture medium proteins.
AB  - Determination of the proliferation rate of cultured mammalian cells is widely
      done using incorporation of 5-bromo-2-deoxyuridine into replicating DNA followed
      by quantitative detection in ELISA using a specific monoclonal antibody. However,
      we noted that the BrdU ELISA results did not correlate with viable cell counts
      when increasing concentrations of proteins were added to test their effects on
      proliferating cells. This observation suggested that proteins could interfere
      with BrdU incorporation or detection in the commercial BrdU ELISA used. We show
      here that the presence of exogenous proteins during cell fixation and DNA
      denaturation significantly inhibited BrdU detection presumably by coating the
      extracted DNA by a concentration-dependent protein film. A simple modification to
      the manufacturer's protocol (cell washing) permitted to avoid this interference
      and resulted in a significant increase of the assay sensitivity.

PMID- 19591048
TI  - Coupled fluid-wall modelling of steady flow in stenotic carotid arteries.
AB  - Arterial stenoses may cause critical blood flow and wall conditions leading to
      clinical complications. In this paper computational models of stenotic carotid
      arteries are proposed and the vessel wall collapse phenomenon is studied. The
      models are based on fluid-structure interactions (FSI) between blood and the
      arterial walls. Coupled finite element and computational fluid dynamics methods
      are used to simultaneously solve for stress and displacement in the solid, and
      for pressure, velocity and shear stress in the fluid domain. Results show high
      wall shear stress at the stenosis throat and low (negative) values accompanied by
      disturbed flow patterns downstream of the stenosis. The wall circumferential
      stress varies abruptly from tensile to compressive along the stenosis with high
      stress concentration on the plaque shoulders showing regions of possible plaque
      rupture. Wall compression and collapse are observed for severe cases. Post
      stenotic collapse of the arterial wall occurs for stenotic severity as low as
      50%, with the assumption that a given amount of blood flow needs to pass the
      stenotic artery; whereas if constant pressure drop should be maintained across a
      constriction, then collapse happens at severity of 75% and above. The former
      assumption is based on the requirement of adequate blood supply to the downstream
      organs/tissue, while the latter stems from the fact that the pumping mechanism of
      the body has a limited capacity in regulating blood pressure, in case a stenosis
      appears in the vasculature.

PMID- 19591049
TI  - A novel method for indirectly monitoring arterial pO(2) during cardiopulmonary
      bypass.
AB  - Arterial blood oxygen tension (P(a)O(2)) is a vital variable that has to be
      monitored during cardiopulmonary bypass (CPB). The aim of this study was to
      develop an alternative method for continuously P(a)O(2) monitoring during CPB,
      based on measurements of exhaust-gas from an oxygenator. A total of 15 adult
      patients undergoing CPB (n = 81 samples) were included in a study in order to
      develop an appropriate algorithm for P(a)O(2) estimation based on exhaust gas
      monitoring of the oxygen tension (P(ex)O(2)). The acquired data was used as a
      basis for developing a statistical prediction algorithm designed for continuously
      estimating the P(a)O(2)-level based on exhaust gas data in combination with data
      from the surrounding medical equipment. A new instrument was developed in order
      to implement this P(a)O(2) prediction algorithm and was tested on five patients
      (n = 39 samples). When the first sample was used for calibrating the instrument,
      the mean (SD) error was 8.7% (7.3%) with a 95% CI of 6.1-11.3%. Our results
      indicate that a pO(2)-exhaust monitoring device with adequate precision is
      obtainable, but further studies are required.

PMID- 19591050
TI  - A new method to measure heart rate with EMFi and PVDF materials.
AB  - In this paper we propose a new simple method to measure the heart rate of a
      person sitting on a chair or lying in a bed. The heart rate is measured with a
      thin sensor pad consisting of separate electromechanical film (EMFi) and
      polyvinylidenefluoride (PVDF) transducers located beneath the leg of chair or
      bed. This study aims to evaluate the operation of the sensor system with
      measurements, and also to compare the results provided by the two transducer
      materials. Based on the results obtained here, the heart rates measured with the
      transducers mainly corresponded to the values of reference ECG signal. Some minor
      differences between the heart rate values of PVDF and EMFi appeared, especially
      in supine position, possible due to the material sensitivities to different force
      directions. However, to conclude, both materials seem to be convenient for this
      kind of measurement of heart rate.

PMID- 19591051
TI  - Phase change material for thermotherapy of Buruli ulcer: modelling as an aid to
      implementation.
AB  - A mathematical model was developed and validated to predict the thermal behaviour
      of a heat application device based on a phase change material (pcm) for the heat
      treatment of Mycobacterium ulcerans infection (Buruli ulcer). The thermal model
      allows the prediction of skin surface temperatures and an optimization of the
      amount of pcm with respect to discharge time. A first prototype of such a pcm
      bandage was manufactured and used in a proof-of-principal trial in Cameroon. The
      experimental data were analysed and yielded no difference in thermoregulatory
      response between people living in hot or moderate climate. Short-term maximum
      skin surface temperatures of 42 degrees C are tolerable; the pcm bandage keeps
      the skin surface temperature above 40 degrees C for about four to five hours.
      This makes such pcm bandages an ideal device for the heat treatment of Buruli
      ulcer. The pcm bandage is easy to apply, cheap, and thus is well suited for use
      in low-resource countries.

PMID- 19591052
TI  - Prenatal fear of childbirth and anxiety sensitivity.
AB  - OBJECTIVE: Fear of childbirth (FOC) or what is historically referred to as
      tokophobia (a phobic state where a woman avoids childbirth despite desperately
      wanting a baby), is known to complicate the delivery process. In this study, the
      relationship of Anxiety Sensitivity (AS) to FOC was examined given that AS is a
      risk factor for other fears. Specifically, the contribution of three AS
      dimensions (physical, psychological or social concerns) relative to other factors
      (e.g., parity of the mother, trait anxiety) in accounting for FOC was explored.
      METHODS: Women in their final 4 months of pregnancy (n = 110) completed the
      Anxiety Sensitivity Index, the State-Trait Anxiety Inventory-Trait Scale and the
      Wijma Delivery Expectancy/Experience Questionnaire. RESULTS: Most demographic
      variables were non-significant in predicting FOC with the exception of
      participants' parity. Multiple regression analysis revealed that AS-physical
      concerns significantly predicted elevated FOC even after controlling for parity
      and trait anxiety; higher levels of AS-physical concerns, higher trait anxiety,
      and expecting a first child all independently predicted greater FOC. CONCLUSION:
      Variance in FOC is explained, in part, by AS-physical concerns. Further, AS
      physical concerns are distinct from trait anxiety in predicting FOC. Similar to
      other fears, the results support the possibility that AS may be a risk factor for
      elevated FOC.

PMID- 19591053
TI  - Attitudes toward menstrual suppression and conformity to feminine norms in young
      and middle-aged Mexican women.
AB  - Seventy seven college students and 66 middle-aged Mexican women completed an
      adapted questionnaire of attitudes toward menstrual suppression and the
      Conformity to Feminine Norms Inventory. Participants showed a great interest in
      menstrual suppression, but few were familiar with this issue. Young women would
      like to have longer menstrual cycles than monthly and were more supportive of
      menstrual suppression than middle-aged women. Women who would prefer to have
      longer menstrual cycles showed less conformity to feminine norms. These findings
      are discussed in light of differences between age cohorts, and the relationship
      between the studied variables and attitudes toward menstruation.

PMID- 19591054
TI  - Survey of Japanese infertile couples' attitudes toward surrogacy.
AB  - AIM: To clarify Japanese infertile couples' attitudes toward surrogacy, and
      analyse the results according to the contextual factors: ethical, social and
      medical aspects. METHODS: We performed a questionnaire survey anonymously on the
      attitude toward gestational surrogacy and traditional surrogacy in Japanese
      infertile couples (103 women and 60 men) between June and August 2000. We
      examined the relation between the acceptability of surrogacy and the background
      factors (age, type of procedure, the number of clinics visited, etc.), and also
      analysed the woman required as each type of surrogate mother whether the presence
      or absence of siblings in any of the infertile couple. RESULTS: The rates of
      using gestational and traditional surrogacy if they were necessary were 17% and
      7% of women, 23% and 8% of men, respectively. ART group, > or =35 years of age
      group and < or =2 clinics visited group as a contextual factor influenced their
      affirmative determinants. Approximately 70% of the infertile couples preferred
      anonymity as a surrogate gestational mother. Regardless of whether each partner
      had a full sister, these tendencies were observed. CONCLUSIONS: We found the
      contextual factors related to the acceptability of surrogacy. The ongoing
      deliberations toward surrogacy considering certain conditions of a concerned
      couple would be highly desirable.

PMID- 19591056
TI  - Feasibility of opto-electronic surgical instrument identification.
AB  - One essential precondition of workflow analysis in minimally invasive surgery is
      a continuous data inflow in real time, in particular on the instruments in use.
      However, reliable identification systems are missing to date. We developed an
      automatic identification system which detects and registers the individual
      instrument during insertion into the trocar. The system is based on an opto
      electronic object detection system using barcode 2/5 interleaved (printed out vs.
      lasered) which is detected by a micro endoscopic camera and light device.
      Evaluation was performed in vitro (laparoscopic training simulator) and in vivo
      (animal experiment) on 5 mm and 10 mm instruments with different insertion
      velocities into the trocar (20/10/1 cm/sec.). Furthermore, registration accuracy
      with a 1 - 5 sec. barcode retention period was evaluated. The best results were
      achieved with a 5 sec. static retention period of the barcode in the camera focus
      with a printed barcode. Retention periods of less than 5 sec. and dynamic
      insertions led to a significant decline of the detection rate. Opto-electronic
      barcode registration could be a promising technology for an automatic instrument
      registration. Although not yet mature for clinical application, the introduced
      system showed reliable results under static conditions.

PMID- 19591057
TI  - Binge drinking and unsafe sex: a study of narcology hospital patients from St.
      Petersburg, Russia.
AB  - The purpose of this study was to assess the association between binge alcohol use
      and unprotected sex in Russian substance users. Participants (N = 181) were
      narcology hospital patients assessed on demographics, alcohol use, risky sex, and
      sexually transmitted disease/human immunodeficiency virus (STD/HIV) diagnoses.
      Adjusted generalized estimating equations (GEEs) logistic regression analysis
      examined the association between binge drinking and same-day unprotected sex
      across each of the past 30 days, per participant (N = 5430 observations).
      Participants were age 18 to 55 years, 75% male, and 64% binge drinking. Sex trade
      was reported by 27%; history of STDs by 43%; and HIV by 15%. One fourth of daily
      observations included sex; 88% of these involved unprotected sex. Binge drinking
      was not associated with same-day unprotected sex (adjusted odds ratio [OR(adj)] =
      1.0, 95% confidence interval [CI] = 0.7-1.4, chi(2)(1, N = 5219) = 0.01, ns).
      Findings document substantial HIV/STD risk and prevalence among Russian narcology
      patients, but no link between binge drinking and unprotected sex in this
      population, possibly due to very low rates of condom use generally.

PMID- 19591058
TI  - Project integrate: translating screening and brief interventions for alcohol
      problems to a community hospital emergency department.
AB  - Screening and brief intervention (SBI) for alcohol problems in the emergency
      department (ED) is effective. The objective of this study was to examine the
      translation of SBI into a busy community ED environment. The authors assessed key
      stakeholders views of SBI delivery model, then utilized feedback to adapt model.
      Adoption of SBI was recorded, with data collected on use of screening tool, and
      referral for a BI. Model was modified due to physicians' and nursing resistance;
      physicians only screened and a research assistant (RA) delivered the BI. When the
      RA was present, screening by ED staff increased from 50% to 71% but returned to
      50% after the RA left. An identified opportunity was increased nursing interest
      after observation of SBI, with 15 nurses trained in SBI after ED intervention
      concluded. Important barriers to translating SBI to community ED clinical
      practice exist. However, with additional staff present, high levels of SBI can
      occur.

PMID- 19591059
TI  - Survey of alcohol and other drug use attitudes and behaviors in nursing students.
AB  - Statewide nursing student alcohol and other drug (AOD) use attitudes and
      behaviors were assessed. Response was 929/2017 (46%) (practical nursing [n =
      173/301] 57.3%; diploma and associate degree in nursing [n = 282/417] 67.6%;
      bachelor of science in nursing [n = 474/1299] 36.5%). Nearly 44% reported
      inadequate substance abuse education. Past-year AOD use included tobacco 36.9%,
      marijuana 6.8%, sedatives 4.6%, and opioids 2.6%. Past-year AOD-related events
      included blackouts 19.8%, class/work under the influence 6.3%, patient care under
      the influence 3.9%, lowered grades/job evaluations 6.6%, and legal charges 3.6%.
      Heavy drinking was reported by 28.9%. Practical nursing (PN) students most often
      reported tobacco use and sedative use, whereas Bachelor of Science in nursing
      (BSN) students most often reported marijuana use. Family histories of alcohol
      related problems and drug-related problems were reported, respectively, by 48.1%
      and 19.2% of respondents; 51.1% reported at least one of these. PN students most
      often reported such family histories. Nursing educational systems should
      proactively address student AOD prevention, education, and assistance.

PMID- 19591060
TI  - Implementing evidence-based practices in community treatment programs: initial
      feasibility of a counselor "toolkit".
AB  - Community substance abuse treatment programs face many barriers to adopting
      "evidence-based" therapies. Training budgets are inadequate to permit acquisition
      of complex skills, there is little clinical supervision available, and almost all
      counseling is done in group sessions. The authors adopted an approach widely used
      in the teaching field-developing a resource "toolkit" for a specific topic, in
      this case, a Decisional Balance exercise often used in the evidence-based
      treatment approach of Motivational Interviewing. This trial toolkit was comprised
      of a DVD (televised during group to illustrate the clinical concept), a laminated
      counselor guide (to provide guidance and talking points for the counselor during
      group), and some worksheets and wallet cards for patients to retain key points
      (see Table 1). A feasibility trial assessed the acceptability, and sustainability
      of the "Decisional Balance" concept toolkit among 26 counselors and 210 of their
      patients, from 6 community-based substance abuse treatment programs. The great
      majority of patients (97%) and all counselors (100%) reported they were satisfied
      with the toolkit session; 84% of patients said they would like more groups like
      the toolkit session. Almost all counselors (96%) were still using at least one
      component of the toolkit 3 months after their initial exposure with no prompting.
      The toolkit curriculum-based approach may be a viable and attractive way of
      translating core concepts from sophisticated evidence-based therapies into use by
      counselors within contemporary, community-based treatment programs with minimal
      training.

PMID- 19591061
TI  - Motivational enhancement therapy to increase resident physician engagement in
      substance abuse education.
AB  - Rates of screening, brief intervention, and referral to treatment (SBIRT) for
      alcohol and drug use by physicians remain low, despite evidence of efficacy.
      Motivational enhancement therapy (MET) may be a promising means to help
      physicians resolve ambivalence about intervening with alcohol and drug users and
      take advantage of educational opportunities. In the present study, 9 internal
      medicine residents received brief MET prior to standard education in SBIRT.
      Residents' self-reported SBIRT attitudes and behaviors were measured before the
      intervention and at a 5-week follow-up point. Changes in SBIRT attitudes and
      behaviors all occurred in the expected direction, although, due to the small
      sample size, none reached statistical significance. Results suggest that MET may
      enhance educational opportunities and lead to changes in SBIRT behavior.

PMID- 19591062
TI  - Legal ages for purchase and consumption of alcohol and heavy drinking among
      college students in Canada, Europe, and the United States.
AB  - Heavy drinking and associated negative consequences remain a serious problem
      among college students. In a secondary analysis of data from two published study,
      the authors examine the correlation between minimum legal age to purchase and/or
      consume alcohol and rates of heavy drinking among college students in 22
      countries. The published studies use identical definitions of heavy drinking and
      similar methodologies. In the study of 20 European countries and the United
      States, there is a positive correlation between prevalence of heavy drinking and
      both minimum legal purchase age (r =.34) and minimum legal drinking age (r =.19);
      in the study of Canada and the United States, there is a perfect positive
      correlation (r = 1.0). Examination of this evidence does not support the
      conclusion that a lower minimum legal age for purchase and/or consumption of
      alcoholic beverages is a protective factor for decreasing heavy drinking among
      college students.

PMID- 19591063
TI  - The interface between substance abuse and chronic pain management in primary
      care: a curriculum for medical residents.
AB  - OBJECTIVES: To develop and assess a housestaff curriculum on opioid and other
      substance abuse among patients with chronic noncancer pain (CNCP). METHODS: The
      two-hour, case-based curriculum delivered to small groups of medical housestaff
      sought to improve assessment and management of opioid-treated CNCP patients,
      including those with a substance use disorder. A two-page pre-post survey was
      administered to assess self-efficacy change on a scale from 1 (strongly disagree)
      to 5 (strongly agree). RESULTS: Of 47/50 (94%) respondents, self-efficacy
      significantly improved across all items (mean pre vs. post ratings, P <.001).
      Housestaff were more prepared to manage patients on chronic opioid medication
      (2.8 vs. 3.8), including those with substance use disorders (2.3 vs. 3.4). They
      felt more prepared to identify opioid dependence (2.8 vs. 3.9) and overall rated
      the curriculum favorably (4.2). CONCLUSIONS: The brief curriculum was well
      received and appears effective. Further study is needed to determine practice
      impact.

PMID- 19591064
TI  - Inquiries about and initiation of buprenorphine treatment in an inner-city
      clinic.
AB  - Despite increases in opioid dependence, availability of buprenorphine treatment
      remains limited. Reasons may include health center concerns about becoming
      overwhelmed or attracting patients who differ from the local community. This
      study documents inquiries about and initiation of buprenorphine treatment in an
      inner-city health center. From 2006-2008, we collected demographic information
      and subsequent treatment data for everyone who inquired about treatment. Of the
      324 people who inquired, 55.6% initiated treatment. The number of inquiries
      increased gradually over time, and most came from local community residents
      (80.4%). These results may allay health center concerns, and can help planning
      for buprenorphine treatment.

PMID- 19591065
TI  - Time-dependent neuroendocrine alterations and drug craving during the first month
      of abstinence in heroin addicts.
AB  - RATIONALE: Heroin use and withdrawal cause abnormality in the endocrine system.
      However, the time course of neuroendocrine alterations in heroin addicts during
      pharmacologically unassisted withdrawal is still unclear. OBJECTIVES: To
      investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta
      endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of
      abstinence in heroin addicts. METHODS: Twelve heroin addicts and eight matched
      healthy control subjects were recruited for this study. The neuroendocrine
      alterations and self-reported heroin craving, anxiety, and depression in heroin
      addicts were assessed at different time points (days 3, 10, and 30) of first
      month of abstinence from heroin use. RESULTS: Self-reported heroin craving,
      anxiety, and depression in heroin addicts decreased gradually during the first
      month of abstinence. The cortisol levels increased from abstinence day 3 to 30,
      while ACTH and beta-EP levels decreased over this period in heroin addicts. The
      leptin and NPY levels were significantly decreased on days 3 and 10 but had
      normalized on day 30 of abstinence. A positive correlation between cortisol level
      and heroin craving, anxiety, and depression was observed, while a negative
      correlation was observed between beta-EP level and craving and anxiety and
      between leptin and depression and NPY and anxiety. CONCLUSIONS: Abnormal
      alterations in the neuroendocrine system, including levels of cortisol, ACTH and
      beta-EP persist throughout the first month of abstinence. These results suggest
      that neuroendocrine system dysfunctions in heroin abusers is independent of the
      acute and protracted withdrawal syndromes, and may thus contribute to relapse to
      heroin use.

PMID- 19591066
TI  - Differences in sexual risk behaviors among male and female HIV-seronegative
      heterosexual methamphetamine users.
AB  - BACKGROUND: Despite increased awareness and attention towards methamphetamine
      (MA) use among men who have sex with men (MSM), few studies have examined
      behaviors and effects of MA use among heterosexual populations. OBJECTIVE: To
      learn whether behaviors and effects of MA use among heterosexuals differ
      according to gender. METHODS: We examined gender differences in sociodemographic
      characteristics, drug use practices, sexual behaviors, and consequences and
      motivations for MA use among 452 HIV-negative MA users (306 men, 146 women) who
      had engaged in unprotected sex and used MA in the previous two months. RESULTS:
      Females in the sample were younger and more likely to be married, to have been
      diagnosed with an STI in the last two months, and to report having been
      introduced to MA by a sexual partner. Women were also more likely to experience
      depressive symptoms and to report using MA "to lose weight." Men were more likely
      to engage in sex marathons while high on MA and to use MA "to enhance sexual
      pleasure." CONCLUSION: These differences suggest the importance of crafting
      gender-specific intervention messages, and they may contribute to identifying
      individuals at risk for initiating MA use. SCIENTIFIC SIGNIFICANCE: Our findings
      contribute to our knowledge of gender differences in behaviors and effects of MA
      use among heterosexuals. Future studies would benefit from collection of
      longitudinal data (to assess causal relationships) and use of a control group (to
      distinguish correlates of MA use from those of drug use in general).

PMID- 19591067
TI  - Patient and provider attitudes towards monitored naltrexone treatment of alcohol
      dependence in schizophrenia.
AB  - OBJECTIVE: To describe the attitudes of patients and their mental health
      providers regarding participation in a controlled trial of directly monitored
      naltrexone (NTX) treatment for alcohol dependence in schizophrenia. METHOD:
      Ninety participants with schizophrenia and their providers were asked to report
      opinions of treatment with oral NTX or placebo 3 times per week for 12 weeks,
      motivational counseling (MI), and voucher-based incentives (VBI) for attendance.
      RESULTS: Seventy-nine percent of participants "liked the study a lot," and 94%
      reported that it was helpful. Study components rated as helpful by participants
      were: VBI (95% of participants), meeting with staff 3 times per week (84%),
      reporting alcohol use (82%), MI (82%), reporting psychiatric symptoms (73%),
      breath alcohol testing (72%), and study medication (57%). Benefits reported by
      patients were: feeling better mentally (67%), drinking less (52%), feeling better
      physically (49%), and stopping drinking (27%). Seventy percent of providers
      reported that the study was helpful. Benefits noted by providers included:
      reduced drinking (33%), better treatment adherence (32%), stopping drinking
      (23%), and reduced psychiatric symptoms (22%). Patient/provider responses agreed
      on helpfulness with stopping or reducing drinking. CONCLUSIONS: Most participants
      with schizophrenia liked participating in a clinical trial of directly observed
      naltrexone treatment for alcohol dependence, and found incentives for attendance,
      frequent staff contact and monitoring of drinking, and motivational counseling to
      be the most helpful. Most participants reported improvement in mental health and
      reduced drinking. Mental health providers also reported that the study was
      helpful, but they did not describe the same degree of benefit as did patients.

PMID- 19591069
TI  - Successful pregnancy outcome in Ehlers-Danlos syndrome, vascular type.
AB  - BACKGROUND: Ehlers-Danlos syndrome (EDS) is a rare connective tissue disorder
      characterized by tissue fragility, translucent skin and joint hypermobility.
      Patients with the vascular type of EDS are prone to spontaneous arterial and
      visceral rupture. Pregnancy for women with vascular EDS can be life-threatening.
      Mortality rates are high due to the increased risk for uterine and arterial
      rupture in the peripartum period. CASE: We describe the counseling,
      multidisciplinary management, protocol, and successful pregnancy outcome of a 32
      year-old woman with vascular EDS. CONCLUSION: There is no consensus in the
      literature on the timing and mode of delivery for pregnant women with vascular
      EDS. The management undertaken in our patient may assist others in optimizing the
      perinatal outcome in other women who elect to continue their pregnancy despite
      the risks of this severe medical condition.

PMID- 19591071
TI  - Maternal anti-protein Z antibodies in pregnancies complicated by pre-eclampsia,
      SGA and fetal death.
AB  - OBJECTIVE: Low maternal plasma protein Z (PZ) concentrations were reported in
      patients with pre-eclampsia (PE), a small for gestational age (SGA) neonate, and
      a fetal demise (FD). Anti-protein Z antibodies (APZ-AB) have been proposed as a
      possible underlying mechanism leading to low plasma PZ concentrations. The
      objective of this study was to determine the maternal plasma concentration of APZ
      AB in women with a normal pregnancy, and patients with PE, an SGA neonate or a
      FD. STUDY DESIGN: A cross-sectional study included women in the following groups:
      (1) non-pregnant women (n = 45); and pregnant women with: (2) normal pregnancies
      (n = 70); (3) PE (n = 123); (4) SGA neonates (n = 51); and (5) a FD (n = 51).
      Plasma concentrations of anti-protein Z IgM and IgG antibodies were measured by
      ELISA. Elevated APZ-AB was defined as >75th, 90th and 95th percentile of the
      normal pregnancy group. Non-parametric statistics were used for analyses.
      RESULTS: (1) Patients with an SGA neonate had a higher median maternal plasma IgG
      APZ-AB concentration than women with normal pregnancies (p < 0.001), and patients
      with PE (p < 0.001) or with a FD (p = 0.001). (2) The proportion of patients with
      a maternal plasma IgM APZ-AB concentration >90th percentile was higher in the SGA
      group than in the PE group (p = 0.01). (3) Patients with PE maternal plasma IgM
      APZ-AB concentration >90th percentile had a higher rate of villous thrombosis (p
      = 0.03) and persistent muscularization of basal plate arteries (p = 0.01) than
      those with IgM APZ-AB concentration <90th percentile; and (5) Patients with FD
      and maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate
      of umbilical phlebitis and arteritis than those with IgM APZ-AB concentration
      <90th percentile (p = 0.003). CONCLUSIONS: (1) Patients with SGA neonates have a
      higher median plasma concentration of IgG APZ-AB than normal pregnant women, or
      patients with PE or FD; and (2) maternal plasma IgM APZ-AB concentration >90th
      percentile was associated with vascular placental lesions in patients with PE,
      but not in those with an SGA neonate, suggesting that in a subset of patients,
      these antibodies can be associated with abnormal placentation and pregnancy
      complications.

PMID- 19591072
TI  - Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and
      preterm, and intra-amniotic infection/inflammation.
AB  - OBJECTIVE: Intra-amniotic infection/inflammation (IAI) is one of the most
      important mechanisms of disease in preterm birth. Triggering receptor expressed
      on myeloid cells (TREM)- 1 is a transmembrane glycoprotein expressed by
      neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in
      biological fluids and tissues infected by Gram (+) and Gram (-) bacteria and
      fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and
      its soluble form (sTREM-1) is released in the presence of infection. The aim of
      this study was to determine the effect of gestational age, parturition (term and
      preterm) and IAI in the amniotic fluid (AF) concentrations of sTREM-1. STUDY
      DESIGN: This cross-sectional study included 434 patients in the following groups:
      (1) mid-trimester of pregnancy (14-18 weeks, n = 38); (2) normal pregnant women
      at term with (n = 39) and without (n = 39) labor; (3) patients with spontaneous
      preterm labor (PTL) and intact membranes classified into: (a) PTL who delivered
      at term (n = 99); (b) PTL who delivered preterm (<37 weeks gestation) without IAI
      (n = 80); and (c) PTL with IAI (n = 59); and (4) women with preterm prelabor
      rupture of membranes (PROM) with (n = 40) and without (n = 40) IAI. The AF
      concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non
      parametric statistics were used for analyses. RESULTS: (1) sTREM-1 was detected
      in all the AF samples; (2) the median AF sTREM-1 concentration at term was higher
      than in the mid-trimester (4277.6 pg/ml vs. 1140.4 pg/ml; p < 0.001); (3) among
      patients with PTL, the median AF sTREM-1 concentration was higher in patients
      with IAI than in those without IAI (6154.4 pg/ml vs. 3282.8 pg/ml; p < 0.001) and
      those with PTL who delivered at term (6154.4 pg/ml vs. 2794 pg/ml; p < 0.001);
      (4) patients with preterm PROM with IAI had a higher median AF sTREM-1
      concentration than those without IAI (7893.1 pg/ml vs. 3386.6 pg/ml; p < 0.001);
      (5) no differences were observed in the median AF sTREM-1 concentration between
      patients with spontaneous labor at term and those at term not in labor (4712.4
      pg/ml vs. 4277.6 pg/ml; respectively p = 0.4); and 6) an AF sTREM-1 concentration
      >or=6416 pg/ml (derived from a ROC curve) had a sensitivity of 72% and a
      specificity of 89% for the diagnosis of intra-amniotic infection. CONCLUSIONS:
      sTREM-1 is a physiologic constituent of the AF, and its concentration: (1) is
      significantly elevated in the presence of IAI; (2) increases with advancing
      gestation; and (3) does not change in the presence of spontaneous labor at term.
      We propose that sTREM-1 play a role in the innate immune response against intra
      amniotic infection.

PMID- 19591077
TI  - Masked priming effect reflects evidence accumulated by the prime.
AB  - In the same-different match task, masked priming is observed with the same
      responses but not different responses. Norris and Kinoshita's (2008) Bayesian
      reader account of masked priming explains this pattern based on the same
      principle as that explaining the absence of priming for nonwords in the lexical
      decision task. The pattern of priming follows from the way the model makes
      optimal decisions in the two tasks; priming does not depend on first activating
      the prime and then the target. An alternative explanation is in terms of a bias
      towards responding "same" that exactly counters the facilitatory effect of
      lexical access. The present study tested these two views by varying both the
      degree to which the prime predicts the response and the visibility of the prime.
      Unmasked primes produced effects expected from the view that priming is
      influenced by the degree to which the prime predicts the response. In contrast,
      with masked primes, the size of priming for the same response was completely
      unaffected by predictability. These results rule out response bias as an
      explanation of the absence of masked priming for different responses and, in
      turn, indicate that masked priming is not a consequence of automatic lexical
      access of the prime.

PMID- 19591078
TI  - Task switching and subjective duration.
AB  - Three experiments investigated the effects of switching from a nontiming task
      (addition of rapidly presented digits) to estimation of the duration of short
      tones or visual stimuli (Experiments 1 and 2), or the production of time
      intervals (Experiment 3). In general, compared with trials without a task-switch,
      trials involving a switch resulted in shorter duration estimates, but longer
      productions. The difficulty of the nontiming task, and the gap between the
      nontiming task and the timing task, also played a role, at least in some cases.
      Verbal estimates were shortened more at longer stimulus durations than at shorter
      ones in both experiments using this method. In general, the task-switch procedure
      produced opposite effects to "speeding up the clock" manipulations. The data were
      discussed in terms of models involving internal clock switch processes, including
      the notions of an "attentional gate" or a "flickering switch".

PMID- 19591073
TI  - Adiponectin in amniotic fluid in normal pregnancy, spontaneous labor at term, and
      preterm labor: a novel association with intra-amniotic infection/inflammation.
AB  - OBJECTIVE: Adiponectin, an anti-inflammatory and anti-diabetogenic adipokine, has
      an important regulatory effect on both the innate and adaptive limbs of the
      immune response. The objective of this study was to determine whether adiponectin
      is present in amniotic fluid (AF) and if its concentration changes with
      gestational age, in the presence of labor, and in the presence of intra-amniotic
      infection (IAI) in patients with spontaneous preterm labor (PTL) and intact
      membranes. STUDY DESIGN: This cross-sectional study included 468 patients in the
      following groups: (1) women in the mid-trimester of pregnancy (14-18 weeks) who
      underwent amniocentesis for genetic indications and delivered a normal neonate at
      term (n = 52); (2) normal pregnant women at term with (n = 49) and without (n =
      41) spontaneous labor; (3) patients with an episode of PTL and intact membranes
      who were classified into: (a) PTL who delivered at term (n = 149); (b) PTL who
      delivered preterm (<37 weeks gestation) without IAI (n = 108); and (c) PTL with
      IAI (n = 69). Adiponectin concentration in AF was determined by ELISA. RESULTS:
      (1) The median AF adiponectin concentration at term was significantly higher than
      in the mid-trimester (35.6 ng/ml, interquartile range [IQR] 26.4-52.7 vs. 29.9
      ng/ml, IQR 19.9-35.2; p = 0.01); (2) among women with PTL and intact membranes,
      the median AF adiponectin concentration was significantly higher in patients with
      IAI than in those without IAI who delivered either at term (54.3 ng/ml, 39.0-91.8
      vs. 50.1 ng/ml, 33.2-72.8; p = 0.02) or preterm (47.6 ng/ml, 32.6-74.6; p =
      0.01); and (3) among women at term, there was no significant difference in the
      median AF adiponectin concentration between those with and without labor (33.7
      ng/ml, IQR 21.7-53.9 vs. 35.6 ng/ml, IQR 26.4-52.7; respectively p = 0.5).
      CONCLUSIONS: (1) Adiponectin is a physiologic constituent of AF; and (2)
      adiponectin concentrations in AF are increased significantly with advancing
      gestation and in the presence of IAI. Collectively, these findings suggest that
      adiponectin plays a dynamic role in normal gestation and in the presence of IAI.

PMID- 19591080
TI  - Understanding cumulative risk.
AB  - This paper summarizes the theory of simple cumulative risks-for example, the risk
      of food poisoning from the consumption of a series of portions of tainted food.
      Problems concerning such risks are extraordinarily difficult for naive
      individuals, and the paper explains the reasons for this difficulty. It describes
      how naive individuals usually attempt to estimate cumulative risks, and it
      outlines a computer program that models these methods. This account predicts that
      estimates can be improved if problems of cumulative risk are framed so that
      individuals can focus on the appropriate subset of cases. The paper reports two
      experiments that corroborated this prediction. They also showed that whether
      problems are stated in terms of frequencies (80 out of 100 people got food
      poisoning) or in terms of percentages (80% of people got food poisoning) did not
      reliably affect accuracy.

PMID- 19591079
TI  - Segmentation by lexical subtraction in Hungarian speakers of second-language
      English.
AB  - Using cross-modal form priming, we compared the use of stress and lexicality in
      the segmentation of spoken English by native English speakers (L1) and by native
      Hungarian speakers of second-language English (L2). For both language groups,
      lexicality was found to be an effective segmentation cue. That is, spoken
      disyllabic word fragments were stronger primes in a subsequent visual word
      recognition task when preceded by meaningful words than when preceded by
      nonwords: For example, the first two syllables of corridor were a more effective
      prime for visually presented corridor when heard in the phrase anythingcorri than
      in imoshingcorri. The stress pattern of the prime (strong-weak vs. weak-strong)
      did not affect the degree of priming. For L1 speakers, this supports previous
      findings about the preferential use of high-level segmentation strategies in
      clear speech. For L2 speakers, the lexical strategy was employed regardless of L2
      proficiency level and instead of exploiting the consistent stress pattern of
      their native language. This is clear evidence for the primacy and robustness of
      segmentation by lexical subtraction even in individuals whose lexical knowledge
      is limited.

PMID- 19591081
TI  - [Health effects of particulate matter exposure: current scientific knowledge].
AB  - INTRODUCTION: Air quality is not only important for respiratory health but it
      also influences the homeostasis of the whole human organism. In the past years
      numerous violations of European Union particulate matter thresholds have been
      recorded. METHODS: The present study is a selective literature analysis
      encompassing the epidemiology and pathophysiological effects of particulate
      matter. RESULTS: Epidemiological studies point to an association between chronic
      particulate matter exposure and mortality. The most prominent effects on the
      human body are present in subjects with cardiovascular or respiratory conditions.
      However, the effects of air pollutants need to be examined critically and the
      plausibility of thresholds should be evaluated in detail. DISCUSSION: The
      negative influences of chronic particulate matter exposure have been proven by a
      multitude of epidemiological and experimental studies. From the viewpoint of
      primary prevention, air quality plays a crucial role. This encompasses both the
      outdoor compartment with particulate matter and other pollutants and the indoor
      compartment with tobacco smoke.

PMID- 19591082
TI  - [Always out of breath? An analysis of a doctor's tasks in pneumology].
AB  - BACKGROUND: Currently, data from questionnaires have demonstrated increasing
      criticism from respiratory physicians regarding their working situation. They
      complain about long working hours, income and an increasing amount of time spent
      on documentation and administrative duties in particular. Since these criticisms
      are only subjective perceptions they should be compared to data that are more
      objective. Therefore, the aim of the current study was to collect precise data
      about physicians' work in respiratory medicine in order to analyse working
      routines. METHOD: The working days of 60 physicians in a respiratory medicine
      hospital ward were observed unobtrusively for a total of 565 hours. An
      ultramobile personal computer was used to record the type and duration of all job
      tasks. RESULTS: The study results illustrate that a physician's working day
      amounted to an average of 9 hours 15 minutes (SD = 0 : 46 : 59 h). Within this
      time span different time periods were spent on administrative tasks, internal
      communication and meetings as well as on communication with patients, ward rounds
      and medical examinations. CONCLUSION: This is the first real-time analysis of job
      tasks in respiratory medical care. Some of the problems with work schedules
      reported by the doctors themselves were partly verified. Regarding the study
      results, a reorganisation of job tasks coupled with medical assistance systems
      may prove useful in reducing the workload of respiratory physicians.

PMID- 19591083
TI  - [Nutritional status and body composition in COPD--what do we know?].

PMID- 19591084
TI  - [Treatment of respiratory papillomatosis--a case report on systemic treatment
      with bevacizumab].
AB  - BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a known but rare
      disease, caused by human papilloma virus and characterised by multiple exophytic
      lesions and uncontrolled growth of papilloma in the respiratory tract. The most
      common complication of RRP is stenosis of the trachea. Medical therapeutic
      options have so far been less effective. However, inhibition of vascular
      endothelial growth factor (VEGF) by bevacizumab does appear to be an effective
      treatment option for RRP. CASE REPORT: The case of a 32-year-old male patient
      with RRP who has been treated for his symptomatic tracheal stenosis four times a
      year since 1996 is described. Only treatment by laser ablation showed any
      efficacy. Alternative treatment options did not show any effect. In May 2006
      intrapulmonary lesions of RRP were also diagnosed but without any malignancy.
      From December 2007 to June 2008 the patient has been treated with bevacizumab. A
      visible regression of RRP and markedly less symptoms were observed. During this
      treatment no further laser ablation was necessary. CONCLUSION: Inhibition of VEGF
      by bevacizumab seems to offer a new and effective option in the medical
      management of RRP.

PMID- 19591085
TI  - [Characteristics of auto-CPAP devices during the simulation of sleep-related
      breathing flow patterns].
AB  - INTRODUCTION: The function of automatic CPAP devices is difficult to investigate
      using clinical examinations due to the high variability of breathing disorders.
      With a flow generator, however, identical breathing patterns can be reproduced so
      that comparative studies on the behaviour of pressure of APAP devices are
      possible. Because the algorithms of APAP devices based on the experience of users
      can be modified without much effort, also previously investigated devices should
      regularly be reviewed with regard to programme changes. QUESTIONS: Had changes
      occurred in the algorithms of 3 selected devices--compared to the previously
      published benchmark studies? Do the current versions of these investigated
      devices differentiate between open and closed apnoeas? METHOD: With a self
      developed respiratory pump, sleep-related breathing patterns and, with the help
      of a computerised valve, resistances of the upper respiratory tract were
      simulated. Three different auto-CPAP devices were subjected to a bench test with
      and without feedback (open/closed loop). RESULTS: Open loop: the 3 devices showed
      marked differences in the rate of pressure rise but did not differ from the
      earlier published results. From an initial pressure of 4 mbar the pressure
      increased to 10 mbar after a different number of apnoeas (1-6 repetitive
      apnoeas). Only one device differentiated between closed and open apnoeas. Closed
      loop: due to the pressure increase, the flow generator simulated reduced
      obstruction of the upper airways (apnoeas changed to hypopnoeas, hypopnoeas
      changed to flattening) but different patterns of pressure regulation could still
      be observed. CONCLUSION: By applying bench-testing, the algorithms of auto-CPAP
      devices can regularly be reviewed to detect changes in the software. The
      differentiation between open and closed apnoeas should be improved in several
      APAP devices.

PMID- 19591086
TI  - [Cheyne-Stokes respiration and cardiovascular risk].
AB  - Due to its high prevalence in patients with heart failure and its negative
      predictive value concerning morbidity and mortality, Cheyne-Stokes respiration
      (CSR) is a sleep disorders of major interest. CSR correlates with the degree of
      heart failure and is characterised by a typical crescendo/decrescendo breathing
      pattern combined with phases of central sleep apnoea, caused by pulmonary oedema
      and oscillation of ventilatory control. Thus, CSR is a marker of the severity of
      heart failure. Treatment of CSR first involves optimisation of heart failure
      therapy by cardiologists and then application of non-invasive means of
      ventilatory support. Treatment of patients with severe heart failure with non
      invasive positive pressure ventilatory support leads to a significant reduction
      of CSR, sympathetic activity, and daytime sleepiness and improves cardiac output
      and 6-minute walking distance. At present, a prospective randomised, controlled
      intervention-study (Serve-HF study) is being conducted in order to show if
      therapy of CSR can improve patient survival. This review describes the
      pathophysiology, epidemiology, and therapeutic options of CSR with a special
      focus on the elevated cardiovascular risk of patients with CSR.

PMID- 19591087
TI  - Meningitis as a presentation of macroprolactinoma.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea and consecutive meningitis are
      well recognised clinical features of macroprolactinomas invading the skull base
      and are mainly observed under a dopamine-agonist therapy regimen. To our
      knowledge, a clinical case of primary meningitis due to an untreated
      macroprolactinoma, without any history of rhinorrhea, has not been reported
      previously in the English literature. CASE REPORT: A 64-year-old patient
      presented with acute meningitis. He had no prior episode of CSF rhinorrhea.
      Neuroradiological imaging revealed a pituitary tumour with invasion and
      destruction of the skull base. Massive hyperprolactinaemia was proof of a
      prolactinoma. The patient underwent transsphenoidal adenomectomy. The skull base
      defect was sealed with a fascia lata graft. In the postoperative course, no
      further episode of meningitis and no CSF rhinorrhea occurred. The invasive
      residual tumour was successfully treated with cabergoline. CONCLUSION:
      Macroprolactinomas can present with meningitis without any prior history of CSF
      rhinorrhea. Surgical repair of the skull base defect is the treatment of choice
      in order to prevent further episodes of meningitis. Pituitary tumours should be
      considered as a cause of otherwise unexplained meningitis.

PMID- 19591088
TI  - Protective effect of sauchinone by upregulating heme oxygenase-1 via the P38 MAPK
      and Nrf2/ARE pathways in HepG2 cells.
AB  - Sauchinone, a unique lignan isolated from the roots of Saururus chinensis (Lour.)
      Baill. (Saururaceae), is reported to exert potent hepatoprotective, anti
      inflammatory actions and inhibitory effects on bone resorption. This study
      investigated the potency of sauchinone as a hepatic heme oxygenase (HO)-1 inducer
      and its protective effects in HepG2 cells. Treatment of the cells with sauchinone
      induced HO-1 expression and increased HO activity in a concentration- and time
      dependent manner. This expression conferred cytoprotection against oxidative
      injury induced by T-butyl hydroperoxide. HO-1 expression by sauchinone also
      suppressed T-butyl hydroperoxide-induced reactive oxygen species generation in
      HepG2 cells. Moreover, sauchinone promoted the nuclear accumulation of the
      nuclear factor, E2-related factor 2 (Nrf2), and increased the promoter property
      of the antioxidant response element (ARE). Furthermore, treatment of the cells
      with a p38 MAPK inhibitor (SB203580) reduced sauchine-induced HO-1 expression and
      its protective effects. These results suggest that sauchinone increases the
      cellular resistance of HepG2 cells to T-butyl hydroperoxide-induced oxidative
      injury, presumably through the p38 MAPK pathway-Nrf2/ARE-dependent HO-1
      expression.

PMID- 19591089
TI  - Three new vanilloid derivatives from the stems of Baccaurea ramiflora.
AB  - Three new (1-3) and four known (4-7) compounds were isolated from the stems of
      Baccaurea ramiflora. By analysis of 1D, 2D NMR, and MS data, the new compounds
      were identified as 4'-O-(6- O-vanilloyl)-beta-D-glucopyranosyl tachioside D (1),
      6'-O-vanilloylpicraquassioside D (2), and 6'-O-vanilloylicariside B(5) (3).
      Compound 1 exhibited significant DPPH radical-scavenging activity, with an IC(50)
      value of 36.9 microM, while compound 4 revealed weak antioxidant activity against
      H (2)O(2)-induced impairment in PC12 cells.

PMID- 19591090
TI  - Three new acylated glycosides from the stems of Casearia velutina and their
      protective effect against H2O2-induced impairment in PC12 cells.
AB  - Chemical investigation of the stems of Casearia velutina led to the isolation and
      structural elucidation of three new acylated glycosides, casearicosides A-C (1
      3), together with 13 known compounds. The structures of the new compounds were
      established by spectroscopic and chemical methods. These isolates were evaluated
      for protective effects against H(2)O(2)-induced impairment in PC12 cells and
      inhibitory activity against snake venom phosphodiesterase I. A brief
      chemotaxonomy of the genus Casearia is also discussed.

PMID- 19591091
TI  - Analysis of chemical constituents and taxonomic similarity of Salvia species in
      China using LC/MS.
AB  - Salvia species have an extensive distribution and a long history of medical use
      in China. In this study, chemical differences between different Salvia species
      were thoroughly investigated, and 86 constituents were characterized through a
      sensitive HPLC-DAD-ESI-MS (n) method. In total, 19 Salvia species were screened.
      Our study suggested that Ser. Brachylomae, Ser. Digitaloidites, Ser. Castaneae,
      and Ser. Miltiorrhizae were the sibling series (Ser. is short for series) and
      that Ser. Brachylomae, Ser. Maximowicziana, and Ser. Campanulatae were unique
      with regard to their constituents in addition to having componential affinity.
      This study offered a simple chemotaxonomy approach and a reasonable bioactivity
      interpretation of Salvia species.

PMID- 19591092
TI  - [Skin prick test with inhaled allergens in the general population of Lodz
      province].
AB  - INTRODUCTION: Skin prick tests are a common, fast and safe method used for atopy
      screening and identification of sensitizing allergens. The aim of this study was
      to evaluate the prevalence of the positive skin prick test (SPT) with common
      inhaled allergens in the general population of Lodz province and to identify the
      most common allergens. MATERIAL AND METHODS: A random sample of 1522 subjects
      aged from 3 to 80 was taken. Demographic data and medical histories were
      collected from all participants via standardized questionnaires. Skin prick tests
      were performed with ten aeroallergens. RESULTS: The complete data from 1340
      subjects (1057 adults and 283 children) were included for further analysis. At
      least one positive reaction to a tested aeroallergen was observed in 24.4% of
      studied subjects (24% of adults and 25.4% of children). Positive tests were
      observed most frequently in the group of patients with rhinitis. 12.2% of
      subjects showed a positive skin reaction without clinical symptoms of an allergic
      disease. The most common sensitizing allergens were house dust mites. No
      significant differences in sex and age between groups with positive SPT and
      negative SPT were observed in the study. Statistically significant differences
      between the studied regions (p = 0.037) were noticed in the case of the number of
      positive reactions and the kind of sensitizing allergen. CONCLUSIONS: The
      distribution of positive skin tests in the above study was similar to several
      epidemiological studies from central and eastern Europe. Skin prick tests are
      valuable epidemiological tools in the diagnosis of atopy and allergy.

PMID- 19591093
TI  - [Relationship between age and cardiovascular complications in obstructive sleep
      apnoea].
AB  - INTRODUCTION: Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular
      morbidity and mortality. The aim of this study was to assess relations between
      cardiovascular diseases (CVD) and age in OSA subjects. MATERIAL AND METHODS:
      Consecutive OSA subjects (AHI/RDI > 10, Epworth score > 9 points) were evaluated.
      The chest X-ray, spirometry, arterial blood gases, ECG, blood morphology and
      biochemistry were performed during trial treatment with autoCPAP. RESULTS: We
      studied 533 consecutive OSA patients, mean age 55.6 +/- 10.3 years (range 24-81),
      with obesity (BMI 34.4 +/- 6.6 kg/m(2)) and severe OSA (AHI/RDI 37.8 +/- 21.8).
      To evaluate relations between CVD and age, patients were divided into three
      groups. Group 1 < 50 years (123 subjects, 23.1%), Group 2 aged 50-60 years (250
      subjects, 46.9%) and Group 3 > 60 years (160 subjects, 30%). Subjects < 50 years
      were more obese and had higher AHI/RDI when compared to older groups. Incidence
      of arterial hypertension, coronary artery disease, atrial fibrillation, heart
      failure and stroke increased with age (higher in subjects > 60 years).
      CONCLUSIONS: Cardiovascular diseases were prevalent in OSA patients > 60 years.
      However the youngest group presented with more severe obesity and higher AHI/RDI.

PMID- 19591094
TI  - [Bronchial bacterial colonization in patients with lung cancer].
AB  - INTRODUCTION: Infections are a part of the natural course of lung cancer but few
      studies have looked at the clinical and microbiological documentation of
      infections in these patients. The aim of this study is to analyze the profile of
      potentially pathogenic bacteria that colonize the bronchial tree in patients with
      primary lung cancer. MATERIAL AND METHODS: The study was conducted from January
      2006 to August 2007. It included 44 consecutive patients (34 males and 10
      females) with primary lung cancer aged from 38 to 77 (mean age of 57.9 years). In
      all patients, bronchoalveolar lavage (BAL) was performed during
      bronchofiberoscopy. Obtained BAL fluid was subjected to microbiological
      examination. The number of bacteria present in 1 ml of fluid was estimated by
      quantitative culture. A diagnostic level was set on >or= 104 cfu/ml. RESULTS: In
      26 (59.1%) of 44 patients physiologic bacterial flora was found in the bronchial
      tree. In three cases (6.8%), potentially pathological bacteria were cultured but
      their number was < 104 cfu/ml. In 15 (34.1%) cases, the colonization of
      potentially pathogenic bacteria was >or= 104 cfu/ml. Both Gram-positive and Gram
      negative bacteria were isolated. The most frequently isolated bacterium in the
      first group was Streptococcus pneumoniae (n = 7), and in the second group
      Haemophilus influenzae (n = 3). Multibacterial colonization was found in five
      patients (11.4%). In four cases (9.1%), the bronchial tree was colonized
      simultaneously by two and in one case [2.3%] by three types of micro-organism.
      Multi-drug-resistant strains were not found in the examined materials but among
      Streptococcus pneumoniae the constitutive MLSB phenotype was observed.
      CONCLUSIONS: 1. Approximately 30% of patients with lung cancer had a respiratory
      tract colonized by micro-organisms whose number was higher than the assumed
      diagnostic level. 2. Among micro-organisms colonizing the lower respiratory
      tract, Gram-positive cocci such as Streptococcus pneumoniae and Staphylococcus
      aureus were dominant. 3. The analysis of antibiotic-resistance did not detect
      multi-drug-resistant micro-organisms but some strains of Streptococcus pneumoniae
      exhibited resistance to macrolide, lincosamide and streptogramin B.

PMID- 19591095
TI  - [Smoking habits in a family physician's practice].
AB  - INTRODUCTION: Poland is the one of the countries in the European Union with the
      highest prevalence of smokers. The involvement of family physicians in smoking
      cessation activity could improve this situation. The aim of this study was to
      estimate smoking habits, their intensity and nicotine dependence in a family
      physician's practice (urban and rural population). An additional aim was to
      estimate smoking habits in relation to the presence of smoking-related disease,
      gender, location and motivation to stop smoking. MATERIAL AND METHODS: This study
      was part of an investigation into the prevalence and severity of chronic
      obstructive pulmonary disease (COPD) in the same population. Statistical analysis
      of questionnaires about smoking and history of respiratory diseases, Fagerstrom's
      nicotine dependence test and a motivation to quit test were performed. RESULTS:
      Questionnaires were filled in by 1960 subjects (87% of those eligible). There
      were 29.6% current smokers, 24.9% ex-smokers, and 45.5% never-smokers. There were
      39.4% current smokers among men, and 23.3% among women. Current smokers were more
      numerous in the rural population. 54% of women urban dwellers and 73% of women
      from rural population never smoked. There were no significant differences in the
      motivation to stop smoking or in the nicotine dependence among smokers with and
      without COPD nor according to the severity of COPD. CONCLUSIONS: Smoking habits
      among the studied population were comparable with national and regional data. The
      intensity of smoking habits among female town dwellers is especially alarming.

PMID- 19591096
TI  - [Relationship between airway basement membrane thickness and lung function tests
      in patients with asthma].
AB  - INTRODUCTION: Airway remodeling is a characteristic feature of asthma. It is
      believed that airway remodeling affects lung function and bronchial hyper
      responsiveness. Therefore, the relationship between remodeling and lung function
      is still a matter of extensive research. However, the results of many studies are
      inconsistent. The aim of the study was to assess the relationship between lung
      function parameters and basement membrane (BM) thickness in patients with asthma.
      MATERIAL AND METHODS: Twenty asthma patients were chosen for the study (ten male,
      ten female, mean age 37 +/- 15 yrs). Ten were newly diagnosed, steroid-naive
      patients and the other ten were patients known to have asthma who had not been
      treated with steroids for at least three months. The study group was selected
      based on the results of: clinical assessment, allergic skin-prick tests, lung
      function testing and bronchial challenge with methacholine. Nine (45%) patients
      had chronic mild, nine (45%) had moderate and two (10%) had intermittent asthma.
      Mean FEV1% pred. was 83 +/- 18, mean FEV1%VC 69 +/- 9, mean FVC% pred. 101 +/-
      14. All patients underwent research fiberoptic bronchoscopy with BAL and
      bronchial mucosal biopsies. Light-microscopic measurements of BM thickness were
      performed in hematoxylin-eosin stained slides of bronchial wall specimens with
      semi-automatic software analysis MultiScan Base 08.98. RESULTS: Mean BM thickness
      was 12.8 +/- 2.8 microm (range: 8.5-20.7 microm). No significant correlations
      between BM thickness and FEV1% pred., FEV1%VC, FVC% pred., RV% pred., TLC% pred.,
      Raw (pre- and post-bronchodilator) and PC20 were observed. CONCLUSIONS: In our
      group of asthma patients, mean BM was significantly thickened. No relationship
      between BM thickness and lung function tests, including hyper-responsiveness, was
      found.

PMID- 19591097
TI  - [Methods of estimating concentration of the D-dimers used in venous
      thromboembolism diagnosis].
AB  - D-dimers (DD) are final products of stabilized fibrin degradation process.
      Elevated level of DD indicates parallel activation of both coagulation and
      fibrinolysis. D-dimers play important role in the diagnosis of deep vein
      thrombosis and pulmonary embolism. All diagnostic methods detecting DD are based
      on monoclonal antibodies. There are three basic techniques used to measure DD:
      latex agglutination, full blood agglutination and immunoenzymatic methods.
      Nowadays new methods based on in vivo detection of DD using antibodies labeled
      with technetium are under clinical evaluation.

PMID- 19591098
TI  - [D-dimer in diagnosis and treatment of pulmonary embolism].
AB  - D-dimer level estimation, specific fibrin degradation product, is a permanent
      part of diagnostic strategies of pulmonary embolism (PE). Approximately 30% of a
      suspected non-high risk PE can be ruled out with high sensitive D-dimer test when
      pre-test clinical probability is non-high. Recent guidelines underline that only
      very sensitive DD assays can be used. The main limitation of DD tests is
      relatively low specificity especially in hospitalized population, in elder
      patients, with cancer and in pregnancy. New indication for DD test mentioned in
      current guidelines is estimation of risk of recurrence after withdrawal of
      anticoagulant. Negative DD test identify patients with low risk of recurrence.

PMID- 19591099
TI  - [Multidrug resistance tuberculosis - current problems].
AB  - The rising occurrence of multidrug-resistant tuberculosis (MDR-TB), defined as
      resistance to at least isoniazid and rifampicin, is a serious worldwide problem.
      The treatment of MDR-TB with alternative chemotherapy is difficult due to side
      effects and treatment duration. It is also very expensive and sometimes
      unsuccessful. DOTS and DOTS-Plus strategy are necessary to achieve a good
      tuberculosis control.

PMID- 19591100
TI  - Chronic obstructive pulmonary disease and risk of infection.
AB  - This review article focuses on the risk of infections in patients with chronic
      obstructive pulmonary disease (COPD). Throughout the years there have been a
      number of studies describing the risk of pulmonary infections in patients with
      COPD, whereas only few studies have focused on the risk of infection outside the
      lungs. With increasing severity of COPD the risk of respiratory tract infection
      also increases. The impairment of the innate immune system is most likely
      responsible for both the colonization of respiratory tract with bacteria and for
      an increased risk of infection with new strains of bacteria causing acute
      exacerbations. Also lung infections like pneumonia, lung abscess and empyema are
      more often seen in patients with COPD than in healthy subjects. With regard to
      extrapulmonary infections, it seems that COPD patients are not at higher risk of
      infection compared with subjects without COPD. It is concluded that COPD is
      significantly associated with an increased risk of various respiratory tract
      infections, but not with infections outside the respiratory system.

PMID- 19591101
TI  - [Perspectives in gene therapy. Lecture in memory of Prof. Janina Misiewicz].

PMID- 19591102
TI  - [Smoking cessation in patients with chronic obstructive pulmonary disease].

PMID- 19591103
TI  - A history of pulmonary rehabilitation: back to the future.

PMID- 19591104
TI  - [Pharmacoeconomics of chronic obstructive pulmonary disease].

PMID- 19591105
TI  - BODE index: a new tool to stage and monitor progression of chronic obstructive
      pulmonary disease.

PMID- 19591106
TI  - Bridging the gap: the patient-doctor relationship.

PMID- 19591107
TI  - [Hemorrhagic parapneumonic effusion in a 64 year-old patient as the first symptom
      of hemophilia B].
AB  - Hemophilia B is an inherited, X chromosome-linked disease. It is usually
      diagnosed in childhood, sometimes in adolescence. The commonest symptoms include
      spontaneous or post-traumatic bleeding into the joints and/or muscles, as well as
      mucosal bleeding. Respiratory symptoms are rarely reported. We present the case
      of a 64 year-old man in whom bloody parapneumonic effusion (hemothorax) was the
      first symptom of hemophilia B. The reason for prolonged activated partial
      thromboplastin time (APTT) found on admission has not been elucidated. Since
      antibiotic therapy and pleural tube thoracostomy with intrapleural streptokinase
      were found to be ineffective, video-assisted thoracic surgery was performed with
      the right lung decortication. Post-operative treatment was complicated by massive
      pleural bleeding requiring two subsequent thoracotomies. Additional blood tests
      revealed factor IX deficiency and resulted in hemophilia B being diagnosed. The
      presented case proves that hereditary bleeding disorders may be diagnosed even in
      late adulthood. Intrapleural bleeding related to pneumonia and pleural
      inflammation might be the first presenting symptom. Hemophilia should be
      considered as a potential cause of APTT prolongation, even in an elderly patient
      with atypical presentation. Explaining the reason for APTT prolongation before
      the surgical procedure could have allowed to avoid severe bleeding in the
      described patient.

PMID- 19591109
TI  - [100 years of sanatorium in Rudka -- report of celebration of anniversary].

PMID- 19591108
TI  - [Langerhans cell sarcoma with pulmonary manifestation, mediastinum involvement
      and bronchoesophageal fistula. A rare location and difficulties in
      histopathological diagnosis].
AB  - Langerhans cell sarcoma, a neoplastic proliferation of Langerhans cells with
      malignant cytologic features, is a very rare disease. Only a few cases have been
      documented in the English-language literature. Special methods, like
      immunohistochemistry and/or ultrastructural examination, are indispensable for
      appropriate diagnosis. Correct diagnosis is difficult. In fact, the disease is
      often misdiagnosed. We present the case of a 47 year-old man with a large mass in
      the middle lobe of the lung, infiltrating anterior mediastinum, with multiple
      pulmonary round lesions and enlargement of local lymph nodes, and with
      bronchoesophageal fistula. Clinical examination indicated the possibility of
      advanced primary lung cancer. However, the first histological diagnosis was
      Langerhans cell histiocytosis. In spite of treatment, the progression of
      pulmonary lesions was observed. Therefore, upper- and middle-lobectomy was
      performed. The diagnosis of Langerhans histiocytosis was confirmed
      microscopically again. Nevertheless, the patient's condition deteriorated
      progressively and he was admitted to the National Tuberculosis and Lung Diseases
      Research Institute in order to establish a final diagnosis. Revision of earlier
      resected specimens, as well as an immunohistochemical and ultrastructural
      examination of samples, taken once again from a bronchial tumor, led to the
      establishment of a diagnosis of a unique form of Langerhans cell sarcoma with
      rare pulmonary manifestation.

PMID- 19591111
TI  - [Smoking and interstitial lung disease? Commentary to the article of E. Wiatr
      "smoking-related interstitial lung diseases"].

PMID- 19591113
TI  - [Commentary to the article of I. Kuprys-Lipinska et al. "Skin prick test with
      inhaled allergens in the general population of Lodz province"].

PMID- 19591115
TI  - Perspectives of primary care clinicians on teratogenic risk counseling.
AB  - BACKGROUND: Women of childbearing age are commonly prescribed medications by
      primary care providers (PCPs) that may cause birth defects if used during
      pregnancy. METHODS: To identify what PCPs perceive as barriers to and potential
      facilitators of providing counseling to women of childbearing age when
      teratogenic medications are prescribed, we conducted eight focus groups with 48
      PCPs recruited from four clinical settings in Pittsburgh, Pennsylvania. We
      explored PCPs' experiences counseling women about teratogenic medications. Each
      focus group was audio-recorded, transcribed, and coded using a grounded theory
      approach by three independent coders. RESULTS: PCPs feel responsible for
      counseling women when they prescribe medications that may cause birth defects,
      but note difficulties identifying clinically relevant sources of information on
      teratogenicity. Other barriers to providing counseling include limited visit
      times and lack of reimbursement for preconception or teratogenic risk counseling.
      PCPs find it challenging to identify patients who may become pregnant and who
      therefore need contraceptive and/or teratogenic risk counseling. PCPs expressed a
      desire for online resources that could be used when explaining medication risks
      to patients. PCPs feel that the development of patient information materials,
      electronic decision support tools, clinical care systems that routinely assess
      patients' pregnancy risk, and changes in the reimbursement structure may
      facilitate counseling patients about teratogenic risks. CONCLUSIONS: PCPs
      perceive themselves as playing an important role in providing their patients
      information on risk of medication-induced birth defects. To ensure safe
      prescription of teratogenic medications, PCPs suggest interventions at both the
      clinic and healthcare system levels.

PMID- 19591116
TI  - Maternal caffeine intake during pregnancy and orofacial clefts.
AB  - BACKGROUND: Moderate caffeine intake during pregnancy is common, but little is
      known about its potential association with birth defects. METHODS: The National
      Birth Defects Prevention Study is a population-based, case-control study of major
      birth defects, excluding infants with single-gene disorders and chromosomal
      abnormalities. This analysis includes infants with cleft lip with or without
      cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft
      was secondary to holoprosencephaly or amniotic band sequence. Mothers reported
      dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before
      pregnancy and reported intake of medications containing caffeine during
      pregnancy. We assessed the association between dietary caffeine intake, frequency
      of consuming each type of caffeinated beverage, medications containing caffeine,
      and CL/P or CPO among infants born from October 1997 through December 2004.
      RESULTS: This analysis included 1531 infants with CL/P, 813 infants with CPO, and
      5711 infants with no major birth defects (controls). Examining dietary sources
      among control mothers, 11% reported consuming at least 300 mg of caffeine per day
      and 17% reported consuming less than 10 mg of caffeine per day; high consumption
      (>or=3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas);
      medications containing at least 100 mg caffeine/dose were reported by less than
      1%. Although some effect estimates were elevated for moderate caffeine intake
      from all beverages, estimates were closer to the null for high caffeine levels.
      Isolated CL/P was associated with use of medications containing at least 100 mg
      of caffeine per dose. CONCLUSIONS: Our data do not suggest an association between
      maternal dietary caffeine intake and orofacial clefts, but caffeine-containing
      medications merit further study.

PMID- 19591118
TI  - When are summary ROC curves appropriate for diagnostic meta-analyses?
AB  - Diagnostic tests are increasingly evaluated with systematic reviews and this has
      lead to the recent developments of statistical methods to analyse such data. The
      most commonly used method is the summary receiver operating characteristic (SROC)
      curve, which can be fitted with a non-linear bivariate random-effects model. This
      paper focuses on the practical problems of interpreting and presenting data from
      such analyses. First, many meta-analyses may be underpowered to obtain reliable
      estimates of the SROC parameters. Second, the SROC model may be inappropriate. In
      these situations, a summary with two univariate meta-analyses of the true and
      false positive rates (TPRs and FPRs) may be more appropriate. We characterize the
      type of problems that can occur in fitting these models and present an algorithm
      to guide the analyst of such studies, with illustrations from analyses of
      published data. A set of R functions, freely available to perform these analyses,
      can be downloaded from (www.diagmeta.info).

PMID- 19591117
TI  - The correlated and shared gamma frailty model for bivariate current status data:
      an illustration for cross-sectional serological data.
AB  - Frailty models are often used to study the individual heterogeneity in
      multivariate survival analysis. Whereas the shared frailty model is widely
      applied, the correlated frailty model has gained attention because it elevates
      the restriction of unobserved factors to act similar within clusters. Estimating
      frailty models is not straightforward due to various types of censoring. In this
      paper, we study the behavior of the bivariate-correlated gamma frailty model for
      type I interval-censored data, better known as current status data. We show that
      applying a shared rather than a correlated frailty model to cross-sectionally
      collected serological data on hepatitis A and B leads to biased estimates for the
      baseline hazard and variance parameters.

PMID- 19591119
TI  - Development and validation of UPLC-MS/MS method for simultaneous determination of
      gestodene and ethinyl estradiol in rat plasma.
AB  - A selective and sensitive ultra-performance liquid chromatography method with
      tandem mass spectrometric detection for simultaneous determination of gestodene
      (GES) and ethinyl estradiol (EE) in rat plasma was developed and validated. GES,
      EE and the internal standard, norgestrel, were extracted with ethyl acetate,
      derivatized (EE only) with dansyl chloride and then back-extracted into diethyl
      ether-hexane (2:1, v/v). The separation was performed on an ACQUITY UPLC BEH
      C(18) column with gradient elution using mobile phase consisting of acetonitrile
      and water (both containing 0.1% formic acid). The detection was carried out by
      means of electrospray ionization (ESI) mass spectrometry in positive ion mode
      with multiple-reaction monitoring. Calibration curves of GES and EE were linear
      (r(2) >or= 0.99) over the concentration ranges 1.59-159 and 0.196-78.4 ng/mL,
      respectively. The intra- and inter-day precisions were not more than 6.9 and
      12.9% for GES and 10.6 and 9.0% for EE, and the accuracies were -2.5-8.0% for
      GES, and -7.2-0.19% for EE, respectively. The method herein described was
      superior to previous methods and was applicable to the pharmacokinetic study of
      GES and EE in rats.

PMID- 19591120
TI  - A simple and rapid method to assess lycopene in multiple layers of skin samples.
AB  - Topical application of lycopene is a convenient way to restore antioxidants
      depleted from the skin by UV radiation and achieve protection against premature
      aging and cancer. In this study, a simple, rapid and reproducible method to
      quantify lycopene in different skin layers was developed, validated and employed
      to assess this compound after skin penetration studies. Lycopene was extracted
      from the stratum corneum (SC) and viable epidermis and dermis (ED) by vortex
      homogenization and bath sonication in a mixture of acetonitrile and methanol
      (52:48, v/v). Lycopene was assayed by HPLC using a C(18) column, and
      acetonitrile:methanol (52:48, v/v) as mobile phase. The quantification limit of
      lycopene in samples of SC and ED was 35 ng/mL and the assay was linear from 35 to
      2000 ng/mL. Within-day and between-days assays coefficients of variation and
      relative errors (indicative of precision and accuracy) were less than 15% (or 20%
      for the limit of quantification). Lycopene recovery from SC and ED was dependent
      on the spiked concentration: for 50 ng/mL, recoveries were 88.3 and 90.5%; for
      100-1000 ng/mL, recoveries were 68.6-74.9%. This method has a potential
      application for lycopene quantification during formulation development and
      evaluation in the dermatological field.

PMID- 19591121
TI  - An analytical method for cyclosporine using liquid chromatography-mass
      spectrometry.
AB  - A liquid chromatographic mass spectrometric (LC-MS) assay has been developed for
      cyclosporine A (CyA) in rat plasma using amiodarone as internal standard (IS).
      Rat plasma (100 microL) containing drug and IS were extracted using liquid-liquid
      extraction with 4 mL of 95:5 ether:methanol. After evaporation of the organic
      layer the residue was reconstituted with 500 microL of water. Then the aqueous
      layer was transferred to LC-MS sample vials. A 10 microL volume was injected. The
      analysis was performed on a C(8) column 3.5 microm (2.1 x 50 mm) heated to 60
      degrees C with a mobile phase consisting of acetonitrile:methanol:0.2% NH(4)OH
      (60:20:20) at an isocratic flow-rate of 0.2 mL/min. The ions used for
      quantitation of CyA and IS were m/z 1202.8 and 645.9, with retention times of
      3.35 and 4.72 min, respectively. Linear relationships (r(2) > 0.99) were achieved
      between plasma or blood concentration and peak height ratios (drug:IS) over the
      concentration range 50-5000 ng/mL. The CV% and mean error were <19%. Based on
      validation data, the lower limit of quantification for the assay was 50 ng/mL.
      The reported assay method displayed high measures of linearity, sensitivity,
      reliability and precision, allowing its applicability in pharmacokinetic studies
      in rat.

PMID- 19591122
TI  - Ipriflavone pharmacokinetics in mutant Nagase analbuminemic rats.
AB  - Ipriflavone, a derivative of naturally occurring isoflavones, was primarily
      metabolized in rats via hepatic CYP1A1/2 and 2C11. Protein and mRNA expression of
      CYP1A2 in the liver, reported to be increased in mutant Nagase analbuminemic rats
      (NARs), should influence the pharmacokinetic parameters of ipriflavone. In this
      study, the contribution of hepatic CYP2C11 and intestinal CYP1A protein to the
      metabolism and the pharmacokinetic parameters of ipriflavone were examined after
      intravenous (20 mg/kg) and oral (200 mg/kg) administration to male Sprague-Dawley
      (control) rats and NARs. There was no change in the protein expression of hepatic
      CYP2C11. By contrast, CYP1A protein of the intestine increased by almost 100%.
      After the intravenous administration of ipriflavone to NARs, the Cl(nr) and AUC
      were unchanged, suggesting that the contribution of the increase in protein
      expression and mRNA level of hepatic CYP1A2 to hepatic metabolism of the drug in
      NARs seemed to be almost negligible. However, after the oral administration of
      ipriflavone to NARs, the AUC was significantly lower than that in the control
      rats (53.0% decrease), possibly due to the increased intestinal CYP1A that
      resulted in increased intestinal metabolism and decreased gastrointestinal
      absorption of ipriflavone in NARs.

PMID- 19591123
TI  - MicroRNA-122 might be a double-edged sword in hepatocellular carcinoma.

PMID- 19591124
TI  - Proteomics analysis of mitochondrial proteins reveals overexpression of a
      mitochondrial protein chaperon, prohibitin, in cells expressing hepatitis C virus
      core protein.
AB  - The hepatitis C virus (HCV) core protein is involved in viral pathogenesis such
      as oxidative stress induction and lipid metabolism disturbance, and is primarily
      located in the cytoplasm and endoplasmic reticulum in association with lipid
      droplets as well as in the mitochondria. To clarify the impact of the core
      protein on mitochondria, we analyzed the expression pattern of mitochondrial
      proteins in core protein-expressing cells by two-dimensional polyacrylamide gel
      electrophoresis. Several proteins related to the mitochondrial respiratory chain
      or protein chaperons were identified by mass spectrometry. Among the identified
      proteins with consistently different expressions, prohibitin, a mitochondrial
      protein chaperon, was up-regulated not only in core-expressing cells but also in
      full-genomic replicon cells and livers of core-gene transgenic mice. The
      stability of prohibitin was increased through interaction with the core protein.
      Further analysis demonstrated that interaction of prohibitin with mitochondrial
      DNA-encoded subunits of cytochrome c oxidase (COX) was disturbed by the core
      protein, resulting in a significant decrease in COX activity. CONCLUSION: The HCV
      core protein affects the steady-state levels of a subset of mitochondrial
      proteins including prohibitin, which may lead to an impaired function of the
      mitochondrial respiratory chain with the overproduction of oxidative stress.

PMID- 19591125
TI  - Variation in GRIN2B contributes to weak performance in verbal short-term memory
      in children with dyslexia.
AB  - A multi-marker haplotype within GRIN2B, a gene coding for a subunit of the
      ionotropic glutamate receptor, has recently been found to be associated with
      variation in human memory performance [de Quervain and Papassotiropoulos, 2006].
      The gene locus is located within a region that has been linked to a phonological
      memory phenotype in a recent genome scan in families with dyslexia [Brkanac et
      al., 2008]. These findings may indicate the involvement of GRIN2B in memory
      related aspects of human cognition. Memory performance is one of the cognitive
      functions observed to be disordered in dyslexia patients. We therefore
      investigated whether genetic variation in GRIN2B contributes to specific
      quantitative measures in a German dyslexia sample by genotyping 66 SNPs in its
      entire genomic region. We found supportive evidence that markers in intron 3 are
      associated with short-term memory in dyslexia, and were able to demonstrate that
      this effect is even stronger when only maternal transmission is considered. These
      results suggest that variation within GRIN2B may contribute to the genetic
      background of specific cognitive processes which are correlates of the dyslexia
      phenotype.

PMID- 19591126
TI  - Carotenoids with anti-Helicobacter pylori activity from Golden delicious apple.
AB  - Previously it was reported that hypophasic carotenoids of Golden delicious apple
      peel showed potent anti-H. pylori activity (MIC(50) = 36 microg/mL), comparable
      to metronidazole (MIC(50) = 45 microg/mL). To further investigate the involved
      active carotenoids of the apple peel extracts, seven carotenoids were isolated
      for the current study: (all-E)-luteoxanthin, (all-E)-neoxanthin, (9'Z)
      neoxanthin, (all-E)-antheraxanthin, (all-E)-violaxanthin, (9Z)-violaxanthin and
      (all-E)-lutein. The MIC(50) values of (all-E)-luteoxanthin, (all-E)-neoxanthin
      and (9'Z)-neoxanthin were 7.9, 11 and 27 microg/mL, respectively. Other
      carotenoids and beta,beta-carotene did not exhibit potent anti-H. pylori activity
      (MIC(50) > 100 microg/mL). An examination of structure and function suggested
      that active carotenoids contained a monofuranoid ring or an allenic bond in
      addition to an epoxy group and an additional two or three hydroxyl substituents
      on the side group.

PMID- 19591127
TI  - Editorial.

PMID- 19591128
TI  - Effect of hepatitis C virus and its treatment on survival.
AB  - The effect of hepatitis C virus (HCV) and its treatment on survival is not well
      defined. We undertook this study to determine the effect of HCV and its treatment
      on survival in a national cohort of HCV-infected veterans and uninfected
      controls. We used a national sample of HCV-infected persons and HCV-uninfected
      controls from the Electronically Retrieved Cohort of HCV Infected Veterans
      (ERCHIVES) to compare survival between the two groups. We also compared the
      effect of treatment and treatment duration on survival in the HCV-infected group.
      We used matched Cox proportional hazards model to determine the predictors of
      mortality. Kaplan-Meier survival plots were generated to determine and compare
      survival among HCV-infected and HCV-uninfected persons, and among treated and
      untreated HCV-infected persons.We identified 34,480 matched pairs of HCV-infected
      subjects and controls. HCV infection was independently associated with a higher
      risk of mortality (hazards ratio, 1.37; 95% confidence interval, 1.31-1.47).
      Subjects treated for 48 weeks or longer had the lowest mortality among HCV
      infected subjects (hazards ratio, 0.41; 95% confidence interval, 0.27-0.64),
      whereas those who received less than 48 week of treatment had intermediate
      mortality (hazards ratio, 0.71 and 0.60 for 0-23 weeks and 24-47 weeks of
      treatment, respectively) compared with untreated subjects. CONCLUSION: HCV
      infection is associated with a substantial increase in mortality. Subjects who
      are initiated on treatment, and particularly those who proceed to finish a full
      course of treatment, have significantly reduced risk of mortality. Further
      studies are warranted to determine the effect of virological control on survival.

PMID- 19591130
TI  - Hepatitis B e antigen as a predictor for hepatitis B e antigen-positive chronic
      hepatitis B patients with peginterferon alfa-2a therapy.

PMID- 19591129
TI  - D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a
      prospective, longitudinal, double-blind study of asymptomatic individuals:
      results at 14 years.
AB  - Typical forms of Alzheimer's disease (AD) appear to be influenced by multiple
      susceptibility loci. This report describes the prospective, longitudinal, double
      blind assessment of the age-specific risk of AD encountered by 325 asymptomatic
      first-degree relatives of AD probands who carried the D10S1423 (AD7) 234 bp
      allele, the APOE E4 allele, or both, after 14 years of systematic follow-up. A
      total of 30 incident cases of AD were detected during the first 3752 subject
      years of surveillance. The effects of carrying either or both of the D10S1423 234
      bp and APOE E4 alleles on the age-specific risk of developing AD were determined
      using Kaplan-Meier survival analysis. The risk of developing AD was the greatest
      for individuals who carried both alleles (Mantel-Cox statistic = 16.46, df = 3, P
      = 0.0009; Breslow statistic = 13.38, df = 3, P = 0.004). Cox proportional hazards
      models were developed to estimate the risk ratios for each genotype, controlling
      for the potential effects of age at recruitment, sex, and years of education.
      Only individuals who carried both risk alleles exhibited a risk ratio that
      differed significantly from 1 (risk ratio = 7.5, P = 0.002, 95% CI = 2.1-27.0).
      Neither age at recruitment, sex, nor years of education made significant
      contributions to the model, although women tended to be at greater risk (P =
      0.06). Recent evidence that D10S1423 resides within open reading frame C10orf112,
      whose predicted product resembles a low-density lipoprotein receptor, suggests a
      molecular mechanism for this gene-gene interaction.

PMID- 19591131
TI  - A simple and rapid high-performance liquid chromatography method for
      determination of alendronate sodium in beagle dog plasma with application to
      preclinical pharmacokinetic study.
AB  - A simple and rapid high performance liquid chromatographic (HPLC) method for
      quantifying alendronate in beagle dog plasma was developed, validated and applied
      to a pharmacokinetic study. The sample preparation involved coprecipitation with
      CaCl(2) and derivatization with o-phthalaldehyde. Chromatographic separation was
      achieved on a Diamonsil C(18 )(250 x 4.6 mm, 5 microm) using acetonitrile-0.4%
      EDTA-Na(2) (16:84, v/v) containing 0.034% of NaOH as mobile phase. The
      fluorimetric detector was operated at 339 nm (excitation) and 447 nm (emission).
      The linearity over the concentration range of 5.00-600 ng/mL for alendronate was
      obtained and the lower limit of quantification was 5.00 ng/mL. For each level of
      quality control samples, inter-day and intra-day precisions were less than 8.52
      and 7.42% and accuracies were less than 9.07%. The assay was applied to the
      analysis of samples from a pharmacokinetic study. Following the oral
      administration of 70 mg alendronate sodium to beagle dogs, the maximum plasma
      concentration (C(max)) and elimination half-life were 152 +/- 27.3 and 1.75 +/-
      0.267 h, respectively. The method was demonstrated to be highly feasible and
      reproducible for pharmacokinetic studies.

PMID- 19591133
TI  - Don't miss the forest for the trees.

PMID- 19591132
TI  - Osteoporosis in patients over 50 years of age following restorative
      proctocolectomy for ulcerative colitis: is DXA screening warranted?
AB  - BACKGROUND: Ulcerative colitis (UC) and increasing age are associated with an
      increased risk of osteoporosis. Screening of postmenopausal women and men older
      than 50 years with ulcerative colitis for osteoporosis is recommended. The
      prevalence of osteoporosis in restorative proctocolectomy (RPC) patients more
      than 50 years old is not known. METHODS: Fifty-three consecutive patients older
      than age 50 who had undergone RPC for UC underwent a bone density scan (DXA).
      Sex, smoking status, age at diagnosis of UC, duration of UC, age at RPC, years
      since RPC, age at DXA, and pouch histological inflammatory score were recorded.
      The Kruskal-Wallis test and Spearman's correlation coefficient were used to
      analyze the data. RESULTS: Fifty-three patients were studied; their median age
      was 58 years, and the median age at RPC was 45. The prevalence of osteopenia and
      osteoporosis was 43.4% and 13.2%, respectively. Age at RPC was negatively
      correlated with bone density (P = 0.041, r = 0.281), and there was a negative
      correlation approaching significance with age at the time of DXA (P = 0.071, r = 
      0.250). No other factor studied correlated with bone density. CONCLUSIONS: The
      prevalence of osteoporosis and osteopenia found in this study is similar to that
      reported for UC patients who have not undergone RPC. Patients having RPC should
      be screened in line with current UC guidelines, targeting those older than 50
      years.

PMID- 19591134
TI  - Splenic tuberculosis in a patient with Crohn's disease on infliximab: case
      report.

PMID- 19591135
TI  - General health maintenance in IBD.
AB  - Patients with inflammatory bowel disease (IBD) often rely on their
      gastroenterologist for healthcare maintenance. In addition, the
      gastroenterologist also provides guidance to the patient's primary care physician
      on a broad range of issues such as vaccinations, osteoporosis screening, and
      cancer/dysplasia surveillance. Appropriate vaccinations should be administered to
      patients with IBD, particularly those likely to receive immunosuppression. Live
      virus vaccines are not appropriate for patients on immunosuppressive therapy, and
      therefore should be anticipated and given prior to initiating immunosuppression.
      Screening for osteoporosis is based on a combination of individual risk factors,
      but a history of prolonged (>3 months) steroid use over 10 mg is reason enough to
      obtain dual-energy x-ray absorptiometry scanning. Smoking cessation also falls
      within the realm of the gastroenterologist, as current smoking has a negative
      impact on Crohn's disease and cessation can be related to exacerbation in
      ulcerative colitis. Cancer screening includes not only colorectal cancer, but
      discussion regarding cervical dysplasia, skin cancer, and prostate cancer. Other
      primary care issues include hypertension and cholesterol monitoring, depression,
      and ocular health. A comprehensive understanding of all of the issues that can
      affect a patient with IBD throughout their life cycle is important, as it can
      impact their natural history, medication decisions, and overall outcomes.

PMID- 19591136
TI  - Pulmonary antioxidant defences and protein damage during the ageing process of
      both sexes.
AB  - The free radical theory holds that the senescence is caused by oxidative damage
      that results from an imbalance between reactive oxygen and nitrogen species
      (RONS) and antioxidant defences. Hence, it plays an important role in the field
      of gerontology. We evaluated, in male and female rats, the activities of the
      antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and total
      superoxide dismutase (tSOD), as well as oxidative protein damage in pulmonary
      tissue at 3, 6, 12, and 20 months of age. The results show an increase in the
      activities of all antioxidant enzymes at 12 months of age in female rats,
      suggesting an association with the reproductive life cycle. Protein damage in
      female pulmonary tissues did not change significantly throughout the ageing
      process. In male rats, the activity of GPx in 20 months of age showed an inter
      gender increase, while the tSOD and GPx showed higher activities in 20 months of
      age in the intra-gender analysis. The male lung showed higher protein damage at 6
      months of age. These findings suggest that antioxidant enzymatic activity is
      connected to the reproductive life cycle.

PMID- 19591138
TI  - Colonic ischaemia and intra-abdominal hypertension following open repair of
      ruptured abdominal aortic aneurysm (Br J Surg 2009; 96: 621-627).

PMID- 19591140
TI  - Randomized clinical trial of anal fistula plug versus endorectal advancement flap
      for the treatment of high cryptoglandular fistula in ano (Br J Surg 2009; 96: 608
      612).

PMID- 19591142
TI  - Laparoscopic common bile duct exploration using a rigid nephroscope (Br J Surg
      2009; 96: 412-416).

PMID- 19591144
TI  - Faecal occult blood test-based screening programme with high compliance for
      colonoscopy has a strong clinical impact on colorectal cancer (Br J Surg 2009;
      96: 533-540).

PMID- 19591146
TI  - Long-term outcomes of revisional surgery following laparoscopic fundoplication
      (Br J Surg 2009; 96: 391-397).

PMID- 19591148
TI  - Letter 6: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591149
TI  - Letter 5: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591150
TI  - Letter 4: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591151
TI  - Letter 3: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591152
TI  - Letter 2: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591153
TI  - Letter 1: Randomized clinical trial of antibiotic therapy versus appendicectomy
      as primary treatment of acute appendicitis in unselected patients (Br J Surg
      2009; 96: 473-481).

PMID- 19591155
TI  - Spontaneous rupture of the oesophagus (Br J Surg 2008; 95: 1115-1120).

PMID- 19591157
TI  - Non-heart-beating organ donation.

PMID- 19591158
TI  - Meta-analysis of randomized controlled trials comparing open and laparoscopic
      ventral and incisional hernia repair with mesh.
AB  - BACKGROUND: Laparoscopic ventral and incisional hernia repair has been reported
      in a number of small trials to have equivalent or superior outcomes to open
      repair. METHODS: Randomized controlled trials comparing laparoscopic and open
      incisional or ventral hernia repair with mesh that included data on effectiveness
      and safety were included in a meta-analysis. RESULTS: Eight studies met the
      inclusion criteria. There was no difference between groups in hernia recurrence
      rates (relative risk 1.02 (95 per cent confidence interval (c.i.) 0.41 to 2.54)).
      Duration of surgery varied. Mean length of hospital stay was shorter after
      laparoscopic repair in six of the included studies; the longest mean stay was 5.7
      days for laparoscopic and 10 days for open surgery. Laparoscopic hernia repair
      was associated with fewer wound infections (relative risk 0.22 (95 per cent c.i.
      0.09 to 0.54)), and a trend toward fewer haemorrhagic complications and
      infections requiring mesh removal. CONCLUSION: Laparoscopic repair of ventral and
      incisional hernia is at least as effective, if not superior to, the open approach
      in a number of outcomes.

PMID- 19591159
TI  - Sympathetic nerve damage as a potential cause of lymphoedema after axillary
      dissection for breast cancer.
AB  - BACKGROUND: The physiological disturbances leading to lymphoedema after breast
      cancer surgery are poorly understood. Damage to sympathetic nerves during
      axillary lymph node dissection (ALND), leading to increased capillary fluid
      filtration, was investigated as a possible contributory factor. METHODS: The
      integrity of the upper limb sympathetic nervous system was tested in 36 patients
      before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR),
      calculated from forearm blood flow and mean systemic arterial pressure, was
      measured before and after exposure to lower-body negative pressure. Forearm
      venous compliance was measured using (99m)Tc-labelled autologous erythrocytes and
      radionuclide plethysmography before and after cold water immersion of the feet.
      RESULTS: There were clear changes in FVR and venous compliance in response to
      sympathetic stimulation but no differences attributable to surgery or between the
      nine patients who developed lymphoedema and the 27 who did not; nor were there
      differences between the two arms. There was a trend towards lower preoperative
      FVR in patients who developed lymphoedema. CONCLUSION: Lymphoedema is not the
      result of sympathetic nerve damage sustained during ALND. Preoperative FVR may
      help predict who will get lymphoedema following this surgery.

PMID- 19591160
TI  - N-acetylcysteine prevents neointima formation in experimental venous bypass
      grafts.
AB  - BACKGROUND: Neointima formation, mainly characterized by smooth muscle cell
      proliferation, is an important cause of venous bypass graft failure. The
      therapeutic potential of the antioxidant N-acetylcysteine (NAC) to attenuate
      smooth muscle cell proliferation and neointima formation was examined in vivo.
      The effects of NAC on hyperoxia-induced venous smooth muscle cell (VSMC) cytokine
      production and proliferation were addressed in vitro. METHODS: Rats underwent
      autologous epigastric vein-to-femoral artery interposition grafting. Fourteen
      rats received oral NAC, and a similar control group received saline.
      Histomorphometric analysis was performed after 7 days or 3 weeks. Cytokine
      analysis and cell proliferation assay were performed in cultured human VSMCs
      after hyperoxic or normoxic exposure and NAC administration. RESULTS: NAC-treated
      rats displayed a threefold reduction in neointimal area, a sixfold reduction in
      stenosis rate, and a twofold reduction in VSMC proliferation after vein graft
      surgery. Incubation of VSMCs in 70 per cent oxygen stimulated the release of
      mitogenic inflammatory cytokines interleukin (IL) 6 and IL-8. Cytokine-rich
      medium from these VSMCs induced proliferation of normoxic VSMCs. NAC inhibited
      hyperoxia-induced cytokine release and VSMC proliferation. CONCLUSION: NAC
      attenuated neointima formation and vein graft stenosis by reducing VSMC
      proliferation in vivo, and prevented hyperoxia-induced cytokine production and
      VSMC proliferation in vitro.

PMID- 19591161
TI  - Circumferential suction-assisted lipectomy for lymphoedema after surgery for
      breast cancer.
AB  - BACKGROUND: The incidence of arm lymphoedema after treatment for breast cancer
      ranges from 1 to 49 per cent. Although most women can be treated by non-operative
      means with satisfying results, end-stage lymphoedema is often non-responsive to
      compression, where hypertrophy of adipose tissue limits the outcome value of
      compression or massage. METHODS: This was a prospective study of 37 women with
      unilateral non-pitting lymphoedema. After initial conservative treatment for 2-4
      days, circumferential suction-assisted lipectomy was used to remove excess
      volume. Limb compression was resumed after surgery with short-stretch bandages,
      followed by flat-knit compression garments. RESULTS: The mean preoperative excess
      arm volume was 1399 ml. The total aspirate volume was 2124 ml with 93 per cent
      aspirate adipose tissue content. After 12 months, the mean reduction in excess
      volume was 118 per cent. The percentage reduction in excess volume after 12
      months was linearly related to the preoperative excess volume but showed no
      linear relationship with the duration of lymphoedema or surgeon experience.
      CONCLUSION: Circumferential lipectomy combined with lifelong compression hose is
      an effective technique in end-stage lymphoedema after treatment for breast
      cancer.

PMID- 19591162
TI  - The concept of perihilar cholangiocarcinoma is valid.
AB  - BACKGROUND: The term perihilar cholangiocarcinoma has been used for all tumours
      involving or requiring resection of the hepatic confluence. However, it does not
      distinguish between intrahepatic and extrahepatic hilar tumours, and has no
      clinicopathological basis. This retrospective study examined whether the concept
      of perihilar cholangiocarcinoma is valid clinically. METHODS: Some 250 patients
      with perihilar cholangiocarcinoma were divided into extrahepatic (EHC, 167
      patients) and intrahepatic (IHC, 83) groups based on tumour location.
      Clinicopathological data were compared between these groups. RESULTS: Liver,
      portal vein, venous and lymphatic invasion, and nodal metastasis were more common
      in IHCs than EHCs, whereas histological grade and incidence of perineural
      invasion were similar. IHCs were more advanced at the time of surgery; stage III
      or IV disease was found in 37.7 per cent of EHCs and 59 per cent of IHCs.
      Survival was marginally better for patients with EHCs than for those with IHCs
      (29.3 versus 20 per cent at 5 years; P = 0.057), but survival rates were similar
      for each tumour stage in the American Joint Committee on Cancer classification.
      CONCLUSION: Combining EHC and IHC under the term perihilar cholangiocarcinoma is
      valid, as these tumours have comparable biological behaviour, with similar
      clinical management depending on stage and invasion.

PMID- 19591163
TI  - Lymph node ratio after curative surgery for intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is rare but its incidence is
      rising worldwide. The value of lymph node dissection for ICC is under discussion;
      the current staging systems do not differentiate between numbers of involved
      nodes. METHODS: Ninety-three patients who underwent laparotomy for ICC between
      1997 and 2007 were identified retrospectively; 46 who underwent curative
      resection and systematic lymphadenectomy around the hepatoduodenal ligament were
      analysed further. Univariable and multivariable regression analysis was performed
      to identify prognostic factors. RESULTS: Tumour size and advanced tumour stage
      were associated with worse overall and recurrence-free survival in univariable
      analysis. An increased ratio of positive to total harvested lymph nodes (LNR) was
      also prognostic for adverse outcome in lymph node-positive patients: crude hazard
      ratio 8.93 (95 per cent confidence interval (c.i.) 1.52 to 32.50) for overall
      survival and 8.76 (1.96 to 39.22) for recurrence-free survival. Adjusted hazard
      ratios for LNR in multivariable regression analysis were 9.81 (1.52 to 43.44) and
      10.63 (2.04 to 55.31) respectively. The total number of retrieved lymph nodes was
      not related to survival or recurrence. CONCLUSION: LNR appears to be a good
      prognostic factor for survival or recurrence after curative resection for ICC.

PMID- 19591164
TI  - Ratio of metastatic to resected lymph nodes for prediction of survival in
      patients with inadequately staged gastric cancer.
AB  - BACKGROUND: Staging is inadequate in up to 70 per cent of patients with gastric
      cancer in Western countries owing to the small number of lymph nodes dissected
      during surgery. The aim was to determine whether using the ratio of metastatic to
      resected lymph nodes (LNR) might improve accuracy. METHODS: Data were analysed
      from patients with gastric cancer who had gastrectomy in several centres between
      1986 and 1998, with dissection of 15 or fewer lymph nodes. LNRs and other
      prognostic factors were evaluated. RESULTS: From a total of 738 patients, the
      median number of resected nodes was 8 (range 1-15) and median LNR was 42.8 per
      cent. The number of metastatic nodes significantly affected survival only in
      univariable analysis. In a Cox proportional hazards model, patient age, depth of
      tumour infiltration, tumour location, and LNR were identified as independent
      prognostic factors. Compared with node-negative patients, the hazard ratio for an
      LNR of 0.1-40.0 per cent was 1.85 (P < 0.001), increasing to 2.93 (P < 0.001)
      when the LNR exceeded 40.0 per cent. CONCLUSION: The LNR cannot be used as a
      substitute for staging with adequate lymphadenectomy. It may help to stratify
      patients in terms of prognosis when the number of resected lymph nodes is
      limited.

PMID- 19591165
TI  - Lower oesophageal sphincter dysfunction is part of the functional abnormality in
      epiphrenic diverticulum.
AB  - BACKGROUND: The pathophysiology and management of epiphrenic diverticula remain
      controversial. This study investigated the underlying functional abnormalities
      and long-term results of surgical treatment. METHODS: Patients with symptoms and
      epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV
      fundoplication were reviewed retrospectively. They were assessed before and after
      surgery by radiology, functional testing and endoscopy, and compared with a group
      of 40 normal volunteers. RESULTS: The study included 23 consecutive symptomatic
      patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower
      oesophageal sphincter (LOS) incoordination was considered the most constant
      functional abnormality (P < 0.001). After operation oesophageal diameter
      increased, contraction pressures decreased and peristalsis was reduced. LOS
      resting and gradient pressures decreased (P = 0.001). Despite unchanged acid
      exposure values, endoscopy revealed increased mucosal damage after operation (P =
      0.003). New columnar-lined metaplasia was documented in eight patients (P =
      0.013). Symptoms had decreased after a median of 61 months (P = 0.001).
      CONCLUSION: Epiphrenic diverticulum was associated with spastic dysfunction and
      LOS abnormalities. A long myotomy including the LOS relieved functional
      obstruction and symptoms, but partial fundoplication did not prevent reflux
      damage.

PMID- 19591166
TI  - Systematic review of oxidative stress associated with pneumoperitoneum.
AB  - BACKGROUND: There have been several reports of ischaemic complications after
      routine laparoscopy. The aim of this review was to investigate the relationship
      between this oxidative stress and pneumoperitoneum. METHODS: Medline, Medline in
      process, The Cochrane Library, PubMed and EMBASE were searched for papers on
      oxidative stress and pneumoperitoneum, from 1947 to March 2008 with no language
      restriction or restriction on trial design. Papers that did not investigate
      pneumoperitoneum as a causative factor, or did not report outcome measures
      related to oxidative stress, were excluded. RESULTS: A total of 73 relevant
      papers were identified: 36 animal studies, 21 human clinical trials, nine case
      reports, five review articles and two comments. Pneumoperitoneum causes a
      reduction in splanchnic blood flow, resulting in biochemical evidence of
      oxidative stress in a pressure- and time-dependent manner. There is evidence that
      the use of carbon dioxide for insufflation is contributory. Several measures
      proposed to minimize the oxidative stress have shown promise in animal studies,
      but few have been evaluated in the clinical setting. CONCLUSION: There is an
      increasing body of evidence, mainly from animal studies, that pneumoperitoneum
      decreases splanchnic perfusion with resulting oxidative stress. It is now
      appropriate to investigate the clinical significance of pneumoperitoneum
      associated oxidative stress.

PMID- 19591167
TI  - Treatment of oesophageal anastomotic leaks by temporary stenting with self
      expanding plastic stents.
AB  - BACKGROUND: Oesophageal anastomotic leakage is associated with considerable
      morbidity and mortality. The aim of the present study was to assess the
      feasibility of using temporary self-expanding plastic stents to treat
      postoperative oesophageal leaks. METHODS: Patients with anastomotic leakage after
      abdominothoracic oesophagectomy treated by endoscopic insertion of self-expanding
      plastic stents between 2001 and 2007 were studied. Clinical outcomes were
      analysed, including healing of the leak, morbidity and mortality. RESULTS: Stents
      were inserted successfully in all 22 patients without procedure-related
      complications. Ten patients also required computed tomography-guided drainage
      because surgical drains had been removed. Non-ventilated patients received oral
      nutrition a mean of 4 days after stent placement. Combined treatment with
      stenting and drainage resulted in resolution of the leak in 21 of 22 patients.
      The mean healing time (time to stent removal) was 23 days. Stent migration
      occurred in five of 22 patients, but endoscopic reintervention with placement of
      a new stent was successful in all patients. Repeat thoracotomy with
      intraoperative stent placement was necessary in one patient with an
      oesophagocolonic anastomosis. One patient died in hospital. CONCLUSION: In
      combination with effective drainage, self-expanding plastic stents are an option
      for the treatment of oesophageal anastomotic leaks, and may reduce leak-related
      morbidity and mortality.

PMID- 19591168
TI  - Robot-assisted thoracoscopic oesophagectomy for cancer.
AB  - BACKGROUND: Thoracoscopic oesophagectomy was introduced to reduce the morbidity
      of transthoracic oesophagectomy. The aim was to assess the short- and mid-term
      results of robot-assisted thoracoscopic oesophagectomy for oesophageal cancer.
      METHODS: Between October 2003 and May 2007, 47 patients with resectable
      oesophageal cancer underwent robot-assisted thoracoscopic oesophagectomy.
      Clinical data were collected prospectively. RESULTS: Conversion to thoracotomy
      was necessary in seven patients. Median operating time was 450 min and median
      blood loss 625 ml. Median postoperative ventilation time was 1 day, intensive
      care stay 3 days and hospital stay 18 days. Twenty-one of 47 patients had
      pulmonary complications. Three patients died in hospital. A median of 29 (range 8
      68) lymph nodes was dissected and R0 resection was achieved in 36 patients.
      Twenty-three patients had stage IVa disease. After a median follow-up of 35
      months, median disease-free survival was 15 (95 per cent confidence interval 12
      to 18) months. CONCLUSION: Robot-assisted thoracoscopic oesophagectomy was
      oncologically acceptable. Operating time, blood loss and pulmonary complications
      might decrease with further experience.

PMID- 19591169
TI  - Long-term outcome in patients with adrenal metastases following resection of
      colorectal liver metastases.
AB  - BACKGROUND: The prognostic significance of adrenal metastases (AMs) in patients
      with colorectal liver metastases (CLMs) remains unknown. The aim of this study
      was to determine the influence of AMs on long-term outcome and the role of
      adrenalectomy in patients with CLMs. METHODS: All patients resected for CLMs who
      developed AMs at a single institution between 1992 and 2006 were included in the
      study. Their long-term outcome was compared with that of all other patients
      resected for CLMs but without AMs. RESULTS: Hepatectomy was performed in 796
      patients, of whom 14 (1.8 per cent) developed AMs, a median of 28 months after
      initial diagnosis of CLMs; the remaining 782 patients (98.2 per cent) had no AMs.
      All 14 patients had chemotherapy, and ten went on to adrenalectomy. Median
      survival after diagnosis of CLMs was 50 months in patients with AMs versus 68
      months in those without (P = 0.020). After diagnosis of AMs, median survival was
      23 months, whether or not adrenalectomy was performed. CONCLUSION: The
      development of AMs after liver resection for colorectal cancer deposits carries a
      poor prognosis, and adrenalectomy is probably not warranted.

PMID- 19591170
TI  - Prognostic significance of the expression of MUC1 and collagen type IV in
      advanced gastric carcinoma.
AB  - BACKGROUND: Scirrhous gastric carcinoma is characterized by excessive deposition
      of collagen in the stroma. However, the clinical significance of this fibrosis of
      the stomach has not been clarified. The aim of this study was to examine the
      fibrotic mechanism in several histological types of gastric carcinoma, and the
      combination of MUC1 and collagen type IV as a possible predictor of patient
      survival. METHODS: One hundred and two paraffin-embedded specimens of gastric
      carcinoma were examined by immunohistochemical staining using monoclonal
      antibodies against collagen type IV and MUC1. RESULTS: Collagen type IV-positive
      expression was significantly associated with depth of wall penetration (P =
      0.025) and stage (P = 0.023). There was a significant relationship between MUC1
      positive expression and interstitial collagen type IV-positive expression (P =
      0.035). Survival was shorter for patients with the combination of MUC1-positive
      expression and interstitial collagen type IV-negative expression than for those
      with other expression patterns. CONCLUSION: In patients with differentiated-type
      advanced gastric carcinoma, the combination of MUC1-positive and interstitial
      collagen type IV-negative expression may be a marker of unfavourable prognosis.

PMID- 19591171
TI  - Haemostatic and fibrinolytic factors in men with a small abdominal aortic
      aneurysm.
AB  - BACKGROUND: : The presence of an abdominal aortic aneurysm (AAA) independently
      predicts cardiovascular disease (CVD) and its complications. Levels of plasma
      markers of fibrin turnover are raised in men with a large AAA (at least 5.5 cm)
      and predict CVD risk in healthy subjects. This study examined fibrin turnover in
      men with a small AAA. METHODS: : Seventy-five men with a small AAA (30-55 mm)
      were compared with 90 controls matched for age, sex and race. Haemostatic and
      fibrinolytic parameters were assessed. RESULTS: : Men with a small AAA had higher
      mean levels of fibrinogen (2.92 versus 2.59 g/l; P = 0.019), thrombin
      antithrombin (TAT) complex (4.57 versus 1.89 ng/ml; P < 0.001), prothrombin F1 +
      2 (1.13 versus 0.82 ng/ml; P = 0.004) and D-dimer (346.7 versus 120.2 ng/ml; P <
      0.001). All markers correlated with maximum aortic diameter determined by
      ultrasonography. On multivariable regression the association between presence of
      an AAA and fibrinogen, TAT complex, prothrombin F1 + 2 and D-dimer levels
      remained significant after adjustment for confounding influences. CONCLUSION: :
      Fibrin turnover was increased in these men with a small AAA, independently of
      concomitant CVD, conventional risk factors and inflammatory markers. Enhanced
      fibrin turnover may contribute to the risk of cardiac complications in this
      group.

PMID- 19591172
TI  - Lessons from the battlefield in the management of major trauma.

PMID- 19591173
TI  - RAGE expression and NF-kappaB activation attenuated by extracellular domain of
      RAGE in human salivary gland cell line.
AB  - The receptor for advanced-glycation-end-products (RAGE) has been implicated as a
      pro-inflammatory factor in chronic inflammatory conditions such as diabetes
      mellitus and rheumatoid arthritis. The aim of this study was to investigate the
      inhibitory effect of the soluble-RAGE (sRAGE), the extracellular domain of RAGE,
      on RAGE expression and NF-kappaB translocation in human-salivary gland-cell-lines
      (HSG). Cells were stimulated with agonist S100A4, fusion protein of RAGE
      encompassing the extracellular domain of RAGE (ex-RAGE), ex-RAGE followed by
      S100A4, or S100A4 followed by ex-RAGE. Our study indicates that RAGE expression
      was highest at 150 microg/microl of S100A4 and efficiently down-regulated by 1.8
      fold (P < 0.05) when ex-RAGE was incubated prior to agonist S100A4. RAGE protein
      was also consistently down-regulated by 20-40% with pre-incubation of ex-RAGE.
      More importantly, nuclear translocation of p65 and p52 of NF-kappaB by S100A4 was
      inhibited in the presence of ex-RAGE, confirming anti-inflammatory function of ex
      RAGE. In conclusion, ex-RAGE down-regulates RAGE expression and inhibits p65 and
      p52 activation in HSG, providing evidence that ex-RAGE functions as a "decoy" to
      RAGE-ligand interaction and thus potentially dampening inflammatory conditions.

PMID- 19591174
TI  - NAG7 promotes human nasopharyngeal carcinoma invasion through inhibition of
      estrogen receptor alpha and up-regulation of JNK2/AP-1/MMP1 pathways.
AB  - The NAG7, an estrogen receptor repressor, is a negative regulator of
      nasopharyngeal carcinoma cell growth. Here, we report that NAG7 promotes human
      nasopharyngeal carcinoma invasion, and we identify the mechanisms underlying this
      function. As a consequence of elevated NAG7 expression, the adhesion, migration,
      and invasive capabilities of HNE1 cells in vitro and in vivo were enhanced. NAG7
      was a significant negative regulator of protein expression of estrogen receptor
      alpha (ERalpha), and activated both the JNK2/AP-1/MMP1 and the upstream H-Ras/p-c
      Raf pathways. None of these effects induced by NAG7 over-expression could be
      counteracted by estrogen. These observations indicate that NAG7 plays a potential
      role in promoting nasopharyngeal carcinoma invasion by regulation of ERalpha and
      the H-ras/p-c-Raf and JNK2/AP-1/MMP1 signaling pathways.

PMID- 19591175
TI  - A novel purification method for multipotential skeletal stem cells.
AB  - At least some cells within bone marrow stromal populations are multipotential
      (i.e., differentiate in vitro into osteoblasts, chondrocytes, and adipocytes) and
      thus designated skeletal stem cells (SSCs) or mesenchymal stem cells (MSCs)
      amongst other names. Recently, a subpopulation of stromal cells, notably
      osteoblasts or their progenitors, has been identified as a definitive regulatory
      component of the hematopoietic stem cell (HSC) niche. Thus, the development of
      methods for purifying not only SSCs but cells comprising the HSC niche is of
      interest. Here, we report a method for purifying a novel bone marrow-derived
      population with a high frequency of osteoprogenitors and high expression levels
      of osteoblast differentiation markers (highly purified osteoprogenitors (HipOPs))
      as well as markers of the bone niche for HSCs. In vivo transplantation
      experiments demonstrated that donor HipOPs differentiated into not only
      osteoblasts, osteocytes and cells around sinusoids but also hematopoietic cells.
      Thus, HipOPs represent a novel population for simultaneous reconstruction of bone
      and bone marrow microenvironments.

PMID- 19591176
TI  - Segmental isotopic labeling of a central domain in a multidomain protein by
      protein trans-splicing using only one robust DnaE intein.

PMID- 19591177
TI  - Electrophilic activation of benzaldehydes through ortho palladation: one-pot
      synthesis of 3-methylene-indan-1-ols through a domino allylstannylation/Heck
      reaction under neutral conditions.

PMID- 19591178
TI  - Highly regio- and enantioselective copper-catalyzed hydroboration of styrenes.

PMID- 19591179
TI  - Size-controlled synthesis of conducting-polymer microspheres by pulsed
      sonoelectrochemical polymerization.

PMID- 19591180
TI  - Iron-catalyzed carbonylation: selective and efficient synthesis of succinimides.

PMID- 19591181
TI  - Chemoselectivity in catalytic C-C and C-H bond activation: controlling
      intermolecular carboacylation and hydroarylation of alkenes.

PMID- 19591183
TI  - Synthesis of cyclopamine using a biomimetic and diastereoselective approach.

PMID- 19591182
TI  - Palladium(II)-catalyzed ortho alkylation of benzoic acids with alkyl halides.

PMID- 19591184
TI  - Sensitive and visual detection of adenosine by a rationally designed FokI-based
      biosensing strategy.

PMID- 19591185
TI  - Lasioglossins: three novel antimicrobial peptides from the venom of the eusocial
      bee Lasioglossum laticeps (Hymenoptera: Halictidae).
AB  - Three novel structurally related pentadecapeptides, named lasioglossins, were
      isolated from the venom of the eusocial bee Lasioglossum laticeps. Their primary
      sequences were established as H-Val-Asn-Trp-Lys-Lys-Val-Leu-Gly-Lys-Ile-Ile-Lys
      Val-Ala-Lys-NH(2) (LL-I), H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val
      Ala-Lys-NH(2) (LL-II) and H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val
      Val-Lys-NH(2) (LL-III). These lasioglossins exhibited potent antimicrobial
      activity against both Gram-positive and Gram-negative bacteria, low haemolytic
      and mast cell degranulation activity, and a potency to kill various cancer cells
      in vitro. The lasioglossin CD spectra were measured in the presence of
      trifluoroethanol and sodium dodecyl sulfate solution and indicated a high degree
      of alpha-helical conformation. NMR spectroscopy, which was carried out in
      trifluoroethanol/water confirmed a curved alpha-helical conformation with a
      concave hydrophobic and convex hydrophilic side. To understand the role of this
      bend on biological activity, we studied lasioglossin analogues in which the Gly
      in the centre of the molecule was replaced by other amino acid residues (Ala,
      Lys, Pro). The importance of the N-terminal part of the molecule to the
      antimicrobial activity was revealed through truncation of five residues from both
      the N and C termini of the LL-III peptide. C-terminal deamidation of LL-III
      resulted in a drop in antimicrobial activity, but esterification of the C
      terminus had no effect. Molecular modelling of LL-III and the observed NOE
      contacts indicated the possible formation of a bifurcated H-bond between hydrogen
      from the Lys15 CONH peptide bond and one H of the C-terminal CONH(2) to the Ile11
      oxygen atom. Such interactions cannot form with C-terminal esterification.

PMID- 19591186
TI  - Microarray-based gene expression analysis as a process characterization tool to
      establish comparability of complex biological products: scale-up of a whole-cell
      immunotherapy product.
AB  - Whole-cell immunotherapies and other cellular therapies have shown promising
      results in clinical trials. Due to the complex nature of the whole cell product
      and of the sometimes limited correlation of clinical potency with the proposed
      mechanism of action, these cellular immunotherapy products are generally not
      considered well characterized. Therefore, one major challenge in the product
      development of whole cell therapies is the ability to demonstrate comparability
      of product after changes in the manufacturing process. Such changes are nearly
      inevitable with increase in manufacturing experience leading to improved and
      robust processes that may have higher commercial feasibility. In order to
      comprehensively assess the impact of the process changes on the final product,
      and thus establish comparability, a matrix of characterization assays (in
      addition to lot release assays) assessing the various aspects of the cellular
      product are required. In this study, we assessed the capability of DNA-microarray
      based, gene-expression analysis as a characterization tool using GVAX cancer
      immunotherapy cells manufactured by Cell Genesys, Inc. The GVAX immunotherapy
      product consists two prostate cancer cell lines (CG1940 and CG8711) engineered to
      secrete human GM-CSF. To demonstrate the capability of the assay, we assessed the
      transcriptional changes in the product when produced in the presence or absence
      of fetal bovine serum, and under normal and hypoxic conditions, both changes
      intended to stress the cell lines. We then assessed the impact of an
      approximately 10-fold process scale-up on the final product at the
      transcriptional level. These data were used to develop comparisons and
      statistical analyses suitable for characterizing culture reproducibility and
      cellular product similarity. Use of gene-expression data for process
      characterization proved to be a reproducible and sensitive method for detecting
      differences due to small or large changes in culture conditions as might be
      encountered in process scale-up or unanticipated bioprocess failures. Gene
      expression analysis demonstrated that cell products of representative lots under
      the same production process and at the same production scale were statistically
      identical. Large process changes that resulted from the artificial stress
      conditions used (absence of FBS and induction of hypoxia) displayed profoundly
      different gene expression patterns. We propose the use of simple t-test analysis
      in combination with the herein introduced expression ratio with mean intensity
      (ERMI) analysis as useful tools for process characterization by global gene
      expression analysis.

PMID- 19591188
TI  - Evaluation of beta-alanine- and GABA-substituted peptides as inhibitors of
      disease-linked protein aggregation.

PMID- 19591187
TI  - Chemistry and biology of galactofuranose-containing polysaccharides.
AB  - The thermodynamically less stable form of galactose-galactofuranose (Galf)-is
      essential for the viability of several pathogenic species of bacteria and
      protozoa but absent in this form in mammals, so the biochemical pathways by which
      Galf-containing glycans are assembled and catabolysed are attractive sites for
      drug action. This potential has led to increasing interest in the synthesis of
      molecules containing Galf residues, their subsequent use in studies directed
      towards understanding the enzymes that process these residues and the
      identification of potential inhibitors of these pathways. Major achievements of
      the past several years have included an in-depth understanding of the mechanism
      of UDP-galactopyranose mutase (UGM), the enzyme that produces UDP-Galf, which is
      the donor species for galactofuranosyltransferases. A number of methods for the
      synthesis of galactofuranosides have also been developed, and practitioners in
      the field now have many options for the initiation of a synthesis of
      glycoconjugates containing either alpha- or beta-Galf residues. UDP-Galf has also
      been prepared by a number of approaches, and it appears that a chemoenzymatic
      approach is currently the most viable method for producing multi-milligram
      amounts of this important intermediate. Recent advances both in the understanding
      of the mechanism of UGM and in the synthesis of galactofuranose and its
      derivatives are highlighted in this review.

PMID- 19591189
TI  - A DNAzyme with three protein-like functional groups: enhancing catalytic
      efficiency of M2+-independent RNA cleavage.

PMID- 19591190
TI  - Retro-enantio N-methylated peptides as beta-amyloid aggregation inhibitors.
AB  - An emerging and attractive target for the treatment of Alzheimer's disease is to
      inhibit the aggregation of beta-amyloid protein (Abeta). We applied the retro
      enantio concept to design an N-methylated peptidic inhibitor of the Abeta42
      aggregation process. This inhibitor, inrD, as well as the corresponding all-L
      (inL) and all-D (inD) analogues were assayed for inhibition of Abeta42
      aggregation. They were also screened in neuroblastoma cell cultures to assess
      their capacity to inhibit Abeta42 cytotoxicity and evaluated for proteolytic
      stability. The results reveal that inrD and inD inhibit Abeta42 aggregation more
      effectively than inL, that inrD decreases Abeta42 cytotoxicity to a greater
      extent than inL and inD, and that as expected, both inD and inrD are stable to
      proteases. Based on these results, we propose that the retro-enantio approach
      should be considered in future designs of peptide inhibitors of protein
      aggregation.

PMID- 19591191
TI  - Design, synthesis, and SAR of naphthyl-substituted Diarylpyrimidines as non
      nucleoside inhibitors of HIV-1 reverse transcriptase.
AB  - A series of 38 2-naphthyl-substituted diarylpyrimidine (DAPY) analogues,
      characterized by various substitution patterns on the pyrimidine and naphthalene
      rings, was synthesized in a straightforward fashion by means of parallel
      synthesis and evaluated as inhibitors of the HIV-1 wild-type and double mutant
      (K103N+Y181C) strains. Most of the compounds displayed strong activity against
      wild-type HIV-1. The most active compound, with a cyano group at position C6 on
      the naphthalene ring, exhibited activity against wild-type HIV-1 with an EC50
      value of 0.002 microM and against the double mutant strain with an EC50 value of
      0.24 microM; the selectivity index (SI) against wild-type is >180 000, the
      highest SI value among DAPY analogues. The structure-activity relationship (SAR)
      of the newly synthesized DAPYs is presented herein.

PMID- 19591192
TI  - Shear stress magnitude and duration modulates matrix composition and tensile
      mechanical properties in engineered cartilaginous tissue.
AB  - Cartilage tissue-engineering strategies aim to produce a functional extracellular
      matrix similar to that of the native tissue. However, none of the myriad
      approaches taken have successfully generated a construct possessing the
      structure, composition, and mechanical properties of healthy articular cartilage.
      One possible approach to modulating the matrix composition and mechanical
      properties of engineered tissues is through the use of bioreactor-driven
      mechanical stimulation. In this study, we hypothesized that exposing scaffold
      free cartilaginous tissue constructs to 7 days of continuous shear stress at
      0.001 or 0.1 Pa would increase collagen deposition and tensile mechanical
      properties compared to that of static controls. Histologically, type II collagen
      staining was evident in all construct groups, while a surface layer of type I
      collagen increased in thickness with increasing shear stress magnitude. The areal
      fraction of type I collagen was higher in the 0.1-Pa group (25.2 +/- 2.2%) than
      either the 0.001-Pa (13.6 +/- 3.8%) or the static (7.9 +/- 1.5%) group. Type II
      collagen content, as assessed by ELISA, was also higher in the 0.1-Pa group (7.5
      +/- 2.1%) compared to the 0.001-Pa (3.0 +/- 2.25%) or static groups (3.7 +/-
      3.2%). Temporal gene expression analysis showed a flow-induced increase in type I
      and type II collagen expression within 24 h of exposure. Interestingly, while the
      0.1-Pa group showed higher collagen content, this group retained less sulfated
      glycosaminoglycans in the matrix over time in bioreactor culture. Increases in
      both tensile Young's modulus and ultimate strength were observed with increasing
      shear stress, yielding constructs possessing a modulus of nearly 5 MPa and
      strength of 1.3 MPa. This study demonstrates that shear stress is a potent
      modulator of both the amount and type of synthesized extracellular matrix
      constituents in engineered cartilaginous tissue with corresponding effects on
      mechanical function.

PMID- 19591193
TI  - Refolding of Npro fusion proteins.
AB  - The autoprotease Npro significantly enhances expression of fused peptides and
      proteins and drives the formation of inclusion bodies during protein expression.
      Upon refolding, the autoprotease becomes active and cleaves itself specifically
      at its own C-terminus releasing the target protein with its authentic N-terminus.
      Npro wild-type and its mutant EDDIE, respectively, were fused N-terminally to the
      model proteins green fluorescent protein, staphylococcus Protein A domain D,
      inhibitory peptide of senescence-evasion-factor, and the short 16 amino acid
      peptide pep6His. In comparison with the Npro wild-type, the tailored mutant EDDIE
      displayed an increased rate constant for refolding and cleavage from 1.3 x 10(-4)
      s(-1) to 3.5 x 10(-4) s(-1), and allowed a 15-fold higher protein concentration
      of 1.1 mg/mL when studying pep6His as a fusion partner. For green fluorescent
      protein, the rate constant was increased from 2.4 x 10(-5) s(-1) to 1.1 x 10(-4)
      s(-1) when fused to EDDIE. When fused to small target peptides, refolding and
      cleavage yields were independent of initial protein concentration, even at high
      concentrations of 3.9 mg/mL, although cleavage rates were strongly influenced by
      the fusion partner. This behavior differed from conventional 1st order refolding
      kinetics, where yield strongly depends on initial protein concentration due to an
      aggregation reaction of higher order. Refolding and cleavage of EDDIE fusion
      proteins follow a monomolecular reaction for the autoproteolytic cleavage over a
      wide concentration range. At high protein concentrations, deviations from the
      model assumptions were observed and thus smaller rate constants were required to
      approximate the data.

PMID- 19591194
TI  - Fungal pretreatment of lignocellulose by Phanerochaete chrysosporium to produce
      ethanol from rice straw.
AB  - Phanerochaete chrysosporium is a wood-rot fungus that is capable of degrading
      lignin via its lignolytic system. In this study, an environmentally friendly
      fungal pretreatment process that produces less inhibitory substances than
      conventional methods was developed using P. chrysosporium and then evaluated by
      various analytical methods. To maximize the production of manganese peroxidase,
      which is the primary lignin-degrading enzyme, culture medium was optimized using
      response surface methodologies including the Plackett-Burman design and the Box
      Behnken design. Fermentation of 100 g of rice straw feedstock containing 35.7 g
      of glucan (mainly in the form of cellulose) by cultivation with P. chrysosporium
      for 15 days in the media optimized by response surface methodology was resulted
      in a yield of 29.0 g of glucan that had an enzymatic digestibility of 64.9% of
      the theoretical maximum glucose yield. In addition, scanning electronic
      microscopy, confocal laser scanning microscopy, and X-ray diffractometry revealed
      significant microstructural changes, fungal growth, and a reduction of the
      crystallinity index in the pretreated rice straw, respectively. When the fungal
      pretreated rice straw was used as a substrate for ethanol production in
      simultaneous saccharification and fermentation (SSF) for 24 h, the ethanol
      concentration, production yield and the productivity were 9.49 g/L, 58.2% of the
      theoretical maximum, and 0.40 g/L/h, respectively. Based on these experimental
      data, if 100 g of rice straw are subjected to fungal pretreatment and SSF, 9.9 g
      of ethanol can be produced after 96 h, which is 62.7% of the theoretical maximum
      ethanol yield.

PMID- 19591195
TI  - Structure determination of slowly exchanging conformers in solution using high
      resolution NMR, computational modeling and DFT-GIAO chemical shielding:
      application to an erythronolide A derivative.
AB  - We discuss and demonstrate the potential of HSQC-TOCSY and HSQC-NOESY experiments
      to offer solutions for overlap problems in COSY and NOESY spectra, leading to
      improved signals that can be unambiguously assigned to individual carbons. Direct
      comparison of experimental (1)H and (13)C chemical shielding with density
      functional theory (DFT)-calculated values are uninformative; in contrast, the
      relative differences in experimental shielding between pairs of molecules
      correlates well with the relative differences in DFT-GIAO shielding for the
      computed lowest energy conformers. A detailed application of both experimental
      and theoretical techniques is illustrated for slowly exchanging conformers of an
      erythronolide A derivative, which demonstrates that structure determination can
      strongly benefit from the interplay between experiment and theory.

PMID- 19591196
TI  - Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is
      affected by genetic factors and cholestasis in human liver.
AB  - An important function of hepatocytes is the biotransformation and elimination of
      various drugs, many of which are organic cations and are taken up by organic
      cation transporters (OCTs) of the solute carrier family 22 (SLC22). Because
      interindividual variability of OCT expression may affect response to cationic
      drugs such as metformin, we systematically investigated genetic and nongenetic
      factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver. OCT1 and OCT3
      expression (messenger RNA [mRNA], protein) was analyzed in liver tissue samples
      from 150 Caucasian subjects. Hepatic OCTs were localized by way of
      immunofluorescence microscopy. Matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry and genome-wide single-nucleotide polymorphism
      microarray technology served to genotype 92 variants in the SLC22A1-A3/OCT1-3
      gene cluster. Transport of metformin by recombinant human OCT1 and OCT3 was
      compared using transfected cells. OCT1 mRNA and protein expression varied 113-
      and 83-fold, respectively; OCT3 mRNA expression varied 27-fold. OCT1 transcript
      levels were on average 15-fold higher compared with OCT3. We localized the OCT3
      protein to the basolateral hepatocyte membrane and identified metformin as an
      OCT3 substrate. OCT1 and OCT3 expression are independent of age and sex but were
      significantly reduced in liver donors diagnosed as cholestatic (P < or = 0.01).
      Several haplotypes for OCT1 and OCT3 were identified. Multivariate analysis
      adjusted for multiple testing showed that only the OCT1-Arg61Cys variant
      (rs12208357) strongly correlated with decreased OCT1 protein expression (P <
      0.0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442)
      were associated with reduced OCT3 mRNA levels (P = 0.03). CONCLUSION: We
      identified cholestasis and genetic variants as critical determinants for
      considerable interindividual variability of hepatic OCT1 and OCT3 expression.
      This indicates consequences for hepatic elimination of and response to OCT
      substrates such as metformin.

PMID- 19591197
TI  - Elevated procalcitonin and C-reactive protein as potential biomarkers of sepsis
      in a subpopulation of thrombotic microangiopathy patients.
AB  - Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis
      syndromes associated with multiple pathogenic factors. Deficient activity of
      ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a
      strong rationale for plasma exchange treatment. However, the subset of TMA
      patients with normal ADAMTS13 activity remains a heterogeneous group of patients
      in which the appropriate treatment is not well understood. In addition to the
      common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic
      syndrome, the differential diagnosis of TMA may include sepsis, autoimmune
      disorders, and disseminated intravascular coagulation. Optimal treatment of TMA
      depends on timely recognition of treatable pathogenic factors. We hypothesized
      that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA
      patients. To test this hypothesis, we retrospectively measured the rapid
      biomarkers of sepsis C-reactive protein (CRP) and procalcitonin (PCT), in a
      repository of pretreatment plasma samples from 61 TMA patients treated with
      plasma exchange. Levels were analyzed in 31 severely ADAMTS13-deficient and 30
      ADAMTS13-normal patients. None of the 31 patients with severe deficiency of
      ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non-ADAMTS13-deficient patient
      samples were strongly positive for PCT. These patient samples also had a >10-fold
      higher median CRP level than patients with normal PCT. We conclude that rapid
      assays may help identify sepsis in a subset of TMA patients.

PMID- 19591198
TI  - Peripheral blood stem cell collection in multiple myeloma: a retrospective
      analysis of 6 years leukapheresis activity in 109 patients treated at the
      Istituto Nazionale dei Tumori of Milan.
AB  - Double autologous stem cell transplantation is the standard treatment in newly
      diagnosed multiple myeloma (MM) patients younger than 65 years; therefore,
      optimization of leukapheresis is crucial. We performed a retrospective analysis
      of 297 leukaphereses comparing semiautomated (V4.7 in 20% of collections) versus
      automated (V6.0 in 80%) Caridian (COBE) Spectra versions and analyzing the
      influence of M-protein on the outcome. Both methods gave comparable collection
      efficiencies (CE%) (53.4% vs. 55.7% in V6.0 and V4.7, respectively) with similar
      leukapheresis time and processed volume. Harvest volume was higher in V4.7 (P <
      0.0001) with similar contamination of red blood cells (RBCs) (P = 0.77) and
      platelets (P = 0.09) when compared with V6.0. In patients with higher peripheral
      white blood cells (WBCs), V6.0 with adjusted harvest volume (<700 mL), achieved
      similar CD34(+) CE% (P = 0.39) and better enrichment of nucleated cells (P <
      0.0,002) but higher RBCs (P < 0.0,001) and platelets contamination (P = 0.001),
      when compared with a larger cycle volume in patients with lower WBCs. In hard to
      mobilize patients, CD34(+) CE% was significantly more efficient with V4.7 than
      V6.0 (P < 0.0,001). CD34(+) CE% was unaffected by serologic M-protein, but
      platelet CE% was higher in the absence of M-protein (P = 0.0,003), without any
      reduction in peripheral patients platelets. We, therefore, conclude that in the
      setting of MM patients with a high WBCs count and/or low percentage of peripheral
      CD34(+) cells, collections with V4.7 or adjusted cycle volume V6.0 gave
      comparable result in CD34(+) CE%. RBCs and platelets contamination is higher if
      low cycle volume is chosen. In hard to mobilize patients, V4.7 is advisable.

PMID- 19591199
TI  - Enhanced number and activity of mitochondria in multiple sclerosis lesions.
AB  - Mitochondrial dysfunction has been implicated in the development and progression
      of multiple sclerosis (MS) lesions. Mitochondrial alterations might occur as a
      response to demyelination and inflammation, since demyelination leads to an
      increased energy demand in axons and could thereby affect the number,
      distribution and activity of mitochondria. We have studied the expression of
      mitochondrial proteins and mitochondrial enzyme activity in active demyelinating
      and chronic inactive MS lesions. Mitochondrial protein expression and enzyme
      activity in active and chronic inactive MS lesions was investigated using
      (immuno)histochemical and biochemical techniques. The number of mitochondria and
      their co-localization with axons and astrocytes within MS lesions and adjacent
      normal-appearing white matter (NAWM) was quantitatively assessed. In both active
      and inactive lesions we observed an increase in mitochondrial protein expression
      as well as a significant increase in the number of mitochondria. Mitochondrial
      density in axons and astrocytes was significantly enhanced in active lesions
      compared to adjacent NAWM, whereas a trend was observed in inactive lesions.
      Complex IV activity was strikingly up-regulated in MS lesions compared to control
      white matter and, to a lesser extent, NAWM. Finally, we demonstrated increased
      immunoreactivity of the mitochondrial stress protein mtHSP70 in MS lesions,
      particularly in astrocytes and axons. Our data indicate the occurrence of severe
      mitochondrial alterations in MS lesions, which coincides with enhanced
      mitochondrial oxidative stress. Together, these findings support a mechanism
      whereby enhanced density of mitochondria in MS lesions might contribute to the
      formation of free radicals and subsequent tissue damage.

PMID- 19591200
TI  - Exploring functional roles of multibinding protein interfaces.
AB  - Cellular processes are highly interconnected and many proteins are shared in
      different pathways. Some of these shared proteins or protein families may
      interact with diverse partners using the same interface regions; such
      multibinding proteins are the subject of our study. The main goal of our study is
      to attempt to decipher the mechanisms of specific molecular recognition of
      multiple diverse partners by promiscuous protein regions. To address this, we
      attempt to analyze the physicochemical properties of multibinding interfaces and
      highlight the major mechanisms of functional switches realized through
      multibinding. We find that only 5% of protein families in the structure database
      have multibinding interfaces, and multibinding interfaces do not show any higher
      sequence conservation compared with the background interface sites. We highlight
      several important functional mechanisms utilized by multibinding families. (a)
      Overlap between different functional pathways can be prevented by the switches
      involving nearby residues of the same interfacial region. (b) Interfaces can be
      reused in pathways where the substrate should be passed from one protein to
      another sequentially. (c) The same protein family can develop different
      specificities toward different binding partners reusing the same interface; and
      finally, (d) inhibitors can attach to substrate binding sites as substrate
      mimicry and thereby prevent substrate binding.

PMID- 19591201
TI  - In vivo 1H NMR spectroscopy of the human brain at high magnetic fields:
      metabolite quantification at 4T vs. 7T.
AB  - A comprehensive comparative study of metabolite quantification from the human
      brain was performed on the same 10 subjects at 4T and 7T using MR scanners with
      identical consoles, the same type of RF coils, and identical pulse sequences and
      data analysis. Signal-to-noise ratio (SNR) was increased by a factor of 2 at 7T
      relative to 4T in a volume of interest selected in the occipital cortex using
      half-volume quadrature radio frequency (RF) coils. Spectral linewidth was
      increased by 50% at 7T, which resulted in a 14% increase in spectral resolution
      at 7T relative to 4T. Seventeen brain metabolites were reliably quantified at
      both field strengths. Metabolite quantification at 7T was less sensitive to
      reduced SNR than at 4T. The precision of metabolite quantification and
      detectability of weakly represented metabolites were substantially increased at
      7T relative to 4T. Because of the increased spectral resolution at 7T, only one
      half of the SNR of a 4T spectrum was required to obtain the same quantification
      precision. The Cramer-Rao lower bounds (CRLB), a measure of quantification
      precision, of several metabolites were lower at both field strengths than the
      intersubject variation in metabolite concentrations, which resulted in a strong
      correlation between metabolite concentrations of individual subjects measured at
      4T and 7T.

PMID- 19591202
TI  - Antimicrobial peptide interactions with silica bead supported bilayers and E.
      coli: buforin II, magainin II, and arenicin.
AB  - Using the unique quantitative capabilities of hyperspectral confocal microscopy
      combined with multivariate curve resolution, a comparative approach was employed
      to gain a deeper understanding of the different types of interactions of
      antimicrobial peptides (AMPs) with biological membranes and cellular
      compartments. This approach allowed direct comparison of the dynamics and local
      effects of buforin II, magainin II, and arenicin with nanoporous silica bead
      supported bilayers and living E. coli. Correlating between experiments and
      comparing these responses have yielded several important discoveries for pursuing
      the underlying biophysics of bacteriocidal specificity and the connection between
      structure and function in various cellular environments. First, a novel
      fluorescence method for direct comparison of a model and living system is
      demonstrated by utilizing the membrane partitioning and environmental sensitivity
      of propidium iodide. Second, measurements are presented comparing the temporal
      dynamics and local equilibrium concentrations of the different antimicrobial
      agents in the membrane and internal matrix of the described systems. Finally, we
      discuss how the data lead to a deeper understanding of the roles of membrane
      penetration and permeabilization in the action of these AMPs.

PMID- 19591203
TI  - Combined T2-weighted and diffusion-weighted MRI for diagnosis of urinary bladder
      invasion in patients with prostate carcinoma.
AB  - PURPOSE: To retrospectively determine the diffusion-weighted imaging (DWI)
      characteristics and apparent diffusion coefficient (ADC) values of prostate
      carcinoma (PCa) with urinary bladder invasion, and to compare the accuracy of T2
      weighted MRI alone and T2 combined with DWI for predicting urinary bladder
      invasion. MATERIALS AND METHODS: Sixty-eight patients with proven PCa were
      diagnosed with urinary bladder invasion after conventional magnetic resonance
      imaging (MRI) and DWI (b value = 750 sec/mm(2)) examinations. All the 68 cases
      underwent cystoscopy examination. DWI appearances of all urinary bladder invasion
      and a normal urinary bladder wall were analyzed, and their ADC values were
      measured. T2 images alone and then T2 images combined with DWI were scored for
      the likelihood of urinary bladder invasion on the basis of radiologists' written
      reports. The area under the receiver operating characteristic curve (AUC) was
      used to assess accuracy. Statistical significance was inferred at P < 0.05.
      RESULTS: After cystoscopy examination, 45 (66%) of 68 cases were pathologically
      proven urinary bladder invasion. The mean ADCs for urinary bladder invasion and
      normal urinary bladder wall were (0.963 +/- 0.155) x 10(-3)mm(2)/sec and (1.517
      +/- 0.103) x 10(-3)mm(2)/sec, respectively. The ADC values of urinary bladder
      invasion were significantly lower than those of normal urinary bladder wall (P =
      0.000). The AUC for T2-weighted imaging plus DW imaging (0.861) was significantly
      larger than that for T2-weighted imaging alone (0.734) or for DW imaging alone
      (0.703) (P < 0.001). CONCLUSION: Urinary bladder invasion had lower ADC values
      compared with normal urinary bladder wall. T2 images plus DWI is significantly
      better than T2-weighted imaging alone in the detection of urinary bladder
      invasion in patients with PCa.

PMID- 19591206
TI  - Open retropubic colposuspension for urinary incontinence in women: a short
      version Cochrane review.
AB  - BACKGROUND: Urinary incontinence is a common and potentially debilitating
      problem. Open retropubic colposuspension is a surgical treatment which involves
      lifting the tissues near the bladder neck and proximal urethra in the area behind
      the anterior pubic bones to correct deficient urethral closure. OBJECTIVES: To
      assess the effects of open retropubic colposuspension for the treatment of
      urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence
      Group Specialized Register (searched June 30, 2008) and reference lists of
      relevant articles. We contacted investigators to locate extra studies. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials in women with symptoms
      or urodynamic diagnoses of stress or mixed urinary incontinence that included
      open retropubic colposuspension surgery in at least one trial group. DATA
      COLLECTION AND ANALYSIS: Studies were evaluated for methodological
      quality/susceptibility to bias and appropriateness for inclusion and data
      extracted by two of the reviewers. Trial data were analyzed by intervention.
      Where appropriate, a summary statistic was calculated. MAIN RESULTS: This review
      included 46 trials involving a total of 4,738 women. Overall cure rates were 68.9
      88.0% for open retropubic colposuspension. Two small studies suggest lower
      failure rates after open retropubic colposuspension compared with conservative
      treatment. Similarly, one trial suggests lower failure rates after open
      retropubic colposuspension compared to anticholinergic treatment. Evidence from
      six trials showed a lower failure rate for subjective cure after open retropubic
      colposuspension than after anterior colporrhaphy. Such benefit was maintained
      over time (RR of failure 0.51; 95% CI 0.34-0.76 before the first year, RR 0.43;
      95% CI 0.32-0.57 at 1-5 years, RR 0.49; 95% CI 0.32-0.75 in periods beyond 5
      years). In comparison with needle suspensions there was a lower failure rate
      after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42
      1.03), after the first year (RR 0.48; 95% CI 0.33-0.71), and beyond 5 years (RR
      0.32; 95% CI 15-0.71). Evidence from 12 trials in comparison with suburethral
      slings found no significant difference in failure rates in all time periods
      assessed. Patient-reported failure rates in short, medium and long-term follow-up
      showed no significant difference between open and laparoscopic retropubic
      colposuspension, but with wide confidence intervals. In two trials failure was
      less common after Burch (RR 0.38 95% CI 0.18-0.76) than after the Marshall
      Marchetti-Krantz procedure at 1-5-year follow-up. There were few data at any
      other follow-up time. In general, the evidence available does not show a higher
      morbidity or complication rate with open retropubic colposuspension, compared to
      the other open surgical techniques, although pelvic organ prolapse is more common
      than after anterior colporrhaphy and sling procedures. AUTHORS' CONCLUSIONS: The
      evidence available indicates that open retropubic colposuspension is an effective
      treatment modality for stress urinary incontinence especially in the long term.
      Within the first year of treatment, the overall continence rate is approximately
      85-90%. After 5 years, approximately 70% of patients can expect to be dry. Newer
      minimal access procedures such as tension free vaginal tape look promising in
      comparison with open colposuspension but their long-term performance is not known
      and closer monitoring of their adverse event profile must be carried out.
      Laparoscopic colposuspension should allow speedier recovery but its relative
      safety and effectiveness is not known yet.

PMID- 19591207
TI  - The gold standard.

PMID- 19591209
TI  - Brief communication: self-suckling in Barbary macaque (Macaca sylvanus) mothers
      before and after the death of their infant.
AB  - We report here self-suckling in four wild female Barbary macaques (Macaca
      sylvanus), living in two troops (i.e. "Flat face" and "Large" troop) in the
      middle-Atlas Mountains, Morocco. The four females lost their infants due to
      predation or for unknown causes. Self-suckling was observed before and after the
      infants died in the four females living in the "Flat face" troop. When the
      infants were still alive, self-suckling was of short duration and it was probably
      a method to improve milk flow when the infant switched from one nipple to the
      other. After the infants died, self-suckling lasted significantly longer and the
      females were apparently drinking their own milk. Self-suckling was never observed
      among the four lactating females in the "Large" troop (including one monkey who
      lost her infant) and it could thus represent a cultural difference. Moreover,
      self-suckling after the death of an infant may be explained by the energetic and
      immunological benefits that a monkey may gain from drinking their own milk.
      Finally, self-suckling may have a stress-releasing effect on the mothers who have
      lost their infants.

PMID- 19591208
TI  - Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor
      cells.
AB  - Dose-intensive chemotherapy results in an obligatory period of severe neutropenia
      during which patients are at high risk of infection. While patient support with
      donor neutrophils is possible, this option is restricted due to donor
      availability and logistic complications. To overcome these problems, we explored
      the possibility of large scale ex vivo manufacture of neutrophils from
      hematopoietic progenitor cells (HPC). CD34+ HPC isolated from umbilical cord
      blood (UCB) and mobilized peripheral blood (mPB) were expanded in serum-free
      medium supplemented with stem cell factor, granulocyte colony stimulating factor,
      and a thrombopoietin peptide mimetic. After 15 days of cultivation a 5,800-fold
      expansion in cell number was achieved for UCB, and up to 4,000-fold for mPB,
      comprising 40% and 60% mature neutrophils respectively. Ex vivo expanded
      neutrophils exhibited respiratory burst activity similar to that for donor
      neutrophils, and were capable of killing Candida albicans in vitro. These yields
      correspond to a more than 10-fold improvement over current methods, and are
      sufficient for the production of multiple neutrophil transfusion doses per HPC
      donation. To enable clinical scale manufacture, we adapted our protocol for use
      in a wave-type bioreactor at a volume of 10 L. This is the first demonstration of
      a large scale bioprocess suitable for routine manufacture of a mature blood cell
      product from HPC, and could enable prophylactic neutrophil support for
      chemotherapy patients.

PMID- 19591210
TI  - Body size estimation of small-bodied humans: Applicability of current methods.
AB  - Body size (stature and mass) estimates are integral to understanding the lifeways
      of past populations.Body size estimation of an archaeological skeletal sample can
      be problematic when the body size or proportions of the population are
      distinctive. One such population is that of the Holocene Later Stone Age (LSA) of
      southern Africa, in which small stature (mean femoral length = 407 mm, n = 52)
      and narrow pelves (mean bi-iliac breadth = 210 mm, n = 50) produce a distinctive
      adult body size/shape, making it difficult to identify appropriate body size
      estimation methods. Material culture, morphology, and culture history link the
      Later Stone Age people with the descendant population collectively known as the
      Khoe-San. Stature estimates based on skeletal "anatomical" linear measures (the
      Fully method) and on long bone length are compared, along with body mass
      estimates derived from "morphometric" (bi-iliac breath/stature) and
      "biomechanical" (femoral head diameter) methods, in a LSA adult skeletal sample
      (n = 52) from the from coastal and near-coastal regions of South Africa. Indices
      of sexual dimorphism (ISD) for each method are compared with data from living
      populations. Fully anatomical stature is most congruent with Olivier's femur +
      tibia method, although both produce low ISD. McHenry's femoral head body mass
      formula produces estimates most consistent with the bi-iliac breadth/stature
      method for the females, although the males display higher degrees of disagreement
      among methods. These results highlight the need for formulae derived from
      reference samples from a wider range of body sizes to improve the reliability of
      existing methods.

PMID- 19591211
TI  - Scramble or contest competition over food in solitarily foraging mouse lemurs
      (Microcebus spp.): New insights from stable isotopes.
AB  - The relationships between resource distribution, type of competition, and
      consequences for social organization have been formalized in the socioecological
      model (SEM) which predicts that ecological factors are the main determinants of
      female distribution. We tested this basic prediction in two solitary primates
      (Microcebus berthae and M. murinus) which differ in female association patterns.
      Using stable nitrogen and carbon isotope data of hair samples and food sources we
      quantified inter-specific differences in diet. delta(13)C in M. berthae reflected
      a diet composed mainly of insect secretions. Higher within-species as well as
      seasonal variation in delta(13)C of M. murinus indicated a wider trophic niche
      including plant and animal source food. Constantly elevated delta(15)N in M.
      murinus most likely reflected extended torpor during the lean season. This energy
      saving strategy together with a wider, more opportunistic feeding niche might
      reduce female competition in this species, facilitating smaller female ranges,
      and a higher association potential. In contrast, delta(15)N fluctuated seasonally
      in M. berthae, most likely indicating varying amounts of arthropod food in the
      diet. Intense scramble competition over small and seasonally limited resources
      might lead to female spatial avoidance and a reduced association potential in M.
      berthae. Thus, differences in female association patterns between these two
      solitary foragers are due to different types of competition and overall
      intensities of intra-specific competition.

PMID- 19591212
TI  - Uses and limitations of genetic data relating to Athapaskan migrations: a reply
      to Seymour.

PMID- 19591213
TI  - Stature estimation formulae for indigenous North American populations.
AB  - Stature estimation methods for adult indigenous humans from the Americas have
      generally relied on a limited number of regression equations. The available
      equations, however, are not broadly applicable to the diversity of the
      populations that lived in the New World prior to European colonization.
      Furthermore, some equations that have been used were originally derived from
      inappropriate reference samples, such as the "Mongoloid" group measured by
      Trotter and Gleser (Am J Phys Anthropol 16 [1958] 79-123). This study develops
      new stature estimation equations for long bones of the lower limb from a
      geographically diverse sample of North American archaeological sites. Statures
      were reconstructed from 967 skeletons from 75 archaeological sites using the
      revised Fully anatomical technique (Raxter et al., Am J Phys Anthropol 130 [2006]
      374-384). Archaeological samples were grouped according to general body
      proportions, using relative tibia and femur length to stature as guides. On the
      basis of differences in these proportions, three broad groupings were identified:
      a high latitude "arctic" group, a general "temperate" group, and a Great Plains
      group. Sex-specific ordinary least squares regression formulae were developed
      based on femoral and tibial lengths for each of these groups. Comparisons of the
      new stature estimation equations with previously available equations were
      conducted using several archaeological test samples. In most cases, the new
      stature estimation equations are more precise than those previously available,
      and we recommend their use throughout most of North America. The equations
      developed by Genoves for Mesoamerican and US Southwest samples are a useful
      alternative for these regions. Applicability of the new equations to South
      American samples awaits further testing.

PMID- 19591214
TI  - Brief communication: Restricted geographic distribution for Y-Q* paragroup in
      South America.
AB  - We analyzed 21 paragroup Q* Y chromosomes from South American aboriginal and
      urban populations. Our aims were to evaluate the phylogenetic status, geographic
      distribution, and genetic diversity in these groups of chromosomes and compare
      the degree of genetic variation in relation to Q1a3a haplotypes. All Q*
      chromosomes from our series and five samples from North American Q* presented the
      derivate state for M346, that is present upstream to M3, and determined Q1a3*
      paragroup. We found a restrictive geographic distribution and low frequency of
      Q1a3* in South America. We assumed that this low frequency could be reflecting
      extreme drift effects. However, several estimates of gene diversity do not
      support the existence of a severe bottleneck. The mean haplotype diversity
      expected was similar to that for South American Q1a3* and Q1a3a (0.478 and 0.501,
      respectively). The analysis of previous reports from other research groups and
      this study shows the highest frequencies of Q* for the West Corner and the Grand
      Chaco regions of South America. At present, there is no information on whether
      the phylogenetic status of Q* paragoup described in previous reports is similar
      to that of Q1a3* paragroup though our results support this possibility.

PMID- 19591215
TI  - Obituary: Shelley Rae Saunders (1950-2008).

PMID- 19591216
TI  - Tracing the origins of Hakka and Chaoshanese by mitochondrial DNA analysis.
AB  - Hakka and Chaoshanese are two unique Han populations residing in southern China
      but with northern Han (NH) cultural traditions and linguistic influences.
      Although most of historical records indicate that both populations migrated from
      northern China in the last two thousand years, no consensus on their origins has
      been reached so far. To shed more light on the origins of Hakka and Chaoshanese,
      mitochondrial DNAs (mtDNAs) of 170 Hakka from Meizhou and 102 Chaoshanese from
      Chaoshan area, Guangdong Province, were analyzed. Our results show that some
      southern Chinese predominant haplogroups, e.g. B, F, and M7, have relatively high
      frequencies in both populations. Although median network analyses show that
      Hakka/Chaoshanese share some haplotypes with NH, interpopulation comparison
      reveals that both populations show closer affinity with southern Han (SH)
      populations than with NH. In consideration of previous results from nuclear gene
      (including Y chromosome) research, it is likely that matrilineal landscapes of
      both Hakka and Chaoshanese have largely been shaped by the local people during
      their migration southward and/or later colonization in southern China, and
      factors such as cultural assimilation, patrilocality, and even sex-bias in the
      immigrants might have played important roles during the process.

PMID- 19591218
TI  - Balancing work and life: a conversation with Lesley Forrester. Interview by
      Majlinda Lako and Susan Daher.

PMID- 19591217
TI  - Neural stem cell transplantation benefits a monogenic neurometabolic disorder
      during the symptomatic phase of disease.
AB  - Although we and others have demonstrated that neural stem cells (NSCs) may impact
      such neurogenetic conditions as lysosomal storage diseases when transplanted at
      birth, it has remained unclear whether such interventions can impact well
      established mid-stage disease, a situation often encountered clinically. Here we
      report that when NSCs were injected intracranially into the brain of adult
      symptomatic Sandhoff (Hexb(-/-)) mice, cells migrated far from the injection site
      and integrated into the host cytoarchitecture, restoring beta-hexosaminidase
      enzyme activity and promoting neuropathologic and behavioral improvement. Mouse
      lifespan increased, neurological function improved, and disease progression was
      slowed. These clinical benefits correlated with neuropathological correction at
      the cellular and molecular levels, reflecting the multiple potential beneficial
      actions of stem cells, including enzyme cross-correction, cell replacement,
      tropic support, and direct anti-inflammatory action. Pathotropism (i.e.,
      migration and homing of NSCs to pathological sites) could be imaged in real time
      by magnetic resonance imaging. Differentially expressed chemokines might play a
      role in directing the migration of transplanted stem cells to sites of pathology.
      Significantly, the therapeutic impact of NSCs implanted in even a single location
      was surprisingly widespread due to both cell migration and enzyme diffusion.
      Because many of the beneficial actions of NSCs observed in newborn brains were
      recapitulated in adult brains to the benefit of Sandhoff recipients, NSC-based
      interventions may also be useful in symptomatic subjects with established
      disease.

PMID- 19591220
TI  - Effect of blood group on idiopathic thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a condition caused by deficiency of
      ADAMTS13 resulting in accumulation of ultra large Von Willebrand factor multimers
      (ULVWF), leading to micro thrombi in multiple organs. The varying
      susceptibilities of blood group antigens to ADAMTS13 have been demonstrated. A
      and B antigens are protective of VWF; and VWF purified from blood group O
      individuals has been shown to be cleaved faster by ADAMTS13 compared to VWF from
      blood group AB individuals. We proposed that there may be a difference in the
      incidence of blood groups in TTP patients compared with the general population.
      We felt this to be important for a life-threatening disease with poorly
      understood epidemiology. We report a retrospective analysis of 74 patients
      presenting from 1993 to 2008 with idiopathic TTP. We studied the incidence across
      various blood groups and also estimated the recurrence and mortality in each
      group. The incidence of various blood groups were as follows: O 36%, A 36%, B
      25%, and AB 2%, compared with expected frequencies in the Detroit area: O 44%, A
      33% B 20%, and AB 3%. There was a trend of lower than expected frequency of blood
      group O. There were 24 recurrences and 14 deaths, uniform across blood groups. We
      hypothesized that there may be an association between blood groups and the risk
      of TTP; however the differences in our study were not statistically significant.
      Recurrence and disease specific mortality did not appear to be impacted by blood
      group.

PMID- 19591219
TI  - Fibroblastic colony-forming unit bone marrow cells delay progression to gastric
      dysplasia in a helicobacter model of gastric tumorigenesis.
AB  - Bone marrow mesenchymal stem cells (MSCs) have been shown to have immune
      modulatory effects. Despite efforts to identify these cells in vivo, to date,
      MSCs have been defined mainly by their in vitro cell characteristics. Here, we
      show that Lin(-)CD44(hi)Sca1(-)cKit+CD34(-) cells make up approximately 0.5%-1%
      of murine whole bone marrow cells and yield nearly an equal amount of
      fibroblastic colony-forming units (CFU-F) as whole bone marrow. After
      transplantation into lethally irradiated recipients, Lin(-)CD44(hi)Sca1(
      )cKit+CD34(-) cells engrafted in the bone marrow long-term and demonstrated
      characteristics of MSCs, including capacity to differentiate into osteoblasts and
      adipocytes. To examine whether Lin(-)CD44(hi)Sca1(-)cKit+CD34(-) cells have
      immune modulatory effects, in vitro coculture with activated CD4+ T-cells
      resulted in decreased Th17 cell differentiation by Lin(-)CD44(hi)Sca1(
      )cKit+CD34(-) cells. Furthermore, serial infusions with Lin(-)CD44(hi)Sca1(
      )cKit+CD34(-) cells reduced the progression to low-grade gastric dysplasia in
      mice infected with chronic Helicobacter felis (p = .038). This correlated with
      reduced gastric interleukin (IL)-17F, IL-22, and ROR-gammat gene expression in
      responding mice (p < .05). These data suggest that bone marrow derived Lin(
      )CD44(hi)Sca1(-)cKit+CD34(-) cells have characteristics of MSCs and reduce
      progression of early gastric tumorigenesis induced by chronic H. felis infection.
      The prevention of dysplastic changes may occur through inhibition of Th17
      dependent pathways.

PMID- 19591221
TI  - Effects of protein A immunoadsorption in patients with advanced chronic dilated
      cardiomyopathy.
AB  - OBJECTIVES: The objective of this study was to investigate functional effects of
      immunoadsorption (IA) in severely limited study patients with chronic nonfamilial
      dilated cardiomyopathy (DCM), and to analyze the prevalence of Troponin I (TNI)
      autoantibodies. BACKGROUND: Immunoadsorption (IA) has been shown to induce early
      hemodynamic improvement in patients with nonfamilial DCM. METHODS: We performed
      IA using Immunosorba columns on five consecutive days in 27 patients with chronic
      DCM, congestive heart failure of NYHA class >or=II, left ventricular ejection
      fraction below 40%, and mean time since initial diagnosis of 7.2 +/- 6.8 years.
      RESULTS: Immediately after IA, IgG decreased by 87.7% and IgG3 by 58.5%. Median
      NT-pro BNP was reduced from 1740.0 ng/L at baseline to 1504.0 ng/L after 6 months
      (P = 0.004). Mean left ventricular ejection fraction (LVEF) was not significantly
      improved overall (24.1 +/- 7.8% to 25.4 +/- 10.4% after 6 months, P = 0.38), but
      LVEF improved >or=5% (absolute) in 9 of 27 (33%) patients. Bicycle spiroergometry
      showed a significant increase in exercise capacity from 73.7 +/- 29.4 Watts to
      88.8 +/- 31.1 Watts (P = 0.003) after 6 months while VO2max rose from 13.7 +/-
      3.8 to 14.9 +/- 3.0 mL/min kg after 6 months (P = 0.09). Subgroup analysis
      revealed a higher NT-pro BNP reduction in patients with shorter disease duration
      (P = 0.03) and without TNI autoantibodies at baseline (P = 0.05). All 9 patients
      with an absolute increase of LVEF of >or=5.0% were diabetic (P = 0.0001).
      CONCLUSIONS: In this study, on severely limited heart failure patients with
      nonfamilial DCM, IA therapy moderately improved markers of heart failure severity
      in a limited subgroup of patients. This may be due to the selected study
      population with end-stage heart failure patients and the lower reduction of IgG3
      compared to previous studies. Future blinded multicenter studies are necessary to
      identify those patients that benefit most.

PMID- 19591222
TI  - Immunotherapy for neuroblastoma: turning promise into reality.
AB  - Neuroblastoma is one of the commonest and most aggressive paediatric
      malignancies. The majority of children present with metastatic disease for which
      long-term survival remains poor despite intensive multi-modal therapies. Toxicity
      from current treatment regimes is already significant, and there is little room
      to further intensify therapy. Alternative treatment strategies are therefore
      needed in order to improve survival. Immunotherapy is an attractive therapeutic
      option for these children as it potentially offers a much more specific and less
      toxic treatment than conventional therapies. This review discusses the different
      immunotherapy strategies that may be useful in neuroblastoma, their advantages
      and disadvantages and the challenges that need to be overcome to successfully use
      them clinically.

PMID- 19591223
TI  - Post-transplant EBV-related lymphoproliferative disorder complicating umbilical
      cord blood transplantation in patients of adrenoleukodystrophy.
AB  - EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a well
      recognized complication following solid organ transplantation and hematopoietic
      stem cell transplantation (HSCT) using bone marrow or peripheral blood as stem
      cell sources, but rarely reported in umbilical cord blood transplantation (UCBT).
      We report two cases in unrelated UCBT setting and added the following new
      information to the literature: (i) EBV-related PTLD can be presented late in
      recipients of unrelated UCBT; (ii) in contrast to reported literatures that PTLD
      is a serious complication with unfavorable outcome, especially in monomorphic
      form, our cases showed that the clinical course may be relatively benign if
      treatment is initiated promptly.

PMID- 19591224
TI  - Septic arthritis as the initial manifestation of fatal Vibrio vulnificus
      septicemia in a patient with thalassemia and iron overload.
AB  - Vibrio vulnificus infection is an uncommon but potentially fatal disease in
      children such that prompt recognition has prognostic implications. We describe
      here the case of a 9-year-old female with thalassemia and iron overload who
      presented with septic arthritis as an atypical initial manifestation of fatal V.
      vulnificus septicemia. This report underscores the possibility of septic
      arthritis as an early manifestation of V. vulnificus septicemia. Pediatricians
      should be alert to this extremely invasive disease, especially in children with
      iron overload.

PMID- 19591225
TI  - Noggin elicits retinal fate in Xenopus animal cap embryonic stem cells.
AB  - Driving specific differentiation pathways in multipotent stem cells is a main
      goal of cell therapy. Here we exploited the differentiating potential of Xenopus
      animal cap embryonic stem (ACES) cells to investigate the factors necessary to
      drive multipotent stem cells toward retinal fates. ACES cells are multipotent,
      and can be diverged from their default ectodermal fate to give rise to cell types
      from all three germ layers. We found that a single secreted molecule, Noggin, is
      sufficient to elicit retinal fates in ACES cells. Reverse-transcription
      polymerase chain reaction, immunohistochemistry, and in situ hybridization
      experiments showed that high doses of Noggin are able to support the expression
      of terminal differentiation markers of the neural retina in ACES cells in vitro.
      Following in vivo transplantation, ACES cells expressing high Noggin doses form
      eyes, both in the presumptive eye field region and in ectopic posterior
      locations. The eyes originating from the transplants in the eye field region are
      functionally equivalent to normal eyes, as seen by electrophysiology and c-fos
      expression in response to light. Our data show that in Xenopus embryos, proper
      doses of a single molecule, Noggin, can drive ACES cells toward retinal cell
      differentiation without additional cues. This makes Xenopus ACES cells a suitable
      model system to direct differentiation of stem cells toward retinal fates and
      encourages further studies on the role of Noggin in the retinal differentiation
      of mammalian stem cells.

PMID- 19591226
TI  - Acetylation of sox2 induces its nuclear export in embryonic stem cells.
AB  - Embryonic stem (ES) cells require a coordinated network of transcription factors
      to maintain pluripotency or trigger lineage specific differentiation. Central to
      these processes are the proteins Oct4, Nanog, and Sox2. Although the
      transcriptional targets of these factors have been extensively studied, very
      little is known about how the proteins themselves are regulated, especially at
      the post-translational level. Post-translational modifications are well
      documented to have broad effects on protein stability, activity, and cellular
      distribution. Here, we identify a key lysine residue in the nuclear export signal
      of Sox2 that is acetylated, and demonstrate that blocking acetylation at this
      site retains Sox2 in the nucleus and sustains expression of its target genes
      under hyperacetylation or differentiation conditions. Mimicking acetylation at
      this site promotes association of Sox2 with the nuclear export machinery. In
      addition, increased cellular acetylation leads to reduction in Sox2 levels by
      ubiquitination and proteasomal degradation, thus abrogating its ability to drive
      transcription of its target genes. Acetylation-mediated nuclear export may be a
      commonly used regulatory mechanism for many Sox family members, as this lysine is
      conserved across species and in orthologous proteins.

PMID- 19591227
TI  - Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac
      fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction.
AB  - Recent studies showed that mesenchymal stem cells (MSCs) transplantation
      significantly decreased cardiac fibrosis; however, the mechanisms involved in
      these effects are still poorly understood. In this work, we investigated whether
      the antifibrotic properties of MSCs involve the regulation of matrix
      metalloproteinases (MMPs) and matrix metalloproteinase endogenous inhibitor
      (TIMP) production by cardiac fibroblasts. In vitro experiments showed that
      conditioned medium from MSCs decreased viability, alpha-smooth muscle actin
      expression, and collagen secretion of cardiac fibroblasts. These effects were
      concomitant with the stimulation of MMP-2/MMP-9 activities and membrane type 1
      MMP expression. Experiments performed with fibroblasts from MMP2-knockout mice
      demonstrated that MMP-2 plays a preponderant role in preventing collagen
      accumulation upon incubation with conditioned medium from MSCs. We found that MSC
      conditioned medium also decreased the expression of TIMP2 in cardiac fibroblasts.
      In vivo studies showed that intracardiac injection of MSCs in a rat model of
      postischemic heart failure induced a significant decrease in ventricular
      fibrosis. This effect was associated with the improvement of morphological and
      functional cardiac parameters. In conclusion, we showed that MSCs modulate the
      phenotype of cardiac fibroblasts and their ability to degrade extracellular
      matrix. These properties of MSCs open new perspectives for understanding the
      mechanisms of action of MSCs and anticipate their potential therapeutic or side
      effects.

PMID- 19591228
TI  - Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury
      and supports cardiomyocyte performance.
AB  - The expression pattern of angiotensin AT2 receptors with predominance during
      fetal life and upregulation under pathological conditions during tissue
      injury/repair process suggests that AT2 receptors may exert an important action
      in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute
      ischemia-induced cardiac injury. We aimed here to elucidate the role of AT2
      receptors after acute myocardial infarction. Double immunofluorescence staining
      showed that cardiac AT2 receptors were mainly detected in clusters of small c
      kit+ cells accumulating in peri-infarct zone and c-kit+AT2+ cells increased in
      response to acute cardiac injury. Further, we isolated cardiac c-kit+AT2+ cell
      population by modified magnetic activated cell sorting and fluorescence activated
      cell sorting. These cardiac c-kit+AT2+ cells, represented approximately 0.19% of
      total cardiac cells in infarcted heart, were characterized by upregulated
      transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2,
      Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). When adult
      cardiomyocytes and cardiac c-kit+AT2+ cells isolated from infarcted rat hearts
      were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these
      cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an
      increased c-kit+AT2+ cell population in the infarcted myocardium and reduced
      apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data
      suggest that cardiac c-kit+AT2+ cell population exists and increases after acute
      ischemic injury. AT2 receptor activation supports performance of cardiomyocytes,
      thus contributing to cardioprotection via cardiac c-kit+AT2+ cell population.

PMID- 19591229
TI  - Introducing transcription factors to multipotent mesenchymal stem cells: making
      transdifferentiation possible.
AB  - Multipotent mesenchymal stem cells (MSCs) represent a promising autologous source
      for regenerative medicine. Because MSCs can be isolated from adult tissues, they
      represent an attractive cell source for autologous transplantation. A
      straightforward therapeutic strategy in the field of stem cell-based regenerative
      medicine is the transplantation of functional differentiated cells as cell
      replacement for the lost or defective cells affected by disease. However, this
      strategy requires the capacity to regulate stem cell differentiation toward the
      desired cell fate. This therapeutic approach assumes the capability to direct MSC
      differentiation toward diverse cell fates, including those outside the
      mesenchymal lineage, a process termed transdifferentiation. The capacity of MSCs
      to undergo functional transdifferentiation has been questioned over the years.
      Nonetheless, recent studies support that genetic manipulation can serve to
      promote transdifferentiation. Specifically, forced expression of certain
      transcription factors can lead to reprogramming and alter cell fate. Using such a
      method, fully differentiated lymphocytes have been reprogrammed to become
      macrophages and, remarkably, somatic cells have been reprogrammed to become
      embryonic stem-like cells. In this review, we discuss the past and current
      research aimed at transdifferentiating MSCs, a process with applications that
      could revolutionize regenerative medicine.

PMID- 19591230
TI  - Quantification and prediction of skin pharmacokinetics of amoxicillin and
      cefuroxime.
AB  - The purpose of this project was to develop and validate a pharmacokinetic model
      and to quantify the rate and extent of distribution between plasma and skin of
      two beta-lactam antibiotics, amoxicillin (AMX) and cefuroxime (CFX), which are
      frequently administered systemically to treat skin and skin structure infections.
      Dosing regimens are usually based on plasma concentration, however,
      concentrations at the target site are better correlated with the effect. For each
      antibiotic, three different i.v. bolus doses were administered to three female
      rabbits according to a randomized cross-over design and plasma samples were
      collected serially. Skin concentrations were obtained by continuous
      microdialysis. Skin and unbound plasma concentrations were fitted simultaneously
      using a semi-physiological model and the transfer constants plasma/skin (K(in))
      and skin/plasma (K(out)) were estimated. K(in) and K(out) were then used to
      predict skin concentrations from the plasma levels obtained from an oral
      administration of AMX or from an i.v. bolus of CFX. The predicted skin profiles
      were similar to those measured by microdialysis during the actual experiments. In
      conclusion, this study shows that it is possible to generate a reasonable
      prediction of skin pharmacokinetics from any plasma level once a careful
      characterization of the transfer process between plasma and skin has been made.

PMID- 19591231
TI  - Evaluation of folate-PAMAM for the delivery of antisense oligonucleotides to rat
      C6 glioma cells in vitro and in vivo.
AB  - In the current study, we evaluated the efficiency of folate-polyamidoamine
      dendrimers conjugates (FA-PAMAM) for the in situ delivery of therapeutic
      antisense oligonucleotides (ASODN) that could inhibit the growth of C6 glioma
      cells. Folic acid was coupled to the surface amino groups of G5-PAMAM dendrimer
      (G5D) through a 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide bond, and ASODNs
      corresponding to rat epidermal growth factor receptor (EGFR) were then complexed
      with FA-PAMAM. At an ASODN to PAMAM ratio of 16:1, agarose electrophoresis
      indicated that antisense oligonucleotides were completely complexed with PAMAM or
      FA-PAMAM. The ASODN transfection rates mediated by FA-PAMAM and PAMAM were
      superior to oligofectamine, resulting in greater suppression of EGFR expression
      and glioma cell growth. Stereotactic injection of EGFR ASODN:FA-PAMAM complexes
      into established rat C6 intracranial gliomas resulted in greater suppression of
      tumor growth and longer survival time of tumor-bearing rats compared with PAMAM
      and oligofectamine-mediated EGFR-ASODN therapy. The current study demonstrates
      the suitability of folate-PAMAM dendrimer conjugates for efficient EGFR ASODN
      delivery into glioma cells, wherein they release the ASODN from the FA-PAMAM to
      knock down EGFR expression in C6 glioma cells, both in vitro and in vivo. FA
      PAMAM may thus represent a novel delivery system for short oligonucleotides in
      glioma-targeted therapy.

PMID- 19591232
TI  - In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue
      engineering.
AB  - During the last decades, different materials of both natural and synthetic origin
      have been developed with the aim of inducing and controlling osteogenic
      differentiation of mesenchymal stem cells (MSCs). In order for that to happen, it
      is necessary that the material to be implanted obey a series of requirements,
      namely: osteoconduction, biocompatibility, and biodegradability. Additionally,
      they must be low-priced, easy to produce, shape, and store. Hydroxyapatite (HA)
      is a well known ceramic with a composition similar to the mineral component of
      bone and is highly biocompatible and easy to obtain and/or process. On the other
      hand, collagen is the main structural protein present in the human body and bone.
      In this study, a polymer replication method was applied and a highly porous HA
      scaffold was produced. Collagen was later incorporated to improve the biological
      properties of the scaffold while resembling the bone composition. The scaffolds
      were characterized by means of scanning electron microscopy, Fourier transform
      infrared spectroscopy and energy dispersive spectroscopy. In vitro and in vivo
      testing was performed in all scaffolds produced. The goal of this study was to
      evaluate the in vivo osteogenic potential of MSCs from two different species
      seeded on the different HA basedporous scaffolds with collagen type I. The
      resultsindicate that all scaffolds exhibit relevant bone formation, being more
      prominent in the case of the HA scaffolds.

PMID- 19591233
TI  - Facilitating tissue infiltration and angiogenesis in a tubular collagen scaffold.
AB  - Among different strategies to provide blood supply to tissue-engineered devices
      and implants, the use of arteriovenous loops and bundles has been proposed. The
      aim of this study was to compare the vascularization and healing processes that
      took place in a one-end closed tubular collagen-based scaffold at different
      implantation sites in mice. These conditions were in the presence or absence of
      heparin and/or bone marrow cells. By 30 days, very few cell infiltrations were
      observed in the dorsal subcutaneous and peritoneal implants at any conditions;
      however, the presence of heparin and bone marrow cells improved cell infiltration
      toward an inflammatory reaction. The insertion of an arteriovenous bundle into
      the central cavity of the scaffold resulted in partial wound tissue infiltration
      in the control scaffolds implanted subcutaneously in the hind limb. In similar
      conditions, the presence of bone marrow cells and heparin resulted in dense wound
      tissue with numerous capillaries and a significant amount of newly deposited
      collagen fibers. The design of a central cavity in a porous scaffold with one
      closed end may facilitate invasion from the central part of the implant toward
      the implant wall. In addition, the presence of both a vascular component and
      stem/progenitor cells may lead to a vascularized implant while limiting the
      inflammatory reaction.

PMID- 19591234
TI  - Proliferation and osteogenic differentiation of rat bone marrow stromal cells on
      bioapatite with different crystalline facets.
AB  - The objective of this study is to investigate the attachment, osteogenic
      differentiation, and collagen matrix secretion of rat bone marrow stromal cells
      (MSC) and MC3T3-E1 cells on the biological apatite (Ap) with different
      crystalline facets. The Ap samples with a-facet and c-facet surfaces were
      prepared by cutting the heat-treated cortical bone of bovine femurs parallel and
      perpendicular to the longitudinal direction, respectively. MC3T3-E1 cells
      attached spreading on the a-Ap sample whereas their shape of cells was round on
      the c-Ap. No difference in the proliferation profile of MSC and MC3T3-E1 cells
      was observed between the two samples. The activity of alkaline phosphatase was
      significantly higher for both the cells on the a-Ap sample than that of c-Ap one.
      The matrix of collagen secreted from MC3T3-E1 cells on the a-Ap sample oriented
      along the c-axis of Ap, in contrast to those of c-Ap. The cells tended to align
      along the collagen orientation. It is concluded that the alignment of cells is
      influenced by the collagen fibril orientation of Ap samples.

PMID- 19591235
TI  - A time-based potential step analysis of electrochemical impedance incorporating a
      constant phase element: a study of commercially pure titanium in phosphate
      buffered saline.
AB  - The measurement of electrochemical impedance is a valuable tool to assess the
      electrochemical environment that exists at the surface of metallic biomaterials.
      This article describes the development and validation of a new technique,
      potential step impedance analysis (PSIA), to assess the electrochemical impedance
      of materials whose interface with solution can be modeled as a simplified Randles
      circuit that is modified with a constant phase element. PSIA is based upon
      applying a step change in voltage to a working electrode and analyzing the
      subsequent current transient response in a combined time and frequency domain
      technique. The solution resistance, polarization resistance, and interfacial
      capacitance are found directly in the time domain. The experimental current
      transient is numerically transformed to the frequency domain to determine the
      constant phase exponent, alpha. This combined time and frequency approach was
      tested using current transients generated from computer simulations, from
      resistor-capacitor breadboard circuits, and from commercially pure titanium
      samples immersed in phosphate buffered saline and polarized at -800 mV or +1000
      mV versus Ag/AgCl. It was shown that PSIA calculates equivalent admittance and
      impedance behavior over this range of potentials when compared to standard
      electrochemical impedance spectroscopy. This current transient approach
      characterizes the frequency response of the system without the need for expensive
      frequency response analyzers or software.

PMID- 19591236
TI  - Surface modification of silk fibroin with poly(ethylene glycol) for antiadhesion
      and antithrombotic applications.
AB  - Silk fibroin film surfaces were PEGylated by reaction with cyanuric chloride
      activated poly(ethylene glycol) (PEG). Reactions with different concentrations of
      activated PEG generated films with PEG graft densities from 0.02 to 0.4 mg per
      square cm of silk fibroin. Increased PEGylation resulted in increased
      hydrophilicity as analyzed by contact angle, and a smoother morphology based on
      scanning electron microscopy. Increased PEGylation decreased human IgG adsorption
      and decreased the attachment and proliferation of human fibroblasts over two
      weeks. Increased concentration of PEG on the silk fibroin surfaces also decreased
      the proliferation of human mesenchymal stem cells and inhibited human platelet
      attachment. Surface PEGylated silk fibroin films could be useful antiadhesion and
      antithrombotic materials for biomedical applications when considered along with
      the unique mechanical and tailorable degradation profiles of silk fibroin.

PMID- 19591237
TI  - Functional immobilization of interferon-gamma induces neuronal differentiation of
      neural stem cells.
AB  - Stem cell transplantation provides significant promise to regenerative strategies
      after injury in the central nervous system. Neural stem/progenitor cells (NSPCs)
      have been studied in terms of their regenerative capacity and their ability to
      differentiate into neurons when exposed to various soluble factors. In this
      study, interferon-gamma (IFN-gamma) was compared with brain-derived neurotrophic
      factor (BDNF) and erythropoietin and was shown to be the best single growth
      factor for inducing neuronal differentiation from adult rat brain-derived NSPCs.
      Next, IFN-gamma was surface immobilized to a methacrylamide chitosan (MAC)
      scaffold that was specifically designed to match the modulus of brain tissue and
      neuronal differentiation of NSPCs was examined in vitro by immunohistochemistry.
      Bioactive IFN-gamma was successfully immobilized and quantified by ELISA. Both
      soluble and immobilized IFN-gamma on MAC surfaces showed dose dependent neuronal
      differentiation with soluble saturation occurring at 100 ng/mL and the most
      effective immobilized IFN-gamma dose at 37.5 ng/cm(2), where significantly more
      neurons resulted compared with controls including soluble IFN-gamma.

PMID- 19591238
TI  - Elastic properties of porcine ocular posterior soft tissues.
AB  - We examine the thickness and mechanical properties of the porcine posterior
      retina, choroid, and sclera in different environments and surface directions.
      Vertical and horizontal samples were surgically obtained. Uniaxial experiments
      were performed in room-temperature air, room-temperature saline, and body
      temperature saline. Sample thicknesses were estimated optically. Thickness of all
      layers was found to vary significantly among the samples; thickness standard
      deviation of the mean was 24, 19, and 19% for the retina, choroid, and sclera,
      respectively. Transition stresses and heel moduli of all layers were consistently
      higher in saline than air. The retinal stress-strain relationship in air was
      typically linear with significantly lower horizontal transition strain.
      Transition stresses and moduli of all layers were consistently lower in body than
      room temperature and the differences in the transition stresses and heel moduli
      of the retina and sclera were significant. Also, the sclera had significantly
      lower transition strains in body temperature. These results illustrate the
      importance of testing the tissues at conditions like those found in the body. In
      body-temperature saline, all layers behaved nonlinearly, but only the retina
      exhibited surface anisotropy between the vertical and horizontal directions.

PMID- 19591239
TI  - Influence of direct laser fabrication implant topography on type IV bone: a
      histomorphometric study in humans.
AB  - The aim of this histologic study was to evaluate the influence of the direct
      laser fabrication (DFL) surface topography on bone-to-implant contact (BIC%), on
      bone density in the threaded area (BA%) as well as bone density outside the
      threaded area (BD%) in type IV bone after 8 weeks of unloaded healing. Thirty
      patients (mean age 51.34 +/- 3.06 years) received 1 micro-implant (2.5-mm
      diameter and 6-mm length) each during conventional implant surgery in the
      posterior maxilla. Thirty micro-implants with three topographies were evaluated:
      10 machined (cpTi); 10 sandblasted and acid etched surface (SAE) and 10 DFL micro
      implants. After 8 weeks, the micro-implants and the surrounding tissue were
      removed and prepared for histomorphometric analysis. Four micro-implants (2 cpTi,
      1 SAE and 1DLF) showed no osseointegration after the healing period. Histometric
      evaluation indicated that the mean BIC% was higher for the DFL and SAE surfaces
      (p = 0.0002). The BA% was higher for the DFL surface, although there was no
      difference with the SAE surface. The BD% was similar for all topographies (p >
      0.05). Data suggest that the DFL and SAE surfaces presented a higher bone-to
      implant contact rate compared with cpTi surfaces under unloaded conditions, after
      a healing period of 8 weeks.

PMID- 19591240
TI  - Evaluation of intensity-based ratiometric FRET in image cytometry--approaches and
      a software solution.
AB  - The intensity-based ratiometric FRET (fluorescence resonance energy transfer)
      method is a powerful technique for following molecular interactions in living
      cells. Since it is not based on irreversibly destroying the donor or the acceptor
      fluorophores, the time course of changes in FRET efficiency values can be
      monitored by this method. ImageJ, a sophisticated software tool for many types of
      image processing allows users to extend it with programs for various purposes.
      Implementing intensity-based ratiometric FRET with ImageJ vastly enhances the
      applicability of the FRET method. We developed an efficient ImageJ plugin,
      RiFRET, which calculates FRET efficiency on a pixel-by-pixel basis from
      ratiometric FRET images. It allows the user to correct for channel cross-talk
      (bleed-through) and to calculate FRET from image stacks, i.e., from 3D data sets.
      Semiautomatic processing for larger datasets is also included in the program.
      Furthermore, several options for calibrating FRET efficiency calculations were
      tested and their applicability to various expression systems is discussed.
      Although the ratiometric FRET method is widely applied, our plugin is the first
      freely available software for evaluating such FRET data. The program is user
      friendly and provides reliable, standardized results.

PMID- 19591241
TI  - Application of an efficient strategy based on MAE, HPLC-DAD-MS/MS and HSCCC for
      the rapid extraction, identification, separation and purification of flavonoids
      from Fructus Aurantii Immaturus.
AB  - This study presents an efficient strategy based on microwave-assisted extraction
      (MAE), HPLC-DAD-MS/MS and high-speed counter-current chromatography (HSCCC) for
      the rapid extraction, identification, separation and purification of active
      components from the traditional Chinese medicine Fructus Aurantii Immaturus. An
      LC-DAD-MS/MS method was applied for the screening and structural identification
      of main components in crude extract, and five components were preliminarily
      identified as neoeriocitrin, narirutin, naringin, hesperidin and neohesperidin
      according to their UV and mass spectra. An efficient MAE method for the
      extraction of the three most abundant components (narirutin, naringin and
      neohesperidin) was optimized by the combination of univariate and multivariate
      approaches. The crude extract was then separated and purified by HSCCC and a
      total of 61.6 mg of narirutin, 207.3 mg of naringin and 159.5 mg of neohesperidin
      at high purities of 98.1, 97.2 and 99.5%, respectively, were obtained from 1.42 g
      of crude extract. The recoveries of these compounds were 86, 93 and 89%,
      respectively.

PMID- 19591242
TI  - Solid-phase extraction and analysis of paroxetine in human plasma by ultra
      performance liquid chromatography-electrospray ionization mass spectrometry.
AB  - A rapid, sensitive and rugged solid-phase extraction ultra performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for
      determination of paroxetine in human plasma. The procedure for sample preparation
      includes simple SPE extraction procedure coupled with Hypersil Gold C(18) column
      (100 mm - 2.1 mm, i.d., 1.9 microm) with isocratic elution at a flow-rate of
      0.350 mL/min and fluoxetine was used as the internal standard. The analysis was
      performed on a triple-quadrupole tandem mass spectrometer by multiple reactions
      monitoring mode via electrospray ionization. Using 500 microL plasma, the methods
      were validated over the concentration range 0.050-16.710 ng/mL for paroxetine,
      with a lower limit of quantification of 0.050 ng/mL. The intra- and inter-day
      precision and accuracy of the quality control samples were within 10.0%. The
      recovery was 69.2 and 74.4% for paroxetine and fluoxetine respectively. Total run
      time was only 1.9 min. The method was highly reproducible and gave peaks with
      excellent chromatography properties.

PMID- 19591243
TI  - Synthesis of betulin derivatives and the determination of their relative
      lipophilicities using reversed-phase thin-layer chromatography.
AB  - A series of superlipophilic or highly lipophilic semisynthetic betulin
      derivatives was prepared and their relative lipophilicity was measured by
      reversed-phase thin-layer chromatography (RP-TLC) at different pH values using
      1,4-dioxane-acetate buffer mixtures as mobile phases. Cholesterol, 17beta
      estradiol and pure betulin were used as the reference compounds. Linear
      relationships were found between R(M) values and 1,4-dioxane concentrations in
      the mobile phases. LogP values were also calculated with computer programs
      ACD/LogP (ChemSketch 11.0, Advanced Chemistry Development Inc.) and ClogP
      (Daylight Chemical Information Systems Inc.). The empirical and theoretical data
      were compared, and the R(M0) values correlated well with logP. Two of the
      synthesized betulin derivatives are reported for the first time.

PMID- 19591244
TI  - Sensitive determination of protein based on the fluorescence enhancement effect
      of terbium (III)-epinephrine-protein-sodium dodecylsulfate system.
AB  - It was found that the fluorescence of Tb(3+)-epinephrine (E) complex can be
      enhanced by both bovine serum albumin (BSA) and sodium dodecylsulfate (SDS), and
      stabilized by ascorbic acid (AA). It is considered that the fluorescence
      enhancement of the Tb(3+)-E-BSA-AA-SDS system originates not only from the
      hydrophobic microenvironment provided by BSA-SDS, but also from the energy
      transfer from BSA to Tb(3+) in this system. Therefore, a new fluorescence method
      for the determination of protein concentrations as low as 1.3 x 10(-9) g mL(-1)
      BSA is established using Tb(3+)-epinephrine complex as probe. The method has been
      applied for the determination of BSA and human serum albumin in actual samples,
      and the results obtained are satisfactory. Compared with other fluorescence
      methods, this method is simpler and more sensitive for the determination of
      protein. The mechanism of the fluorescence enhancement of the system is studied
      in detail.

PMID- 19591245
TI  - Labeling of BSA and imaging of mouse T-lymphocyte as well as mouse spleen tissue
      by L-glutathione capped CdTe quantum dots.
AB  - L-glutathione capped highly fluorescent CdTe quantum dots (QDs) were prepared by
      an aqueous approach and used as fluorescent labels to link albumin bovine serum
      (BSA) and rat anti-mouse CD4, which was expressed on mouse T-lymphocyte and mouse
      spleen tissue. The sharp and narrow emission peaks showed that the as-prepared
      QDs have desirable dispersibility, uniformity and good fluorescence properties.
      Both CdTe-BSA and CdTe-CD4 conjugates showed an enhancement of fluorescence
      intensity over that of bare CdTe QDs. The experimental result of gel
      electrophoresis confirmed the successful conjugation of CdTe-BSA and CdTe-CD4.
      The fluorescent microscopic images of CdTe-CD4 labeled mouse T-lymphocyte cells
      and mouse spleen tissue were compared with that obtained from fluorescein
      isothiocyanate labeling. It was demonstrated that the CdTe QDs-based probe
      exhibited much better photostability and fluorescence intensity than fluorescein
      isothiocyanate, showing a good application potential in the immuno-labeling of
      cells and tissues.

PMID- 19591247
TI  - Severe cerebral toxoplasma infection cannot be  excluded by a normal CT scan.
AB  - A fatal case is reported concerning a severely immunocompromised 50-year-old
      female renal transplant recipient who developed fever and confusion. Cerebral
      imaging with contrast-enhanced computed tomography (CT) scans showed no
      abnormalities while subsequently performed magnetic resonance imaging (MRI )
      showed clear abnormalities in the basal ganglia. By that time serology and
      polymerase chain reaction had confirmed the diagnosis of cerebral toxoplasmosis.
      Because of the suboptimal sensitivity of these tests negative results should be
      handled with care. Once cerebral toxoplasmosis is suspected in at-risk patients,
      treatment should be started empirically pending the confirmation of the
      diagnosis. A normal cerebral CT scan does not preclude cerebral toxoplasmosis.In
      these situations MRI can give important additional information.

PMID- 19591248
TI  - Contributions to microbiology. Bacterial sensing and signaling. Foreword.

PMID- 19591246
TI  - Effects of summer training camp on serum opsonic activity and plasma cytokine
      levels in female long-distance runners.
AB  - In a summer training camp, strenuous physical exercises are carried out to
      improve endurance ability. The effects of the training stress on the immune
      system have been studied extensively. However, less attention has been paid to
      non-specific immunological changes. Serum opsonic activity (SOA) is a more direct
      and suitable indicator of non-specific humoral immunity. In this study, we used
      the luminal-dependent chemiluminescence (LmCL) to measure reactive oxygen species
      generation from pooled human neutrophils as an indicator of SOA. We also measured
      plasma myeloperoxidase (MPO) and plasma cytokine levels. Twenty-two female
      college runners took part in this study after giving their written informed
      consent. There was no significant difference in the physical characteristics and
      serum enzyme levels. However, significant differences were observed in the
      changes of blood property and plasma cytokine levels. According to MPO levels,
      neutrophils in vivo may be deactivated during the camp. Positive correlations
      between fluctuations of pro- and anti-inflammatory cytokine levels were observed
      in this study. According to the results of peak time and peak height of LmCL, SOA
      seems to increase at first qualitatively and then quantitatively during the
      summer camp. The increased SOA level may compensate for the decrease in
      neutrophil activity.

PMID- 19591249
TI  - Progress towards   poliomyelitis eradication   in India, January 2007-May   2009.

PMID- 19591250
TI  - Cincinnati doctors before Daniel Drake, 1788-1807.

PMID- 19591251
TI  - Technological innovation in the United States.
AB  - This paper presents nearly three and a half centuries of American invention, and
      is particularly concerned with primary invention as distinct from development,
      production, and service engineering. One apparent but not real exception to this
      statement is that one section will be devoted to the American invention of
      production engineering. Various factors have stimulated, guided, and inhibited
      American inventiveness; indeed, colonial status during nearly half the historical
      period being examined all but stifled technological innovation. It will also
      become clear that American disenchantment with basic scientific activity
      diminished the relative magnitude of her innovations after the advent of the
      technique of applied research in Europe following the middle of the nineteenth
      century. This circumstance is particularly obvious in the cases of chemical and
      electrical engineering, the first of the applied sciences.

PMID- 19591252
TI  - Nineteenth century New Orleans: its public health ordeal.

PMID- 19591253
TI  - When did a man in the Renaissance grow old?

PMID- 19591254
TI  - Notice of inadvertent duplicate publication.

PMID- 19591255
TI  - The evolution controversy in North Carolina, 1920-1927.

PMID- 19591256
TI  - Influenza and inflation in Tudor England.

PMID- 19591257
TI  - The Sheppard-Towner Act: progressivism in the 1920s.

PMID- 19591258
TI  - Observations on the dental pathology seen in ancient Egyptian skulls.

PMID- 19591259
TI  - A letter by Carl Linnaeus to von Haller.

PMID- 19591260
TI  - The practice of dentistry in ancient Egypt.

PMID- 19591262
TI  - An eighteenth century American medical manuscript: the clinical notebook of John
      Archer, M.B., 1768.

PMID- 19591261
TI  - Where in the world is ASRA AcutePOP?
AB  - Progress continues on American Society of Regional Anesthesia (ASRA) AcutePOP.
      Highlights include selection of data fields and creation of definitions for
      complications jointly accepted by clinical registries for ASRA, American Society
      of Anesthesiologists, Regional Anesthesia Surveillance System, Society for
      Obstetric Anesthesia and Perinatology, and Society for Pediatric Anesthesia.
      Development of a Web site and applications continues, and a demonstration is
      planned for the ASRA 2009 meeting.

PMID- 19591263
TI  - Adam Cunningham's Atlantic crossing, 1728.

PMID- 19591265
TI  - Thomas Parke's student life in England and Scotland, 1771-1773.

PMID- 19591264
TI  - Nicholas Collin's Appeal to American scientists.

PMID- 19591266
TI  - The diary of John Casaubon.

PMID- 19591268
TI  - [Senile degeneration and the future prospects of anti-aging medicine].

PMID- 19591267
TI  - Putting the mouth back in the body: improving oral health across the
      Commonwealth.

PMID- 19591269
TI  - [Anti-aging medicine].

PMID- 19591270
TI  - [Mechanisms underlying the aging process and the anti-aging strategy].
AB  - The mechanisms underlying the aging process and the anti-aging strategy in
      mammals are discussed by reviewing accumulated findings of the anti-aging effect
      of calorie restriction (CR), longevity assurance genes, and progerias. An
      evolutionary view emphasizes the roles of energy--sensing and neuroendocrine
      adaptation to food shortage as the mechanisms underlying the effect of CR. In
      mammals, genetic changes that reduce the growth hormone (GH)-IGF-1 axis or
      mitochondrial respiration favor longevity. Progeria models also indicate
      importance of the reduced hormonal signals including the GH-IGF-1 axis and
      mitochondrial respiration as protective mechanisms against cellular stresses
      induced by genetic instability. The findings described clearly indicate sites of
      action for the anti-aging strategy.

PMID- 19591271
TI  - [Genetic polymorphism related to diversity of the individual aging].
AB  - In recent years, the advancements in aging research have led to a deeper
      understanding of the aging process and have also greatly changed our perception
      towards aging. In addition, the Human Genome Project has provided information on
      the human genome and has provided a study base for the elucidation of the
      molecular mechanisms underlying aging. It is interesting to note that the
      causative gene of Hutchinson-Gilford progeria syndrome was identified at the same
      period of the Human Genome Project completion, and it was expected that all the
      genes related to the human aging process would be identified. However, many
      phenomena regarding the molecular mechanisms underlying aging still remain
      unknown. Understanding these mechanisms is necessary in order to control aging
      process.

PMID- 19591272
TI  - [WRN gene].
AB  - Werner's syndrome is a typical progeroid syndrome with many specific features of
      aging early in life. Clinical features of Werner's syndrome closely resemble
      accelerated aging, such as cataract, scleroderma skin, diabetes and
      tumorigenesis. The causative gene of this syndrome is denoted as WRN, which
      encodes a homolog of the E. coli RecQ DNA helicase and is located on chromosome
      8p2-p11.2. WRN is not only a helicase but also an exonuclease and ATPase. WRN
      protein plays a key role in genome stability, particularly during DNA replication
      and telomere metabolism. In this review, we introduce the clinical
      characteristics of Werner's syndrome and recent topics concerning WRN in
      comparison with other progeroid syndromes.

PMID- 19591273
TI  - [Aspects of mammalian aging from alphaklotho study].
AB  - Since the discovery of alphaklotho-mutant mice, it has been questioned whether
      the responsible gene, alphaklotho, makes any effect on 'intrinsic aging' process.
      So far we found that alphaKlotho regulates transcellular calcium transport by
      mediating Na,K-ATPase activity and dominates mineral-regulating hormones such as
      PTH, vitamin D and FGF23. A new concept is now emerged that alphaklotho
      integrates mineral homeostasis. Findings of human cases with mineral disorders
      revealed impairment of alphaklotho expression as a pathological cause. Mineral
      metabolic system contributes to health and thus its disruption should result in
      acceleration of aging and disease.

PMID- 19591274
TI  - [Sir2 gene].
AB  - In Japan, the ratio of people 65 years old and over against total population is
      about 22 % and we face a critical problem of aging population. Accumulating
      evidence in the world suggests that Sirt1, an NAD(+)-dependent protein
      deacetylase, plays an important role in modulation of aging. We discuss a
      potential therapeutic target, Sirt1 and challenge for prevention of age-related
      diseases (Alzheimer's dementia, osteoporosis, sarcopenia, arteriosclerosis and
      cancer).

PMID- 19591275
TI  - [Telomere].
AB  - We reviewed correlations among telomere length, aging and carcinogenesis.
      Southern blot analysis showed that telomere shortening occurred with aging in all
      human tissues except for brain and myocardium. We investigated the telomere
      lengths of individual cell types in human tissues using a Q-FISH method and an
      original software package, "Tissue Telo". Q-FISH revealed that in squamous
      epithelia, NTCR corresponding to telomere length was significantly highest in
      basal cells and lowest in prickle cells, and that telomere length regressed at a
      certain rate in each cell type except for fibroblasts. Mean telomere length was
      significantly less in background tissue squamous epithelia of patients with
      cancer than in normal controls without cancer. We demonstrated telomere
      shortening and chromosomal instability in the background and normal control with
      excessively shortened telomeres. The data suggest that cancer arises from
      epithelial cells with short telomeres.

PMID- 19591276
TI  - [Mitochondrial genome and longevity].
AB  - In humans, mitochondrial DNA (mtDNA) is a 16,569-bp double-stranded circular
      molecule, encoding 37 genes, and is exclusively transmitted from the mother.
      According to the recent findings from many studies of mitochondrial diseases
      caused by nuclear gene mutations, the accumulation of somatic mtDNA mutations in
      tissues has been expected to contribute toward age-associated mitochondrial
      dysfunction and a life span.

PMID- 19591277
TI  - [Molecular mechanism of accelerating ageing by oxidative stress].
AB  - Reactive oxygen species are important for many life sustaining processes of cells
      and tissues, but they can also induce cell damage and death. If their production
      and levels within cells are not effectively controlled, then the detrimental
      effects of oxidative stress can accumulate. Oxidative stress is widely thought to
      underpin many ageing processes, and the oxidative stress theory of ageing is one
      of the most widely acknowledged theories of ageing. As well as being the major
      source of reactive oxygen species, mitochondria are also a major site of
      oxidative damage. The purpose of this review is a concise and current review of
      the role of oxidative stress in ageing process. Emphasis is placed upon the roles
      of mitochondrial proton leak, the uncoupling proteins, and the anti-ageing
      effects of caloric restriction.

PMID- 19591278
TI  - [The mechanisms whereby insulin/IGF-1 signaling regulates aging and longevity].
AB  - There is a conserved mechanism in all living organisms whereby overnutrition
      negatively regulates lifespan, while loss of function mutations in the genes
      encoding insulin/IGF-1 signaling molecules also independently shorten lifespan in
      worms and flies. However, in mammals, same mutations sometimes result in severe
      metabolic disorders and shorter lifespan, although knockout mice with disruption
      of some insulin/IGF-1 signaling molecules display prolonged lifespan. Moreover,
      obesity-induced diabetes and metabolic syndrome are also associated with shorter
      lifespan despite the decreased insulin signaling in liver and skeletal muscle.
      This is presumably because hyperinsulinemia in obese animals and humans enhances
      insulin signaling in particular tissues which determine aging and longevity. It
      is also likely that overnutrition suppresses AMP kinase and increase mTOR
      activity, contributing to the shorter lifespan in obese subjects.

PMID- 19591279
TI  - [Mitochondrial dysfunction as a promoting factor of senescence].
AB  - Mitochondria not only produce the cell's ATP using oxygen, but also act as a
      major source of reactive oxygen species (ROS). ROS are generated as by-products
      in normal oxidative metabolism, and are eliminated by antioxidants in ordinary
      circumstances. Mitochondrial dysfunction induces the increase of ROS generation,
      and excess ROS injure the genes, proteins and lipids in mitochondria and cells
      (oxidative stress). Particularly, oxidative damages to mitochondrial DNA provoke
      further mitochondrial respiratory chain damage and oxidative stress. Oxidative
      damages in mitochondria and cells are increased during aging, therefore
      mitochondrial dysfunction and oxidative stress play crucial roles in promoting
      senescence. Mitochondria are important targets for anti-aging.

PMID- 19591280
TI  - [Age-related decline of immune function and age-related diseases].
AB  - Effects of aging on immune system are widespread. The development of T and B
      cells declines with age. The functions of matured T and B cell also decline with
      age. Consequently, infections present major clinical problems for elderly
      patients. Many of age-related diseases are related to innate immunity. For
      example, the pathogenesis of atherosclerosis and Alzheimer disease are related to
      macrophages (microglia). The Ox-LDL or A-beta induces macrophages or microglia to
      produce inflammatory cytokines, chemokines and matrix metalloproteinases.
      Recently neutrophils have been shown to be an important immune cells in
      atherosclerosis. Neutrophils secrete inflammatory cytokines. In wound healing
      neutrophils also work as first important immune cells, which affect age-related
      decline of wound repair.

PMID- 19591281
TI  - [Role of the environmental factors on aging].
AB  - Aging is a process of irreversible decline in physiological function over the
      time. Several postulated mechanisms for aging include cumulative DNA damage,
      mitochondrial dysfunction, telomere loss, altered gene expression, and oxidative
      damages. Those factors affecting the aging process were implicated in
      hypertension, diabetes, lipid metabolic disorder, heart failure, smoking and
      psychological stress and so on. Subjects with those disorders are manifested the
      increased insulin resistance and oxidative stress which are more likely to
      accelerate aging, atherosclerosis and premature death. Both are also associated
      with accelerated telomere attrition in leucocytes and chronicle the cumulative
      burden of oxidative stress and inflammation over a life course. Here, recent
      evidences including our data about the relationship between telomere attrition
      and age-related disorders are introduced. Finally, we identify improving life
      style as well as pharmacological interventions as potent anti-aging effects to be
      important for keeping of healthy long life.

PMID- 19591282
TI  - [Evidence for and against anti-aging effects based on model animal studies].
AB  - Exciting recent findings are remarkable extension of lifespan of model animals in
      which single genes are mutated. Studies on model animals have provided valuable
      as well as limited and often misleading information in understanding human aging
      and anti-aging practice. It is important to realize that extension of lifespan
      and retardation of aging processes are two different things in principle, the
      latter being apparently more important for improving QOL in human. Discussed here
      are selected topics on the limitation of model animal studies and potential
      problems of popular anti-oxidants. Also discussed are caloric restriction and
      exercise that have anti-aging effects in rodents that might be translated into
      human but with limitations.

PMID- 19591283
TI  - [Clues to the exceptional longevity --morbiditiy and functional status of Tokyo
      area centenarians].
AB  - Recent studies documented that most centenarians were survivors with multiple
      comorbidities. We examined morbidities and physical and cognitive function of 302
      Japanese centenarians living in Tokyo, and assessed the association between
      morbidities and functional status. Most centenarians have chronic diseases such
      as hypertension, heart disease, and stroke. Notably, the prevalence of diabetes
      mellitus was very low compared with middle-aged Japanese adults. Stroke and
      fracture were significantly associated with poorer physical and cognitive
      function. Higher blood pressure, higher serum total cholesterol concentration and
      higher serum high-density lipoprotein cholesterol concentration were associated
      with better physical and cognitive function. It seems that the oldest-old might
      be less affected with conventional risk factors, such as hypertension and
      hypercholesterolemia, at least in terms of functional status. This phenomenon
      might be one of the "centenarian paradox".

PMID- 19591284
TI  - [Sampling and early measure devised to deal with high-risk patients].
AB  - To evaluate high-risk group in the elderly is very important. Elderly itself is
      high-risk, and elderly patients show higher frequencies of cardiovascular
      diseases, falling and fracture, dementia and impairment of activity of daily life
      (ADL). To evaluate high-risk for cardiovascular diseases, arterial stiffness
      measured by pulse wave velocity and atherosclerosis measured by carotid
      echography are very useful. To evaluate prognosis of elderly patients,
      comprehensive geriatric assessment (CGA) is quite useful tool. We evaluated
      prognosis of gastroenterological surgery using CGA. Patients with mild depression
      evaluated by geriatric depression score worsened their ADL after
      gastroenterological surgery, however, the presence of dementia did not influence
      on ADL after surgery.

PMID- 19591285
TI  - [Evaluating the degree of aging: current situations and future perspectives].
AB  - Degree of aging can be evaluated using various indications, such as genetics
      (telomere etc.), cellular markers, and clinical judgments. Along with increased
      practice of clinical aging checkups, such as Health and Longevity Checkup
      ("Kenkou-Jyumyou Dock") and Anti-aging Checkup ("Kokarei Dock"), a database on
      aging is currently being developed among the Japanese population. With this
      database, we are gaining better understanding of each marker's standard values
      and the correlations between diversified factors like hs-CRP and other
      inflammatory factors, oxidative stress, bone-vessel correlations, diagnostic
      imaging etc. In the future, verifying these indications in intervention trials
      would be the key to establish anti-aging as a part of medical science.

PMID- 19591286
TI  - [Effects of exercise and physical activity on vital age].
AB  - Advances in medical care have enabled many middle-aged and older adults to live
      for long periods of time. However, considerable variability is present among
      those people with regards to both longevity and physical health status. Physical
      inactivity is a significant risk factor for many chronic diseases, while exercise
      habituation is beneficial for the maintenance of good health and high vitality.
      The authors have developed the concept of so-called vital age for the assessment
      of health and functional status in middle-aged and older adults. The vital age is
      estimated using a variety of bio-medical, primarily cardiovascular risk factor
      parameters. Previous research has compared vital age between sedentary persons
      and those with obesity and chronic diseases and between sedentary persons and
      those with exercise habituation, and found that exercise habituation can
      certainly contribute to better physical vitality in previously sedentary persons
      as well as diseased persons.

PMID- 19591287
TI  - [Anti-aging effects by caloric restriction].
AB  - Caloric restriction (CR) in experimental animals shows to extend the lifespan of
      animals with the decreased frequency of age-related diseases. CR also produces
      beneficial health effects in monkeys and humans. These benefits include improved
      insulin sensitivity, enhanced stress resistance, decreased cancer incidence, and
      increased neuronal function and neurogenesis. Several important signal
      transduction pathways have been implicated in the regulation of the physiological
      processes of CR leading to increased lifespan. One of these pathways includes the
      Sirt1 pathway. Sirt1 deacetylates a large number of transcriptional factors and
      cofactors involved in cell growth, differentiation, stress resistance, oxidative
      damage, and metabolism. Recently, several studies report that resveratrol and
      other compounds exogenously activate Sirt1 protein and improve the obesity
      associated pathology in mice. In this text, we introduce the recent topics of CR
      research and discuss the anti-aging effects by CR.

PMID- 19591288
TI  - [Anti-aging medicine: the evidence to the value of the antihypertensive drugs,
      hypoglycemic drugs and statins].
AB  - Aging is associated with a large increase in the prevalence and incidence of
      arteriosclerotic diseases including cerebrovascular disease and coronary artery
      disease. Prevention of arteriosclerosis is a major challenge in order to increase
      longevity of populations. Hypertension, diabetes and dyslipidemia are known as
      lifestyle-related diseases and risk factors for arteriosclerosis. The tight
      control of blood pressure, glucose and LDL cholesterol is important in preventing
      arteriosclerosis. Many clinical trials have been revealed pleiotropic effects
      among antihypertensive drugs, hypoglycemic drugs and statins, and these effects
      are useful for anti-aging. Selection of appropriate medicines to manage the risk
      factors would be a way to prevent senescence.

PMID- 19591289
TI  - [Antioxidants as anti-ageing medicine].
AB  - As a mechanism of the ageing becomes clear by the scientific study, it has been
      believed that oxidative stress is an accelerator of the ageing. Still it is too
      critical to take antioxidants in large quantities for anti-ageing, and it should
      be needed to clarify the efficacy of anti-oxidative therapy by the scientific
      evidence. In this chapter, we explained it to positioning of the antioxidant for
      general anti-ageing strategy, Sara about the present conditions of the molecular
      mechanism elucidation study on effects of the antioxidant.

PMID- 19591290
TI  - [Anti-aging drugs].
AB  - The mechanisms of aging are still largely a mystery. However, recent studies
      using yeast, C. elegans, and Drosophila show that longevity can be altered by
      genetic manipulations. Moreover, drugs increase lifespan of these organisms have
      been identified. An anticonvulsant ethosuximide, antidepressants such as
      mianserin, antioxidants, an inhibitor of histone deacetylase, and resveratrol, a
      Sir2 activator, significantly extend lifespan of some organisms. Although these
      drugs have not been reported to extend lifespan of mammals, they provide
      molecular cues to elucidate aging mechanisms.

PMID- 19591291
TI  - [Psychotherapy].
AB  - The human being faces social, physical, and mentally various changes with aging.
      It is a view of anti-aging to maintain the quality of life, to improve and to aim
      at a healthy long life in such change that is not avoided. For example, the loss
      of social roles will be experienced more often. Moreover, the fall of a physical
      function is felt and it comes to experience the anxiety over illness or death.
      Thus, in experience that "the thing" which there was commonly loses, comes to
      feel loneliness, depressive mood, and sadness. In this paper, we want to
      introduce about the psychotherapy as a purpose which maintains a healthy mental
      activity, taking such the elderly people psychology into consideration.

PMID- 19591292
TI  - [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].
AB  - The ability to maintain active and independent living as long as possible is
      crucial for the healthy longevity. Hormones responsible for some of the
      manifestations associated with aging are growth hormone, insulin-like growth
      factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and
      thyroid hormones. These hormonal changes are associated with changes in body
      composition, visceral obesity, muscle weakness, osteoporosis, urinary
      incontinence, loss of cognitive functioning, reduction in well being, depression,
      as well as sexual dysfunction. With the prolongation of life expectancy, both men
      and women today live the latter third life with endocrine deficiencies. Hormone
      replacement therapy may alleviate the debilitating conditions of secondary
      partial endocrine deficiencies by preventing or delaying some aspects of aging.

PMID- 19591293
TI  - [Regenerative medicine for anti-aging].
AB  - Regenerative medicine refers to research and treatments that restore damaged
      tissues. It consists of three factors: cells, chemical substances, and scaffolds.
      One of its purposes is rejuvenation, and from this point of view, it really
      resembles anti-aging medicine. Recently, studies concerning stem cells such as
      embryonic stem cells (ES) and induce pluripotent stem cells (iPS) have made
      remarkable progress and seem promising, but are still far from clinical use. In
      contrast, we introduce a few examples of anti-aging medicine using regenerative
      medicine methods that have been applied successfully in clinical use such as
      cultured fibroblast, adipose tissue derived stem cells and platelet rich plasma
      (PRP), and continue researching cultured dermal papilla cells.

PMID- 19591294
TI  - [Gene therapy for anti-aging medicine].
AB  - Better understanding of the mechanism of aging, particularly in vivo mice or C.
      elegans, will have an important impact on drug discovery for several kinds of
      human diseases. In the history of gene therapy, the initial target diseases were
      cancer or congenital diseases. However, since the concept of therapeutic
      angiogenesis had been proposed, the cardiovascular diseases were currently new
      targets of gene therapy. We used the naked plasmid of hepatocyte growth factor
      (HGF) as an angiogenic factor for peripheral arterial diseases, and showed the
      efficacy and safety in clinical trial. Recent reports suggest that HGF has an
      anti-inflammatory action and attenuated cellular senescence. Thus, HGF gene
      therapy might be an anti-aging therapy in cardiovascular diseases.

PMID- 19591295
TI  - [Anti-aging dock].
AB  - Our anti-aging center (AAC) began providing health check-up services to local
      citizens in western Japan in February 2006, with the mission of promoting
      'successful' aging through the employment of anti-aging check-ups, termed 'anti
      aging dock' in Japan, using evidence-based 'anti-aging dock' strategies designed
      to diagnose atherosclerosis based on personal data. Clinical test items routinely
      received by most patients are as follows: 1) general physical measurement, 2)
      blood tests and urine analysis, 3) brain MRI/MRA, 4) carotid ultrasound imaging,
      5) visceral fat area (VFA) estimation by abdominal CT, 6) brachial ankle pulse
      wave velocity (baPWV), 7) bone mineral density measurement, 8) stabilometer
      testing, 9) cognitive function testing, and 10) optional tests, including
      ambulatory blood pressure monitoring (ABPM). Data from patients providing written
      informed consent has been used for research. As of December, 2008, the total
      number of patients has exceeded 1,000. About 50 participants (5%) were found to
      have cerebral aneurysm, as diagnosed using 3.0 tesla MRI. Of these, 10 patients
      required surgery, 7 in our hospital and 3 in an affiliated hospital. About 5% of
      participants were evaluated as probably having dementia; in particular, three
      patients required treatment for Alzheimer disease. With regard to research, we
      have focused on the association between cerebral microbleeds and atherosclerotic
      disease, and the clinical implications of a high ankle-brachial index (ABI).

PMID- 19591296
TI  - [The metabolic syndrome; a target for antiaging medicine].
AB  - Overnutrition and inactivity can lead to obesity, impaired glucose tolerance,
      dyslipidemia, and hypertension, a cluster of diseases known as the metabolic
      syndrome. Insulin resistance and dysregulation of adipocytokines are the
      fundamentals of this syndrome. It is well documented that advancing age is
      associated with increased body fat and blunted insulin action, however,
      centenarians, who are the best model of successful aging, had a preserved insulin
      sensitivity and better adipocytokine profiles. It is also demonstrated that
      adipocytokine dysregulation can lead sarcopenia and frailty in the oldest old.
      These observations suggested that preservation of adipose endocrine function by
      means of lifestyle modification may be potentially important for maintaining
      health and function and promoting survival at an extremely old age.

PMID- 19591297
TI  - [Regulation of cellular senescence by Bach1].
AB  - The tumor suppressor p53 induces cellular senescence, an irreversible form of
      proliferation arrest, to inhibit carcinogenesis as well as aging of organs and a
      body. While the major cause of cellular senescence and aging is oxidative stress,
      little is known about how the p53 activity is regulated under such conditions.
      Bach1 inhibits expression of oxidative stress responsive genes by competing with
      Nrf2, the key activator of oxidative stress response. Bach1 inhibits p53
      dependent cellular senescence induced by oxidative stress. Bach1 forms a protein
      complex with p53, is recruited to p53 target genes, and inhibits their
      expression. These findings provide completely novel insights into how the
      activity of p53 is regulated under oxidative stress. Since p53 is the critical
      tumor suppressor with huge clinical implications, the newly identified mechanism
      should open new research fields.

PMID- 19591298
TI  - [Recent advances in cell and gene therapies for Parkinson's disease].
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically
      characterized by movement abnormalities. Selective loss of nigrostriatal
      dopaminergic neurons is the pathological hallmark of PD. Currently most
      prevailing treatment is oral administration of dopamine-related compounds,
      however, the prolonged drug treatment causes adverse side effects such as
      dyskinesia. ector-mediated in vivo gene therapy is now going to provide novel
      therapeutic options. In this review, we will focus on history and recent clinical
      trials in cell and gene therapies and discuss novel approaches for the treatment
      of inherited and sporadic forms of PD.

PMID- 19591299
TI  - [Combination therapy of ARB with diuretics in Japanese hypertensive patients].
AB  - The new guideline for the management of hypertension issued by the Japanese
      Society of Hypertension (JSH2009) emphasizes strict blood pressure (BP) control.
      Ca channel blockers (CCB) and angiotensin receptor blockers (ARB) are mainly used
      in Japan, while BP control status remains insufficient. Since the achievement of
      salt restriction to less than 6 g/day is difficult in Japanese hypertensive
      patients, the use of low dose diuretics is useful. To minimize metabolic side
      effects of diuretics, combination therapy with ARB or ACE inhibitors is
      warranted. Losartan/HCTZ combination tablets effectively reduce BP when switched
      from the usual dose of ARB or ACE inhibitors. Since losartan has a property to
      increase urinary uric acid excretion, it may offset the increase in serum uric
      acid induced by the use of HCTZ. Metabolic disorders including diabetes,
      dyslipidemia and hyperuricemia are commonly prevalent in hypertensive patients.
      Thus, strict BP control utilizing appropriate combination therapy and the
      concomitant control of other metabolic risk factors are important to prevent
      cardiovascular events.

PMID- 19591300
TI  - The times they are a-changin'--quickly.

PMID- 19591301
TI  - First responders after disasters: a review of stress reactions, at-risk,
      vulnerability, and resilience factors.
AB  - Disasters are widely reported, commonplace events that characteristically leave
      an enormous legacy of human suffering through death, injury, extensive
      infrastructural damage, and disorganization to systems and communities. The
      economic costs may be almost incalculable. Professional and civilian first
      responders play a vital role in mitigating these effects. However, to maximize
      their potential with the minimum health and welfare costs to first responders, it
      is important to have a good understanding of the demands of such work on them,
      how they cope, and what enables them to fulfill their roles. This review will
      explore these themes by highlighting important findings and areas of uncertainty.

PMID- 19591302
TI  - New York City's healthcare transportation during a disaster: a preparedness
      framework for a wicked problem.
AB  - During a disaster, victims with varied morbidities are located at incident sites,
      while healthcare facilities with varied healthcare resources are distributed
      elsewhere. Transportation serves an essential equilibrating role: it helps
      balance the patients' need for care with the supply of care. Studying the special
      case of New York City, this article sets out the healthcare transportation
      components as: (1) incident morbidity; (2) transportation assets; and (3)
      healthcare capacity. The relationship between these three components raises an
      assignment problem: the management of healthcare transportation within a dynamic
      and partly unpredictable incident-transportation-healthcare nexus, under urban
      disruption. While the routine dispatch problem can be tackled through better
      geographic allocation software and technical algorithms, the disaster assignment
      problem must be confronted through real-time, mutual adjustment between
      institutions. This article outlines institutional alternatives for managing the
      assignment problem and calls for further research on the merits of alternative
      institutional models.

PMID- 19591303
TI  - Ethical considerations of research in disaster-stricken populations.
AB  - Recently, emphasis has been placed on improving and expanding research in
      disaster response and the treatment of disaster-stricken populations. However,
      research in these settings presents unique ethical challenges with which the
      scientific and biomedical ethics communities continue to struggle. At the core of
      the controversy is the question of how best to balance the critical need for
      research with the equally important obligation to respect and protect the
      interests of research participants within the unique stress of a disaster. This
      concern stems from the potential of increased vulnerability of individuals
      stricken by disaster over and above their usual vulnerability to risk and
      exploitation as research subjects. Ethical principles that must be considered in
      these situations are the same as those that are important when conducting any
      human research: respect for persons, non-maleficence, beneficence, and justice.
      This paper explores the ethical challenges that accompany inadequate resources
      and personnel, the potential vulnerability of research participants, the dual
      role of physician-researcher, and the importance of the public's perception and
      trust are explored. It then proposes a number of potential avenues through which
      to conduct ethically justifiable research that could answer many of the pressing
      questions in disaster medicine and response.

PMID- 19591304
TI  - Ethical considerations for emergency care providers during pandemic influenza-
      ready or not...
AB  - When an infectious pandemic occurs in the United States, emergency care providers
      (ECPs) will be on the frontlines caring for infected, potentially infected, and
      non-infected patients. Logistically, the current emergency care system is not
      ready for a pandemic, but are the providers ethically ready? Some of the most
      difficult and challenging issues that will be raised during a pandemic will be
      ethical in nature. An ECP likely will be confronted with ethical values and value
      conflicts underlying restriction of liberty, duty to care, and resource
      allocation. This report summarizes the ethical concerns and challenges that ECPs
      face during an infectious pandemic, and raises ethical questions that may arise
      related to the role of an ECP as a healthcare provider and stakeholder.

PMID- 19591305
TI  - Out-of-hospital cardiac arrest: first documented experience in a Mexican urban
      setting.
AB  - OBJECTIVE: Out-of-hospital cardiac arrest is one of the leading causes of death
      in Mexico, but many survival and prognostic factors are unknown. The aim of this
      study was to assess out-of-hospital cardiac arrest in a Mexican city. METHODS:
      This was a prospective, cohort study that evaluated the records of the major
      ambulance services in the city of Queretaro, Mexico. Means, standard deviation,
      and percentages for the categorical variables were obtained. Logistic regression
      was performed to determine the effects between interventions, times, and return
      of spontaneous circulation (ROSC). RESULTS: For an 11-month period, 148 out-of
      hospital cardiac arrest cases were recorded. The mean age of the victims was 54
      +/- 22.6 years and 90 (65.3%) were males. Forty-nine cases were related to
      cardiac disease, 46 to other disease, 27 to trauma, 18 to terminal illnesses, and
      three to drowning. Twelve (8.6%) patients had a pulse upon hospital arrival, but
      none survived to discharge. No victims were defibrillated prior to ambulance
      arrival. The collapse-assessment interval was 22.5 +/- 19:1 minutes, the mean
      value for the ambulance response times was 13:6 +/-10:4 minutes. Basic emergency
      medical technicians applied chest compressions to 40 victims (27.2%), controlled
      the airway in 32 (21.8%), and defibrillated seven (4.8%). Chest compressions and
      airway control showed an OR of 8 and 12 respectively for ROSC. CONCLUSIONS: The
      poor survival rate in this study emphasizes the need to improve efforts in
      provider training and public education. Authorities must promote actions to
      enhance prehospital emergency services capabilities, shorten response times, and
      provide community education to increase the chances of survival for out-of
      hospital cardiac arrest victims in Mexico.

PMID- 19591306
TI  - Effect of the rural rescue system on reducing the mortality rate of landmine
      victims: a prospective study in Ilam Province, Iran.
AB  - BACKGROUND: In several Iranian provinces, there are large numbers of landmines
      that threaten the lives of many civilians. Ilam is one of the most polluted areas
      with 1,086 injuries from landmines between 1989 to 1999, with an overall
      mortality rate of 36.4%. A remarkable number of deaths occurred before the
      injured were conveyed to the hospital. In this survey, the effects of on trauma
      outcome of the use of prehospital trauma life support provided by trained
      paramedics and rural health workers as first responders were examined. METHODS:
      In an interventional, prospective study, 4,834 persons (general physicians,
      nurses, rural health workers, and emergency technicians, high- and low-educated
      people, layperson villagers, and nomads) were trained in one level of advanced
      (for general physicians and nurses) and four levels of basic life support courses
      during two years (2000-2001). Following the training, the data from 288 landmine
      victims who were referred to the main hospital in Ilam (trauma center) were
      registered prospectively (2001-2005). The effects of prehospital trauma life
      support training were assessed by using the Injury Severity Scale (ISS) score and
      prehospital physiologic severity (PSS) score. RESULTS: There were 288 injuries
      from landmines in the Mehran region between 2002 and 2005. The mean ISS score was
      20.3 with a median of 13. Forty percent were severely injured with an ISS score
      >15. Of the injured who received prehospital care at the Mehran Emergency Center,
      the mean value of the PSS scores was 6.40, which improved to 7.43 in the hospital
      (p = 0.01; 95% CI for difference -0.72 to -0.45), in comparison with 5.97 in the
      injured who were conveyed to Ilam Hospital directly (mean of ISS was
      approximately equal in both groups). The total mortality rate was 27% between
      2001 and 2005. CONCLUSIONS: Prehospital educations and training help improve PSS
      scores and reduce the death toll of landmine accidents in the remote areas.

PMID- 19591307
TI  - Reducing landmine mortality rates in Iran using public medical education and
      rural rescue teams--what can be learned from landmine casualties, and how can the
      situation be improved?

PMID- 19591308
TI  - Experience of health-related problems during house parties in the Netherlands:
      nine years of experience and three million visitors.
AB  - OBJECTIVE: The objective of this study was to report on a nine years of
      experience of providing medical support during house parties (raves) in the
      Netherlands, where they can be organized legally. DESIGN: This was a prospective,
      observational study of self-referred patients from 1997 to 2005. During raves,
      first aid stations are staffed with specifically trained medical and paramedical
      personnel. Self-referred patients were diagnosed, treated, and recorded using
      standardized methods. RESULTS: During a nine-year period with 219 raves occurred,
      involving approximately three million participants, 23,581 patients visited the
      first aid stations. The medical usage rate (MUR) varied from 59-170 patients per
      10,000 rave participants. The mean age increased from 1997 to 2005 from 18.7 +/-
      2.7 to 23.3 +/- 5.7 years. The mean stay at the first aid station was 18 +/- 46
      minutes. Most health problems were mild. Fifteen cases of severe incidents were
      observed with one death. CONCLUSIONS: Unique data from the Netherlands
      demonstrate a low number of serious, health-related, short-term problems during
      raves.

PMID- 19591309
TI  - Transport and use of point-of-care ultrasound by a disaster medical assistance
      team.
AB  - The role of ultrasound in disaster medicine has not been not well established.
      This report describes the transport and use of point-of-care ultrasound by a
      Disaster Medical Assistance Team (DMAT) responding to a mass-casualty incident
      due to a cyclone. Ultrasound-competent physicians on the team were able to use
      portable ultrasound on cyclone casualties to exclude intra-abdominal hemorrhage,
      pericardial fluid, pneumothoraces, and hemothoraces. Information obtained using
      ultrasound made initial patient management, and subsequent decisions regarding
      triage for transport safer and based on more detailed clinical information.

PMID- 19591310
TI  - A periapical image of a lower first molar.

PMID- 19591311
TI  - Implied threat to specialist expertise.

PMID- 19591312
TI  - IDA promoting best practice.

PMID- 19591313
TI  - Medical emergencies in dental practice.
AB  - Serious medical emergencies are fortunately a rare occurrence in the dental
      practice environment; however, if an emergency situation is encountered a delay
      in treatment may result in potentially avoidable consequences. The risk of
      mortality or serious morbidity can be reduced by ensuring that basic emergency
      equipment and medications are in place, and that the dental team is appropriately
      trained in basic life support measures. This article aims to provide an overview
      of the basic emergency medications and equipment that should be present in dental
      practices, and to discuss specific responses to some of the more common adverse
      medical events that can present while providing dental treatment.

PMID- 19591315
TI  - Restorative implant dentistry.

PMID- 19591316
TI  - Tax planning for dentists.

PMID- 19591314
TI  - Alveolar lymphangioma in infants: report of two cases.
AB  - The alveolar lymphangioma is a benign but relatively rare condition found only in
      the oral cavities of black infants. Dentists practising in Ireland may be unaware
      of this condition due to its racial specificity. This paper presents two case
      reports of multiple alveolar lymphangiomas found in black infants in a children's
      hospital in Ireland. The epidemiology, aetiology, clinical presentation,
      histology, and management options are discussed. The photographs should aid the
      practitioner in recognising these lesions.

PMID- 19591317
TI  - Cross-border healthcare: a patient's choice.
AB  - Going abroad for medical treatment is not new and 'health tourism' is a growing
      trend with estimates suggesting that as many as 150,000 Britons choose this
      option. A European Directive being proposed could increase those numbers.

PMID- 19591318
TI  - What a difference a drain makes.

PMID- 19591319
TI  - God on the NHS.

PMID- 19591320
TI  - Patient anxiety and conscious surgery.
AB  - The amount of surgery undertaken on the conscious patient is increasing. However,
      many patients are anxious and resistant to such surgery. Patients (n = 214) were
      surveyed to determine their related apprehensions. Being awake, feeling or seeing
      the body cut open and experiencing pain all increased anxiety. The potential for
      insufficient information provision was also a source of concern. Formal
      management of intraoperative apprehension may help limit anxiety and expel
      apparent misapprehensions.

PMID- 19591321
TI  - A review of operating department practitioner preceptorship.
AB  - This project aimed to review current practice within a large National Health
      Service teaching hospital and to provide a rationale for implementing a change to
      existing working practice. At the time, operating department practitioners only
      received a period of mentorship as part of the Trust induction course. There is
      evidence to support changes to current practices in the directorate with a view
      to implementing a more structured preceptorship programme.

PMID- 19591322
TI  - Use of drains in surgery: a review.
AB  - Drains have been used in surgery for several years to remove body fluids thereby
      preventing the accumulation of serous fluid and improving wound healing. Drains
      may be classified as closed or open systems, and active or passive depending on
      their intended function. Closed vacuum drains apply negative suction in a sealed
      environment, producing apposition of tissues and thus promoting healing. Correct
      assessment of clinical indications might reduce unnecessary usage. This article
      will introduce the principles and practice of various types of drains and
      highlight the importance of understanding how surgical drains promote quality
      patient care.

PMID- 19591323
TI  - Obstetric surgery for perioperative staff and midwives.
AB  - Where a pregnant woman experiences trauma or has acute surgical needs there are
      additional concerns for the well being of both the woman and her foetus. This
      article explores obstetric procedures for the pregnant woman and discusses the
      implications for perioperative staff and midwives.

PMID- 19591324
TI  - Dame Hilda Lloyd: first president of the Royal College of Obstetricians and
      gynaecologists.
AB  - Since earliest times, women have been looked after by women in their
      confinements. By the Middle Ages the profession of the female midwife, often an
      experienced older woman, was well recognised. The service of a male doctor was
      often frowned upon. Indeed, in 1522 a Dr Wertt of Hamburg was burned at the stake
      for attending a delivery dressed as a woman.

PMID- 19591325
TI  - Fact or fiction?

PMID- 19591326
TI  - Contemporary oral and maxillofacial surgery.

PMID- 19591327
TI  - Arthrocentesis for the treatment of internal derangements of the
      temporomandibular joint.
AB  - Internal derangements of the temporomandibular joint (TMJ) are characterized by
      displacement of the intra-articular disc, which acts as an obstacle to normal
      joint movement and results in clicking and popping sounds or locking and an
      inability to open the mouth widely. These conditions may be painless or they may
      be associated with pain, especially during function. The most common causes are
      trauma, which results in an immediate displacement of the disc, or chronic
      parafunction, which results in degenerative changes in the articular surfaces,
      increased friction, and gradual disc displacement.

PMID- 19591328
TI  - Temporomandibular joint reconstruction.
AB  - Temporomandibular joint (TMJ) reconstruction presents unique problems because of
      the integral and complex roles this joint plays in establishing and maintaining
      proper form and function of the stomatognathic system. The TMJ not only acts as a
      secondary growth center for the mandible in prepubescence, but it is also
      essential for the functions of mastication, speech, airway support, and
      deglutition in both the child and the adult.

PMID- 19591330
TI  - Coronectomy to prevent damage to the inferior alveolar nerve.
AB  - Conventional wisdom advises that when a tooth needs to be extracted, the whole
      tooth should be removed, usually with as little surrounding bone as possible.
      However, the evidence to support this is not compelling, and every dentist has
      experienced cases where the apices of teeth are not removed for a variety of
      reasons and, in most cases, the patient seems to suffer no ill effects. If one
      extrapolates from this, it is evident that there might be instances where it is
      actually preferable to leave the apical part of the root rather than remove it,
      and this can be carried out deliberately. The usual time that one would consider
      this is when the inferior alveolar nerve is intimately related to the roots of
      the lower molar teeth, and this occurs most often in relation to the third molar.
      This concept of deliberately removing only the crown and part of the root of the
      tooth is known variously as coronectomy, partial root removal, deliberate vital
      root retention, or partial odontectomy.

PMID- 19591329
TI  - Endoscopic surgery of the salivary glands.
AB  - Obstructive sialadenitis, with or without sialolithiasis, represents the most
      common inflammatory disorder of the major salivary glands, and sialolithiasis is
      one of the major causes of sialadenitis. Calculi in the salivary glands can be
      found in 1.2% of the general population. Other common causes of salivary gland
      obstruction are ductal strictures and kinks. The diagnosis of these problems has
      been traditionally hampered by the limitations of standard imaging techniques.
      Satisfactory management depends on the surgeon's ability to reach a precise
      anatomic diagnosis and to accurately locate the obstruction.

PMID- 19591331
TI  - Distraction osteogenesis in the treatment of dentofacial deformities.
AB  - Distraction osteogenesis (DO) is a major surgical technique that promotes new
      bone formation. It was first developed in the long bones and has now been applied
      to the facial bones. McCarthy et al. were the first to apply the procedure to the
      human mandible. The early uses in craniofacial surgery and orthognathic surgery
      were with extraoral appliances and therefore had limited appeal to many patients
      other than those with severe craniofacial anomalies, such as hemifacial
      microsomia. This changed with the introduction of intraoral appliances. Since
      that time, the use of DO has expanded to applications beyond those in jaw and
      craniofacial abnormalities to include its use in the treatment of cleft palate
      patients, condylar regeneration, discontinuity defects of the mandible, and for
      ridge augmentation before the placement of implants. Moreover, as experience in
      treating severe dentofacial deformities increased, surgeons were encouraged to
      intercede at an earlier age to minimize the extent of the deformity and to
      minimize relapse after surgery. This article describes some of the newer concepts
      in using DO to treat maxillary and mandibular deformities and growth
      discrepancies that are not amenable to routine orthognathic surgery.

PMID- 19591332
TI  - Surgical management of obstructive sleep apnea: changing the upper airway.
AB  - Obstructive sleep apnea is characterized by sleep deprivation and daytime fatigue
      and somnolence. It is conservatively estimated to occur in up to 3% of the adult
      population. However, the incidence is probably higher in industrialized
      countries, where sleep patterns are disrupted by abnormal work shifts. The
      incidence is also slightly higher in middle-aged males and may be as high as 67%
      in elderly males.

PMID- 19591333
TI  - Management of third molar-related nerve injuries: observe or treat?
AB  - Injury to branches of the trigeminal nerve is one of the possible complications
      associated with the removal of third molars. Fifty-two percent of patients
      referred to a university-based practice with trigeminal neurosensory complaints
      associated their nerve injury with third molar odontectomy. The inferior alveolar
      nerve (IAN) was the most commonly injured nerve (61.1%), followed by the lingual
      nerve (LN; 38.8%). There was a 1.5-times greater incidence in females, the mean
      age of the patients was 34.5 years, and the mean time to consultation from the
      third molar extraction date was 6.9 months. These data also showed that although
      the LN was the least commonly injured nerve, it was also the most likely to be
      severely damaged. It also showed that these patients were most likely to benefit
      from surgery. On the other hand, the IAN-injured patient often had less severe
      sensory impairment and therefore would not always benefit from surgical
      intervention. Therefore, the decision to observe or treat was generally based on
      which nerve is injured (LN or IAN), and this requires knowledge of the natural
      course of both LN and IAN recovery following injury, as well as the history of
      the injury; the physical findings; the results of the diagnostic procedures used
      to determine the degree of nerve injury; the characteristics of the neuropathic
      pain, if present; and the potential benefits and risks of surgery, if indicated.

PMID- 19591334
TI  - A randomized clinical study comparing the plaque inhibition effect of a SnF2/SHMP
      dentifrice (blend-a-med EXPERT GUMS PROTECTION) and a chlorhexidine digluconate
      dentifrice (Lacalut Aktiv).
AB  - OBJECTIVE: To compare the plaque inhibition benefits of a control 0.454% stannous
      fluoride/sodium hexametaphosphate/sodium fluoride dentifrice (SnF2/SHMP with 1450
      ppm F) to a chlorhexidine digluconate (0.05%), aluminum lactate (0.8%), and
      aluminum fluoride (AlF3/Chx with 1400 ppm F) dentifrice. METHODS: Twenty-nine
      subjects were randomized to a two-period, two-treatment, double-blind crossover
      sequence using blend-a-med EXPERT GUMS PROTECTION toothpaste (SnF2/SHMP) and
      Lacalut Aktiv toothpaste (AlF3/Chx). Each treatment was used along with a
      standard manual toothbrush (Oral-B P35 Indicator) for 17 days. Digital plaque
      image analysis (DPIA) was used at the end of each period for three consecutive
      days to evaluate plaque levels; a) overnight (A.M. pre-brush); b) following 40
      seconds of brushing with the test product (A.M. post-brush); and c) mid-afternoon
      (P.M.). Images were analyzed using an objective computer algorithm to calculate
      the total area of visible plaque. A four-day washout period was instituted for
      the crossover phase. RESULTS: Twenty-seven subjects completed the study. The
      SnF2/SHMP dentifrice provided a statistically significant lower level of plaque
      area coverage compared to the AlF3/Chx dentifrice at all time points. For the
      SnF2/SHMP dentifrice, plaque coverage was 19.4% lower (p = 0.0043) at the A.M.
      pre-brush, 25.6% lower (p = 0.0014) at the A.M. post-brush, and 19.8% lower (p =
      0.0057) at the P.M. measure relative to the AlF3/Chx dentifrice. CONCLUSION: The
      blend-a-med EXPERT GUMS PROTECTION toothpaste inhibits plaque regrowth, both
      overnight and during the day, to a significantly greater degree than Lacalut
      Aktiv. Additionally, immediately after brushing with blend-a-med EXPERT GUMS
      PROTECTION, subjects had significantly less plaque than after brushing with
      Lacalut Aktiv.

PMID- 19591335
TI  - Clinical investigation of the efficacy of a commercial mouthrinse containing
      0.05% cetylpyridinium chloride in reducing dental plaque.
AB  - OBJECTIVE: The objective of this independent, double-blind, seven-day clinical
      study was to assess the efficacy of a commercially available mouthrinse
      containing 0.05% CPC for controlling dental plaque relative to that of a control
      mouthrinse without 0.05% CPC. METHODS: Adult male and female subjects from the
      San Juan, Puerto Rico area reported to the clinical facility, having refrained
      from any oral hygiene procedures for 12 hours, and from eating, drinking, and
      smoking for four hours, for an assessment of the oral soft and hard tissues and a
      baseline dental plaque evaluation. Qualifying subjects were randomly assigned
      into one of the two treatment groups, and were provided with their assigned
      mouthrinse, an adult soft-bristled toothbrush, and a commercially available
      fluoride toothpaste for home use. Over the seven-day period of home use, during
      which there were no restrictions regarding diet or smoking habits, subjects were
      instructed to brush their teeth for one minute twice daily (morning and evening)
      with the toothbrush and toothpaste supplied, to rinse their mouths with water
      after brushing, and then to rinse with 15 ml of their assigned mouthrinse for one
      minute before expectorating. The use of other oral hygiene products or
      procedures, such as floss or interdental stimulators, was not permitted during
      the study. After seven days of product use, subjects returned to the clinical
      facility having followed the same restrictions with respect to oral hygiene
      procedures, eating, and drinking as prior to the baseline examination, and the
      oral soft and hard tissue assessments and dental plaque evaluations were
      repeated. Comparisons between treatment groups with respect to baseline-adjusted
      Plaque Index scores at the seven-day examination were performed using Analyses of
      Covariance, p < or = 0.05. RESULTS: Forty-eight subjects complied with the
      protocol and completed the study. Results demonstrated that, after seven days of
      product use and 12 hours after rinsing, both the CPC mouthrinse group and the
      control mouthrinse group exhibited statistically significant reductions in whole
      mouth Plaque Index scores (25.3% and 6.6%, respectively), in Plaque Index scores
      measured at interproximal sites (51.3% and 32.9%, respectively), and in Plaque
      Severity Index scores (43.5% and 25.4%, respectively). Relative to the control
      mouthrinse, the 0.05% CPC mouthrinse group exhibited statistically significant
      greater reductions in whole-mouth plaque scores (15.9%), in Plaque Index scores
      measured at interproximal sites (23%), and in Plaque Severity Index scores (17%).
      As the measurements were made 12 hours after final product use, the results also
      demonstrate that the CPC mouthrinse provides 12-hour protection against plaque
      accumulation in individuals with existing plaque. CONCLUSION: The overall results
      of this double-blind clinical study support the conclusion that after seven days
      of product use, a mouthrinse containing 0.05% CPC provides significantly greater
      efficacy for reducing dental plaque 12 hours after use, than does a control
      mouthrinse without 0.05% CPC.

PMID- 19591336
TI  - Laboratory assessment of the anticaries potential of a new dentifrice.
AB  - OBJECTIVE: The aim of the present study was to investigate the anticaries
      potential of a new sodium fluoride dentifrice in comparison to two commercial
      dentifrices containing different fluoride compounds by determining enamel
      fluoride uptake (EFU) and early caries lesion remineralization (REM) in an
      established in vitro caries remineralization/demineralization pH cycling model.
      METHODS: Test products were: new dentifrice formulation in a fluoride dose
      response (0; 675; 1426 ppm F as sodium fluoride [NaF-0; NaF-675; NaF]); Elmex
      Kariesschutz (1400 ppm F as amine fluoride [AmF]); and Oral-B Pro-Expert (1450
      ppm F-1100 ppm F as stannous fluoride and 350 ppm F as sodium fluoride [SnNaF]).
      Artificial caries-like lesions were formed in human enamel specimens by immersion
      in lactic acid buffer (LA). Specimens were then subjected to a daily cycling
      regime for 20 days comprising four one-minute dentifrice slurry treatments
      (prepared in pooled human saliva), and one four-hour LA challenge and
      remineralization in pooled human saliva. After 20 days, REM was evaluated as the
      change in surface Vickers microhardness from lesion baseline and EFU using the
      microdrill technique. The data were analyzed using ANOVA. RESULTS: A good
      fluoride dose-response was established for EFU and REM, with NaF delivering
      greater EFU and REM than NaF-675, which was superior to NaF-0 (p < 0.05). The new
      dentifrice NaF also showed greater EFU and REM than AmF and SnNaF (p < 0.05). In
      EFU, AmF and SnNaF were as efficacious as NaF-675 and superior to NaF-0 (p <
      0.05). AmF and NaF-675 were also comparable in REM, whereas both products
      exhibited superior REM vs. SnNaF (p < 0.05), which was superior to NaF-0 (p <
      0.05). CONCLUSION: The present study has demonstrated that fluoride dentifrices
      vary in their capability of enhancing anticaries potential as determined using an
      established in vitro caries cycling model. The new dentifrice NaF showed superior
      predicted anticaries potential compared to the two commercial dentifrices AmF and
      SnNaF in this model, which demonstrates the importance of fluoride compound and
      formulation excipients on driving anticaries potential in vitro.

PMID- 19591337
TI  - Clinical investigation of the efficacy of a commercial mouthrinse containing
      0.05% cetylpyridinium chloride in preventing dental plaque.
AB  - OBJECTIVE: The objective of this independent, double-blind, seven-day clinical
      study was to assess the efficacy of a commercially available mouthrinse
      containing 0.05% cetylpyridinium chloride (CPC) in preventing dental plaque build
      up relative to that of a control mouthrinse without 0.05% CPC. METHODS: Adult
      male and female subjects from the Sao Paulo, Brazil area reported to the clinical
      facility, having refrained from any oral hygiene procedures for 12 hours, and
      from eating, drinking, and smoking for four hours, for an assessment of the oral
      soft and hard tissues and a baseline dental plaque evaluation. Subjects
      qualifying for participation received a complete dental prophylaxis. Qualifying
      subjects were randomly assigned into one of the two treatment groups and were
      provided with their assigned mouthrinse, an adult soft-bristled toothbrush, and a
      commercially available fluoride toothpaste for home use. Over the seven-day
      period of home use, during which there were no restrictions regarding diet or
      smoking habits, subjects were instructed to brush their teeth for one minute
      twice daily (morning and evening) with the toothbrush and toothpaste supplied, to
      rinse their mouths with water after brushing, and then to rinse with 15 ml of
      their assigned mouthrinse for one minute before expectorating. The use of other
      oral hygiene products or procedures, such as floss or interdental stimulators,
      was not permitted during the study. After seven days of product use, subjects
      returned to the clinical facility having followed the same restrictions with
      respect to oral hygiene procedures, eating and drinking, as prior to the baseline
      examination, and the oral soft and hard tissue assessments and dental plaque
      evaluations were repeated. RESULTS: Forty-three subjects complied with the
      protocol and completed the study. Results demonstrated that after seven days of
      product use, mean plaque levels were statistically significantly lower (p < 0.05)
      than the pre-prophylaxis levels for both treatment groups. The mean plaque level
      for the CPC mouthrinse group was 46.1% of the pre-prophylaxis plaque level,
      whereas the mean plaque level for the control mouthrinse group was 75.5% of the
      pre-prophylaxis plaque level. The results demonstrate a statistically significant
      reduction in plaque build-up for the CPC mouthrinse group (29.3%) as compared to
      the control group. CONCLUSION: The overall results from this double-blind
      clinical study support the conclusion that, after seven days of product use, a
      mouthrinse containing 0.05% CPC provides significantly greater efficacy in
      preventing dental plaque build-up than a control mouthrinse without 0.05% CPC. As
      measurements were made 12 hours after final product use, the results also
      demonstrate that the CPC rinse provides 12-hour protection against dental plaque
      build-up.

PMID- 19591338
TI  - A clinical investigation of the efficacy of a commercial mouthrinse containing
      0.05% cetylpyridinium chloride to control established dental plaque and
      gingivitis.
AB  - OBJECTIVE: The objective of this independent, double-blind, parallel, six-week
      clinical study was to assess the efficacy of a commercially available mouthrinse
      containing 0.05% cetylpyridinium chloride (CPC) for controlling established
      dental plaque and gingivitis relative to that of a control mouthrinse without
      CPC. METHODS: Adult male and female subjects from the Maceio, Brazil area
      reported to the clinical facility, after having refrained from any oral hygiene
      procedures for 12 hours, and from eating, drinking, and smoking for four hours,
      for an assessment of the oral soft and hard tissues, and for a baseline
      gingivitis and dental plaque evaluation. Qualifying subjects were randomly
      assigned to one of the two treatment groups, and were provided with their
      assigned mouthrinse, and an adult soft-bristled toothbrush and toothpaste for
      home use. Over the six-week period of home use, during which there were no
      restrictions regarding diet or smoking habits, subjects were instructed to brush
      their teeth for one minute twice daily with the supplied toothbrush and a
      commercially available fluoride toothpaste, to rinse their mouths with water
      after brushing, and then to rinse with their assigned mouthrinse for one minute
      before expectorating. The use of any other oral hygiene products or procedures,
      such as floss or interdental stimulators, was not permitted during the study.
      After six weeks of product use, subjects returned to the clinical facility,
      having followed the same restrictions with respect to oral-hygiene procedures,
      eating and drinking, as with the baseline visit, and the oral soft and hard
      tissue assessments and gingivitis and dental plaque evaluations were repeated.
      RESULTS: One-hundred and ten subjects complied with the protocol and completed
      the study. With regard to supragingival plaque, after six weeks of product use,
      the subjects using the 0.05% CPC mouthrinse exhibited statistically significant
      reductions from baseline in whole-mouth Plaque Index scores (32.1%), in Plaque
      Index scores measured at interproximal sites (31.3%), and in Plaque Severity
      Index scores (84.8%). Subjects using the control mouthrinse exhibited
      statistically significant reductions from baseline in whole-mouth Plaque Index
      scores (7.0%), in Plaque Index scores measured at interproximal sites (6.4%), and
      in Plaque Severity Index scores (24.5%). When compared to the control mouthrinse
      group, the 0.05% CPC mouthrinse group presented statistically significant greater
      reductions in whole-mouth Plaque Index scores (27.9%), in Plaque Index scores
      measured at interproximal sites (27.9%), and in Plaque Severity Index scores
      (81.1%) after six weeks of product use. With regard to gingivitis, after six
      weeks of product use, subjects using the 0.05% CPC mouthrinse exhibited
      statistically significant reductions from baseline in whole-mouth Gingival Index
      scores (25.0%), in Gingival Index scores measured at interproximal sites (25.3%),
      and in Gingivitis Severity Index scores (42.4%). Subjects using the control
      mouthrinse exhibited statistically significant reductions from baseline in whole
      mouth Gingival Index scores (6.5%), in Gingival Index scores measured at
      interproximal sites (5.5%), and in Gingivitis Severity Index scores (11.6%). When
      compared to the control mouthrinse group, the 0.05% CPC mouthrinse group
      presented statistically significant greater reductions in whole-mouth Gingival
      Index scores (19.8%), in Gingival Index scores measured at interproximal sites
      (20.7%), and in Gingivitis Severity Index scores (35.5%) after six weeks of
      product use. CONCLUSION: The results of this double-blind, parallel, six-week
      clinical study support the conclusion that a mouthrinse containing 0.05% CPC is
      efficacious for controlling established dental plaque and gingivitis. As
      measurements were conducted 12 hours after product use, the results also
      demonstrate that the 0.5% CPC mouthrinse provides 12-hour protection against
      plaque and gingivitis.

PMID- 19591340
TI  - Clinical evaluation of the longevity and durability of an impressionless
      intraoral appliance (iNterra) system.
AB  - OBJECTIVE: To clinically evaluate the durability of an impressionless intraoral
      appliance (iNterra) system, fabricated using a direct/indirect technique.
      METHODS: Fifty-three (53) appliances were fabricated using the technique and
      followed for a median observation period of 301 days. Appliances were evaluated
      by calibrated operators for adaptation to teeth, retention, stability, and
      paresthesia, as reported by subjects, in addition to wear. RESULTS: All
      restorations (100%) were rated acceptable for adaptation to teeth, retention, and
      stability at placement. At the longest recalls, 96.2% of appliances survived
      without fracture. A similar percentage (96.0%) were rated acceptable for
      adaptation to teeth, retention, and stability. Paresthesia (reversible malodor)
      was reported in one (1.9%) case. In terms of wear, 98.1% of appliances delivered
      were rated as "no wear evident" or "evident but acceptable wear." CONCLUSION:
      Overall, the evaluators agreed that the impressionless system offered procedural
      efficiency advantages, was clinically viable, and should be a valuable option to
      practitioners considering appliance therapy to control parafunctional behavior.

PMID- 19591339
TI  - Comparison of a dentifrice containing 0.243% sodium fluoride, 0.3% triclosan, and
      2.0% copolymer in a silica base, and a dentifrice containing 0.243% sodium
      fluoride in a silica base: a three-year clinical trial of root caries and dental
      crowns among adults.
AB  - OBJECTIVE: Colgate Total toothpaste has been demonstrated to be highly effective
      in plaque and gingivitis control. The effect of triclosan on root caries and on
      the survival of dental crowns (fixed dental prosthetic treatment) has not been
      evaluated. In order to examine these important variables, a randomized controlled
      clinical trial was conducted comparing Colgate Total toothpaste with triclosan,
      and an identical fluoride toothpaste without triclosan. METHODS: Adult subjects
      were randomly assigned to a test group using Colgate Total plus Whitening
      toothpaste with triclosan, and a control group using Colgate sodium fluoride
      toothpaste without triclosan. By the end of the study, following three years of
      product use, an evaluation was performed to compare baseline data to the three
      year data for root caries and dental crown survival. Clinical root caries was
      evaluated by the Katz RCI- Root Caries Index. Within-treatment analysis for each
      dentifrice was conducted using a paired t-test. Between-treatment analysis was
      performed using Analysis of Covariance (ANCOVA). For fixed dental prosthetic
      treatment evaluation, dental crowns were dichotomized for success and failure at
      the end of the study. Within-treatment analysis for each dentifrice was conducted
      using a paired t-test. Between-treatment analysis was performed using the
      Bonferroni test. RESULTS: One-thousand, three-hundred, and fifty-seven subjects
      (1,357) completed the study. Regarding root caries, at termination of the study
      the Colgate Total group presented a mean score of 1.14 +/- 1.75 and a +5.6%
      change from baseline, while the sodium fluoride toothpaste presented a mean of
      1.25 +/- 1.88 and a +43.2% change from baseline (p < 0.001). The adjusted mean
      root caries increment was 0.07 +/- 0.03 for the Colgate Total group, and 0.38 +/-
      0.03 for the sodium fluoride toothpaste group (p < 0.001). Regarding crowns, at
      termination of the study the Colgate Total group presented a mean score of 5.38
      +/- 3.70 and a +1.1% change from baseline, while the sodium fluoride toothpaste
      without triclosan presented a mean of 5.75 +/- 3.86 and a +3.8% change from
      baseline (p < 0.001). The mean (adjusted for multiple comparisons) dental crowns
      failure increment was 0.09 +/- 0.03 for the Colgate Total group, and 0.31 +/-
      0.02 for the sodium fluoride toothpaste group (p < 0.001). CONCLUSION: A
      comparison between the two study groups revealed a statistically significant
      difference for root caries and dental crown failure scores, both favoring the
      triclosan toothpaste (Colgate Total). The significantly lower root caries and
      observed dental crown failure scores among the Colgate Total toothpaste users
      indicate an effect of the triclosan and the copolymer system. These results are
      important and could provide a strong and valuable public health measure.

PMID- 19591342
TI  - [Clopidogrel plus proton pump inhibitor: is infarct risk increased? (interview by
      Dr. Thomas Meissner)].

PMID- 19591341
TI  - [Enlarged lymph nodes, fever, abdominal cramps, numbness in arm and leg. Deciding
      evidence in the gluteal fold].

PMID- 19591343
TI  - [In reimbursement billing for case consultations do you remember letters, copies,
      telephone, etc.? Even small livestock produces dung].

PMID- 19591344
TI  - [Child welfare and new media--the computer is my best friend].

PMID- 19591345
TI  - [Food allergies and irritable bowel syndrome. Evaluating the causes].

PMID- 19591346
TI  - [Physicians, allied professions and patients in one boat in the near future:
      collaborative national strategy for diabetic patients].

PMID- 19591347
TI  - [Observations on cupping. High toxin concentration in blood from cupping].

PMID- 19591348
TI  - [Close to the patient. Listen, look closely, touch!].

PMID- 19591349
TI  - [Tongue and pharynx: "Please open wide..."].

PMID- 19591350
TI  - [Ear and nose: an aid to diagnosis for the general practitioner].

PMID- 19591351
TI  - [How to do the rectal exam].

PMID- 19591352
TI  - [Inspection, palpation and ultrasound--the basics for clinical examination of the
      scrotum and testes].

PMID- 19591353
TI  - [Hypertension and diastolic dysfunction].

PMID- 19591354
TI  - [Pneumococcal pneumonia. Effective prevention of invasive course of illness].

PMID- 19591355
TI  - [Welcome side effect of vaccination. Effective for the lung and also helps the
      heart].

PMID- 19591356
TI  - [Tropical diseases. How to deal with in the general practitioner's office].

PMID- 19591358
TI  - An impossible task: summing up the value of a nurse.

PMID- 19591357
TI  - [Once daily therapy of erectile dysfunction. "Flexible love life without time
      constraints"].

PMID- 19591359
TI  - Pain: as varied as the populations we treat.

PMID- 19591360
TI  - Nurse's assessment of caregiver burden.
AB  - Caregivers of an older adult family member with dementia face many negative
      physical and mental health consequences, as well as financial impact. Caregiver
      burden and depressive symptoms are defined and factors that affect caregiver
      burden are examined. Tips for nurse assessment of caregiver depressive symptoms
      also are included.

PMID- 19591361
TI  - Evidence-based practice, clinical simulations workshop, and intravenous
      medications: moving toward safer practice.
AB  - In an era of increased emphasis on medication safety practice, a gap exists in
      the translation of research to clinical practice for administering intravenous
      continuous infusion medications. An educational initiative was designed for
      medical-surgical nurses in a tertiary care center to standardize operational
      procedures in a clinical model focusing on evidence-based practice.

PMID- 19591362
TI  - Pain experience in hospitalized adults with sickle cell disease.
AB  - Adult patients with sickle cell disease often report high pain intensity ratings
      during hospitalization. However, no evidence of upward titration in analgesics
      was found particularly during prolonged episodes. Development of algorithms to
      facilitate decisions regarding titration of medications is recommended.

PMID- 19591363
TI  - Continuity of care in ambulatory surgery critical pathways: the patients'
      perceptions.
AB  - This study dealt with patients' experiences of the continuity of care through an
      ambulatory surgical critical pathway. Data were collected from theme interviews
      conducted with surgical patients 25 days after their procedures. Important
      factors in continuity of care were defined as time flow, coordination flow,
      caring relationship flow, and information flow.

PMID- 19591364
TI  - Treatment-related fatigue and exercise in patients with cancer: a systematic
      review.
AB  - PURPOSE: The purpose of this systematic review was to determine if patients
      receiving treatment for cancer experienced less treatment-related fatigue if they
      participated in a regular committed exercise regimen, compared to those who did
      not exercise regularly. RESEARCH QUESTION: What is the relationship between
      treatment-related fatigue and exercise during chemotherapy and/or radiation?
      METHOD: A systematic review of 19 English-language studies from the United
      States, Europe, and Australia, conducted between January 2000 and October 2006,
      investigating the effect of exercise on chemotherapy and/or radiation-related
      fatigue was completed. Included in the review were randomized controlled trials,
      pilot studies, and secondary analysis of previously reported studies such as
      systematic reviews. Ten studies that fit the preestablished criteria were
      retained for the review. The Priority Symptom Management (PRISM) system developed
      by the Oncology Nursing Society was used for leveling evidence. FINDINGS: Eight
      of the ten studies showed regular committed exercise resulted in less fatigue
      among the experimental group participating in exercise programs. A limitation
      common to the studies included in this review was the lack of a universal
      definition for fatigue, and therefore, the lack of a universal measuring
      instrument to evaluate the effectiveness of interventions. CONCLUSIONS: There is
      evidence to include an individualized exercise program for patients on
      chemotherapy and/or radiation therapy. Studies showed no adverse effects of
      exercise such as increased fatigue or falls.

PMID- 19591365
TI  - Systematic reviews.

PMID- 19591366
TI  - Nurses nurturing nurses: outcomes and lessons learned.
AB  - Retention of new graduate nurses is a challenge for acute care agencies. The
      Academy of Medical-Surgical Nurses sponsored a hospital-based formal mentorship
      program, Nurses Nurturing Nurses, for interested agencies. The outcomes and
      lessons learned from this project are presented.

PMID- 19591368
TI  - Leukemia.

PMID- 19591367
TI  - An Army nurse in Korea: why cultural awareness is important caring for patients.

PMID- 19591369
TI  - Practical use of the nursing Code of Ethics: part II.
AB  - The Code Provisions V through IX focus on a variety of responsibilities for the
      professional nurse. Provision V spotlights nurses' obligation to the same values
      and actions for themselves as are espoused in The Code for their patients.
      Provision VI addresses the responsibility of all nurses to maintain quality
      patient care, regardless of their roles in the health care system. Meeting
      professional obligations to maintain and forward the nursing profession can take
      a variety of forms, as indicated in Provision VII. Provision VIII reviews the
      macro level of professional nursing responsibility by centering on the issues of
      world hunger, pollution, and other violations of justice. Finally, Provision IX
      identifies the importance of involvement in professional associations and their
      efforts for social reform. The first two provisions of The Code address the
      boundaries of obligation and dependability (Lachman, 2009), and the last three
      address the duties outside individual patient experience.

PMID- 19591370
TI  - Assessing family preferences for participation in care in hospitalized older
      adults.

PMID- 19591371
TI  - Power dynamics, health policy, and politics.

PMID- 19591372
TI  - Leadership: social identity and guiding from within.
AB  - An important field in leadership research is that of the social identity of the
      group and what that means for leadership. In health care, there are many
      different types of social identities that vary by hospital, geography, and
      profession. Leaders often sabotage their effectiveness when they do not consider
      the social values of the group. The work of leaders is to help move units and
      organizations to a higher level of performance. Identifying the social identity
      of the group is the first step. The most successful have expertise in assessing
      the social identity of groups and developing a commonality of a shared vision
      that represents the best work of the group and of the leader.

PMID- 19591373
TI  - Cannabinoids and atherosclerosis.
AB  - The endocannabinoids are a family of lipid neurotransmitters that engage the same
      membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde
      signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous
      cannabinoids and studies of the physiological functions of the cannabinoid system
      in the brain and body are producing a number of important findings about the role
      of membrane lipids and fatty acids. The role of lipid membranes in the
      cannabinoid system follows from the fact that the source and supply of endogenous
      cannabinoids are derived from arachidonic acid. The study of molecules which
      influence the cannabinoid system in the brain and body is crucial in search of
      medical preparations with the therapeutic effects of the phytocannabinoids
      without the negative effects on cognitive function attributed to cannabis. Basic
      information about function and role of the endocannabinoid system is summarized
      in the paper; possible therapeutic action of cannabinoids, effects on
      atherosclerosis specially, is described at the close.

PMID- 19591374
TI  - Pathophysiology of preterm labour.
AB  - A specific pathogenic process of premature delivery represents the inflammation.
      Birth canal infections seem to play a key role in the ethiopathogenesis of
      premature delivery; the related biochemical changes significantly affect
      perinatal morbidity and mortality. Other potential causes, particularly hormone
      metabolism disorders or uteroplacental ischaemia have been intensively studied.
      This process is related both to the mother and fetus. Fetal inflammatory response
      (FIRS)--can occur without maternal response--and it is related to a significant
      increase in perinatal morbidity. FIRS has definite laboratory, histological and
      clinical criteria. Effective primary prevention of premature delivery does not
      exist at present. The sensitivity and specificity of so far used laboratory
      markers is low. Thus, the research is focused on finding new inflammation markers
      allowing the early identification of pregnant women at a high risk of premature
      delivery and fetal inflammation. The screening of women at a high risk by means
      of new laboratory and ultrasound tests belongs to the most important steps in
      secondary and tertiary prevention of premature delivery. Intensive research of
      potential trigger mechanisms has been carried out, including a variety of gene
      types, which are potentially related to the process of premature delivery.

PMID- 19591375
TI  - Somatic and endocrinological changes in non medicated ADHD children.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most commonly
      diagnosed childhood psychiatric disorders and it constitutes a group of
      developmental disorders, which are characterized by inadequate level of
      attention, excessive activity and impulsivity. In connection with neurological
      and endocrinological changes, children with ADHD can show also changes in the
      growth and development without consequence to the medication. Differences were
      found especially in higher weight and BMI. Very few studies were done on this
      topic and the results of the studies are very different, methods are
      heterogeneous and insufficient. The most serious absence is the much reduced
      number of anthropometrics and other characteristics and parameters. Studies
      usually analyse only BMI, height and weight and do not take into account socio
      economic characteristics, feeding customs and other important factors. Many
      studies are done on changes in growth only associated with medical treatment of
      children ADHD. However changes in the development and growth can be a
      manifestation of the disorder itself. Authors of this paper review studies which
      monitor changes in the development of children with ADHD and compare their
      results.

PMID- 19591376
TI  - The biological environment of Hodgkin's lymphoma and the role of the chemokine
      CCL17/TARC.
AB  - Hodgkin's lymphoma is a lymphoproliferative disease, which differs in its
      morphology and therapeutic response from other lymphomas. Neoplastic cells
      represent only a minor cell population of the tumour, while the major part of the
      tumour is formed by inflammatory cells. It results from the production of
      cytokines and chemokines both by neoplastic cells and by inflammatory cells. An
      important prognostic marker in Hodgkin's lymphoma appears to be the chemokine (C
      C motif) ligand 17 (CCL17), also known as thymus and activation-related chemokine
      (TARC). This chemokine is expressed by many cell types and tissues, and in the
      case of Hodgkin lymphoma, also by Reed-Sternberg cells. CCL17/TARC binds to
      chemokine receptors CCR4 and CCR8 and displays chemotactic activity for T
      lymphocytes and some other leukocytes. The understanding of biological pathways
      in Hodgkin's lymphoma could be important for monitoring of disease activity and
      for the development of future targeted therapy.

PMID- 19591377
TI  - Can the preoperative value of VLPP and MUCP predict the postoperative quality of
      life?
AB  - OBJECTIVE: The aim of this study was to determine whether low values of VLPP
      (Valsava Leak Point Pressure) and low values of MUCP (Maximal Urethral Closure
      Pressure) before operation can predict quality of life (QOL) after anti
      incontinence surgery. METHODS: 72 stress incontinent women were included in this
      study. All women underwent anti-incontinent surgery. We compared the quality of
      life using I-QOL (Incontinence Quality of Life) assessment with parameters of
      urodynamic measurement VLPP and MUCP The women filled in an I-QOL questionnaire
      before surgery and three month afterwards. RESULTS: As in other studies, low
      preoperative value of the VLPP < or =60 cmH2O was not related to a statistically
      lower quality of life (average I-QOL for VLPP < or =60 cmH2O was 38.4 and 48.9
      for VLPP > 60 cmH2O). We did not find statistically significant lower quality of
      life in women with MUCP < or =20 cmH2O (average I-QOL 38.2, and for MUCP > 20
      39.7). The quality of life was significantly changed after successful anti
      incontinent operation, but independently of the preoperative value of VLPP or
      MUCP, average I-QOL for VLPP < or =60 cmH2O was 81.5 and 82.8 for VLPP > 60
      cmH20, for MUCP < or =20 cmH2O 79.5, and 86.4 for MUCP >20. CONCLUSIONS: Low
      preoperative values of MUCP and VLPP did not correlate with QOL. Preoperative
      VLPP and MUCP do not predict the QOL after anti-incontinent surgery.

PMID- 19591379
TI  - The sentence intelligibility in different types of noise regarding people with a
      normal hearing ability.
AB  - The capability of speech understanding can be tested in the form of sentences.
      This report describes the origin of a new test in the Czech language to evaluate
      the sentence intelligibility with the presence of the competitive disturb noise.
      The results of the test depend on the test project, sentence material,
      competitive signal, test evaluation, and hearing conditions. Pilot results were
      obtained from 3 different noises (Speech noise, Babble noise, Cocktail party
      noise) at 16 people with a normal hearing ability. The Speech noise, which is
      recommended by a technical standard, mask sentences very poorly. On the other
      hand, the Babble noise and the Cocktail party noise, which are used to mask
      sentences in different languages, mask at lower intensities.

PMID- 19591378
TI  - Thrombophilia and pulmonary endarterectomy.
AB  - In the present study, we compared groups of patients with and without
      thrombophilia, who underwent pulmonary endarterectomy (PEA), definitive treatment
      for chronic pulmonary hypertension resulting from thromboembolic disease. METHODS
      AND PATIENTS: Between September 2004 and June 2007, we operated 54 patients with
      CTEPH. We divided our patients into three groups. Group I patients, had one or
      more signs of serious thrombophilia (15 patients), Group II patients, had no
      signs of thrombophilia (23 patients without thrombophilia and without
      Methylenetetrahydrofolate Reductase (MTHFR)), and Group III patients with MTHFR
      (16 patients with MTHFR only, without any serious thrombophilia). RESULTS: After
      the surgery, there was a statistically considerable improvement of hemodynamic
      parameters (mPA, CI, PVR) in all groups, without a statistical difference between
      the groups. Comparison of all these groups showed more complications in-group I
      (thrombophilia), in particular reperfusion oedema, pericardial effusion, and
      renal insufficiency. Within one month, there was a considerable improvement or
      normalisation of haemodynamic parameters, an increase in walking distance at the
      six-minute walking test, and NYHA classification with no significant difference
      between the three groups. CONCLUSIONS: Early hemodynamic results of patients with
      thrombophilia after PEA, were comparable to the results of patients without
      thrombophilia, when we looked at both clinical and hemodynamic improvements. We
      did not find any differences when we looked at the results between Group II and
      Group III (MTHF), when we considered the number and type of complications.
      Patients with thrombophilia in Group I had statistically higher morbidity,
      especially when it came to a higher number of reperfusion oedema, pericardial
      effusion, and renal insufficiency.

PMID- 19591380
TI  - Impact of prenatal and acute methamphetamine exposure on behaviour of adult male
      rats.
AB  - Psychostimulants have been shown to alter behaviour in both rats and humans. The
      aim of the present study was: (1) to assess the effect of prenatal and acute
      methamphetamine (MA) administration on behaviour in adult male rats and (2) to
      find out if the prenatal exposure to MA increases sensitivity to acute MA
      application in adulthood. Behaviour of adult male rats prenatally exposed to MA
      (5 mg/kg) or no drug was tested in Open field (OF) and Elevated plus maze (EPM).
      Half of the animals were injected with MA (1 mg/kg) subcutaneously 30 minutes
      prior to testing. Locomotion, exploration, comforting behaviour and anxiety were
      evaluated in the OF, while anxiety and exploratory behaviour were assessed in the
      EPM. Our results showed that prenatal MA did not have an effect on baseline
      behaviour in either of the tests. By contrast, acute MA increased overall
      psychomotor activity by increasing locomotion and exploratory behaviour and
      decreasing comforting behaviour. Moreover, adult rats prenatally exposed to MA
      were more sensitive to the effects of acute MA on exploration. In addition, acute
      MA application decreased anxiety in the OF as well as in the EPM. Our present
      study, thus, demonstrates that acute MA increases overall psychomotor activity
      and decreases anxiety to novel environment. To further support our hypothesis
      that prenatal MA exposure increases sensitivity to drugs in adulthood, studies
      investigating the levels of dopamine in the rat brain after prenatal MA exposure
      are planned.

PMID- 19591381
TI  - Individual replacement of the frontal bone defect: case report.
AB  - The objective of the skeletal defects reconstruction using individual implants is
      an attempt to replace lost and damaged anatomical bone structures, renew their
      original function, and at the same time, to restore the original aesthetic visual
      aspect. This work is focused on a demonstration of the design methods,
      fabrication and surgical techniques of the custom-made replacement of a large
      defect of the frontal bone on the skull. The patient was a 30-year-old woman with
      a defect of the frontal bone in the size of 7 x 3 x 2 cm after a serious
      polytrauma. The size and character of the defect excluded the use of commonly
      supplied augmentations. The geometry of the individual replacement was designed
      on the basis of a 3D model of the defect obtained from a series of CT scans.
      After verification of the shape accuracy of the defect made from plastic on a 3D
      printer, the individual replacement was fabricated from an ultra high molecular
      weight polyethylene (UHMWPE) by machining with the use of the CNC technology. The
      success of the augmentation depends on the accurate and precise fabrication of
      the individual replacement, which is highly demanding on the used advanced
      technologies.

PMID- 19591382
TI  - Prenatal diagnosis of pentalogy of Cantrell in the third trimester.
AB  - We report about the prenatal diagnosis of pentalogy of Cantrell in the third
      trimester. In this case sonographic evaluation revealed mild form of ectopia
      cordis, severe omphalocele, small meningomyelocele, mild hydrocephalus, severe
      polyhydramnios and allantoic cyst of the umbilical cord. The pregnancy was
      terminated by a caesarean section at 35 weeks of pregnancy because of severe
      polyhydramnios. The neonate died shortly after delivery and the obduction
      confirmed the diagnosis of pentalogy of Cantrell. We discuss the reason of the
      late prenatal diagnosis in this case, the importance of early prenatal diagnosis
      and the options of pregnancy management.

PMID- 19591383
TI  - Retrospective diagnosis.

PMID- 19591384
TI  - Palaeopathological diagnosis after 2500 years. The case of Imakhetkherresnet,
      sister of priest Iufaa.
AB  - The aim of palaeopathological studies has been traditionally the determination of
      a diagnosis of any found pathological change. If based merely on skeletal
      evidence, most of them proved to be only tentative. Our case of the mature female
      Imakhetkherresnet, sister of the lector-priest Iufaa, having preserved scraps of
      soft tissue, enabled a precise diagnosis. Her skeletized mummy was discovered in
      Iufaa's unmolested tomb dating late 26th Dynasty at Abusir (Egypt) by the Czech
      Institute of Egyptology in 2001. A large smooth-walled cavity moulded by pressure
      of a relatively hard, globular and lobulated tissue mass was found inside the
      sacrum, growing in hour-glass shape outside it. By macroscopic and radiographic
      examination its diagnosis was suggested, while by histological analysis with
      histochemical tests and comparison with a recent case, the origin of the hollow
      could be "clinically" determined. It was caused by a benign tumour, originating
      in the nerve sheath, called neurilemmoma (schwannoma, neurinoma). This kind of
      tumour, occurring in the sacrum relatively rarely, was never before described in
      the palaeopathological literature.

PMID- 19591385
TI  - Children's cranial lesions from Neolithic.
AB  - In skeletal material from the neolithic settlement at Makotrasy, county Kladno,
      were analysed two children's craniums (identification numbers Ao 8218 and Ao
      4184) with pathological cases. Case 1 (Object 127, Ao 8218) is the individual
      about 4 to 5 years old. There is oval aperture with the diameter 25 x 20 mm in
      the area of anthropometrical point bregma, with vertical, multiple knurled edges.
      Bevelled and rounded segment in the left frontal part of the aperture with
      diameter 10 mm is imitating healing process. We suggest this case is the
      trephination with the marks of the healing process in the period of 1 to 2 weeks
      after the surgery took over. Case 2 (Pit 25, Ao 4184) is child with age
      determined about 4 years old. Cranium was found buried separately. There is oval
      defect located at os occipitale and os parietale sin and goes through sutura
      lambdoidea. Caudal part of defect is missing. The edge of the defect is sharp and
      inward bevelled with exposed diploe. Traces of any vital reaction were not
      identified. Diameter is around 50 mm. Perimortal trephination leading to death,
      or postmortal taking of the trephinational amulet must be considered. There were
      several pathological lesions on the same skull. Defect of oval shape sized 8 x 12
      mm is located at the os parietale dex. Defect interferes mostly with lamina
      externa and less with lamina interna. Exposed diploe is without any vital
      reaction.

PMID- 19591386
TI  - Diagnostics in late medieval sources.
AB  - In this paper I focus on the nature of diagnosis in the Czech written medical
      sources. In the first part, the character of medieval medicine is described.
      Further, I deal with contemporary definitions of disease and some important
      aspects of diagnostic; finally, I adduce the signs of diseases described in
      examined sources: primarily the manuscript texts created in the first half of the
      15th century and old printed books from the 16th century. I come to conclusion,
      that the medieval medicine was oriented on health problems instead of concrete
      diseases. For non-university trained physicians, the methods of healing were more
      important than quest to find the concrete disease.

PMID- 19591387
TI  - Diagnosis of miracle or miraculous diagnosis? Comments on early modern
      understanding of unnaturalness.
AB  - The paper deals with certain aspects of healing miracles in the 17th century. In
      the beginning I outline methods recently developed in the history of medicine to
      deal with unnatural phenomena. I use division suggested by Anne-Marie Korte and
      comment on sceptical, apologetical and hermeneutical approach. Further I
      demonstrate difficulties which we face in study of miracles on two specific
      cases: Our Lady of Foy, and (missing) burning scars of injured brewers. In the
      end I describe perhaps the most specific contemporary definition of "miraculous"
      which stemmed from tradition of forensic medicine. For this purpose I use a
      treaties of Johannes Franciscus Low ab Erlsfeld, professor of Prague Medical
      Faculty in the beginning of the 18th century which follow work of famous papal
      physician of the previous century Paolo Zacchia.

PMID- 19591388
TI  - Retrospective diagnosis: use and abuse in medical historiography.
AB  - Medical papers on diseases of famous persons, sometimes called pathographies,
      constitute the by far largest section of publications dealing with historical
      diagnosis. The procedure of attaching modern diagnostic labels to illustrious
      personalities of the past, i.e. retrospective diagnosis, has stimulated an
      ongoing theoretical debate among clinicians and medical historians. The purpose
      of this paper is to clarify some of the issues involved. Key problems of
      retrospective diagnostics are reviewed and analysed. In addition, the case
      history of the Polish composer Fryderyk Chopin is used to highlight problems and
      pitfalls of this method. Whereas contemporary physicians are used to apply
      present-day nosological categories to individuals of the past or historical
      epidemics, medical historians are more cautious to do so. They argue that in the
      absence of definite proofs retrospective diagnoses often are nothing more than
      mere speculation. Another important counter-argument is that medical knowledge
      itself varies over time and historical changes in nosology must not be ignored.
      Future pathographies should use primary sources extensively, focus on historical
      context and minimize the pursuit of retrospective diagnoses or causes of death.
      Only with a fundamentally revised method, a more critical approach to
      retrospective diagnostics, and far more serious objectives will medical
      biographies be in a position to break new ground.

PMID- 19591389
TI  - Reporting death. The case of Austrian tuberculosis mortality registration-
      critique and consequences for historical epidemiology.
AB  - The purpose of this article is to introduce recent insights into methodological
      problems of medical diagnosis in history, historical denotations, and
      interpretation of historical disease nomenclature (causes of death) in the 19th
      century related to tuberculosis mortality in Austria. Comparing and discussing
      the main sources--church death records, death certificates and compiled
      statistics on the causes of death--the paper illustrates practices of
      documentation and their impact on the quality of the compiled data. As a
      consequence of the insufficient quality observed, the article argues that
      historical epidemiology has to be careful when comparing national statistics on
      the causes of death and that it is necessary to consider the different contexts
      of the sources' origin. The paper is divided into three sections: it begins with
      a brief introduction into the history of tuberculosis mortality in the late 19th
      century and the recent discussions on the problems of historical diagnosis in
      historiography. The second section gives an overview of registration practice,
      the different types of sources and describes their specific context of origin. By
      focusing on the terms Abzehrung/Auszehrung and discussing the practice of
      assignment, the third part demonstrates that in case of tuberculosis, mortality
      rates have been overestimated for the time up to 1900. Finally the article gives
      two examples to exemplify further problems, evoked by the change in registration
      of causes of death in 1873 and 1896. The paper concludes with a summary of the
      results and consequences for medical and demographic history.

PMID- 19591390
TI  - History of diagnostics in dermatovenerology on Medical Faculty in Prague.
AB  - The article deals with the history of diagnostics in dermatovenerology on Medical
      Faculty in Prague from 1875 to 1910. Medical Reports of General Hospital in
      Prague from those years were used as the source of data. Three dermatologic and
      venereal diagnoses from years 1875, 1881, 1885, 1890, 1895, 1899, 1906 and 1910
      were used for a statistic comparison. The article also contains short description
      of institutional background of dermatovenerology in Prague during this period.

PMID- 19591391
TI  - Epidemiological studies of lung carcinoma incidence in uranium miners
      (accumulation and retrospective use of diagnostic data).
AB  - The paper attracts attention to the question of accumulation and retrospective
      use of diagnostic data in the early epidemiological studies of lung carcinoma
      incidence in uranium miners in Schneeberg, Saxony, and in Jachymov
      (Joachimsthal), Bohemia.

PMID- 19591392
TI  - [Distracter effect on the right angle perception].
AB  - On the monitor three light spots form imaginary sides of the right angle. The
      perceived angle distortions arose when distracting stripes were flanking each
      stimulus spot and subjects were asked to readjust the orthogonal orientation of
      the sides. The dependence of the subject's error value on the spot-to-stripe
      distance was measured. The data obtained was referred to a certain lateral
      interaction processes which manifested themselves as a local information
      averaging concerned with the positions of the stimulus parts. The quantitative
      parameters of the lateral interaction were established by a simplified
      mathematical model based on the conception of the centroid biases which are due
      to summation of the corresponding patterns of excitations in the visual pathways.
      A good agreement between the computational and experimental data was obtained.

PMID- 19591393
TI  - [Interhemispheric asymmetry of the auditory evoked potentials and mismatch
      negativities during sound source localization].
AB  - The long-latency auditory evoked potentials and mismatch negativities were
      studied in humans using dichotic stimulation. Deviant stimuli either changed
      their azimuth abruptly from zero to +/- 22.5 degrees or moved gradually to the
      left/right from the head midline at different velocities ranging from 11.25
      degrees per second to 112.5 degrees per second. It was demonstrated that the
      amplitude of N1-P2 wave of the evoked potential was higher when recorded from the
      right frontal sites than from the left sites. The mismatch negativity depended
      significantly on the spatial location of the deviant stimulus: the right deviants
      elicited greater and earlier mismatch negativities than the left deviants. The
      involvement of the right hemisphere in the auditory spatial discrimination is
      discussed.

PMID- 19591394
TI  - [EEG frequency-amplitude characteristics of successful recognition of emotions in
      speech].
AB  - Psychophysiological mechanisms of perception of speech emotional expression were
      studied. Comparison of EEG between 2 extreme groups (with high and low indexes
      of) identification of emotional intonation) revealed significant differences in
      frequency-amplitude characteristics of brain electrical activity. Two general
      conclusions can be made from the data obtained. Firstly, the subjects with low
      identification rates show a higher brain activation and reactivity both during
      the emotion identification task and at rest as compared to the subjects with high
      identification rates. Secondly, the data reveal specific activation within the
      right posterior temporal cortex. Therefore, high initial cortical activation and
      more pronounced EEG reactivity impede recognition of emotion in speech.

PMID- 19591395
TI  - [Corticospinal influence on the hand distal muscles under weight load].
AB  - Baseline and synchronous evoked EMG activity were studied in wrist muscles of
      human subjects under conditions of transcranial magnetic stimulation of the motor
      cortex during the performance of different motor tasks. During recording, a
      subject had to hold a loaded handle with the thumb and index finger. When a
      subject increased the grip force (intentionally or under conditions of increasing
      handle load), the synchronous EMG response increased proportionally to the muscle
      activity. If the subject moved the hand with the handle up and down with the
      amplitude of 10 cm and frequency of 0.5-1.0 Hz, the grip force changed in
      accordance with the expected inertia load. The EMG response in the abductor
      pollicis brevis increased to a larger degree than the baseline activity. In case
      of a grip force increase in response to a sudden unexpected rise of the inertia
      load, the evoked EMG response increased to a lesser degree than the muscle
      baseline activity. The results suggest that the increase in the evoked response
      during voluntary periodical movement of the handle is related to the anticipatory
      grip force adjustment. The involvement of the motor cortex in the anticipatory
      activity of distal muscles is discussed.

PMID- 19591396
TI  - [Visual analog of mismatch negativity when stimuli differ in the duration].
AB  - Event-related potentials (ERPs) were studied in 10 practically healthy volunteers
      (6 male, 4 female) aged from 18 to 24 years during presentation of rare deviant
      and frequent standard visual stimuli in a standard odd-ball paradigm under
      conditions of active attention and inattention to stimulus duration. The
      deviation of the duration of deviant stimuli (50, 100 and 150 ms) from that of
      the standard stimuli (200 ms) varied from 50 to 150 ms. In series where
      deviations were 100 and 150 ms, a negative difference wave with the latency of
      200-400 ms was revealed (ERP to the deviant stimulus under conditions of
      inattention minus ERP to the control stimulus of the same duration) mainly in the
      right temporal region. Since this difference negative wave appeared under
      conditions of inattention, we suppose that this wave is the visual analogue of
      mismatch negativity (MMN) and related to automatic detection of deviation of
      stimulus duration.

PMID- 19591397
TI  - [Decrease in N170 evoked potential component latency during repeated presentation
      of face images].
AB  - The 15 healthy volunteers EEG from 28 channels was recorded during the
      presentation of visual stimuli in the form of face and building images. The
      stimuli were presented in two series. The first series consisted of 60 face and
      60 building images presented in random order. The second series consisted of 30
      face and 30 building images. The second series began 1.5-2 min after the end of
      the first ore. No instruction was given to the participants. P1, N170 and VPP EP
      components were identified for both stimuli categories. These components were
      located in the medial parietal area (Brodmann area 40). P1 and N170 components
      were recorded in the superior temporal fissure (Brodmann area 21, STS region),
      the first component had the latency 120 ms, the second one--155 ms. VPP was
      recorded with the latency 190 ms (Brodmann area 19). Dynamic mapping of EP
      components with the latency from 97 to 242 ms revealed the removal of positive
      maximums from occipital to frontal areas through temporal ones and their
      subsequent returning to occipital areas through the central ones. During the
      comparison of EP components to face and building images the amplitude differences
      were revealed in the following areas: P1--in frontal, central and anterior
      temporal areas, N170--in frontal, central, temporal and parietal areas, VPP--in
      all areas. It was also revealed that N170 latency was 12 ms shorter for face than
      for building images. It was proposed that the above mentioned N170 latency
      decrease for face in comparison with building images is connected with the
      different space location of the fusiform area responsible for face and building
      images recognition. Priming--the effect that is revealed during the repetitive
      face images presentation is interpreted as the manifestation of functional
      heterogeneity of the fusiform area responsible for the face images recognition.
      The hypothesis is put forward that the parts of extrastriate cortex which are
      located closer to the central retinotopical projections can take part not only in
      the recognition process but also in memory traces fixation with the peripheral
      parts of these areas being responsible for the stimuli presented for the fist
      time.

PMID- 19591398
TI  - [Crossbills (Loxia curvirostra) are able to form concept "larger than"].
AB  - A new original method to investigate some cognitive abilities of wild passerine
      birds was developed. In the course of experiments with five crossbills (Loxia
      curvirostra), it was shown that the method can be used to evaluate the ability of
      birds to form concepts. Crossbills were presented with pairs of stimuli each
      consisting of 1 to 10 equal elements. All the five crossbills learned to choose,
      within a pair, a stimulus with a larger array of elements. The birds successfully
      transferred this performance to novel stimuli considerably different from the
      training pairs comparable with the latter only in the number or area. One of the
      birds showed a complete transfer of the acquired performance of choice to stimuli
      consisting of 10 to 20 equal elements. Thus, the ability of forest passerine
      birds to form concept "larger than" was shown.

PMID- 19591399
TI  - [Influence of vibrissectomy in early postnatal ontogeny of rat pups on behavioral
      development].
AB  - The influence of daily all whiskers trimming from the 2nd or 9th to 20th
      postnatal day on maturation time of walking, rearing, grooming, manipulation
      activity and eye opening was studied in deprived rat pups and their sibs. In pups
      trimmed beginning from the day 2 and their sibs, eye opening occurs earlier.
      Also, grooming and rearing mature earlier, whereas manipulation activity forms
      later. The structure of correlations between maturation time of behavioral
      reactions and the day of eye opening changes. In pups trimmed beginning from the
      day 9, the majority of correlations disappears, dynamics of behavior development
      do not change. In their sib, maturation of manipulation activity is delayed, but
      changes in the structure of correlations are manifest less than in deprived pups.

PMID- 19591400
TI  - [Antigen stimulation modifies social behavior and chemosignals in male laboratory
      mice].
AB  - The injection of outbred ICR strain male mice with SRBC affected their dominance
      ability in pair-wise test. In pair-wise tests done without previous presentation
      of the smell of a contestant, the SRBC-treated males submitted to control males.
      This effect occurred within 3 days after the injection. However, on the third day
      after treatment, under conditions of getting pre-test olfactory information about
      a contestant, the dominance of SRBC treated-males over the control animals was
      observed. Perception of the contestant smell is known to lead to emotional
      reaction and could be accompanied by an increase in energy metabolism. This
      increase was significant in both the control submissive and SRBC-treated dominate
      males. Thus, the modification of mice smell perception due to antigen injection
      can affect the pair-wise competition.

PMID- 19591402
TI  - [Influence of terahertz (submillimeter) laser radiation on neurons in vitro].
AB  - The development of new sources of coherent non-ionizing radiation in terahertz
      wave range put forward the basic problems of revealing the mechanism of its
      action on biological objects, especially, on the nervous system. At this point it
      is necessary to reveal the radiation effects on complex molecular systems such as
      nerve cells. It was the main objective of this study. In the previous study we
      were the first to demonstrate highly specific effects of some examined
      wavelengths on the structural-functional properties of the nerve cells. The
      radiation of a free-electron laser produced damage to neuron morphology dependent
      on the power and wavelength. Transparent blank protrusions of the membrane,
      disorders of the growth of processes, and fall of the membrane potential were
      observed. The model developed and the data obtained approach the understanding of
      the molecular mechanisms of the effect of the waves under study on cells. These
      waves can be probably used as a tool for further investigation of functioning of
      neurons and neural system and correction of some pathology.

PMID- 19591401
TI  - [Reversible and irreversible stages of amnesia development after disruption of
      associative memory reactivation in snail].
AB  - We found previously that the inhibition of NMDA glutamate receptors during food
      aversion conditioning reactivation initiated disruption of long-term memory. In
      this work the dynamics of amnesia development was investigated. MK-801 (NMDA
      receptor antagonist) was injected into snail body cavity 24 hours after food
      aversion conditioning and conditioned food was presented (reminding
      procedure).Testing on the first and third days after the MK-801
      injection/reminding procedure revealed a gradual decrease in the number of
      conditioned food aversions. Repeated the-same-food aversion conditioning
      recovered the initial memory in these periods of time. The number of food
      aversions was minimal 10 days after the MK-810 injection/reminding. Repeated food
      aversion conditioning was ineffective and did not result in the formation of food
      aversion conditioning at that time. So we were the first who found that the long
      term memory reactivation disruption induced two stages of amnesia development.
      The first stage of amnesia development (up to 10 days) is reversible: the
      recovery of the long-term memory is possible after repeated the-same-food
      aversion conditioning. The second stage of amnesia development is irreversible:
      the recovery of the long-term memory is disrupted (revealed by the repeated the
      same-food aversion conditioning). The findings may be of value for understanding
      the mechanisms of acute amnesia after some neurological diseases or injuries.

PMID- 19591403
TI  - [Experimental model of anxiety-depression state in rats exposed to inhibitor of
      dipeptidyl peptidase IV methionyl-2(S)-cyano-pyrrolidine in early postnatal
      period].
AB  - The effects of irreversible synthetic inhibitor of dipeptidyl peptidase IV
      (DPPIV) methionyl-2(S)-cyano-pyrrolidine on behavior of adolescent and adult rats
      were studied. The inhibitor was administered in early postnatal period from day 5
      to day 19 (1 mg/kg, i.p.) in rat pups (males and females). In 1-2-month-old males
      treated with inhibitor of DPPIV, increased anxiety was revealed in the elevated
      plus maze and in the open field, 2- and 7-month-old males demonstrated the
      increased anxiety in a special battery of tests for evaluating anxiety-phobic
      states, whereas in female 1-3 months-old rats, the increased anxiety was observed
      in the elevated plus-maze. The depression-like behavior in the forced swimming
      test was revealed in 2-3 month-old males and in 2- and 7-month-old females.
      Adolescent and adult (1-2-month-old) rats of both genders and 7-month-old females
      demonstrated anhedonia in sucrose consumption/preference test. The findings prove
      the development of anxiety-depression-like state in rats postnatally exposed to
      inhibitor of DPPIV and suggest the DPPIV involvement in the development of
      anxiety and depression.

PMID- 19591404
TI  - [Estimation of the validity of variational characteristics of pre- and
      poststimulus EEG by the chi-square test].
AB  - Theoretical analysis of variational characteristics was performed and their
      practical validity was proved as applied to electroencephalogram. These
      characteristics are remarkable for both simplicity of computer calculation and
      the fact that they reflect the most essential features of an EEG curve with a
      highest possible compression.

PMID- 19591405
TI  - [Assessment for the image interpretation of 111In-ibritumomab tiuxetan in the
      phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or
      refractory indolent B-cell lymphoma].
AB  - Prior to the 90Y-ibritumomab tiuxetan (Y2B8) therapy, imaging is performed to
      verify the expected biodistribution of 111In-ibritumomab tiuxetan (In2B8). In
      order to determine the indication of radioimmunotherapy with Y2B8, the
      interpretation criteria for altered biodistribution of In2B8 was established. A
      phase II study of Y2B8 in patients with relapsed or refractory indolent B-cell
      lymphoma was performed in nine institutions in Japan. After the completion of the
      rituximab infusion at 250 mg/m2, 130 MBq of In2B8 was administered intravenously
      over 10 minutes. Gamma-camera imaging was performed at 2-24 hrs, 48-72 hrs, and
      90-144 hrs. Images were interpreted by two investigators including a nuclear
      physician at the individual institution according to the protocol defined
      criteria to determine the indication of the radioimmunotherapy. Forty-seven cases
      were enrolled in the study, and 45 cases underwent In2B8 scintigraphy. After the
      completion of the study, central assessment of the scintigram was performed by
      three nuclear physicians according to both the criteria of the phase II study and
      the latest version of the package insert of Zevalin in the United States of
      America. Two cases were judged as altered biodistribution based on both criteria.
      They demonstrated diffusely increased bone marrow uptake. The protocol defined
      criteria revealed additional two cases with altered biodistribution. They showed
      increased splenic uptake with facilitated blood clearance without increase in the
      bone marrow uptake. They received Y2B8 and no increment in the adverse event was
      noted as compared with cases with expected biodistribution. Then this type of
      biodistribution was not considered altered biodistribution. Increased focal bone
      marrow uptake was noted in other two cases. They were also considered within the
      limit of expected biodistribution. The present study recommends the following
      criteria for altered biodistribution of In2B8. 1) Diffusely increased bone marrow
      uptake simulating the super scan on bone scintigraphy, 2) Prominent uptake in all
      of the liver, spleen, and bone marrow, 3) Uptake in the lung, kidney, and
      intestine without lymphoma higher than the liver.

PMID- 19591406
TI  - [Chronological change in the national health insurance reimbursement based on the
      DPC package payment system regarding 131I internal therapy].
AB  - The national health reimbursement in 131I internal therapy for thyroid cancer and
      Graves' disease has increased by introducing the DPC package payment system. The
      thyroid cancer administration fee for shield room should be increased because of
      the strict regulation for 131I internal therapy, expensive equipments,
      confinement of radiopharmaceutical supply, and low efficiency in admission to
      shield rooms. In addition, the Graves' disease administration fee for shield room
      should be introduced since the inpatients undergo the same administration and
      care as the thyroid cancer inpatients.

PMID- 19591407
TI  - [Business administration of PET facilities: a cost analysis of three facilities
      utilizing delivery FDG].
AB  - BACKGROUND: PET (positron emission tomography) has been proved to be a powerful
      imaging tool in clinical oncology. The number of PET facilities in Japan has
      remarkably increased over the last decade. Furthermore, the approval of delivery
      FDG in 2005 resulted in a tremendous expansion of the PET institutions without a
      cyclotron facility. The aim of this study was to conduct a cost analysis of PET
      institutions that utilized delivery FDG. METHODS: Three PET facilities using
      delivery FDG were investigated about the costs for PET service. Fixed costs
      included depreciation costs for construction and medical equipments such as
      positron camera. Variable costs consisted of costs for medical materials
      including delivery FDG. The break-even point was analyzed in each of three
      institutions. RESULTS: In the three hospitals (A, B and C), the annual number of
      PET scan was 1,591, 1,637 and 914, while cost per scan was accounted as yen
      110,262, yen 111,091, and yen 134,192, respectively. The break-even point was
      calculated to be 2,583, 2,679 and 2,081, respectively. CONCLUSIONS: PET
      facilities utilizing delivery FDG seemed to have difficulty in business
      administration. Such a situation suggests the possibility that the current supply
      of PET facilities might exceed actual demand for the service. The efficiency of
      resource allocation should be taken into consideration in the future health
      service researches on PET.

PMID- 19591408
TI  - [Usefulness of FDG-PET for the diagnosis of copper deficiency at an early stage:
      a case report].
AB  - For the patients under long-term tube feeding, copper deficiency is known to be a
      cause of neutropenia and/or anemia. It is recognized as reversible
      myelodysplasia, since the condition improves by giving a copper supplementation.
      Myelodysplasia caused by copper deficiency is difficult to be diagnosed because
      it is not so common, and often it takes a long time to reach correct diagnosis.
      We reported usefulness of FDG-PET for the diagnosis of myelodysplasia caused by
      copper deficiency in early stage. The case was 46 y.o. male patient in vegetative
      state for 2 years after traumatic brain injury. Laboratory examination revealed
      slight leukopenia. PET/CT demonstrated high and diffuse FDG accumulation mainly
      in the vertebral bone marrow. Based on the lower levels of serum copper and
      ceruloprasmin, the patient was diagnosed as copper deficiency. After treatment of
      copper supplementation, FDG accumulation of the bone marrow disappeared, and the
      serum copper level has normalized. From the FDG-PET findings, even in the early
      stage of copper deficiency, high glucose metabolism of bone marrow was shown.

PMID- 19591409
TI  - Chrysler retirees lose dental benefits; here's what to do.

PMID- 19591411
TI  - Changes in our professional image.

PMID- 19591412
TI  - Michigan business tax deduction for dental materials and supplies.

PMID- 19591413
TI  - I overpaid my assistant and want my money back.

PMID- 19591410
TI  - Disagrees with editor's comments. Re: Access to care, part III: the dangers of
      free care.

PMID- 19591414
TI  - Advertising orthodontic treatment by a general practitioner.

PMID- 19591415
TI  - Your credit score is your best asset.

PMID- 19591416
TI  - Every CDT code is not a 'benefit'.

PMID- 19591417
TI  - What you need to know about the new amalgam separator requirements: part one.

PMID- 19591419
TI  - Global gathering of nurses seeks solutions to their shared concerns.

PMID- 19591420
TI  - All our yesterdays.
AB  - The Retired Nurses National Home in Bournemouth has been offering care and
      support since 1937 Its residents enjoy a range of activities, share career
      experiences and keep in touch with the profession as it is today.

PMID- 19591421
TI  - Any time, any place.
AB  - An RCN and Open University merger has greatly improved access to education for
      nurses in the UK and around the world.

PMID- 19591418
TI  - What you should know about mandatory continuing education.

PMID- 19591422
TI  - Cautionary tales for thrill seekers.
AB  - Animal to human transmission of disease is not new but foreign travel and the
      keeping of imported pets has focused attention on an intriguing pattern of
      emerging cases.

PMID- 19591423
TI  - Food for thought.
AB  - Healthy eating habits established in childhood can persist throughout adult life.
      But many toddlers are fed a diet of takeaways and ready meals.

PMID- 19591424
TI  - In the autumn of '69.

PMID- 19591425
TI  - Guidance on maintaining personal hygiene in nail care.
AB  - Nail care is important in the maintenance of personal hygiene and is an essential
      aspect of patient care. Confusion about who should perform nail care for patients
      has resulted in poor practice and cycles of non-activity. This article provides
      guidance for nurses on performing routine nail care.

PMID- 19591426
TI  - The role of dining companions in supporting nursing care.
AB  - Malnutrition in hospitals is an ongoing international issue. Research indicates
      that there are many barriers to nutritional care, including lack of nursing time,
      knowledge and understanding. The Chelsea and Westminster Hospital NHS Foundation
      Trust runs an annual audit on standards of nutritional screening and subsequent
      care. To fulfil the organisation's objective of focusing on patient safety and
      quality of care, the hospital has developed a multidisciplinary approach to
      malnutrition that includes using volunteers as dining companions.

PMID- 19591428
TI  - Stab wounds.

PMID- 19591427
TI  - Obesity risk: importance of the waist-to-height ratio.
AB  - This article reviews the benefits and limitations of some of the different
      anthropometric measures to assess the health risks of obesity. Those covered are
      the body mass index, the waist-to-hip ratio, waist circumference and the waist-to
      height ratio. The latter has the potential to be globally applicable to different
      ethnic populations and to children and adults. The suggested boundary values of
      0.5 and 0.6 are used in a shape chart and shape calculator, described here, to
      indicate different levels of health risk in adults and children. A simple message
      from this work is 'keep your waist circumference to less than half your height'.

PMID- 19591429
TI  - Record of achievement.

PMID- 19591430
TI  - Extra training brings added value.

PMID- 19591431
TI  - The art of persuasion.

PMID- 19591433
TI  - Improved measurement of ozone and carbonyls using a dual-bed sampling cartridge
      containing trans-1,2-bis(2-pyridyl)ethylene and 2,4-dinitrophenylhydrazine
      impregnated silica.
AB  - We have previously developed a new method using trans-1,2-bis-(4-pyridyl)ethylene
      (4-BPE) and 2,4-dinitrophenylhydrazine (DNPH) for the simultaneous determination
      of ozone and carbonyls in air using a two-bed cartridge system. In this method, 4
      BPE was used to capture ozone. However, the method suffered from long reaction
      times in the eluate, low solubility of the DNPH derivative, and a strong
      dependence on atmospheric moisture. These problems could be overcome by using
      trans-1,2-bis-(2-pyridyl)ethylene (2-BPE) in place of 4-BPE. The efficiency of
      the reaction of ozone with 2-BPE to form pyridine-2-aldehyde (2PA) is higher than
      the corresponding reaction with 4-BPE. Under the optimized elution conditions,
      the reaction times of 2PA and 4PA with DNPH are within 15 and 120 min,
      respectively. In the elution from the sampling cartridge, 2PA formed from 2-BPE
      and ozone is easier to dissolve in the elution solvent. A stronger influence of
      humidity was observed in ozone recovery by the 4-BPE/DNPH method. 2-BPE exhibits
      a maximum reaction efficiency of 84% at 32% relative humidity (RH), while 4-BPE
      attains a maximum reaction efficiency of 82% at 49% RH. Humidity has much less
      influence on the reaction of 2-BPE with ozone. Above 18% RH, the reaction
      efficiency of 2-BPE with ozone is in the range 80-84%. Thus, 2-BPE is the more
      useful reagent for ozone analysis. The concentrations of ozone and carbonyls by
      the improved 2-BPE/DNPH method corresponded with the mean value by an ozone auto
      analyzer in an air monitoring station and a DNPH cartridge coupled with a KI
      ozone scrubbing cartridge.

PMID- 19591432
TI  - Compositional analysis of heparin/heparan sulfate interacting with fibroblast
      growth factor.fibroblast growth factor receptor complexes.
AB  - Heparan sulfate (HS) proteoglycans (PGs) interact with a number of extracellular
      signaling proteins, thereby playing an essential role in the regulation of many
      physiological processes. One major function of HS is to interact with fibroblast
      growth factors (FGFs) and their receptors (FGFRs) and form FGF.HS.FGFR signaling
      complexes. Past studies primarily examined the selectivity of HS for FGF or FGFR.
      In this report, we used a new strategy to study the structural specificity of HS
      binding to 10 different FGF.FGFR complexes. Oligosaccharide libraries prepared
      from heparin, 6-desulfated heparin, and HS were used for the interaction studies
      by solution competition surface plasmon resonance (SPR) and filter trapping
      assays. Specific oligosaccharides binding to FGF.FGFR complexes were subjected to
      polyacrylamide gel electrophoresis (PAGE) analysis and disaccharide compositional
      analysis using liquid chromatography and mass spectrometry. The competition SPR
      studies using sized oligosaccharide mixtures showed that binding of each of the
      tested FGFs or FGF.FGFR complexes to heparin immobilized to an SPR chip was size
      dependent. The 6-desulfated heparin oligosaccharides exhibited a reduced level of
      inhibition of FGF and FGF.FGFR complex binding to heparin in the competition
      experiments. Heparin and the 6-desulfated heparin exhibited higher levels of
      inhibition of the FGF.FGFR complex binding to heparin than of FGF binding to
      heparin. In the filter trapping experiments, PAGE analysis showed different
      affinities between the FGF.FGFR complexes and oligosaccharides. Disaccharide
      analysis showed that HS disaccharides with a degree of polymerization of 10
      (dp10) had high binding selectivity, while dp10 heparin and dp10 6-desulfated
      heparin showed reduced or no selectivity for the different FGF.FGFR complexes
      tested.

PMID- 19591435
TI  - Mechanistic study of LiNH(2)BH(3) formation from (LiH)(4) + NH(3)BH(3) and
      subsequent dehydrogenation.
AB  - The formation of LiNH(2)BH(3) from (LiH)(4) and NH(3)BH(3) and the subsequent
      dehydrogenation have been studied computationally at the CCSD(T)/6
      311++G(3d,2p)//MP2/6-311++G(2d,p) level. A cubic unit of (LiH)(4) is predicted to
      react readily with NH(3)BH(3) to form LiNH(2)BH(3) plus H(2). The (LiH)(4)
      tetramer enables dehydrogenation through the exchange of a hydride vertex of
      (LiH)(4) and NH(2)BH(3)(-) where NH(2)BH(3)(-) is formed when the hydride vertex
      of (LiH)(4) abstracts a proton from NH(3). The free energy of activation for loss
      of H(2) is reduced from 37.2 kcal/mol in NH(3)BH(3) to 11.0 kcal/mol in (LiH)(4)
      + NH(3)BH(3). Further, H(2) elimination from the (LiNH(2)BH(3))(2) dimer is
      predicted to be much easier than from the monomer which may suggest a cooperative
      H(2)-loss mechanism is possible in solid LiNH(2)BH(3). While two molecules of
      H(2) can be lost reversibly from (LiNH(2)BH(3))(2), loss of further H(2)
      molecules is more difficult but could occur if the lattice energy stabilization
      accompanying H(2) loss is sufficiently large.

PMID- 19591436
TI  - Biomimetically triggered inorganic crystal transformation by biomolecules: a new
      understanding of biomineralization.
AB  - Phase transformation is an important strategy in biomineralization. However, the
      role of biomolecules in the mineral transition is poorly understood despite the
      fact that the biomineralization society greatly highlights the organic controls
      in the formation of the inorganic phase. Here, we report an induced biomimetic
      phase transformation from brushite (a widely used calcium phosphate precursor in
      biological cement) to hydroxyapatite (main inorganic composition of skeletal
      mineral) by citrate (a rich organic component in bone tissue). The transformation
      in the absence of the organic additive cannot be spontaneously initiated in an
      aqueous solution with a pH of 8.45 (no phase transition is detected in 4 days),
      which is explained by a high interfacial energy barrier between brushite-solution
      and hydroxyapatite-solution interfaces. Citrate can oppositely regulate these two
      interfaces, which decreases and increases the stabilities of brushite and
      hydroxyapatite surfaces in the solution, respectively. Thus, the interfacial
      energy barrier can be greatly reduced in the presence of citrate and the reaction
      is triggered; e.g., at 1 mM citrate, the total transformation from brushite to
      hydroxyapatite can be completed within 3 days. The relationship between the
      transition kinetics and citrate concentration is also studied. The work reveals
      how the organic components direct solid-solid phase transformation, which can be
      understood by an energetic control of the interfacial barrier. It is emphasized
      that the terms of interfacial energy must be taken into account in the studies of
      phase transformation. We suggest that this biomimetic approach may provide an in
      depth understanding of biomineralization.

PMID- 19591437
TI  - Evidence for trisulfide bonds in a recombinant variant of a human IgG2 monoclonal
      antibody.
AB  - The hinge region of human IgG2 contains four cysteine residues involved in
      disulfide linkages between the heavy chains, as well as the heavy and light
      chains. These linkages provide the fundamental framework of three distinct IgG2
      disulfide isoforms recently described. Here, we detail another, disulfide-related
      post-translational modification in a recombinant variant of human IgG2.
      Heterogeneity associated with this antibody was separated into several fractions
      by anion-exchange chromatography (AEX), which is an important initial step that
      highlights the resolving power of surface charge-based HPLC techniques. Mass
      spectrometry of the intact antibody revealed weakly resolved discrete covalent
      additions of 25-35 Da in one of the two main AEX fractions. Digestion by
      endoproteinase Lys-C performed under nonreducing conditions, as well as tandem MS
      experiments, narrowed the modification to the peptide-containing disulfide
      bridged hinge structure. High mass resolution and accuracy measurements of the
      peptide strongly suggested an addition of one or two S atoms. The modification
      could be eliminated by a mild reducing treatment of the intact antibody. Overall,
      these findings are consistent with the replacement of up to two disulfide bridges
      (S-S) with a like number of trisulfides (S-S-S) in the antibody hinge. The
      trisulfide modification is rather uncommon for proteins and its possible origins
      in the IgG2 variant are discussed.

PMID- 19591434
TI  - Biophysical investigation of GpIbalpha binding to thrombin anion binding exosite
      II.
AB  - Substrates and cofactors of the serine protease thrombin (IIa) employ two anion
      binding exosites (ABE-I and -II) to aid in binding. On the surface of platelets
      resides the GpIbalpha/beta-GpIX-GpV membrane-bound receptor complex. IIa's ABE-II
      is proposed to interact with an anionic portion of GpIbalpha which enhances IIa
      cleavage of PAR-1 and subsequent activation of platelets. In this work, one
      dimensional (1D) and two-dimensional (2D) NMR, analytical ultracentrifugation
      (AUC), and hydrogen-deuterium exchange (HDX) coupled with MALDI-TOF MS were
      performed to further characterize the features of binding to IIa's ABEs. The
      described work builds upon investigations performed in a prior study with
      fibrin(ogen)'s gamma' peptide and IIa [Sabo, T. M., Farrell, D. H., and Maurer,
      M. C. (2006) Biochemistry 45, 7434-7445]. 1D line broadening NMR (1H and 31P) and
      2D trNOESY NMR studies indicate that GpIbalpha residues D274-E285 interact
      extensively with the IIa surface in an extended conformation. AUC demonstrates
      that both GpIbalpha (269-286) and gamma' (410-427) peptides interact with IIa
      with a 1:1 stoichiometry. When the HDX results are compared to those for the ABE
      I targeting peptide hirudin (54-65), the data imply that GpIbalpha (269-286),
      GpIbalpha (1-290), and gamma' (410-427) are indeed directed to ABE-II. The ABE-II
      binding fragments reduce HDX for sites distant from the interface, suggesting
      long-range conformational effects. These studies illustrate that GpIbalpha and
      gamma' target ABE-II with similar consequences on IIa dynamics, albeit with
      differing structural features.

PMID- 19591438
TI  - Insight into ramsdellite LI(2)Ti(3)O(7) and its proton-exchange derivative.
AB  - Despite being proven to be a good lithium-ion conductor 30 years ago, the crystal
      structure of the ramsdellite-like Li(2)Ti(3)O(7) has remained uncertain, with two
      potential models for locating the lithium ions in the structure. Although the
      model presently accepted states that both lithium and titanium occupy the
      octahedral sites in the framework, evidence against this model are provided by
      (6)Li and (7)Li MAS NMR spectroscopy. Thus, about 14% of these octahedral
      positions are empty since no lithium in octahedral coordination is present in the
      material. When Li(2)Ti(3)O(7)-ramsdellite is treated with nitric acid a complete
      exchange of lithium by protons is produced to yield H(2)Ti(3)O(7). The crystal
      structure of this proton-exchanged ramsdellite has been re-examined combining X
      ray diffraction (XRD), neutron powder diffraction (NPD), and spectroscopic ((1)H
      and (7)Li MAS NMR) techniques. Two kinds of protons are present in this material
      with different acidity because of the local environments of oxygen atoms to which
      protons are bonded, namely, low acidic protons strongly bonded to highly charged
      oxygen atoms (coordinated to two Ti(4+) and a vacancy); and protons linked to low
      charged oxygen atoms (bonded to three Ti(4+) ions) which will display a more
      acidic behavior. H(2)Ti(3)O(7) absorbs water; proton mobility is enhanced by the
      presence of absorbed water, giving rise to a large improvement of its electrical
      conductivity in wet atmospheres. Thus, it seems that water molecules enter the
      tunnels in the structure providing a vehicle mechanism for proton diffusion.

PMID- 19591439
TI  - Surfactant-assisted hydrothermal synthesis of Eu(3+)-doped white light hydroxyl
      sodium yttrium tungstate microspheres and their conversion to NaY(WO(4))(2).
AB  - In this work, large-scale three-dimensional "flake-ball" microarchitectures of
      Eu(3+) doped white light hydroxyl sodium yttrium tungstate were prepared by the
      well-known hydrothermal approach at 180 degrees C for 48 h in the presence of
      triblock-copolymer poly(ethylene glycol)-block-poly(propylene glycol)-block
      poly(ethylene glycol) (P123). NaY(WO(4))(2):Eu(3+) phosphor was formed by
      annealing the hydrothermal product at approximately 630 degrees C for 2 h. A time
      dependent microstructure evolution study was performed under hydrothermal
      reaction. The evolution process is the self-assembly process of P123, and the
      effects of other reaction parameters, such as influence of the concentration of
      P123 on morphology, and the influence of temperature on PL. The mechanism by
      which the "flake-ball" particles are formed is discussed in detail. The PL
      spectra of Eu(3+)-doped hydroxyl sodium yttrium tungstate phosphor contain two
      parts: the broad blue-green band and the (5)D(0)-->(7)F(J) (J = 1, and 2)
      characteristic transition of Eu(3+). This approach provides a facile route for
      the production of high-quality hydroxyl sodium yttrium tungstate microstructures
      with an interesting optical property.

PMID- 19591440
TI  - Structural, luminescent, and magnetic properties of three novel three-dimensional
      metal-organic frameworks based on hexadentate N,N'-bis(4-picolinoyl)hydrazine.
AB  - Three novel microporous three-dimensional (3-D) metal-organic framework materials
      [ML](n) [M = Ni, Co, Cd; L = N,N'-bis(4-picolinoyl)hydrazine] were obtained from
      hydrothermal reactions. The organic ligand L was formed through the in situ ring
      opening hydrolysis reaction of 2,5-bis(4-pyridyl)-1,3,4-oxadiazole with the
      assistance of metal ions. Single-crystal X-ray diffraction studies reveal that
      complexes 1-3 adopt 6-connected 3-D networks of distorted alpha-Po topology,
      which are built from non-interpenetrated (4,4) grids cross-linked by zigzag
      chains. These isomorphic complexes are all of high thermal stability, but some
      other physical properties are quite different because of their different metal
      centers. Antiferromagnetic exchange was observed between Ni(II) centers of
      complex 1, while ferromagnetic for Co(II) centers of complex 2. Complex 3
      exhibits strong fluorescence emission.

PMID- 19591441
TI  - Injection, transport, absorption and phosphorescence properties of a series of
      blue-emitting Ir(III) emitters in OLEDs: a DFT and time-dependent DFT study.
AB  - Quantum-chemistry methods were explored to investigate the electronic structures,
      injection and transport properties, absorption and phosphorescence mechanism of a
      series of blue-emitting Ir(III) complexes {[(F(2)-ppy)(2)Ir(pta -X/pyN4)], where
      F(2)-ppy = (2,4-difluoro)phenylpyridine; pta = pyridine-1,2,4-triazole; X =
      phenyl(1); p-tolyl (2); 2,6-difluororophenyl (3); -CF(3) (4), and pyN4 = pyridine
      1,2,4-tetrazolate (5)}, which are used as emitters in organic light-emitting
      diodes (OLEDs). The mobility of hole and electron were studied computationally
      based on the Marcus theory. Calculations of Ionization potentials (IPs) and
      electron affinities (EAs) were used to evaluate the injection abilities of holes
      and electrons into these complexes. The reasons for the lower EL efficiency and
      phosphorescence quantum yields in 3-5 than in 1and 2 have been investigated.
      These new structure-property relationships can guide an improved design and
      optimization of OLED devices based on blue-emitting phosphorescent Ir(III)
      complexes.

PMID- 19591442
TI  - Solvolytic reactivity of heptafluorobutyrates and trifluoroacetates.
AB  - A series of X,Y-substituted benzhydryl heptafluorobutyrates (1-6-HFB) and
      trifluoroacetates (1-6-TFA) were subjected to solvolysis in various
      methanol/water, ethanol/water, and acetone/water mixtures at 25 degrees C. The
      LFER equation log k = s(f)(E(f) + N(f)) was used to derive the nucleofuge
      specific parameters (N(f) and s(f)) for S(N)1-type reaction. In comparison with
      TFA, the HFB leaving group is a better nucleofuge for less than 0.5 unit of N(f).
      X,Y-Substituted benzhydryl trifluoroacetates solvolyze by way of S(N)1 reactions
      unless electron-withdrawing groups are attached to aromatic rings. In such cases
      the substrates solvolyze faster than predicted for the S(N)1 route because of the
      change in mechanism. X,Y-Substituted benzhydryl heptafluorobutyrates examined
      here (E(f) > or = -7.7) solvolyze according to the S(N)1 pathway. The almost
      parallel log k vs. E(f) lines in various solvents for HFBs and TFAs, and the
      corresponding slope parameters (s(f) are in the range of 0.91 and 0.83), indicate
      early TS with moderately advanced charge separation. NBO charges of HFB and TFA
      anions and the affinities obtained, all calculated at the PCM-B3LYP/6
      311+G(2d,p)//PCM-B3LYP/6-311+G(2d,p) level, revealed that the HFB anion slightly
      better delocalizes the developing negative charge than TFA, and that the affinity
      of the benzhydrylium ion is slightly larger toward TFA than toward the HFB anion,
      which is in accordance with the greater solvolytic reactivity of HFB.

PMID- 19591443
TI  - Synthesis of all possible isomers corresponding to the proposed structure of
      montanacin E, and their antitumor activity.
AB  - Total synthesis of 4 and its three diastereomers is described. The key steps
      involve stereoselective formation of the tetrahydrofuran ring by a cascade
      cyclization of hydroxy tosylate 7 and an intermolecular cross metathesis between
      a tetrahydrofuran 5 and a gamma-lactone 6. Spectroscopic data of 4 and
      biosynthetic hypothesis strongly suggest it to be montanacin E. Inhibitory
      activities of 4 and its isomers against six human solid tumor cell lines were
      also evaluated.

PMID- 19591444
TI  - Binding entropy and its application to solids.
AB  - The concept of binding entropy is introduced and information theoretical approach
      is combined with orbital-free density functional theory. It is shown that binding
      entropy expresses the deviation of the molecular electron density from the
      promolecular density and the deviation of the molecular kinetic energy density
      from the promolecular kinetic energy density. The change of the kinetic energy
      density during the chemical bond formation explicitly appears in the binding
      entropy expression. The binding entropy and binding entropy density are analyzed
      using experimental electron density for solid germanium, gallium arsenide and
      dinitrogen tetroxide. It is demonstrated that the binding entropy joined with
      deformation electron density and "deformation" kinetic energy density, carries
      information about both the bonding and binding details and provides a deeper
      insight into the nature of chemical bond. Atomic and global binding entropies
      also appeared to be useful descriptors giving a compact description of chemical
      binding.

PMID- 19591445
TI  - Principal role of the stepwise aggregation mechanism in ionic surfactant
      solutions near the critical micelle concentration. Molecular dynamics study.
AB  - The validity of the assumption on the predominant contribution of the stepwise
      processes to the ionic micelle formation/destruction in the vicinity of critical
      micelle concentration was investigated by molecular dynamics simulation. A coarse
      grained model was used to describe the surfactant/water mixture. The cluster size
      distribution was estimated directly from molecular dynamics simulations or
      obtained from a reduced set of kinetic equations. The good agreement between two
      approaches shows that the neglect of the terms responsible for cluster
      fusion/fission is fully justified and that such processes are less important than
      stepwise aggregation.

PMID- 19591446
TI  - Mechanical interferometry of nanoscale motion and local mechanical properties of
      living zebrafish embryos.
AB  - We present an interferometric imaging technique that permits local measurement of
      mechanical properties and nanomechanical motion in small living animals.
      Measurements of nanomechanical properties and spatially resolved pulsations of
      <60 nm were recorded for the developing eye of a living zebrafish (Danio rerio)
      embryo, an important model organism. We also used magnetic microreflectors to
      conduct contact nanomechanical indentation measurements of the stiffness of the
      embryonic eye.

PMID- 19591448
TI  - Determining elemental composition using prompt gamma activation analysis.
AB  - Prompt gamma-ray spectra sometimes contain hundreds of characteristic peaks, and
      the masses of the sample components can be determined from dozens of gamma-ray
      peak areas, some of which are affected by spectral interferences. Reliable
      qualitative and quantitative analyses can only be performed by using a precisely
      calibrated detector system, an accurate spectroscopic data library, high-quality
      spectroscopy software, and a sophisticated method to convert raw data into
      chemical composition. This article describes the steps of the chemical analysis
      with prompt gamma activation analysis (PGAA). A complete data reduction method
      has been constructed that handles the large number of spectral peaks using
      statistical procedures, identifies the chemical components based on statistical
      criteria, and determines the sample composition with a least-squares fit of the
      masses calculated from the individual peaks. The calculation of the uncertainties
      as well as the detection and analytical limits are discussed in detail. The
      validation of the method is also presented. The method can also be used in the
      evaluation of the results of other spectroscopic techniques.

PMID- 19591447
TI  - Multiparameter structural optimization of single-walled carbon nanotube
      composites: toward record strength, stiffness, and toughness.
AB  - Efficient coupling of mechanical properties of SWNTs with the matrix leading to
      the transfer of unique mechanical properties of SWNTs to the macroscopic
      composites is a tremendous challenge of today's materials science. The typical
      mechanical properties of known SWNT composites, such as strength, stiffness, and
      toughness, are assessed in an introductory survey where we focused on concrete
      numerical parameters characterizing mechanical properties. Obtaining ideal stress
      transfer will require fine optimization of nanotube-polymer interface. SWNT
      nanocomposites were made here by layer-by-layer (LBL) assembly with poly(vinyl
      alcohol) (PVA), and the first example of optimization in respect to key
      parameters determining the connectivity at the graphene-polymer interface,
      namely, degree of SWNT oxidation and cross-linking chemistry, was demonstrated.
      The resulting SWNT-PVA composites demonstrated tensile strength (sigma(ult)) =
      504.5 +/- 67.3 MPa, stiffness (E) = 15.6 +/- 3.8 GPa, and toughness (K) = 121.2
      +/- 19.2 J/g with maximum values recorded at sigma(ult) = 600.1 MPa, E = 20.6
      GPa, and K = 152.1 J/g. This represents the strongest and stiffest nonfibrous
      SWNT composites made to date outperforming other bulk composites by 2-10 times.
      Its high performance is attributed to both high nanotube content and efficient
      stress transfer. The resulting LBL composite is also one of the toughest in this
      category of materials and exceeding the toughness of Kevlar by 3-fold. Our
      observation suggests that the strengthening and toughening mechanism originates
      from the synergistic combination of high degree of SWNT exfoliation, efficient
      SWNT-PVA binding, crack surface roughening, and fairly efficient distribution of
      local stress over the SWNT network. The need for a multiscale approach in
      designing SWNT composites is advocated.

PMID- 19591449
TI  - Acoustic differential extraction for forensic analysis of sexual assault
      evidence.
AB  - Forensic DNA analysis of samples obtained from sexual assault evidence relies on
      separation of male and female components of the recovered genetic material. The
      conventional separation method used by crime laboratories, differential
      extraction (DE), is one of the most time-consuming sample preparation steps,
      requires extensive sample handling, is difficult to automate, and often results
      in inefficient separation of female DNA from the male sample components. To
      circumvent conventional DE, acoustic differential extraction (ADE) analysis was
      developed on a microfluidic device. The ADE method relies on acoustic trapping of
      sperm cells in the presence of epithelial cell lysate (which is unretained), and
      laminar flow valving to direct the male and female fractions to separate outlets.
      Following the separation of sperm from epithelial cell lysate, DNA extraction,
      quantitation, amplification, and separation were performed using conventional
      laboratory methods. The results show that highly purified male and female
      fractions can be obtained with the ADE microdevice from mock sexual assault
      samples in 14 min. ADE analysis provides the potential to significantly alter the
      means by which sexual assault evidence is processed in crime laboratories.

PMID- 19591451
TI  - Antimalarial activity of azafluorenone alkaloids from the Australian tree
      Mitrephora diversifolia.
AB  - Mass-directed isolation of the CH2Cl2/MeOH extract from the roots of the
      Australian tree Mitrephora diversifolia resulted in the purification of the new
      azafluorenone alkaloid 5,8-dihydroxy-6-methoxyonychine (1) together with the
      known natural product 5-hydroxy-6-methoxyonychine (2). The structures of 1 and 2
      were determined by extensive 1D and 2D NMR and MS data analyses. Both compounds
      were isolated during a drug discovery program aimed at the identification of new
      antimalarial leads from a prefractionated natural product library. When tested
      against two different strains of the parasite Plasmodium falciparum (3D7 and
      Dd2), 2 displayed IC(50) values of 9.9 and 11.4 microM, respectively, while 1
      showed minimal activity.

PMID- 19591452
TI  - Near-field optical study of protein transport kinetics at a single nuclear pore.
AB  - The kinetics of proteins passing through individual nuclear pore complexes (NPCs)
      of the nuclear envelope (NE) was studied using near-field scanning optical
      microscopy (NSOM) in combination with fluorescence correlation spectroscopy
      (FCS). The NSOM probe was placed over a single pore in an unsupported native NE
      to observe fluorescence-labeled NTF2 moving in the transport channel. A
      correlation analysis of the arising fluorescence fluctuations enabled us to
      characterize the translocation as driven by Brownian motion and to determine the
      related kinetic constants. Though trapped in the pore, NTF2 turned out to be
      highly mobile within a large axial extension. Our findings support the idea that
      molecules in transit interact with NPC proteins containing phenylalanine-glycine
      repeat domains at the periphery of the channel. NSOM-FCS may help to understand
      the facilitated translocation in more detail and offers a new way to study single
      molecule mobility on a nanoscale.

PMID- 19591453
TI  - Secondary amine formation from reductive amination of carbonyl compounds promoted
      by Lewis acid using the InCl3/Et3SiH system.
AB  - A robust and reliable method has been developed for reductive amination of
      primary amines with various aldehydes and ketones using Zn(ClO(4))(2) x 6 H(2)O
      as a catalyst. [In-H] generated in situ via a combination of InCl(3) and Et(3)SiH
      is employed as an effective reducing system. A variety of secondary amines can be
      synthesized in a one-pot procedure in excellent yields.

PMID- 19591454
TI  - Thermal intramolecular [4 + 2] cycloadditions of allenamides: a stereoselective
      tandem propargyl amide isomerization-cycloaddition.
AB  - A stereoselective intramolecular normal demand [4 + 2] cycloaddition of
      allenamides under thermal conditions without metal assistance is described. This
      work led to the development of a stereoselective tandem propargyl amide
      isomerization-[4 + 2] cycloaddition sequence amenable for rapid assembly of
      complex nitrogen heterocycles.

PMID- 19591455
TI  - Multispectral thin film biosensing and quantitative imaging using 3D plasmonic
      crystals.
AB  - This work provides plasmonic crystal platforms for quantitative imaging mode
      biosensing and multispectral immunoassays, establishing and validating both the
      optical and equilibrium bases for their operation. We investigated the distance
      dependent refractive index sensitivity of full 3D plasmonic crystals to thin
      polymeric films formed using layer by layer (LbL) assembly of polyelectrolytes as
      a model system. LbL was also used to determine the preferred gold thickness and
      plasmonic crystal design rules (nanowell diameter and periodicity) for improved
      thin-film sensitivity, and full 3D finite-difference time-domain (FDTD)
      calculations were used to quantitatively model and confirm the experimentally
      observed thin film sensitivities. The integrated multispectral response of the
      crystals increases approximately linearly with film thickness for values <70 nm,
      which enables the use of molecular rulers with known thicknesses (such as self
      assembled monolayers of alkanethiols on gold) to calibrate these optics for
      quantitative detection and speciation of surface binding events in a multiplexed
      imaging format. The utility of these sensors and multispectral analysis for
      applications in quantitative biosensing was further demonstrated by measuring the
      equilibrium response curve of an antibody/antigen pair (rabbit antigoat IgG/goat
      IgG) at increasing antigen concentrations. Fitting the integrated response to a
      Langmuir isotherm yielded a calculated binding constant on the order of
      approximately 10(7) M(-1), which is in agreement with the affinity constants
      reported in the literature for anti-IgG/IgG binding pairs and provides intrinsic
      detection limits of approximately 400 pM for such unamplified assays.

PMID- 19591457
TI  - N-tosyl-L-phenylalanine chloromethyl ketone inhibits NF-kappaB activation by
      blocking specific cysteine residues of IkappaB kinase beta and p65/RelA.
AB  - N-Tosyl-L-phenylalanine chloromethyl ketone (TPCK), a serine/cysteine protease
      inhibitor, has been reported to inhibit expression of inflammatory mediators by
      blocking nuclear factor-kappaB (NF-kappaB) activation. We examined the effect of
      TPCK on the NF-kappaB activation pathway in HeLa cells by measuring the activity
      of IkappaB kinase (IKK) and p65/RelA-DNA binding. TPCK inhibited tumor necrosis
      factor-alpha-induced IKK activation and directly blocked IKK activity in vitro.
      TPCK-induced inhibition of NF-kappaB and IKK activation was abrogated by addition
      of the thiol-reducing agent dithiothreitol, suggesting that the effect of TPCK
      occurred through modification of a thiol group in IKK. Consistent with this, an
      IKKbeta mutant in which Cys-179 was substituted with alanine was not more
      susceptible to TPCK. Our result also showed that TPCK inhibits the DNA binding of
      transiently expressed p65/RelA in HeLa cells. Inhibition of p65/RelA-DNA binding
      was recovered in the presence of dithiothreitol, and substitution of Cys-38 with
      Ser in p65/RelA rendered the protein resistant to inhibition by TPCK. Mass
      spectrometry analysis of IKKbeta and p65/RelA isolated from cells treated with
      TPCK by UPLC-ESI-Q-TOF tandem MS revealed the labeling of Cys-179 of IKKbeta and
      Cys-38 of p65/RelA with a tosylphenylalanylmethyl group. These results suggest
      that TPCK inhibits NF-kappaB activation by directly modifying thiol groups on two
      different targets: Cys-179 of IKKbeta and Cys-38 of p65/RelA.

PMID- 19591458
TI  - Neutron diffraction study of the in situ oxidation of UO(2).
AB  - This paper discusses uranium oxide crystal structure modifications that are
      observed during the low-temperature oxidation which transforms UO(2) into
      U(3)O(8). The symmetries and the structural parameters of UO(2), beta-U(4)O(9),
      beta-U(3)O(7), and U(3)O(8) were determined by refining neutron diffraction
      patterns on pure single-phase samples. Neutron diffraction patterns were also
      collected during the in situ oxidation of powder samples at 483 K. The lattice
      parameters and relative ratios of the four pure phases were measured during the
      progression of the isothermal oxidation. The transformation of UO(2) into
      U(3)O(8) involves a complex modification of the oxygen sublattice and the onset
      of complex superstructures for U(4)O(9) and U(3)O(7), associated with regular
      stacks of complex defects known as cuboctahedra, which consist of 13 oxygen
      atoms. The kinetics of the oxidation process are discussed on the basis of the
      results of the structural analysis.

PMID- 19591459
TI  - Side-on coordination of a P-P bond in heterobinuclear tetraphosphorus complexes
      with a [Si(mu,eta(2:2)-P(4))Ni] core and nickel(I) centers.
AB  - The synthesis and characterization of the first heterobinuclear tetraphosphorus
      complexes 3a and 3b with a [Si(mu,eta(2:2)-P(4))Ni] core are reported. The latter
      result from conversion of the silylene-activated P(4) ligand LSiP(4) (1; L =
      CH[(C horizontal lineCH(2))CMe][N(2,6-(i)Pr(2)C(6)H(3))](2)) with the beta
      diketiminatonickel(I) complexes [(L'Ni)(2).toluene] (L' = CH[CMeN(2,6
      iPr(2)C(6)H(3))](2)) and [(L''Ni)(2).toluene] (L'' = CH[CMeN(2,6
      Et(2)C(6)H(3))](2)), respectively. Unexpectedly, the complexes 3a and 3b feature
      a [Si(mu,eta(2:2)-P(4))Ni] core with nickel(I) centers as shown by X-ray
      diffraction analysis, electron paramagnetic resonance, and magnetic measurements.
      The latter prove that the products are paramagnetic both in the solid state and
      in solution because of the presence of tetrahedral nickel(I) sites.

PMID- 19591456
TI  - Magnetic nanoparticle drug carriers and their study by quadrupole magnetic field
      flow fractionation.
AB  - Magnetic nanoparticle drug carriers continue to attract considerable interest for
      drug targeting in the treatment of cancers and other pathological conditions. The
      efficient delivery of therapeutic levels of drug to a target site while limiting
      nonspecific, systemic toxicity requires optimization of the drug delivery
      materials, the applied magnetic field, and the treatment protocol. The history
      and current state of magnetic drug targeting is reviewed. While initial studies
      involved micrometer-sized and larger carriers, and work with these microcarriers
      continues, it is the sub-micrometer carriers or nanocarriers that are of
      increasing interest. An aspect of magnetic drug targeting using nanoparticle
      carriers that has not been considered is then addressed. This aspect involves the
      variation in the magnetic properties of the nanocarriers. Quadrupole magnetic
      field-flow fractionation (QMgFFF) is a relatively new technique for
      characterizing magnetic nanoparticles. It is unique in its capability of
      determining the distribution in magnetic properties of a nanoparticle sample in
      suspension. The development and current state of this technique is also reviewed.
      Magnetic nanoparticle drug carriers have been found by QMgFFF analysis to be
      highly polydisperse in their magnetic properties, and the strength of response of
      the particles to magnetic field gradients is predicted to vary by orders of
      magnitude. It is expected that the least magnetic fraction of a formulation will
      contribute the most to systemic toxicity, and the depletion of this fraction will
      result in a more effective drug carrying material. A material that has a reduced
      systemic toxicity will allow higher doses of cytotoxic drugs to be delivered to
      the tumor with reduced side effects. Preliminary experiments involving a novel
      method of refining a magnetic nanoparticle drug carrier to achieve this result
      are described. QMgFFF is used to characterize the refined and unrefined material.

PMID- 19591460
TI  - Design and synthesis of coumarin-based Zn(2+) probes for ratiometric fluorescence
      imaging.
AB  - The physiological roles of free Zn(2+) have attracted great attention. To clarify
      those roles, there has been a need for ratiometric fluorescent Zn(2+) probes for
      practical use. We report the rational design and synthesis of a series of
      ratiometric fluorescent Zn(2+) probes. The structures of the probes are based on
      the 7-hydroxycoumarin structure. We focused on the relationship between the
      electron-donating ability of the 7-hydroxy group and the excitation spectra of 7
      hydroxycoumarins, and exploited that relationship in the design of the
      ratiometric probes; as a result, most of the synthesized probes showed
      ratiometric Zn(2+)-sensing properties. Then, we designed and synthesized
      ratiometric Zn(2+) probes that can be excited with visible light, by choosing
      adequate substituents on coumarin dyes. Since one of the probes could permeate
      living cell membranes, we introduced the probe to living RAW264 cells and
      observed the intracellular Zn(2+) concentration via ratiometric fluorescence
      microscopy. As a result, the ratio value of the probe changed quickly in response
      to intracellular Zn(2+) concentration.

PMID- 19591461
TI  - Proton-mediated chemistry and catalysis in a self-assembled supramolecular host.
AB  - Synthetic supramolecular host assemblies can impart unique reactivity to
      encapsulated guest molecules. Synthetic host molecules have been developed to
      carry out complex reactions within their cavities, despite the fact that they
      lack the type of specifically tailored functional groups normally located in the
      analogous active sites of enzymes. Over the past decade, the Raymond group has
      developed a series of self-assembled supramolecules and the Bergman group has
      developed and studied a number of catalytic transformations. In this Account, we
      detail recent collaborative work between these two groups, focusing on chemical
      catalysis stemming from the encapsulation of protonated guests and expanding to
      acid catalysis in basic solution. We initially investigated the ability of a
      water-soluble, self-assembled supramolecular host molecule to encapsulate
      protonated guests in its hydrophobic core. Our study of encapsulated protonated
      amines revealed rich host-guest chemistry. We established that self-exchange
      (that is, in-out guest movement) rates of protonated amines were dependent on the
      steric bulk of the amine rather than its basicity. The host molecule has purely
      rotational tetrahedral (T) symmetry, so guests with geminal N-methyl groups (and
      their attendant mirror plane) were effectively desymmetrized; this allowed for
      the observation and quantification of the barriers for nitrogen inversion
      followed by bond rotation. Furthermore, small nitrogen heterocycles, such as N
      alkylaziridines, N-alkylazetidines, and N-alkylpyrrolidines, were found to be
      encapsulated as proton-bound homodimers or homotrimers. We further investigated
      the thermodynamic stabilization of protonated amines, showing that encapsulation
      makes the amines more basic in the cavity. Encapsulation raises the effective
      basicity of protonated amines by up to 4.5 pK(a) units, a difference almost as
      large as that between the moderate and strong bases carbonate and hydroxide. The
      thermodynamic stabilization of protonated guests was translated into chemical
      catalysis by taking advantage of the potential for accelerating reactions that
      take place via positively charged transition states, which could be potentially
      stabilized by encapsulation. Orthoformates, generally stable in neutral or basic
      solution, were found to be suitable substrates for catalytic hydrolysis by the
      assembly. Orthoformates small enough to undergo encapsulation were readily
      hydrolyzed by the assembly in basic solution, with rate acceleration factors up
      to 3900 compared with those of the corresponding uncatalyzed reactions.
      Furthering the analogy to enzymes that obey Michaelis-Menten kinetics, we
      observed competitive inhibition with the inhibitor NPr(4)(+), thereby confirming
      that the interior cavity of the assembly was the active site for catalysis.
      Mechanistic studies revealed that the assembly is required for catalysis and that
      the rate-limiting step of the reaction involves proton transfer from hydronium to
      the encapsulated substrate. Encapsulation in the assembly changes the
      orthoformate hydrolysis from an A-1 mechanism (in which decomposition of the
      protonated substrate is the rate-limiting step) to an A-S(E)2 mechanism (in which
      proton transfer is the rate-limiting step). The study of hydrolysis in the
      assembly was next extended to acetals, which were also catalytically hydrolyzed
      by the assembly in basic solution. Acetal hydrolysis changed from the A-1
      mechanism in solution to an A-2 mechanism inside the assembly, where attack of
      water on the protonated substrate is rate limiting. This work provides rare
      examples of assembly-catalyzed reactions that proceed with substantial rate
      accelerations despite the absence of functional groups in the cavity and with
      mechanisms fully elucidated by quantitative kinetic studies.

PMID- 19591462
TI  - A peptide-based dendrimer that enhances the splice-redirecting activity of PNA
      conjugates in cells.
AB  - The full therapeutic potential of oligonucleotide (ON)-based agents has been
      hampered by cellular delivery challenges. Cell-penetrating peptides (CPP)
      represent promising delivery vectors for nucleic acids, and their potential has
      recently been evaluated using a functional splicing redirection assay, which
      capitalizes on the nuclear delivery of splice-correcting steric-block ON
      analogues such as peptide nucleic acids (PNA). Despite encouraging in vitro and
      in vivo data with arginine-rich CPP-steric block conjugates, mechanistic studies
      have shown that entrapment within the endosome/lysosome compartment after
      endocytosis remains a limiting factor. Previous work from our group has shown
      that CPP oligomerization greatly improves cellular delivery and increases
      transfection of plasmid DNA. We now report the chemical synthesis and the
      evaluation of multivalent CPP-PNA constructs incorporating monomeric (p53(mono))
      and dendrimer-like tetrameric (p53(tet)) forms of the p53 tetramerization domain
      containing peptide, a 10 arginine CPP domain (R10), and a splice redirecting PNA
      (PNA705). These CPP-PNA conjugates were termed R10p53(tet)-PNA705 and
      R10p53(mono)-PNA705, referring to their oligomerization state. The present study
      demonstrates that the splicing redirection efficiency of PNA705 is much greater
      in the context of the tetrameric R10p53(tet)-PNA705 construct than for the
      monomeric and occurs at nanomolar concentrations, demonstrating that multivalency
      is an important factor in delivering PNA into cells.

PMID- 19591464
TI  - Porous alginate hydrogels: synthetic methods for tailoring the porous texture.
AB  - Alginate is a versatile, renewable biopolymer that has found numerous
      applications in diverse areas such as adsorbent materials of water pollutants and
      scaffolds for tissue engineering. In such kinds of applications the most
      convenient physical form of alginate-based materials is as porous matrices. The
      pore scale dimension has to be carefully engineered to meet the requirements
      posed by the specific application. The aim of this paper is to describe two
      synthetic methodologies that allow the preparation of alginate porous materials
      characterized by pores lying in well separated dimension ranges. One process is
      based on emulsion templating, which consists of dispersing an organic phase into
      an aqueous solution of alginate in the presence of a suitable emulsion stabilizer
      and locking in the structure of the continuous phase by chemical cross-linking.
      This approach required the preliminary degradation of alginate to reduce its
      molecular weight and, hence, the viscosity of the external phase of the
      concentrated emulsion. Porous matrices were characterized by pores and
      interconnects of about 10-20 and 2-5 microm, respectively, and a surface area of
      230 m(2)/g. The second process consisted of replacing the organic, internal phase
      with a gas, namely, CO(2), generated in situ the aqueous solution of alginate.
      The chemical reaction for CO(2) generation, nature of the surfactant, and cross
      linking method were carefully selected to give highly porous, stable matrices
      with pores and interconnects of the order of 300 and 80 microm, respectively.

PMID- 19591463
TI  - Self-assembled hydrogels from poly[N-(2-hydroxypropyl)methacrylamide] grafted
      with beta-sheet peptides.
AB  - A new hybrid hydrogel based on poly[N-(2-hydroxypropyl)methacrylamide] grafted
      with a beta-sheet peptide, Beta11, was designed. Circular dichroism spectroscopy
      indicated that the folding ability of beta-sheet peptide was retained in the
      hybrid system, whereas the sensitivity of the peptide toward temperature and pH
      variations was hindered. The polymer backbone also prevented the twisting of the
      fibrils that resulted from the antiparallel arrangement of the beta-strands, as
      proved by Fourier transform infrared spectroscopy. Thioflavin T binding
      experiments and transmission electron microscopy showed fibril formation with
      minimal lateral aggregation. As a consequence, the graft copolymer self-assembled
      into a hydrogel in aqueous environment. This process was mediated by association
      of beta-sheet domains. Scanning electron microscopy revealed a particular
      morphology of the network characterized by long-range order and uniformly aligned
      lamellae. Microrheology results confirmed that concentration-dependent gelation
      occurred.

PMID- 19591465
TI  - Toward an artificial Golgi: redesigning the biological activities of heparan
      sulfate on a digital microfluidic chip.
AB  - Using digital microfluidics, recombinant enzyme technology, and magnetic
      nanoparticles, we have created a functional prototype of an artificial Golgi
      organelle. Analogous to the natural Golgi, which is responsible for the enzymatic
      modification of glycosaminoglycans immobilized on proteins, this artificial Golgi
      enzymatically modifies glycosaminoglycans, specifically heparan sulfate (HS)
      chains immobilized onto magnetic nanoparticles. Sulfo groups were transferred
      from adenosine 3'-phosphate 5'-phosphosulfate to the 3-hydroxyl group of the D
      glucosamine residue in an immobilized HS chain using D-glucosaminyl 3-O
      sulfotransferase. After modification, the nanoparticles with immobilized HS
      exhibited increased affinity for fluorescently labeled antithrombin III as
      detected by confocal microscopy. Since the biosynthesis of HS involves an array
      of specialized glycosyl transferases, epimerase, and sulfotransferases, this
      approach should mimic the synthesis of HS in vivo. Furthermore, our method
      demonstrates the feasibility of investigating the effects of multienzyme systems
      on the structure of final glycan products for HS-based glycomic studies.

PMID- 19591467
TI  - Chemoselective ligation in the functionalization of polysaccharide-based
      particles.
AB  - Despite the promise of precisely targeted or otherwise functionalized polymeric
      particulate drug delivery vehicles, typical biocompatible particles are generally
      not amenable to facile and selective surface modification. Herein, we report the
      development of a simple, mild, and chemoselective strategy for the conjugation of
      biologically active molecules to the surface of dextran-based microparticles.
      Alkoxyamine-bearing reagents were used to form stable oxime conjugates with
      latent aldehyde functionality present in reducing carbohydrate chain ends. We
      demonstrate the functionalization of dextran-based microparticles with a
      fluorophore as well as a cell-penetrating peptide sequence, which facilitated the
      delivery of cargo to nonphagocytic cells leading to a 60-fold increase in the
      expression of a reporter gene when plasmid DNA-loaded particles were used.

PMID- 19591468
TI  - Probing ultrafast internal conversion through conical intersection via time
      energy map of photoelectron angular anisotropy.
AB  - The ultrafast S(2) --> S(1) internal conversion of pyrazine through a conical
      intersection of the potential energy surfaces was clearly observed by ultrafast
      photoelectron imaging. The 2D time-energy map of the photoelectron angular
      anisotropy revealed a clear signature of the internal conversion (the color
      change of green-orange-green in the horizontal direction) at approximately 0.9
      eV. The orange color at approximately 20 fs and 0.9 eV was found to correspond to
      the non-Koopmans ionization process from S(2)(pi,pi*) to D(0)(n(-1)).

PMID- 19591466
TI  - Anisotropic Fermi couplings due to large unquenched orbital angular momentum: Q
      band (1)H, (14)N, and (11)B ENDOR of bis(trispyrazolylborate) cobalt(II).
AB  - We report Q-band ENDOR of (1)H, (14)N, and (11)B at the g( parallel) extreme of
      the EPR spectrum of bis(trispyrazolylborate) cobalt(II) [Co(Tp)(2)] and two
      structural analogs. This trigonally symmetric, high-spin (hs) S = 3/2 Co(II)
      complex shows large unquenched ground-state orbital angular momentum, which leads
      to highly anisotropic electronic g-values (g( parallel) = 8.48, g( perpendicular)
      = 1.02). The large g-anisotropy is shown to result in large dipolar couplings
      near g( parallel) and uniquely anisotropic (14)N Fermi couplings, which arise
      from spin transferred to the nitrogen 2s orbital (2.2%) via antibonding
      interactions with singly occupied metal d(x(2)-y(2)) and d(z(2)) orbitals. Large,
      well-resolved (1)H and (11)B dipolar couplings were also observed. Taken in
      concert with our previous X-band ENDOR measurements at g( perpendicular) ( Myers,
      W. K.; et al. Inorg. Chem. 2008, 47, 6701-6710 ), the present data allow a
      detailed analysis of the dipolar hyperfine tensors of two of the four symmetry
      distinct protons in the parent molecule. In the substituted analogs, changes in
      hyperfine coupling due to altered metal-proton distances give further evidence of
      an anisotropic Fermi contact interaction. For the pyrazolyl 3H proton, the data
      indicate a 0.2 MHz anisotropic contact interaction and approximately 4% transfer
      of spin away from Co(II). Dipolar coupling also dominates for the axial boron
      atoms, consistent with their distance from the Co(II) ion, and resolved (11)B
      quadrupolar coupling showed approximately 30% electronic inequivalence between
      the B-H and B-C sp(3) bonds. This is the first comprehensive ENDOR study of any
      hs Co(II) species and lays the foundation for future development.

PMID- 19591469
TI  - Total synthesis of (+)-lyconadin A and related compounds via oxidative C-N bond
      formation.
AB  - The formation of carbon-nitrogen (C-N) bonds is a fundamental bond construction
      in organic synthesis and is indispensable for the synthesis of alkaloid natural
      products. In the context of the synthesis of the architecturally complex
      Lycopodium alkaloid lyconadin A, we have discovered a highly efficient oxidative
      C-N bond forming reaction that relies on the union of a nitrogen anion and a
      carbon anion. Empirical evidence amassed during our synthetic studies suggests
      that the mechanism of the C-N bond forming process encompasses polar as well as
      radical processes. Herein, we present our study of this novel C-N bond forming
      reaction and its application to the enantioselective total synthesis of lyconadin
      A and related derivatives.

PMID- 19591471
TI  - Browning of freeze-dried probiotic bacteria cultures in relation to loss of
      viability during storage.
AB  - Freeze-dried cultures of Lactobacillus acidophilus (La-5) showed visible brown
      discoloration even after a short storage at relatively mild conditions (a(w) =
      0.22 and 30 degrees C), and the browning processes were found to coincide with
      bacteria inactivation. It was demonstrated, by using high-pressure treatment for
      obtaining bacteria samples with different ratios of live/dead bacteria, that
      death of bacteria is not a prerequisite for the browning processes. Furthermore,
      it was shown that hydroxymethylfurfural (HMF) (or condensation products of HMF)
      introduces accelerated viability loss when HMF is added to the freeze-drying
      medium. Discoloration of bacteria cultures containing only sucrose/maltodextrin
      or lactose/maltodextrin in the freeze-drying matrices is suggested to be related
      to various types of nonenzymatic browning reactions, including carbonyl-protein
      (or carbonyl-DNA) interactions and carbohydrate condensation/polymerization
      (without involvement of proteins), the latter proceeding at low a(w) following
      hydrolysis of the peptidoglycan layer in the bacteria cell wall. More than one
      single type of browning reaction is accordingly concluded to be related to
      bacteria death, and the loss of viability in freeze-dried bacteria seems to be
      influenced by oxidation reactions, browning reactions, and the physical
      instability of the bacteria membrane/cell wall.

PMID- 19591470
TI  - Palladium-catalyzed coupling of ammonia with aryl chlorides, bromides, iodides,
      and sulfonates: a general method for the preparation of primary arylamines.
AB  - We report that the complex generated from Pd[P(o-tol)(3)](2) and the
      alkylbisphosphine CyPF-t-Bu is a highly active and selective catalyst for the
      coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The
      couplings of ammonia with this catalyst conducted with a solution of ammonia in
      dioxane form primary arylamines from a variety of aryl electrophiles in high
      yields. Catalyst loadings as low as 0.1 mol % were sufficient for reactions of
      many aryl chlorides and bromides. In the presence of this catalyst, aryl
      sulfonates also coupled with ammonia for the first time in high yields. A
      comparison of reactions in the presence of this catalyst versus those in the
      presence of existing copper and palladium systems revealed a complementary, if
      not broader, substrate scope. The utility of this method to generate amides,
      imides, and carbamates is illustrated by a one-pot synthesis of a small library
      of these carbonyl compounds from aryl bromides and chlorides, ammonia, and acid
      chlorides or anhydrides. Mechanistic studies show that reactions conducted with
      the combination of Pd[P(o-tol)(3)](2) and CyPF-t-Bu as catalyst occur with faster
      rates and higher yields than those conducted with CyPF-t-Bu and palladiun(II) as
      catalyst precursors because of the low concentration of active catalyst that is
      generated from the combination of palladium(II), ammonia, and base.

PMID- 19591472
TI  - Photolysis of chlortetracycline on a clay surface.
AB  - Chlortetracycline, an antibiotic commonly used as a growth promoter in livestock,
      enters the environment primarily through application of animal waste to open
      fields. The photochemical loss of chlortetracycline in sunlight-exposed soils is
      a potentially important process in its environmental fate, especially because it
      is photochemically labile and sorbs strongly to mineral surfaces. In this study,
      photolysis on kaolinite clay under simulated sunlight was used as a model system
      to elucidate the mechanistic kinetics of chlortetracycline photolysis on soil
      surfaces. The results suggest that photolysis may be an important loss process
      for chlortetracycline sorbed to sunlight-exposed soils, as well as to suspended
      clays in surface waters. Under direct irradiation equivalent to noon-time, summer
      sunlight in the midwestern United States, chlortetracycline at the outer clay
      surface (before light attenuation) degraded with a rate constant of k(0)(p) =
      0.65 +/- 0.30 h(-1). The depth at which photochemical action was reduced by 50%
      (z(0.5)), one of the parameters of the mechanistic model, was found to be 0.014
      +/- 0.004 mm. The quantum yield on the clay surface was estimated to be (1.3 +/-
      0.7) x 10(-4), an order of magnitude lower than the quantum yield of the aqueous
      chlortetracycline zwitterion [(1.3 +/- 0.3) x 10(-3); pH 5], although still
      significant.

PMID- 19591473
TI  - Separation of phthalocyanine-like substances from humic acids using a molecular
      imprinting method and their photochemical activity under simulated sunlight
      irradiation.
AB  - To elucidate the existence of phthalocyanine-like (Pc-like) substances in humic
      acids (HA) and their roles in photochemical transformation of organic pollutants,
      Pc-imprinted polymers (MIP) were synthesized successfully and employed to
      separate Pc-like substances from HA. The fraction bound by MIP (F(mip-b))
      presented better photochemical activity for degradation of 2,4
      dichlorophenoxyacetic acid (2,4-D) in aqueous solution irradiated by simulated
      sunlight. The pseudo-first-order rate constant of 2,4-D photodegradation with the
      presence of F(mip-b) was 2.5 times as high as that in solution containing
      effluent fraction (F(eff)). These results show the key role of some HA with
      special structures in photochemistry and are helpful for better understanding
      phototransformation of environmental contaminants in natural aquatic systems.

PMID- 19591474
TI  - Clarification of the stereochemical course of nucleophilic substitution of
      arylsulfonate-based nucleophile assisting leaving groups.
AB  - Secondary alcohols modified as tosylates, PEG-sulfonates, or quisylates undergo
      inversion of configuration at the reacting center when treated with lithium
      halide in acetone at reflux, where the PEG-sulfonates and quisylates are
      substantially more reactive. In sterically hindered cases, elimination is a
      competing process. In contrast, when treated with TiCl(4), simple secondary
      sulfonates give chloride products with partial inversion of configuration. Any
      observed retention of configuration in a given alkyl sulfonate substrate under
      these conditions is likely due to neighboring group participation or
      diastereoselective attack on a carbocation (or ion pair) rather than an S(N)i
      mechanism.

PMID- 19591475
TI  - Computed rate coefficients and product yields for c-C5H5 + CH3 --> products.
AB  - Using quantum chemical methods, we have explored the region of the C6H8 potential
      energy surface that is relevant in predicting the rate coefficients of various
      wells and major product channels following the reaction between cyclopentadienyl
      radical and methyl radical, c-C5H5 + CH3. Variational transition state theory is
      used to calculate the high-pressure-limit rate coefficient for all of the
      barrierless reactions. RRKM theory and the master equation are used to calculate
      the pressure dependent rate coefficients for 12 reactions. The calculated results
      are compared with the limited experimental data available in the literature and
      the agreement between the two is quite good. All of the rate coefficients
      calculated in this work are tabulated and can be used in building detailed
      chemical kinetic models.

PMID- 19591476
TI  - Two reactivity modes in the heterogeneous cyclohexene ozonolysis under
      tropospherically relevant ozone-rich and ozone-limited conditions.
AB  - Important mechanistic differences regarding C=C double-bond oxidation processes
      under ozone-limited and ozone-rich reaction conditions for cyclohexene
      functionalized fused silica substrates serving as model systems for studying
      heterogeneous C=C double bond oxidation chemistry in the troposphere are
      evaluated. By using broadband vibrational sum frequency generation (SFG), we
      track heterogeneous ozone reactions in real time. Ozone levels span three orders
      of magnitude and represent environments ranging from pristine remote continental
      regions to highly polluted urban centers, ranging from 30 ppb to 3 ppm (from 7 x
      10(11) molecules cm(-3) to 7 x 10(13) molecules cm(-3)). We determine reaction
      rates and reactive uptake coefficients (gamma values). At these tropospherically
      relevant ozone levels, the heterogeneous reaction rates follow a Langmuir
      Hinshelwood-type mechanism. The product formation rates, which we determine as a
      function of ozone concentrations, are found to be half of the olefin reaction
      rates. This ratio is consistent with the previously proposed reaction pathway
      involving the breaking of one C=C double bond containing two olefinic CH moieties
      to form a product containing only one methyl group and one polar carbonyl moiety.
      Contact angle histograms show that out of a total of 60 measurements, there are
      about 25 more measurements with contact angles up to ten degrees below the mean
      recorded prior to reaction when ozone levels resemble remote continental
      conditions (50 ppb) than when ozone levels resemble urban conditions (1 ppm). The
      implication of these results are that the methyl formation pathway in
      heterogeneous ozonolysis may be less favorable than the carboxylic acid- and
      secondary ozonide-production pathway for ozone-limited conditions (i.e., in the
      remote continental troposphere or during urban nighttime) as opposed to ozone
      rich (i.e., polluted urban atmosphere) conditions.

PMID- 19591477
TI  - Bronsted sites on acid-treated montmorillonite: a theoretical study with probe
      molecules.
AB  - The effect of isomorphic substitution on Bronsted acid sites, generated during
      acid treatment of montmorillonite, was studied using the density functional
      theory (DFT) and the cluster model method. Cluster models describing acid
      montmorillonite were constructed and used as a matrix for the protonation of
      several test molecules under different types of isomorphic substitution. Our
      results concerning geometries, energies, and infrared vibrational frequencies
      indicate that isomorphic substitution of aluminum with magnesium in the
      octahedral sheet leads to stronger acid sites and more effective protonation of
      test molecules than those produced by substitution of silicon with aluminum in
      the tetrahedral sheet.

PMID- 19591478
TI  - Factors affecting copper(II) binding to multiarmed cyclam-grafted mesoporous
      silica in aqueous solution.
AB  - Single- as well as multi-anchored cyclam-functionalized silica samples have been
      prepared by grafting amorphous silica gel (K60) and mesostructured silica (SBA
      15) with silylated cyclam precursors bearing one, two, or four triethoxysilyl
      groups, respectively ascribed to cyclam-mono, cyclam-di, and cyclam-tetra. Their
      reactivity toward copper(II) has been thoroughly investigated in aqueous solution
      and discussed with respect to the number of arms tethering the ligand to the
      silica surface and the structural ordering of the adsorbent in terms of capacity,
      long-term stability, and speed of access to the binding sites. Less-than-complete
      metal ion uptake was always observed, even in excess of cyclam groups with
      respect to solution-phase Cu(II), suggesting lower stability of immobilized
      complexes relative to those in solution. Therefore, the number of arms attaching
      cyclam moieties to the silica walls (one, two, or four) was found to dramatically
      affect the binding properties of these hybrids toward copper(II), revealing
      significantly larger capacities when reducing the number of arms (less rigidity
      constraints in the macrocycle). In parallel, multiarm tethering resulted in
      better chemical resistance toward degradation as evidenced by UV-visible
      monitoring of Cu-cyclam complexes in solution (i.e., more ligand leaching from
      the adsorbent for singly tethered cyclam). On the other hand, electron spin
      resonance (ESR) experiments did not evidence significant differences between
      complexes bearing one, two, or four alkyl arms, since all Cu(II)-cyclam surface
      complexes were found to be hexacoordinated with a strong equatorial ligand field.
      Comparison of amorphous gels and mesostructured materials indicates that the
      binding properties of the adsorbents were hardly influenced by their level of
      ordering, suggesting that accessibility to the binding sites was not the limiting
      factor. Some advantage belonging to mesostructured adsorbents was however
      observed with respect to the rate of access to the active centers at pH values
      close to neutrality (due to faster mass transport), but this was no more the case
      when operating at lower pH values where the formation of the Cu-cyclam complex
      became the rate-determining step, as pointed out by electrochemistry.

PMID- 19591479
TI  - Monitoring and mapping imperfections in silane-based self-assembled monolayers by
      chemical amplification.
AB  - This paper describes an innovative and simple technique for analyzing defects in
      silane-based self-assembled monolayers. The assembly of monolayers is a simple
      method for chemically modifying surfaces, which can be important for resisting
      chemical attack or adhesion of biomolecules. Measuring the molecular scale
      properties of monolayers and the reproducibility of their ability to uniformly
      modify a surface requires tools that provide limits of detection at the level of
      at least a few atoms per million with specificity to the top couple nanometers of
      the surface. To achieve this level of sensitivity a new technique is developed
      that combines spectroscopy and microscopy techniques (particularly atomic force
      microscopy) with chemical amplification of exposed silicon in self-assembled
      monolayers of silane molecules. This development is an important achievement for
      monitoring the quality of monolayers as a function of modifications to the
      method(s) used to deposit the silane molecules. Techniques presented here could
      be easily extended to assessing the molecular scale quality of other surface
      modifications.

PMID- 19591480
TI  - Highly controlled silica coating of PEG-capped metal nanoparticles and
      preparation of SERS-encoded particles.
AB  - Thiol-modified poly(ethylene glycol) (mPEG-SH) has been used to replace standard
      capping agents from the surfaces of gold nanoparticles with different sizes and
      shapes. Upon PEG stabilization, the nanoparticles can be transferred into
      ethanol, where silica can be directly grown on the particle surfaces through the
      standard Stober process. The obtained silica shells are uniform and homogeneous,
      and the method allows a high degree of control over shell thickness for any
      particle size and shape. Additionally, Raman-active molecules can be readily
      incorporated within the composite nanoparticles during silica growth so that
      SERS/SERRS-encoded nanoparticles can be fabricated containing a variety of tags,
      thereby envisaging multiplexing capability.

PMID- 19591481
TI  - Interfacial water at hydrophobic and hydrophilic surfaces: slip, viscosity, and
      diffusion.
AB  - The dynamics and structure of water at hydrophobic and hydrophilic diamond
      surfaces is examined via non-equilibrium Molecular Dynamics simulations. For
      hydrophobic surfaces under shearing conditions, the general hydrodynamic boundary
      condition involves a finite surface slip. The value of the slip length depends
      sensitively on the surface water interaction strength and the surface roughness;
      heuristic scaling relations between slip length, contact angle, and depletion
      layer thickness are proposed. Inert gas in the aqueous phase exhibits pronounced
      surface activity but only mildly increases the slip length. On polar hydrophilic
      surfaces, in contrast, slip is absent, but the water viscosity is found to be
      increased within a thin surface layer. The viscosity and the thickness of this
      surface layer depend on the density of polar surface groups. The dynamics of
      single water molecules in the surface layer exhibits a similar distinction: on
      hydrophobic surfaces the dynamics is purely diffusive, while close to a
      hydrophilic surface transient binding or trapping of water molecules over times
      of the order of hundreds of picoseconds occurs. We also discuss in detail the
      effect of the Lennard-Jones cutoff length on the interfacial properties.

PMID- 19591482
TI  - Color properties and structural phase transition in penta- and hexacoordinate
      isothiocyanato Ni(II) compounds.
AB  - We investigated the optical properties of (NBu(4))(3)[Ni(NCS)(5)], a
      pentacoordinate Ni compound, and compared the results with the more traditional
      hexacoordinate analogue (NEt(4))(4)[Ni(NCS)(6)]. On the basis of our
      complementary electronic structure calculations, the color properties of this
      high spin complex can be understood in terms of excitations between strongly
      hybridized orbitals with significant Ni d and ligand character. Variable
      temperature vibrational studies show mode softening with decreasing temperature
      and splitting near 200 K, trends that we attribute to improved low temperature
      intermolecular interactions and a weak structural phase transition, respectively.

PMID- 19591483
TI  - Star polymers via cross-linking amphiphilic macroinitiators by AGET ATRP in
      aqueous media.
AB  - Amphiphilic star polymers with low polydispersity (PDI) and high molecular weight
      were synthesized by an activator generated by electron transfer atom transfer
      radical polymerization (AGET ATRP) in aqueous dispersed media using a simple "arm
      first" method and linear block copolymers poly(ethylene oxide)-b-polystyrene (PEO
      PS-Cl) as arm precursors. The amphiphilic block copolymers PEO-PS-Cl with halogen
      chain-end functionality formed micelles in water and then were cross-linked by
      the divinyl cross-linkers. Due to the formation of cross-linker swollen micelles
      before the polymerization was initiated, star-star or star-linear chain reactions
      were not required for the star formation. The suppressed star-star coupling
      reactions resulted in the formation of star polymers with low PDI (M(w)/M(n) <
      1.1) but still high molecular weight (over 1000 kg/mol).

PMID- 19591484
TI  - Metabolomic insight into soy sauce through (1)H NMR spectroscopy.
AB  - Soy sauce, a well-known seasoning in Asia and throughout the world, consists of
      many metabolites that are produced during fermentation or aging and that have
      various health benefits. However, their comprehensive assessment has been limited
      due to targeted or instrumentally specific analysis. This paper presents for the
      first time a metabolic characterization of soy sauce, especially that aged up to
      12 years, to obtain a global understanding of the metabolic variations through
      (1)H NMR spectroscopy coupled with multivariate pattern recognition techniques.
      Elevated amino acids and organic acids and the consumption of carbohydrate were
      associated with continuous involvement of microflora in aging for 12 years. In
      particular, continuous increases in the levels of betaine were found during aging
      for up to 12 years, demonstrating that microbial- or enzyme-related metabolites
      were also coupled with osmotolerant or halophilic bacteria present during aging.
      This work provides global insights into soy sauce through a (1)H NMR-based
      metabolomic approach that enhances the current understanding of the holistic
      metabolome and allows assessment of soy sauce quality.

PMID- 19591485
TI  - Synthesis, in vivo evaluation, and molecular modeling studies of new pyrazolo[5,1
      c][1,2,4]benzotriazine 5-oxide derivatives. Identification of a bifunctional
      hydrogen bond area related to the inverse agonism.
AB  - A new series of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-alkyloxy-/aryloxy
      /arylalkyloxy and 8-aryl-/arylalkylderivatives variously substituted at the 3
      position were synthesized and binding studies at the benzodiazepine site on
      GABA(A) receptor were carried out. The pharmacological profile was identified for
      compounds 10, 11, 16(+), 16(-), and 17 by considering six potential
      benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous
      motility and explorative activity, potential anxiolytic-like effects, mouse
      learning and memory modulation, and finally, ethanol-potentiating action.
      Compound 17 stands out as the compound that improves mouse memory processes
      selectively, safely, and in a statistically significant manner. From a ligand
      based pharmacophoric model, we identified a hydrogen bond interaction area HBp-3
      near the lipophilic area. This new pharmacophoric model allowed us to identify
      four structural compound typologies and thus to rationalize the affinity data of
      all compounds.

PMID- 19591486
TI  - Cyclic minigastrin analogues for gastrin receptor scintigraphy with technetium
      99m: preclinical evaluation.
AB  - Two cyclized minigastrin analogues for gastrin receptor scintigraphy were
      synthesized and derivatized with HYNIC at the N-terminus for labeling with 99mTc.
      Radiolabeling efficiency, stability, cell internalization, and receptor binding
      on CCK-2 receptor expressing AR42J cells were studied and the biodistribution
      evaluated in tumor bearing nude mice, including NanoSPECT/CT imaging. Metabolites
      in urine, liver, and kidneys were analyzed by radio-HPLC. Radiolabeled cyclic MG
      showed high stability in vitro and receptor mediated uptake in AR42J cells. In
      the animal tumor model, fast renal clearance and low nonspecific uptake in most
      organs were observed. A tumor uptake >3% was calculated ex vivo 1 h p.i. for both
      99mTc-EDDA-HYNIC-cyclo-MG1 and 99mTc-EDDA-HYNIC-cyclo-MG2. In an imaging study
      with 99mTc-EDDA-HYNIC-cyclo-MG1, the tumor was clearly visualized. The metabolite
      analysis indicated rapid enzymatic degradation in vivo.

PMID- 19591487
TI  - 3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha
      mitogen activated protein kinase and casein kinase 1delta.
AB  - In this study, we report on the discovery of isoxazole 1 as a potent dual
      inhibitor of p38alpha (IC(50) = 0.45 microM) and CK1delta (IC(50) = 0.23 microM).
      Because only a few effective small molecule inhibitors of CK1 have been described
      so far, we aimed to develop this structural class toward specific agents.
      Molecular modeling studies comparing p38alpha/CK1delta suggested an optimization
      strategy leading to design, synthesis, biological characterization, and SAR of
      highly potent compounds including 9 (IC(50) p38alpha = 0.006 microM; IC(50)
      CK1delta = 1.6 microM), 13 (IC(50) p38alpha = 2.52 microM; IC(50) CK1delta =
      0.033 microM), 17 (IC(50) p38alpha = 0.019 microM; IC(50) CK1delta = 0.004
      microM; IC(50) CK1epsilon = 0.073 microM), and 18 (CKP138) (IC(50) p38alpha =
      0.041 microM; IC(50) CK1delta = 0.005 microM; IC(50) CK1epsilon = 0.447 microM)
      possessing differentiated specificity. Selected compounds were profiled over 76
      kinases and evaluation of their cellular efficacy showed 18 (CKP138) to be a
      highly potent and dual-specific inhibitor of CK1delta and p38alpha.

PMID- 19591488
TI  - Synthesis and biological evaluation of guanidino compounds endowed with
      subnanomolar affinity as competitive inhibitors of maize polyamine oxidase.
AB  - Previous studies on agmatine and its derivatives suggested that the presence of
      hydrophobic groups on the guanidine moiety was a crucial key for inhibitory
      activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and
      iminoctadine derivatives were synthesized and tested for their ability to inhibit
      this enzyme. Several compounds showed an affinity in the nanomolar range, while a
      cyclopropylmethyl derivative of iminoctadine was found to be the most potent
      inhibitor of maize polyamine oxidase reported so far (Ki = 0.08 nM).

PMID- 19591490
TI  - Thin film assemblies of molecularly-linked metal nanoparticles and
      multifunctional properties.
AB  - The use of metal nanoparticles as building blocks toward thin film assembly
      creates intriguing opportunities for exploring multifunctional properties. Such
      an exploration requires the ability to engineer the size, shape, composition, and
      especially interparticle properties in nanoparticle assemblies for harnessing the
      collective properties of the nanoscale building blocks. This article highlights
      some of the important findings of our investigations of thin film assemblies of
      molecularly linked nanoparticles for exploiting their multifunctional and
      collective properties in molecular recognition and chemical sensing. The
      thermally activated processing approach presents a viable pathway for
      nanoengineering metal, alloy, and core-shell nanoparticles as building blocks.
      The molecular mediator-templating approach offers an effective strategy to thin
      film assemblies of the nanoscale building blocks that impart multifunctional
      properties. In such thin film assemblies, the interparticle interactions and
      structures dictate the correlation between the nanostructural parameters and the
      optical and electrical properties. By highlighting selected examples involving
      ligand-framework binding of ionic species at the film/liquid interface and
      electrical responses to molecular sorption at the film/gas interface, the
      multifunctional properties of the thin film assemblies are further discussed in
      terms of interparticle covalent, hydrogen bonding, ionic, or van der Waals
      interactions in a framework-type architecture for the creation of molecular
      recognition and chemical sensing sites that can be tuned chemically or
      electrochemically. Implications of these insights to expanding the exploration of
      nanoparticle thin film assemblies for a wide range of technological applications
      are also discussed.

PMID- 19591489
TI  - Age-dependent modifications of the human salivary secretory protein complex.
AB  - Physiological variability of the naturally occurring, human salivary secretory
      peptidome was studied as a function of age. The qualitative and quantitative
      changes occurring in the secretion of proteins/peptides specific to the oral
      cavity (i.e., basic salivary proline-rich proteins, salivary acidic proline-rich
      phosphoproteins, statherin, proline-rich peptide P-B, salivary cystatins, and
      histatins) were investigated by high-performance liquid chromatography
      electrospray ionization-mass spectrometry in 67 subjects aged between 3 and 44
      years. Subjects were divided into five age groups: group A, 8 donors, 3-5 years;
      group B, 11 donors, 6-9 years; group C, 20 donors, 10-12 years; group D, 15
      donors, 13-17 years; group E, 13 donors, 24-44 years. Basic salivary proline-rich
      proteins, almost undetectable in the 3-5 and 6-9 years groups, reached salivary
      levels comparable to that of adults (24-44 years) around puberty. Levels of
      peptide P-D, basic peptide P-F, peptide P-H, peptide P-J (a new basic salivary
      proline-rich protein characterized in this study), and basic proline-rich peptide
      IB-1 were significantly higher in the 10-12-year-old group than in the 3-5-year
      old group, whereas the increase of proline-rich peptide II-2 was significant only
      after the age of 12 years. The concentration of salivary acidic proline-rich
      phosphoproteins, histatin-3 1/24, histatin-3 1/25, and monophosphorylated and
      diphosphorylated cystatin S showed a minimum in the 6-9-year-old group. Finally,
      the histatin-1 concentration was significantly higher in the youngest subjects (3
      5 years) than in the other groups.

PMID- 19591491
TI  - Ion flotation of Co2+, Ni2+, and Cu2+ using dodecyldiethylenetriamine (Ddien).
AB  - Ion flotation is a separation process involving the adsorption of a surfactant
      and counterions at an air/aqueous solution interface. It shows great promise for
      removing toxic heavy metal ions from dilute aqueous solutions. It was found that
      a chelating surfactant, dodecyldiethylenetriamine (Ddien), could selectively
      remove one metal ion over others at different pH values. Selectivity was
      attributed to the formation of surface-active chelated species at specific pH.
      Surface tension data show that [M-(Ddien)2]2+ is more surface-active than [M
      (Ddien)]2+ and other Ddien species, thus the relative fraction of [M-(Ddien)2]2+
      in the solution determined the metal ion flotation efficiency. The ion flotation
      results were consistent with the surface tension data and the relevant speciation
      diagrams. Theoretical discussion reveals that DeltaG0ads and DeltaG0chelation for
      the Ni(II) and Co(II) ions in the Ddien-Ni(II) and Ddien-Co(II) systems are more
      negative than those for Cu(II) in the Ddien-Cu(II) system.

PMID- 19591492
TI  - Rapid and enantioselective assembly of the lycorine framework using
      chemoenzymatic techniques.
AB  - The pentacyclic framework associated with the alkaloid (-)-lycorine (1) can be
      assembled in as few as six steps from the enantiomerically pure cis-1,2
      dihydrocatechol 3 which is itself readily available on a large scale through the
      whole-cell biotransformation of bromobenzene. The methodology has been used in
      developing the first synthesis of compound 2, a derivative of lycorine.

PMID- 19591493
TI  - Grafting of poly(acrylic acid) onto an aluminum surface.
AB  - Grafting of poly(acrylic acid) (PAA) onto an aluminum surface was successfully
      achieved by free radical polymerization of acrylic acid using typical radical
      initiators, benzoyl peroxide and 2,2'-azobisisobutyronitrile. Both spotlike and
      brush morphologies were achieved. A complete coverage of PAA on an aluminum
      surface was then achieved by using a thermal chemical vapor deposition process.
      The PAA thickness was determined by ellipsometry and the superficial chemical
      composition by X-ray photoelectron spectroscopy (XPS). Grazing angle Fourier
      transform infrared (FTIR) spectroscopy confirmed the presence of carboxylic acid
      groups on the surface, and the contact angle measurements revealed a decreasing
      free surface energy of aluminum due to the polymer surface covering.

PMID- 19591494
TI  - Domains in ferroelectric nanodots.
AB  - Almost free-standing single crystal mesoscale and nanoscale dots of ferroelectric
      BaTiO(3) have been made by direct focused ion beam patterning of bulk single
      crystal material. The domain structures which appear in these single crystal
      dots, after cooling through the Curie temperature, were observed to form into
      quadrants, with each quadrant consisting of fine 90 degrees stripe domains. The
      reason that these rather complex domain configurations form is uncertain, but we
      consider and discuss three possibilities for their genesis: first, that the
      quadrant features initially form to facilitate field-closure, but then develop 90
      degrees shape compensating stripe domains in order to accommodate disclination
      stresses; second, that they are the result of the impingement of domain packets
      which nucleate at the sidewalls of the dots forming "Forsbergh" patterns
      (essentially the result of phase transition kinetics); and third, that 90 degrees
      domains form to conserve the shape of the nanodot as it is cooled through the
      Curie temperature but arrange into quadrant packets in order to minimize the
      energy associated with uncompensated surface charges (thus representing an
      equilibrium state). While the third model is the preferred one, we note that the
      second and third models are not mutually exclusive.

PMID- 19591495
TI  - Direct imaging of soft-hard interfaces enabled by graphene.
AB  - Direct imaging of surface molecules and the interfaces between soft and hard
      materials on functionalized nanoparticles is a great challenge using modern
      microscopy techniques. We show that graphene, a single atomic layer of sp(2)
      bonded carbon atoms, can be employed as an ultrathin support film that enables
      direct imaging of molecular layers and interfaces in both conventional and atomic
      resolution transmission electron microscopy. An atomic-resolution imaging study
      of the capping layers and interfaces of citrate-stabilized gold nanoparticles is
      used to demonstrate this novel capability. Our findings reveal the unique
      potential of graphene as an ideal support film for atomic-resolution transmission
      electron microscopy of hard and soft nanomaterials.

PMID- 19591498
TI  - Interactions of Cl- and OH radical in aqueous solution.
AB  - There is a considerable controversy surrounding the nature of the Cl-/OH complex
      in aqueous solution, which appears as a byproduct of the irradiation of salt
      solutions in nuclear reactor operation, radioactive waste storage, medicine, and
      environmental problems. In this work, we report results of combined quantum
      mechanical molecular mechanics calculations of ground-state free-energy surfaces
      and absorption spectrum through the CCSDT level of theory that are consistent
      with the experimental data and suggest that hemibonded HOCl- species may indeed
      exist in bulk aqueous solution.

PMID- 19591497
TI  - Hydrogen abstraction by chlorine atom from small organic molecules containing
      amino acid functionalities: an assessment of theoretical procedures.
AB  - A high-level quantum chemistry investigation has been carried out for the
      abstraction by chlorine atom of hydrogen from methane and five monosubstituted
      methanes, chosen to reflect the chemical functionalities contained in amino acids
      and peptides. A modified W1' procedure is used to calculate benchmark barriers
      and reaction energies for the six reactions. The reactions demonstrate a broad
      range of barrier heights and reaction energies, which can be rationalized using
      curve-crossing and molecular orbital theory models. In addition, the performance
      of a range of computationally less demanding electronic structure methods is
      assessed for calculating the energy profiles for the six reactions. It is found
      that the G3X(MP2)-RAD procedure compares best with the W1' benchmark,
      demonstrating a mean absolute deviation (MAD) from W1' of 2.1 kJ mol(-1). The
      more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to
      perform well, with MADs from W1' of 2.9 and 3.0 kJ mol(-1), respectively.

PMID- 19591499
TI  - Infrared spectra and density functional calculations for SMO2 molecules (M = Cr,
      Mo, W).
AB  - Infrared absorptions of the matrix isolated SMO2 (M = Cr, Mo, W) molecules were
      observed following laser-ablated metal atom reactions with SO2 during
      condensation in solid argon and neon. The symmetric and antisymmetric M-O
      stretching mode assignments were confirmed by appropriate S18O2 and S(16,18)O2
      isotopic shifts. The much weaker Cr-S stretching mode was identified through its
      34S shift. Density functional (B3LYP and BPW91) calculations were performed to
      obtain molecular structures and to reproduce the infrared spectra. Computed
      pyramidal structures for the SMO2 molecules are very similar to those for the
      analogous trioxides and this functional group in [MO2S(bdt)]2- complexes.
      Additional weaker absorptions are assigned to the (SO2)(SMO2) adducts, which are
      stabilized by a four-membered ring.

PMID- 19591500
TI  - Two-body dissociative charge exchange dynamics of sym-triazine.
AB  - Translational spectroscopy coupled with coincidence detection techniques has been
      used to investigate the two-body dissociation of sym-triazine to HCN + (HCN)2
      upon electronic excitation from charge exchange between the sym-triazine cation
      and cesium. This dissociation mechanism was determined to occur after excitation
      of sym-triazine into the 3s Rydberg electronic manifold, and the observed
      dynamics suggest that the mechanism competes with a stepwise three-body
      dissociation mechanism to three HCN products that occurs from this same
      electronic excitation. On the basis of reported stabilization energies of several
      isomers of the HCN dimer, possible structures of the metastable (HCN)2 species
      are discussed in light of the current measurements.

PMID- 19591501
TI  - Influence of water in the UV-induced chemistry of methanol in the solid phase.
AB  - UV-irradiated methanol (CH3OH) in water ice at 3 K has been investigated with
      infrared spectroscopy and compared with pure methanol. The main byproducts
      detected are formaldehyde (H2CO), carbon monoxide (CO), carbon dioxide (CO2),
      methane (CH4), and ethylene glycol (C2H4(OH)2). The production of H2CO, CO2, and
      CO is enhanced in water ice, resulting from cross reactions between the
      byproducts of methanol with those of water (OH and H2O2).

PMID- 19591502
TI  - Coordination of (glycyl)(n)glycine (n = 1-3) to Co+ and Co2+.
AB  - This paper analyses the interaction of Co+ (d8, 1G, and 3F) and Co2+ (d7, 4F)
      cations with (glycyl)(n)glycine (n = 1-3) oligomers. The structure, relative
      energies, and binding energies of the complexes formed have been theoretically
      determined by means of density functional methods. For all Co+ complexes the
      ground spin state is the triplet one and the most stable structures show
      tricoordinated geometries. In contrast, for Co2+ systems the lowest energy
      structures are tricoordinated (n = 1), tetracoordinated (n = 2), and
      pentacoordinated (n = 3). For both cobalt cations, interaction energies increase
      with the peptide length. Differences in the coordination properties of the
      ligands are discussed according to their length as well as to the electronic
      configuration of the metal cation, and results are compared to those previously
      obtained for the analogous Cu(+/2+) systems. The IR spectra of the most stable
      and low energy conformers have been simulated, and a discussion of the main
      vibrational features is provided.

PMID- 19591503
TI  - Atomic alignment effects for the formation of excimers RgX* (B, C) in the
      reaction of oriented Rg ((3)P2, M(J) = 2) (Rg = Xe, Kr, Ar) + halogen(X)
      containing molecules.
AB  - Atomic alignment effects for the formation of excimers, RgX* (B, Omega = 1/2) and
      RgX* (C, Omega = 3/2), in the reaction of Rg ((3)P(2)) (Rg = Xe, Kr, Ar) with
      halogen (X)-containing molecules (RX) (CH(3)I, CF(3)I, CF(3)Br, NF(3), CHBr(3),
      CHCl(3), CCl(3)F, and CCl(4)) have been measured by using an oriented Rg
      ((3)P(2), M(J) = 2) atomic beam at a collision energy of approximately 0.07 eV.
      The emission intensities for RgX* (B, C) have been measured as a function of the
      magnetic orientation field direction in the collision frame. The reactant (RX)
      dependence of the atomic alignment effect is extremely different between the RgX*
      (B) and the RgX* (C) channels. For RgX* (C), an analogous atomic alignment effect
      is commonly observed despite the difference of RX and Rg. In contrast, for RgX*
      (B), the atomic alignment effect shows a diverse dependence on RX and Rg.

PMID- 19591505
TI  - Efficient red-edge materials photosensitized by Rhodamine 640.
AB  - We report on tunable, highly efficient and photostable solid-state dye laser
      emitting around 640 nm based on Rhodamine 640 incorporated into homopolymers,
      linear and cross-linked copolymers, and silicon-modified organic matrices. The
      effect on the lasing properties of both dye concentration and environmental
      conditions was analyzed. Under transversal pumping at 532 nm with 5.5 mJ/pulse,
      high-lasing efficiencies of up to 42% were recorded. The laser operation was
      highly stable with a drop in the laser output of approximately 20% after 100 000
      pump pulses at the same position of the sample at 10 Hz repetition rate. To the
      best of our knowledge, these results are the topmost achieved to date for
      organic, inorganic, and hybrid materials doped with rhodamine 640. When the
      samples were incorporated into a grazing-incidence grating oscillator, narrow
      line-width operation with tunning ranges of up to 40 nm was obtained.

PMID- 19591504
TI  - Size-specific concentration of DNA to a nanostructured tip using
      dielectrophoresis and capillary action.
AB  - One of the critical challenges in the fields of disease diagnostics and
      environmental monitoring is to concentrate extracellular DNA from a sample
      mixture rapidly. Unlike genomic DNA in normal cells, extracellular DNA dissolved
      in a biological sample can potentially offer crucial information about pathogens
      and toxins. The current concentration methods, however, are not able to directly
      concentrate extracellular DNA due to aggressive sample preparation steps. This
      paper presents a concentration mechanism of extracellular DNA onto a
      nanostructured tip using dielectrophoresis (DEP) in conjunction with capillary
      action. DNA immersed in a solution is captured onto a nanotip by two sequential
      actions: (1) attraction of DNA and other bioparticles in the vicinity of a
      nanotip by DEP and (2) size-specific capture of DNA onto the nanotip by capillary
      action. To investigate the size-specific capturing mechanism, an analytical model
      for the capillary action on a nanotip is presented, which is compared to the
      experiment for capturing polystyrene nanospheres. This analysis predicts the
      capture of a spherical particle smaller than 0.39 times a nanotip diameter,
      whereas our experiment shows that polystyrene spheres smaller than 0.84 times a
      nanotip diameter are captured. This discrepancy can be caused by the increase of
      the capturing force due to attractive DEP force. In addition, the diameter of the
      captured spheres can be increased by other experimental conditions including the
      tip geometry, the multiple particle interaction, and the contact angles. When a
      nanotip is used for concentrating lambda-DNA, 6.7 pg/mL (210 aM) of DNA is
      selectively extracted from a sample mixture containing lambda-DNA and Drosophila
      cells in one minute. The captured DNA is investigated by fluorescence microscopy,
      scanning electron microscopy (SEM), and X-ray analysis. This nanotip-based DNA
      concentrating method is a rapid and highly sensitive technique to detect
      extracellular DNA from a sample mixture.

PMID- 19591506
TI  - Reversible quantum confinement of polarons by reaction of protonated emeraldine
      with nitric oxide.
AB  - Nitric oxide (NO), a free radical, adds to green emeraldine acid, a polyradical
      and a one-dimensional polaronic conductor. As more NO is added, the segments
      through which protons and their associated unpaired electrons move, i.e., the
      polarons, are progressively shortened. This confinement of polarons is observed
      as a spectral progression from the parent green emeraldine acid, with an
      absorption maximum at 875 nm, to a series of blue polymers, their absorption
      maxima shifting progressively while decreasing in intensity with NO uptake to 670
      nm, then turning colorless, with only a faint residual absorption at lambda (max)
      = 625 nm for the end member of the series which is insulating and no longer shows
      a voltammetric wave. The sequence is reversed in dilute HCl where the colorless
      and insulating polymer releases nitric oxide, the polaron is deconfined and the
      voltammetric wave reappears.

PMID- 19591508
TI  - Spatial control of 3D energy transfer in supramolecular nanostructured host-guest
      architectures.
AB  - Systematic control of 3D energy transfer (ET) dynamics is achieved in
      supramolecular nanostructured host-guest systems using spacer-functionalized
      guest chromophores. Quantum chemistry-based Monte Carlo simulations reveal the
      strong impact of the spacer length on the ET dynamics, efficiency, and
      dimensionality. Remarkably high exciton diffusion lengths demonstrate that there
      is ample scope for optimizing oligomeric or polymeric optoelectronic devices.

PMID- 19591509
TI  - Investigation of water and methanol sorption in monovalent- and multivalent-ion
      exchanged nafion membranes using electron spin resonance.
AB  - Electron spin resonance (ESR) spectroscopy was used to monitor the local
      environment of 2,2,6,6-tetramethyl-4-piperidone N-oxide (TEMPONE) spin probe in
      Li(+), Ca(2+), and Al(3+) ion-exchanged Nafion 117 membranes swollen with mixed
      methanol/water solvent at varying compositions. The (14)N hyperfine splitting,
      a(N), which reflects the local polarity of the nitroxide probe, remains nearly
      steady at higher solvent contents but increases substantially at lower solvent
      contents, reflecting close contact with the ions. The rotational rate (R) of the
      probe increased with solvent content, depending strongly on the amount of solvent
      at low contents but increasing more gradually at higher solvent contents, similar
      to the behavior of previously measured solvent translation diffusion
      coefficients. The rotational rate data from water-containing membranes were
      fitted using the Fujita free-volume diffusion model, which indicated that
      multivalent ions tend to increase the free volume fraction of the polymer while
      decreasing that of the solvent phase. Methanol-containing membranes exhibited
      greater variation with different exchange ions, but the data could not be fit
      using the free-volume model, suggesting that the assumption of two phases
      underlying the free-volume model might not apply to this case. The difference in
      the trends of swelling between water and methanol is consistent with previous
      results that have indicated different patterns of penetration for the two
      solvents. The results are interpreted in terms of changes in membrane morphology
      with higher-valence ions.

PMID- 19591507
TI  - Functional dynamics of the folded ankyrin repeats of I kappa B alpha revealed by
      nuclear magnetic resonance.
AB  - Inhibition of nuclear factor kappaB (NF-kappaB) is mainly accomplished by IkappaB
      alpha, which consists of a signal response sequence at the N-terminus, a six
      ankyrin repeat domain (ARD) that binds NF-kappaB, and a C-terminal PEST sequence.
      Previous studies with the ARD revealed that the fifth and sixth repeats are only
      partially folded in the absence of NF-kappaB. Here we report NMR studies of a
      truncated version of IkappaB alpha, containing only the first four ankyrin
      repeats, IkappaB alpha(67-206). This four-repeat segment is well-structured in
      the free state, enabling full resonance assignments to be made. H-D exchange,
      backbone dynamics, and residual dipolar coupling (RDC) experiments reveal regions
      of flexibility. In addition, regions consistent with the presence of micro- to
      millisecond motions occur periodically throughout the repeat structure.
      Comparison of the RDCs with the crystal structure gave only moderate agreement,
      but an ensemble of structures generated by accelerated molecular dynamics gave
      much better agreement with the measured RDCs. The regions showing flexibility
      correspond to those implicated in entropic compensation for the loss of
      flexibility in ankyrin repeats 5 and 6 upon binding to NF-kappaB. The regions
      showing micro- to millisecond motions in the free protein are the ends of the
      beta-hairpins that directly interact with NF-kappaB in the complex.

PMID- 19591510
TI  - QTAIM study of an alpha-helix hydrogen bond network.
AB  - The structures of 19 alpha-helical alanine-based peptides, 13 amino acids in
      length, have been fully optimized using density functional theory and analyzed by
      means of the quantum theory of atoms in molecules. Two types of N-H...O bonds and
      one type of C-H...O bond have been identified. The value of the electron density
      at hydrogen bond critical points corresponding to N-H...O interactions is higher
      than that of C-H...O interactions. The effect of amino acid substitution at the
      central position of the peptide on the hydrogen bond network of the alpha-helix
      has been assessed. The strength of the hydrogen bond network, measured as the
      summation of the electron density over the hydrogen bond critical points, may be
      used to explain experimental relative helix propensities of amino acids in cases
      where solvation and entropic effects cannot.

PMID- 19591511
TI  - Molecular dynamics simulations of ionic liquids: cation and anion dependence of
      self-diffusion coefficients of ions.
AB  - Molecular dynamics simulations of a series of ionic liquids [1-alkyl-3
      methylimidazolium (alkyl = methyl, ethyl, butyl, hexyl, and octyl), 1
      butylpyridinium, N-butyl-N,N,N-trimethylammonium and N-butyl-N
      methylpyrrolidinium cations combined with a (CF(3)SO(2))(2)N(-) anion
      ([mmim][TFSA], [emim][TFSA], [bmim][TFSA], [C(6)mim][TFSA], [C(8)mim][TFSA],
      [bpy][TFSA], [(n-C(4)H(9))(CH(3))(3)N][TFSA], and [bmpro][TFSA]) and a 1-butyl-3
      methylimidazolium combined with BF(4)(-), PF(6)(-), CF(3)CO(2)(-), CF(3)SO(3)(-),
      and (C(2)F(5)SO(2))(2)N(-) anions ([bmim][BF(4)], [bmim][PF(6)],
      [bmim][CF(3)CO(2)], [bmim][CF(3)SO(3)], and [bmim][BETA])] were carried out using
      the OPLS force field for ionic liquids. The force field was refined on the basis
      of ab initio molecular orbital calculations of isolated ions and experimental
      densities for four ionic liquids. The densities calculated for the 13 ionic
      liquids agreed with the experimental values within a 2% error. The self-diffusion
      coefficients calculated for the ions in the 13 ionic liquids were compared with
      the experimental values obtained by the NMR measurements. Although the calculated
      self-diffusion coefficients were about 1 order smaller than the experimental
      ones, the cation and anion dependence (the effects of alkyl chain length in
      imidazolium, cation structures, and anion species) of the experimental self
      diffusion coefficients was reproduced by the simulations quite well in most
      cases. The translational motion of the terminal carbon atoms in the alkyl chains
      of the imidazolium cations on the time scale of a few nanoseconds is
      significantly faster than that of the atoms in the imidazolium rings and anions,
      which suggests that the dynamics of atoms in the polar domains of the ionic
      liquids is significantly different from that in the nonpolar domains. The factors
      determining the self-diffusion coefficients of the ions are also discussed.

PMID- 19591513
TI  - Comparison of corticosteroid nasal sprays in relation to concomitant use and cost
      of other prescription medications to treat allergic rhinitis symptoms:
      retrospective cohort analysis of pharmacy claims data.
AB  - BACKGROUND AND OBJECTIVE: Intranasal corticosteroids are considered to be highly
      effective in patients with perennial or seasonal allergic rhinitis. Multiple
      intranasal corticosteroid products are available; however, an intranasal
      corticosteroid that treats nasal and ocular seasonal allergic rhinitis symptoms
      may be more cost effective by reducing the need for concomitant drugs. The
      purpose of this study was to compare the utilization and costs of concomitant
      allergic rhinitis drugs among commonly used branded intranasal corticosteroid
      drugs. METHODS: Pharmacy claims data between 1 April 2006 and 31 January 2008
      were obtained from the Wolters Kluwer SourceLx dataset. Patients with at least
      one pharmacy claim for a branded intranasal corticosteroid agent (fluticasone
      furoate, budesonide, mometasone or triamcinolone) during the index period of 1
      April 2007 through 31 July 2007 were included. Study outcomes assessed were time
      to concomitant use of prescription allergic rhinitis drugs (other than intranasal
      corticosteroids) and costs of those medications and intranasal corticosteroid
      drugs during a 60-day post-index period. RESULTS: A total of 793 349 patients
      were included in the study. At index, a majority of the patients were using
      mometasone (62.9%), followed by triamcinolone (21.1%), budesonide (15.1%) and
      fluticasone furoate (1.0%). After controlling for other covariates, patients
      receiving fluticasone furoate had on average a 21% lower risk of concomitant
      prescription allergic rhinitis drug use (adjusted hazard ratio [HR] 0.79; 95% CI
      0.75, 0.83) compared with the other three branded intranasal corticosteroid
      agents. Compared with fluticasone furoate, all other branded intranasal
      corticosteroid agents incurred statistically significant higher costs of
      concomitant allergic rhinitis drugs (6.3%, p = 0.002), resulting in increased
      costs to health plans of $US5-$US6 per patient over a 60-day period. Mean
      intranasal corticosteroid costs per patient during the 60-day follow-up period
      were lowest for budesonide ($US70.15), followed by fluticasone furoate
      ($US70.86), triamcinolone ($US73.23) and mometasone ($US75.48). CONCLUSION: In
      this cohort of intranasal corticosteroid users, fluticasone furoate was shown to
      reduce the need for concomitant prescription allergic rhinitis medications
      compared with other leading branded intranasal corticosteroid therapies,
      resulting in lower costs per patient and potentially leading to significant
      savings for health plans.

PMID- 19591512
TI  - Implications of the European Organisation for Research And Treatment Of Cancer
      (EORTC) guidelines on the use of granulocyte colony-stimulating factor (G-CSF)
      for lymphoma care.
AB  - Febrile neutropenia (FN) is a potentially life-threatening complication of
      myelosuppressive chemotherapy. The European Organisation for Research and
      Treatment of Cancer (EORTC) guidelines recommend use of primary granulocyte
      colony-stimulating factor (G-CSF) prophylaxis if the overall FN risk to a patient
      is >or=20%, or if a reduction in chemotherapy dose intensity correlates with a
      poorer outcome. Many of the regimens used for treatment of lymphoma, including R
      CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and
      prednisolone), are associated with an FN risk of approximately 20% or higher.
      Individual patient factors that may increase the risk of FN such as advanced age
      or advanced disease should be taken into account when assessing the need for G
      CSF support. Predictive models are being developed to facilitate individual risk
      assessment. Additional anti-infective prophylaxis may be indicated in some
      settings. There is now much evidence for the benefits of G-CSF in reducing the
      incidence of FN and facilitating delivery of chemotherapy, including dose
      escalated and dose-dense (interval-reduced) regimens. If given according to
      guidelines, G-CSF has the potential to reduce FN and related morbidity.
      Furthermore, by facilitating delivery of planned chemotherapy, use of G-CSF may
      potentially influence survival in the curative setting. Implementation of the
      EORTC guidelines will lead to a greater proportion of patients receiving G-CSFs,
      but the costs involved should be at least partly offset by a reduction in FN and
      its associated costs, including those of hospitalization.

PMID- 19591515
TI  - Effect of food on the pharmacokinetics of clozapine orally disintegrating tablet
      12.5 mg: a randomized, open-label, crossover study in healthy male subjects.
AB  - BACKGROUND AND OBJECTIVE: Food has reportedly not affected the systemic
      bioavailability of the atypical antipsychotic drug clozapine. However, searches
      of the medical literature could find no studies to support this food claim for
      any formulation of clozapine. The purpose of the current study was to assess the
      effect of food on the bioavailability and pharmacokinetics of clozapine orally
      disintegrating tablet (ODT) following single 12.5 mg doses in the healthy
      subjects in fasted and fed conditions. METHODS: This was a randomized, open
      label, two-way crossover study in which healthy males aged 18-45 years completed
      two dosing periods. In period I, subjects received one dose of clozapine ODT 12.5
      mg after an overnight fast and in period II they received one dose of clozapine
      ODT 12.5 mg within 30 minutes of consuming a high-fat/-calorie breakfast. Venous
      blood samples were taken at regular intervals before and after study drug
      administration, and plasma concentrations of clozapine and desmethylclozapine
      were measured from each blood sample. Standard pharmacokinetic parameters were
      calculated. Safety and tolerability were also assessed. RESULTS: Twenty-four
      subjects were enrolled: all the subjects completed the study and were included in
      the pharmacokinetic analyses. Pharmacokinetic results demonstrated significant
      differences in mean plasma concentration-time curves between fasted and fed
      conditions for both clozapine and desmethylclozapine at various time points after
      administration of a single clozapine ODT 12.5 mg dose. For both clozapine and
      desmethylclozapine, the lower limits of the 90% confidence intervals (CIs) for
      the geometric mean fed-to-fasted maximum plasma concentration (C(max)) ratios
      (0.73 for both clozapine and desmethylclozapine) were below the bioequivalence
      lower limit, 0.80. The mean C(max) of both clozapine and desmethylclozapine was
      decreased by approximately 20% when clozapine ODT was administered after a high
      fat/-calorie breakfast. However, the 90% CIs for the fed-to-fasted ratios of
      geometric means of area under the plasma concentration-time curve from time zero
      to the time of the last measurable concentration (AUC(last)) [1.01, 1.15 for
      clozapine; 1.00, 1.18 for desmethylclozapine) and from time zero to infinity
      (AUC(infinity)) [1.03, 1.14 for clozapine; 1.01, 1.15 for desmethylclozapine]
      were within the bioequivalence boundaries of 0.80-1.25. There were no serious
      adverse events, discontinuations due to adverse events, or abnormalities in
      clinical laboratory evaluations. Seventy-one adverse events were reported and 96%
      were mild in intensity - the most common adverse event was somnolence (42/71
      events). Two severe adverse events (syncope, n = 1 fasted subject; vasovagal
      syncope, n = 1 fed subject) were reported approximately 4 hours after
      administration of clozapine ODT and asystole (5-10 seconds) was associated with
      syncope in the fasted subject. CONCLUSIONS: When compared with drug
      administration in the fasted state, coadministration of food was shown to
      decrease the rate of clozapine absorption from clozapine ODT 12.5 mg as assessed
      by C(max) but had no effect on the extent of clozapine absorption as assessed by
      AUC(last) and AUC(infinity). The C(max) value for clozapine was approximately 20%
      lower in the fed versus the fasted state. Thus, clozapine ODT should be
      administered at least 1 hour before meals or after a light meal. The reported
      adverse events in 24 healthy male subjects were consistent with those expected
      from healthy subjects taking oral clozapine.

PMID- 19591514
TI  - Criterion validity of the ARthritis Treatment Satisfaction (ARTS) questionnaire:
      patient satisfaction with treatment and need for switching therapy.
AB  - BACKGROUND AND OBJECTIVE: The ARthritis Treatment Satisfaction (ARTS)
      questionnaire specifically assesses patients' satisfaction with osteoarthritis
      treatment. However, its usefulness is limited since its criterion validity is
      unknown. The goal of this research was to analyse the criterion validity of the
      questionnaire in order to identify a cut-off value able to differentiate patients
      who are satisfied and those who are unsatisfied with osteoarthritis treatment and
      to establish the possible need for switching therapy. METHODS: We used responses
      to the ARTS questionnaire from outpatients with osteoarthritis included in an
      open-label, non-controlled, naturalistic, prospective switching therapy study. In
      addition, patients' responses to two questions on satisfaction with treatment and
      osteoarthritis-related health status were recorded. Receiver operative
      characteristic (ROC) curve analyses with estimators of validity were determined.
      The correlation between responses to the ARTS questionnaire, the question
      regarding satisfaction with treatment, and the osteoarthritis-related health
      status assessment were also analysed. RESULTS: A total of 1756 male and female
      subjects were enrolled in the study. ROC curve analysis identified a cut-off
      point of >or=61 points as optimal for the criterion validity estimators of
      sensitivity (0.86), specificity (0.83), and positive (0.87) and negative (0.81)
      predictive values. This threshold value was used to identify patients satisfied
      with treatment and patients with a need to switch therapy (kappa coefficient of
      agreement 0.68 and 0.66, respectively). ARTS questionnaire scoring correlated
      with satisfaction with treatment (p < 0.0001), and with patient (r = 0.655, p <
      0.0001) and investigator (r = 0.565, p < 0.0001) health status assessments.
      CONCLUSION: The ARTS questionnaire was able to identify patients satisfied with
      treatment and those with a need to switch their osteoarthritis therapy.

PMID- 19591516
TI  - Effects of recombinant human granulocyte colony-stimulating factor (filgrastim)
      on ECG parameters in neutropenic patients: a single-centre, prospective study.
AB  - BACKGROUND AND OBJECTIVE: Human granulocyte colony-stimulating factor (G-CSF) is
      a haematopoietic hormone that promotes the growth, proliferation, differentiation
      and maturation of neutrophil precursors. Filgrastim is a recombinant human G-CSF.
      Myocardial infarction, atrial fibrillation and arrhythmia have been reported in
      several patients with malignancy receiving filgrastim, but a causal relationship
      with the drug has not been established. The purpose of this study was to
      investigate the changes in ECG parameters in neutropenic patients during
      treatment with filgrastim. METHODS: This was a single-centre, prospective study
      carried out in a hospital emergency room. Patients with neutropenia and
      malignancy who were required to receive filgrastim were eligible for the study.
      After a reference ECG had been obtained, filgrastim was administered to all
      patients at a dose of 5 microg/kg/day subcutaneously for 2 days. Follow-up ECGs
      were then obtained at 12-hourly intervals. Continuous telemetric monitoring was
      conducted throughout hospitalization. RESULTS: Serial ECG parameters were
      compared in 102 patients. There were no statistically significant differences
      between baseline and follow-up ECG measurements of rhythm, P-wave duration, PR
      interval, QRS-wave duration, corrected QT (QTc) interval, ECG axis, premature
      supraventricular events, ventricular arrhythmia, R-wave progression, right bundle
      branch block or left bundle branch block. There was a significant reduction in
      mean heart rate in subsequent ECGs compared with baseline (p < 0.05). CONCLUSION:
      This study did not demonstrate any ECG changes other than a significant reduction
      in mean heart rate in this selected population of neutropenic patients given 2
      days' treatment with subcutaneous 5 microg/kg/day of filgrastim.

PMID- 19591517
TI  - Efficiency of travoprost versus fixed-combination latanoprost/timolol.

PMID- 19591519
TI  - Chronic obstructive pulmonary disease in the elderly: an update on
      pharmacological management.
AB  - The prevalence of chronic obstructive pulmonary disease (COPD) continues to rise
      in association with an aging Western society. While barriers to receiving optimal
      healthcare exist for aging patients, pharmacotherapy of COPD in the elderly is
      important because the treatment benefits in this group are comparable to those
      seen in the younger COPD population. The frequent presence of co-morbidities and
      reduced clearance capacity make selection of pharmacotherapy in elderly patients
      with stable COPD challenging. The adverse effects of standard therapy for COPD
      may also be more pronounced in elderly patients. A careful risk-versus-benefit
      assessment should always be carried out when prescribing long-term inhaled
      bronchodilator and corticosteroid therapy to an elderly COPD patient, and when
      prescribing beta(2)-adrenoceptor agonists and methylxanthines, in particular, to
      those with cardiovascular co-morbidities. The present review focuses on the
      special considerations regarding initiation and maintenance of pharmacotherapy in
      elderly patients with stable COPD.

PMID- 19591520
TI  - Management of secondary hyperparathyroidism in the elderly patient with chronic
      kidney disease.
AB  - Patients with chronic kidney disease (CKD) are generally affected by secondary
      hyperparathyroidism (SHPT). High phosphate, low calcium and vitamin D deficiency
      represent the classical 'triad' involved into the pathogenesis of SHPT in renal
      insufficiency, in which downregulation of the parathyroid vitamin D receptor and
      calcium-sensing receptor represents a critical step. Recently, new studies
      indicate that fibroblast growth factor 23 may play a central role in the
      regulation of phosphate-vitamin D metabolism in patients with CKD. These new
      insights into the pathogenesis of SHPT will possibly improve the treatment of
      this condition in patients with CKD. The 'modern' treatment of SHPT in CKD
      patients consists of free-calcium and aluminium phosphate binders, vitamin D
      receptor activators and calcimimetics. However, calcium- and aluminium-based
      phosphate binders and calcitriol are therapeutic tools that are not without
      complications, including increasing the risk of cardiovascular calcification in
      patients with CKD. This review summarizes the current understanding and evidence
      supporting strategies for SHPT treatment in CKD patients, with particular focus
      on the elderly, although specific guidelines for control of this disorder in this
      age group are lacking.

PMID- 19591521
TI  - Constipation in the elderly: management strategies.
AB  - Constipation is a highly prevalent and bothersome disorder that negatively
      affects patients' social and professional lives and places a great economic
      burden on both patients and national health services. An accurate determination
      of the prevalence of constipation is difficult because of the various definitions
      used, but many epidemiological studies have shown that it affects up to 20% of
      the population at any one time. Although constipation is not a physiological
      consequence of normal aging, decreased mobility and other co-morbid medical
      conditions may contribute to its prevalence in older adults. Functional
      constipation is diagnosed when no secondary causes can be identified. Patients
      have some unusual beliefs about their bowel habits. Systematic attention to
      history, examination and investigation, especially in older people, can be highly
      effective in resolving problems and in enhancing quality of life. There is a
      considerable range of treatment modalities available for patients with
      constipation, but the clinical evidence supporting their use varies widely.
      However, if constipation is not managed proactively, patients can experience
      negative consequences, such as anorexia, nausea, bowel impaction or bowel
      perforation. The clinical benefits of various traditional pharmacological and non
      pharmacological agents remain unclear. The first steps in the treatment of simple
      constipation include increasing intake of dietary fibre and the use of a fibre
      supplement. Patients with severe constipation or those unable to comply with the
      recommended intake of fibre may benefit from the addition of laxatives. More
      recently, newer agents (e.g. tegaserod and lubiprostone), have been approved for
      the treatment of patients with chronic constipation. Additional work is needed to
      determine what role, if any, these agents may play in the treatment of patients
      with chronic constipation. The purpose of this review is to identify evidence
      based interventions for the prevention and management of constipation in the
      elderly.

PMID- 19591522
TI  - Hospitalizations because of adverse drug reactions in elderly patients admitted
      through the emergency department: a prospective survey.
AB  - BACKGROUND AND OBJECTIVES: Several studies have been conducted to determine the
      frequency and characteristics of adverse drug reactions (ADRs) in elderly
      populations, focusing on those leading to hospital admission. However, most of
      these studies have been limited in their ability to assess risk factors,
      particularly the renal status of patients. Thus, the aim of this prospective
      study was to assess the incidence of ADRs and associated factors leading to
      hospital admissions in the elderly population. METHODS: All patients aged > or
      =65 years admitted to the Toulouse University Hospital through the Emergency
      Department during four non-consecutive weeks in 2002-3 were included in this
      study except for patients in ambulatory care or admitted for intentional
      overdoses. The characteristics of patients admitted for a suspected ADR were
      compared with those of patients admitted for other reasons. RESULTS: The
      incidence of hospital admissions for ADRs was 8.37 per 100 admissions (95% CI
      6.52, 10.52), corresponding to 66 patients with ADRs among 789 admissions. The
      most important factors associated with ADRs were the number of drugs being taken
      (odds ratio [OR] 1.18; 95% CI 1.08, 1.29), self-medication (OR 2.34; 95% CI 1.18,
      4.66), use of antithrombotics (Anatomic Therapeutic and Chemical [ATC]
      classification B01; OR 2.26; 95% CI 1.33, 3.88) and use of antibacterial drugs
      (ATC J01; OR 4.04; 95% CI 1.50, 10.83). Surprisingly, exposure to drugs for acid
      related disorders was associated with a low risk of ADRs (OR 0.26; 95% CI 0.09,
      0.76). CONCLUSION: A significant incidence of ADRs leading to hospital admissions
      was found among elderly people. Our study showed that there is a need to increase
      the availability of information for the general public concerning potential ADRs
      due to self-medication and for prescribers concerning ADRs due to drug-drug
      interactions and polypharmacy.

PMID- 19591523
TI  - Use of antipsychotics among elderly nursing home residents with dementia in the
      US: an analysis of National Survey Data.
AB  - BACKGROUND: Atypical antipsychotic agents are increasingly being used for the
      treatment of behavioural and psychological symptoms of dementia. However, recent
      data suggest that the risk of adverse effects may offset the benefits of atypical
      agents in patients with dementia. OBJECTIVES: To examine utilization of
      antipsychotic medications and the factors associated with use of atypical
      antipsychotics among elderly nursing home residents with dementia. METHODS: The
      study involved the analysis of prescription and resident files of a nationally
      representative sample of residents from the 2004 National Nursing Home Survey
      (NNHS). The study sample included an unweighted sample of 6103 elderly nursing
      home residents aged > or =65 years with dementia. The analysis focused on the use
      of six atypical antipsychotic agents and 11 typical agents. Descriptive weighted
      analysis was performed to examine the antipsychotic prevalence patterns in
      elderly nursing home residents with dementia. Multiple logistic regression
      analysis within the conceptual framework of Andersen's Behavioural Model was used
      to examine the predisposing, enabling and need characteristics associated with
      use of atypical antipsychotics. RESULTS: According to the 2004 NNHS, the overall
      prevalence of dementia among elderly nursing home residents was 52.58%. Most of
      the elderly with dementia were female (77%), aged > or =85 years (56%), non
      Hispanic (97%) and White (88%). Antipsychotic medications were taken by 32.88% of
      elderly patients with dementia. More elderly residents received atypical agents
      (31.63%) than typical agents (1.75%). Among the predisposing characteristics, the
      odds of receiving atypical antipsychotics were lower for females than males. The
      enabling factor facility bed capacity was significantly associated with use of
      atypical antipsychotics. Among the need characteristics, the likelihood of
      receiving atypical antipsychotic agents increased with dependence in decision
      making ability, indicators of depressed mood and behavioural symptoms. The
      likelihood of receiving atypical antipsychotic agents decreased with increasing
      dependence for out-of-bed mobility and increased total activities of daily
      living. The odds of receiving atypical antipsychotic treatment increased with the
      diagnosis of schizophrenia, bipolar mania and anxiety among dementia patients.
      CONCLUSION: Nearly one-third of elderly nursing home residents with dementia
      received antipsychotic medications, mainly atypical agents. Predisposing,
      enabling and need factors influenced the use of atypical agents in dementia
      patients. These findings suggest a need to optimize use of atypical
      antipsychotics in elderly dementia patients in nursing homes in the light of
      recent efficacy and safety data.

PMID- 19591524
TI  - Patterns of drug use and factors associated with polypharmacy and excessive
      polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross
      sectional analysis.
AB  - BACKGROUND: Although the increasing use of drugs in elderly persons has raised
      many concerns in recent years, the process leading to polypharmacy (PP) and
      excessive polypharmacy (EPP) remains largely unknown. OBJECTIVE: To describe the
      number and type of drugs used and to evaluate the role of different factors
      associated with PP (i.e. 6-9 drugs) and EPP (i.e. > or =10 drugs), with special
      reference to the number and type of medical diagnoses and symptoms, in a
      population of home-dwelling elderly persons aged > or =75 years. METHODS: The
      study was a cross-sectional analysis of a population-based cohort in 1998. The
      population consisted of home-dwelling elderly persons aged > or =75 years in the
      city of Kuopio, Finland. The data for the analysis were obtained from the Kuopio
      75+ Study, which drew a random sample of 700 elderly residents aged > or =75
      years living in the city of Kuopio from the population register. Of these, 601
      attended a structured clinical examination and an interview carried out by a
      geriatrician and a trained nurse in 1998. For this analysis, all home-dwelling
      elderly participants (n = 523) were included. Study data were expressed as
      proportions and means with standard deviations. The factors associated with PP
      and EPP were examined by multinomial logistic regression. RESULTS: The most
      commonly used drugs were cardiovascular drugs (97% in EPP, 94% in PP and 59% in
      non-PP group) and analgesics (89%, 76% and 54%), respectively. Use of
      psychotropics was markedly higher in the EPP group (77%) than in the PP (42%) and
      non-PP groups (20%). The mean number of drugs per diagnosis was 3.6 in the EPP
      group, 2.6 in the PP group and 1.6 in the non-PP group. Factors associated only
      with EPP were moderate self-reported health (odds ratio [OR] 2.05; 95% CI 1.08,
      3.89), female gender (OR 2.43; 95% CI 1.27, 4.65) and age > or =85 years (OR
      2.84; 95% CI 1.41, 5.72). Factors that were associated with both PP and EPP
      included poor self-reported health (PP: OR 2.15; 95% CI 1.01, 4.59 and EPP: OR
      6.02; 95% CI 2.55, 14.20), diabetes mellitus (PP: OR 2.28; 95% CI 1.26, 4.15 and
      EPP: OR 2.07; 95% CI 1.03, 4.18), depression (PP: OR 2.13; 95% CI 1.16, 3.90 and
      EPP: OR 2.93; 95% CI 1.51, 5.66), pain (PP: OR 2.69; 95% CI 1.68, 4.30 and EPP:
      OR 2.74; 95% CI 1.56, 4.82), heart disease (PP: OR 2.51; 95% CI 1.54, 4.08 and
      EPP: OR 4.63; 95% CI 2.45, 8.74) and obstructive pulmonary disease (including
      asthma or chronic obstructive pulmonary disease) [PP: OR 2.79; 95% CI 1.24, 6.25
      and EPP: OR 6.82; 95% CI 2.87, 16.20]. CONCLUSION: The study indicates that the
      factors associated with PP and EPP are not uniform. Age > or =85 years, female
      gender and moderate self-reported health were factors associated only with EPP,
      while poor self-reported health and several specific disease states were
      associated with both PP and EPP. The high number of drugs per diagnosis observed
      in this study calls for a thorough assessment of the need for and outcomes
      associated with use of these drugs.

PMID- 19591527
TI  - Outliers and patients with adverse drug reactions.

PMID- 19591526
TI  - Medication problems in older, newly diagnosed cancer patients in Canada: How
      common are they? A prospective pilot study.
AB  - BACKGROUND: Prescribing for older patients is challenging and complex. Cancer
      patients are at a considerable increased risk of drug-related problems because
      they typically receive a large number of medications during their cancer
      treatment, both for the cancer itself and for supportive care. Few studies have
      examined the scope of this problem in older newly diagnosed cancer patients.
      OBJECTIVE: To investigate the number and severity of potential drug problems and
      factors associated with the occurrence of potential drug problems in older newly
      diagnosed cancer patients. METHODS: This prospective pilot study was conducted in
      newly diagnosed cancer patients aged > or =65 years recruited in the Segal Cancer
      Centre, Jewish General Hospital, Montreal, Quebec, Canada. Vigilance Sante
      software was used to identify the presence and type of potential drug problems.
      Logistic regression analyses were used to identify factors associated with the
      presence of one or more severe or moderately severe potential drug problems.
      RESULTS: There were 112 participants with a mean age of 74.2 years, and 70% were
      women. A total of 103 patients (92%) were taking medications. The median number
      of medications per patient was 5 (interquartile range 3-9) and a total of 247
      potential drug problems were identified. Sixty-four patients (62.1%) had a
      potential drug problem of any level of severity and 49 patients had a potential
      moderate/severe drug problem identified (47.6%). Two (0.8%) potential drug
      problems of the most severe level were identified, 122 warnings (49.4%) of all
      potential problems were of moderate severity and 123 warnings (49.8%) were at the
      least severe level. Factors associated with having one or more moderate/severe
      potential drug problems were taking five or more drugs and age > or =76 years.
      CONCLUSION: The majority of older newly diagnosed cancer patients in this study
      were taking at least one medication and the median number of medications per
      patient was 5. Published studies have shown that medication problems are common
      in community-dwelling older persons, but they are mostly of low severity. In this
      group of older newly diagnosed cancer patients, potential medication problems
      were also found to be common; however, half of the potential problems identified
      were of moderate severity.

PMID- 19591525
TI  - "I just take what I am given": adherence and resident involvement in decision
      making on medicines in nursing homes for older people: a qualitative survey.
AB  - BACKGROUND: Adherence to medication is generally considered to be poor in many
      patient groups, but little is known about adherence to medication in the nursing
      home setting. It is also unclear if residents in nursing homes are involved in
      decision making about medication. OBJECTIVE: This study sought to explore
      adherence to medication and resident involvement in prescribing and decision
      making in regard to medicines in the nursing home setting. METHODS: This was a
      qualitative study. Participants took part in either semi-structured interviews
      (general practitioners [GPs] and residents) or focus groups (nurses) to discuss
      issues around prescribing and adherence to medication in nursing homes for older
      people in Northern Ireland. All interviews and focus groups were digitally
      recorded, fully transcribed and analysed using the principles of constant
      comparison. RESULTS: Eight GPs and 17 residents participated in semi-structured
      interviews and nine nurses participated in two focus groups (n = 4; n = 5). The
      main theme that emerged was control, which was manifested in many ways. Both
      groups of healthcare professionals needed to maintain control of prescribing or
      administration of medication in order to ensure safety, quality and continuity of
      care. All residents accepted control without question, reported that they were
      adherent to medication and had little involvement in prescribing decisions or
      administration of their own medicines. Although the healthcare professionals
      thought that more involvement in decisions around medication would contribute to
      resident autonomy and empowerment, it was also recognized that this could
      adversely affect control within the nursing home. CONCLUSION: Although adherence
      with medication was generally perceived not to be a problem in the nursing homes
      setting in this study, other findings raise major challenges for resident
      involvement in an important aspect of their own care. Although there may be some
      residents, because of cognitive decline, who are unable to become involved in
      aspects of decisions about prescribing and self-administration, healthcare
      professionals providing care to these patients should strive to involve them as
      far as possible in their own care.

PMID- 19591528
TI  - Do nanomedicines require novel safety assessments to ensure their safety for long
      term human use?
AB  - Nanomaterials have different chemical, physical and biological characteristics
      than larger materials of the same chemical composition. These differences give
      nanotechnology a double identity: their use implies novel and interesting medical
      and/or industrial applications but also potential danger for human and
      environmental health. Here, we briefly review the most important types of
      nanomaterials, the difficulties in assessing safety or toxicity, and describe
      existing test protocols used in nanomaterial safety evaluation. In general, the
      big challenge of nanotechnology, particularly for nanomedicine (nano
      bioengineering), is to understand which nano-specific characteristics interact
      with particular biological systems and functions in order to optimize the
      therapeutic potential and reduce the undesired responses. The evaluation of the
      safety of medicinal nanomaterials, especially for long-term application, is an
      important challenge for the near future. At present, it is still too early to
      predict, on the basis of the characteristics of the nanomaterial, a possible
      biological response because no reliable database exists. Therefore, a case-by
      case approach for hazard identification is still required, so it is difficult to
      establish a risk assessment framework.

PMID- 19591529
TI  - Serenoa repens (saw palmetto): a systematic review of adverse events.
AB  - Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most
      widely used herbal preparations for the treatment of lower urinary tract symptoms
      (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized
      controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for
      the treatment of LUTS and BPH have been published, no systematic review on its
      drug interactions or adverse events currently exists. This review assesses all
      available human safety data of S. repens monopreparations. Systematic literature
      searches were conducted from date of inception to February 2008 in five
      electronic databases; reference lists and our departmental files were checked for
      further relevant publications. Information was requested from spontaneous
      reporting schemes of the WHO and national safety bodies. Twenty-four
      manufacturers/distributors of S. repens preparations and four herbalist
      organizations were contacted for additional information. No language restrictions
      were imposed. Only reports of adverse events in humans from monopreparations of
      S. repens were included. Data from all articles, regardless of study design,
      reporting adverse events or interactions were independently extracted by the
      first author and validated by the second. Forty articles (26 randomized
      controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and
      4 case reports/series) were included. They suggest that adverse events associated
      with the use of S. repens are mild and similar to those with placebo. The most
      frequently reported adverse events are abdominal pain, diarrhoea, nausea,
      fatigue, headache, decreased libido and rhinitis. More serious adverse events
      such as death and cerebral haemorrhage are reported in isolated case reports and
      data from spontaneous reporting schemes, but causality is questionable. No drug
      interactions were reported. Currently available data suggest that S. repens is
      well tolerated by most users and is not associated with serious adverse events.
      The majority of adverse events are mild, infrequent and reversible, and include
      abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and
      rhinitis. We found no evidence for drug interactions with S. repens. However,
      higher quality reporting of adverse events is essential if safety assessments are
      to be improved in future.

PMID- 19591530
TI  - Amyotrophic lateral sclerosis-like conditions in possible association with
      cholesterol-lowering drugs: an analysis of patient reports to the University of
      California, San Diego (UCSD) Statin Effects Study.
AB  - BACKGROUND: While cases of amyotrophic lateral sclerosis (ALS) or ALS-like
      conditions have arisen in apparent association with HMG-CoA reductase inhibitors
      ('statins') and/or other lipid-lowering drugs (collectively termed 'statins' in
      this paper for brevity), additional information is needed to understand whether
      the connection may be causal. The University of California, San Diego (UCSD)
      Statin Effects Study is a patient-targeted adverse event surveillance project
      focused on lipid-lowering agents, whose aim is to capitalize on patient reporting
      to further define characteristics and natural history of statin adverse effects
      (AEs), and to ascertain whether a patient-targeted surveillance system might lead
      to presumptive identification of previously unrecognized AEs. ALS was a candidate
      'new' AE identified through this process. The aim of the analysis presented here
      was to examine characteristics and natural history of reported statin-associated
      ALS-like conditions with attention to factors that may bear on the issue of
      causality. METHODS: For the present analysis, we focused on cases of statin
      associated ALS that were reported to our study group prior to publication of a
      possible statin-ALS association. Of 35 identified subjects who had contacted the
      UCSD Statin Effects Study group to report ALS or an ALS-like condition, 18 could
      not be reached (e.g. contact information was no longer valid). Six were unable to
      participate (e.g. due to progression of their disease). Of the 11 who could be
      contacted and were able to participate, one declined to give informed consent.
      The remaining ten, with either a formal or probable diagnosis of ALS in the
      context of progressive muscle wasting/weakness arising in association with lipid
      lowering drug therapy, completed a mail or phone survey eliciting information
      about ALS symptom onset and change in association with drug use/modification and
      development of statin-associated AEs. We reviewed findings in the context of
      literature on statin antioxidant/pro-oxidant balance, as well as ALS mechanisms
      involving oxidative stress and mitochondrial dysfunction. RESULTS: All ten
      subjects reported amelioration of symptoms with drug discontinuation and/or onset
      or exacerbation of symptoms with drug change, rechallenge or dose increase. Three
      subjects initiated coenzyme Q10 supplementation; all reported initial benefit.
      All subjects reportedly developed statin AEs (not indicative of ALS) prior to ALS
      symptom onset, strongly disproportionate to expectation (p < 0.001). Since this
      reflects induction of pro-oxidant effects from statins, these findings lend
      weight to a literature-supported mechanism by which induction by statins of
      oxidative stress with amplification of mitochondrial dysfunction, arising in a
      vulnerable subgroup, may propel mechanisms underlying both AEs and, more rarely,
      ALS. CONCLUSION: A theoretical foundation and preliminary clinical observations
      suggest that statins (and other lipid-lowering drugs) may rarely be associated
      with ALS in vulnerable individuals in whom pro-oxidant effects of statins
      predominate. Our observations have explanatory relevance extending to ALS causes
      that are not statin associated and to statin-associated neurodegenerative
      conditions that are not ALS. They suggest means for identification of a possible
      vulnerable subgroup. Indeed whether statins may, in contrast, confer ALS
      protection when antioxidant effects predominate merits examination.

PMID- 19591531
TI  - Application of the Bow-Tie model in medication safety risk analysis: consecutive
      experience in two hospitals in the Netherlands.
AB  - BACKGROUND: To improve medication safety effectively, one should systematically
      analyse and assess the risks for medication errors and determine the possible
      causes. So far, no risk-analysis instrument exists in healthcare that can be used
      to analyse and visualize risks, causes and consequences of potential adverse
      events in a prospective manner. In high-risk industries such as petrochemistry
      and aviation, the Bow-Tie model is frequently used. This model combines causes,
      errors, preventive and recovery measures, and consequences in one model and gives
      insight into the magnitude and causes of existing safety risks. The aim of our
      project was to study the usefulness of the Bow-Tie model in the hospital setting
      for prospective analysis of risks in the medication process in order to develop a
      practicable method. METHODS: The model was first adapted to the clinical setting.
      Thereafter, the risk-analysis model was applied in a large tertiary teaching
      hospital in multidisciplinary sessions. The sessions and risk-analysis method
      were evaluated on the following aspects: applicability, comprehensibility,
      creation of awareness in and motivation of participants, and the capability of
      the 'system approach' (the approach taken by the Bow-Tie model, which focuses on
      the conditions under which individuals work and tries to build defences to avert
      errors or mitigate their effects, in contrast to a 'person approach', which
      focuses on errors of individuals, blaming them for forgetfulness, inattention
      etc.). Based on this evaluation, the risk analysis method was adjusted and
      consecutively applied in a general teaching hospital. After evaluation of the
      sessions in the second hospital a recommended method for risk analysis with the
      Bow-Tie model was defined. RESULTS: The risk-analysis method with the Bow-Tie
      model in the first hospital gave insight into many medication safety-related
      risks. However, the method was insufficient on comprehensibility and on the
      creation of awareness and motivation owing to a great number of determined risks
      which made thorough analysis, drawing of Bow-Ties and prioritizing difficult. The
      adjusted method in the second hospital focused more on the in-depth analysis of a
      small number of important safety issues of a department with specific attention
      for underlying causes. This approach was considered better in applicability,
      comprehensibility and the creation of awareness. Furthermore, by analyzing
      underlying causes, more attention could be paid to latent conditions (which can
      translate into error-provoking conditions) within the system. CONCLUSION: We
      found the Bow-Tie to be an appropriate model for prospective risk analysis of
      medication safety in a hospital. By applying the model in two hospitals
      consecutively we developed a feasible method for risk-analysis sessions. Key
      factors of this recommended method are a focus on the prioritized selection of
      safety issues and specific attention to latent conditions within the system by
      analysing these safety issues in depth to the root causes with the help of the
      Bow-Tie model.

PMID- 19591532
TI  - Thiazolidinediones and cardiovascular events in patients with type 2 diabetes
      mellitus: a retrospective cohort study of over 473,000 patients using the
      National Health Insurance database in Taiwan.
AB  - BACKGROUND AND OBJECTIVE: Concern has been expressed over the cardiovascular
      risks associated with rosiglitazone and pioglitazone. This study investigates the
      association between oral antihyperglycaemics (rosiglitazone, pioglitazone,
      sulfonylureas and metformin) with myocardial infarction, congestive heart
      failure, angina pectoris, stroke and transient ischaemic attack. METHODS: We used
      Taiwan's 2000-5 National Health Insurance database to conduct a population-based,
      retrospective cohort study of 473 483 newly diagnosed patients with type 2
      diabetes mellitus. We classified study patients into five basic groups based on
      the agents they were prescribed during the study period: (i) rosiglitazone
      monotherapy; (ii) pioglitazone monotherapy; (iii) sulfonylurea-based therapy;
      (iv) metformin-based therapy; and (v) sulfonylurea and metformin-based therapy.
      Cox proportional hazards models were used to evaluate the association between the
      use of rosiglitazone or pioglitazone and the occurrence of cardiovascular events.
      RESULTS: Patients receiving rosiglitazone monotherapy were at higher risk for any
      cardiovascular event (hazard ratio [HR] 1.89; 95% CI 1.57, 2.28), myocardial
      infarction (HR 2.09; 95% CI 1.36, 3.24), angina pectoris (HR 1.79; 95% CI 1.39,
      2.30) and transient ischaemic attack (HR 2.57; 95% CI 1.33, 4.96) than those
      receiving metformin monotherapy. Overall, add-on rosiglitazone and pioglitazone
      were associated with comparable cardiovascular risk. Based on our point
      estimates, pioglitazone as an add-on therapy was found to have a favourable, but
      nonsignificant, effect on outcome. CONCLUSIONS: Our findings extend the evidence
      from current literature to a real-world setting and support data from clinical
      trials that the disadvantages or harm caused by thiazolidinediones, especially
      rosiglitazone, may outweigh their benefits in patients with type 2 diabetes.

PMID- 19591534
TI  - Comment on "Drug-induced thrombocytopenia: an updated systematic review".

PMID- 19591536
TI  - Toward the understanding of the photodynamic activity of m-THPP encapsulated in
      PLGA nanoparticles: correlation between nanoparticle properties and in vivo
      activity.
AB  - Biodegradable polymeric nanoparticles (NP) are promising delivery systems for
      photosensitizers (PS). A hydrophobic PS, the meso-tetra(p-hydroxyphenyl)porphyrin
      (m-THPP) was encapsulated into NP made of poly(D,L-lactide-co-glycolide) using an
      emulsification-diffusion method, and poly(vinyl alcohol) (PVAL) as stabilizing
      agent during the emulsification step. Three batches of NP with mean diameters of
      117, 285, and 593 nm, respectively, were prepared. NP of 117 nm exhibited the
      highest rate of reactive oxygen species production and the fastest m-THPP release
      determined by the transfer of m-THPP to serum proteins in vitro. Similarly, the
      117 nm batch exhibited the highest in vivo photodynamic activity, as established
      in the chick embryo chorioallantoic membrane model. Our data suggest that m-THPP
      release before illumination is an important step for in vivo photodynamic
      activity especially for large NP. The NP size and the amount of residual PVAL at
      the NP surface were shown to control both the PS release and activity.

PMID- 19591533
TI  - Remedies containing Asteraceae extracts: a prospective observational study of
      prescribing patterns and adverse drug reactions in German primary care.
AB  - BACKGROUND: The use of complementary therapies by patients has increased over the
      past 20 years, both in terms of self-medication and physician prescriptions.
      Among herbal medicines, those containing extracts of Asteraceae (Compositae),
      such as Echinacea spp., Arnica montana, Matricaria recutita and Calendula
      officinalis, are especially popular in the primary-care setting. However, there
      remains a gap between the growing acceptance of these remedies and the lack of
      data on their safety. OBJECTIVE: The aim of this study was to analyse prescribing
      patterns and adverse drug reactions (ADRs) for Asteraceae-containing remedies in
      Germany. METHODS: Primary-care physicians, all of whom were members of the German
      National Association of Anthroposophic Physicians were invited to participate in
      this prospective, multicentre, observational study. During the study period
      (September 2004 to September 2006), all prescriptions and suspected ADRs for both
      conventional and complementary therapies were documented using a web-based
      system. The study centre monitored all ADR reports and conducted a causality
      assessment according to Uppsala Monitoring Centre guidelines. Relative risks
      (RRs) and proportional reporting ratios (PRRs) were calculated. RESULTS: Thirty
      eight physicians, 55% of whom were general practitioners and 45% were
      specialists, fulfilled the technical requirements and were included in the
      investigation. Because documenting all ADRs (i.e. serious and nonserious) was
      time consuming, only a subgroup consisting of seven physicians agreed to report
      nonserious in addition to serious ADRs. During the study period, a total of 50
      115 patients were evaluated and 344 ADRs for conventional and complementary
      remedies were reported. Altogether, 18 830 patients (58.0% female, 60.3%
      children) received 42 378 Asteraceae-containing remedies. The most frequently
      prescribed Asteraceae was Matricaria recutita (23%), followed by Calendula
      officinalis (20%) and Arnica montana (20%). No serious ADRs for Asteraceae
      containing remedies were reported. In the analysis of the subgroup of seven
      physicians who also documented nonserious ADRs, 11 nonserious ADRs for Asteraceae
      containing remedies occurred in 6961 patients, resulting in an RR of 0.13 (95% CI
      0.07, 0.23). The majority of reported ADRs for Asteraceae-containing remedies
      were classified as uncommon. A subgroup analysis comparing phytotherapeutic and
      homoeopathic preparations did not reveal any relevant differences. The PRR for
      Asteraceae-containing remedies with respect to all other prescriptions was 1.7
      (95% CI 1.0, 2.0) for the system organ class 'skin and subcutaneous tissue
      disorders' (six ADRs) and 1.0 (95% CI 0.3, 3.6) for 'gastrointestinal disorders'
      (three ADRs). Neither result was significant according to the PRR criteria
      developed by Evans et al. CONCLUSION: This is the first study to provide a
      systematic overview of prescribing patterns and ADRs for Asteraceae-containing
      remedies in the German primary-care sector. Asteraceae-containing remedies were
      used frequently in this context, especially among children. Our results indicate
      that treatment with Asteraceae-containing remedies is not associated with a high
      risk of ADRs.

PMID- 19591537
TI  - Uptake of plasmid-loaded nanoparticles in breast cancer cells and effect on Plk1
      expression.
AB  - The development of nucleic acid-based drugs for cancer therapeutic application
      has shown promising results in the past. However the delivery of these drugs to
      target cells is one problem which remains to be resolved. Nanoparticles have been
      described as promising strategies to deliver drugs into target cells. Human serum
      albumin (HSA) nanoparticles conjugated to trastuzumab for a cell type-specific
      targeting of human epidermal growth factor receptor 2 (HER2)-overexpressing cells
      were developed with incorporated expression plasmids for small hairpin RNAs
      (shRNAs) targeting polo-like kinase 1 (Plk1). Plk1 is a promising target for such
      an approach because it is overexpressed in all known cancer types and is a
      negative prognostic factor. Receptor-mediated uptake of the trastuzumab-modified
      nanoparticles into HER2-positive cells could be observed leading to reduced Plk1
      expression. Taken together, HSA nanoparticles represent promising tools to
      deliver expression plasmids for shRNAs into target cells and should be further
      evaluated with regard to a therapeutic application of RNA interference in cancer
      therapy.

PMID- 19591538
TI  - Particles emitted from indoor combustion sources: size distribution measurement
      and chemical analysis.
AB  - This study is primarily focused toward measuring the particle size distribution
      and chemical analysis of particulate matter that originates from combustion
      sources typically found in Indian urban homes. Four such sources were selected:
      cigarette, incense stick, mosquito coil, and dhoop, the latter being actually a
      thick form of incense stick. Altogether, seven of the most popular brands
      available in the Indian market were tested. Particle size distribution in the
      smoke was measured using a scanning mobility particle sizer, using both long and
      nano forms of differential mobility analyzer (DMA), with readings averaged from
      four to six runs. The measurable particle size range of the nano DMA was 4.6 nm
      to 157.8 nm, whereas that of the long DMA was 15.7 nm to 637.8 nm. Therefore,
      readings obtained from the long and the nano DMA were compared for different
      brands as well as for different sources. An overlap was seen in the readings in
      the common range of measurement. The lowest value of peak concentration was seen
      for one brand of incense stick (0.9 x 10(6) cm(-3)), whereas the highest (7.1 x
      10(6) cm(-3)) was seen for the dhoop. Generally, these sources showed a peak
      between 140 and 170 nm; however, 2 incense stick brands showed peaks at 79 nm and
      89 nm. The dhoop showed results much different from the rest of the sources, with
      a mode at around 240 nm. Chemical analysis in terms of three heavy metals
      (cadmium, zinc, and lead) was performed using graphite tube atomizer and flame
      atomic absorption spectrophotometer. Calculations were made to assess the
      expected cancer and noncancer risks, using published toxicity potentials for
      these three heavy metals. Our calculations revealed that all the sources showed
      lead concentrations much below the American Conference of Governmental Industrial
      Hygienists (ACGIH) threshold limit value (TLV) level. One of the two mosquito
      coil brands (M(2)) showed cadmium concentrations two times higher than the
      California Environmental Protection Agency (Cal EPA) reference exposure level
      (REL). The latter also showed the highest carcinogenic risks of 350 people per
      million population. The amount of zinc obtained from the sources, however, was
      found to be quite below the standard limits, implying no risk in terms of zinc.

PMID- 19591544
TI  - Insulin glargine and cancer--an unsubstantiated allegation.

PMID- 19591545
TI  - Massachusetts health insurance mandate: effects on neurosurgical practice.
AB  - OBJECT: Massachusetts' health insurance mandate and subsidized insurance program,
      Commonwealth Care, have been active for 2 years. METHODS: The financial impact on
      the neurosurgery division and demographics of the relevant patient groups were
      assessed. The billing records of neurosurgical patients from January 2007 to
      September 2008 were collected and analyzed. RESULTS: Commonwealth Care comprised
      2.2% of neurosurgical inpatients, and these patients did not have significantly
      different acuity or lengths of stay from the average. Length of stay of
      MassHealth patients was significantly greater, although acuity was significantly
      lower than the average. Increased free care reimbursement and increased
      MassHealth/Commonwealth Care enrollment resulted in a net gain in reimbursement
      of hospital charges. CONCLUSIONS: The increased insurance rates have resulted in
      increased reimbursement for the neurosurgical division.

PMID- 19591546
TI  - Transfrontoethmoidal approach to medial intraconal lesions.
AB  - Object The standard superior craniotomy approach through the orbital roof is
      obstructed by numerous muscles, nerves, and vessels. Accessing the medial
      intraconal space also involves considerable brain retraction. The authors present
      a modified approach through the frontal sinus that overcomes these limitations.
      Methods Seven fixed silicone-injected cadaveric specimens were dissected
      bilaterally. In addition to the superior orbital wall, the ethmoidal sinuses and
      medial orbital wall were removed. The anatomical relationships between the major
      neurovascular complexes in the medial intraconal space and the optic nerve were
      observed. Results Intraconally, working space was created both in a "superior
      window" between the superior oblique and levator palpebrae muscle and in a
      "medial window" between the superior oblique and medial rectus muscle. The
      superior window mainly created an ipsilateral trajectory to the deep target. The
      medial window, which created a contralateral trajectory, provided a more inferior
      view of the medial intraconal space. Removal of the medial orbital wall further
      widened the exposure obtained from the superior window. The combination of these
      working windows makes the medial surface of the optic nerve available for
      exploration from multiple angles. Most of the major neurovascular complexes of
      the posterior orbit can be retracted safely without impinging on the optic nerve.
      Conclusions This novel extradural transfrontoethmoidal approach affords a direct
      view to the medial posterior orbit without major conflicts with intraconal
      neurovascular structures and requires minimal brain manipulation. The approach
      appears to offer advantages for medially located intraconal lesions.

PMID- 19591547
TI  - Spontaneous intracranial hypotension syndrome: a novel speculative
      physiopathological hypothesis and a novel patch method in a series of 28
      consecutive patients.
AB  - OBJECT: Spontaneous intracranial hypotension (SIH) is a potentially serious
      pathological syndrome consisting of specific symptoms and neuroradiological signs
      that can sometimes be used to assess the efficacy of the treatment. In this paper
      the authors report a series of 28 patients with this syndrome who were all
      treated with an epidural blood patch at the authors' institution. The authors
      propose a novel physiopathological theory of SIH based on some anatomical
      considerations about the spinal venous drainage system. METHODS: Between January
      1993 and January 2007, the authors treated 28 patients in whom SIH had been
      diagnosed. Twenty-seven of the 28 patients presented with the typical findings of
      SIH on brain MR imaging (dural enhancement and thickening subdural collections,
      caudal displacement of cerebellar tonsils, and reduction in height of
      suprachiasmatic cisterns). The sites of the patients' neuroradiologically
      suspected CSF leakage were different, but the blood patch procedure was performed
      at the lumbar level in all patients. The patients were then assessed at 3-month
      and 1- and 3-year follow-up visits. At the last visit (although only available
      for 11 patients) 83.3% of patients were completely free from clinical symptoms
      and 8.3% complained of sporadic orthostatic headache. RESULTS: The authors think
      that in the so-called SIH syndrome, the dural leak, even in those cases in which
      it can be clearly identified on neuroradiological examinations, is not the cause
      of the disease but the effect of the epidural hypotension maintained by the
      inferior cava vein outflow to the heart. The goal of their blood patch procedure
      (a sort of epidural block obtained using autologous blood and fibrin glue at the
      L1-2 level) is not to seal CSF leaks, but instead to help in reversing the CSF
      blood gradient within the epidural space along the entire cord. CONCLUSIONS: The
      authors' procedure seems to lead to good and long-lasting clinical results.

PMID- 19591548
TI  - Onyx embolization of carotid-cavernous fistulas.
AB  - OBJECT: The authors conducted a study to determine the safety and efficacy of
      embolization of carotid-cavernous fistulas (CCFs) with the ethylene vinyl alcohol
      copolymer, Onyx. METHODS: They prospectively collected data in all patients with
      CCFs who underwent Onyx-based embolization at their institution over a 3-year
      period. The type of fistula, route of embolization, viscosity of Onyx, additional
      use of coils, extent of embolization, procedural complications, and clinical
      follow-up were recorded. RESULTS: A total of 12 patients (5 men and 7 women who
      were age 24-88 years) underwent embolization in which Onyx was used. There were 1
      Barrow Type A, 1 Type B, 3 Type C, and 7 Type D fistulas. Embolization was
      performed via a transvenous route in 8 cases and a transarterial route in 4
      cases. Onyx 34 was used in all but 2 cases: a direct Type A fistula embolized
      with Onyx 500 and an indirect Type C fistula embolized with Onyx 18. Adjuvant
      embolization with framing coils was performed in 7 cases. All procedures were
      completed in a single session. Immediate fistula obliteration was achieved in all
      cases. Clinical resolution of presenting symptoms occurred in 100% of the
      patients by 2 months. Neurological complications occurred in 3 patients. One
      patient developed a complete cranial nerve (CN) VII palsy that has not resolved.
      Two patients developed transient neuropathies--1 a Horner syndrome and partial CN
      VI palsy, and 1 a complete CN III and partial CN V palsy. Radiographic follow-up
      (mean 16 months, range 4-35 months) was available in 6 patients with complete
      resolution of the lesion in all. CONCLUSIONS: Onyx is a liquid embolic agent that
      is effective in the treatment of CCFs but not without hazards. Postembolization
      cavernous sinus thrombosis and swelling may result in transient compressive
      cranial neuropathies. The inherent gradual polymerization properties of Onyx
      allow for casting of the cavernous sinus but may potentially result in deep
      penetration within arterial collaterals that can cause CN ischemia/infarction.
      Although not proven, the angiotoxic effects of dimethyl sulfoxide may also play a
      role in postembolization CN deficits.

PMID- 19591549
TI  - Diagnosis and treatment of maternal acute myeloid leukemia during pregnancy
      imitating HELLP syndrome.

PMID- 19591550
TI  - Congenital cataract with de novo balanced reciprocal t(3;13) (q23;q12)
      translocation in a newborn.

PMID- 19591551
TI  - Vanishing nuchal translucency syndrome.

PMID- 19591552
TI  - Obstetric outcomes of low-risk labors at 'Japanese tatami' mat delivery room: a
      preliminary study.
AB  - OBJECTIVE: We examined the obstetric outcomes of low-risk labors at the 'Japanese
      tatami' mat compared with Western-style delivery room. METHODS: A retrospective
      cohort study was performed on 201 deliveries at the 'Japanese tatami' delivery
      room and 360 deliveries at the standard Western-style delivery room. RESULTS:
      There were no measurable differences in the duration of labor, the incidence of
      perineal laceration, total maternal blood loss and the incidence of low Apgar
      score and umbilical artery pH between the two groups. CONCLUSIONS: We found no
      evidence that the Japanese room is unsafe for low-risk infants and mothers in
      comparison with the standard Western-style delivery room.

PMID- 19591553
TI  - Reduction of IGF-binding protein-3 as a potential marker of intra-uterine growth
      restriction.
AB  - BACKGROUND: Growth factor-binding proteins influence the growth of infants
      starting in utero. Adaptation of the fetus to an adverse uterine environment is
      associated with changes in the growth hormone-growth factor-insulin axis. AIMS:
      To evaluate serum levels of IGF-I and IGFBP-3 in small and appropriate for
      gestational age newborn infants. METHODS: Fifty-four newborn infants, small (SGA,
      n=28) or appropriate (AGA, n=26) for gestational age were matched by gestational
      age and sex. Blood was collected on the first day of life, and anthropometric
      measurements were taken at birth. The serum levels of IGF-I and IGFBP-3 were
      compared, and correlated with the anthropometric measurements. RESULTS: On the
      first day of life, mean serum IGFBP-3 levels were significantly lower in SGA
      babies and correlated with weight, length, head circumference, and ponderal index
      (weight/length 3) (P<0.0001). In contrast, no associations were found between IGF
      I serum levels and these anthropometric measurements. CONCLUSION: Our data show
      that SGA babies have significantly reduced IGFBP-3 concentrations at birth.

PMID- 19591554
TI  - Nuchal translucency and lymphatic system maldevelopment.
AB  - We describe the histological examination of 18 aborted fetuses that had increased
      nuchal translucency (NT) between 11(+0) and 13(+6) weeks' gestation. The aim of
      this study was to assess the corresponding NT anatomic features by
      immunohistochemical (IHC) investigation. A morphological study was performed
      using lymphatic and blood endothelial specific markers, as well as smooth muscle
      actin (SMA). We found that all 18 cases were D2-40 positive, CD31 positive, and
      CD34 negative, suggesting the presence of nuchal lymph vessel ectasia. We found
      that 12/18 cases were SMA staining positive and 6/18 cases were SMA negative,
      suggesting that 6/18 cases had nuchal cystic lymphangiectasia, whereas 12/18 had
      cystic hygromas. The present data seem to confirm the reasonable hypothesis that
      lymphangiogenesis plays a relevant role in nuchal edema, increased NT, and that
      increased NT is the result of a lymphatic malformation or a delayed development
      of the lymphatic system.

PMID- 19591555
TI  - The clinical outcomes of late preterm infants: a multi-center survey of Zhejiang,
      China.
AB  - OBJECTIVE: To explore birth rate, delivery mode, medical problems, requirement of
      respiratory support, and acute outcomes of late preterm infants in Zhejiang
      province in eastern China. METHODS: Eleven tertiary hospitals were recruited.
      Clinical data of every nursery admission from January to December 2007 were
      collected and analyzed. RESULTS: During the study period, 44,362 infants were
      born with an overall preterm birth rate of 8.9%, and late preterm birth rate of
      6.2%. Late preterm infants had higher cesarean section rate than the whole
      population (64.9% vs. 58.2%). One-fifth of the nursery admissions were late
      preterm infants, of whom, 63.8% were delivered by cesarean section. Respiratory
      distress (42.1%) was the most common medical problem of late preterm infants.
      Hyperbilirubinemia (17.6%), hypoglycemia (8.7%) and sepsis (5.9%) were also
      common. The first three primary diagnoses of respiratory distress included
      pneumonia (39.5%), transient tachypnea of newborn (TTN) (22.5%) and respiratory
      distress syndrome (RDS) (19.0%). Compared with term infants, late preterm infants
      with respiratory distress needed more respiratory support with nasal continuous
      positive airway pressure (nCPAP) (21.4% vs. 11.6%) or with a mechanical
      ventilator (15.4% vs. 11.0%), and also had higher in-hospital mortality (0.8% vs.
      0.4%). CONCLUSIONS: Late preterm infants are associated with very high cesarean
      section rate and have more medical problems and poorer short-term outcomes than
      term infants in China.

PMID- 19591556
TI  - Disparity in circulating adiponectin multimers between term and preterm infants.
AB  - AIMS: To study circulating levels and distribution of adiponectin multimers [low
      molecular weight (LMW)-, medium molecular weight (MMW)- and high molecular weight
      (HMW)-adiponectin] in preterm and full-term infants. METHODS: Total serum
      adiponectin and its multimers were measured in 40 healthy infants at the age of
      one month and associations with anthropometric parameters [body weight and
      length, body mass index (BMI)], weight gain and metabolic indices (glucose,
      insulin) were examined. Twenty of the infants were born preterm (gestational age
      33.2+/-1.6 weeks). RESULTS: LMW-adiponectin level and its fractional ratio to
      total adiponectin were significantly higher in full-term than in preterm infants
      (P<0.001 and P<0.01, respectively), whereas, MMW-adiponectin level and its ratio
      were significantly lower (P=0.03 and P=0.01, respectively). HMW-adiponectin did
      not differ significantly between full-term and preterm infants and accounted for
      almost 60% of total adiponectin levels in both groups. HMW-adiponectin, but not
      MMW adiponectin or LMW adiponectin, correlated significantly with anthropometric
      measurements, similarly to total adiponectin; in addition, HMW adiponectin
      correlated significantly with weight gain. CONCLUSIONS: HMW adiponectin is the
      most prevalent form in infants. Circulating levels and distribution of MMW- and
      LMW-adiponectin differ between full-term and preterm infants, but the role of
      these adiponectin multimers needs to be studied further.

PMID- 19591558
TI  - Risk assessment for preeclampsia in women with gestational diabetes mellitus.
AB  - AIM: To develop a clinical model to assess the risk of preeclampsia in women with
      gestational diabetes mellitus (GDM). METHODS: We studied clinical characteristics
      of 813 consecutive women who had GDM between January 2003 and February 2008 at
      our institution. The clinical features which were significantly associated with
      preeclampsia by multiple logistic regression analysis were integrated into a risk
      model. The diagnostic performance of this model was then evaluated from a
      receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 78
      women with GDM (9.6%) developed preeclampsia. In a multivariable analysis, first
      trimester BMI > or =27 kg/m(2) (P<0.001), GDM diagnosed within 20 weeks of
      gestation (P<0.001), and poor glycemic control (P<0.001) were associated with
      preeclampsia. These three factors were incorporated into a risk-scoring model
      which ranged from 0 to 3 points. At the optimal cut-off score of > or =2, the
      sensitivity, specificity, and area under the curve (AUC) for preeclampsia were
      high at 76.9% [95% confidence interval (CI) 69.0-85.2], 92.8% (95% CI 85.9-98.1),
      and 0.849 (95% CI 0.792-0.905), respectively. CONCLUSION: A model based on
      clinical data yielded predicted the development of preeclampsia in women with
      GDM.

PMID- 19591559
TI  - The effect of maternal obesity on the course of labor.
AB  - AIM: To determine whether maternal obesity is associated with dysfunctional labor
      patterns. METHODS: In a case-control design we compared the graphic labor
      patterns of a group of 105 very obese subjects [body mass index (BMI) >35
      kg/m(2)] with those of 113 lean controls (BMI<26 kg/m(2)). All entered
      spontaneous labor at term. Cases with birth weights >4 kg, diabetes mellitus,
      hypertension and prior cesarean delivery were excluded. RESULTS: The obese group
      had a significantly higher frequency of arrest of dilatation (17.6 vs. 5.2%;
      P=0.005). CONCLUSIONS: Maternal obesity is associated with active phase labor
      dysfunction, specifically arrest of dilatation.

PMID- 19591560
TI  - What women want: psychodynamics of women's sexuality in 2008.
AB  - Sexual differentiation of the brain and behavior occurs as the result of prenatal
      hormonal influences. The fact that the brain is gendered from before birth means
      that psychodynamic paradigms of women's development must be modernized. This
      article discusses extra-analytic observations that we need to consider in
      constructing an up-to-date psychodynamic theory of women's sexuality.

PMID- 19591561
TI  - Dynamic psychopharmacology and treatment adherence.
AB  - Abstract The practice patterns of US psychiatrists have changed over the last two
      decades, favoring brief clinical encounters and a primary emphasis on
      pharmacologic care. The main focus of this paper is to illustrate the relevance
      of psychodynamic principles to prescribing practices. Psychodynamic aspects of
      pharmacotherapy will be described, including the dynamics of treatment adherence
      and nonadherence, medication selection, discontinuation, as well as aspects of
      transference and countertransference relevant to the practice of
      psychopharmacology. The dynamics of medication choice, underprescribing, and
      overprescribing will be reviewed to highlight the importance of psychodynamically
      informed psychopharmacology in the care of psychiatric patients. Special emphasis
      will be given to the contributions of attachment theorists to our understanding
      of treatment adherence. Psychoanalysts and dynamic psychiatrists are in a unique
      position to enhance psychopharmacologic case management by exploring the
      unconscious determinants of behavior.

PMID- 19591562
TI  - The dynamic psychiatrist: internist of the mind.
AB  - Abstract As dynamic psychiatrists our main clinical focus is to understand
      patients' symptoms and character structure through the exploration of their past
      and present experiences. This occurs within the context of their biopsychosocial
      environment. We work with tools such as free association, interpretation of
      transference distortions, and resistance to retrieving unconscious experiences.
      Yet, in the past 30 years our understanding of the role of the therapeutic
      relationship and other curative factors has changed. Through personal experience,
      the author explores these matters, considering more active participation in the
      treatment sessions, flexible frequency of meetings, modified use of therapeutic
      techniques, variable length of treatments, and concomitant use of psychotropic
      medication. More than in the past, the practice of the dynamic psychiatrist is
      modeled on that of the internist-a physician who integrates into his/her clinical
      work the current understanding of the function of the brain. The dynamic
      psychiatrist actively participates in the resolution of a given symptom picture
      and fosters improvement of the patient's personality structure to maximize
      functioning.

PMID- 19591563
TI  - Combined psychotherapies: searching for an order of operations in a disordered
      world.
AB  - Abstract Recent studies of psychotherapy demonstrate that therapists of different
      orientations-psychodynamic, cognitive-behavioral, interpersonal, and dialectical
      behavioral-provide beneficial treatment. Despite the stated adherence of
      clinicans to one orientation or another, review of session transcripts reveals a
      substantial overlap in the techniques utilized. Nonspecific or patient factors
      are the chief determinants of how therapy is conducted in practice. Nevertheless,
      the psychodynamic orientation offers the most comprehensive approach to therapy
      because it considers unconscious factors, including transference, enactments, and
      aspects of the patient's personal relationships. The psychodynamic formulation
      indicates the basis for determing how psychotherapy might best be conducted for
      the specific patient.

PMID- 19591564
TI  - Implications of the current insolubility of the mind-brain problem for the
      contemporary practice of psychodynamic psychiatry.
AB  - Abstract Even in this so-called era of the brain, there has been no consensual
      agreement on understanding the genesis of the mind by the brain, the problem that
      also baffled Freud, the neurologist at the start of his great discoveries.
      Especially, there has been no progress in solving what is known as the "hard
      problem," namely, how neurophysiological processes in the brain can produce
      conscious experiences, feelings, and intentions that constitute the "qualia," the
      various aspects of the phenomena of consciousness. Some of the predominant
      contemporary positions on the mind-brain problem, from Freud's Project for a
      Scientific Psychology to the present day, will be described and some of the
      technical vocabulary will be explained. I will conclude from this review that the
      "mysterian" position or some derivatives of it such as "anomalous monism" or
      "agnostic materialism" are probably the most plausible, given the present state
      of our knowledge and capacities. The latter two positions suggest that we simply
      do not know enough about the physical world of matter at this time but eventually
      perhaps discoveries about the nature of matter may solve the problem. But as of
      now, the implication of this impasse is that the introspective data of
      consciousness are ontologically subjective, pointing to the absolute necessity
      for our studying this data in its own domain through introspection. The most
      meticulous and thorough method for this study is psychoanalytic psychiatry, which
      was specifically devised by Freud for that purpose.

PMID- 19591565
TI  - Delineating prototypes of training psychotherapy.
AB  - Abstract There is no reported research comparing psychotherapy for trainees to
      psychotherapy for clinical patients. This preliminary study examines similarities
      and differences between the Training Psychotherapy Experience (TPE), an elective
      offered to residents in a large psychiatry training program, and psychotherapy
      conducted by the same clinicians in their private practices (TAU). We used the
      Psychotherapy Process Q-set (PQS; Ablon & Jones, 1988; Ablon, Levy, &
      Katzenstein, 2006). All program consultants who perform TPE were offered their
      standard fee to complete one PQS while envisioning a typical TPE session and
      another while envisioning a typical TAU session, using their own assessment of
      what happens in such sessions. These data were subjected to factor analysis to
      develop prototypes (TAU and TPE) that could be compared with each other and with
      validated prototypes developed by Ablon and Jones (1998, 2002). Twenty-two of the
      25 clinicians who perform TPE (88%) responded to the study. We found two distinct
      prototypes in both TPE and TAU. One correlated significantly with Ablon and
      Jones' Cognitive-Behavioral and Interpersonal prototypes, and the other with
      their Psychodynamic prototype. There was no significant difference between
      corresponding TPE and TAU prototypes. We conclude, first, TPE offers trainees an
      experience of psychotherapy that is very similar to psychotherapy of actual
      patients. Second, experienced clinicians integrate a broad array of useful
      interventions into both TPE and TAU.

PMID- 19591566
TI  - A view from Riggs: treatment resistance and patient authority--X: from acting out
      to enactment in treatment resistant disorders.
AB  - Abstract Patients with treatment resistant disorders pose a major problem to
      clinicians of all theoretical perspectives, including psychodynamic therapists.
      Treatment of such patients often results in stalemates and impasses, and acting
      out is a frequent phenomenon. This paper addresses the value in work with such
      patients of looking beyond the concept of acting out, which is a one-person
      definition of a problem, toward the concept of enactment, which recognizes the
      roles both therapist and patient play in the phenomenon of treatment resistance.

PMID- 19591568
TI  - Serum proinflammatory cytokine - interleukin-8 as possible infection site marker
      in preterm deliveries.
AB  - AIM: To evaluate serum level of proinflammatory cytokine interleukin-8 as a
      biochemical marker of local infections in patients with clinical symptoms of
      preterm deliveries. METHODS: We studied 74 pregnant women at 24-36 gestational
      weeks (GW) with preterm delivery. Serum interleukin-8 was measured. RESULTS: The
      mean value of interleukin-8 in the study group (n=36) was 19.13 pg/mL vs. 5.02
      pg/mL in the controls (n=38). CONCLUSIONS: The results indicate that serum level
      of interleukin-8 might be used as non-invasive marker of infections in pregnancy,
      as well as a marker of preterm deliveries.

PMID- 19591569
TI  - The infant incubator in the neonatal intensive care unit: unresolved issues and
      future developments.
AB  - Since the 19th century, devices termed incubators were developed to maintain
      thermal stability in low birth weight (LBW) and sick newborns, thus improving
      their chances of survival. Remarkable progress has been made in the production of
      infant incubators, which are currently highly technological devices. However,
      they still need to be improved in many aspects. Regarding the temperature and
      humidity control, future incubators should minimize heat loss from the neonate
      and eddies around him/her. An unresolved issue is exposure to high noise levels
      in the Neonatal Intensive Care Unit (NICU). Strategies aimed at modifying the
      behavior of NICU personnel, along with structural improvements in incubator
      design, are required to reduce noise exposure. Light environment should be taken
      into consideration in designing new models of incubators. In fact, ambient NICU
      illumination may cause visual pathway sequelae or possibly retinopathy of
      prematurity (ROP), while premature exposure to continuous lighting may adversely
      affect the rest-activity patterns of the newborn. Accordingly, both the use of
      incubator covers and circadian lighting in the NICU might attenuate these
      effects. The impact of electromagnetic fields (EMFs) on infant health is still
      unclear. However, future incubators should be designed to minimize the EMF
      exposure of the newborn.

PMID- 19591570
TI  - Survival and major disability rate in infant born at 22-25 weeks of gestation.
AB  - Our aim was to evaluate the literature on survival and major disability rate in
      preterm infants born at 22- 25 weeks of gestational age (GA). Thirty-three
      studies were identified and reviewed. Survival was lower in population-based
      studies (2% at 22, 13% at 23, 35% at 24, and 56% at 25 weeks) than in center
      based study (15% at 22, 41% at 23, 58% at 24, and 74% at 25 weeks). The severe
      disability rate was slightly higher in population-based studies than in center
      based studies at 23 (29 vs. 32%) and at 24 (30 vs. 27%) week of GA, whereas it
      was similar in population and center-based studies at 25 (21 vs. 22%) weeks of
      GA. Survival rate seems to improve with time, whereas the change of severe
      disability rate cannot be adequately evaluated due to the paucity of available
      data. We conclude that the survival of infants born at 22 weeks is still an
      uncommon event, whereas the survival of infants born at 23, and mostly at 24 and
      25 weeks of GA is significant in the majority of studies.

PMID- 19591571
TI  - Power to detect the effects of HIV vaccination in repeated low-dose challenge
      experiments.
AB  - Simulation studies were conducted to estimate the statistical power of repeated
      low-dose challenge experiments performed in nonhuman primates to detect the
      effect of a candidate human immunodeficiency virus vaccine. The effect of various
      design parameters on power was explored. Results of simulation studies indicate
      that repeated low-dose challenge studies with a total sample of size 50 (25
      animals/arm) typically provide adequate power to detect a 50% reduction in the
      per-exposure probability of infection resulting from vaccination. Power generally
      increases with the maximum number of allowable challenges per animal, the per
      exposure risk of infection in control animals, and the proportion of animals
      susceptible to infection.

PMID- 19591572
TI  - Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive
      HIV-infected subjects.
AB  - Because both renal disease and immune activation predict progression to acquired
      immunodeficiency syndrome (AIDS), we evaluated the associations between
      proteinuria>or=1+, as determined by dipstick analysis (7 [7%] of 1012 subjects);
      creatinine clearance of <90 mL/min (195 [18%] of 1071 subjects); and percentages
      of peripheral activated CD8 cells (CD8+CD38+HLA-DR+ cells) in antiretroviral
      naive, human immunodeficiency virus (HIV)-infected subjects who were enrolled in
      AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not creatinine
      clearance, was associated with higher percentages of CD8+CD38+HLA-DR+ cells (55%
      vs. 50%; P=.01), with even more pronounced differences noted among men and among
      blacks and Hispanics. Proteinuria may be a surrogate measurement of greater
      immune activation in HIV-infected patients initiating antiretroviral therapy.

PMID- 19591573
TI  - Essential role for neutrophils but not alveolar macrophages at early time points
      following Aspergillus fumigatus infection.
AB  - Alveolar macrophages and neutrophils mediate innate immune defense against the
      opportunistic fungal pathogen Aspergillus fumigatus and are believed to be
      essential for host survival following inhalation of fungal spores (conidia).
      Although alveolar macrophages are postulated to kill inhaled conidia and
      neutrophils are believed to act against hyphae, the relative contribution of
      alveolar macrophages and neutrophils to early defense against A. fumigatus remain
      incompletely defined. To more precisely characterize the contributions of
      alveolar macrophages and neutrophils in antifungal host defense, we selectively
      depleted each cell population at different times following pulmonary challenge
      with conidia. Mice depleted of alveolar macrophages prior to pulmonary A.
      fumigatus infection recruited neutrophils normally and restricted hyphal tissue
      invasion. In contrast, neutrophil depletion prior to or within 3 h after
      infection was associated with high mortality. Neutrophil depletion at later time
      points, however, was associated with nearly normal survival rates. Our studies
      suggest that neutrophils, but not alveolar macrophages, provide essential
      anticonidial defense and that a brief period of influx into the respiratory tree
      is sufficient to prevent conidial germination and invasive disease.

PMID- 19591574
TI  - Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical
      Streptococcus pyogenes infection.
AB  - Neutrophil chemoattractant interleukin (IL)-8 is cleaved and inactivated by the
      Streptococcus pyogenes cell envelope protease SpyCEP. A range of clinical S.
      pyogenes strains of differing emm type demonstrated SpyCEP activity, although
      transcription of the SpyCEP gene cepA differed 1000-fold between isolates.
      Disruption of the 2-component regulatory system covR/S in pharyngeal isolates
      increased cepA transcription 100-fold; this finding is consistent with endogenous
      CovR/S-mediated repression of cepA being responsible for low SpyCEP expression in
      some S. pyogenes strains associated with pharyngitis. Among patients with
      invasive S. pyogenes infection, disease severity and outcome were associated with
      the SpyCEP activity of the isolate. Lethal invasive isolate H292 (emm81)
      expressed more cepA than did other tested isolates. This strain carried a unique
      covR mutation that impaired binding to the cepA promoter. CovR/S sequence
      comparison in other clinical isolates revealed community-wide dissemination of
      covS mutations but not covR mutations. The results highlight a potential hazard
      and underline the importance of continuing molecular epidemiological surveillance
      for community-wide dissemination of CovR/S mutant hyperinvasive strains.

PMID- 19591575
TI  - Viral loads and duration of viral shedding in adult patients hospitalized with
      influenza.
AB  - BACKGROUND: The goal of this study was to characterize viral loads and factors
      affecting viral clearance in persons with severe influenza. METHODS: This was a 1
      year prospective, observational study involving consecutive adults hospitalized
      with influenza. Nasal and throat swabs were collected at presentation, then daily
      until 1 week after symptom onset. Real-time reverse-transcriptase polymerase
      chain reaction to determine viral RNA concentration and virus isolation were
      performed. Viral RNA concentration was analyzed using multiple linear or logistic
      regressions or mixed-effect models. RESULTS: One hundred forty-seven inpatients
      with influenza A (H3N2) infection were studied (mean age+/-standard deviation,
      72+/-16 years). Viral RNA concentration at presentation positively correlated
      with symptom scores and was significantly higher than that among time-matched
      outpatients (control subjects). Patients with major comorbidities had high viral
      RNA concentration even when presenting>2 days after symptom onset (mean+/
      standard deviation, 5.06+/-1.85 vs 3.62+/-2.13 log10 copies/mL; P=.005; beta,
      +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration
      demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57%
      of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir
      started on or before symptom day 4 was independently associated with an
      accelerated decrease in viral RNA concentration (mean beta [standard error], 
      1.19 [0.43] and -0.68 [0.33] log10 copies/mL for patients treated on day 1 and
      days 2-3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio,
      0.10 [95% confidence interval, 0.03-0.35] and 0.30 [0.10-0.90] for patients
      treated on day 1-2 and day 3-4, respectively). Conversely, major comorbidities
      and systemic corticosteroid use for asthma or chronic obstructive pulmonary
      disease exacerbations were associated with slower viral clearance. Viral RNA
      clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001).
      CONCLUSION: Patients hospitalized with severe influenza have more active and
      prolonged viral replication. Weakened host defenses slow viral clearance, whereas
      antivirals started within the first 4 days of illness enhance viral clearance.

PMID- 19591576
TI  - Misclassification of drug failure in Plasmodium falciparum clinical trials in
      southeast Asia.
AB  - Most trials of antimalarials occur in areas in which reinfections are possible.
      For Plasmodium falciparum, reinfections are distinguished from recrudescences by
      polymerase chain reaction analysis of 3 polymorphic genes. However, the validity
      of this approach has never been rigorously tested. We tested for
      misclassification in 6 patients from clinical trials in Thailand and Cambodia who
      were classified as being reinfected by the standard polymerase chain reaction
      protocol. Using heteroduplex tracking assays and direct DNA sequencing, we found
      that 5 (83%) of 6 patients were misclassified. Misclassification in this manner
      overestimates the efficacy of antimalarials and delays the recognition of
      decreasing therapeutic efficacy, thus delaying potential changes in policy.

PMID- 19591577
TI  - MIF (macrophage migration inhibitory factor) promoter polymorphisms and
      susceptibility to severe malarial anemia.
AB  - BACKGROUND: Severe malarial anemia (SMA) resulting from Plasmodium falciparum
      infection is one of the leading causes of childhood mortality in sub-Saharan
      Africa. The innate immune mediator macrophage migration inhibitory factor (MIF)
      plays a critical role in the pathogenesis of SMA. METHODS: To investigate the
      influence of MIF genetic variation on susceptibility to SMA, haplotypes of the
      MIF -173G/C and -794CATT5-8 polymorphisms were examined in a cohort of Kenyan
      children. RESULTS: A statistically significant relationship between increasing
      frequencies of longer CATT repeats at -794 and increasing severity of malarial
      anemia was observed. In addition, there was a strong association between lower
      MIF concentrations and longer CATT repeats. Multivariate logistic regression
      analyses demonstrated that the 6G haplotype (ie, MIF -794CATT6/-173G) was
      associated with protection against SMA, whereas carriers of the 7C or 8C
      haplotype had increased risk of developing SMA. Furthermore, carriers of the 7C
      or 8C haplotype had reduced plasma MIF levels during acute disease. CONCLUSIONS:
      The findings demonstrate that variation in the MIF promoter influences
      susceptibility to SMA and peripheral MIF production. However, the MIF -173 and 
      794 polymorphisms appear to have both independent and interactive effects on
      different measures of disease severity, suggesting that MIF plays a complex role
      in malarial pathogenesis.

PMID- 19591578
TI  - Influenza in hospitalized adults: gaining insight into a significant problem.

PMID- 19591579
TI  - Risk parameters of fulminant acute respiratory distress syndrome and avian
      influenza (H5N1) infection in Vietnamese children.
AB  - A clinical picture of patients with acute respiratory distress syndrome (ARDS)
      induced by highly pathogenic avian influenza A (H5N1) has been reported. We
      reviewed 37 sets of clinical data for pediatric patients with ARDS at the
      National Hospital of Pediatrics (Hanoi, Vietnam); 12 patients with H5N1-positive
      and 25 with H5N1-negative ARDS were enrolled. The H5N1-negative patients had a
      clinical picture and mortality rate similar to that for the pediatric ARDS
      patients. However, the H5N1-positive patients had ARDS with normal ventilation
      capacity at the time of hospital admission, then rapidly proceeded to severe
      respiratory failure. The survival probability and days until final outcome in
      groups of H5N1-positive (n=12) vs. H5N1-negative (n=25) patients were 17% versus
      52% and 12.3+/-5.7 days (median, 11 days) versus 21.5+/-13.8 days (median, 22
      days), respectively. Our observations clarified the clinical picture of H5N1
      induced fulminant ARDS and also confirmed that relatively older age
      (approximately 6 years of age), high fever at onset, and leukopenia and/or
      thrombocytopenia at the time of hospital admission are risk parameters for H5N1
      induced fulminant ARDS.

PMID- 19591580
TI  - Epidemiology of methicillin-resistant Staphylococcus aureus bacteremia in
      Gaborone, Botswana.
AB  - This cross-sectional study at a tertiary-care hospital in Botswana from 2000 to
      2007 was performed to determine the epidemiologic characteristics of
      Staphylococcus aureus bacteremia. We identified a high prevalence (11.2% of
      bacteremia cases) of methicillin-resistant S. aureus (MRSA) bacteremia. MRSA
      isolates had higher proportions of resistance to commonly used antimicrobials
      than did methicillin-susceptible isolates, emphasizing the need to revise empiric
      prescribing practices in Botswana.

PMID- 19591581
TI  - Vancomycin-resistant enterococci in long-term care facilities.
AB  - Knowledge of the prevalence rates and associated risk markers of vancomycin
      resistant enterococci (VRE) colonization among long-term care facility (LTCF)
      residents could be used to improve screening policies among newly admitted
      hospital inpatients. In a cross-sectional survey among 1,215 residents of LTCFs
      in Jerusalem, the VRE carriage rate was 9.6%. Previous hospitalization and
      antibiotic treatment were associated with elevated VRE colonization rate. In
      contrast, moderate and severe levels of dependency and prolonged stay in an LTCF
      were associated with a decrease in the VRE colonization rate.

PMID- 19591582
TI  - Colonization with Staphylococcus aureus and methicillin-resistant S. aureus among
      a sample of homeless individuals, Ohio.

PMID- 19591583
TI  - Ethical analysis of communicating the risk of iatrogenic Creutzfeldt-Jakob
      disease.

PMID- 19591584
TI  - Health-related quality of life after intensive care unit discharge: A comparison
      between 2 standard antibiotic regimens.

PMID- 19591585
TI  - Searching many guidelines for how best to control methicillin-resistant
      Staphylococcus aureus healthcare-associated spread and infection.

PMID- 19591586
TI  - The art and science of influencing hand hygiene.

PMID- 19591588
TI  - Effect of chlorhexidine probably overestimated because of lack of neutralization
      after sampling.

PMID- 19591590
TI  - Emerging evidence for seasonality of gram-negative bacterial infections.

PMID- 19591593
TI  - Correlates and prognostic value of the first-phase hepatitis C virus RNA kinetics
      during treatment.
AB  - BACKGROUND: Analysis of hepatitis C virus (HCV) RNA kinetics during antiviral
      therapy may allow estimation of the probability of response. METHODS: To assess
      clinical and virological correlates and the predictive value of first-phase HCV
      RNA kinetics during pegylated interferon and ribavirin treatment, we studied 119
      patients with chronic hepatitis C who were treated with pegylated interferon and
      ribavirin. HCV RNA level was measured 5 min before and 2, 14, and 28 days after
      the start of treatment. For each patient the Delta(t0-t2) log(10) HCV RNA value
      was calculated, which indicates the relative reduction in HCV RNA level from
      before treatment to day 2 after logarithmic transformation. RESULTS: A Delta(t0
      t2) log(10) HCV RNA value < or =0.8 showed a 95% negative predictive value for
      virological response, whereas one >2.5 had a 93% positive predictive value for
      virological response, independent of genotype and histology. The Delta(t0-t2)
      log(10) HCV RNA value was strictly related to final treatment outcome and could
      differentiate not only patients with a sustained virological response from
      nonresponders but also patients who experienced relapse from the former. The
      Delta(t0-t2) log(10) HCV RNA value was highest among patients infected with
      genotypes 2 and 3 and was lowest among patients infected with genotype 1. It
      decreased with increasing grades of fibrosis and steatosis and was also inversely
      related to gamma-glutamyl transpeptidase (GGT) level and HOMA-IR (homeostasis
      model assessment for insulin resistance) score. In multivariate analysis,
      Delta(t0-t2) log(10) HCV RNA value was the strongest predictor of sustained
      virological response and appeared to be independently related to viral genotype
      and GGT level. CONCLUSION: HCV RNA kinetics has strong predictive value. It
      correlates with virological and clinical parameters that are known predictors of
      antiviral treatment outcome, including insulin resistance. The measurement of HCV
      load as early as 2 days after the start of pegylated interferon and ribavirin is
      a useful tool for the prediction of treatment outcome in individual patients and
      should be used in clinical practice.

PMID- 19591594
TI  - Coinfection with hepatitis C virus and HIV: more than double trouble.

PMID- 19591595
TI  - Serodiagnostic contributions of antibody titers against mycobacterial lipid
      antigens in Mycobacterium avium complex pulmonary disease.
AB  - BACKGROUND: Although the incidence of pulmonary tuberculosis is decreasing, the
      number of immunocompetent patients with Mycobacterium avium complex (MAC)
      pulmonary disease is steadily increasing. Therefore, albeit not contagious, MAC
      pulmonary disease needs to be diagnosed rapidly and accurately. We examined the
      serodiagnostic contributions of serum immunoglobulin G antibody titers against
      the species-specific and -common mycobacterial lipid antigens in the diagnosis of
      MAC pulmonary disease. METHODS: Serum samples were obtained from 65 patients with
      MAC pulmonary disease, 15 patients with suspected MAC disease, 25 patients with
      pulmonary tuberculosis, 10 patients with Mycobacterium kansasii disease, and 100
      healthy volunteers (control subjects). We measured the serum immunoglobulin G
      antibody titers against trehalose monomycolate (TMM-M) and apolar
      glycopeptidolipid (GPL), lipid antigens extracted from MAC. RESULTS: In patients
      with MAC pulmonary disease, the antibody titers against TMM-M and apolar-GPL were
      significantly higher than those in the other patient groups or in the control
      subjects. By receiver operator characteristic curve analysis, an optical density
      of 0.27, corresponding to the optimal cutoff antibody titer against TMM-M, was
      associated with a sensitivity of 89.2% and a specificity of 97.0%, and an optical
      density of 0.33, corresponding to the optimal cutoff antibody titer against
      apolar-GPL, was associated with a sensitivity of 89.2% and a specificity of
      94.0%. CONCLUSIONS: Measurements of antibody titers against TMM-M and apolar-GPL
      would be useful in the diagnosis of MAC pulmonary disease and in the differential
      diagnosis of mycobacterial pulmonary disease.

PMID- 19591596
TI  - Prediction of complicated Clostridium difficile infection by pleural effusion and
      increased wall thickness on computed tomography.
AB  - BACKGROUND: Abdominal computed tomography (CT) is often used to evaluate
      complications in patients with Clostridium difficile infection (CDI), but no
      study has correlated CT findings with the risk of developing a complicated CDI.
      Furthermore, the value of CT has not been evaluated since the emergence of the
      BI/NAP1/027 hypervirulent strain of C. difficile. We sought to describe and
      correlate abdominal CT findings with complicated CDI and to compare them before
      and after the emergence of the epidemic strain. METHODS: We conducted a
      retrospective cohort study of all hospitalized patients 18 years or older who,
      from 1 January 1998 through 31 December 2006, underwent abdominal CT within 72 h
      of their first positive stool sample. RESULTS: Of 1189 patients with newly
      diagnosed CDI, 165 satisfied the inclusion criteria. Patients who underwent CT
      were younger, had higher peak white blood cell counts and serum creatinine
      levels, and were more likely to experience fever than those who did not undergo
      CT. No difference in CT findings was noted before and after the emergence of
      BI/NAP1/027 CDI. Pleural effusion (adjusted odds ratio [AOR], 2.6; 95% confidence
      interval [CI], 1.1-6.6), colonic wall thickness >15 mm (AOR, 6.0; 95% CI, 1.1
      33.9), peak white blood cell count > or =30 x 10(9) cells/L (AOR, 4.8; 95% CI,
      1.4-16.4), albumin level <20 g/L (AOR, 6.9; 95% CI, 2.4-20.1), and
      immunosuppression (AOR, 4.7; 95% CI, 1.5-15.3) were independently associated with
      complicated CDI. CONCLUSIONS: In a selected sample of patients with CDI, CT
      provided prognostic information additional to what could be obtained from
      clinical and laboratory parameters. No change in CT characteristics was noted
      after the introduction of the BI/NAP1/027 strain in our center.

PMID- 19591598
TI  - A revolution in the identification of pathogens in clinical laboratories.

PMID- 19591600
TI  - Survival and quality of life among HIV-positive people on antiretroviral therapy
      in Cambodia.
AB  - In 2004, Cambodia, a low-income country, undertook a rapid scale-up of free
      antiretroviral therapy (ART) through the public sector in order to respond to the
      need for treatment for those living with HIV/AIDS. A cohort of patients
      initiating ART in a provincial national hospital was set up at the beginning of
      the program to monitor the impact of treatment on patients. Patients provided
      information on behaviors through face-to-face interviews. Medical data were
      obtained from clinical files. Health-related quality of life (HRQOL) was assessed
      using the Medical Outcomes Study 21-Items Short Form (MOS SF-21). Patients were
      interviewed when initiating ART and followed up at 3 months, 6 months, and each
      consecutive 6 months thereafter. From March 2005 through January 2008, the cohort
      included 549 patients followed for a total of 645 person-years. The 4.0% of
      patients lost to follow-up were considered dead in the analysis. Incidence of
      mortality was 9.1 per 100 person-years, which is comparable to international
      standards. HRQOL subscale scores increased dramatically in the first year after
      initiating ART. The mean of overall HRQOL score rose from 63.0 at baseline to
      81.1 at 1 year and 89.9 at 30 months of follow-up (chi(2) for trends p < 0.001).
      Simultaneously, the proportion of patients with full-time employment increased
      from 48.8% to 95.7%.We conclude that the rapid scaling-up of ART delivery in a
      resource poor Asian setting dramatically improved the survival and well-being of
      its beneficiaries, who in turn resumed productive lives within their communities.

PMID- 19591599
TI  - Invasive non-Typhi Salmonella disease in Africa.
AB  - Invasive non-Typhi Salmonella is endemic to sub-Saharan Africa, where it is a
      leading cause of bloodstream infection. Some host risk factors have been
      established, but little is known about environmental reservoirs and predominant
      modes of transmission, so prevention strategies are underdeveloped. Although
      foodborne transmission from animals to humans predominates in high-income
      countries, it has been postulated that transmission between humans, both within
      and outside health care facilities, may be important in sub-Saharan Africa.
      Antimicrobial resistance to ampicillin, trimethoprim-sulfamethoxazole, and
      chloramphenicol is common among non-Typhi Salmonella strains; therefore, wider
      use of alternative agents may be warranted for empirical therapy. Development of
      vaccines targeting the leading invasive non-Typhi Salmonella serotypes
      Typhimurium and Enteritidis is warranted. The clinical presentation of non-Typhi
      Salmonella bacteremia is nonspecific and, in the absence of blood culture, may be
      confused with other febrile illnesses, such as malaria. Much work remains to be
      done to understand and control invasive non-Typhi Salmonella disease in sub
      Saharan Africa.

PMID- 19591597
TI  - Risk of developing specific AIDS-defining illnesses in patients coinfected with
      HIV and hepatitis C virus with or without liver cirrhosis.
AB  - BACKGROUND: There are few data concerning the risk of specific opportunistic
      diseases in patients with and without hepatitis C virus (HCV) infection. We
      evaluated the correlation between the occurrence of different AIDS-defining
      illnesses (ADIs) and chronic HCV infection or HCV-related liver cirrhosis in a
      large Italian cohort of human immunodeficiency virus (HIV)-infected subjects.
      METHODS: Subjects were stratified into 2 groups: patients without HCV coinfection
      and with persistently normal aminotransferase levels and patients with HCV
      coinfection. The patients with HCV coinfection were stratified according to the
      diagnosis of liver cirrhosis. The incidences of new ADIs were calculated as the
      number of events per 1000 person-years of follow-up. The rates in the 2 groups
      were compared using a Poisson regression model adjusted for potential
      confounders. RESULTS: We observed a total of 496 ADIs among 5397 patients with
      25,105 person-years of follow-up (50% tested positive for HCV). HCV coinfection
      was associated with increased risk of developing an ADI (adjusted relative rate
      [ARR], 2.61; 95% confidence interval [CI], 1.88-3.61), specifically bacterial
      infection (ARR, 3.15; 95% CI, 1.76-5.67), HIV-related disease (ARR, 2.68; 95% CI,
      1.03-6.97), and mycotic disease (ARR, 3.87; 95% CI, 2.28-6.59) but not non
      Hodgkin lymphoma (ARR, 0.88; 95% CI, 0.22-3.48). The rate of mycotic infection,
      bacterial infection, toxoplasmosis, and HIV-related ADI among patients with
      cirrhosis were significantly higher than that among HIV-monoinfected patients,
      and the risk was greater than that estimated for HCV antibody-positive patients
      without cirrhosis. CONCLUSIONS: HIV-related bacterial and mycotic infections are
      strongly associated with positive HCV serostatus and HCV-related cirrhosis.
      Clinicians should take into account these data when making decisions on
      initiation of antiretroviral therapy for HCV-coinfected individuals.

PMID- 19591602
TI  - Piloting a peer-driven intervention model to increase access and adherence to
      antiretroviral therapy and HIV care among street-entrenched HIV-positive women in
      Vancouver.
AB  - A peer-driven intervention (PDI) was developed to support uptake and adherence to
      highly active antiretroviral therapy (HAART) among women sex workers who use
      illicit substances in Vancouver, because uptake and adherence continues to be
      suboptimal. Trends of adherence were examined among women in this program by (1)
      exposure to the intervention and (2) risk behaviors including drug use and
      unstable housing. Between January 2007 and January 2008, 20 HIV-positive women
      were enrolled into the PDI on a rolling basis. PDI participation included weekly
      peer support meetings, a health advocate (buddy) system, peer outreach service,
      and onsite nursing care. Adherence was measured directly with pharmacy records
      (PR) and indirectly with self-report and viral load (VL) outcomes. Participants
      attended an average of 50 (21-70) PDI meetings. Overall self-reported adherence
      was high (92%) and most women (11) reported increased adherence from the first to
      the last 13 PDI meetings attended (average increase = 18%). The number of viral
      load tests <or=50 copies/mL increased by 40% from the pre-PDI period (1 year
      before enrollment), to the PDI period (duration enrolled). PR adherence and
      improvements in VL outcomes were higher among participants with greater housing
      instability and frequency of injecting/smoking drugs. Despite a very difficult
      environment to provide HIV care, there is evidence to suggest that the PDI may
      have had a positive impact on adherence outcomes. Although this would not predict
      long-term treatment success, the PDI approach to HIV treatment support is a
      promising program for women who might otherwise be excluded from treatment
      altogether.

PMID- 19591601
TI  - A comparison of adherence assessment methods utilized in the United States:
      perspectives of researchers, HIV-infected children, and their caregivers.
AB  - This study sought to elucidate methodological issues in adherence research by
      comparing multiple methods of assessing adherence to antiretroviral medication.
      From 2003 to 2004, 24 youths with vertically infected HIV disease (mean age =
      14.0 years; range, 8-18) and their caregivers participated in a 6-month study.
      These children were all on highly active antiretroviral therapy (HAART) and were
      relatively healthy (mean CD4 absolute count = 711.8 +/- 604.5). Adherence was
      assessed with the Medication Event Monitoring System (MEMS), pill counts, and
      interviews. Patients and caregivers completed the Perceptions of Adherence Study
      Participation (PASP) questionnaire. MEMS provided the most detailed adherence
      information, and good reliability was indicated by significant correlations with
      medical markers. Pill counts provided similar adherence rates, while patients and
      caregivers reported nearly perfect adherence in interviews. Problems were
      experienced with each method: MEMS were expensive, had cap malfunctions, and lack
      a consistent guiding principle for data interpretation. With pill counts,
      families forgot to bring all medication bottles to clinic, and interviews were
      compromised by social desirability and difficulty reaching families by telephone.
      Most patients and caregivers believed study participation improved the child's
      adherence, although PASP ratings were unrelated to adherence at the study
      endpoint. While MEMS may be most reliable, pill counts offer comparable data and
      are less costly, while interviews seemed least accurate in this study. Most
      participants reported positive perceptions of their research experience. A
      consensus among researchers is needed for defining and measuring adherence, and
      specific recommendations are offered for achieving this goal.

PMID- 19591603
TI  - Sexual risk behavior and behavior change among persons newly diagnosed with HIV:
      the impact of targeted outreach interventions among hard-to-reach populations.
AB  - The secondary effect of a national, targeted, outreach initiative in reducing
      sexual risk behavior among newly diagnosed persons living with HIV/AIDS (PLWHA)
      was examined in the present study. The findings propose an optimal number of
      outreach program contacts associated with a change in sexual risk behavior. The
      primary goal of the initiative was to implement and evaluate strategies to engage
      and retain underserved populations (PLWHA) in HIV primary medical care.
      Participants from 10 sites nationwide were enrolled in outreach interventions
      from 2004 to 2005 that were designed to engage and retain hard-to-reach PLWH in
      care. The study population in the subanalysis performed was predominantly male,
      people of color, sexual minorities; mean age of 32, and 31% reported no visits to
      an HIV health provider since testing positive. The study design was prospective
      and nonrandomized; 116 newly diagnosed individuals reported on unprotected sex at
      baseline, 6-, and 12-month interviews. The proportion of individuals reporting
      unprotected sex postintervention was reduced significantly compared to baseline.
      Postbaseline, individuals were 80% less likely to report unprotected sex.
      Additionally, individuals with 1-3 program contacts per month were 80 times less
      likely to report risky sexual behavior compared to those with 2 or less contacts
      (adjusted odds ratio [AOR] = 0.20). Substantial risk exists for secondary HIV
      transmission; this study shows the promise of a supplemental intervention to
      ensure access to HIV care, retention in care, and risk reduction for positives.

PMID- 19591604
TI  - Development of an HIV risk reduction intervention for older seropositive African
      American men.
AB  - The purpose of this study was to assess the feasibility and acceptability of an
      HIV risk reduction intervention to increase consistent condom use in a sample of
      older HIV-positive African American men who have sex with men (MSM). Repeated
      measures were used at baseline, immediate postintervention, and 3 months
      postintervention to collect data. The development of the intervention was
      implemented in four phases: focus groups, pilot testing of the questionnaire,
      modifying the intervention, and executing the intervention. Sixty HIV-positive
      African American MSM were randomized to either an HIV risk condition or a health
      condition. Each condition consisted of four 120-minute sessions delivered over a
      4-week period in a classroom-like setting using interactive approaches. The
      primary outcome was consistent condom use during every instance of anal
      intercourse. In unadjusted analyses, men in the risk reduction group were twice
      as likely to use condoms consistently (odds ratio [OR] = 2.04; 95% confidence
      interval [CI] = 0.48-8.77; p = 0.336), although this did not reach statistical
      significance. All participants reporting consistent condom use at baseline
      reported consistent use at 3 months giving perfect prediction for the sample.
      Among men not reporting consistent condom use at baseline, those in the risk
      reduction group were 5 times more likely to report consistent condom use at 3
      months than were those in the health condition (OR = 5.18; 95% CI = 0.97-27.78; p
      = 0.054). The findings suggest that an HIV risk-reduction condition may increase
      consistent condom use among HIV-positive African American MSM 50 years and older.

PMID- 19591605
TI  - Increasing early diagnosis of HIV through rapid testing in a street outreach
      program in Spain.
AB  - Our goal was to analyze the results of a multicity program offering rapid HIV
      testing in a mobile unit in central locations. Between October 2006 and December
      2007, 7138 persons were tested, providing a finger-prick blood sample and filling
      out a brief questionnaire while waiting for the results of the Determine((R))
      test. Seventy people were classified as reactive and 3 as indeterminate.
      Confirmatory test results were obtained for 83.6%. Of the 56 reactive persons
      contacted, 2 were confirmed as negative, giving a positive predictive value of
      96.6%. Those tested were primarily men (60.6%), persons with university education
      (47.4%), and included a large percentage of immigrants (26.2%), especially from
      Latin America, and 37.3% were men who have sex with men (MSM). Forty-seven
      percent had ever been tested for HIV. Global HIV prevalence was 0.98% (confidence
      interval [CI]: 0.75-1.21), 1.59%, (CI: 1.21-1.97) in men and 0.19%, (CI: 0.02
      0.35) in women. In the tree analysis the high prevalence node included Latin
      Americans with only primary studies (study level finished at least at the age of
      12). Of the 64% HIV-positive tests in 2007 with available CD4 counts, 18.75% had
      CD4 counts under 350. Street-based mobile units offering rapid HIV testing in
      selected sites, may diagnose HIV at an earlier stage of infection than clinic
      based sites, and have a low rate of false-positives.

PMID- 19591606
TI  - Routine opt-out HIV testing in an urban community health center.
AB  - Undiagnosed HIV infection remains a significant public health problem. To address
      this, the Centers for Disease Control and Prevention revised testing
      recommendations, calling for routine opt-out HIV screening among adults in health
      care settings. However, these recommendations have not been widely implemented in
      primary care settings. We examined acceptability of opt-out HIV testing in an
      urban community health center and factors associated with accepting testing. From
      July 2007 to March 2008, physicians or a designated HIV tester approached
      patients presenting for primary care visits during 52 clinical sessions at an
      urban community health center. Patients were told they "would be tested for HIV
      unless they declined testing." Enzyme-linked immunosorbent assays, which required
      venipuncture, were used to test for HIV infection. We extracted demographic,
      clinical, and visit characteristics from medical records and examined
      associations between these characteristics and accepting HIV testing using
      logistic regression. Of 300 patients, 35% agreed to HIV testing, with no new HIV
      infections detected. Common reasons for declining testing were perceived low risk
      (54.4%) and self-reported HIV testing previously (45.1%). Younger age (adjusted
      odds ratio [AOR] = 0.97, 95% confidence interval [CI] = 0.96-0.99), Hispanic
      ethnicity (AOR = 1.78, 95% CI = 1.01-3.14), and having another blood test during
      the visit (AOR = 6.36, 95% CI = 3.58-11.28) were independently associated with
      accepting HIV testing. This study questions whether expanding HIV testing by
      conducting routine opt-out HIV testing in primary care settings is an acceptable
      strategy. It is important to understand how various testing strategies may affect
      HIV testing rates. In addition, further exploration of patients' reasons for
      declining HIV testing in these settings is warranted.

PMID- 19591607
TI  - Stigma, disclosure, and depressive symptoms among informal caregivers of people
      living with HIV/AIDS.
AB  - Informal care receipt is associated with better HIV treatment outcomes among
      patients vulnerable to treatment failure. Yet, informal caregiving can be highly
      stressful, leading to distress and cessation of caregiving. Research on factors
      contributing to informal caregivers' psychological distress may advance our
      understanding of how to improve caregivers' well-being and sustained HIV
      caregiving for a vulnerable population. We examined relationships among caregiver
      stigma, disclosure, and depressive symptoms in a cross-sectional sample of 207
      informal caregivers of people living with HIV/AIDS (PLWHAs) in Baltimore,
      Maryland. Caregivers were primarily African American, low-income, urban adults
      participating in the Action, Resources, and Knowledge (ARK) study (2003-2005),
      which recruited urban PLWHAs and their main supporters. Results indicated that
      among caregivers, HIV caregiving-related stigma was associated with more
      depressive symptoms, while disclosure of caregiving status was associated with
      fewer symptoms. We also explored the buffering effect of disclosure in the
      relationship between stigma and depressive symptoms. Results indicated that among
      those who reported greater stigma, there was a significant decrease in depressive
      symptoms as the number of disclosures increased. In contrast, participants who
      indicated lower stigma had consistently fewer depressive symptoms regardless of
      number of disclosures. These results suggest the need for interventions to
      address high levels of depressive symptoms among informal HIV caregivers,
      particularly those who report greater caregiving stigma and less disclosure of
      their caregiver status. In addition, future research should examine these
      relationships further using longitudinal data from informal caregivers and their
      care recipients.

PMID- 19591608
TI  - The prevalence of rectal, urethral, and pharyngeal Neisseria gonorrheae and
      Chlamydia trachomatis among asymptomatic men who have sex with men in a
      prospective cohort in Washington, D.C.

PMID- 19591609
TI  - Renal function in patients with preexisting renal disease receiving tenofovir
      containing highly active antiretroviral therapy in the HIV outpatient study.
AB  - Few data exist on the safety of tenofovir (TDF) in HIV-infected patients with
      preexisting renal dysfunction. We report 12-month changes in renal profiles among
      19 such patients (6 patients with history of and 13 patients with current renal
      disease) in the HIV Outpatient Study (HOPS) who initiated TDF-containing highly
      active antiretroviral therapy (HAART) during 2001-2005 with TDF dosed mostly at
      300 mg once daily. At baseline, the median estimated glomerular filtration rate
      (GFR) was 49 mL/min/1.73 m(2) and the median CD4(+) cell count was 322
      cells/mm(3). Patients had a median 12-month change in estimated creatinine
      clearance from baseline of -0.3 mL/min (range, -32.2 to +23.6) and the median
      change in GFR of -0.1 mL/min/1.73 m(2) (range, -49.8 to +29.5). We observed
      confirmed worsening of kidney disease stage in 5 of the 19 patients during follow
      up. TDF use can be considered in patients with preexisting or current renal
      dysfunction who have limited antiretroviral treatment options, require TDF for
      fully active antiretroviral regimen, and can be closely monitored for incident
      worsening of renal function.

PMID- 19591610
TI  - At-risk drinking and injection and sexual risk behaviors of HIV-positive
      injection drug users entering drug treatment in New York City.
AB  - We analyzed data from 1253 HIV-positive injection drug users (IDUs) entering
      detoxification or methadone maintenance treatment in New York City between 1990
      and 2004 to assess HIV risk behaviors and their association with at-risk drinking
      (defined as more than 14 drinks per week for males or 7 drinks per week for
      females) and intoxication. Most (81%) of the participants were male, 50% were
      Hispanic, and 36% African American. The average age of respondents was 40 years.
      Injection risk behaviors that were examined were distributive sharing of
      needles/syringes and distributive sharing of needles/syringes with multiple IDUs.
      Sexual risk behaviors included multiple sex partners, engaging in unprotected
      sex, and among women, engaging in trade sex. After adjusting for the effects of
      other variables, at-risk drinking among cocaine injectors was associated with
      distributive sharing of needles/syringes. At-risk drinkers were also more likely
      to engage in unprotected sex with a casual partner. Finally, among cocaine
      injectors alcohol intoxication during the most recent sex episode was associated
      with unprotected sex with a casual partner. These observations indicate that
      among HIV-positive IDUs at-risk drinking is associated with higher rates of
      injection and sexual risk behaviors and that alcohol intoxication is related to
      unprotected sex.

PMID- 19591611
TI  - Re: Computed tomography-determined stone-free rates for ureteroscopy of upper
      tract stones (from Macejko A, Okotie OT, Zhao LC, Liu J, Perry K, Nadler RB. J
      Endourol 2009;23:379-382).

PMID- 19591613
TI  - Robot-assisted laparoscopic bladder diverticulectomy combined with photoselective
      vaporization of prostate: a case report and review of literature.
AB  - PURPOSE: Open surgery, endoscopic technique, and standard laparoscopic technique
      are surgical options for the management of bladder diverticuli. In this article,
      we report robot-assisted bladder diverticulectomy (RABD) and photoselective
      vaporization of prostate (PVP) in the same patient sequentially. To the best of
      our knowledge, this is the first case report of RABD combined with PVP. MATERIALS
      AND METHODS: A 63-year-old patient with benign prostatic hyperplasia and a
      secondary large bladder diverticulum underwent sequential PVP and RABD.
      Cystoscopic examination revealed obstructing prostate lobes and a large
      diverticulum at posterior wall of bladder. After completion of PVP procedure, a
      16F urethral catheter was inserted into the diverticulum via outer sheath of
      optic urethrotome and another 16F urethral catheter was left in bladder for
      urinary drainage. A transperitoneal approach was preferred. The diverticulum was
      distended with saline infusion via the Foley catheter inside the diverticulum.
      The distended diverticulum was seen easily and dissected from the surrounding
      tissue. The bladder was closed in two separate layers. RESULTS: Total operative
      time, including diverticulectomy with PVP procedure, was 230 minutes, and console
      time was 90 minutes. The length of stay was 7 days. CONCLUSIONS: There has been
      always concern about the high intravesical pressures secondary to irrigant
      instillation that may disrupt the bladder repair. To avoid this problem we
      combined robotic diverticulectomy with PVP. Because of hemostatic properties of
      potassium-titanyl-phosphate laser, we did not encounter with bleeding after
      prostatectomy procedure. Moreover, we did not use irrigation, and the suture line
      of the bladder was kept safe. Therefore, we recommend to use greenlight laser in
      combined prostate and RABD operations. RABD is a feasible and safe procedure.
      RABD and PVP can be performed safely in the same patient sequentially.

PMID- 19591614
TI  - On the biomechanics of vaginal birth and common sequelae.
AB  - Approximately 11% of U.S. women undergo surgery for pelvic floor dysfunction,
      including genital organ prolapse and urinary and fecal incontinence. The major
      risk factor for developing these conditions is giving vaginal birth. Vaginal
      birth is a remarkable event about which little is known from a biomechanical
      perspective. We first review the functional anatomy of the female pelvic floor,
      the normal loads acting on the pelvic floor in activities of daily living, and
      the functional capacity of the pelvic floor muscles. Computer models show that
      the stretch ratio in the pelvic floor muscles can reach an extraordinary 3.26 by
      the end of the second stage of labor. Magnetic resonance images provide evidence
      that show that the pelvic floor regions experiencing the most stretch are at the
      greatest risk for injury, especially in forceps deliveries. A conceptual model
      suggests how these injuries may lead to the most common form of pelvic organ
      prolapse, a cystocele.

PMID- 19591615
TI  - Thirty-day mortality after transurethral resection of the prostate in patients
      treated with androgen deprivation therapy.
AB  - BACKGROUND AND PURPOSE: Seven percent of patients with prostate cancer (PCa) who
      are exposed to androgen deprivation therapy (ADT) may need transurethral
      resection of the prostate (TURP). Our objective was to examine the rate and the
      predictors of 30-day mortality (30dM) after TURP in patients who were exposed to
      ADT in a large, contemporary Canadian cohort. PATIENTS AND METHODS: We assessed
      the 30dM rate after TURP in 853 men with the diagnosis of PCa who were treated
      with primary ADT or radiation therapy followed by ADT. The effect of age,
      comorbidity (coded according to the Charlson Comorbidity Index [CCI]), number of
      previous TURP procedures, history of radiation therapy, exposure to
      antiandrogens, and the type and the duration of ADT before TURP were all tested
      in univariable and multivariable logistic regression models that predicted 30dM
      after TURP. RESULTS: During the initial 30 days after TURP, 38 deaths occurred
      (4.5%, 95% confidence interval: 3.2%-6.2%). Of all variables, the CCI was the
      only statistically significant (P = 0.001) predictor of 30dM after TURP. The
      accuracy of CCI in predicting 30dM after TURP in individual patients was 65.1%.
      Lack of consideration of clinical variables that could predict the 30dM rate
      after TURP, such as prostate size or prostate-specific antigen level, represents
      a limitation of this study. CONCLUSIONS: A substantial risk of 30dM is associated
      with TURP that is performed in patients who are exposed to ADT. Unfortunately,
      the predictors used in this analysis could not define the individual risk of 30dM
      with sufficient accuracy. Nonetheless, the average 4.5% risk should be considered
      at the time of informed consent.

PMID- 19591616
TI  - Transurethral resection of intravesical mesh after midurethral sling procedures.
AB  - PURPOSE: We evaluated the efficacy of the transurethral resection (TUR) for the
      management of intravesically exposed polypropylene mesh after midurethral sling
      (MUS) procedures. PATIENTS AND METHODS: Fourteen patients had a TUR for
      intravesical mesh after MUS procedures (tension-free vaginal tape, 11;
      transobturator tape, 3). In six patients with large stones, cystoscopic division
      and cystolitholapaxy were needed before the TUR. RESULTS: Patients presented with
      dysuria (9), hematuria (7), urgency incontinence (5), urinary frequency (2), and
      pelvic pain (2). Thirteen of 14 (92.9%) patients had the mesh completely removed
      during a mean follow-up of 18 months; one patient had a recurrent bladder stone.
      Complications included de novo mixed incontinence, pelvic hematoma, and
      vesicovaginal fistula among three patients. CONCLUSION: Urologists should suspect
      intravesical mesh erosion or stone formation in patients with persistent pain,
      hematuria, or bladder irritation symptoms after MUS procedures. The TUR was a
      useful treatment modality for patients with intravesical complications after MUS
      procedures.

PMID- 19591617
TI  - Spanish "fine tuning" of language to describe depression and anxiety.
AB  - On screening tools for emotional distress, the terms "depression" and "anxiety"
      are commonly used for patients with advanced cancer. However, these terms could
      have negative connotations in Spanish such that cultural and unexpected
      differences in perception may invalidate or skew the results of the screening if
      the best terms are not chosen. The goal of this study was to determine the best
      expression that can be used to explore anxiety and depression in Spanish. A
      prospective study of 100 Spanish-speaking patients was performed. Spanish
      patients with cancer completed the Hospital Anxiety and Depression Scale (HADS)
      and six Verbal Numerical Scales (VNS) exploring the level of anxiety using the
      terms ansioso (anxious), nervioso (nervous), or intranquilo (uneasy/disquiet),
      and the level of depression using the terms deprimido (depressed), desanimado
      (discouraged), or triste (sad). The correlation, sensitivity, and specificity for
      all the VNS and HADS (8 and 11 cutoff points) were analyzed. The correlation
      (Spearman rho) between HADS and the anxiety VNS was r = 0.557 using "anxious"; r
      = 0.603 using "nervous"; and r = 0.594 using "uneasy." The correlation for the
      depression VNS was r = 0.662 using "depression"; r = 0.759 using "discouraged"
      and r = 0.596 using "sad"; alpha < 0.001 was used in all VNS. A cutoff point of 4
      of 10 for any term used to explore anxiety achieved the best levels for
      sensitivity (0.80) and specificity (0.70). The term "discouraged" with a cutoff
      point of 4 of 10 shows a sensitivity of 0.89, a specificity of 0.84, as well as a
      predictive positive value of 0.77 and a negative value of 0.93. In Spanish, the
      term desanimado seems to be more suitable in screening for depression. Alternate
      terms could be used to explore anxiety in Spanish. Exploring depression with
      simple questions in Spanish achieves greater accuracy than the same approach to
      exploring anxiety.

PMID- 19591618
TI  - Index of problematic online experiences: item characteristics and correlation
      with negative symptomatology.
AB  - This exploratory study aimed to develop and test a quick, easily administered
      instrument, the Index of Problematic Online Experiences (I-POE). The goal of the
      I-POE extends beyond assessing for Internet overuse to broadly assess problematic
      Internet use across several domains and activities. Data was collected from 563
      college students from a Northern New England university using an online survey
      methodology. Results indicated the I-POE has adequate construct validity and is
      highly correlated with a variety of relevant constructs: depression,
      anger/irritability, tension-reduction behavior, sexual concerns, and
      dysfunctional sexual behavior as measured by the Trauma Symptom Inventory; as
      well as amount of Internet use and permissive attitudes toward engaging in a
      variety of sexual activities. Early flagging of online experiences could mitigate
      the negative effects associated with problematic use. The I-POE, as an easy-to
      administer, short screening index, holds promise in this regard. Initial testing
      of the instrument points to its utility in identifying persons who are
      experiencing a broad range of Internet-related problems.

PMID- 19591619
TI  - An assessment of prospective memory retrieval in women with chronic fatigue
      syndrome using a virtual-reality environment: an initial study.
AB  - People with chronic fatigue syndrome (CFS) have increased rates of depression,
      anxiety, and illness intrusiveness; they may also suffer from cognitive problems
      such as retrospective memory (RM) deficits and concentration difficulties that
      can stem from diminished information-processing capability. We predicted that
      this diminished capacity may also lead to deficits in other cognitive functions,
      such as prospective memory (ProM). Event-, time-, and activity-based ProM was
      assessed in 11 women with CFS and 12 healthy women using a computer-generated
      virtual environment (VE). RM was assessed using a free-recall test, and
      subjective assessment of both ProM and RM was assessed by questionnaire. Groups
      were equivalent in age and measures of IQ. People with CFS performed slightly
      worse than healthy controls on both the event- and time-based ProM measures,
      although these were not statistically significant. However, the CFS group
      performed significantly worse than the healthy controls on both the free recall
      task and on subjective assessment of both RM and ProM. Women with CFS do have
      some subtle decrements in memory, particularly RM. However, it is possible that
      the decrements found in the present sample would be greater in real life. Further
      studies utilizing both healthy controls and illness controls are now needed to
      ascertain how sensitive the VE measure is and to inform the development of tasks
      in the VE that place progressively increasing demands on working memory capacity.

PMID- 19591621
TI  - Laparoendoscopic single-site surgery of the kidney with no accessory trocars: an
      initial experience.
AB  - BACKGROUND AND PURPOSE: As laparoscopy becomes more commonplace for urologists,
      ongoing attempts are under way to minimize the number and size of incisions used
      for access. Laparoendoscopic single-site surgery (LESS) was developed and has
      been increasingly attempted as an extension of classic laparoscopy. Investigators
      hypothesize that LESS may offer a superior cosmetic result, faster recovery, and
      equivalent efficacy to laparoscopic surgery. Our aim is to present our experience
      with renal LESS. PATIENTS AND METHODS: A prospective data collection was
      performed on all patients who were undergoing renal LESS at our institution. A
      total of 11 renal LESS procedures were performed between July and November 2008:
      four LESS donor nephrectomies, two LESS radical nephrectomies, three LESS partial
      nephrectomies, and two LESS pyeloplasties. All LESS procedures replicated
      laparoscopic techniques but were performed through a single operative site using
      a 5-mm flexible-tip laparoscope and flexible working instruments. RESULTS: Six of
      the patients were men. The mean operative time was 162.4 +/- 38.5 minutes. The
      mean estimated blood loss was 104.5 +/- 41.6 mL, with a mean length of
      hospitalization of 2.4 +/- 0.8 days. There were no intraoperative complications
      or blood transfusions. Postoperative pain requirements were tabulated and
      revealed a mean in-hospital analgesic requirement of 44.8 +/- 46.7 mg (range 7
      158 mg) of morphine equivalents with three patients receiving intravenous
      ketorolac. CONCLUSION: Renal LESS is feasible as flexible laparoscopes and
      instruments continue to develop. In our initial experience, expert laparoscopic
      surgeons were able to perform these LESS procedures with equivalent efficacy
      without compromising perioperative measures, including operative time, blood
      loss, and hospital stay. Further prospective investigation through randomized
      studies is necessary to elucidate differences, if any, in postoperative analgesic
      requirements and patient satisfaction with postoperative cosmesis, and to confirm
      equivalent efficacy when compared with current standards.

PMID- 19591622
TI  - The application of endoscopic techniques in the management of upper tract
      recurrence after cystectomy and urinary diversion.
AB  - Although nephroureterectomy remains the gold-standard therapy for upper tract
      recurrence of transitional cell carcinoma after cystectomy and urinary diversion,
      conservative endoscopic techniques are increasingly being utilized for
      surveillance and management of recurrent low-grade upper tract lesions. A
      retrograde or antegrade approach is technically feasible and can be an effective
      alternative in patients with significant medical comorbidities, chronic renal
      insufficiency, bilateral disease, or solitary renal units. Recent series have
      expanded the utility of these procedures to include solitary, low-grade, and
      completely resectable tumors in patients with normal contralateral kidneys who
      are willing to accept lifelong surveillance for recurrence. With increasing
      experience and improvements in endoscopic equipment, the endourologic management
      of upper tract recurrence after cystectomy and lower urinary tract reconstruction
      is an appealing option in select patients. The difficulties with urinary tract
      access, preservation of renal function, and oncologic efficacy must all be taken
      into consideration in these complex patients. The aims of this report are to
      review the outcomes of contemporary series of upper tract recurrence of
      transitional cell carcinoma managed endoscopically, and to discuss the
      application of endourologic techniques in patients who have undergone cystectomy
      and lower urinary tract reconstruction.

PMID- 19591623
TI  - Bilateral simultaneous totally tubeless percutaneous nephrolithotomy: preliminary
      report of six cases.
AB  - PURPOSE: To evaluate the feasibility and safety of bilateral simultaneous
      tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: From August
      2007 to January 2008, six patients underwent bilateral simultaneous totally
      tubeless PCNL. Patients who needed more than one access, who had significant
      intraoperative bleeding, and who had pelvicaliceal system perforations or a
      residual stone were excluded from the study group. Preliminary results were
      analyzed in six patients. RESULTS: Five men and one woman patient with a mean age
      of 50.1 years underwent a bilateral totally tubeless procedure. The mean stone
      burden was 524.5 mm(2) (range 100 mm(2)-1800 mm(2)). The mean drop in hemoglobin
      was 1.55 g/dL (range 0.6-2.6 g/dL). No blood transfusion was necessary in any
      patient. The mean hospitalization time was 1.8 days (range 1-4 d). A
      complications was encountered in one patient; the patient had anuria
      postoperatively for 16 hours, which resolved after the insertion of bilateral
      Double-J stents. CONCLUSIONS: Bilateral simultaneous tubeless PCNL procedure
      should be kept in mind for selected patients. Prospective randomized studies with
      large series are necessary for further evaluation of the procedure.

PMID- 19591624
TI  - "South Dakota's Dying to Know": a statewide survey about end of life.
AB  - OBJECTIVE: To develop a baseline understanding of attitudes, advance planning,
      knowledge, and preferences about end-of-life (EOL) care among community-dwelling
      South Dakotans. METHODS: Surveys were sent to 10,204 randomly selected households
      in South Dakota in August 2005, resulting in a 24.8% return rate (N = 2533). Data
      were entered into the computer for subsequent univariate (frequencies) and
      bivariate (using chi(2)) analysis. RESULTS: Most respondents said preparation for
      EOL was very important, yet far fewer had actually taken steps to ensure their
      EOL wishes would be known or honored. Most people did not want artificial
      hydration/nutrition at EOL, preferred to die at home, and harbored misconceptions
      about pain; yet, most had not engaged in conversations with their physician,
      minister, or lawyer about these issues. While some adults were unfamiliar with
      hospice care, when provided with a definition, a majority indicated that they
      would want hospice care if they were dying and preferably in their own homes.
      CONCLUSION: Disparities between what South Dakotans want at EOL and what actions
      they have taken to address those preferences challenge individuals, families, and
      professionals to engage in conversation to redress this inconsistency.
      Receptivity to physician-initiated EOL conversations suggests this talk be
      included with all patients, not just those who are elderly or at EOL. Data from
      this statewide study of community-dwelling adults provide information to better
      understand EOL preferences and to inform health policy and practice.

PMID- 19591625
TI  - Is a home-care network necessary to access the Medicare hospice benefit?
AB  - OBJECTIVE: To test whether the presence of an informal or formal care network in
      the home leads to different hospice utilization patterns near death. To examine
      how the informal care relationship affects hospice use patterns. DATA SOURCES:
      Medicare Current Beneficiary Survey (MCBS), 1997-2001. STUDY DESIGN: Using
      logistic regression and ordinary least squares, we examine the association
      between a person's in-home network of care and the use of Medicare hospice
      services in the last year of life. We also examine whether the care-dyad
      relationship is associated with different hospice use patterns. DATA EXTRACTION:
      All individuals in the MCBS who lived at home at the time of the interview and
      who died between 1998 and 2001, 1404 persons. PRINCIPAL FINDINGS: People
      receiving formal home care had a much higher chance of enrolling in hospice prior
      to death. Informal care did not influence the likelihood of hospice but was
      associated with longer use among hospice users. Daughter caregivers increased the
      likelihood and duration of hospice use whereas sons significantly decreased the
      likelihood. CONCLUSIONS: Because formal care is associated with increased use of
      hospice, future work should examine whether patients without an in-home network
      faced access barriers. Caregiver relationships had large effects on length of
      hospice stays, yet we do not know whether changes moved a patient closer to or
      further away from their optimum use of the benefit.

PMID- 19591626
TI  - Development and progress of engineering of skeletal muscle tissue.
AB  - Engineering skeletal muscle tissue remains still a challenge, and numerous
      studies have indicated that this technique may be of great importance in medicine
      in the near future. This article reviews some of the recent findings resulting
      from tissue engineering science related to the contractile behavior and the
      phenotypes of muscle tissue cells in different three-dimensional environment, and
      discusses how tissue engineering could be used to create and regenerate skeletal
      muscle, as well as the extended applications and the related patents concerned
      with engineered skeletal muscle.

PMID- 19591627
TI  - Overview of biologic therapy for Crohn's disease.
AB  - Therapy for Crohn's disease (CD) is evolving at breakneck speed. Biologic
      therapies are assuming ever more important roles in treating this unrelenting,
      life-long disorder. New evidence suggests that earlier, more aggressive use of
      biological therapies for CD may improve overall efficacy rates, as well as reduce
      long-term complications. In addition to optimizing the use of older biologic
      therapies (antibodies against TNF-alpha), recent and ongoing clinical trials are
      evaluating the clinical efficacy of a large number of other biologic therapies,
      honing in on a wide array of immunological targets. The promise of biologic
      therapies stems from their ability to induce complete and long-lasting remission
      of symptoms in a way that 'standard' therapies have not been able to accomplish.
      In this review of biologic therapies for CD, we examine the latest clinical trial
      data and evidence for mechanism of action of a variety of current and future
      therapies.

PMID- 19591628
TI  - Structural biology of carbohydrate xenoantigens.
AB  - Transplantation of organs across species (xenotransplantation) is being
      considered to overcome the shortage of human donor organs. However, unmodified
      pig organs undergo an antibody-mediated hyperacute rejection that is brought
      about by the presence of natural antibodies to Galalpha(1,3)Gal, which is the
      major carbohydrate xenoantigen. Genetic modification of pig organs to remove most
      of the Galalpha(1,3)Gal epitopes has been achieved, but the human immune system
      may still recognize residual lipid-linked Galalpha(1,3)Gal carbohydrates, new
      (cryptic) carbohydrates or additional non-Galalpha(1,3)Gal carbohydrate
      xenoantigens. The structural basis for lectin and antibody recognition of
      Galalpha(1,3)Gal carbohydrates is starting to be understood and is discussed in
      this review. Antibody binding to Galalpha(1,3)Gal carbohydrates is predicted to
      primarily involve end-on insertion of the terminal alphaGal residue, but it is
      possible that groove-type binding can occur, as for some lectins. It is likely
      that similar antibody and lectin recognition will occur with other non
      Galalpha(1,3)Gal xenoantigens, which potentially represent new barriers for pig
      to-human xenotransplantation.

PMID- 19591629
TI  - Multipeptide vaccination in cancer patients.
AB  - Since the identification of tumor associated antigens (TAA) in different tumor
      histotypes, many vaccination strategies have been investigated, including peptide
      based vaccines. Results from the first decade of clinical experimentation, though
      demonstrating the feasibility and the good toxicity profile of this approach,
      provided evidence of clinical activity only in a minority of patients, despite
      inducing immunization in up to 50% of them. In this review, we discuss the
      different approaches recently developed in order to induce stronger peptide
      induced immune-mediated tumor growth control, possibly translating into improved
      clinical response rates, with specific focus on multipeptide-based anti-cancer
      vaccines. This strategy offers many advantages, such as the possibility of
      bypassing tumor heterogeneity and selection of antigen (Ag)-negative clones
      escaping peptide-specific immune responses, or combining HLA class I- and class
      II-restricted epitopes, thus eliciting both CD4- and CD8-mediated immune
      recognition. Notably, advances in Ag discovery technologies permit further
      optimization of peptide selection, in terms of identification of tumor-specific
      and unique TAA as well as Ags derived from different tumor microenvironment cell
      components. With the ultimate goal of combining peptide selection with patient
      specific immunogenic profile, peptide based anti-cancer vaccines remain a
      promising treatment for cancer patients, as attested by of pre-clinical and
      clinical studies.

PMID- 19591630
TI  - A critical review on a globally-licensed, live, orally-administrable, monovalent
      human rotavirus vaccine: Rotarix.
AB  - Rotavirus is the major cause of severe gastroenteritis in children worldwide, and
      two, live, orally-administrable vaccines are licensed globally. They are Rotarix,
      a monovalent, human rotavirus-based vaccine (GlaxoSmithKline), and RotaTeq, a
      pentavalent, bovine-human reassortant vaccine (Merck). The RIX4414 strain, a
      G1P[8] virus, is contained in the Rotarix vaccine. It grows efficiently in the
      human intestine, as evidenced by vaccine virus shedding into faeces. Efficient
      multiplication of RIX4414 in the intestines may play a role in stimulating immune
      effectors other than neutralizing antibodies that may explain the protective
      immunity against fully heterotypic G2P[4] strains. The protective efficacy
      against severe rotavirus gastroenteritis afforded by Rotarix is consistently
      better against strains that share with RIX4414 both G and P serotypes (i.e.,
      G1P[8]), or only P serotype (i.e., G3P[8], G4P[8] and G9P[8]). The Rotarix
      vaccine is safe regarding intussusception if its first dose is administered
      between 6 and 12 weeks of age and the last dose by 24 weeks of age with a minimum
      interval of 4 weeks between the two doses. The expansion by Advisory Committee on
      Immunization Practices, USA, of the age limit for the first dose to age <15
      weeks, and the last dose by 8 months requires close monitoring.

PMID- 19591633
TI  - Imaging of gout: findings and utility.
AB  - Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic
      joint inflammation. Chronic gout is associated with changes in joint structures
      that may be evaluated with diverse imaging techniques. Plain radiographs show
      typical changes only in advanced chronic gout. Computed tomography may best
      evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate
      soft tissues, synovial membrane thickness, and inflammatory changes.
      Ultrasonography is a tool that may be used in the clinical setting, allowing
      evaluation of cartilage, soft tissues, urate crystal deposition, and synovial
      membrane inflammation. Also ultrasound-guided puncture may be useful for
      obtaining samples for crystal observation. Any of these techniques deserve some
      consideration for feasibility and implementation both in clinical practice and as
      outcome measures for clinical trials. In clinical practice they may be considered
      mainly for evaluating the presence and extent of crystal deposition, and
      structural changes that may impair function or functional outcomes, and also to
      monitor the response to urate-lowering therapy.

PMID- 19591634
TI  - AIT test has no problem in the detection of anti-ribosomal P.

PMID- 19591635
TI  - The quest for a biomarker of circulating osteoclast precursors.
AB  - Osteoclast precursors arise from the CD14+ CD16- population in controls but
      details about cell surface marker expression and functional characteristics of
      these cells is unknown, particularly in patients with inflammatory arthritis. In
      a recent issue of Arthritis, Research and Therapy, Lari and colleagues found that
      osteoclasts developed from a proliferative CD14+ CD16- subset in healthy
      controls. These cells took on the morphology of osteoclasts, expressed mRNA for
      osteoclast-related genes and excavated pits on bone wafers. These findings
      provide new insights into monocyte diversity and provide evidence that osteoclast
      precursors arise from a small proliferating monocyte population in controls.
      Additional studies are needed in patients with inflammatory arthritis.

PMID- 19591631
TI  - The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients.
AB  - Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor
      cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor
      specific mutations may allow for more precise eradication of neoplastic cells.
      EGFR variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed
      in GBM and other neoplasms and its expression enhances tumorigenicity. This in
      frame deletion mutation splits a codon, resulting in a novel glycine at the
      fusion junction producing a tumor-specific epitope target for cellular or humoral
      immunotherapy. We have previously shown that vaccination with a peptide that
      spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious
      immunotherapy in syngeneic murine models. In this review, we summarize our
      results in GBM patients targeting this mutation in multiple, multi-institutional
      Phase II immunotherapy trials. These trials demonstrated that a selected
      population of GBM patients who received vaccines targeting EGFRvIII had an
      unexpectedly long survival time. Further therapeutic strategies and potential
      pitfalls of using this approach are discussed.

PMID- 19591636
TI  - Stress of different types increases the proinflammatory load in rheumatoid
      arthritis.
AB  - Stress in patients with chronic inflammatory diseases such as rheumatoid
      arthritis (RA) stimulates proinflammatory mechanisms due to the defect of stress
      response systems (for example, the sympathetic nervous system and the
      hypothalamic-pituitary-adrenal axis). Among other mechanisms, the loss of
      sympathetic nerve fibers in inflamed tissue and inadequate cortisol secretion in
      relation to inflammation lead to an enhanced proinflammatory load in RA. Stress
      and the subsequent stimulation of inflammation (systemic and local) lead to
      increased sensitization of pain and further defects of stress response systems
      (vicious cycle of stress, pain, and inflammation).

PMID- 19591638
TI  - Predicting the future of anti-tumor necrosis factor therapy.
AB  - Tumor necrosis factor (TNF) antagonists are approved worldwide for the treatment
      of rheumatoid arthritis (RA). Clinical experience revealed that TNF-blocking
      therapy is effective for only approximately two thirds of patients, reflecting
      that there are 'responders' as well as 'nonresponders'. Given the destructive
      nature of RA, the risk of adverse effects, and considerable costs for therapy,
      there is a strong need to make predictions on success before the start of
      therapy. In the current issue of Arthritis Research & Therapy, Hueber and
      colleagues become the first to present a multi-parameter serum protein biomarker
      set that has predictive value prior to the start of anti-TNF treatment.
      Ultimately, this finding may contribute to a personalized form of medicine,
      whereby a specific therapy will be applied that is best suited to an individual
      patient.

PMID- 19591637
TI  - Progress in spondylarthritis. Immunopathogenesis of spondyloarthritis: which
      cells drive disease?
AB  - Spondyloarthritides, or SpA, form a cluster of chronic inflammatory diseases with
      the axial skeleton as the most typical disease localisation, although extra
      articular manifestations such as intestinal inflammation may frequently occur
      during the course of the disease. This review summarises recent progress in our
      understanding of the immunopathogenesis of SpA with special emphasis on the
      cellular constituents considered to be responsible for the initiation and/or
      perpetuation of inflammation. There are several arguments favouring a role for
      haematopoietic cells in the pathophysiology of spondyloarthritis, including HLA
      B27-associated dendritic cell disturbances, HLA-B27 misfolding properties and T
      helper 17 cells. In addition, recent studies have pointed toward a pivotal role
      for stromal cells. A major challenge, however, remains to determine how recently
      identified genetic associations such as interleukin-23 receptor polymorphisms may
      influence cellular targets in spondyloarthritis.

PMID- 19591639
TI  - Inhibitory short synthetic oligodeoxynucleotides and lupus.
AB  - B cells and antigen-presenting cells express a group of intracellular Toll-like
      receptors (TLRs) that recognize nucleic acids and can be accessed only when
      apoptotic debris or immune complexes are internalized by B-cell receptors or Fc
      receptors. This results in rapid cell activation and release of inflammatory
      mediators that perpetuate the autoantibody response. TLR-7 and TLR-9 are required
      to generate autoantibodies to RNA and DNA, respectively. Synthetic
      oligodeoxynucleotides that inhibit the activity of these intracellular TLRs
      attenuate systemic lupus erythematosus in mouse models and may be of therapeutic
      benefit in human systemic lupus erythematosus.

PMID- 19591640
TI  - ICU admission and severity assessment in community-acquired pneumonia.
AB  - The past 15 years have seen major advances in our understanding of severity
      assessment in community-acquired pneumonia (CAP). Prognostic tools have been
      promoted to guide all major management decisions in CAP, including admission to
      the critical care unit. Several recent studies, including the study by Renaud and
      colleagues, have challenged us to re-evaluate how we consider severe CAP, a
      concept for which there is still no universally accepted definition. Existing
      severity scores such as the Pneumonia Severity Index and the CURB65 score are
      designed to predict 30-day mortality. As a result, they are heavily weighted by
      age and co-morbidity. They perform less well when predicting other outcomes such
      as requirement for ICU admission and are of limited use in the critical care
      environment. This commentary discusses recent attempts to develop useful severity
      criteria to guide the use of ICU resources in patients with severe CAP.

PMID- 19591641
TI  - Recently published papers: changing bandwagons, innovations and questioning
      dogma.
AB  - This issue's Recently published papers commentary considers the popular and muddy
      waters of glycaemic control, stops briefly to ponder the incidence of pulmonary
      embolus in acute exacerbations of chronic obstructive pulmonary disease, promotes
      novel studies in the areas of traumatic brain injury and extracorporeal circuits,
      and rounds off with a potentially dogma-challenging study in cardiac arrest.

PMID- 19591642
TI  - Latent viral infections in critically ill patients.

PMID- 19591643
TI  - NAC: still the way to go.

PMID- 19591644
TI  - Tackling agitated delirium--the tip of the iceberg.
AB  - Reade et al. studied 20 agitated intubated patients in a pilot open-label trial
      comparing the efficacy of dexmedetomidine versus haloperidol in facilitating
      extubation. While the study design had limitations, which are outlined by the
      authors themselves in the paper published in this issue of Critical Care, the
      study demonstrated an impressive reduction in time to extubation and length of
      stay. Dexmedetomidine is a promising sedative agent that acts via alpha2
      receptors and has been shown to decrease prevalence and duration of delirium in
      mechanically ventilated patients. Haloperidol is the recommended and standard
      drug to treat delirium, largely based on large case series and reports. Delirium
      is a common, underdiagnosed and serious problem in intensive care unit patients.
      Agitated delirious patients are at risk of immediate adverse events as well as
      prolonged respiratory support. All delirious patients are at risk of poor
      cognitive outcomes. Further research is needed into the pharmacological
      management of delirium, including the use of dexmedetomidine in the management of
      agitation and the clinical efficacy of haloperidol.

PMID- 19591645
TI  - What my genome told me--and what it didn't.
AB  - Lessons in personal genome analysis, social networking or health information?

PMID- 19591648
TI  - Interfacing systems biology and synthetic biology.
AB  - A report of BioSysBio 2009, the IET conference on Synthetic Biology, Systems
      Biology and Bioinformatics, Cambridge, UK, 23-25 March 2009.

PMID- 19591647
TI  - Genetics and genomics converge on the human blood fluke.
AB  - The construction of a genetic map of the human infective blood fluke (Schistosoma
      mansoni), coupled with the availability of the genome sequence, offers new
      approaches for research on this important parasitic worm.

PMID- 19591646
TI  - Translational disease interpretation with molecular networks.
AB  - Molecular networks are being used to reconcile genotypes and phenotypes by
      integrating medical information. In this context, networks will be instrumental
      for the interpretation of disease at the personalized medicine level.

PMID- 19591650
TI  - Clocks, cryptochromes and Monarch migrations.
AB  - The annual migration of the Monarch butterfly (Danaus plexippus) from eastern
      North America to central Mexico is one of nature's most inspiring spectacles.
      Recent studies including one in BMC Biology, have begun to dissect the molecular
      and neurogenetic basis for this most complex behavior.

PMID- 19591651
TI  - Do unicolonial wood ants favor kin?
AB  - Vast supercolonies of interconnected nests formed by unicolonial ant species are
      the largest cooperative groups of animals known. Research published recently in
      BMC Evolutionary Biology reveals that a supercolony can be more genetically
      structured than previously thought, comprising several extended families.
      Surprisingly, the families coexist peacefully, even though they seem to recognize
      each other as non-kin.

PMID- 19591649
TI  - A passport to neurotransmitter identity.
AB  - Comparison of a regulatory network that specifies dopaminergic neurons in
      Caenorhabditis elegans to the development of vertebrate dopamine systems in the
      mouse reveals a possible partial conservation of such a network.

PMID- 19591652
TI  - Vernalization in cereals.
AB  - How vernalization - exposure to a period of cold - induces flowering in
      Arabidopsis has been intensively investigated at the genetic and moleular levels.
      Recent papers, including one in BMC Plant Biology, shed light on changes in gene
      regulation that occur on vernalization in cereals.

PMID- 19591653
TI  - Molecular therapies for systemic lupus erythematosus: clinical trials and future
      prospects.
AB  - The prognosis of patients with systemic lupus erythematosus has greatly improved
      since treatment regimens combining corticosteroids and immunosuppressive
      medications have been widely adopted in therapeutic strategies given to these
      patients. Immune suppression is evidently efficient but also leads to higher
      susceptibility to infectious and malignant diseases. Toxic effects and sometimes
      unexpectedly dramatic complications of current therapies have been progressively
      reported. Identifying novel molecular targets therefore remains an important
      issue in the treatment of lupus. The aim of this review article is to highlight
      emerging pharmacological options and new therapeutic avenues for lupus with a
      particular focus on non-antibody molecular strategies.

PMID- 19591654
TI  - Epidemiology, costs, and the economic burden of fibromyalgia.
AB  - The assumption that fibromyalgia is associated with a major impact on the
      utilization of both healthcare and nonhealthcare resources has not been
      thoroughly supported by evidence-based data. Despite the differences between
      healthcare and sociopolitical systems in various countries, more recent results
      from epidemiological research now clearly demonstrate the socioeconomic burden of
      fibromyalgia and its comorbidities. The costs of the disease, calculated in
      single studies and countries, allow estimates for populations in other countries.
      The alarming results highlight the urgent need both for more research (including
      pathophysiology and epidemiology) and for the acceptance of emerging treatment
      challenges.

PMID- 19591656
TI  - Ultrasound has the potential to detect degeneration of articular   cartilage
      clinically, even if the information is obtained from an   indirect measurement of
      intrinsic physical characteristics.

PMID- 19591657
TI  - Serum levels of hyaluronic acid and chondroitin sulfate as a non-invasive method
      to evaluate healing after cartilage repair procedures.
AB  - Magnetic resonance imaging remains the only non-invasive method to assess the
      quality of cartilage repair procedures, but ideally would be complemented by
      other modalities, particularly blood tests. Nganvongpanit and colleagues
      investigated serum levels of hyaluronic acid (HA) and chondroitin sulfate (CS)
      for their correlation with tissue quality after cartilage repair with autologous
      chondrocytes versus subchondral drilling in a dog model. They reported better
      tissue quality in animals treated with chondrocyte implantation. Serum levels
      correlated with the histological score of biopsy samples: CS showed a negative (r
      = -0.69) and HA a positive (r = +0.46) correlation. Many questions remain to be
      answered before serum markers can provide a reliable, non-invasive tool to assess
      tissue quality, but these data provide an important foundation for additional
      research.

PMID- 19591655
TI  - Pathogenesis of tendinopathies: inflammation or degeneration?
AB  - The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and
      whether inflammation or degeneration has the prominent role is still a matter of
      debate. Assuming that there is a continuum from physiology to pathology, overuse
      may be considered as the initial disease factor; in this context, microruptures
      of tendon fibers occur and several molecules are expressed, some of which promote
      the healing process, while others, including inflammatory cytokines, act as
      disease mediators. Neural in-growth that accompanies the neovessels explains the
      occurrence of pain and triggers neurogenic-mediated inflammation. It is
      conceivable that inflammation and degeneration are not mutually exclusive, but
      work together in the pathogenesis of tendinopathies.

PMID- 19591658
TI  - Validation of continuous cardiac output technologies: consensus still awaited.
AB  - An ability to measure cardiac output in a continuous and non-invasive fashion is
      eagerly awaited in the field of intensive care practice. Modern technologies
      purport to be able to do this, but the design of studies that validate the
      manufacturers' claims is by no means straightforward. It is imperative that the
      scientific community describes and agrees on a set of principles that will enable
      us to design and then review and assess future validation studies, so that new
      technologies can be fairly assessed and compared with their competitors.

PMID- 19591659
TI  - Incretins in the ICU: is insulin on its way out?
AB  - Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that
      stimulate insulin secretion and suppress glucagon secretion, thus playing a key
      role in glucose homeostasis. While incretin mimetics and enhancers are approved
      for treatment of outpatients with diabetes, evidence is only starting to
      accumulate regarding the therapeutic potential of incretins in hospitalized
      patients. Small exploratory studies suggest that GLP-1 safely reduces
      hyperglycemia without causing hypoglycemia, a key advantage over insulin if
      efficacy is established in larger studies. Potential limitations include the need
      for a continuous infusion for delivery, attenuation but not normalization of
      glucose levels, increased deceleration of gastric emptying and nausea. The exact
      mechanism of action, dosing, adverse effects, patient subgroups that would be
      most suitable and safety of combination treatment with insulin remain to be
      studied. While promising, additional research is required studying effects on
      hard clinical endpoints.

PMID- 19591660
TI  - Broadening our perspectives on ICU delirium risk factors.
AB  - ICU delirium is associated with poor patient outcome. Risk factor stratification
      is essential to the understanding, prevention and treatment of this disorder.
      Alcohol consumption, smoking and prior cognitive impairment appear strongly
      correlated with delirium risk. Several potentially modifiable associations
      deserve prospective study: these include administration of sedatives and opiates;
      multiple catheters; as well as minimizing physical restraints and enabling
      visitors.

PMID- 19591661
TI  - Floral induction and monocarpic versus polycarpic life histories.
AB  - Recent work in Arabis alpina, a perennial relative of Arabidopsis, has uncovered
      subtle differences in control of a gene that represses flowering which
      contributes to the polycarpic habit.

PMID- 19591662
TI  - A Candida-based view of fungal sex and pathogenesis.
AB  - Analysis of the genomes of multiple Candida species reveals shared traits
      associated with pathogenesis, but also striking differences in sexual
      reproduction.

PMID- 19591663
TI  - Exploring the unknown: assumptions about allelic architecture and strategies for
      susceptibility variant discovery.
AB  - Identification of common-variant associations for many common disorders has been
      highly effective, but the loci detected so far typically explain only a small
      proportion of the genetic predisposition to disease. Extending explained genetic
      variance is one of the major near-term goals of human genetic research. Next
      generation sequencing technologies offer great promise, but optimal strategies
      for their deployment remain uncertain, not least because we lack a clear view of
      the characteristics of the variants being sought. Here, I discuss what can and
      cannot be inferred about complex trait disease architecture from the information
      currently available and review the implications for future research strategies.

PMID- 19591664
TI  - The 2009 European Society of Human Genetics Meeting: novel technologies driving
      change.
AB  - A report on the meeting of the European Society of Human Genetics, Vienna,
      Austria, 23-26 May 2009.

PMID- 19591665
TI  - Oncoproteomic profiling with antibody microarrays.
AB  - The incidence of cancer and its associated mortality are increasing globally,
      indicating an urgent need to develop even more effective and sensitive sets of
      biomarkers that could help in early diagnosis and consequent intervention. Given
      that many cellular processes are carried out by proteins, cancer research has
      recently shifted toward an exploration of the full proteome for such discovery.
      Among the advanced methodologies that are being developed for analyzing the
      proteome, antibody microarrays have become a prominent tool for gathering the
      information required for a better understanding of disease biology, early
      detection, discrimination of tumors and monitoring of disease progression. Here,
      we review the technical aspects and challenges in the development and use of
      antibody microarray assays and examine recently reported applications in
      oncoproteomics.

PMID- 19591666
TI  - A comparison of random forest and its Gini importance with standard chemometric
      methods for the feature selection and classification of spectral data.
AB  - BACKGROUND: Regularized regression methods such as principal component or partial
      least squares regression perform well in learning tasks on high dimensional
      spectral data, but cannot explicitly eliminate irrelevant features. The random
      forest classifier with its associated Gini feature importance, on the other hand,
      allows for an explicit feature elimination, but may not be optimally adapted to
      spectral data due to the topology of its constituent classification trees which
      are based on orthogonal splits in feature space. RESULTS: We propose to combine
      the best of both approaches, and evaluated the joint use of a feature selection
      based on a recursive feature elimination using the Gini importance of random
      forests' together with regularized classification methods on spectral data sets
      from medical diagnostics, chemotaxonomy, biomedical analytics, food science, and
      synthetically modified spectral data. Here, a feature selection using the Gini
      feature importance with a regularized classification by discriminant partial
      least squares regression performed as well as or better than a filtering
      according to different univariate statistical tests, or using regression
      coefficients in a backward feature elimination. It outperformed the direct
      application of the random forest classifier, or the direct application of the
      regularized classifiers on the full set of features. CONCLUSION: The Gini
      importance of the random forest provided superior means for measuring feature
      relevance on spectral data, but - on an optimal subset of features - the
      regularized classifiers might be preferable over the random forest classifier, in
      spite of their limitation to model linear dependencies only. A feature selection
      based on Gini importance, however, may precede a regularized linear
      classification to identify this optimal subset of features, and to earn a double
      benefit of both dimensionality reduction and the elimination of noise from the
      classification task.

PMID- 19591667
TI  - Profiling microRNA expression in Arabidopsis pollen using microRNA array and real
      time PCR.
AB  - BACKGROUND: MicroRNAs (miRNAs) are approximately 22-nt small non-coding RNAs that
      regulate the expression of specific target genes in many eukaryotes. In higher
      plants, miRNAs are involved in developmental processes and stress responses.
      Sexual reproduction in flowering plants relies on pollen, the male gametophyte,
      to deliver sperm cells to fertilize the egg cell hidden in the embryo sac.
      Studies indicated that post-transcriptional processes are important for
      regulating gene expression during pollen function. However, we still have very
      limited knowledge on the involved gene regulatory mechanisms. Especially, the
      function of miRNAs in pollen remains unknown. RESULTS: Using miRCURY LNA array
      technology, we have profiled the expression of 70 known miRNAs (representing 121
      miRBase IDs) in Arabidopsis mature pollen, and compared the expression of these
      miRNAs in pollen and young inflorescence. Thirty-seven probes on the array were
      identified using RNAs isolated from mature pollen, 26 of which showed significant
      differences in expression between mature pollen and inflorescence. Real-time PCR
      based on TaqMan miRNA assays confirmed the expression of 22 miRNAs in mature
      pollen, and identified 8 additional miRNAs that were expressed at low level in
      mature pollen. However, the expression of 11 miRNA that were identified on the
      array could not be confirmed by the Taqman miRNA assays. Analyses of
      transcriptome data for some miRNA target genes indicated that miRNAs are
      functional in pollen. CONCLUSION: In summary, our results showed that some known
      miRNAs were expressed in Arabidopsis mature pollen, with most of them being low
      abundant. The results can be utilized in future research to study post
      transcriptional gene regulation in pollen function.

PMID- 19591669
TI  - Geographical patterns in blood lead in relation to industrial emissions and
      traffic in Swedish children, 1978-2007.
AB  - BACKGROUND: Blood lead concentrations (B-Pb) were measured in 3 879 Swedish
      school children during the period 1978-2007. The objective was to study the
      effect of the proximity to lead sources based on the children's home and school
      location. METHODS: The children's home address and school location were geocoded
      and their proximity to a lead smelter and major roads was calculated using
      geographical information system (GIS) software. All the statistical analyses were
      carried out using means of generalized log-linear modelling, with natural
      logarithm-transformed B-Pb, adjusted for sex, school year, lead-exposing hobby,
      country of birth and, in the periods 1988-1994 and 1995-2007, parents' smoking
      habits. RESULTS: The GIS analysis revealed that although the emission from the
      smelter and children's B-Pb levels had decreased considerably since 1978,
      proximity to the lead smelter continued to affect levels of B-Pb, even in recent
      years (geometric mean: near smelter: 22.90 microg/l; far from smelter 19.75
      microg/l; p = 0.001). The analysis also revealed that proximity to major roads
      noticeably affected the children's B-Pb levels during the period 1978-1987
      (geometric mean near major roads: 44.26 microg/l; far from roads: 38.32 microg/l;
      p = 0.056), due to the considerable amount of lead in petrol. This effect was,
      however, not visible after 1987 due to prohibition of lead in petrol. CONCLUSION:
      The results show that proximity to the lead smelter still has an impact on the
      children's B-Pb levels. This is alarming since it could imply that living or
      working in the vicinity of a former lead source could pose a threat years after
      reduction of the emission. The analysis also revealed that urban children exposed
      to lead from traffic were only affected during the early period, when there were
      considerable amounts of lead in petrol, and that the prohibition of lead in
      petrol in later years led to reduced levels of lead in the blood of urban
      children.

PMID- 19591668
TI  - The potential biomarkers in predicting pathologic response of breast cancer to
      three different chemotherapy regimens: a case control study.
AB  - BACKGROUND: Preoperative chemotherapy (PCT) has become the standard of care in
      locally advanced breast cancer. The identification of patient-specific tumor
      characteristics that can improve the ability to predict response to therapy would
      help optimize treatment, improve treatment outcomes, and avoid unnecessary
      exposure to potential toxicities. This study is to determine whether selected
      biomarkers could predict pathologic response (PR) of breast tumors to three
      different PCT regimens, and to identify a subset of patients who would benefit
      from a given type of treatment. METHODS: 118 patients with primary breast tumor
      were identified and three PCT regimens including DEC
      (docetaxel+epirubicin+cyclophosphamide), VFC (vinorelbine/vincristine+5
      fluorouracil+cyclophosphamide) and EFC (epirubicin+5
      fluorouracil+cyclophosphamide) were investigated. Expression of steroid
      receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by
      immunohistochemical scoring on tumor tissues obtained before and after PCT. The
      PR of breast carcinoma was graded according to Sataloff's classification. Chi
      square test, logistic regression and Cochran-Mantel-Haenszel assay were performed
      to determine the association between biomarkers and PR, as well as the
      effectiveness of each regimen on induction of PR. RESULTS: There was a clear-cut
      correlation between the expression of ER and decreased PR to PCT in all three
      different regimens (p < 0.05). HER2 expression is significantly associated with
      increased PR in DEC regimen (p < 0.05), but not predictive for PR in EFC and VFC
      groups. No significant correlation was found between biomarkers PgR, Topo-II, P
      gp, MRP or GST-pi and PR to any tested PCT regimen. After adjusted by a
      stratification variable of ER or HER2, DEC regimen was more effective in inducing
      PR in comparison with VFC and EFC regimens. CONCLUSION: ER is an independent
      predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary
      breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR,
      Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens
      investigated. Results obtained in this clinical study may be helpful for the
      selection of appropriate treatments for breast cancer patients.

PMID- 19591671
TI  - Incidence and predictors of onboard injuries among Sri Lankan flight attendants.
AB  - BACKGROUND: Occupational injuries among flight attendants have not been given
      appropriate attention in Sri Lanka. The purpose of this study was to estimate the
      incidence of onboard injury among Sri Lankan flight attendants and to describe
      the determinants of onboard injury. METHODS: A descriptive cross-sectional study
      was carried out among Sri Lankan flight attendants. All flight attendants
      undergoing their annual health and first aid training were invited to
      participate. Flight attendants who flew continuously for a six-month period prior
      to data collection were included in the study sample. Recall history of injuries
      for a period of six months was recorded. RESULTS: The study sample consisted of
      98 (30.4%) male and 224 (69.6%) female flight attendants. The mean age of the
      study sample was 31 years (SD = 8) and the average duration of service was 10
      years (SD = 7). A total of 100 onboard falls, slips or trips in the previous six
      months were reported by 52 (16.1%) respondents. Of the total sample, 128 (39.8%)
      cabin crew members reported an injury in the six months preceding the study. This
      represents a total injury incidence of 795 per 1000 person per year. The leading
      causes of injury was pulling, pushing or lifting (60.2%). The commonest type of
      injuries were strains and sprains (52.3%). Turbulence related injuries were
      reported by 38 (29.7%) flight attendants. The upper limbs (44.5%) and the back
      (32%) were the commonest sites affected. After controlling for other factors,
      female flight attendants had 2.9 times higher risk (95% CI 1.2-7.2) of sustaining
      and injury than males. Irrespective of sex, body weight less than 56 kilograms
      (OR 2.9, 95% CI 1.4-5.8) and less than seven years of on board experience (OR
      10.5, 95% CI 3.6-31.0) were associated with higher risk of injury. CONCLUSION:
      Work related injury is a major occupational hazard to flight attendants.
      Appropriate preventive strategies are required to minimize them.

PMID- 19591670
TI  - A review of injury epidemiology in the UK and Europe: some methodological
      considerations in constructing rates.
AB  - BACKGROUND: Serious injuries have been stated as a public health priority in the
      UK. However, there appears to be a lack of information on population-based rates
      of serious injury (as defined by a recognised taxonomy of injury severity) at
      national level from either official statistics or research papers. We aim to
      address this through a search and review of literature primarily focused within
      the UK and Europe. METHODS: The review summarizes research papers on the subject
      of population based injury epidemiology published from 1970 to 2008. We examined
      critically methodological approaches in measuring injury incident rates including
      data sources, description of the injury pyramid, matching numerator and
      denominator populations as well as the relationship between injury and
      socioeconomic status. RESULTS: National representative rates come from research
      papers using official statistics sources, often focusing on mortality data alone.
      Few studies present data from the perspective of an injury pyramid or using a
      standardized measure of injury severity, i.e. Injury Severity Score (ISS). The
      population movement that may result in a possible numerator - denominator
      mismatch has been acknowledged in five research studies and in official
      statistics. The epidemiological profile shows over the past decades in UK and
      Europe a decrease in injury death rates. No major trauma population based rates
      are available within well defined populations across UK over recent time periods.
      Both fatal and non-fatal injury rates occurred more frequently in males than
      females with higher rates in males up to 65 years, then in females over 65 years.
      Road traffic crashes and falls are predominant injury mechanisms. Whereas a
      straightforward inverse association between injury death rates and socio-economic
      status has been observed, the evidence of socioeconomic inequalities in non-fatal
      injuries rates has not been wholly consistent. CONCLUSION: New methodological
      approaches should be developed to deal with the study design inconsistencies and
      the knowledge gaps identified across this review. Trauma registries contain
      injury data from hospitals within larger regions and code injury by Abbreviated
      Injury Scale enabling information on severity; these may be reliable data sources
      to improve understanding of injury epidemiology.

PMID- 19591672
TI  - Evaluation of a portable hemoglobin photometer in pregnant women in a high
      altitude area: a pilot study.
AB  - BACKGROUND: Anemia is a widespread public health problem associated with an
      increased risk of morbidity and mortality, especially in pregnant women. This
      study examined the agreement between a portable hemoglobin photometer and a
      laboratory analyzer in determining hemoglobin level in pregnant women. METHODS:
      This study recruited 69 pregnant women in Tibet, China. Capillary blood samples
      were taken to measure hemoglobin concentration using the hemoglobin photometer
      and the laboratory analyzer. Limit of agreement, concordance and intraclass
      correlation coefficient were used to evaluate the agreement. Laboratory
      measurement was considered as the standard reference method. Sensitivity and
      specificity were calculated to assess the error in screening for anemia. RESULTS:
      Mean difference between the two methods was -2.1 g/l. wide 95% limits of
      agreement were found (-22.6 g/l to 18.4 g/l). The intraclass correlation
      coefficient was 0.795, and concordance correlation coefficient was 0.793.
      Sensitivity and specificity were 94.9% and 76.7% respectively. Positive
      predictive value was 84.1%, and negative predictive value was 92.0%. CONCLUSION:
      This hemoglobin photometer is not recommended for determining hemoglobin
      concentration in pregnancy in a high altitude area.

PMID- 19591673
TI  - Diagnostic accuracy of spirometry in primary care.
AB  - BACKGROUND: To evaluate the sensitivity, specificity and predictive values of
      spirometry for the diagnosis of chronic obstructive pulmonary disease (COPD) and
      asthma in patients suspected of suffering from an obstructive airway disease
      (OAD) in primary care. METHODS: Cross sectional diagnostic study of 219 adult
      patients attending 10 general practices for the first time with complaints
      suspicious for OAD. All patients underwent spirometry and structured medical
      histories were documented. All patients received whole-body plethysmography (WBP)
      in a lung function laboratory. The reference standard was the Tiffeneau ratio
      (FEV1/VC) received by the spirometric maneuver during examination with WBP. In
      the event of inconclusive results, bronchial provocation was performed to
      determine bronchial hyper-responsiveness (BHR). Asthma was defined as a PC20 fall
      after inhaling methacholine concentration < or = 16 mg/ml. RESULTS: 90 (41.1%)
      patients suffered from asthma, 50 (22.8%) suffered from COPD, 79 (36.1%) had no
      OAD. The sensitivity for diagnosing airway obstruction in COPD was 92% (95%CI 80
      97); specificity was 84% (95%CI 77-89). The positive predictive value (PPV) was
      63% (95%CI 51-73); negative predictive value (NPV) was 97% (95%CI 93-99). The
      sensitivity for diagnosing airway obstruction in asthma was 29% (95%CI 21-39);
      specificity was 90% (95%CI 81-95). PPV was 77% (95%CI 60-88); NPV was 53% (95%CI
      45-61). CONCLUSION: COPD can be estimated with high diagnostic accuracy using
      spirometry. It is also possible to rule in asthma with spirometry. However,
      asthma can not be ruled out only using spirometry. This diagnostic uncertainty
      leads to an overestimation of asthma presence. Patients with inconclusive
      spirometric results should be referred for nitric oxide (NO) - measurement and/or
      bronchial provocation if possible to guarantee accurate diagnosis.

PMID- 19591674
TI  - Pulsed electromagnetic fields after arthroscopic treatment for osteochondral
      defects of the talus: double-blind randomized controlled multicenter trial.
AB  - BACKGROUND: Osteochondral talar defects usually affect athletic patients. The
      primary surgical treatment consists of arthroscopic debridement and
      microfracturing. Although this is mostly successful, early sport resumption is
      difficult to achieve, and it can take up to one year to obtain clinical
      improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar
      defects after arthroscopic treatment by promoting tissue healing, suppressing
      inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to
      sham-treatment after arthroscopy will lead to earlier resumption of sports, and
      aim at 25% increase in patients that resume sports. METHODS/DESIGN: A
      prospective, double-blind, randomized, placebo-controlled trial (RCT) will be
      conducted in five centers throughout the Netherlands and Belgium. 68 patients
      will be randomized to either active PEMF-treatment or sham-treatment for 60 days,
      four hours daily. They will be followed-up for one year. The combined primary
      outcome measures are (a) the percentage of patients that resume and maintain
      sports, and (b) the time to resumption of sports, defined by the Ankle Activity
      Score. Secondary outcome measures include resumption of work, subjective and
      objective scoring systems (American Orthopaedic Foot and Ankle Society--Ankle
      Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and
      satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports
      will be analyzed using Kaplan-Meier curves and log-rank tests. DISCUSSION: This
      trial will provide level-1 evidence on the effectiveness of PEMFs in the
      management of osteochondral ankle lesions after arthroscopy. TRIAL REGISTRATION:
      Netherlands Trial Register (NTR1636).

PMID- 19591675
TI  - Stable nuclear transformation of Gonium pectorale.
AB  - BACKGROUND: Green algae of the family Volvocaceae are a model lineage for
      studying the molecular evolution of multicellularity and cellular
      differentiation. The volvocine alga Gonium is intermediate in organizational
      complexity between its unicellular relative, Chlamydomonas, and its multicellular
      relatives with differentiated cell types, such as Volvox. Gonium pectorale
      consists of approximately 16 biflagellate cells arranged in a flat plate. The
      detailed molecular analysis of any species necessitates its accessibility to
      genetic manipulation, but, in volvocine algae, transformation procedures have so
      far only been established for Chlamydomonas reinhardtii and Volvox carteri.
      RESULTS: Stable nuclear transformation of G. pectorale was achieved using a
      heterologous dominant antibiotic resistance gene, the aminoglycoside 3'
      phosphotransferase VIII gene (aphVIII) of Streptomyces rimosus, as a selectable
      marker. Heterologous 3'- and 5'-untranslated flanking sequences, including
      promoters, were from Chlamydomonas reinhardtii or from Volvox carteri. After
      particle gun bombardment of wild type Gonium cells with plasmid-coated gold
      particles, transformants were recovered. The transformants were able to grow in
      the presence of the antibiotic paromomycin and produced a detectable level of the
      AphVIII protein. The plasmids integrated into the genome, and stable integration
      was verified after propagation for over 1400 colony generations. Co-transformants
      were recovered with a frequency of approximately 30-50% when cells were co
      bombarded with aphVIII-based selectable marker plasmids along with unselectable
      plasmids containing heterologous genes. The transcription of the co-transformed,
      unselectable genes was confirmed. After heterologous expression of the luciferase
      gene from the marine copepod Gaussia princeps, which was previously engineered to
      match the codon usage in C. reinhardtii, Gonium transformants show luciferase
      activity through light emission in bioluminescence assays. CONCLUSION: Flanking
      sequences that include promoters from C. reinhardtii and from V. carteri work in
      G. pectorale and allow the functional expression of heterologous genes, such as
      the selectable marker gene aphVIII of S. rimosus or the co-transformed, codon
      optimized G. princeps luciferase gene, which turned out to be a suitable reporter
      gene in Gonium. The availability of a method for transformation of Gonium makes
      genetic engineering of this species possible and allows for detailed studies in
      molecular evolution using the unicellular Chlamydomonas, the 16-celled Gonium,
      and the multicellular Volvox.

PMID- 19591677
TI  - Reliability and cross-cultural validity of a Japanese version of the Dental Fear
      Survey.
AB  - BACKGROUND: This study established the reliability and cross-cultural validity of
      a Japanese version of the Dental Fear Survey (DFS). METHODS: Two studies were
      carried out in separate populations. The first involved 166 Japanese dental and
      nursing students and assessed internal consistency and test-retest reliability.
      The second involved 2,095 Japanese parents or guardians of school children and
      tested the hypothesis that the conceptual structure of the Japanese translation
      was consistent with the U.S. version using Structural Equation Modeling (SEM).
      RESULTS: In the first study Cronbach alpha ranged from .94 to .96 and test-retest
      reliability (Spearman correlation) ranged from .89 to .92. The intra-class
      correlation coefficients (ICC) was 0.919 (95%CI: 0.892 - 0.940). In the second
      study SEM was used on the covariance matrix of the 20 questions in a random
      sample of 600 questionnaires to evaluate the goodness of fit of the theoretical
      model; and then, in an exploratory manner corrected for specification errors
      until a model that fit the data well was achieved. CONCLUSION: The Japanese
      version of the DFS appears reliable and demonstrates cross-cultural validity. The
      modeling confirms the three factors on which the English language version was
      based.

PMID- 19591676
TI  - Large-scale evaluation of dynamically important residues in proteins predicted by
      the perturbation analysis of a coarse-grained elastic model.
AB  - BACKGROUND: It is increasingly recognized that protein functions often require
      intricate conformational dynamics, which involves a network of key amino acid
      residues that couple spatially separated functional sites. Tremendous efforts
      have been made to identify these key residues by experimental and computational
      means. RESULTS: We have performed a large-scale evaluation of the predictions of
      dynamically important residues by a variety of computational protocols including
      three based on the perturbation and correlation analysis of a coarse-grained
      elastic model. This study is performed for two lists of test cases with >500
      pairs of protein structures. The dynamically important residues predicted by the
      perturbation and correlation analysis are found to be strongly or moderately
      conserved in >67% of test cases. They form a sparse network of residues which are
      clustered both in 3D space and along protein sequence. Their overall conservation
      is attributed to their dynamic role rather than ligand binding or high network
      connectivity. CONCLUSION: By modeling how the protein structural fluctuations
      respond to residue-position-specific perturbations, our highly efficient
      perturbation and correlation analysis can be used to dissect the functional
      conformational changes in various proteins with a residue level of detail. The
      predictions of dynamically important residues serve as promising targets for
      mutational and functional studies.

PMID- 19591678
TI  - The effectiveness of web-based and face-to-face continuing education methods on
      nurses' knowledge about AIDS: a comparative study.
AB  - BACKGROUND: Information about web-based education outcomes in comparison with a
      face-to-face format can help researchers and tutors prepare and deliver future
      web-based or face-to-face courses more efficiently. The aim of this study was to
      compare the effectiveness of web-based and face-to-face continuing education
      methods in improving nurses' knowledge about AIDS. METHODS: A quasi-experimental
      method was used with a pre-test and post-test design. In this study 140 nurses
      with BSc degrees were chosen through a random sampling method and divided into a
      web-based and a face-to-face group by random allocation. For the former group the
      intervention consisted of a web-based course on AIDS; the latter received a 3
      hour lecture course on the same subject. At the beginning and end of the course
      in both groups, the nurses' knowledge was measured by a questionnaire. Pre- and
      post-test scores were compared within and between the groups. RESULTS: The
      results show that there was no significant difference between the groups in
      either the pre-test (t(138) = -1.7, p = 0.096) nor the post-test (t(138) = -1.4,
      p = 0.163) scores in the knowledge test. However, there was a significant
      difference in the pre-test and post-test scores within each group (web-based,
      t(69) = 26, p < .001; face-to-face, t(69) = 24.3, p < .001). CONCLUSION: The web
      based method seems to be as effective as the face-to-face method in the
      continuing education of nurses. Therefore, the web-based method is recommended,
      as complementary to the face-to-face method, for designing and delivering some
      topics of continuing education programs for nurses.

PMID- 19591679
TI  - Analysis of clinical uncertainties by health professionals and patients: an
      example from mental health.
AB  - BACKGROUND: The first step in practising Evidence Based Medicine (EBM) has been
      described as translating clinical uncertainty into a structured and focused
      clinical question that can be used to search the literature to ascertain or
      refute that uncertainty. In this study we focus on questions about treatments for
      schizophrenia posed by mental health professionals and patients to gain a deeper
      understanding about types of questions asked naturally, and whether they can be
      reformulated into structured and focused clinical questions. METHODS: From a
      survey of uncertainties about the treatment of schizophrenia we describe,
      categorise and analyse the type of questions asked by mental health professionals
      and patients about treatment uncertainties for schizophrenia. We explore the
      value of mapping from an unstructured to a structured framework, test inter-rater
      reliability for this task, develop a linguistic taxonomy, and cross tabulate that
      taxonomy with elements of a well structured clinical question. RESULTS: Few of
      the 78 Patients and 161 clinicians spontaneously asked well structured queries
      about treatment uncertainties for schizophrenia. Uncertainties were most commonly
      about drug treatments (45.3% of clinicians and 41% of patients), psychological
      therapies (19.9% of clinicians and 9% of patients) or were unclassifiable.(11.8%
      of clinicians and 16.7% of patients). Few naturally asked questions could be
      classified using the well structured and focused clinical question format (i.e.
      PICO format). A simple linguistic taxonomy better described the types of
      questions people naturally ask. CONCLUSION: People do not spontaneously ask well
      structured clinical questions. Other taxonomies may better capture the nature of
      questions. However, access to EBM resources is greatly facilitated by framing
      enquiries in the language of EBM, such as posing queries in PICO format. People
      do not naturally do this. It may be preferable to identify a way of searching the
      literature that more closely matches the way people naturally ask questions if
      access to information about treatments are to be made more broadly available.

PMID- 19591680
TI  - Systematic review of economic evaluations of human cell-derived wound care
      products for the treatment of venous leg and diabetic foot ulcers.
AB  - BACKGROUND: Tissue engineering is an emerging field. Novel bioengineered skin
      substitutes and genetically derived growth factors offer innovative approaches to
      reduce the burden of diabetic foot and venous leg ulcers for both patients and
      health care systems. However, they frequently are very costly. Based on a
      systematic review of the literature, this study assesses the cost-effectiveness
      of these growth factors and tissue-engineered artificial skin for treating
      chronic wounds. METHODS: On the basis of an extensive explorative search, an
      appropriate algorithm for a systematic database search was developed. The
      following databases were searched: BIOSIS Previews, CRD databases, Cochrane
      Library, EconLit, Embase, Medline, and Web of Science. Only completed and
      published trial- or model-based studies which contained a full economic
      evaluation of growth factors and bioengineered skin substitutes for the treatment
      of chronic wounds were included. Two reviewers independently undertook the
      assessment of study quality. The relevant studies were assessed by a modified
      version of the Consensus on Health Economic Criteria (CHEC) list and a published
      checklist for evaluating model-based economic evaluations. RESULTS: Eleven health
      economic evaluations were included. Three biotechnology products were identified
      for which topical growth factors or bioengineered skin substitutes for the
      treatment of chronic leg ulceration were economically assessed: (1) Apligraf, a
      bilayered living human skin equivalent indicated for the treatment of diabetic
      foot and venous leg ulcers (five studies); (2) Dermagraft, a human fibroblast
      derived dermal substitute, which is indicated only for use in the treatment of
      full-thickness diabetic foot ulcers (one study); (3) REGRANEX Gel, a human
      platelet-derived growth factor for the treatment of deep neuropathic diabetic
      foot ulcers (five studies). The studies considered in this review were of varying
      and partly low methodological quality. They calculated that due to shorter
      treatment periods, fewer complications and fewer inpatient episodes the initial
      cost of the novel biotechnology products may be offset, making the treatment cost
      effective or even cost-saving. The results of most studies were sensitive to
      initial costs of the products and the evidence of effectiveness. CONCLUSION: The
      study results suggest that some growth factors and tissue-engineered artificial
      skin products feature favourable cost-effectiveness ratios in selected patient
      groups with chronic wounds. Despite the limitations of the studies considered, it
      is evident that health care providers and coverage decision makers should take
      not only the high cost of the biotechnology product but the total cost of care
      into account when deciding about the appropriate allocation of their financial
      resources. However, not only the cost-effectiveness but first of all the
      effectiveness of these novel biotechnology products deserve further research.

PMID- 19591681
TI  - Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing
      CYP109B1 from Bacillus subtilis in a two-liquid-phase system.
AB  - BACKGROUND: (+)-Nootkatone (4) is a high added-value compound found in grapefruit
      juice. Allylic oxidation of the sesquiterpene (+)-valencene (1) provides an
      attractive route to this sought-after flavoring. So far, chemical methods to
      produce (+)-nootkatone (4) from (+)-valencene (1) involve unsafe toxic compounds,
      whereas several biotechnological approaches applied yield large amounts of
      undesirable byproducts. In the present work 125 cytochrome P450 enzymes from
      bacteria were tested for regioselective oxidation of (+)-valencene (1) at allylic
      C2-position to produce (+)-nootkatone (4) via cis- (2) or trans-nootkatol (3).
      The P450 activity was supported by the co-expression of putidaredoxin reductase
      (PdR) and putidaredoxin (Pdx) from Pseudomonas putida in Escherichia coli.
      RESULTS: Addressing the whole-cell system, the cytochrome CYP109B1 from Bacillus
      subtilis was found to catalyze the oxidation of (+)-valencene (1) yielding
      nootkatol (2 and 3) and (+)-nootkatone (4). However, when the in vivo
      biooxidation of (+)-valencene (1) with CYP109B1 was carried out in an aqueous
      milieu, a number of undesired multi-oxygenated products has also been observed
      accounting for approximately 35% of the total product. The formation of these
      byproducts was significantly reduced when aqueous-organic two-liquid-phase
      systems with four water immiscible organic solvents - isooctane, n-octane,
      dodecane or hexadecane - were set up, resulting in accumulation of nootkatol (2
      and 3) and (+)-nootkatone (4) of up to 97% of the total product. The best
      productivity of 120 mg l-1 of desired products was achieved within 8 h in the
      system comprising 10% dodecane. CONCLUSION: This study demonstrates that the
      identification of new P450s capable of producing valuable compounds can basically
      be achieved by screening of recombinant P450 libraries. The biphasic reaction
      system described in this work presents an attractive way for the production of
      (+)-nootkatone (4), as it is safe and can easily be controlled and scaled up.

PMID- 19591682
TI  - Measuring patient's expectation and the perception of quality in LASIK services.
AB  - BACKGROUND: LASIK is the use of excimer lasers to treat therapeutic and
      refractive visual disorders, ranging from superficial scars to nearsightedness
      (myopia), and from astigmatism to farsightedness (hyperopia). The purposes of
      this study are to checking the applicability and psychometric properties of the
      SERVQUAL on Lasik surgery population. Second, use SEM methods to investigate the
      loyalty, perceptions and expectations relationship on LASIK surgery. METHODS: The
      method with which this study was conducted was questionnaire development. A total
      of 463 consecutive patients, attending LASIK surgery affiliated with Chung Shan
      Medical University Eye Center, enrolled in this study. All participants were
      asked to complete revised SERVQUAL questionnaires. Student t test, correlation
      test, and ANOVA and factor analyses were used to identify the characters and
      factors of service quality. Paired t test were used to test the gap between
      expectation and perception scores and structural equation modeling was used to
      examine relationships among satisfaction components. RESULTS: The effective
      response rate was 97.3%. Validity was verified by several methods and internal
      reliability Cronbach's alpha was > 0.958. The results from patient's scores were
      very high with an overall score of 6.41(0.66), expectations at 6.68(0.47), and
      perceptions at 6.51(0.57). The gap between expectations and perceptions was
      significant, however, (t = 6.08). Furthermore, there were significant differences
      in the expectation scores among the different jobs. Also, the results showed that
      the higher the education of the patient, the lower their perception score (r = 
      0.10). The factor loading results of factor analysis showed 5 factors of the 22
      items of the SERVQUAL model. The 5 factors of perception explained 72.94% of the
      total variance there; and on expectations it explained 77.12% of the total
      variance of satisfaction scores.The goodness-of-fit summary, of structure
      equation modeling, showed trends in concept on expectations, perceptions, and
      loyalty. CONCLUSION: The results of this research appear to show that the
      SERVQUAL instrument is a useful measurement tool in assessing and monitoring
      service quality in LASIK service, and enabling staff to identify where
      improvements are needed, from the patients' perspective. There were service
      quality gaps in the reliability, assurance, and empathy. This study suggested
      that physicians should increase their discussions with patients; which has, of
      course, already been proven to be an effective way to increase patient's
      satisfaction with medical care, regardless of the procedure received.

PMID- 19591683
TI  - Evaluation of the impact of fibromyalgia on patients' sleep and the content
      validity of two sleep scales.
AB  - BACKGROUND: Disturbed sleep is commonly reported in fibromyalgia (FM). Both the
      Sleep Quality Numeric Rating Scale (NRS) and the Medical Outcomes Study Sleep
      Scale (MOS-Sleep) have demonstrated positive psychometric properties in patients
      with FM. However, these assessments were developed prior to the current
      recommendation to include patient input during the concept elicitation or item
      generation phases. Therefore, the objective of this study was to evaluate the
      impact of FM on participants, including their sleep, and to test the content
      validity of these two sleep measures in FM patients. METHODS: Qualitative
      interviews were conducted in Raleigh, North Carolina and Detroit, Michigan with
      20 adults who reported a physician diagnosis of FM. Sixteen participants were
      female, 13 were white, and the average age was 50 years. Two researchers
      conducted all interviews using a structured guide. RESULTS: Participants
      consistently reported that FM had a debilitating impact on their lives and their
      sleep, particularly getting to sleep and staying asleep. Participants responded
      positively to the Sleep Quality NRS as an assessment of their sleep. The majority
      of participants stated that they would not change the response numbering or
      wording of the item's anchors. Participants also responded positively to the 24
      hour recall period of the Sleep Quality NRS. Participants found the 12-item MOS
      Sleep to be appropriate and relevant; 19 participants indicated the measure
      captured all of their sleep-related symptoms. However, areas for potential
      modification were identified, such as the need to separate the item regarding
      awakening short of breath and awakening with a headache into two separate
      questions. Participants also questioned the relevance of the snoring and
      awakening short of breath items to FM. Half of participants expressed a
      preference for a daily rather than a weekly recall period. CONCLUSION: This study
      demonstrates the significant impact that FM has on patients' lives, particularly
      sleep. While patients with FM were not part of the development of the generic
      sleep assessments that were evaluated, this study provides evidence of their
      content validity, supporting their use in FM studies. Modifications to the MOS
      Sleep may improve the psychometric properties and relevance to patients with FM.

PMID- 19591684
TI  - Chemomodulation of human dendritic cell function by antineoplastic agents in low
      noncytotoxic concentrations.
AB  - The dose-delivery schedule of conventional chemotherapy, which determines its
      efficacy and toxicity, is based on the maximum tolerated dose. This strategy has
      lead to cure and disease control in a significant number of patients but is
      associated with significant short-term and long-term toxicity. Recent data
      demonstrate that moderately low-dose chemotherapy may be efficiently combined
      with immunotherapy, particularly with dendritic cell (DC) vaccines, to improve
      the overall therapeutic efficacy. However, the direct effects of low and ultra
      low concentrations on DCs are still unknown. Here we characterized the effects of
      low noncytotoxic concentrations of different classes of chemotherapeutic agents
      on human DCs in vitro. DCs treated with antimicrotubule agents vincristine,
      vinblastine, and paclitaxel or with antimetabolites 5-aza-2-deoxycytidine and
      methotrexate, showed increased expression of CD83 and CD40 molecules. Expression
      of CD80 on DCs was also stimulated by vinblastine, paclitaxel, azacytidine,
      methotrexate, and mitomycin C used in low nontoxic concentrations. Furthermore, 5
      aza-2-deoxycytidine, methotrexate, and mitomycin C increased the ability of human
      DCs to stimulate proliferation of allogeneic T lymphocytes. Thus, our data
      demonstrate for the first time that in low noncytotoxic concentrations
      chemotherapeutic agents do not induce apoptosis of DCs, but directly enhance DC
      maturation and function. This suggests that modulation of human DCs by
      noncytotoxic concentrations of antineoplastic drugs, i.e. chemomodulation, might
      represent a novel approach for up-regulation of functional activity of resident
      DCs in the tumor microenvironment or improving the efficacy of DCs prepared ex
      vivo for subsequent vaccinations.

PMID- 19591685
TI  - A review of reporting of participant recruitment and retention in RCTs in six
      major journals.
AB  - BACKGROUND: Poor recruitment and retention of participants in randomised
      controlled trials (RCTs) is problematic but common. Clear and detailed reporting
      of participant flow is essential to assess the generalisability and comparability
      of RCTs. Despite improved reporting since the implementation of the CONSORT
      statement, important problems remain. This paper aims: (i) to update and extend
      previous reviews evaluating reporting of participant recruitment and retention in
      RCTs; (ii) to quantify the level of participation throughout RCTs. METHODS: We
      reviewed all reports of RCTs of health care interventions and/or processes with
      individual randomisation, published July-December 2004 in six major journals.
      Short, secondary or interim reports, and Phase I/II trials were excluded. Data
      recorded were: general RCT details; inclusion of flow diagram; participant flow
      throughout trial; reasons for non-participation/withdrawal; target sample sizes.
      RESULTS: 133 reports were reviewed. Overall, 79% included a flow diagram, but
      over a third were incomplete. The majority reported the flow of participants at
      each stage of the trial after randomisation. However, 40% failed to report the
      numbers assessed for eligibility. Percentages of participants retained at each
      stage were high: for example, 90% of eligible individuals were randomised, and
      93% of those randomised were outcome assessed. On average, trials met their
      sample size targets. However, there were some substantial shortfalls: for example
      21% of trials reporting a sample size calculation failed to achieve adequate
      numbers at randomisation, and 48% at outcome assessment. Reporting of losses to
      follow up was variable and difficult to interpret. CONCLUSION: The majority of
      RCTs reported the flow of participants well after randomisation, although only
      two-thirds included a complete flow chart and there was great variability over
      the definition of "lost to follow up". Reporting of participant eligibility was
      poor, making assessments of recruitment practice and external validity difficult.
      Reporting of participant flow throughout RCTs could be improved by small changes
      to the CONSORT chart.

PMID- 19591686
TI  - Radiation-induced cancer after radiotherapy for non-Hodgkin's lymphoma of the
      head and neck: a retrospective study.
AB  - BACKGROUND: survivors of non-Hodgkin's lymphoma (NHL) are well known to be at an
      increased risk of second malignancies. In this study, we evaluated the incidence
      and clinical features of head and neck cancer (HNC) occurring after radiotherapy
      (RT) for NHL. MATERIALS AND METHODS: We investigated the clinical records of 322
      patients who had received RT for early-stage NHL of the head and neck at our
      institute between 1952 and 2000. RESULTS: There were 4 patients with a second HNC
      developing in the irradiated field, consisting of 2 patients with gum cancer, 1
      case with tongue cancer and 1 case with maxillary sinus cancer. The pathological
      diagnosis in all the 4 patients was squamous cell carcinoma (SCC). Two of the
      patients (one with gum cancer and one with maxillary sinus cancer) died of the
      second HNC, while the remaining 2 patients are still living at the time of
      writing after therapy for the second HNC, with neither recurrence of the second
      tumor nor relapse of the primary tumor. The ratio of the observed to the expected
      number (O/E ratio) of a second HNC was calculated to be 12.7 (95%CI, 4.07-35.0),
      and the absolute excess risk (AER) per 10,000 person-years was 13.3. The median
      interval between the RT and the diagnosis of the second HNC was 17.0 years
      (range, 8.7 to 22.7 years). CONCLUSION: The risk of HNC significantly increased
      after RT for early-stage NHL. These results suggest that second HNC can be
      regarded as one of the late complications of RT for NHL of the head and neck.

PMID- 19591687
TI  - Implications of a high-definition multileaf collimator (HD-MLC) on treatment
      planning techniques for stereotactic body radiation therapy (SBRT): a planning
      study.
AB  - PURPOSE: To assess the impact of two multileaf collimator (MLC) systems (2.5 and
      5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity
      modulated radiotherapy, and dynamic conformal arc techniques for stereotactic
      body radiation therapy (SBRT) of liver and lung lesions. METHODS: Twenty-nine
      SBRT plans of primary liver (n=11) and lung (n=18) tumors were the basis of this
      study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based
      plans served as reference, and were designed using static conformal beams
      (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal
      arcs (DCA). Reference plans were either re-optimized or recomputed, with
      identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high
      definition (HD120) MLC system. Dose computation was based on the anisotropic
      analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity
      taken into account. Each plan was normalized such that 100% of the prescription
      dose covered 95% of the planning target volume (PTV). Isodose distributions and
      dose-volume histograms (DVHs) were computed and plans were evaluated with respect
      to target coverage criteria, normal tissue sparing criteria, as well as treatment
      efficiency. RESULTS: Dosimetric differences achieved using M120 and the HD120 MLC
      planning were generally small. Dose conformality improved in 51.7%, 62.1% and
      55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC
      system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT,
      3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves
      demonstrated a decreased volume of normal tissue irradiated to the lower (90%,
      50% and 25%) isodose levels with the HD120 MLC. CONCLUSION: Data derived from the
      present comparative assessment suggest dosimetric merit of the high definition
      MLC system over the millennium MLC system. However, the clinical significance of
      these results warrants further investigation in order to determine whether the
      observed dosimetric advantages translate into outcome improvements.

PMID- 19591688
TI  - Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic
      nasopharyngeal carcinoma: analysis of data from randomized trial between
      radiation alone versus concurrent chemo-radiation (SQNP-01).
AB  - BACKGROUND: Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported
      in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this
      has yet to be conclusively determined. Thus, from our randomized trial of
      radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort
      of tumour samples collected from participants from one referral hospital.
      METHODS: 58 out of 88 patients from this institution had samples available for
      analysis. COX-2 expression levels were stratified by immunohistochemistry, into
      negligible, weak, moderate and strong, and correlated with overall and disease
      specific survivals. RESULTS: 58% had negligible or weak COX-2 expression, while
      14% and 28% had moderate and strong expression respectively. Weak COX-2
      expression conferred a poorer median overall survival, 1.3 years for weak versus
      6.3 years for negligible, 7.8 years, strong and not reached for moderate. There
      was a similar trend for disease specific survival. CONCLUSION: Contrary to
      literature published on other malignancies, our findings seemed to indicate that
      over-expression of COX-2 confer a better prognosis in patients with endemic NPC.
      Larger studies are required to conclusively determine the significance of COX-2
      expression in these patients.

PMID- 19591689
TI  - Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally
      advanced breast cancer.
AB  - BACKGROUND: Despite broad advances in multimodal treatment of locally advanced
      breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The
      aim of this study was to analyze in a retrospective manner the effectiveness of
      concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in
      patients with LABC. METHODS: One hundred twelve patients with LABC (stage IIB
      IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and
      cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide
      500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast
      irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and
      dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and
      dexamethasone 16 mg), and 6-8 weeks later, surgery and two additional courses of
      FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen
      receptor positive patients, hormonal therapy. RESULTS: Stages IIB, IIIA and -B
      were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in
      the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if
      including both the breast and the axillary nodes. Multivariate analysis showed
      that the main determinant of pCR was negative estrogen-receptor status (HR=3.8;
      95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95%
      CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate
      analysis demonstrated that the main DFS determinant was clinical stage (IIB and
      IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local
      recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity
      profile was acceptable. CONCLUSION: This non-conventional multimodal treatment
      has good loco-regional control for LABC. Randomized clinical trials of
      preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

PMID- 19591690
TI  - Patent arterial duct.
AB  - Patent arterial duct (PAD) is a congenital heart abnormality defined as
      persistent patency in term infants older than three months. Isolated PAD is found
      in around 1 in 2000 full term infants. A higher prevalence is found in preterm
      infants, especially those with low birth weight. The female to male ratio is 2:1.
      Most patients are asymptomatic when the duct is small. With a moderate-to-large
      duct, a characteristic continuous heart murmur (loudest in the left upper chest
      or infraclavicular area) is typical. The precordium may be hyperactive and
      peripheral pulses are bounding with a wide pulse pressure. Tachycardia,
      exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large
      shunts may lead to failure to thrive, recurrent infection of the upper
      respiratory tract and congestive heart failure. In the majority of cases of PAD
      there is no identifiable cause. Persistence of the duct is associated with
      chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital
      rubella. Occasional cases are associated with specific genetic defects (trisomy
      21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of
      PAD is uncommon and the usual mechanism of inheritance is considered to be
      polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been
      described in which the mode of inheritance appears to be dominant or recessive.
      Familial incidence of PAD has also been linked to Char syndrome, familial
      thoracic aortic aneurysm/dissection associated with patent arterial duct, and
      familial patent arterial duct and bicuspid aortic valve associated with hand
      abnormalities. Diagnosis is based on clinical examination and confirmed with
      transthoracic echocardiography. Assessment of ductal blood flow can be made using
      colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible,
      as PAD is a normal structure during antenatal life. Conditions with signs and
      symptoms of pulmonary overcirculation secondary to a left-to-right shunt must be
      excluded. Coronary, systemic and pulmonary arteriovenous fistula, peripheral
      pulmonary stenosis and ventricular septal defect with aortic regurgitation and
      collateral vessels must be differentiated from PAD on echocardiogram. In preterm
      infants with symptomatic heart failure secondary to PAD, treatment may be
      achieved by surgical ligation or with medical therapy blocking prostaglandin
      synthesis (indomethacin or ibuprofen). Transcatheter closure of the duct is
      usually indicated in older children. PAD in preterm and low birth weight infants
      is associated with significant co-morbidity and mortality due to haemodynamic
      instability. Asymptomatic patients with a small duct have a normal vital
      prognosis but have a lifetime risk of endocarditis. Patients with moderate-to
      large ducts with significant haemodynamic alterations may develop irreversible
      changes to pulmonary vascularity and pulmonary hypertension.

PMID- 19591691
TI  - Ethics of conducting research in conflict settings.
AB  - Humanitarian agencies are increasingly engaged in research in conflict and post
      conflict settings. This is justified by the need to improve the quality of
      assistance provided in these settings and to collect evidence of the highest
      standard to inform advocacy and policy change. The instability of conflict
      affected areas, and the heightened vulnerability of populations caught in
      conflict, calls for careful consideration of the research methods employed, the
      levels of evidence sought, and ethical requirements. Special attention needs to
      be placed on the feasibility and necessity of doing research in conflict
      settings, and the harm-benefit ratio for potential research participants.

PMID- 19591692
TI  - Influence of the dual ABCB1 and ABCG2 inhibitor tariquidar on the disposition of
      oral imatinib in mice.
AB  - BACKGROUND: Imatinib, a tyrosine kinase inhibitor currently approved for
      treatment of several malignancies, has been shown to be a substrate for multiple
      efflux-transporter proteins, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP).
      The effect of inhibiting these transporters on tissue exposure to imatinib
      remains unclear. OBJECTIVE: To assess the role of these transporters on drug
      disposition, 50 mg/kg imatinib was administered to Balb/C mice, 30 minutes after
      receiving tariquidar (10 mg/kg), an inhibitor of both ABCB1 and ABCG2, or
      vehicle, via oral gavage. METHODS: Quantitative determination of imatinib in
      mouse plasma, liver and brain was performed using a newly-developed and validated
      liquid-chromatography-mass spectrometric method. RESULTS: Exposure to imatinib
      was 2.2-fold higher in plasma, liver and brain in mice that received tariquidar,
      as compared to those that received the vehicle (P = 0.001). The peak plasma
      concentration did not increase substantially, suggesting that tariquidar is
      affecting the distribution, metabolism and/or excretion of imatinib, rather than
      absorption. Though tariquidar increased the absolute exposure of imatinib, the
      brain-to-plasma ratio of imatinib was unaffected. CONCLUSION: This study suggests
      that intentional inhibition of ABCB1 and ABCG2 function at the blood-brain
      barrier is unlikely to significantly improve clinical outcome of imatinib with
      currently used dosing regimens.

PMID- 19591693
TI  - Complexity, cofactors, and the failure of AIDS policy in Africa.
AB  - Global AIDS policy still treats HIV as an exceptional case, abstracting from the
      context in which infection occurs. Policy is based on a simplistic theory of HIV
      causation, and evaluated using outdated tools of health economics. Recent calls
      for a health systems strategy - preventing and treating HIV within a programme of
      comprehensive health care - have not yet influenced the silo approach of AIDS
      policy.Evidence continues to accumulate, showing that multiple factors, such as
      malnutrition, malaria and helminthes, increase the risk of sexual and vertical
      transmission of HIV. Moreover, complementary interventions that reduce viral
      load, improve immune response, and interrupt pathways of transmission could
      increase the effectiveness of antiretroviral drugs and other tools of AIDS
      policy.In health economics, the omission of estimates of increasing returns
      generated by disease or treatment synergies biases cost-effectiveness analysis
      against multiple, yet inexpensive, interventions. Current tools of cost
      effectiveness analysis only identify local maxima in a complex landscape, and can
      play, at best, a marginal role in the epidemic, especially where it is already
      generalized.Cost-effectiveness analyses for HIV that are based on the wrong
      epidemiological model can generate Type III errors: we get precise answers to the
      wrong questions about how to intervene. To control the epidemic, AIDS policy
      needs to utilize an epidemiological model that reflects the interactions of
      biological as well as behavioural variables that determine the course of HIV
      epidemics around the world. Cost-effectiveness analysis can benefit from using
      economic concepts of externalities and increasing returns to incorporate disease
      interactions and beneficial treatment spillovers for coinfections in HIV
      prevention policy.

PMID- 19591695
TI  - Diffusion-weighted magnetic resonance imaging: its uses in otolaryngology.
AB  - Over recent years, there has been an increase in otolaryngology publications
      concerning diffusion-weighted magnetic resonance imaging. The aims of this review
      paper are to summarise the basic principles of diffusion-weighted magnetic
      resonance imaging, and to provide an overview of current otolaryngological
      applications and areas of research. Diffusion-weighted magnetic resonance imaging
      is a radiological technique which has shown promising results in various areas of
      otolaryngology. However, studies of diffusion-weighted magnetic resonance imaging
      are difficult to compare, as different imaging parameters and techniques have
      been used. The role of this imaging modality within otolaryngology is yet to be
      fully elucidated. Diffusion-weighted magnetic resonance imaging may prove to be a
      useful adjunct in both the pre- and post-operative care of otolaryngology
      patients.

PMID- 19591694
TI  - Comparison of cardiac, hepatic, and renal effects of arginine vasopressin and
      noradrenaline during porcine fecal peritonitis: a randomized controlled trial.
AB  - INTRODUCTION: Infusing arginine vasopressin (AVP) in vasodilatory shock usually
      decreases cardiac output and thus systemic oxygen transport. It is still a matter
      of debate whether this vasoconstriction impedes visceral organ blood flow and
      thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis
      whether low-dose AVP is safe with respect to liver, kidney, and heart function
      and organ injury during resuscitated septic shock. METHODS: After intraperitoneal
      inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and
      instrumented pigs were randomly assigned to noradrenaline alone (increments of
      0.05 microg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1
      to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to
      maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension.
      Parameters of systemic and regional hemodynamics (ultrasound flow probes on the
      portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose
      production and whole body glucose oxidation derived from blood glucose isotope
      and expiratory 13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion),
      visceral organ function (blood transaminase activities, bilirubin and creatinine
      concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide
      (exhaled NO and blood nitrate + nitrite levels) and cytokine production
      (interleukin-6 and tumor necrosis factor-alpha blood levels), and myocardial
      function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood
      levels) were measured before and 12, 18, and 24 hours after peritonitis
      induction. Immediate post mortem liver and kidney biopsies were analysed for
      histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining).
      RESULTS: AVP decreased heart rate and cardiac output without otherwise affecting
      heart function and significantly decreased troponin I blood levels. AVP increased
      the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which
      coincided with less severe kidney dysfunction and liver injury, attenuated
      systemic inflammation, and decreased kidney tubular apoptosis. CONCLUSIONS:
      During well-resuscitated septic shock low-dose AVP appears to be safe with
      respect to myocardial function and heart injury and reduces kidney and liver
      damage. It remains to be elucidated whether this is due to the treatment per se
      and/or to the decreased exogenous catecholamine requirements.

PMID- 19591696
TI  - Audit of frequent attendees to an ENT emergency clinic.
AB  - OBJECTIVE: To audit the number of patients attending an ENT emergency clinic more
      than twice in the same clinical episode. METHOD: A completed audit cycle. The
      inclusion criterion for the retrospective arm was patients who had attended the
      ENT emergency clinic more than twice between 1 September to 30 November 2007.
      Data were analysed and interventions implemented. The re-audit, using the same
      inclusion criteria, was done between 1 March to 31 May 2008. RESULTS: The initial
      audit found that 38 patients were seen more than twice in the ENT emergency
      clinic, giving rise to 81 'excess' clinic appointments. After intervention, the
      re-audit identified 19 patients who were seen more than twice in the ENT
      emergency clinic, giving rise to 24 'excess' clinic appointments. CONCLUSION: By
      insisting that patients seen more than twice in the ENT emergency clinic were
      reviewed by a senior clinician, and by introducing a management guideline for
      acute otitis externa, we reduced excess clinic appointments by 70 per cent.

PMID- 19591697
TI  - Application of computer-assisted molecular modeling for immunoassay of low
      molecular weight food contaminants: A review.
AB  - Immunoassay for low molecular weight food contaminants, such as pesticides,
      veterinary drugs, and mycotoxins is now a well-established technique which meets
      the demand for a rapid, reliable, and cost-effective analytical method. However,
      due to limited understanding of the molecular structure of antibody binding sites
      and antigenic epitopes, as well as the intermolecular binding forces that come
      into play, the traditional 'trial and error' method used to develop antibodies
      still remains the method of choice. Therefore, development of enhanced
      immunochemical techniques for specific- and generic-assays, requires new
      approaches for antibody design that will improve affinity and specificity of the
      antibody in a more rapid and economic manner. Computer-assisted molecular
      modeling (CAMM) has been demonstrated to be a useful tool to help the
      immunochemist develop immunoassays. CAMM methods can be used to help direct
      improvements to important antibody features, and can provide insights into the
      effects of molecular structure on biological activity that are difficult or
      impossible to obtain in any other way. In this review, we briefly summarize
      applications of CAMM in immunoassay development, including assisting in hapten
      design, explaining cross-reactivity, modeling antibody-antigen interactions, and
      providing insights into the effects of the mouse body temperature on the three
      dimensional conformation of a hapten during antibody production. The fundamentals
      and theory, programs and software, limitations, and prospects of CAMM in
      immunoassay development were also discussed.

PMID- 19591699
TI  - Multi-wavelength HPLC fingerprints from complex substances: An exploratory
      chemometrics study of the Cassia seed example.
AB  - Multi-wavelength fingerprints of Cassia seed, a traditional Chinese medicine
      (TCM), were collected by high-performance liquid chromatography (HPLC) at two
      wavelengths with the use of diode array detection. The two data sets of
      chromatograms were combined by the data fusion-based method. This data set of
      fingerprints was compared separately with the two data sets collected at each of
      the two wavelengths. It was demonstrated with the use of principal component
      analysis (PCA), that multi-wavelength fingerprints provided a much improved
      representation of the differences in the samples. Thereafter, the multi
      wavelength fingerprint data set was submitted for classification to a suite of
      chemometrics methods viz. fuzzy clustering (FC), SIMCA and the rank ordering MCDM
      PROMETHEE and GAIA. Each method highlighted different properties of the data
      matrix according to the fingerprints from different types of Cassia seeds. In
      general, the PROMETHEE and GAIA MCDM methods provided the most comprehensive
      information for matching and discrimination of the fingerprints, and appeared to
      be best suited for quality assurance purposes for these and similar types of
      sample.

PMID- 19591698
TI  - Determination of phosphorus, sulfur and the halogens using high-temperature
      molecular absorption spectrometry in flames and furnaces--A review.
AB  - The literature about the investigation of molecular spectra of phosphorus, sulfur
      and the halogens in flames and furnaces, and the use of these spectra for the
      determination of these non-metals has been reviewed. Most of the investigations
      were carried out using conventional atomic absorption spectrometers, and there
      were in essence two different approaches. In the first one, dual-channel
      spectrometers with a hydrogen or deuterium lamp were used, applying the two-line
      method for background correction; in the second one, a line source was used that
      emitted an atomic line, which overlapped with the molecular spectrum. The first
      approach had the advantage that any spectral interval could be accessed, but it
      was susceptible to spectral interference; the second one had the advantage that
      the conventional background correction systems could be used to minimize spectral
      interferences, but had the problem that an atomic line had to be found, which was
      overlapping sufficiently well with the maximum of the molecular absorption
      spectrum. More recently a variety of molecular absorption spectra were
      investigated using a low-resolution polychromator with a CCD array detector, but
      no attempt was made to use this approach for quantitative determination of non
      metals. The recent introduction and commercial availability of high-resolution
      continuum source atomic absorption spectrometers is offering completely new
      possibilities for molecular absorption spectrometry and its use for the
      determination of non-metals. The use of a high-intensity continuum source
      together with a high-resolution spectrometer and a CCD array detector makes
      possible selecting the optimum wavelength for the determination and to exclude
      most spectral interferences.

PMID- 19591700
TI  - A reusable capacitive immunosensor for detection of Salmonella spp. based on
      grafted ethylene diamine and self-assembled gold nanoparticle monolayers.
AB  - Fabrication of a novel capacitive immunosensor based on grafted ethylene diamine
      and self-assembled gold nanoparticle monolayer on glassy carbon electrode for the
      detection of Salmonella spp. is described for the first time. In the present
      study, the Salmonella spp. monoclonal antibodies (denoted as McAbs) was
      immobilized on gold nanoparticles. Interaction of McAbs and Salmonella spp. was
      detected directly using the electrochemical impedance spectroscopy (EIS)
      technique. The experimental results showed that the concentration of antigen was
      measured through the relative change in capacitance in the corresponding specific
      binding of Salmonella spp. and McAbs. Under the optimized conditions, the
      relative changes in capacitance were proportional to the logarithmic values of
      Salmonella spp. concentrations in the range of 1.0 x 10(2) to 1.0 x 10(5) CFU mL(
      1) (r = 0.991) with the detection limit of 1.0 x 10(2) CFU mL(-1). The stability
      of proposed immunosensor could be estimated by determining the relative change in
      capacitance, which remained almost the same in two months and decreased gradually
      to 85.3% of initial value after four months' storage. The used immunosensor could
      be regenerated repeatedly by immersing in glycine-HCl buffer solution (pH 2.8).
      Finally, the proposed immunosensor was successfully used for the detection of
      Salmonella spp. in lab-processed commercial pork samples.

PMID- 19591701
TI  - Evaluation of multi-walled carbon nanotubes as solid-phase extraction adsorbents
      of pesticides from agricultural, ornamental and forestal soils.
AB  - A new, simple and cost-effective method based on the use of multi-walled carbon
      nanotubes (MWCNTs) as solid-phase extraction stationary phases is proposed for
      the determination of a group of seven organophosphorus pesticides (i.e.
      ethoprophos, diazinon, chlorpyriphos-methyl, fenitrothion, malathion,
      chlorpyriphos and phosmet) and one thiadiazine (buprofezin) in different kinds of
      soil samples (forestal, ornamental and agricultural) using gas chromatography
      with nitrogen phosphorus detection. Soils were first ultrasound extracted with 10
      mL 1:1 methanol/acetonitrile (v/v) and the evaporated extract redissolved in 20
      mL water (pH 6.0) was passed through 100 mg of MWCNTs of 10-15 nm o.d., 2-6 nm
      i.d. and 0.1-10 microm length. Elution was carried out with 20 mL
      dichloromethane. The method was validated in terms of linearity, precision,
      recovery, accuracy and selectivity. Matrix-matched calibration was carried out
      for each type of soil since statistical differences between the calibration
      curves constructed in pure solvent and in the reconstituted soil extract were
      found for most of the pesticides under study. Recovery values of spiked samples
      ranged between 54 and 91% for the three types of soils (limits of detection
      (LODs) between 2.97 and 9.49 ngg(-1)), except for chlorpyrifos, chlorpyrifos
      methyl and buprofezin which ranged between 12 and 54% (LODs between 3.14 and 72.4
      ngg(-1)), which are the pesticides with the highest soil organic carbon sorption
      coefficient (K(OC)) values. Using a one-sample test (Student's t-test) with
      fortified samples at two concentration levels in each type of soil, no
      significant differences were observed between the real and the experimental
      values (accuracy percentages ranged between 87 and 117%). It is the first time
      that the adsorptive potential of MWCNTs for the extraction of organophosphorus
      pesticides from soils is investigated.

PMID- 19591702
TI  - Determination of organochlorine pesticides in water using dynamic hook-type
      liquid-phase microextraction.
AB  - We developed a simple and efficient headspace liquid-phase microextraction (LPME)
      technique named dynamic hook-type liquid-phase microextraction (DHT-LPME) and
      used it in combination with gas chromatography-mass spectrometry (GC-MS) and an
      electron capture detector (ECD). Aqueous specimens of organochlorine pesticides
      (OCPs) were used as model compounds to demonstrate the effectiveness of the
      technique. In the present study, the calibration curves were linear over at least
      2 orders of magnitude with R(2) values of 0.997. The method detection limits
      (MDLs) varied from 2 to 44.0 ngL(-1). The precision of DHT-LPME ranged from 6.5
      to 14.4%. The relative recoveries of OCPs in rainwater were more than 84.2%.
      Enrichment factors (EF) in the range 275-1127 were obtained using DHT-LPME.

PMID- 19591703
TI  - Determination of selected polychlorinated biphenyls in water samples by
      ultrasound-assisted emulsification-microextraction and gas chromatography-mass
      selective detection.
AB  - Ultrasound-assisted emulsification-microextraction (USAEME) procedure was
      developed for the determination of selected polychlorinated biphenyls (PCBs) in
      10 mL of water samples by gas chromatography-mass-selective detection. After
      determination of the most suitable solvent and extraction time, several other
      parameters including solvent volume, centrifugation time and ionic strength of
      the sample were optimized using a 2(3) factorial experimental design. The
      optimized USAEME procedure used 200 microL of chloroform as extraction solvent,
      10 min of extraction with no ionic strength adjustment at 25 degrees C and 5 min
      of centrifugation at 4000 rpm. The limits of detection ranged from 14 ngL(-1)
      (for PCB153) to 30 ngL(-1) (for PCB101). Recoveries of PCBs from fortified
      distilled water are over 80% for three different fortification levels between 0.1
      and 5 microgL(-1) and relative standard deviations of the recoveries are below
      10%. The performance of the proposed method was compared with those involving
      traditional liquid-liquid extraction (LLE) and solid phase extraction (SPE) on
      the real water samples (i.e., tap and well water as well as domestic and
      industrial wastewaters, etc.) and comparable efficiencies were obtained. The
      proposed USAEME procedure has been demonstrated to be viable, simple, rapid and
      easy to use for residue analysis of PCBs in water samples.

PMID- 19591704
TI  - Investigation of oxidation and tautomerization of a recently synthesized Schiff
      base in micellar media using multivariate curve resolution alternative least
      squares and rank annihilation factor analysis methods.
AB  - The oxidation of the recently synthesized Schiff base 3,6-bis((2-aminoethyl-5-Br
      salicyliden)thio)pyridazine (PABST) with hydrogen peroxide was investigated using
      spectrophotometric studies. The reaction rate order and observed rate constant of
      the oxidation reaction was obtained in the mixture of N,N-dimethylformamide
      (DMF):water (30:70, v/v) at pH 10 using multivariate cure resolution alternative
      least squares (MCR-ALS) method and rank annihilation factor analysis (RAFA). The
      effective parameters on the oxidation rate constant such as percents of DMF, the
      effect of transition metals like Cu(2+), Zn(2+), Mn(2+) and Hg(2+) and the
      presence of surfactants were investigated. The keto-enol equilibria in DMF:water
      (30:70, v/v) solution at pH 7.6 was also investigated in the presence of
      surfactants. At concentrations above critical micelle concentration (cmc) of
      cationic surfactant cetyltrimethylammonium bromide (CTAB), the keto form was the
      predominant species, while at concentrations above cmc of anionic surfactant
      sodium dodecyl sulfate (SDS), the enol form was the predominant species. The
      kinetic reaction order and the rate constant of tautomerization in micellar
      medium were obtained using MCR-ALS and RAFA. The results obtained by both the
      methods were in a good agreement with each other. Also the effect of different
      volume percents of DMF on the rate constant of tautomerization was investigated.
      The neutral surfactant (Triton X-100) had no effect on tautomerization
      equilibrium.

PMID- 19591705
TI  - Fabrication of dissolved O2 metric uric acid biosensor using uricase epoxy resin
      biocomposite membrane.
AB  - Uricase purified from 20-day-old leaves of cowpea was immobilized on to epoxy
      resin membrane with 80% retention of initial activity of free enzyme and a
      conjugation yield of 0.056 mg/cm(2). The uricase epoxy resin bioconjugate
      membrane was mounted over the sensing part of the combined electrode of
      'Aqualytic' dissolved O(2) (DO) meter to construct a uric acid biosensor. The
      biosensor measures the depletion of dissolved O(2) during the oxidation of uric
      acid by immobilized uricase, which is directly proportional to uric acid
      concentration. The biosensor showed optimum response within 10-12s at a pH 8.5
      and 35 degrees C. A linear relationship was found between uric acid concentration
      from 0.025 to 0.1 mM and O(2) (mg/l) consumed. The biosensor was employed for
      measurement of uric acid in serum. The mean value of uric acid in serum was 4.92
      mg/dl in apparently healthy males and 3.11 mg/dl in apparently healthy females.
      The mean analytic recoveries of added uric acid in reaction mixture (8.9 and 9.8
      mg/dl) were 93.6 +/- 2.34 and 87.18 +/- 3.17% respectively. The within and
      between batch CVs were < 6.5 and < 5.0%, respectively. The serum uric acid values
      obtained by present method and standard enzymic colorimetric method, showed a
      good correlation (r - 0.996) and regression equation being y - 0.984x + 0.0674.
      Among the various metabolites tested only, glucose (11%), urea (38%), NaCl (25%)
      and cholesterol (13%) and ascorbic acid (56%) caused decrease, while, MgSO(4) and
      CaCl(2) had no effect on immobilized enzyme. The enzyme electrode showed only 32%
      decrease during its use for 100 times over a period of 60 days at 4 degrees C.

PMID- 19591706
TI  - Single- and multi-analyte determination of gonadotropic hormones in urine by
      Surface Plasmon Resonance immunoassay.
AB  - Single- and multi-analyte detection of two gonadotropic hormones (follicle
      stimulating hormone (hFSH) and luteinizing hormone (hLH)) was achieved by a
      Surface Plasmon Resonance (SPR) immunoassay on untreated human urine samples.
      Multi-analyte detection was accomplished using two alternative formats which are
      based in the individual or simultaneous immobilization of the hormones on the
      sensor surface. The lowest detection limit for both hormones in urine was found
      to be 1 ng mL(-1), which in international units (IU) in terms of the World Health
      Organization (WHO) standards represents 8 mIU mL(-1) of hLH and 14 mIU mL(-1) of
      hFSH, respectively. The reliability of the assay was demonstrated by intra- and
      inter-assay variabilities < 6%, chip-to-chip variabilities < 5%, recoveries in
      the range of 80-120% and stability of the sensor response through more than 100
      measurements. The sensitivity of this biosensing methodology renders it in a
      useful technique for the diagnosis of reproductive disorders, as well as for
      fertility monitoring.

PMID- 19591707
TI  - Organically nanoporous silica gel based on carbon paste electrode for
      potentiometric detection of trace Cr(III).
AB  - A new ion-selective electrode (ISE) for the detection of trace chromium(III) was
      designed by using 2-acetylpyridine and nanoporous silica gel (APNSG)
      functionalized carbon paste electrode (CPE). The presence of APNSG acted as not
      only a paste binder, but also a reactive material. With 7.5 wt% APNSG
      proportions, the developed electrode exhibited wide dynamic range of 1.0 x 10(-8)
      to 1.0 x 10(-3) M toward Cr(III) with a detection limit of 8.0 x 10(-9) M and a
      Nernstian slope of 19.8 +/- 0.2 mV decade(-1). The as-prepared electrode
      displayed rapid response (approximately 55 s), long-time stability, and high
      sensitivity. Moreover, the potentiometric responses could be carried out with
      wide pH range of 1.5-5.0. In addition, the content of Cr(III) in food samples,
      e.g. coffee and tea leaves, has been assayed by the developed electrode, atomic
      absorption spectrophotometer (AAS) and atomic emission spectrometer (ICP-AES),
      respectively, and consistent results were obtained. Importantly, the response
      mechanism of the proposed electrode was investigated by using AC impedance and UV
      vis spectroscopy.

PMID- 19591709
TI  - A highly efficient capillary electrophoresis-based method for size determination
      of water-soluble CdSe/ZnS core-shell quantum dots.
AB  - This paper describes a highly efficient method for size determination of water
      soluble CdSe/ZnS core-shell quantum dots (QDs) by capillary electrophoresis (CE)
      using polymer additive as sieving medium. The influence of some factors, such as
      kinds and concentrations of the sieving medium, pH, concentrations of the
      background electrolyte (BGE) and applied voltage, on the separation of QDs was
      investigated. Under the optimal separation conditions, four different sized QDs
      were successfully separated, and the relative standard deviation (RSD) of the
      migration times for these QDs was below 1.013%. In addition, an equation was fit
      by taking into account the correlation existing between the electrophoretic
      mobilities and the sizes of a set of QDs. The feasibility of this equation to
      measure the sizes of other QDs was confirmed by comparison with the sizes
      obtained by transmission electron microscopy (TEM) experiment. This work offers a
      novel method for size determination of QDs, and provides an important reference
      on the study of QDs based on CE.

PMID- 19591708
TI  - High sensitive determination of zinc with novel water-soluble small molecular
      fluorescent sensor.
AB  - A high sensitive method of quantitative analysis for the determination of zinc in
      the nutrition supplements has been developed by using a novel water-soluble
      fluorescent sensor HQ3: (8-pyridylmethyloxy-2-methyl-quinoline). Under the
      optimized condition of 67 mM phosphate buffer, pH 7.4, and 5% (v/v) DMSO, the
      zinc concentration showed good linear relationship with fluorescence intensity in
      the range of 7.5 x 10(-8) to 2.5 x 10(-5) M with the detection limit of 1.5 x 10(
      8) M. HQ3 exhibited high selectivity to zinc comparing with other metal ions
      except for cadmium. The developed analytical method was successfully used for
      determining the content of zinc in a real sample of zinc gluconate solution of
      Sanchine.

PMID- 19591710
TI  - Development of high performance liquid chromatography method for buspirone in
      rabbit serum: Application to pharmacokinetic study.
AB  - A simple and sensitive high performance liquid chromatographic (HPLC) method for
      quantification of buspirone (BUSP) in rabbit serum was developed and validated.
      BUSP and internal standard (IS), diltiazem hydrochloride were extracted into
      dichloromethane and separated using an isocratic mobile phase, on a Kromasil C(8)
      column. The eluent was monitored by UV detector at 235 nm and at a flow rate of
      1.0 mL min(-1). The linearity range of proposed method was 1-3000 ng mL(-1). The
      intra-day and inter-day coefficient of variation and percent error values of the
      assay method were less than 15% and mean recovery was more than 97 and 96% for
      BUSP and IS, respectively. The method was found to be precise, accurate, and
      specific during the study. The method was successfully applied for
      pharmacokinetic study of buspirone after application of reservoir based
      transdermal therapeutic system of BUSP to rabbits.

PMID- 19591711
TI  - Investigation of the colourants used in icons of the Cretan School of
      iconography.
AB  - The red shades of 13 icons (15th-17th century) of the Cretan School of
      iconography are investigated in detail to identify the inorganic and organic
      colouring materials comprising the paint layers. Examination of sample cross
      sections is performed with optical microscopy. Micro-Raman spectroscopy and high
      performance liquid chromatography (HPLC) coupled to a photodiode array detector
      are employed for the identification of the inorganic and organic colouring
      materials, respectively. The results reveal the extensive use of coccid dyes by
      the Cretan painters: kermes (Kermes vermilio Planchon) is found in icons dated
      before the middle 16th century and cochineal in icons created several decades
      after the discovery of the New World. Other dyestuffs detected in the historical
      samples are madder (possibly Rubia tinctorum L., according to HPLC profiles),
      soluble redwood and indigoid dyes. Organic dyes were used by the painters as
      exclusive colouring matters (or glazes) or in mixtures with inorganic pigments,
      such as red ochre, cinnabar, minium, azurite lead white and carbon black. Liquid
      chromatography with mass spectrometry (LC-MS) coupled to a negative electrospray
      ionization mode is employed to provide information on the identity of some
      unknown colouring components, of the aforementioned dyes, detected in the
      historical samples. The results suggest that (i) the type B compound (also known
      as Bra') is a dehydro-brazilein product and (ii) the deprotonated molecular ion
      of the type C compound corresponds to m/z - 243. Both compounds are commonly used
      as markers for the identification of soluble redwood in historical samples. LC-MS
      analysis of cochineal shows that the dcIV and dcVII components are isomeric with
      carminic acid, as it has been recently suggested. Finally, LC-MS is employed to
      identify and record kermesic and flavokermesic acid in kermes and rubiadin in
      wild madder.

PMID- 19591715
TI  - Reforming our health care system: ENA brings your voice to the table.

PMID- 19591713
TI  - Selective accumulation of harmful compounds by the DNA-inorganic hybrid
      immobilized glass bead.
AB  - Previously, we reported the DNA-inorganic hybrid material including double
      stranded DNA by mixing the aqueous DNA solution and silane coupling reagents.
      Here, we immobilized the DNA-inorganic hybrid material onto the glass bead and
      prepared the DNA-immobilized glass bead column. The DNA-immobilized glass beads
      were stable in water and the amount of eluted DNA from the DNA-glass beads did
      not change for more than 1 week. Additionally, this DNA-immobilized column
      selectively accumulated the harmful compounds with the planar structure, such as
      dioxin- and polychlorinated biphenyl (PCB)-derivatives, and these accumulation
      percentages were 50-70%. Furthermore, the DNA-immobilized glass bead was recycled
      nine times by the application of ethanol solution and the accumulative ratio was
      maintained at more than 60% and did not appear to be decreasing. Therefore, these
      DNA-columns might have a potential for the selective removal and separation of
      DNA-intercalating molecules and harmful compounds with the planar structure from
      experimental or industrial drainages.

PMID- 19591712
TI  - Applying Parallel Factor Analysis models to HPLC diode array detector datasets
      reveals strain dependent regulation of polyketide biosynthesis in Fusarium
      graminearum, Fusarium culmorum and Fusarium pseudograminearum.
AB  - Fungal secondary metabolites confer an indiscriminate resource of bioactive
      compounds with both pharmaceutical and industrial relevance. Synthesis of these
      compounds is tightly controlled through regulatory networks. These networks act
      in response to the environmental conditions in which the fungus grows. One class
      of fungal secondary metabolites that have drawn increased attention, is the
      polyketides produced by a high number of fungi and bacteria. The increasing
      number of publicly available genomic sequences of filamentous fungi, combined
      with new and highly efficient DNA-cloning techniques, has allowed the use of new
      efficient approaches to study the regulation and synthesis of these compounds.
      With the availability of new molecular genetic tools, a new bottleneck has
      occurred in fungal molecular biology; the analytical chemical analysis of the
      generated transgenic mutants. In this study, a method based on PARAFAC data
      analysis of HPLC data is presented and shown useful for gaining overview of
      complex and diverse datasets. Further, the strain specific and nutrient dependent
      regulation of polyketide synthesis is discussed.

PMID- 19591716
TI  - Peer review: the art of supporting colleagues and advancing our profession.

PMID- 19591717
TI  - International sports nursing special interest group.

PMID- 19591718
TI  - Door-to-ECG time and gender equity.

PMID- 19591719
TI  - Screening out does little to address ED overcrowding.

PMID- 19591721
TI  - The impact of a sexual assault/domestic violence program on ED care.
AB  - INTRODUCTION: Examination and management of the sexually assaulted patient
      comprise a complex task. On-call nurses with advanced training are used in some
      hospitals, but their impact on patient care and appropriate forensic examination
      is largely unknown. We evaluated the impact of the introduction of a sexual
      assault/domestic violence program (SADVP) on ED flow, comprehensive patient care,
      and collection of forensic evidence. METHODS: Patients presenting to the 2
      emergency departments in the Kingston area (Ontario, Canada) (population,
      250,000) after sexual assault were compared during 2 time periods: (1) before
      SADVP implementation (January 2001 through August 2004) and (2) after SADVP
      implementation (September 2004 to August 2006). ED, hospital discharge, SADVP,
      and police records were reviewed. Data abstraction included patient demographics,
      assault characteristics, forensic examination results, and treatment protocols.
      RESULTS: The incidence of patients presenting with a complaint of sexual assault
      doubled (61 cases before SADVP implementation and 92 cases after SADVP
      implementation). Median times to initial clinical evaluation were lower in the
      post-SADVP group (20 minutes vs 33 minutes, P = .04). Patients in the post-SADVP
      group reported less vaginal/anal penetration (77% vs 98%, P < .001) and had fewer
      genital injuries (13% vs 39%, P = .007); other sexual assault characteristics
      were similar between the 2 study periods. Forensic kits were completed more often
      in the post-SADVP group (77% vs 66%, P = .18). Pregnancy and sexually transmitted
      disease prophylaxis was offered more consistently after SADVP implementation (98%
      vs 85%, P = .007), as was counseling (100% vs 95%, P = .06). DISCUSSION: The
      profile of patients observed after SADVP implementation changed to include less
      stereotypical sexual assaults. Introduction of the SADVP decreased wait times for
      sexually assaulted patients, despite the need for the on-call nurses to attend
      the emergency department. This program also showed higher completion on a number
      of important indicators of quality of care: forensic kits, counseling, and
      pregnancy and sexually transmitted disease prophylaxis.

PMID- 19591722
TI  - Can education and staff-based participatory research change nursing practice in
      an era of ED overcrowding? A focus group study.
AB  - INTRODUCTION: In our facility an operational process intervention was implemented
      to decrease overcrowding. The intervention consisted of implementing criteria
      (developed from a series of 8 interactive workshops led by the investigators with
      all charge and staff nurses) describing when we should "close the waiting room."
      The purpose of this study was to explore the charge nurses' perceptions of the
      intervention and their experiences with implementation several months after the
      operational change began. METHODS: All charge nurses were invited to attend 1 of
      2 focus groups that elicited participants' knowledge of the closing criteria as
      well as their use and perceptions of the criteria. Participants were asked to
      identify how often they had been able to close the waiting room or keep it closed
      and to note whether they used the developed criteria. Barriers and facilitators
      to closing the waiting room were also discussed. RESULTS: Charge nurses had
      internalized the criteria and reported that most of the time the waiting room was
      often closed between the hours of 3 and 9 am. Evening charge nurses, in
      particular, reported feeling a positive impact from waiting room closure during
      these hours earlier in the day. Facilitators included charge nurses receiving
      positive feedback from patients and perceiving an improvement in patient safety
      as fewer patients were waiting. Specific barriers included negative staff
      attitudes and hospital overcrowding. DISCUSSION: Feedback from focus group
      analysis with charge nurses responsible for closing the ED waiting room suggests
      that the operational change has been positive because of the staff-based
      participatory research methodology used to create the intervention.

PMID- 19591724
TI  - Questioning nursing competences in emergency health care.
AB  - INTRODUCTION: Medical and technologic developments entail new competence demands
      in emergency health care, and it follows that head nurses must recognize and
      create prerequisites, as well as evaluate the competence of registered nurses.
      The aim of this study is to describe head nurses' conceptions of emergency
      nursing competence needs and their responsibility for creating prerequisites of
      competence development in emergency nursing. METHODS: A 24-item questionnaire was
      sent to all the head nurses (N = 79) of all the existing emergency departments in
      Sweden. The response rate was 73%, and in the analysis of the data, descriptive
      statistics were used. RESULTS: According to the head nurses, basic nursing
      education does not provide sufficient emergency nursing competence. Consequently,
      there is a need for supplementary formal emergency nursing education.
      Furthermore, most of the head nurses have inadequate strategies for evaluating
      competence development, and economic and personnel resources are insufficient to
      meet the educational needs. A minority of the head nurses consider that they have
      full responsibility for creating the prerequisites of the competence development
      of nurses. DISCUSSION: To ensure sufficient nursing competence in emergency
      health care organizations, there is a need to establish competence demands in
      emergency nursing and evaluate strategies for competence development. The
      establishment of a Swedish emergency nurses association would be important for
      the development of national guidelines of emergency nursing as well as to
      facilitate the interpretation and concretizing of rules and legislation and to
      promote questions related to research, development, and education in emergency
      nursing. With national guidelines and recommendations, the head nurses'
      responsibilities for the development of nurses' skills would be clarified.

PMID- 19591723
TI  - The use of topical anesthesia during intravenous catheter insertion in adults: a
      comparison of pain scores using LMX-4 versus placebo.
AB  - INTRODUCTION: Intravenous (IV) catheter placement is an extremely common painful
      procedure performed in all ages and healthcare settings, more often than not
      without anesthetics, despite clear research and guidelines demonstrating their
      effectiveness. This study examined differences in pain scores following topical
      anesthetic and placebo application, in a sample of healthy adult volunteers
      experiencing IV catheterization. METHODS: During this prospective, placebo
      controlled, double-blind study, 43 subjects were randomized to receive LMX-4 on
      one hand and hand cream on the other 30 minutes prior to IV catheterization.
      Paired t-tests were used to measure the difference in pain scores between hands.
      Pain scores were reported utilizing a visual analog scale (0-10 cm) immediately
      after each stick. As a control, the difficulty of the IV stick was rated on a 0
      10 cm scale and recorded by the nurse who started the IV. RESULTS: The mean pain
      score and standard deviation reported for the LMX-4 hand was 3.2 (SD=2.25, range,
      0-8.5 cm), while the placebo hand was 4.67 (SD=2.25, range, 0.25-10 mm). The mean
      paired difference between LMX-4 and placebo hands was -1.37 (95% CI; -2.2, 
      0.49); subjects receiving LMX-4 reported clinically as well as statistically
      significant pain reductions (t=-3.17, p=0.003). When adjusted for difficulty of
      stick, pain scores continued to remain lower in the LMX-4 hand. DISCUSSION: These
      findings suggest that the topical use of LMX-4 anesthetic cream is a viable
      option for reducing the pain associated with IV catheter insertion in adults.

PMID- 19591725
TI  - Acute pain assessment and pharmacological management practices for the older
      adult with a hip fracture: review of ED trends.
AB  - INTRODUCTION: This article examines acute pain assessment and pharmacological
      management in the emergency department that occurred over a period of time after
      the release of the new pain assessment and management compliance standards of the
      Joint Commission on Accreditation of Healthcare Organizations (JCAHO) for
      accredited health care organizations. Data were available from that collected for
      a large-scale study testing a Translating Research into Practice intervention to
      promote use of evidence-based practices for acute pain management in older
      adults. METHODS: Medical records were abstracted from hospitalized older adult
      patients with hip fractures admitted through the emergency department (N = 1454).
      Records were from 12 acute care hospitals of patients receiving care in the
      emergency departments from 3 different periods between 2000 and 2002. Major
      variables examined were (1) pain assessment practices and (2) pharmacological
      pain treatment practices derived from an Evidence-based Guideline on Acute Pain
      Management in Older Adults. RESULTS: Trends over time illustrate improvements in
      pain assessment practices, with almost all patients having some documentation
      related to pain (99% in 2002), although only 54.4% had pain assessed with a
      numeric rating scale, 4.2% with a non-numeric rating scale (such as verbal
      descriptor or faces scale), and 7.4% with nonverbal pain behaviors. Thus, 34% of
      patients had no objective assessment of pain documented. The mean pain intensity
      reported remained high (6.8 to 7.2 out of 10) across the 3 periods. By the end of
      the study's final data collection point in 2002, only 60% of patients had any
      analgesic ordered, with more than half of this group (59%) having an opioid
      ordered. Of those administered an analgesic, more than 90% received an opioid.
      Practice improvements were noted over time in a decline in intramuscular opioid
      administration and overall meperidine administration and an increase in morphine
      as the opioid of choice in this setting. DISCUSSION: Pain assessment and
      management practices in the emergency departments showed improvements over time
      following the release of JCAHO standards for pain management. However, the care
      documented does not consistently represent best practices for all patients.

PMID- 19591726
TI  - Responding to the shootings at Virginia Tech: planning and preparedness.

PMID- 19591727
TI  - Prehospital use of continuous positive airway pressure: implications for the
      emergency department.

PMID- 19591728
TI  - The role of the emergency nurse in improving care of the patient with ST
      elevation myocardial infarction: perspectives of the RACE nurse leadership.

PMID- 19591729
TI  - A guarantee to a community.

PMID- 19591731
TI  - Integrating physician response into an academic medical center emergency
      operations response plan.

PMID- 19591730
TI  - The sequencing of medication administration in the management of hyperkalemia.

PMID- 19591732
TI  - A 44-year-old man with neurocysticercosis.

PMID- 19591734
TI  - Safe haven laws.

PMID- 19591735
TI  - Leading the revolution: supporting and sustaining a culture of safety in the
      emergency department.

PMID- 19591737
TI  - Access to care and ED crowding: the impact of our constricting economy.

PMID- 19591736
TI  - Caution: all "medrols" are not the same.

PMID- 19591738
TI  - Library and information literacy.

PMID- 19591739
TI  - Sleep and motor vehicle crash risk.

PMID- 19591740
TI  - Volunteer nursing instructor, Dhaka, Bangladesh.

PMID- 19591742
TI  - Making education stick!

PMID- 19591743
TI  - Reducing pain in pediatric procedures in the emergency department.

PMID- 19591744
TI  - Antibiotic balancing act: weighing the risks.

PMID- 19591745
TI  - A tale of two mechanisms: blunt carotid artery injury in a stabbing victim.

PMID- 19591746
TI  - When trauma walks into triage.

PMID- 19591747
TI  - Management of cardiogenic shock: focus on tissue perfusion. Foreword.

PMID- 19591748
TI  - Management of cardiogenic shock: focus on tissue perfusion.
AB  - Cardiogenic shock (CS) may result from ischemic heart disease, cardiomyopathy,
      valvular heart disease, inflammation, myocardial contusion, and cardiac surgery.
      CS is the leading cause of in-hospital death in patients with acute myocardial
      infarction. Although early revascularization strategies have resulted in a better
      prognosis, in-hospital mortality from CS remains exceptionally high. Notably,
      long-term annual mortality is similar in survivors of CS relative to patients
      with myocardial infarction without shock. This underlines the importance of
      aggressive support of the failing heart in the acute phase of CS. Because CS
      reflects a state of hypoperfusion induced by heart failure, management of CS
      should aim at improving cardiac function as well as at optimization of tissue
      perfusion. This review evaluates the current treatment of CS. In addition, novel
      approaches to monitor and modulate peripheral circulation at the bedside are
      highlighted. It is expected that these techniques will improve our understanding
      of the pathogenesis of CS and will offer new opportunities to guide therapy in CS
      patients to improve long-term prognosis.

PMID- 19591749
TI  - Securing the health of disadvantaged women: a critical investigation of tobacco
      control policy effects on women worldwide.

PMID- 19591750
TI  - Union women, the tobacco industry, and excise taxes: a lesson in unintended
      consequences.
AB  - Between 1987 and 1997, the tobacco industry used the issue of cigarette excise
      tax increases to create a political partnership with the Coalition of Labor Union
      Women (CLUW), a group representing female trade unionists in the U.S. This paper
      documents how the industry created this relationship and the lessons tobacco
      control advocates can learn from the industry's example, in order to mitigate
      possible unintended consequences of advocating excise tax increases. In 1998,
      under the terms of the Master Settlement Agreement, the tobacco industry began
      making documents produced in litigation available publicly. Currently,
      approximately 50 million pages are available online, including substantial
      documentation of the industry-CLUW relationship. For this study, a comprehensive
      search of these documents was conducted. The tobacco industry encouraged CLUW's
      opposition to excise tax increases by emphasizing the economic regressivity of
      these taxes, discussing excise taxes generically to deflect attention from
      cigarettes, and encouraging opposition to earmarking cigarette taxes to pay for
      specific programs. In addition, CLUW received at least $221,500 in financial
      support between 1987 and 1997 and in-kind support for its conferences, membership
      materials, and other services. Excise tax increases, if pursued without
      considering the impacts they may have on low-SES populations, may have unintended
      consequences. In this case, such proposals may have helped to create a
      relationship between CLUW and the tobacco industry. Because excise taxes are
      endorsed in the Framework Convention on Tobacco Control, tobacco-control
      advocates must understand how to build relationships with low-SES populations and
      mitigate potential alliances with the tobacco industry.

PMID- 19591751
TI  - Did cigarette vouchers increase female smokers in China?
AB  - BACKGROUND: From 1960 to 1980, a voucher was required to purchase cigarettes in
      China. The Chinese government issued vouchers to ration cigarettes, without
      informing its citizens that smoking was unhealthy. These vouchers were available
      to all adults, and allowed them to purchase specified numbers of cigarettes. As a
      result, a number of nonsmokers started smoking during the voucher period.
      METHODS: This study included 229 female and 1165 male smokers from the China
      Health and Nutrition Survey 1989-2006, which provides the year in which each
      respondent began smoking. The percentages of male and female smokers who started
      smoking during the voucher period were compared using the chi-square test.
      Logistic regression analysis was used to study the relative risk of smoking
      initiation by women during the voucher period, while adjusting for confounding
      variables. RESULTS: During the voucher period, 46% of female smokers and 39% of
      male smokers started smoking (p=0.05). Women who did not have a regular job or
      were less educated were more likely to start smoking. The relative risk of female
      smokers to have initiated smoking during the voucher period was 4.75, with a
      p<0.01 in the logistic regression. CONCLUSIONS: China's policy of issuing
      vouchers to ration tobacco consumption had the unintended consequence of
      encouraging smoking, particularly among women. Issuing cigarette vouchers to
      every adult, combined with the inexpensive prices of cigarettes, led more women
      to initiate smoking. Women with low SES were particularly likely to initiate
      smoking.

PMID- 19591752
TI  - Sex, gender, and secondhand smoke policies: implications for disadvantaged women.
AB  - CONTEXT: Although implementation of secondhand smoke policies is increasing,
      little research has examined the unintended consequences of these policies for
      disadvantaged women. EVIDENCE ACQUISITION: Macro-, meso-, and micro-level issues
      connected to secondhand smoke and women are considered to illustrate the range of
      ways in which sex, gender, and disadvantage affect women's exposure to secondhand
      smoke. A review of current literature, primarily published between 2000 and 2008,
      on sex- and gender-based issues related to secondhand smoke exposure and the
      effects of secondhand smoke policies for various subpopulations of women,
      including low-income girls and women, nonwhite minority women, and pregnant
      women, was conducted in 2008. These materials were critically analyzed using a
      sex and gender analysis, allowing for the drawing of inferences and reflections
      on the unintended effects of secondhand smoke policies on disadvantaged women.
      EVIDENCE SYNTHESIS: Smoke-free policies do not always have equal or even desired
      effects on low-income girls and women. Low-income women are more likely to be
      exposed to secondhand smoke, may have limited capacity to manage their exposure
      to secondhand smoke both at home and in the workplace, and may experience
      heightened stigmatization as a result of secondhand smoke policies. CONCLUSIONS:
      Various sex- and gender-related factors, such as gendered roles, unequal power
      differences between men and women, child-caring roles, and unequal earning power,
      affect exposure and responses to secondhand smoke, women's capacity to control
      exposure, and their responses to protective policies. In sum, a much more nuanced
      gender- and diversity-sensitive framework is needed to develop research and
      tobacco control policies that address these issues.

PMID- 19591753
TI  - Unintended consequences of smoke-free bar policies for low-SES women in three
      California counties.
AB  - BACKGROUND: To amplify earlier studies of unintended consequences of public
      policies, this article illustrates both negative and positive unanticipated
      consequences of smoke-free workplace policies in California bars for women of low
      SES. METHODS: The article relies on thematic analysis in 2008 of qualitative data
      gathered between 2001 and 2007 from three mixed-method studies of tobacco use in
      and around bars where indoor smoking is prohibited. RESULTS: Unanticipated
      consequences primarily occurred when bars did comply with the law and smokers
      went outside the bar to smoke, particularly when smokers stood on the street
      outside the bar. Key negative consequences for women who smoked outside of bars
      included threats to their physical safety and their public image. For women
      living near bars, increased smoking on the street may have increased their
      exposure to secondhand smoke and disruptive noise. For some women, however,
      unanticipated negative consequences were identified with noncompliant bars.
      Smokers were conjectured to congregate in the smaller number of bars where
      smoking was still allowed, resulting in increased exposure to secondhand smoke
      for low-SES women working in these bars. A common positive unintended consequence
      of the tobacco control ordinance was increased social circulation and solidarity,
      as smokers gathered outside bars to smoke. CONCLUSIONS: Smoke-free workplace laws
      in bars can have both negative and positive consequences for workers and smokers,
      and low-income women in particular.

PMID- 19591754
TI  - Smoke-free policies among Asian-American women: comparisons by education status.
AB  - BACKGROUND: California has significantly decreased racial/ethnic and educational
      disparities in smoke-free home and indoor work policies. California's ethnic
      specific surveys present an opportunity to disaggregate data and examine the
      impact of California's smoke-free social norm campaign for Asian-American women.
      METHODS: The California Tobacco Use Surveys for Chinese Americans and Korean
      Americans were conducted in 2003 and analyzed in 2008 to compare women with lower
      (<or= high school graduate) or higher education status for smoke-free policy
      adoption and enforcement. RESULTS: Lower-educated and higher-educated women had
      similar proportions of smoke-free policies at home (58%) or indoor work (90%).
      However, lower-educated women were more likely than higher-educated women to
      report anyone ever smoking at home (OR=1.62, 95% CI=1.06, 2.48, p=0.03) and
      exposure during the past 2 weeks at an indoor workplace (OR=2.43, 95% CI= 1.30,
      4.55, p=0.005), even after controlling for ethnicity, smoke-free policy,
      knowledge about the health consequences of secondhand smoke exposure, and
      acculturation. There was no interaction between education and knowledge about
      secondhand smoke health harms. CONCLUSIONS: The intended consequences of
      California's tobacco-control efforts have resulted in similar rates of smoke-free
      policies at home and in indoor work environments among Asian-American women
      across educational levels. However, an unintended consequence of this success is
      a disparity in enforcement by educational status, with lower-educated Asian
      American women reporting greater smoke exposure despite similar rates of
      knowledge about the health consequences of secondhand smoke exposure. Besides
      establishing policies, lower-educated Asian-American women may need to be
      empowered to assert and enforce their right to smoke-free environments.

PMID- 19591755
TI  - Potential unintended consequences of tobacco-control policies on mothers who
      smoke: a review of the literature.
AB  - BACKGROUND: Secondhand smoke poses risks to children, particularly those from low
      socioeconomic backgrounds. Recently, there has been an increase in tobacco
      control policies designed to reduce children's exposure to secondhand smoke,
      including interventions to change parental smoking behaviors. However, little
      attention has been paid to understanding potential unintended consequences of
      such initiatives on mothers who smoke. As such, the objectives of this paper are
      to explore the potential consequences of tobacco-control policies designed to
      reduce children's exposure to secondhand smoke on socially disadvantaged mothers
      who smoke and to provide recommendations for research, policy, and practice.
      EVIDENCE ACQUISITION: A theory-guided, qualitative narrative review of the
      perceived discrimination, stigma, and stress and coping literature was conducted.
      MEDLINE and PsycINFO were searched to identify relevant articles from 1980 to
      October 2008 for review. EVIDENCE SYNTHESIS: There is evidence that strategies
      designed to reduce secondhand smoke have contributed to smoking stigmatization.
      However, there is little research on the consequences of these initiatives or how
      they affect low-income mothers who smoke. Stigmatization research suggests that
      such policies may have unanticipated outcomes for socially disadvantaged mothers
      who smoke, such as decreased mental health; increased use of cigarettes or
      alcohol; avoidance or delay in seeking medical care; and poorer treatment by
      healthcare professionals. Recommendations for researchers, practitioners, and
      policymakers are presented. CONCLUSIONS: Further research is needed to understand
      how initiatives to reduce children's exposure to secondhand smoke, as well as
      broader tobacco-control initiatives, can be designed to minimize potential harm
      to mothers who smoke.

PMID- 19591756
TI  - Potential unintended consequences of smoke-free policies in public places on
      pregnant women in China.
AB  - BACKGROUND: Smoke-free policies in public places have become more common in
      China. Little is known, however, about the potential unintended consequences of
      such policies on pregnant women. METHODS: The study was conducted in 2006 in
      Chengdu, China. Nonsmoking pregnant women (N=55) whose husband were smokers
      participated in a study of their knowledge about secondhand smoke and smoke-free
      policies, their exposure to secondhand smoke, and their husbands' smoking status
      at home. This study presents descriptive statistics, analyses based on family
      income and pregnant women's education level, and the findings of focus group
      discussions that examined the potential unintended consequences of the smoke-free
      policies on pregnant women. RESULTS: Exposure to secondhand smoke at home was
      reported by 69.1% of the pregnant women. Both family income and the education
      level of the pregnant women had a significant (p<0.05) association with exposure
      to secondhand smoke. The four main potential unintended consequences of the smoke
      free policies were: (1) increased exposure of pregnant women to secondhand smoke
      at home; (2) reduced work efficiency; (3) adverse effect on family harmony; and
      (4) poor air quality at home. CONCLUSIONS: Education is needed to increase
      knowledge of secondhand smoke among smokers and nonsmokers alike. When the
      smoking location is shifted from public places and workplaces to home, women, and
      in particular pregnant women, become the victims. Policymakers should recognize
      such potential unintended consequences and take necessary measures to increase
      awareness about the harms of secondhand smoke.

PMID- 19591757
TI  - Do you need to smoke to get a break?: smoking status and missed work breaks among
      staff nurses.
AB  - INTRODUCTION: The prevalence of missed work breaks by smoking status in
      healthcare settings is unknown. The work routines of nurses (Registered Nurses
      [RNs] and Licensed Practical Nurses [LPNs]), who smoke at higher rates than other
      health professionals, may be influenced by smokers who use breaks to avoid
      nicotine withdrawal. The purpose of this study was to examine the relationship
      between nurses' smoking status and work breaks and to explore the relationships
      among personal, professional, and workplace variables associated with missed work
      breaks. METHODS: A web-based survey of 2589 staff nurses from 34 hospitals was
      conducted in 2006. Each hospital had been designated as a Magnet hospital by the
      American Nurses Credentialing Center. Data analysis included descriptive
      statistics, chi-square tests, and multivariate logistic regression. RESULTS: The
      majority (90%) were nonsmokers; 97% were RNs. Missed breaks were common (70%) and
      differed by smoking status: 59% of smokers and 72% of nonsmokers frequently
      missed work breaks. Multivariate logistic regression determined that nonsmokers
      (OR=1.81, 95% CI=1.36, 2.42), LPNs (OR=2.37, 95% CI=1.16, 4.84), older nurses (OR
      1.02, 95% CI=1.01, 1.03), those in emergency rooms (OR=1.75, 95% CI=1.25, 2.47),
      and in intensive care units (OR=1.60, 95% CI=1.22, 2.09) were more likely to miss
      breaks. CONCLUSIONS: Missed work breaks were common among nurses. Those who did
      not smoke were almost twice as likely to miss their work breaks as compared to
      smokers. Inequities in breaks, especially by smoking status, may cause dissension
      in the workplace and negatively affect patient care. Policies that support work
      breaks for all nurses are needed.

PMID- 19591758
TI  - Maternal tobacco use and shorter newborn nursery stays.
AB  - OBJECTIVE: Nationally, 10%-15% of women report smoking during the last 3 months
      of pregnancy. Because the Joint Commission on Accreditation of Healthcare
      Organizations (now the Joint Commission) requires all U.S. hospitals to be smoke
      free, and because tobacco is addictive, the maternal desire to smoke after
      childbirth could lead to requests for early hospital discharge for mothers and
      newborns. The authors hypothesized that maternal tobacco use would be associated
      with shorter newborn nursery hospital stays. METHODS: Birth records from 405,622
      singleton, "well" newborns, >or=35 weeks gestation born from 1998 to 2002 in
      Pennsylvania were merged with perinatal hospital record data and analyzed from
      2006 to 2008. Perinatal data from 67,145 mothers self-reporting as having smoked
      cigarettes on the Certificate of Live Birth and data on their infants were
      compared 1:2 with data from mothers reporting to be nonsmokers and their infants
      via chi-square tests with odds ratios, 2-sample t-tests, and multiple linear
      regression. RESULTS: In Pennsylvania, 16.6% of mothers smoked cigarettes during
      pregnancy. Tobacco-using mothers were more likely to be insured by Medicaid,
      unmarried, adolescent, not college educated, and have late onset of prenatal
      care. Their newborns were more likely to be low birth weight and be born at 35-36
      weeks gestation. Nonetheless, these newborns had a significantly shorter mean
      length of stay (48.9 hours vs 52.4 hours; p<0.001), even after adjusting for
      confounders. A significant inverse relationship existed between number of
      cigarettes smoked per day by mothers and nursery length of stay for newborns.
      CONCLUSIONS: Hospital smoking bans send a strong public health message regarding
      the risks of tobacco and protect patients and staff from secondhand smoke
      exposure. However, the association between maternal tobacco use and shorter
      newborn hospital stays may demonstrate an unintended consequence for the
      vulnerable population of newborns whose mothers smoke. This association should be
      considered during prenatal counseling, where smoking cessation can be emphasized,
      and at the time of mother and infant discharge. These findings are particularly
      important given the health and socioeconomic disparities between smoking mother
      infant pairs and their nonsmoking counterparts.

PMID- 19591759
TI  - Smoking bans and restrictions in U.S. prisons and jails: consequences for
      incarcerated women.

PMID- 19591760
TI  - Unintended consequences of tobacco policies: implications for public health
      practice.

PMID- 19591761
TI  - Why social disparities matter for tobacco-control policy.

PMID- 19591763
TI  - Abdominal manifestations of systemic lupus erythematosus: spectrum of imaging
      findings.
AB  - Systemic lupus erythematosus is an immune-mediated syndrome in which the immune
      response is to non-organ-specific antigens, and virtually every organ in the
      abdominal cavity may become involved. Only renal involvement forms part of the
      diagnostic criteria, however, a combination of typically nonspecific findings,
      including peritoneal surface, enteric, renal, renal tract, pancreatic, adrenal,
      hepatobiliary, and splenic manifestations, should be looked for in patients with
      known lupus or other connective tissue disease who are undergoing abdominal
      imaging and may suggest the diagnosis in patients presenting with an acute
      abdomen. Our work presents the spectrum of imaging findings of abdominal
      manifestations of systemic lupus erythematosus.

PMID- 19591762
TI  - Is magnetic resonance imaging a suitable imaging modality for the diagnosis of
      osteomyelitis of the foot or ankle?

PMID- 19591764
TI  - MRA: Current applications in body vascular imaging.

PMID- 19591765
TI  - Answer to case of the month #149 alveolar soft-part sarcoma.

PMID- 19591766
TI  - Answer to case of the month #150 right iliac fossa abscess secondary to cecal
      perforation by toothpick.

PMID- 19591767
TI  - Answer to Case of the Month #151 Lemierre's syndrome.

PMID- 19591768
TI  - Answer to case of the month #152 retroperitoneal teratoma.

PMID- 19591773
TI  - Hippocampus abdominalis.

PMID- 19591774
TI  - Tailoring cancer treatment using germline cancer genetics - are we almost there?

PMID- 19591775
TI  - Tetrahedron Young Investigator Award 2009: Carlos F. Barbas, III.

PMID- 19591777
TI  - Assessment of disease activity and quality of life in systemic lupus
      erythematosus - New aspects.
AB  - Outcomes in systemic lupus erythematosus (SLE) can be described in three domains:
      disease activity, accumulated damage and health-related quality of life (HRQoL).
      Over the past decade, our understanding and perception of SLE have changed
      considerably. Gastrointestinal and ophthalmic manifestations have increasingly
      been recognised, and they are associated with significant morbidity and
      mortality. Furthermore, it has been realised that there is a deficiency in using
      generic scales (such as the short form-36 (SF-36)) to assess HRQoL in patients
      with SLE as they fail to identify issues that are important to patients. As a
      result, SLE-specific measures of HRQoL have been developed recently. This article
      looks at the recent updates and changes in the standardised assessment of disease
      activity and HRQoL in SLE.

PMID- 19591778
TI  - Respiratory manifestations of systemic lupus erythematosus: old and new concepts.
AB  - The respiratory system is commonly involved in systemic lupus erythematosus. Lung
      disorders are classified as primary (due to lupus) and secondary to other
      conditions. Pleuritis and pulmonary infections are the most prevalent respiratory
      manifestations of each type. Other infrequent manifestations include interstitial
      lung disease, acute lupus pneumonitis, diffuse alveolar haemorrhage, pulmonary
      arterial hypertension, acute reversible hypoxaemia and shrinking lung syndrome.
      Even when current diagnostic tests contribute to an earlier diagnosis, the
      treatment of these manifestations is based on clinical experience and small
      series. Larger controlled trials of the different therapies in the treatment of
      those lung manifestations of lupus are needed. Overall malignancy is little
      increased in lupus, but lung cancer and non-Hodgkin's lymphoma are among the most
      frequent types of cancer found in these patients. As survival in lupus patients
      has improved over recent decades, avoiding pulmonary damage emerges as an
      important objective.

PMID- 19591779
TI  - Cardiovascular risk assessment and treatment in systemic lupus erythematosus.
AB  - With improved treatment modalities and survival rates, patients with systemic
      lupus erythematosus live longer and their co-morbidities have become more
      apparent. Of great concern is cardiovascular disease, which has become a leading
      cause of death. Lupus patients prematurely develop atherosclerosis, which likely
      arises from an interaction among traditional cardiovascular risk factors, factors
      specific to lupus itself and inflammatory mediators. Despite these findings,
      lupus patients are not always adequately evaluated for traditional risk factors,
      many of which are treatable and reversible. We propose that lupus patients be
      assessed and managed regarding cardiovascular risk factors in the same manner as
      patients with known cardiovascular disease. As a result, preventive cardiology
      should be considered an essential component of the care for patients with lupus.

PMID- 19591780
TI  - Lupus arthritis.
AB  - Arthritis in systemic lupus erythematosus (SLE) is one of the most common disease
      manifestations. Nearly all joints can be affected by SLE, but hand and knee
      involvement are the most typical. Periarticular structures can be inflamed
      leading to tendonitis, tenosynovitis and tendon rupture. Avascular necrosis (AVN)
      also occurs causing joint pain and disability, typically in larger joints such as
      the hip and knee. This article addresses the clinical features of arthritis in
      lupus and an approach to the differential diagnosis. Treatment strategies include
      nonsteroidal anti-inflammatories, corticosteroids, anti-malarials and a variety
      of immunosuppressive medications.

PMID- 19591782
TI  - How to manage patients with systemic lupus erythematosus who are also
      antiphospholipid antibody positive.
AB  - Between 20% and 40% of patients with systemic lupus erythematosus (SLE) have
      positive blood tests for antiphospholipid antibodies (aPLs). This article
      explains what tests are used to detect these antibodies and outlines the
      complexities of interpreting and acting upon a positive result. If aPLs are
      persistently positive, the patient may develop antiphospholipid syndrome (APS)
      characterised by vascular thrombosis, pregnancy morbidity or both. In patients
      with SLE who are aPL-positive but have not developed APS, there is some evidence
      that low-dose aspirin should be used prophylactically, but it is not conclusive.
      APS in patients with SLE is clinically similar to primary APS and should be
      treated in the same way, with anticoagulation to prevent recurrent thrombosis or
      with aspirin and sometimes heparin to prevent pregnancy loss. Current best
      practice in use of these treatments is discussed. However, these treatments are
      not ideal as they can have major side effects such as haemorrhage. Research which
      may lead to better, more targeted therapy for APS is discussed at the end of the
      article.

PMID- 19591784
TI  - Challenges of ethnicity in SLE.
AB  - Systemic lupus erythematosus (SLE) is associated with significant morbidity and
      mortality and has a huge impact on patients' well-being. The disease occurs
      worldwide and is particularly common in patients of African descent in Europe and
      North America and in those of Asian origin. Patients often require therapies for
      prolonged periods of time. The outcome of the disease is dependent on early
      diagnosis and treatment, and, most importantly, patients' willingness to accept
      the diagnosis and the need to adhere to advice about therapy. It is important to
      understand patients' beliefs and perceptions about the disease and its therapy,
      which are influenced by their ethnic background, as this is likely to influence
      adherence and outcome. Further research is required to identify the best
      approaches to improve patients' understanding about lupus and its treatments and
      to show that improving adherence does indeed improve long-term outcomes.

PMID- 19591781
TI  - The search for lupus biomarkers.
AB  - Few biomarkers for systemic lupus erythematosus (SLE) have been validated and
      employed for making clinical decisions. The lack of reliable, specific biomarkers
      for SLE hampers the proper clinical management of patients with SLE and impedes
      the development of new lupus therapeutics. This void has led to renewed
      enthusiasm for identifying biomarkers that precisely and specifically reflect the
      pathophysiological and clinical changes of SLE. Several laboratory markers have
      shown early promise as biomarkers for lupus susceptibility, diagnosis and
      monitoring. These include polymorphisms and copy-number variations of complement
      C4 and Fcgamma receptor genes (disease susceptibility), cell-bound complement C4d
      (diagnosis and/or disease activity), CD27(high) plasma cells (disease activity),
      'interferon signature' (disease activity) and anti-C1q and anti-NMDA (disease
      activity and organ involvement). Although these and other promising candidate
      biomarkers have been identified, they still need to be validated through
      rigorous, large-scale multicentre studies. This article briefly reviews the
      historical aspects of lupus biomarkers and summarises current efforts to advance
      the field.

PMID- 19591785
TI  - Treating lupus: from serendipity to sense, the rise of the new biologicals and
      other emerging therapies.
AB  - During the last 10 years our increasing understanding of the immunopathogenesis
      of systemic lupus erythematosus (SLE) has led to the introduction of several new
      biological therapies. SLE treatment has moved from the use of conventional drugs
      such as hydroxychloroquine, corticosteroids, and non-specific immunosuppressants
      to targeting selective components of the immune system in the hope that they can
      be more effective and reduce undesired side-effects. These new treatments include
      B-cell-depleting therapies, antibodies and fusion proteins that block
      interleukins or the cross-talk between B and T cells, and tolerogens. However,
      although there are great expectations about new agents, double-blind controlled
      trials demonstrating safety and efficacy are still awaited, and better
      instruments for evaluating disease activity need to be developed.

PMID- 19591783
TI  - Malignancy in systemic lupus erythematosus: what have we learned?
AB  - What have we learnt about cancer risk in systemic lupus erythematosus (SLE) over
      the past decade? One important lesson is that data do confirm a slightly
      increased risk in SLE for all cancers combined, compared to that in the general
      population. However, it is clear that this is largely driven by an increased risk
      for haematological malignancies, particularly non-Hodgkin's lymphoma (NHL),
      although Hodgkin's lymphoma may be increased as well. In addition, there is
      evidence for a moderately increased risk of lung cancer, and possibly for rarer
      cancer types such as hepatobiliary and vulvar/vaginal malignancies.
      Unfortunately, the most clinically relevant question--the mechanism underlying
      the association between cancer and SLE--remains largely unanswered. Key issues
      remaining relate to the links between cancer risk, SLE disease activity, and
      medication exposures. Much of the recent data suggest that disease-related
      factors may be at least as important as medication exposures for certain cancers,
      such as NHL. The independent effects of drug exposures versus disease activity in
      mediating cancer risk in SLE remain unknown. Work is in progress to further
      elucidate these important issues. Meanwhile, there is good evidence that cervical
      dysplasia is increased in women with SLE. This may be mediated by decreased
      clearance of the human papilloma virus, which some suggest is an innate
      characteristic of SLE patients. However, an increased risk of cervical dysplasia
      is also associated with immunosuppressive medication exposures, particularly
      cyclophosphamide. For these reasons, it is important that women with SLE follow
      established guidelines for cervical cancer screening.

PMID- 19591786
TI  - Managing lupus patients during pregnancy.
AB  - Pregnancy still constitutes a major challenge for women with systemic lupus
      erythematosus. Coordinated medical/obstetric care is essential to maximise the
      chance of success. Pregnancy should be planned in advance, following a pre
      conceptional visit in which the specific risk for complications can be assessed.
      Previous complicated pregnancies, renal disease, irreversible damage, anti
      phospholipid antibodies and treatment with high-dose steroids are adverse
      features. Pregnancy should be discouraged in women with symptomatic pulmonary
      hypertension, heart failure, severe restrictive pulmonary disease, severe chronic
      renal failure and recent serious lupus activity. Treatment is based on
      hydroxychloroquine, low-dose steroids, azathioprine and in patients with anti
      phospholipid antibodies, low-dose aspirin+/-low molecular weight heparin. Close
      surveillance, with monitoring of blood pressure, proteinuria and placental blood
      flow by Doppler studies helps the early diagnosis and treatment of complications
      such as pre-eclampsia and foetal distress. Post-partum follow-up is also
      essential.

PMID- 19591787
TI  - In-depth cDNA library sequencing provides quantitative gene expression profiling
      in cancer biomarker discovery.
AB  - Quantitative gene expression analysis plays an important role in identifying
      differentially expressed genes in various pathological states, gene expression
      regulation and co-regulation, shedding light on gene functions. Although
      microarray is widely used as a powerful tool in this regard, it is suboptimal
      quantitatively and unable to detect unknown gene variants. Here we demonstrated
      effective detection of differential expression and co-regulation of certain genes
      by expressed sequence tag analysis using a selected subset of cDNA libraries. We
      discussed the issues of sequencing depth and library preparation, and propose
      that increased sequencing depth and improved preparation procedures may allow
      detection of many expression features for less abundant gene variants. With the
      reduction of sequencing cost and the emerging of new generation sequencing
      technology, in-depth sequencing of cDNA pools or libraries may represent a better
      and powerful tool in gene expression profiling and cancer biomarker detection. We
      also propose using sequence-specific subtraction to remove hundreds of the most
      abundant housekeeping genes to increase sequencing depth without affecting
      relative expression ratio of other genes, as transcripts from as few as 300 most
      abundantly expressed genes constitute about 20% of the total transcriptome. In
      depth sequencing also represents a unique advantage of detecting unknown forms of
      transcripts, such as alternative splicing variants, fusion genes, and regulatory
      RNAs, as well as detecting mutations and polymorphisms that may play important
      roles in disease pathogenesis.

PMID- 19591788
TI  - DNA copy number aberrations in breast cancer by array comparative genomic
      hybridization.
AB  - Array comparative genomic hybridization (CGH) has been popularly used for
      analyzing DNA copy number variations in diseases like cancer. In this study, we
      investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb
      resolution bacterial artificial chromosome CGH arrays. A number of highly
      frequent genomic aberrations were discovered, which may act as "drivers" of tumor
      progression. Meanwhile, the genomic profiles of four "normal" breast tissue
      samples taken at least 2 cm away from the primary tumor sites were also found to
      have some genomic aberrations that recurred with high frequency in the primary
      tumors, which may have important implications for clinical therapy. Additionally,
      we performed class comparison and class prediction for various
      clinicopathological parameters, and a list of characteristic genomic aberrations
      associated with different clinicopathological phenotypes was compiled. Our study
      provides clues for further investigations of the underlying mechanisms of breast
      carcinogenesis.

PMID- 19591790
TI  - Bioinformatic comparison of bacterial secretomes.
AB  - The rapid increasing number of completed bacterial genomes provides a good
      opportunity to compare their proteomes. This study was undertaken to specifically
      compare and contrast their secretomes-the fraction of the proteome with predicted
      N-terminal signal sequences, both type I and type II. A total of 176 theoretical
      bacterial proteomes were examined using the ExProt program. Compared with the
      Gram-positives, the Gram-negative bacteria were found, on average, to contain a
      larger number of potential Sec-dependent sequences. In the Gram-negative bacteria
      but not in the others, there was a positive correlation between proteome size and
      secretome size, while there was no correlation between secretome size and
      pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were
      found to have the smallest secretomes. However, the secretomes of certain
      bacteria did not fit into the observed pattern. Specifically, the secretome of
      Borrelia burgdoferi has an unusually large number of putative lipoproteins, and
      the signal peptides of mycoplasmas show closer sequence similarity to those of
      the Gram-negative bacteria. Our analysis also suggests that even for a
      theoretical minimal genome of 300 open reading frames, a fraction of this gene
      pool (up to a maximum of 20%) may code for proteins with Sec-dependent signal
      sequences.

PMID- 19591789
TI  - Comparative analysis of protein-protein interactions in cancer-associated genes.
AB  - Protein-protein interactions (PPIs) have been widely studied to understand the
      biological processes or molecular functions associated with different disease
      systems like cancer. While focused studies on individual cancers have generated
      valuable information, global and comparative analysis of datasets from different
      cancer types has not been done. In this work, we carried out bioinformatic
      analysis of PPIs corresponding to differentially expressed genes from microarrays
      of various tumor tissues (belonging to bladder, colon, kidney and thyroid
      cancers) and compared their associated biological processes and molecular
      functions (based on Gene Ontology terms). We identified a set of processes or
      functions that are common to all these cancers, as well as those that are
      specific to only one or partial cancer types. Similarly, protein interaction
      networks in nucleic acid metabolism were compared to identify the common/specific
      clusters of proteins across different cancer types. Our results provide a basis
      for further experimental investigations to study protein interaction networks
      associated with cancer. The methodology developed in this work can also be
      applied to study similar disease systems.

PMID- 19591791
TI  - Role of positive selection pressure on the evolution of H5N1 hemagglutinin.
AB  - The surface glycoprotein hemagglutinin (HA) helps the influenza A virus to evade
      the host immune system by antigenic variation and is a major driving force for
      viral evolution. In this study, the selection pressure on HA of H5N1 influenza A
      virus was analyzed using bioinformatics algorithms. Most of the identified
      positive selection (PS) sites were found to be within or adjacent to epitope
      sites. Some of the identified PS sites are consistent with previous experimental
      studies, providing further support to the biological significance of our
      findings. The highest frequency of PS sites was observed in recent strains
      isolated during 2005-2007. Phylogenetic analysis was also conducted on HA
      sequences from various hosts. Viral drift is almost similar in both avian and
      human species with a progressive trend over the years. Our study reports new
      mutations in functional regions of HA that might provide markers for vaccine
      design or can be used to predict isolates of pandemic potential.

PMID- 19591792
TI  - Phylogenetic analysis of the neuraminidase gene reveals that the H5N1 strains
      prevalent in chickens during 2006 bird flu outbreaks in two regions of
      Maharashtra, India are genetically different.
AB  - In February 2006, two outbreaks of highly pathogenic avian influenza A virus
      subtype H5N1 occurred in chickens in two neighboring districts (first in
      Nandurbar and second in Jalgaon) of Maharashtra, India, in a span of 12 days. In
      the present study, the neuraminidase (NA) gene of the two Indian H5N1 isolates
      was taken into consideration to find if the two strains are genetically similar.
      Phylogenetic analysis of the NA gene showed that the H5N1 strains isolated from
      the two outbreaks were not originated from the same source. The first Indian
      isolate (Nandubar/7972/06) was clustered closest to an isolate from chicken in
      Vietnam in 2004, whereas the second Indian isolate (Jalgaon/8824/06) showed
      resemblance to strains isolated from swan in Italy and Iran in 2006. Moreover,
      amino acid sequence analysis showed varying hot spots for substitutions between
      these two Indian isolates, and three substitutions were found at functional
      domain sites. Secondary structure changes due to these substitutions were also
      reported. This study reveals that the H5N1 strains isolated from chickens during
      2006 bird flu outbreaks in two neighboring districts of Maharashtra, India are
      genetically different.

PMID- 19591793
TI  - A method for identification of selenoprotein genes in archaeal genomes.
AB  - The genetic codon UGA has a dual function: serving as a terminator and encoding
      selenocysteine. However, most popular gene annotation programs only take it as a
      stop signal, resulting in misannotation or completely missing selenoprotein
      genes. We developed a computational method named Asec-Prediction that is specific
      for the prediction of archaeal selenoprotein genes. To evaluate its
      effectiveness, we first applied it to 14 archaeal genomes with previously known
      selenoprotein genes, and Asec-Prediction identified all reported selenoprotein
      genes without redundant results. When we applied it to 12 archaeal genomes that
      had not been researched for selenoprotein genes, Asec-Prediction detected a novel
      selenoprotein gene in Methanosarcina acetivorans. Further evidence was also
      collected to support that the predicted gene should be a real selenoprotein gene.
      The result shows that Asec-Prediction is effective for the prediction of archaeal
      selenoprotein genes.

PMID- 19591794
TI  - GALT protein database, a bioinformatics resource for the management and analysis
      of structural features of a galactosemia-related protein and its mutants.
AB  - We describe the GALT-Prot database and its related web-based application that
      have been developed to collect information about the structural and functional
      effects of mutations on the human enzyme galactose-1-phosphate uridyltransferase
      (GALT) involved in the genetic disease named galactosemia type I. Besides a list
      of missense mutations at gene and protein sequence levels, GALT-Prot reports the
      analysis results of mutant GALT structures. In addition to the structural
      information about the wild-type enzyme, the database also includes structures of
      over 100 single point mutants simulated by means of a computational procedure,
      and the analysis to each mutant was made with several bioinformatics programs in
      order to investigate the effect of the mutations. The web-based interface allows
      querying of the database, and several links are also provided in order to
      guarantee a high integration with other resources already present on the web.
      Moreover, the architecture of the database and the web application is flexible
      and can be easily adapted to store data related to other proteins with point
      mutations. GALT-Prot is freely available at
      http://bioinformatica.isa.cnr.it/GALT/.

PMID- 19591797
TI  - Overcoming innate host resistance to vaccination: employing a genetically
      distinct strain of murine cytomegalovirus avoids vector-mediated resistance to
      virally vectored immunocontraception.
AB  - The laboratory strain of murine cytomegalovirus (MCMV), K181, has been
      successfully engineered as a vaccine expressing murine zona pellucida 3 (mZP3)
      for viral vectored immunocontraception (VVIC) in mice. However, certain
      laboratory strains of mice are resistant to infection with K181 and therefore
      demonstrate resistance to VVIC. Cmv1 is the best characterised innate resistance
      mechanism to MCMV and was first described in C57BL/6 mice. Resistance in C57BL/6
      mice is due to early and strong activation of natural killer (NK) cells by an
      MCMV gene product, m157, that binds directly to the NK cell activating receptor
      Ly49H. In this study a wild strain of MCMV, G4, which expresses a variant m157
      incapable of activating Ly49H, was engineered to express murine zona pellucida 3
      (mZP3) and assessed for its ability to sterilise female C57BL/6 mice. When
      infected with K181-mZP3 female C57BL/6 mice remained fully fertile. In contrast,
      female C57BL/6 mice were sterilised by a single intraperitoneal inoculation of G4
      mZP3. Infertility was induced by G4-mZP3 in three strains of mice that express
      Ly49H, on two different histocompatibility-2 (H-2) backgrounds. Finally, enhanced
      immunocontraception was observed in mice expressing H-2(k) mediated resistance to
      MCMV when infected with G4-mZP3 compared to K181-mZP3. These data indicate that
      when using viral vaccine vectors, variant vector strains may be used to
      circumvent powerful innate immune responses against the vector and promote
      effective vaccination. This study highlights the importance of vaccine vector
      genetics in vaccination strategies.

PMID- 19591795
TI  - Plasmodium falciparum apical membrane antigen 1 vaccine elicits multifunctional
      CD4 cytokine-producing and memory T cells.
AB  - The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading vaccine
      candidate and was tested for safety and immunogenicity in human Phase I Clinical
      Trials. PBMC from vaccine recipients were analyzed by flow cytometric methods to
      determine the nature of T-cell responses and AMA1-reactive memory T cells. Both
      CD4 and CD8 T cells produced a number of cytokines following AMA1 re-stimulation,
      with IL-5-producing cells at the highest frequency, consistent with a Th2 bias.
      The relative frequency of multifunctional cells synthesizing Th1 cytokines IFN
      gamma, IL-2 and TNF-alpha changed after each vaccination. Interestingly, median
      fluorescence intensity measurements revealed that cells producing more than one
      cytokine contributed greater quantities of each cytokine than cell populations
      that produced each of the cytokines alone. AMA1 vaccination also elicited the
      development of memory cell populations, and both central and effector memory T
      cells were identified concurrently after the AMA1 vaccination. The detailed
      profile of multifunctional T-cell responses to AMA1 presented here will advance
      our ability to assess the immunogenicity of human malarial vaccines.

PMID- 19591798
TI  - Photochemical approaches for bonding of cartilage tissues.
AB  - OBJECTIVE: The objective of this study was to evaluate photochemical bonding as
      an approach for adhering live cartilage tissues across a repair interface in a
      manner that may lead to enhanced integration. DESIGN: Photochemical bonding of
      both meniscal fibrocartilage and articular cartilage was explored using an
      anionic, hydrophilic phthalocyanine photosensitizer. Variations on surface
      preparations and irradiation parameters were explored using overlapped tissue
      strips and tested using a modified single-lap shear test. Durability of the
      photochemically induced bonds and cellular viability were examined in an in vitro
      cartilage defect model for up to 1 week in culture, with bond strength assessed
      via push-out test. RESULTS: Meniscal tissue strips bonded with no surface
      treatment, but cartilage strips required enzymatic treatment with chondroitinase
      ABC to effectively bond. More aggressive removal of glycosaminoglycans at the
      interface led to increased bond strengths. Bond strength achieved with a 10min
      irradiation of treated tissue was on the order of that previously achieved
      through several weeks of culture. In the defect model, photochemical bonds
      between a tissue annulus and a press-fit tissue core were maintained for 1 week
      in culture without substantial increases in cell death near the bonded interface.
      CONCLUSIONS: With appropriate treatment parameters, photochemical bonding rapidly
      produced a stable structural interface between cartilage tissue samples and may
      be a promising strategy for enhancing initial attachment in cartilage repair
      strategies.

PMID- 19591796
TI  - Potential population health outcomes and expenditures of HIV vaccination
      strategies in the United States.
AB  - Estimating the potential health benefits and expenditures of a partially
      effective HIV vaccine is an important consideration in the debate about whether
      HIV vaccine research should continue. We developed an epidemic model to estimate
      HIV prevalence, new infections, and the cost-effectiveness of vaccination
      strategies in the U.S. Vaccines with modest efficacy could prevent 300,000
      700,000 HIV infections and save $30 billion in healthcare expenditures over 20
      years. Targeted vaccination of high-risk individuals is economically efficient,
      but difficulty in reaching these groups may mitigate these benefits. Universal
      vaccination is cost-effective for vaccines with 50% efficacy and price similar to
      other infectious disease vaccines.

PMID- 19591799
TI  - Phylogeography of Androctonus species (Scorpiones: Buthidae) in Tunisia:
      Diagnostic characters for linking species to scorpionism.
AB  - A fragment of the mitochondrial (mt) 16S ribosomal RNA gene was amplified by PCR
      and sequenced from individual adult scorpions of the genus Androctonus, which
      were sampled from central and southern Tunisia and identified using an explicit
      set of morphological characters. Phylogenetic analyses placed the mtDNA
      haplotypes in three well-supported monophyletic lineages, corresponding to the
      morphospecies Androctonusaeneas, Androctonusamoreuxi and Androctonusaustralis.
      The latter species was the most abundant and widespread, and it was characterized
      by two mtDNA sub-lineages each of which predominated only north or south of the
      Chott el Jerid, a seasonally flooded saline depression that divides non
      Mediterranean Tunisia. The divergence of the two mtDNA lineages was dated by
      mtDNA molecular clocks, indicating that the formation of the Chott el Jerid is
      unlikely to have been the barrier generating the vicariant evolution of the two
      lineages of A. australis, although it may have impeded their mixing following
      secondary contact. Both regional mtDNA lineages were found in A. australis hector
      and A. australisgarzonii, indicating that these two morphological forms are
      neither monophyletic nor geographically isolated and, therefore, should not be
      treated as species or subspecies. It is recommended that no subspecies of A.
      australis should be recognized in North Africa and toxicologists should cease the
      taxonomic error of referring to a species "Androctonus australis Hector". The
      morphological form "hector" has no proven association with an increased risk of
      scorpionism compared with "garzonii". However, it might be prudent to produce
      anti-venom in Tunisia by using both morphological forms of A. australis collected
      each side of the Chott el Jerid, because of the evidence for regional variation
      in toxins. The highest risk for scorpion stings occurs in the central region,
      where the new diagnostic markers should be used to discover any association
      between Androctonus species and scorpionism.

PMID- 19591800
TI  - Optimization of the multiple enzymatic activities of the hepatitis C virus NS3
      protein.
AB  - The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is known to possess
      multiple enzymatic activities. In addition to its well-characterized protease
      activity, HCV NS3 also has ATP hydrolase (ATPase) and nucleic acid unwinding
      (helicase) activities. We systematically studied the effect of common reagents on
      all three enzymatic activities with a view to improving assay sensitivity for
      compound screening and profiling. Inclusion of the detergent lauryl dimethylamine
      oxide (LDAO) improves protease and helicase activities significantly, allowing
      robust assays at much lower NS3 concentrations. These conditions enable a
      particularly sensitive protease assay that uses picomolar concentrations of NS3.

PMID- 19591802
TI  - Parkin protects dopaminergic neurons from excessive Wnt/beta-catenin signaling.
AB  - Parkinson's disease (PD) is caused by degeneration of the dopaminergic (DA)
      neurons of the substantia nigra but the molecular mechanisms underlying the
      degenerative process remain elusive. Several reports suggest that cell cycle
      deregulation in post-mitotic neurons could lead to neuronal cell death. We now
      show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates beta
      catenin protein levels in vivo. Stabilization of beta-catenin in differentiated
      primary ventral midbrain neurons results in increased levels of cyclin E and
      proliferation, followed by increased levels of cleaved PARP and loss of DA
      neurons. Wnt3a signaling also causes death of post-mitotic DA neurons in parkin
      null animals, suggesting that both increased stabilization and decreased
      degradation of beta-catenin results in DA cell death. These findings demonstrate
      a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA
      neurons against excessive Wnt signaling and beta-catenin-induced cell death.

PMID- 19591801
TI  - Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell
      proliferation.
AB  - Cancer such as hepatocellular carcinoma (HCC) is characterized by complex
      perturbations in multiple signaling pathways, including the phosphoinositide-3
      kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic
      isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs
      tested against the eight known catalytic PI3K isoforms, specific ablation of
      class II PI3K alpha (PIK3C2alpha) was the most effective in impairing cell growth
      and this was accompanied by concomitant decrease in PIK3C2alpha mRNA and protein
      levels. Colony formation ability of cells deficient for PIK3C2alpha was markedly
      reduced and growth arrest was associated with increased caspase 3 levels. A small
      but significant difference in gene dosage and expression levels was detected
      between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken
      together, these data suggest for the first time that in addition to class I PI3Ks
      in cancer, class II PIK3C2alpha can modulate HCC cell growth.

PMID- 19591803
TI  - The planar cell polarity (PCP) protein Diversin translocates to the nucleus to
      interact with the transcription factor AF9.
AB  - The planar cell polarity (PCP) pathway, a beta-catenin-independent branch of the
      Wnt signaling pathway, orients cells and their appendages with respect to the
      body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego,
      acts as a molecular switch that blocks beta-catenin-dependent and promotes beta
      catenin-independent Wnt signaling. We report now that Diversin, containing
      several nuclear localization signals, translocates to the nucleus, where it
      interacts with the transcription factor AF9. Both Diversin and AF9 block
      canonical Wnt signaling; however, this occurs independently of each other, and
      does not require nuclear Diversin. In contrast, AF9 strongly augments the
      Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene
      expression in the nucleus, and this augmentation largely depends on the presence
      of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade
      translocate to the nucleus to participate in transcriptional regulation and PCP
      signaling.

PMID- 19591804
TI  - The critical iron-oxygen intermediate in human aromatase.
AB  - Aromatase (CYP19) is the target of several therapeutics used for breast cancer
      treatment and catalyzes the three-step conversion of androgens to estrogens, with
      an unusual C-C cleavage reaction in the third step. To better understand the
      CYP19 reaction, the oxy-ferrous complex of CYP19 with androstenedione substrate
      was cryotrapped, characterized by UV-vis spectroscopy, and cryoreduced to
      generate the next reaction cycle intermediate. EPR analysis revealed that the
      initial intermediate observed following cryoreduction is the unprotonated
      g(1)=2.254 peroxo-ferric intermediate, which is stable up to 180K. Upon gradual
      cryoannealing, the low-spin (g(1)=2.39) product complex is formed, with no
      evidence for accumulation of the g(1)=2.30 hydroperoxo-ferric intermediate. The
      relative stabilization of the peroxo-ferric heme and the lack of observed
      hydroperoxo-ferric heme distinguish CYP19 from other P450s, suggesting that the
      proton delivery pathway is more hindered in CYP19 than in most other P450s.

PMID- 19591805
TI  - Dimeric procyanidins are inhibitors of NF-kappaB-DNA binding.
AB  - Given the central role of the transcription factor NF-kappaB in inflammation,
      molecules that can inhibit NF-kappaB are being actively investigated. The present
      work characterize potential interactions between dimeric procyanidins [B-type (B1
      and B2) and A-type (A1 and A2)] and NF-kappaB proteins. B1 and B2, inhibited
      tumor necrosis factor alpha (TNFalpha)- and phorbol 12-myristate 13-acetate (PMA)
      induced transactivation of NF-kappaB-driven genes and the increase of NF-kappaB
      DNA nuclear binding in Jurkat T cells. B1 and B2, added in vitro to nuclear
      fractions, inhibited NF-kappaB binding to its DNA consensus sequence. B1 and B2
      prevented the binding of RelA and p50 recombinant proteins to its DNA consensus
      sequence. All these effects were not observed with A1 and A2. Putative molecular
      models for possible interactions of B1, B2, A1 and A2, with NF-kappaB proteins
      were constructed, indicating that B-type dimeric procyanidins have higher
      possibilities of chemical interactions with NF-kappaB than A-type dimeric
      procyanidins. The results support the concept that B-type dimeric procyanidins
      can provide anti-inflammatory benefits due to their ability to reduce NF-kappaB
      binding to the DNA.

PMID- 19591806
TI  - Augmentation of PPARgamma-TAZ interaction contributes to the anti-adipogenic
      activity of KR62980.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor that plays a pivotal role in the modulation of
      gene expression involved in adipocyte differentiation and insulin sensitivity. It
      has been previously established that thiazolidinedione (TZD) PPARgamma ligands
      such as rosiglitazone have potent anti-diabetic and adipogenic activities. A
      novel non-TZD ligand for PPARgamma, KR62980 has recently been characterized to
      increase insulin sensitivity and to be weakly adipogenic in 3T3-L1 cells or anti
      adipogenic in rosiglitazone-induced adipocyte differentiation. In this study, we
      have confirmed that KR62980 substantially suppresses rosiglitazone-induced
      adipocyte differentiation and attenuates adipogenic gene expression via an
      induced reduction in PPARgamma activity. KR62980 increased the nuclear
      localization of TAZ, a PPARgamma suppressor, and also enhanced the interaction
      between PPARgamma and TAZ, thus resulting in the TAZ-mediated suppression of
      PPARgamma activity. Furthermore, KR62980 failed to suppress PPARgamma-mediated
      adipogenic gene expression and adipocyte differentiation in TAZ knockdown 3T3-L1
      cells, thus indicating a TAZ-dependent suppressive activity of KR62980 on
      PPARgamma-mediated function. These findings strongly suggest that the novel
      PPARgamma ligand, KR62980, may prove to be beneficial to anti-adipogenic function
      through the suppression of PPARgamma-mediated adipocyte differentiation by
      activating TAZ.

PMID- 19591807
TI  - Involvement of Ca2+-dependent PKCs in the adaptive changes of mu-opioid pathways
      to sympathetic denervation in the guinea pig colon.
AB  - In the guinea pig colon, chronic sympathetic denervation entails supersensitivity
      to inhibitory mu-opioid agents modulating cholinergic neurons. The mechanism
      underlying such adaptive change has not yet been unravelled, although protein
      kinase C (PKC) may be involved. A previous study indirectly demonstrated that
      activation of mu-opioid receptors on myenteric neurons facilitates PKC activity.
      Such coupling may counteract the inhibitory action of mu-opioid agents on
      acetylcholine overflow, since PKC, per se, increases this parameter. After
      chronic sympathetic denervation such restraint abates, representing a possible
      mechanism for development of supersensitivity to mu-opioid agents. In the present
      study, this hypothesis was further investigated. After chronic sympathetic
      denervation, Ca(2+)-dependent PKC activity was reduced in colonic myenteric
      plexus synaptosomes. The mu-opioid agent, DAMGO, increased Ca(2+)-dependent PKC
      activity in synaptosomes obtained from normal, but not from denervated animals.
      In myenteric synaptosomes obtained from this experimental group, protein levels
      of Ca(2+)-dependent PKC isoforms betaI, betaII and gamma decreased, whereas alpha
      levels increased. In whole-mount preparations, the four Ca(2+)-dependent PKC
      isoforms co-localized with mu-opioid receptors on subpopulations of colonic
      myenteric neurons. The percentage of neurons staining for PKCbetaII, as well as
      the number of mu-opioid receptor-positive neurons staining for PKCbetaII,
      decreased in denervated preparations. The same parameters related to PKCalpha,
      betaI or gamma remained unchanged. Overall, the present data strengthen the
      concept that mu-opioid receptors located on myenteric neurons are coupled to
      Ca(2+)-dependent PKCs. After chronic sympathetic denervation, a reduced
      efficiency of this coupling may predominantly involve PKCbetaII, although also
      PKCbetaI and gamma, but not PKCalpha, may be implicated.

PMID- 19591808
TI  - Commentary: genome-based CNS drug discovery: D-amino acid oxidase (DAAO) as a
      novel target for antipsychotic medications: progress and challenges.
AB  - Antipsychotics, the drugs used currently for the treatment of schizophrenia,
      produce their therapeutic effects via the blockade of dopamine receptors. These
      compounds are, however, limited in their therapeutic efficacy and have side
      effect liabilities that also limit their use. Agents that produce antipsychotic
      effects by enhancing NMDA receptor function represent a viable alternative to
      dopamine antagonists. D-serine, is the prototype of this approach acting as a
      positive allosteric modulator of the NMDA receptor to enhance antipsychotic
      efficacy in the clinic. A newer approach to modulating NMDA receptor function,
      identified by gene association studies, is pLG72/DAOA (D-amino acid oxidase
      activator) a peptide that modulates D-amino acid oxidase (DAAO) activity,
      increasing endogenous levels of D-serine. While the initial association of DAOA
      with schizophrenia and its functional effects on DAAO activity have not been
      replicated, its identification has led to the development of several DAAO
      inhibitors, e.g., AS057278, CBIO and Compound 8, that are active in animal models
      of antipsychotic action. The complications in validating the G72 association with
      schizoprenia highlight the inherent challenges in translating gene-based, disease
      related associations to drug discovery targets.

PMID- 19591809
TI  - 2,3',4,4',5'-Pentamethoxy-trans-stilbene, a resveratrol derivative, is a potent
      inducer of apoptosis in colon cancer cells via targeting microtubules.
AB  - Resveratrol, a naturally occurring polyphenolic antioxidant, is a compound
      holding promise for cancer chemoprevention. Previous studies suggest that
      2,3',4,5'-tetramethoxy-trans-stilbene (TMS) and 3,4,4',5,-tetramethoxy-trans
      stilbene (MR-4), both of which are derivatives of resveratrol, are potent
      apoptosis-inducing agents with clinical potential. In this study, we chemically
      synthesized 2,3',4,4',5'-pentamethoxy-trans-stilbene (PMS), the hybrid molecule
      of TMS and MR-4, and determined its effects on colon cancer growth. When compared
      with its parent compounds, PMS displayed more potent in vitro anti-mitogenic
      effect on colon cancer cells (Caco-2, HT-29 and SW1116). Moreover, PMS inhibited
      tumor growth in vivo in a colon cancer xenograft model. In this connection, PMS
      strongly induced apoptosis in HT-29 cells as evidenced by increased PARP
      cleavage, DNA fragmentation, and accumulation of sub-G(1) population. Further
      mechanistic analysis revealed that PMS enhanced the polymerization of
      microtubules, which was followed by G(2)/M mitotic arrest and caspase-dependent
      apoptosis. The activation of caspases-3, -7, -8, and -9 was involved in PMS
      induced apoptosis with concomitant down-regulation of the pro-survival PI3K/Akt
      signaling. Collectively, these data suggest that PMS is a potent inducer of
      apoptosis via targeting microtubules and may merit investigation as a potential
      chemoprophylactic and therapeutic agent for colon cancer.

PMID- 19591810
TI  - Opiates inhibit paclitaxel uptake by P-glycoprotein in preparations of human
      placental inside-out vesicles.
AB  - The use of either methadone or buprenorphine for treatment of the pregnant opiate
      dependent patient improves maternal and neonatal outcome. However, patient
      outcomes are often complicated by neonatal abstinence syndrome (NAS). The
      incidence and severity of NAS should depend on opiate concentration in the fetal
      circulation. Efflux transporters expressed in human placental brush border
      membranes decrease fetal exposure to medications by their extrusion to the
      maternal circulation. Accordingly, the concentration of either methadone or
      buprenorphine in the fetal circulation is, in part, dependent on the activity of
      the efflux transporters. The objective of this study was to characterize the
      activity of P-gp and its interaction with opiates in the placental apical
      membrane. Therefore, brush border membrane vesicles were prepared from human
      placenta. The vesicles were oriented approximately 75% inside-out, exhibited
      saturable ATP-dependent uptake of P-gp substrate [(3)H]-paclitaxel with an
      apparent K(t) of 66+/-38 nM and V(max) of 20+/-3 pmol mg protein (-1)min(-1).
      Methadone, buprenorphine, and morphine inhibited paclitaxel transport with
      apparent K(i) of 18, 44, and 90 microM, respectively. Our data indicate that a
      method has been established to determine the activity of the efflux transporter P
      gp, expressed in placental brush border membranes, and the kinetics for the
      transfer of its prototypic substrate paclitaxel. Furthermore, the method was used
      to determine the effects of methadone, buprenorphine, and morphine on paclitaxel
      transfer by placental P-gp and revealed that they have higher affinity to the
      transporter than its classical inhibitor verapamil (K(i), 300 microM).

PMID- 19591811
TI  - Tanshinone IIA triggers p53 responses and apoptosis by RNA polymerase II upon DNA
      minor groove binding.
AB  - Our previous work has shown that tanshinone IIA (Tan IIA) is a DNA minor groove
      binder instead of an intercalator as previously thought. In this study, we have
      further demonstrated that the molecular antitumor pharmacology of Tan IIA is
      dependent on its groove-binding capability. First, we investigated the structure
      damage to duplex DNA upon Tan IIA binding using circular dichroism spectra.
      Subsequently, we performed western blot, flow cytometry analysis, chromatin
      immunoprecipitation, and quantitative real-time PCR to illustrate the RNAPII
      degradation, phosphorylation, and distribution along the transcribed gene in H22
      cells exposed to Tan IIA. In addition, p53 activation and apoptosis induction in
      both cultured H22 cells and in mice bearing the ascitic-type H22 were measured
      following Tan IIA treatment. It was revealed that Tan IIA decreases the level of
      RNAPII by altering DNA structure. At the low dose range (0.2-4 microM) of Tan IIA
      exposure, the DNA structure damage results in the inhibition of RNAPII binding to
      DNA and the initiation of RNAPII phosphorylation, while higher concentrations of
      Tan IIA (4-20 microM) cause complete phosphorylation and degradation of RNAPII
      followed by p53 activation and apoptosis. A similar apoptosis induction by RNAPII
      was observed in animals. Apoptosis of tumor cells from ascitic fluid was not
      detected until RNAPII levels were downregulated by Tan IIA, which requires 40
      mg/kg body weight of Tan IIA. It was concluded that DNA-conformational-damage
      dependent RNAPII response upon groove binding is the molecular basis of the
      antitumor property of Tan IIA, in vivo and in vitro.

PMID- 19591812
TI  - Functional consequences of genetic variation in primates on tyrosine hydroxylase
      (TH) expression in vitro.
AB  - Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis, is
      known to contain naturally occurring genetic variation in it's promoter region
      that associates with a number of neuropsychological disorders. As such, examining
      non-coding regions is important for understanding tyrosine hydroxylase function
      in human health and disease. We examined approximately 2 kb upstream of the
      translation start site within humans and non-human primates to obtain a fine
      resolution map of evolutionarily and functionally relevant cis-regulatory
      differences. Our study investigated Macaca mulatta, Pan troglodytes, Gorilla
      gorilla, and Homo sapiens haplotypes using transient dual-luciferase transfection
      in three neuroblastoma cell lines to assay the impact of naturally occurring
      sequence variation on expression level. In addition to trans effects between cell
      lines, there are several significant expression differences between primate
      species, but the most striking difference was seen between human haplotypes in
      one cell line. Underlying this variation are numerous sequence polymorphisms, two
      of which influence expression within humans in a non-additive and cell line
      specific manner. This study highlights functional consequences of tyrosine
      hydroxylase genetic variation in primates. Additionally, the results emphasize
      the importance of examining more than one cell line, the existence of multiple
      functional variants in a given promoter region and the presence of non-additive
      cis-interactions.

PMID- 19591814
TI  - Prospective and retrospective primary prevention of hemoglobinopathies in
      multiethnic societies.
AB  - OBJECTIVES: This review emphasizes the need for adapted prevention strategies in
      areas where severe hemoglobin disorders are endemic and in non-endemic countries
      where large immigrant groups are living. DESIGN AND METHODS: Screening versus
      carrier diagnostics upon medical versus ethnic indication, ethical issues
      associated with carrier screening, information to multiethnic carriers and
      practical aspects of laboratory diagnostics are discussed. RESULTS AND
      DISCUSSION: School screening is a valid option but needs follow up until partner
      choice. Premarital carrier diagnostics upon ethnic indication needs motivated
      GP's and might implicate (female) stigmatization in particular cultures. Early
      pregnancy is the best moment regarding the motivation, but needs rapid molecular
      analysis when a couple at risk seeks prevention. Neonatal screening is feasible
      when the organization is already present for other diseases and may offer
      retrospective as well as prospective primary prevention when all carriers are
      reported. Problems to be expected while implementing neonatal screening are
      summarized.

PMID- 19591813
TI  - Regulation of protein kinase C isozymes during early postnatal hippocampal
      development.
AB  - During neonatal hippocampal development, serotonin 1A receptor-mediated signaling
      initially employs PKCepsilon to boost neuronal proliferation and then uses
      PKCalpha to promote synaptogenesis. Such stage-specific involvement of a PKC
      isozyme could be determined by its relative expression level. In mouse
      hippocampi, we detected relatively low levels of alpha, beta, gamma, and delta
      isozymes at postnatal days 2-6 (P2-6), which was followed by a large increase in
      their expression. In contrast, the PKC isozymes epsilon and theta were relatively
      abundant at P6, following which they underwent a further increase by P15.
      Comparison with purified proteins confirmed that the PKCepsilon levels at P6 and
      P15 were respectively 1.75 and 7.36 ng per 60 microg of protein, whereas PKCalpha
      levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 microg of
      protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than
      PKCalpha. Consequently, signaling cascades could use the relatively abundant
      PKCepsilon (and possibly PKCtheta) molecules for early events at P2-6 (e.g.
      neurogenesis), following which PKCalpha (and the beta, gamma, or delta isozymes)
      could guide maturation or apoptosis. Notably, at P6 but not P15, PKCepsilon, was
      localized to the nuclei of neuroblasts, probably directing mitosis. In contrast,
      at P15 but not P6, PKCalpha was highly expressed in the processes of the
      differentiated hippocampal neurons. In summary, PKC isozymes follow differential
      profiles of expression in neonatal hippocampus and the relative abundance of each
      may determine its mode and stage of involvement in hippocampal development.

PMID- 19591815
TI  - Clinical laboratory reference intervals in pediatrics: the CALIPER initiative.
AB  - OBJECTIVE AND RATIONALE: Reference intervals provided on laboratory reports are
      essential for appropriate interpretation of test results, and can significantly
      impact clinical decision-making and the quality of patient care. Careful
      determination and/or validation of reference intervals by the laboratory for use
      in the patient population it serves are therefore important to ensure their
      proper utility. Unfortunately, critical gaps currently exist in accurate and up
      to-date pediatric reference intervals for accurate interpretation of laboratory
      tests performed in children and adolescents. These critical gaps in the available
      pediatric laboratory reference intervals have the clear potential of contributing
      to erroneous diagnosis or misdiagnosis of many diseases of childhood and
      adolescence. Most of the available "normal" ranges for laboratory tests were
      determined over 2 decades ago on older instruments and technologies, and are no
      longer relevant considering the current testing technology used by clinical
      laboratories. It is thus critical and of utmost urgency that a more acceptable
      and comprehensive database be established. DISCUSSION AND CONCLUSION: In the
      present review, we discuss the considerations and challenges faced when
      generating and validating reference intervals in accordance to the current
      guidelines published by the Clinical Laboratory Standards Institute (CLSI). We
      raise particular attention to the present-day deficiencies in available pediatric
      reference intervals, and highlight the special issues and unique difficulties
      that are additionally faced when establishing reference intervals in children.
      Finally, we highlight a recent Canadian initiative, the CALIPER project, whose
      mandate is to establish and maintain a database of comprehensive and up-to-date
      pediatric reference intervals to be eventually made available to all clinical
      laboratories worldwide.

PMID- 19591816
TI  - The significance of the hemoglobin A(2) value in screening for
      hemoglobinopathies.
AB  - BACKGROUND AND OBJECTIVE: The inherited hemoglobinopathies are a large group of
      disorders that include thalassemias and hemoglobin variants. Accurate
      determination of the carrier phenotype is essential for detecting couples at risk
      for producing offspring with hemoglobinopathy. Heterozygous beta-thalassemia is
      usually silent at the clinical level. His phenotype is characterized by
      microcytosis and hypochromia with increased hemoglobin A(2) (HbA(2)) value.
      Therefore, HbA(2) determination plays a key role in screening programs for
      hemoglobinopathy. The aim of this review is to address and suggest an approach
      for reducing or abolishing hemoglobinopathy screening mistakes. DESIGN AND
      METHODS: Quantitative methods for HbA(2) value determination, comment on the
      accuracy of the test and on the interpretation of data were discussed. The most
      probable diagnostic conclusion based on the HbA(2) level, hemoglobin pattern,
      hematological parameters and iron markers was suggested in this review. RESULTS:
      Hemoglobinopathies are the only genetic disease where it is possible to detect
      carriers using hematological findings rather than DNA analysis. However,
      hematological diagnosis is sometimes presumptive, and in these cases, DNA
      analysis becomes necessary. Complete screening is based on the detection of red
      cell indices, HbA(2), HbF and hemoglobin variant values. In particular, HbA(2)
      determination plays a key role in screening programs for beta-thalassemia because
      a small increase in this fraction is one of the most important markers of beta
      thalassemia heterozygous carriers. CONCLUSION: Genetic factors both related and
      unrelated to the beta- and alpha-globin gene clusters, iron metabolism,
      endocrinological disorders, and some types of anemia, together with intra- and
      inter-laboratory variations in HbA(2) determination, may cause difficulties in
      evaluating this measurement in screening programs for hemoglobinopathies.
      Therefore, knowledge of all these issues is important for reducing or eliminating
      the risk of mistakes in screening programs for hemoglobinopathies.

PMID- 19591817
TI  - Retained structural integrity of collagen and elastin within cryopreserved human
      heart valve tissue as detected by two-photon laser scanning confocal microscopy.
AB  - Cryopreservation is commonly used for the long-term storage of heart valve
      allografts. Despite the excellent hemodynamic performance and durability of
      cryopreserved allografts, reports have questioned whether cryopreservation
      affects the valvular structural proteins, collagen and elastin. This study uses
      two-photon laser scanning confocal microscopy (LSCM) to evaluate the effect of
      cryopreservation on collagen and elastin integrity within the leaflet and conduit
      of aortic and pulmonary human heart valves. To permit pairwise comparisons of
      fresh and cryopreserved tissue, test valves were bisected longitudinally with one
      segment imaged fresh and the other imaged after cryopreservation and brief
      storage in liquid nitrogen. Collagen was detected by second harmonic generation
      (SHG) stimulation and elastin by autofluorescence excitation. Qualitative
      analysis of all resultant images indicated the maintenance of collagen and
      elastin structure within leaflet and conduit post-cryopreservation. Analysis of
      the optimized percent laser transmission (OPLT) required for full dynamic range
      imaging of collagen and elastin showed that OPLT observations were highly
      variable among both fresh and cryopreserved samples. Changes in donor-specific
      average OPLT in response to cryopreservation exhibited no consistent directional
      trend. The donor-aggregated results predominantly showed no statistically
      significant change in collagen and elastin average OPLT due to cryopreservation.
      Since OPLT has an inverse relationship with structural signal intensity, these
      results indicate that there was largely no statistical difference in collagen and
      elastin signal strength between fresh and cryopreserved tissue. Overall, this
      study indicates that the conventional cryopreservation of human heart valve
      allografts does not detrimentally affect their collagen and elastin structural
      integrity.

PMID- 19591818
TI  - Regulation of sperm gene expression by the GATA factor ELT-1.
AB  - Cell fate specification is mediated primarily through the expression of cell-type
      specific genes. The regulatory pathway that governs the sperm/egg decision in the
      hermaphrodite germ line of Caenorhabditis elegans has been well characterized,
      but the transcription factors that drive these developmental programs remain
      unknown. We report the identification of ELT-1, a GATA transcription factor that
      specifies hypodermal fate in the embryo, as a regulator of sperm-specific
      transcription in the germ line. Computational analysis identified a conserved
      bipartite sequence element that is found almost exclusively in the promoters of a
      number of sperm genes. ELT-1 was recovered in a yeast one-hybrid screen for
      factors that bind to that sperm consensus site. In vitro assays defined the sperm
      consensus sequence as an optimal binding site for ELT-1. We determined that
      expression of elt-1 is elevated in the sperm-producing germ line, and that ELT-1
      is required for sperm function. Deletion of the ELT-1 binding site from a sperm
      promoter abrogates sperm-specific expression of a reporter transgene. This work
      demonstrates a role for the ELT-1 transcription factor in sperm, and provides a
      critical link between the germ line sex determination program and gamete-specific
      gene expression.

PMID- 19591820
TI  - Drosophila Cyclin J is a mitotically stable Cdk1 partner without essential
      functions.
AB  - Cyclin J is a cyclin family member that appears to have evolved before the
      metazoan radiation. Its evolutionary conservation argues for an important role
      but functional characterizations of Cyclin J have remained very limited. In
      Drosophila, Cyclin J is expressed only in females. Using transgenic Drosophila
      lines expressing Cyclin J versions with N- or C-terminal GFP extensions, we
      demonstrate that it is expressed exclusively in the germline. After low level
      expression in all nuclei within the germarium, it gets highly enriched in the
      germinal vesicle within the oocyte until stage 12 of oogenesis, followed by
      disappearance after germinal vesicle breakdown before the first meiotic division.
      Surprisingly, Cyclin J is not required for female fertility. Chromosome
      segregation during female meiosis, as well as the rapid early embryonic cell
      cycles after fertilization, occurs normally in the complete absence of Cyclin J.
      Cyclin J with EGFP fused at either N- or C-terminus binds to Cdk1 and not to
      Cdk2. However, in contrast to the other known Cdk1 partners, the A- and B-type
      cyclins, Cyclin J is not degraded during mitosis.

PMID- 19591819
TI  - The LIM homeodomain transcription factors Lhx6 and Lhx7 are key regulators of
      mammalian dentition.
AB  - Genes encoding LIM homeodomain transcription factors are implicated in cell type
      specification and differentiation during embryogenesis. Two closely related
      members of this family, Lhx6 and Lhx7, are expressed in the ectomesenchyme of the
      maxillary and mandibular processes and have been suggested to control patterning
      of the first branchial arch (BA1) and odontogenesis. However, mice homozygous for
      single mutations either have no cranial defects (Lhx6) or show only cleft palate
      (Lhx7). To reveal the potential redundant activities of Lhx6 and Lhx7 in cranial
      morphogenesis, we generated mice with all combinations of wild-type and mutant
      alleles. Double homozygous mice have characteristic defects of the cranial
      skeleton and die shortly after birth, most likely because of cleft palate. In
      addition, Lhx6/7 deficient embryos lack molar teeth. The absence of molars in
      double mutants is not due to patterning defects of BA1 but results from failure
      of specification of the molar mesenchyme. Despite molar agenesis, Lhx6/7
      deficient animals have normal incisors which, in the maxilla, are flanked by a
      supernumerary pair of incisor-like teeth. Our experiments demonstrate that the
      redundant activities of the LIM homeodomain proteins Lhx6 and Lhx7 are critical
      for craniofacial development and patterning of mammalian dentition.

PMID- 19591822
TI  - Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population-
      implications for association study design and clinical genetic testing services.
AB  - We investigated the prevalence of genotypes/alleles of single nucleotide
      polymorphisms (SNP) and haplotypes defined by them in three genes in which
      variations are associated with venous thromboembolism in 80 Sinhalese, 80 Sri
      Lankan Tamils and 80 Moors in the Sri Lankan population and compared the SNP data
      with that of other populations in Southern India and haplotype data with that of
      HapMap populations. The genes and polymorphisms investigated were
      Methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133), 1298A>C
      (rs1801131), 1317T>C, 1793G>A (rs2274976); Factor V (F5) - 1691G>A (rs6025) and
      4070A>G (rs1800595); and prothrombin (F2) - 20210G>A (rs1799963). The
      polymorphisms were genotyped using PCR/RFLP methods. The prevalence of the
      variant alleles of each polymorphism in the Sinhalese, Tamils, and Moors was
      MTHFR 677T: Sinhalese - 13%, Tamils - 9%, Moors - 9%. 1317T>C: Sinhalese - 0%;
      Tamils - 0%; Moors - 0%. 1793A: Sinhalese - 19%, Tamils - 19%, Moors - 19%. F5
      1691A: Sinhalese - 2%, Tamils - 3%, Moors - 2%. 4070G: Sinhalese - 6%, Tamils -
      5%, Moors - 8%. F2 20210A: Sinhalese - 0%, Tamils - 0%, Moors - 0%. The
      frequencies observed were similar to data from other South Indian populations;
      the haplotype data showed haplotypes unique to the Sri Lankan population when
      compared to HapMap populations. rs9651118 was identified as a SNP that splits the
      haplotypes harbouring the functionally significant 677T allele in the MTHFR gene.
      This data would be useful in planning genetic association studies in the Sri
      Lankan population and in deciding on which genetic variants should be tested in a
      clinical genetic testing service.

PMID- 19591823
TI  - The inflammatory component of Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is intimately linked to several aspects of the host immune
      system. KS development is linked to immunodeficiency in several clinical
      epidemiological settings. The development of KS at local inflammatory sites has
      also been documented. Inflammatory cells are almost always present within KS
      lesions. Depending upon the inflammatory milieu, KS lesions may progress or
      regress. Not surprisingly, iatrogenic manipulation of host immunity with drugs
      may provoke KS growth and/or flare. Given the close association between KS and
      the immune system, the etiologic agent Kaposi Sarcoma Herpesvirus has developed a
      variety of mechanisms to evade the host immune system, all of which have cleverly
      evolved to promote oncogenesis and viral persistence.

PMID- 19591824
TI  - DLEU2, frequently deleted in malignancy, functions as a critical host gene of the
      cell cycle inhibitory microRNAs miR-15a and miR-16-1.
AB  - The microRNAs miR-15a and miR-16-1 are downregulated in multiple tumor types and
      are frequently deleted in chronic lymphocytic leukemia (CLL), myeloma and mantle
      cell lymphoma. Despite their abundance in most cells the transcriptional
      regulation of miR-15a/16-1 remains unclear. Here we demonstrate that the putative
      tumor suppressor DLEU2 acts as a host gene of these microRNAs. Mature miR-15a/miR
      16-1 are produced in a Drosha-dependent process from DLEU2 and binding of the Myc
      oncoprotein to two alterative DLEU2 promoters represses both the host gene
      transcript and levels of mature miR-15a/miR-16-1. In line with a functional role
      for DLEU2 in the expression of the microRNAs, the miR-15a/miR-16-1 locus is
      retained in four CLL cases that delete both promoters of this gene and expression
      analysis indicates that this leads to functional loss of mature miR-15a/16-1. We
      additionally show that DLEU2 negatively regulates the G1 Cyclins E1 and D1
      through miR-15a/miR-16-1 and provide evidence that these oncoproteins are subject
      to miR-15a/miR-16-1-mediated repression under normal conditions. We also
      demonstrate that DLEU2 overexpression blocks cellular proliferation and inhibits
      the colony-forming ability of tumor cell lines in a miR-15a/miR-16-1-dependent
      way. Together the data illuminate how inactivation of DLEU2 promotes cell
      proliferation and tumor progression through functional loss of miR-15a/miR-16-1.

PMID- 19591821
TI  - High-resolution gene expression analysis of the developing mouse kidney defines
      novel cellular compartments within the nephron progenitor population.
AB  - The functional unit of the kidney is the nephron. During its organogenesis, the
      mammalian metanephric kidney generates thousands of nephrons over a protracted
      period of fetal life. All nephrons are derived from a population of self-renewing
      multi-potent progenitor cells, termed the cap mesenchyme. However, our
      understanding of the molecular and cellular mechanisms underlying nephron
      development is at an early stage. In order to identify factors involved in
      nephrogenesis, we performed a high-resolution, spatial profiling of a number of
      transcriptional regulators expressed within the cap mesenchyme and early
      developing nephron. Our results demonstrate novel, stereotypic, spatially defined
      cellular sub-domains within the cap mesenchyme, which may, in part, reflect
      induction of nephron precursors. These results suggest a hitherto unappreciated
      complexity of cell states that accompany the assembly of the metanephric kidney,
      likely reflecting diverse regulatory actions such as the maintenance and
      induction of nephron progenitors.

PMID- 19591825
TI  - PKC-delta binds to E-cadherin and mediates EGF-induced cell scattering.
AB  - EGF is known to affect adherens junctions and disrupt cell-cell adhesion in a
      variety of carcinomas but the underlying mechanisms are not completely
      understood. Using human tumor epithelial cells overexpressing EGFR we
      demonstrated that EGF-induced cell scattering was mediated by protein kinase C
      delta (PKC-delta). PKC-delta knockdown by siRNA significantly inhibited EGF
      induced internalization of E-cadherin into the cytoplasm and blocked cell
      scattering. EGF phosphorylated PKC-delta at Y311 and ectopic expression of the
      mutant Y311F prevented PKC-delta binding to E-cadherin and EGF-induced cell
      scattering. Moreover, depletion of Src using siRNA decreased EGF-induced
      phosphorylation of PKC-delta at Y311 and blocked scattering. Finally, EGF reduced
      expression of the tight junction protein, occludin, and this effect was also
      mediated by PKC-delta through Src. In summary, PKC-delta mediated the effects of
      EGF on adherens and tight junctions thereby playing an important role in cell
      cell adhesion with possible wider implications in tumor metastasis or epithelial
      to-mesenchymal transition.

PMID- 19591826
TI  - Neuroprotection of photoreceptors by direct delivery of erythropoietin to the
      retina of the retinal degeneration slow mouse.
AB  - The primary objectives of this study were to determine if erythropoietin (EPO) is
      neuroprotective to the photoreceptors in the retinal degeneration slow (rds)
      mouse in the absence of an increase in hematocrit and to determine if
      deglycosylated EPO (DEPO) is less neuroprotective. We performed subretinal
      injections of 10U EPO, DEPO or hyperglycosylated EPO (HEPO) in postnatal day 7
      rds mice. Whole eye EPO levels were quantified by ELISA at specified time points
      post-injection. TUNEL analysis, hematocrit, and immunohistochemistry were
      performed at postnatal day 20. Half of the amount of EPO measured immediately
      after injection was detected less than 1 h later. Twenty four hours later, EPO
      levels were 1000 times lower than the amount originally detected. Uninjected rds
      mice contained 36 +/- 2 TUNEL-positive cells/mm retina and PBS injected mice
      contained 17 +/- 3 TUNEL-positive cells/mm retina. EPO, DEPO, and HEPO treated
      rds retinas contained 5 +/- 2, 9 +/- 2, and 3 +/- 1 TUNEL-positive cells/mm
      retina, respectively. The hematocrit was 43% in control and 41% in treated rds
      mice Previous studies have shown neuroprotection of the retina by treatment with
      as little as 24-39 mU EPO/mg total protein in the eye. In this study, we detected
      40 mU/mg EPO in the eye 11 h after injection of 10 U EPO. Treatment with all
      forms of EPO tested was neuroprotective to the photoreceptors without a
      concomitant increase in hematocrit.

PMID- 19591827
TI  - Gut microbiota affects lens and retinal lipid composition.
AB  - The gut microbiota affects host lipid metabolism and is considered an
      environmental factor that contributes to development of obesity. To investigate
      whether the gut microbiota affects the eye lipidome, we performed comprehensive
      lipidomic profiling of lens and retina from conventionally raised and germ-free
      mice. Conventionally raised mice had diminished phosphatidylcholines in the lens
      and elevated ethanolamine plasmalogens in the retina. Diminishment of lens
      phosphatidylcholines in the presence of gut microbiota suggests that the
      conventionally raised mice are exposed over time to more oxidative stress than
      germ-free mice. Consistent with this, their lifespan is also shorter. Our
      findings may open a new area of investigation how modulation of gut microbiota
      affects the eye health.

PMID- 19591828
TI  - Morphological and hydrodynamic correlates in monkey eyes with laser induced
      glaucoma.
AB  - This study investigated the relationship between decreased outflow facility (C)
      and changes in hydrodynamic aqueous humor outflow patterns and morphology in
      cynomolgus monkey eyes with unilateral chronically elevated intraocular pressure
      (IOP). Argon laser photocoagulation burns to the trabecular meshwork (TM) were
      made in one eye of each monkey (N = 3), leaving the contralateral eye as a
      normotensive control. IOPs were followed by pneumatonometry for 16-70 months. C
      was measured by fluorophotometry before sacrifice. To label the hydrodynamic
      patterns of outflow, the eyes were enucleated and perfused with fluorescent
      microspheres (0.5 microm; 0.002%) at the last pressure measured before death
      minus 7 mmHg. The eyes were perfusion-fixed at the same pressure. Confocal images
      were taken along the inner wall (IW) of the Schlemm's canal (SC). The total
      length (TL) and the filtration length (FL) of the IW decorated by tracers were
      measured in frontal sections. The average percent effective filtration length
      (PEFL = FL/TL) was calculated for each eye. Sections exhibiting SC were processed
      and examined under light and electron microscopy. The average IOP was
      significantly higher in laser-treated eyes (mean +/- SD = 61.33 +/- 4.16 mmHg)
      than controls (22.67 +/- 4.16 mmHg, P = 0.002). The average C was 13-fold lower
      in laser-treated eyes (0.03 +/- 0.02 microl/min/mmHg) than controls (0.39 +/-
      0.17 microl/min/mmHg, P = 0.057). By confocal microscopy, in control eyes, SC was
      open and a segmental distribution of microspheres was found in the TM with a
      greater concentration near the collector channel (CC) ostia. Much less tracer
      labeling was seen along SC in laser-treated eyes than control eyes. The average
      PEFL in controls (47.47 +/- 10.79%) was 6-fold larger than in laser-treated eyes
      (8.40 +/- 4.81%, P = 0.048). The average distance between the inner and outer
      wall of SC was 5-fold greater in control eyes (18.99 +/- 6.03 microm) than in
      laser-treated eyes (3.47 +/- 0.33 microm, P = 0.048). By light microscopy, there
      was extensive pigmentation throughout the TM, denser extracellular matrix in the
      JCT region, and most of SC collapsed with focal herniations of the IW and JCT
      protruding into the CC ostia in laser-treated eyes. By electron microscopy, few
      or no microspheres were observed in laser-treated areas and the areas with SC
      collapse. More microspheres were observed near the CC ostia area in non-lasered
      areas. In conclusion, in the laser-induced glaucoma model, laser damage results
      in a reduction in the available area for outflow across the IW of SC which
      contributes to the decrease in C and thus elevation of the IOP. Constriction of
      SC, caused by the chronic elevation of IOP, further decreases the available area
      for outflow across the IW which decreases C even more in a vicious cycle. This
      study suggests that the available area for aqueous humor outflow across the IW of
      SC may play a role in regulating outflow resistance and maintaining IOP.

PMID- 19591829
TI  - Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES
      cells.
AB  - Increased modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc)
      has been implicated in the development of diabetic cardiomyopathy. We used the
      well-characterized ES cells (Nkx2.5GFP knock-in ES cells), to investigate the
      role of O-GlcNAcylation in cardiomyocyte development. O-GlcNAcylation decreased
      in differentiating ES cells, as did the expression of O-GlcNAc transferase.
      Increasing O-GlcNAcylation with glucosamine or by inhibiting N
      acetylglucosaminidase (streptozotocin or PUGNAc) decreased the number of
      cardiomyocyte precursors and cardiac-specific gene expression. On the other hand,
      decreasing O-GlcNAcylation with an inhibitor of glutamine fructose-6-phosphate
      amidotransferase (6-diazo-5-oxo-norleucine) increased cardiomyocyte precursors.
      These results suggest that excessive O-GlcNAcylation impairs cardiac cell
      differentiation in ES cells.

PMID- 19591831
TI  - Temporal analysis of early immune responses in patients with acute hepatitis B
      virus infection.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) causes more than 1 million deaths
      annually from immune-mediated liver damage. The long incubation period has been
      difficult to study; by the time most patients present, massive viremia and the
      majority of viral clearance have already occurred. The aim of this study was to
      investigate the contribution of innate and adaptive immune mechanisms in early
      acute HBV through access to an unusual cohort of patients sampled in the
      preclinical phase and followed up to resolution of their infection. METHODS:
      Twenty-one patients with acute HBV were studied, 8 of them from before the peak
      of viremia. Circulating innate cytokines were quantitated by enzyme-linked
      immunosorbent assay and natural killer (NK) and T-cell effector function by flow
      cytometry. Results were correlated with temporal changes in viral load, serology,
      and liver inflammation and compared with healthy controls. RESULTS: Type I
      interferon (IFN) remained barely detectable throughout, with concentrations no
      higher than those found in healthy controls. Similarly, interleukin-15 and IFN
      lambda1 were not induced during peak viremia. NK cell activation and capacity for
      IFN-gamma production were reduced at peak viremia. Early functional HBV-specific
      CD4 and CD8 T-cell responses were attenuated as viral load increased and
      recovered again as infection resolved. The transient inhibition of NK and T-cell
      responses coincided with a surge in the immunosuppressive cytokine interleukin-10
      accompanying HBV viremia. CONCLUSIONS: The early stages of acute HBV are
      characterized by induction of interleukin-10 rather than type I IFN, accompanied
      by a temporary attenuation of NK and T-cell responses.

PMID- 19591830
TI  - Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model
      of hemochromatosis.
AB  - BACKGROUND AND AIMS: Mutations in HFE are the most common cause of the iron
      overload disorder hereditary hemochromatosis. Levels of the main iron regulatory
      hormone, hepcidin, are inappropriately low in hereditary hemochromatosis mouse
      models and patients with HFE mutations, indicating that HFE regulates hepcidin.
      The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is an important
      endogenous regulator of hepcidin expression. We investigated whether HFE is
      involved in BMP6-SMAD regulation of hepcidin expression. METHODS: The BMP6-SMAD
      pathway was examined in Hfe knockout (KO) mice and in wild-type (WT) mice as
      controls. Mice were placed on diets of varying iron content. Hepcidin induction
      by BMP6 was examined in primary hepatocytes from Hfe KO mice; data were compared
      with those of WT mice. RESULTS: Liver levels of Bmp6 messenger RNA (mRNA) were
      higher in Hfe KO mice; these were appropriate for the increased hepatic levels of
      iron in these mice, compared with WT mice. However, levels of hepatic
      phosphorylated Smad 1/5/8 protein (an intracellular mediator of Bmp6 signaling)
      and Id1 mRNA (a target gene of Bmp6) were inappropriately low for the body iron
      burden and Bmp6 mRNA levels in Hfe KO, compared with WT mice. BMP6 induction of
      hepcidin expression was reduced in Hfe KO hepatocytes compared with WT
      hepatocytes. CONCLUSIONS: HFE is not involved in regulation of BMP6 by iron, but
      does regulate the downstream signals of BMP6 that are triggered by iron.

PMID- 19591832
TI  - Juvenile hormone and the ontogeny of cockroach aggression.
AB  - Our previous study [Kou et al., 2008. Juvenile hormone levels are increased in
      winners of cockroach fights. Horm. Behav. 52, 252-260] showed that the basic
      principle of the challenge hypothesis (hormone levels can respond to social
      stimuli to modulate aggression in vertebrates] could be applied to juvenile
      hormone (JH) levels and aggression in the lobster cockroach Nauphoeta cinerea. In
      that study, 80- to 85-day-old socially naive males were used, as fighting is much
      more easily initiated in these older animals than in younger males, and JH III
      levels in the dominant were found to be significantly increased after an
      encounter compared to before the encounter and were significantly higher than
      those in the subordinates. In N. cinerea, newly emerged males usually show no
      aggressiveness towards each other and aggression is only initiated after several
      days of close contact. To investigate the development of aggression from an early
      age, in the present study, newly emerged males were paired to investigate the
      relationship between JH levels and aggression. The results showed that injection
      of JH III significantly increased the probability of the young males being fight
      winners. In each age group in which aggression was initiated, the dominants had
      significantly higher JH levels than either the subordinates or the same aged non
      fighters. JH injection of subordinates on the day of rank establishment had no
      effect on the probability of rank switch. These results indicate that, (i) in
      newly emerged male pairs, JH plays a decisive role in rank establishment and the
      fact that dominant status is significantly associated with a higher JH titer and
      subordinate status with a lower JH titer is consistent with the basic principle
      of the challenge hypothesis, and (ii) after rank establishment, the lack of
      effect of JH treatment on rank change is consistent with the idea of "social
      inertia" in vertebrates.

PMID- 19591833
TI  - Effects of aggressive encounters on plasma corticosteroid-binding globulin and
      its ligands in white-crowned sparrows.
AB  - In birds, corticosteroid-binding globulin (CBG) binds corticosterone,
      progesterone and testosterone. The concentration of each ligand can alter the
      binding of the other ligands through competitive interactions. Thus, an increase
      in corticosterone or progesterone may displace testosterone bound to CBG, leading
      to an increase in bioactive free testosterone levels without affecting total
      testosterone levels in the circulation. Aggressive interactions increase plasma
      total testosterone levels in some birds but not in others. Here, we tested the
      hypothesis that aggressive encounters in the late breeding season would not
      increase total testosterone levels in plasma, but would alter CBG, total
      corticosterone or total progesterone levels in such a way as to modify the number
      of available binding sites and therefore occupancy by testosterone. A marked
      decrease in CBG occupancy by testosterone would indirectly suggest an increase in
      free testosterone levels in plasma. Wild male white-crowned sparrows were exposed
      to a simulated territorial intrusion (STI) or control for 30 min. Subjects were
      then caught and bled. We measured CBG using a ligand-binding assay and
      corticosterone, progesterone and testosterone using highly sensitive
      radioimmunoassays. STI significantly increased aggressive behaviors but did not
      affect plasma total testosterone levels. STI significantly increased plasma CBG
      and total corticosterone levels and decreased plasma total progesterone levels.
      We predict that CBG occupancy by corticosterone will increase slightly following
      an aggressive encounter. However, this small change is unlikely to increase free
      testosterone levels, because of the large number of seemingly unoccupied CBG
      binding sites in these subjects.

PMID- 19591835
TI  - The cardiac pacemaker current.
AB  - In mammals cardiac rate is determined by the duration of the diastolic
      depolarization of sinoatrial node (SAN) cells which is mainly determined by the
      pacemaker I(f) current. f-channels are encoded by four members of the
      hyperpolarization-activated cyclic nucleotide-gated gene (HCN1-4) family. HCN4 is
      the most abundant isoform in the SAN, and its relevance to pacemaking has been
      further supported by the discovery of four loss-of-function mutations in patients
      with mild or severe forms of cardiac rate disturbances. Due to its selective
      contribution to pacemaking, the I(f) current is also the pharmacological target
      of a selective heart rate-reducing agent (ivabradine) currently used in the
      clinical practice. Albeit to a minor extent, the I(f) current is also present in
      other spontaneously active myocytes of the cardiac conduction system
      (atrioventricular node and Purkinje fibres). In working atrial and ventricular
      myocytes f-channels are expressed at a very low level and do not play any
      physiological role; however in certain pathological conditions over-expression of
      HCN proteins may represent an arrhythmogenic mechanism. In this review some of
      the most recent findings on f/HCN channels contribution to pacemaking are
      described.

PMID- 19591836
TI  - Constitutive CaMKII activity regulates Na+ channel in rat ventricular myocytes.
AB  - The cardiac voltage-gated Na(+) channel controls the upstroke of action potential
      and membrane excitability. The Na(+) channel associates with Ca(2+)/CaM-dependent
      protein kinase (CaMKII), but the role of CaMKII on Na(+) channel activity in the
      resting state is not clear. In this report, we investigated whether CaMKII
      constitutively regulates Na(+) currents (I(Na)), independent of Ca(2+) influx in
      rat ventricular myocytes using patch clamp technique. CaMKII inhibition (by KN93
      or autocamtide-related inhibitory peptide) caused a negative shift in I(Na)
      steady-state inactivation and delayed recovery from slow inactivation, limiting
      channel availability. The reduction of I(Na) was 29.47+/-3.01% at a holding
      potential (V(h)) of -120 mV and it increased to 77.70+/-7.92% when V(h) was -70
      mV, suggesting that near the resting membrane potential, three-quarters of I(Na)
      depends on CaMKII action. CaMKII inhibition also enhanced intermediate
      inactivation, as well as delayed recovery from fast inactivation, and decreased
      late I(Na). KN92, an inactive analog of KN93, had no effect on I(Na). Using an
      antibody against phosphorylated (activated) CaMKII, we found that constitutively
      active CaMKII co-immunoprecipitated with Na(+) channels under resting conditions.
      CaMKII inhibitors reduced the level of phosphorylated CaMKII, which correlated
      with the degree of reduction in channel availability. These data suggest that
      CaMKII in an active form contributes to regulating I(Na). Finally, we observed a
      drastic reduction in the upstroke velocity of action potentials upon CaMKII
      inhibition. In conclusion, CaMKII constitutively regulates cardiac Na(+) channel
      and this regulatory mechanism is important for the maintenance of Na(+) channel
      characteristics under physiological conditions.

PMID- 19591834
TI  - Characterisation of a fatty acid and retinol binding protein orthologue from the
      hookworm Ancylostoma ceylanicum.
AB  - Hookworms, bloodfeeding intestinal nematodes, infect nearly one billion people in
      resource limited countries and are a leading cause of anaemia and malnutrition.
      Like other nematodes, hookworms lack the capacity to synthesise essential fatty
      acids de novo and therefore must acquire those from exogenous sources. The cDNA
      corresponding to a putative Ancylostoma ceylanicum fatty acid and retinol binding
      protein-1 (AceFAR-1) was amplified from adult hookworm mRNA. Studies using
      quantitative reverse transcriptase real-time PCR demonstrate that AceFAR-1
      transcripts are most abundant in the earliest developmental stages of the
      parasite, and greater in females than males. Using in vitro assays, the
      recombinant AceFAR-1 (rAceFAR-1) was shown to bind individual fatty acids with
      equilibrium dissociation constants in the low micromolar range. The pattern of
      fatty acid uptake by live adult worms cultured ex vivo was similar to the in
      vitro binding profile of rAceFAR-1, raising the possibility that the native
      protein may be involved in acquisition of fatty acids by A. ceylanicum. Animals
      vaccinated orally with rAceFAR-1 and the mucosal adjuvant cholera toxin exhibited
      a statistically significant (40-47%) reduction in intestinal worm burden compared
      with controls immunized with antigen or adjuvant alone. Together, these data
      suggest a potential role for AceFAR-1 in hookworm biology, making it a
      potentially valuable target for drug and vaccine development.

PMID- 19591837
TI  - Distinct structural features of cyclothiazide are responsible for effects on peak
      current amplitude and desensitization kinetics at iGluR2.
AB  - Ionotropic glutamate receptors (iGluRs) mediate fast excitatory
      neurotransmission. Upon glutamate application, 2-amino-3-(3-hydroxy-5-methyl-4
      isoxazolyl)propionic acid receptors undergo rapid and almost complete
      desensitization that can be attenuated by positive allosteric modulators. The
      molecular mechanism of positive allosteric modulation has been elucidated
      previously by crystal structures of the ligand-binding core of iGluR2 in complex
      with, for example, cyclothiazide (CTZ). Here, we investigate the structure and
      function of CTZ and three closely related analogues NS1493, NS5206, and NS5217 at
      iGluR2, by X-ray crystallography and fast application patch-clamp
      electrophysiology. CTZ was the most efficacious and potent modulator of the four
      compounds on iGluR2(Q)(i) [E(max) normalized to response of glutamate: 754%
      (CTZ), 490% (NS1493), 399% (NS5206), and 476% (NS5217) and EC(50) in micromolar:
      10 (CTZ), 26 (NS1493), 43 (NS5206), and 48 (NS5217)]. The four modulators divide
      into three groups according to efficacy and desensitization kinetics: (1) CTZ
      increases the peak current efficacy twice as much as the three analogues and
      nearly completely blocks receptor desensitization; (2) NS5206 and NS5217 have low
      efficacy and only attenuate desensitization partially; (3) NS1493 has low
      efficacy but nearly completely blocks receptor desensitization. A hydrophobic
      substituent at the 3-position of the 1,1-dioxo-3,4-dihydro-2H
      benzo[e][1,2,4]thiadiazine ring system is important for compound efficacy, with
      the following ranking: norbornenyl (bicyclo[2.2.1]hept-2-ene)>cyclopentyl>methyl.
      The replacement of the norbornenyl moiety with a significantly less hydrophobic
      cyclopentane ring increases the flexibility of the modulator as the cyclopentane
      ring adopts various conformations at the iGluR2 allosteric binding site. The main
      structural feature responsible for a nearly complete block of desensitization is
      the presence of an NH hydrogen bond donor in the 4-position of the 1,1-dioxo-3,4
      dihydro-2H-benzo[e][1,2,4]thiadiazine ring system, forming an anchoring hydrogen
      bond to Ser754. Therefore, the atom at the 4-position of CTZ seems to be a major
      determinant of receptor desensitization kinetics.

PMID- 19591838
TI  - A computationally guided protein-interaction screen uncovers coiled-coil
      interactions involved in vesicular trafficking.
AB  - Mapping protein-protein interactions at a domain or motif level can provide
      structural annotation of the interactome. The alpha-helical coiled coil is among
      the most common protein-interaction motifs, and proteins predicted to contain
      coiled coils participate in diverse biological processes. Here, we introduce a
      combined computational/experimental screening strategy that we used to uncover
      coiled-coil interactions among proteins involved in vesicular trafficking in
      Saccharomyces cerevisiae. A number of coiled-coil complexes have already been
      identified and reported to play important roles in this important biological
      process. We identify additional examples of coiled coils that can form physical
      associations. The computational strategy used to prioritize coiled-coil
      candidates for testing dramatically improved the efficiency of discovery in a
      large experimental screen. As assessed by comprehensive yeast two-hybrid assays,
      computational prefiltering retained 90% of positive interacting pairs and
      eliminated >60% of negatives from a set of interaction candidates. The coiled
      coil-mediated interaction network elucidated using the combined
      computational/experimental approach comprises 80 coiled-coil associations between
      58 protein pairs, among which 21 protein interactions have not been previously
      reported in interaction databases and 26 interactions were previously known at
      the protein level but have now been localized to the coiled-coil motif. The
      coiled-coil-mediated interactions were specific rather than promiscuous, and many
      interactions could be recapitulated in a green fluorescent protein
      complementation assay. Our method provides an efficient route to discovering new
      coiled-coil interactions and uncovers a number of associations that may have
      functional significance for vesicular trafficking.

PMID- 19591841
TI  - G-domain dimerization orchestrates the tRNA wobble modification reaction in the
      MnmE/GidA complex.
AB  - MnmE and GidA are involved in the modification of wobble uridine to
      carboxymethylaminomethyl uridine in certain tRNAs. Malfunctioning of the human
      orthologs has been implicated in mitochondrial diseases. MnmE is a conserved G
      protein activated by dimerization. Here, we show that complex formation between
      MnmE and GidA involves large conformational changes that induce G-domain
      dimerization of MmnE and that GidA co-stimulates GTP hydrolysis on MnmE. Starting
      from a structural model of the complex, we identify interface mutations
      disrupting complex formation or communication. Although GidA does not directly
      contact the G-domains, conformational changes in MnmE, induced by G-domain
      dimerization in the triphosphate state, regulate the affinity for GidA. We
      developed a tRNA modification assay and demonstrate for the first time in vitro
      that the MnmE/GidA complex catalyzes incorporation of glycine into tRNA. An
      intact MnmE/GidA complex rather than their sequential action is crucial for in
      vitro modification. Since only GTP, but not GDP or non-hydrolyzable GTP analogs,
      drives the MnmE/GidA-catalyzed modification reaction, we conclude that GTP
      hydrolysis is essential for activity. We finally show that an active GTPase, an
      intact MnmE/GidA communication, and dimerization of G-domains are necessary for
      in vivo functioning since mutations disrupting either result in a respiratory
      deficient phenotype in yeast.

PMID- 19591840
TI  - Minimum-energy path for a u6 RNA conformational change involving protonation,
      base-pair rearrangement and base flipping.
AB  - The U6 RNA internal stem-loop (U6 ISL) is a highly conserved domain of the
      spliceosome that is important for pre-mRNA splicing. The U6 ISL contains an
      internal loop that is in equilibrium between two conformations controlled by the
      protonation state of an adenine (pK(a)=6.5). Lower pH favors formation of a
      protonated C-A(+) wobble pair and base flipping of the adjacent uracil. Higher pH
      favors stacking of the uracil and allows an essential metal ion to bind at this
      position. Here, we define the minimal-energy path for this conformational
      transition. To do this, we solved the U6 ISL structure at higher pH (8.0) in
      order to eliminate interference from the low-pH conformer. This structure reveals
      disruption of the protonated C-A(+) pair and formation of a new C-U pair, which
      explains the preference for a stacked uracil at higher pH. Next, we used nudged
      elastic band molecular dynamics simulations to calculate the minimum-energy path
      between the two conformations. Our results indicate that the C-U pair is dynamic,
      which allows formation of the more stable C-A(+) pair upon adenine protonation.
      After formation of the C-A(+) pair, the unpaired uracil follows a minor-groove
      base-flipping pathway. Molecular dynamics simulations suggest that the
      extrahelical uracil is stabilized by contacts with the adjacent helix.

PMID- 19591839
TI  - Ezrin induces long-range interdomain allostery in the scaffolding protein NHERF1.
AB  - Scaffolding proteins are molecular switches that control diverse signaling
      events. The scaffolding protein Na(+)/H(+) exchanger regulatory factor 1 (NHERF1)
      assembles macromolecular signaling complexes and regulates the macromolecular
      assembly, localization, and intracellular trafficking of a number of membrane ion
      transport proteins, receptors, and adhesion/antiadhesion proteins. NHERF1 begins
      with two modular protein-protein interaction domains-PDZ1 and PDZ2-and ends with
      a C-terminal (CT) domain. This CT domain binds to ezrin, which, in turn,
      interacts with cytosekeletal actin. Remarkably, ezrin binding to NHERF1 increases
      the binding capabilities of both PDZ domains. Here, we use deuterium labeling and
      contrast variation neutron-scattering experiments to determine the conformational
      changes in NHERF1 when it forms a complex with ezrin. Upon binding to ezrin,
      NHERF1 undergoes significant conformational changes in the region linking PDZ2
      and its CT ezrin-binding domain, as well as in the region linking PDZ1 and PDZ2,
      involving very long range interactions over 120 A. The results provide a
      structural explanation, at mesoscopic scales, of the allosteric control of NHERF1
      by ezrin as it assembles protein complexes. Because of the essential roles of
      NHERF1 and ezrin in intracellular trafficking in epithelial cells, we hypothesize
      that this long-range allosteric regulation of NHERF1 by ezrin enables the
      membrane-cytoskeleton to assemble protein complexes that control cross-talk and
      regulate the strength and duration of signaling.

PMID- 19591842
TI  - The structural basis of beta-peptide-specific cleavage by the serine protease
      cyanophycinase.
AB  - Cyanophycin, or poly-L-Asp-multi-L-Arg, is a non-ribosomally synthesized peptidic
      polymer that is used for nitrogen storage by cyanobacteria and other select
      eubacteria. Upon synthesis, it self-associates to form insoluble granules, the
      degradation of which is uniquely catalyzed by a carboxy-terminal-specific
      protease, cyanophycinase. We have determined the structure of cyanophycinase from
      the freshwater cyanobacterium Synechocystis sp. PCC6803 at 1.5-A resolution,
      showing that the structure is dimeric, with individual protomers resembling
      aspartyl dipeptidase. Kinetic characterization of the enzyme demonstrates that
      the enzyme displays Michaelis-Menten kinetics with a k(cat) of 16.5 s(-1) and a
      k(cat)/K(M) of 7.5x10(-6) M(-1) s(-1). Site-directed mutagenesis experiments
      confirm that cyanophycinase is a serine protease and that Gln101, Asp172, Gln173,
      Arg178, Arg180 and Arg183, which form a conserved pocket adjacent to the
      catalytic Ser132, are functionally critical residues. Modeling indicates that
      cyanophycinase binds the beta-Asp-Arg dipeptide residue immediately N-terminal to
      the scissile bond in an extended conformation in this pocket, primarily
      recognizing this penultimate beta-Asp-Arg residue of the polymeric chain. Because
      binding and catalysis depend on substrate features unique to beta-linked aspartyl
      peptides, cyanophycinase is able to act within the cytosol without non-specific
      cleavage events disrupting essential cellular processes.

PMID- 19591843
TI  - Structural insights into the protease-like antigen Plasmodium falciparum SERA5
      and its noncanonical active-site serine.
AB  - The sera genes of the malaria-causing parasite Plasmodium encode a family of
      unique proteins that are maximally expressed at the time of egress of parasites
      from infected red blood cells. These multi-domain proteins are unique, containing
      a central papain-like cysteine-protease fragment enclosed between the disulfide
      linked N- and C-terminal domains. However, the central fragment of several
      members of this family, including serine repeat antigen 5 (SERA5), contains a
      serine (S596) in place of the active-site cysteine. Here we report the crystal
      structure of the central protease-like domain of Plasmodium falciparum SERA5,
      revealing a number of anomalies in addition to the putative nucleophilic serine:
      (1) the structure of the putative active site is not conducive to binding
      substrate in the canonical cysteine-protease manner; (2) the side chain of D594
      restricts access of substrate to the putative active site; and (3) the S(2)
      specificity pocket is occupied by the side chain of Y735, reducing this site to a
      small depression on the protein surface. Attempts to determine the structure in
      complex with known inhibitors were not successful. Thus, despite having revealed
      its structure, the function of the catalytic domain of SERA5 remains an enigma.

PMID- 19591845
TI  - The robustness of keystone indices in food webs.
AB  - Species that have outstanding importance in the functioning of a community are
      called keystone species. Network indices are increasingly used to identify them,
      e.g. for conservation biological purposes. The problem is that the calculation of
      these indices is based on the particular network model of the studied food web,
      which can include network construction errors. For example, additional,
      unnecessary trophic links can be built in, or, to the contrary, functional links
      can be left out. What is the effect of such errors on the result of network
      analysis, e.g. the centrality values of species? Can you rely on the importance
      rank of species that you calculated? We developed a robustness measure (R) for
      network indices to answer these questions. R is proportional to the likeliness
      that the importance rank of nodes in the given network according to a given index
      would not change due to possible errors in network construction. For calculating
      R, first the maximum expected error (P) has to be computed which represents the
      potential range of error in estimating the keystone index in question. Basically,
      R is calculated by comparing P to the keystone indices of species to assess the
      reliability of the importance rank of species based on the network model. We
      calculated the robustness of 13 different structural indices in 26 food webs of
      different size to test the P and R values. We found that fragmentation indices
      and the number of dominated nodes can be characterized by quite low R values,
      while betweenness, topological importance, keystoneness and mixed trophic impact
      have high R values, which means that they are relatively more reliable for
      assessing the importance rank of species in an uncertain network model. However,
      as R was found to be very variable, depending on the topology of a given network,
      a detailed description is provided for performing the actual calculations case-by
      case.

PMID- 19591844
TI  - 10-A cryoEM structure and molecular model of the Myriapod (Scutigera) 6x6mer
      hemocyanin: understanding a giant oxygen transport protein.
AB  - Oxygen transport in Myriapoda is maintained by a unique 6x6mer hemocyanin, that
      is, 36 subunits arranged as six hexamers (1x6mers). In the sluggish diplopod
      Spirostreptus, the 1x6mers seem to operate as almost or fully independent
      allosteric units (h approximately 1.3; P(50) approximately 5 torr), whereas in
      the swift centipede Scutigera, they intensively cooperate allosterically (h
      approximately 10; P(50) approximately 50 torr). Here, we show the chemomechanical
      basis of this differential behavior as deduced from hybrid 6x6mer structures,
      obtained by single-particle cryo-electron microscopy of the Scutigera 6x6mer
      (10.0 A resolution according to the 0.5 criterion) and docking of homology
      modeled subunits from Scutigera and two diplopods, Spirostreptus and Polydesmus.
      The Scutigera 6x6mer hemocyanin is a trigonal antiprism assembled from six
      smaller trigonal antiprisms (1x6mers), thereby exhibiting D3 point group
      symmetry. It can be described as two staggered 3x6mers or three oblique 2x6mers.
      Topologically, the 6x6mer is subdivided into six subunit zones, thereby
      exhibiting a mantle (24 subunits) and a core (12 subunits). The six hexamers are
      linked by 21 bridges, subdivided into five types: two within each 3x6mer and
      three between both 3x6mers. The molecular models of the 6x6mer reveal intriguing
      amino acid appositions at these inter-hexamer interfaces. Besides opportunities
      for salt bridges, we found pairs of carboxylate residues for possible bridging
      via a Ca(2+) or Mg(2+) ion. Moreover, we detected histidine clusters, notably in
      Scutigera, allowing us to advance hypotheses as to how the hexamers are
      allosterically coupled in centipede hemocyanin and why they act more
      independently in diplopod hemocyanin.

PMID- 19591846
TI  - Structural relatedness via flow networks in protein sequence space.
AB  - A novel approach for evaluation of sequence relatedness via a network over the
      sequence space is presented. This relatedness is quantified by graph theoretical
      techniques. The graph is perceived as a flow network, and flow algorithms are
      applied. The number of independent pathways between nodes in the network is shown
      to reflect structural similarity of corresponding protein fragments. These
      results provide an appropriate parameter for quantitative estimation of such
      relatedness, as well as reliability of the prediction. They also demonstrate a
      new potential for sequence analysis and comparison by means of the flow network
      in the sequence space.

PMID- 19591847
TI  - Optimal defense strategy against herbivory in plants: conditions selecting for
      induced defense, constitutive defense, and no-defense.
AB  - To examine the conditions selecting for induced defense, constitutive defense,
      and no-defense, we developed a model of plant defense strategy against herbivory.
      In the model, a plant consists of two modules between which signal inducing
      defense compounds can be translocated. We assume three strategies: plants produce
      defense compounds responding to herbivory (induced defense), they have the
      compounds beforehand (constitutive defense), and they never produce the compounds
      (no-defense). We found that no-defense is optimal if the amount of biomass lost
      due to herbivory is small because of the growth cost of having defense compounds.
      The constitutive defense is optimal if the amount of biomass lost is not so small
      and the probability of herbivory is high. If the biomass loss is not so small but
      the probability of herbivory is low, the induced defense or no-defense is
      optimal. When the induced defense is optimal, the probability of herbivory
      necessarily increases in plants once herbivory has occurred. If the probability
      stays the same, no-defense is optimal. Thus, the behavior of herbivores, i.e.,
      whether they remain around a plant and attack it repeatedly, affects the
      evolution of the induced defense.

PMID- 19591849
TI  - Dopamine D1 receptor activation induces tau phosphorylation via cdk5 and GSK3
      signaling pathways.
AB  - Increasing evidence is demonstrating that drugs affecting dopamine levels in the
      brain induce cytoskeletal modifications. These evolving changes may impact
      neuronal synaptic plasticity as cytoskeletal constituents are involved in the
      maintenance of dendritic processes, and any alterations in their stability could
      influence major cellular compartments of neurons, such as dendrites, spines and
      synapses. Here, we describe a molecular chain of events that links dopamine D1
      receptor activation to hyperphosphorylation of the microtubule-associated protein
      tau, which is normally involved in microtubules stabilization. We show, in SK-N
      MC cells and rat striatal sections, that phosphorylation of tau at serines 199
      202 and 214 appears to be mediated through activation of calcium-dependent
      intracellular mechanism, subsequent to D1 receptor-induced cAMP-dependent protein
      kinase A (PKA). We demonstrate, using pharmacological tools, that PKA activation
      causes increase of calcium levels, leading to cyclin-dependent kinase 5
      activation by calpain proteolysis of p35 to p25 and glycogen synthase kinase
      3beta activation by its phosphorylation at tyrosine 216. The D2 receptor agonism
      or lowering cAMP levels has no effect in our experimental settings. Moreover, we
      do not observe any association between phosphorylated tau and cellular damage.
      These data unravel novel mechanisms of tau hyperphosphorylation during G-protein
      coupled receptor activation and are the first to show that stimulation of D1
      receptors could have a profound influence on the neuronal cytoskeletal
      constituent tau.

PMID- 19591848
TI  - Reproductive age-related changes in the blood brain barrier: expression of IgG
      and tight junction proteins.
AB  - We previously demonstrated that there is a significantly greater transfer of
      intravenously-injected Evan's blue dye into the forebrain of acyclic
      (reproductive senescent) females compared to young adult females, indicating that
      blood brain barrier permeability is compromised in the reproductive senescent
      forebrain. The present study examined brain IgG expression and microvessel tight
      junction proteins to assess ovarian age-related changes in microvascular
      permeability, and further compared young and senescent females with age-matched
      males to distinguish changes attributable to age and reproductive senescence.
      Blood brain barrier breakdown are often associated with increased extravasation
      of plasma proteins and high levels of immunoglobulin G (IgG) in brain. In the
      present study, IgG expression was dramatically increased in the hippocampus and
      thalamus, but not the hypothalamus of reproductive senescent females compared to
      young adult females. In males, IgG expression was increased in all these regions
      in middle-aged animals (aged-matched to senescent females) as compared to young
      males (age-matched to the young adult females). Furthermore, the proportion of
      hippocampal microvessels with perivascular IgG immunoreactivity was significantly
      greater in reproductive senescent females as compared to young adult females,
      while middle-aged males and young adult males did not differ. The tight junctions
      between adjacent microvascular endothelial cells regulated by transmembrane
      proteins such as claudin-5 and occludin play a critical role in maintaining the
      blood brain barrier integrity. Increased hippocampal IgG expression in senescent
      females was paralleled by poor junctional localization of the tight junction
      protein claudin-5 in hippocampal microvessels. However, there was no difference
      in hippocampal claudin-5 localization between young adult and middle-aged males,
      indicating that dysregulation of this junctional protein was associated with
      ovarian aging. Parallel studies in human brain microvessels also revealed age
      dependent disruption in claudin-5 distribution in post-menopausal women compared
      to pre-menopausal women. Collectively, these data support the hypothesis that
      constitutive loss of barrier integrity in the forebrain during reproductive
      senescence may be due, in part, to the selective loss of tight junction proteins
      in endothelial junctions.

PMID- 19591850
TI  - Orexin/hypocretin is necessary for context-driven cocaine-seeking.
AB  - Orexin/hypocretin signaling at the orexin 1 receptor (OX(1)R) has recently been
      implicated in addiction and relapse. We examined the role of the orexin system in
      cocaine-seeking elicited by a drug-associated context following abstinence or
      extinction from chronic cocaine self-administration. Male Sprague-Dawley rats
      self-administered cocaine in 2-h sessions for 10 days, followed by extinction
      training or extended abstinence in the home cage. The OX(1)R antagonist SB-334867
      (SB; 10, 20, or 30 mg/kg, i.p.) was administered prior to re-exposure to the
      cocaine self-administration environment. We found that pretreatment with SB
      significantly attenuated cocaine-seeking when rats were placed back into the self
      administration environment following either 1 day or 2 weeks of abstinence (no
      extinction), or following extinction of cocaine-seeking in an alternative
      environment (distinct from the training environment). These results indicate that
      orexin signaling at OX(1)R is critical for conditioned cocaine-seeking elicited
      by a drug-associated context, following either extinction or abstinence.

PMID- 19591851
TI  - Beating the boojum: comparative approaches to the neurobiology of social
      behavior.
AB  - Neuropeptides coordinate complex social behaviors important to both basic and
      applied science. Understanding such phenomena requires supplementing the powerful
      tools of behavioral neuroscience with less conventional model species and more
      rigorous evolutionary analyses. We review studies that use comparative methods to
      examine the roles of vasopressin and oxytocin in mammalian social behavior. We
      find that oxytocin and vasopressin receptor distributions are remarkably variable
      within species. Studies of socially monogamous prairie voles reveal that
      pronounced individual differences in spatial memory structures (retrosplenial
      cortex and hippocampus) are better predictors of social and sexual fidelity than
      are areas known to regulate pairbonding directly, a pattern that seems to be
      mediated by the contributions of the neuropeptides to space use in natural
      settings. We next examine studies of individual and species differences in cis
      regulatory regions of the avpr1a locus. While individual differences in social
      behaviors are linked to length of a microsatellite at the avpr1a locus,
      phylogenetic analyses reveal that the presence or absence of a microsatellite
      does not explain major differences between species. There seems to be no simple
      relationship between microsatellite length and behavior, but rather
      microsatellite length may be a marker for more subtle sequence differences
      between individuals. Lastly, we introduce the singing mouse, Scotinomys teguina,
      whose neuropeptide receptor distributions and unique natural history make it an
      exciting new model for mammalian vocalization and social cognition. The findings
      demonstrate how taxonomic and conceptual diversity provide a broader basis for
      understanding social behavior and its dysfunction.

PMID- 19591853
TI  - Pharmacological characterization of standard analgesics on mechanical allodynia
      in streptozotocin-induced diabetic rats.
AB  - The present study was designed to investigate the anti-allodynic effects of
      current analgesic agents, such as pregabalin, amitriptyline, mexiletine,
      morphine, and diclofenac, in a rat model of streptozotocin (STZ)-induced diabetic
      neuropathy. Diabetic rats developed a sustained decrease in withdrawal threshold
      response to the von Frey test within 8 weeks after a single injection of STZ (45
      mg/kg, i.v.). The anti-allodynic effects of analgesic agents were examined after
      a single oral or subcutaneous administration at 3 and 7 weeks after beginning of
      STZ-treatment. Pregabalin (3-30 mg/kg, p.o.), an antiepileptic agent, dose
      dependently blocked the mechanical allodynia in rats treated both at 3 and 7
      weeks. Mexiletine (10-100 mg/kg, p.o.), a sodium channel blocker, dose
      dependently ameliorated mechanical allodynia in rats treated at 3 weeks; however,
      the efficacy was diminished at 7 weeks. Morphine (1-10 mg/kg, s.c.) was effective
      in rats treated at 3 weeks; however, it was ineffective at 7 weeks. Conversely,
      an antidepressant amitriptyline (0.3-3 mg/kg, p.o.) improved mechanical allodynia
      in rats treated at 7 weeks, whereas it was ineffective at 3 weeks. Diclofenac, a
      non-steroidal anti-inflammatory drug, was ineffective at both time points. These
      results demonstrate that, except for diclofenac, the standard analgesic agents
      tested can effectively alleviate the mechanical allodynia seen in STZ-induced
      diabetic neuropathy. Their efficacies varied depending on the duration of the
      diabetic condition, suggesting that temporal changes in pharmacodynamic factors
      could affect the responsiveness of this model to analgesic agents.

PMID- 19591852
TI  - Salvinorin A and derivatives: protection from metabolism does not prolong short
      term, whole-brain residence.
AB  - Salvinorin A (SA) is a potent kappa opioid agonist with a brief duration of
      action. Consistent with this, our previous positron emission tomography (PET)
      studies of carbon-11 labeled SA showed that brain levels decrease rapidly after
      intravenous administration. SA is rapidly metabolized, giving the much less
      potent salvinorin B (SB), which is presumed to be responsible in part for SA's
      brief duration of action. To test this, we labeled the metabolically stable
      methyl ester of SA and SB with carbon-11 and compared their pharmacokinetics by
      PET imaging after intravenous administration to baboons. Labeling of salvinorin B
      ethoxymethyl ether (EOM-SB), a derivative with greater potency and resistance to
      metabolism, provided an additional test of the role of metabolism in brain
      efflux. Plasma analysis confirmed that SB and EOM-SB exhibited greater metabolic
      stability than SA. However, the three compounds exhibited very similar
      pharmacokinetics in brain, entering and exiting rapidly. This suggests that
      metabolism is not solely responsible for the brief brain residence time of SA. We
      determined that whole-brain concentrations of EOM-SB declined more slowly than SA
      after intraperitoneal administration in rodents. This is likely due to a
      combination in EOM-SB's increased metabolic stability and its decreased plasma
      protein affinity. Our results suggest that protecting salvinorin A derivatives
      from metabolism will prolong duration of action, but only when administered by
      routes giving slow absorption.

PMID- 19591854
TI  - Associative reinstatement: a novel approach to assessing associative memory in
      patients with unilateral temporal lobe excisions.
AB  - We investigated whether unilateral medial temporal lobe (MTL) damage disrupts
      associative reinstatement, which represents the gain in item memory when the
      studied associative information is reinstated at retrieval. We were interested to
      see whether associative reinstatement relies on the same relational binding
      operations that support other types of associative memory (associative
      identification and recollection) thought to be subserved by the MTL. In addition,
      we examined whether such damage affects the different types of associative memory
      to a greater extent than item memory and item familiarity, and whether a
      different pattern is seen in patients with language dominant relative to non
      dominant temporal lobe resection when the studied material consists of verbal
      information. To do so, we used a word pair recognition paradigm composed of two
      tasks: (1) a pair recognition task that provides measures of associative
      reinstatement and item memory, and (2) an associative identification recognition
      task that provides a measure of associative identification memory. Estimates of
      item familiarity and recollection were derived from performance on both tasks
      using a variant of the process-dissociation procedure. Our results showed that
      associative reinstatement, like other types of associative memory measures, was
      impaired in patients with unilateral resection, irrespective of the side of
      damage. Item familiarity, however, was impaired solely following language
      dominant resection. The lack of a laterality effect in our relational measures
      was likely due to using an encoding task that promoted formation of both verbal
      and visual associations, whereas item-based familiarity could rely exclusively on
      verbal operations. We propose that associative reinstatement provides a sensitive
      measure of relational memory that is less dependent on strategic processing and
      therefore more appropriate for evaluating MTL function in patients.

PMID- 19591855
TI  - Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression
      and increases neuronal vulnerability to glutamate.
AB  - Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially
      as a heat stabilizer, agricultural pesticide and component of antifouling paints.
      In this study, we investigated the effect of long-term exposure to endogenous
      levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were
      exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of
      neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT.
      Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate
      receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and
      GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA
      receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+
      influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx
      was increased in TBT-treated neurons. Consistent with this, neurons became more
      susceptible to glutamate toxicity as a result of long-term exposure to TBT and
      this susceptibility was abolished by an antagonist of GluR2-lacking AMPA
      receptor. Thus, it is suggested that long-term exposure to endogenous levels of
      TBT induces a decrease of GluR2 protein, causing neurons become more susceptible
      to glutamate toxicity.

PMID- 19591856
TI  - HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active
      ribotoxin deoxynivalenol.
AB  - HuR/Elav-like RNA binding protein 1 (ELAVL1) positively regulates mRNA stability
      of AU-rich elements (ARE)-containing transcript such as pro-inflammatory
      cytokines. Ribotoxic stresses can trigger the production of pro-inflammatory
      mediators by enhancing mRNA stability and the transcriptional activity. We
      investigated the effects of ribotoxin deoxynivalenol (DON) on HuR translocation
      and its involvement in the regulation of the pro-inflammatory interleukin-8 (IL
      8) mRNA stability. Exposure to the muco-active DON induced nuclear export of both
      endogenous and exogenous HuR RNA binding protein in human intestinal epithelial
      cells. Moreover, the interference with HuR protein production suppressed
      ribotoxic DON-induced IL-8 secretion and its mRNA stability. Cytoplasmic HuR
      protein interacted with IL-8 mRNA and the complex stabilization was due to the
      presence of 3'-untranslated region of the transcript. Partly in terms of IL-8
      modulating transcription factors, HuR protein was demonstrated to be positively
      and negatively associated with DON-induced early growth response gene 1 (EGR-1)
      and activating transcription factor 3 (ATF3), respectively. HuR was a critical
      mechanistic link between ribotoxic stress and the pro-inflammatory cytokine
      production, and may have a broader functional significance with regard to mucosal
      insults since ribotoxic stress responses are also produced upon interactions with
      the diverse environment of gut.

PMID- 19591857
TI  - Epidemiological, clinical and therapeutic aspects of Bothrops asper bites.
AB  - Bothrops asper inflicts the majority of snakebites in Central America and in the
      northern regions of South America, mostly affecting young agricultural workers in
      rural settings. This species is capable of provoking severe envenomings
      associated with local and systemic manifestations. The main clinical features
      are: local edema, ecchymoses, blisters, dermonecrosis, myonecrosis,
      defibrinogenation, thrombocytopenia, systemic bleeding, hypotension and renal
      alterations. In addition, soft-tissue infection, acute renal failure,
      compartmental syndrome, central nervous system hemorrhage and, in pregnant women,
      abortion, fetal wastage and abruptio placentae have been described as
      complications. Intravenous administration of antivenom constitutes the mainstay
      in the therapy. Antivenoms composed of either whole IgG or F(ab')(2) fragments,
      manufactured in Brazil, Colombia, Costa Rica and Mexico, have been tested in
      controlled clinical trials, and rational protocols for antivenom administration
      have been developed. In addition to antivenom therapy, a number of ancillary
      interventions are recommended in the treatment of B. asper bites.

PMID- 19591858
TI  - Double lethal coconut crab (Birgus latro L.) poisoning.
AB  - We report a double lethal coconut crab Birgus latro L. poisoning in New
      Caledonia. Both patients died after showing gastro-intestinal symptoms, major
      bradycardia with marked low blood pressure, and finally asystolia. Both had
      significative hyperkaliemia, suggesting a digitaline-like substance intoxication.
      Traditional knowledge in the Loyalty Islands relates coconut crab toxicity to the
      consumption of the Cerbera manghas fruit by the crustacean. Elsewhere previous
      descriptions of human poisoning with the kernel of fruits of trees belonging to
      the genus Cerbera, known to contain cardiotoxic cardenolides, appear to be very
      similar to our cases. Cardenolides assays were performed on patient's serum
      samples, fruit kernel and on the crustacean guts, which lead us to suppose these
      two fatal cases were the result of a neriifolin intoxication, this toxin having
      been transmitted through the coconut crab.

PMID- 19591859
TI  - Space-saving advantage of an inverted retina.
AB  - Vertebrate eyes are of the simple or camera type with a single optical system
      that creates an image on the retina in the back of the eye. There, the visual
      information is encoded as nervous signals by photoreceptors, processed by retinal
      neurons, and then sent to the brain via the optic nerve. Surprisingly at first
      sight, the retinal neurons are located between the lens and the light-sensitive
      parts of the photoreceptors. The tissue scatters some light, which leads to loss
      of light and image blur. The inverted retina has, therefore, long been regarded
      as inferior. Here, we provide evidence that the inverted retina actually is a
      superior space-saving solution, especially in small eyes. The inverted retina has
      most likely facilitated the evolution of image-forming eyes in vertebrates, and
      it still benefits especially small and highly visual species.

PMID- 19591860
TI  - Education and training in physical activity research and practice.
AB  - Despite rapid growth in resources devoted to physical activity promotion, the
      public health capacity to address physical inactivity is insufficient. Too few
      public health practitioners have the necessary skills to implement and evaluate
      evidence-based physical activity interventions, and schools of public health
      typically do not have adequate course content in physical activity. This
      commentary discusses the types of initiatives needed to improve the education and
      training of physical activity practitioners and researchers to effectively
      address one of the 21st century's greatest health problems--an inactive
      lifestyle.

PMID- 19591861
TI  - Promoting physical activity and reducing climate change: opportunities to replace
      short car trips with active transportation.
AB  - Automobile use is a significant contributor to climate change, local air
      pollution, pedestrian injuries and deaths, declines in physical activity and
      obesity. A significant proportion of car use is for short trips that can
      relatively easily be taken with active transportation options--walking or cycling
      -or with public transportation. In this commentary, we review a number of
      immediate, practical opportunities to implement policies and programs that reduce
      short car trips and increase active transportation.

PMID- 19591862
TI  - Structural analysis of toxic volkensin, a type 2 ribosome inactivating protein
      from Adenia volkensii Harm (kilyambiti plant): molecular modeling and surface
      analysis by computational methods and limited proteolysis.
AB  - Volkensin, isolated from Adenia volkensii, is one of the most toxic type 2
      ribosome-inactivating protein (RIP), exerting its biological function by
      inhibiting protein synthesis. Despite the high sequence identity with type 2
      RIPs, including ricin, volkensin shows interesting peculiar properties. In this
      work a computational model building of volkensin was performed. The volkensin
      electrostatic potential charge distribution, the hydrophobic profile and the
      surface topology analyses were also carried out to aid the understanding of
      structure-function relationships of this potent toxin. Volkensin surface topology
      was probed by applying a limited proteolysis approach with the aim to gain
      insights into volkensin conformational features.

PMID- 19591863
TI  - Brain lesions comprised of aluminum-rich cells that lack microtubules may be
      associated with the cognitive deficit of Alzheimer's disease.
AB  - A recent longitudinal study described an inducible rodent model for age-related
      cognitive deterioration. This model was produced by chronically feeding rats
      aluminum, from age 12 months onwards, in measured amounts equivalent to total
      aluminum levels ingested by Americans from their food, beverages and aluminum
      additives. The rats performed a hippocampal-dependent spatial memory
      discrimination task weekly throughout middle age and old age. One-third of the
      rats attained significantly lower mean performance scores in old age than middle
      age, in an aluminum dose-dependent manner, and exhibited behavioral signs
      observed in dementia. The present study used histological and immunohistochemical
      techniques to identify neuropathological difference between brains of rats that
      showed cognitive deterioration and the cognitively intact controls. Most aged rat
      brains had large numbers of aluminum-loaded pyramidal cells in their entorhinal
      cortex and temporal association cortex but the cognitively deteriorated rats had
      threefold more such cells than controls (p<0.01). A distinguishing feature was
      that all brains of the cognitively deteriorated rats, and none of controls, had
      at least one substantial hippocampal lesion that consisted of aluminum-rich
      microtubule-depleted pyramidal cells with shriveled processes, and loss of
      synapse density. Corticolimbic sections from brains of humans with Alzheimer's
      disease also showed neuropathology consistent with this type of damage. The
      evidence suggests bioavailable aluminum gradually accumulates in cortical and
      limbic regions of susceptible subjects' brains, eventually producing hippocampal
      lesions consisting of dysfunctional aluminum-rich microtubule-depleted pyramidal
      cells with damaged neurites and synapse loss. These lesions expand over time,
      disrupting afferent and efferent hippocampal circuitry with the development of
      clinically overt dementia.

PMID- 19591864
TI  - Mangifera indica L. extract attenuates glutamate-induced neurotoxicity on rat
      cortical neurons.
AB  - Overstimulation of ionotropic glutamate receptors causes excitotoxic neuronal
      death contributing to neurodegenerative disorders. Massive influx of calcium in
      excitotoxicity provokes alterations in the membrane potential of mitochondria and
      increases the production of reactive oxygen species. Here we report that
      Mangifera indica L. extracts (MiE) prevent glutamate-induced excitotoxicity in
      primary cultured neurons of the rat cerebral cortex. To evaluate the effects of
      MiE on excitotoxicity, cells were stimulated with L-glutamic acid (50 microM; 10
      min) alone or in the presence of MiE. Maximal protection (56%) was obtained with
      2.5 microg/mL of MiE. In turn, we measured the effects of MiE on excitotoxic
      induced oxidative stress and mitochondrial depolarization by fluorimetry using
      5,6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and
      tetramethylrhodamine, respectively. Both parameters were effectively reduced by
      MiE at concentrations which showed neuroprotection. Mangiferin, an antioxidant
      polyphenol which is a major component of MiE, was also effective in preventing
      neuronal death, oxidative stress and mitochondrial depolarization. Maximal
      protection (64%) was obtained at 12.5 microg/mL of mangiferin which also
      attenuated oxidative stress and mitochondrial depolarization at the
      neuroprotective concentrations. Together, these results indicate that MiE is an
      efficient neuroprotector of excitotoxic neuronal death, indicates that mangiferin
      carries a substantial part of the antioxidant and neuroprotective activity of
      MiE, and that this natural extract has therapeutic potential to treat
      neurodegenerative disorders.

PMID- 19591866
TI  - A structure-dynamic approach to cortical organization: number of paths and
      accessibility.
AB  - A structure-dynamic approach to cortical systems is reported which is based on
      the number of paths and the accessibility of each node. The latter measurement is
      obtained by performing self-avoiding random walks in the respective networks, so
      as to simulate dynamics, and then calculating the entropies of the transition
      probabilities for walks starting from each node. Cortical networks of three
      species, namely cat, macaque and humans, are studied considering structural and
      dynamical aspects. It is verified that the human cortical network presents the
      highest accessibility and number of paths (in terms of z-scores). The correlation
      between the number of paths and accessibility is also investigated as a mean to
      quantify the level of independence between paths connecting pairs of nodes in
      cortical networks. By comparing the cortical networks of cat, macaque and humans,
      it is verified that the human cortical network tends to present the largest
      number of independent paths of length larger than four. These results suggest
      that the human cortical network is potentially the most resilient to brain
      injures.

PMID- 19591867
TI  - Measuring multiple spike train synchrony.
AB  - Measures of multiple spike train synchrony are essential in order to study issues
      such as spike timing reliability, network synchronization, and neuronal coding.
      These measures can broadly be divided in multivariate measures and averages over
      bivariate measures. One of the most recent bivariate approaches, the ISI
      distance, employs the ratio of instantaneous interspike intervals (ISIs). In this
      study we propose two extensions of the ISI-distance, the straightforward averaged
      bivariate ISI-distance and the multivariate ISI-diversity based on the
      coefficient of variation. Like the original measure these extensions combine many
      properties desirable in applications to real data. In particular, they are
      parameter-free, time scale independent, and easy to visualize in a time-resolved
      manner, as we illustrate with in vitro recordings from a cortical neuron. Using a
      simulated network of Hindemarsh-Rose neurons as a controlled configuration we
      compare the performance of our methods in distinguishing different levels of
      multi-neuron spike train synchrony to the performance of six other previously
      published measures. We show and explain why the averaged bivariate measures
      perform better than the multivariate ones and why the multivariate ISI-diversity
      is the best performer among the multivariate methods. Finally, in a comparison
      against standard methods that rely on moving window estimates, we use single-unit
      monkey data to demonstrate the advantages of the instantaneous nature of our
      methods.

PMID- 19591865
TI  - Primary brain targets of nerve agents: the role of the amygdala in comparison to
      the hippocampus.
AB  - Exposure to nerve agents and other organophosphorus acetylcholinesterases used in
      industry and agriculture can cause death, or brain damage, producing long-term
      cognitive and behavioral deficits. Brain damage is primarily caused by the
      intense seizure activity induced by these agents. Identifying the brain regions
      that respond most intensely to nerve agents, in terms of generating and spreading
      seizure activity, along with knowledge of the physiology and biochemistry of
      these regions, can facilitate the development of pharmacological treatments that
      will effectively control seizures even if administered when seizures are well
      underway. Here, we contrast the pathological (neuronal damage) and
      pathophysiological (neuronal activity) findings of responses to nerve agents in
      the amygdala and the hippocampus, the two brain structures that play a central
      role in the generation and spread of seizures. The evidence so far suggests that
      exposure to nerve agents causes significantly more damage in the amygdala than in
      the hippocampus. Furthermore, in in vitro brain slices, the amygdala generates
      prolonged, seizure-like neuronal discharges in response to the nerve agent soman,
      at a time when the hippocampus generates only interictal-like activity. In vivo
      experiments are now required to confirm the primary role that the amygdala seems
      to play in nerve agent-induced seizure generation.

PMID- 19591868
TI  - Three-way matrix analysis, the MUSIC algorithm and the coupled dipole model.
AB  - The inverse problem of multi-channel MEG/EEG data is considered as a parameter
      estimation problem. The stability of the solution of the inverse problem, which
      decreases with the number of included dipoles, can be improved by either adding
      constraints to the model parameters, or by adding more data of related data sets.
      The latter approach was taken by Bijma et al. [Bijma F, de Munck JC, Bocker KBE,
      Huizenga HM, Heethaar RM. The coupled dipole model: an integrated model for
      multiple MEG/EEG data sets. NeuroImage 2004;23(3):890-904; Bijma F, de Munck JC,
      Huizenga HM, Heethaar RM, Nehorai A. Simultaneous estimation and testing in
      multiple MEG data sets. IEEE Trans SP 2005;53(9):3449-60] by introducing coupling
      matrices that link dipole parameters and source time functions of different data
      sets. Here, the theoretical foundations of the coupled dipole model are explored
      and the MUSIC algorithm is generalised to the analysis of multiple related data
      sets. Similar to the MUSIC algorithm, the number of sources and the number of
      constraints are derived from the data by considering the minimum possible
      residual error as a function of the number of sources and constraints. However,
      contrary to the MUSIC algorithm, where the minimum residual error can be obtained
      from an SVD analysis of a two-way data matrix, here we deal with multiple data
      sets and therefore three-way matrix analysis is used. From a simulation study it
      appears that the number of sources and constraints can be clearly determined from
      a generalised SVD analysis. The generalisation of the MUSIC algorithm to three
      way data gives reasonable estimates of the dipole parameters. These results can
      be used in the simultaneous analysis of MEG/EEG data of multiple subjects,
      multiples data sets of the same subject or models where subsequent trials of data
      show habituation effects.

PMID- 19591869
TI  - An objective measurement of locomotion behavior for hemiparkinsonian cynomolgus
      monkeys.
AB  - Both clinical rating scales and objective locomotion measurement are critical
      evaluation for primate models of Parkinson's disease. Video image analysis system
      which has been widely used for objective measurement of locomotion behavior for
      systemic models has rarely been applied to hemiparkinsonian primate model. In
      this study, a video image analysis system provided by Vigie Primates software was
      used to assess the locomotion behavior of MPTP hemi-lesioned parkinsonian
      cynomolgus monkeys by intracarotid infusion. Regardless the presence of only
      hemilateral abnormal movement, this video image analysis system was sensitive
      enough to demonstrate a significant difference between normal and MPTP hemi
      lesioned animal on several aspects of motor behavior depicted by this software,
      including quantity of movement, duration spent in activity and count of burst
      activity. Specifically, a newly introduced ratio of duration/count for every type
      of movements was a sensitive parameter to objectively measure the changes of
      locomotion behavior in MPTP hemi-lesioned parkinsonian primates. As a result, the
      ratio of duration/count for the middle activity was decreased and the ratio of
      duration/count for the freezing activity was increased in MPTP hemi-lesioned
      animals, which correlated well with clinical rating scores. Our results support
      that video image analysis system would be a sensitive objective measurement of
      locomotion behavior for hemi-lesioned parkinsonian monkeys.

PMID- 19591870
TI  - Pulse-coupled neuron models as investigative tools for musical consonance.
AB  - We investigate the mode locking properties of simple dynamical models of pulse
      coupled neurons to two tones, i.e., simple musical intervals. A recently proposed
      nonlinear synchronization theory of musical consonance links the subjective
      ranking from consonant to dissonant intervals to the universal ordering of
      robustness of mode locking ratios in forced nonlinear oscillators. The theory was
      illustrated using two leaky integrate-and-fire neuron models with mutual
      excitatory coupling, with each neuron firing at one of the two frequencies in the
      musical interval. We show that the ordering of mode locked states in such models
      is not universal, but depends on coupling strength. Further, unless the coupling
      is weak, the observed ratio of firing frequencies is higher than that of the
      input tones. We finally explore generic aspects of a possible synchronization
      theory by driving the model neurons with sinusoidal forcing, leading to down
      converted, more realistic firing rates. This model exhibits one-to-one
      entrainment when the input frequencies are in simple ratios. We also consider the
      robustness to the presence of noise that is present in the neural firing
      activity. We briefly discuss agreements and discrepancies between predictions
      from this theory and physiological/psychophysical data, and suggest directions in
      which to develop this theory further.

PMID- 19591871
TI  - Rapid identification of myxoma virus variants by long-range PCR and restriction
      fragment length polymorphism analysis.
AB  - A long-range PCR method directed at the Myxoma virus (MV) left hand and right
      hand terminal inverted repeats (TIRs) for rapid amplification of genomic DNA and
      MV isolate differentiation by restriction fragment length polymorphism (RFLP)
      analysis is described. The efficacy of this method was tested by comparing the
      results from full genome RFLPs with those from TIRs amplified separately using
      reference strain Lausanne (Lu) and a field MV strain characterised previously for
      its virulence in rabbits. The usefulness of this method was also demonstrated by
      amplifying MV DNA directly from the eyelid tissue of an infected rabbit and
      comparative RFLP analysis with respect to Lu. The results proved the long-range
      PCR technique to be a simple highly efficient method for identifying mutations
      between MV genomes by RFLP analyses of the amplified TIRs and may be used in
      future studies to identify variable regions for phylogenetic studies.

PMID- 19591872
TI  - Purification of cell culture-derived influenza virus A/Puerto Rico/8/34 by
      membrane-based immobilized metal affinity chromatography.
AB  - The presented study focuses on the feasibility of immobilized metal affinity
      chromatography for purification of Madin Darby canine kidney cell culture-derived
      influenza virus particles. Therefore, influenza virus A/Puerto Rico/8/34 was
      screened for adsorption to different transition metal ions attached to
      iminodiacetic acid. Subsequently, capturing of the same virus strain using zinc
      modified iminodiacetic acid membrane adsorbers was characterized regarding viral
      recoveries, host cell nucleic acid and total protein depletion as well as zinc
      ion-leaching. In addition, the effect of the imidazole proton pump on virus
      stability was studied based on the hemagglutination activity. During adsorption
      in the presence of 1M sodium chloride the majority of virus particles were
      recovered in the product (64% hemagglutination activity). Host cell nucleic acid
      and total protein content were reduced to approximately 7 and 26%, respectively.
      This inexpensive and rapid method was applied reproducibly for influenza virus
      A/Puerto Rico/8/34 preparations on the laboratory scale. However, preliminary
      results with other virus strains indicated clearly a strong strain dependency for
      viral adsorption.

PMID- 19591873
TI  - Development of SYBR green I based one-step real-time RT-PCR assay for the
      detection and differentiation of very virulent and classical strains of
      infectious bursal disease virus.
AB  - A SYBR Green I based one-step real-time reverse transcriptase polymerase chain
      reaction was developed for the detection and differentiation of very virulent
      (vv) and classical strains of infectious bursal disease virus (IBDV). The assay
      showed high PCR efficiency >93% and high reproducibility with coefficient of
      variation less than 0.5%. When tested on characterized IBDV strains, the very
      virulent and classical-specific primers detected accurately only vvIBDV and
      classical IBDV strains, respectively. The diagnostic efficacy of the assay was
      also tested on 140 bursal samples from experimental infection and 37 bursal
      samples from cases suspected of IBD. The assay was able to detect IBDV from
      bursal samples collected at days 3 and 5 post-infection with the vvIBDV strain
      UPM94/273 and the classical IBDV strain D78. The assay was also able to detect
      bursal samples infected dually with D78 and UPM94/273. The melting temperature
      values of the amplification products from the classical and very virulent viral
      infection were statistically significant (P<0.05). The specificity of the assay
      for detecting IBDV from suspected cases was confirmed by sequence analysis of the
      VP2 gene. The assay showed high sensitivity since bursal samples which were
      negative for IBDV were confirmed by virus isolation and PCR amplification. Hence,
      the new assay offers an attractive method for rapid detection of strains of IBDV.

PMID- 19591875
TI  - Concurrent quantitation of the A and D genotypes of hepatitis B virus.
AB  - Hepatitis B virus (HBV) infection is a global health problem associated with
      severe liver disorders. Viral load and HBV genotype affect the clinical outcome,
      guide antiviral therapy and provide long term prognosis for HBV infected
      patients. Various types of detection and quantitation assays are currently in use
      with a different effectiveness. The aim of this study was to develop a method
      that would provide simultaneous identification and quantitation of genotypes A
      and D in a single-tube reaction. Sera from infected patients were analyzed by a
      TaqMan based real time PCR. Optimized reagents were used for HBV DNA quantitation
      while the genotypes A and D were quantified separately by our design of the
      assay. Multiplex real time PCR was achieved and was specific for HBV genotypes A
      and D within a single-tube reaction. Simulation of mixed virus populations was
      identified reproducibly in vitro. Quantitation of these individual genotypes was
      exceptionally reliable, so much so that the sum of individual genotypes was equal
      to the total viral load determined in a separate reaction. Therefore, a
      straightforward, conceptually simple and reliable approach to issues involving
      HBV genotypes A and D is submitted. Identity and exact titer of these genotypes
      in the Caucasian population can now be determined easily.

PMID- 19591874
TI  - Prevalence and multiplicity of cutaneous beta papilloma viruses in plucked hairs
      depend on cellular DNA input.
AB  - In view of the low loads of beta human papillomaviruses in skin samples, amounts
      of cellular DNA used in qualitative PCR may become limiting for virus detection
      and introduce variations in prevalence and multiplicity. This issue was explored
      within the context of a multicentre study and increasing prevalence and
      multiplicity was found with increasing input amounts of cellular DNA extracted
      from hair bulbs. To improve the quality and comparability between different
      epidemiologic studies ideally equal amounts of cellular DNA should be employed.
      When cellular DNA input varies this should be clearly taken into account in
      assessing viral prevalence and multiplicity.

PMID- 19591876
TI  - A latex agglutination test using a recombinant nucleoprotein for detection of
      antibodies against avian influenza virus.
AB  - A latex agglutination test (LAT) was developed for detecting antibodies against
      avian influenza virus. The recombinant avian influenza virus nucleoprotein
      expressed in Escherichia coli was purified, coupled with latex beads, and used as
      an antigen for the LAT. The LAT was capable of detecting anti-avian influenza
      virus antibodies irrespective of the avian-influenza subtype, and in most cases,
      the results correlated with the results of an agar gel precipitation test (AGPT).
      However, in comparison with the AGPT, the LAT could detect the anti-avian
      influenza virus antibodies for a longer period of time after the infection. The
      nonspecific agglutination observed in uninfected chicken sera was resolved by
      pretreating the sera with dried chicken-liver powder for 1 h. The LAT is easy to
      perform, and even after considering the time required for pretreatment of the
      serum, the total time required for obtaining the results is reduced in comparison
      to the time required in the case of the AGPT. This easy and rapid LAT is
      considered to be useful for monitoring avian influenza virus infection in the
      field.

PMID- 19591877
TI  - Dynamics of antiviral-resistant influenza viruses in the Netherlands, 2005-2008.
AB  - In the Netherlands, influenza specific antivirals are used for the therapy of
      influenza in nursing homes and hospitals, for prophylaxis in high risk groups and
      neuraminidase inhibitors are stockpiled as part of pandemic preparedness plans.
      To monitor the antiviral susceptibility profile, human influenza virus isolates
      derived from the Dutch influenza surveillance in 2005-2006 (n=87), 2006-2007
      (n=58) and 2007-2008 (n=128) were analyzed with phenotypic assays and sequencing.
      For adamantanes, a high proportion (>74%) of A(H3N2) viruses had the S31N
      mutation in M2 protein, while variation in the HA(1) region of adamantane
      sensitive viruses suggested that adamantane-sensitive variants were reseeded into
      the Dutch population and re-emerged as drug-sensitive due to M-segment
      reassortment. For neuraminidase inhibitors oseltamivir and zanamivir, 98% of
      types A and B influenza viruses prior to 2007-2008 were sensitive for both,
      whereas 24% of the A(H1N1) viruses obtained in 2007-2008 were oseltamivir
      resistant while retaining sensitivity to zanamivir and adamantanes. Furthermore,
      oseltamivir-resistant A(H1N1) or adamantane-resistant A(H3N2) virus infections
      were not associated with differences in clinical symptoms compared to infections
      with sensitive variants. Our data show the dynamic nature of emergence of drug
      resistant influenza viruses, stressing the need for surveillance of resistance
      trends as part of influenza monitoring programs.

PMID- 19591878
TI  - Inhibition of Junin virus replication by small interfering RNAs.
AB  - Junin virus (JUNV), the etiological agent of the Argentine hemorrhagic fever, has
      a single-stranded RNA genome with ambisense expression which encodes for five
      proteins. In previous works we have demonstrated that the Z arenavirus matrix
      protein represents an attractive target for antiviral therapy. With the aim of
      studying a new alternative therapeutic mechanism, four Z-specific siRNAs (Z1- to
      Z4-siRNAs) were tested showing variable efficacy. The most effective inhibitor
      was Z2-siRNA targeted at the region encompassed by nt 179-197 of Z gene. The
      efficacy of this Z2-siRNA against JUNV was also demonstrated in virus-infected
      cells, by testing infectious virus plaque formation (92.8% JUNV yield reduction),
      viral RNA level or antigen expression, as well as in cells transfected with Z
      specific reporter plasmids (91% reduction in expression of Z-EGFP fusion
      protein). Furthermore, the lack of effect of this Z-siRNA on the expression of
      other JUNV proteins, such as N and GPC, confirmed the specificity of action
      exerted by Z2-siRNA on Z transcript. Thus, the present study represents the first
      report of virus inhibition mediated by RNA interference for a New World
      arenavirus.

PMID- 19591879
TI  - Combination of soluble coxsackievirus-adenovirus receptor and anti-coxsackievirus
      siRNAs exerts synergistic antiviral activity against coxsackievirus B3.
AB  - Coxsackievirus B3 (CVB-3) is a major causative agent of chronic heart muscle
      infections. The present study describes a cell culture system with an ongoing
      virus infection to evaluate two novel inhibitory strategies, either individually
      or combined: (1) RNA interference (RNAi) to degrade cytoplasmatic CVB-3 RNA and
      (2) a vector-delivered soluble variant of the coxsackievirus-adenovirus receptor
      fused to a human immunoglobulin (sCAR-Fc), which inhibits cellular uptake of CVB
      3. Both approaches were capable of inhibiting CVB-3 in persistently infected
      human myocardial fibroblasts. The antiviral effect of a single treatment lasted
      for up to one week and could be extended by repeated applications. Each of the
      single treatments initially reduced the virus titer by approximately 1-log,
      whereas the combination of both approaches resulted in 4-log inhibition and
      retained substantial antiviral activity at later time points, when the effect of
      sCAR-Fc or siRNAs alone had already disappeared. Further analysis revealed that
      sCAR-Fc protects cells from virus-induced lysis but does not diminish the virus
      load. Reduction of the virus titer was only achieved with additional destruction
      of viral RNA by RNAi. Taken together, combination of RNAi and a protein-based
      antiviral strategy was found to result in a strong synergistic inhibition of an
      ongoing virus infection.

PMID- 19591880
TI  - Influence of light at night on murine anxiety- and depressive-like responses.
AB  - Individuals are increasingly exposed to light at night. Exposure to constant
      light (LL) disrupts circadian rhythms of locomotor activity, body temperature,
      hormones, and the sleep-wake cycle in animals. Other behavioural responses to LL
      have been reported, but are inconsistent. The present experiment sought to
      determine whether LL produces changes in affective responses and whether
      behavioural changes are mediated by alterations in glucocorticoid concentrations.
      Relative to conspecifics maintained in a light/dark cycle (LD, 16:8 light/dark),
      male Swiss-Webster mice exposed to LL for three weeks increased depressive-like
      behavioural responses as evaluated by the forced swim test and sucrose anhedonia.
      Furthermore, providing a light escape tube reversed the effects of LL in the
      forced swim test. LL mice displayed reduced anxiety as evaluated by the open
      field and elevated-plus maze. Glucocorticoid concentrations were reduced in the
      LL group suggesting that the affective behavioural responses to LL are not the
      result of elevated corticosterone. Additionally, mice housed in LD with a clear
      tube displayed increased paired testes mass as compared to LL mice. Taken
      together, these data provide evidence that exposure to unnatural lighting can
      induce significant changes in affect, increasing depressive-like and decreasing
      anxiety-like responses.

PMID- 19591881
TI  - Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A
      potential antimalarial target.
AB  - Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme required for folate
      recycling and dTMP synthesis. A cDNA encoding Plasmodium falciparum (Pf) SHMT was
      expressed as a hexa-histidine tagged protein in Escherichia coli BL21-CodonPlus
      (DE3)-RIL. The protein was purified and the process yielded 3.6 mg protein/l cell
      culture. Recombinant His(6)-tagged PfSHMT exhibits a visible spectrum
      characteristic of pyridoxal-5'-phosphate enzyme and catalyzes the reversible
      conversion of l-serine and tetrahydrofolate (H(4)folate) to glycine and 5,10
      methylenetetrahydrofolate (CH(2)-H(4)folate). Steady-state kinetics study
      indicates that His(6)-tagged PfSHMT catalyzes the reaction by a ternary-complex
      mechanism. The sequence of substrate binding to the enzyme was also examined by
      glycine product inhibition. A striking property that is unique for His(6)-tagged
      PfSHMT is the ability to use D-serine as a substrate in the folate-dependent
      serine-glycine conversion. Kinetic data in combination with expression result
      support the proposal of SHMT reaction being a regulatory step for dTMP cycle.
      This finding suggests that PfSHMT can be a potential target for antimalarial
      chemotherapy.

PMID- 19591882
TI  - Molecular cloning and characterization of a T24-like protein in Echinococcus
      multilocularis.
AB  - One tetraspanin, designated as E24, was cloned from a full-length enriched vector
      capping cDNA library of Echinococcus multilocularis metacestode. The amino acid
      sequence and phylogenetic analysis suggested that E24 is a T24-like protein. The
      crucial, functional large extracellular loop (LEL) domain of E24 was expressed
      and characterized using a polyclonal antiserum by Western blot and
      immunohistochemistry. The results showed that anti-recombinant-E24 (anti-recE24)
      antibody can specifically recognize approximately 25 kDa recombinant protein and
      25 kDa cyst-extracted antigen; the germinal layer of both the protoscolex-free
      and protoscolex-formed cysts were intensely labeled by immunofluorescent
      antibody. This study revealed that E24 is an antigenic, germinal layer-located
      protein of E. multilocularis metacestode, implying for its potential in
      diagnostic and vaccine development.

PMID- 19591884
TI  - Virus research--25th anniversary issue. Preface.

PMID- 19591883
TI  - Catalytic and ligand-binding characteristics of Plasmodium falciparum serine
      hydroxymethyltransferase.
AB  - The plant-like, bifunctional dihydrofolate reductase-thymidylate synthase (DHFR
      TS) from malaria parasites has been a good target for drug development.
      Dihydrofolate reductase (DHFR) is inhibited by clinically established
      antimalarials, pyrimethamine and cycloguanil. Thymidylate synthase (TS) is the
      target of potent experimental antimalarials such as 5-fluoroorotate and 1843U89.
      Another enzyme in folate recycling, serine hydroxymethyltransferase (SHMT),
      produces 5,10-methylenetetrahydrofolate which, in many cells, is required for the
      de novo, biosynthesis of thymidine and methionine. Thus, the biochemical
      characterization of malarial SHMT was of interest. The principle, active
      Plasmodium falciparum SHMT (PfSHMT) was expressed in E. coli and purified using
      an N-terminal histidine tag. Unlike the plant enzyme, but like the host enzyme,
      PfSHMT requires the cofactor pyridoxal 5'-phosphate for enzymatic activity. The
      substrate specificities for serine, tetrahydrofolate, and pyridoxal 5'-phosphate
      were comparable to those for SHMT from other organisms. Antifolates developed for
      DHFR and TS inhibited SHMT in the mid-micromolar range, offering insights into
      the binding preferences of SHMT but clearly leaving room for improved new
      inhibitors. As previously seen with P. falciparum DHFR-TS, PfSHMT bound its
      cognate mRNA but not control RNA for actin. RNA binding was not reversed with
      enzyme substrates. Unlike DHFR-TS, the SHMT RNA-protein interaction was not tight
      enough to inhibit translation. Another gene PF14_0534, previously proposed to
      code for an alternate mitochondrial SHMT, was also expressed in E. coli but found
      to be inactive. This protein, nor DHFR-TS, enhanced the catalytic activity of
      PfSHMT. The present results set the stage for developing specific, potent
      inhibitors of SHMT from P. falciparum.

PMID- 19591885
TI  - Effect of the consumption of high energy dense and fortified gruels on energy and
      nutrient intakes of 6-10-month-old Vietnamese infants.
AB  - The aim of this study was to test the ability of two new products, an instant
      infant flour and a food supplement containing amylases, to increase energy and
      micronutrient intakes of infants older than 6 months. Three groups of 48 infants
      were randomly constituted. Infants in groups 1 and 2 consumed at least twice a
      day gruel made either from the instant flour or from the food supplement. Infants
      from the control group received complementary foods prepared in the usual way.
      Each infant was surveyed during a whole day in order to measure feeding
      frequencies and characteristics as well as amounts of the different types of
      complementary foods consumed. Foods consumed by infants in the two experimental
      groups differed considerably in energy, micronutrient density and in consistency
      from the home-made complementary foods. Due to the incorporation of amylases,
      gruels made from the food supplement had a higher energy density, a more
      appropriate consistency and resulted in higher intakes per meal than gruels made
      from instant flour. In comparison with home-made complementary foods, both
      experimental products resulted in significantly higher energy and nutrient
      intakes. The two experimental products appeared to increase sufficiently both
      energy and nutrient intakes of infants to complement their breastmilk intake.

PMID- 19591886
TI  - Who likes it more? Restrained eaters' implicit attitudes towards food.
AB  - Previous work has been unclear as to how restrained eating is related to implicit
      attitudes towards food. The present paper introduces a new variant of the
      affective priming paradigm to measure implicit attitudes towards food among
      restrained and unrestrained eaters, using food pictures as primes and emoticons
      as targets. Results of two studies show that while unrestrained eaters evaluate
      palatable foods more positively than neutral and unpalatable foods, restrained
      eaters do not. In addition, it is shown that restrained eaters have stronger
      evaluations of the negative aspects of palatable food, and this influences their
      food attitudes. Thus, the present findings suggest that restrained eaters'
      chronic goal of dieting impacts their implicit attitude towards food items via
      their perception of the negative aspects of palatable food. These results are
      discussed with regard to the role of attitudes in the regulation of eating
      behavior.

PMID- 19591887
TI  - In vitro activity of Tachyplesin III alone and in combination with terbinafine
      against clinical isolates of dermatophytes.
AB  - Aim of our study was to investigate the in vitro effects of Tachyplesin III (TP),
      a potent disulfide-linked peptide, in dermatophytes infections, with respect to
      or in combination with terbinafine (TERB), against 20 clinical isolates of
      dermatophytes belonging to four species. A broth microdilution method following
      the CLSI recommendations (M38-A) was used for testing drugs alone and in
      combination. TERB MICs were significantly lower than those observed for TP
      (p<0.001). Testing for antifungal agents in combination was performed for TERB
      with TP for all the 20 isolates. TERB activity in combination with TP showed
      indifferent activity for 14 of the 20 isolates (70%); synergic activity for 6 of
      the 20 isolates (30%); no antagonistic activity was observed. Further experiments
      were conducted with Microsporum canis 133, Trichophyton rubrum 62 and
      Trichophyton mentagrophytes 91 for fungal biomass. TP and TERB did not show a
      significant growth reduction compared to the control against T. mentagrophytes
      and T. rubrum. A significant difference of growth reduction both for TP and TERB
      compared to controls was observed for M. canis (p<0.01). In conclusion our study
      demonstrated that Tachyplesin III has potential activity against dermatophytes.
      In addition, we observed that the in vitro activity of Tachyplesin III can be
      enhanced upon combination with terbinafine. Synergy could permit lower doses of
      the individual antifungal agents to be used more effectively and/or safely.

PMID- 19591888
TI  - Molecular cloning, structural analysis and modelling of the AcAFP antifungal
      peptide from Aspergillus clavatus.
AB  - An abundantly secreted thermostable peptide (designed AcAFP) with a molecular
      mass of 5777 Da was isolated and purified in a previous work from a local strain
      of A. clavatus (VR1). Based on the N-terminal amino acid (aa) sequence of the
      AcAFP peptide, an oligonucleotide probe was derived and allowed the amplification
      of the encoding cDNA by RT-PCR. This cDNA fragment encodes a pre-pro-protein of
      94 aa which appears to be processed to a mature product of 51 aa cys-rich
      protein. The deduced aa sequence of the pre-pro-sequence reveals high similarity
      with ascomycetes antifungal peptide. Comparison of the nucleotide sequence of the
      genomic fragment and the cDNA clone revealed the presence of an open reading
      frame of 282 bp interrupted by two small introns of 89 and 56 bp with conserved
      splice site. The three-dimensional (3D) structure modeling of AcAFP exhibits a
      compact structure consisting of five anti-parallel beta barrel stabilized by four
      internal disulfide bridges. The folding pattern revealed also a cationic site and
      spatially adjacent hydrophobic stretch. The antifungal mechanism was investigated
      by transmission and confocal microscopy. AcAFP cause cell wall altering in a dose
      dependent manner against the phytopathogenic fungus Fusarium oxysporum.

PMID- 19591889
TI  - Stability to gastrointestinal enzymes and structure-activity relationship of beta
      casein-peptides with antihypertensive properties.
AB  - Physiological digestion plays a key role in the formation and degradation of
      angiotensin-converting enzyme (ACE)-inhibitory peptides. In this study, we
      evaluated the impact of a simulated gastrointestinal digestion on the stability
      of eight peptides previously identified in fermented milk with antihypertensive
      activity. Two of these identified peptides with sequences LHLPLP and
      LVYPFPGPIPNSLPQNIPP, possess ACE-inhibitory activity in vitro and
      antihypertensive activity in vivo. The results showed that LHLPLP was resistant
      to digestive enzymes. In contrast, LVYPFPGPIPNSLPQNIPP was totally hydrolyzed and
      its activity decreased after incubation with pepsin and a pancreatic extract. The
      peptide LHLPLP was incubated with ACE and was found to be a true inhibitor of the
      enzyme and to exhibit a competitive inhibitor pattern. A structure-activity
      relationship study of this peptide was carried out by synthesizing several
      modified peptides related to the sequence LHLPLP. The substitution of amino acid
      Leu in the penultimate position by Gly improved the ACE-inhibitory activity
      twofold and the substitution of Pro at C-terminal position by Arg increased the
      activity twofold, with an IC50 of LHLPLR as low as 1.8 microM.

PMID- 19591890
TI  - Using reduced amino acid composition to predict defensin family and subfamily:
      Integrating similarity measure and structural alphabet.
AB  - Defensins are essentially ancient natural antibiotics with potent activity
      extending from lower organisms to humans. They can inhibit the growth or
      virulence of micro-organisms directly or indirectly enhance the host's immune
      system. The successful prediction of defensin peptides will provide very useful
      information and insights for the basic research of defensins. In this study, by
      selecting the N-peptide composition of reduced amino acid alphabet (RAAA)
      obtained from structural alphabet named Protein Blocks as the feature parameters,
      the increment of diversity (ID) is firstly developed to predict defensins family
      and subfamily. The jackknife test based on 2-peptide composition of reduced amino
      acid alphabet (RAAA) with 13 reduced amino acids shows that the overall accuracy
      of prediction are 91.36% for defensin family, and 94.21% for defensin subfamily.
      The results indicate that ID_RAAA is a simple and efficient prediction method for
      defensin peptides.

PMID- 19591891
TI  - Codon number shapes peptide redundancy in the universal proteome composition.
AB  - The proteomes catalogued in the UniRef100 database were collected into a single
      proteome set and examined for actual versus theoretical pentapeptide occurrences.
      We found a highly diversified degree of pentapeptide redundancy. Numerically, 953
      pentamers are expressed only once in the protein world, whereas 103 pentamers
      occur more than 50,000 times. Moreover, it seems that 417 potentially possible
      pentapeptides are not present in the protein world. On the whole, tracing the
      redundancy profile of the protein world as a function of pentapeptide occurrences
      reveals a quasi-Gaussian curve, with tails representing scarcely and repeatedly
      occurring 5-mers. Analysis of physico-chemical-biological parameters shows that
      codon number is the main factor influencing and favoring specific pentapeptide
      frequencies in the universal proteome composition. That is, when compared to the
      set of never-expressed 5-mers, the pentapeptides frequently represented in the
      universal proteome are endowed with a higher number of multi-codonic amino acids.
      In contrast, the bulkiness degree and the hydrophobicity level play a smaller
      role. Unexpectedly, the heat of formation of pentapeptide appears to have the
      least influence.

PMID- 19591892
TI  - Evaluation of high-throughput genotoxicity assays used in profiling the US EPA
      ToxCast chemicals.
AB  - Three high-throughput screening (HTS) genotoxicity assays-GreenScreen HC GADD45a
      GFP (Gentronix Ltd.), CellCiphr p53 (Cellumen Inc.) and CellSensor p53RE-bla
      (Invitrogen Corp.)-were used to analyze the collection of 320 predominantly
      pesticide active compounds being tested in Phase I of US. Environmental
      Protection Agency's ToxCast research project. Between 9% and 12% of compounds
      were positive for genotoxicity in the assays. However, results of the varied
      tests only partially overlapped, suggesting a strategy of combining data from a
      battery of assays. The HTS results were compared to mutagenicity (Ames) and
      animal tumorigenicity data. Overall, the HTS assays demonstrated low sensitivity
      for rodent tumorigens, likely due to: screening at a low concentration, coverage
      of selected genotoxic mechanisms, lack of metabolic activation and difficulty
      detecting non-genotoxic carcinogens. Conversely, HTS results demonstrated high
      specificity, >88%. Overall concordance of the HTS assays with tumorigenicity data
      was low, around 50% for all tumorigens, but increased to 74-78% (vs. 60% for
      Ames) for those compounds producing tumors in rodents at multiple sites and,
      thus, more likely genotoxic carcinogens. The aim of the present study was to
      evaluate the utility of HTS assays to identify potential genotoxicity hazard in
      the larger context of the ToxCast project, to aid prioritization of
      environmentally relevant chemicals for further testing and assessment of
      carcinogenicity risk to humans.

PMID- 19591893
TI  - A case-control association study between the CYP3A4 and CYP3A5 genes and
      schizophrenia in the Chinese Han population.
AB  - In this study, variants of two genes coding for cytochrome P450 enzyme (CYP3A4
      and CYP3A5) were analysed in a case-control sample using 398 schizophrenic
      patients and 391 healthy controls. All subjects were unrelated Han Chinese from
      Shanghai. No difference was observed on the allelic or genotypic distribution of
      CYP3A4 and CYP3A5 gene polymorphisms between the groups. However, the two-marker
      haplotypes covering components CYP3A41G and CYP3A53 were observed to be
      significantly associated with schizophrenia (corrected global p=0.0009). In
      addition, we identified one common risk haplotype, G/G (present in 59.5% of the
      general population). The results suggest that CYP3A4 and CYP3A5 might play a role
      in genetic susceptibility to schizophrenia. However, confirmatory studies in
      independent samples are needed.

PMID- 19591894
TI  - Early loss of mitochondrial inner transmembrane potential in khat-induced cell
      death of primary normal human oral cells.
AB  - Previous studies suggest the use of khat, a psychostimulant plant used by
      millions of people in Middle East and Africa, as risk factor for oral cancer. We
      previously reported that khat is able to induce adverse affects, as cell cycle
      arrest and apoptosis, in normal human oral cells cultured in vitro. This study
      further investigates the more specific role played by mitochondria in khat
      induced cell death and the kinetics of the events involved in this process.
      Exposure of primary normal human oral keratinocytes and fibroblasts to khat
      extract resulted in a swift and sustained decrease of the mitochondrial inner
      transmembrane potential occurring within 0.5-1h. Loss of mitochondrial membrane
      potential preceded all other biochemical and morphologic changes, and was
      associated with a significant decrease in cell survival. Subsequently, apoptosis
      inducing factor was released from mitochondria into cytosol and relocated to
      nucleus. Cyclosporine A and bongkrekic acid delayed both the loss of
      mitochondrial inner transmembrane potential and the onset of cell death. This
      study describes a novel mechanism of khat-induced cell death in primary normal
      oral keratinocytes and fibroblasts involving an early pivotal effect on
      mitochondrial function and integrity.

PMID- 19591895
TI  - Species extinction and permanence of an impulsively controlled two-prey one
      predator system with seasonal effects.
AB  - Recently, the population dynamic systems with impulsive controls have been
      researched by many authors. However, most of them are reluctant to study the
      seasonal effects on prey. Thus, in this paper, an impulsively controlled two-prey
      one-predator system with the Beddington-DeAngelis type functional response and
      seasonal effects is investigated. By using the Floquet theory, the sufficient
      conditions for the existence of a globally asymptotically stable two-prey-free
      periodic solution are established. Further, it is proven that this system is
      permanent under some conditions via a comparison method involving multiple
      Lyapunov functions and meanwhile the conditions for extinction of one of the two
      prey and permanence of the remaining two species are given.

PMID- 19591896
TI  - The role of body centre of mass on haptic subjective vertical.
AB  - We examined to which extent proprioceptive information involved in the perception
      of subjective vertical corresponded to mechanical mass-based axes of the body.
      Blindfolded subjects (n=14) estimated their subjective vertical in conditions of
      deviation of the centre of mass (CM) of (1) the head-trunk unit or (2) the head
      segment alone. Verticality estimates (provided in a haptic modality) were
      significantly altered by the deviation of the head-trunk CM (by either 4 degrees
      or 7 degrees), indicating that the subjects used mass-based proprioceptive
      information stemming from the trunk. Modifying the perception of body orientation
      by shifting the trunk CM sideways while keeping the body vertical, deviates the
      subjective vertical towards the opposite side in a similar way to the so-called
      'E-effect'. The induced deviations of head CM (9.33 degrees) did not affect the
      subjective vertical, suggesting that when the balance of the body is not
      threatened, proprioceptive or vestibular information is prioritized to estimate
      gravitational direction.

PMID- 19591897
TI  - Continuously changed genes during postnatal periods in rat visual cortex.
AB  - The current study aimed to determine genes that changed continuously throughout
      the postnatal developmental process of the rat visual cortex. Tissue samples were
      taken at postnatal day 0, day 10 (before eye opening), day 20 (before the
      critical period) and day 45 (end of development) and subjected to microarray and
      real-time RT-PCR analyses. A temporal pattern of expression was revealed for 24
      genes that continuously increased (18 genes) or decreased (6 genes) as visual
      cortex development progressed and were common among all age groups. Our data
      provide a relevant set of genes whose expression levels correlate with visual
      cortex development and represent a novel group that may affect temporal-specific
      regulation.

PMID- 19591898
TI  - A randomized comparison of thalamic stimulation and lesion on self-paced finger
      movement in essential tremor.
AB  - Deep brain stimulation (DBS) and ablation (thalamotomy) of the motor thalamus
      reduce tremor and improve function of the contralateral hand in patients with
      essential tremor (ET). Neuroimaging and electrophysiological evidence suggest
      that unlike a focal lesion, high frequency stimulation affects widespread neural
      networks that include those involved in motor timing. The purpose of this pilot
      study was to compare the effects of thalamic stimulation and lesion on the timing
      of simple, self-paced finger movements in patients with ET. Twenty-one subjects
      with advanced ET were randomized to unilateral thalamotomy or DBS. Nine healthy
      controls were also enrolled. Index finger tapping was performed on both hands
      before and 6 months after surgery. Prior to surgery, timing of simple, repetitive
      index finger taps was abnormal in both TH and DBS subjects on the contralateral
      hand. After surgery, regularity was improved by both stimulation and thalamotomy
      with significantly more improvement in the TH group. On the ipsilateral (non
      targeted) hand, timing of index finger taps was improved by stimulation. These
      results suggest that temporal processing is differentially affected by
      stimulating and lesioning thalamocortical fibers. That timing regularity is
      improved ipsilateral to the stimulated thalamus provides evidence that DBS
      influences a widespread neural network involved in timing of simple repetitive
      movements.

PMID- 19591899
TI  - Neuroligand binding endophenotypes in blood cells distinguish two subsets of
      borderline personality disorder patients.
AB  - Neurotransmitter ligand binding in blood cells was assessed in borderline
      personality disorder (BDP) patients, testing the possibility that different
      biochemical endophenotypes might lie beneath a specific clinical presentation.
      The density of peripheral benzodiazepine receptors (PBR) and serotonin
      transporters were assessed in peripheral blood mononuclear cells (PBMC) and
      platelets, respectively, showing a decrease of both parameters. Moreover, a
      further significant decrease of PBR in PBMC was shown for those patients with a
      depressive trait. Further confirmation of the presence of different molecular
      endophenotypes underlying the dissimilar clinical presentations in BPD may
      advance our possibility of successfully treating these patients.

PMID- 19591901
TI  - Roles of nitric oxide in the homeostatic control of the excitation-inhibition
      balance in rat visual cortical networks.
AB  - The level of excitability of cortical neurons depends on the balance between
      their excitatory and inhibitory inputs (excitation/inhibition [E/I] balance). In
      the cortex, the E/I balance received by a neuron is dynamically maintained
      through a coordinated regulation of the strength of these inputs, described in
      term of homeostatic plasticity. Using a method allowing the determination of the
      E/I balance in rat cortical layer 5 pyramidal neurons (L5-PNs, the main output
      stage of the cortex), while keeping the interactions between excitatory and
      inhibitory networks functional, we examined the effects of high or low frequency
      of stimulation (HFS or LFS) protocols in layer 4 (in order to mimic thalamo
      cortical entries) on the E-I level of the neuronal network. We previously showed
      that the E/I balance of L5-PNs remains stable due to a dual potentiation or dual
      depression of E and I after HFS or LFS protocols. Here, using a specific neuronal
      nitric oxide synthase (nNOS) inhibitor, we show that the related potentiation or
      depression of E and I (underlying homeostatic plasticity processes) required nNOS
      activation. We also show that application of an unspecific blocker of nitric
      oxide synthase (NOS) or a nitric oxide (NO) scavenger induces an increase of the
      E/I balance suggesting a role for a tonic NO synthesis in the regulation of the
      network activity. It is concluded that, in the cortex, a phasic NO effect (due to
      activation of nNOS) is required for the induction of homeostatic plasticity
      processes whereas a tonic NO signal is involved in the regulation of a set-point
      value for the E/I balance.

PMID- 19591900
TI  - JNK1, a potential therapeutic target for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer death
      worldwide. Despite tremendous efforts to diagnose and institute new treatment
      regimens, the prognosis is still extremely poor. Therefore, knowledge of the
      molecular mechanisms governing the initiation, maintenance and progression of HCC
      is urgently needed. Recently, several groups have attributed an important role
      for c-Jun N-terminal kinase 1 (JNK1) in the pathogenesis of human HCC and its
      close association with the expression of HCC signature genes. In this review the
      various associations between JNK1 and HCC are discussed with the hope that
      targeting this pivotal kinase may lead to novel therapeutic approaches for this
      fatal disease.

PMID- 19591902
TI  - Extracellular magnesium enhances the damage to locomotor networks produced by
      metabolic perturbation mimicking spinal injury in the neonatal rat spinal cord in
      vitro.
AB  - An acute injury to brain or spinal cord produces profound metabolic perturbation
      that extends and exacerbates tissue damage. Recent clinical interventions to
      treat this condition with i.v. Mg(2+) to stabilize its extracellular
      concentration provided disappointing results. The present study used an in vitro
      spinal cord model from the neonatal rat to investigate the role of extracellular
      Mg(2+) in the lesion evoked by a pathological medium mimicking the metabolic
      perturbation (hypoxia, aglycemia, oxidative stress, and acid pH) occurring in
      vivo. Damage was measured by taking as outcome locomotor network activity for up
      to 24 h after the primary insult. Pathological medium in 1 mM Mg(2+) solution (1
      h) largely depressed spinal reflexes and suppressed fictive locomotion on the
      same and the following day. Conversely, pathological medium in either Mg(2+)-free
      or 5 mM Mg(2+) solution evoked temporary network depression and enabled fictive
      locomotion the day after. While global cell death was similar regardless of
      extracellular Mg(2+) solution, white matter was particularly affected. In ventral
      horn the number of surviving neurons was the highest in Mg(2+) free solution and
      the lowest in 1 mM Mg(2+), while motoneurons were unaffected. Although the
      excitotoxic damage elicited by kainate was insensitive to extracellular Mg(2+), 1
      mM Mg(2+) potentiated the effect of combining pathological medium with kainate at
      low concentrations. These results indicate that preserving Mg(2+) homeostasis
      rendered experimental spinal injury more severe. Furthermore, analyzing ventral
      horn neuron numbers in relation to fictive locomotion expression might provide a
      first estimate of the minimal size of the functional locomotor network.

PMID- 19591903
TI  - Role of neurosteroids in regulating cell death and proliferation in the late
      gestation fetal brain.
AB  - The neurosteroid allopregnanolone (AP) is a GABAergic agonist that suppresses
      central nervous system (CNS) activity in the adult brain, and by reducing
      excitotoxicity is considered to be neuroprotective. A role for neurosteroids in
      the developing brain, particularly in late gestation, is still debated. The aim
      of this study was to investigate effects on proliferation and cell death in the
      brain of late gestation fetal sheep after inhibition of AP synthesis using
      finasteride, a 5alpha-reductase type 2 (5alpha-R2) inhibitor. Catheters were
      implanted in fetal sheep at approximately 125 days of gestation. At 3-4 days
      postsurgery, fetuses received infusions of either finasteride (20 mg/kg/h; n=5),
      the AP analogue alfaxalone (5 mg/kg/h; n=5), or finasteride and alfaxalone
      together (n=5). Brains were obtained at 24 h after infusion to determine cell
      death (apoptotic or necrotic) and cell proliferation in the hippocampus and
      cerebellum, areas known to be susceptible to excitotoxic damage. Finasteride
      treatment significantly increased apoptosis (activated caspase-3 expression) in
      hippocampal CA3 and CA1, and cerebellar molecular and granular layers, an effect
      abolished by co-infusion of alfaxalone and finasteride. Double-label
      immunohistochemistry showed that both neurons and astrocytes were caspase-3
      positive. Finasteride treatment also increased the number of dead (pyknotic)
      cells in the hippocampus and cerebellum (Purkinje cells), but not when
      finasteride+alfaxalone was infused. Cell proliferation (Ki-67-immunoreactivity)
      increased after finasteride treatment; double-labeling showed the majority of Ki
      67-positive cells were astrocytes. Thus, steroids such as AP appear to influence
      the constitutive rate of apoptosis and proliferation in the hippocampus and
      cerebellum of the fetal brain, and suggest an important role for neurosteroids in
      the development of the brain.

PMID- 19591904
TI  - Thalidomide inhibition of vascular remodeling and inflammatory reactivity in the
      quinolinic acid-injected rat striatum.
AB  - Effects of thalidomide administration on vascular remodeling, gliosis and
      neuronal viability have been studied in excitotoxin-injected rat striatum.
      Intrastriatal injection of quinolinic acid (QUIN) caused time-dependent changes
      (durations of 6 h, 1 and 7 d post-injection) in vascular remodeling. QUIN
      excitotoxic insult was associated with increased numbers of vessels (laminin or
      collagen IV markers) demonstrating considerable abnormalities in morphology,
      including short fragments and vascular loops. Non-lesioned striatum, with
      injection of phosphate buffer solution (PBS) as a vehicle, showed no evidence for
      vascular remodeling. A maximal extent of vascular remodeling was measured at 1 d
      post-QUIN and was correlated with marked increases in microgliosis (ED1 marker)
      and astrogliosis (glial fibrillary acidic protein [GFAP] marker) relative to
      control PBS injection. Double staining of laminin with ED1 and GFAP demonstrated
      areas of close association of glial cells with blood vessels. Treatment of QUIN
      injected animals with the anti-inflammatory compound, thalidomide significantly
      inhibited vascular remodeling (by 43%) and reduced microgliosis (by 33%) but was
      ineffective in modifying extents of astrogliosis. Intrastriatal QUIN injection
      was associated with a marked loss of striatal neurons relative to non-lesioned
      control with thalidomide treatment exhibiting a significant degree of
      neuroprotection (24% recovery) against QUIN-induced neurotoxicity. These results
      suggest close links between microglial-mediated inflammatory responses and
      vascular remodeling, with inflammatory reactivity associated with, and
      contributing to, neuronal damage in excitotoxically-lesioned striatum.

PMID- 19591905
TI  - Paternal deprivation during infancy results in dendrite- and time-specific
      changes of dendritic development and spine formation in the orbitofrontal cortex
      of the biparental rodent Octodon degus.
AB  - The aim of this study in the biparental rodent Octodon degus was to assess the
      impact of paternal deprivation on neuronal and synaptic development in the
      orbitofrontal cortex, a prefrontal region which is essential for emotional and
      cognitive function. On the behavioral level the quantitative comparison of
      parental behaviors in biparental and single-mother families revealed that (i)
      degu fathers significantly participate in parental care and (ii) single-mothers
      do not increase their maternal care to compensate the lack of paternal care. On
      the brain structural level we show in three-week-old father-deprived animals that
      layer II/III pyramidal neurons in the orbitofrontal cortex displayed
      significantly lower spine densities on apical and basal dendrites. Whereas
      biparentally raised animals have reached adult spine density values at postnatal
      day 21, fatherless animals seem "to catch up" by a delayed increase of spine
      density until reaching similar values as biparentally raised animals in
      adulthood. However, in adulthood reduced apical spine numbers together with
      shorter apical dendrites were observed in father-deprived animals, which
      indicates that dendritic growth and synapse formation (seen in biparental animals
      between postnatal day 21 and adulthood) were significantly suppressed. These
      results demonstrate that paternal deprivation delays and partly suppresses the
      development of orbitofrontal circuits. The retarded dendritic and synaptic
      development of the apical dendrites of layer II/III pyramidal neurons in the
      orbitofrontal cortex of adult fatherless animals may reflect a reduced excitatory
      connectivity of this cortical subregion.

PMID- 19591906
TI  - Membrane current-based mechanisms for excitability transitions in neurons of the
      rat mesencephalic trigeminal nuclei.
AB  - Since Hodgkin's first description of three classes of excitability in crustacean
      nerve axons (1948), theoretical studies have used mathematical models to
      demonstrate that small changes in the parameters describing ionic currents could
      result in transitions between classes of membrane excitability. However, these
      transitions have rarely been investigated experimentally. Here, we show that
      states of excitability in rat mesencephalic V (Mes V) neurons can be classified
      into three groups, with manipulations of the 4-aminopyridine sensitive K(+)
      current (I(4-AP)) or persistent Na(+) current (I(NaP)) leading to the
      corresponding transitions. However, alterations in the hyperpolarization
      activated cation current (I(h)), tetraethylammonium (TEA)-sensitive K(+) current,
      or Cd(2+)-sensitive Ca(2+) current were ineffective in causing these transitions.
      These results provide experimental evidence for the excitability transitions
      predicted by Hodgkin and characterize their ionic mechanisms in Mes V neurons.

PMID- 19591907
TI  - BIS/BAS, cortical oscillations and coherence in response to emotional cues.
AB  - The present study explored the effect of the individual differences related to
      BIS and BAS (Behavioural Inhibition and Activation System) on brain oscillations,
      in response to appetitive and aversive emotional stimuli. EEG cortical measures
      (delta, theta, alpha, and gamma) were recorded, during viewing IAPS figures, that
      varied in terms of pleasantness and arousal. Withdrawal (BIS system) and
      appetitive (BAS system) behaviour showed opposite patterns of subjective
      responses. Also, a specific frontal network was found to be responsive to the
      relevance of emotional cues. Moreover an increased response for high arousing
      (negative and positive) stimuli in comparison with low arousing and neutral
      stimuli was found within the left and right frontal areas. Specifically delta and
      theta band have a significant role in monitoring the attentional significance of
      emotions. Finally, the effects of subjective evaluation and individual
      differences were discussed at light of the two-dimensional model of emotion
      processing, that is the valence and the arousing power of emotional cues.

PMID- 19591908
TI  - Spontaneous categorization of vocal imitations in African grey parrots (Psittacus
      erithacus).
AB  - The ability to categorize elements of the environment is a fundamental aspect of
      information processing. Many experiments demonstrate the ability of birds and non
      human primates to classify items according to their perceptual similarities. Few
      data are available regarding spontaneous classification of items according to a
      non-perceptual account in non-human animals. Here, we report unexpected results
      obtained with African grey parrots learning the referential use of French labels.
      Parrots did not learn the correct labels but they spontaneously produced more
      labels corresponding to food when a food item was presented to them and more
      labels corresponding to an object when shown an object item, although they were
      never rewarded for doing so. These results demonstrate a form of spontaneous
      categorization by using vocal imitation of the human language.

PMID- 19591909
TI  - Sound is involved in multimodal communication of Loxosceles intermedia Mello
      Leitao, 1934 (Araneae; Sicariidae).
AB  - Signals of different modalities are involved during courtship of the brown spider
      Loxosceles intermedia. A spine on the pedipalp is rubbed against the grooves on
      the retrolateral region of the chelicerae producing stridulatory signals, which
      have a dominant frequency of the airborne component range around 770 Hz for
      females and around 170 Hz for males. These values are significantly lower for the
      substrate-borne component. The sound pressure level of stridulatory signals lies
      below 50 dB and the velocity values below 1mm/s. The copulation frequency does
      not depend on the presence of pedipalps in females; however, in males the removal
      of pedipalps decreases the courtship frequency. During courtship, females vibrate
      their abdomens after being touched by the courting male, producing tremulatory
      signals with the dominant frequency below 100 Hz, sound pressure level below 60
      dB and velocity below 3mm/s. This vibration may function as a sign of the
      akinesia state since it precedes the introduction of the embolus. Cuticular
      compounds probably determine the recognition of the male by the female. Data from
      the present study corroborate the generalist nature of L. intermedia in which
      signals of different modalities are used during courtship.

PMID- 19591910
TI  - A preliminary study of the effects of handling type on horses' emotional
      reactivity and the human-horse relationship.
AB  - Handling is a crucial component of the human-horse relationship. Here, we report
      data from an experiment conducted to assess and compare the effect of two
      training methods. Two groups of six Welsh mares were trained during four sessions
      of 50 min, one handled with traditional exercises (halter leading,
      grooming/brushing, lifting feet, lunging and pseudo-saddling (using only girth
      and saddle pad) and the second group with natural horsemanship exercises
      (desensitization, yielding to body pressure, lunging and free-lunging). Emotional
      reactivity (ER) and the human-horse relationship (HHR) were assessed both prior
      to and following handling. A social isolation test, a neophobia test and a bridge
      test were used to assess ER. HHR was assessed through test of spontaneous
      approach to, and forced approach by, an unknown human. Horses' ER decreased after
      both types of handling as indicated by decreases in the occurrence of whinnying
      during stressful situations. Head movement (jerk/shake) was the most sensitive
      variable to handling type. In the spontaneous approach tests, horses in the
      traditional handling group showed higher latencies to approach a motionless
      person after handling than did the natural horsemanship group. Our study suggests
      that natural horsemanship exercises could be more efficient than traditional
      exercises for improving horses' HHR.

PMID- 19591912
TI  - Power-laws in the genomic distribution of coding segments in several organisms:
      an evolutionary trace of segmental duplications, possible paleopolyploidy and
      gene loss.
AB  - Large-scale features of the spatial arrangement of protein-coding segments (PCS)
      are investigated by means of the inter-PCS spacers' size distributions, which
      have been found to follow power-laws. Linearity in double-logarithmic scale
      extends to several orders of magnitude in the genomes of organisms as disparate
      as mammals, insects and plants. This feature is also present in the most compact
      eukaryotic genomes and in half of the examined bacteria, despite their very
      limited non-coding space. We have tried to determine the sequence of events in
      the course of genomes' evolution which may account for the formation of the
      observed size distributions. The proposed mechanism essentially includes two
      types of events: (i) segmental duplications (and possibly paleopolyploidy), and
      (ii) the subsequent loss of most of the duplicated genes. It is shown by computer
      simulations that the formulated scenario generates power-law-like inter-PCS
      spacers' size distributions, which remain robust for a variety of parameter
      choices, even if insertion of external sequences, such as viruses or
      proliferating retroelements is included. Moreover, power-laws are preserved after
      most of the non-coding DNA has been removed, thus explaining the finding of this
      pattern in genomes as compact as that of Takifugu rubripes.

PMID- 19591911
TI  - The "lunching" effect: pigeons track motion towards food more than motion away
      from it.
AB  - Four experiments measured pigeons' pecking at a small touch-screen image (the CS)
      that moved towards or away from a source of food (the US). The image's
      effectiveness as a CS was dependent on its motion, direction, and distance
      relative to the US. Pecking to the CS increased with proximity to the US when the
      CS moved towards the US (Experiment 1). This held true even when a departing CS
      signalled a US of greater magnitude (Experiment 2). Response rates to stationary
      stimuli were greater the closer they were to the hopper; but rate was less than
      when the same spot was part of a motion towards food, and greater than when it
      was part of a motion away (Experiment 3). The rate of responding in all three
      cases (motion towards, stationary, motion away) decreased exponentially with
      distance from the hopper. The distance and motion effects observed under these
      Pavlovian contingencies were different when pecking to the spot was required for
      reinforcement (Experiment 4).

PMID- 19591913
TI  - Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects
      on the GABAergic system.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Q'eqchi' Maya possess a large selection of
      plants to treat neurological disorders, including epilepsy and susto (fright), a
      culture-bound illness related to anxiety disorders. AIM OF THE STUDY: To
      investigate the activity of antiepileptic and anxiolytic plants in the GABAergic
      system, and determine if there is a pharmacological basis for plant selection.
      MATERIALS AND METHODS: Ethanol extracts of 34 plants were tested in vitro for
      their ability to inhibit GABA-transaminase (GABA-T) or bind to the GABA(A)
      benzodiazepine (BZD) receptor, two principal drug targets in epilepsy and
      anxiety. Pharmacological activity was correlated with relative frequency of use,
      based on informant consensus. RESULTS: Ten plants showed greater than 50% GABA-T
      inhibition at 1mg/ml, while 23 showed greater than 50% binding to the GABA(A)-BZD
      receptor at 250 microg/ml. Piperaceae, Adiantaceae and Acanthaceae families were
      highly represented and active in both assays. There was a significant positive
      correlation between GABA-T inhibition and relative frequency of use for epilepsy,
      and an even stronger correlation between GABA(A) binding and relative frequency
      of use for susto (fright). CONCLUSIONS: Clearly, Q'eqchi' traditional knowledge
      of antiepileptic and anxiolytic plants is associated with the use of
      pharmacologically active plants. Based on the evidence, it is suggested that the
      mechanism of action for some traditionally used plants may be mediated through
      the GABAergic system.

PMID- 19591915
TI  - Early kinetics of the transcriptional response of human leukocytes to
      staphylococcal superantigenic enterotoxins A and G.
AB  - The severity of Staphylococcus aureus sepsis is positively associated with
      staphylococcal enterotoxin A (SEA) and negatively associated with the enterotoxin
      gene cluster (egc), which encodes five staphylococcal enterotoxins (SE). It was
      recently demonstrated that SE can induce human leukocytes to release inflammatory
      mediators. Contrary to SEG (one of the five egc superantigens), SEA induces a
      strong proinflammatory/Th1 response, including tumor necrosis factor-alpha and
      macrophage inflammatory protein-1 alpha production. Here, we investigated the
      very early transcriptional response of human PBMC to these two SEs. We confirm
      that SEA is more potent than SEG. Importantly, our data also suggest that the
      early response to SE is likely induced more by T cells than by monocytes. In
      addition, negative feedback control is triggered at the same time as
      proinflammatory processes (inflammation and apoptosis). It confirms at the
      molecular level new models of sepsis pathophysiology as concomitant and opposite
      sides of a given mechanism participating to response to bacterial compound are
      both necessary. This preliminary study highlights the potential of
      transcriptional studies for unraveling the very early mechanisms of leukocyte
      responses to SE. Further studies are needed to understand the mechanisms
      underlying the putative synergy between SE and other bacterial components.

PMID- 19591916
TI  - ECVAM's ongoing activities in the area of acute oral toxicity.
AB  - The 7th Amendment of the Cosmetics Directive (2003/15/EC) set up timelines for
      banning animal testing and marketing of cosmetic products and their ingredients
      tested on animals. For most of the human health effects, including acute
      toxicity, the deadline for these bans was in March 2009. Moreover, the new
      Regulation EC 1907/2006 on Registration, Evaluation, Authorisation and
      Restriction of Chemicals (REACH) provided a strong impetus towards the
      application of alternative approaches to reduce the number of animals used for
      toxicological testing. Therefore, the European Centre for the Validation of
      Alternative Methods (ECVAM) is currently putting considerable effort into
      developing and validating alternative methods in the field of acute toxicity. The
      main activities in this area include: (1) the Integrated Project ACuteTox, funded
      by the European Commission's 6th Framework Programme in 2005 with the aim to
      develop and pre-validate a testing strategy to fully replace acute oral toxicity
      testing in vivo; (2) a follow-up validation study to assess the predictive
      capacity of the validated BALB/3T3 Neutral Red Uptake cytotoxicity assay to
      discriminate between toxic/hazardous (LD(50)<2,000 mg/kg) substances and
      substances not classified for acute toxicity (LD(50)>2,000 mg/kg); (3) an
      approach to identify compounds with LD(50)>2,000 mg/kg using information from 28
      days repeated dose toxicity studies.

PMID- 19591914
TI  - Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and
      behavior in adult offspring.
AB  - Methamphetamine is a commonly abused psychostimulant that causes addiction and is
      often abused by pregnant women. Acute or chronic administration of
      methamphetamine elevates the levels of the extracellular monoamine
      neurotransmitters, such as dopamine. The aim of the present study was to show
      whether prenatal exposure to methamphetamine (5mg/kg, entire gestation) or saline
      in Wistar rats induces changes in dopamine levels and its metabolites in the
      nucleus accumbens, and in behavior (locomotor activity, rearing, and immobility)
      after the administration of a challenge dose of methamphetamine (1mg/kg) or
      saline in male offspring. We found that adult offspring prenatally exposed to
      methamphetamine had higher basal levels of dopamine (about 288%),
      dihydroxyphenylacetic acid (about 67%) and homovanillic acid (about 74%) in
      nucleus accumbens. An increased basal level of dopamine corresponds to lower
      basal immobility in offspring prenatally exposed to methamphetamine. The acute
      injection of methamphetamine in adulthood increased the level of dopamine in the
      nucleus accumbens, which is related to an increase of locomotion and rearing
      (exploration). In addition, prenatally methamphetamine-exposed rats showed higher
      response to the challenge dose of methamphetamine, when compared to prenatally
      saline-exposed rats. In conclusion, rats exposed to methamphetamine in utero have
      shown changes in the mesolimbic dopaminergic system and were more sensitive to
      the administration of the acute dose of methamphetamine in adulthood.

PMID- 19591917
TI  - Cytotoxicity of carboxylic acid functionalized single wall carbon nanotubes on
      the human intestinal cell line Caco-2.
AB  - The unique properties of carbon nanotubes (CNTs) have been explored for their use
      in biomedical sciences and in biotechnological fields; however, their possible
      toxic effects are of concern. The sources of human exposure to nanomaterials
      include inhalation, ingestion, dermal contact and injection. The pulmonary and
      dermal effects of CNTs in vitro have been previously studied with contradictory
      results, but data on intestinal cells are scarce. The aim of this study was to
      evaluate the cytotoxicity of single wall CNTs functionalized with carboxylic acid
      on differentiated and non-differentiated Caco-2 cells, derived from a human
      intestinal adenocarcinoma. Biomarkers assessed were neutral red uptake (NR),
      protein content (PT), a tetrazolium salt (MTS) metabolization, LDH leakage (LDH)
      and cell viability by means of the trypan blue exclusion test (TBET). Moreover, a
      morphological study was performed. Cells were exposed to concentrations between 5
      and 1,000 microg/ml CNTs and toxic effects were studied after 24h of exposure. NR
      and MTS results showed a concentration-dependent trend with an inhibitory
      response from 100 microg/ml CNT, together with an increase in LDH leakage. TBET
      resulted in an 80% reduction at higher concentrations, and finally PT was only
      modified at higher concentrations. Overall, results indicated cytotoxic effects
      on the Caco-2 cells with differentiated cultures showing a higher sensitivity.
      Thus, a hazard assessment of CNTs is necessary as the nanotechnology industry
      grows, and more nanoscale wastes are released into the environment.

PMID- 19591918
TI  - A stable fish reporter cell line to study estrogen receptor transactivation by
      environmental (xeno)estrogens.
AB  - Cross-species differences between human and fish estrogen receptor (ER) binding
      by environmental chemicals have been reported. To study ER transactivation in a
      fish cellular context, we stably co-transfected the PLHC-1 fish hepatoma cell
      line with a rainbow trout estrogen receptor (rtER) and the luciferase reporter
      gene driven by an estrogen response element (ERE). This new cell model, called
      PELN-rtER (for PLHC-1-ERE-Luciferase-Neomycin), responded to 17beta-estradiol
      (E2) in a both concentration- and temperature-dependent manner, as well as to
      environmental ER ligands from different chemical classes: natural and synthetic
      estrogens, zearalenone metabolites, genistein, alkyphenoles and benzophenone
      derivatives. The comparison with other in vitro models, i.e. human reporter cell
      lines (HELN-rtER, MELN) and vitellogenin induction in primary cultures of rainbow
      trout hepatocytes, showed an overall higher sensitivity of the human cells for a
      majority of ligands, except for benzophenone derivatives which were active at
      similar or lower concentrations in fish cells, suggesting species-specificity for
      these substances. Correlation analyses suggest that the fish cell line is closer
      to the trout hepatocyte than to the human cell context, and could serve as a
      relevant mechanistic tool to study ER activation in fish hepatic cellular
      context.

PMID- 19591919
TI  - Localization of Type 1 Diabetes susceptibility in the ancestral haplotype 18.2 by
      high density SNP mapping.
AB  - Previous studies have suggested that the ancestral haplotype 18.2 (AH18.2)
      carries additional susceptibility gene to Type 1 Diabetes (T1D) on the Major
      Histocompatibility Complex (MHC). We analyzed 10 DR3/TNFa1b5 homozygous subjects
      in order to establish the conservation of the AH18.2 and then compared this
      conserved region with other DR3 haplotype, the AH8.1. The Illumina's HumanHap550
      Bead chip was used to perform an extensive genotyping of the MHC region. The
      AH18.2 was highly conserved between DDR1 and HLA-DQA1 genes; therefore most
      probably the second susceptibility gene is located within this region. We can
      exclude the region centromeric to HLA-DRA gene and telomeric to DDR1 gene. A
      comparison between the AH18.2 and AH8.1 haplotypes showed that 233 SNPs were
      different in the aforementioned conserved region. These data suggest that the
      1.65 Mb MHC region between DDR1 and HLA-DRA genes is likely to carry additional
      susceptibility alleles for T1D on the AH18.2 haplotype.

PMID- 19591921
TI  - Nitrated plasma albumin as a marker of nitrative stress and neonatal
      encephalopathy in perinatal asphyxia.
AB  - Reactive nitrogen species (RNS) have been shown to play a major role in the
      pathophysiology of hypoxic-ischemic cerebral injury. Using a novel sensitive
      ELISA allowing the quantification of nitrated albumin (nitroalbumin) in plasma,
      we tested the hypothesis that perinatal asphyxia increases nitrating RNS
      generation by verifying whether the concentration of one of its target proteins
      is correlated with the clinical outcome. We assayed nitroalbumin in 114 plasma
      samples collected during the first hour, at day 1, and at day 4 of life from 48
      term newborns suffering from perinatal asphyxia and correlated this marker with
      neurological and systemic neonatal outcomes. Nitroalbumin levels at day 1, but
      not at days 0 and 4, were significantly increased in patients who developed
      moderate or severe encephalopathy compared to those who had a normal neurological
      evolution or developed mild encephalopathy (median: 14.4 ng/ml versus 7.3 ng/ml,
      respectively). In contrast, nitroalbumin concentration at day 1 was not
      associated with systemic complications. First-hour and fourth-day nitroalbumin
      concentrations did not differ with respect to the neonatal neurological course.
      At day 0, nitroalbumin levels also correlated with circulating leukocytes. We
      conclude that plasma nitroalbumin seems to be a specific marker of neurological
      injury after perinatal asphyxia and may serve as a secondary end-point in
      neuroprotective clinical trials.

PMID- 19591920
TI  - Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium
      2-yl)porphyrin, MnTE-2-PyP(5+), via suppression of oxidative stress in a mouse
      model of breast tumor.
AB  - MnTE-2-PyP(5+) is a potent catalytic scavenger of reactive oxygen and nitrogen
      species, primarily superoxide and peroxynitrite. It therefore not only attenuates
      primary oxidative damage, but was found to modulate redox-based signaling
      pathways (HIF-1alpha, NF-kappaB, SP-1, and AP-1) and thus, in turn, secondary
      oxidative injury also. Cancer has been widely considered an oxidative stress
      condition. The goal of this study was to prove if and why a catalytic SOD
      mimic/peroxynitrite scavenger would exert anti-cancer effects, i.e., to evaluate
      whether the attenuation of the oxidative stress by MnTE-2-PyP(5+) could suppress
      tumor growth in a 4T1 mouse breast tumor model. Tumor cells were implanted into
      Balb/C mouse flanks. Three groups of mice (n=25) were studied: control (PBS) and
      2 and 15 mg/kg/day of MnTE-2-PyP(5+) given subcutaneously twice daily starting
      when the tumors averaged 200 mm(3) (until they reached approximately 5-fold the
      initial volume). Intratumoral hypoxia (pimonidazole, carbonic anhydrase), HIF
      1alpha, VEGF, proliferating capillary index (CD105), microvessel density (CD31),
      protein nitration, DNA oxidation (8-OHdG), NADPH oxidase (Nox-4), apoptosis
      (CD31), macrophage infiltration (CD68), and tumor drug levels were assessed. With
      2 mg/kg/day a trend toward tumor growth delay was observed, and a significant
      trend was observed with 15 mg/kg/day. The 7.5-fold increase in drug dose was
      accompanied by a similar (6-fold) increase in tumor drug levels. Oxidative stress
      was largely attenuated as observed through the decreased levels of DNA damage,
      protein 3-nitrotyrosine, macrophage infiltration, and NADPH oxidase. Further,
      hypoxia was significantly decreased as were the levels of HIF-1alpha and VEGF.
      Consequently, suppression of angiogenesis was observed; both the microvessel
      density and the endothelial cell proliferation were markedly decreased. Our study
      indicates for the first time that MnTE-2-PyP(5+) has anti-cancer activity in its
      own right. The anti-cancer activity via HIF/VEGF pathways probably arises from
      the impact of the drug on the oxidative stress. Therefore, the catalytic
      scavenging of ROS/RNS by antioxidants, which in turn suppresses cellular
      transcriptional activity, could be an appropriate strategy for anti-cancer
      therapy. Enhancement of the anti-cancer effects may be achieved by optimizing the
      dosing regime, utilizing more bioavailable Mn porphyrins (MnP), and combining MnP
      treatment with irradiation, hyperthermia, and chemotherapy. Mn porphyrins may be
      advantageous compared to other anti-cancer drugs, owing to their radioprotection
      of normal tissue and the ability to afford pain management in cancer patients via
      prevention of chronic morphine tolerance.

PMID- 19591922
TI  - Are antioxidants useful for treating skeletal muscle atrophy?
AB  - Changes in the skeletal muscle protein mass frequently occur in both
      physiological and pathological states. Muscle hypotrophy, in particular, is
      commonly observed during aging and is characteristic of several pathological
      conditions such as neurological diseases, cancer, diabetes, and sepsis. The
      skeletal muscle protein content depends on the relative rates of synthesis and
      degradation, which must be coordinately regulated to maintain the equilibrium.
      Pathological muscle depletion is characterized by a negative nitrogen balance,
      which results from disruption of this equilibrium due to reduced synthesis,
      increased breakdown, or both. The current view, mainly based on experimental
      data, considers hypercatabolism as the major cause of muscle protein depletion.
      Several signaling pathways that probably contribute to muscle atrophy have been
      identified, and there is increasing evidence that oxidative stress, due to
      reactive oxygen species production overwhelming the intracellular antioxidant
      systems, plays a role in causing muscle depletion both during aging and in
      chronic pathological states. In particular, oxidative stress has been proposed to
      enhance protein breakdown, directly or by interacting with other factors. This
      review focuses on the possibility of using antioxidant treatments to target
      molecular pathways involved in the pathogenesis of skeletal muscle wasting.

PMID- 19591923
TI  - The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is dependent
      on its association with the protein tyrosine phosphatase SHP-1.
AB  - 3'-Phosphoinositide-dependent protein kinase-1 (PDK1), the direct upstream kinase
      of Akt, can localize to the nucleus during specific signalling events. The
      mechanism used for its import into the nucleus, however, remains unresolved as it
      lacks a canonical nuclear localization signal (NLS). Expression of activated Src
      kinase in C6 glioblastoma cells promotes the association of tyrosylphosphorylated
      PDK1 with the NLS-containing tyrosine phosphatase SHP-1 as well as the nuclear
      localization of both proteins. A constitutive nucleo-cytoplasmic SHP-1:PDK1
      shuttling complex is supported by several lines of evidence including (i) the
      distribution of both proteins to similar subcellular compartments following
      manipulation of the nuclear pore complex, (ii) the nuclear retention of SHP-1
      upon overexpression of a PDK1 protein bearing a disrupted nuclear export signal
      (NES), and (iii) the exclusion of PDK1 from the nucleus upon overexpression of
      SHP-1 lacking the NLS or following siRNA-mediated knock-down of SHP-1. The latter
      case results in a perinuclear distribution of PDK1 that corresponds with the
      distribution of PIP3 (phosphatidylinositol 3,4,5-triphosphate), while a PDK1
      protein bearing a mutated PH domain that abrogates PIP3-binding is excluded from
      the nucleus. Our data suggest that the SHP-1:PDK1 complex is recruited to the
      nuclear membrane by binding to perinuclear PIP3, whereupon SHP-1 (and its NLS)
      facilitates active import. Export from the nucleus relies on PDK1 (and its NES).
      The intact complex contributes to Src kinase-induced, Akt-sensitive podial
      formation in C6 cells.

PMID- 19591926
TI  - Using the low-frequency Raman spectroscopy to analyze the crystallization of
      amorphous indomethacin.
AB  - This paper gives a detailed analysis of the low-frequency Raman spectrum (LFRS)
      in the 5-250cm(-1) region, corresponding to collective vibrations, in the
      crystalline forms and in the amorphous state of indomethacin (IMC). This study
      points out the high sensitivity of the LFRS to detect, identify and evaluate the
      first traces of crystallization in comparison with high-frequency regions where
      internal vibration bands are detected. This analysis reveals that amorphous IMC
      prepared by cryogrinding instantaneously partially crystallizes at room
      temperature in the stable gamma phase, well below T(g)=43 degrees C. A method
      based on the treatment of the LFRS to determine precise and very low volume of
      crystallized material within amorphous matrix is described and used to analyze
      the crystallization kinetics of ground amorphous IMC powder. This study
      demonstrates that Raman spectroscopy is also a well-adapted technique to point
      out small amount of amorphous state in crystalline matrix. Crystallization of
      ground IMC powder was also analyzed by isothermal microcalorimetry experiments,
      which is one of the most widely used methods to analyze isothermal
      crystallization and to evaluate crystallinity.

PMID- 19591924
TI  - Characterization of salivaricin CRL 1328, a two-peptide bacteriocin produced by
      Lactobacillus salivarius CRL 1328 isolated from the human vagina.
AB  - Salivaricin CRL 1328 is a heat-stable bacteriocin produced by Lactobacillus
      salivarius CRL 1328, a strain isolated from healthy human vagina, with potential
      applications for preventing urogenital infections. The objective of this study
      was to characterize the locus responsible for salivaricin CRL 1328 production and
      its mechanism of action against Enterococcus faecalis MP97 as the sensitive
      strain. Oligonucleotides were designed based on sequences of antimicrobial
      peptides previously described in the literature. The salivaricin CRL 1328 cluster
      was identified, sequenced and analyzed. This cluster was similar to the
      previously described ABP118 which codified for a two-peptide bacteriocin. The
      putative mature peptides of salivaricin CRL 1328, Salalpha and Salbeta were
      chemically synthesized. These peptides did not show bacteriocin activity when
      assayed individually. Both peptides exhibited optimal antimicrobial activity at
      an equimolar ratio. Spectroscopic fluorescence assays were carried out using the
      synthetic peptides to study the effect of salivaricin on proton motive force.
      This bacteriocin was shown to dissipate membrane potential and the transmembrane
      proton gradient, both components of proton motive force. E. faecalis MP97 cells
      treated with salivaricin CRL 1328 peptides were observed in transmission electron
      microscopy which revealed ultrastructural modifications of the cell wall.

PMID- 19591925
TI  - Impaired mitochondrial trafficking in Huntington's disease.
AB  - Impaired mitochondrial function has been well documented in Huntington's disease.
      Mutant huntingtin is found to affect mitochondria via various mechanisms
      including the dysregulation of gene transcription and impairment of mitochondrial
      function or trafficking. The lengthy and highly branched neuronal processes
      constitute complex neural networks in which there is a large demand for
      mitochondria-generated energy. Thus, the impaired mitochondrial trafficking in
      neuronal cells may play an important role in the selective neuropathology of
      Huntington's disease. Here we discuss the evidence for the effect of the
      Huntington's disease protein huntingtin on the intracellular trafficking of
      mitochondria and the involvement of this defective trafficking in the
      pathogenesis of Huntington's disease.

PMID- 19591927
TI  - Comparison of dissolution profiles obtained from nifedipine extended release once
      a day products using different dissolution test apparatuses.
AB  - In order to improve the predictability of dissolution testing new apparatuses
      have been proposed that mimic hydrodynamic and mechanical conditions in the
      gastrointestinal tract. In this study tested were four different nifedipine
      extended release (ER) formulations using the paddle apparatus and the
      reciprocating cylinder as pharmacopoeial test devices as well as two newly
      developed test apparatuses: the rotating beaker apparatus and the dissolution
      stress test apparatus. Investigated were Adalat OROS in strengths of 30 and 60
      mg, and two hydrophilic matrix formulations: 60 mg nifedipine Coral and Nifedipin
      Sandoz 40 mg retard. The results demonstrate that the dissolution characteristic
      of the ER tablets is strongly dependent on the applied test conditions. The
      dosage form related food effects for Coral 60 mg tablets that were previously
      observed in human bioequivalence studies could be predicted with the two non
      compendial dissolution test devices. The dissolution of Sandoz 40 mg tablets was
      very sensitive to all applied test conditions. The stable drug delivery
      characteristics of Adalat OROS observed in numerous in vivo studies was also
      observed in all of the dissolution tests. In conclusion, the present study shows
      that besides pH dependency the aspect of the mechanical robustness may be an
      essential factor affecting the dissolution characteristic of hydrogel matrix
      formulations.

PMID- 19591929
TI  - Lipid nanoparticles with different oil/fatty ester ratios as carriers of
      buprenorphine and its prodrugs for injection.
AB  - Buprenorphine is a promising drug for the treatment of chronic pain and opioid
      dependence. The aim of the present work was to evaluate the feasibility of lipid
      nanoparticles with different oil/fatty ester ratios for injection of
      buprenorphine. To improve the release properties and analgesic duration of the
      drug, ester prodrugs were also incorporated into the nanoparticles for
      evaluation. Linseed oil and cetyl palmitate were respectively chosen as the
      liquid lipid and solid lipid in the inner phase of the nanoparticulate systems.
      Differential scanning calorimetry (DSC) was performed, and the particle size,
      zeta potential, molecular environment, and lipid/water partitioning were
      determined to characterize the state of the drug/prodrug and lipid modification.
      The in vitro release kinetics were measured by a Franz assembly. DSC showed that
      systems without oil (solid lipid nanoparticles, SLNs) had a more ordered
      crystalline lattice in the inner matrix compared to those with oil
      (nanostructured lipid carriers, NLCs and lipid emulsion, LE). The mean diameter
      of the nanoparticles ranged between 180 and 200nm. The in vitro drug/prodrug
      release occurred in a delayed manner in decreasing order as follows: SLN>NLC>LE.
      It was found that the release rate was reduced following an increase in alkyl
      ester chains in the prodrugs. The in vivo antinociception was examined by a cold
      ethanol tail-flick test in rats. Compared to an aqueous solution, a prolonged
      analgesic duration was detected after an intravenous injection of buprenorphine
      loaded SLNs and buprenorphine propionate (Bu-C3)-loaded NLCs (with 10% linseed
      oil in the lipid phase). The Bu-C3 in NLCs even showed a maximum antinociceptive
      activity for 10h. In vitro erythrocyte hemolysis and lactate dehydrogenase (LDH)
      release from neutrophils demonstrated a negligible toxicity of these carriers.
      Our results indicate the feasibility of using lipid nanoparticles, especially
      SLNs and NLCs, as parenteral delivery systems for buprenorphine and its prodrugs.

PMID- 19591930
TI  - Interactions between rye (Secale cereale) root border cells (RBCs) and pathogenic
      and nonpathogenic rhizosphere strains of Fusarium culmorum.
AB  - Interactions of rye (Secale cereale) root border cells (RBCs), generated during
      plant growth and surrounding the root cap, with nonpathogenic rhizosphere
      Fusarium culmorum isolates: DEMFc2 (PGPF) and DEMFc5 (DRMO), and a pathogenic
      strain DEMFc37 were studied in test tube experiments. The effect of water
      suspended RBCs released from the rye root cap on the rate of macroconidia
      germination and hyphae (mycelial) growth of F. culmorum strains was also
      examined. It was found that root caps of 3-d-old rye seedlings (with the root
      length of 20mm) were surrounded with a layer of RBCs generated in a number
      specific for this plant species of 1980+/-30. Introduction of the macroconidia of
      the tested F. culmorum strains into the root zone of 3-d-old seedlings resulted,
      after 3d of incubation, in the formation of mantle-like structures only in the
      rhizosphere of plants inoculated with the pathogenic DEMFc37 strain. The
      macroconidia were suspended in (1) water, (2) a water mixture with root caps
      deprived of RBCs, (3) Martin medium, (4) malt extract broth, and (5) a water
      mixture with rye RBCs, and their percentage germination was determined during 96
      h incubation at 20 degrees C. Germination of the macroconidia of all the tested
      F. culmorum strains suspended in the rich growth media (Martin and malt extract
      broth) and in the mixture with RBCs was significantly speeded up. While only an
      average of 16.6 % of macroconidia suspended in water germinated after 96-h
      incubation, more than 90 % of those suspended in the growth media or in the
      mixture with RBCs germinated after 24h of incubation. In all the treatments, the
      highest rate of macroconidia germination was found in suspensions of the
      pathogenic strain and the lowest in macroconidial suspensions of the PGPF strain.
      The stimulatory effect of RBCs was not specific to the pathogenic strain.
      Nevertheless, microscopic observation revealed that it was only in the suspension
      containing a mixture of rye RBCs and macroconidia of the pathogenic strain that
      after 48-h incubation compact clusters of hyphae and RBCs, resembling mantle-like
      structures found in the root zone of plants inoculated only with the pathogenic
      strain but not inoculated with DRMO and PGPF strain, were formed.

PMID- 19591928
TI  - P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its
      prediction using an in combo PAMPA model.
AB  - The purpose of the study was to assess the permeability of mouse blood-brain
      barrier (BBB) to a diverse set of compounds in the absence of P-glycoprotein
      (Pgp) mediated efflux, to predict it using an in combo PAMPA model, and to
      explore its role in brain penetration classification (BPC). The initial brain
      uptake (K(in)) of 19 compounds in both wild-type and Pgp mutant [mdr1a(-/-)] CF-1
      mice was determined by the in situ brain perfusion technique. PAMPA measurements
      were performed, and the values were used to develop an in combo model, including
      Abraham descriptors. Published rodent K(in) values were used to enhance the
      dataset and validate the model. The model predicted 92% of the variance of the
      training set permeability. In all, 182 K(in) values were considered in this
      study, spanning four log orders of magnitude and where Pgp decreased brain uptake
      by as much as 14-fold. The calculated permeability-surface area (PS) values along
      with literature reported brain tissue binding were used to group molecules in
      terms of their brain penetration classification. The in situ BBB permeability can
      be predicted by the in combo PAMPA model to a satisfactory degree, and can be
      used as a lower-cost, high throughput first-pass screening method for BBB passive
      permeability.

PMID- 19591931
TI  - Tissue estradiol is selectively elevated in receptor positive breast cancers
      while tumour estrone is reduced independent of receptor status.
AB  - Previous studies have suggested elevated estrogen production in tumour-bearing
      breast quadrants as well as in breast cancers versus benign tissue. Using highly
      sensitive assays, we determined breast cancer tissue estrogen concentrations
      together with plasma and benign tissue estrogen concentrations in each quadrant
      obtained from mastectomy specimens (34 postmenopausal and 13 premenopausal
      women). We detected similar concentrations of each of the three major estrogens
      estradiol (E(2)), estrone (E(1)) and E(1)S in tumour-bearing versus non-tumour
      bearing quadrants. Considering malignant tumours, intratumour E(1) levels were
      reduced in cancer tissue obtained from pre- as well as postmenopausal women
      independent of tumour ER status (average ratio E(1) cancer: benign tissue of 0.2
      and 0.3, respectively; p<0.001 for both groups), suggesting intratumour
      aromatization to be of minor importance. The most striking finding was a
      significant (4.1-8.6-fold) increased E(2) concentration in ER positive tumours
      versus normal tissue (p<0.05 and <0.001 for pre- and postmenopausal patients,
      respectively), contrasting low E(2) concentrations in ER- tumours (p<0.01 and
      <0.001 comparing E(2) levels between ER+ and ER- tumours in pre- and
      postmenopausals, respectively). A possible explanation to our finding is
      increased ligand receptor binding capacity for E(2) in receptor positive tumours
      but alternative factors influencing intratumour estrogen disposition cannot be
      excluded.

PMID- 19591932
TI  - Effects of B cell depletion on T cell allogeneic immune responses: a strategy to
      reduce allogeneic sensitization.
AB  - BACKGROUND: B cell depletion has been employed to treat antibody-mediated organ
      transplantation rejection, although the effects on cellular immune responses have
      not been extensively investigated. METHODS: A model of B cell depletion used
      SCID/beige mice reconstituted with BALB/c splenocytes either depleted of B cells
      (BD) or not (BN). BD and B/N mice received C57BL/6 skin grafts and were
      sacrificed after 6 weeks (BD-S6 and BN-S6). RESULTS: Recall proliferative
      responses of BD-S6 splenocytes to C57BL/6 were significantly reduced compared to
      BN-S6, and central memory T cells' proportions (CD4(+)CD44(+)CD62L(+) or
      CD8(+)CD44(+)CD62L(+)) were significantly decreased in BD-S6 spleens. Recall IFN
      gamma production by BD-S6 splenocytes was significantly reduced compared to BN-S6
      splenocytes (p=0.0028). Survival times of C57BL/6 heart grafts were significantly
      longer in SCID/beige mice reconstituted with BD-S6 splenocytes (8.5+/-1.1 days)
      than for SCID/beige reconstituted with BN-S6 splenocytes (6.0+/-1.1 days;
      p=0.0006). Under cyclosporine therapy, C57BL/6 heart survival was significantly
      longer for SCID/beige reconstituted with BD-S6 splenocytes (17.5+/-6.4 days) than
      those reconstituted with BN-S6 splenocytes (6.2+/-1.5 days; p<0.0001).
      CONCLUSION: B cell depletion during allogeneic sensitization decreased memory T
      cells and recalls IFN-gamma production and reduced second-set allograft
      rejection.

PMID- 19591933
TI  - UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of
      p27.
AB  - The UBE3A/E6-AP is known to function both as an E3 ubiquitin ligase of the
      ubiquitin proteasome system and as a transcriptional coactivator. E6-AP shows
      brain-specific imprinting and loss of function of maternally inherited E6-AP
      causes Angelman syndrome. However, how the loss of function of E6-AP causes
      disease pathogenesis is poorly understood. Here, we show that E6-AP interacts
      with and promotes proteasome-mediated degradation of cyclin-dependent kinase
      inhibitor p27. E6-AP also directly ubiquitinates p27 in an in vitro
      ubiquitination assay. Partial knockdown of E6-AP increases the level of p27
      leading to cell cycle arrest. Interestingly, partial knockdown also increases the
      transcription of p27. Finally, we have demonstrated the increased levels of p27
      in E6-AP-maternal-deficient and null mice brain. Our result suggests that E6-AP
      not only enhances the degradation but also regulates the expression of p27 and
      its loss of function in Angelman syndrome might cause cell cycle alteration
      leading to disease pathogenesis.

PMID- 19591935
TI  - Altered responses of dopamine D3 receptor null mice to excitotoxic or anxiogenic
      stimuli: Possible involvement of the endocannabinoid and endovanilloid systems.
AB  - Dopamine and the endocannabinoids, anandamide and 2-arachidonoylglycerol,
      interact at several levels in the brain, with the involvement of both cannabinoid
      CB(1) receptors and transient receptor potential vanilloid type-1 (TRPV1)
      channels (which are alternative anandamide receptors). Using pharmacological,
      immunohistochemical and analytical approaches, we investigated the response of
      dopamine D(3) receptor null (D3R((-/-))) mice in models of epilepsy and anxiety,
      in relation to their brain endocannabinoid and endovanilloid tone. Compared to
      wild-type mice, D3R((-/-)) mice exhibited a delayed onset of clonic seizures,
      enhanced survival time, reduced mortality rate and more sensitivity to
      anticonvulsant effects of diazepam after intraperitoneal administration of
      picrotoxin (7 mg/kg), and a less anxious-like behaviour in the elevated plus maze
      test. D3R((-/-)) mice also exhibited different endocannabinoid and TRPV1, but not
      CB(1), levels in the hippocampus, nucleus accumbens, amygdala and striatum. Given
      the role played by CB(1) and TRPV1 in neuroprotection and anxiety, and based on
      data obtained here with pharmacological tools, we suggest that the alterations of
      endocannabinoid and endovanilloid tone found in D3R((-/-)) mice might account for
      part of their altered responses to excitotoxic and anxiogenic stimuli.

PMID- 19591934
TI  - Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC
      treatment of stroke.
AB  - We investigated the additive therapeutic effect of the combination treatment of
      stroke with sub-therapeutic doses of Simvastatin, a HMG-CoA reductase inhibitor,
      and bone marrow stromal cells (BMSCs). Rats were administered Simvastatin (0.5
      mg/kg), BMSCs (1x10(6)) or combination of Simvastatin and BMSCs starting at 24 h
      after stroke. Combination treatment significantly improved neurological outcome,
      enhanced angiogenesis and arteriogenesis, and increased the number of engrafted
      BMSCs in the ischemic brain. The number of engrafted-BMSCs and arteriogenesis was
      significantly correlated with functional outcome. Simvastatin significantly
      increased stromal cell-derived factor-1 (SDF1) expression in the ischemic brain
      and chemokine (CXC motif) receptor-4 (CXCR4) in BMSCs, and increased BMSC
      migration to RBMECs and astrocytes. Combination treatment of stroke upregulates
      the SDF1/CXCR4 axis and enhances BMSC migration into the ischemic brain,
      amplifies arteriogenesis and angiogenesis, and improves functional outcome after
      stroke.

PMID- 19591937
TI  - Exercise attenuates the clinical, synaptic and dendritic abnormalities of
      experimental autoimmune encephalomyelitis.
AB  - Voluntary exercise is beneficial in models of primarily neurodegenerative
      disorders. Whether exercise also affects inflammatory neurodegeneration is
      unknown. In the present study, we evaluated the clinical, synaptic and
      neuropathological effects of voluntary wheel running in mice with myelin
      oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE), a model of multiple sclerosis. Exercising EAE mice
      exhibited less severe neurological deficits compared to control EAE animals. The
      sensitivity of striatal GABA synapses to the stimulation of cannabinoid CB1
      receptors was dramatically downregulated following EAE induction, and was rescued
      by exercise in EAE mice with access to a running wheel. Finally, we found that
      exercise was able to contrast dendritic spine loss induced by EAE in striatal
      neurons, although the degree of inflammatory response was similar in the two
      experimental groups. Our work suggests that life style and experiences can impact
      the clinical course of inflammatory neurodegenerative diseases by affecting their
      synaptic bases.

PMID- 19591936
TI  - Murine Glut-1 transporter haploinsufficiency: postnatal deceleration of brain
      weight and reactive astrocytosis.
AB  - Glucose transporter type 1 (Glut-1) facilitates glucose flux across the blood
      brain-barrier. In humans, Glut-1 deficiency causes acquired microcephaly,
      seizures and ataxia, which are recapitulated in our Glut-1 haploinsufficient
      mouse model. Postnatal brain weight deceleration and development of reactive
      astrogliosis were significant by P21 in Glut-1(+/-) mice. The brain weight
      differences remained constant after P21 whereas the reactive astrocytosis
      continued to increase and peaked at P90. Brain immunoblots showed increased
      phospho-mTOR and decreased phospho-GSK3-beta by P14. After fasting, the mature
      Glut-1(+/-) females showed a trend towards elevated phospho-GSK3-beta, a possible
      neuroprotective response. Lithium chloride treatment of human skin fibroblasts
      from control and Glut-1 DS patients produced a 45% increase in glucose uptake.
      Brain imaging of mature Glut-1(+/-) mice revealed a significantly decreased
      hippocampal volume. These subtle immunochemical changes reflect chronic nutrient
      deficiency during brain development and represent the experimental correlates to
      the human neurological phenotype associated with Glut-1 DS.

PMID- 19591938
TI  - A genetic variation in the ADORA2A gene modifies age at onset in Huntington's
      disease.
AB  - Based on the pathophysiological role of adenosine A(2A) receptors in HD, we have
      evaluated the association of the 1976C/T single-nucleotide polymorphism in the
      ADORA2A gene (rs5751876) with residual age at onset (AAO) in HD. The study
      population consisted of 791 unrelated patients belonging to the Huntington French
      Speaking Network. The variability in AAO attributable to the CAG repeats number
      was calculated by linear regression using the log (AAO) as the dependent
      variable, and the respective rs5751876 genotypes as independent variables. We
      show that the rs5751876 variant significantly influences the variability in AAO.
      The R(2) statistic rose slightly but significantly (p=0.019) when rs5751876 T/T
      genotype was added to the regression model. Patients harbouring T/T genotype have
      an earlier AAO of 3.8 years as compared to C/C genotype (p=0.02). Our data thus
      strengthens the pathophysiological role of A(2A) receptors in Huntington's
      disease.

PMID- 19591940
TI  - Studying chaperone-proteases using a real-time approach based on FRET.
AB  - Chaperone-proteases are responsible for the processive breakdown of proteins in
      eukaryotic, archaeal and bacterial cells. They are composed of a cylinder-shaped
      protease lined on the interior with proteolytic sites and of ATPase rings that
      bind to the apical sides of the protease to control substrate entry. We present a
      real-time FRET-based method for probing the reaction cycle of chaperone
      proteases, which consists of substrate unfolding, translocation into the protease
      and degradation. Using this system we show that the two alternative bacterial
      ClpAP and ClpXP complexes share the same mechanism: after initial tag
      recognition, fast unfolding of substrate occurs coinciding with threading through
      the chaperone. Subsequent slow substrate translocation into the protease chamber
      leads to formation of a transient compact substrate intermediate presumably close
      to the chaperone-protease interface. Our data for ClpX and ClpA support the
      mechanical unfolding mode of action proposed for these chaperones. The general
      applicability of the designed FRET system is demonstrated here using in addition
      an archaeal PAN-proteasome complex as model for the more complex eukaryotic
      proteasome.

PMID- 19591939
TI  - Y-27632 improves rotarod performance and reduces huntingtin levels in R6/2 mice.
AB  - Huntington disease (HD) is a devastating, untreatable, dominantly inherited
      neurodegenerative disease. It is caused by an expanded CAG codon repeat that
      leads to an elongated polyglutamine tract in the N-terminus of the huntingtin
      (Htt) protein. Few mechanism-based therapeutic leads have been developed. Y
      27632, an inhibitor of the Rho-associated kinase ROCK, reduces Htt aggregation in
      cultured cells and Htt-induced neurodegeneration in Drosophila, but its effect in
      mice is unknown. We determined that Y-27632 is bioavailable in brain, with a half
      life of 60-90 min. We then initiated a trial in R6/2 mice, which express Htt exon
      1, administering 100 mg/kg/day of Y-27632 in drinking water. We did not observe a
      significant effect on brain weight, inclusion number or size, striatal medium
      spiny neuron number, clasping behavior, or lifespan. However, Y-27632 treatment
      improved rotarod performance significantly, and also reduced soluble brain Htt
      levels. The ROCK signaling pathway thus remains a promising therapeutic target
      for HD, and more potent inhibitors may prove useful.

PMID- 19591941
TI  - Crystal structure of Bacillus thuringiensis Cry8Ea1: An insecticidal toxin toxic
      to underground pests, the larvae of Holotrichia parallela.
AB  - Crystal (Cry) proteins belong to an insect toxin family encoded and expressed by
      a variety of Bacillus thuringiensis isolates, and are named due to their in vivo
      auto-crystallization abilities. To kill the infected host insects, protease
      activated Cry toxins should firstly be recognized by certain membrane receptors
      on the surface of insect midgut epithelial cells and consequently assemble
      together as lethal transmembrane pores. Here we report the 2.2-A crystal
      structure of Cry8Ea1 toxin, a Cry family member specifically toxic to the
      underground larvae of Holotrichia parallela. Superimposition of the domain I from
      Cry8Ea1 and other structurally characterized Cry toxins reveals an identical
      surface proline residue and a highly conserved kink of a helix, both of which
      have drawn comparatively little attention from previous researchers. Further
      structural analysis and functional studies suggest that both the proline and the
      helix kink might be essential in exposing a helix-helix hairpin, which is
      believed to be the very first step in the well-known "umbrella" model of the
      membrane penetration. In summary, we propose a plausible model of the initiation
      of Cry toxin domain I disassembly before membrane penetration and pore formation.

PMID- 19591942
TI  - An immune responsive complement factor D/adipsin and kallikrein-like serine
      protease (PoDAK) from the olive flounder Paralichthys olivaceus.
AB  - The cDNA encoding of a complement factor D/adipsin and kallikrein-like serine
      protease, designated PoDAK, was isolated from the olive flounder Paralichthys
      olivaceus. PoDAK cDNA encodes a polypeptide with 277 amino acids containing
      conserved catalytic triad residues of serine proteases. The amino acid sequence
      of PoDAK showed high similarity to the kallikrein-like protein of medaka,
      mammalian adipsin/complement factor D and tissue kallikrein homolog, KT-14 of
      trout, complement factor D of zebrafish, and shared 31.6-36.8% homology with
      complement factor D/adipsin known from other species, including mammals.
      Phylogenetic analysis revealed that PoDAK clustered with the kallikrein-like
      protein of medaka and mammalian adipsin/complement factor D and tissue kallikrein
      homolog KT-14 of trout. The expression of PoDAK mRNA was high in the gills and
      heart, moderate in muscle, liver, intestine, stomach, kidney, and spleen of
      healthy flounder, and increased in the kidney, liver, and spleen of flounder
      challenged by the viral hemorrhagic septicemia virus (VHSV) or Streptococcus
      iniae. In situ hybridization confirmed that PoDAK mRNA is localized in the kidney
      and heart of individuals infected with VHSV. Further investigations are needed to
      clarify the function of PoDAK in vivo and in vitro.

PMID- 19591943
TI  - Stress-related hormones modulate cytokine expression in the head kidney of
      gilthead seabream (Sparus aurata).
AB  - Neuro-endocrine and immune systems closely interact in fish, and their regulation
      is crucial for the maintenance of good health of cultured fish. We have used the
      seabream head kidney to study whether stress-related hormones can modulate the
      immune response. For this purpose, the effects of adrenaline, adrenocorticotropic
      hormone (ACTH) and cortisol on the expression of pro-inflammatory cytokines (TNF
      alpha, IL-1beta, IL-6) and the anti-inflammatory cytokine TGF-beta1 were
      determined by means of quantitative real-time PCR on isolated head kidney cells.
      ACTH (150 ng mL(-1)) caused an acute increase of TNF-alpha and IL-6 mRNA levels
      as well as an inhibition of IL-1beta expression. The expression of the anti
      inflammatory cytokine TGF-beta1 was also increased, although in a lower extent.
      Adrenaline (1 muM) early effects were only clear inhibiting IL-1beta expression
      but not TNF-alpha, IL-6 or TGF-beta1 mRNA levels, while a longer exposure to the
      hormone inhibited all cytokines. Moreover, cortisol (50 and 100 ng mL(-1))
      reduced the expression of all cytokines in a dose-dependent manner. Bacterial
      lipopolysaccharide (LPS) stimulated IL-1beta expression and inhibited that of the
      anti-inflammatory TGF-beta1, although it was ineffective on TNF-alpha and IL-6.
      In addition, adrenaline and cortisol decreased the LPS-stimulated IL-1beta
      expression, further demonstrating their previously reported anti-inflammatory
      effects. The combination of ACTH and LPS, on the other hand, did not affect LPS
      stimulated IL-1beta expression but was effective increasing TNF-alpha expression.
      Taking all these results in consideration, we conclude that the expression of pro
      and anti-inflammatory cytokines in the seabream head kidney is highly influenced
      by stress-related hormones, thus indicating an important role for the endocrine
      system in the modulation of the immune response in teleost fish.

PMID- 19591944
TI  - Rodlet cells in the thymus of the zebrafish Danio rerio (Hamilton, 1822).
AB  - The conspicuous rodlet cell (RC) of teleost fishes is a remarkable but still
      poorly understood phenomenon in the biology of this group. Since their discovery
      by Thelohan in 1892, a confusing discussion about their nature and physiological
      function has ensued with various interpretations of RCs as protozoan parasites,
      gland cells, or a specific type of immune cell. Here we present a study on RCs in
      the zebrafish Danio rerio (Hamilton, 1822) and the first observation of their
      occurrence in the thymus, based on light- and electron-microscopy. RCs were
      confirmed in thymus-surrounding connective tissue, the thymic epithelium and the
      parenchyma. Very few (late) immature stages of RCs could be identified, already
      displaying some rodlets and a developing fibrillar cell border but often also
      signs of a degenerating Golgi apparatus. Apoptotic RCs occurred mostly below the
      surface epithelium. The mature RCs ejected their rodlets not only at the surface
      of the epithelium but also into the extracellular environment of the thymic
      parenchyma. Coalescence of the rodlets into "multi-core" units seems to represent
      an organ-specific feature. No cellular immune reaction of reticulum cells or
      granulocytes against RCs and their cellular products was observed. RCs in tight
      contact with lymphocytes showed conspicuous formation of dense structures in the
      capsule-like cell membrane, but dense membrane appositions were also observed
      between RCs and erythrocytes in blood vessels. The possibility of immigration and
      defective development of RCs in the thymus is discussed.

PMID- 19591945
TI  - EEG signatures of auditory activity correlate with simultaneously recorded fMRI
      responses in humans.
AB  - We recorded auditory-evoked potentials (AEPs) during simultaneous, continuous
      fMRI and identified trial-to-trial correlations between the amplitude of
      electrophysiological responses, characterised in the time domain and the time
      frequency domain, and the hemodynamic BOLD response. Cortical AEPs were recorded
      from 30 EEG channels within the 3 T MRI scanner with and without the collection
      of simultaneous BOLD fMRI. Focussing on the Cz (vertex) EEG response, single
      trial AEP responses were measured from time-domain waveforms. Furthermore, a
      novel method was used to characterise the single-trial AEP response within three
      regions of interest in the time-frequency domain (TF-ROIs). The latency and
      amplitude values of the N1 and P2 AEP peaks during fMRI scanning were not
      significantly different from the Control session (p>0.16). BOLD fMRI responses to
      the auditory stimulation were observed in bilateral secondary auditory cortices
      as well as in the right precentral and postcentral gyri, anterior cingulate
      cortex (ACC) and supplementary motor cortex (SMC). Significant single-trial
      correlations were observed with a voxel-wise analysis, between (1) the magnitude
      of the EEG TF-ROI1 (70-800 ms post-stimulus, 1-5 Hz) and the BOLD response in
      right primary (Heschl's gyrus) and secondary (STG, planum temporale) auditory
      cortex; and (2) the amplitude of the P2 peak and the BOLD response in left pre-
      and postcentral gyri, the ACC and SMC. No correlation was observed with single
      trial N1 amplitude on a voxel-wise basis. An fMRI-ROI analysis of functionally
      identified auditory responsive regions identified further single-trial
      correlations of BOLD and EEG responses. The TF amplitudes in TF-ROI1 and TF-ROI2
      (20-400 ms post-stimulus, 5-15 Hz) were significantly correlated with the BOLD
      response in all bilateral auditory areas investigated (planum temporale, superior
      temporal gyrus and Heschl's gyrus). However the N1 and P2 peak amplitudes,
      occurring at similar latencies did not show a correlation in these regions. N1
      and P2 peak amplitude did correlate with the BOLD response in bilateral
      precentral and postcentral gyri and the SMC. Additionally P2 and TF-ROI1 both
      correlated with the ACC. TF-ROI3 (400-900 ms post-stimulus, 4-10 Hz) correlations
      were only observed in the ACC and SMC. Across the group, the subject-mean N1 peak
      amplitude correlated with the BOLD response amplitude in the primary and
      secondary auditory cortices bilaterally, as well as the right precentral gyrus
      and SMC. We confirm that auditory-evoked EEG responses can be recorded during
      continuous and simultaneous fMRI. We have presented further evidence of an
      empirical single-trial coupling between the EEG and BOLD fMRI responses, and show
      that a time-frequency decomposition of EEG signals can yield additional BOLD fMRI
      correlates, predominantly in auditory cortices, beyond those found using the
      evoked response amplitude alone.

PMID- 19591946
TI  - In vivo MRI of endogenous stem/progenitor cell migration from subventricular zone
      in normal and injured developing brains.
AB  - Understanding the alterations of migratory activities of the endogenous neural
      stem/progenitor cells (NSPs) in injured developing brains is becoming
      increasingly imperative for curative reasons. In this study, 10-day-old neonatal
      rats with and without hypoxic-ischemic (HI) insult at postnatal day 7 were
      injected intraventricularly with micron-sized iron oxide particles (MPIOs),
      followed by serial high-resolution MRI at 7 T for 2 weeks. MRI findings were
      correlated to the histological analysis using iron staining and several
      immunohistochemical double staining. The results indicated that in normal and HI
      injured brains the NSPs from the subventricular zone (SVZ) were labeled by MPIOs,
      and migrated as newly created cells (iron+/BrdU+), neuroblasts (iron+/nestin+),
      astrocytes or astrocytes-like progenitor cells (iron+/GFAP+), and mature neurons
      (iron+/NeuN+). In normal brains, the endogenous NSPs mainly exhibited a
      tangential pattern in both rostral and caudal directions. The NSP radial
      migratory pattern could be observed in some rats. In the HI-injured brains during
      the same developmental period, the NSPs mainly migrated towards the HI lesion
      sites. The tangential, rostrocaudal migrations could be observed but impaired.
      These findings suggest that the NSP migratory pathways in SVZ change in response
      to the HI insult, likely due to the self-repairing efforts known in the neonatal
      brains. The MRI approach demonstrated here is potentially applicable to the in
      vivo and longitudinal study of NSP cell activities in developing brains under
      normal and pathological conditions and in therapeutic interventions.

PMID- 19591947
TI  - Hierarchical coding of characters in the ventral and dorsal visual streams of
      Chinese language processing.
AB  - Functional and spatial hierarchical organization of increasingly language-like
      word forms has been proposed for alphabetic languages at the occipitotemporal
      cortex for visual word recognition. In the logographic Chinese language system,
      similar functional and spatial hierarchical presentations of brain responses to
      sublexical orthographic structure are beginning to be explored. In this study, we
      used whole-brain fMRI to show that a hierarchical coding of increasingly language
      like character type is present in multiple Chinese language processing areas.
      Fluent Chinese readers were presented with Chinese synonyms/non-synonym pairs,
      identical/non-identical non-pronounceable pseudo-character pairs constructed with
      Chinese radicals, and identical/non-identical Korean character pairs. We observed
      the presence of a spatial gradient for increasing language-like character types
      in the ventral and dorsal visual streams of the cortex. At the left
      occipitotemporal cortex of the ventral visual stream, we observed a posterior-to
      anterior gradient of character type selectivity with the anterior fusiform region
      being more selective for real Chinese characters and the posterior fusiform
      region being more selective for Korean characters. At the left and right
      intraparietal sulci of the dorsal visual stream, a medial-to-lateral gradient of
      character type selectivity was observed, with the lateral edge being more
      selective for real Chinese characters, the medial edge being more selective for
      pseudo-characters, and with less activation attributable to Korean characters.
      Spatial gradients of selecting character type were also identified in prefrontal
      cortex, dorsal striatum and lateral temporal cortex. The results suggest that the
      left occipitotemporal cortex and both left and right intraparietal sulci are
      tuned with a functional and spatial hierarchical sensitivity to the presence of
      semantic elements as well as different orthographic structures.

PMID- 19591949
TI  - Right frontal cortex generates reward-related theta-band oscillatory activity.
AB  - When participants in a gambling game are given feedback as to whether they won or
      lost the previous bet, a series of stereotypical brain electrical responses can
      be observed in the electroencephalogram (EEG) and the stimulus-locked Event
      Related Potential (ERP). These include the Feedback-Related Mediofrontal
      Negativity (FRN), a posterior P300, and a feedback-induced increase in power at
      the theta (4 to 8 Hz) band over frontal scalp. Although the generators of the FRN
      and P300 have been studied previously, little is known about the generator of
      feedback-induced theta. We employed a gambling game in which participants chose
      either high-risk/high-reward or low-risk/low-reward bets to investigate these
      feedback-related responses. The FRN was not modulated by the riskiness of the
      bet, but both P300 and feedback-induced theta were of greater amplitude following
      high- relative to low-risk bets. Using a bilateral multi-source Beamformer
      approach, we localized the induced theta-band responses following wins and losses
      to partially overlapping regions in the right medial frontal cortex, possibly
      including the Anterior Cingulate. Using a dipole-fitting approach, we found that
      the generators of feedback-induced theta are anatomically distinct from those of
      the FRN and P300.

PMID- 19591948
TI  - Strategies for the generation of parametric images of [11C]PIB with plasma input
      functions considering discriminations and reproducibility.
AB  - Pittsburgh compound B or [11C]PIB is an amyloid imaging agent which shows a clear
      differentiation between subjects with Alzheimer's disease (AD) and controls.
      However the observed signal difference in other forms of dementia such as
      dementia with Lewy bodies (DLB) is smaller, and mild cognitively impaired (MCI)
      subjects and some healthy elderly normals may show intermediate levels of
      [11C]PIB binding. The cerebellum, a commonly used reference region for non
      specific tracer uptake in [11C]PIB studies in AD may not be valid in Prion
      disorders or monogenic forms of AD. The aim of this work was to: 1-compare
      methods for generating parametric maps of [11C]PIB retention in tissue using a
      plasma input function in respect of their ability to discriminate between AD
      subjects and controls and 2-estimate the test-retest reproducibility in AD
      subjects. 12 AD subjects (5 of which underwent a repeat scan within 6 weeks) and
      10 control subjects had 90 minute [11C]PIB dynamic PET scans, and arterial plasma
      input functions were measured. Parametric maps were generated with graphical
      analysis of reversible binding (Logan plot), irreversible binding (Patlak plot),
      and spectral analysis. Between group differentiation was calculated using
      Student's t-test and comparisons between different methods were made using p
      values. Reproducibility was assessed by intraclass correlation coefficients
      (ICC). We found that the 75 min value of the impulse response function showed the
      best group differentiation and had a higher ICC than volume of distribution maps
      generated from Logan and spectral analysis. Patlak analysis of [11C]PIB binding
      was the least reproducible.

PMID- 19591951
TI  - Phylogenetic relationships of four endemic genera of the Phasianidae in China
      based on mitochondrial DNA control-region genes.
AB  - The taxonomic status of some genera within the Phasianidae remains controversial.
      To demonstrate the phylogenetic relationships of four endemic genera
      (Tetraophasis, Ithaginis, Crossoptilon and Chrysolophus) and other 11 genera of
      Phasianidae in China, a total of 1070 nucleotides of mitochondrial DNA (mtDNA)
      control-region genes were sequenced. There are 376 variable sites including 345
      parsimony sites. The genetic distance ranged from 0.067 (Chrysolophus and
      Phasianus) to 0.181 (Perdix and Bambusicola) among the 15 genera. Maximum
      likelihood method was used to construct a phylogenetic tree, which grouped all
      the genera into two deeply divergent clades. Perdix was shown to be a non
      partridge genus. Alternatively, it appears ancestral to either partridges or
      pheasants. The sibling taxa of the four endemic genera were Lophophorus,
      Tragopan, Lophura and Phasianus, respectively. Calibrated rates of molecular
      evolution suggested that the divergence time between the four genera and related
      taxa was 4.00-5.00 million years ago, corresponding to the Pliocene. Considering
      their molecular phylogenetics, fossil and geographical distribution patterns, the
      four endemic genera might have originated in the southwestern mountains in China.

PMID- 19591950
TI  - A beta-scintillator for surface measurements of radiotracer kinetics in the
      intact rodent cortex.
AB  - Beta+-sensitive probes are useful tools for the measurement of radiotracer
      kinetics in small animals. They allow the cost-effective development of new PET
      tracers and offer the possibility to investigate a variety of cerebral processes.
      The study's main aim was the in vivo evaluation of a probe system for cerebral
      surface acquisitions. The detector system is a 0.2-mm thick scintillating disk of
      3-mm diameter, positioned close to the cerebral surface. The study consists of 4
      subparts: (1) simulation of the detection volume, (2) direct comparison with the
      classic intracortical beta probe regarding its capability to acquire kinetic
      data, (3) test of the ability to detect local tracer accumulations during
      infraorbital nerve (ION) electrostimulation and (4) demonstration of the
      feasibility to measure tracer kinetics in awake animals. Kinetic data acquired
      with 18F-fluorodeoxyglucose and 15O-H2O were fitted with standard compartment
      models. The surface probe measurements were in good agreement with those obtained
      using the intracortical scintillator. ION electrostimulation induced a marked
      increase in tracer accumulation adequately detected by the surface probe. In the
      head-fixed animal, a marked change in FDG kinetics was detected between the awake
      and anesthetized state. The novel surface probe system proved to be a valuable
      instrument for in vivo radiotracer studies of the cerebral cortex. Its main
      advantage is the absence of any tissue damage. In addition, serial acquisitions
      of tracer kinetics in the awake animal turned out to be feasible.

PMID- 19591952
TI  - Early meiosis in Rhynchospora pubera L. (Cyperaceae) is marked by uncommon
      ultrastructural features.
AB  - The family Cyperaceae has an unusual microsporogenesis in which tetrad formation
      does not occur. In addition, other cytological features are important, such as
      the occurrence of holokinetic chromosomes and post-reductional meiosis. We have
      examined the ultrastructural features of the pollen mother cell (PMC) of
      Rhynchospora pubera. Anthers of several sizes were analyzed using light and
      transmission electron microscopy. The PMC before meiosis presented a central
      nucleus and a regular profile of the nuclear envelope. During prophase I, the
      nucleus was in the abaxial region of the cell. This cellular polarization was
      accompanied by other marked ultrastructural features in the nuclear envelope.
      Morphological changes involved dilations of perinuclear cisterns and polarization
      of the nuclear pore complexes. The results show that polarization occurs in the
      initial phases of microsporogenesis in R. pubera, unlike other plant species.

PMID- 19591953
TI  - A one-trial inhibitory avoidance task to zebrafish: rapid acquisition of an NMDA
      dependent long-term memory.
AB  - The behavioral tasks aiming to evaluate learning and memory mechanisms currently
      available to zebrafish (Danio rerio) involve long training sessions frequently
      along multiple days and are based on shuttle box or active-avoidance protocols,
      preventing a detailed analysis of cellular and molecular time-dependent processes
      involved in memory acquisition and consolidation. In order to explore zebrafish's
      potential contribution to the characterization of the molecular machinery
      underlying learning and memory rapidly acquired and reliable paradigms are
      necessary. In this study we present a rapid and effective learning protocol in a
      single-trial inhibitory avoidance in zebrafish. In a simple apparatus, adult
      animals learned to refrain from swimming from a white into a dark compartment in
      order to avoid an electric shock during a single-trial training session that
      lasted less than 2 min. The resulting memory is robust, long-lasting and
      sensitive to NMDA-receptor antagonist MK-801 given in the tank water immediately
      after training. Experiments aiming to further characterize the events underlying
      memory formation, retrieval or extinction or those looking for cognitive
      profiling of mutants, neurotoxicological studies and disease models may benefit
      from this task, and together with complementary strategies available for
      zebrafish may significantly improve our current knowledge on learning and memory
      mechanisms.

PMID- 19591955
TI  - The PCM-basal body/primary cilium coalition.
AB  - The centrosome is an organelle that acts as a microtubule-organizing center
      (MTOC) throughout the cell cycle. Within the centrosome are often two components
      that each have an ability to organize microtubule structures: the centriole that
      has the potential to function as a basal body and nucleate a cilium or a
      flagellum and a mass of protein material that in the presence of a centriole is
      commonly referred to as the pericentriolar material (PCM) that organizes
      cytoplasmic and spindle microtubule arrays. One characteristic of a large variety
      of cells is the ability to express a non-motile primary cilium. It is now
      appreciated that the function of the primary cilium is integral to a variety of
      essential cell functions and defects affecting this structure underlie a variety
      of human disease. While the function of the primary cilium and manner in which a
      basal body organizes a primary cilium has received extensive attention there is
      now a need to explore the inter-relationship between the PCM and the basal
      body/primary cilium. It is this latter topic that is the focus of this review
      where we show that the PCM is integrated with the centriole to form a coalition
      that is essential for both the expression and function of the primary cilium as
      well as the organization and function of the cellular environment that surrounds
      it.

PMID- 19591954
TI  - Diagnostic trends in Clostridium difficile detection in Finnish microbiology
      laboratories.
AB  - Due to increased interest directed to Clostridium difficile-associated
      infections, a questionnaire survey of laboratory diagnostics of toxin-producing
      C. difficile was conducted in Finland in June 2006. Different aspects pertaining
      to C. difficile diagnosis, such as requests and criteria used for testing,
      methods used for its detection, yearly changes in diagnostics since 1996, and the
      total number of investigations positive for C. difficile in 2005, were asked in
      the questionnaire, which was sent to 32 clinical microbiology laboratories,
      including all hospital-affiliated and the relevant private clinical microbiology
      laboratories in Finland. The situation was updated by phone and email
      correspondence in September 2008. In June 2006, 28 (88%) laboratories responded
      to the questionnaire survey; 24 of them reported routinely testing requested
      stool specimens for C. difficile. Main laboratory methods included toxin
      detection (21/24; 88%) and/or anaerobic culture (19/24; 79%). In June 2006, 18
      (86%) of the 21 laboratories detecting toxins directly from feces, from the
      isolate, or both used methods for both toxin A (TcdA) and B (TcdB), whereas only
      one laboratory did so in 1996. By September 2008, all of the 23 laboratories
      performing diagnostics for C. difficile used methods for both TcdA and TcdB. In
      2006, the number of specimens processed per 100,000 population varied remarkably
      between different hospital districts. In conclusion, culturing C. difficile is
      common and there has been a favorable shift in toxin detection practice in
      Finnish clinical microbiology laboratories. However, the variability in
      diagnostic activity reported in 2006 creates a challenge for national monitoring
      of the epidemiology of C. difficile and related diseases.

PMID- 19591956
TI  - Differential transcriptome profiles of attenuated and hypervirulent strains of
      Mycobacterium bovis.
AB  - The identification of factors involved in the interaction of Mycobacterium bovis
      with the hosts will lead to new strategies to control bovine tuberculosis. In
      this study we compared the transcriptional profile of an attenuated M. bovis
      strain and a virulent M. bovis strain as a means to elucidate the molecular basis
      for their differential phenotype. Microarray and RT-qPCR results demonstrated
      that the expression of mce4D, Mb2607/Mb2608 and Mb3706c were up-regulated in the
      virulent strain whereas alkB, Mb3277c and Mb1077c were expressed at higher levels
      in the attenuated strain. These differential expression profiles were confirmed
      for Mb2607/Mb2608, mce4D, Mb1077c, alkB and Mb3277c during the replication of
      bacteria inside macrophages.

PMID- 19591957
TI  - Degradation of RIG-I following cytomegalovirus infection is independent of
      apoptosis.
AB  - Many viruses have evolved strategies to either evade or hijack host cell immune
      programs, as a means of promoting their own reproduction. For example, the human
      cytomegalovirus (HCMV) immediate-early protein vMIA/UL37ex1 inhibits host cell
      apoptosis, and its expression during infection aids virus replication. Here it is
      shown that stable expression of vMIA/UL37ex1 reduces cleavage of the innate
      immune response-proteins MAVS and RIG-I by caspases during apoptosis.
      Unexpectedly, it is demonstrated that RIG-I, but not MAVS, is degraded during
      HCMV infection. This process occurs in a non-apoptotic manner, and provides new
      evidence that HCMV may have evolved a unique strategy to evade RIG-I-mediated
      immune responses.

PMID- 19591959
TI  - NAD(P)H: Quinone oxidoreductase 1, glutathione S-transferase M1, environmental
      tobacco smoke exposure, and childhood asthma.
AB  - Environmental tobacco smoke (ETS) exposure might increase the risk for childhood
      asthma, and we hypothesized the effect may be modified by the phase II genes
      NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) M1.
      To investigate the genetic and environmental associations with asthma, GSTM1 and
      NQO1 functional polymorphisms and ETS were analyzed in a two-staged cross
      sectional study among elementary schoolchildren in Taiwan. Multiple logistic
      regression analysis revealed a significant association between the Ser allele of
      the NQO1 Pro187Ser polymorphism and asthma (OR=1.6, 95% CI 1.3-1.8). Although
      GSTM1 genotype itself was not significantly associated with asthma (OR=1.0, 95%
      CI 0.8-1.1), the GSTM1 genotype modified the association between the NQO1
      polymorphism and asthma in children exposed to ETS (p=0.0002). The NQO1 gene
      might be involved in the development of asthma, especially in children carrying
      the GSTM1 null genotype who are exposed to ETS.

PMID- 19591960
TI  - In vivo induction of the autophagic machinery in human bone marrow cells during
      Leishmania donovani complex infection.
AB  - Autophagy is a homeostatic process promoting cell survival in periods of stress.
      The induction of the autophagic machinery has also been implicated in both innate
      and adaptive immunity. Leishmania donovani, which is the causative pathogen of
      visceral leishmaniasis, is an intracellular parasite that invades and multiplies
      in bone marrow macrophages. We describe the induction of host cell autophagic
      machinery during acute natural bone marrow infection by L. donovani complex,
      detected by LC3B immunoblot. The successful treatment with liposomal amphotericin
      B resulted in the resolution of this phenomenon. Even though the role of
      autophagy in parasite biology has been previously studied, our findings show for
      the first time the in vivo host cell LC3B conversion as a marker of the induction
      of the autophagic machinery during infection with Leishmania parasite in real
      time conditions.

PMID- 19591958
TI  - gammaH2AX: A potential DNA damage response biomarker for assessing toxicological
      risk of tobacco products.
AB  - Differentiation among American cigarettes relies primarily on the use of
      proprietary tobacco blends, menthol, tobacco substitutes, paper porosity, paper
      additives, and filter ventilation. These characteristics substantially alter per
      cigarette yields of tar and nicotine in standardized protocols promulgated by
      government agencies. However, due to compensatory alterations in smoking behavior
      to sustain a preferred nicotine dose (e.g., by increasing puff frequency,
      inhaling more deeply, smoking more cigarettes per day, or blocking filter
      ventilation holes), smokers actually inhale similar amounts of tar and nicotine
      regardless of any cigarette variable, supporting epidemiological evidence that
      all brands have comparable disease risk. Consequently, it would be advantageous
      to develop assays that realistically compare cigarette smoke (CS)-induced
      genotoxicity regardless of differences in cigarette construction or smoking
      behavior. One significant indicator of potentially carcinogenic DNA damage is
      double strand breaks (DSBs), which can be monitored by measuring Ser 139
      phosphorylation on histone H2AX. Previously we showed that phosphorylation of
      H2AX (defined as gammaH2AX) in exposed lung cells is proportional to CS dose.
      Thus, we proposed that gammaH2AX may be a viable biomarker for evaluating
      genotoxic risk of cigarettes in relation to actual nicotine/tar delivery. Here we
      tested this hypothesis by measuring gammaH2AX levels in A549 human lung cells
      exposed to CS from a range of commercial cigarettes using various smoking
      regimens. Results show that gammaH2AX induction, a critical event of the
      mammalian DNA damage response, provides an assessment of CS-induced DNA damage
      independent of smoking topography or cigarette type. We conclude that gammaH2AX
      induction shows promise as a genotoxic bioassay offering specific advantages over
      the traditional assays for the evaluation of conventional and nonconventional
      tobacco products.

PMID- 19591962
TI  - Interval based fuzzy systems for identification of important genes from
      microarray gene expression data: Application to carcinogenic development.
AB  - In the present article, we develop two interval based fuzzy systems for
      identification of some possible genes mediating the carcinogenic development in
      various tissues. The methodology involves dimensionality reduction, classifying
      the genes through incorporation of the notion of linguistic fuzzy sets low,
      medium and high, and finally selection of some possible genes mediating a
      particular disease, obtained by a rule generation/grouping technique. The
      effectiveness of the proposed methodology, is demonstrated using five microarray
      gene expression datasets dealing with human lung, colon, sarcoma, breast cancer
      and leukemia. Moreover, the superior capability of the methodology in selecting
      important genes, over five other existing gene selection methods, viz.,
      Significance Analysis of Microarrays (SAM), Signal-to-Noise Ratio (SNR),
      Neighborhood analysis (NA), Bayesian Regularization (BR) and Data-adaptive (DA)
      is demonstrated, in terms of the enrichment of each GO category of the important
      genes based on P-values. The results are appropriately validated by earlier
      investigations, gene expression profiles and t-test. The proposed methodology has
      been able to select genes that are more biologically significant in mediating the
      development of a disease than those obtained by the others.

PMID- 19591961
TI  - Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred
      from 28S rDNA sequences.
AB  - The 28S rDNA from nine species of the genus Syphacia collected in Japan was
      sequenced, and the phylogenetic relationship was inferred from multiple sequence
      alignment of 28S rDNA by the MAFFT program. Phylogenetic tree indicates that S.
      petrusewiczi, which was the only species belonging to the subgenus Seuratoxyuris,
      has diverged earlier than other rodent pinworms examined and was distantly
      separated from the others genetically. It was revealed that S. agraria and S.
      vandenbrueli, whose subgeneric status has not been specified, belonged to the
      subgenus Syphacia together with other 6 species. Syphacia montana from
      Clethrionomys, Eothenomys and Microtus was very closely related to S. obvelata
      from Mus, and that S. frederici from Apodemus and S. vandenbrueli from Micromys
      were comparatively closely related to the former two species. The phylogenetic
      relationship among the three species of Syphacia found in Japanese Apodemus was
      inconsistent with the biogeography of host rodents. The co-evolutionary
      relationship between pinworm species and their host rodents may not be so strict
      and host switching has probably occurred frequently during the course of
      evolution.

PMID- 19591963
TI  - DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and
      related protozoan parasites.
AB  - Eukaryotic cell viability highly relies on genome stability and DNA integrity
      maintenance. The cellular response to DNA damage mainly consists of six
      biological conserved pathways known as homologous recombination repair (HRR), non
      homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR),
      nucleotide excision repair (NER), and methyltransferase repair that operate in a
      concerted way to minimize genetic information loss due to a DNA lesion.
      Particularly, protozoan parasites survival depends on DNA repair mechanisms that
      constantly supervise chromosomes to correct damaged nucleotides generated by
      cytotoxic agents, host immune pressure or cellular processes. Here we reviewed
      the current knowledge about DNA repair mechanisms in the most relevant human
      protozoan pathogens. Additionally, we described the recent advances to understand
      DNA repair mechanisms in Entamoeba histolytica with special emphasis in the use
      of genomic approaches based on bioinformatic analysis of parasite genome sequence
      and microarrays technology.

PMID- 19591964
TI  - Life science careers: how to make best use of Europe's brains.
AB  - Between February 11th and 13th 2009, the Young European Biotech Network invited
      thirty young life scientists to Frankfurt. During the first Conference on
      European Life Sciences Careers, they interacted with stakeholders from academia,
      industry and the European Commission to propose actions they deemed necessary to
      turn Europe into a more attractive work area for life scientists.

PMID- 19591965
TI  - Glucocorticoids, osteocytes, and skeletal fragility: the role of bone
      vascularity.
AB  - Glucocorticoid administration is required for many inflammatory and autoimmune
      diseases, but use of these drugs is associated with skeletal side effects
      including bone loss, fractures, and osteonecrosis. Fractures often occur without
      a reduction in bone mineral density, strongly suggesting that glucocorticoid
      excess adversely affects other aspects of bone strength. Although the primary
      effects of glucocorticoid excess on the skeleton are directly on bone cells, a
      vascular connection between these cells and the loss of bone strength appears
      likely. This review examines this connection and how it may explain the greater
      decline in bone strength than loss of bone mass that occurs with glucocorticoid
      excess.

PMID- 19591966
TI  - The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its
      mediation of the skeletal effects of low-density lipoprotein receptor-related
      protein 5 (LRP5).
AB  - Novel molecular pathways obligatory for bone health are being rapidly identified.
      One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT)
      mediation of the complete skeletal effects of low-density lipoprotein receptor
      related protein 5 (LRP5). Mounting evidence supports 5-HT as an important
      regulatory compound in bone with previous evidence demonstrating that bone cells
      possess functional pathways for responding to 5-HT. In addition, there is growing
      evidence that potentiation of 5-HT signaling via inhibition of the 5-HT
      transporter (5-HTT) has significant skeletal effects. The later is clinically
      significant as the 5-HTT is a popular target of pharmaceutical agents, such as
      selective serotonin reuptake inhibitors (SSRIs), used for the management of major
      depressive disorder and other affective conditions. The observation that 5-HT
      mediates the complete skeletal effects of LRP5 represents a significant paradigm
      shift from the traditional view that LRP5 located on the cell surface membrane of
      osteoblasts exerts direct skeletal effects via Wnt/beta-catenin signaling. This
      paper discusses the mounting evidence for skeletal effects of 5-HT and the
      ability of gut-derived 5-HT to satisfactorily explain the skeletal effects of
      LRP5.

PMID- 19591967
TI  - Macrophage migration inhibitory factor inhibits osteoclastogenesis.
AB  - MIF is an important regulator of innate and adaptive immunity, which is produced
      by a variety of cell types including activated T cells and macrophages. We
      examined the effects of MIF on osteoclastogenesis in bone marrow (BM) cultures
      from WT and MIF-deficient (KO) mice as well as the bone mass of MIF KO mice.
      Exogenous MIF inhibited osteoclast formation in BM cultures by decreasing fusion
      in cells that were treated with M-CSF and RANKL. However, inhibition of OCL
      formation by MIF treatment was not mediated by fusion-related molecules in
      heterogeneous bone marrow cultures. BM cultures from MIF KO mice that were
      treated with M-CSF and RANKL, PTH or vitamin D had significantly increased OCL
      number compared to cells from WT mice. MIF also significantly inhibited OCL
      formation in cultures of RAW 264.7 cells that were treated with RANKL. In
      addition, the number of CFU-GM and Mac-1(+) cells in the BM of MIF KO mice was
      greater than in WT controls. Trabecular bone volume (TBV) in the femurs and
      vertebrae of MIF KO mice was decreased compared to WT mice. In addition, serum
      bone resorption and formation markers were decreased in MIF KO mice compared to
      WT mice. These results demonstrate that MIF has inhibitory effects on OCL
      formation in vitro. We also found that BM cell cultures from MIF KO mice had an
      increased capacity to form osteoclasts. Furthermore, MIF KO animals had
      significantly decreased TBV with low turnover. We conclude that MIF is an
      inhibitor of osteoclastogenesis in vitro, which may regulate bone turnover via
      indirect mechanism in vivo.

PMID- 19591968
TI  - Moving and memorizing: motor planning modulates the recency effect in serial and
      free recall.
AB  - Motor planning has generally been studied in situations where participants carry
      out physical actions without a particular purpose. Yet in everyday life physical
      actions are usually carried out for higher-order goals. We asked whether two
      previously discovered motor planning phenomena--the end-state comfort effect and
      motor hysteresis--would hold up if the actions were carried out in the service of
      higher-order goals. The higher-order goal we chose to study was memorization. By
      focusing on memorization, we asked not only how and whether motor planning is
      affected by the need to memorize, but also how memory performance might depend on
      the cognitive demands of motor planning. We asked university-student participants
      to retrieve cups from a column of drawers and memorize as many letters as
      possible from the inside of the cups. The drawers were opened either in a random
      order (Experiment 1) or in a regular order (Experiments 2 and 3). The end-state
      comfort effect and motor hysteresis were replicated in these conditions,
      indicating that the effects hold up when physical actions are carried out for the
      sake of a higher-order goal. Surprisingly, one of the most reliable effects in
      memory research was eliminated, namely, the tendency of recent items to be
      recalled better than earlier items--the recency effect. This outcome was not an
      artifact of memory being uniformly poor, because the tendency of initial items to
      be recalled better than later items--the primacy effect--was obtained.
      Elimination of the recency effect was not due to the requirement that
      participants recall items in their correct order, for the recency effect was also
      eliminated when the items could be recalled in any order (Experiment 3). These
      and other aspects of the results support recent claims for tighter links between
      perceptual-motor control and intellectual (symbolic) processing than have been
      assumed in the past.

PMID- 19591969
TI  - The effects of humor on memory for non-sensical pictures.
AB  - Two experiments investigated the effects of humor on memory for non-sensical
      pictures. Each picture was given three labels that differed in the degree of
      humor: high, low, and no humor labels. In Experiment 1, the humor of the picture
      labels was manipulated between participants. Participants were shown 30 pictures
      for 10s each and were asked to rate the degree of humor of each picture. After
      the rating task, participants were asked to draw the pictures in an unexpected
      memory test. Performance in the memory test was best in the high humor label
      group, followed by the low and the no humor label groups. In Experiment 2,
      intention to learn (incidental versus intentional encoding tasks) as well as
      humor label was manipulated between the participants. In the incidental learning
      condition, the high humor group performed better than the low humor group, but in
      the intentional learning condition, there was no humor effect. The effects of
      humor on picture memory were discussed in terms of appraisal processing within a
      distinctiveness framework.

PMID- 19591970
TI  - A comparative study of laparoscopic extraperitoneal lymphadenectomy [correction
      of laparoscopy] with the use of ultrasonically activated shears.
AB  - OBJECTIVE: We evaluated the use of the harmonic scalpel in reducing the
      occurrence of symptomatic lymphoceles and its related complications in paraaortic
      laparoscopic lymphadenectomies (PALLs). STUDY DESIGN: All PALL that were
      performed at the Institut Claudius Regaud between January 2003 and June 2007 were
      included. Since January 2006, the harmonic scalpel has been used systematically
      for all lymphostasis. Lymphoceles that required treatment were recorded as a
      complication. RESULTS: Ninety-eight patients were enrolled, 62 PALLs were
      performed with the standard technique (control group), and 36 PALLs were
      performed with the harmonic scalpel (study group). There were no differences
      regarding operating time, blood loss, median nodal yield, and duration of
      hospital stay. Seven patients of the control group vs none of the study group (P
      = .03) experienced a symptomatic lymphocele that required medical treatment; 4
      patients had radiologic drainage, and 1 patient had surgical drainage.
      CONCLUSION: We demonstrate the efficacy of harmonic scalpel in reducing the
      occurrence of symptomatic lymphoceles in paraaortic extraperitoneal
      lymphadenectomy.

PMID- 19591971
TI  - Polymorphisms in the promoter region of the interleukin-10 (IL-10) gene in women
      with cervical insufficiency.
AB  - OBJECTIVE: Our objective was to determine whether polymorphisms in the promoter
      region of the interleukin-10 gene are more common in women with cervical
      insufficiency compared with controls. STUDY DESIGN: We conducted a case-control
      study. Histories and blood were obtained from 121 cases and 157 controls. DNA was
      extracted and purified by using Puregene kits. Samples were analyzed for the
      interleukin-10 -1082 G/A polymorphism and interleukin-10.G microsatellite in the
      interleukin-10 gene promoter region. RESULTS: The -1082 G/A polymorphism in the
      promoter region of the interleukin-10 gene occurred with similar frequency in
      cases and controls. The interleukin-10.G microsatellite contained 10 alleles (G6
      G16). The G13 allele was present more frequently in cases (24.1%) compared with
      controls (14.6%) (P = .05). CONCLUSION: Interleukin-10 is known to down-regulate
      inflammation. The G13 allele in the interleukin-10.G microsatellite occurred more
      frequently in women with cervical insufficiency compared with controls,
      suggesting that alterations in inflammatory processes may play a role in cervical
      insufficiency.

PMID- 19591972
TI  - [Papillary carcinoma in a thyroglossal duct cyst, a case report: Which
      management].
AB  - Cysts of the thyroglossal duct are common but malignant degeneration is rare,
      occurring only in 1% of the cases. The most frequent histological type is
      papillary carcinoma. The clinical presentation of these cancers is generally
      nonspecific, diagnosis being established postoperatively using the Sistrunk
      method. Debate remains open concerning appropriate management strategies and post
      therapeutic follow-up for this type of neoplasia. We report the case of a 45-year
      old patient who underwent surgery for an anterior neck mass that had developed
      over three years. Histology favored multifocal papillary carcinoma in a
      thyroglossal duct remant. Total thyroidectomy was performed. The postoperative
      protocol, established empirically due to the absence of consensus, included
      radioactive iodine and hormone suppression even though the thyroid was intact.
      After one year of follow-up, outcome has remained favorable.

PMID- 19591973
TI  - [Sinonasal adenocarcinomas reviewed. Prognostic value of WHO 2005 histological
      classification].
AB  - OBJECTIVES: The WHO 2005 histological classification separates sinonasal
      adenocarcinoma (ADC) into three classes: intestinal-type adenocarcinoma (ITAC),
      low-grade sinonasal ADC and high-grade sinonasal ADC. The goal of this study was
      to check the relevance of this classification on the prognosis of patients
      treated for ADC. PATIENTS AND METHODS: All the files of patients treated
      consecutively in the ENT department of the Montpellier University Hospital for
      ADC between 1980 and 2003 were retrospectively re-examined. Each case was
      reviewed for anatomical and pathological data based on the immunohistochemistry
      results according to the WHO 2005 classification, with a study of a panel of
      markers: cytokeratin 7 (CK7), cytokeratin 20 (CK20), Villin, CDX2 and EGFR. The
      epidemiologic data, the methods of treatment and the follow-up were studied. The
      survival probabilities were calculated using the Kaplan-Meier method and the
      survival graphs were compared using a log-rank test. RESULTS: Sixty-two files
      were reviewed. Twelve patients were reclassified into the adenoid cystic
      carcinoma category and excluded from the study. In the 50 remaining cases, there
      were 36 ITAC cases, four low-grade ADC cases and 10 high-grade dedifferentiated
      carcinomas. For all of the ADC cases, the total survival at 5 years and without
      recurrence was 64 and 52%, respectively. The analysis of the three subgroups
      showed a total survival of 72.2% for ITAC, 100% for low-grade and 20% for high
      grade ADC with a significant difference (p=0.044). This immunohistochemical
      distinction was mainly based on the expression of CK20 found in 98% of the ITAC
      cases and absent in low- and high-grade ADC patients. CONCLUSION: The WHO 2005
      classification for sinonasal ADC provides a valuable prognosis by showing a
      difference in the progression profile between ITAC, low-grade ADC and high-grade
      ADC. Moreover, broader studies should be conducted to investigate the different
      subtypes of ITAC.

PMID- 19591974
TI  - Zoledronic acid decreases bone formation without causing osteocyte death in mice.
AB  - Bisphosphonates have been associated with osteonecrosis of the jaw. The purpose
      of this study was to examine the effect of a potent bisphosphonate, zoledronic
      acid (ZA) on osteocyte viability and bone formation. Ten experimental C57BL/6
      mice were administered ZA (0.1 mg/kg-i.p.) weekly for 9 weeks while four control
      mice did not receive the drug. A pair of calcein (30 mg/kg) labels was
      administered 10 and 3 days prior to sacrifice of the 34-week-old mice. Fresh
      mandibular and femoral sections were obtained to evaluate osteocyte viability
      using a lactate dehydrogenase (LDH) assay. In addition, sections from the femur,
      mandible and maxilla were prepared for standard histomorphometry. The operator
      was blinded for data collection to eliminate bias. Data on necrotic area/total
      bone area from the LDH sections were collected. In addition, standard
      histomorphometric variables including bone formation rate were calculated. Mixed
      models were used to analyse data. The osteocytes were overwhelmingly viable and
      no necrotic areas were detected in the mandible and femur of both groups. ZA was
      not directly cytotoxic to the mouse osteocytes. There was suppression in indices
      of bone formation at all skeletal sites of the ZA group compared to the control
      group. While ZA administration in mice does not produce necrotic osteocytes, it
      severely suppresses bone formation. Such reductions can have a profound effect on
      bone healing.

PMID- 19591975
TI  - Protective role of fructose in the metabolism of astroglial C6 cells exposed to
      hydrogen peroxide.
AB  - Astroglial cells represent the main line of defence against oxidative damage
      related to neurodegeneration. Therefore, protection of astroglia from an excess
      of reactive oxygen species could represent an important target of the treatment
      of such conditions. The aim of our study was to compare the abilities of glucose
      and fructose, the two monosaccharides used in diet and infusion, to protect C6
      cells from hydrogen peroxide (H(2)O(2))-mediated oxidative stress. It was
      observed using confocal microscopy with fluorescent labels and the MTT test that
      fructose prevents changes of oxidative status of the cells exposed to H(2)O(2)
      and preserves their viability. Even more pronounced protective effects were
      observed for fructose 1,6-bis(phosphate). We propose that fructose and its
      intracellular forms prevent H(2)O(2) from participating in the Fenton reaction
      via iron sequestration. As fructose and fructose 1,6-bis(phosphate) are able to
      pass the blood-brain barrier, they could provide antioxidative protection of
      nervous tissue in vivo. So, in contrast to the well-known negative effects of
      frequent consumption of fructose under physiological conditions, acute infusion
      or ingestion of fructose or fructose 1,6-bis(phosphate) could be of benefit in
      the cytoprotective therapy of neurodegenerative disorders related to oxidative
      stress.

PMID- 19591976
TI  - Emotion words, regardless of polarity, have a processing advantage over neutral
      words.
AB  - Despite increasing interest in the interface between emotion and cognition, the
      role of emotion in cognitive tasks is unclear. According to one hypothesis,
      negative valence is more relevant for survival and is associated with a general
      slowdown of the processing of stimuli, due to a defense mechanism that freezes
      activity in the face of threat. According to a different hypothesis which does
      not posit a privileged role for the aversive system, valence, regardless of
      polarity, facilitates processing due to the relevance of both negative and
      positive stimuli for survival and for the attainment of goals. Here, we present
      evidence that emotional valence has an overall facilitatory role in the
      processing of verbal stimuli, providing support for the latter hypothesis. We
      found no asymmetry between negative and positive words and suggest that previous
      findings of such an asymmetry can be attributed to failure to control for a
      number of critical lexical variables and to a sampling bias.

PMID- 19591978
TI  - Visuospatial asymmetry and non-spatial attention in subacute stroke patients with
      and without neglect.
AB  - Asymmetry in performance and an association with non-lateralized attention are
      often mentioned as two important aspects of the clinical manifestation of
      visuospatial neglect. Both these aspects were investigated in 21 left (LH) and 24
      right hemisphere (RH) stroke patients and in 20 healthy subjects. The letter and
      star cancellation subtests of the Behavioural Inattention Task (BIT) and a
      computerized visual reaction time task (CVRT) with stimuli presented either left,
      central or right in extrapersonal space were administered. In LH patients, the
      calculation of BIT asymmetry scores allowed a better distinction between patients
      with and without neglect than raw omission scores. However, in RH patients, raw
      and asymmetry scores led to similar classifications. In the CVRT, raw and
      asymmetry scores for the number of omissions also produced identical
      classifications. Thus, the computation of asymmetry scores for omissions did not
      substantially refine the diagnosis of neglect. On the other hand, more patients
      were classified as neglect patients by using CVRT reaction time (RT) asymmetry
      scores than by using BIT or CVRT omission scores. Ipsilesional RT's were chosen
      as a measure of general, non-lateralized attention. The ipsilesional RT's of the
      LH and RH patients did not differ from the healthy subjects' lateral RT's.
      However, within the RH group, patients with both RT asymmetries and BIT scores
      above cut-off level showed longer ipsilesional RT's than patients with defective
      RT asymmetries but normal BIT scores. This supports the idea of an interaction
      between lateralized and non-lateralized attentional components in neglect, in
      which the presence of general attentional deficits exacerbates the severity of
      neglect symptoms. RT tasks may contribute to the detection of asymmetries in
      visuospatial attention in patients with subclinical neglect symptoms, who might
      compensate for their lateralized deficit in paper-and-pencil tasks employing
      intact general attention.

PMID- 19591977
TI  - Developing PFC representations using reinforcement learning.
AB  - From both functional and biological considerations, it is widely believed that
      action production, planning, and goal-oriented behaviors supported by the frontal
      cortex are organized hierarchically [Fuster (1991); Koechlin, E., Ody, C., &
      Kouneiher, F. (2003). Neuroscience: The architecture of cognitive control in the
      human prefrontal cortex. Science, 424, 1181-1184; Miller, G. A., Galanter, E., &
      Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt].
      However, the nature of the different levels of the hierarchy remains unclear, and
      little attention has been paid to the origins of such a hierarchy. We address
      these issues through biologically-inspired computational models that develop
      representations through reinforcement learning. We explore several different
      factors in these models that might plausibly give rise to a hierarchical
      organization of representations within the PFC, including an initial connectivity
      hierarchy within PFC, a hierarchical set of connections between PFC and
      subcortical structures controlling it, and differential synaptic plasticity
      schedules. Simulation results indicate that architectural constraints contribute
      to the segregation of different types of representations, and that this
      segregation facilitates learning. These findings are consistent with the idea
      that there is a functional hierarchy in PFC, as captured in our earlier
      computational models of PFC function and a growing body of empirical data.

PMID- 19591979
TI  - New insights into feature and conjunction search: I. Evidence from pupil size,
      eye movements and ageing.
AB  - Differences in the processing mechanisms underlying visual feature and
      conjunction search are still under debate, one problem being a common emphasis on
      performance measures (speed and accuracy) which do not necessarily provide
      insights to the underlying processing principles. Here, eye movements and pupil
      dilation were used to investigate sampling strategy and processing load during
      performance of a conjunction and two feature-search tasks, with younger (18-27
      years) and healthy older (61-83 years) age groups compared for evidence of
      differential age-related changes. The tasks involved equivalent processing time
      per item, were controlled in terms of target-distractor similarity, and did not
      allow perceptual grouping. Close matching of the key tasks was confirmed by
      patterns of fixation duration and an equal number of saccades required to find a
      target. Moreover, moment-to-moment pupillary dilation was indistinguishable
      across the tasks for both age groups, suggesting that all required the same total
      amount of effort or resources. Despite matching, subtle differences in eye
      movement patterns occurred between tasks: the conjunction task required more
      saccades to reach a target-absent decision and involved shorter saccade
      amplitudes than the feature tasks. General age-related changes were manifested in
      an increased number of saccades and longer fixation durations in older than
      younger participants. In addition, older people showed disproportionately longer
      and more variable fixation durations for the conjunction task specifically. These
      results suggest a fundamental difference between conjunction and feature search:
      accurate target identification in the conjunction context requires more
      conservative eye movement patterns, with these further adjusted in healthy
      ageing. The data also highlight the independence of eye movement and pupillometry
      measures and stress the importance of saccades and strategy for understanding the
      processing mechanisms driving different types of visual search.

PMID- 19591981
TI  - Polycystic ovary syndrome and cardiovascular risk in young patients treated with
      drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective,
      randomized, pilot study.
AB  - OBJECTIVE: To compare the effects of a pill containing drospirenone with those of
      a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism
      and on the surrogate markers of arterial function. SETTING: Bologna University
      School of Medicine. PATIENT(S): Thirty-seven women with polycystic ovary syndrome
      (PCOS) were randomly submitted to drospirenone+ethinylestradiol (group I; n=19)
      or combined contraceptive vaginal ring (group II; n=18) therapy. The duration of
      the study was 6 months. INTERVENTION(S): The effect of treatments was assessed
      after 6 months of therapy. MAIN OUTCOME MEASURE(S): Utero-ovarian ultrasound
      analysis and color Doppler evaluation of uterine and stromal ovarian arteries. In
      addition, analysis of brachial artery flow-mediated vasodilatation and 24-hour
      ambulatory blood pressure monitoring were performed. Fasting blood samples were
      drawn for testing biochemical and hormonal parameters and nitrites/nitrates.
      RESULT(S): Both treatments improved hirsutism, hyperandrogenemia, and ultrasound
      and color Doppler ovarian parameters. Both drospirenone+ethinylestradiol or
      contraceptive vaginal ring induced a slight but significant increase of diurnal
      and 24-hour blood pressure. Although both therapies worsened the lipid profile,
      the oral pill administration was associated with a more evident increase of
      circulating triglycerides. The 6-month treatment with the vaginal ring
      significantly improved the area under the curve for glucose, insulin, and C
      peptide, whereas the drospirenone+ethinylestradiol pill induced an increase in
      the insulinogenic index and homeostatic model assessment estimate for insulin
      resistance values. CONCLUSION(S): Vaginal hormonal contraception appears to be
      preferable to oral ethinylestradiol + drospirenone administration in
      hyperinsulinemic patients with PCOS.

PMID- 19591980
TI  - A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the
      role of polyalanine expansions in the spectrum of Mullerian fusion anomalies.
AB  - OBJECTIVE: To report a novel mutation found in a family with hand-foot-genital
      syndrome (HFGS). To characterize the genetic basis of true HFGS versus presence
      of non-HFGS-related uterovaginal septa. DESIGN: Case-control study. SETTING:
      Academic medical center. PATIENT(S): The HFGS patients and family members; women
      with uterine or uterovaginal septa without other sequelae of HFGS.
      INTERVENTION(S): Sequence analysis of HOXA13 in members of a family with HFGS (3
      affected, 1 unaffected); sequence analysis of HOXA13 in biopsy samples obtained
      from 17 non-HFGS patients with idiopathic uterine or uterovaginal septa and in 11
      normal controls. MAIN OUTCOME MEASURE(S): Presence or absence of mutations of
      HOXA13. RESULT(S): Affected members of a family with HFGS showed a novel
      expansion of the third polyalanine tract of HOXA13, inserting 10 alanines in
      frame. None of the patients with idiopathic uterovaginal septa displayed
      mutations of HOXA13. CONCLUSION(S): The cause of uterovaginal septa without hand
      and foot symptoms differs from true HFGS. When patients present with septa, it is
      not necessary to subject them to roentgenograms of the distal limbs or to
      sequence analysis of HOXA13 unless they show clear signs of the other sequelae
      characteristic of true HFGS.

PMID- 19591982
TI  - Tactile cold scissor metroplasty as a novel backup method for hysteroscopic
      metroplasty.
AB  - OBJECTIVE: To study the operative, anatomic, and functional outcome of tactile
      cold scissor metroplasty (TCSM) as a backup method for hysteroscopic metroplasty.
      DESIGN: Case series with description of the technique. SETTING: Assiut University
      Women's Health Center. PATIENT(S): Three cases with failed hysteroscopic
      metroplasty out of 127 cases with uterine septa scheduled for hysteroscopic
      resection. INTERVENTION(S): The TCSM procedure was performed in three cases under
      direct laparoscopic monitoring. MAIN OUTCOME MEASURE(S): Operative time,
      complications, hysteroscopic appearance of the cavity, reproductive outcome, and
      reintervention rates. RESULTS: The TCSM procedure was performed successfully in
      the three cases with a short total operative time (10-12 minutes). Subsequent
      office hysteroscopic appearance was satisfactory. Patients were then followed up
      for a period of time ranging from 3 to 28 months. One case had a successful
      pregnancy outcome, one has an ongoing pregnancy, and the last one did not get
      pregnant so far. CONCLUSION(S): Tactile cold scissor metroplasty is a useful,
      safe, and effective backup procedure for hysteroscopic metroplasty.

PMID- 19591983
TI  - Aromatase inhibitor for treatment of a recurrent abdominal wall endometrioma in a
      postmenopausal woman.
AB  - OBJECTIVE: Treat an abdominal wall endometrioma in a post-menopausal patient.
      DESIGN: Case report. SETTING: Academic medical center. PATIENT(S): A post
      menopausal women with a large recurrent abdominal wall endometrioma.
      INTERVENTION(S): The patient was managed with the combination of an aromatase
      inhibitor, a progestin, and serial cyst aspiration. MAIN OUTCOME MEASURE(S):
      Serum and cyst estradiol levels as well as sonographic demonstration of
      resolution. RESULT(S): Serum and cyst estradiol levels were significantly
      diminished and the cyst diminished in size. CONCLUSION(S): Taken together, this
      case demonstrates a novel approach for managing and monitoring medical therapy
      for unusual clinical presentations of endometriosis. Furthermore, it illustrates
      that endometriotic implants can be a source of circulating estrogen in
      postmenopausal women, and that this source of estrogen is generated by increased
      aromatase activity.

PMID- 19591984
TI  - Double probing individual human spermatozoa: aniline blue staining for persistent
      histones and fluorescence in situ hybridization for aneuploidies.
AB  - OBJECTIVE: To study the potential relationship between two sperm nuclear
      attributes: persistence of histones and occurrence of chromosomal aneuploidies.
      DESIGN: The two variables were examined by double probing of the same
      spermatozoa. SETTING: Academic Andrology Laboratory. PATIENT(S): Semen samples
      subjected for analyses were examined. INTERVENTION(S): We studied >58,000
      spermatozoa, in seven men, first with aniline blue histone staining, graded as
      light (mature sperm), intermediate (moderately immature), and dark (severely
      arrested maturation). After recording the staining patterns and destaining, the
      same spermatozoa were subjected to fluorescence in situ hybridization (FISH),
      using centrometric X, Y, and 17 chromosome probes. MAIN OUTCOME MEASURE(S):
      Proportions of sperm with light, intermediate, and dark staining were assessed,
      and ploidy of these sperm was evaluated. RESULT(S): The aneuploidy frequencies in
      intermediate versus light (mature) spermatozoa were increased four- to sixfold.
      In addition, aneuploidy frequencies and proportions of intermediate sperm were
      related. There was no FISH signal detectable in the darkly stained, severely
      arrested mature sperm. CONCLUSION(S): The data suggest that in sperm with
      arrested maturity and DNA fragmentation, the binding of FISH probes is
      diminished. DNA damage is further aggravated by the decondensation and
      denaturation steps of FISH. Thus, there is a strong likelihood that in
      oligozoospermic men, with a higher proportion of sperm with arrested maturation,
      the sperm disomy frequencies are historically underestimated.

PMID- 19591985
TI  - A prospective investigation into the reasons why insured United States patients
      drop out of in vitro fertilization treatment.
AB  - OBJECTIVE: To determine the primary reason why insured patients drop out of IVF
      treatment in the United States and to identify methods to decrease such behavior.
      DESIGN: Prospective patient survey. SETTING: Private infertility clinic.
      PATIENT(S): Women under the age of 40 years, who had insurance coverage for at
      least three IVF cycles, who did not conceive and who did not return to the clinic
      for a third treatment cycle. INTERVENTION(S): One hundred thirty-two eligible
      patients received a study packet of questionnaires in the mail. MAIN OUTCOME
      MEASURE(S): Subject responses to questionnaire. RESULT(S): Forty-seven subjects
      returned the questionnaire. The most common reason for terminating treatment was
      stress (39%). Subjects reported that the two main causes of stress were the toll
      that infertility took on the couples' relationship and being too anxious or
      depressed to continue. The top-rated suggestions for patient support were written
      information on how to deal with psychological stress and easy and immediate
      access to a psychologist or social worker. CONCLUSION(S): Patients undergoing IVF
      in the United States report similar reasons for terminating treatment as patients
      in Europe and Australia. However, this is the first study to gather patient
      suggestions for treating the problem.

PMID- 19591986
TI  - Maternal protein-energy and energy-restricted diets during lactation possibly
      could program folliculogenesis and the ovarian expression of leptin and its
      different isoform receptors in rats.
AB  - Both protein-energy and energy-restricted diets during lactation program the
      ovarian function of the rat offspring, leading to a reduction of
      folliculogenesis, possibly as the consequence of the altered expression of leptin
      and its isoform receptor genes.

PMID- 19591988
TI  - A man with hypogonadotropic hypogonadism successfully treated with nasal
      administration of the low-dose gonadotropin-releasing hormone analog buserelin.
AB  - OBJECTIVE: To report a patient with hypogonadotropic hypogonadism of hypothalamic
      origin successfully treated with nasal administration of a low-dose gonadotropin
      releasing hormone (GnRH) analogue. DESIGN: Case report. SETTING: A reproductive
      medical center. PATIENT(S): A 37-year-old man with anejaculation and infertility.
      INTERVENTION(S): Nasal administration of a low-dose GnRH analogue, buserelin.
      MAIN OUTCOME MEASURE(S): Semen analysis and serum levels of gonadotropins and
      testosterone after nasal buserelin use. RESULT(S): The patient's laboratory
      examination showed low serum levels of gonadotropins and testosterone. After
      being diagnosed with hypogonadotropic hypogonadism, 15 mug of buserelin acetate
      spray was administrated in each nostril three times a day (total: 90 mug/day).
      This therapy improved semen parameters and serum gonadotropin and testosterone
      levels. After approximately 1 year of this treatment, the patient's serum
      gonadotropin and testosterone levels remained in the normal range and semen
      analysis showed normozoospermia. The patient and his wife were treated with
      intracytoplasmic sperm injection, resulting in pregnancy. CONCLUSION(S): A low
      dose buserelin nasal spray appears to be an effective and well-tolerated
      therapeutic option for patients with hypogonadotropic hypogonadism of
      hypothalamic origin.

PMID- 19591987
TI  - Follicular fluid steroid hormone levels are associated with fertilization outcome
      after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To investigate the association between hormone levels from individual
      follicles and fertilization outcome among patients undergoing intracytoplasmic
      sperm injection (ICSI). Differences in concentrations of selected sex steroids
      and pituitary hormones in individual follicular aspirates between oocytes that
      fertilize successfully, those that fail to fertilize, and those that degenerate
      with ICSI were examined. DESIGN: Prospective cohort study. SETTING: Academic
      medical center. PATIENT(S): Women undergoing ovarian stimulation and ICSI.
      INTERVENTION(S): Follicular fluid was sampled by transvaginal ultrasound-guided
      aspiration of the hyperstimulated ovary. Each follicle was individually aspirated
      and collected. Intracytoplasmic sperm injection and subsequent embryo culture
      were performed using standard laboratory technique. Follicular fluid gonadotropin
      and steroid hormone levels were measured by immunoassay. MAIN OUTCOME MEASURE(S):
      Oocyte fertilization outcome with ICSI. RESULT(S): Oocytes that fertilized
      normally came from follicles with higher estradiol (adjusted odds ratio
      [AOR]=1.28) and testosterone (AOR=1.35) concentrations compared with those that
      degenerated with ICSI. Oocytes that fertilized normally also came from follicles
      with higher estradiol (AOR=1.14) and progesterone (AOR=1.09) concentrations
      compared with those that failed to fertilize. CONCLUSION(S): The hormonal profile
      of the follicular fluid yielding a degenerative egg or an egg that fails to
      fertilize is different from that resulting in normal fertilization. Higher
      follicular fluid estradiol may be a marker for oocytes that will fertilize
      normally with ICSI.

PMID- 19591989
TI  - Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect
      on assisted reproductive technology (ART) treatment and outcome.
AB  - OBJECTIVE: To evaluate factors associated with ovarian hyperstimulation syndrome
      (OHSS) and its effect on assisted reproductive technology (ART) treatment and
      outcome. DESIGN: Historic cohort study. SETTING: Clinic-based data. PATIENT(S):
      The population included 214,219 ART cycles performed during 2004 to 2006 and
      reported to the Society for Assisted Reproductive Technology Clinic Outcomes
      Reporting System Online database. The study population was limited to cycles of
      autologous, fresh embryo transfers to women without any treatment complications
      (212,041), and those developing moderate (1,523) or severe (655) OHSS.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Risk factors for developing OHSS,
      and its effect on achieving a pregnancy and live birth, as adjusted odds ratios.
      RESULT(S): Compared with white women, the risk of developing OHSS was increased
      for Black women (any OHSS, 1.88; severe OHSS, 2.93) and decreased for Hispanic
      women (any OHSS, 0.79). Ovarian hyperstimulation syndrome was associated with
      ovulation disorders (2.01), tubal factors (1.24), and unexplained factors (1.36).
      Ovarian hyperstimulation syndrome increased the odds of achieving a pregnancy
      (1.98 with any OHSS, 2.68 with severe), a live birth (any OHSS, 1.86), and a
      multiple live birth (1.58 with any OHSS, 1.86 with severe). The presence of any
      OHSS increased the risk of an adverse pregnancy outcome (stillbirth, low
      birthweight, or preterm birth) by 26% and low birthweight among singletons by
      40%. CONCLUSION(S): Ovarian hyperstimulation syndrome is associated with a higher
      likelihood of pregnancy, and multiple gestations, but also greater risks for
      adverse pregnancy outcomes.

PMID- 19591990
TI  - The use of lead follicle diameter to initiate gonadotropin-releasing hormone
      antagonist does not affect in vitro fertilization clinical pregnancy,
      implantation, or live birth rates: a prospective, randomized study.
AB  - In this prospective, randomized study, waiting for the lead follicle to reach 14
      mm before initiating GnRH antagonist administration effectively prevents an LH
      surge and ovulation during an IVF cycle. Furthermore, delaying GnRH start until
      the dominant follicle reaches 14 mm neither impacts the clinical pregnancy,
      implantation, or live birth rates nor increases the incidence of severe ovarian
      hyperstimulation syndrome.

PMID- 19591991
TI  - Fertility-preserving treatment in young women with well-differentiated
      endometrial carcinoma and severe atypical hyperplasia of endometrium.
AB  - A retrospective study on 25 women (8 with endometrial carcinoma, 17 with severe
      endometrial atypical hyperplasia) under 35 years treated with progestin showed
      that six cases (75%) in the endometrial carcinoma (EC) group and 17 (100%) in the
      atypical hyperplasia (AH) group responded to the treatment, and among the 14
      complete responders, 4 (40%) patients with AH had 7 pregnancies and 3 healthy
      deliveries. Given accurate pretreatment assessment, progestin therapy is a
      feasible management option to preserve fertility for young women with well
      differentiated endometrial carcinoma or severe atypical hyperplasia of
      endometrium.

PMID- 19591992
TI  - Sterilization of liquid nitrogen with ultraviolet irradiation for safe
      vitrification of human oocytes or embryos.
AB  - OBJECTIVE: To evaluate the efficacy of ultraviolet (UV) irradiation for rapid
      microbial decontamination of liquid nitrogen (LN2). DESIGN: Basic research.
      SETTING: Private assisted reproduction center. ANIMAL(S): Microorganisms
      (bacteria and fungi). INTERVENTION(S): Two stainless steel open dewars containing
      LN2 were contaminated in a two-step experiment with high titers of cultures of
      bacteria (Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia
      coli) and fungi (Aspergillus niger). One of the two dewars was subsequently
      exposed to UV irradiation at 253.7 nm to obtain a rapid microbial decontamination
      before the complete evaporation of LN2. MAIN OUTCOME MEASURE(S): Detection of the
      micro-organisms in LN2 after UV sterilization through the assessment of bacterial
      and fungal growth in minimal and selective Petri dishes. RESULT(S): None of the
      contaminating micro-organisms were detected in LN2 after UV sterilization.
      CONCLUSION(S): Decontamination of LN2 with UV irradiation is feasible and
      straightforward. The fact that LN2 can be quickly and safely sterilized should
      encourage the wider application of human oocyte and embryo vitrification with
      "open carriers."

PMID- 19591993
TI  - Metabolic programming of ovarian angiogenesis and folliculogenesis by maternal
      malnutrition during lactation.
AB  - OBJECTIVE: To evaluate whether maternal malnutrition during lactation programs
      ovarian folliculogenesis and the expression of vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) and its receptors KDR, Flt-1,
      and FGFR. DESIGN: Experimental study. SETTING: University-based research
      laboratory. ANIMAL(S): Adult female rats from a urogenital research laboratory.
      INTERVENTION(S): Six rat dams randomly assigned to the following groups: control
      group (C), with free access to a standard laboratory diet containing 23% protein;
      and a protein-energy-restricted group (PER), with free access to an isoenergy and
      protein-restricted diet containing 8% protein. After weaning, the female pups had
      free access to the standard laboratory diet until 90 days of age, when they were
      sacrificed at the proestrum stage. MAIN OUTCOME MEASURE(S): Quantification of
      ovarian follicles, vessels, and expression of growth factors and their receptors.
      RESULT(S): Maternal malnutrition during lactation caused a significant reduction
      in the number of primordial (C = 6.60 +/- 0.24, PER = 5.20 +/- 0.20), primary (C
      = 5.80 +/- 0.66, PER = 4.00 +/- 0.31), and Graafian follicles/section (C = 2.18
      +/- 0.29, PER = 1.08 +/- 0.37), in KDR (C = 0.22 +/- 0.04, PER = 0.09 +/- 0.01),
      Flt-1 (C = 0.28 +/- 0.05, PER = 0.12 +/- 0.02), and FGFR mRNA expression (C =
      0.34 +/- 0.05, PER = 0.13 +/- 0.05) and in the vessel density of follicles (C =
      17.26 +/- 2.30, PER = 9.96 +/- 0.97). CONCLUSION(S): Maternal malnutrition during
      lactation programs the follicular development by a reduction of VEGF and FGF mRNA
      receptors expression, probably from a direct action on the follicular development
      or a reduction in vasculature resulting in a decreased delivery of
      folliculotrophic substances in PER animals.

PMID- 19591994
TI  - Impact of chemotherapeutics and advanced testicular cancer or Hodgkin lymphoma on
      sperm deoxyribonucleic acid integrity.
AB  - OBJECTIVE: To determine the impact of combination chemotherapy on the quality of
      newly generated spermatozoa from patients with advanced testicular cancer and
      patients with Hodgkin lymphoma (HL). DESIGN: Prospective longitudinal study.
      SETTING: Academic facility. PATIENT(S): Patients with newly diagnosed metastatic
      testicular cancer and with HL that required chemotherapy were compared with age
      matched healthy community volunteers. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Semen parameters, hormone levels, testis volume, and presence of
      sperm DNA strand breaks in patients with cancer and in healthy community
      volunteers were compared before and after the patients' chemotherapy at 6, 12,
      18, and 24 months. RESULT(S): Before chemotherapy, both cancer groups had poorer
      semen quality compared with community volunteers. Among patients with testicular
      cancer and HL, 67% and 60%, respectively, had <5x10(6) sperm/mL at 6 months after
      chemotherapy. At 24 months, 60% and 57% of patients with testicular cancer and
      HL, respectively, had normal sperm concentrations. Level of FSH was significantly
      higher in the cancer group compared with community volunteers at 6 to 12 months
      after chemotherapy. Before chemotherapy, sperm DNA damage was higher in the
      cancer group than in community volunteers; this damage was increased further at 6
      months and remained elevated 24 months after treatment. CONCLUSION(S): Sperm
      generated after chemotherapy maintain a significant degree of chromatin damage.
      Therefore, survivors of testicular cancer and HL are at risk of having abnormal
      reproductive outcome. Proper counseling to these patients on reproductive risks
      and fertility preservation before chemotherapy is recommended.

PMID- 19591995
TI  - Parthenogenic activation of surplus in vitro-matured human oocytes: a tool for
      validation of oocyte cryopreservation.
AB  - Controlled-rate frozen and vitrified mature human oocytes were thawed or warmed
      and parthenogenically activated using ionomycin and 6-dimethylaminopurine to
      assess pronuclear development compared with fresh controls. This chemical
      activation model provides a useful tool for laboratories to assess proficiency
      before offering oocyte cryopreservation to their patients.

PMID- 19591996
TI  - Histologic classification of specimens from women affected by superficial
      endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas.
AB  - In this retrospective observational study involving 176 patients and 271
      biopsies, the histologic differentiation in superficial endometriosis, deeply
      infiltrating endometriosis, and ovarian endometriomas was evaluated according to
      a previously proposed classification system. Results showed a predominance of the
      undifferentiated glandular pattern (33.5%) and mixed glandular pattern (46.9%) in
      deeply infiltrating endometriosis lesions, whereas the well-differentiated
      glandular pattern (41.8%) was most frequently seen in superficial endometriosis
      lesions, and in ovarian endometriomas a predominance of both the undifferentiated
      (40.5%) and mixed patterns (37.8%) was observed.

PMID- 19591997
TI  - The relationship between follistatin and chronic low-grade inflammation in women
      with polycystic ovary syndrome.
AB  - The circulating follistatin and high-sensitivity C-reactive protein (hsCRP)
      concentrations were significantly higher in 155 Taiwanese women with polycystic
      ovary syndrome (PCOS) than in 37 healthy controls. Follistatin and hsCRP levels
      in both the PCOS and control groups were significantly correlated with each other
      independent of obesity and insulin resistance.

PMID- 19591998
TI  - Transgenerational changes in somatic and germ line genetic integrity of first
      generation offspring derived from the DNA damaged sperm.
AB  - OBJECTIVE: To report a more quantitative approach to study the influence of
      varying levels of sperm DNA damage on transgenerational changes in genomic
      instability in a mouse model. DESIGN: Experimental prospective study. SETTING:
      Embryology research laboratory. ANIMAL(S): Swiss albino mice. INTERVENTION(S):
      The sperm DNA damage was induced by different doses of gamma-irradiation to male
      mice followed by mating with healthy female mice. MAIN OUTCOME MEASURE(S):
      Genomic integrity in embryos, fetus, and spermatozoa of F1 mice derived from the
      DNA-damaged sperm. RESULT(S): The transgenerational changes in genetic integrity
      were attributed by a dose-dependent increase in the frequency of micronuclei in
      preimplantation embryos and a concomitant increase in genomic instability in
      fetal liver cells and sperm chromatin modifications in F1 males. A strong
      positive correlation was observed between the extent of sperm DNA damage and
      somatic and germ-line genomic instability. CONCLUSION(S): Sperm-mediated
      transgenerational genomic instability is dependent on the amount of DNA damage
      present in the sire's sperm at the time of fertilization.

PMID- 19591999
TI  - A comparison of the accuracy of the corpuscular fragility and mean corpuscular
      volume tests for the alpha-thalassemia 1 and beta-thalassemia traits.
AB  - OBJECTIVE: To compare the accuracy of the osmotic fragility test (OFT) and mean
      corpuscular volume (MCV) calculation when screening for the alpha-thalassemia 1
      and/or beta-thalassemia trait. METHOD: In this cross-sectional study, blood
      samples from 328 apparently healthy pregnant women were sent on the same day to
      separate laboratories for the OFT (performed using a glycerol 0.45%, phosphate
      buffered, sodium chloride solution) and MCV testing (by means of a standard
      automated hematology analyzer). A polymerase chain reaction was also performed to
      positively diagnose alpha-thalassemia 1 carriers, and a quantitative HbA(2) test
      to positively diagnose beta-thalassemia carriers. RESULTS: Sensitivity and
      specificity were 95.0% and 86% for the OFT; and based on the cut-off point of
      78.1 fL derived from the ROC curve, they were 93% and 93.4% for MCV calculation.
      The latter test was found to be slightly more accurate than the OFT in predicting
      the presence of the alpha-thalassemia 1 and/or beta-thalassemia trait.
      CONCLUSION: Both tests have high screening sensitivity for the alpha-thalassemia
      1 and/or beta-thalassemia traits, and their simplicity and very low cost make
      them attractive as screening tests for large populations. Since MCV seems to
      provide fewer false-positive results, it may be the first choice wherever an
      automated hematology analyzer calculating MCV is available.

PMID- 19592000
TI  - Interleukin-6 promoter polymorphism and cardiovascular risk factors: the Health
      2000 Survey.
AB  - OBJECTIVE: Inflammatory factors modify the risk of cardiovascular diseases and
      atherosclerosis. The single base genetic polymorphism in the promoter region of
      inflammatory cytokine interleukin-6 (IL6 -174 G>C, rs1800795) is associated with
      the variation of IL-6 production. The aim of this study was to investigate
      whether IL6 -174 G>C is associated with the risk factors and early markers of
      atherosclerosis. METHODS: As part of Finnish Health 2000 Study, we performed
      carotid artery ultrasound examinations, IL6 -174 G>C genotyping and
      cardiovascular risk factor determination for 1334 subjects aged 46-76 years.
      RESULTS: In men, serum total cholesterol was higher in IL6 -174 GG (5.70+/
      0.88mmol/L) than in the GC (5.51+/-0.98mmol/L) or CC (5.38+/-0.97mmol/L, mean+/
      SD, p=0.0059) groups. The same order was seen in LDL-C (GG 3.64+/-0.83mmol/L, GC
      3.41+/-0.88mmol/L, CC 3.30+/-0.91mmol/L, p=0.0017). The opposite association was
      observed with plasma fasting glucose levels (GG 5.93+/-0.97, GC 6.11+/-1.34, CC
      6.34+/-1.59mmol/L, p=0.043) and BMI (GG 26.8+/-3.42, GC 27.5+/-4.32, CC 28.0+/
      3.81kg/m(2), p=0.027). IL6 -174 allele C homozygous men indicated a trend towards
      higher systolic blood pressure. IL6 -174 G>C was not associated with carotid
      artery compliance, intima media thickness or CRP. The effect size of IL6 -174 G>C
      on cardiovascular risk factors was not significant in women. These results
      suggest that IL6 -174 G>C modifies the levels of several metabolic risk factors
      of atherosclerosis in men.

PMID- 19592002
TI  - Migration of bacteria through a monolith.
AB  - The separation of bacteria by electromigration techniques was a subject of
      several of our previous papers. This contribution presents the results of
      investigation of the porosity of the monolithic bed and migration of
      Staphylococcus aureus cells through it. The gigaporous monolith was thermally
      synthesized using glycidyl methacrylate, triethylene glycol dimethacrylate and
      trimethylolpropane trimethacrylate as the monomers in the presence of porogen
      solvent containing 1-decanol, polyethylene glycol and 2-methoxyethanol. The
      porous properties were evaluated by inverse size-exclusion chromatography (ISEC)
      using a wide range of polystyrene standards of different molecular weights. The
      results have shown, that large pores (ca. 300 nm) dominate in the monolithic bed
      structure, however much larger flow-through pores must also be present as ca. 1
      microm sized S. aureus bacteria were able to migrate through the bed.

PMID- 19592001
TI  - The potential protective effects of taurine on coronary heart disease.
AB  - In humans, taurine (2-aminoethanesulfonic acid) is mainly obtained from diet.
      Despite the fact that the health effects of taurine are largely unknown, taurine
      has become a popular supplement and ingredient in energy drinks in recent years.
      Evidence from mechanistic and animal studies has shown that the main biological
      actions of taurine include its ability to conjugate bile acids, regulate blood
      pressure (BP), and act as a potent antioxidant and anti-inflammatory agent. These
      actions suggest that high levels of taurine may be protective against coronary
      heart disease (CHD). However, data from epidemiologic and intervention studies in
      humans are limited. We review what is known about taurine's metabolism, its
      transportation in the body, its food sources, and evidence of its effect on
      cardiovascular health from in vitro, animal, and epidemiologic studies. We also
      discuss shortcomings of the human studies that need to be addressed in the
      future. The identification of taurine as a preventive factor for CHD may be of
      great public health importance.

PMID- 19592003
TI  - Characterisation of a proposed internet synthesis of N,N-dimethyltryptamine using
      liquid chromatography/electrospray ionisation tandem mass spectrometry.
AB  - The psychoactive properties of N,N-dimethyltryptamine (DMT) are known to induce
      altered states of consciousness in humans. These properties attract great
      interest from clinical, neuroscientific, clandestine and forensic communities.
      The Breath of Hope Synthesis was reported on an internet website as a convenient
      two-step methodology for the preparation of DMT. The analytical characterisation
      of the first stage was the subject of previous publications by the authors and
      involved the thermal decarboxylation of tryptophan and the formation of
      tryptamine. The present study reports on the characterisation of the second step
      of this procedure which was based on the methylation of tryptamine. This employed
      methyl iodide and benzyltriethylammonium chloride/sodium hydroxide as a phase
      transfer catalyst. The reaction product was characterised by liquid
      chromatography/electrospray ionisation tandem mass spectrometry and orthogonal
      acceleration time-of-flight mass spectrometry. Quantitative evaluation was
      carried out in positive multiple reaction monitoring mode (MRM), which included
      synthesis of the identified reaction products. MRM screening of the product did
      not lead to the detection of DMT. Instead, 11.1% tryptamine starting material,
      21.0% N,N,N-trimethyltryptammonium iodide (TMT) and 47.4% 1-N-methyl-TMT were
      detected. A 0.5% trace of the monomethylated N-methyltryptamine was also
      detected. This study demonstrated the impact on product purity of doubtful
      synthetic methodologies discussed on the internet.

PMID- 19592004
TI  - Diamagnetic repulsion--a versatile tool for label-free particle handling in
      microfluidic devices.
AB  - We report the exploration of diamagnetic repulsion forces for the selective
      manipulation of microparticles inside microfluidic devices. Diamagnetic materials
      such as polymers are repelled from magnetic fields, an effect greatly enhanced by
      suspending a diamagnetic object in a paramagnetic Mn(2+) solution. The
      versatility of diamagnetic repulsion is demonstrated for the trapping, focussing
      and deflection of polystyrene particles for three example applications. Firstly,
      magnet pairs with unlike poles facing each other were arranged along a
      microcapillary to trap plugs of differently functionalised particles for a
      simultaneous surface-based assay in which biotin was selectively bound to a plug
      of streptavidin coated particles utilising only 22nL of reagent. Secondly, by
      slightly modifying the magnetic field design, the rapid focussing of particles
      into a narrow central stream at a flow rate of 650microms(-1) was accomplished
      for particle pre-concentration. In a third application, 5 and 10microm
      polystyrene particles were separated from each other in continuous flow by
      passing the particle mixture through a microfluidic chamber with a perpendicular
      magnetic field, a method termed diamagnetophoresis. The separation was
      investigated between flow rates of 20-100microL h(-1), with full resolution of
      the particle populations being achieved at 20microL h(-1). These experiments show
      the potential of diamagnetic repulsion for simple, label-free manipulation of
      particles and other diamagnetic objects such as cells for a range of
      bioanalytical techniques.

PMID- 19592005
TI  - Shear induced structure additives and nonlinear pressure drop effects in
      permeable flow.
AB  - In classical flow through permeable rock, the pressure drop is linearly
      distributed through the medium. Shear induced structure materials, surfactant/co
      solute pairs, were added to retard flow in higher permeability rock samples. A
      novel core holder allows the axial pressure distribution along the flow direction
      to be measured. This enables the pressure drop to be measured as a function of
      distance along the core. The results show the spatial scale and the effect on
      pressure distribution associated with varying concentrations of shear induced
      structure additives. Subsequent flushing with water leads to restoration of the
      original flow level. The rate of recovery is dependent on the pressure of
      flushing which determines shear--showing that break up of the shear induced
      structure materials deposited in the porous rock is also dependent on shear.

PMID- 19592006
TI  - Characterization of patterned poly(methyl methacrylate) brushes under various
      structures upon solvent immersion.
AB  - In this paper we describe a graft polymerization/solvent immersion method for
      generating various patterns of polymer brushes. We used a very-large-scale
      integration (VLSI) process and oxygen plasma system to generate well-defined
      patterns of polymerized methyl methacrylate (MMA) on patterned Si(100) surfaces
      through atom transfer radical polymerization (ATRP). After immersion of wafers
      presenting lines of these PMMA brushes in water and tetrahydrofuran, we observed
      mushroom- and brush-like regimes through grafting densities and surface
      coverages, respectively, for the PMMA brushes with various pattern resolutions.
      In the mushroom-like regime, the distance between lines of PMMA brushes was
      smaller than that of the lines patterned lithographically on the wafer; in the
      brush-like regime, this distance was approximately the same. This new strategy
      allows polymer brushes to be prepared through graft polymerization and then have
      their patterns varied through solvent immersion.

PMID- 19592007
TI  - Induction of 2',3'-cyclic nucleotide 3'-phosphodiesterase in demyelination of
      BALB/c mice caused by Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis causes severe central nervous system (CNS) infection
      leading to chronic demyelinating disease. The biological role of 2',3'-cyclic
      nucleotide 3'-phosphohydrolase (CNP) in myelin-related disease requires
      investigation. CNP expression was investigated in the brain of mice at six time
      points 5-25 days post-inoculation with A. cantonensis. CNP was measured in brain
      tissue by quantitative reverse transcription polymerase chain reaction and by
      western blotting in the cerebrospinal fluid (CSF). The concentration of CNP in
      the CSF was significantly up-regulated during the severe phase of
      meningoencephalitis or meningitis as compared with controls. Immunohistochemical
      labelling localized CNP expression to the cytoplasm of oligodendrocytes. These
      results suggest that CNP in the CSF from mice with angiostrongylosis is an
      indicator of myelin destruction. Therefore, measurement of CNP in the CSF of
      patients with eosinophilic meningitis may be useful in clinical management.

PMID- 19592008
TI  - Hepatic myelolipoma and amyloidosis with osseous metaplasia in a swan goose
      (Anser cygnoides).
AB  - An adult swan goose (Anser cygnoides) kept in a zoological garden had gross
      hepatic enlargement with extensive ill-defined white foci. Microscopically, the
      hepatic lesions were composed of a mixture of adipocytes and myeloid cells. The
      goose was also affected with systemic amyloidosis and there were areas of osseous
      metaplasia associated with deposition of amyloid within the liver.

PMID- 19592009
TI  - Expression of CD44 in canine mammary tumours.
AB  - CD44 is an important adhesion molecule for hyaluronan, a major component of the
      extracellular matrix (ECM). In human breast cancer, the interaction of tumour
      cells with the ECM via CD44 is favoured as a major candidate for tumour
      progression and metastasis. The present study was designed to investigate
      immunohistochemically the expression of the standard form of CD44 in normal,
      hyperplastic and neoplastic canine mammary tissue. CD44 was expressed in normal
      and hyperplastic mammary tissue predominantly by ductal and alveolar epithelial
      cells and to a minor extent by myoepithelial cells. Stromal cells and blood
      vessels displayed low to moderate CD44 expression. In simple and complex adenomas
      and benign mixed tumours there was significant up-regulation of CD44 expression
      in alveolar epithelial cells compared with adjacent non-neoplastic mammary
      tissue. Peripheral epithelial cells of simple and complex adenomas, benign mixed
      tumours and complex carcinomas expressed significantly more CD44 compared with
      adjacent non-neoplastic mammary tissue. Peripheral epithelial cells of simple
      adenomas revealed a significantly higher CD44 expression compared with simple
      carcinomas. A statistical trend to greater CD44 expression was found in
      peripheral epithelial cells of complex adenomas, benign mixed tumours and complex
      carcinomas compared with simple carcinomas. Up-regulation of CD44 therefore
      appears to be associated with benign or relatively benign biological behaviour of
      canine mammary tumours.

PMID- 19592010
TI  - Rescuing macrophage function following severe thermal injury.

PMID- 19592011
TI  - Dexamethasone alters the hepatic inflammatory cellular profile without changes in
      matrix degradation during liver repair following biliary decompression.
AB  - BACKGROUND: Biliary atresia is characterized by extrahepatic bile duct
      obliteration along with persistent intrahepatic portal inflammation. Steroids are
      standard in the treatment of cholangitis following the Kasai portoenterostomy,
      and were advocated for continued suppression of the ongoing immunologic attack
      against intrahepatic ducts. Recent reports, however, have failed to demonstrate
      an improved patient outcome or difference in the need for liver transplant in
      postoperative patients treated with a variety of steroid regimes compared with
      historic controls. In the wake of progressive liver disease despite biliary
      decompression, steroids are hypothesized to suppress inflammation and promote
      bile flow without any supporting data regarding their effect on the emerging
      cellular and molecular mechanisms of liver repair. We have previously shown in a
      reversible model of cholestatic injury that repair is mediated by macrophages,
      neutrophils, and specific matrix metalloproteinase activity (MMP8); we questioned
      whether steroids would alter these intrinsic mechanisms. METHODS: Rats underwent
      biliary ductal suspension for 7 d, followed by decompression. Rats were treated
      with IV dexamethasone or saline at the time of decompression. Liver tissue
      obtained at the time of decompression or after 2 d of repair was processed for
      morphometric analysis, immunohistochemistry, and quantitative RT-PCR. RESULTS:
      There was a dramatic effect of dexamethasone on the inflammatory component with
      the initiation of repair. Immunohistochemistry revealed a reduction of both ED1+
      hepatic macrophages and ED2+Kupffer cells in repair compared with saline
      controls. Dexamethasone treatment also reduced infiltrating neutrophils by day 2.
      TNF-alpha expression, increased during injury in both saline and dexamethasone
      groups, was markedly reduced by dexamethasone during repair (day 2) whereas IL-6,
      IL-10, and CINC-1 remained unchanged compared with saline controls. Dexamethasone
      reduced both MMP8 and TIMP1 expression by day 2, whereas MMP9, 13, and 14 were
      unchanged compared with sham controls. Despite substantial cellular and molecular
      changes during repair, collagen resorption was the same in both groups
      CONCLUSION: Dexamethasone has clear effects on both the hepatic macrophage
      populations and infiltrating neutrophils following biliary decompression. Altered
      MMP and TIMP gene expression might suggest that steroids have the potential to
      modify matrix metabolism during repair. Nevertheless, successful resorption of
      collagen fibrosis proceeded presumably through other MMP activating mechanisms.
      We conclude that steroids do not impede the rapid intrinsic repair mechanisms of
      matrix degradation required for successful repair.

PMID- 19592012
TI  - Meshomania.

PMID- 19592013
TI  - Pediatric FAST and elevated liver transaminases: an effective screening tool in
      blunt abdominal trauma.

PMID- 19592015
TI  - Development of quality indicators of care for patients undergoing hepatic
      resection for metastatic colorectal cancer using a Delphi process.
AB  - BACKGROUND: Very few quality indicators of care exist for surgical procedures.
      These may be used to both score the quality of care received, and as a method of
      improving the quality of care delivered (quality improvement initiatives).
      MATERIALS AND METHODS: The goal of this study was to develop a set of evidence
      based quality indicators by expert consensus for patients undergoing hepatic
      resection of colorectal metastases to the liver. A Delphi approach was used to
      develop a set of evidence-based quality indicators for patients undergoing
      hepatic resection of colorectal metastases to liver. A panel of experts was
      formed through nomination by members of the Canadian Hepatopancreaticobiliary
      Society (CHPBS). The Delphi process consisted of three iterations of
      questionnaires. During each round, the panel members were asked to score the
      potential indicators and suggest any new indicators. RESULTS: A list of 70
      potential indicators was generated from the literature, of which 27 achieved
      consensus for inclusion in the final list of quality indicators. After
      consolidating similar or redundant indicators, the final list had 18 quality
      indicators. All of the indicators in the final list were from our original
      literature search. CONCLUSIONS: This Delphi process has used the best available
      evidence, along with a consensus methodology employing the opinion of experts in
      the field, to identify 18 quality indicators for patients undergoing hepatic
      resection for metastatic colorectal cancer. These indicators will provide a means
      for benchmarking quality of care among surgeons, institutions, and health
      regions.

PMID- 19592014
TI  - Transplantation of adrenal cortical progenitor cells enriched by Nile red.
AB  - BACKGROUND: The adrenal cortex may contain progenitor cells useful for tissue
      regeneration. Currently there are no established methods to isolate these cells.
      MATERIAL AND METHODS: Murine adrenal cells were sorted into a Nile-red-bright
      (NR(bright)) and a Nile-red-dim (NR(dim)) population of cells according to their
      degree of cholesterol content revealed by Nile red fluorescence. The cells were
      transplanted under the renal capsule to determine their ability for regeneration.
      RESULTS: The NR(bright) cells contained an abundance of lipid droplets, whereas
      the NR(dim) cells contained little. The NR(bright) cells expressed Sf1 and the
      more differentiated adrenal cortical genes, including Cyp11a1, Cyp11b1, and
      Cyp11b2, whereas the NR(dim) cells expressed Sf1 but not the more differentiated
      adrenal cortical genes. After 56 d of implantation in unilateral adrenalectomized
      mice, the NR(dim) cells expressed Sf1 and the more differentiated adrenal
      cortical genes, whereas the NR(bright) cells ceased to express Sf1 as well as the
      more differentiated adrenal cortical genes. NR(dim) cells also proliferated in
      the presence of basic fibroblast growth factor. CONCLUSIONS: The population of
      NR(dim) cells contained adrenal cortical progenitor cells that can proliferate
      and give rise to differentiated daughter cells. These cells may be useful for
      adrenal cortical regeneration.

PMID- 19592016
TI  - Protective effect of rutin on the ischemia/reperfusion induced damage in rat
      kidney.
AB  - Reactive oxygen species (ROS) are suggested to participate in
      ischemia/reperfusion (I/R) injury in the kidney. This study was designed to
      investigate the effect of rutin, a bioflavonoid, in I/R induced renal injury.
      Wistar albino rats were unilaterally nephrectomized, and 2 wk later they were
      subjected to 45 min of left renal pedicle occlusion followed by 3h of
      reperfusion. Either rutin (1g/kg) or saline was administrated (i.p.) 1h prior to
      ischemia. At the end of the reperfusion period, kidney samples were taken for
      determination of renal malondialdehyde (MDA) and glutathione (GSH) levels,
      manganese-superoxide dismutase (MnSOD) activity and histological examination.
      Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH)
      concentrations were measured for the evaluation of renal function. I/R caused a
      significant decrease in GSH level and MnSOD activity, which was accompanied by a
      significant increase in MDA level of kidney tissues. Similarly, serum BUN and
      creatinine levels, as well as LDH were elevated in the I/R group compared with
      the control group. Pretreatment of rats with rutin (1g/kg/ i.p.) significantly
      attenuated renal dysfunction, reduced elevated MDA levels, and restored the
      depleted MnSOD activity and GSH levels. These beneficial changes in the
      biochemical parameters were also associated with parallel changes in
      histopathological appearance. These findings suggest that ROS play a causal role
      in I/R induced renal injury, and that rutin exerts renal-protective effects,
      probably by inhibiting ROS and antioxidant activities.

PMID- 19592017
TI  - Hepatic regenerative response in small-sized liver isografts in the rat.
AB  - BACKGROUND: To investigate hepatic regenerative response and associated
      mechanisms in different-size liver grafts in the rat. METHODS: Rat models of
      different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were
      established, with a sham operation group serving as a control. Portal pressure,
      graft injury, interleukin 6 (IL-6), signal transducer and activator of
      transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and
      proliferating cell nuclear antigen (PCNA) were all assessed. RESULTS: The portal
      pressure was significantly higher and hepatic injury more severe in the smaller
      sized groups than in the whole graft group, especially in the 30%-size grafts.
      Hepatic IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in the two
      smaller sized groups were significantly higher than in the whole graft group,
      while IL-6 levels appeared to be negatively associated with graft sizes.
      Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA
      expression were also markedly increased in the small-sized grafts compared with
      the whole grafts, and appeared to positively correlate with early measurements of
      portal pressure and subsequent hepatic injury. CONCLUSION: Vigorous hepatic
      regeneration in small-for-size liver grafts may be associated with highly
      activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft
      size, portal pressure, and hepatic injury.

PMID- 19592018
TI  - Gender-dependent differential phosphorylation in the ERK signaling pathway is
      associated with increased MMP2 activity in rat aortic smooth muscle cells.
AB  - BACKGROUND: The present experiments were conducted to explore the role of mitogen
      activated protein kinase (MAPK) pathways, potential upstream regulators of MMPs,
      in abdominal aortic aneurysms (AAAs). METHODS: Rat aortic smooth muscle cells
      (RASMCs) from males and females were treated with media containing interleukin
      (IL)-1beta (2 ng/mL), a concentration known to be present in AAAs. Levels of both
      total and phosphorylated (activated) extracellular signal-regulated kinase (ERK),
      c-Jun amino terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38
      were examined by Western blotting at various time intervals up to 60 min. Similar
      experiments were conducted following exposure of RASMCs to elastase (6 U/mL), a
      concentration known to induce AAA formation in rodents. Finally, media was
      assayed for MMP activity by zymography. RESULTS: Total ERK (t-ERK) was
      consistently no different in females compared with males prior to or following IL
      1beta exposure. In contrast, levels of phosphorylated ERK (p-ERK) were
      significantly higher in males than females throughout the postexposure period (P
      < 0.0001). Levels of t-p38, p-p38, and t-JNK were not altered in a gender
      dependent manner. The lack of p-JNK levels detected in both male and female
      RASMCs did not allow for conclusions to be drawn regarding gender disparities in
      this pathway. Results were similar following RASMC elastase exposure, although t
      ERK levels were consistently higher in females than males (P < 0.0001). Pro-MMP2
      levels were significantly higher (P = 0.0035) in males than females at each time
      point following elastase exposure. CONCLUSIONS: These data provide evidence
      implicating alterations in p-ERK signaling via the up-regulation of MMPs as a
      potential explanation for gender-related discrepancies in AAA formation.

PMID- 19592019
TI  - Outcomes of aortic valve replacement performed by residents in octogenarians.
AB  - BACKGROUND: Aortic valve replacement (AVR) traditionally carries a significant
      risk in elderly patients. We evaluated the outcomes of AVR in octogenarian
      patients in the context of surgical education. METHODS: A retrospective review of
      all AVR operations (n=23) performed by residents at a single academic institution
      between May 1992 and May 2007 on patients who were >/=80 y old. RESULTS: All
      patients were men (mean age, 83+/-2.5 y). The predominant valve disease was
      aortic stenosis. Comorbidities included coronary artery disease (n=15), New York
      Heart Association class III/IV congestive heart failure (n=15), hypertension
      (n=17), diabetes (n=5), chronic obstructive pulmonary disease (n=5), peripheral
      vascular disease (n=6), and cerebrovascular disease (n=3). Major postoperative
      morbidity included cerebrovascular accident (n=1), mediastinitis (n=1),
      reoperation for bleeding (n=1), and respiratory failure (n=3; 2 required a
      tracheostomy). There were no operative deaths. The mean length of total hospital
      stay (to home discharge) after AVR was 36+/-45 d, of which 19+/-14 d were spent
      in an acute surgical care unit. Follow-up was complete; the 1-, 3-, and 5-y
      survival rates were 96%, 86%, and 55%, respectively. CONCLUSIONS: Supervised
      residents can safely perform AVR on octogenarian patients and achieve good
      outcomes.

PMID- 19592020
TI  - Noninvasive electromagnetic fields on keratinocyte growth and migration.
AB  - BACKGROUND: Although evidence has shown that very small electrical currents
      produce a beneficial therapeutic result for wounds, noninvasive electromagnetic
      field (EMF) therapy has consisted mostly of anecdotal clinical reports, with very
      few well-controlled laboratory mechanistic studies. In this study, we evaluate
      the effects and potential mechanisms of a noninvasive EMF device on skin wound
      repair. MATERIALS AND METHODS: The effects of noninvasive EMF on keratinocytes
      and fibroblasts were assessed via proliferation and incisional wound model
      migration assays. cDNA microarray and RT-PCR were utilized to assess genetic
      expression changes in keratinocytes after noninvasive EMF treatment. RESULTS: In
      vitro analyses with human skin keratinocyte cultures demonstrated that
      noninvasive EMFs have a strong effect on accelerating keratinocyte migration and
      a relatively weaker effect on promoting keratinocyte proliferation. The positive
      effects of noninvasive EMFs on cell migration and proliferation seem keratinocyte
      specific without such effects seen on dermal fibroblasts. cDNA microarray and RT
      PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated
      keratinocytes. CONCLUSIONS: This study suggests that a noninvasive EMF
      accelerates wound re-epithelialization through a mechanism of promoting
      keratinocyte migration and proliferation, possibly due to upregulation of CRK7
      and HOXC8 genes.

PMID- 19592022
TI  - A population-based analysis of 1037 malignant ovarian tumors in the pediatric
      population.
AB  - BACKGROUND: Concerns of malignant potential have impacted the utilization of
      ovarian salvage for treatment of ovarian masses in children. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) registry was analyzed for all
      females < or =19 y diagnosed with an ovarian tumor between 1973 and 2005.
      RESULTS: Overall, 1037 pediatric patients with ovarian tumors were identified.
      Approximately 61.7% of tumors occurred in patients 15 to 19 y old. The age
      adjusted incidence of all malignant pediatric ovarian tumors in those < or =9 y
      was 0.102 versus 1.072 per 100,000 in those aged 10 to 19 y. The majority of
      cases (57.4%) present at an early localized stage. The predominant pathology was
      germ cell tumors in all age groups (77.4%). Overall 5- and 10-y survival rates
      are 91.7% and 91.4%, respectively. By multivariate analysis, advanced disease
      stage (HR 3.17, P<0.001), lack of surgery (HR 4.49, P =0.039), and poorly
      differentiated tumors (HR 3.40, P=0.011) were associated with worse outcomes.
      CONCLUSIONS: Malignant ovarian tumors are rare, particularly in patients under 5
      y of age. Furthermore, the most common histologies are of low metastatic
      potential and carry high cure rates. Thus, the surgeon should implement ovarian
      sparing strategies on the affected ovary unless a malignancy is clearly suspected
      and conserve the contralateral ovary in all children.

PMID- 19592021
TI  - Proteomic analysis of neuroblastoma microenvironment: effect of the host-tumor
      interaction on disease progression.
AB  - BACKGROUND: Children with advanced-stage neuroblastoma (NB) traditionally
      experience poor outcomes. Because early detection of advanced-stage disease may
      impact survival, finding new targets for early diagnosis is crucial. Evidence
      suggests the tumor microenvironment may have profound effects on cancer
      progression. METHODS: As little is known concerning the NB-host microenvironment,
      this study applied proteomic techniques, two-dimensional polyacrylamide gel
      electrophoresis (2D PAGE) combined with matrix assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry to determine protein
      differences between cell cultured NB and tumors grown in mice for 2, 4, and 5 wk.
      RESULTS: We found an increase in proteins in cultured NB compared with implanted
      mouse tumors during tumor progression. Additionally, analyzing in vivo tumors to
      cultured NB, we observed less expressed proteins. However, 16 out of 19 proteins
      were of mouse origin, thus inferring host-derived factors contributing to tumor
      growth. CONCLUSION: We show that the dynamic relationship between NB and host
      microenvironment is important for tumor growth and better understanding of this
      milieu maybe relevant towards finding unique approaches for identifying advanced
      stage disease.

PMID- 19592023
TI  - Surgical resection of hepatocellular carcinoma: less is more?

PMID- 19592024
TI  - The protective mechanism of ligustrazine against renal ischemia/reperfusion
      injury.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is unavoidable in renal
      transplantation, and represents an additional risk factor for the late renal
      allograft failure. Our study focused on the effects of ligustrazine on oxidative
      stress, apoptosis, neutrophils recruitment, the expression of proinflammatory
      mediators and adhesion molecules caused by renal I/R injury. MATERIALS AND
      METHODS: Renal warm I/R was induced in male C57BL/6 mice by clamping the left
      renal artery and vein non-traumatically. Group I was sham-operated animals; group
      II, nontreated animals; and group III, ligustrazine-treated animals (80 mg/kg,
      i.p. 30 min before I/R). Mice were sacrificed 4 and 24h post reperfusion. The
      effects of ligustrazine on oxidative stress, neutrophils recruitment,
      proinflammatory mediators, and adhesion molecules caused by renal I/R injury were
      assayed. RESULTS: Ligustrazine pretreatment attenuated dramatically the injuries
      in mice kidneys caused by warm I/R (histological scores of untreated versus
      treated, 4.2 +/- 0.4 versus 0.9 +/- 0.3; P<0.01). Administration of ligustrazine
      significantly reduced myeloperoxidase (MPO) activity by 38.6% and decreased
      malondialdehye (MDA) level by 19.2%, while superoxide dismutase (SOD) activity
      increased by 39.6% (P<0.01), suggesting an effective reduction of oxidative
      stress following ligustrazine treatment. Moreover, ligustrazine also inhibited
      cell apoptosis, abrogated neutrophils recruitment, and suppressed the over
      expression of TNF-alpha and ICAM-1. CONCLUSIONS: In conclusion, ligustrazine
      protects murine kidney from warm ischemia/reperfusion injury, probably via
      reducing oxidative stress, inhibiting cell apoptosis, decreasing neutrophils
      infiltration, and suppressing the overexpression of TNF-alpha and ICAM-1 levels.

PMID- 19592025
TI  - The choice of anesthesia influences oxidative energy metabolism and tissue
      survival in critically ischemic murine skin.
AB  - In surgical animal studies anesthesia is used regularly. Several reports in the
      literature demonstrate respiratory and cardiovascular side effects of
      anesthesiologic agents. The aim of this study was to compare two frequently used
      anesthesia cocktails (ketamine/xylazine [KX] versus
      medetomidine/climazolam/fentanyl [MCF]) in skin flap mouse models. Systemic blood
      values, local metabolic parameters, and surgical outcome should be analyzed in
      critical ischemic skin flap models. Systemic hypoxia was found in the animals
      undergoing KX anesthesia compared with normoxia in the MCF group (sO(2): 89.2% +/
      2.4% versus 98.5% +/- 1.2%, P < 0.01). Analysis of tissue metabolism revealed
      impaired anaerobic oxygen metabolism and increased cellular damage in critical
      ischemic flap tissue under KX anesthesia (lactate/pyruvate ratio: KX 349.86 +/-
      282.38 versus MCF 64.53 +/- 18.63; P < 0.01 and glycerol: KX 333.50 +/- 83.91
      micromol/L versus MCF 195.83 +/- 29.49 micromol/L; P < 0.01). After 6 d,
      different rates of flap tissue necrosis could be detected (MCF 57% +/- 6% versus
      KX 68% +/- 6%, P < 0.01). In summary we want to point out that the type of
      anesthesia, the animal model and the goal of the study have to be well
      correlated. Comparing the effects of KX and MCF anesthesia in mice on surgical
      outcome was a novel aspect of our study.

PMID- 19592026
TI  - Influence of red blood cell transfusion on CD4+ T-helper cells immune response in
      patients undergoing cardiac surgery.
AB  - BACKGROUND: Both surgical insult and red blood cell transfusion (RBCT) induce
      alterations in type-1/type-2, CD4T-helper cell balance. This study was aimed to
      determine the influence of RBCT on Th1 and Th2 function immune response in
      cardiac surgery patients. MATERIAL AND METHODS: Three blood samples were
      prospectively drawn from 81 cardiac surgery patients with cardiopulmonary bypass
      (CPB): preoperatively (preOP), during CPB, before RBCT (intraOP), and on
      postoperative day 1 (postOP). Immune response was assessed by flow cytometry
      measurement of the proportion of CD4(+)T-helper cells producing tumor necrosis
      factor (TNF)-alpha [Th1 response] and interleukin (IL)-10 [Th2 response].
      RESULTS: Sixty-two patients were transfused (3.4 +/- 2.3 units/patient), whereas
      19 did not. Both groups were homogeneous, both at baseline and during surgery,
      regarding multiple perioperative clinical and laboratory variables, but
      postoperative blood loss and transfused RBC units were significantly higher in
      transfused versus nontransfused patients. In contrast, preoperative hemoglobin
      was significantly higher in nontransfused patients. CD4(+)T-helper cells
      significantly decreased in both groups of patients from preOP to intraOP 1 and
      from intraOP to postOP. In nontransfused patients, there were no significant
      changes in CD4(+)T-helper cells expressing TNFalpha or IL-10 among different
      sampling times. In contrast, RBCT resulted in a significant increment in Th2
      response from intraOP to postOP (P=0.01), without affecting Th1 response.
      CONCLUSION: RBCT, but not surgery or CPB, induces a shift of the Th1/Th2 balance
      toward Th2 dominance.

PMID- 19592027
TI  - Early loss of heart rate complexity predicts mortality regardless of mechanism,
      anatomic location, or severity of injury in 2178 trauma patients.
AB  - BACKGROUND: Reduced heart rate (HR) complexity (e.g., a lack of randomness or
      unpatterned variability) is an established predictor of trauma patient mortality.
      However, this finding has not been validated across the diverse spectrum of
      traumatic injury, and underlying mechanisms of this relationship are poorly
      understood. MATERIALS AND METHODS: Two thousand one hundred seventy-eight trauma
      patients were admitted directly to the intensive care unit (ICU), and had
      sufficient (>6h) continuous integer heart rate data within the first d. Patients
      were stratified by location of isolated severe injury (head, torso, both, or
      neither), primary mechanism (blunt or penetrating), and probability of survival,
      an accepted scoring system based on age, admission vital signs, and injury type
      and severity. HR multiscale entropy (MSE) was calculated (sum of scales, Costa's
      algorithm, physionet.org, m=2, r=0.15) to estimate complexity. Univariate
      analysis was performed by comparing MSE between survivors and nonsurvivors in
      each subgroup. Multivariate analysis incorporated logistic regression to
      characterize the relationship between MSE and risk of death, controlling for
      probability of survival. The MSE odds ratios (OR) and area under the receiver
      operator curve (AUC) were calculated. RESULTS: Reduced MSE was significantly
      associated with increasing mortality, and was independent of probability of
      survival in all multivariate analyses (OR 0.87-0.94). This range of odds ratios
      implies that a patient with an MSE of 15 has roughly a 2- to 6-fold increase in
      odds of death versus a patient with an MSE of 25. The relationship between MSE
      and death was moderately stronger in patients with isolated severe head injury
      versus torso injury, and significantly stronger in patients with penetrating
      versus blunt mechanism of injury. MSE measured early in the hospital stay
      remained a robust predictor of mortality in all subgroups, even stratified by
      narrow ranges of probability of survival. CONCLUSIONS: Early reduction of heart
      rate complexity is an important risk factor across diverse injury etiology. This
      suggests common underlying physiologic mechanisms linking the loss of biologic
      complexity to death.

PMID- 19592028
TI  - Revisiting adrenal mass size as an indication for adrenalectomy.
AB  - BACKGROUND: Diagnostic tests that can accurately differentiate between benign and
      malignant adrenal lesions are lacking. Mass size is currently utilized as an
      indication for adrenalectomy in patients with adrenal masses. However, the
      accuracy of this criterion and the ideal size threshold are unclear. The aim of
      the present study was to determine the frequency of using mass size as the only
      indication for adrenalectomy and the ideal size threshold for distinguishing
      malignant primary adrenal tumors from lesions that do not require surgical
      resection. PATIENTS AND METHODS: The adrenalectomy database of the University of
      Wisconsin was retrospectively reviewed. Patients undergoing adrenalectomy for
      adrenal mass lesions were identified. Student's t-test and Fisher's exact test
      were used to compare continuous and noncontinuous variables respectively, with P<
      or =0.05 representing significance. RESULTS: Of 198 adrenalectomies performed
      between 1989 and 2007, 106 met inclusion criteria. There were no differences in
      age or gender distribution between patients with malignant and benign lesions.
      After complete clinical, imaging, and biochemical evaluation, mass size was the
      only indication for 16 adrenalectomies (15.1%). Adrenal mass size in these
      patients ranged from 3.3 to 14 cm (mean 5.9+/-0.6 cm). Only three of these
      lesions (18.8%) proved malignant. In total, eight malignant tumors were
      identified in this series (7.5%, size range 4-14 cm, mean 8.0+/-1.3 cm). Benign
      and non-neoplastic lesions accounted for the remaining masses (92.5%, size range
      0.7-9.3 cm, mean 3.6+/-0.2 cm) and were significantly smaller than malignant
      lesions (P<0.001). CONCLUSION: Adrenal mass size is the only indication for
      adrenalectomy in a substantial number of patients. A size cut-off of 4 cm would
      have led to resection of all primary malignant adrenal tumors in this series and
      reduced the number of adrenalectomies for benign disease.

PMID- 19592029
TI  - Premedication with dexmedetomidine alone or together with 0.5% lidocaine for
      IVRA.
AB  - BACKGROUND: This study aimed to compare the effects of low and same dose of
      dexmedetomidine when added to lidocaine for intravenous regional anesthesia
      (IVRA) and when administered for premedication before IVRA. MATERIAL AND METHODS:
      In this double blind study, 45 patients with ASA physical status I-II were
      scheduled to undergo carpal tunnel release as an outpatient procedure and were
      randomly divided into three groups. IVRA was performed with 40 mL of 0.5%
      lidocaine in the operating room. A single dose of dexmedetomidine 0.5 MUg/kg and
      placebo (saline) solution in a total volume of 20 mL were administered
      intravenously to group P (n=15) and group S (n=15), respectively, before IVRA.
      0.5 MUg/kg of dexmedetomidine was added to lidocaine in group A (n=15) during
      IVRA. The onset and recovery time of sensory and motor block, intraoperative
      postoperative visual analog scale (VAS) and Ramsay sedation scores (RSS),
      analgesic requirement, hemodynamic variables, and side effects were noted.
      RESULTS: Significantly shortened sensory block onset and recovery time in group P
      and A, shortened motor block onset time in group P, and decreased intra
      postoperative VAS scores and analgesic requirement in groups P and A were found.
      Intraoperative RSS in group P and postoperative RSS in groups P and A were higher
      than in group S. Intraoperative and postoperative heart rate and postoperative
      mean arterial blood pressure (MAP) of group P was significantly lower than groups
      A and group S, respectively. CONCLUSION: Both addition of dexmedetomidine to
      lidocaine and premedication with dexmedetomidine for IVRA similarly improve
      quality of anesthesia and perioperative analgesia without important side effects.

PMID- 19592030
TI  - Tumor-derived pancreatic stellate cells promote pancreatic cancer cell invasion
      through release of thrombospondin-2.
AB  - BACKGROUND: Tumor derived pancreatic stellate cells (TDPS) cells are key cellular
      components of the pancreatic tumor microenvironment. These stellate cells can
      release growth factors, proteases, and extracellular matrix proteins that may
      stimulate the spread of pancreatic cancer. We sought to determine whether TDPS
      cells promote the local invasion of pancreatic cancer cells and mechanisms
      involved. METHODS: TDPS and panc-1 cells were grown in coculture to determine
      directional migration and panc-1 invasiveness was quantified using Matrigel
      invasion chambers, comparing TDPS cells to human foreskin fibroblasts (HFFs).
      ELISA was used to determine the secretion of growth factors, proteases, and
      extracellular matrix proteins from TDPS cells and HFFs, and then siRNAs used to
      knockdown expression of factors. RESULTS: In coculture panc-1 cells migrate
      toward TDPS cells, creating nests of cancer cells within the stromal cells. TDPS
      cells promote the invasion of panc-1 cells and release thrombospondin 2 (TSP-2),
      whereas HFFs did not. When TSP-2 expression is reduced in TDPS cells using
      selective siRNAs, pancreatic cancer cell invasion was inhibited. CONCLUSION:
      Tumor-derived pancreatic stellate cells stimulate pancreatic cancer cell
      invasion, likely through release of TSP-2. Targeting pro-invasive elements, such
      as TSP-2, within the tumor microenvironment may inhibit local invasion, thus
      permitting more patients to undergo curative resection of pancreatic cancer.

PMID- 19592031
TI  - Metabonomics: a useful tool for the future surgeon.
AB  - BACKGROUND: In the past decade or so, a range of technologies have emerged that
      have shown promise in increasing our understanding of disease processes and
      progression. These advances are referred to as the "omics" technologies;
      genomics, transcriptomics, and proteomics. More recently, another "omics"
      approach has come to the fore: metabonomics, and this technology has the
      potential for significant clinical impact. Metabonomics refers to the analysis of
      the metabolome, that is, the metabolic profile of a system. The advantage of
      studying the metabolome is that the end points of biological events are
      elucidated. RESULTS: Although still in its infancy, the metabonomics approach has
      shown immense promise in areas as diverse as toxicology studies to the discovery
      of biomarkers of disease. It has also been applied to studies of both renal and
      hepatic transplants. Metabolome analysis may be conducted on a variety of
      biological fluids and tissue types and may utilize a number of different
      technology platforms, mass spectrometry (MS) and nuclear magnetic resonance (NMR)
      spectroscopy being the most popular. In this review, we cover the background to
      the evolution of metabonomics and its applications with particular emphasis on
      clinical applications. CONCLUSIONS: We conclude with the suggestion that
      metabonomics offers a platform for further biomarker development, drug
      development, and in the field of medicine.

PMID- 19592032
TI  - Pancreatic resection in octogenarians.
AB  - BACKGROUND: Few studies exist that evaluate outcomes of pancreatectomy in
      patients > or =80 y of age, an age group increasing in size in the United States.
      This study analyzes the outcomes of pancreatectomy in patients > or =80 y of age.
      METHODS: The medical records of 32 patients > or =80 y of age undergoing
      pancreatectomy at our institution from April 1995 through October 2008 were
      reviewed, and outcomes were analyzed. RESULTS: The median patient age was 82 y,
      and 75% were ASA Class 3. Eighty-one percent of the resections were
      pancreaticoduodenectomies. There were no operative deaths. Sixty-six percent of
      patients suffered at least one complication. The median length of stay was 11 d.
      Eighty-one percent of the resections were performed for cancer. Median survival
      for all patients was 14.4 mo. Median survival for patients with cancer was 12 mo
      versus 103 mo for patients without cancer, P = 0.017. CONCLUSIONS: Pancreatectomy
      in patients > or =80 y of age can be performed with a low risk of mortality but
      with significant morbidity.

PMID- 19592033
TI  - Pediatric FAST and elevated liver transaminases: An effective screening tool in
      blunt abdominal trauma.
AB  - BACKGROUND: The current standard for the evaluation of children with blunt
      abdominal trauma (BAT) consists of physical examination, screening lab values,
      and computed tomography (CT) scan. We sought to determine if the focused
      assessment with sonography for trauma (FAST) combined with elevated liver
      transaminases (AST/ALT) could be used as a screening tool for intra-abdominal
      injury (IAI) in pediatric patients with BAT. METHODS: Registry data at a level 1
      trauma center was retrospectively reviewed from 1991-2007. Data collected on BAT
      patients under the age of 16 y included demographics, injury mechanism, ISS, GCS,
      imaging studies, serum ALT and AST levels, and disposition. AST and ALT were
      considered positive if either one was >100 IU/L. RESULTS: Overall, 3171 cases
      were identified. A total of 1008 (31.8%) patients received CT scan, 1148 (36.2%)
      had FAST, and 497 (15.7%) patients received both. Of the 497 patients, 400
      (87.1%) also had AST and ALT measured. FAST was 50% sensitive, 91% specific, with
      a positive predictive value (PPV) of 68%, negative predictive value (NPV) of 83%,
      and accuracy of 80%. Combining FAST with elevated AST or ALT resulted in a
      statistically significant increase in all measures (sensitivity 88%, specificity
      98%, PPV 94%, NPV 96%, accuracy 96%). CONCLUSIONS: FAST combined with AST or ALT
      > 100 IU/L is an effective screening tool for IAI in children following BAT.
      Pediatric patients with a negative FAST and liver transaminases < 100 IU/L should
      be observed rather than subjected to the radiation risk of CT.

PMID- 19592035
TI  - Decrease in wound tensile strength following post-surgical estrogen replacement
      therapy in ovariectomized rats during the early phase of healing is mediated via
      ER-alpha rather than ER-beta: a preliminary report.
AB  - BACKGROUND: In cases of acute surgery or trauma, the most effective method of
      increasing the level of estrogen in postmenopausal women is its administration
      immediately pre- or postsurgery. However, in our previous study (J Surg Res 2008;
      147:117-122) we showed that postsurgical administration of nonspecific estrogen
      receptor (ER) agonist decreases wound tensile strength. Therefore, the aim of
      this study was to evaluate whether this effect is mediated via the alpha or beta
      ER. MATERIALS AND METHODS: Three months prior to the wound healing experiment, 18
      rats were anesthetized and underwent ovariectomy (OVX), while another six rats
      were sham operated. Two parallel full thickness skin incisions were performed on
      the back of each rat. Doses of 1mg/kg of either PPT (ER-alpha agonist) or DPN (ER
      beta agonist) were administered to 12 OVX rats for 6 d postoperatively, whereas
      all other animals received vehicle. After 6 d, all animals were sacrificed and
      samples removed for wound tensile strength measurement and histologic evaluation.
      RESULTS: The mean wound tensile strength of PPT-treated rats (6.8+/-1.9 g/mm2)
      was significantly lower compared with all other groups (P<0.05). No significant
      differences were observed between DPN-treated (8.9+/-2.2 g/mm2), non-OVX vehicle
      treated (8.7+/-2.0 g/mm2), and OVX vehicle-treated (9.1+/-1.7 g/mm2) rats.
      Nevertheless, no remarkable differences were found between groups during
      histologic evaluation. CONCLUSION: Our results indicate that the wound tensile
      strength decrease is mediated through the alpha rather than beta ER.

PMID- 19592034
TI  - Properties of extracellular matrix-like scaffolds for the growth and
      differentiation of endothelial progenitor cells.
AB  - BACKGROUND: To provide a new strategy for constructing small vascular graft, the
      survival conditions of endothelial progenitor cells (EPCs), which were seeded on
      two different groups of extracellular matrix (ECM) scaffolds were studied in
      vitro. MATERIALS AND METHODS: The scaffold was made with a mixture of fibrinogen,
      fibronectin, and laminin, which solidified to form unpressed structure. A 1N
      force could make it to be pressed. EPCs induced from cultures of rat mesenchymal
      stem cells were seeded on two different groups of ECM scaffolds: (1) pressed
      scaffolds; and (2) unpressed scaffolds. The survival conditions of cells on the
      two groups of scaffolds were reflected by properties below: cell attachment and
      proliferation detected by cell counting; differentiation of EPCs detected by
      changes in the cell morphology and the expression of endothelial marker von
      Willebrand factor (VWF) using immunofluorescence, immuno-blot, and real-time PCR;
      the two different scaffolds were characterized for their surface ultra-structures
      by SEM, and torques by a rheometer. RESULTS: The cells grew faster on the pressed
      scaffold (P<0.001) for the first 7 d. Furthermore, cells on the pressed scaffolds
      displayed more uniform shapes with morphology resembling that of endothelial
      cells than those on the unpressed scaffolds. VWF protein expressions were also
      higher in cells from the pressed scaffold. Real-time PCR showed correlated
      changes too. In addition, the pressed scaffold with EPCs showed the smallest
      torque value among all scaffolds (P<0.01). CONCLUSION: Pressed ECM-like scaffold
      promoted the survival condition of EPC. It may be used to promote
      endothelialization within the next generation of vascular grafts in vivo.

PMID- 19592036
TI  - Commentary.

PMID- 19592037
TI  - Dynamic retention suture closure: modified Bogota bag approach.
AB  - BACKGROUND: Management of patients with abdominal compartment syndrome requires
      abdominal decompression and the use of the open abdomen technique. Various
      options exist for the management of the open abdomen including expensive,
      commercially available devices to aid in the gradual closure of the abdominal
      wall. A previously described temporary closure technique using dynamic retention
      sutures was modified and used in eleven trauma injured patients at the Puerto
      Rico Trauma Center. METHODS: Retrospective case series of 11 trauma patients,
      seven blunt and four penetrating, treated at the Puerto Rico Trauma Center with
      the modified Bogota bag (MBB) approach from October 2005 to November 2006.
      RESULTS: The MBB approach was applied in 11 out of 43 trauma patients (26%) who
      had undergone a Bogota bag closure during an initial damage control surgery.
      Patients' average age was 27.5 (2-65) y old, including 8 males and 3 females,
      with an injury severity score (ISS) of 23.3 (9-38). The MBB placement allowed
      serial approximation in the Trauma ICU with subsequent delayed primary abdominal
      closure. The procedure was used for an average of 7.3 (4-12) d. Abdominal closure
      was achieved in 10 out of 11 patients (91%). CONCLUSIONS: The MBB technique has
      preliminarily proven to be effective, allowing delayed primary closure in 91% of
      the cases. The MBB approach represents an inexpensive and useful alternative in
      the management of the open abdomen.

PMID- 19592038
TI  - In vitro S. epidermidis and S. aureus adherence to composite and lightweight
      polypropylene grafts.
AB  - BACKGROUND: Despite the significant risk of infection, prosthetic graft materials
      have become indispensable for incisional hernia repair. Composite and lightweight
      grafts have been developed to overcome adhesion and rigidity. The aim of this
      study was to evaluate in vitro S. epidermidis and S. aureus adherence to these
      new generation grafts, which have modified composition and textile properties.
      MATERIALS AND METHODS: In this experimental study, sterile samples of
      multifilament polypropylene, multifilament lightweight composite, monofilament
      composite, and monofilament polypropylene grafts were incubated with slime
      positive S. epidermidis and S. aureus strains for 24 h. The grafts were washed
      and vortexed in saline. The saline was passaged to blood agar and incubated for
      24 h. The colonies were counted. Naive and incubated graft materials were
      examined by scanning electron microscopy to reveal both textile properties and
      biofilm formation. Physicochemical properties were evaluated. Wilcoxon signed
      ranks test and Friedman test were used for statistical analysis. RESULTS: S.
      epidermidis showed a significantly decreased adherence to monofilament
      polypropylene graft, and increased adherence to multifilament polypropylene graft
      (P<0.05). S. aureus showed a significant affinity for monofilament composite
      graft (P<0.05). SEM studies showed that biofilm formation was present on
      multifilament polypropylene graft. CONCLUSIONS: Both S. epidermidis and S. aureus
      had significantly less adherence to multifilament lightweight composite than
      multifilament polypropylene graft. S. epidermidis showed a greater affinity to
      monofilament composite graft compared with monofilament polypropylene graft.
      Overall S. epidermidis adherence for multifilament lightweight composite and
      monofilament composite was less than multifilament polypropylene and higher than
      monofilament polypropylene. S. epidermidis and S. aureus showed different
      adherence for each graft. Changes in material composition and textile properties
      may well influence bacterial adherence.

PMID- 19592039
TI  - Deficiency, intake and the dietary requirement for copper.

PMID- 19592040
TI  - Leukoencephalopathy in adults: is it adrenoleukodystrophy? A case report and
      molecular analysis.
AB  - Adult onset cerebral X-ALD (AOCALD) is a rare disease, but should be considered
      an important differential diagnosis in adults presenting with leukencephalopathy.
      We here report the case of a 40-year-old man with a history of progressive
      cognitive decline who presented with a first-time seizure. Initial workup
      included magnetic resonance imaging (MRI) of the brain which showed extensive
      frontotemporal leukoencephalopathy. A subsequent brain biopsy showed
      demyelination and perivascular macrophages. Further workup included serum very
      long chain fatty acid concentration (VLCFA), which was found to be elevated. An
      MRI of the total spine showed diffuse atrophy, but no intrinsic cord signal
      changes, and the diagnosis of AOCALD was established. Genomic sequencing revealed
      a nonsense mutation in exon 8 (2188G-->A, W601X), to our knowledge not reported
      in context with AOCALD. A family pedigree was obtained, and other family members
      at risk were identified and underwent genetic counseling. In conclusion, AOCALD
      is an important differential diagnosis in adults presenting with cognitive
      decline. While treatment for affected patients is often supportive only,
      molecular diagnosis serves as a basis for genetic counseling, identification of
      relatives at risk and timely referral to a treatment program.

PMID- 19592041
TI  - Continued validation of the Symptom Inventory in multiple sclerosis.
AB  - OBJECTIVE: This study examined the construct, discriminant, and incremental
      validity of scores from the short (SI-S) and long (SI-L) forms of the Symptom
      Inventory in persons with MS. METHODS: The sample included 133 individuals with
      MS who completed the SI-L, Performance Scales (PS), EDSS, Multiple Sclerosis
      Walking Scale-12 (MSWS-12), Multiple Sclerosis Impact Scale-29 (MSIS-29), and
      Godin Leisure-Time Exercise Questionnaire (GLTEQ) and then wore an accelerometer
      for 7days. The data were analyzed using SPSS, version 16.0. RESULTS: There were
      large correlations between SI-S and SI-L total and subscale scores and between SI
      S, SI-L, and PS total scores. The correlations were similar in magnitude between
      SI-S, SI-L, and PS scores with EDSS and MSIS-29 scores, but not with MSWS-12,
      accelerometer, and GLTEQ scores. Discriminant function analysis indicated that SI
      S scores better differentiated groups with minimal, moderate, and severe
      disability than did SI-L and PS scores. Regression analysis indicated that SI-S
      and SI-L scores explained incrementally more variance in EDSS, MSWS-12, and MSIS
      29 scores after accounting for PS scores alone. CONCLUSION: Such findings provide
      additional support for the validity of both SI-S and SI-L scores in individuals
      with MS and support the adoption of either the SI-S or SI-L by clinical MS
      researchers.

PMID- 19592043
TI  - Immunohistochemical studies of vascular endothelial growth factor in skin of
      patients with amyotrophic lateral sclerosis.
AB  - Vascular endothelial growth factor (VEGF) is a disulfide-linked dimeric
      glycoprotein that enhances vascular permeability, induces chemotaxis and
      activation of monocytes/macrophages, and promotes growth of vascular endothelial
      cells. Furthermore, VEGF is a multifunctional cytokine, which influences neural
      cells directly, enhancing neuronal survival, axonal outgrowth, and Schwann cell
      proliferation. So far studies of the skin of amyotrophic lateral sclerosis (ALS)
      have shown unique pathological and biochemical abnormalities in collagen, elastic
      fibers, and the ground substance. However, the expression of VEGF in ALS skin has
      not previously been studied. We made a quantitative immunohistochemical study of
      the expression of VEGF in the skin from 15 patients with ALS and 15 control
      subjects. VEGF immunoreactivity was markedly positive in the epidermis and
      moderately positive in some dermal blood vessels and glands in ALS patients.
      These findings became more conspicuous as ALS progressed. The optical densities
      for VEGF immunoreactivity of the epidermis in ALS patients were significantly
      higher (p<0.001) than in control subjects. In addition, there was an appreciable
      positive correlation (r=0.85, p<0.001) in ALS patients between the densities for
      VEGF immunoreactivity and duration of illness, but there was no such correlation
      in control subjects. These data suggest that changes of VEGF in ALS skin are
      likely to be related to the disease process and that metabolic alterations of
      VEGF may take place in the skin of patients with ALS.

PMID- 19592044
TI  - [Quality of life in adolescent survivors of childhood cancer].
AB  - BACKGROUND AND OBJECTIVE: To assess health-related quality of life of adolescent
      survivors of childhood cancer, compared to adolescent's health-related quality of
      life who had no history of cancer. PATIENTS AND METHOD: A total of 372
      adolescents aged between 14 and 19 years, 34 cancer survivors and a comparison
      group of 338 peers without a history of cancer, were assessed. All of them filled
      in the SF-12v(2) in a cross-sectional study. RESULTS: Survivors revealed
      significantly higher mean values compared to the normative group for the Mental
      Component Scale (MCS) from the SF-12v(2) (52,60 vs. 47,85; p=0,004; IC 95%, -7,9-
      1,6). No significant differences between groups were found for the Physical
      Component Scale (PCS), even though adolescent survivors of childhood cancer
      showed higher mean scores (54,03 vs. 52,72). CONCLUSIONS: Adolescent cancer
      survivors showed a satisfactory quality of life (mean scores around the normative
      values), and, specifically, they reported greater perception of psychological
      wellbeing compared to peers.

PMID- 19592045
TI  - [Frailty detection and prevention: a new challenge in elderly for dependence
      prevention].

PMID- 19592046
TI  - [Diagnostic lessons of recurrence pattern after transient ischemic attacks].
AB  - BACKGROUND AND OBJECTIVE: Early stroke recurrence risk alter a transient ischemic
      attack (TIA) is high. We studied the diagnostic implications of the recurrence
      pattern after TIA. METHODS: 210 consecutive TIA patients were studied.
      Ultrasonographic (US), neuroimaging and cardiologic data were collected. RESULTS:
      At 90 day follow-up, 14 patients (6.7%; 95% CI: 3.3-10.1) among 209 suffered an
      ischemic infarction (II), 9 (4.3%; 1.5-7.1) a TIA and 6 (2.9%; 0.6-5.1) a cardiac
      ischemic event. Moreover, 13 patients (6.2%; 2.8-9.6) among 210 with a seven-day
      follow-up had an II. Multivariate analyses only identified the presence of
      intracranial stenoses (HR, 23.29; 95% CI, 3.49 to 23.57; p<0.018) as independent
      predictors of stroke within the first 7 days, and large-artery occlusive disease
      (HR, 9.07; CI, 3.49 to 23.57; p<0.001) as a predictor of stroke recurrence at 90
      day follow-up. A new diagnosis of atrial fibrillation was observed in 21 subjects
      (10.0%), and it was documented in the baseline ECG in 62% cases. Acute diffusion
      abnormalities were identified in 81 (44,5%) of 182 patients, and chronic ischemic
      lesions were observed in 110 (60.4%) on MRI vs 56 (26.7%) among 210 on CT scan.
      CONCLUSION: Due to very early recurrence, the routine use of ultrasonography
      within the first hours after an index TIA will be useful to identify those
      patients at high risk. The prognostic usefulness of diffusion-weighted studies
      will be only achieved if it is performed early. Routine noninvasive cardiac
      rhythm monitoring has a low detection rate.

PMID- 19592047
TI  - [New understanding of breast cancer].

PMID- 19592049
TI  - The influence of sex, body composition, and nonesterified fatty acids on serum
      adipokine concentrations.
AB  - Serum adiponectin concentrations are higher in women than men. The sexual
      dimorphism for adiponectin has been attributed to the direct effects of
      testosterone on adipose tissue adiponectin secretion. However, serum testosterone
      and adiponectin concentrations are generally lower in obese men than lean men,
      suggesting that sex steroids may not be the only factor that contributes to sex
      differences in serum adiponectin. The primary objective of this study was to
      examine the influence of sex, body composition, and nonesterified fatty acids
      (NEFAs) on serum adiponectin concentrations. Women and men between the ages of 18
      and 35 years were consecutively accrued into the study. Sixty-one participants
      were partitioned into normal-weight (15 female and 16 male) or obese (14 female
      and 16 male) groups. Blood samples were obtained after a 12-hour fast.
      Differences between groups were determined by analysis of variance with Tukey
      Kramer post hoc testing. Serum adiponectin was 26% higher in women compared with
      men. Body mass index was associated with total serum adiponectin in men (r = 
      0.63, P < .05) but not women. Adiponectin was correlated with the homeostasis
      model assessment index in women (r = -0.56, P < .05) and men (r = -0.58, P < .05)
      and with NEFAs (r = -0.68, P < .05) in men only. After partitioning men and women
      into normal-weight and obese groups, serum adiponectin was lower and NEFAs were
      higher in obese men only. Homeostasis model assessment was similar between obese
      women and men despite higher NEFAs in the obese men. Leptin and plasminogen
      activator inhibitor-1 were higher in obese participants but were not associated
      with serum NEFAs. These results suggest that serum NEFAs may reduce adiponectin
      concentrations independent of their effects on insulin sensitivity in obese young
      men.

PMID- 19592048
TI  - Fasting and postprandial apolipoprotein B-48 levels in healthy, obese, and
      hyperlipidemic subjects.
AB  - Apolipoprotein (apo) B-48 is the only specific marker of intestinal lipoproteins.
      We evaluated a novel enzyme-linked immunosorbent assay (ELISA) standardized with
      recombinant apo B-48 to measure apo B-48 in plasma and triglyceride-rich
      lipoproteins (TRLs, density <1.006 g/mL). Coefficients of variation were less
      than 2.5%. Assay values correlated well (r = 0.82, P < .001) with values obtained
      by gel scanning of TRLs (n = 75 samples); however, the gel scanning method
      yielded values that were about 50% lower than ELISA values. About 60% to 70% of
      apo B-48 was found in TRLs. In 12 healthy subjects, median fasting plasma apo B
      48 levels were 0.51 mg/dL and were increased by 121% to 147% in the fed state. In
      63 obese subjects, median fasting apo B-48 values were 0.82 mg/dL; and feeding
      resulted in almost no change in total cholesterol, non-high-density lipoprotein
      cholesterol, or total apo B values, whereas triglyceride, remnant lipoprotein
      cholesterol, and apo B-48 levels were significantly higher (P < .05; by +73%,
      +58%, and +106%), and direct low-density lipoprotein cholesterol and direct high
      density lipoprotein cholesterol were significantly lower (P < .001, by -13% and 
      20%) than fasting values. Relative to controls, 270 hyperlipidemic subjects had
      significantly higher (P < .001, +115%) fasting total apo B and higher apo B-48
      values (P = .06, +37%). Our data indicate that the apo B-48 ELISA tested provides
      highly reproducible results and is excellent for research studies. Median apo B
      48 values in healthy subjects are about 0.5 mg/dL and increase more than 100% in
      the fed state. Elevated levels are observed in obese and hyperlipidemic subjects.

PMID- 19592050
TI  - Variants in the insulin-degrading enzyme gene are associated with metabolic
      syndrome in Chinese elders.
AB  - Metabolic syndrome (MetS) is a cluster of metabolic abnormalities sharing
      potential common underlying mechanisms. Insulin-degrading enzyme (IDE) plays a
      primary role in insulin degradation and cellular insulin processing and therefore
      affects glucose and lipid metabolism. Genetic association studies have been
      focused on the relationship between the IDE gene and the development of MetS. To
      identify specific genetic risks for MetS associated with IDE gene, a case-control
      association study was performed on 563 Chinese elders in Shanghai, China. Cases
      were those with MetS (n = 241), and controls were those without MetS (n = 219).
      Five unrelated genetic markers (single nucleotide polymorphisms) at the IDE gene
      were used for association analyses. The single-locus association analysis
      revealed that the A/T allele of rs11187033 was associated with MetS (odds ratio =
      0.698; 95% confidence interval, 0.526-0.928; P = .013). Patients with MetS had
      more haplotype G-T-Ts than controls (P = .008). None of the other 4 single
      nucleotide polymorphisms was significantly associated with MetS. This result
      suggests that the rs11187033 at IDE gene might contribute to MetS susceptibility
      in Chinese elders.

PMID- 19592051
TI  - Serum high-molecular weight adiponectin decreases abruptly after an oral glucose
      load in subjects with normal glucose tolerance or impaired fasting glucose, but
      not those with impaired glucose tolerance or diabetes mellitus.
AB  - Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a
      high-molecular weight (HMW) form. We investigated whether circulating HMW
      adiponectin levels were altered by oral glucose or fat ingestion. Forty male
      subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy
      subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and
      total adiponectin were measured during the OGTT and the fat loading test. The fat
      loading test was performed for at least 8 hours. Among the 40 male subjects, 11
      had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had
      impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects,
      the serum total adiponectin level did not change significantly, whereas serum HMW
      adiponectin decreased significantly after a glucose load and reached 92.2% of the
      basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin
      ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at
      120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120
      minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal
      level in subjects with NGT or IFG, respectively (both P < .01). In subjects with
      impaired glucose tolerance or DM, however, serum HMW adiponectin did not change.
      The area under the curve for insulin at 30 minutes after a glucose load during
      the OGTT was significantly larger in subjects with NGT or IFG than in those with
      DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30))
      was significantly higher in subjects with NGT or IFG than in those with DM (P <
      .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes
      correlated negatively with those in serum insulin (r = -0.468, P = .0023), but
      not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other
      hand, serum triglycerides increased significantly after an oral fat load in 11
      healthy subjects; but neither serum total nor HMW adiponectin changed. In
      conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly
      after glucose loading in subjects with NGT or IFG; and the decrease of HMW
      adiponectin may be associated with an increase of serum insulin at 30 minutes.

PMID- 19592052
TI  - Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a
      patient with lecithin-cholesterol acyltransferase deficiency: a clinicopathologic
      correlation.
AB  - A 31-year-old man with no significant medical history presented with a 5-day
      history of progressive left upper quadrant abdominal pain. Physical examination
      revealed a tender guarded abdomen, no icterus, and bilateral corneal "arcus
      senilis"-like changes. Laboratory workup showed a mild normocytic, normochromic
      anemia; and target cells were seen in the peripheral blood smear. Serum was
      turbid; and the lipid profile showed elevated total cholesterol, low high-density
      lipoprotein cholesterol, and elevated triglycerides. Urinalysis revealed
      nephrotic range proteinuria with microhematuria. An abdominal computed
      tomographic scan demonstrated a homogeneously enlarged spleen. The patient was
      discharged after symptomatic treatment to be followed as an ambulatory patient.
      Several days later, he returned with severe left upper quadrant pain and was
      admitted to the surgical service for further evaluation. A splenectomy was
      performed for a suspected splenic lymphoma. Upon gross examination, spleen was
      moderately enlarged, weighing 780 g. Sectioning revealed a beefy red cut surface
      without gross lesions. Wright-Giemsa-stained touch imprints showed many sea-blue
      histiocytes. A renal biopsy was also performed, demonstrating focal segmental
      glomerular sclerosis and mesangial expansion with extramembranous and
      intramembranous deposition of lipids. In the absence of hematologic malignancy
      and in light of the abnormal lipid profile, a disorder of lipid metabolism was
      suspected. Histologic and ultrastructural findings in the kidney and spleen
      raised the likelihood of lecithin-cholesterol acyltransferase (LCAT) deficiency,
      which was confirmed by the markedly decreased serum LCAT activity and serum LCAT
      mass. We describe a case with the triad of splenomegaly with sea-blue
      histiocytes, nephropathy, and dyslipidemia in a patient with LCAT deficiency.

PMID- 19592053
TI  - Altered metabolism of copper, zinc, and magnesium is associated with increased
      levels of glycated hemoglobin in patients with diabetes mellitus.
AB  - Diabetes mellitus (DM) is associated with the alterations in the metabolism of
      copper (Cu), zinc (Zn), and magnesium (Mg). The aim of the present study was to
      investigate plasma levels of these elements in patients with DM and in healthy
      subjects. Association between glycated hemoglobin and levels of metals was also
      evaluated. We studied 36 subjects with DM (type 1, 11; type 2, 25) and 34 healthy
      subjects matched for age, sex, and duration of diabetes. Plasma concentrations of
      Cu, Zn, and Mg were measured by atomic absorption spectrometry. An imbalance in
      the levels of studied metals was observed in both type 1 and type 2 DM. We found
      higher levels of Cu (P < .001) and Cu/Zn ratio (P < .0001) and decreased levels
      of Zn (P < .01) and Mg (P < .0001) in patients with DM when compared with
      controls. Negative correlation between Cu and Zn (r = -0.626, P < .0001) was
      found in patients with DM. Glycated hemoglobin levels were positively correlated
      with Cu (r = 0.709, P < .001) and Cu/Zn ratio (r = 0.777, P < .001) and inversely
      correlated with Zn (r = - 0.684, P < .001) and Mg (r = -0.646, P < .001). In
      conclusion, patients with DM had altered metabolism of Cu, Zn, and Mg; and this
      may be related to increased values of glycated hemoglobin. We concluded that
      impaired metabolism of these elements may contribute to the progression of DM and
      diabetic complications.

PMID- 19592054
TI  - Oral L-arginine supplementation improves endothelial function and ameliorates
      insulin sensitivity and inflammation in cardiopathic nondiabetic patients after
      an aortocoronary bypass.
AB  - It is known that L-arginine treatment can ameliorate endothelial dysfunction and
      insulin sensitivity in type 2 diabetes mellitus patients, but little is known on
      L-arginine effects on these variables in nondiabetic patients with stable
      cardiovascular disease (coronary artery disease). We evaluated the effects of
      long-term oral L-arginine treatment on endothelial dysfunction, inflammation,
      adipokine levels, glucose tolerance, and insulin sensitivity in these patients.
      Sixty-four patients with cardiovascular disease previously submitted to an
      aortocoronary bypass and not known for type 2 diabetes mellitus had an oral
      glucose load to define their glucose tolerance. Thirty-two patients with
      nondiabetic response were eligible to receive, in a double-blind randomized
      parallel order, L-arginine (6.4 g/d) or placebo for 6 months. An evaluation of
      insulin sensitivity index during the oral glucose load, markers of systemic
      nitric oxide bioavailability and inflammation, and blood flow was performed
      before and at the end of the treatment in both groups. Compared with placebo, L
      arginine decreased asymmetric dimethylarginine levels (P < .01), indices of
      endothelial dysfunction, and increased cyclic guanosine monophosphate (P < .01),
      L-arginine to asymmetric dimethylarginine ratio (P < .0001), and reactive
      hyperemia (P < .05). Finally, L-arginine increased insulin sensitivity index (P <
      .05) and adiponectin (P < .01) and decreased interleukin-6 and monocyte
      chemoattractant protein-1 levels. In conclusion, insulin resistance, endothelial
      dysfunction, and inflammation are important cardiovascular risk factors in
      coronary artery disease patients; and L-arginine seems to have anti-inflammatory
      and metabolic advantages in these patients.

PMID- 19592055
TI  - Weight reduction can decrease circulating soluble lectin-like oxidized low
      density lipoprotein receptor-1 levels in overweight middle-aged men.
AB  - Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX
      1) has been reported to be associated with acute coronary syndrome, but its
      association with obesity has not been elucidated. In this study, we examined
      whether weight reduction would reduce the serum levels of sLOX-1 in a 12-week
      weight reduction intervention. Thirty-eight overweight middle-aged men were
      enrolled in the study, and 32 completed the intervention. The serum level of sLOX
      1 was measured using a chemiluminescent enzyme-linked immunoassay. After the
      intervention program, body weight and the serum level of sLOX-1 decreased
      significantly (-7.5% +/- 4.8% and -72.1% +/- 35.9%, respectively). Changes in
      serum levels of sLOX-1 were positively correlated with changes in body weight (r
      = 0.54, P = .003), body mass index (r = 0.57, P = .001), body fat mass (r = 0.57,
      P = .002), total cholesterol (r = 0.41, P = .03), subcutaneous fat area (r =
      0.50, P = .007), high-sensitivity C-reactive protein (r = 0.56, P = .002), leptin
      (r = 0.47, P = .01), and tumor necrosis factor-alpha (r = 0.32, P = .09); but no
      correlations were observed with fasting glycemic-related factors (blood glucose,
      hemoglobin A(1c), and insulin). Changes in body mass index and high-sensitivity C
      reactive protein were selected as significant predictors of sLOX-1 changes by
      multiple regression analyses. These results suggest that LOX-1 induction may be
      related to adipocyte metabolism, inflammation, and immune response associated
      with obesity.

PMID- 19592056
TI  - [Severe orthostatic hypotension and intramedullary tumor: a case report and
      review of the literature].
AB  - A 55-year-old woman presented with bilateral neuropathic pain of the upper limbs,
      motor palsy of the right arm, urinary dysfunction, and postural dizziness. MRI
      showed an intramedullary cervical tumor with a solid portion extended from C1 to
      C3 surrounded by a cystic portion. A macroscopic complete resection was performed
      and histological examination confirmed the diagnosis of ependymoma.
      Postoperatively, the patient's neuropathic pain and postural dizziness worsened,
      with syncopal attack while upright because of severe orthostatic hypotension
      (OH). On physical examination, her supine systolic blood pressure was 130 mmHg
      and fell to 80 mmHg while sitting with no change in heart rate. We found motor
      palsy of the left arm, bilateral ataxia, and urinary retention. Three months
      later, the patient was still bedridden, notably because of the OH. After 6
      months, with the association of preventative measures of OH and high doses of a
      direct alpha1-adrenoreceptor agonist, a vasoconstricting agent, the patient
      recovered an independent gait permitting her to walk unassisted. The main causes
      of OH include medication, nonneurogenic causes such as cardiac insufficiency, and
      central or peripheral neurogenic causes such as diabetic insufficiency. Brainstem
      tumors are known to provide severe OH but this symptom has been seldom described
      in a purely spinal cord lesion. We report an interesting case of severe OH that
      had complicated the surgical treatment of a high cervical spinal cord ependymoma
      and we review the literature.

PMID- 19592057
TI  - [Chondrosarcomas of skull base treatment].
AB  - BACKGROUND AND PURPOSE: Skull base chondrosarcomas are rare. Gross total removal
      is the treatment of choice, but can be difficult depending on the closeness of
      noble structures. Proton beam therapy can be associated in most cases. METHODS:
      Retrospective study of five cases treated in 13 years and study of the
      literature. RESULTS: Median age of patients was 34 years [28-46]. Cranial nerve
      palsy was the common clinical presentation. Tumor location was variable but
      always off midline. Treatment was surgical in all patients with a maximal
      resection and proton beam therapy associated for two cases. Surgical
      complications were rare with cranial nerve palsy as the main side effect.
      Outcomes were good with a median follow-up of 12.4 years [4.3-16.2]. DISCUSSION:
      The review of the literature showed that chondrosarcomas of skull base are rare.
      The best outcome is achieved with total surgical resection. Medical imaging can
      only give clues to the diagnosis. Pathology is required to obtain a precise
      immunohistochemistry diagnosis. Multidisciplinary treatment using proton beam
      therapy and surgical removal enables a good local control (90-100%) at 5 years
      with good quality-of-life. It is difficult to determine how many cases have been
      published (around 220 cases in the literature) since many surgical or
      radiotherapy series included the same patients.

PMID- 19592058
TI  - [Bilateral intracerebral angioplasty in a patient with stroke caused by giant
      cell arteritis].
AB  - INTRODUCTION: Giant cell arteritis is the most frequent vasculitis and can cause
      stroke in about 4% of the patients. The mechanism is often hemodynamic in
      relation with an arterial stenosis or occlusion. Optimal treatment remains to be
      defined. Outcome is often poor. CASE REPORT: We report the case of a 78-year-old
      patient, with giant cell arteritis who developed neurological deterioration after
      the onset of the corticotherapy. Brain MRI revealed bilateral stroke caused by
      multiple preocclusive internal carotid stenosis. The patient was treated
      successfully with angioplasty and stenting. CONCLUSION: Endovascular treatment
      could constitute an interesting alternative for patients with giant cell
      arteritis associated with neurological deterioration after a first episode of
      stroke because of hemodynamic instability or at stroke recurrence. For these
      patients, the usual medical treatment appears to be insufficient.

PMID- 19592059
TI  - [Trigeminal neuralgia revealing neurosyphilis].

PMID- 19592060
TI  - [Multiple acyl-CoA dehydrogenase deficiency (MADD): a curable cause of genetic
      muscular lipidosis].
AB  - INTRODUCTION: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare genetic
      disease involving fatty acid oxidation. It is due to the deficiency of one of the
      two electron transporters: electron transfer flavoprotein (ETF) or electron
      transfer flavoprotein ubiquinone oxydoreductase (ETF-QO). Symptoms begin more
      often in childhood or in young adulthood with a multisystemic disease with
      encephalopathy or muscular weakness. CASE REPORTS: We report here two adult cases
      with ETF-QO deficiency, confirmed by mutation analysis (ETFDH gene), revealed by
      a muscular weakness associated with muscle lipidosis. One of our patients
      presented an acute encephalopathy with vomiting ten years before the onset of
      muscular symptoms. The second patient exhibited a slowly progressive pelvic
      girdle muscle weakness. Diagnosis was established by characteristic abnormalities
      of acylcarnitine profile by tandem mass spectrometry. For both patients, a
      dramatic clinical improvement was observed under treatment with riboflavine and L
      carnitine. CONCLUSION: Since it is a treatable disorder, this diagnosis must be
      considered by performing an acylcarnitine profile in all patients presenting with
      an unexplained muscular weakness.

PMID- 19592061
TI  - Genomes of "phiKMV-like viruses" of Pseudomonas aeruginosa contain localized
      single-strand interruptions.
AB  - The "phiKMV-like viruses" comprise an important genus of T7 related phages
      infecting Pseudomonas aeruginosa. The genomes of these bacteriophages have
      localized single-strand interruptions (nicks), a distinguishing genomic trait
      previously thought to be unique for T5 related coliphages. Analysis of this
      feature in the newly sequenced phage phikF77 shows all four nicks to be localized
      on the non-coding DNA strand. They are present with high frequencies within the
      phage population and are introduced into the phage DNA at late stages of the
      lytic cycle. The general consensus sequence in the nicks (5'-CGACxxxxxCCTAoh
      pCTCCGG-3') was shown to be common among all phiKMV-related phages.

PMID- 19592064
TI  - The origin of Al(OH)(3)-rich and Al(13)-aggregate flocs composition in PACl
      coagulation.
AB  - The composition of hydrolyzed Al species is essential for the understanding of
      coagulation with Al-based coagulants. Surface characteristics of flocs formed by
      coagulation with two distinct polyaluminum chloride (PACl) coagulants were
      identified. One commercial coagulant (PACl-C) with voluminous monomeric Al and
      colloidal Al(OH)(3) and a custom-made PACl (PACl-Al(13)) containing high Al(13)
      content were applied to destabilize kaolin particles. The flocs formed by PACl-C
      and PACl-Al(13) at neutral and alkaline pH ranges, respectively, were observed by
      FE-SEM and HR-TEM. In addition, the Al composition of these flocs was
      characterized by XPS and HR-XRD, and the imaging of Al(OH)(3) precipitates and
      Al(13) aggregates were conducted by SEM as well as tapping mode AFM in liquid
      system. The observations of flocs indicate that the morphology of Al(OH)(3)-rich
      flocs are fluffy and porous around the edge of flocs, while the Al(13)-aggregate
      flocs have a glossy contour and irregular structure. Both Al(OH)(3)-rich and
      Al(13)-aggregate flocs do not possess well-formed crystalline structure except
      for the Al(13)-like crystal exists in the Al(13)-aggregate flocs. Among Al(OH)(3)
      precipitates, colloidal Al(OH)(3) is micro-scale in size, while amorphous
      Al(OH)(3) is nano-scale. During the formation of Al(13) aggregates, some coiled
      and clustered Al(13) aggregates with smoother surface were observed. The XPS
      study on floc surface showed that tetrahedral (Al(IV)) /octahedral (Al(VI)) Al
      ratio on the surfaces of PACl-C and PACl-Al(13) flocs is 1:1.6 and 1:9.9,
      respectively. Of the in situ formed Al(13), almost half of Al-hydroxide
      precipitates on the surface of Al(OH)(3)-rich flocs possess the Al(IV) center. It
      also found that the irregularly aggregated Al(13) with a similar Al(13)
      crystalline structure subsists on the surface of Al(13)-aggregate flocs.

PMID- 19592062
TI  - The zinc finger DNA-binding domain of K-RBP plays an important role in regulating
      Kaposi's sarcoma-associated herpesvirus RTA-mediated gene expression.
AB  - K-RBP is a KRAB-containing zinc finger protein with multiple zinc finger motifs
      and represses Kaposi's sarcoma-associated herpesvirus (KSHV) transactivator RTA
      mediated transactivation of several viral lytic gene promoters, including the
      ORF57 promoter. Whether K-RBP binds DNA through its zinc fingers and the role of
      zinc finger domain in repressing gene expression are unclear. Here we report that
      K-RBP binds DNA through its zinc finger domain and the target DNA sequences
      contain high GC content. Furthermore, K-RBP binds to KSHV ORF57 promoter, which
      contains a GC-rich motif. K-RBP suppresses the basal ORF57 promoter activity as
      well as RTA-mediated activation. The zinc finger domain of K-RBP is sufficient
      for the suppression of ORF57 promoter activation mediated by the viral
      transactivator RTA. Finally, we show that K-RBP inhibits RTA binding to ORF57
      promoter. These findings suggest that the DNA-binding activity of K-RBP plays an
      important role in repressing viral promoter activity.

PMID- 19592065
TI  - A QSAR-like analysis of the adsorption of endocrine disrupting compounds,
      pharmaceuticals, and personal care products on modified activated carbons.
AB  - Rapid small-scale column tests (RSSCTs) examined the removal of 29 endocrine
      disrupting compounds (EDCs) and pharmaceutical/personal care products (PPCPs).
      The RSSCTs employed three lignite variants: HYDRODARCO 4000 (HD4000), steam
      modified HD4000, and methane/steam-modified HD4000. RSSCTs used native Lake Mead,
      NV water spiked with 100-200 ppt each of 29 EDCs/PPCPs. For the steam and
      methane/steam variants, breakthrough occurred at 14,000-92,000 bed volumes (BV);
      and this was 3-4 times more bed volumes than for HD4000. Most EDC/PPCP bed life
      data were describable by a normalized quantitative structure-activity
      relationship (i.e. QSAR-like model) of the form: where TPV is the pore volume,
      rho(mc) is the apparent density, CV is the molecular volume, C(o) is the
      concentration, (8)chi(p) depicts the molecule's compactness, and FOSA is the
      molecule's hydrophobic surface area.

PMID- 19592063
TI  - Receptor for advanced glycation end products is detrimental during influenza A
      virus pneumonia.
AB  - Pneumonia caused by influenza A virus (IAV) can have devastating effects,
      resulting in respiratory failure and death. The idea that a new influenza
      pandemic might occur in the near future has triggered renewed interests in IAV
      infection. The receptor for advanced glycation end products (RAGE) is expressed
      on different cell types and plays a key role in diverse inflammatory processes.
      We here investigated the role of RAGE in the host response to IAV pneumonia using
      wild-type (wt) and RAGE deficient ((-/-)) mice. Whereas strong RAGE was
      constitutively expressed in the lungs of uninfected wt mice, in particular on
      endothelium, IAV pneumonia was associated with enhanced expression on endothelium
      and de novo expression on bronchial epithelium. Additionally, the high-affinity
      RAGE ligand high mobility group box 1 was upregulated during IAV pneumonia. RAGE(
      /-) mice were relatively protected from IAV induced mortality and showed an
      improved viral clearance and enhanced cellular T cell response and activation of
      neutrophils. These data suggest that RAGE is detrimental during IAV pneumonia.

PMID- 19592066
TI  - Conventional and (eco) toxicological assessment of batch partial ozone oxidation
      and subsequent biological treatment of a tank truck cleaning generated
      concentrate.
AB  - This paper compares the treatment efficiencies of direct (pH 7.5) and advanced
      (pH 11.5) partial ozonation followed by biodegradation for the treatment of tank
      cleaning wastewater concentrate. Both S(COD) and toxicity removal efficiencies
      are examined and direct ozonation is found to perform better in combined toxicity
      and S(COD) removal. Optimal process performance, i.e. the minimal ozone dosage
      resulting in a maximal removal of S(COD) and toxicity in the final effluent, is
      reached upon reaction of 500 mg O(3)/l for both ozonation processes. This ozone
      dosage results in 60% S(COD) reduction for direct ozonation and 64% S(COD)
      reduction for advanced ozonation. A 79% toxicity reduction was achieved using
      direct ozonation compared to 53% toxicity reduction for advanced ozonation as
      measured with the standard Pseudokirchneriella subcapitata algal 72h growth
      inhibition test. Short-term methods for biodegradability (respirometry) and
      toxicity (30 min Vibrio fisheri luminescence inhibition) estimation are evaluated
      in view of process control. The maximal specific oxygen uptake rate of an
      activated sludge culture (respirometry) is found to relate to the 5-day
      biochemical oxygen demand (S(BOD,5)) but less to the actual S(COD) removal during
      biodegradation. The 30 min Vibrio fisheri luminescence inhibition test is found
      to be a good short-term estimator for relative changes in toxicity when compared
      to the standard P. subcapitata algal 72h growth inhibition test. The 500 mg
      O(3)/l optimal ozone dosage, as determined from P. subcapitata algal 72h growth
      inhibition and S(COD) removal, could be retrieved using short-term methods.

PMID- 19592067
TI  - Photolytic removal and mineralisation of 2-halogenated pyridines.
AB  - The photolytic destruction and mineralisation of 2-halogenated pyridines (2
      HalPYs) was studied in a range of conditions by means of ultraviolet irradiation
      at 254 nm. In all cases pseudo-first order kinetics satisfactorily describe the
      degradation process. Key decomposition products were identified and primary
      reaction pathways are proposed. 2-HalPYs were rapidly dehalogenated with a
      subsequent sharp pH drop. Complete Total Organic Carbon (TOC) removal was
      achieved. Their photolytic removal rate is not affected by pH or aeration. The
      fastest TOC removal was observed in 2-fluoropyridine (2-FPY) photolysis. 2
      Hydroxypyridine (2-HPY) was identified as the primary intermediate formed by
      destruction of 2-chloropyridine (2-CPY), 2-bromopyridine (2-BPY) and 2
      iodopyridine (2-IPY). 2-HPY is further destructed to form Dewar pyridinone. 2-FPY
      only marginally reacted to form 2-HPY. Instead, its major intermediate product is
      Dewar pyridinone. 2-IPY results in a, most likely aliphatic, photostable product,
      the production of which appears to increase at low pH and high 2-HPY
      concentration.

PMID- 19592068
TI  - Cyclophosphamide removal from water by nanofiltration and reverse osmosis
      membrane.
AB  - The rejection of cyclophosphamide (CP) by nanofiltration (NF) and reverse osmosis
      (RO) membranes from ultrapure (Milli-Q) water and membrane bioreactor (MBR)
      effluent was investigated. Lyophilization-extraction and detection methods were
      first developed for CP analysis in different water matrices. Experimental results
      showed that the RO membrane provided excellent rejection (>90%) under all
      operating conditions. Conversely, efficiency of CP rejection by NF membrane was
      poor: in the range of 20-40% from Milli-Q water and around 60% from MBR effluent.
      Trans-membrane pressure, initial CP concentration and ionic strength of the feed
      solution had almost no effect on CP retention by NF. On the other hand, the water
      matrix proved to have a great influence: CP rejection rate by NF was clearly
      enhanced when MBR effluent was used as the background solution. Membrane fouling
      and interactions between the CP and water matrix appeared to contribute to the
      higher rejection of CP.

PMID- 19592069
TI  - The effects of sacral acupuncture on acetic acid-induced bladder irritation in
      conscious rats.
AB  - OBJECTIVES: To investigate the effects of sacral acupuncture on acetic acid
      induced bladder irritation using cystometry in conscious rats, with particular
      focus on effects on afferent fibers of the bladder. METHODS: A total of 40 female
      Sprague-Dawley rats weighing 200-270 g were used. The animals were divided into 5
      groups: (1) rats with bladder overactivity induced by acetic acid, without sacral
      acupuncture stimulation (irritated bladder group); (2) rats treated with sacral
      acupuncture stimulation after induction of bladder overactivity by acetic acid
      (acupuncture stimulation group); (3) rats treated with sacral acupuncture
      stimulation after capsaicin desensitization (capsaicin-desensitized group); (4)
      rats treated with atropine (atropine injection group); and (5) rats treated with
      sacral acupuncture stimulation after nonacetic acid infusion (nonirritated
      bladder group). Cystometry was carried out without anesthesia, and the following
      variables were measured in all animals: intercontraction interval (ICI), basal
      pressure, threshold pressure, and micturition pressure. RESULTS: In the
      acupuncture stimulation group, sacral acupuncture stimulation resulted in a 140.1
      +/- 5.9% increase in ICI after acetic acid-induced irritation to an interval
      similar to baseline (P = .072). A significant difference in the percent of ICI
      increase was observed between the acupuncture stimulation and irritated bladder
      groups (P < .01). In the capsaicin-desensitized groups and acupuncture
      stimulation groups, no significant differences in ICI occurred, before and after
      acupuncture. CONCLUSIONS: Sacral acupuncture could contribute to improve acetic
      acid-induced bladder irritation through inhibition of capsaicin-sensitive C-fiber
      activation.

PMID- 19592070
TI  - Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen
      species production and mitochondrial depolarization.
AB  - OBJECTIVES: To investigate the effects of capsaicin (CAP) on proliferation of
      bladder cancer T24 cells in vitro as well as on xenografts in nude mice in vivo.
      METHODS: T24 cells were assessed for cell viability and apoptosis by 3-(4, 5
      dimethylthiazol-2-yl)-3, 5-diphenyltetrazolium bromide assay and flow cytometry
      analysis after incubation with different concentrations of CAP. To uncover the
      mechanism by which CAP affected the viability of T24 cells, intracellular
      production of reactive oxygen species (ROS) and mitochondrial membrane potential
      were assessed. To study the in vivo effects of CAP, T24 cells were grown as
      xenografts in nude mice and CAP (5 mg/kg by wt) was subcutaneously injected into
      nude mice with bladder tumors. RESULTS: CAP decreased the viability of T24 cells
      in a dose-dependent manner without marked apoptosis. CAP induced ROS production
      and mitochondrial membrane depolarization, thereby inducing cell death, not
      apoptosis, in T24 cells at a concentration of 100 microM or higher. Furthermore,
      these effects of CAP could be reversed by capsazepine, the antagonist of
      transient receptor potential vanilloid type 1 channel. In vivo experiment showed
      that CAP significantly slowed the growth of T24 bladder cancer xenografts as
      measured by size (661.80 +/- 62.03 vs 567.02 +/- 43.94 mm(3); P <.01).
      CONCLUSIONS: CAP mediates cell death in T24 cells through calcium entry-dependent
      ROS production and mitochondrial depolarization, and it may have a role in the
      management of bladder cancer.

PMID- 19592071
TI  - Ganglioneuroblastoma in a patient with crossed testicular ectopia.
AB  - Crossed testicular ectopia is an extremely rare congenital disorder in which both
      testes descend toward the same hemiscrotum. Twenty percent of cases with crossed
      testicular ectopia are accompanied by urogenital anomalies such as hypospadias,
      seminal vesicle cysts, renal anomalies associated with obstruction of the
      ureteropelvic junction, and testicular tumors. In the case reported here, we
      describe a patient with ganglioneuroblastoma and crossed testicular ectopia.

PMID- 19592072
TI  - Age-related Epstein-Barr virus-associated lymphoproliferative disorder presenting
      as renal mass.

PMID- 19592073
TI  - Androgen pattern in patients with type 2 diabetes-associated erectile
      dysfunction: impact of metabolic control.
AB  - OBJECTIVES: To assess the impact of diabetes mellitus (DM) control on androgen
      pattern in men with type 2 DM-associated erectile dysfunction (ED). METHODS: This
      is a prospective office-based study. A total of 159 ED male patients with DM were
      enrolled in this study. Erectile function was assessed using the international
      index of erectile function (IIEF). Diabetes control was instituted using
      lifestyle modification in addition to hypoglycemic agents and/or insulin therapy.
      Regular follow-up visits were scheduled every 4 weeks to adjust the anti-DM
      treatment according to patients' response and tolerance. At baseline, 3- and 6
      month visits, patients were assessed for control of DM, ED severity, and total
      testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), and insulin
      assessment. RESULTS: Of all patients, 25.8%, 6.3%, and 30.2% had low total T, low
      DHEA-S, and hyperinsulinemia, respectively, at baseline visit. There were
      significant increases in the mean total T levels (4.2 +/- 1.9 vs 4.7 +/- 2.1 and
      5.3 +/- 2.2) and significant decreases in insulin level (23.7 +/- 17.4 vs 22.8 +/
      15.3 and 17.8 +/- 13.9) at 3- and 6-month visits, respectively. There were
      significant associations between good control of DM or decreased fasting blood
      sugar and normal levels of total T at 3- and 6-month visits. The prevalence of
      patients with normal testosterone and severe ED was significantly increased at 3-
      and 6-month visits. CONCLUSIONS: The present study clearly demonstrated that
      there were significant associations between control of DM and normal total T
      levels at 3- and 6-month follow-up visits.

PMID- 19592074
TI  - Maternal use of oral contraceptives during early pregnancy and risk of
      hypospadias in male offspring.
AB  - OBJECTIVES: To examine the association between maternal use of oral
      contraceptives in early pregnancy and increased prevalence of hypospadias in male
      offspring. METHODS: We conducted a nationwide population-based case-control study
      using data from nationwide medical databases. Among live male births between
      January 1, 1996, and December 31, 2005, we identified all cases of hypospadias
      recorded anytime postpartum (n = 1683) and randomly selected 10 controls per case
      without such a diagnosis (n = 15 650), matched by year and hospital of birth. We
      used conditional logistic regression to estimate prevalence ratios stratified
      according to time of diagnosis (within 6 months postpartum, >6 months
      postpartum), controlling for potential confounding factors including maternal
      age, birth order, maternal smoking, prescriptions for ovulation-inducing drugs,
      antiepileptics, and antidiabetics, and a maternal diagnosis of pre-eclampsia.
      RESULTS: We included 1683 cases of hypospadias and 15,650 population controls
      during 1996-2005. Among the 1186 boys who had their hypospadias diagnosis
      recorded within 6 months postpartum, 28 (2.4%) had been exposed to oral
      contraceptives between 30 days before conception until the end of the first
      trimester. Among the controls, 307 (2.8%) were similarly exposed, corresponding
      to a prevalence ratio of 0.85 (95% CI: 0.57-1.27) after adjusting for possible
      confounders. For a diagnosis registered >6 months postpartum, the adjusted
      prevalence ratio was 1.12 (95% CI: 0.61-2.06). CONCLUSIONS: Our data do not
      support the hypothesis that maternal use of oral contraceptives around conception
      is associated with an increased prevalence of hypospadias in the offspring.

PMID- 19592075
TI  - Trifecta outcomes after robotic-assisted laparoscopic prostatectomy.
AB  - OBJECTIVE: To evaluate the trifecta outcomes following robotic-assisted
      laparoscopic prostatectomy (RALP) and compare the results applying definitions of
      continence and potency as reported in the literature vs validated questionnaire.
      The trifecta rate of achieving continence, potency, and undetectable prostate
      specific antigen (PSA) following radical prostatectomy has been estimated to be
      approximately 60% at 1-2 years in open radical prostatectomy series. The
      definitions of continence and potency were not standardized, which poses
      difficulty in comparing published results. METHODS: A prospective, institutional
      RALP database was analyzed for preoperatively continent and potent men with >/= 1
      year follow-up after bilateral nerve-sparing surgery. Continence and potency were
      evaluated preoperatively and at 3, 6, 12, and 24 months after surgery by surgeon
      interview (subjective) and using University of California Los-Angeles Prostate
      Cancer Index self-administered questionnaire (objective). Biochemical recurrence
      was defined as a detectable (> 0.05 ng/mL), increasing PSA on 2 consecutive
      tests. RESULTS: Among 1362 consecutive RALPs, 380 patients were preoperatively
      potent and continent underwent surgery with bilateral nerve-sparing technique and
      had sufficient follow-up. Trifecta rates applying subjective continence and
      potency definitions were 34%, 52%, 71%, and 76% at 3, 6, 12, and 24 months,
      respectively. The corresponding trifecta rates using objective continence and
      potency definitions stood at 16%, 31%, 44%, and 44%. The difference was
      statistically significant at each time point (P < .0001). CONCLUSIONS: RALP
      provides trifecta outcome rates comparable to open surgery. The outcome rates
      vary significantly depending on the tools used for continence and potency
      evaluation.

PMID- 19592076
TI  - Congenital small kidney can be an indicator of surgical treatment in children
      with primary vesicoureteral reflux.
AB  - OBJECTIVES: To evaluate the usefulness of congenital small kidney as a treatment
      indicator in children with primary vesicoureteral reflux (VUR). METHODS: Eighty
      five children aged from 1 day to 108 months with primary VUR were analyzed
      retrospectively. The children were divided into 2 groups: a normal kidney group
      (n = 45) and a small kidney group (n = 44). VUR grade, age, sex, and bilaterality
      were compared between the 2 groups. As well, the incidence of spontaneous
      resolution/improvement in VUR and antireflux surgery were compared between the 2
      groups. RESULTS: No differences were observed in either presenting age
      bilaterality or follow-up period between the 2 groups. The most common grades
      were III in the normal kidney group (20/45) and IV in the small kidney group
      (22/44). Spontaneous resolution/improvement in VUR in the normal and small kidney
      groups occurred in 11 of 20 vs 0 of 6, 6 of 15 vs 1 of 22, and 2 of 10 vs 0 of 16
      children with grades III, IV, and V, respectively. Antireflux surgery was
      performed in the normal and small kidney groups in 9 of 20 vs 6 of 6, 9 of 15 vs
      21 of 22, and 8 of 10 vs 16 of 16 children with grades III, IV, and V,
      respectively. On multivariate analysis, renal size was a statistically
      significant indicator of an antireflux surgery after adjusting for age,
      bilaterality, and VUR grade. CONCLUSIONS: Children with primary VUR accompanying
      small kidney show a lower opportunity of spontaneous resolution or improvement in
      VUR. Congenital small kidney could be an additional indicator for early surgical
      correction along with grade, age, sex, and laterality in children with primary
      VUR.

PMID- 19592077
TI  - Contemporary length of stay and resource utilization when using a fast-track
      regimen for mid-urethral sling surgery.
AB  - OBJECTIVES: To evaluate the length of stay and need for postoperative laboratory
      monitoring in a fast-track regimen, as despite the excellent safety profile of
      the tensionless synthetic midurethral sling, many advocate routine in-house
      postoperative monitoring of both vital signs and laboratory values. METHODS: A
      retrospective chart review was performed of all patients presenting for isolated,
      midurethral sling surgery by a single surgeon from February 2005 to July 2007.
      Patients followed a perioperative care pathway. Hospital charts were reviewed for
      the following data: date and time of admission to recovery, date and time of
      discharge, age, anesthetic, whether postoperative laboratory work was ordered,
      transfusion of blood, emergency room visits within 30 days, readmissions within 7
      and 30 days, and whether the patient was discharged with a catheter. RESULTS: A
      total of 112 procedures were performed. Twenty-six cases were excluded because of
      either concomitant surgical procedures (22) or incomplete data (4), resulting in
      86 patients. The median age was 52 years (range 34-89). The mean length of stay
      was 2.42 hours and the median was 2.15 hours. No postoperative laboratory tests
      were ordered and no transfusions were required. One patient presented to the
      emergency room within 30 days and was admitted for chest pain. Of 86 patients, 79
      (92%) were discharged home without a catheter. CONCLUSIONS: When following the
      fast-track regimen, the tensionless midurethral sling can be performed safely in
      the outpatient setting without postoperative laboratory work and with a median
      recovery to discharge time of < 3 hours.

PMID- 19592078
TI  - Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review
      and meta-analysis of harms.
AB  - OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo
      treated men with erectile dysfunction (ED) in a systematic review and meta
      analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified
      using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane
      CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs,
      withdrawals because of adverse events, and serious adverse events were
      ascertained and compared between sildenafil and placebo groups. The results of
      men with ED were stratified by clinical condition(s). Statistical heterogeneity
      was explored. Meta-analyses based on random-effects model were also performed.
      RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher
      risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing,
      dyspepsia, and visual disturbances compared with placebo-treated men. The
      magnitude of excess risk was greater in fixed- than in flexible-dose trials. The
      rates of serious adverse events and withdrawals because of adverse events did not
      differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded
      to a greater risk of AEs. The increased risk of harms was observed within and
      across clinically defined specific groups of patients. CONCLUSIONS: There was a
      lack of RCTs reporting long-term (>6 months) harms data. In short-term trials,
      men with ED randomized to sildenafil had an increased risk of all-cause any AEs,
      headache, flushing, dyspepsia, and visual disturbances. The exploration of
      different modes of dose optimization of sildenafil may be warranted.

PMID- 19592079
TI  - Management of women with uterine papillary serous cancer: a Society of
      Gynecologic Oncology (SGO) review.
AB  - OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a clinically and
      pathologically distinct subtype of endometrial cancer. Although less common than
      its endometrioid carcinoma (EEC) counterpart, UPSC accounts for a
      disproportionate number of endometrial cancer related deaths. To date, limited
      prospective trials exist from which evidence-based management can be developed.
      This review summarizes the available literature concerning UPSC in an effort to
      provide the clinician with information pertinent to its management. METHODS:
      MEDLINE was searched for all research articles published in English between
      January 1, 1966 and May 1, 2009 in which the studied population included women
      diagnosed with UPSC. Although preference was given to prospective studies,
      studies were not limited by design or by numbers of subjects given the paucity of
      available reports. RESULTS: UPSC is morphologically and genetically different
      from EEC. Women often present with postmenopausal vaginal bleeding, but may also
      present with abnormal cervical cytology, ascites, or a pelvic mass. In some
      cases, the diagnosis may be made with endometrial biopsy, while in other cases it
      is not made until the time of definitive surgery. Metastatic disease is common
      and best identified via comprehensive surgical staging. Local and distant
      recurrences occur frequently, with extra-pelvic relapses reported most commonly.
      Optimal cytoreduction and adjuvant platinum/taxane-based chemotherapy appear to
      improve survival, while adjuvant radiotherapy may contribute to loco-regional
      disease control. CONCLUSIONS: Women diagnosed with UPSC should undergo
      comprehensive surgical staging and an attempt at optimal cytoreduction.
      Platinum/taxane-based adjuvant chemotherapy should be considered in the treatment
      of both early- and advanced-stage patients. Careful long-term surveillance is
      indicated as many of these women will recur. Prospective clinical trials of women
      with UPSC are necessary in order to delineate the optimal therapy for women with
      newly diagnosed and recurrent disease.

PMID- 19592081
TI  - Burden of allergic rhinitis: results from the Pediatric Allergies in America
      survey.
AB  - Allergic rhinitis (AR), a chronic inflammatory disease of the upper airway, is
      one of the most common chronic diseases in the United States and is estimated to
      affect up to 60 million people. Pediatric Allergies in America is the largest and
      most comprehensive survey to date of pediatric patients and parents of patients
      with allergy, as well as health care providers (HCPs), regarding AR in children
      and its treatment. The goals of the survey were to determine the prevalence of AR
      in the US pediatric population and to collect information on what effect the
      condition has on patients in terms of symptom burden, quality of life,
      productivity, disease management, and pharmacologic treatment. This national
      survey screened 35,757 households to identify 500 children with HCP-diagnosed
      nasal allergies and 504 children without nasal allergies who were between the
      ages of 4 and 17 years. Parents of young children, as well as children 10 to 17
      years of age, were questioned about the condition and its treatment. In parallel,
      501 HCPs were interviewed. This survey has captured previously unavailable data
      on the prevalence of nasal allergies and their most common and most bothersome
      symptoms, on the effect of nasal allergies on the quality of life of children,
      and on medication use, including both over-the-counter and prescription
      medications, and has identified factors affecting satisfaction with treatment.
      The Pediatric Allergies in America survey also identifies distinct areas for
      improvement in the management of AR in children. In fact, based on the results of
      this survey, it appears that HCPs overestimate patients' and parents'
      satisfaction with disease management and the benefit of medications used for the
      treatment of nasal allergies in children. Findings from this national survey have
      identified important challenges to the management of AR, suggesting that its
      burden on children in the United States has been significantly underestimated.

PMID- 19592080
TI  - Toll-like receptor 7 and 9 defects in common variable immunodeficiency.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is characterized by
      hypogammaglobulinemia, reduced numbers of peripheral blood isotype-switched
      memory B cells, and loss of plasma cells. OBJECTIVE: Because Toll-like receptor
      (TLR) activation of B cells can initiate and potentially sustain normal B cell
      functions, we examined functional outcomes of TLR7 and TLR9 signaling in CVID B
      cells. METHODS: TLR7-mediated, TLR7/8-mediated, and TLR9-mediated cell
      proliferation, isotype switch, and immunoglobulin production by control and CVID
      B cells or isolated naive and memory B cell subsets were examined. We quantitated
      TNF-alpha, IL-6, and IL-12 production in response to TLR1-9 ligands and measured
      IFN-alpha production by TLR7-stimulated PBMCs and isolated plasmacytoid dendritic
      cells (pDCs). IFN-beta mRNA expression by TLR3-stimulated fibroblasts was
      assessed. RESULTS: Unlike CD27(+) B cells of controls, TLR7-activated, TLR7/8
      activated, or TLR9-activated CVID B cells or isolated CD27(+) B cells did not
      proliferate, upregulate CD27, or shed surface IgD. TLR-stimulated CVID B cells
      failed to upregulate activation-induced cytosine deaminase mRNA or produce IgG
      and IgA. TLR7-stimulated PBMCs and pDCs produced little or no IFN-alpha.
      Reconstituting IFN-alpha in TLR7-stimulated CVID B-cell cultures facilitated
      proliferation, CD27 upregulation, and isotype switch. These TLR defects are
      restricted because CVID PBMCs stimulated with TLR ligands produced normal amounts
      of TNF-alpha, IL-6, and IL-12; TLR3-mediated expression of IFN-beta by CVID
      fibroblasts was normal. CONCLUSION: Defective TLR7 and TLR9 signaling in CVID B
      cells and pDCs, coupled with deficient IFN-alpha, impairs CVID B cell functions
      and prevents TLR-mediated augmentation of humoral immunity in vivo.

PMID- 19592083
TI  - Effects of ethanol addition on the water sorption/solubility and percent
      conversion of comonomers in model dental adhesives.
AB  - OBJECTIVES: This study evaluated the kinetics of water uptake and percent
      conversion in neat versus ethanol-solvated resins that were formulated to be used
      as dental bonding agents. METHODS: Five methacrylate-based resins of known and
      increasing hydrophilicities (R1, R2, R3, R4 and R5) were used as reference
      materials. Resins were evaluated as neat bonding agents (100% resin) or they were
      solvated with absolute ethanol (95% resin/5% ethanol or 85% resin/15% ethanol).
      Specimens were prepared by dispensing the uncured resin into a circular mold (5.8
      mm x 0.8 mm). Photo-activation was performed for 80s. The water
      sorption/diffusion/solubility was gravimetrically evaluated, while the degree of
      conversion (DC) was calculated by Fourier-transform infrared spectroscopy.
      RESULTS: Water sorption increased with the hydrophilicity of the resin blends. In
      general, the solvated resins exhibited significantly higher water sorption,
      solubility and water diffusion coefficients when compared to their corresponding
      neat versions (p<0.05). The only exception was resin R1, the least hydrophilic
      resin, in which neat and solvated versions exhibited similar water sorption
      (p>0.05). Addition of ethanol increased the DC of all resins tested, especially
      of the least hydrophilic, R1 and R2 (p<0.05). Despite the increased DC of ethanol
      solvated methacrylate-based resins, it occurs at the expense of an increase in
      their water sorption/diffusion and solubility values. SIGNIFICANCE: Negative
      effects of residual ethanol on water sorption/solubility appeared to be greater
      as the hydrophilicity of the resin blends increased. That is, the use of less
      hydrophilic resins in dental adhesives may create more reliable and durable bonds
      to dentin.

PMID- 19592082
TI  - Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic
      stem cells.
AB  - Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first
      cyclin ever cloned, is thought to be an essential component of the cell-cycle
      engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and
      ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A
      function using conditional knockout mice lacking both A-type cyclins. We found
      that acute ablation of cyclin A in fibroblasts did not affect cell proliferation,
      but led to prolonged expression of another cyclin, cyclin E, across the cell
      cycle. However, combined ablation of all A- and E-type cyclins extinguished cell
      division. In contrast, cyclin A function was essential for cell-cycle progression
      of hematopoietic and embryonic stem cells. Expression of cyclin A is particularly
      high in these compartments, which might render stem cells dependent on cyclin A,
      whereas in fibroblasts cyclins A and E play redundant roles in cell
      proliferation.

PMID- 19592084
TI  - Response of the Arabian Sea to global warming and associated regional climate
      shift.
AB  - The response of the Arabian Sea to global warming is the disruption in the
      natural decadal cycle in the sea surface temperature (SST) after 1995, followed
      by a secular warming. The Arabian Sea is experiencing a regional climate-shift
      after 1995, which is accompanied by a five fold increase in the occurrence of
      "most intense cyclones". Signatures of this climate-shift are also perceptible
      over the adjacent landmass of India as: (1) progressively warmer winters, and (2)
      decreased decadal monsoon rainfall. The warmer winters are associated with a 16
      fold decrease in the decadal wheat production after 1995, while the decreased
      decadal rainfall was accompanied by a decline of vegetation cover and increased
      occurrence of heat spells. We propose that in addition to the oceanic thermal
      inertia, the upwelling-driven cooling provided a mechanism that offset the CO(2)
      driven SST increase in the Arabian Sea until 1995.

PMID- 19592085
TI  - Radiopaque iodinated copolymeric nanoparticles for X-ray imaging applications.
AB  - Recently we described iodinated homopolymeric radiopaque nanoparticles of 28.9+/
      6.3 nm dry diameter synthesized by emulsion polymerization of 2
      methacryloyloxyethyl(2,3,5-triiodobenzoate) (MAOETIB). The nanoparticle aqueous
      dispersion, however, was not stable and tended to agglomerate, particularly at
      weight concentration of dispersed nanoparticles above approximately 0.3%. The
      agglomeration rate increases as the concentration of nanoparticles in aqueous
      phase rises and prevents the potential in vivo use as contrast agent for medical
      X-ray imaging. Here we describe efforts to overcome this limitation by synthesis
      of iodinated copolymeric nanoparticles of 25.5+/-4.2 nm dry diameter, by emulsion
      copolymerization of the monomer, MAOETIB, with a low concentration of glycidyl
      methacrylate (GMA). The surface of resulting copolymeric nanoparticles is far
      more hydrophilic than that of polyMAOETIB (PMAOETIB) nanoparticles. Therefore,
      P(MAOETIB-GMA) nanoparticles are significantly more stable against agglomeration
      in aqueous continuous phase. After intravenous injection of P(MAOETIB-GMA)
      nanoparticles in rats and mice (including those with a liver cancer model) CT
      imaging revealed a significant enhanced visibility of the blood pool for 30 min
      after injection. Later, lymph nodes, liver and spleen strongly enhanced due to
      nanoparticle uptake by the reticuloendothelial system. This favorably enabled the
      differentiation of cancerous from healthy liver tissue and suggests our particles
      for tumor imaging in liver and lymph nodes.

PMID- 19592086
TI  - Physical approaches for fabrication of organized nanostructure of resilin-mimetic
      elastic protein rec1-resilin.
AB  - Protein adsorption on surfaces is a fundamental step in many applications. While
      various methods such as lithography, self assembly using nanoparticles, layer-by
      layer attachment, etc. have been employed, here we report fabrication of
      controlled nanostructure of a new resilin-mimetic elastic protein rec1-resilin
      using physical approaches. We investigate the assembly, morphology and tunability
      of the nanostructure of adsorbed rec1-resilin architectures by atomic force
      microscopy (AFM) and scanning thermal microscopy (SThm) demonstrating that the
      protein conformation and structure during assembly can be controlled by tuning
      the physical conditions at the surface. Our findings show distinct morphology and
      height of monomolecular rec1-resilin film, dependent on substrate surface energy.
      We also show that these heights, a function of molecular orientation, can be
      maintained on swelling and drying.

PMID- 19592088
TI  - Tissue assembly and organization: developmental mechanisms in microfabricated
      tissues.
AB  - In vitro-generated tissues hold significant promise in modern biology since they
      can potentially mimic physiological and pathological tissues. However, these are
      currently structurally and functionally of limited complexity and necessitate
      self-organization and recapitulation of tissue development mechanisms in vitro.
      Tools derived from nano- and microfabrications along with bottom-up strategies
      are emerging to allow the fabrication of primitive tissues structures that can
      remodel overtime. Subsequently, clues are accumulating to show that, beyond
      genetic material, both intrinsic tissue architectures and microenvironmental cues
      can lead to morphogenesis related mechanisms in vitro. The question arises,
      however, as how we may design and assemble structures prone to adequate tissue
      remodeling, predict and manipulate those developmental mechanisms in vitro?
      Systems integrating architectural, physical and molecular cues will allow more
      systematic investigation of basic principles of tissue morphogenesis,
      differentiation or maintenance and will feedback to reproduce the dynamic of
      tissue development in vitro and form more complex tissues.

PMID- 19592087
TI  - Nanostructured hybrid hydrogels prepared by a combination of atom transfer
      radical polymerization and free radical polymerization.
AB  - A new method to prepare nanostructured hybrid hydrogels by incorporating well
      defined poly(oligo (ethylene oxide) monomethyl ether methacrylate) (POEO(300)MA)
      nanogels of sizes 110-120 nm into a larger three-dimensional (3D) matrix was
      developed for drug delivery scaffolds for tissue engineering applications.
      Rhodamine B isothiocyanate-labeled dextran (RITC-Dx) or fluorescein
      isothiocyanate-labeled dextran (FITC-Dx)-loaded POEO(300)MA nanogels with pendant
      hydroxyl groups were prepared by activators generated electron transfer atom
      transfer radical polymerization (AGET ATRP) in cyclohexane inverse miniemulsion.
      Hydroxyl-containing nanogels were functionalized with methacrylated groups to
      generate photoreactive nanospheres. (1)H NMR spectroscopy confirmed that
      polymerizable nanogels were successfully incorporated covalently into 3D
      hyaluronic acid-glycidyl methacrylate (HAGM) hydrogels after free radical
      photopolymerization (FRP). The introduction of disulfide moieties into the
      polymerizable groups resulted in a controlled release of nanogels from cross
      linked HAGM hydrogels under a reducing environment. The effect of gel
      hybridization on the macroscopic properties (swelling and mechanics) was studied.
      It is shown that swelling and nanogel content are independent of scaffold
      mechanics. In-vitro assays showed the nanostructured hybrid hydrogels were
      cytocompatible and the GRGDS (Gly-Arg-Gly-Asp-Ser) contained in the nanogel
      structure promoted cell-substrate interactions within 4 days of incubation. These
      nanostructured hydrogels have potential as an artificial extracellular matrix
      (ECM) impermeable to low molecular weight biomolecules and with controlled
      pharmaceutical release capability. Moreover, the nanogels can control drug or
      biomolecule delivery, while hyaluronic acid based-hydrogels can act as a
      macroscopic scaffold for tissue regeneration and regulator for nanogel release.

PMID- 19592089
TI  - Simultaneous release of multiple molecules from poly(lactide-co-glycolide)
      nanoparticles assembled onto medical devices.
AB  - Cell and tissue responses to implanted biomaterials often limit their
      effectiveness and lifetime. This is particularly true for materials implanted
      into the brain. We present here a new approach for the modification of materials
      to enable release of multiple agents, which might be useful in modulating tissue
      responses, without changing the properties of the underlying material, in this
      case, a silicon probe. Poly(lactide-co-glycolide) nanoparticles (NPs) were
      assembled onto silicon probe surfaces by electrostatic interactions. Charged NPs
      were fabricated by altering the properties of the surfactant. NPs formed with
      poly(ethylene-alt-maleic anhydride) (PEMA) were strongly negatively charged;
      these NPs assembled onto probes best when suspended at nearly physiological
      conditions (surface density approximately 83,600+/-3000 particles/mm(2)). The
      percentage of surface area coverage by the NPs was estimated to be approximately
      13% and was maintained over two weeks during constant exposure to PBS. Multiple
      fluorescent NP populations were attached to the same probe to allow visualization
      of simultaneous delivery of multiple agents by fluorescence microscopy. Release
      from NP coatings was reproducible and controllable. The distinct release profiles
      of each agent from the coatings were preserved upon attachment to the surfaces.
      The unique feature of this new system is that NPs encapsulating various molecules
      (i.e. drugs, proteins, or DNA) can be fabricated separately, in advance, and
      simply mixed prior to attachment. The versatility of this delivery system,
      therefore, makes it suitable for many applications.

PMID- 19592090
TI  - Cell adhesion on phase-separated surface of block copolymer composed of poly(2
      methacryloyloxyethyl phosphorylcholine) and poly(dimethylsiloxane).
AB  - We investigated the morphological effect of phase-separated block copolymer
      surfaces composed of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) (PMPC)
      and poly(dimethylsiloxane) (PDMS) on protein adsorption and cell adhesion
      behavior. We observed three different types of phase-separated surface
      morphologies by TEM and AFM. The elemental composition of phosphorus on the
      surface increases with the PMPC composition. Furthermore, the polymer surface
      formed by a block copolymer-containing a higher MPC unit composition shows a
      slightly lower static water contact angle. This result indicates that the
      elemental surface ratio of the surface depends on the MPC composition in the
      block copolymer. Protein adsorption tests revealed that only hydrophobic PDMS
      domains showed selective protein adsorption. Cell adhesion tests revealed that
      the number of adhered cells increased with increasing hydrophobic PDMS domain
      size of block copolymers in serum-containing media. In contrast, no cells adhered
      onto block copolymer surfaces in serum-free media, whereas a large amount of
      adhered cells were observed on the hydrophobic PDMS surface. This result
      indicates that segregated hydrophobic domains on a biocompatible PMPC surface
      strongly affect serum protein adsorption, thereby promoting considerable cell
      adhesion, although the surface is hydrophilic. Thus, both the composition of MPC
      units and the segregated hydrophobic surface morphology are important
      considerations in biomaterial surface design.

PMID- 19592091
TI  - A delayed yet durable response to very short lenalidomide therapy and unexpected
      clone redistribution in a case of myelodysplastic syndrome with del(5q) and
      del(20q).

PMID- 19592092
TI  - Evolving systems of care with total clinical outcomes management.
AB  - The current article proposes that further specification of the system of care
      concept is required. Based on the assertions that the system of care concept (a)
      refers to an ideal as opposed to an observable phenomenon, and (b) is engaged in
      offering transformational experiences, the authors propose that the system of
      care definition must be expanded to include measurement and outcomes monitoring
      strategies that extend beyond current quality improvement initiatives. The
      authors propose that communication across multiple levels is essential if the
      goal of offering transformational experiences to children and families is to be
      realized.

PMID- 19592093
TI  - How states, tribes and localities are re-defining systems of care.
AB  - The original definition of system of care was developed 20 years ago largely in
      response to the fragmented services experienced by children with serious
      emotional disorders and their families, who, typically, were involved in multiple
      systems and/or receiving services from different providers. Over time, in
      response to national funders' pursuing system of care for different populations
      and their own experience, states, tribes and localities have applied system of
      care principles, values and operational characteristics to other populations
      (children and adults). The definition offered by Hodges et al., has an unintended
      effect of constraining the properties (and potential) of system of care in its
      limitation to a single population. This paper argues that the adaptations made to
      the original Stroul and Friedman definition in the training curriculum Building
      Systems of Care: A Primer adequately encompass properties that reflect state,
      tribal and local implementation experience and are specific to planning,
      implementing and evaluating a system of care, without limiting system of care to
      any one population.

PMID- 19592094
TI  - Which compounds contribute most to elevated airborne exposure and corresponding
      health risks in the Western Balkans?
AB  - A majority of ongoing monitoring of persistent organic pollutants (POPs) is
      currently focused on chemicals emphasized in the Stockholm Convention.
      Quantitative detection of other substances (especially those with numerous
      anthropogenic sources such as polyaromatic hydrocarbons (PAHs)) is, however, also
      needed since their concentrations are usually several orders of magnitude higher.
      A goal of this study was to determine how various groups of compounds contribute
      to total human health risks at the variety of sampling sites in the region of
      Western Balkan. Distribution of the risks between the gas and particulate phases
      was also addressed. Results showed that inhalation exposure to organochlorine
      pesticides (OCPs) does not represent a significant risk to humans, while
      polychlorinated biphenyls (PCBs) re-volatilized to the atmosphere from
      contaminated soils and buildings can pose a problem. PCB evaporation from primary
      sources (currently used PCB-filled transformers or non-adequate storage
      facilities) generally resulted in much higher atmospheric concentrations than
      evaporation from the secondary sources (soils at the sites of war destructions).
      A majority of the human health risks at the urban sites were associated with
      PAHs. Between 83 and 94% of the cumulative risk at such sites was assigned to
      chemicals sorbed to particles, and out of it, PAHs were responsible for 99%.

PMID- 19592095
TI  - Exposure to cigarette smoke suppresses IL-15 generation and its regulatory NK
      cell functions in poly I:C-augmented human PBMCs.
AB  - Both NK cells and IL-15 play crucial roles in innate immunity against viral
      infections and cancer. Cigarette smoke is known to increase susceptibility to
      infections and certain cancers. Interleukin (IL)-15 plays an important role in
      immune responses by regulating proliferation, survival and functions of NK cells.
      Here, we examined the impact of cigarette smoke on IL-15 production and IL-15
      mediated NK cell functions in human PBMCs. We report that cigarette smoke
      significantly suppresses the induction of IL-15 by poly I:C in human PBMCs. Serum
      IL-15 levels among smokers was significantly lower than non-smokers. In contrast
      to a profound increases in intracellular IL-15/IL-15Ralpha in poly I:C-treated
      PBMCs, exposure of PBMCs to smoke-conditioned media (SCM) diminished the IL-15/IL
      15Ralpha production. We examined if inhibition of IL-15 production could lead to
      less NK cell activation. Interestingly, SCM-treated PBMCs had diminished up
      regulation of NK cell activation marker, CD69, but not NKG2D compared with
      controls after poly I:C stimulation. We then confirmed by using IL-15
      neutralizing antibody as well as exogenous IL-15 that the ploy I:C-induced NK
      cells activation was IL-15 mediated. More importantly, cigarette smoke
      significantly impaired NK cell cytolytic potential to kill K562 cancer cells
      which was found to be IL-15 mediated. The inhibition of IL-15 and its regulatory
      NK cell activities were linked to attenuated STAT3 and STAT5, but not ERK1/2
      phosphorylations. We demonstrate, for the first time, that cigarette smoke
      compromises IL-15 production and as a result NK cell function which could link to
      the higher incidence of cancers or viral infections observed among smokers.

PMID- 19592098
TI  - Altered hepatic mRNA expression of immune response and apoptosis-associated genes
      after acute and chronic psychological stress in mice.
AB  - Using a combination of transcriptional profiling and Ingenuity Pathway Analysis
      (IPA, www.ingenuity.com) we investigated acute and chronic psychological stress
      induced alterations of hepatic gene expression of BALB/c mice. Already after a 2
      h single stress session, up-regulation of several LPS and glucocorticoid
      sensitive immune response genes and markers related to oxidative stress and
      apoptotic processes were observed. Support for the existence of oxidative stress
      was gained by measuring increased protein carbonylation, but no alterations of
      immune responsiveness or cell death were measured in mice after acute stress
      compared to the control group. When animals were repeatedly stressed during 4.5
      days, we found reduced transcription of antigen presentation molecules, altered
      mRNA levels of immune cell signaling mediators and persisting high expression of
      apoptosis-related genes. These alterations were associated with a measurable
      immune suppression characterized by a reduced ability to clear experimental
      Salmonella typhimurium infection from the liver and a heightened hepatocyte
      apoptosis. Moreover, genes associated with anti-oxidative functions and
      regenerative processes were induced in the hepatic tissue of chronically stressed
      mice. These findings indicate that modulation of the immune response and of
      apoptosis-related genes is initiated already during a single acute stress
      exposure. However, immune suppression will only manifest in repeatedly stressed
      mice which additionally show induction of protective and liver regenerative genes
      to prevent further hepatocyte damage.

PMID- 19592096
TI  - Promoter activity 5' of Dbeta2 is coordinated by E47, Runx1, and GATA-3.
AB  - V(D)J recombination involves the stepwise assembly of B and T cell receptor genes
      as lymphocytes progress through the early stages of development. While the
      mechanisms that restrict each step in recombination to its appropriate
      developmental stage are largely unknown, they share many of the components that
      regulate transcription. For example, enhancer-dependent modifications in histone
      acetylation and methylation are essential for both germline transcription and
      rearrangement of antigen receptor genes. Promoters positioned proximal to
      individual D and J gene segments in Tcra, Tcrb, Tcrd, IgH, and Igk also
      contribute to antigen receptor gene assembly, though their effects appear more
      localized than those of enhancers. Tcrb assembly initiates with D-to-J joining at
      each of the two D-J-C gene segment clusters in DN1/2 thymocytes. DJ joints are
      fused with Vbeta elements to complete Tcrb recombination in DN3 cells. We have
      previously shown that Dbeta2 is flanked by upstream and downstream promoters,
      with the 5' promoter being held inactive until D-to-J recombination deletes the
      NFkappaB-dependent 3' promoter. We now report that activity of the 5' promoter
      reflects a complex interplay among Runx1, GATA-3, and E47 transcription factors.
      In particular, while multiple E47 and Runx1 binding sites clustered near the
      Dbeta2 5'RS and overlapping inr elements define the core 5'PDbeta2, they act in
      concert with an array of upstream GATA-3 sites to overcome the inhibitory effects
      of a 110bp distal polypurine.polypyrimidine (R.Y) tract. The dependence of
      5'PDbeta2 on E47 is consistent with the reported role of E proteins in post-DN1
      thymocyte development and V-to-DJbeta recombination.

PMID- 19592099
TI  - Observations about objective and subjective ocular torsion.
AB  - OBJECTIVE: To investigate the relationship between objective and subjective
      torsion in patients with cyclovertical strabismus and determine whether objective
      torsion differs according to which eye is fixing. DESIGN: A prospective
      evaluation of tests of objective and subjective torsion. PARTICIPANTS: Thirty-six
      patients with various types of cyclovertical strabismus. METHODS: Subjective
      torsion was assessed with the double Maddox rod, and objective torsion was graded
      in a masked manner from fundus photographs. MAIN OUTCOME MEASURES: Quantification
      of objective or subjective torsion. RESULTS: Objective torsion was the same
      regardless of which eye was used for fixation. However, after prolonged occlusion
      of the nonaffected eye, there was often an increase in objective torsion in the
      nonaffected eye. Subjective torsion typically was absent in patients with
      objective torsion if they did not have bifoveal fusion but was similar to
      objective torsion in patients with bifoveal fusional potential. CONCLUSIONS:
      Assessment of objective and subjective torsion are each important but play
      separate roles in the evaluation of cyclovertical strabismus. There is no
      immediate torsional motor shift when fixation switches from the nonaffected to
      the affected eye. However, prolonged fixation of the affected eye may possibly
      result in a motor torsional change in the nonaffected eye in some patients.

PMID- 19592097
TI  - Continual signaling is responsible for constitutive ERK phosphorylation in B-1a
      cells.
AB  - B-1a cells constitutively express phosphorylated, activated ERK, but the origin
      of pERK in B-1 cells has not been determined. To address this issue, we examined
      specific mediators of intracellular signaling in unmanipulated B-1a cells. We
      found that constitutive pERK was rapidly lost from B-1a cells following addition
      of metabolic inhibitors that block src kinase, Syk, PI-3K, and PLC function. We
      examined Syk and PLC in more detail and found rapid accumulation of
      phosphorylated forms of these molecules in B-1a cells, but not B-2 cells, when
      phosphatase activity was inhibited, and this change occurred in the majority of B
      1a cells. Further, we showed that inhibition of src kinase activity eliminated
      "downstream" pSyk and pPLC accumulation in phosphatase-inhibited B-1a cells,
      indicating a pathway connection. CD86 expression is greater on B-1 than B-2 cells
      and plays a role in antigen presentation by B-1 cells to T cells. We found that
      when Syk or PI-3K was inhibited, CD86 expression was diminished in a reversible
      fashion. All together, these results indicate that continual activation of
      intracellular signaling leads to constitutive activation of ERK in B-1 cells,
      with attendant consequences for co-stimulatory molecule expression.

PMID- 19592100
TI  - Genetic etiology and clinical consequences of complete and incomplete
      achromatopsia.
AB  - OBJECTIVE: To investigate the genetic causes of complete and incomplete
      achromatopsia (ACHM) and assess the association between disease-causing
      mutations, phenotype at diagnosis, and visual prognosis. DESIGN: Clinic-based,
      longitudinal, multicenter study. PARTICIPANTS: Probands with complete ACHM (n =
      35), incomplete ACHM (n = 26), or nonspecific ACHM (n = 2) and their affected
      relatives (n = 18) from various ophthalmogenetic clinics in The Netherlands.
      METHODS: Ophthalmologic clinical data were assessed over a life time and were
      registered from medical charts and updated by ophthalmologic examination.
      Mutations in the CNGB3, CNGA3, and GNAT2 genes were analyzed by direct
      sequencing. MAIN OUTCOME MEASURES: Genetic mutations and clinical course of ACHM.
      RESULTS: CNGB3 mutations were identified in 55 of 63 (87%) of probands and all
      caused premature truncation of the protein. The most common mutation was
      p.T383IfsX13 (80%); among the 4 other mutations was the novel frameshift mutation
      p.G548VfsX35. CNGA3 mutations were detected in 3 of 63 (5%) probands; all caused
      an amino acid change of the protein. No mutations were found in the GNAT2 gene.
      The ACHM subtype, visual acuity, color vision, and macular appearance were
      equally distributed among the CNGB3 genotypes, but were more severely affected
      among CNGA3 genotypes. Visual acuity deteriorated from infancy to adulthood in
      12% of patients, leading to 0.10 in 61%, and even lower than 0.10 in 20% of
      patients. CONCLUSIONS: In this well-defined cohort of ACHM patients, the disease
      seemed much more genetically homogeneous than previously described. The CNGB3
      gene was by far the most important causal gene, and T383IfsX13 the most frequent
      mutation. The ACHM subtype did not associate with a distinct genetic etiology,
      nor were any other genotype-phenotype correlations apparent. The distinction
      between complete and incomplete subtypes of ACHM has no clinical value, and the
      assumption of a stationary nature is misleading.

PMID- 19592101
TI  - Natural history of predominantly classic, minimally classic, and occult subgroups
      in exudative age-related macular degeneration.
AB  - OBJECTIVES: We previously showed that the pattern of vision loss in eyes with
      subfoveal neovascularization in age-related macular degeneration (AMD) is uniform
      across a wide range of clinical trials, with apparent differences arising from
      differences in the time of entry of patients into clinical trials. In the current
      study, we used a similar analysis to compare the visual loss of untreated control
      eyes classified as predominantly classic (PC), minimally classic (MC), and occult
      with no classic (occult) based on fluorescein angiography. DESIGN: Meta-analysis
      of prior clinical trials. PARTICIPANTS: Data from patients enrolled in the
      Macular Photocoagulation Study (MPS), Treatment of Age-related Macular
      Degeneration with Photodynamic Therapy (TAP) Study, Verteporfin in Photodynamic
      Therapy (VIP) Study, Anecortave Acetate (AA) Trial, VEGF Inhibition Study in
      Ocular Neovascularization (VISION), and Minimally Classic/Occult Trial of the
      Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related
      Macular Degeneration (MARINA) Trials. METHODS: Visual acuity (VA) data of
      untreated control eyes for each study from appropriate subgroups were plotted on
      a double reciprocal (Lineweaver-Burke) plot of 1/[letters lost] versus
      1/[months]. To correct for differences in time of entry into clinical trials, we
      introduced a horizontal translation factor to shift each data subset. MAIN
      OUTCOME MEASURES: We determined the coefficient of determination before and after
      adjustments for visual acuity at the time of enrollment. RESULTS: On a Lineweaver
      Burke plot, the cumulative subgroups had an overall coefficient of determination
      of only r(2)<0.01 for the raw data but improved to a remarkably high r(2) = 0.90
      when data were corrected for time of entry into clinical trials. For each
      subgroup there was excellent correlation between 1/[letters lost] versus
      1/[months of exudative disease] for PC (r(2) = 0.91), MC (r(2) = 0.95), and
      occult (r(2) = 0.98) choroidal neovascularization. CONCLUSIONS: We were able to
      demonstrate a strong correlation for visual acuity as a function of time that is
      independent of the fluorescein angiography classification of a lesion, suggesting
      that initial protocol visual acuity, rather than angiographic classification, is
      the major determinant of the behavior of visual acuity as a function of time in
      exudative AMD.

PMID- 19592102
TI  - Age-related macular degeneration and risk of coronary heart disease and stroke:
      the Cardiovascular Health Study.
AB  - PURPOSE: To examine the associations of age-related macular degeneration (AMD)
      with incident coronary heart disease (CHD) and stroke in the Cardiovascular
      Health Study. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A
      total of 1786 white and African-American participants free of CHD or 2228
      participants free of stroke, aged 69 to 97 years. METHODS: AMD was evaluated from
      photographs taken in 1997 and 1998. MAIN OUTCOME MEASURES: Incident CHD and
      stroke ascertained using standardized methods. RESULTS: Of the 1786 persons free
      of CHD, 303 developed incident CHD over 7 years. Participants with early AMD (n =
      277) had a higher cumulative incidence of CHD than participants without early AMD
      (25.8% vs. 18.9%, P = 0.001). By adjusting for age, gender, race, systolic and
      diastolic blood pressure, hypertension status, fasting glucose, triglyceride, low
      density lipoprotein cholesterol, cigarette smoking, pack years of smoking, and C
      reactive protein, the presence of early AMD was associated with an increased risk
      of incident CHD (hazard ratio 1.57; 95% confidence interval, 1.17-2.22). Late AMD
      (n = 25) was not associated with incident CHD (hazard ratio 0.78; 95% confidence
      interval, 0.25-2.48). Among 2228 persons at risk, 198 developed incident stroke;
      neither early nor late AMD was associated with incident stroke. CONCLUSIONS: This
      study suggests persons with early AMD have a higher risk of CHD but not stroke in
      a population aged 69 to 97 years. This provides further support that AMD is
      associated with underlying systemic vascular disease.

PMID- 19592103
TI  - A randomized, clinical trial evaluating ready-made and custom spectacles
      delivered via a school-based screening program in China.
AB  - PURPOSE: We sought to evaluate visual performance and satisfaction with ready
      made spectacles (RMS) in Chinese school-aged children with uncorrected refractive
      error. DESIGN: Randomized, double-blind, clinical trial. PARTICIPANTS: Junior
      high school students from urban Guangzhou, China, aged approximately 12 to 15
      years with > or =1 diopter (D) of uncorrected spherical equivalent (SE)
      refractive error. Students were excluded with > or =2.00 D astigmatism, > or =2 D
      myopic anisometropia, and > or =1 D hyperopic anisometropia and ocular disease
      affecting vision. METHODS: Refractive error was determined by cycloplegic
      subjective refraction. Students were randomly assigned to receive RMS or custom
      spectacles (CS) and assessed after 1 month of use. We required 175 students to
      complete in each arm to be able to measure a 15% difference in compliance. MAIN
      OUTCOME MEASURES: Compliance with spectacles lens wear, patterns of use, vision,
      symptoms, and perceived value. RESULTS: Screening identified 965 of 4607 (20.9%)
      students with reduced distance vision; 212 of the 965 (22.0%) refused evaluation
      and 187 of the 965 (20.8%) had <1 D of SE refractive error. Sixty-one (6.3%) were
      referred for further evaluation and the remaining 495 (51.3%) participated.
      Social, demographic, and ocular parameters were similar in the 2 groups. Average
      SE refractive error was -2.57+/-1.31 (mean value +/- standard deviation [SD]).
      Spectacle vision (Snellen acuity, mean +/- SD) was worse with RMS in the eye with
      lower SE (20/25(-0.5)+/-0.9 lines vs 20/25(+1)+/-0.7 lines; P = 0.004) and higher
      SE (20/25(-2)+/-1.2 lines vs 20/25(+1)+/-0.8; P<0.001). There were no differences
      (P>0.05) in the rate of use (94.3% vs 92.2%), wearing to the 1-month visit (46.9%
      vs 51.5%), planned use (93.3% vs 93.7%), value (89.5% vs 91.7% "moderate or high
      value or most valued possession"), or symptoms (blur, 21.1% vs 19.4% [P = 0.8]
      and other symptoms [P>0.2]). CONCLUSIONS: Although visual acuity was better with
      CS, no difference was found in acceptability in this population of students with
      predominantly simple myopic refractive error. This study supports the use of RMS
      in a school-based refractive services program, saving costs and improving the
      logistics of service delivery.

PMID- 19592104
TI  - Orbital septum attachment on the levator aponeurosis in Asians: in vivo and
      cadaver study.
AB  - PURPOSE: To examine the anatomic relationships between the preaponeurotic fat
      pad, orbital septum, and the distal end of the anterior layer of the levator
      aponeurosis (DEALLA) in relation to the superior tarsal plate border. DESIGN:
      Prospective, clinical case series and experimental anatomic study. PARTICIPANTS:
      Twenty-two upper eyelids in 11 Asian patients (average age, 76.5 years) and 10
      postmortem upper eyelid specimens of 7 Asians (average age, 81 years). METHODS:
      The relationships between the orbital septum, DEALLA, preaponeurotic fat pad, and
      the superior tarsal plate border were examined in vivo, during upper
      blepharoplasty. In cadavers, the orbital septum was exposed and excised from the
      DEALLA, and the distance from the superior tarsal plate border to the DEALLA was
      measured at 3 points: the center of the palpebral width, and 2 points located 7
      mm medial and lateral to the center. MAIN OUTCOME MEASURES: The anatomic
      relationships of the orbital septum, DEALLA, and the preaponeurotic fat pad with
      the superior tarsal plate border. RESULTS: In vivo, the DEALLA was always located
      above the superior tarsal plate border, and the lower margin of the
      preaponeurotic fat was always positioned below the DEALLA and around the superior
      tarsal plate border. The lateral preaponeurotic fat in 4 eyelids showed extension
      beyond the superior tarsal border. In cadavers, the average distance from the
      superior tarsal plate border to the DEALLA was 3.7 mm centrally, 3.0 mm medially,
      and 0.9 mm laterally. In 3 specimens, the confluent part of the orbital septum
      and the levator aponeurosis reached the tarsus in the lateral area. CONCLUSIONS:
      Orbital septum attachment on the levator aponeurosis in Asians seems to be
      situated above the superior tarsal plate border in vivo, but the preaponeurotic
      fat extends beyond the DEALLA, sometimes reaching the tarsal plate. In some
      cadavers, the confluent part was found to be situated on the tarsus laterally.

PMID- 19592105
TI  - Two-year survival of Ahmed valve implantation in the first 2 years of life with
      and without intraoperative mitomycin-C.
AB  - PURPOSE: To evaluate the effect of intraoperative mitomycin-C (MMC) on
      polypropylene Ahmed glaucoma valve (AGV) survival 2 years after implantation
      during the first 2 years of life. DESIGN: Retrospective institutional comparative
      series (1995-2005). PARTICIPANTS: Thirty-one eyes of 27 patients (23 unilateral,
      4 bilateral; 16 boys, 11 girls) undergoing AGV implantation at a mean age of 11.1
      months (standard deviation [SD], 5.46), all of which had 2 years of regular
      postoperative follow-up. MMC was applied intraoperatively in those cases in the
      area of AGV implantation in 16 (52%) and was not applied in 15 (48%). In some
      eyes, MMC was applied intraoperatively in cases done by the surgeons who
      routinely used MMC for all AGV implantation in young children. METHODS: Failure
      was defined as intraocular pressure (IOP) > 22 mmHg with or without glaucoma
      medications, the need for an additional procedure for IOP control, or the
      occurrence of significant complications (e.g., endophthalmitis, retinal
      detachment, persistent hypotony [IOP < 5 mmHg]). Survival was the absence of
      failure. MAIN OUTCOME MEASURES: Failure or significant complications as defined.
      RESULTS: Mean survival for the non-MMC eyes (22.15 months; standard error [SE],
      1.93) was significantly longer than survival for the MMC eyes (16.25 months; SE,
      2.17) by the log-rank test (P = 0.025). The difference in cumulative survival at
      2 years was also significantly different by log-rank test (P = 0.001): 80.0% (SE
      10.3) and 31.3% (SE 11.6), respectively. CONCLUSIONS: Rather than improved
      survival, intraoperative use of MMC was associated with shorter survival 2 years
      after AGV implantation during the first 2 years of life. We speculate that MMC
      induced tissue death can stimulate a reactive fibrosis around the AGV in very
      young eyes.

PMID- 19592107
TI  - Endothelial keratoplasty: the use of viscoelastic as an aid in reattaching the
      dislocated graft in abnormally structured eyes.
AB  - PURPOSE: To explore the feasibility of reattaching the dislocated graft with
      viscoelastic in abnormally structured eyes after Descemet-stripping automated
      endothelial keratoplasty (DSAEK). DESIGN: Retrospective case series.
      PARTICIPANTS: Five pseudophakic bullous keratopathy cases (5 eyes) with a history
      of vitrectomy and/or iris-lens diaphragm injury. METHODS: After DSAEK, graft
      dislocation occurred in each of the 5 cases (5 eyes). We attempted to fill the
      anterior chamber (AC) with an air bubble to push up the dislocated graft, but
      this was not successful. We then injected balanced salt solution into the
      vitreous body to obtain normal intraocular pressure (IOP) and injected a small
      amount of viscoelastic (Healon GV) to support the AC. Next, we injected an air
      bubble into the AC. MAIN OUTCOME MEASURES: The position of the grafts was checked
      with a slit lamp and anterior segment optical coherence tomography (AS-OCT). The
      IOP was observed with Goldmann tonometer. The best visual acuity was checked.
      RESULTS: As observed through the slit lamp and AS-OCT, the grafts reattached well
      in all patients. The IOP was normal in all patients except one, who had high IOP
      1 month postoperatively. After receiving drug treatment, the patient's IOP
      returned to normal. The grafts had slight edema on postoperative day 1, but
      became transparent between days 5 and 8. CONCLUSIONS: Viscoelastic aided in the
      reattachment of the dislocated graft in eyes with a history of vitrectomy and/or
      iris-lens diaphragm injury. The presence of viscoelastic in the AC in the early
      period of post-DSAEK was well tolerated in this small series.

PMID- 19592106
TI  - Prevalence and causes of visual impairment in African-American and Hispanic
      preschool children: the multi-ethnic pediatric eye disease study.
AB  - PURPOSE: To determine the prevalence and causes of decreased visual acuity (VA)
      in a population-based study of minority preschool children. DESIGN: Population
      based, cross-sectional study. PARTICIPANTS: Children 30 to 72 months of age in 44
      census tracts in Los Angeles County. METHODS: A population-based sample of
      children underwent comprehensive ophthalmic evaluation including monocular VA
      testing, cover testing, cycloplegic autorefraction, anterior segment and fundus
      evaluation, and VA retesting with refractive correction. The prevalence and
      etiology of decreased VA were determined, for both presenting and best-measured
      VA, and better eye and worse eye. MAIN OUTCOME MEASURES: Prevalence of decreased
      presenting and best-measured VA with an identifiable ophthalmic etiology.
      RESULTS: Presenting VA was assessed in 3207 children and best-measured VA in 3364
      children. Although nearly one third of cases of worse-eye decreased presenting VA
      were without an identifiable ophthalmic etiology, this proportion decreased with
      increasing age. Decreased presenting VA that resolved with retesting and was
      associated with uncorrected refractive error was present in the worse eye of 4.3%
      of African-American children and 5.3% of Hispanic children, and in the better eye
      of 1.9% of African-American children and 1.7% of Hispanic children. Decreased
      best-measured VA that was not immediately correctable with spectacles and that
      was because of ocular disease, unilateral or bilateral amblyopia, or probable
      bilateral ametropic amblyopia, was seen in the worse eye of 1.5% of African
      American and 1.9% of Hispanic children, and in the better eye of 0.8% of African
      American and 0.6% of Hispanic children. Amblyopia related to refractive error was
      the most common cause. CONCLUSIONS: More than 5% of African-American and Hispanic
      preschool children in Los Angeles County have either correctable visual
      impairment from uncorrected refractive error or visual impairment from amblyopia
      related to refractive error.

PMID- 19592108
TI  - Brimonidine tartrate 0.15%, dorzolamide hydrochloride 2%, and brinzolamide 1%
      compared as adjunctive therapy to prostaglandin analogs.
AB  - OBJECTIVE: To compare the efficacy of brimonidine, dorzolamide, and brinzolamide
      in reducing intraocular pressure (IOP) when used as adjunctive therapy to a
      prostaglandin analog (PGA). DESIGN: Randomized, controlled, investigator-masked,
      single-site, parallel-group clinical trial. PARTICIPANTS: One hundred twenty eyes
      of 120 patients with open-angle glaucoma or ocular hypertension who had
      inadequate IOP control after at least 6 weeks of monotherapy with a once-daily
      PGA (bimatoprost, latanoprost, or travoprost). INTERVENTION: Study eyes were
      assigned randomly to adjunctive treatment with thrice-daily brimonidine tartrate
      0.15% (n = 41), dorzolamide hydrochloride 2% (n = 40), or brinzolamide 1% (n =
      39) for 4 months. MAIN OUTCOME MEASURES: Efficacy was evaluated by IOP measured
      at 10 am and 4 pm at baseline, month 1, and month 4. RESULTS: The mean IOP at
      each hour at PGA-treated baseline was comparable among treatment groups. After
      initiation of adjunctive therapy, the mean IOP was lower and the mean change from
      baseline IOP was greater in the brimonidine group than in either the dorzolamide
      group or the brinzolamide group at 10 am and 4 pm at months 1 and 4 (P<0.001).
      After 4 months of adjunctive treatment, the mean IOP reduction from baseline at
      10 am and 4 pm was 4.8 mmHg (21%) and 3.8 mmHg (19%) with brimonidine, 3.4 mmHg
      (16%) and 2.8 mmHg (14%) with dorzolamide, and 3.4 mmHg (16%) and 2.6 mmHg (13%)
      with brinzolamide (P<0.001 for brimonidine vs. dorzolamide and brinzolamide at
      each time point). Each of the study drugs was well tolerated, and all patients
      completed the study. CONCLUSIONS: The addition of brimonidine to a PGA provided
      greater IOP lowering than the addition of either dorzolamide or brinzolamide.
      Further studies are needed to evaluate the relative long-term efficacy and
      tolerability of these medications as adjunctive therapy to a PGA. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 19592109
TI  - Assessment of artifacts and reproducibility across spectral- and time-domain
      optical coherence tomography devices.
AB  - PURPOSE: To report the frequency of optical coherence tomography (OCT) scan
      artifacts and to compare macular thickness measurements, interscan
      reproducibility, and interdevice agreeability across 3 spectral-domain (SD) OCT
      (also known as Fourier domain; Cirrus HD-OCT, RTVue-100, and Topcon 3D-OCT 1000)
      devices and 1 time-domain (TD) OCT (Stratus OCT) device. DESIGN: Prospective,
      noncomparative, noninterventional case series. PARTICIPANTS: Fifty-two patients
      seen at the New England Eye Center, Tufts Medical Center Retina Service, between
      February and August 2008. METHODS: Two scans were performed for each of the SD
      OCT protocols: Cirrus macular cube 512 x 128 (software version 3.0; Carl Zeiss
      Meditec, Inc., Dublin, CA), RTVue (E)MM5 and MM6 (software version 3.5; Optovue,
      Inc., Fremont, CA), Topcon 3D Macular and Radial (software version 2.12; Topcon,
      Inc., Paramus, NJ), in addition to 1 TD OCT scan via Stratus macular thickness
      protocol (software version 4.0; Carl Zeiss Meditec, Inc.). Scans were inspected
      for 6 types of OCT scan artifacts and were analyzed. Interscan reproducibility
      and interdevice agreeability were assessed by intraclass correlation coefficients
      (ICCs) and Bland-Altman plots, respectively. MAIN OUTCOME MEASURES: Optical
      coherence tomography image artifacts, macular thickness, reproducibility, and
      agreeability. RESULTS: Time-domain OCT scans contained a significantly higher
      percentage of clinically significant improper central foveal thickness (IFT)
      after manual correction (11-mum change or more) compared with SD OCT scans.
      Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT
      (11.1%) compared with the other SD OCT devices (Topcon 3D, 20.4%; Topcon Radial,
      29.6%; RTVue (E)MM5, 42.6%; RTVue MM6, 24.1%; P = 0.001). All 3 SD OCT devices
      had central foveal subfield thicknesses that were significantly more than that of
      TD OCT after manual correction (P<0.0001). All 3 SD OCT devices demonstrated a
      high degree of reproducibility in the central foveal region (ICCs, 0.92-0.97).
      Bland-Altman plots showed low agreeability between TD and SD OCT scans.
      CONCLUSIONS: Out of all OCT devices analyzed, cirrus HD-OCT scans exhibited the
      lowest occurrence of any artifacts (68.5%), IFT (40.7%), and clinically
      significant IFT (11.1%), whereas Stratus OCT scans exhibited the highest
      occurrence of clinically significant IFT. Further work on improving segmentation
      algorithm to decrease artifacts is warranted.

PMID- 19592111
TI  - Acute retinal necrosis: clinical features, early vitrectomy, and outcomes.
AB  - OBJECTIVE: To determine the viral diagnosis and the outcome of eyes with acute
      retinal necrosis (ARN) treated with intravenous acyclovir and oral prednisolone
      alone or combined with early vitrectomy and intravitreal acyclovir lavage.
      DESIGN: Nonrandomized, retrospective, interventional, comparative, consecutive
      series. PARTICIPANTS: A cohort of 27 human immunodeficiency virus-negative
      patients with ARN comprising 24 unilateral and 3 bilateral cases. INTERVENTION:
      Vitreous biopsy for viral diagnosis. Twenty eyes were treated with intravenous
      acyclovir in combination with oral prednisolone (group A). Ten eyes were treated
      additionally with early vitrectomy, intravitreal acyclovir lavage, laser
      demarcation of necrotic retinal areas when feasible-with or without scleral
      buckling, and gas or silicone oil tamponade (group B). Vitrectomy was performed
      in all cases of secondary rhegmatogenous retinal detachment (RD). MAIN OUTCOME
      MEASURES: Results of vitreous biopsy, rate of RD, rate of phthisis bulbi, and
      course of best-corrected visual acuity (BCVA). RESULTS: Varicella zoster virus
      (VZV) was detected in 26 eyes, followed by herpes simplex virus (5 eyes), and
      Epstein-Barr virus (2 eyes, in conjunction with VZV). An RD developed in more
      eyes in group A (18 of 20 eyes) than in group B (4 of 10 eyes; P = 0.007). In 2
      of 20 eyes in group A and in 0 of 10 eyes in group B, phthisis bulbi developed
      without a significant difference between groups A and B. Mean BCVA (logarithm of
      the minimum angle of resolution) at first visit was 1.09 (standard deviation
      [SD], 0.83), and mean final BCVA was 1.46 (SD, 0.88) without significant
      difference between groups A and B. CONCLUSIONS: Varicella zoster virus is the
      leading cause of ARN. Visual prognosis is guarded. Early vitrectomy with
      intravitreal acyclovir lavage was associated with a lower incidence of secondary
      RD; however, it did not improve mean final visual acuity.

PMID- 19592110
TI  - Driving cessation and driving limitation in glaucoma: the Salisbury Eye
      Evaluation Project.
AB  - OBJECTIVE: To determine if glaucoma is associated with driving limitation or
      cessation. DESIGN: Cross-sectional analysis within a longitudinal, population
      based cohort study. PARTICIPANTS AND CONTROLS: One thousand one hundred thirty
      five ever-drivers between 73 and 93, including 70 subjects with unilateral and 68
      subjects with bilateral glaucoma. METHODS: All subjects reported their driving
      habits during each of 4 study rounds. During the fourth and final study round,
      subjects were assessed systematically for the presence of glaucoma. MAIN OUTCOME
      MEASURES: Self-reported driving cessation or driving limitation, including
      cessation of night driving, driving fewer than 3000 miles annually, or cessation
      of driving in unfamiliar areas. RESULTS: Fifteen percent of subjects without
      glaucoma no longer were driving at the end of the cohort study, compared with 21%
      of unilateral glaucoma subjects (P = 0.2) and 41% of bilateral glaucoma subjects
      (P<0.001). Multivariate regression analysis showed that bilateral (odds ratio
      [OR], 2.6; P = 0.002), but not unilateral (OR, 1.5; P = 0.3), glaucoma subjects
      were more likely no longer to be driving when compared with subjects without
      glaucoma. The odds that bilateral glaucoma subjects no longer were driving
      doubled for every 5 dB of visual field (VF) worsening in the better eye
      (P<0.001). Driving cessation within the previous 2 years was analyzed using
      separate multiple regression models, and both bilateral (OR, 3.6; P = 0.004) and
      unilateral (OR, 2.4; P = 0.06) glaucoma subjects were more likely to stop driving
      over this period than subjects without glaucoma. Driving cessation associated
      with bilateral glaucoma was present in 0.82% of the population, or 1 in every 122
      individuals. Greater numbers of driving limitations were not more likely among
      subjects with glaucoma than subjects without glaucoma. However, bilateral
      glaucoma subjects did attribute more driving limitations to difficulties with
      their vision than subjects without glaucoma (OR, 2.2; P = 0.02). CONCLUSIONS:
      Bilateral, and possibly unilateral, glaucoma is associated with significantly
      higher rates of driving cessation among the elderly. The substantial difference
      in driving patterns seen with different degrees of better-eye VF damage suggests
      that minimizing VF loss in the better-seeing eye is associated with better
      functional outcomes.

PMID- 19592112
TI  - Reaction of nitric oxide with the oxidized di-heme and heme-copper oxygen
      reducing centers of terminal oxidases: Different reaction pathways and end
      products.
AB  - Inhibition of terminal oxidases by nitric oxide (NO) has been extensively
      investigated as it plays a role in regulation of cellular respiration and
      pathophysiology. Cytochrome bd is a tri-heme (b(558), b(595), d) bacterial
      oxidase containing no copper that couples electron transfer from quinol to O(2)
      (to produce H(2)O) with generation of a transmembrane protonmotive force. In this
      work, we investigated by stopped-flow absorption spectroscopy the reaction of NO
      with Escherichia coli cytochrome bd in the fully oxidized (O) state. We show that
      under anaerobic conditions, the O state of the enzyme binds NO at heme d with
      second-order rate constant k(on)=1.5+/-0.2x10(2) M(-1) s(-1), yielding a nitrosyl
      adduct (d(3+)-NO or d(2+)-NO(+)) with characteristic optical features (an
      absorption increase at 639nm and a red shift of the Soret band). The reaction
      mechanism is remarkably different from that of O cytochrome c oxidase in which
      the heme-copper binuclear center reacts with NO approximately three orders of
      magnitude faster, forming nitrite. The data allow us to conclude that in the
      reaction of NO with terminal oxidases in the O state, Cu(B) is indispensable for
      rapid oxidation of NO into nitrite.

PMID- 19592113
TI  - The clinical efficacy of fluoroquinolone and macrolide combination therapy
      compared with single-agent therapy against community-acquired pneumonia caused by
      Legionella pneumophila.

PMID- 19592114
TI  - Widespread public misconception in the early phase of the H1N1 influenza
      epidemic.
AB  - OBJECTIVES: To investigate the community responses and preparedness for a
      possible epidemic of H1N1 influenza in Hong Kong shortly after an imported case
      was confirmed. METHODS: A random sample of 550 Chinese adults in the Hong Kong
      general population was interviewed during May 7-9, 2009. RESULTS: The public did
      not perceive a high likelihood of having a local H1N1 outbreak, nor did they
      regard H1N1 as a threatening disease. Frequent hand-washing (73.6%) and use of
      face-masks in case of flu symptoms (47.9%) were prevalent. The public approved of
      governmental policies including the quarantining of hotel guests, was not
      panicking and perceived a high self-efficacy of self-protection. However,
      misconceptions were prevalent and the public avoided visiting crowded places
      (9.3%), which many people wrongly believed was a government recommendation.
      CONCLUSION: Although the public response demonstrated vigilance and preparedness
      there were signs of complacency. Clear communication, updated scientific
      information and transparency on government decision making are warranted. Data of
      the study provide a baseline for an ongoing surveillance program to help shape
      policy and provide information to the international community.

PMID- 19592116
TI  - Monitoring treatment response and outcomes using the World Health Organization's
      Wellbeing Index in psychiatric care.
AB  - BACKGROUND: Effective psychiatric care requires reliable measurement of patient
      progress and outcome. The current study aimed to assess the clinical validity of
      the WHO Wellbeing Index (WHO-5; Bech, P., Gudex, C., Johansen, K.S., 1996. The
      WHO (Ten) Wellbeing Index: validation in diabetes. Psychotherapy and
      Psychosomatics 65, 183-190.) for use as a measure of individual treatment
      response and outcome in mental health care. METHOD: Three hundred and eighteen
      consecutive inpatients and day patients at an Australian private psychiatric
      facility completed the WHO-5, SF-36 and DASS-21 routinely during treatment, and
      152 undergraduate students completed the WH0-5. RESULTS: The WHO-5 was shown to
      be a measure with high reliability, validity and sensitivity to change, for use
      with patients who have affective or neurotic primary diagnoses. Further to this,
      regression analyses demonstrated that early scores on the measure predicted final
      outcome. Criteria for clinically significant recovery are also presented.
      LIMITATIONS: The results may be generalized to samples with primary diagnoses of
      affective and anxiety disorders. Assessment of the WHO-5 as a measure of
      treatment response is warranted in other patient samples. CONCLUSIONS: The
      current findings illustrate the potential of the WHO-5 as a quick, reliable and
      valid means for assessing patient outcome and monitoring patient response to
      treatment in psychiatric services.

PMID- 19592117
TI  - Airway procedures and hemangiomas: treatment patterns and outcome in U.S.
      pediatric hospitals.
AB  - OBJECTIVE: Characterize and compare care in children with hemangiomas, who do or
      do not undergo airway procedures. METHODS: National retrospective cohort study of
      patients aged 0-18 with hemangiomas, from 33 freestanding United States pediatric
      hospital discharge records, 2001-2005. The main outcome measures were therapy,
      readmission and mortality. RESULTS: Of 2890 patients diagnosed with hemangiomas,
      337 (12%) underwent airway procedures. Most airway procedures were for patients
      between ages 1 and 11 months. Patients with hemangiomas and airway procedures had
      more steroid use (80%), increased readmission (30%), and increased mortality (2%)
      compared to hemangioma patients without airway procedures. Procedures (i.e.
      laser, open surgery, tracheotomy) and age over 4 months in airway procedure
      patients were associated with decreased readmission. Increased readmissions were
      associated with systemic steroid administration. CONCLUSION: Hemangioma patients
      who undergo airway procedures experience increased medical and surgical therapy
      compared to those who do not. Readmission is increased in patients with
      hemangiomas and airway procedures, but surgical intervention and age greater than
      4 months decreased readmission.

PMID- 19592115
TI  - Iron deficiency anemia in infancy and reach and grasp development.
AB  - This study assessed 9 kinematic characteristics of infants' reach and grasp to
      test the hypothesis that iron deficiency anemia (IDA) delays upper extremity
      motor development. Reach and grasp movements, recorded with a 3D-motion capture
      system, were compared in 9- to 10-month-old infants (4 IDA vs. 5 iron-sufficient
      [IS]). Based on normative motor development data available for 6 characteristics,
      the results indicated poorer upper extremity control in IDA infants: 2
      characteristics showed statistically significant group differences despite small
      n, and the other 4 had strong indications for such results (effect sizes [Cohen's
      d]>1.2). The remaining 3 measures, for which normative studies do not show
      developmental changes in this age period, showed significant or moderate-to-large
      effect differences. Poorer upper-extremity control in IDA infants in the short
      term in this study and in the long-term despite iron therapy in other studies
      suggests that a motor intervention may be warranted when IDA is detected in
      infancy.

PMID- 19592118
TI  - Facial nerve mapping and monitoring in lymphatic malformation surgery.
AB  - OBJECTIVE: Establish the efficacy of preoperative facial nerve mapping and
      continuous intraoperative EMG monitoring in protecting the facial nerve during
      resection of cervicofacial lymphatic malformations. METHODS: Retrospective study
      in which patients were clinically followed for at least 6 months postoperatively,
      and long-term outcome was evaluated. Patient demographics, lesion characteristics
      (i.e., size, stage, location) were recorded. Operative notes revealed surgical
      techniques, findings, and complications. Preoperative, short-/long-term
      postoperative facial nerve function was standardized using the House-Brackmann
      Classification. Mapping was done prior to incision by percutaneously stimulating
      the facial nerve and its branches and recording the motor responses.
      Intraoperative monitoring and mapping were accomplished using a four-channel,
      free-running EMG. Neurophysiologists continuously monitored EMG responses and
      blindly analyzed intraoperative findings and final EMG interpretations for
      abnormalities. RESULTS: Seven patients collectively underwent 8 lymphatic
      malformation surgeries. Median age was 30 months (2-105 months). Lymphatic
      malformation diagnosis was recorded in 6/8 surgeries. Facial nerve function was
      House-Brackmann grade I in 8/8 cases preoperatively. Facial nerve was abnormally
      elongated in 1/8 cases. EMG monitoring recorded abnormal activity in 4/8 cases-
      two suggesting facial nerve irritation, and two with possible facial nerve
      damage. Transient or long-term facial nerve paresis occurred in 1/8 cases (House
      Brackmann grade II). CONCLUSIONS: Preoperative facial nerve mapping combined with
      continuous intraoperative EMG and mapping is a successful method of identifying
      the facial nerve course and protecting it from injury during resection of
      cervicofacial lymphatic malformations involving the facial nerve.

PMID- 19592119
TI  - Diagnostic accuracy meta-analysis: a review of the basic principles of
      interpretation and application.
AB  - Evidence-based practice has become increasingly important in all aspects of
      medicine. The availability and variety of diagnostic tests in cardiovascular
      practice are increasing rapidly and are therefore under scrutiny in the
      literature. Diagnostic meta-analysis is used to summarise and combine results
      from multiple studies. The analytical techniques for diagnostic meta-analysis
      differ from other meta-analyses because the measures of diagnostic accuracy
      (sensitivity and specificity) are unique to diagnostics. However, the benchmark
      for diagnostic meta-analysis techniques continues to move forward, making
      interpretation and application of the results difficult for clinicians. This
      article explains the terminology of the current standards in diagnostic meta
      analysis, and outlines the principles of applying these results to clinical
      practice.

PMID- 19592120
TI  - Gender and age-dependent differences in the bradykinin-degradation within the
      pericardial fluid of patients with coronary artery disease.
AB  - Cardiovascular diseases (CVD) and, in particular, coronary artery disease (CAD)
      are the leading causes of death in developed countries, especially in the elderly
      population. Males exhibit a higher risk for cardiovascular events than women. The
      pericardial fluid (PF) is in direct contact with the epicardial sections of the
      coronary arteries and the perimyocardium. A systematic analysis of gender
      specific or age-related differences in angiotensin-related pathways like
      bradykinin metabolism however, has not been performed in the PF so far.
      Therefore, the amounts of angiotensin-converting enzyme (ACE) and the rate of the
      degradation of bradykinin (BK) and the amounts/activity of major BK-degrading
      enzymes, aminopeptidase N (APN) and dipeptidyl-aminopeptidase IV (DPIV), were
      assessed in the pericardial fluid (PF) of 44 patients undergoing coronary artery
      bypass grafting. We found BK being degraded within the PF. Interestingly, there
      was an age-dependent decrease in the amounts of ACE protein in women. In elderly
      women, ACE/APN and ACE/DPIV ratios were substantially reduced to 41.4% or 29.4%
      respectively (p<0.05). In contrast, an age-dependent decline of ACE protein and
      ACE/protease ratios were not found in men. In men and women, total BK degradation
      correlated with age (r=0.5; p=0.021) further supporting a switch in BK
      metabolising enzymes in elderly women. Thus, we can show age- and gender
      dependent differences in BK metabolism within the PF in patients with coronary
      artery disease. The present finding that the expression of ACE is lowest in
      elderly women, despite the presence of similar BK degradation, might help to
      explain the potentially reduced therapeutic effects of ACE inhibitors in elderly
      women.

PMID- 19592121
TI  - Promoting creativity and innovation in biotechnology.

PMID- 19592123
TI  - Dosimetric characteristics of 6 and 10MV unflattened photon beams.
AB  - PURPOSE: To determine dosimetric properties of unflattened megavoltage photon
      beams. MATERIALS AND METHODS: Dosimetric data including depth dose, profiles,
      output factors and phantom scatter factors from three different beam qualities
      provided by Elekta Precise linacs, operated with and without flattening filter
      were examined. Additional measurements of leaf transmission, leakage radiation
      and surface dose were performed. In flattening filter free (FFF) mode a 6-mm
      thick copper filter was placed into the beam to stabilize it. RESULTS: Depths of
      dose maxima for flattened and unflattened beams did not deviate by more than 2mm
      and penumbral widths agreed within 1mm. In FFF mode the collimator exchange
      effect was found to be on average 0.3% for rectangular fields. Between maximum
      and minimum field size head scatter factors of unflattened beams showed on
      average 40% and 56% less variation for 6 and 10MV beams than conventional beams.
      Phantom scatter factors for FFF beams differed up to 4% from the published
      reference data. For field sizes smaller than 15cm, surface doses relative to the
      dose at d(max) increased for unflattened beams with maximum differences of 7% at
      6MV and 25% at 10MV for a 5x5cm(2) field. For a 30x30cm(2) field, relative
      surface dose decreased by about 10% for FFF beams. Leaf transmission on the
      central axis was 0.3% and 0.4% lower for unflattened 6 and 10MV beams,
      respectively. Leakage radiation was reduced by 52% for 6MV and by 65% for 10MV
      unflattened beams. CONCLUSIONS: The results of the study were independently
      confirmed at two radiotherapy centres. Phantom scatter reference data need to be
      reconsidered for medical accelerators operated without a flattening filter.

PMID- 19592124
TI  - Associations of the CTLA-4 polymorphisms with type 1 diabetes in a Chilean
      population: case-parent design.
AB  - CTLA-4 plays a key role in T cells regulation. We analysed the CTLA-4 +49A/G and 
      318C/T polymorphisms in 178 cases of type 1 diabetes and their parents (534
      individuals) from Santiago, Chile. A significant overall association with T1D
      (p=0.028) was observed, possibly due to an overtransmission of the G-T haplotype.

PMID- 19592125
TI  - Educational attainment and effectiveness of lifestyle intervention in the Finnish
      Diabetes Prevention Study.
AB  - We used data from the Finnish Diabetes Prevention Study to analyze the
      effectiveness of lifestyle intervention according to educational attainment. The
      effect of intervention on lifestyle changes and diabetes incidence was
      independent of education. The prevention of type 2 diabetes by lifestyle
      intervention is effective regardless of participants' educational attainment.

PMID- 19592122
TI  - Role of image-guided patient repositioning and online planning in localized
      prostate cancer IMRT.
AB  - PURPOSE: To determine the expected benefit of image-guided online replanning over
      image-guided repositioning of localized prostate cancer intensity-modulated
      radiotherapy (IMRT). MATERIALS AND METHODS: On 10 to 11 CT scans of each of 10
      early-stage prostate cancer patients, the prostate, bladder and rectum are
      manually segmented. Using a 3-mm PTV margin expansion from the CTV, an IMRT plan
      is made on the first CT scan of each patient. Online repositioning is simulated
      by recalculating the IMRT plan from the initial CT scan on the subsequent CT
      scans of each patient. For online replanning, IMRT is replanned twice on all CT
      scans, using 0-mm and 3-mm margins. The doses from subsequent CT images of each
      patient are then deformed to the initial CT anatomy using a mesh-based thin-plate
      B-spline deformation method and are accumulated for DVH and isodose review.
      RESULTS: Paired t-tests show that online replanning with 3-mm margins
      significantly increases the prostate volume receiving the prescribed dose over
      replanning with 0-mm margins (p-value 0.004); gives marginally better target
      coverage than repositioning with 3-mm margins(p-value 0.06-0.343), and reduces
      variations in target coverage over repositioning. Fractional volumes of rectum
      and bladder receiving 75%, 80%, 85%, 90%, and 95% (V75, V80, V85, V90, and V95)
      of the prescription dose are evaluated. V90 and V95 values for the rectum are
      1.6% and 0.7 % for 3-mm margin replanning and 1% and 0.4 % for 0-mm margin
      replanning, with p-values of 0.010-0.011. No significant differences between
      repositioning and replanning with 3-mm margins are found for both the rectum and
      the bladder. CONCLUSIONS: Image-guided replanning using 3-mm margins reduces
      target coverage variations, and maintains comparable rectum and bladder sparing
      to patient repositioning in localized prostate cancer IMRT. Marginal reductions
      in doses to rectum and bladder are possible when planning margins are eliminated
      in the online replanning scenario. However, further reduction in treatment
      planning margins is not recommended.

PMID- 19592126
TI  - Show me your signaling--and I'll tell you who you are.

PMID- 19592127
TI  - Can upfront systemic chemotherapy replace stereotactic radiosurgery or whole
      brain radiotherapy in the treatment of non-small cell lung cancer patients with
      asymptomatic brain metastases?
AB  - BACKGROUND: The optimal treatment for non-small cell lung cancer (NSCLC) patients
      with asymptomatic brain metastasis is still controversial. This study aimed to
      analyze the outcome for various treatment modalities including chemotherapy only,
      upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in
      NSCLC patients with asymptomatic brain metastases. METHODS: We retrospectively
      reviewed the medical records of patients with histopathologically proven NSCLC
      and synchronous asymptomatic brain metastasis between January 2003 and December
      2007. RESULTS: From the database, 741 NSCLC patients were identified to have been
      diagnosed of brain metastases during initial staging or follow-up between January
      2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were
      identified to have synchronous brain metastasis without associated symptoms. Of
      the 129 patients included in the analysis, 78 (57.8%) patients received systemic
      chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24
      (17.8%) patients received upfront SRS and chemotherapy. There was no significant
      difference in overall survival among three groups (systemic chemotherapy alone,
      13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT
      followed by chemotherapy, 17.7 months, respectively; P=0.86). Subset analysis of
      110 adenocarcinoma patients showed that the median OS for patients treated with
      upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7
      months; P=0.01) or chemotherapy alone (29.3 months versus 14.6 months; P=0.04).
      CONCLUSION: This study suggested a potential role of systemic chemotherapy alone
      or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment
      of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal
      treatment modality, however, needs to be defined in prospective trials for this
      subset of patients.

PMID- 19592128
TI  - Polyreactive antibodies in multidonor-derived immunoglobulin G: theory and
      conclusions drawn from experiments.
AB  - Multidonor-derived (md) preparations of IgG antibodies, agents of therapeutic
      potential, contain molecules interacting at clonal concentrations (concns) and
      with affinities recently estimated to cover a considerable range. Here we
      demonstrate that polyreactivity of the monomeric molecules represents the
      essential driving force of formation of the main reaction product, the IgG
      dimers. This conclusion is obtained by applying the principles of the law of mass
      action to dimer formation by polyreactive monomeric reactants. In addition,
      general interrelationships involving the mean number of reactants per reactor,
      the experimental dimer portion (w/w) and the mean concentrations of monomers in a
      polyreactive and monoreactive antibody system are derived. These
      interrelationships, together with quantitative results obtained from simplified
      computational kinetic models of polyreactive antibodies, allow to estimate a
      remarkably high value for the mean number of reactants per reactor, exceeding 60
      for the underlying IgG preparation obtained from pooled human plasma units of
      5000 donors. Moreover, the potential origin and other consequences of
      polyreactivity are outlined.

PMID- 19592129
TI  - Inflammatory biomarker, neopterin, predominantly enhances myelopoiesis, which
      suppresses erythropoiesis via activated stromal cells.
AB  - Neopterin is produced by monocytes and is a useful biomarker for inflammation. We
      found previously that neopterin enhanced myelopoiesis but suppressed B
      lymphopoiesis triggered by the positive and negative regulations of cytokines
      produced by stromal cells in mice. The effects of neopterin on erythropoiesis
      during the enhancement of myelopoiesis were determined in the present study using
      C57BL/6J mice. The intravenous injection of neopterin into mice resulted in a
      prolonged decrease in the number of femoral erythroid progenitor cells (BFU-Es
      and CFU-Es), whereas the number of femoral myeloid progenitor cells (CFU-GMs) was
      increased. Interestingly, the oscillatory changes in the number of erythroid
      progenitor cells were reciprocal to those of myeloid progenitor cells. The
      expression of Cdc42, a regulator of the balance between erythropoiesis and
      myelopoiesis, was down-regulated, implying that the suppression of erythropoiesis
      is due to myelopoietic predominance. Furthermore, the expression of SDF-1 in
      stromal cells, a negative regulator of erythropoiesis, was up-regulated. These
      results suggest that neopterin facilitates myelopoiesis in the bone marrow by
      suppressing erythropoiesis, thereby contributing to the potential up-regulation
      of inflammatory process.

PMID- 19592130
TI  - The CD300 molecules regulate monocyte and dendritic cell functions.
AB  - The CD300 glycoproteins are a family of related leucocyte surface molecules that
      modulate a diverse array of cell processes via their paired triggering and
      inhibitory receptor functions. All family members have a single Ig-V like domain
      and they share a common evolutionary pathway. At least one member of the family
      has undergone significant positive selection (ranked second in the top 50)
      indicating a need to maintain some crucial function. Here we have reviewed the
      CD300 family members, and their expression on cells of the monocyte and dendritic
      cell lineages. The consequences of CD300 molecule expression by these leucocyte
      lineages are only now beginning to be understood. The ability to fine tune
      monocyte and dendritic cell function and immune responses highlights several
      potential options to exploit these molecules as therapeutic targets in chronic
      inflammatory diseases, allergy and other disease states.

PMID- 19592131
TI  - Live imaging reveals that the Drosophila actin-binding ERM protein, moesin, co
      localizes with the mitotic spindle.
AB  - Members of the vertebrate ezrin-radixin-moesin (ERM) protein family crosslink the
      actin cytoskeleton and the cell membrane and are, therefore, considered
      cytoplasmic regulators of cell adhesion, cell movement and membrane trafficking.
      Here we demonstrate that besides its cytoplasmic functions Drosophila moesin, the
      only ERM protein in Drosophila melanogaster, exhibits a dynamic cell cycle
      dependent nuclear localization. In a small fraction of cells and at a low level,
      moesin can be detected in interphase nuclei in regions complementary to the
      chromatin; its level rapidly increases during prophase and it co-localizes with
      the actin network surrounding the mitotic spindles throughout mitosis. We also
      found that the predicted single nuclear localization signal in moesin is not
      necessary for the nuclear accumulation of the protein. FRAP experiments confirmed
      this finding and further revealed that the mitotic localization of moesin is
      highly dynamic. Immuno-histochemical staining for moesin demonstrated the
      existence of spindle association in wild-type embryos. The biological relevance
      of this phenomenon is indicated by the mitotic phenotypes detected in S2 cells
      treated with moesin RNAi, and awaits future exploration.

PMID- 19592132
TI  - Induction of ethylene in avocado fruit in response to chilling stress on tree.
AB  - Chilling of avocado fruit (Persea americana cv. Arad) in the orchard caused a
      dramatic induction of fruit ripening and a parallel increase in ethylene
      biosynthesis and receptor genes' expression during shelf life. In-orchard
      chilling stress stimulated ethylene and CO(2) production already in fruit
      attached to the tree, and these reduced thereafter during 20 degrees C storage.
      In non-chilled control fruit, ethylene and CO(2) production started after 3d at
      20 degrees C and exhibited a climacteric peak. In-orchard chilling stress also
      led to membrane destruction expressed as higher electrical conductivity (EC) in
      chilling stressed (CS) fruit and accelerated softening compared with control
      fruit. The increase in ethylene production on the day of harvest in CS fruit was
      accompanied by high expression of two 1-aminocyclopropane-1-carboxylic aCSd (ACC)
      synthase genes: PaACS1 and PaACS2, and ACC oxidase PaACO. The initial gene
      expressions of PaACS1, PaACS2, and PaACO in the CS fruit at the day of harvest
      was similar to the levels reached by the control fruit after 4d at 20 degrees C.
      The expression levels of both PaETR and PaERS1 in CS fruit on tree were 25 times
      higher than the control. In control fruit, expression of ethylene receptor genes
      was very low at harvest and increased in parallel to the onset of the climacteric
      ethylene peak. PaCTR1 transcript levels were less affected by chilling stress,
      and small changes (less than 3-fold) were observed in CS fruit on the day of
      harvest. Together, our results suggest that ethylene biosynthesis and ethylene
      response-pathway genes are involved in regulation of ethylene responsiveness in
      response to in-orchard chilling stress and during ripening.

PMID- 19592133
TI  - Regulation of resistance and susceptibility in wheat-powdery mildew pathosystem
      with exogenous cytokinins.
AB  - Dose-response relationship between resistance of wheat seedlings (Triticum
      aestivum, cultivar Zarya) to Erysiphe graminis f. sp. tritici Marchal. (Syn.
      Blumeria graminis), a causal organism of wheat powdery mildew and exogenous
      zeatin has been investigated. Two-week-old seedlings were inoculated with the
      pathogen. Zeatin or zeatinriboside were added to the nutrient solution
      immediately after inoculation. The dose-response curve of cytokinin in the most
      cases was multiphasic, with peaks of increased susceptibility occurring at 0.25
      1.5 and 1.5-9microM cytokinin, separated by a region of increased resistance at
      0.5-3microM cytokinin. The change in mineral nutrition or simultaneous treatment
      with thidiazuron revealed alterations of the dose-response curve ranging from a
      curve with maximum of resistance to a curve with maximum of susceptibility. Both
      multiphase nature of dose-response and its variability were proposed as possible
      explanations for earlier observed discrepancies in experimental data on
      modification of disease resistance by cytokinins. A mathematical model for two
      metabolic processes with substrate inhibition connected in-series was suggested
      to explain the multiphase dose-response. In this model, the product of the first
      reaction was used as substrate for the second reaction. Numerical experiments
      showed the changes in the shape of dose-response curve with changes in parameters
      dependent of cytokinin metabolism.

PMID- 19592134
TI  - Adaptation of the obligate CAM plant Clusia alata to light stress: Metabolic
      responses.
AB  - In the Crassulacean acid metabolism (CAM) plants Clusia alata Triana and Planch.,
      decarboxylation of citrate during phase III of CAM took place later than malate
      decarboxylation. The interdependence of these two CO(2) and NADPH sources is
      discussed. High light accelerated malate decarboxylation during the day and
      lowered citrate levels. Strong light stress also activated mechanisms that can
      protect the plant against oxidative stress. Upon transfer from low light
      (200micromol m(-2)s(-1)) to high light (650-740micromol m(-2)s(-1)), after 2
      days, there was a transient increase of non-photochemical quenching (NPQ) of
      fluorescence of chlorophyll a of photosystem II. This indicated acute
      photoinhibition, which declined again after 7 days of exposure. Conversely, after
      1 week exposure to high light, the mechanisms of interconversion of violaxanthin
      (V), antheraxanthin (A), zeaxanthin (Z) (epoxydation/de-epoxydation) were
      activated. This was accompanied by an increase in pigment levels at dawn and
      dusk.

PMID- 19592136
TI  - Incidence and risk factors for surgical site infection after simultaneous
      pancreas-kidney transplantation.
AB  - A simultaneous pancreas-kidney transplantation (SPKT) is the best treatment
      option for type I diabetic patients with advanced chronic renal failure.
      Infectious complications affect 7-50% of the patients receiving this procedure.
      We conducted a nested case-control study to assess the risk factors for surgical
      site infection (SSI) in patients receiving SPKT at our centre between 2000 and
      2006. Of the 119 evaluated transplant recipients, 55 (46.2%) developed SSIs and
      the 30 day mortality was 11.8%. Gram-negative organisms were the predominant
      organisms isolated from SSIs. After multivariate logistic regression, the
      variables independently associated with SSI were: acute tubular necrosis, post
      transplant fistula and graft rejection. This study demonstrated a high incidence
      of SSI in this patient cohort and variables related to the surgical procedure
      were closely associated with the development of SSI.

PMID- 19592135
TI  - [Interferon-related retinopathy in a man with chronic hepatitis C].
AB  - A 50-year-old diabetic man receiving insulin, and suffering from chronic
      hepatitis C treated with interferon alfa and ribavirin presented with an acute
      peripheral scotoma and retinopathy associated with interferon therapy. When the
      treatment was interrupted, all the clinical symptoms and the test abnormalities
      returned to normal. If the association of interferon alpha and ribavirin increase
      the incidence of retinopathy, diabetes, and hypertension are also risk factors.
      Therapeutic abstention and monitoring are usual in the absence of visual acuity
      changes. However, in certain cases, such as in this patient, ceasing treatment as
      a matter of urgency avoids serious visual aftereffects. However, because of the
      incidence on the liver disease, this treatment interruption requires having
      clearly ruled out all other differential diagnoses.

PMID- 19592137
TI  - Successful control of norovirus outbreak in an infirmary with the use of alcohol
      based hand rub.

PMID- 19592138
TI  - Review of Lancet conference on healthcare-associated infections.

PMID- 19592139
TI  - Audit of the antimicrobial treatment of Clostridium difficile toxin-positive
      episodes using an integrated electronic prescribing, information and
      communication system.

PMID- 19592140
TI  - [Barthel and Charlson indexes for the prognosis of mortality and
      institutionalization in hospitalized geriatric patients].
AB  - INTRODUCTION: To compare the validity of the Barthel (BI) and Charlson
      comorbidity index (CCI) as well as the age-adjusted CCI for the prognosis of
      mortality and institutionalization in hospitalized geriatric patients. MATERIAL
      AND METHODS: A retrospective study was conducted to evaluate patients admitted to
      an acute care geriatric ward and mid-term care facility in 2006 (n=343). The
      independent variables were the admission BI (registered in the clinical history
      in all patients) and the CCI and the age-adjusted CCI, which were registered "a
      posteriori" using the available information. The outcome variable was mortality
      or institutionalization when the patient was discharged. The sensitivity and
      specificity values for each of the cut-off points selected from the scales
      analyzed were recorded and ROC curves were constructed for each of these points;
      the area under the curve (AUC) with a confidence interval (CI) of up to 95% was
      calculated. RESULTS: The mean age was 82.3 years (58.6% women). The AUC was 0.736
      (95% CI=0.68-0.79) for the BI, 0.61 (95% CI=0.55-0.67) for the CCI and 0.625 (95%
      CI=0.56-0.69) for the age-adjusted CCI. Statistically significant differences
      were found among the AUC of the BI compared with that of the other two indexes
      (p<0.01). CONCLUSIONS: As predictors of mortality and institutionalization, the
      BI was superior to the CCI and the age-adjusted CCI. The BI could therefore be
      more useful than the other two indexes when considering an adequate use of
      healthcare services.

PMID- 19592141
TI  - [Analysis of placement in public nursing homes after hospital admission in the
      fragile elderly].
AB  - INTRODUCTION: To analyze placement in public nursing homes in elderly inpatients
      referred by the social work unit. MATERIAL AND METHODS: We performed a cohort
      study in an acute geriatric unit of a tertiary hospital. The sociodemographic,
      clinical, functional and socioeconomic data registered on admission (inclusion
      period: 4 years) were analyzed. The patients were followed-up for 6 months after
      discharge. The percentage gaining places in public nursing homes, the waiting
      time (monthly incidence rate) and the reasons for not gaining a place were
      evaluated. The variables associated with gaining a place were introduced into a
      multivariate logistic regression model. RESULTS: A total of 415 elders were
      referred to public nursing homes. The mean age was 85.1 years (SD=6.7), and 61.9%
      were women. During the follow-up period, 72 elders were granted a place (17.3%;
      monthly incidence rate 3.14%). In the multivariate analysis, the factors
      independently associated with gaining a place at a public nursing home were
      living alone (OR 2.788; p=0.005), having a lower income (OR 0.807; p=0.018),
      having a social work report from the hospital (OR 2.132; p=0.037), having
      previously requested a place at a public nursing home (OR 3.298; p=0.002) and
      discharge destination other than the home (OR 5.792; p<0.001). The main causes
      associated with not gaining a place were death while on the waiting list (41.4%)
      and not completing the paperwork (32.9%). CONCLUSIONS: Hospitalization in the
      frail elderly frequently leads to requests for public nursing home admission,
      although few places are granted in the short term to patients in the acute unit.
      Certain socioeconomic factors and referral by social workers were positively
      associated with gaining a place. However, the waiting time leads to a substantial
      proportion of deaths and incomplete paperwork, largely due to the complexity of
      the process.

PMID- 19592142
TI  - Bleeding in the heritable connective tissue disorders: mechanisms, diagnosis and
      treatment.
AB  - Easy bruising and bleeding are prominent features of some heritable disorders of
      connective tissue (HDCT), resulting from fragility of capillaries and the
      perivascular connective tissue rather than clotting or platelet dysfunction. The
      bleeding tendency is most prominent in the Ehlers-Danlos syndrome (EDS), a
      heterogeneous group of HDCT sharing clinical manifestations of fragility in skin,
      ligaments, blood vessels and internal organs. Most EDS-subtypes are caused by
      mutations in genes encoding fibrillar collagens type I, III or V, or genes
      encoding enzymes involved in the posttranslational modification of collagens. In
      the vascular subtype of EDS, caused by defects in type III collagen, fragility of
      vessel walls can lead to life-threatening bleeding and premature death. Bleeding
      tendency is also a common feature in other EDS-subtypes, leading to bruising
      either spontaneously or after minimal trauma. This paper reviews the clinical
      aspects of bleeding and bruising in different HDCT and covers diagnostic and
      therapeutic aspects relevant to bleeding in these disorders.

PMID- 19592144
TI  - Evolving statistical methods to facilitate evaluation of the causal association
      between erythropoiesis-stimulating agent dose and mortality in nonexperimental
      research: strengths and limitations.
AB  - Findings from randomized controlled trials examining the efficacy of therapy with
      erythropoiesis-stimulating agents (ESAs) to normalize hemoglobin levels in
      patients with chronic kidney disease or kidney failure have raised questions
      regarding the safety of this class of drugs. However, no trial to date has
      specifically assessed the safety of ESA-dosing algorithms used to achieve the
      lower hemoglobin targets typically using in clinical practice. Although a wealth
      of nonexperimental data is available for dialysis patients, analyses based on
      these data are more susceptible to confounding bias than randomized controlled
      trials. Conducting valid pharmacoepidemiologic studies of drug effects in
      hemodialysis patients is complicated by the extent of their comorbidities,
      frequent hospitalizations, various concomitant medications, and an exceedingly
      high mortality rate. The need for greater ESA doses for the treatment of anemia
      in sicker patients potentially and plausibly generates confounding by indication,
      the control of which is complicated by the presence of time-dependent
      confounding. Here, we describe sources of bias in nonexperimental studies of ESA
      therapy in hemodialysis patients and critically appraise analytical methods that
      may help minimize bias in such studies.

PMID- 19592145
TI  - Prognostic value of kidney function in patients with ST-elevation and non-ST
      elevation acute myocardial infarction treated with percutaneous coronary
      intervention.
AB  - BACKGROUND: Patients with decreased kidney function and acute ST-elevation
      myocardial infarction (STEMI) and non-STEMI are less likely to receive
      reperfusion therapy and aggressive medical treatment. This undertreatment may
      contribute to the poor outcome of these patients. The prognostic value of kidney
      function in patients with STEMI and NSTEMI treated predominantly with
      percutaneous coronary intervention (PCI) and aggressive medical treatment is less
      known. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2 academic
      centers in Germany; 4,701 consecutive patients with acute myocardial infarction
      (AMI) from 1998 to 2006. PREDICTOR: Estimated creatinine clearance (eCCr) at
      admission. OUTCOMES & MEASUREMENTS: The primary end point was all-cause mortality
      during the first year after PCI for AMI (STEMI and NSTEMI) with a prespecified
      landmark at 30 days (landmark analysis). Secondary end points were nonfatal
      myocardial infarction, stroke, and major bleeding. RESULTS: Patients were divided
      into quartiles according to eCCr less than 56, 56 to 76, 77 to 100, and greater
      than 100 mL/min. Patients had an increased risk of death with decreased eCCr both
      within 30 days (7.7%, 3.1%, 1.4%, and 0.7% for the 4 quartiles; P < 0.001) and
      after 30 days (12.1%, 4.8%, 1.9%, and 1.2%; P < 0.001). The association of eCCr
      with mortality was similar in patients younger and older than 70 years. Major
      bleeding within 30 days and incidence of stroke also were more frequent with
      reduced eCCr. However, recurrent myocardial infarction was not associated with
      eCCr. After adjustment for additional baseline characteristics, kidney function
      based on eCCr at admission remained a strong independent predictor of mortality
      at 1 year after AMI (hazard ratio, 1.21 per 10-mL/min decrease; 95% confidence
      interval, 1.13 to 1.30). LIMITATIONS: Single assessment of eCCr. CONCLUSIONS: In
      patients with AMI treated with primary PCI for STEMI and early PCI for NSTEMI,
      eCCr at admission remains a powerful independent predictor of short- and long
      term mortality.

PMID- 19592143
TI  - Epidemiology, diagnosis, and management of depression in patients with CKD.

PMID- 19592146
TI  - Acute kidney injury in a patient with unilateral ureteral obstruction.

PMID- 19592148
TI  - Demographic data in asthma clinical trials: a systematic review with implications
      for generalizing trial findings and tackling health disparities.
AB  - The prevalence of asthma, and the morbidity, adverse events, mortality and
      healthcare utilisation of asthmatic patients vary widely among racial/ethnic and
      other socio-demographic groups. Debates over the meanings of race and ethnicity
      and the strategic need to resolve health inequalities have prompted extensive
      recommendations for reporting and analyzing racial/ethnic and demographic
      information in clinical trials. We conducted a systematic review to determine the
      extent to which race/ethnicity, socio-economic status and other demographic
      variables are analyzed and reported in publications from randomized controlled
      trials of asthma interventions. Randomized controlled trials of inhaled
      corticosteroids and long-acting beta-agonists in asthmatic patients were
      identified by systematically searching 12 electronic bibliographic databases. We
      identified peer-reviewed papers reporting 87 relevant trials published during
      1985-2006, from which we extracted data on patients' race/ethnicity, ancestry,
      gender, socio-economic variables and geographical attributes. The proportion of
      the papers reporting the race/ethnicity of their participants was lower than
      would be expected by chance and has recently declined. None of the papers
      included race/ethnicity or gender in statistical analyses or reported socio
      economic variables, ancestry, or genetic data for their participants, and few
      discussed the generalizability of their findings. The frequency of reporting
      race/ethnicity was statistically significantly lower in trials conducted in the
      UK than in the US, but 23 of the 87 papers did not identify countries. Despite
      extensive recommendations in the literature, guidance from health agencies on
      analyzing and reporting demographic data in clinical trials still appears
      inconsistent and vague. There remains a need to improve guidance on the
      representation and analysis of minority populations in asthma clinical trials, in
      order to encourage transparent reporting of population selection, analysis
      approaches, and trial generalizability. To assist this process, asthma clinical
      trials should be based on clear hypotheses that link both to existing demographic
      evidence and to demographic healthcare goals.

PMID- 19592149
TI  - [Neoplasia in lung transplants].

PMID- 19592152
TI  - Genetic polymorphisms in DNA repair gene APE1, XRCC1 and XPD and the risk of pre
      eclampsia.
AB  - OBJECTIVE: Oxidative stress has been postulated as a major contributor to
      placental hypoperfusion and ischemia in pre-eclampsia (PE). Reactive oxygen
      species (ROS) generated during placental ischemia can cause oxidative damage to
      nucleic acids. Base excision repair (BER) and nucleotide excision repair (NER)
      are major pathways responsible for removing the oxidative DNA damage.
      Polymorphisms in DNA repair genes may be associated with differences in the
      repair efficiency of DNA damage. STUDY DESIGN: In order to investigate the
      possible association between DNA repair genes and PE susceptibility, we analyzed
      genotype and allele distributions of APE1-148, XRCC1-194, XRCC1-399 and XPD-751
      genes in 101 patients with PE and 107 healthy women. Differences in genotype
      distributions and allele frequencies in the cases and the controls were compared
      for statistical significance using the chi(2)-test. Haplotype frequencies were
      estimated using a contingency chi(2)-test. One-way ANOVA and Mann-Whitney U-test
      were used for the statistics of the clinical and biochemical parameters. RESULTS:
      No significant association between PE and the variant alleles of APE1 codon 148
      (OR: 0.77, 95% CI=0.51-1.15), XRCC1 codon 194 (OR: 0.64, 95% CI=0.30-1.37), XRCC1
      codon 399 (OR: 1.16, 95% CI=0.78-1.74) and XPD codon 751 (OR: 1.21, 95% CI=0.81
      1.80) was observed. Results of our haplotype analysis demonstrated that there is
      a high linkage disequilibrium (D': 1.0, r(2)=0.042) between the haplotypes of
      XRCC1 codon 194 and codon 399 markers. CONCLUSIONS: These preliminary results
      suggest that the polymorphic variants of APE1-148, XRCC1-194, XRCC1-399, and XPD
      751 genes are not significant risk factors for PE development.

PMID- 19592147
TI  - Gender differences in factors influencing alcohol use and drinking progression
      among adolescents.
AB  - While prevalence rates for alcohol use and related disorders differ widely
      between adult men and women, male and female adolescents do not exhibit the same
      disparity in alcohol consumption. Previous research and reviews do not address
      the emergence of differences in drinking patterns that occur during late
      adolescence. Therefore, a developmental perspective is presented for
      understanding how various risk and protective factors associated with problematic
      drinking affect diverging alcohol trajectories as youth move into young
      adulthood. This review examines factors associated with risk for developing an
      alcohol use disorder in adolescent girls and boys separately. Findings indicate
      that certain biological (i.e., genetic risk, neurological abnormalities
      associated with P300 amplitudes) and psychosocial (i.e., impact of positive
      drinking expectancies, personality characteristics, and deviance proneness)
      factors appear to impact boys and girls similarly. In contrast, physiological and
      social changes particular to adolescence appear to differentially affect boys and
      girls as they transition into adulthood. Specifically, boys begin to manifest a
      constellation of factors that place them at greater risk for disruptive drinking:
      low response to alcohol, later maturation in brain structures and executive
      function, greater estimates of perceived peer alcohol use, and socialization into
      traditional gender roles. On an individual level, interventions which challenge
      media-driven stereotypes of gender roles while simultaneously reinforcing
      personal values are suggested as a way to strengthen adolescent autonomy in terms
      of healthy drinking decisions. Moreover, parents and schools must improve
      consistency in rules and consequences regarding teen drinking across gender to
      avoid mixed messages about acceptable alcohol use for boys and girls.

PMID- 19592150
TI  - Family witnessed resuscitation: the views and preferences of recently
      resuscitated hospital inpatients, compared to matched controls without the
      experience of resuscitation survival.
AB  - AIM OF THE STUDY: To compare the preferences of patients who survived
      resuscitation with those admitted as emergency cases about whether family members
      should be present during resuscitation. METHODS: We used a case control design
      and recruited, from four large hospitals, 21 survivors of resuscitation and 40
      patients admitted as emergency cases without the experience of resuscitation
      (control group) who were matched by age and gender at a ratio of 1:2. Data
      collection involved face-to-face interviews using a standardised 22 item
      questionnaire. Data analysis sought to identify differences between the two
      groups. RESULTS: Both groups were broadly supportive of the practice, however
      resuscitated patients were more likely to favour witnessing the resuscitation of
      a family member (72% versus 58%), preferred to have a relative present in the
      event they required resuscitation (67% versus 50%) and believed that relatives
      benefited from such an experience (67% versus 48%). Additionally, both groups
      indicated that staff should seek patient preferences about family witnessed
      resuscitation following hospital admission, and stated that they were unconcerned
      about confidential matters being discussed with family members present during
      resuscitation (91% and 75%, respectively). However none of these differences
      between the two groups achieved statistical significance. CONCLUSION:
      Hospitalised patients report a favourable disposition towards family witnessed
      resuscitation, and this view appears to be strengthened by successfully surviving
      a resuscitation episode. Practitioners should strive to facilitate family
      witnessed resuscitation by establishing, documenting and enacting patient
      preferences. Research exploring the perceptions of the wider public would help
      further inform this debate.

PMID- 19592153
TI  - Risk of water contamination by nitrogen in Canada as estimated by the IROWC-N
      model.
AB  - With increasing amounts of nitrogen (N) being added to farmland in the form of
      fertilizer and manure to optimize crop yields, and more broadly, to meet the
      growing demands for food, feed and energy, there are public concerns regarding
      its possible negative impact on the environment. An optimal balance between N
      requirements for production versus efficient N use is required, so as to minimize
      N losses from the agricultural system. An agri-environmental indicator i.e., the
      Indicator of the Risk of Water Contamination by Nitrogen (IROWC-N) was developed
      to assess the risk of N moving from agricultural areas into groundwater and/or
      nearby surface water bodies. The indicator linked the quantity of mineral
      nitrogen remaining in the soil at harvest, i.e., the Residual Soil Nitrogen (RSN)
      indicator, and the subsequent climatic conditions during the winter period. The
      results were assessed in terms of nitrate lost through leaching and nitrate
      concentration in the drainage water, expressed in five IROWC-N risk classes.
      Unlike previous versions of the indicator, the current model provided a more
      complete description of the soil-water balance, including the calculation of
      rainfall interception by crops, surface runoff, actual evapotranspiration and
      soil-water contents. Consequently, the current IROWC-N estimates differed
      markedly from those obtained previously. Between 1981 and 2006, the risk of water
      contamination by N in Canada was small, and reflected what was happening in the
      three Prairie provinces where 85% of Canada's farmland is located. However, the
      aggregated IROWC-N index, which is a combination of all five risk classes,
      increased steadily by 2.3% per year, from 6.7 in 1981 to 10.6 in 2006. The
      proportion of farmland in the very low IROWC-N risk class decreased from 88 to
      78%; correspondingly, the proportion in the low risk class increased from 2 to
      12%. The proportion of farmland in the moderate-, high- and very high-risk
      classes changed by less than 3% over time. The trends in IROWC-N in the Atlantic
      provinces were significantly worse than the national trend; for example, in
      Atlantic Canada, the aggregated IROWC-N index tripled from 27.8 in 1981 to 87.5
      in 2006. Increases in fertilizer use (except in British Columbia), increases in
      livestock numbers in Manitoba and the Atlantic provinces, and an increase in
      legume crop acreage were the main factors that contributed to the increase in
      IROWC-N estimates. Climatic factors were also involved, as droughts reduced
      yields, N uptake and N leaching in many regions of Canada in 2001.

PMID- 19592157
TI  - Biomineralization of N,N-dimethylformamide by Paracoccus sp. strain DMF.
AB  - N,N-dimethylformamide (DMF) is a man-made compound that is widely used as a
      solvent for the synthesis of various organic compounds. In this study, a
      bacterial strain Paracoccus sp. DMF capable of using DMF as the sole carbon,
      nitrogen and energy source, was isolated from an enrichment culture developed
      using activated sludge from domestic waste water treatment unit as the source
      inoculum. The strain DMF was characterized by biochemical tests and 16S rDNA
      sequence analysis, to be belonging to the genus Paracoccus. Growth on DMF was
      accompanied with ammonia release and the total organic carbon (TOC) analysis
      indicated its extensive mineralization. Batch culture studies were conducted in
      the substrate range of 100-5000 mg L(-1) to determine the biokinetic constants.
      Strain Paracoccus sp. DMF could tolerate very high concentrations of DMF as the
      growth was observed even at 15000 mg L(-1). High (micro(max)) and (K(i)) showed
      the suitability of the strain for the treatment of DMF containing waste water.
      Transient accumulation of dimethylamine (DMA) in the medium during the growth on
      DMF and utilization of DMA and monomethylamine (MMA) as growth substrates by
      Paracoccus sp. strain DMF showed that the pathway of DMF degradation involves DMA
      and MMA as intermediates, ultimately leading to the formation of carbon dioxide
      (CO(2)) and ammonia (NH(3)).

PMID- 19592155
TI  - Laparoscopic kidney transplantation.
AB  - We present the details of the first laparoscopic transplantation of a kidney from
      a living, related donor, performed April 16, 2009. Surgical and functional
      results were acceptable. Surgical time was 240 min (53 min for vascular suture),
      with blood loss of 300 cm(3) and a hospital stay of 14 d. Serum creatinine at
      discharge was 73 mmol/l. Laparoscopic kidney transplantation is a complex
      technique that requires previous experience in vascular and laparoscopic surgery.
      As with all novel procedures, technical modifications will be required to
      formalize its use and detailed comparisons will need to be made with standard
      procedures.

PMID- 19592159
TI  - Evaluation of electrochemical oxidation techniques for degradation of dye
      effluents--a comparative approach.
AB  - The high energy cost of an electrochemical method is the fatal drawback that
      hinders its large scale application in wastewater treatment. The traditional
      single-chamber electrochemical method used in the waste water treatment mainly
      focused on anodic oxidation, but hydrogen produced on the cathode and indirect
      electrochemical treatment involves application of an electrical current to the
      wastewater containing chloride to convert into chlorine/hypochlorite. The two
      compartment electrolytic cell, separated by an anion exchange membrane, has been
      developed in this work. In the new reactor, indirect oxidation at anode, indirect
      oxidation by hydrogen peroxide and ultraviolet/hydrogen peroxide (UV/H(2)O(2)) at
      cathode can occur simultaneously. The electrochemically produced hydrogen
      peroxide at the cathode by reduction of oxygen is affected by passing atmospheric
      air. Therefore "dual electrochemical oxidation" in one electrochemical reactor
      was achieved successfully. Compared to a traditional one-cell reactor, this
      reactor reduces the energy cost approximately by 25-40%, and thus the present
      work becomes significant in wastewater treatment. Experiments were carried out at
      different current densities using Ti/RuO(2)/IrO(2) as anode and carbon felt gas
      diffusion electrode used as a cathode fed with oxygen containing gases to produce
      hydrogen peroxide. During the various stages of electrolysis, the parameters such
      as, effect of pH, chemical oxygen demand (COD), colour, energy consumption were
      monitored. UV-vis spectrometry, Fourier transform infrared spectroscopy (FTIR),
      high-performance liquid chromatography (HPLC) studies were carried out to assess
      efficiencies of dye degradation.

PMID- 19592160
TI  - An evaluation of suspicious powder screening tools for first responders.
AB  - Field screening tools are required which would allow first responders to quickly
      ascertain if a suspicious powder poses a potential threat necessitating
      additional testing for biological pathogens such as Bacillus anthracis. In this
      study, three commercially available generic screening technologies were evaluated
      for the effectiveness to accurately differentiate between a hoax powder and a
      true biological threat. The BioCheck Kit was able to detect the following
      biological agents 1 x 10(8)CFU of B. anthracis Sterne (washed 4 times),
      1x10(7)CFU of B. anthracis DeltaSterne (washed 2 times), 1 x 10(7)CFU of Yersinia
      pestis A1122, and 100 microg of ricin. The Prime Alert kit was able to detect 2 x
      10(10)CFU of B. anthracis DeltaSterne 4x, 1 x 10(9)CFU of B. anthracis
      DeltaSterne 2x, and 1 x 10(8)CFU of Y. pestis A1122. The Prime Alert kit was not
      able to detect ricin. The Profile-1 kit was able to detect 1 x 10(4)CFU of B.
      anthracis DeltaSterne 4x and B. anthracis DeltaSterne 2x, and 1 x 10(6)CFU of Y.
      pestis A1122. The Profile-1 kit was not able to detect ricin. All of the kits
      showed positive results for powders containing components specifically targeted
      by the particular technology being used. Each technology assessed in this
      evaluation employs a different mechanism for the detection of biological
      materials and it is important that first responders are aware of the strengths
      and the limitations of each system so that they can effectively employ the
      technology to protect the homeland.

PMID- 19592158
TI  - Combined effects of Cu, Cd, Pb, and Zn on the growth and uptake of consortium of
      Cu-resistant Penicillium sp. A1 and Cd-resistant Fusarium sp. A19.
AB  - Microorganisms can be important biosorbents for heavy metal remediation of
      contaminated soils and wastewaters. With different types and concentrations of
      heavy metals, strains display different resistance and removal abilities to the
      heavy metals. The objective of this study was to investigate the effects of
      single and multiple heavy metals on the growth and uptake of consortium of two
      types of fungal strains, Penicillium sp. A1 and Fusarium sp. A19. These fungal
      strains were tested to be tolerant to several heavy metals. A1, A19, and their
      combination (A1+A19) were inoculated on potato dextrose agar (PDA), Czapek Dox
      agar (CDA), and potato dextrose broth (PDB) containing Cu(2+), Cd(2+), Pb(2+),
      and Zn(2+). Experimental results showed that the combined inoculation of A1 and
      A19 had profound effects on the growth of the two fungi in PDA and CDA under the
      treatments with Cu(2+) and mixed Cd(2+)+Zn(2+). The amount of metals through
      bioaccumulation by A1, A19, and A1+A19 was significantly higher than that through
      biosorption by these fungi. The highest amount of Cd, Cu, and Zn accumulated by
      fungal biomass was obtained in the presence of Cd(2+)+Cu(2+)+Zn(2+) in PDB.
      Compared with the individual A1 or A19 used in PDB, A1+A19 accumulated higher
      amount of Cu and Pb in the presence of Cd(2+)+Cu(2+)+Pb(2+) and higher amount of
      Pb in the presence of Cd(2+)+Cu(2+)+Zn(2+)+Pb(2+). Our results indicated that
      there was no simple relationship between the metal biosorption by fungal biomass
      and the fungal metal tolerance. The biomass of A1+A19 cultivated in PDB absorbed
      higher amount of metals than A1 or A19 in the presence of single metals and their
      combinations. The results suggested that the applicability of growing fungi
      tolerant to heavy metals provided a potential biotechnology for treatment of
      wastewaters with heavy metal pollutions.

PMID- 19592161
TI  - Removal of chromium (III) by using coal as adsorbent.
AB  - The adsorption of Cr(III) by two different coal varieties from Lakhra and Thar
      coalfields (Pakistan) have been studied in batch mode. The effect of adsorbent
      dose, pH, contact time and agitation speed on the adsorption of Cr(III) by both
      the coals were investigated. Adsorption equilibrium was achieved in 40-50 min.
      The Langmuir, Freundlich and Temkin adsorption isotherms were used to elucidate
      the observed sorption phenomena. The maximum Cr(III) removal was 2.61 mg of
      Cr(III) per gram of LC (Lakhra coal) and 2.55 mg of Cr(III) per gram of TC (Thar
      coal) as evaluated from Langmuir isotherm. The heat of sorption was in the range
      3.75-3.87 kJ/mol as evaluated from Temkin isotherm. Best results were obtained at
      pH>5. It is proposed that low rank coals of Pakistan can be used for removal of
      toxic metals like Cr(III) from industrial effluents/waste waters.

PMID- 19592162
TI  - Effects of crystalline structures and surface functional groups on the adsorption
      of haloacetic acids by inorganic materials.
AB  - The effects of the crystalline structure and surface functional groups of porous
      inorganic materials on the adsorption of dichloroacetic acid (DCAA) were
      evaluated by using hexagonal mesoporous silicates (HMS), two surface functional
      group (3-aminopropyltriethoxy- and 3-mercaptopropyl-) modified HMSs, faujasite Y
      zeolite and activated alumina as adsorbents, and compared with powdered activated
      carbon (PAC). Selective adsorption of HAA(5) group was studied by comparing
      single and multiple-solute solution, including effect of common electrolytes in
      tap water. Adsorption capacities were significantly affected by the crystalline
      structure. Hydrogen bonding is suggested to be the most important attractive
      force. Decreasing the pH lower than the pH(zpc) increased the DCAA adsorption
      capacities of these adsorbents due to electrostatic interaction and hydrogen
      bonding caused by protonation of the hydronium ion. Adsorption capacities of
      HAA(5) on HMS did not relate to molecular structure of HAA(5). Common
      electrolytes did not affect the adsorption capacities and selectivity of HMS for
      HAA5, while they affected those of PAC.

PMID- 19592163
TI  - Isolation of Streptomyces sp. strain capable of butyltin compounds degradation
      with high efficiency.
AB  - Dibutyltin (DBT), a widely used plastic stabilizer, has been detected in the
      environment as well as in human tissues. DBT is considered to be highly
      neurotoxic and immunotoxic. Hence, DBT needs to be considered as a potential
      toxic chemical. Degradation of butyltin compounds by Streptomyces sp. isolated
      from plant waste composting heaps was studied. Glucose grown cells degraded
      organotin from 10 to 40 mg l(-1). After 1 day of incubation 90% of DBT (added at
      20 mg l(-1)) was converted to less toxic derivative--monobutyltin (MBT). DBT
      metabolism was inhibited by metyrapone addition, a known cytochrome P-450
      inhibitor. It could provide evidence that cytochrome P-450 system is involved in
      DBT metabolism in Streptomyces sp. IM P102. Moreover, according to our knowledge,
      the degradation of DBT by actinobacterium has not been previously described.

PMID- 19592164
TI  - A preliminary study on the adsorptive removal of Cr(VI) using seaweed, Hydrilla
      verticillata.
AB  - The Cr(VI) adsorption efficiency of the seaweed, Hydrilla verticillata, was
      studied in batches. The adsorbent was characterized using SEM, BET surface area
      analyzer, Malvern particle size analyzer, EDAX and FT-IR. Cr(VI) removal
      efficiency of the adsorbent was studied as a function of different adsorption
      parameters such as contact time, stirring speed, pH, adsorbent dose, particle
      size, adsorbate concentration, and temperature. Langmuir, Freundlich, and Temkin
      adsorption isotherm equations were used in the equilibrium modeling. The
      adsorption process followed pseudo second-order kinetics and intra-particle
      diffusion was found to be the rate-controlling step. Experimental data follow
      Langmuir adsorption isotherm. Thermodynamic parameters such as Gibbs free energy
      and enthalpy of the adsorption process were evaluated to find out the feasibility
      of the adsorption process. The negative values of Gibb's free energy and positive
      enthalpy values show the feasibility and endothermic nature of the process. The
      significance of different adsorption parameters along with their combined effect
      on the adsorption process has been established through a full 2(4) factorial
      design. Among the different adsorption parameters, pH has the most influential
      effect on the adsorption process followed by adsorbate concentration and combined
      effects of all the four parameters were tested. The correlation among different
      adsorption parameters were studied using multi-variate analysis.

PMID- 19592165
TI  - Flammability limits of olefinic and saturated fluoro-compounds.
AB  - Flammability limits were measured for a number of olefinic and saturated fluoro
      compounds in a 12l spherical glass vessel. The obtained data together with the
      ones of previous studies have been analyzed based on the F-number scheme of
      flammability limits. The flammability limits of these compounds have been found
      to be explained very well by the present scheme of interpretation. The
      flammability limits are dependent upon distribution of F atoms in a molecule as
      well as upon F-substitution rate itself. It has been found that -O-CF(3) group in
      a molecule conspicuously decreases the flammability of the compound, while -C
      CF(3) group does not much. For olefinic compounds, distribution of F atoms around
      double bonds markedly diminishes the flammability of the molecule.

PMID- 19592166
TI  - A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy
      and postherpetic neuralgia: Differences in demographic data and sensory symptoms.
AB  - Patients with neuropathic pain syndromes are heterogeneous. They present with a
      variety of sensory symptoms and pain qualities. The knowledge of these data and
      etiology-specific differences is important to optimize clinical trial design and
      to develop more effective drugs. This investigation uses epidemiological and
      clinical data on the symptomatology of 2100 patients with painful diabetic
      neuropathy (DPN) and postherpetic neuralgia (PHN) from a cross-sectional survey
      (painDETECT) to (1) describe characteristic epidemiological differences, (2)
      analyse typical patterns of sensory symptoms in both cohorts and (3) determine
      whether questionnaires can capture these characteristics. PHN patients suffer
      more often from clinically relevant sensory disturbances although the average
      pain intensity is only marginally higher. This difference is particularly obvious
      with dynamic mechanical allodynia which is present in half of the PHN patients
      and in 18% of the DPN patients. Thermal hyperalgesia occurs twice as often in
      PHN. Numbness is described more often in DPN. Age has no influence on sensory
      symptoms in both entities. A hierarchical cluster analysis revealed five distinct
      subgroups of patients showing a characteristic sensory profile, a typical
      constellation and combination of neuropathic symptoms. All subgroups occur in
      relevant numbers in both entities but the frequencies differ between PHN and DPN.
      Since sensory symptoms likely translate into pain-generating mechanisms
      enrichment for potential treatment responders might be possible in clinical
      trials by assessing the sensory profiles. Patient-Reported Outcomes can be used
      to obtain a precise sensory characterization of each patient.

PMID- 19592167
TI  - Excitatory and inhibitory pain mechanisms during the menstrual cycle in healthy
      women.
AB  - Sex differences in pain perception have been clearly documented in the literature
      during the last decades and it has been shown that women perceived more pain than
      men. Sex hormones (SHs) are thought to be one of the main mechanisms which
      explain sex differences in pain. Pain is a dynamic phenomenon involving both
      excitatory and inhibitory mechanisms. Previous studies have verified the effect
      of SH on excitatory mechanisms but not on endogenous pain inhibitory mechanisms.
      The main objective of this study was to establish if pain perception and diffuse
      noxious inhibitory control (DNIC) vary across the menstrual cycle (MC). Thirty
      two healthy women with a regular MC were tested three times across their MC (days
      1-3, days 12-14 and days 19-23). Experimental pain consisted of two tonic heat
      pain stimulations (thermode) separated by a 2-min cold pressor test (CPT)
      (conditioning stimulus activating DNIC). Pain ratings were measured with a visual
      analogue scale. Heat pain threshold, pain tolerance and mean pain intensity
      during both the 2-min thermode test and CPT did not vary throughout the MC.
      However, we found significantly more pain inhibition (DNIC effectiveness) during
      the ovulatory phase compared to the menstrual and luteal phases (p=0.05). The
      main finding of this study is the observation that only inhibitory mechanisms
      (DNIC analgesia) and not excitatory pain mechanisms vary throughout the MC, where
      women have greater DNIC in the ovulatory phase. The higher occurrence of pain and
      lower pain threshold previously reported during the MC could be related to a
      reduction in endogenous pain control mechanisms.

PMID- 19592168
TI  - Clustering and nearest neighbour distances in atom-probe tomography.
AB  - The measurement of chemical composition of tiny clusters is a tricky problem in
      both atom-probe tomography experiments and atomic simulations. A new approach
      relying on the distribution of the first nearest neighbour (1NN) distances
      between solute atoms in the 3D space composed of A and B atoms was developed.
      This new approach, the 1NN method, is shown to be an elegant way to get the
      composition of tiny B-enriched clusters embedded in a random AB solid solution.
      The theoretical statistical distributions of first neighbour distances P(r) for
      both random solid solution and solute-enriched clusters finely dispersed in a
      depleted matrix are established. It is shown that the most probable distance of
      P(r) gives directly the phase composition. Applications of this model to both one
      phase SiGe alloy and boron-doped silicon containing small clusters indicate that
      this new approach is quite reliable.

PMID- 19592170
TI  - Genetic characterization of Toxoplasma gondii from wild boar (Sus scrofa) in
      France.
AB  - Toxoplasma gondii strains isolated from domestic animals and humans have been
      classified into three clonal lineages types I-III, with differences in terms of
      pathogenicity to mice. Much less is known on T. gondii genotypes in wild animals.
      In this report, genotypes of T. gondii isolated from wild boar (Sus scrofa) in
      France are described. During the hunting seasons 2002-2008, sera and tissues of
      individuals from two French regions, one continental and one insular, were tested
      for Toxoplasma infection. Antibodies to T. gondii were found in 26 (17.6%) of 148
      wild boars using the modified agglutination test (MAT, positivity threshold:
      1:24). Seroprevalence was 45.9% when considering a threshold of 1:6. Hearts of
      individuals with a positive agglutination (starting dilution 1:6) (n=60) were
      bioassayed in mice for isolation of viable T. gondii. In total, 21 isolates of T.
      gondii were obtained. Genotyping of the isolates using 3 PCR-restriction fragment
      length polymorphism markers (SAG1, SAG2 and GRA7) and 6 microsatellite loci
      analysis (TUB2, TgM-A, W35, B17, B18 and M33) revealed that all belonged to type
      II lineage. These results underline that wild boar may serve as an important
      reservoir for transmission of T. gondii, and that strains present in wildlife may
      not be different from strains from the domestic environment.

PMID- 19592172
TI  - Protective immune response in BALB/c mice induced by a suicidal DNA vaccine of
      the MIC3 gene of Toxoplasma gondii.
AB  - To evaluate the protective efficiency of a suicidal DNA vaccine against protozoal
      parasite Toxoplasma gondii, the microneme protein 3 (MIC3) gene was cloned into
      suicidal vector pSCA1 and conventional DNA vaccine vector pcDNA3.1+ respectively,
      their protection against T. gondii challenge were assessed in this study. The
      recombinant plasmids named pSCA/MIC3 and pcDNA/MIC3 were transfected into BHK-21
      cells. The expression of MIC3 in BHK-21 cells was confirmed by RT-PCR and
      indirect immunofluorescence test. Then BALB/c mice were immunized with pSCA/MIC3
      or pcDNA/MIC3. Anti-Tg-MIC3 antibodies were detected by indirect ELISA and the
      cell immune response were examined by lymphocyte proliferation assay and real
      time RT-PCR. The results showed that the titre of anti-Tg-MIC3 antibodies,
      stimulation index (SI) of lymphocyte proliferation response and IFN-gamma
      expression level induced by pSCA/MIC3 and pcDNA/MIC3 were significantly higher
      than controls (P<0.05), whereas IL-4 expression level in BALB/c mice immunized
      with either pSCA/MIC3 or pcDNA/MIC3 was lower than that in control group. After a
      lethal challenge against T. gondii, survival time of the mice immunized with this
      suicidal DNA vaccine pSCA/MIC3 and conventional DNA vaccine pcDNA/MIC3 were
      significantly prolonged in comparison with the control groups (P<0.05), but the
      difference of protective immune response in BALB/c mice between pSCA/MIC3 and
      pcDNA/MIC3 was not statistically significant (P>0.05). The findings demonstrated
      that like conventional DNA vaccine pcDNA/MIC3, suicidal DNA vaccine pSCA/MIC3
      also provided favourable efficacy, but it could improve the biosafety of
      conventional vaccines. This result suggested that suicidal DNA vaccine pSCA/MIC3
      is a potential candidate vaccine against toxoplasmosis.

PMID- 19592171
TI  - Seroprevalence of Neospora caninum in dairy cattle ranches with high abortion
      rate: special emphasis to serologic co-existence with Toxoplasma gondii, Brucella
      abortus and Listeria monocytogenes.
AB  - The aim of this study was to determine seroprevalence of Neospora caninum in
      dairy cattle ranches with higher abortion rates and co-existence of Neospora
      caninum, Toxoplasma gondii, Brucella abortus, and Listeria monocytogenes
      antibodies. The blood samples were collected from dairy cows with history of
      abortion (n=234) as well as from pregnant cows that were (n=323) kept in the same
      ranches. N. caninum seroprevalence was 10.77% (60/557). The co-existence rate of
      N. caninum seropositivity with T. gondii, B. abortus and L. monocytogenes was
      24.77% (138/557), 13.82% (77/557) and 42.85% (162/378), respectively. Only one
      animal had significant antibody titers for all analyzed infectious agents. The
      seroprevalence of N. caninum and T. gondii were significantly higher in pregnant
      cows than aborted cows (p<0.05 and p<0.001, respectively). As a result, the
      comprehensive data generated through this study can significantly contribute to
      understanding of serologic association of N. caninum with T. gondii, B. abortus
      and L. monocytogenes in pregnant and aborted dairy cows.

PMID- 19592173
TI  - Comparative evaluation and economic assessment of coprological diagnostic methods
      and PCR for detection of Cryptosporidium spp. in bovines.
AB  - The role of Cryptosporidium spp. as a major cause of diarrhoea and
      gastrointestinal illness of protozoan origin in neonatal calves has been
      established. Many coprological and serological techniques have been described for
      detection of the parasites with the limitations of sensitivity and specificity.
      Polymerase chain reaction (PCR) technique offers a useful alternative to
      conventional diagnosis of Cryptosporidium spp. in bovines from both clinical and
      environmental samples. We compared four conventional coprological techniques,
      viz., direct faecal smear staining (DFSS), normal saline sedimentation staining
      (NSSS), Sheather's flotation (SF) and Sheather's flotation sedimentation staining
      (SFSS) with PCR directed against the 18S SSU rRNA gene as standard reference test
      for the diagnosis of cryptosporidiosis in bovines. Out of 457 faecal samples
      collected from neonatal bovine calves, specific PCR amplification was achieved in
      138 samples, whereas, 65 samples turned positive by DFSS. Normal saline
      sedimentation staining, SF and SFSS could detect 92, 82 and 109 samples as
      positive, respectively. Sheather's flotation sedimentation staining was found to
      be the most sensitive (82.6%) and specific (98.76%) among the coprological
      techniques. On per sample processing based cost analysis, DFSS was found to be
      the most economical method (15 cents) followed by NSSS (19.6 cents), SF (23.6
      cents) and SFSS (33.9 cents). The time taken for complete processing and
      diagnosis varied between 70 and 100 min. PCR based diagnosis of a sample took
      about 7.5-8h for completion and cost of diagnosis was estimated as approximately
      7.604 US$ per sample. Among the conventional coprological methods, SFSS provided
      the required sensitivity and specificity along with nominal cost for diagnosis on
      per sample basis, and may be considered as a viable diagnostic alternative when
      PCR is not an option for a particular laboratory setting, especially in
      developing countries. This is the first comparative study describing the
      sensitivity and specificities of four conventional coprological techniques
      altogether with respect to PCR along with the economic assessment and per sample
      diagnosis time of all the techniques for the diagnosis of cryptosporidiosis in
      bovines.

PMID- 19592174
TI  - Serum chemokine levels in major depressive disorder.
AB  - OBJECTIVE: To examine the role of chemokines of two major chemokine families, CC
      and CXC, in major depressive disorder (MDD) in a population-based sample. METHOD:
      The serum levels of CC chemokines MCP-1 and MIP-1beta, and CXC chemokine IL-8
      were measured from 122 participants (MDD group, n=61; controls, n=61). Depression
      severity was assessed with the 29-item Hamilton Depression Rating Scale. RESULTS:
      The MDD group had lower levels of MCP-1, MIP-1beta and IL-8 than the healthy
      controls. The likelihood of major depressive disorder for participants with
      chemokine levels below the median (MCP-1: < 26.26 pg/mL; MIP-1beta: < 42.57
      pg/mL; IL-8: < 2.86 pg/mL) was 3.6 (p=0.002) for MIP-1beta and 2.4 (p=0.037) for
      IL-8 in regression models adjusted for age, gender, body mass index, smoking, and
      alcohol consumption. MCP-1 did not associate with the presence of MDD after
      adjustments for potential confounders. Further adjustments for somatic illnesses
      or medications did not affect these findings. CONCLUSION: Our findings suggest
      that depression-related alterations of inflammatory markers may be more complex
      than previously assumed, and that at least some of the chemokines may be down
      regulated.

PMID- 19592175
TI  - Angiogenesis in chronic hepatitis C is associated with inflammatory activity
      grade and fibrosis stage.
AB  - Data regarding the assessment of angiogenesis in liver tissue in chronic
      hepatitis C (CHC) are rare. The study was performed to explain the association
      between the histopathological features and the number of new blood vessels in
      lobules and portal tracts in CHC. The second aim of the study was to define the
      localization of sprouting and pattern of formation of new vessels by estimating
      CD 34 antigen expression in the liver. The study involved 74 patients with CHC,
      infected with viral genotype 1b before antiviral therapy. The number of new
      formatted blood vessels was positively associated with fibrosis stage and
      inflammatory activity grade in the liver biopsy from CHC patients. The
      relationship was evident in the portal tract, fibrous septa and periportal zones
      of lobules. The results suggest that inflammatory hepatocyte injury may promote
      neo-angiogenesis.

PMID- 19592178
TI  - Inducible clindamycin-resistance in methicillin-resistant Staphylococcus aureus
      and methicillin-resistant Staphylococcus pseudintermedius isolates from dogs and
      cats.

PMID- 19592176
TI  - D-Cycloserine attenuates reactivity to smoking cues in nicotine dependent
      smokers: a pilot investigation.
AB  - Increasing evidence indicates that smoking cues contribute to nicotine self
      administration and attenuating conditioned reactivity to smoking cues may aid
      abstinence of smoking and prevention of smoking relapse in individuals with
      nicotine dependence. Based on prior studies showing that the partial N-methyl-D
      aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of learned
      fear during behavioral exposure therapy in humans and facilitates extinction of
      cocaine-induced conditioned place preference in animals, we evaluated whether DCS
      would have potential for reducing reactivity to smoking cues when combined with
      cue exposure treatment in humans with nicotine dependence. In this double-blind
      placebo-controlled pilot laboratory study, 25 smokers were recruited from the
      general community and randomized to DCS or placebo, plus cue exposure therapy.
      DCS significantly attenuated smoking cue reactivity in response to in-vivo
      smoking cues based on physiological reactivity and subjective urge-to-smoke
      ratings and led to a significantly smaller expired carbon monoxide (CO) level at
      the one-week follow-up compared to placebo, although exploratory analyses
      indicated no effect on smoking behavior overall. These findings provide promising
      support for DCS combined with cue exposure therapy in attenuating conditioned
      reactivity to smoking cues.

PMID- 19592177
TI  - In contrast to human isolates animal isolates of S. saprophyticus subsp.
      saprophyticus are not internalized into human urinary bladder carcinoma cell line
      5637.

PMID- 19592179
TI  - The reduction of CSFV transmission to untreated pigs by the pestivirus inhibitor
      BPIP: a proof of concept.
AB  - 5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a
      representative molecule of a novel class of highly active in vitro inhibitors of
      the replication of Classical swine fever virus (CSFV). We recently demonstrated
      in a proof of concept study that the molecule has a marked effect on viral
      replication in CSFV-infected pigs. Here, the effect of antiviral treatment on
      virus transmission to untreated sentinel pigs was studied. Therefore, BPIP
      treated pigs (n=4), intra-muscularly infected with CSFV, were placed into contact
      with untreated sentinel pigs (n=4). Efficient transmission of CSFV from four
      untreated seeder pigs to four untreated sentinels was observed. In contrast, only
      two out of four sentinel animals in contact with BPIP-treated seeder animals
      developed a short transient infection, of which one was likely the result of
      sentinel to sentinel transmission. A significant lower viral genome load was
      measured in tonsils of sentinels in contact with BPIP-treated seeder animals
      compared to the positive control group (p=0.015). Although no significant
      difference (p=0.126) in the time of onset of viraemia could be detected between
      the groups of contact animals, a tendency towards the reduction of virus
      transmission was observed. Since sentinel animals were left untreated in this
      exploratory trial, the study can be regarded as a worst case scenario and gives
      therefore an underestimation of the potential efficacy of the activity of BPIP on
      virus transmission.

PMID- 19592180
TI  - Detection of a novel hemoplasma based on 16S rRNA gene DNA in captive and free
      ranging capybaras (Hydrochaeris hydrochaeris).
AB  - Two different species of hemoplasmas, Mycoplasma coccoides and M. haemomuris, are
      known to infect small rodents such as mice and rats. However, there are no
      previous reports of hemoplasma infection in capybara (Hydrochaeris hydrochaeris).
      The aim of our study was to determine whether these hemoplasmas might infect
      capybaras from Southern Brazil. Blood samples from 31 animals: 10 captive and 21
      free-ranging capybaras were collected and packed cell volume and total plasma
      protein were measured. DNA was extracted and PCR assays for M. coccoides and M.
      haemomuris were performed. Using the M. coccoides-PCR assay 64% of the capybaras
      were positive, 80% free-ranging and 30% from captive animals. The prevalence of
      infection between the groups was significantly different (p=0.001). Sequencing of
      the nearly entire 16S rRNA gene from the positive samples suggested a novel
      hemoplasma isolate with identity of 92% with M. coccoides and 86% with M.
      haemomuris. All capybara samples were negative for M. haemomuris infection. DNA
      of a housekeeping gene was successfully amplified from all samples. This is the
      first evidence of a hemoplasma infection in capybaras.

PMID- 19592181
TI  - PCR-AGE, automated and manual methods to identify Candida strains from veterinary
      sources: a comparative approach.
AB  - The increasing incidence of candidiasis has drawn the attention of scientists and
      clinicians attempting to improve methods of studying Candida yeasts. PCR
      amplification followed by agarose gel electrophoresis (PCR-AGE) and the manual
      method (morphological characteristics, biochemical profiles and culturing on
      CHROMagar-Candida) and VITEK 2 automated method were used to test a total of 30
      fungal strains from dog sources. The strains were obtained from cases of
      dermatitis, otitis externa and from the ears, oral mucosa, vaginal mucosa,
      prepuce and perianal region of clinically normal dogs. After identification as
      Candida yeasts by the manual method, the strains were analyzed using both VITEK
      and PCR-AGE methods. Isolates of C. parapsilosis ATCC 22019, C. krusei ATCC 6258
      and C. albicans ATCC 10231 were included as controls. The universal primers ITS1,
      ITS3 and ITS4 were used in two independent PCR reactions. Of 30 yeast isolates, 3
      isolates (Saccharomyces cerevisiae, C. rugosa and C. parapsilosis) that were
      incompletely identified by the manual method were identified with the PCR-AGE and
      VITEK methods. The results revealed a 96.7% and 86.7% concurrent identification
      between the PCR-AGE and VITEK methods versus the manual method, respectively. PCR
      AGE showed a greater level of concordance with the manual method, besides being
      faster and more sensitive than the other methods examined, and is therefore
      indicated for routine diagnostic testing of Candida spp. strains from veterinary
      sources.

PMID- 19592182
TI  - Influence of seminal plasma on fertility of fresh and frozen-thawed stallion
      epididymal spermatozoa.
AB  - The use of epididymal stallion spermatozoa for routine artificial insemination
      can secure easy future use of valuable genetics after unforeseen death or injury
      of a valuable stallion. The aims of this study were to (1) directly compare
      pregnancy rates for fresh and frozen-thawed stallion epididymal and ejaculated
      spermatozoa after conventional artificial insemination and (2) to investigate the
      effect of seminal plasma on the fertility of epididymal spermatozoa after
      insemination. Twenty-one mares were randomly assigned to three stallions. Mares
      were inseminated at five consecutive oestrous periods using fresh ejaculated
      spermatozoa (Fr-E, n=18), fresh epididymal spermatozoa that had been exposed to
      seminal plasma (Fr-SP+, n=12) or fresh epididymal spermatozoa that had never been
      exposed to seminal plasma (Fr-SP-, n=9), frozen-thawed ejaculated spermatozoa (Cr
      E, n=18), frozen-thawed epididymal spermatozoa that had been exposed to seminal
      plasma prior to freezing (Cr-SP+, n=18) and frozen-thawed epididymal spermatozoa
      that had never been exposed to seminal plasma (Cr-SP-, n=15). Pregnancy
      examinations were performed 14 days after each ovulation. Pregnancy rates were
      55.6% (Fr-E, 10/18), 75% (Fr-SP+, 9/12), 22.2% (Fr-SP-, 2/9), 38.9% (Cr-E, 7/18),
      27.8% (Cr-SP+, 5/18) and 6.7% (Cr-SP-, 1/15). Overall pregnancy rates for fresh
      and frozen-thawed epididymal spermatozoa that had been exposed to seminal plasma
      were significantly better than for epididymal spermatozoa that had never been
      exposed to seminal plasma (P<0.05). We conclude that the exposure of stallion
      epididymal spermatozoa to seminal plasma improves pregnancy rates.

PMID- 19592183
TI  - Effect of semen quality in transgenic boars on the developmental competence of
      preimplantation embryos.
AB  - The aim of this study was to compare the fertilising capacity of sperm from 6
      transgenic (TG) and 6 non-transgenic (NTG) boars based on analyses of embryos
      resulting from insemination with sperm from these particular boars. Expanded
      blastocysts were collected from five groups of synchronised gilts (six gilts per
      group) inseminated by TG boars bearing a gene construct containing the human
      alpha1,2-fucosyltransferase gene and by NTG boars. The ejaculates used for
      insemination were analysed to detect apoptotic changes using two fluorescence
      methods: an assay to assess early changes in the membrane integrity of the sperm
      using the YO-PRO-1 fluorophore and an assay for phosphatidylserine (PS)
      translocation across the plasma membranes using fluorescein-labelled Annexin-V.
      Our results, using a combination of YO-PRO-1 and PI fluorophores, revealed no
      significant differences in the percentage of sperm subpopulations between non
      transgenic and transgenic boars (P<0.01). Moreover, the second fluorescent probe
      also revealed no significant differences between the average values of live (Ann
      V(-)/PI(-)), early apoptotic (Ann-V(+)/PI(-)), and late apoptotic/early necrotic
      sperm (Ann-V(+)/PI(+)) as calculated for TG and NTG boars. Only the percentage of
      necrotic sperm (Ann-V(-)/PI(+)) was significantly different (P<0.05) between
      transgenic and non-transgenic boars (3.4%+/-2.7; 7.2%+/-2.1, respectively). The
      quality of the preimplantation embryos at the blastocyst stage was determined by
      counting the number of cells, observing a TUNEL-positive reaction and by caspase
      3 labelling. We found that expanded blastocysts that were derived from gilts
      inseminated with TG and NTG boar semen showed almost no DNA fragmentation (80%)
      and 70% caspase-3 activity. The expanded blastocysts that were derived from gilts
      inseminated with TG and NTG boar semen did not differ significantly in their DNA
      fragmentation, and there were no differences in caspase-3 activity. These results
      revealed a positive correlation between the percentage of blastocysts with TUNEL
      positive nuclei and the percentage of blastocysts with caspase-3 activity
      (r=0.9787; P<0.0001).

PMID- 19592184
TI  - Role of ethnicity in the expression of features of hot flashes.
AB  - The overall goal of this study was to determine the role of ethnicity on features
      of hot flashes (HFs) in a population of menopausal women in North Central Texas.
      A total of 397 ethnically diverse menopausal women from North Central Texas were
      administered our Menopausal Vasomotor Symptoms (MVS) survey to ascertain accurate
      information about number, length, intensity and behaviorally disruptive effects
      of hot flash episodes for subsequent analysis for the role of ethnicity in the
      occurrence of hot flashes. The mean (SD) age for participants was 50.2 (5.3)
      years; 40% were Caucasian, 38% were African-American and 22% were Hispanic. To
      evaluate and identify potential associations of hot flash (HF) features,
      ethnicity, and other independent variables, ordinal/multinomial/binary logistic
      regression models were used to calculate crude and adjusted odds ratios (ORs) and
      95% confidence intervals (CIs). The analysis demonstrates strong associations
      with ethnicity and the number of HF's/day, the length of each HF episode, the
      intensity of HFs, and the interruption of daily activities and sleep. Ethnicity
      was important in the crude and adjusted model describing the association between
      the number of HFs per day and ethnicity. African-American women were 2.22 (95%
      CI, 1.38-3.56) times and Hispanic women were 1.85 (95% CI, 1.08-3.18) times more
      likely to experience more frequent HFs per day than Caucasian women. In contrast,
      Hispanic women were less likely than Caucasian women to experience sweating and
      disruption of both daily activities and sleep. Collectively, our results show
      more frequent and more bothersome HFs in African-American women and more
      frequent, but less intense and bothersome HFs in Hispanic women in comparison to
      Caucasian women.

PMID- 19592185
TI  - Probabilistic evidential assessment of gunshot residue particle evidence (Part
      I): likelihood ratio calculation and case pre-assessment using Bayesian networks.
AB  - Well developed experimental procedures currently exist for retrieving and
      analyzing particle evidence from hands of individuals suspected of being
      associated with the discharge of a firearm. Although analytical approaches (e.g.
      automated Scanning Electron Microscopy with Energy Dispersive X-ray (SEM-EDS)
      microanalysis) allow the determination of the presence of elements typically
      found in gunshot residue (GSR) particles, such analyses provide no information
      about a given particle's actual source. Possible origins for which scientists may
      need to account for are a primary exposure to the discharge of a firearm or a
      secondary transfer due to a contaminated environment. In order to approach such
      sources of uncertainty in the context of evidential assessment, this paper
      studies the construction and practical implementation of graphical probability
      models (i.e. Bayesian networks). These can assist forensic scientists in making
      the issue tractable within a probabilistic perspective. The proposed models focus
      on likelihood ratio calculations at various levels of detail as well as case pre
      assessment.

PMID- 19592186
TI  - Digital mammography: an update.
AB  - Digital mammography has increasingly replaced conventional film-screen
      mammography and has become the gold standard in combination with soft copy
      reading in diagnostic as well as screening settings. Large international multi
      center trials were able to demonstrate at least equivalence and for some aspects
      superiority of digital over conventional mammography with regard to detectability
      of breast cancer, especially in pre/perimenopausal women, women younger than 50
      years and generally in dense breasts. Especially the experienced reader may
      benefit form CAD with an increase of specificity. Additionally digital
      mammography offers options of advanced processing such as digital tomosynthesis
      and contrast enhanced mammography. The future of breast imaging will be fusion of
      different imaging systems (hybrid systems).

PMID- 19592187
TI  - Cutaneous methicillin-resistant Staphylococcus aureus in a suburban community
      hospital pediatric emergency department.
AB  - BACKGROUND: Studies on methicillin-resistant Staphylococcus aureus (MRSA)
      infections have typically focused on pediatric and adult populations at urban
      tertiary care hospitals. Limited data exist on MRSA rates in skin and soft tissue
      infections (SSTI) in suburban community hospital pediatric emergency departments
      (PED). OBJECTIVES: To describe the prevalence of MRSA in SSTIs in a contemporary
      suburban community hospital PED population. METHODS: Patients 0-21 years old with
      SSTI wound cultures who were seen at our PED from 2003-2007 were studied. Data
      analyzed included type of infection (abscess vs. non-abscess), site of infection,
      and culture results. Chi-squared and t-tests were used as appropriate; p < 0.05
      was considered significant. RESULTS: During the study period, 204 cultures were
      obtained for SSTIs, 11 of which were contaminants. The subjects had a mean age of
      12.9 years (SD 6.8 years); 60% were male. The prevalence of MRSA was 27%; MRSA
      was present in 30% of abscesses vs. 2.2% of non-abscess SSTI (p < 0.005). By
      year, the prevalence of MRSA was 10% in 2003, 31% in 2004, 33% in 2005, 31% in
      2006, and 29% in 2007. No differences between MRSA and non-MRSA infections were
      present for gender, age, or site of infection. CONCLUSIONS: At our suburban
      community hospital pediatric ED, MRSA was present in 30% of all SSTI wound
      cultures; MRSA was unlikely with non-abscess SSTI. Our overall MRSA prevalence
      data among SSTIs are consistent with previously published reports in pediatric ED
      populations but may be less than those reported in the adult literature.

PMID- 19592188
TI  - Re: delays in transferring elderly trauma patients.

PMID- 19592190
TI  - A giant ruptured hydatid cyst causing tension pneumothorax and hemothorax in a
      patient with blunt thoracic trauma: a rare case encountered in the emergency
      clinic.

PMID- 19592191
TI  - Presenilin enhancer-2 (PSENEN), a component of the gamma-secretase complex, is
      involved in adipocyte differentiation.
AB  - This study was conducted to identify genes expressed during adipocyte
      differentiation of bovine intramuscular fibroblast-like cells using differential
      display reverse-transcriptase polymerase chain reaction. The presenilin enhancer
      2 (PSENEN) gene was found to be down-regulated during adipocyte differentiation
      of bovine intramuscular fibroblast-like cells. The ectopic expression of bovine
      PSENEN in 3T3-L1 reduced adipogenesis and the inhibition of endogenous PSENEN by
      siRNA induced adipogenesis on d 4 of adipocyte differentiation of 3T3-L1 cells.
      Interestingly, the expression of gamma-secretase complex gene-related Notch
      signaling was decreased at d 2 and d 4 during adipocyte differentiation. In
      addition, expression of the Notch-signaling genes (Notch-1, Hes-1, Pref-1,
      adipsin) was regulated during adipocyte differentiation by regulation of PSENEN
      expression. These results suggest that PSENEN plays an important role in
      adipocyte differentiation and that Notch signaling is involved in adipogenesis.

PMID- 19592192
TI  - Local regulation of corpus luteum development and regression in the cow: Impact
      of angiogenic and vasoactive factors.
AB  - The corpus luteum (CL) of the estrous cycle in the cow is a dynamic organ which
      has a life time of approximately 17-18 days. The main function of the CL is to
      secrete a large amount of progesterone (P) thereby supporting the achievement of
      pregnancy. As the CL matures, the steroidogenic cells establish contact with many
      capillaries and the matured CL is composed of many vascular endothelial cells
      that account for up to 50% of all CL cells. The bovine CL produces several major
      angiogenic and vasoactive foctors such as vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-1 and -2 (ANPT-1 and 
      2), prostaglandin F(2alpha) (PGF(2alpha)), endothelin-1 (EDN1), angiotensin II
      (Ang II) and nitric oxide (NO). These factors regulate P secretion directly
      and/or indirectly within the CL. Moreover, different actions of PGF(2alpha) in
      the early cycle CL (non-luteolytic) and the mid cycle CL (luteolytic) may provide
      insight into the luteolysis cascade in the cow. The aim of the present review is
      to describe the current concepts of the local mechanisms for the cascade of
      development and regression of the bovine CL as regulated by luteal angiogenic and
      vasoactive factors.

PMID- 19592193
TI  - Clinical success using patient-oriented outcome measures after lower extremity
      bypass and endovascular intervention for ischemic tissue loss.
AB  - INTRODUCTION: Successful outcome after lower extremity revascularization is
      usually measured by physician-oriented terms such as graft patency and amputation
      free survival. It has been increasingly appreciated that these criteria do not
      necessarily translate into success from the prospective of the patient. The
      purpose of this study, therefore, is to retrospectively examine success after
      lower extremity revascularization for tissue loss using patient-oriented measures
      and to include patients who underwent both open surgical bypass and endovascular
      therapy. METHODS: Between 1998 and 2005, 677 patients (316 endovascular and 361
      open surgery) underwent revascularization for ischemic tissue loss. The method of
      revascularization (endovascular or open surgery) was left to the discretion of
      the surgeon. Revascularization was considered to be clinically successful if each
      of the following occurred: reconstruction patency until wound healing, limb
      salvage for 1 year, maintenance of ambulation for 1 year, and survival for 6
      months. The influence of 20 intrinsic patient factors, including type of
      revascularization (open vs endo) was examined using the chi(2) test. Significant
      factors in bivariate analysis were included in a logistic regression model to
      determine independent predictors and probability of failure. RESULTS: Overall
      clinical success was achieved in 277 (40.9%) patients. Success for open surgical
      and endovascular cohorts was 44.3% and 37.0%, respectively (P = .06). Type of
      intervention was not a significant factor in either bivariate or logistic
      regression analysis. Independent predictors of failure (odds ratio [OR]; 95%
      confidence interval [CI]) regardless of treatment type included impaired
      ambulatory status at the time of presentation (OR 3.24; CI 2.14, 4.90), diabetes
      (OR 1.62; CI 1.14, 2.32), endstage renal disease (ESRD) (OR 1.55; CI 1.07, 2.23),
      presence of gangrene (OR 2.0; CI 1.42, 2.82), and prior vascular intervention (OR
      1.46; CI 1.02, 2.10). Paradoxically, hyperlipidemia (OR 0.70; CI 0.50, 0.98) was
      a predictor for success. Probability of failure was 35.4% (OR 1.0) if no
      independent predictors were present and increased with the addition of each
      adverse predictor. For instance, diabetic patients with impaired ambulatory
      status and gangrene had an 85.2% (OR 10.5) probability of failure. In the worst
      case scenario, a diabetic patient with ESRD, impaired ambulatory status,
      gangrene, and a prior vascular intervention was considered, probability of
      failure was a dismal 92.8% (OR 23.7). CONCLUSION: Clinical success after lower
      extremity revascularization for ischemic tissue loss is determined by intrinsic
      patient factors and not by method of revascularization. These data reiterate that
      future investigation efforts should be focused less on the method of
      revascularization and more on identification of patient cohorts at risk for
      failure regardless of treatment.

PMID- 19592195
TI  - Intramammary lymph node metastasis of breast cancer after sentinel node biopsy:
      two cases and a review of the literature.

PMID- 19592196
TI  - [Severe head trauma: main targets of the intensive care phase].

PMID- 19592197
TI  - [A case of cutaneous and mucous haemorrhage secondary to vitamin K deficiency in
      hyperemesis gravidarum].
AB  - The frequency of the syndrome of hyperemesis gravidarum (HG) varies from 0.1 to
      2% according to the literature. The complications are generally benign. Some of
      them can compromise the life outcome. Only two cases of HG with bleeding disorder
      (major epitasis) related to a vitamin K deficiency were previous reported. Here
      is described a third case related to a vitamin deficiency K. It is characterized
      by a skin and mucosa haemorrhage (gingivorrhagias; bleeding in urine; bruises at
      the points of puncture) and by the necessity to treat her in emergency with fresh
      frozen plasma before intravenous vitamin K as soon as the diagnosis of vitamin K
      deficiency was done. The indication of the use of frozen fresh plasma is
      discussed.

PMID- 19592198
TI  - [Is it time to have more devices for difficult intubation available to the
      emergency mobile services?].

PMID- 19592199
TI  - [False capillary hyperglycaemia and true iatrogenic postoperative hypoglycaemia].
AB  - We describe a case-report of a 64-year-old woman who presented an acute
      iatrogenic hypoglycaemia after gynecological surgery. An inadequate keeping of
      Dextrostix led to wrong hyperglycaemia measurement and inappropriate insulin
      administration. The mistake was treated with complete recovery.

PMID- 19592200
TI  - Constipation in intensive care unit: incidence and risk factors.
AB  - PURPOSE: Although gastrointestinal motility disorders are common in critically
      ill patients, constipation and its implications have received very little
      attention. We aimed to determine the incidence of constipation to find risk
      factors and its implications in critically ill patients MATERIALS AND METHODS:
      During a 6-month period, we enrolled all patients admitted to an intensive care
      unit from an universitary hospital who stayed 3 or more days. Patients submitted
      to bowel surgery were excluded. RESULTS: Constipation occurred in 69.9% of the
      patients. There was no difference between constipated and not constipated in
      terms of sex, age, Acute Physiology and Chronic Health Evaluation II, type of
      admission (surgical, clinical, or trauma), opiate use, antibiotic therapy, and
      mechanical ventilation. Early (<24 hours) enteral nutrition was associated with
      less constipation, a finding that persisted at multivariable analysis (P < .01).
      Constipation was not associated with greater intensive care unit or mortality,
      length of stay, or days free from mechanical ventilation. CONCLUSIONS:
      Constipation is very common among critically ill patients. Early enteral
      nutrition is associated with earlier return of bowel function.

PMID- 19592201
TI  - Mortality reduction after implementing a clinical practice guidelines-based
      management protocol for severe traumatic brain injury.
AB  - INTRODUCTION: The objective of this study was to examine the effect of
      implementing a clinical practice guidelines-based management protocol on the
      outcome of patients with severe traumatic brain injury (TBI). METHODS: We carried
      out a pre-post guideline implementation study using previously collected data in
      the Intensive Care Unit (ICU). All patients older than 12 years with severe TBI,
      defined as a Glasgow Coma Scale score of 8 or less, from March 1999 to January
      2001 (control group) and from February 2001 to December 2006 (protocol group)
      were identified and included in this study. Patients in the protocol group were
      managed using a clinical practice guidelines-based management protocol, derived
      from the guidelines published by the Brain Trauma Foundation. Primary outcome was
      hospital mortality, whereas the secondary outcome was ICU mortality. To assess
      whether the ICU protocol might have led to an increase in the number of surviving
      patients with severe disability, we examined the association of the protocol use
      and the need for tracheostomies, mechanical ventilation duration, and ICU and
      hospital length of stay (LOS) among survivors. RESULTS: During the study period,
      a total of 434 patients met the inclusion criteria. After adjustment for several
      prognostic factors, the use of protocol was independently associated with a
      significant reduction in hospital and ICU mortality (odds ratio, 0.45; 95%
      confidence interval, 0.24-0.86; and odds ratio, 0.47; 95% confidence interval,
      0.23-0.96, respectively). The use of the protocol was not associated with an
      increase in the need for tracheostomies, mechanical ventilation duration, ICU
      LOS, and hospital LOS. CONCLUSION: The protocol implementation was associated
      with a reduction in hospital and ICU mortality. This improvement was not
      associated with an increase in the frequency of tracheostomies and in ICU or
      hospital LOS, suggesting that the improved survival was not associated with the
      increased number of surviving patients with severe disability and that the
      functional status might have also improved.

PMID- 19592202
TI  - A randomized controlled trial comparing a computer-assisted insulin infusion
      protocol with a strict and a conventional protocol for glucose control in
      critically ill patients.
AB  - PURPOSE: The objective of this study is to evaluate blood glucose (BG) control
      efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU)
      patients. METHODS: This was a multicenter randomized controlled trial involving
      167 MICU patients with at least one BG measurement >or=150 mg/dL and one or more
      of the following: mechanical ventilation, systemic inflammatory response
      syndrome, trauma, or burns. The interventions were computer-assisted insulin
      protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL;
      Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or
      conventional treatment-subcutaneous insulin if glucose >150 mg/dL. The main
      efficacy outcome was the mean of patients' median BG, and the safety outcome was
      the incidence of hypoglycemia (<or=40 mg/dL). RESULTS: The mean of patients'
      median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional
      treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs
      conventional). In CAIP, 12 patients (21.4%) had at least one episode of
      hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P =
      .02, CAIP vs Leuven; P = .006, CAIP vs conventional). CONCLUSIONS: The CAIP is
      safer than and as effective as the standard strict protocol for controlling
      glucose in MICU patients. Hypoglycemia was rare under conventional treatment.
      However, BG levels were higher than with IV insulin protocols.

PMID- 19592203
TI  - Biosignal analysis techniques for weaning outcome assessment.
AB  - Discontinuation of mechanical ventilation in critically ill patients is a
      challenging task and involves a careful weighting of the benefits of early
      extubation and the risks of premature spontaneous breathing trial. Recently,
      apart from studying different physiological variables by means of descriptive
      statistical tests, breathing pattern variability analysis has been performed for
      the assessment of weaning readiness. A limited number of clinical studies
      implementing different weaning protocols in heterogeneous groups of patients and
      using a variable set of signal processing techniques have appeared in the
      critical care literature, with varying results. The purpose of this review
      article is 3-fold: (1) to describe the different signal processing techniques
      being implemented for the assessment of weaning readiness, (2) to provide insight
      into the pathophysiological mechanisms that may govern breath-to-breath
      variability/complexity in health and disease, and (3) to present results from the
      critical care literature derived from the application of biosignal analysis tools
      for the identification of possible weaning indices.

PMID- 19592204
TI  - Severe respiratory failure due to diffuse alveolar hemorrhage: clinical
      characteristics and outcome of intensive care.
AB  - BACKGROUND: The aim of this study was to characterize patients and report outcome
      of diffuse alveolar hemorrhage (DAH) requiring intensive care unit support.
      PATIENTS AND METHODS: Thirty-seven patients were identified. Clinical
      characteristics and outcome were determined by chart review. RESULTS: Eighty-nine
      percent of patients presented with shortness of breath, 23% with cough, and 3%
      with hemoptysis. In 9% of patients, a diagnosis of DAH was suspected on
      admission. Diagnosis was confirmed by finding a progressively hemorrhagic
      bronchoalveolar lavage fluid in 89% and by a positive iron stain in 11% of
      patients. Vasculitis was causative in 19%, drug toxicity in 11%, thrombocytopenia
      in 27%, stem-cell transplantation in 5%, sepsis-associated lung injury in 22%,
      and unknown mechanisms in 16%. Thirty-two patients were mechanically ventilated,
      4 received noninvasive ventilation, and 1 received supplemental oxygen therapy.
      Overall, 18 (49%) of 37 patients survived the intensive care unit stay. Survival
      was markedly different between patients with an immunologic/unknown etiology
      (82%) and patients with thrombocytopenia and/or sepsis (22%). DISCUSSION: Diffuse
      alveolar hemorrhage should be considered in all patients with persistent
      pulmonary infiltrates. Both bronchoalveolar lavage fluid and iron stain are
      mandatory diagnostic means. Patients with an immunologic/idiopathic pathogenetic
      mechanism have a relatively good prognosis, whereas the outcome in individuals
      with DAH secondary to cancer therapy or sepsis is poor.

PMID- 19592205
TI  - Bronchopleural fistula: an update for intensivists.
AB  - Bronchopleural fistula is a potentially fatal condition that may result after a
      variety of clinical conditions, most commonly after pulmonary resection. Either
      surgical or bronchoscopic repair is required to definitively correct these
      lesions, though a small number may resolve spontaneously with optimal ventilatory
      care and other options available to an intensivist in the management of this
      complex condition. The successful management of a bronchopleural fistula depends
      on formulating a treatment strategy tailored to individual patient needs.

PMID- 19592206
TI  - Epoetin alfa reduces blood transfusion requirements in patients with
      intertrochanteric fracture.
AB  - PURPOSE: The purpose of this study is to identify the potential benefits or
      complications from the use of epoetin alfa in patients with intertrochanteric
      fracture. MATERIALS AND METHODS: Seventy-nine patients who sustained an
      intertrochanteric fracture were divided into 2 groups. One group received 10
      daily doses of 20 000 IU of epoetin alfa beginning from the day of trauma,
      whereas the control group received placebo. RESULTS: We found a statistically
      significant difference in the required units of allogenic blood used between the
      2 groups (P = .034). The group that received epoetin alfa also showed an
      elevation of hematocrit and hemoglobin values, which was statistically
      significant at the seventh postoperative day (P = .019 and .015, respectively)
      compared to the control group. No complications were evident during our study.
      CONCLUSIONS: Patients with intertrochanteric fractures seem to benefit from the
      use of epoetin alfa because it is safe and reduces the need for blood
      transfusions.

PMID- 19592207
TI  - Risk factors for the deterioration of oxygenation ratio in ventilated intensive
      care unit patients: a retrospective cohort study.
AB  - PURPOSE: The aim of the study is to determine which factors are associated with
      the deterioration of Pao(2)/fraction of inspired oxygen (Fio(2)) ratio in
      patients with normal oxygenation at admission and ventilated according to a lung
      protective ventilation strategy. MATERIALS AND METHODS: Retrospective cohort
      study of ventilated (>/=3 days) intensive care unit patients with an admission
      Pao(2)/Fio(2) ratio of 300 mm Hg or higher (n = 105). Patients who developed lung
      injury (Pao(2)/Fio(2) ratio, <300 mm Hg) on day 7 (n = 37) were compared to those
      who did not (n = 68), with regard to ventilator settings, gas exchange variables,
      and lung injury risk factors. RESULTS: Mean +/- SD of administered tidal volume
      was 7.9 +/- 1.3 mL/kg. Patients who developed lung injury were older (P = .019),
      had lower Pao(2) (P = .009), higher Paco(2) (P = .045), and lower Pao(2)/Fio(2)
      ratio (P = .002) at admission. Postoperative state (Hazard risk [HR], 5.1) and
      controlled ventilation mode (HR, 4.3) were identified as independent risk
      factors. Lung injury-free time was shorter in patients with low initial
      Pao(2)/Fio(2) ratio (odds ratio, 1.7; P = .039). This effect was not only caused
      by the baseline difference, as the decrease in Pao(2)/Fio(2) ratio was more
      pronounced in patients who developed lung injury compared to those who did not (P
      = .008). CONCLUSIONS: Lung injury exacerbates during mechanical ventilation. In
      patients treated with a mean tidal volume of 7.9 mL/kg, controlled ventilation is
      a major risk factor.

PMID- 19592208
TI  - Systemic and bronchoalveolar cytokines as predictors of in-hospital mortality in
      severe community-acquired pneumonia.
AB  - OBJECTIVES: The aim of this study was to determine whether cytokine expression
      (interleukin [IL]-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]
      alpha), C-reactive protein, and endotoxins on the first day of intensive care
      unit (ICU) admission are associated with hospital mortality in severe community
      acquired pneumonia (CAP). DESIGN: This was a prospective study with
      bronchoalveolar lavage (BAL) and blood sampling. SETTING: This study was carried
      out in a 44-bed medical ICU of a 1700-bed university hospital. PATIENTS:
      Participants included 112 mechanically ventilated patients with severe CAP.
      INTERVENTIONS: Serum and BAL fluid IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, C
      reactive protein, and endotoxins on the first day of ICU admission were obtained.
      MEASUREMENTS AND MAIN RESULTS: The concentrations of TNF-alpha in BALF and IL-6,
      IL-8, IL-10, and TNF-alpha in serum were higher in nonsurvivors than in survivor
      patients with CAP. Of these 112 patients with severe CAP (39%), 44 developed
      acute respiratory distress syndrome (ARDS); these patients seemed to have higher
      serum IL-6, IL-8, and IL-10 levels than did the non-ARDS group. Furthermore, in
      the ARDS population, we found that the endotoxin levels in the BAL fluid were
      higher in the survival than in the nonsurvival group and BAL fluid concentrations
      of IL-6, IL-8, and IL-1beta and sera levels of IL-6 and IL-10 were lower in the
      survival than in the nonsurvival group, and they were associated with a high
      negative predictive value. CONCLUSIONS: Serum and BAL fluid levels of the studied
      cytokines on admission may provide valuable prognostic information for patients
      with severe CAP.

PMID- 19592209
TI  - Accuracy of clinical definitions of ventilator-associated pneumonia: comparison
      with autopsy findings.
AB  - METHODS: We studied patients requiring mechanical ventilation for more than 48
      hours who died in the intensive care unit and whose bodies were autopsied. We
      evaluated 3 clinical definitions of ventilator-associated pneumonia: loose
      definition, defined as chest radiograph infiltrates and 2 of 3 clinical criteria
      (leukocytosis, fever, purulent respiratory secretions); rigorous definition,
      defined as chest radiograph infiltrates and all of the clinical criteria; and a
      clinical pulmonary infection score higher than 6 points. Sensitivity,
      specificity, and likelihood ratios were calculated by using pathology pattern as
      criterion standard. RESULTS: One hundred forty-two (56%) of the 253 patients
      included had histological criteria of pneumonia. Patients who met the clinical
      criteria of ventilator-associated pneumonia were 163 (64%) for the loose
      definition, 32 (13%) for the rigorous definition, and 109 (43%) for the clinical
      pulmonary infection score. The operative indexes (sensitivity and specificity) of
      each definition were as follows: loose definition, 64.8% and 36%; rigorous
      definition, 91% and 15.5%; and clinical pulmonary infection score higher than 6,
      45.8% and 60.4%. The addition of microbiological data to the clinical definitions
      increased the specificity and decreased the sensitivity but not significantly.
      CONCLUSIONS: Accuracy of 3 commonly used clinical definitions of ventilator
      associated pneumonia was poor taking the autopsy findings as reference standard.

PMID- 19592210
TI  - Investigation of critical care unit utilization and mortality in patients
      infected with Clostridium difficile.
AB  - BACKGROUND: A nationwide increase in the rate and severity of Clostridium
      difficile-associated disease may reflect infection with a virulent strain
      characterized by polymerase chain reaction as ribotype 027 (NAP1/B1). HYPOTHESIS:
      The high prevalence of ribotype 027 at our institution would allow investigation
      of the risk of mortality and admission to the intensive care unit (ICU)
      associated with C difficile infection. METHODS: In a retrospective cohort study,
      we identified 108 patients with positive enzyme-linked immunosorbant assay tests
      for C difficile toxins over a 6-month period and compared them to 108 patients
      who were suspected to have C difficile but with negative toxin assays.
      Proportions of all-cause mortality and ICU admission were compared using chi(2),
      and odds ratios (ORs) were estimated using logistic regression to adjust for
      potential confounders. Mean log lengths of stay were compared using t test.
      RESULTS: Comparing patients with C difficile to those without, mortality (20% vs
      8%) and ICU admission (32% vs 17%) were significantly higher (P = .02 for both),
      whereas log length of stay was not (P = .29). Adjusting for potential
      confounders, the OR for mortality was 6.8 (95% confidence interval, 1.8-25.4; P =
      .01), whereas for ICU admission, the association was no longer observed (OR, 1.0;
      95% confidence interval, 0.4-2.5; P = .97). CONCLUSION: C difficile infection was
      associated with increased all-cause mortality. An observed association with ICU
      admission and C difficile infection was identified through univariate analysis
      but was not significant in multivariate analysis. Although we did not strain-type
      isolates for patients infected with C difficile, the institutional prevalence of
      ribotype 027 C difficile infection was known to be high. These results document a
      strong association between ribotype 027 C difficile infection and mortality and
      underscore the need to identify effective C difficile preventive strategies.

PMID- 19592212
TI  - Actigraphic monitoring in critically ill patients: preliminary results toward an
      "observation-guided sedation".
AB  - PURPOSE: The aim of this study is to evaluate continuous wrist actigraphy
      (measurement of limb movements) in intensive care unit patients as a neurologic
      status monitoring. MATERIALS AND METHODS: This is a prospective, observational
      study on motor activity of adult patients using wrist actigraphs. Nurses recorded
      the number of sleep and agitation hours as well as assessed pain and anxiety
      level (verbal numeric rating) and the agitation/sedation level (Richmond
      Agitation-Sedation Scale). RESULTS: Thirteen mechanically ventilated patients
      were studied during their whole intensive care unit stay (total, 165 patients/d).
      The number of surveyed movements was gathered for each hour, obtaining an
      estimation of patient motor status. This measure was different between days and
      nights (33.3 [20.3-49.0] vs 8.5 [4.4-13.8]; P < .001), with a correlation with
      sleeping hours estimated by nurses (P = .017 during the days [D], P < .001 during
      the nights [N]), agitation hours (P = .002 D, P = .017 N), Richmond Agitation
      Sedation Scale value (P < .001 D and N), pain (P = .012 D), and anxiety (P < .001
      D) verbal numeric rating. No differences were found using epochs of 15 or 120
      seconds. Compliance with patients and nurses was acceptable. CONCLUSIONS:
      Patients' limb movements were significantly related to all studied neurologic
      status indexes. Continuous actigraphy measuring may become important as a
      clinical tool both to guide utilization of sedative drugs and to enhance early
      recognition and management of agitation.

PMID- 19592211
TI  - Effect of frequency of ventilator circuit changes (3 vs 7 days) on the rate of
      ventilator-associated pneumonia in PICU.
AB  - PURPOSE: Ventilator-associated pneumonia (VAP) is associated with significant
      morbidity and mortality in pediatric intensive care unit (PICU). Our purpose was
      to evaluate the effects of ventilator circuit change on the rate of VAP in the
      PICU. METHODS: A prospective randomized controlled trial was conducted at a
      university hospital PICU. Children (younger than 18 years) who received
      mechanical ventilation from December 2006 to November 2007 were randomly assigned
      to receive ventilator circuit changes every 3 or 7 days. RESULTS: Of 176
      patients, 88 were assigned to receive ventilator circuit every 3 days and 88
      patients had a change weekly. The rate of VAP was 13.9/1000 ventilator days for
      the 3-day circuit change (n = 12) vs 11.5/1000 ventilator days (n = 10) for the 7
      day circuit change (odds ratio, 0.8; confidence interval, 0.3-1.9; P = .6). There
      was a trend toward decreased PICU stay and mortality rate in 7-day change group
      compared to 3-day change group but did not reach statistical significance.
      Furthermore, switching from a 3-day to a 7-day change policy could save costs up
      to US $22,000/y. CONCLUSIONS: The 7-day ventilator circuit change did not
      contribute to increased rates of VAP in our PICU. Thus, it may be used as a guide
      to save workload and supply costs.

PMID- 19592213
TI  - Imipenem-resistant Pseudomonas aeruginosa infection at a medical-surgical
      intensive care unit: risk factors and mortality.
AB  - OBJECTIVES: The aim of this study was to evaluate the risk factors and
      attributable mortality associated with imipenem-resistant Pseudomonas aeruginosa
      (IRPA) infections in a medical-surgical intensive care unit (ICU). METHODS: A
      retrospective case-control study was carried out at a 16-bed medical-surgical ICU
      in a 780-bed, university-affiliated hospital. All patients admitted from January
      1, 2003, to December 31, 2004, who had nosocomial infection caused by IRPA, were
      included in the study. RESULTS: Imipenem-resistant P. aeruginosa was recovered
      from 63 patients during the study period. One hundred eighty-two controls were
      matched with cases by period of admission, age, and time at risk. Urinary tract
      (34.9%) and respiratory tract (22.2%) were the main sources of IRPA isolation. In
      multivariate analysis, a previous stay in the ICU (odds ratio, 3.54; 95%
      confidence interval [CI], 1.29-9.73; P = .03) was the only independent risk
      factor for IRPA infection. The in-hospital mortality rate among case patients was
      49% (31 of 63) compared with 33% (61 of 182) for control patients (odds ratio,
      1.92; 95% CI, 1.07-3.44; P = .02). Thus, we had an attributable mortality of 16%
      (95% CI, 9.74%-22.3%; P = .03). CONCLUSIONS: Our study suggests that IRPA
      infections are strongly related to previous ICU stay, and that IRPA infections
      significantly increase mortality in those critical patients.

PMID- 19592215
TI  - Subspace-based support vector machines for pattern classification.
AB  - In this paper, we discuss subspace-based support vector machines (SS-SVMs), in
      which an input vector is classified into the class with the maximum similarity.
      Namely, for each class we define the weighted similarity measure using the
      vectors called dictionaries that represent the class, and optimize the weights so
      that the margin between classes is maximized. Because the similarity measure is
      defined for each class, for a data sample the similarity measure to which the
      data sample belongs needs to be the largest among all the similarity measures.
      Introducing slack variables, we define these constraints either by equality
      constraints or inequality constraints. As a result we obtain subspace-based least
      squares SVMs (SSLS-SVMs) and subspace-based linear programming SVMs (SSLP-SVMs).
      To speedup training of SSLS-SVMs, which are similar to LS-SVMs by all-at-once
      formulation, we also propose SSLS-SVMs by one-against-all formulation, which
      optimize each similarity measure separately. Using two-class problems, we clarify
      the difference of SSLS-SVMs and SSLP-SVMs and evaluate the effectiveness of the
      proposed methods over the conventional methods with equal weights and with
      weights equal to eigenvalues.

PMID- 19592214
TI  - Retrospective reports of behavioral inhibition and young adults' current symptoms
      of social anxiety, depression, and anxious arousal.
AB  - The primary goal of this study was to investigate the specificity of the social
      versus nonsocial components of self-reported behavioral inhibition during
      childhood with young adults' current symptoms of anhedonic depression, social
      anxiety, and anxious arousal. As hypothesized, the social component of BI
      demonstrated some specificity for symptoms of social anxiety versus other
      internalizing disorders. Furthermore, results support the hypothesis that the
      relationship between BI and depressive symptoms is mediated by levels of social
      anxiety and anxious arousal.

PMID- 19592216
TI  - Synchronization of nonidentical chaotic neural networks with time delays.
AB  - The synchronization problem is studied in this paper for nonidentical chaotic
      neural networks with time delays, where the mismatched parameters are taken into
      account. An integral sliding mode control approach is proposed to address it. As
      a first step, a proper sliding surface is constructed. Based on the drive
      response concept and Lyapunov stability theory, both delay-independent and delay
      dependent conditions are derived under which the resulting error system is
      globally asymptotically stable in the specified switching surface. The gain
      matrix of the sliding mode is achieved by means of a linear matrix inequality,
      which can be solved by resorting to standard numerical algorithm. Then, a sliding
      mode controller is synthesized to guarantee the reachability of the specified
      sliding surface. A simulation example is finally exploited to illustrate the
      effectiveness of the developed approach.

PMID- 19592217
TI  - RKF-PCA: robust kernel fuzzy PCA.
AB  - Principal component analysis (PCA) is a mathematical method that reduces the
      dimensionality of the data while retaining most of the variation in the data.
      Although PCA has been applied in many areas successfully, it suffers from
      sensitivity to noise and is limited to linear principal components. The noise
      sensitivity problem comes from the least-squares measure used in PCA and the
      limitation to linear components originates from the fact that PCA uses an affine
      transform defined by eigenvectors of the covariance matrix and the mean of the
      data. In this paper, a robust kernel PCA method that extends the kernel PCA and
      uses fuzzy memberships is introduced to tackle the two problems simultaneously.
      We first introduce an iterative method to find robust principal components,
      called Robust Fuzzy PCA (RF-PCA), which has a connection with robust statistics
      and entropy regularization. The RF-PCA method is then extended to a non-linear
      one, Robust Kernel Fuzzy PCA (RKF-PCA), using kernels. The modified kernel used
      in the RKF-PCA satisfies the Mercer's condition, which means that the derivation
      of the K-PCA is also valid for the RKF-PCA. Formal analyses and experimental
      results suggest that the RKF-PCA is an efficient non-linear dimension reduction
      method and is more noise-robust than the original kernel PCA.

PMID- 19592219
TI  - Induction of non-alcoholic fatty liver disease and insulin resistance by feeding
      a high-fat diet in rats: does coenzyme Q monomethyl ether have a modulatory
      effect?
AB  - OBJECTIVE: The aim of this study was to investigate the development of non
      alcoholic fatty liver disease (NAFLD) in response to a high-fat diet in rats and
      to test the hypothesis that dietary coenzyme Q monomethyl ether (CoQme) has
      antisteatogenic effects. METHODS: Rats were fed a standard low-fat diet (control)
      for 18 wk or a diet containing 35% fat (57% metabolizable energy) for 10 wk, then
      divided into three groups for the following 8 wk. One group was given CoQ9me
      (30mg/kg body weight per day in 0.3mL olive oil: high fat+CoQ9me), the second
      olive oil (0.3mL/d) only (high fat + olive oil), and the third group received no
      supplements (high fat). RESULTS: Insulin levels and the activity of alanine
      aminotransferase in the plasma were significantly increased in all high-fat diet
      groups, and the homeostasis model assessment of insulin resistance indicated
      insulin resistance. Triacylglycerol concentrations in whole plasma and in very
      low-density lipoprotein and low-density lipoprotein fractions were also raised.
      Liver histology showed lipid accumulation in animals fed the high-fat diets, and
      liver triacylglycerol levels were increased (2.5- to 3-fold) in all high-fat diet
      groups. These effects were not changed by the administration of CoQ9me.
      CONCLUSIONS: Rats fed a diet with 57% energy from fat showed insulin resistance,
      hypertriglyceridemia, increased very low-density lipoprotein production, hepatic
      steatosis, and liver damage, and thus provide a good model for the early stages
      of NAFLD. Dietary CoQ9me, however, did not ameliorate the damaging effects of the
      high-fat diet.

PMID- 19592218
TI  - Computational perspectives on forebrain microcircuits implicated in reinforcement
      learning, action selection, and cognitive control.
AB  - Abundant new information about signaling pathways in forebrain microcircuits
      presents many challenges, and opportunities for discovery, to computational
      neuroscientists who strive to bridge from microcircuits to flexible cognition and
      action. Accurate treatment of microcircuit pathways is especially critical for
      creating models that correctly predict the outcomes of candidate neurological
      therapies. Recent models are trying to specify how cortical circuits that enable
      planning and voluntary actions interact with adaptive subcortical microcircuits
      in the basal ganglia. The basal ganglia are strongly implicated in reinforcement
      learning, and in all behavior and cognition over which the frontal lobes exert
      flexible control. The persisting role of the basal ganglia shows that ancient
      vertebrate designs for motivated action selection proved adaptable enough to
      support many "modern" behavioral innovations, including fluent generation of
      language and speech. This paper summarizes how recent models have incorporated
      realistic representations of microcircuit features, and have begun to trace their
      computational implications. Also summarized are recent empirical discoveries that
      provide guidance regarding how to formulate the rules for synaptic modification
      that govern learning in cortico-striatal pathways. Such efforts are contributing
      to an emerging synthesis based on an interlocking set of computational hypotheses
      regarding cortical interactions with basal ganglia and thalamic nuclei. These
      hypotheses specify how specialized microcircuits solve learning and control
      problems inherent to the brain's parallel design.

PMID- 19592221
TI  - Effects of deep-frying oil on blood pressure and oxidative stress in
      spontaneously hypertensive and normotensive rats.
AB  - OBJECTIVE: Ingestion of deep-frying oil has been reported to cause physiologic
      and histologic changes in experimental animals' tissue, increase the oxidative
      stress, and possibly lead to death. The purpose of this study was to investigate
      the effect of deep-frying oil on oxidative stress and blood pressure in
      spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. METHODS: Deep
      frying oil was prepared by frying fresh soybean oil at 180 +/- 5 degrees C for 8
      h each day, for 4 consecutive days. Male SHR and WKY rats were fed diets
      containing 15% fresh soybean oil or deep-frying oil (DO) for 10 wk. RESULTS: Rats
      ingesting the DO diet had lower feed efficiency and higher relative liver and
      kidney weights but deep frying had no significant influence on blood pressure in
      WKY or SHR rats. The DO diet had no effect on plasma renin activity, aldosterone
      content, or tissue angiotension-I-converting enzyme activity. WKY rats fed the DO
      diet showed significantly increased urinary thromboxane B(2) and 8-iso
      prostaglandin F(2alpha) excretion, but not urinary 6-keto-prostaglandin F(1alpha)
      excretion. Diets containing deep-frying oil resulted in increased plasma
      thiobarbituric acid-reactive substances and nitric oxide contents and decreased
      plasma total antioxidant capacity in SHR and WKY rats. CONCLUSION: The ingestion
      of deep-frying oil seemed not to influence blood pressure or its related
      parameters, but altered eicosanoid metabolism and elevated oxidative stress in
      SHR and WKY rats.

PMID- 19592220
TI  - Obesity and its associations with hypertension and type 2 diabetes among Chinese
      adults age 40 years and over.
AB  - AIM: To investigate the prevalence of obesity in a Chinese community according to
      the World Health Organization recommended criteria for Asians in 2000 based on
      body mass index (BMI) and waist circumference (WC), and to examine the
      associations between obesity and the risk of hypertension and type 2 diabetes
      among adults age 40 years and over in Shanghai, China. METHODS: A population
      based survey was conducted in Youyi Community in Shanghai. Five thousand seventy
      one subjects (1917 men and 3154 women) were included in this study. Standard
      questionnaires were used to collect baseline data of participants. Body weight,
      height, WC, blood pressure, and glucose in the blood were measured. RESULTS: The
      prevalence of general obesity was 44.6% (46.4% for men and 43.6% for women)
      according to BMI and 36.1% (25.5% for men and 42.6% for women) for central
      obesity according to WC. The prevalence of obesity I was higher in men (41.6%)
      than in women (36.2%; chi(2) =14.8, P<0.05), although the rate was higher in
      women than in men for obesity II (7.4% versus 4.8%, chi(2) =13.6, P<0.01) or
      central obesity (42.6% versus 25.5%, chi(2) =152.1, P<0.01). Odds ratios of
      hypertension and type 2 diabetes were significantly higher in the obesity group
      compared with either the group with BMI 18.5-<23.0kg/m(2) or the group with
      WC<90cm for men or <80cm for women. CONCLUSIONS: According to the criteria of
      obesity for Asians, the prevalence of obesity among Chinese adults age 40 years
      and over in Shanghai is high. Subjects with obesity have a significantly higher
      risk of hypertension and type 2 diabetes.

PMID- 19592222
TI  - Concordance with dietary and lifestyle population goals for cancer prevention in
      Dutch, Scottish, Mexican, and Guatemalan population samples.
AB  - OBJECTIVES: We assessed concordance with selected population goal components of
      the 1997 World Cancer Research Fund/American Institute for Cancer Research
      (WCRF/AICR) diet and lifestyle recommendations to decrease cancer risk across
      four population samples. METHODS: This was a prospectively designed survey
      examining concordance with the population goals of the WCRF/AICR recommendations
      using target criteria across sites. Population samples were from the Netherlands,
      Scotland, Mexico, and Guatemala. A total of 3564 men and women aged 18 to 70 y
      were recruited in equal proportions by site and gender. RESULTS: None of the four
      pooled samples met the target population average criteria for body mass index or
      refined sugar intake. The Guatemalan sample had concordance with the largest
      number of recommended cancer-prevention goals (10 of 12 selected WCRF/AICR
      components). Successively, Mexican, Scottish, and Dutch samples were concordant
      with seven, four, and three selected components, respectively. CONCLUSIONS: A
      prospectively designed research instrument and exhaustive prior examination of
      operative criteria allow for the assessment of group-level concordance with
      cancer-prevention goals. To the extent that the study samples reflect the
      respective national situations, geographic variance in concordance exists, with
      conditions and behaviors in Guatemala bringing that nation into more general
      compliance with the 1997 WCRF/AICR goals.

PMID- 19592223
TI  - Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter
      randomized, controlled trial.
AB  - OBJECTIVE: Very-low-calorie diets (VLCDs) are an effective method for weight
      reduction in Caucasians. This study investigated the efficacy and safety of two
      different VLCDs (450 or 800kcal/d) in obese Taiwanese. METHODS: 132 participants
      with BMI > or =30kg/m(2) were randomized to two VLCD groups for body weight
      reduction for 12 weeks. Each group had 66 participants. Anthropometric and
      metabolic parameters were measured. RESULTS: The intention-to-treat analysis
      revealed that the percentage change in body weight over the 12-week treatment
      period was -9.14% in the VLCD-450 group and -8.98% in the VLCD-800 group. A total
      of 27 (40.9%) participants in the VLCD-450 group and 29 (43.9%) participants in
      the VLCD-800 group achieved 10% or more weight loss at the end of treatment. The
      body weight, waist circumference, hip circumference, fat mass, blood pressure,
      triglycerides, and blood glucose were statistically improved from baseline but
      not between the two groups. The improvement rate of nonalcoholic fatty liver
      disease (NAFLD) was 41.5% in the VLCD-450 group and 50.0% in the VLCD-800 group.
      The incidence of adverse events did not differ significantly between the groups
      and no serious adverse events were reported in either group. CONCLUSION: Both the
      VLCD-450 and 800kcal/d can effectively and safely reduce body weight and improve
      NAFLD in 12 weeks in obese Taiwanese participants. However, there is no
      additional benefit in prescribing the more restrictive diet intervention in
      Taiwanese.

PMID- 19592224
TI  - Abnormal collagen deposition in fibromas from patient with juvenile hyaline
      fibromatosis.

PMID- 19592225
TI  - Influenza and bacterial pneumonia.

PMID- 19592226
TI  - Efficacy of antibiotic therapy in polyarthritis: a clue suggesting Whipple's
      disease.

PMID- 19592227
TI  - Characterization of heat-induced interaction of neutral liposome with lipid
      membrane of Streptomyces griseus cell.
AB  - The interaction between the neutral 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylcholine (POPC) liposomes and cell membrane of Streptomyces griseus
      induced by the heat treatment at specific temperature was investigated, focusing
      on the internalization of the neutral POPC liposomes with S. griseus cells. In an
      attempt to clarify the modes of liposome internalization, various kinds of
      inhibitors of endocytotic pathways were used to treat S. griseus cells. The
      efficiency of the heat treatment on liposome-cell membrane interactions was
      finally characterized based on the hydrophobic, electrostatic interactions and
      hydration effect. In fact, the internalization of the neutral liposomes into
      these cells was found to show higher rate and greater amount at higher
      temperatures. The kinetic study showed that the maximum amount of the
      internalized liposomes was, respectively, 469 x 10(5) and 643 x 10(5)
      liposomes/cell at 37 and 41 degrees C. The internalization of the neutral
      liposomes induced by the heat treatment was characterized, implying that the
      endocytosis occurred. The interactions involving the internalization, adsorption,
      and fusion of these liposomes with S. griseus cells were mainly contributed by
      the hydrophobic interaction and the unstable hydrogen bonds caused by the loss of
      water of surface hydration of cell membrane rather than the electrostatic
      interaction under the specific heat condition.

PMID- 19592228
TI  - Re: Proposed ethics and law component of the clinical oncology curriculum.

PMID- 19592229
TI  - Impairments in balance discriminate fallers from non-fallers in COPD.
AB  - BACKGROUND: Preliminary evidence suggests individuals with COPD exhibit deficits
      in balance. Further investigation of balance and risk of falls is warranted in
      these patients. The objective of this study was to determine the clinical
      measures that discriminate fallers from non-fallers among patients with COPD.
      METHODS: A cross-sectional study design was used. Subjects>60 years with COPD
      attended a single assessment session. A one-year incidence of falls was collected
      via self-report questionnaire. Risk of falls and balance were determined using
      the Berg Balance Scale (BBS), Timed Up and Go Test (TUG) and the Activity
      Specific Balance Confidence (ABC) Scale. Exercise tolerance was determined from
      the Six-Minute Walk Test and functional limitation attributable to dyspnea from
      the Medical Research Council (MRC) dyspnea scale. RESULTS: Of the 39 COPD
      subjects (FEV(1)=41.5+/-17.0% predicted; age: 71.1+/-6.8 years) who completed the
      study, 46% (n=18) reported at least one fall in the preceding year. Significant
      differences between fallers and non-fallers were found for the ABC (65.8+/-18.2
      vs. 81.7+/-11.1; p=0.002), TUG (17.0+/-4.9 vs. 14.0+/-3.1s; p=0.024), BBS (45.2+/
      5.4 vs. 48.8+/-5.0; p=0.042), use of supplemental oxygen (72% vs. 24%; p=0.002),
      and MRC dyspnea scale (median 4, range 3 vs. median 3, range 4; p=0.046).
      CONCLUSIONS: Patients with COPD fall frequently. Standard clinical balance
      measures discriminate self-reported fallers from non-fallers. These observations
      draw attention to an important secondary impairment in COPD.

PMID- 19592230
TI  - A disposable and cost efficient microfluidic device for the rapid chip-based
      electrical detection of DNA.
AB  - Requirements for a point-of-care device are an easy and robust read-out and-
      above all--a simple handling. We integrated an established robust electrical read
      out for DNA-chips into a microfluidic device, thereby creating an automated
      analysis system that combines the necessary steps for a chip-based analysis. It
      is based on the electrical detection of biotin-labeled DNA in a gap between two
      microstructured electrodes on the surface of a DNA-chip. The biotin serves as
      binding molecule for streptavidin-conjugated horseradish peroxidase. A following
      enzyme-induced silver deposition bridges the gap by a conductive layer. The
      miniaturized chip gives the possibility to realize a durable system suitable for
      point-of-care applications. To enable an initial automation, all corresponding
      process steps were executed in a miniaturized silicone flow cell. The required
      defined temperatures for the hybridization and the washing steps can be adjusted
      by a heating foil. This paper characterizes the performance of the flow cell
      based system in terms of reaction speed and analysis time, sensitivity as well as
      specificity, and the comparison to a conventional system, without flow cell.
      These first steps of automation and integration will help to realize a laboratory
      independent bioanalytical tool, for the use outside of specialized laboratories
      for fast analysis of different chemical and biological applications.

PMID- 19592231
TI  - Aptamer-Au NPs conjugates-enhanced SPR sensing for the ultrasensitive sandwich
      immunoassay.
AB  - The goal of this work is to explore the amplification effect of aptamer-gold
      nanoparticles (Au NPs) conjugates for ultrasensitive detection of large
      biomolecules by surface plasmon resonance (SPR). A novel sandwich immunoassay is
      designed to demonstrate the amplification effect of aptamer-Au NPs conjugates by
      using human immunoglobulin E (IgE) as model analyte. Human IgE, captured by
      immobilized goat anti-human IgE on SPR gold film, is sensitively detected by SPR
      spectroscopy with a lowest detection limit of 1 ng/ml after anti-human IgE
      aptamer-Au NPs conjugates is used as amplification reagent. Meanwhile, the non
      specific adsorption of aptamer-Au NPs conjugates on goat anti-human IgE is
      confirmed by SPR spectroscopy and then it is minimized by treating aptamer-Au NPs
      conjugates with 6-mercaptohexan-1-ol (MCH). These results confirm that aptamer-Au
      NPs conjugates is a powerful sandwich element and an excellent amplification
      reagent for SPR-based sandwich immunoassay.

PMID- 19592232
TI  - An expanding job description for Blimp-1/PRDM1.
AB  - The master transcriptional regulator Blimp-1/PRDM1 contains an N-terminal PR/SET
      domain and five C2H2 zinc fingers located near its C-terminus that mediate DNA
      binding, nuclear import and recruitment of histone modifying enzymes. These
      activities account for its ability to control cell-fate decisions in the embryo
      and govern tissue homeostasis in multiple cell types in the adult organism. New
      experiments demonstrate an increasing degree of complexity associated with Blimp
      1/PRDM1 target site selection and its associations with epigenetic modifiers. Our
      current understanding of how this single unique species within the family of
      structurally similar PRDM proteins regulates gene expression patterns and governs
      developmental programmes in different cell lineages is discussed.

PMID- 19592233
TI  - Targeting of tamoxifen to enhance antitumour action for the treatment and
      prevention of breast cancer: the 'personalised' approach?
AB  - Tamoxifen is a standard endocrine therapy for the treatment of steroid receptor
      positive breast cancer. Tamoxifen efficacy depends on the formation of clinically
      active metabolites 4-hydroxytamoxifen and endoxifen which have a greater affinity
      to the oestrogen receptor and ability to control cell proliferation as compared
      to the parent drug. The cytochrome P450 2D6 enzyme plays a key role in this
      biotransformation and lack of tamoxifen efficacy has been linked to low activity.
      There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic
      evidence in support of the notion that CYP2D6 genetic variants and phenocopying
      effects through drug interaction by CYP2D6 inhibitors influence plasma
      concentrations of active tamoxifen metabolites and negatively impact tamoxifen
      outcome. These interrelations are particularly critical for patients with non
      functional (poor metaboliser) and severely impaired (intermediate metaboliser)
      CYP2D6 variants, and, moreover, for patients in need of co-medication such as
      serotonin re-uptake inhibitors to control adverse effects such as hot flashes and
      other menopausal symptoms. Therefore, in the future, a personalised approach for
      an optimal tamoxifen benefit should consider a CYP2D6 genotype guided adjuvant
      endocrine treatment strategy and avoid non-adherence as well as strong CYP2D6
      inhibitors such as co-medications.

PMID- 19592234
TI  - Surgical resection of liver metastases from breast cancer.
AB  - The aim of this review is to define the relevance of surgical resection for liver
      metastasis of breast cancer. We report the rationale for hepatic surgery of liver
      metastasis, the survival prognosis factors for these patients, and the influence
      of liver resection on overall survival. The aim of this surgery is not only the
      local control, but also general control of the disease by preventing the
      selection of resistant tumor cell clones. Adjuvant therapies remain necessary for
      general control of the disease. While preoperative detection of small intra
      hepatic lesions remains difficult, MRI and preoperative ultrasound may help.

PMID- 19592235
TI  - Thermophilic biohydrogen production by an anaerobic heat treated-hot spring
      culture.
AB  - Batch experiments were conducted to investigate the thermophilic biohydrogen
      production using an enrichment culture from a Turkish hot spring. Following the
      enrichment, the culture was heat treated at 100 degrees C for 10 min to select
      for spore-forming bacteria. H(2) production was accompanied by production of
      acetate, butyrate, lactate and ethanol. H(2) production was associated by acetate
      butyrate type fermentation while accumulation of lactate and ethanol negatively
      affected the H(2) yield. H(2) production was highest in the temperature range
      from 49.6 to 54.8 degrees C and optimum values for initial pH and concentrations
      of iron, yeast extract and glucose were 6.5, 40 mg/l, 4-13.5 g/l, respectively.
      PCR-DGGE profiling showed that the heat treated culture consisted of species
      closely affiliated to genus Thermoanaerobacterium.

PMID- 19592236
TI  - Anaerobic digestion of glycerol derived from biodiesel manufacturing.
AB  - The anaerobic digestion of glycerol derived from biodiesel manufacturing, in
      which COD was found to be 1010 g/kg, was studied in batch laboratory-scale
      reactors at mesophilic temperature using granular and non-granular sludge. Due to
      the high KOH concentration of this by-product, H(3)PO(4) was added to recover
      this alkaline catalyst as agricultural fertilizer (potassium phosphates).
      Although it would not be economically viable, a volume of glycerol was distilled
      and utilised as reference substrate. The anaerobic revalorisation of glycerol
      using granular sludge achieved a biodegradability of around 100%, while the
      methane yield coefficient was 0.306 m(3) CH(4)/kg acidified glycerol. Anaerobic
      digestion could be a good option for revalorising this available, impure and low
      priced by-product derived from the surplus of biodiesel companies. The organic
      loading rate studied was 0.21-0.38 g COD/g VSS d, although an inhibition
      phenomenon was observed at the highest load.

PMID- 19592237
TI  - Effect of culture medium composition on Trichoderma reesei's morphology and
      cellulase production.
AB  - The objective of this study was to determine how fungal morphology influences the
      volumetric cellulase productivity of Trichoderma reesei cultured in four media
      with lactose and lactobionic acid as fed-batch in a 7 L stirred tank bioreactor.
      The use of a cellulose-yeast extract culture medium yielded the highest enzyme
      production with a volumetric enzyme activity of 69.8 U L(-1) h(-1), and a maximum
      fungal biomass of 14.7 g L(-1). These findings were associated with the following
      morphological characteristics of the fungus: total mycelia was 98% of total mean
      projected area, mean hyphae length of 10 mm, mean hyphae volume of 45.1 mm(3),
      mean hyphae diameter of 7.9 microm, number of branches 9, and number of tips per
      hypha 29. A positive correlation was found between the total mycelia, the number
      of tips and the volumetric enzyme productivity, indicating the weight of these
      variables on the enzyme productivity.

PMID- 19592238
TI  - Sensitivity of Aedes aegypti adults (Diptera: Culicidae) to the vapors of
      Eucalyptus essential oils.
AB  - Vapors of essential oils extracted from various species of Eucalyptus (E. gunnii,
      E. tereticornis, E. grandis, E. camaldulensis, E. dunnii, E. cinerea, E. saligna,
      E. sideroxylon, E. globulus ssp. globulus, E. globulus ssp. maidenii, E.
      viminalis and the hybrids E. grandisxE. tereticornis and E. grandisxE.
      camaldulensis) and their major components were found to be toxic to Aedes aegypti
      adults, the yellow fever mosquito. An aliquot of each oil was placed in a
      cylindrical test chamber and the number of knocked-down mosquitoes was recorded
      as function of time. Knockdown time 50% was then calculated. Results showed that
      E. viminalis had the fastest knockdown time at of 4.2 min, on the same order as
      dichlorvos, a standard knockdown agent. A correlation was observed between the
      content of 1,8-cineole in the Eucalyptus essential oils and the corresponding
      toxic effect. The correlation between KT(50) values and calculated vapor
      pressures of the essential oil components showed that the fumigant activity of
      simple organic compounds in insects is correlated with their volatility.

PMID- 19592239
TI  - A comparison of used cooking oils: a very heterogeneous feedstock for biodiesel.
AB  - Used cooking or frying oils are of increasing interest as inexpensive feedstock
      for biodiesel production. In this work, used frying oils obtained from 16 local
      restaurants were investigated regarding their fatty acid profile vs. the fatty
      acid profile of the oil or fat prior to use. The fatty acid profiles were
      analyzed by gas chromatography and proton nuclear magnetic resonance
      spectroscopy. Besides the fatty acid profile, the acid value and dynamic
      viscosity of the samples were determined. Dynamic viscosity was determined
      because of non-Newtonian behavior of some samples. The results indicate that oils
      and fats experience various degrees of increase in saturation during
      cooking/frying use, with the magnitude of these changes varying from sample to
      sample, i.e., a high degree of randomness of composition is found in used frying
      oil samples. Properties of the samples that were investigated were acid value and
      viscosity which consistently increased with use, also in a random fashion.
      Multiple independent samples obtained from the same restaurants indicate that
      there is little consistency of used cooking oil obtained from the same source.
      These results are discussed with regards to the potential fuel properties of
      biodiesel derived from these used frying oils.

PMID- 19592240
TI  - Factors affecting ferulic acid release from Brewer's spent grain by Fusarium
      oxysporum enzymatic system.
AB  - In this study, the factors affecting ferulic acid (FA) release from Brewer's
      spent grain (BSG), by the crude enzyme extract of Fusarium oxysporum were
      investigated. In order to evaluate the importance of the multienzyme preparation
      on FA release, the synergistic action of feruloyl esterase (FAE, FoFaeC-12213)
      and xylanase (Trichoderma longibrachiatum M3) monoenzymes was studied. More than
      double amount of FA release (1 mg g(-1) dry BSG) was observed during hydrolytic
      reactions by the crude enzyme extract compared to hydrolysis by the monoenzymes
      (0.37 mg g(-1) dry BSG). The protease content of the crude extract and the
      inhibitory effect of FA as an end-product were also evaluated concerning their
      effect on FA release. The protease treatment prior to hydrolysis by monoenzymes
      enhanced FA release about 100%, while, for the first time in literature, FA in
      solution found to have a significant inhibitory effect on FAE activity and on
      total FA release.

PMID- 19592241
TI  - Characteristics and kinetics of cattle litter pyrolysis in a tubing reactor.
AB  - The kinetic parameters for the pyrolysis of cattle litter were evaluated by
      thermogravimetric analysis (TGA). The cattle litter was pyrolyzed in a tubing
      reactor at 340, 360 and 380 degrees C with various retention times from 4 to 20
      min. The influence of the pyrolysis conditions on the product yields was also
      examined. The maximum yields of gas and liquid products, 16.1 and 17.2 wt%,
      respectively, were obtained after pyrolysis at 380 degrees C for 20 min. The gas
      products were mainly C(1)-C(4) hydrocarbons. The experimental results of the
      product distribution were well fitted with the lumped kinetic model. The reaction
      pathway was investigated based on the calculated kinetic constants.

PMID- 19592242
TI  - Pyrazole acids as niacin receptor agonists for the treatment of dyslipidemia.
AB  - Niacin is an effective drug for raising HDL cholesterol and reducing coronary
      risks, but patients show low compliance with treatment due to severe facial
      flushing upon taking the drug. A series of bicyclic pyrazole carboxylic acids
      were synthesized and tested for their ability to activate the niacin receptor.
      One analog, 23, showed improved potency and lacked flushing at doses that
      effectively altered the lipid profile of rats.

PMID- 19592243
TI  - Novel, achiral aminoheterocycles as selective monoamine reuptake inhibitors.
AB  - A variety of novel aminoheterocycle scaffolds as selective monoamine reuptake
      inhibitors have been prepared and one of these scaffolds is achiral. The main
      elements responsible for hERG channel, CYP2D6 and CYP3A4 inhibition were
      identified.

PMID- 19592245
TI  - Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro
      reporter gene assay.
AB  - The effect of 32 flavonoids on androgen (AR) and glucocorticoid receptors (GR)
      was investigated using an MDA-kb2 human breast cancer cell line to predict
      potential AR and GR activities. Among them, 5-hydroxyflavone (7) had the highest
      AR antagonistic activity with an IC(50) value of 0.3 microM, whereas 6
      methoxyflavone (11) had the highest induced luciferase activity with an EC(150)
      value of 0.7 microM. Genistein (2) and daizein (1) showed a sufficient increase
      of luciferase activities as their concentrations increased with EC(150) values of
      4.4 and 10.1 microM, respectively. These findings provide evidence of a
      fundamental property of their structure-activity relationship with AR and/or GR.

PMID- 19592244
TI  - 7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor
      antagonists.
AB  - High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a
      novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a
      highly selective compound with good functional potency for inhibition of human
      eosinophil shape change in whole blood and oral bioavailability in the rat.

PMID- 19592246
TI  - Novel derivatives of ISO-1 as potent inhibitors of MIF biological function.
AB  - A series of novel 1,2,4-oxadiazole, phthalimide, amide and other derivatives of
      ISO-1 were synthesized and probed for inhibition of macrophage migration
      inhibitory factor (MIF) activity. Several compounds inhibited MIF enzymatic
      activity at levels better than ISO-1. Of note, compounds 7, 22, 23, 24, 25 and 27
      inhibited the spontaneous secretion/release/recognition of MIF from freshly
      isolated human peripheral blood mononuclear cells and, more importantly,
      inhibited the MIF-induced production of interleukin-6 (IL-6) and/or interleukin
      1beta (IL-1beta) significantly better than ISO-1.

PMID- 19592247
TI  - Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists.
AB  - Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative,
      the NFkappaB agonist activity was optimised in an iterative process from pIC(50)
      7.5 (for 7), to pIC(50) 10.1 (for 38E1). An explanation for the SAR observed
      based is presented along with a proposed docking of 38E1 into the active site of
      the glucocorticoid receptor.

PMID- 19592248
TI  - Protein phosphatase 1 regulates exit from the spindle checkpoint in budding
      yeast.
AB  - Accurate chromosome segregation depends on sister kinetochores coming under
      tension when they make bioriented attachments to microtubules from opposite
      poles. The spindle checkpoint halts the cell cycle in response to defects in
      generating proper attachments or tension on kinetochores, although the precise
      signal that triggers the checkpoint is unclear because tension and attachment are
      coupled. The target of the checkpoint is the Cdc20 protein, which initiates the
      anaphase-promoting complex (APC)-dependent degradation of the anaphase inhibitor
      Pds1/securin. Although the molecular details of spindle checkpoint activation are
      still being elucidated, phosphorylation by at least four kinases is a crucial
      requirement. However, less is known about the mechanisms that silence the
      checkpoint after kinetochores biorient. Here, we show that the catalytic subunit
      of the budding yeast protein phosphatase 1 (PP1) homolog, Glc7, regulates exit
      from the checkpoint. Glc7 overexpression prevents spindle checkpoint activation
      in response to both tension and attachment defects. Although glc7 mutant cells
      are able to efficiently release from a non-checkpoint-mediated metaphase arrest,
      they are uniquely sensitive to transient spindle checkpoint activation as a
      result of a failure in spindle checkpoint exit. We therefore propose that PP1
      activity silences the checkpoint by reversing key phosphorylation events.

PMID- 19592249
TI  - A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism.
AB  - The spindle checkpoint is a surveillance system acting in mitosis to delay
      anaphase onset until all chromosomes are properly attached to the mitotic
      spindle. When the checkpoint is activated, the Mad2 and Mad3 proteins directly
      bind and inhibit Cdc20, which is an essential activator of an E3 ubiquitin ligase
      known as the anaphase-promoting complex (APC). When the checkpoint is satisfied,
      Cdc20-APC is activated and polyubiquitinates securin and cyclin, leading to the
      dissolution of sister chromatid cohesion and mitotic progression. Several protein
      kinases play critical roles in spindle checkpoint signaling, but the mechanism
      (or mechanisms) by which they inhibit mitotic progression remains unclear.
      Furthermore, it is not known whether their activity needs to be reversed by
      protein phosphatases before anaphase onset can occur. Here we employ fission
      yeast to show that Aurora (Ark1) kinase activity is directly required to maintain
      spindle checkpoint arrest, even in the presence of many unattached kinetochores.
      Upon Ark1 inhibition, checkpoint complexes are disassembled and cyclin B is
      rapidly degraded. Importantly, checkpoint silencing and cyclin B degradation
      require the kinetochore-localized isoform of protein phosphatase 1 (PP1(Dis2)).
      We propose that PP1(Dis2)-mediated dephosphorylation of checkpoint components
      forms a novel spindle checkpoint silencing mechanism.

PMID- 19592250
TI  - Blue and yellow signal cleaning behavior in coral reef fishes.
AB  - Marine cleaning symbioses are classic examples of mutualism: cleaners remove and
      consume ectoparasites from "client" fish, while clients benefit from a reduction
      in ectoparasites. However, how clients recognize cleaners and decide not to eat
      them is unclear. Color and body pattern are thought to be important in signaling
      cleaning services to coral reef fish; in this study, we tested the long-held
      belief that cleaner fish display a blue "guild" coloration. Via color analytical
      techniques and phylogenetic comparisons, we show that cleaner fish are more
      likely to display a blue coloration, in addition to a yellow coloration, compared
      to noncleaner fish. Via theoretical vision models, we show that, from the
      perspective of potential signal receivers, blue is the most spectrally
      contrasting color against coral reef backgrounds, whereas yellow is most
      contrasting against blue water backgrounds or against black lateral stripes.
      Finally, behavioral experiments confirm that blue within the cleaner fish pattern
      attracts more client reef fish to cleaning stations. Cleaner fish have evolved
      some of the most conspicuous combinations of colors and patterns in the marine
      environment, and this is likely to underpin the success of the cleaner-client
      relationship on the reef.

PMID- 19592251
TI  - ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory
      signaling pathways.
AB  - BACKGROUND: The inability to coordinate the signaling pathways that lead to
      proper cytokine responses characterizes the pathogenesis of inflammatory diseases
      such as Crohn's disease. The Crohn's disease susceptibility protein, NOD2, helps
      coordinate cytokine responses upon intracellular exposure to bacteria, and this
      signal coordination by NOD2 is accomplished, in part, through K63-linked
      polyubiquitin chains that create binding surfaces for the scaffolding of
      signaling complexes. RESULTS: In this work, we show that the NOD2 signaling
      partner, RIP2, is directly K63-polyubiquitinated by ITCH, an E3 ubiquitin ligase
      that when lost genetically causes widespread inflammatory disease at mucosal
      surfaces. We show that ITCH is responsible for RIP2 polyubiquitination in
      response to infection with listeria monocytogenes. We also show that NOD2 can
      bind polyubiquitinated RIP2 and that whereas ITCH E3 ligase activity is required
      for optimal NOD2:RIP2-induced p38 and JNK activation, ITCH inhibits NOD2:RIP2
      induced nuclear factor kappa B (NFkappaB) activation. This effect can be seen
      independently at the whole-genome level by microarray analysis of muramyl
      dipeptide (MDP)-treated Itch(-/-) primary macrophages. CONCLUSIONS: These
      findings suggest that ITCH helps regulate NOD2-dependent signal transduction
      pathways and, as such, may be involved in the pathogenesis of NOD2-mediated
      inflammatory disease.

PMID- 19592252
TI  - Cellular dissection of circadian peptide signals with genetically encoded
      membrane-tethered ligands.
AB  - BACKGROUND: Neuropeptides regulate many biological processes. Elucidation of
      neuropeptide function requires identifying the cells that respond to neuropeptide
      signals and determining the molecular, cellular, physiological, and behavioral
      consequences of activation of their cognate G protein-coupled receptors (GPCRs)
      in those cells. As a novel tool for addressing such issues, we have developed
      genetically encoded neuropeptides covalently tethered to a
      glycosylphosphatidylinositol (GPI) glycolipid anchor on the plasma membrane ("t
      peptides"). RESULTS: t-peptides cell-autonomously induce activation of their
      cognate GPCRs in cells that express both the t-peptide and its receptor. In the
      neural circuit controlling circadian rest-activity rhythms in Drosophila
      melanogaster, rhythmic secretion of the neuropeptide pigment-dispersing factor
      (PDF) and activation of its GPCR (PDFR) are important for intercellular
      communication of phase information and coordination of clock neuron oscillation.
      Broad expression of t-PDF in the circadian control circuit overcomes
      arrhythmicity induced by pdf(01) null mutation, most likely as a result of
      activation of PDFR in PDFR-expressing clock neurons that do not themselves
      secrete PDF. More restricted expression of t-PDF suggests that activation of PDFR
      accelerates cellular timekeeping in some clock neurons while decelerating others.
      CONCLUSIONS: The activation of PDFR in pdf(01) null mutant flies--which lack PDF
      mediated intercellular transfer of phase information--induces strong rhythmicity
      in constant darkness, thus establishing a distinct role for PDF signaling in the
      circadian control circuit independent of the intercellular communication of
      temporal phase information. The t-peptide technology should provide a useful tool
      for cellular dissection of bioactive peptide signaling in a variety of organisms
      and physiological contexts.

PMID- 19592253
TI  - The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal
      transduction during development.
AB  - The Hedgehog (Hh) signaling pathway regulates development in animals ranging from
      flies to humans. Although its framework is conserved, differences in pathway
      components have been reported. A kinesin-like protein, Costal2 (Cos2), plays a
      central role in the Hh pathway in flies. Knockdown of a zebrafish homolog of
      Cos2, Kif7, results in ectopic Hh signaling, suggesting that Kif7 acts primarily
      as a negative regulator of Hh signal transduction. However, in vitro analysis of
      the function of mammalian Kif7 and the closely related Kif27 has led to the
      conclusion that neither protein has a role in Hh signaling. Using Kif7 knockout
      mice, we demonstrate that mouse Kif7, like its zebrafish and Drosophila homologs,
      plays a role in transducing the Hh signal. We show that Kif7 accumulates at the
      distal tip of the primary cilia in a Hh-dependent manner. We also demonstrate a
      requirement for Kif7 in the efficient localization of Gli3 to cilia in response
      to Hh and for the processing of Gli3 to its repressor form. These results suggest
      a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and
      preventing Gli3 cleavage into a repressor form in the presence of Hh.

PMID- 19592254
TI  - The role and interaction of visual and auditory afferents in postural stability.
AB  - BACKGROUND: Maintaining balance requires the integration of vestibular,
      proprioceptive and visual information and the translation of this input into
      appropriate motor responses. Although the role of the visual system has been
      widely investigated, there are no studies addressing the influence of non
      specific distracting auditory inputs on postural stability. OBJECTIVE: To analyze
      the role of the visual and auditory systems in the maintenance of postural
      stability and to assess potential interaction between the two sensory systems.
      METHODS: Twenty-three healthy subjects were examined by computerized dynamic
      posturography. Stability index scores were calculated under each of six
      conditions: three visual conditions (sway feedback, eyes open without feedback,
      eyes closed) were combined with two auditory conditions (exposure or no exposure
      to non-specific auditory input). Analysis of variance (ANOVA) was used to test
      for differences among groups in the six test conditions. RESULTS: Postural
      stability was much poorer in the eyes-closed (overall stability index (OSI):
      6.8+/-2.1 degrees) than in the eyes-open condition (OSI: 2.2+/-1.2 degrees).
      Balance control significantly improved with visual feedback (OSI: 1.2+/-0.5
      degrees). Exposure to non-specific auditory input (music through headphones) did
      not have a significant influence (OSI: 6.4+/-2.3 degrees /2.0+/-0.9 degrees
      /1.1+/-0.5 degrees). CONCLUSIONS: Postural stability depended not only on whether
      the subjects were tested with their eyes open or closed but also on the presence
      or absence of visual feedback. Non-specific auditory information did not
      influence postural control. Since postural stability is regulated by multiple
      senses such as the vestibular system and proprioception, auditory stimuli may
      play an increasing role if one of the systems involved is impaired.

PMID- 19592255
TI  - Hyperhomocysteinemia and MTHFR C677T homozygosity in a vegetarian male with
      sinovenous thrombosis of the brain.

PMID- 19592256
TI  - Polymer supported synthesis of aminooxyalkylated oligonucleotides, and some
      applications in the fabrication of microarrays.
AB  - A new protocol has been described for solid phase preparation of 3'- and 5'
      aminooxylalkylated oligonucleotides using commercially available reagents. This
      involves attachment of linker 4 either with an LCAA-CPG support via
      succinoylation followed by synthesis (3'-aminooxyalkylated oligomers) or
      formation of its phosphoramidite 6 followed by coupling with desired oligomer
      (for generating 5'-aminooxyalkylated oligomers). Both the routes produced
      modified oligonucleotides in sufficiently high yields and purity (on HPLC) via
      conventional oligonucleotide synthesis on an automated synthesizer and
      deprotection step using aqueous ammonia (16 h, 60 degrees C). Aminooxyalkylated
      oligonucleotides were used to construct microarrays on glass surface (biochips).
      The performance of the biochips was evaluated by immobilizing modified
      oligonucleotides on epoxylated glass microslides under different sets of
      conditions with respect to pH, temperature and time. Further, the constructed
      microarrays were successfully used for detection of nucleotide mismatches and
      bacterial typhoid.

PMID- 19592257
TI  - Systematic syntheses of influenza neuraminidase inhibitors: a series of
      carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic
      acid moieties.
AB  - In order to develop novel influenza sialidase inhibitors, we constructed a
      library of glycoclusters composed of twelve types of sialylated dendrimers with
      thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These
      sialodendrimers were synthesized by condensation reaction between a thiosialoside
      modified on the aglycon terminal end by a thioacetyl group and twelve types of
      carbosilane dendrimers having brominated terminal ends under deacetylation
      conditions, and temporal re-protection was performed for purification. Removal of
      all protection of the glycodendrimers was accomplished by transesterification and
      subsequent saponification to provide corresponding water-soluble glycodendrimers
      in good yields. For investigation of the structure-activity relationship,
      dendrimer scaffolds having differences in number of the sugar moieties, such as 3
      , 4-, 6- and 12-functionalized dendrimers, and in linkage patterns, such as
      normal aliphatic linkage, ether- and amide-linkages. Biological evaluations of
      these glycodendrimers showed that all of the ether- and amide-elongated compounds
      had inhibitory potencies for the influenza sialidases in the mM range, while
      compounds having normal aliphatic linkage did not have any activities except for
      a 12-functionalized compound.

PMID- 19592258
TI  - Parallel synthesis of potent dopaminergic N-phenyltriazole carboxamides applying
      a novel click chemistry based phenol linker.
AB  - Taking advantage of our click chemistry based methodology to construct novel SPOS
      (solid phase organic synthesis) resins, the triazolylmethyl linked catechol 6a
      was discovered, which is readily available via copper(I)-catalyzed azide-alkyne
      cycloaddition (CuAAC) of azidomethyl substituted polystyrene with O
      propargylcatechol and can be applied for the parallel synthesis of N
      phenyltriazole carboxamides. As a proof-of-concept, a 'catch-and-release'
      strategy could be successfully applied for a parallel synthesis of dopaminergic
      phenyltriazoles of type 2. A focused model library of 20 test compounds revealing
      three points of diversity was generated by a three-step SPOS approach. Product
      purification was performed employing a solid-supported carboxylic acid anhydride
      as a scavenger. GPCR-ligand binding screening revealed dopamine D3 receptor
      ligands with K(i) values in the single digit nanomolar range.

PMID- 19592259
TI  - Design and synthesis of acetamido tri- and tetra-hydroxyazepanes: potent and
      selective beta-N-acetylhexosaminidase inhibitors.
AB  - A series of seven-membered iminosugars bearing an acetamido group beta- or gamma-
      to the endocyclic nitrogen have been synthesized via simple transformations of
      previously described polysubstituted azepanes. These tetra- and trihydroxylated
      acetamido azepanes are ring homologues of 2-acetamido-1,2-dideoxy
      glyconojirimycins and 2-acetamido-1-N-iminosugars respectively. Screening of
      these azepanes towards a range of commercially available glycosidases
      demonstrated their potential as selective and potent hexosaminidase inhibitors
      with K(i)'s in the submicromolar range. A correlation between the relative
      configuration of the azepanes and their ability to inactivate hexosaminidases was
      also observed for the first time for this class of compounds with one notable
      exception for the most potent compound.

PMID- 19592261
TI  - Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and
      evaluation of risk.
AB  - INTRODUCTION: The purpose of this study was to identify factors that influence
      bisphosphonate-related osteonecrosis of the jaws (BRONJ). PATIENTS AND METHODS:
      Patients undergoing treatment for BRONJ (n=34) were evaluated. Sex, age,
      underlying diagnosis, type of bisphosphonate (BP), duration and route of
      administration, location of osteonecrosis, clinical symptoms, Actinomyces
      colonisation, treatment and outcome were recorded. Symptom onset was analysed
      with respect to BP potency and cumulative dose. RESULTS: Underlying diagnoses
      indicating BP-treatment included multiple myeloma, breast carcinoma, prostate
      carcinoma and osteoporosis. In 31 patients, BRONJ was preceded by tooth
      extraction, root apicotomy, ill-fitting dentures, cystenucleation, implant
      insertion or trauma; in 3 patients, the precipitating event was not identified.
      Actinomyces colonisation was observed in 18 patients (53%). The occurrence of
      BRONJ was not directly related to BP dose or potency. More women with multiple
      myeloma had BRONJ than did males. BRONJ was observed in osteoporotic patients
      treated with both corticosteroids and BPs. CONCLUSIONS: BRONJ was not primarily
      associated with BP potency or dose. Factors that increased the risk of
      osteonecrosis were female sex, oral surgery and corticosteroids plus intravenous
      or oral BP administration. BP deposition in the jaw bones might enhance BRONJ by
      promoting bacterial colonisation; however, this hypothesis requires more study.

PMID- 19592260
TI  - Synthetic strategies toward carbocyclic purine-pyrimidine hybrid nucleosides.
AB  - The blending of key structural features from the purine and pyrimidine nucleobase
      scaffolds gives rise to a new class of hybrid nucleosides. The purine-pyrimidine
      hybrid nucleosides can be viewed as either N-3 ribosylated purines or 5,6
      disubstituted pyrimidines, thus recognition by both purine- and pyrimidine
      metabolizing enzymes is possible. Given the increasing reports of the development
      of resistance in many enzymatic systems, a drug that could be recognized by more
      than one enzyme could prove highly advantageous in overcoming resistance
      mechanisms related to binding site mutations. In that regard, the design,
      synthesis and results of preliminary biological activity for a series of
      carbocyclic uracil derivatives with either a fused imidazole or thiazole ring are
      presented herein.

PMID- 19592263
TI  - Impending rupture of the left atrium after impaction of left atrial ablation
      catheter.

PMID- 19592264
TI  - Risk factors of atrial fibrillation following off-pump coronary artery bypass
      graft surgery: predictive value of C-reactive protein and transfusion
      requirement.
AB  - OBJECTIVES: Considering the role of inflammatory reaction on the pathogenesis of
      atrial fibrillation (AF), the aim of this study is to investigate perioperative
      risk factors of AF, as well as to validate the predictive value of high-sensitive
      C-reactive protein (hsCRP), and transfusion requirement following off-pump
      coronary bypass surgery (OPCAB) in a prospective and observational trial.
      METHODS: In this cohort, 315 consecutive patients with normal sinus rhythm (NSR)
      undergoing elective isolated OPCAB are prospectively studied. The patients were
      classified as either NSR or AF group according to their postoperative rhythm,
      which was continuously monitored for the first 6 postoperative days. RESULTS: AF
      developed in 66 patients (19%). Univariate analysis demonstrated old age, pre
      existing chronic renal failure, low left ventricle ejection fraction (LVEF <30%),
      highest hsCRP before the onset of AF, vasopressor and inotropic therapy, packed
      red blood cells (pRBCs) transfusion and amount of chest tube drainage as
      predictors of postoperative AF. In a stepwise multivariate analysis of these risk
      factors, low LVEF (odds ratio: 2.88; 95% confidence interval: 1.07-7.75;
      p=0.037), highest hsCRP before the onset of AF (odds ratio: 1.06; 95% confidence
      interval: 1.01-1.11; p=0.018), vasopressor therapy (odds ratio: 1.93; 95%
      confidence interval: 1.04-3.57; p=0.038) and pRBC transfusion (odds ratio: 5.32;
      95% confidence interval: 2.80-10.11; p<0.001) remained as independent predictors
      of postoperative AF. CONCLUSIONS: Prophylactic strategies aimed at AF reduction
      may also be considered especially in patients with increased transfusion
      requirement, which showed highest predictive value for postoperative AF.

PMID- 19592265
TI  - Role of endovascular repair in the management of late pseudo-aneurysms following
      open surgery for aortic coarctation.
AB  - BACKGROUND: Coarctation of the aorta accounts for almost 5% of all congenital
      cardiac malformations, and it is usually treated by open surgical procedures.
      Despite the excellent primary results, many patients may develop anastomotic
      pseudo-aneurysms, associated with considerable morbidity and mortality rates. We
      investigated the role of endovascular repair as an alternative to open re-do
      surgery on the descending aorta. METHODS: We retrospectively collected data of 11
      consecutive patients who presented with pseudo-aneurysms of the descending aorta
      following previous surgical repair of congenital aortic coarctation. Nine
      patients developed a pseudo-aneurysm after patch aortoplasty, while an
      interposition graft repair was performed in two cases. Seven patients underwent
      an endovascular repair (26.9 years after the previous open surgery). Four
      patients with a pseudo-aneurysm after coarctation repair associated with arch
      hypoplasia underwent conventional open re-operation. RESULTS: No complications or
      death were observed in the conventional surgical group. Technical success was
      obtained in all patients who received a stent-graft procedure. More than one
      stent graft was necessary only in one case. A left carotid-left subclavian artery
      bypass was performed in three patients. Type II endoleak was detected by
      angiography in one patient who had previously undergone subclavian re
      vascularisation. The median follow-up (FU) was 44.5 months and was 100% complete.
      Neither re-operations nor complications or deaths occurred during FU.
      CONCLUSIONS: Endovascular repair of pseudo-aneurysms following open surgery for
      aortic coarctation is feasible and safe. However, more patients and longer follow
      up are necessary to assess the efficacy of this promising less-invasive
      alternative to open re-do surgery.

PMID- 19592266
TI  - Prophylactic treatment with levosimendan: a retrospective matched-control study
      of patients with reduced left ventricular function.
AB  - OBJECTIVE: Levosimendan is a calcium-sensitising inotropic agent and a
      vasodilator used in the treatment of heart failure. Post-cardiotomy cardiac
      failure is more common in patients with a low preoperative left ventricular
      ejection fraction (LVEF). We aim at investigating how prophylactic treatment with
      levosimendan before weaning from cardiopulmonary bypass (CPB) affects
      postoperative haemodynamics and outcome in patients with low preoperative LVEF.
      METHODS: Patients with a preoperative LVEF < or =30% treated with levosimendan
      before weaning from CPB were included in the study. Each patient was matched to a
      control patient with respect to the following criteria: surgical procedure,
      EuroSCORE, age, gender and the use of intra-aortic balloon pump. We investigated
      postoperative haemodynamics in the intensive care unit (ICU) at time points: 1,
      arrival; 2, approximately 7h after arrival; and 3, the first postoperative
      morning. In addition, mortality was evaluated. RESULTS: Thirty patients treated
      with levosimendan and 30 matched controls were enrolled in the study. No
      statistically significant differences in cardiac index (CI) (l min(-1)m(-2)),
      stroke volume index (SVI) (mlm(-2)), mixed venous O(2)-saturation (SvO(2)) (%) or
      heart rate (HR) (beats per minute) between the two groups measured at the three
      time points 1-3 were registered. Mean arterial blood pressure (MAP) (mmHg) was
      lower in the levosimendan group both at time points 2 (68, range: 65-71 vs 75,
      range: 72-78; p=0.009) and 3 (72, range: 69-74 vs 78, range: 74-82; p=0.01),
      despite a higher dose of norepinephrine in the treatment group (p=0.021). A
      significantly higher number of control patients were treated with classic
      adrenergic inotropes both in the operating room (p=0.013) and in the ICU
      (p<0.001). Thirty days mortality was the same in both groups (7%). CONCLUSIONS:
      Prophylactic infusion of levosimendan initiated before weaning from CPB did not
      lead to superior haemodynamic parameters (CI, SVI, SvO(2)) compared to controls.
      Levosimendan reduced MAP and increased the need for norepinephrine
      postoperatively.

PMID- 19592267
TI  - Sleeve lobectomy for patients with non-small-cell lung cancer: a simplified
      approach.
AB  - OBJECTIVE: Pulmonary parenchyma-saving procedures, indicated for central tumours,
      seem to have better results than pneumonectomy, an alternative procedure. The
      purpose of this study is to report our experience at our institution with sleeve
      lobectomy with regard to surgical technique and outcome. METHODS: We
      retrospectively reviewed the records of 45 patients who underwent sleeve
      lobectomy for non-small-cell lung cancer, with a curative intent, during the
      period of January 2004 and January 2008. Four of these patients underwent
      bronchovascular reconstructive procedures. A minor modification of the running
      suture technique used for bronchoplasties is described here. RESULTS: The study
      identified 40 men and five women with a median age of 64 years (range: 24-80
      years). All 45 patients underwent oncological resections with negative results
      for malignancy bronchial resection margins. Neither bronchial nor vascular
      complications occurred. Complications were observed in 15% of our patients and
      included prolonged air leak in three, atelectasis needing daily bronchoscopy in
      three and respiratory failure due to pneumonia in one patient, who eventually
      died, accounting for a mortality rate of 2%. The follow-up period ranged from 1
      to 52 months, with a median of 26 months, and it was complete for 43 (96%) of the
      patients. The overall 4-year survival was 57%. CONCLUSIONS: Sleeve lobectomy for
      lung cancer, although technically demanding, is associated with low morbidity and
      mortality and satisfactory immediate and long-term results. With increasing
      experience, more lung-sparing procedures should be performed in selected
      patients.

PMID- 19592268
TI  - Increased number of cerebral emboli during percutaneous endocardial pulmonary
      vein isolation versus a thoracoscopic epicardial approach.
AB  - OBJECTIVE: Pulmonary vein isolation (PVI) using ablation energy appears an
      effective treatment for atrial fibrillation (AF) with a success rate of
      approximately 80%. However, post-procedural neurological complications still
      occur in 0.5-10% of all patients undergoing PVI, presumably due to embolism.
      Therefore, we investigated the occurrence of cerebral micro-embolic signals (MES)
      as a surrogate marker for the risk of neurological impairment of two different
      PVI methods: (1) percutaneous endocardial radio-frequency (RF) ablation and (2)
      thoracoscopic epicardial ablation using RF energy. METHODS: Ten patients (eight
      persistent AF and two paroxysmal AF) underwent a minimally invasive thoracoscopic
      epicardial (EPI) RF ablation and 10 patients (one persistent AF and nine
      paroxysmal AF) underwent a percutaneous endocardial (ENDO) isolation.
      Transcranial Doppler (TCD) was used to detect an MES in the middle cerebral
      arteries. RESULTS: An average of 5 (+/-6) MES were detected during epicardial PVI
      procedure versus 3908 (+/-2816) MES during percutaneous endocardial PVI
      procedure. During the ablation application period, respectively, 1 (+/-1) and
      2566 (+/-2296) cerebral MES were detected. CONCLUSIONS: Cerebral micro-emboli
      during epicardial ablation are almost absent when compared to the thousands of
      emboli measured during percutaneous endocardial ablation.

PMID- 19592269
TI  - New aspects in photodynamic therapy of actinic keratoses.
AB  - Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) or its methyl
      ester (MAL) is a very effective method to treat actinic keratosis (AK). New
      developments will contribute to optimization of this treatment modality. This
      will partly be based on a better understanding of the nature of AKs. Since pain
      during treatment is a frequent side effect of PDT, new methods of alleviating
      pain are of high interest, especially when large areas are treated. A better
      understanding of the underlying mechanism of specific protoporphyrin IX (PPIX)
      accumulation can lead to further increase the response rates. New formulations
      might contribute to a wider acceptance of the treatment, for example a self
      adhesive patch containing 5-ALA, promises easy handling, while maintaining high
      efficacy. New concepts in illumination, such as ambulatory PDT or daylight
      illumination might contribute to the further acceptance of this method.

PMID- 19592270
TI  - Seizure frequency in children with epilepsy: factors influencing accuracy and
      parental awareness.
AB  - RATIONALE: The objective of this study was to ascertain the accuracy of clinical
      reports to determine the seizure frequency in children diagnosed with epilepsy.
      METHODS: We reviewed the clinical record of 78 children (January-May of 2006)
      admitted to the EEG-video monitoring with epilepsy diagnosis. Clinical reports of
      parents and the files of EEG-video monitoring were reviewed to determine parents'
      awareness for seizures. RESULTS: During video-EEG monitoring, 1244 were recorded
      on 78 children. Seizures were confirmed in 1095 of which 472 were correctly
      reported (38%) by parents whereas 623 remained under-reported (50%). Parents'
      report thus had a sensitivity of 43%, positive predictive value of 76% to
      identify seizures. Based on the EEG-video monitoring, seizures were reported
      accurately in 22 (28%) and under-reported in 38 (49%) children. In the under
      reported group, none of the seizures were recognized in 10 (13%), only a portion
      identified in 28 children. The parents' report describing seizure frequency has
      limited value for young children (p=0.01) and children with absence seizures
      (p=0.03). However, clinical reports were accurate for the children with
      developmental delay (p<0.06) or not being on any anticonvulsant drug (AED)
      therapy (p=0.02). CONCLUSION: Our results indicate that a significant number of
      seizures remain under-reported by parents of children with epilepsy. The current
      study underscores that the seizure frequency should be interpreted with caution
      for young children and children with absence seizures. Video-EEG recording has a
      complimentary role to the clinical observation for the accurate assessment of
      seizure frequency in children.

PMID- 19592271
TI  - Impact of Lennox-Gastaut Syndrome (LGS) on health-related quality of life (HRQL)
      of patients and caregivers: literature review.
AB  - The aim of this study was to conduct a review of the literature to evaluate the
      impact of LGS on the HRQL of children with LGS and their caregivers. The
      literature search revealed that there is limited published research on the impact
      of LGS on the HRQL of the child or caregiver. LGS has a major physical impact on
      a child, with a high frequency of seizures, and a high rate of seizure-related
      injuries. It interferes with all aspects of the child's intellectual and social
      development. The patient, and also his/her entire family are affected. Caring for
      a child with LGS is described as a 'burden', with increased anxiety about injury
      from seizures as well as the strain associated with providing continuous care.
      Overall, there is a lack of research on LGS, specifically the extent of the
      impact of LGS on the HRQL of the child and caregiver is under-explored.

PMID- 19592273
TI  - Deltex1 is a target of the transcription factor NFAT that promotes T cell anergy.
AB  - The molecular process underlying T cell anergy is incompletely understood.
      Deltex1 (DTX1) is a Notch target with unknown physiological function. Here we
      show that Dtx1 was a transcription target of nuclear factor of activated T cells
      (NFAT) and participated in T cell anergy. DTX1 protein was upregulated during T
      cell anergy, and transgenic expression of Dtx1 attenuated T cell activation. DTX1
      inhibited T cell activation by both E3-dependent and E3-independent mechanisms.
      In addition, DTX1 suppressed T cell activation in the absence of its Notch
      binding domain. Importantly, DTX1 regulated the expression of two anergy
      associated molecules, growth arrest and DNA-damage-inducible 45 beta (Gadd45
      beta) and Cbl-b. DTX1 interacted with early growth response 2 (Egr-2) for optimum
      expression of Cbl-b. Furthermore, deficiency of DTX1 augmented T cell activation,
      conferred resistance to anergy induction, enhanced autoantibody generation, and
      increased inflammation. DTX1 therefore represents a component downstream of
      calcium-NFAT signaling that regulates T cell anergy.

PMID- 19592272
TI  - Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic
      immune synapses.
AB  - Cytotoxic lymphocytes kill target cells by releasing the content of secretory
      lysosomes at the immune synapse. To understand the dynamics and control of
      cytotoxic immune synapses, we imaged human primary, live natural killer cells on
      lipid bilayers carrying ligands of activation receptors. Formation of an
      organized synapse was dependent on the presence of the beta2 integrin ligand ICAM
      1. Ligands of coactivation receptors 2B4 and NKG2D segregated into central and
      peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed
      during degranulation accumulated in a large and spatially stable cluster, which
      overlapped with a site of membrane internalization. Lysosomal compartments
      reached the plasma membrane at focal points adjacent to centrally accumulated
      LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were
      juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved.
      Thus, cytotoxic immune synapses include a central region of bidirectional
      vesicular traffic, which is controlled by integrin signaling.

PMID- 19592274
TI  - T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape
      the iNKT cell repertoire.
AB  - Mouse type I natural killer T cell receptors (iNKT TCRs) use a single V alpha 14
      J alpha 18 sequence and V beta s that are almost always V beta 8.2, V beta 7, or
      V beta 2, although the basis of this differential usage is unclear. We showed
      that the V beta bias occurred as a consequence of the CDR2 beta loops determining
      the affinity of the iNKT TCR for CD1d-glycolipids, thus controlling positive
      selection. Within a conserved iNKT-TCR-CD1d docking framework, these inherent V
      beta-CD1d affinities are further modulated by the hypervariable CDR3 beta loop,
      thereby defining a functional interplay between the two iNKT TCR CDR beta loops.
      These V beta biases revealed a broadly hierarchical response in which V beta 8.2
      > V beta 7 > V beta 2 in the recognition of diverse CD1d ligands. This
      restriction of the iNKT TCR repertoire during thymic selection paradoxically
      ensures that each peripheral iNKT cell recognizes a similar spectrum of antigens.

PMID- 19592278
TI  - Isolated transient neonatal clitoromegaly with hyperandrogenism of unknown
      etiology.
AB  - BACKGROUND: Neonatal clitoromegaly is usually attributed to androgen stimulation
      secondary to congenital adrenal hyperplasia or in utero androgen exposure. We
      present a unique case of transient, isolated neonatal clitoromegaly, associated
      with increased androgen levels of unidentifiable cause, which spontaneously
      resolved when the androgen levels normalized. This is the first report where,
      despite an exhaustive workup, the cause of hyperandrogenism remains unknown.
      CASE: A female infant was delivered at 25 + 5 weeks gestational age.
      Clitoromegaly was first documented at 3 months of age (18 mm long, |13 mm wide).
      There was no other evidence of virilization. There was no neonatal history of
      transfusions or androgen-medication exposure. Initial bloodwork documented
      extremely high levels of free testosterone (117 pmol/L) and
      dehydroepiandrosterone sulfate (DHEAS). Further tests ruled out the following
      diagnoses: 21-hydroxylase deficiency, 11-betahydroxylase deficiency, testicular
      feminization, presence of ovotesticular tissue, and androgen-secreting tumors.
      Maternal history ruled out in utero androgen exposure, maternal drug use,
      hyperandrogenism, or virilization during pregnancy, and antenatal imaging had not
      detected a maternal ovarian mass or adrenal tumor. The infant's androgen levels
      spontaneously declined, and by 4 months of age had normalized without therapy
      (free testosterone 8 pmol/L). At 5 months of age, the clitoral measurements
      normalized (10mm long, 5mm wide). CONCLUSION: In this case of a premature female
      infant, hyperandrogenism and clitoromegaly resolved spontaneously. Only 1 other
      case of hyperandrogenism and clitoromegaly that resolved spontaneously in a
      preterm infant has been reported. In that case, the clitoromegaly and high
      testosterone levels were attributed to repeated blood transfusions from an adult
      male. The etiology of the hyperandrogenism and resultant clitoromegaly in our
      case is not known.

PMID- 19592276
TI  - Human dendritic cells induce the differentiation of interleukin-21-producing T
      follicular helper-like cells through interleukin-12.
AB  - T follicular helper (Tfh) cells help development of antibody responses via
      interleukin-21 (IL-21). Here we show that activated human dendritic cells (DCs)
      induced naive CD4(+) T cells to become IL-21-producing Tfh-like cells through IL
      12. CD4(+) T cells primed with IL-12 induced B cells to produce immunoglobulins
      in a fashion dependent on IL-21 and inducible costimulator (ICOS), thus sharing
      fundamental characteristics with Tfh cells. The induction of Tfh-like cells by
      activated DCs was inhibited by neutralizing IL-12. IL-12 induced two different IL
      21-producers: IL-21(+)IFN-gamma(+)T-bet(+) Th1 cells and IL-21(+)IFN-gamma(-)T
      bet(-) non-Th1 cells, in a manner dependent on signal transducer and activator of
      transcription 4 (STAT4). IL-12 also regulated IL-21 secretion by memory CD4(+) T
      cells. Thus, IL-12 produced by activated DCs regulates antibody responses via
      developing IL-21-producing Tfh-like cells and inducing IL-21 secretion from
      memory CD4(+) T cells. These data suggest that the developmental pathway of Tfh
      cells differs between mice and humans, which have considerable implications for
      vaccine development.

PMID- 19592277
TI  - KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine
      production and upregulation of bystander chemokine receptors.
AB  - The transcription factor KLF2 regulates T cell trafficking by promoting
      expression of the lipid-binding receptor S1P(1) and the selectin CD62L. Recently,
      it was proposed that KLF2 also represses the expression of chemokine receptors.
      We confirmed the upregulation of the chemokine receptor CXCR3 on KLF2-deficient T
      cells. However, we showed that this was a cell-nonautonomous effect, as revealed
      by CXCR3 upregulation on wild-type bystander cells in mixed bone-marrow chimeras
      with KLF2-deficient cells. Furthermore, KLF2-deficient T cells overproduced IL-4,
      leading to the upregulation of CXCR3 through an IL-4-receptor- and eomesodermin
      dependent pathway. Consistent with the increased IL-4 production, we found high
      concentrations of serum IgE in mice with T cell-specific KLF2 deficiency. Our
      findings support a model where KLF2 regulates T cell trafficking by direct
      regulation of S1P(1) and CD62L and restrains spontaneous cytokine production in
      naive T cells.

PMID- 19592275
TI  - Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and
      V beta 7 semi-invariant NKT T cell receptors.
AB  - The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid
      antigens. Although the TCR alpha chain is typically invariant, the beta chain
      expression is more diverse, where three V beta chains are commonly expressed in
      mice. We report the structures of V alpha 14-V beta 8.2 and V alpha 14-V beta 7
      NKT TCRs in complex with CD1d-alpha-galactosylceramide (alpha-GalCer) and the 2.5
      A structure of the human NKT TCR-CD1d-alpha-GalCer complex. Both V beta 8.2 and V
      beta 7 NKT TCRs and the human NKT TCR ligated CD1d-alpha-GalCer in a similar
      manner, highlighting the evolutionarily conserved interaction. However,
      differences within the V beta domains of the V beta 8.2 and V beta 7 NKT TCR-CD1d
      complexes resulted in altered TCR beta-CD1d-mediated contacts and modulated
      recognition mediated by the invariant alpha chain. Mutagenesis studies revealed
      the differing contributions of V beta 8.2 and V beta 7 residues within the CDR2
      beta loop in mediating contacts with CD1d. Collectively we provide a structural
      basis for the differential NKT TCR V beta usage in NKT cells.

PMID- 19592279
TI  - Associations between depressive symptoms and sexual risk behavior in a diverse
      sample of female adolescents.
AB  - STUDY OBJECTIVE: To determine associations between depressive symptoms, locus of
      control, and sexual outcomes in a predominantly African-American cohort of female
      adolescents. DESIGN: A computerized assessment was administered to participants
      as part of a larger randomized clinical trial. We assessed sexual risk behaviors
      (SRBs) via self-report, and we assessed depressive symptoms using the Center for
      Epidemiologic Studies Depression Scale. We used multivariate regression to
      determine associations between depressive symptoms and outcomes while controlling
      for covariates. SETTING: This was a secondary analysis of baseline data collected
      during a randomized clinical trial intended to prevent unintended pregnancy and
      sexually transmitted infections (STIs). PARTICIPANTS: 572 adolescent females,
      ages 13 to 21 years, were recruited via a hospital-based adolescent clinic and
      community-wide advertisements. MAIN OUTCOME MEASURES: Participants reported on
      prior sexual intercourse, number of lifetime partners, frequency of intercourse,
      history of pregnancies and STIs, and locus of control. RESULTS: Two thirds of the
      sample had been sexually active. In a model that controlled for all covariates,
      those with a high level of depressive symptoms had higher odds of having had
      intercourse (adjusted OR = 2.29; 95% CI = 1.18-4.43). High levels of depressive
      symptoms were also independently associated with increased numbers of lifetime
      sexual partners and an external locus of control. However, when depression and
      locus of control were included in the same model, locus of control was not
      independently associated with SRBs. CONCLUSION: These findings support other
      literature demonstrating an association between depression and SRBs, particularly
      in a largely African-American population. They further suggest that perceived
      control does not fully explain the relationship between depression and SRBs.

PMID- 19592281
TI  - Cervical dysplasia and associated risk factors in a juvenile detainee population.
AB  - STUDY OBJECTIVE: Canada has licensed a human papilloma virus (HPV) vaccine for
      adolescent females, with the goal of decreasing the incidence of HPV infection
      and associated cervical cancer. This study identifies the juvenile detainee
      population as a high-risk group for HPV infection and therefore an important
      target for primary prevention. DESIGN: A retrospective chart review. SETTING:
      Sundance Juvenile Detention Center, Kingston, Ontario, Canada. PARTICIPANTS:
      Female detainees admitted between 2003 and 2006. MAIN OUTCOME MEASURES:
      Papanicolaou (Pap) test results, sexually transmitted infection (STI) rates, and
      associated risk factors were collected from 119 charts. RESULTS: Of 57 recorded
      Pap smears, 46 (80.7%) were normal, 5 (8.8%) were reported as atypical squamous
      cells of unknown significance, and 6 (10.5%) were reported as low-grade squamous
      intraepithelial lesion. Of the women tested, 4% were positive for gonorrhea, 10%
      for chlamydia, 32% for bacterial vaginosis, and 5% for trichomonas; none were
      positive for syphilis. Of the girls, (91) (77%) had negative HIV and hepatitis B
      tests, two girls were hepatitis-C-positive, three had clinical evidence of
      genital herpes, and one showed evidence of pelvic inflammatory disease. There
      were 75 (63%) girls who reported sexual activity; 87% of them used contraception
      or protection of some kind, albeit inconsistently. Of these young females, 12
      (10%) had engaged in prostitution and 13 (11%) had allegedly been raped or
      sexually assaulted. CONCLUSIONS: Female juvenile detainees in Kingston, Ontario,
      have higher rates of STIs, associated risk factors, and abnormal Pap tests than
      the general female adolescent population. This new information confirms that this
      population is at risk for HPV infection and subsequent cervical cancer.

PMID- 19592280
TI  - Relationship context associated with microbicide-like product use.
AB  - STUDY OBJECTIVE: Topical microbicides are being developed to provide an
      alternative method of prevention of HIV and sexually transmitted infections.
      Although topical microbicides would be a female-controlled method of prevention,
      their use is likely to be disclosed to partners. Thus, the characteristics of the
      partner relationship may play a role in their use. We sought to examine whether
      qualities of the relationship and of the partner were associated with using a
      microbicide-like product. DESIGN: We studied 166 females (14 to 21 years of age)
      who were participating in a 6-month study of microbicide-like products (vaginal
      lubricants). They described partner relationships and characteristics of the
      partners. RESULTS: Of the 166 participants, 118 used the product. In bivariate
      analyses, those whose relationships were longer, monogamous, more mutual, and
      more satisfying were more likely to use the product. Further, when sex occurred
      in the young women's or couples' homes, use also was more likely. There was no
      relationship between product use and whether the partner had a job or was in
      school or between the partners' levels of substance use. In a multivariable
      logistic regression with backwards elimination, only relationship satisfaction
      remained significant in the model. CONCLUSION: Topical microbicides will be used
      within the context of a relationship, and characteristics of the relationship
      most likely will influence use. These findings suggest that special attention may
      have to be given to supporting use in high-risk relationships and that all
      interventions to enhance uptake should consider the relationship context.

PMID- 19592282
TI  - Semi-dominant X-chromosome linked learning disability with progressive ataxia,
      spasticity and dystonia associated with the novel MECP2 variant p.V122A: akin to
      the new MECP2 duplication syndrome?
AB  - A novel X-chromosome linked phenotype is reported. Three affected males had
      learning disability in early childhood and subsequently developed progressive
      ataxia, dystonia, and spasticity with death at ages 9, 14 and 19 years. Two
      female obligate carriers had learning difficulties with psychosis in one case. A
      third, possible carrier had learning difficulties and epilepsy. A family study
      indicates that this inherited syndrome is most likely due to an unreported MECP2
      variant, p.V122A, located in the methyl binding domain of the MECP2 protein. The
      clinical features are similar to those present in the newly reported MECP2
      duplication syndrome. Non-progressive neuropsychiatric symptoms in female
      relatives of a male child with learning disability, ataxia and progressive
      spasticity may constitute a clue to inherited, MECP2 pathogenesis.

PMID- 19592283
TI  - The INPHARMA technique for pharmacophore mapping: A theoretical guide to the
      method.
AB  - During the process of drug discovery, INPHARMA can be used to derive the
      structure of receptor/lead compound complexes binding to each other with a K(d)
      in the microM to mM range. To be successful, the methodology needs adjustment of
      various parameters that depend on the physical constants of the binding event and
      on the receptor size. Here we present a thorough theoretical analysis of the
      INPHARMA interligand NOE effect in dependence of experimental parameters and
      physical constants. This analysis helps the experimentalist to choose the correct
      experimental parameters and consequentially to achieve optimal performance of the
      methodology.

PMID- 19592284
TI  - Quantitative ultrasound of the calcaneus in greek women: normative data are
      different from the manufacturer's normal range.
AB  - Quantitative ultrasound (QUS) is considered a useful method in evaluating bone
      status. The aim of the present study was to establish the reference data for the
      QUS measurements of the calcaneus in a Greek population. We measured a QUS
      parameter, stiffness index (SI), at the right calcaneus in 1500 women using the
      Achilles express Ultrasonometer (GE Lunar, Madison, WI). Participants were
      divided into 7 groups according to their age with a 10-yr span in each group. A
      progressive decline was found in the SI values after the age of 39 yr in the
      current study. When the SI values were compared between the age groups, high
      statistically significant differences were obvious, especially between 20-29 and
      50- to 59-yr age groups and 60-69 and 70- to 79-yr age groups (p < 0.0005).
      Additionally, in the Greek normal range (GNR), the SI values of those aged 60-69
      and 70-79 yr were significantly higher (81.84+/-16.14 and 77.45+/-17.65,
      respectively) than those in the manufacturer's normal range (MNR; 75.84+/-16.14
      and 69.10+/-17.65, p < 0.005, respectively). Using the manufacturer's values,
      significantly fewer women were classified as normal (48% vs 67.3%), although
      those with T-score < or =-2.5 were more (15.7%) compared with our Greek value
      (1.5%), and classification of subjects into risk-of-fracture categories was
      significantly different (kappa: 0.459, 66.2%, p < 0.0005). Multiple regression
      analysis showed that weight was the most significant predictor for SI in the age
      groups 30-39 (beta = 0.280, p < 0.05), 40-49, 60-69, and 70-79 yr (beta = 0.185,
      p < 0.005; beta = 0.329, p < 0.0005; beta = 0.494, p<0.0005, respectively). Using
      conventional categories of risk, we report a different classification of our
      subjects from those proposed by the manufacturer, supporting the concept that
      data specific to the Greek population are necessary.

PMID- 19592286
TI  - Intensive blood glucose control is safe and effective in diabetic cats using home
      monitoring and treatment with glargine.
AB  - Human diabetic patients routinely self-adjust their insulin dose using a protocol
      and home monitoring, and perform equally well or outperform physician directed
      adjustments. The objective of this study was to report the outcome of home
      monitoring of diabetic cats by owners using a protocol aimed at achieving
      euglycaemia, using ultra-low carbohydrate diets (< or =10% metabolisable energy)
      and the insulin analogue glargine for >10 weeks and/or until remission was
      achieved. Fifty-five cats diagnosed with diabetes mellitus, whose owners joined
      the online German Diabetes-Katzen Forum, were included. An overall remission rate
      of 64% was achieved in the cohort. Significantly higher remission rates were
      observed if good glycaemic control was achieved soon after diagnosis: 84% for
      cats started on the protocol within 6 months of diagnosis went into remission,
      and only 35% for cats that began more than 6 months after diagnosis (P<0.001).
      Only one mild clinical hypoglycaemic episode occurred observed despite tight
      blood glucose control. In conclusion, intensive blood glucose control is safe and
      effective in diabetic cats using home monitoring and treatment with glargine.

PMID- 19592285
TI  - Systemic hypertension in two patients with ASL deficiency: a result of nitric
      oxide deficiency?
AB  - Argininosuccinic aciduria (ASA) is an inborn error of ureagenesis which if
      untreated leads to hyperammonemia, accumulation of argininosuccinic acid and
      arginine depletion. The presence of high blood pressure in patients with ASA has
      been reported so far as transient in one newborn. We describe the first two
      patients, one child and one young adult, with ASA and persistent systemic
      hypertension. Extensive evaluation of both patients excluded secondary causes of
      systemic hypertension. The intriguing link between nitric oxide (NO) production
      and hypertension lead us to hypothesize that the deficiency of endogenously
      synthesized arginine caused by ASL deficiency is responsible for the increased
      blood pressure.

PMID- 19592287
TI  - Spontaneous rupture of the flexor digitorum superficialis tendon of the index and
      middle fingers: "the pen sign".
AB  - We report this case of a flexor digitorum superficialis (FDS) tendon rupture of
      the second and third fingers of the right hand in a 46-year-old patient. This
      rupture seems to occur under moderate stress. In this precise situation, the
      diagnosis was confirmed from the MRI data. Treatment was entirely conservative.
      However, the clinical presentation of the patient appeared quite original and so
      misleading to us that we reported this case here and developed the term "pen
      sign" to describe it. Considering this case, in order to reanimate thumb flexion
      transferring the fourth finger, FDS would appear to be entirely justified because
      of the lack of consequent difficulties on fine thumb index finger grasping used
      when holding pens or fine tweezers. It should also lead us in our everyday
      surgical practice to attempt to systematically repair the two index flexor
      tendons when they are damaged.

PMID- 19592288
TI  - Acid-induced gelation behavior of sonicated casein solutions.
AB  - Casein gels were made from solutions sonicated by 24 and 130 kHz ultrasounds for
      0, 60 and 120 min, followed by acidification with glucono-delta-lactone at 30
      degrees C. The dynamics of gel formation were studied using rheological methods
      and microstructure of gels was monitored using scanning electron microscopy.
      Sonication postponed the gelation point to a lower pH value and increased the
      elasticity of freshly formed gels. It also resulted in gels with a more
      interconnected structure and smaller non-distinguishable particulates. This
      structure was especially dominant for the gel made from the solution already
      sonicated for 120 min.

PMID- 19592289
TI  - Degradation of fenitrothion by ultrasound/ferrioxalate/UV system.
AB  - The sonochemical photodegradation of fenitrothion, which is one of
      phosphorothiate insecticides, was carried out in the presence of Fe(III) and
      oxalate. The degradation rate was strongly influenced by initial concentrations
      of Fe(III) and oxalate. An initial fenitrothion concentration of 10 mg L(-1) was
      completely degraded after 30 min at pH 6 under the optimum conditions. Therefore,
      the photo-Fenton reaction combined with sonication in the presence of oxalate was
      available around neutral pH. The decrease of TOC as a result of mineralization of
      fenitrothion was observed during ultrasound (US)/ferrioxalate/UV process. In
      addition, the formations of nitrite and sulfate ions as end-products were
      observed during this degradation system. The decomposition of fenitrothion gave
      two kinds of intermediate products. The degradation mechanism of fenitrothion was
      proposed on the base of the evidence of the identified intermediates. Based on
      these results, US/ferrioxalate/UV system could be useful technology for the
      treatment of wastewater containing fenitrothion.

PMID- 19592290
TI  - Assessment of four statistical pattern recognition techniques to assist in
      obstructive sleep apnoea diagnosis from nocturnal oximetry.
AB  - The aim of this study is to assess the utility of traditional statistical pattern
      recognition techniques to help in obstructive sleep apnoea (OSA) diagnosis.
      Classifiers based on quadratic (QDA) and linear (LDA) discriminant analysis, K
      nearest neighbours (KNN) and logistic regression (LR) were evaluated. Spectral
      and nonlinear input features from oxygen saturation (SaO(2)) signals were
      applied. A total of 187 recordings from patients suspected of suffering from OSA
      were available. This initial dataset was divided into training set (74 subjects)
      and test set (113 subjects). Twelve classification algorithms were developed by
      applying QDA, LDA, KNN and LR with spectral features, nonlinear features and
      combination of both groups. The performance of each algorithm was measured on the
      test set by means of classification accuracy and receiver operating
      characteristic (ROC) analysis. QDA, LDA and LR showed better classification
      capability than KNN. The classifier based on LDA with spectral features provided
      the best diagnostic ability with an accuracy of 87.61% (91.05% sensitivity and
      82.61% specificity) and an area under the ROC curve (AROC) of 0.925. The proposed
      statistical pattern recognition techniques could be applied as an OSA screening
      tool.

PMID- 19592291
TI  - Selective image similarity measure for bronchoscope tracking based on image
      registration.
AB  - We propose a selective method of measurement for computing image similarities
      based on characteristic structure extraction and demonstrate its application to
      flexible endoscope navigation, in particular to a bronchoscope navigation system.
      Camera motion tracking is a fundamental function required for image-guided
      treatment or therapy systems. In recent years, an ultra-tiny electromagnetic
      sensor commercially became available, and many image-guided treatment or therapy
      systems use this sensor for tracking the camera position and orientation.
      However, due to space limitations, it is difficult to equip the tip of a
      bronchoscope with such a position sensor, especially in the case of ultra-thin
      bronchoscopes. Therefore, continuous image registration between real and virtual
      bronchoscopic images becomes an efficient tool for tracking the bronchoscope.
      Usually, image registration is done by calculating the image similarity between
      real and virtual bronchoscopic images. Since global schemes to measure image
      similarity, such as mutual information, squared gray-level difference, or cross
      correlation, average differences in intensity values over an entire region, they
      fail at tracking of scenes where less characteristic structures can be observed.
      The proposed method divides an entire image into a set of small subblocks and
      only selects those in which characteristic shapes are observed. Then image
      similarity is calculated within the selected subblocks. Selection is done by
      calculating feature values within each subblock. We applied our proposed method
      to eight pairs of chest X-ray CT images and bronchoscopic video images. The
      experimental results revealed that bronchoscope tracking using the proposed
      method could track up to 1600 consecutive bronchoscopic images (about 50s)
      without external position sensors. Tracking performance was greatly improved in
      comparison with a standard method utilizing squared gray-level differences of the
      entire images.

PMID- 19592292
TI  - Investigation of posterior corneal curvature in CL-induced corneal swelling.
AB  - PURPOSE: To evaluate Orbscan II measurements without contact lens (CL) removal to
      monitor in vivo posterior corneal curvature in CL (hypoxia)-induced corneal
      swelling during extended wear (EW). METHODS: Orbscan II corneal topographer was
      used to measure posterior corneal curvature 1 week before CL wearing and during 1
      week of EW. Central corneal thickness (CCT) was also measured during the 2-week
      study with OCT to determine the corneal swelling percentage. High Dk (lotrafilcon
      A) and low Dk (etafilcon A) soft CL were randomly fitted in EW in the right and
      left eyes of 20 subjects with normal ocular health. Orbscan and OCT were also
      performed without CL removal after 3 and 7 days of wear. RESULTS: Low Dk lenses
      induced significantly higher corneal swelling (2.41+/-2.65%), as compared to the
      high Dk lenses (0.17+/-2.28%; P<0.05 repeated measures ANOVA (Re-ANOVA and paired
      t-test) measures with OCT. The low Dk lens induced a significantly posterior
      corneal flattening compared to the high Dk lens (0.036+/-0.06mm versus 0.006+/
      0.04mm; P<0.05 Re-ANOVA and paired t-test). High repeatability for Orbscan
      measured posterior best fit sphere (BFS) radii with (r(2)=0.15, 95% limits of
      agreement (LoA)=0.10 to -0.06) and without (r(2)=0.00, 95% LoA=0.08 to -0.08) CL
      removal was also observed and suggest that posterior corneal changes was not due
      to Orbscan variability. CONCLUSIONS: Orbscan is a non-invasive and reproducible
      technique to evaluate and monitoring posterior corneal curvature in vivo in CL
      (hypoxia)-induced corneal swelling during EW.

PMID- 19592293
TI  - Effect of the acyl group and the dodecylsulfonate chain on the inclusion of
      pyrene inside the cavity of beta-cyclodextrin.
AB  - The solubilization of pyrene in aqueous solution of beta-cyclodextrin (beta-CD)
      or its derivatives such as beta-CD-hexanoyl, beta-CD-benzoyl and beta-CD
      dodecylsulfonate was investigated by spectrophotometry. Linear and non-linear
      regression methods were used to estimate the association constants (K(1)). A 1:1
      stoichiometric ratio and different effects of the hexanoyl, benzoyl and
      dodecylsulfonate groups on the association constant were observed for the binary
      inclusion complex between pyrene and beta-CD. The formation constant was shown to
      decrease when beta-CD was modified by a dodecylsulfonate chain. The value of K(1)
      was 190+/-10 L mol(-1) for the [pyrene/beta-CD] complex and 145 L mol(-1) for the
      [pyrene/beta-CD-dodecylsulfonate] complex. Partitioning of the pyrene molecules
      between the dodecylsulfonate chains and cyclodextrin cavities can explain the
      decrease in the association constant value. In the cases of beta-CD-hexanoyl and
      beta-CD-benzoyl derivatives, no association constants were detected. Results
      suggest that the high hydrophobicity of the hexanoyl and benzoyl groups prevents
      the inclusion of pyrene molecules inside the cyclodextrin cavity.

PMID- 19592294
TI  - Preparation, spectroscopic and high field NMR relaxometry studies of
      gadolinium(III) complexes with the asymmetric tetraamine 1,4,7,11
      tetraazaundecane.
AB  - The reaction of Gd(III) with asymmetric tetramine 1,4,7,11-tetraazaundecane
      (2,2,3-tet, L(1)) ligand has been studied via NMR spectroscopy. The ligand proton
      longitudinal relaxation rates (R(1)) have been used to estimate the distances of
      these protons from the Gd(III) center, in Gd(III)-L(1) reaction solutions, in
      H(2)O/D(2)O 5/1 mixtures. Two Gd(III) complexes
      [Gd(III)(L(1))(NH(3))(H(2)O)(4)](CH(3)COO)(3)*2H(2)O (1) and
      [Gd(III)(L(1))(NH(3))(H(2)O)(2)]Cl(3)*EtOH (2) have been isolated and
      characterized by elemental analyses, TGA, IR, NMR and relaxometry measurements.
      The NMR relaxation measurements of 2 in aqueous solutions have been performed,
      under various temperature or concentration conditions, and compared with those of
      the commercial contrast agents Gd(III)-DTPA and Gd(III)-DTPA-BMA. It has also
      been studied the influence of (i) the Gd(III) inner-sphere water molecule number
      (q) alteration and (ii) the steric constraint enhancement on the metal site, over
      the relaxation rate values of the parent aqueous solution of Gd(III)-2,2,3-tet,
      and of the aqueous solutions of 2.

PMID- 19592296
TI  - The interaction between atoms of Au and Cu with clean Si(111) surface: a study
      combining synchrotron radiation grazing incidence X-ray fluorescence analysis and
      theoretical calculations.
AB  - In order to evaluate the interactions between Au/Cu atoms and clean Si(111)
      surface, we used synchrotron radiation grazing incidence X-ray fluorescence
      analysis and theoretical calculations. Optimized geometries and energies on
      different adsorption sites indicate that the binding energies at different
      adsorption sites are high, suggesting a strong interaction between metal atom and
      silicon surface. The Au atom showed higher interaction than Cu atom. The
      theoretical and experimental data showed good agreement.

PMID- 19592295
TI  - Spectroscopic and antimicrobial studies of La3+, Pr3+, Nd3+ and Gd3+ complexes of
      a dipodal [N,N,N] chelating ligand.
AB  - The lanthanide complexes of bis(benzimidazole-2'-yl-methyl)amine (BImz) having
      molecular formula [M(BImz)X(3)H(2)O]*nH(2)O (M = La, Pr, Nd, or Gd; X = Cl or
      ClO(4) and n = 1, 2 or 3) were prepared and characterized spectroscopically
      through IR, (1)H and (13)C NMR, FAB-mass, UV-visible and luminescence
      spectroscopy. TGA data suggested presence of coordinated and the lattice water.
      The oscillator strengths of the f-f transitions and the covalency parameters
      (beta, b(1/2) and delta) have been evaluated from the electronic spectral data.
      The proposed hepta-coordinate geometry for the complexes has been ascertained
      from the molecular model computations. CV studies indicate formation of a stable
      quasi-reversible redox couple Gd(III/IV) in the solution. The in vivo
      antimicrobial activities of the complexes have been evaluated against gram +ve
      and gram -ve bacteria and fungi.

PMID- 19592297
TI  - A novel fluorescent distinguished probe for Cr (VI) in aqueous solution.
AB  - Salicylaldehyde rhodamine B hydrazone (SRBH) was developed as a new
      spectrofluorimetric probe for the selective and sensitive detection of CrO(4)(2-)
      in acidic conditions. The proposed method was based on the special oxidation
      reaction between non-fluorescent SRBH by potassium dichromate to produce a highly
      fluorescent rhodamine B, as a product. Under the optimum conditions described,
      the fluorescence enhancement at 591 nm was good linearly related to the
      concentration of CrO(4)(2-) from 1.0 x 10(-8) to 3.0 x 10(-7)M (0.42-12.6 ng mL(
      1)) with a correlation coefficient of R(2)=0.9989 (n=10) and a detection limit of
      1.5 x 10(-9)M (0.063 ng mL(-1)). The relative standard deviation (R.S.D.) was
      2.0% (n=6). The proposed method was also successfully applied to the
      determination of chromium (VI) in drinking water, river water and synthetic
      samples.

PMID- 19592298
TI  - Optical, dielectric and microhardness studies on (100) directed ADP crystal.
AB  - (100) directed ammonium dihydrogen phosphate single crystal has been grown using
      the uniaxially solution-crystallization method of Sankaranarayanan-Ramasamy (SR).
      The size of the grown crystal is 40 mm in diameter and 50mm in thickness. The
      grown crystals were characterized by UV-vis spectroscopy, Vickers hardness and
      dielectric studies. Comparing the (100) plane of the conventional method grown
      ADP crystal with (100) directed SR method grown ADP crystal, optical
      transparency, dielectric constant and Vickers hardness number are increased and
      dielectric loss is decreased in SR method grown crystal.

PMID- 19592299
TI  - In situ reverse-transcription loop-mediated isothermal amplification (in situ RT
      LAMP) for detection of Japanese encephalitis viral RNA in host cells.
AB  - BACKGROUND: Clinical diagnosis of Japanese encephalitis is usually difficult due
      to non-specific signs at the early and acute stages of the infection. Virus
      isolation from peripheral blood is also not possible because of the short period
      and low level of transient viremia even in the acute stage of the disease. It is
      thus urgent to develop a feasible and convenient method for laboratory diagnosis
      of the infection. OBJECTIVES: To establish a newly designed molecular approach
      that can be used to detect intracellular Japanese encephalitis viral RNA in host
      cells. STUDY DESIGN: The method was firstly established and then was carried out
      to test its efficacy in cultured BHK-21 cells, subsequently in peripheral blood
      mononuclear cells (PBMCs) isolated from mice that have been inoculated with JE
      virus suspension. RESULTS: In this study, in situ reverse-transcription loop
      mediated isothermal amplification (in situ RT-LAMP) was established; which
      combines merits of recently developed loop-mediated isothermal amplification
      (LAMP) and in situ reverse-transcriptase polymerase chain reaction (in situ RT
      PCR). CONCLUSIONS: The newly designed method can detect viral RNAs in peripheral
      blood mononuclear cells (PBMCs) in a short time with high sensitivity and
      efficiency.

PMID- 19592300
TI  - Obstructive sleep apnea as a cause of nocturnal eating.

PMID- 19592301
TI  - Follow-up PET studies in case of idiopathic REM sleep behavior disorder.

PMID- 19592302
TI  - Pregnancy accounts for most of the gender difference in prevalence of familial
      RLS.
AB  - OBJECTIVE: This study was designed to evaluate the associated risk of RLS with
      pregnancy in relation to the family history and the age of symptom onset of RLS.
      METHODS AND SUBJECTS: Data from a prior RLS family history study in which 1019
      subjects (527 males, 492 females) were interviewed, provided a diagnosis and
      characterization of RLS and determination of pregnancy status on which the
      current study analysis was undertaken. RESULTS: In the family members of RLS
      probands, the prevalence of RLS was significantly higher for parous women than
      for nulliparous women (49.5% vs. 33.7%, OR=1.92, 95% CI=1.16-3.19) or for men
      (49.5% vs. 30.0%, OR 2.29, 1.69-3.10), but no different for nulliparous women
      compared to men (33.7% vs. 30.0%, OR 1.19, 0.72-1.96). When only those whose RLS
      started at or after age 30 were considered, similar differences occurred. These
      differences were not observed among family members of control probands.
      CONCLUSIONS: These data indicate pregnancy has a major impact on the risk of
      developing RLS for those with a family history of RLS. This pregnancy effect
      appears to account for most of the gender differences often reported in overall
      RLS prevalence data.

PMID- 19592303
TI  - Sleep duration, insomnia and longevity.

PMID- 19592305
TI  - Motor fitness in Dutch youth: differences over a 26-year period (1980-2006).
AB  - This study aimed to compare neuromotor fitness test scores of 9-12-year-old Dutch
      youth in 2006 with scores of same aged children in 1980. Body height, body weight
      and performance on neuromotor fitness test items were measured in 2050 Dutch
      children from 9 to 12 years in 2006 and were compared with data of 2603 same aged
      Dutch children measured in 1980 with the same neuromotor fitness test battery.
      Dutch 9-12 year olds in 2006 were significantly taller and heavier than their
      peers in 1980. Age- and sex-specific performance on almost all neuromotor fitness
      test items was significantly worse in 2006. Thus, our data suggest that
      neuromotor fitness of Dutch youth has significantly decreased over the past 26
      years.

PMID- 19592306
TI  - 46, XY female with cloacal exstrophy and masculinization at puberty.
AB  - Cloacal exstrophy of the bladder is a rare complex disorder occurring 1 in
      400,000 live births and associated with cryptorchidism, vesicoureteral reflux,
      severe phallic inadequacy, omphalocele with short-gut syndrome, exstrophied
      bladder separated by exstrophied ileocecal segment, and pubic symphyseal
      diastasis. The association of undescended and ectopic testis with cloacal
      exstrophy is not uncommon, but the presence of an unexpected persistent ectopic
      testis at the time of puberty is quite unusual. We report the case of a 17-year
      old girl with a history of 46, XY cloacal exstrophy and gender reassignment
      presenting with an ectopic testis of unclear location. We then review
      controversial literature surrounding gender assignment in these patients.

PMID- 19592304
TI  - Peduncular hallucinosis: a polysomnographic and spect study of a patient and
      efficacy of serotonergic therapy.
AB  - Peduncular hallucinosis (PH) consists of formed and coloured visual images, which
      the patient knows are unreal; it is often associated with lesions of the pons,
      midbrain and diencephalon. A 72-year-old man had noted the sudden onset of visual
      hallucinations one year before, specifying the time and body position in a 4
      week, 24-h diary. Thereafter, he underwent video-polysomnography (VPSG), brain
      magnetic resonance imaging (MRI), angiography (MRA), proton spectroscopy ((1)H
      MRS), and single photon emission tomography (SPECT). Patient's diaries and VPSG
      showed a strong clustering of hallucinatory experiences during the evening/night
      time while lying in supine position, similar to hypnagogic hallucination and
      sleep paralysis in supine position. Repeated episodes of REM sleep behaviour
      disorder (RBD) occurred during the night. MRI and MRA showed an elongated and
      dilated left internal carotid artery displacing the left subthalamus upwards, and
      (1)H MRS relatively decreased N-acetyl-aspartate in the left subthalamus. Brain
      SPECT during PH revealed hypoperfusion in the right temporal region and
      hyperperfusion in the left occipital and right opercular regions (the latter
      possibly related to the patient's awareness of unreality). PH resolved with
      serotonergic (citalopram) therapy.

PMID- 19592307
TI  - Exploration of the extent of somato-sensory impairment in patients with
      unilateral lateral epicondylalgia.
AB  - There is evidence suggesting an important role of nociceptive sensitization in
      lateral epicondylalgia (LE). Our aim was to explore somato-sensory changes in
      patients with unilateral LE to better understand this musculoskeletal condition.
      Twelve patients (6 female) with LE with a mean (SD) age 47 (10) years, and 16
      controls (7 female), aged 41 (9) years were tested. The following somato-sensory
      parameters were assessed: pressure-pain threshold (PPT), heat- and cold-pain
      thresholds, thermal, cold- and vibration-detection thresholds. All these tests
      were bilaterally assessed over the lateral epicondyle (affected/unaffected in
      patients; dominant/nondominant in controls) and at the dorsal-lateral surface of
      the wrist in all patients and controls. The results showed that patients with
      unilateral LE not only exhibited substantial reductions in PPT on the affected
      side compared to the unaffected side (mean difference and 95% confidence
      intervals: 219 kPa [136.8 to 301.1 kPa] but also when compared to controls (581.1
      kPa [340.5 to 821.7 kPa]), showing bilateral pressure-pain hyperalgesia. These
      differences represented an effect size (ie, standardized mean difference) of 1.23
      and .94, respectively. In the same cohort, there were no such deficits in cold
      and heat pain, cold- and warm-detection thresholds, and vibration-detection
      thresholds, either between affected and unaffected sides in patients with LE or
      between patients and controls. Effect sizes for the sensory-detection tests were
      small, which were generally less than the pain tests. Our data imply that LE is
      largely characterized by peripheral and central mechanical pain hyperalgesia.
      PERSPECTIVE: This article reveals the presence of bilateral pressure-pain
      hypersensitivity in patients with unilateral LE. On the contrary, thermal and
      vibration tests were not significantly different from controls.

PMID- 19592308
TI  - Acidic saline-induced primary and secondary mechanical hyperalgesia in mice.
AB  - Most of our knowledge about chronic musculoskeletal pain is based on cutaneous
      pain models. To test the hypothesis that animals develop chronic muscular
      hyperalgesia following intramuscular acidic saline injections, primary
      hyperalgesia within the gastrocnemius muscle was analyzed compared to secondary
      cutaneous hyperalgesia in the hind paw that develops following intramuscular acid
      saline injection. Two acidic saline (pH 4) injections were administrated into the
      gastrocnemius of female CF-1 mice. The results indicate that mice developed a
      robust hypersensitivity bilaterally in primary (gastrocnemius muscle) secondary
      (cutaneous hind paw) sites that lasted up to 2 weeks. In addition, primary
      hyperalgesia correlated well with levels of Fos expression. Fos expression
      patterns in the spinal cord were different for primary secondary site
      stimulation. Hind-paw palpation stimulated ipsilateral Fos expression in the
      superficial spinal laminae at L4/L5 levels, bilaterally in deep laminae at L2-L5
      spinal levels. In contrast, gastrocnemius compression stimulated widespread Fos
      expression in all regions of the ipsilateral dorsal horn within L2-L6 spinal
      segments. These findings indicate that acidic saline injection induces primary
      hyperalgesia in muscle that the patterns of Fos expression in response to primary
      vs secondary stimulation are strikingly different. PERSPECTIVE: This study
      assesses primary site muscular pain, which is the main complaint of people with
      musculoskeletal conditions, and identifies spinal patterns activated by noxious
      mechanical stimuli to the gastrocnemius. This study demonstrates approaches to
      test nociception arising from muscle aids in our understanding of spinal
      processing of primary secondary site hyperalgesia.

PMID- 19592309
TI  - Bilateral widespread mechanical pain sensitivity in women with myofascial
      temporomandibular disorder: evidence of impairment in central nociceptive
      processing.
AB  - Our aim was to investigate bilateral, widespread pressure-pain hypersensitivity
      in nerve, muscle, and joint tissues in women with myofascial temporomandibular
      disorders (TMD) without concomitant comorbid conditions. Twenty women with
      myofascial TMD (aged 20 to 28 years old), and 20 healthy matched women (aged 20
      to 29 years), were recruited. Pressure-pain thresholds (PPT) were bilaterally
      assessed over supra-orbital (V1), infra-orbital (V2), mental (V3) nerves, median
      (C5), radial (C6) and ulnar (C7) nerve trunks, the C5-C6 zygapophyseal joint, the
      lateral pole of the temporo mandibular joint (TMJ), and the tibialis anterior
      muscle in a blinded design. The results showed that PPTs were significantly
      decreased bilaterally over the supra-orbital, infra-orbital, and mental nerves,
      median, ulnar, and radial nerve trunks, the lateral pole of the TMJ, the C5-C6
      zygapophyseal joint, and the tibialis anterior muscle in patients with myofascial
      TMD as compared to healthy controls (all sites: P < .001). There were no
      significant differences in the magnitude of PPT decreases between the trigeminal
      and extratrigeminal test sites. PPT over the mental nerve, the TMJ, C5-C6
      zygapophyseal joint and tibialis anterior muscle were negatively correlated to
      both duration of pain symptoms and TMD pain intensity (P < .05). Our findings
      revealed bilateral, widespread pressure hypersensitivity in women presenting with
      myofascial TMD, suggesting that widespread central sensitization is involved in
      myofascial TMD women. PERSPECTIVE: This article reveals the presence of bilateral
      and widespread pressure-pain hypersensitivity in women with myofascial TMD,
      suggesting that widespread central sensitization is involved in myofascial TMD.
      This finding has implications for development of management strategies.

PMID- 19592311
TI  - Disease progression meta-analysis model in Alzheimer's disease.
AB  - BACKGROUND: Various authors have evaluated disease progression in Alzheimer's
      disease (AD), using patient data from individual clinical studies or pooled data
      across various trials. We conducted a systematic review of public data sources
      from 1990 to 2008 for all available AChE inhibitor studies, as well as clinical
      studies that evaluated the rate of deterioration in AD patients. Unique to this
      analysis, we developed a model based on literature data to describe the
      longitudinal response in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS
      cog) (change from baseline) in mild to moderate severity AD patients. The model
      was used to estimate disease progression for both placebo-treated patients and
      acetylcholinesterase (AChE)-inhibitor treated patients, and factors that affected
      disease progression. METHODS: We collected 576 mean ADAS-cog changes from
      baseline data points of 52 trials, representing data from approximately 19,972
      patients and more than 84,000 individual observations. The model described the
      rate of disease progression, the evident placebo effect, and the symptomatic
      effect of AChE-inhibitors. Baseline ADAS-cog, Mini-Mental State Examination
      score, age, and year of publication were tested as covariates. RESULTS: The
      disease progression in mild to moderate AD patients across all available and
      relevant literature sources was estimated as 5.5 points per year. An Emax-type
      model best described the symptomatic drug effect of AChE inhibitors. The rate of
      disease progression (underlying disease progression) was no different between
      placebo and AChE-inhibitors groups. Baseline ADAS-cog is a significant covariate
      in disease progression. Baseline age was also tested as a covariate in the rate
      of disease progression, but the model was unable to describe any effects of age,
      likely because of the narrow distribution of mean age (literature-level
      analysis). There was no significant impact of publication year in the model.
      CONCLUSIONS: Baseline ADAS-cog is a significant covariate affecting the rate of
      disease progression, and it describes or at least explains the different rates of
      deterioration evident in early or late stages of the disease. There was no
      significant impact of publication year in the model, suggesting that disease
      progression has not slowed in more recent trials.

PMID- 19592310
TI  - A multicenter, open-label, exploratory dose-ranging trial of intranasal
      hydromorphone for managing acute pain from traumatic injury.
AB  - We conducted a prospective multicenter, open-label, escalating dose-range trial
      to compare, across patients, single intranasal doses (2, 4, 6, 8, and 10 mg) of
      hydromorphone HCl in the treatment of acute trauma pain The main outcome measure
      of pain-intensity reduction was derived from serial Numerical Pain-Rating Scores
      and calculated as the summed pain-intensity difference over 3 hours (SPID 3).
      Nasal examinations, vital signs, and adverse events were reported as safety
      outcomes. The mean decrease in pain intensity from baseline to 30 minutes was 39
      to 44% for the 4-, 6-, 8- and 10-mg doses (n = 19, 33, 28, and 19 per group) and
      only 24% reduction for the 2-mg dose (n = 14). SPID 3 for the 2-mg dose was 40 to
      50% below all other doses. There were no clinically meaningful changes in vital
      signs or nasal examinations. Adverse events (nausea, vomiting, pruritus, oxygen
      desaturation, bad taste, dizziness) were of mild to moderate intensity, increased
      with dose, and expected, based on route of administration and opioid
      pharmacology. Intranasal hydromorphone provides a component of rapid pain relief
      in the care of emergency department patients suffering from acute trauma pain.
      PERSPECTIVE: This article presents a pilot dose-ranging study of intranasally
      administered hydromorphone, administered in the emergency department to patients
      suffering from acute trauma pain. This study demonstrates research success in
      this setting and noninjection-based delivery and certain doses of intranasal
      hydromorphone may be effective in treating acute trauma pain.

PMID- 19592312
TI  - Effect of temporal relationship between respiration and body motion on motion
      sickness.
AB  - BACKGROUND: This study investigated the effect controlling the phase of
      respiration on the development of nausea provoked by periodic motion at 0.2 Hz
      which is maximal for provocation of motion sickness. METHODS: Subjects were
      exposed to 60 degrees peak-peak, pitch backwards from upright motion while
      viewing a video of the environment with 180 degrees phase delay. Motion duration
      was a maximum of 30 min and frequency was set to match individuals' spontaneous
      respiration. Conditions were: A, spontaneous breathing; B, inspiration cued to
      begin when head-down; C, inspiration cued to begin when upright; D, inspiration
      cued with a +/-18 degrees desynchronizing phase drift with respect to the tilt
      cycle. Nausea was rated and ventilation was recorded. RESULTS: Magnitudes of
      nausea ratings were ordered D<C<B<A (p=0.008) and speed at which nausea developed
      were ordered A<B<C<D (p=0.001). DISCUSSION: The lower sickness ratings and
      prolonged times to develop nausea in B, C, D confirm that controlled breathing
      gives some protection against motion sickness. The differences between B, C and D
      in the development of nausea support the hypothesis of Von Gierke and Parker [von
      Gierke HE, Parker DE. Differences in otolith and abdominal viscera graviceptor
      dynamics: implications for motion sickness and perceived body position. Aviat
      Space Environ Med. 65:747-51, 1994.] that motion sickness can be provoked by a
      conflicting mismatch between visceral and otolithic signals of orientation to the
      vertical. The mismatch is greatest in the more provocative condition B because
      the viscera are mechanically unloaded due to exhalation when the body attains
      uprightness whereas mismatch is lessened by the mechanical reinforcement afforded
      by inspiration in (C) and by inconstant relationships between visceral and
      otolithic signals in (D), both of which afford better protection against
      sickness.

PMID- 19592314
TI  - Isolation and purification of three flavonoid glycosides from the leaves of
      Nelumbo nucifera (Lotus) by high-speed counter-current chromatography.
AB  - Semi-preparative high-speed counter-current chromatography (HSCCC) was
      successfully used for isolation and purification of flavonoid glycosides from the
      leaves of Nelumbo nucifera (Lotus) by using a two-phase-solvent system composed
      of n-hexane-ethyl acetate-methanol-water (1:5:1:5, v/v/v/v). The targeted
      compounds isolated, collected and purified by HSCCC were analyzed by high
      performance liquid chromatography (HPLC). A total of 4.6 mg of isoquercitrin, 9.1
      mg of hyperoside and 3.0 mg of astragalin with the purity of 95.8%, 97.5% and
      98.3%, respectively, were obtained in one-step separation and less than 6 h from
      80 mg of crude extract from the leaves of N. nucifera. The chemical structures of
      all the three compounds were identified by MS, (1)H NMR, (13)C NMR. Astragalin
      was obtained from N. nucifera for the first time.

PMID- 19592313
TI  - Voltammetric study of gold-supported lipid membranes in the presence of
      perfluorooctanesulphonic acid.
AB  - The effect of perfluorooctanesulphonic acid (PFOS) on lipid membranes was studied
      using supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer as the
      model membrane. Phospholipid bilayer was deposited on gold electrode using a
      combination of the Langmuir-Blodgett and Langmuir-Schaefer (LB/LS) techniques.
      Electrodes were modified with two different types of membranes: DMPC bilayers
      initially containing PFOS and pure DMPC bilayers later exposed to the PFOS
      solutions. Such approach allowed studying both the changes in membrane
      characteristic imposed by the perfluorinated compound present in the model
      membrane and the process of its incorporation into the membrane. Studies with
      anticancer drug doxorubicin revealed that PFOS inhibits drug transport through
      the phospholipid bilayer and its effect can be compared to that of cholesterol.
      Moreover, the different trends observed in the changes in electron transfer rate
      constant (k(s)) calculated for ferricyanides and in peak current of
      hexaamineruthenium chloride showed that electrostatic interactions between
      electroactive probes and PFOS molecules incorporating into phospholipid bilayers
      play an important role and should be taken into account while explaining the
      interactions of perfluorooctanesulphonic acid with model biological membranes.

PMID- 19592315
TI  - Comparative performance of novel solutions for submucosal injection in porcine
      stomachs: An ex vivo study.
AB  - BACKGROUND: Submucosal injection of normal saline (NS) is commonly used during
      endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) but
      is quickly absorbed. Sodium hyaluronate (SH) produces longer lasting mucosal
      elevation but is expensive. AIMS: To evaluate the performance of novel solutions
      for submucosal injection in comparison with NS and SH. METHODS: One ml of the
      following solutions was injected in the submucosa of fresh specimens of porcine
      stomachs: NaCl 0.9%, SH 0.4%, human albumin 25%, two artificial tears solutions,
      namely, hydroxypropyl methylcellulose (HPMC) 0.3%/dextran 70.1% and polyvinyl
      alcohol (PVA) 1.4%, hydroxyethyl starch (HES) 6% and polyethylene glycol (PEG)
      50%. The time until the disappearance of the mucosal elevation was recorded in a
      blind manner. RESULTS: The median duration of mucosal elevation was significantly
      longer with HPMC/dextran, PVA, HES, PEG and SH (29, 26, 38, 31.5, and 41.5min,
      respectively) compared with NS (12min) (p<0.05 for each comparison). There were
      no significant time differences between SH and HPMC/dextran, HES and PEG
      (p>0.05). CONCLUSIONS: Novel viscous or hypertonic solutions for submucosal
      injection, perform better than normal saline and equally well as sodium
      hyaluronate in porcine stomachs in vitro.

PMID- 19592316
TI  - Rapid development of severe thrombocytopenia in a female with chronic hepatitis C
      after single-dose pegylated interferon therapy.

PMID- 19592317
TI  - Internalization of the thin ideal among low-income ethnic minority adolescent
      girls.
AB  - Internalization of the thin ideal has been thought to occur disproportionately
      among Caucasian, upper-class girls and women. The current research challenges
      this view by assessing thin-ideal internalization among low-income ethnic
      minority girls (N=48). This research identifies differences between low-income
      ethnic minority adolescent girls who highly internalize the thin ideal (HI) and
      those who have lower internalization of thinness (LI). Results indicate that HI
      and LI groups do not differ based on ethnicity or weight categorization. Body
      satisfaction, competence, and perceived sociocultural pressure were analyzed as
      individual differences between HI versus LI participants. Those in the LI group
      have higher athletic competence and body satisfaction ratings for weight compared
      to the HI group. By identifying differences in thin-ideal internalization in this
      understudied population, factors that may protect someone from endorsing the thin
      ideal may be discovered.

PMID- 19592318
TI  - Body image and body change strategies among adolescent males and females from
      Fiji, Tonga and Australia.
AB  - The current study was designed to investigate the body image and body change
      strategies of adolescents from Fiji, Tonga and Australia. Participants were 628
      Fijians, 463 Indo-Fijians, 598 Tongans and 535 European Australians. Adolescents
      completed measures of height, weight, body dissatisfaction, strategies to lose
      weight, increase weight and increase muscles. The results demonstrated that
      overweight adolescents were more dissatisfied with their bodies than those who
      were normal weight. Overweight Fijians and Tongans were more satisfied with their
      body than Indo-Fijian or Australian adolescents. Tongans, followed by Fijians and
      Indo-Fijians, were more likely to engage in strategies to lose weight, increase
      weight and increase muscles. These results are consistent with the focus in Fiji
      and Tonga on the value of the large body ideal, but may also reflect the recent
      focus on the attainment of a healthy body size.

PMID- 19592319
TI  - Malignant melanoma and pregnancy: second thoughts.
AB  - Malignant melanoma (MM) was considered a hormone-sensitive tumour, and pregnancy
      was thought to increase its risk and cause faster progression and earlier
      metastasis. Several controlled studies demonstrated similar survival rates
      between pregnant and non-pregnant patients and concluded that early reports of
      advanced MM of pregnancy were probably due to late diagnosis. We retrieved
      information from our database between 1997 and 2006 on all patients diagnosed as
      having MM during and up to 6 months after pregnancy (n=11) and compared them to
      age-matched, non-pregnant, MM patients (n=65, controls) treated by us during that
      period. The mean Breslow thickness was 4.28mm for the pregnant patients and
      1.69mm for the controls (p=0.15). The sentinel nodes were metastatic in five
      pregnant patients compared to four controls (p<0.0001). Two patients in the
      pregnancy group and one control died of MM (p=0.0532). Our results indicate a
      negative effect of pregnancy on the course of MM.

PMID- 19592320
TI  - Are blood pressure levels taken during a secondary care diabetic clinic likely to
      be higher than when measured in primary care?
AB  - Blood pressure management guidelines are widely available. Our aim was to examine
      differences in blood pressure on the same subjects in primary and secondary care.
      We identified 661 diabetic subjects with measurements with the aid of the SAIL
      databank. Blood pressure in primary care was significantly lower than secondary
      care.

PMID- 19592321
TI  - Associations between media use and health in US children.
AB  - OBJECTIVE: Television viewing has been associated with poorer health attributes,
      but relationships between computer use and health are less clear. The aim of this
      study was to determine associations between TV and computer use, both separately
      and combined, and health attributes in US children. METHODS: We performed
      bivariate and multivariate logistic regression analyses of cross-sectional data
      on 54 863 children ages 6 to 17 years who participated in the National Survey of
      Children's Health. Key independent variables were TV, computer, and combined
      media use; outcome variables were 6 measures of health. RESULTS: In models
      controlling for a wide range of sociodemographic variables, each additional hour
      of television viewing was associated with greater odds of overweight/obesity
      (odds ratio [OR] 1.05, 95% confidence interval (95% CI) 1.02-1.08), poorer oral
      health (OR 1.05, 95% CI 1.02-1.09), social-emotional problems (OR 1.08, 95% CI
      1.05-1.11), concern about self-esteem, and lower social competence. Greater
      computer use was associated only with overweight/obesity (OR 1.04, 95% CI 1.01
      1.07). Combined media use showed similar, but weaker, health associations to
      television viewing alone. Interaction analyses showed that TV viewing was
      associated with overweight/obesity only for white, not black or Hispanic,
      children. CONCLUSIONS: TV/video use is associated with a broader range of
      negative physical and social-emotional health attributes than computer use.
      Associations between media use and health are modest, but persistent at the
      population level. TV/video use reduction strategies may lead to improved physical
      and social-emotional population health. However, reductions in TV viewing may
      have little effect on overweight/obesity in black or Hispanic children.
      Mechanisms underlying observed health associations need further study.

PMID- 19592322
TI  - Electronic media use and adolescent health and well-being: cross-sectional
      community study.
AB  - OBJECTIVE: To describe time adolescents spend using electronic media (television,
      computer, video games, and telephone); and to examine associations between self
      reported health/well-being and daily time spent using electronic media overall
      and each type of electronic media. METHODS: Design-Cross-sectional data from the
      third (2005) wave of the Health of Young Victorians Study, an Australian school
      based population study. Outcome Measures-Global health, health-related quality of
      life (HRQoL; KIDSCREEN), health status (Pediatric Quality of Life Inventory 4.0;
      PedsQL), depression/anxiety (Kessler-10), and behavior problems (Strengths and
      Difficulties Questionnaire). Exposure Measures-Duration of electronic media use
      averaged over 1 to 4 days recalled with the Multimedia Activity Recall for
      Children and Adolescents (MARCA) computerized time-use diary. Analysis-Linear and
      logistic regression; adjusted for demographic variables and body mass index z
      score. RESULTS: A total of 925 adolescents (mean +/- standard deviation age,
      16.1+/-1.2 years) spent, on average, 3 hours 16 minutes per day using electronic
      media (television, 128 minutes per day; video games, 35; computers, 19;
      telephone, 13). High overall electronic media use was associated with poorer
      behavior, health status, and HRQoL. Associations with duration of specific media
      exposures were mixed; there was a favorable association between computer use
      (typing/Internet) and psychological distress, whereas high video game use was
      associated with poorer health status, HRQoL, global health, and
      depression/anxiety. Television and telephone durations were not associated with
      any outcome measure. CONCLUSIONS: Despite television's associations with obesity,
      time spent in other forms of media use appear more strongly related to adolescent
      health and well-being. This study supports efforts to reduce high video game use
      and further exploration of the role of computers in health enhancement.

PMID- 19592323
TI  - Rotational alignment of the distal femur: a literature review.
AB  - Rotational malalignment still accounts for an unacceptable number of failures in
      total knee arthroplasty (TKA). This paper presents a literature review of
      previously published papers describing rotational alignment of the distal femur
      and discussing different techniques in obtaining correct rotational alignment of
      the femoral component in TKA. Based on the published values, the following mean
      angular relationships between the rotation axes of the distal femur in the axial
      plane can be calculated: the posterior condylar line is on average 3 degrees
      internally rotated relative to the surgical transepicondylar axis (TEA), 5
      degrees relative to the anatomical TEA and 4 degrees relative to the
      perpendicular to the trochlear anteroposterior axis. The greatest interindividual
      variability is described for the trochlear AP axis. The worst track record
      regarding inter- and intraobserver variability is for the TEA. Given the large
      ranges and standard deviations of all reference axes, and the important inter-
      and intraobserver variability in the surgical location of the TEA, the use of a
      preoperative CT scan is recommended.

PMID- 19592324
TI  - The use of existing denture-satisfaction ratings for a diagnostic test to
      indicate prognosis with newly delivered complete dentures.
AB  - PURPOSE: The study investigated the relation between subjective satisfaction
      ratings of existing dentures and outcomes of newly delivered dentures, and the
      ability of the diagnostic test, using existing ratings, to indicate prognosis
      with newly delivered dentures. METHODS: Consecutive 165 edentulous patients were
      recruited from November 2001 to August 2006 at a university-affiliated hospital.
      Dentures were fabricated with an acrylic base with full-balanced occlusion using
      hard resin artificial teeth by multiple prosthodontists. At the baseline and 3
      month after delivery, patients rate their overall, maxillary, and mandibular
      satisfaction for existing and replaced dentures on a 100-mm visual analogue scale
      (VAS). The association between baseline ratings and newly delivered dentures was
      analyzed by regression analysis. The test's performance was measured by
      constructing a two-by-two table; patients with the following cutoff values on the
      VAS (overall: <or=31; maxillary: <or=47; mandibular: <or=36) were considered
      unsatisfied with existing or new dentures. Relative validity of the diagnostic
      tests was assessed by means of sensitivity, specificity, and likelihood ratios.
      RESULTS: Mandibular dentures showed a significant association between baseline
      and new dentures (coefficient=0.27, p=0.01). Results of test measures for
      overall, maxillary, and mandibular existing dentures were 71%, 38%, and 87%
      (sensitivity); 62%, 66%, and 49% (specificity); and 1.1, 1.9, and 1.7 (positive
      likelihood), and 0.5, 1.0, and 0.2 (negative likelihood). CONCLUSIONS: Test
      performance indicates that the negative (satisfied) result for mandibular
      existing dentures may be useful to rule out the unsatisfied patients with new
      mandibular dentures.

PMID- 19592325
TI  - Cutaneous polyarteritis nodosa in adult onset Still's disease.
AB  - Adult onset Still's disease (AOSD) is a well recognized clinical disorder
      characterized by a typical rash. However, there have been several atypical
      cutaneous findings reported in patients with AOSD. Cutaneous polyarteritis nodosa
      (PAN) is a necrotizing vasculitis of the small and medium sized arteries,
      distinguishing itself from systemic PAN by its restriction to the skin and to the
      neurological and osteo-muscular systems. We report the case of a patient with
      AOSD who is unique in having developed cutaneous polyarteritis nodosa (PAN)
      during the active phase of her disease. To the best of our knowledge, no previous
      cases of AOSD associated with a cutaneous variant of PAN have been reported.

PMID- 19592326
TI  - Measuring the impact of oral mucosa disease on quality of life.
AB  - Our objective was to study the quality of life in patients with oral mucosa
      disease. Two hundred sixteen consecutive patients with oral pathology were
      studied at the Department of Oral Medicine, University of Murcia (Spain). Sixty
      patients had burning mouth syndrome, 100 oral lichen planus, 41 recurrent
      aphthous stomatitis and 15 had and other oral mucosa disorders. The instruments
      applied were the Spanish version of the SF-36, used to evaluate general quality
      of life, and the OHIP-49, Spanish version, to measure oral health-related quality
      of life. With respect to oral quality of life (OHIP-49 all items), the worst
      scores were found for burning mouth syndrome. The group formed by other mucosal
      lesions presented the lowest scores for the domains role physical and general
      health in the SF-36. Oral mucosa diseases have a negative impact on health and
      quality of life. Administration of specific and generic questionnaires provides a
      detailed picture of the impact of oral diseases on patients, which adds
      information that may be useful in clinical practice.

PMID- 19592327
TI  - [Contribution to the qualification of hospital ethics bodies in the cancer
      centers].
AB  - The present op-ed article reports on a thesis study which examines the emergence
      of ethics committees in health care institutions. These committees have developed
      rapidly over the past few years in order to address ethical issues related to the
      management and care of patients. However, the question is raised of whether the
      ethics committees established in hospitals are an appropriate and effective
      response to the demands of the law (bill L. 6111-1), which states that
      institutions should implement ethical policies but does not provide any guidance
      on what should be done in practice.

PMID- 19592328
TI  - [The ethical implications of prospective payment and patient care].
AB  - With the introduction of the new prospective payment system considerable concern
      is being expressed that with the dominant emphasis on coasts, the principals of
      access and quality might be compromised. A new concept now emerged in care:
      productivity. How can we conjugate with the preset price for services to its
      beneficiaries based on average coasts of hospital care for patients' quality of
      care, patients and nursing team expectations and ethic? Which room will have
      ethic in that new way of redefining care? Will it be a risk that some patients
      may become "outliers"? Will the service take over the care?

PMID- 19592329
TI  - [What good? From benevolence to autonomy principles].
AB  - In medical practice, habits and ethics, on one hand, means, on the other hand,
      have evolved and induce the addition of autonomy to benevolence principle. In
      usual cases, traditional paternalism should be abandoned for allowing the patient
      to express his/her good and his/her choice for medical decision. This changes
      deeply doctor-patient relationship. Therefore, the physicians have to improve
      their practice in order to decrease inconveniences and increase advantages of
      this new relation, to finally better respect patients and their will.

PMID- 19592330
TI  - [Withholding and withdrawal decisions in oncology: legal frame and practice].
AB  - Whereas medicine is progressing in illness treatment that used to be incurable,
      physicians are still faced with treatment failure. Hippocrates used to say:
      "primum non nocere" [1]. When the patient cannot expect benefit from potentially
      aggressive care, current or possible treatments have to be challenged to leave
      just the ones giving immediate benefice. To determine a legal frame and to
      protect people in the end of life, law n degrees 2005-370 concerning to the
      rights of ill people and end of life was declaimed during April 2005. After
      presenting a clinical course illustrating a situation of difficult end of life,
      we propose an introduction point by point of the law, opposing practical
      situations to law and medical deontological code. Withholding and withdrawal
      decisions theme is taken by the standpoint of the doctor initiating this thought,
      the patient request, and the case of patient who cannot express his will.

PMID- 19592332
TI  - [JACIE: from guidelines to clinical practice and continuous quality improvement,
      the Leon-Berard cancer center experience].
AB  - JACIE, a European certification program for stem cell transplantation, has now
      been recognized by the French Health Authorities. It can be considered as an
      evaluation of professional practice, an activity that can be promoted by health
      centres. The present article has two aims: firstly, it describes the structure of
      the certification standard based on the relative structure of each of its
      components; secondly, it reports on the experience acquired by the Leon-Berard
      cancer centre (Lyon-France) during the certification of its own stem cell
      transplantation program. The JACIE manual written in English is divided into
      three parts corresponding to the three processes identified. Part B describes the
      clinical haematopoietic stem cell transplantation program. Part C is dedicated to
      the collection of haematopoietic stem cells from blood and marrow. Finally, part
      D applies to the cell therapy laboratory in charge of cell preservation and the
      preparation of grafts for re-infusion. After the application has been submitted
      to the JACIE board, a date is set for an inspection visit. The cell therapy
      laboratory at Leon-Berard cancer centre has already participated to a certified
      transplantation project of the Edouard-Herriot Hospital (Lyon public hospitals)
      [parts C and D of the certification]. The executive board proposed that the
      clinical haematology unit of the cancer centre also applied for JACIE
      certification. A multidisciplinary work group-combining document writing skills
      and a real capacity to convince and motivate clinical staff was formed. Secondly,
      a comprehensive collection of existing documents was issued and the clinical
      pathway of the patients was formalized so that no step of the graft process would
      be omitted. A physician from another hospital also tested the evaluation process
      with the organisation of a mock visit. He confirmed that everything was in good
      way and provided recommendations to improve the program. This huge preparation
      provided invaluable learning opportunities to the participants. After the final
      visit by JACIE inspectors, the cancer centre received four-year certification.
      The challenge is now to maintain this momentum for the next certifications and to
      better take into account the ethical and juridical constraints of haematopoietic
      stem cell transplantation.

PMID- 19592331
TI  - [A difficult diagnosis].
AB  - The patient information and obtaining their consent before any therapeutic
      constitute a basis for medicine exercise. However, there are situations where the
      physician may be in default. In that case, concepts of benefit/risk balance, of
      clear and appropriate information, and of legal liability for medico-surgical
      staff takes all their magnitude. That was the case in our observation, with a 69
      years old patient with history of smoking, presenting a suspicious lung opacity
      which will require, following an agreement by multidisciplinary meeting, an
      exploration by thoracotomy despite an acceptable but altered respiratory
      function, as a result of a post-smoking broncho-emphysema. The non-malignant
      character of the suspected lesion raise questions about the risks involved, the
      benefit/risk balance, and the legal risk scopes of the medicosurgical staff as
      defined in the Cancer programme framework.

PMID- 19592334
TI  - [The role of vitamin D in the development of cardiac failure].
AB  - Congestive heart failure is a chronic disease, whose incidence is especially
      growing in the subpopulation of elderly people. The majority of these patients
      have vitamin D levels in the insufficient range. Skin synthesis is the most
      important vitamin D source for humans. Congestive heart failure patients have
      relatively low outdoor activities. Consequently, a disease-related sedentary
      lifestyle is an important cause for the insufficient vitamin D status in
      patients. However, there is an accumulating body of evidence that vitamin D
      insufficiency plays a role in the etiology and pathogenesis of congestive heart
      failure. Vitamin D has direct effect on heart cells and indirect effect on the
      risk factors of the disease. Four major potential mechanisms may be important to
      explain the direct effects of vitamin D against congestive heart failure: the
      effect on myocardial contractile function, the regulation of natriuretic hormone
      secretion, the effect on extracellular matrix remodelling and the regulation of
      inflammation cytokines. It has been demonstrated that vitamin D has a high impact
      on congestive heart failure main risk factors as hypertension, renin-angiotensin
      system malfunction and atherosclerosis. In spite of the robust preclinical data
      only few clinical observations prove the positive effect of vitamin D on
      congestive heart failure.

PMID- 19592335
TI  - [PET/CT based radiotherapy treatment planning in head and neck cancers].
AB  - The purpose of this study was to evaluate the experiences of PET/CT based
      radiation planning in patients suffering from head and neck cancer. PET/CT based
      3D-conformal irradiation was used in eleven patients between March 2008 and
      February 2009. In six of the eleven cases the therapeutic plan was modified after
      PET/CT examination, as the previously determined lymph node negative state proved
      to be lymph node positive. For that reason, the treatment needed to be completed
      by chemotherapy and in some cases clinical target volume and planning target
      volume have been also modified. PET/CT examination has a decisive influence on
      therapeutic planning and on the planning process in patients with head and neck
      cancer.

PMID- 19592336
TI  - [Iodine content of mother's milk--Hungarian representative survey, 2006].
AB  - In Hungary, except for some small area, iodine content of soil, cultivated crops
      and potable water is low; therefore the iodine intake of Hungarian population is
      lower than the amount recommended by international organizations. The high iodine
      intake for pregnant and nursing women is important to ensure the appropriate
      iodine intake of fetus and nursing babies, as well. AIM: The objective of the
      study was to get a comprehensive picture of iodine content of mother's milk and
      to make recommendation for the level of iodine supplementation for pregnant and
      nursing women. METHODS: Following a country-wide sampling, iodine content of 72
      human milk samples were analyzed by inductively coupled plasma-mass spectrometry.
      RESULTS: Iodine intake in 42 percent of babies is lower than the recommended
      amount which could remarkably influence the physical and mental development of
      infants. CONCLUSIONS: Iodine supplementation and consumption of food with high
      iodine content is highly recommended during pregnancy and nursing.

PMID- 19592337
TI  - [Neuronal coding of spatial visual information].
AB  - The main differences between the geniculate and the ascending
      tectal/extrageniculate visual systems are the presence of multisensory units and
      the absence of the strict retinotopical organization in the tectal system. AIM:
      To investigate the coding of the visual and multisensory information in the
      tectal system, and to clarify the direction of visual information flow between
      the extrastriate cortex along the anterior ectosylvian sulcus and the lateral
      medialis-suprageniculate nucleus of the posterior thalamus. METHOD: Extracellular
      single-cell recordings were carried out in anesthetized, immobilized cats to
      visual and multisensory stimulation. RESULT: The thalamo-cortical route seems to
      have a dominant role in the bidirectional information flow between the LM-Sg and
      the AES cortex. The panoramic neurons in the AES cortex and the LM-Sg may code in
      their discharge rate the site of the spatial visual and multisensory information
      and exhibited multisensory cross-modal integration. CONCLUSION: Our results
      demonstrate the existence of a distributed population code of spatial
      multisensory information in the tectal visual system.

PMID- 19592338
TI  - [Adalimumab in arthritis psoriatica].

PMID- 19592340
TI  - [The Semmelweis-reflex].

PMID- 19592339
TI  - [Kalman Frank (1910-1999) -- remembering his life and work at the 10th
      anniversary of his death].

PMID- 19592341
TI  - [Extra-intestinal signs of Crohn disease].

PMID- 19592342
TI  - [To the Editors: Erno Balogh and Edith Potter].

PMID- 19592344
TI  - XII International Myeloma Workshop Abstract Book. February 26-March 1, 2009.
      Washington, DC, USA.

PMID- 19592343
TI  - [The importance of social pediatry knowledge in basic child health care--Academy
      of Parents in Gyor, Hungary].

PMID- 19592347
TI  - Adapting to students' social and health needs: suggested framework for building
      inclusive models of practice.
AB  - OBJECTIVE: This article builds on earlier discussions about college health
      research. The author suggests a 5-step framework that research practitioners can
      use to build models of practice that accurately address the needs of diverse
      campus populations. METHODS: The author provides 3 illustrations, drawn from
      published research examining college women with eating-related concerns, making
      the case for the importance of the Eating Disorders Not Otherwise Specified
      Diagnosis; examining African American students' social adjustment, making the
      case for an innovative model of needs; and examining minority sexual orientation
      students' identity development, making the case for a specialized developmental
      model. CONCLUSIONS: Following the illustrations, the author offers implications
      for practice and limitations of the proposed framework.

PMID- 19592348
TI  - Meningitis in a college student in Connecticut, 2007.
AB  - The authors describe a case of aseptic meningitis in a college student that was
      ultimately attributed to infection with lymphocytic choriomeningitis virus
      (LCMV). The authors also provide a review of LCMV infection, epidemiology, and
      public health implications. Providers should be aware of LCMV as a cause of
      meningitis in college students, especially those with a history of rodent
      exposure.

PMID- 19592349
TI  - Social capital in the college setting: the impact of participation in campus
      activities on drinking and alcohol-related harms.
AB  - OBJECTIVE: The authors aimed to replicate previous findings on social capital and
      harmful alcohol outcomes in the college setting and to ascertain the protective
      effects of additional indicators of social capital. METHODS: Over 4 years (2000
      2004), the authors conducted annual cross-sectional, random-sample student
      surveys at 32 US institutions of higher education (N = 15,875) and constructed
      multilevel models to examine the association between individual- and campus-level
      participation in campus activities and harmful drinking outcomes. RESULTS: At the
      individual level, community volunteerism was protective against harmful drinking
      outcomes. In contrast to past research, campus-level volunteerism was not
      significantly associated with the outcome measures. At both the individual and
      campus levels, participation in a religious organization was protective. Greek
      membership and varsity athletic participation were risk factors at the individual
      level. CONCLUSIONS: Results did not corroborate previous findings and revealed
      mixed results for other measures of participation at the campus level. The
      influence of social capital on college alcohol consumption deserves further
      attention.

PMID- 19592351
TI  - Development of a student engagement approach to alcohol prevention: the
      Pragmatics Project.
AB  - Significant involvement of students in the development and implementation of
      college alcohol prevention strategies is largely untested, despite
      recommendations by the National Institute of Alcohol Abuse and Alcoholism and
      others. OBJECTIVE: The purpose of the Pragmatics Project was to test a student
      engagement model for developing and implementing alcohol intervention strategies.
      PARTICIPANTS: The Pragmatics Project involved 89 undergraduate students on a
      large Midwestern university campus in the design and implementation of projects
      focused on reducing harm associated with high-risk drinking and off-campus
      parties. RESULTS: The engagement model used an innovative course piloted in the
      Human Development and Family Science department. The course successfully involved
      both students and the community in addressing local alcohol issues. CONCLUSIONS:
      The course design described would fit well into a Master of Public Health,
      Community Psychology, Health Psychology, or interdisciplinary curricula as well
      as the service learning model, and it is applicable in addressing other health
      risk behaviors.

PMID- 19592350
TI  - College student receptiveness to various alcohol treatment options.
AB  - OBJECTIVE: Heavy episodic drinking remains a significant problem on college
      campuses. Although most interventions for college students are behavioral,
      pharmacological treatments, such as naltrexone, could provide additional options.
      PARTICIPANTS: The authors evaluated receptivity to various alcohol treatment
      options in a general population of college student drinkers (N = 2,084), assessed
      in 2005. METHODS: The authors asked participants to indicate which of 8 treatment
      options (ie, self-help book, self-help computer program, self-help group, group
      therapy, individual therapy, monthly injection, targeted oral medication, or
      daily oral medication) they would be willing to consider if they were going to
      cut down on or stop drinking. RESULTS: Over 50% of drinkers expressed
      receptiveness to self-help options or psychotherapy options, and over 25% of
      drinkers expressed receptiveness to medication options. CONCLUSIONS: Increasing
      treatment options for students interested in reducing or stopping drinking by
      offering pharmacological interventions such as naltrexone could provide an
      important unmet need among college students.

PMID- 19592352
TI  - Gateway health behaviors in college students: investigating transfer and
      compensation effects.
AB  - OBJECTIVE: There is a dearth of studies on the mechanisms of multiple risk
      behaviors, even though these behaviors are significant public health issues. The
      authors investigated whether health behavior interventions have transfer or
      compensatory effects on other health behaviors. PARTICIPANTS AND METHODS: The
      authors looked at transfer and compensation effects of 3 health behaviors
      (smoking, alcohol use, and physical activity) in a sample of college students
      aged 18 to 25 years (N = 973; 84% born in the United States; 50% female; 25%
      Japanese, 19% Caucasian, 16% mixed). RESULTS: The study revealed the following
      evidence for transfer effects: (1) nonsmokers consume less alcohol, (2) regularly
      active people smoke less, and (3) nondrinkers smoke less. The authors also found
      the following compensation effects: (1) regularly active people consume alcohol
      more frequently; and (2) alcohol drinkers are more active. CONCLUSIONS:
      Interventions involving college students' smoking, alcohol use, and physical
      activity need to take into account both transfer and compensation considerations
      to maximize health impacts.

PMID- 19592353
TI  - Predicting physical activity of first-year university students: an application of
      the theory of planned behavior.
AB  - OBJECTIVE: The purpose of this study was to apply Ajzen's theory of planned
      behavior (TPB) and a measure of past physical activity behavior to predict first
      year students' physical activity intentions and behavior. PARTICIPANTS AND
      METHODS: First-year university students (N = 212) completed measures of TPB
      variables and past physical activity at the start of the 2006 fall semester and a
      measure of physical activity 8 weeks later. RESULTS: The TPB variables explained
      37% of the variance in intentions, increasing to 39% with the addition of past
      behavior. Logistic regression showed that past behavior predicted whether
      students met Health Canada standards for being physically active (4 > or
      =sessions of moderate/vigorous physical activity per week). CONCLUSIONS: Findings
      are consistent with other research showing that the TPB offers a good prediction
      of physical activity intentions but falls short of predicting behavior.

PMID- 19592354
TI  - Depressive symptoms, stress, and social support among dental students at a
      historically black college and university.
AB  - OBJECTIVE: The authors measured the prevalence of depressive symptoms among
      dental students at a historically black college in the United States to determine
      how depressive symptoms, stress, and social support influence each other within
      this student population. PARTICIPANTS: Dental students (n = 143) completed a self
      administered survey to assess depressive symptoms, stress, and social support,
      using validated and reliable instruments. Participants also reported demographic
      variables. METHODS: The authors used multivariable linear regression controlling
      for potential confounding. RESULTS: The prevalence of depressive symptoms was
      16.7%. There were significantly higher levels of stress for students with
      depressive symptoms compared with those without such symptoms (p < .01), and
      students with depressive symptoms had significantly lower levels of social
      support (p < .01). Results show higher levels of depressive symptomatology to be
      related to decreased social support at both high and low stress levels (p < .01).
      CONCLUSIONS: Stress and social support are associated with depressive symptoms
      among dental students.

PMID- 19592356
TI  - Associations between the five-factor model of personality and health behaviors
      among college students.
AB  - OBJECTIVE: In fall 2006, the authors examined associations between the five
      factor model of personality and several key health behaviors. METHODS: College
      students (N = 583) completed the American College Health Association-National
      College Health Assessment and the International Personality Item Pool Big Five
      short-form questionnaire. RESULTS: Highly conscientious individuals were more
      likely to wear seat belts, utilize alcohol-related harm reduction, exercise, get
      enough sleep, and consume fruits and vegetables. They were also less likely to
      smoke cigarettes, consume alcohol, and binge drink. Highly extraverted
      individuals were more likely to smoke cigarettes, consume alcohol, binge drink,
      and have multiple sexual partners, and they were less likely to engage in alcohol
      related harm reduction, use condoms, and get enough sleep. CONCLUSIONS: These
      findings are supportive of a growing body of evidence indicating that
      conscientiousness and extraversion are robust concomitants of health behaviors
      among college students.

PMID- 19592355
TI  - Rx for a party: a qualitative analysis of recreational pharmaceutical use in a
      collegiate setting.
AB  - OBJECTIVE: Using a qualitative methodology, the author examined the
      sociorecreational use of pharmaceuticals in a collegiate setting. PARTICIPANTS:
      In all, 91 college students from a public, 4-year institution for higher learning
      in the Southwest participated in this study. METHODS: The author conducted
      semistructured interviews between May 2004 and December 2005; they then audio
      recorded, transcribed, and examined the interviews for themes related to the
      sociorecreational use of prescription drugs. RESULTS: A variety of prescription
      drugs are used for a number of purposes, including to experience pleasure, manage
      the duration or intensity of another drug's effects, party or socialize with
      friends and peers in leisure settings, facilitate sociorecreational activities,
      and help structure free time. CONCLUSIONS: Pharmaceuticals appear to be well
      integrated into the recreational drug use practices of college students, and
      prescription drug misuse presents a significant prevention challenge.

PMID- 19592357
TI  - Spiritual well-being and suicidal ideation among college students.
AB  - OBJECTIVE: This study explored whether specific dimensions of spiritual well
      being (religious well-being and existential well-being) relate to reduced
      suicidal ideation, and whether associations persisted after controlling for
      religiosity and psychosocial variables associated with suicide. PARTICIPANTS:
      Participants were 457 college students who completed measures that assessed
      spiritual well-being, religiosity, hopelessness, depression, social support, and
      suicidal ideation. METHODS: The authors used linear regression modeling to assess
      religious and spiritual correlates of suicidal ideation. RESULTS: After
      controlling for demographic variables and psychosocial factors, neither
      involvement in organized religion nor religious well-being significantly
      contributed to suicidal ideation. However, even after controlling for significant
      correlates, existential well-being remained a significant predictor of suicidal
      ideation. CONCLUSIONS: This investigation highlighted existential well-being as
      an important factor associated with lower levels of suicidal ideation among
      college students. Findings from this study focusing on the association between
      spiritual well-being and suicidality may prove especially beneficial to suicide
      prevention efforts.

PMID- 19592360
TI  - Proprioception and motor control in Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder that leads to a
      progressive decline in motor function. Growing evidence indicates that PD
      patients also experience an array of sensory problems that negatively impact
      motor function. This is especially true for proprioceptive deficits, which
      profoundly degrade motor performance. This review specifically address the
      relation between proprioception and motor impairments in PD. It is structured
      around 4 themes: (a) It examines whether the sensitivity of kinaesthetic
      perception, which is based on proprioceptive inputs, is actually altered in PD.
      (b) It discusses whether failed processes of proprioceptive-motor integration are
      central to the motor problems in PD. (c) It presents recent findings focusing on
      the link between the proprioception and the balance problems in PD. And (d) it
      discusses the current state of knowledge of how levodopa medication and deep
      brain stimulation affect proprioceptive and motor function in PD. The authors
      conclude that a failure to evaluate and to map proprioceptive information onto
      voluntary and reflexive motor commands is an integral part of the observed motor
      symptoms in PD.

PMID- 19592361
TI  - Role of cognition and priming in interlimb generalization of adaptive control of
      gait stability.
AB  - The authors examined the impact of (a) awareness of impending slip and (b)
      priming (to accelerate learning) on interlimb transfer of acquired stability
      control. Among the participants, 12 of 24 young individuals were not informed of
      2 impending slips on the nontrained left-side (UNWARN), whereas the other 12 knew
      the exact timing and location of the 1st left slip (WARN) following 24 right-side
      slips, given to all participants while walking. Both groups reduced the backward
      loss of balance (BLOB) incidence from 100% on the first slip to 0% on 24th slip.
      The authors found significantly better transfer of the improved stability control
      in WARN than in UNWARN, resulting in a greater reduction in BLOB on the 1st left
      slip (55% vs. 92%, respectively). The priming was evident with no BLOB on the 2nd
      left slip versus 50% on the 2nd right slip. Thus, the interlimb generalization
      can be improved by cognition and evidenced in priming.

PMID- 19592362
TI  - The Golden Hour: care of the LBW infant during the first hour of life one unit's
      experience.
AB  - Care practices during the first hour of life, the Golden Hour, can have a
      significant impact on outcomes of low birth weight infants. Although the latest
      edition of the Neonatal Resuscitation Program added guidelines for preterm
      infants, additional care is often indicated. Complications that could potentially
      be impacted by care in the first hour of life include thermoregulation,
      intraventricular hemorrhage, chronic lung disease, and retinopathy of
      prematurity. Our unit has implemented and revised a Golden Hour evidence-based
      care process that includes the use of realistic videotaped simulations, followed
      by team debriefing sessions. Early results of the revised process show reductions
      in the targeted complications.

PMID- 19592363
TI  - Understanding the sequence of pulmonary injury in the extremely low birth weight,
      surfactant-deficient infant.
AB  - Human lung development begins around day 26 postconception and continues
      throughout early childhood. Many crucial events can affect this delicate tissue
      as it develops, leading to altered and abnormal growth and development of the
      lungs, thereby yielding a variety of morbidities and sometimes even mortality.
      Understanding the pathophysiology of lung injury in the extremely low birth
      weight neonate is essential when caring for these infants, especially during the
      first hours of life. This article provides bedside clinicians with foundational
      information related to acute lung injury and the sequence of events that can
      ultimately lead to neonatal chronic lung disease and bronchopulmonary dysplasia.

PMID- 19592367
TI  - Serum anion gap in metabolic acidosis.

PMID- 19592365
TI  - Discharge teaching in the NICU: are parents prepared? An integrative review of
      parents' perceptions.
AB  - BACKGROUND: At the end of their infant's NICU stay, parents are expected to
      assume full responsibility for their infant's care. It is important to look at
      discharge practices from the parents' points of view to see whether our
      strategies are effective. OBJECTIVES: Review the literature for studies that give
      insight into parents' perceptions of the discharge process in order to assist
      health care providers in evaluating the available research and to identify any
      gaps in the literature. METHOD: A literature search was performed to identify
      published studies that discuss parental perceptions related to their preparedness
      for their infant's discharge home from the NICU. RESULTS: Data from the parents'
      perspective were lacking. There are limitations in the data that are available.
      Parents are not prepared for discharge and have unanswered questions. Parental
      perceptions are different from health care professionals' perceptions.
      DISCUSSION: The studies that have been done need to be repeated in different
      centers, with greater sample sizes, and with subjects of different cultures,
      ethnicities, and socioeconomic status. There is a need for more research into
      parental perceptions of preparedness for their infant's discharge and ways to
      increase parental preparedness for discharge home from the NICU.

PMID- 19592364
TI  - Supporting mothers in recovery: parenting classes.
AB  - Drug addiction is a serious issue in today's society. Women are giving birth to
      infants who are born addicted to illicit drugs, and these mothers are not able to
      care for their infants safely and competently without training and support. This
      article examines the prevalence of the problem. It also discusses the possible
      impact of parenting skills classes, as part of recovery efforts, for women
      seeking recovery who have recently given birth. Several programs already in place
      in the U.S have shown positive results for these mothers and their infants.
      Infants exposed in utero to illicit drugs need to be given all of the resources
      society can provide in an effort to stop the intergenerational cycle of drug
      addiction.

PMID- 19592369
TI  - Treating the infant of a minor.

PMID- 19592370
TI  - Case study: trisomy 13, a palliative care case.

PMID- 19592372
TI  - Gently encouraging breastfeeding in the NICU.

PMID- 19592371
TI  - Evidence-based clinical guidelines.

PMID- 19592373
TI  - Psychiatric rehabilitation leadership.

PMID- 19592374
TI  - Case managers' expectations about employment for people with psychiatric
      disabilities.
AB  - BACKGROUND: The importance of employment in lives of people with psychiatric
      disabilities is well documented. Yet, the role of case managers in facilitating
      or inhibiting employment opportunities for consumers is only beginning to be
      understood. This study examined the psychometric properties of a newly developed
      self-report measure designed to assess case managers' employment-related
      expectations of consumers. METHODS: Psychometric properties of a 24-item self
      report measure, Expectations for the Employability of People with Serious Mental
      Illness (EESMI), were examined using a sample of 107 case managers. EESMI items
      tap individual and social systems factors related to employment for people with
      psychiatric disabilities. Construct validity was assessed by relationships
      between EESMI scores and scores on measures of general expectations and opinions
      of people with serious mental illness, case manager burnout, and social
      desirability. FINDINGS: EESMI consists of three empirically derived subscales
      with good internal consistency. Case managers' scores on EESMI correlated
      positively with scores on general expectations and opinions about people with
      mental illness scales and were generally unrelated to social desirability scores.
      EESMI scores were positively related to case managers' perceptions of the
      employability of consumers on their caseloads. CONCLUSIONS: EESMI is a
      psychometrically sound measure of mental health professionals' employment-related
      expectations of consumers. Reliable and valid assessment is basic to the study of
      mental health professionals' role in increasing employment opportunities for
      people with psychiatric disabilities. Study limitations and directions for future
      research are discussed.

PMID- 19592375
TI  - Passing for "normal": features that affect the community inclusion of people with
      mental illness.
AB  - OBJECTIVE: The purpose of this study was to investigate specific features that
      indicate to community members that a person has a mental illness and the
      emotional reactions elicited by these features, in hopes of understanding
      barriers to the community integration of people living with mental illnesses.
      METHOD: Participants were 15 community members who had considerable experience
      with people with mental illnesses but no extensive clinical training (e.g., store
      clerks, landlords, clergy). A mixed qualitative-quantitative design elicited 1)
      participants' subjective experience of interacting with people with mental
      illness and 2) participants' ratings of specified features of people with mental
      illness. RESULTS: Interpretive phenomenological analysis of qualitative
      interviews suggested that a person's mental illness was only apparent from afar
      if s/he was responding to internal stimuli or wearing bizarre or inappropriate
      clothing. The person's illness usually became apparent through interacting with
      the community member. Participants reported feeling kind benevolence towards
      people with mental illness and rated the likelihood of people with mental illness
      to be threatening or violent as very low. Overall, participants' ratings of
      features of people with mental illness corroborated qualitative themes.
      CONCLUSIONS: These data suggest that stigma is not elicited simply by the
      presence of a person with a mental illness, and that the presence of a mental
      illness in most cases only becomes apparent through social interaction. Also,
      these data support conclusions that personal experience with people with mental
      illness reduces fear and increases benevolence and that personal contact should
      be integral to community integration and anti-stigma campaigns.

PMID- 19592376
TI  - Professionals' perceptions of the obstacles to education for people using mental
      health services.
AB  - OBJECTIVE: This article focuses on the preliminary findings of a research project
      investigating the barriers to participation in education for persons using mental
      health services. METHODS: A questionnaire was administered to 380 care
      coordinators in community health teams in the Nottinghamshire Healthcare NHS
      Trust to elicit their views on three areas where possible obstacles may be
      encountered: physical and psychological barriers found at an individual level,
      and structural barriers at the service level. Seventy care coordinators,
      predominantly community psychiatric nurses, replied and reported the barriers
      they saw facing 140 service users, all of whom were diagnosed with a severe
      mental illness. RESULTS: Analysis of the physical and psychological obstacles
      indicated that fluctuating illness was the major barrier, with mobility the least
      problematic issue. The average number of substantial barriers faced by an
      individual was five. Lack of funding for courses was the biggest service-related
      obstacle, closely followed by lack of information and opportunities for
      education. Low expectations on the part of mental health practitioners were seen
      as the least important service-related issue. CONCLUSIONS: Recommendations for
      service development highlight the role of education in recovery from mental
      illness.

PMID- 19592377
TI  - Elicitation of cognitions related to HIV risk behaviors in persons with mental
      illnesses: implications for prevention.
AB  - OBJECTIVE: An important step in research using the Theory of Reasoned Action and
      Theory of Planned Behavior (TRA/TPB) is conducting an elicitation process to
      identify topic and population specific cognitions. This study explored HIV risk
      behaviors in persons with mental illnesses and introduces findings from focus
      groups conducted during the development phase of an HIV primary and secondary
      prevention intervention study. METHODS: Researchers held four focus groups with
      persons with mental illnesses focused on HIV risks and condom use. RESULTS:
      Participants discussed sexual side effects of psychotropic medications as a
      potential cause of both medication non-adherence and HIV risk behaviors. The
      intersection of these two issues is specific to this population. CONCLUSIONS: We
      conclude with the recommendation that HIV primary and secondary prevention
      intervention for persons with mental illnesses must incorporate the promotion of
      healthy sexuality, including attention to sexual side effects of psychotropic
      medications.

PMID- 19592378
TI  - Why and how people decide to stop taking prescribed psychiatric medication:
      exploring the subjective process of choice.
AB  - OBJECTIVE: Despite the piling evidence supporting the effectiveness of
      psychiatric medication, research has consistently shown that only about half of
      those administered treatment actually take it as prescribed. The purpose of the
      present study was to explore why and how people with a serious mental illness
      (SMI) choose to stop taking prescribed medication. METHOD: Seven persons with SMI
      who had been prescribed and had used medication in the past, but had not taken
      medication for at least a year, participated in semi-structured interviews, which
      were recorded and later transcribed. Qualitative analysis provided a foundation
      for sketching a hypothesized five-stage model of the process involved in choosing
      to stop medication. RESULTS: This study revealed the subjective experience of
      taking medication, dilemmas it evokes, and the struggle to develop a personal
      perspective, plan and choice with regard to medication use. CONCLUSIONS:
      Implications of these findings are discussed, emphasizing the importance of the
      "doctor-patient" relationship context.

PMID- 19592379
TI  - HIV and hepatitis C knowledge among individuals with serious mental illness.
AB  - OBJECTIVE: The present study examines knowledge of human immunodeficiency virus
      (HIV) and hepatitis C virus (HCV) among individuals with serious mental illness.
      METHODS: Two hundred and thirty-six people answered questions regarding their
      knowledge of HIV and HCV. RESULTS: The total correct score for the set of HIV
      items (79%) was significantly higher than the total correct score for the set of
      HCV items (70%). Although the majority of demographic variables were not
      significantly associated with knowledge, individuals who had been previously
      screened for HIV answered significantly more HIV and HCV questions accurately.
      CONCLUSIONS: These results indicate that there is a specific gap in knowledge
      about HCV among individuals with serious mental illness, suggesting the need for
      intervention development to increase disease-related knowledge.

PMID- 19592380
TI  - Enhancing systematic implementation of skills training modules for persons with
      schizophrenia: three steps forward and two steps back?
AB  - OBJECTIVE: This brief report addresses the systematic implementation of skills
      training modules for persons with schizophrenia or related disorders in three
      Dutch mental health agencies. METHODS: Information on barriers, strategies and
      integration into routine daily practice was gathered at 0, 12 and 24 months
      through interviews with managers, program leaders, trainers, practitioners and
      clients. RESULTS: Overall implementation of the skills training modules for 74%
      of the persons with schizophrenia or related disorders was not feasible.
      Implementation was impeded by an incapable program leader, organizational
      changes, disappointing referrals and loss of trainers. The agencies made
      important steps forward to integrate the modules into routine daily practice.
      CONCLUSIONS: A reach percentage of 74% in two years time is too ambitious and
      needs to be adjusted. Systematic integration of the modules into routine daily
      practice is feasible, but requires solid program management and continuous effort
      to involve clients and practitioners.

PMID- 19592381
TI  - Hybrid transitional-supported employment using social enterprise: a retrospective
      study.
AB  - OBJECTIVE: This brief report examines the implementation of a hybrid transitional
      supported employment program using a social enterprise model to improve work
      skills and work behavior of people with psychiatric disabilities. METHODS: The
      subjects of this study included 25 consumers enrolled in a social enterprise cafe
      training program between May 2006 and December 2007. Work behavior assessments
      and supported employment tenure were retrospectively analyzed. RESULTS: All
      training participants who completed the 20-month training program demonstrated
      significant improvement in work behavior before leaving the transitional training
      at the cafe. Individuals who completed the transitional training at the cafe went
      on to sustain competitive employment for an average of 44 weeks. CONCLUSION: The
      social enterprise model is deemed helpful in assisting people with psychiatric
      disabilities to improve their employment outcomes.

PMID- 19592382
TI  - Development and evaluation of a health promotion group for individuals with
      severe psychiatric disabilities.
AB  - OBJECTIVE: A six-step program development and evaluation method integrating
      recovery principles of empowerment and choice in healthcare decisions with theory
      driven research from the fields of health promotion and psychiatric
      rehabilitation is presented. METHODS: A pilot wellness program that taught basic
      nutrition, exercise, and stress management skills to individuals diagnosed with
      schizophrenia demonstrates how to complete each step. Pre-post pilot data are
      analyzed using paired-sample t tests. RESULTS: Nine people diagnosed with
      schizophrenia participated in the pilot program. Despite a small sample size and
      limited statistical power, a paired-sample t test suggested that the program
      appeared to increase participants' self-efficacy for health practices (p<.05),
      specifically in the domains of psychological well-being (p<.01) and health
      responsibility (p<.05), while decreasing their perceptions of the overall amount
      of stress in their life (p<.01). CONCLUSIONS: Treatment providers are encouraged
      to use the six-step method to create programs that successfully blend empirical
      research methodology with consumer-centered participation.

PMID- 19592383
TI  - The impetus of recovery.

PMID- 19592384
TI  - The need for evidence-based training strategies.

PMID- 19592386
TI  - Menopause, postmenopausal hormone use and risk of incident gout.
AB  - OBJECTIVE: To prospectively study the relation between menopause, postmenopausal
      hormone use and risk of gout, since female sex hormones have been postulated to
      decrease gout risk among women. METHODS: In the Nurses' Health Study, the
      association between menopause, age at menopause, postmenopausal hormone use and
      risk of self-reported physician-diagnosed incident gout among 92 535 women
      without gout at baseline was examined. Multivariate proportional hazards
      regression analysis was used to adjust for other risk factors for gout such as
      age, body mass index, diuretic use, hypertension, alcohol intake and dietary
      factors. RESULTS: During 16 years of follow-up (1 240 231 person-years), 1703
      incident gout cases were recorded. The incidence rate of gout increased from 0.6
      per 1000 person-years in women <45 years of age to 2.5 in women > or =75 years of
      age (p for trend <0.001). Compared with premenopausal women, postmenopausal women
      had a higher risk of incident gout (multivariate-adjusted relative risk
      (RR)=1.26; 95% confidence interval (CI) 1.03 to 1.55). Among women with a natural
      menopause, women with age at menopause <45 years had a RR of 1.62 (95% CI 1.12 to
      2.33) of gout compared with women with age at menopause 50-54 years.
      Postmenopausal hormone users had a reduced risk of gout (RR=0.82; 95% CI 0.70 to
      0.96). CONCLUSION: These prospective findings indicate that menopause increases
      the risk of gout, whereas postmenopausal hormone therapy modestly reduces gout
      risk.

PMID- 19592387
TI  - Obesity and cardiovascular thrombotic events in patients undergoing percutaneous
      coronary intervention with drug-eluting stents.
AB  - BACKGROUND: Previous studies have reported conflicting findings regarding the
      relation of body mass index (BMI) to outcomes following percutaneous coronary
      interventions (PCI). No study to date has directly examined the effect of obesity
      on cardiovascular thrombotic events after stent implantation. OBJECTIVE: To
      evaluate the effect of obesity on cardiovascular thrombotic events in patients
      undergoing PCI with drug-eluting stents. METHODS: We studied 4972 patients
      between January 2004 and December 2006. Patients were divided into three groups
      according to body mass index: normal (BMI <24.9 kg/m(2), n = 1284), overweight
      (BMI 25-29.9 kg/m(2), n = 2475) and obese (BMI > or =30 kg/m(2), n = 1213).
      Median follow-up was 26 (interquartile range 20-33) months. RESULTS: Composite
      cardiovascular thrombotic events, including cardiac death and non-fatal
      myocardial infarction, were significantly higher in obese patients (5.9%) than in
      normal (3.2%) and overweight (3.8%) patients (p = 0.001). The incidence of
      definite or probable stent thrombosis steadily increased with increasing body
      mass index (0.9% vs 1.0% vs 1.9% in normal, overweight and obese patients,
      respectively; p = 0.029). Multivariate analyses showed that obesity was an
      independent predictor of 3-year composite thrombotic events (hazard ratio 1.86;
      95% confidence interval 1.25 to 2.75; p = 0.003) and definite or probable stent
      thrombosis (2.17; 1.04 to 4.55; p = 0.040). CONCLUSIONS: Obese patients have a
      higher risk for long-term cardiovascular thrombotic events following PCI with
      drug-eluting stents than patients with normal weight.

PMID- 19592388
TI  - Randomised trial of three rapamycin-eluting stents with different coating
      strategies for the reduction of coronary restenosis: 2-year follow-up results.
AB  - BACKGROUND: Drug-eluting stent (DES) platforms devoid of durable polymer have
      potential to enhance long-term safety outcomes. The ISAR-TEST-3 study was a
      randomised trial comparing three rapamycin-eluting stents with different coating
      strategies. The present study examined 2-year outcomes of these patients and is
      the first large-scale trial to report longer-term outcomes with biodegradable
      polymer and polymer-free DES. METHODS: Patients with de novo coronary lesions in
      native vessels were randomly assigned to receive biodegradable polymer (BP; n =
      202), permanent polymer (PP; Cypher; n = 202) and polymer-free (PF; n = 201)
      stents. The 2-year endpoints of interest were target lesion revascularisation
      (TLR), death/myocardial infarction (MI), stent thrombosis and delayed
      angiographic late luminal loss (LLL) between 6-8 months and 2 years. RESULTS:
      There were no significant differences in TLR (8.4%, 10.4% and 13.4% for BP, PP
      and PF stents, respectively; p = 0.19), death/MI (5.9%, 6.4% and 6.5% with BP, PP
      and PF respectively; p = 0.97) or stent thrombosis (definite/probable 0.5%, 1.0%
      and 1.0% with BP, PP and PF, respectively; p = 0.82). Paired angiographic follow
      up at 6-8 months and 2 years was available for 302 patients (69.0% of eligible
      patients). Delayed LLL was significantly different across the treatment groups:
      0.17 (0.42) mm, 0.16 (0.41) mm and -0.01 (0.36) mm for BP, PP and PF stents,
      respectively (p<0.001). CONCLUSION: Clinical antirestenotic efficacy was
      maintained with all three platforms between 1 and 2 years, although angiographic
      surveillance showed ongoing delayed LLL with both BP and PP stent platforms. At 2
      years there was no signal of a differential safety profile between the three
      stent platforms.

PMID- 19592389
TI  - Development and validation of a clinical index to predict survival after cardiac
      resynchronisation therapy.
AB  - OBJECTIVE: To develop and validate a prognostic risk index of cardiovascular
      mortality after cardiac resynchronisation therapy (CRT). DESIGN: Prospective
      cohort study. SETTING: District general hospital. PATIENTS: 148 patients with
      heart failure (mean age 66.7 (SD 10.4) years), New York Heart Association class
      III or IV, LVEF <35%) who underwent CRT. INTERVENTIONS: CRT device implantation.
      MAIN OUTCOME MEASURES: Value of a composite index in predicting cardiovascular
      mortality, validated internally by bootstrapping. The predictive value of the
      index was compared to factors that are known to predict mortality in patients
      with heart failure. RESULTS: All patients underwent assessment of 16 prognostic
      risk factors, including cardiovascular magnetic resonance (CMR) measures of
      myocardial scarring (gadolinium-hyperenhancement) and dyssynchrony, before
      implantation. Clinical events were assessed after a median follow-up of 913
      (interquartile range 967) days. At follow-up, 37/148 (25%) of patients died from
      cardiovascular causes. In Cox proportional hazards analyses, (DSC) Dyssynchrony,
      posterolateral Scar location (both p<0.0001) and Creatinine (p = 0.0046) emerged
      as independent predictors of cardiovascular mortality. The DSC index, derived
      from these variables combined, emerged as a powerful predictor of cardiovascular
      mortality. Compared to patients with a DSC <3, cardiovascular mortality in
      patients in the intermediate DSC index (3-5; HR: 11.1 (95% confidence interval
      (CI) 3.00 to 41.1), p = 0.0003) and high DSC index (> or =5; HR: 30.5 (95% CI
      9.15 to 101.8), p<0.0001) were higher. Bootstrap validation confirmed excellent
      calibration and internal validity of the prediction model. CONCLUSION: The DSC
      index, derived from a standard CMR scan and plasma creatinine before
      implantation, is a powerful predictor of cardiovascular mortality after CRT.

PMID- 19592391
TI  - DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis.
AB  - BACKGROUND: Leucoencephalopathy with brain stem and spinal cord involvement and
      high brain lactate (LBSL) was first defined by characteristic magnetic resonance
      imaging and spectroscopic findings. The clinical features include childhood or
      juvenile onset slowly progressive ataxia, spasticity, and dorsal column
      dysfunction, occasionally accompanied by learning difficulties. Mutations in
      DARS2, encoding mitochondrial aspartyl-tRNA synthetase, were recently shown to
      cause LBSL. The signs and symptoms show some overlap with the most common
      leucoencephalopathy of young adults, multiple sclerosis (MS). OBJECTIVE: To
      clarify the molecular background of LBSL patients in Finland, and to look for
      DARS2 mutations in a group of MS patients. METHODS: Clinical evaluation of LBSL
      patients, DARS2 sequencing and haplotype analysis, and carrier frequency
      determination in Finland. RESULTS: All eight LBSL patients were compound
      heterozygotes for DARS2 mutations: all carried R76SfsX5 change, seven had
      M134_K165del, and one had C152F change. Axonal neuropathy was found in five of
      the eight patients. The carrier frequencies of the R76SfsX5 and M134_K165del
      mutations were 1:95 and 1:380, respectively. All patients shared common European
      haplotypes, suggestive of common European LBSL ancestors. No enrichment of the
      two common DARS2 mutations was found in 321 MS patients. CONCLUSION: All LBSL
      patients were compound heterozygotes, which suggests that DARS2 mutation
      homozygosity may be lethal or manifest as a different phenotype. The authors show
      here that despite identical mutations the clinical picture was quite variable in
      the patients. Axonal neuropathy was an important feature of LBSL. DARS2 mutations
      cause childhood-to-adolescence onset leucoencephalopathy, but they do not seem to
      be associated with MS.

PMID- 19592390
TI  - MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or
      mutation is responsible for severe mental retardation with stereotypic movements,
      epilepsy and/or cerebral malformations.
AB  - BACKGROUND: Over the last few years, array-comparative genomic hybridisation
      (CGH) has considerably improved our ability to detect cryptic unbalanced
      rearrangements in patients with syndromic mental retardation. METHOD: Molecular
      karyotyping of six patients with syndromic mental retardation was carried out
      using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions
      ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the
      following phenotypic similarities: severe mental retardation with absent speech,
      hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or
      cerebral malformations were also present in most of these patients. The minimal
      common deleted region of these 5q14 microdeletions encompassed only MEF2C, the
      gene for a protein known to act in brain as a neurogenesis effector, which
      regulates excitatory synapse number. In a patient with a similar phenotype, an
      MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together,
      these results strongly suggest that haploinsufficiency of MEF2C is responsible
      for severe mental retardation with stereotypic movements, seizures and/or
      cerebral malformations.

PMID- 19592392
TI  - Quantitative lung T cell responses aid the rapid diagnosis of pulmonary
      tuberculosis.
AB  - BACKGROUND: The diagnosis of smear-negative pulmonary tuberculosis (TB) is
      problematic. There are limited data on the profile of alveolar TB antigen
      specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB
      is unclear. METHODS: Antigen-specific interferon gamma (IFNgamma) responses to
      the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube),
      heparin-binding haemagglutinin and purified protein derivative were evaluated,
      using alveolar lavage cells, in 91 consecutively recruited South African patients
      suspected of having TB. RESULTS: Of 85 evaluable patients (29% HIV+), 24, 11, 48
      and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis,
      respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of
      all test results were inconclusive. Failure of the positive control was
      significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB
      (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin
      B, compared with phytohaemagglutinin, substantially reduced failure of the
      positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite
      and non-TB groups were used for outcome analysis, the percentage sensitivity,
      specificity, positive predictive value and negative predictive value for T
      SPOT.TB (> or = 20 spots/million alveolar mononuclear cells) and QuantiFERON-TB
      Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69%
      (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T
      SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB
      cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative
      alveolar lymphocyte IFNgamma responses had poor performance outcomes. CONCLUSION:
      Provided evaluable results are obtained, the RD-1, but not the heparin-binding
      haemagglutinin or purified protein derivative, alveolar lymphocyte IFNgamma
      ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test
      utility in high-burden settings may be limited by the high proportion of
      inconclusive results.

PMID- 19592394
TI  - Prediction of protein beta-residue contacts by Markov logic networks with
      grounding-specific weights.
AB  - MOTIVATION: Accurate prediction of contacts between beta-strand residues can
      significantly contribute towards ab initio prediction of the 3D structure of many
      proteins. Contacts in the same protein are highly interdependent. Therefore,
      significant improvements can be expected by applying statistical relational
      learners that overcome the usual machine learning assumption that examples are
      independent and identically distributed. Furthermore, the dependencies among beta
      residue contacts are subject to strong regularities, many of which are known a
      priori. In this article, we take advantage of Markov logic, a statistical
      relational learning framework that is able to capture dependencies between
      contacts, and constrain the solution according to domain knowledge expressed by
      means of weighted rules in a logical language. RESULTS: We introduce a novel
      hybrid architecture based on neural and Markov logic networks with grounding
      specific weights. On a non-redundant dataset, our method achieves 44.9% F(1)
      measure, with 47.3% precision and 42.7% recall, which is significantly better (P
      < 0.01) than previously reported performance obtained by 2D recursive neural
      networks. Our approach also significantly improves the number of chains for which
      beta-strands are nearly perfectly paired (36% of the chains are predicted with
      F(1) >or= 70% on coarse map). It also outperforms more general contact predictors
      on recent CASP 2008 targets.

PMID- 19592393
TI  - TileProbe: modeling tiling array probe effects using publicly available data.
AB  - MOTIVATION: Individual probes on an Affymetrix tiling array usually behave
      differently. Modeling and removing these probe effects are critical for detecting
      signals from the array data. Current data processing techniques either require
      control samples or use probe sequences to model probe-specific variability, such
      as with MAT. Although the MAT approach can be applied without control samples,
      residual probe effects continue to distort the true biological signals. RESULTS:
      We propose TileProbe, a new technique that builds upon the MAT algorithm by
      incorporating publicly available data sets to remove tiling array probe effects.
      By using a large number of these readily available arrays, TileProbe robustly
      models the residual probe effects that MAT model cannot explain. When applied to
      analyzing ChIP-chip data, TileProbe performs consistently better than MAT across
      a variety of analytical conditions. This shows that TileProbe resolves the issue
      of probe-specific effects more completely. AVAILABILITY:
      http://www.biostat.jhsph.edu/ approximately
      hji/cisgenome/index_files/tileprobe.htm.

PMID- 19592395
TI  - aGEM: an integrative system for analyzing spatial-temporal gene-expression
      information.
AB  - MOTIVATION: The work presented here describes the 'anatomical Gene-Expression
      Mapping (aGEM)' Platform, a development conceived to integrate phenotypic
      information with the spatial and temporal distributions of genes expressed in the
      mouse. The aGEM Platform has been built by extending the Distributed Annotation
      System (DAS) protocol, which was originally designed to share genome annotations
      over the WWW. DAS is a client-server system in which a single client integrates
      information from multiple distributed servers. RESULTS: The aGEM Platform
      provides information to answer three main questions. (i) Which genes are
      expressed in a given mouse anatomical component? (ii) In which mouse anatomical
      structures are a given gene or set of genes expressed? And (iii) is there any
      correlation among these findings? Currently, this Platform includes several well
      known mouse resources (EMAGE, GXD and GENSAT), hosting gene-expression data
      mostly obtained from in situ techniques together with a broad set of image
      derived annotations. AVAILABILITY: The Platform is optimized for Firefox 3.0 and
      it is accessed through a friendly and intuitive display: http://agem.cnb.csic.es

PMID- 19592396
TI  - Case report: Spontaneous regression of a supraclavicular thoracic duct cyst: case
      report with a follow-up of 25 years.
AB  - This article is a follow-up of a previously reported case of a thoracic duct
      cyst. In 1982, a left supraclavicular swelling appeared spontaneously in a 55
      year-old man. The mass was located near the lower part of the sternocleidomastoid
      muscle. Fine-needle puncture yielded chylous fluid. Radiography of the thoracic
      duct following direct puncture and injection of contrast medium revealed cystic
      dilatation of the upper part in close proximity to the jugular and subclavicular
      veins, with widening of the adjacent intrathoracic duct. Surgery was considered
      but was not performed as the patient had no symptoms. Radiological re-examination
      in 1991 showed progression in the size of the cystic expansion but, as the
      patient was still without complaints, no treatment was given. In 1995 (after 13
      years), the patient noted that the cyst had diminished spontaneously. Follow-up
      MR and clinical examination in 2007, 25 years after the first appearance, showed
      complete regression of both the cervical cystic dilatation and the widened
      intrathoracic duct. Thus, spontaneous regression of a cystic dilatation of the
      thoracic duct can occur.

PMID- 19592397
TI  - Case report: A rare cause of miliary nodules -- allergic bronchopulmonary
      aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a complex immune
      hypersensitivity reaction to the fungus Aspergillus fumigatus, which occurs in
      patients with asthma and cystic fibrosis. The common radiological findings
      include fleeting pulmonary opacities, bronchiectasis and mucoid impaction.
      Uncommon radiological findings encountered in ABPA include lung masses, perihilar
      opacities simulating hilar adenopathy and pleural effusions. Herein, we describe
      a 36-year-old man who presented to the chest clinic with miliary nodules on a
      chest radiograph and was diagnosed as having ABPA confirmed on both serology and
      lung biopsy. This is the first report of ABPA presenting as randomly scattered
      nodules on CT.

PMID- 19592398
TI  - Case report: Rapidly progressive metastatic pulmonary calcification: evolution of
      changes on CT.
AB  - Metastatic pulmonary calcification occurs in association with several disease
      processes and has a highly variable prognosis. In certain patients, it may prove
      fatal, and therefore prompt recognition of radiological signs is helpful for
      optimising patient management. We describe the progressive changes seen on CT in
      a 59-year-old man who had undergone renal transplant and subsequently developed
      metastatic pulmonary calcification. The merits of the different imaging
      techniques available and possible treatment options are reviewed.

PMID- 19592399
TI  - Case report: Liposarcoma of the sinonasal tract.
AB  - Nasal and paranasal malignant tumours account for less than 5% of all head and
      neck malignancies. Epithelial malignancies overwhelmingly predominate, with
      squamous cell carcinomas representing the most frequent histological subtype in
      this location. Soft-tissue sarcomas of the nasal cavity and paranasal sinuses are
      exceedingly rare. Here, we report two cases of myxoid liposarcomas that occurred
      in the nasal and paranasal regions, both of which presented diagnostic challenges
      and could not be diagnosed definitively from intraoperative frozen sections.
      These cases reinforce the notion that, while they are uncommon, sarcomas in
      general and liposarcomas in particular should still be considered as part of the
      differential diagnosis in patients presenting with obstructive symptoms in the
      nasal and paranasal sinuses.

PMID- 19592400
TI  - Case report: Hydropic leiomyoma of the uterus presenting in pregnancy: imaging
      features.
AB  - Uterine leiomyomas commonly undergo degenerative change, which can lead to
      variable imaging features. Diffuse hydropic change is an unusual form of
      degeneration that presents a considerable diagnostic challenge to both
      radiologists and pathologists, as it can mimic a malignant neoplasm on imaging
      and at histological analysis. We present the case of a giant diffuse hydropic
      leiomyoma presenting in the first trimester of pregnancy in a 36-year-old woman,
      the imaging features of which were suggestive of a more aggressive neoplasm. The
      sonographic and MRI appearances of the lesion are discussed, and the varied
      imaging features of leiomyomas are reviewed.

PMID- 19592402
TI  - Rasmussen's aneurysm -- undue importance to an uncommon entity?

PMID- 19592401
TI  - Case report: Imaging features of perianal leiomyoma.
AB  - A leiomyoma is a benign mesenchymal neoplasm that usually develops where smooth
      muscle is present. In this report, we present a rare case of perianal leiomyoma.
      The external anal sphincter was stretched over the surface of the leiomyoma and
      the internal anal sphincter was intact on surgery. It was confirmed as a deep
      soft-tissue leiomyoma on pathology. We describe the ultrasonographic and MRI
      findings of a rare case of perianal leiomyoma, together with differential
      diagnoses.

PMID- 19592403
TI  - Case of the month: An African woman presenting with acalculous cholecystitis and
      sclerosing cholangiopathy.

PMID- 19592404
TI  - Should antihistamines be used to treat anaphylaxis?

PMID- 19592405
TI  - Is systolic blood pressure all that matters? Yes.

PMID- 19592406
TI  - Is systolic blood pressure all that matters? No.

PMID- 19592407
TI  - US National Institutes of Health issue guidelines on stem cell.

PMID- 19592408
TI  - Perioperative use of dexmedetomidine in an infant with familial dysautonomia.
AB  - We present a case of a 10-month-old girl with familial dysautonomia, who was
      scheduled for the insertion of a gastrotomy tube via laparoscopy under general
      anaesthesia. We used a total i.v. anaesthetic technique including dexmedetomidine
      and titrated the drug to patients' haemodynamic status and BIS value. Vital signs
      remained virtually unchanged during the entire procedure, and the tracheal tube
      was removed at the end of the procedure. Postoperative course was uneventful.
      Careful planning of the anaesthetic management, understanding the physiological
      consequences, and being able to titrate the medications utilized are key to the
      decrease of complications encountered in these patients. We report the safe use
      of dexmedetomidine in an infant with this extremely rare condition.

PMID- 19592409
TI  - Radiofrequency catheter ablation of left ventricular outflow tract tachycardia
      with the assistance of the CartoSound system.
AB  - Catheter ablation of left ventricular outflow tract tachycardia (LVOTT) holds the
      risk of complications, if foci are located close to the coronary artery orifices.
      The use of an accurate three-dimensional electro-anatomic approach is necessary
      to avoid ablation in the coronaries. We report a case in which we demonstrate the
      value of the CartoSound system, in the ablation of LVOTT.

PMID- 19592410
TI  - A broad complex tachycardia with conflicting information from pacing manoeuvres.
AB  - A patient with a biventricular implantable cardioverter defibrillator for heart
      failure had a recurrent broad complex tachycardia and underwent
      electrophysiologic testing. The tachycardia was induced only with ventricular
      pacing. There was a 1:1 atrioventricular relationship with simultaneous atrial
      and ventricular activation. However, atrial pacing during tachycardia suggested
      atrial dissociation from the circuit. The findings, potential mechanisms, and
      treatment are discussed.

PMID- 19592411
TI  - 'And the beat goes on.' The cardiac conduction system: the wiring system of the
      heart.
AB  - The cardiac conduction system (CCS), consisting of the sino-atrial node,
      atrioventricular node and His-Purkinje system, is responsible for the initiation
      and co-ordination of the heart beat. In the last decade, our understanding of the
      CCS has been transformed. Immunohistochemistry, used in conjunction with
      anatomical techniques, has transformed our understanding of its anatomy;
      arguably, we now understand the position of the sino-atrial node (not the same as
      in medical textbooks), and our new understanding of the atrioventricular node
      anatomy means that we can compute its physiological and pathophysiological
      behaviour. Ion channel expression in the CCS has been shown to be fundamentally
      different from that in the working myocardium. Dysfunction of the CCS has
      previously been attributed to fibrosis, but it is now clear that remodelling of
      ion channels plays an important role in dysfunction during ageing, heart failure
      and atrial fibrillation. Differences in ion channel expression may even be
      responsible for the bradycardia in the athlete and differences in heart rate
      among different species (such as humans and mice). Recent work has highlighted
      less well-known components of the CCS, including tricuspid, mitral and aortic
      rings and even a third (retro-aortic) node. These additional tissues do not
      participate in the initiation and co-ordination of the heart beat and instead
      they are likely to be the source of various life-threatening arrhythmias. During
      embryological development, all parts of the CCS have been shown to develop from
      the primary myocardium of the linear heart tube, partly under the influence of
      the transcription factor, Tbx3.

PMID- 19592412
TI  - Glucose ingestion during endurance training in men attenuates expression of
      myokine receptor.
AB  - Glucose ingestion during exercise attenuates the release of the myokine
      interleukin-6 (IL-6) from working skeletal muscle, which results in a diminished
      increase in plasma IL-6. Interleukin-6 receptor alpha (IL-6Ralpha) expression in
      skeletal muscle is induced by acute exercise, mediated in part by an increased IL
      6 concentration in the bloodstream. We hypothesized that endurance training would
      increase the density of IL-6Ralpha in skeletal muscle and that glucose ingestion
      would attenuate the effect. Nine subjects performed 10 weeks of one-legged knee
      extensor training. They trained one leg (Glc-leg) while ingesting a glucose
      solution (Glc) and ingested a placebo (Plc) while training the other leg (Plc
      leg). Endurance training increased peak power by 14% and reduced the exercise
      induced gene expression of IL-6 and IL-6Ralpha in skeletal muscle and IL-6 plasma
      concentration. The IL-6Ralpha density increased to a lesser extent in the Glc
      leg, suggesting that glucose ingestion attenuates the effect of training on IL
      6Ralpha by blunting the IL-6 response. We conclude that glucose ingestion during
      endurance training attenuates the increase in IL-6Ralpha density.

PMID- 19592413
TI  - A simple automated stimulator of mechanically induced arrhythmias in the isolated
      rat heart.
AB  - Transient stretching of the ventricle can trigger arrhythmias and evoke
      ventricular fibrillation, especially when the stimulation occurs in the
      vulnerable period. To explore the sensitivity of small hearts we used a
      commercial pressure servo to study the kinetic relationship of left ventricular
      pressure to excitability and arrhythmias in the rat heart. Stimulation protocols
      were readily composed on the computer and programmed to vary the stimulus
      amplitude and timing relative to pacing. The pressure-induced premature
      ventricular excitations were similar to those observed in larger hearts, but the
      convenience of using small hearts allows the use of inexpensive transgenic
      animals to explore the molecular basis of transduction.

PMID- 19592414
TI  - Patient satisfaction with access in two interprofessional academic family
      medicine clinics.
AB  - BACKGROUND: Satisfaction with access to primary care is one component of overall
      patient satisfaction. The objectives of this paper were to describe patient
      satisfaction with access in interprofessional family practices and to examine
      predictors of being less than satisfied with access. METHODS: A survey was mailed
      to 770 randomly selected patients in two academic interprofessional family
      practices in Hamilton, Canada. Most items were positively worded statements on a
      five-point scale from strongly agree to strongly disagree. Outcomes were the
      proportion of respondents agreeing with statements regarding access. For items
      where > or =25% of respondents did not agree, we examined socio-demographic
      predictors of disagreement using multiple variable logistic regression. RESULTS:
      The response rate was 49.9% (384/770). One-quarter or more of respondents did not
      agree that they received an explanation if the appointment was delayed at the
      office, obtain urgent appointments, obtain prescription refills without a visit
      or that wait times at the office were reasonable. Predictors of not agreeing
      included younger age, being married or single, more educated, employed and of non
      white ethnicity. Less than 10 minutes was the most satisfactory wait time for the
      appointment to begin; however, the most common wait time reported was 11-20
      minutes. One-quarter of respondents had visited the weekend/holiday clinic in the
      past 12 months; however, use was not associated with perceived ability to obtain
      an appointment in 1-2 days. CONCLUSIONS: While satisfaction was generally high,
      some aspects of access could be improved by changes in practice organization or
      patient education regarding expectations.

PMID- 19592415
TI  - Successful administration of alteplase in a venous thromboembolism crossing
      through a patent foramen ovale.
AB  - We describe a case report observed via an echocardiography of a venous
      thromboembolism (VTE) that crosses through the patent foramen ovale to the left
      atrium and is successfully treated with alteplase. This is a case report of a
      tertiary care hospital without cardiac surgery facilities. An 81-year-old female
      seeking medical attention for dyspnoea, arriving at hospital with hypoxaemia,
      hypotension and prerenal failure. A computed tomographic (CT) pulmonary
      angiography was carried out, revealing a VTE. A transesophageal echocardiography
      (TEE) was carried out, exposing emboli in the right cavities, said thrombus
      crossing through the patent foramen ovale to the left atrium. A systemic
      thrombolysis is carried out using alteplase which improves the patient's
      condition and results in the disappearance of thrombotic images in the various
      cardiac cavities. The evolution is positive and there is no evidence of embolic
      or haemorrhagic complications. When a paradoxical embolism is present, in the
      context of a serious VTE, carrying out thrombolysis could be a therapeutic
      option.

PMID- 19592416
TI  - Restoration of atrial contractility after surgical cryoablation: clinical,
      electrical and mechanical results.
AB  - To assess the electrical sinus rhythm (SR) recovery and the mechanical
      effectiveness of the atrial contraction by echocardiography is essential in
      patients undergoing atrial fibrillation (AF) surgery. Between September 2006 and
      May 2008, patients with chronic AF (n=33; permanent=23 or paroxysmal=10)
      underwent mitral surgery and surgical cryoablation for AF. Exclusion criteria
      were: AF that has persisted for 10 years and left atrium (LA) >65 mm.
      Echocardiography study was performed at six months after surgery. Mean age was 62
      years (22 female, 11 male). Mean AF duration was three years (range 0.5-7.4).
      Mean atria size was 52.4+/-5.6 mm. Mitral valve surgery involved 32 prosthetic
      replacements and one mitral valve repair. There was no surgical mortality.
      Success rate for SR at three and six months was 90% and 82%, respectively. The
      only predictor of conversion to SR at six months was being at SR when discharge
      from the hospital. In patients in SR, echocardiographic study provided mechanical
      effectiveness of the atria in 100% of right atrium and 70% of the LA.
      Cryoablation for AF is an effective technique to recover electrocardiographic SR
      while being able to recover atrial contraction effectiveness.

PMID- 19592417
TI  - Surgical repair of multiple unruptured aneurysms of sinus of Valsalva.
AB  - Unruptured aneurysm of sinus of Valsalva (ASV) is a rare congenital anomaly. We
      describe a case of multiple unruptured ASV involving right and left aortic
      sinuses causing congestive cardiac failure in a 16-year-old boy who underwent
      successful surgical repair.

PMID- 19592418
TI  - Septic shock secondary to infection of a left ventricular thrombus.
AB  - We report the case of a 45-year-old woman who developed severe shock with
      multiorgan failure requiring admission to intensive care. Endomyocardial biopsy
      was performed and she was diagnosed with sepsis secondary to left ventricular
      thrombus abscess. Surgery was contraindicated and the patient received
      exclusively medical treatment; the clinical course was satisfactory and the
      patient is alive one year later. An apical thrombus may rarely be complicated by
      infection. Although management normally requires surgical excision, medical
      management may be effective in situations in which surgery is contraindicated.

PMID- 19592419
TI  - Intra-diaphragmatic pacemaker implantation in very low weight premature neonate.
AB  - Implantation of a pacemaker (PM) in very low weight premature neonates can be a
      challenging procedure because of the actual dimension of generators. Ideal
      placement of the PM is still controversial. We describe a technique of intra
      diaphragmatic PM implantation in a 1.3 kg neonate.

PMID- 19592420
TI  - CCR1 expression and signal transduction by murine BMMC results in secretion of
      TNF-alpha, TGFbeta-1 and IL-6.
AB  - Chemokine receptors (CCRs) are important co-stimulatory molecules found on many
      blood cells and associated with various diseases. The expression and function of
      CCRs on mast cells has been quite controversial. In this study, we report for the
      first time that murine bone marrow-derived mast cells (BMMC) express messenger
      RNA and protein for CCR1. BMMC cultured in the presence of murine recombinant
      stem cell factor and murine IL-3 expressed CCR1 after 5-6 weeks. We also report
      for the first time that mBMMC(CCR1+) cells endogenously express neurokinin
      receptor-1 and intercellular adhesion molecule-1. To examine the activity of CCR1
      on these BMMC, we simultaneously stimulated two receptors: CCR1 by its ligand
      macrophage inflammatory protein-1alpha and the IgE receptor FcepsilonRI by
      antigen cross-linking. We found that co-stimulation enhanced BMMC degranulation
      compared with FcepsilonRI stimulation alone, as assessed by beta-hexosaminidase
      activity (85 versus 54%, P < 0.0001) and Ca(2+) influx (223 versus 183 nM, P <
      0.05). We also observed significant increases in mast cell secretion of key
      growth factors, cytokines and chemokine mediators upon CCR1-FcepsilonRI co
      stimulation. These factors include transforming growth factor beta-1, tumor
      necrosis factor-alpha and the cytokine IL-6. Taken together, our data indicate
      that CCR1 plays a key role in BMMC function. These findings contribute to our
      understanding of mechanisms for immune cell trafficking during inflammation.

PMID- 19592421
TI  - A novel immunoregulatory protein in human colostrum, syntenin-1, for promoting
      the development of IgA-producing cells from cord blood B cells.
AB  - Human colostrum contains many bioactive factors that must promote the development
      of intestinal mucosal immunity in infants. Especially, the presence of certain
      cytokines such as transforming growth factor (TGF)-beta or IL-10 has been of
      great interest for IgA production as a function of mucosal immune response. In
      the present study, we attempted to investigate whether unidentified factors
      inducing generation of IgA-producing cells from naive B cells might exist in
      colostrum. For this purpose, colostrum samples were directly added to a culture
      consisting of naive B cells and dendritic cells from cord blood and CD40 ligand
      transfected L cells, comparing with recombinant IL-10 (rIL-10) and/or rTGF-beta.
      It was noted that most colostrum samples alone were able to induce IgA-secreting
      cells at higher levels than rIL-10 and/or rTGF-beta. IgA-inducing activity of
      colostrum was abolished by neither anti-neutralizing mAbs against IL-10 nor TGF
      beta, though partially by anti-IL-6 mAb. We prepared partially purified fractions
      from both pooled colostrums with and without IgA-inducing activity and
      comparatively performed quantitative proteomic analysis by two-dimensional
      difference gel electrophoresis followed by liquid chromatography-mass
      spectrometry. As a result, syntenin-1 was identified as a candidate for IgA
      inducing protein in colostrum. Western blot analysis indicated that levels of
      syntenin-1 in colostrum samples were correlated with their IgA-inducing
      activities. Moreover, we demonstrated that recombinant syntenin-1 could induce
      preferentially IgA production from naive B cells. These results suggest that
      syntenin-1 serves as one of IgA-inducing factors for B cells.

PMID- 19592422
TI  - Are neighbourhood social fragmentation and suicide associated in New Zealand? A
      national multilevel cohort study.
AB  - BACKGROUND: Studies of the association between neighbourhood fragmentation and
      suicide have yielded varied results, and none has simultaneously adjusted for
      neighbourhood fragmentation, neighbourhood deprivation and individual-level
      factors. METHOD: A multilevel analysis of a 3-year cohort study was carried out
      using probabilistic linkage of census and mortality records, and two measures of
      neighbourhood fragmentation. A total of 2.8 million respondents to the 1996 New
      Zealand census were followed up for 3 years for mortality (1101 suicide deaths in
      the analysis), aged from 20 to 74 years at follow-up. RESULTS: No consistent
      association was observed between either measure of neighbourhood social
      fragmentation and suicide, after controlling for individual-level confounders and
      neighbourhood deprivation. There was some evidence of a U-shaped relationship
      between neighbourhood fragmentation and suicide, especially for the Congdon(NZ)
      index. There was no evidence of an association for a nine-variable index that
      captured family-type variables as well as the usual attachment-type variables.
      Neighbourhood deprivation remained as an important predictor of suicide rates.
      CONCLUSION: This paper highlights the importance of understanding both the
      measure and the wider national context when considering neighbourhood effects on
      suicide.

PMID- 19592423
TI  - A fast and efficient translational control system for conditional expression of
      yeast genes.
AB  - A new artificial regulatory system for essential genes in yeast is described. It
      prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers
      introduced into their 5'UTRs. Exploiting direct RNA-ligand interaction renders
      auxiliary protein factors unnecessary. Therefore, our approach is strain
      independent and not susceptible to interferences by heterologous expressed
      regulatory proteins. We use a simple PCR-based strategy, which allows easy
      tagging of any target gene and the level of gene expression can be adjusted due
      to various tc aptamer-regulated promoters. As proof of concept, five differently
      expressed genes were targeted, two of which could not be regulated previously. In
      all cases, adding tc completely prevented growth and, as shown for Nop14p,
      rapidly abolished de novo protein synthesis providing a powerful tool for
      conditional regulation of yeast gene expression.

PMID- 19592424
TI  - Transcription regulation of restriction-modification system Ecl18kI.
AB  - Restriction-modification (R-M) system Ecl18kI is representative of R-M systems
      whose coordinated transcription is achieved through a separate DNA-binding domain
      of the methyltransferase. M.Ecl18kI recognizes an operator sequence located in
      the noncoding region that separates the divergently transcribed R and M genes.
      Here we show that, contrary to previous predictions, the two ecl18kI promoters
      are not divergent, but actually face one another. The binding of M.Ecl18kI to its
      operator prevents RNA polymerase (RNAP) binding to the M promoter by steric
      exclusion, but has no direct effect on RNAP interaction with the R promoter. The
      start point for R transcription is located outside of the intergenic region,
      opposite the initiation codon of the M gene. Regulated transcription of the
      potentially toxic ecl18kI R gene is accomplished (i) at the stage of promoter
      complex formation, through direct competition from complexes formed at the M
      promoter, and (ii) at the stage of promoter clearance, since R promoter-bound
      RNAP escapes the promoter more slowly than RNAP bound to the M promoter.

PMID- 19592425
TI  - Computational identification of potential molecular interactions in Arabidopsis.
AB  - Knowledge of the protein interaction network is useful to assist molecular
      mechanism studies. Several major repositories have been established to collect
      and organize reported protein interactions. Many interactions have been reported
      in several model organisms, yet a very limited number of plant interactions can
      thus far be found in these major databases. Computational identification of
      potential plant interactions, therefore, is desired to facilitate relevant
      research. In this work, we constructed a support vector machine model to predict
      potential Arabidopsis (Arabidopsis thaliana) protein interactions based on a
      variety of indirect evidence. In a 100-iteration bootstrap evaluation, the
      confidence of our predicted interactions was estimated to be 48.67%, and these
      interactions were expected to cover 29.02% of the entire interactome. The
      sensitivity of our model was validated with an independent evaluation data set
      consisting of newly reported interactions that did not overlap with the examples
      used in model training and testing. Results showed that our model successfully
      recognized 28.91% of the new interactions, similar to its expected sensitivity
      (29.02%). Applying this model to all possible Arabidopsis protein pairs resulted
      in 224,206 potential interactions, which is the largest and most accurate set of
      predicted Arabidopsis interactions at present. In order to facilitate the use of
      our results, we present the Predicted Arabidopsis Interactome Resource, with
      detailed annotations and more specific per interaction confidence measurements.
      This database and related documents are freely accessible at
      http://www.cls.zju.edu.cn/pair/.

PMID- 19592428
TI  - Migration and mental health: a study of low-income Ethiopian women working in
      Middle Eastern countries.
AB  - BACKGROUND: Few studies have explored influences on mental health of migrants
      moving between non-Western countries. METHODS: Focus group discussions were used
      to explore the experiences of Ethiopian female domestic migrants to Middle
      Eastern countries, comparing those who developed severe mental illness with those
      remaining mentally well. DISCUSSION: Prominent self-identified threats to mental
      health included exploitative treatment, enforced cultural isolation, undermining
      of cultural identity and disappointment in not achieving expectations.
      Participants countered these risks by affirming their cultural identity and
      establishing socio-cultural supports. CONCLUSIONS: Mental health of migrant
      domestic workers may be jeopardized by stressors, leading to experience of social
      defeat.

PMID- 19592427
TI  - Integration of nidotherapy into the management of mental illness and antisocial
      personality: a qualitative study.
AB  - BACKGROUND: Nidotherapy is a new treatment aimed at the systematic alteration of
      the environment in order to make a better fit for a person with chronic mental
      health difficulties. Preliminary work has suggested that it might have particular
      value in those with antisocial personality disorder. AIMS: To examine the views
      of patients with mental illness combined with antisocial personality features
      about the acceptability and value of nidotherapy when given over a six-month
      period as an adjunct to conventional care. METHOD: A two-phase study was used.
      First, a set of key informant interviews was carried out to determine how
      nidotherapy was perceived in order to identify potentially important themes.
      Specific topic guides derived from these themes were drawn up for use in the
      second stage of the study, involving semi-structured interviews with a sample of
      patients, members of their care teams and their nidotherapists. Nine patients
      were purposively selected to ensure that a range of demographic and clinical
      factors was covered. RESULTS: Analysis of the results showed that the common
      threads of the perception of nidotherapy were that it was both feasible and
      acceptable to those with antisocial personality disturbance and that the
      nidotherapists were felt to be valuable allies in what was otherwise seen as a
      hostile world. It was also seen to improve adherence to other therapies. It was
      much less valuable when the staff on the clinical teams were not able to embrace
      the collaborative approach necessary with this therapy. CONCLUSION: Nidotherapy
      is an acceptable form of management and was perceived in this study to have
      largely positive results for both patients and clinical teams as it offered
      intervention beyond that provided by conventional teams. It was felt to require
      more than six months of treatment and was less successful when there was
      inadequate communication between the nidotherapist and clinical teams and when
      the philosophy of care was not congruent.

PMID- 19592426
TI  - Arabidopsis separase functions beyond the removal of sister chromatid cohesion
      during meiosis.
AB  - Separase is a capase family protease that is required for the release of sister
      chromatid cohesion during meiosis and mitosis. Proteolytic cleavage of the alpha
      kleisin subunit of the cohesin complex at the metaphase-to-anaphase transition is
      essential for the proper segregation of chromosomes. In addition to its highly
      conserved role in cleaving the alpha-kleisin subunit, separase appears to have
      acquired additional diverse activities in some organisms, including involvement
      in mitotic and meiotic anaphase spindle assembly and elongation, interphase
      spindle pole body positioning, and epithelial cell reorganization. Results from
      the characterization of Arabidopsis (Arabidopsis thaliana) separase (ESP)
      demonstrated that meiotic expression of ESP RNA interference blocked the proper
      removal of cohesin from chromosomes and resulted in the presence of a mixture of
      fragmented chromosomes and intact bivalents. The presence of large numbers of
      intact bivalents raised the possibility that separase may also have multiple
      roles in Arabidopsis. In this report, we show that meiotic expression of ESP RNA
      interference blocks the removal of cohesin during both meiosis I and II, results
      in alterations in nonhomologous centromere association, disrupts the radial
      microtubule system after telophase II, and affects the proper establishment of
      nuclear cytoplasmic domains, resulting in the formation of multinucleate
      microspores.

PMID- 19592429
TI  - Exploring the hypothesis of ethnic practice as social capital: violence among
      Asian/Pacific Islander youth in Hawaii.
AB  - BACKGROUND: Studies of youth violence have usually examined social capital using
      qualitative methods, but remain limited by small sample sizes. In addition, few
      studies examine violence among Asian/Pacific Islander (API) youth, even though
      they are one of the fastest-growing youth populations in the USA. AIMS: To
      contribute to a better understanding of culture and ethnicity in youth violence
      among Asian Americans and Pacific Islanders by quantifying ethnic forms of social
      capital. METHODS: We use an n = 326 sample of three API groups from Oahu, Hawaii.
      Defining social capital as ethnic practice, we test Filipino, Hawaiian and Samoan
      forms of youth social capital on intimate and non-intimate violence. RESULTS:
      Bivariate findings associate lower violence with language ability among
      Filipinos, coming-of-age practices among Hawaiians, and community leader
      engagement among Samoans. Multivariate tests showed language to be the strongest
      correlation. Bivariate tests also suggested potentially risky forms of social
      capital. CONCLUSIONS: results lead us to hypothesize that social capital that
      deliberately places individuals within their respective ethnic communities are
      risk-reducing, as are those that promote formal ethnic community structures.
      Those that formalize ethnic practice and social capital into commercial
      activities may be associated with higher risk of violence. Given the relatively
      small sample size and the exploratory approach for the present investigation,
      further research is needed to determine whether the findings can be replicated
      and to extend the findings of the present preliminary study.

PMID- 19592430
TI  - The relationship between elderly suicide rates and the internet: a cross-national
      study.
AB  - BACKGROUND: Suicide rates generally increase with age. Internet websites and chat
      rooms have been reported both to promote suicides and to have a positive
      beneficial effect on suicidal individuals. The role of the internet in elderly
      suicides has not been studied. METHODS: The relationship between elderly suicide
      rates and the prevalence of internet users was examined in a cross-national study
      using data from the World Health Organization and the United Nations website.
      RESULTS: The prevalence of internet users was significantly and positively
      correlated with suicide rates in both genders in the age bands 65-74 years and
      75+ years. On multiple regression analysis the prevalence of internet users was
      independently associated with suicide rates in both genders in both age bands.
      CONCLUSION: Caution should be exercised in the attribution of a causal
      relationship and the direction of this relationship because of the cross
      sectional and ecological study design whereby the findings are subject to
      ecological fallacy. However, the findings identify and support a need for further
      research.

PMID- 19592431
TI  - Traumatic events and mental health in the community: a New Zealand study.
AB  - BACKGROUND: Adverse mental health effects in response to a variety of distressing
      events in specific populations are well documented. However, comparatively little
      research has been conducted within large community samples outside North America.
      AIMS: To assess the prevalence and psychological impact of specific traumatic
      events in a New Zealand community sample. METHODS: Prevalence and psychological
      impact of 12 traumatic events was examined in a community sample of 1,500 New
      Zealand adults using a three-stage cluster sampling method. Traumatic events,
      psychological distress, psychological well-being, and post-traumatic stress
      disorder symptoms were assessed using modified versions of the Traumatic Stress
      Schedule, Mental Health Inventory, and Civilian Mississippi Scale. The effects of
      age, gender and ethnicity were controlled for while assessing impact of traumatic
      events. RESULTS: Sixty-one per cent of the sample experienced trauma events in
      their lifetime, with 9% experiencing events in the past year. Accident-related
      events were most common in the present sample. Violent crime produced the
      greatest impact. Tests of interactions involving age, gender, and ethnicity were
      not significant. CONCLUSIONS: New Zealand community-residing individuals
      experience post-traumatic stress symptoms, reduced psychological well-being, and
      increased psychological distress following the experience of violent crime and
      accidents specifically. Study limitations and suggestions for future research are
      discussed.

PMID- 19592432
TI  - Assessing mental health outcomes of political violence and civil unrest in Peru.
AB  - BACKGROUND: Sustained political violence (SPV) may have long-term effects. AIMS:
      To assess mental and residual effects of exposure to SPV. To validate a post
      traumatic stress disorder (PTSD) assessment tool in Quechua-speaking Peru.
      METHOD: Survey of 373 individuals aged 15 and over using the General Health
      Questionnaire (GHQ-12), Hopkins Symptom Checklist (HSCL-25) and a Trauma
      Questionnaire (TQ), derived from the Harvard Trauma Questionnaire.
      Sociodemographics were recorded. Reliability was assessed. Data reduction used
      factor analysis and modelling multiple regressions. RESULTS: A quarter of the
      sample had symptoms compatible with PTSD. Questionnaire reliability ranged from
      0.81 to 0.89. Factor analysis confirmed high construct validity for TQ and HSCL
      25. Modelling showed a strong association of PTSD-related symptoms and
      expressions of distress with the degree of exposure to SPV, especially among
      returnees. CONCLUSIONS: Long-term consequences of exposure to SPV take the form
      of PTSD, anxiety and depressive disorders, and culturally formulated expressions
      of distress. Some implications for clinicians are discussed.

PMID- 19592433
TI  - Prevalence of anxiety, depression and associated factors among pregnant women of
      Hyderabad, Pakistan.
AB  - BACKGROUND: Few studies have examined the relationship between antenatal
      depression, anxiety and domestic violence in pregnant women in developing
      countries, despite the World Health Organization's estimates that depressive
      disorders will be the second leading cause of the global disease burden by 2020.
      There is a paucity of research on mood disorders, their predictors and sequelae
      among pregnant women in Pakistan. AIMS: To determine the prevalence of anxiety
      and depression and evaluate associated factors, including domestic violence,
      among pregnant women in an urban community in Pakistan. METHODS: All pregnant
      women living in identified areas of Hyderabad, Pakistan were screened by
      government health workers for an observational study on maternal characteristics
      and pregnancy outcomes. Of these, 1,368 (76%) of eligible women were administered
      the validated Aga Khan University Anxiety Depression Scale at 20-26 weeks of
      gestation. RESULTS: Eighteen per cent of the women were anxious and/or depressed.
      Psychological distress was associated with husband unemployment (p = 0.032),
      lower household wealth (p = 0.027), having 10 or more years of formal education (
      p = 0.002), a first (p = 0.002) and an unwanted pregnancy ( p < 0.001). The
      strongest factors associated with depression/anxiety were physical/sexual and
      verbal abuse; 42% of women who were physically and/or sexually abused and 23% of
      those with verbal abuse had depression/anxiety compared to 8% of those who were
      not abused. CONCLUSIONS: Anxiety and depression commonly occur during pregnancy
      in Pakistani women; rates are highest in women experiencing sexual/physical as
      well as verbal abuse, but they are also increased among women with unemployed
      spouses and those with lower household wealth. These results suggest that
      developing a screening and treatment programme for domestic violence and
      depression/anxiety during pregnancy may improve the mental health status of
      pregnant Pakistani women.

PMID- 19592435
TI  - Cultural appropriateness of the Family Assessment Device (FAD) in the case of
      ethnic Armenian adolescents in Lebanon.
AB  - BACKGROUND: The purpose of this study is to report on the cultural
      appropriateness of the 60-item Armenian version of the Family Assessment Device
      (FAD) among ethnic Armenian adolescents in the ethnically and religiously
      pluralist Lebanon. METHOD: A total of 558 Armenian adolescents in Grades 10, 11
      and 12 completed the Armenian FAD scale and the Self-Family Closeness (SFC) scale
      in a randomized order. The internal consistencies and intercorrelations of the
      Armenian FAD domains were examined, as were their correlations with the SFC
      ratings. RESULTS: The Armenian FAD and its General Functioning subscale showed
      excellent internal consistencies (alpha = 0.89 and alpha = 0.80, respectively),
      whereas the reliabilities were satisfactory for the family domains of
      Communication and Role functioning but less than satisfactory for the Affective
      Responsiveness , Problem Solving, Affective Involvement and Behaviour Control
      domains. The Armenian FAD scale and its subscales correlated with each other and
      with SFC ratings (r = -0.55 for Armenian FAD scale; r = -0.57 for General
      Functioning), and showed sensitivity to gender differences, females reporting
      better family functioning than males. CONCLUSIONS: Overall, the findings support
      the cultural appropriateness of the 12-item Armenian FAD General Functioning
      subscale and its advantage over the 60-item scale. The findings also suggest the
      need to rethink the items of the four Armenian FAD domains with low internal
      consistencies for their increased cultural relevance in the case of Armenian
      adolescents in Lebanon.

PMID- 19592434
TI  - Predicting behavioural intentions to those with mental illness: the role of
      attitude specificity and norms.
AB  - BACKGROUND: Social psychological research suggests that prediction of behavioural
      intentions towards those with mental illness could be increased by assessing
      attitudes towards specific actions or behaviours and by including a measure of
      perceived normative expectations by others concerning such behaviours. AIMS: To
      investigate whether attitudes towards specific behaviours and perceived normative
      expectations improve prediction of behavioural intentions towards a person with
      mental illness. METHODS: Two studies were carried out; one with university
      undergraduates and one with community service club members. Each included
      assessments of attitudes towards a person described as having a mental illness;
      attitudes towards specific behaviours reflecting social distance; perceived
      descriptive and injunctive norms with reference to those behaviours; and
      behavioural intentions. RESULTS: Attitude towards the specific behaviour
      frequently showed a higher correlation with behavioural intentions than did
      attitude towards the person. Inclusion of perceived norms also improved
      prediction of behavioural intention. CONCLUSIONS: The prediction of behavioural
      intentions towards those with mental illness may be improved by increasing the
      specificity of the attitude measures to the behavioural intentions being
      predicted and including measures of perceived norms. Furthermore, the
      effectiveness of efforts to reduce the stigma of mental illness may be increased
      by addressing their impact on perceived norms.

PMID- 19592436
TI  - Views and experiences of family/whanau carers of psychiatric service users on
      diagnosis and classification.
AB  - BACKGROUND: Family (whanau) and other carers can play a central part in the
      natural history of psychiatric service users. Diagnoses or the classification of
      mental disorders play a significant role in communications between clinicians,
      psychiatric service users, and family. Despite that centrality, the views and
      experiences of family on the utility of the present classification systems have
      been little studied. AIMS: This study aimed to document the understanding and
      opinions of families/whanau on the utility of diagnostic labels as they observed
      them being applied to their family members. METHOD: This is a qualitative study.
      The families of two cultural groups (New Zealand Maori and non-Maori) of
      psychiatric service users were interviewed using a structured approach. RESULTS:
      A number of themes on the utility of the diagnostic systems emerged. The single
      most powerful message being that how the diagnostic labels were communicated, and
      how they were utilized in the patient management planning, were of paramount
      importance. There were some cross-cultural differences. From Maori, there was a
      particular plea for a greater incorporation of culturally syntonic concepts.
      CONCLUSION: Family/whanau had positive views of the contributions current
      diagnostic practices make to patient care. The study elicited the view that more
      contextual issues, and not just phenomenology, should be taken into account in
      the development of diagnostic systems.

PMID- 19592437
TI  - Prolonged grief disorder, depression, and posttraumatic stress disorder among
      bereaved Kosovar civilian war survivors: a preliminary investigation.
AB  - BACKGROUND: This study aimed at examining diagnostic concordance between
      Prolonged Grief Disorder (PGD), Major Depressive Disorder (MDD), and
      Posttraumatic Stress Disorder (PTSD) among bereaved war survivors who had lost
      relatives due to war-related violence. METHOD: We investigated the rates of PGD
      and its association with PTSD and MDD among 60 bereaved people who had lost first
      degree relatives due to war-related violence seven years ago and had also
      experienced other war-related events. RESULTS: The results indicated that 38.3%
      of the sample fulfilled the criteria for PGD, 55.0% for PTSD, and 38.3% for MDD.
      Thirty per cent of the participants without PTSD and 21.6% of those without MDD
      met criteria for PGD. Women were more likely to have PGD than men. The immediate
      threat to life was significantly associated with an elevated risk for PTSD and
      MDD, but not PGD. CONCLUSION: The findings suggest that many cases of PGD would
      be missed by an exclusive focus on PTSD among bereaved war survivors.

PMID- 19592439
TI  - Lay theories of bipolar disorder: the causes, manifestations and cures for
      perceived bipolar disorder.
AB  - This study aimed to investigate lay theories of the cause and treatment of
      bipolar disorder, and the recognition of its symptoms. This questionnaire-based
      study included vignette descriptions of mental disorders and 70 items relating to
      bipolar disorder. It was completed by 173 participants. Bipolar disorder was
      recognized less than depression but at the same rate as schizophrenia. Contrary
      to previous research, analysis showed that lay beliefs of the causes of bipolar
      disorder generally concur with scientific academic theories. Drug treatment was
      favoured as a cure rather than psychotherapy. Theories of cause and treatment
      were logically correlated. Overall, the results suggest that lay people have
      reasonably informed beliefs about the causes and treatments of bipolar disorder,
      however recognition of the symptoms is poor.

PMID- 19592438
TI  - Ataque de nervios as a marker of social and psychiatric vulnerability: results
      from the NLAAS.
AB  - BACKGROUND: This article presents the fi rst epidemiological portrait of ataques
      de nervios among Latinos in the mainland United States. Much of the previous
      literature has focused on Puerto Ricans in Puerto Rico and New York City. AIMS:
      This study examines the social and psychiatric correlates of ataque de nervios in
      a nationally representative sample of Latinos in the United States. METHODS: This
      study employs data from the Latino sample (N = 2554) of the National Latino and
      Asian American Study (NLAAS). Analyses examined the associations between ataques
      de nervios and a range of social and migration variables, as well as psychiatric
      diagnoses and measures of mental health need. RESULTS: Ataques de nervios were
      reported by 7-15% of the different Latino groups, with Puerto Ricans reporting
      the highest frequency. Ataques de nervios were more frequent in women, those with
      disrupted marital status, and those more acculturated to the US. The frequency of
      those who met criteria for affective, anxiety and substance abuse disorders was
      higher among those reporting an ataque de nervios. CONCLUSION: Ataque de nervios
      can serve as an important indicator of social and psychiatric vulnerability in
      future epidemiological and clinical studies with Latino populations.

PMID- 19592440
TI  - Subjective and objective indicators of recovery in severe mental illness: a cross
      sectional study.
AB  - BACKGROUND: This study aimed to determine whether subjective dimensions of
      recovery such as empowerment are associated with self-report of more objective
      indicators such as level of participation in the community and income from
      employment. A secondary aim was to investigate the extent to which diagnosis or
      other consumer characteristics mediated any relationship between these variables.
      METHODS: The Community Integration Measure, the Empowerment Scale, the Recovery
      Assessment Scale, and the Camberwell Assessment of Needs Short Appraisal Schedule
      were administered to a convenience sample of 161 consumers with severe mental
      illness. RESULTS: The majority of participants had a primary diagnosis of
      schizophreniform, anxiety/depression or bipolar affective disorder. The
      Empowerment Scale was quite strongly correlated with the Recovery Assessment
      Scale and the Community Integration Measure. Participants with a diagnosis of
      bipolar affective disorder had significantly higher recovery and empowerment
      scores than participants with schizophrenia or depression. Both empowerment and
      recovery scores were significantly higher for people engaged in paid employment
      than for those receiving social security benefits. CONCLUSIONS: The measurement
      of subjective dimensions of recovery such as empowerment has validity in
      evaluation of global recovery for people with severe mental illness. A diagnosis
      of bipolar disorder is associated with higher scores on subjective and objective
      indicators of recovery.

PMID- 19592441
TI  - Depression in obese persons before starting complex group weight-reduction
      programme.
AB  - BACKGROUND: The aim of the present study was to assess the prevalence of
      depression in subjects before starting a weight-reduction programme. METHODS: The
      study group involved 173 obese subjects aged 47.0 +/- 16.5 years, body mass index
      (BMI) 36.1 +/- 6.3, weight 96.2 +/- 18.3 kg. The body weight and height were
      measured and BMI was calculated. Beck's Depression Inventory (BDI) was used for
      the evaluation of depressive symptoms. RESULTS: Severe depression was diagnosed
      in 84 subjects (mean BMI 37.5 +/- 6.3, mean weight 98.1 +/- 17.6 kg, age 48.7 +/-
      16.0, 22.2 +/- 1.6 points), mild depression was diagnosed in 65 subjects (mean
      BMI 34.7 +/- 4.8, mean weight 95.3 +/- 18.1 kg, age 45.9 +/- 16.6; 10.8 +/- 2.0
      points), and 24 subjects (mean BMI 35.0 +/- 8.7, mean weight 92.2 +/- 21.1 kg,
      age 44.0 +/- 17.5, 6.5 +/- 0.5 points) did not have depression. We observed
      differences in BMI between subjects without depression and severe depression (p <
      0.05) and between mild and severe depression. We did not observe differences of
      age and body mass between these subgroups. Correlations between weight, BMI and
      BDI score were found in all subjects. CONCLUSION: Depression often accompanies
      obesity. The depression levels increased in morbidly obese persons in comparison
      to moderately obese patients.

PMID- 19592442
TI  - A culturally relevant conceptualization of depression: an empirical examination
      of the factorial structure of the Vietnamese Depression Scale.
AB  - BACKGROUND: Despite the high risk of depression among Vietnamese refugees, there
      has been insufficient attention to the psychometric properties of the most
      utilized scale, the Vietnamese Depression Scale (VDS: Kinzie et al., 1982). AIM:
      The primary aim of the study is to empirically derive the factorial structure of
      the VDS to support its use as a culturally responsive depression screening tool
      in community samples of Vietnamese adults. METHOD: The factorial structure,
      reliability, and associations of the VDS factors with recognized socio
      demographic correlates were examined using data collected from interviews with a
      non-probability community sample of 180 Vietnamese refugee adults in the Houston
      area. RESULTS: The empirically derived factorial structure of the VDS
      approximated the theorized conceptualization of depression introduced by the
      scale's originators. Three factors (depressed affect, somatic symptoms, and
      cultural-specific symptoms) accounted for 65% of the variance. As hypothesized,
      the VDS factors correlated with age and acculturation variables. CONCLUSION:
      Overall results suggest that the conceptualization of depression among this
      sample of Vietnamese refugees has both universal and culturally specific
      features. Implications for providing culturally responsive mental health services
      are offered.

PMID- 19592443
TI  - The role of the social network in psychosomatic day care and inpatient care.
AB  - BACKGROUND: There are many studies on the relationship between social ties and
      mental health but there is so far no research on the role of the social network
      in relation to inpatient or day-care treatment. This is of interest as in
      inpatient treatment patients are taken out of their social network completely,
      while in day care they are left in their natural environment. AIMS: This study
      investigates whether there are interactions between the mode of care (inpatient
      versus day-care treatment) and characteristics of the social network. METHODS:
      Fifty seven matched pairs (inpatients, day-care patients) with mental or
      psychosomatic disorders were assessed with the Multidimensional Social Contact
      Circle Questionnaire (MuSC-Q). Patients and their partners were asked to
      characterize their mutual relationship. RESULTS: Patients who were married or
      living together with a partner were more often treated in day care. Social
      integration and social strain similarly decreased during inpatient and day-care
      treatment whereas emotional support increased. While both patient groups
      evaluated the relationship to their partner similarly, the partners of day-care
      patients saw more strain on their relationship during hospitalization.
      CONCLUSION: The results suggest that patients who do not live alone prefer the
      day-care treatment facility. Patients in both modes of care at the end see their
      partnership as more supportive. For their partners, day care means that they have
      greater burdens to cope with when the patient is in treatment and still at home.

PMID- 19592444
TI  - Psychometric properties of the Chinese version of the Self-Reporting
      Questionnaire 20 (SRQ-20) in community settings.
AB  - BACKGROUND: Community mental health services in China are in need of a brief,
      valid instrument to identify mental disorders. Many studies support the Self
      Reporting Questionnaire 20 (SRQ-20) as a cost-effective instrument with which to
      measure community mental health, but there have been no previous studies
      conducted with the Chinese version of SRQ-20. In this paper, the psychometric
      properties of the Chinese version of SRQ-20 in community settings were
      investigated. METHOD: SRQ-20 was used to evaluate 959 participants from 10
      communities of Hangzhou City and 60 participants from two community primary care
      centres for the presence of mental disorders. Discriminative, concurrent, and
      construct validity as well as internal consistency and screening properties of
      SRQ-20 were evaluated. RESULTS: Cronbach's alpha for SRQ-20 was 0.90 for primary
      care and 0.91 for the community. Item-total correlation coefficients ranged from
      0.40 to 0.73 in primary care, and from 0.51 to 0.69 in the community. The test
      retest correlation coefficient was 0.93 in primary care and 0.94 in the
      community. Varimax-rotated principal component analysis of the SRQ-20 items
      yielded three factors: depressive symptoms, anxiety symptoms and somatic
      symptoms. The area under the ROC curve was 0.83 (SE =0.04, 95% CI 0.75-0.90) for
      the community and primary care samples. The optimal cut-off point for SRQ-20 was
      6/7 yielding sensitivity of 93% and specificity of 62%. CONCLUSION: SRQ-20
      appears to be a reliable and valid measure of mental disorders in the community
      in China.

PMID- 19592445
TI  - Gambling behaviours and motivations: a cross-cultural study of Chinese and
      Caucasians in Australia.
AB  - BACKGROUND: Research on gambling behaviours among the Chinese, especially
      compared to Caucasians, is lacking. AIMS: and METHODS: Gambling behaviours and
      motivations between community-based Chinese (n = 199) and Caucasians (n = 306)
      living in Australia were compared. RESULTS: There were significant differences
      between Caucasians and Australian Chinese in relation to gambling behaviours and
      types of motivations that could predict problem gambling between the two groups.
      CONCLUSIONS: The findings provide relevant information in understanding gambling
      behaviours and motivations among the Chinese, as well as a step towards the
      development of tailored preventive and treatment interventions for problem
      gambling in this population.

PMID- 19592446
TI  - Job satisfaction and burnout among staff working in community-based personality
      disorder services.
AB  - AIMS: To examine levels of burnout among staff working in community-based
      services for people with personality disorder (PD) and to explore factors which
      add to or lower the risk of burnout among people working in such services.
      METHODS: In-depth interviews with staff working at 11 dedicated community-based
      personality disorder services in England together with a cross-sectional staff
      survey using the Maslach Burnout Inventory. RESULTS: Levels of burnout were
      generally lower than those reported in previous studies among mental health
      workers and levels of personal accomplishment were higher. Staff reported
      positive as well as negative experiences of working with people with PD. Strong
      team-work, clear leadership and opportunities for reflective practice were
      thought to protect staff from burnout. CONCLUSIONS: The low levels of burnout we
      found may reflect the early stage of the development of these services. However,
      it is also possible that working with people with PD does not in itself lead to
      burnout, especially when services are organized to share and contain work-related
      anxiety.

PMID- 19592447
TI  - An evaluation of new services for personality-disordered offenders: staff and
      service user perspectives.
AB  - BACKGROUND: Little is known about effective treatment for personality-disordered
      (PD) offenders. We aimed to obtain the perspective of service users and staff on:
      (a) the experience of receiving treatment; and (b) the experience of delivering
      treatment, within new forensic services for PD offenders. MATERIAL: Thematic
      analysis was applied to qualitative interviews with 30 service users and 22
      staff. DISCUSSION: Service users perceived that they were making positive changes
      in the areas of anger management, communication, self-harm, self-esteem and
      insight into their difficulties. Undertaking the clinical work was extremely
      stressful for staff. CONCLUSIONS: Forensic PD services may be having an important
      impact on the quality of service users' lives. Whether treatment is successful in
      reducing long-term risk to others remains to be seen, and the cost-effectiveness
      of these services needs to be examined.

PMID- 19592448
TI  - Suicide victims' last contact with the primary care physician: report from
      Slovenia.
AB  - BACKGROUND: Previous studies have reported that many suicide victims have had
      contact with their physicians a week or month prior to their suicide. AIMS: To
      assess the date of the last appointment (and complaint) of suicide victims in the
      Skofja Loka region within Slovenia. METHOD: We included all suicide victims in
      the region in the period 1993-2003. Each of the cases was assigned the closest
      control in terms of age and gender. Medical death certificates served as a source
      of demographic data information and information about suicide method. From
      personal medical records we obtained the date of the last appointment (and the
      complaint) with the primary care physician. The same was done for the control
      group. The groups were compared for their last appointment with their physician
      (date and complaint). RESULTS: Thirty out of 77 suicide victims visited their
      physician in the last month before suicide (14/77 in the last week); only 16/77
      controls did so before the index day (3/77 in the last week). In 30% of suicide
      victims, the reason for the last visit was mental health problems (only 3% in the
      control group). CONCLUSION: The results emphasize the important role of primary
      care physicians in suicide prevention.

PMID- 19592449
TI  - The association of immigrant- and non-immigrant-specific factors with mental ill
      health among immigrants in Sweden.
AB  - BACKGROUND: It has often been shown that immigrants are particularly at risk for
      mental ill health. The aim of the study was to investigate the association of
      immigrant- and non-immigrant-specific factors with mental ill health within a
      diverse immigrant population. METHOD: An extensive questionnaire was sent out to
      a stratified random sample of three immigrant populations from Finland, Iraq and
      Iran. The 720 respondents completed a Swedish, Arabic or Farsi (Persian) version
      of the questionnaire including the WHO (10) Well-Being Index and the HSCL-25.
      RESULTS: The results indicate that mental ill health among immigrants is
      independently associated with non-immigrant-specific factors (i.e. high number of
      types of traumatic episodes, divorced/widowed, poor social network, economic
      insecurity and being female) and immigrant-specific factors (i.e. low level of
      sociocultural adaptation). These results were obtained regardless of whether
      mental ill health was operationalized as low subjective well-being or a high
      symptom level of anxiety/depression. CONCLUSIONS: These findings support the
      notion that mental ill health among immigrants is a multi-faceted phenomenon that
      needs to be tackled within a wide range of sectors - e.g. the healthcare system,
      the social service sector and, of course, the political arena.

PMID- 19592450
TI  - The future of targeted therapies in ovarian cancer.
AB  - Ovarian cancer is the second most common gynecological malignancy and the leading
      cause of death from gynecological cancer. Most women present with advanced
      disease with little prospect for cure. There have been some advances in surgical
      and chemotherapeutic strategies, but these approaches have led to only minor
      improvements in outcome. There remains a significant risk for recurrence and
      resistance to therapy, and hence there is a need to improve upon the current
      treatment options. Molecularly directed therapy aims to target tumor cells and
      the tumor microenvironment by blocking specific molecular changes in the cancer.
      The most promising agents so far are the antiangiogenic agents and polyadenosine
      diphosphate-ribose polymerase inhibitors. This article reviews the various
      targeted therapeutic approaches under clinical investigation in ovarian cancer
      and the challenges facing their future success in the clinic.

PMID- 19592456
TI  - Pathogenesis and transmission of the novel swine-origin influenza virus A/H1N1
      after experimental infection of pigs.
AB  - Influenza virus A/H1N1, which is currently causing a pandemic, contains gene
      segments with ancestors in the North American and Eurasian swine lineages. To get
      insights into virus replication dynamics, clinical symptoms and virus
      transmission in pigs, we infected animals intranasally with influenza virus
      A/Regensburg/D6/09/H1N1. Virus excretion in the inoculated pigs was detected in
      nasal swabs from 1 day post-infection (p.i.) onwards and the pigs developed
      generally mild symptoms, including fever, sneezing, nasal discharge and
      diarrhoea. Contact pigs became infected, shed virus and developed clinical
      symptoms similar to those in the inoculated animals. Plasma samples of all
      animals remained negative for virus RNA. Nucleoprotein- and haemagglutinin H1
      specific antibodies could be detected by ELISA 7 days p.i. CD4(+) T cells became
      activated immediately after infection and both CD4(+) and CD8(+) T-cell
      populations expanded from 3 to 7 days p.i., coinciding with clinical signs.
      Contact chickens remained uninfected, as judged by the absence of virus
      excretion, clinical signs and seroconversion.

PMID- 19592451
TI  - Phthalates impair germ cell number in the mouse fetal testis by an androgen- and
      estrogen-independent mechanism.
AB  - Data from experiments conducted almost exclusively in the rat have established
      that some phthalates have deleterious effects on the fetal testis probably due to
      their antiandrogenic and/or estrogenic effects, but their mechanisms of action
      remain unknown. A recent study reported that phthalates also have deleterious
      effects on human fetal testis with germ cell number, but not steroidogenesis
      altered. Therefore, we used organ culture of fetal testes at different stages of
      development to analyze the direct effects of phthalates on both steroidogenesis
      and gonocyte development and to determine if the effects of MEHP on these
      functions reported in the rat can be extended to other mammalian species. We
      defined specific periods of sensitivity of the fetal mouse testis to MEHP for
      these two functions and showed that the effects of phthalates on steroidogenesis
      vary with the developmental stage. Conversely, the strong deleterious effects of
      phthalates on germ cells were constantly present during the active phases of
      gonocyte development and thus share no relationship with the steroidogenic
      status. Moreover, all the effects of phthalates were unchanged in testes from
      mice deficient for estrogen (ERalphaKO or ERbetaKO) or androgen (Tfm) receptors.
      In conclusion, our results demonstrate that phthalates impair mouse fetal germ
      cell number similarly to other mammalian species, but are neither estrogenic nor
      antiandrogenic molecules because their effects do not involve, directly or
      indirectly, ER or AR.

PMID- 19592457
TI  - Beta-adrenoceptor stimulation of alveolar fluid clearance is increased in rats
      with heart failure.
AB  - The alveolar epithelium plays a critical role in resolving pulmonary edema. We
      thus hypothesized that its function might be upregulated in rats with heart
      failure, a condition that severely challenges the lung's ability to maintain
      fluid balance. Heart failure was induced by left coronary artery ligation.
      Echocardiographic and cardiovascular hemodynamics confirmed its development at 16
      wk postligation. At that time, alveolar fluid clearance was measured by an
      increase in protein concentration over 1 h of a 5% albumin solution instilled
      into the lungs. Baseline alveolar fluid clearance was similar in heart failure
      and age-matched control rats. Terbutaline was added to the instillate to
      determine whether heart failure rats responded to beta-adrenoceptor stimulation.
      Alveolar fluid clearance in heart failure rats was increased by 194% after
      terbutaline stimulation compared with a 153% increase by terbutaline in control
      rats. To determine the mechanisms responsible for this accelerated alveolar fluid
      clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No
      significant upregulation was observed for these ion transporters in the heart
      failure rats. Lung morphology showed significant alveolar epithelial type II cell
      hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell
      hyperplasia is the likely explanation for the increased terbutaline-stimulated
      alveolar fluid clearance in heart failure rats. These data provide evidence for
      previously unrecognized mechanisms that can protect against or hasten resolution
      of alveolar edema in heart failure.

PMID- 19592458
TI  - NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia
      induced pulmonary hypertension in newborn piglets.
AB  - Recently, we reported that reactive oxygen species (ROS) generated by NADPH
      oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries
      (PRAs) of piglets exposed to 3 days of hypoxia (Am J Physiol Lung Cell Mol
      Physiol 295: L881-L888, 2008). An objective of the present study was to determine
      whether NOX-derived ROS also contribute to altered PRA responses at a more
      advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further
      wished to advance knowledge about the specific NOX and antioxidant enzymes that
      are altered at early and later stages of pulmonary hypertension. Piglets were
      raised in room air (control) or hypoxia for 3 or 10 days. Using a cannulated
      artery technique, we found that treatments with agents that inhibit NOX
      (apocynin) or remove ROS [an SOD mimetic (M40403) + polyethylene glycol-catalase]
      diminished responses to ACh in PRAs from piglets exposed to 10 days of hypoxia.
      Western blot analysis showed an increase in expression of NOX1 and the membrane
      fraction of p67phox. Expression of NOX4, SOD2, and catalase were unchanged,
      whereas expression of SOD1 was reduced, in arteries from piglets raised in
      hypoxia for 3 or 10 days. Markers of oxidant stress, F(2)-isoprostanes, measured
      by gas chromatography-mass spectrometry, were increased in PRAs from piglets
      raised in hypoxia for 3 days, but not 10 days. We conclude that ROS derived from
      some, but not all, NOX family members, as well as alterations in the antioxidant
      enzyme SOD1, contribute to aberrant PRA responses at an early and a more
      progressive stage of chronic hypoxia-induced pulmonary hypertension in newborn
      piglets.

PMID- 19592460
TI  - Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human
      pulmonary artery smooth muscle cells.
AB  - Angiotensin-converting enzyme (ACE) enhances the proliferation and migration of
      pulmonary artery smooth muscle cells (PASMCs), which contribute to the
      pathogenesis of hypoxic pulmonary hypertension (HPH). Previous reports have
      demonstrated that hypoxia upregulates ACE expression, but the underlying
      mechanism is unknown. Here, we found that ACE is persistently upregulated in
      PASMCs on the transcriptional level during hypoxia. Hypoxia-inducible factor
      1alpha (HIF-1alpha), a key transcription factor activated during hypoxia, was
      able to upregulate ACE protein expression under normoxia, whereas knockdown of
      HIF-1alpha expression in PASMCs inhibited hypoxia-induced ACE upregulation.
      Furthermore, HIF-1alpha can bind and transactivate the ACE promoter directly.
      Therefore, we report that ACE is a novel target of HIF-1alpha. Recently, a
      homolog of ACE, ACE2, was reported to counterbalance the function of ACE. In
      contrast to ACE, we found that ACE2 mRNA and protein levels increased during the
      early stages of hypoxia and decreased to near-baseline levels at the later stages
      after HIF-1alpha accumulation. Thus HIF-1alpha inhibited ACE2 expression, and the
      accumulated ANG II catalyzed by ACE is a key mediator in the downregulation of
      ACE2 by HIF-1alpha. Moreover, a reduction of ACE2 expression in PASMCs by RNA
      interference was accompanied by significantly enhanced proliferation and
      migration during hypoxia. We conclude that ACE is directly regulated by HIF
      1alpha, whereas ACE2 is regulated in a bidirectional way during hypoxia and may
      play a protective role during the development of HPH. In sum, these findings
      contribute to the understanding of the pathogenesis of HPH.

PMID- 19592459
TI  - Mutation of protein kinase C phosphorylation site S1076 on alpha-subunits affects
      BK(Ca) channel activity in HEK-293 cells.
AB  - Large conductance, calcium- and voltage-activated potassium (BK(Ca)) channels are
      important modulators of pulmonary vascular smooth muscle membrane potential, and
      phosphorylation of BK(Ca) channels by protein kinases regulates pulmonary
      arterial smooth muscle function. However, little is known about the effect of
      phosphorylating specific channel subunits on BK(Ca) channel activity. The present
      study was done to determine the effect of mutating protein kinase C (PKC)
      phosphorylation site serine 1076 (S1076) on transfected human BK(Ca) channel
      alpha-subunits in human embryonic kidney (HEK-293) cells, a heterologous
      expression system devoid of endogenous BK(Ca) channels. Results showed that
      mutating S1076 altered the effect of PKC activation on BK(Ca) channels in HEK-293
      cells. Specifically, the phospho-deficient mutation BK(Ca)-alpha(S1076A)/beta(1)
      attenuated the excitatory effect of the PKC activator phorbol myristate acetate
      (PMA) on BK(Ca) channels, whereas the phospho-mimetic mutation BK(Ca)
      alpha(S1076E)/beta(1) increased the excitatory effect of PMA on BK(Ca) channels.
      In addition, the phospho-null mutation S1076A blocked the activating effect of
      cGMP-dependent protein kinase G (PKG) on BK(Ca) channels. Collectively, these
      results suggest that specific putative PKC phosphorylation site(s) on human
      BK(Ca) channel alpha-subunits influences BK(Ca) channel activity, which may
      subsequently alter pulmonary vascular smooth muscle function and tone.

PMID- 19592462
TI  - Soluble guanylate cyclase agonists inhibit expression and procoagulant activity
      of tissue factor.
AB  - OBJECTIVE: Tissue factor (TF), a major initiator of blood coagulation,
      contributes to inflammation, atherosclerosis, angiogenesis, and vascular
      remodeling. Pharmacological agonists of soluble guanylate cyclase (sGC) attenuate
      systemic and pulmonary hypertension, vascular remodeling, and platelet
      aggregation. However, the influence of these novel pharmacophores on TF is
      unknown. METHODS AND RESULTS: We evaluated effects of BAY 41-2272 and BAY 58-2667
      on expression and activity of TF in human monocytes and umbilical vein
      endothelial cells (HUVECs). Both compounds reduced expression of active TF
      protein in monocytes stimulated with lipopolysaccharide, as demonstrated by
      immunoblotting and a TF procoagulant activity assay. In-cell Western assay
      revealed that this effect was associated with a marked reduction of total and
      surface TF presentation. Furthermore, BAY 41-2272 and BAY 58-2667 decreased TF
      protein expression and the TF-dependent procoagulant activity in HUVECs
      stimulated with TNF-alpha. The sGC agonists also suppressed transcriptional
      activity of NF-kappaB. A siRNA-mediated knockdown of the alpha1-subunit of sGC in
      monocytes and HUVECs confirmed that the inhibitory effect of BAY 41-2272 and BAY
      58-2667 on TF expression is mediated through the sGC-dependent mechanisms.
      CONCLUSIONS: Inhibition of TF expression and activity by sGC agonists might
      provide therapeutic benefits in cardiovascular diseases associated with enhanced
      procoagulant and inflammatory response.

PMID- 19592463
TI  - Thiol oxidative stress induced by metabolic disorders amplifies macrophage
      chemotactic responses and accelerates atherogenesis and kidney injury in LDL
      receptor-deficient mice.
AB  - BACKGROUND: Strengthening the macrophage glutathione redox buffer reduces
      macrophage content and decreases the severity of atherosclerotic lesions in LDL
      receptor-deficient (LDLR(-/-)) mice, but the underlying mechanisms were not
      clear. This study examined the effect of metabolic stress on the thiol redox
      state, chemotactic activity in vivo, and the recruitment of macrophages into
      atherosclerotic lesions and kidneys of LDL-R(-/-) mice in response to mild,
      moderate, and severe metabolic stress. METHODS AND RESULTS: Reduced glutathione
      (GSH) and glutathione disulfide (GSSG) levels in peritoneal macrophages isolated
      from mildly, moderately, and severe metabolically-stressed LDL-R(-/-) mice were
      measured by HPLC, and the glutathione reduction potential (E(h)) was calculated.
      Macrophage E(h) correlated with the macrophage content in both atherosclerotic
      (r(2)=0.346, P=0.004) and renal lesions (r(2)=0.480, P=0.001) in these mice as
      well as the extent of both atherosclerosis (r(2)=0.414, P=0.001) and kidney
      injury (r(2)=0.480, P=0.001). Compared to LDL-R(-/-) mice exposed to mild
      metabolic stress, macrophage recruitment into MCP-1-loaded Matrigel plugs
      injected into LDL-R(-/-) mice increased 2.6-fold in moderately metabolically
      stressed mice and 9.8-fold in severely metabolically-stressed mice. The
      macrophage E(h) was a strong predictor of macrophage chemotaxis (r(2)=0.554,
      P<0.001). CONCLUSIONS: Thiol oxidative stress enhances macrophage recruitment
      into vascular and renal lesions by increasing the responsiveness of macrophages
      to chemoattractants. This novel mechanism contributes at least in part to
      accelerated atherosclerosis and kidney injury associated with dyslipidemia and
      diabetes in mice.

PMID- 19592461
TI  - Regulation of soluble guanylyl cyclase-alpha1 expression in chronic hypoxia
      induced pulmonary hypertension: role of NFATc3 and HuR.
AB  - The nitric oxide/soluble guanylyl cyclase (sGC) signal transduction pathway plays
      an important role in smooth muscle relaxation and phenotypic regulation. However,
      the transcriptional regulation of sGC gene expression is largely unknown. It has
      been shown that sGC expression increases in pulmonary arteries from chronic
      hypoxia-induced pulmonary hypertensive animals. Since the transcription factor
      NFATc3 is required for the upregulation of the smooth muscle
      hypertrophic/differentiation marker alpha-actin in pulmonary artery smooth muscle
      cells from chronically hypoxic mice, we hypothesized that NFATc3 is required for
      the regulation of sGC-alpha1 expression during chronic hypoxia. Exposure to
      chronic hypoxia for 2 days induced a decrease in sGC-alpha1 expression in mouse
      pulmonary arteries. This reduction was independent of NFATc3 but mediated by
      nuclear accumulation of the mRNA-stabilizing protein human antigen R (HuR).
      Consistent with our hypothesis, chronic hypoxia (21 days) upregulated pulmonary
      artery sGC-alpha1 expression, bringing it back to the level of the normoxic
      controls. This response was prevented in NFATc3 knockout and cyclosporin
      (calcineurin/NFATc inhibitor)-treated mice. Furthermore, we identified effective
      binding sites for NFATc in the mouse sGC-alpha1 promoter. Activation of NFATc3
      increased sGC-alpha1 promoter activity in human embryonic derived kidney cells,
      rat aortic-derived smooth muscle cells, and human pulmonary artery smooth muscle
      cells. Our results suggest that NFATc3 and HuR are important regulators of sGC
      alpha1 expression in pulmonary vascular smooth muscle cells during chronic
      hypoxia-induced pulmonary hypertension.

PMID- 19592464
TI  - Syndecan-1: an inhibitor of arterial smooth muscle cell growth and intimal
      hyperplasia.
AB  - OBJECTIVE: Arterial injury induces smooth muscle cell (SMC) proliferation,
      migration, and intimal accumulation of cells and extracellular matrix. These
      processes are regulated by the administration of the glycosaminoglycans heparin
      and heparan sulfate, but little is known about the role of endogenous heparan
      sulfate proteoglycans in the vessel wall. We investigated the response to carotid
      injury of syndecan-1-null mice to assess the function of one of a conserved
      family of transmembrane heparan and chondroitin sulfate proteoglycans. METHODS
      AND RESULTS: Syndecan-1-null mice developed a large neointimal lesion after
      injury, whereas wild-type mice made little or none. This was accompanied by a
      significant increase in both medial and intimal SMC replication. Cultured
      syndecan-1-null SMCs showed a significant increase in proliferation in response
      to PDGF-BB, thrombin, FGF2, EGF, and serum. In response to thrombin, PDGF-BB, and
      serum syndecan-1-null SMCs expressed more PDGF-B chain message than did wild-type
      SMCs. Downregulation of PDGF-BB or PDGFRbeta inhibited thrombin-, PDGF-BB-, and
      serum-induced DNA synthesis in syndecan-1-null SMCs. CONCLUSIONS: These results
      suggest the possibility that syndecan-1 may limit intimal thickening in injured
      arteries by suppressing SMC activation through inhibition of SMC PDGF-B chain
      expression and PDGFRbeta activation.

PMID- 19592465
TI  - c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and
      improve cardiac function after ischemia-reperfusion injury.
AB  - OBJECTIVE: Coronary reperfusion has been the mainstay therapy for reduced infarct
      size after a heart attack. However, this intervention also results in myocardial
      injury by initiating a marked inflammatory reaction, and new treatments are
      keenly sought. METHODS AND RESULTS: The basic-region leucine zipper protein, c
      Jun is poorly expressed in the normal myocardium and is induced within 24 hours
      after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules
      (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR)
      regardless of whether it is delivered intramyocardially at the initiation of
      ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration,
      c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and
      the generation of reactive oxygen species in the reperfused myocardium. It
      inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR),
      membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive
      inflammatory cells. Dz13 also improves cardiac function without influencing
      myocardial vascularity or fibrosis. CONCLUSIONS: These findings demonstrate the
      regulatory role of c-Jun in the pathogenesis of myocardial inflammation and
      infarction following ischemia-reperfusion injury, and inhibition of this process
      using catalytic DNA.

PMID- 19592466
TI  - Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus.
AB  - OBJECTIVE: We have investigated the functional significance of conserved
      sequences within the 9p21.3 risk locus for coronary artery disease (CAD) and
      determined the relationship of 9p21.3 to expression of ANRIL and to whole genome
      gene expression. METHODS AND RESULTS: We demonstrate that a conserved sequence
      within the 9p21.3 locus has enhancer activity and that the risk variant
      significantly increases reporter gene expression in primary aortic smooth muscle
      cells. Whole blood RNA expression of the short variants of ANRIL was increased by
      2.2-fold whereas expression of the long ANRIL variant was decreased by 1.2-fold
      in healthy subjects homozygous for the risk allele. Expression levels of the long
      and short ANRIL variants were positively correlated with that of the cyclin
      dependent kinase inhibitor, CDKN2B (p15) and TDGF1 (Cripto), respectively.
      Relevant to atherosclerosis, genome-wide expression profiling demonstrated
      upregulation of gene sets modulating cellular proliferation in carriers of the
      risk allele. CONCLUSIONS: These findings are consistent with the hypothesis that
      the 9p21.3 risk allele contains a functional enhancer, the activity of which is
      altered in carriers of the risk allele. 9p21.3 may promote atherosclerosis by
      regulating expression of ANRIL, which in turn is associated with altered
      expression of genes controlling cellular proliferation pathways.

PMID- 19592467
TI  - Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via
      gene-specific permissivity of the RXR/LXR heterodimer in the liver.
AB  - OBJECTIVE: Bexarotene (Targretin) is a clinically used antitumoral agent which
      exerts its action through binding to and activation of the retinoid-X-receptor
      (RXR). The most frequent side-effect of bexarotene administration is an increase
      in plasma triglycerides, an independent risk factor of cardiovascular disease.
      The molecular mechanism behind this hypertriglyceridemia remains poorly
      understood. METHODS AND RESULTS: Using wild-type and LXR alpha/beta-deficient
      mice, we show here that bexarotene induces hypertriglyceridemia and activates
      hepatic LXR-target genes of lipogenesis in an LXR-dependent manner, hence
      exerting a permissive effect on RXR/LXR heterodimers. Interestingly, RNA analysis
      and Chromatin Immunoprecipitation assays performed in the liver reveal that the
      in vivo permissive effect of bexarotene on the RXR/LXR heterodimer is restricted
      to lipogenic genes without modulation of genes controlling cholesterol
      homeostasis. CONCLUSIONS: These findings demonstrate that the
      hypertriglyceridemic action of bexarotene occurs via the RXR/LXR heterodimer and
      show that RXR heterodimers can act with a selective permissivity on target genes
      of specific metabolic pathways in the liver.

PMID- 19592468
TI  - Nrf2 protects against maladaptive cardiac responses to hemodynamic stress.
AB  - BACKGROUND: Reactive oxygen species (ROS) play an important role in the
      maintenance of cardiovascular homeostasis. The present study sought to determine
      whether nuclear factor erythroid-2 related factor 2 (Nrf2), a master gene of the
      endogenous antioxidant defense system, is a critical regulator of the cardiac
      hypertrophic response to pathological stress. METHODS AND RESULTS: Cardiac
      hypertrophy and dysfunction were established in mice by transverse aortic
      constriction (TAC). Nrf2 expression was transiently increased and then declined
      to the basal level while impairment of cardiac function proceeded. The knockout
      of Nrf2 (Nrf2(-/-)) did not cause any apparent structural and functional
      abnormalities in the unstressed heart. However, Nrf2(-/-) mice after TAC
      developed pathological cardiac hypertrophy, significant myocardial fibrosis and
      apoptosis, overt heart failure, and increased mortality, which were associated
      with elevated myocardial levels of 4-hydroxy-2-nonenal and 8
      hydroxydeoxyguanosine and a complete blockade of the myocardial expression of
      several antioxidant genes. Overexpression of Nrf2 dramatically inhibited
      hypertrophic factor-induced ROS production and growth in both cardiomyocytes and
      cardiac fibroblasts, whereas knockdown of Nrf2 exerted opposite effects in both
      cells. CONCLUSIONS: These findings demonstrate that activation of Nrf2 provides a
      novel mechanism to protect the murine heart against pathological cardiac
      hypertrophy and heart failure via suppressing oxidative stress.

PMID- 19592469
TI  - Osteoprotegerin promotes fibrous cap formation in atherosclerotic lesions of ApoE
      deficient mice--brief report.
AB  - OBJECTIVE: Osteoprotegerin (OPG) is a tumor necrosis factor receptor-related
      cytokine, initially found to inhibit osteoclastogenesis. In the present study we
      investigated the effect of OPG treatment on atherosclerosis. METHODS AND RESULTS:
      Hypercholesterolemic apoe(-/-) mice were treated with recombinant 15 mg/kg OPG or
      vehicle injections twice a week for 10 consecutive weeks. Mice treated with OPG
      showed increased amounts of smooth muscle cells and collagen within the
      atherosclerotic lesions. OPG treatment did not affect atherosclerotic lesion size
      (8.2% versus 7.6%) or total vessel area but led to a 250% increase in lesion
      collagen, formation of mature collagen fibers in subendothelial fibrous caps, and
      upregulated mRNA for lysyl oxidase that promotes collagen crosslinking. In cell
      culture studies, OPG promoted cell proliferation in rat aortic smooth muscle
      cells. In contrast, OPG treatment did not affect markers of vascular or systemic
      inflammation. CONCLUSIONS: OPG treatment promotes smooth muscle accumulation,
      collagen fiber formation, and development of fibrous caps but does not affect
      inflammatory properties of atherosclerotic lesions. Its effects may contribute to
      plaque stabilization.

PMID- 19592471
TI  - Sphingosine 1-phosphate: a regulator of arterial lesions.
AB  - Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid that is critical in the
      development of blood vessels, and in the adult regulates vascular functions
      including vascular tone, endothelial integrity, and angiogenesis. Further, S1P
      may regulate arterial lesions in disease and after injury by controlling
      leukocyte recruitment and smooth muscle cell functions.

PMID- 19592472
TI  - Impending paradoxical embolism: systematic review of prognostic factors and
      treatment.
AB  - BACKGROUND: Little is known about the optimal management of impending paradoxical
      embolism (IPDE), a biatrial thromboembolus caught in transit across a patent
      foramen ovale. Our aim was to review observational studies on this subject to
      identify prognostic factors and to compare mortality and systemic embolism
      between treatments. METHODS: Systematic literature searches in Medline, Embase,
      and Cochrane Library identified 154 studies (174 patients). The primary end point
      was 30-day mortality. The secondary end point was systemic embolism during
      treatment. RESULTS: Thirty-day mortality was 18.4%. On univariate analysis, age
      (64+/-13.9 vs 56.7+/-16.5; P = .01), coma (12.9% vs 2.2%; P = .02), and systemic
      embolism (71.9% vs 51.4%; P = .048) at presentation were significantly increased
      among nonsurvivors. Surgical thromboembolectomy had lower mortality than other
      treatment groups (10.6%; P = .04). In multivariable models, no prognostic factor
      was a significant independent predictor of mortality. Surgically treated patients
      had nonsignificantly reduced mortality (odds ratio [OR], 0.65 [0.24-1.72]; P =
      .65) and thrombolysis-treated patients had increased mortality (OR, 1.62 [0.43
      5.97]; P = .47). However, systemic embolism during treatment and combined
      mortality and systemic embolism was decreased in the surgery group (OR, 0.13
      [0.03-0.67]; P = .02 and OR, 0.26 [0.11-0.60]; P = .001). CONCLUSIONS: This
      review attempts to help guide what to do in IPDE, despite severe limitations of
      the methods. Surgical thromboembolectomy showed a nonsignificant trend toward
      improved survival, significantly reduced systemic embolism, and composite of
      mortality and systemic embolism, compared with anticoagulation alone.
      Thrombolysis, on the other hand, had the opposite effect, although not
      significantly.

PMID- 19592470
TI  - Tissue factor in coagulation: Which? Where? When?
AB  - Tissue factor (TF) is an integral membrane protein, normally separated from the
      blood by the vascular endothelium, which plays a key role in the initiation of
      blood coagulation. With a perforating vascular injury, TF becomes exposed to
      blood and binds plasma factor VIIa. The resulting complex initiates a series of
      enzymatic reactions leading to clot formation and vascular sealing. In some
      pathological states, circulating blood cells express TF as a result of exposure
      to an inflammatory stimulus leading to intravascular clotting, vessel occlusion,
      and thrombotic pathology. Numerous controversies have arisen related to the
      influence of structural features of TF, its presentation, and its function. There
      are contradictory reports about the synthesis and presentation of TF on blood
      cells and the presence (or absence) of functionally active TF circulating in
      normal blood either on microparticles or as a soluble protein. In this review we
      discuss TF structure-function relationships and the role of TF during various
      phases of the blood coagulation process. We also highlight controversies
      concerning the expression/presence of TF on various cells and in blood in normal
      and pathological states.

PMID- 19592473
TI  - Obesity-asthma association: is it explained by systemic oxidant stress?
AB  - BACKGROUND: The mechanism for the obesity-asthma association is unknown. This
      study evaluated the hypothesis that systemic oxidant stress explains this
      association. METHODS: This cross-sectional study used year-20 follow-up
      evaluation data of 2,865 eligible participants in the Coronary Artery Risk
      Development in Young Adults (CARDIA) cohort. Current asthma was self-reported.
      Oxidant stress primarily was assessed by plasma F2-isoprostane concentrations.
      Obesity measures included categories of BMI and dual-energy x-ray absorptiometry
      assessed fat mass index (FMI) and lean mass index (LMI). Logistic and linear
      regressions were used for analyses. RESULTS: Asthma was associated with higher
      plasma F2-isoprostane concentrations (p = 0.049); however, this association was
      not significant when adjusted for either gender or BMI. The BMI-asthma
      association was seen only among women (p = 0.03; gender-specific interaction, p =
      0.01), and this association was not explained by plasma F2-isoprostane levels.
      Similarly, both FMI and LMI were positively associated with asthma in women (p =
      0.20 and 0.01, respectively). These associations also were not explained by
      plasma F2-isoprostane levels. Similar results were obtained when plasma levels of
      oxidized low-density lipoprotein were used instead of F2-isoprostane levels to
      study the BMI-asthma association at the year-15 evaluation. CONCLUSIONS: Systemic
      oxidant stress, primarily assessed by plasma F2-isoprostane concentrations, was
      not independently associated with asthma and, therefore, may not explain the
      obesity-asthma association in women. The asthma-oxidant stress association is
      confounded by gender and obesity. This study is limited by the inability to
      measure airway oxidant stress. It is possible that another (as yet undetermined)
      measure of systemic oxidant stress may be more relevant in asthma.

PMID- 19592474
TI  - Factors that predict risk of thrombosis in relatives of patients with unprovoked
      venous thromboembolism.
AB  - BACKGROUND: Factors that predict the risk of venous thromboembolism in the first
      degree relatives of patients with unprovoked venous thromboembolism are uncertain
      but important for counseling. We aimed to identify risk factors for, and quantify
      the risk of, venous thromboembolism in first-degree relatives of patients (index
      case patients) with a first episode of unprovoked venous thromboembolism.
      METHODS: In a cross-sectional study, using a standardized method and without
      knowledge of whether patients or their relatives had thrombophilia, we assessed
      the prevalence of previous venous thromboembolism in 1,916 first-degree relatives
      of 378 unselected patients with a first episode of unprovoked venous
      thromboembolism. Patient characteristics, and the presence of factor V Leiden or
      the G20210A prothrombin gene mutation in patients, were assessed as predictors of
      venous thromboembolism in patient's relatives. RESULTS: There were 102 previous
      episodes of venous thromboembolism in the first-degree relatives (prevalence,
      5.3%). Thrombosis at a young age in patients was the strongest predictor of
      venous thromboembolism in relatives, with an adjusted odds ratio (OR) for younger
      patients (ie, patients < 45 years of age when venous thromboembolism occurred;
      lowest quartile) compared with older patients (ie, patients > 71 years of age;
      highest quartile) of 3.27 (95% CI, 1.68 to 6.38). The presence of factor V Leiden
      or the G20210A prothrombin gene in patients was a weak independent predictor of
      venous thromboembolism in relatives (adjusted OR, 1.48; 95% CI, 0.94 to 2.33).
      CONCLUSION: Unprovoked venous thromboembolism at a young age is associated with a
      substantially increased risk of venous thromboembolism in patients' families.

PMID- 19592475
TI  - Cardiovascular safety of tiotropium in patients with COPD.
AB  - BACKGROUND: The clinical trial safety database for tiotropium has been augmented
      with a 4-year trial in patients with COPD, which provides an opportunity to
      better evaluate the cardiovascular (CV) profile of tiotropium. METHODS: Trials
      with the following criteria were considered: > or = 4 weeks, randomized, double
      blind, parallel-group, placebo-controlled. Inclusion/exclusion criteria were
      similar, including spirometry-confirmed COPD, > or = 10 pack-year smoking, and
      age > or = 40 years. Adverse events were collected throughout each trial using
      standardized case report forms. Incidence rates (IRs) were determined from the
      total number of patients with an event divided by total time at risk. Rate ratios
      (RRs) and 95% CI for tiotropium/placebo were calculated. IRs were determined for
      all-cause mortality and selected CV events, including a composite CV end point
      encompassing CV deaths, nonfatal myocardial infarction (MI), nonfatal stroke, and
      the terms sudden death, sudden cardiac death, and cardiac death. RESULTS: There
      were 19,545 patients randomized: 10,846 (tiotropium) and 8,699 (placebo) from 30
      trials. Mean FEV(1) = 1.15 +/- 0.46 L (41 +/- 14% predicted), 76% men, mean age =
      65 +/- 9 years. Cumulative exposure to study drug was 13,146 (tiotropium) and
      11,095 (placebo) patient-years. For all-cause mortality, the IR was 3.44
      (tiotropium) and 4.10 (placebo) per 100 patient-years (RR [95% CI] = 0.88 [0.77
      0.999]). IR for the CV end point was 2.15 (tiotropium) and 2.67 (placebo) per 100
      patient-years (RR [95% CI] = 0.83 (0.71-0.98]). The IR for the CV mortality
      excluding nonfatal MI and stroke was 0.91 (tiotropium) and 1.24 (placebo) per 100
      patient-years (RR [95% CI] = 0.77 [0.60-0.98]). For total MI, cardiac failure,
      and stroke the RRs (95% CI) were 0.78 (0.59-1.02), 0.82 (0.69-0.98), and 1.03
      (0.79-1.35), respectively. CONCLUSION: Tiotropium was associated with a reduction
      in the risk of all-cause mortality, CV mortality, and CV events.

PMID- 19592476
TI  - Ethanol extract of fructus schisandrae decreases hepatic triglyceride level in
      mice fed with a high fat/cholesterol diet, with attention to acute toxicity.
AB  - Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver
      lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet
      for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused
      significant increases in serum and hepatic total cholesterol (TC) levels (up to
      62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice.
      EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14,
      i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly
      increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas
      fenofibrate treatment (0.1 g/kg/day for 7 days, i.g.) significantly lowered the
      hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in
      hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively
      non-toxic, with an LD(50) value of 35.63 +/- 6.46 g/kg in mice. The results
      indicate that EtFSC treatment can invariably decrease hepatic TG in
      hypercholesterolemic mice, as assessed by both preventive and therapeutic
      protocols, suggesting its potential use for fatty liver treatment.

PMID- 19592478
TI  - Investigation of electroacupuncture and manual acupuncture on carnitine and
      glutathione in muscle.
AB  - Electroacupuncture (EA) and manual acupuncture (MA) have therapeutic effects on
      muscle fatigue in muscle disease. The deficiencies of carnitine and glutathione
      induce muscle fatigue. This report investigated the effects of EA and MA on
      carnitine and glutathione in muscle. After the mice of EA group were fixed in the
      animal cage, right Zusanli (ST36) and Jiexi (ST41) were acupunctured and
      stimulated with uniform reinforcing and reducing method by twirling the
      acupuncture needle for 15 min. And then, the needle handles were connected to an
      electric stimulator for stimulating the acupoint with dense-sparse waves. After
      the mice of MA group were fixed in an animal cage, right ST36 and ST41 were
      acupunctured and allowed for 15 min. The mice of normal control group were not
      acupunctured and stimulated for 15 min. The mice of all groups were killed for
      collecting muscle tissue 1 h after the final treatment. Carnitine and glutathione
      in homogenate of muscle tissue were determined with carnitine (Kainos
      Laboratories Co., Tokyo, Japan) and glutathione assay kit (Dojin Chemicals Co.,
      Kumamoto, Japan). Carnitine level in muscle tissue of MA group was significantly
      higher than those of EA group and normal control group. Carnitine level in muscle
      tissue of EA group was not significantly different from that of normal control
      group. Glutathione levels in muscle tissue of EA group and MA group were
      significantly higher than that of normal control group. This report presented
      that carnitine in muscle is increased by MA, and not increased by EA, and that
      glutathione in muscle is increased by EA and MA.

PMID- 19592477
TI  - 8-Prenylkaempferol Suppresses Influenza A Virus-Induced RANTES Production in A549
      Cells via Blocking PI3K-Mediated Transcriptional Activation of NF-kappaB and
      IRF3.
AB  - 8-Prenylkaempferol (8-PK) is a prenylflavonoid isolated from Sophora flavescens,
      a Chinese herb with antiviral and anti-inflammatory properties. In this study, we
      investigated its effect on regulated activation, normal T cell expressed and
      secreted (RANTES) secretion by influenza A virus (H1N1)-infected A549 alveolar
      epithelial cells. Cell inoculation with H1N1 evoked a significant induction in
      RANTES accumulation accompanied with time-related increase in nuclear
      translocation of nuclear factor-kappaB (NF-kappaB) and interferon regulatory
      factor 3 (IRF-3), but showed no effect on c-Jun phosphorylation. 8-PK could
      significantly inhibit not only RANTES production but also NF-kappaB and IRF-3
      nuclear translocation. We had proved that both NF-kappaB and IRF-3 participated
      in H1N1-induced RANTES production since NF-kappaB inhibitor pyrrolidinedithio
      carbamate (PDTC) and IRF-3 siRNA attenuated significantly RANTES accumulation.
      H1N1 inoculation also increased PI3K activity as well as Akt phosphorylation and
      such responsiveness were attenuated by 8-PK. In the presence of wortmannin,
      nuclear translocation of NF-kappaB and IRF3 as well as RANTES production by H1N1
      infection were all reversed, demonstrating that PI3K-Akt pathway is essential for
      NF-kappaB- and IRF-3-mediated RANTES production in A549 cells. Furthermore, 8-PK
      but not wortmannin, prevented effectively H1N1-evoked IkappaB degradation. In
      conclusion, 8-PK might be an anti-inflammatory agent for suppressing influenza A
      virus-induced RANTES production acts by blocking PI3K-mediated transcriptional
      activation of NF-kappaB and IRF-3 and in part by interfering with IkappaB
      degradation which subsequently decreases NF-kappaB translocation.

PMID- 19592479
TI  - North American (Panax quinquefolius) and Asian Ginseng (Panax ginseng)
      Preparations for Prevention of the Common Cold in Healthy Adults: A Systematic
      Review.
AB  - BACKGROUND: Standardized ginseng extract has become the best-selling cold and flu
      remedy in Canada, yet much controversy regarding the efficacy of ginseng in
      preventing common colds remains. OBJECTIVE: To assess the efficacy of ginseng
      preparations for the prevention of common colds in healthy adults. METHODS:
      Comprehensive bibliographic database, trial registry and grey literature searches
      were conducted up to December 2007. Randomized controlled trials or controlled
      clinical trials comparing North American (Panax quinquefolius) or Asian ginseng
      (Panax ginseng) root extract to placebo or no treatment in healthy adults were
      included. Two reviewers independently applied the study selection criteria and
      assessed methodological quality. RESULTS: Five trials involving 747 participants
      were included. All five trials examined North American ginseng. The
      methodological quality of the trials varied widely. Ginseng preparations
      significantly reduced the total number of common colds by 25% compared to placebo
      (one trial; 95% CI: 5-45). There was a tendency toward a lower incidence of
      having at least one common cold or other acute respiratory infection (ARI) in the
      ginseng group compared to the placebo group (five trials; relative risk: 0.70;
      95% CI: 0.48-1.02). Compared to placebo, ginseng significantly shortened the
      duration of colds or ARIs by 6.2 days (two trials; 95% CI: 3.4-9.0). CONCLUSIONS:
      There is insufficient evidence to conclude that ginseng reduces the incidence or
      severity of common colds. North American ginseng appears to be effective in
      shortening the duration of colds or ARIs in healthy adults when taken
      preventatively for durations of 8-16 weeks.

PMID- 19592480
TI  - Intestinal Anti-Inflammatory Activity of Baccharis dracunculifolia in the
      Trinitrobenzenesulphonic Acid Model of Rat Colitis.
AB  - Baccharis dracunculifolia DC (Asteraceae) is a Brazilian medicinal plant
      popularly used for its antiulcer and anti-inflammatory properties. This plant is
      the main botanical source of Brazilian green propolis, a natural product
      incorporated into food and beverages to improve health. The present study aimed
      to investigate the chemical profile and intestinal anti-inflammatory activity of
      B. dracunculifolia extract on experimental ulcerative colitis induced by
      trinitrobenzenosulfonic acid (TNBS). Colonic damage was evaluated macroscopically
      and biochemically through its evaluation of glutathione content and its
      myeloperoxidase (MPO) and alkaline phosphatase activities. Additional in vitro
      experiments were performed in order to test the antioxidant activity by
      inhibition of induced lipid peroxidation in the rat brain membrane. Phytochemical
      analysis was performed by HPLC using authentic standards. The administration of
      plant extract (5 and 50 mg kg(-1)) significantly attenuated the colonic damage
      induced by TNBS as evidenced both macroscopically and biochemically. This
      beneficial effect can be associated with an improvement in the colonic oxidative
      status, since plant extract prevented glutathione depletion, inhibited lipid
      peroxidation and reduced MPO activity. Caffeic acid, p-coumaric acid,
      aromadendrin-4-O-methyl ether, 3-prenyl-p-coumaric acid, 3,5-diprenyl-p-coumaric
      acid and baccharin were detected in the plant extract.

PMID- 19592481
TI  - Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis
      in ASTC-a-1 Cells.
AB  - Bufalin has been shown to induce cancer cell death through apoptotic pathways.
      However, the molecular mechanisms are not well understood. In this study, we used
      the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal
      dynamics of reactive oxygen species (ROS) production, Bax translocation and
      caspase-3 activation during bufalin-induced apoptosis in living human lung
      adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic
      cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry
      analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after
      bufalin treatment in living cells expressed with green fluorescent protein Bax.
      Treatment with the antioxidant N-acetyl-cysteine (NAC), a ROS scavenger,
      inhibited ROS generation and Bax translocation and led to a significant
      protection against bufalin-induced apoptosis. Our results also revealed that
      bufalin induced a prominent increase of caspase-3 activation blocked potently by
      NAC. Taken together, bufalin induced ROS-mediated Bax translocation,
      mitochondrial permeability transition and caspase-3 activation, implying that
      bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a
      1 cells.

PMID- 19592482
TI  - RazerS--fast read mapping with sensitivity control.
AB  - Second-generation sequencing technologies deliver DNA sequence data at
      unprecedented high throughput. Common to most biological applications is a
      mapping of the reads to an almost identical or highly similar reference genome.
      Due to the large amounts of data, efficient algorithms and implementations are
      crucial for this task. We present an efficient read mapping tool called RazerS.
      It allows the user to align sequencing reads of arbitrary length using either the
      Hamming distance or the edit distance. Our tool can work either lossless or with
      a user-defined loss rate at higher speeds. Given the loss rate, we present an
      approach that guarantees not to lose more reads than specified. This enables the
      user to adapt to the problem at hand and provides a seamless tradeoff between
      sensitivity and running time.

PMID- 19592483
TI  - FINHYST 2006--national prospective 1-year survey of 5,279 hysterectomies.
AB  - BACKGROUND: In Finland, the number of hysterectomies during one decade has
      decreased by 34%. The national prospective FINHYST study in 1996 showed abdominal
      hysterectomy (AH) as being most common: 58%. In Finland since 2002, vaginal
      hysterectomy (VH) has been most preferred, with laparoscopic hysterectomy (LH)
      surpassing AH in 2005. METHODS: FINHYST 2006 is a national prospective
      hysterectomy study in which all hospitals collaborated from 1 January to 31
      December 2006. Questionnaires, completed by gynaecologists, covered their
      experience, patient characteristics and surgical data. RESULTS: The 5279
      hysterectomies distributed by approaches were 44% VHs, 32% LHs and 24% AHs. Less
      than 2% were subtotal. The main indications for hysterectomy were myomas (33%),
      uterine prolapse (28%) and menorrhagia (21%). The main indication for VH was not
      related to uterine prolapse in 39%. Bilateral salpingo-ooforectomy was performed
      in 36% of AHs, 32% of LHs and 2% of VHs. Antibiotic prophylaxis was used in 97%,
      and thrombosis prophylaxis in 65%. Haemorrhage was least and operation time
      shortest with VH, and hospital stay and sick leave were shortest after LH.
      CONCLUSIONS: In Finland, less invasive approaches comprise 76% of hysterectomies.
      This trend has resulted nationally in shortening of hospital stay and of
      convalescence time.

PMID- 19592484
TI  - A constitutive model for smooth muscle including active tone and passive
      viscoelastic behaviour.
AB  - A new constitutive model for the biomechanical behaviour of smooth muscle tissue
      is proposed. The active muscle contraction is accomplished by the relative
      sliding between actin and myosin filaments, comprising contractile units in the
      smooth muscle cells. The model includes a chemical part, governing the cross
      bridge (myosin head) cycling, that is responsible for the filament sliding. The
      number of activated cross-bridges govern the contractile force generated and also
      the contraction speed. A strain-energy function is used to describe the
      mechanical behaviour of the smooth muscle tissue. Besides the active contractile
      apparatus, the mechanical model also incorporates a passive viscoelastic part.
      The constitutive model was calibrated with respect to experiments on smooth
      muscle tissue from swine carotid artery and guinea pig taenia coli, in terms of
      isometric and isotonic tensile test results. The model was fully able to
      reproduce the experimental results.

PMID- 19592485
TI  - cAMP stimulates apical exocytosis of the renal Na(+)-K(+)-2Cl(-) cotransporter
      NKCC2 in the thick ascending limb: role of protein kinase A.
AB  - The apical renal Na(+)-K(+)-2Cl(-) cotransporter NKCC2 mediates NaCl absorption
      by the thick ascending limb (TAL) of Henle's loop. cAMP stimulates NKCC2 by
      enhancing steady-state apical membrane levels of this protein; however, the
      trafficking and signaling mechanisms by which this occurs have not been studied.
      Here, we report that stimulation of endogenous cAMP levels with either
      forskolin/3-isobutyl-1-methylxanthine (IBMX) or the V2 receptor agonist [deamino
      Cys(1),d-Arg(8)]vasopressin increases steady-state surface NKCC2 and that the
      protein kinase A (PKA) inhibitor H-89 blocks this effect. Confocal imaging of
      apical surface NKCC2 in isolated perfused TALs confirmed a stimulatory effect of
      cAMP on apical trafficking that was blocked by PKA inhibition. Selective
      stimulation of PKA with the agonist N(6)-benzoyl-cAMP (500 microm) stimulated
      steady-state surface NKCC2, whereas the Epac-selective agonist 8-p
      chlorophenylthio-2'-O-methyl-cAMP (100 and 250 microm) had no effect. To explore
      the trafficking mechanism by which cAMP increases apical NKCC2, we measured
      cumulative apical membrane exocytosis and NKCC2 exocytic insertion in TALs. By
      monitoring apical FM1-43 fluorescence, we observed rapid stimulation of apical
      exocytosis (2 min) by forskolin/IBMX. We also found constitutive exocytic
      insertion of NKCC2 in TALs over time, which was increased by 3-fold in the
      presence of forskolin/IBMX. PKA inhibition blunted cAMP-stimulated exocytic
      insertion but did not affect the rate of constitutive exocytosis. We conclude
      that cAMP stimulates steady-state apical surface NKCC2 by stimulating exocytic
      insertion and that this process is highly dependent on PKA but not Epac.

PMID- 19592486
TI  - Synthesis, solution structure, and phylum selectivity of a spider delta-toxin
      that slows inactivation of specific voltage-gated sodium channel subtypes.
AB  - Magi 4, now renamed delta-hexatoxin-Mg1a, is a 43-residue neurotoxic peptide from
      the venom of the hexathelid Japanese funnel-web spider (Macrothele gigas) with
      homology to delta-hexatoxins from Australian funnel-web spiders. It binds with
      high affinity to receptor site 3 on insect voltage-gated sodium (Na(V)) channels
      but, unlike delta-hexatoxins, does not compete for the related site 3 in rat
      brain despite being previously shown to be lethal by intracranial injection. To
      elucidate differences in Na(V) channel selectivity, we have undertaken the first
      characterization of a peptide toxin on a broad range of mammalian and insect
      Na(V) channel subtypes showing that delta-hexatoxin-Mg1a selectively slows
      channel inactivation of mammalian Na(V)1.1, Na(V)1.3, and Na(V)1.6 but more
      importantly shows higher affinity for insect Na(V)1 (para) channels.
      Consequently, delta-hexatoxin-Mg1a induces tonic repetitive firing of nerve
      impulses in insect neurons accompanied by plateau potentials. In addition, we
      have chemically synthesized and folded delta-hexatoxin-Mg1a, ascertained the
      bonding pattern of the four disulfides, and determined its three-dimensional
      solution structure using NMR spectroscopy. Despite modest sequence homology, we
      show that key residues important for the activity of scorpion alpha-toxins and
      delta-hexatoxins are distributed in a topologically similar manner in delta
      hexatoxin-Mg1a. However, subtle differences in the toxin surfaces are important
      for the novel selectivity of delta-hexatoxin-Mg1a for certain mammalian and
      insect Na(V) channel subtypes. As such, delta-hexatoxin-Mg1a provides us with a
      specific tool with which to study channel structure and function and determinants
      for phylum- and tissue-specific activity.

PMID- 19592487
TI  - Role of Schlafen 2 (SLFN2) in the generation of interferon alpha-induced growth
      inhibitory responses.
AB  - The precise STAT-regulated gene targets that inhibit cell growth and generate the
      antitumor effects of Type I interferons (IFNs) remain unknown. We provide
      evidence that Type I IFNs regulate expression of Schlafens (SLFNs), a group of
      genes involved in the control of cell cycle progression and growth inhibitory
      responses. Using cells with targeted disruption of different STAT proteins and/or
      the p38 MAP kinase, we demonstrate that the IFN-dependent expression of distinct
      Schlafen genes is differentially regulated by STAT complexes and the p38 MAP
      kinase pathway. We also provide evidence for a key functional role of a member of
      the SLFN family, SLFN2, in the induction of the growth-suppressive effects of
      IFNs. This is shown in studies demonstrating that knockdown of SLFN2 enhances
      hematopoietic progenitor colony formation and reverses the growth-suppressive
      effects of IFNalpha on normal hematopoietic progenitors. Importantly, NIH3T3 or
      L929 cells with stable knockdown of SLFN2 form more colonies in soft agar,
      implicating this protein in the regulation of anchorage-independent growth.
      Altogether, our data implicate SLFN2 as a negative regulator of the metastatic
      and growth potential of malignant cells and strongly suggest a role for the SLFN
      family of proteins in the generation of the antiproliferative effects of Type I
      IFNs.

PMID- 19592488
TI  - NDRG4 is required for cell cycle progression and survival in glioblastoma cells.
AB  - NDRG4 is a largely unstudied member of the predominantly tumor suppressive N-Myc
      downstream-regulated gene (NDRG) family. Unlike its family members NDRG1-3, which
      are ubiquitously expressed, NDRG4 is expressed almost exclusively in the heart
      and brain. Given this tissue-specific expression pattern and the established
      tumor suppressive roles of the NDRG family in regulating cellular proliferation,
      we investigated the cellular and biochemical functions of NDRG4 in the context of
      astrocytes and glioblastoma multiforme (GBM) cells. We show that, in contrast to
      NDRG2, NDRG4 expression is elevated in GBM and NDRG4 is required for the
      viability of primary astrocytes, established GBM cell lines, and both CD133(+)
      (cancer stem cell (CSC)-enriched) and CD133(-) primary GBM xenograft cells. While
      NDRG4 overexpression has no effect on cell viability, NDRG4 knockdown causes G(1)
      cell cycle arrest followed by apoptosis. The initial G(1) arrest is associated
      with a decrease in cyclin D1 expression and an increase in p27(Kip1) expression,
      and the subsequent apoptosis is associated with a decrease in the expression of
      XIAP and survivin. As a result of these effects on cell cycle progression and
      survival, NDRG4 knockdown decreases the tumorigenic capacity of established GBM
      cell lines and GBM CSC-enriched cells that have been implanted intracranially
      into immunocompromised mice. Collectively, these data indicate that NDRG4 is
      required for cell cycle progression and survival, thereby diverging in function
      from its tumor suppressive family member NDRG2 in astrocytes and GBM cells.

PMID- 19592489
TI  - AP-1 activated by toll-like receptors regulates expression of IL-23 p19.
AB  - Interleukin (IL)-23, a new member of the IL-12 family, plays a central role in
      the Th17 immune response and in autoimmune diseases. It is clear that activated
      macrophages and dendritic cells produce IL-23, but the molecular mechanisms
      whereby inflammatory signals stimulate IL-23 expression are not fully understood.
      We demonstrate that induction of IL-23 p19 gene expression by LPS depends on the
      TLR4 and MyD88 pathways. All three MAPK pathways (ERK, JNK, and p38) that are
      activated by lipopolysaccharide (LPS) stimulation were shown to exert a positive
      effect on p19 expression. We cloned a 1.3-kb putative p19 promoter and defined
      its transcription initiation sites by the 5'-rapid amplification of cDNA ends
      method. By analyzing IL-23 p19 promoter mutants, we have identified a promoter
      region (-413 to +10) that contains several important elements, including NF
      kappaB and AP-1. In addition to NF-kappaB, we have demonstrated that the proximal
      AP-1 site is important for p19 promoter activation. Mutation of the AP-1 site
      resulted in the loss of p19 promoter activation. Electrophoretic mobility shift
      assay (EMSA) analysis showed that c-Jun and c-Fos bind to the AP-1 site, which
      was confirmed by a chromatin immunoprecipitation assay. Furthermore, co
      transfection of c-Jun and ATF2 synergistically induced p19 promoter activation,
      and c-Jun and ATF2 formed a protein complex, demonstrated by co
      immunoprecipitation. Finally, LPS-stimulated peritoneal macrophages from IL-10
      deficient mice expressed significantly higher IL-23 p19 than macrophages from
      wild type mice, and the addition of recombinant IL-10 strongly inhibited LPS
      induced p19 expression. Thus, this study suggests that MyD88-dependent Toll-like
      receptor signaling induces IL-23 p19 gene expression through both MAPKs and NF
      kappaB.

PMID- 19592490
TI  - Synergistic induction of endothelin-1 by tumor necrosis factor alpha and
      interferon gamma is due to enhanced NF-kappaB binding and histone acetylation at
      specific kappaB sites.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor and co-mitogen for vascular
      smooth muscle and is implicated in pulmonary vascular remodeling and the
      development of pulmonary arterial hypertension. Vascular smooth muscle is an
      important source of ET-1. Here we demonstrate synergistic induction of preproET-1
      message RNA and release of mature peptide by a combination of tumor necrosis
      factor alpha (TNFalpha) and interferon gamma (IFNgamma) in primary human
      pulmonary artery smooth muscle cells. This induction was prevented by
      pretreatment with the histone acetyltransferase inhibitor anacardic acid.
      TNFalpha induced a rapid and prolonged pattern of nuclear factor (NF)-kappaB p65
      subunit activation and binding to the native preproET-1 promoter. In contrast,
      IFNgamma induced a delayed activation of interferon regulatory factor-1 without
      any effect on NF-kappaB p65 nuclear localization or consensus DNA binding.
      However, we found cooperative p65 binding and histone H4 acetylation at distinct
      kappaB sites in the preproET-1 promoter after stimulation with both TNFalpha and
      IFNgamma. This was associated with enhanced recruitment of RNA polymerase II to
      the ATG start site and read-through of the ET-1 coding region. Understanding such
      mechanisms is crucial in determining the key control points in ET-1 release. This
      has particular relevance to developing novel treatments targeted at the
      inflammatory component of pulmonary vascular remodeling.

PMID- 19592491
TI  - Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell
      death in neurons.
AB  - Terminally differentiated neurons are unable to reenter the cell cycle. Aberrant
      cell cycle activation provokes neuronal cell death, whereas cell cycle inhibition
      elevates neuronal survival. However, the molecular mechanism regulating the cell
      cycle and cell death in mature neurons remains elusive. Here we show that SRPK2,
      a protein kinase specific for the serine/arginine (SR) family of splicing
      factors, triggers cell cycle progression in neurons and induces apoptosis through
      regulation of nuclear cyclin D1. Akt phosphorylates SRPK2 on Thr-492 and promotes
      its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry,
      and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus,
      inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2,
      regulated by Akt phosphorylation, inhibits these events. We find that SRPK2 is
      phosphorylated in ischemia-attacked brain, correlating with the observed increase
      in cyclin D1 levels. Hence, phosphatidylinositol 3-kinase/Akt mediates the cell
      cycle and cell death machinery in the nervous system through phosphorylation of
      SRPK2.

PMID- 19592492
TI  - Increased cytokine production in interleukin-18 receptor alpha-deficient cells is
      associated with dysregulation of suppressors of cytokine signaling.
AB  - Since interleukin (IL)-18 is a proinflammatory cytokine, mice lacking IL-18 or
      its ligand-binding receptor (IL-18R) should exhibit decreased cytokine and
      chemokine production. Indeed, production of IL-1alpha, IL-6, and MIP-1alpha was
      reduced in IL-18 knock-out (ko) mouse embryonic fibroblast (MEF)-like cells.
      Unexpectedly, we observed a paradoxical 10-fold increase in IL-1beta-induced IL-6
      production in MEF cells from mice deficient in the IL-18R alpha-chain (IL
      18Ralpha) compared with wild type MEF. Similar increases were observed for IL
      1alpha, MIP-1alpha, and prostaglandin E2. Likewise, coincubation with a specific
      IL-18Ralpha-blocking antibody augmented IL-1beta-induced cytokines in wild type
      and IL-18 ko MEF. Stable lines of IL-18Ralpha-depleted human A549 cells were
      generated using shRNA, resulting in an increase of IL-1beta-induced IL-1alpha, IL
      6, and IL-8 compared to scrambled small hairpin RNA. In addition, we silenced IL
      18Ralpha with small interfering RNA in primary human blood cells and observed up
      to 4-fold increases in the secretion of lipopolysaccharide- and IL-12/IL-18
      induced IL-1beta, IL-6, interferon-gamma, and CD40L. Mechanistically, despite
      increases in Stat1 and IL-6, induction of SOCS1 and -3 (suppressor of cytokine
      signaling 1 and 3) was markedly reduced in the absence of IL-18Ralpha. Consistent
      with these observations, activation of the p38alpha/beta and ERK1/2 MAPKs and of
      protein kinase B/Akt increased in IL-18Ralpha ko MEF, whereas the negative
      feedback kinase MSK2 was more active in IL-18 ko cells. These data reveal a role
      for SOCS1 and -3 in the seemingly paradoxical hyperresponsive state in cells
      deficient in IL-18Ralpha, supporting the concept that IL-18Ralpha participates in
      both pro- and anti-inflammatory responses and that an endogenous ligand engages
      IL-18Ralpha to deliver an inhibitory signal.

PMID- 19592493
TI  - An oligomeric signaling platform formed by the Toll-like receptor signal
      transducers MyD88 and IRAK-4.
AB  - Toll-like receptors (TLRs) mediate responses to pathogen-associated molecules as
      part of the vertebrate innate immune response to infection. Receptor dimerization
      is coupled to downstream signal transduction by the recruitment of a post
      receptor complex containing the adaptor protein MyD88 and the IRAK protein
      kinases. In this work, we show that the death domains of human MyD88 and IRAK-4
      assemble into closed complexes having unusual stoichiometries of 7:4 and 8:4, the
      Myddosome. Formation of the Myddosome is likely to be a key event for TLR4
      signaling in vivo as we show here that pathway activation requires that the
      receptors cluster into lipid rafts. Taken together, these findings indicate that
      TLR activation causes the formation of a highly oligomeric signaling platform
      analogous to the death-inducing signaling complex of the Fas receptor pathway.

PMID- 19592494
TI  - No specific subcellular localization of protein kinase C is required for
      cytotoxic T cell granule exocytosis.
AB  - Cytotoxic T cells kill virus-infected cells and tumor cells by releasing lytic
      granules that contain cell-killing contents. Exocytosis requires calcium influx
      and protein kinase C (PKC) activation. Here, we extend our previous finding
      regarding the lack of isoform specificity of PKCs in the granule release step,
      showing that mutant constitutively active PKCdelta can substitute for phorbol
      esters and support exocytosis. PKCdelta, a novel PKC isoform, was recently shown
      to play a role in lytic granule reorientation. Surprisingly, however, our results
      suggested that mutant PKCdelta did not localize to the plasma membrane (PM). To
      test directly whether PKC has to be in the PM to drive exocytosis, we generated
      mutants of various PKC isoforms that were tethered either to the outer
      mitochondrial membrane or to the PM. Tethered mutant PKCdeltas were able to
      promote exocytosis as effectively as the untethered version. The substrates of
      PKCs involved in lytic granule exocytosis are currently unknown, but subcellular
      localization is believed to be a critical factor in determining PKC accessibility
      to substrates. That there is no requirement for specific PKC localization in
      lytic granule exocytosis may have important implications for the identity of PKC
      substrates.

PMID- 19592496
TI  - A monomeric chicken IgY receptor binds IgY with 2:1 stoichiometry.
AB  - IgY is the principal serum antibody in birds and reptiles, and an IgY-like
      molecule was the evolutionary precursor of both mammalian IgG and IgE. A receptor
      for IgY on chicken monocytes, chicken leukocyte receptor AB1 (CHIR-AB1), lies in
      the avian leukocyte receptor cluster rather than the classical Fc receptor
      cluster where the genes for mammalian IgE and IgG receptors are found. IgG and
      IgE receptors bind to the lower hinge region of their respective antibodies with
      1:1 stoichiometry, whereas the myeloid receptor for IgA, FcalphaRI, and the IgG
      homeostasis receptor, FcRn, which are found in the mammalian leukocyte receptor
      cluster, bind with 2:1 stoichiometry between the heavy chain constant domains 2
      and 3 of each heavy chain. In this paper, the extracellular domain of CHIR-AB1
      was expressed in a soluble form and shown to be a monomer that binds to IgY-Fc
      with 2:1 stoichiometry. The two binding sites have similar affinities: K(a)(1) =
      7.22 +/- 0.22 x 10(5) m(-1) and K(a)(2) = 3.63 +/- 1.03 x 10(6) m(-1) (comparable
      with the values reported for IgA binding to its receptor). The affinity constants
      for IgY and IgY-Fc binding to immobilized CHIR-AB1 are 9.07 +/- 0.07 x 10(7) and
      6.11 +/- 0.02 x 10(8) m(-1), respectively, in agreement with values obtained for
      IgY binding to chicken monocyte cells and comparable with reported values for
      human IgA binding to neutrophils. Although the binding site for CHIR-AB1 on IgY
      is not known, the data reported here with a monomeric receptor binding to IgY at
      two sites with low affinity suggest an IgA-like interaction.

PMID- 19592495
TI  - The structure of the Staphylococcus aureus sortase-substrate complex reveals how
      the universally conserved LPXTG sorting signal is recognized.
AB  - In Gram-positive bacteria, sortase enzymes assemble surface proteins and pili in
      the cell wall envelope. Sortases catalyze a transpeptidation reaction that joins
      a highly conserved LPXTG sorting signal within their polypeptide substrate to the
      cell wall or to other pilin subunits. The molecular basis of transpeptidation and
      sorting signal recognition are not well understood, because the intermediates of
      catalysis are short lived. We have overcome this problem by synthesizing an
      analog of the LPXTG signal whose stable covalent complex with the enzyme mimics a
      key thioacyl catalytic intermediate. Here we report the solution structure and
      dynamics of its covalent complex with the Staphylococcus aureus SrtA sortase. In
      marked contrast to a previously reported crystal structure, we show that SrtA
      adaptively recognizes the LPXTG sorting signal by closing and immobilizing an
      active site loop. We have also used chemical shift mapping experiments to
      localize the binding site for the triglycine portion of lipid II, the second
      substrate to which surface proteins are attached. We propose a unified model of
      the transpeptidation reaction that explains the functions of key active site
      residues. Since the sortase-catalyzed anchoring reaction is required for the
      virulence of a number of bacterial pathogens, the results presented here may
      facilitate the development of new anti-infective agents.

PMID- 19592497
TI  - MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and
      TLR4-mediated NF-kappaB proinflammatory responses.
AB  - Toll/interleukin-1 (TIR)receptor-containing adapters are critical in
      orchestrating the different signal transduction pathways following Toll-like
      receptor (TLR) activation. MyD88 adapter-like (Mal), also termed TIRAP, is
      involved in bridging MyD88 to the receptor complex for TLR-2 and TLR4 signaling
      in response to bacterial infection. We have previously reported an interaction
      between Mal and tumor necrosis factor receptor-associated factor 6 (TRAF6) via a
      TRAF6-binding motif, the disruption of which inhibited TLR-mediated NF-kappaB
      luciferase reporter activity. Given the recent report of intracellular TRAM
      localization promoting sequential signaling in TLR4 responses, we further
      characterized Mal interaction with TRAF6, the cellular localization, and the
      outcomes of disrupting this association on TLR inflammatory responses. We found
      that Mal and TRAF6 directly interact in response to TLR2 and TLR4 stimulation,
      although membrane localization is not necessary to facilitate interaction.
      Critically, reconstitution of murine Mal-deficient macrophages with MalE190A,
      containing a mutation within the TRAF6-binding motif, fails to reconstitute the
      proinflammatory response to TLR2 and TLR4 ligands compared with wild type Mal.
      Furthermore, Mal interaction with TRAF6 mediates Ser phosphorylation of the p65
      subunit of NF-kappaB and thus controls transcriptional activation but not nuclear
      translocation of NF-kappaB. This study characterizes the novel role for Mal in
      facilitating the direct recruitment of TRAF6 to the plasma membrane, which is
      necessary for TLR2- and TLR4-induced transactivation of NF-kappaB and regulation
      of the subsequent pro-inflammatory response.

PMID- 19592499
TI  - Cell polarity factor Par3 binds SPTLC1 and modulates monocyte serine
      palmitoyltransferase activity and chemotaxis.
AB  - Elevated sphingolipids have been associated with increased cardiovascular
      disease. Conversely, atherosclerosis is reduced in mice by blocking de novo
      synthesis of sphingolipids catalyzed by serine palmitoyltransferase (SPT). The
      SPT enzyme is composed of the SPTLC1 and -2 subunits, and here we describe a
      novel protein-protein interaction between SPTLC1 and the PDZ protein Par3
      (partitioning defective protein 3). Mammalian SPTLC1 orthologs have a highly
      conserved C terminus that conforms to a type II PDZ protein interaction motif,
      and by screening PDZ domain protein arrays with an SPTLC1 C-terminal peptide, we
      found it bound the third PDZ domain of Par3. Overlay and immunoprecipitation
      assays confirmed this interaction and indicate Par3 is able to associate with the
      SPTLC1/2 holoenzyme by binding the C-terminal SPTLC1 PDZ motif. The physiologic
      existence of the SPTLC1/2-Par3 complex was detected in mouse liver and
      macrophages, and short interfering RNA inhibition of Par3 in human THP-1
      monocytes significantly reduced SPT activity and de novo ceramide synthesis by
      nearly 40%. Given monocyte recruitment into inflamed vessels is thought to
      promote atherosclerosis, and because Par3 and sphingolipids have been associated
      with polarized cell migration, we tested whether the ability of THP-1 monocytes
      to migrate toward MCP-1 (monocyte chemoattractant protein 1) depended upon Par3
      and SPTLC1 expression. Knockdown of Par3 significantly reduced MCP1-induced
      chemotaxis of THP-1 monocytes, as did knockdown of SPTLC1, and this Par3 effect
      depended upon SPT activity and was blunted by ceramide treatment. In conclusion,
      protein arrays were used to identify a novel SPTLC1-Par3 interaction that
      associates with increased monocyte serine palmitoyltransferase activity and
      chemotaxis toward inflammatory signals.

PMID- 19592498
TI  - Pro-interleukin (IL)-1beta shares a core region of stability as compared with
      mature IL-1beta while maintaining a distinctly different configurational
      landscape: a comparative hydrogen/deuterium exchange mass spectrometry study.
AB  - Interleukin-1beta (IL-1beta) is a master cytokine involved in initiating the
      innate immune response in vertebrates (Dinarello, C. A. (1994) FASEB J. 8, 1314
      1325). It is first synthesized as an inactive 269-residue precursor (pro
      interleukin-1beta or pro-IL-1beta). Pro-IL-1beta requires processing by caspase-1
      to generate the active, mature 153-residue cytokine. In this study, we combined
      hydrogen/deuterium exchange mass spectrometry, circular dichroism spectroscopy,
      and enzymatic digestion comparative studies to investigate the configurational
      landscape of pro-IL-1beta and the role the N terminus plays in modulating the
      landscape. We find that the N terminus keeps pro-IL-1beta in a protease-labile
      state while maintaining a core region of stability in the C-terminal region, the
      eventual mature protein. In mature IL-1beta, this highly protected region maps
      back to the area protected earliest in the NMR studies characterizing an on-route
      kinetic refolding intermediate. This protected region also encompasses two
      important functional loops that participate in the IL-1beta/receptor binding
      interface required for biological activity. We propose that the purpose of the N
      terminal precursor region in pro-IL-1beta is to suppress the function of the
      eventual mature region while keeping a structurally and also functionally
      important core region primed for the final folding into the native, active state
      of the mature protein. The presence of the self-inhibiting precursor region
      provides yet another layer of regulation in the life cycle of this important
      cytokine.

PMID- 19592502
TI  - Licochalcone A potently inhibits tumor necrosis factor alpha-induced nuclear
      factor-kappaB activation through the direct inhibition of IkappaB kinase complex
      activation.
AB  - Glycyrrhiza inflata has been used as a traditional medicine with anti
      inflammatory activity; however, its mechanism has not been fully understood.
      Licochalcone A is a major and biogenetically characteristic chalcone isolated
      from G. inflata. Here, we found that licochalcone A strongly inhibited tumor
      necrosis (TNF)-alpha-induced nuclear localization, DNA binding activity, and the
      transcriptional activity of nuclear factor-kappaB (NF-kappaB). Whereas
      licochalcone A had no effect on the recruitment of receptor-interacting protein 1
      and IkappaB kinase beta (IKKbeta) to TNF receptor I by TNF-alpha, it
      significantly inhibited TNF-alpha-induced IkappaB kinase complex (IKK) activation
      and inhibitor of nuclear factor-kappaB degradation. It is interesting that we
      found that the cysteine residue at position 179 of IKKbeta is essential for
      licochalcone A-induced IKK inhibition, because licochalcone A failed to affect
      the kinase activity of the IKKbeta (C179A) mutant. In contrast, a structurally
      related compound, echinatin, failed to inhibit TNF-alpha-induced IKK activation
      and NF-kappaB activation, suggesting that the 1,1-dimethy-2-propenyl group in
      licochalcone A is important for the inhibition of NF-kappaB. In addition, TNF
      alpha-induced expression of inflammatory cytokines CCL2/monocyte chemotactic
      protein-1and CXCL1/KC was clearly inhibited by licochalcone A but not echinatin.
      Taken together, licochalcone A might contribute to the potent anti-inflammatory
      effect of G. inflata through the inhibition of IKK activation.

PMID- 19592500
TI  - Succination of thiol groups in adipose tissue proteins in diabetes: succination
      inhibits polymerization and secretion of adiponectin.
AB  - S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle
      intermediate fumarate with cysteine residues in protein, a process termed
      succination of protein. Both fumarate and succination of proteins are increased
      in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik,
      M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and
      Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that
      succination of protein is also increased in epididymal, mesenteric, and
      subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a
      major target for succination in both adipocytes and adipose tissue. Cys-39, which
      is involved in cross-linking of adiponectin monomers to form trimers, was
      identified as a key site of succination of adiponectin in adipocytes. 2SC was
      detected on two of seven monomeric forms of adiponectin immunoprecipitated from
      adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin
      accounted for approximately 7 and 8% of total intracellular adiponectin in cells
      and tissue, respectively. 2SC was found only in the intracellular, monomeric
      forms of adiponectin and was not detectable in polymeric forms of adiponectin in
      cell culture medium or plasma. We conclude that succination of adiponectin blocks
      its incorporation into trimeric and higher molecular weight, secreted forms of
      adiponectin. We propose that succination of proteins is a biomarker of
      mitochondrial stress and accumulation of Krebs cycle intermediates in adipose
      tissue in diabetes and that succination of adiponectin may contribute to the
      decrease in plasma adiponectin in diabetes.

PMID- 19592503
TI  - Analysis of 75 marketed pharmaceuticals using the GADD45a-GFP 'GreenScreen HC'
      genotoxicity assay.
AB  - The GADD45a-GFP (GreenScreen HC) reporter assay detects genotoxic damage in the
      human lymphoblastoid TK6 cell line and gives positive results for all classes of
      genotoxin, including mutagens, aneugens and clastogens. In this study, a
      collection of 75 marketed pharmaceuticals were tested in the assay. Compounds in
      the collection represent a broad range of chemical structures, pharmacologies and
      therapeutic indications, including neoplasia and viral infection where positive
      genotoxicity results are often associated with the pharmacological activity.
      Based on the results of this study, two main conclusions can be drawn: (i) the
      GreenScreen HC is more predictive of in vivo genotoxicity (88%) and genotoxic
      carcinogenicity (93%) data than the any of the other regulatory in vitro
      genotoxicity assay and (ii) no compounds were uniquely positive in the GADD45a
      GFP assay. This analysis therefore provides additional evidence to support the
      use of the GADD45a-GFP assay as an effective tool either in early genotoxic
      liability identification or non-clinical safety assessment of candidate
      pharmaceuticals during development.

PMID- 19592501
TI  - Positive feedback regulation of maize NADPH oxidase by mitogen-activated protein
      kinase cascade in abscisic acid signalling.
AB  - In maize (Zea mays), abscisic acid (ABA)-induced H(2)O(2) production activates a
      46 kDa mitogen-activated protein kinase (p46MAPK), and the activation of p46MAPK
      also regulates the production of H(2)O(2). However, the mechanism for the
      regulation of H(2)O(2) production by MAPK in ABA signalling remains to be
      elucidated. In this study, four reactive oxygen species (ROS)-producing NADPH
      oxidase (rboh) genes (ZmrbohA-D) were isolated and characterized in maize leaves.
      ABA treatment induced a biphasic response (phase I and phase II) in the
      expression of ZmrbohA-D and the activity of NADPH oxidase. Phase II induced by
      ABA was blocked by pretreatments with two MAPK kinase (MPKKK) inhibitors and two
      H(2)O(2) scavengers, but phase I was not affected by these inhibitors or
      scavengers. Treatment with H(2)O(2) alone also only induced phase II, and the
      induction was arrested by the MAPKK inhibitors. Furthermore, the ABA-activated
      p46MAPK was partially purified. Using primers corresponding to the sequences of
      internal tryptic peptides, the p46MAPK gene was cloned. Analysis of the tryptic
      peptides and the p46MAPK sequence indicate it is the known ZmMPK5. Treatments
      with ABA and H(2)O(2) led to a significant increase in the activity of ZmMPK5,
      although ABA treatment only induced a slight increase in the expression of
      ZmMPK5. The data indicate that H(2)O(2)-activated ZmMPK5 is involved in the
      activation of phase II in ABA signalling, but not in phase I. The results suggest
      that there is a positive feedback loop involving NADPH oxidase, H(2)O(2), and
      ZmMPK5 in ABA signalling.

PMID- 19592504
TI  - FOXL2 gene mutations and blepharophimosis-ptosis-epicanthus inversus syndrome
      (BPES): a novel mutation detected in a Chinese family and a statistic model for
      summarizing previous reported records.
AB  - Previous studies found that the forkhead transcription factor 2 (FOXL2) gene
      mutations are responsible for both types of blepharophimosis-ptosis-epicanthus
      inversus syndrome (BPES) but have not established any systematic statistic model
      for the complex and even contradictory results about genotype-phenotype
      correlations between them. This study is aimed to find possible mutations of
      FOXL2 gene in a Chinese family with type II BPES by using DNA sequencing and to
      further clarify genotype-phenotype correlations between FOXL2 mutations and BPES
      by using a systematic statistical method, namely Multifactor Dimensionality
      Reduction (MDR). A novel mutation (g.933_965dup) which could result in an
      expansion of the polyalanine (polyAla) tract was detected in all patients of this
      family. MDR analysis for intragenic mutations of FOXL2 gene reported in previous
      BPES studies indicated that the mutations which led to much stronger disturbance
      of amino acid sequence were responsible for more type I BPES, while other kinds
      of mutation were responsible for more type II BPES. In conclusion, the present
      study found a novel FOXL2 gene mutation in a Chinese BPES family and a new
      general genotype-phenotype correlation tendency between FOXL2 intragenic
      mutations and BPES, both of which expanded the knowledge about FOXL2 gene and
      BPES.

PMID- 19592506
TI  - Species-driven changes in nitrogen cycling can provide a mechanism for plant
      invasions.
AB  - Traits that permit successful invasions have often seemed idiosyncratic, and the
      key biological traits identified vary widely among species. This fundamentally
      limits our ability to determine the invasion potential of a species. However,
      ultimately, successful invaders must have positive growth rates that longer term
      result in higher biomass accumulation than competing established species. In many
      terrestrial ecosystems nitrogen limits plant growth, and is a key factor
      determining productivity and the outcome of competition among species. Plant
      nitrogen use may provide a powerful framework to evaluate the invasive potential
      of a species in nitrogen-limiting ecosystems. Six mechanisms influence plant
      nitrogen use or acquisition: photosynthetic tissue allocation, photosynthetic
      nitrogen use efficiency, nitrogen fixation, nitrogen-leaching losses, gross
      nitrogen mineralization, and plant nitrogen residence time. Here we show that
      among these alternatives, the key mechanism allowing invasion for Pinus strobus
      into nitrogen limited grasslands was its higher nitrogen residence time. This
      higher nitrogen residence time created a positive feedback that redistributed
      nitrogen from the soil into the plant. This positive feedback allowed P. strobus
      to accumulate twice as much nitrogen in its tissues and four times as much
      nitrogen to photosynthetic tissues, as compared with other plant species. In
      turn, this larger leaf nitrogen pool increased total plant carbon gain of P.
      strobus two- to sevenfold as compared with other plant species. Thus our data
      illustrate that plant species can change internal ecosystem nitrogen cycling
      feedbacks and this mechanism can allow them to gain a competitive advantage over
      other plant species.

PMID- 19592505
TI  - ETS family transcription factors collaborate with alternative signaling pathways
      to induce carcinoma from adult murine prostate cells.
AB  - Chromosomal rearrangements involving erythroblast transformation specific (ETS)
      family transcription factors were recently defined as the most common genetic
      alterations in human prostate cancer. Despite their prevalence, it is unclear
      what quantitative role they play in either initiation or progression of the
      disease. Using a lentiviral transduction and dissociated cell prostate
      regeneration approach, we find that acutely increased expression of ETS proteins
      in adult murine prostate epithelial cells is sufficient to induce the formation
      of epithelial hyperplasia and focal prostatic intraepithelial neoplasia (PIN)
      lesions, but not progression to carcinoma. However, combined expression of ERG
      with additional genetic alternations associated with human prostate cancer can
      lead to aggressive disease. Although ERG overexpression does not cooperate with
      loss of the tumor suppressor p53, it does collaborate with alterations in PI3K
      signaling, such as Pten knockdown or AKT up-regulation, to produce a well
      differentiated adenocarcinoma. Most striking is our finding that overexpression
      of androgen receptor (AR) does not give rise to any hyperplastic lesions, but
      when combined with high levels of ERG, it promotes the development of a more
      poorly differentiated, invasive adenocarcinoma. These findings suggest that in
      human prostate cancer, the most potent function of ETS gene fusions may be to
      synergize with alternative genetic events and provide different pathways for
      carcinoma production and invasive behavior. Our results provide direct evidence
      for selective cooperating events in ERG-induced prostate tumorigenesis and offer
      a rational basis for combined therapeutic interventions against multiple
      oncogenic pathways in prostate cancer.

PMID- 19592508
TI  - Population stability, cooperation, and the invasibility of the human species.
AB  - The biogeographic expansion of modern humans out of Africa began approximately
      50,000 years ago. This expansion resulted in the colonization of most of the land
      area and habitats throughout the globe and in the replacement of preexisting
      hominid species. However, such rapid population growth and geographic spread is
      somewhat unexpected for a large primate with a slow, density-dependent life
      history. Here, we suggest a mechanism for these outcomes by modifying a simple
      density-dependent population model to allow varying levels of intraspecific
      competition for finite resources. Reducing intraspecific competition increases
      carrying capacities, growth rates, and stability, including persistence times and
      speed of recovery from perturbations. Our model suggests that the energetic
      benefits of cooperation in modern humans may have outweighed the slow rate of
      human population growth, effectively ensuring that once modern humans colonized a
      region long-term population persistence was near inevitable. Our model also
      provides insight into the interplay of structural complexity and stability in
      social species.

PMID- 19592507
TI  - Chimeric transcript discovery by paired-end transcriptome sequencing.
AB  - Recurrent gene fusions are a prevalent class of mutations arising from the
      juxtaposition of 2 distinct regions, which can generate novel functional
      transcripts that could serve as valuable therapeutic targets in cancer.
      Therefore, we aim to establish a sensitive, high-throughput methodology to
      comprehensively catalog functional gene fusions in cancer by evaluating a paired
      end transcriptome sequencing strategy. Not only did a paired-end approach provide
      a greater dynamic range in comparison with single read based approaches, but it
      clearly distinguished the high-level "driving" gene fusions, such as BCR-ABL1 and
      TMPRSS2-ERG, from potential lower level "passenger" gene fusions. Also, the
      comprehensiveness of a paired-end approach enabled the discovery of 12 previously
      undescribed gene fusions in 4 commonly used cell lines that eluded previous
      approaches. Using the paired-end transcriptome sequencing approach, we observed
      read-through mRNA chimeras, tissue-type restricted chimeras, converging
      transcripts, diverging transcripts, and overlapping mRNA transcripts. Last, we
      successfully used paired-end transcriptome sequencing to detect previously
      undescribed ETS gene fusions in prostate tumors. Together, this study establishes
      a highly specific and sensitive approach for accurately and comprehensively
      cataloguing chimeras within a sample using paired-end transcriptome sequencing.

PMID- 19592509
TI  - Glial ephrin-A3 regulates hippocampal dendritic spine morphology and glutamate
      transport.
AB  - Increasing evidence indicates the importance of neuron-glia communication for
      synaptic function, but the mechanisms involved are not fully understood. We
      reported that the EphA4 receptor tyrosine kinase is in dendritic spines of
      pyramidal neurons of the adult hippocampus and regulates spine morphology. We now
      show that the ephrin-A3 ligand, which is located in the perisynaptic processes of
      astrocytes, is essential for maintaining EphA4 activation and normal spine
      morphology in vivo. Ephrin-A3-knockout mice have spine irregularities similar to
      those observed in EphA4-knockout mice. Remarkably, loss of ephrin-A3 or EphA4
      increases the expression of glial glutamate transporters. Consistent with this,
      glutamate transport is elevated in ephrin-A3-null hippocampal slices whereas Eph
      dependent stimulation of ephrin-A3 signaling inhibits glutamate transport.
      Furthermore, some forms of hippocampus-dependent learning are impaired in the
      ephrin-A3-knockout mice. Our results suggest that the interaction between
      neuronal EphA4 and glial ephrin-A3 bidirectionally controls synapse morphology
      and glial glutamate transport, ultimately regulating hippocampal function.

PMID- 19592510
TI  - R2R3-type MYB transcription factor, CmMYB1, is a central nitrogen assimilation
      regulator in Cyanidioschyzon merolae.
AB  - Plant cells sense environmental nitrogen levels and alter their gene expression
      accordingly to survive; however, the underlying regulatory mechanisms still
      remains to be elucidated. Here, we identified and characterized a transcription
      factor that is responsible for expression of nitrogen assimilation genes in a
      unicellular red alga Cyanidioschyzon merolae. DNA microarray and Northern blot
      analyses revealed that transcript of the gene encoding CmMYB1, an R2R3-type MYB
      transcription factor, increased 1 h after nitrogen depletion. The CmMYB1 protein
      started to accumulate after 2 h and reached a peak after 4 h after nitrogen
      depletion, correlating with the expression of key nitrogen assimilation genes,
      such as CmNRT, CmNAR, CmNIR, CmAMT, and CmGS. Although the transcripts of these
      nitrogen assimilation genes were detected in nitrate-grown cells, they
      disappeared upon the addition of preferred nitrogen source such as ammonium or
      glutamine, suggesting the presence of a nitrogen catabolite repression (NCR)
      mechanism. The nitrogen depletion-induced gene expression disappeared in a CmMYB1
      null mutant, and the mutant showed decreased cell viability after exposure to the
      nitrogen-depleted conditions compared with the parental strain. Chromatin
      immunoprecipitation analysis demonstrated that CmMYB1 specifically occupied these
      nitrogen-responsive promoter regions only under nitrogen-depleted conditions, and
      electrophoretic mobility shift assays using crude cell extract revealed specific
      binding of CmMYB1, or a complex containing CmMYB1, to these promoters. Thus, the
      presented results indicated that CmMYB1 is a central nitrogen regulator in C.
      merolae.

PMID- 19592511
TI  - Small-molecule agonists for the thyrotropin receptor stimulate thyroid function
      in human thyrocytes and mice.
AB  - Seven-transmembrane-spanning receptors (7TMRs) are prominent drug targets.
      However, small-molecule ligands for 7-transmembrane-spanning receptors for which
      the natural ligands are large, heterodimeric glycoprotein hormones, like thyroid
      stimulating hormone (TSH; thyrotropin), have only recently been reported, and
      none are approved for human use. We have used quantitative high-throughput
      screening to identify a small-molecule TSH receptor (TSHR) agonist that was
      modified to produce a second agonist with increased potency. We show that these
      agonists are highly selective for human TSHR versus other glycoprotein hormone
      receptors and interact with the receptor's serpentine domain. A binding pocket
      within the transmembrane domain was defined by docking into a TSHR homology model
      and was supported by site-directed mutagenesis. In primary cultures of human
      thyrocytes, both TSH and the agonists increase mRNA levels for thyroglobulin,
      thyroperoxidase, sodium iodide symporter, and deiodinase type 2, and deiodinase
      type 2 enzyme activity. Moreover, oral administration of the agonist stimulated
      thyroid function in mice, resulting in increased serum thyroxine and thyroidal
      radioiodide uptake. Thus, we discovered a small molecule that activates human
      TSHR in vitro, is orally active in mice, and could be a lead for development of
      drugs to use in place of recombinant human TSH in patients with thyroid cancer.

PMID- 19592512
TI  - Replica exchange with nonequilibrium switches.
AB  - We introduce a replica exchange (parallel tempering) method in which attempted
      configuration swaps are generated using nonequilibrium work simulations. By
      effectively increasing phase space overlap, this approach mitigates the need for
      many replicas. We illustrate our method by using a model system and show that it
      is able to achieve the computational efficiency of ordinary replica exchange,
      using fewer replicas.

PMID- 19592513
TI  - War-related exposure and psychological distress as predictors of health and
      sleep: a longitudinal study of Kuwaiti children.
AB  - OBJECTIVES: To determine whether exposure to war-related trauma during childhood
      predicted posttraumatic stress, self-reported health, sleep, and obesity in
      adulthood, and whether psychological distress mediated the relationships.
      METHODS: We assessed 151 Kuwaiti boys and girls aged 9 to 12 years in 1993 to
      determine their level of exposure to war-related trauma during the Iraqi
      occupation and Gulf war, health complaints, and psychological distress. In 2003,
      120 (79%) of the initial participants reported on their posttraumatic stress,
      general health, body mass index (BMI), and sleep quality. We tested a structural
      model where exposure to war-related trauma predicted psychological distress and
      health complaints 2 years after the war, and posttraumatic stress, self-reported
      health, BMI, and sleep quality and duration 10 years later, controlling for
      intermediary life events. We also tested effects of exposure to war-related
      trauma on self-reported health and sleep factors mediated by psychological
      distress. RESULTS: Results indicated a direct effect of exposure on poor sleep
      quality and BMI. Exposure also predicted poor sleep quality through its
      association with concurrent posttraumatic stress. The effect of exposure on self
      reported health was mediated by health complaints and psychological distress,
      which included symptoms of depression, anxiety, and posttraumatic stress.
      CONCLUSION: Exposure to war-related events during childhood is associated with
      posttraumatic stress, poor sleep quality, high BMI, and poor self-reported health
      in adulthood.

PMID- 19592514
TI  - Living alone is associated with an increased risk of type 2 diabetes mellitus in
      men but not women from the general population: the MONICA/KORA Augsburg Cohort
      Study.
AB  - OBJECTIVE: To examine sex-specific associations between living alone and incident
      Type 2 diabetes mellitus in a representative population sample in Germany.
      METHODS: The study was based on 4424 men and 4380 women (aged 35-74 years) who
      participated in one of the three Monitoring trends and determinants on
      cardiovascular diseases Augsburg surveys between 1984 and 1995 and who were free
      of diabetes at baseline. Sex-specific hazard ratios (HRs) were estimated from Cox
      proportional hazard models. RESULTS: A total of 402 cases of incident Type 2
      diabetes among men and 271 among women were registered during the mean follow-up
      period of 10.9 years. Living alone was significantly associated with incident
      Type 2 diabetes in men but not in women. After adjustment for age, survey,
      parental history of diabetes, hypertension, dyslipidemia, smoking, physical
      activity, alcohol intake, and body mass index, the risk of developing diabetes
      for those who lived alone at baseline compared with those who did not live alone
      was 1.69 (95% confidence interval (CI), 1.19-2.37) in men and 0.85 (95% CI, 0.57
      1.24) in women; the p value for the sex interaction was .006 in this model.
      Inclusion of education and depressed mood in the models in addition to other risk
      factors had no impact on the observed HRs in women and even increased the risk in
      men (women: HR, 0.83; 95% CI, 0.52-1.32; men: HR, 1.89; 95% CI, 1.33-2.70).
      CONCLUSIONS: Living alone is an independent predictor of Type 2 diabetes in men
      but not in women from the general population.

PMID- 19592515
TI  - Association of enjoyable leisure activities with psychological and physical well
      being.
AB  - OBJECTIVE: To examine whether engaging in multiple enjoyable activities was
      associated with better psychological and physiological functioning. Few studies
      have examined the health benefits of the enjoyable activities that individuals
      participate in voluntarily in their free time. METHOD: Participants from four
      different studies (n = 1399 total, 74% female, age = 19-89 years) completed a
      self-report measure (Pittsburgh Enjoyable Activities Test (PEAT)) assessing their
      participation in ten different types of leisure activities as well as measures
      assessing positive and negative psychosocial states. Resting blood pressure,
      cortisol (over 2 days), body mass index, waist circumference, and perceived
      physiological functioning were assessed. RESULTS: Higher PEAT scores were
      associated with lower blood pressure, total cortisol, waist circumference, and
      body mass index, and perceptions of better physical function. These associations
      withstood controlling for demographic measures. The PEAT was correlated with
      higher levels of positive psychosocial states and lower levels of depression and
      negative affect. CONCLUSION: Enjoyable leisure activities, taken in the
      aggregate, are associated with psychosocial and physical measures relevant for
      health and well-being. Future studies should determine the extent that these
      behaviors in the aggregate are useful predictors of disease and other health
      outcomes.

PMID- 19592516
TI  - Increased risk of acute myocardial infarction for patients with panic disorder: a
      nationwide population-based study.
AB  - OBJECTIVE: To examine prospectively the relationship between a diagnosis of panic
      disorder and the risk of acute myocardial infarction within 1 year of follow-up.
      Panic disorder is associated prospectively with coronary artery disease, but the
      risk of acute myocardial infarction associated with panic disorder has not been
      specifically investigated. METHOD: This nationwide population-based study used
      data from the Taiwan National Health Insurance Research Database covering the
      years 2000 to 2005. A total of 9641 patients diagnosed with panic disorder in
      2004 were included, together with 28,923 matched nonpanic disorder enrollees as a
      comparison cohort. Cox proportional hazard regressions were conducted to compute
      hazard ratios, after adjustment for comorbid medical disorders and
      sociodemographic characteristics. RESULTS: Results indicated that 4.77% of
      patients with panic disorder (approximately one in 21) experienced an acute
      myocardial infarction episode within a year, compared with 2.73% of patients in
      the comparison cohort. The adjusted hazard of acute myocardial infarction was
      significantly higher (1.75 times, 95% Confidence Interval = 1.55-1.97) for
      patients with panic disorder, relative to the comparison cohort. The association
      persisted in further analyses stratified by hypertension, coronary heart
      diseases, and age. CONCLUSION: Panic disorder was identified as an independent
      risk factor for subsequent acute myocardial infarction. Comprehensive
      multidisciplinary approaches are needed to optimize primary and secondary
      prevention of acute myocardial infarction among patients with panic disorder.

PMID- 19592517
TI  - Is depression after an acute coronary syndrome simply a marker of known
      prognostic factors for mortality?
AB  - OBJECTIVE: Controversy remains over whether the association between depression
      and mortality in patients with acute coronary syndrome (ACS) is confounded by
      incomplete adjustment for measures of known prognostic markers. We assessed a)
      whether depression was associated with the most comprehensive empirically derived
      index of clinical mortality predictors: the Global Registry of Acute Coronary
      Events (GRACE) risk score for predicting 6-month mortality after discharge for
      ACS; and b) whether depression remained an independent predictor of all-cause
      mortality after adjustment for the GRACE score and left ventricular dysfunction.
      METHODS: We surveyed prospectively 457 patients with ACS (aged 25-92 years; 41%
      women, 13% black, and 11% Hispanic), hospitalized between May 2003 and June 2005.
      Depressive symptoms were assessed with the Beck Depression Inventory (BDI) and
      diagnosis of major depressive disorder (MDD) was made by a structured psychiatric
      interview, within 1 week of hospitalization. RESULTS: Despite differences in
      individual components of the GRACE score between depressed and nondepressed
      participants, neither depression measure was associated with overall GRACE score.
      For participants with MDD, the mean +/- standard deviation GRACE score was 84 +/-
      33, compared with 92 +/- 31 for those without MDD (p = .09). Using Cox
      proportional hazards regression analysis, MDD and depressive symptom severity
      each predicted mortality after controlling for GRACE score and left ventricular
      dysfunction (adjusted hazard ratio for MDD = 2.51; 95% Confidence Interval = 1.45
      4.37). CONCLUSION: Depression is not simply a marker of clinical indicators that
      predict all-cause mortality after ACS. This strengthens the assertion that there
      is something unique in the association between depression and post-ACS prognosis,
      independent of known prognostic markers.

PMID- 19592518
TI  - Association of salivary cortisol circadian pattern with cynical hostility: multi
      ethnic study of atherosclerosis.
AB  - OBJECTIVE: To determine if cynical hostility is associated with alterations in
      diurnal profiles of cortisol. Hostility has been linked to cardiovascular disease
      but the biological mechanisms mediating this association remain unknown. METHODS:
      Up to 18 measures of salivary cortisol taken over 3 days were obtained from each
      of 936 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Cynical
      hostility was measured using an eight-item subscale of the Cook-Medley Hostility
      Scale. Cortisol profiles were modeled using regression spline models that
      incorporated random parameters for subject-specific effects. Models were adjusted
      for race, sex, age, socioeconomic position, and lifestyle factors. The
      association of cynical hostility with key features of the cortisol diurnal
      profile, both in the full sample and important subsamples, was examined. RESULTS:
      Waking cortisol levels as well as the extent of the morning surge in cortisol
      levels did not differ significantly across tertiles of cynical hostility.
      Respondents in the lowest tertile of cynical hostility experienced a 22% sharper
      decline in salivary cortisol (age- and sex-adjusted slope of -0.49 microg/dL per
      hour) than respondents in the highest tertile (-0.40 microg/dL per hour, p for
      difference = .0004). Intertertile differences in these parameters remained
      unaltered after further adjustment for potential confounders. This pattern of
      differences in cortisol diurnal profile tended to be related in a dose-response
      way to level of cynical hostility, and persisted in stratified analyses.
      CONCLUSIONS: Cynical hostility is associated with the declining phase of the
      awakening cortisol response. The implications of this for cardiovascular and
      other health outcomes remain to be determined.

PMID- 19592519
TI  - Hostility and platelet reactivity in individuals without a history of
      cardiovascular disease events.
AB  - OBJECTIVE: To examine the association between hostility and platelet reactivity
      in individuals without a prior history of cardiovascular disease (CVD) events.
      Hostility is associated with incident CVD events, independent of traditional risk
      factors. Increased platelet reactivity and thrombus formation over a disrupted
      coronary plaque are fundamental for CVD event onset. METHODS: Hypertensive
      patients (n = 42) without concomitant CVD event history completed the 50-item
      Cook-Medley Hostility Scale, and a subset score of 27 items (Barefoot Ho) was
      derived. We examined the relationship between Barefoot Ho scores and platelet
      aggregation. We also examined individual components of Barefoot Ho (aggressive
      responding, cynicism, and hostile affect) and their associations with platelet
      aggregation. Platelet reactivity, induced by adenosine diphosphate (ADP), was
      assessed by standard light transmission aggregometry, the current gold standard
      method of platelet aggregation assessment. RESULTS: Barefoot Ho scores were
      related significantly to increased rate of platelet aggregation in response to
      ADP. Of the three Barefoot Ho components, only aggressive responding was
      associated independently with increased platelet aggregation rate. The strength
      of these relationships did not diminish after adjusting for several standard CVD
      risk factors. CONCLUSIONS: These data demonstrate that hostility, particularly
      the aggressive responding subtype, is associated with platelet reactivity-a key
      pathophysiological pathway in the onset of CVD events.

PMID- 19592522
TI  - Variability in the prevalence of radiographic stigmata and in their use for
      profiling disease severity makes comparisons more complicated.

PMID- 19592520
TI  - Hostility is associated with visceral, but not subcutaneous, fat in middle-aged
      African American and white women.
AB  - OBJECTIVE: To examine the cross-sectional association between hostility and
      measures of abdominal fat (visceral, subcutaneous) in middle-aged African
      American and white women. Because fat-patterning characteristics are known to
      differ by race, we were particularly interested in examining whether these
      associations were similar for women of both racial/ethnic groups. METHODS:
      Participants were 418 (45% African American, 55% white) middle-aged women from
      the Chicago site of the Study of Women's Health Across the Nation. Visceral and
      subcutaneous fat were measured by computed tomographic scans and hostility was
      assessed via questionnaire. Multivariate linear regression models were conducted
      to test associations among race/ethnicity, hostility, and measures of abdominal
      fat. RESULTS: In models adjusted for race/ethnicity and total percent fat, higher
      levels of hostility were associated with a greater amount of visceral fat (B =
      1.8, standard error = 0.69, p = .01). This association remained significant after
      further adjustments for education, and multiple coronary heart disease (CHD) risk
      factors. Hostility was not associated with subcutaneous fat (p = .8). Although
      there were significant racial/ethnic differences in hostility (p < .001) and the
      amount of total body (p < .001), subcutaneous (p < .001) and visceral fat (p <
      .001), the associations between hostility and measures of abdominal fat did not
      differ for African American compared with white women (race/ethnicity x hostility
      interaction, p = .67 for visceral, p = .85 for subcutaneous). CONCLUSIONS:
      Hostility may affect CHD risk in women via the accumulation of visceral fat.
      Despite significant black-white differences in fat patterning and overall CHD
      risk, the association between hostility and visceral fat seems to be similar for
      both African American and white women.

PMID- 19592523
TI  - Coin rotation task (CRT): a new test of motor dexterity.
AB  - Coin-rotation task (CRT), a measure of rapid, coordinated finger movements, was
      devised as a convenient, easily administered bedside test of motor dexterity;
      however, very little psychometric data exist regarding this task. The current
      project was undertaken to (a) provide preliminary normative data, (b) examine the
      convergent and discriminant validity of the task when compared with other
      standardized motor measures, and (c) examine the diagnostic accuracy of the CRT.
      The sample of 86 male participants included 60 controls and 26 patients with
      unilateral lesions of the left (n = 13) and right (n = 13) hemispheres. The CRT
      was not significantly correlated with age or education; non-adjusted left- and
      right-hand normative data are provided. The CRT demonstrated good convergent and
      divergent validity when compared with other standardized motor measures. The CRT
      was successful in differentiating control and brain damaged groups with mild
      motor impairment, and demonstrated an overall classification rate of 84.9%.
      Levels of sensitivity and specificity of the CRT were comparable with or better
      than other standardized tests of manual dexterity. The CRT offers a valid, quick,
      and convenient bedside measure of subtle motor impairment.

PMID- 19592521
TI  - Joint modeling of longitudinal changes in depressive symptoms and mortality in a
      sample of community-dwelling elderly people.
AB  - OBJECTIVE: To use a joint modeling approach to examine the association between
      longitudinal changes in depressive symptoms and mortality. Research on the
      relationship of depression to mortality has yielded mixed results. Limitations of
      previous studies include mostly one-time assessment of depression, short follow
      ups, and failure to model appropriately changes in depression. METHODS: Data were
      obtained from the Florida Retirement Study, a prospective cohort study of
      community-dwelling oldest old individuals. At baseline, 879 people (mean age =
      80.6 years, 65.8% women) had a comprehensive psychosocial assessment, including
      the Center of Epidemiological Studies-Depression Scale (CES-D). They were then
      assessed annually up to 11 years. Longitudinal changes of CES-D, modeled by a
      joint modeling approach of repeated measures and survival data, were used to
      predict mortality at follow-up (15 years after baseline), at the same time
      adjusting for five classes of covariates. RESULTS: The total mortality rate was
      69.9%. CES-D at baseline was not predictive of mortality at 15-year follow-up
      after adjusting for baseline covariates. The joint modeling revealed that an
      annual increase of 1 point in CES-D scores over the years was associated with a
      57% higher risk of mortality (HR = 1.57, p < .001) at follow-up. Compared with
      those whose CES-D scores were stable over time, subjects with increasing CED-D
      scores over time had a 70% increase in mortality risk, p < .001, and their median
      survival time was 4 years shorter. CONCLUSION: Although baseline CES-D was not
      predictive of mortality, the increase in depressive symptoms over time was
      associated with higher mortality. It is important to assess longitudinal changes
      in depression.

PMID- 19592525
TI  - Modified Bacillus thuringiensis toxins and a hybrid B. thuringiensis strain
      counter greenhouse-selected resistance in Trichoplusia ni.
AB  - Resistance of greenhouse-selected strains of the cabbage looper, Trichoplusia ni,
      to Bacillus thuringiensis subsp. kurstaki was countered by a hybrid strain of B.
      thuringiensis and genetically modified toxins Cry1AbMod and Cry1AcMod, which lack
      helix alpha-1. Resistance to Cry1AbMod and Cry1AcMod was >100-fold less than
      resistance to native toxins Cry1Ab and Cry1Ac.

PMID- 19592524
TI  - Absence of Escherichia coli phylogenetic group B2 strains in humans and
      domesticated animals from Jeonnam Province, Republic of Korea.
AB  - Multiplex PCR analyses of DNAs from genotypically unique Escherichia coli strains
      isolated from the feces of 138 humans and 376 domesticated animals from Jeonnam
      Province, South Korea, performed using primers specific for the chuA and yjaA
      genes and an unknown DNA fragment, TSPE4.C2, indicated that none of the strains
      belonged to E. coli phylogenetic group B2. In contrast, phylogenetic group B2
      strains were detected in about 17% (8 of 48) of isolates from feces of 24 wild
      geese and in 3% (3 of 96) of isolates obtained from the Yeongsan River in Jeonnam
      Province, South Korea. The distribution of E. coli strains in phylogenetic groups
      A, B1, and D varied depending on the host examined, and there was no apparent
      seasonal variation in the distribution of strains in phylogenetic groups among
      the Yeongsan River isolates. The distribution of four virulence genes (eaeA,
      hlyA, stx(1), and stx(2)) in isolates was also examined by using multiplex PCR.
      Virulence genes were detected in about 5% (38 of 707) of the total group of
      unique strains examined, with 24, 13, 13, and 9 strains containing hlyA, eaeA,
      stx(2), and stx(1), respectively. The virulence genes were most frequently
      present in phylogenetic group B1 strains isolated from beef cattle. Taken
      together, results of these studies indicate that E. coli strains in phylogenetic
      group B2 were rarely found in humans and domesticated animals in Jeonnam
      Province, South Korea, and that the majority of strains containing virulence
      genes belonged to phylogenetic group B1 and were isolated from beef cattle.
      Results of this study also suggest that the relationship between the presence and
      types of virulence genes and phylogenetic groupings may differ among
      geographically distinct E. coli populations.

PMID- 19592526
TI  - Large sequence polymorphisms unveil the phylogenetic relationship of
      environmental and pathogenic mycobacteria related to Mycobacterium ulcerans.
AB  - Mycolactone is an immunosuppressive cytotoxin responsible for the clinical
      manifestation of Buruli ulcer in humans. It was believed to be confined to its
      etiologic agent, Mycobacterium ulcerans. However, the identification of other
      mycolactone-producing mycobacteria (MPMs) in other species, including
      Mycobacterium marinum, indicated a more complex taxonomic relationship. This
      highlighted the need for research on the biology, evolution, and distribution of
      such emerging and potentially infectious strains. The reliable genetic
      fingerprinting analyses presented here aim at both the unraveling of phylogenetic
      relatedness and of dispersal between environmental and pathogenic mycolactone
      producers and the identification of genetic prerequisites that enable lateral
      gene transfer of such plasmids. This will allow for the identification of
      environmental reservoirs of virulence plasmids that encode enzymes required for
      the synthesis of mycolactone. Based on dynamic chromosomal loci identified
      earlier in M. ulcerans, we characterized large sequence polymorphisms for the
      phylogenetic analysis of MPMs. Here, we identify new insertional-deletional
      events and single-nucleotide polymorphisms that confirm and redefine earlier
      strain differentiation markers. These results support other data showing that all
      MPMs share a common ancestry. In addition, we found unique genetic features
      specific for M. marinum strain M, the genome sequence strain which is used widely
      in research.

PMID- 19592527
TI  - Potential applicability of chymotrypsin-susceptible microcin J25 derivatives to
      food preservation.
AB  - Microcin J25 (MccJ25) is a 21-residue ribosomally synthesized lariat peptide
      antibiotic. MccJ25 is active against such food-borne disease-causing pathogens as
      Salmonella spp., Shigella spp., and Escherichia coli, including E. coli O157:H7
      and non-O157 strains. MccJ25 is highly resistant to digestion by proteolytic
      enzymes present in the stomach and intestinal contents. MccJ25 would therefore
      remain active in the gastrointestinal tract, affecting normal intestinal
      microbiota, and this limits the potential use of MccJ25 as a food preservative.
      In the present paper, we describe a chymotrypsin-susceptible MccJ25 derivative
      with a mutation of Gly(12) to Tyr that retained almost full antibiotic activity
      and efficiently inhibited the growth of pathogenic Salmonella enterica serovar
      Newport and Escherichia coli O157:H7 in skim milk and egg yolk. However, unlike
      the wild-type MccJ25, the MccJ25(G12Y) variant was inactivated by digestive
      enzymes both in vitro and in vivo. To our knowledge, our results represent the
      first example of a rational modification of a microcin aimed at increasing its
      potential use in food preservation.

PMID- 19592528
TI  - Extracellular iron biomineralization by photoautotrophic iron-oxidizing bacteria.
AB  - Iron oxidation at neutral pH by the phototrophic anaerobic iron-oxidizing
      bacterium Rhodobacter sp. strain SW2 leads to the formation of iron-rich
      minerals. These minerals consist mainly of nano-goethite (alpha-FeOOH), which
      precipitates exclusively outside cells, mostly on polymer fibers emerging from
      the cells. Scanning transmission X-ray microscopy analyses performed at the C K
      edge suggest that these fibers are composed of a mixture of lipids and
      polysaccharides or of lipopolysaccharides. The iron and the organic carbon
      contents of these fibers are linearly correlated at the 25-nm scale, which in
      addition to their texture suggests that these fibers act as a template for
      mineral precipitation, followed by limited crystal growth. Moreover, we evidence
      a gradient of the iron oxidation state along the mineralized fibers at the
      submicrometer scale. Fe minerals on these fibers contain a higher proportion of
      Fe(III) at cell contact, and the proportion of Fe(II) increases at a distance
      from the cells. All together, these results demonstrate the primordial role of
      organic polymers in iron biomineralization and provide first evidence for the
      existence of a redox gradient around these nonencrusting, Fe-oxidizing bacteria.

PMID- 19592530
TI  - Inter- and intraspecies plasmid-mediated transfer of florfenicol resistance in
      Enterobacteriaceae isolates from swine.
AB  - Florfenicol resistance was analyzed in 230 enteric pig isolates collected between
      1998 and 2006. PCR, plasmid profiling, Southern blot hybridization, and a mixed
      broth conjugation assay suggested the intra- and interspecies plasmid-mediated
      transfer of florfenicol resistance among the isolates that exhibited MICs for
      florfenicol between 4 to 128 mg/liter.

PMID- 19592531
TI  - New design strategy for development of specific primer sets for PCR-based
      detection of Chlorophyceae and Bacillariophyceae in environmental samples.
AB  - Studying aquatic microalgae is essential for monitoring biodiversity and water
      quality. We designed new sets of 18S rRNA PCR primers for Chlorophyceae and
      Bacillariophyceae by using the ARB software and implementing a virtual PCR
      program. The results of specificity analysis showed that most of the targeted
      algal families were identified and nontargeted organisms, such as fungi or
      ciliates, were excluded. These newly developed PCR primer sets were also able to
      amplify microalgal rRNA genes from environmental samples with accurate
      specificity. These tools could be of great interest for studying freshwater
      microalgal ecology and for developing bioindicators of the health status of
      aquatic environments.

PMID- 19592532
TI  - Regulatory phenotyping reveals important diversity within the species Lactococcus
      lactis.
AB  - The diversity in regulatory phenotypes among a collection of 84 Lactococcus
      lactis strains isolated from dairy and nondairy origin was explored. The specific
      activities of five enzymes were assessed in cell extracts of all strains grown in
      two different media, a nutritionally rich broth and a relatively poor chemically
      defined medium. The five investigated enzymes, branched chain aminotransferase
      (BcaT), aminopeptidase N (PepN), X-prolyl dipeptidyl peptidase (PepX), alpha
      hydroxyisocaproic acid dehydrogenase (HicDH), and esterase, are involved in
      nitrogen and fatty acid metabolism and catalyze key steps in the production of
      important dairy flavor compounds. The investigated cultures comprise 75 L. lactis
      subsp. lactis isolates (including 7 L. lactis subsp. lactis biovar diacetylactis
      isolates) and 9 L. lactis subsp. cremoris isolates. All L. lactis subsp. cremoris
      and 22 L. lactis subsp. lactis (including 6 L. lactis subsp. lactis biovar
      diacetylactis) cultures originated from a dairy environment. All other cultures
      originated from (fermented) plant materials and were isolated at different
      geographic locations. Correlation analysis of specific enzyme activities revealed
      significantly different regulatory phenotypes for dairy and nondairy isolates.
      The enzyme activities in the two investigated media were in general poorly
      correlated and revealed a high degree of regulatory diversity within this
      collection of closely related strains. To the best of our knowledge, these
      results represent the most extensive diversity analysis of regulatory phenotypes
      within a single bacterial species to date. The presented findings underline the
      importance of the availability of screening procedures for, e.g., industrially
      relevant enzyme activities in models closely mimicking application conditions.
      Moreover, they corroborate the notion that regulatory changes are important
      drivers of evolution.

PMID- 19592533
TI  - Quantitative physiology of Saccharomyces cerevisiae at near-zero specific growth
      rates.
AB  - Growth at near-zero specific growth rates is a largely unexplored area of yeast
      physiology. To investigate the physiology of Saccharomyces cerevisiae under these
      conditions, the effluent removal pipe of anaerobic, glucose-limited chemostat
      culture (dilution rate, 0.025 h(-1)) was fitted with a 0.22-microm-pore-size
      polypropylene filter unit. This setup enabled prolonged cultivation with complete
      cell retention. After 22 days of cultivation, specific growth rates had decreased
      below 0.001 h(-1) (doubling time of >700 h). Over this period, viability of the
      retentostat cultures decreased to ca. 80%. The viable biomass concentration in
      the retentostats could be accurately predicted by a maintenance coefficient of
      0.50 mmol of glucose g(-1) of biomass h(-1) calculated from anaerobic, glucose
      limited chemostat cultures grown at dilution rates of 0.025 to 0.20 h(-1). This
      indicated that, in contrast to the situation in several prokaryotes, maintenance
      energy requirements in S. cerevisiae do not substantially change at near-zero
      specific growth rates. After 22 days of retentostat cultivation, glucose
      metabolism was predominantly geared toward alcoholic fermentation to meet
      maintenance energy requirements. The strict correlation between glycerol
      production and biomass formation observed at higher specific growth rates was not
      maintained at the near-zero growth rates reached in the retentostat cultures. In
      addition to glycerol, the organic acids acetate, d-lactate, and succinate were
      produced at low rates during prolonged retentostat cultivation. This study
      identifies robustness and by-product formation as key issues in attempts to
      uncouple growth and product formation in S. cerevisiae.

PMID- 19592534
TI  - Overproduction of geranylgeraniol by metabolically engineered Saccharomyces
      cerevisiae.
AB  - (E, E, E)-Geranylgeraniol (GGOH) is a valuable starting material for perfumes and
      pharmaceutical products. In the yeast Saccharomyces cerevisiae, GGOH is
      synthesized from the end products of the mevalonate pathway through the
      sequential reactions of farnesyl diphosphate synthetase (encoded by the ERG20
      gene), geranylgeranyl diphosphate synthase (the BTS1 gene), and some endogenous
      phosphatases. We demonstrated that overexpression of the diacylglycerol
      diphosphate phosphatase (DPP1) gene could promote GGOH production. We also found
      that overexpression of a BTS1-DPP1 fusion gene was more efficient for producing
      GGOH than coexpression of these genes separately. Overexpression of the
      hydroxymethylglutaryl-coenzyme A reductase (HMG1) gene, which encodes the major
      rate-limiting enzyme of the mevalonate pathway, resulted in overproduction of
      squalene (191.9 mg liter(-1)) rather than GGOH (0.2 mg liter(-1)) in test tube
      cultures. Coexpression of the BTS1-DPP1 fusion gene along with the HMG1 gene
      partially redirected the metabolic flux from squalene to GGOH. Additional
      expression of a BTS1-ERG20 fusion gene resulted in an almost complete shift of
      the flux to GGOH production (228.8 mg liter(-1) GGOH and 6.5 mg liter(-1)
      squalene). Finally, we constructed a diploid prototrophic strain coexpressing the
      HMG1, BTS1-DPP1, and BTS1-ERG20 genes from multicopy integration vectors. This
      strain attained 3.31 g liter(-1) GGOH production in a 10-liter jar fermentor with
      gradual feeding of a mixed glucose and ethanol solution. The use of bifunctional
      fusion genes such as the BTS1-DPP1 and ERG20-BTS1 genes that code sequential
      enzymes in the metabolic pathway was an effective method for metabolic
      engineering.

PMID- 19592535
TI  - Complete WO phage sequences reveal their dynamic evolutionary trajectories and
      putative functional elements required for integration into the Wolbachia genome.
AB  - Wolbachia endosymbionts are ubiquitously found in diverse insects including many
      medical and hygienic pests, causing a variety of reproductive phenotypes, such as
      cytoplasmic incompatibility, and thereby efficiently spreading in host insect
      populations. Recently, Wolbachia-mediated approaches to pest control and
      management have been proposed, but the application of these approaches has been
      hindered by the lack of genetic transformation techniques for symbiotic bacteria.
      Here, we report the genome and structure of active bacteriophages from a
      Wolbachia endosymbiont. From the Wolbachia strain wCauB infecting the moth
      Ephestia kuehniella two closely related WO prophages, WOcauB2 of 43,016 bp with
      47 open reading frames (ORFs) and WOcauB3 of 45,078 bp with 46 ORFs, were
      characterized. In each of the prophage genomes, an integrase gene and an
      attachment site core sequence were identified, which are putatively involved in
      integration and excision of the mobile genetic elements. The 3' region of the
      prophages encoded genes with sequence motifs related to bacterial virulence and
      protein-protein interactions, which might represent effector molecules that
      affect cellular processes and functions of their host bacterium and/or insect.
      Database searches and phylogenetic analyses revealed that the prophage genes have
      experienced dynamic evolutionary trajectories. Genes similar to the prophage
      genes were found across divergent bacterial phyla, highlighting the active and
      mobile nature of the genetic elements. We suggest that the active WO prophage
      genomes and their constituent sequence elements would provide a clue to
      development of a genetic transformation vector for Wolbachia endosymbionts.

PMID- 19592536
TI  - Role of flagella in virulence of the coral pathogen Vibrio coralliilyticus.
AB  - A recently available transposition system was utilized to isolate a nonmotile
      mutant of the coral-bleaching pathogen Vibrio coralliilyticus. The mutation was
      localized to the fhlA gene, and the mutant lacked flagella. The flhA mutant was
      unable to exhibit chemotaxis toward coral mucus or to adhere to corals and
      subsequently cause infection.

PMID- 19592529
TI  - Defining DNA-based operational taxonomic units for microbial-eukaryote ecology.
AB  - DNA sequence information has increasingly been used in ecological research on
      microbial eukaryotes. Sequence-based approaches have included studies of the
      total diversity of selected ecosystems, studies of the autecology of ecologically
      relevant species, and identification and enumeration of species of interest for
      human health. It is still uncommon, however, to delineate protistan species based
      on their genetic signatures. The reluctance to assign species-level designations
      based on DNA sequences is in part a consequence of the limited amount of sequence
      information presently available for many free-living microbial eukaryotes and in
      part a consequence of the problematic nature of and debate surrounding the
      microbial species concept. Despite the difficulties inherent in assigning species
      names to DNA sequences, there is a growing need to attach meaning to the
      burgeoning amount of sequence information entering the literature, and there is a
      growing desire to apply this information in ecological studies. We describe a
      computer-based tool that assigns DNA sequences from environmental databases to
      operational taxonomic units at approximately species-level distinctions. This
      approach provides a practical method for ecological studies of microbial
      eukaryotes (primarily protists) by enabling semiautomated analysis of large
      numbers of samples spanning great taxonomic breadth. Derivation of the algorithm
      was based on an analysis of complete small-subunit (18S) rRNA gene sequences and
      partial gene sequences obtained from the GenBank database for morphologically
      described protistan species. The program was tested using environmental 18S rRNA
      data sets for two oceanic ecosystems. A total of 388 operational taxonomic units
      were observed for 2,207 sequences obtained from samples collected in the western
      North Atlantic and eastern North Pacific oceans.

PMID- 19592537
TI  - Quantitative PCR for genetic markers of human fecal pollution.
AB  - Assessment of health risk and fecal bacterial loads associated with human fecal
      pollution requires reliable host-specific analytical methods and a rapid
      quantification approach. We report the development of quantitative PCR assays for
      quantification of two recently described human-specific genetic markers targeting
      Bacteroidales-like cell surface-associated genes. Each assay exhibited a range of
      quantification from 10 to 1 x 10(6) copies of target DNA. For each assay,
      internal amplification controls were developed to detect the presence or absence
      of amplification inhibitors. The assays predominantly detected human fecal
      specimens and exhibited specificity levels greater than 97% when tested against
      265 fecal DNA extracts from 22 different animal species. The abundance of each
      human-specific genetic marker in primary effluent wastewater samples collected
      from 20 geographically distinct locations was measured and compared to quantities
      estimated by real-time PCR assays specific for rRNA gene sequences from total
      Bacteroidales and enterococcal fecal microorganisms. Assay performances combined
      with the prevalence of DNA targets in sewage samples provide experimental
      evidence supporting the potential application of these quantitative methods for
      monitoring fecal pollution in ambient environmental waters.

PMID- 19592538
TI  - Quantitative PCR for determining the infectivity of bacteriophage MS2 upon
      inactivation by heat, UV-B radiation, and singlet oxygen: advantages and
      limitations of an enzymatic treatment to reduce false-positive results.
AB  - Health risks posed by waterborne viruses are difficult to assess because it is
      tedious or impossible to determine the infectivity of many viruses. Recent
      studies hypothesized that quantitative PCR (qPCR) could selectively quantify
      infective viruses if preceded by an enzymatic treatment (ET) to reduce
      confounding false-positive signals. The goal of this study was to determine if ET
      with qPCR (ET-qPCR) can be used to accurately quantify the infectivity of the
      human viral surrogate bacteriophage MS2 upon partial inactivation by three
      treatments (heating at 72 degrees C, singlet oxygen, and UV radiation). Viruses
      were inactivated in buffered solutions and a lake water sample and assayed with
      culturing, qPCR, and ET-qPCR. To ensure that inactivating genome damage was fully
      captured, primer sets that covered the entire coding region were used. The
      susceptibility of different genome regions and the maximum genomic damage after
      each inactivating treatment were compared. We found that (i) qPCR alone caused
      false-positive results for all treatments, (ii) ET-qPCR significantly reduced (up
      to >5.2 log units) but did not eliminate the false-positive signals, and (iii)
      the elimination of false-positive signals differed between inactivating
      treatments. By assaying the whole coding region, we demonstrated that genome
      damage only partially accounts for virus inactivation. The possibility of
      achieving complete accordance between culture- and PCR-based assays is therefore
      called into doubt. Despite these differences, we postulate that ET-qPCR can track
      infectivity, given that decreases in infectivity were always accompanied by dose
      dependent decreases in ET-qPCR signal. By decreasing false-positive signals, ET
      qPCR improved the detection of infectivity loss relative to qPCR.

PMID- 19592539
TI  - Understanding barriers to delirium care: a multicentre survey of knowledge and
      attitudes amongst UK junior doctors.
AB  - BACKGROUND: delirium is under-diagnosed and under-treated in comparison to other
      common and serious acute disorders. The reasons for this are unclear. OBJECTIVE:
      we conducted a multicentre survey of knowledge of and attitudes to delirium in
      trainee general physicians. DESIGN: questionnaire-based survey in 34 acute
      hospitals in the UK. METHODS: we developed a questionnaire designed to test
      knowledge of delirium prevalence, DSM-IV diagnostic criteria, use of specific
      screening tools, association with adverse outcomes, and pharmacological
      management. Questionnaires were completed and returned by hand to the researchers
      immediately after recruitment. Participants were a convenience sample of trainee
      doctors in general and emergency medicine. RESULTS: 784 trainee physicians
      participated. Most participants expressed the view that delirium has a high
      prevalence and that it is associated with serious adverse outcomes. However, they
      had poor knowledge of its diagnosis and treatment, reporting the need for better
      training. Experience working in geriatric medicine had only a modest effect on
      the ability to diagnose delirium. CONCLUSIONS: UK training doctors' lack of basic
      knowledge of the diagnosis and management of delirium, rather than a lack of
      awareness of its high prevalence and clinical significance, appears to be
      important in determining its under-recognition.

PMID- 19592540
TI  - The future of thoracoscopic lobectomy in lung cancer.

PMID- 19592541
TI  - Off-pump coronary artery bypass for emergency myocardial revascularization.
AB  - Emergency coronary artery bypass is associated with increased operative
      mortality. The objective of this study was to evaluate the efficiency and safety
      of off-pump emergency coronary artery bypass, and to compare the outcome with
      that of the conventional on-pump procedure. Data of 79 patients who underwent
      emergency isolated coronary artery bypass were reviewed retrospectively; 45 had
      off-pump coronary bypass and 34 had conventional surgery. In the off-pump group,
      mean ejection fraction was significantly lower (28% +/- 9% vs. 39% +/- 10%), and
      there were fewer grafts per patient (1.8 +/- 0.7 vs. 3.2 +/- 0.8). Early
      mortality was higher in the conventional surgery group (14.7% vs. 8.9%), but late
      mortality was similar in both groups. Patients who had on-pump surgery had lower
      rates of recurrent angina (16% vs. 34%) and symptoms of heart failure (20% vs.
      51%). Re-hospitalization was more common in off-pump patients, but cardiac re
      interventions were similar. There was no significant difference in 5-year
      survival rates. The results of off-pump coronary bypass were better than the
      preoperative predicted EuroSCORE, thus it was concluded that patients treated on
      an emergency basis should have an off-pump revascularization procedure.

PMID- 19592542
TI  - Clinical determinants of ckit-positive cardiac cell yield in coronary disease.
AB  - Recent animal studies and clinical trials have reported the scope of heart
      resident ckit-positive stem cells in regenerating infarcted myocardium. The
      determinants of successful isolation of such cells are unknown. The objective of
      this study was to determine the influence of risk factors for coronary artery
      disease and disease severity on the successful isolation of ckit-positive cells
      from right atrial tissue of patients with coronary artery disease. The findings
      suggest that coronary artery disease and cardiac remodeling in chronic ischemia
      may not affect the yield of ckit-positive cells from atrial tissue, but a
      significant negative correlation between the age of the patient and the number of
      migrated ckit-positive cells was observed. This suggests that in older patients,
      stem cell isolation from cardiac biopsies may not succeed, and such cells may not
      be available for cell therapy.

PMID- 19592543
TI  - Radial artery jump graft from anterior to posterior descending coronary artery.
AB  - A novel technique to achieve total arterial grafting, using a radial artery jump
      graft from the anterior descending coronary artery to the posterior descending
      artery, was employed in a preliminary series of 10 patients. All radial artery
      grafts were patent. This was confirmed using the SPY intraoperative fluorescence
      imaging system. There were no postoperative complications in any patient, and all
      were discharged uneventfully.

PMID- 19592544
TI  - Short- and long-term results of lung resection for cancer in octogenarians.
AB  - To analyze short- and long-term results of surgery in octogenarians, we reviewed
      data of 96 consecutive patients aged 80 years or more who were operated on for
      non-small-cell lung carcinoma from 1990 to 2005. Risk factors for complications,
      perioperative mortality, and long-term survival were assessed by univariate and
      multivariate analysis. Major complications developed in 17 (17.7%) patients,
      leading to death in 9 (9.4%) of them. Resection of more than 1 lobe,
      cardiorespiratory comorbidity, PaO2 < 75 mm Hg, and CO diffusion capacity <60%
      were predictive of major complications; extended resection was also predictive of
      30-day mortality. The overall 5-year survival rate was 38%, with a significant
      difference between stage I/II and stage III. In multivariate analysis only
      pathological stage was related to long-term survival. Surgery is feasible for
      octogenarians, and even patients in stage II can achieve remarkable survival.

PMID- 19592545
TI  - Preserving middle lobe to improve lung function in non-small-cell lung cancer.
AB  - When a lung tumor arises in segment 6, the close anatomical relationship to the
      middle lobe bronchus may make a lower bilobectomy necessary. Sleeve lobectomy may
      be an alternative. These procedures were compared retrospectively in 36 patients
      operated on between January 2005 and December 2006 with non-small-cell lung
      cancer (stage I-IIIB) of the right lower lobe. Sleeve lobectomy was performed in
      21 patients and bilobectomy in 15 (41%). Preoperative lung function was
      comparable in both groups. Radical resection was achieved in 34/36 patients.
      Operation time was 121 min for sleeve lobectomy and 144 min for bilobectomy.
      Chest tubes were removed after 5 days in both groups. Postoperative lung function
      was better after sleeve lobectomy than bilobectomy (forced expiratory volume in
      1st sec: 78% vs. 69%). Preservation of the middle lobe by sleeve lobectomy is
      feasible. There was no evidence that this resection was less radical, and
      complication rates were similar in both groups.

PMID- 19592546
TI  - Expression of Pin1 mRNA in non-small-cell lung cancer patients.
AB  - Phosphorylation of proteins on serine or threonine residues preceding proline is
      a major regulatory mechanism in cell proliferation and transformation, which is
      catalyzed specifically by Pin1, a peptidylprolyl isomerase. Pin1 is overexpressed
      in several human cancers. The expression of Pin1 mRNA in the circulation was
      assessed in 26 patients with non-small-cell lung cancer who underwent surgical
      resection. They were randomly assigned to a pulmonary artery first ligation group
      and a pulmonary vein first ligation group. Pin1 mRNA expression in blood samples
      from patients with lung cancer, controls with benign lung disease, and healthy
      subjects were determined by a real-time reverse transcriptase polymerase chain
      reaction. Compared to those with benign lung disease and healthy controls, Pin1
      mRNA was overexpressed in patients with non-small-cell lung cancer, and the
      levels correlated with lymph node-positive disease and tumor stage. Expression of
      Pin1 mRNA in the distal part of the pulmonary vein was significantly higher than
      in the proximal part. Postoperative Pin1 mRNA expression was significant lower
      than preoperative expression. There was no significant difference in Pin1
      expression between groups based on pulmonary vessel ligation. These findings
      suggest that Pin1 might be a useful tumor marker for cancer therapy.

PMID- 19592547
TI  - Reduction aortoplasty for ascending aortic aneurysm: a 14-year experience.
AB  - We present early results and long-term follow-up after reduction aortoplasty with
      external wrapping of the ascending aorta. From December 1993 to February 2008, 32
      consecutive patients who had reduction aortoplasty were compared with 47
      consecutive patients who underwent prosthetic graft replacement of the ascending
      aorta. The groups were similar in baseline characteristics. Patients in the
      reduction aortoplasty group had significantly shorter aortic crossclamp times
      (18.78 +/- 1.91 vs. 34.04 +/- 3.25 min) and cardiopulmonary bypass times (30.16
      +/- 2.36 vs. 60.83 +/- 2.05 min), and they received fewer transfusions. There was
      no significant enlargement of the aortic diameter at the level of the sinus of
      Valsalva in the reduction aortoplasty group during the follow-up period (from
      38.84 +/- 3.10 to 39.48 +/- 2.72 mm). Reduction aortoplasty with external
      wrapping of the ascending aorta is a simple and promising surgical method. Our
      experience shows that this technique is the procedure of choice in patients
      without aortic dissection and with an appropriately sized sinus of Valsalva.

PMID- 19592548
TI  - Sternal weave in high-risk patients to prevent noninfective sternal dehiscence.
AB  - Dehiscence of the sternum is a serious and potentially devastating complication.
      The purpose of this prospective study was to determine whether a prophylactic
      sternal weave would decreased the incidence of noninfective sternal dehiscence,
      compared to routine sternal closure, in a high-risk group. Between 2000 and 2007,
      200 patients undergoing median sternotomy for cardiac surgery, with one or more
      risk factors including New York Heart Association functional class III/IV,
      chronic obstructive pulmonary disease, osteoporosis, obesity, and off-midline
      sternotomy, were randomly assigned to group A (sternal weave closure, 100
      patients) or group B (routine sternal wire closure, 100 patients). No patient in
      either group with a single risk factor had sternal dehiscence. The incidence of
      noninfective sternal dehiscence was significantly less in group A than group B in
      patients with 2 or more risk factors (2.5% vs. 12.5%). Routine sternal closure is
      sufficient in patients with a single risk factor, whereas a prophylactic sternal
      weave should be carried out in all patients with 2 or more risk factors, to
      decrease postoperative morbidity.

PMID- 19592549
TI  - Improved combined superior-transseptal approach to the mitral valve.
AB  - In mitral valve surgery, the combined superior-transseptal approach gives
      excellent exposure of the mitral valve, but it is lengthy and complex. A modified
      version of this approach was made without cutting the right atrial appendage and
      the dome of the right atrium. This shorter procedure was evaluated in 30 patients
      aged 4-61 years undergoing complex mitral valve operations including mitral
      repair (33.3%), reoperation (30%), and small left atrium (30%). The mitral valve
      was exposed well in all cases. Because of the shorter incision, closure was
      relatively easy. The aortic crossclamp time was 117 +/- 29.9 min (range, 53-173).
      There were no major complications. Cardiac rhythm resumed spontaneously after
      release of the aortic clamp in 93.3% of patients, including 36.7% who regained
      sinus rhythm from arrhythmia preoperatively. There was no heart block, bleeding,
      or mortality. Results at 3 months were good. Despite a decreased operative field,
      this modified approach provided adequate exposure for all the required
      techniques. The benefits of this approach are a shorter incision in the atrial
      muscle, and simplified closure technique.

PMID- 19592550
TI  - Comparative analysis and outcomes of sleeve resection versus pneumonectomy.
AB  - To compare the outcome of sleeve resection or complex sleeve resection versus
      (Vs) pneumonectomy for lung cancer in a single unit. Between 1998 and 2006, 664
      lung resections were carried out. There were 129 (19.4%) pneumonectomies and 79
      (11.9%) sleeve resections; Twenty one patients (26.5%) underwent a complex sleeve
      resection. Operative mortality for the sleeve resections (SR) was 2.5% and for
      the pneumonectomies 8.53%. Overall 5-year survival after SR was 46.8% and after
      pneumonectomy 37.1%. The survival curves for the 2 procedures after adjusting for
      risk factors are different. The area under the curve is higher for the SR (Hazard
      ratio 1.78 C.I.: 0.92-3.46). The 5-year survival for early stages favors SR. The
      survival for the complex SR was not influenced by the complexity of the procedure
      but from the TNM stage of each individual case. Multivariate analysis of risk
      factors affecting survival after surgery showed: male sex Hazard ratio (HR) 1.19,
      0.63-2.27(95%CI), Age >63 1.38(HR), 0.78-2.48, Pneumonectomy 1.78(HR), 0.92-3.46
      and stage III 4.44(HR), 1.94-10.16(95% CI). For comparative stages survival
      appears to be better after sleeves, moreover male sex, sleeve resection, age
      younger that 63 and early TNM stage are positive predictors for survival.

PMID- 19592551
TI  - Extraanatomic bypass and coronary artery grafting for coral reef aorta.
AB  - A 63-year-old man complained of abdominal angina and intermittent claudication.
      Multidimensional angiography showed focal calcified obstruction of the suprarenal
      aorta, occlusion of the right external iliac artery, and instent restenosis in
      the right coronary artery. Extraanatomic bypass was performed from the ascending
      aorta to the left external iliac and right femoral arteries, using an 8-mm
      bifurcated graft, with concomitant off-pump coronary artery grafting. The
      patient's digestive symptoms and leg claudication disappeared.

PMID- 19592552
TI  - Repair of narrowed coronary sinus without connecting left superior vena cava.
AB  - We successfully repaired a markedly narrowed coronary sinus without connecting a
      left superior vena cava in a 3-year-old boy with an atrial septal defect.

PMID- 19592553
TI  - Pericardial adhesions simulating myocardial bridging.
AB  - A 48-year-old man with aortic valve disease was diagnosed to have myocardial
      bridging on preoperative coronary angiography. During surgical exploration, only
      pericardial adhesions were found, with a normal epicardial coronary course.

PMID- 19592554
TI  - Complete lobar torsion simulating hemorrhagic shock after left upper lobectomy.
AB  - Lung torsion is a rare but serious complication after thoracic operations. We
      describe an unusual case of left lobar torsion after video-assisted thoracoscopic
      upper lobectomy. The profound symptom was impending hemorrhagic shock, which
      masqueraded as postoperative bleeding. The differentials between these 2 entities
      and treatment options for lung torsion are discussed.

PMID- 19592555
TI  - Eosinophilic granuloma of the lung and rib.
AB  - Langerhans-cell histiocytosis is characterized by abnormal proliferation of
      Langerhans cells, and frequently associated with cigarette smoking. A 24-year-old
      man who underwent excisional biopsy of a pulmonary nodule and segmental rib
      resection was found to have the eosinophilic granuloma variation of Langerhans
      cell histiocytosis.

PMID- 19592556
TI  - Management of lobar torsion following lung transplantation.
AB  - We report 4 cases of acute lobar torsion in patients who had undergone bilateral
      lung transplantation. Bronchoscopy showed complete obstruction in only 2 of them.
      Torsion was confirmed by computed tomography in coronal minimal and maximal
      intensity projections with reconstruction. At operation, 1 detorsion and 3
      lobectomies were carried out. Early diagnosis and rapid surgical intervention can
      save the affected lobe.

PMID- 19592557
TI  - A rare case of adult pulmonary myofibromatosis.
AB  - Suspicious bilateral lung nodes were detected incidentally in a 49-year-old man
      who had undergone a homograft kidney transplant 6 years earlier. Two nodules were
      excised by a video-assisted left minithoracotomy. The morphological and
      immunohistochemical patterns were compatible with a diagnosis of pulmonary
      myofibromatosis.

PMID- 19592558
TI  - Long-term survival of Uhl's anomaly with total cavopulmonary conversion.
AB  - We report a long-term survivor with Uhl's anomaly who underwent one and a half
      ventricle repair combined with a partial right ventriculectomy in infancy,
      followed by successful total cavopulmonary conversion with right ventricular
      exclusion 5 years later. The combination of total cavopulmonary connection and
      right ventricular exclusion could be the optimal surgical option for a critically
      ill infant with Uhl's anomaly.

PMID- 19592559
TI  - Self-retaining pledgeted suture as retractor for mitral procedure.
AB  - A simple reliable maneuver to optimize exposure of the left atrium for mitral
      valve operations is described. It offers more space to mobilize the valvular
      structure, facilitating complicated reconstruction in the posteromedial
      commisural area.

PMID- 19592560
TI  - Current trends in extended lymph node dissection for esophageal carcinoma.
AB  - Extended lymph node dissection helps increase the curativeness of resection, the
      accuracy of surgical-pathological staging, and the prognosis of thoracic
      esophageal carcinoma. However, it is also associated with significantly increased
      surgical morbidity and has noticeable negative effects on the quality of life
      after surgery. Current trends for selective lymph node dissection based on
      clinical evidence may be helpful in reducing surgical risks while assuring the
      completeness of resection.

PMID- 19592561
TI  - Right aortic arch and aberrant left subclavian artery.

PMID- 19592562
TI  - Giant ascending aortic aneurysm in 13-year-old patient.

PMID- 19592563
TI  - Expanding cardiac vascular mass: an unusual cause of cardiomegaly.

PMID- 19592564
TI  - Left ventricular aneurysm with a calcified thrombus at the apex.

PMID- 19592567
TI  - Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by
      generating hydrogen peroxide.
AB  - AIMS: Our objective was to investigate whether pro-oxidant properties of ascorbic
      acid (AA) and tetrahydrobiopterin (BH(4)) modulate endothelium-dependent,
      electrotonically mediated arterial relaxation. METHODS AND RESULTS: In studies
      with rabbit iliac artery (RIA) rings, NO-independent, endothelium-derived
      hyperpolarizing factor (EDHF)-type relaxations evoked by the sarcoplasmic
      endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid and the G
      protein-coupled agonist acetylcholine (ACh) were enhanced by AA (1 mM) and BH(4)
      (200 microM), which generated buffer concentrations of H(2)O(2) in the range of
      40-80 microM. Exogenous H(2)O(2) potentiated cyclopiazonic acid (CPA)- and ACh
      evoked relaxations with a threshold of 10-30 microM, and potentiation by AA and
      BH(4) was abolished by catalase, which destroyed H(2)O(2) generated by oxidation
      of these agents in the organ chamber. Adventitial application of H(2)O(2) also
      enhanced EDHF-type dilator responses evoked by CPA and ACh in RIA segments
      perfused intraluminally with H(2)O(2)-free buffer, albeit with reduced efficacy.
      In RIA rings, both control relaxations and their potentiation by H(2)O(2) were
      overcome by blockade of gap junctions by connexin-mimetic peptides (YDKSFPISHVR
      and SRPTEK) targeted to the first and second extracellular loops of the dominant
      vascular connexins expressed in the RIA. Superoxide dismutase attenuated the
      potentiation of EDHF-type relaxations by BH(4), but not AA, consistent with
      findings demonstrating a differential role for superoxide anions in the
      generation of H(2)O(2) by the two agents. CONCLUSION: Pro-oxidant effects of AA
      and BH(4) can enhance the EDHF phenomenon by generating H(2)O(2), which has
      previously been shown to amplify electrotonic hyperpolarization-mediated
      relaxation by facilitating Ca(2+) release from endothelial stores.

PMID- 19592569
TI  - Attenuated store-operated Ca2+ entry underpins the dual inhibition of nitric
      oxide and EDHF-type relaxations by iodinated contrast media.
AB  - AIMS: Our objective was to investigate whether alterations in endothelial Ca(2+)
      homeostasis contribute to the clinical toxicity of iodinated radiographic
      contrast media (IRCM) by modulating nitric oxide (NO) production and the
      endothelium-derived hyperpolarizing factor (EDHF) phenomenon. METHODS AND
      RESULTS: The triiodinated monomer iohexol caused concentration-dependent
      reductions in store-operated Ca(2+) entry (SOCE) in rabbit aortic valve
      endothelium incubated in Ca(2+)-free buffer with cyclopiazonic acid (CPA, 30
      microM) to deplete endoplasmic reticulum Ca(2+) stores. This action was mimicked
      by Gd(3+) ions and 2-aminoethoxydiphenyl borate, two established inhibitors of
      SOCE, whereas Ca(2+) entry was unaffected by the osmotic agent mannitol.
      Immunohistochemistry demonstrated that iohexol did not prevent CPA-evoked
      membrane clustering of Orai1, the key pore element of the store-operated Ca(2+)
      channel (SOC) apparatus. In myograph studies with rabbit iliac artery rings,
      iohexol, and the hexaiodinated dimer iodixanol (both at 90 mg I/mL) attenuated NO
      mediated and EDHF-type arterial relaxations evoked by CPA, but did not affect
      EDHF-type relaxations to acetylcholine, whose principal mode of action is to
      mobilize Ca(2+) via inositol 1,4,5-trisphosphate (InsP(3))-induced Ca(2+)
      release. Iohexol also exerted inhibitory effects on NO-mediated relaxation and
      smooth muscle contraction that were not evident with iodixanol. CONCLUSIONS: The
      data support the hypothesis that IRCM induce generalized endothelial dysfunction
      by inhibiting Ca(2+) influx via SOCs rather than their assembly. The presence of
      organically bound iodine, rather than osmolar effects, may underpin this
      previously unrecognized phenomenon. In contrast, direct effects of IRCM on smooth
      muscle function may correlate with osmolarity rather than iodine concentration.

PMID- 19592568
TI  - The anti-inflammatory agent bindarit inhibits neointima formation in both rats
      and hyperlipidaemic mice.
AB  - AIMS: Bindarit is an original compound with peculiar anti-inflammatory activity
      due to a selective inhibition of a subfamily of inflammatory chemokines,
      including the monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7, and MCP
      2/CCL8. In this study, we investigated the effect of bindarit on neointima
      formation using two animal models of arterial injury: rat carotid artery balloon
      angioplasty and wire-induced carotid injury in apolipoprotein E-deficient (apoE(
      /-)) mice. METHODS AND RESULTS: Treatment of rats with bindarit (200 mg/kg/day)
      significantly reduced balloon injury-induced neointima formation by 39% at day 14
      without affecting re-endothelialization and reduced the number of medial and
      neointimal proliferating cells at day 7 by 54 and 30%, respectively. These
      effects were associated with a significant reduction of MCP-1 levels both in sera
      and in injured carotid arteries of rats treated with bindarit. In addition, in
      vitro data showed that bindarit (10-300 microM) reduced rat vascular smooth
      muscle cell (VSMC) proliferation, migration, and invasion, processes contributing
      to the injury-induced neointima formation in vivo. Similar results were observed
      in hypercholesterolaemic apoE(-/-) mice in which bindarit administration resulted
      in a 42% reduction of the number of proliferating cells at day 7 after carotid
      injury and in a 47% inhibition of neointima formation at day 28. Analysis of the
      cellular composition in neointimal lesions of apoE(-/-) mice treated with
      bindarit showed that the relative content of macrophages and the number of VSMCs
      were reduced by 66 and 30%, respectively, compared with the control group.
      CONCLUSION: This study demonstrates that bindarit is effective in reducing
      neointima formation in both non-hyperlipidaemic and hyperlipidaemic animal models
      of vascular injury by a direct effect on VSMC proliferation and migration and by
      reducing neointimal macrophage content. All of these data were associated with
      the inhibition of MCP-1 production.

PMID- 19592572
TI  - Shape meets polarity in Japan.
AB  - A diverse group of developmental biologists who study cell polarity gathered in
      late March 2009 at the RIKEN Center for Developmental Biology in Kobe, Japan, for
      a symposium entitled ;Shape and Polarity'. The organizers, Masatoshi Takeichi,
      Fumio Matsuzaki, Hitoshi Sawa [RIKEN Center for Developmental Biology (CDB),
      Kobe, Japan] and Carl-Philipp Heisenberg (Max Planck Institute, Dresden,
      Germany), put together an engaging program that highlighted recent progress
      towards understanding the mechanisms of cell polarization during development, and
      the functions of cell polarity in shaping development.

PMID- 19592570
TI  - Absolute pitch--functional evidence of speech-relevant auditory acuity.
AB  - Absolute pitch (AP) has been shown to be associated with morphological changes
      and neurophysiological adaptations in the planum temporale, a cortical area
      involved in higher-order auditory and speech perception processes. The direct
      link between speech processing and AP has hitherto not been addressed. We provide
      first evidence that AP compared with relative pitch (RP) ability is associated
      with significantly different hemodynamic responses to complex speech sounds. By
      systematically varying the lexical and/or prosodic information of speech stimuli,
      we demonstrated consistent activation differences in AP musicians compared with
      RP musicians and nonmusicians. These differences relate to stronger activations
      in the posterior part of the middle temporal gyrus and weaker activations in the
      anterior mid-part of the superior temporal gyrus. Furthermore, this pattern is
      considerably modulated by the auditory acuity of AP. Our results suggest that the
      neural underpinnings of pitch processing expertise exercise a strong influence on
      propositional speech perception (sentence meaning).

PMID- 19592571
TI  - Segregated fronto-cerebellar circuits revealed by intrinsic functional
      connectivity.
AB  - Multiple, segregated fronto-cerebellar circuits have been characterized in
      nonhuman primates using transneuronal tracing techniques including those that
      target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in
      humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits
      that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial
      prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were
      replicated and dissociated in an independent data set (n = 40). Direct comparison
      of right- and left-seeded frontal regions revealed contralateral lateralization
      in the cerebellum for each of the segregated circuits. The presence of circuits
      that involve prefrontal regions confirms that the cerebellum participates in
      networks important to cognition including a specific fronto-cerebellar circuit
      that interacts with the default network. Overall, the extent of the cerebellum
      associated with prefrontal cortex included a large portion of the posterior
      hemispheres consistent with a prominent role of the cerebellum in nonmotor
      functions. We conclude by providing a provisional map of the topography of the
      cerebellum based on functional correlations with the frontal cortex.

PMID- 19592573
TI  - Lighting up mRNA localization in Drosophila oogenesis.
AB  - The asymmetric localization of four maternal mRNAs - gurken, bicoid, oskar and
      nanos - in the Drosophila oocyte is essential for the development of the
      embryonic body axes. Fluorescent imaging methods are now being used to visualize
      these mRNAs in living tissue, allowing dynamic analysis of their behaviors
      throughout the process of localization. This review summarizes recent findings
      from such studies that provide new insight into the elaborate cellular mechanisms
      that are used to transport mRNAs to different regions of the oocyte and to
      maintain their localized distributions during oogenesis.

PMID- 19592575
TI  - Fascin is required for blood cell migration during Drosophila embryogenesis.
AB  - Fascin is well characterized in vitro as an actin-bundling protein and its
      increased expression is correlated with the invasiveness of various cancers.
      However, the actual roles and regulation of Fascin in vivo remain elusive. Here
      we show that Fascin is required for the invasive-like migration of blood cells in
      Drosophila embryos. Fascin expression is highly regulated during embryonic
      development and, within the blood lineage, is specific to the motile
      subpopulation of cells, which comprises macrophage-like plasmatocytes. We show
      that Fascin is required for plasmatocyte migration, both as these cells undergo
      developmental dispersal and during an inflammatory response to epithelial
      wounding. Live analyses further demonstrate that Fascin localizes to, and is
      essential for the assembly of, dynamic actin-rich microspikes within plasmatocyte
      lamellae that polarize towards the direction of migration. We show that a
      regulatory serine of Fascin identified from in vitro studies is not required for
      in vivo cell motility, but is crucial for the formation of actin bundles within
      epithelial bristles. Together, these results offer a first glimpse into the
      mechanisms regulating Fascin function during normal development, which might be
      relevant for understanding the impact of Fascin in cancers.

PMID- 19592574
TI  - Nkx6-1 controls the identity and fate of red nucleus and oculomotor neurons in
      the mouse midbrain.
AB  - Little is known about the cues controlling the generation of motoneuron
      populations in the mammalian ventral midbrain. We show that Otx2 provides the
      crucial anterior-posterior positional information for the generation of red
      nucleus neurons in the murine midbrain. Moreover, the homeodomain transcription
      factor Nkx6-1 controls the proper development of the red nucleus and of the
      oculomotor and trochlear nucleus neurons. Nkx6-1 is expressed in ventral midbrain
      progenitors and acts as a fate determinant of the Brn3a(+) (also known as Pou4f1)
      red nucleus neurons. These progenitors are partially dorsalized in the absence of
      Nkx6-1, and a fraction of their postmitotic offspring adopts an alternative cell
      fate, as revealed by the activation of Dbx1 and Otx2 in these cells. Nkx6-1 is
      also expressed in postmitotic Isl1(+) oculomotor and trochlear neurons. Similar
      to hindbrain visceral (branchio-) motoneurons, Nkx6-1 controls the proper
      migration and axon outgrowth of these neurons by regulating the expression of at
      least three axon guidance/neuronal migration molecules. Based on these findings,
      we provide additional evidence that the developmental mechanism of the oculomotor
      and trochlear neurons exhibits more similarity with that of special visceral
      motoneurons than with that controlling the generation of somatic motoneurons
      located in the murine caudal hindbrain and spinal cord.

PMID- 19592576
TI  - Differential effects of BMP signaling on parvalbumin and somatostatin interneuron
      differentiation.
AB  - Several different populations of interneurons in the murine cortex, including
      somatostatin (SST)- or parvalbumin (PV)-expressing cells, are born in the ventral
      ganglionic eminences during mid-gestation and then migrate tangentially to the
      cortex. SST is expressed by some interneuron progenitors in the cerebral cortex
      and in migrating populations in the ventrolateral cortex at birth. However, PV
      (also known as PVALB) is not expressed by interneurons until the second postnatal
      week after reaching the cortex, suggesting that molecular cues in the cerebral
      cortex might be involved in the differentiation process. BMP4 is expressed at
      high levels in the somatosensory cortex at the time when the PV(+) interneurons
      differentiate. Treatment of cortical cultures containing interneuron precursors
      is sufficient to generate PV(+) interneurons prematurely and inhibit SST
      differentiation. Furthermore, overexpression of BMP4 in vivo increases the number
      of interneurons expressing PV, with a reduction in the number of SST(+)
      interneurons. PV(+) interneurons in the cortex express BMP type I receptors and a
      subpopulation displays activated BMP signaling, assessed by downstream molecules
      including phosphorylated SMAD1/5/8. Conditional mutation of BMP type I receptors
      in interneuron precursors significantly reduces the number of cortical PV(+)
      interneurons in the adult brain. Thus, BMP4 signaling through type I receptors
      regulates the differentiation of two major medial ganglionic eminence-derived
      interneuron populations and defines their relative numbers in the cortex.

PMID- 19592577
TI  - Functional and phylogenetic analysis shows that Fgf8 is a marker of genital
      induction in mammals but is not required for external genital development.
AB  - In mammalian embryos, male and female external genitalia develop from the genital
      tubercle. Outgrowth of the genital tubercle is maintained by the urethral
      epithelium, and it has been reported that Fgf8 mediates this activity. To test
      directly whether Fgf8 is required for external genital development, we
      conditionally removed Fgf8 from the cloacal/urethral epithelium. Surprisingly,
      Fgf8 is not necessary for initiation, outgrowth or normal patterning of the
      external genitalia. In early genital tubercles, we found no redundant Fgf
      expression in the urethral epithelium, which contrasts with the situation in the
      apical ectodermal ridge (AER) of the limb. Analysis of Fgf8 pathway activity
      showed that four putative targets are either absent from early genital tubercles
      or are not regulated by Fgf8. We therefore examined the distribution of Fgf8
      protein and report that, although it is present in the AER, Fgf8 is undetectable
      in the genital tubercle. Thus, Fgf8 is transcribed, but the signaling pathway is
      not activated during normal genital development. A phylogenetic survey of
      amniotes revealed Fgf8 expression in genital tubercles of eutherian and
      metatherian mammals, but not turtles or alligators, indicating that Fgf8
      expression is neither a required nor a conserved feature of amniote external
      genital development. The results indicate that Fgf8 expression is an early
      readout of the genital initiation signal rather than the signal itself. We
      propose that induction of external genitalia involves an epithelial-epithelial
      interaction at the cloacal membrane, and suggest that the cloacal ectoderm may be
      the source of the genital initiation signal.

PMID- 19592578
TI  - Regulation of cell surface protease matriptase by HAI2 is essential for placental
      development, neural tube closure and embryonic survival in mice.
AB  - Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of
      abnormalities in organogenesis, including organ and digit duplications, atresia,
      fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the
      transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe
      developmental effects of decreased HAI2 activity can be hypothesized to be a
      consequence of excess pericellular proteolytic activity. Indeed, we show here
      that HAI2 is a potent regulator of protease-guided cellular responses, including
      motogenic activity and transepithelial resistance of epithelial monolayers.
      Furthermore, we show that inhibition of the transmembrane serine protease
      matriptase (encoded by St14) is an essential function of HAI2 during tissue
      morphogenesis. Genetic inactivation of the mouse Spint2 gene led to defects in
      neural tube closure, abnormal placental labyrinth development associated with
      loss of epithelial cell polarity, and embryonic demise. Developmental defects
      observed in HAI2-deficient mice were caused by unregulated matriptase activity,
      as both placental development and embryonic survival in HAI2-deficient embryos
      were completely restored by the simultaneous genetic inactivation of matriptase.
      However, neural tube defects were detected in HAI2-deficient mice even in the
      absence of matriptase, although at lower frequency, indicating that the
      inhibition of additional serine protease(s) by HAI2 is required to complete
      neural development. Finally, by genetic complementation analysis, we uncovered a
      unique and complex functional interaction between HAI2 and the related HAI1 in
      the regulation of matriptase activity during development. This study indicates
      that unregulated matriptase-dependent cell surface proteolysis can cause a
      diverse array of abnormalities in mammalian development.

PMID- 19592579
TI  - Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of
      atrioventricular delay.
AB  - The cardiac conduction system comprises a specialized tract of electrically
      coupled cardiomyocytes responsible for impulse propagation through the heart.
      Abnormalities in cardiac conduction are responsible for numerous forms of cardiac
      arrhythmias, but relatively little is known about the gene regulatory mechanisms
      that control the formation of the conduction system. We demonstrate that a distal
      enhancer for the connexin 30.2 (Cx30.2, also known as Gjd3) gene, which encodes a
      gap junction protein required for normal atrioventricular (AV) delay in mice, is
      necessary and sufficient to direct expression to the developing AV conduction
      system (AVCS). Moreover, we show that this enhancer requires Tbx5 and Gata4 for
      proper expression in the conduction system, and Gata4(+/-) mice have short PR
      intervals indicative of accelerated AV conduction. Thus, our results implicate
      Gata4 in conduction system function and provide a clearer understanding of the
      transcriptional pathways that impact normal AV delay.

PMID- 19592580
TI  - Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy:
      precedent for disorders with complex inheritance.
AB  - Microdeletion at chromosomal position 15q13.3 has been described in intellectual
      disability, autism spectrum disorders, schizophrenia and recently in idiopathic
      generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to
      confirm the association of 15q13.3 deletions and IGE. We then set out to
      determine the relative occurrence of sporadic and familial cases and to examine
      the likelihood of having seizures for individuals with the microdeletion in
      familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%)
      unrelated cases of IGE using quantitative PCR or SNP arrays and confirmed by
      array comparative genomic hybridization analysis using probes specific to the
      15q13.3 region. The inheritance of this lesion was tracked using family studies.
      Of the seven microdeletions identified in probands, three were de novo, two were
      transmitted from an unaffected parent and in two cases the parents were
      unavailable. Non-penetrance of the microdeletion was identified in 4/7 pedigrees
      and three pedigrees included other family members with IGE who lacked the 15q13.3
      deletion. The odds ratio is 68 (95% confidence interval 29-181), indicating a
      pathogenic lesion predisposing to epilepsy with complex inheritance and
      incomplete penetrance for the IGE component of the phenotype in multiplex
      families.

PMID- 19592582
TI  - Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide
      new insights into protease activation mechanisms.
AB  - Mutations leading to abrogation of matriptase-2 proteolytic activity in humans
      are associated with an iron-refractory iron deficiency anemia (IRIDA) due to
      elevated hepcidin levels. Here we describe two novel heterozygous mutations
      within the matriptase-2 (TMPRSS6) gene of monozygotic twin girls exhibiting an
      IRIDA phenotype. The first is the frameshift mutation (P686fs) caused by the
      insertion of the four nucleotides CCCC in exon 16 (2172_2173insCCCC) that is
      predicted to terminate translation before the catalytic serine. The second
      mutation is the di-nucleotide substitution c.467C>A and c.468C>T in exon 3 that
      causes the missense mutation A118D in the SEA domain of the extracellular stem
      region of matriptase-2. Functional analysis of both variant matriptase-2
      proteases has revealed that they lead to ineffective suppression of hepcidin
      transcription. We also demonstrate that the A118D SEA domain mutation causes an
      intra-molecular structural imbalance that impairs matriptase-2 activation.
      Collectively, these results extend the pattern of TMPRSS6 mutations associated
      with IRIDA and functionally demonstrate that mutations affecting protease regions
      other than the catalytic domain may have a profound impact in the regulatory role
      of matriptase-2 during iron deficiency.

PMID- 19592581
TI  - Zebrafish survival motor neuron mutants exhibit presynaptic neuromuscular
      junction defects.
AB  - Spinal muscular atrophy (SMA), a recessive genetic disease, affects lower
      motoneurons leading to denervation, atrophy, paralysis and in severe cases death.
      Reduced levels of survival motor neuron (SMN) protein cause SMA. As a first step
      towards generating a genetic model of SMA in zebrafish, we identified three smn
      mutations. Two of these alleles, smnY262stop and smnL265stop, were stop mutations
      that resulted in exon 7 truncation, whereas the third, smnG264D, was a missense
      mutation corresponding to an amino acid altered in human SMA patients. Smn
      protein levels were low/undetectable in homozygous mutants consistent with
      unstable protein products. Homozygous mutants from all three alleles were smaller
      and survived on the basis of maternal Smn dying during the second week of larval
      development. Analysis of the neuromuscular system in these mutants revealed a
      decrease in the synaptic vesicle protein, SV2. However, two other synaptic
      vesicle proteins, synaptotagmin and synaptophysin were unaffected. To address
      whether the SV2 decrease was due specifically to Smn in motoneurons, we tested
      whether expressing human SMN protein exclusively in motoneurons in smn mutants
      could rescue the phenotype. For this, we generated a transgenic zebrafish line
      with human SMN driven by the motoneuron-specific zebrafish hb9 promoter and then
      generated smn mutant lines carrying this transgene. We found that introducing
      human SMN specifically into motoneurons rescued the SV2 decrease observed in smn
      mutants. Our analysis indicates the requirement for Smn in motoneurons to
      maintain SV2 in presynaptic terminals indicating that Smn, either directly or
      indirectly, plays a role in presynaptic integrity.

PMID- 19592583
TI  - Acyl enzyme intermediates in sortase-catalyzed pilus morphogenesis in gram
      positive bacteria.
AB  - In gram-positive bacteria, covalently linked pilus polymers are assembled by a
      specific transpeptidase enzyme called pilus-specific sortase. This sortase is
      postulated to cleave the LPXTG motif of a pilin precursor between threonine and
      glycine and to form an acyl enzyme intermediate with the substrate. Pilus
      polymerization is believed to occur through the resolution of this intermediate
      upon specific nucleophilic attack by the conserved lysine located within the
      pilin motif of another pilin monomer, which joins two pilins with an isopeptide
      bond formed between threonine and lysine. Here, we present evidence for sortase
      reaction intermediates in Corynebacterium diphtheriae. We show that truncated
      SrtA mutants that are loosely bound to the cytoplasmic membrane form high
      molecular-weight complexes with SpaA polymers secreted into the extracellular
      milieu. These complexes are not formed with SpaA pilin mutants that have alanine
      substitutions in place of threonine in the LPXTG motif or lysine in the pilin
      motif. The same phenotype is observed with alanine substitutions of either the
      conserved cysteine or histidine residue of SrtA known to be required for
      catalysis. Remarkably, the assembly of SpaA pili, or the formation of
      intermediates, is abolished with a SrtA mutant missing the membrane-anchoring
      domain. We infer that pilus polymerization involves the formation of covalent
      pilin-sortase intermediates, which occurs within a molecular platform on the
      exoplasmic face of the cytoplasmic membrane that brings together both sortase and
      its cognate substrates in close proximity to each other, likely surrounding a
      secretion apparatus. We present electron microscopic data in support of this
      picture.

PMID- 19592584
TI  - NtcA-regulated heterocyst differentiation genes hetC and devB from Anabaena sp.
      strain PCC 7120 exhibit a similar tandem promoter arrangement.
AB  - Transcription of the hetC gene, whose product is required for heterocyst
      differentiation, takes place from a long promoter region that includes the
      previously described HetR-independent, NtcA-activated promoter producing
      transcripts with a 5' end corresponding to position -571 with respect to the
      translational start site of hetC. Northern blot analysis indicated that the
      accumulation of hetC transcripts depends on HetR, and a second transcriptional
      start site located at position -293 that leads to NtcA-dependent, HetR-dependent
      inducible transcription of hetC was identified. Upon nitrogen stepdown,
      expression of a P(hetC)::gfp fusion was transiently induced in specific cells
      that were differentiating into heterocysts, both when the whole promoter region
      (containing transcription start points -571 and -293) or a short version
      (containing only the transcription start point -293) was used. Expression of hetC
      from the -293 position was delayed in a strain bearing a deleted promoter region
      lacking sequences upstream from position -570. Such a strain was still able to
      differentiate functional heterocysts and to grow diazotrophically, although
      diazotrophic growth was impaired under certain conditions. Similarly, a second,
      NtcA-dependent, HetR-dependent transcriptional start site was identified at
      position -454 in the promoter region upstream from the devBCA operon encoding an
      ABC transport system involved in heterocyst maturation, in which an NtcA
      dependent promoter producing transcripts starting at position -704 had been
      previously noted. Thus, the hetC and devBCA promoter regions exhibit similar
      tandem promoter arrangements.

PMID- 19592585
TI  - The Mycobacterium tuberculosis sigma factor sigmaB is required for full response
      to cell envelope stress and hypoxia in vitro, but it is dispensable for in vivo
      growth.
AB  - The numerous sigma (sigma) factors present in Mycobacterium tuberculosis are
      indicative of the adaptability of this pathogen to different environmental
      conditions. In this report, we describe the M. tuberculosis sigma(B) regulon and
      the phenotypes of an M. tuberculosis sigB mutant strain exposed to cell envelope
      stress, oxidative stress, and hypoxia. The sigB mutant was especially defective
      in survival under hypoxic conditions in vitro, but it was not attenuated for
      growth in THP-1 cells or during mouse and guinea pig infection.

PMID- 19592586
TI  - Swarming of Pseudomonas aeruginosa is controlled by a broad spectrum of
      transcriptional regulators, including MetR.
AB  - Pseudomonas aeruginosa exhibits swarming motility on semisolid surfaces (0.5 to
      0.7% agar). Swarming is a more than just a form of locomotion and represents a
      complex adaptation resulting in changes in virulence gene expression and
      antibiotic resistance. In this study, we used a comprehensive P. aeruginosa PA14
      transposon mutant library to investigate how the complex swarming adaptation
      process is regulated. A total of 233 P. aeruginosa PA14 transposon mutants were
      verified to have alterations in swarming motility. The swarming-associated genes
      functioned not only in flagellar or type IV pilus biosynthesis but also in
      processes as diverse as transport, secretion, and metabolism. Thirty-three
      swarming-deficient and two hyperswarming mutants had transposon insertions in
      transcriptional regulator genes, including genes encoding two-component sensors
      and response regulators; 27 of these insertions were newly identified. Of the 25
      regulatory mutants whose swarming motility was highly impaired (79 to 97%), only
      1 (a PA1458 mutant) had a major defect in swimming, suggesting that this
      regulator might influence flagellar synthesis or function. Twitching motility,
      which requires type IV pili, was strongly affected in only two regulatory mutants
      (pilH and PA2571 mutants) and was moderately affected in three other mutants
      (algR, ntrB, and nosR mutants). Microarray analyses were performed to compare the
      gene expression profile of a swarming-deficient PA3587 mutant to that of the wild
      type PA14 strain under swarming conditions. PA3587 showed 63% homology to metR,
      which encodes a regulator of methionine biosynthesis in Escherichia coli. The
      observed dysregulation in the metR mutant of nine different genes required for
      swarming motility provided a possible explanation for the swarming-deficient
      phenotype of this mutant.

PMID- 19592588
TI  - Characterization of two outer membrane proteins, FlgO and FlgP, that influence
      vibrio cholerae motility.
AB  - Vibrio cholerae is highly motile by the action of a single polar flagellum. The
      loss of motility reduces the infectivity of V. cholerae, demonstrating that
      motility is an important virulence factor. FlrC is the sigma-54-dependent
      positive regulator of flagellar genes. Recently, the genes VC2206 (flgP) and
      VC2207 (flgO) were identified as being regulated by FlrC via a microarray
      analysis of an flrC mutant (D. C. Morris, F. Peng, J. R. Barker, and K. E. Klose,
      J. Bacteriol. 190:231-239, 2008). FlgP is reported to be an outer membrane
      lipoprotein required for motility that functions as a colonization factor. The
      study reported here focuses on the characterization of flgO, the first gene in
      the flgOP operon. We show that FlgO and FlgP are important for motility, as
      strains with mutations in the flgOP genes have reduced motility phenotypes. The
      flgO and flgP mutant populations display fewer motile cells as well as reduced
      numbers of flagellated cells. The flagella produced by the flgO and flgP mutant
      strains are shorter in length than the wild-type flagella, which can be restored
      by inhibiting rotation of the flagellum. FlgO is an outer membrane protein that
      localizes throughout the membrane and not at the flagellar pole. Although FlgO
      and FlgP do not specifically localize to the flagellum, they are required for
      flagellar stability. Due to the nature of these motility defects, we established
      that the flagellum is not sufficient for adherence; rather, motility is the
      essential factor required for attachment and thus colonization by V. cholerae O1
      of the classical biotype. This study reveals a novel mechanism for which the
      outer membrane proteins FlgO and FlgP function in motility to mediate flagellar
      stability and influence attachment and colonization.

PMID- 19592587
TI  - Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does
      not determine bile resistance levels.
AB  - Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose
      roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius
      strains from different sources all harbored a bsh1 allele on their respective
      megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the
      probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of
      two strains that had higher bile resistance levels. Four Bsh1-encoding allele
      groups were identified, defined by truncations or deletions involving a conserved
      residue. In vitro analyses showed that this allelic variation was correlated with
      widely varying bile deconjugation phenotypes. Despite very low activity of the
      UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile
      resistance, both in vitro and during intestinal transit in mice. However, the
      overall bile resistance phenotype of this and other strains was independent of
      the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure
      to bile and cholate identified a multiplicity of stress response proteins and
      putative efflux proteins that appear to broadly compensate for, or mask, the
      effects of allelic variation of bsh genes. Bsh enzymes with different bile
      degrading kinetics, though apparently not the primary determinants of bile
      resistance in L. salivarius, may have additional biological importance because of
      varying effects upon bile as a signaling molecule in the host.

PMID- 19592589
TI  - Role of TonB1 in pyoverdine-mediated signaling in Pseudomonas aeruginosa.
AB  - Pyoverdines are siderophores secreted by Pseudomonas aeruginosa. Uptake of
      ferripyoverdine in P. aeruginosa PAO1 occurs via the FpvA receptor protein and
      requires the energy-transducing protein TonB1. Interaction of (ferri)pyoverdine
      with FpvA activates pyoverdine gene expression in a signaling process involving
      the cytoplasmic-membrane-spanning anti-sigma factor FpvR and the sigma factor
      PvdS. Here, we show that mutation of a region of FpvA that interacts with TonB1
      (the TonB box) prevents this signaling process, as well as inhibiting bacterial
      growth in the presence of the iron-chelating compound ethylenediamine-di(o
      hydroxy-phenylacetic acid). Signaling via wild-type FpvA was also eliminated in
      strains lacking TonB1 but was unaffected in strains lacking either (or both) of
      two other TonB proteins in P. aeruginosa, TonB2 and TonB3. An absence of
      pyoverdine-mediated signaling corresponded with proteolysis of PvdS. These data
      show that interactions between FpvA and TonB1 are required for (ferri)pyoverdine
      signal transduction, as well as for ferripyoverdine transport, consistent with a
      mechanistic link between the signaling and transport functions of FpvA.

PMID- 19592590
TI  - Superdormant spores of Bacillus species have elevated wet-heat resistance and
      temperature requirements for heat activation.
AB  - Purified superdormant spores of Bacillus cereus, B. megaterium, and B. subtilis
      isolated after optimal heat activation of dormant spores and subsequent
      germination with inosine, d-glucose, or l-valine, respectively, germinate very
      poorly with the original germinants used to remove dormant spores from spore
      populations, thus allowing isolation of the superdormant spores, and even with
      alternate germinants. However, these superdormant spores exhibited significant
      germination with the original or alternate germinants if the spores were heat
      activated at temperatures 8 to 15 degrees C higher than the optimal temperatures
      for the original dormant spores, although the levels of superdormant spore
      germination were not as great as those of dormant spores. Use of mixtures of
      original and alternate germinants lowered the heat activation temperature optima
      for both dormant and superdormant spores. The superdormant spores had higher wet
      heat resistance and lower core water content than the original dormant spore
      populations, and the environment of dipicolinic acid in the core of superdormant
      spores as determined by Raman spectroscopy of individual spores differed from
      that in dormant spores. These results provide new information about the
      germination, heat activation optima, and wet-heat resistance of superdormant
      spores and the heterogeneity in these properties between individual members of
      dormant spore populations.

PMID- 19592591
TI  - GidA posttranscriptionally regulates rhl quorum sensing in Pseudomonas
      aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa utilizes two interconnected
      acyl-homoserine lactone quorum-sensing (acyl-HSL QS) systems, LasRI and RhlRI, to
      regulate the expression of hundreds of genes. The QS circuitry itself is
      integrated into a complex network of regulation by other factors. However, our
      understanding of this network is still unlikely to be complete, as a
      comprehensive, saturating approach to identifying regulatory components has never
      been attempted. Here, we utilized a nonredundant P. aeruginosa PA14 transposon
      library to identify additional genes that regulate QS at the level of
      LasRI/RhlRI. We initially screened all 5,459 mutants for loss of function in one
      QS-controlled trait (skim milk proteolysis) and then rescreened attenuated
      candidates for defects in other QS phenotypes (LasA protease, rhamnolipid, and
      pyocyanin production) to exclude mutants defective in functions other than QS. We
      identified several known and novel genes, but only two novel genes, gidA and
      pcnB, affected all of the traits assayed. We characterized gidA, which exhibited
      the most striking QS phenotypes, further. This gene is predicted to encode a
      conserved flavin adenine dinucleotide-binding protein involved in tRNA
      modification. Inactivation of the gene primarily affected rhlR-dependent QS
      phenotypes such as LasA, pyocyanin, and rhamnolipid production. GidA affected
      RhlR protein but not transcript levels and also had no impact on LasR and acyl
      HSL production. Overexpression of rhlR in a gidA mutant partially restored QS
      dependent phenotypes. Taken together, these results indicate that GidA
      selectively controls QS gene expression posttranscriptionally via RhlR-dependent
      and -independent pathways.

PMID- 19592592
TI  - Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria
      gonorrhoeae.
AB  - Type IV pilus expression has been strongly implicated in the virulence of
      Neisseria gonorrhoeae, the causative agent of gonorrhea. In Neisseria, these pili
      undergo frequent antigenic variation (Av), which is presumed to allow reinfection
      of high-risk groups. Pilin Av is the result of RecA-mediated recombination events
      between the gene encoding the major pilin subunit (pilE) and multiple silent
      pilin locus (pilS) copies, utilizing a RecF-like recombination pathway. The role
      of RecBCD in pilin Av has been controversial. Previous studies measuring pilin Av
      in recB and recD mutants in two independent strains of N. gonorrhoeae (MS11 and
      FA1090) by indirect methods yielded conflicting results. In addition, these two
      laboratory strains have been suggested to express very different DNA repair
      capabilities. We show that the FA1090 and MS11 parental strains have similar
      abilities to repair DNA damage via UV-induced DNA damage, nalidixic acid-induced
      double-strand breaks, and methyl methanesulfonate-induced alkylation and that
      RecB and RecD are involved in the repair of these lesions. To test the role of
      the RecBCD pathway in pilin Av, the rate and frequency of pilin Av were directly
      measured by sequencing the pilE locus in randomly selected piliated progeny of
      both MS11 and FA1090 in recB and recD mutants. Our results definitively show that
      recB and recD mutants undergo pilin Av at rates similar to those of the parents
      in both strain backgrounds, demonstrating that efficient pilin Av is neither
      enhanced nor inhibited by the RecBCD complex.

PMID- 19592593
TI  - Hopanoids play a role in membrane integrity and pH homeostasis in
      Rhodopseudomonas palustris TIE-1.
AB  - Sedimentary hopanes are pentacyclic triterpenoids that serve as biomarker proxies
      for bacteria and certain bacterial metabolisms, such as oxygenic photosynthesis
      and aerobic methanotrophy. Their parent molecules, the bacteriohopanepolyols
      (BHPs), have been hypothesized to be the bacterial equivalent of sterols.
      However, the actual function of BHPs in bacterial cells is poorly understood.
      Here, we report the physiological study of a mutant in Rhodopseudomonas palustris
      TIE-1 that is unable to produce any hopanoids. The deletion of the gene encoding
      the squalene-hopene cyclase protein (Shc), which cyclizes squalene to the basic
      hopene structure, resulted in a strain that no longer produced any polycyclic
      triterpenoids. This strain was able to grow chemoheterotrophically,
      photoheterotrophically, and photoautotrophically, demonstrating that hopanoids
      are not required for growth under normal conditions. A severe growth defect, as
      well as significant morphological damage, was observed when cells were grown
      under acidic and alkaline conditions. Although minimal changes in shc transcript
      expression were observed under certain conditions of pH shock, the total amount
      of hopanoid production was unaffected; however, the abundance of methylated
      hopanoids significantly increased. This suggests that hopanoids may play an
      indirect role in pH homeostasis, with certain hopanoid derivatives being of
      particular importance.

PMID- 19592595
TI  - Safety and pharmacokinetics of multiple doses of aclidinium bromide, a novel long
      acting muscarinic antagonist for the treatment of chronic obstructive pulmonary
      disease, in healthy participants.
AB  - Systemic exposure to anticholinergics used for chronic obstructive pulmonary
      disease (COPD) may lead to side effects. This study assessed safety,
      tolerability, and pharmacokinetics of multiple doses of aclidinium bromide, a
      novel, long-acting antimuscarinic. Sixteen healthy participants received
      aclidinium bromide 200, 400, or 800 microg or placebo by dry-powder inhaler for 5
      days, with > or =7 days washout. Aclidinium bromide and metabolite
      pharmacokinetics were assessed. Aclidinium bromide plasma levels were below the
      lower limit of quantification (LLOQ: 0.05 ng/mL) after 200 microg and in most
      participants after 400 microg. Plasma levels in all participants were below the
      LLOQ at all doses, including the highest dose, beyond 1 hour postdose. AUC(0-t)
      and C(max) at steady state were, respectively, 0.08 ng.h/mL and 0.12 ng/mL
      (aclidinium bromide), 0.40 ng.h/mL and 0.14 ng/mL (alcohol metabolite), and 13.47
      ng.h/mL and 2.26 ng/mL (acid metabolite). The t(max) for aclidinium bromide 800
      microg was 15 minutes (first kinetic time point). Adverse event frequency was
      comparable between treatment groups and placebo. The most commonly reported
      adverse events, probably treatment related, were coughing (n = 2) and dysphagia
      (n = 1); 94% of adverse events were mild. These data suggest a low systemic
      bioavailability and favorable safety profile for aclidinium bromide with repeated
      dosing for COPD.

PMID- 19592594
TI  - Comparisons between geographically diverse samples of carried Staphylococcus
      aureus.
AB  - Approximately one-third of the human population is asymptomatically colonized by
      Staphylococcus aureus. However, much of the global diversity within the carriage
      populations remains uncharacterized, and it is unclear to what degree the
      variation is geographically partitioned. We isolated 300 carriage isolates from
      1,531 adults contemporaneously in four countries: France, Algeria, Moldova, and
      Cambodia. All strains were characterized by multilocus sequence typing. Six
      clonal complexes (CCs) were present in all four samples (CC30, -45, -121, -15, 
      5, and -8). Analyses based on the genotype frequencies revealed the French and
      Algerian samples to be most similar and the Cambodian sample to be most distinct.
      While this pattern is consistent with likely rates of human migration and
      geographic distance, stochastic clonal expansion also contributes to regional
      differences. Phylogenetic analysis revealed a highly divergent and
      uncharacterized genotype (ST1223) within Cambodia. This lineage is related to
      CC75, which has previously been observed only in remote aboriginal populations in
      northern Australia.

PMID- 19592596
TI  - High sensitivity of beta-cell replication to the inhibitory effects of
      interleukin-1beta: modulation by adenoviral overexpression of IGF2 in rat islets.
AB  - Interleukin-1beta (IL1B) is an important contributor to the autoimmune
      destruction of beta-cells in type 1 diabetes, and it has been recently related to
      the development of type 2 diabetes. IGF2 stimulates beta-cell proliferation and
      survival. We have determined the effect of IL1B on beta-cell replication, and the
      potential modulation by IGF2 and glucose. Control-uninfected and adenovirus
      encoding for IGF2 (Ad-IGF2)-infected rat islets were cultured at 5.5 or 22.2
      mmol/l glucose with or without 1, 10, 30, and 50 U/ml of IL1B. beta-Cell
      replication was markedly reduced by 10 U/ml of IL1B and was almost nullified with
      30 or 50 U/ml of IL1B. Higher concentrations of IL1B were required to increase
      beta-cell apoptosis. Although IGF2 overexpression had a strong mitogenic effect
      on beta-cells, IGF2 could preserve beta-cell proliferation only in islets
      cultured with 10 U/ml IL1B, and had no effect with 30 and 50 U/ml of IL1B. In
      contrast, IGF2 overexpression induced a clear protection against IL1B-induced
      apoptosis, and higher concentrations of the cytokine were needed to increase beta
      cell apoptosis in Ad-IGF2-infected islets. These results indicate that beta-cell
      replication is highly sensitive to the deleterious effects of the IL1B as shown
      by the inhibition of replication by relatively low IL1B concentrations, and the
      almost complete suppression of beta-cell replication with high IL1B
      concentrations. Likewise, the inhibitory effects of IL-beta on beta-cell
      replication were not modified by glucose, and were only modestly prevented by
      IGF2 overexpression, in contrast with the higher protection against IL1B-induced
      apoptosis afforded by glucose and by IGF2 overexpression.

PMID- 19592597
TI  - Enormous brachio-cephalic arteriovenous fistula aneurysm after renal
      transplantation: case report and review of the literature.
AB  - Creation of arteriovenous fistulae provides readily available vascular access for
      haemodialysis in patients with end-stage renal disease. However, it is associated
      with various potentially serious complications if left unattended. We report a
      case of a 73-year-old male presenting with an enormous brachio-cephalic fistula
      aneurysm measuring 70-5.4 cm 20 years after successful renal transplantation.
      Despite attending regular renal outpatient clinic follow-up, this was only
      noticed as an incidental finding when the patient attended the emergency
      department after a fall that severely bruised his access. The patient
      subsequently underwent ligation with complete removal of the aneurismal fistula
      and discharged to a rehabilitation unit 3 days post-operatively. Systematic
      closure of an arteriovenous fistula should be considered in all patients after
      successful renal transplantation to avoid potentially catastrophic complications
      of an arteriovenous fistula. In patients in whom the closure of vascular access
      is contraindicated, it is crucial to regularly assess the status of any
      arteriovenous fistula when following up patients after renal transplantation.

PMID- 19592598
TI  - Renal disaster relief in Europe: the experience at L'Aquila, Italy, in April
      2009.
AB  - On 6 April 2009, an earthquake struck the city of L'Aquila and the surrounding
      Abruzzo mountains. The disaster left 66,000 people homeless, while 1500 were
      wounded and 298 died. Although Europe as a whole is not so often affected by
      massive earthquakes, Italy is an exception with 12 earthquakes with an intensity
      >6.0 on the Richter scale during the last 100 years. This article offers
      preliminary information on the L'Aquila earthquake. For the time being, nine AKI
      patients who needed dialysis treatment are known. In all of them, kidney function
      recovered. This positive result can be attributed to the efficient and intensive
      rescue efforts coupled to the availability of disaster plans that had been
      developed in advance. This article stresses the importance of (i) advance
      planning of disaster rescue; (ii) the inclusion in these plans of approaches for
      kidney problems and their complications; (iii) the formulation of recommendations
      supporting (para-)medical professionals in their preventive, therapeutic and
      logistic approach to massive incidences of crush.

PMID- 19592599
TI  - Systematic review of antimicrobials for the prevention of haemodialysis catheter
      related infections.
AB  - BACKGROUND: Almost 30% of chronic haemodialysis (HD) patients are dependent on
      central venous catheters (CVCs) for their vascular access, and catheter-related
      bacteraemia (CRB) is the major reason for catheter loss and has been associated
      with substantial morbidity, including meta-static infections. This systematic
      review evaluates the benefits and harms of antimicrobial interventions for the
      prevention of catheter-related infections (CRIs). METHODS: MEDLINE (1950-May
      2009), EMBASE (1980-May 2009) CENTRAL (up to May 2009) and bibliographies of
      retrieved articles were searched for relevant RCTs. Analysis was by a random
      effects model and results expressed as rate ratio, relative risk (RR) and
      weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: A
      total of 29 trials with 2886 patients and 3005 catheters were included.
      Antimicrobial catheter locks (AMLs) significantly reduced the rates of CRBs (rate
      ratio, 0.33, 95% CI 0.24-0.45) and exit-site infections (ESIs) (rate ratio 0.67,
      95% CI 0.47-0.96). Exit-site antimicrobial application also significantly reduced
      the rates of CRBs (rate ratio 0.21, 95% CI 0.12-0.36) and ESIs (rate ratio 0.22,
      95% CI 0.10-0.47). Antimicrobial coating of HD catheters and the use of peri
      operative antimicrobials did not result in significant reduction in rates of CRBs
      and ESIs. CONCLUSION: The use of AMLs and exit-site antimicrobials are useful
      measures in the reduction of CRIs, whereas antimicrobial impregnated catheters
      and peri-operative systemic antimicrobial administration have not been found to
      be beneficial. Further head-to-head trials of various AMLs and exit-site
      antimicrobials are needed to know about their comparative clinical efficacy.

PMID- 19592600
TI  - Monte Carlo determination of the characteristic limits in measurement of ionising
      radiation--fundamentals and numerics.
AB  - It is shown how the decision threshold, the detection limit and the limits of a
      coverage interval - summarily called the characteristic limits - and, in
      addition, the best estimate and the associated standard uncertainty of a non
      negative radiation measurand are to be calculated by using the Monte Carlo (MC)
      method in ionising-radiation measurements. The limits are mathematically defined
      by means of quantiles of the Bayesian distributions of the possible measurand
      values. The MC-induced uncertainties of the limits and typical problems connected
      with MC application are also treated. The paper can serve as a bridge between the
      ISO Guide to the Expression of Uncertainty in Measurement (GUM), Supplement 1
      applying the MC method and ISO/FDIS 11929 (at present in preparation) dealing
      with the characteristic limits. As an illustration, a net count rate measurand,
      being the difference of a gross and a background count rate, is treated
      theoretically and numerically. More complex examples deal with the wipe test for
      surface contamination and with a linear multi-channel spectrum unfolding.

PMID- 19592601
TI  - Family behavior therapy for substance abuse and other associated problems: a
      review of its intervention components and applicability.
AB  - A comprehensive evidence-based treatment for substance abuse and other associated
      problems (Family Behavior Therapy) is described, including its application to
      both adolescents and adults across a wide range of clinical contexts (i.e.,
      criminal justice, child welfare). Relevant to practitioners and applied clinical
      researchers, topic areas include its theoretical and empirical background,
      intervention protocols, methods of enhancing motivation for treatment, and future
      directions.

PMID- 19592602
TI  - Heart rate variability increases with reductions in cigarette smoke exposure
      after 3 days.
AB  - BACKGROUND: Smoking has been shown to influence the tone of the autonomic nervous
      system as reflected by heart rate variability (HRV). To date, no information is
      available as to whether 24-hour HRV might differentiate users of different
      tobacco products. OBJECTIVE: To assess the differences in HRV derived from the 24
      hour electrocardiogram (ECG) following the use of 2 tobacco products of
      potentially different exposures. METHODS: Thirty adult Caucasian male smokers
      (mean age: 42.8 + 5.7 years) smoking 20 to 40 cigarettes/ day were randomized in
      a 3-way crossover study design to either smoke a conventional cigarette (CC, tar:
      11 mg, Nic: 0.8 mg), to use the Electrically Heated Cigarette Smoking System
      (EHCSS: tar: 5 mg, Nic: 0.3 mg, according to the Federal Trade Commission [FTC]),
      or to stop smoking (NS) for 3 days each. The 24 hours ECGs were recorded during
      the last 24 hours of each exposure period. RESULTS: A 24-hour ECG showed highest
      mean values for standard deviation of all normal-to-normal heart beat (NN)
      intervals (SDNN), standard deviation of all 5-minute averaged NN intervals in a
      24-hour period (SDANN), mean of the standard deviations of the NN intervals
      calculated from all 5-minute segments in a 24-hour period (SDNNI), percentage (P)
      of all NN intervals that differ by 50 milliseconds of all NN (PNN50%), the square
      root of the mean of all squared differences between adjacent NN intervals in 24
      hour period (RMSSD), and total number of all NN intervals divided by the height
      of the histogram of all NN intervals measured on a discrete scale with bins of 7
      x 8125 ms (1/128 seconds; HRVTI) when participants stopped smoking followed by
      the use of the reduced exposure product and CC. CONCLUSION: Heart rate
      variability tended to increase with reduced smoke exposure.

PMID- 19592603
TI  - Thumb polydactyly with symphalangism in young children.
AB  - Six cases of young children with thumb polydactyly in which the radial component
      was complicated by symphalangism are reported. Since the symphalangism was
      cartilaginous, plain X-rays showed an apparent joint space. However, its
      continuity was confirmed at surgery. Thumb polydactyly with symphalangism may be
      more common than previously expected.

PMID- 19592604
TI  - Effect of scaphoid and triquetrum excision after limited stabilisation on cadaver
      wrist movement.
AB  - This study assessed the effect of excision of the scaphoid and triquetrum on the
      range of motion of the embalmed cadaver wrist joint after midcarpal
      stabilisation. The range of motion was measured in 12 cadaver wrists before and
      after stabilisation of the joints between the lunate, capitate, triquetrum and
      hamate. This was measured again following resection of the scaphoid and then the
      triquetrum. Scaphoid excision after four-corner stabilisation increased the
      radioulnar (RU) arc by 12 degrees and the flexion-extension (F-E) arc by 10
      degrees. Subsequent excision of the triquetrum, to produce a three-corner
      stabilisation, further increased the RU arc by 7 degrees and the F-E arc by 6
      degrees. Three-corner stabilisation with excision of scaphoid and triquetrum
      improved wrist motion in embalmed cadavers.

PMID- 19592605
TI  - A review of the biomechanics of intrinsic replacement in ulnar palsy.
AB  - The actions of the interossei and lumbricals are many and their loss causes
      significant impairment of hand function. Many procedures have been described to
      restore intrinsic function following ulnar nerve palsy. There are many
      biomechanical issues involved in tendon transfers, including choice of muscle
      tendon unit, route, insertion site, tension and drag. The surgeon, therefore,
      should have a good understanding of biomechanical principles to ensure optimal
      results. In this article the principles of biomechanics are reviewed with
      specific reference to tendon transfers for intrinsic reconstruction in ulnar
      palsy, along with their practical implications.

PMID- 19592606
TI  - The National Children's Study: a golden opportunity to advance the health of
      pregnant women.
AB  - With a $3 billion investment by the federal government, the National Children's
      Study (NCS) recently began recruitment. The NCS is a golden-and potentially
      missed-opportunity to study one of the most underrepresented populations in
      clinical research: pregnant women. As the nation's largest-ever study of
      children's health, the NCS will examine the effects of the environment on
      children from before birth to 21 years of age, with participants sampled
      primarily through women during pregnancy. Thus the NCS presents a rare
      opportunity to study the health of women during and after pregnancy, in addition
      to the health of their children. On both moral and policy grounds, we make the
      case for inclusion of women's health outcomes in the NCS.

PMID- 19592607
TI  - Determinants of left ventricular shear strain.
AB  - Mathematical models of cardiac mechanics can potentially be used to relate
      abnormal cardiac deformation, as measured noninvasively by ultrasound strain rate
      imaging or magnetic resonance tagging (MRT), to the underlying pathology.
      However, with current models, the correct prediction of wall shear strain has
      proven to be difficult, even for the normal healthy heart. Discrepancies between
      simulated and measured strains have been attributed to 1) inadequate modeling of
      passive tissue behavior, 2) neglecting active stress development perpendicular to
      the myofiber direction, or 3) neglecting crossover of myofibers in between
      subendocardial and subepicardial layers. In this study, we used a finite-element
      model of left ventricular (LV) mechanics to investigate the sensitivity of
      midwall circumferential-radial shear strain (E(cr)) to settings of parameters
      determining passive shear stiffness, cross-fiber active stress development, and
      transmural crossover of myofibers. Simulated time courses of midwall LV E(cr)
      were compared with time courses obtained in three healthy volunteers using MRT.
      E(cr) as measured in the volunteers during the cardiac cycle was characterized by
      an amplitude of approximately 0.1. In the simulations, a realistic amplitude of
      the E(cr) signal could be obtained by tuning either of the three model components
      mentioned above. However, a realistic time course of E(cr), with virtually no
      change of E(cr) during isovolumic contraction and a correct base-to-apex gradient
      of E(cr) during ejection, could only be obtained by including transmural
      crossover of myofibers. Thus, accounting for this crossover seems to be essential
      for a realistic model of LV wall mechanics.

PMID- 19592608
TI  - Focus on carbon monoxide: a modulator of neutrophil oxidants and elastase spatial
      localization?

PMID- 19592609
TI  - Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous
      late Na(+) current in the heart.
AB  - Reduction of repolarization reserve increases the risk of arrhythmia. We
      hypothesized that inhibition of K(+) current (I(K)) to decrease repolarization
      reserve would unmask the proarrhythmic role of endogenous, physiological late
      Na(+) current (late I(Na)). Monophasic action potentials (MAP) and 12-lead
      electrocardiogram were recorded from female rabbit isolated hearts. To block I(K)
      and reduce repolarization reserve, E-4031, 4-aminopyridine, and BaCl(2) were
      used; to block endogenous late I(Na), tetrodotoxin (TTX) and ranolazine were
      used. E-4031 (1-60 nM) concentration-dependently prolonged MAP duration
      (MAPD(90)) and increased duration of the T wave from T(peak) to T(end) (T(peak)
      T(end)), transmural dispersion of repolarization (TDR), and beat-to-beat
      variability (BVR) of MAPD(90). E-4031 caused spontaneous and pause-triggered
      polymorphic ventricular tachycardia [torsade de pointes (TdP)]. In the presence
      of 60 nM E-4031, TTX (0.6-3 muM) and ranolazine (5-10 muM) shortened MAPD(90),
      decreased TDR, BVR, and T(peak)-T(end) (n = 9-20, P < 0.01), and abolished
      episodes of TdP. In hearts treated with BaCl(2) or 4-aminopyridine plus E-4031,
      TTX (0.6-3 muM) shortened MAPD(90) and decreased T(peak)-T(end). Ranolazine could
      not reverse the effect of E-4031 to inhibit human ether-a-go-go-related gene
      (HERG) K(+) current; thus, the reversal by ranolazine of effects of E-4031 was
      likely due to inhibition of late I(Na) and not to antagonism of the HERG-blocking
      action of E-4031. We conclude that endogenous, physiological late I(Na)
      contributes to arrhythmogenesis in hearts with reduced repolarization reserve.
      Inhibition of this current partially reverses MAPD prolongation and abolishes
      arrhythmic activity caused by I(K) inhibitors.

PMID- 19592610
TI  - Senescence, apoptosis, and stem cell biology: the rationale for an expanded view
      of intracrine action.
AB  - Some extracellular-signaling peptides also at times function within the
      intracellular space. We have termed these peptides intracrines and have argued
      that intracrine function is associated with a wide variety of peptides/proteins
      including hormones, growth factors, cytokines, enzymes, and DNA-binding proteins
      among others. Here we consider the possibility that intracrines participate in
      the related phenomena of senescence, apoptosis, and stem cell regulation of
      tissue biology. Based on this analysis, we also suggest that the concept of
      intracrine action be expanded to include possible regulatory peptide transfer via
      exosomes/microvesicles and possibly by nanotubes. Moreover, the process of
      microvesicular and nanotube transfer of peptides and other biologically relevant
      molecules, which we inclusively term laterality, is explored. These notions have
      potentially important therapeutic implications, including implications for the
      therapy of cardiovascular disease.

PMID- 19592611
TI  - Absence of gp130 in dopamine beta-hydroxylase-expressing neurons leads to
      autonomic imbalance and increased reperfusion arrhythmias.
AB  - Inflammatory cytokines that act through glycoprotein (gp)130 are elevated in the
      heart after myocardial infarction and in heart failure. These cytokines are
      potent regulators of neurotransmitter and neuropeptide production in sympathetic
      neurons but are also important for the survival of cardiac myocytes after damage
      to the heart. To examine the effect of gp130 cytokines on cardiac nerves, we used
      gp130(DBH-Cre/lox) mice, which have a selective deletion of the gp130 cytokine
      receptor in neurons expressing dopamine beta-hydroxylase (DBH). Basal sympathetic
      parameters, including norepinephrine (NE) content, tyrosine hydroxylase
      expression, NE transporter expression, and sympathetic innervation density,
      appeared normal in gp130(DBH-Cre/lox) compared with wild-type mice. Likewise,
      basal cardiovascular parameters measured under isoflurane anesthesia were similar
      in both genotypes, including mean arterial pressure, left ventricular peak
      systolic pressure, dP/dt(max), and dP/dt(min). However, pharmacological
      interventions revealed an autonomic imbalance in gp130(DBH-Cre/lox) mice that was
      correlated with an increased incidence of premature ventricular complexes after
      reperfusion. Stimulation of NE release with tyramine and infusion of the beta
      agonist dobutamine revealed blunted adrenergic transmission that correlated with
      decreased beta-receptor expression in gp130(DBH-Cre/lox) hearts. Due to the
      developmental expression of the DBH-Cre transgene in parasympathetic ganglia,
      gp130 was eliminated. Cholinergic transmission was impaired in gp130(DBH-Cre/lox)
      hearts due to decreased parasympathetic drive, but tyrosine hydroxylase
      immunohistochemistry in the brain stem revealed that catecholaminergic nuclei
      appeared grossly normal. Thus, the apparently normal basal parameters in
      gp130(DBH-Cre/lox) mice mask an autonomic imbalance that includes alterations in
      sympathetic and parasympathetic transmission.

PMID- 19592612
TI  - Intermedin is a new angiogenic growth factor.
AB  - Intermedin (IMD) is a newly discovered peptide closely related to adrenomedullin.
      We recently reported that IMD gene delivery prevented kidney damage and capillary
      loss in a rat model of chronic renal injury. In this study, we evaluated the role
      of IMD in angiogenesis in the ischemic hindlimb. Adenovirus containing human IMD
      or control adenovirus (Ad.Null) was injected into the adductor muscles of rats
      immediately after femoral artery ligation. The expression of human IMD was
      detected in the skeletal muscle 5 days after the viral injection. Blood perfusion
      in the ischemic hindlimb was monitored by laser-Doppler imaging from 1 to 3 wk
      after gene delivery. When compared with animals receiving Ad.Null, those with IMD
      gene transfer resulted in a time-dependent increase in blood perfusion. IMD gene
      delivery also increased capillary and arteriole density in ischemic hindlimb,
      identified by anti-CD-31 and alpha-smooth muscle actin immunostaining.
      Angiogenesis promoted by IMD was confirmed by increased capillary formation and
      hemoglobin content in Matrigel implants containing IMD peptide in mice. In
      cultured endothelial cells, IMD induced cell migration and tube formation, and
      these effects were blocked by the inhibition of extracellular signal-regulated
      kinase (ERK), Akt, nitric oxide (NO) synthase (NOS), vascular endothelial growth
      factor receptor-2 (VEGFR-2), and anti-IMD-neutralizing antibody. IMD was found to
      increase the phosphorylation of ERK, Akt, and endothelial NOS, as well as to
      augment NO formation, VEGF, and VEGFR-2 synthesis. Taken together, these results
      indicate that IMD enhances angiogenesis through ERK, Akt/NOS/NO, and VEGF/VEGFR-2
      signaling pathways and raises the potential of IMD gene or peptide administration
      in the modulation of endothelial dysfunction.

PMID- 19592613
TI  - Myocardial lysyl oxidase regulation of cardiac remodeling in a murine model of
      diet-induced metabolic syndrome.
AB  - Metabolic syndrome (MetS) represents an increased risk of cardiovascular disease.
      Although its individual components adversely affect cardiac structure and
      function, the extent to which multiple components of MetS affect the cardiac
      extracellular matrix (ECM) has not been well characterized. Lysyl oxidase (LOX)
      is one of the cardiac ECM-modifying enzymes that catalyze the formation of
      collagen cross-linking. Our objective was to define the effect of diet-induced
      MetS on the LOX enzyme. MetS was induced in male C57BL/6 mice by administrating a
      high-fat, high-simple carbohydrate diet for 6 mo. Gene expression was determined
      by real-time PCR. The cardiac protein expression and enzymatic activity of LOX
      were measured. The severity of fibrosis was assessed by histology and
      hydroxylproline assay. Cardiac diastolic function was assessed by in vivo
      analysis of the pressure-volume relationship. LOX, matrix metalloproteinases, and
      their tissue inhibitors were analyzed, and of these three, LOX was most
      significantly changed in the MetS mice. Despite the blunted gene expression of
      LOX isoforms, MetS mice demonstrated a significant upregulation of bone
      morphogenetic protein-1. Correspondingly, there was an increase in the ratio of
      protein expression of mature to proenzyme LOX by 25.9%, enhanced LOX activity by
      50.0%, and increased cardiac cross-linked collagen compared with the controls.
      This fibrotic response coincided with a marked increase in end-diastolic
      pressure, increased left ventricular stiffness, and impaired diastolic filling
      pattern. Our data signify that diet-induced MetS alters the remodeling enzymes,
      mainly LOX, thereby altering ECM structure by increasing the amount of cross
      linking and inducing diastolic dysfunction.

PMID- 19592614
TI  - A(1) adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary
      artery smooth muscle cells.
AB  - The A(1) adenosine receptor (A(1)AR) is coupled to G(i)/G(o) proteins, but the
      downstream signaling pathways in smooth muscle cells are unclear. This study was
      performed in coronary artery smooth muscle cells (CASMCs) isolated from the mouse
      heart [A(1)AR wild type (A(1)WT) and A(1)AR knockout (A(1)KO)] to delineate
      A(1)AR signaling through the PKC pathway. In A(1)WT cells, treatment with (2S)
      N(6)-(2-endo-norbornyl)adenosine (ENBA; 10(-5)M) increased A(1)AR expression by
      150%, which was inhibited significantly by the A(1)AR antagonist 1,3-dipropyl-8
      cyclopentylxanthine (10(-6)M), but not in A(1)KO CASMCs. PKC isoforms were
      identified by Western blot analysis in the cytosolic and membrane fractions of
      cell homogenates of CASMCs. In A(1)WT and A(1)KO cells, significant levels of
      basal PKC-alpha were detected in the cytosolic fraction. Treatment with the
      A(1)AR agonist ENBA (10(-5)M) translocated PKC-alpha from the cytosolic to
      membrane fraction significantly in A(1)WT but not A(1)KO cells. Phospholipase C
      isoforms (betaI, betaIII, and gamma(1)) were analyzed using specific antibodies
      where ENBA treatment led to the increased expression of PLC-betaIII in A(1)WT
      CASMCs while having no effect in A(1)KO CASMCs. In A(1)WT cells, ENBA increased
      PKC-alpha expression and p42/p44 MAPK (ERK1/2) phospohorylation by 135% and 145%,
      respectively. These effects of ENBA were blocked by Go-6976 (PKC-alpha inhibitor)
      and PD-98059 (p42/p44 MAPK inhibitor). We conclude that A(1)AR stimulation by
      ENBA activates the PKC-alpha signaling pathway, leading to p42/p44 MAPK
      phosphorylation in CASMCs.

PMID- 19592615
TI  - The transport of LDL across the deformable arterial wall: the effect of
      endothelial cell turnover and intimal deformation under hypertension.
AB  - A multilayered model of the aortic wall is introduced to investigate the
      transport of low-density lipoprotein (LDL) under hypertension, taking into
      account the influences of increased endothelial cell turnover and deformation of
      the intima at higher pressure. Meanwhile, the thickness and properties of the
      endothelium, intima, internal elastic lamina (IEL), and media are affected by the
      transmural pressure. The LDL macromolecules enter the intima through leaky
      junctions over the endothelium, which are created by dying or dividing cells.
      Water molecules enter the intima via the paracellular pathway through breaks in
      tight junctions after passing the glycocalyx as well as through leaky junctions.
      The glycocalyx is modeled as a Brinkman porous medium to describe the fluid
      filtration associated with its structure. Combined Navier-Stokes and Brinkman
      equations are solved for the transmural flow, and the convective-diffusion
      equation is employed for LDL transport. The permeation of LDL over the surface of
      smooth muscle cells is modeled through a uniform reaction evenly distributed in
      the macroscopically homogeneous media layer. Simulations are performed in an
      axisymmetric plane centered at a leaky cell. The overriding issue addressed is
      that LDL fluxes across the leaky junction, the intima, fenestral pores in the
      IEL, and the media layer are highly affected by the transmural pressure, which
      affects the endothelial cell turnover rate and the compaction of intima. The
      present model, for the first time and with no adjustable parameters, is capable
      of making many realistic predictions including the proper magnitudes for the
      permeability of endothelium and intimal layers and the hydraulic conductivity of
      all layers as well as their trends with pressure. Results for the volume flux
      through the wall and the hydraulic conductivity of the entire arterial wall, the
      endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement
      with previous experimental studies.

PMID- 19592616
TI  - A major role for perifornical orexin neurons in the control of glucose metabolism
      in rats.
AB  - OBJECTIVE: The hypothalamic neuropeptide orexin influences (feeding) behavior as
      well as energy metabolism. Administration of exogenous orexin-A into the brain
      has been shown to increase both food intake and blood glucose levels. In the
      present study, we investigated the role of endogenous hypothalamic orexin release
      in glucose homeostasis in rats. RESEARCH DESIGN AND METHODS: We investigated the
      effects of the hypothalamic orexin system on basal endogenous glucose production
      (EGP) as well as on hepatic and peripheral insulin sensitivity by changing
      orexinergic activity in the hypothalamus combined with hepatic sympathetic or
      parasympathetic denervation, two-step hyperinsulinemic-euglycemic clamps,
      immunohistochemistry, and RT-PCR studies. RESULTS: Hypothalamic disinhibition of
      neuronal activity by the gamma-aminobutyric acid receptor antagonist bicuculline
      (BIC) increased basal EGP, especially when BIC was administered in the
      perifornical area where orexin-containing neurons but not melanocortin
      concentrating hormone-containing neurons were activated. The increased BIC
      induced EGP was largely prevented by intracerebroventricular pretreatment with
      the orexin-1 receptor antagonist. Intracerebroventricular administration of
      orexin-A itself caused an increase in plasma glucose and prevented the daytime
      decrease of EGP. The stimulatory effect of intracerebroventricular orexin-A on
      EGP was prevented by hepatic sympathetic denervation. Plasma insulin clamped at
      two or six times the basal levels did not counteract the stimulatory effect of
      perifornical BIC on EGP, indicating hepatic insulin resistance. RT-PCR showed
      that stimulation of orexin neurons increased the expression of hepatic
      glucoregulatory enzymes. CONCLUSIONS: Hypothalamic orexin plays an important role
      in EGP, most likely by changing the hypothalamic output to the autonomic nervous
      system. Disturbance of this pathway may result in unbalanced glucose homeostasis.

PMID- 19592617
TI  - Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and
      hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance.
AB  - OBJECTIVE: The global epidemic of metabolic syndrome and its complications
      demands rapid evaluation of new and accessible interventions. Insulin resistance
      is the central biochemical disturbance in the metabolic syndrome. The citrus
      derived flavonoid, naringenin, has lipid-lowering properties and inhibits VLDL
      secretion from cultured hepatocytes in a manner resembling insulin. We evaluated
      whether naringenin regulates lipoprotein production and insulin sensitivity in
      the context of insulin resistance in vivo. RESEARCH DESIGN AND METHODS: LDL
      receptor-null (Ldlr(-/-)) mice fed a high-fat (Western) diet (42% calories from
      fat and 0.05% cholesterol) become dyslipidemic, insulin and glucose intolerant,
      and obese. Four groups of mice (standard diet, Western, and Western plus 1% or 3%
      wt/wt naringenin) were fed ad libitum for 4 weeks. VLDL production and parameters
      of insulin and glucose tolerance were determined. RESULTS: We report that
      naringenin treatment of Ldlr(-/-) mice fed a Western diet corrected VLDL
      overproduction, ameliorated hepatic steatosis, and attenuated dyslipidemia
      without affecting caloric intake or fat absorption. Naringenin 1) increased
      hepatic fatty acid oxidation through a peroxisome proliferator-activated receptor
      (PPAR) gamma coactivator 1alpha/PPARalpha-mediated transcription program; 2)
      prevented sterol regulatory element-binding protein 1c-mediated lipogenesis in
      both liver and muscle by reducing fasting hyperinsulinemia; 3) decreased hepatic
      cholesterol and cholesterol ester synthesis; 4) reduced both VLDL-derived and
      endogenously synthesized fatty acids, preventing muscle triglyceride
      accumulation; and 5) improved overall insulin sensitivity and glucose tolerance.
      CONCLUSIONS: Thus, naringenin, through its correction of many of the metabolic
      disturbances linked to insulin resistance, represents a promising therapeutic
      approach for metabolic syndrome.

PMID- 19592618
TI  - Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in
      intracellular reactive oxygen species by upregulating thioredoxin.
AB  - OBJECTIVE: Oxidative stress induced by free fatty acids contributes to the
      development of cardiovascular diseases in patients with metabolic syndrome.
      Reducing oxidative stress may attenuate these pathogenic processes. Activation of
      AMP-activated protein kinase (AMPK) has been reported to reduce intracellular
      reactive oxygen species (ROS) levels. The thioredoxin (Trx) system is a major
      antioxidant system. In this study, we investigated the mechanisms involved in the
      AMPK-mediated regulation of Trx expression and the reduction of intracellular ROS
      levels. RESEARCH DESIGN AND METHODS: We observed that activation of AMPK by 5
      aminoimidazole-4-carboxamide ribonucleotide (AICAR) significantly reduced ROS
      levels induced by palmitic acid in human aortic endothelial cells. Activation of
      AMPK increased expression of the antioxidant Trx, which mediated the ROS
      reduction. RT-PCR showed that AMPK regulated Trx at the transcriptional level.
      RESULTS: Forkhead transcription factor 3 (FOXO3) was identified as the target
      transcription factor involved in the upregulation of Trx expression. FOXO3 bound
      to the Trx promoter, recruited the histone acetylase p300 to the Trx promoter,
      and formed a transcription activator complex, which was enhanced by AICAR
      treatment. AMPK activated FOXO3 by promoting its nuclear translocation. We
      further showed that AICAR injection increased the expression of Trx and decreased
      ROS production in the aortic wall of ApoE-/- mice fed a high-fat diet.
      CONCLUSIONS: These results suggest that activation of the AMPK-FOXO3 pathway
      reduces ROS levels by inducing Trx expression. Thus, the AMPK-FOXO3-Trx axis may
      be an important defense mechanism against excessive ROS production induced by
      metabolic stress and could be a therapeutic target in treating cardiovascular
      diseases in metabolic syndrome.

PMID- 19592619
TI  - Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1.
AB  - OBJECTIVE: Neuropathy is a frequent and severe complication of diabetes. Multiple
      metabolic defects in type 2 diabetic patients result in oxidative injury of
      dorsal root ganglia (DRG) neurons. Our previous work focused on hyperglycemia
      clearly demonstrates induction of mitochondrial oxidative stress and acute injury
      in DRG neurons; however, this mechanism is not the only factor that produces
      neuropathy in vivo. Dyslipidemia also correlates with the development of
      neuropathy, even in pre-diabetic patients. This study was designed to explore the
      contribution of dyslipidemia in neuropathy. RESEARCH DESIGN AND METHODS: Mice (n
      = 10) were fed a control (10% kcal %fat) or high-fat (45% kcal %fat) diet to
      explore the impact of plasma lipids on the development of neuropathy. We also
      examined oxidized lipid-mediated injury in cultured DRG neurons from adult rat
      using oxidized LDLs (oxLDLs). RESULTS: Mice on a high-fat diet have increased
      oxLDLs and systemic and nerve oxidative stress. They develop nerve conduction
      velocity (NCV) and sensory deficits prior to impaired glucose tolerance. In
      vitro, oxLDLs lead to severe DRG neuron oxidative stress via interaction with the
      receptor lectin-like oxLDL receptor (LOX)-1 and subsequent NAD(P)H oxidase
      activity. Oxidative stress resulting from oxLDLs and high glucose is additive.
      CONCLUSIONS: Multiple metabolic defects in type 2 diabetes directly injure DRG
      neurons through different mechanisms that all result in oxidative stress.
      Dyslipidemia leads to high levels of oxLDLs that may injure DRG neurons via LOX-1
      and contribute to the development of diabetic neuropathy.

PMID- 19592620
TI  - Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.
AB  - OBJECTIVE: A number of studies have found that reduced birth weight is associated
      with type 2 diabetes later in life; however, the underlying mechanism for this
      correlation remains unresolved. Recently, association has been demonstrated
      between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1
      and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of
      type 2 diabetes. In order to investigate whether type 2 diabetes risk-conferring
      alleles associate with low birth weight in our Caucasian childhood cohort, we
      examined the effects of 20 such loci on this trait. RESEARCH DESIGN AND METHODS:
      Using data from an ongoing genome-wide association study in our cohort of 5,465
      Caucasian children with recorded birth weights, we investigated the association
      of the previously reported type 2 diabetes-associated variation at 20 loci
      including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B,
      and JAZF1 with birth weight. RESULTS: Our data show that the minor allele of
      rs7756992 (P = 8 x 10(-5)) at the CDKAL1 locus is strongly associated with lower
      birth weight, whereas a perfect surrogate for variation previously implicated for
      the trait at the same locus only yielded nominally significant association (P =
      0.01; r(2) rs7756992 = 0.677). However, association was not detected with any of
      the other type 2 diabetes loci studied. CONCLUSIONS: We observe association
      between lower birth weight and type 2 diabetes risk-conferring alleles at the
      CDKAL1 locus. Our data show that the same genetic locus that has been identified
      as a marker for type 2 diabetes in previous studies also influences birth weight.

PMID- 19592621
TI  - Rac1 is required for cardiomyocyte apoptosis during hyperglycemia.
AB  - OBJECTIVE: Hyperglycemia induces reactive oxygen species (ROS) and apoptosis in
      cardiomyocytes, which contributes to diabetic cardiomyopathy. The present study
      was to investigate the role of Rac1 in ROS production and cardiomyocyte apoptosis
      during hyperglycemia. RESEARCH DESIGN AND METHODS: Mice with cardiomyocyte
      specific Rac1 knockout (Rac1-ko) were generated. Hyperglycemia was induced in
      Rac1-ko mice and their wild-type littermates by injection of streptozotocin
      (STZ). In cultured adult rat cardiomyocytes, apoptosis was induced by high
      glucose. RESULTS: The results showed a mouse model of STZ-induced diabetes, 7
      days of hyperglycemia-upregulated Rac1 and NADPH oxidase activation, elevated ROS
      production, and induced apoptosis in the heart. These effects of hyperglycemia
      were significantly decreased in Rac1-ko mice or wild-type mice treated with
      apocynin. Interestingly, deficiency of Rac1 or apocynin treatment significantly
      reduced hyperglycemia-induced mitochondrial ROS production in the heart.
      Deficiency of Rac1 also attenuated myocardial dysfunction after 2 months of STZ
      injection. In cultured cardiomyocytes, high glucose upregulated Rac1 and NADPH
      oxidase activity and induced apoptotic cell death, which were blocked by
      overexpression of a dominant negative mutant of Rac1, knockdown of gp91(phox) or
      p47(phox), or NADPH oxidase inhibitor. In type 2 diabetic db/db mice,
      administration of Rac1 inhibitor, NSC23766, significantly inhibited NADPH oxidase
      activity and apoptosis and slightly improved myocardial function. CONCLUSIONS:
      Rac1 is pivotal in hyperglycemia-induced apoptosis in cardiomyocytes. The role of
      Rac1 is mediated through NADPH oxidase activation and associated with
      mitochondrial ROS generation. Our study suggests that Rac1 may serve as a
      potential therapeutic target for cardiac complications of diabetes.

PMID- 19592622
TI  - Generation of novel single-chain antibodies by phage-display technology to direct
      imaging agents highly selective to pancreatic beta- or alpha-cells in vivo.
AB  - OBJECTIVE: Noninvasive determination of pancreatic beta-cell mass in vivo has
      been hampered by the lack of suitable beta-cell-specific imaging agents. This
      report outlines an approach for the development of novel ligands homing
      selectively to islet cells in vivo. RESEARCH DESIGN AND METHODS: To generate
      agents specifically binding to pancreatic islets, a phage library was screened
      for single-chain antibodies (SCAs) on rat islets using two different approaches.
      1) The library was injected into rats in vivo, and islets were isolated after a
      circulation time of 5 min. 2) Pancreatic islets were directly isolated, and the
      library was panned in the islets in vitro. Subsequently, the identified SCAs were
      extensively characterized in vitro and in vivo. RESULTS: We report the generation
      of SCAs that bind highly selective to either beta- or alpha-cells. These SCAs are
      internalized by target cells, disappear rapidly from the vasculature, and exert
      no toxicity in vivo. Specific binding to beta- or alpha-cells was detected in
      cell lines in vitro, in rats in vivo, and in human tissue in situ. Electron
      microscopy demonstrated binding of SCAs to the endoplasmatic reticulum and the
      secretory granules. Finally, in a biodistribution study the labeling intensity
      derived from [(125)I]-labeled SCAs after intravenous administration in rats
      strongly predicted the beta-cell mass and was inversely related to the glucose
      excursions during an intraperitoneal glucose tolerance test. CONCLUSIONS: Our
      data provide strong evidence that the presented SCAs are highly specific for
      pancreatic beta-cells and enable imaging and quantification in vivo.

PMID- 19592623
TI  - Hypertriglyceridemic waist phenotype predicts increased visceral fat in subjects
      with type 2 diabetes.
AB  - OBJECTIVE: Greater accumulation of visceral fat is strongly linked to risk of
      cardiovascular disease. However, elevated waist circumference by itself does not
      always identify individuals with increased visceral fat. RESEARCH DESIGN AND
      METHODS: We examined 375 subjects with type 2 diabetes from the CHICAGO cohort
      for presence of hypertriglyceridemic waist phenotype (waist circumference >90 cm
      in men or >85 cm in women, in conjunction with a plasma triglyceride
      concentration of > or =177 mg/dl) to determine its usefulness for identifying
      subjects with increased amounts of visceral fat. We divided subjects into three
      groups: group 1 (low waist circumference and low triglycerides; waist
      circumference < or =90 cm in men or < or =85 cm in women and triglyceride <177
      mg/dl, n = 18), group 2 (high waist circumference and low triglycerides; waist
      circumference >90 cm in men or >85 cm in women and triglycerides <177 mg/dl, n =
      230), and group 3 (high waist circumference and high triglycerides; waist
      circumference >90 cm in men or >85 cm in women and triglycerides > or =177 mg/dl,
      n = 127). RESULTS: Subjects in group 3 had significantly higher visceral fat (P <
      0.0001), A1C (P < 0.01), and coronary artery calcium (P < 0.05) compared with
      group 2, despite similar age, BMI, and waist circumference. The relationship of
      the phenotype to atherosclerosis, however, was attenuated by adjustment for HDL
      cholesterol, triglyceride-rich lipoprotein cholesterol, apolipoprotein B, or LDL
      particle number. CONCLUSIONS: The presence of hypertriglyceridemic waist
      phenotype in subjects with type 2 diabetes identifies a subset with greater
      degree of visceral adiposity. This subset also has greater degree of subclinical
      atherosclerosis that may be related to the proatherogenic lipoprotein changes.

PMID- 19592624
TI  - Effects of exercise training intensity on pancreatic beta-cell function.
AB  - OBJECTIVE: Insulin resistance and beta-cell dysfunction both are important
      contributors to the pathogenesis of type 2 diabetes. Exercise training improves
      insulin sensitivity, but its effects on beta-cell function are less well studied.
      RESEARCH DESIGN AND METHODS: Sedentary, overweight adults were randomized to
      control or one of three 8-month exercise programs: 1) low amount/moderate
      intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous
      intensity. Of 387 randomized, 260 completed the study and 237 had complete data.
      Insulin sensitivity (S(i)), acute insulin response to glucose (AIRg), and the
      disposition index (DI = S(i) x AIRg) were modeled from an intravenous glucose
      tolerance test. RESULTS: Compared with control subjects, all three training
      programs led to increases in DI. However, the moderate-intensity group
      experienced a significantly larger increase in DI than either of the vigorous
      intensity groups and through a different mechanism. The high-amount/vigorous
      intensity group improved S(i) and had a compensatory reduction in AIRg, whereas
      the moderate-intensity group had a similar improvement in S(i) but almost no
      reduction in AIRg. Importantly, the inactive control group experienced a
      significant increase in fasting glucose. CONCLUSIONS: To the extent that the DI
      accurately reflects beta-cell function, we observed that both moderate- and
      vigorous-intensity exercise training improved beta-cell function, albeit through
      distinct mechanisms. It is not clear which of these mechanisms is preferable for
      maintenance of metabolic health. While moderate-intensity exercise led to a
      larger improvement in DI, which may reflect a transition toward a more normal DI,
      longer-term investigations would be necessary to determine which was more
      effective at reducing diabetes risk.

PMID- 19592625
TI  - Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2
      diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly
      dosing.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of incremental
      doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist,
      administered with three dosing schedules in patients with type 2 diabetes
      inadequately controlled with diet and exercise or metformin monotherapy. RESEARCH
      DESIGN AND METHODS: In this randomized multicenter double-blind parallel-group
      study, 356 type 2 diabetic subjects with similar mean baseline characteristics
      (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m(2), A1C 8.0%) received
      subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30,
      or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label
      active reference (per labeling in metformin subjects only) over 16 weeks followed
      by an 11-week washout period. The main outcome measure was change from baseline
      A1C of albiglutide groups versus placebo at week 16. RESULTS: Dose-dependent
      reductions in A1C were observed within all albiglutide schedules. Mean A1C was
      similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg biweekly
      (every 2 weeks), and 100 mg monthly (-0.87, -0.79, and -0.87%, respectively)
      versus placebo (-0.17%, P < 0.004) and exenatide (-0.54%). Weight loss (-1.1 to 
      1.7 kg) was observed with these three albiglutide doses with no significant
      between-group effects. The incidence of gastrointestinal adverse events in
      subjects receiving albiglutide 30 mg weekly was less than that observed for the
      highest biweekly and monthly doses of albiglutide or exenatide. CONCLUSIONS:
      Weekly albiglutide administration significantly improved glycemic control and
      elicited weight loss in type 2 diabetic patients, with a favorable safety and
      tolerability profile.

PMID- 19592626
TI  - Change in the distribution of albuminuria according to estimated glomerular
      filtration rate in Pima Indians with type 2 diabetes.
AB  - OBJECTIVE: We examined secular trends in the frequency distribution of
      albuminuria and estimated glomerular filtration rate (eGFR) in subjects with type
      2 diabetes in 1982-1988 and 2001-2006, two periods associated with major changes
      in the management of diabetes. RESEARCH DESIGN AND METHODS: The cross-sectional
      study included Pima Indians > or =15 years old with type 2 diabetes and measures
      of serum creatinine and urinary albumin-to-creatinine ratios (ACR). The
      continuous probability density distributions of ACR and eGFR were compared for
      the two time periods. eGFR was calculated using the Modification of Diet in Renal
      Disease Study equation. RESULTS: The overall standardized distribution of ACR
      shifted toward lower values between time periods (P = 0.001), whereas the
      standardized distribution of eGFR did not (P = 0.45). In the first period, eGFR
      was <60 ml/min per 1.73 m(2) in 6.5% of the 837 subjects. Of these, 9.3% had
      normal ACR, 7.4% had microalbuminuria, and 83.3% had macroalbuminuria. In the
      second period, the prevalence of low eGFR was similar (6.6% of the 1,310
      subjects). Among those with low eGFR, normal ACR prevalence doubled to 17.2%,
      microalbuminuria prevalence nearly tripled to 19.5%, and macroalbuminuria
      prevalence declined to 63.2%. Twice as many subjects in the second period
      received antihypertensive medicines and 30% more received hypoglycemic medicines
      than in the first period. CONCLUSIONS: The distribution of albuminuria changed
      significantly among diabetic Pima Indians over the past 20 years, as treatment
      with medicines to control hyperglycemia and hypertension increased. The
      distribution of eGFR, however, remained unchanged. Consequently, the frequency of
      chronic kidney disease characterized by normoalbuminuria and low eGFR doubled.

PMID- 19592627
TI  - Hyperglycemia, type 2 diabetes, and depressive symptoms: the British Whitehall II
      study.
AB  - OBJECTIVE: To examine the recent suggestion that impaired fasting glucose may
      protect against depression, whereas a diagnosis of diabetes might then result in
      depression. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of 4,228 adults
      (mean age 60.7 years, 73.0% men) who underwent oral glucose tolerance testing and
      completed the Center for Epidemiologic Studies Depression scale (CES-D). RESULTS:
      After adjustment for demographic factors, health behaviors, and clinical
      measurements (BMI, waist circumference, lipid profile, and blood pressure), there
      was a U-shaped association between fasting glucose and depression (P(curve) =
      0.001), with elevated CES-D at low and very high glucose levels. This finding was
      replicable with 2-h postload glucose (P = 0.11) and A1C (P = 0.007). CONCLUSIONS:
      The U-shaped association between blood glucose and CES-D, with the lowest
      depression risk seen among those in the normoglycemic range of A1C, did not
      support the hypothesized protective effect of hyperglycemia.

PMID- 19592628
TI  - Maternal BMI before pregnancy, maternal weight gain during pregnancy, and risk of
      persistent positivity for multiple diabetes-associated autoantibodies in children
      with the high-risk HLA genotype: the MIDIA study.
AB  - OBJECTIVE: To assess whether maternal BMI before pregnancy and weight gain during
      pregnancy predicted the risk of islet autoimmunity in genetically susceptible
      children. RESEARCH DESIGN AND METHODS: Of 46,939 newborns screened for the high
      risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with
      serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma
      associated protein 2 (IA2). The end point was defined as repeated positivity for
      two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity).
      RESULTS: Thirty-six children developed islet autoimmunity, of whom 10 developed
      type 1 diabetes. Both maternal BMI > or =30 kg/m(2) before pregnancy and maternal
      weight gain > or =15 kg predicted the increased risk of islet autoimmunity
      (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively),
      independent of maternal diabetes. CONCLUSIONS: Maternal weight may predict risk
      of islet autoimmunity in offspring with a high genetic susceptibility for type 1
      diabetes.

PMID- 19592629
TI  - Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2
      diabetes: the Hong Kong diabetes registry.
AB  - OBJECTIVE: LDL cholesterol <2.80 mmol/l was associated with increased cancer risk
      in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol
      and albuminuria and 2) interaction between copresence of these two risk factors
      and statin use for cancer in type 2 diabetes. RESEARCH DESIGN AND METHODS: We
      analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained
      naive for statin treatment and 1,483 patients in whom statin treatment was
      initiated during a median follow-up period of 5.24 years. All patients were free
      of cancer at baseline. Biological interactions were estimated using relative
      excess risk due to interaction (RERI), attributable proportion due to interaction
      (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological
      interaction. RESULTS: In 3,793 statin-naive type 2 diabetic patients, copresence
      of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard
      ratio 2.77 [95% CI 1.78-4.31]) with significant biological interactions (RERI
      1.05 [0.04-2.06]; AP 0.38 [0.09-0.66]). In the whole cohort of 5,276 type 2
      diabetic patients, there was interaction between nonuse of statins and copresence
      of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87
      [0.64-5.09] and AP 0.60 [0.29-0.90]). Statin nonusers with LDL cholesterol <2.80
      mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users
      with or without both risk factors. CONCLUSIONS: In type 2 diabetes, there was
      interaction between low LDL cholesterol and albuminuria with increased cancer
      risks. The latter was attenuated in the presence of statin treatment.

PMID- 19592630
TI  - Insulin-based versus triple oral therapy for newly diagnosed type 2 diabetes:
      which is better?
AB  - OBJECTIVE: Early use of insulin after diagnosis of type 2 diabetes is met with
      resistance because of associated weight gain, hypoglycemia, and fear of decreased
      compliance and quality of life (QoL). RESEARCH DESIGN AND METHODS: In treatment
      naive patients with newly diagnosed type 2 diabetes, insulin and metformin were
      initiated for a 3-month lead-in period, then patients were randomly assigned to
      insulin and metformin (insulin group) or metformin, pioglitazone, and glyburide
      (oral group) for 36 months. Hypoglycemic events, compliance, A1C, weight, QoL,
      and treatment satisfaction were assessed. RESULTS: Of 29 patients randomly
      assigned into each group, 83% (insulin group) and 72% (oral group) completed this
      3-year study. At study completion, A1C was 6.1 +/- 0.6% (insulin group) versus
      6.0 +/- 0.8% (oral group). Weight increased similarly in both groups (P = 0.09)
      by 4.47 kg (95% CI 0.89-8.04 kg) (insulin group) and 7.15 kg (95% CI 4.18-10.13
      kg) (orals group). Hypoglycemic events did not differ between groups (mild 0.51
      event/person-month in the insulin group vs. 0.68 event/person-month in the orals
      group, P = 0.18 and severe 0.04 event/person-year in the insulin group vs. 0.09
      event/person-year in the orals group, P = 0.53). Compliance, QoL, and treatment
      satisfaction were similar between groups, with 100% of patients randomly assigned
      to insulin willing to continue such treatment. CONCLUSIONS: When compared with a
      clinically equivalent treatment regimen, insulin-based therapy is effective and
      did not cause greater weight gain or hypoglycemia nor decrease compliance,
      treatment satisfaction, or QoL. Insulin is safe, well-accepted, and effective for
      ongoing treatment of patients with newly diagnosed type 2 diabetes.

PMID- 19592631
TI  - Diabetes Risk Perception and Intention to Adopt Healthy Lifest yles Among Primary
      Care Patients.
AB  - OBJECTIVE: To examine perceived risk of developing diabetes in primary care
      patients. RESEARCH DESIGN AND METHODS: We recruited 150 nondiabetic primary care
      patients. We made standard clinical measurements, collected fasting blood
      samples, and used the validated Risk Perception Survey for Developing Diabetes
      questionnaire. RESULTS: Patients with high perceived risk were more likely than
      those with low perceived risk to have a family history of diabetes (68 vs. 18%; P
      < 0.0001) and to have metabolic syndrome (53 vs. 35%; P = 0.04). However,
      patients with high perceived risk were not more likely to have intentions to
      adopt healthier lifestyle in the coming year (high 26.0% vs. low 29.2%; P =
      0.69). CONCLUSIONS: Primary care patients with higher perceived risk of diabetes
      were at higher actual risk but did not express greater intention to adopt
      healthier lifestyles. Aspects of health behavior theory other than perceived risk
      need to be explored to help target efforts in the primary prevention of diabetes.

PMID- 19592633
TI  - Association between type of dietary fish and seafood intake and the risk of
      incident type 2 diabetes: the European prospective investigation of cancer (EPIC)
      Norfolk cohort study.
AB  - OBJECTIVE: To investigate the association between fish and seafood intake and new
      onset type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a population-based
      prospective cohort (European Prospective Investigation of Cancer [EPIC]-Norfolk)
      study of men and women aged 40-79 years at baseline (1993-1997). Habitual fish
      and seafood intake (white fish, oily fish, fried fish, and shellfish) was
      assessed using a semiquantitative food frequency questionnaire and categorized as
      less than one or one or more portions/week. During a median (interquartile range)
      follow-up of 10.2 (9.1-11.2) years, there were 725 incident diabetes cases among
      21,984 eligible participants. RESULTS: Higher total fish intake (one or more
      versus less than one portions/week) was associated with a significantly lower
      risk of diabetes (odds ratio [OR] 0.75 [95% CI 0.58-0.96]), in analyses adjusted
      for age, sex, family history of diabetes, education, smoking, physical activity,
      dietary factors (total energy intake, alcohol intake, and plasma vitamin C) and
      obesity (BMI and waist circumference). White fish and oily fish intakes were
      similarly inversely associated with diabetes risk, but the associations were not
      significant after adjustment for dietary factors (oily fish) or obesity (white
      fish). Fried fish was not significantly associated with diabetes risk. Consuming
      one or more portions/week of shellfish was associated with an increased risk of
      diabetes (OR 1.36 [1.02-1.81]) in adjusted analyses. CONCLUSIONS: Total, white,
      and oily fish consumption may be beneficial for reducing risk of diabetes,
      reinforcing the public health message to consume fish regularly. Greater
      shellfish intake seems to be associated with an increased risk of diabetes,
      warranting further investigation into cooking methods and mechanisms.

PMID- 19592632
TI  - Insulin therapy to improve BMI in cystic fibrosis-related diabetes without
      fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy
      trial.
AB  - OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) without fasting hyperglycemia
      (CFRD FH-) is not associated with microvascular or macrovascular complications,
      leading to controversy about the need for treatment. The Cystic Fibrosis Related
      Diabetes Therapy (CFRDT) Trial sought to determine whether diabetes therapy
      improves BMI in these patients. RESEARCH DESIGN AND METHODS: A three-arm
      multicenter randomized trial compared 1 year of therapy with premeal insulin
      aspart, repaglinide, or oral placebo in subjects with cystic fibrosis who had
      abnormal glucose tolerance. RESULTS: One hundred adult patients were enrolled.
      Eighty-one completed the study, including 61 with CFRD FH- and 20 with severly
      impaired glucose tolerance (IGT). During the year before therapy, BMI declined in
      all groups. Among the group with CFRD FH-, insulin-treated patients lost 0.30 +/-
      0.21 BMI units the year before therapy. After 1 year of insulin therapy, this
      pattern reversed, and they gained 0.39 +/- 21 BMI units (P = 0.02). No
      significant change in the rate of BMI decline was seen in placebo-treated
      patients (P = 0.45). Repaglinide-treated patients had an initial significant BMI
      gain (0.53 +/- 0.19 BMI units, P = 0.01), but this effect was not sustained.
      After 6 months of therapy they lost weight so that by 12 months there was no
      difference in the rate of BMI change during the study year compared with the year
      before (P = 0.33). Among patients with IGT, neither insulin nor repaglinide
      affected the rate of BMI decline. No significant differences were seen in the
      rate of lung function decline or the number of hospitalizations in any group.
      CONCLUSIONS: Insulin therapy safely reversed chronic weight loss in patients with
      CFRD FH-.

PMID- 19592634
TI  - Heterogeneous effects of fructose on blood lipids in individuals with type 2
      diabetes: systematic review and meta-analysis of experimental trials in humans.
AB  - OBJECTIVE: Because of blood lipid concerns, diabetes associations discourage
      fructose at high intakes. To quantify the effect of fructose on blood lipids in
      diabetes, we conducted a systematic review and meta-analysis of experimental
      clinical trials investigating the effect of isocaloric fructose exchange for
      carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL
      cholesterol in type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS: We searched
      MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of > or =7
      days. Data were pooled by the generic inverse variance method and expressed as
      standardized mean differences with 95% CI. Heterogeneity was assessed by chi(2)
      tests and quantified by I(2). Meta-regression models identified dose threshold
      and independent predictors of effects. RESULTS: Sixteen trials (236 subjects) met
      the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised
      triglycerides and lowered total cholesterol under specific conditions without
      affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect
      without heterogeneity was seen only in type 2 diabetes when the reference
      carbohydrate was starch (mean difference 0.24 [95% CI 0.05-0.44]), dose was >60
      g/day (0.18 [0.00-0.37]), or follow-up was < or =4 weeks (0.18 [0.00-0.35]).
      Piecewise meta-regression confirmed a dose threshold of 60 g/day (R(2) =
      0.13)/10% energy (R(2) = 0.36). A total cholesterol-lowering effect without
      heterogeneity was seen only in type 2 diabetes under the following conditions: no
      randomization and poor study quality (-0.19 [-0.34 to -0.05]), dietary fat >30%
      energy (-0.33 [-0.52 to -0.15]), or crystalline fructose (-0.28 [-0.47 to 
      0.09]). Multivariate meta-regression analyses were largely in agreement.
      CONCLUSIONS: Pooled analyses demonstrated conditional triglyceride-raising and
      total cholesterol-lowering effects of isocaloric fructose exchange for
      carbohydrate in type 2 diabetes. Recommendations and large-scale future trials
      need to address the heterogeneity in the data.

PMID- 19592635
TI  - Transforming growth factor-beta1 and incident type 2 diabetes: results from the
      MONICA/KORA case-cohort study, 1984-2002.
AB  - OBJECTIVE: Subclinical inflammation leads to insulin resistance and beta-cell
      dysfunction. This study aimed to assess whether levels of circulating
      transforming growth factor-beta1 (TGF-beta1)-a central, mainly immunosuppressive,
      and anti-inflammatory cytokine-were associated with incident type 2 diabetes.
      RESEARCH DESIGN AND METHODS: We measured serum levels of TGF-beta1 from 460
      individuals with and 1,474 individuals without incident type 2 diabetes in a
      prospective case-cohort study within the population-based MONICA (MONItoring of
      Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health
      Research in the Region of Augsburg) cohort. RESULTS: Elevated TGF-beta1
      concentrations were associated with higher, not lower, risk for type 2 diabetes
      (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-beta1
      tertiles: 1.0, 1.08 [0.83-1.42], and 1.41 [1.08-1.83]; P(for) (trend) = 0.012).
      Adjustment for BMI and metabolic and lifestyle factors had virtually no impact on
      the effect size. CONCLUSIONS: Elevated serum concentrations of the cytokine TGF
      beta1 indicate an increased risk for type 2 diabetes. TGF-beta1 may be
      upregulated to counterbalance metabolic and immunological disturbances preceding
      type 2 diabetes.

PMID- 19592637
TI  - Do sedentary older adults benefit from community-based exercise? Results from the
      Active Start program.
AB  - PURPOSE: This study assessed the effectiveness of Active Start, a community-based
      behavior change and fitness program, designed to promote physical activity among
      sedentary community-dwelling older adults. DESIGN AND METHODS: A quasi
      experimental design was used. Data were analyzed using a within-group pretest
      post-test design to calculate changes in the intervention group and changes in
      the waitlist comparison group. Further analyses were conducted after the
      comparison group completed the intervention. Paired t tests were employed to
      analyze unadjusted mean changes in physical performance measures from pretest to
      post-test. Repeated measures analysis of covariance (using SAS Proc Mixed) was
      then conducted to calculate the adjusted mean change for the intervention group.
      RESULTS: Significant improvement was found on all performance measures (strength,
      flexibility, and balance) for the intervention group as a whole. Similar
      improvements were found among subgroups (Whites, African Americans, and
      Hispanics). No significant changes were found in the comparison group when they
      were in the control condition; however, they significantly improved on all
      measures after completing the intervention. IMPLICATIONS: This study suggests
      that a community-based physical activity program benefits sedentary, racially,
      and ethnically diverse older adults by coupling a behavioral change support group
      and fitness classes.

PMID- 19592636
TI  - Casein kinase 2beta as a novel enhancer of activin-like receptor-1 signaling.
AB  - ALK-1 is a transforming growth factor beta (TGF-beta) superfamily receptor that
      is predominantly expressed in endothelial cells and is essential for
      angiogenesis, as demonstrated by the embryonic lethal phentoype when targeted for
      deletion in mice and its mutation in the human disease hereditary hemorrhagic
      telangiectasia. Although ALK-1 and the endothelial-specific TGF-beta superfamily
      coreceptor, endoglin, form a heteromeric complex and bind similar TGF-beta
      superfamily ligands, their signaling mechanisms remain poorly characterized. Here
      we report the identification of CK2beta, the regulatory subunit of protein kinase
      CK2, as a novel enhancer of ALK-1 signaling. The cytoplasmic domain of ALK-1
      specifically binds to CK2beta in vitro and in vivo. NAAIRS mutagenesis studies
      define amino acid sequences 181-199 of CK2beta and 207-212 of ALK-1 as the
      interaction domains, respectively. The ALK-1/CK2beta interaction specifically
      enhanced Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation in
      response to TGF-beta1 and BMP-9 treatment. In a reciprocal manner, siRNA-mediated
      silencing of endogenous CK2beta inhibited TGF-beta1 and BMP-9-stimulated
      Smad1/5/8 phosphorylation and ALK-1-mediated reporter activation. Functionally,
      CK2beta enhanced the ability of activated or ligand-stimulated ALK-1 to inhibit
      endothelial cell migration. Similarly, ALK-1 and CK2beta antagonized endothelial
      tubule formation in Matrigel. These studies support CK2beta as an important
      regulator of ALK-1 signaling and ALK-1-mediated functions in endothelial cells.

PMID- 19592638
TI  - The stigma of hearing loss.
AB  - PURPOSE: To explore dimensions of stigma experienced by older adults with hearing
      loss and those with whom they frequently communicate to target interventions
      promoting engagement and positive aging. DESIGN AND METHODS: This longitudinal
      qualitative study conducted interviews over 1 year with dyads where one partner
      had hearing loss. Participants were naive to or had not worn hearing aids in the
      past year. Data were analyzed using grounded theory, constant comparative
      methodology. RESULTS: Perceived stigma emerged as influencing decision-making
      processes at multiple points along the experiential continuum of hearing loss,
      such as initial acceptance of hearing loss, whether to be tested, type of hearing
      aid selected, and when and where hearing aids were worn. Stigma was related to 3
      interrelated experiences, alterations in self-perception, ageism, and vanity and
      was influenced by dyadic relationships and external societal forces, such as
      health and hearing professionals and media. IMPLICATIONS: Findings are discussed
      in relation to theoretical perspectives regarding stigma and ageism and suggest
      the need to destigmatize hearing loss by promoting its assessment and treatment
      as well as emphasizing the importance of remaining actively engaged to support
      positive physical and cognitive functioning.

PMID- 19592639
TI  - The psychosocial impacts of multimedia biographies on persons with cognitive
      impairments.
AB  - PURPOSE: The purpose of this feasibility pilot project was to observe Alzheimer's
      disease (AD) and mild cognitive impairment (MCI) patients' responses to
      personalized multimedia biographies (MBs). We developed a procedure for using
      digital video technology to construct DVD-based MBs of persons with AD or MCI,
      documented their responses to observing their MBs, and evaluated the psychosocial
      benefits. METHODS: An interdisciplinary team consisting of multimedia biographers
      and social workers interviewed 12 family members of persons with AD and MCI and
      collected archival materials to best capture the families' and patients' life
      histories. We filmed patients' responses to watching the MBs and conducted follow
      up interviews with the families and patients at 3 and 6 months following the
      initial viewing. Qualitative analytic strategies were used for extracting themes
      and key issues identified in both the filmed and the interview response data.
      RESULTS: Analysis of the interview and video data showed how evoked long-term
      memories stimulated reminiscing, brought mostly joy but occasionally moments of
      sadness to the persons with cognitive impairments, aided family members in
      remembering and better understanding their loved ones, and stimulated social
      interactions with family members and with formal caregivers. IMPLICATION: This
      study demonstrates the feasibility of using readily available digital video
      technology to produce MBs that hold special meaning for individuals experiencing
      AD or MCI and their families.

PMID- 19592640
TI  - Localization and characterization of 170 BAC-derived clones and mapping of 94
      microsatellites in the Hessian fly.
AB  - Ninety-four microsatellites from enriched genomic libraries of Hessian fly (Hf,
      Mayetiola destructor [Say]) were localized to 170 cognate clones in an Hf
      bacterial artificial chromosome (BAC) library. These microsatellite-positive BAC
      clones were physically mapped to polytene chromosomes by fluorescent in situ
      hybridization. The mapped microsatellite loci can be used to study the genetic
      diversity and population structure of Hf.

PMID- 19592641
TI  - An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain
      (V50) regulates the persistence of STAT6 phosphorylation.
AB  - Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated
      with atopy in humans; the Q576R and the S503P polymorphisms reside in the
      cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the
      extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on
      signaling remain controversial. To determine the effect of the polymorphisms on
      IL-4 signaling in human cells, we stably transfected the human monocytic cell
      line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the
      P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine
      phosphorylation of STAT6 in response to murine IL-4 treatment similar to the
      induction of tyrosine phosphorylation by human IL-4 signaling through the
      endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6
      rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In
      contrast, STAT6 remained significantly phosphorylated for several hours after
      murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence
      in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA
      expression. Blocking IL-4 signaling during the decay phase using the JAK
      inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of
      phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These
      results indicate that the V50 polymorphism promotes sustained STAT6
      phosphorylation and that this process is mediated by continued engagement of IL
      4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.

PMID- 19592642
TI  - Recurrence of intracranial tumors following adoptive T cell therapy can be
      prevented by direct and indirect killing aided by high levels of tumor antigen
      cross-presented on stromal cells.
AB  - Elimination of peripheral tumors by adoptively transferred tumor-specific T cells
      may require killing of cancer cells and tumor stromal cells. Tumor Ags are cross
      presented on stromal cells, resulting in direct cytotoxic T cell (CTL) killing of
      both Ag-expressing cancer cells and stromal cells. Indirect killing of Ag loss
      variant cells also occurs. We show here that similar processes occur in a brain
      tumor stromal environment. We used murine cancer cell lines that express high or
      low levels of a peptide Ag, SIYRYYGL (SIY), recognized by transgenic 2C CD8(+) T
      cells. The two cell lines are killed with equivalent efficiency by 2C T cells in
      vitro. Following adoptive transfer of 2C T cells into mice with established SIY
      Hi or SIY-Lo brain tumors, tumors of both types regressed, but low-Ag-expressing
      tumors recurred. High-Ag-expressing tumors contained CD11b(+) cells cross
      presenting SIY peptide and were completely eliminated by 2C T cells. To further
      test the role of cross-presentation, RAG1(-/-) H-2(b) mice were infused with H
      2(k) tumor cells expressing high levels of SIY peptide. Adoptively transferred 2C
      T cells are able to kill cross-presenting H-2(b) stromal cells but not H-2(k)
      tumor cells. In peripheral models, this paradigm led to a small static tumor. In
      the brain, activated 2C T cells were able to kill cross-presenting CD11b(+) cells
      and completely eliminate the H-2(k) tumors in most mice. Targeting brain tumor
      stroma or increasing Ag shedding from tumor cells to enhance cross-presentation
      may improve the clinical success of T cell adoptive therapies.

PMID- 19592643
TI  - An engineered GM-CSF-CCL2 fusokine is a potent inhibitor of CCR2-driven
      inflammation as demonstrated in a murine model of inflammatory arthritis.
AB  - CCR2 is a chemokine receptor widely expressed by lymphomyeloid cells involved in
      maladaptive autoimmune ailments. Therefore CCR2 is of great interest as a
      biological target for immune suppression due to its direct implication in
      autoimmune diseases such as rheumatoid arthritis. We have generated a novel
      fusion protein using GM-CSF and an N-terminal truncated version of MCP-1/CCL2 (6
      76, GMME1) and investigated its utility as a CCR2-specific immune suppressor.
      Using BRET studies, we found that distinct to CCL2, GMME1 binding to CCR2 led to
      altered conformational changes in the CCR2 homodimer and did not induce the
      recruitment of beta-arrestin 2 to the receptor. However, CCR2-dependent calcium
      mobilization, BAX induction and caspase-3 activation followed by cell death was
      observed. Using Th17 cells harvested from DBA/1 mice ill with bovine collagen
      induced arthritis, we demonstrate that GMME1 is capable of blocking their
      production of IL-17 in vitro. Upon its delivery to mice symptomatic with
      inflammatory arthritis, a robust clinical recovery occurred with decreased paw
      thickness to normal levels and a significant reduction in anti-collagen Ab titer
      and rheumatoid factor titer, as well as reduction of proinflammatory cytokines
      levels both intraarticular and systemic. Our data demonstrate that GMME1 is a
      powerful synthetic suppressor cytokine that coopts CCR2-dependent cellular
      signaling and blunts the effects of CCR2-expressing lymphomyeloid cells causative
      of autoimmune arthritis.

PMID- 19592644
TI  - Human B cells secrete granzyme B when recognizing viral antigens in the context
      of the acute phase cytokine IL-21.
AB  - Human B cells are currently not known to produce the proapoptotic protease
      granzyme B (GrB) in physiological settings. We have discovered that BCR
      stimulation with either viral Ags or activating Abs in the context of the acute
      phase cytokine IL-21 can induce the secretion of substantial amounts of GrB by
      human B cells. Importantly, GrB response to viral Ags was significantly stronger
      in B cells from subjects recently vaccinated against the corresponding viruses as
      compared with unvaccinated subjects. GrB-secreting B cells featured a homogeneous
      CD19(+)CD20(+)CD27(-)CD38(-)IgD(-) phenotype, improved survival, and enhanced
      expression of costimulatory, Ag-presenting and cell-adhesion molecules. B cell
      derived GrB was enzymatically active and its induction required the activation of
      similar signaling pathways as those in CTLs. Our findings suggest that GrB
      secreting B cells support the early antiviral immune response against viruses
      with endosomal entry pathways, thereby counteracting overwhelming viral
      replication at the beginning of an infection until virus-specific T cells from
      draining lymph nodes arrive at the site of infection. Our data may also explain
      the elevated serum GrB levels found in the early phase of various viral diseases.

PMID- 19592645
TI  - Atypical memory B cells are greatly expanded in individuals living in a malaria
      endemic area.
AB  - Epidemiological observations in malaria endemic areas have long suggested a
      deficiency in the generation and maintenance of B cell memory to Plasmodium
      falciparum (Pf) in individuals chronically reinfected with the parasite.
      Recently, a functionally and phenotypically distinct population of FCRL4(+)
      hyporesponsive memory B cells (MBCs) was reported to be expanded in HIV-infected
      individuals with high viral loads. In this study, we provide evidence that a
      phenotypically similar atypical MBC population is significantly expanded in Pf
      exposed Malian adults and children as young as 2 years of age as compared with
      healthy U.S. adult controls. The number of these atypical MBCs was higher in
      children with chronic asymptomatic Pf infections compared with uninfected
      children, suggesting that the chronic presence of the parasite may drive
      expansion of these distinct MBCs. This is the first description of an atypical
      MBC phenotype associated with malaria. Understanding the origin and function of
      these MBCs could be important in informing the design of malaria vaccines.

PMID- 19592647
TI  - Human CD14+ macrophages in intestinal lamina propria exhibit potent antigen
      presenting ability.
AB  - Intestinal APCs are considered critical in maintaining the balance between the
      response against harmful pathogens and the induction of tolerance to commensal
      bacteria and food Ags. Recently, several studies indicated the presence of gut
      specific APC subsets, which possess both macrophage and dendritic cell (DC)
      markers. These unique APC subsets play important roles in gut immunity,
      especially for immune regulation against commensal bacteria. Herein, we examined
      a unique macrophage subset, which coexpressed the macrophage (Mphi) marker CD14
      and the DC marker CD209 in human intestinal lamina propria (LP). The LP Mphi
      subset in both normal control subjects or Crohn's disease (CD) patients induced
      proliferation of naive CD4(+) T cells as well as monocyte-derived DCs, and it
      expressed retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 and
      retinol dehydrogenase 10, which induced expression of gut homing receptors on T
      cells in a retinoic acid-dependent manner. Moreover, the LP Mphi subset strongly
      evoked differentiation of Th1 cells and slightly induced Th17 cells in both
      normal control subjects and CD patients; the inducing potential was highest in CD
      patients. In CD patients, Th17, but not Th1, induction by the LP Mphi subset was
      enhanced in the presence of commensal bacteria Ags. This enhancement was not
      observed in normal control subjects. The Th17 induction by the LP Mphi subset was
      inhibited by neutralization of IL-6 and IL-1beta, but it was enhanced by blockade
      of retinoic acid signaling. These observations highlight a role for LP Mphi in
      the enhanced Th1, and potentially in Th17 differentiation, at the inflammatory
      site of inflammatory bowel diseases.

PMID- 19592646
TI  - SLP-76 couples Syk to the osteoclast cytoskeleton.
AB  - The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal
      organization, which in turn emanates from signals derived from the
      alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other
      cells, this tyrosine kinase exerts its effects via intermediaries including the
      SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two
      SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas
      cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly
      reducing bone resorption in vitro. Cytoskeletal organization and bone resorption
      are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double
      knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is
      inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation,
      taken with the fact that DKO OCs are rescued by retroviral transduction of only
      SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive
      process. We also find SLP-76 is phosphorylated in a Syk-dependent manner.
      Furthermore, in the absence of the adaptor protein, integrin-mediated
      phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide
      exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3
      association in osteoclastic resorption, retroviral transduction of SLP-76, in
      which the Vav binding site is disrupted (3YF), fails to normalize the
      cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms
      activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3
      dependent manner.

PMID- 19592648
TI  - Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives
      the loss of tolerance in nonobese diabetic mice.
AB  - In humans and NOD mice, defects in immune tolerance result in the spontaneous
      development of type-1-diabetes. Recent studies have ascribed a breakdown in
      tolerance to dysfunction in regulatory T cells that is secondary to reduced IL-2
      production by T cells having the NOD diabetes susceptibility region insulin
      dependent diabetes 3 (Idd3). In this study, we demonstrate a peripheral tolerance
      defect in the dendritic cells of NOD mice that is independent of regulatory T
      cells. NOD CD8 T cells specific for islet Ags fail to undergo deletion in the
      pancreatic lymph nodes. Deletion was promoted by expression of the protective
      alleles of both Idd3 (Il2) and Idd5 in dendritic cells. We further identify a
      second tolerance defect that involves endogenous CD4 T cell expression of the
      disease-promoting NOD alleles of these genetic regions. Pervasive insulitis can
      be reduced by expression of the Idd3 and Idd5 protective alleles by either the Ag
      presenting cell or lymphocytes.

PMID- 19592650
TI  - Deletion of the C-terminal region of dengue virus nonstructural protein 1 (NS1)
      abolishes anti-NS1-mediated platelet dysfunction and bleeding tendency.
AB  - The mechanisms underlying dengue hemorrhagic disease are incompletely understood.
      We previously showed that anti-dengue virus (DV) nonstructural protein 1 (NS1)
      Abs cross-react with human platelets and inhibit platelet aggregation. Based on
      sequence homology alignment, the cross-reactive epitopes reside in the C-terminal
      region of DV NS1. In this study, we compared the effects of Abs against full
      length DV NS1 and NS1 lacking the C-terminal aa 271 to 352 (designated DeltaC
      NS1). Anti-DeltaC NS1 Abs exhibited lower platelet binding activity than that of
      anti-full-length NS1. Anti-full-length NS1 but not anti-DeltaC NS1 Abs inhibited
      platelet aggregation, which was shown to involve integrin alpha(IIb)beta(3)
      inactivation. We found that the bleeding time in full-length NS1-hyperimmunized
      mice was longer than that in the normal control mice. By contrast, DeltaC NS1
      hyperimmunized mice showed a bleeding time similar to that of normal control
      mice. Passively administered anti-DV NS1, but not anti-DeltaC NS1, Ab level
      decreased markedly in serum and this decrease was correlated with Ab binding to
      platelets. A transient platelet loss in the circulation was observed after anti
      DV NS1, but not anti-DeltaC NS1, Ab administration. In summary, platelet
      dysfunction and bleeding tendency are induced by anti-full-length DV NS1 but not
      by anti-DeltaC NS1 Abs. These findings may be important not only for
      understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine
      development.

PMID- 19592649
TI  - Anti-CD40 monoclonal antibody synergizes with CTLA4-Ig in promoting long-term
      graft survival in murine models of transplantation.
AB  - Blockade of the CD40/CD154 signaling pathway using anti-CD154 Abs has shown
      promise in attenuating the alloimmune response and promoting long-term graft
      survival in murine model systems, although side effects observed in humans have
      hampered its progression through clinical trials. Appropriately designed anti
      CD40 Abs may provide a suitable alternative. We investigated two isoforms of a
      novel monoclonal rat anti-mouse CD40 Ab (7E1) for characteristics and effects
      mirroring those of anti-CD154: 7E1-G1 (an IgG1 isotype); and 7E1-G2b (an IgG2b
      isotype). In vitro proliferation assays to measure the agonist properties of the
      two anti-CD40 Abs revealed similar responses when plate bound. However, when
      present as a soluble stimulus, 7E1-G1 but not 7E1-G2b led to proliferation. 7E1
      G2b was as effective as anti-CD154 when administered in vivo in concert with
      CTLA4-Ig in promoting both allogeneic bone marrow chimerism and skin graft
      survival, whereas 7E1-G1 was not. The protection observed with 7E1-G2b was not
      due to depletion of CD40-bearing APCs. These data suggest that an appropriately
      designed anti-CD40 Ab can promote graft survival as well as anti-CD154, making
      7E1-G2b an attractive substitute in mouse models of costimulation blockade-based
      tolerance regimens.

PMID- 19592652
TI  - Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and
      is critical for immunological synapse formation.
AB  - The activation of T cells through the TCR is essential for development of the
      adaptive immune response. TCR does not have any enzymatic activity and relies on
      the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck)
      for initiation of signaling. Here we uncover a mechanism that is responsible for
      plasma membrane targeting of Lck. We show that Lck is transported to the membrane
      via a specific endosomal compartment. The transport depends on the adaptor
      protein Uncoordinated 119 (Unc119), on the GTPase rat brain 11 (Rab11), and on
      the actin cytoskeleton. Unc119 regulates the activation of Rab11. Consequently,
      Unc119 orchestrates the recruitment of the actin-based motor protein, myosin 5B,
      and the organization of multiprotein complexes on endosomes. The Unc119-regulated
      pathway is essential for immunological synapse formation and T cell activation.

PMID- 19592651
TI  - IL-6 is required for airway mucus production induced by inhaled fungal allergens.
AB  - Allergic asthma is caused by inhaled allergens and is characterized by airway
      eosinophilia, as well as mucus hypersecretion, which can lead to airflow
      obstruction. Despite the association of increased IL-6 levels with human atopic
      asthma, the contribution of IL-6 to the development of allergic airway
      inflammation triggered by inhaled allergens remains unclear. In this study, we
      examined the role of IL-6 in a mouse model of allergic airway inflammation
      induced by direct airway exposure to extracts of Aspergillus fumigatus, a common
      allergen in humans. We show that inhaled A. fumigatus extracts rapidly trigger
      the production of IL-6 in the airways. IL-6 appears to be dispensable for the
      recruitment of eosinophils to the lung during the development of allergic airway
      inflammation. However, IL-6 is essential for mucus hypersecretion by airway
      epithelial cells triggered in response to inhaled A. fumigatus Ags. Impaired
      mucus production caused by IL-6 deficiency correlates with a severe reduction in
      the levels of IL-13, a major inducer of mucin glycoproteins. Thus, IL-6 is a key
      regulator of specific hallmark features of allergic airway inflammation and it
      could be a potential target for pulmonary diseases that are associated with
      goblet cell metaplasia and mucus hypersecretion.

PMID- 19592653
TI  - Mast cell-dependent contraction of human airway smooth muscle cell-containing
      collagen gels: influence of cytokines, matrix metalloproteases, and serine
      proteases.
AB  - In asthma, mast cells infiltrate the airway smooth muscle cell layer and secrete
      proinflammatory and profibrotic agents that contribute to airway remodeling. To
      study the effects of mast cell activation on smooth muscle cell-dependent matrix
      contraction, we developed coculture systems of human airway smooth muscle cells
      (HASM) with primary human mast cells derived from circulating progenitors or with
      the HMC-1 human mast cell line. Activation of primary human mast cells by IgE
      receptor cross-linking or activation of HMC-1 cells with C5a stimulated
      contraction of HASM-embedded collagen gels. Contractile activity could be
      transferred with conditioned medium from activated mast cells, implicating
      involvement of soluble factors. Cytokines and proteases are among the agents
      released by activated mast cells that may promote a contractile response. Both IL
      13 and IL-6 enhanced contraction in this model and the activity of IL-13 was
      ablated under conditions leading to expression of the inhibitory receptor IL
      13Ralpha2 on HASM. In addition to cytokines, matrix metalloproteinases (MMPs),
      and serine proteases induced matrix contraction. Inhibitor studies suggested
      that, although IL-13 could contribute to contraction driven by mast cell
      activation, MMPs were critical mediators of the response. Both MMP-1 and MMP-2
      were strongly expressed in this system. Serine proteases also contributed to
      contraction induced by mast cell-activating agents and IL-13, most likely by
      mediating the proteolytic activation of MMPs. Hypercontractility is a hallmark of
      smooth muscle cells in the asthmatic lung. Our findings define novel mechanisms
      whereby mast cells may modulate HASM-driven contractile responses.

PMID- 19592654
TI  - Expression of a CD200 transgene is necessary for induction but not maintenance of
      tolerance to cardiac and skin allografts.
AB  - CD200, a type 2 transmembrane molecule of the Ig supergene family, can induce
      immunosuppression in a number of biological systems, as well as promote increased
      graft acceptance, following binding to its receptors (CD200Rs). Skin and cardiac
      allograft acceptance are readily induced in transgenic mice overexpressing CD200
      under control of a doxycycline-inducible promoter, both of which are associated
      with increased intragraft expression of mRNAs for a number of genes associated
      with altered T cell subset differentiation, including GATA-3, type 2 cytokines
      (IL-4, IL-13), GITR, and Foxp3. Interestingly, some 12-15 days after grafting,
      induction of transgenic CD200 expression can be stopped (by doxycycline
      withdrawal), without obvious significant effect on graft survival. However,
      neutralization of all CD200 expression (including endogenous CD200 expression) by
      anti-CD200 mAb caused graft loss, as did introduction of an acute inflammatory
      stimulus (LPS, 10 microg/mouse, delivered by i.p. injection). We conclude that
      even with apparently stably accepted tissue allografts, disruption of the
      immunoregulatory balance by an intense inflammatory stimulus can cause graft
      loss.

PMID- 19592655
TI  - Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming
      for CD8 T cell effector function and memory.
AB  - A third signal that can be provided by IL-12 or type I IFN is required for
      differentiation of naive CD8 T cells responding to Ag and costimulation. The
      cytokines program development of function and memory within 3 days of initial
      stimulation, and we show here that programming involves regulation of a common
      set of approximately 355 genes including T-bet and eomesodermin. Much of the gene
      regulation program is initiated in response to Ag and costimulation within 24 h
      but is then extinguished unless a cytokine signal is available. Histone
      deacetylase inhibitors mimic the effects of IL-12 or type I IFN signaling,
      indicating that the cytokines relieve repression and allow continued gene
      expression by promoting increased histone acetylation. In support of this,
      increased association of acetylated histones with the promoter loci of granzyme B
      and eomesodermin is shown to occur in response to IL-12, IFN-alpha, or histone
      deacetylase inhibitors. Thus, IL-12 and IFN-alpha/beta enforce in common a
      complex gene regulation program that involves, at least in part, chromatin
      remodeling to allow sustained expression of a large number of genes critical for
      CD8 T cell function and memory.

PMID- 19592656
TI  - Fas apoptosis inhibitory molecule enhances CD40 signaling in B cells and augments
      the plasma cell compartment.
AB  - Fas apoptosis inhibitory molecule (FAIM) was cloned as a mediator of Fas
      resistance that is highly evolutionarily conserved but contains no known effector
      motifs. In this study, we report entirely new functions of FAIM that regulate B
      cell signaling and differentiation. FAIM acts to specifically enhance CD40
      signaling for NF-kappaB activation, IRF-4 expression, and BCL-6 down-regulation
      in vitro, but has no effect on its own or in conjunction with LPS or anti-Ig
      stimulation. In keeping with its effects on IRF-4 and BCL-6, FAIM overexpression
      augments the plasma cell compartment in vivo. These results indicate that FAIM is
      a new player on the field of B cell differentiation and acts as a force
      multiplier for a series of events that begins with CD40 engagement and ends with
      plasma cell differentiation.

PMID- 19592657
TI  - MicroRNA-98 and let-7 confer cholangiocyte expression of cytokine-inducible Src
      homology 2-containing protein in response to microbial challenge.
AB  - Posttranscriptional gene regulation by microRNAs (miRNAs) has been implicated in
      the fine-tuning of TLR-mediated inflammatory response. The cytokine-inducible Src
      homology 2-containing protein (CIS), one member of the suppressors of cytokine
      signaling family of proteins, is an important negative regulator for inflammatory
      cytokine signaling. Using in vitro models using normal human biliary epithelial
      cells (cholangiocytes), we demonstrated that LPS stimulation or infection with
      the parasitic protozoan Cryptosporidium parvum induced expression of CIS protein
      without a change in CIS mRNA levels by activating the TLR signaling pathway. Of
      those miRNAs expressed in cholangiocytes, we found that targeting of the 3'
      untranslated region of CIS by microRNA-98 (miR-98) or let-7 resulted in
      translational repression, but not CIS mRNA degradation. LPS stimulation or C.
      parvum infection decreased cholangiocyte expression of miR-98 and let-7. Down
      regulation of miR-98 and let-7 relieved miRNA-mediated translational suppression
      of CIS and contributed to LPS- and C. parvum-stimulated CIS protein expression.
      Moreover, gain-of-function (by overexpression of CIS) and loss-of-function (by
      siRNA interference) studies revealed that CIS could enhance IkappaBalpha
      degradation and regulate NF-kappaB activation in cholangiocytes in response to
      LPS stimulation or C. parvum infection. Our data suggest that miR-98 and let-7
      confer cholangiocyte expression of CIS in response to microbial challenge, a
      process that may be relevant to the regulation of TLR-mediated epithelial innate
      immune response.

PMID- 19592658
TI  - IFN regulatory factor 4 regulates the expression of a subset of Th2 cytokines.
AB  - Th2 cells can be subdivided into subpopulations depending on the level of a
      cytokine and the subsets of cytokines they produce. We have recently identified
      the ETS family transcription factor PU.1 as regulating heterogeneity in Th2
      populations. To define additional factors that might contribute to Th2
      heterogeneity, we examined the PU.1 interacting protein IFN-regulatory factor
      (IRF)4. When Th2 cells are separated based on levels of IL-10 secretion, IRF4
      expression segregates into the subset of Th2 cells expressing high levels of IL
      10. Infection of total Th2 cells, and IL-10 nonsecreting cells, with retrovirus
      expressing IRF4, resulted in increased IL-4 and IL-10 expression, no change in IL
      5 or IL-13 production and decreased Il9 transcription. Transfection of an IRF4
      specific small interfering RNA into Th2 cells decreases IL-10 production. IRF4
      directly binds the Il10 gene as evidenced by chromatin immunoprecipitation assay,
      and regulates Il10 control elements in a reporter assay. IRF4 interacts with
      PU.1, and in PU.1-deficient T cells there was an increase in IRF4 binding to the
      Il10 gene, and in the ability of IRF4 to induce IL-10 production compared with
      wild-type cells and Il10 promoter activity in a reporter assay. Further
      heterogeneity of IRF4 expression was observed in Th2 cells analyzed for
      expression of multiple Th2 cytokines. Thus, IRF4 promotes the expression of a
      subset of Th2 cytokines and contributes to Th2 heterogeneity.

PMID- 19592660
TI  - Antigen specificity is not required for modulation of lung allergic responses by
      naturally occurring regulatory T cells.
AB  - Naturally occurring Foxp3(+)CD4(+)CD25(+) T cells isolated from lungs of naive
      mice regulate lung allergic airway hyperresponsiveness, inflammation, levels of
      Th2 cytokines, and mucus production. OVA-specific (alphabetaTCR(+)) CD4(+)CD25(+)
      T cells suppressed ragweed-induced airway hyperresponsiveness and inflammation as
      did anti-TCR-treated OVA-specific CD4(+)CD25(+) T cells, suggesting that Ag
      specificity was not required for expression of regulatory activities. Suppression
      was associated with increased levels of IL-10 and TGF-beta; decreased levels of
      IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid; and reduced recruitment
      and activation of CD8(+) T cells in the airways. Following intratracheal
      administration, OVA-specific CD4(+)CD25(+) T cells were identified in both the
      airway lumens and lung parenchyma, and in some instances in close proximity to
      host CD8(+) T cells. These results demonstrate that the regulatory activities of
      naturally occurring Foxp3(+)CD4(+)CD25(+) T cells on lung allergic responses are
      Ag-nonspecific and thus, independent of Ag-specific recognition.

PMID- 19592661
TI  - Intracellular replication-deficient Leishmania donovani induces long lasting
      protective immunity against visceral leishmaniasis.
AB  - No vaccine is currently available for visceral leishmaniasis (VL) caused by
      Leishmania donovani. This study addresses whether a live attenuated centrin gene
      deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and
      protective in animals. LdCen1(-/-) has a defect in amastigote replication both in
      vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites
      in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and
      human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-)
      showed early clearance of virulent parasite challenge not seen in mice immunized
      with heat killed parasites. Upon virulent challenge, the immunized mice displayed
      in the CD4(+) T cell population a significant increase of single and multiple
      cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio.
      Immunized mice also showed increased IgG2a immunoglobulins and NO production in
      macrophages. These features indicated a protective Th1-type immune response. The
      Th1 response correlated with a significantly reduced parasite burden in the
      spleen and no parasites in the liver compared with naive mice 10 wk post
      challenge. Protection was observed, when challenged even after 16 wk post
      immunization, signifying a sustained immunity. Protection by immunization with
      attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-)
      also cross-protected mice against infection with L. braziliensis that causes
      mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and
      effective vaccine candidate against VL as well as mucocutaneous leishmaniasis
      causing parasites.

PMID- 19592659
TI  - A central role for transcription factor C/EBP-beta in regulating CD1d gene
      expression in human keratinocytes.
AB  - CD1d is a nonclassical Ag-presenting molecule that presents glycolipid Ags to NKT
      cells that are involved in immune defense and tumor rejection. It also plays a
      role in immunoregulatory functions in the epidermis. The mechanisms controlling
      the expression of CD1d are not well understood. Therefore, we cloned the CD1d
      gene promoter and characterized its activities in primary human keratinocytes and
      other cell lines of epithelial origin. We found that a CCAAT box in the CD1d
      promoter is required for its expression in keratinocytes. We show here that
      transcription factor C/EBP-beta binds to the CCAAT box in the CD1d promoter in
      vitro and in vivo. Consistent with these observations, deletion of the gene
      encoding for C/EBP-beta caused a loss of CD1d expression. The in vivo regulation
      of CD1d has significant implications for the pathologic mechanisms of certain
      immunologic skin diseases in which NKT cells play a role, such as allergic
      contact dermatitis and psoriasis. Together, these data show a central role for
      C/EBP-beta in regulating CD1d transcription.

PMID- 19592664
TI  - Re: ABO blood group and the risk of pancreatic cancer.

PMID- 19592663
TI  - Palmitoylation-dependent plasma membrane transport but lipid raft-independent
      signaling by linker for activation of T cells.
AB  - Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane
      adaptor protein essential for T cell development and activation. However, whether
      LAT palmitoylation and/or lipid raft localization are required for its function
      is controversial. To address this question, we used a combination of biochemical,
      imaging, and genetic approaches, including LAT retrovirus-transduced mouse T
      cells and bone marrow chimeric mice. A nonpalmitoylated, non-lipid raft-residing
      mutant of transmembrane LAT could not reconstitute T cell development in bone
      marrow chimeric mice. This mutant was absent from the plasma membrane (PM) and
      was restricted mainly to the Golgi apparatus. A chimeric, nonpalmitoylated LAT
      protein consisting of the PM-targeting N-terminal sequence of Src kinase and the
      LAT cytoplasmic domain (Src-LAT) localized as a peripheral membrane protein in
      the PM, but outside lipid rafts. Nevertheless, Src-LAT restored T cell
      development and activation. Lastly, monopalmitoylation of LAT on Cys(26) (but not
      Cys(29)) was required and sufficient for its PM transport and function. Thus, the
      function of LAT in T cells requires its PM, but not raft, localization, even when
      expressed as a peripheral membrane protein. Furthermore, LAT palmitoylation
      functions primarily as a sorting signal required for its PM transport.

PMID- 19592662
TI  - Diminished intracellular invariant chain expression after vaccinia virus
      infection.
AB  - Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and as a
      vaccine for HIV and tumors. However, the immunoevasive properties of VV have
      raised safety concerns. VV infection of APCs perturbs MHC class II-mediated Ag
      presentation. Exposure of human B cell lines to VV induced a substantial
      reduction in cellular expression of the class II chaperone, invariant chain (Ii),
      during the late stages (i.e., 8-10 h) of infection. Yet, cell viability and
      surface expression of MHC class II molecules were maintained up to 24 h after
      exposure to virus. Reductions in Ii and class II mRNA levels were detected as
      early as 6 h after VV infection of APCs. To examine whether VV was acting solely
      to disrupt host protein synthesis, B cells were treated with an inhibitor of
      translation, cycloheximide (CHX). Within 1 h of B cell CHX treatment, Ii protein
      expression decreased coupled with a loss of class II presentation. Analysis of Ii
      degradation in VV- or CHX-treated cells, revealed ongoing Ii proteolysis
      contributing to reduced steady-state Ii levels in these APC. Yet in contrast with
      CHX, VV infection of APCs altered lysosomal protease expression and Ii
      degradation. Virus infection induced cellular cathepsin L expression while
      reducing the levels of other lysosomal proteases. These results demonstrate that
      at late stages of VV infection, reductions in cellular Ii levels coupled with
      changes in lysosomal protease activity, contribute in part to defects in class II
      presentation.

PMID- 19592665
TI  - Structure-activity relationship studies of fostriecin, cytostatin, and key
      analogs, with PP1, PP2A, PP5, and( beta12-beta13)-chimeras (PP1/PP2A and
      PP5/PP2A), provide further insight into the inhibitory actions of fostriecin
      family inhibitors.
AB  - Fostriecin and cytostatin are structurally related natural inhibitors of
      serine/threonine phosphatases, with promising antitumor activity. The total
      synthesis of these antitumor agents has enabled the production of structural
      analogs, which are useful to explore the biological significance of features
      contained in the parent compounds. Here, the inhibitory activity of fostriecin,
      cytostatin, and 10 key structural analogs were tested in side-by-side phosphatase
      assays to further characterize their inhibitory activity against PP1c (Ser/Thr
      protein phosphatase 1 catalytic subunit), PP2Ac (Ser/Thr protein phosphatase 2A
      catalytic subunit), PP5c (Ser/Thr protein phosphatase 5 catalytic subunit), and
      chimeras of PP1 (Ser/Thr protein phosphatase 1) and PP5 (Ser/Thr protein
      phosphatase 5), in which key residues predicted for inhibitor contact with PP2A
      (Ser/Thr protein phosphatase 2A) were introduced into PP1 and PP5 using site
      directed mutagenesis. The data confirm the importance of the C9-phosphate and C11
      alcohol for general inhibition and further demonstrate the importance of a
      predicted C3 interaction with a unique cysteine (Cys(269)) in the beta12-beta13
      loop of PP2A. The data also indicate that additional features beyond the
      unsaturated lactone contribute to inhibitory potency and selectivity. Notably, a
      derivative of fostriecin lacking the entire lactone subunit demonstrated marked
      potency and selectivity for PP2A, while having substantially reduced and similar
      activity against PP1 and PP1/PP2A- PP5/PP2A-chimeras that have greatly increased
      sensitivity to both fostriecin and cytostatin. This suggests that other features
      [e.g., the (Z,Z,E)-triene] also contribute to inhibitory selectivity. When
      considered together with previous data, these studies suggest that, despite the
      high structural conservation of the catalytic site in PP1, PP2A and PP5, the
      development of highly selective catalytic inhibitors should be feasible.

PMID- 19592666
TI  - Endocannabinoids suppress excitatory synaptic transmission to dorsal raphe
      serotonin neurons through the activation of presynaptic CB1 receptors.
AB  - Endocannabinoid signaling in the dorsal raphe (DR) has recently been implicated
      in the regulation of anxiety and depression. However, the cellular mechanisms by
      which endocannabinoids (eCBs) regulate the excitability of DR 5-hydroxytryptamine
      (serotonin; 5-HT) neurons remain poorly understood. In the present study, using
      whole-cell recording from DR 5-HT neurons, we examined the effects of eCBs on
      glutamatergic synapses in the DR. We found that the eCB anandamide decreased the
      amplitude of evoked excitatory postsynaptic currents (eEPSCs). This effect was
      blocked by CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-4-methyl
      1H-pyrazole-3-carboxamide (AM 251) and mimicked by (R)-(+)-[2,3-dihydro-5-methyl
      3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1
      naphthalenylmethanone mesylate (WIN 55,212-2), a CB(1) receptor agonist. The
      inhibition of eEPSC amplitude was associated with an increase in the paired-pulse
      ratio and coefficient of variance. Activation of CB(1) receptors also reduced the
      frequency, but not the amplitude, of miniature excitatory postsynaptic currents,
      indicating that eCBs inhibit glutamate release in the DR. In addition, we found
      that depolarization of DR 5-HT neurons induced a transient inhibition of the
      amplitude of eEPSCs, termed depolarization-induced suppression of excitation
      (DSE). The induction of DSE required an increase in postsynaptic intracellular
      calcium and was due to a decrease in glutamate release. Furthermore,
      pharmacological studies showed that blockade of CB(1) receptors with AM 251
      abolished the DSE. In contrast, activation of CB(1) receptors with WIN 55,212-2
      mimicked and occluded the DSE, indicating that depolarization of DR 5-HT neurons
      triggers eCB release, which in turn mediates the DSE. Together, these results
      indicate that eCBs play a role in modulating glutamatergic synaptic transmission
      to DR 5-HT neurons.

PMID- 19592667
TI  - Synthetic analogs of FTY720 [2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol]
      differentially regulate pulmonary vascular permeability in vivo and in vitro.
AB  - Novel therapies are needed to address the vascular endothelial cell (EC) barrier
      disruption that occurs in inflammatory diseases such as acute lung injury (ALI).
      We previously demonstrated the potent barrier-enhancing effects of both
      sphingosine 1-phosphate (S1P) and the structurally similar compound FTY720 [2
      amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol] in inflammatory lung injury. In
      this study, we examined the therapeutic potential of several novel FTY720 analogs
      to reduce vascular leak. Similar to S1P and FTY720, the (R)- and (S)-enantiomers
      of FTY720 phosphonate and enephosphonate analogs produce sustained EC barrier
      enhancement in vitro, as seen by increases in transendothelial electrical
      resistance (TER). In contrast, the (R)- and (S)-enantiomers of FTY720
      regioisomeric analogs disrupt EC barrier integrity in a dose-dependent manner.
      Barrier-enhancing FTY720 analogs demonstrate a wider protective concentration
      range in vitro (1-50 microM) and greater potency than either S1P or FTY720. In
      contrast to FTY720-induced EC barrier enhancement, S1P and the FTY720 analogs
      dramatically increase TER within minutes in association with cortical actin ring
      formation. Unlike S1P, these FTY720 analogs exhibit differential phosphorylation
      effects without altering the intracellular calcium level. Inhibitor studies
      indicate that barrier enhancement by these analogs involves signaling via G(i)
      coupled receptors, tyrosine kinases, and lipid rafts. Consistent with these in
      vitro responses, the (S)-phosphonate analog of FTY720 significantly reduces
      multiple indices of alveolar and vascular permeability in a lipopolysaccharide
      mediated murine model of ALI (without significant alterations in leukocyte
      counts). These results demonstrate the capacity for FTY720 analogs to
      significantly decrease pulmonary vascular leakage and inflammation in vitro and
      in vivo.

PMID- 19592669
TI  - The problematic placebo.

PMID- 19592668
TI  - Sequence-based analysis of protein energy landscapes reveals nonuniform thermal
      adaptation within the proteome.
AB  - Thermal adaptation of individual proteins is often achieved through modulating
      protein stability, with proteins that are adapted to extreme cold environments
      having increased conformational flexibility when brought to mesophilic
      conditions. Conversely, proteins adapted to higher temperatures appear less
      dynamic and are found to be much more stable against thermal denaturation than
      their mesophilic counterparts. According to the current paradigm, the adaptation
      of an organism for survival at higher or lower temperatures is facilitated by the
      adaptation of the component proteins. We note, however, that these observations
      have been carried out on relatively few proteins. The extent to which the
      conformational stabilities of all members of the proteome have been modulated for
      thermal adaptation remains unclear, with no direct experimental strategies to
      address this issue. Adapted extremophilies are likely to use a multitude of
      molecular and biophysical strategies for survival and, therefore, evolution of
      specific biophysical properties of proteins for optimal function may not be
      necessary for all proteins in the proteome. Using a sequence-based predictor of
      protein stability, eScape, an in silico examination of several extremophilic
      proteomes shows a correlation between the collective stability of the proteins
      and the thermal range of survival for the organism as expected. Unexpectedly,
      however, the analysis shows that protein thermostability is modified to different
      extents across the proteome and depends on the functional role for which the
      protein is involved. Identification of these differences provides unique
      opportunities to study interdependence within the proteome as well as the role
      that the proteome plays in the process of evolutionary thermal adaptation.

PMID- 19592671
TI  - Repression of aryl hydrocarbon receptor transcriptional activity by epidermal
      growth factor.
AB  - The aryl hydrocarbon receptor (AHR) mediates most, if not all, of the many
      toxicological effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-
      p-dioxin [(TCDD) or dioxin]. The "classical" pathway of AHR action involves
      dimerization of the liganded AHR with the aryl hydrocarbon nuclear translocator
      (ARNT) protein, and the AHR-ARNT dimer specifically associates with the enhancer
      regions of dioxin-responsive genes, leading to their increased transcription.
      Sutter and coworkers recently reported that epidermal growth factor (EGF)
      represses the dioxin-mediated induction of CYP1A1 in cultured normal human
      keratinocytes by inhibiting the recruitment of the transcriptional coactivator
      protein p300 to the CYP1A1 gene. EGF also inhibits the dioxin-dependent induction
      of certain parameters in keratinocytes that are reflective of dioxin-induced
      chloracne. These findings point to the potential usefulness of EGF for the
      treatment of chloracne and also describe a novel mechanism for repression of
      dioxin-induced gene transcription.

PMID- 19592673
TI  - Orthosteric/allosteric bitopic ligands: going hybrid at GPCRs.
AB  - G protein-coupled receptors (GPCRs) can adopt multiple biologically active states
      that can be differentially stabilized by ligands that bind to topographically
      distinct sites (e.g., orthosteric ligands and allosteric modulators). Recent
      studies in the field are now demonstrating the utility of linking orthosteric and
      allosteric pharmacophores to yield hybrid, or bitopic, ligands, with improved
      affinity and/or receptor subtype selectivity. Interestingly, this approach can
      also engender functional selectivity in the actions of orthosteric ligands,
      highlighting a viable means of further sculpting GPCR ligand responses. Indeed,
      some previously identified functionally selective agonists may actually represent
      hitherto unappreciated bitopic ligands.

PMID- 19592672
TI  - Designing immunotherapies to thwart drug abuse.
AB  - Immunotherapy for treating illicit drug abuse is a rapidly advancing field. There
      are currently two major approaches to developing drug-specific immunotherapies:
      active and passive. Active immunotherapy involves conjugating a drug-like hapten
      to a carrier protein and using traditional immunization approaches to generate a
      drug-specific immune response in the patient. In contrast, passive immunotherapy
      utilizes preformed monoclonal antibodies. Whether generated by active
      immunization or delivered passively, antibodies act as pharmacokinetic
      antagonists by binding the drug in the blood-stream and reducing the amount and
      rate of drug delivery to receptors in the brain. A newly emerging technology in
      anti-drug immunotherapy is the use of antibody fragments, or scFvs, rather than
      intact immunoglobulin G (IgG). These scFvs can retain the same binding properties
      as the original mAbs, and are onethird the molecular weight, providing a scaffold
      for creating antibody treatments with more customizable properties. Another
      nascent area of research utilizing the scFv scaffold is in creating drug-specific
      scFv-nanoparticle conjugates. These conjugates could improve upon current drug
      specific antibody paradigms by increasing multivalency and allowing
      pharmacokinetic customization, while avoiding interactions with endogenous
      antibody receptor pathways. These parallel approaches to immunotherapy are moving
      rapidly toward the clinic and may soon provide new therapies for treating drug
      abuse.

PMID- 19592674
TI  - Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the
      power of combination knockout mice.
AB  - A TP-binding cassette (ABC) multidrug transporters are cellular efflux pumps with
      broad and often widely overlapping substrate specificities. They can have a major
      impact on the pharmacokinetics and hence overall pharmacological behavior of many
      drugs. To study their separate roles and functional overlap, or complementarity,
      a collection of mice deficient in two or more ABC transporters has been
      generated. This review discusses recent findings obtained with these models,
      focusing on pharmacokinetic studies with a number of clinically relevant drugs.
      In addition, the characterization of these mice and some physiological aspects of
      ABC multidrug transporters are addressed.

PMID- 19592675
TI  - Emotion locomotion: promoting the emotional health of elementary school children
      by recognizing emotions.
AB  - Emotion recognition is a critical life skill children need for mental health
      promotion to meet the complexities and challenges of growing up in the world
      today. Five nursing students and their instructor designed Emotion Locomotion, a
      program for children ages 6-8 during a public health nursing practicum for an
      inner-city parochial school. Emotion Locomotion used an analogy that the "engine"
      of a train represents the "individual" and the train "cars" represent various
      emotions, such as happiness, sadness, calmness, and anger. Analysis of pre- and
      posttest scores showed an increase in appropriate student responses that involved
      identifying emotions from photographs and in recognition of vocabulary words
      representing emotions. Students' role playing during puppet shows demonstrated
      increased appropriate expression of emotions and healthy ways to deal with
      feelings during scenarios. Programs such as Emotion Locomotion present
      opportunities to expand the outreach of school nurses and colleges of nursing
      through community partnerships to provide critical life skills for student
      populations.

PMID- 19592676
TI  - Head injuries in children.
AB  - School nurses play a crucial role in injury prevention and initial treatment when
      injuries occur at school. The role of school nurses includes being knowledgeable
      about the management of head injuries, including assessment and initial
      treatment. The school nurse must be familiar with the outcomes of a head injury
      and know when further evaluation is indicated. Developing a head injury protocol
      in the school setting is one strategy to make sure that all involved are able to
      consistently and effectively respond to a head injury and prevent a possible
      negative outcome. The combination of a protocol, nursing judgment, and best
      practices can ensure that all means are used to take care of children when a head
      injury is sustained. These strategies will help to increase the safety of
      children at school. A systematic approach to the management of these types of
      injuries is essential for preventing possible complications.

PMID- 19592677
TI  - Balance across contexts: importance of balanced need satisfaction across various
      life domains.
AB  - Self-determination theory posits that satisfaction of three basic psychological
      needs-autonomy, competence, and relatedness-are required for psychological well
      being, and a recent study showed that the balance in the satisfaction of these
      three needs independently affects well-being. The present investigation builds on
      these findings by examining the balance of adolescents' need satisfaction across
      distinct life contexts. The results of three studies show that adolescents who
      experience a balance of need satisfaction across important life contexts,
      including at school, at home, with friends, and in part-time jobs, reported
      higher well-being and better school adjustment. This finding emerged consistently
      across four countries and across multiple measures of school adjustment,
      including teacher reports. Together, these results support previous research that
      highlights the importance of consistency for psychological functioning.

PMID- 19592678
TI  - Altering category-level beliefs: the impact of level of representation at belief
      formation and belief disconfirmation.
AB  - This research program investigates whether representational level of information
      underlying initial beliefs (individual vs. category) and disconfirming
      information (individual vs. category) influence the magnitude of belief and
      attitude change regarding categories of objects. In 3 experiments, 2 key effects
      emerged. A main effect of type of disconfirming information indicated that
      category-level information produced more belief and attitude change than did
      individual-level information. Also, a significant interaction between type of
      information at formation and disconfirmation indicated a relative matching
      effect, with category-level disconfirmation producing substantially more belief
      and attitude change than individual-level disconfirmation when initial beliefs
      were based on category-level information but only slightly greater change when
      initial beliefs were based on individual-level information.

PMID- 19592679
TI  - Outwardly rectifying anionic channel from the plasma membrane of the fungus
      Phycomyces blakesleeanus.
AB  - In the present report, by using a patch clamp technique, we provide, to our
      knowledge, the first detailed description of an anionic channel from filamentous
      fungi. The characterized channel, an outwardly rectifying anionic channel (ORAC),
      is the most prominent feature of the cell membrane of the fungus Phycomyces
      blakesleeanus in the absence of energizing substrates. The unitary conductance of
      the channel is 11.3 +/- 0.4 pS. It is characterized by a strong voltage
      dependence of the open-channel probability (zdelta; the gating charge is 2.1 +/-
      0.1), and the channel is activated by depolarization. The values of the time
      constants for voltage-induced activation and deactivation of 28 +/- 3 ms for
      tau(a) and 39 +/- 9 ms for tau(d) show that the ORAC is characterized by fast
      activation/deactivation kinetics. The ORAC shows strong selectivity for anions
      over cations and weak selectivity among anions, with a selectivity sequence of I(
      ) >or= NO(3)(-) > Br(-) > Cl(-) > SO(4)(2-) = 4.8 > 4.4 > 2.2 > 1 > 0.55, which
      corresponds to Eisenman series 1. The channel is characterized by two open and
      two closed states, with dominant long open (tau(o2) = 35.0 +/- 3.9 ms) and long
      closed (tau(c2) = 166 +/- 28 ms) states occupying 63% +/- 8% and 79% +/- 3% of
      total open and closed times, respectively. The ORAC is insensitive to anthracene
      9-carboxylic acid (<200 microM), but 2 mM malate reversibly inhibits 59% +/- 12%
      of the channel activity. Based on the electrophysiological properties of the
      channel, we propose that the ORAC plays a role in anion accumulation and in
      membrane potential regulation through local membrane depolarization.

PMID- 19592680
TI  - High-resolution mapping and analysis of copy number variations in the human
      genome: a data resource for clinical and research applications.
AB  - We present a database of copy number variations (CNVs) detected in 2026 disease
      free individuals, using high-density, SNP-based oligonucleotide microarrays. This
      large cohort, comprised mainly of Caucasians (65.2%) and African-Americans
      (34.2%), was analyzed for CNVs in a single study using a uniform array platform
      and computational process. We have catalogued and characterized 54,462 individual
      CNVs, 77.8% of which were identified in multiple unrelated individuals. These
      nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9%
      of the genome; 51.5% of these were previously unreported, and >85% are rare. Our
      annotation and analysis confirmed and extended previously reported correlations
      between CNVs and several genomic features such as repetitive DNA elements,
      segmental duplications, and genes. We demonstrate the utility of this data set in
      distinguishing CNVs with pathologic significance from normal variants. Together,
      this analysis and annotation provides a useful resource to assist with the
      assessment of CNVs in the contexts of human variation, disease susceptibility,
      and clinical molecular diagnostics.

PMID- 19592683
TI  - A rare cause of upper GI bleeding.

PMID- 19592682
TI  - Dermatological complications and safety of anti-TNF treatments.

PMID- 19592681
TI  - Unusual composition of a yeast chromosome arm is associated with its delayed
      replication.
AB  - The 11.3-Mb genome of the yeast Lachancea (Saccharomyces) kluyveri displays an
      intriguing compositional heterogeneity: a region of approximately 1 Mb, covering
      almost the whole left arm of chromosome C (C-left), has an average GC content of
      52.9%, which is significantly higher than the 40.4% global GC content of the rest
      of the genome. This region contains the MAT locus, which remains normal in
      composition. The excess of GC base pairs affects both coding and noncoding
      sequences, and thus is not due to selective pressure acting on protein sequences.
      It leads to a strong codon usage bias and alters the amino acid composition of
      the 457 proteins encoded on C-left that do not show obvious bias for functional
      categories, or the presence of paralogs or orthologs of essential genes of
      Saccharomyces cerevisiae. They share significant synteny conservation with other
      species of the Saccharomycetaceae, and phylogenetic analysis indicates that C
      left originates from a Lachancea species. In contrast, there is a complete
      absence of transposable elements in C-left, whereas 18 elements per megabase are
      distributed across the rest of the genome. Comparative hybridization of
      synchronized cells using high-density genome arrays reveals that C-left is
      replicated later during S phase than the rest of the genome. Two possible primary
      causes of this major compositional heterogeneity are discussed: an ancient
      hybridization of two related species with very distinct GC composition, or an
      intrinsic mechanism, possibly associated with the loss of the silent cassettes
      from C-left that progressively increased the GC content and generated the delayed
      replication of this chromosomal arm.

PMID- 19592684
TI  - Submucosal tumour in a young girl.

PMID- 19592685
TI  - Mechanisms underlying dysphagia in eosinophilic oesophagitis.

PMID- 19592686
TI  - Myenteric plexitis in enteric dysmotility: what are the implications for clinical
      practice?

PMID- 19592687
TI  - Probiotic carbohydrates reduce intestinal permeability and inflammation in
      metabolic diseases.

PMID- 19592688
TI  - Drugs, ligation or both for the prevention of variceal rebleeding?

PMID- 19592689
TI  - Unusual complications of acute pancreatitis.

PMID- 19592691
TI  - Liver lesion associated with gynaecological pathology.

PMID- 19592694
TI  - A gastrointestinal cause for heart failure.

PMID- 19592695
TI  - Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological
      and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease.
AB  - Traditionally, Crohn's disease has been associated with a Th1 cytokine profile,
      while Th2 cytokines are modulators of ulcerative colitis. This concept has been
      challenged by the description of tolerising regulatory T cells (Treg) and by
      proinflammatory Th17 cells, a novel T cell population characterised by the master
      transcription factor RORgammat, the surface markers IL23R and CCR6, and by
      production of the proinflammatory cytokines IL17A, IL17F, IL21, IL22 and IL26,
      and the chemokine CCL20. Th17 cells differentiate under the influence of IL1beta,
      IL6, IL21 and IL23. Recent studies indicate that TGFbeta is essential not only
      for the development of murine Th17 cells but also for differentiation of human
      Th17 cells. TGFbeta reciprocally regulates the differentiation of inflammatory
      Th17 cells and suppressive Treg subsets, with the concomitant presence of
      proinflammatory cytokines favouring Th17 cell differentiation. Several studies
      demonstrated an important role of Th17 cells in intestinal inflammation,
      particularly in Crohn's disease. Genome-wide association studies indicate that
      IL23R and five additional genes involved in Th17 differentiation (IL12B, JAK2,
      STAT3, CCR6 and TNFSF15) are associated with susceptibility to Crohn's disease
      and partly also to ulcerative colitis. Taken together, both Th1 and Th17 cells
      are important mediators of inflammation in Crohn's disease, although activities
      previously ascribed to IL12 may be mediated by IL23. Anti-IL12/IL23p40 antibody
      therapy, which targets both Th1 and Th17 cells, is effective in Crohn's disease.
      However, the complex relationship between Th1 and Th17 cells has not been
      completely analysed. This will be of great importance to delineate the specific
      contributions of these cells to Crohn's disease and other autoimmune diseases.

PMID- 19592696
TI  - NOTES for colorectal neoplasia--surgery through the looking glass.

PMID- 19592697
TI  - Adiponectin and signal pathways in obesity-induced colon cancer.

PMID- 19592699
TI  - A clinical case of delayed caecal perforation.

PMID- 19592700
TI  - Elastography for the non-invasive assessment of liver disease: limitations and
      future developments.

PMID- 19592702
TI  - Comments on hereditary pancreatitis.

PMID- 19592703
TI  - Structure and function of the two tandem WW domains of the pre-mRNA splicing
      factor FBP21 (formin-binding protein 21).
AB  - Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and
      two tandem WW domains. It is a component of the spliceosomes and interacts with
      several established splicing factors. Here we demonstrate for the first time that
      FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing
      activation function and interaction with the splicing factor SIPP1 (splicing
      factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW
      domains of group III. We determined the solution structure of the tandem WW
      domains of FBP21 and found that the WW domains recognize peptide ligands
      containing either group II (PPLP) or group III (PPR) motifs. The binding
      interfaces involve both the XP and XP2 grooves of the two WW domains.
      Significantly, the tandem WW domains of FBP21 are connected by a highly flexible
      region, enabling their simultaneous interaction with two proline-rich motifs of
      SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the
      conjugation of two low affinity interactions with the tandem WW domains. Our
      study provides a structural basis for understanding the molecular mechanism
      underlying the functional implication of FBP21 and the biological specificity of
      tandem WW domains.

PMID- 19592704
TI  - Targeting of neutral cholesterol ester hydrolase to the endoplasmic reticulum via
      its N-terminal sequence.
AB  - Neutral cholesterol ester hydrolase (NCEH) accounts for a large part of the nCEH
      activity in macrophage foam cells, a hallmark of atherosclerosis, but its
      subcellular localization and structure-function relationship are unknown. Here,
      we determined subcellular localization, glycosylation, and nCEH activity of a
      series of NCEH mutants expressed in macrophages. NCEH is a single-membrane
      spanning type II membrane protein comprising three domains: N-terminal,
      catalytic, and lipid-binding domains. The N-terminal domain serves as a type II
      signal anchor sequence to recruit NCEH to the endoplasmic reticulum (ER) with its
      catalytic domain within the lumen. All of the putative N-linked glycosylation
      sites (Asn(270), Asn(367), and Asn(389)) of NCEH are glycosylated. Glycosylation
      at Asn(270), which is located closest to the catalytic serine motif, is important
      for the enzymatic activity. Cholesterol loading by incubation with acetyl-LDL
      does not change the ER localization of NCEH. In conclusion, NCEH is targeted to
      the ER of macrophages, where it hydrolyzes CE to deliver cholesterol for efflux
      out of the cells.

PMID- 19592705
TI  - Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters
      of postprandial lipid metabolism in healthy young men.
AB  - The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids,
      but the majority of lipid metabolism takes place in the postprandial state and
      knowledge about gene regulation in this state is scarce. With the aim of
      characterizing possible regulators of lipid metabolism, we studied the effects of
      nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism.
      Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 
      2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886
      (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and
      A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg
      of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples
      were extracted for 11 h after the meal. Total cholesterol and fractions [HDL
      cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich
      lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and
      apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele
      and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers
      of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma
      concentration during this state. APOC3 -640 was associated with altered TG
      kinetics but not its magnitude. We have identified new associations between SNPs
      in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.

PMID- 19592707
TI  - New strategies for novel antibiotics: peptides targeting bacterial cell
      membranes.
AB  - Membranes are targets of host defence or antimicrobial peptides, effector
      molecules of innate immunity that evolved in nature to contend with invaders as
      an active system of defence. The different physicochemical properties of the
      lipids found in biological membranes allow antimicrobial peptides to discriminate
      between bacterial and mammalian cell membranes. Such cationic amphipathic
      peptides will interact predominantly with negatively charged lipids exposed on
      the outer leaflet of bacterial cell membranes. The molecular mechanism(s) of
      membrane rupture mutually depends on the nature of the peptide and membrane lipid
      composition. Biophysical studies demonstrated a complex behavior in terms of
      membrane perturbation, which can range from pore formation to micellization
      (carpet model). Peptides aligned parallel to the membrane surface can induce a
      quasi-interdigitated structure in the gel phase, while depending on the
      hydrophobic matching of the lipid bilayer core and the peptide membrane thinning
      or thickening can be observed in the fluid phase. As a consequence, besides of
      peptide-lipid pores, formation of peptide-enriched membrane domains and promotion
      of cubic structures can be observed, which adversely affect membrane integrity
      and function. A strategy using the membrane damaging properties of these peptides
      will form the basis for the development of such peptides as potential novel
      antibiotic drugs.

PMID- 19592706
TI  - Older adult's acceptability ratings of treatments for verbal agitation in persons
      with dementia.
AB  - BACKGROUND/RATIONALE: Various interventions are available to manage verbal
      agitation (VA), but our understanding regarding their acceptability is limited.
      The purpose of this study is to compare the acceptability of 3 interventions from
      the point of view of elderly individuals: direct interaction (DI), differential
      reinforcement of incompatible behaviors (DRI), and risperidone (RIS). METHODS:
      Participants (N = 69) evaluated the acceptability of each treatment according to
      the description of a fictional person who demonstrated aggressive or
      nonaggressive VA. RESULTS: There is an interaction between the type of
      intervention and the severity of VA. For nonaggressive VA, DI is the most
      acceptable intervention followed by DRI and RIS. For aggressive VA, DI and DRI
      are more acceptable than RIS, but there is not a significant difference between
      them. The acceptability of each intervention is not associated with the
      participants' characteristics. CONCLUSION: The results of this study highlight
      the acceptability of DI for managing VA.

PMID- 19592708
TI  - What determines the thickness of a biological membrane.
AB  - Membrane thickness is thought to play a key role in protein function. Thus
      understanding the cell's ability to modulate the thickness of its membranes is
      essential in elucidating the structure/function relationship in biological
      membranes. We have investigated the influence of cholesterol on the structure of
      "thin" (diC14:1PC) and "thick" (diC22:1PC) phospholipid bilayers using oriented
      multibilayers and small angle neutron diffraction. Neutron contrast variation was
      used to determine the structure factors and the distribution of water across the
      bilayers. We found that in response to cholesterol, bilayer thickness changed in
      a similar fashion in both systems. The thickening of bilayers was rationalized in
      terms of cholesterol's ordering effect on the lipid's acyl chains, which
      dominates over the other option of rectifying the hydrophobic mismatch,
      surprisingly even in the case of diC22:1PC and cholesterol.

PMID- 19592711
TI  - Interaction of short-fragmented DNA with dipalmitoylphosphatidylcholine bilayers
      in presence of zinc.
AB  - The structure and temperature behaviour of the DNA+dipalmitoylphosphatidylcholine
      (DPPC) bilayer as a function of ZnCl2 concentration were examined using
      differential scanning calorimetry (DSC), small-angle neutron scattering (SANS)
      and small-angle X-ray diffraction (SAXD). Experiments revealed the coexistence of
      two lamellar phases in the mixture: the L(PC) phase, formed due to Zn(2+) binding
      to the DPPC bilayers, and the condensed lamellar phase L(DNA+PC) with DNA strands
      packed between the DPPC bilayers. With increasing concentration of zinc, the
      temperature of the gel - liquid-crystal phase transition of DPPC increases in
      both phases, and the volume fraction of L(DNA+PC) phase decreases. In the gel
      state (at 20 degrees C), the repeat distance of L(DNA+PC) phase is constant,
      d(DNA+PC) approximately 8.3 nm, up to 20 mmol/l of ZnCl2, and increases for
      higher concentrations of the salt. The periodicity of the L(PC) lamellar phase
      decreases substantially with the increasing concentration of the salt in the
      mixture. In the liquid-crystalline state, concentrations above 20 mmol/l ZnCl2
      promote the dissolution of the L(DNA+PC) phase into DPPC + Zn(2+) unilamellar
      vesicles and DNA is neutralized by Zn(2+) ions. The screening of Zn(2+) charge
      and the formation of a diffuse double layer due to increasing ionic strength of
      solution are responsible for the observed changes.

PMID- 19592712
TI  - Hydrodynamic size of DNA/cationic gemini surfactant complex as a function of
      surfactant structure.
AB  - The present study deals with the determination of hydrodynamic size of
      DNA/cationic gemini surfactant complex in sodium bromide solution using the
      dynamic light scattering method. Cationic gemini surfactants with polymethylene
      spacer of variable length were used for the interaction with DNA. The scattering
      experiments were performed at constant DNA and sodium bromide concentrations and
      variable surfactant concentration in the premicellar and micellar regions as a
      function of surfactant spacer length. It was found that the DNA conformation
      strongly depends on the polymethylene spacer length as well as on the surfactant
      concentration relative to the surfactant critical micelle concentration. Gemini
      surfactant molecules with 4 methylene groups in the spacer were found to be the
      least efficient DNA compacting agent in the region above the surfactant cmc.
      Gemini molecules with the shortest spacer length (2 methylene groups) and the
      longest spacer length (8 methylene groups) investigated showed the most efficient
      DNA compaction ability.

PMID- 19592709
TI  - Effects of cholesterol and unsaturated DOPC lipid on chain packing of saturated
      gel-phase DPPC bilayers.
AB  - Wide angle x-ray scattering (WAXS) from oriented lipid multilayers was used to
      study the effect of adding cholesterol (Chol) or 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC) to gel-phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) bilayers. Small quantities (X < 0.10 mole fraction) of both molecules
      disrupt the tight packing of tilted chains of pure gel-phase DPPC, forming a more
      disordered, untilted phase. The addition of larger quantities of DOPC causes the
      sample to phase-separate into a gel-phase, characterized by a narrow WAXS peak,
      and liquid disordered phase, characterized by wide, diffuse WAXS scattering. In
      contrast, two WAXS peaks indicative of two coexisting phases were not observed in
      Chol/DPPC mixtures (X(Chol) = 0.07 to 0.40). Instead, Chol caused a gradual
      increase in the width of the WAXS peak, consistent with a gradual change from a
      more gel-like to a more liquid-like state rather than passing through a region of
      two phase coexistence. Our WAXS data include a huge amount of information. A new
      method of analysis suggests that WAXS data may provide definitive results
      relating to the disagreements between previously published phase diagrams for
      Chol/DPPC.

PMID- 19592710
TI  - A layer model of ethanol partitioning into lipid membranes.
AB  - The effect of membrane composition on ethanol partitioning into lipid bilayers
      was assessed by headspace gas chromatography. A series of model membranes with
      different compositions have been investigated. Membranes were exposed to a
      physiological ethanol concentration of 20 mmol/l. The concentration of membranes
      was 20 wt% which roughly corresponds to values found in tissue. Partitioning
      depended on the chemical nature of polar groups at the lipid/water interface.
      Compared to phosphatidylcholine, lipids with headgroups containing
      phosphatidylglycerol, phosphatidylserine, and sphingomyelin showed enhanced
      partitioning while headgroups containing phosphatidylethanolamine resulted in a
      lower partition coefficient. The molar partition coefficient was independent of a
      membrane's hydrophobic volume. This observation is in agreement with our
      previously published NMR results which showed that ethanol resides almost
      exclusively within the membrane/water interface. At an ethanol concentration of
      20 mmol/l in water, ethanol concentrations at the lipid/water interface are in
      the range from 30-15 mmol/l, corresponding to one ethanol molecule per 100-200
      lipids.

PMID- 19592713
TI  - Dynamics of hydration water in proteins.
AB  - Thermodynamic and transport properties of liquid water are determined essentially
      by inter-molecular hydrogen bonds and their dynamics. Because the molecular
      dynamics depends mostly on geometric constrains and dynamics of hydrogen bonds,
      it is shown that a simple statistics on the number of bonds, including at the
      vicinity of hydrophilic substrates describes well the temperature dependence of
      water diffusion on the surface of a small peptide. Experiments were performed by
      incoherent quasi-elastic neutron scattering giving information about the hydrogen
      bond lifetime and the residence time of the water molecules. In order to study
      the interactions between water molecules and a small hydrophobic peptide (an
      assembly of five monomers of alanine), the hydration level is changed step by
      step. The only motion of the first single water molecule of the structure is due
      to hydrogen libration. The first two added water molecules bind with the
      hydrophilic site of the peptide and have only the dynamics of the bond breaking.
      The other hydration molecules show fast diffusive motions on the surface of the
      peptide.

PMID- 19592715
TI  - H(2)S and HS(-) donor NaHS inhibits intracellular chloride channels.
AB  - We have characterized the effect of H(2)S on single channel properties of the
      chloride channels derived from the rat heart lysosomal vesicles incorporated into
      a bilayer lipid membrane. The single chloride channel currents were measured in
      250 : 50 mmol/l KCl cis/trans solutions. H(2)S inhibited the chloride channels by
      decreasing the channel open probability in a concentration-dependent manner. The
      inhibitory effect of H(2)S was side-dependent with the IC(50) values of 42 and 75
      micromol/l for the trans and the cis sides, respectively. The mixture of H2S with
      the NO donor S-nitroso-N-acetyl-DL-penicillamine had smaller effect (IC(50) = 180
      micromol/l) than H(2)S alone. We assume that the inhibitory effect of H(2)S on
      chloride channels may be responsible for some of its numerous biological effects.

PMID- 19592714
TI  - Structure and flexibility within proteins as identified through small angle X-ray
      scattering.
AB  - Flexibility between domains of proteins is often critical for function. These
      motions and proteins with large scale flexibility in general are often not
      readily amenable to conventional structural analysis such as X-ray
      crystallography, nuclear magnetic resonance spectroscopy (NMR) or electron
      microscopy. A common evolution of a crystallography project, once a high
      resolution structure has been determined, is to postulate possible sights of
      flexibility. Here we describe an analysis tool using relatively inexpensive small
      angle X-ray scattering (SAXS) measurements to identify flexibility and validate a
      constructed minimal ensemble of models, which represent highly populated
      conformations in solution. The resolution of these results is sufficient to
      address the questions being asked: what kinds of conformations do the domains
      sample in solution? In our rigid body modeling strategy BILBOMD, molecular
      dynamics (MD) simulations are used to explore conformational space. A common
      strategy is to perform the MD simulation on the domains connections at very high
      temperature, where the additional kinetic energy prevents the molecule from
      becoming trapped in a local minimum. The MD simulations provide an ensemble of
      molecular models from which a SAXS curve is calculated and compared to the
      experimental curve. A genetic algorithm is used to identify the minimal ensemble
      (minimal ensemble search, MES) required to best fit the experimental data. We
      demonstrate the use of MES in several model and in four experimental examples.

PMID- 19592716
TI  - Oxidative injury induced by hypochlorous acid to Ca-ATPase from sarcoplasmic
      reticulum of skeletal muscle and protective effect of trolox.
AB  - Hypochlorous acid (HOCl) concentration-dependently decreased ATPase activity and
      SH groups of pure Ca-ATPase from sarcoplasmic reticulum (SERCA) of rabbit
      skeletal muscle with IC(50) of 150 micromol/l and 6.6 micromol/l, respectively.
      This indicates that SH groups were not critical for impairment of Ca-ATPase
      activity. Pure Ca-ATPase activity was analysed individually with respect to both
      substrates, Ca(2+) and ATP. Concerning dependence of ATPase activity on HOCl (150
      micromol/l) as a function of free Ca(2+) and ATP, V(max) of both dependences
      decreased significantly, while the affinities to individual substrates were not
      influenced, with the exception of the regulatory binding site of ATP. On
      increasing HOCl concentration, fluorescence of fluorescein-5-isothiocyanate
      (FITC) decreased, indicating binding of HOCl to nucleotide binding site of SERCA.
      A new fragment appeared at 75 kDa after HOCl oxidation of SR, indicating
      fragmentation of SERCA. Fragmentation may be associated with protein carbonyl
      formation. The density of protein carbonyl bands at 75 and 110 kDa increased
      concentration- and time-dependently. Trolox (250 micromol/l) recovered the Ca
      ATPase activity decrease induced by HOCl, probably by changing conformational
      properties of the Ca-ATPase protein. Trolox inhibited FITC binding to SERCA.

PMID- 19592718
TI  - Interreality: A New Paradigm for E-health.
AB  - "Interreality" is a personalized immersive e-therapy whose main novelty is a
      hybrid, closed-loop empowering experience bridging physical and virtual worlds.
      The main feature of interreality is a twofold link between the virtual and the
      real world: (a) behavior in the physical world influences the experience in the
      virtual one; (b) behavior in the virtual world influences the experience in the
      real one. This is achieved through: (1) 3D Shared Virtual Worlds: role-playing
      experiences in which one or more users interact with one another within a 3D
      world; (2) Bio and Activity Sensors (From the Real to the Virtual World): They
      are used to track the emotional/health/activity status of the user and to
      influence his/her experience in the virtual world (aspect, activity and access);
      (3) Mobile Internet Appliances (From the Virtual to the Real One): In
      interreality, the social and individual user activity in the virtual world has a
      direct link with the users' life through a mobile phone/digital assistant. The
      different technologies that are involved in the interreality vision and its
      clinical rationale are addressed and discussed.

PMID- 19592717
TI  - Antioxidative effect of some hydroxy substituted aromatic bisimines.
AB  - This work deals with antioxidative properties of some derivatives 4,4'
      bis(dihydroxybenzylanilidenamino) diphenylmethanes and diphenylethers, which
      structure is similar to resveratrol. Four derivatives of above-mentioned
      compounds were synthesized with hydroxyl (OH) groups in various positions. It was
      found that derivatives with two OH groups in 2 and 5 positions were very good
      scavengers of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals in both methanol and
      chloroform. On the other hand derivatives with OH groups in positions 2 and 4 did
      not scavenge DPPH radicals. The calculation of free enthalpies (by quantum
      chemical method AM1) necessary for the formations of anions or radicals support
      above mentioned findings because the enthalpies for effective derivatives were
      lesser, than for ineffective ones. Also, it was found that studied compounds did
      not scavenge hydroxyl radicals whereas resveratrol did it.

PMID- 19592719
TI  - Eating disorders on the web: risks and resources.
AB  - Our work is aimed at exploring the recent literature data on web sites, forums,
      and blogs, which promote eating disorders as normal life styles and their
      implication in the changes of the psychopatology of such disorders. We also want
      to understand whether new technologies have an impact in the course of the
      disorders or, on the other hand, whether they can also represent an instrument
      for searching help or information about them. The search strategy included a
      search of PsycINFO, Medline, and Ovid databases to identify research reports
      about pro-ana sites and their implication on the course of anorexia using the
      following key words: pro-ana, thinspiration, anorexia-web, online help eating
      disorders, anorexia nation.

PMID- 19592720
TI  - 'I' and 'other' in online interactions: intersubjectivity as a social bridge.
AB  - The aim of this work is to propose Intersubjectivity as a key concept in a social
      interpretation of online dynamics while studying CyberPsychology and its
      applications. Dialogue is the inner soul of the Self, considered as "a dynamic
      multiplicity of voiced positions." The link between the Self and the Others must
      be considered too. Through dialogue, interlocutors negotiate both ideas and their
      self-images. Starting from 'single' intentions (a representation of what each
      participant wants to present outside), interactions support a co-construction of
      shared and linked images of interlocutors, called Subjectivities. These two or
      more Subjectivities are the basis of the Intersubjective dimension of an
      interaction.

PMID- 19592721
TI  - An ontology for Cognitive Behavioral Therapy. Application to Obesity.
AB  - In the last few years the use of medical and biomedical ontologies has increased
      considerably. It is very common to find applications and semantic webs using this
      kind of ontologies and a large number of papers have been written explaining why
      ontologies are useful in these fields. In this paper the use of ontologies for
      psychology and its benefits is discussed and a first ontology for obesity
      treatment is presented.

PMID- 19592722
TI  - Second life, bio-sensors, and exposure therapy for anxiety disorders.
AB  - We give an overview of the Second Life (SL) virtual world, explaining what
      objects can be manipulated to implement user-defined scenari in SL, and give an
      example of a work-in-progress scenario of exposure therapy for anxiety disorders,
      coupled with automatic processing of bio-sensed emotional signals. Both e-Health
      and emotion recognition researchers can benefit from such experiments.

PMID- 19592723
TI  - Features for culturally appropriate avatars for behavior-change promotion in at
      risk populations.
AB  - We explore how avatars can be used as social orthotics defined as therapeutic
      computer-based social companions aimed at promoting healthy behaviors. We review
      some of the health interventions deployed in helping at-risk populations along
      with some of the unique advantages that computer-based interventions can add to
      face-to-face interventions. We posit that artificial intelligence has rendered
      possible the creation of culturally appropriate dialog-agents for interventions
      and we identify specific features for social avatars that are important - if not
      necessary - when applied to the domain of social orthotic systems for health
      promotion.

PMID- 19592724
TI  - Cyberspace psychopathology.
AB  - The authors, after a initial description of the "Internet phenomenon" and more
      specifically concerning the psychological and psychopathological risks related to
      its use, propose a series of unpublished papers on this theme, developed during
      the last year.

PMID- 19592725
TI  - Social network and addiction.
AB  - In recent decades, the rapid development of innovative Internet-based
      communication technologies created a new field of academic study among scholars.
      Particularly, the attention of researchers is focusing on new ways to form
      relationship-thought social web. Social Network sites constitute a new form of
      web communities, where people meet and share interests and activities. Due to
      exponential growth of these sites, an increasing number of scholars are beginning
      to study the emergent phenomena in order to identify any psychopathological risk
      related to use of social web, such as addiction. This article examines the recent
      literature about this issue.

PMID- 19592726
TI  - Designing affective video games to support the social-emotional development of
      teenagers with autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are a group of developmental neuropsychiatric
      disorders, comprised of three diagnostic entities - autistic disorder (AD),
      Asperger's disorder (AS), and Pervasive Developmental Disorder Not Otherwise
      Specified (including atypical autism) (PDD-NOS). A number of intervention
      techniques are currently used to reduce some of the associated challenges, with
      techniques ranging from behavioral therapy to dietary interventions and
      traditional counseling. This positional paper proposes the use of video games
      which leverage affective computing technologies as intervention in autism
      spectrum disorders in the context of the use of traditional play therapy with
      adolescents, who may feel uncomfortable engaging in traditional play with toys
      they may be too old for. It aims to explore the potential for greater 'social
      physics' made possible by affective computing technologies. This involves
      computationally 'recognizing' emotions in a user, often through the use of
      multimodal affective sensors, including facial expressions, postural shifts, and
      physiological signals such as heart rate, skin conductivity, and EEG signals.
      However, it is suggested that this should be augmented by researching the effect
      of social game design mechanisms on social-emotional development, particularly
      for those who experience difficulty with social interaction.

PMID- 19592727
TI  - Scientific evidence for the effectiveness of virtual reality for pain reduction
      in adults with acute or chronic pain.
AB  - The objective of this systematic review was to determine the level of scientific
      evidence for the effectiveness of VR for pain management in adults with pain. A
      comprehensive systematic search involving major health care databases was
      undertaken to identify randomized clinical trials (RCTs) and descriptive studies.
      Twenty-seven studies were identified that fulfilled the inclusion criteria. There
      was strong (Level 1a) evidence of a greater benefit from immersive VR and limited
      evidence (Level 2a) for the effectiveness of non-immersive VR in reducing acute
      pain. Moreover, there is limited evidence (Level 2a) of effectiveness of
      immersive VR compared to no VR for reducing chronic pain. There is currently no
      published study that has explored the effectiveness of non-immersive VR for
      chronic pain (level 5). It is concluded that VR can be recommended as a standard
      or adjunct clinical intervention for pain management at least in the management
      of acute pain.

PMID- 19592728
TI  - Affective robot for elderly assistance.
AB  - Recently, several robotic solutions for the elderly have been proposed. However,
      to date, the diffusion of these devices has been limited: available robots are
      too cumbersome, awkward, and expensive to become widely adopted. Another key
      issue which reduces the appeal of assistive robots is the lack of socio-emotional
      interaction: affective interchanges represent key requirements to create
      sustainable relationships between elderly and robots. In this paper, we propose a
      new approach to enhance the acceptability of robotic systems, based on the
      introduction of affective dimensions in human-robot interaction. This strategy is
      aimed at designing a new generation of relational and cognitive robots fusing
      information from embodied unobtrusive sensory interfaces. The final objective is
      to develop embodied interfaces, which are able to learn and adapt their affective
      responses to the user's behavior. User and robot will engage in natural
      interactions, involving verbal and non-verbal communication, improving empathic
      exchange of moods and feelings. Relevant independent living and quality of life
      related issues will be addressed: on-going monitoring of health parameters,
      assistance in everyday's activities, social support and cognitive/physical
      exercises. We expect that the proposed strategy will enhance the user's
      acceptance and adoption of the assistive robotic system.

PMID- 19592729
TI  - Stress inoculation training supported by physiology-driven adaptive virtual
      reality stimulation.
AB  - Significant proportion of psychological problems related to combat stress in
      recent large peacekeeping operations underscores importance of effective methods
      for strengthening the stress resistance of military personnel. Adaptive control
      of virtual reality (VR) stimulation, based on estimation of the subject's
      emotional state from physiological signals, may enhance existing stress
      inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor
      the progress of stressful stimuli delivery to the physiological characteristics
      of each individual, which is indicated for improvement in stress resistance.
      Therefore, following an overview of SIT and its applications in the military
      setting, generic concept of physiology-driven adaptive VR stimulation is
      presented in the paper. Toward the end of the paper, closed-loop adaptive control
      strategy applicable to SIT is outlined.

PMID- 19592730
TI  - NeuroVR 1.5 in Practice: Actual Clinical Applications of the Open Source VR
      System.
AB  - At CT 2007, we presented NeuroVR (http://www.neurovr.org), a free virtual reality
      platform based on open-source software. The software allows non-expert users to
      adapt the content of 14 pre-designed virtual environments to the specific needs
      of the clinical or experimental setting. Following the feedbacks of the 700 users
      who downloaded the first version, we developed a new version - NeuroVR 1.5 - that
      improves the possibility for the therapist to enhance the patient's feeling of
      familiarity and intimacy with the virtual scene, by using external sounds, photos
      or videos. The key characteristics that make NeuroVR suitable for most clinical
      applications are the high level of control of the interaction with the tool, and
      the enriched experience provided to the patient. Actually, NeuroVR is used in the
      assessment and treatment of Obesity, Alcohol Abuse, Anxiety Disorders,
      Generalized Anxiety Disorders, and Cognitive Rehabilitation.

PMID- 19592731
TI  - The SNaP Framework: A VR Tool for Assessing Spatial Navigation.
AB  - Recent work in psychology has leveraged the power of Virtual Reality (VR) to
      study the deterioration of navigation abilities in the elderly. Much of this
      research has focused on determining the behavioral measurements and paradigms
      appropriate for such diagnoses. We present a system, the Spatial Navigation
      Paradigm (SNaP) framework, which can be used to implement a battery of spatial
      navigation paradigms. This framework integrates a popular VR environment
      development platform with an extensible representation medium to allow for the
      precise control of paradigms, the switching between input and output devices, and
      the recording of accurate behavioral measurements. A preliminary study of the
      framework indicates that novice and expert VR users are able to quickly and
      easily specify and deploy experiments and that expert VR users can easily modify
      and extend existing paradigm implementations.

PMID- 19592732
TI  - Mobile immersive virtual technologies for professional communities of practice.
AB  - This paper presents the development of an Immersive Virtual Technology (IVT)
      system serving a community of practice consisting of psychotherapists who use
      virtual environments for therapy and treatment of anxiety disorders. The
      psychosocial theoretical background includes the ethnomethodological approach,
      Situated Action Theory and the Intersubjectivity of the Utterance model. The
      dialogical importance promoted at each level of the analysis phases becomes the
      key to a deeper and more fluid understanding of the assumptions and meaning that
      guide the actions of and interactions between therapists and patients. The entire
      system design process is inspired by a dialogical perspective, which aims to
      effectively and non-rigidly integrate the design stages, analysis in context of
      use, ergonomic evaluation, creation of the virtual reality (VR) system, and final
      work on the clinical protocol in use.

PMID- 19592733
TI  - Interpersonal relationships, coping strategies and problematic internet use in
      adolescence: an italian study.
AB  - In a few years the Internet has become one of the most relevant means of
      socialization and entertainment for Italian adolescents. Studies have established
      a correlation between poor interpersonal relationship, poor cognitive coping
      strategies and Problematic Internet Use. The aim of the research was to study the
      characteristics and correlates of Problematic Internet Use in an Italian sample
      of adolescents. 98 Italian adolescents aged 14-19 were administered checklists
      assessing Problematic Internet Use, quality of interpersonal relationships, and
      cognitive-driven coping strategies. Of the participants, 36.7% are characterized
      by Problematic Internet Use. This subsample showed poorer interpersonal
      relationships and cognitive coping strategies compared to the non-problematic
      subsample. Overall quality of interpersonal relationships and cognitive coping
      strategies were found to be predictors of the level of Internet Problematic Use.

PMID- 19592734
TI  - Walking in an immersive virtual reality.
AB  - The aim of this study was to investigate the effects on gait induced by a
      completely immersive Virtual Reality (VR) with and without perturbation. Ten
      healthy subjects were analyzed during over-ground walking in different
      conditions: standard gait, VR gait and perturbed VR gait. Results showed that
      subjects immersed in the virtual environment walked slowly, with decreased
      cadence (-13%) and stride length (-28%) as well as increased base of support in
      terms of step width (+20%). The perturbation of the VR caused an interesting
      effect: many computed parameters, still away from the standard gait condition,
      improved if compared to the unperturbed VR condition. In conclusion, walking in
      VR leads to gait instability, which is less pronounced in presence of
      perturbation, probably due to the reweight of sensory inputs. This study could
      represent the first step for the application of the proposed VR environment to
      pathological subjects.

PMID- 19592735
TI  - Designing a serious game for young users: the case of happy farm.
AB  - The interactivity and attractiveness of video games are increasingly deployed for
      educational and training purposes in what are called "serious games." This paper
      describes Happy Farm, a serious game targeting young people and aimed at
      increasing their awareness of the risks connected to the consumption of
      psychoactive substances. The development of the game is driven by the premise
      that credibility and usability are pre-conditions for persuasion. The achievement
      of these qualities is pursued in the design and is generally testified by the
      results of the users' evaluation. Suggestions for the improvement of the game are
      also outlined.

PMID- 19592736
TI  - High Resolution 3D Models for the Teaching of American Sign Language.
AB  - Millions of Americans in all age groups are affected by deafness and impaired
      hearing. They communicate with others using the American Sign Language (ASL).
      Teaching is tutorial (person-to-person) or with limited video content. We believe
      that high resolution 3D models and their animations can be used to effectively
      teach the ASL, with the following advantages over the traditional teaching
      approach: a) signing can be played at varying speeds and as many times as
      necessary, b) being 3-D constructs, models can be viewed from diverse angles, c)
      signing can be applied to different characters (male, female, child, elderly,
      etc.), d) special editing like close-ups, picture-in-picture, and phantom
      movements, can make learning easier, and e) clothing, surrounding environment and
      lighting conditions can be varied to present the student to less than ideal
      situations.

PMID- 19592737
TI  - Addiction to internet replies.
AB  - This research introduces a new addictive behavior in cyberspace, which is called
      Internet Reply Addiction. This phenomenon was found and empirically investigated
      in Korea where addictive behavior on Internet reply is common. This research
      suggests that the cause of this kind of addiction can be inferred from the
      Confucian cultural tradition that oppresses free expressions of individuals in
      real life settings.

PMID- 19592738
TI  - Tools, perspectives and avatars in blended reality space.
AB  - Blended Reality Space is our term for an interactive mixed-reality environment
      where the physical and the virtual are intimately combined in the service of
      interaction goals and communication environments aimed at health support and
      rehabilitation. The present study examines the effect on rated presence and self
      presence of three key factors in the way blended realities may be implemented for
      these purposes. Our findings emphasize the importance of tangibility for
      presence, but suggest that presence and self-presence are unrelated phenomena.
      These findings will be incorporated into design principles for our planned work
      to develop free movement-based interactions for motor rehabilitation as well as
      blended-reality spaces for collaboration between hospitals, care organizations,
      and the home.

PMID- 19592739
TI  - Facial Synthesys of 3D Avatars for Therapeutic Applications.
AB  - People with autism spectrum disorder (ASD) find it difficult to recognize and
      respond to emotions conveyed by the face. Most existing methodologies to teach
      people with ASD to recognize expressions use still images, and do not take into
      account that facial expressions have movement. We propose a new approach that
      uses state of the art technology to solve the problem and to improve
      interactivity. It is based on an avatar-user interaction model with real time
      response, which builds upon the patient-therapist relationship: it is designed to
      be used by the therapist and the patient. The core technology behind it is based
      on a technique we have developed for real time facial synthesis of 3D characters.

PMID- 19592740
TI  - A Free Tool for Motor Rehabilitation: NeuroVR 1.5 with CamSpace.
AB  - NeuroVR 1.5 is a cost-free virtual reality platform based on open-source
      components, allowing professionals to easily modify a virtual world, to best suit
      the needs of the clinical setting. The goal of the present project is to extend
      the functionalities of this platform by allowing users to interact with the
      virtual environment by using gestures detected by a webcam. To this end, we used
      CamSpace Beta 7, a cost-free and user-friendly computer vision technology. We
      describe how this integrated approach can be used to implement cognitive and
      motor training programs, involving partial or full-body movements.

PMID- 19592741
TI  - Virtual reality interventions for rehabilitation: considerations for developing
      protocols.
AB  - This paper is a preliminary report on a work in progress that explores the
      existence of practice effects in early use of virtual reality environments for
      rehabilitation purposes and the effects of increases in level of difficulty as
      defined by rate of on-screen objects.

PMID- 19592742
TI  - Virtual reality rehabilitation of spatial abilities after brain damage.
AB  - Current rehabilitation of navigation and spatial orientation ability after brain
      damage is generally focused on training within the rehabilitation hospital or the
      patient's home as part of common physio- and occupational therapy sessions. To
      further promote generalization of gained abilities and to quantify functional
      improvements, this project aims at developing a Virtual Reality (VR) application
      that can be used for training and assessment of spatial orientation and
      navigation skills in brain-damaged patients. The training is administered after
      the standard hospital rehabilitation training is completed. Additionally, the
      program will be used as an assessment tool to quantify the participants'
      wayfinding performance. The data will be compared with real-world navigation
      performance in tasks of similar complexity to evaluate real-world transfer of the
      VR training. Currently, the application is under development and basic
      functionality and data acquisition are being implemented.

PMID- 19592743
TI  - Cybertherapy meets facebook, blogger, and second life: an italian experience.
AB  - Our project is based on the study of Cybertherapy in the international sphere
      (USA, Northern Europe) and on the application of this discipline to the Italian
      psychiatric and psychological reality. CyberTherapy can be used as an "aim",
      referring to it as real and proper therapy, which lives on personalized paths
      created by a qualified staff, conceived as ludic, for recreational, psycoterapic,
      and educational purpose. Moreover, Cybertherapy can be used as a "mean" (and in
      this way we want to propose it) with the aim of making the user, who feels a
      psychiatric or a psychological uneasiness, to become closer to qualified staff; a
      considerable advantage of this discipline is to reduce to a minimum the initial
      embarrassment which is created between the specialist and the psychiatric
      patient, uneasiness stirred up and accentuated by the problem, which is
      unfortunately not resolved in the Italian sphere of the Stigma.

PMID- 19592744
TI  - Self presentation in blogs and social networks.
AB  - Recent approaches to the study of identity in online contexts underline how
      people on the Internet have multiple identities and are at risk of identity
      fragmentation. Subjectivities are context-specific, negotiated with other people
      and actualized in Self Presentations. The aim of this study is to investigate how
      social media users deal with choices regarding their Self Presentation and how
      different profiles of the same person relate to one other. Thirty-six users with
      accounts on two blog-hosting services and one social network website answered an
      online structured interview and elaborated on the different choices of Self
      Presentation for each service. Content Results show users accurately and
      consciously choose the way they present their Self according to their aims,
      actual and potential readership, and the technical possibilities of the media.
      Answers also show that people online are conscious of the multiple presentations
      they enact, and they feel an underlining sense of unity and coherence, which may
      be traced back to the concept of Self.

PMID- 19592745
TI  - Next generation stress inoculation training for life saving skills using
      prosthetics.
AB  - By integrating medical science with cutting edge simulation and training
      technologies, realistic prosthetic tissue, wounds, and part task trainers have
      been developed for the training of trauma care clinicians. The next generation of
      Stress Inoculation Training (SIT) includes the use of prosthetics developed based
      on human anatomy and physiology, material science, and nanotechnology. Testing
      has revealed that these products are highly useful and reliable.

PMID- 19592746
TI  - A Comparative Analysis between Experts and Novices Interacting with a Virtual
      Patient with PTSD.
AB  - Virtual patients will provide a means to train the next generation of clinical
      residents. Interacting and engaging with virtual characters portraying
      standardized patients can have meaningful outcomes. As a cumulative set of data
      analysis, we investigate the comparison of how well novices, subjects without any
      clinical interviewing background, with experts, clinicians, or resident student
      clinicians with interviewing skills to assess if they could elicit the proper
      information from verbal interactions with a virtual character.

PMID- 19592747
TI  - The receptiveness of stress management techniques by military personnel.
AB  - Many military service members suffer from stress. Sixty Soldiers participated in
      a study designed to test receptivity to stress management techniques. Preliminary
      analyses of surveys and a focus group suggested that participants not only liked
      practicing relaxation techniques but would also continue practicing these after
      completion of the present study.

PMID- 19592748
TI  - The use of biofeedback in clinical virtual reality: the intrepid project.
AB  - In our protocol for the treatment of Generalized Anxiety Disorders we use Virtual
      reality (VR) to facilitate emotional regulation and the relaxation process. Using
      a biofeedback biomonitoring system (GSR, HR, Thermal) the patient is made aware
      of his or her reactions through the modification of some features of the VR
      environment in real time. Using mental exercises the patient learns to control
      these physiological parameters and using the feedback provided by the virtual
      environment is able to gauge his or her success. To test this concept, we planned
      a randomized controlled trial (NCT00602212), including three groups of 15
      patients each (for a total of 45 patients): (1) the VR group, (2) the non-VR
      group, and (3) the waiting list (WL) group.

PMID- 19592749
TI  - Transcranial Doppler: a non-invasive tool for monitoring brain activity in
      virtual reality therapy.
AB  - In this work, we propose the use of Transcranial Doppler Monitoring (TCD) as a
      tool to measure brain activity during the exposure to Virtual Environments (VE)
      used in clinical therapy sessions. The technique is non-invasive, and can be
      easily integrated with Virtual Reality (VR) settings. Moreover, it provides a
      high temporal resolution, which grants the possibility to analyze changes in
      brain activity during the evolution of a clinical session and to correlate them
      with specific events that may occur in the VE. We have performed two studies
      combining TCD with VR. Results of these studies show that it is feasible to use
      this technique in combination with VR settings designed for virtual therapy. It
      was observed that immersion and navigation modifications in the VE generated
      changes in brain activity that can be detected using TCD.

PMID- 19592750
TI  - Interactive highly realistic virtual reality as a tool for understanding the
      genesis and treatment of psychotic symptoms.
AB  - Schizophrenia can be a devastating lifelong psychotic disorder with a poor
      prognosis. National guidelines in the UK recommend the provision of cognitive
      behavioral therapy (CBT) to all those suffering with psychotic disorders, but
      there is a lack of trained therapists in the UK able to provide such a treatment.
      Developing high quality automated technologies that can serve as an adjunct to
      conventional CBT should enhance the provision of this therapy, and increase the
      efficiency of the therapists in practice. The latter will occur by enabling
      alternate professionals to aid in the delivery of therapy, to enable behavioral
      experiments to be conducted in the clinic, and for sessions to be recorded and re
      played such that the patient can deliver therapy to him or herself. As such the
      system will enable patients to become experts in, and providers of, their own
      treatment and decrease the number of sessions needed to be led by a trained CBT
      therapist. A key feature of any such system is the level of realism required to
      ensure a compelling session in which the user is not adversely affected by the
      system itself. This paper presents a high-fidelity virtual environment to help
      better understand the environmental triggers for psychosis.

PMID- 19592751
TI  - A Cross-Cultural Validation of VR Treatment System for Flying Phobia in the
      Mexican Population.
AB  - Anxiety as a symptom or disorder is affected by multiple variables such as
      antecedent events, interpretation of the events, psychological vulnerability, and
      individual differences in the reaction towards an event. Nowadays, virtual
      reality therapy is used as therapeutic tool for patients suffering from some kind
      of anxiety disorder. In Mexico, the National Survey on Psychiatric Epidemiology
      [1] informed that anxiety disorders are the most common disorders followed by
      affective disorders, which are more prevalent in women than in men. Among the
      different anxiety disorders, the category of specific phobias (7.1%) was the most
      common. Based on this demand, a collaborative effort between research groups from
      the University Jaume I in Spain and the National Autonomous University of Mexico
      (UNAM), initiated a project which purpose was the technological transfer of
      systems based on virtual reality for the treatment of Fear of Flying to be
      implemented and evaluated in the Mexican population. The treatment protocol
      developed by Botella et al., [2] has been applied to five volunteer participants.
      In this paper we present data of adapted treatment protocols in Mexican
      population that support the efficacy of VR of treatment of fear of flying,
      achieved by the Spanish research group.

PMID- 19592753
TI  - Online Game Addiction among Chinese College Students Measurement and Attribution.
AB  - This study made an initial attempt to measure and attribute online game addiction
      among Chinese college students. We generated three factors of online game
      addiction: Control Disorder, Conflict, and Injury, as well as proposed a
      comprehensive model that attributed online game addiction to three groups of
      driving forces: environmental influences (most significant), characteristics of
      online games, and personal reasons.

PMID- 19592752
TI  - Telepsychiatry and cultural barriers in Korea.
AB  - This research was performed in order to empirically prove that telepsychiatry can
      result in overcoming of the Confucian cultural barrier which discouraged Korean
      patients from seeking psychiatric care. The Confucian culture of Korea forces its
      members to observe absolute conformity to the social norm. In this kind of
      culture it is very hard to admit one's mental illness and to seek medical help.
      Thus telepsychiatry might be a good alternative to face-to-face meeting-based
      psychiatry especially in culturally inhibitive places such as Korea. We conducted
      a telepsychiatry experiment using Instant Messenger with 93 volunteers who had an
      experience of seeing a psychiatrist in person. The result shows that people tend
      to think that telepsychiatry allowed them to break out of the Confucian cultural
      protocol which put heavy emphasis on avoiding any irregular thought.

PMID- 19592754
TI  - A web-based tool for cooperating behaviors in eating and physical activity
      control.
AB  - The field of information technology and the Internet for health care has
      developed rapidly in the last few years. Furthermore, new services devoted to
      improve personalized healthcare are emerging from current web-orientated
      research. Control of eating and physical activity behaviors can be performed in a
      computer mediated way as a social networking application. To this purpose, we
      designed and implemented a web application based on the cooperation between two
      communities: Patients and Nutritionists. The patients are able to cooperate as
      within a self-help group, while nutritionists can guide patients struggling with
      incorrect lifestyle and its consequences.

PMID- 19592755
TI  - A comparison of different survey periods in online surveys of persons with eating
      disorders and their relatives.
AB  - Evaluations of Internet-based interventions offered to patients with mental or
      psychosomatic illnesses are mostly carried out in the form of online surveys. Up
      until now, the methods used in carrying out these evaluations have seldom been
      systematically investigated. This study tested whether modifying this time
      interval brings about changes in the respondents' response behavior and the make
      up of the sample. Two survey strategies were compared: a post-block survey (with
      a variable time interval between the Internet-based intervention and the online
      survey) and a post-spot survey (time interval standardised to 90 days). In the
      post-spot survey it was possible to prove a higher response rate (39.9%) than in
      the post-block survey (28.0%) as well as a higher number of questionnaires
      completed correctly and in full. No differences were identified in the basic
      characteristics of the random samples. It was possible to demonstrate that the
      quality of the online survey could be improved by standardising the length of
      time. Standardisation of the time difference implies a controllable degree of
      influence on the quality of the evaluations.

PMID- 19592756
TI  - Playmancer project: a serious videogame as an additional therapy tool for eating
      and impulse control disorders.
AB  - Reviews and few non-controlled studies showed the effectiveness of several
      specific designed computer video-games as an additional form of treatment in
      several areas. However, there is a lack in the literature of specially designed
      serious-games for treating mental disorders. Playmancer (ICT European initiative)
      aims to develop and assess a serious videogame that may help to treat underlying
      processes (e.g. lack of self-control strategies) in Eating and Impulse control
      disorders. Preliminary data will be shown.

PMID- 19592757
TI  - Cybersickness and Anxiety During Simulated Motion: Implications for VRET.
AB  - Some clinicians have suggested using virtual reality environments to deliver
      psychological interventions to treat anxiety disorders. However, given a
      significant body of work on cybersickness symptoms which may arise in virtual
      environments - especially those involving simulated motion - we tested (a)
      whether being exposed to a virtual reality environment alone causes anxiety to
      increase, and (b) whether exposure to simulated motion in a virtual reality
      environment increases anxiety. Using a repeated measures design, we used Kim's
      Anxiety Scale questionnaire to compare baseline anxiety, anxiety after virtual
      environment exposure, and anxiety after simulated motion. While there was no
      significant effect on anxiety for being in a virtual environment with no
      simulated motion, the introduction of simulated motion caused anxiety to
      significantly increase, but not to a severe or extreme level. The implications of
      this work for virtual reality exposure therapy (VRET) are discussed.

PMID- 19592758
TI  - Neural responses to elements of a web-based smoking cessation program.
AB  - An increasing number of smokers are obtaining information from the web to help
      them quit smoking. In this study, we examined how smokers process different types
      of messages similar to those from a web-based smoking cessation program:
      personalization/feedback ("Jane, you are a 23-year old female smoker"),
      motivational ("If you quit smoking, you could save $1200 a year"), and
      instructional ("When you feel angry, talk to someone instead of smoking")
      messages. Using functional magnetic resonance imaging, smokers were exposed to
      the messages. On a later session, participants completed an online tailored
      smoking cessation program and started on a 10-week course of nicotine patch.
      Results show that participants indeed process the messages differently,
      activating brain regions associated with self-related processing
      (personalization/feedback), anticipated reward processing (motivational messages)
      and rules processing (instructional messages). This research is relevant for
      advancing web-based tailored interventions for substance use.

PMID- 19592759
TI  - Psychophysiological arousal and craving in smokers, deprived smokers, former
      smokers, and non-smokers.
AB  - This study investigates the biometric signature associated with tobacco craving
      and stress elicitation using principles of cue reactivity. Seventy-five non
      smokers and smokers (half of whom were tobacco-deprived for 6 hours) took part in
      a standardized laboratory session during which they were presented with a series
      of film clips designed to arouse fear, amusement, or craving. Participants self
      reported their emotional response to each film clip and wore non-invasive
      biosensors to collect physiologic data. Findings indicate different patterns of
      physiologic arousal for smokers than non-smokers; and that among smokers,
      deprived smokers had significantly different arousal patterns than non-deprived
      smokers. This article describes how the elicitation of stress and craving can
      contribute to the prediction of arousal patterns associated with tobacco craving
      and how this can create new opportunities for smoking cessation intervention. A
      comparison of each group's patterns of arousal and physiologic activity is
      presented, with particular focus on the differences between smokers and deprived
      smokers.

PMID- 19592760
TI  - Changes in EEG Behavior through Feedback Presentation.
AB  - Performance of brain-computer interface (BCI) will depend, to a great extent, on
      the ability of subjects to control their own electroencephalographic signals
      (EEG). To this end, it is necessary to follow a suitable training and to provide
      some type of visual feedback. The objective of this study is to explore the
      possibility of improving the EEG control via feedback presentation. Eighteen
      untrained subjects, divided in two groups, were trained using a BCI system based
      on virtual reality techniques, which submits subjects to a more familiar
      environment, such as controlling a car to avoid different obstacles. Different
      types of obstacles were introduced for each group. Significant differences in
      classification error rates between both groups were obtained during the last
      second of the feedback period.

PMID- 19592761
TI  - EEG, HRV and Psychological Correlates while Playing Bejeweled II: A Randomized
      Controlled Study.
AB  - Stress related medical disorders such as cardiovascular disease, diabetes,
      depression, and anxiety are serious medical issues that can cause disability and
      death. Interventions to prevent their development and exacerbation are needed.
      Casual video games (CVGs) are fun, easy to play, spontaneous and tremendously
      popular. People report that they play these games because they decrease their
      stress and improve their mood. This study tested this theory by comparing people
      playing Bejeweled II a popular CVG with control subjects measured under similar
      conditions. Electroencephalographic (EEG) changes after playing Bejeweled II were
      consistent with increased mood and corroborated with similar findings on
      psychological reports. Moreover, heart rate variability (HRV) changes consistent
      with autonomic nervous system relaxation or decreased physical stress were also
      recorded. It is concluded, therefore, that playing a CVG like Bejeweled II can
      increase mood and decrease stress. These finding have broad implications and
      include the potential development of prescriptive interventions using Bejeweled
      II to prevent and treat stress related medical disorders. Finally, these findings
      demonstrate a method using EEG, HRV and psychological correlates to understand
      the psychophysiological or cybernetic interconnection between participant and
      video game.

PMID- 19592762
TI  - Mobile serious games for collaborative problem solving.
AB  - This paper presents the results obtained from the implementation of a series of
      learning activities based on mobile serious games (MSG) for the development of
      problem-solving and collaborative skills in Chilean 8th grade students. Three
      MSGs were developed and played by teams of four students, who had to solve the
      problems posed by the game collaboratively. The data shows that the experimental
      group had a higher perception of their own skills of collaboration and of the
      plan execution dimension of problem solving than the control group, providing
      empirical evidence regarding the contribution of MSGs to the development of
      collaborative problem-solving skills.

PMID- 19592763
TI  - Treadmill Interface for Virtual Reality vs. Overground Walking: A Comparison of
      Gait in Individuals with and without Pain.
AB  - A treadmill (TR) interfaced with a virtual reality (VR) system can provide an
      engaging environment that could improve activity adherence and walking function
      for individuals with pain. Furthermore, inclusion of discrete visual and auditory
      cues into the VR environment (e.g. manipulation of optic flow speed or audio beat
      frequency) could improve walking. This study compared gait characteristics (speed
      and cadence) of a baseline over ground walk (OVR) with a TR walk as part of a
      project to develop gait referenced visual and auditory frequency cues. Thirty-six
      participants aged between 22 and 80 years, with pain (n=19) and without pain
      (n=17) took part. A 2 x 2 MANOVA conducted on the speed and cadence for all
      participants showed a significant difference between pain and control groups for
      speed (F<inf>1,34</inf>=9.56, p<0.01) and cadence (F<inf>1,34</inf>=5.75,
      p<0.05), as well as a significant decrease from overground to treadmill
      conditions for both speed (F<inf>1,34</inf>=81.39, p<0.01) and cadence
      (F<inf>1,34</inf>=25.46, p<0.01). Differences between OVR and TR walking indicate
      that visual or auditory cues for VR walk training should be referenced according
      to TR baseline measures.

PMID- 19592764
TI  - Behaviour of motor disabilities and appearance of visual hallucinations in
      patients with Parkinson's disease in a virtual environment.
AB  - We studied 23 Parkinson's disease (PD) non-demented patients and 15 controls in
      Virtual Reality (VR) environments reproducing usual daily living situations. In
      VR sessions, PD patients performed their actions worse than controls, in terms of
      time of execution in exploration and pointing, precision as objects avoiding, and
      in semantic incidental memory task. We observed clear differences of performances
      between on and off status medication, with a global worsening during off phase.
      Moreover, all six patients with motor fluctuations described visual
      hallucinations during off state, with occurrence of images not included in the
      virtual environment.

PMID- 19592765
TI  - Reactive Ocular and Balance Control in Immersive Visual Flows: 2D vs. 3D Virtual
      Stimuli.
AB  - The control of gaze and balance strongly depend on the processing of visual cues.
      The aim of this study is to assess the effects of the dynamic 2D and 3D visual
      inputs on the oculomotor and balance reactive control. Thirteen subjects were
      immersed in a virtual environment using 10 different 2D/3D visual flow
      conditions. Analysis of eye movement and postural adjustments shows that 2D and
      3D flows induce specific measurable behavioral responses.

PMID- 19592766
TI  - The co-definition of self: conversations in virtual reality.
AB  - Conversation analysis can take the form of a qualitative methodology for the
      exploration of discursive productions, whose main goal is the formulation of
      hypotheses for reading psychosocial interaction through descriptive models of
      interlocution. Therefore, in this study, conversations in a shared Virtual
      Environment have been analyzed in order to understand the specific structure,
      dynamics, and phenomenology of Virtual Reality effects on the "interactive micro
      chains" that constitute the communicative thread of daily experience.

PMID- 19592767
TI  - Mixed Reality for PTSD/TBI Assessment.
AB  - Mixed Reality (MR) refers to the blending of virtual content into the real world.
      Using MR, we create contextually meaningful scenarios in which users carry out
      tasks encountered in the presence of visual and aural distracters. Visual
      distracters can include subtle ones - people walking; and more abrupt ones -
      cartons falling. Aural distracters can include gentle ones - fans whirring; and
      more aggressive ones - automobiles backfiring. The intensity of these distracters
      can be dynamically controlled by a therapist or software that takes into account
      the patient's perceived level of stress. Intensity can also be controlled between
      experiences. For example, one may increase the stress level in a subsequent
      session, attempting to improve a person's tolerance. Assessment of progress
      includes psychophysical metrics (stress indicators) and the performance of tasks
      (accuracy and adherence to time constraints). By accurately capturing a patient's
      interaction with the environment in the context of simulation events, we can use
      MR as a tool for assessment and rehabilitation planning for individuals with
      stress-related injuries. This paper reports on the MR environment we have
      developed and its efficacy (realized and potential) for the assessment of post
      traumatic stress disorder (PTSD) with or without traumatic brain injury (TBI).

PMID- 19592768
TI  - Cost effectiveness of virtual reality graded exposure therapy with physiological
      monitoring for the treatment of combat related post traumatic stress disorder.
AB  - Virtual Reality Graded Exposure Therapy (VRGET) is an effective treatment for
      combat-related PTSD. We summarize the outcomes of a VRGET pilot study with 12
      participants who completed one to multiple combat tours in support of the War on
      Terrorism and who were subsequently diagnosed with combat-related PTSD. Details
      of the collaborative program amongst the Virtual Reality Medical Center (VRMC),
      Office of Naval Research, the Naval Medical Center San Diego (NMCSD) and the Navy
      Hospital Camp Pendleton are discussed as is the VRGET outcomes of significant
      reductions in PTSD symptoms severity. We also described the estimated cost
      effectiveness of VRGET for the treatment of combat-related PTSD, as contrasted to
      Treatment as Usual (TAU) for combat-related PTSD.

PMID- 19592769
TI  - Neuropsychological and virtual reality assessment in topographical
      disorientation.
AB  - Although literature does not provide a unique explanation, the importance of
      hippocampus for human topographical learning and orientation is assumed to be
      relevant by most of the authors. There is considerable evidence that the
      hippocampus is necessary for acquiring cognitive maps of allocentric space, which
      includes topographical knowledge of large-scale real environments. This study
      aimed to investigate neuropsychological and behavioral characteristics of
      topographical disorientation in a 71 years old patient, affected by an ischemic
      bilateral occipital lesion involving the hippocampus. Several assessment methods
      have been involved: neuropsychological test, paper and pencil test for the
      evaluation of topographical abilities, and a Virtual Reality tool. Experimental
      evidences for the value of an integrated evaluation approach in underlying
      spatial orientation difficulties are provided.

PMID- 19592770
TI  - A Rehabilitation Protocol for Empowering Spatial Orientation in MCI. A Pilot
      Study.
AB  - Spatial navigation is among the first cognitive functions to be impaired in
      Alzheimer's disease [1] and deficit in this domain is detectable earlier in
      patients with Mild Cognitive Impairment [2]. Since efficacy of cognitive training
      in persons with MCI was successfully assessed [3], we developed a multitasking
      training protocol using virtual environments for stimulating attention,
      perception and visuo-spatial cognition in order to empower spatial orientation in
      MCI. Two healthy elders were exposed to the training over a period of four weeks
      and both showed improved performances in attention and orientation after the end
      of the intervention.

PMID- 19592771
TI  - Semantic and gender priming in frontotemporal dementia.
AB  - Modifications of language processing can be observed both in normal aging and in
      the most common forms of degenerative dementia, such as Alzheimer's disease and
      the spectrum of frontotemporal dementias. The present experiment tests at the
      same time semantic and syntactic aspects of language processing in patients with
      frontotemporal dementia, using an online paradigm that allows researchers to
      evaluate the real linguistic competence of the patients.

PMID- 19592772
TI  - Assessment of inhibition deficits with the virtual classroom in children with
      traumatic brain injury: a pilot-study.
AB  - This study compared the performance of 8 children who have sustained a traumatic
      brain injury on the traditional VIGIL Continuous Performance Test and the
      Continuous Performance Test included in the Virtual Classroom. Results supported
      the hypothesis, showing that the Continuous Performance Test from the Virtual
      Classroom showed more sensitivity concerning inhibition deficits. More precisely,
      children showed more commission errors and longer reaction time. These results
      can be explained by the ecological character of the Virtual Classroom, meaning
      that this instrument is close to real-life experiences and requires more
      attention and inhibition resources.

PMID- 19592773
TI  - A NeuroVR based tool for cognitive assessment and rehabilitation of post-stroke
      patients: two case studies.
AB  - Neuropsychological disorders are common in stroke patients, ranging from an
      isolated impairment to impairment in multiple cognitive functions. The cognitive
      domains affected are in particular executive functions. These comprise planning,
      organising, conducting, assessing and controlling actions. Dual task abilities,
      that is the ability to perform successive or simultaneous tasks, are not easy to
      be evaluated and recovered by traditional paper and pencil methods, due to their
      ecological and contextual nature. NeuroVR 1.5 is a cost-free virtual reality
      platform based on open-source software, allowing professionals to easily modify a
      virtual world, to best suit the needs of the clinical setting.The present study
      was designed to develop and test a NeuroVR based tool for the rehabilitation of
      shifting of attention and action planning functions using tasks reminiscent of
      daily life tasks. We present the virtual environment and the cognitive procedure
      we developed, discussing two stroke patients case studies, which underwent an
      integrated neuropsychological and VR assessment.

PMID- 19592774
TI  - Designing an ecological and adaptable virtual task in the context of executive
      functions.
AB  - Brain damage is a major cause of disability that often leads to deficits in
      Executive Functions (EF) with dramatic consequences on activities of daily
      living. While rehabilitation approaches of the dysexecutive syndrome are still
      limited, Virtual Reality (VR) has shown its potential to propose innovative
      intervention strategies based on ecologically valid functional tasks. The purpose
      of this paper is to present the design process of the Therapeutic Virtual Kitchen
      (TVK) in which ecological and adaptable virtual tasks may be configured by the
      therapists for patients' assessment and rehabilitation. The outcomes of a
      preliminary test of feasibility among members of our laboratory and Kerpape
      Rehabilitation Center are reported and discussed.

PMID- 19592775
TI  - Cognitive Therapy Using Mixed Reality for Those Impaired by a Cerebrovascular
      Accident (CVA).
AB  - There is new research showing that interactive multimodal rehabilitation may
      enhance cognitive therapy after cerebrovascular accident. A well-designed Mixed
      Reality system provides a diverse, controllable and versatile therapeutic
      environment to help promote neural plasticity during recovery. In addition to
      stroke patients, there are other groups, such as those with traumatic brain
      injury (TBI) that could benefit from the system. Initial results, both paper-and
      pencil measures and physiological measures, in a trial with fourteen participants
      are discussed.

PMID- 19592776
TI  - Virtual reality for the upper limb motor training in stroke: a case report.
AB  - In this report we describe the effects of a virtual reality (VR) training
      addressed to the upper limb of a stroke patient. After 20 days of rehabilitation
      sessions consisting of physical therapy and VR rehabilitation, the subject was
      evaluated by means of kinematics and clinical scales. Results showed the
      improvement of paretic arm mobility, in terms of quantitative parameters and
      clinical scales, suggesting that VR training could represent a valuable tool to
      supplement the traditional rehabilitation provided by the physical therapist.

PMID- 19592778
TI  - Optimizing Clinical Training for the Treatment of PTSD Using Virtual Patients.
AB  - Adequate treatment of PTSD is a growing concern for the military. However, there
      is a shortage of qualified personnel available to apply this treatment. Virtual
      patient systems offer a novel technology to enhance the training needs of such
      health providers. This pilot project builds on previous work done with virtual
      patients and describes a novel scenario wherein a virtual patient is immersed
      within an exposure therapy simulation while a clinician interacts and guides the
      virtual patient through the recovery process using exposure therapy for PTSD.
      While this work is ongoing, preliminary results will be presented.

PMID- 19592777
TI  - A multimedia holistic rehabilitation method for patients after stroke.
AB  - The rehabilitation of patients after a stroke must provide polisensoric cognitive
      therapy. A specially designed computer/information system suits well to these
      requirements and offers a complementary and holistic treatment, which can be used
      in a rehabilitation center and later at the patient's home.

PMID- 19592779
TI  - Virtual Reality Therapy Controlled Study for War Veterans with PTSD. Preliminary
      Results.
AB  - More than 30 years after signing truces, there are still around 20,000 Portuguese
      war veterans that fill PTSD (Posttraumatic Stress Disorder) diagnose criteria.
      Despite many of them attending therapy, the outcome is not cheerful. In this way,
      a research protocol was devised to investigate the opportunity of adopting
      virtual reality exposure therapy (VRET) to reduce PTSD symptomathology. This
      protocol consists on a controlled study (VRET vs. traditional psychotherapy vs.
      waiting list), where in the VRET condition patients will be graded by being
      exposed to a virtual reality jungle scenario. The activating episodes, that are
      comprised of three cues (ambush, mortar blasting and waiting for injured rescue),
      are repeated 3 times each session. The cues' intensity and frequency increase
      from session to session. Patients are exposed to the VR world through a HMD (Head
      Mounted Display). This paper reports on the ongoing research where 4 VRET
      patients that filled CAPS DSM-IV PTSD criteria were assessed at pretreatment and
      at the middle of treatment (5th session). Results from IES and SCL-90R dimensions
      showed no statistical significant differences between assessments, with exception
      to obsession-compulsion dimension of SCL-90R (F(1;3)=21.235; p<.05), indicating a
      decrease in obsessive thoughts. However, through descriptive analysis, it was
      observed a reduction in all IES and SCL-90R dimensions, except for hostility and
      psychoticism of SCL-90R.

PMID- 19592780
TI  - Virtual worlds as a healing modality for returning soldiers and veterans.
AB  - Those who have served in recent conflicts face many challenges as they
      reintegrate into society. In addition to recovering from physical wounds,
      traumatic brain injury, and post-traumatic stress disorders, many soldiers also
      face basic psychological issues about who they are and how to find their place in
      a society that has not shared their experiences. To address these challenges, we
      have created a space that provides ongoing opportunities for healing activities,
      personal exploration and social camaraderie in an online virtual world, Second
      Life. In such worlds, where each avatar is controlled by a live individual,
      experiences can be unintuitive, uninviting, considered boring, or difficult to
      control. To counter this, we are implementing autonomous intelligent agent
      avatars that can be "on duty" 24/7, serving as guides and information
      repositories, making the space and activities easy to find and even personalized
      to the visitor's needs. We report the results of usability testing with an in
      world veterans' group. Tests comparing soldiers who use this space as part of
      their reintegration regimen compared to those who do not are being scheduled as
      part of the Army's Warriors in Transition program.

PMID- 19592781
TI  - Psychopathological issues of technological addiction: new diagnostic criteria for
      addiction.
AB  - All forms of addiction (drug addiction, food addiction, sexual addiction,
      technological addiction, work addiction) are syndromic conditions characterized
      by a recurrent and reiterated search for pleasure derived from a specific
      dependence behavior, associated with abuse, craving, clinically significant
      stress, and compulsive dependence actions despite the possible negative
      consequences. The purpose of this article is to propose a new diagnostic criteria
      of addiction.

PMID- 19592782
TI  - A new protocol test for physical activity research in obese children (etiobe
      project).
AB  - A new protocol is presented to validate TIPS (portable physiological monitoring
      device designed by I3BH that can get respiration, ecg and activity of the
      patient) for physical habits detection. Physiological and activity parameters and
      data from questionnaires have been acquired from a group of obese & non-obese
      children (n=20). Children completed activities from sedentary level to vigorous
      level. Preliminary results show variability on the response of children's effort
      and feasibility of TIPS platform as an ambulatory tool.

PMID- 19592783
TI  - Rehabilitation as empowerment: the role of advanced technologies.
AB  - Rehabilitation is placing increasing emphasis on the construct of empowerment as
      the final goal of any treatment approach. This reflects a shift in focus from
      deficits and dependence to assets and independence. According to this approach,
      rehabilitation should aim to improve the quality of the life of the individual by
      means of effective support to his/her activity and interaction. Here we suggest
      that advanced technologies can play a significant role in this process. By
      enhancing the experienced level of "Presence" - the non-mediated perception of
      successfully transforming intentions into action - these emerging technologies
      can foster optimal experiences (Flow) and support the empowerment process.
      Finally, we describe the "NeuroVR" system (http://www.neurovr.org) as an example
      of how advanced technologies can be used to support Presence and Flow in the
      rehabilitation process.

PMID- 19592784
TI  - Robotic assistance for upper extremity training after stroke.
AB  - There has been a rapid increase in the past decade in the number of robotic
      devices that are being developed to assist in movement rehabilitation of the
      upper extremity following stroke. Many of these devices have produced positive
      clinical results. Yet, it is still not well understood how these devices enhance
      movement recovery, and whether they have inherent therapeutic value that can be
      attributed to their robotic properties per se. This chapter reviews the history
      of robotic assistance for upper extremity training after stroke and the current
      state of the field. Future advances in the field will likely be driven by
      scientific studies focused on defining the behavioral factors that influence
      motor plasticity.

PMID- 19592786
TI  - Assessment and treatment of the upper limb by means of virtual reality in post
      stroke patients.
AB  - The disability deriving from stroke impacts heavily on the economic and social
      aspects of western countries because stroke survivors commonly experience various
      degrees of autonomy reduction in the activities of daily living. Recent
      developments in neuroscience, neurophysiology and computational science have led
      to innovative theories about the brain mechanisms of the motor system.
      Thereafter, innovative, scientifically based therapeutic strategies have
      initially arisen in the rehabilitation field. Promising results from the
      application of a virtual reality based technique for arm rehabilitation are
      reported.

PMID- 19592785
TI  - Robotic assisted rehabilitation in Virtual Reality with the L-EXOS.
AB  - This study presents the evaluation results of a clinical trial of robotic
      assisted rehabilitation in Virtual Reality performed with the PERCRO L-Exos
      (Light-Exoskeleton) system, which is a 5-DoF force-feedback exoskeleton for the
      right arm. The device has demonstrated itself suitable for robotic arm
      rehabilitation therapy when integrated with a Virtual Reality (VR) system. Three
      different schemes of therapy in VR were tested in the clinical evaluation trial,
      which was conducted on a group of nine chronic stroke patients at the Santa
      Chiara Hospital in Pisa-Italy. The results of this clinical trial, both in terms
      of patients performance improvements in the proposed exercises and in terms of
      improvements in the standard clinical scales which were used to monitor patients
      receovery are reported and discussed. The evaluation both pre and post-therapy
      was carried out with both clinical and quantitative kinesiologic measurements.
      Statistically significant improvements were found in terms of Fugl-Meyer scores,
      Ashworth scale, increments of active and passive ranges of motion of the impaired
      limb, and quantitative indexes, such as task time and error.

PMID- 19592787
TI  - The rehabilitation gaming system: a review.
AB  - Stroke will become one of the main burdens of disease and loss of quality of life
      in the near future. However, we still have not found rehabilitation approaches
      that can scale up so as to face this challenge. Virtual reality based therapy
      systems are a great promise for directly addressing this challenge. Here we
      review different approaches that are based on this technology, their assumptions
      and clinical impact. We will focus on virtual reality based rehabilitation
      systems that combine hypotheses on the aftermath of stroke and the neuronal
      mechanisms of recovery that directly aims at addressing this challenge. In
      particular we will analyze the, so called, Rehabilitation Gaming System (RGS)
      that proposes the use of non-invasive multi-modal stimulation to activate intact
      neuronal systems that provide direct stimulation to motor areas affected by brain
      lesions. The RGS is designed to engage the patients in task specific training
      scenarios that adapt to their performance, allowing for an individualized
      training of graded difficulty and complexity. Although RGS stands for a generic
      rehabilitative approach it has been specifically tested for the rehabilitation of
      motor deficits of the upper extremities of stroke patients. In this chapter we
      review the main foundations and properties of the RGS, and report on the major
      findings extracted from studies with healthy and stroke subjects. We show that
      the RGS captures qualitative and quantitative data on motor deficits, and that
      this is transferred between real and VR tasks. Additionally, we show how the RGS
      uses the detailed assessment of the kinematics and performance of stroke patients
      to individualize the treatment. Subsequently, we will discuss how real-time
      physiology can be used to provide additional measures to assess the task
      difficulty and subject engagement. Finally, we report on preliminary results of
      an ongoing longitudinal study on acute stroke patients.

PMID- 19592788
TI  - Virtual reality and gaming systems to improve walking and mobility for people
      with musculoskeletal and neuromuscular conditions.
AB  - Improving walking for individuals with musculoskeletal and neuromuscular
      conditions is an important aspect of rehabilitation. The capabilities of
      clinicians who address these rehabilitation issues could be augmented with
      innovations such as virtual reality gaming based technologies. The chapter
      provides an overview of virtual reality gaming based technologies currently being
      developed and tested to improve motor and cognitive elements required for
      ambulation and mobility in different patient populations. Included as well is a
      detailed description of a single VR system, consisting of the rationale for
      development and iterative refinement of the system based on clinical science.
      These concepts include: neural plasticity, part-task training, whole task
      training, task specific training, principles of exercise and motor learning,
      sensorimotor integration, and visual spatial processing.

PMID- 19592789
TI  - Virtual reality environments to enhance upper limb functional recovery in
      patients with hemiparesis.
AB  - Impairments in reaching and grasping have been well-documented in patients with
      post-stroke hemiparesis. Patients have deficits in spatial and temporal
      coordination and may use excessive trunk displacement to assist arm transport
      during performance of upper limb tasks. Studies of therapeutic effectiveness have
      shown that repetitive task-specific practice may improve motor function outcomes.
      Movement retraining may be optimized when done in virtual reality (VR)
      environments. Environments created with VR technology can incorporate elements
      essential to maximize motor learning, such as repetitive and varied task
      practice, performance feedback and motivation. Haptic technology can also be
      incorporated into VR environments to enhance the user's sense of presence and to
      make motor tasks more ecologically relevant to the participant. As a first step
      in the validation of the use of VR environments for rehabilitation, it is
      necessary to demonstrate that movements made in virtual environments are similar
      to those made in equivalent physical environments. This has been verified in a
      series of studies comparing pointing and reaching/grasping movements in physical
      and virtual environments. Because of the attributes of VR, rehabilitation of the
      upper limb using VR environments may lead to better rehabilitation outcomes than
      conventional approaches.

PMID- 19592790
TI  - Virtual reality to maximize function for hand and arm rehabilitation: exploration
      of neural mechanisms.
AB  - Stroke patients report hand function as the most disabling motor deficit. Current
      evidence shows that learning new motor skills is essential for inducing
      functional neuroplasticity and functional recovery. Adaptive training paradigms
      that continually and interactively move a motor outcome closer to the targeted
      skill are important to motor recovery. Computerized virtual reality simulations
      when interfaced with robots, movement tracking and sensing glove systems, are
      particularly adaptable, allowing for online and offline modifications of task
      based activities using the participant's current performance and success rate. We
      have developed a second generation system that can exercise the hand and the arm
      together or in isolation and provide for both unilateral and bilateral hand and
      arm activities in three-dimensional space. We demonstrate that by providing
      haptic assistance for the hand and arm and adaptive anti-gravity support, the
      system can accommodate patients with lower level impairments. We hypothesize that
      combining training in virtual environments (VE) with observation of motor actions
      can bring additional benefits. We present a proof of concept of a novel system
      that integrates interactive VE with functional neuroimaging to address this
      issue. Three components of this system are synchronized, the presentation of the
      visual display of the virtual hands, the collection of fMRI images and the
      collection of hand joint angles from the instrumented gloves. We show that
      interactive VEs can facilitate activation of brain areas during training by
      providing appropriately modified visual feedback. We predict that visual
      augmentation can become a tool to facilitate functional neuroplasticity.

PMID- 19592791
TI  - Robot therapy for stroke survivors: proprioceptive training and regulation of
      assistance.
AB  - Robot therapy seems promising with stroke survivors, but it is unclear which
      exercises are most effective, and whether other pathologies may benefit from this
      technique. In general, exercises should exploit the adaptive nature of the
      nervous system, even in chronic patients. Ideally, exercise should involve
      multiple sensory modalities and, to promote active subject participation, the
      level of assistance should be kept to a minimum. Moreover, exercises should be
      tailored to the different degrees of impairment, and should adapt to changing
      performance. To this end, we designed three tasks: (i) a hitting task, aimed at
      improving the ability to perform extension movements; (ii) a tracking task, aimed
      at improving visuo-motor control; and (iii) a bimanual task, aimed at fostering
      inter-limb coordination. All exercises are conducted on a planar manipulandum
      with two degrees of freedom, and involve alternating blocks of exercises
      performed with and without vision. The degree of assistance is kept to a minimum,
      and adjusted to the changing subject's performance. All three exercises were
      tested on chronic stroke survivors with different levels of impairment. During
      the course of each exercise, movements became faster, smoother, more precise, and
      required decreasing levels of assistive force. These results point to the
      potential benefit of that assist-as-needed training with a proprioceptive
      component in a variety of clinical conditions.

PMID- 19592792
TI  - Advances in wearable technology for rehabilitation.
AB  - Assessing the impact of rehabilitation interventions on the real life of
      individuals is a key element of the decision-making process required to choose a
      rehabilitation strategy. In the past, therapists and physicians inferred the
      effectiveness of a given rehabilitation approach from observations performed in a
      clinical setting and self-reports by patients. Recent developments in wearable
      technology have provided tools to complement the information gathered by
      rehabilitation personnel via patient's direct observation and via interviews and
      questionnaires. A new generation of wearable sensors and systems has emerged that
      allows clinicians to gather measures in the home and community settings that
      capture patients' activity level and exercise compliance, the effectiveness of
      pharmacological interventions, and the ability of patients to perform efficiently
      specific motor tasks. Available unobtrusive sensors allow clinical personnel to
      monitor patients' movement and physiological data such as heart rate, respiratory
      rate, and oxygen saturation. Cell phone technology and the widespread access to
      the Internet provide means to implement systems designed to remotely monitor
      patients' status and optimize interventions based on individual responses to
      different rehabilitation approaches. This chapter summarizes recent advances in
      the field of wearable technology and presents examples of application of this
      technology in rehabilitation.

PMID- 19592793
TI  - Brain-computer interfaces and neurorehabilitation.
AB  - A brain-computer interface (BCI) directly uses brain-activity signals to allow
      users to operate the environment without any muscular activation. Thanks to this
      feature, BCI systems can be employed not only as assistive devices, but also as
      neurorehabilitation tools in clinical settings. However, several critical issues
      need to be addressed before using BCI in neurorehabilitation, issues ranging from
      signal acquisition and selection of the proper BCI paradigm to the evaluation of
      the affective state, cognitive load and system acceptability of the users. Here
      we discuss these issues, illustrating how a rehabilitation program can benefit
      from BCI sessions, and summarize the results obtained so far in this field. Also
      provided are experimental data concerning two important topics related to BCI
      usability in rehabilitation: the possibility of using dry electrodes for EEG
      acquisition, and the monitoring of psychophysiological effects during BCI tasks.

PMID- 19592794
TI  - Why is music effective in rehabilitation?
AB  - In this chapter a conceptual foundation of employing music in rehabilitation is
      highlighted. The basic assumption is that, when a person is involved in
      performing or listening to music, she has a comprehensive experience in which
      several mental registers are activated simultaneously. The specific effect of
      music is to trigger a coordinated action of motor, visuospatial and verbal
      mechanisms. Thanks to the synergic activation of these mechanisms, music can
      stimulate, support and driven the mental functions to be rehabilitated.

PMID- 19592795
TI  - Computer-guided mental practice in neurorehabilitation.
AB  - Motor imagery is the mental simulation of a movement without motor output. In
      recent years, there has been growing interest towards the application of motor
      imagery-based training, or "mental practice", in stroke rehabilitation. We have
      developed a virtual reality prototype (the VR Mirror) to support patients in
      performing mental practice. The VR Mirror displays a three-dimensional simulation
      of the movement to be imagined, using data acquired from the healthy arm. We
      tested the system with nine post-stroke patients with chronic motor impairment of
      the upper limb. After eight weeks of training with the VR Mirror, remarkable
      improvement was noted in three cases, slight improvement in two cases, and no
      improvement in four cases. All patients showed a good acceptance of the
      procedure, suggesting that virtual reality technology can be successfully
      integrated in mental practice interventions.

PMID- 19592797
TI  - Telerehabilitation: enabling the remote delivery of healthcare, rehabilitation,
      and self management.
AB  - Telerehabilitation refers to the use of Information and Communication
      Technologies (ICT) to provide rehabilitation services to people remotely in their
      homes or other environments. By using ICT, client access to care can be improved
      and the reach of clinicians can extend beyond the physical walls of a traditional
      healthcare facility, thus expanding continuity of care to persons with disabling
      conditions. The concept of telecare, when telerehabilitation is used to deliver
      services to clients in their homes or other living environments, empowers and
      enables individuals to take control of the management of their medical needs and
      interventions by enabling personalized care, choice and personal control. A wide
      variety of assessment and treatment interventions can be delivered to clients
      using remote monitoring systems, robotic and virtual reality technologies, and
      synchronized collaboration with online material. This chapter will present a
      brief history of telerehabilitation and telecare and offer an overview of the
      technology used to provide remote rehabilitation services. Emphasis will be given
      to the importance of human factors and user-centered design in the planning,
      development, and implementation of telerehabilitation systems and programs. The
      issue of self-care in rehabilitation and self-management will be discussed along
      with the rationale for how telerehabilitation can be used to promote client self
      care and self-management. Two case studies of real-world telerehabilitation
      systems will be given, with a focus on how they were planned and implemented so
      as to maximize their potential benefits. The chapter will close with a discussion
      of obstacles and challenges facing telerehabilitation and suggestions for ways to
      promote its growth in use and acceptance.

PMID- 19592796
TI  - Postural and spatial orientation driven by virtual reality.
AB  - Orientation in space is a perceptual variable intimately related to postural
      orientation that relies on visual and vestibular signals to correctly identify
      our position relative to vertical. We have combined a virtual environment with
      motion of a posture platform to produce visual-vestibular conditions that allow
      us to explore how motion of the visual environment may affect perception of
      vertical and, consequently, affect postural stabilizing responses. In order to
      involve a higher level perceptual process, we needed to create a visual
      environment that was immersive. We did this by developing visual scenes that
      possess contextual information using color, texture, and 3-dimensional
      structures. Update latency of the visual scene was close to physiological
      latencies of the vestibulo-ocular reflex. Using this system we found that even
      when healthy young adults stand and walk on a stable support surface, they are
      unable to ignore wide field of view visual motion and they adapt their postural
      orientation to the parameters of the visual motion. Balance training within our
      environment elicited measurable rehabilitation outcomes. Thus we believe that
      virtual environments can serve as a clinical tool for evaluation and training of
      movement in situations that closely reflect conditions found in the physical
      world.

PMID- 19592798
TI  - Socially assistive robotics for stroke and mild TBI rehabilitation.
AB  - This paper describes an interdisciplinary research project aimed at developing
      and evaluating effective and user-friendly non-contact robot-assisted therapy,
      aimed at in-home use. The approach stems from the emerging field of social
      cognitive neuroscience that seeks to understand phenomena in terms of
      interactions between the social, cognitive, and neural levels of analysis. This
      technology-assisted therapy is designed to be safe and affordable, and relies on
      novel human-robot interaction methods for accelerated recovery of upper-extremity
      function after lesion-induced hemiparesis. The work is based on the combined
      expertise in the science and technology of non-contact socially assistive
      robotics and the clinical science of neurorehabilitation and motor learning,
      brought together to study how to best enhance recovery after stroke and mild
      traumatic brain injury. Our approach is original and promising in that it
      combines several ingredients that individually have been shown to be important
      for learning and long-term efficacy in motor neurorehabilitation: (1) intensity
      of task specific training and (2) engagement and self-management of goal-directed
      actions. These principles motivate and guide the strategies used to develop novel
      user activity sensing and provide the rationale for development of socially
      assistive robotics therapy for monitoring and coaching users toward personalized
      and optimal rehabilitation programs.

PMID- 19592799
TI  - Moving beyond single user, local virtual environments for rehabilitation.
AB  - The rapid development of Virtual Reality-based technologies over the past decade
      is both an asset and a challenge for neuro-rehabilitation. The availability of
      novel technologies that provide interactive, functional simulations with
      multimodal feedback enable clinicians to achieve traditional therapeutic goals
      that would be difficult, if not impossible, to attain via conventional therapy.
      They also lead to the creation of completely new clinical paradigms which would
      have been hard to achieve in the past. In applications of rehabilitation for both
      motor and cognitive deficits the main focus of much of the early exploratory
      research has been to investigate the use of virtual reality as an assessment
      tool. To date such environments are primarily: (a) single user (i.e., designed
      for and used by one clinical client at a time) and (b) used locally within a
      clinical or educational setting. More recently, researchers have begun the
      development of new and more complex VR-based approaches according to two
      dimensions: the number of users and the distance between the users. Driven by a
      push-pull phenomenon, the original approach has now expanded to three additional
      avenues: multiple users in co-located settings; single users in remote locations;
      and multiple users in remote locations. After a presentation of examples that
      illustrate theses various approaches, we will conclude in addressing questions
      and ethical considerations raised by this evolution in the use of virtual
      environments in rehabilitation.

PMID- 19592800
TI  - Milestones of the IMIA-NI history and future directions.
AB  - IMIA-NI's past achievements are reflected upon in the context of its current
      strategic directions. Two key historical milestones are described in some detail,
      the ISO Reference terminology model for nursing and the International Nursing
      Minimum Data Set development project, as this work is continuing to influence
      future directions in health and nursing informatics. Current features of our
      health care environment are explored noting the current desire of most nations to
      implement electronic health records (EHRs) and its relationship with IMIA-NI's
      strategic directions. Nurses can play their part by working collaboratively,
      converting their knowledge into computer processable formats, establishing the
      necessary professional knowledge governance infrastructure and lobbying key
      decision makers to establish national infrastructures that will enable the
      adoption and optimum use of EHRs.

PMID- 19592801
TI  - A method to improve a job process at a hospital using the "unit process flow
      chart".
AB  - The development of methods to improve the quality of services provided at
      hospitals has been essential owing to the inadequacy of arrangements for standard
      procedures and the inadequacy of work instructions based on such procedures. In
      this paper, we propose a method that involves the following steps: description of
      the job process, analysis of the causes of incidents, and the planning of
      improvements for the relevant job process. This method describes a healthcare
      process using a set of unit process flow charts (UPFCs), which are structured and
      standardized modules represented in the form of flow charts that elucidate the
      elements of jobs. Describing a job in this manner allows for an appropriate and
      in-depth analysis of the causes of incidents that occur during a job process,
      owing to the fact that the structure and description of the characteristics of
      relevant unit processes are properly designed. In this paper, we provide a
      detailed explanation of how this method was developed. Lastly, we apply the
      method to actual cases at a hospital to illustrate its effectiveness in
      comparison with the systems that are currently in place.

PMID- 19592802
TI  - ICT supporting nurses and physicians in hospitals: results of a comparative
      survey in Austria and Germany.
AB  - This study aimed to compare the use of clinical information systems, particularly
      for nursing, in Austria and Germany. In 2007, all acute care hospitals in both
      countries received questionnaires with identical questions. 12.4% in Germany and
      34.6% in Austria responded. The surveys revealed a consistent higher usage of
      clinical IT in Austrian than in German hospitals. It also included a significant
      difference in the percentage of electronic nursing records in use. These findings
      correspond with a significantly higher number of PC workstations on the wards.
      Despite these differences, Austrian and German hospitals reported a nearly
      identical IT budget. Factors which might have influenced the wider use of
      clinical IT are a re-focus on clinical matters after rigorous organisational
      changes, legal constraints and a general IT-friendly climate in Austria.

PMID- 19592803
TI  - Benchmarking by the RAFAELA Patient Classification system - a descriptive study
      of optimal nursing intensity levels.
AB  - The overall aim of the RAFAELA system is that the personnel resources should be
      in balance with the patients' caring needs, i.e. when the nursing intensity per
      nurse is on the optimal level of the unit. The RAFAELA system consists of three
      parts: the OPCq (Oulu Patient Classification Qualisan) instrument for measuring
      the nursing intensity, registration of the daily nursing resources and the
      PAONCIL (Professional Assessment of Optimal Nursing Care Intensity Level) method.
      The aim of this paper is (1) to describe the structure of benchmarking with the
      RAFAELA system and (2) to present comparisons of optimal nursing intensity levels
      in Finnish hospitals by using data from RAFAELA benchmarking reports in 2001.
      Totally 86 wards from 14 different hospitals in Finland took part in the study,
      the optimal nursing intensity had been decided for 53 wards. Data was analyzed
      using descriptive statistics. The average workload was on adult wards 25.2 NCI
      points per nurse. The optimal NCI was exceeded during 48% of the days and under
      during 22% of the days. An imbalance between nursing intensity and personnel
      resources clearly affects the care quality and the results. Benchmarking with the
      RAFAELA system provides nurse managers with many opportunities in their decision
      processes in human resource management.

PMID- 19592804
TI  - Oulu Patient Classification instrument within primary health care.
AB  - As patients have become older their care needs have increased, and this has
      consequences for the working conditions within primary health care. OBJECTIVES:
      The aim of this study was to evaluate, whether the OPC instrument, which has been
      developed for hospital care, is valid and useful within primary healthcare for
      older people. MATERIALS AND METHODS: Reliability and validity testing of the OPC
      instrument was carried out at a health care centre in Eastern Finland spring
      2004. A total number of 92 questionnaires were handed out, and the response rate
      was 67% (n=61) in order to test the validity. The inter-rater reliability was
      tested through parallel classification. A total number of 860 patient's were
      classified; in total 1722 classifications ware done. Cohens Kappa was chosen as
      the measurement for the consensus between the nurses' classification. RESULT: The
      consensus of the NI scores in total (OPC points) was 71%. The consensus measured
      with Kappa (k) showed a strong (0.65) consensus degree. DISCUSSION: It can be
      said that the OPC instrument achieved a high enough reliability and validity in
      order to be seen as a reliable and useful instrument to measure the NCI within
      primary healthcare for the elderly. CONCLUSION: The OPC instrument can be seen as
      providing a fairly comprehensive view of the patient's caring needs, without
      claiming to be covering everything.

PMID- 19592805
TI  - The linkage of nursing assessment and nursing workload.
AB  - The automated linkage of nursing assessment, nursing interventions, nursing
      workload measurement, and outcomes supports the user in practice and increases
      the explanatory power of nursing data, e.g. in DRG systems. Practice relevant
      data should therefore be available for the different needs for information by
      policy, management, research and training. To this end, two projects have
      gradually linked the outcome-oriented nursing assessment instrument AcuteCare
      (ePA-AC) and the nursing intervention and workload measurement system LEP Nursing
      3 with each other.

PMID- 19592806
TI  - Nursing informatics; is IT for all nurses?
AB  - Given the definition if nursing informatics it should be a core activity for all
      nurses, and seen as a tool to support high quality care giving. Three studies
      reported in this paper show that this is not the case. Qualified nurses are
      perceived as having poor skills and knowledge, and as being resistant to IT as it
      takes them away from patient care. Educators share this lack of knowledge, and
      neither academics nor students consider nursing informatics to be a clinical
      skill. In order to use computers while on placement students were found to need
      confidence in their skills, and to feel that the use of computers was encouraged.
      Socialisation into the profession is an important part of nurse education, and
      currently students are being socialised into a professional role where they are
      not encouraged to use computers, or to consider their use to be a key nursing
      task. If nursing informatics is to truly become a way of improving patient care
      this needs to be changed, and pre-registration education is a key place to start
      to bring this change about.

PMID- 19592807
TI  - The online Managed Knowledge Network that shares knowledge for eHealth in NHS
      Scotland.
AB  - The Managed Knowledge Network (MKN) for Nurses, Midwives and the Allied Health
      Professions (NMAHPs) in NHS Scotland was launched in November 2007. The online
      portal supports the NMAHP network to manage its knowledge and information sources
      that facilitate engagement with the national eHealth programme and realisation of
      benefits that eHealth offers to improve healthcare and service delivery. It is an
      integrated change management and knowledge management initiative. Web2
      technologies support the social networking side of knowledge management and
      learning, allowing people to contact each other and collaborate. MKN resources
      are managed within the e-Library also giving access to over 5,000 online journals
      and over 500 bibliographic databases.

PMID- 19592808
TI  - Key elements of successful care process of patients with heart symptoms in an
      emergency care - could an ERP system help?
AB  - The aim of the study was to identify key elements of successful care process of
      patients with heart symptoms from the nursing management viewpoint in an
      emergency care. Through these descriptions, we aimed at identifying possibilities
      for using enterprise resource planning (ERP) systems to support decision making
      in emergency care. Hospitals are increasingly moving to process-based workings
      and at the same time new information system in healthcare are developed and
      therefore it is essential to understand the strengths and weaknesses of current
      processes better. A qualitative descriptive design using critical incident
      technique was employed. Critical Incidents were collected with an open-ended
      questionnaire. The sample (n=50), 13 head nurses and 37 registered nurses, was
      purposeful selected from three acute hospitals in southern Finland. The process
      of patients with heart symptoms in emergency care was described. We identified
      three competence categories where special focus should be placed to achieve
      successful process of patients with heart symptoms: process-oriented
      competencies, personal/management competencies and logistics oriented
      competencies. Improvement of decision making requires that the care processes are
      defined and modeled. The research showed that there are several happenings in
      emergency care where an ERP system could help and support decision making. These
      happenings can be categorized in two groups: 1) administrative related happenings
      and 2) patient processes related happenings.

PMID- 19592809
TI  - Nurses using futuristic technology in today's healthcare setting.
AB  - Human computer interaction (HCI) equates nurses using voice assisted technology
      within a clinical setting to document patient care real time, retrieve patient
      information from care plans, and complete routine tasks. This is a reality
      currently utilized by clinicians today in acute and long term care settings.
      Voice assisted documentation provides hands & eyes free accurate documentation
      while enabling effective communication and task management. The speech technology
      increases the accuracy of documentation, while interfacing directly into the
      electronic health record (EHR). Using technology consisting of a light weight
      headset and small fist size wireless computer, verbal responses to easy to follow
      cues are converted into a database systems allowing staff to obtain
      individualized care status reports on demand. To further assist staff in their
      daily process, this innovative technology allows staff to send and receive pages
      as needed. This paper will discuss how leading edge and award winning technology
      is being integrated within the United States. Collaborative efforts between
      clinicians and analyst will be discussed reflecting the interactive design and
      build functionality. Features such as the system's voice responses and directed
      cues will be shared and how easily data can be documented, viewed and retrieved.
      Outcome data will be presented on how the technology impacted organization's
      quality outcomes, financial reimbursement, and employee's level of satisfaction.

PMID- 19592810
TI  - Scenario-based design of an ICT platform for mobile information services in
      ambulatory care nursing.
AB  - The field of ambulatory care nursing is rapidly growing due to rising health care
      costs and the demographic development. Against this background, the VitaBIT
      project started in 2007 with the objective of designing an ICT platform for the
      safe application of mobile information services in ambulatory care nursing.
      Communication and secure information exchange between all parties involved in the
      care process are also guaranteed. The article explains the project's current
      approach to develop a user-oriented solution using the design steps implied by
      ISO 13407. Even if a technology is developed and formally tested to be highly
      usable there exists no guarantee that this will lead to acceptance. That is the
      reason why end users are involved in all the project stages and serve as testers
      of prototypes in VitaBIT.

PMID- 19592811
TI  - Using personas and prototypes to define nurses' requirements for a novel patient
      monitoring display.
AB  - Software is often designed based on the designer's mental model rather than the
      user's. To correct this, we created personas (archetypes) of nurses using
      observations and semi-structured interviews. We developed and evaluated patient
      monitoring display prototypes for each persona. Among 11 ICU nurses, we found
      that the majority of nurses preferred a parsimonious data representation with
      large numbers and waveforms allowing all relevant data to be visible. Using
      personas and paper prototypes is an inexpensive and effective way to assess
      nurses' requirements and design preferences.

PMID- 19592812
TI  - From e-Health to integrated health care: theory and practice.
AB  - INTRODUCTION: Health care organizations and providers are under constant pressure
      to do more with less. On the other hand, users of health care services are faced
      with problems due to errors in communication between professionals, fragmentation
      of care and gaps in the continuum of care. OBJECTIVES: The aim of this study was
      to explore the meaning of the term 'integration' with reference to health, and
      underscore the need for integration of the healthcare systems. METHODS: The
      literature study approach was employed. The first part underlines the
      conceptualizations of integration and methods for healthcare integration in
      practice. In the second part, the current situation in Slovenia in this field is
      outlined. RESULTS: Activities are currently underway for laying down the
      fundamental normative infrastructure and legal bases for implementation of the
      eHealth projects, establishing a common health information network, and creating
      the bases for a standardized electronic health medical record. CONCLUSIONS: In
      the 'top-down' method, we concentrate mainly on general organizational changes
      for the purpose of achieving coherence and optimization. Projects that focus on
      the needs of individual patient groups belong under the 'bottom-up' process of
      integration. To achieve an optimal degree of integration, all health
      professionals have to play a key role in formulating the strategy of integration
      at all levels of healthcare.

PMID- 19592814
TI  - Strategic management of health care information systems: nurse managers'
      perceptions.
AB  - The aim of this study is to describe nurse managers' perceptions of the strategic
      management of information systems in health care. Lack of strategic thinking is a
      typical feature in health care and this may also concern information systems. The
      data for this study was collected by eight focus group interviews including
      altogether 48 nurse managers from primary and specialised health care. Five main
      categories described the strategic management of information systems in health
      care; IT as an emphasis of strategy; lack of strategic management of information
      systems; the importance of management; problems in privacy protection; and costs
      of IT. Although IT was emphasised in the strategies of many health care
      organisations, a typical feature was a lack of strategic management of
      information systems. This was seen both as an underutilisation of IT
      opportunities in health care organisations and as increased workload from nurse
      managers' perspective. Furthermore, the nurse managers reported that
      implementation of IT strengthened their managerial roles but also required
      stronger management. In conclusion, strategic management of information systems
      needs to be strengthened in health care and nurse managers should be more
      involved in this process.

PMID- 19592815
TI  - Observations on sustainable and ubiquitous healthcare informatics from Florence
      Nightingale.
AB  - As nurses around the world prepare to celebrate the centenary of the death of
      Florence Nightingale in 2010 this paper reviews her work on using information,
      especially statistics, to analyze and manage patient care and links that to
      current developments in informatics. It then examines assistive technologies and
      how they may impact on nursing practice in the future and links these
      developments to the writings of Florence Nightingale. The paper concludes by
      suggesting that in progressing towards sustainable and ubiquitous healthcare
      informatics we need to study history in order to learn from the lessons of
      Florence Nightingale and other healthcare pioneers.

PMID- 19592816
TI  - Review of an automated rostering system from a nurse manager's perspective.
AB  - In 2007 the Rostering Project Team (RPT) completed an audit of nursing managers
      using computerised rostering system. This audit highlighted the overall lack of
      rostering experience among the participants and the need for formalised education
      in this area.

PMID- 19592813
TI  - Usability testing of a web-based tool for managing open shifts on nursing units.
AB  - Using observational and interview approaches, we evaluated the usability of a web
      based communication tool that allows managers to announce open work shifts and
      staff to request work shifts. We used Morae software to record screen shots and
      study participants' (4 Nurse Managers, 3 Registered Nurses and 3 Patient Care
      Technicians) utterances during system use. Although features and functions used
      and patterns of use varied by role and individual, all participants found the
      system easy to use. Use of a particular function depended upon how effective the
      user perceived the function to be for the task that they wished to accomplish.
      User satisfaction was achieved when an effective function also allowed them to
      meet their task goal efficiently.

PMID- 19592817
TI  - Using computers for planning and evaluating nursing in the health care services.
AB  - This paper describes that the nurses attitudes, using and motivation towards the
      computer usage significantly influenced by area of nursing/health care service.
      Today most of the nurses traditionally document patient information in a medical
      record using pen and paper. Most nursing administrators not currently involved
      with computer applications in their settings are interested in exploring whether
      technology could help them with the day-to-day and long - range tasks of planning
      and evaluating nursing services. The results of this investigation showed that
      respondents (nurses), as specialists and nursing informatics, make their activity
      well: they had "positive" attitude towards computers and "good" or "average"
      computer skills. The nurses overall computer attitude did influence by the age of
      the nurses, by sex, by professional qualification. Younger nurses acquire
      informatics skills while in nursing school and are more accepting of computer
      advancements. The knowledge about computer among nurses who don't have any
      training in computers' significantly differs, who have training and using the
      computer once a week or everyday. In the health care services often are using the
      computers and the automated data systems, data for the statistical information
      (visit information, patient information) and billing information. In nursing
      field often automated data systems are using for statistical information, billing
      information, information about the vaccination, patient assessment and patient
      classification.

PMID- 19592818
TI  - Initiatives to support the emergence of nursing informatics.
AB  - A major event, such as a nursing informatics conference or course has been used
      successfully as an impetus to gather nurses interested in informatics together.
      This paper reflects on a 2008 nursing informatics event held in Singapore and the
      author's previous experiences with initiatives to support the emergence of
      nursing informatics in countries without a strong nursing informatics presence.
      Possible next steps and potential barriers are identified. It is hoped that
      countries new to informatics, and without an established nursing informatics
      group may gather ideas on how to better support nursing informatics involvement.

PMID- 19592819
TI  - Is PDA good for complex documentation in healthcare?
AB  - The screen interface has been believed to be the major barrier for the adoption
      of mobile devices with small display in healthcare. The study objective was to
      evaluate nurses' perception of the ease of use and usefulness of PDA application,
      designed with customerized design principles. The PDA application consisted of 18
      categories composed of 262 questions over 63 screens, which was designed based on
      a 21-page Chinese version of the interRAI MDS-HC homecare assessment tool. A WiFi
      Palm<sup>(c)</sup>-based PDA was used. A convenience sample of 60 subjects was
      invited for evaluation in terms of Davis' Technology Acceptance Model. Results
      show that close to 95% and 93% of the subjects agreed, overall, the system was
      easy to use and useful for their work. We conclude that PDAs can be improved and
      managed to achieve to a very high usability with right interface design
      principles.

PMID- 19592820
TI  - A pilot study exploring the clinical benefits when using a Mobile Clinical
      Assistant, the Motion C5 in medical wards.
AB  - Hand held computers and point of care devices have been identified as tools that
      can support more efficient safe care delivery. This paper describes a pilot which
      evaluates this technology for usage by the nursing and the wider clinical team .
      The pilot aims to explore the clinical benefits of using the newest Mobile Point
      of Care device, the Motion C5 Mobile Clinical Assistant (MCA), launched in late
      Oct 2007. The pilot involved 9 clinicians, sharing 6 devices across 7 wirelessed
      medical ward areas. The findings were reviewed qualitatively, and thematically
      analysed. The pilot highlighted significant benefits, the support of the delivery
      safer more effective care to patients in NHS Lothian.

PMID- 19592821
TI  - How different technologies can fit nursing processes to empower staff and
      increase quality of care. An Italian case study.
AB  - The rapid evolution of healthcare and the need to contain costs, to decrease the
      time of patients' hospitalization, and to improve the quality of care has led the
      nursing profession to face new challenges. This paper describes the case study of
      A.O. Ospedale Niguarda in Milan (Italy), a public healthcare provider where the
      key role of Nursing is being recognized according to international common
      practice. Also considering the context of Italian healthcare, attention will be
      drawn to concrete actions carried out on the organizational side and also for
      what concerns IT tools supporting nursing activities. This was done aiming with
      success at rising nurses' knowledge level of the patient, support its activities,
      increase quality of care, in a precise managerial and methodological framework.
      We will describe four cases of projects (Intensive Care Unit patient record,
      First Aid Station care reporting, pressure ulcers management, transfusion
      traceability) carried out by Niguarda with the support of its partner Fondazione
      Politecnico di Milano, set up to support bedside nursing activities with the most
      suitable technology for the purpose.

PMID- 19592822
TI  - Applying human factors analysis to the design of the electronic health record.
AB  - The healthcare industry is automating clinical documentation at the point of care
      - taking us from paper documentation to an electronic health record (EHR).
      Designing user-friendly, intuitive systems is challenging, and has motivated
      hospitals to evaluate and adopt new and safer practices to help reduce the
      contribution that technology plays in healthcare error. To accomplish this,
      healthcare is evaluating how other industries, like aviation, have successfully
      applied human factors to system design. Recent healthcare research has
      demonstrated the potential value of human factors in information technology (IT)
      projects. This article provides a synthesis of research on the application of
      human factors to the design and development of the electronic health record and
      makes apparent the need for human factors education for nurses and IT
      professionals involved in EHR design.

PMID- 19592823
TI  - HeartCareII: patients' use of a home care web resource.
AB  - In a six-month randomized field experiment our team evaluated the impact of a
      technology-enhanced practice (TEP) model compared to the usual care delivered by
      home care nurses. Research staff provided computers and technical assistance;
      home care visit nurses trained patients in the use of the components of the
      HeartCareII website most relevant to their care needs. The purpose of this paper
      is to explore participant exposure to the web-based HeartCareII resources, the
      technical core of the TEP. To assess exposure to the HeartCareII resources we
      counted logins, the number of accesses to the system, over each participant's
      study period. We determined that more logins occurred during the first four weeks
      of the participants' time in the study, with 50 percent continuing to logon after
      4 weeks. The number of participants accessing the system declined during the
      ensuing weeks to approximately one-third at eight weeks; almost 15 percent
      consistently logged in throughout their 24-week course in the experiment. This
      pattern of exposure to such web-based resources is consistent with findings of
      prior studies; it may support an episodic need for health resources in the home
      based on changing health demands.

PMID- 19592824
TI  - Alternative futures of proactive tools for a citizen's own wellbeing.
AB  - The aim of this paper is to create the basis for a vision of an empowered citizen
      who can control his/her life, especially in relation to health and personal
      wellbeing with the use of new ICT-tools. The methods used in the study are based
      on futures studies, especially on scenario methodology. Alternative future paths,
      i.e. scenarios are constructed using the scenario filter model that we have
      developed, with market, technology and society perspectives. Scenarios not
      resulting in the vision are described in what if - analysis as well. The
      scenarios are combined with Vihera's model on citizen's skills, access and
      motivation to use new ICT-tools. The concept COPER is targeted to different user
      groups with an adaptable user interface and its development is user centered. We
      will consider the effects and the appropriate elements of COPER in every
      scenario, as well as the possibilities and challenges nursing will confront. As a
      result we will gain information of the characteristic of COPER that advance the
      vision. For the future development of COPER the alternative scenarios give the
      basis for flexibility planning, too.

PMID- 19592825
TI  - Cancer patients' questions and concerns expressed in an online nurse-delivered
      mail service: preliminary results.
AB  - Internet-based online patient-nurse communication (OPNC) services can constitute
      an important opportunity to support patients to manage their illness between
      treatment and rehabilitation while being at home. We explored the content of
      messages sent by prostate and breast cancer patients to an OPNC service to
      identify symptoms, problems, concerns and information needs expressed in these
      messages. Using qualitative content analyses we examined 276 messages sent from
      38 breast and 22 prostate cancer patients during 15 months. Two main themes
      emerged: Concerns about physical symptoms and treatment side effects; and worries
      and questions about treatment and follow up. Analyses showed that cancer patients
      have many serious unanswered questions and concerns that can create considerable
      uncertainty and anxiety. An OPNC service can to a great extent meet patients'
      need for advice and information and thus be an important health care supplement
      that can improve quality of care.

PMID- 19592826
TI  - A text messaging trial in family planning clinics.
AB  - The New Zealand Family Planning Association (Family Planning) is a national not
      for-profit organization providing sexual and reproductive primary care health
      services as well as health promotion, professional training and advocacy on
      issues of sexual and reproductive health. By 2006 Family Planning had become
      acutely aware of the increasing amount of staff time being used to make phone
      calls to clients, particularly about appointment reminders and laboratory
      results, and the associated escalation in telephone costs. Much of the increased
      cost related to the trend for the clients, who are predominantly under 25 year of
      age, to have only a mobile phone as their phone contact. This paper describes a
      project to identify and implement an alternative means of communication with
      these clients, with the outcome being the introduction of a text messaging
      program (txt2remind) integrated with the Practice Management System (Medtech 32)
      into clinics by June 2008.

PMID- 19592827
TI  - Patient portals: survey of nursing informaticists.
AB  - As the US moves toward a more patient centered health care system, an integrated
      Electronic Health Record with a Patient Portal is one way that providers and
      patients can more actively collaborate in the health care process. A patient
      portal is an Internet-based interactive website for patients to communicate with
      their healthcare provider and with varied functions that gives them access to
      portions of their medical record and other services [1,2,3,4]. Many hospitals and
      health centers in the USA have developed patient portals while others are still
      in the planning stage. From a review of the literature it is evident that there
      is no standard of the scope of functions that are essential in the Patient
      Portals and to date most are only accessible in English. If we are truly moving
      towards a patient centered focus in health care in a diverse society, we need to
      design patient portals that tailor these resources to the needs of this diverse
      population. This paper reports on the results of an online survey that was
      distributed between August and October 2007 to nursing informaticists who
      subscribe to the CARING e-mail list and nursing informaticists working in the
      Greater New York City area. The goal of the survey was to see how many of the
      institutions where nursing informaticists work had patient portals, what
      functions were embedded in these portals, what research was being conduct., and
      what plans each institution had for future directions.

PMID- 19592828
TI  - The elderly demographic time bomb - sharing the load with the active ageing: can
      eHealth technologies help defuse it?
AB  - This paper examines strategic health management and practical health service
      delivery issues inherent in the potential doubling in the number of over 65s over
      the next two decades. It considers the use of scarce and overloaded resources in
      providing care and support to this age group across the spectrum of community
      environments, and advocates the use of shared information services coupled with
      the deployment of 'smart' technologies to supplement available yet scarce
      professional resources as well as enabling elderly people to maintain a safe,
      active and independent lifestyle. An innovative approach to provide support both
      to an active ageing population, as well as the more frail or vulnerable members
      of society, is outlined. Based on an ongoing research programme, this centres on
      the extension of the Smart Home concept to create an overarching smart
      environment. This combines advanced information, communications and textile
      technologies with physiological monitoring and location based processes and
      services, to protect and support users by maintaining the range of services they
      need. Discussion of the behavioural dynamics inherent in organizational change
      concludes the paper.

PMID- 19592829
TI  - The utilization of electronic patient record in pain management from the
      perspective of nursing management.
AB  - The electronic patient record is becoming more common in Finland. Structured and
      classified documentation methods make it possible to utilize different reports
      from EPR in the nursing management. OBJECTIVES: To describe how the knowledge of
      pain management in the EPR can be utilized in nursing management. METHODS: The
      descriptive data were collected from electronic patient records of patients with
      joint replacement in May 2008. RESULTS: There were 30 notes in the intensity
      measurement/assessments of pain versus 1788 in the pain control. DISCUSSION: The
      patient records show shortage in nursing documentation. This paper does not show
      the reason and therefore further research is needed. However this makes the
      nursing manager act.

PMID- 19592830
TI  - Patients reading their health records - what emotional factors are involved?
AB  - In many countries, an increasing number of patients now make use of their legal
      right to access their health record. In this paper we shed light on the role of
      emotional factors involved when patients read their record. We report the
      preliminary results from an interview study in which eight patients who have
      asked for a copy of their electronic health record following a hospital stay have
      been interviewed. Our results show that distrust is an important emotional factor
      involved in asking for record access. When reading the record, several patients
      also discovered discrepancies between verbal communication and the written
      documentation, which causes irritation and resentment. Patients' reactions were
      due to health personnel's lack of openness in direct communication with them. We
      conclude that health personnel should be prepared to go more into the role as
      discussion partners with patients to show that their concerns are taken
      seriously, and that more should be done to avoid documentation errors due to
      weaknesses in documentation routines.

PMID- 19592831
TI  - Integration of self-management tools in personal and provider e-health records.
AB  - Development and evaluation of research-quality informatics tools for self
      management support in personal and provider electronic health records (PHRs and
      EHRs) may improve patient outcomes by facilitating patient and provider education
      and communication around goal-setting, prompting consistent evidence-based
      treatment, and providing reminders and feedback. Nurses on primary care teams are
      well-positioned to advocate for self-management and monitor the use of these
      informatics tools. This paper presents a design for integrating goal-setting
      tools into PHRs and EHRs. Keeping in mind the potential of enhanced self
      management support, challenges in basic issues such as user characteristics,
      practice traditions of data ownership and workflow, and financing are discussed.

PMID- 19592832
TI  - Reading between the numbers: the potential of patient narrative.
AB  - The prevalence of online sharing of an illness experience suggests that some
      patients find real value in narrative. Set in the presence of evolving personal
      health records, a new venue for the therapeutic relationship is emerging,
      creating an opportune moment for nursing to influence the structure of this new
      model of care.

PMID- 19592833
TI  - Evaluating pain in intensive care.
AB  - Optimal pain management is essential for good care outcomes, but assessing pain
      is particularly complex in intensive care, as patients are often unable to
      communicate. We hypothesize that the task could be supported through human
      language technology. To evaluate the feasibility of such tools, we study how pain
      is documented in electronic Finnish free-text intensive care nursing notes by
      statistically comparing annotations of ten nursing professionals on a set of 1548
      documents. The aspects considered include the amount and writing style of pain
      related notes, pain intensity, and given pain care. More than half of the
      documents contained information relevant for patients' pain status but it was
      expressed usually indirectly. Also pain medication was commented as free-text.
      Although annotators' pain intensity evaluations diverged, the substantial amount
      of pain-related notes encourages developing computational tools for pain
      assessment.

PMID- 19592834
TI  - Challenges of electronic medical record extracts for a personal health record.
AB  - The goal of providing electronic medical record (EMR) extracts is to facilitate
      patient participation in their healthcare and enhance patient-provider
      collaboration. There are many challenges in selecting a subset of the information
      available in an electronic medical record (EMR) for export to a Web-based
      personal health record (PHR). Critical success factors include perspectives in
      decision-making about what information to extract and assumptions about how
      extracted information will be used. Existing hard copy release of electronic
      medical record information provides a starting point. Guiding principles for the
      extract selection process include extracting information with meaning for the
      patient, user-friendly presentation of that information, and identifying how the
      patient will learn more about the information presented. Since a patient may
      choose to share their extract, a context is necessary in order for a healthcare
      team member to make sense of the extracted information. Part of the extract
      selection process is identifying patient education, clinical adoption, and
      evaluation strategies. Models and frameworks to guide evaluation are essential
      for success.

PMID- 19592835
TI  - Telenursing in primary health care: report of experience in southern Brazil.
AB  - The Rio Grande do Sul Telematics and Telehealth kernel in Brazil, aims to enhance
      the quality of the Unified Health System (UHS) in support of primary health care
      (PHC) services, most of them engaged in the Family Health Program (FHP). Among
      the initiatives of the TeleHealth Rio Grande do Sul, there is consulting via e
      mail and videoconference. They are requested and answered using specific forms
      available on TeleHealth's intranet. This study registers the experience on
      supporting and answering demands using clinical evidence, and presents
      professional characteristics and some results reached until now. Data related to
      professional characteristics were extracted from a questionnaire prepared by the
      program execution team, and applied during training sessions in 2007 and 2008.
      Consults sent by nurses, technicians and community health agents were analyzed
      considering its number and content. The analyzed sample of nurses showed that
      89.1% were female, 40% younger than 30 years old and the majority graduated
      within the past 5 years. Most of them (97) work for the FHP and 51.61% have a pos
      graduate degree. Most of the interviewed nurses use e-mail to communicate and the
      internet at least once a week. So far, the program TeleHealth Rio Grande do Sul
      have received 498 consult requests, 111 related to the nursing field. The nurses
      answer nursing related doubts, sent by nursing technicians and community health
      agents. The consults involve several different subjects, mainly on wounds, woman
      health, drugs and medicines. Considering the consults demanded, the group decided
      to create health care protocols, starting with the most requested subjects, such
      as the wounds, which is about to be released on the Rio Grande do Sul TeleHealth
      website.

PMID- 19592836
TI  - Building knowledge for poison control: the novel pairing of communication
      analysis with data mining methods.
AB  - As information systems become increasingly integrated with health care delivery,
      vast amounts of clinical data are stored. Knowledge discovery and data mining
      methods are potentially powerful for the induction of knowledge models from this
      data relevant to nursing outcomes. However, an important barrier to the
      widespread application of these methods for induction of nursing knowledge models
      is that important concepts relevant to nursing outcomes are often unrepresented
      in clinical data. For instance, communication approaches are not necessarily
      consciously chosen by nurses, yet they are known to impact multiple clinical
      outcomes including satisfaction, pain and symptom response, recovery,
      physiological change (e.g., blood pressure), and adherence. Decisions about
      communication behaviors are likely intuitive and instantaneously made in response
      to cues offered by the patient. For this reason, among others, important choices
      and actions of nurses are not routinely documented. And so for many clinical
      outcomes relevant to nursing, important concepts such as communication are not
      represented in clinical data repositories. In studying poison control center
      outcomes, it is important to consider not only routinely documented clinical
      data, but the communication processes and verbal cues of both patient and SPI. In
      a novel approach, our current study of poison control center outcomes pairs a
      qualitative study of the communication patterns of SPIs and callers to a regional
      poison control center, with predictive modeling of poison control center outcomes
      using knowledge discovery and data mining methods. This three year study,
      currently in progress, pairs SPI-caller communication analysis with predictive
      models resulting from the application of knowledge discovery and data mining
      methods to three years' of archived clinical data. The results will form a hybrid
      model and the basis for future decision support interventions that leverage
      knowledge about both implicit and explicit factors that contribute to poison
      control center outcomes.

PMID- 19592837
TI  - Project HealthDesign: enhancing action through information.
AB  - Project HealthDesign is a country-wide initiative in the United States designed
      to stimulate innovation in personal health records (PHRs). Nine grantee teams
      engaged in an 18-month long design and prototyping process. Two teams addressed
      the needs of children and adolescents; three created novel approaches to help
      adults prevent or manage metabolic syndrome; three groups employed interface
      innovations to assist patients with chronic care management and one team devised
      a novel calendaring system to assist patients undergoing complex medical/surgical
      treatments to integrate care processes into their daily lives. These projects not
      only included development and testing of novel personal health records
      applications, but also served as the starting point to specify and implement a
      common technical core platform. The project advanced PHR development in two key
      ways: intensive user-centered design and a development architecture that
      separates applications of PHRs from the infrastructure that supports them. The
      initiative also allowed systematic investigation of significant ethical, legal
      and social issues, including how privacy considerations are changed when
      information technology innovations are used in the home and the rebalancing of
      the authority structure of health care decision making when patient-centered
      approaches guide the design of PHRs.

PMID- 19592838
TI  - User requirements for a practice-integrated nurse-administered online
      communication service for cancer patients.
AB  - This paper describes the use of participatory design methods in the development
      of a nurse-administered online patient-provider communication (OPPC) service that
      is designed to be integrated into routine clinical practice. The OPPC service let
      patients stay connected with expert nurses and other health care providers to ask
      questions and receive advice from home. Through focus groups, workshops,
      heuristic evaluations and usability testing, we identified patients' and
      clinicians' (nurses' and physicians') user requirements, factors important for
      successful adoption, implementation and maintenance of the OPPC service, and
      usability. This paper shares important insights from these participatory design
      processes that may be helpful for other researchers who wish to implement
      clinical applications into routine practice.

PMID- 19592839
TI  - Experiences with the electronic nursing discharge summary.
AB  - The aim of this paper is to describe nursing staff's experiences with the
      Electronic Nursing Discharge Summary (ENDS) [Hoitotyon yhteenveto, HOIY]. This
      study is a part of the Salpa project of the Satakunta Hospital District (SHD).
      The goal of the project was to implement the Regional Information System (Fiale
      System) for social and health care in Satakunta, Finland. During the project
      (2004-2007), 3600 social and health care professionals were trained to use the
      Fiale System. The ENDS is used in the patient transfer phase. It complies with
      the national definition work of core information and can be opened through the
      Fiale System. The ENDS includes basic information on the care period in question
      for purposes of further care. 22 nurses, both those processing and those
      receiving the ENDS were interviewed by phone in 2006 about their experiences and
      satisfaction with the ENDS. The data was analyzed using content analysis.
      Experiences with this system are mainly positive. When done carefully, the ENDS
      enables real time communication, fast enough and safely, though the new structure
      needs consideration and documentation takes time. On the basis of this and other
      studies it can be concluded that acceptance of the nursing documentation process
      is more important than IT skills [1]. The ENDS has a guiding role as a tool for
      supporting nurses in their day-to-day documentation.

PMID- 19592840
TI  - The role of IT in facilitating the centralised co-ordination of agency and bank
      nursing within an acute hospital.
AB  - Healthcare organisations have to operate within finite resources. It is widely
      acknowledged that supplementary agency and bank nurses are needed to fill vacant
      hospital shifts that cannot be filled by permanent staff. In Ireland a project
      was initiated in the main Dublin Academic Teaching Hospitals, to centralise the
      coordination of all Bank and Agency activity within each individual institution.
      This paper outlines the necessity for such a move, and describes the steps one
      hospital has taken in developing and implementing an electronic Nursing Bank
      Management System.

PMID- 19592841
TI  - A study of best practices for clinical documentation system implementation.
AB  - Nurses are key leaders and team members for the implementation of clinical
      documentation systems. This paper reviews key success factors during
      implementation of clinical documentation systems to overcome traditional
      barriers, ensure commitment to universal goals and facilitate the use of
      technology for patient safety and continuous quality improvement efforts. Top
      level management support, particularly from nursing executives, is vital.

PMID- 19592842
TI  - Implementation of a regional health information system - overview of selected
      outcomes in one hospital district.
AB  - The aim of this paper is to give an overview of some selected outcomes after the
      implementation of a Regional Health Information System (RHIS) in one hospital
      district in Finland. The implementation project of the Regional Health
      Information Systems (SALPA) administered by Satakunta Hospital District in 2004 -
      2007 is comprised of integrated services between primary, secondary and tertiary
      care. The general aim was to provide the member municipalities' access to
      specialised health care information and sustain seamless care, and to enhance
      organisational information exchange regardless of time and place. The data were
      collected by using computer-based statistics and reports in 2004 - 2007 of the
      selected outcomes: laboratory and radiology tests and appointments in the member
      municipalities of the hospital district area. Preliminary results of the selected
      outcomes indicate that the laboratory tests seem mainly to have increased.
      However, the radiographic tests and the clinicians' appointments seem mainly to
      have reduced. A deeper investigation should be done in order to determine the
      outcomes in the field under investigation.

PMID- 19592844
TI  - The evaluation of using road-map guided Excel VBA training to promote nursing
      informatics in Taiwan.
AB  - In Taiwan nursing informatics is taking off. It is therefore strategically
      important to educate our nurses what nursing informatics is in a short time. We
      used a method of road-map guided Excel VBA to educate our nurses how to cope with
      their informatics needs. An eight-day training program based on this concept was
      implemented in the one regional hospital and a survey was done at the end of the
      program to evaluate the participants' perception of the training program. The
      results show very high acceptance and positive outcomes. We suggest that the
      method of road-map guided Excel VBA might be a promising strategy to promote
      nursing informatics internationally Taiwan.

PMID- 19592843
TI  - Barriers to implementation of a Continuity of Care Record (CCR) in HIV/AIDS care.
AB  - This qualitative study was part of the pre-implementation formative evaluation of
      SelectHealth's Continuity of Care Record (CCR), an electronic health information
      network (EHI) for HIV/AIDS care in New York City (NYC). The purpose of the study
      was to explore case managers' perceptions of the barriers to adoption of the CCR.
      Focus group methodology was used to gather perceptions from 26 participants who
      provided direct case management services for persons living with HIV/AIDS (PLWHA)
      in NYC. Question development was guided by models of technology acceptance. Data
      about the barriers to implementation of the system were classified into four main
      themes: client capacity for system adoption, potential breech of confidentiality,
      information quality concerns, and training needs. The four identified themes can
      serve as focal points for developers seeking to create EHI networks for the
      provision of HIV care.

PMID- 19592845
TI  - Sociotechnical analysis of a neonatal ICU.
AB  - Sociotechnical theory has been used to inform the development of computer systems
      in the complex and dynamic environment of healthcare. The key components of the
      sociotechnical system are the workers, their practices, their mental models,
      their interactions, and the tools used in the work process. We conducted a
      sociotechnical analysis of a neonatal intensive care unit towards the development
      of decision support for antimicrobial prescribing. We found that the core task
      was to save the baby in the face of complex and often incomplete information.
      Organizational climate characteristics were pride in clinical and educational
      practice. In addition, the structure of work identified interdisciplinary
      teamwork with some communication breakdown and interruptive work environment.
      Overall, sociotechnical analysis provided a solid method to understand work
      environment during the decision support development process.

PMID- 19592846
TI  - Implementation of an enterprise-wide Electronic Health Record: a nurse-physician
      partnership.
AB  - Maimonides Medical Center (MMC), a 705-bed tertiary hospital located in Brooklyn,
      New York, is a not-for-profit, voluntary hospital and the third largest
      independent teaching hospital in the United States. Its strategic plan includes
      research and academic initiatives, specifically, physician and nursing leadership
      development and a nursing scholarship program. In 1996 executive management
      allocated resources for the development of an information technology environment
      to improve the quality of care, increase patient satisfaction, reduce costs, and
      position the hospital for future growth initiatives, all accomplished through the
      use of an Electronic Health Record (EHR). The result was the Maimonides Access
      Clinical System (MACS) that has transformed the delivery of health care
      throughout MMC and serves as a model for other US hospitals. In addition, since
      2007, MMC has also participated in the Brooklyn Health Information Exchange
      (BHIX) a New York State HEAL grant initiative implementing a Regional Health
      Information Organization (RHIO), an exchange of clinical information between
      Brooklyn hospitals, nursing homes, and home health agencies that aids in the
      transition of care for its shared patients.

PMID- 19592847
TI  - Sending electronic nursing discharge messages using the HL7 v3 Care Provision
      standard.
AB  - There is a growing need to exchange nursing related information electronically
      from one health care professional to another, crossing institutional, time and
      language boarders. Both continuity of care, care for populations, decision
      support and secondary use of patient data are valid uses of nursing information.
      Achieving electronic exchange of nursing information requires information
      analysis, modeling, standardization and deployment in electronic health systems.
      The HL7 working group 'Patient Care' has developed a set of HL7 v3 messages that
      allows nursing content to be specified and exchanged between electronic patient
      record systems, or systems deployed for secondary data use. This contribution
      discusses the dynamics of the process and the use of electronic messages for
      continuity of care. Also, the use of nursing terminology and assessment scales
      within HL7 v3 messages is illustrated. The Care Provision message is useful for
      sending structured nursing information between health care facilities.

PMID- 19592848
TI  - Four-level process modeling in healthcare SOA analysis and design.
AB  - Process and activity modeling are widely used in healthcare work and systems
      development projects. There are various approaches and abstractions available for
      process modeling. This study describes a four-level approach to activity and
      process modeling which has been used in modeling healthcare activities in
      relation to the specification of service-oriented information systems solutions.
      Based on the material and experience from these efforts: 1) overview level
      descriptions are well capable of illustrating the domain of the development, 2)
      many current notations and techniques on process level fail to describe diverse
      practices in healthcare, 3) descriptions on activity level should be generalized
      and combined in novel ways to achieve reuse and to support complex domains, 4)
      very accurate and detailed action-level modeling should be used cautiously to
      reduce unnecessary workload and to focus on the essential features of the
      solutions.

PMID- 19592849
TI  - Using ruby on rails to develop a web interface: a research-based exemplar with a
      computerized physical activity reporter.
AB  - The world is becoming increasingly web-based. Health care institutions are
      utilizing the web for personal health records, surveillance, communication, and
      education; health care researchers are finding value in using the web for
      research subject recruitment, data collection, and follow-up. Programming
      languages, such as Java, require knowledge and experience usually found only in
      software engineers and consultants. The purpose of this paper is to demonstrate
      Ruby on Rails as a feasible alternative for programming questionnaires for use on
      the web. Ruby on Rails was specifically designed for the development, deployment,
      and maintenance of database-backed web applications. It is flexible,
      customizable, and easy to learn. With a relatively little initial training, a
      novice programmer can create a robust web application in a small amount of time,
      without the need of a software consultant. The translation of the Children's
      Computerized Physical Activity Reporter (C-CPAR) from a local installation in
      Microsoft Access to a web-based format utilizing Ruby on Rails is given as an
      example.

PMID- 19592851
TI  - E-documentation as a process management tool for nursing care in hospitals.
AB  - Appropriate documentation plays a key role in process management in nursing care.
      It includes holistic data management based on patient's data along the clinical
      path with regard to nursing care. We developed an e-documentation model that
      follows the process method of work in nursing care. It assesses the patient's
      status on the basis of Henderson's theoretical model of 14 basic living
      activities and is aligned with internationally recognized nursing
      classifications. E-documentation development requires reengineering of existing
      documentation and facilitates process reengineering. A prototype solution of an e
      nursing documentation, already being in testing process at University medical
      centres in Ljubljana and Maribor, will be described.

PMID- 19592850
TI  - The development of a quality-and-multimedia-based health web information
      searching tool.
AB  - People have not been satisfied with the search tools of web health information.
      We built a prototype easy-to-use web information searching tool by using
      multimedia techniques, combined with the emphasis of result presentation and
      content quality information. Instead of traditional search methods, we provide
      quality and webpage source information of websites for people to get useful
      information, and present search result by graphs and animations for people to get
      better user experience.

PMID- 19592852
TI  - Development of a measurement instrument for nursing documentation in the patient
      record.
AB  - OBJECTIVES: To develop, validate and test the reliability of a measurement
      instrument that measures the extent to which records describe essential aspects
      of nursing care such as the admission report, nursing diagnoses, interventions,
      and progress and outcome evaluations. METHOD: A measurement instrument was
      developed based on the Cat-ch-Ing instrument and the Scale for Degrees of
      Accuracy in Nursing Diagnoses. A record screening was conducted in 7 hospitals in
      the Netherlands. Content validity was tested by using two Delphi panels. Each of
      the 250 records was assessed by two reviewers independently. The reliability of
      the instrument was tested by calculating Cohen's weighted Kappa inter-rater
      reliability coefficient of 250 records and 12 reviewers. Internal consistency was
      calculated by using Cronbach's alpha. RESULTS: The new measurement instrument,
      named D-Catch, consists of six items. Quantity and quality variables were used to
      judge the accuracy of the nursing documentation. Internal consistency: Cronbach's
      Alpha 0.722. The inter-rater reliability coefficients were between 0.397-1.000.
      CONCLUSIONS AND IMPLICATIONS: The D-Catch instrument was estimated to be a valid
      and reliable measurement instrument for nursing records in hospitals in the
      Netherlands. An adverse effect on the inter-rater reliability may have been that,
      specifically in long stay situations, documentation forms with diagnoses,
      interventions and outcomes were often unstructured and found to be repetitious.

PMID- 19592854
TI  - Evaluation of the content coverage of SNOMED-CT to represent ICNP Version 1
      catalogues.
AB  - To evaluate the ability of SNOMED-CT (Systematized Nomenclature of Medicine
      Clinical Terms) to represent ICNP (International Classification for Nursing
      Practice) nursing diagnosis and intervention catalogue concepts. We selected the
      194 nursing diagnosis and 139 nursing intervention catalogue statements from ICNP
      Version 1.0. From June 2007 through December 2007, the first author mapped the
      ICNP catalogue concepts to SNOMED-CT using Apelon's TermWorks and CLUE browser
      5.0. The second and fourth authors from SNOMED Terminology Solutions and the
      third author from ICN validated the mapping result. SNOMED-CT covered 172
      concepts of 194 nursing diagnosis and 136 concepts of 139 nursing intervention
      catalogue concepts. SNOMED-CT can represent most (92.5%) of the ICNP nursing
      diagnosis and intervention catalogue concepts. Improvements to synonymy and
      adding missing concepts would lead to greater coverage of nursing diagnosis and
      intervention catalogue concepts.

PMID- 19592855
TI  - Towards a standardized representation to support data reuse: representing the
      ICNP semantics using the HL7 RIM.
AB  - Representing nursing assessment data in a reusable manner is important as it
      provides a basis for decision making in patient care. In a previous study, we
      have extended the ICNP concept model to support representation of nursing
      assessment data. In this study, we evaluated its potential to support electronic
      documentation of nursing assessment data and HL7 conformant message generation by
      mapping it to the HL7 RIM. The semantics represented by the ICNP were completely
      related to the RIM implying that the ICNP is a good candidate terminology to
      encode the data with in an electronic documentation system. A few differences
      between the two models in representing the same semantics suggests that there is
      value to supporting broad ranges of semantic relations in the ICNP.

PMID- 19592856
TI  - Representation of patients' health asset concepts in the International
      Classification of Nursing Practice (ICNP).
AB  - The purpose of this study was to evaluate the representation of health asset
      concepts in the International Classification of Nursing Practice (ICNP). In a
      previous study we conducted a concept analysis of health assets, building a
      conceptual model. The terms included in our conceptual model were cross-mapped to
      the ICNP terminology system, Version 1.0/1.1. Most of the health asset terms in
      the conceptual model were represented in ICNP. However, for maximum support of
      both clinical nursing care and patient self-care, a complete set of health asset
      terms is needed in the ICNP. We advocate for more research to uncover patients'
      and clinicians' detailed use of health asset terms. This should result in a
      richer and more specific health assets vocabulary that could be integrated into
      ICNP or other nursing terminologies as a means to improve nursing care and to
      strengthen patients' self-management of their illnesses. However, the findings
      from this first evaluation of health asset terms in the ICNP are promising, at
      least on a global level.

PMID- 19592857
TI  - The ICNP BaT - from translation tool to translation web service.
AB  - The ICNP BaT has been developed as a web application to support the collaborative
      translation of different versions of the ICNP into different languages. A
      prototype of a web service is described that could reuse the translations in the
      database of the ICNP BaT to provide automatic translations of nursing content
      based on the ICNP terminology globally. The translation web service is based on a
      service-oriented architecture making it easy to interoperate with different
      applications. Such a global translation server would free individual institutions
      from the maintenance costs of realizing their own translation services.

PMID- 19592859
TI  - Models, standards and structures of nursing documentation in European countries.
AB  - The use of standardized nursing languages varies between and even within
      different European countries. Standardization of a nursing language is a
      demanding process which requires substantial methodological and technological
      knowledge as well as cultural experience in terminology development work. A
      survey was carried out to describe the current state of art of the use of models,
      standards and structures in nursing documentation. A web-based questionnaire was
      targeted to members of the Association for Common European Nursing Diagnoses,
      Interventions and Outcomes (ACENDIO). Replies were received from 17 countries in
      Europe. Results show that the nursing process is the model most often used to
      structure nursing documentation in Europe. Many standardized nursing
      terminologies are used in Europe but general use in nursing is still lacking
      which makes access to nursing data an obstacle. In more than 60% of the
      institutions in the countries that replied were nursing data not stored and could
      therefore not be retrieved. These results should be a major concern to nurses in
      Europe. This relates to the lack of use of standards in use of nursing
      terminologies and information systems. Standardization activities in existing and
      evolving networks in Europe, as well as in other parts of the world, need to be
      enhanced. As a European platform, ACENDIO can play a role in these
      standardization activities and should develop its role accordingly.

PMID- 19592860
TI  - Effects of terminology based documentation on nursing.
AB  - The aim of this literature review was to discover what the effects are of the
      standardized nursing documentation. The material used for conducting was drawn
      from CINAHL, PubMed and Cochrane databases. The search was confined to relevant
      electronically retrievable studies with links to full text and published in the
      English language in 2007-2008. These criteria yielded 19 studies. The results
      indicate that there are mainly positive effects when using nursing terminologies
      in documenting patient care.

PMID- 19592861
TI  - Preparing nurses to use standardized nursing language in the electronic health
      record.
AB  - Research demonstrated nurses' education needs to be able to document nursing
      diagnoses, interventions and patient outcomes in the EHR. The aim of this study
      is to investigate the effect of Guided Clinical Reasoning, a learning method to
      foster nurses' abilities in using standardized language. In a cluster randomized
      experimental study, nurses from 3 wards received Guided Clinical Reasoning (GCR),
      a learning method to foster nurses in stating nursing diagnoses, related
      interventions and outcomes. Three wards, receiving Classic Case Discussions,
      functioned as control group. The learning effect was measured by assessing the
      quality of 225 nursing documentations by applying 18 Likert-type items with a 0-4
      scale of the measurement instrument "Quality of Nursing Diagnoses, Interventions
      and Outcomes" (Q-DIO). T-tests were applied to analyze pre-post intervention
      scores. GCR led to significantly higher quality of nursing diagnosis
      documentation; to etiology-specific nursing interventions and to enhanced nursing
      sensitive patient outcomes. Before GCR, the pre-intervention mean in quality of
      nursing documentation was = 2.69 (post-intervention = 3.70; p<.0001). Similar
      results were found for nursing interventions and outcomes. In the control group,
      the quality remained unchanged. GCR supported nurses' abilities to state accurate
      nursing diagnoses, to select effective nursing interventions and to reach
      enhanced patient outcomes. Nursing diagnoses (NANDA-I) with related interventions
      and patient outcomes provide a knowledgebase for nurses to use standardized
      language in the EHR.

PMID- 19592862
TI  - The use of nursing terminology in electronic documentation.
AB  - The purpose of this study is to describe the use of nursing terminology in
      nursing documentation in the neurological care setting. The use of standardized
      terminology in nursing documentation allows the visualization of nursing practice
      and makes it quantifiable. Once collected, data can also be reused for
      administrative purposes. In Finland the Nursing Minimum Data Set (NMDS) is part
      of the core data set of patient electronic health records. The Nursing Minimum
      Data Set has been complied using the Finnish Classification of Nursing
      Interventions (FiCNI) and Finnish Classification of Nursing Diagnoses (FiCND),
      both based on the Clinical Care Classification. Standardized terminology was
      introduced in nursing documentation in 2004. The data form part of a wider set of
      electronic health record data (2003-2006). The data consist of 40 neurological
      nursing care plans. The data were analysed using statistical methods and content
      analysis. Nursing terminology had been widely used in nursing documentation.
      However, there remains a clear need for both training in and further validation
      of the terminology currently used.

PMID- 19592863
TI  - Formalizing nursing knowledge: from theories and models to ontologies.
AB  - Knowledge representation in nursing is poised to address the depth of nursing
      knowledge about the specific phenomena of importance to nursing. Nursing theories
      and models may provide a starting point for making this knowledge explicit in
      representations. We combined knowledge building methods from nursing and ontology
      design methods from biomedical informatics to create a nursing representation of
      family health history. Our experience provides an example of how knowledge
      representations may be created to facilitate electronic support for nursing
      practice and knowledge development.

PMID- 19592864
TI  - Developing a taxonomy and an ontology of nurses' patient clinical summaries.
AB  - Nurses prepare a summary of patient information that they consult and update
      throughout the shift. This document is believed to be integral to cognition,
      working memory, and decision-making. While serving as a key support to nursing
      practice, this summary also represents risks to patient safety. Characterized as
      a PCCAT, or Personally Created Cognitive Artifact, studies of this document in
      the context of nursing practice have not been reported. The absence of reported
      research, the importance of the document to nurse cognition and practice, and
      related safety risks prompted the research that this paper discusses. A taxonomy
      was developed through the analysis and coding of 151 PCCATs. Further analysis and
      mapping provided an ontology of the PCCAT. Content differences were noted between
      nursing units and among nurses. This may reflect differences in unit-based
      culture and/or differences in the patient complexity. The interaction between
      culture and perceived complexity of practice is one of the great difficulties in
      generating automated information systems for clinical practice settings. This
      paper is part of a larger research protocol that explores meta-level knowledge
      structures and revision to the understanding of the granularity of nursing
      knowledge. Development of a taxonomy and ontology of the nurse PCCAT, an
      important component of the larger research protocol, is described in this paper.

PMID- 19592865
TI  - Intensive care admission and discharge - critical decision-making points.
AB  - Delivery of intensive care has many critical points impacting the outcomes of
      critically ill patients. Two important key events in intensive care are patients'
      admission and discharge procedures. The decision making of intensive care experts
      should be supported in these two points, in order to attain good quality and safe
      care. We hypothesize that in the future this decision-making process can be
      effectively supported with information technology. To reveal the complex decision
      making, we studied the decision-making processes and information needs of
      intensive care charge nurses during patients' admission and discharge procedures.
      We identified several interconnected decision-making steps during these
      procedures.

PMID- 19592866
TI  - Interdisciplinary communication in the ICU.
AB  - Interdisciplinary communication in the Intensive Care Unit (ICU) is complicated
      by the dynamic workflow of clinicians, instability of patients, and highly
      technological therapies, equipment and information systems. Many countries have
      examined methods to improve clinician communication and to understand common
      patient care goals. Using focus group and interview transcripts of ICU nurse
      practitioners, medical residents, medical fellows and attending physicians about
      antibiotic prescribing, we performed a secondary analysis of themes related to
      interdisciplinary communication with registered nurses (RNs). This qualitative
      descriptive user analysis utilized Baggs and Schmitt's Interdisciplinary
      Collaboration Model as a coding framework. We found that the clinicians studied
      value the availability of time sensitive information when it impacts their
      decisions and workflow and trust RNs' judgment of clinical information and
      situations. Future work should include analyses of RN perceptions of
      interdisciplinary communication in the ICU.

PMID- 19592867
TI  - Implementation of a structured nursing documentation in a special care unit.
AB  - The purpose of this article is to describe the piloting of nursing documentation
      in accordance with the national model in the Oulu University Hospital. The
      nursing documentation in Finland is based on the nursing process model and
      Nursing Minimum Data Set (NMDS). NMDS includes information on nursing
      diagnoses/needs; interventions, outcomes, patient care intensity and discharge
      summary. Nursing staff received education for documenting content which is
      consistent with the nursing process in the The Finnish Care Classification
      (FinCC). The new documentation model required time for all professional groups in
      the beginning. New documentation models is challenging, adequate time needs to be
      reserved for the staff in order to establish new documentation procedures.
      Successful implementation of the pilot necessitated the commitment of the nursing
      officers.

PMID- 19592869
TI  - Severity of illness - implications for information management by patients.
AB  - As more and more people are living with chronic diseases, there is a greater need
      for patients to have access to accurate and reliable information about health in
      general and their own health care in particular. In this study we explored how
      patients suffering from chronic heart insufficiency who needed post-hospital home
      nursing care assessed their need for health information and their use of the
      health information they received. Fourteen patients were interviewed in their
      homes one week after their discharge. Using a thematic approach, we identified
      three main areas: the hospital systems for providing information to patients, how
      patients processed the information, and how patients managed the information.
      Next of kin had a significant role in information management for the patient. The
      patient's condition has implications for his or her ability to manage the
      information, and therefore it seems important to customize information according
      to the patient's level of comprehension.

PMID- 19592870
TI  - Health information systems and improved patient outcomes: do nurses see the
      connection?
AB  - A major focus of nurses is to improve patient outcomes, and any introduction of
      technology into their work environment should add value through enhancing patient
      care and contributing to the development of nursing intelligence. This study
      addressed whether nurses working in an emergency department (ED) perceived a
      relationship between using an emergency department information system (EDIS) and
      patient outcomes. A cross-sectional survey design was used, with data collected
      from the population (n=168) of nurses from five Australian metropolitan public
      hospital emergency departments (EDs). The questionnaire collected information on
      how EDIS impacted on patient outcomes in terms of waiting times, triage process,
      departmental accountability, documentation focus, computer interaction, and
      system purpose. Nurses acknowledged the value of an information system in
      improving the triage process and increasing the accountability of the ED, however
      failed to identify any impact on reducing overall ED waiting times or its
      relationship to improved care delivery. Over half the respondents could not
      identify negative effects such as compelling nurses to focus on documentation
      details or 'treat the computer' rather than the patient. The use of technology in
      this study evoked optimistic responses, however results indicated a lack of
      clarity about the impact of EDIS on patient outcomes.

PMID- 19592871
TI  - Individualizing cancer care with interoperable information systems.
AB  - There are three levels of interoperable informatics that are co-occurring in the
      United States to link data to provide more comprehensive care to patients. One is
      the National Health Information Network (NHIN) that is establishing use case
      scenarios and standards for interoperability for patients with multiple
      conditions. The second is the National Cancer Institute's project that supports
      the enterprise work called the Cancer Bioinformatics Grid (caBIG) in linking
      clinical care with bioinformatics, tissue repositories, and imaging for patients
      with cancer. The third is in the area of translating the discoveries of biology
      to bedside care through the National Institutes of Health (NIH) translational
      research efforts to get these new biomedical and genomic discoveries in practice
      in multiple healthcare delivery environments. These developments are becoming
      global networks in the diagnosis and cure of cancer as the primary outcome. This
      paper describes the national efforts and the global connection to Europe through
      the caBIG program. The European program that is beginning to link to cancer
      research internationally is the National Cancer Research Institute (NCRI) in the
      United Kingdom. They are developing the NCRI Oncology Information Exchange (ONIX)
      to provide the cancer research community with the ability to share information.

PMID- 19592872
TI  - Structuring clinical nursing knowledge using PCAPS - patient condition adaptive
      path system.
AB  - Quality assurance has become key concerns in healthcare and it is important to
      standardize the processes for healthcare properly. Though it was needed to
      describe process of healthcare diagnosis and treatment, it was very difficult by
      the reason of being service products including complexity and expertise. We
      challenged to visible, structurize, standardize and IT-systematize of clinical
      knowledge for healthcare quality management. The patient condition adaptive path
      system (PCAPS) was developed. PCAPS describes an overall flow of possible
      clinical pathways that a patient's disease state may trace and detailed medical
      judgment and treatments for each disease state. It suggests possibility of
      quality assurance using the standard plan of medical treatment process. PCAPS
      comprises two major tools: clinical process chart and unit sheet. These describe
      the total flow of treatment and the concrete medical treatments involved in each
      step. The PCAPS master is proposed. This is a glossary of the terms that are used
      in the unit sheet. Each master file has special structure for each work domain.
      In other words, PCAPS describes the standard process of healthcare using the
      clinical process chart, unit sheet, and PCAPS master. We apply nursing master
      file for nursing care action and observation offered by MEDIS-DC in Japan.
      Through we developed many PCAPS contents, we identified description of structured
      nursing knowledge. The nursing master file was brushed up by designing PCAPS
      content using it. It was suggested that PCAPS contents as standard clinical plan
      designed by medical specialist team included nursing knowledge.

PMID- 19592873
TI  - Nurses attitudes towards the informed patient.
AB  - The widespread use of the Internet for health information has resulted in
      knowledgeable clients referred to as "informed patients". Many patients bring the
      information they downloaded from the Internet to the appointments with the health
      care workers. OBJECTIVES: The present study examined the prevalence of nurses'
      encounters and attitudes to these patients and factors that might influence
      attitudes. METHOD: A cross-sectional study of a convenience sample of 110 nurses
      in Israel was conducted. The main variables measured were: attitudes,
      professional self-esteem, and two indices of Internet use. RESULTS: The results
      show that most nurses held positive attitudes towards patients presenting
      Internet Medical Information. Nurses with prior experience had more positive
      attitudes than nurses with no such experience. Professional self-esteem and
      Internet use were also positively correlated to positive attitudes to these
      patients. CONCLUSIONS: Since patients search the Internet for medical
      information, there is a need to prepare and train nurses to be Internet literate
      in order to be prepared for encounters with such patients.

PMID- 19592874
TI  - The impact of Health Information Technology (I-HIT) Scale: the Australian
      results.
AB  - One of role of the nurse in the clinical setting is that of co-ordinating
      communication across the healthcare team. On a daily basis nurses interact with
      the person receiving care, their family members, and multiple care providers thus
      placing the nurse in the central position with access to a vast array of
      information on the person. Through this nurses have historically functioned as
      "information repositories". With the advent of Health Information Technology
      (HIT) tools there is a potential that HIT could impact interdisciplinary
      communication, practice efficiency and effectiveness, relationships and workflow
      in acute care settings [1][3]. In 2005, the HIMSS Nursing Informatics Community
      developed the I-HIT Scale to measure the impact of HIT on the nursing role and
      interdisciplinary communication in USA hospitals. In 2007, nursing informatics
      colleagues from Australia, Finland, Ireland, New Zealand, Scotland and the USA
      formed a research collaborative to validate the I-HIT in six additional
      countries. This paper will discuss the background, methodology, results and
      implications from the Australian I-HIT survey of over 1,100 nurses. The results
      are currently being analyzed and will be presented at the conference.

PMID- 19592875
TI  - Identification and usability of data-based nurse staffing indicators: a pilot
      study in Kuopio University Hospital.
AB  - OBJECTIVES: The pilot study is a part of the Magnet hospital research project in
      Northern Savo in Finland, which is a collaboration between the University of
      Kuopio and Kuopio University Hospital (KUH) in 2006-2012. The purpose was to
      identify, describe and assess nurse staffing indicators from the data system of
      KUH. Donabedian's structure-process-outcome model (SPO) and the preliminary nurse
      staffing model by Partanen were used as a framework. DATA AND METHODS: The data
      were a retrospective time series. The variables were extracted monthly from the
      hospital data of seven medical wards of KUH in 2006. The data consisted of
      information on 10 958 in- or outpatient visits in wards and administrative data
      of 117 nurses. The data were described statistically and graphically. The
      stability of the variables was tested. The optimal levels of the outcome and
      structure variables were determined. RESULTS: There were sixteen structural and
      six outcome variables, supported by models. The availability of outcome variables
      was quite poor. There were statistically significant changes in the stability of
      the variables. The optimal level of each outcome was achieved with varying
      degrees of the structure variables. CONCLUSIONS: Usable variables to measure
      nurse staffing were identified. New way of utilizing a longitudinal design was
      used as a method to evaluate nurse staffing levels and outcomes.

PMID- 19592876
TI  - Enhancement on infectious diseases nursing plan information system.
AB  - Based on researches, the most time-consuming nursing activities, in teaching
      hospital, are: room patrols, the blood pressure survey, the body temperature
      pulse breath survey, the nursing record maintenance. The nursing record is one
      way to communicate data. It can allow the medical service team to understand what
      measures the nursing staff once did for sickness, as well as responses from
      sickness. Nevertheless, it is the key component to utilize the record with a
      clinical nursing plan, so as to provide a proficient health management. Since the
      maintenance of nursing plan is costly and time-consuming, therefore, it is
      essential to establish the nursing plan information system, which can effectively
      promote the nursing quality. This research main body comes from one infectious
      disease division nursing plan information system, which was developed in 1992,
      and its data base covers entire courtyard compatibility and various faculties
      characteristic nursing plan. The nursing staff often complained that this system
      is not user-friendly, its contents are not comprehensive, and sometimes it does
      not let staff choose the right diagnosis. Therefore this research is based on
      history analysis and the questionnaire survey procedure first, the infectious
      disease nursing plan use number of times, the frequency and the project content,
      then by the literature scientific theory and result of the improvement group
      discussion together. The original 38 infectious disease division nursing plan
      will be expanded to 45 nursing plans. Moreover, the common 38 infectious disease
      code (ICD-9), and its corresponding diagnosis items, shall automatically appear
      in the disease diagnose code field, so it would be better off for the nursing
      staff to set up the nursing plan efficiently. Infectious disease division nursing
      plan information system utilization ratio is promoted 9.6-folds, according to
      research outcome. Each task consumes 3.68 minutes beforehand-including computer
      program operation, the printing of nursing plan, and now it turned out that it
      shall not take more than 3.08 minutes. The time efficiency is raised by 17% (0.6
      minute). Yet only 17% of the users are satisfied with it before, and now 74%
      nursing staffs are happy with the new tool.Therefore, it shall not only improve
      our service quality, but also save labor cost by using this information
      supplementary system.

PMID- 19592877
TI  - "When quality and computers meet" - construction of a computerized nursing
      quality indicators' scale for departmental self-monitoring and improvement of
      quality of care.
AB  - In recent years, computerized information systems have become one of the most
      important tools for promoting, developing and supporting quality improvement in
      healthcare. The unique contribution of these systems is related to the
      collection, storage and analysis of data as well as user-friendly and
      sophisticated access to end-users. Israel's nursing system has yet to fully
      implement the use of these systems in order to facilitate systematic measurement
      and improvement of nursing care quality.

PMID- 19592878
TI  - Survey of actual conditions of reasons for nurse calls: comparing a surgical ward
      and a medical ward.
AB  - We believe that nurse calls can play a role not merely as a means to convey
      patients' needs, but also as a medium to analyze and predict patients' needs
      using historical data of nurse calls. Therefore, we conducted a survey of actual
      conditions of nurse calls using "call history management system" developed for
      welfare institutions. The survey was intended to show patients' needs accurately
      by individually associating historical data, which can be collected through an
      information system, with reasons for calling, which usually cannot be collected
      automatically. Total quantities of nurse calls were 5,397 (174.1 per day, 4.59
      per day per person) in the Surgery Ward and 3,404 (109.8 per day, 2.85 per day
      per person) in the Internal Medicine Ward; the incoming calls to the Surgical
      Ward were more numerous than those to the Medical Ward. The most common reason
      for calling was "assistance related to toileting". During the day shift and
      evening shift, that reason was followed by "fluid management" such as finishing
      of fluid administration and fluid exchange.

PMID- 19592879
TI  - The mat study: global insight into the medication administration process.
AB  - An important aspect of global patient safety that has recently become a focal
      topic is preventing adverse drug events. As many as 7,000 patients die every year
      as a result of medication errors. (1) According to Bates, Spell, & Cullen,
      adverse drug events can cost up to an average of $8.4 million per year in a 700
      bed hospital, not including injury to patient or malpractice costs. (2) Errors
      can occur throughout the process of ordering a medicine, dispensing, retrieving,
      and administrating process. Safety measures have been implemented for physicians
      prescribing medication and pharmacists dispensing medication through MARs and
      CPOE. However, there is no safety net for nursing. Bar coding can offer that
      safety net and allow the nurse to verify "the five rights" of medication
      administration electronically. However, prior to implementation of a bar coding
      medication system (BCMA), it is important for an institution to gain full
      understanding of its current nursing work flow during the medication
      administration process.

PMID- 19592880
TI  - Development and testing of an observational method for detecting medication
      administration errors using information technology.
AB  - One-third of medication errors that cause patient harm arise from medication
      administration errors (MAEs). Research regarding rates of MAEs is limited and has
      predominantly relied upon voluntary incident reports or observational studies.
      Traditionally, observational studies have used paper-based data collection. This
      is time intensive and creates distraction from actual observation, limits the
      amount of information recorded and requires transcription of data. Incorporating
      the use of handheld computers for data collection in MAE studies provides an
      opportunity to overcome some of these limitations. Our objective was to develop
      and test an observational method which incorporated the use of data collection
      software on a personal digital assistant (PDA, a handheld computer) for use in
      observational studies to monitor MAEs within hospitals.

PMID- 19592881
TI  - Narrative text in structured documentation of medication risks and side effects.
AB  - Electronic patient records enable the use of patient data for clinical,
      administrative and research purposes. However, utilising electronic data requires
      a structured documentation model in which standardised nursing classifications
      are used. Finnish Care Classification (FinCC) is based on the Clinical Care
      Classification. FinCC version 1.1 used in this study contains Finnish
      Classification of Nursing Diagnosis and Interventions. This study aims to analyse
      how nurses have used narrative text to complement the documentation of medication
      risks and side effects when the Finnish Care Classification is used. The results
      of this study show that content of narrative text does not always correspond with
      the FinCC codes used. The content of narrative text does not follow the nursing
      process. Especially the use of nursing diagnosis seems to be difficult. This
      study indicates a need for continuing education about structured documentation.
      Further research is needed to analyse the relationship between nursing diagnosis
      and interventions as well as how other components are complemented with narrative
      text.

PMID- 19592882
TI  - Impact of BCMA on medication errors and patient safety: a summary.
AB  - PURPOSE: To summarize key recommendations and supporting evidence from the most
      recent studies evaluating the impact of bar coded medication administration
      (BCMA) systems, and the complementary technologies: Computerized Physician Order
      Entry (CPOE) and automated dispensing carts (ADC) in preventing medication errors
      and enhancing patent safety. SUMMARY: The IOM report in 2000 incited many
      healthcare institutions to implement e-prescribing and automated administration
      and dispensing of medications to prevent adverse drug events. Moreover, in 2004,
      the FDA call for bar codes on drugs and blood products has laid the groundwork
      for the widespread use of BCMA and the complementary technologies to reduce
      medication errors and improve patient safety. However, the implementation of this
      technology is a challenge because it introduces changes in the workflow and is
      costly as well. For a healthcare institution to think about adopting BCMA
      requires evidence supporting the recommendation to implement such technology.
      Challenges can be overcome by learning from others' experience with BCMA use. The
      evidence supporting the recommendation to properly use BCMA includes results on
      BCMA implementation in various healthcare facilities, and examination of the
      workarounds by nurses. CONCLUSION: The significant drop in medication errors rate
      achieved with the use of BCMA in various facilities presents a blueprint for its
      positive impact on patient safety. The observation measure to evaluate BCMAs use
      showed an increased rate of error detection because of the system ability to
      capture and record intercepted administration errors. However various workarounds
      by BCMAs users were detected. These workarounds were created to compensate for
      the flaws and inconvenient aspects of the barcode technology.

PMID- 19592883
TI  - Development of a computerized observational data collection tool for a medication
      error study.
AB  - The purpose of this study was to introduce the development of a computerized
      tool, called 'MedObs Collector' and its' qualitative usefulness in a medication
      error study. The requirements for a tool were driven from the medication error
      research design and users of five research assistants. The MedObs Collector was
      designed to support multi-user data input and automatic match between data
      records. MS Access(R) was used in implementation. We applied this tool to
      collecting and managing data in a clinical setting and received feedback from
      users. Through the informal evaluation we found several advantages in training
      and establishing reliability. It has also reduced the amount of time required for
      data entry.

PMID- 19592884
TI  - Framework for preventing accidental falls in hospitals - management plan for ADL,
      medication and medical conditions.
AB  - Prevention and reduction of medical accidents is essential. Among medical
      accidents, accidental falls remain a serious problem. While "assessment score
      sheets" have already been used in hospitals to prevent accidental falls,
      satisfactory results have not actually been achieved. In this study, we aim to
      establish a methodology for preventing accidental falls. We consider that the
      'management plan' for each patient includes three factors. A plan of instructions
      for patients on actions they can take for safety in their ADL (Activities of
      Daily Living) is essential as a base. Second, a plan to keep up with any short
      term change in a patient's state is needed, because the state of a hospitalized
      patient will usually be temporarily affected by medication and changing medical
      conditions. We develop a model for preventing accidental falls, which enable us
      to design appropriate management plan for each patient. Then, we develop a
      prototype system based on the designed model. Finally, we address the result of
      verification of the model, by applying the prototype system into actual cases in
      hospitals.

PMID- 19592885
TI  - Fall TIP: validation of icons to communicate fall risk status and tailored
      interventions to prevent patient falls.
AB  - This paper reports on the development and validation of a set of icons designed
      to communicate fall risk status and tailored interventions to prevent patient
      falls in hospitals. The icons will populate a fall prevention toolkit to provide
      actionable alerts to nurses, nursing assistants, and other interdisciplinary
      health care team members and educational materials for patients and families in
      acute hospital settings.

PMID- 19592886
TI  - Investigation of the load on the lumbar region in nursing technique's movements -
      relation between twist and surface electromyogram.
AB  - This study measured the twist angle of the lumbar region and the surface
      electromyogram (EMG) and examined their mutual relation to elucidate the degree
      and influence of factors of "twist" in nursing techniques as a cause of lower
      back pain. Using a goniometer (two-way angle and twist sensors) and an EMG(SX230;
      DKH Co., Ltd.), we conducted measurements by affixing the goniometer on the
      lumbar vertebral column and EMG sensor at four points of right and left sides of
      L2 and L4 (of the erector muscle of the spine). The measured nursing techniques
      were three common methods of "transferring a patient from bed to wheelchair,"
      which is said to impart a heavy load on the lumbar region. Results show that the
      correlation value between the twist angle rate and mean energy is likely to be
      greater, suggesting that the magnitude of the load on the lumbar region should be
      related to the twist speed rather than to the twist angle of the movement itself.

PMID- 19592887
TI  - Moving to a culture of nurse as knowledge worker and a new way of knowing in
      nursing.
AB  - In this paper, the authors speculate on the future of nursing practice as it will
      be informed by emerging technologies for the management of clinical information
      and knowledge and the generation of new understandings. It is postulated that
      without a concomitant effort to transform nursing practice, the fulsome benefits
      of electronic health records and associated tools will not be realized for
      nurses, other clinicians and patients. The path to creating a nursing practice
      culture of integrated knowledge management necessitates new thinking about
      clinical care delivery and an expansion of the ways of knowing in nursing. For
      the purpose of this paper, clinical practice transformation is defined as: moving
      beyond the form and function of nursing practice as we know it today by boldly
      advancing the redesign of clinical processes and being open to emerging
      transformative possibilities within society and healthcare through the use of
      technology.

PMID- 19592888
TI  - Glycemic control through computerized subcutaneous insulin calculators.
AB  - Sliding scale insulin (SSI) is a reactive therapy and does not maintain
      euglycemia in hospitalized patients. A combination of basal insulin, prandial
      insulin, and correction factor dosing provides a more consistent insulin state
      encouraging improved glycemic control. Intermountain Healthcare developed an
      application consisting of four calculators incorporating scheduled (basal and
      prandial) and correction-factor insulin. The result is a patient-specific order
      set with calculated insulin orders, a correction factor dosing table, and a
      carbohydrate dosing table. This paper describes the SQIC, access, usage
      monitoring, and challenges and solutions to the computerized decision support
      application created to replace SSI.

PMID- 19592889
TI  - RAFAELA Patient Classification System as a tool for management.
AB  - The RAFAELA Patient Classification System offers tools for the managers to follow
      the adequacy of resourcing through the Nursing Care Intensity per Nurse (NCI/N).
      The basic idea of the RAFAELA system is that the workload expressed as NCI/N is
      compared with the optimal NCI level for the ward. By creating systematic
      reporting on this indicator, managers can follow the workload level on different
      wards. The measurement tool is available to all nurses as well as to managers.
      Thus the staff can follow the results of the daily use of patient classification.
      Managers can use the data for staff allocation between different wards. As a
      result, the workload can be discussed and analyzed, and the consequences of
      challenging situations can be resolved. Together with the staff the managers can
      look for different solutions for the problems. The overall workload can be too
      high or too low or the variations of the workload can be too large. The overall
      aim is a workload on an optimal level. RAFAELA offers a multitude of solutions
      finding new ways to allocate working hours, networking with different wards,
      discussions with the persons who guide patient flow in the hospital or changing
      the number of nurses in the ward.

PMID- 19592890
TI  - Home care decision support using an Arden engine--merging smart home and vital
      signs data.
AB  - The demographic change with a rising proportion of very old people and
      diminishing resources leads to an intensification of the use of telemedicine and
      home care concepts. To provide individualized decision support, data from
      different sources, e.g. vital signs sensors and home environmental sensors, need
      to be combined and analyzed together. Furthermore, a standardized decision
      support approach is necessary. OBJECTIVE: The aim of our research work is to
      present a laboratory prototype home care architecture that integrates data from
      different sources and uses a decision support system based on the HL7 standard
      Arden Syntax for Medical Logical Modules. METHODS: Data from environmental
      sensors connected to a home bus system are stored in a data base along with data
      from wireless medical sensors. All data are analyzed using an Arden engine with
      the medical knowledge represented in Medical Logic Modules. RESULTS: Multi-modal
      data from four different sensors in the home environment are stored in a single
      data base and are analyzed using an HL7 standard conformant decision support
      system. CONCLUSION: Individualized home care decision support must be based on
      all data available, including context data from smart home systems and medical
      data from electronic health records. Our prototype implementation shows the
      feasibility of using an Arden engine for decision support in a home setting. Our
      future work will include the utilization of medical background knowledge for
      individualized decision support, as there is no one-size-fits-all knowledge base
      in medicine.

PMID- 19592891
TI  - eEvidence: supplying evidence to the patient interaction.
AB  - Nursing demands that all care offered to patients is appropriately assessed,
      delivered and evaluated; the care offered must be up to date and supported by
      adequately researched published evidence. A basic logic suggests that information
      and communications technology can help the nurse in maintaining his/her care
      provision to the highest level through presenting relevant evidence. The nursing
      need for evidence to support the delivery of care is a global phenomenon. Within
      the project this is demonstrated by the fact that the project lead is resident in
      England and the project is being carried out in Singapore with the help of the
      National University Hospital, the Alice Lee Centre of Nursing Studies and the
      School of Computing at the National University of Singapore. The project
      commenced in January 2008, this paper will present the background thinking to the
      project design and will describe the outcomes which will provide nurses with
      individual supportive evidence for their practice gleaned from quality assured
      sources. The project will use information and communications technology to
      provide the evidence on an individual basis. The paper will outline the four key
      elements of the project, these being the development of user (professional)
      profiles; the design and development of an automatic crawler search engine to
      deliver quality assured evidence sources and software design; there will be some
      mention of hardware design and maintenance which is the fourth key element.
      Within the paper, consideration will be given to the added value of the project
      to the nurses, their patients/clients, the research agenda and the employing
      organisation: The drive for information is determined by the nurses in clinical
      and community practice. Evidence available immediately at the point of
      intervention with patient/client. No patient information stored within structure.
      All technology and almost all support software already available. Additional
      information can flow both ways for quality and activity audits. Identification of
      areas weak in evidence requiring supportive research will be driven by practice.
      Immediate dissemination of new generic practices and principles can be delivered
      to each nurse on syncopation, removing the requirements for paper updates etc.
      Process can be transferred across all healthcare clinical professions In
      conclusion, information will be given on progress to date in terms of technical
      applicability and user acceptance by the nursing staff. In addition, an insight
      will be given as to managing a multiprofessional, multi-organisational project
      from a distance.

PMID- 19592892
TI  - An IT innovation for individualizing care: success with clinicians leading the
      way.
AB  - In 2004, the Knowledge-based Nursing Initiative (KBNI) began as a partnership
      between a university-based college of nursing, an informatics vendor, and a
      large, integrated health care system. The goal was to develop a process for
      translating evidence into actionable recommendations, embedding the
      recommendations into the computerized decision support and documentation systems,
      and supporting nurses' use of the nursing process to individualize care. This
      paper will describe the essential administrative, information technology (IT),
      educational and clinical support activities that were used to deploy this
      innovation into the electronic health record (EHR) and workflow of nurses on two
      acute care medical pilot units in July of 2008. The project supported every nurse
      to document their evidenced-based practice with each patient contact and populate
      the EHR database with rich, nursing sensitive, retrievable data for quality
      improvement and research. The results included verifying data reliability and
      validity, evaluating go-live preparation, and summarizing the qualitative and
      quantitative findings. Two critical factors that made this implementation a
      success were that the project had a transformational vision and that it was led
      by the clinical team and strongly supported by the IT team. The lessons learned
      in the adoption phase will be diffused to the rest of the health care system and
      beyond.

PMID- 19592893
TI  - Development and evaluation of ICNP-based Electronic Nursing Record System.
AB  - This study was conducted to cross-map nursing statements with International
      Classification of Nursing Practice (ICNP) Version 1 and to develop and evaluate
      ICNP-based Electronic Nursing Record System. Among the 7,631 nursing statements
      which were cross-mapped, 5,970(78.2%) nursing statements were completely
      expressed and 1,520(19.9%) statements were partially expressed. ICNP-based
      Electronic Nursing Record System was developed for the Asan Medical Center in
      Korea. Most nursing statements (6,671 of 7,931, 87.0%) and Most cross-mapped ICNP
      terms (965 of 1,015, 94.9%) were documented by user in all the units from July,
      2007 to August, 2008.

PMID- 19592894
TI  - Documentation of pain management with TT- 2000+ in May 2008 viewed from clinical
      nursing practice.
AB  - BACKGROUND: Electronic Patient Record (EPR) TT- 2000+ was implemented in Hospital
      Orton in January 2008. The software TT 2000+ was implemented in 2005. TT- 2000+
      enables structured and specifically defined documentation in clinical nursing
      practice. OBJECTIVES: To describe the use of pain management documentation into
      TT- 2000+ and how the results can be implemented into clinical nursing practice.
      Can the results be used in development of clinical nursing practice? How does the
      evaluation of pain reflect into the number of documentation? METHODS: The data
      were obtained from documentations made in May 2008 from patient groups that had
      undergone total hip arthroplasty and total knee arthroplasty. RESULTS: The number
      of total hip arthroplasty patients was 60 and total knee arthroplasty patients
      51. The total number of pain documentations with the group of THA's was 992 and
      with TKA's 913. DISCUSSION: Due to the circumstances in May 2008, the numbers of
      documentation into the TT- 2000+ are inadequate. Therefore, the documentation
      needs further research within a longer period of time. Undefined and unified way
      of maintaining and recording should be considered in processing information in
      clinical practice.

PMID- 19592895
TI  - Experience and nurses use of computerised decision support systems.
AB  - Computerised clinical decision support systems (CDSS) are increasingly being used
      by nurses to support their clinical practice. One of the factors which may affect
      how nurses use technology such as CDSS may be their clinical experience. This
      paper uses data from a wider study examining how nurses use CDSS to examine the
      role of experience in nurses' use of CDSS. Data was drawn from two sources; a
      secondary analysis of interviews from a study examining nurses' use of CDSS in
      telephone triage and the analysis of observations and interviews of nurses using
      CDSS in two case sites. Two themes arose from the analysis of the data; the
      integration of knowledge from CDSS and how experience affects CDSS use. The
      implications of these results are discussed in relation to our knowledge of the
      characteristics of the development of expertise in nursing.

PMID- 19592896
TI  - Classification of pressure ulcers: a systematic literature review.
AB  - Different classifications of pressure ulcer are in use making national and
      international studies on epidemiological issues as well as on effects of
      prophylactical and therapeutical interventions difficult. A systematic literature
      search identified 31 pressure ulcer classifications. Thirteen could be retrieved
      and were further analyzed. Six variants of the International Classification of
      Diseases (ICD) differ totally in number of classes, hierarchical structure,
      characteristics included, and level of detail. They share only the fact of a
      "pressure ulcer". Recommendations of expert organizations and clinical
      classifications differ as well. The currently introduced grade "suspected deep
      tissue injury" in the classification proposed by the US-National Pressure Ulcer
      Advisory Panel (NPUAP) is neither present in the European Pressure Ulcer Advisory
      Panel (EPUAP) one, nor in the ICD variants. Being aware of the reliability issue
      in pressure ulcer diagnosis and grading, the situation is appalling. Furthermore,
      stage adjusted quality assessment, prophylaxis and therapy ends with the borders
      of a classification. We call the WHO to initiate a harmonization of the ICD
      variants of pressure ulcer classification and to cooperate with experts'
      organizations in this field, particularly with regard to the development of ICD
      11. Reports on pressure ulcer should always mention the classification used.

PMID- 19592897
TI  - A mobile medicine decision support system for district nurses.
AB  - Inappropriate use of medicines increases the risk of hospital admissions for the
      elderly. Not only does this lead to unnecessary suffering for the patients but
      also incurs a great financial cost to the society. A medicine decision support
      system in a Personal Digital Assistant (PDA), with a barcode reader, can provide
      an overview of the patients' complete medicine use, and detect unsuitable drugs
      and drug combinations. Focusing on the elderly, our aim was to evaluate if a
      mobile medicine decision support system with a barcode reader is useful and user
      friendly for nurses in home care. The participants received a comprehensive
      overview from the patients' medicine use and noted drug-drug interactions,
      therapeutic duplications and warnings for drugs unsuitable for elderly people.
      The nurses regarded that the decision support system increased prevention and
      safety, was useful and user-friendly. Our findings suggest that most of the
      content and functions were regarded as important. Therefore, this decision
      support system might be a useful tool for district nurses.

PMID- 19592898
TI  - Frequency and types of alerts for antibiotic prescribing in a neonatal ICU.
AB  - Sepsis in neonates is a significant problem that carries with it severe morbidity
      and mortality. Managing antibiotics in this population is therefore an important
      issue. We studied clinical alerts currently in place to support antibiotic
      prescribing in a neonatal intensive care unit in order to ensure that appropriate
      information is being provided in a way that is consistent with current
      recommendations. Data were obtained from our alerts tracking database. Alerts
      were described according to triggering orders and clinician recipients. We found
      that alerts most commonly associated with antibiotics are providing critical
      information regarding lab results and patient factors necessary in preventing
      adverse effects of these drugs. Clinician recipients of alerts are those
      responsible for entering orders and the information is being provided at the
      point of care.

PMID- 19592899
TI  - Web-based learning resources - new opportunities for competency development.
AB  - Creating web-based learning environments holds great promise for on the job
      training and competence development in nursing. The web-based learning
      environment was designed and customized by four professional development nurses.
      We interviewed five RNs that pilot tested the web-based resource. Our findings
      give some insight into how the web-based design tool are perceived and utilized,
      and how content is represented in the learning environment. From a competency
      development perspective, practicing authentic tasks in a web-based learning
      environment can be useful to train skills and keep up important routines. The
      approach found in this study also needs careful consideration. Emphasizing
      routines and skills can be important to reduce variation and ensure more
      streamlined practice from an institution-wide quality improvement efforts. How
      the emphasis on routines and skills plays out towards the individual's overall
      professional development needs further careful studies.

PMID- 19592900
TI  - Getting eHealth into basic nursing education: report of the RCN information in
      nursing project.
AB  - This paper reports the results of a project undertaken in 2008 by the Royal
      College of Nursing's Information in Nursing Forum. The project, undertaken by the
      RCN IN Forum in association with the RCN Education Forum and the RCN Association
      of Nursing Students, was in two parts. The first part consisted of an on-line
      survey of nursing students to discover their "readiness" for working in an
      electronic environment. The second part consisted of a workshop for invited
      stakeholders - organisations responsible for commissioning and providing basic
      nursing education, regulators, nurse teachers, and nursing students themselves -
      the objective of which was to consider the results of the survey and other
      information, in order to develop a consensus on how best to incorporate eHealth
      issues into basic nursing education. The survey was undertaken during April 2008
      via the RCN website. Students were asked how well they felt their nursing
      education had prepared them for competencies set out in a previously published
      model curriculum. 1,120 students responded. 565 students who had used electronic
      patient records during their most recent clinical placement were asked about
      their experience. Students rated their basic computer skills much higher than
      their understanding of eHealth. While they felt competent to document assessments
      and care plans using paper records, few felt competent to do so using electronic
      records. Few know anything about telehealth (remote diagnosis and delivery of
      healthcare) or telecare (assistive technology in people's homes). Among those who
      had used computers in their most recent clinical placement there were clear
      breaches of the protocols designed to ensure security and confidentiality. Twenty
      seven invited participants attended the workshop held in October 2008, plus 12
      members of the participating Forums and relevant RCN staff. Following
      presentation and discussion of the findings of the survey, participants worked in
      three groups to identify and discuss issues arising from the survey, and to
      identify barriers using a Force Field Analysis. All participants agreed eHealth
      should be an integral part of nursing education and not an "add-on", and that the
      responsibility for "Getting eHealth into basic nursing education" had to be
      shared by university based educators, placement supervisors, and regulators.

PMID- 19592901
TI  - An analysis of published nursing informatics competencies.
AB  - Nursing informatics competency lists can provide a clear picture of required
      skills, knowledge, and attitudes needed for today's nursing workforce in a high
      tech environment. Many stakeholders such as employers and educators have a vested
      interest in defining nursing informatics competencies for nurses. The primary
      objective of this paper was to compare and contrast published nursing informatics
      competencies. A literature search was conducted using the terms "informatics
      competencies" and "nursing informatics competencies" via PubMeb and CINAHL for
      relevant articles. The search captured 37 articles; however, only six met the
      inclusion criteria set prior to the search. These six competency lists were
      reviewed for audience, sample size, design, categories used to classify
      competencies and operational examples of competencies. Findings revealed that
      there is variation among published informatics competencies in regard to content,
      presentation, and audience. A general list of competencies that can be utilized
      by nurses at all levels is needed. As a result nurses could operationalize and
      measure the skills, knowledge, and attitudes necessary to execute safe and
      effective nursing care in today's health care setting.

PMID- 19592902
TI  - Psychometric properties of the self-assessment of nursing informatics
      competencies scale.
AB  - The objective of this study was to examine the factor structure, internal
      consistency reliability, and responsiveness of the Self-Assessment of Nursing
      Informatics Competencies Scale (SANICS). Combined BS/MS nursing students (N=336)
      completed the 93-item scale, which was based upon published and locally-developed
      nursing informatics competency statements. Exploratory principal component
      analysis with oblique promax rotation extracted five factors comprising 30 items
      that explained 63.7% of the variance: clinical informatics role (alpha=.91),
      basic computer knowledge and skills (alpha=.94), applied computer skills:
      clinical informatics (alpha=.89), nursing informatics attitudes (alpha=.94), and
      wireless device skills (alpha=.90). Scale responsiveness was supported by
      significantly higher factor scores following an informatics course. This study
      provided preliminary evidence for the factor structure, internal consistency
      reliability and responsiveness of the 30-item SANICS. Further testing other
      samples is recommended.

PMID- 19592903
TI  - Nursing informatics for future nurse scholars: lessons learned with the doctorate
      of nursing practice (DNP).
AB  - The addition of the DNP created challenges that resulted in a re-evaluation of
      the leveling of informatics competencies across the nursing curriculum. The
      knowledge and skills needed by informatics nurse specialists was differentiated
      from those needed by three levels of nurses (entry level practitioner, advanced
      practice nurse, and nurse scholar (both PhD and DNP)). After a thorough review of
      the literature and examination of various competencies and definition for nursing
      informatics, a new model was proposed and guided the creation and implementation
      of a core course in informatics for DNP students.

PMID- 19592904
TI  - Australian Nursing Informatics Competency Project.
AB  - A study of Australian nurses on their use of information technology in the
      workplace was undertaken by the Australian Nursing Federation (ANF) in 2007. This
      study of over 4000 nurses highlighted that nurses recognise benefits to adopting
      more information technology in the workplace although there are significant
      barriers to their use. It also identified gross deficits in the capacity of the
      nursing workforce to engage in the digital processing of information. Following
      the release of the study last year, the ANF commenced work on a number of key
      recommendations from the report in order to overcome identified barriers and
      provide opportunities for nurses to better utilise information technology and
      information management systems. One of these recommendations was to seek research
      funding to develop national information technology and information management
      competency standards for nurses. This project has now received Federal Government
      funding to undertake this development. This project is being developed in
      collaboration with the ANF and the Queensland University of Technology. This
      paper will discuss the methodology, development and publication of the Australian
      Nursing Informatics Competency Standards Project which is currently underway and
      due for completion in May 2009. The Australian Nursing Informatics Competencies
      will be presented at the conference.

PMID- 19592905
TI  - Enhancing nursing informatics competencies and critical thinking skills using
      wireless clinical simulation laboratories.
AB  - Nursing students at New York City College of Technology are assigned client care
      experiences that focus on common alterations in health status. However, due to
      the unpredictability of client census within any healthcare facility, it is not
      possible for all students to have the same opportunity to care for clients with
      specific medical conditions. But with the use of patient simulators in a
      dedicated Clinical Simulation Laboratory setting, students can be universally,
      consistently, and repeatedly exposed to programmed scenarios that connect theory
      with the clinical environment. Outcomes from using patient simulators include
      improved nursing knowledge base, enhanced critical thinking, reflective learning,
      and increased understanding of information technology for using a Personal
      Digital Assistant and documenting care by means of an electronic Patient Record
      System. An innovative nursing education model using a wireless, inter-connective
      data network was developed by this college in response to the need for increasing
      nursing informatics competencies and critical thinking skills by students in
      preparation for client care.

PMID- 19592906
TI  - The emerging role of educational informatics.
AB  - Initial growth in the field of nursing informatics has centered primarily on the
      clinical setting. Much has been written about the systems developed and evaluated
      and possible new roles that one can play in the clinical environment. The
      educational arena has not fared as well. Early attention has been focused on the
      integration of educational technology or on competency-based skills in
      informatics according to program levels of students. This paper will focus on the
      emerging role of educational informatics. Examples will provide nurses with a
      better understanding of the roles played by the educational informaticist in
      crafting the science of nursing informatics to produce better nursing education
      outcomes.

PMID- 19592908
TI  - Educating a health terminologist.
AB  - An overview of competencies and suggestions for educating healthcare
      terminologists is presented. This new role in healthcare informatics requires
      formal and informal education that pays particular attention to the adult
      learner. Knowledge of terminology and informatics standards development is
      critical, as well as knowledge about the use of terminology management servers.

PMID- 19592907
TI  - Problem-based learning and e-learning methods in clinical practice.
AB  - The purpose of this study is to describe the curriculum development and
      introduction of problem-based learning pedagogy (PBL) in the undergraduate
      nursing education at Savonia University of Applied Sciences in Iisalmi unit. The
      main points to be described are the integration of PBL and e-learning methods and
      nursing students' learning outcomes in clinical practice. PBL pedagogy develops
      information literacy skills, critical thinking and evidence-based nursing skills,
      communication, co-operation and team working skills, problem solving and self
      assessment skills. Integration of PBL and e-learning methods in clinical practice
      has developed nursing competencies, reflection of learning and peer support of
      nursing students. The most important results are peer support, feedback and a
      teacher's encouragement when using e-learning methods.

PMID- 19592909
TI  - The potential of 3-D virtual worlds in professional nursing education.
AB  - Three-dimensional (3-D) virtual worlds (VWs), such as Second Life, are actively
      being explored for their potential use in health care and nursing professional
      education and even for practice. The relevance of this e-learning innovation on a
      large scale for teaching students and professionals is yet to be demonstrated and
      variables influencing adoption, such as increased knowledge, self-directed
      learning, and peer collaboration, by academics, and health care professionals
      requires empirical research.

PMID- 19592910
TI  - Improving the academic programming process in a school of nursing using
      computational modeling and simulation.
AB  - In recent years, academic institutions have been challenged to search for new
      methods to provide high quality education and research at an affordable cost.
      This study used a unique methodology, computational modeling and simulation, to
      investigate faculty productivity at a school of nursing from 2004 till 2007. A
      model of the academic programming process was built in Arena, a discrete event
      simulation software package. The model predicted significant improvements in
      baseline faculty percent effort (PE) after reducing variation in class
      distribution throughout the week, combining classes with enrollment of 10 or
      less, adding additional faculty and standardizing PE policies. Performance
      metrics for faculty productivity showed significant improvement post
      implementation of recommendations in 2007.

PMID- 19592911
TI  - Informatics curriculum integration for quality and safety education for nurses.
AB  - This paper describes the creation of an informatics curricular thread in pre
      licensure nursing education, using the informatics competencies defined by the
      Quality and Safety Education for Nurses (QSEN) collaborative. Several U.S.
      initiatives are calling for more rapid incorporation of informatics competencies
      into nursing curriculum. Baseline data are presented and plans to roll-out the
      new curricular approach discussed.

PMID- 19592912
TI  - The development of an incident event reporting system for nursing students.
AB  - Incident events may occur when nursing students are present in the clinical
      setting. Their inexperience and unfamiliarity with clinical practice put them at
      risk for making mistakes that could potentially harm patients and themselves.
      However, there are deficiencies with incident event reporting systems, including
      incomplete data and delayed reports. The purpose of this study was to develop an
      incident event reporting system for nursing students in clinical settings and
      evaluate its effectiveness. This study was undertaken in three phases. In the
      first phase, a literature review and focus groups were used to develop the
      architecture of the reporting system. In the second phase, the reporting system
      was implemented. Data from incident events that involved nursing students were
      collected for a 12-month period. In the third phase, a pre-post trial was
      undertaken to evaluate the performance of the reporting system. The ASP.NET
      software and Microsoft Access 2003 were used to create an interactive web-based
      interface and design a database for the reporting system. Email notifications
      alerted the nursing student's teacher when an incident event was reported. One
      year after installing the reporting system, the number of reported incident
      events increased tenfold. However, the time to report the incident event and the
      time required to complete the reporting procedures were shorter than before
      implementation of the reporting system. The incident event reporting system
      appeared to be effective in more comprehensively reporting the number of incident
      events and shorten the time required for reporting them compared to traditional
      written reports.

PMID- 19592913
TI  - Counselling of Problem Based Learning (PBL) groups through videoconferencing.
AB  - This paper addresses the teacher's use of videoconferencing in Problem Based
      Learning (PBL) counselling. In our paper at NI2006 we presented a study which
      addressed the students' experiences. This paper is based on a study in which both
      qualitative and quantitative methods have been used. Results from the study are
      presented and discussed. Our aim is to pinpoint some of the critical issues that
      should be met in the planning and the management of videoconferencing when used
      in counselling. The study shows that videoconferencing is well suited for
      counselling of PBL groups.

PMID- 19592914
TI  - Using social software to transform informatics education.
AB  - The increased availability of Web 2.0 tools, specifically social software, has
      changed how users interact on the web. Web 2.0 tools allow users to create, share
      and disseminate information and knowledge with relative ease. Web 2.0 tools, such
      as social writing, networking and bookmarking tools, are impacting not only how
      we educate students but also how nurses deliver patient care. This paper
      describes how an informatics education program is educating their students to use
      social software as learners as well as practicing informatics specialists.

PMID- 19592915
TI  - Creating experiential learning activities using Web 2.0 tools and technologies: a
      case study.
AB  - Learning is no longer an internal individual activity but occurs through networks
      and connections. The aim of this project was to teach online health informatics
      students to use Web 2.0 tools and technologies to form networks and connections
      through experiential learning assignments. Web 2.0 tools and technologies were
      evaluated using a criteria checklist prior to implementation for students
      enrolled in health informatics classes at the University of Kansas School of
      Nursing. Health informatics students have developed competencies using an instant
      message service, blogging, concept mapping, social bookmarking, and interacting a
      virtual environment. In the future, health care professionals will have to work
      in rapidly changing environments and keep abreast of new innovations and tools,
      learn to use those tools, and to teach others about the tools.

PMID- 19592917
TI  - Health informatics: moving from a discipline to a science.
AB  - This paper examines the historical definitions of Health (Biomedical)
      Informatics. It is clear that a majority of the definitions refer to Health
      Informatics as a discipline. Rather it can be argued that the maturation of
      Health Informatics is beginning to culminate in a distinct science. This progress
      need to be reflected in academic programs as well as our conferences and
      publications.

PMID- 19592916
TI  - Validation of the Impact of Health Information Technology (I-HIT) Scale: an
      international collaborative.
AB  - In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing
      Informatics Community developed a survey to measure the impact of health
      information technology (HIT), the I-HIT Scale, on the role of nurses and
      interdisciplinary communication in hospital settings. In 2007, nursing
      informatics colleagues from Australia, England, Finland, Ireland, New Zealand,
      Scotland and the United States formed a research collaborative to validate the I
      HIT across countries. All teams have completed construct and face validation in
      their countries. Five out of six teams have initiated reliability testing by
      practicing nurses. This paper reports the international collaborative's
      validation of the I-HIT Scale completed to date.

PMID- 19592918
TI  - Evaluation of a training program for counselors in contraception and prevention
      of STIs and a website-based support system.
AB  - In Japan, the incidences of pregnancy and sexually transmitted infections (STIs)
      are increasing among young people. To address these issues, we initiated the
      following steps: 1) processes supporting contraception and prevention of STIs
      were created for counseling and construction of an algorithm for that process; 2)
      a system was developed using a website to support the program for training
      counselors, and provide practical support during and after the training; and 3) a
      program for the counselor was developed and is being evaluated. The counseling
      process was visualized by an algorithm notion method developed by Tsuru et al.
      Participants registered on the website, enabling them to confirm the lecture
      contents, record their self studies and submit issues. In order to evaluate this
      program, a preliminary survey and short tests after the lectures were completed.
      Participants were nurse-midwives who graduated at a nursing university. 27
      participants were expected to complete the program. The answer ratios in the
      short tests were significantly improved compared to them in the preliminary
      survey. All participants submitted issues via the website. Further development of
      the system is planned so that the website can provide practical support by
      trained counselors and build on the accumulated practical results. Further
      refinement of the developed algorithm is required so that trained counselors can
      use it regularly via the website.

PMID- 19592919
TI  - Using Second Life to enhance ACCEL an online accelerated nursing BSN program.
AB  - To create a presence in Second Life (SL) the university college of nursing (CON)
      purchased four virtual islands in December 2007. The intent was to enhance
      distance education with immersion learning experiences for nursing students in
      SL. The Pollock Alumni House, classrooms, faculty offices, a library, a student
      welcome center, a public health office, a disaster scenario, a clinic, a
      hospital, and several patient avatars were created. Houses are being built for
      nursing students to experience different patient care scenarios during home
      visits. At least 20 nursing faculty and academic staff and three cohorts of
      accelerated nursing students (77) have avatars and have experienced class
      sessions. Faculty and students schedule office hours, engage in synchronous
      chats, and utilize the public health department and SL support groups for class
      exercises. Current exercises in the public health department include a module in
      which the student learns the role of the sanitarian. Students use a checklist to
      inspect restaurants and bars in SL. They are also able to view a video of an
      interview with a sanitarian. Another module introduces them to the WIC (Women,
      Infants, and Children) program. Future student activities related to public
      health include disaster planning, bioterrorism, evacuations, community
      assessment, windshield surveys, fund raising, and health education as well as
      other activities suggested by public health nurses and students. The
      possibilities are limitless because of the resources that exist in the virtual
      world, SL. The purchase of the first two islands, the initial buildings, and the
      creation of the public health department was funded by a research grant. Virtual
      environments offer many advantages for nursing education. Many nursing students
      say they learn best when they actually "do something," which indicates that they
      often prefer experiential learning. Rare but life-threatening patient situations
      can be experienced since the clinical environment can be realistically simulated.
      The student has the opportunity to practice repeatedly without causing harm to
      patients. During these simulations, active learning takes place, immediate
      feedback can be given for both correct and incorrect actions, errors can be
      corrected, and consistent experiences can be reproduced for all students. This
      technology is revolutionizing education and will meet the needs of the media
      savvy generations to come. It can also provide virtual experiences that nursing
      students may encounter in the clinical setting which are high risk and low
      volume, thus enhancing patient safety.

PMID- 19592920
TI  - An empirical study of end user computing strategy in promoting the nursing
      informatics in Taiwan.
AB  - Nurses today should not just passively use programs set up for them by MIS
      professionals, they are capable of creating their own applications to help them
      do their job. We proposed a framework used to develop a spreadsheet training
      strategy for nurses. Our experimental studies confirm that trained nurses can
      become spreadsheet application developers.

PMID- 19592921
TI  - The impacts of informatics competencies and user training on patient information
      system implementation.
AB  - User training of information systems is crucial for the employees. However, it is
      not only the basic skills of information technology that determine what kind of
      training is required for the implementation. This study describes the users'
      professional competence and the implementation training, including information of
      the computer user training and learning methods. The target group consisted of
      the employees trained first to implement electronic health record systems in the
      Central Finland hospital district (n=290). Statistical methods such as frequency
      and percentage distributions, mean values and cluster averages were used in the
      analysis. The sum variables were made up by using factor analysis. Respondents
      were mainly satisfied with the classroom teaching. Almost half of them had
      practised the use of information systems after the teaching in the training
      environment. Good learning results were obtained when practising with personal
      guidance.

PMID- 19592922
TI  - Information literacy: using LISTEN project strategies to equip nurses worldwide.
AB  - The 21st century presents a major challenge in the form of information overload.
      In a profession where new knowledge is ever expanding, nurse educators must equip
      nurses to find the information they need to provide safe evidence-based care.
      Information literacy and information technology competencies have become a
      priority in nursing education, but inconsistencies in definitions, frameworks,
      content, and design, combined with ill-equipped faculty have hindered the
      development of a transferable model geared toward improving nurses' information
      literacy. Challenges are compounded for nurses in developing nations, where
      access to information and training for information literacy are both problematic.
      This paper describes experiences from the LISTEN project, during the 1st year of
      a 3-year funded Nurse Education Practice and Retention grant. Designed to improve
      information literacy competencies of student and workforce nurses, using
      individualized learning via interactive web-based modules, LISTEN provides on
      its' website a Did You Know video dramatizing the importance of information
      literacy to nurses, and offers resources for information literacy, information
      technology, and evidence-based nursing practice. Preliminary findings from beta
      testing reveal the module content is realistic, complete, and logical. The
      website and video have generated worldwide interest. Future possibilities include
      nationwide implementation and adaptation for the international arena.

PMID- 19592923
TI  - Structured terminologies in clinical information systems: implementation through
      collaboration.
AB  - The structure and content of the dialog with a clinical end-user is a critical
      aspect of clinical information system use, data capture and retrieval, and
      efficient and effective health care. This dialog is driven ultimately by embedded
      structures and processes that: a) provide functional models of clinical
      expression in support of professional practice, and b) determine how structured
      terminologies ought to populate these models. Based on diverse practical
      experience, this study identifies challenges to implementing structured clinical
      terminologies, categorizing them by both stakeholder group and application area.
      Collaboration across all stakeholders and across a wide range of application
      areas is identified as a key ingredient to successful terminology implementation
      and use.

PMID- 19592924
TI  - An electronic portal to support using information to improve healthcare.
AB  - The Scottish Government supports a culture of knowledge management and
      organisational learning for nurses, midwives and allied health professionals
      (NMAHP). To help facilitate this the National eHealth Programme has developed a
      portal, Using Information - Improving Healthcare, to enable sharing of
      international and national good practice in information use. The portal provides
      short stories of how information has been used to improve healthcare or services
      via text, sound bites or video, with links to resources and people connected with
      these examples. Evidence based user success criteria and governance arrangements
      ensure that the site remains a high quality resource.

PMID- 19592925
TI  - Capturing business requirements for the Swedish national information structure.
AB  - As a subproject for the National Information Structure project of the National
      Board of Health and Welfare, four different stakeholder groups were used to
      capture business requirements. These were: Subjects of care, Health
      professionals, Managers/Research and Industry. The process is described with
      formulating goal models, concept, process and information models.

PMID- 19592927
TI  - Creating a governmental policy framework for adoption of an electronic health
      record.
AB  - Promotion and support of electronic health records and electronic information
      exchange through governmental policy development requires a framework that
      considers cost, benefits, barriers, risks and policies at the statewide level
      that might accelerate or retard adoption. Recommendations to underpin
      governmental policy involve financial incentives, technology adoption, legal and
      regulatory considerations and consumer education.

PMID- 19592926
TI  - Translation of SNOMED CT - strategies and description of a pilot project.
AB  - The translation and localization of SNOMED CT (Systematized Nomenclature of
      Medicine - Clinical Terms) have been initiated in a few countries. In Sweden, we
      conducted the first evaluation of this terminology in a project called REFTERM in
      which we also developed a software tool which could handle a large scale
      translation with a number of translators and reviewers in a web-based
      environment. The system makes use of existing authorized English-Swedish
      translations of medical terminologies such as ICD-10. The paper discusses
      possible strategies for a national project to translate and adapt this
      terminology.

PMID- 19592928
TI  - Capturing nursing information in the United Kingdom through use of a conceptual
      model.
AB  - The adoption in the United Kingdom (UK) of SNOMED CT means that the core
      activities of nursing will need to be described using standardized nursing
      languages. Work already undertaken in Bangor University has proposed a
      "Conceptual model for Nursing Information". These authors have argued that the
      use of this conceptual model allows nurses to describe and measure outcomes of
      nursing care, using standardized language, in such a way as to provide a maximum
      data set. This maximum data set captures the totality of nursing activity in such
      a way as to be highly relevant, not only to nurses, but to other key
      stakeholders, not least of whom is the patient. This paper will present how the
      model was developed, the progress to date, and the future challenges of
      integrating the model into mainstream nursing practice.

PMID- 19592929
TI  - The Finnish national eHealth archive and the new research possibilities.
AB  - Medical research requires information. Now this information is collected from
      various sources and the quality of information is often poor because of different
      coding and collection methods. In Finland we are now building the national
      archive to store all the patient information from both public and private service
      providers. We have started to design a medical research based on this archive
      taking, however, care of the privacy needs in the same time.

PMID- 19592930
TI  - Leveraging technology for research.
AB  - One of the most exciting promises of technology lies in the potential to support
      research on complex questions through the capture, maintenance and analysis of
      large data sets. This is especially true in cases where research involves
      multiple contextual variables such as organizational research. The possibilities
      for increasing our scope and reaching to global proportions when designing
      research projects is within reach. This paper reports the results of research
      conducted within the United States and yields useful lessons for application in
      other settings and countries.

PMID- 19592931
TI  - A leadership initiative to improve paraprofessional communication of changes in
      patient status.
AB  - As hospitals around the globe make the transition from paper to electronic
      communication and documentation systems, there is a need for examining the role
      that electronic and non-electronic systems play in promoting effective and safe
      communication practices between all members of the health care team. We report
      here the strategies we have adopted to integrate a structured communication
      framework into the clinical workflow of paraprofessional providers as a means to
      support safe practices, to promote teamwork and to provide a key foundation for
      implementation of electronic clinical documentation.

PMID- 19592932
TI  - Developing a cost-effective home care management support system for small nursing
      homes in Taiwan.
AB  - Home care is important in Taiwan but most of the institutes are small and cannot
      afford computerization. We develop a support system based on InterRAI case
      management system using Excel VBA which is the most "free" application in
      institutes. The prototype system shows promising.

PMID- 19592933
TI  - Introducing nursing informatics and innovation into a professional practice
      model.
AB  - The American Medical Informatics Association has recognized the need to educate
      10,000 healthcare professionals in health informatics by 2010. This is one
      organizations effort to integrate nursing informatics, innovation and competency
      into clinical nursing practice.

PMID- 19592934
TI  - Implementation of information technology in nursing practice - challenge for
      management in psychiatric nursing.
AB  - The implementation of information technology (IT) applications in nursing
      practice requires systematic investments and guidance. A collaborative
      organisational culture, and systematic and close clinical and administrative
      cooperation during the implementation process support the acceptance of IT among
      users in organisation. Although knowledge of IT projects management exists, there
      is a lack of knowledge about nursing management in IT implementation processes in
      psychiatric nursing.

PMID- 19592935
TI  - The evaluation of the nurses' work performance after nursing information system
      implementation in one medical center in Taiwan.
AB  - The purpose of this study was to evaluate the nurses' work performance before and
      after implementation of two nursing information subsystems: Patient Admission
      Nursing Documentation(PAND) and Physical Examination Documentation(PED) in 2351
      beds medical center in Taiwan. Nurses' work performance was measured by time
      observation. The results of research showed that PAND increased the nurses' work
      performance 19.7% and PED increase the nurses' performance 2.8%.

PMID- 19592936
TI  - Using electronic patient record with PDA, benefits and nursing staffs' know-how
      to use technology.
AB  - Research is ongoing looking for new health care processes regeneration and
      rationalisation. Instrument and tool technology has come to health care while
      patient documents have become electronic. The process has to make sure, that
      patient records are of a high quality and all information readily available if it
      is to improve patient care.

PMID- 19592937
TI  - The effect of the emotional intelligence on job satisfaction.
AB  - People with high emotional and social capacity, people who can take them under
      control, understand and manage emotions of others expertly are more advantageous
      both in their private and professional lives. Under this scope, in order to
      investigate the effect of the emotional intelligence of nurses and midwives, who
      consist an important manpower in the health system, to their job satisfaction, an
      investigation has been conducted in Fethiye State Hospital with 80 individuals.
      Of the workers investigated, 36.3% were in 21-30 age group, 62.5% were 2 years
      college graduated, 98.8% were clinical nurses, 36.3% worked since 6-10 years. It
      was found that total emotional intelligence of the workers was low (X=22.54,
      SS=5.14), and average job satisfaction levels were middle level (X=15.62,
      SS=3.27). A positive association was found between the emotional intelligence and
      job satisfaction. As a conclusion, the relationships between the demographic
      variables and emotional intelligence and job satisfaction were evaluated in the
      study.

PMID- 19592938
TI  - Examination of nursing dependency for admission fee and measurement of nurses'
      work load for nursing care.
AB  - In April 2006, a system called seven-to-one nursing system was newly introduced
      in acute medicine which requires intense nursing care. In April 2008, a survey
      was conducted using "Assessment Sheet regarding Severity of Disease / Degree of
      Necessity of Nursing Care at General Wards", and obligation was established to
      fulfill certain requirements in medical institutions which collect the basic
      admission charge for the seven-to-one system. This survey is not a tool developed
      to investigate the amount of care required for patients but to measure the
      standard for the facility level. We report the findings from the comparisons of
      survey results for the amount of care provided to individual patients according
      to "The Classification of Degree of Nursing Care, Kagoshima University Edition".

PMID- 19592939
TI  - Nursing point of care documentation for the evaluation of human quality.
AB  - Nurses must have a point of care documentation method to share health information
      and transmit nursing data. Health information exchange using an online metadata
      registry allows nurses, health professionals, hospital administrators, and
      diverse information systems to make significant strides towards improving health
      outcomes and human quality of care. Health information exchange using point of
      care documentation supports research methods to determine the cost of nursing
      service as well as supports the professional assessment of our significant
      contribution to human quality and care outcomes in electronic health record
      systems.

PMID- 19592940
TI  - Development of the incident reporting system using the nursing administrative
      database.
AB  - A role of incident reporting system has become more important for improving of
      the patient safety. However, the more various causes managers seek for, the
      longer time healthcare providers send to report near-miss/ medical errors. The
      purpose of our work was to try to develop "the incident reporting system"
      utilized the nursing administrative database. As a result, we found that the
      system would make us spend less time to report medical errors and easy to analyze
      of the nursing care structure. The system using the nursing administrative
      database is effective to improve the patient safety rationally.

PMID- 19592941
TI  - Home telehealth electronic health information lessons learned.
AB  - Interoperability issues are critical for home telehealth applications, electronic
      health records, electronic medical records, and personal health records. Issues
      of interoperability affect clinical decision-making and clinician information
      synthesis. The ability to exchange data collected in the home with an electronic
      medical record has been positively related to improvements in process outcomes
      for chronic illness. However, to realize this benefit, risk must be minimized.
      Evaluation of interoperability challenges and their potential solutions supports
      data-driven risk management decisions.

PMID- 19592943
TI  - The use of mobile computational technology in the nursing process: a new
      challenge for Brazilian nurses.
AB  - The purpose of this study was to analyze the use a hand-mobile device with
      integrated wireless network interface to help nurses document the nursing
      process. The system is structured in five modules allowing the nurses to access
      and document data related to vital signals, hydroelectrolytic balance, assessment
      and nursing prescription at the point-of-care with transmission of data in real
      time. The results demonstrated that the mobile computer technology provided
      mobility for nurses and facilitated communication and documentation of care. In
      addition, real time documentation proved to be more efficient than a manual
      documentation system.

PMID- 19592944
TI  - The assessment of the mobile nursing cart in hospital adopting.
AB  - The purpose of this article was to express our assessment in mobile nursing cart
      adoption. The result shows the proper mobile nursing cart for the 150-160 cm
      height and 45-50 kg weight nurses should including below requirements 1. the
      height should be 95-100 cm, 2. the total weight should be less then 60 kg, 3. the
      lowest height of the notebook arm should be 90 cm away form the ground, 4. the
      power supply time should be more than six hours, 5. the computer screen size
      should be 15 inch, 6. the cart wheel size should be 5 inch. These should be the
      consideration for nursing managers to purchase mobile nursing carts in the
      future.

PMID- 19592945
TI  - Developing internet-based health services in health care organizations.
AB  - It is often said that we are living in an information society and information
      technology (IT) is a normal part of life in many fields. But IT is not used
      effectively in health care. The purpose of this study was to survey what kind of
      Internet-based health services and related electronic services are offered to
      clients by the web-pages of health care organizations in Finland.

PMID- 19592946
TI  - Second Life and health information.
AB  - Second Life (SL) is emerging as a repository of health information. The purpose
      of this study was to determine the number of places and groups that offer
      specific health information in SL. A retrospective analysis of SL places and
      groups was conducted for cancer. Findings indicate that more cancer information
      is available from groups than specific places in SL. All current and future
      cancer information will need to be evaluated for reliability and efficacy.

PMID- 19592947
TI  - The essential elements of caring when building innovative service in South
      African township.
AB  - When developing digital health care services there is a need for close
      cooperation between native and non-native developers. Via educating local people
      it is possible to find out health needs of families and develop an appropriate e
      services.

PMID- 19592948
TI  - Latina breast cancer survivors informational needs: information partners.
AB  - The ability to access and understand health information is becoming more critical
      to managing one's own health and illness. Informatics tools are increasingly the
      central resources for responding to these needs. But just as information is
      culturally bound, so are the tools used to access it; both are bounded by the
      contexts in which they are situated. Latinas face more barriers in accessing
      needed information due to cultural, linguistic and health access inequities in
      the US. Although breast cancer rates for Latinas are lower than for non-Latina
      white women, they are more likely to have a more advanced stage at diagnosis and
      poorer quality of survivorship. Few studies have explored Latina breast cancer
      survivors' information needs & strategies. This community-based study focused on
      Mexican American women with breast cancer and explored their health information
      experiences, needs, and strategies; it examined their perceptions of how their
      relationships with providers influenced how information was accessed and
      utilized. Managing information was not an individual responsibility for any of
      these women. All of these women had access and used the Internet either directly
      or through their support networks. All emphasized the importance of having a
      select support network of people (information partners) for receiving, searching,
      and interpreting all health information about their illness. If information
      partners are strategies preferred by Latinas, then we must refocus our assessment
      of e-health literacy competencies on networks rather than individuals.

PMID- 19592949
TI  - Between personal health record website and portable medical health record: an
      online data transformation interface.
AB  - Web-based Personal health record recently brought out the whole world attention
      by two famous vendors involved in this battle field. The convenience and ubiquity
      of user-end data management influence the user's will greatly. This study is
      based on the idea of easy data transfer from the portal device to the web-based
      personal health record, and further more this can promote the use of personal
      health record and assist more people manage their own health.

PMID- 19592950
TI  - Analyzing and modeling of the web-based self care record system for hypertension
      patients - focused on blood pressure and drug management.
AB  - This study reviews and analyzes three web-based self care record systems for
      hypertension patients that are selected by many Korean medical web sites
      suggesting the new web-based self care record system for hypertension patients.
      Also, this study can aim to increase the effectiveness of the web-based self-care
      record system focused on blood pressure and drug management for hypertension
      patients. Three web-sites (National Hypertension Center;
      http://www.hypertension.or.kr, Korea Hypertension Diabetes Deagu Institute;
      http://khyddi.cdc.go.kr, Health Korea http://www.healthkorea.net) were selected
      during the period from April 1 to April 7, 2008. This study represents the
      comparative analysis table of three web-based self care record systems for
      hypertension patients and the constructed system flow diagrams that were drew by
      MS Visio 2003.

PMID- 19592951
TI  - When and why do people post questions about health and illness on Web 2.0-based
      Q&A sites in Japan.
AB  - Web2.0-based Q&A sites such as Yahoo! Answers and OKWave are the fastest-growing
      sites in Japan. Such sites exploit user-generated content and information-sharing
      methods and have established point systems and user ratings to reward
      participation. We analyzed the questions and answers concerning health and
      illness posted on these sites. We found that the people who posted questions
      desired to obtain information related to their health problems from various
      sources, and to seek validation of this information not only by experts but also
      by people who have undergone similar experiences.

PMID- 19592952
TI  - User needs on Nursing Net (The Kango Net) - analyzing the total consultation page
      - http://www.kango-net.jp/en/index.html.
AB  - People are required to take in and comprehend a massive amount of health
      information and in turn make some serious decisions based on that information.
      We, at St. Luke's College of Nursing, provide a rich selection of high-quality
      health information, and have set up Nursing Net (The Kango Net:Kango is Nursing
      in Japanese). This website provides information for consumers as well as people
      interested in the nursing profession. In an attempt to identify the needs of
      users, this study conducted an analysis of the contents on the total consultation
      page. Many readers voted that responses to nursing techniques and symptoms
      questions proved instrumental in their queries. Based on the results of this
      study, we can conclude that this is an easy-to-access, convenient site for
      getting health information about physical symptoms and nursing techniques.

PMID- 19592953
TI  - Empowerment among athletes - an e-survey design.
AB  - This study focus on a healthcare system integrating citizens orientation towards
      a healthy sports active lifestyle in combination with an individual health
      information, to prevent them from sports injuries and to empower them in an
      everyday context. Sports give quality of life, but often result in injuries. In
      this survey population of 1,320 athletes, 90% had sports related injuries and 80%
      had received medical treatment. An e-survey investigates how the athletes use IT
      in relation to health and is a descriptive research into investigating specific
      indicators of individual empowerment.

PMID- 19592954
TI  - Personal health notes: lessons learned.
AB  - The health care system is characterized by fragmentation and specialization which
      challenge the possibility for patients to be well-informed about and involved in
      their health care. The present study contributes to an in-depth understanding of
      how we can use patients' own personal health notes to learn about the health care
      information system and patients' experience of multiple encounters. The personal
      health note shows different aspects of the health care labyrinths considering the
      inconsistency as well as discontinuity of the information.

PMID- 19592955
TI  - Evaluation of the completeness of the nursing process for patients having
      gastrectomy using electronic nursing records.
AB  - The purpose of this study was to evaluate recording completeness of the nursing
      process. We compared nursing statements documented at the time when the
      Electronic Nursing Record (ENR) system, based on the ICNP, was implemented in
      2004 with those documented in 2007. The ENRs for 35 gastrectomy patients in each
      year were selected for evaluation. The selected data were 11,822 nursing
      statements in 2004 and 27,870 in 2007. The results indicated a significant
      increase in the completeness of the nursing process in 2007. In addition, the
      number of nursing diagnosis increased by 5.1 times. The most contributing factor
      for this increase is assumed to be nurse education.

PMID- 19592956
TI  - Analysis of the gap between nurses' expectations and satisfaction on a home-made
      discharge planning system.
AB  - The objective of this study was to evaluate the nurses' expectations and
      satisfactory on this system. A questionnaire composed of ease-to-use and
      usefulness questions under Expectation before Implementation, Perception after
      Implementation and Satisfaction was designed for evaluation. We observed that
      even the system was designed with very simple IT techniques and passive
      cooperation with IT people, it could still positively valued by the users if they
      could participate the entire process. However, more IT resources and better team
      work is important to design a system which can meet users' expectation.

PMID- 19592957
TI  - What makes nurses perceive differently on the usability of same system?
AB  - Kardex system is important to provide rapid instructions for individual nursing
      care so it is important to measure and understand user's perceived usability of
      that system in order to make correct improvement. We evaluated 51 nurses'
      perceived ease to use and usefulness of the system and found the perceived
      usability could be affected by their computer skills, units, and shift report
      type.

PMID- 19592958
TI  - Predictive modeling of dental pain using neural network.
AB  - The mouth is a part of the body for ingesting food that is the most basic
      foundation and important part. The dental pain predicted by the neural network
      model. As a result of making a predictive modeling, the fitness of the predictive
      modeling of dental pain factors was 80.0%. As for the people who are likely to
      experience dental pain predicted by the neural network model, preventive measures
      including proper eating habits, education on oral hygiene, and stress release
      must precede any dental treatment.

PMID- 19592959
TI  - RFID and medication care.
AB  - Dynamic healthcare needs new IT innovations and applications to be able to treat
      the rapidly growing number of patients effectively and safely. The information
      technology has to support healthcare in developing practices and nursing patients
      without confronting any complications or errors. One critical and important part
      of healthcare is medication care, which is very vulnerable for different kind of
      errors, even on fatal errors. Thus, medication care needs new methods for
      avoiding errors in different situations during medication administration. This
      poster represents an RFID-based automated identification system for medication
      care in a hospital environment. This work is a part of the research project
      MaISSI (Managing IT Services and Service Implementation) at the University of
      Kuopio, Department of Computer Science, Finland.

PMID- 19592960
TI  - Health care information systems - the outcomes of the integrated use of health
      information.
AB  - The objective of this study is to formulate a clearer picture of how a regional
      healthcare information system affects the completeness of patient health care and
      health care delivery. The purpose is to study how the implementation of regional
      health information systems has influenced outcomes in health care delivery in one
      hospital area in Finland. The essential concepts in this study are health care
      information systems and outcomes. The research consists of four different phases.
      Research material will be processed through qualitative and quantitative research
      methods and statistical tests.

PMID- 19592961
TI  - An evaluation study on the nurse shifting information system.
AB  - Nurse shifting has long been a headache for nurse management. The traditional
      paper-and pencil shifting is time consuming and inefficient due to the huge work
      shift data and other considerable factors, such as overlap shifting, overtime
      shifting or even overleap shifting. In order to focus on the well-being of the
      patients and improve the quality and efficiency of nursing care, a computerized
      nurse shifting information system is essential.

PMID- 19592962
TI  - A strategy for preparing contents for a computerized documentation system.
AB  - One of the challenges hospitals face with in computerizing a documentation system
      is preparing documentation contents in a way that sufficiently reflects existing
      best nursing practice while reconciling heterogeneous formats and expressions of
      the same contents across settings. We have identified a strategy to support
      analyzing the existing documentation contents collected from various paper forms
      across Partners HealthCare System (PHS). We introduce the process and the tool
      that we have developed to support the content preparation efforts.

PMID- 19592963
TI  - Developing a clinical informatics system which supports a model of partnership
      among caregivers, patients, and families.
AB  - Partnership Care Delivery is an evidence-based practice model being developed at
      this institution. It emphasizes interdisciplinary collaboration, in which all
      members of the healthcare team work with the patient as active participants in
      care processes. In order to achieve true partnership among disciplines, and to
      engage the patient and family, it was important to create supportive clinical
      informatics. The new system will provide access to scientifically sound
      information and empower synergy of interdisciplinary teams united as partners
      with patients and families through shared information.

PMID- 19592964
TI  - Connecting humans and health through health information exchange.
AB  - To address healthcare quality, efficiency and safety, a national health
      information technology (IT) initiative was announced by the President of the
      United States in 2004 to make Electronic Health Records (EHR) available to most
      Americans within 10 years. The National Health IT Agenda has advanced with
      recognition of interoperability standards for Personal Health Records (PHR) and
      Population Health information exchange. This session will illustrate the national
      processes, timeline, stakeholders and benefits of adoption of interoperability
      standards to enable health information exchange.

PMID- 19592965
TI  - Requirements analysis for HL7 message development in poison control center.
AB  - HL7 is the commonly accepted messaging standard for achieving interoperability
      among information systems. Until now, no analysis has been done on how poison
      control data can be matched in HL7 messages. The purpose of this study was to
      create a preliminary domain analysis model which can be used to identify the data
      required to message poison control data in HL7 messages.

PMID- 19592966
TI  - Nurses' experiences of and opinions about using standardized care plans in
      electronic health records.
AB  - The nurses in the study had generally positive attitudes towards use of
      standardized care plans, use of standardized care plans in EHR and quality
      standards for clinical practice. They considered that these procedures facilitate
      their work and improve the quality of care.

PMID- 19592967
TI  - The application of data mining skill on identifying critical factors in the web
      based incident reporting system.
AB  - The purpose of this is study was to apply data mining skill to explore the fall
      critical factors. Feature selection and variable screening were applied on the
      total of 725 incidents as the first two screening steps. The neuronetwork model
      was - MLP (multilayer perceptron) 19-7-2 with sensitivity and specificity as
      50.00% and 84.42, respectively. The result could be utilized for further
      intervention studies to validate the findings.

PMID- 19592968
TI  - Comprehensiveness of EPR documentation by home care nurses.
AB  - Nursing documentation of home health care was audited in a sample of 91
      electronic patient records. The audit showed that documentation by home care
      nurses was unstructured and incomplete in terms of the nursing process. This
      supports similar findings from earlier research, and prompts questions about the
      feasibility of the nursing process as a framework for nursing documentation in
      practice.

PMID- 19592970
TI  - The development of the nursing observation master file.
AB  - An observation by the nursing, symptom views by the doctor and result of
      examinations can be said to be terms expressing a patient status. We collected
      names of nursing observation items and result notation terms in bottom up from
      real practice. We performed Structuring and standardization of "an observation
      item name" and "the result notation" with 8 step method. This master transcribes
      an observation result in 1 to 1 for an observation name. On this account we put
      it as another item when result notation is different to the same observation
      name. Collected terms are 1,653 cases with a set of an observation item name and
      the result notation.

PMID- 19592971
TI  - The development of the nursing action master file.
AB  - The nursing action master was developed through collecting terms used by the
      nurses. The nursing action terms were classified in 2 of the basics and
      specialty. The nursing action master consists of four hierarchical structures.
      Serial numbers and ID are set in every hierarchy. It started from 2006 to supply
      the master and it is revised every year. The number of the publication records is
      1,053 basic nursing practice standard terms.

PMID- 19592972
TI  - The development of method for continuous improvement of master file of the
      nursing practice terminology.
AB  - Nursing Action Master and Nursing Observation Master were released from 2002 to
      2008. Two kinds of format, an Excel format and a CSV format file are prepared for
      maintaining them. Followings were decided as a basic rule of the maintenance:
      newly addition, revision, deletion, the numbering of the management and a rule of
      the coding. The master was developed based on it. We do quality assurance for the
      masters using these rules.

PMID- 19592973
TI  - Identifying unit-specific nursing demands using Nursing Interventions
      Classification (NIC).

PMID- 19592974
TI  - Cross-mapping the Finnish Classification of Nursing Diagnosis, Nursing
      Interventions and the Oulu Patient Classification.
AB  - The structure of nursing documentation in Finland is based on the nursing process
      model and nursing diagnosis, interventions and outcomes are documented using a
      standardized nursing terminology. Patient related information is produced and
      stored in an electronic form at multiple sites. Patient care intensity
      classification is one of the essential pieces of nursing core data belonging to
      the structural data of an electronic patient record supported by the Ministry of
      Social Affairs and Health. The purpose of this paper is to describe the process
      of cross-mapping Finnish Classification of Nursing Diagnosis/Needs (FiCND),
      Nursing Interventions (FiCNI) and the most commonly used patient intensity
      classification in Finland, the Oulu Patient Classification (OPC). These databases
      enable evaluation, analysis and utilisations of data for administrative and
      research purposes. The end product is a cross-mapped classification material in
      The Institute for Health and Welfare (before National Research and Development
      Centre for Welfare and Health, STAKES) to use in every electronic patient record
      systems in Finland.

PMID- 19592975
TI  - Nursing standardized documentation in Kuopio University Hospital.
AB  - The national Nursing Minimun Data Set (NMDS) based on the nursing decision making
      process, nursing core data (NMDS) and Finnish Care Classification (FinCC) were
      defined in Finland in the National Nursing documentation project in which Kuopio
      University Hospital has taken part among other health care organizations. The
      education and implementation of FinCC, which has been considered useful for
      nursing practise, is going on in Kuopio University Hospital. The statistics and
      the reports provided during the project have been beneficial to nursing
      management, planning, education, research, and quality assessment.

PMID- 19592976
TI  - Congruence between nursing problems in nursing care plans and NANDA nursing
      diagnoses.
AB  - This study abstracted nursing problems documented in cancer patients' nursing
      care plans to analyze (1) which nursing problems were documented and (2) the
      degree of congruence between the abstracted problems and NANDA nursing diagnoses.
      236 unique nursing problems were identified and could be mapped to 32 NANDA
      nursing diagnoses. However, only 4.3% had a precise match with NANDA, Thirty
      eight percent were classified as similar and the rest were broader, narrower or
      no match. Thus NANDA only partially covered problems written by nurses in the
      care plans for this group of patients.

PMID- 19592977
TI  - Enhancement of interoperability of disaster-related data collection using
      Disaster Nursing Minimum Data Set.
AB  - Data collected by nurses have the potential to aid in the disaster response if
      the necessary information can be extracted. The Disaster Nursing Minimum Data Set
      is proposed to strengthen the interoperability of information and data sharing
      between agencies to improve relief services to individuals and communities
      affected by a disaster. This study will examine disaster-related data elements
      need to be collected by all relief agencies to facilitate interoperability and
      secondary use of data for research and disaster management.

PMID- 19592978
TI  - An ontological approach for translating the ICNP.

PMID- 19592979
TI  - Omaha System data: methods for research and program evaluation.
AB  - Researchers are developing methods to evaluate health care quality and
      effectiveness using health informatics data sets. Standardized taxonomies such as
      the Omaha System are being used in computerized documentation systems to generate
      data on client assessments and health care services. Questions such as prevalence
      of client problems, care utilization, differential intervention effectiveness,
      and problem-specific client outcomes can be investigated. Approaches for
      analyzing Omaha System data are emerging in the literature and in practice
      settings, and will be described in this poster.

PMID- 19592980
TI  - An exploratory study on the health information terms for the development of the
      consumer health vocabulary system.
AB  - This study is to find out the difference between consumer vocabulary and medical
      vocabulary. The rate of mapping between the consumer vocabulary for health
      information and the medical vocabulary was not to be high. The terms that
      consumers use should be researched to understand their morphology and features,
      so that it will increase the accessibility of consumers to the medical and health
      information they need.

PMID- 19592981
TI  - The adoption of a controlled nursing vocabulary in Finnish scientific journals.
AB  - "Hoidokki" is a Finnish controlled nursing vocabulary for indexing and
      information retrieval purposes. Its second edition includes nearly 1000 terms. In
      this study, the congruence between the key words of three Finnish scientific
      nursing journals and the vocabulary was explored. Also, the content of the
      vocabulary was validated. The data included key words (N=208) used in 49 articles
      of three scientific journals in 2006. Two experts used content analysis to judge
      each key word and inter-rater reliability was calculated. Delphi-method was used
      to evaluate the potential new terms.

PMID- 19592982
TI  - Developing a model for elderly care plans.

PMID- 19592983
TI  - Exploring the encodability of comprehensive discharge information with the
      Unified Modeling Language.
AB  - Ineffective discharge processes often break the continuum of care, adversely
      affecting patients' outcome. In order to overcome such challenges and provide
      continuity of care to patients, an effective and smooth discharge process is
      important. A discharge information system that automatically processes data
      elements entered for discharge information is essential. In this preliminary
      study, a discharge information model was partially developed and encoded using
      UML, in order to form the foundation of an automated system.

PMID- 19592984
TI  - The development and the trial of the Nationally Standardized Electronic Nursing
      Documentation (NSEND) in Southern Savos Hospital district.
AB  - Starting 2003 the target in Mikkeli Central Hospital was to develop a common
      platform for electronic nursing documentation. Evaluation of the Nursing
      Management Minimum Data Set (NMDS) was carried out twice: 2003 and 2004, this
      provided a picture as to whether the nursing process assisted in the planning of
      nursing care. NSEND education started 2003 and has been carried out
      systematically since.

PMID- 19592985
TI  - Trial to structuralize and IT-systematize home-visit nursing based on PCAPS for
      quality improvement.

PMID- 19592986
TI  - Monitoring collaborative practice guideline access: initial steps to define
      effect on patient outcomes.
AB  - Over the past decade Intermountain Healthcare (Intermountain) developed the
      Collaborative Practice Guidelines (CPGs) as an e resource to direct bedside care
      delivery. The intent was to decrease care variability and improve patient
      outcomes. The CPGs provide pertinent clinical knowledge at the point of care.
      Intermountain clinicians are responsible to deliver care based on the best level
      of evidence available as reflected in the CPGs. Data regarding access was
      requested by Intermountain leaders to begin answering the question whether the
      CPGs have any effect on improving patient outcomes.

PMID- 19592987
TI  - The systematic review of effective interventions to promote collaboration between
      families and social and health services.
AB  - The increasing need for support and the fragmented nature of the service system
      challenge us to develop services for children and their families. Child and
      family services are provided by the public, private and third sectors, which
      according to research have little or no reciprocal co-operation. The review
      produced information on co-operation interventions used by service providers in
      the field of health care, social care and education. The current evidence base is
      too heterogeneous and sparse to draw conclusions on the overall effectiveness of
      interventions to co-operation. Further high quality studies examining the
      effectiveness of co-operation interventions are required.

PMID- 19592988
TI  - Electronic standard care plans of home-visit nursing for patients of neuronal
      intractable diseases based on PCAPS.

PMID- 19592989
TI  - Usability testing of a Falls Prevention Tool Kit for an inpatient acute care
      setting.
AB  - Efforts to prevent falls in the hospital setting involves identifying patients at
      risk of falling and implementing fall prevention strategies. This poster
      describes the method and results of Performance Usability Testing on a web-based
      Fall Prevention Tool Kit (FPTK) developed as part of a research study, (Falls
      TIPS-Tailoring Interventions for Patient Safety) funded by The Robert Wood
      Johnson Foundation.

PMID- 19592990
TI  - What does your IV smart pump infusion data tell you about IV clinical practice
      and patient safety?
AB  - Nursing in the era of ehealth integrates 'clinical systems data' in all domains
      of nursing practice to improve patient care outcomes. As clinical consultants at
      Baxter Canada, a nursing informatics approach to clinical IV data analysis was
      completed at (2) Canadian hospitals in 2008. A summary of the hospitals' clinical
      infusion data results will be outlined in relation to IV clinical practice,
      patient safety and hospital accreditation standards, as a leading practice in
      innovation. A total of 536 infusion pumps, capturing infusion starts over (3)
      days of infusion pump activity was collected. The preliminarily key infusion data
      results include: (24) Near Misses/Averted and (80) Drug Dose Overrides that
      clinicians were alerted to confirm the correct dose.

PMID- 19592991
TI  - Applying RFID systems to improve the correctness of newborn identity
      reconfirmation.
AB  - The purpose of this study is mainly lies in using the RFID technology with
      function such identifying, tracking and the repetition read-write characteristic,
      applies in the newborn newborn's identity identification, from the delivery room
      birth until to discharged from hospital. Through this system to establish,
      Improve the accuracy of drug delivery, guarantees the newborn identity
      identification effectively the safety control.

PMID- 19592993
TI  - Detection of possible medication-related errors in hypertension plans documented
      using a PDA-based APN clinical log.

PMID- 19592992
TI  - Transforming the fall-injury risk assessment tool from paper to electronic.
AB  - In order to ensure the highest possible safety for our patients, we identified a
      need to introduce a falls risk assessment tool with high sensitivity, specificity
      and reliability within our institution. A comparative research study was
      conducted which evaluated several instruments against actual patient falls. Based
      on the findings a new instrument was selected and converted to an electronic
      format compatible with existing nursing informatics systems. We are now testing
      the use of this version of the instrument for its ability to guide appropriate
      interventions that prevent falls.

PMID- 19592994
TI  - Comparison of fall rates from different resources: a self report system and an
      electronic medical record system.

PMID- 19592995
TI  - Identifying routine surge for poison control telephone response systems.

PMID- 19592996
TI  - A clinical-decision support system for the nursing process in the ENR.
AB  - This study was conducted to develop the clinical-decision support system for the
      nursing process in the Electronic nursing record system. Nursing diagnoses were
      linked to 4 components of the nursing process (except for diagnoses) and applied
      to ENR in 2007.

PMID- 19592998
TI  - Five elements of music therapy research on the influence of emotion and meridian.
AB  - 70% to 90% diseases are caused from mixture of emotions and sensory pleasures and
      pressure. To contemporary people, the pressure is omnipresent. According to World
      Health Organization (WHO) recognizing, there are more than 80 types of physical
      and psychological diseases, most of them are related to psychology. In recent
      years more and more people believe and research on music therapy.

PMID- 19592997
TI  - Nursing informatics implications from a study of unmet nursing care needs.
AB  - A number of issues related to data collection and analysis have impeded
      researchers from documenting a process of nursing care-outcome link. While health
      services research (HSR) continues to develop and test novel research methods to
      better understand the quality paradigm there has been steady progress in
      informatics research to represent, acquire, and store nursing data. The use of
      HSR methods may provide empirical and theoretical support for nursing informatics
      research. Moreover, large clinical datasets that include standardized nursing
      data provide an important basis for HSR.

PMID- 19592999
TI  - Content and functional assessment of a HIV/AIDS tailored web-based symptom self
      assessment and self management tool.

PMID- 19593001
TI  - Development of educational software for teaching nursing management.
AB  - In Brazil, the first experiences using informatics in nursing education was in
      1985. In spite of the time, this area still continues lacking in relation to
      initiatives using the computer as a pedagogic instrument. This study aim to
      demonstrate the development of an educational software for teaching nursing
      management using interactive multimedia. The methodology was based in the three
      stages Model for development of CAI system. The software was developed in four
      modules using the Macromedia Authorware Professional v.7. As conclusion, the
      educational software was well accepted by the faculty members, emerging positive
      comments on the developed product. The texts, graphs, sound and images favoring
      the teach-learning process. Since the educational software is developed for
      educating nursing students, the next step will be to sample students to measure
      their satisfaction.

PMID- 19593004
TI  - Nationwide survey on the introduction of nursing diagnosis at nursing schools in
      Japan.
AB  - We conducted a nationwide survey to grasp the current status of the introduction
      of nursing diagnosis at nursing schools. This survey showed that there was a gap
      in awareness between hospitals [1], which require nursing diagnosis skills, and
      nursing schools, more than half of which do not teach nursing diagnosis. The
      survey thus demonstrated the importance of collaborations and information sharing
      in nursing education.

PMID- 19593005
TI  - Efficiency of blended e-learning classes using nursing practice example.
AB  - We are developing a nursing education system utilizing e-learning. The objective
      of the study project we conducted and are describing herein is to show how
      efficient e-learning is when applied for nursing education along with ordinary
      face-to-face teaching classes held in parallel. We call this instruction mode
      blended e-learning. This paper reports the efficiency of such an education method
      based on a survey of the evaluations produced by students who actually attended e
      learning classes in 2007.

PMID- 19593006
TI  - Identification of subject areas in nursing informatics for the nursing manager
      curriculum.
AB  - To be able to adequately provide nursing informatics education to nursing
      managers working at Japanese hospitals, areas in which there is an urgent need
      for education in information-related ability were decided using the Delphi method
      based on a survey of nursing informatics experts. The experts participating in
      the survey were lecturers responsible for teaching information-related subjects
      in the nursing manager curriculum accredited by the Japanese Nursing Association.
      Among the 26 subjects that were selected, those related to informatics knowledge
      and skills exceeded those related to computer skills.

PMID- 19593007
TI  - Developing competences and use of the Finnish model of documentation of nursing
      care - R&D project eNNI.
AB  - Electronic documentation of nursing care is going to be realized in Finland with
      FINCC and using a coherent model. The research and development project for
      creation of competences needed in the country is financed by the Ministry of
      Education and the partners are 14 universities of applied sciences (UAS).

PMID- 19593008
TI  - Caregivers' knowledge and skills: which reality?
AB  - The study is taking place in the Orthopaedic ward in Matosinhos Local Health Care
      Unit and its aim is to assess informal caregivers' knowledge and skills in the
      case of patients dependent in self-care. The information is being gathered
      through an interview with closed questions to sixty caregivers at the time of
      discharge concerning existing knowledge and skills; a second interview is then
      carried out later during the first nursing appointment in the hospital, only this
      time concerning information sources that the caregivers used to address deficits
      in knowledge and skills shown at the time of discharge.

PMID- 19593009
TI  - Teaching undergraduate nursing students renal care in a 3D Gaming Environment.
AB  - The original program on renal care was developed between 1995-1997 using
      'Toolbook' software, which presented the content in a non interactive graphical
      way without tracking student progress or recording of results and was available
      to students via a CDRom. The content described the clinical decision making
      process that practitioners had to follow when diagnosing and managing renal
      diseases. These processes followed a learning sequence whereby a series of
      decisions lead to the next phase of the diagnosis and treatment. The purpose was
      to simulate the live clinical decision making processes for practitioners. An
      additional build-in 'Ask the Expert'-button (Help function) guided students in
      correct clinical decision making. One of the problems encountered in the original
      program is that the navigation is not intuitive to the user and students could
      get easily lost while going through the step-by-step introduction as well as the
      lack of interactivity. The original program still has relevant learning content,
      but the software, illustrations and tracking of learning outcomes are out-of
      date. Therefore a re-design of the original program using a 3D Gaming Environment
      with updated content is being undertaken. This paper will discuss the methodology
      underpinning the new development, a demonstration of the program and the results
      from student feedback which will be undertaken in February - March 2009.

PMID- 19593010
TI  - Interactive eLearning - a safe place to practice.
AB  - Interactive web-based learning environment offers refreshing opportunities to
      create innovative solutions to explore and exploit informatics support on-the-job
      training. We report from a study where a hospital is created a interactive
      eLearning resource. The modules are creating a safe place to practice - to be
      used for introduction to the work and preparation for certification or re
      certification of competencies.

PMID- 19593011
TI  - Is computer assisted learning among nurses or nursing students more effective
      than traditional learning? - A mini-review.

PMID- 19593012
TI  - Second life: not your conventional simulation.
AB  - Second Life is a massive, multiuser, virtual environment. The University of
      Kansas School of Nursing has introduced SL into the health informatics curriculum
      as a virtual environment for students and faculty to interact and communicate.
      Students have successfully completed course activities in SL. Informatics faculty
      continue to develop simulations in SL.

PMID- 19593013
TI  - HOHNEU: e-learning in occupational health education.
AB  - In the scope of the EU Leonardo project we developed an online master degree
      program in occupational health. During the project we performed two studies to
      research how the on line education is perceived by prospective students and
      lecturers. They showed that e-learning is an appropriate method for occupational
      health education but to be successful we also have to take into the consideration
      that health education requires some specific requirements which must be
      fulfilled.

PMID- 19593014
TI  - Active learning in later life period.
AB  - It is well known that we are ageing more and more each day and that elderly are
      one of the most vulnerable population. Therefore we have to think globally how to
      reconnect elderly people into the active life again and to rebuild their personal
      challenges in connection with the society and in this way improve their quality
      of life. But however we have to be aware that we can not improve life of elderly
      people without improvement of their physical and mental activity.

PMID- 19593015
TI  - Development of e-learning system for patient education of diet and radiation
      safety.

PMID- 19593016
TI  - A web-based training system for elevating nursing students' risk sensitivity.
AB  - On-site training through role plays and the use of audio-visual resources has
      been effective to enhance nurses' capacity to foresee potential risks.
      Nevertheless, reports on accidents by nursing students or novice nurses continue
      to exist. This paper proposes a web-based training system as a new teaching
      strategy for elevating nursing students'risk sensitivity. It introduces two case
      studies involving possible falling risks. It consists of simulation based on
      these case studies and diagnostic tests. It is suggested this system should be
      used to examine nurses' capability of avoiding risks.

PMID- 19593017
TI  - How do patients evaluate their education? - a comparison of two education
      methods.
AB  - A Randomized controlled trial was used to compare the ambulatory orthopaedic
      surgery patients' evaluations of Internet-based education (experiment) and face
      to face education with a nurse (control). Patients in the control group evaluated
      their education to meet their needs better than patients in the experiment group.
      Both groups evaluated the education quite positively.

PMID- 19593018
TI  - Nursing informatics: scope and standards of practice.
AB  - The American Nurses Association published the third iteration of its nursing
      informatics scope and standards of practice in 2008. This work reflects the
      significant evolution of the specialty from the original scope of practice
      statement published in 1994 and the first nursing informatics standards of
      practice in 1995. Although the definition of nursing informatics remains
      essentially unchanged from that presented in 2001, the inclusion of "wisdom"
      reflects today's emerging mandate for evidence-based practice and decision
      support resources for the knowledge worker.

PMID- 19593019
TI  - Using computerized tailored questionnaires for symptom assessment and coping
      strategies evaluation in nursing research.
AB  - This presentation is to demonstrate how a ubiquitous database program (Microsoft
      Access) was utilized to collect data when individuals' symptoms, and the self
      care strategies they implemented, changed on a week to week basis.

PMID- 19593020
TI  - Standardized nursing documentation - developing together.
AB  - The law of electronic patient' documentation came into operation in Finland in
      June 2007. The law obligates organizations of health care to connect with
      national information service system before 2011. According to definitions
      electronic patient record should be uniform and structured. Unified
      classification, terminology and core data elements will be used in the
      documentation of nursing care plan. This requires new knowledge and the movement
      towards to plan the education of nursing informatics. eNNi-project is focusing on
      the research and development of the transition of the education of documentation.

PMID- 19593023
TI  - Education for Japanese informatics nurses.
AB  - We compared the certification system for Healthcare Information Technologists
      (HITs) with that for Informatics Nurses (INs). HITs lacked only two items. If
      these items could be made part of graduate education, it would be possible to use
      the HITs certification as a basic part of the qualification, and develop a
      graduate program for Japanese INs.

PMID- 19593021
TI  - Reducing health disparities and improving patient safety and quality by
      integrating HIT into the Columbia APN curriculum.

PMID- 19593025
TI  - Nursing informatics in Sweden - the agenda for the future.
AB  - With the purpose of getting an overview of the current research and development
      in information systems and terminology for nursing practice and outline
      strategies for the future, an initiative for a workshop was taken at the national
      level in Sweden by the Section for Nursing Informatics, the Society of Nursing
      and the Association of Health Professionals in 2007. For the workshop around 30
      nurses were invited, representing clinical practice, education, and research. The
      workshop resulted in recommendations for future strategies to support the
      development of nursing informatics in Sweden.

PMID- 19593026
TI  - Nurse informaticians in Finland - who are they and what are they doing?
AB  - The role of a nurse informatician is not yet common in health care settings in
      Finland although electronic patient records have been in use since 1980's. A web
      based survey instrument was compiled based on the surveys conducted by HIMSS in
      spring 2009. The aim was to find out what kind of positions nurses have in
      nursing informatics in the Finnish health care sector. Based on the results the
      role of nurse informaticians varied between hospitals and health centres based on
      organization size and affiliation weather on IT-department or clinical setting.
      In many organizations nurses are also working quite isolated due to scarce number
      of nurses in the field of informatics.

PMID- 19593027
TI  - Using change theory to examine the nursing informatics development in Taiwan.
AB  - The purpose of this study is to apply Kurt Lewin's change theory to examine the
      nursing informatics development in Taiwan. The first stage, Unfreezing, is using
      Excel VBA training program to educate the nurses; the second stage, Change, is
      establishing the "Taiwan Nursing Informatics Association (TNIA)"; in the final
      stage, Refreezing, we are still working on new strategies to promote the NI
      nationwide. The recent challenge of nursing informatics in Taiwan is lack of
      programs to introduce the NI more systematically and thoroughly.

PMID- 19593028
TI  - Development opportunities for nursing.
AB  - Factors which ensure correct functioning of health services are quantity and
      quality of medical personnel, including nurses whose roles are specific. No one
      but nurses are largely responsible not only for the quality of medical services
      in a given country, this phenomenon being especially noticeable in the developed
      countries, but also directly or indirectly for approximately 70% of expenditures
      in health services.

PMID- 19593029
TI  - The quality report of national ever-awarded health websites in Taiwan.
AB  - The Ministry of Health in Taiwan has promoted the award campaign to assure the
      health web information since 2002. The 98 ever-awarded web sites were reexamined
      with the new set of quality indicators in 2007. The results show that the overall
      quality only at an acceptance level and much work needs to be done in credibility
      and site interaction.

PMID- 19593031
TI  - Developing a visualized patient-centered, flow-based and objective-oriented care
      path of cardiac catheterization examination.
AB  - It has been known that visualization is a user-preferred and more meaningful
      interface of information systems. To reduce the anxiety and uncertainty of
      patients, we transformed the sophisticated process of cardiac catheterization
      into visualized information. The Microsoft Visio 2003 and Excel 2003 with the VBA
      automation tool were used to design a process flow of Cardiac Catheterization.
      The results show the technical feasibility and potentials helpful for patient to
      realize the nursing process of cardiac catheterization.

PMID- 19593030
TI  - Clinical decision support systems to prevent and treat pressure ulcers and under
      nutrition in nursing homes.
AB  - Clinical decision support systems (CDSSs) are believed to have the potential to
      improve care and change the behavior of health personnel. The project has focused
      on developing a CDSS to support prevention of pressure ulcer and undernutrition
      that is completely integrated in the electronic health record in nursing homes.
      Nursing staff have been involved in all phases in the development of the CDSS,
      which at present is ready to be implemented and systematically evaluated.

PMID- 19593032
TI  - What is the out-patient nurse thinking-from hand-written to information system
      uses.
AB  - Information systems auxiliary lot of nursing activities, what is nurse thinking
      about that information system for work; compared to the period of hand-written
      what are the differences between them? How was the situation that nurse work
      across the era from hand-written to information system uses? Use in-depth
      interview study of the phenomenological approach, then summarizing by Collaizzi
      phenomenological analysis, to know the nurse how to cross working style change,
      help hospital implement new technology in the future could be more smoothly into
      the situation, effectively reducing the operating costs.

PMID- 19593033
TI  - Who attended the NI training programs in Taiwan?
AB  - We promoted the Nursing Informatics since 2002 and started to hold a variety of
      NI training programs and workshops since 2003. In the period of 2003-2006 more
      than 310 participants have attended 24 training programs. The majority of
      attendants were from clinical settings, especially medical centers, and from
      northern Taiwan in which healthcare resources are more sufficient. We observed
      the needs in clinical settings and imbalanced distribution of HIS resources.

PMID- 19593034
TI  - The effect of a standardized form in guiding communication between peers during
      the hand-off of patients in a hospital setting.
AB  - The Joint Commission, whose mission is to continuously improve the safety and
      quality of care provided to the public through health care organizations
      establishes annual National Patient Safety Goals as part of their accreditation
      process of hospitals in the United States. One of the stated goals for 2009 is to
      improve the effectiveness of communication among caregivers. Hospitals, in
      meeting this goal, have used various methods, including the development of hand
      off standards and improvements to supporting information systems.

PMID- 19593035
TI  - Peer support from online community on the internet among patients with breast
      cancer in Japan.
AB  - This study describes the current status of peer support through an online
      community among patients with breast cancer, and examines how the support differs
      through the patients' usage of the community. Self-reported questionnaires
      distributed to 465 patients through Internet were analyzed. Analysis indicated
      the peer support among patients was categorized according to the following 5
      factors: "emotional support, helper-therapy," "emotional expression," "conflict,"
      "advice," and "insight, universality." Even the patients who only read the
      postings of other patients received benefits from the community.

PMID- 19593036
TI  - Structuring development process of learning knowledge and procedure in healthcare
      using the unit process flow chart.
AB  - Websites are effective in supplying knowledge and learning methods in healthcare
      and also in improving them. However, either a supplier of the knowledge or a
      supplier of the learning method based on the knowledge is not able to accumulate
      what they have learnt through the development. We developed a system to improve
      development processes of knowledge and of learning method by using the
      methodology of quality management. In the development, we introduced a concept of
      Unit Process and used the 'Unit Process Flow Chart' in order to structure a
      process.

PMID- 19593037
TI  - End-user developed workflow-based hemodialysis nursing record system.
AB  - We reported how we decided to build our own Hemodialysis nursing record system
      using the end user computing strategy with Excel VBA. The project took one year
      to complete since we used our off-duty time and started everything from the
      grounds. We are proud of the final system which tightly meets our workflow and
      clinical needs. Its interface was carefully designed to be easy to use with a
      style.

PMID- 19593038
TI  - Visualizing simulated learning experiences through the use of informatics tools.
AB  - High-fidelity simulation technology is a growing educational technology.
      Designing effective simulations requires the use of informatics tools such as UML
      modeling. This poster demonstrates the steps in modeling a simulation exercise.

PMID- 19593039
TI  - DockFlow - a prototypic PharmaGrid for virtual screening integrating four
      different docking tools.
AB  - In this paper we present DockFlow, a prototypic version of a PharmaGrid. DockFlow
      is supporting pharmaceutical research through enabling virtual screening on the
      Grid. The system was developed in the course of the BRIDGE project funded by the
      European Commission. Grids have been used before to run compute- and data
      intensive virtual screening experiments, like in the WISDOM project. With
      DockFlow, however, we addressed a variety of problems yet unsolved, like the
      diversity of results produced by different docking tools. We also addressed the
      problem of analysing the data produced in a distributed virtual screening system
      applying a combinatorial docking approach. In DockFlow we worked on a grid-based
      problem solving environment for virtual screening with the following major
      features: execution of four different docking services (FlexX, AutoDock, DOCK and
      GAsDock) at locations in Europe and China remotely from a common workflow,
      storage of the results in a common Docking Database providing a shared analysis
      platform for the collaboration partners and combination of the results. The
      DockFlow prototype is evaluated on two scientific case studies: malaria and avian
      flu.

PMID- 19593040
TI  - Running medical image analysis on GridFactory desktop grid.
AB  - At the Geneva University Hospitals work is in progress to establish a computing
      facility for medical image analysis, potentially using several hundreds of
      desktop computers. Typically, hospitals do not have a computer infrastructure
      dedicated to research, nor can the data leave the hospital network for the
      reasons of privacy. For this purpose, a novel batch system called GridFactory has
      been tested along-side with the well-known batch system Condor. GridFactory's
      main benefits, compared to other batch systems, lie in its virtualization support
      and firewall friendliness. The tests involved running visual feature extraction
      from 50,000 anonymized medical images on a small local grid of 20 desktop
      computers. A comparisons with a Condor based batch system in the same computers
      is then presented. The performance of GridFactory is found satisfactory.

PMID- 19593041
TI  - Application of Grid technology for automated detection of sleep disordered
      breathing.
AB  - Sleep related breathing disorders (SRBD) represent a major disease in sleep
      medicine. For diagnosis and therapy control, extensive overnight investigations
      are required, encompassing long-term measurement of multiple biosignals in
      specialized sleep disorders centers. To date, evaluation of the examination is
      realized by comprehensive visual inspection of the data by an expert. Therefore,
      many approaches have been made to facilitate diagnosis, among them automated
      analysis of the ECG signal. In this article, we present a grid based
      infrastructure for computer aided diagnosis of SRBD, accessible for distributed
      users. As the analysis algorithms itself are still in a validation phase, and the
      Grid infrastructure is not approved for clinical applications, the application is
      currently used for research purposes only. But as important aspects of data
      security, accessibility from protected environments, usability and fault
      tolerance are already covered, the implementation is a solid base for further
      enhancement of the platform and paves the way for a sustainable service grid for
      sleep medicine.

PMID- 19593042
TI  - Towards production-level cardiac image analysis with grids.
AB  - Production exploitation of cardiac image analysis tools is hampered by the lack
      of proper IT infrastructure in health institutions, the non trivial integration
      of heterogeneous codes in coherent analysis procedures, and the need to achieve
      complete automation of these methods. HealthGrids are promising technologies to
      address these difficulties. This paper details how they can be complemented by
      high level problem solving environments such as workflow managers to improve the
      performance of applications both in terms of execution time and robustness of
      results. Two of the most important important cardiac image analysis tasks are
      considered, namely myocardium segmentation and motion estimation in a 4D
      sequence. Results are shown on the corresponding pipelines, using two different
      execution environments on the EGEE grid production infrastructure.

PMID- 19593043
TI  - An Easy Setup for Parallel Medical Image Processing: Using Taverna and ARC.
AB  - Medical image processing is known as a computationally expensive and data
      intensive domain. It is thus well-suited for Grid computing. However, Grid
      computing usually requires the applications to be designed for parallel
      processing, which is a challenge for medical imaging researchers in hospitals
      that are most often not used to this. Making parallel programming methods easier
      to apply can promote Grid technologies in clinical environments. Readily
      available, functional tools with an intuitive interface are required to really
      promote healthgrids. Moreover, the tools need to be well integrated with the Grid
      infrastructure. To facilitate the adoption of Grids in the Geneva University
      Hospitals we have set up a develop environment based on the Taverna workflow
      engine. Its usage with a medical imaging application on the hospitals' internal
      Grid cluster is presented in this paper.

PMID- 19593045
TI  - Crossing Healthgrid borders: early results in medical imaging.
AB  - Image analysis has been strongly present in several healthgrid initiatives from
      the start, and today we find many imaging projects with successful grid
      implementations and developments. An example is the analysis of functional MRI
      data on grids, which has been successfully realized by several projects and that
      could be of interest for others. However, crossing the borders of existing grids
      is not trivial because the infrastructures being created for these projects
      differ, each adopting a (slightly) different software stack. This paper describes
      our early attempts to cross the borders between the German and Dutch grid
      infrastructures for medical imaging, motivated by a true wish to share expertise
      about fMRI analysis on grids between these two communities. We describe how we
      used off-the-shelf, production-level, grid technology to implement supporting
      mechanisms for cooperation in fMRI at several levels (users, data, software,
      workflows and computing resources). This simple exercise provided us valuable
      insights into the problems of crossing the borders of real grids from a user's
      perspective. Besides technical aspects, we observed that security and usability
      are very important for the success of inter-operation of Healthgrid.

PMID- 19593044
TI  - A collaborative environment allowing clinical investigations on integrated
      biomedical databases.
AB  - In order to perform clinical investigations on integrated biomedical data sets
      and to predict virological and epidemiological outcome, medical experts require
      an IT-based collaborative environment that provides them a user-friendly space
      for building and executing their complex studies and workflows on largely
      available and high-quality data repositories. In this paper, the authors
      introduce such a novel collaborative working environment a so-called virtual
      laboratory for clinicians and medical researchers, which allows users to
      interactively access and browse several biomedical research databases and re-use
      relevant data sets within own designed experiments. Firstly, technical details on
      the integration of relevant data resources into the virtual laboratory
      infrastructure and specifically developed user interfaces are briefly explained.
      The second part describes research possibilities for medical scientists including
      potential application fields and benefits as using the virtual laboratory
      functionalities for a particular exemplary study.

PMID- 19593046
TI  - Enabling of grid based diffusion tensor imaging using a workflow implementation
      of FSL.
AB  - Tensor analysis of diffusion weighted magnetic resonance images is increasingly
      used for non-invasive tracking of nerve fibers in the human brain. Diffusion
      tensor imaging (DTI) enables in-vivo research on the internal structure of the
      central nervous system, encompassing interconnection of functional areas,
      correlation between fiber deformations and certain disease patterns, as well as
      brain tumor localization. But the modeling of the local diffusion parameters is a
      computationally expensive part of the processing pipeline, resulting to run times
      up to days on standard desktop computers. A grid implementation of the algorithm
      with slice based parallelization reduces the processing down to 10% compared to a
      local cluster and 20% compared to sequential processing on the grid. A workflow
      implementation enables fault-tolerant handling of temporary failures within the
      grid. Furthermore, pure web-based access to the grid application allows for
      collaborative utilization even from protected infrastructures, as they are
      typically found in clinical environments.

PMID- 19593047
TI  - Grid computing for detailed hemodynamics-simulation-based planning of
      endovascular interventions.
AB  - Detailed numerical simulations of blood flow in arteries with various
      malformations and its conjugate loads on the vessel walls have been a research
      topic for specialized medical and engineering communities over decades. The
      present state of computing resources and software allows access to these
      elaborate diagnostic and research tools to a broad user circle and even to
      integrate them into clinical workflows. To tap the full potential of hemodynamic
      simulations, a Grid-based "virtual vessel surgery" application has been developed
      and deployed as part of the image processing module of the MediGRID project of
      the German Federal Ministry of Education and Science (BMBF). The very resource
      intensive parts of that application, including not only the numerical simulation
      itself, but also automated data pre- and post-processing and visualization are
      implemented and are made available through the MediGRID portal. Some highly
      interactive workflow steps of the application are left at the user site but
      automated - via a specially developed Web interface - to a degree allowing
      intuitive, fast interaction and seamless integration with the Grid components.
      Standard middleware provided by D-Grid is used throughout. The complete workflow
      is implemented into the grid and can in principle be carried out using no
      external software. It was applied to real vessel data with a stenosis and an
      aneurysm, respectively.

PMID- 19593048
TI  - Metadata extraction using text mining.
AB  - Grid technologies have proven to be very successful in the area of eScience, and
      healthcare in particular, because they allow to easily combine proven solutions
      for data querying, integration, and analysis into a secure, scalable framework.
      In order to integrate the services that implement these solutions into a given
      Grid architecture, some metadata is required, for example information about the
      low-level access to these services, security information, and some documentation
      for the user. In this paper, we investigate how relevant metadata can be
      extracted from a semi-structured textual documentation of the algorithm that is
      underlying the service, by the use of text mining methods. In particular, we
      investigate the semi-automatic conversion of functions of the statistical
      environment R into Grid services as implemented by the GridR tool by the
      generation of appropriate metadata.

PMID- 19593049
TI  - The GLOBE 3D Genome Platform - towards a novel system-biological paper tool to
      integrate the huge complexity of genome organization and function.
AB  - Genomes are tremendous co-evolutionary holistic systems for molecular storage,
      processing and fabrication of information. Their system-biological complexity
      remains, however, still largely mysterious, despite immense sequencing
      achievements and huge advances in the understanding of the general sequential,
      three-dimensional and regulatory organization. Here, we present the GLOBE 3D
      Genome Platform a completely novel grid based virtual "paper" tool and in fact
      the first system-biological genome browser integrating the holistic complexity of
      genomes in a single easy comprehensible platform: Based on a detailed study of
      biophysical and IT requirements, every architectural level from sequence to
      morphology of one or several genomes can be approached in a real and in a
      symbolic representation simultaneously and navigated by continuous scale-free
      zooming within a unique three-dimensional OpenGL and grid driven environment. In
      principle an unlimited number of multi-dimensional data sets can be visualized,
      customized in terms of arrangement, shape, colour, and texture etc. as well as
      accessed and annotated individually or in groups using internal or external data
      bases/facilities. Any information can be searched and correlated by importing or
      calculating simple relations in real-time using grid resources. A general
      correlation and application platform for more complex correlative analysis and a
      front-end for system-biological simulations both using again the huge
      capabilities of grid infrastructures is currently under development. Hence, the
      GLOBE 3D Genome Platform is an example of a grid based approach towards a virtual
      desktop for genomic work combining the three fundamental distributed resources:
      i) visual data representation, ii) data access and management, and iii) data
      analysis and creation. Thus, the GLOBE 3D Genome Platform is the novel system
      biology oriented information system urgently needed to access, present, annotate,
      and to simulate the holistic genome complexity in a unique gateway towards a real
      understanding, educative presentation and curative manipulation planning of this
      tremendous evolutionary information grail - genomes.

PMID- 19593050
TI  - Using grid-enabled distributed metadata database to index DICOM-SR.
AB  - Integrating medical data at inter-centre level implies many challenges that are
      being tackled from many disciplines and technologies. Medical informatics have
      applied an important effort on describing and standardizing Electronic Health
      Records, and specially standardisation has achieved an important extent on
      Medical Imaging. Grid technologies have been extensively used to deal with multi
      domain authorisation issues and to provide single access points for accessing
      DICOM Medical Images, enabling the access and processing to large repositories of
      data. However, this approach introduces the challenge of efficiently organising
      data according to their relevance and interest, in which the medical report is a
      key factor. The present work shows an approach to efficiently code radiology
      reports to enable the multi-centre federation of data resources. This approach
      follows the tree-like structure of DICOM-SR reports in a self-organising metadata
      catalogue based on AMGA. This approach enables federating different but
      compatible distributed repositories, automatically reconfiguring the database
      structure, and preserving the autonomy of each centre in defining the template.
      Tools developed so far and some performance results are provided to prove the
      effectiveness of the approach.

PMID- 19593051
TI  - XTENS - an eXTensible environment for neuroscience.
AB  - The XTENS (eXTensible Environment for NeuroScience) platform consists in an
      highly extensible environment for collaborative work that improve repeatability
      of experiment and provides data storage and analysis capabilities. The platform
      is divided in repository and application domains, branched in services with
      different purpose. The first domain is the central component of the platform and
      consists in a multimodal repository with a client-server architecture. The second
      one provides remote tools for image and signal visualization and analysis. The
      main issue for such a platform is not only to provide an extensible collaborative
      environment, but also to build a development platform for testing models and
      algorithms in neuroscience. For these reasons a Grid approach has been
      considered. Both computational and data Grids infrastructures can be exploited to
      analyze and share large datasets of distributed data. The architecture has been
      deployed to support surgical planning for patients affected by drug resistant
      epilepsy. In that scenario, a complex analysis for a fully multimodal dataset
      including different image modalities, EEG and video is required to localize the
      origin of the ictal discharge and critical brain areas. As first results,
      prototype versions of both repository and application domain components are
      presented.

PMID- 19593052
TI  - Preserving consent-for-consent with feasibility-assessment and recruitment in
      clinical studies: FARSITE architecture.
AB  - Best practice guidance for clinical studies asks investigators to employ the
      highest possible standards in privacy and consent. When considering the
      feasibility of a clinical study, issues of privacy extend not only to actual but
      also to potential study participants. The consent required to access records to
      determine whether or not an individual might be eligible to participate in a
      study is sometimes referred to as consent-for-consent. Some initiatives to
      enhance the efficiency of study-recruitment could compromise consent-for-consent,
      for example by inviting a patient to take part in a study without the knowledge
      of their attending clinician. Through iterative working with experts and
      examination of protocols we explored a range of scenarios for assessing the
      feasibility of clinical trials and observational studies, and recruiting
      participants. The main requirement we identified was to speed up feasibility
      assessment and recruitment while preserving the patient-clinician trust
      relationship that is central to consent-for-consent. We present an appropriate
      information system architecture, FARSITE (Feasibility Assessment and Recruitment
      System for Improving Trial Efficiency), and show in principle that faster
      recruitment into clinical studies need not compromise best practice in privacy or
      consent. We show that FARSITE is a specific instance of an 'e-Lab' architecture
      for assembling data, methods and expertise around study protocols and defined
      populations.

PMID- 19593053
TI  - Economic performance and sustainability of HealthGrids: evidence from two case
      studies.
AB  - Financial sustainability is not a driving force of HealthGrids today, as a
      previous desk research survey of 22 international HealthGrid projects has showed.
      The majority of applications are project based, which puts a time limit of
      funding, but also of goals and objectives. Given this situation, we analysed two
      initiatives, WISDOM and MammoGrid from an economic, cost-benefit perspective, and
      evaluated the potential for these initiatives to be brought to market as self
      financing, sustainable services. We conclude that the topic of HealthGrids should
      be pursued further because of the substantial potential for net gains to society
      at large. The most significant hurdle to sustainability - the discrepancy between
      social benefits and private incentives - can be solved by sound business models.

PMID- 19593054
TI  - Business aspects and sustainability for healthgrids - an expert survey.
AB  - Grid computing initiatives in medicine and life sciences are under pressure to
      prove their sustainability. While some first business model frameworks were
      outlined, few practical experiences were considered. This gap has been narrowed
      by an international survey of 33 grid computing experts with biomedical and non
      biomedical background on business aspects. The experts surveyed were cautiously
      optimistic about a sustainable implementation of grid computing within a mid term
      timeline. They identified marketable application areas, stated the underlying
      value proposition, outlined trends and specify critical success factors. From a
      general perspective of their answers, they provided a stable basis for a road map
      of sustainable grid computing solutions for medicine and life sciences.

PMID- 19593055
TI  - Perspectives of MediGRID.
AB  - Sustainability is a top priority for nearly all grid communities. The German grid
      communities in the area of life sciences are continuing their dissemination
      efforts in order to bring the grid to scientists. With cloud computing another
      concept for distributed IT infrastructures is on the rise. In this regard the
      grid has a different focus and matches better with life science compute power
      demands. A comparison of both grid and cloud in addition to the background and
      present status of the German life science grid give a contemporary impression of
      the future perspectives of MediGRID.

PMID- 19593056
TI  - Ontology-based privacy compliance on European healthgrid domains.
AB  - The harmonization of data protection law in Europe has been theoretically
      achieved by means of the EU directive on data protection [1]. In practice the
      harmonization is not absolute and conflicts continue to exist on the ways member
      states are implementing the directive. The integration of different European
      medical systems by means of grid technologies will continue to be challenging if
      technology does not intervene to enhance interoperability between national
      regulatory frameworks on data protection. In this paper we present an approach to
      automate privacy requirements for the sharing of patient data across Europe on a
      healthgrid [2] domain and ensure its enforcement internally and within external
      domains where the data might travel. This approach is based on the semantic
      modelling of privacy obligations that are of legal, ethical or cultural nature.
      These requirements are for the sharing of personal data between different
      European member states. Our model reflects both similarities and conflicts, if
      any, between the different member states. This will allow us to reason on the
      safeguards a data controller should ask from an organization belonging to another
      member state before disclosing medical data to them. The system will also
      generate the relevant set of policies to be enforced at the process level of the
      grid to ensure privacy compliance before allowing access to the data.

PMID- 19593057
TI  - Variance analysis as practice-based evidence.
AB  - Integrated care pathways, a fine-grained form of medical guideline including the
      explicit recording of any deviation, or 'variance', have been perceived by some
      as overly prescriptive, limiting clinical freedom and promoting 'cookbook
      medicine'. However, feeding the results of the analysis of variance back into the
      development of a pathway could be an effective way of capturing evidence from
      practice. This paper summarizes research into the development and use of ICPs,
      and includes some initial findings from a qualitative study involving clinicians
      that have helped develop or have used ICPs professionally.

PMID- 19593058
TI  - Semantic security: specification and enforcement of semantic policies for
      security-driven collaborations.
AB  - Collaborative research can often have demands on finer-grained security that go
      beyond the authentication-only paradigm as typified by many e-Infrastructure/Grid
      based solutions. Supporting finer-grained access control is often essential for
      domains where the specification and subsequent enforcement of authorization
      policies is needed. The clinical domain is one area in particular where this is
      so. However it is the case that existing security authorization solutions are
      fragile, inflexible and difficult to establish and maintain. As a result they
      often do not meet the needs of real world collaborations where robustness and
      flexibility of policy specification and enforcement, and ease of maintenance are
      essential. In this paper we present results of the JISC funded Advanced Grid
      Authorisation through Semantic Technologies (AGAST) project
      (www.nesc.ac.uk/hub/projects/agast) and show how semantic-based approaches to
      security policy specification and enforcement can address many of the limitations
      with existing security solutions. These are demonstrated into the clinical trials
      domain through the MRC funded Virtual Organisations for Trials and
      Epidemiological Studies (VOTES) project (www.nesc.ac.uk/hub/projects/votes) and
      the epidemiological domain through the JISC funded SeeGEO project
      (www.nesc.ac.uk/hub/projects/seegeo).

PMID- 19593059
TI  - A robust framework for rapid deployment of a virtual screening laboratory.
AB  - A high throughput framework for virtual screening (VS) applications has been
      designed which enables researchers in in-silico drug discovery to deploy large
      scale time-consuming virtual screening experiments on High Performance/Grid
      computing environments. Issues related to enabling virtual screening on grids
      have been addressed extensively in the past; in this paper we describe a new
      framework, which supports the rapid deployment of virtual screening services
      based on UNICORE-6 and Meta Scheduling Service (MSS). We demonstrate, how the
      deployment of complex virtual screening workflows is facilitated by this
      framework and we provide some first results of the virtual laboratory testbed
      established in the course of the EU project PHOSPHORUS. The flexibility of the
      new VS framework allows easy deployment and integration of new resources and
      applications, making the Grid more accessible to the users.

PMID- 19593060
TI  - Service engineering for grid services in medicine and life science.
AB  - Clearly defined services with appropriate business models are necessary in order
      to exploit the benefit of grid computing for industrial and academic users in
      medicine and life sciences. In the project Services@MediGRID the service
      engineering approach is used to develop those clearly defined grid services and
      to provide sustainable business models for their usage.

PMID- 19593061
TI  - Shared genomics: high performance computing for distributed insights in genomic
      medical research.
AB  - The study of the genetics of diseases is entering a new era. Increasingly, genome
      wide association studies are being used to identify positions within the human
      genome that have a link with a disease condition. The number of genomic locations
      studied means that High Performance Computing (HPC) solutions will have to
      increasingly be used in the statistical analysis of these data sets.
      Understanding the biomedical implications of the statistical analysis will also
      require heavy use of bioinformatics annotation tools. In this paper we report the
      outcome of developing HPC statistical genetics analysis codes for use by clinical
      researchers. Statistical results are automatically annotated with relevant
      biological information by calling multiple web-services orchestrated via pre
      existing scientific workflows. Access to the HPC codes and bioinformatics
      annotation processes is via a client Workbench which hides as much as possible
      from the user the HPC infrastructure and bioinformatics annotation processes,
      whilst aiding the exchange of ideas and results between stakeholders.

PMID- 19593062
TI  - The evolution of HPV by means of a phylogenetic study.
AB  - In this work we demonstrate the adequacy of revising the classification systems
      based on molecular phylogenetic calculations by allowing an arbitrary number of
      taxas that take advantage of high performance computing platforms for the Human
      papillomavirus (HPV) case. To do so, we have analysed several phylogenetic trees
      which have been calculated with the PhyloGrid tool, a workflow developed in the
      framework of the EELA-2 Project.

PMID- 19593063
TI  - Conception of an image data base for cell nuclei and geometric algorithms for
      diagnosis and therapy monitoring.
AB  - Parameters of the genome architecture of cell nuclei like copy number changes of
      genes or numerical and structural aberrations of chromosomes displayed by changes
      of size, shape, form and geometric arrangement of the related territories and
      domains play an important role in tumour diagnosis and monitoring of tumour
      therapy. We have defined data structures for such parameters, accompanied by meta
      data describing cell biology and microscopy protocols, and developed algorithms
      to deduce geometric data from microscopic raw images of fluorescently labelled
      cell nuclei. The statistical evaluation of nucleus geometry and architecture data
      is a valuable aid for diagnostic decisions and monitoring of cancer development,
      as indicated by several research case studies. The algorithms and data storage
      devices are presently administrated by different operating systems. Unification
      of workflow is being achieved for a local cluster, but gridification is still
      subject to problems of licensing, monitoring, and administering systems,
      including data security.

PMID- 19593064
TI  - A distributed security policy for neuroradiology data sharing.
AB  - Grids are key technologies to federate data distributed in multiple neuroscience
      centers, thus enabling large scale multi-centric studies. However, the take up of
      these technologies is slow due to the difficulty to manipulate sensitive
      neuroradiological data in an open environment and the recognized risk of
      federated sites to loose control over their valuable data. In this paper we
      propose a distributed data access control policy, enabling the federation of
      existing data stores, where local security policies prevail, to supports multi
      centric neuroscience studies. It achieves a compromise between enabling
      collaborative work through data sharing and preventing unauthorized access to
      data in a competitive environment.

PMID- 19593065
TI  - Medical applications for high-performance computers in SKIF-GRID network.
AB  - The paper presents a set of software services for massive mammography image
      processing by using high-performance parallel computers of SKIF-family which are
      linked into a service-oriented grid-network. An experience of a prototype system
      implementation in two medical institutions is also described.

PMID- 19593066
TI  - e-Human Grid Ecology - understanding and approaching the inverse tragedy of the
      commons in the e-Grid society.
AB  - With ever-new technologies emerging also the amount of information to be stored
      and processed is growing exponentially and is believed to be always at the limit.
      In contrast, however, huge resources are available in the IT sector alike e.g.
      the renewable energy sector, which are often even not at all used. This under
      usage bares any rational especially in the IT sector where e.g. virtualisation
      and grid approaches could be fast implemented due to the great technical and fast
      turnover opportunities. Here, we describe this obvious paradox for the first time
      as the Inverse Tragedy of the Commons, in contrast to the Classical Tragedy of
      the Commons where resources are overexploited. From this perspective the grid IT
      sector attempting to share resources for better efficiency, reveals two
      challenges leading to the heart of the paradox: i) From a macro perspective all
      grid infrastructures involve not only mere technical solutions but also
      dominantly all of the autopoietic social sub-systems ranging from religion to
      policy. ii) On the micro level the individual players and their psychology and
      risk behaviour are of major importance for acting within the macro autopoietic
      framework. Thus, the challenges of grid implementation are similar to those of
      e.g. climate protection. This is well described by the classic Human Ecology
      triangle and our extension to a rectangle: invironment-individual-society
      environment. Extension of this classical interdisciplinary field of basic and
      applied research to an e-Human Grid Ecology rational, allows the Inverse Tragedy
      of the Commons of the grid sector to be understood and approached better and
      implies obvious guidelines in the day-to-day management for grid and other
      (networked) resources, which is of importance for many fields with similar
      paradoxes as in (e-)society.

PMID- 19593067
TI  - Workflows for intelligent monitoring using proxy services.
AB  - Grid technologies have proven to be very successful in the area of eScience, and
      in particular in healthcare applications. But while the applicability of workflow
      enacting tools for biomedical research has long since been proven, the practical
      adoption into regular clinical research has some additional challenges in grid
      context. In this paper, we investigate the case of data monitoring, and how to
      seamlessly implement the step between a one-time proof-of-concept workflow and
      high-performance on-line monitoring of data streams, as exemplified by the case
      of long-running clinical trials. We will present an approach based on proxy
      services that allows executing single-run workflows repeatedly with little
      overhead.

PMID- 19593068
TI  - Reusable services from the neuGRID project for grid-based health applications.
AB  - By abstracting Grid middleware specific considerations from clinical research
      applications, re-usable services should be developed that will provide generic
      functionality aimed specifically at medical applications. In the scope of the
      neuGRID project, generic services are being designed and developed which will be
      applied to satisfy the requirements of neuroscientists. These services will bring
      together sources of data and computing elements into a single view as far as
      applications are concerned, making it possible to cope with centralised,
      distributed or hybrid data and provide native support for common medical file
      formats. Services will include querying, provenance, portal, anonymization and
      pipeline services together with a 'glueing' service for connection to Grid
      services. Thus lower-level services will hide the peculiarities of any specific
      Grid technology from upper layers, provide application independence and will
      enable the selection of 'fit-for-purpose' infrastructures. This paper outlines
      the design strategy being followed in neuGRID using the glueing and pipeline
      services as examples.

PMID- 19593069
TI  - Grid-enabled sentinel network for cancer surveillance.
AB  - Recent developments of grid services for secured distributed data management open
      new perspectives for disease surveillance. In this paper, we report on our
      initiative to develop a surveillance network for breast cancer in the Auvergne
      region. The network gathers cytopathology laboratories, structures in charge of
      cancer screening and institutes in charge of cancer epidemiology. Data stored in
      cytopathology laboratories are queried through the grid for the purpose of second
      diagnosis and to produce statistical indicators. The paper describes the network
      goal and design and discusses specific issues related to patient identification
      and security.

PMID- 19593070
TI  - Healthcare-associated infections as patient safety indicators. Notes from the
      editor-in-chief.

PMID- 19593071
TI  - Healthcare-associated infections as patient safety indicators.
AB  - Healthcare-associated infections (HAIs) are a pressing and imminent patient
      safety concern as they cause substantial preventable morbidity and mortality.
      Despite this, there is a strong tendency for healthcare administrators and
      providers to view them as far less of a threat to patient safety than adverse
      events such as medication administration errors and falls. Further, validated
      strategies to prevent HAIs are frequently slow to be adopted. This paper reviews
      two HAIs of increasing visibility and importance - namely, methicillin-resistant
      Staphylococcus aureus and Clostridium difficile - and discusses the pivotal
      importance of hand hygiene and environmental cleaning in their prevention.
      Possible reasons why HAIs are approached differently from other patient safety
      issues are discussed, including the false sense of security created by the advent
      of antibiotics, the lack of randomized controlled trials supporting infection
      control interventions and the systemic multifactorial causes of HAIs that result
      in a need for interventions that go far beyond traditional clinical boundaries.
      Suggested strategies to improve patient safety with respect to HAIs are provided,
      including a focus on the role of potential links to accreditation; the role of
      public reporting; healthcare facility design; change management strategies;
      visible leadership and role modelling; collaboration between facilities and with
      public health; reducing hospital overcrowding; and accountability and funding.
      Finally, the impact of the burgeoning interest of the media, the threat of legal
      liability and the well-being of healthcare providers are discussed.

PMID- 19593072
TI  - Healthcare-associated infections: infection prevention and control within the
      Accreditation Canada Qmentum Program.
AB  - Gardam, Lemieux, Reason, van Dijk and Goel argue that healthcare-associated
      infections (HAIs) are "a pressing and imminent concern in the context of patient
      safety." Accreditation Canada supports the position taken by these authors. The
      prevention and control of two HAIs of great concern, methicillin-resistant
      Staphylococcus aureus and Clostridium difficile, are an integral part of the
      Accreditation Canada program. A coordinated approach to combating HAIs and
      developing a culture of infection prevention and control is necessary, one that
      involves front-line healthcare professionals, senior leadership, national and
      provincial partners and the public. Since 2005, Accreditation Canada has
      increasingly strengthened the accreditation program in this area through a number
      of new strategies, including enhanced standards, required organizational
      practices, performance measures and indicators and the introduction of education
      programs. Optimizing the value of accreditation through an integrative approach
      with organizations' quality improvement programs will contribute to effectively
      combating HAIs and developing a culture of infection prevention and control.

PMID- 19593074
TI  - Infection prevention and control in the design of healthcare facilities.
AB  - The lead paper, "Healthcare-Associated Infections as Patient Safety Indicators,"
      written by Gardam, Lemieux, Reason, van Dijk and Goel, puts forward the design of
      healthcare facilities as one of many strategies to improve patient safety with
      respect to healthcare-associated infections. This commentary explores some of the
      issues in balancing infection prevention and control priorities with other needs
      and values brought to the design process. This balance is challenged not only by
      a lack of supporting evidence but also by the superficial nature in which
      infection prevention and control are often discussed within a design context. For
      the physical environment to support any patient safety initiative, the design of
      the processes must be developed in conjunction with that of the physical
      environment so that compliance can be natural and convenient. Finally,
      consideration is given to the value of documenting decision-making related to
      infection prevention and control in facility design and ongoing assessments of
      existing facilities.

PMID- 19593075
TI  - Environmental cleaning and healthcare-associated infections.
AB  - The authors of "Healthcare-Associated Infections as Patient Safety Indicators"
      correctly identify healthcare-associated infections (HAIs) as a growing problem
      with severe consequences. In contrast to most literature, their article
      acknowledges the importance of environmental cleaning. The paper presents
      credible reasons why HAIs are treated as lesser threats than other adverse
      events. It also appropriately emphasizes prevention and calls for multiple
      interventions, including reducing occupancy rates. This commentary provides
      additional evidence of the critical role of environmental cleaning and posits
      that the devaluation of cleaning and other support services lies at the heart of
      governments' and administrators' inadequate response to HAIs. Staff cuts and
      contracting out are both a motivating factor and a consequence of this
      devaluation. The commentary concludes with recommendations.

PMID- 19593076
TI  - Risky business: failure to prevent and failure to communicate.
AB  - Healthcare-associated infections (HAIs), important threats to patient safety, are
      considered differently from other adverse events. Gardam and his colleagues
      discuss several reasons for this and outline approaches that may bring about
      changes in attitudes and enhance HAI prevention. We comment on the potential
      preventability of HAIs, the need for improved communication strategies and the
      different vision of the role of infection control personnel suggested by Gardam
      et al. Recent developments in infection control structure and management and
      patient safety in Quebec are summarized.

PMID- 19593077
TI  - Advanced technologies to curb healthcare-associated infections.
AB  - The commentary was prepared in response to the manuscript "Healthcare-Associated
      Infections as Patient Safety Indicators," by Gardam, Lemieux, Reason, van Dijk
      and Goel. Healthcare-associated infections are a severe patient safety hazard.
      Current patient safety initiatives targeting increased healthcare worker hand
      hygiene to prevent some of these infections have had limited effect. This
      commentary describes recent advances in electronic sensing and computational
      power that have provided new options to increase hand hygiene compliance as a
      step toward reducing healthcare-associated infections. Smart electronics can
      provide reasoning about a healthcare worker's circumstance and prompt the worker
      to perform hand hygiene when necessary. These novel approaches in technology
      development have tremendous potential to enhance the hand hygiene of healthcare
      workers and can support the prevention of this significant problem for patients
      in our hospitals.

PMID- 19593078
TI  - Standardization as a key to quality.
AB  - The increasing attention to healthcare-associated infections is essential and
      long overdue. The authors of the lead article point out that standardization is a
      key dimension of quality. We, as healthcare providers, must leave behind the
      historical approach of "accommodating" broad clinical variation in practice,
      tolerance of low compliance in applying clear evidence that enhances outcome, and
      accommodating intransigent, colleagues who reject infection control practices. We
      know from the behavioural literature that unless an issue affects "me," buy-in is
      significantly limited; clearly, we must help each person in the chain of care
      feel an impact. There is much we can do, and each of us must demand change.

PMID- 19593079
TI  - Vertical transmission of X4-tropic and dual-tropic HIV-1 in five Ugandan mother
      infant pairs.
AB  - BACKGROUND: We previously reported the existence of CXCR4-using HIV-1 in 6-14
      week-old Ugandan infants. Whether these viruses were transmitted from the mother
      perinatally or evolved after transmission is not known. In the current study, we
      investigated the origin of the CXCR4-using viruses in these infants by comparing
      HIV-1 envelope clones from the infants to those from their mothers at or near the
      time of delivery. METHODS: Envelope clones were isolated from five Ugandan infant
      plasma samples that harbored CXCR4-using viruses, collected at the time of HIV
      diagnosis (four at birth, one at week 6), and from their mothers at delivery.
      Coreceptor usage and phylogenetic relatedness of HIV-1 populations in mother
      infant pairs were analyzed in detail using the Trofile assay and sequence
      analysis of envelope clones, respectively. RESULTS: X4-tropic clones were
      identified in two mother-infant pairs and dual-tropic clones were found in three
      pairs, either alone or in combination with R5-tropic viruses. Dual-tropic clones
      varied in their ability to infect CXCR4-expressing cells. In each mother-infant
      pair, X4-tropic or dual-tropic clones shared similar phenotypic profiles and V3
      sequence patterns; gp160 sequences of X4-tropic and dual-tropic clones from
      infants were phylogenetically indistinguishable from those of their mothers. The
      virus populations were phylogenetically homogenous in three infants and
      segregated according to coreceptor tropism in the remaining two infants.
      CONCLUSIONS: This study demonstrates that X4-tropic and dual-tropic HIV-1 can be
      transmitted from mother to infant, before, during or shortly after delivery, and
      establishes vertical transmission as an important source of CXCR4-using viruses
      in infants.

PMID- 19593081
TI  - Radiotherapy in the treatment of resectable rectal adenocarcinoma.
AB  - The goal of treatment is to cure whereas maintaining sphincter function and
      minimizing toxicity. Although the mainstay of the treatment is surgery,
      radiotherapy (RT) is used in a substantial proportion of patients depending on
      the location and extent of the tumor. The aim of this article is to discuss the
      role of RT in patients with resectable rectal adenocarcinoma. This article is a
      review of the pertinent literature. Results show that patients with T1N0
      exophytic, well to moderately differentiated, mobile tumors < or = 3 cm in
      diameter may be treated with either transanal excision or endocavitary RT. The
      probability of cure with either approach is approximately 80% to 90% and depends
      on selection criteria. The advantages of endocavitary RT are that it is an
      outpatient procedure requiring, at most, local anesthesia and is suitable for
      elderly, infirm patients. The disadvantage is that few of these treatment units
      are available. Patients who experience a local-regional recurrence may be
      surgically salvaged. Patients who undergo transanal excision and have unfavorable
      pathologic findings including equivocal or close margins, poor differentiation,
      invasion of the muscularis propria, and/or endothelial-lined space invasion have
      a high risk of local-regional recurrence after surgery alone. The addition of
      postoperative RT improves the likelihood of cure from 85% to 90%. Patients
      presenting with unfavorable tumors that are borderline resectable with a
      transanal excision may be downstaged with preoperative RT and rendered suitable
      for a wide local excision. The addition of concomitant chemotherapy probably
      enhances downstaging and may improve the likelihood of sphincter preservation.
      Patients with T3 and/or N1 rectal cancers have a relatively high probability of
      local-regional recurrence after surgery alone. Preoperative RT and postoperative
      RT combined with adjuvant chemotherapy have been shown to significantly reduce
      the risk of local-regional recurrence and improve survival. Whether preoperative
      RT alone or combined with chemotherapy is more efficacious than postoperative
      chemoradiation remains unclear. Endocavitary RT or transanal excision is suitable
      for patients with T1N0 cancers. Depending on tumor location and extent, adjuvant
      RT may improve the probability of local-regional control and survival for
      patients with locally advanced rectal adenocarcinomas.

PMID- 19593080
TI  - Performance of an immunoassay at detecting recent infection among reported HIV
      diagnoses.
AB  - INTRODUCTION: An enzyme immunoassay to detect recent HIV-1 infection (EIA-RI) of
      less than 6 months is routinely performed on diagnoses reported to the National
      HIV case surveillance in France. We assessed the performance of the EIA-RI
      infection on this country population scale by measuring its agreement with other
      indicators of time since infection that were obtained through clinical,
      biological or testing history recorded on the surveillance reporting form.
      METHODS: We used data from the National HIV case surveillance from its debut in
      March 2003 to June 2007. Infection within 6 months was defined as a negative test
      reported within 6 months prior to diagnosis. We further ascertained this
      definition by adding information about of a symptomatic primary infection or
      biological evidence of recent seroconversion. Infection established for more than
      6 months was defined when a positive test had occurred more than 6 months prior
      to the reported diagnosis. RESULTS: Time since infection could be ascertained in
      6782 of 15, 331 (44.2%) HIV diagnoses. Assay sensitivity and specificity were
      73.8 and 83.7%, respectively. Among the 1940 cases originating from Sub-Saharan
      Africa, sensitivity and specificity were 54.1 and 90.8%, respectively.
      DISCUSSION: Assessment of the performance of the EIA-RI on a large and
      heterogeneous population revealed two major findings--significant discrepancies
      in timing from infection near the 180-day cutoff, and a performance that depends
      on the geographic origin of patients. This has implications for estimating the
      assay window period and in the perspective of incidence estimation from HIV case
      surveillance.

PMID- 19593082
TI  - Solitary plasmacytoma.
AB  - PURPOSE: To analyze the outcomes of patients treated for solitary plasmacytoma
      with definitive radiotherapy (RT). MATERIAL AND METHODS: Thirty-two patients with
      solitary plasmacytoma of bone (SPB; 22 patients) and extramedullary plasmacytoma
      (EMP; 10 patients) were treated between 1963 and 2006. The median RT dose was
      around 42.7 Gy (range, 15-54 Gy) over a median of 25 fractions (range, 1-32
      fractions). No patient received adjuvant chemotherapy. Median follow-up was 10.1
      years (range, 1-33 years). Median follow-up on living patients was 7.3 years
      (range, 2.1-33 years). RESULTS: The 10-year local-control rate after RT was 87%.
      All 4 patients who developed a local recurrence had SPBs > or = 5 cm. The 10-year
      multiple myeloma-free survival rates were: SPB, 30%; EMP, 90%; and overall, 50%.
      Progression to multiple myeloma occurred at a median of 25.1 months after RT. The
      10-year overall and cause-specific survival rates were 65% and 77%, respectively.
      The 10-year cause-specific survival rate was 65% for patients with SPB versus
      100% for those with EMP (P = 0.006). CONCLUSION: Moderate dose RT results in a
      high rate of local control. Patients with SPB are more likely to progress to
      multiple myeloma, which adversely affects their survival compared with those with
      EMP.

PMID- 19593083
TI  - Phase I study of fixed dose gemcitabine plus epirubicin in patients with advanced
      solid malignancies.
AB  - OBJECTIVES: A Phase I study was initiated to investigate fixed dose rate
      gemcitabine (GEM) combined with epirubicin (EPI) given weekly or every other
      week, since, GEM given as a standard 30 minute infusion has modest activity. The
      study was designed based on the hypothesis that prolonged exposure (over 90
      minutes) may improve response rates and combination with epirubicin (EPI) is
      synergistic. METHODS: Eligible patients had measurable refractory solid
      malignancies with adequate bone marrow, renal, and liver functions. Patients
      received GEM 800, 1000, 1250 mg/m(2) over 90 minutes followed by EPI 10 or 15
      mg/m(2) as a 30 minutes infusion on days 1, 8, and 15 or days 1 and 15 of a 28
      day cycle. RESULTS: Twenty-eight patients were enrolled and 24 are evaluable for
      overall toxicities and response rate. Toxicities include neutropenia (Gr 3 of Gr
      4, 9 pts), thrombocytopenia (Gr 3 of Gr 4, 3 pts), fatigue (Gr 3 of Gr 4, 4 pts),
      and myalgia (Gr 3 of Gr 4, 1 pt). Dose limiting toxicity was grade 4 neutropenia.
      Seven patients experienced stable disease for >16 weeks and 3 patients with
      pancreatic cancer had partial responses. CONCLUSIONS: The maximum tolerated dose
      is GEM 800 mg/m(2)/EPI 10 mg/m(2) days 1, 8, 15 or GEM 1000 mg/m(2)/EPI 15
      mg/m(2) days 1, 15 given every 4 weeks. Further studies are warranted with
      targeted therapies to define the efficacy of this doublet.

PMID- 19593084
TI  - Total cystectomy versus bladder preservation therapy for locally invasive bladder
      cancer: effect of combined therapy using balloon-occluded arterial infusion of
      anticancer agent and hemodialysis with concurrent radiation.
AB  - OBJECTIVES: We tested the usefulness of balloon-occluded arterial infusion (BOAI)
      of anticancer agent (cisplatin/gemcitabine), concomitant with hemodialysis, which
      delivers an extremely high concentration of anticancer agent to the site of a
      tumor without systemic adverse effects, along with concurrent radiation [Osaka
      Medical College (OMC)-regimen] in patients with locally advanced bladder cancer.
      The results were compared with those of cystectomy. METHODS: One hundred twenty
      four patients were assigned to receive cystectomy (Gp1, n = 62) or OMC-regimen
      (Gp2, n = 62). In Gp2, patients besides undergoing complete response subsequently
      received secondary-BOAI with gemcitabine (1600 mg). RESULTS: In Gp1, 27 of 62
      patients (43.5%) suffered disease recurrence, and more than half died within 1
      year; the remainder died thereafter. The overall 5-, 10-, and 15-year survival
      rates were 53.8%, 46.0%, and 40.0%, respectively. In contrast, in Gp2, >70% of
      patients (44 of 62), especially >95% of patients with locally invasive tumors
      achieved complete response with no evidence of recurrent disease or metastasis
      after a mean follow-up of 163 (range, 32-736) weeks. At 14 years, overall
      survival was significantly improved at 79.7% (P = 0.015 vs. Gp1). Moreover,
      salvage therapy for secondary-BOAI with gemcitabine was effective in all 3
      patients with T4 tumors or lymph node involvement, who showed stable disease (SD)
      after primary therapy with CDDP. No patients suffered Grade III or more severe
      toxicities. CONCLUSION: OMC-regimen, a new strategy for patients with locally
      invasive bladder cancer, can be curative not only in patients for whom cystectomy
      is indicated, but also in patients whose condition is not amenable to curative
      treatment and for whom merely palliative treatment would otherwise seem the only
      option.

PMID- 19593085
TI  - Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic
      stem cell transplantation: a clinical review.
AB  - Allogeneic hematopoietic stem cell transplantation provides many patients, with
      hematological and malignant diseases, hope of remission and in some cases cure.
      Because the toxicities of this approach are severe, its use has been limited to
      younger healthier patients. Nonmyeloablative and reduced intensity conditioning
      regimens depend more on donor cellular immune effects and less on the cytotoxic
      effects of the conditioning regimen to eradicate the underlying disease. This
      approach is based on the induction of host tolerance to donor cells followed by
      the administration of scheduled donor T-lymphocytes infusions. Accumulated
      clinical data have been encouraging, and prospective studies are underway to
      compare this approach to conventional myeloablative allogeneic stem cell
      transplantation with regard to outcome, durability of responses, effects on the
      immune system, and the consequences of late complications such as chronic graft
      versus-host disease.

PMID- 19593086
TI  - 2009 Southern Society For Clinical Investigation presidential address:
      opportunity knocks.

PMID- 19593089
TI  - Presentation of the Southern Society for Clinical Investigation Founders' Medal
      for 2009 to Richard W. McCallum, MD.

PMID- 19593090
TI  - Southern Society for Clinical Investigation Founders' Medal acceptance.

PMID- 19593098
TI  - Nutrition and cardiovascular disease: a symposium presented at the annual
      scientific session of the Southern Society for Clinical Investigation, February
      12-14, 2009.

PMID- 19593100
TI  - Nutrient dyshomeostasis in congestive heart failure.
AB  - The clinical syndrome congestive heart failure (CHF) has its origins rooted in a
      salt-avid state mediated largely by effector hormones of the renin-angiotensin
      aldosterone system. In recent years, this cardiorenal perspective of CHF has
      taken on a broader perspective. One which focuses on a progressive systemic
      illness, whose major features include the presence of oxidative stress in diverse
      tissues and elevated circulating levels of proinflammatory cytokines coupled with
      a wasting of soft tissues and bone. Experimental studies, which simulate chronic
      renin-angiotensin-aldosterone system activation, and translational studies in
      patients with salt avidity having decompensated biventricular failure with
      hepatic and splanchnic congestion have forged a broader understanding of this
      illness and the important contribution of a dyshomeostasis of Ca2+, Mg2+, Zn2+,
      Se2+, and vitamins D, B12, and B1. Herein, we review biomarkers indicative of the
      nutrient imbalance found in CHF and raise the question of a need for a
      polynutrient supplement in the overall management of CHF.

PMID- 19593099
TI  - Neurogenic inflammation and cardiac dysfunction due to hypomagnesemia.
AB  - Hypomagnesemia continues to be a significant clinical disorder that is present in
      patients with diabetes mellitus, alcoholism, and treatment with magnesuric drugs
      (diuretics, cancer chemotherapy agents, etc.). To determine the role of magnesium
      in cardiovascular pathophysiology, we have used dietary restriction of this
      cation in animal models. This review highlights some key observations that helped
      formulate the hypothesis that release of substance P (SP) during experimental
      dietary Mg deficiency (MgD) may initiate a cascade of deleterious inflammatory,
      oxidative, and nitrosative events, which ultimately promote cardiomyopathy, in
      situ cardiac dysfunction, and myocardial intolerance to secondary stresses. SP
      acts primarily through neurokinin-1 receptors of inflammatory and endothelial
      cells, and may induce production of reactive oxygen and nitrogen species
      (superoxide anion, NO*, peroxynitrite, hydroxyl radical), leading to enhanced
      consumption of tissue antioxidants; stimulate release of inflammatory mediators;
      promote tissue adhesion molecule expression; and enhance inflammatory cell tissue
      infiltration and cardiovascular lesion formation. These SP-mediated events may
      predispose the heart to injury if faced with subsequent oxidative stressors
      (ischemia/reperfusion, certain drugs) or facilitate development of in situ
      cardiac dysfunction, especially with prolonged dietary Mg restriction.
      Significant protection against most of these MgD-mediated events has been
      observed with interventions that modulate neuronal SP release or its bioactivity,
      and with several antioxidants (vitamin E, probucol, epicaptopril, d-propranolol).
      In view of the clinical prevalence of hypomagnesemia, new treatments, beyond
      magnesium repletion, may be needed to diminish deleterious neurogenic and
      prooxidative components described in this article.

PMID- 19593101
TI  - Vitamin D and health in the 21st century: federal initiatives to advance
      research.
AB  - The role for dietary supplements for health maintenance and disease prevention is
      receiving increasingly more attention in the public media as well as in academic
      institutions and research centers. The mission of the National Institutes of
      Health Office of Dietary Supplements is to support and promote the science on the
      benefits and risks of dietary supplements. To this end, Office of Dietary
      Supplements supports a number of initiatives to advance the evidence base on
      vitamin D. These initiatives include an evidence-based review on the relationship
      of vitamin D and calcium intakes to nutrient status indicators and health
      outcomes; developing and validating analytical methods for measuring vitamin D in
      biological fluids and foods; support for continued collection of vitamin D status
      indicators through the National Health and Nutrition Examination Survey; and
      funding for National Institutes of Health grants on vitamin D and related health
      outcomes. Taken together, these programs address research gaps and needs to
      further the science and exploration of the role of vitamin D in health.

PMID- 19593103
TI  - Atraumatic fractures in heart failure.
AB  - Osteoporosis and heart failure are 2 highly prevalent conditions, particularly
      among the elderly, both of which account for significant morbidity and mortality.
      In this review, we describe the epidemiology of osteoporosis and osteoporotic
      related fractures in persons with heart failure. A review of the current
      literature regarding shared risk factors for heart failure and osteoporosis is
      presented, and potential common pathophysiologic mechanisms for these disorders
      are discussed.

PMID- 19593102
TI  - Vitamin D deficiency and risk for cardiovascular disease.
AB  - Vitamin D is an important prohormone for optimal intestinal calcium absorption
      for mineralization of bone. Because the vitamin D receptor is present in multiple
      tissues, there has been interest in evaluating other potential functions of
      vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional
      studies have reported that vitamin D deficiency is associated with increased risk
      of CVD, including hypertension, heart failure, and ischemic heart disease.
      Initial prospective studies have also demonstrated that vitamin D deficiency
      increases the risk of developing incident hypertension or sudden cardiac death in
      individuals with preexisting CVD. Very few prospective clinical studies have been
      conducted to examine the effect of vitamin D supplementation on cardiovascular
      outcomes. The mechanism for how vitamin D may improve CVD outcomes remains
      obscure; however, potential hypotheses include the downregulation of the renin
      angiotensin-aldosterone system, direct effects on the heart, and vasculature or
      improvement of glycemic control. This review will examine the epidemiologic and
      clinical evidence for vitamin D deficiency as a cardiovascular risk factor and
      explore potential mechanisms for the cardioprotective effect of vitamin D.

PMID- 19593104
TI  - Folic acid supplementation and cardiovascular disease: the state of the art.
AB  - High levels of homocysteine, a non-protein-forming, sulfur-containing amino acid,
      have been associated with elevated cardiovascular risk in observational studies.
      Support for the homocysteine hypothesis comes from 2 primary lines of
      epidemiologic evidence, observational studies, such as case control and cohort
      studies, and studies of genetic variation. On the basis of unequivocally
      supportive epidemiologic data, a series of large randomized controlled trials of
      homocysteine lowering through folic acid supplementation were launched. The
      recently reported results of the 3 large, randomized clinical trials (SEARCH,
      WENBIT, WAFACS) in combination with those previously reported (CHAOS-2, VISP,
      NORVIT, HOPE-2) effectively rule out the possibility of large effect on risk of
      coronary heart disease, stroke, and all-cause mortality. Although the potential
      for prevention of atherosclerotic cardiovascular disease in adults through folic
      acid supplementation has not yet been substantiated, folic acid supplementation
      prenatally may reduce congenital heart defects in offspring.

PMID- 19593105
TI  - The role of human papilloma virus in lung cancer: a review of the evidence.
AB  - Papillomaviruses are small nonenveloped DNA viruses that infect squamous
      epithelial cells. These viruses have been found in many organisms. Human
      papillomaviruses (HPVs) give rise to a large spectrum of epithelial lesions,
      mainly benign hyperplasia (eg, warts and papillomas) with low malignant
      potential. There is a subgroup of HPV, the "high-risk" HPV, which is associated
      with precancerous and cancerous lesions. A small fraction of people infected with
      high-risk HPV will develop cancers that usually arise many years after the
      initial infection (Psyrri and Dimaio, Nat Clin Pract Oncol. 2008;5:24-31).
      Nonsmall cell lung cancer is a heterogeneous disease. The most common histologic
      subtypes include squamous cell carcinoma, adenocarcinoma, and large cell
      carcinoma. Despite different histologies, nonsmall cell lung cancers are often
      classified together because of similarities in approach and management of the
      disease. In this article, we reviewed the current literature on lung cancer and
      HPV. On the basis of this data, we suggested a possible mechanism of
      carcinogenesis induced by HPV.

PMID- 19593106
TI  - Methotrexate-induced apoptosis is enhanced by altered expression of
      methylenetetrahydrofolate reductase.
AB  - Folates are essential for DNA synthesis and methylation reactions. The antifolate
      methotrexate (MTX) is a widely used chemotherapeutic drug which inhibits DNA
      synthesis and induces apoptosis. Changes in activity of a critical folate
      metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), might alter the
      chemosensitivity to MTX, as the MTHFR substrate is required for nucleotide
      synthesis and its product is used in homocysteine remethylation to methionine.
      Mild MTHFR deficiency is common in many populations due to a polymorphism at bp
      677. We previously showed that altered expression of MTHFR enhanced MTX-induced
      myelosuppression in mice. To determine the cause of the impaired hematopoietic
      profile in mice with decreased or increased MTHFR expression, we evaluated MTX
      induced apoptosis in the major hemolytic organ, spleen, using the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling
      (TUNEL) staining and caspase-3/7 activity assays, in MTHFR-deficient mice and in
      MTHFR-overexpressing mice after MTX administration. Decreased or increased
      expression of MTHFR in mice significantly increased TUNEL-positive cells and
      caspase-3/7 activities in MTX-treated spleen, compared with that of wild-type
      littermates. Plasma homocysteine levels correlated with apoptotic index in MTX
      treated MTHFR-deficient mice and dUTP/dTTP ratios correlated with apoptotic index
      in MTX-treated MTHFR-overexpressing mice. The increased apoptosis may therefore
      relate to hyperhomocysteinemia and deoxyribonucleotide pool imbalances,
      respectively. Our results suggest that MTHFR underexpression and overexpression
      enhances MTX-induced apoptosis and myelosuppression, and that genotyping for the
      MTHFR polymorphism may have therapeutic implications.

PMID- 19593107
TI  - Elective amputation of the toes in severe lymphedema of the lower leg: rationale
      and indications.
AB  - Entry lesions at the toes interdigital spaces, in the setting of chronic
      lymphedema, are strongly associated with repetitive infective episodes which
      cause significant morbidity. A prospective study was designed to evaluate the
      outcome in 2 groups of patients affected by end stage III lymphedema of the lower
      extremity, treated with the Charles procedure with or without simultaneous
      amputation of the toes. At a mean 3 years of follow-up, 20% of the patients
      receiving elective toes amputation experienced recurrence of the infection and
      none required more proximal amputations. Among the patients not desiring elective
      toes amputation; 83% suffered multiples attacks of cellulitis and in 88% the toes
      were eventually amputated. The difference in the number of infective episodes
      between the 2 groups was highly significant. No cases of recurrent lymphedema
      were registered. Elective toes amputation in combination with the Charles
      procedure reduces recurrent cellulitis and long-term morbidity in stage III
      lymphedema of the lower leg.

PMID- 19593108
TI  - A systematic review of abdominal wall function following abdominal flaps for
      postmastectomy breast reconstruction.
AB  - Perforator flap breast reconstruction potentially offers patients greater
      postoperative abdominal strength compared with traditional TRAM techniques. Our
      purpose was to perform a systemic review of the published literature regarding
      abdominal wall function following breast reconstruction and compare outcomes
      between pedicle TRAM, free TRAM, and perforator flap procedures. We used the
      MEDLINE, EMBASE, CINAHL, the Cochrane Network, and HAPI databases from January
      1966 through November 1, 2007 to identify potentially relevant studies. Inclusion
      criteria included studies that evaluated subjective or objective functional
      abdominal outcomes for postmastectomy patients receiving either pedicle TRAM,
      free TRAM, or deep inferior epigastric perforator (DIEP) flaps. All study designs
      were included in the review-prospective studies, cross-sectional studies, and
      retrospective case series. Our search yielded 20 studies on abdominal wall
      function after autogenous tissue breast reconstruction. Objective measures of
      abdominal wall function using isometric dynamometry revealed that pedicle TRAM
      patients experienced up to a 23% deficit, whereas free TRAM patients experienced
      up to an 18% deficit in trunk flexion. For trunk extension, pedicle TRAM patients
      experienced up to a 14% deficit, whereas free TRAM patients experienced minimal
      to no deficits. However, none of the comparative studies of pedicle and free TRAM
      procedures found significant differences in abdominal wall function between the 2
      groups. Studies that compared free TRAM to DIEP flaps found significantly higher
      flexion abilities in the DIEP groups, with one study reporting an advantage in
      measures of extension for DIEP flaps. Functional deficits assessed by
      physiotherapy measures revealed that patients with pedicle TRAM reconstructions
      experienced the greatest deficit in rectus and oblique muscle function (up to
      53%). Free TRAM groups experienced minimal deficit in rectus muscle function,
      whereas DIEP flaps returned to baseline for both rectus and oblique muscle
      function. Subjective measures of abdominal wall function were similar across
      unipedicle TRAM, free TRAM, and DIEP flap procedures. Patients with bilateral
      pedicle TRAM reconstruction suffered up to a 40% deficit in trunk flexion and up
      to a 9% deficit in trunk extension. Patients with bilateral pedicle or free TRAM
      reconstruction also experienced a significant decrease in the ability to perform
      sit-ups and a significant decrease in activities of daily living, recreational,
      and laborious activities. With the exception of those who had bipedicled TRAM or
      bilateral free TRAM procedures, most women reported return to their preoperative
      function without a decrease in their ability to perform activities of daily
      living. Although some studies report an objective advantage of DIEP flaps, this
      does not appear to translate to detriments in the performance of activities of
      daily living. However, the current data have limitations in study design and
      generalizability. A multicenter, longitudinal study is needed to assess objective
      and subjective outcomes in patients with pedicle TRAM, free TRAM, and perforator
      flaps using standardized and validated measures.

PMID- 19593109
TI  - Nerve decompression surgery as treatment for peripheral diabetic neuropathy:
      literature overview and awareness among medical professionals.
AB  - Peripheral diabetic neuropathy (PDN) is one of the major complications arising in
      patients with diabetes. Since PDN is traditionally considered an irreversible
      disorder, treatment has been aimed to prevent the development of complications.
      In a novel concept, however, it is postulated that decompression surgery of the
      affected nerve may reverse the natural course of PDN. In this review, we will
      discuss experimental and human studies that addressed the value of nerve
      decompression surgery in PDN. Furthermore, we report on the awareness of this
      novel treatment strategy among medical professionals that are primarily involved
      in diabetes care.

PMID- 19593110
TI  - Treatment of recalcitrant air leaks: the combined latissimus dorsi-serratus
      anterior flap.
AB  - Pleural space problems after lung resection and persistent air leaks are among
      the commonest challenges posed to thoracic surgeons. Surgical repair of air leaks
      are indicated when conventional tube thoracostomy has failed to solve the
      problem. We would like to propose the novel application of the combined
      latissimus dorsi-serratus anterior transposition flap for selected cases of air
      leaks that are recalcitrant to conventional treatment. We discuss its indications
      and the surgical technique. Five patients underwent the procedure between 2004
      and 2007. They were male patients aged between 32 and 70 years. Four patients had
      alveolar-pleural fistulas resulting in persistent air leaks while the fifth
      patient had, in addition, a space problem following lung volume reduction
      surgery. All patients had prolonged treatment with chest drains without success.
      With the patient in a lateral decubitus position, a lazy-S incision was used to
      expose the entire latissimus dorsi and the proximal slips of the serratus
      anterior muscles. They were raised as pedicled flaps and transferred in tandem.
      The latissimus dorsi was introduced into the pleural cavity via a thoracic window
      and used to reinforce the fistula repair. The serratus anterior muscle closed the
      rib window. In all cases, the lungs reexpanded and chest drains were removed
      within 5 days post surgery. There were no recurrent air leaks at 1-year follow-up
      with all patients. Conservative treatment in all our patients was unsuccessful.
      The dual flap technique has the advantage of allowing normal ventilation while
      providing a seal over the alveolar-pleural fistula. The muscle bulk of the
      latissimus dorsi fills the pleural dead space and the serratus anterior muscle
      seals the axilla preventing subcutaneous emphysema. There was minimal morbidity
      associated with the use of this dual muscle flap technique. This technique is an
      effective treatment option for recalcitrant air leaks.

PMID- 19593111
TI  - Benign peripheral nerve tumors: treatment algorithm and reconstructive options.
AB  - Peripheral nerve tumors are mostly benign; however, their excision can result in
      profound deficits. Nerve reconstruction strategies offer techniques to minimize
      morbidity. In this prospective study, 20 consecutive patients with benign
      peripheral nerve tumors were treated using a single-stage surgical paradigm
      between 2003 and 2007. Nerve fascicles were microdissected off of the tumor; any
      fascicle that gave origin to the tumor (was inseparable from tumor) was
      reconstructed using nerve conduits. Patients were followed from 6 to 24 months.
      All patients had neuropathic pain before tumor excision; only 1 patient had pain
      persist postoperatively. Seventeen patients had complete functional recovery
      after nerve reconstruction. No perioperative complications occurred. Benign
      peripheral nerve tumors require highly specialized surgical care. Tumor excision
      with immediate nerve reconstruction, for fascicles inseparable from the tumor,
      optimizes outcomes. Nerve reconstruction with available conduits or allografts
      should be attempted to restore anatomic integrity to any killed fascicles,
      thereby minimizing possible deficits.

PMID- 19593112
TI  - Anterolateral thigh perforator flap: varying perforator anatomy.
AB  - The anterolateral thigh (ALT) perforator flap is based on the septocutaneous or
      musculocutaneous perforators from the lateral circumflex femoral vessels. Each
      perforator artery should be accompanied by 2 veins. Anomalies of the perforator
      anatomy in the subfascia and intramuscular layer are rarely reported. This study
      analyzed 6 anatomic perforator variations from subfascial to intramuscular level
      out of 1043 ALT perforator flaps performed from 2005 to 2007 in China Medical
      University Hospital in Taichung, Taiwan and from 2004 to 2007 in E-Da Hospital in
      Kaohsiung, Taiwan. The perforator flaps included (1) 1 perforator artery and 4
      accompanying veins, (2) 1 perforator artery and 1 accompanying vein, (3) 1
      tortuous perforator artery and 1 accompanying vein, (4) 1 perforator artery with
      no accompanying vein, (5) 2 veins with no accompanying perforator artery, and (6)
      1 vein only. These variations in perforator anatomy were believed to be the
      causes of total or partial flap failure after excluding all the other
      possibilities such as vessel kinking or perforator injury during intramuscular
      dissection. Further, the nearby anteromedial thigh or tensor fasciae lata flaps
      were considered alternative flaps in cases of unusual perforator anatomy. The
      contralateral ALT flap was also necessary in some cases. However, anatomic
      variations in perforators from subfascial to intramuscular layer must be
      considered if the flap is to be used safely and reliably.

PMID- 19593113
TI  - The relationship between urokinase plasminogen activator/plasminogen activator
      inhibitor type-1 expression in myoma/myometrium and mechanism of uterine artery
      occlusion by laparoscopy for uterine myoma treatment.
AB  - The objective of the study was to investigate the pattern of expression of
      plasminogen activator/plasminogen activator inhibitor (PAI) system between myoma
      and myometrium and its correlation between outcome and laparoscopic uterine
      artery occlusion prior to myomectomy in the treatment of myoma. mRNA expression
      of PAI type-1 (PAI-1) and urokinase plasminogen activator (uPA) was detected with
      real-time PCR in the myoma and myometrium cells primary cultured in vitro, and
      uPA and PAI-I protein expression was detected with cellular immunity
      histochemistry. First, the expression of uPA mRNA was 0.123 +/- 0.189 in myoma,
      which was significantly lower than 0.331 +/- 0.306 in myometrium (P < 0.05);
      however, the expression of PAI-I mRNA was 0.091 +/- 0.036 in myoma, which was
      significantly higher than 0.016 +/- 0.020 in myometrium (P < 0.05). Second, the
      expression of uPA protein was 8.805 +/- 1.645 in myoma cells, which was lower
      than 22.173 +/- 4.381 in myometrium (P < 0.05); the expression of PAI-I protein
      was 44.765 +/- 1.090 in myoma cells, which was significantly higher than 35.928
      +/- 5.351 in myometrium (P < 0.05). The distinct expression pattern of uPA/PAI in
      myoma and myometrium might be correlated to the low recurrence rate after uterine
      artery occlusion prior to myomectomy in the treatment of myoma.

PMID- 19593114
TI  - Detection of the procoagulant activity of microparticle-associated
      phosphatidylserine using XACT.
AB  - One of the mechanisms by which platelet-derived microparticles elicit
      procoagulant activity is by an increased exposure of phosphatidylserine on their
      surface. We have previously demonstrated the utility of an activated factor X
      based assay for the detection of procoagulant phospholipid activity [Xa clotting
      time (XACT)]. The objective of this study was to further characterize the
      specificity of the XACT to detect microparticle-associated procoagulant
      phospholipid activity. XACT testing for procoagulant phospholipid was measured
      using an ST4 machine and microparticle counting was performed using flow
      cytometry for Annexin V binding. Plasma microparticle counts were significantly
      correlated to XACT times (P = 0.0001). The XACT assay was insensitive to tissue
      factor, whereas the addition of microparticles to a whole blood sample shortened
      XACT times. Procoagulant phospholipid activity could be detected in both citrate
      and EDTA anticoagulated samples; however, XACT times and microparticle counts
      were more stable in EDTA anticoagulated samples over a 60 min period. The
      procoagulant phospholipid activity of microparticles generated by collagen
      stimulation was significantly impaired in EDTA anticoagulated samples when
      compared with citrate. Microparticles were capable of higher degrees of thrombin
      generation than equivalent concentrations of phosphatidylserine (as assessed by
      XACT times), suggesting that other factors bound to the microparticle surface
      enhance the procoagulant response. In conclusion, the XACT assay is a specific
      method for the detection of procoagulant phospholipid activity arising from
      phosphatidylserine on the microparticle surface; however, other factors
      presumably bound to the surface of the microparticle may also contribute to
      enhanced thrombin generation detectable by prothrombinase assays.

PMID- 19593115
TI  - Hemophilia, cancer and cardiovascular disease.

PMID- 19593116
TI  - Acute myocardial ischemia in a patient with heterozygous alpha-2-plasmin
      inhibitor deficiency.
AB  - In this brief report we present a patient with heterozygous alpha2 plasmin
      inhibitor (alpha2PI) deficiency who developed atherosclerosis and myocardial
      ischemia in the presence of multiple classical risk factors. Management was
      complicated by fear of bleeding complications with the use of antiplatelet agents
      and serious comorbidity.The role of alpha2PI in atherosclerosis and pathological
      clot formation is still not clear. This case shows, however, that atherosclerosis
      and acute cardiovascular events can develop in patients with reduced alpha2PI
      levels.

PMID- 19593117
TI  - Clinical evaluation of a new functional test for detection of plasma procoagulant
      phospholipids.
AB  - The objective of this study was to validate a simple factor Xa-based clotting
      test developed to monitor procoagulant phospholipids (PPLs) and platelet-derived
      microparticles (PMPs). This assay is easily automated, giving it a major
      advantage over the more laborious and expensive flow cytometry, electron
      microscopy and ELISA techniques in general usage at present. The intra-assay and
      inter-assay variation coefficients were less than 5% at both low and high levels
      of PPLs. The test is not affected by other clotting factors is assured by the use
      of a phospholipid-free animal plasma, which provides excess factor V, fibrinogen
      and prothrombin. This test was evaluated in apparently healthy volunteers and in
      selected patient groups associated with increased levels of PMPs in the
      circulation (diabetes mellitus, sickle cell disease, thyroid cancer and patients
      with multiple trauma). The study showed that XaCT has a high discriminating power
      for PPLs and that the patient groups have significantly highly increased PPLs
      activities when compared with healthy volunteers. Although of a preliminary
      nature, the test has shown that it has the sensitivity for discriminating
      severity of disease, as it could detect patients in sickle cell crisis and
      differentiate between type 1 and 2 diabetes. In conclusion, the combination of
      reliability, reproducibility and easy performance makes the XaCT assay a simple
      test to screen for PPLs in plasma samples.

PMID- 19593118
TI  - Differences and effects of medium and large adult cuffs on blood pressure
      readings in individuals with muscular arms.
AB  - OBJECTIVE: This study analyzed systolic and diastolic blood pressure (SBP and
      DBP) reading differences in individuals with muscular arms, using medium and
      large adult cuffs. MATERIALS AND METHODS: Resting blood pressures (BPs) were
      measured in bodybuilders competing at the Mexican National Bodybuilding and
      Fitness Championship. The means of two bilateral simultaneous arm BP measurements
      were obtained using two different cuff sizes, 12 cm (medium adult) and 16 cm
      (large adult). RESULTS: A total of 193 bodybuilders completed the measurements.
      With an arm circumference greater than 33 cm, the SBP and DBP average taken with
      the medium adult cuff was higher than that obtained with the large adult cuff,
      8.2+/-10.6 and 1.6+/-7.4 mmHg, respectively; however, a significant difference
      was observed only with the SBP. With the medium adult cuff, 48 of 144 individuals
      showed SBP at least 140 mmHg, whereas with the large adult cuff there were only
      17 of 144 individuals. In those participants with an arm circumference less than
      33 cm, the BP was nonsignificantly lower with the large cuff, -4.24+/-9.2 and 
      2.24+/-5.4 mmHg for the SBP and DBP, respectively. CONCLUSION: Incorrect cuffing
      of a muscular arm leads to significant errors in the measurement of SBP and DBP,
      similar to that observed in miscuffing of nonmuscular arms.

PMID- 19593119
TI  - The role of acupuncture and transcutaneous-electrical nerve stimulation for
      postoperative pain control.
AB  - PURPOSE OF REVIEW: Both patients and care providers are concerned about the
      adverse events associated with pharmaceutical approaches used in postoperative
      pain management. Acupuncture and transcutaneous-electrical nerve stimulation
      (TENS) are complementary treatment techniques and are very popular in the
      management of a variety of painful conditions. Therefore, their use might help to
      reduce opioid requirements and decrease the incidence of medication-related
      adverse events. The aim of this review is to summarize the latest findings on the
      use of acupuncture and TENS in postoperative pain management. RECENT FINDINGS:
      The number of recent high-quality trials on acupuncture and TENS in postoperative
      pain is limited. Evidence of efficacy in acupuncture studies is contradictory
      although some high-quality studies clearly found positive effects. Differences in
      setting and methodology might explain the variability in the results. Findings of
      the few recent trials using TENS are consistently positive. SUMMARY: Evidence of
      efficacy in recent studies on acupuncture and TENS in management of postoperative
      pain is limited. However, some high-quality studies clearly show positive results
      for both methodologies. As these techniques cause no harm, their use as adjunct
      to conventional pharmaceutical approaches could be considered particularly for
      patients in whom conventional techniques fail and/or are accompanied by severe
      medication-related adverse events.

PMID- 19593120
TI  - Local anaesthetic adjuvants: neuraxial versus peripheral nerve block.
AB  - PURPOSE OF REVIEW: To present a review of the literature on the importance and
      the clinical characteristics relevant to adjuvants added to local anaesthetics in
      neuraxial and peripheral nerve blocks. RECENT FINDINGS: In neuraxial anaesthesia,
      both opioids and alpha-2 receptor agonists have beneficial effects.
      Intrathecally, fentanyl and sufentanil not only improve the postoperative
      analgesia but also make it possible to allow a decrease in the local anaesthetic
      dose. When clonidine or dexmedetomidine was added to intrathecal local
      anaesthetics, the regression of sensory, motor block increased dose-dependently
      and postoperative analgesia was prolonged. The potency of intrathecal clonidine:
      dexmedetomidine seems to be 10: 1. In peripheral nerve block, when opioid was
      combined with local anaesthetics, no increased improvement in analgesia was
      reported in comparison with systemic controls in most of the studies, except
      buprenorphine. Also clonidine is controversial as an analgesic adjuvant. Special
      factors, such as type of local anaesthetics, block of upper or lower limb, are
      important for its the beneficial effect. Other adjuvants, except neuraxial low
      dose neostigmine, are of minor importance. SUMMARY: Opioids and alpha-2 receptor
      agonists are important as neuraxial adjuvants to improve the quality of
      peroperative and postoperative analgesia in high-risk patients and in ambulatory
      procedures. In peripheral nerve blocks, however, some benefit is found only when
      clonidine is added to local anaesthetics under certain circumstances.

PMID- 19593121
TI  - Three-dimensional echocardiography for assessment of mitral valve regurgitation.
AB  - PURPOSE OF REVIEW: Estimation of severity has become a significant predictor of
      outcomes and a pivotal factor in the management of mitral regurgitation. The flow
      convergence formula has become one of the most important quantitative methods for
      valve regurgitation in echocardiography. Nevertheless, it has many assumptions
      leading to over or underestimations. With recent development of a much improved
      three-dimensional volumetric imaging, there have been efforts in trying to
      overcome these two-dimensional limitations using three-dimensional approaches.
      Hence, this review is mainly focused on three-dimensional color flow and
      techniques of quantifying the severity of mitral regurgitation using three
      dimensional echocardiography. RECENT FINDINGS: Investigators have found that
      imaging the proximal flow convergence region (PFCR) and measuring the vena
      contracta area are highly feasible. The shape of the PFCR may vary, being a
      hemisphere, prolate or oblate hemispheroid, or hemi-ellipsoid, based on these
      findings; three-dimensional formulas have a stronger correlation, less
      underestimation and better accuracy than the two-dimensional proximal isovelocity
      surface area method. Direct measurements of the effective regurgitant orifice are
      also feasible and serve as an alternative to hemodynamic formulas. SUMMARY: Three
      dimensional echocardiography has made major advances with the three-dimensional
      matrix transesophageal echo and will be a clinically viable tool as probe
      technology and software evolve.

PMID- 19593122
TI  - Imaging methodology and protocols for three-dimensional echocardiography.
AB  - PURPOSE OF REVIEW: Three-dimensional echocardiography (3DE) is an additional
      ultrasound modality that is poised to become an integral part of the routine
      echocardiogram. Incorporating 3DE into clinical daily practice continues to be a
      challenge for many laboratories. The following review will focus on workflow
      processes related to methodology and protocols in order to incorporate 3DE into
      clinical practice. RECENT FINDINGS: Several studies have shown the clinical
      utility and feasibility of both transthoracic and transesophageal 3DE. In
      addition, many centers performing 3DE studies utilize a focused 3DE protocol as
      opposed to a full 3DE protocol. A majority of the studies noted limitations with
      respect to artifacts inherent in gated imaging and preferred real-time 3DE or
      rather volume imaging. A recurrent message from several recent publications is
      that the ultimate success and widespread clinical application of 3DE will rely
      mainly on improved 3D image resolution and volume rates. SUMMARY: Continuous
      technology improvements have led to real-time full-volume 3D imaging that is no
      longer prone to the artifact issues encountered with gated 3D imaging. Additional
      improvements to 3DE image quality and time-saving automatic quantitative analysis
      tools will continue to define the emerging role for routine 3DE.

PMID- 19593123
TI  - Lipoprotein modification by secretory phospholipase A(2) enzymes contributes to
      the initiation and progression of atherosclerosis.
AB  - PURPOSE OF REVIEW: Secretory phospholipase A2s (sPLA2s) are considered to be
      important enzymes in the initiation and progression of atherosclerosis. In this
      review, we discuss the various mechanisms by which the direct action of the
      sPLA2s on LDL particles in the arterial intima may contribute to atherogenesis.
      RECENT FINDINGS: A wealth of evidence, both in vitro and in vivo, supports a role
      for the sPLA2s in atherogenesis. Very recently, systemic inhibition of sPLA2s was
      found to reduce measures of arterial inflammation. The mechanisms behind this
      inhibition, however, are largely unknown. Here, we discuss the consequences of
      sPLA2 action on LDL in the arterial intima and address the recent findings
      regarding the effects of the lipolytic products of sPLA2,
      lysophosphatidylcholine, and fatty acids on intimal cells. LDL modified by sPLA2
      can accumulate in the arterial intima both extracellularly and intracellularly.
      Importantly, the lipolytic products promote atherosclerosis by
      monocyte/macrophage recruitment, by enhancing the production of proretentive
      molecules by vascular smooth muscle cells, and by inducing cell death. SUMMARY:
      Recent findings on sPLA2s support the idea that the enzymes contribute to human
      atherogenesis not only as initiating agents but also in maintaining plaque
      inflammation.

PMID- 19593124
TI  - Relationship between LDL, HDL, blood pressure and atheroma progression in the
      coronaries.
AB  - PURPOSE OF REVIEW: To highlight clinical trials that have employed coronary
      artery imaging to evaluate the impact of medical therapies that target
      established cardiovascular risk factors. RECENT FINDINGS: High resolution imaging
      of the entire vessel wall permits assessment of changes in the full extent of
      coronary atherosclerosis. Intensive lowering of LDL cholesterol and systolic
      blood pressure are associated with the greatest benefit in terms of slowing
      disease progression. Therapeutic approaches that promote the biological activity
      of HDL have the potential to promote regression of atherosclerotic plaque.
      Targeting inflammatory cascades may also have a beneficial effect on the extent
      and composition of coronary plaque. SUMMARY: Intensive modification of
      established risk factors has a profound impact on the natural history of atheroma
      progression.

PMID- 19593126
TI  - Iatrogenic neuropathies.
AB  - PURPOSE OF REVIEW: This review discusses the literature on peripheral neuropathy
      caused by medication-induced toxicity or immunological mechanism with special
      attention to recent advancements. RECENT FINDINGS: The number of reports of
      immune-mediated neuropathies associated with antitumor necrosis factor alpha
      (anti-TNFalpha) therapy is increasing. But long-term follow-up suggests that the
      cessation of anti-TNFalpha therapy is not always necessary. The cases of acute
      inflammatory demyelinating polyneuropathy induced by polyethylene glycol
      interferon alpha-2a and of polyradiculoneuropathy induced by polyethylene glycol
      interferon alpha-2b were reported for the first time, and the latter was
      associated with antiganglioside antibodies. The mechanism of chemotherapy-induced
      peripheral neuropathy is still in the process of being elucidated with the use of
      animal models or axonal excitability techniques. In the phase III Assessment of
      Proteasome Inhibitor for Extending Remissions trial, it proved that dose
      modification using a specific guideline improved bortezomib-induced peripheral
      neuropathy management. SUMMARY: Peripheral neuropathy can be associated with anti
      TNFalpha therapy or interferon alpha therapy, and to the contrary, anti-TNFalpha
      therapy or interferon alpha therapy may have potential as a treatment option for
      a spectrum of immune-mediated neuropathy, similar to a double-edged sword. To
      take advantage of the effect of chemotherapy and to reduce neurotoxicity, a
      guideline of dose modification is useful.

PMID- 19593125
TI  - Recent advances in motor neuron disease.
AB  - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is the most common and
      most aggressive form of adult onset motor neuron degeneration. Despite intensive
      research, riluzole remains the only drug with proven efficacy. The cause and
      pathogenesis of the motor neuron degeneration in ALS appears to be a complex and
      multifactorial process. In this study, we review recent advances in our
      understanding of the molecular basis of sporadic and familial forms of ALS and
      improvements in the treatment of ALS patients. RECENT FINDINGS: The discovery of
      mutations in the DNA/RNA-binding proteins transactive response DNA-binding
      protein 43 (TDP-43) and fused in sarcoma in familial ALS and the cytosolic
      sequestration of TDP-43 occurring in sporadic ALS opens new avenues in ALS
      research and suggests that altered RNA processing may be involved in the disease
      pathogenesis. The survival of ALS patients continues to increase most likely due
      to noninvasive respiratory ventilation, early percutaneous endoscopic gastrostomy
      and multidisciplinary care in ALS clinics. SUMMARY: Recent insights in the
      pathology and genetics of ALS have improved our understanding of motor neuron
      degeneration and will hopefully lead to novel treatment strategies in ALS.
      Awaiting these, the beneficial effect of multidisciplinary care of ALS patients
      on survival and quality of life has become clear.

PMID- 19593127
TI  - Management of myasthenic conditions: nonimmune issues.
AB  - PURPOSE OF REVIEW: To review some management issues in myasthenic disorders that
      are not part of the immune interventions. These are mainly related to
      pharmacotherapy of these conditions and side effects of various medications, but
      also referred to acute management of respiration in myasthenic crises. RECENT
      FINDINGS: Antisense compound inhibiting acetylcholine esterase has positive
      therapeutic effects during short-term administration, but further studies are
      needed to confirm its chronic effects. Pyridostigmine seems not to have an
      additional effect to 3-4 diaminopyridine in Lambert Eaton myasthenic syndrome.
      Bilevel positive airway pressure and other external respiratory supportive
      systems may prevent in some myasthenic crises the need for intubation or at least
      shorten it. Statins can aggravate myasthenia gravis but the risk is not well
      quantified, and these compounds are not completely contraindicated in myasthenia.
      SUMMARY: Further research of the above findings is still necessary to make them a
      solid conclusion for the management of the myasthenias.

PMID- 19593128
TI  - Nocturnal dosing and chronic kidney disease progression: new insights.
AB  - PURPOSE OF REVIEW: Several studies have identified the presence of altered
      diurnal blood pressure patterns, specifically elevated nighttime blood pressure
      in patients with chronic kidney disease. The lack of nocturnal decline in blood
      pressure is associated with markers of hypertensive target organ damage and
      predictive of long-term clinical outcomes. The purpose of this review is to
      summarize the literature in this area and explore the potential for use of
      nighttime blood pressure for improving risk stratification and as a therapeutic
      target. RECENT FINDINGS: The mechanisms of persistent elevation of blood pressure
      at night in chronic kidney disease are likely to be multifactorial, including
      altered sodium handling and sympathetic activation among others. Elevated
      nocturnal blood pressures have been shown to be associated with increased adverse
      clinical outcomes. Recent studies demonstrate that it is feasible to lower
      nocturnal blood pressure by modifying the time of administration of
      antihypertensive medications. SUMMARY: Currently, clinical blood pressure
      measurements are assessed and targeted for drug therapy. This article shows the
      importance of measuring ambulatory blood pressures, specifically nocturnal blood
      pressures to improve risk stratification. More research needs to be done to
      identify interventions that lower nighttime blood pressure, and test their
      efficacy in improving clinical outcomes.

PMID- 19593129
TI  - Solute carrier family 2, member 9 and uric acid homeostasis.
AB  - PURPOSE OF REVIEW: The goal of this article is to review the possible
      physiological roles of the recently identified urate transporter, solute carrier
      family 2 (facilitated glucose transporter), member 9 (SLC2A9), in the renal
      handling of urate. RECENT FINDINGS: Glucose transporter 9 is a high affinity
      hexose transporter encoded by the SLC2A9 gene found on human chromosome 4. The
      two splice variants SLC2A9b and SLC2A9a are expressed in the apical and
      basolateral membranes, respectively, of the proximal convoluted tubule. Recent
      reports have found significant correlations between two different sets of single
      nucleotide polymorphisms in SLC2A9. In one case, they are associated with
      increases in plasma urate levels and/or the incidence of hypertension or gout.
      The second set of single nucleotide polymorphisms correlate with hypouricaemia in
      Japanese patients. Expression of SLC2A9a and b in Xenopus laevis oocytes shows
      that these proteins mediate rapid urate fluxes and can exchange glucose for
      urate. Indirect evidence also suggests that the transporter is electrogenic.
      SUMMARY: This review proposes that SLC2A9 contributes significantly in two ways
      to the fluxes of urate across the proximal convoluted tubule. Firstly, the apical
      expression of SLC2A9b secretes urate back into the urine in exchange for lumenal
      glucose. Secondly, the basolateral membrane SLC2A9a could be the primary route
      for urate movement out of the epithelium into the peritubular space.

PMID- 19593130
TI  - Drug interactions in transplant patients: what everyone should know.
AB  - PURPOSE OF REVIEW: Adverse events due to drug-drug interactions remain a
      challenge in the postsurgical care of transplant recipients. A combination of
      potent and selective immunosuppressive drugs, which have a narrow therapeutic
      index, with medications for the treatment of comorbidities such as dyslipidemia,
      infection, psychiatric conditions, and hypertension, can lead to life-threatening
      drug-drug interactions. RECENT FINDINGS: There are a number of important drug
      drug interactions which are important for physicians to consider. It is critical
      to understand the pharmacodynamics and pharmacokinetics of drug-drug
      interactions, their potential impact on patient care, and the management
      strategies. SUMMARY: Close therapeutic drug monitoring and evaluation of drug
      specific side effects continue to be an important key to minimize adverse events
      due to drug-drug interactions.

PMID- 19593131
TI  - Comparison between oxybutynin, functional electrical stimulation and pelvic floor
      training for treatment of detrusor overactivity in women: a review.
AB  - PURPOSE OF REVIEW: Overactive bladder syndrome is a chronic condition
      characterized by urgency with or without urge incontinence, usually with
      frequency and nocturia. The usual urodynamic diagnosis is the presence of
      detrusor overactivity. Overactive bladder is a common condition that has a
      negative impact on the quality of life of the affected individuals. In this
      review we provide a summary of relevant recent publications concerning the
      effectiveness of oxybutynin, functional electrical stimulation and pelvic floor
      training alone or in combination for the management of this syndrome. RECENT
      FINDINGS: Oxybutynin, electrical stimulation and pelvic floor training are well
      tolerated and effective therapeutic options for overactive bladder. However, most
      patients do not achieve complete symptom relief with each therapy alone. Evidence
      for the efficacy of combination therapy over either treatment alone is scarce.
      SUMMARY: Future well designed randomized clinical trials are needed to determine
      whether combined drug and conservative treatments can improve clinical outcomes
      for patients with overactive bladder. Standardization of both the diagnostic
      criteria and exercise training programs might facilitate comparisons of the
      results obtained by different studies.

PMID- 19593132
TI  - Biomechanical properties of graft materials employed for pelvic floor
      reconstructive surgeries.
AB  - PURPOSE OF REVIEW: Numerous biomaterials are currently used to augment pelvic
      organ prolapse reconstructive surgeries. Understanding the biomechanical
      properties of the raw and implanted graft materials may lead to improvements in
      biomaterial design and development. This summary aims to review recent
      assessments and advances in the understanding of vaginal tissues and synthetic
      graft materials profiles. RECENT FINDINGS: Numerous meshes have been assessed and
      compared for various biomechanical properties. There is now an emphasis on more
      relevant mechanical tests rather than only comparing loads at failure.
      Development of tests at physiological loads is important in achieving relevance
      of biomechanical data. Comparisons of partly absorbable with nonabsorbable meshes
      both preimplantation and postimplantation, have shown no difference in
      biomechanical properties, thus promoting the use of less permanent components in
      meshes. Potential factors contributing to mesh exposure are presented. SUMMARY:
      Biomechanical testing of synthetic graft materials is moving towards achieving
      data relevant to physiological loads and clinical conditions. Modeling research
      is required to understand these physiological loads, and create relevant
      measurements which can then be used when biomechanically assessing both raw and
      implanted grafts.

PMID- 19593133
TI  - Effectiveness of midurethral slings in intrinsic sphincteric-related stress
      urinary incontinence.
AB  - PURPOSE OF REVIEW: Previous literature has shown that urodynamic evidence of
      intrinsic sphincter deficiency (ISD) decreases the surgical success of
      traditional antistress incontinence surgeries. The aim of this review is to
      assess recent evidence on the effectiveness of the increasingly popular
      midurethral slings (MUS) in women with ISD and stress urinary incontinence.
      RECENT FINDINGS: Using the ISD definition of maximum urethral closure pressure of
      20 cm H2O or less and/or abdominal/valsalva leak point pressure of 60 cm H2O or
      less, current literature would suggest that the effectiveness of retropubic MUS
      is reduced but remained acceptable in women with stress urinary incontinence and
      ISD. There are conflicting data on whether coexisting poor urethral mobility
      could further compromise surgical success. Of note, there is now emerging
      evidence to suggest that transobturator tapes are associated with much higher
      failure rates in this setting and retropubic MUS should be used instead.
      Currently, there is too little data on the new single-incision mini-slings for
      any recommendation of use in women with stress incontinence with good or poor
      intrinsic urethral function. SUMMARY: MUS is an effective treatment for stress
      urinary incontinence. However, when urodynamic evidence of ISD is present, the
      retropubic approach may be preferable to the transobturator approach.

PMID- 19593134
TI  - The effectiveness and complications of graft materials used in vaginal prolapse
      surgery.
AB  - PURPOSE OF REVIEW: In the last decade, there has been an increase in the use of
      graft materials in vaginal prolapse surgery. Most of the evidence available is
      based on case studies produced by the manufacturers, with few randomized
      controlled trials. In October 2008, the United States Food and Drug
      Administration issued a safety warning on the use of grafts in vaginal surgery.
      It has been suggested that there is a greater need to review the evidence on the
      effectiveness and complication of grafts. RECENT FINDINGS: This article explores
      the recent literature on the use of grafts in vaginal prolapse surgery. The use
      of grafts versus standard techniques for vaginal wall repair is examined, looking
      at subjective and objective cure as well as complications. SUMMARY: Despite the
      wide use of grafts in vaginal prolapse surgery, there is still a need for level 1
      evidence to support their use, with long-term follow-up of 3 or 5 years. There
      is, however, good evidence to support the use of grafts in suburethral slings and
      abdominal sacrocolpopexy.

PMID- 19593135
TI  - Progress in tailoring adjuvant endocrine therapy for postmenopausal women with
      early breast cancer.
AB  - PURPOSE OF REVIEW: Clinical trials have shown that a variety of aromatase
      inhibitor strategies modestly reduce the risk of breast cancer recurrence over 5
      years of tamoxifen for postmenopausal women with endocrine-sensitive disease.
      This review will discuss the use of predictive biomarkers to tailor
      postmenopausal endocrine therapy. RECENT FINDINGS: In spite of early promise,
      recent studies suggest that quantitative evaluation of estrogen receptor,
      progesterone receptor, and human epidermal growth factor receptor-2 expression do
      not identify a subgroup of patients with differential benefit from an aromatase
      inhibitor over tamoxifen therapy. Estrogen receptor-positive tumors with
      increased proliferation, evaluated by Ki-67, may be selectively responsive to
      aromatase inhibitor therapy. Growing evidence suggests that inherited
      polymorphisms in tamoxifen-metabolizing enzymes identify a subgroup of patients
      with poor outcome under tamoxifen therapy that might best be treated with an
      aromatase inhibitor. The emergence of early treatment-related side effects on
      either aromatase inhibitor or tamoxifen, such as hot flashes and anthralgias, has
      been linked to a decreased risk of recurrence, although additional validation is
      needed. SUMMARY: There are no robust clinically available tools that can be used
      to reliably identify patients that are likely to be selectively responsive to an
      aromatase inhibitor over tamoxifen alone. The decision to use an aromatase
      inhibitor in clinical practice should be primarily guided by consideration of
      recurrence risk and contraindications to tamoxifen.

PMID- 19593136
TI  - The role of sentinel node biopsy in gynecological cancer: a review.
AB  - PURPOSE OF REVIEW: In early-stage vulvar, cervical and endometrial cancer, lymph
      node status is the most important prognostic factor. Surgical treatment is aimed
      at removing the primary tumor and adequately staging the regional lymph nodes. As
      morbidity of regional lymphadenectomy is high, sentinel node biopsy is a
      technique with potential for adequate staging with less treatment-related
      morbidity. This manuscript reviews its current role in vulvar, cervical and
      endometrial cancer. RECENT FINDINGS: In early-stage vulvar cancer, level 3
      evidence indicates that it appears to be safe to omit inguinofemoral
      lymphadenectomy in case of a negative sentinel node. However, false-negative
      results with fatal consequences do occur and are often attributable to procedural
      failures. For early-stage cervical cancer, level 3 evidence points to an
      acceptable false-negative rate of a negative sentinel node; clinical utility and
      safety remain to be established. The optimal technique of the sentinel node
      biopsy in endometrial cancer is currently unclear. SUMMARY: In early-stage vulvar
      cancer, data suggest that sentinel node biopsy could be offered as a treatment
      option instead of routine inguinofemoral lymphadenectomy. However, more (long
      term follow-up) data are needed to further appreciate real clinical benefits. It
      is emphasized that the procedure should be performed by a skilled
      multidisciplinary team, centralized in oncology centers and preferably within the
      protection of clinical trials. For cervical cancer, data are promising, but
      routine application cannot be recommended due to lack of data on clinical utility
      and safety. For endometrial cancer, studies on the sentinel node biopsy are still
      in feasibility stage.

PMID- 19593137
TI  - Primary central nervous system lymphoma: recent progress, many remaining
      questions.
AB  - PURPOSE OF REVIEW: To review what progress has been made in the treatment of
      primary central nervous system lymphoma since the time when it was first
      recognized that high-dose methotrexate based chemotherapy improved outcome over
      radiation therapy alone. RECENT FINDINGS: Recent work has explored the use of
      high-dose methotrexate alone; the optimum dose of methotrexate; the need for
      intrathecal therapy; combinations of other drugs with high-dose methotrexate,
      most notably alkylators, high-dose cytarabine, and rituximab; and the use of
      myeloablative chemotherapy and autologous stem-cell rescue. Recent progress has
      also been made in the identification of clinical prognostic factors, and in
      identifying underlying biologic properties that may account for this tumor's
      distinctive clinical behavior. SUMMARY: Further improvement in progression-free
      survival and in the proportion of patients achieving long-term disease-free
      survival does seem to be achievable, based on the results of nonrandomized data.
      Reduction in the risk of severe neurotoxicity by withholding or deferring
      radiation therapy also appears feasible. Existing treatment options can be
      individualized to the patient's circumstances. However, the optimal management of
      primary central nervous system lymphoma remains to be defined, and participation
      in a suitable clinical trial is highly appropriate.

PMID- 19593138
TI  - Localized large cell lymphoma: is there any need for radiation therapy?
AB  - PURPOSE OF REVIEW: Diffuse large B-cell lymphoma is the most common lymphoma
      diagnosed in the United States and presents as localized disease in about 25% of
      the patients. The standard of care was established by Southwest Oncology Group
      trial 8736, which showed the superiority of a short course of chemotherapy
      followed by radiation over a longer course of chemotherapy alone. This review
      discusses the studies that followed with the intent to establish whether the
      standard of care has changed. RECENT FINDINGS: Subsequent studies examined the
      role of radiation therapy, the number of cycles and intensity of chemotherapy,
      and addition of rituximab. Interpretation of results has been confounded by
      patient selection, especially by including patients with bulky stage II disease.
      Quality of radiation therapy may have diminished its efficacy in some of the
      studies. Concurrent administration of rituximab provided a more modest
      improvement as compared with advanced disease setting. Attempts are now made to
      use PET scans to eliminate the need for radiation therapy in some patients.
      SUMMARY: Radiation therapy remains useful when administered expediently and as
      initially described, but PET scans successfully define a subset of patients who
      do not benefit from radiation. Using a longer or more intensive course of
      rituximab-containing chemotherapy without radiation has never been compared to
      combined modality treatment and remains investigational.

PMID- 19593139
TI  - Low-molecular-weight heparin for thromboprophylaxis.
AB  - PURPOSE OF REVIEW: Venous thromboembolism represents a potentially threatening
      complication in surgical and medical patients. Thromboprophylaxis showed a
      significant reduction of venous thromboembolic events, and low-molecular-weight
      heparins have been considered the standardized prophylactic regimen for a long
      time. The purpose of this review is to provide updated evidence on the use of low
      molecular-weight heparins for prevention of venous thromboembolism after the
      publication of the latest American College of Chest Physicians Evidence-Based
      Clinical Practice Guidelines on antithrombotic and thrombolytic therapy. RECENT
      FINDINGS: Low-molecular-weight heparins, used as comparator or investigational
      drug, have been investigated in several studies not included in the analysis of
      the latest American College of Chest Physicians Guidelines on Antithrombotic and
      Thrombolytic Therapy. Data gathered from studies published from December 2007 up
      to May 2009 dealing with surgical and medical patients have been collected and
      discussed. SUMMARY: Low-molecular-weight heparins are expanding their
      application, but progressively they will be replaced by other new antithrombotics
      for the prophylaxis of venous thromboembolism. Surgical patients undergo a more
      concerted approach to thromboprophylaxis than medical patients. Future research
      should aim at improving prophylaxis in the latter setting in order to
      significantly reduce the rate of venous thromboembolic events.

PMID- 19593140
TI  - Proteomic analysis in interstitial lung diseases: a review.
AB  - PURPOSE OF REVIEW: This article aims to review the most recent proteomic findings
      in tissue and biological fluids and application of new technologies for the study
      of interstitial lung diseases. RECENT FINDINGS: New insights into lung cell
      biology as well as novel pathogenetic pathways of different interstitial lung
      diseases, potential targets of treatment and specific biomarkers discovered by
      proteomics have been reported. Proteomics has been applied to different kinds of
      biological fluids and the most promising material for proteomic analysis of
      interstitial lung disease is currently bronchoalveolar lavage fluid. SUMMARY: The
      results from proteomic studies on this field could be useful in clinical practice
      for diagnosis, disease progression and severity of interstitial lung diseases.

PMID- 19593141
TI  - Targeting interleukin-6 in pediatric rheumatic diseases.
AB  - PURPOSE OF REVIEW: To describe the most recent data regarding the role of
      interleukin-6 (IL-6) in immune and inflammatory responses, the mode of action and
      safety information on tocilizumab, the only available IL-6 inhibitor, and discuss
      recent results on the therapeutic inhibition of IL-6 in pediatric rheumatic
      diseases. RECENT FINDINGS: New data on the effects of IL-6 on T and B cells have
      been published. Clinical trials with tocilizumab in adults, particularly with
      rheumatoid arthritis, provide new data on mechanism of action and a reasonably
      wide safety database. A withdrawal design trial showed marked efficacy in
      systemic juvenile idiopathic arthritis (s-JIA). Open label studies or anecdotal
      reports suggest possible efficacy also in other JIA subtypes, as well as other
      rheumatic diseases. SUMMARY: Targeting IL-6 activities is an effective approach
      in the treatment of chronic inflammatory diseases. The long-term benefit and
      safety of tocilizumab have to be defined in long-term extension studies. The
      risk/benefit ratio appears to be particularly favorable in s-JIA. With the
      increasing number of biologics becoming available, future efforts should be
      directed to the definition of biomarkers that will identify responders to each
      novel biologic, allowing a personalized approach.

PMID- 19593142
TI  - Drug-induced autoimmunity.
AB  - PURPOSE OF REVIEW: This review aims to draw attention to the increased spectrum
      of the features of drug-induced autoimmunity (DIA), including both clinical and
      autoantibody profiles in addition to the potential chronicity of the syndrome.
      RECENT FINDINGS: In recent years, not only has the number of medications causing
      DIA increased but the spectrum of the features has broadened as well. With the
      use of newer medications, especially biologics, mostly directed towards immune
      system manipulation, the range of signs and symptoms of DIA as well as the
      patterns of autoantibody profiles have widened. Rashes and visceral involvement
      have started to be reported more often, especially with tumor necrosis factor
      antagonists. In addition, autoantibodies such as antidouble-stranded DNA, which
      are usually seen with idiopathic systemic lupus erythematosus, are appearing in
      place of the antihistone antibodies, typically found in drug-induced lupus.
      Finally, some medications have been implicated in causing the very same entity,
      which they may be used to treat. It is clear that progress in the field of
      pharmacogenetics and pharmacogenomics will help further our understanding of
      these and other adverse effects of medications. SUMMARY: Even though DIA has been
      known for many years, the underlying mechanisms remain unclear. However, with
      recently described new and unexpected features, novel hypotheses have been
      proposed, thus opening doors to further research in understanding these
      mechanisms.

PMID- 19593143
TI  - Genetics of systemic lupus erythematosus and Sjogren's syndrome.
AB  - PURPOSE OF REVIEW: To determine the advances made in the genetics of systemic
      lupus erythematosus (SLE) or Sjogren's syndrome as the era of genome-wide
      association and high-throughput single nucleotide typing begins. RECENT FINDINGS:
      Several genome-wide association studies have been performed in SLE but there are
      no such studies published or in progress for Sjogren's syndrome. Genetics and the
      functional significance of risk alleles in the interferon pathway are being
      worked out in detail. This is especially true for STAT4 and IRF5. Gene copy
      number variation, a major source of genetic variability, is important for several
      genes that impart risk for SLE. An X chromosome copy number dose effect has
      recently been identified. Genetic evaluation of Sjogren's syndrome is limited to
      small studies that have concentrated on genes already shown to be risk factors in
      SLE. SUMMARY: Knowledge of the genetics of SLE is advancing rapidly, whereas that
      of Sjogren's syndrome lags behind considerably.

PMID- 19593144
TI  - Antiphospholipid syndrome and systemic lupus erythematosus: are they separate
      entities or just clinical presentations on the same scale?
AB  - PURPOSE OF REVIEW: Although originally described in the context of systemic lupus
      erythematosus, antiphospholipid syndrome was then recognized as a primary
      antiphospholipid syndrome without any underlying autoimmune disease in almost
      half of the cases. However, cases of primary antiphospholipid syndrome were
      reported to evolve into systemic lupus erythematosus over time suggesting that
      these apparently different diseases are somehow related. RECENT FINDINGS:
      Peculiar biological systemic lupus erythematosus markers such as an autoantibody
      response against chromatin antigens and complement activation have been also
      described in patients with primary antiphospholipid syndrome. Distinct
      polymorphisms of common genetic factors have been associated with systemic lupus
      erythematosus and primary antiphospholipid syndrome supporting the notion that
      these entities are indeed variants within a continuum of the same disease.
      SUMMARY: A multiorgan involvement that cannot be explained by the thrombophilic
      state per se and similar to the well known clinical manifestations in lupus is
      reported in patients with primary antiphospholipid syndrome. Further studies,
      mainly genetic, will better underline the proximity between primary
      antiphospholipid syndrome and systemic lupus erythematosus.

PMID- 19593145
TI  - The Simplified Predictive Intubation Difficulty Score: a new weighted score for
      difficult airway assessment.
AB  - BACKGROUND AND OBJECTIVE: Using the Intubation Difficulty Scale (IDS) more than 5
      as a standardized definition of difficult intubation, we propose a new score to
      predict difficult intubation: the Simplified Predictive Intubation Difficulty
      Score (SPIDS). METHODS: We prospectively studied 1024 patients scheduled for
      elective surgery under general anaesthesia. Using bivariate and multivariable
      analysis, we established risk factors of difficult intubation. Then, we assigned
      point values to each of the adjusted risk factors, their sum composing the SPIDS.
      We assessed its predictive accuracy using sensitivity, specificity, positive
      (PPV) and negative predictive values (NPV), and the area under the receiver
      operating characteristic (ROC) curve (AUC), and compared it with the
      corresponding nonweighted score. The optimal predictive level of the SPIDS was
      determined using ROC curve analysis. RESULTS: We found five adjusted risk factors
      for IDS more than 5: pathological conditions associated with difficult intubation
      (malformation of the face, acromegaly, cervical rheumatism, tumours of the
      airway, and diabetes mellitus), mouth opening less than 3.5 cm, a ratio of
      patient's height to thyromental distance 25 at least, head and neck movement less
      than 80 degrees , and Mallampati 2 at least. Sensitivity, specificity, PPV and
      NPV of the SPIDS were 65, 76, 14 and 97%, respectively. AUC of the SPIDS and the
      nonweighted score (obtained previously using a stepwise logistic regression) were
      respectively 0.78 [95% confidence interval (CI) 0.72-0.84] and 0.69 (95% CI 0.64
      0.73). The threshold for an optimal predictive level of the SPIDS was above 10 of
      55. CONCLUSION: The SPIDS seems easy to perform, and by weighting risk factors of
      difficult intubation, it could help anaesthesiologists to plan a difficult airway
      management strategy. A value of SPIDS strictly above 10 could encourage the
      anaesthesiologists to plan for the beginning of the anaesthetic induction with
      'alternative' airway devices ready in the operating theatre.

PMID- 19593146
TI  - Volatile induction/maintenance of anaesthesia with sevoflurane increases jugular
      venous oxygen saturation and lumbar cerebrospinal fluid pressure in patients
      undergoing craniotomy.
AB  - BACKGROUND AND OBJECTIVE: Sevoflurane is a widely used volatile agent in
      neuroanaesthesia, and its nonirritant properties on the respiratory tract make
      sevoflurane suitable for volatile induction/maintenance of anaesthesia (VIMA). In
      the current trial, we investigate the effects of sevoflurane VIMA on lumbar
      cerebral fluid pressure (LCSFP) and jugular venous oxygen partial pressure in
      patients undergoing craniotomy for supratentorial intracranial surgery under
      bispectral index monitoring, determine jugular bulb venous oxygen saturation
      (SjvO2) and calculate cerebral perfusion pressure (CPP), arteriojugular venous
      oxygen content difference and cerebral oxygen extraction rate (COER) at different
      time points during the operation. Moreover, we compare these with total
      intravenous anaesthesia (TIVA) in patients receiving remifentanil and propofol
      continuous infusion. METHODS: Twenty-six adult patients undergoing elective
      craniotomy were randomly allocated to either remifentanil-propofol (group TIVA)
      or sevoflurane (group VIMA). Mean arterial blood pressure, heart rate, LCSFP,
      CPP, SjvO2, arteriojugular venous oxygen content difference and COER were
      compared in the two groups at different time points under bispectral monitoring.
      Heart rate, mean arterial blood pressure, saturation of peripheral oxygen, BIS
      value and LCSFP were recorded at the time points including intubation (Tintub), 5
      min (T5'int) and 15 min (T15'int) after intubation, the beginning of surgery
      (Tsurg), 5 min (T5m), 0.5 h (T0.5h), 1 h (T1h), 1.5 h (T1.5h), 2 h (T2h) and 2.5
      h (T2.5h) after incision, the end of surgery (Tend), extubation (Textub) and 30
      min (T30'end) after surgery. Arterial blood gas and jugular venous bulb blood gas
      analysis were performed at the time points of T0, T5'int, T5m, T1h, T2h, Tend, 15
      min after operation (T15'end) and T30'end. RESULTS: LCSFP was increased above
      baseline levels in group VIMA and decreased in group TIVA from Tintub to T5m, and
      decreased to similar levels from T0.5h to T30'end in both groups. Mean arterial
      blood pressure was decreased to similar levels from T0.5h to Tend and returned to
      baseline levels at T30'end in both groups, and was significantly higher in group
      VIMA than in group TIVA at T5'int, T15'int, Tsurg and T5m. CPP was decreased to
      similar levels between the groups from T0.5h to Tend and returned to baseline
      levels at T30'end in both groups, and was significantly higher at Tintub, T5'int
      and T15'int in group VIMA than in group TIVA. Jugular venous oxygen partial
      pressure and SjvO2 were increased above baseline level from T5'int to T30'end in
      group VIMA, and decreased from T5'int to Tend, and returned to baseline level at
      T30'end in group TIVA. Arteriojugular venous oxygen content difference and COER
      were decreased from T5'int to T30'end in group VIMA, and increased above the
      baseline level from T5'int to Tend, and returned to the baseline level at T30'end
      in group TIVA. CONCLUSION: Sevoflurane VIMA increases SjvO2, lumbar CSF pressure
      and CPP, and decreases COER, which suggested that VIMA could be a better choice
      for patients with the risk of cerebral hypoperfusion or insufficient oxygen
      delivery. Propofol-based TIVA is associated with decreased SjvO2, LCSFP and CPP,
      and increased COER, and it might be suitable for patients with increased
      intracranial pressure.

PMID- 19593147
TI  - Premature preoperative discontinuation of antiplatelet drug therapy in
      cardiovascular risk patients: a preliminary study on the role of P2Y12 receptor
      monitoring.
AB  - BACKGROUND AND OBJECTIVE: In high-bleeding risk procedures, discontinuation of
      antiplatelet drug therapy with clopidogrel may be requested by surgeons, usually
      7-10 days before the surgical procedure. New platelet function tests, such as the
      vasodilator-stimulated phosphoprotein phosphorylation assay, may help to assess
      the perioperative status of the clopidogrel-specific P2Y12 receptor. METHODS:
      Using vasodilator-stimulated phosphoprotein phosphorylation assay, the platelet
      reactivity index (PRI) was measured in 80 individuals, including 20 healthy
      volunteers, 20 cardiologic patients under full antiplatelet drug therapy with
      clopidogrel and aspirin, 20 surgical patients without any antiplatelet drugs and
      20 patients under clopidogrel, discontinued 7 days before the surgical procedure.
      RESULTS: The mean PRI (95% confidence interval) in healthy volunteers was 86 (82
      89%) and that in the surgical control group was 77% (72-81%). In cardiologic
      patients under full antiplatelet therapy, mean PRI was 51% (42-60%). In the
      clopidogrel discontinuation group, PRI increased from 51% (40-62%) on day 0 to
      65% (57-74%) on day 3 and to 76% (69-84%) on day 5. On the morning of surgery,
      mean PRI was 85% (80-91%). The PRI values on the 5th day were equivalent to those
      of the surgical control group (mean difference -0.4%, 95% confidence interval 
      8.6% to 7.8%, P = 0.9). Fifty-five percent of the patients in the discontinuation
      group had a PRI of more than 50% on day 0. CONCLUSION: The study using
      vasodilator-stimulated phosphoprotein phosphorylation assay, one of the new
      platelet function assays for the assessment of inhibition of platelet P2Y12
      receptor, demonstrates that the PRI on day 5 after discontinuation of clopidogrel
      is equivalent to a surgical control group and it questions the rigid practice of
      delaying surgery for 7-10 days, particularly in patients without a clopidogrel
      effect.

PMID- 19593148
TI  - A comparison of the Laryngopharyngeal Examination blade and the English Macintosh
      laryngoscope blade using an intubating manikin: a prospective randomized
      crossover study.
AB  - BACKGROUND AND OBJECTIVE: To compare the new design laryngoscope blade,
      Laryngopharyngeal Examination blade, with the English Macintosh blade for
      examination of the laryngopharynx and placement of a nasogastric tube in the
      presence of a tracheal tube, time taken to insert the nasogastric tube and for
      tracheal intubation in an adult intubation manikin. METHODS: A prospective
      randomized and crossover trial with 81 anaesthetists of different expertise
      taking part in the study. Ease of laryngoscopy and tracheal intubation,
      examination of hypopharynx and time taken to insert the nasogastric tube were
      measured using the new design laryngoscope blade compared with the Macintosh
      blade in a manikin. RESULTS: Using the new design blade, examination of the
      hypopharynx was found easier by 75% of participants and insertion of nasogastric
      tube after tracheal intubation was found easier by 77% of participants. Time
      taken to insert the nasogastric tube was shorter with the new design blade. Ease
      of laryngoscopy and tracheal intubation using the new design laryngoscope blade
      was found to be comparable or superior to the Macintosh blade by 68% of the
      participants. CONCLUSION: We conclude that, in a manikin, the new design blade
      can make nasogastric tube insertion easier when compared with the Macintosh blade
      and it can be used to facilitate laryngoscopy and tracheal intubation. Further
      studies are needed to evaluate its use in patients.

PMID- 19593149
TI  - Serum calcium and tumour aggressiveness in breast cancer: a prospective study of
      7847 women.
AB  - Experimental, epidemiological and clinical studies suggest that calcium and/or
      its regulating hormones affect breast cancer risk. There has been no prospective
      cohort study investigating serum calcium levels and breast cancer aggressiveness,
      as determined by tumour histology and stage. Dichotomized prediagnostic serum
      calcium levels were investigated in relation to breast cancer aggressiveness as
      determined by grade (mitotic frequency, tubule formation, nuclear atypia) and
      stage (tumour size and axillary lymph node status). Cox's proportional hazards
      analysis and heterogeneity analysis were used to investigate the associations
      between low/high calcium and grade/stage in a prospective cohort study of 7847
      women, out of whom 462 women were diagnosed with incident breast cancer during a
      mean follow-up of 17.2 years. All analyses were stratified for body mass index
      and menopausal status. Prediagnostic serum calcium levels in premenopausal women
      were positively associated with increased tumour aggressiveness as determined by
      a higher risk of nodal metastasis; relative risk (RR) for calcium above median as
      compared with calcium below median was 1.88 with a 95% confidence interval (CI)
      of 1.04-3.38. In overweight women, prediagnostic serum calcium levels were also
      associated with tumour aggressiveness, as determined by both a higher risk of
      nodal metastasis [RR (95% CI) 1.69 (0.95-3.02)] and severe nuclear atypia [RR
      (95% CI) 2.06 (1.10-3.86)]. Results also indicate that, in overweight women,
      calcium is positively associated with worse grade as determined by tubule
      formation and mitotic frequency. In conclusion, prediagnostic serum calcium
      levels are positively associated with increased tumour aggressiveness in
      premenopausal and/or overweight women.

PMID- 19593151
TI  - Topical anaesthesia in children: reducing the need for specialty referral.
AB  - OBJECTIVE: The management of wounds in children is stressful, not only for the
      child, but also for parents and staff. In our Emergency Department (ED), we
      currently do not have a paediatric sedation policy, and thus children requiring
      suturing, not amenable to distraction and infiltrative anaesthesia, are referred
      to specialty teams for general anaesthesia. We proposed that the introduction of
      a topical anaesthetic gel (lidocaine, adrenaline, tetracaine - LAT) might help to
      reduce the number of referrals, by allowing the ED staff to perform the
      procedures, in combination with nonpharmacological approaches. METHODS: We
      carried out a retrospective review of ED records of all children aged 14 years or
      less attending with wounds, over an 8-month period, from 01 May 2007 to 31
      January 2008. RESULTS: Two hundred and one (50.6%) patients presented before the
      introduction of LAT gel, whereas 196 (49.3%) patients presented afterwards. A
      total of 39 (19.4%) patients were referred for specialty review pre-LAT, whereas
      only 19 (9.7%) patients were referred in the LAT group. Of these, 31 (15.4%) pre
      LAT and 15 (7.7%) LAT group required general anaesthesia. There is a significant
      difference between these two groups, using Fischer's exact test, P=0.018.
      CONCLUSION: We have found that the introduction of topical anaesthetic gel in ED
      has significantly reduced the number of children with wounds referred to
      specialty teams for general anaesthesia. This has important implications for
      patient safety and hospital resources.

PMID- 19593150
TI  - Food and vessels: the importance of a healthy diet to prevent cardiovascular
      disease.
AB  - AIM: We attempted to quantify the burden of cardiovascular disease that can be
      prevented by broader adherence to recommendations on dietary intake of key
      nutrients. METHODS: A computer model capturing the epidemiology of chronic
      disease and risk factors in the Dutch population was used to simulate differences
      in the occurrence of cardiovascular disease under various scenarios defined by
      levels of intake of saturated and trans fatty acids, fruit, vegetables and fish.
      The following scenarios were compared with the current situation: (i) the whole
      population adhering to recommendations (optimum scenario); (ii) a moderate
      improvement and (iii) increased intake of fruit as has been achieved in an actual
      intervention ('fruit at work'). Other outcome measures assessed were (differences
      in) life expectancy and healthy life expectancy for a 40-year-old individual.
      RESULTS: In the optimum scenario, cumulative incidence prevented over a period of
      20 years was 240,000 cases for acute myocardial infarction, or 30% of the
      expected number of cases, 328,000 (16%) for other coronary heart disease and
      215,000 (21%) for stroke. For the moderate improvement scenario, the
      corresponding figures were 119,000 (14%), 163 000 (8%) and 105,000 (10%),
      respectively. The individual contributions of each of the separate dietary
      factors were greatest for fish, followed in decreasing order by fruit,
      vegetables, saturated and trans fatty acids. Only fish and fruit contributed to a
      decrease in strokes. In the optimum scenario, 1 year was added to the life
      expectancy of a 40-year-old individual and half a year in the moderate
      improvement scenario. CONCLUSION: Broader adherence to recommendations for daily
      intake of fruit, vegetables, fish and fatty acid composition may take away as
      much as 20-30% of the burden of cardiovascular disease and result in
      approximately 1 extra life year for a 40-year-old individual. Promotion of a
      healthy diet should be given more emphasis in the prevention of cardiovascular
      disease.

PMID- 19593153
TI  - Epidemiologic evidence on mobile phones and tumor risk: a review.
AB  - This review summarizes and interprets epidemiologic evidence bearing on a
      possible causal relation between radiofrequency field exposure from mobile phone
      use and tumor risk. In the last few years, epidemiologic evidence on mobile phone
      use and the risk of brain and other tumors of the head in adults has grown in
      volume, geographic diversity of study settings, and the amount of data on longer
      term users. However, some key methodologic problems remain, particularly with
      regard to selective nonresponse and inaccuracy and bias in recall of phone use.
      Most studies of glioma show small increased or decreased risks among users,
      although a subset of studies show appreciably elevated risks. We considered
      methodologic features that might explain the deviant results, but found no clear
      explanation. Overall the studies published to date do not demonstrate an
      increased risk within approximately 10 years of use for any tumor of the brain or
      any other head tumor. Despite the methodologic shortcomings and the limited data
      on long latency and long-term use, the available data do not suggest a causal
      association between mobile phone use and fast-growing tumors such as malignant
      glioma in adults (at least for tumors with short induction periods). For slow
      growing tumors such as meningioma and acoustic neuroma, as well as for glioma
      among long-term users, the absence of association reported thus far is less
      conclusive because the observation period has been too short.

PMID- 19593152
TI  - Midlife use of written Japanese and protection from late life dementia.
AB  - BACKGROUND: The cognitive reserve hypothesis would predict that use of written
      Japanese should confer protection against dementia because of the complexity of
      its ideograms compared with written English. We sought to test this hypothesis in
      analyses from a longitudinal study of Japanese-American men. METHODS:
      Participants were second-generation Japanese-American men (Nisei) on the island
      of Oahu, Hawaii, who were seen in 1965 and in subsequent examinations to detect
      dementia beginning in 1991-1993. Use of spoken and written Japanese was self
      reported in 1965 (Analyses 1 and 2), and midlife use of written Japanese and
      written English was self-reported in 1994-1996 (Analysis 3). We analyzed
      prevalent dementia outcomes in 1991-1993 (Analysis 1, n = 3139) using logistic
      regression, and incident dementia outcomes in 1994-2002 (Analysis 2, n = 2299)
      and in 1997-2002 (Analysis 3, n = 1655) using Cox proportional hazards
      regression. Dementia outcomes included all-cause dementia, probable and possible
      Alzheimer disease, and probable vascular dementia. We adjusted models for
      probable and possible confounders. RESULTS: Participants who reported proficiency
      with written Japanese were older and had lower incomes. For Analysis 1, there
      were 154 prevalent cases of dementia, 74 of Alzheimer disease, and 43 of vascular
      dementia; for Analysis 2, 236 incident cases of dementia, 138 of Alzheimer
      disease, and 45 of vascular dementia; and for Analysis 3, 125 incident cases of
      dementia, 80 of Alzheimer disease, and 20 of vascular dementia. There was no
      relationship in adjusted models between self-reported proficiency with written
      Japanese and any dementia outcomes. CONCLUSIONS: Proficiency with written
      Japanese does not appear to be protective for dementia.

PMID- 19593154
TI  - The origin and spread of a mumps epidemic: United kingdom, 2003-2006.
AB  - BACKGROUND: The United Kingdom (UK) underwent a massive epidemic of mumps from
      2003 through 2006. The origin and spread was mapped in 350 general practices that
      used office computers to contribute comprehensive medical information on
      approximately 3 million patients to the General Practice Research Database
      (GPRD). METHODS: The continuous 3-month cumulative incidence of mumps (2003-2006)
      was estimated by dividing the number of diagnosed cases of mumps each 3 months by
      the population at risk according to age, region, practice, and calendar time. The
      effect of the measles, mumps, and rubella (MMR) vaccine was estimated by
      comparing vaccine exposure of those diagnosed with mumps and those who were not.
      RESULTS: There were 5683 cases of mumps recorded in the Database over the 4-year
      time period. As the Database represents about 5% of the UK population, we
      estimate that there were more than 100,000 cases of mumps diagnosed in the UK
      during these 4 years. The epidemic appears to have started in one practice in
      Wales in the first 6 months of 2003 and then spread slowly north and east,
      reaching a peak in 2005. Young adults aged 18-24 years were at the highest risk.
      There were 3 major MMR vaccination campaigns (1988-1989, 1997, and 2004-2005)
      that by 2006 provided more than 70% protection against mumps in children younger
      than 18 years of age. Protection was higher in those who had received 2 doses of
      the vaccine. CONCLUSION: A comprehensive program of medical information generated
      by selected general practitioners has provided a sound basis for the real-time
      recording of the origin, spread, and scope of an infectious disease.

PMID- 19593155
TI  - Extreme high temperatures and hospital admissions for respiratory and
      cardiovascular diseases.
AB  - BACKGROUND: Although the association of high temperatures with mortality is well
      documented, the association with morbidity has seldom been examined. We assessed
      the potential impact of hot weather on hospital admissions due to cardiovascular
      and respiratory diseases in New York City. We also explored whether the weather
      disease relationship varies with socio-demographic variables. METHOD: We
      investigated effects of temperature and humidity on health by linking the daily
      cardiovascular and respiratory hospitalization counts with meteorologic
      conditions during summer, 1991-2004. We used daily mean temperature, mean
      apparent temperature, and 3-day moving average of apparent temperature as the
      exposure indicators. Threshold effects for health risks of meteorologic
      conditions were assessed by log-linear threshold models, after controlling for
      ozone, day of week, holidays, and long-term trend. Stratified analyses were used
      to evaluate temperature-demographic interactions. RESULTS: For all 3 exposure
      indicators, each degree C above the threshold of the temperature-health effect
      curve (29 degrees C-36 degrees C) was associated with a 2.7%-3.1% increase in
      same-day hospitalizations due to respiratory diseases, and an increase of 1.4%
      3.6% in lagged hospitalizations due to cardiovascular diseases. These increases
      for respiratory admissions were greater for Hispanic persons (6.1%/ degrees C)
      and the elderly (4.7%/ degrees C). At high temperatures, admission rates
      increased for chronic airway obstruction, asthma, ischemic heart disease, and
      cardiac dysrhythmias, but decreased for hypertension and heart failure.
      CONCLUSIONS: Extreme high temperature appears to increase hospital admissions for
      cardiovascular and respiratory disorders in New York City. Elderly and Hispanic
      residents may be particularly vulnerable to the temperature effects on
      respiratory illnesses.

PMID- 19593157
TI  - Measurement of physical performance and objective fatigability in people with
      mild-to-moderate traumatic brain injury.
AB  - The aims of this study were to objectively measure the physical performance and
      physical endurance of patients with traumatic brain injury with minimization of
      cognitive and psychological fatigue, and to compare the physical performance of
      brain injured patients with that of healthy controls. This was a nonrandomized
      partially blinded controlled study. The study setting was the Outpatient
      Multidisciplinary Brain Injury Clinic in the Department of Physical Medicine and
      Rehabilitation of a tertiary care university teaching hospital. Participants
      included an experimental group that comprised independently ambulant men (age 18
      55 years) with mild-to-moderate traumatic brain injury (n = 24) who complained of
      greater fatigue than before their injury and an age-matched and sex-matched
      control group (n = 24). The intervention included the Six-Minute Walk Test. The
      primary outcome measures were the Six-Minute Walk Distance, the Fatigue Severity
      Scale, Addenbrooke's Cognitive Examination, and the Fatigue Visual Numeric Scale;
      the secondary outcome measures were the Physiological Cost Index of Walking and
      the Borg Scale of Perceived Exertion. The Six-Minute Walk Distance of the
      experimental group (452.33+/-68.816) when compared with that of the control group
      (518.08+/-92.114) was reduced by 12.7 and 30.5%, respectively, when compared with
      the predicted Six-Minute Walking Distance (650.04+/-79.142) for the same age and
      sex. The mean Fatigue Severity Scale values were 2.51 and 1.62 for the
      experimental and control groups, respectively. The mean Addenbrooke's Cognitive
      Examination Score for the patients was 85.5+/-7.265. In conclusion, the Six
      Minute Walk Test is useful in segregating physical fatigue from cognitive and
      psychological aspects of fatigue when cognitive and psychological dimensions are
      known. The Six-Minute Walk Test can be used as a tool for exercise intensity
      prescription in men with mild-to-moderate brain injury, to avoid the deleterious
      effects of fatigue.

PMID- 19593156
TI  - Choline and risk of neural tube defects in a folate-fortified population.
AB  - BACKGROUND: Folic acid is known to reduce risk of neural tube defects (NTDs).
      Even so, NTDs continue to occur despite individual supplementation or population
      fortification with folic acid. We investigated other nutrients related to one
      carbon metabolism that may affect NTD risk. METHODS: This prospective study
      included data from more than 180,000 pregnant women in California from 2003
      through 2005. Midpregnancy serum specimens were linked with delivery information
      regarding the presence of a NTD, another structural malformation, or no
      malformation in the fetus. We identified 80 NTD-affected pregnancies (cases) and
      we randomly selected 409 pregnancy controls. Serum specimens were tested for
      methylmalonic acid, homocysteine, cysteine, methionine, total choline, betaine,
      cystathionine, vitamin B6, folate, vitamin B12, riboflavin, and creatinine.
      RESULTS: We observed elevated NTD risks associated with lower levels of total
      choline, and reduced risks with higher levels of choline. Specifically, we
      observed an odds ratio of 2.4 (95% confidence interval = 1.3-4.7) associated with
      the lowest decile and an odds ratio of 0.14 (0.02-1.0) associated with the
      highest decile, both relative to the 25th-74th percentiles of the control
      distribution. These data did not show meaningful differences between cases and
      controls for any other analytes. CONCLUSIONS: This is the first study to
      investigate total choline in NTD-affected pregnancies. Our findings for choline,
      for which low levels were a risk factor and higher levels were a protective
      factor for NTDs, may offer a useful clue toward understanding the complex
      etiologies of NTDs in an era of folic acid fortification of the food supply.

PMID- 19593158
TI  - Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with
      response and remission in a sample of depressive patients.
AB  - Cytochrome P450 genes are involved in the metabolism of antidepressants and could
      influence treatment response. The aim of this study was to investigate the role
      of allelic variations of the cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6
      genes in antidepressant treatment response and remission rates. Two hundred and
      seventy-eight patients affected by major depression, responders (N = 81) and
      nonresponders (N=197) to at least one adequate antidepressant treatment, were
      recruited with a multicentre design for resistant depression and genotyped for
      all relevant variations. None of the considered metabolic profiles (e.g. poor,
      intermediate, extensive and ultrarapid metabolizers) was found to be associated
      with either response or remission rates. In conclusion, the investigated
      cytochrome genes do not seem to play a major role in antidepressant response in
      the present sample of depressive patients. Nevertheless, methodological and
      sample size limitations of this study do not allow definitive conclusions.

PMID- 19593159
TI  - Efavirenz dose reduction is safe in patients with high plasma concentrations and
      may prevent efavirenz discontinuations.
AB  - OBJECTIVE: To establish whether efavirenz dose reduction in patients with high
      plasma concentrations prevents toxicity-induced efavirenz discontinuations.
      METHODS: HIV-infected patients with a high efavirenz plasma concentration
      (>or=4.0 mg/L) while using efavirenz 600 mg once daily as part of their highly
      active antiretroviral therapy regimen were selected from the AIDS Therapy
      Evaluation in The Netherlands cohort study. These patients were classified into 2
      groups. The reduced-dose group contained all patients who underwent dose
      reduction after the high plasma concentration measurement; the standard-dose
      group consisted of patients who had no dose reduction. Kaplan-Meier and Cox
      proportional hazards analysis were used to assess the impact of dose reduction on
      toxicity-induced efavirenz discontinuations. RESULTS: One hundred eighty patients
      with high plasma efavirenz levels were included, 47 of them subsequently had
      their efavirenz dose reduced from 600 mg to 400 mg once-daily, which resulted in
      a 41% decrease in the median efavirenz plasma concentration. At week 48, the
      Kaplan-Meier estimated cumulative incidence of toxicity-induced efavirenz
      discontinuations was 11.5% in patients who continued the standard dose versus
      2.3% in patients who had a dose reduction; P = 0.066 (log-rank test). Dose
      reduction was not associated with loss of virological suppression. CONCLUSIONS:
      Dose reduction may prevent toxicity-induced discontinuations in patients with
      high efavirenz plasma concentrations, whereas not compromising virological
      efficacy.

PMID- 19593161
TI  - Transcranial color Doppler is essential to quantify right-to-left shunt severity.

PMID- 19593162
TI  - Inflammatory substrate with eosinophils may be present in bare-metal stent
      thrombosis.
AB  - Coronary stent thrombosis is a rare but life-threatening event after percutaneous
      revascularization. We report an in-vivo documentation of the pathologic process
      in the setting of a very late thrombosis within a bare-metal stent, showing
      eosinophil infiltrates. Interestingly, our case indicates that eosinophil
      infiltrates might not be a peculiarity of late drug-eluting stent thrombosis.

PMID- 19593160
TI  - Specific transduction of HIV-susceptible cells for CCR5 knockdown and resistance
      to HIV infection: a novel method for targeted gene therapy and intracellular
      immunization.
AB  - HIV-1 gene therapy offers a promising alternative to small molecule
      antiretroviral treatments and current vaccination strategies by transferring,
      into HIV-1-susceptible cells, the genetic ability to resist infection. The need
      for novel and innovative strategies to prevent and treat HIV-1 infection is
      critical due to devastating effects of the virus in developing countries, high
      cost, toxicity, generation of escape mutants from antiretroviral therapies, and
      the failure of past and current vaccination efforts. As a first step toward
      achieving this goal, an HIV-1-susceptible cell-specific targeting vector was
      evaluated to selectively transfer, into CCR5-positive target cells, an anti-HIV
      CCR5 shRNA gene for subsequent knockdown of CCR5 expression and protection from
      HIV-1 infection. Using a ZZ domain/monoclonal antibody-conjugated Sindbis virus
      glycoprotein pseudotyped lentiviral vector, here we demonstrate the utility of
      this strategy for HIV-1 gene therapy by specifically targeting HIV-1-susceptible
      cells and engineering these cells to resist HIV-1 infection. CCR5-positive human
      cells were successfully and specifically targeted in vitro and in vivo for
      transduction by a lentiviral vector expressing a highly potent CCR5 shRNA which
      conferred resistance to HIV-1 infection. Here we report the initial evaluation of
      this targeting vector for HIV-1 gene therapy in a preexposure prophylactic
      setting.

PMID- 19593163
TI  - Clostridium difficile-associated small bowel enteritis after total
      proctocolectomy in a Crohn's disease patient.

PMID- 19593164
TI  - Utilization of platelet count spleen diameter ratio in predicting the presence of
      esophageal varices in patients with cirrhosis.
AB  - GOALS: To assess whether the platelet count/spleen diameter ratio is a useful
      noninvasive predictor of esophageal varices. BACKGROUND: Current guidelines
      recommend that all patients with cirrhosis undergo screening endoscopy for the
      presence of varices. Recent studies have focused on using noninvasive techniques
      to stratify cirrhotic patients according to their risk of having varices. One
      study examining the platelet count/spleen diameter ratio using a cut-off value of
      909, yielded a negative predictive value of 100% for the presence of varices.
      STUDY: A retrospective analysis of 137 patients with cirrhosis over the age of 18
      that underwent screening endoscopy for varices between January 2003 and October
      2005. The data collected were age, sex, etiology of cirrhosis, spleen diameter,
      prothrombin time/international normalized ratio, total bilirubin, platelet count,
      albumin, Child-Pugh score, and endoscopic findings. RESULTS: There were 137
      patients with 87 (63.5%) men and a mean age of 56 years. Seventy-six (55%)
      patients had esophageal varices. The mean age, sex, and etiology of cirrhosis
      were similar between those with and without varices. Using a platelet
      count/spleen diameter ratio with a cut-off value of 909, yielded a negative
      predictive value of only 73% and a positive predictive value of 74%. CONCLUSIONS:
      The platelet count/spleen diameter ratio with a cut-off value of 909 may not be
      sufficiently accurate in predicting the presence of esophageal varices. Upper
      endoscopy remains the method of choice to screen for the presence of varices.

PMID- 19593165
TI  - Adalimumab-induced autoimmune hepatitis.
AB  - Antitumor necrosis factor antibodies are widely used in the treatment of
      autoimmune diseases. We describe the occurrence of autoimmune hepatitis in a
      patient treated with adalimumab, a fully human IgG antibody against tumor
      necrosis factor, for psoriatic arthritis. The patient made a full recovery after
      discontinuation of adalimumab and treatment with steroids. This is the first
      reported case of adalimumab-induced autoimmune hepatitis.

PMID- 19593166
TI  - Association of SPINK1 gene mutation and CFTR gene polymorphisms in patients with
      pancreas divisum presenting with idiopathic pancreatitis.
AB  - BACKGROUND: Pancreas divisum has been associated with idiopathic pancreatitis.
      However, the causal association remains controversial. OBJECTIVE: To study the
      gene mutations in patients with pancreas divisum presenting with idiopathic
      pancreatitis. METHODS: All consecutive patients with pancreas divisum presenting
      with recurrent pancreatitis were included in the study. Fifty healthy volunteers,
      30 patients with chronic pancreatitis, and 14 patients with idiopathic recurrent
      acute pancreatitis without pancreas divisum served as controls. Patients and
      controls were tested for cationic trypsiongen gene, CFTR gene and SPINK1 gene
      mutations. RESULTS: Of the 12 patients with pancreas divisum and idiopathic
      pancreatitis, 4 had SPINK1 N34S gene mutation-3 were heterozygous and 1 was
      homozygous, and 1 had P55S mutation compared with 1 of 50 healthy controls with
      N34S mutation (P=0.001). The frequency of SPINK1 mutation was similar among
      patients with pancreas divisum and pancreatitis (41.6%), chronic pancreatitis
      (43.3%), and recurrent acute pancreatitis without pancreas divisum (35.7%). Five
      patients with pancreas divisum had polymorphisms in the CFTR gene. CONCLUSION:
      Patients with pancreas divisum presenting with idiopathic pancreatitis had a
      higher frequency of SPINK1 gene mutation compared with healthy controls, which
      might be responsible as the sole-factor or a co-factor in causing pancreatitis in
      them.

PMID- 19593167
TI  - Antidepressants as hydrobromide salts: are they a cause for concern?

PMID- 19593168
TI  - ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine.
AB  - To examine the genetic factors influencing clozapine kinetics in vivo, 75
      patients treated with clozapine were genotyped for CYPs and ABCB1 polymorphisms
      and phenotyped for CYP1A2 and CYP3A activity. CYP1A2 activity and dose-corrected
      trough steady-state plasma concentrations of clozapine correlated significantly
      (r = -0.61; P = 1 x 10), with no influence of the CYP1A2*1F genotype (P = 0.38).
      CYP2C19 poor metabolizers (*2/*2 genotype) had 2.3-fold higher (P = 0.036)
      clozapine concentrations than the extensive metabolizers (non-*2/*2). In patients
      comedicated with fluvoxamine, a strong CYP1A2 inhibitor, clozapine and
      norclozapine concentrations correlate with CYP3A activity (r = 0.44, P = 0.075; r
      = 0.63, P = 0.007, respectively). Carriers of the ABCB1 3435TT genotype had a 1.6
      fold higher clozapine plasma concentrations than noncarriers (P = 0.046). In
      conclusion, this study has shown for the first time a significant in vivo role of
      CYP2C19 and the P-gp transporter in the pharmacokinetics of clozapine. CYP1A2 is
      the main CYP isoform involved in clozapine metabolism, with CYP2C19 contributing
      moderately, and CYP3A4 contributing only in patients with reduced CYP1A2
      activity. In addition, ABCB1, but not CYP2B6, CYP2C9, CYP2D6, CYP3A5, nor CYP3A7
      polymorphisms, influence clozapine pharmacokinetics.

PMID- 19593170
TI  - Efficacy of an algorithm-guided treatment compared with treatment as usual: a
      randomized, controlled study of inpatients with depression.
AB  - OBJECTIVE: Medication algorithms have been proposed as effective means to offer
      optimal treatment and improved outcome for patients with severe mental illness.
      This single-center prospective study compared the efficacy and effects on
      treatment prescriptions of an algorithm-guided treatment regimen with treatment
      as usual (TAU) in depressed inpatients. METHODS: Depressed inpatient participants
      were randomized to an algorithm-guided standardized stepwise drug treatment
      regimen (SSTR, n = 74) or TAU (n = 74). The SSTR regimen included sleep
      deprivation, antidepressant monotherapy, lithium augmentation, monoamine oxidase
      inhibitor therapy, or electroconvulsive therapy guided by scores on the clinician
      rated Bech-Rafaelsen Melancholia Scale. The primary outcome was time to remission
      (defined as a Bech-Rafaelsen Melancholia Scale score of < or =7). Secondary
      outcomes were remission rates, number of changes in treatment strategies (types),
      and the number of different prescribed medications over the treatment period.
      RESULTS: Patients receiving SSTR had a significantly shorter time to remission
      (7.0 +/- 0.9 weeks vs 12.3 +/- 1.8 weeks for TAU). Compared with that in
      remitters in SSTR, the number of strategy changes was significantly higher in TAU
      remitters (3.0 +/- 2.7 and 1.0 +/- 1.5) and had more psychotropic medications
      (fix agents: 3.0 +/- 1.5 and 1.9 +/- 1.1; optional agents: 1.5 +/- 1.0 and 0.9 +/
      0.7). Although more patients dropped out of the SSTR group (33 of SSTR, 12 of
      TAU), the probability of remission tended to be higher in SSTR. CONCLUSIONS:
      Algorithm-guided treatment produces better outcomes and less frequent medication
      changes than TAU. A systematic, stepwise, measurement-based approach to the
      treatment of depressed inpatients is warranted.

PMID- 19593171
TI  - Efficacy of a combination of flumazenil and gabapentin in the treatment of
      alcohol dependence: relationship to alcohol withdrawal symptoms.
AB  - Improved treatment of alcohol dependence is a high priority, including defining
      subtypes that might respond differently. We evaluated a medication combination of
      intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and
      did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol
      dependent individuals (44 with low AW and 16 with high AW) were randomized to
      receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and
      GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol
      withdrawal was measured for the first 2 days, and drinking, sleep parameters, and
      adverse events were monitored during weekly evaluations, along with behavioral
      counseling sessions. Percent days abstinent (PDA) during treatment and time to
      first heavy drinking (TFHD) day were primary outcome variables. There was an
      interaction between the pretreatment AW status and the medication group on PDA (P
      = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more
      TFHD if treated with active medications, whereas those in the low AW group had
      more PDA and more TFHD if treated with placebo. This interaction remained for
      those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate
      deficient transferrin values. In addition, the pattern of response remained up to
      8 weeks after treatment. In addition, in those with high AW, greater improvement
      in AW symptoms was observed in the active medication group compared with the
      placebo group. These results suggest a differential response to FMZ/GBP
      treatment, depending on pretreatment AW status that should be taken into account
      during future treatment trials.

PMID- 19593173
TI  - Artificial neural network model for the prediction of obsessive-compulsive
      disorder treatment response.
AB  - Several patients with obsessive-compulsive disorder (OCD) who are refractory to
      adequate treatment with first-line treatments are considered treatment-resistant.
      Further surveys were to be implemented to explore the outcome predictors of the
      antiobsessional response. Such study was aimed at building a model suitable to
      predict the final outcome of a mixed OCD pharmacologic and nonpharmacologic
      treatment approaches. We studied 130 subjects with OCD who underwent
      pharmacologic (with selective serotonin reuptake inhibitors alone or with
      selective serotonin reuptake inhibitors and risperidone at low dosage) and/or
      behavioral therapy (using exposure and response prevention techniques). The
      following variables were used as predictors: symptoms dimension, as resulting
      from the Yale-Brown Obsessive-Compulsive Scale items factor analysis;
      neuropsychologic performances; and epidemiologic variables. The treatment
      response arising from 3 to 6 months of therapy was used as dependent variable. A
      conventional logistic regression was used to define a previsional model of
      treatment response and multilayer perceptrons and to supervise an artificial
      neural network technique. The 46.9% of the sample resulted to be refractory to
      treatment. Results obtained with the logistic regression model showed that the
      only predictors of treatment outcome are hoarding symptoms, repeating rituals,
      and counting compulsions. Furthermore, using all the variables considered in the
      models, multilayer perceptrons showed highly better predictive performance as
      compared with the logistic regression models (93.3% vs 61.5%, respectively, of
      correct classification of cases). Complex interactions between different clinical
      and neuropsychologic variables are involved in defining OCD treatment response
      profile, and nonlinear and interactive modeling strategies, that is, supervised
      artificial neural networks, seem to be more suitable to investigate this
      complexity than linear techniques.

PMID- 19593174
TI  - Targeted naltrexone for problem drinkers.
AB  - This study aimed to replicate and extend prior research showing that the targeted
      use of naltrexone is a useful strategy to reduce heavy drinking. We compared the
      effects of naltrexone with those of placebo in a sample of 163 individuals (58.3%
      male) whose goal was to reduce their drinking to safe limits. Patients received
      study medication (ie, naltrexone 50 mg or placebo) and were instructed to use it
      daily or targeted to situations identified by them as being high risk for heavy
      drinking. An interactive voice response system was used to obtain daily reports
      of drinking and medication use during the 12-week trial. Analyses were conducted
      using hierarchical linear modeling, with sex as a potential moderator variable.
      On the primary outcome measure, mean drinks per day, at week 12, men in the
      targeted naltrexone group drank significantly less than patients in the other
      groups did. On a secondary outcome measure, drinks per drinking day, during week
      12, the targeted naltrexone group drank significantly less than the other groups
      did, with no moderating effect of sex. These results support the use of a
      targeted approach to reduce drinking among heavy drinkers, particularly men, but
      argue for the use of additional strategies or more efficacious medications than
      naltrexone to increase the effects of such an intervention.

PMID- 19593175
TI  - Effectiveness and safety of the combination of fluoxetine and olanzapine in
      outpatients with bipolar depression: an open-label, randomized, flexible-dose
      study in Puerto Rico.
AB  - We studied the effectiveness of olanzapine/fluoxetine combination (OFC) treatment
      of bipolar depressive episode (7 weeks, study period 1 [SP1]). Study period 1
      responders (mean modal daily OFC dosage, 10.8/27.8 mg) were randomized to OFC
      continuation treatment or olanzapine (OLZ) monotherapy starting at 10 mg (12
      weeks, SP2). Seventy-three percent of the 114 patients who entered into SP2
      completed the trial. The Montgomery-Asberg Depression Rating Scale total score
      changes from baseline in SP1 (primary outcome) were significant (-20 +/- 10, P <
      0.001) and, during SP2, worsened for patients in the OLZ group (OFC vs OLZ, -0.4
      +/- 7.55 vs +8.2 +/- 14.1, respectively; P < 0.001). During SP1, 69% responded
      and 59% remitted. During SP2, significantly more patients in the OFC group
      maintained response (31.3% vs 12.5%) and remission (71.4% vs 39.6%) than patients
      in the OLZ group. Treatment-emergent adverse events with OFC (SP1 and SP2)
      included increased appetite, increased weight, somnolence, anxiety, insomnia, and
      depressed mood. Since visit 1, the mean weight increases (in pounds) were 4.8 +/-
      6.8 for SP1 (P < 0.001) and 6.3 +/- 10.3 (OFC) or 10.7 +/- 11.3 (OLZ) for SP2;
      50% (OLZ) and 33% (OFC) of the patients had a 7% or higher weight increase. For
      cholesterol, triglycerides, and low-density lipoprotein levels and some hepatic
      enzymes, there were statistically and clinically significant changes in both
      study periods but no differences between the SP2 groups. Study limitations
      included the open-label design and exclusion of the SP1 nonresponders from SP2.
      These study results suggest that improvements resulting from 7 weeks of acute OFC
      treatment of a bipolar depressive episode are maintained in responders for an
      additional 12 weeks with OFC, but switching to OLZ alone may result in symptom
      worsening.

PMID- 19593177
TI  - Mean platelet volume in patients with major depression: effect of escitalopram
      treatment.
AB  - BACKGROUND: The relationship between major depression and increased platelet
      activity has been previously indicated by several studies. The aims of this study
      were to examine mean platelet volume (MPV), which is an indicator of platelet
      activity, in patients with depression and investigate whether escitalopram
      treatment would affect MPV. METHODS: Fifteen patients (11 women and 4 men)
      meeting the criteria for a current episode of major depressive disorder were
      recruited to the study and 17 physically and mentally healthy comparison subjects
      (11 women and 6 men). Mean platelet volume and platelet count of the controls and
      patients were measured upon entry to the study. After 8 weeks of open-label
      treatment with the selective serotonin reuptake inhibitor escitalopram (10-20
      mg/d), the patients with depression were readmitted and the measurements were
      repeated. RESULTS: At baseline, in comparison with the control group, the group
      with depression exhibited greater platelet activity as detected by increased MPV.
      After escitalopram treatment, the patients with depression exhibited significant
      reduction in MPV. There was also a significant decline in platelet count.
      CONCLUSIONS: In this study, normalization of platelet activation is associated
      with escitalopram treatment for patients with depression. This finding may
      provide evidence for the use of escitalopram in patients with major depression
      and comorbid ischemic heart disease.

PMID- 19593176
TI  - Metabolic assessment of aripiprazole as adjunctive therapy in major depressive
      disorder: a pooled analysis of 2 studies.
AB  - In 2 identical multicenter, double-blind, placebo-controlled trials, an 8-week
      prospective treatment phase to ensure inadequate response to standard
      antidepressants was followed with 6 weeks of aripiprazole (2-20 mg/d) or placebo,
      plus a standard antidepressant. This pooled analysis involving 737 patients
      across the 2 studies evaluated the metabolic effects of adjunctive aripiprazole
      in patients with major depressive disorder. Outcomes included mean change from
      end of prospective treatment phase to endpoint in body weight, waist
      circumference, fasting levels of total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting
      plasma glucose, and glycosylated hemoglobin (hemoglobin A1C). Logistic regression
      determined whether baseline variables were associated with weight gain or whether
      weight change was associated with clinical outcome. Statistically significant
      increases occurred in mean body weight (adjunctive aripiprazole, +1.73 kg, vs
      adjunctive placebo, +0.38 kg; P < 0.001). Significantly more subjects receiving
      adjunctive aripiprazole had clinically relevant (> or = 7%) weight gain versus
      placebo (5.2% vs 0.6%; P < 0.001). More patients treated with adjunctive
      aripiprazole shifted body mass index category group from normal to overweight and
      from overweight to obese than those treated with adjunctive placebo. Body mass
      index, sex, age, Montgomery-Asberg Depression Rating Scale score, fasting TG,
      fasting glucose, and standard antidepressants were not clinically meaningful
      predictors of weight gain with adjunctive aripiprazole, and change in weight had
      no correlation with clinical outcome. Adjunctive aripiprazole produced no
      significant changes versus placebo in mean waist circumference, total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, TG, fasting plasma glucose, or hemoglobin A1C. Also, there was no
      apparent change in the incidence of National Cholesterol Education Program
      defined abnormal metabolic measures after treatment with aripiprazole.

PMID- 19593178
TI  - Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and
      the placebo response in major depressive disorder.
AB  - The placebo response shows pronounced interindividual variability. Placebos are
      postulated to act through central reward pathways that are modulated by
      monoamines. Because monoaminergic signaling is under strong genetic control, we
      hypothesized that common functional polymorphisms modulating monoaminergic tone
      would be related to degree of improvement during placebo treatment of subjects
      with major depressive disorder. We examined polymorphisms in genes encoding the
      catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects
      with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest
      activity form of the enzyme (G or G/G) had a significantly lower magnitude of
      placebo response than those with other genotypes. Subjects with ValMet catechol-O
      methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2
      Met alleles) showed a statistical trend toward a lower magnitude of placebo
      response. These findings support the hypothesis that genetic polymorphisms
      modulating monoaminergic tone are related to degree of placebo responsiveness in
      major depressive disorder.

PMID- 19593179
TI  - A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita
      (chamomile) extract therapy for generalized anxiety disorder.
AB  - OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled efficacy
      and tolerability trial of Matricaria recutita (chamomile) extract therapy in
      patients with mild to moderate generalized anxiety disorder (GAD). We
      hypothesized that chamomile would be superior to placebo in reducing GAD symptoms
      with a comparable tolerability profile. MATERIALS AND METHODS: Sixty-one
      outpatients with mild to moderate GAD were enrolled, and 57 were randomized to
      either double-blind chamomile extract (n = 28) or placebo therapy (n = 29) for 8
      weeks. The study was powered to detect a statistically significant and clinically
      meaningful group difference in change over time in total Hamilton Anxiety Rating
      (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory,
      Psychological Well Being, and Clinical Global Impression Severity scores and the
      proportion of patients with 50% reduction or more in baseline HAM-A score.
      RESULTS: We observed a significantly greater reduction in mean total HAM-A score
      during chamomile versus placebo therapy (P = 0.047). Although the study was not
      powered to identify small to moderate differences in secondary outcomes, we
      observed a positive change in all secondary outcomes in the same direction as the
      primary outcome measure. One patient in each treatment group discontinued therapy
      for adverse events. The proportion of patients experiencing 0, 1, 2, or 3 adverse
      events or more was not significantly different between groups (P = 0.417).
      CONCLUSIONS: This is the first controlled clinical trial of chamomile extract for
      GAD. The results suggest that chamomile may have modest anxiolytic activity in
      patients with mild to moderate GAD. Future studies are needed to replicate these
      observations.

PMID- 19593180
TI  - Venlafaxine metabolism as a marker of cytochrome P450 enzyme 2D6 metabolizer
      status.
AB  - INTRODUCTION: One of the major enzymes of the cytochrome P450 drug-metabolizing
      system, CYP2D6, shows a high degree of genetic polymorphism and variability in
      activity. Based on the degree of CYP2D6 activity, individuals can be broadly
      classified as poor metabolizers (PMs) or extensive metabolizers (EMs); the
      metabolism of CYP2D6 substrates differs among PMs and EMs. The metabolism of
      various drugs that are substrates of CYP2D6 has been used as a marker for
      metabolic phenotype, calculating the plasma or urinary metabolic ratio of the
      parent compound to its metabolite. The current analysis evaluates the use of the
      O-desmethylvenlafaxine-venlafaxine ratio (ODV/VEN) after administration of VEN, a
      CYP2D6 substrate, for determining CYP2D6 metabolic phenotype in healthy adults
      receiving VEN. METHODS: The analysis included data from 2 studies in which
      healthy adults were classified as either EMs or PMs using established methods (1
      genotypic and 1 phenotypic) and were then administered VEN at daily dosages
      ranging from 75 to 150 mg. Blood plasma samples were taken at various time
      points, and the ODV/VEN ratio was calculated. RESULTS: Blood samples from 28
      participants in the 2 studies were available for analysis. The ODV/VEN ratio
      distinguished the EM and PM phenotypes; ratios were 1 or greater for EMs and less
      than 1 for PMs at 4 hours after dose administration. CONCLUSIONS: The ratio of
      ODV/VEN is an effective means of phenotyping individuals according to their
      CYP2D6 metabolizer status.

PMID- 19593181
TI  - Smell identification test as a treatment response marker in patients with
      Alzheimer disease receiving donepezil.
AB  - BACKGROUND: Olfactory dysfunction, impaired odor identification in particular, is
      known to occur in Alzheimer disease (AD). The entorhinal cortex and the olfactory
      bulb, critical areas for olfactory function, are rich in acetylcholine, the
      neurotransmitter implicated in AD pathology and treatment. In view of the common
      anatomical substrate, we aimed to determine whether performance on an olfaction
      test can be used as a clinical marker for monitoring the efficacy of donepezil in
      elderly people with AD. METHODS: Twenty-five participants with mild to moderate
      AD, planned for donepezil treatment, were recruited from mental health services
      for older adults in this open-labeled study. Assessments before commencing
      donepezil included Mini-Mental State Examination, Neuropsychiatric Inventory,
      Bristol Activities of Daily Living, and the University of Pennsylvania Smell
      Identification Test. After 3 months of treatment, the primary outcome measure,
      the Clinician Interview Based Impression of Change plus caregiver input (CIBIC
      plus), was completed, and the baseline assessments were repeated. RESULTS:
      Eighteen patients continued to receive donepezil at follow-up. The CIBIC-plus
      outcome correlated with changes in University of Pennsylvania Smell
      Identification Test and Bristol Activities of Daily Living scores from the
      baseline (r = 0.7, P < 0.01). In addition, it was the change in smell
      identification function after treatment that best predicted CIBIC-plus outcome (P
      < 0.05) on ordinal regression analysis. CONCLUSIONS: Smell identification
      function could be useful as a clinical measure to assess treatment response with
      donepezil in AD. This is a nonblind uncontrolled study, and the outcome indicates
      the need for a controlled study.

PMID- 19593182
TI  - Risperidone-induced hyperamylasemia, hyperlipasemia, and neuroleptic malignant
      syndrome: a case report.

PMID- 19593183
TI  - Reply to comments on "Optimizing early prediction for antipsychotic response in
      schizophrenia".

PMID- 19593184
TI  - Toxic clozapine serum levels during inflammatory reactions.

PMID- 19593185
TI  - Predictors of clinical worsening after a switch to aripiprazole in patients with
      schizophrenia: a 1-year naturalistic follow-up study.

PMID- 19593187
TI  - Rhabdomyolysis following dose increase of clozapine and combination therapy with
      lithium.

PMID- 19593186
TI  - The effects of risperidone on the cognitive performance of individuals with
      schizotypal personality disorder.

PMID- 19593188
TI  - Prevalence of metabolic syndrome in patients with psychotic disorders in the
      Netherlands.

PMID- 19593189
TI  - Valproic acid-induced myopathy in a patient with schizoaffective disorder.

PMID- 19593190
TI  - Allopregnanolone levels before and after selective serotonin reuptake inhibitor
      treatment of premenstrual symptoms.

PMID- 19593191
TI  - Influence of antidepressant use on glycemic control in patients with diabetes
      mellitus: an open-label comparative study.

PMID- 19593192
TI  - Hallucinations associated with modafinil treatment for narcolepsy.

PMID- 19593194
TI  - Response to Shen J, Kobak K, Zhao Y, et al. Use of remote centralized raters via
      live 2-way video ina multicenter clinical trial for schizophrenia. (J Clin
      Psychopharmacol. 2008;28:691-693).

PMID- 19593195
TI  - Clinical antipsychotic trials of intervention effectiveness study: a pragmatic
      trial?

PMID- 19593196
TI  - Comments on "An innovative design to establish proof of concept of the
      antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate
      antagonist, CP-101,606 in patients with treatment-refractory major depressive
      disorder".

PMID- 19593198
TI  - Influence of signal strength on OCT measurements.

PMID- 19593199
TI  - Applanation tonometry versus dynamic contour tonometry in eyes treated with
      latanoprost.
AB  - PURPOSE: To examine the differences between Goldmann Applanation Tonometry (GAT)
      and Dynamic Contour Tonometry (DCT) associated with latanoprost use. METHODS:
      Twenty-four eyes (of 24 patients) treated with latanoprost monotherapy
      (latanoprost group, LG), 11 eyes (of 11 patients) not receiving prostaglandin
      analogs (nonlatanoprost group, NLG), and 20 eyes of 20 nonglaucomatous patients
      (control group, CG) were included. GAT, DCT, measurement of central corneal
      thickness and axial length of the eyeball were performed. The difference between
      GAT and DCT intraocular pressure (dIOP) was calculated. Differences in dIOP among
      LG, NLG, and CG and correlations of dIOP with other clinical parameters were
      examined. RESULTS: dIOP was significantly higher in LG, compared with NLG or CG.
      The correlations of dIOP with axial length of the eyeball were statistically
      significant in the LG but not in NLG or CG. The correlations of dIOP with central
      corneal thickness, patients' age, and duration of latanoprost use (LG) were
      statistically not significant. CONCLUSIONS: The fact that dIOP was significantly
      higher in LG, compared with NLG and CG implies that latanoprost may affect the
      biomechanical properties of the ocular walls.

PMID- 19593200
TI  - Aqueous humor and plasma levels of vascular endothelial growth factor and nitric
      oxide in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
AB  - PURPOSE: To investigate levels of vascular endothelial growth factor (VEGF) and
      nitric oxide (NO) in the aqueous humor and plasma of patients with
      pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG), compared
      with controls. METHODS: This prospective study involved 37 patients with PXS, 15
      with PXG, and 32 control subjects in whom cataract surgery was indicated. Aqueous
      humor and plasma VEGF and NO levels were measured with enzyme-linked
      immunosorbent assay and chemiluminescence methods, respectively. RESULTS: Aqueous
      humor and plasma VEGF concentrations were higher in patients with PXS and PXG
      than in controls (P<0.001). Aqueous humor NO concentrations were higher in
      patients with PXS and PXG than in controls (P<0.05 and P=0.001, respectively).
      Plasma NO concentrations did not differ between the 3 groups. Aqueous humor and
      plasma VEGF and NO levels were not significantly different in patients with PXS
      versus PXG. VEGF and NO levels showed no significant correlation among the 3
      groups (P>0.05). CONCLUSIONS: Elevated aqueous humor VEGF and NO levels and
      plasma VEGF concentrations in eyes with PXS and PXG can be explained by the
      ischemic nature of these disorders. The lack of correlation between VEGF and NO
      levels may indicate impaired downregulation, which may have a role in the
      progression to PXG.

PMID- 19593201
TI  - Surgical outcomes of intravitreal bevacizumab and guarded filtration surgery in
      neovascular glaucoma.
AB  - PURPOSE: To assess the efficacy of preoperative intravitreal bevacizumab with
      guarded filtration surgery and mitomycin C in neovascular glaucoma. MATERIALS AND
      METHODS: In this prospective, noncomparative interventional case series,
      neovascular glaucoma patients who had not responded to or could not receive
      panretinal photocoagulation were recruited. Patients received 1.25 mg of
      intravitreal bevacizumab. If needed, the bevacizumab injection was repeated.
      Patients who could not achieve an intraocular pressure <=21 mm Hg despite
      medications underwent trabeculectomy with mitomycin C. Success defined as
      complete if intraocular pressure was 6 to 21 mm Hg without medication, and
      qualified if intraocular pressure was within above range with glaucoma
      medication. Failure was defined as intraocular pressure <6 or >21 mm Hg despite
      medications or reoperation. RESULTS: Thirty eyes were treated. All patients
      demonstrated complete regression of iris neovascularization with 1 or 2
      intravitreal bevacizumab injections. The mean intraocular pressure was 43.1 +/-
      9.3 and 38.9 +/- 12.5 before and 2 weeks after bevacizumab injection,
      respectively (P<0.003). The intraocular pressure in 3 cases was controlled after
      receiving bevacizumab. In 23 cases that underwent filtering surgery and completed
      at least 6 months of follow-up, the mean preoperative and last visit intraocular
      pressure was 43.3 +/- 10.0 mm Hg and 20.6 +/- 5.4 mm Hg, respectively (P<0.001).
      The qualified success rate was 61% at final visit. Neither the significant
      intraoperative nor postoperative complications were noted. CONCLUSIONS:
      Preoperative intravitreal bevacizumab combined with guarded filtration surgery
      with mitomycin C is a safe and effective method of controlling intraocular
      pressure in neovascular glaucoma.

PMID- 19593202
TI  - Intraocular pressure measurement with the noncontact tonometer through soft
      contact lenses.
AB  - PURPOSE: To assess the accuracy of measuring intraocular pressure (IOP) through a
      soft contact lens (SCL) with different refractive powers using a noncontact
      tonometer (NCT). METHODS: Thirty-two healthy adult volunteers free of glaucoma or
      corneal disease participated in this study. IOP was measured in the right eyes
      without SCLs and with different lens powers, from -3.0 to -12.0 D as measured by
      NCT. IOP of the left eyes was also measured, as an internal control. Corneal
      curvature was measured in both eyes using an autokeratometer. Sixteen volunteers
      wore one brand of SCL (group A) and the other 16 wore a different brand, with 2
      different curvatures (groups B and C). Statistical data were analyzed by SPSS
      using the Wilcoxon signed rank test for comparison of IOP readings and multiple
      linear regression analysis for the relationship among power of contact lenses,
      corneal power, and difference in IOP measurements. RESULTS: The difference in
      mean IOP between eyes without lenses and those with lenses was statistically
      significant in lens with -6.0 D and below in all 3 groups. The decrease in IOP
      significantly correlated with the refractive power of contact lenses in all 3
      groups. The difference in IOP measurements was influenced by the mean K in group
      A but not in group B or C. There was no statistically significant difference in
      the IOP measurements in the left eyes or in the mean K between the right and left
      eyes. CONCLUSIONS: IOP measurement through myopic SCLs by NCT may be inaccurate
      and tends toward underestimation, especially in high myopic lenses. A strong
      relationship exists between IOP reduction and myopic lens power.

PMID- 19593203
TI  - Dark room provocative test and extent of angle closure: an anterior segment OCT
      study.
AB  - PURPOSE: To clarify the risk parameters measured by anterior segment optical
      coherence tomography (AS-OCT) for elevated intraocular pressures (IOP) provoked
      by the darkroom test and to provide recommendations for its clinical usage.
      METHODS: Subjects aged >40 years and whose peripheral anterior chambers were
      <=1/4 corneal thickness were recruited. The anterior segment of the eye was
      imaged in sitting position and under both light and dark conditions and biometry
      was performed using anterior segment optical coherence tomography. The analyzed
      parameters were: (1) central anterior chamber depth (ACD); (2) anterior chamber
      width; (3) pupil diameter; (4) iris curvature; (5) lens thickness; and (6) number
      of meridians with closed angles (NCA). Then the darkroom test was performed and a
      positive provocative test result was defined as a rise in IOP >=8 mm Hg after the
      test. Statistical analyses included: (1) the difference in parameters between
      positive and negative eyes; (2) the association between posttest IOP and the
      parameters; and (3) the difference in parameters between the 2 eyes in subjects
      with the asymmetric results. RESULTS: A total of 70 subjects were recruited. ACD
      (P=0.022), NCA in light (P<0.001), and NCA in dark (P<0.001) were different
      significantly between eyes with positive and negative results. There was a strong
      association between NCA in dark (r=0.755, P<0.001) and the posttest IOP. Among
      subjects with asymmetric results between the 2 eyes, the ACD was shallower and
      the lens thickness was larger in the positive eye. CONCLUSIONS: The posttest IOP
      is determined by the extent of functionally closed angles in the dark. The test
      may be useful in the early diagnosis of primary angle closure. At the same time,
      angle configuration should be evaluated to remove false positive result.

PMID- 19593204
TI  - Simultaneous bilateral angle closure glaucoma in a patient with giant cell
      arteritis.
AB  - PURPOSE: To report a case of bilateral angle closure in a patient with giant cell
      arteritis. DESIGN: Observational case report. METHODS: Review of clinical,
      photographic, and biopsy data of a 53-year-old patient who presented with
      bilateral angle closure glaucoma and was found to have giant cell arteritis.
      RESULTS: A temporal artery biopsy revealed near transmural focal scarring of the
      media with disruption of the internal elastic lamina consistent with giant cell
      arteritis in a patient with bilateral angle closure glaucoma. CONCLUSIONS: Acute
      angle closure glaucoma is a relatively uncommon form of glaucoma and its
      relationship, if any, with giant cell arteritis is unknown. This is the first
      reported case of giant cell arteritis presenting with bilateral acute angle
      closure glaucoma.

PMID- 19593206
TI  - Comment on Efficacy and tolerability of prostaglandin analogs.

PMID- 19593207
TI  - Congenital glaucoma: CYP1B1 mutations in Israeli Bedouin kindreds.
AB  - PURPOSE: To investigate CYP1B1 gene mutations in Arab-Bedouin Israeli patients
      with primary congenital glaucoma (PCG). METHODS: Testing linkage to candidate
      genes using adjacent polymorphic markers and sequencing of genomic DNA samples by
      standard methods. RESULTS: In 9 of 11 unrelated affected Israeli Bedouin
      families, PCG was associated with homozygosity of 3 different CYP1B1 mutations.
      As in Saudi Arabian families, the 3987G>A CYP1B1 substitution accounted for
      approximately 50% of cases. A novel CYP1B1 mutation, 8405G>A, was found in 2
      unrelated families. In 2 consanguineous families, there was no evidence of
      homozygosity or mutations in CYP1B1. CONCLUSIONS: CYP1B1 mutations account for
      the majority of cases of PCG in the Israeli Bedouin population. The most
      frequently found CYP1B1 mutation (3987G>A) in our study is also the commonest
      CYP1B1 mutation in the Saudi Arabian population, in line with the common genetic
      background of both populations. The absence of homozygosity in the CYP1B1 locus
      in the affected individuals in 2 consanguineous inbred families, suggests that
      other genes take part in the causation of congenital glaucomas. This is the first
      study describing the genetic basis of PCG among Israeli Arab-Bedouin individuals,
      in whom the frequency of the disease is the highest in the world. Further similar
      studies based on new diagnosed patients are needed to possibly prevent, screen,
      and treat (antenatal and postnatal) this sight-devastating childhood disease.

PMID- 19593209
TI  - Calcium-sensing receptors modulate renin release in vivo and in vitro in the rat.
AB  - OBJECTIVES: Calcium-sensing receptors (CaSRs) have been localized in the
      juxtaglomerular apparatus where they may contribute to the regulation of renin
      release. In the present study, we investigated the in-vitro and in-vivo effects
      of the calcimimetic R-568 on renin release. METHODS: In vitro, the effect of
      calcimimetics on renin release was assessed by incubating freshly isolated rat
      juxtaglomerular cells with or without R-568 (1 and 10 mumol/l) in serum-free
      medium in the presence or absence of forskolin or CaCl2. In vivo, we measured the
      impact of R-568 (20 ng/min intravenously) on the acute changes in plasma renin
      activity (PRA) induced by either a 90 min infusion of the angiotensin-converting
      enzyme inhibitor captopril, or the beta-receptor agonist isoproterenol, or of a
      vehicle in or after a furosemide challenge in conscious Wistar rats. RESULTS: In
      vitro, R-568 dose-dependently blunted renin release, but also reduced the
      increase in renin due to forskolin (P < 0.01). Both isoproterenol and enalapril
      increased in vivo PRA to 3.1 +/- 0.3 and 3.7 +/- 0.5 ng Ang I/ml per h,
      respectively (P < 0.01), compared with vehicle (1.5 +/- 0.2 ng Ang I/ml per h). R
      568 significantly reduced PRA to 2.1 +/- 0.1 ng/ml per h in isoproterenol-treated
      rats and to 1.6 +/- 0.2 ng/ml per h in enalapril-treated rats (P < 0.05). In low
      salt treated animals, acute infusion of furosemide increased PRA from 8.7 +/- 3.2
      to 18.6 +/- 2.3, whereas R-568 partially blunted this rise to 11.2 +/- 1.5 (P =
      0.02). In vivo, R-568 significantly lowered serum calcium and PTH1-84, but the
      drug-induced changes in PRA were independent of the changes in calcium and
      parathyroid hormone. CONCLUSION: After the recent discovery of CaSRs in
      juxtaglomerular cells of mice, our results confirm the presence of such receptors
      in rats and demonstrate that these receptors modulate renin release both in vitro
      and in vivo. This suggests that CaSRs play a role as a regulatory pathway of
      renin release.

PMID- 19593208
TI  - CYP2C9 genotype modifies activity of the renin-angiotensin-aldosterone system in
      hypertensive men.
AB  - BACKGROUND: Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been
      indicated to have impaired enzyme function, and thus suspected to reduce the
      formation of the active metabolite of losartan. Cytochrome P450 (CYP) enzymes are
      also involved in eicosanoid biosynthesis and regulation of blood pressure (BP)
      and sodium homeostasis. METHODS: We studied the impact of these variants on BP
      response to losartan and three other antihypertensive drugs and on baseline
      indicators of the activity of the renin-angiotensin-aldosterone system. The
      participants were 217 moderately hypertensive Finnish men that participated in
      the double-blind, cross-over, placebo-controlled GENRES Study. RESULTS: BP
      responses to losartan did not differ between CYP2C9*2 or CYP2C9*3 allele carriers
      and CYP2C9*1*1 patients. A suggestive finding of less pronounced ambulatory BP
      response to losartan in CYP2C9*1*3 patients with low-normal kidney function was
      made. At baseline of the GENRES Study, CYP2C9*1*3 patients had significantly
      lower plasma renin activity and aldosterone levels than CYP2C9*1*1 patients (both
      P values 0.004). In a replication study in patients with treatment-resistant
      hypertension, men with CYP2C9*3 allele also had lower plasma renin activity (P =
      0.03) and aldosterone levels (P = 0.18). In addition, these men had attenuated
      renin and aldosterone responses in captopril challenge test (P = 0.29 and 0.006,
      respectively). CONCLUSION: The CYP2C9*3 allele was associated with lower activity
      of the renin-angiotensin-aldosterone system in hypertensive men, which may
      reflect a more efficient sodium reabsorption capacity. CYP2C9*2 and CYP2C9*3
      alleles do not influence the antihypertensive effect of losartan in men with
      essential hypertension and normal kidney function.

PMID- 19593210
TI  - Impairment of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis
      contributes to the acceleration of two-kidney, one-clip Goldblatt hypertension.
AB  - OBJECTIVE: Recent studies have shown that the heptapeptide angiotensin-(1-7) [Ang
      (1-7)] exerts important vasoactive actions and can act as an endogenous
      physiological antagonist of angiotensin II (Ang II) within the renin-angiotensin
      system (RAS). The present study was performed to evaluate the effects, first, of
      chronic increases of Ang-(1-7) levels, second, of [7-D-Ala], an Ang-(1-7)
      receptor antagonist, and, third, of an angiotensin-converting enzyme 2 (ACE2)
      inhibitor on the course of hypertension and of renal function of the nonclipped
      kidney in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. METHODS: Blood
      pressure (BP) was monitored by radiotelemetry. Elevation of the effect of
      circulating Ang-(1-7) levels was achieved either by chronic subcutaneous infusion
      of Ang-(1-7) through osmotic minipumps or by employing transgenic rats that
      express an Ang-(1-7)-producing fusion protein [Ang-(1-7)TGR+/+] (and its control
      Ang-(1-7)TGR-/-). [7-D-Ala] was also infused subcutaneously and the ACE2
      inhibitor was administrated in drinking water. On day 25 after clipping, rats
      were anesthetized and renal function was evaluated. RESULTS: Chronic infusion of
      Ang-(1-7) did not modify the course of 2K1C hypertension and did not alter renal
      function as compared with saline vehicle-infused 2K1C rats. Chronic infusion of
      [7-D-Ala] or treatment with the ACE2 inhibitor worsened the course of
      hypertension and elicited decreases in renal hemodynamics. [Ang-(1-7)TGR+/+] and
      [Ang-(1-7)TGR-/-] rats exhibited a similar course of hypertension. CONCLUSION:
      The present data support the notion that Ang-(1-7) serves as an important
      endogenous vasodilator and natriuretic agent and its deficiency might contribute
      to the acceleration of 2K1C Goldblatt hypertension.

PMID- 19593211
TI  - Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome.
AB  - OBJECTIVE: To test whether a previously hypertension-linked 23 cM region on
      chromosome 2 is linked to the metabolic syndrome (MetS) or its individual
      components, and whether a common I/D polymorphism of the adrenergic receptor 2b
      (ADRA2B) gene, mapping in that region, is associated with the same traits.
      METHODS: We conducted fine mapping of the hypertension-linked region on
      chromosome 2 spanning between 107 and 130 cM using 11 informative polymorphic
      markers in 260 healthy white siblings belonging to 118 nuclear families. Variance
      component linkage analysis was performed for each MetS component and a composite
      sum of MetS phenotypes as quantitative trait after adjustment for significant
      covariates using 'Solar software package'. Successively, the I/D polymorphism of
      the ADRA2B gene was genotyped in 5283 patients in the Malmo Diet and Cancer
      cardiovascular arm, seeking for association with the MetS using standard
      definitions and separately, with its individual components. RESULTS: For 24-h
      pulse pressure and waist/hip ratio, LOD [logarithm of the odds (to the base 10)]
      scores of more than two were found between 107 and 122 cM on chromosome 2. For
      the composite sum of MetS phenotypes, LOD score of more than 1 was found between
      116 and 120 cM. There was no difference between carriers and noncarriers of the D
      allele of the ADRA2B gene in MetS prevalence but D-carriers were associated with
      significantly higher levels of diastolic blood pressure. CONCLUSION: Our results
      suggest that chromosome 2 could harbor one or more genes implied in blood
      pressure homeostasis and MetS development. The ADRA2B I/D polymorphism is not
      consistently associated with MetS and metabolic/anthropometric parameters but
      with diastolic blood pressure in an urban-based population of middle-aged Swedes.

PMID- 19593213
TI  - Relationships between processes and outcomes of nurse practitioners in acute
      care: an exploration.
AB  - This nonexperimental repeated-measure study examined the relationships between
      processes (coordination of care, and provision of counseling and education) and
      outcomes (symptom resolution, functional status, and satisfaction with care)
      expected of acute care nurse practitioners (ACNPs). The data were obtained from
      320 patients admitted to medical, surgical, and cardiac units. The results
      indicated positive association between the process and outcome variables,
      providing initial evidence delineating care processes of ACNPs that contribute to
      the achievement of nursing-sensitive outcomes.

PMID- 19593214
TI  - Clinical outcome of avulsion fracture of the anterior cruciate ligament between
      children and adults.
AB  - The aim of this study was to compare clinical and radiological results after
      surgical treatments of anterior cruciate ligament (ACL) avulsion fractures in
      children and adults. Forty cases (18 children, 22 adults), who underwent surgical
      treatment for an avulsion fracture of the ACL and followed up for more than 1
      year, were enrolled in this study. Fractures were classified using modified
      Meyers and McKeever criteria. We compared the two groups with regard to range of
      motion, Lysholm Knee (LK) scores, the Lachman test and the Pivot-shift test, and
      instrumented anterior laxity determined using an arthrometer. Types of fracture
      in children were categorized as eight cases of type II, 10 of type III; and in
      adults as two cases of type II, 15 of type III, and five of type IV. A higher
      incidence of type IV fracture was encountered in the adult group. Adults had
      higher incidences of accompanied meniscal injuries and type IV fractures than
      children. Significant differences were found in mean LK scores, 99.3 points in
      children and 89.5 in adults (P<0.05). However, no significant differences were
      found between adults and children in terms of range of motion, the Lachman test
      and the Pivot-shift test, and instrumented anterior laxity. LK scores of ACL
      avulsion fracture were better in children than in adults. Possible causes of
      these results are higher incidences of accompanying meniscal injury and type IV
      fracture in adults. However, no intergroup differences were found in terms of
      stabilities.

PMID- 19593215
TI  - Treatment duration of developmental dysplasia of the hip: age and sonography.
AB  - We retrospectively assessed babies treated according to Pavlik's method and
      followed up in our outpatient clinic between the years 2001 and 2005,
      investigating the influence of age at onset of treatment and severity of
      sonographic pathologies on the rates of avascular necrosis and treatment duration
      of 343 pathological hips in 311 neonates. No osteonecrosis was observed at the 1
      year follow-up. Early detection of developmental dysplasia of the hip and early
      initiation of treatment using Pavlik's method are important in preventing
      osteonecrosis, and have high success rates. When using Pavlik's method for
      treating developmental dysplasia of the hip, starting treatment at 13 weeks and
      later increases the duration of treatment.

PMID- 19593212
TI  - Novel genetic variants contributing to left ventricular hypertrophy: the HyperGEN
      study.
AB  - OBJECTIVES: To identify genes contributing to variation in echocardiographic left
      ventricular mass and related traits using linkage and linkage disequilibrium
      analysis in sibships ascertained on hypertension. METHODS: The Hypertension
      Genetic Epidemiology Network (HyperGEN) Study of left ventricular hypertrophy
      characterized left ventricular mass, relative wall thickness (RWT), and aortic
      root diameter (ARD) with echocardiograms collected using a standardized protocol
      at four HyperGEN field centers. A high-throughput scanning fluorescence detector
      system genotyped 387 polymorphisms distributed throughout the genome. Linkage
      analyses were conducted once genotyping results became available for 885 siblings
      from 382 sibships. RESULTS: Although single logarithm of the odds (LOD) score
      peaks of 1.2 or more were found on chromosomes 1, 4, 5, 6, 7, 8, 9, 10, 12, 14,
      17, and 21, we observed a broad band of peaks in both ethnic groups (white and
      black) on chromosome 4 and selected candidate genes (NPY1R, NPY2R, NPY5R, SFRP2,
      CPE, IL15, and EDNRA) from this region. Using cases and controls from extremes of
      the left ventricular mass index, RWT, and ARD distributions, we assessed
      associations with these phenotypes and haplotype-tagging single-nucleotide
      polymorphisms (SNPs) in the candidates. Among blacks, SNPs in IL15, NPY2R, and
      NPY5R showed strong evidence for association (P < 0.005); all candidates except
      EDNRA showed suggestive association (P < 0.05). In whites, NPY2R, NPY5R, and
      SFRP2 SNPs offered suggestive evidence of association with one or more traits (P
      < 0.05). CONCLUSION: Genetic variation in NPY1R, NPY2R, NPY5R, CPE, IL15, and
      SFRP2, detected using linkage analysis in hypertensive siblings, was associated
      with left ventricular phenotypes in blacks and/or whites.

PMID- 19593216
TI  - Successful ambulation by surgical conversion in a complex form of epigastric
      heteropagus.
AB  - A female neonate with a complex form of epigastric heteropagus and with three
      legs was referred to us. The left leg appeared normal, the central one was
      hypoplastic and resected 1 month after birth, and the right one projected in the
      cranial direction with knee flexion contracture. Three bones of the parasite were
      sandwiched between the right ilium and the ischiopubic bones of the autosite. At
      the age of 4, we performed the subtrochanteric femoral osteotomy with 90 degrees
      of varization and rotation, along with knee disarticulation. Ambulation was
      successfully achieved with the prosthesis with a multiaxis knee unit.

PMID- 19593217
TI  - Intraosseous pseudotumour of the talus in a child with severe haemophilia.
AB  - We report a case of a large pseudotumour in the right talus of an 11-year-old boy
      with severe haemophilia A. The described intraosseous lesion was treated with
      surgical curettage and autologous bone grafting. Twenty months postoperatively
      computed tomography scan showed no signs of recurrence. Forty months
      postoperatively radiological studies confirmed satisfactory incorporation of the
      graft, no evidence of bone growth disturbance and improvement of Pettersson score
      of the ankle joint. At the same time, regarding his clinical situation, he was
      able to fully participate in his daily activities, presenting painless and almost
      full range of motion of his right ankle joint. Surgical intervention seems to be
      the best option in treating a big pseudotumour of the talus during childhood. As
      conservative management in the treatment of large lesions may fail, disastrous
      complications like a pathological fracture may happen. Anatomical reconstruction
      of a talus when pseudotumour and pathological fracture coexist is a major
      challenge for an orthopaedic surgeon.

PMID- 19593218
TI  - Permanent brachial plexus birth palsy does not impair the development and
      function of the spine and lower limbs.
AB  - Permanent brachial plexus birth palsy (BPBP) impairs the function of the affected
      upper limb. Avulsion type root injuries may damage the cervical spinal cord.
      Whether abnormal function of an upper limb affected by BPBP has any observable
      effects on the development of the locomotion system and overall motor function
      has not been clarified in depth. A total of 111 patients who had undergone
      brachial plexus surgery for BPBP in infancy were examined after a mean follow-up
      time of 13 (5-32) years. Patients' physical activities were recorded by a
      questionnaire. No significant inequalities in leg length were found and the
      incidence of structural scoliosis (1.7%) did not differ from that of the
      reference population. Nearly half of the patients (43%) had asynchronous motion
      of the upper limbs during gait, which was associated with impaired upper limb
      function. Data obtained from the completed questionnaires indicated that only few
      patients were unable to participate in normal activities such as: bicycling,
      cross-country skiing or swimming. Not surprisingly, 71% of the patients reported
      problems related to the affected upper limb, such as muscle weakness and/or joint
      stiffness during the aforementioned activities.

PMID- 19593219
TI  - Effect of potentiating exercise volume on vertical jump parameters in
      recreationally trained men.
AB  - High-force activities have demonstrated postactivation potentiation (PAP) and may
      enhance performance in athletes; however, the efficacy of high-force activities
      to generate PAP in recreationally trained men remains unclear. The purpose of
      this study was to investigate the effect of high-force back squat volume on
      vertical jump (VJ) height, ground reaction force (GRF), impulse (IMP), and
      takeoff velocity (TOV) in recreationally trained men. Sixteen recreationally
      trained men (age 24.56 +/- 2.10 years, height 174.53 +/- 8.54 cm, mass 84.59 +/-
      14.75 kg, and 1 repetition maximum [1RM] back squat 124.71 +/- 17.58 kg) with at
      least 1 year of back squat experience completed 5 testing sessions separated by a
      minimum of 72 hours' rest. On session 1, subjects completed VJ testing without a
      potentiating exercise intervention (control condition) in a test-retest fashion
      (3 VJs, 5 minutes seated rest, and 3 more VJs) and performed 1RM back squat
      testing. Subjects completed the subsequent 4 testing sessions in a test-retest
      fashion (3 VJs, experimental condition, 5 minutes seated rest, and 3 more VJs) in
      random order. The 4 experimental conditions required subjects to perform the back
      squat using a load of 85% 1RM with volumes of 1 x 2, 1 x 3, 1 x 4, or 1 x 5.
      Analysis of variance revealed no significant (p > 0.05) condition by time
      interactions for any dependent variable; however, there were significant (p <
      0.05) main effects for time for GRF (pre 2,123.74 +/- 422.86 N, > post 2,094.53
      +/- 390.99 N) and IMP (pre 210.88 +/- 100.97 Nxs, > post 204.63 +/- 106.14 Nxs)
      but not for VJ or TOV. These results suggest that 85% 1RM back squat volume
      assignments do not produce a VJ potentiation response in recreationally trained
      men.

PMID- 19593220
TI  - Effect of warm-up with different weighted bats on normal baseball bat velocity.
AB  - Traditionally, baseball players have used a heavy bat for warm-up before
      competition. Because bat velocity is an essential component to hitting a
      baseball, and because players warm up differently, there is a need to investigate
      the best way to maximize post warm-up bat velocity. The purpose of this study was
      to determine the effects of warm-up with different weighted bats on normal
      baseball bat velocity. Nineteen recreational male baseball players (age, 24.5 +/-
      3.9 years; height, 181.1 +/- 8.4 cm; body mass, 87.9 +/- 18.4 kg) participated in
      this study. Three different randomized warm-up conditions were completed and
      analyzed for velocity and for their effect on post warm-up normal baseball bat
      velocity. Subjects were instructed to perform 5 maximal swings with each of 3
      different weighted bats-light (LB = 9.6 oz), normal (NB = 31.5 oz), and heavy (HB
      = 55.2 oz)-followed by 30-second rest and then 5 swings of the NB. Analysis of
      variance revealed that warm-up velocity of the LB (63.57 +/- 3.58 mph) was
      significantly (p < 0.05) faster than that of NB (51.25 +/- 3.01 mph) and HB
      (41.79 +/- 3.01 mph), whereas warm-up velocity of NB was also significantly
      faster than that of HB. For post warm-up, LB (52.29 +/- 2.68 mph) and NB (50.60
      +/- 3.04 mph) produced significantly faster velocity of the normal bat than the
      HB (48.26 +/- 2.98 mph). Warming up with 5 swings of a light or normal bat
      appears to increase post warm-up velocity of the normal bat when compared with
      warming up with a heavy bat after a rest period of 30 seconds. Within the bat
      weight spectrum of this study, it is suggested that when preparing to hit, 5 warm
      up swings with either a light or normal bat will allow a player to achieve the
      greatest velocity of their normal bat.

PMID- 19593221
TI  - Validation of heart rate monitor-based predictions of oxygen uptake and energy
      expenditure.
AB  - To validate VO2 and energy expenditure predictions by the Suunto heart rate (HR)
      system against a first principle gas analysis system, well-trained male (n = 10,
      age 29.8 +/- 4.3 years, VO2 65.9 +/- 9.7 ml x kg x min) and female (n = 7, 25.6
      +/- 3.6 years, 57.0 +/- 4.2 ml x kg x min) runners completed a 2-stage
      incremental running test to establish submaximal and maximal oxygen uptake
      values. Metabolic cart values were used as the criterion measure of VO2 and
      energy expenditure (kJ) and compared with the predicted values from the Suunto
      software. The 3 levels of software analysis for the Suunto system were basic
      personal information (BI), BI + measured maximal HR (BIhr), and BIhr + measured
      VO2 (BIhr + v). Comparisons were analyzed using linear regression to determine
      the standard error of the estimate (SEE). Eight subjects repeated the trial
      within 7 days to determine reliability (typical error [TE]). The SEEs for oxygen
      consumption via BI, BIhr, and BIhr + v were 2.6, 2.8, and 2.6 ml.kg.min,
      respectively, with corresponding percent coefficient of variation (%CV) of 6.0,
      6.5, and 6.0. The bias compared with the criterion VO2 decreased from -6.3 for
      BI, -2.5 for BIhr, to -0.9% for BIhr + v. The SEE of energy expenditure improved
      from BI (6.74 kJ) to BIhr (6.56) and BIhr + v (6.14) with corresponding %CV of
      13.6, 12.2, and 12.7. The TE values for VO2 were approximately 0.60 ml x kg x min
      and approximately 2 kJ for energy expenditure. The %CV for VO2 and energy
      expenditure was approximately 1 to 4%. Although reliable, basic HR-based
      estimations of VO2 and energy expenditure from the Suunto system underestimated
      VO2 and energy expenditure by approximately 6 and 13%, respectively. However,
      estimation can be improved when maximal HR and VO2 values are added to the
      software analysis.

PMID- 19593222
TI  - Reliability of the Ekblom soccer-specific endurance test.
AB  - The aim of this study was to explore and quantify measurement reliability of the
      Ekblom endurance test. Experienced university soccer players (n = 19; age = 20.5
      +/- 2.5 years; mass = 80.4 +/- 9.8 kg; and stature = 179.0 +/- 6.0 cm) completed
      the Ekblom endurance test on 3 separate occasions. Time to complete trial 1 (549
      +/- 26 seconds) and trial 2 (547 +/- 26 seconds) was analyzed, and despite no
      significant difference (F1,18 = 4.119, p = 0.057, etaP = 0.186) between trials,
      some evidence of systematic bias was observed in the data. Therefore, trial 2
      data were compared with those of trial 3 (548 +/- 27 seconds), with trial 1 data
      removed. The subsequent analysis (F1,18 = 0.740, p = 0.401, etaP = 0.039) showed
      a reduction in the risk of making a type II error when compared with the previous
      analysis. From the reliability analyses (3,1 intraclass correlation = 0.983, SEM
      = +/-3 seconds, smallest worthwhile change = 5 seconds, standard error of
      prediction [95% confidence intervals] = +/- 9 seconds), a high level of
      measurement reliability was observed and the sensitivity of the test to monitor
      changes was "good." In summary, it was shown that a test that involves a variety
      of soccer-specific forms of locomotion can be highly reliable and sensitive to
      detect change. In light of the systematic bias found, we do, however, recommend a
      familiarization session to be scheduled before the introduction of this test.

PMID- 19593223
TI  - Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and
      clinicoradiologic presentation.
AB  - Retroperitoneal fibrosis (RPF) is a rare disorder of unknown etiology. Its
      incidence is unknown, and the insidious and nonspecific nature of symptoms may
      contribute to considerable diagnostic delay. We conducted the current study to
      assess the incidence and clinicoradiologic characteristics of idiopathic RPF. For
      this, we evaluated prospectively 53 consecutive patients with a diagnosis of
      idiopathic RPF at our tertiary care referral center from April 1998 through
      January 2008.Calculated annual incidence of RPF was 1.3/100,000 inhabitants. Mean
      age was 64 +/- 11.1 (SD) yr; male-female ratio was 3.3:1.0. Median duration of
      symptoms was 6.0 mo (IQR 3.0-12.0). Abdominal, flank, and/or back pain and
      discomfort were the major symptoms, with visual analogue scale scores of 49 +/-
      27.2 mm and 43 +/- 29.4 mm for pain and discomfort, respectively. Female patients
      had higher erythrocyte sedimentation rate (ESR), higher white blood cell count,
      and lower hemoglobin content than male patients at presentation. Computed
      tomography-documented maximal mass thickness amounted to 35 +/- 16.6 mm;
      craniocaudal length amounted to 137 +/- 48.8 mm. RPF mass extension up to or
      above the level of the renal vessels was noted in 3 patients (6%). Six patients
      (11%) presented with atypical RPF localization and/or bulky mass. Localized
      lymphadenopathy adjacent to the RPF mass was observed frequently (25%). Patients
      with hydronephrosis (56%) presented earlier than patients without hydronephrosis,
      with higher creatinine and greater mass thickness but similar pain severity.
      Patients were typically at high cardiovascular risk with increased-often
      aneurysmal-infrarenal aortic diameter (25.0 mm, IQR 22.0-30.0). RPF mass
      distribution was similar in patients with or without aneurysmal dilation.
      Occupational asbestos exposure (20%) and asbestos-related pleural changes (17%)
      were frequent among males. Previous or concurrent chronic inflammatory disease
      and/or autoimmune disease was noted in 8 patients (15%). Multivariate analysis
      revealed an independent association of ESR values with severity of pain and
      discomfort. Smoking was independently associated with infrarenal aortic
      diameter.In summary, annual RPF incidence is higher than previously assumed. Age
      at diagnosis and male-female ratio seem to have changed over time. RPF typically
      affects patients at high cardiovascular risk, including increased aortic
      diameter. Clinical presentation is influenced by sex, severity of inflammation
      and presence of hydronephrosis. Prolonged asbestos exposure and asbestos-related
      pleural changes were frequent among males. Localized lymphadenopathy adjacent to
      the RPF mass occurs frequently and should not confuse RPF diagnosis.

PMID- 19593224
TI  - Retroperitoneal fibrosis: the clinical, laboratory, and radiographic
      presentation.
AB  - Retroperitoneal fibrosis (RPF) is an inflammatory disorder that affects the
      infrarenal great vessels and surrounding structures. Although first described in
      1948 by Ormond, much of the information currently available on this disease is
      conflicting and results from multiple definitions used by different
      investigators. We conducted the current study to describe the clinical,
      laboratory, and radiographic presentation of RPF from a single center using data
      collected in a prospective fashion.Data on all patients who were referred to our
      RPF clinic were prospectively collected. We obtained information on presenting
      signs and symptoms, and on the presence or absence of "traditional risk factors,"
      comorbidities, and family histories. All patients underwent the same battery of
      laboratory testing, including complete blood count, renal function profile,
      erythrocyte sedimentation rate (ESR), thyroid-stimulating hormone, and
      antinuclear antibodies (ANA). All patients had contrast-enhanced computed
      tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis.
      The extent of disease was classified based on the anatomic location of the soft
      tissue density.Forty-eight patients (26 male and 22 female) met the criteria for
      RPF and were included in the study. The mean age was 54.25 years. Few patients
      had traditional risk factors for RPF. Pain and weight loss were the most common
      presenting symptoms. The mean hemoglobin was 11.6 g/dL. The mean ESR was 40.5
      mm/h. Nine patients had positive ANA, all with negative antibodies to dsDNA. CT
      or MRI revealed the presence of a periaortic soft-tissue density in all (100%)
      patients; 69% had pericaval involvement, 62% had obstruction of 1 or both
      ureters, and 35% of patients had involvement of the renal artery or renal vein.In
      the current report we present the demographics and laboratory and radiographic
      presentation of a homogenous group of patients with RPF. We attempt to solidify a
      proper scheme of classification for the disease, and suggest an anatomic
      classification system that may be used for future studies.

PMID- 19593225
TI  - Retroperitoneal fibrosis: new insights into clinical presentation and diagnosis.

PMID- 19593226
TI  - Tigecycline use in cancer patients with serious infections: a report on 110 cases
      from a single institution.
AB  - Tigecycline, the first in a new class of glycylcyclines, has been approved for
      the treatment of complicated skin and skin structure and intraabdominal
      infections in adults. However, clinical data on its safety and effectiveness in
      cancer patients are lacking. We reviewed the records of all cancer patients
      treated with tigecycline for more than 48 hours between June 2005 and September
      2006 at our institution and identified 110 consecutive cases (median age, 58 yr;
      range, 18-81 yr). We collected data on demographics, cancer type, tigecycline
      indication, microbiologic characteristics, side effects, and outcome. Sixty-four
      (58%) patients had hematologic malignancies; 27 patients had undergone
      hematopoietic stem cell transplantation. Thirty-one (28%) patients had
      neutropenia, and 62 (56%) were in the intensive care unit at the start of
      therapy. Most patients (106 [96%]) received tigecycline as a second-line agent
      (after not responding to other broad-spectrum antibiotics), and 101 (92%)
      received it in combination with an antipseudomonal drug. The mean duration of
      therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received
      tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had
      intraabdominal infections, and 7 (6%) had complicated skin and soft tissue
      infections. Fifty (45%) patients had microbiologically documented infections, and
      the remaining patients had negative cultures at the start of therapy.An overall
      clinical response was noted in 70 (64%) patients. More clinical responses were
      seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p =
      0.029). Patients with microbiologically documented infections had significantly
      higher clinical response rates than patients with non-microbiologically
      documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not
      respond to treatment; 36 of these patients died of active infection during
      tigecycline therapy. Patients with pneumonia had a significantly higher mortality
      rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days
      of follow-up from the date of clinical response, patients with pneumonia had
      significantly shorter survival durations than patients with other infections. Of
      the 42 patients who were not on antiemetics or ventilator support at the start of
      tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced
      nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during
      tigecycline therapy, all of whose stools were negative for Clostridium difficile
      toxin. No serious adverse events related to tigecycline use were identified. The
      combination of tigecycline and an antipseudomonal drug may be appropriate for
      treating refractory infections and multidrug-resistant organisms in cancer
      patients, including hematopoietic stem cell transplant recipients. Patients with
      refractory pneumonia had a relatively low clinical response rate in our study.

PMID- 19593227
TI  - Takayasu arteritis and giant cell arteritis: a spectrum within the same disease?
AB  - Giant cell arteritis (GCA) and Takayasu arteritis (TAK) have been considered
      distinct disorders based on their clinical features, age of onset, and ethnic
      distribution. However, on closer examination, these disorders appear more similar
      than different. The histopathology of arterial lesions in these diseases may be
      indistinguishable. Imaging studies have revealed large vessel inflammation in at
      least 60% of patients with GCA. We questioned whether the distinctions between
      these diseases might in part be an artifact due to bias in gathering historical
      and physical data. We postulated that signs and symptoms of GCA and polymyalgia
      rheumatica occur in patients with TAK but have been under-reported as a result of
      this bias.We performed a retrospective review of 75 patients with TAK and 69
      patients with GCA (per American College of Rheumatology criteria). Signs and
      symptoms attributable to disease within the year before and following diagnosis,
      treatment and interventional outcomes, and mortality were recorded using a
      standardized database. All cases were evaluated by a single physician, using
      identical history and physical examination forms for patients with both
      diseases.Patients were predominantly female (TAK 91%, GCA 82%) and white (TAK
      88%, GCA 95%). New headache was a presenting symptom in 52% of TAK and in 70% of
      GCA patients. All TAK patients underwent vascular imaging studies and were
      demonstrated to have large vessel abnormalities. However, only a subset of
      patients with GCA (43/69, 62%) was similarly studied. Among this group, 73% of
      GCA patients had at least 1 arterial lesion identified. In both TAK and GCA, the
      most common sites of involvement were the aorta (TAK 77%, GCA 65%) and subclavian
      (TAK 65%, GCA 37%) arteries. Compared to patients with TAK, patients with GCA had
      a greater prevalence of jaw claudication (GCA 33%, TAK 5%), blurred vision (GCA
      29%, TAK 8%), diplopia (GCA 9%, TAK 0%), and blindness (GCA 14%, TAK
      0%).Symptoms, signs, and imaging abnormalities that are characteristic of GCA or
      TAK are often present, albeit in differing frequencies, in both disorders. These
      findings lend support to the hypothesis that these diseases may not be distinct
      entities, but represent skewed phenotypes within the spectrum of a single
      disorder. Differences in frequencies of manifestations may reflect a significant
      bias in how data are gathered for patients with each disease, as well as the
      influence of vascular and immunologic senescence.

PMID- 19593228
TI  - Strokes at time of disease diagnosis in a series of 287 patients with biopsy
      proven giant cell arteritis.
AB  - Patients with giant cell arteritis (GCA) generally present with cranial ischemic
      manifestations that are directly related to vascular involvement. They may also
      experience strokes in the territory of the carotid or the vertebrobasilar artery.
      We conducted the current study to assess the frequency and predictors of strokes
      in general, and of vertebrobasilar stroke in particular, at the time of diagnosis
      in a series of 287 consecutive patients with biopsy-proven GCA diagnosed over a
      27-year period at the single hospital for a well-defined population of
      northwestern Spain.During the study period, 8 (2.8%) patients had strokes (1 in
      the carotid and 7 in the vertebrobasilar territory) between the onset of symptoms
      of the disease and 4 weeks after the onset of corticosteroid therapy. Six of the
      7 patients with vertebrobasilar stroke were men. In most cases the
      vertebrobasilar stroke occurred after the onset of corticosteroid therapy.
      Smoking history was more common among patients with vertebrobasilar stroke (p =
      0.01). Patients with vertebrobasilar stroke more commonly had permanent visual
      loss due to arteritic involvement of ophthalmic branches derived from the
      internal carotid (3/7; 42.9%) than the rest of GCA patients (33/280; 11.8%) (p =
      0.05). Patients with strokes had higher hemoglobin values (13.2 +/- 1.5 g/dL)
      than patients without (11.7 +/- 1.6 g/dL) (p = 0.009). Moreover, only 1 (14.3%)
      of the 7 patients with vertebrobasilar stroke had anemia compared to 157 (56.1%)
      of the remaining 280 patients (p = 0.05). The best predictors of stroke were
      permanent visual loss (odds ratio [OR], 5.42) and arterial hypertension (OR,
      5.06). In contrast, women (OR, 0.10) and patients with anemia at the time of
      disease diagnosis (OR, 0.11) had a significantly reduced risk of suffering
      strokes. Smoking history was the best positive predictor of vertebrobasilar
      stroke (OR, 5.22). In contrast, a reduced risk of suffering vertebrobasilar
      strokes was found in individuals who had anemia at the time of GCA diagnosis (OR,
      0.13).Results of the current study show an increased risk of strokes, in the
      vertebrobasilar territory in particular, at the time of GCA diagnosis. Patients
      with biopsy-proven GCA and traditional cardiovascular risk factors or permanent
      visual loss have an increased risk of suffering strokes. Results also suggest a
      potential protective role of anemia against the development of these
      cerebrovascular complications.

PMID- 19593229
TI  - Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis.
AB  - Cardiac disease is a major contributor to disease-related death in Churg-Strauss
      syndrome (CSS). We conducted the current study to determine the prevalence and
      clinical impact of cardiac involvement in CSS patients. We performed a
      multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac
      workup included electrocardiography, echocardiography, cardiac magnetic resonance
      imaging (MRI), and endomyocardial biopsy.We analyzed 49 patients with CSS: 22
      patients had clinical evidence of cardiac involvement. A negative antineutrophil
      cytoplasmic antibodies (ANCA) test and much higher eosinophil counts (9947 vs.
      3657/microL, respectively, p < 0.001) distinguished patients with cardiac
      involvement from those without. Impaired left ventricular function (50%), mild to
      severe valvular insufficiencies (73%), and pericardial effusions (41%) were
      common findings in these patients. Endomyocarditis was found in 13 patients (59%)
      as detected by cardiac MRI, cardiac thrombus formation, and endomyocardial
      biopsy, and was associated with impaired cardiac function. After a mean follow-up
      of 47 months, most patients had regained or maintained good cardiac function.
      However, patients with endomyocarditis had a more severe outcome. Two patients
      died (61 and 99 mo after diagnosis, respectively), both due to severe
      cardiomyopathy and heart failure.Cardiac involvement is common in patients with
      CSS and is associated with the absence of ANCA and high eosinophil counts.
      Endomyocarditis may represent the most severe manifestation eventually causing
      fatal outcome. A structured clinical assessment incorporating cardiac imaging
      with echocardiography and MRI can identify impaired cardiac function and
      endomyocardial abnormalities.

PMID- 19593230
TI  - Halomonas, a newly recognized human pathogen causing infections and contamination
      in a dialysis center: three new species.
AB  - Our Renal Care Center (RCC) is a separate building, performing almost 2500
      outpatient dialysis runs per month. In May 2007, 2 patients developed, days
      apart, bacteremia with an apparently identical nonfermentative Gram-negative rod.
      Because of difficulty identifying the organism, testing in the Biolog system
      identified them as a Halomonas species. Sequencing of approximately 1500 bases of
      the 16S rRNA gene in both organisms in 3 reference laboratories confirmed,
      searching against 3 databases, that the organisms were identical and were
      Halomonas species. There were 54 recognized species of this genus, associated
      with marine or saline sites. Initial attempts at environmental isolation as
      primary cultures, including a 4% salt agar plate, or initial incubation in 6.5%
      salt broth enrichment culture with subculture to agar, to exploit the
      halophilicity of Halomonas, were successful in demonstrating the colonies seen in
      the blood cultures, only from sites not contaminated with other organisms,
      because of competing growth. A more selective method was developed for use on
      samples suspected to be heavily contaminated with other organisms, using the
      strategy of increased salt concentration in a broth enrichment culture to further
      exploit Halomonas halotolerance, and thereby inhibit other organisms. A 16.5%
      salt concentration in brain-heart infusion broth, incubated at 35 degrees C for
      48-72 hours, then subcultured to agar plates incubated in room air at 35 degrees
      C, proved optimal for selection and secondary isolation. With a combination of
      these techniques, 14/15 cultures of dialysates and 10/38 from the outflow
      pathways of the machines were Halomonas positive, compared to 0/31 cultures from
      the inflow side of the machines (including water supplies and storing, mixing,
      and preparation tanks). The exception was sites associated with or downstream of
      bicarbonate influx, 12/54 of which were positive. Two other local hospitals'
      dialysis centers, and our own inpatient dialysis facility, were cultured at sites
      that yielded Halomonas from our RCC, and Halomonas was not isolated. Further
      study by 16S rRNA gene sequencing and DNA-DNA hybridization revealed the cultures
      represented 3 novel species: 1 (H. stevensii sp. nov.) in the patients and
      environment and 2 (H. hamiltonii sp. nov., H. johnsoniae sp. nov.) in the
      environment, most closely related to H. magadiensis. Of 35 speciated isolates, 22
      were H. stevensii, 10 H. johnsoniae, and 3 H. hamiltonii. We hypothesize that the
      RCC became contaminated with these halophilic organisms from bicarbonate used to
      prepare dialysis fluid, and they persist despite cleaning and flushing procedures
      because of biofilm in machines and bicarbonate fluid inflow sites. Our
      experience, together with the review of the literature presented here, indicates
      the genus Halomonas has pathogenic potential.

PMID- 19593231
TI  - Nocardiosis at the turn of the century.
AB  - Nocardia species is an uncommon pathogen that affects both immunosuppressed and
      immunocompetent patients. The clinical and microbiologic spectrum of nocardiosis
      has changed recently due to the widespread use of cotrimoxazole prophylaxis, the
      emergence of new types of immunosuppressed patients, and the improved
      identification of isolates using molecular techniques. Nocardia asteroides was
      traditionally considered the predominant organism, and prophylaxis with
      cotrimoxazole was considered almost universally protective. We conducted the
      current study to determine the incidence of nocardiosis and its microbiologic and
      clinical characteristics in a general hospital over the last 12 years. We
      reviewed the clinical records of all patients in whom Nocardia species was
      isolated from clinical specimens between 1995 and 2006. Nocardia isolates were
      identified by standard procedures and by 5' end 16S rRNA gene polymerase chain
      reaction (PCR) and sequencing. Susceptibility to cotrimoxazole, minocycline,
      imipenem, linezolid, and amikacin was determined by the broth microdilution
      method following the guidelines of the Clinical and Laboratory Standards
      Institute.The incidence of Nocardia infections did not increase significantly
      during the study period (0.39/100,000 inhabitants in 1995-1998 and 0.55/100,000
      inhabitants in 2003-2006). Nocardia was recovered from 43 patients. Six were
      considered to be colonized. The colonizing species were N. farcinica, N. nova,
      and N. asteroides. All colonized patients had severe underlying pulmonary
      conditions and were treated with antimicrobials (6 patients) or corticosteroids
      (4 patients). Invasive nocardiosis was diagnosed in 37 patients (86.5% were men,
      and their mean age was 55.8 +/- 17.3 yr). The most common underlying condition in
      our institution was human immunodeficiency virus (HIV) infection (10 patients;
      27%), followed by chronic obstructive pulmonary disease (8 patients; 21.6%),
      autoimmune diseases (8 patients; 21.6%), solid organ transplantation (7 patients;
      18.9%), and cancer (4 patients; 10.8%). The most important risk factor for
      nocardiosis was corticosteroid administration (23 patients; 62.2%). Nocardiosis
      affected the lungs in 26 cases (70.3%), the skin in 3 cases (8.1%), and the
      central nervous system in 2 cases (5.4%). It was disseminated in 5 cases (13.5%)
      and caused otomastoiditis in 1 (2.7%). The species identified were N.
      cyriacigeorgica (32.4%), N. farcinica (24.3%), N. otitidiscaviarum (10.8%), N.
      veterana (8.1%), N. nova (5.4%), N. abscessus (5.4%), N. asiatica (2.7%), N.
      beijingensis (2.7%), N. brasiliensis (2.7%), N. carnea (2.7%), and Nocardia
      species (2.7%).Linezolid and amikacin were uniformly active against all the
      isolates, whereas 29.7% of isolates showed intermediate susceptibility to
      minocycline (minimum inhibitory concentration = 2 mg/L), 10.8% were resistant to
      cotrimoxazole, and 5.4% were resistant to imipenem. Nocardiosis occurred while
      the patients were on cotrimoxazole prophylaxis in 8 cases (21.6%). The strains
      isolated from these patients were susceptible to cotrimoxazole in 5 cases (62.5%)
      and resistant in 3 (37.5%). Overall, 13 patients died (35.1%); related mortality
      was 21.6% (8 patients). We conclude that HIV infection has become the most common
      underlying condition for invasive nocardiosis in our institution, followed by
      chronic lung disease. Previous use of corticosteroids was the main risk factor
      and was present in more than half the patients. New species of Nocardia have been
      identified, and administration of cotrimoxazole prophylaxis should no longer be
      considered highly reliable protection against nocardiosis. Larger studies of
      nocardiosis are required to better identify risk factors associated with
      mortality, and alternative and more effective methods of prevention must be
      developed.

PMID- 19593232
TI  - Does use of estrogens decrease the Breslow thickness of melanoma of the skin?
      Oral contraceptives and hormonal replacement therapy.
AB  - Recently, we showed there was a cumulative dose-dependent association between the
      use of estrogens and the incidence of cutaneous melanoma (CM). This association
      was shown for both oral contraceptives (OC) and hormonal replacement therapy
      (HRT). Some in-vitro studies, however, have suggested a direct inhibitory effect
      on melanoma tumor growth. Therefore, the use of different types of estrogens, OC
      and HRT, may be associated with a decreased Breslow thickness. Consequently, the
      clinical impact of our earlier findings may be limited. In this study, we
      investigated whether estrogen use (0.5 year), OC or HRT, is associated with a
      decreased Breslow thickness. For this study, we linked the national Dutch
      pathology database (PALGA) to a pharmacy database (PHARMO). Cases were women with
      a primary CM between 1 January 1991 and 14 December 2004, aged > or =18 years and
      having > or =3 years of follow-up before diagnosis of CM. In total, 687 women
      with melanoma were included. Univariable linear regression analysis suggested a
      decreased Breslow thickness with the use of OC and HRT. Statistically significant
      interaction was observed between age and estrogen use (P<0.01) suggesting effect
      modification by age. However, in stratified multivariable analyses for different
      age groups (<45, 45-55, > or =55 years), no statistically significant
      associations between the use of OC or HRT and Breslow thickness were observed. In
      conclusion, an association between use of OC and HRT and Breslow thickness could
      not be confirmed.

PMID- 19593233
TI  - Search for hidden secondary causes in postmenopausal women with osteoporosis.
AB  - OBJECTIVE: The prevalence of secondary processes in women with postmenopausal
      osteoporosis (OP) is not well known. The aim of this study was to analyze the
      prevalence of conditions contributing to bone loss in postmenopausal women with
      OP and to evaluate the clinical characteristics and the impact of these disorders
      on the severity of the disease. METHODS: A total of 204 postmenopausal women
      (mean +/- SD age, 64.9 +/- 10 y) with OP were prospectively included. None had an
      evident secondary cause of OP. Bone mineral density assessment, spine x-ray, and
      laboratory tests including parathormone (PTH), 25-hydroxyvitamin D (25OHD),
      thyroid hormones, urinary N-terminal cross-linked telopeptide of type I collagen
      (NTx), and 24-hour urinary calcium and cortisol were performed in all
      participants before treatment. RESULTS: As a group, 82% had low 25OHD levels (<30
      ng/mL), 35% had increased PTH levels (>65 pg/mL), and 20% had hypercalciuria
      (>250 mg/24 h). In addition, 41% had increased NTx urinary levels (>65
      nmol/mmol). PTH levels were related to age and were higher in women with femoral
      Z score less than -2.0 (80.3 pg/mL vs 57.7 pg/mL; P = 0.03). Participants with
      increased urinary NTx showed lower lumbar T and Z scores, whereas women with low
      25OHD levels had lower femoral neck bone mineral density and T score values. In
      addition, participants with vertebral fractures had higher prevalence of 25OHD
      levels less than 20 ng/mL (69.2% vs 53.4%; P < 0.05). CONCLUSIONS: Secondary
      processes that contribute to low bone mass in postmenopausal women with OP are
      frequent, especially vitamin D insufficiency, increased PTH values, and
      hypercalciuria. In addition, increased bone resorption is frequently observed in
      this group of women. Most of these processes contributed to the severity of the
      disease.

PMID- 19593235
TI  - Biodistribution study and identification of inflammatory sites using nanocapsules
      labeled with (99m)Tc-HMPAO.
AB  - PURPOSE: To evaluate the ability of polymeric nanocapsules (NCs) radiolabeled
      with technetium-99m D,L-hexamethylpropyleneamine oxime (Tc-HMPAO) to identify
      inflammatory process in an experimental model. METHODS: NCs were prepared by
      interfacial deposition of preformed biodegradable polymer [poly (D,L-lactic acid)
      (PLA) and PLA-PEG (polyethyleneglycol)] followed by a solvent displacement. The
      size and homogeneity, and zeta potential of the NC preparations were determined
      in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry,
      respectively. The NCs radiolabeled with Tc-HMPAO were administered intravenously
      to Wistar male rats bearing a focal inflammation induced by subplantar injection
      of carrageenan in the right foot. At preestablished time intervals, the animals
      were anesthetized, tissues were removed and radioactivity was determined using an
      automatic scintillation apparatus. RESULTS: The average diameter calculated by
      photon correlation spectroscopy varied from 216 to 323 nm. The biodistribution
      studies showed a greater uptake of the PEG surface-modified Tc-HMPAO-NC by the
      inflamed paws when compared with the respective controls. There was no
      significant difference in the uptake of conventional Tc-HMPAO-NC and of free Tc
      HMPAO by inflamed and control paws. These results indicate that the PLA-PEG Tc-NC
      showed a higher uptake in inflammation compared with free complex and may be
      useful as a radiotracer to identify these foci.

PMID- 19593238
TI  - To the editor: treatment of convergence insufficiency in childhood: a current
      perspective.

PMID- 19593234
TI  - Association analyses suggest multiple interaction effects of the
      methylenetetrahydrofolate reductase polymorphisms on timing of menarche and
      natural menopause in white women.
AB  - OBJECTIVE: This study aimed to investigate whether polymorphisms of the
      methylenetetrahydrofolate reductase (MTHFR) gene are associated with age at
      menarche and age at natural menopause in white women. METHODS: In a cross
      sectional study, a total of 305 randomly selected unrelated white women were
      genotyped for six single nucleotide polymorphisms (SNPs) of the MTHFR gene
      (including one common replacement, rs1801133). This sample was comprehensively
      analyzed for the association of the SNPs with age at menarche. Then a subsample
      of 210 women who experienced natural menopause was analyzed for the association
      of the MTHFR gene with age at natural menopause. RESULTS: Duration of breast
      feeding was a significant predictor of earlier natural menopause (P < 0.05). No
      individual SNPs were associated with either age at menarche or age at natural
      menopause. However, three significant (P < 0.05) SNP-SNP interaction effects
      (rs2066470/rs1476413, rs2066470/rs4846049, and rs17037390/rs4846049) on the onset
      of menarche were determined. Three haplotypes were significantly associated with
      age at menopause (P < 0.05). Four SNPs (rs2066470, rs17037390, rs1801133, and
      rs4846048) indicated significant interaction effects with various lifestyle
      factors on age at natural menopause. CONCLUSIONS: The results of our study
      suggest that the MTHFR gene may influence the onset of menarche and natural
      menopause. This effect is probably due to the multiple SNP-SNP and SNP
      environment interactions. More independent studies are needed to further clarify
      the possible contribution of this gene to the timing of menarche and menopause.

PMID- 19593236
TI  - Times are changing in an exciting way.

PMID- 19593239
TI  - Nearpoint phorias after nearwork predict ADHD symptoms in college students.
AB  - PURPOSE: Phorometric findings have been observed to change with stress. We test
      the hypothesis that postnearwork phorias predict symptoms that have been
      theorized to result from nearwork-induced visual stress. METHODS: We measured
      nearpoint and farpoint dissociated phorias in 37 unselected college students with
      an alternate cover test both before and after a challenging reading comprehension
      test. We also assessed a broad range of putative attention deficit hyperactivity
      disorder (ADHD)-related symptoms with the Nadeau College-level ADHD
      Questionnaire. RESULTS: For phorias measured at nearpoint after nearwork, greater
      deviation from the median phoria (three exophoria) predicted higher symptoms (rho
      (35) = 0.52, p < 0.001), whether that deviation was in a convergent or a
      divergent direction (both rho's (18) = >0.48, p's < 0.04). An analogous result
      was obtained for "distance-near" stimulus accommodative convergence to
      accommodation (AC/A) ratios calculated from phorias, where greater deviation from
      median postnearwork AC/A ratio predicted higher symptoms (rho (35) = 0.52, p <
      0.0001). Symptoms did not correlate with prenearwork phorias, prenearwork AC/A
      ratios, or postnearwork farpoint phorias (p's > 0.05). CONCLUSIONS: Phorias
      postnearwork, but not prenearwork, predicted self-reported ADHD-related symptoms
      in college students. These results link binocular imbalance immediately after
      sustained nearwork to symptoms theorized to result from nearwork-induced visual
      stress.

PMID- 19593241
TI  - Neurally adjusted ventilatory assist in children: an observational study.
AB  - OBJECTIVES: To assess patient safety and to evaluate operator acceptance to the
      technology of neurally adjusted ventilatory assist. DESIGN: A within-patient
      crossover study. SETTING: A ten-bed tertiary care university hospital pediatric
      intensive care unit. PATIENTS: A total of 21 mechanically ventilated infants and
      children aged 2 days to 15 yrs suffering from a variety of disorders. The
      majority of patients were treated after cardiac surgery. INTERVENTIONS: In
      patients with pressure-support ventilation, a nasogastric neurally adjusted
      ventilatory assist catheter was positioned to detect the diaphragm electrical
      impulse. Initiation and termination of ventilatory support for each breath could
      then be regulated either through conventional volume or pressure changes or
      through changes in the detected diaphragm electrical impulse signal. Ventilation
      was started as pressure-support ventilation for 30 mins, changed to neurally
      adjusted ventilatory assist for 30 mins, switched back to pressure-support
      ventilation for 30 mins and then neurally adjusted ventilatory assist until an
      end-point criterion was reached. MEASUREMENTS AND MAIN RESULTS: There were no
      serious adverse events during the study and all patients were circulatory and
      respiratory stable. The neurally adjusted ventilatory assist catheter was easy to
      place. The treatment time with neurally adjusted ventilatory assist ranged from 1
      to 8 hrs (median = 2.5 hrs). During neurally adjusted ventilatory assist, the
      peak airway pressures decreased as compared with pressure-support mode but the
      mean airway pressures were not significantly changed.The respiratory rates
      increased during neurally adjusted ventilatory assist. The neural trigger on was
      first in 68% (median) whereas the neural trigger off was first in 88% (median) as
      compared with the pneumatic trigger on and off. Eight of the patients could be
      extubated in close connection to the termination of the neurally adjusted
      ventilatory assist treatment. CONCLUSIONS: We feel that neurally adjusted
      ventilatory assist would be safe and potentially efficacious to ventilate infants
      and children. It has the potential for improved patient-ventilator synchrony,
      decreasing airway pressures, and it might lead to earlier extubation.

PMID- 19593240
TI  - Development of a battery of functional tests for low vision.
AB  - PURPOSE: We describe the development and evaluation of a battery of tests of
      functional visual performance of everyday tasks intended to be suitable for
      assessment of low vision patients. METHODS: The functional test battery comprises
      Reading rate: reading aloud 20 unrelated words for each of four print sizes (8,
      4, 2, & 1 M); Telephone book: finding a name and reading the telephone number;
      Medicine bottle label: reading the name and dosing; Utility bill: reading the due
      date and amount due; Cooking instructions: reading cooking time on a food
      package; Coin sorting: making a specified amount from coins placed on a table;
      Playing card recognition: identifying denomination and suit; and Face
      recognition: identifying expressions of printed, life-size faces at 1 and 3 m.
      All tests were timed except face and playing card recognition. Fourteen normally
      sighted and 24 low vision subjects were assessed with the functional test
      battery. Visual acuity, contrast sensitivity, and quality of life (National Eye
      Institute Visual Function Questionnaire 25 [NEI-VFQ 25]) were measured and the
      functional tests repeated. Subsequently, 23 low vision patients participated in a
      pilot randomized clinical trial with half receiving low vision rehabilitation and
      half a delayed intervention. The functional tests were administered at enrollment
      and 3 months later. RESULTS: Normally sighted subjects could perform all tasks
      but the proportion of trials performed correctly by the low vision subjects
      ranged from 35% for face recognition at 3 m, to 95% for the playing card
      identification. On average, low vision subjects performed three times slower than
      the normally sighted subjects. Timed tasks with a visual search component showed
      poorer repeatability. In the pilot clinical trial, low vision rehabilitation
      produced the greatest improvement for the medicine bottle and cooking instruction
      tasks. CONCLUSIONS: Performance of patients on these functional tests has been
      assessed. Some appear responsive to low vision rehabilitation.

PMID- 19593242
TI  - Cardiac output measurement using an ultrasound dilution method: a validation
      study in ventilated piglets.
AB  - OBJECTIVE: To assess agreement between a new method of cardiac output monitoring,
      using ultrasound dilution technology and ultrasound transit time-based
      measurement of pulmonary blood flow in a piglet model. DESIGN: Prospective,
      experimental juvenile animal study. SETTING: Animal laboratory of a university
      hospital. SUBJECTS: Nine random-bred piglets. INTERVENTIONS: After the animals
      received general anesthesia, we placed intravascular arterial and central venous
      catheters with the tip positioned in the abdominal aorta and the right atrium,
      respectively. The catheters were connected to the ultrasound dilution cardiac
      output monitor. An ultrasound transit time perivascular flow probe was positioned
      around the common pulmonary artery and served as the standard reference
      measurement. Cardiac output was manipulated during the experiment by creating
      hemorrhagic hypotension. Ultrasound dilution cardiac output was measured
      intermittently with injection volumes of 0.5 mL/kg and 1.0 mL/kg of isotonic
      saline at body temperature. MEASUREMENTS AND MAIN RESULTS: Ultrasound dilution
      cardiac output (Q) measurement was compared with pulmonary blood flow (Q). Bias,
      defined as Q minus Q, was calculated for each measurement. Mean bias with
      standard deviation was calculated for measurements with volumes of injected
      saline, 0.5 mL/kg and 1.0 mL/kg, and compared using the Mann-Whitney U test. Mean
      bias (sd) between Q and Q was 0.040 (0.132) and 0.058 (0.136) L/min for
      measurement with 0.5 mL/kg and 1.0 mL/kg of isotonic saline, respectively (no
      statistically significant difference). CONCLUSIONS: Ultrasound dilution cardiac
      output measurement is reliable in piglets with the use of a small volume of a
      nontoxic indicator (isotonic saline).

PMID- 19593243
TI  - Extracorporeal membrane oxygenation and term neonatal respiratory failure deaths
      in the United Kingdom compared with the United States: 1999 to 2005.
AB  - OBJECTIVE: To compare national neonatal extracorporeal membrane oxygenation data
      and deaths from primary respiratory disorders of term neonates between the United
      Kingdom and the United States from 1999 to 2005. DESIGN: Cross-sectional study.
      SETTING: National data sets from the United Kingdom and the United States.
      PATIENTS: Neonatal extracorporeal membrane oxygenation patients submitted to the
      Extracorporeal Life Support Organization Registry and national birth and death
      registrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Meconium
      aspiration syndrome was the most common indication for extracorporeal membrane
      oxygenation in the United Kingdom: 50.6% vs. 25.8% in the United States (p <
      .001). Congenital diaphragmatic hernia was most common indication for
      extracorporeal membrane oxygenation in the United States: 30.7% vs. 15.4% in the
      United Kingdom (p < .001).Extracorporeal membrane oxygenation use was greater in
      the United States than the United Kingdom: rate ratio, 1.81 (95%, confidence
      interval, 1.64, 2.00). The extracorporeal membrane oxygenation rate decreased
      over time in the United States (p < .001) but was unchanged for all diagnoses in
      the United Kingdom (p = .49). The rates of extracorporeal membrane oxygenation
      use for meconium aspiration syndrome were equivalent in both countries: rate
      ratio, 0.92 (95% confidence interval, 0.80, 1.07) but greater in the United
      States for congenital diaphragmatic hernia: rate ratio, 3.60, (95% confidence
      interval, 2.82, 4.66) and persistent pulmonary hypertension newborn: rate ratio,
      4.67 (95% confidence interval, 3.33, 6.74).National neonatal death rates included
      nonextracorporeal membrane oxygenation + extracorporeal membrane oxygenation
      death. Meconium aspiration syndrome deaths were equivalent overall between the
      two countries: rate ratio, 0.99 (95% confidence interval, 0.77, 1.29), but
      decreased in the United States (p < .001) although not in the United Kingdom (p =
      .17). Congenital diaphragmatic hernia deaths were more prevalent in the United
      Kingdom than in the United States: rate ratio, 1.57 (95% confidence interval,
      1.34, 1.84). CONCLUSIONS: Extracorporeal membrane oxygenation is used more often
      in the United States: clinicians seem less willing to offer extracorporeal
      membrane oxygenation for persistent pulmonary hypertension of the newborn and
      congenital diaphragmatic hernia in the United Kingdom. In contrast to the United
      States, no reduction in either extracorporeal membrane oxygenation use or death
      due to meconium aspiration syndrome was observed in the United Kingdom. Early
      transfer to a tertiary center is recommended for term neonates with respiratory
      failure.

PMID- 19593244
TI  - Predictors of bacteremia in infants with diarrhea and systemic inflammatory
      response syndrome attending an urban diarrheal treatment center in a developing
      country.
AB  - OBJECTIVES: To identify clinical and laboratory predictors of bacteremia in
      infants with diarrhea and systemic inflammatory response syndrome and to analyze
      their outcome. STUDY DESIGN: Retrospective, case-control study. SETTING: The
      Special Care Ward of the Dhaka Hospital of the International Centre for Diarrheal
      Disease Research, Bangladesh, Dhaka, Bangladesh. PATIENTS: All the infants (n =
      90) admitted to the Special Care Ward between May 2005 and April 2006 who had a
      blood culture, full peripheral blood count, and serum C-reactive protein
      performed were included in the study. Infant with systemic inflammatory response
      syndrome with confirmed bacteremia (n = 18) constituted cases, and those with
      systemic inflammatory response syndrome but negative blood culture (n = 72)
      constituted the controls. RESULTS: The following features were analyzed by
      comparing the two groups: absent or uncountable peripheral pulses, hypothermia,
      sclerema, altered mental status, white blood cell count, serum C-reactive
      protein, total protein concentrations, and outcome. The case-fatality rate was
      significantly higher among bacteremic infants compared with those without
      bacteremia (33% vs. 6%, p < .01). In the univariate model, sclerema (56% vs. 28%,
      p = .05), hyperglycemia (28% vs. 6%, p < .01), immature neutrophils [3.5 (00,
      6.5) vs. 0.0 (0.0, 3.25); p = .02], higher C-reactive protein [2.7 (1.2, 7.4) vs.
      1.8 (0.5, 4.2); p = .02], and lower serum total protein (51.1 +/- 14.1 vs. 57.6
      +/- 12.2; p = .05) were identified as potential predictors of bacteremia.
      However, in the logistic regression analysis, after adjusting for confounders,
      only hypothermia (odds ratio = 6.4, 95% confidence Interval, 1.6-25.9; p = .01)
      and absent or uncountable peripheral pulse (odds ratio, 12.4, 95% confidence
      interval, 1.9-83.4; p < .01) remained significant independent predictors of
      bacteremia. CONCLUSIONS: Our data suggest that, in infants presenting with
      diarrhea and systemic inflammatory response syndrome, coexistence of hypothermia
      and absent or uncountable peripheral pulse is strongly associated with
      bacteremia. Bacteremia in this patient group is associated with high case
      fatality rates.

PMID- 19593246
TI  - A prospective crossover comparison of neurally adjusted ventilatory assist and
      pressure-support ventilation in a pediatric and neonatal intensive care unit
      population.
AB  - OBJECTIVE: To compare neurally adjusted ventilatory assist ventilation with
      pressure-support ventilation. DESIGN: Prospective, crossover comparison study.
      SETTING: Tertiary care pediatric and neonatal intensive care unit. PATIENTS:
      Sixteen ventilated infants and children: mean age = 9.7 months (range = 2 days-4
      yrs) and mean weight = 6.2 kg (range = 2.4-13.7kg). INTERVENTIONS: A modified
      nasogastric tube was inserted and correct positioning was confirmed. Patients
      were ventilated in pressure-support mode with a pneumatic trigger for a 30-min
      period and then in neurally adjusted ventilatory assist mode for up to 4 hrs.
      MEASUREMENTS AND MAIN RESULTS: Data collected for comparison included activating
      trigger (neural vs. pneumatic), peak and mean airway pressures, expired minute
      and tidal volumes, heart rate, respiratory rate, pulse oximetry, end-tidal CO2
      and arterial blood gases. Synchrony was improved in neurally adjusted ventilatory
      assist mode with 65% (+/-21%) of breaths triggered neurally vs. 35% pneumatically
      (p < .001) and 85% (+/-8%) of breaths cycled-off neurally vs. 15% pneumatically
      (p = .0001). The peak airway pressure in neurally adjusted ventilatory assist
      mode was significantly lower than in pressure-support mode with a 28% decrease in
      pressure after 30 mins (p = .003) and 32% decrease after 3 hrs (p < .001). Mean
      airway pressure was reduced by 11% at 30 mins (p = .13) and 9% at 3 hrs (p = .31)
      in neurally adjusted ventilatory assist mode although this did not reach
      statistical significance. Patient hemodynamics and gas exchange remained stable
      for the study period. No adverse patient events or device effects were noted.
      CONCLUSIONS: In a neonatal and pediatric intensive care unit population,
      ventilation in neurally adjusted ventilatory assist mode was associated with
      improved patient-ventilator synchrony and lower peak airway pressure when
      compared with pressure-support ventilation with a pneumatic trigger. Ventilating
      patients in this new mode seem to be safe and well tolerated.

PMID- 19593245
TI  - Intrahospital transport of children on extracorporeal membrane oxygenation:
      indications, process, interventions, and effectiveness.
AB  - OBJECTIVE: To evaluate indications, process, interventions, and effectiveness of
      patients undergoing intrahospital transport. Critically ill patients supported
      with extracorporeal membrane oxygenation are transported within the hospital to
      the radiology suite, cardiac catheterization suite, operating room, and from one
      intensive care unit to another. No studies to date have systematically evaluated
      intrahospital transport for patients on extracorporeal membrane oxygenation.
      DESIGN: Retrospective cohort analysis. SETTING: Cardiac intensive care unit in a
      tertiary care children's hospital. PATIENTS: All patients on extracorporeal
      membrane oxygenation who required intrahospital transport between January 1996
      and March 2007 were included and analyzed. MEASUREMENTS AND MAIN RESULTS: A total
      of 57 intrahospital transports for cardiac catheterization and head computed
      tomography scans were analyzed. In 14 (70%) of 20 of patients with cardiac
      catheterization, a management change occurred as a result of the diagnostic
      cardiac catheterization. In ten (59%) of 17 patients, bedside echocardiography
      was of limited value in defining the critical problem. In the interventional
      group, the majority of transports were for atrial septostomy. In the head
      computed tomography group, significant pathology was identified, which led to
      management change. No major complications occurred during these intrahospital
      transports. CONCLUSIONS: Although transporting patients on extracorporeal
      membrane oxygenation is labor intensive and requires extensive logistic support,
      it can be carried out safely in experienced hands and it can result in important
      therapeutic and diagnostic yields. To our knowledge, this is the first study
      designed to evaluate safety and efficacy of intrahospital transport for patients
      receiving extracorporeal membrane oxygenation support.

PMID- 19593247
TI  - Dexmedetomidine sedation in children after cardiac surgery.
AB  - OBJECTIVE: To study the efficacy and safety of dexmedetomidine before and after
      early extubation after pediatric cardiac surgery. DESIGN: Prospective,
      observational study. SETTING: University hospital pediatric intensive care.
      PARTICIPANTS: Infants and children undergoing cardiac surgery. INTERVENTIONS: The
      141 patients, depending on the treatment period, were divided between: 1) usual,
      postoperative, continuous, intravenous sedation with chlorpromazine, midazolam,
      or fentanyl (n = 85); and 2) treatment with dexmedetomidine, 0.4 to 0.6
      microg/kg/hr (n = 56). Sedation was titrated to reach a Ramsay score of 4 or 5 by
      administering rescue boluses, as needed. MEASUREMENTS AND MAIN RESULTS: The
      primary and secondary study end points were efficacy of sedation and frequency of
      adverse events, respectively. The numbers of rescue boluses needed and the
      proportion of ineffectively sedated patients were similar in both groups. The
      frequency of bradycardia or hypotension in the dexmedetomidine group was 21.4%
      (8.2% in usual sedative group, p = .04), requiring interventions to restore
      hemodynamic stability in 5.3% of patients (0% in usual sedative group, p = .06).
      Rates of respiratory depression (8.2% vs. 0%, p = .04) and involuntary movements
      (15.3% vs. 3.6%, p = .01) were higher in the usual sedation group. CONCLUSIONS: A
      usual sedation regimen and dexmedetomidine were similarly efficacious. Although
      dexmedetomidine was associated with a lower rate of respiratory depression, it
      caused a higher rate of adverse hemodynamic events, which might be a concern in
      hemodynamically unstable patients.

PMID- 19593249
TI  - Interferon gamma release assays in the evaluation of children with possible
      Mycobacterium tuberculosis infection: a view to caution.

PMID- 19593248
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae in Navajo and White Mountain
      Apache children before the introduction of pneumococcal conjugate vaccine.
AB  - BACKGROUND: Infants and children are frequently colonized with pneumococcus.
      Recent nasopharyngeal acquisition of pneumococcus is thought to precede disease
      episodes. The increased risk of pneumococcal disease among Navajo and White
      Mountain Apache populations has been documented. Little is known about the
      dynamics of pneumococcal carriage in these populations. METHODS: A group
      randomized, controlled trial of 7-valent conjugate pneumococcal vaccine (PnCRM7,
      Wyeth) was conducted on the Navajo and Apache reservations. A nasopharyngeal (NP)
      carriage study was nested in the trial to evaluate the impact of PnCRM7 on
      carriage. Children <6 years of age had NP swabs collected at enrollment and at 6
      and 12 months following enrollment. We analyzed carriage data from children in
      control vaccine randomized communities to describe the epidemiology of
      pneumococcal carriage. RESULTS: Of the 410 participants enrolled, 92% were
      colonized with pneumococcus at least once during the course of the study. Sixty
      three percent of NP specimens were positive for pneumococcus. The most common
      serotypes were 6A, 6B, nontypable, 23F, 14, 19F, 19A, and 9V. Thirty-eight
      percent of isolates were vaccine serotypes. Age <2 years, male sex, daycare
      attendance, and having a sibling colonized with pneumococcus were associated with
      an increased risk of carriage. CONCLUSIONS: The high carriage prevalence among
      Navajo and Apache children reflects an intense exposure to pneumococcus. The lack
      of modifiable risk factors for carriage highlights the importance of preventive
      strategies for disease control.

PMID- 19593250
TI  - Symptomatic and pathophysiologic predictors of hepatitis C virus progression in
      pediatric patients.
AB  - BACKGROUND: The slow progression of hepatitis C virus (HCV) infection could
      ultimately negatively impact pediatric patients during their lifespan. This study
      describes the symptomatic and pathophysiologic presentation of HCV infection in a
      cohort of pediatric outpatients. METHODS: HCV-positive patients were identified
      by diagnosis codes from outpatient visits. Demographic and pathophysiologic
      indicators (comorbidities, reported symptoms, alanine transaminase, aspartate
      transaminase, gamma glutamyl transpeptidase, HCV viral load, genotype, and liver
      biopsy results) were collected and analyzed. RESULTS: We reviewed 62 patients
      with HCV infection who were from 3 months and 19 years of age (M +/- SD, 12.5 +/-
      5.8 years). Sixty percent presented with clinical symptoms of fatigue, joint
      abdominal pain, bruising/bleeding, or other non-specific symptoms. On liver
      biopsy (n = 35) 80% had evidence of inflammation, 57% had fibrosis, and 9% had
      steatosis. All patients with steatosis or cirrhosis reported symptoms. Males were
      significantly more likely than women to be symptomatic (58.3% vs. 41.7%, P =
      0.04). Patients with symptoms were significantly older (M = 13.5 +/- 5.2 vs. 8.9
      +/- 5.5 years, P = 0.003). There was a significant inverse relationship between
      viral load and symptoms (chi = 4.75, P = 0.03). Patients with low viral load (<2
      million copies) were 5 times more likely to have symptoms than those with high
      viral loads (P = 0.03). Significance was also noted between HCV genotype and ALT
      levels (chi = 3.72, P = 0.05). There were no significant relationships between
      symptom status and race, comorbidities, alanine transaminase, aspartate
      transaminase, gamma glutamyl transpeptidase, HCV genotype, or liver histology.
      CONCLUSION: Pediatric patients with HCV can have significant symptoms and
      physiologic liver changes related to HCV.

PMID- 19593251
TI  - Embracing interferon-gamma release assays for diagnosis of latent tuberculosis
      infection.

PMID- 19593253
TI  - Dissemination of Kingella kingae in the community and long-term persistence of
      invasive clones.
AB  - BACKGROUND: Although Kingella kingae is being increasingly recognized as an
      important pediatric pathogen, our current understanding of the transmission of
      the organism is limited. The dissemination of K. kingae in the community was
      studied in 2 ethnic groups living side-by-side in Southern Israel. METHODS:
      Organisms recovered from oropharyngeal cultures, obtained from healthy young
      Jewish and Bedouin children during a 12-month period, were typed by pulsed-field
      gel electrophoresis and compared. RESULTS: Isolates from Bedouin children usually
      differed from those derived from Jews, confirming the relative social isolation
      of the 2 populations and the importance of close mingling in the spread of K.
      kingae. Significant clustering of genotypic clones in households and Bedouin
      neighborhoods was observed, indicating person-to-person transmission through
      intimate contact. Organisms detected in the study were identical to historical
      isolates recovered over the last 15 years from respiratory carriers and patients
      with bacteremia or skeletal infections. CONCLUSIONS: The present study
      demonstrates that children may be asymptomatically colonized in the respiratory
      tract by virulent K. kingae clones. The organism is transmitted from child-to
      child through intimate contact. Some strains exhibit increased fitness and are
      maintained in the population for prolonged periods.

PMID- 19593252
TI  - Fluconazole dosing for the prevention or treatment of invasive candidiasis in
      young infants.
AB  - BACKGROUND: Young infants are susceptible to developmental factors influencing
      the pharmacokinetics of drugs. Fluconazole is increasingly used to prevent and
      treat invasive candidiasis in infants. Dosing guidance remains empiric and
      variable because limited pharmacokinetic data exist. METHODS: Our population
      pharmacokinetic model derived from 357 fluconazole plasma concentrations from 55
      infants (23-40 week gestation) illustrates expected changes in fluconazole
      clearance based upon gestational age, postnatal age, weight, and creatinine. We
      used a Monte Carlo simulation approach based on parametric description of a
      patient population's pharmacokinetic response to fluconazole to predict
      fluconazole exposure (median: 10th and 90th percentile population variability
      range) after 3, 6, and 12 mg/kg dosing. RESULTS: For the treatment of invasive
      candidiasis, a dose of at least 12 mg/kg/d in the first 90 days after birth is
      needed to achieve an area under the concentration curve (AUC) of >400 mg*h/L and
      an AUC/minimum inhibitory concentration (MIC) >50 for Candida species with MIC <8
      microg/mL in > or =90% of <30 week gestation infants and 80% of 30 to 40 week
      gestation infants. The more preterm infants achieve a higher median AUC (682
      mg*hr/L) compared with more mature infants (520 mg*hr/L). For early prevention of
      candidiasis in 23 to 29 week infants, a dose of 3 or 6 mg/kg twice weekly during
      the first 42 days of life is equivalent to an AUC of 50 and 100 mg*hr/L,
      respectively, and maintains fluconazole concentrations > or =2 or 4 microg/mL,
      respectively, for half of the dosing interval. For late prevention, the 6 mg/kg
      dose every 72 hours provides similar exposure to 3 mg/kg daily dose. Infants with
      serum creatinine > or =1.3 mg/dL have delayed drug clearance and dose adjustment
      is indicated if creatinine does not improve within 96 hours. CONCLUSIONS: A
      therapeutic concentration of fluconazole in premature infants with invasive
      candidiasis requires dosing substantially greater than commonly recommended in
      most reference texts. To prevent invasive candidiasis, twice weekly prophylaxis
      regimens can provide adequate exposure when unit specific MICs are taken into
      account.

PMID- 19593254
TI  - An outbreak of varicella in elementary school children with two-dose varicella
      vaccine recipients--Arkansas, 2006.
AB  - BACKGROUND: In June 2006, the Advisory Committee on Immunization Practices (ACIP)
      expanded its June 2005 recommendation for a second dose of varicella vaccine
      during outbreaks to a recommendation for routine school entry second dose
      varicella vaccination. In October 2006, the Arkansas Department of Health was
      notified of a varicella outbreak among students where some received a second dose
      during an outbreak-related vaccination campaign in February 2006. METHODS: The
      outbreak was investigated using a school-wide parental survey with a follow-up
      survey of identified case patients. Vaccination status was verified using state
      and local immunization records. Limited laboratory testing confirmed circulation
      of wild-type varicella, including varicella in 2-dose vaccine recipients.
      RESULTS: Vaccination information was available for 871 (99%) of the 880 children.
      Varicella vaccination coverage was 97% (2-dose, 39%; 1-dose, 58%). A review of
      the February vaccination clinic found no deficiencies; lot numbers did not differ
      between cases and noncases. Varicella was confirmed by PCR in 5 (42%) of 12
      lesion specimens and by IgM in 1 (6%) of 16 serum specimens. Varicella was
      reported in 84 children, including 25 (30%) two-dose and 53 (63%) one-dose
      recipients. Attack rates among 2-dose recipients (10.4%) and 1-dose recipients
      (14.6%) were not significantly different (RR: 0.72, 95% CI: 0.44-1.15). All 2
      dose recipients and 80% of 1-dose recipients reported having 50 or fewer skin
      lesions. CONCLUSION: This outbreak is the first to document varicella in both 1-
      and 2-dose vaccine recipients; both groups had mild disease. The vaccine
      effectiveness of 1 and 2 doses were similar.

PMID- 19593274
TI  - The Patient Health Questionnaire (PHQ-9) scores and the lifestyles of nursing
      students.
AB  - BACKGROUND: The objective of this investigation was to examine depression in, and
      the lifestyles of, 260 college students of a nursing school in nonclinical
      settings. METHODS: The principal measure of depressive symptoms was the 9-item
      depression module from the Patient Health Questionnaire (PHQ-9). Additional
      questions were focused on current stress levels and sleeping, eating, and
      exercising habits. RESULTS: One hundred and fifty-two college students finally
      participated. Overall, the average PHQ-9 score was 7.7 +/- 5.1 (SD). The students
      with PHQ-9 scores of 15 or higher were 9.2%. The average PHQ-9 scores in the 1st
      school year were significantly higher than those of the 4th school year. The
      students feeling stressed had significantly higher PHQ-9 scores than those that
      felt no stress. PHQ-9 scores in the students who had unsatisfactory sleeping
      habits were significantly higher than those in the students who felt they had
      satisfactory sleep. The students who slept less than 5 hours and more than 8
      hours had significantly higher PHQ-9 scores than those who slept 6-7 hours. PHQ-9
      scores in the students who never ate breakfast were higher than those who ate
      breakfast everyday. Moreover, the students who never ate 3 meals daily had higher
      PHQ-9 scores than those who did. CONCLUSIONS: The results suggest that there is a
      strong relationship between the severity of depressive symptoms and the
      lifestyles of college students. This underscores the need to provide effective
      mental health outreach and treatment, including lifestyle modification, at an
      early stage in college life.

PMID- 19593275
TI  - Using the healthcare matrix with interns and medical students as a tool to effect
      change.
AB  - The Healthcare Matrix is a tool developed at Vanderbilt University Medical Center
      which assesses the care of patients using the Accreditation Council for Graduate
      Medical Education (ACGME) competencies and the Institute of Medicine (IOM) Aims
      for Improvement. House staff have been using this tool since 2004 as a means of
      learning the competencies in the daily care of patients. As the residents fill in
      the cells of the Matrix, the opportunities for improvement become evident.
      Anesthesia interns were introduced to the Matrix at bimonthly meetings to analyze
      a real case of complex and/or flawed patient management. Each resident completed
      his/her own Matrix and then the group selected one Matrix as their improvement
      project. This article will present one Matrix case, how quality improvement (QI)
      tools and methods were utilized and what resulting improvements were made. The
      analyzed case revealed numerous flaws with nonstandardized handoffs, incorrect
      and insufficient documentation, and unclear roles/responsibilities. An ideal
      process flowchart was developed highlighting improved handoffs and the need for a
      new admitting policy to the intensive care unit (ICU). The Healthcare Matrix is
      an effective tool for teaching the ACGME competencies in patient care. The
      resequencing of the competencies in the Matrix makes it easy to identify where
      improvements are needed. When taught the tools and methods of quality
      improvement, even interns can make a significant contribution to the improvement
      of patient care.

PMID- 19593276
TI  - Paucisymptomatic retroperitoneal fibrosis unmasked soon after a colonoscopy: a
      prompt resolution.
AB  - A 60-year-old man was diagnosed with retroperitoneal fibrosis. Curiously, his
      back pain became intense immediately after the performance of a colonoscopy. The
      fibrotic mass was seen on computed tomography (CT) of the abdomen. The patient
      developed obstructive nephropathy secondary to bilateral encasing of the ureters.
      Early diagnosis and combined therapy with corticosteroids and ureteral stents led
      to clinical and radiological remission of the disease.

PMID- 19593277
TI  - Pharmaceutical companies' medication assistance programs.

PMID- 19593278
TI  - Sometimes it's not just sinusitis: nasal type natural killer/T-cell lymphoma.

PMID- 19593279
TI  - Perspective on aspartame-induced pseudotumor cerebri.

PMID- 19593280
TI  - Markedly prolonged atrioventricular block with ventricular asystole during sleep.

PMID- 19593281
TI  - Follow your leads: a case of twiddler's syndrome.

PMID- 19593282
TI  - Is pulverized levothyroxine a better therapeutic option in patients with heart
      failure?

PMID- 19593283
TI  - Subphrenic displacement of the colon: from sign to syndrome.

PMID- 19593284
TI  - Chilaiditi syndrome complicated by cecal perforation.
AB  - Chilaiditi sign is a radiological finding which describes the interposition of a
      part of the bowel between the diaphragm and the liver, a finding that can be
      misinterpreted as pneumoperitonium. Chilaiditi syndrome refers to a clinically
      symptomatic patient in the presence of the classical radiographic findings. It is
      a very rare syndrome which usually follows a benign course. Here we report the
      first documented case of Chiliaditi syndrome complicated by cecal perforation.

PMID- 19593285
TI  - A short perspective on the surgical restoration of alaryngeal speech.
AB  - Despite advances in conservative laryngeal surgery and radiotherapy, total
      laryngectomy still remains the procedure of choice for advanced-stage laryngeal
      carcinoma around the world. The loss of natural voice is very often traumatic for
      the total laryngectomy patient, presenting lifelong challenges for communication
      in a world that relies heavily on verbal communication. Functional rehabilitation
      of these patients has long been one of the major challenges facing clinicians,
      but it is only in the last three decades that the emphasis on restoration of
      function and quality of life has become almost as important as cure and survival.
      Although voice restoration for alaryngeal speakers can be attained with any of 3
      speech options - esophageal speech, electrolarynx and surgical voice restoration
      (SVR) using a valve the SVR technique has today become the preferred method and
      'gold standard.' Successful tracheo-esophageal voice restoration in laryngectomy
      patients can be very rewarding, and patients are no longer condemned to silence
      while they await the results of their cancer treatments. They can face the
      challenges of life with the knowledge that a near-normal quality of life is very
      much possible.

PMID- 19593286
TI  - Discharge planning curricula in internal medicine residency programs: a national
      survey.
AB  - BACKGROUND: Transition of patient care from an inpatient to outpatient setting is
      a critical aspect of patient care. The objectives of this study were to describe
      the content and evaluation of the discharge planning curricula (DPC) in internal
      medicine (IM) residency programs and identify program directors' perceptions of
      discharge planning education. METHOD: A 24-item questionnaire was sent to 387 IM
      program directors during April 2005. The analysis was conducted using SPSS
      (version 15). RESULTS: A total of 140 program directors (PDs) responded. Formal
      DPC was offered in 16% (n = 23) of the programs. Hospital resources to coordinate
      transition of care and communication skills were the main curricular content
      areas. Seventy-five percent of the PDs agreed that discharge planning should be
      an important part of the curriculum. More than 50% of the PDs agreed that
      discharge planning would decrease the re-admission rate, and increase patient
      satisfaction and referring physician satisfaction. The programs with a DPC had a
      higher level of agreement that a DPC program would facilitate continuity of care
      between inpatient and outpatient care (P = 0.027) compared to programs without a
      DPC. CONCLUSIONS: The majority of the PDs agreed that DPC should be an important
      curricular component, yet only a few programs offered formal discharge planning
      education. Residency programs need to address this critical aspect of patient
      care within the core curricula.

PMID- 19593287
TI  - The health care matrix formulation: a tool for competency assessment in
      psychiatry residency training.
AB  - OBJECTIVE: To assert the importance of the use of the healthcare matrix
      formulation for competency assessment in psychiatry residency training. METHODS:
      We present a case from our inpatient psychiatric facility and format it in the
      form of the healthcare matrix, which was developed at Vanderbilt University
      incorporating the Institute of Medicine 'aims' and the Accreditation Council for
      Graduate Medical Education 'core competencies'. We also analyze the healthcare
      matrix and elucidate its use in clinical practice. RESULTS: The healthcare matrix
      provides us with a practical tool to analyze any complex episode of patient care,
      like the one in our psychiatric setting, and allows us to learn from the
      shortcomings in order to improve. CONCLUSION: The optimal utilization of this
      tool in the competency assessment of psychiatry residents has an enormous
      practical implication by transforming the case and morbidity and mortality
      conferences into a well-structured learning and improvement format.

PMID- 19593288
TI  - Cardiac tamponade in Still disease: a review of the literature.
AB  - Adult onset Still disease is an unusual multisystem inflammatory disorder of
      unknown etiology and pathogenesis. Among its protean manifestations is
      pericarditis which occurs in approximately 30-40% of patients. Cardiac tamponade
      is a rare complication of pericarditis occurring in the context of Still disease.
      We conducted a review of the English literature pertaining to the occurrence of
      pericardial tamponade in Still disease. We searched relevant journals and the
      PubMed Medline databases. A total of eighteen reported cases were identified; ten
      among children and eight in adults. Treatment of pericardial tamponade was
      medical therapy alone in two cases versus combined modality, medical and surgical
      drainage in the remainder of the cases. Outcomes were death among four of the ten
      children and there was no recurrence of tamponade in the remaining child and
      adult series. This review re-emphasizes the importance of considering Still
      disease in the differential diagnosis of the life-threatening emergency of
      pericardial tamponade.

PMID- 19593289
TI  - Hepatopulmonary syndrome and liver sarcoidosis: a tale of two diseases.
AB  - Hepatopulmonary syndrome (HSP) is characterized by the triad of advanced liver
      disease, arterial hypoxemia, and intrapulmonary vascular dilatation. Most cases
      of HSP are associated with cirrhotic portal hypertension; however, it has also
      been reported in acute liver failure patients. An estimated prevalence of HPS in
      patients with chronic liver disease is around 5-32%. Sarcoidosis is a
      granulomatous disorder with noncaseating granulomas involving the lungs in 90% of
      cases. Sarcoidosis can involve the liver but in only about 1% of cases does it
      lead to cirrhosis and portal hypertension. In this review, we report a rare case
      of liver cirrhosis due to sarcoidosis with associated hepatopulmonary syndrome
      and discuss this in detail.

PMID- 19593290
TI  - Primary dedifferentiated chondrosarcoma of the lung.
AB  - Extraskeletal dedifferentiated chondrosarcomas (DC) are uncommon tumors that
      predominantly occur in the head and neck. Herein, we describe a case of pulmonary
      DC detected in a patient with systemic sclerosis and presenting with a
      symptomatic large pleural effusion and a pulmonary lobar consolidation on chest
      imaging. To the best of our knowledge, this is the first report of pulmonary
      chondrosarcoma involving the pleura and occurring in association with systemic
      sclerosis. Moreover, this is the second report of a dedifferentiated variant
      among all reported cases of primary lung chondrosarcoma.

PMID- 19593291
TI  - Recovery time in a case of gemfibrozil and simvastatin-associated rhabdomyolysis.
AB  - Simvastatin is a cholesterol-lowering medication heavily prescribed to treat and
      prevent vascular disease. Despite widespread use, cases of simvastatin-induced
      rhabdomyolysis are rare. Little information is available regarding the recovery
      period for a patient who has experienced drug-induced rhabdomyolysis. We present
      a case involving a patient with multiple risk factors (advanced age, high-dose
      simvastatin therapy, concomitant nonsteroidal anti-inflammatory medication, and
      concomitant gemfibrozil therapy) and highlight his recovery course.

PMID- 19593292
TI  - Clavicular tuberculosis following trivial trauma.
AB  - Tuberculosis of the clavicular bone is a very rare clinical entity, with limited
      cases reported in the United States. Furthermore, sparing of the sternoclavicular
      joint is exceedingly unusual. A literature review of the prevalence of clavicular
      tuberculosis identified fewer than 80 cases reported since the discovery of the
      tubercular bacillus, over a century ago. To our knowledge, there have been no
      cases reported over the last decade in the United States. A rare case of
      tuberculous osteomyelitis of the clavicle in an immunocompetent patient who
      presented with swelling of the upper chest is reported.

PMID- 19593293
TI  - How to resolve the conflict within the Medicaid and managed care marriage.

PMID- 19593295
TI  - Infant health outcomes associated with voluntary health care model change in a
      choice-based Medicaid system.
AB  - BACKGROUND: Medicaid health plan enrollment changes may be a barrier to optimal
      care and may increase costs. METHODS: Data represented 45,768 infants enrolled in
      Medicaid in South Carolina, 2000-2002. We examined associations between health
      plan changes and preventive health care, sick infant doctor visits, emergency
      department (ED) visits, and hospitalizations. RESULTS: In adjusted results,
      compared to infants without plan changes, those with changes averaged 40% fewer
      preventive health visits (P <0.001), over 35% fewer sick infant doctor visits (P
      < 0.01), 77% more hospitalizations in year one (P <0.001), and 43% more
      potentially preventable hospitalizations in year one (P <0.01). CONCLUSIONS:
      Infants on Medicaid with a health plan change have less preventive health care,
      are much less likely to be treated for illness in physicians' offices, and have
      substantially more costly medical care. These results may be due to unmeasured
      maternal or family characteristics, or care continuity loss. Plan changes may
      indicate higher infant health risks.

PMID- 19593296
TI  - Isopropyl alcohol ingestion presenting as pseudorenal failure due to acetone
      interference.
AB  - Isopropyl alcohol is a relatively common source of clinical intoxication. It is
      usually suspected when a patient presents with high serum or urine ketones and a
      high osmolar gap without acidosis. Acute renal failure due to isopropyl alcohol
      ingestion is rare. We describe a patient with isopropyl alcohol ingestion who
      presented with renal failure, but with a false elevation of serum creatinine
      secondary to interference by acetone with the colorimetric assay for creatinine.
      We highlight the use of blood gas analyzers, which use an enzymatic assay, thus
      avoiding acetone interference, as a quick method to correctly estimate the serum
      creatinine concentration and avoid labeling the patient as having acute renal
      failure.

PMID- 19593297
TI  - Multiple cranial nerve involvement caused by Brucella melitensis.
AB  - A case of neurobrucellosis complicated by optic, abducens and vestibulocochlear
      nerve palsies is reported. Brucella melitensis was isolated in the cerebrospinal
      fluid, and the patient was diagnosed with retrobulbar neuritis. Despite medical
      treatment, the patient developed optic atrophy. Multiple cranial nerve
      involvement should be kept in mind in patients presenting with blurred vision and
      double vision, especially in regions where brucellosis is endemic.

PMID- 19593298
TI  - Solitary giant splenic metastasis in a patient with metachronous gastric cancers.
AB  - Splenic metastases from solid tumors are uncommon. They may be observed in a
      context of multivisceral dissemination or as a solitary lesion. We report the
      case of an 80-year-old woman with a history of two metachronous gastric cancers
      treated with distal gastrectomy and resection of the gastric remnant within a
      period of 15 years, who presented with a huge splenic tumor mass three years
      after the second operation. Splenectomy was performed. The resection specimens
      showed a well-circumscribed solid lesion measuring 15 cm in the largest diameter.
      Histology revealed metastatic gastric cancer. The differential diagnosis and
      clinical significance of this rare condition is discussed.

PMID- 19593299
TI  - Evaluation of blunt cervical spine injury.
AB  - Injuries resulting from blunt cervical spine trauma are common problems seen in
      emergency departments and treated by trauma care specialists. Timely and
      appropriate imaging studies are essential to the cervical spine evaluation in the
      trauma patient. Despite advances in imaging techniques, cervical injuries may
      still be missed. Several specialty bodies have published guidelines for the
      evaluation of the cervical spine with slightly differing recommendations. The
      purpose of this review is to summarize the current recommendations for
      radiographic evaluation of patients with blunt cervical spine trauma.

PMID- 19593300
TI  - Disability from "soft" neuropsychiatric sequelae due to frontal lobe injury.
AB  - Each year about 1.5 million people suffer from a traumatic brain injury. Many of
      these are seen in primary care settings and most recover completely. Traumatic
      brain injury can show many signs and symptoms, some of which are readily
      identified and treated. Often the neurobehavioral sequelae appear months to years
      later and can cause long-term disability and impairment in neurobehavioral
      functioning. The rehabilitation of these patients is a long and difficult process
      requiring early identification and proper management. This article reviews the
      importance of recognizing the neurobehavioral consequences of frontal lobe
      injury.

PMID- 19593301
TI  - The third wave--medical tourism in the 21st century.
AB  - The high number of uninsured or underinsured Americans and the spiraling cost of
      healthcare in the United States has spurred growth in patients traveling abroad
      for affordable healthcare, which has become known as medical tourism. It is
      projected to become a $21 billion a year industry by 2011. Overseas prices for
      most procedures, including airfare, are often half the cost of those performed in
      the United States; some procedures are 80% less. International facilities in
      India, Thailand, and elsewhere are obtaining Joint Commission International (JCI)
      accreditation and aggressively marketing to Western customers and insurance
      agencies and advertising high quality standards and personalized service. The
      acceptance of medial tourism is growing, with a recent poll showing more than 40%
      of US healthcare consumers willing to travel abroad for care. Insurance companies
      have begun to integrate foreign care into their coverage, offering discounts to
      patients agreeing to overseas travel. Physician groups have been slow to respond,
      even though estimates are that medical tourism may represent $162 billion in lost
      spending in America by 2012. Some experts think the continued US healthcare cost
      crisis will drive an increase in medical tourism and international competition,
      significantly impacting domestic physicians and hospitals.

PMID- 19593302
TI  - Health insurance and the development of diabetic complications.
AB  - BACKGROUND: Lack of health insurance can adversely affect access to medical care
      which leads to poor disease outcome. Few studies examine the effects of no
      insurance on the development of diabetes complications. The objective of this
      study was to determine if there is an association between health insurance status
      and the outcome of complications among a group of diabetic patients admitted to a
      teaching hospital on the Texas-Mexico border. METHODS: A retrospective case
      control study was conducted over a one-year period. Multiple imputations were
      used to address missing values. We examined 82 diabetics who had one or more
      complications and 83 diabetic controls without complications. A complication was
      defined as a current skin or soft-tissue infection or a limb amputation. The main
      exposure was health insurance status, a three-level variable: no health
      insurance, Medicaid, and other insurance (referent). Logistic regression was used
      to calculate health insurance odds ratios (OR) adjusted for age, sex, and a
      history of recent trauma. RESULTS: Patients with no health insurance were twice
      as likely to have a diabetic complication as patients in the referent category:
      adjusted OR = 2.22, P = 0.03. An association between Medicaid status and
      complications was not detected (adjusted OR = 1.16, P = 0.78). CONCLUSIONS: Not
      having health insurance was a risk factor for developing diabetic complications
      in a group of predominantly Hispanic patients.

PMID- 19593303
TI  - Radiological evaluation of blunt cervical spine injury.

PMID- 19593305
TI  - Sun worship can kill common sense.

PMID- 19593306
TI  - Six-point plan could help fast track cancer patients.

PMID- 19593307
TI  - Evidence-based care for patients undergoing coronary angiography.
AB  - Coronary heart disease is the most common cause of death in the United Kingdom,
      accounting for approximately 94,000 deaths per year (Allender et al, 2008).
      Coronary angiography is currently regarded as the gold standard technique for
      evaluation of patients with suspected coronary heart disease and for defining
      coronary anatomy (Di Mario and Sutaria, 2005; Edmond et al, 2008). When caring
      for patients undergoing coronary angiography, it is essential to ensure that all
      aspects of nursing care are evidence-based so that the nurse can perform safe and
      accountable practice (NMC, 2008). The aim of this article is to update the
      nurse's knowledge and skills on caring for a patient undergoing coronary
      angiography. The indications, contra-indications and complications will be
      reviewed. All aspects of nursing care and patient education will be discussed and
      a rationale for nursing actions will be provided.

PMID- 19593308
TI  - Hypertension - a contemporary approach to nursing care.
AB  - The incidence of hypertension is increasing as the number of patients with
      obesity and diabetes mellitus increases. Hypertension results when the peripheral
      vascular resistance is increased, the blood viscosity is elevated and/or the flow
      of blood through the main arteries is impeded. Chronic hypertension results in an
      enlarged heart, myocardial damage and lung and renal abnormalities. While some
      causative factors, such as obesity, can be controlled, others, for example
      genetics, are more difficult to treat because often there is more than one factor
      involved. This article explores how essential and secondary factors contribute to
      the incidence of hypertension and the physiological changes resulting from raised
      blood pressure. It proposes that although traditional treatment has some success,
      nurse-led clinics are having better success not only in controlling raised blood
      pressure but also in reducing cardiac, pulmonary and renal morbidity. Nurse-led
      clinics are more cost-effective, staff are more productive and clients are more
      compliant with treatment.

PMID- 19593309
TI  - Cultural and religious beliefs in stoma care nursing.
AB  - Health-care delivery does not happen in a vacuum. Health is very much part of a
      persons life that also incorporates upbringing, culture and faith. One challenge
      in stoma care is to achieve a high level of care that meets the needs of all
      patients in a multicultural society. Knowledge of cultural differences is
      essential if sensitivity and competence are to be provided. The way people feel
      about themselves and others and their openness to learn about different cultures
      are central to cultural sensitivity. Cultural diversity is a fact of life. As the
      world responds to easier and faster global travel it is inevitable that nurses
      will meet and care for people from different countries. In a multicultural, multi
      faith society, it is essential that care is offered in a way that respects and
      accommodates everyone's cultural and religious needs.

PMID- 19593310
TI  - Using a reflective framework to assess skills - taking a manual BP.
AB  - This article explores the skill of taking a manual blood pressure (BP) using a
      stethoscope and sphygmomanometer. Achieving competence in this area has become
      more difficult since the introduction of electronic BP monitors and less
      opportunity to practice manually. A reflective framework was used to guide the
      authors thoughts and actions related to this skill, as they learned how to
      competently undertake it. A particular learning style, which the authors
      identified as helpful is also discussed.

PMID- 19593311
TI  - Prevalence rates and comparisons of obesity levels in Ireland.
AB  - This article compares the prevalence of the overweight and obesity levels in
      Irish school children aged 4-13 years from data collected by one of the authors
      in 2007, with data collected from a previous Irish study in 2002 by Whelton et al
      (2007). Both data sets were analyzed using the International Obesity Taskforce
      (IOTF) international cut-off points for body mass index (BMI). From the data
      collected in 2007 the overall prevalence of the overweight was 17.8% and the rate
      of obesity was 6.8%. The prevalence of the overweight and obese was 24.6%. No
      correlation was found between gender and BMI, however a positive and significant
      correlation was observed between age and BMI, indicating that as age increased so
      too did BMI (R = 0.35, p < 0.001). Comparing results with data from 2002 (Whelton
      et al, 2007), no statistically significant changes in the proportions of
      overweight and obese children were observed within this age group in the 5-year
      period from 2002 to 2007. While the results of our data suggest that rates of
      being overweight or obese among Irish children in this age group may be
      stabilizing, larger and preferably longitudinal Irish studies are required if
      this assertion is to be fully validated in the Irish context.

PMID- 19593312
TI  - Interprofessional capacity building in diabetic foot management.
AB  - The need to build capacity between allied health practitioners in the management
      of the diabetic foot is becoming increasingly important as the number of people
      diagnosed with diabetes mellitus rises globally each year. This rise in newly
      diagnosed patients, who often present asymptomatically, highlights the need for a
      significant shift in emphasis from simply treating those with long-term
      complications of the condition. Incorporation of public health initiatives to
      promote awareness and prevention of the potential decline in functional and
      emotional health, and the subsequent decreased quality of life in later years,
      must become the responsibility of health professionals, who are able to break
      down interdisciplinary barriers at the level of patient interaction.
      Traditionally, long-term macrovascular and microvascular manifestations of
      diabetes mellitus have led to a convenient division of care for people with
      diabetes between the health professions. As the evidence base increases to
      suggest a more holistic impact of the condition on general health, the need to
      build capacity within and between professions in the management and prevention of
      future disease processes has never been clearer. This article highlights key
      issues in the management of the diabetic foot, which are of paramount
      significance in the emergence, development and maintenance of interdisciplinary
      professional relationships.

PMID- 19593313
TI  - Exploring mental health students' perceptions of role models.
AB  - This article describes and reflects on a qualitative study that attempted to
      develop further understanding of the concept of role models, using the
      experiences of third-year students undertaking mental health nurse education.
      Although there is a wealth of literature regarding role models, little exists
      that acknowledges what, in this case, students want of a role model, or how the
      students identify the positive attributes of a significant role model. The
      researcher used a qualitative approached based on phenomenological methods. The
      research question used, was: 'From the viewpoint of a third-year student
      undertaking mental health nurse education, what is the phenomenon referred to as
      role model?'

PMID- 19593314
TI  - Investigating the role and impact of expert nurses.
AB  - This literature review was conducted to identify the attributes of an expert
      nurse and the direct and indirect impact they have on patient care, health-care
      organisations and nursing. Given the loss of expert nursing posts as a result of
      NHS deficits, there is an urgent need to differentiate between a range of expert
      nursing roles and how these contribute to positive patient and health outcomes
      and organisational efficiency. The focus of the literature search was on
      developments in the UK and the results indicated that ambiguity and confusion
      exist around the terminology and definitions associated with expert nurses.
      Research shows that expert nurses have a positive impact on patient care and
      organisational efficiency. However, a lack of clarity leads to a dilution of
      expert nursing roles and nurse expertise. There is a need for national guidance
      on the skills required of expert nurses and the necessity of considering the
      formal protection of nursing titles.

PMID- 19593316
TI  - Sick-room helpers - the first health-care assistants.

PMID- 19593315
TI  - Factual and legal causation - their relation to negligence in nursing.
AB  - Several elements must be shown to be fulfilled for a court to hold that
      negligence has occurred, and a person is liable. One of these elements is
      'causation', the idea that there must be a causal link between the claimant's
      loss and the negligent behaviour of the defendant. This article considers the
      application of the tests of factual and legal causation to cases of medical
      negligence. It is argued that in light of the recent development of a number of
      exceptional approaches to factual causation, each relating to a particular causal
      problem, the causal process must be identified in any given case so that the
      correct test for factual causation can be applied. This is illustrated by
      reference to MRSA claims. It is further argued that where the negligence consists
      of misdiagnosis or mistreatment of existing illness the causal problem is unique
      to medical negligence and demands a unique approach to causation. The 'scope of
      duty' test for legal causation is illustrated in a medical context and it is
      argued that where the negligence consists of a failure to warn the patient of the
      risks involved in treatment, although the harm is clearly within the scope of the
      doctor's duty, it is wrong to establish liability in the absence of factual
      causation.

PMID- 19593317
TI  - Knowing what to do in a fire is every nurse's responsibility.

PMID- 19593318
TI  - Updating the assessment of cardiac risk: beyond Framingham.
AB  - Identification of the widely accepted cardiovascular risk factors of age, sex,
      hypertension, hyperlipidemia, smoking, obesity, diabetes, and physical inactivity
      from the Framingham Heart Study have led to dramatic reductions in cardiovascular
      morbidity and mortality. The Framingham estimation of coronary heart disease
      remains the mainstay of clinical risk assessment. However, novel risk predictors
      present opportunities to identify more patients at risk and to more accurately
      define that risk. Such predictors include lipoprotein analysis, measurement of
      lipoprotein-associated phospholipase A(2) and C-reactive protein, and assessment
      of hyperglycemia, liver function, and central obesity. Vascular imaging can also
      provide useful risk information. Using Framingham as a basis, several
      international groups have developed risks-coring systems that more closely
      reflect their individual populations and the clinical practicalities of their
      countries. When used accordingly, the newer risk predictors build upon the
      Framingham framework to allow physicians and their patients to effectively
      minimize, or even avoid, the burden of cardiovascular disease.

PMID- 19593319
TI  - Improving adjunctive pharmacotherapy for primary percutaneous coronary
      intervention in ST-segment elevation myocardial infarction: beyond the HORIZONS
      AMI trial.
AB  - Patients who present with acute coronary syndromes, particularly ST-segment
      elevation myocardial infarction (STEMI), have abnormalities in platelet size and
      function that predispose to thrombotic events. Both preprocedural platelet
      reactivity and mean platelet volume are directly correlated with the occurrence
      of adverse ischemic events and impaired microvascular reperfusion following
      primary percutaneous coronary intervention (PCI) for STEMI. The Harmonizing
      Outcomes with Revascularization and Stents in Acute Myocardial Infarction
      (HORIZONS-AMI) trial demonstrated a similar ischemic event rate to 30 days with a
      significantly lower bleeding event rate (enhanced net clinical benefit) in favor
      of bivalirudin monotherapy (with provisional platelet glycoprotein [GP] IIb/IIIa
      receptor blockade) in comparison with unfractionated heparin plus GP IIb/IIIa
      blockade in patients undergoing primary PCI for STEMI. The bivalirudin
      monotherapy was associated with a highly significant greater incidence of acute
      stent thrombosis. This observation provides the opportunity for strategies that
      enhance periprocedural platelet inhibition to reduce stent thrombosis and to
      potentially improve the safety and efficacy of periprocedural adjunctive
      pharmacotherapy above that achieved by bivalirudin monotherapy alone.

PMID- 19593320
TI  - Polycystic ovary syndrome: a major unrecognized cardiovascular risk factor in
      women.
AB  - The prevalence of polycystic ovary syndrome (PCOS) is estimated to be nearly 10%
      among reproductive age women. PCOS may represent the largest underappreciated
      segment of the female population at risk of cardiovascular disease. Clinicians
      providing care to women of childbearing age must recognize the presenting clues,
      including irregular menses, hirsutism, alopecia, hyperandrogenemia, and obesity.
      The pathophysiology of PCOS is complex, involving the hypothalamus-pituitary
      ovarian axis, ovarian theca cell hyperplasia, hyperinsulinemia, and a multitude
      of other cytokine- and adipocyte-driven factors. Cardiac risk factors associated
      with PCOS have public health implications and should drive early screening and
      intervention measures. There are no consensus guidelines regarding screening for
      cardiovascular disease in patients with PCOS. Fasting lipid profiles and glucose
      examinations should be performed regularly. Carotid intimal medial thickness
      examinations should begin at age 30 years, and coronary calcium screening should
      begin at age 45 years. Treatment of the associated cardiovascular risk factors,
      including insulin resistance, hypertension, and dyslipidemia, should be
      incorporated into the routine PCOS patient wellness care program.

PMID- 19593321
TI  - The JUPITER trial: How will it change clinical practice?
AB  - Several studies have shown that baseline levels of high-sensitivity C-reactive
      protein (hs-CRP) in apparently healthy men and women are predictive of future
      cardiovascular events. In primary prevention, hs-CRP levels could indicate which
      primary prevention patients are at higher risk and might benefit from preventive
      statin therapy. Justification for the Use of Statins in Primary Prevention: An
      Intervention Trial Evaluating Rosuvastatin (JUPITER) aimed to determine whether
      treatment with rosuvastatin 20 mg/d would reduce the rate of first major
      cardiovascular events among apparently healthy individuals with low-density
      lipoprotein cholesterol (LDL-C) levels below 130 mg/dL, but with hs-CRP levels of
      2 mg/L or higher. At the time of study closure, it was found that treatment with
      rosuvastatin significantly reduced the primary composite endpoint by 44% as
      compared with placebo. Results of the JUPITER trial clearly suggest that patients
      with elevated hs-CRP stand to benefit from statin therapy, regardless of their
      LDL-C level.

PMID- 19593322
TI  - Quality first.

PMID- 19593324
TI  - AACC: a new designation.

PMID- 19593323
TI  - American college of cardiology health system reform summit.

PMID- 19593326
TI  - Cardiac risk - coronary calcium scoring for all?

PMID- 19593327
TI  - Murine renal transplantation procedure.
AB  - Renal orthotopic transplantation in mice is a technically challenging procedure.
      Although the first kidney transplants in mice were performed by Russell et al
      over 30 years ago (1) and refined by Zhang et al years later (2), few people in
      the world have mastered this procedure. In our laboratory we have successfully
      performed 1200 orthotopic kidney transplantations with > 90% survival rate. The
      key points for success include stringent control of reperfusion injury, bleeding
      and thrombosis, both during the procedure and post-transplantation, and use of 10
      0 instead of 11-0 suture for anastomoses. Post-operative care and treatment of
      the recipient is extremely important to transplant success and evaluation. All
      renal graft recipients receive antibiotics in the form of an injection of
      penicillin immediately post-transplant and sulfatrim in the drinking water
      continually. Overall animal health is evaluated daily and whole blood creatinine
      analyses are performed routinely with a portable I-STAT machine to assess graft
      function.

PMID- 19593329
TI  - Urothelial carcinoma with villoglandular differentiation: a study of 14 cases.
AB  - Tumors of the urinary bladder may have a variety of histological patterns. Tumors
      with either glandular or villous features, such as villous adenomas, in situ
      adenocarcinomas, invasive adenocarcinomas, and variants of urothelial carcinoma
      such as micropapillary carcinomas have been described. However, urothelial
      carcinomas with both villous and glandular features have not been well
      characterized. We identified 14 cases of urothelial carcinoma with villoglandular
      differentiation. These cases were defined as having villoglandular features if
      they contained superficial finger-like processes lined by epithelium having true
      glandular lumina. Mean patient age at presentation was 70 years (range: 46-84
      years) with a male predominance (5:1). A total of 3 cases (21%) were non
      invasive, five cases (36%) had lamina propria invasion, five cases (36%) had
      muscularis propria invasion and one case (7%) had extravesicular extension. A
      concurrent high-grade papillary urothelial carcinoma component was identified in
      11 cases (79%), micropapillary component in 5 (36%) cases, in-situ urothelial
      carcinoma component in 3 cases (21%), plasmacytoid component in 3 cases (21%),
      invasive adenocarcinoma in 2 cases, sarcomatoid carcinoma component in one case
      (14%), and small-cell carcinoma component in 1 case (7%). Cystitis cystica et
      glandularis was present in 3 cases (21%). Angiolymphatic invasion was identified
      in 3 cases (21%). Histologically, the villoglandular components were composed of
      finger-like processes lined by glands intimately admixed with high-grade
      urothelial carcinoma. Many of the glands had cribriform features lined by non
      mucin producing cuboidal to columnar cells. Urothelial carcinoma with
      villoglandular differentiation are high-grade tumors typically seen in elderly
      males, characterized by superficial filliform processes lined by glands
      intimately admixed with high-grade urothelial carcinoma (in situ or invasive) and
      other aggressive variants of urothelial carcinoma. These relatively rare tumors
      should be recognized as a variant of urothelial carcinoma.

PMID- 19593328
TI  - Sonic hedgehog signaling proteins and ATP-binding cassette G2 are aberrantly
      expressed in diffuse large B-cell lymphoma.
AB  - Dysregulation of the sonic hedgehog (SHH) signaling pathway has been shown in
      several cancer types, but has not been explored in diffuse large B-cell lymphoma.
      We assessed 67 cases of diffuse large B-cell lymphoma for expression of SHH
      (ligand), GLI1, GLI2 and GLI3 (transcriptional effectors of SHH signaling), and
      the ATP-binding cassette (ABC)G2 (a downstream target of SHH signaling), using
      immunohistochemistry. For comparison, we assessed the expression levels of these
      proteins in 28 cases of follicular lymphoma, 5 chronic lymphocytic leukemia/small
      lymphocytic lymphoma, and 5 reactive lymph nodes. In diffuse large B-cell
      lymphoma, SHH was expressed in 61 of 67 (91%) cases, GLI1 in 62 of 67 (93%), GLI2
      in 41 of 56 (73%), and GLI3 in 22 of 56 (39%). Expression of ABCG2 was detected
      in 52 of 55 (95%) cases and was high in 15 (27%) cases. SHH expression positively
      correlated with expression levels of ABCG2 (P=0.05). Patients with diffuse large
      B-cell lymphoma with high ABCG2 expression showed significantly shorter overall
      survival (P=0.031) and failure-free survival (P=0.029) compared with patients
      with tumors with low or no expression of ABCG2. Diffuse large B-cell lymphomas
      expressed SHH, and GLI1, GLI2, and GLI3 more frequently and more intensely than
      cases of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic
      lymphoma. In conclusion, our data show that SHH signaling proteins and ABCG2 are
      aberrantly expressed in diffuse large B-cell lymphoma and that ABCG2 expression
      has prognostic implications. These findings also provide evidence that
      dysregulation of the SHH pathway may be involved in the pathogenesis of diffuse
      large B-cell lymphoma.

PMID- 19593330
TI  - Sequential P3 effects in a Posner's spatial cueing paradigm: trial-by-trial
      learning of the predictive value of the cue.
AB  - The neurocognitive consequences of correct or incorrect spatial prediction in a
      sequential S1-S2 paradigm were assessed. Sequential dependence on previous trial
      outcome (valid or invalid) was assessed by late Event-Related Potentials (ERPs)
      and behavioral responses. Two different experiments were performed, situating the
      target in the vertical (Experiment 1) or in the horizontal (Experiment 2)
      meridian. RTs and late positivities (P3a and P3b) were recorded. ERPs showed that
      posterior positivity (probably a P3b) was greater in invalid-valid trials than in
      valid-valid trials but lower than in valid-invalid trials. However, at the
      frontal electrodes, late positivity (probably a P3a) only appeared in valid
      invalid trials, indicating that invalid trials are analyzed as novel-like
      stimuli. The P3b results suggest trial-by-trial learning of the predictive value
      of the cue, which needs to be updated as indicated by the pattern of P3b
      amplitudes: valid-invalid > invalid-valid > valid-valid.

PMID- 19593331
TI  - Reduction of the number of new cells reaching olfactory bulbs impairs olfactory
      perception in the adult opossum.
AB  - In adult mammals cells generated in the subventricular zone (SVZ) migrate to
      olfactory bulbs (OB). Functional significance of this continuous neurogenesis is
      not clear. We injected opossums (Monodelphis domestica) for seven consecutive
      days with a 5HT(1A) agonist (8-OH-DPAT or buspirone) or its antagonist WAY100635.
      One hour after each of these injections bromodeoxyuridine (BrdU) a marker of
      dividing cells was also injected. Two months later, when newly generated neurons
      settled in the OB and matured the ability of these opossums to detect hidden food
      by olfactory cues was tested. Afterwards, numbers of BrdU-labeled cell nuclei in
      their OB were counted and a phenotype of labeled cells established. In all groups
      investigated the majority of new cells differentiated into neurons (55-76%) and a
      lower proportion into astroglia (6-12%). Numbers of BrdU-labeled cells differed
      depending on the applied treatment: both agonists of the 5HT(1A) receptor
      increased these numbers, while its antagonist decreased them. The increased
      number of new OB interneurons did not change the time required for finding all
      three food items and therefore did not improve the opossums' performance in this
      test of the olfactory perception. However, opossums that had the reduced number
      of new generated OB cells searched longer for each food item and in consequence
      took three times longer to find all three crickets, than did opossums from other
      groups. In conclusion, lower numbers of new neurons in the opossums OB correlated
      with their worse behavioral performance in a test based on olfactory perception.

PMID- 19593333
TI  - A prospective study of prenatal mercury exposure from maternal dental amalgams
      and autism severity.
AB  - Dental amalgams containing 50% mercury (Hg) have been used in dentistry for the
      last 150 years, and Hg exposure during key developmental periods was associated
      with autism spectrum disorders (ASDs). This study examined increased Hg exposure
      from maternal dental amalgams during pregnancy among 100 qualifying participants
      born between 1990-1999 and diagnosed with DSM-IV autism (severe) or ASD (mild).
      Logistic regression analysis (age, gender, race, and region of residency
      adjusted) by quintile of maternal dental amalgams during pregnancy revealed the
      ratio of autism:ASD (severe:mild) were about 1 (no effect) for < or =5 amalgams
      and increased for > or =6 amalgams. Subjects with > or =6 amalgams were 3.2-fold
      significantly more likely to be diagnosed with autism (severe) in comparison to
      ASD (mild) than subjects with < or =5 amalgams. Dental amalgam policies should
      consider Hg exposure in women before and during the child-bearing age and the
      possibility of subsequent fetal exposure and adverse outcomes.

PMID- 19593332
TI  - The effect of alpha-tocopherol in the acute ethanol intake and its withdrawal on
      penicillin-induced epilepsy.
AB  - The present study was designed to investigate the influence of acute ethanol
      intake and its withdrawal on the anticonvulsant effect of alpha-tocopherol in
      penicillin-induced epileptiform activity. Ethanol-treated rats received a daily
      dose of 3 g/kg or 9.0 g/kg of 30% ethanol solution for 3 days. Thirty minutes
      after penicillin injection (500 units, i.c.) the most effective dose of alpha
      tocopherol (500 mg/kg) was administered intramuscularly (i.m.). Acute
      administration of ethanol, in a dose of 3 g/kg, did not change either frequency
      or amplitude of penicillin-induced epileptiform activity, while dose of 9 g/kg
      ethanol significantly decreased the mean frequency of penicillin-induced
      epileptiform ECoG activity in the ethanol-treated group. Ethanol (9 g/kg)
      withdrawal also caused an increase in the amplitude of epileptiform ECoG activity
      in the withdrawal group. The results suggest that acute administration of high
      dose ethanol (9 g/kg) and alpha-tocopherol have some limited anticonvulsive
      effects in penicillin-induced epileptiform activity in rats.

PMID- 19593334
TI  - Regional differences in the vulnerability of substantia nigra dopaminergic
      neurons in weaver mice.
AB  - Vulnerability of midbrain dopaminergic (DA) neurons in the weaver mouse was
      studied at postnatal (P) days 8 and 90, in chosen coronal levels throughout the
      anteroposterior (AP) extent of the substantia nigra pars compacta (SNc). Wild
      type (+/+) and homozygous weaver (wv/wv) mice used were the offspring of pregnant
      dams injected in several cases with tritiated thymidine on embryonic days 11-15.
      DA neurons were identified for their tyrosine hydroxylase immunoreactivity. Data
      reveal that at P8, the frequency of both +/+ and wv/wv late-generated DA cells
      increases from rostral to caudal SNc. No apparent DA-cell loss was observed at P8
      in the mutant genotype, irrespective of the AP level considered. However,
      throughout the AP, there was a significant reduction in the number of these
      neurons at any level in 90-day-old weavers. Comparison of P8 and P90 +/+ SNc
      suggests that cell death is not a major aspect in the developmental regulation of
      normal DA neurons, although numerical cell depletion in the postnatal development
      of weaver SNc probably results from the amplification of a basal cell-death
      process, which affected all the coronal levels studied.

PMID- 19593335
TI  - In vitro-evaluation of lipid emulsions as vehicles for the administration of
      xenon: interaction with NMDA receptors.
AB  - The noble gas xenon is an antagonist of the NMDA (N-methyl-D-aspartate)-type
      glutamate receptor which may account for the ideal anesthetic profile and potent
      neuroprotective properties demonstrated even at subanesthetic concentrations.
      Because lipid emulsions also promote NMDA antagonistic effects they may serve as
      ideal carriers for xenon. In this in vitro study, we investigated the efficacy of
      xenon dissolved in various lipid emulsions (Intralipid, Lipofundin, ClinOleic and
      Abbolipid on NMDA-evoked currents in cultured cortical neurons. The NMDA receptor
      blocking property at a clinically relevant concentration seen in the lipid
      emulsions tested may contribute to the anesthetic, analgetic and neuroprotective
      effects of xenon administered by way of these lipid carriers. Abbolipid? may
      serve as the most acceptable carrier since the NMDA antagonistic effect of xenon
      was enhanced in combination with this emulsion.

PMID- 19593336
TI  - Pharmacological and biochemical effects of Ginkgo biloba extract on learning,
      memory consolidation and motor activity in old rats.
AB  - Effect of administration of the standardized extract of Ginkgo biloba leaves (EGb
      761) on learning, memory and exploratory behavior was estimated in water maze and
      hole-board tests. Rats (18-month old) received for three months EGb 761 at doses:
      50, 100 and 150 mg/kg b.w. per day. After completion of the behavioral
      experiment, concentrations of neurotransmitters were estimated in selected brain
      regions. ANOVA demonstrated significant differences in the content of monoamines
      and metabolites between the treatment groups compared to the control. The
      increased level of 5-hydroxytryptamine (5-HT) in the hippocampus and 5-HIAA (5-HT
      metabolite) in the prefrontal cortex correlated positively with the retention of
      spatial memory. Positive correlation between platform crossings in SE during the
      probe trial and neurotransmitter turnover suggest improvement of spatial memory.
      Long-term administration of Ginkgo biloba extract can improve spatial memory and
      motivation with significant changes in the content and metabolism of monoamines
      in several brain regions.

PMID- 19593337
TI  - Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with a complex etiology
      and pathogenesis. Chromosome missegregation was proposed two decades ago to be
      responsible for neurodegeneration in AD patients. It was speculated that the
      aneuploidy is a result of aberrant cell cycle of neuronal progenitors during
      adult neurogenesis and/or of mature neurons. There is mounting evidence of
      increased rate of general aneuploidy and cell cycle reentry in the AD patients'
      brains, with area-specific pattern. In this review, we discuss the involvement of
      chromosome instability, genome damage and cell cycle impairment in AD pathology.

PMID- 19593338
TI  - Event-related desynchronization and synchronization in evoked K-complexes.
AB  - K-complexes - phenomena occurring in sleep EEG - pose severe challenges in terms
      of detection as well as finding their physiological origin. In this study, K
      complexes (KCs) were evoked by auditory stimuli delivered during sleep. The use
      of evoked KCs enables testing the sleeping nervous system under good experimental
      control. This paradigm allowed us to adopt into the KC studies a method of signal
      analysis that provides time-frequency maps of statistically significant changes
      in signal energy density. Our results indicate that KCs and sleep spindles may be
      organized by a slow oscillation. Accordingly, KCs might be evoked only if the
      stimulus occurs in a certain phase of the slow oscillation. We also observed
      middle-latency evoked responses following auditory stimulation in the last sleep
      cycle. This effect was revealed only by the time-frequency maps and was not
      visible in standard averages.

PMID- 19593339
TI  - Three-dimensional ray tracing on Delaunay-based reconstructed surfaces.
AB  - A method of ray tracing for free-form optical surfaces has been developed. The
      ray tracing through such surfaces is based on Delaunay triangulation of the
      discrete data of the surface and is related to finite-element modeling. Some
      numerical examples of applications to analytical, noisy, and experimental free
      form surfaces (in particular, a corneal topography map) are presented. Ray
      tracing results (i.e., spot diagram root-mean-square error) with the new method
      are in agreement with those obtained using a modal fitting of the surface, for
      sampling densities higher than 40 x 40 elements. The method competes in
      flexibility, simplicity, and computing times with standard methods for surface
      fitting and ray tracing.

PMID- 19593340
TI  - Abel inversion of deflectometric data: comparison of accuracy and noise
      propagation of existing techniques.
AB  - Abel inverse integral to obtain local field distributions from path-integrated
      measurements in an axisymmetric medium is an ill-posed problem with the integrant
      diverging at the lower integration limit. Existing methods to evaluate this
      integral can be broadly categorized as numerical integration techniques,
      semianalytical techniques, and least-squares whole-curve-fit techniques. In this
      study, Simpson's 1/3rd rule (a numerical integration technique), one-point and
      two-point formulas (semianalytical techniques), and the Guass-Hermite product
      polynomial method (a least-squares whole-curve-fit technique) are compared for
      accuracy and error propagation in Abel inversion of deflectometric data. For data
      acquired at equally spaced radial intervals, the deconvolved field can be
      expressed as a linear combination (weighted sum) of measured data. This approach
      permits use of the uncertainty analysis principle to compute error propagation by
      the integration algorithm. Least-squares curve-fit techniques should be avoided
      because of poor inversion accuracy with large propagation of measurement error.
      The two-point formula is recommended to achieve high inversion accuracy with
      minimum error propagation.

PMID- 19593341
TI  - Simultaneous analog and photon counting detection for Raman lidar.
AB  - The Atmospheric Radiation Measurement program Raman lidar was upgraded in 2004
      with a new data system that provides simultaneous measurements of both the
      photomultiplier analog output voltage and photon counts. We describe recent
      improvements to the algorithm used to merge these two signals into a single
      signal with improved dynamic range. The effect of modifications to the algorithm
      are evaluated by comparing profiles of water vapor mixing ratio from the lidar
      with radiosonde measurements over a six month period. The modifications that were
      implemented resulted in a reduction of the mean bias in the daytime water vapor
      mixing ratio from a 3% dry bias to well within 1%. This improvement was obtained
      by ignoring the temporal variation of the glue coefficients and using only the
      nighttime average glue coefficients throughout the entire diurnal cycle.

PMID- 19593342
TI  - Tilted Bragg grating multipoint sensor based on wavelength-gated cladding-modes
      coupling.
AB  - In recent years, tilted fiber Bragg gratings (TFBGs) have been demonstrated to be
      a promising technological platform for sensing applications such as the
      measurement of axial strain, bending, vibration, and refractive index. However,
      complex spectral measurements combined with the difficulty of using TFBGs in a
      quasi-distributed sensors network limit the practical exploitation of this
      assessed technology. To address this issue, we propose a hybrid configuration
      involving uniform and TFBGs working in reflection, which makes the demodulation
      technique easier and allows multipoint sensing. This configuration provides a
      narrowband reflection signal that is modulated by the wavelength selective losses
      associated with some TFBG's cladding-modes resonances. We report here the
      operating principle of the proposed device. An experimental validation is
      presented for refractive-index sensing purposes.

PMID- 19593343
TI  - Low-loss polynomial White cell optical true-time delay engine for wideband radio
      frequency array beam steering.
AB  - An optical true-time delay (OTTD) engine based on a polynomial White cell
      (quadratic) is designed and simulated with commercially available components with
      a time delay increment of at least 25 ps for wideband beam steering in the
      frequency range of 2-18 GHz. The simulated quantification of aberration losses
      show for the first time that aberration losses in the null cell are about 5.0 dB.
      However, for the longer delay arms, there is an additional loss of about 3.2
      dB/delay each time a beam travels an arm with a lens train used as a delay
      element compared with the same delay generated without a lens train. We present a
      design and simulation of a low-loss delay arms quartic cell without a lens train
      by using a separate field lens for each delay arm for efficient wideband beam
      steering.

PMID- 19593344
TI  - Dwell time algorithm in ion beam figuring.
AB  - To get a high-precision optical surface, the deconvolved process of dwell time
      was transferred to a matrix equation in which the damped factor and the extra
      removal amount were introduced to expand the freedom of solution. A path weight
      factor and a surface error weight factor were used to take the scanning path and
      the initial surface error into account. Combined with the Gerchberg bandlimited
      extrapolation algorithm for initial surface error map extension, a high-precision
      final surface could be obtained within a factual aperture. Two surface error maps
      were calculated to rms = 0.1 nm from rms = 130.23 nm and to rms = 0.08 nm from
      rms = 82.74 nm. The simulations show that a perfect dwell time solution could be
      obtained by the revised matrix equation and initial surface error map extension
      with the help of the least squares QR (LSQR) algorithm.

PMID- 19593345
TI  - Frequency characteristics of an inherently stable Nd:YAG laser operated at liquid
      helium temperature.
AB  - We report on frequency measurements of a free-running Nd:YAG laser operating at
      temperatures down to 6.5 K using a femtosecond laser frequency comb. Due to lower
      thermal expansion and thermo-optic effects as well as reduced electron-phonon
      interactions in Nd:YAG at cryogenic temperatures, a laser frequency stability on
      the order of 10(-11) at tau < or = 30s has been achieved. Within a one-week
      measurement period, absolute frequency deviations were lower than 1.85 MHz. This
      is up to a 100-fold improvement of frequency stability compared to any existing
      free-running solid-state laser.

PMID- 19593346
TI  - Squeezed lattice elliptical-hole terahertz fiber with high birefringence.
AB  - A highly birefringent elliptical-hole terahertz (THz) fiber with a squeezed
      lattice is proposed. This THz fiber is formed through regular linear deformation
      of a circular porous fiber by squeezing it in one direction, which may be
      fabricated with the existing fabrication technology. By numerical analysis we
      show that, with a moderate amount of deformation, the proposed THz fiber can
      exhibit high birefringence on a level of 10(-2) over a wide THz frequency range.
      And the THz fiber guiding loss caused by material absorption can be reduced
      effectively, since a dominant fraction of modal power is distributed in the
      airholes inside the dielectric material.

PMID- 19593347
TI  - Suppressing phase errors from vibration in phase-shifting interferometry.
AB  - A general method for reducing the influence of vibrations in phase-shifting
      interferometry corrects the surface phase map through a spectral analysis of a
      "phase-error pattern," a plot of the interference intensity versus the measured
      phase, for each phase-shifted image. The method is computationally fast,
      applicable to any phase-shifting algorithm and interferometer geometry, has few
      restrictions on surface shape, and unlike spatial Fourier methods, high density
      spatial carrier fringes are not required, although at least a fringe of phase
      departure is recommended. Over a 100x reduction in vibrationally induced surface
      distortion is achieved for small amplitude vibrations on real data.

PMID- 19593348
TI  - Transmission-grating-based wavefront tilt sensor.
AB  - We propose a new type of tilt sensor. It consists of a grating and an image
      sensor. It detects the tilt of the collimated wavefront reflected from a plane
      mirror. Its principle is described and analyzed based on wave optics.
      Experimental results show its validity. Simulations of the ordinary
      autocollimator and the proposed tilt sensor show that the effect of noise on the
      measured angle is smaller for the latter. These results show a possibility of
      making a smaller and simpler tilt sensor.

PMID- 19593349
TI  - Approach to nonparametric cooperative multiband segmentation with adaptive
      threshold.
AB  - We present a new nonparametric cooperative approach to multiband image
      segmentation. It is based on cooperation between region-growing segmentation and
      edge segmentation. This approach requires no input data other than the images to
      be processed. It uses a spectral homogeneity criterion whose threshold is
      determined automatically. The threshold is adaptive and varies depending on the
      objects to be segmented. Applying this new approach to very high resolution
      satellite imagery has yielded satisfactory results. The approach demonstrated its
      performance on images of varied complexity and was able to detect objects of
      great spatial and spectral heterogeneity.

PMID- 19593350
TI  - Dispersion compensation in moving-optical-wedge Fourier transform spectrometer.
AB  - In this paper we study the effect of material dispersion on the performance of a
      moving-optical-wedge Fourier transform spectrometer. The spectrum is thus
      evaluated numerically using a test spectrum source. The obtained numerical
      results show that the classical technique for numerical dispersion compensation,
      usually used with a Michelson interferometer, cannot be efficiently used with
      wedge interferometers as it is limited to the cases of weak dispersion. The error
      in this technique is thus evaluated in different cases and a new numerical
      technique is proposed to overcome this error. We also notice shrinkage in the
      interferogram spread in the spatial domain in contradiction with the normal
      dispersion effect in a Michelson interferometer.

PMID- 19593351
TI  - Wind-bias correction method for narrowband sodium Doppler lidars using iodine
      absorption spectroscopy.
AB  - We present a technique to measure the frequency chirp introduced by the laser
      pulse amplification process in the transmitter of the Colorado State University
      sodium lidar system. This chirp causes a systematic radial wind bias that must be
      removed from the reported wind measurements. An iodine absorption line located
      near the lidar operating wavelength of 589.16 nm is used for real-time monitoring
      and measurement of the chirp for the correction of radial wind bias. This
      technique has been thoroughly characterized in the laboratory and validated by
      field testing, facilitating simultaneous measurements of temperature and
      horizontal wind in the mesopause region of the atmosphere (80-105 km).

PMID- 19593352
TI  - Space division multiplexing high-birefringence-fiber loop mirrors for
      discriminative measurement of temperature and strain.
AB  - We present a fiber sensor scheme for discriminative measurement of temperature
      and strain by space division multiplexing high-birefringence-fiber loop mirrors
      (HBFLMs). Discriminative measurement of temperature and strain can be realized by
      sequentially measuring the resonance wavelength shifts of two HBFLMs constructed
      with the same high-birefringence fiber. Experimental results show that the
      temperature and strain resolutions reach +/-0.5 degrees C and +/-10 microepsilon,
      respectively. This scheme can provide not only high resolutions in temperature
      and strain but also has potential applications in distributed HBFLM sensing.

PMID- 19593353
TI  - Optimization of axial resolution in a confocal microscope with D-shaped
      apertures.
AB  - We show theoretically that the axial resolution is improved when two
      centrosymmetric D-shaped apertures are combined in a confocal microscope with a
      finite-sized pinhole. The optimum width of a divider that separates the D-shaped
      apertures to give the maximum axial resolution for a given pinhole size is
      investigated, and the magnitude of the signal level is explored.

PMID- 19593354
TI  - Characterization of a spatial light modulator and its application in phase
      retrieval.
AB  - Recently a phase retrieval method using a movable phase plate as modulator has
      been proposed [Phys. Rev. A75, 043805 (2007)]. This method is applicable to
      general complex-valued fields and exhibits rapid convergence and high robustness
      to noise. In this paper, we demonstrate how to use this technique to characterize
      the phase shifting properties of a liquid-crystal modulator, and in turn we use
      the characterized modulator as the modulation device in the presented phase
      retrieval method. The adoption of a dynamic modulator gives a much more robust
      and flexible setup.

PMID- 19593356
TI  - Wavefront reconstruction over a circular aperture using gradient data
      extrapolated via the mirror equations.
AB  - Methods for extrapolating gradient data outside a circular aperture from
      measurements obtained within a circular aperture are presented. The proposed
      methods are required to be computationally efficient and to avoid the excitation
      of additional waffle modes in Fried alignment. It is shown that, using an octagon
      as an intermediate step from the circle to the square in the extrapolation
      process, the computations or residual reconstruction error can be reduced. The
      resulting computational cost is as low as O(N(1/2)), where N is the number of
      measurement points. The performances of the extrapolation methods are studied in
      connection with a recently developed O(N) wavefront reconstruction algorithm
      based on wavelet filter banks [IEEE J. Sel. Top. Signal Process. 2, 781 (2008)]
      Experiments indicate that, as expected, there is a significant reconstruction
      error if no extrapolation is used. Further, the proposed extrapolation techniques
      lead to a reconstruction with data that are marginally different from a pupil
      masked reconstruction using data from a square aperture.

PMID- 19593355
TI  - Ultrabroadband coherence-domain imaging using parametric downconversion and
      superconducting single-photon detectors at 1064 nm.
AB  - Coherence-domain imaging systems can be operated in a single-photon-counting
      mode, offering low detector noise; this in turn leads to increased sensitivity
      for weak light sources and weakly reflecting samples. We have demonstrated that
      excellent axial resolution can be obtained in a photon-counting coherence-domain
      imaging (CDI) system that uses light generated via spontaneous parametric
      downconversion (SPDC) in a chirped periodically poled stoichiometric lithium
      tantalate (chirped-PPSLT) structure, in conjunction with a niobium nitride
      superconducting single-photon detector (SSPD). The bandwidth of the light
      generated via SPDC, as well as the bandwidth over which the SSPD is sensitive,
      can extend over a wavelength region that stretches from 700 to 1500 nm. This
      ultrabroad wavelength band offers a near-ideal combination of deep penetration
      and ultrahigh axial resolution for the imaging of biological tissue. The
      generation of SPDC light of adjustable bandwidth in the vicinity of 1064 nm, via
      the use of chirped-PPSLT structures, had not been previously achieved. To
      demonstrate the usefulness of this technique, we construct images for a hierarchy
      of samples of increasing complexity: a mirror, a nitrocellulose membrane, and a
      biological sample comprising onion-skin cells.

PMID- 19593357
TI  - Analysis of solving multimode-coupled equations and its improvement for modulated
      fiber Bragg gratings.
AB  - An efficient numerical method to solve multimode-coupled equations with two point
      boundary conditions is improved. Our method [Abrishamian et al., Opt. Fiber
      Technol.13, 32-38 (2007)] based on theoretical matrix integration of coupled
      differential equations and then solving the system of equations by use of initial
      or final conditions would be straightforward and thus beneficial in comparison
      with previously used fundamental matrix methods that depend strongly on the
      initial guess. However, we found that the new analysis depends on how accurately
      the integrals of the matrix element are calculated. For accuracy in the matrix
      integration it is required to divide the system of equations into a large number
      of subsections. Then, the reflectivity calculated is found to be comparable to
      experimental data reported so far. The present method is highly applicable for
      simulation of any type of fiber Bragg gratings modulated by long period gratings.

PMID- 19593358
TI  - Holey fiber design for single-polarization single-mode guidance.
AB  - We propose a holey fiber design to achieve single-polarization single-mode (SPSM)
      guidance. The photonic crystal fiber (PCF) has a triangular-lattice with
      elliptical airholes in the microstructured cladding and circular airholes in the
      core. The SPSM guidance can be obtained by designing the PCF structure such that
      the fundamental space-filling mode (FSM) of the core region is positioned between
      the indices of the two nondegenerate orthogonally polarized FSMs of the
      microstructured cladding.

PMID- 19593359
TI  - Scanning optical system with a constant speed of rays.
AB  - Our work deals with a theoretical analysis of an influence of a deviation from
      the sine condition of an optical system on the kinematics of aperture rays, which
      are transformed by this optical system. An exact formula for calculation of the
      value of the departure from the sine condition that has to be satisfied by an
      optical system to achieve a constant speed of transformed rays is derived.
      Approximate relations valid in the scope of the Seidel third-order aberrations
      theory are also derived and examples of optical systems that satisfy these
      conditions are presented. Obtained results are important for a design of scanning
      optical systems used, e.g., for distance measurements and laser systems for
      surface refinement of materials.

PMID- 19593360
TI  - Determination of velocity of self-mobile phytoplankton using a self-mixing thin
      slice solid-state laser.
AB  - We present an analysis of the shoulder-shaped power spectrum observed in the
      modulated laser output due to feedback light scattered from dynamic changes in
      self-mobile phytoplankton with flagella in seawater performed using a self-mixing
      laser Doppler vibrometry system. The power spectrum occasionally has shoulder
      shaped broad frequency components superimposed on a Lorentz-type spectrum. This
      reflects the translational motion of phytoplankton moving across the beam-focus
      area. The velocity of phytoplankton in the focus area can be obtained by applying
      a curve fitting procedure to the power spectrum. Moreover, the average velocity
      and the velocity distribution of phytoplankton can be determined from curve
      fitting of the long-term power spectrum.

PMID- 19593362
TI  - Predicting the distribution of spiral waves from cell properties in a
      developmental-path model of Dictyostelium pattern formation.
AB  - The slime mold Dictyostelium discoideum is one of the model systems of biological
      pattern formation. One of the most successful answers to the challenge of
      establishing a spiral wave pattern in a colony of homogeneously distributed D.
      discoideum cells has been the suggestion of a developmental path the cells follow
      (Lauzeral and coworkers). This is a well-defined change in properties each cell
      undergoes on a longer time scale than the typical dynamics of the cell. Here we
      show that this concept leads to an inhomogeneous and systematic spatial
      distribution of spiral waves, which can be predicted from the distribution of
      cells on the developmental path. We propose specific experiments for checking
      whether such systematics are also found in data and thus, indirectly, provide
      evidence of a developmental path.

PMID- 19593361
TI  - Membrane-anchored HIV-1 N-heptad repeat peptides are highly potent cell fusion
      inhibitors via an altered mode of action.
AB  - Peptide inhibitors derived from HIV-gp41 envelope protein play a pivotal role in
      deciphering the molecular mechanism of HIV-cell fusion. According to accepted
      models, N-heptad repeat (NHR) peptides can bind two targets in an intermediate
      fusion conformation, thereby inhibiting progression of the fusion process. In
      both cases the orientation towards the endogenous intermediate conformation
      should be important. To test this, we anchored NHR to the cell membrane by
      conjugating fatty acids with increasing lengths to the N- or C-terminus of N36,
      as well as to two known N36 mutants; one that cannot bind C-heptad repeat (CHR)
      but can bind NHR (N36 MUTe,g), and the second cannot bind to either NHR or CHR
      (N36 MUTa,d). Importantly, the IC(50) increased up to 100-fold in a lipopeptide
      dependent manner. However, no preferred directionality was observed for the wild
      type derived lipopeptides, suggesting a planar orientation of the peptides as
      well as the endogenous NHR region on the cell membrane. Furthermore, based on:
      (i) specialized analysis of the inhibition curves, (ii) the finding that N36
      conjugates reside more on the target cells that occupy the receptors, and (iii)
      the finding that N36 MUTe,g acts as a monomer both in its soluble form and when
      anchored to the cell membrane, we suggest that anchoring N36 to the cell changes
      the inhibitory mode from a trimer which can target both the endogenous NHR and
      CHR regions, to mainly monomeric lipopetides that target primarily the internal
      NHR. Besides shedding light on the mode of action of HIV-cell fusion, the
      similarity between functional regions in the envelopes of other viruses suggests
      a new approach for developing potent HIV-1 inhibitors.

PMID- 19593363
TI  - An experimental and computational study of the effect of ActA polarity on the
      speed of Listeria monocytogenes actin-based motility.
AB  - Listeria monocytogenes is a pathogenic bacterium that moves within infected cells
      and spreads directly between cells by harnessing the cell's dendritic actin
      machinery. This motility is dependent on expression of a single bacterial surface
      protein, ActA, a constitutively active Arp2,3 activator, and has been widely
      studied as a biochemical and biophysical model system for actin-based motility.
      Dendritic actin network dynamics are important for cell processes including
      eukaryotic cell motility, cytokinesis, and endocytosis. Here we experimentally
      altered the degree of ActA polarity on a population of bacteria and made use of
      an ActA-RFP fusion to determine the relationship between ActA distribution and
      speed of bacterial motion. We found a positive linear relationship for both ActA
      intensity and polarity with speed. We explored the underlying mechanisms of this
      dependence with two distinctly different quantitative models: a detailed agent
      based model in which each actin filament and branched network is explicitly
      simulated, and a three-state continuum model that describes a simplified
      relationship between bacterial speed and barbed-end actin populations. In silico
      bacterial motility required a cooperative restraining mechanism to reconstitute
      our observed speed-polarity relationship, suggesting that kinetic friction
      between actin filaments and the bacterial surface, a restraining force previously
      neglected in motility models, is important in determining the effect of ActA
      polarity on bacterial motility. The continuum model was less restrictive,
      requiring only a filament number-dependent restraining mechanism to reproduce our
      experimental observations. However, seemingly rational assumptions in the
      continuum model, e.g. an average propulsive force per filament, were invalidated
      by further analysis with the agent-based model. We found that the average
      contribution to motility from side-interacting filaments was actually a function
      of the ActA distribution. This ActA-dependence would be difficult to intuit but
      emerges naturally from the nanoscale interactions in the agent-based
      representation.

PMID- 19593365
TI  - Dynamic modeling of vaccinating behavior as a function of individual beliefs.
AB  - Individual perception of vaccine safety is an important factor in determining a
      person's adherence to a vaccination program and its consequences for disease
      control. This perception, or belief, about the safety of a given vaccine is not a
      static parameter but a variable subject to environmental influence. To complicate
      matters, perception of risk (or safety) does not correspond to actual risk. In
      this paper we propose a way to include the dynamics of such beliefs into a
      realistic epidemiological model, yielding a more complete depiction of the
      mechanisms underlying the unraveling of vaccination campaigns. The methodology
      proposed is based on Bayesian inference and can be extended to model more complex
      belief systems associated with decision models. We found the method is able to
      produce behaviors which approximate what has been observed in real vaccine and
      disease scare situations. The framework presented comprises a set of useful tools
      for an adequate quantitative representation of a common yet complex public-health
      issue. These tools include representation of beliefs as Bayesian probabilities,
      usage of logarithmic pooling to combine probability distributions representing
      opinions, and usage of natural conjugate priors to efficiently compute the
      Bayesian posterior. This approach allowed a comprehensive treatment of the
      uncertainty regarding vaccination behavior in a realistic epidemiological model.

PMID- 19593364
TI  - Analysis of the free-energy surface of proteins from reversible folding
      simulations.
AB  - Computer generated trajectories can, in principle, reveal the folding pathways of
      a protein at atomic resolution and possibly suggest general and simple rules for
      predicting the folded structure of a given sequence. While such reversible
      folding trajectories can only be determined ab initio using all-atom transferable
      force-fields for a few small proteins, they can be determined for a large number
      of proteins using coarse-grained and structure-based force-fields, in which a
      known folded structure is by construction the absolute energy and free-energy
      minimum. Here we use a model of the fast folding helical lambda-repressor protein
      to generate trajectories in which native and non-native states are in equilibrium
      and transitions are accurately sampled. Yet, representation of the free-energy
      surface, which underlies the thermodynamic and dynamic properties of the protein
      model, from such a trajectory remains a challenge. Projections over one or a
      small number of arbitrarily chosen progress variables often hide the most
      important features of such surfaces. The results unequivocally show that an
      unprojected representation of the free-energy surface provides important and
      unbiased information and allows a simple and meaningful description of many
      dimensional, heterogeneous trajectories, providing new insight into the possible
      mechanisms of fast-folding proteins.

PMID- 19593366
TI  - Rapid response of a marine mammal species to holocene climate and habitat change.
AB  - Environmental change drives demographic and evolutionary processes that determine
      diversity within and among species. Tracking these processes during periods of
      change reveals mechanisms for the establishment of populations and provides
      predictive data on response to potential future impacts, including those caused
      by anthropogenic climate change. Here we show how a highly mobile marine species
      responded to the gain and loss of new breeding habitat. Southern elephant seal,
      Mirounga leonina, remains were found along the Victoria Land Coast (VLC) in the
      Ross Sea, Antarctica, 2,500 km from the nearest extant breeding site on Macquarie
      Island (MQ). This habitat was released after retreat of the grounded ice sheet in
      the Ross Sea Embayment 7,500-8,000 cal YBP, and is within the range of modern
      foraging excursions from the MQ colony. Using ancient mtDNA and coalescent
      models, we tracked the population dynamics of the now extinct VLC colony and the
      connectivity between this and extant breeding sites. We found a clear expansion
      signal in the VLC population approximately 8,000 YBP, followed by directional
      migration away from VLC and the loss of diversity at approximately 1,000 YBP,
      when sea ice is thought to have expanded. Our data suggest that VLC seals came
      initially from MQ and that some returned there once the VLC habitat was lost,
      approximately 7,000 years later. We track the founder-extinction dynamics of a
      population from inception to extinction in the context of Holocene climate change
      and present evidence that an unexpectedly diverse, differentiated breeding
      population was founded from a distant source population soon after habitat became
      available.

PMID- 19593367
TI  - Distinct roles of non-canonical poly(A) polymerases in RNA metabolism.
AB  - Trf4p and Trf5p are non-canonical poly(A) polymerases and are part of the
      heteromeric protein complexes TRAMP4 and TRAMP5 that promote the degradation of
      aberrant and short-lived RNA substrates by interacting with the nuclear exosome.
      To assess the level of functional redundancy between the paralogous Trf4 and Trf5
      proteins and to investigate the role of the Trf4-dependent polyadenylation in
      vivo, we used DNA microarrays to compare gene expression of the wild-type yeast
      strain of S. cerevisiae with either that of trf4Delta or trf5Delta mutant strains
      or the trf4Delta mutant expressing the polyadenylation-defective Trf4(DADA)
      protein. We found little overlap between the sets of transcripts with altered
      expression in the trf4Delta or the trf5Delta mutants, suggesting that Trf4p and
      Trf5p target distinct groups of RNAs for degradation. Surprisingly, most RNAs the
      expression of which was altered by the trf4 deletion were restored to wild-type
      levels by overexpression of TRF4(DADA), showing that the polyadenylation activity
      of Trf4p is dispensable in vivo. Apart from previously reported Trf4p and Trf5p
      target RNAs, this analysis along with in vivo cross-linking and RNA
      immunopurification-chip experiments revealed that both the TRAMP4 and the TRAMP5
      complexes stimulate the degradation of spliced-out introns via a mechanism that
      is independent of the polyadenylation activity of Trf4p. In addition, we show
      that disruption of trf4 causes severe shortening of telomeres suggesting that
      TRF4 functions in the maintenance of telomere length. Finally, our study
      demonstrates that TRF4, the exosome, and TRF5 participate in antisense RNA
      mediated regulation of genes involved in phosphate metabolism. In conclusion, our
      results suggest that paralogous TRAMP complexes have distinct RNA selectivities
      with functional implications in RNA surveillance as well as other RNA-related
      processes. This indicates widespread and integrative functions of TRAMP complexes
      for the coordination of different gene expression regulatory processes.

PMID- 19593368
TI  - General rules for optimal codon choice.
AB  - Different synonymous codons are favored by natural selection for translation
      efficiency and accuracy in different organisms. The rules governing the
      identities of favored codons in different organisms remain obscure. In fact, it
      is not known whether such rules exist or whether favored codons are chosen
      randomly in evolution in a process akin to a series of frozen accidents. Here, we
      study this question by identifying for the first time the favored codons in 675
      bacteria, 52 archea, and 10 fungi. We use a number of tests to show that the
      identified codons are indeed likely to be favored and find that across all
      studied organisms the identity of favored codons tracks the GC content of the
      genomes. Once the effect of the genomic GC content on selectively favored codon
      choice is taken into account, additional universal amino acid specific rules
      governing the identity of favored codons become apparent. Our results provide for
      the first time a clear set of rules governing the evolution of selectively
      favored codon usage. Based on these results, we describe a putative scenario for
      how evolutionary shifts in the identity of selectively favored codons can occur
      without even temporary weakening of natural selection for codon bias.

PMID- 19593369
TI  - The ups and downs of mutation frequencies during aging can account for the Apert
      syndrome paternal age effect.
AB  - Apert syndrome is almost always caused by a spontaneous mutation of paternal
      origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene
      (FGFR2). The incidence of this disease increases with the age of the father
      (paternal age effect), and this increase is greater than what would be expected
      based on the greater number of germ-line divisions in older men. We use a highly
      sensitive PCR assay to measure the frequencies of the two causal mutations in the
      sperm of over 300 normal donors with a wide range of ages. The mutation
      frequencies increase with the age of the sperm donors, and this increase is
      consistent with the increase in the incidence rate. In both the sperm data and
      the birth data, the increase is non-monotonic. Further, after normalizing for
      age, the two Apert syndrome mutation frequencies are correlated within individual
      sperm donors. We consider a mathematical model for germ-line mutation which
      reproduces many of the attributes of the data. This model, with other evidence,
      suggests that part of the increase in both the sperm data and the birth data is
      due to selection for mutated premeiotic cells. It is likely that a number of
      other genetic diseases have similar features.

PMID- 19593370
TI  - Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding
      at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD).
AB  - Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy
      in which no mutation of pathogenic gene(s) has been identified. Instead, the
      disease is, in most cases, genetically linked to a contraction in the number of
      3.3 kb D4Z4 repeats on chromosome 4q. How contraction of the 4qter D4Z4 repeats
      causes muscular dystrophy is not understood. In addition, a smaller group of FSHD
      cases are not associated with D4Z4 repeat contraction (termed "phenotypic" FSHD),
      and their etiology remains undefined. We carried out chromatin
      immunoprecipitation analysis using D4Z4-specific PCR primers to examine the D4Z4
      chromatin structure in normal and patient cells as well as in small interfering
      RNA (siRNA)-treated cells. We found that SUV39H1-mediated H3K9 trimethylation at
      D4Z4 seen in normal cells is lost in FSHD. Furthermore, the loss of this histone
      modification occurs not only at the contracted 4q D4Z4 allele, but also at the
      genetically intact D4Z4 alleles on both chromosomes 4q and 10q, providing the
      first evidence that the genetic change (contraction) of one 4qD4Z4 allele spreads
      its effect to other genomic regions. Importantly, this epigenetic change was also
      observed in the phenotypic FSHD cases with no D4Z4 contraction, but not in other
      types of muscular dystrophies tested. We found that HP1gamma and cohesin are co
      recruited to D4Z4 in an H3K9me3-dependent and cell type-specific manner, which is
      disrupted in FSHD. The results indicate that cohesin plays an active role in HP1
      recruitment and is involved in cell type-specific D4Z4 chromatin regulation.
      Taken together, we identified the loss of both histone H3K9 trimethylation and
      HP1gamma/cohesin binding at D4Z4 to be a faithful marker for the FSHD phenotype.
      Based on these results, we propose a new model in which the epigenetic change
      initiated at 4q D4Z4 spreads its effect to other genomic regions, which
      compromises muscle-specific gene regulation leading to FSHD pathogenesis.

PMID- 19593371
TI  - Mre11-Rad50 promotes rapid repair of DNA damage in the polyploid archaeon
      Haloferax volcanii by restraining homologous recombination.
AB  - Polyploidy is frequent in nature and is a hallmark of cancer cells, but little is
      known about the strategy of DNA repair in polyploid organisms. We have studied
      DNA repair in the polyploid archaeon Haloferax volcanii, which contains up to 20
      genome copies. We have focused on the role of Mre11 and Rad50 proteins, which are
      found in all domains of life and which form a complex that binds to and
      coordinates the repair of DNA double-strand breaks (DSBs). Surprisingly, mre11
      rad50 mutants are more resistant to DNA damage than the wild-type. However, wild
      type cells recover faster from DNA damage, and pulsed-field gel electrophoresis
      shows that DNA double-strand breaks are repaired more slowly in mre11 rad50
      mutants. Using a plasmid repair assay, we show that wild-type and mre11 rad50
      cells use different strategies of DSB repair. In the wild-type, Mre11-Rad50
      appears to prevent the repair of DSBs by homologous recombination (HR), allowing
      microhomology-mediated end-joining to act as the primary repair pathway. However,
      genetic analysis of recombination-defective radA mutants suggests that DNA repair
      in wild-type cells ultimately requires HR, therefore Mre11-Rad50 merely delays
      this mode of repair. In polyploid organisms, DSB repair by HR is potentially
      hazardous, since each DNA end will have multiple partners. We show that in the
      polyploid archaeon H. volcanii the repair of DSBs by HR is restrained by Mre11
      Rad50. The unrestrained use of HR in mre11 rad50 mutants enhances cell survival
      but leads to slow recovery from DNA damage, presumably due to difficulties in the
      resolution of DNA repair intermediates. Our results suggest that recombination
      might be similarly repressed in other polyploid organisms and at repetitive
      sequences in haploid and diploid species.

PMID- 19593372
TI  - Bistable perception modeled as competing stochastic integrations at two levels.
AB  - We propose a novel explanation for bistable perception, namely, the collective
      dynamics of multiple neural populations that are individually meta-stable.
      Distributed representations of sensory input and of perceptual state build
      gradually through noise-driven transitions in these populations, until the
      competition between alternative representations is resolved by a threshold
      mechanism. The perpetual repetition of this collective race to threshold renders
      perception bistable. This collective dynamics - which is largely uncoupled from
      the time-scales that govern individual populations or neurons - explains many
      hitherto puzzling observations about bistable perception: the wide range of mean
      alternation rates exhibited by bistable phenomena, the consistent variability of
      successive dominance periods, and the stabilizing effect of past perceptual
      states. It also predicts a number of previously unsuspected relationships between
      observable quantities characterizing bistable perception. We conclude that
      bistable perception reflects the collective nature of neural decision making
      rather than properties of individual populations or neurons.

PMID- 19593373
TI  - Integrating sequencing technologies in personal genomics: optimal low cost
      reconstruction of structural variants.
AB  - The goal of human genome re-sequencing is obtaining an accurate assembly of an
      individual's genome. Recently, there has been great excitement in the development
      of many technologies for this (e.g. medium and short read sequencing from
      companies such as 454 and SOLiD, and high-density oligo-arrays from Affymetrix
      and NimbelGen), with even more expected to appear. The costs and sensitivities of
      these technologies differ considerably from each other. As an important goal of
      personal genomics is to reduce the cost of re-sequencing to an affordable point,
      it is worthwhile to consider optimally integrating technologies. Here, we build a
      simulation toolbox that will help us optimally combine different technologies for
      genome re-sequencing, especially in reconstructing large structural variants
      (SVs). SV reconstruction is considered the most challenging step in human genome
      re-sequencing. (It is sometimes even harder than de novo assembly of small
      genomes because of the duplications and repetitive sequences in the human
      genome.) To this end, we formulate canonical problems that are representative of
      issues in reconstruction and are of small enough scale to be computationally
      tractable and simulatable. Using semi-realistic simulations, we show how we can
      combine different technologies to optimally solve the assembly at low cost. With
      mapability maps, our simulations efficiently handle the inhomogeneous repeat
      containing structure of the human genome and the computational complexity of
      practical assembly algorithms. They quantitatively show how combining different
      read lengths is more cost-effective than using one length, how an optimal mixed
      sequencing strategy for reconstructing large novel SVs usually also gives
      accurate detection of SNPs/indels, how paired-end reads can improve
      reconstruction efficiency, and how adding in arrays is more efficient than just
      sequencing for disentangling some complex SVs. Our strategy should facilitate the
      sequencing of human genomes at maximum accuracy and low cost.

PMID- 19593374
TI  - Computational fragment-based binding site identification by ligand competitive
      saturation.
AB  - Fragment-based drug discovery using NMR and x-ray crystallographic methods has
      proven utility but also non-trivial time, materials, and labor costs. Current
      computational fragment-based approaches circumvent these issues but suffer from
      limited representations of protein flexibility and solvation effects, leading to
      difficulties with rigorous ranking of fragment affinities. To overcome these
      limitations we describe an explicit solvent all-atom molecular dynamics
      methodology (SILCS: Site Identification by Ligand Competitive Saturation) that
      uses small aliphatic and aromatic molecules plus water molecules to map the
      affinity pattern of a protein for hydrophobic groups, aromatic groups, hydrogen
      bond donors, and hydrogen bond acceptors. By simultaneously incorporating ligands
      representative of all these functionalities, the method is an in silico free
      energy-based competition assay that generates three-dimensional probability maps
      of fragment binding (FragMaps) indicating favorable fragment:protein
      interactions. Applied to the two-fold symmetric oncoprotein BCL-6, the SILCS
      method yields two-fold symmetric FragMaps that recapitulate the crystallographic
      binding modes of the SMRT and BCOR peptides. These FragMaps account both for
      important sequence and structure differences in the C-terminal halves of the two
      peptides and also the high mobility of the BCL-6 His116 sidechain in the peptide
      binding groove. Such SILCS FragMaps can be used to qualitatively inform the
      design of small-molecule inhibitors or as scoring grids for high-throughput in
      silico docking that incorporate both an atomic-level description of solvation and
      protein flexibility.

PMID- 19593375
TI  - A Multiparent Advanced Generation Inter-Cross to fine-map quantitative traits in
      Arabidopsis thaliana.
AB  - Identifying natural allelic variation that underlies quantitative trait variation
      remains a fundamental problem in genetics. Most studies have employed either
      simple synthetic populations with restricted allelic variation or performed
      association mapping on a sample of naturally occurring haplotypes. Both of these
      approaches have some limitations, therefore alternative resources for the genetic
      dissection of complex traits continue to be sought. Here we describe one such
      alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This
      approach is expected to improve the precision with which QTL can be mapped,
      improving the outlook for QTL cloning. Here, we present the first panel of MAGIC
      lines developed: a set of 527 recombinant inbred lines (RILs) descended from a
      heterogeneous stock of 19 intermated accessions of the plant Arabidopsis
      thaliana. These lines and the 19 founders were genotyped with 1,260 single
      nucleotide polymorphisms and phenotyped for development-related traits.
      Analytical methods were developed to fine-map quantitative trait loci (QTL) in
      the MAGIC lines by reconstructing the genome of each line as a mosaic of the
      founders. We show by simulation that QTL explaining 10% of the phenotypic
      variance will be detected in most situations with an average mapping error of
      about 300 kb, and that if the number of lines were doubled the mapping error
      would be under 200 kb. We also show how the power to detect a QTL and the mapping
      accuracy vary, depending on QTL location. We demonstrate the utility of this new
      mapping population by mapping several known QTL with high precision and by
      finding novel QTL for germination data and bolting time. Our results provide
      strong support for similar ongoing efforts to produce MAGIC lines in other
      organisms.

PMID- 19593376
TI  - The Kunitz-like modulatory protein haemangin is vital for hard tick blood-feeding
      success.
AB  - Ticks are serious haematophagus arthropod pests and are only second to mosquitoes
      as vectors of diseases of humans and animals. The salivary glands of the slower
      feeding hard ticks such as Haemaphysalis longicornis are a rich source of
      bioactive molecules and are critical to their biologic success, yet distinct
      molecules that help prolong parasitism on robust mammalian hosts and achieve
      blood-meals remain unidentified. Here, we report on the molecular and biochemical
      features and precise functions of a novel Kunitz inhibitor from H. longicornis
      salivary glands, termed Haemangin, in the modulation of angiogenesis and in
      persistent blood-feeding. Haemangin was shown to disrupt angiogenesis and wound
      healing via inhibition of vascular endothelial cell proliferation and induction
      of apoptosis. Further, this compound potently inactivated trypsin, chymotrypsin,
      and plasmin, indicating its antiproteolytic potential on angiogenic cascades.
      Analysis of Haemangin-specific gene expression kinetics at different blood
      feeding stages of adult ticks revealed a dramatic up-regulation prior to complete
      feeding, which appears to be functionally linked to the acquisition of blood
      meals. Notably, disruption of Haemangin-specific mRNA by a reverse genetic tool
      significantly diminished engorgement of adult H. longicornis, while the knock
      down ticks failed to impair angiogenesis in vivo. To our knowledge, we have
      provided the first insights into transcriptional responses of human microvascular
      endothelial cells to Haemangin. DNA microarray data revealed that Haemangin
      altered the expression of 3,267 genes, including those of angiogenic
      significance, further substantiating the antiangiogenic function of Haemangin. We
      establish the vital roles of Haemangin in the hard tick blood-feeding process.
      Moreover, our results provide novel insights into the blood-feeding strategies
      that enable hard ticks to persistently feed and ensure full blood-meals through
      the modulation of angiogenesis and wound healing processes.

PMID- 19593377
TI  - Genome-scale identification of Legionella pneumophila effectors using a machine
      learning approach.
AB  - A large number of highly pathogenic bacteria utilize secretion systems to
      translocate effector proteins into host cells. Using these effectors, the
      bacteria subvert host cell processes during infection. Legionella pneumophila
      translocates effectors via the Icm/Dot type-IV secretion system and to date,
      approximately 100 effectors have been identified by various experimental and
      computational techniques. Effector identification is a critical first step
      towards the understanding of the pathogenesis system in L. pneumophila as well as
      in other bacterial pathogens. Here, we formulate the task of effector
      identification as a classification problem: each L. pneumophila open reading
      frame (ORF) was classified as either effector or not. We computationally defined
      a set of features that best distinguish effectors from non-effectors. These
      features cover a wide range of characteristics including taxonomical dispersion,
      regulatory data, genomic organization, similarity to eukaryotic proteomes and
      more. Machine learning algorithms utilizing these features were then applied to
      classify all the ORFs within the L. pneumophila genome. Using this approach we
      were able to predict and experimentally validate 40 new effectors, reaching a
      success rate of above 90%. Increasing the number of validated effectors to around
      140, we were able to gain novel insights into their characteristics. Effectors
      were found to have low G+C content, supporting the hypothesis that a large number
      of effectors originate via horizontal gene transfer, probably from their
      protozoan host. In addition, effectors were found to cluster in specific genomic
      regions. Finally, we were able to provide a novel description of the C-terminal
      translocation signal required for effector translocation by the Icm/Dot secretion
      system. To conclude, we have discovered 40 novel L. pneumophila effectors,
      predicted over a hundred additional highly probable effectors, and shown the
      applicability of machine learning algorithms for the identification and
      characterization of bacterial pathogenesis determinants.

PMID- 19593378
TI  - Relating neuronal firing patterns to functional differentiation of cerebral
      cortex.
AB  - It has been empirically established that the cerebral cortical areas defined by
      Brodmann one hundred years ago solely on the basis of cellular organization are
      closely correlated to their function, such as sensation, association, and motion.
      Cytoarchitectonically distinct cortical areas have different densities and types
      of neurons. Thus, signaling patterns may also vary among cytoarchitectonically
      unique cortical areas. To examine how neuronal signaling patterns are related to
      innate cortical functions, we detected intrinsic features of cortical firing by
      devising a metric that efficiently isolates non-Poisson irregular
      characteristics, independent of spike rate fluctuations that are caused
      extrinsically by ever-changing behavioral conditions. Using the new metric, we
      analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by
      eight independent neurophysiological laboratories. Analysis of firing-pattern
      dissimilarities across cortical areas revealed a gradient of firing regularity
      that corresponded closely to the functional category of the cortical area;
      neuronal spiking patterns are regular in motor areas, random in the visual areas,
      and bursty in the prefrontal area. Thus, signaling patterns may play an important
      role in function-specific cerebral cortical computation.

PMID- 19593379
TI  - Structure and inhibition of the SARS coronavirus envelope protein ion channel.
AB  - The envelope (E) protein from coronaviruses is a small polypeptide that contains
      at least one alpha-helical transmembrane domain. Absence, or inactivation, of E
      protein results in attenuated viruses, due to alterations in either virion
      morphology or tropism. Apart from its morphogenetic properties, protein E has
      been reported to have membrane permeabilizing activity. Further, the drug
      hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel
      activity of some synthetic coronavirus E proteins, and also viral replication. We
      have previously shown for the coronavirus species responsible for severe acute
      respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM)
      forms pentameric alpha-helical bundles that are likely responsible for the
      observed channel activity. Herein, using solution NMR in
      dodecylphosphatidylcholine micelles and energy minimization, we have obtained a
      model of this channel which features regular alpha-helices that form a pentameric
      left-handed parallel bundle. The drug HMA was found to bind inside the lumen of
      the channel, at both the C-terminal and the N-terminal openings, and, in contrast
      to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E
      displayed channel activity when transiently expressed in human embryonic kidney
      293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was
      significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The
      channel structure presented herein provides a possible rationale for inhibition,
      and a platform for future structure-based drug design of this potential
      pharmacological target.

PMID- 19593380
TI  - Movement timing and invariance arise from several geometries.
AB  - Human movements show several prominent features; movement duration is nearly
      independent of movement size (the isochrony principle), instantaneous speed
      depends on movement curvature (captured by the 2/3 power law), and complex
      movements are composed of simpler elements (movement compositionality). No
      existing theory can successfully account for all of these features, and the
      nature of the underlying motion primitives is still unknown. Also unknown is how
      the brain selects movement duration. Here we present a new theory of movement
      timing based on geometrical invariance. We propose that movement duration and
      compositionality arise from cooperation among Euclidian, equi-affine and full
      affine geometries. Each geometry posses a canonical measure of distance along
      curves, an invariant arc-length parameter. We suggest that for continuous
      movements, the actual movement duration reflects a particular tensorial mixture
      of these canonical parameters. Near geometrical singularities, specific
      combinations are selected to compensate for time expansion or compression in
      individual parameters. The theory was mathematically formulated using Cartan's
      moving frame method. Its predictions were tested on three data sets: drawings of
      elliptical curves, locomotion and drawing trajectories of complex figural forms
      (cloverleaves, lemniscates and limacons, with varying ratios between the sizes of
      the large versus the small loops). Our theory accounted well for the kinematic
      and temporal features of these movements, in most cases better than the
      constrained Minimum Jerk model, even when taking into account the number of
      estimated free parameters. During both drawing and locomotion equi-affine
      geometry was the most dominant geometry, with affine geometry second most
      important during drawing; Euclidian geometry was second most important during
      locomotion. We further discuss the implications of this theory: the origin of the
      dominance of equi-affine geometry, the possibility that the brain uses different
      mixtures of these geometries to encode movement duration and speed, and the
      ontogeny of such representations.

PMID- 19593381
TI  - DNA structure modulates the oligomerization properties of the AAV initiator
      protein Rep68.
AB  - Rep68 is a multifunctional protein of the adeno-associated virus (AAV), a
      parvovirus that is mostly known for its promise as a gene therapy vector. In
      addition to its role as initiator in viral DNA replication, Rep68 is essential
      for site-specific integration of the AAV genome into human chromosome 19. Rep68
      is a member of the superfamily 3 (SF3) helicases, along with the well-studied
      initiator proteins simian virus 40 large T antigen (SV40-LTag) and bovine
      papillomavirus (BPV) E1. Structurally, SF3 helicases share two domains, a DNA
      origin interaction domain (OID) and an AAA(+) motor domain. The AAA(+) motor
      domain is also a structural feature of cellular initiators and it functions as a
      platform for initiator oligomerization. Here, we studied Rep68 oligomerization in
      vitro in the presence of different DNA substrates using a variety of biophysical
      techniques and cryo-EM. We found that a dsDNA region of the AAV origin promotes
      the formation of a complex containing five Rep68 subunits. Interestingly, non
      specific ssDNA promotes the formation of a double-ring Rep68, a known structure
      formed by the LTag and E1 initiator proteins. The Rep68 ring symmetry is 8-fold,
      thus differing from the hexameric rings formed by the other SF3 helicases.
      However, similiar to LTag and E1, Rep68 rings are oriented head-to-head,
      suggesting that DNA unwinding by the complex proceeds bidirectionally. This novel
      Rep68 quaternary structure requires both the DNA binding and AAA(+) domains,
      indicating cooperativity between these regions during oligomerization in vitro.
      Our study clearly demonstrates that Rep68 can oligomerize through two distinct
      oligomerization pathways, which depend on both the DNA structure and
      cooperativity of Rep68 domains. These findings provide insight into the dynamics
      and oligomeric adaptability of Rep68 and serve as a step towards understanding
      the role of this multifunctional protein during AAV DNA replication and site
      specific integration.

PMID- 19593382
TI  - Actin dynamics regulate multiple endosomal steps during Kaposi's sarcoma
      associated herpesvirus entry and trafficking in endothelial cells.
AB  - The role of actin dynamics in clathrin-mediated endocytosis in mammalian cells is
      unclear. In this study, we define the role of actin cytoskeleton in Kaposi's
      sarcoma-associated herpesvirus (KSHV) entry and trafficking in endothelial cells
      using an immunofluorescence-based assay to visualize viral capsids and the
      associated cellular components. In contrast to infectivity or reporter assays,
      this method does not rely on the expression of any viral and reporter genes, but
      instead directly tracks the accumulation of individual viral particles at the
      nuclear membrane as an indicator of successful viral entry and trafficking in
      cells. Inhibitors of endosomal acidification reduced both the percentage of
      nuclei with viral particles and the total number of viral particles docking at
      the perinuclear region, indicating endocytosis, rather than plasma membrane
      fusion, as the primary route for KSHV entry into endothelial cells. Accordingly,
      a viral envelope protein was only detected on internalized KSHV particles at the
      early but not late stage of infection. Inhibitors of clathrin- but not
      caveolae/lipid raft-mediated endocytosis blocked KSHV entry, indicating that
      clathrin-mediated endocytosis is the major route of KSHV entry into endothelial
      cells. KSHV particles were colocalized not only with markers of early and
      recycling endosomes, and lysosomes, but also with actin filaments at the early
      time points of infection. Consistent with these observations, transferrin, which
      enters cells by clathrin-mediated endocytosis, was found to be associated with
      actin filaments together with early and recycling endosomes, and to a lesser
      degree, with late endosomes and lysosomes. KSHV infection induced dynamic actin
      cytoskeleton rearrangements. Disruption of the actin cytoskeleton and inhibition
      of regulators of actin nucleation such as Rho GTPases and Arp2/3 complex
      profoundly blocked KSHV entry and trafficking. Together, these results indicate
      an important role for actin dynamics in the internalization and endosomal
      sorting/trafficking of KSHV and clathrin-mediated endocytosis in endothelial
      cells.

PMID- 19593383
TI  - Defects in tRNA modification associated with neurological and developmental
      dysfunctions in Caenorhabditis elegans elongator mutants.
AB  - Elongator is a six subunit protein complex, conserved from yeast to humans.
      Mutations in the human Elongator homologue, hELP1, are associated with the
      neurological disease familial dysautonomia. However, how Elongator functions in
      metazoans, and how the human mutations affect neural functions is incompletely
      understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3,
      components of the Elongator complex, are required for the formation of the 5
      carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA.
      The lack of these modifications leads to defects in translation in C. elegans.
      ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of
      chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene
      inactivation causes a defect in this process, associated with a
      posttranscriptional reduction of neuropeptide and a decreased accumulation of
      acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic
      lethal together with those in tuc-1, which is required for thiolation of tRNAs
      having the 5'methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1
      double mutants display developmental defects. Our results suggest that, by its
      effect on tRNA modification, Elongator promotes both neural function and
      development.

PMID- 19593384
TI  - Dissociable perceptual effects of visual adaptation.
AB  - Neurons in the visual cortex are responsive to the presentation of oriented and
      curved line segments, which are thought to act as primitives for the visual
      processing of shapes and objects. Prolonged adaptation to such stimuli gives rise
      to two related perceptual effects: a slow change in the appearance of the
      adapting stimulus (perceptual drift), and the distortion of subsequently
      presented test stimuli (adaptational aftereffects). Here we used a psychophysical
      nulling technique to dissociate and quantify these two classical observations in
      order to examine their underlying mechanisms and their relationship to one
      another. In agreement with previous work, we found that during adaptation
      horizontal and vertical straight lines serve as attractors for perceived
      orientation and curvature. However, the rate of perceptual drift for different
      stimuli was not predictive of the corresponding aftereffect magnitudes,
      indicating that the two perceptual effects are governed by distinct neural
      processes. Finally, the rate of perceptual drift for curved line segments did not
      depend on the spatial scale of the stimulus, suggesting that its mechanisms lie
      outside strictly retinotopic processing stages. These findings provide new
      evidence that the visual system relies on statistically salient intrinsic
      reference stimuli for the processing of visual patterns, and point to perceptual
      drift as an experimental window for studying the mechanisms of visual perception.

PMID- 19593386
TI  - Wnt signaling is regulated by endoplasmic reticulum retention.
AB  - Precise regulation of Wnt signaling is important in many contexts, as in
      development of the vertebrate forebrain, where excessive or ectopic Wnt signaling
      leads to severe brain defects. Mutation of the widely expressed oto gene causes
      loss of the anterior forebrain during mouse embryogenesis. Here we report that
      oto is the mouse ortholog of the gpi deacylase gene pgap1, and that the
      endoplasmic reticulum (ER)-resident Oto protein has a novel and deacylase
      independent function during Wnt maturation. Oto increases the hydrophobicities of
      Wnt3a and Wnt1 by promoting the addition of glycophosphatidylinositol (gpi)-like
      anchors to these Wnts, which results in their retention in the ER. We also report
      that oto-deficient embryos exhibit prematurely robust Wnt activity in the Wnt1
      domain of the early neural plate. We examine the effect of low oto expression on
      Wnt1 in vitro by knocking down endogenous oto expression in 293 and M14 melanoma
      cells using shRNA. Knockdown of oto results in increased Wnt1 secretion which is
      correlated with greatly enhanced canonical Wnt activity. These data indicate that
      oto deficiency increases Wnt signaling in vivo and in vitro. Finally, we address
      the mechanism of Oto-mediated Wnt retention under oto-abundant conditions, by
      cotransfecting Wnt1 with gpi-specific phospholipase D (GPI-PLD). The presence of
      GPI-PLD in the secretory pathway results in increased secretion of soluble Wnt1,
      suggesting that the gpi-like anchor lipids on Wnt1 mediate its retention in the
      ER. These data now provide a mechanistic framework for understanding the
      forebrain defects in oto mice, and support a role for Oto-mediated Wnt regulation
      during early brain development. Our work highlights a critical role for ER
      retention in regulating Wnt signaling in the mouse embryo, and gives insight into
      the notoriously inefficient secretion of Wnts.

PMID- 19593387
TI  - Reduction of canine plasminogen leads to an expanded molecule which precipitates.
AB  - Canine plasminogen is made up of seven domains. In each domain there are several
      cysteines that are linked by disulfide bonds. Reduction of a limited number of
      the cystines destabilizes the protein such that it precipitates. The bond or
      bonds that are broken provide about 14 kcal of stabilization energy. Circular
      dichroism and dynamic light scattering indicate that there is probably an
      intermediate that is formed prior to precipitation and that the intermediate is
      somewhat larger than the compact form of plasminogen.

PMID- 19593385
TI  - Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway.
AB  - BACKGROUND: The signaling pathways imposing hormonal control over adipocyte
      differentiation are poorly understood. While insulin and Akt signaling have been
      found previously to be essential for adipogenesis, the relative importance of
      their many downstream branches have not been defined. One direct substrate that
      is inhibited by Akt-mediated phosphorylation is the tuberous sclerosis complex 2
      (TSC2) protein, which associates with TSC1 and acts as a critical negative
      regulator of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). Loss of
      function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and,
      through mTORC1-dependent feedback mechanisms and loss of mTORC2 activity, leads
      to a concomitant block of Akt signaling to its other downstream targets.
      METHODOLOGY/PRINCIPAL FINDINGS: We find that, despite severe insulin resistance
      and the absence of Akt signaling, TSC2-deficient mouse embryo fibroblasts and 3T3
      L1 pre-adipocytes display enhanced adipocyte differentiation that is dependent on
      the elevated mTORC1 activity in these cells. Activation of mTORC1 causes a robust
      increase in the mRNA and protein expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), which is the master transcriptional regulator of
      adipocyte differentiation. In examining the requirements for different Akt
      mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking
      all five previously identified Akt sites fully block insulin-stimulated mTORC1
      signaling in reconstituted Tsc2 null cells, and this mutant also inhibits
      adipogenesis. Finally, renal angiomyolipomas from patients with tuberous
      sclerosis complex contain both adipose and smooth muscle-like components with
      activated mTORC1 signaling and elevated PPARgamma expression.
      CONCLUSIONS/SIGNIFICANCE: This study demonstrates that activation of mTORC1
      signaling is a critical step in adipocyte differentiation and identifies TSC2 as
      a primary target of Akt driving this process. Therefore, the TSC1-TSC2 complex
      regulates the differentiation of mesenchymal cell lineages, at least in part,
      through its control of mTORC1 activity and PPARgamma expression.

PMID- 19593388
TI  - CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of
      neurocognitive dysfunction.
AB  - BACKGROUND: The linkages between neuroinflammation and Alzheimer's disease (AD)
      pathogenesis are well established. What is not, however, is how specific immune
      pathways and proteins affect the disease. To this end, we previously demonstrated
      that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse
      amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a
      Swedish beta-amyloid (Abeta) precursor protein mutant. METHODOLOGY/PRINCIPAL
      FINDINGS: We now report that CCL2 transgene expression accelerates deficits in
      spatial and working memory and hippocampal synaptic transmission in beta-amyloid
      precursor protein (APP) mice as early as 2-3 months of age. This is followed by
      increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2
      does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha
      directly facilitated Abeta uptake, intracellular Abeta oligomerization, and
      protein secretion. CONCLUSIONS/SIGNIFICANCE: We posit that CCL2 facilitates Abeta
      oligomer formation in microglia and propose that such events accelerate memory
      dysfunction by affecting Abeta seeding in the brain.

PMID- 19593390
TI  - An Operationally Simple and Efficient Synthesis of Orthogonally Protected L-threo
      beta-Hydroxyasparagine.
AB  - A synthesis of orthogonally protected L-threo-beta-hydroxyasparagine from L
      aspartic acid is reported. Iodocyclization of 3-benzoylaminoaspartic acid
      provided an intermediate oxazoline dicarboxylate that was efficiently hydrolyzed
      to L-threo-beta-hydroxyaspartic acid. The synthetic route for conversion of the
      free beta-hydroxy-alpha-amino acid into the target compound is highly efficient
      and amenable to preparation various orthogonally protected asparagine
      derivatives, on a multiple gram scale.

PMID- 19593389
TI  - Heterogeneity in macrophage phagocytosis of Staphylococcus aureus strains: high
      throughput scanning cytometry-based analysis.
AB  - Alveolar macrophages (AMs) can phagocytose unopsonized pathogens such as S.
      aureus via innate immune receptors, such as scavenger receptors (SRs).
      Cytoskeletal events and signaling pathways involved in phagocytosis of
      unopsonized bacteria likely govern the fate of ingested pathogens, but are poorly
      characterized. We have developed a high-throughput scanning cytometry-based assay
      to quantify phagocytosis of S. aureus by adherent human blood-derived AM-like
      macrophages in a 96-well microplate format. Differential fluorescent labeling of
      internalized vs. bound bacteria or beads allowed automated image analysis of
      collapsed confocal stack images acquired by scanning cytometry, and
      quantification of total particles bound and percent of particles internalized. We
      compared the effects of the classic SR blocker polyinosinic acid, the
      cytoskeletal inhibitors cytochalasin D and nocodazole, and the signaling
      inhibitors staurosporine, Go 6976, JNK Inhibitor I and KN-93, on phagocytosis of
      a panel of live unopsonized S. aureus strains, (Wood, Seattle 1945 (ATCC 25923),
      and RN6390), as well as a commercial killed Wood strain, heat-killed Wood strain
      and latex beads. Our results revealed failure of the SR inhibitor polyinosinic
      acid to block binding of any live S. aureus strains, suggesting that SR-mediated
      uptake of a commercial killed fluorescent bacterial particle does not accurately
      model interaction with viable bacteria. We also observed heterogeneity in the
      effects of cytoskeletal and signaling inhibitors on internalization of different
      S. aureus strains. The data suggest that uptake of unopsonized live S. aureus by
      human macrophages is not mediated by SRs, and that the cellular mechanical and
      signaling processes that mediate S. aureus phagocytosis vary. The findings also
      demonstrate the potential utility of high-throughput scanning cytometry
      techniques to study phagocytosis of S. aureus and other organisms in greater
      detail.

PMID- 19593391
TI  - Bioethical concerns are global, bioethics is Western.
AB  - Modern bioethics was born in the West and thus reflects, not surprisingly, the
      traditions of Western moral philosophy and political and social theory. When the
      work of bioethics was confined to the West, this background of socio-political
      theory and moral tradition posed few problems, but as bioethics has moved into
      other cultures - inside and outside of the Western world - it has become an agent
      of moral imperialism. We describe the moral imperialism of bioethics, discuss its
      dangers, and suggest that global bioethics will succeed only to the extent that
      it is local.

PMID- 19593392
TI  - A Study of Probabilistic Models for Characterizing Human Heart Beat Dynamics in
      Autonomic Blockade Control.
AB  - In this paper, we compare and validate different probabilistic models of human
      heart beat intervals for assessment of the electrocardiogram data recorded with
      varying conditions in posture and pharmacological autonomic blockade. The models
      are validated using the adaptive point process filtering paradigm and Kolmogorov
      Smirnov test. The inverse Gaussian model was found to achieve the overall best
      performance in the analysis of autonomic control. We further improve the model by
      incorporating the respiratory covariate measurements and present dynamic
      respiratory sinus arrhythmia (RSA) analysis. Our results suggest the
      instantaneous RSA gain computed from our proposed model as a potential index of
      vagal control dynamics.

PMID- 19593393
TI  - Theta-Modulated Input Reduces Intrinsic Gamma Oscillations in a Hippocampal
      Model.
AB  - Introducing theta-modulated input into a minimal model of the CA3 region of the
      hippocampus has significant effects on gamma oscillations. In the absence of
      theta-modulated input, the gamma oscillations are robust across a range of
      parameters. Introducing theta-modulated input weakens the gamma oscillations to a
      power more consistent with power spectra acquired from laboratory animals. With
      these changes, simulations of the hippocampal model are able to reproduce
      hippocampal power spectra measured in awake mice.

PMID- 19593394
TI  - The return of the repressed: Abandoned parses facilitate syntactic reanalysis.
AB  - Two eye movement experiments examined effects on syntactic reanalysis when the
      correct analysis was briefly entertained at an earlier point in the sentence. In
      Experiment 1, participants read sentences containing a noun phrase
      coordination/clausal coordination ambiguity, while in Experiment 2 they read
      sentences containing a subordinate clause object/main clause subject ambiguity.
      The critical conditions were designed to induce readers to construct the
      ultimately correct analysis just prior to being garden-pathed by the incorrect
      analysis. In both experiments, the earliest measures of the garden path effect
      were not modulated by this manipulation. However, there was significantly less
      regressive re-reading of the sentence in those conditions in which the correct
      analysis was likely to have been constructed, then abandoned, at an earlier
      point. These results suggest that a syntactic analysis that is abandoned in the
      course of processing a sentence is not lost altogether, and can be re-activated
      or retrieved from memory. Implications for models of initial syntactic analysis
      and reanalysis are discussed.

PMID- 19593395
TI  - Electronic Structure of the d Bent-metallocene Cp(2)VCl(2): A Photoelectron and
      Density Functional Study.
AB  - The Cp(2)VCl(2) molecule is a prototype for bent metallocene complexes with a
      single electron in the metal d shell, but experimental measure of the binding
      energy of the d electron by photoelectron spectroscopy eluded early attempts due
      to apparent decomposition in the spectrometer to Cp(2)VCl. With improved
      instrumentation, the amount of decomposition is reduced and subtraction of
      ionization intensity due to Cp(2)VCl from the Cp(2)VCl(2)/Cp(2)VCl mixed spectrum
      yields the Cp(2)VCl(2) spectrum exclusively. The measured ionization energies
      provide well-defined benchmarks for electronic structure calculations. Density
      functional calculations support the spectral interpretations and agree well with
      the ionization energy of the d(1) electron and the energies of the higher
      positive ion states of Cp(2)VCl(2). The calculations also account well for the
      trends to the other Group V bent metallocene dichlorides Cp(2)NbCl(2) and
      Cp(2)TaCl(2). The first ionization energy of Cp(2)VCl(2) is considerably greater
      than the first ionization energies of the second- and third-row transition metal
      analogues.

PMID- 19593397
TI  - Health consequences of aircraft noise.
AB  - INTRODUCTION: The ever-increasing level of air traffic means that any medical
      evaluation of its effects must be based on recent data. METHODS: Selective
      literature review of epidemiological studies from 2000 to 2007 regarding the
      illnesses, annoyance, and learning disorders resulting from aircraft noise.
      RESULTS: In residential areas, outdoor aircraft noise-induced equivalent noise
      levels of 60 dB(A) in the daytime and 45 dB(A) at night are associated with an
      increased incidence of hypertension. There is a dose-response relationship
      between aircraft noise and the occurrence of arterial hypertension. The
      prescription frequency of blood pressure-lowering medications is associated dose
      dependently with aircraft noise from a level of about 45 dB(A). Around 25% of the
      population are greatly annoyed by exposure to noise of 55 dB(A) during the
      daytime. Exposure to 50 dB(A) in the daytime (outside) is associated with
      relevant learning difficulties in schoolchildren. DISCUSSION: Based on recent
      epidemiological studies, outdoor noise limits of 60 dB(A) in the daytime and 50
      dB(A) at night can be recommended on grounds of health protection. Hence, maximum
      values of 55 dB(A) for the day and 45 dB(A) for the night should be aimed for in
      order to protect the more sensitive segments of the population such as children,
      the elderly, and the chronically ill. These values are 5 to 10 dB(A) lower than
      those specified by the German federal law on aircraft noise and in the report
      "synopsis" commissioned by the company that runs Frankfurt airport (Fraport).

PMID- 19593399
TI  - Requirements too high.

PMID- 19593398
TI  - Evidence based guidelines.

PMID- 19593396
TI  - Imaging studies for the early detection of breast cancer.
AB  - INTRODUCTION: The effectiveness of mammographic screening has been proven at
      evidence level 1A. Mammography offers the best ratio of benefits to side effects
      of any screening method tested to date. In this literature review, we ask whether
      early detection might be improved still further by combining mammography with
      other imaging modalities. METHODS: The authors performed a selective literature
      search for combined key words in the Medline and Cochrane Library databases from
      1/2000 to 11/2007, screened all titles, and evaluated the full text of all
      original articles. We selected articles for further analysis according to
      systematic criteria (minimum numbers, avoidance of overlap) and also considered
      published guidelines. RESULTS: No screening studies of comparable size to those
      for mammography are available for ultrasound or MRI. Smaller studies have
      indicated that the use of these two modalities might lead to the detection of
      additional cancers in selected subgroups. For mass screening an increase in the
      detection rate of 10% to 15% might become possible. This increase would probably
      be associated with a tripling of the breast biopsy rate, compared to mammography
      alone. The number of indeterminate cases in which short-term follow-up (i.e., at
      6 months) would be recommended would increase roughly tenfold with MRI, and to an
      unknown extent with ultrasound. The related quality-assurance issues remain to be
      addressed. DISCUSSION: Randomized controlled studies are needed for a realistic
      assessment of the achievable benefits and unavoidable side effects of combined
      screening. For women whose risk of breast cancer is not elevated, mammography
      remains the standard screening method.

PMID- 19593400
TI  - Simple remedy.

PMID- 19593401
TI  - Silver underestimated.

PMID- 19593403
TI  - The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole
      blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and
      RAGE.
AB  - The cholinergic antiinflammatory pathway modulates inflammatory cytokine
      production through a mechanism dependent on the vagus nerve and the alpha7
      subunit of the nicotinic acetylcholine receptor. GTS-21 [3-(2,4
      dimethoxybenzylidene) anabaseine], a selective alpha7 agonist, inhibits
      inflammatory cytokine production in murine and human macrophages and in several
      models of inflammatory disease in vivo, but to date its antiinflammatory efficacy
      in human monocytes has not been characterized. We report here our findings that
      GTS-21 attenuates tumor necrosis factor (TNF) and interleukin 1beta levels in
      human whole blood activated by exposure to endotoxin. GTS-21 inhibited TNF
      production in endotoxin-stimulated primary human monocytes in vitro at the
      transcriptional level. The suppressive effect of GTS-21 was more potent than
      nicotine in whole blood and monocytes. Furthermore, GTS-21 attenuated TNF
      production in monocytes stimulated with peptidoglycan, polyinosinic-polycytidylic
      acid, CpG, HMGB1 (high-mobility group box 1 protein), and advanced glycation end
      product-modified albumin. GTS-21 decreased TNF levels in endotoxin-stimulated
      whole blood obtained from patients with severe sepsis. These findings establish
      the immunoregulatory effect of GTS-21 on human monocytes, and indicate the
      potential benefits of further exploration of GTS-21's therapeutic uses in human
      inflammatory disease.

PMID- 19593404
TI  - Coordinate control of expression of Nrf2-modulated genes in the human small
      airway epithelium is highly responsive to cigarette smoking.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is an oxidant-responsive
      transcription factor known to induce detoxifying and antioxidant genes. Cigarette
      smoke, with its large oxidant content, is a major stress on the cells of small
      airway epithelium, which are vulnerable to oxidant damage. We assessed the role
      of cigarette smoke in activation of Nrf2 in the human small airway epithelium in
      vivo. Fiberoptic bronchoscopy was used to sample the small airway epithelium in
      healthy-nonsmoker and healthy-smoker, and gene expression was assessed using
      microarrays. Relative to nonsmokers, Nrf2 protein in the small airway epithelium
      of smokers was activated and localized in the nucleus. The human homologs of 201
      known murine Nrf2-modulated genes were identified, and 13 highly smoking
      responsive Nrf2-modulated genes were identified. Construction of an Nrf2 index to
      assess the expression levels of these 13 genes in the airway epithelium of
      smokers showed coordinate control, an observation confirmed by quantitative PCR.
      This coordinate level of expression of the 13 Nrf2-modulated genes was
      independent of smoking history or demographic parameters. The Nrf2 index was used
      to identify two novel Nrf2-modulated, smoking-responsive genes, pirin (PIR) and
      UDP glucuronosyltransferase 1-family polypeptide A4 (UGT1A4). Both genes were
      demonstrated to contain functional antioxidant response elements in the promoter
      region. These observations suggest that Nrf2 plays an important role in
      regulating cellular defenses against smoking in the highly vulnerable small
      airway epithelium cells, and that there is variability within the human
      population in the Nrf2 responsiveness to oxidant burden.

PMID- 19593406
TI  - Short-term overeating induces insulin resistance in fat cells in lean human
      subjects.
AB  - Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity.
      Numerous prospective studies have reported on weight gain, insulin resistance,
      and insulin signaling in experimental animals, but not in humans. We examined
      insulin signaling in adipocytes from lean volunteers, before and at the end of a
      4-wk period of consuming a fast-food, high-calorie diet that led to weight gain.
      We also examined adipocytes from patients with T2D. During the high-calorie diet,
      subjects gained 10% body weight and 19% total body fat, but stayed lean (body
      mass index = 24.3 kg/m(2)) and developed moderate systemic insulin resistance.
      Similarly to the situation in T2D subjects, in subjects on the high-calorie diet,
      the amount of insulin receptors was reduced and phosphorylation of IRS1 at
      tyrosine and at serine-307 (human sequence, corresponding to murine serine-302)
      were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the
      phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine
      serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on
      the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation
      of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this
      study is the first to investigate insulin signaling during overeating in humans,
      and it demonstrates that T2D effects on intracellular insulin signaling already
      occur after 4 wks of a high-calorie diet and that the effects in humans differ
      from those in laboratory animals.

PMID- 19593405
TI  - A genomic score prognostic of outcome in trauma patients.
AB  - Traumatic injuries frequently lead to infection, organ failure, and death. Health
      care providers rely on several injury scoring systems to quantify the extent of
      injury and to help predict clinical outcome. Physiological, anatomical, and
      clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health
      Evaluation [APACHE], Injury Severity Score [ISS]) are utilized, with limited
      success, to predict outcome following injury. The recent development of
      techniques for measuring the expression level of all of a person's genes
      simultaneously may make it possible to develop an injury scoring system based on
      the degree of gene activation. We hypothesized that a peripheral blood leukocyte
      gene expression score could predict outcome, including multiple organ failure,
      following severe blunt trauma. To test such a scoring system, we measured gene
      expression of peripheral blood leukocytes from patients within 12 h of traumatic
      injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury
      provided gene expression data for the entire genome that were used to create a
      composite gene expression score for each patient. Total blood leukocytes were
      chosen because they are active during inflammation, which is reflective of poor
      outcome. The gene expression score combines the activation levels of all the
      genes into a single number which compares the patient's gene expression to the
      average gene expression in uninjured volunteers. Expression profiles from healthy
      volunteers were averaged to create a reference gene expression profile which was
      used to compute a difference from reference (DFR) score for each patient. This
      score described the overall genomic response of patients within the first 12 h
      following severe blunt trauma. Regression models were used to compare the
      association of the DFR, APACHE, and ISS scores with outcome. We hypothesized that
      patients with a total gene response more different from uninjured volunteers
      would tend to have poorer outcome than those more similar. Our data show that for
      measures of poor outcome, such as infections, organ failures, and length of
      hospital stay, this is correct. DFR scores were associated significantly with
      adverse outcome, including multiple organ failure, duration of ventilation,
      length of hospital stay, and infection rate. The association remained significant
      after adjustment for injury severity as measured by APACHE or ISS. A single score
      representing changes in gene expression in peripheral blood leukocytes within
      hours of severe blunt injury is associated with adverse clinical outcomes that
      develop later in the hospital course. Assessment of genome-wide gene expression
      provides useful clinical information that is different from that provided by
      currently utilized anatomic or physiologic scores.

PMID- 19593407
TI  - Nonerythropoietic tissue protective compounds are highly effective facilitators
      of wound healing.
AB  - Erythropoietin (EPO) is a type I cytokine that utilizes different receptor
      isoforms either to maintain hematopoiesis or protect against injuries that arise
      from widely diverse etiologies. EPO also facilitates healing by reducing
      inflammation and mobilizing endothelial progenitor cells to participate in
      restorative neoangiogenesis, but it is unclear which EPO receptor isoform is
      responsible for healing and whether this receptor use varies according to the
      type of wound. In the present studies carried out in the rat, we have utilized
      receptor-selective derivatives of EPO to determine which receptor type operates
      in (i) a nonischemic wound (skin punch biopsy), (ii) a permanently ischemic wound
      (raised musculocutaneous flap), (iii) an intermittent ischemic reperfusion wound
      (pressure or decubitus ulcer), or (iv) wounds complicated by infection (cecal
      ligation and perforation). Using these models, we demonstrate that
      nonerythropoietic tissue protective compounds administered immediately following
      injury limit wound size and accelerate eschar closure independent of wound type.
      Moreover, in a model of peritonitis-induced adhesions, daily administration of
      the nonerythropoietic derivative carbamyl-EPO (10 microg/kg-bw) was associated
      with significantly lower serum TNFalpha concentration, illness scores, increased
      survival, as well as decreased adhesion formation. These results confirm that
      wound healing is mediated by the tissue protective receptor isoform and argue
      that nonerythropoietic tissue protective molecules constitute promising new.

PMID- 19593408
TI  - The immunohistochemical expression of growth hormone-releasing hormone receptor
      splice variant 1 is a favorable prognostic marker in colorectal cancer.
AB  - Hypothalamic growth hormone (GH)-releasing hormone (GHRH) regulates the release
      of GH from the pituitary gland. The receptors for GHRH (GHRH-R) are expressed
      predominantly in the pituitary. Recent evidence demonstrates that splice variants
      of the GHRH receptor are also expressed in several nonpituitary tissues, both
      normal and tumoral, as well as in cancer cell lines. The aim of this study was to
      investigate the expression of the splice variant 1 (SV-1) of GHRH-R in colorectal
      cancer (CRC). Seventy patients who underwent partial colectomy for CRC were
      enrolled in the study. Immunohistochemical expression of SV-1 was studied in
      paraffin-embedded sections of patient tumor tissue. A cytoplasmic supranuclear
      expression of SV-1 was observed in CRC as well as in the normal colon mucosa.
      Tumor grade and pathological stage were negatively correlated with expression of
      SV-1 (P = 0.012 and P = 0.013, respectively). CRCs metastatic to the liver showed
      a lower expression of SV-1 than did primary tumors, but this difference was not
      statistically significant. Kaplan-Meier and Cox univariate survival analyses
      indicated an improved survival time in patients with high SV-1 compared with
      those with low GHRH-R expression, but this difference was not statistically
      significant. The immunohistochemical expression of SV-1 seems to be a favorable
      prognostic factor in CRC.

PMID- 19593410
TI  - Does splenectomy protect against immune-mediated complications in blunt trauma
      patients?
AB  - Activation of the innate immune system results from severe trauma and the
      resultant systemic inflammatory response is thought to mediate remote organ
      injury. In animal models, vagal-mediated innate immune responses have been shown
      to modulate proinflammatory cytokine release in response to trauma or sepsis. In
      those models, vagal nerve transaction and splenectomy decreased cytokine release
      and protected against lung injury and mortality. We hypothesized that, if similar
      mechanisms are active in humans, patients who require splenectomy for trauma
      would have better outcomes than injured patients without splenectomy. We
      performed a retrospective cohort study on 46,858 patients who sustained blunt
      liver or spleen injury utilizing the 2002 National Trauma Data Bank (NTDB). Blunt
      trauma patients who underwent splenectomy were compared with all patients with
      splenic injuries. Demographic parameters and the following outcome variables were
      compared: mortality, hospital length of stay (LOS), ICU length of stay (ILOS),
      mean ventilator days (VENT), and incidence of acute respiratory distress syndrome
      (ARDS). Groups were compared controlling for age, gender, injury severity score
      (ISS), emergency department (ED) blood pressure, and ED base deficit (BD) using
      multiple regression analyses. Patients that underwent splenectomy had
      significantly shorter LOS than patients who were managed nonoperatively or with
      splenorrhaphy: LOS,15.1 versus 19.3 d, P = 0.002; ILOS, 7.8 versus 10.6 d, P <
      0.001; and VENT, 7.1 versus 11.4 d, P < 0.001. Adjusted mortality rates (OR 1.02;
      95% CI 0.98-1.05; P = 0.29) and the reported incidence of ARDS were not
      significantly different between the two groups (2.4% versus 3.6%; P = 0.213).
      Patients who underwent splenectomy demonstrated better secondary outcomes than
      patients who were managed nonoperatively or with splenorrhaphy, even when
      controlling for injury severity and physiologic derangements. It is possible that
      the improved outcomes seen in the group undergoing splenectomy were due to
      favorable modulation of the human innate immune inflammatory response after
      trauma.

PMID- 19593409
TI  - Cadmium concentrations in blood and seminal plasma: correlations with sperm
      number and motility in three male populations (infertility patients, artificial
      insemination donors, and unselected volunteers).
AB  - To investigate a possible common environmental exposure that may partially
      explain the observed decrease in human semen quality, we correlated seminal
      plasma and blood cadmium levels with sperm concentration and sperm motility. We
      studied three separate human populations: group 1, infertility patients (Long
      Island, NY, USA); group 2, artificial insemination donors (AID) (Rochester, NY,
      USA); and group 3, general population volunteers (Rochester, NY, USA).
      Information about confounding factors was collected by questionnaire. Seminal
      plasma cadmium did not correlate with blood cadmium (Spearman correlation, n =
      91, r = -0.092, P = 0.386, NS). Both blood and seminal plasma cadmium were
      significantly higher among infertility patients than the other subjects studied
      (for example, median seminal plasma cadmium was 0.282 microg/L in infertility
      patients versus 0.091 microg/L in AID and 0.092 microg/L in general population
      volunteers; Kruskal-Wallis test, P < 0.001). The percentage of motile sperm and
      sperm concentration correlated inversely with seminal plasma cadmium among the
      infertility patients (r = -0.201, P < 0.036 and r = -0.189, P < 0.05,
      respectively), but not in the other two groups. Age (among infertility patients)
      was the only positive confounder correlating with seminal plasma cadmium. To
      validate our human findings in an animal model, we chronically exposed adolescent
      male Wistar rats to low-moderate cadmium in drinking water. Though otherwise
      healthy, the rats exhibited decreases in epididymal sperm count and sperm
      motility associated with cadmium dose and time of exposure. Our human and rat
      study results are consistent with the hypothesis that environmental cadmium
      exposures may contribute significantly to reduced human male sperm concentration
      and sperm motility.

PMID- 19593411
TI  - Genome-wide association for smoking cessation success: participants in a trial
      with adjunctive denicotinized cigarettes.
AB  - The ability to quit smoking successfully displays substantial heritability in
      classical and molecular genetic studies. Twin studies suggest that some of the
      genetics for the ability to quit overlap with genetic components of nicotine
      dependence, but many do not. Genome-wide association (GWA) studies have
      demonstrated haplotypes that distinguish successful quitters from individuals who
      were not able to quit smoking in: i) clinical trials that employed nicotine
      replacement; ii) clinical trials that employed bupropion; and iii) community
      quitter samples. We now report novel GWA results from participants in a clinical
      trial that document the efficacy of adjunctive use of denicotinized cigarettes.
      These results buttress data from our prior GWA studies of smoking cessation. They
      suggest that ability to change smoking behavior using denicotinized cigarettes
      shares substantial underlying genetics with the ability to change this behavior
      in community settings or in response to treatments with nicotine replacement or
      bupropion.

PMID- 19593414
TI  - The next practice.

PMID- 19593412
TI  - Spermine protects mice against lethal sepsis partly by attenuating surrogate
      inflammatory markers.
AB  - The pathogenesis of sepsis is partly attributable to dysregulated inflammatory
      response mediated by pathogen-associated molecular patterns (PAMPs) (for example,
      endotoxin) and damage-associated molecular patterns (DAMPs) (for example, high
      mobility group box 1 [HMGB1]). An endogenous ubiquitous polyamine, spermine,
      inhibits endotoxin-induced cytokine release in vitro, but its capacities to
      attenuate sepsis- and HMGB1-induced inflammatory responses was previously
      unknown. We thus tested the hypothesis that spermine protects mice against lethal
      sepsis by attenuating sepsis-induced local and systemic inflammatory responses.
      Intraperitoneal (i.p.) administration of spermine (10 mg/kg, twice daily, for 3
      d) conferred a significant protection against lethal sepsis. The protective
      effects were associated with a significant reduction in peritoneal and serum
      levels of several surrogate markers of sepsis (for example, Interleukin-6 [IL-6],
      keratinocyte-derived chemokine [KC], monocytes chemoattractant protein-1 [MCP-1],
      macrophage inflammatory protein-2 [MIP-2], tissue inhibitor of metalloproteinase
      1 [TIMP-1], soluble tumor necrosis factor-alpha receptor I [sTNFRI], and soluble
      tumor necrosis factor-alpha receptor II [sTNFRII]) during a late stage of sepsis.
      In vitro, spermine effectively inhibited HMGB1-induced release of the above
      surrogate markers in peritoneal macrophages. Thus, spermine confers protection
      against lethal sepsis partly by attenuating sepsis- and HMGB1-induced
      inflammatory responses.

PMID- 19593413
TI  - Molecularly targeted therapies for dysimmune neuropathies.
AB  - Conventional treatment options, including corticosteroids, intravenous
      immunoglobulin, or plasma exchange, often fail to treat dysimmune neuropathies,
      such as chronic inflammatory demyelinating polyneuropathy, multifocal motor
      neuropathy, and monoclonal gammopathy with its subtypes. Therefore, a significant
      percentage of patients require adjunctive immunosuppressive therapies.
      Considering that even immunosuppressive agents often are ineffective and/or
      associated with significant toxicities, the need for the development of safe and
      effective new treatment options is rising. Currently, several monoclonal
      antibodies (MAbs) have been tested in open-label small-sized studies or even in
      single cases so as to establish future directions in the therapy of diseases of
      the peripheral nervous system (PNS). Rituximab, an MAb targeting against the B
      cell surface membrane protein CD20, is the most widely used and promising MAb for
      the treatment of dysimmune neuropathies, especially for those in which
      immunoglobulin M (IgM) autoantibodies are pathogenetically involved. The efficacy
      of alemtuzumab, bevacizumab, and etanercept to treat various forms of dysimmune
      neuropathies is currently under investigation. This review looks critically at
      recent developments in molecularly targeted therapies for dysimmune neuropathies
      and also highlights areas of future research to pursue.

PMID- 19593415
TI  - Head impacts during high school football: a biomechanical assessment.
AB  - CONTEXT: Little is known about the impact biomechanics sustained by players
      during interscholastic football. OBJECTIVE: To characterize the location and
      magnitude of impacts sustained by players during an interscholastic football
      season. DESIGN: Observational design. SETTING: On the field. PATIENTS OR OTHER
      PARTICIPANTS: High school varsity football team (n = 35; age = 16.85 +/- 0.75
      years, height = 183.49 +/- 5.31 cm, mass = 89.42 +/- 12.88 kg). MAIN OUTCOME
      MEASURE(S): Biomechanical variables (linear acceleration, rotational
      acceleration, jerk, force, impulse, and impact duration) related to head impacts
      were categorized by session type, player position, and helmet impact location.
      RESULTS: Differences in grouping variables were found for each impact descriptor.
      Impacts occurred more frequently and with greater intensity during games. Linear
      acceleration was greatest in defensive linemen and offensive skill players and
      when the impact occurred at the top of the helmet. The largest rotational
      acceleration occurred in defensive linemen and with impacts to the front of the
      helmet. Impacts with the highest-magnitude jerk, force, and impulse and shortest
      duration occurred in the offensive skill, defensive line, offensive line, and
      defensive skill players, respectively. Top-of-the-helmet impacts yielded the
      greatest magnitude for the same variables. CONCLUSIONS: We are the first to
      provide a biomechanical characterization of head impacts in an interscholastic
      football team across a season of play. The intensity of game play manifested with
      more frequent and intense impacts. The highest-magnitude variables were
      distributed across all player groups, but impacts to the top of the helmet
      yielded the highest values. These high school football athletes appeared to
      sustain greater accelerations after impact than their older counterparts did. How
      this finding relates to concussion occurrence has yet to be elucidated.

PMID- 19593416
TI  - Alterations in knee kinematics and dynamic stability associated with chronic
      ankle instability.
AB  - CONTEXT: Chronic ankle instability (CAI) has been previously and separately
      associated with deficits in dynamic stability and proximal joint neuromuscular
      alterations, but how the 2 factors relate is unclear. OBJECTIVE: To examine the
      contributions of lower extremity kinematics during an assessment of dynamic
      stability in participants with CAI. DESIGN: Repeated-measures case-control
      design. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty
      eight volunteers were categorized into groups of those with unilateral CAI (10
      men, 9 women; age = 20.3 +/- 2.9 years, height = 1.77 +/- 0.1 m, mass = 76.19 +/-
      13.19 kg) and those without (10 men, 9 women; age = 23.1 +/- 3.9 years, height =
      1.72 +/- 0.1 m, mass = 72.67 +/- 16.0 kg). INTERVENTION(S): Participants
      performed 10 jump landings on each limb with a rest period between test limbs.
      MAIN OUTCOME MEASURE(S): Ankle plantar flexion, knee flexion, and hip flexion
      were captured with an electromagnetic tracking device at the point of ground
      impact. Ground reaction force data were used to calculate time to stabilization
      in the anteroposterior and mediolateral planes. RESULTS: For the anteroposterior
      plane, we found a group-by-side interaction (P = .003), with the injured side of
      the CAI group demonstrating reduced dynamic stability. For knee flexion, a group
      main effect (P = .008) showed that the CAI group landed with less knee flexion
      than the control group. CONCLUSIONS: Diminished dynamic stability and decreased
      knee flexion angle at initial contact were apparent in the CAI group and may play
      a role in contributing to CAI. This altered kinematic pattern may influence
      preventive and therapeutic interventions for those with CAI.

PMID- 19593417
TI  - Generalized joint laxity associated with increased medial foot loading in female
      athletes.
AB  - CONTEXT: The relationship between generalized joint laxity and plantar pressure
      distribution of the foot and the potential implications for lower extremity
      injury have not been studied. OBJECTIVE: To determine the relationship between
      generalized joint laxity and dynamic plantar pressure distribution. We
      hypothesized that individuals with greater generalized joint laxity, or
      hypermobility, would have greater dynamic medial midfoot pressure and loading
      during walking than nonhypermobile individuals. DESIGN: Case control. SETTING:
      Institutional biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Participants included 112 female soccer players between 11 and 21 years of age.
      MAIN OUTCOME MEASURE(S): Each participant was tested for generalized joint laxity
      using the Beighton and Horan Joint Mobility Index (BHJMI; range, 0-9) and was
      categorized as having either high (BHJMI score >or=4) or low (BHJMI score <4)
      generalized joint laxity. Peak pressure and maximum force were calculated from a
      dynamic, barefoot plantar pressure distribution system. RESULTS: Peak pressure
      and maximum force were greater in the 27 participants categorized as having high
      generalized joint laxity than in the 85 participants categorized as having low
      generalized joint laxity. The midfoot region exhibited greater loading in
      participants with high generalized joint laxity than in the other participants.
      We found an effect of BHJMI classification in the medial midfoot; peak pressure
      in the dominant (F(1,109) = 11.262, P = .001) and nondominant (F(1,109) = 14.32,
      P < .001) sides and maximum force in the dominant (F(1,109) = 7.88, P = .006) and
      nondominant (F(1,109) = 9.18, P = .003) sides were greater in the high
      generalized joint laxity group than in the low generalized joint laxity group.
      CONCLUSIONS: Athletes classified as having high generalized joint laxity
      demonstrated increased midfoot loading. Delineation of risk factors for medial
      collapse of the foot, which include hypermobility in athletes, may help
      clinicians evaluate and prevent lower extremity injury with treatments, such as
      orthoses.

PMID- 19593418
TI  - Ankle bracing and the neuromuscular factors influencing joint stiffness.
AB  - CONTEXT: Health care professionals commonly prescribe external stabilization to
      decrease the incidence and severity of ankle sprains. The mechanism for this
      decrease is not clearly understood. Examining the effects of ankle bracing on
      biomechanical stability and influencing factors may provide important information
      regarding the neuromuscular effects of bracing. OBJECTIVE: To study the effects
      of 2 different ankle braces on the neuromuscular factors influencing ankle
      stiffness. DESIGN: Mixed-model repeated-measures design. SETTING: Research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-eight physically active
      participants composing 2 groups: 14 with unilateral functional ankle instability
      (age = 26.19 +/- 6.46 years, height = 166.07 +/- 12.90 cm, mass = 69.90 +/- 13.46
      kg) and 14 with bilaterally stable ankles (age = 23.76 +/- 5.82 years, height =
      174.00 +/- 11.67 cm, mass = 68.60 +/- 13.12 kg). INTERVENTION(S): Participants
      were fitted with surface electromyography electrodes over the peroneus longus,
      peroneus brevis, tibialis anterior, and soleus muscles. Each participant received
      transient motion oscillations to his or her ankle on a custom-built medial
      lateral swaying cradle in each of 3 conditions: no ankle brace (NB), lace-up
      brace (LU), and semirigid brace (SR). MAIN OUTCOME MEASURE(S): Ankle stiffness as
      measured by the cradle and preactivation levels (percentage of maximal voluntary
      isometric contraction) of the 4 test muscles. RESULTS: Stiffness levels increased
      across brace conditions (NB = 24.79 +/- 6.59 Nm/rad, LU = 28.29 +/- 7.05 Nm/rad,
      SR = 33.22 +/- 8.78 Nm/rad; F(2,52) = 66.185, P < .001). No differences were
      found between groups for rotational stiffness (stable = 27.36 +/- 6.17 Nm/rad,
      unstable = 30.18 +/- 8.21 Nm/rad; F(1,26) = 1.084, P = .307). Preactivation
      levels did not change for any of the tested muscles with the application of an
      ankle brace (F(2,52) = 1.326, P = .275). CONCLUSIONS: The increase in ankle
      rotational stiffness with the addition of an ankle brace and the lack of any
      demonstrable neuromuscular changes suggested ankle braces passively contributed
      to the stability of the system.

PMID- 19593419
TI  - Low burnout and high engagement levels in athletic trainers: results of a
      nationwide random sample.
AB  - OBJECTIVE: To assess the prevalence of occupational burnout, engagement, and
      somatic health complaints and the associations among these constructs experienced
      by certified athletic trainers (ATs). A secondary objective was to examine
      differences between men and women, those with more versus less postcertification
      experience, and ATs who worked in different occupational settings. DESIGN: Survey
      based, stratified, proportionate random sample of full-time ATs. SETTING: Data
      were collected online from ATs employed full time in the college or university,
      secondary school or youth, and industrial or clinical settings. PATIENTS OR OTHER
      PARTICIPANTS: Of 3998 invited ATs, 934 replied, for a response rate of 24%. The
      mean age of the participants was 33.84 +/- 8.29 years, and each AT worked with an
      average of 90 clients. MAIN OUTCOME MEASURE(S): The dependent variables were
      perceived stress, occupational burnout, engagement, and somatic health
      complaints. RESULTS: Although 17.2% of participants were in the most advanced
      stages of burnout, low levels of burnout and high degrees of occupational
      engagement were observed. Women ATs and those working in the college or
      university settings scored higher for burnout, whereas men and those in the
      clinical or industrial settings scored higher for engagement. Women also reported
      significantly more somatic health complaints than men did. CONCLUSIONS: The
      overall prevalence of burnout in ATs was relatively small, but sex and
      occupational-setting differences were observed and deserve greater scrutiny.

PMID- 19593420
TI  - Novice to expert practice via postprofessional athletic training education: a
      grounded theory.
AB  - OBJECTIVE: To discover the theoretic constructs that confirm, disconfirm, or
      extend the principles and their applications appropriate for National Athletic
      Trainers' Association (NATA)-accredited postprofessional athletic training
      education programs. DESIGN: Interviews at the 2003 NATA Annual Meeting & Clinical
      Symposia. SETTING: Qualitative study using grounded theory procedures. PATIENTS
      AND OTHER PARTICIPANTS: Thirteen interviews were conducted with postprofessional
      graduates. Participants were purposefully selected based on theoretic sampling
      and availability. DATA COLLECTION AND ANALYSIS: The transcribed interviews were
      analyzed using open coding, axial coding, and selective coding procedures. Member
      checks, reflective journaling, and triangulation were used to ensure
      trustworthiness. RESULTS: The participants' comments confirmed and extended the
      current principles of postprofessional athletic training education programs and
      offered additional suggestions for more effective practical applications.
      CONCLUSIONS: The emergence of this central category of novice to expert practice
      is a paramount finding. The tightly woven fabric of the 10 processes, when
      interlaced with one another, provides a strong tapestry supporting novice to
      expert practice via postprofessional athletic training education. The emergence
      of this theoretic position pushes postprofessional graduate athletic training
      education forward to the future for further investigation into the theoretic
      constructs of novice to expert practice.

PMID- 19593421
TI  - Curricular satisfaction levels of National Athletic Trainers' Association
      accredited postprofessional athletic training graduates.
AB  - CONTEXT: Academic programs rely on outcomes assessments to determine if changes
      in the curriculum are necessary. OBJECTIVE: To examine the overall satisfaction
      levels of graduates (2005-2006) of National Athletic Trainers' Association
      accredited postprofessional athletic training education programs as related to
      the 2002 Standards and Guidelines for Development and Implementation of NATA
      Accredited Post-Professional Graduate Athletic Training Education Programs.
      DESIGN: Original survey instrument and demographic questionnaire. SETTING: Online
      survey instrument. PATIENTS OR OTHER PARTICIPANTS: Of 211 survey recipients, 123
      returned surveys (58.29% response rate). MAIN OUTCOME MEASURE(S): Demographic
      information and satisfaction levels in 10 standard areas (depth of learning,
      breadth of learning, critical thinking, instructor availability, theoretic basis,
      writing skills, scholarly growth, community return, leadership, and overall
      program satisfaction) were obtained. Satisfaction scores were categorized into 10
      percentage brackets (eg, 80%-89%) for each standard area. RESULTS: No differences
      were noted in relation to any of the standard satisfaction areas for evaluation
      of time off from school. However, graduates who required more than the allotted
      amount of time to complete their degree were less satisfied in the areas of depth
      of learning (P = .027), breadth of learning (P = .001), instructor availability
      (P = .005), writing (P = .022), and overall program satisfaction (P = .016).
      CONCLUSIONS: Graduates were generally satisfied across all areas of their
      didactic curriculum. However, satisfaction levels were affected if graduates
      required more than the allotted amount of time to complete their degrees.

PMID- 19593422
TI  - Current sport-related concussion teaching and clinical practices of sports
      medicine professionals.
AB  - CONTEXT: Various consensus and position statements recommend a multifaceted
      approach when diagnosing a possible concussion. The effectiveness of these
      materials depends largely on their content being disseminated to educators and to
      those in the clinical setting. OBJECTIVE: To identify the concussion management
      methods and guidelines currently taught in the athletic training classroom and
      clinical settings and to track the dissemination of the Vienna guidelines
      throughout the educational curriculum. DESIGN: A 17-question Internet survey.
      SETTING: A Web link was e-mailed to the program directors and certified athletic
      trainers holding educational positions in athletic training at 300 accredited
      programs in the United States. PATIENTS OR OTHER PARTICIPANTS: 513 program
      directors and athletic trainers. MAIN OUTCOME MEASURE(S): Survey questions
      addressed education level, years of certification, employment setting, concussion
      assessment and return-to-play guidelines used in the clinical setting and the
      classroom, and clinical and teaching preferences for existing position statements
      and concussion grading systems. The Vienna guidelines' "simple" and "complex"
      definitions of concussions were provided with the return-to-play stepwise
      approach. RESULTS: The National Athletic Trainers' Association position statement
      was the most widely used method of assessing, managing (61%), and making return
      to-play decisions (47%) among participants. More than half of participants (66%)
      had never heard of the Vienna guidelines. After reading the Vienna guidelines'
      definitions and return-to-play criteria, nearly three-fourths of participants
      agreed with them. In addition, 68% said that they would use them, and 84%
      reported that they would teach them to students. CONCLUSIONS: The majority of
      program directors and certified athletic trainers used a multidimensional
      approach to assess and manage a concussion. The National Athletic Trainers'
      Association position statement and Vienna guidelines were underused in both the
      classroom and clinical settings.

PMID- 19593424
TI  - Keeping your head in the game: sport-specific imagery and anxiety among injured
      athletes.
AB  - CONTEXT: The use of sport-specific imagery during rehabilitation is sparse.
      Athletes who used imagery (either facilitative or debilitative) during injury
      rehabilitation were compared with injured athletes who did not use imagery.
      Return-to-practice anxiety in the groups was investigated also. OBJECTIVE: To (1)
      explore debilitative images used during rehabilitation, (2) examine athlete and
      injury characteristics in relation to variations in imagery content and return-to
      practice anxiety, (3) compare the frequency of imagery use early in injury
      rehabilitation with that just before return to practice, and (4) examine the
      relationship between image use and return-to-practice anxiety. DESIGN:
      Observational design. SETTING: Athletic training facilities. PATIENTS OR OTHER
      PARTICIPANTS: Thirty-six injured National Collegiate Athletic Association
      Division I collegiate athletes sustaining at least an 8-day practice suspension
      due to injury. MAIN OUTCOME MEASURE(S): Sport Imagery Questionnaire, Sport
      Anxiety Scale. RESULTS: Athletes used both facilitative and debilitative images
      during different phases of rehabilitation. Men used more sport skill, strategy,
      and excitement imagery content than did women, who reported higher scores for
      worry and concentration disruption than did men. Athletes used fewer images
      related to their sport skills and strategies early in rehabilitation than just
      before they returned to practice. Additionally, athletes who used more arousal
      and less strategic imagery experienced more somatic anxiety. CONCLUSIONS: Similar
      to research findings on healthy athletes, sport-specific image content in injured
      athletes is related to return-to-practice anxiety during rehabilitation, and some
      of the images were perceived as debilitative. Practitioners should advise injured
      athletes to use sport-specific imagery, especially that related to sport skills
      and strategies, but they should caution athletes against using arousal imagery,
      because it may elevate somatic anxiety before return to practice. Image content
      recommendations should encompass the cognitive and motivational functions of
      imagery, and the practitioner should assess if any image used by the athlete is
      debilitative.

PMID- 19593423
TI  - Age-related differences in neuropsychological testing among high school athletes.
AB  - CONTEXT: Clinicians have questioned the need to obtain annual baseline
      neuropsychological tests in high school athletes. If no difference among academic
      grades exists, annual baseline testing may not be necessary. OBJECTIVE: To
      examine differences at baseline testing on pencil-and-paper neuropsychological
      tests among grade levels in high school athletes. DESIGN: Cross-sectional,
      between-groups design. SETTING: Schools participating in a Georgia high school
      athletics association. PATIENTS OR OTHER PARTICIPANTS: High school football
      players (n = 198) in the 9th through 12th grades, with a mean age of 15.78 +/-
      1.16 years. MAIN OUTCOME MEASURE(S): Participants were divided into 4 groups by
      grade and were administered a symptom checklist and brief neuropsychological test
      battery. Grade level served as the independent variable. Symptom and individual
      test scores within the neuropsychological test battery served as dependent
      variables. RESULTS: Differences were noted among grades on the Trail Making Test
      A (F(3,194) = 3.23, P = .024, eta(2) = 0.048), Trail Making Test B (F(3,194) =
      3.93, P = .009, eta(2) = 0.057), Symbol Digit Modalities Test (F(3,194) = 4.38, P
      = .005, eta(2) = 0.064), dominant tap (F(3,194) = 3.14, P = .026, eta(2) =
      0.046), and nondominant tap (F(3,194) = 4.902, P = .003, eta(2) = 0.070). Using
      the Bonferroni correction (P <or= .00625), we found differences between the 9th
      grade and 11th and 12th grades. CONCLUSIONS: Baseline neuropsychological test
      scores in high school athletes improved as a function of age, with differences
      between the 9th grade and 11th and 12th grades. Because the differences were
      driven by 9th-grade test scores, baseline testing should be completed, at
      minimum, upon entrance into 9th and 10th grades; however, annual testing is still
      recommended until additional research is conducted.

PMID- 19593425
TI  - Body image, anthropometric measures, and eating-disorder prevalence in auxiliary
      unit members.
AB  - CONTEXT: Medical professionals have recognized eating disorders and related
      problems in competitive athletes. Auxiliary members (color guard, dance,
      majorettes) experience the same appearance-related pressures observed in sports
      commonly associated with eating disorders. OBJECTIVE: To estimate eating-disorder
      prevalence based on associated eating-disorder characteristics and behaviors in
      female auxiliary members and to compare perceived and ideal body images and
      anthropometric measurements between at-risk and not-at-risk participants for
      eating-disorder characteristics and behaviors. DESIGN: Cross-sectional design.
      SETTING: Three universities in the southeastern United States. PATIENTS OR OTHER
      PARTICIPANTS: Participants (n = 101, mean age = 19.2 +/- 1.2 years) represented 3
      auxiliary units, including color guard (n = 35), dance line (n = 47), and
      majorettes (n = 19). MAIN OUTCOME MEASURE(S): Participants self-reported
      menstrual history, height, and weight. Anthropometric measurements included
      height, weight, body fat percentage, and waist and hip circumferences. We
      screened for eating-disorder risk behavior with the Eating Attitudes Test (EAT)
      26 and for body dissatisfaction with the Figural Stimuli Survey. RESULTS: Based
      on the EAT-26, we estimated eating-disorder prevalence among members to measure
      29.7% (95% confidence interval = 20.8%, 38.6%). The EAT-26 results revealed that
      21% of participants used purgatives and 14% vomited to control weight or shape.
      The at-risk group had higher scores on the EAT-26 total (P <or= .01) and on the
      dieting (P <or= .01), oral control (P = .02), and bulimia (P = .01) subscales.
      Hip circumference (P = .01), self-reported weight (P = .03), measured weight (P =
      .04), difference between measured and preferred weights (P = .02), and calculated
      target weight (P = .02) were different between the at-risk and not-at-risk
      groups. CONCLUSIONS: Collegiate auxiliary unit members may have an unacceptable
      prevalence of eating disorders. Our results validate concerns that auxiliary
      members may exhibit an unacceptable eating-disorder risk, highlighting the need
      to examine and address unhealthy weight-management behaviors independent of
      eating-disorder status.

PMID- 19593426
TI  - Longitudinal evaluation of Journal of Athletic Training author credentials:
      implications for future research engagement in athletic training.
AB  - PURPOSE: To employ retrospective trend analysis in an attempt to provide a
      layered description of the relative contribution (per credential) of clinical
      athletic trainers (those without terminal degrees) to authoring scientific
      literature in the Journal of Athletic Training (JAT). From these data, our
      secondary purpose was to evaluate trends relative to changes in journal policy
      and increased educational rigor or professional limitations over the past decade,
      discussing how they may affect the potential for clinical athletic trainers to
      contribute to JAT. DESIGN: Exploratory study design with trend analysis.
      PARTICIPANTS: Data collection and analysis included a trend evaluation of the
      credentials of clinical athletic trainer authors in JAT and the teams (by
      credential) of authorship to determine the credentials of authors who published
      in JAT. MEASUREMENTS: Longitudinal tabulation of JAT author credentials from 1995
      through 2007. RESULTS: We noted increases in the absolute number of research
      articles per volume and the number of authors per article and a decrease in the
      relative percentage of authors who were athletic trainers. The results also
      suggested that the bachelor of science degree (BS-ATC, representative of clinical
      athletic trainers without advanced degrees) and Doctor of Medicine (MD)
      credential may be underrepresented in JAT authorship. CONCLUSIONS: Postgraduate
      research training may facilitate scientific article contribution by athletic
      trainers. Continued evolution in the athletic training evidence-based medicine
      movement should foster research-based mentorship during education. Cultivating
      collaborations between clinical athletic trainers and research teams may also
      promote outcomes assessment trials, which will benefit athletic training
      practices.

PMID- 19593428
TI  - Certainty in categorical judgment of size.
AB  - The certainty of judgment (or self-confidence) has been traditionally studied in
      relation with the accuracy. However, from an observer's viewpoint, certainty may
      be more closely related to the consistency of judgment than to its accuracy:
      consistent judgments are objectively certain in the sense that any external
      observer can rely on these judgments to happen. The regions of certain vs.
      uncertain judgment were determined in a categorical rating experiment. The
      participants rated the size of visual objects on a 5-point scale. There was no
      feedback so that there were no constraints of accuracy. Individual data was
      examined, and the ratings were characterized by their frequency distributions (or
      categories). The main result was that the individual categories always presented
      a core of certainty where judgment was totally consistent, and large peripheries
      where judgment was inconsistent. In addition, the geometry of cores and
      boundaries exhibited several phenomena compatible with the literature on visual
      categorical judgment. The ubiquitous presence of cores in absence of accuracy
      constraints provided insights about objective certainty that may complement the
      literature on subjective certainty (self-confidence) and the accuracy of
      judgment.

PMID- 19593427
TI  - Consensus statement on concussion in sport: the 3rd International Conference on
      Concussion in Sport held in Zurich, November 2008.

PMID- 19593429
TI  - Induction of thyroid gene expression and radioiodine uptake in melanoma cells:
      novel therapeutic implications.
AB  - Both the MAP kinase and PI3K/Akt pathways play an important role in the
      pathogenesis of melanoma. We conducted the present study to test the hypothesis
      that targeting the two pathways to potently induce cell inhibition accompanied
      with thyroid iodide-handling gene expression for adjunct radioiodine ablation
      could be a novel effective therapeutic strategy for melanoma. We used specific
      shRNA approaches and inhibitors to individually or dually suppress the MAP kinase
      and PI3K/Akt pathways and examined the effects on a variety of molecular and
      cellular responses of melanoma cells that harbored activating genetic alterations
      in the two pathways. Suppression of the MAP kinase and PI3K/Akt pathways showed
      potent anti-melanoma cell effects, including the inhibition of cell
      proliferation, transformation and invasion, induction of G(0)/G(1) cell cycle
      arrest and, when the two pathways were dually suppressed, cell apoptosis.
      Remarkably, suppression of the two pathways, particularly simultaneous
      suppression of them, also induced expression of genes that are normally expressed
      in the thyroid gland, such as the genes for sodium/iodide symporter and thyroid
      stimulating hormone receptor. Melanoma cells were consequently conferred the
      ability to take up radioiodide. We conclude that dually targeting the MAP kinase
      and PI3K/Akt pathways for potent cell inhibition coupled with induction of
      thyroid gene expression for adjunct radioiodine ablation therapy may prove to be
      a novel and effective therapeutic strategy for melanoma.

PMID- 19593430
TI  - Energy stores are not altered by long-term partial sleep deprivation in
      Drosophila melanogaster.
AB  - Recent human studies reveal a widespread association between short sleep and
      obesity. Two hypotheses, which are not mutually exclusive, might explain this
      association. First, genetic factors that reduce endogenous sleep times might also
      impact energy stores, an assertion that we confirmed in a previous study. Second,
      metabolism may be altered by chronic partial sleep deprivation. Here we address
      the second assertion by measuring the impact of long-term partial sleep
      deprivation on energy stores using Drosophila as a model. We subjected flies to
      long-term partial sleep deprivation via two different methods: a mechanical
      stimulus and a light stimulus. We then measured whole-body triglycerides and
      glycogen, two important sources of energy for the fly, and compared them to un
      stimulated controls. We also measured changes in energy stores in response to a
      random circadian clock shift. Sex and line-dependent alterations in glycogen
      and/or triglyceride levels occurred in response to the circadian clock shift and
      in flies subjected to a single night of sleep deprivation using light. Thus,
      consistent with previous studies, our findings suggest that acute sleep loss and
      changes to the circadian clock can alter metabolism. Significant changes in
      energy stores were also observed when flies were subjected to chronic sleep loss
      via the mechanical stimulus, although not the light stimulus. Interestingly,
      mechanical stimulation resulted in the same change in energy stores even when it
      was not associated with sleep deprivation, suggesting that the changes are caused
      by stress rather than sleep loss. These findings emphasize the importance of
      taking stress into account when evaluating the relationship between sleep loss
      and metabolism.

PMID- 19593432
TI  - In situ determination of the effects of lead and copper on cyanobacterial
      populations in microcosms.
AB  - BACKGROUND: Biomass has been studied as biomarker to evaluate the effect of heavy
      metals on microbial communities. Nevertheless, the most important methodological
      problem when working with natural and artificial microbial mats is the difficulty
      to evaluate changes produced on microorganism populations that are found in
      thicknesses of just a few mm depth. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      applied for first time a recently published new method based on confocal laser
      scanning microscopy and image-program analysis to determine in situ the effect of
      Pb and Cu stress in cyanobacterial populations. CONCLUSIONS/SIGNIFICANCE: The
      results showed that both in the microcosm polluted by Cu and by Pb, a drastic
      reduction in total biomass for cyanobacterial and Microcoleus sp. (the dominant
      filamentous cyanobacterium in microbial mats) was detected within a week.
      According to the data presented in this report, this biomass inspection has a
      main advantage: besides total biomass, diversity, individual biomass of each
      population and their position can be analysed at microscale level. CLSM-IA could
      be a good method for analyzing changes in microbial biomass as a response to the
      addition of heavy metals and also to other kind of pollutants.

PMID- 19593431
TI  - Biomarkers for early and late stage chronic allograft nephropathy by
      proteogenomic profiling of peripheral blood.
AB  - BACKGROUND: Despite significant improvements in life expectancy of kidney
      transplant patients due to advances in surgery and immunosuppression, Chronic
      Allograft Nephropathy (CAN) remains a daunting problem. A complex network of
      cellular mechanisms in both graft and peripheral immune compartments complicates
      the non-invasive diagnosis of CAN, which still requires biopsy histology. This is
      compounded by non-immunological factors contributing to graft injury. There is a
      pressing need to identify and validate minimally invasive biomarkers for CAN to
      serve as early predictors of graft loss and as metrics for managing long-term
      immunosuppression. METHODS: We used DNA microarrays, tandem mass spectroscopy
      proteomics and bioinformatics to identify genomic and proteomic markers of mild
      and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77
      total) of kidney transplant patients with biopsy-documented histology. FINDINGS:
      Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for
      moderate/severe CAN. A consensus analysis reveals 393 (mild) and 63
      (moderate/severe) final candidates as CAN markers with predictive accuracy of 80%
      (mild) and 92% (moderate/severe). Proteomic profiles show over 500 candidates
      each, for both stages of CAN including 302 proteins unique to mild and 509 unique
      to moderate/severe CAN. CONCLUSIONS: This study identifies several unique
      signatures of transcript and protein biomarkers with high predictive accuracies
      for mild and moderate/severe CAN, the most common cause of late allograft
      failure. These biomarkers are the necessary first step to a proteogenomic
      classification of CAN based on peripheral blood profiling and will be the targets
      of a prospective clinical validation study.

PMID- 19593433
TI  - Crystal structure of the C-terminal cytoplasmic domain of non-structural protein
      4 from mouse hepatitis virus A59.
AB  - BACKGROUND: The replication of coronaviruses takes place on cytoplasmic double
      membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three
      trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to be
      membrane anchors of the coronavirus replication complex. Nsp4 is localized to the
      ER membrane when expressed alone but is recruited into the replication complex in
      infected cells. It is revealed to contain four trans-membrane regions and its N-
      and C-termini are exposed to the cytosol. METHODOLOGY/PRINCIPAL FINDINGS: We have
      determined the crystal structures of the C-terminal hydrophilic domain of nsp4
      (nsp4C) from MHV strain A59 and a C425S site-directed mutant. The highly
      conserved 89 amino acid region from T408 to Q496 is shown to possess a new fold.
      The wild-type (WT) structure features two monomers linked by a Cys425-Cys425
      disulfide bond in one asymmetric unit. The monomers are arranged with their N-
      and C-termini in opposite orientations to form an "open" conformation. Mutation
      of Cys425 to Ser did not affect the monomer structure, although the mutant dimer
      adopts strikingly different conformations by crystal packing, with the cross
      linked C-termini and parallel N-termini of two monomers forming a "closed"
      conformation. The WT nsp4C exists as a dimer in solution and can dissociate
      easily into monomers in a reducing environment. CONCLUSIONS/SIGNIFICANCE: As
      nsp4C is exposed in the reducing cytosol, the monomer of nsp4C should be
      physiological. This structure may serve as a basis for further functional studies
      of nsp4.

PMID- 19593434
TI  - A multidrug ABC transporter with a taste for salt.
AB  - BACKGROUND: LmrA is a multidrug ATP-binding cassette (ABC) transporter from
      Lactococcus lactis with no known physiological substrate, which can transport a
      wide range of chemotherapeutic agents and toxins from the cell. The protein can
      functionally replace the human homologue ABCB1 (also termed multidrug resistance
      P-glycoprotein MDR1) in lung fibroblast cells. Even though LmrA mediates ATP
      dependent transport, it can use the proton-motive force to transport substrates,
      such as ethidium bromide, across the membrane by a reversible, H(+)-dependent,
      secondary-active transport reaction. The mechanism and physiological context of
      this reaction are not known. METHODOLOGY/PRINCIPAL FINDINGS: We examined ion
      transport by LmrA in electrophysiological experiments and in transport studies
      using radioactive ions and fluorescent ion-selective probes. Here we show that
      LmrA itself can transport NaCl by a similar secondary-active mechanism as
      observed for ethidium bromide, by mediating apparent H(+)-Na(+)-Cl(-) symport.
      Remarkably, LmrA activity significantly enhances survival of high-salt adapted
      lactococcal cells during ionic downshift. CONCLUSIONS/SIGNIFICANCE: The
      observations on H(+)-Na(+)-Cl(-) co-transport substantiate earlier suggestions of
      H(+)-coupled transport by LmrA, and indicate a novel link between the activity of
      LmrA and salt stress. Our findings demonstrate the relevance of investigations
      into the bioenergetics of substrate translocation by ABC transporters for our
      understanding of fundamental mechanisms in this superfamily. This study
      represents the first use of electrophysiological techniques to analyze substrate
      transport by a purified multidrug transporter.

PMID- 19593435
TI  - Genomes2Drugs: identifies target proteins and lead drugs from proteome data.
AB  - BACKGROUND: Genome sequencing and bioinformatics have provided the full
      hypothetical proteome of many pathogenic organisms. Advances in microarray and
      mass spectrometry have also yielded large output datasets of possible target
      proteins/genes. However, the challenge remains to identify new targets for drug
      discovery from this wealth of information. Further analysis includes
      bioinformatics and/or molecular biology tools to validate the findings. This is
      time consuming and expensive, and could fail to yield novel drugs if protein
      purification and crystallography is impossible. To pre-empt this, a researcher
      may want to rapidly filter the output datasets for proteins that show good
      homology to proteins that have already been structurally characterised or
      proteins that are already targets for known drugs. Critically, those researchers
      developing novel antibiotics need to select out the proteins that show close
      homology to any human proteins, as future inhibitors are likely to cross-react
      with the host protein, causing off-target toxicity effects later in clinical
      trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have
      developed a free online resource called Genomes2Drugs which ranks sequences to
      identify proteins that are (i) homologous to previously crystallized proteins or
      (ii) targets of known drugs, but are (iii) not homologous to human proteins. When
      tested using the Plasmodium falciparum malarial genome the program correctly
      enriched the ranked list of proteins with known drug target proteins.
      CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are
      likely to succeed in drug discovery pipelines. This free online resource helps in
      the identification of potential drug targets. Importantly, the program further
      highlights proteins that are likely to be inhibited by FDA-approved drugs. These
      drugs can then be rapidly moved into Phase IV clinical studies under 'change-of
      application' patents.

PMID- 19593436
TI  - Involvement of the post-transcriptional regulator Hfq in Yersinia pestis
      virulence.
AB  - BACKGROUND: Yersinia pestis is the causative agent of plague, which is
      transmitted primarily between fleas and mammals and is spread to humans through
      the bite of an infected flea or contact with afflicted animals. Hfq is proposed
      to be a global post-transcriptional regulator that acts by mediating interactions
      between many regulatory small RNAs (sRNAs) and their mRNA targets. Sequence
      comparisons revealed that Y. pestis appears to produce a functional homologue of
      E. coli Hfq. METHODOLOGY AND PRINCIPAL FINDINGS: Phenotype comparisons using in
      vitro assays demonstrated that Y. pestis Hfq was involved in resistance to
      H(2)O(2), heat and polymyxin B and contributed to growth under nutrient-limiting
      conditions. The role of Hfq in Y. pestis virulence was also assessed using
      macrophage and mouse infection models, and the gene expression affected by Hfq
      was determined using microarray-based transcriptome and real time PCR analysis.
      The macrophage infection assay showed that the Y. pestis hfq deletion strain did
      not have any significant difference in its ability to associate with J774A.1
      macrophage cells. However, hfq deletion appeared to significantly impair the
      ability of Y. pestis to resist phagocytosis and survive within macrophages at the
      initial stage of infection. Furthermore, the hfq deletion strain was highly
      attenuated in mice after subcutaneous or intravenous injection. Transcriptome
      analysis supported the results concerning the attenuated phenotype of the hfq
      mutant and showed that the deletion of the hfq gene resulted in significant
      alterations in mRNA abundance of 243 genes in more than 13 functional classes,
      about 23% of which are known or hypothesized to be involved in stress resistance
      and virulence. CONCLUSIONS AND SIGNIFICANCE: Our results indicate that Hfq is a
      key regulator involved in Y. pestis stress resistance, intracellular survival and
      pathogenesis. It appears that Hfq acts by controlling the expression of many
      virulence- and stress-associated genes, probably in conjunction with small
      noncoding RNAs.

PMID- 19593437
TI  - Differences between CusA and AcrB crystallisation highlighted by protein
      flexibility.
AB  - BACKGROUND: Until very recently, AcrB was the only Resistance Nodulation and cell
      Division transporter for which the structure has been elucidated. Towards a
      general understanding of this protein family, CusA and AcrB were compared.
      METHODOLOGY/PRINCIPAL FINDINGS: In dodecylmaltoside, AcrB crystallised in many
      different conditions, while CusA does not. This could be due to the difference in
      dynamic between these proteins as judged from limited proteolysis assays.
      Addition of various compounds, in particular heavy metal cations, stabilises
      CusA. CONCLUSION/SIGNIFICANCE: This approach could constitute a first step
      towards CusA crystallisation.

PMID- 19593438
TI  - Developmental control of a lepidopteran pest Spodoptera exigua by ingestion of
      bacteria expressing dsRNA of a non-midgut gene.
AB  - BACKGROUND: RNA interference (RNAi) induced through double stranded RNA (dsRNA)
      has been used widely to study gene function in insects. Recently, it has been
      reported that gene knockdown in several insects can be induced successfully
      through feeding with dsRNA. However, it is still unknown whether phenotypic
      silencing of genes not expressed in the midgut occurs after ingestion of insect
      dsRNA. PRINCIPAL FINDINGS: Using chitin synthase gene A (SeCHSA) as the target
      gene, which is expressed in the cuticle and tracheae of the lepidopteran pest
      Spodoptera exigua, we showed that the growth and development of S. exigua larvae
      fed Escherichia coli expressing dsRNA of SeCHSA was disturbed, resulting in
      lethality. In the 4th and 5th larval instars, prepupae, and pupae, the mean
      survival rates of insects fed the dsRNA-containing diet were 88.64%, 74.24%,
      68.43% and 62.63% respectively. The survival rates in the 5th instar larvae,
      prepupae and pupae stages were significantly lower than those of all controls,
      and significant lethality differences were also found between dsSeCHSA treatment
      and dsControl or ddH(2)O control in the 4th instar larvae. The effects of
      ingesting bacterially expressed dsRNA on transcription of the target gene, tissue
      structure, and survival rates of insects were dose-dependent. CONCLUSIONS: Our
      results suggest that SeCHSA dsRNA may be useful as a means of insect pest
      control.

PMID- 19593439
TI  - Exploration of the one-bead one-compound methodology for the design of prolyl
      oligopeptidase substrates.
AB  - Here we describe the design, synthesis and evaluation of the first solid-phase
      substrates for prolyl oligopeptidase (POP), a cytosolic serine peptidase
      associated with schizophrenia, bipolar affective disorder and related
      neuropsychiatric disorders. This study seeks to contribute to the future design
      of a one-bead one-compound (OBOC) peptide library of POP substrates, based on an
      intramolecular energy transfer substrate. Unexpectedly, the enzymatic evaluation
      of the substrates attached on solid-phase by means of the HMBA linker were
      cleaved through the ester bond, thereby suggesting an unknown esterase activity
      of POP, in addition to its known peptidase activity. By performing multiple
      activity assays, we have confirmed the esterase activity of this enzyme and its
      capacity to process the substrates on solid-phase. Finally, we tested a new
      linker, compatible with both the solid-phase peptide-synthesis used and the
      enzymatic assay, for application in the future design of an OBOC library.

PMID- 19593440
TI  - Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel
      and energy metabolism in primary rodent pancreatic beta-cells.
AB  - BACKGROUND: Glucagon like peptide-1 (GLP-1) and its analogue exendin-4 (Ex-4)
      enhance glucose stimulated insulin secretion (GSIS) and activate various
      signaling pathways in pancreatic beta-cells, in particular cAMP, Ca(2+) and
      protein kinase-B (PKB/Akt). In many cells these signals activate intermediary
      metabolism. However, it is not clear whether the acute amplification of GSIS by
      GLP-1 involves in part metabolic alterations and the production of metabolic
      coupling factors. METHODOLOGY/PRINICIPAL FINDINGS: GLP-1 or Ex-4 at high glucose
      caused release (approximately 20%) of the total rat islet insulin content over 1
      h. While both GLP-1 and Ex-4 markedly potentiated GSIS in isolated rat and mouse
      islets, neither had an effect on beta-cell fuel and energy metabolism over a 5
      min to 3 h time period. GLP-1 activated PKB without changing glucose usage and
      oxidation, fatty acid oxidation, lipolysis or esterification into various lipids
      in rat islets. Ex-4 caused a rise in [Ca(2+)](i) and cAMP but did not enhance
      energy utilization, as neither oxygen consumption nor mitochondrial ATP levels
      were altered. CONCLUSIONS/SIGNIFICANCE: The results indicate that GLP-1 barely
      affects beta-cell intermediary metabolism and that metabolic signaling does not
      significantly contribute to GLP-1 potentiation of GSIS. The data also indicate
      that insulin secretion is a minor energy consuming process in the beta-cell, and
      that the beta-cell is different from most cell types in that its metabolic
      activation appears to be primarily governed by a "push" (fuel substrate driven)
      process, rather than a "pull" mechanism secondary to enhanced insulin release as
      well as to Ca(2+), cAMP and PKB signaling.

PMID- 19593441
TI  - Darpp-32 and its truncated variant t-Darpp have antagonistic effects on breast
      cancer cell growth and herceptin resistance.
AB  - BACKGROUND: Herceptin (trastuzumab) is a humanized monoclonal antibody that is
      approved for the treatment of metastatic breast cancer patients whose tumors
      overexpress Her2 (erbB2/neu). Up to 70% of Her2-positive breast cancers
      demonstrate a response to Herceptin-based therapies, but resistance almost
      inevitably arises within a year of the initial response. To help understand the
      mechanism of Herceptin resistance, we isolated clonal variants of Her2-positive
      BT474 human breast cancer cells (BT/Her(R)) that are highly resistant to
      Herceptin. These cell lines exhibit sustained PI3K/Akt signaling as an essential
      component of Herceptin-resistant proliferation. Several genes in the protein
      kinase A (PKA) signaling network have altered expression in BT/Her(R) cells,
      including PPP1R1B, which encodes a 32 kDa protein known as Darpp-32 and its amino
      terminal truncated variant, t-Darpp. The purpose of the current work was to
      determine the role of Darpp-32 and t-Darpp in Herceptin resistance. METHODOLOGY
      AND RESULTS: We determined expression of Darpp-32 and t-Darpp in BT/Her(R) cells
      selected for resistance to Herceptin. Subsequently, cDNAs encoding the two
      isoforms of Darpp-32 were transfected, separately and together, into Her2
      positive SK-Br-3 breast cancer cells. Transfected cells were tested for
      resistance to Herceptin and Herceptin-mediated dephosphorylation of Akt. DNA
      binding activity by the cAMP response element binding protein (CREB) was also
      measured. We found that BT/Her(R) cells overexpressed t-Darpp but not Darpp-32.
      Moreover, t-Darpp overexpression in SK-Br-3 cells was sufficient for conferring
      resistance to Herceptin and Herceptin-mediated dephosphorylation of Akt. Darpp-32
      co-expression reversed t-Darpp's effects on Herceptin resistance and Akt
      phosphorylation. t-Darpp overexpression led to increased CREB binding activity,
      which was also reversible by Darpp-32. CONCLUSIONS: t-Darpp and Darpp-32 appear
      to have antagonistic effects on Herceptin resistance. We present a unified model
      by which these effects might be mediated via the PKA regulatory network.

PMID- 19593443
TI  - Cellular microvesicle pathways can be targeted to transfer genetic information
      between non-immune cells.
AB  - Eukaryotic cell communication is based on protein signaling cascades that require
      direct cell-cell apposition, or receptor engagement by secreted molecules. The
      transmission of genetic information is thought to be uncommon, apart from recent
      reports of exosomal RNA transfer in immune and glioblastoma cells. We wished to
      examine if existing microvesicle pathways could be directly targeted for the
      horizontal transfer of RNA genomes in less specialized cell types. Using
      replication-deficient retrovirus vector, studies herein confirm that a range of
      cells routinely sequester a small population of these RNA genomes in a non
      canonical compartment, refractory to antibody neutralization and unaffected by
      specific pharmacological inhibition of pathways involved in conventional viral
      trafficking. Our experiments further reveal the cytoplasmic colocalization of
      vector genomes with tetraspanin proteins as well as the PI-3-kinase sensitive
      trafficking and subsequent transmission to 2 degrees targets. Collectively, our
      results indicate a scalable process whereby cells route vector genomes to
      multivesicular bodies (MVB) for cytoplasmic trafficking and exosomal release. Our
      findings imply that cells can serve to deliver recombinant payload, targeted for
      the stable genetic modification of 2 degrees target cells.

PMID- 19593442
TI  - Mutant glycyl-tRNA synthetase (Gars) ameliorates SOD1(G93A) motor neuron
      degeneration phenotype but has little affect on Loa dynein heavy chain mutant
      mice.
AB  - BACKGROUND: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS)
      cause motor and sensory axon loss in the peripheral nervous system, and clinical
      phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form
      of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions
      in addition to its canonical role in protein synthesis through catalyzing the
      addition of glycine to cognate tRNAs. METHODOLOGY/PRINCIPAL FINDINGS: We have
      recently described a new mouse model with a point mutation in the Gars gene
      resulting in a cysteine to arginine change at residue 201. Heterozygous
      Gars(C201R/+) mice have locomotor and sensory deficits. In an investigation of
      genetic mutations that lead to death of motor and sensory neurons, we have
      crossed the Gars(C201R/+) mice to two other mutants: the TgSOD1(G93A) model of
      human amyotrophic lateral sclerosis and the Legs at odd angles mouse
      (Dync1h1(Loa)) which has a defect in the heavy chain of the dynein complex. We
      found the Dync1h1(Loa/+);Gars(C201R/+) double heterozygous mice are more impaired
      than either parent, and this is may be an additive effect of both mutations.
      Surprisingly, the Gars(C201R) mutation significantly delayed disease onset in the
      SOD1(G93A);Gars(C201R/+) double heterozygous mutant mice and increased lifespan
      by 29% on the genetic background investigated. CONCLUSIONS/SIGNIFICANCE: These
      findings raise intriguing possibilities for the study of pathogenetic mechanisms
      in all three mouse mutant strains.

PMID- 19593444
TI  - Chemicals possessing a neurotrophin-like activity on dopaminergic neurons in
      primary culture.
AB  - BACKGROUND: Neurotrophic factors have been shown to possess strong
      neuroprotective and neurorestaurative properties in Parkinson's disease patients.
      However the issues to control their delivery into the interest areas of the brain
      and their surgical administration linked to their unability to cross the blood
      brain barrier are many drawbacks responsible of undesirable side effects limiting
      their clinical use. A strategy implying the use of neurotrophic small molecules
      could provide an interesting alternative avoiding neurotrophin administration and
      side effects. In an attempt to develop drugs mimicking neurotrophic factors, we
      have designed and synthesized low molecular weight molecules that exhibit
      neuroprotective and neuritogenic potential for dopaminergic neurons. PRINCIPAL
      FINDINGS: A cell-based screening of an in-house quinoline-derived compound
      collection led to the characterization of compounds exhibiting both activities in
      the nanomolar range on mesencephalic dopaminergic neurons in spontaneous or 1
      methyl-4-phenylpyridinium (MPP(+))-induced neurodegeneration. This study provides
      evidence that rescued neurons possess a functional dopamine transporter and
      underlines the involvement of the extracellular signal-regulated kinase 1/2
      signaling pathway in these processes. CONCLUSION: Cell-based screening led to the
      discovery of a potent neurotrophic compound possessing expected physico-chemical
      properties for blood brain barrier penetration as a serious candidate for
      therapeutic use in Parkinson disease.

PMID- 19593446
TI  - Aquaculture enclosures relate to the establishment of feral populations of
      introduced species.
AB  - Many species introduced by humans for social and economic benefits have invaded
      new ranges by escaping from captivity. Such invasive species can negatively
      affect biodiversity and economies. Understanding the factors that relate to the
      establishment of feral populations of introduced species is therefore of great
      importance for managing introduced species. The American Bullfrog (Lithobates
      catesbeianus) is one species that has escaped from farms, and it is now found in
      the wild in China. In this study, we examined influences of two types of bullfrog
      farm (termed simple and elaborate farm enclosures) on the establishment of feral
      populations of this species in 137 water bodies in 66 plots in four provinces of
      China. The likelihood of establishment of bullfrog populations in water bodies in
      plots with simple enclosures (49/89 = 55.1%) was higher than those with elaborate
      enclosures (3/48 = 6.3%). Based on the Akaike Information Criterion, the minimum
      adequate model of generalized linear mixed models with a binomial error structure
      and a logit link function showed that the establishment or failure of bullfrog
      populations in water bodies was positively correlated with the presence of a
      simple enclosure, the number of bullfrogs raised and the presence of permanent
      water in a plot, but negatively correlated with distance from a bullfrog farm and
      the occurrence of frequent hunting. Results therefore suggest that a simple farm
      enclosure can increase the establishment of feral bullfrog populations compared
      with an elaborate enclosure. Our findings are the first to quantify the
      importance of improving farming enclosures to control and minimize the risk from
      introduced species.

PMID- 19593445
TI  - Expression of the Bcl-2 protein BAD promotes prostate cancer growth.
AB  - BAD, a pro-apoptotic protein of the Bcl-2 family, has recently been identified as
      an integrator of several anti-apoptotic signaling pathways in prostate cancer
      cells. Thus, activation of EGFR, GPCRs or PI3K pathway leads to BAD
      phosphorylation and inhibition of apoptosis. Increased levels of BAD in prostate
      carcinomas have also been reported. It appears contradictory that instead of
      limiting expression of pro-apoptotic protein, prostate cancer cells choose to
      increase BAD levels while keeping it under tight phosphorylation control.
      Analysis of the effect of BAD on prostate cancer xenografts has shown that
      increased BAD expression enhances tumor growth, while knockdown of BAD expression
      by shRNA inhibits tumor growth. Tissue culture experiments demonstrated that
      increased BAD expression stimulates proliferation of prostate cancer cells. These
      results suggest that increased expression of BAD provides a proliferative
      advantage to prostate tumors, while BAD dephosphorylation increases sensitivity
      of prostate cancer cells to apoptosis. Combination of proliferative and apoptotic
      properties prompts prostate cancer cells to be "addicted" to increased levels of
      phosphorylated BAD. Thus, kinases that phosphorylate BAD are plausible
      therapeutic targets; while monitoring BAD phosphorylation could be used to
      predict tumor response to treatments.

PMID- 19593447
TI  - Modeling the repertoire of true tumor-specific MHC I epitopes in a human tumor.
AB  - DNA replication has a finite measurable error rate, net of repair, in all cells.
      Clonal proliferation of cancer cells leads therefore to accumulation of random
      mutations. A proportion of these mutational events can create new immunogenic
      epitopes that, if processed and presented by an MHC allele, may be recognized by
      the adaptive immune system. Here, we use probability theory to analyze the
      mutational and epitope composition of a tumor mass in successive division cycles
      and create a double Polya model for calculating the number of truly tumor
      specific MHC I epitopes in a human tumor. We deduce that depending upon tumor
      size, the degree of genomic instability and the degree of death within a tumor,
      human tumors have several tens to low hundreds of new, truly tumor-specific
      epitopes. Parenthetically, cancer stem cells, due to the asymmetry in their
      proliferative properties, shall harbor significantly fewer mutations, and
      therefore significantly fewer immunogenic epitopes. As the overwhelming majority
      of the mutations in cancer cells are unrelated to malignancy, the mutation
      generated epitopes shall be specific for each individual tumor, and constitute
      the antigenic fingerprint of each tumor. These calculations highlight the
      benefits for personalization of immunotherapy of human cancer, and in view of the
      substantial pre-existing antigenic repertoire of tumors, emphasize the enormous
      potential of therapies that modulate the anti-cancer immune response by
      liberating it from inhibitory influences.

PMID- 19593448
TI  - Base flipping in tn10 transposition: an active flip and capture mechanism.
AB  - The bacterial Tn5 and Tn10 transposases have a single active site that cuts both
      strands of DNA at their respective transposon ends. This is achieved using a
      hairpin intermediate that requires the DNA to change conformation during the
      reaction. In Tn5 these changes are controlled in part by a flipped nucleoside
      that is stacked on a tryptophan residue in a hydrophobic pocket of the
      transposase. Here we have investigated the base flipping mechanism in Tn10
      transposition. As in Tn5 transposition, we find that base flipping takes place
      after the first nick and is required for efficient hairpin formation and
      resolution. Experiments with an abasic substrate show that the role of base
      flipping in hairpin formation is to remove the base from the DNA helix. Specific
      interactions between the flipped base and the stacking tryptophan residue are
      required for hairpin resolution later in the reaction. We show that base flipping
      in Tn10 transposition is not a passive reaction in which a spontaneously flipped
      base is captured and retained by the protein. Rather, it is driven in part by a
      methionine probe residue that helps to force the flipped base from the base
      stack. Overall, it appears that base flipping in Tn10 transposition is similar to
      that in Tn5 transposition.

PMID- 19593449
TI  - Biogeography and virulence of Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is commonly carried asymptomatically in the
      human anterior nares and occasionally enters the bloodstream to cause invasive
      disease. Much of the global diversity of S. aureus remains uncharacterised, and
      is not clear how disease propensity varies between strains, and between host
      populations. METHODOLOGY: We compared 147 isolates recovered from five
      kindergartens in Chengdu, China, with 51 isolates contemporaneously recovered
      from cases of pediatric infection from the main hospital serving this community.
      The samples were characterised by MLST, the presence/absence of PVL, and
      antibiotic resistance profiling. PRINCIPAL FINDINGS: Genotype frequencies within
      individual kindergartens differ, but the sample recovered from cases of disease
      shows a general enrichment of certain MLST genotypes and PVL positive isolates.
      Genotypes under-represented in the disease sample tend to correspond to a single
      sequence cluster, and this cluster is more common in China than in other parts of
      the world. CONCLUSIONS/SIGNIFICANCE: Virulence propensity likely reflects a
      synergy between variation in the core genome (MLST) and accessory genome (PVL).
      By combining evidence form biogeography and virulence we demonstrate the
      existence of a "native" clade in West China which has lowered virulence,
      possibility due to acquired host immunity.

PMID- 19593450
TI  - Identification of global transcriptional dynamics.
AB  - BACKGROUND: One of the challenges in exploiting high throughput measurement
      techniques such as microarrays is the conversion of the vast amounts of data
      obtained into relevant knowledge. Of particular importance is the identification
      of the intrinsic response of a transcriptional experiment and the
      characterization of the underlying dynamics. METHODOLOGY AND FINDINGS: The
      proposed algorithm seeks to provide the researcher a summary as to various
      aspects relating to the dynamic progression of a biological system, rather than
      that of individual genes. The approach is based on the identification of smaller
      number of expression motifs that define the transcriptional state of the system
      which quantifies the deviation of the cellular response from a control state in
      the presence of an external perturbation. The approach is demonstrated with a
      number of data sets including a synthetic base case and four animal studies. The
      synthetic dataset will be used to establish the response of the algorithm on a
      "null" dataset, whereas the four different experimental datasets represent a
      spectrum of possible time course experiments in terms of the degree of
      perturbation associated with the experiment as well as representing a wide range
      of temporal sampling strategies. This wide range of experimental datasets will
      thus allow us to explore the performance of the proposed algorithm and determine
      its ability identify relevant information. CONCLUSIONS AND SIGNIFICANCE: In this
      work, we present a computational approach which operates on high throughput
      temporal gene expression data to assess the information content of the
      experiment, identify dynamic markers of important processes associated with the
      experimental perturbation, and summarize in a concise manner the evolution of the
      system over time with respect to the experimental perturbation.

PMID- 19593451
TI  - Decaying Raphia farinifera palm trees provide a source of sodium for wild
      chimpanzees in the Budongo Forest, Uganda.
AB  - For some years, chimpanzees have been observed eating the pith of decaying palm
      trees of Raphia farinifera in the Budongo Forest, Uganda. The reasons for doing
      this have until now been unknown. An analysis of the pith for mineral content
      showed high levels of sodium to be present in the samples. By contrast, lower
      levels were found in bark of other tree species, and also in leaf and fruit
      samples eaten by chimpanzees. The differences between the Raphia samples and the
      non-Raphia samples were highly significant (p<0.001). It is concluded that Raphia
      provides a rich and possibly essential source of sodium for the Budongo
      chimpanzees. Comparison of a chewed sample (wadge) of Raphia pith with a sample
      from the tree showed a clear reduction in sodium content in the chewed sample.
      Black and white colobus monkeys in Budongo Forest also feed on the pith of
      Raphia. At present, the survival of Raphia palms in Budongo Forest is threatened
      by the use of this tree by local tobacco farmers.

PMID- 19593452
TI  - Explaining lengths and shapes of yeast by scaling arguments.
AB  - Lengths and shapes are approached in different ways in different fields: they
      serve as a read-out for classifying genes or proteins in cell biology whereas
      they result from scaling arguments in condensed matter physics. Here, we propose
      a combined approach with examples illustrated for the fission yeast
      Schizosaccharomyces pombe.

PMID- 19593453
TI  - Molecular structure-property correlations from optical nonlinearity and thermal
      relaxation dynamics.
AB  - We apply ultrafast single beam Z-scan technique to measure saturation absorption
      coefficients and nonlinear-refraction coefficients of primary alcohols at 1560
      nm. The nonlinear effects result from vibronic transitions and cubic nonlinear
      refraction. To measure the pure total third-order nonlinear susceptibility, we
      removed thermal effects with a frequency optimized optical-chopper. Our
      measurements of thermal-relaxation dynamics of alcohols, from 1560 nm thermal
      lens pump and 780 nm probe experiments revealed faster and slower thermal
      relaxation timescales, respectively, from conduction and convection. The faster
      timescale accurately predicts thermal-diffusivity, which decreases linearly with
      alcohol chain-lengths since thermal-relaxation is slower in heavier molecules.
      The relation between thermal-diffusivity and alcohol chain-length confirms
      structure-property relationship.

PMID- 19593454
TI  - Modeling of the bacterial mechanism of methicillin-resistance by a systems
      biology approach.
AB  - BACKGROUND: A microorganism is a complex biological system able to preserve its
      functional features against external perturbations and the ability of the living
      systems to oppose to these external perturbations is defined "robustness". The
      antibiotic resistance, developed by different bacteria strains, is a clear
      example of robustness and of ability of the bacterial system to acquire a
      particular functional behaviour in response to environmental changes. In this
      work we have modeled the whole mechanism essential to the methicillin-resistance
      through a systems biology approach. The methicillin is a beta-lactamic antibiotic
      that act by inhibiting the penicillin-binding proteins (PBPs). These PBPs are
      involved in the synthesis of peptidoglycans, essential mesh-like polymers that
      surround cellular enzymes and are crucial for the bacterium survival.
      METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created
      using CellDesigner program and the data of molecular interactions are stored in
      Systems Biology Markup Language (SBML). To simulate the dynamic behaviour of this
      biochemical network, the kinetic equations were associated with each reaction.
      CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by
      methicillin, as well as the expression of PBP2a isoform, the regulation of the
      SCCmec elements (SCC: staphylococcal cassette chromosome) and the synthesis of
      peptidoglycan by PBP2a. The obtained results by our integrated approach show that
      the model describes correctly the whole phenomenon of the methicillin resistance
      and is able to respond to the external perturbations in the same way of the real
      cell. Therefore, this model can be useful to develop new therapeutic approaches
      for the methicillin control and to understand the general mechanism regarding the
      cellular resistance to some antibiotics.

PMID- 19593455
TI  - Mathematical Model of the Cupula-Endolymph System with Morphological Parameters
      for the Axolotl (Ambystoma tigrinum) Semicircular Canals.
AB  - By combining mathematical methods with the morphological analysis of the
      semicircular canals of the axolotl (Ambystoma tigrinum), a system of differential
      equations describing the mechanical coupling in the semicircular canals was
      obtained. The coefficients of this system have an explicit physiological meaning
      that allows for the introduction of morphological and dynamical parameters
      directly into the differential equations. The cupula of the semicircular canals
      was modeled both as a piston and as a membrane (diaphragm like), and the duct
      canals as toroids with two main regions: i) the semicircular canal duct and, ii)
      a larger diameter region corresponding to the ampulla and the utricle. The
      endolymph motion was described by the Navier-Stokes equations. The analysis of
      the model demonstrated that cupular behavior dynamics under periodic stimulation
      is equivalent in both the piston and the membrane cupular models, thus a general
      model in which the detailed cupular structure is not relevant was derived.

PMID- 19593456
TI  - Sensitivity Measures for Oscillating Systems: Application to Mammalian Circadian
      Gene Network.
AB  - Vital physiological behaviors exhibited daily by bacteria, plants, and animals
      are governed by endogenous oscillators called circadian clocks. The most salient
      feature of the circadian clock is its ability to change its internal time (phase)
      to match that of the external environment. The circadian clock, like many
      oscillators in nature, is regulated at the cellular level by a complex network of
      interacting components. As a complementary approach to traditional biological
      investigation, we utilize mathematical models and systems theoretic tools to
      elucidate these mechanisms. The models are systems of ordinary differential
      equations exhibiting stable limit cycle behavior. To study the robustness of
      circadian phase behavior, we use sensitivity analysis. As the standard set of
      sensitivity tools are not suitable for the study of phase behavior, we introduce
      a novel tool, the parametric impulse phase response curve (pIPRC).

PMID- 19593457
TI  - Race, Genes, and Justice: A Call to Reform the Presentation of Forensic DNA
      Evidence in Criminal Trials.

PMID- 19593469
TI  - A network-based method for predicting gene-nutrient interactions and its
      application to yeast amino-acid metabolism.
AB  - Cellular metabolism is highly dependent on environmental factors, such as
      nutrients, toxins and drugs, genetic factors, and interactions between the two.
      Previous experimental and computational studies of how environmental factors
      affect cellular metabolism were limited to the analysis of only a small set of
      growth media. In this study, we present a new computational method for predicting
      metabolic gene-nutrient interactions (GNI) that uncovers the dependence of gene
      essentiality on the presence or absence of nutrients in the growth medium. The
      method is based on constraint-based modeling, permitting the systematic
      exploration of a large putative growth media space. Applying this method to
      predict GNIs in the amino-acid metabolism system of yeast reveals complex
      interdependencies between amino-acid biosynthesis pathways. The predicted GNIs
      also enable the reverse-prediction of growth media composition, based on gene
      essentiality data. These results suggest that our approach may be applied to
      learn about the host environment in which a microorganism is embedded given data
      pertaining to gene lethality, providing a means for the identification of a
      species natural habitat.

PMID- 19593470
TI  - Energy based approach for understanding the recognition mechanism in protein
      protein complexes.
AB  - Protein-protein interactions play an essential role in the regulation of various
      cellular processes. Understanding the recognition mechanism of protein-protein
      complexes is a challenging task in molecular and computational biology. In this
      work, we have developed an energy based approach for identifying the binding
      sites and important residues for binding in protein-protein complexes. The new
      approach is different from the traditional distance based contacts in which the
      repulsive interactions are treated as binding sites as well as the contacts
      within a specific cutoff have been treated in the same way. We found that the
      residues and residue-pairs with charged and aromatic side chains are important
      for binding. These residues influence to form cation-, electrostatic and aromatic
      interactions. Our observation has been verified with the experimental binding
      specificity of protein-protein complexes and found good agreement with
      experiments. Based on these results we have proposed a novel mechanism for the
      recognition of protein-protein complexes: the charged and aromatic residues in
      receptor and ligand initiate recognition by making suitable interactions between
      them; the neighboring hydrophobic residues assist the stability of complex along
      with other hydrogen bonding partners by the polar residues. Further, the
      propensity of residues in the binding sites of receptors and ligands, atomic
      contributions and the influence on secondary structure will be discussed.

PMID- 19593471
TI  - Signaling network analysis of ubiquitin-mediated proteins suggests correlations
      between the 26S proteasome and tumor progression.
AB  - We performed a comprehensive analysis of a literature-mined human signaling
      network by integrating data on ubiquitin-mediated protein half-lives. We found
      that proteins with very long half-lives are connected to form a network backbone,
      while proteins with short and medium half-lives preferentially attach to the
      network backbone and scatter throughout the network. Furthermore, proteins with
      short and medium half-lives are mutually exclusive in network neighbors. Short
      half-life proteins are enriched in the upstream portion of the network,
      suggesting that ubiquitination might help initiate signal processing and
      specificity. We also discovered that ubiquitination preferentially occurs in
      positive regulatory loops. Furthermore, these loops predominately induce or
      positively regulate apoptosis, a major component in cancer signaling. These
      results lead us to discover that the highly expressed genes involved in the
      common machinery of ubiquitination, the 26S proteasome genes, are significantly
      correlated with tumor progression and metastasis. Furthermore, expression of the
      26S proteasome gene set predicts the clinical outcome of breast cancer patients.
      Our findings have implications for the development of cancer treatments and
      prognostic markers focused on the ubiquitination machinery.

PMID- 19593472
TI  - Relative stability of DNA as a generic criterion for promoter prediction: whole
      genome annotation of microbial genomes with varying nucleotide base composition.
AB  - The rapid increase in genome sequence information has necessitated the annotation
      of their functional elements, particularly those occurring in the non-coding
      regions, in the genomic context. Promoter region is the key regulatory region,
      which enables the gene to be transcribed or repressed, but it is difficult to
      determine experimentally. Hence an in silico identification of promoters is
      crucial in order to guide experimental work and to pin point the key region that
      controls the transcription initiation of a gene. In this analysis, we demonstrate
      that while the promoter regions are in general less stable than the flanking
      regions, their average free energy varies depending on the GC composition of the
      flanking genomic sequence. We have therefore obtained a set of free energy
      threshold values, for genomic DNA with varying GC content and used them as
      generic criteria for predicting promoter regions in several microbial genomes,
      using an in-house developed tool PromPredict. On applying it to predict promoter
      regions corresponding to the 1144 and 612 experimentally validated TSSs in E.
      coli (50.8% GC) and B. subtilis (43.5% GC) sensitivity of 99% and 95% and
      precision values of 58% and 60%, respectively, were achieved. For the limited
      data set of 81 TSSs available for M. tuberculosis (65.6% GC) a sensitivity of
      100% and precision of 49% was obtained.

PMID- 19593474
TI  - Strategies for efficient disruption of metabolism in Mycobacterium tuberculosis
      from network analysis.
AB  - Tuberculosis continues to be a major health challenge, warranting the need for
      newer strategies for therapeutic intervention and newer approaches to discover
      them. Here, we report the identification of efficient metabolism disruption
      strategies by analysis of a reactome network. Protein-protein dependencies at a
      genome scale are derived from the curated metabolic network, from which insights
      into the nature and extent of inter-protein and inter-pathway dependencies have
      been obtained. A functional distance matrix and a subsequent nearness index
      derived from this information, helps in understanding how the influence of a
      given protein can pervade to the metabolic network. Thus, the nearness index can
      be viewed as a metabolic disruptability index, which suggests possible strategies
      for achieving maximal metabolic disruption by inhibition of the least number of
      proteins. A greedy approach has been used to identify the most influential
      singleton, and its combination with the other most pervasive proteins to obtain
      highly influential pairs, triplets and quadruplets. The effect of deletion of
      these combinations on cellular metabolism has been studied by flux balance
      analysis. An obvious outcome of this study is a rational identification of drug
      targets, to efficiently bring down mycobacterial metabolism.

PMID- 19593473
TI  - Signal initiation in biological systems: the properties and detection of
      transient extracellular protein interactions.
AB  - Individual cells within biological systems frequently coordinate their functions
      through signals initiated by specific extracellular protein interactions
      involving receptors that bridge the cellular membrane. Due to their biochemical
      nature, these membrane-embedded receptor proteins are difficult to manipulate and
      their interactions are characterised by very weak binding strengths that cannot
      be detected using popular high throughput assays. This review will provide a
      general outline of the biochemical attributes of receptor proteins focussing in
      particular on the biophysical properties of their transient interactions. Methods
      that are able to detect these weak extracellular binding events and especially
      those that can be used for identifying novel interactions will be compared.
      Finally, I discuss the feasibility of constructing a complete and accurate
      extracellular protein interaction map, and the methods that are likely to be
      useful in achieving this goal.

PMID- 19593478
TI  - [Home-based enteral nutrition].

PMID- 19593479
TI  - N-3 fatty acids in glucose metabolism and insulin sensitivity.
AB  - Polyunsaturated fatty acids (PUFA) of the n-3 series are essential for normal
      growth and development. The health effects of these fatty acids include reduction
      of cardiovascular risk due to antiarrhythmic, antiinflammatory, anti-thrombotic
      and lipid lowering actions. An increase in unsaturation of the muscle membrane
      fatty acids is associated with improved insulin sensitivity. Higher proportion of
      n-3 fatty acids may have beneficial roles, such as antiobesity effects and
      protection against the metabolic syndrome and type 2 diabetes mellitus through a
      number of metabolic effects. However, controversy exists on the different effects
      of n-6 and n-3 polyunsaturated fatty acids as well as on the interacting effect
      of dietary saturated and monounsaturated fat. In addition, some adverse effects
      have been described concerning the use of fish oil supplements containing high
      doses of n-3 fatty acids. Several studies show Eskimos diabetes risk, while
      results of nutritional interventions on the influence of consuming diets rich in
      oily fish or other food rich in n-3 fatty acids is very limited. This article
      reviews the possible mechanisms through which n-3 PUFA are involved in glucose
      level control and insulin sensitivity. Intervention and epidemiological studies
      together with recent findings on the nutrigenomic field related with this subject
      are also briefly reviewed.

PMID- 19593480
TI  - Use of nutritional supplements in sports: risks, knowledge, and behavioural
      related factors.
AB  - A large number of recreational and elite athletes use nutritional supplements in
      hopes of improving performance. These aids can be costly and potentially harmful,
      and the advertised ergogenic gains are often based on little or no scientific
      evidence. Due to the lack of regulation of the dietary supplement industry, an
      abundance of supplement products of dubious value, content, and quality are now
      available around the world. Many supplement products contain substances that are
      prohibited in sport or that have been associated with significant morbidity and
      mortality. For athletes, lack of knowledge or misinformation has been established
      despite numerous sources of information being available, and the reasons for, and
      implications of, unsupervised and unrestricted supplement use require further
      attention. In addition to the necessity of an appropriate regulation of dietary
      supplements, nutritional education and scientifically sound guidance for athletes
      is required. Intervention and prevention efforts should be particularly targeted
      to adolescents.

PMID- 19593481
TI  - [Management models in clinical nutrition: weaknesses and strengths].
AB  - At the 6th Abbott-SENPE Debate Forum a multidisciplinary and multiprofessional
      discussion was established in order to seek for the model or the models of
      clinical management most appropriate for Clinical Nutrition and Dietetics Units
      (CNAD) in Spain. The weaknesses and strengths as well as opportunities for the
      current systems were assessed concluding that a certain degree of disparity was
      observed not only due to regional differences but also to different hospital
      types. It was proposed, from SENPE, the creation of a working group helping to
      standardize the models and promote the culture of Integral Control and Change
      Management.

PMID- 19593482
TI  - [Intragastric balloon in obesity treatment].
AB  - Obesity is considered a chronic and epidemic illness, hece difficult to treat. As
      conservative treatment has a high rate of failure, and considering morbimortality
      and sequels of surgery, less invasive techniques appeared to contribute to the
      treatment of this illness. The most implanted technique nowadays is the
      Intragastric Balloon, considered more efficient as conservative treatments and
      with less risks tan surgery, but having today a lack of consensus on indications
      and few information on his limitations, while its apparition in medias promote an
      important expansion in the 4 last years. In this publication, we do a critical
      revision, and describe limitations of this treatment, based on the evidences
      given by literature. We conclude this revision with some recommendations
      concerning the technique and indications, material and human requiring, need of a
      Multidisciplinary Team, as well as an adequate control and following.

PMID- 19593483
TI  - Life-style factors associated with overweight and obesity among Spanish adults.
AB  - OBJECTIVES: To assess the relationship between life styles and eating habits with
      the overweight and obesity prevalence in a Spanish adult population. METHODS: A
      population-based, cross-sectional study conducted on 2640 subjects older than 15
      years, in Cadiz (Spain). Surveys were conducted in subjects' homes to obtain life
      styles, eating habits, and anthropometric data. Logistic regression has been used
      to study the association between the life style variables and overweight and
      obesity. RESULTS: Prevalence of overweight and obesity in Cadiz is 37% and 17%,
      respectively; higher in males and increases with age. BMI has an inverse
      relationship with educational level (PR = 2.3, 1.57-2.38). The highest levels of
      obesity are associated with daily alcohol consumption (PR = 1.39, 1.29-1.50),
      greater consumption of television,and sedentary pursuit (PR 1.5, 1.07-1.24). A
      lower prevalence of obesity is observed among those with active physical activity
      (10.9% vs 21.6%), with differences between sex. Following a slimming diet is more
      frequent in the obese and in women but dedicate more hours than men to passive
      activities. In men is greater the consumption of alcohol, high energy foods and
      snacks. Overweight and obesity is associated with the male sex (OR = 3.35 2.75
      4.07), high consumption of alcohol (OR = 1.38 1.03-1.86) and watching television
      (OR = 1.52 1.11-2.07), and foods likes bread and cereals (OR = 1.47 1.13-1.91).
      Exercise activities is a protective factor (OR = 0.76 0.63-0.98). CONCLUSIONS:
      Life styles factors associated with overweight and obesity present different
      patterns in men and women and is necessary to understand them to identify areas
      for behavioural intervention in overweight and obesity patients.

PMID- 19593484
TI  - [Micronutrients in parenteral nutrition].
AB  - At a multidisciplinary debate, and after reviewing the evidence available as well
      as experts' opinion, the IV Baxter-SENPE Working Panel established the
      indications and managemente guidelines for micronutrients (water-soluble and fat
      soluble vitamins, and oligoelements or trace elements) in parenteral nutrition.
      It was concluded about the convenience of daily intake of micronutrients with
      diferent options regarding deficiente or excessive dosages, administration
      systems, interactions, monitoring, and cots-effectiveness.

PMID- 19593485
TI  - [Karnosfsky index as a mortality predicting factor in patients on home-based
      enteral nutrition].
AB  - Karnofsky Index (KI) is a widely used functional scale developed for oncology
      patients. It has proved useful as outcome predictor with cancer and geriatric
      patients. Theoretically, KI could be used to predict mortality in patients with
      home enteral nutrition (HEN). STUDY OBJECTIVES: To determine baseline KI and its
      6-month evolution in HEN patients, and to assess its relation with the mortality
      rate. METHODOLOGY: Observational and prospective study carried out during 2002
      and 2003 with tube feeding neurologic and cancer patients followed during 10
      months since their HEN programme inclusion. RESULTS: 201 patients were included,
      131 (65.2%) with neurological diseases and 70 (34.8%) with neoplasm. There were
      not significant differences between groups in age, days with HEN and mortality
      rate at the end of the study period (35.1% in neurologic patients and 40% in
      cancer ones). 27.1% of cancer patients had resumed full oral nutrition after ten
      months from the beginning of the study, whereas only 10.7% of neurologic patients
      did (p < 0.05). In the three measurement phases (initial, past-3 and past-6
      months) KI values were higher for cancer patients than for neurologic ones (p <
      0.001). In both groups we didn't found statistically significant differences in
      KI along the three measurements. A significant relation was observed overall
      between initial KI values and average survival after 10 months (p < 0.001), and
      an inverse relation was found between the former and mortality rate (p < 0.001).
      CONCLUSION: KI is a useful tool to predict mortality rate in cancer and
      neurologic patients under HEN.

PMID- 19593486
TI  - [Rate of undernutrition and response to specific nutritional therapy in Crohn's
      disease].
AB  - OBJECTIVES: to determine the rate of malnutrition in patients with Crohn's
      disease in our area (Substudy A). We assess in long-term the response of
      malnourished patients to treatment of nutritional supplement with TGF-beta2
      (Substudy B). SUBJECTS: ninety-eight (51% females) patients with Crohn's disease
      without selection, ages: 39.2 +/- 15.19 years, range: 18-81 years were included
      in Substudy A. In Substudy B thirty-nine malnourished patients (52% females) were
      included with an average age of 36.41 +/- 5.2 years and range: 19-45 (Substudy
      B). METHODS: the design of the Substudy A was an observational and cross
      sectional study. Whereas, the Substudy B was a longitudinal, open intervention
      study with active (historical) control. The variables were anthropometric
      parameters, electrical bioimpedance, biochemical measures, index of disease
      activity, subjective global assessment and the kind of treatment that every
      patient has received. MAIN RESULTS: the malnutrition rate was 52%, being the most
      frequent the caloric malnutrition, followed by mixed malnutrition. Thirty four
      per cent of the patients had iron deficiency. Twelve months of nutritional
      therapy with supplement specifically enriched in TGF-beta2 improved the evolution
      of the disease determined by a decrease in CDAI. CONCLUSIONS: The rate of
      malnutrition was similar to that of previous studies realized in Spain. Our study
      confirms the high rate of iron deficiency that the patients suffer with Crohn's
      disease. The response to the treatment is favorable, especially regarding the
      natural history of the disease.

PMID- 19593487
TI  - [Cardiovascular risk and metabolic syndrome at the Toledo Area Study].
AB  - OBJECTIVES: To know the anthropometric and clinical characteristics of a children
      population sample, to study the prevalence and concurrence of cardiovascular risk
      factors in that sample, and to define the prevalence of metabolic syndrome in
      that population considering the blood pressure, HDL cholesterol, and fasting
      glycemia values, as well as the anthropometrical measurements. SETTING: The
      health care area of Toledo. SUBJECTS: Children aged 4 years included in the
      Toledo Area Study. INTERVENTIONS: A prospective study is performed on the
      metabolic syndrome-related cardiovascular risk factors in a sample of 58 children
      from the Toledo Area Study. Data on anthropometrical and lipoprotein profile at
      birth were obtained. The anthropometrical, lipoprotein, and biochemical data were
      compared with those from other populations; we also looked for possible
      differences between boys and girls. At the same time, we analyzed the association
      between several cardiovascular risk factors in that population (logistic
      regression model) and we set up the cut-off levels to define in the children
      population possible candidates to metabolic syndrome. These levels are in
      agreement with those from similar adolescent populations. RESULTS: Among the risk
      factors, higher systolic and diastolic pressure values stand up in girls (93.93 
      boys- vs 98.41 -girls- p = 0.058; 52.32 -boys- vs 57.27 -girls- p = 0.026,
      respectively), as well as the concurrence of high blood pressure and
      hypercholesterolemia in boys (almost 7%). The whole prevalence of candidates to
      MS was 10.9% (5 girls -9.1%- and 1 boy -1.8%-). A high percentage of boys (< 50%)
      presented a wrong diet from the perspective of dietary cardiovascular risk
      markers. The only statistically significant variable at 10% (p < 0.10) in the
      regression model was Apo AI. CONCLUSIONS: It is relevant that the presence of MS
      is higher in girls and in those infants with a dyslipemic nonhypercholesterolemic
      profile at birth, which emphasizes the usefulness of cardiovascular risk factors
      prospection from early ages.

PMID- 19593488
TI  - [A pilot study on a quality improvement plan with systematic nutritional
      screening in patients admitted to a regional hospital].
AB  - OBJECTIVE: A pilot study to assess the feasibility of implementing a hospital
      protocol for systematic nutritional screening of admitted patients. METHOD:
      Descriptive cross-sectional study. Patients admitted to the Orthopedic Surgery
      Department of the Regional Hospital of Alcaniz were systematically included
      within the first 48 hours of hospitalization, from February to September of 2007.
      The screening methods used were the Nutritional Risk Index (NRI), the CONUT
      Nutritional Control system, and an indicator based on SENPE recommendations. The
      need for nutritional support was defined as the presence of any of the following
      instances: moderate to severe hyponutrition according to the NRI or CONUT
      methods, or hyponutrition according to the adapted SENPE recommendations.
      RESULTS: 36.4% of the patients assessed need nutritional support. The rate of
      hyponutrition according to CONUT is 13.6%, by SENPE criteria is 27.3%, and by the
      NRI 29.5%. The inter-method agreement is statistically significant and clinically
      acceptable: Kappa between NRI and CONUT 0.547, between NRI and SENPE 0.609, and
      between CONUT and SENPE 0.593. CONCLUSIONS: The implementation of a structured
      protocol for collecting the anthropometrical and biochemical parameters
      implicating a multidisciplinary hospital team enables identifying those patients
      in whom appropriate nutritional support may improve their prognosis during
      hospital stay.

PMID- 19593489
TI  - [Impact of family support over food intake and depressive status in cervical
      cancer patients during hospitalization].
AB  - INTRODUCTION: Uterine cervical cancer represents a public health problem in
      Mexico; the patients suffer physical and psychological stress leading to
      depression and weight loss. Eating with a relative has positive effects in food
      ingestion and depressive status in hospitalized patients. In our society, food is
      the closest way that family members have to bring care and to show affection to
      the patient that has less appetite as disease goes on. OBJECTIVE: To establish
      the relationship between presence of the family during the meals and depresion,
      food intake, and weight variation during hospitalization. METHODOLOGY: 106 women
      admitted to the Oncology Department at the General Hospital of Mexico with a
      diagnosis of CUCA clinical stage II and III were studied in order to improve
      their condition. Weight and height, diet by means of 24 hour recalls were
      assessed both at hospital admission and discharge, and Beck's depression
      inventory was applied; the frequency with which the relatives escorted the
      patient was recorded. RESULTS: Patients were classified in two groups according
      to the frequency of family escorting; it was found that 43 patients (40.6%) were
      accompanied, and 63 patients (59.4%) were not. We did not find significant
      differences in age and days of hospital stay between the groups (p > 0.05). The
      escorted patients had more foods available during hospitalization (p < 0.05).
      Energy consumption (kcal) in escorted patients was higher by 12.7% as compared to
      non-escorted patients. 76.7% of the escorted patients were depressed, as compared
      to 55% in the non-escorted group. Significant differences were found with regards
      to clinical status and presence of depression (p < 0.05) between the study
      groups. CONCLUSIONS: Family escorting does not have an influence on the amount of
      foods consumed during hospitalization or body weight variation; however, it does
      have an influence on the presence of depression.

PMID- 19593490
TI  - [Obesity and insulin resistance among adolescents from Chiapas].
AB  - OBJECTIVE: The aim of this study was to assess the association of overweight and
      obesity with insulin resistance, hypertension, and hyperlipidemic among 12 to 15
      year olds from private and public schools in Chiapas. METHODS: This was a cross
      sectional study with a random selection of 259, 12 to 15 year old teenagers from
      private and public middle schools. Conventional methods were used to measure body
      weight, height and blood pressure. After a 14-hour fasting period, a blood sample
      was taken for glucose, total lipids, total cholesterol, LDL-cholesterol,
      triglycerides and insulin levels. HDL-cholesterol and HOMA-IR were estimated.
      Weight-for-age, height-for-age and BMI-for-age were calculated using the CDC
      tables for growth. To assess the difference between overweight and obesity by
      gender and type of school a X2 and t-test was performed in order to evaluate the
      mean difference between biochemical indicators of normal and overweight
      adolescents. The Mann-Whitney test was conducted to assess differences in blood
      pressure. RESULTS: Observations included high prevalence of overweight (19%) and
      obesity (13%) with no difference between type of school, gender, or group of age
      (Table 2). High prevalence of hipercholesterolemia (26%), LDLcholesterol (7%),
      HDL hypolipoproteinemia (3%), triglycerides (10%), systolic blood pressure (6%),
      and metabolic syndrome (1.6%) were also observed. The BMI was associated to total
      lipid, total cholesterol, insulin, and HOMA-IR levels. The Overweight and obese
      had higher levels of insulin, HOMA-IR, triglycerides, and blood pressure and
      lower levels of HDL-cholesterol.

PMID- 19593491
TI  - [Assessment of the diet of school children from Granada and influence of social
      factors].
AB  - INTRODUCTION: To perform a balanced diet adapted to the needs of the different
      life stages is important for a correct peopleis physical and psychological
      growth, preventing disease, and obtaining an optimal health status. The
      industrialized society is characterized by unbalanced energy balance due to an
      increase of energy intake through foods and decreased energy waste with increased
      SFA consumption. OBJECTIVE: To assess average dietary intake and how certain
      demographical and socio-economic factors have an influence on dietary habits of a
      sample of schoolchildren from Granada city. METHODS: The study population
      comprises 3,190 children and adolescents schooled at Granada city, with ages
      comprised between 8 and 15 years. A previously validated specific questionnaire
      was created including lifestyle habits, dietary habits, 24-hour recall, and
      frequency of foods consumption. RESULTS AND DISCUSSION: The average caloric
      ingestion in this population is higher than the predicted average waste
      recommended by WHO, with higher energy values being found in males. The caloric
      profile found in our sample is clearly unbalanced. The main protein sources were
      meats and dairy products. There were high intakes of SFA, PUFA, and cholesterol,
      markedly surpassing the recommended values. Vitamin E intake did not reach the
      daily recommended values. With regards to dietary habits, the study population
      spends less than 30 minutes for breakfast and about half an hour for lunch and
      dinner, those spending more time for meals having the highest energy and proteins
      intake.

PMID- 19593492
TI  - [Quality of the diet of a population of young people of Guadalajara].
AB  - INTRODUCTION: The population of Guadalajara traditionally has consumed a
      Mediterranean diet with the typical variations of the central zone of the
      peninsula, but the acquisition of erroneous habits of life they can be
      translated, specially in the young people, in a not healthful nourishing
      conducts. OBJECTIVE: To evaluate the quality of the diet, by means of an index of
      healthy nourishment (IAS) and percentage of adhesion to the Mediterranean diet (%
      ADM), of a teen population (n = 467) and their relation with different
      physiological parameters and sociodemograficos. METHOD: A nutritional study has
      been realized on the quality of the diet in a teen population of Guadalajara of
      467 young people (12-17 years) by means of questionnaires of frequency of
      consumption of seven days. Likewise, there has determined the ingestion of
      nutrients and the index of healthy nourishment (IAS) using the program of
      nutrition DIAL(c). RESULTS: The results show that the average of the population
      takes a diet with an acceptable IAS (62.78), though with trend towards low
      qualities, with high ingestions of saturated fats (38.90 +/- 6.58 g), cholesterol
      (384.69 +/- 74.24 mg) and sodium (3,395.43 +/-729.57 mg). Respect to % MDA there
      has been obtained an average value of 42.86 +/- 15.52%. These values differ
      depending on the age (improves with the age), the sex (better quality of the diet
      consumed by the girls). Likewise, all the factors sociodemograficos and the way
      of life considered, they influence the quality indicators used.

PMID- 19593493
TI  - Birth weight variation according to maternal characteristics and gestational
      weight gain in Brazilian women.
AB  - OBJECTIVES: This study aims to identify birth weight variation according to
      maternal characteristics and gestational weight gain. METHODS: It is a cross
      sectional descriptive study with 433 puerperal women (> or = 20 years old) who
      attended a public maternity hospital in Rio de Janeiro. The data were collected
      through interviews with the women and access to their medical records. Several
      models were tested using linear regression, using the stepwise method to identify
      the predictive variables of birth weight. RESULTS: The mean maternal age and
      gestational age at the end of pregnancy were 27 years old (+/- 5.09 years) and 39
      weeks (+ 1.68 weeks), respectively. The data shows that the mean number of
      prenatal and nutritional prenatal care appointments were 8.24 (+/- 2.98) and 2.26
      (+/- 2.33), respectively. Among the predictor variables of birth weight, total
      gestational weight gain (beta = 25.29; p = 0.000), pre-gestational BMI (beta
      =13.02; p = 0.037), and the number of pre-natal care appointments (beta = 28.21;
      p = 0.007) were highlighted. The association of weight gain in the three
      trimesters was also verified. CONCLUSIONS: This study confirms the interface
      between adequacy of the pre-gestational and gestational nutritional status and
      some maternal characteristics with birth weight. Nutritional care should be
      recognised as part of the actions during pre-natal assistance.

PMID- 19593494
TI  - [Prevalence and duration of breast-feeding: its influences on the weight and the
      morbidity].
AB  - OBJECTIVE: To estimate the prevalence and the average length of Lactation. To
      describe the development of the weight during the first year of life and the
      demand of paediatric consultations in relation to the type of lactation. METHODS:
      A cross-sectional study was done using retrospective data. There was gathered a
      random sample of clinical histories of born children between years 2000 and 2005.
      There was estimated the prevalence of breast-feeding from the beginning until
      three and six months. An index of global desertion was elaborated. The average
      weight and the number of paediatric consultations were related to the type of
      lactation. RESULTS: The children initiate exclusive breastfeeding (MEL) in a
      63.5% (CI 95%: 58.6-64.5). 22.6% amount them (IC 95%: 18.4-26.9) remained it
      until six months age. After three months of MEL 43.4% of the subjects gave up
      exclusively lactation. At the age of six months only 33.6% remained with MEL.
      Mixed form of lactation (MTL) was kept in 80.5% of the subjects (IC 95%: 75.4
      84.6). Children included in the program of MTL (exclusive or mixed) have a minor
      index of desertion (26.5% and 54.4% up to three and six months, respectively). A
      higher weight was detected in children with mixed lactation. Those on the MEL up
      to six months consulted the paediatrician 4.5 times a year, whereas children with
      artificial lactation did it 6.5 times during their first year of life. There were
      statistically significant differences found (p < 0.007). CONCLUSIONS: Percentage
      of lactation in the group studied is far from recommended levels (WHO). Exclusive
      breastfeeding (MEL) entails a suitable weight development, as well as a minor
      morbidity in the first year of life.

PMID- 19593495
TI  - [Evolution of home-based enteral nutrition in Madrid 2002-2007].
AB  - INTRODUCTION: Home-based enteral nutrition in Madrid uses the official
      prescription form which facilitates the use of information systems for analyzing
      consumption and evolution. OBJECTIVES: Qualitative and quantitative analysis of
      the evolution of HBEN use from 2002 to 2007. Trend and identification of the
      products with higher impact for the period 2006-2007. Patient's characteristics.
      METHODS: Selection of invoiced prescriptions of HBEN products, classification by
      type, and analysis of price and pack number evolution for the period 2002 -2007.
      Study of the consumption evolution 2006-2007 identifying those products with
      higher impact, the prescription distribution, and the characteristics of the
      patients in whom HBEN is prescribed. RESULTS: In the period 2002-2007, the number
      of packs has increased more than twice and the costs have tripled, observing a
      shift towards complete hyperproteinic diets. When analyzing these diets in the
      period 2006-2007, there are five products that have increased the number of packs
      by more than 210%. The mean patientsi age was 60.33 years. The most frequent
      diagnoses were oncologic and neurologic. 69% of the treatments are prescribed as
      dietary supplements for an ordinary diet. DISCUSSION: For the last 6 years, an
      increasing trend is observed as well as a shift towards complete hyperproteinic
      diets, which in 2007 accounted for almost a third of the whole consumption. Two
      thirds of the therapies are focused on geriatric patients with oncologic or
      central nervous system degenerative pathologies.

PMID- 19593497
TI  - [Assessment of nutritional status in a Mexican population of adult patients with
      rheumatoid arthritis].
AB  - BACKGROUND: Rheumatoid arthritis (RA) represents a life-long chronic inflammatory
      process frequently associated to potential multiorganic complications.
      Cardiovascular diseases and nutritional alterations are increased in AR
      populations and represent potential factors that alter negatively the disease
      course and prognosis. PURPOSE: To evaluate nutritional status from a Mexican AR
      population, including body composition, anthropometrics and dietary patterns.
      MATERIAL AND METHODS: There were included 100 RA outpatients from a regional
      rheumatic centre located in San Luis Potosi Mexico. Nutritional assessment
      included anthropometric evaluation, bioelectrical impedance analysis (BIA) and
      dietary patterns evaluation. RESULTS: 100 RA out-patients were included. Mean age
      was 47.6 +/- 13.3 years, with a mean disease course of 10.18 +/- 9.02. 79% of
      patients were in RA functional class II and 21% in class III. Average body mass
      index 26.8 +/- 4.4 kg/m2 According to body mass index categories, 65% patients
      were within the range of overweight and obesity and 2% of patients were
      undernourished. Mean waist circumference 86.7 +/- 11.1 cm, 34% of patients showed
      waist circumference values over the limits established for the definition of
      metabolic syndrome. Lean body mass was diminished in 48% patients. Body fat mass
      estimated by anthropometry and BIA was increased in 94 patients (94%). DIETARY
      PARAMETERS: Mean energy intake was 26.4 +/- 8.2 kcal/kg. There was qualitative
      nutritional inadequacy in 90 patients (90%). Protein intake was optimal in all
      the patients. CONCLUSION: Nutritional alterations are highly prevalent in Mexican
      RA population; our study showed freefat mass depletion, low caloric intake,
      dietary inadequate parameters and fat mass increments as the more prevalent
      findings. Nutritional assessment and nutritional strategies are recommended as
      potential measures to improve RA clinical course and prognosis.

PMID- 19593496
TI  - Preliminary evidence of physical activity levels measured by accelerometer in
      Spanish adolescents: the AFINOS Study.
AB  - BACKGROUND: It is necessary to know the levels of physical activity (PA) for a
      better understanding of the development of chronic diseases in youth. The aim of
      this study was to assess levels of total PA and time spent in different
      PAintensities in Spanish adolescents by accelerometer. METHODS: A sub-sample of
      214 healthy Spanish adolescents (107 females), aged 13-16 years, enrolled in the
      AFINOS Study was selected for this study. Participants wore the ActiGraph GT1M
      accelerometer for 7 consecutive days. Total PA and time spent in sedentary,
      light, moderate, vigorous, and moderate to vigorous physical activity (MVPA) was
      estimated using the accelerometer. Adiposity was measured in the sample using sum
      of 6 skinfoldthickness, waist circumference and BMI. RESULTS: Adolescent boys
      were engaged in higher levels of total PA, moderate PA, vigorous PA and MVPA than
      adolescent girls, whereas girls were engaged in higher levels of light PA.
      Differences between age groups showed that the 15-16 years group did more total
      PA (P = 0.008) than the 13-14 years group. Adolescents with highest levels of
      body fat were less active and spent less time in vigorous PA and MVPA than
      adolescents with less body fat. Among the current sample, 71.1% of the
      adolescents (82.2% adolescent boys and 60.7% adolescent girls) reached the
      recommendation of > or = 60 min in MVPA. CONCLUSIONS: Although these findings
      suggest that Spanish adolescents have similar PA levels than other European
      adolescents, further cross-sectional and longitudinal studies must assess PA
      levels in free-living conditions in Spanish children and adolescents using
      objective methods such as accelerometers, heart rate monitors and pedometers.

PMID- 19593498
TI  - [Visibility of the Latin-American scientific production on nutrition: the
      importance of the key words].

PMID- 19593499
TI  - Serum transferrin and serum prealbumin as markers of response to nutritional
      support in patients with esophageal cancer.

PMID- 19593502
TI  - History of adjuvant therapy.

PMID- 19593503
TI  - Prognostic and predictive factors.

PMID- 19593504
TI  - New perspectives for therapy choice.

PMID- 19593505
TI  - Pathology role in adjuvant setting.

PMID- 19593506
TI  - Guidelines, consensus conferences and overviews (meta-analysis).

PMID- 19593507
TI  - Statistical issues and challenges.

PMID- 19593508
TI  - Multidisciplinary care: optimising team performance.

PMID- 19593509
TI  - Preoperative chemo- and endocrine therapy.

PMID- 19593510
TI  - Adjuvant chemotherapy.

PMID- 19593511
TI  - Postoperative endocrine therapy for invasive breast cancer.

PMID- 19593512
TI  - Adjuvant therapy of breast cancer - bisphosphonates.

PMID- 19593513
TI  - Trastuzumab.

PMID- 19593514
TI  - Lapatinib: new directions in HER2 directed therapy for early stage breast cancer.

PMID- 19593515
TI  - Supportive care during adjuvant treatment.

PMID- 19593516
TI  - Dose in (adjuvant) chemotherapy of breast cancer.

PMID- 19593517
TI  - Timing of adjuvant therapy.

PMID- 19593518
TI  - Sequencing of systemic treatment and radiotherapy.

PMID- 19593519
TI  - Young patients with breast cancer.

PMID- 19593520
TI  - Special populations: elderly patients.

PMID- 19593521
TI  - Adjuvant therapy in patients with breast cancer during pregnancy.

PMID- 19593522
TI  - Investigations after adjuvant therapy.

PMID- 19593523
TI  - Quality of life issues during adjuvant endocrine therapy.

PMID- 19593524
TI  - Fertility.

PMID- 19593525
TI  - Cognitive function in breast cancer survivors.

PMID- 19593527
TI  - Social issues: marital support.

PMID- 19593526
TI  - Costs of adjuvant breast cancer treatments.

PMID- 19593528
TI  - The view and role of breast cancer advocacy.

PMID- 19593529
TI  - The voice of a special patient.

PMID- 19593535
TI  - [Influenza pandemic: Would healthcare workers come to work? An analysis of the
      ability and willingness to report to duty].
AB  - In the event of an influenza pandemic, the workload of healthcare workers (HCWs)
      would raise dramatically. Moreover, due to the nature of this occupation, one's
      own risk of infection is also increased. Given this background, the question
      arises as to whether HCWs would actually report to work during an influenza
      pandemic. To answer this question an anonymous and voluntary questionnaire was
      distributed to HCWs of a German university hospital during the seasonal influenza
      vaccination. In total, 36.2% of respondents declared that, in the event of a
      potential influenza pandemic, they would not go to work. The provision of
      adequate personal protective equipment, such as masks (88.2%), was highlighted as
      an important precautionary measure. The confidence of employees in public policy,
      the public health system, and in employers was, altogether, judged to be
      insufficient; public policy received the worst results in this respect. Pandemic
      preparedness plans should consider both the proportion of ill employees, as well
      as the proportion of employees who may be absent due to personal fears or private
      responsibilities. Appropriate protective measures should be clarified and
      communicated in the prepandemic phase. Initiatives to strengthen workers'
      confidence in the fact that everything would be done to protect them against
      becoming ill in the event of a pandemic also need to be implemented.

PMID- 19593536
TI  - [The relationship between German university hospitals and medical schools.
      Cooperation model versus integration model].
AB  - The relationship between German university hospitals and medical schools is
      mainly based on the cooperation model; in a few cases the integration model is
      applied. Both models bear characteristic advantages and disadvantages; in the
      cooperation model, e.g., processes might be slowed down by a multitude of
      regulatory mechanisms. The integration model supports a close connection of the
      medical school and university hospital. Currently, legislation concerning
      university medicine in Germany shows a trend to increase the influence of the
      government and the university president within the balance of power. Therefore,
      the cooperation model is still favored. In order that university hospitals remain
      sustainable for the future, especially in terms of research, site-specific
      solutions have to be developed and legitimated.

PMID- 19593537
TI  - [Medical education in the dilemma between theory and praxis. The reforms in
      medical studies make an impact].
AB  - The 2002 German medical licensing regulations for physicians represent an interim
      end point of a development that demands stronger orientation of medical education
      towards practical skills training. Meanwhile the responsible institutions have
      implemented the regulations. The article portrays the history of this reform of
      medical studies and critically discusses the value of an early practical
      orientation during the course of medical education. The article stresses the
      value of medical knowledge, which must receive priority in order to sustain the
      high quality of medical practice.

PMID- 19593531
TI  - A small GTPase, human Rab32, is required for the formation of autophagic vacuoles
      under basal conditions.
AB  - Here we show that a small GTPase, Rab32, is a novel protein required for the
      formation of autophagic vacuoles. We found that the wild-type or GTP-bound form
      of human Rab32 expressed in HeLa and COS cells is predominantly localized to the
      endoplasmic reticulum (ER), and overexpression induces the formation of
      autophagic vacuoles containing an autophagosome marker protein LC3, the ER
      resident protein calnexin and endosomal/lysosomal membrane protein LAMP-2, even
      under nutrient-rich conditions. The recruitment of Rab32 to the ER membrane was
      necessary for autophagic vacuole formation, suggesting involvement of the ER as a
      source of autophagosome membranes. In contrast, the expression of the inactive
      form of, or siRNA-specific for, Rab32 caused the formation of p62/SQSTM1 and
      ubiquitinated protein-accumulating aggresome-like structures and significantly
      prevented constitutive autophagy. We postulate that Rab32 facilitates the
      formation of autophagic vacuoles whose membranes are derived from the ER and
      regulates the clearance of aggregated proteins by autophagy.

PMID- 19593538
TI  - [The German University Medicine Map].
AB  - The University Medicine Map is a major step towards the realization of more
      transparency regarding the overall services of the medical schools in research,
      teaching, and patient care within the German university system. It includes
      comparative information about all 36 medical schools in Germany for the following
      areas: legal framework, finance, personnel, medical research, teaching and
      medical education, as well as patient care. The complete set of data for this map
      is accessible online under www.landkarte-hochschulmedizin.de and a selection of
      data is also available in print. Advantages and possible political implications
      for the higher education sector as well as the public domain are illustrated.
      Finally, the perspectives for future developments are indicated.

PMID- 19593530
TI  - Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and
      pathology.
AB  - The small heat shock protein Hsp27 or its murine homologue Hsp25 acts as an ATP
      independent chaperone in protein folding, but is also implicated in architecture
      of the cytoskeleton, cell migration, metabolism, cell survival,
      growth/differentiation, mRNA stabilization, and tumor progression. A variety of
      stimuli induce phosphorylation of serine residues 15, 78, and 82 in Hsp27 and
      serines 15 and 86 in Hsp25. This post-translational modification affects some of
      the cellular functions of Hsp25/27. As a consequence of the functional importance
      of Hsp25/27 phosphorylation, aberrant Hsp27 phosphorylation has been linked to
      several clinical conditions. This review focuses on the different Hsp25/27
      kinases and phosphatases that regulate the phosphorylation pattern of Hsp25/27,
      and discusses the recent findings of the biological implications of these
      phosphorylation events in physiological and pathological processes. Novel
      therapeutic strategies aimed at restoring anomalous Hsp27 phosphorylation in
      human diseases will be presented.

PMID- 19593539
TI  - How do animals use substrate-borne vibrations as an information source?
AB  - Animal communication is a dynamic field that promotes cross-disciplinary study of
      the complex mechanisms of sending and receiving signals, the neurobiology of
      signal detection and processing, and the behaviors of animals creating and
      responding to encoded messages. Alongside visual signals, songs, or pheromones
      exists another major communication channel that has been rather neglected until
      recent decades: substrate-borne vibration. Vibrations carried in the substrate
      are considered to provide a very old and apparently ubiquitous communication
      channel that is used alone or in combination with other information channels in
      multimodal signaling. The substrate could be 'the ground', or a plant leaf or
      stem, or the surface of water, or a spider's web, or a honeybee's honeycomb.
      Animals moving on these substrates typically create incidental vibrations that
      can alert others to their presence. They also may use behaviors to create
      vibrational waves that are employed in the contexts of mate location and
      identification, courtship and mating, maternal care and sibling interactions,
      predation, predator avoidance, foraging, and general recruitment of family
      members to work. In fact, animals use substrate-borne vibrations to signal in the
      same contexts that they use vision, hearing, touch, taste, or smell. Study of
      vibrational communication across animal taxa provides more than just a more
      complete story. Communication through substrate-borne vibration has its own
      constraints and opportunities not found in other signaling modalities. Here, I
      review the state of our understanding of information acquisition via substrate
      borne vibrations with special attention to the most recent literature.

PMID- 19593540
TI  - Comparison of the starch synthesis genes between maize and rice: copies,
      chromosome location and expression divergence.
AB  - Gene duplication and divergence are important evolutionary processes. It has been
      suggested that a whole genome duplication (WGD) event occurred in the Gramineae,
      predating its divergence, and a second WGD occurred in maize during its
      evolution. In this study we compared the fate of the genes involved in the core
      pathway of starch biosynthesis following the ancient and second WGDs in maize and
      rice. In total, thirty starch synthesis genes were detected in the maize genome,
      which covered all the starch synthesis gene families encoded by 27 genes in rice.
      All of these genes, except ZmGBSSIIb and ZmBEIII, are anchored within large-scale
      synteny blocks of rice and maize chromosomes. Previous findings and our results
      indicate that two of the current copies of many starch synthesis genes (including
      AGPL, AGPS, GBSS, SSII, SSIII, and BEII) probably arose from the ancient WGD in
      the Gramineae and are still present in the maize and rice genome. Furthermore,
      two copies of at least six genes (AGPS1, SSIIb, SSIIIb, GBSSII, BEI, and ISA3)
      appear to have been retained in the maize genome after its second WGD, although
      complete coding regions were only detected among the duplicate sets of AGPS1,
      SSIIb, and SSIIIb. The expression patterns of the remaining duplicate sets of
      starch synthesis genes (AGPL1/2, AGPS1/2, SSIIa/b, SSIIIa/b, GBSSI/II, and
      BEIIa/b) differ in their expression and could be classified into two groups in
      maize. The first group is mainly expressed in the endosperm, whereas the second
      is expressed in other organs and the early endosperm development. The four
      duplicate sets of ZmGBSSII, ZmSSIIb, ZmSSIIIb and AGPS1, which arose from the
      second WGD diverged in gene structure and/or expression patterns in maize. These
      results indicated that some duplicated starch synthesis genes were remained,
      whereas others diverged in gene structure and/or expression pattern in maize. For
      most of the duplicated genes, one of the copies has disappeared in the maize
      genome after the WGD and the subsequent "diploidization".

PMID- 19593541
TI  - Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1
      diabetic patients.
AB  - AIMS/HYPOTHESIS: This study aimed to evaluate the prevalence of retinopathy in
      long-surviving type 1 diabetic patients. It also investigated the 25 year
      incidence of proliferative retinopathy and associated risk factors in a Danish
      population-based cohort. METHODS: A population-based cohort of 727 type 1
      diabetic patients from Fyn County, Denmark, was identified in 1973. In 1981-1982,
      baseline retinopathy was graded and other risk factors were assessed in 573
      patients. Twenty-five years later, 308 patients were still alive. Of these, 201
      (65.3%) were re-examined at follow-up in 2007-2008. RESULTS: The median age and
      duration of diabetes at follow-up were 58.8 and 43 years, respectively. At follow
      up, the prevalence of diabetic retinopathy was 97.0%. Non-proliferative
      retinopathy was found in 45.8%, and 51.2% had proliferative retinopathy. The 25
      year incidence of proliferative retinopathy was 42.9% among patients at risk. In
      a multivariate analysis, baseline HbA(1) (OR 2.14 per 1% increase, 95% CI 1.06
      4.31) and non-proliferative retinopathy (OR 4.61, 95% CI 1.94-11.0) were the only
      risk factors for incident proliferative retinopathy. The long-term incidence of
      proliferative retinopathy was not associated with baseline duration of diabetes,
      proteinuria, smoking, body mass index, maculopathy or systolic or diastolic blood
      pressure. CONCLUSIONS/INTERPRETATION: Retinopathy among long-surviving type 1
      diabetic patients is almost universal. Proliferative retinopathy was found in
      half of these patients. In addition, the 25 year incidence of proliferative
      retinopathy was high. Baseline glycaemic regulation and non-proliferative
      retinopathy were identified as risk factors for incident proliferative
      retinopathy.

PMID- 19593542
TI  - Skeletal myoblast transplantation for attenuation of hyperglycaemia,
      hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: We aimed to demonstrate the feasibility and efficacy of intra
      muscular transplantation of human skeletal myoblasts (hSkMs) for attenuation of
      hyperglycaemia and improvement of insulin sensitivity using a mouse model of type
      2 diabetes mellitus. METHODS: KK Cg-Ay/J mice, aged 12 to 14 weeks, underwent an
      initial intraperitoneal glucose tolerance test (GTT) and were divided into the
      following groups: KK control group, basal medium (M199) only; KK myoblast group,
      with hSkM transplantation; KK fibroblast group, with human fibroblast
      transplantation. Non-diabetic C57BL mice were used as an additional normal
      control and also had hSkM transplantation. Cells were transplanted intra
      muscularly into the skeletal muscles of the mice. All animals were treated with
      ciclosporin for 6 weeks only. HbA(1c) and fasting GTT, as well as serum
      adiponectin, cholesterol, insulin and triacylglycerol were studied. RESULTS:
      Immunohistochemistry studies showed extensive survival of the transplanted hSkMs
      in the skeletal muscles at 12 weeks, with nuclei of the hSkMs integrated into the
      host muscle fibres. Repeat GTT showed a significant decrease in glucose
      concentrations in the KK myoblast group compared with the KK control and KK
      fibroblast groups. The KK myoblast group also had reduced mean HbA(1c),
      cholesterol, insulin and triacylglycerol, and increased adiponectin compared with
      the KK control and KK fibroblast groups. C57BL mice showed no change in glucose
      homeostasis after hSkM transplant. CONCLUSIONS/INTERPRETATION: Human skeletal
      myoblast transplantation attenuated hyperglycaemia and hyperinsulinaemia and
      improved glucose tolerance in the KK mouse. This novel approach of improving
      muscle insulin resistance may be a potential alternative treatment for type 2
      diabetes mellitus.

PMID- 19593543
TI  - Bioremediation of nitrobenzene-polluted sediments by Pseudomonas putida.
AB  - Natural attenuation, biostimulation and bioaugmentation of nitrobenzene (NB)
      contaminated sediments were investigated and compared. The removal rate of NB
      from contaminated environments with bioaugmentation was much faster than with
      biostimulation and natural attenuation. Within 10 days, 6 mg/kg and 53 mg/L
      nitrobenzene in sediment and water, respectively, was degraded with the
      augmentation of Pseudomonas putida isolated from the contaminated sediment. There
      was no distinct performance difference between natural attenuation and
      biostimulation, demonstrating that addition of nutrients had no effect on the
      bioremediation process. The information on the current phase is a crucial step in
      making policy decisions for the application of bioremediation.

PMID- 19593544
TI  - Distribution of dissolved trace metals around the Sacrificos coral reef island,
      in the southwestern Gulf of Mexico.
AB  - A reef system in the southwestern Gulf of Mexico is affected by anthropogenic
      activities, sourced by urban, fluvial, and sewage waters. Dissolved metals have
      higher concentrations during the rainy season. V and Pb, were derived from an
      industrial source and transported to the study area by rain water. On the other
      hand, Jamapa River is the main source for Cu and Ni, which carries dissolved
      elements from adjacent volcanic rocks. Principal Component Analysis shows a
      common source for dissolved nitrogen, phosphates, TOC, and suspended matters
      probably derived from a sewage treatment plant, which is situated near to the
      study area.

PMID- 19593545
TI  - Unilateral pulmonary edema and shock: a diagnostic challenge.

PMID- 19593547
TI  - Anatomical double-bundle MPFL reconstruction with an aperture fixation.
AB  - Since biomechanical studies have shown that the medial patellofemoral ligament
      (MPFL) is the main restraint against lateral patella displacement, reconstruction
      of the MPFL has become an accepted method of restoring patellofemoral stability
      and numerous techniques were described. Due to biomechanical examinations and
      clinical results, an anatomical double-bundle reconstruction of the "sail-like"
      MPFL is a reasonable method for achieving stability during complete extension and
      lower flexion degree. This method also serves to avoid rotation of the patella,
      providing immediate stability throughout the normal range of motion. However,
      until today, an aperture fixation technique at the patellar insertion with two
      bundles has not been described previously. This technique can provide an
      immediate stability to allow an early rehabilitation with full range of motion.

PMID- 19593546
TI  - Tracking changes in cardiac output: methodological considerations for the
      validation of monitoring devices.
AB  - BACKGROUND: Until now, tools for continuous cardiac output (CO) monitoring have
      been validated as if they were tools for snapshot measurements. Most authors have
      compared variations in cardiac output between two time-points and used Bland
      Altman representations to describe the agreement between these variations. The
      impacts of time and of repetitive measurements over time are not taken into
      consideration. PURPOSE: This special article proposes a conceptual framework for
      the validation of CO monitoring devices. Four quality criteria are suggested and
      studied: (1) accuracy (small bias), (2) precision (small random error of
      measurements), (3) short response time and (4) accurate amplitude response.
      Because a tolerance is obviously admitted for each of these four criteria, we
      propose to add as a fifth criterion the ability to detect significant CO
      directional changes. Other important issues in designing studies to validate CO
      monitoring tools are reviewed: choice of patient population to be studied, choice
      of the reference method, data acquisition method, data acceptability checking,
      data segmentation and final evaluation of reliability. CONCLUSION: Application of
      this framework underlines the importance of precision and time response for
      clinical acceptability of monitoring tools.

PMID- 19593548
TI  - Arthroscopic suprascapular nerve decompression at the suprascapular notch.
AB  - Release of a transverse scapular ligament (TSL) is indicated for the entrapment
      of the suprascapular nerve (SSN). Previous arthroscopic techniques use step-wise
      reference landmarks leading to the notch to identify a TSL, and the key landmarks
      are the conoid ligament of the coracoclavicular ligament and the coracoid. This
      technique needs considerable amount of fibro-fatty tissue removal, which is time
      consuming procedure. The technique described herein uses the superior border of
      scapula as a key landmark. A lateral portal is used as a viewing portal, and an
      anterolateral portal, SSN portal, and accessory portal are required for the
      working portals. To identify the superior border of the scapula, dissection
      proceeds along the anterior border of the supraspinatus and advances medially
      into the supraspinatus fossa. Then, the TSL could be identified by palpating
      laterally along the superior border of scapula as a dimpling portion.

PMID- 19593549
TI  - A combined transglenoid and suture anchor technique for bony Bankart lesions.
AB  - We present a modified hybrid technique that is a combination of a transglenoid
      and suture anchor technique. Three-dimensional CT reconstruction is indicated for
      patients with bony fragments larger than 10 mm. First, a transglenoid technique
      is performed to reduce the bony fragment and then a suture anchor technique is
      performed to achieve a stable fixation. This combined technique is a useful
      arthroscopic procedure for the easy reduction and stable fixation of bony Bankart
      lesions.

PMID- 19593550
TI  - Insulin-like growth factor-1 protects preimplantation embryos from anti
      developmental actions of menadione.
AB  - Menadione is a naphthoquinone used as a vitamin K source in animal feed that can
      generate reactive oxygen species (ROS) and cause apoptosis. Here, we examined
      whether menadione reduces development of preimplantation bovine embryos in a ROS
      dependent process and tested the hypothesis that actions of menadione would be
      reduced by insulin-like growth factor-1 (IGF-1). Menadione caused a concentration
      dependent decrease in the proportion of embryos that became blastocysts. All
      concentrations tested (1, 2.5, and 5.0 microM) inhibited development. Treatment
      with 100 ng/ml IGF-1 reduced the magnitude of the anti-developmental effects of
      the two lowest menadione concentrations. Menadione also caused a concentration
      dependent increase in the percent of cells positive for the TUNEL reaction. The
      response was lower for IGF-1-treated embryos. The effects of menadione were
      mediated by ROS because (1) the anti-developmental effect of menadione was
      blocked by the antioxidants dithiothreitol and Trolox and (2) menadione caused an
      increase in ROS generation. Treatment with IGF-1 did not reduce ROS formation in
      menadione-treated embryos. In conclusion, concentrations of menadione as low as
      1.0 muM can compromise development of bovine preimplantation embryos to the
      blastocyst stage of development in a ROS-dependent mechanism. Anti-developmental
      actions of menadione can be blocked by IGF-1 through effects downstream of ROS
      generation.

PMID- 19593551
TI  - Supra-spinal circuits shape inhibitory postural adjustments anticipating
      voluntary index-finger flexion.
AB  - We previously observed that index finger flexion, with the prone hand, is
      preceded by an inhibitory postural adjustment (iAPA) in the Biceps Brachii (BB)
      electromyogram (EMG). The aim of this work is to locate the iAPA origin by
      testing the changes in spinal and cortico-spinal excitability during its
      development. Subjects were asked to flex their index finger, at will after an
      acoustic signal, while surface EMGs from Flexor Digitorum Superficialis (prime
      mover) and from BB (postural muscle) were recorded. In each experiment, tendon
      (T) reflexes in the resting BB and motor-evoked potentials elicited by magnetic
      cortical stimulation (CMEPs) in the resting, or in the slightly contracted BB,
      were collected both during the iAPA development and before the go signal. When BB
      was fully relaxed, T-reflexes falling in the iAPA temporal window were un
      modulated, while CMEPs were significantly inhibited; this inhibition occurred, on
      average, 37 ms before the iAPA onset indicating that iAPA sets up and develops at
      supraspinal level. Changes in CMEPs' excitability clearly anticipated the iAPA
      onset (about 50 ms) also when cortico-spinal excitability was probed in the
      active BB, thus indicating that this effect is likely due to a de-recruitment of
      spinal motoneurones. Thus, (1) iAPA is associated with voluntary movement even
      when postural muscles are at rest, (2) during iAPA spinal motoneurones are more
      likely disfacilitated than inhibited, and (3) the iAPA timing is regulated
      similarly to prime mover activation. All together these results suggest that
      iAPAs is fully sustained by inhibitory circuits located in the supra-spinal
      centres.

PMID- 19593552
TI  - Motor awareness in anosognosia for hemiplegia: experiments at last!
AB  - Anosognosia for hemiplegia (AHP) is the apparent inability to acknowledge
      contralesional paralysis, typically following right-hemisphere lesions. Here, we
      review studies that regard AHP as a specific deficit of motor awareness and
      explain its symptoms by employing an established computational model of motor
      control. These accounts propose that AHP arises from a breakdown in the
      monitoring of intended and actual movement. First, we critically examine
      physiological and behavioural experiments, which attempt to provide an account of
      AHP by verifying the presence or absence of motor intentions. We then review more
      recent experiments that endeavour to empirically address the hitherto unexplored
      role of motor intentions and internal representations of movements in AHP
      patients' non-veridical (illusory) awareness of movement. Finally, we consider
      implications of AHP research for clinical practice and the understanding of motor
      awareness more generally. We conclude that the false experience of movement in
      AHP may provide insight into what occurs when the mechanism responsible for
      monitoring and correcting significant discrepancies between predicted and
      executed actions is impaired. The system seems to continue to operate by
      deceiving awareness.

PMID- 19593553
TI  - Explicit eye movements failed to facilitate the precision of subsequent
      attentional localization.
AB  - This study investigated the usefulness of explicit spatial coordinates from eye
      movements for the precision of covert shifts of attention within dense arrays of
      items. Observers shifted their attention covertly from one item to the next in
      response to a series of beeps and reported the color of the disc on which the
      series ended, providing an estimate of the accuracy of the "attentional walk". We
      compared performance in this task when only covert shifts of attention were done
      to performance when observers first executed an explicit eye movement to the
      starting point of the attentional walk before beginning the covert attentional
      walk. The hypothesis was that the eye movement would activate explicit
      coordinates of the starting point of the attentional walk within brain systems
      that are involved in controlling both shifts of attention and eye movements. This
      in turn would provide an anchor for the attentional walk, thereby improving
      performance. The evidence did not support this hypothesis. Performance was no
      better with an explicit eye movement prior to the attentional walk than without
      one. This suggests that covert orienting--shifting attention--and overt orienting
      -shifting the eyes-access the same coordinate system and therefore activating new
      coordinates interferes with the old ones, no matter what the system of orienting
      is.

PMID- 19593554
TI  - The effect of high-frequency cutaneous vibration on different inputs subserving
      detection of joint movement.
AB  - Stimuli that preferentially activate rapidly adapting cutaneous receptors impair
      proprioception in the fingers. These experiments assessed potential mechanisms.
      The ability to detect passive movements about interphalangeal joints of the
      fingers was measured when vibrotactile stimuli were applied to the moving digit
      or to an adjacent digit at a high frequency (300 Hz) and low amplitude (50 microm
      peak-to-peak) that favours activation of Pacinian corpuscle (PC) afferents.
      Detection of movement was significantly impaired when vibration was applied to
      either digit. However, vibration applied to an anaesthetized adjacent digit
      caused no impairment. Impairment of proprioception was still observed when only
      skin and joint (but not muscle) afferents could contribute to detection, but was
      not significant with only muscle afferents intact during anaesthesia of the
      moving digit. We suggest that activation of PC afferents, either in or near the
      moving digit, impairs movement detection through an interaction predominantly
      between the classes of cutaneous afferents.

PMID- 19593555
TI  - Nitrogen transformations and diversity of ammonia-oxidizing bacteria in a desert
      ephemeral stream receiving untreated wastewater.
AB  - Levels of inorganic nitrogen species (ammonia, nitrite, and nitrate), ammonia
      oxidation potential (AOP), and diversity of ammonia-oxidizing bacteria (AOB) were
      studied in the sediments of a 50-km-long segment of an ephemeral stream in the
      Negev desert, receiving untreated wastewater. Water analysis in downstream
      sampling points showed reductions of 91.7% in biological oxygen demand, 87.7% in
      chemical oxygen demand, 73.9% in total nitrogen, and 72.8% in total ammonia
      nitrogen. Significant AOP levels in the sediment were detected mainly in the fall
      and spring seasons. Denaturing gradient gel electrophoresis of AOB 16S rRNA gene
      fragments showed that in most sampling points, the streambed was dominated by
      Nitrosospira cluster 3 strains similar to those dominating the stream bank's
      soils and sediments in nearby springs. Nitrosomonas strains introduced by
      discharged wastewater and others dominated some sections of the stream
      characterized by high organic carbon levels. The results suggest that climatic
      conditions in the Negev desert select for AOB belonging to Nitrosospira cluster
      3, and these conditions dominate the aquatic environment effect along most of the
      stream sections. In addition, the nitrification-denitrification processes were
      not sufficient to reduce nitrogen levels in the sediment and prevent the
      eutrophication of some sections of the stream ecosystem. Thus, the discharge of
      high nitrogen wastewater into desert streams should be done carefully as it may
      endanger the already fragile ecosystem.

PMID- 19593556
TI  - Genomic organization and biochemistry of the ribulose monophosphate pathway and
      its application in biotechnology.
AB  - 3-hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI) are
      key enzymes catalyzing exergonic reactions of the formaldehyde-fixing reaction
      and the isomerization of sugar phosphate in the ribulose monophosphate (RuMP)
      pathway. This pathway, which was originally found in methylotrophic bacteria, is
      now recognized to be widespread in prokaryotes and has been shown to be involved
      not only in formaldehyde fixation and detoxification but also in pentose
      phosphate biosynthesis. In this review, we describe the genomic organization and
      regulation of the genes of the RuMP pathway and then discuss the physiological
      roles of this pathway in prokaryotes. We further describe the biochemical
      properties of HPS and PHI. Heterologous expression of HPS and PHI in various
      organisms allows them to metabolize and detoxify formaldehyde, and we also review
      recent progress in such applications in biotechnology.

PMID- 19593557
TI  - Biocatalytic production of (S)-4-bromo-3-hydroxybutyrate and structurally related
      chemicals and their applications.
AB  - The enzymatic production of (S)-4-bromo-3-hydroxybutyrate has been poorly studied
      compared with (S)-4-chloro-3-hydroxybutyrate. This can be attributed to the
      toxicity of bromide for biocatalysis. Recently, we isolated cDNA that encodes
      Penicillium citrinum beta-keto ester reductase (KER) and the gene that encodes
      Leifsonia sp. alcohol dehydrogenase, which catalyzes the reduction of methyl 4
      bromo-3-oxobutyrate to methyl (S)-4-bromo-3-hydroxybutyrate with high optical
      purity and productivity and expressed them in Escherichia coli. Moreover, protein
      engineering was performed using error-prone PCR-based random mutagenesis to
      improve the thermostability and enantioselectivity of KER. This review focuses on
      the establishment of a novel biotechnological process for the production of (S)-4
      bromo-3-hydroxybutyrate using E. coli transformants. This process is suitable for
      industrial production of (S)-4-bromo-3-hydroxybutyrate, an intermediate for
      statin compounds.

PMID- 19593558
TI  - Baseline patterns of bone scintigraphy in patients with established post
      poliomyelitis paralysis.
AB  - INTRODUCTION: Post-poliomyelitis syndrome causes variable musculoskeletal
      manifestations including pain, muscle weakness and fatigue. These manifestations
      are commonly secondary to overuse and misuse of muscles and joints and could
      follow a fall. Bone scan can be useful in determining the underlying cause and
      follow-up. The objective of this study was to describe the late scintigraphic
      patterns on bone scan following poliomyelitis. MATERIALS AND METHODS: Bone scans
      of 8 adult patients (7 female and 1 male), aged 35 to 53 years, who were known to
      have paralytic poliomyelitis, were retrospectively studied. Six patients had
      unilateral while 1 had bilateral disease. All patients had three-phase bone scan
      and 5 had SPECT study as well. Studies were reviewed by two qualified nuclear
      medicine physicians and findings were recorded and analyzed. RESULTS: Several
      patterns were consistently identified: decreased blood pool activity in the
      affected lower limb of all patients; deformed ipsilateral hemi-pelvis with
      reduced uptake on the affected side in all patients with unilateral disease;
      stress changes with increased uptake in the bones of the contra-lateral lower
      extremity; and degenerative changes in multiple joints (shoulder, knee, hip,
      ankle and spine). Significant scoliosis was only noted in the patient with
      bilateral disease. CONCLUSION: Scintigraphic patterns on bone scan associated
      with the post-poliomyelitis syndrome and persistent weakness following a distant
      episode of poliomyelitis have been described. Awareness of these characteristic
      scintigraphic findings may facilitate an accurate diagnosis and lead to more
      appropriate patient management.

PMID- 19593559
TI  - Monitoring cancer therapy with PET: probably effective, but more research is
      needed.

PMID- 19593560
TI  - Cardiovascular events in Japanese asymptomatic patients with type 2  diabetes: a
      1-year interim report of a J-ACCESS 2 investigation  using myocardial perfusion
      imaging.
AB  - PURPOSE: Diabetic patients have a high risk for cardiovascular events. The role
      of myocardial perfusion imaging was investigated in asymptomatic diabetic
      patients to evaluate short-term prognosis in a Japanese population. METHODS: A
      total of 506 asymptomatic patients >= 50 years of age who had carotid artery
      maximum intima-media thickness >= 1.1 mm, urinary albumin excretion of >= 30 mg/g
      creatinine, with additional criteria of abdominal obesity, low HDL cholesterol,
      high triglyceride level, and hypertension were enrolled and followed up over a 3
      year period. Gated SPECT with stress-rest protocol was performed and analyzed by
      summed defect scores and QGS software. One-year cardiovascular events were
      analyzed. RESULTS: Myocardial ischemia was observed in 17% of patients, and
      abnormal perfusion findings of ischemia and/or scar were observed in 32% of
      patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events
      occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8
      had a higher incidence of either death or cardiovascular events. Event-free
      survival rates for SSS 0-3, 4-8, 9-13, and >= 14 were 0.96, 0.95, 0.82, and 0.76,
      respectively. Multivariate Cox regression analysis showed that significant
      variables were SSS, history of cerebrovascular accident, and electrocardiographic
      abnormality at rest. CONCLUSION: The 1-year interim summary showed that
      cardiovascular events were significantly higher in patients with SPECT
      abnormality, although hard cardiac event rate was relatively low. Targeted
      treatment strategy is required for asymptomatic but potentially high-risk
      diabetic patients.

PMID- 19593561
TI  - FDG PET/CT imaging in primary osseous and soft tissue sarcomas: a retrospective
      review of 212 cases.
AB  - PURPOSE: The aims of this study are to evaluate the sensitivity of FDG PET/CT for
      detection of soft tissue and osseous sarcomas on the basis of FDG avidity.
      METHODS: We retrospectively evaluated 212 consecutive patients with known soft
      tissue or osseous sarcoma who had undergone a FDG PET/CT study for the initial
      staging or assessment of recurrence of disease. The maximum standardized uptake
      value (SUVmax) of each primary and/or most intense metastatic lesion was measured
      and compared with the histological data provided in the final pathological
      reports. An SUVmax of 2.5 or greater was considered positive for our analysis.
      RESULTS: Sufficient histopathological data were available for 160 soft tissue
      sarcomas and 52 osseous sarcomas. FDG PET/CT detected 93.9% of all sarcomas with
      a sensitivity of 93.7% for soft tissue sarcomas and 94.6% for osseous sarcomas.
      The sensitivities of the most common sarcoma histologies were 100% for
      leiomyosarcomas, 94.7% for osteosarcomas, 100% for Ewing's sarcomas, 88.9% for
      liposarcomas, 80.0% for synovial sarcomas, 100% for gastrointestinal stromal
      tumors, 87.5% for malignant peripheral nerve sheath tumors, 100% for fibroblastic
      and myoblastic sarcomas, and 100% for malignant fibrohistiocytic tumors. The
      receiver-operating characteristic curve revealed an area under the curve of 94%
      for the discrimination of low-grade and high-grade sarcomas imaged for initial
      staging by FDG PET/CT. CONCLUSION: The combined metabolic and morphological
      information of FDG PET/CT imaging allows high sensitivity for the detection of
      various sarcomas and accurate discrimination between newly diagnosed low-grade
      and high-grade sarcomas.

PMID- 19593562
TI  - Assessment of long-term radiotoxicity after treatment with the low-dose-rate
      alpha-particle-emitting radioimmunoconjugate (227)Th-rituximab.
AB  - PURPOSE: The anti-CD20 antibody rituximab labelled with the alpha-particle
      emitting radionuclide (227)Th is of interest as a radiotherapeutic agent for
      treatment of lymphoma. Complete regression of human lymphoma Raji xenografts in
      60% of mice treated with 200 kBq/kg (227)Th-rituximab has been observed. To
      evaluate possible late side effects of (227)Th-rituximab, the long-term
      radiotoxicity of this potential radiopharmaceutical was investigated. METHODS:
      BALB/c mice were injected with saline, cold rituximab or 50, 200 or 1,000 kBq/kg
      (227)Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji
      xenografts treated with various doses of (227)Th-rituximab were also included in
      the study. Toxicity was evaluated by measurements of mouse body weight, white
      blood cell (WBC) and platelet counts, serum clinical chemistry parameters and
      histological examination of tissues. RESULTS: Only the 1,000 kBq/kg dosage
      resulted in decreased body weight of the BALB/c mice. There was a significant but
      temporary decrease in WBC and platelet count in mice treated with 400 and 1,000
      kBq/kg (227)Th-rituximab. Therefore, the no-observed-adverse-effect level (NOAEL)
      was 200 kBq/kg. The maximum tolerated activity was between 600 and 1,000 kBq/kg.
      No significant signs of toxicity were observed in histological sections in any
      examined tissue. There were significantly (p < 0.05), but transiently, higher
      concentrations of serum bile acids and aspartate aminotransferase in mice treated
      with either (227)Th-rituximab or non-labelled antibody when compared with control
      mice. The maximum tolerated dose to bone marrow was between 2.1 and 3.5 Gy.
      CONCLUSION: Therapeutically relevant dose levels of (227)Th-rituximab were well
      tolerated in mice. Bone marrow suppression, as indicated by decrease in WBC
      count, was the dose-limiting radiotoxicity. These toxicity data together with
      anti-tumour activity data in a CD20-positive xenograft mouse model indicate that
      therapeutic effects could be obtained with relatively safe dosage levels of the
      radioimmunoconjugate.

PMID- 19593563
TI  - Feasibility of integrated CT-liver perfusion in routine FDG-PET/CT.
AB  - OBJECTIVE: To integrate CT-perfusion into a routine, clinical contrast-enhanced
      (ce) PET/CT protocol for the evaluation of liver metastases and to compare
      functional CT and PET parameters. MATERIALS AND METHODS: Forty-six consecutive
      patients (mean age: 60 (34-82) years; 20 f, 26 m) with known liver lesions
      (colorectal metastases (n = 34), primary liver cancer (n = 4), breast cancer (n =
      3), anal cancer, gastric cancer, esophageal cancer, GIST, duodenal cancer (all: n
      = 1) who were referred for staging or therapy follow-up by [18F]-Fluoro-2-deoxy-D
      glucose-positron-emission-tomography/computed-tomography imaging (FDG-PET/CT)
      were included. After acquisition of a low-dose PET/CT, a split-injection (70-90
      mL) ce-CT-protocol, including a 35-s CT-perfusion scan of the liver and a
      diagnostic ce-CT of the thorax and/or abdomen (70 s delay, iv-contrast volume: 90
      mL, 4 mL/s) was performed. CT-perfusion parameters (BF, BV, MTT,) and semi
      quantitative PET-parameters (SUVmax, SUVmean, TLG, PETvol) were analyzed and
      compared. RESULTS: CT-perfusion data could be obtained in all but one patient
      with shallow breathing. In all patients, diagnostic ce-PET/CT quality was
      adequate without the use of additional contrast media. Significant correlations
      (P < 0.05) were found for each of BF, BV, MTT, and SUVmax, further, BF and MTT
      correlated with TLG. Several other correlations were seen for other perfusion and
      PET-parameters. CONCLUSION: Combined CT-perfusion/PET/CT-protocol without the use
      of additional contrast media is feasible and can be easily integrated in clinical
      routine. Perfusion parameters and PET-parameters are only partly correlating and
      therefore have to be investigated further at fixed time points during the course
      of disease and therapy.

PMID- 19593564
TI  - Calicum microdomains form within neutrophils at the neutrophil-tumor cell
      synapse: role in antibody-dependent target cell apoptosis.
AB  - Ca(2+) messages are broadly important in cellular signal transduction. In immune
      cells, Ca(2+) signaling is an essential step in many forms of activation.
      Neutrophil-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) is one
      form of leukocyte activation that plays an important role in tumor cell killing
      in vitro and in patient care. Using fluorescence methodologies, we found that
      neutrophils exhibit Ca(2+) signals during ADCC directed against breast
      fibrosarcoma cells. Importantly, these signals were localized to Ca(2+)
      microdomains at the neutrophil-to-tumor cell interface where they display dynamic
      features such as movement, fusion, and fission. These signals were blocked by the
      intracellular Ca(2+) buffer BAPTA. At the neutrophil-tumor cell synapse, the
      neutrophil's cytoplasm was enriched in STIM1, a crucial mediator of Ca(2+)
      signaling, whereas the Ca(2+)-binding proteins calbindin and parvalbumin were not
      affected. Our findings suggest that Ca(2+) microdomains are due to an active
      signaling process. As Ca(2+) signals within neutrophils were necessary for
      specific tumor cell apoptosis, a central role of microdomains in leukocyte
      mediated tumor cell destruction is indicated.

PMID- 19593565
TI  - A phase II study of biweekly pemetrexed and gemcitabine in patients with
      metastatic breast cancer.
AB  - PURPOSE: Pemetrexed (PEM) is a novel folate antimetabolite which inhibits
      thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide
      formyl transferase. This phase II study was designed to assess the efficacy of
      Gemcitabine (GEM) and PEM given in a novel schedule in metastatic breast cancer
      (MBC) patients. METHODS: Eligible patients had MBC and received one prior
      chemotherapy regimen for metastatic disease; Performance status (PS) 0-2;
      measurable disease (RECIST criteria). PEM(500 mg/m2) was administered
      intravenously (IV) over 10 min prior to GEM(1,500 mg/m2) IV given over 30 min on
      day 1 every 14 days. RESULTS: Median age of the 16 patients in the study was 54
      years (range 33-77). Fourteen patients had a PS of 0/1 and were evaluable for
      response. There were no reported complete or partial responses, seven patients
      with stable disease, six patients with disease progression and one patient with
      unknown response. Most common toxicities were skin rash: Grade 1/2(8) and Grade
      3/4(1). Grade 3/4 non-hematological toxicities were fatigue(1); anorexia(1);
      pneumonia(1); peripheral ischemia(1) and elevation of liver transaminases(1).
      Three patients experienced febrile neutropenia (FN). This study did not meet the
      predefined criteria to proceed with additional accrual. CONCLUSIONS: This regimen
      of PEM and GEM showed no clinical activity in the dose and schedule tested.

PMID- 19593566
TI  - Pharmacokinetics and tissue distribution of PGG-paclitaxel, a novel
      macromolecular formulation of paclitaxel, in nu/nu mice bearing NCI-460 lung
      cancer xenografts.
AB  - PURPOSE: PGG-PTX is a water-soluble formulation of paclitaxel (PTX), made by
      conjugating PTX to poly(L-gamma-glutamylglutamine) acid (PGG) via ester bonds,
      that spontaneously forms a nanoparticle in aqueous environments. The purpose of
      this study was to compare the pharmacokinetics and tissue distribution of PTX
      following injection of either free PTX or PGG-PTX in mice. EXPERIMENTAL DESIGN:
      Both [3H]PTX and PGG-[3H]PTX were administered as an IV bolus injection to mice
      bearing SC NCI-H460 lung cancer xenografts at a dose of 40-mg PTX equivalents/kg.
      Plasma, tumor, major organs, urine, and feces were collected at intervals out to
      340 h. Total taxanes, taxane extractable into ethyl acetate, and native PTX were
      quantified by liquid scintillation counting and HPLC. RESULTS: Conjugation of PTX
      to the PGG polymer increased plasma and tumor Cmax, prolonged plasma half-life
      and the period of accumulation in tumor, and reduced washout from tumor. In
      plasma injection of PGG-PTX increased total taxane AUC0-340 by 23-fold above that
      attained with PTX. In tumors, it increased the total taxane by a factor of 7.7,
      extractable taxane by 5.7, and native PTX by a factor of 3.5-fold. Conjugation
      delayed and reduced total urinary and fecal excretion of total taxanes.
      CONCLUSIONS: Incorporation of PTX into the PGG-PTX polymer significantly
      prolonged the half-life of total taxanes, extractable taxane, and native PTX in
      both the plasma and tumor compartments. This resulted in a large increase in the
      amount of active PTX delivered to the tumor. PGG-PTX is an attractive candidate
      for further development.

PMID- 19593567
TI  - Severity of Carpal tunnel syndrome assessed with high frequency ultrasonography.
AB  - Although nerve conduction study (NCS) is the method most frequently used in daily
      clinical practice to confirm clinical diagnosis of Carpal tunnel syndrome (CTS),
      ultrasonographic (US) measurement of the median nerve cross-sectional area is
      both sensitive and specific for the diagnosis of CTS. Moreover, an algorithm
      evaluating CTS severity based on CSA of median nerve was suggested. This study is
      aimed to investigate the clinical usefulness of this algorithm in assessing CTS
      severity. The patients underwent a full clinical examination, including Tinel and
      Phalen test, and questioned about symptoms and the secondary causes of CTS. All
      of the patients refilled a Turkish version Levine Boston Carpal tunnel syndrome
      questionnaire (BQ) and the visual analog scale for pain (VAS 0-100 mm) A MyLab 70
      US system (Esaote Biomedica, Genoa, Italy) equipped with a broadband 6-18 MHz
      linear transducer was used for US examination. The cross-sectional area of the
      median nerve was measured at the proximal inlet of the carpal tunnel (US cut-off
      points that discriminate between different grades of CTS severity as 10.0-13.0
      mm(2) for mild symptoms, 13.0-15.0 mm(2) moderate symptoms and >15.0 mm(2) for
      severe patients). Nerve conduction studies were carried out, and severity of
      electrophysiological CTS impairment was reported as normal, mild, moderate,
      severe and extreme. The agreement between NCS and US in showing CTS severity
      (normal, mild, moderate and severe) was calculated with Cohen's kappa
      coefficient. Ninety-nine wrists of 54 patients (male/female: 4/50) were included
      in the study. Mean ages of patients were (+/-SD) 43.3 +/- 11 years. Forty-nine
      patients had idiopathic CTS, whereas five had secondary CTS (4 had diabetes
      mellitus and 1 had hypothyroidism). Symptoms were bilateral in 45 patients
      (83.3%). There were statistical differences between the groups according to
      electrophysiologic severity scale in terms of age (P < 0.001), body-mass index (P
      = 0.034), VAS (P = 0.014), Boston symptom severity (P = 0.013) and CSA of median
      nerve (P < 0.001). The identification of CTS severity showed substantial
      agreement (Cohen's kappa coefficient = 0.619) between the US and NCS. Also the
      four groups based on US CTS severity classification were significantly different
      in VAS (P = 0.017) and Boston symptom severity (P = 0.021). The median nerve
      swelling detected by calculation of the CSA reflects in itself the degree of
      nerve damage as expressed by the clinical picture. In addition to CTS diagnosis,
      sonographic measurement of CSA could also give additional information about
      severity of median nerve involvement. Using of US may cost-effectively reduce the
      number of NCS in patients with suspected CTS.

PMID- 19593568
TI  - Efficacy of SLZ and MTX (alone or combination) on the treatment of active
      sacroiliitis in early AS.
AB  - Sacroiliitis is an important sign of spondylarthritis (SpA) of which the
      prototype disease is ankylosing spondylitis. The radiographic changes required
      for diagnosing AS occur as late as 8-11 years after the onset of clinical
      symptoms. Nonsteroid anti-inflammatory drugs (NSAIDs) have been the main
      treatment for spondylitis of AS. For patients refractory or intolerant to NSAIDs,
      disease-modifying antirheumatic drugs (DMARDs) have been used as a second-line
      approach. Sulphasalazine (SLZ) is known as the best DMARD in treatment of
      peripheral arthritis; also methotrexate (MTX) is currently one of the most widely
      used DMARDs. But there was no objective information about inflammation of
      sacroiliac joints during treatment with these DMARDS that are the first places of
      the beginning point of SpA. For this purpose, in this study, the effect of SLZ
      and MTX, which are used alone and combination in 6 months, on treatment of active
      sacroiliitis, which is shown by dynamic magnetic resonance and acute phase
      reactants in laboratory has been investigated. 55 patients (F:M = 34:21) with
      active sacroiliitis [mean age = 37.05 + 13.03 year (n = 55)] were evaluated and
      determined by dynamic magnetic resonance imaging in this study. The better
      response in the SLZ treatment group than the other two groups has been obtained.
      Nevertheless, those changes were not statistically found different. In
      conclusion, the ratio of treatment of active sacroiliitis, especially early
      period, with SLZ as a DMARD is better than MTX or MTX + SLZ, but this difference
      is not statistically significant. A prospective study of the treatment of active
      sacroiliitis by DMARDs may be more illustrative.

PMID- 19593569
TI  - Perceived functional disabilities among rheumatoid arthritis patients.
AB  - The aim of this study was to determine from patient perspective the most relevant
      physical functions when estimating the functional disabilities, and to estimate
      the perceived relative influence of them. Structured telephone interviews were
      conducted among 143 RA patients. The subjects were asked to name functions and
      activities in their everyday life, which were affected by RA. After this, they
      were asked to score each of the named item with a scale from 0 to 100. These were
      combined with earlier collected data on sociodemographic background and clinical
      status. Listed activities were grouped to functional disabilities and further
      categorized according to joints, limbs and body areas. One or more functional
      disabilities affecting everyday life because of RA was mentioned by 87.4%,
      altogether 354 mentions. The most commonly mentioned disabilities were walking
      and opening jars. However, the most commonly mentioned disabilities were not
      those with highest perceived disabilities. Of the 59 different types of
      disabilities mentioned, 25 were connected with movements of the shoulder, 30 with
      elbow, 40 with wrist, and 37 with fingers. Movements of the back were involved in
      20 mentioned disabilities, hip and knee both in 8, and ankles in 6. Disabilities
      related to lower extremity functions were considered most disabling. In
      conclusion, to describe RA patients' functional disability, the measured
      functions should be those which the patients themselves consider relevant and
      causing disability. Furthermore, the studied functional measures ought to be
      weighted according to the relative influence of each function to the patients.

PMID- 19593570
TI  - Macrophage activation syndrome in malaria.
AB  - Macrophage activation syndrome (MAS) is a clinical syndrome caused by an
      excessive proliferation of T lymphocytes and well-differentiated macrophages; an
      entity distinct from malignant histiocytosis. Although rheumatologic conditions
      are the common cause of MAS, a wide range of infections are also seen to cause
      MAS. We report an adolescent with severe Plasmodium falciparum malaria and MAS.
      He fulfilled six out of eight criteria required to diagnose hemophagocytic
      lymphohistiocytosis.

PMID- 19593571
TI  - Field performance evaluation and genetic integrity assessment of cryopreserved
      papaya clones.
AB  - This paper is the first report of field performance and evaluation of
      morphological traits following cryopreservation in four genotypes of Carica
      papaya (Z6, 97, TS2 and 35). It also describes the successful establishment of in
      vitro plantlets following vitrification-based cryopreservation of shoot tips and
      their acclimatisation through to field establishment. Cloned plants resulting
      from untreated controls, as well as controls taken at three other stages of the
      cryopreservation process (dissection, pre-treatment, plant vitrification solution
      2 (PVS2) treatment) and cryopreserved plants were established to ensure a
      rigorous appraisal of any variation. Results indicate no differences between any
      of the control plants or cryopreserved plants for either growth performance or
      morphology. In addition, both randomly amplified DNA fingerprinting and amplified
      DNA methylation polymorphism markers were used to assess any genomic or
      methylation changes in genotype 97 at four different developmental stages post
      cryopreservation (in vitro, acclimatisation and field). Only small genomic DNA
      modifications (0-8.3%) were detected in field stage plants and methylation
      modifications (0-4.3%) were detected at both the in vitro and field stages for
      samples treated with PVS2 or cryopreservation.

PMID- 19593572
TI  - [Intermittent elevation deficiency].
AB  - A 7-year-old boy presented with vertical double images. A paediatric examination
      and magnetic resonance imaging of the head did not show any pathological
      findings. The diagnosis was an acquired click syndrome of the superior oblique
      muscle. In cases with inflammatory and systemic origin the underlying disease
      should be treated. Local steroid therapy can be carried out for improvement of
      inflammation in the region of the superior oblique muscle with a high degree of
      suffering.

PMID- 19593573
TI  - Increased spontaneous apoptosis, but not survivin expression, is associated with
      histomorphologic response to neoadjuvant chemoradiation in rectal cancer.
AB  - PURPOSE: Survivin has been shown to be an important mediator of cellular
      radioresistance in vitro. This study aims to compare survivin expression and
      apoptosis to histomorphologic responses to neoadjuvant radiochemotherapy (RCT) in
      rectal cancer. MATERIALS AND METHODS: Thirty-six pre-treatment biopsies were
      studied. Survivin mRNA and protein expression plus TUNEL staining for apoptosis
      was performed. Response to treatment was assessed using a 5-point tumour
      regression grade. RESULTS: Survivin expression was not found to be predictive of
      response to RCT (p = NS). In contrast, spontaneous apoptosis was significantly (p
      = 0.0051) associated with subsequent response to RCT. However, no association
      between survivin expression and levels of apoptosis could be identified.
      CONCLUSIONS: This in vivo study failed to support in vitro studies showing an
      association between survivin and response to chemotherapy and radiation therapy.
      These results caution against the translation of the in vitro properties of
      survivin into a clinical setting.

PMID- 19593574
TI  - [Pulmonary arterial hypertension in collagenoses].
AB  - Pulmonary arterial hypertension is a rare disease of small pulmonary arteries of
      unknown origin characterised by endothelial dysfunction and cellular
      proliferation throughout all vessel layers, resulting in progressively elevated
      pulmonary arterial resistance with increasing right heart strain and finally
      right heart failure. The condition may develop in connective tissue diseases with
      variable frequency leading to a substantial worsening of prognosis. However, the
      spectrum of therapeutic options has broadened significantly in recent years.
      Several compounds have gained approval that act mainly as pulmonary vasodilators.
      Further drugs are under investigation, some of which target pulmonary vascular
      remodeling. Echocardiography remains the primary examination for disease
      detection. To classify pulmonary hypertension definite hemodynamic evaluation by
      means of right heart catheterisation and a thorough differential diagnosis are
      essential to provide the basis for further treatment. For differential therapy
      and assessment of follow-up profound knowledge is required, pointing to the need
      for close cooperation with specialised centres.

PMID- 19593575
TI  - [MMP- and FAP-mediated non-inflammation-related destruction of cartilage and bone
      in rheumatoid arthritis].
AB  - INTRODUCTION: Due to morphological similarities of high-grade synovitis in
      rheumatoid Arthritis (RA) and mesenchymal, semimalignant tumors and the
      hypothesis that RA progression is not only inflammation-related, but also
      determined by tumor-like mechanisms, a comparison was made between expression
      profiles of RA, giant cell tumor of bone (GCT) and normal synovium (ND). METHODS:
      Array data of selected genes were validated through immunohistochemical staining
      of paraffin-embedded and deep frozen tissue samples of GCT, RA and normal
      synovium. RESULTS: With microarray analysis, CCR1, CCR5, MMP-1, MMP-2, MMP-3, MMP
      9, MMP-14 and FAP were found to be significantly upregulated in RA and GCT
      compared to ND. A significant upregulation in RA and GCT compared to ND could be
      validated by immunohistochemistry for MMP-1, MMP-9, MMP-14 and FAP. DISCUSSION:
      For MMPs, and MMP-9 in particular, an important role in early cartilage
      destruction of RA was suggested. The presence of FAP in RA and in stroma of a
      semimalignant tumor indicates tumor-like tissue destruction in chronic synovitis
      associated with RA.

PMID- 19593576
TI  - Accuracy of minimally invasive navigated acetabular and iliosacral fracture
      stabilization using a targeting and noninvasive registration device.
AB  - BACKGROUND: To assess the feasibility and accuracy of guide pin (GP) placement
      using a combined noninvasive patient immobilization and stereotactic targeting
      system in computer-assisted percutaneous pelvic fracture stabilization. METHODS:
      A total of 12 patients with negligible dislocated unstable pelvic fractures were
      enrolled in this study, performed between February 2002 and October 2005. Our
      original plans included 13 GP placements in the iliosacral area (SF) and 8 in the
      acetabular (AF) area. Patients were bedded on a noninvasive dual-vacuum
      immobilization device. Interventions were planned on a navigation system using
      intraoperatively acquired CT data. Radiodense markers glued to the skin and the
      immobilization device provided synchronization between virtual data set and real
      anatomical situation. A stereotactic targeting device was used for stabilization
      of GP tracking. GP positions were verified intraoperatively by CT, followed by
      fracture stabilization with cannulated screws. RESULTS: Mean GP placement
      accuracy according to plan: (1) SF-cohort: 2.8 mm (SD 2.0 mm, range 0.5-9.0 mm)
      at the bony entry point and 3.8 mm (SD 2.3 mm, range 0.6-9.5 mm) at the target
      point. (2) AF-cohort: 3.0 mm (SD 0.9 mm, range 1.6-4.9 mm) at the bony entry
      point and 3.9 mm (SD 1.9 mm, range 1.6-7.5 mm) at the target point. GP placement
      succeeded optimally in 11 out of 13 cases in the SF-cohort, and 6 out of 8 cases
      in the AF-cohort. The individual average dose-length product (DLP) per successful
      finished procedure was 1,576 mGy x cm (SD 812 mGy x cm, range 561-2,739 mGy x
      cm). CONCLUSION: Our findings substantiate application of the noninvasive patient
      immobilization and stereotactic targeting system as effective in computer-assited
      percutaneous stabilization of sacral bone fractures/SI joint disruptions and
      coronally oriented acetabular dome fractures. We recommend according to the ALARA
      (as low as reasonable achievable) principle: first, the kV and mAs values have to
      be reduced. Second, the scanned volume has to be strictly limited to the area of
      interest. Third, the number of control CTs have to be minimized. Also, the IsoC
      might be a better choice for implant tracking below 12 cm to reduce the radiation
      dose to the minimum. We believe that for all high-precise GP placements in the
      acetabular column area, further improvements in GP guidance (inhibiting pin tip
      slipping and detecting intraosseous GP deflection) are necessary.

PMID- 19593577
TI  - Severe early onset hemolysis, elevated liver enzyme, and low platelet-syndrome in
      2 subsequent pregnancies: case report and review of the literature.
AB  - BACKGROUND: Pregnancies after a previous pregnancy complicated by hemolysis,
      elevated liver enzyme, and low platelet (HELLP) syndrome carry an increased risk
      of HELLP-syndrome. CASE REPORT: We report on a 35-year-old patient with both
      HELLP-syndrome and fatal neonatal outcome in two subsequent pregnancies with
      delivery by cesarean section in the 26th and 27th gestational weeks,
      respectively. The children were immediately admitted to the neonatal intensive
      care unit but died in their postpartum period. Before the second pregnancy
      testing for antiphospholipid-syndrome revealed normal results. CONCLUSION: In
      general, pregnancies after HELLP-syndrome carry increased risks for pregnancy
      related complications. Evaluation of the immunologic status and application of
      immune-globulins could be diagnostic and therapeutic options in our case. Further
      research is recommended to evaluate the mechanisms of recurrence of HELLP
      syndrome.

PMID- 19593578
TI  - Effects of hormone replacement therapy on glucose and lipid profiles and on
      cardiovascular risk parameters in postmenopausal women.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of hormone
      replacement therapy (HRT) on carbohydrate and lipid metabolisms and
      cardiovascular risk parameters in healthy postmenopausal women. METHODS: Forty
      women receiving and 38 women not receiving HRT were included and baseline and
      sixth month blood pressure, weight, body mass index, waist/hip ratio, blood lipid
      profile, inflammatory markers (homocysteine, C-reactive protein (CRP) and
      fibrinogen), hemoglobin A1c (HbA1c) and insulin, and oral glucose tolerance test
      (OGTT) results were evaluated. RESULTS: The mean age was 52.6+/-4.9 and 52.2+/
      5.0 years in the HRT and Control Groups, respectively. Whereas there was no
      change in the Controls, the weight, waist/hip ratio, and BMI increased and
      diastolic blood pressure decreased in the HRT patients. LDL-c, VLDL-c and
      lipoprotein (a) levels were significantly higher in the HRT Group in the sixth
      month; however, total cholesterol and LDL-c increased in the Controls but VLDL-c
      and lipoprotein (a) did not. CRP and homocysteine significantly increased and
      fibrinogen decreased, whereas in the Control Group no significant change was
      detected. A significant improvement in HbA1c and OGTT was found in both the
      groups, whereas a significant reduction was measured only in the HRT Group.
      CONCLUSIONS: In response to 6 months of HRT, there was an increase in weight,
      BMI, and waist/hip ratio as known cardiovascular risk factors, but no significant
      impact on lipid profile and glucose metabolism could have been clearly
      demonstrated. A mixed effect profile of HRT on the state of inflammation
      (increase in CRP and homocysteine, decrease in fibrinogen) was observed.

PMID- 19593579
TI  - The clinical utility of oral glucose tolerance test at term: can it predict fetal
      macrosomia?
AB  - OBJECTIVE: The goal of this study was to assess the correlation between true
      fetal macrosomia and abnormal oral glucose tolerance test (OGTT) in pregnant
      women at term gestation who had a negative glucose challenge screen (GCT) at 24
      28 weeks. STUDY DESIGN: In this cohort observational study, we enrolled all term
      pregnant patients who presented to our antenatal unit with estimated fetal weight
      >90th percentile (or >4,000 g) and negative 50 g GCT. The women underwent a 3-h
      (100 g) OGTT test. Patient's demographics, GCT and OGTT test results, mode of
      delivery and pregnancy outcomes were recorded and analyzed. RESULTS: One hundred
      and seventy women (mean age 30.2+4.6 years, range 19-44) were recruited over 15
      month period. Ten patients (5.9%) were identified as having impaired glucose
      metabolism at term. In this sub-group, we found no correlation between GCT values
      at 24-28 weeks, family history of diabetes mellitus, the patient's BMI or weight
      at term, and the diagnosis of impaired glucose metabolism. There was no
      statistically significant difference in the mean fetal weight in patients with
      normal and abnormal OGTT. No shoulder dystocia or third and fourth degree vaginal
      tears were reported among the women with suspected fetal macrosomia and impaired
      glucose metabolism. CONCLUSIONS: There was no correlation between true fetal
      macrosomia and an abnormal 3-h (100 g) OGTT at term. A larger-scale study is
      needed to determine the clinical significance of performing an OGTT at term for
      all patients with macrosomia and negative gestational diabetes screen.

PMID- 19593580
TI  - Driving simulator performance and psychomotor functions of schizophrenic patients
      treated with antipsychotics.
AB  - The objective of the study is to compare schizophrenic inpatients under
      antipsychotic monotherapy regarding simulated driving behaviour and psychomotor
      functions related to driving ability. Schizophrenic inpatients (n = 80) were
      tested before discharge to outpatient treatment. Data were collected with the
      computerized Act & React Testsystem and the Wiener Testsystem measuring visual
      perception, reaction time, attention, vigilance and stress-tolerance. Besides,
      patients underwent various driving simulations on a static driving simulator (FT
      SR 200). Before discharge to outpatient treatment, about 25% of schizophrenic
      patients must be considered as severely impaired with respect to driving skills.
      Differences between treatment groups could be shown both in psychomotor measures
      and in driving simulator performance with a better test performance of patients
      treated with atypical antipsychotics. Controlling for age, psychopathologic
      symptoms and extrapyramidal signs, differences in psychomotor measures were most
      pronounced in concentration and vigilance. As mental disorders itself pose an
      increased risk of accidents, counselling patients with respect to differential
      effects of antipsychotic treatment is of great relevance. In addition to
      psychomotor tests computer-simulated driving seems to be a useful tool in
      assessing traffic safety under pharmacologic treatment.

PMID- 19593581
TI  - Quality of life (EQ-5D) and hand-arm vibration syndrome.
AB  - BACKGROUND: The aim of this study was to investigate the quality of life of a
      population of Finnish metalworkers who were exposed to hand-arm vibration (HAV)
      and who suffered from white fingers, tingling, or numbness of the fingers,
      musculoskeletal disorders of the upper extremities, or symptoms of carpal tunnel
      syndrome (CTS). METHODS: A questionnaire on vibration exposure in the workplace
      and symptoms relating to the upper extremities was sent to a sample (n = 530) of
      members of the local Metalworkers Union. Of those who reported vibration-induced
      white fingers (VWF), numbness or tingling of the fingers, or symptoms of CTS, 131
      men participated in clinical examinations. Their cumulative lifelong exposure to
      HAV was evaluated, and the health-related quality of life was assessed using
      EuroQoL(EQ)-5D. RESULTS: There was an inverse relationship between the EQ-5D
      index score and cumulative exposure to HAV: as exposure to HAV increased, the
      quality of life became more impaired (P < 0.001). Vascular, sensorineural, and
      musculoskeletal symptoms and symptoms of CTS decreased significantly with the EQ
      5D index score, sensorineural symptoms causing the most significant impairment in
      EQ-5D dimensions of mobility, usual activities, pain/discomfort, and
      anxiety/depression). The mean EQ-5D index and the visual analogic scale (VAS)
      score were lower for those patients who complained of difficulties at work or
      during leisure time due to HAVS symptoms. CONCLUSION: The findings of the present
      study suggest that symptoms related to HAV exposure significantly diminish the
      quality of life. This impairment can be seen in the different dimensions of well
      being that are measured by EQ-5D. EQ-5D seems to correlate with both the severity
      of symptoms and the cumulative exposure index, and can thus be recommended as
      part of the health examination of workers exposed to HAV.

PMID- 19593582
TI  - PKC epsilon facilitates recovery of exocytosis after an exhausting stimulation.
AB  - It has been well documented that protein kinase Cs (PKCs) play multifaceted roles
      in regulating exocytosis of neurotransmitters and hormones. But the isoform
      specific PKC effects are still poorly elucidated mainly because of the large
      variety of PKC isoforms and the dubious specificity of the commonly used
      pharmacological agents. In the present study, based on overexpression of wild
      type or dominant negative PKC epsilon, we demonstrate in neuroendocrine PC12
      cells that PKC epsilon, but not PKC alpha, facilitates recovery of exocytosis
      after an exhausting stimulation. Specifically, PKC epsilon mediates fast recovery
      of the extent of exocytosis in a phosphatidylinositol biphosphate-dependent
      manner, likely through enhancing the rate of vesicle delivery and reorganization
      of cortical actin network. In addition, PKC epsilon promotes fast recovery of
      vesicle release kinetics that is slowed after a strong stimulation. These
      experimental results may suggest a PKC-dependent mechanism relevant to the short
      term plasticity of exocytosis in both neurons and neuroendocrine cells.

PMID- 19593583
TI  - The prognostic significance of preoperative plasma levels of osteopontin in
      patients with TNM stage-I of hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the prognostic value of preoperative plasma osteopontin
      (OPN) levels in patients with early stage of hepatocellular carcinoma (HCC).
      METHODS: Preoperative plasma levels of OPN were detected by ELISA in 68 patients
      with tumor-node metastasis system stage-I of HBV-related HCC, and their
      association with tumor recurrence or patients' survival was analyzed. RESULTS:
      The median plasma OPN level of patients was 82.51 ng/ml (25-75% interquartile
      range, 63.15-110.45 ng/ml). Plasma OPN levels in patients with tumor size C5 cm
      in diameter were significantly higher than that of patients with tumor size?5 cm
      in diameter (104.76 vs.75.16 ng/ml, P = 0.003). When the 100 ng/ml was used asa
      cut-off value to divide the patients into two groups: the higher plasma OPN group
      and the lower plasma OPN group, the tumor recurrence rate of the higher plasma
      OPN group was significantly higher than that of the lower plasma OPN group (52.17
      vs. 24.44%, P = 0.022). Meanwhile, the recurrence rate of the patients with
      positive alpha fetoprotein (AFP) (45.5%) was significantly higher than that of
      those negative AFP patients (12.5%,P = 0.006). A higher plasma OPN level was one
      leading independent prognostic factor for both overall survival(OS) and relapse
      free survival in multivariate Cox models. CONCLUSION: The preoperative plasma OPN
      level and serum AFP level in patients with early stage of HCC can be used as a
      prognostic marker for early stage of HCC.

PMID- 19593584
TI  - Evaluation of anti-leishmanial activity of selected Indian plants known to have
      antimicrobial properties.
AB  - The severe toxicity, exorbitant cost and the emerging resistance of Leishmania
      spp. against most of the currently used drugs led to the urgent need for
      exploiting our traditional Ayurvedic knowledge to treat visceral leishmaniasis.
      The aim of this study was to evaluate the in vitro anti-leishmanial activity of
      various extracts from ten traditionally used Indian medicinal plants. The
      methanolic extract from only two plants, Withania somnifera Dunal (ashwagandha)
      and Allium sativum Linn. (garlic), showed appreciable activity against Leishmania
      donovani. Further active compounds from these two plants were isolated and
      purified based on bioactivity-guided fractionation. HPLC-purified fraction A6 of
      ashwagandha and G3 of garlic showed consistently high activity with 50%
      inhibitory concentration (IC(50)) of 12.5 +/- 4 and 18.6 +/- 3 microg/ml against
      promastigotes whereas IC(50) of 9.5 +/- 3 and 13.5 +/- 2 microg/ml against
      amastigote form, respectively. The fraction A6 of ashwagandha was identified as
      withaferin A while fraction G3 of garlic is yet to be identified, and the work is
      in progress. Cytotoxic effects of the promising fractions and compounds were
      further evaluated in the murine macrophage (J774G8) model and were found to be
      safe. These compounds showed negligible cytotoxicity against J774G8 macrophages.
      The results indicate that fraction A6 of ashwagandha and fraction G3 of garlic
      might be potential sources of new anti-leishmanial compounds. The in vivo
      efficacy study and further optimization of these active compounds are in
      progress.

PMID- 19593585
TI  - Morphological and genetical description of Loma psittaca sp. n. isolated from the
      Amazonian fish species Colomesus psittacus.
AB  - A previously unrecognised fish-infecting microsporidia (Loma psittaca n. sp.),
      found adherent to the intestinal mucosa of the freshwater puffer fish Colomesus
      psittacus (Teleostei, Tetraodontidae) from lower Amazon River, was described
      based on light and transmission electron microscope and phylogenetic analysis.
      The whitish xenoma was completely filled by numerous spores, including several
      developmental stages of the parasite. In all of these stages, the nuclei were
      monokaryotic. The merogonial plasmodium divided by binary fission and the sporont
      gave rise to disporoblastic ovoid spores measuring 4.2 +/- 0.4 x 2.8 +/- 0.4
      microm. In mature spores, the polar filament was arranged in 10-11 (rarely 12)
      coils in one row in turn of posterior vacuole. The polaroplast had two distinct
      regions around the manubrium. The polyribosomes were organised in coiled tapes.
      The small subunit rRNA gene was sequenced and maximum parsimony analysis placed
      the microsporidian described here in the clade that includes the genera
      Ichthyosporidium, Loma and Pseudoloma. Based on differences from previously
      described microsporidians, such as ultrastructural characteristics of the xenoma,
      developmental stages including the spore and phylogenetic analysis supported the
      recognition of a new species, herein named L. psittaca n. sp.

PMID- 19593587
TI  - Competition and drought limit the response of water-use efficiency to rising
      atmospheric carbon dioxide in the Mediterranean fir Abies pinsapo.
AB  - The gas-exchange and radial growth responses of conifer forests to climatic
      warming and increasing atmospheric CO2 have been widely studied. However, the
      modulating effects of variables related to stand structure (e.g., tree-to-tree
      competition) on those responses are poorly explored. The basal-area increment
      (BAI) and C isotope discrimination (C stable isotope ratio; delta13C) in the
      Mediterranean fir Abies pinsapo were investigated to elucidate the influences of
      stand competition, atmospheric CO2 concentrations and climate on intrinsic water
      use efficiency (WUEi). We assessed the variation in delta13C of tree-rings from
      dominant or co-dominant trees subjected to different degrees of competition. A
      high- (H) and a low-elevation (L) population with contrasting climatic
      constraints were studied in southern Spain. Both populations showed an increase
      in long-term WUEi. However, this increase occurred more slowly at the L site,
      where a decline of BAI was also observed. Local warming and severe droughts have
      occurred in the study area over the past 30 years, which have reduced water
      availability more at lower elevations. Contrastingly, trees from the H site were
      able to maintain high BAI values at a lower cost in terms of water consumption.
      In each population, trees subjected to a higher degree of competition by
      neighboring trees showed lower BAI and WUEi than those subjected to less
      competition, although the slopes of the temporal trends in WUEi were independent
      of the competitive micro-environment experienced by the trees. The results are
      consistent with an increasing drought-induced limitation of BAI and a decreasing
      rate of WUEi improvement in low-elevation A. pinsapo forests. This relict species
      might not be able to mitigate the negative effects of a decrease in water
      availability through a reduction in stomatal conductance, thus leading to a
      growth decline in the more xeric sites. An intense and poorly asymmetric
      competitive environment at the stand level may also act as an important
      constraint on the adaptive capacity of these drought-sensitive forests to
      climatic warming.

PMID- 19593586
TI  - Seventy-five years of Resochin in the fight against malaria.
AB  - The four different forms of human malaria have threatened humanity since time
      immemorial and to this day, they exact a death toll of one to three million
      people annually. Synthetic anti-malarial agents have been in development since
      early 1900. Perhaps the most successful and widely used drug, Resochin
      (chloroquine), was discovered 75 years ago; for a long time, it was the drug of
      choice and to this day, it is still used in many regions of the world as a
      reliable treatment against simpler forms of malaria. In regions where it has not
      been in use against malaria tropica for quite some time due to the development of
      resistances, it has regained some of its efficacy. This review traces the
      discovery and the mechanism of action of this substance, illustrates the
      significance of malaria today, and underlines the need for controlled and
      reliable therapeutic measures.

PMID- 19593588
TI  - Physiological responses to nitrogen and sulphur addition and raised temperature
      in Sphagnum balticum.
AB  - Sphagnum, the main genus which forms boreal peat, is strongly affected by N and S
      deposition and raised temperature, but the physiological mechanisms behind the
      responses are largely unknown. We measured maximum photosynthetic rate (NP(max)),
      maximum efficiency of photosystem II [variable fluorescence (F (v))/maximum
      fluorescence yield (F (m))] and concentrations of N, C, chlorophyll and
      carotenoids as responses to N and S addition and increased temperature in
      Sphagnum balticum (a widespread species in the northern peatlands) in a 12-year
      factorial experiment. NP(max) did not differ between control (0.2 g N m(-2) year(
      1)) and high N (3.0 g N m(-2) year(-1)), but was higher in the mid N treatment
      (1.5 g N m(-2) year(-1)). N, C, carotenoids and chlorophyll concentration
      increased in shoot apices after N addition. F (v)/F (m) did not differ between N
      treatments. Increased temperature (+3.6 degrees C) had a small negative effect on
      N concentration, but had no significant effect on NP(max) or F (v)/F (m).
      Addition of 2 g S m(-2) year(-1) showed a weak negative effect on NP(max) and F
      (v)/F (m). Our results suggest a unimodal response of NP(max) to N addition and
      tissue N concentration in S. balticum, with an optimum N concentration for
      photosynthetic rate of ~13 mg N g(-1). In conclusion, high S deposition may
      reduce photosynthetic capacity in Sphagnum, but the negative effects may be
      relaxed under high N availability. We suggest that previously reported negative
      effects on Sphagnum productivity under high N deposition are not related to
      negative effects on the photosynthetic apparatus, but differences in optimum N
      concentration among Sphagnum species may affect their competitive ability under
      different N deposition regimes.

PMID- 19593589
TI  - Nephrogenic diabetes insipidus: the key element of paradoxical hyponatremia.

PMID- 19593590
TI  - The efficacy of ultrasound and dimercaptosuccinic acid scan in predicting
      vesicoureteral reflux in children below the age of 2 years with their first
      febrile urinary tract infection.
AB  - We evaluated the efficacy of dimercaptosuccinic acid (DMSA) scan and ultrasound
      (US) in comparison with voiding cystourethrography (VCUG) in predicting
      vesicoureteral reflux (VUR) in children below the age of 2 years. Medical records
      and radiologic studies of children (<2 years) suffering their first febrile
      urinary tract infection (UTI) between January 2001 and May 2007 were
      retrospectively reviewed. We evaluated the sensitivity, specificity, and positive
      and negative predictive values of US and DMSA scans in diagnosing VUR. Among 220
      children with their first febrile UTI, VUR was detected in 67 (30.4%). The
      detection rate of VUR by US was 41.7% and 86% in the low (I, II) and high grade
      (III~IV) groups, respectively. Detection rate of VUR by DMSA scan was 37.5% and
      88.4% in the low and high grade groups, respectively. Combining US and DMSA scan,
      we found that the detection rate of high grade VUR was 95.3% and that of low
      grade was 62.5%. During follow up, most of the low grade VURs with normal DMSA
      and US scans resolved or were downgraded. Most high grade VURs could be detected
      by US and DMSA scan, but the prediction rate was not as high in low grade VURs.
      However, we can anticipate spontaneous improvement without complications in
      patients with either low or high grade reflux and negative findings on US and
      DMSA scan.

PMID- 19593591
TI  - Routine assessment of social difficulties in cancer patients: are we opening
      Pandora's box?
AB  - GOALS OF WORK: Living with cancer impacts on the social aspects of the lives of
      the patient and their families, causing problems that can remain undetected. The
      Social Difficulties Inventory (SDI) has been shown as an effective screening
      tool, but concerns exist that detecting more problems may increase the workload
      for clinic staff and related services. The aim of this analysis is to assess the
      level of unmet need for social difficulties and to identify any potential
      increase in required interventions that may occur as a result of detailed
      assessment. PATIENTS AND METHODS: A previous cross-sectional interview study was
      conducted to establish the clinical utility of the SDI. Adult patients were
      recruited from oncology, haematology and chest medicine clinics. They completed
      the SDI and a semi-structured interview by a social worker, who was blind to the
      SDI results. With participant agreement, interventions were made for the detected
      problems. This paper reports on a secondary descriptive analysis of intervention
      data, which was performed to examine the details of the interventions and
      referral patterns. MAIN RESULTS: No intervention was necessary for 108 (59%) of
      patients, 42 (23%) received information, 33 (15%) were referred to another
      service and five (3%) received both information and a referral. Most information
      was provided about holiday insurance. The majority of referrals were made to
      Social Work (55% of all referrals) with the main reason being related to benefits
      or finances. CONCLUSIONS: Increased referral rate was observed following a social
      work interview, when comparing with local audit data. However, the majority of
      needs could be met by increasing accessibility of information.

PMID- 19593592
TI  - Molecular analysis of the VP7 gene of pheasant rotaviruses identifies a new
      genotype, designated G23.
AB  - Rotavirus-associated enteritis has been reported in pheasants, but there is no
      information on the genetic/antigenic features of pheasant rotaviruses. In this
      study, we sequenced the VP7-encoding genome segment of three pheasant rotavirus
      strains detected during 2008 in Hungary. The full-length genome segment was 1,070
      bp long, while the open reading frame was predicted to encode a 330-aa-long
      protein. The nucleotide sequence identities among the three pheasant rotavirus
      strains were high (> or =94%), whereas the range of nucleotide sequence
      identities to other avian and mammalian rotavirus VP7 genes fell between 68 and
      73% and between 60 and 66%, respectively. Our findings indicate that these
      Hungarian pheasant rotaviruses need to be considered representatives of a new VP7
      genotype specificity, designated G23.

PMID- 19593593
TI  - Post-exercise carbohydrate plus whey protein hydrolysates supplementation
      increases skeletal muscle glycogen level in rats.
AB  - Recent studies showed that a combination of carbohydrate and protein was more
      effective than carbohydrate alone for replenishing muscle glycogen after
      exercise. However, it remains to be unclear whether the source or degree of
      hydrolysis of dietary protein influences post-exercise glycogen accumulation. The
      aim of this study was to compare the effect of dietary protein type on glycogen
      levels in the post-exercise phase, and to investigate the effects of post
      exercise carbohydrate and protein supplementation on phosphorylated enzymes of
      Akt/PKB and atypical PKCs. Male Sprague-Dawley rats, trained for 3 days, swam
      with a 2% load of body weight for 4 h to deplete skeletal muscle glycogen.
      Immediately after the glycogen-depleting exercise, one group was killed, whereas
      the other groups were given either glucose or glucose plus protein (whey protein,
      whey protein hydrolysates (WPH), casein hydrolysates or branched-chain amino acid
      (BCAA) solutions. After 2 h, the rats were killed, and the triceps muscles
      quickly excised. WPH caused significant increases in skeletal muscle glycogen
      level (5.01 +/- 0.24 mg/g), compared with whey protein (4.23 +/- 0.24 mg/g), BCAA
      (3.92 +/- 0.18 mg/g) or casein hydrolysates (2.73 +/- 0.22 mg/g). Post-exercise
      ingestion of glucose plus WPH significantly increased both phosphorylated Akt/PKB
      (131%) and phosphorylated PKCzeta (154%) levels compared with glucose only. There
      was a significant positive correlation between skeletal muscle glycogen content
      and phosphorylated Akt/PKB (r = 0.674, P < 0.001) and PKCzeta (r = 0.481, P =
      0.017). Post-exercise supplementation with carbohydrate and WPH increases
      skeletal muscle glycogen recovery by activating key enzymes such as Akt/PKB and
      atypical PKCs.

PMID- 19593594
TI  - Osmotic adaptation in halotolerant yeast, Debaryomyces nepalensis NCYC 3413: role
      of osmolytes and cation transport.
AB  - Debaryomyces nepalensis NCYC 3413, a food spoiling yeast isolated from rotten
      apple, has been previously demonstrated as halotolerant yeast. In the present
      study, we assessed its growth, change in cell size, and measured the
      intracellular polyol and cations (Na(+) or K(+)) accumulated during growth in the
      absence and presence of different concentrations of salts (NaCl and KCl). Cells
      could tolerate 2 M NaCl and KCl in defined medium. Scanning electron microscopic
      results showed linear decrease in mean cell diameter with increase in medium
      salinity. Cells accumulated high amounts of K(+) during growth at high
      concentrations of KCl. However, it accumulated low amounts of Na(+) and high
      amounts of K(+) when grown in the presence of NaCl. Cells grown in the absence of
      salt showed rapid influx of Na(+)/K(+) on incubation with high salt. On
      incubation with 2 M KCl, cells grown at 2 M NaCl showed an immediate efflux of
      Na(+) and rapid uptake of K(+) and vice versa. To withstand the salt stress,
      osmotic adjustment of intracellular cation was accompanied by intracellular
      accumulation of polyol (glycerol, arabitol, and sorbitol). Based on our result,
      we hypothesize that there exists a balanced efflux and synthesis of osmolytes
      when D. nepalensis was exposed to hypoosmotic and hyperosmotic stress conditions,
      respectively. Our findings suggest that D. nepalensis is an Na(+) excluder yeast
      and it has an efficient transport system for sodium extrusion.

PMID- 19593596
TI  - Efficient conformational sampling of multiconformational cyclic molecules:
      application to 1,4,7,10,13-Pentaoxacyclopentadecane.
AB  - The result of an exhaustive search of low-energy conformers of 1,4,7,10,13
      Pentaoxacyclopentadecane is presented. The search method combines the generation
      of large number of trial conformers using local nonstochastic deformations known
      as the Conflex method, which is coupled to AMBER force field as the minimizer.
      The extent of the conformational space sampled was evaluated from the view point
      of the number of duplicates of each conformer, generation of inclusion type
      structures without considering the substrate and the spread of the allowed
      torsion angles visited during the search. It is shown that the conformational
      search is exhaustive and efficient as conformers, which the metal coordinated
      crown ether complexes adopt, were generated. Free energies using the AMBER
      structures were calculated using the model of Cramer and Truhlar. The study
      suggests that 1,4,7,10,13-Pentaoxacyclopentadecane exists as a mixture of
      conformers in solution. The results show the efficiency of the method and could
      be the method of choice in the design of synthetic macrocyclic receptors.

PMID- 19593595
TI  - NO3-/NO2- assimilation in halophilic archaea: physiological analysis, nasA and
      nasD expressions.
AB  - The haloarchaeon Haloferax mediterranei is able to assimilate nitrate or nitrite
      using the assimilatory nitrate pathway. An assimilatory nitrate reductase (Nas)
      and an assimilatory nitrite reductase (NiR) catalyze the first and second
      reactions, respectively. The genes involved in this process are transcribed as
      two messengers, one polycistronic (nasABC; nasA encodes Nas) and one
      monocistronic (nasD; codes for NiR). Here we report the Hfx mediterranei growth
      as well as the Nas and NiR activities in presence of high nitrate, nitrite and
      salt concentrations, using different approaches such as physiological experiments
      and enzymatic activities assays. The nasA and nasD expression profiles are also
      analysed by real-time quantitative PCR. The results presented reveal that the
      assimilatory nitrate/nitrite pathway in Hfx mediterranei takes place even if the
      salt concentration is higher than those usually present in the environments where
      this microorganism inhabits. This haloarchaeon grows in presence of 2 M nitrate
      or 50 mM nitrite, which are the highest nitrate and nitrite concentrations
      described from a prokaryotic microorganism. Therefore, it could be attractive for
      bioremediation applications in sewage plants where high salt, nitrate and nitrite
      concentrations are detected in wastewaters and brines.

PMID- 19593597
TI  - Evolutionary trace analysis of CYP51 family: implication for site-directed
      mutagenesis and novel antifungal drug design.
AB  - Lanosterol 14alpha-demethylase (CYP51) is an essential enzyme in the fungal life
      cycle and also an important target for the antifungal drug development. Based on
      the multiple sequence alignments of CYP51 family, an evolutionary tree of the
      CYP51 family was constructed by the evolutionary trace (ET) method. The
      identified trace residues could provide a reliable and rational guide to the
      design of CYP51 mutations and give more information about the detailed mechanism
      of substrate (drug) recognition and binding. The reliability of ET analysis to
      identify residues of functional importance was validated by the reported site
      directed mutagenesis studies of CYP51s. Several residues in the active site were
      also validated by our mutagenesis studies. Mapping the identified trace residues
      onto the active site of the modeled structure of Candida albicans CYP51 (CACYP51)
      may provide useful information for the design of novel antifungal agents.

PMID- 19593598
TI  - Characterization of two novel SETX mutations in AOA2 patients reveals aspects of
      the pathophysiological role of senataxin.
AB  - Ataxia with oculomotor apraxia (AOA) type 2 (AOA2 MIM 606002) is a recessive
      subtype of AOA characterized by cerebellar atrophy, oculomotor apraxia, early
      loss of reflexes, and peripheral neuropathy. Various mutations either in
      homozygous or compound heterozygous condition were so far identified in the
      associated gene SETX (MIM 608465). SETX encodes a large protein called senataxin
      with a DNA-RNA helicase domain and a putative N-terminus protein interaction
      domain. Here, we report the identification of two novel homozygous mutations in
      SETX gene, c.340_342delCTT (p.L114Del) and c.1669C > T (p.R557X), in two AOA2
      families. The characterization of the mutant lymphoblastoid cell lines for
      sensitivity to oxidative DNA-damaging agents indicates that the p.L114Del
      deletion confers an increased sensitivity to H2O2, camptothecin, and mitomycin C,
      previously found to induce death in lymphoblasts harbouring other SETX mutations;
      the cells carrying the nonsense mutation display instead values within the normal
      range. Further analysis of a neuronal cell model SKNBE, transfected with the
      mutant senataxin proteins, reveals increased sensitivity also to staurosporine
      and excitotoxicity associated with the p.L114Del mutant only. We also demonstrate
      that the sensitizing effect of p.L114Del on apoptosis can be reversed by
      senataxin silencing. The ability of a single amino acid deletion to sensitize
      cells to death by different agents, compared to the lack of effect of a whole
      protein deletion, seems to exclude a protective role played by the native protein
      while suggesting that a specific mutation confers to the protein the ability to
      enhance the toxic effect of various cell damaging agents.

PMID- 19593599
TI  - Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A
      multicenter retrospective study.
AB  - Psychiatric manifestations are relatively common in systemic lupus erythematosus
      (SLE) patients. Since there are factors causing psychiatric manifestations other
      than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous
      studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE
      patients with neuropsychiatric manifestation. The current studies were therefore
      designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter
      retrospective study was performed with 45 SLE patients who showed psychiatric
      manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to
      causes other than SLE (non-LP) was confirmed by retrospective review of the
      clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the
      retrospective study. Receiver operating characteristic curve analysis revealed
      that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5%
      and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results
      indicate that CSF IL-6 might be an effective measure in diagnosing LP, although
      exclusion of infectious meningoencephalitis and cerebrovascular accident is
      necessary.

PMID- 19593601
TI  - Representational insight in pigeons: comparing subjects with and without real
      life experience.
AB  - Understanding the relation between objects and their pictures at a level beyond
      mere feature discrimination is by no means a trivial cognitive ability, and
      support of this is still weak in nonhuman species. Here, we report evidence of
      representational insight in pigeons. Responding to pictures of human body parts
      was compared in birds that had extensive pre-experience with live humans and in
      birds that had never seen any human heads. In a two-alternative forced-choice
      procedure the pigeons were trained to discriminate between pictures of either
      handless or headless humans and nonhumans. On test, the birds had to choose (i)
      between body parts they had already seen in training and the parts that had been
      missing, (ii) between previously seen parts and arbitrary skin patches, and (iii)
      between previously missing parts and skin patches. Only the pigeons that lacked
      experience with real heads and were trained with pictures of headless humans
      failed to show a significant preference for pictures of missing parts (i.e.,
      heads) over arbitrary skin patches. This demonstrates the importance of
      individual experience with the real 3D-referents of pictures for classification
      of the latter and is thereby evidence of representational insight.

PMID- 19593600
TI  - Syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis
      (PFAPA) in siblings.
AB  - PFAPA syndrome is characterized by episodes of periodic fever, aphthous
      stomatitis, pharyngitis, and cervical adenitis. PFAPA syndrome usually begins in
      children under 5 years old and normally has self-resolution. The etiology of
      PFAPA syndrome remains unknown. In this paper, we report the cases of two
      different families with siblings with PFAPA syndrome: two sisters and two
      brothers. To our knowledge, this is the first report of siblings with PFAPA
      syndrome.

PMID- 19593602
TI  - A three-dimensional evaluation of microleakage of class V cavities prepared by
      the very short pulse mode of the erbium:yttrium-aluminium-garnet laser.
AB  - The aim of this study was to evaluate microleakage along resin restoration in
      cavities prepared with an erbium:yttrium-aluminium-garnet (Er:YAG) laser, with
      and without acid etching, and to compare it with that in diamond-drilled
      cavities. Thirty intact molars were divided into three equal groups. In the teeth
      in group I, class V cavities were prepared with a diamond drill. Cavities in
      groups II and III were prepared with an Er:YAG laser (400 mJ/15 Hz for enamel and
      250 mJ/10 Hz for dentine). The cavities in groups I and II were acid-etched and
      adhesive and flowable composite were applied to all cavities. The specimens were
      first immersed in dye for 24 h and then in 5% nitric acid for 72 h for softening.
      The fillings were extracted and photographed through a dissecting microscope. The
      leakage area was measured with specially designed software. The Kruskal-Wallis
      test showed that the best ranking was group II [mean range (m.r.) = 27.46],
      followed by group I (m.r. = 33.48) and, lastly, group III (m.r. = 45.15). The
      differences between groups I and III (P = 0.023) and between groups II and III
      were statistically significant (P = 0.080). The least microleakage was found in
      those cavities prepared by Er:YAG laser and subsequently acid-etched, whereas the
      most leakage was in the lased cavities that had not been etched; the traditional
      diamond-drilled acid-etched cavities produced medium leakage.

PMID- 19593603
TI  - Visualization of nuclear localization of transcription factors with cyan and
      green fluorescent proteins in the red alga Porphyra yezoensis.
AB  - Transcription factors play a central role in expression of genomic information in
      all organisms. The objective of our study is to analyze the function of
      transcription factors in red algae. One way to analyze transcription factors in
      eukaryotic cells is to study their nuclear localization, as reported for land
      plants and green algae using fluorescent proteins. There is, however, no report
      documenting subcellular localization of transcription factors from red algae. In
      the present study, using the marine red alga Porphyra yezoensis, we confirmed for
      the first time successful expression of humanized fluorescent proteins (ZsGFP and
      ZsYFP) from a reef coral Zoanthus sp. and land plant-adapted sGFP(S65T) in
      gametophytic cells comparable to expression of AmCFP. Following molecular cloning
      and characterization of transcription factors DP-E2F-like 1 (PyDEL1),
      transcription elongation factor 1 (PyElf1) and multiprotein bridging factor 1
      (PyMBF1), we then demonstrated that ZsGFP and AmCFP can be used to visualize
      nuclear localization of PyElf1 and PyMBF1. This is the first report to perform
      visualization of subcellular localization of transcription factors as genome
      encoded proteins in red algae.

PMID- 19593604
TI  - Calcineurin plays an important role in the shell formation of pearl oyster
      (Pinctada fucata).
AB  - Calcineurin (CN) is a multifunctional protein involved in many important
      physiological processes in mammalians, but the function of CN in mollusks is
      still largely unknown. In the present study, through the shell regeneration
      system, the changes of enzymatic activity of CN were determined in the process of
      shell regeneration in pearl oyster Pinctada fucata. CN was activated immediately
      and continuously in the shell regeneration process. The speed of shell
      regeneration was measured and the ultrastructure of inner shell surface was
      observed by scanning electron microscopy after inhibiting CN by intramuscular
      injection of immunosuppresant cyclosporine A (CsA). The results showed that the
      speed of shell regeneration was delayed and the morphology of calcite and
      aragonite in the inner shell surface became abnormal when CN was inhibited by
      CsA. Meanwhile, RT-PCR analysis revealed that the expression of P. fucata BMP-2
      in mantle tissue decreased with CsA injection. In vitro secretion level of
      proteoglycans (PGs) in primary cultures of mantle cells was also decreased when
      mantle cells were exposed to CsA. Taken together, our results, for the first
      time, show that CN is involved in the shell formation through regulating the
      expression of Pf-BMP-2 in mantle tissue, which controls the secretion of PGs/GAGs
      of the mantle epithelial cells.

PMID- 19593606
TI  - Current topics and perspectives on malignant lymphoma. Introduction.

PMID- 19593605
TI  - Endoscopic treatment of third ventricular colloid cysts: a review including ten
      personal cases.
AB  - The surgical treatment of colloid cysts has been traditionally difficult with
      high rate of postoperative complications. The variety of surgical options
      reflects the technical difficulty in removing these benign lesions with low
      morbidity. Microsurgical removal has for years been considered the "gold
      standard" of treatment, with the use of either a transcortical-transventricular
      or a transcallosal approach. Neuroendoscopic management is emerging as a safe,
      effective alternative to microsurgery. The present review discusses the role of
      endoscopy in the surgical treatment of third ventricular colloid cysts focusing
      on some factors, which might influence the outcome. The results have been
      presented from the literature and supplemented by the results of treating ten
      personal cases of third ventricular colloid cysts who were operated
      endoscopically in the Neurosurgical Department, Cairo University. This study aims
      at evaluating the endoscopic approach as a surgical line of treatment in the
      management of third ventricular colloid cysts and to see if it has already become
      superior over microsurgery.

PMID- 19593608
TI  - Recent advances in the treatment of follicular lymphoma.
AB  - The success of anti-CD20 monoclonal antibody therapy for follicular lymphoma has
      encouraged efforts to identify new target molecules, and a new generation of more
      potent antibodies is now being developed, targeting either CD20 or other
      molecules. At the same time, other agents that were developed to treat other
      kinds of malignancies have turned out to be effective against this disease. In
      both treatment approaches, using either antibodies or chemical compounds, data on
      such trials are accumulating. In this mini-review these agents are introduced,
      and it is noted that clinical trials of these new agents are also ongoing in
      Japan.

PMID- 19593607
TI  - Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological,
      and genetic features.
AB  - Nasal natural killer (NK)/T-cell lymphoma (NNKTL) is a clinical illness
      characterized by progressive unrelenting ulceration and necrosis of the nasal
      cavity and midline facial tissues. Histological features of the lymphoma include
      angiocentric and polymorphous lymphoreticular infiltrates, called polymorphic
      reticulosis. Surface antigens and the NK-cell marker, CD56, as well as pan-T
      antigen CD2, cytoplasmic CD3 (CD3epsilon), and CD45 are expressed in the lymphoma
      cells. The origin of the lymphoma is thought to be either NK-cell linkage without
      T-cell receptor (TCR) rearrangement or gammadeltaT-cell linkage with
      gammadeltaTCR rearrangement. Since the authors of this study first demonstrated
      the presence of Epstein Barr virus (EBV)-DNA and EBV oncogenic proteins in NNKTL,
      the lymphoma has been classified as one of the EBV-associated malignancies. The
      NNKTL cells produce interleukin (IL)-9, IL-10, and interferon-gamma-inducible
      protein-10 (IP-10), possibly due to EBV-oncogenic proteins in the lymphoma cells,
      and such cytokines take an important part in the cell proliferation and invasion,
      acting in an autocrine manner. Clinically, the serum EBV-DNA copy number is
      useful as a specific tumor marker and a predictive prognostic factor. Even in
      early clinical stages, the lymphoma shows poor prognosis caused by the rapid
      progression of the lesion into distinct organs. Our newly designed arterial
      infusion chemotherapy, from the superficial temporal artery, in combination with
      radiotherapy, has shown a favorable outcome in patients with NNKTL. In this
      article, the clinical, pathological, and virological characteristics of the
      lymphoma are reviewed, along with a report of our investigations.

PMID- 19593609
TI  - Fludarabine and melphalan conditioning with tacrolimus as GVHD prophylaxis for
      allogeneic stem cell transplant recipients is an effective reduced-intensity
      combination regimen compared to the conventional regimen.
AB  - BACKGROUND: As a reduced-intensity stem-cell transplantation (RIST) regimen, the
      combination of fludarabine and melphalan (FM) with an appropriate
      immunosuppressant reduces nonrelapse mortality (NRM). METHODS: We retrospectively
      compared the efficacy of a RIST regimen with FM with that of a conventional stem
      cell transplantation (CST) regimen. Eighty-two consecutive hematological patients
      who underwent allogeneic stem-cell transplantation (SCT) at our hospital were
      enrolled. Preparation for RIST consisted of 25 mg/m(2) fludarabine and melphalan
      70 mg/m(2). The conventional regimen employed high-dose cyclophosphamide and
      total-body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide. Graft
      versus-host disease (GVHD) prophylaxis for RIST consisted of tacrolimus alone or
      in conjunction with short-term methotrexate for unrelated donors. RESULTS: Of the
      82 patients, 42 received the conventional CST regimen (median age, 35 years) and
      40 received the RIST regimen (median age, 51 years). The probability of NRM was
      17% (7/42) in the CST group and 8% (3/40) in the RIST group. Grade II to IV GVHD
      occurred in significantly more CST patients (38%) than RIST patients (28%).
      However, the overall survival was the same in the two groups (43%). CONCLUSION:
      The RIST regimen with FM incorporating tacrolimus and methotrexate demonstrated
      low TRM incidence and moderate control of GVHD and had efficacy comparable to
      that of the CST regimen, despite the advanced age of the RIST patient group.

PMID- 19593610
TI  - Feasibility study of direct fentanyl patch introduction without prior opioid
      titration.
AB  - BACKGROUND: Opioids are key drugs for cancer pain relief, but some patients,
      especially those who have gastroenterological cancers, suffer from severe opioid
      induced bowel dysfunction (OBD), which reduces their quality of life. In order to
      achieve better pain relief, efforts to minimize OBD are required. METHODS:
      Between September 2006 and December 2007, 18 patients were enrolled in this
      feasibility study. All patients had gastroenterological cancer pain. The patients
      received direct fentanyl patch introduction starting from 12.5 microg/h, with
      additional opioid treatment for the first 12 h. Adverse events, changes of
      medications, pain scale, and patients' satisfaction scores were recorded for 9
      days after fentanyl patch introduction. RESULTS: All patients completed the
      protocol treatment without interruption by adverse events. Eight patients (44%)
      showed adverse events that were presumed to be related to the treatment. However,
      all events were grade 1 and had a minimal effect on patients' quality of life.
      According to subjective evaluation on day 9, only 4 patients (22%) mentioned that
      they had felt adverse events during the treatment course. Seventeen patients
      (94%) had pain score scale improvements evaluated on day 9. Satisfaction scores
      on days 9 and day 27 were excellent or good for all but one of the patients.
      CONCLUSION: This prospective study showed the safety and efficacy of direct
      fentanyl patch introduction in Japanese gastroenterological cancer patients, and
      the treatment had good feasibility. This model should help cancer pain management
      for patients with a high risk of features of OBD such as constipation, subileus,
      or postabdominal surgery.

PMID- 19593611
TI  - Use of totally implantable central venous access port via the basilic vein in
      patients with thoracic malignancies.
AB  - BACKGROUND: For patients with a thoracic malignancy whose peripheral veins are
      not suitable for blood access for chemotherapy, we evaluated a totally
      implantable central venous access port, in which the port is implanted in the
      ulnar side of the arm and the catheter is introduced via the basilic vein into
      the superior vena cava (TIAP-BV). METHODS: Twenty-five patients (21 with lung
      cancer, 2 with malignant pleural mesothelioma, and 2 with thymoma) receiving TIAP
      BV were included. Indications, surgical complications, and long-term
      complications were analyzed. RESULTS: Indications for TIAP-BV were: chemotherapy
      (17 patients) and chemotherapy with parenteral nutrition (8 patients). The
      following surgical complications occurred: arrhythmia due to misplacement of the
      tip of catheter (1 patient); intraoperative conversion from the left to right arm
      (2 patients); and hematoma at the implantation site (1 patient). Short-term
      problems were: death 1 week after implantation without the use of TIAP-BV (2
      patients). Long-term complications were: skin ulcer at the port site (1 patient);
      early removal of TIAP-BV because of port site infection (1 patient); catheter
      occlusion (1 patient); and venous thrombosis of basilic vein (2 patients). In the
      22 patients who did not die early or have the device withdrawn early, the median
      duration of TIAP-BV use was 7 months (range, 1 to 20 months) without any break to
      the port system, leakage of drugs, or catheter-related infections. CONCLUSION:
      TIAP-BV can be employed for long-term use for chemotherapy and parenteral
      nutrition. However, a patient's expected prognosis and infectious disease status
      at the time of implantation surgery should be considered before the surgery
      proceeds.

PMID- 19593612
TI  - Patterns of failure and influence of potential prognostic factors after surgery
      in transitional cell carcinoma of the upper urinary tract.
AB  - BACKGROUND: We investigated the long-term outcome of upper urinary tract
      transitional cell carcinoma (TCC) after surgery. METHODS: The study population
      comprised 114 surgically treated patients with upper urinary tract TCC treated at
      Jikei University Hospital between March 1990 and December 2004. All these
      patients underwent radical surgery without any type of neoadjuvant therapy.
      Patterns of failure and patient survival were compared with clinicopathological
      parameters. RESULTS: The 5- and 10-year overall survival (OAS) rates for the
      patients were 85% (95% confidence interval [CI], 81%-89%) and 76% (95% CI, 69%
      83%). To date, 19 patients (16.7%) have experienced distant or lymph node
      metastasis at a mean of 13.3 months following surgery (range, 1 to 50 months).
      The site of the primary tumor did not affect patient survival (P > 0.05). Both
      lymphovascular involvement (LVI) and positive lymph nodes were found to have poor
      prognosis in univariate analysis (P = 0.004 and P < 0.0001). Multivariate
      analysis indicated pathological stage and bladder recurrence (bladder recurrence
      being a better prognostic factor) to be independent predictors of metastasis-free
      survival, but not of OAS or cause-specific survival (CSS). CONCLUSION:
      Pathological stage and bladder recurrence were found to be the predictors of
      metastasis-free survival in this study. Further searching for reliable biomarkers
      is needed to accurately predict the prognosis of this malignancy.

PMID- 19593613
TI  - Effective treatment of the brachial plexus syndrome in breast cancer patients by
      early detection and control of loco-regional metastases with radiation or
      systemic therapy.
AB  - BACKGROUND: In breast cancer (BC) patients the brachial plexus syndrome (BPS) has
      been reported to be due to loco-regional metastases or radiation plexopathy.
      Associated arm edema is considered more suggestive of the latter. Radiation
      therapy is the only effective treatment for BPS reported. METHODS: The charts of
      all BC patients who presented to our clinic from 1982 to 2006 with homolateral
      arm pain and neurological deficits, without humerus, cervical spine, or brain
      metastases, were reviewed. RESULTS: There were 28 patients fulfilling these
      criteria for BPS. Supraclavicular, axillary or chest wall metastases developed
      synchronously with the BPS in 26 patients; in 21 they were recurrences, found 6
      94 months (median 34 months) after primary BC treatment, while in 5 others they
      were progressing inoperable primary tumors and nodes. Arm edema first occurred at
      the same time as loco-regional metastases in 19 patients. Treatment for the BPS
      was administered to 22 patients; it was directed at their locoregional
      metastases. The BPS was initially treated with radiation (8 patients) or chemo-
      or endocrine therapy (14 patients); 19 (86%) had partial or complete remission of
      pain and neurologic deficits, with an 8-month median duration. CONCLUSION: The
      BPS in BC patients is due to loco-regional metastases and is often associated
      with arm edema. Chemo- or endocrine therapy induced the remission of pain and
      deficits as frequently as radiation therapy.

PMID- 19593614
TI  - Significance of volume-reduction surgery for far-advanced gastric cancer during
      treatment with novel anticancer agents.
AB  - BACKGROUND: We retrospectively assessed the survival benefit of novel anticancer
      agents (NACA) after volume-reduction surgery for far-advanced gastric cancer
      (FAGC). METHODS: From 1995 to 2005, 41 patients with FAGC underwent chemotherapy
      after volume-reduction surgery. Those treated since 2000 who received NACA were
      referred to as group A, and those treated before 2000, who received anticancer
      agents other than NACA, were referred to as group B. In addition, 21 patients
      with unresectable gastric cancer treated since 2000 who received NACA were
      referred to as group C. We investigated the significance of volume-reduction
      surgery during treatment with NACA. RESULTS: The median survival time (MST) was
      significantly prolonged in group A (626 days) compared to group B (364 days; P =
      0.0156). Multivariate analysis showed that having one noncurative factor (NCF),
      and the use of NACA, were factors that contributed to survival time. Comparison
      between the subgroup of group A that had one NCF and the subgroup that had two or
      more NCFs revealed MSTs of 700 days and 180 days, respectively, with a
      significantly longer MST among the patients with one NCF (P = 0.0021). In
      addition, no difference from the MST of 333 days in group C was seen among the
      group A patients with two or more NCFs. CONCLUSION: The postoperative survival
      time of patients with one NCF was prolonged by the advent of NACA, but no
      significant prolongation was observed in the patients with two or more NCFs.

PMID- 19593616
TI  - National structure of radiation oncology in Japan with special reference to
      designated cancer care hospitals.
AB  - BACKGROUND: The structure of radiation oncology in designated cancer care
      hospitals in Japan was investigated in terms of equipment, personnel, patient
      load, and geographic distribution, and compared with the structure in other
      radiotherapy facilities. METHODS: The Japanese Society of Therapeutic Radiology
      and Oncology (JASTRO) conducted a questionnaire survey about the national
      structure of radiation oncology in 2005. In the current study, the structures of
      326 designated cancer care hospitals and the other 386 radiotherapy facilities in
      Japan were compared. RESULTS: Designated cancer care hospitals accounted for
      45.3% of all radiotherapy facilities. The patterns of equipment and personnel in
      designated cancer care hospitals and the other radiotherapy facilities were as
      follows: linear accelerators/facility, 1.2 and 1.0; dual-energy function, 73.1%
      and 56.3%; three-dimensional conformal radiotherapy function, 67.5% and 52.7%;
      intensity-modulated radiotherapy function, 30.0% and 13.9%; annual number of
      patients/linear accelerator, 289.7 and 175.1; (192)Ir remote-controlled
      afterloading systems, 27.6% and 8.6%; and average number of full-time equivalent
      radiation oncologists/facility, 1.4 and 0.9 (P < 0.0001). There were significant
      differences in equipment and personnel between the two types of facilities.
      Annual patient loads/full-time equivalent radiation oncologist in the designated
      cancer care hospitals and the other radiotherapy facilities were 252 and 240.
      Geographically, the number of designated cancer care hospitals was associated
      with the population, and the number of JASTRO-certified physicians was associated
      with the number of patients undergoing radiotherapy. CONCLUSION: The Japanese
      structure of radiation oncology in designated cancer care hospitals was more
      mature than that in the other radiotherapy facilities in terms of equipment,
      although a shortage of personnel still exists. The serious understaffing problem
      in radiation oncology should be corrected in the future.

PMID- 19593615
TI  - Integration of irinotecan and cisplatin with early concurrent conventional
      radiotherapy for limited-disease SCLC (LD-SCLC).
AB  - BACKGROUND: This study was conducted using irinotecan and cisplatin (IP)
      concurrently with thoracic radiation therapy to evaluate the response and
      toxicity of this protocol in the treatment of patients with limited-disease small
      cell lung cancer (LD-SCLC). METHODS: Twenty-seven chemotherapy-naive patients
      with LD-SCLC received two cycles of weekly irinotecan 60 mg/m(2) and cisplatin 60
      mg/m(2) before the initiation of the thoracic radiation therapy. RESULTS: Of the
      29 patients with LD-SCLC enrolled in the study, 27 were eligible for evaluation
      of response and toxicity. The median age was 62 years; 26 patients (90%) were
      men. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 5
      patients (17%) and 1 in 18 patients (62%). Ten patients (37%) achieved a complete
      response (CR), 14 patients (52%) achieved a partial response (PR), while 3
      patients (11%) had progressive disease (PD); one of the 3 nonresponders achieved
      a PR after commencing concurrent chemoradiotherapy; therefore, the overall
      response rate was 93%. The median survival time was 20.2 months and 1- and 2-year
      survival rates were 69% and 53.2%, respectively. The median progression-free
      survival (PFS) was 11.8 months, and 1- and 2-year PFS times were 52% and 34.1%,
      respectively. Neutropenia was the most prevalent hematological toxicity and it
      was evident as grade 3 in 14 patients (52%). Asthenia was the most prevalent
      nonhematological toxicity, in 18 patients (67%); esophagitis occurred in 15
      patients (56%). No treatment-related deaths (due to sepsis or bleeding) were
      reported in the study. CONCLUSION: Irinotecan and cisplatin is considered to be
      an effective and safe chemotherapeutic regimen when used concurrently with
      thoracic radiation therapy for the treatment of patients with LD-SCLC.

PMID- 19593617
TI  - Complete remission of multiple recurrent hepatocellular carcinomas by oral
      administration of enteric-coated tegafur/uracil in a patient with huge
      hepatocellular carcinoma extending to the inferior vena cava after hepatic
      resection: analysis of mRNA expression of fluoropyrimidine metabolism enzymes in
      the primary tumor.
AB  - We herein report the complete remission of multiple recurrent hepatocellular
      carcinomas (HCCs) by the oral administration of tegafur/uracil (UFT) alone. A 56
      year-old Japanese man with two huge HCCs was admitted and underwent hepatic
      resection. Intraoperative ultrasonography revealed that the tumor thrombus
      extended to the inferior vena cava (IVC) with a small tumor in the left hepatic
      lobe. Right trisectionectomy of the liver, removal of the tumor thrombus in the
      IVC, and partial resection of the left lobe were performed. Microscopic
      examination revealed that the larger tumor was moderately to poorly
      differentiated HCC and the smaller tumor was well-differentiated HCC. The small
      tumor in the left lobe was diagnosed as an intrahepatic metastasis of the larger
      tumor. Two months after the surgery, computed tomography (CT) revealed multiple
      HCC recurrences in the remnant liver, but complete remission was achieved by the
      administration of UFT alone. To clarify the reason for the good response of the
      recurrent HCC to UFT, the mRNA expression level of several fluoropyrimidine
      metabolism enzymes was measured in resected specimens. A lower expression of
      thymidine phosphorylase (TP) might explain the good response to UFT. The patient
      is alive without intra- or extrahepatic recurrence more than 6 years after the
      hepatic resection.

PMID- 19593618
TI  - Synchronous bilateral breast cancer in a male patient following hormone therapy
      for prostate cancer.
AB  - We report an unusual case of bilateral, synchronous breast cancer in a male
      patient who had a history of estrogen therapy for prostate cancer. A 64-year-old
      Japanese man was diagnosed with T1N0M0 prostate cancer and received a total
      prostatectomy. Twenty months after the resection, the patient developed multiple
      bone metastases, and received radiation therapy, systemic chemotherapy, and
      hormone therapy for 15 months. After completing this treatment, he was diagnosed
      with T1N0M0 primary breast cancer in his left breast and underwent a modified
      mastectomy. Five months after the mastectomy he received systemic chemotherapy
      followed by estrogen therapy because of the progression of prostate cancer. Three
      months after this treatment, he was diagnosed with T1N0M0 primary breast cancer
      in his right breast. To the best of our knowledge, this is a rare case of
      synchronous bilateral male breast cancer following hormone therapy for prostate
      cancer.

PMID- 19593619
TI  - Serous adenocarcinoma of the retroperitoneum, as a type of multifocal mullerian
      carcinoma.
AB  - Primary retroperitoneal serous adenocarcinoma is an extremely rare clinical
      entity, with only five cases previously reported. We describe a 66-year-old woman
      with serous adenocarcinoma arising from the retroperitoneum, adhesive to the
      ileocecum. On MRI, the tumor was 17 x 10 x 6 cm in size and monocystic. The tumor
      cells were positive for CA125, estrogen receptor, and Wilms tumor 1, and were
      differentiated from enterogenic cyst by the presence of cytokeratin 7 (+), and
      the absence of cytokeratin 20 (-). Simultaneously, uterine adnexal serous
      adenocarcinoma was detected. The volume of the retroperitoneal tumor was 14 times
      larger than that of the uterine adnexal tumor. We suggest the possibility that
      the retroperitoneal cancer arose as a primary cancer from rests of the mullerian
      epithelium synchronously with the uterine adnexal cancer. The patient had been
      taking conjugated estrogen for 10 years, suggesting that long-term estrogen
      stimulation may have contributed to the progression of the tumors.

PMID- 19593620
TI  - Four cases of advanced renal cell carcinoma with pancreatic metastasis
      successfully treated with radiation therapy.
AB  - We report four patients with pancreatic metastasis of renal cell carcinoma who
      were successfully treated with radiation therapy. The patients were one woman and
      three men with a median age of 55 years (range, 49 to 62 years) who underwent
      radical nephrectomy for primary renal cell carcinoma. The median interval from
      nephrectomy to the diagnosis of pancreatic metastasis was 129 months (range, 54
      to 176 months). Two patients experienced melanorrhea and the other two were
      asymptomatic and diagnosed during standard follow up. In each patient, a total of
      50 Gy in 2-Gy fractions over 5 weeks was prescribed, without any adverse events.
      All patients remain alive with a median follow up of 31 months (range, 11 to 81
      months).

PMID- 19593621
TI  - Gastrointestinal stromal tumor of the stomach with extremely slow-growing
      hematogenous metastasis.
AB  - A 67-year-old woman underwent resection of a gastric tumor and a synchronous
      metastatic lesion of the liver in 1991. Histopathologically, both the primary and
      metastatic tumors were diagnosed as leiomyosarcoma. Four years after the initial
      resection, another liver metastasis was detected in the caudate lobe, and a
      partial hepatectomy was performed. Multiple bilateral lung metastases were
      identified 7 years later and one was resected. Immunohistochemically, tissues
      from both the primary and metastatic sites were positive for KIT and CD34, and a
      c-kit gene mutation was found in the resected lung lesion. The remaining lung
      metastases responded to treatment with imatinib mesylate, but the treatment was
      discontinued because of toxicity. The patient remains under observation and the
      lung lesions have not progressed. At present she has no symptoms, and she has had
      no further recurrences in the past 3 years. This case is extremely unusual; a
      slowly progressing gastrointestinal stromal tumor over the course of 17 years
      from the initial diagnosis, with hematogenous metastases at multiple sites.

PMID- 19593622
TI  - Combination chemotherapy with cisplatin and gemcitabine in malignant peritoneal
      mesothelioma.
AB  - Malignant peritoneal mesothelioma is a rare neoplasm with a rapidly fatal course.
      The response of this disease to treatment is poor because it tends to be advanced
      at diagnosis and tends to have inherent resistance to chemotherapeutic treatment.
      We describe three patients with malignant peritoneal mesothelioma who received
      combination chemotherapy with cisplatin and gemcitabine. After a
      histopathological diagnosis of epithelial-type malignant peritoneal mesothelioma,
      all patients underwent systemic chemotherapy because of the advanced disease
      stage. Moreover, one patient would have been at high risk of cardiac events,
      because of congenital heart malformation if complete surgical resection had been
      performed. This chemotherapy achieved a partial response in two patients, but had
      no effect in one. Combination chemotherapy with cisplatin and gemcitabine may
      prove to be one of the recommended treatments for patients with malignant
      peritoneal mesothelioma in the near future.

PMID- 19593623
TI  - Brain metastasis of a papillary renal cell carcinoma, identified as type 2.
AB  - Papillary renal cell carcinomas (PRCCs) tend to metastasize to lymph nodes, while
      metastasis to the brain is extremely rare. We report the case of a man who had a
      brain metastasis of PRCC type 2. He was brought to our hospital due to the sudden
      onset of convulsions. Diagnostic imaging studies showed a metastatic brain tumor
      in the left parietal lobe, and a primary renal tumor in the right kidney, with
      paraaortal lymph node metastases. An excision of brain tumor was performed. The
      brain tumor had a papillary structure with eosinophilic cytoplasm. Five weeks
      later nephrectomy was carried out. Histological analysis of the nephrectomy
      specimen revealed the same papillary structure, which was compatible with PRCC
      type 2.

PMID- 19593624
TI  - Reduction of an incarcerated, prolapsed ileostomy with the assistance of sugar as
      a desiccant.
AB  - Prolapse is a well-described complication after ileostomy or colostomy, and is
      typically asymptomatic and easily reduced. Acute incarceration of a prolapsed
      stoma is a rare event, however. A patient presented with an incarcerated,
      prolapsed ileostomy causing small bowel obstruction and stomal ischemia.
      Successful reduction was performed with the assistance of sugar as a desiccant.
      Incarceration of a prolapsed ileostomy is highly atypical, but can be approached
      in a similar manner to an incarcerated rectal prolapse. Successful reduction can
      prevent an emergent operation, allowing for medical optimization and elective
      surgical treatment if necessary.

PMID- 19593625
TI  - Partial clustering prevents global crystallization in a binary 2D colloidal glass
      former.
AB  - A mixture of two types of super-paramagnetic colloidal particles with long-range
      dipolar interaction is confined by gravity to the flat interface of a hanging
      water droplet. The particles are observed by video microscopy and the dipolar
      interaction strength is controlled via an external magnetic field. The system is
      a model system to study the glass transition in 2D, and it exhibits partial
      clustering of the small particles (N. Hoffmann et al., Phys. Rev. Lett. 97,
      078301 (2006)). This clustering is strongly dependent on the relative
      concentration [Formula: see text] of big and small particles. However, changing
      the interaction strength [Formula: see text] reveals that the clustering does not
      depend on the interaction strength. The partial clustering scenario is quantified
      using Minkowski functionals and partial structure factors. Evidence that partial
      clustering prevents global crystallization is discussed.

PMID- 19593627
TI  - BMI and Spanish labour status: evidence by gender from the city of Barcelona.
AB  - The purpose of this study was to analyse whether BMI has any consequence on being
      employed or not in a specific Spanish labour market (those living in the city of
      Barcelona). Self-reported data were corrected by means of specific conversion
      formulas. Additionally, participants were questioned about making use of an IV
      procedure (gap between individual BMI score and the average value of those either
      with the same attained educational level by gender, or living in the same
      district). Irrespective of the strategy applied, the results point to the
      presence of BMI effects on labour market status exclusively for women,
      specifically those up to 45 years old.

PMID- 19593626
TI  - A Brownian energy depot model of the basilar membrane oscillation with a braking
      mechanism.
AB  - High auditory sensitivity, sharp frequency selectivity, and spontaneous
      otoacoustic emissions are signatures of active amplification of the cochlea. The
      human ear can also detect very large amplitude sounds without being damaged, as
      long as the exposed time is not too long. The outer hair cells are believed to be
      the best candidate for the active force generator of the mammalian cochlea. In
      this paper, we propose a new model for the basilar membrane oscillation which
      describes both an active and a protective mechanism by employing an energy depot
      concept and a critical velocity of the basilar membrane. The compressive response
      of the basilar membrane at the characteristic frequency and the dynamic response
      to the stimulation are consistent with the experimental results. Although our
      model displays a Hopf bifurcation, our braking mechanism results in a hyper
      compressive response to intense stimuli which is not generically observed near a
      Hopf bifurcation. Asymmetry seen in experimental recordings between the onset and
      the offset of the basilar membrane response to a sound burst is also observed in
      this model.

PMID- 19593628
TI  - Private expenditure and the role of private health insurance in Greece: status
      quo and future trends.
AB  - The health care system in Greece is financed in almost equal proportions by
      public and private sources. Private expenditure, consists mostly of out-of-pocket
      and under-the-table payments. Such payments strongly suggest dissatisfaction with
      the public system, due to under financing during the last 25 years. This gap has
      been filled rapidly by the private sector. From this point of view, one might
      suggest that the flourishing development of private provision may lead in turn to
      a corresponding growth in private health insurance (PHI). This paper aims to
      examine the role of PHI in Greece, to identify the factors influencing its
      development, and to make some suggestions about future policies and trends. In
      the decade of 1985-1995 PHI show increasing activity, reflecting the intention of
      some citizens to seek health insurance solutions in the form of supplementary
      cover in order to ensure faster access, better quality of services, and increased
      consumer choice. The benefits include programs covering hospital expenses, cash
      benefits, outpatient care expenses, disability income insurance, as well as
      limited managed care programs. However, despite recent interest, PHI coverage
      remains low in Greece compared to other EU countries. Economic, social and
      cultural factors such as low average household income, high unemployment,
      obligatory and full coverage by social insurance, lead to reluctance to pay for
      second-tier insurance. Instead, there is a preference to pay a doctor or hospital
      directly even in the form of under-the-table payments (which are remarkably high
      in Greece), when the need arises. There are also factors endogenous to the PHI
      industry, related to market policies, low organisational capacity, cream
      skimming, and the absence of insurance products meeting consumer requirements,
      which explain the relatively low state of development of PHI in Greece.

PMID- 19593629
TI  - Health insurance in Croatia: dynamics and politics of balancing revenues and
      expenditures.
AB  - Since 2002, the Croatian social health insurance system has undergone substantial
      reforms, initiated for the most part with the aim of addressing the perpetual
      financial deficits of the state health insurance fund. While the reforms focussed
      heavily on increasing the inflow of private funds into the health care system,
      underlying inefficiencies contributing significantly to poor financial
      performance have been largely ignored. Furthermore, contrary to demographic
      trends and developments in social health insurance schemes in other countries,
      funding health care became even more dependent on its main collection mechanism
      payroll tax-and consequently on the employment ratio and wage level. Little
      effort has been made to diversify the revenue base or to increase the efficiency
      of revenue collection. Like other countries, Croatia is facing difficulties in
      adjusting its 'Bismarck' system to its changing demographic and socioeconomic
      context. Instead of targetting a comprehensive effort at improving revenue
      collection and limitating unnecessary expenditure and system inefficiencies,
      simplified approaches to balance the budget have been implemented at a high price
      to users and with limited effect. As a result, the Croatian health insurance
      system now offers a lower level of financial protection, while still facing the
      problem of spending more than can be collected through the current mix of revenue
      collection mechanisms. The authors suggest that, in order to meet the
      sustainability requirement of the health financing system, measures affecting
      both revenue and expenditure should be considered and implemented. On the revenue
      collection side, the Croatian government must make further efforts to improve
      collection from the informally employed to broaden the base of contributing
      members; equally important is the diversification of revenue sources by
      increasing transfers from general taxation revenues. On the expenditure side,
      exploring inefficiencies of the delivery system can be delayed no longer, and the
      introduction of effective cost-control mechanisms and financial discipline would
      seem to be unavoidable.

PMID- 19593630
TI  - Developments in autonomic research: a review of the latest literature.
AB  - Small-diameter afferents do not just subserve pain and temperature sensibilities,
      important for protection of the body though they are: there is a system of low
      threshold unmyelinated afferents that respond to light stroking (C-tactile
      afferents) and they are believed to subserve the affective components of touch.
      Patients with large-fibre sensory neuropathies exhibit skin sympathetic responses
      to stroking, and report the stimuli as feeling pleasant. Moreover, the posterior
      insula is activated. Patients with small-diameter sensory neuropathies,
      specifically those with congenital insensitivity to pain, suffer from cumulative
      injuries that can lead to joint degeneration. There is evidence that the
      nociceptive (and sympathetic) axons die because nerve growth factor is not being
      produced by the target tissues; patients with congenital insensitivity to pain
      have mutations in the NTRK1 gene, the gene responsible for producing the TrkA
      receptor, but there is also evidence for mutations in the SCN9A gene, which codes
      for a specific subunit of the voltage-gated sodium channel. Specific mutations,
      leading to clusters of cases of congenital insensitivity to pain, have been found
      in several geographical locations, with several genetic mutations having been
      documented. Interestingly, even patients with congenital insensitivity to pain,
      despite having never experienced pain, can still empathise with the pain in
      others-we do not need to feel pain in order to empathise, but we do need to feel
      pain in order to ensure that our body looks after itself.

PMID- 19593631
TI  - Synthesis of fatty acid esters and diacylglycerols at elevated temperatures by
      alkalithermophilic lipases from Thermosyntropha lipolytica.
AB  - LipA and LipB of Thermosyntropha lipolytica DSM 11003 as previously published are
      the most alkalithermophilic (pH(opt) (25 degrees C) = 9.4-9.6, T(opt) = 96
      degrees C) and thermostable (T (1/2) (24 h) = 74-76 degrees C) lipases currently
      known. The purified enzymes were analyzed in organic solvents for their ability
      to catalyze synthesis of diacylglycerols and various alcohol fatty acids. To
      obtain 100% recovery and avoid a 40% and 50% loss of catalytic activity during
      lyophilization of purified LipA and LipB, respectively, addition of 1 mg/ml
      bovine serum albumin (BSA) and 25% polyethylene glycol (PEG400) was required.
      LipA and LipB catalyzed esterification of fatty acids and alcohols with the
      highest yields for octyl oleate (LipA) and lauryl oleate (LipB) and also
      catalyzed synthesis of 1,3-dioleoyl glycerol, 1-oleoyl-3-lauroyl glycerol, and 1
      oleoyl-3-octoyl glycerol. Isooctane was the most efficient solvent for
      esterification reactions at 85 degrees C. Similar to the positional specificity
      for the hydrolytic reaction in aqueous solutions, LipA and LipB catalyzed in
      organic solvents the synthesis of diacylglycerol with esterification of position
      1 and 3 with a yield of 62% for di-oleoyl glycerol. The reported conversion rates
      do not represent the full potential of these enzymes, since only 1/100th
      1/1,000th of the protein concentrations usually used in commercial processes were
      available. However, use of slightly increased protein concentrations confirmed
      the trend to higher yields with higher protein concentrations. The obtained
      specificity and variety of the reactions catalyzed by LipA and LipB, and their
      high thermostability allowing synthesis to occur at 90 degrees C, demonstrate
      their great potentials for industrial applications, particularly in structured
      lipid biosynthesis for substrates that are less soluble at mesobiotic
      temperatures.

PMID- 19593632
TI  - Presenting features of breast cancer differ by molecular subtype.
AB  - BACKGROUND: Gene expression profiling of breast cancers identifies distinct
      molecular subtypes that affect prognosis. Our goal was to determine whether
      presenting features of tumors differ among molecular subtypes. METHODS: Subtypes
      were classified by immunohistochemical surrogates as luminal A (estrogen receptor
      [ER] and/or progesterone receptor [PR] positive, HER-2-), luminal B (ER and/or
      PR+, HER-2+), HER-2 (ER and PR-, HER-2+), or basal (ER, PR, HER-2-). Data were
      obtained from an established, registered database of patients with invasive
      breast cancer treated at our institution between January 1998 and June 2007. A
      total of 6,072 tumors were classifiable into molecular subtypes. The chi(2) test,
      analysis of variance, and multivariate logistic regression analysis were used to
      determine associations between subtype and clinicopathologic variables. RESULTS:
      The distribution of subtypes was luminal A, 71%; luminal B, 8%; HER-2, 6%; and
      basal, 15%. Marked differences in age, tumor size, extent of lymph node
      involvement, nuclear grade, multicentric/multifocal disease, lymphovascular
      invasion (LVI), and extensive intraductal component were observed among subtypes.
      When compared with luminal A tumors, those overexpressing HER-2 (luminal B, HER
      2) were significantly more likely to manifest nodal involvement, multifocal,
      extensive intraductal component, and LVI (P < 0.0001). On multivariate analysis,
      after controlling for patient age, tumor size, LVI, and nuclear grade, HER-2
      subtype tumors were 2.0 times more likely to have four or more metastatic lymph
      nodes (P < 0.0001) and 1.6 times more likely to have multifocal disease (P <
      0.0001) compared with patients with luminal A. CONCLUSIONS: Tumor presentation
      varies among molecular subtypes; this information may be useful in selecting
      local therapy. Neoadjuvant therapy and lymph nodes evaluation before surgery or
      neoadjuvant therapy are likely to be beneficial in HER-2-overexpressing tumors.

PMID- 19593633
TI  - Overexpression of CXCR4 in primary tumor of patients with HER-2 negative breast
      cancer was predictive of a poor disease-free survival: a validation study.
AB  - BACKGROUND: Although HER-2 negative tumors are thought to be less aggressive than
      their counterpart, there is a subset that behaves poorly. The molecular mechanism
      to account for this is unknown. The chemokine receptor CXCR4 is often upregulated
      in a wide array of cancers. Using a training dataset, we previously reported that
      high CXCR4 overexpression portends a poor outcome among patients with HER-2
      negative breast tumors. This study aims to validate these findings, using our
      validation dataset. METHODS: There were 115 patients with stages I-III, HER-2
      negative breast cancers who were prospectively accrued and analyzed. CXCR4 levels
      from primary tumors were detected using Western blots, and results were
      quantified against 1 microg of HeLa cells. CXCR4 expression was defined as low
      (<6.6 fold) or high (> or =6.6 fold). Primary endpoint was cancer recurrence.
      Statistical analysis performed included Spearman correlation, Fisher exact test,
      Kaplan-Meier survival analysis, Cox proportional hazard ratio model, and log-rank
      test. RESULTS: There were 13 patients in the high (> or =6.6 fold) and 102
      patients in the low CXCR4 group (<6.6 fold). Overall survival (OS) and disease
      free survival (DFS) for the cohort was 84 and 71%, respectively. The 5-year OS
      for the high CXCR4 group was 52% and for the low CXCR4 group was 86% (P = 0.08).
      The 5-year DFS for the high CXCR4 and low CXCR4 group was 38 and 74%,
      respectively (P = 0.01). CONCLUSION: We validated that high CXCR4 overexpression
      in primary tumors of patients with HER-2 negative tumors portend a poor outcome.
      These findings should be confirmed with either a prospective clinical trial
      and/or an external validation study.

PMID- 19593634
TI  - Life history of the newly discovered Japanese tree sap mite, Hericia sanukiensis
      (Acari, Astigmata, Algophagidae).
AB  - Hericia sanukiensis (Acari, Algophagidae) is a species of tree sap mite which has
      been newly discovered in the sap flux of oak trees (Quercus acutissima). In this
      study, we have clarified the life history of H. sanukiensis at the onset of sap
      exudation in spring, overwintering deutonymphs molt to tritonymphs as their
      molting is exacerbated by the sugar contained in the tree sap, and develop to
      adulthood and reproduce. The mite colony develops as long as the sap continues to
      exude during the spring and summer. In this period, most of the protonymphs
      develop into tritonymphs directly bypassing the deutonymphal stage completely.
      Facultative deutonymphs which arise in the summer season are phoretic morphs.
      They attach to coleopteran insects, especially of the family Nitidulidae, as
      carriers by which to disperse. In autumn (when sap exudation terminates), most of
      the protonymphs molt to non-phoretic deutonymphs. In winter (without sap
      exudation), the mite colony is composed only of non-phoretic deutonymphs.

PMID- 19593635
TI  - Distinct gene mutation profiles among luminal-type and basal-type breast cancer
      cell lines.
AB  - Breast cancer has for long been recognized as a highly diverse tumor group, but
      the underlying genetic basis has been elusive. Here, we report an extensive
      molecular characterization of a collection of 41 human breast cancer cell lines.
      Protein and gene expression analyses indicated that the collection of breast
      cancer cell lines has retained most, if not all, molecular characteristics that
      are typical for clinical breast cancers. Gene mutation analyses identified 146
      oncogenic mutations among 27 well-known cancer genes, amounting to an average of
      3.6 mutations per cell line. Mutations in genes from the p53, RB and PI3K tumor
      suppressor pathways were widespread among all breast cancer cell lines. Most
      important, we have identified two gene mutation profiles that are specifically
      associated with luminal-type and basal-type breast cancer cell lines. The luminal
      mutation profile involved E-cadherin and MAP2K4 gene mutations and amplifications
      of Cyclin D1, ERBB2 and HDM2, whereas the basal mutation profile involved BRCA1,
      RB1, RAS and BRAF gene mutations and deletions of p16 and p14ARF. These subtype
      specific gene mutation profiles constitute a genetic basis for the heterogeneity
      observed among human breast cancers, providing clues for their underlying biology
      and providing guidance for targeted pharmacogenetic intervention in breast cancer
      patients.

PMID- 19593636
TI  - Antimitotic chemotherapeutics promote adhesive responses in detached and
      circulating tumor cells.
AB  - In the clinical treatment of breast cancer, antimitotic cytotoxic agents are one
      of the most commonly employed chemotherapies, owing largely to their
      antiproliferative effects on the growth and survival of adherent cells in studies
      that model primary tumor growth. Importantly, the manner in which these
      chemotherapeutics impact the metastatic process remains unclear. Furthermore,
      since dissemination of tumor cells through the systemic circulation and
      lymphatics necessitates periods of detached survival, it is equally important to
      consider how circulating tumor cells respond to such compounds. To address this
      question, we exposed both nontumorigenic and tumor-derived epithelial cell lines
      to two antitumor compounds, jasplakinolide and paclitaxel (Taxol), in a series of
      attached and detached states. We report here that jasplakinolide promoted the
      extension of microtubule-based projections and microtentacle protrusions in
      adherent and suspended cells, respectively. These protrusions were specifically
      enriched by upregulation of a stable post-translationally modified form of alpha
      tubulin, and this occurred prior to, and independently of any reductions in
      cellular viability. Microtubule stabilization with Taxol significantly enhanced
      these effects. Additionally, Taxol promoted the attachment and spreading of
      suspended tumor cell populations on extracellular matrix. While the
      antiproliferative effects of these compounds are well recognized and clinically
      valuable, our findings that microfilament and microtubule binding
      chemotherapeutics rapidly increase the mechanisms that promote endothelial
      adhesion of circulating tumor cells warrant caution to avoid inadvertently
      enhancing metastatic potential, while targeting cell division.

PMID- 19593637
TI  - E-cadherin mediates the aggregation of breast cancer cells induced by tamoxifen
      and epidermal growth factor.
AB  - In the present study, we evaluated the ability of 4-hydroxytamoxifen (OHT) and
      epidermal growth factor (EGF) to regulate homotypic adhesion in MCF7 breast
      cancer cells. Our results demonstrate that OHT and EGF activate the E-cadherin
      promoter, increase E-cadherin mRNA and protein expression and enhance homotypic
      aggregation of MCF7 cells. Interestingly, an ERalpha and EGFR cross-talk is
      involved in the E-cadherin expression by OHT and EGF, as demonstrated by knocking
      down either receptor. On the basis of our findings, the well-established cross
      talk between ERalpha and EGFR could be extended to the modulation of E-cadherin
      expression by OHT and EGF. Thus, the potential ability of tamoxifen to induce
      cell-cell aggregation may contribute to the biologic response of pharmacologic
      intervention in patients with breast cancer.

PMID- 19593638
TI  - Effects of diode laser therapy on the acellular dermal matrix.
AB  - Acellular dermal matrix (ADM) was subcutaneously implanted into calvarian skin of
      male Wistar rats (n = 40). Low-level laser (lambda 685 nm, 4 J/cm(2)) was locally
      applied in experimental group (n = 20) above the skin flap. Grafts were harvested
      at 1, 3, 7 and 14 days after surgery and underwent histological analyses. In
      treated animals, the extent of edema and the number of inflammatory cells were
      reduced (P < 0.05). The amount of collagen in graft treated with low-level laser
      were significantly higher than those of controls (P < 0.05) and were
      statistically more prominent on the 14th day after surgery. The mean count of
      fibroblasts was significantly higher in the low-laser therapy group within the
      3rd day, showing a marked influx of fibroblasts into area. In conclusion, wound
      healing of the ADM appear to be positively affected by laser therapy.

PMID- 19593640
TI  - Children's adjustment and child mental health service use: the role of parents'
      attitudes and personal service use in an upper middle class sample.
AB  - Forty-one parents and their children (20 girls and 21 boys, mean age = 4.33
      years, SD = 1.30) participated in a study to examine how parents' personal use of
      mental health services related to their attitudes toward child mental health
      services as well as to their children's adjustment. Results indicated that
      parents' attitudes and personal use of services have implications for children's
      adjustment and mental health utilization. Parents who personally used mental
      health services reported more positive help-seeking attitudes, higher level of
      help-seeking intentions, and lower stigmatization of child mental health
      services. In addition, parents who used child services in the past reported
      higher levels of internalizing (not externalizing) behaviors in their children,
      and parents' previous experience predicted child mental health service use.
      Results have implications for fostering positive attitudes and reducing stigma
      about child mental health services that may prevent parents from seeking
      professional help for their children.

PMID- 19593639
TI  - Developmental and behavioral performance of internationally adopted preschoolers:
      a pilot study.
AB  - Most international adoptees (IA) have rapid catch-up of the delays common at
      arrival. However, it is not known whether development at arrival predicts later
      abilities or school readiness. Therefore, we comprehensively evaluated language,
      fine motor, visual reception (VR), executive function (EF), attention (ATT), and
      sensory skills (SS) in IA preschoolers. We hypothesized that pre-adoptive risk
      factors, development at arrival, and the post-adoptive environment (time in day
      care) would predict developmental and behavioral outcomes and school readiness.
      37 IA (12M:25F), currently age 4-5 years and previously seen in our clinic (mean
      arrival age 12 months), were evaluated with standardized tests of development,
      language, EF, ATT, and SS, along with demographic information, parent interview,
      and review of arrival clinic records. Fine motor and VR skills at arrival ranged
      from average to very below average. At followup, most IA were average or above
      average in fine motor, VR, and language skills, but many had concerning scores
      for ATT (42%), EF (11%) and SS (48%). Arrival expressive language T scores
      (Mullen) predicted follow-up scores for expressive language (PLS-4, r = .44, p =
      .005). Arrival fine motor scores (Mullen) correlated with follow-up auditory
      comprehension scores (PLS-4, r = .47, p = .002) and inversely with inattention
      scores (Conners', r = -.48, p = .003). Arrival visual reception scores correlated
      inversely with global measures of attention (Conners' opposition r = -.45, p =
      .005, ADHD scores r = -.49, p = .002, and to a lesser extent hyperactivity r = 
      .35, p = .03). Age at arrival was a very strong predictor of many of the outcome
      measures tested, including language performance, attention regulation, executive
      function, and sensory processing. Children who spent more time in daycare had
      significantly more difficulty with emotional control (p = .005). Although IA have
      good catch-up in specific areas of development, difficulties with ATT regulation,
      EF, and sensory processing may increase the risk of later school problems.

PMID- 19593642
TI  - Assessing pollutant exposure in cultured and wild sea bass (Dicentrarchus labrax)
      from the Iberian Peninsula.
AB  - The aquaculture industry is an expanding activity, mainly due to the world
      population demand of fish. However, intensive production and the use of chemicals
      have raised environmental concerns and have questioned the quality of cultured
      fish in comparison to wild fish. Up to date, there is little information
      regarding pollutant residues in cultured stocks and the risks associated to
      consumption. Here we summarize recent data on pollutants exposure, together with
      biochemical responses in both cultured and wild sea bass (Dicentrarchus labrax)
      from the Iberian Peninsula. The obtained data highlights the use of chemicals in
      current aquaculture practices as a significant source of pollution in cultured
      fish that poses a risk to exposed individuals and may negatively impact aquatic
      ecosystems. Nonetheless, a controlled use of those chemicals and a careful
      selection of the aquaculture location can ensure relatively low and homogeneous
      levels of pollutants in cultured fish in comparison to wild specimens.

PMID- 19593641
TI  - Juvenile sea bass (Dicentrarchus labrax L.) enzymatic and non-enzymatic
      antioxidant responses following 17beta-estradiol exposure.
AB  - In the context of 17beta-estradiol (E2) as an environmental contaminant, this
      study was designed to test the hypothesis whether it can modulate antioxidant
      defenses in Dicentrarchus labrax, taking gills as the target organ. Enzymatic
      (GPX--glutathione peroxidase; CAT--catalase; GR--glutathione reductase; GST-
      glutathione S-transferase) and non-enzymatic antioxidants (NP-SH--non protein
      thiols; GSHt--total glutathione) were measured following 10-day exposure to E2 in
      two different ways: water diluted (WD, 200 or 2,000 ng/L) and intraperitoneally
      injected (i.p., 0.5 or 5 mg/kg). WD exposure caused a single alteration-CAT
      increase, whereas i.p. exposure decreased all the enzymatic antioxidants.
      Similarly, NP-SH and GSHt were reduced by i.p. exposure. Thus, different E2
      exposure routes determined clear differences on the assessed responses. Despite
      gills close contact with water, their defenses were not strongly affected in WD
      experiment. Differently, i.p. injected fish showed an overall decrease in both
      enzymatic and non-enzymatic antioxidants, more pronounced at the highest
      concentration, pointing out the E2 oxidative stress inducing potential in fish.

PMID- 19593643
TI  - Highlighting the implications of selenium dispersion from disposal of Kahota
      Industrial Triangle area, Islamabad, Pakistan using three-dimension solute
      transport model.
AB  - This study highlights the implications of selenium (Se) dispersion in groundwater
      flow regimes of Kahota Industrial Triangle area located adjacent to the Soan
      River, Islamabad. Initially, a regional groundwater 3-D flow model has been
      developed, calibrated to the known observed heads of 24 water wells, verified,
      and confirmed that convergence has actually arrived to satisfy the steady state
      condition. Later, the transient simulation was carried out adding in the known
      recharge, storage factor, porosity, and observed drawdown matched with the
      simulated drawdown that appears to fall in close agreement with a difference of
      0.25 m. As such the steady state groundwater model has facilitated to understand
      the mechanism of groundwater flow regimes in reference to the implications of
      selenium dispersion from disposal of Kahota Industrial Triangle area. Thirty-five
      water samples were collected mainly from the industrial water wells for the
      evaluation of heavy metals. Selenium being the major contributor of pollution has
      been short listed to monitor its dispersion using a solute transport model
      modular three-dimensional transport model (MT3D). Chemical parameters related to
      selenium characteristics including horizontal and vertical transverse
      dispersivity/longitudinal dispersivity, effective molecular diffusion coefficient
      and bulk density of the porous medium of aquifers have been used in MT3D
      contaminant transport model. MT3D is run for 30 years in steady state condition.
      As usual first run did not produce the exact field conditions. Therefore, the
      contaminant transport model is calibrated against the 32 values of observed
      selenium concentrations in boreholes by minor adjustments in the chemical
      parameter values. The final calibration has been achieved with residual value of
      3.88x10(-5) Kg/m3. Seven hypothetical observation wells are used to monitor the
      selenium concentrations over a long-term period of time.

PMID- 19593644
TI  - Abundances, distribution, and sources of trace metals in Nakaumi-Honjo coastal
      lagoon sediments, Japan.
AB  - Bottom sediments from Nakaumi Lagoon and the Honjo Area in southwest Japan were
      analyzed to determine their geochemical compositions and to assess potential
      impacts by comparison with sediment quality guidelines. Present-day water quality
      was also assessed. Results showed that the water quality of Nakaumi Lagoon and
      the Honjo area contrasts between their upper and lower parts. Average abundances
      of As, Pb, Zn, Cu, Ni, and Cr in the Nakaumi sediments were 12, 25, 135, 32, 21,
      and 46 ppm, respectively, compared to 10, 24, 110, 26, 20, and 38 ppm in the
      Honjo area. All averages are greater than those of the upper continental crust.
      The elevated metal concentrations are probably related to the fine-grained nature
      of the sediments, reducing bottom conditions produced by abundant organic matter
      and possibly minor non-point anthropogenic sources. Trace metal contents are
      strongly correlated with Fe2O3, suggesting that Fe oxides play a role in
      controlling abundances. Metal concentrations exceed the NYSDEC lowest effect
      level and CCME interim sediment quality guidelines that indicate moderate impact
      on aquatic organisms. Average abundances of As and Zn are comparable to the
      Coastal Ocean Sediment Database threshold, whereas maximum concentrations exceed
      that value, indicating that the concentrations of these metals are potentially
      toxic. These enrichments suggest that regular monitoring may be desirable even
      where no point sources of metal pollution exist.

PMID- 19593645
TI  - Brief report: Increasing verbal greeting initiations for a student with autism
      via a Social StoryTM intervention.
AB  - Social StoriesTM are a common intervention for addressing the social skills
      deficits individuals with autism often demonstrate. In this study, a Social Story
      intervention was used to increase acceptable verbal greeting initiations with an
      11-year-old boy who had a diagnosis of high functioning autism. A withdrawal
      design with a comparison condition examined the frequency of acceptable verbal
      greeting initiations during 5 min observation periods. Results showed no
      acceptable verbal greeting initiations during both baseline conditions, increased
      frequency of acceptable verbal greeting initiations during both intervention
      conditions, and maintenance of intervention levels of behavior with visual
      supports during the comparison condition.

PMID- 19593646
TI  - Identifying symbolic relationships in autism spectrum disorders: a deficit in the
      identification of temporal co-occurrence?
AB  - Individuals with Autism spectrum disorders (ASD) experience difficulties
      understanding the non-verbal cues conveyed by others that provide symbolic
      information about relationships between self, other, and environmental events.
      This study examined whether these difficulties reflect underlying problems in the
      identification of temporal co-occurrence, or in memorial, associative, or
      inference skills. The performance of a group of adolescents with ASD was compared
      to that of typically developing children and adolescents with learning
      difficulties on four tasks assessing these processes. The ASD group experienced
      specific difficulties when they were required to identify relationships signalled
      by the temporal co-occurrence of stimuli. These results are discussed in relation
      to theories of conceptual deduction in ASD, and a hypothesised role in social
      cognitive development for attention processes is outlined.

PMID- 19593647
TI  - Combinatorial library-based design with Basis Products.
AB  - Uncovering useful lead compounds from a vast virtual library of synthesizable
      compounds continues to be of tremendous interest to pharmaceutical researchers.
      Here we present the concept of Basis Products (BPs), a new and broadly applicable
      method for achieving efficient selections from a combinatorial library. By
      definition, Basis Products are a strategically selected subset of compounds from
      a potentially very large combinatorial library, and any compound in a
      combinatorial library can represented by its BPs. In this article we will show
      how to use BP docking scores to find the top compounds of a combinatorial
      library. Compared with the brute-force docking of an entire virtual library,
      docking with BPs are much more efficient because of the substantial size
      reduction, saving both time and resources. We will also demonstrate how BPs can
      be used for property-based combinatorial library designs. Furthermore, BPs can
      also be considered as fragments carrying chemistry knowledge, hence they can
      potentially be used in combination with any fragment-based design method.
      Therefore, BPs can be used to integrate combinatorial design with structure-based
      design and/or fragment-based design. Other potential applications of BPs include
      lead hopping and consensus core building, which we will describe briefly as well
      in this report.

PMID- 19593648
TI  - Modeling of peptides containing D-amino acids: implications on cyclization.
AB  - Cyclic peptides are therapeutically attractive due to their high bioavailability,
      potential selectivity, and scaffold novelty. Furthermore, the presence of D
      residues induces conformational preferences not followed by peptides consisting
      of naturally abundant L-residues. Therefore, comprehending how amino acids induce
      turns in peptides, subsequently facilitating cyclization, is significant in
      peptide design. Here, we performed 20-ns explicit-solvent molecular dynamics
      simulations for three diastereomeric peptides with stereochemistries: LLLLL,
      LLLDL, and LDLDL. Experimentally LLLLL and LDLDL readily cyclize, whereas LLLDL
      cyclizes in low yield. Simulations at 310 K produced conformations with inter
      terminal hydrogen bonds that correlated qualitatively with the experimental
      cyclization trend. Energies obtained for representative structures from quantum
      chemical (B3LYP/PCM/cc-pVTZ//HF/6-31G*) calculations predicted pseudo-cyclic and
      extended conformations as the most stable for LLLLL and LLLDL, respectively, in
      agreement with the experimental data. In contrast, the most stable conformer
      predicted for peptide LDLDL was not a pseudo-cyclic structure. Moreover, D
      residues preferred the experimentally less populated alpha(L) rotamers even when
      simulations were performed at a higher temperature and with strategically
      selected starting conformations. Energies calculated with molecular mechanics
      were consistent only with peptide LLLLL. Thus, the conformational preferences
      obtained for the all L: -amino acid peptide were in agreement with the
      experimental observations. Moreover, refinement of the force field is expected to
      provide far-reaching conformational sampling of peptides containing D-residues to
      further develop force field-based conformational-searching methods.

PMID- 19593649
TI  - A new method for the preparation of bioactive calcium phosphate films hybridized
      with 1alpha,25-dihydroxyvitamin D3.
AB  - The primary goal of this investigation was to develop a calcium phosphate film
      hybridized with 1alpha,25-dihydroxyvitamin D(3) for the improvement of
      osteoconductivity of bone substitutes. The hybrid films (hCaP) were prepared at
      the different concentrations of 1 x 10(-10), 1 x 10(-8), and 1 x 10(-6) M
      designated as hCaPL, hCaPM, and hCaPH, respectively. The change of the hormone
      concentration during the preparation of the hybrid films did not cause
      significant variations on the physical properties of hCaPs, i.e. surface
      morphology and roughness. On the other hand, X-ray photon spectroscope (XPS)
      measurements revealed that the concentration change affected the chemical
      composition of the hybrid films. Recruitment of osteoblast-like MG-63 cells was
      considerably improved on hCaPs compared to tissue culture plate (TCP). However,
      cell proliferation on hCaPs was substantially suppressed and inversely
      proportional to the hormone concentration used. It was observed that bone-like
      nodules which consisted of bead-like components and well-developed matrix were
      rapidly formed on hCaPs. Masson's trichrome and safranin-O stainings elucidated
      that the bead-like components were MG-63 cells. Safranin-O staining showed that
      proteoglycan was produced actively. These results indicate that the cells
      cultured on hCaPs were strongly stimulated by the hormone to produce proteoglycan
      which can be considered as an induction of premature bone formation. The number
      of the nodules was increased with hormone concentration and most pronounced at
      the hCaPH. Gene expression patterns of alkaline phosphatase (ALP), transforming
      growth factor-beta (TGF-beta), and osteopontin (OPN) were strongly modulated by
      hybridized the hormone. For ALP and OPN, gene expressions were activated earlier
      on hCaPs than untreated calcium phosphate (CaP) confirming the effect of the
      hybridization was substantial. The TGF-beta gene expression was immediately
      activated after seeding but difference between samples was not significant
      suggesting that the gene expression was modulated not by the hormone
      hybridization but by CaP itself. As a result, hybridization of 1,25(OH)(2)D(3)
      with CaP can be a potentially strong candidate to promote osteoconductivity of
      implant materials.

PMID- 19593650
TI  - Biological properties of carbon/carbon implant composites with unique
      manufacturing processes.
AB  - The goal was to manufacture carbon/carbon (C/C) composites through a unique
      procedure with improved biocompatibility and reduced debris release. C/C
      composites were prepared by chemical vapor deposition, and their biological
      properties were analyzed. With regard to mechanical properties, compressive
      strength/modulus was 219.1 MPa/9.72 GPa, flexural strength/modulus was 121.63
      MPa/21.9 GPa, and interlaminar sheer was 15.13 GPa. Biocompatibility testing
      revealed: (1) the extract liquid from the C/C composites had no effect on cell
      proliferation; (2) the extract had no impact on micronucleus frequency as
      compared with the control groups (P > 0.05); (3) in vivo, there was mild tissue
      inflammation after implantation within the first 2 weeks, but there was no
      significant difference compared with the control group (P > 0.05); (4) the
      implants were well integrated into the host tissue, and debris was limited. The
      tested samples have excellent biocompatibilities and reduced release of debris.
      The demonstrated changes in manufacturing procedures are promising.

PMID- 19593651
TI  - Effect of Ca/P ratio and milling material on the mechanochemical preparation of
      hydroxyapaptite.
AB  - The mechanochemical transformation of Ca(OH)(2)-(NH(4))(2)HPO(4) with different
      Ca/P ratios 1; 1.5; 1.67 and 1.75 was carried out for different periods of time
      from 10 min to 24 h in a horizontal vibration mill using steel and agate vials
      and balls. The phase transformations obtained at each milling stage were
      characterized by X-ray diffraction, infrared spectroscopy and transmission
      electron microscopy. Complete transformation to hydroxyapatite took place during
      the first 5 h of milling, for Ca/P ratios 1.5 to 1.7, when milling was carried
      out with steel vials and balls. The contamination was not significant for the
      periods of milling studied for both milling media.

PMID- 19593652
TI  - Evolutionary alkaline transition in human cytochrome c.
AB  - Conformational transitions in cytochrome c (cyt c) are being realized to be
      responsible for its multi-functions. Among a number of conformational transitions
      in cyt c, the alkaline transition has attracted much attention. The cDNA of human
      cyt c is cloned by RT-PCR and a high-effective expression system for human cyt c
      has been developed in this study. The equilibrium and kinetics of the alkaline
      transition of human cyt c have been systematically investigated for the first
      time, and compared with those of yeast and horse cyt c from an evolutionary
      perspective. The pK(a) value for the alkaline transition of human cyt c is
      apparently higher than that of yeast and horse. Kinetic studies suggest that it
      is increasingly difficult for the alkaline transition of cyt c from yeast, horse
      and human. Molecular modeling of human cyt c shows that the omega loop where the
      lysine residue is located apparently further away from heme in human cyt c than
      in yeast iso-1 and horse heart cyt c. These results regarding alkaline
      conformational transition provide valuable information for understanding the
      molecular basis for the biological multi-functions of cyt c.

PMID- 19593653
TI  - Response of Mythimna unipuncta males to components of the Sesamia nonagrioides
      pheromone.
AB  - Several sympatric lepidopteran species feed on maize plants, and the different
      components of their species-specific female sex pheromones may play a role in
      attracting conspecifics and/or deter heterospecific males. In this study, we
      analyzed the content of Mythimna unipuncta pheromone glands and tested the
      response of males to components of their own pheromone blend and that of Sesamia
      nonagrioides in the wind tunnel. Whole pheromone glands, and lures where (Z)-9
      hexadecenyl acetate, Z)-11-hexadecen-1-ol or (Z)-9-hexadecenyl acetate + (Z)-11
      hexadecen-1-ol were added to the major component, (Z)-11-hexadecenyl acetate,
      elicited significantly higher responses by M. unipuncta males than lures with
      main component alone, although the levels varied with concentration. In the field
      a rather different outcome was observed, as the addition of other compounds found
      in the female pheromone gland did not improve trap catch over lures with only (Z)
      11-hexadecenyl acetate. The addition of (Z)-11-hexadecenal, a compound of the S.
      nonagrioides pheromone, to (Z)-11-hexadecenyl acetate significantly reduced
      attraction of M. unipuncta males both in the wind tunnel and in the field, as
      well as the number of sympatric clover cutworm, Discestra trifolii, under field
      conditions. The addition of (Z)-9-hexadecenyl acetate, a minor component of the
      M. unipuncta pheromone blend, reduced the number of S. nonagrioides captured in
      field traps that were baited with the S. nonagrioides lure. The significance of
      such inhibition in the reproductive isolation of sympatric species that attack
      maize is discussed.

PMID- 19593654
TI  - Mechanistic aspects of quantum dot based probing of Cu (II) ions: role of
      dendrimer in sensor efficiency.
AB  - Selective quenching of luminescence of quantum dots (QDs) by Cu2+ ions vis-a-vis
      other physiologically relevant cations has been reexamined. In view of the
      contradiction regarding the mechanism, we have attempted to show why Cu2+ ions
      quench QD-luminescence by taking CdS and CdTe QDs with varying surface groups. A
      detailed study of the solvent effect and also size dependence on the observed
      luminescence has been carried out. For a 13% decrease in particle diameter (4.3
      nm -->3.7 nm), the quenching constant increased by a factor of 20. It is
      established that instead of surface ligands of QDs, conduction band potential of
      the core facilitates the photo-induced reduction of Cu (II) to Cu (I) thereby
      quenching the photoluminescence. Taking the advantage of biocompatibility of
      dendrimer and its high affinity towards Cu2+ ions, we have followed interaction
      of Cu2+-PAMAM and also dendrimer with the CdTe QDs. Nanomolar concentration of
      PAMAM dendrimer was found to quench the luminescence of CdTe QDs. In contrast,
      Cu2+-PAMAM enhanced the fluorescence of CdTe QDs and the effect has been
      attributed to the binding of Cu2+-PAMAM complex to the CdTe particle surface. The
      linear portion of the enhancement plot due to Cu2+-PAMAM can be used for
      determination of Cu2+ ions with detection limit of 70 nM.

PMID- 19593655
TI  - Using neural networks to model the behavior and decisions of gamblers, in
      particular, cyber-gamblers.
AB  - This article describes the use of neural networks (a type of artificial
      intelligence) and an empirical data sample of, inter alia, the amounts of bets
      laid and the winnings/losses made in successive games by a number of cyber
      gamblers to longitudinally model gamblers' behavior and decisions as to such bet
      amounts and the temporal trajectory of winnings/losses. The data was collected by
      videoing Texas Holdem gamblers at a cyber-gambling website. Six "persistent"
      gamblers were identified, totaling 675 games. The neural networks on average were
      able to predict bet amounts and cumulative winnings/losses in successive games
      accurately to three decimal places of the dollar. A more important conclusion is
      that the influence of a gambler's skills, strategies, and personality on his/her
      successive bet amounts and cumulative winnings/losses is almost totally reflected
      by the pattern(s) of his/her winnings/losses in the few initial games and his/her
      gambling account balance. This partially invalidates gamblers' illusions and
      fallacies that they can outperform others or even bankers. For government policy
      makers, gambling industry operators, economists, sociologists, psychiatrists, and
      psychologists, this article provides models for gamblers' behavior and decisions.
      It also explores and exemplifies the usefulness of neural networks and artificial
      intelligence at large in the research on gambling.

PMID- 19593656
TI  - "Disease-breeders" among us: deconstructing race and ethnicity as risk factors of
      immigrant ill health.
AB  - Race and ethnicity are well-established epidemiological categories that relate to
      the patients' risk of exposure and their susceptibility/resistance to disease.
      However, this association creates the notion that factors other than a personal
      identity need not be held responsible for patients' health problems. This work
      deconstructs the notion of race and ethnicity as risk factors for immigrant ill
      health, which is prevalent in current medical research and practice, by tracing
      its roots in Canadian history. The understanding that medical knowledge is
      subject to diverse historical, social, cultural and political influences can
      change the way health professionals perceive their patients as a health threat.

PMID- 19593657
TI  - Characterisation of a human liver cystathionine beta synthase mRNA sequence
      corresponding to the c.[833T>C;844_845ins68] mutation in CBS gene.
AB  - Cystathionine beta synthase (CBS) is the only reaction that removes homocysteine
      from methionine cycle and redirects it to the transsulfuration pathway. The
      c.[833T>C;844_845ins68] mutation in the CBS gene has been reported initially as
      corresponding to classic homocystinuria. Studies showing that the insertion is
      associated with very smalls amounts of the transcript in the nucleus; others
      suggest that the heterozygous and homozygous subjects are protected against
      hyperhomocysteinemia and that the insertion tends to rescue the protein function.
      The liver is the major organ which metabolizes the circulating homocysteine to
      cystathionine. We have determined the sequence of the liver mRNA corresponding to
      the CBS c.[833T>C;844_845ins68] gene. We have shown that a novel splicing event
      could account for the modification in protein and possibly in enzyme activity.

PMID- 19593659
TI  - Functional characterization of the promoter region of human TNFAIP1 gene.
AB  - Tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) is an immediate-early
      response gene of endothelium induced by TNF alpha. However, little is really
      known concerning the TNFAIP1 expression regulation. To better understand how
      TNFAIP1 expression is regulated, we functionally characterized the promoter
      region of human TNFAIP1 gene. Deletion mutation analysis, gel electrophoretic
      mobility shift, and site-directed mutagenesis assays allowed the identification
      of one functional Sp1-binding site within the human TNFAIP1 core promoter region.
      Moreover, chromatin immunoprecipitation analysis indicated that Sp1 was
      associated in vivo with the TNFAIP1 promoter. Further, Sp1 overexpression
      enhanced TNFAIP1 promoter activity. These findings suggest that Sp1 is implicated
      in the control of basal TNFAIP1 gene expression. Accordingly, Sp1 is supposed to
      be involved in the elevation of TNFAIP1 in response to TNF alpha induction, and
      thus participate in inflammation-associated angiogenesis.

PMID- 19593661
TI  - Evolution of flower shape in Plantago lanceolata.
AB  - Plantago lanceolata produces small actinomorphic (radially symmetric), wind
      pollinated flowers that have evolved from a zygomorphic, biotically pollinated
      ancestral state. To understand the developmental mechanisms that might underlie
      this change in flower shape, and associated change in pollination syndrome, we
      analyzed the role of CYC-like genes in P. lanceolata. Related zygomorphic species
      have two CYC-like genes that are expressed asymmetrically in the dorsal region of
      young floral meristems and in developing flowers, where they affect the rate of
      development of dorsal petals and stamens. Plantago has a single CYC-like gene
      (PlCYC) that is not expressed in early floral meristems and there is no apparent
      asymmetry in the pattern of PlCYC expression during later flower development.
      Thus, the evolution of actinomorphy in Plantago correlates with loss of dorsal
      specific CYC-like gene function. PlCYC is expressed in the inflorescence stem, in
      pedicels, and relatively late in stamen development, suggesting a novel role for
      PlCYC in compacting the inflorescence and retarding stamen elongation in this
      wind pollinated species.

PMID- 19593663
TI  - Cerebral malignancy presenting with post stroke depression.
AB  - The following case report highlights about a Glioblastoma presenting with
      features of post stroke depression. The neuropsychological findings though
      initially was normal but on subsequent follow up showed gross abnormalities. The
      imaging studies revealed the tumor, involving the right parietal and temporal
      lobes with midline shift and high vascularity. The patient exhibited rapid
      downhill course and died within 4 weeks of initial presentation.

PMID- 19593662
TI  - Alternative methods for sampling and preservation of photosynthetic pigments and
      tocopherols in plant material from remote locations.
AB  - Current methods for the study of pigments involve freezing in liquid nitrogen and
      storage at -80 degrees C or lyophilization until HPLC analysis. These
      requirements greatly restrict ecophysiological research in remote areas where
      such resources are hardly available. We aimed to overcome such limitations by
      developing several techniques not requiring freezing or lyophilization. Two
      species with contrasting foliar characteristics (Olea europaea and Taraxacum
      officinale) were chosen. Seven preservation methods were designed, optimized and
      tested in a field trial. These protocols were compared with a control immediately
      frozen after collection. Pigments and tocopherols were analysed by HPLC. Main
      artefacts were chlorophyll epimerization or phaeophytinization, carotenoid
      isomerization, altered de-epoxidation index and tocopherol degradation. Among all
      methods, sample desiccation in silica gel provides robust samples (pigment
      composition was unaffected by storage time or temperature) and almost unaltered
      pigment profiles, except for a shift in epoxidation state. Although liquid
      nitrogen freezing and subsequent lyophilization or freezer storage were
      preferred, when these facilities are either not available or not suitable for
      long-distance transport, desiccation with silica gel, passive extraction in
      acetone and/or storage of fresh samples in water vapour saturated atmospheres
      enable a complete pigment characterization. Silica gel is advisable for long-term
      sample conservation.

PMID- 19593660
TI  - Salvage therapy with single agent bevacizumab for recurrent glioblastoma.
AB  - A retrospective evaluation of single agent bevacizumab in adults with recurrent
      glioblastoma (GBM) with an objective of determining progression free survival
      (PFS). There is no standard therapy for recurrent GBM after failure of alkylator
      based chemotherapy. A total of 50 adults, ages 36-70 years (median 64), with
      recurrent GBM were treated. All patients had previously been treated with
      surgery, concurrent radiotherapy and temozolomide, post-radiotherapy temozolomide
      and in 34 patients, one salvage regimen (PCV: 21, cyclophosphamide: 13). A total
      of 13 patients underwent repeat surgery. Patients were treated at first or second
      recurrence with bevacizumab, once every 2 weeks, defined as a single cycle.
      Neurological evaluation was performed every 2 weeks and neuroradiographic
      assessment following the initial 2 cycles of bevacizumab and subsequently after
      every 4 cycles of bevacizumab. A total of 468 cycles of bevacizumab (median 2
      cycles; range 1-30) was administered. Bevacizumab-related toxicity included
      fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade
      3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound
      dehiscence (2; 1 grade 3). 21 patients (42%) demonstrated a partial radiographic
      response and 29 (58%) progressive disease following 1-2 cycles of bevacizumab.
      Time to tumor progression ranged from 0.5 to 15 months (median: 1.0 months).
      Survival ranged from 2 to 17 months (median: 8.5 months). 6-month and 12-month
      PFS were 42% and 22% respectively. Single agent bevacizumab demonstrated efficacy
      and acceptable toxicity in this cohort of adults with recurrent alkylator
      refractory GBM.

PMID- 19593664
TI  - Frequency and safety of switching antithrombin therapy at a regional PCI center.
AB  - The impact of switching antithrombin therapy in patients presenting with acute
      coronary syndromes (ACS) and undergoing percutaneous intervention (PCI) has
      varied in clinical trials. We sought to assess the incidence and safety of
      switching antithrombin therapy in ACS patients undergoing PCI at a regional
      medical center. All patients with ACS undergoing PCI (n = 728) during a specified
      time period in 2005 and 2007 were identified. Patients who were switched to the
      antithrombin bivalirudin were defined as the "switch" group (n = 323) and all
      others were defined as the "consistent" therapy group (n = 405). Primary
      endpoints were major adverse cardiac event (MACE) (death, MI or urgent
      revascularization), major bleeding and net adverse clinical event (NACE) (MACE or
      major bleeding). Multivariate analysis was performed to determine if switching
      antithrombotic therapy predicted primary outcomes. Among 728 patients undergoing
      PCI for ACS, 44% were switched to bivalirudin. Switch patient were more likely to
      be transfers from outside hospitals, older, female, and diabetic. Angiographic
      characteristics were similar in the two groups. Switch patients had a similar
      incidence of MACE (7 vs. 8%, P = 0.72), major bleeding (2 vs. 2%) and NACE (9 vs.
      10%, P = 0.51) when compared to those who received consistent therapy. On
      multivariate analysis, switching did not predict MACE (OR = 0.94, 95% CI = 0.53
      1.67, P = 0.84) or NACE (OR = 0.82, 95%CI = 0.48-1.41, P = 0.47). In a regional
      clinical practice of patients presenting with ACS and undergoing PCI, switching
      of antithrombin therapy to bivalirudin is a common practice and patient who are
      switched have similar outcomes compared to patients who receive consistent
      therapy.

PMID- 19593665
TI  - The risk of bacteriuria and ureteric stent colonization in immune-compromised
      patients with double J stent insertion.
AB  - PURPOSE: To evaluate the influence of diabetes mellitus (DM), chronic renal
      failure (CRF), and malignancies on the rate of bacteriuria and double J ureteric
      stent bacterial colonization. PATIENTS AND METHODS: One hundred and twenty
      patients were included in this prospective study. Midstream urine samples for
      culture were obtained before ureteric stent insertion. Patients with negative
      culture were given ciprofloxacin 500 mg orally q 12 h for 5 days as a
      prophylaxis. All the stents were removed or changed as indicated after having
      voided midstream urine sample for culture on the day of stent removal. Stents
      were sent for culture. Culture was obtained from the outer surface of the stent
      by gentle scraping with a sterile scalpel. Significant bacteriuria was defined as
      a count of colony-forming units per milliliter of urine of >10(5). RESULTS: The
      patients were between 20 and 74 years of age (mean 42.5 + or - 13) and the
      duration of stent insertion ranged between 14 and 120 days (52.5 + or - 7.2). In
      29 patients (24.2%), double J stent bacterial colonization was positive (12 males
      and 17 females). Of these patients, 27 (22.5%) had positive urine cultures (11
      males and 16 females). The most commonly isolated pathogen was Escherichia coli.
      DM, CRF, or malignancies showed a higher risk for bacteriuria and stent bacterial
      colonization. CONCLUSION: Immune-compromising diseases such as DM, CRF, and
      malignancies are proved to be risk factors for urinary tract infection and stent
      colonization in patients with ureteric stent insertion. Stent cultures are not
      needed as the same microorganisms grow in urine cultures.

PMID- 19593666
TI  - Effect of day of transfer and treatment administration on the recipient on
      pregnancy rates after equine embryo transfer.

PMID- 19593667
TI  - Association of pregnane X receptor with multidrug resistance-related protein 3
      and its role in human colon cancer chemoresistance.
AB  - BACKGROUND: Pregnane xenobiotic receptor (PXR), a ligand-activated transcription
      factor, regulates the drug metabolism and transport. Its activation can reduce
      the efficacy of antineoplastic agents. The aim of this study was to investigate
      the role of PXR and the relationship between PXR and multidrug resistance-related
      protein 3 (MRP3) in human colon cancer chemoresistance. RESULTS: The results
      showed that both the mitochondrial RNA (mRNA) and protein levels of PXR and MRP3
      were much higher in colon cancer tissues than that in nonneoplastic tissues by
      reverse transcriptase polymerase chain reaction and Western blot analysis. MRP3
      mRNA was significantly correlated with PXR mRNA in cancerous (P = 0.001) and
      nonneoplastic (P < 0.001) colon tissues with Pearson correlation test. The
      expressions of PXR, SP1, and MRP3 were markedly enhanced after rifampicin
      treatment. On the other hand, the protein level of MRP3 decreased after stable
      RNA interference of PXR. It also observed that PXR, activated by rifampicin or
      knocked down via short hairpin RNAs, could enhance or reduce cells resistance to
      the chemotherapeutic agents through 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. CONCLUSIONS: The results suggested that PXR,
      associated with MRP3, may play an important role in human colon cancer resistance
      to chemotherapeutics and SP1 may be involved in the induction of MRP3 by PXR
      activation.

PMID- 19593668
TI  - Outcome after resection of hepatic and pulmonary metastases of colorectal cancer.
AB  - INTRODUCTION: Multimodal therapies (especially surgery of metastases and
      "aggressive" chemotherapy) in patients with metastases of colorectal cancers
      (CRC) are increasingly performed and may provide long-term survival in selected
      patients with more than one location of metastases. In the current literature,
      there are only few studies with relatively low patient numbers reporting on the
      outcome after resection of both hepatic and pulmonary metastases of CRC. We
      therefore evaluated survival of patients who underwent sequential resection of
      hepatic and pulmonary metastases under potentially curative intention. MATERIAL
      AND METHODS: From 1987 until 2006, 44 patients (32% female; median age, 58 years)
      with hepatic and pulmonary CRC metastases underwent resections at both metastatic
      sites. The primary CRCs were in 50% rectal and in 50% colonic carcinomas (61%
      node positive, all with free resection margins). Metastases occurred
      synchronously (regarding primary CRC) in 32% of the patients. In 86%, liver
      resection was performed prior to pulmonary resection. The first resection of
      metastases was performed a median of 16 months after resection of the primary
      CRC; the median interval between the first and the second resection of metastases
      was 7 months. Forty-seven percent of the patients also underwent at least a third
      metastasectomy. During resection of the first and second site of metastases, free
      margins were achieved in 98% and 95%, respectively. Survival analysis was
      performed using Kaplan-Meier and Cox regression methods. RESULTS: The 5-year
      survival rates (SV) were 64% after initial surgery of CRC, 42% after the first
      resection of metastases, and 27% after the last metastasectomy. Patients with
      synchronous metastases had a 5-year SV after first metastasectomy of 43% and in
      patients with metachronous metastases of 41% (n.s.). The location of the primary
      tumor (20% 5-year SV in rectal vs. 57% in colonic cancer; p < 0.02) and the lung
      as primary site of metastatic disease (5-year SV 0% vs. 60% in patients with
      primarily hepatic metastases only; p < 0.001) significantly influenced survival
      in univariate analysis. Patients with rectal cancer had a significantly higher
      frequency of the lung as first metastatic site (46%) compared to patients with
      colonic cancer (14%; p < 0.03). Multivariate survival analysis revealed the lung
      as first metastatic site and as the sole significant independent factor for the
      outcome (p < 0.001; relative risk vs. liver first metastases 4.7). CONCLUSION: In
      selected patients with metastasized CRC resection of both hepatic and pulmonary
      metastases may improve survival rates or even provide long-term survival.
      Patients with lung as the first site of metastatic disease (either lung only or
      in combination with hepatic metastases) have a significantly worse outcome than
      patients with metastases primarily confined to the liver.

PMID- 19593669
TI  - Robotic arm-assisted UKA improves tibial component alignment: a pilot study.
AB  - The alignment of the components of unicompartmental knee arthroplasty (UKA)
      reportedly influences outcomes and durability. A novel robotic arm technology has
      been developed with the expectation that it could improve the accuracy of bone
      preparation in UKA. During the study period, we compared the postoperative
      radiographic alignment of the tibial component with the preoperatively planned
      position in 31 knees in 31 consecutive patients undergoing UKA using robotic arm
      assisted bone preparation and in 27 consecutive patients who underwent unilateral
      UKA using conventional manual instrumentation to determine the error of bone
      preparation and variance with each technique. Radiographically, the root mean
      square error of the posterior tibial slope was 3.1 degrees when using manual
      techniques compared with 1.9 degrees when using robotic arm assistance for bone
      preparation. In addition, the variance using manual instruments was 2.6 times
      greater than the robotically guided procedures. In the coronal plane, the average
      error was 2.7 degrees +/- 2.1 degrees more varus of the tibial component relative
      to the mechanical axis of the tibia using manual instruments compared with 0.2
      degrees +/- 1.8 degrees with robotic technology, and the varus/valgus root mean
      square error was 3.4 degrees manually compared with 1.8 degrees robotically.
      Further study will be necessary to determine whether a reduction in alignment
      errors of these magnitudes will ultimately influence implant function or
      survival. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 19593670
TI  - An oxidant- and solvent-stable protease produced by Bacillus cereus SV1:
      application in the deproteinization of shrimp wastes and as a laundry detergent
      additive.
AB  - The current increase in amount of shrimp wastes produced by the shrimp industry
      has led to the need in finding new methods for shrimp wastes disposal. In this
      study, an extracellular organic solvent- and oxidant-stable metalloprotease was
      produced by Bacillus cereus SV1. Maximum protease activity (5,900 U/mL) was
      obtained when the strain was grown in medium containing 40 g/L shrimp wastes
      powder as a sole carbon source. The optimum pH, optimum temperature, pH
      stability, and thermal stability of the crude enzyme preparation were pH 8.0, 60
      degrees C, pH 6-9.5, and <55 degrees C, respectively. The crude protease was
      extremely stable toward several organic solvents. No loss of activity was
      observed even after 60 days of incubation at 30 degrees C in the presence of 50%
      (v/v) dimethyl sulfoxide and ethyl ether; the enzyme retained more than 70% of
      its original activity in the presence of ethanol and N,N-dimethylformamide. The
      protease showed high stability toward anionic (SDS) and non-ionic (Tween 80,
      Tween 20, and Triton X-100) surfactants. Interestingly, the activity of the
      enzyme was significantly enhanced by oxidizing agents. In addition, the enzyme
      showed excellent compatibility with some commercial liquid detergents. The
      protease of B. cereus SV1, produced under the optimal culture conditions, was
      tested for shrimp waste deproteinization in the preparation of chitin. The
      protein removal with a ratio E/S of 20 was about 88%. The novelties of the SV1
      protease include its high stability to organic solvents and surfactants. These
      unique properties make it an ideal choice for application in detergent
      formulations and enzymatic peptide synthesis. In addition, the enzyme may find
      potential applications in the deproteinization of shrimp wastes to produce
      chitin.

PMID- 19593671
TI  - Expression of a chitinase gene from Metarhizium anisopliae in tobacco plants
      confers resistance against Rhizoctonia solani.
AB  - The chit1 gene from the entomopathogenic fungus Metarhizium anisopliae, encoding
      the endochitinase CHIT42, was placed under the control of the CaMV 35S promoter,
      and the resulting construct was transferred to tobacco. Seventeen kanamycin
      resistant transgenic lines were recovered, and the presence of the transgene was
      confirmed by polymerase chain reactions and Southern blot hybridization. The
      number of chit1 copies was determined to be varying from one to four. Copy number
      had observable effects neither on plant growth nor development. Substantial
      heterogeneity concerning production of the recombinant chitinase, and both
      general and specific chitinolytic activities were detected in leaf extracts from
      primary transformants. The highest chitinase activities were found in plants
      harboring two copies of chit1 inserts at different loci. Progeny derived from
      self-pollination of the primary transgenics revealed a stable inheritance
      pattern, with transgene segregation following a mendelian dihybrid ratio. Two
      selected plants expressing high levels of CHIT42 were consistently resistant to
      the soilborne pathogen Rhizoctonia solani, suggesting a direct relationship
      between enzyme activity and reduction of foliar area affected by fungal lesions.
      To date, this is the first report of resistance to fungal attack in plants
      mediated by a recombinant chitinase from an entomopathogenic and acaricide
      fungus.

PMID- 19593672
TI  - In silico and experimental studies of concanavalin A: insights into its
      antiproliferative activity and apoptotic mechanism.
AB  - Concanavalin A (ConA), a mannose/glucose-binding legume lectin, has been reported
      to induce tumor cell death via a mitochondria-mediated autophagic pathway;
      however, the precise mechanism by which induces cell death remains to be
      discovered. In this study, we simulated the three-dimensional structure of ConA
      monomer, its dimer, and tetramer forms and reported its molecular dynamics
      simulations and phylogenetic analysis. Subsequently, we showed that ConA
      possessed remarkable antiproliferative effects on HepG2 cells. Further data
      showed that there was a link among its hemagglutinating, sugar-binding, and
      antiproliferative activities. In addition, we found that ConA induced apoptosis
      in HepG2 cells. Then, we demonstrated that the treatment of ConA caused
      mitochondrial transmembrane potential (MMP) collapse, cytochrome c release, and
      activation of caspase. In conclusion, we demonstrate that there is a positive
      correlation between carbohydrate-binding activity and antiproliferative activity
      of ConA. In addition, we confirm that ConA induces HepG2 cell death through a
      mitochondrial apoptotic pathway.

PMID- 19593673
TI  - Altered expression of proliferation-inducing and proliferation-inhibiting genes
      might contribute to acquired doxorubicin resistance in breast cancer cells.
AB  - This study was designed to investigate the molecular changes that may develop
      during exposure of breast cancer cells to anticancer agents and that may lead to
      acquired resistance. We used two breast cancer cell lines, a parental (MCF7/WT)
      and a doxorubicin-resistant (MCF7/DOX) one. Cell survival, cell cycle
      distribution and RT-PCR expression level of genes involved in DNA damage
      response, MDR1, GST and TOPOIIalpha were measured. MCF7/DOX cells were five-fold
      more resistant to doxorubicin (DOX) than the MCF7/WT cells. DOX treatment causes
      arrest of MCF7/DOX cells in G1 and G2 phases of cell cycle whereas MCF7/WT cells
      were arrested in S-phase. The molecular changes in both cell lines due to DOX
      treatment could be classified into: (1) the basal level of p53, p21, BRCA1, GST
      and TOPOIIalpha mRNA was higher in MCF7/DOX than MCF7/WT. During DOX treatment,
      the expression level of these genes decreased in both cell lines but the rate of
      down-regulation was faster in MCF7/WT than MCF7/DOX cells. (2) The expression
      level of MDR1 was the same in both cell lines but 48 and 72 h of drug treatment,
      MDR1 disappeared in MCF7/WT but still expressed in MCF7/DOX. (3) There was no
      change in the expression level of BAX, FAS and BRCA2 in both cell lines.
      Conclusively, after validation in clinical samples, overexpression of genes like
      BRCA1, p53, p21, GST, MDR1 and TOPOIIalpha could be used as a prognostic
      biomarker for detection of acquired resistance in breast cancer and as
      therapeutic targets for the improvement of breast cancer treatment strategies.

PMID- 19593674
TI  - The modulation by intensity of the processing of interaural timing cues for
      localizing sounds.
AB  - Features of sounds such as time and intensity are important binaural cues for
      localizing their sources. Interaural time differences (ITDs) and interaural level
      differences are extracted and processed in parallel by separate pathways in the
      brainstem auditory nuclei. ITD cues are small, particularly in small-headed
      animals, and processing of these cues is optimized by both morphological and
      physiological specializations. Moreover, recent observations in mammals and in
      some birds indicate that interaural time and level cues are not processed
      independently but cooperatively to improve the detection of interaural
      differences. This review will specifically summarize what is known about how
      inhibitory circuits improve the measurements of ITD in a sound-level-dependent
      manner.

PMID- 19593675
TI  - Prediction of biliary excretion in rats and humans using molecular weight and
      quantitative structure-pharmacokinetic relationships.
AB  - The aims were (1) to evaluate the molecular weight (MW) dependence of biliary
      excretion and (2) to develop quantitative structure-pharmacokinetic relationships
      (QSPKR) to predict biliary clearance (CL(b)) and percentage of administered dose
      excreted in bile as parent drug (PD(b)) in rats and humans. CL(b) and PD(b) data
      were collected from the literature for rats and humans. Receiver operating
      characteristic curve analysis was utilized to determine whether a MW threshold
      exists for PD(b). Stepwise multiple linear regression (MLR) was used to derive
      QSPKR models. The predictive performance of the models was evaluated by internal
      validation using the leave-one-out method and external test groups. A MW
      threshold of 400 Da was determined for PD(b) for anions in rats, while 475 Da was
      the cutoff for anions in humans. MW thresholds were not present for cations or
      cations/neutral compounds in either rats or humans. The QSPKR model for human
      CL(b) showed a significant correlation (R (2) = 0.819) with good prediction
      performance (Q (2) = 0.722). The model was further assessed using a test group,
      yielding a geometric mean fold-error of 2.68. QSPKR models with significant
      correlation and good predictability were also developed for CL(b) in rats and
      PD(b) data for anions or cation/neutral compounds in rats and humans. Both CL(b)
      and PD(b) data were further evaluated for subsets of MRP2 or P-glycoprotein
      substrates, and significant relationships were derived. QSPKR models were
      successfully developed for biliary excretion of non-congeneric compounds in rats
      and humans, providing a quantitative prediction of biliary clearance of
      compounds.

PMID- 19593676
TI  - Principles of modular tumor therapy.
AB  - Nature is interwoven with communication and is represented and reproduced through
      communication acts. The central question is how may multimodal modularly acting
      and less toxic therapy approaches, defined as modular therapies, induce an
      objective response or even a continuous complete remission, although single
      stimulatory or inhibitingly acting drugs neither exert mono-activity in the
      respective metastatic tumor type nor are they directed to potentially 'tumor
      specific' targets. Modularity in the present context is a formal pragmatic
      communicative systems concept, describing the degree to which systems objects
      (cells, pathways etc.) may be communicatively separated in a virtual continuum,
      and recombined and rededicated to alter validity and denotation of communication
      processes in the tumor. Intentional knowledge, discharging in reductionist
      therapies, disregards the risk-absorbing background knowledge of the tumor's
      living world including the holistic communication processes, which we rely on in
      every therapy. At first, this knowledge constitutes the validity of informative
      intercellular processes, which is the prerequisite for therapeutic success. All
      communication-relevant steps, such as intentions, understandings, and the
      appreciation of messages, may be modulated simultaneously, even with a high grade
      of specificity. Thus, modular therapy approaches including risk-absorbing and
      validity-modifying background knowledge may overcome reductionist idealizations.
      Modular therapies show modular events assembled by the tumor's living world as an
      additional evolution-constituting dimension. This way, modular knowledge may be
      acquired from the environment, either incidentally or constitutionally. The new
      communicatively defined modular coherency of environment, i.e. the tumor
      associated microenvironment, and tumor cells open novel ways for the scientific
      community in 'translational medicine'.

PMID- 19593677
TI  - Bergmann glial S100B activates myo-inositol monophosphatase 1 and Co-localizes to
      purkinje cell vacuoles in SCA1 transgenic mice.
AB  - Spinocerebellar ataxia-1 (SCA1) is a late onset neurodegenerative disease caused
      by the expansion of a polyglutamine repeat within ataxin-1 protein. The toxic
      effects triggered by mutant ataxin-1 result in degeneration of the neurons in
      cerebellum, brain stem and spinocerebellar tracts. The targeted overexpression of
      mutant ataxin-1 in cerebellar Purkinje cells (PCs) of the SCA1 transgenic mice
      results in the formation of cytoplasmic vacuoles in PCs. These vacuoles appear
      early on before the onset of behavioral abnormalities. Interestingly, we found
      that vacoules contain S100B and vimentin proteins, which normally localize to
      neighboring Bergmann glia (BG). Further, immunohistochemical and specialized
      silver stain analysis revealed that vacuolar formation is associated with
      alterations in the morphology of dendritic spines of PCs. To gain insights into
      the mechanisms of vacuolar formation, we investigated if vacuoles in SCA1 PCs
      have an autophagic origin or are a consequence of some other event. We examined
      the expression levels (by Western blotting) of microtubule-associated protein
      light chain 3 (LC3)-I and LC3-II, and the degradation levels of p62 (a LC3
      partner) in the cerebellar fractions prepared from pre-symptomatic SCA1 and age
      matched wild-type mice. No p62 degradation was observed; however, LC3-II/(LC3-I +
      LC3-II) ratios were significantly altered in SCA1 mice indicating changes in the
      autophagic flux. In addition, LC3 localized to PC vacuoles. Further, we observed
      a co-localization of myo-inositol monophosphatase 1 (IMPA1) with S100B in PC
      vacuoles. IMPA1 is present in PC spines and has been implicated in autophagy. In
      vitro studies using purified IMPA1 and S100B demonstrated that S100B interacted
      with and activated IMPA1. Both apo and Ca(2+)-bound S100B were found to activate
      IMPA1, depending on substrate concentration. IMPA1 is regulated by another
      calcium-binding protein calbindin-D28k (CaB), since we reported earlier that the
      CaB levels are reduced in SCA1 PCs, the activation of IMPA1 by S100B may modulate
      CaB-dependent inositol signaling. This may cause BG-PC interface to degenerate
      resulting in vacuolar formation. In sum, these data indicate that vacuoles
      appearing early in SCA1 PCs could be developing through some unknown autophagic
      mechanism.

PMID- 19593678
TI  - Reactive oxygen species mediate compensatory glomerular hypertrophy in rat
      uninephrectomized kidney.
AB  - Hyperfiltration in glomeruli is the most common pathway to progressive renal
      dysfunction. Moreover, reduction of renal mass by unilateral nephrectomy results
      in an immediate increase in glomerular flow to the remnant kidney, followed by
      compensatory glomerular hypertrophy. Reactive oxygen species (ROS) are involved
      in renal hypertrophic responses; however, the role of ROS in compensatory
      glomerular hypertrophy remains unclear. Therefore, this role was investigated in
      the present study. Wistar rats were randomly placed into two groups:
      uninephrectomized rats (Nx) and uninephrectomized rats treated with tempol (Nx +
      TP). The glomerular volume increased in the Nx 1 week after surgery, but was
      significantly suppressed in the Nx + TP. Levels of phospho-Akt and phospho
      ribosomal protein S6, which are critical for cell growth and hypertrophy, were
      markedly increased in the glomeruli of the Nx, while tempol treatment almost
      abolished the activation of these proteins. These results suggest that ROS have
      important roles in compensatory hypertrophy in glomeruli.

PMID- 19593680
TI  - In vivo and in vitro irritation testing of low concentrations of hydrofluoric
      acid.
AB  - OBJECTIVE: Acidic fluorides are proposed for the treatment of dental erosion. The
      aim of this study was to examine the irritation properties of dilute hydrofluoric
      acid (HF) solutions for potential use in the oral cavity. MATERIAL AND METHODS:
      Hen's egg test-chorioallantoic membrane (HET-CAM): The CAM was accessed by
      careful dissection through the egg shell (n=36, 6 eggs/test solution) and exposed
      to 300 ul of the HF solutions (0.05%, 0.10%, 0.20%, and 1.0%) under macroscope
      examination over the course of 5 min. Mean time-to-coagulation and average
      irritation score were recorded based on appearance of hemorrhage, coagulation,
      and lysis of the blood vessels in the membrane. Mouse skin test: 60 male mice
      were randomly divided into 10 groups of 6 animals each (control, 0.05%, 0.10%,
      0.20%, and 1.0% HF), shaved on the back, exposed to test solution, and euthanized
      after 2 h or 24 h. Skin samples were evaluated by light microscopy, scoring
      epithelial leukocyte infiltration, vascular congestion, and edema. RESULTS: HET
      CAM: 0.05% HF was slightly irritant, 0.1% HF moderately irritant, 0.2% and 1% HF
      strongly irritant. 0.1-1% HF solutions were severely irritating on the eye. Mouse
      skin test: HF concentration was significantly correlated with tissue response,
      and 24-h exposure to 1% HF solution showed focal erosion of the epithelium and
      marked localized subepithelial leukocyte infiltration. CONCLUSION: The results of
      the studies suggest that accidental exposure of soft tissues to solutions
      containing more than 0.2% HF may be harmful.

PMID- 19593681
TI  - Complications in retrosigmoid cranial nerve surgery.
AB  - CONCLUSIONS: Although microvascular decompression (MVD), facial nerve splitting
      (FNS) and neurectomy procedures were safe treatments for hemifacial spasm (HFS),
      trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN) in retrosigmoid
      cranial nerve surgery, fatal and severe complications may occur. It is essential
      to pay great attention to the entire procedure to avoid these complications.
      OBJECTIVE: To report the complications of cranial nerve surgery via the
      retrosigmoid approach. PATIENTS AND METHODS: We reviewed 516 cases of cranial
      nerve surgery via the retrosigmoid approach for HFS, TN and GPN. There were 208
      cases of HFS, of which 117 cases underwent FNS alone and 91 cases underwent
      combined MVD and FNS. There were 273 cases of TN treated by MVD and selective
      neurectomy. There were 35 cases of GPN treated by neurectomy. RESULTS: Of the
      cases with complications, two (0.4%) died. Hearing impairment ranging from mild
      to severe occurred in 31 (6.0%) patients; 4 of these (0.8%) presented total
      hearing loss. Postoperative cerebrospinal fluid leakage occurred in 29 (5.6%)
      cases.

PMID- 19593679
TI  - Evaluation of the importance of astrocytes when screening for acute toxicity in
      neuronal cell systems.
AB  - Reliable, high throughput, in vitro preliminary screening batteries have the
      potential to greatly accelerate the rate at which regulatory neurotoxicity data
      is generated. This study evaluated the importance of astrocytes when predicting
      acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N)
      and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems
      derived from the human NT2.D1 cell line, using biochemical endpoints
      (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH
      depletion). Following exposure for 72 h, the known acute human neurotoxicants
      trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable
      of disrupting biochemical processes in all of the cell systems at non-cytotoxic
      concentrations. Astrocytes provide key metabolic and protective support to
      neurons during toxic challenge in vivo and generally the astrocyte containing
      cell systems showed increased tolerance to toxicant insult compared with the
      NT2.N mono-culture in vitro. Whilst there was no consistent relationship between
      MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these
      data did provide preliminary evidence of modulation of the acute neuronal toxic
      response by astrocytes. In conclusion, the suitability of NT2 neurons and
      astrocytes as cell systems for acute toxicity screening deserves further
      investigation.

PMID- 19593683
TI  - Cellular and molecular bases of neuroplasticity: brainstem effects after cochlear
      damage.
AB  - After a cochlear lesion or auditory nerve damage, afferent connections from
      auditory ganglia can be highly altered. This results in a clear reduction of
      auditory input and an alteration of connectivity of terminals on cochlear nuclei
      neurons. Such a process could stimulate the reorganization of the neural circuits
      and neuroplasticity. Cochlea removal has been demonstrated to be a good model in
      which to analyse brainstem neuroplasticity, particularly with regard to the
      cochlear nuclei. After cochlea removal three main periods of degeneration and
      regeneration were observed. Early effects, during the first week post lesion,
      involved acute degeneration with nerve ending oedema and degeneration. During the
      second and, probably, the third post lesion weeks, degeneration was still
      present, even though a limited and diffuse expression of GAP-43 started. Around 1
      month post lesion, degeneration at the cochlear nuclei progressively disappeared
      and a relevant GAP-43 expression was found. We conclude that neuroplasticity
      leads neurons to modify their activity and/or their synaptic tree as a
      consequence of animal adaptation to learning and memory. For the human being
      neuroplasticity is involved in language learning and comprehension, particularly
      the acquisition of a second language. Neuroplasticity is important for
      therapeutic strategies, such as hearing aids and cochlear implants.

PMID- 19593682
TI  - Hair cell progenitors: identification and regulatory genes.
AB  - Hair cell loss in higher vertebrates appears to be permanent. Progenitors that
      are quiescent in the organ of Corti are the best candidates for the restoration
      of the different cell types in the organ of Corti. However, little is known about
      the presence of these progenitors and their capacity to differentiate into hair
      cells. This review will first highlight recent findings concerning the
      identification of progenitor cells that are able to proliferate and to
      differentiate into hair cells. Principal factors impinging on this process are
      then reviewed. Auditory hair cell progenitors have been identified and, under
      appropriate conditions, are capable of proliferating and differentiating into
      hair cells. Characterization of signals that maintain, expand and regulate these
      progenitors will be essential for the biomedical application of stem cell
      populations to restore hearing.

PMID- 19593684
TI  - Cystic neck lesions: clinical, radiological and differential diagnostic
      considerations.
AB  - CONCLUSIONS: Metastatic disease should always be considered as a potential
      differential diagnosis in the adult patient with a cystic neck lesion.
      OBJECTIVES: The most common cause of a cystic neck lesion in young adults is a
      branchial cleft cyst (BCC). In older patients metastatic lymph nodes may be
      easily misdiagnosed as BCC. This study aimed to investigate the incidence of
      unsuspected carcinoma in routinely excised cervical cysts at a tertiary care
      teaching hospital and to determine the characteristics of benign BCC and cystic
      malignancy in preoperative imaging. PATIENTS AND METHODS: A total of 196
      consecutive adult patients operated on with the initial diagnosis of benign
      lateral cervical cyst were identified and the hospital charts and imaging studies
      were reviewed. The mean age of the patients was 40 years (range 17-79 years).
      RESULTS: Metastatic squamous cell carcinoma was demonstrated histologically
      postoperatively in six (3.1%) patients and metastatic papillary thyroid carcinoma
      in one (0.5%) patient. Therefore, the incidence of unsuspected carcinoma in the
      cystic neck lesions initially diagnosed as BCC was 3.6%. The preoperative imaging
      appearances of these lesions had been considered identical to that of BCC.

PMID- 19593686
TI  - Contribution of histological, serological, and genetic factors to the clinical
      heterogeneity of adult-onset coeliac disease.
AB  - OBJECTIVE: Although the factors predisposing to coeliac disease (CD) are largely
      understood, it remains unclear what determines the clinical heterogeneity of the
      disease. The aim of this study was to explore the contribution of histological,
      serological, and genetic factors to disease presentation. MATERIAL AND METHODS:
      The study was designed as a retrospective chart review of 384 unrelated Caucasian
      patients diagnosed with CD after the age of 16 at a single UK centre. RESULTS: We
      found that 8.8% of IgA-competent CD patients were endomysial antibody (EMA)
      negative. Compared with the EMA-positive group, EMA-negative CD patients had a
      lower prevalence of iron deficiency (52.0% versus 72.6%, p=0.03) and Marsh IIIb-c
      lesions (66.7% versus 85.3%, p=0.03). Histological severity at diagnosis
      correlated with anaemia (p<0.01), folate deficiency (p<0.01), and iron deficiency
      (p=0.05), but no other laboratory or clinical features. Compared with human
      leucocyte antigen (HLA)-DQ2.5-positive patients, those carrying HLA-DQ2.2 were
      similar in terms of all the characteristics we considered, whereas those carrying
      HLA-DQ8 had a lower frequency of EMA positivity (62.5% versus 92.6%, p<0.01). The
      proportion of EMA-positive patients increased with frequency of the HLA-DQB1*0201
      allele (76.7% versus 92.3% versus 96.4% for 0 versus 1 versus 2 alleles, p<0.01);
      no other evidence of a gene-dose effect of HLA-DQB1*0201 was observed.
      CONCLUSIONS: Histological severity at diagnosis of CD is associated with anaemia
      and some micronutrient deficiencies, but no other clinical features. The
      proportion of EMA-positive patients is higher amongst those carrying HLA-DQ2 than
      in those carrying HLA-DQ8, and is highest in HLA-DQ2 homozygotes. We found no
      correlation between frequency of the HLA-DQ alleles encoding HLA-DQ2.5 and CD
      severity.

PMID- 19593688
TI  - The impact of body mass index and Helicobacter pylori infection on gastro
      oesophageal reflux symptoms: a population-based study in Northern Norway.
AB  - OBJECTIVE: Increased body mass index (BMI) has been proposed as a risk factor for
      gastro-oesophageal reflux symptoms. The aim of this study was to evaluate the
      effect of BMI and Helicobacter pylori on reflux symptoms in an adult population.
      MATERIAL AND METHODS: For this cross-sectional, population-based study from Bodo
      and Sorreisa communities in Northern Norway, a total of 3927 adults were invited
      to complete a questionnaire on gastrointestinal symptoms and to provide stool
      samples for the assessment of H. pylori. Reflux symptoms were considered present
      when a reflux syndrome score was > or =2 according to the Gastrointestinal
      Symptom Rating Scale (GSRS). RESULTS: The response rate was 44.2%, and 44.7% of
      the respondents were male. Age-adjusted prevalences were: for overweight, 35.6%
      (95% CI (32.4%; 38.8%)); for obesity, 10.0% (8.4%; 11.6%); for H. pylori: 21.2%
      (19.1%; 23.9%) and for reflux symptoms: 21.7% (19.5%; 23.9%). In the logistic
      regression analyses, H. pylori and smoking were not risk factors for reflux
      symptoms, whereas male gender (OR 4.78 (95%CI (1.88; 12.1)), age (1.01 (1.00;
      1.03)) and overweight (1.51 (1.14; 2.00)) were. When stratified by gender,
      overweight and age were independent risk factors for reflux symptoms in females
      only, whereas H. pylori infection was protective against such symptoms in men.
      Models including these parameters could only explain 3% of the variations in
      reflux symptoms. CONCLUSIONS: BMI is an independent risk factor for gastro
      oesophageal reflux symptoms among healthy female adults, but contributes only to
      a minor part of the variation in these symptoms. H. pylori is protective against
      reflux symptoms in men.

PMID- 19593687
TI  - Early detection of recurrence after endoscopic treatment for early gastric
      cancer.
AB  - OBJECTIVE: Although there have been many reports regarding clinical outcomes of
      endoscopic treatment for early gastric cancer (EGC), little is known about
      detection of recurrence after endoscopic submucosal dissection (ESD). This study
      aims to clarify the clinical value of serological marker or imaging tools,
      including conventional CT and PET-CT scans, in detecting recurrent gastric cancer
      after ESD in Korea. MATERIAL AND METHODS: From July 2004 to March 2008, 212
      patients who had received ESD for EGC were enrolled in the study. For
      preoperative staging, conventional CT and PET-CT scans were performed in 141
      patients, and for detection of recurrence of cancer, conventional CT, PET-CT
      scans and tumour marker; CEA, CA19-9, AFP were checked in 165 patients. RESULTS:
      The local recurrence rate was 4.7% (10/212) during the study period. At 9 months
      after endoscopic treatment, 3 cases recurred. Four showed recurrence at 12
      months, 2 at 18 months and 1 at 24 months. The positive rate was 7.1% (10/141) in
      conventional CT and 0% (0/24) in PET-CT scans for preoperative staging.
      Conventional CT and PET-CT scans could not detect local recurrence of cancer
      during the follow-up period. Tumour markers did not show any significant
      correlation with recurrence of cancer. CONCLUSIONS: The study suggests that
      conventional CT, PET-CT scans and tumour marker have no role in the primary
      surveillance of early gastric cancer and/or in detecting recurrence after
      endoscopic treatment. For early diagnosis of recurrence after endoscopic
      treatment, a biopsy specimen from the endoscopic examination has to be obtained
      at regular intervals.

PMID- 19593689
TI  - Peginterferon plus ribavirin over two years may be successful in patients with
      chronic hepatitis C and a very slow virologic response.

PMID- 19593690
TI  - Relative role of APC and MUTYH mutations in the pathogenesis of familial
      adenomatous polyposis.
AB  - OBJECTIVE: Familial adenomatous polyposis (FAP) is an interesting model for the
      study of colorectal tumour. Two genes contribute to the FAP phenotype - APC and
      MUTYH - but their relative role is still undefined. The objective of this study
      was to evaluate the contribution of the two genes to the pathogenesis of FAP by
      means of a series of FAP families. MATERIAL AND METHODS: Sixty-one unrelated
      families with a diagnosis of FAP and a total of 187 affected individuals were
      evaluated. After extracting DNA, APC and MUTYH genes were sequenced. RESULTS: In
      the whole series of patients, colectomy with ileorectal anastomosis was the most
      frequent surgery, although the number of patients treated by total
      proctocolectomy and ileoanal anastomosis was increasing. Duodenal and jejunal
      ileal adenomas were present in more than half of the patients. Constitutional
      mutations were detected in 37 of the 45 families (82.2%); there were 33 families
      with APC and 4 with MUTYH alterations. Age at onset of polyposis and age at
      surgery were 10-15 years delayed for carriers of MUTYH mutations; cancer at
      diagnosis was frequent, and extracolonic manifestations were diagnosed in the
      majority of MUTYH-positive families. MUTYH-associated polyposis showed the
      horizontal transmission expected for recessive inheritance (at variance with the
      dominant pattern seen with APC mutations). CONCLUSIONS: At least two genes are
      associated with the FAP phenotype. APC mutations account for the majority of
      cases, while MUTYH mutations can be observed in 10% of patients. There are few
      but definite differences between APC- and MUTYH-associated FAP, such as age at
      diagnosis and pattern of transmission.

PMID- 19593691
TI  - Holiday souvenirs from the Mediterranean: three instructive cases of visceral
      leishmaniasis.
AB  - With expanding travel activities, visceral leishmaniasis increasingly occurs in
      non-endemic areas and affects immunocompetent individuals with no other risk
      factor than holidays at the Mediterranean coast. We report 3 instructive Swiss
      cases of visceral leishmaniasis presenting with fever of unknown origin and
      pancytopenia and review current diagnostic and therapeutic concepts.

PMID- 19593694
TI  - Human growth from the cell to the organism: saltations and integrative
      physiology.
AB  - The Society for the Study of Human Biology has been at the forefront in the
      scientific study of human growth. The documentation of variability in growth
      rate, size, and tempo across populations has provoked exploration for sources of
      this diversity, and the mechanisms by which environmental and genetic factors
      influence phenotypic expressions of growth biology. At a time when adult health
      and well-being are posited to reflect early development, the details of early
      growth patterns are increasingly sought as explanatory domains underlying
      lifespan health. A review of recent observations detailing events that occur in
      growth and differentiation during embryological and fetal development is
      considered for insights into mechanisms that may be operative in a putative
      cascade of growth biology operating across developmental ages. Cellular growth
      and differentiation are posited to be a process of integrative physiology, with
      increasing complexity in organismic growth achieved through modularity and
      temporally-differentiated signals. The flexible patterns of human growth are
      hypothesized to reflect the variability in timing and amount of growth
      saltations, which are the outcome of cross-talking signaling systems in an
      energy/immune integrating complex. This is an adaptive system, flexible and
      responsive to the challenges of developmental biology in changing environments.

PMID- 19593695
TI  - The recognition and treatment of growth disorders - a 50-year retrospective.
AB  - The past 50 years have seen great progress in the understanding and treatment of
      classic growth disorders. Advances such as the recognition of hormone receptor
      defects, the development of recombinant growth hormone, and the expanding
      awareness of epigenetic phenomena affecting growth are among these great
      achievements. Yet growth failure remains a pervasive problem among children with
      complex health conditions, such as survivors of childhood cancers, premature
      infants, organ transplant recipients, and children with cystic fibrosis. The
      significant increases in life expectancy among these groups underscores the
      potential consequences of poor growth, whether due to the underlying conditions
      or medical treatments, as they may have long-lasting effects into adulthood. The
      ongoing contributions of human biologists to the study of human growth remain
      essential in the recognition and treatment of growth disorders, by defining
      normal patterns of growth and body composition, the interplay of growth and
      maturation, the role of environmental, behavioral and genetic factors, and the
      long-term consequences of growth patterns. Examples will be given based on two
      common genetic disorders, cystic fibrosis and sickle-cell anemia, to highlight
      the relationships between growth failure, survival, and malnutrition. Also, a
      study of bone mineral accretion in children with cystic fibrosis will illustrate
      the importance of understanding patterns of growth in healthy children, and their
      application in the diagnosis and management of children with chronic disease.
      These examples accentuate the need for continued participation of human
      biologists in the study of growth and development and the care of children.

PMID- 19593696
TI  - Independent and combined influence of AGTR1 variants and aerobic exercise on
      oxidative stress in hypertensives.
AB  - Abstract Angiotensin II (AngII), via the AngII type 1 receptor (AT(1)R),
      contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the
      risk of cardiovascular (CV) disease, presumably by reducing the grade of
      oxidative stress. We investigated the independent and combined influence of the
      AGTR1 A1166C and -825 T/A polymorphisms on oxidative stress and plasma AngII
      responses to AEXT in pre- and stage 1 hypertensives. Urinary 8-iso-PGF(2alpha)
      significantly increased with AEXT (p=0.002); however, there were no significant
      changes in superoxide dismutase activity or AngII levels. There was a significant
      difference in the change in AngII levels with AEXT between A1166C genotype groups
      (p=0.04) resulting in a significant interactive effect of the A1166C polymorphism
      and AEXT on the change in AngII (p<0.05). Only the TT genotype group of the -825
      T/A polymorphism had a significant reduction in plasma AngII (p=0.02). Risk
      allele analysis revealed a significant reduction in plasma AngII (p=0.04) and a
      significant increase in urinary 8-iso-PGF(2alpha) (p=0.01) with AEXT in
      individuals with two risk alleles only. Our findings suggest that variation in
      the AGTR1 gene is associated with differential changes in plasma AngII but not
      oxidative stress.

PMID- 19593697
TI  - Proangiogenic cytokines produced by non-Hodgkin lymphoma tumor cells induce
      angiogenesis in infiltrated bone marrow samples.

PMID- 19593699
TI  - Guiding change: provider voices in youth pre-abortion counselling in urban
      Vietnam.
AB  - Pre-abortion counselling has a role in promoting safe sex practices and in
      preventing repeated unplanned pregnancies and repeated abortions among abortion
      seeking women. Such counselling is essential in Vietnam, especially given the
      common use of abortion. Arguably, in Ho Chi Minh City, Vietnam, the delivery of
      pre-abortion counselling is more urgent for young women, who have historically
      been ignored by State reproductive health initiatives and are increasingly
      exposed to transmission of sexually transmitted infections (STIs), unplanned
      pregnancies and abortion. This paper charts urban Vietnamese service providers'
      discourses in pre-abortion counselling specific for reducing risks of additional
      unwanted pregnancies, repeat abortion and STI/HIV transmission among young
      Vietnamese women. Thirteen providers working in counselling delivery, management
      and programme-planning at the Reproductive Health Care Centre of Ho Chi Minh City
      participated in this study. Through qualitative interviews, this paper elicits a
      range of provider attitudes, considerations and approaches in pre-abortion
      counselling and presents these discourses using participant anecdotes.
      Demonstrated among participant responses were five key pre-abortion counselling
      phases for promoting effective family planning among young women. Topics covered
      in these counselling phases included abortion complications, post-abortion
      fertility return, contraception, behaviour change and STI/HIV prevention and
      sexual and reproductive health basics (SRH). The service provider discourses
      gleaned from this study are foundational for further research and development of
      best practice guidelines in pre-abortion counselling.

PMID- 19593698
TI  - Cell-specific temporal infection of the brain in a simian immunodeficiency virus
      model of human immunodeficiency virus encephalitis.
AB  - Increasing evidence supports early brain infection by human immunodeficiency
      virus (HIV). Definitive temporal studies determining when and within which brain
      cells viral DNA is present are lacking. This study utilized simian
      immunodeficiency virus (SIV)-infected macaques sacrificed at days 10, 21, 56, and
      84 post inoculation. Laser-microdissection isolated pure perivascular macrophage,
      parenchymal microglia, and astrocyte populations. Nested polymerase chain
      reaction (PCR) and sequencing determined the presence and characteristics of SIV
      V3 and V1 env DNA from each population. At day 10, SIV DNA was detected in
      perivascular macrophage and astrocytes but not parenchymal microglia. gp41
      expression was restricted to perivascular macrophage. At day 21, SIV DNA was not
      detected in any cell type. At day 56, SIV DNA was detectable in perivascular
      macrophage from one of two macaques, with no gp41 expression detected. At day 84
      (morphologic and clinical encephalitis), SIV DNA was detected in all cell types,
      gp41 was only detected in perivascular macrophage and parenchymal microglia. The
      neurovirulent molecular clone, SIV/17E-Fr, was the only genotype identified in
      the brain cell populations. Early, productive brain SIV infection was transient
      and restricted to trafficking perivascular macrophage. During the nonencephalitic
      stage, there was a period of time when no SIV DNA could be detected in the brain
      cell populations. SIV was then seen to reenter the brain via infected
      perivascular macrophage, leading to productive infection of brain parenchymal
      macrophage/microglia with a terminal phase of encephalitis. These data challenge
      current notions of a HIV reservoir within latently infected, semipermanent brain
      cells and has significant implications for the timing and design of therapies to
      prevent HIV encephalitis (HIVE).

PMID- 19593700
TI  - Sense of coherence in Crete and Sweden: key findings and messages from a
      comparative study.
AB  - BACKGROUND/OBJECTIVE: The concept of ''sense of coherence'' (SOC) was introduced
      in 1987 by Aaron Antonovsky to describe a dispositional orientation, ''a way of
      seeing the world'', which is presumed to enhance health. This study reports on
      the results of the first implementation of SOC in rural Crete and discusses the
      findings, with a view to the potential impact on primary care delivery in rural
      Crete. METHODS: This study forms part of a follow-up project initially
      established in 1988 in the rural area of Spili, Crete. All participants of the
      initial study still living in the area (n = 248) were eligible. Data were
      obtained from 200 subjects (91 males and 109 females) aged 28-92 years, resulting
      in a second-phase participation rate of 80.7%. The SOC scales (both the SOC-29
      and SOC-13 forms) were recorded for 175 (87.1%) of the participants. RESULTS:
      Comparing the SOC scores among Cretan males and females, there is a statistically
      significant difference (p < 0.0001), with men reporting a higher sense of
      coherence than women, regardless of the form of the questionnaire used. Cretan
      women seem to score significantly lower than their Swedish counterparts (p <
      0.0001), while Cretan men tend to report a higher SOC compared to their matched
      Swedish reference population (p = 0.07). DISCUSSION: The study introduces other
      issues worthy of additional research, particularly with regard to the
      significantly lower SOC scores obtained by Cretan women, compared to Cretan men.
      These low SOC scores raise the issue of a potential increase of psychiatric
      morbidity in the area, leading to a high impact on primary care services. Future
      investigation into the health impact of SOC factors could be of value to primary
      care physicians located in rural Crete.

PMID- 19593701
TI  - A small mouse-click for a doctor, a giant leap in healthcare.

PMID- 19593702
TI  - Long-term left ventricle assist device (LVAD) therapy with rotary pumps.

PMID- 19593703
TI  - Targeting CD24 for treatment of ovarian cancer by short hairpin RNA.
AB  - BACKGROUND AIMS: CD24 is markedly overexpressed in ovarian cancer and plays a
      critical role in ovarian cancer survival and metastasis, rendering it an
      interesting target for anti-tumor therapy. Using short hairpin RNA (shRNA)
      targeting CD24, we aimed to investigate the anti-tumor efficacy of CD24 knockdown
      in ovarian cancer cells in vitro and in vivo. METHODS: CD24 shRNA vector (CD24
      shRNA) and empty plasmid vector (EP) were transfected into ovarian cancer SKOV3
      cells and the knockdown efficacy assessed by Western blot analysis. The effects
      of CD24 knockdown in SKOV3 cells in vitro, including cell viability and
      apoptosis, were determined using methyl thiazolyl blue tetrazolium bromide (MTT),
      flow cytometry and propidium iodide (PI) staining assays. The effects in vivo of
      CD24 knockdown on angiogenesis, cell proliferation and apoptosis were assessed
      using immunohistochemistry against CD31, proliferating cell nuclear antigen
      (PCNA) and terminal deoxynucleotidyl transferase-mediated nick end-labeling
      (TUNEL) assays. RESULTS: Transfection of CD24-shRNA effectively down-regulated
      CD24 expression in vitro and in vivo. Administration of CD24-shRNA into nude mice
      bearing ovarian cancer significantly suppressed tumor volume growth. CONCLUSIONS:
      Knockdown of CD24 expression by CD24-shRNA significantly inhibited cell viability
      and induced apoptosis of SKOV3 cells in vitro. Administration with CD24-shRNA in
      vivo suppressed tumor volume increase by microvessel density (MVD) decrease, cell
      proliferation inhibition and apoptosis induction. All the data suggested that
      knockdown of CD24 by shRNA might be a potential therapeutic approach against
      human ovarian cancer.

PMID- 19593704
TI  - Concise preparation of biologically active chitooligosaccharides.
AB  - Chitooligosaccharides (COSs) have demonstrated a diverse array of biological
      activities. Here we report a concise preparation method for tetra-N-acetyl
      chitotetraose and penta-N-acetyl-chitopentaose. The FACE analysis showed that the
      partially N-acetylated COS mixture mainly contained glucosamine (GlcN) and some
      oligomers [(GlcN)(n), n = 2-7]. The N-acetyl-D-glucosamine (GlcNAc) and
      peracetylated COSs [(GlcNAc)(n), n = 2-7] were synthesised by treating the
      partially N-acetylated COS mixture with Ac(2)O-NaOAc. The peracetylated
      chitotetraose and chitopentaose were obtained by isolation of peracetylated COS
      mixture. NaOMe in dry MeOH was used for the deacetylation of peracetylated
      chitotetraose and chitopentaose, to give the tetra-N-acetyl-chitotetraose and
      penta-N-acetyl-chitopentaose, respectively.

PMID- 19593705
TI  - Commentary: evaluation of driver fitness--the role of continuing medical
      education.
AB  - Faced with demographic trends that predicted large increases of older drivers
      within a relatively short period combined with the realization that screening for
      driver fitness was largely dependent upon health professionals, principally
      physicians, in 2004 the Societe de l'assurance automobile du Quebec (SAAQ)
      initiated measures that sought to achieve better cooperation with the health
      professionals performing the screening. A program was initiated that sought to
      improve the health professionals' understanding of road safety considerations.
      This article examines the measures included in this program and their results.
      SAAQ statistics show the benefit of the SAAQ's continuing medical education (CME)
      program. Since the initiation of the program the number of reports submitted by
      physicians has increased exponentially, whereas police reports have remained
      constant. Informed physicians report drivers with medical problems that may
      affect driver fitness when they are aware that the licensing agency's decisions
      are based principally upon valid functional evaluations. Discretionary reporting
      may be as effective as mandatory reporting when physicians are knowledgeable
      about the road safety implications of medical conditions.

PMID- 19593706
TI  - A comparison of drivers with high versus low perceived risk of being caught and
      arrested for driving under the influence of alcohol.
AB  - OBJECTIVES: To examine the beliefs, behaviors, and knowledge of drivers
      concerning drunk driving and to compare those with greater or lesser perceptions
      of risk of being caught driving while impaired. METHODS: A random-digit-dial
      telephone survey was conducted of 850 licensed drivers throughout Maryland who
      reported their driving behaviors, crash history, beliefs about various alcohol
      countermeasures, and their knowledge of state alcohol laws. RESULTS: Most drivers
      (72%) did not feel that it was very likely that they would be stopped by the
      police if they drove after having too much to drink (low-risk perceivers). High
      risk perceivers (28%) felt that it was very likely that they would be stopped and
      most (70%) felt that it was very likely that they would be arrested and
      convicted. Less than half (45%) of the low-risk perceivers felt that they would
      be arrested and convicted if they drove impaired. High-risk perceivers were
      significantly more likely to be non-white, less likely to drive 10 mph above the
      speed limit, but were more likely have five or more tickets in their lifetime and
      believed that sobriety checkpoints are effective. They were also more aware of
      laws regarding mandatory use of ignition interlocks for repeat driving under the
      influence (DUI) offenders and the zero tolerance law for under-21-year-old
      drivers. CONCLUSION: There is a need to elevate the perceived risk of being
      caught when driving while alcohol impaired. Despite several years of prevention
      programs, a substantial portion of Maryland drivers do not feel it very likely
      that they would be stopped by the police if they were to drive after drinking too
      much. Drivers who perceive these risks are more accepting of enforcement and
      treatment countermeasures and are more likely to report safer driving behaviors.

PMID- 19593707
TI  - Does knowledge of teen driving risks and awareness of current law translate into
      support for stronger GDL provisions? Lessons learned from one state.
AB  - OBJECTIVE: Many states are considering strengthening their graduated driving
      licensing (GDL) systems for teenage drivers but most do not know the level of
      public support for proposed upgrades. This study provides a method for states to
      identify specific demographic groups that may differ with regard to their
      awareness of teen driving risks, knowledge of current GDL law, and support for
      GDL upgrades. METHODS: A 28-item questionnaire was administered to Connecticut
      adults by phone survey during January 2008. We collected demographic information
      and whether respondents understood driving risks, were aware of the current GDL
      system, and whether they would support GDL upgrades. The state's motor vehicle
      crash file (1999-2006) was used to calculate motor vehicle crash rate among 16-
      and 17-year-old drivers by town and correlate that with support for GDL upgrades.
      RESULTS: Eight hundred seven people were interviewed. More women than men (92%
      vs. 86%, p < .05) and more parents than other adults (96% vs. 84%, p < .01) were
      aware of the current learner's permit law. Female respondents (55% vs. 43%, p <
      .01) and adults who were not parents (54% vs. 45%, p < .05) were more likely to
      support increasing the minimum driving age. Parents were more aware than other
      adults (91% vs. 73%, p < .01) of the supervised driving provision. Women were
      more supportive of a supervised driving upgrade (83% vs. 69, p < .01). There was
      more support for a night restriction upgrade among other adults than parents (59%
      vs. 51%, p < .05), and the lowest support was in affluent towns (38%). Two thirds
      supported a passenger restriction upgrade with no differences based upon sex or
      geographic location. There was less support for an increased penalties in
      Fairfield County when compared to all other counties (55% vs. 63%, p < .05) and
      more support in Hartford County versus all other counties (70% vs. 58%, p < .05).
      CONCLUSIONS: Parents of Connecticut teens were more knowledgeable of current law
      but less supportive of GDL upgrades compared to other adults. Women were more apt
      to favor GDL upgrades than men. This study identifies subgroups that can be
      targeted for prevention activities and illustrates a useful method to assess
      public support for GDL upgrades.

PMID- 19593708
TI  - Opium consumption and the risk of traffic injuries in regular users: a case
      crossover study in an emergency department.
AB  - OBJECTIVE: The cause-specific annual death rate due to traffic injuries is around
      30 in 100,000 in Iran. On the other hand, this country has the highest proportion
      of opiate users in the world. Little is known about the transient effect of opium
      on traffic injuries. The objective of this study was to explore the effect of
      opium consumption on traffic injuries in drivers who use opium. METHODS: Seventy
      five regular opium users who suffered traffic injuries were studied in a case
      crossover investigation. The study subjects had been admitted to the single
      trauma emergency department in Kerman, a city in southeast Iran. The relative
      risk (RR) of short-term opium effect was estimated by considering frequency of
      driving after opium consumption during 6 hours before the accident in comparison
      to the usual frequency of driving after opium consumption by the same persons.
      Stratified data analysis was performed by the Mantel-Haenszel method. RESULTS:
      The opium consumption of drivers up to 6 hours before the accident was associated
      with an increased RR = 3.2, 95 percent confidence interval (CI): 1.9, 5.4. The
      third hour after consumption had the greatest magnitude of effect considering RR
      = 4.29, 95 percent CI:2.65, 6.95. CONCLUSIONS: These results suggest a heightened
      risk of traffic injuries after opium consumption in regular users. The RR in the
      third hour after consumption could be explained by considering the greater
      probability of driving compared to the immediate hours after use, rather than
      peak effect time of opiates. The results indicate necessity of regular assessment
      of all common drivers, especially truck and bus drivers, regarding use of opium.

PMID- 19593709
TI  - Effectiveness of media and enforcement campaigns in increasing seat belt usage
      rates in a state with a secondary seat belt law.
AB  - OBJECTIVE: In 2005, in terms of seat belt usage rates, Nevada ranked third
      nationally and first among states with secondary seat belt use enforcement laws
      in the United States. An effective combination of a media-based education and
      enforcement campaign helped in this regard. The objective of this article is to
      document the effectiveness of enforcement and media-based education and outreach
      campaigns on the seat belt usage rates in Nevada, a state with a secondary seat
      belt usage law. METHODS: Observational data on seat belt usage and passenger
      fatality data are used to evaluate the effectiveness of enforcement campaigns and
      media-based education and outreach campaigns. Data based on observations of about
      40,000 vehicles in each of the years 2003 to 2005 were analyzed. RESULTS:
      Statistical analyses show that a significant increase in seat belt usage rates
      among both drivers and passengers for both genders resulted from the accompanying
      the media and enforcement campaigns. CONCLUSIONS: The results from this study
      indicate that effective and well-planned media/enforcement campaigns can have a
      significant impact on seat belt usage rates even in a state where the enforcement
      of seat belt laws can only be as a secondary violation. They validate and expand
      on findings from other efforts documented in the literature. These results
      demonstrate that, if coordinated properly, media and enforcement campaigns work
      very effectively in increasing seat belt usage rates even in states with
      secondary seat belt laws.

PMID- 19593711
TI  - During which month is it riskiest to drive in the United States?
AB  - OBJECTIVES: This study examined the variation in the U.S. road fatality rate per
      distance driven across the months of the year. METHOD: The monthly fatality rates
      were analyzed for a 13-year period from 1994 through 2006. RESULTS: The results
      indicate a systematic seasonal variation in the road fatality rate, with the
      highest rate in October and the lowest rate in March. CONCLUSION: The obtained
      seasonal variation in the road fatality rate is likely a result of a joint
      influence of several factors that exhibit seasonal variations themselves (the
      duration of darkness, consumption of alcohol, proportion of older drivers, amount
      of leisure driving, and inclement weather).

PMID- 19593710
TI  - Could ESC (Electronic Stability Control) change the way we drive?
AB  - OBJECTIVE: ESC (Electronic Stability Control) is a crash avoidance technology
      that reduces the likelihood of collisions involving loss of control. Although
      past and emerging research indicates that ESC is effective in reducing collision
      rates and saving lives, and its inclusion in all vehicle platforms is encouraged,
      drivers may demonstrate behavioral adaptation or an overreliance on ESC that
      could offset or reduce its overall effectiveness. The main objective of the
      present study was to determine whether behavioral adaptation to ESC is likely to
      occur upon the widespread introduction of ESC into the Canadian vehicle fleet.
      Secondary objectives were to confirm the results of a previous ESC public survey
      and to generate a baseline measure for the future assessment of planned and
      ongoing ESC promotional activities in Canada. METHODS: Two separate telephone
      surveys evaluated drivers' perceptions and awareness of ESC. The first surveyed
      500 randomly selected owners/drivers of passenger vehicles. The second surveyed
      1017 owners/drivers of 2006-2008 ESC-equipped passenger vehicles from the
      provinces of Quebec and British Columbia, Canada. RESULTS: Though ESC drivers
      were much more likely than drivers of other vehicles to be aware of ESC (77% vs.
      39%) and that their own vehicle was equipped with it (63% vs. 8%), 23 percent had
      never heard of it. Ninety percent of drivers who knew that their vehicle was
      equipped with ESC believed that ESC had made it safer to drive and reported being
      confident that ESC would work in an emergency. Twenty-three percent of ESC owners
      who knew their vehicle had ESC reported noticing long-lasting changes in their
      driving behavior since they began driving the vehicle. CONCLUSIONS: Collectively,
      results suggest that behavioral adaptation to ESC is likely in certain drivers;
      however, its proven effectiveness in reducing the likelihood of being involved in
      a serious crash probably outweighs any potential increases in unsafe driving. To
      fully benefit from ESC, vehicle manufacturers are encouraged to market ESC
      equipped vehicles in a realistic, safe manner. Driver training and safety
      organizations are also encouraged to provide balanced educational information
      about ESC to their members.

PMID- 19593712
TI  - Back-over collisions in child pedestrians from the Canadian Hospitals Injury
      Reporting and Prevention Program.
AB  - OBJECTIVE: The objective of the current study was to describe the burden of back
      over collisions within the context of other child pedestrian collisions as
      identified through a pediatric emergency room injury surveillance database.
      METHODS: Injury data for child pedestrian motor vehicle collisions from 1994 to
      2003 were obtained from the Canadian Hospitals Injury Reporting and Prevention
      Program (CHIRPP). Back-over collisions involving children under the age of 14
      were identified and classified by written narratives. Characteristics of children
      involved in back-over collisions were described, and for those admitted to
      hospital, the nature of injury was compared with other types of child pedestrian
      collisions. RESULTS: There were 4295 child pedestrian motor vehicle collisions
      reported to CHIRPP during the study time period. Of the 4295 children, 148 (3.4%)
      were injured in a back-over collision, with 49 (33.1%) of these collisions
      involving a vehicle backing out of a driveway. Children involved in back-over
      collisions were significantly younger than those in forward-moving/other
      collisions; however, almost 50 percent of back-over collisions involved children
      older than age 4. Children involved in back-over collisions on driveways were
      significantly younger than those involved in collisions occurring at other
      locations. Of those admitted to hospital, children in back-over collisions were
      more likely to sustain injuries to internal organs. Children in back-over
      collisions were less likely to sustain severe/mild head injuries and hip/leg
      fractures. CONCLUSIONS: Although back-over collisions represent a small
      proportion of pedestrian motor vehicle collisions, they tend to involve more
      severe injuries, as indicated by their admission to hospital. It was found that
      older children are also at risk of back-over collisions and back-over collisions
      occur in areas other than driveways. In order to lessen the burden of back-over
      collisions, interventions must address children of different ages and a variety
      of locations.

PMID- 19593713
TI  - Warning drivers about potential congestion as a means to reduce frustration
      driven aggressive driving.
AB  - OBJECTIVE: This research was conducted to examine the consequences of forewarning
      drivers about impending congestion on aggressive driving behavior. Some have
      argued that aggressive driving stems from frustration experienced on the roadway
      (often due to congestion), and that by warning drivers about congestion,
      frustration, and consequently aggressive driving, can be reduced. METHODS: The
      study employed an experimental design, where participants (whose dispositional
      driver anger was measured using the Driver Anger Scale) were instructed to
      operate an instrumented vehicle along a prescribed route containing construction.
      Participants were randomly assigned either to receive a warning about the
      construction or to receive no warning about the congestion. Measures of
      aggressive driving behavior were extracted from video (shot from a camera hidden
      behind the vehicle's license plate) and from an ongoing accelerometer. RESULTS: A
      total of 49 participants completed the study. Analyses of combined measure of
      aggressive driving behavior data revealed a statistically significant main effect
      for dispositional driver anger (with participants scoring higher on the scale
      actually driving more aggressively), as well as interactions between driver anger
      and forewarning. Accordingly, forewarning about potential congestion reduced
      aggressive driving behavior for participants high in dispositional anger but
      increased aggressive behavior for participants who were low on dispositional
      anger. CONCLUSION: Some of the results-particularly the increase in aggressive
      driving among participants low in dispositional driver anger who were warning
      about congestion-were unexpected. The interaction effect suggests that the
      strategy providing warnings about upcoming congestion will not necessarily reduce
      frustration among all drivers.

PMID- 19593715
TI  - The relationship between regional economic conditions and the severity of traffic
      crashes.
AB  - OBJECTIVES: To evaluate the relationship between regional economic conditions and
      the severity of injury suffered by victims of traffic crashes. This analysis
      augments the research on the relationship between economic conditions and traffic
      safety by focusing on injury severity per victim, which isolates the protective
      effect to individuals from other traffic safety effects such as crashes per mile
      and aggregate exposure to crashes. METHODS: A crash-specific data set from the
      State of Ohio is used together with county-level economic and demographic data to
      generate estimates that measure the impact of county-level per capita income and
      unemployment rate on the severity of injury suffered by each individual who is
      involved in a crash. The estimates are derived from an ordered probit model that
      controls for other factors that influence injury severity independently of
      economic conditions. RESULTS: The resulting estimates indicate that on average,
      individuals involved in crashes that occur in relatively prosperous counties
      suffer less severe injuries than those in less prosperous counties, holding other
      influential factors constant. Regional per capita income has a proportionally
      greater impact on injury severity than does regional unemployment rate.
      CONCLUSIONS: The estimates indicate that regional economic conditions have a
      statistically significant beneficial impact on traffic safety by improving the
      level of injury suffered by crash victims. Therefore, state and federal public
      policy makers should consider this factor when allocating traffic safety-related
      resources among geographical regions.

PMID- 19593714
TI  - The association of driver age with traffic injury severity in Wisconsin.
AB  - OBJECTIVES: To quantify the association of driver's age with the risk of being
      injured, dying, and experiencing injuries of different severity when involved in
      a motor vehicle crash. METHODS: Data from the Wisconsin Crash Outcome Data
      Evaluation System (CODES) from 2002 to 2004 were used to study 602,964 drivers of
      a car or truck who were involved in a motor vehicle crash. Odds ratios (OR) or
      relative risk ratios (RRR) and their 95 percent confidence intervals (CIs) were
      calculated for age groups, in relation to the outcomes of injury, fatality, and
      injury severity using logistic regression models, which controlled for sex,
      alcohol use, urban/rural location, seat belt use, ejection, airbag deployment,
      vehicle type, and highway class. RESULTS: Increasing age was strongly associated
      the risk of dying or experiencing severe injuries for drivers involved in motor
      vehicle crashes with the greatest risk in drivers 85 years and older. Compared to
      drivers aged 25-44, drivers 85 years and older had the highest risks for moderate
      injury (ISS = 9-15; RRR = 5.44, 95% CI: 3.97-7.47), severe injury (ISS = 16-74;
      (RRR = 4.32, 95% CI: 2.73-6.84), and fatality (OR = 10.93, 95% CI: 7.76-15.38).
      In contrast, drivers 85 years and older had no increase in risk for minor injury
      (ISS = 1-8; OR = 0.94, 95% CI: 0.84-1.05). CONCLUSIONS: The oldest drivers
      involved in motor vehicle crashes had the highest risk for severe injury and
      fatality. In light of the increasing number of the oldest drivers and their poor
      outcomes from severe trauma, substantial morbidity can be expected to occur in
      the oldest drivers. Evidence-based measures to reduce the risks to older drivers
      should continue to be developed, evaluated, and implemented.

PMID- 19593716
TI  - Road traffic injuries in Iran: the role of interventions implemented by traffic
      police.
AB  - INTRODUCTION: In Iran there are about 70 deaths per day from road traffic
      injuries (RTIs). Despite some interventions having been implemented during the
      past 5 years, the impacts of these interventions on mortality and morbidity rates
      have not been well evaluated. OBJECTIVE: To ascertain and describe the
      epidemiological pattern of RTIs in Iran for the years 2004 to 2007 and to compare
      the epidemiological trends of RTIs, before and 2 years after four road safety
      programs were put into place. METHODS: A 4-year database from two sources, the
      traffic police and medico-legal data, was employed. The morbidity and death rates
      per 10,000 vehicles and per 100,000 populations were calculated as were the odds
      ratios (ORs) for before and after these national interventional programs. The
      four interventions concurrently/simultaneously put into place in 2005 were (1)
      enforcement of laws on the mandatory fastening of seat belts, (2) enforcement of
      the laws on use of motorcycle helmets, (3) enforcement of general traffic laws,
      and (4) mass media educational campaigns on national radio and television.
      FINDINGS: There was a significant decrease in RTI-related death and morbidity
      rates in Iran, after the intervention programs were conducted (P < 0.001). The
      death rate decreased from 38.2 per 100,000 in 2004 to 31.8 in 2007 (OR = 0.83,
      95% CI = 0.82-0.85). The death rate per 10,000 vehicles also showed a significant
      decline from 24.2 to 13.4 (OR = 0.56, 95% CI = 0.55-0.57). Similar reductions
      were seen among nonfatal RTIs. CONCLUSION: These findings demonstrate the role of
      traffic police interventions, initiated simultaneously on a national level, in
      RTI prevention. Though these reductions may not be solely attributable to the
      interventions implemented, they do highlight the importance of the contribution
      made by law enforcement and mass education campaigns.

PMID- 19593717
TI  - Comparison of driving errors between on-the-road and simulated driving
      assessment: a validation study.
AB  - OBJECTIVE: Driving simulation provides a convenient and safe method for assessing
      driving behaviors. Many authors, however, agree that validation is a key
      component of any study that utilizes simulators to assess driving performance.
      The purpose of this study was to test driver response validity by discerning
      whether behavioral responses of drivers, as expressed by type and number of
      errors, are similar on the road and in the simulator. METHODS: We replicated real
      world intersections in our driving simulator (STISIM M500W; Systems Technology
      Inc.) and assessed the number and type of driving errors committed by the same 39
      participants while negotiating a right and a left turn both on the road and in
      the simulator. RESULTS: We found no significant interactions between the type of
      vehicle (road vs. simulator) and the type of turn (right versus left) for any of
      the driving errors, indicating that the same trends exist between driving errors
      made on the road and in the simulator and thus suggesting relative validity of
      the simulator. We also found no significant differences between the road and the
      simulator for lane maintenance, adjustment to stimuli, and visual scanning
      errors, indicating absolute validity for these types of errors. CONCLUSIONS: The
      findings suggest early support for external validity for our driving simulator,
      indicating that the results of assessing driving errors when negotiating turns in
      the simulator can be generalized or transferred to the road under the same
      testing conditions. A follow-up study with larger sample size is needed to
      establish whether driving performance in the simulator is predictive of driving
      performance on the road.

PMID- 19593718
TI  - A new approach to multibody model development: pedestrian lower extremity.
AB  - OBJECTIVE: The goal of this study was to develop a mathematical model of the 50th
      percentile male lower extremity capable of predicting injury risk and simulating
      the kinetic and kinematic response of the pedestrian lower extremity under
      vehicle impact loading. METHODS: The hip-to-foot multibody model was developed
      for the MADYMO software platform using exterior and interior geometry and
      inertial properties from a detailed finite element model (FEM) of the human lower
      extremity and stiffness and failure tolerance data from the literature. The leg
      and thigh models' structural and contact parameters were simultaneously optimized
      to validate model response in simulations replicating previous dynamic bending
      experiments. The aggregate model's full-scale kinematic response was verified by
      comparing 3-D local (knee bending angles) and global (linear accelerations and
      velocities) frame leg and thigh kinematics from vehicle impact simulations with
      data generated from seven vehicle-pedestrian (PMHS) impact experiments. RESULTS:
      By optimizing contact and structural response variables, the applied moment vs.
      deflection response of the leg and thigh showed excellent correlation with the
      experimental corridor averages in component-level bending simulations. The full
      scale kinematic response of the 50th percentile male model showed good
      correlation with the PMHS response data in both the rate of valgus knee bending
      (approximately 3 degress/ms) and in the timing and magnitude of the peak thigh
      and leg accelerations (250 g and 400 g). Additionally, as a result of vehicle
      interaction, both the model and the experiments showed that the thigh and leg are
      initially accelerated upward (100 g) and downward (100 g), respectively, and then
      downward (60 g) and upward (100 g), respectively. The model also predicted a
      valgus knee injury and a tibia fracture similar to those seen in the PMHS.
      CONCLUSIONS: The use of a facet surface model of the lower extremity skin and
      simultaneous optimization of the model's structural response and contact
      parameters resulted in a model capable of accurately predicting the detailed
      kinematic response of the lower extremity under vehicle impact loading at 40
      km/h. The model can be scaled to represent varying pedestrian anthropometries and
      can assess the risks associated with sustaining the most common pedestrian
      injuries. As a vehicle design tool, the model can be used to optimize front-end
      designs, or it can be used in combination with a detailed FEM to reduce the vast
      design space prior to FE simulations. Additionally, the model can be used as a
      tool to study pedestrian impact kinematics, real-world case reconstructions, or
      particular vehicle countermeasures.

PMID- 19593719
TI  - Positive nasal culture of methicillin-resistant Staphylococcus aureus (MRSA) is a
      risk factor for surgical site infection in orthopedics.
AB  - BACKGROUND: Although nasal carriage of MRSA has been identified as one of the
      risk factors for surgical site infection (SSI) with MRSA, there have been no
      reports of this in the orthopedics field. METHODS: This prospective observational
      cohort study included 2,423 consecutive patients who were admitted to our
      department over 26 months and who underwent orthopedic surgery. We examined the
      relationship between pre-existing nasal MRSA and subsequent occurrence of SSI
      with MRSA. RESULTS: 63 patients (2.6%) had a positive nasal MRSA culture. 15
      patients (0.6%) developed SSI with MRSA. The occurrence of SSI with MRSA in nasal
      MRSA carriers was significantly higher than that in non-carriers (4 out of 63
      (6.3%) vs. 11 out of 2,360 (0.5%); p < 0.001) (adjusted OR: 11; 95% CI: 3-37; p =
      0.001). INTERPRETATION: We recommend appropriate treatment of patients who are
      nasal carriers of MRSA before orthopedic surgery.

PMID- 19593720
TI  - The mechanism of primary patellar dislocation: trauma history of 126 patients.
AB  - BACKGROUND AND PURPOSE: Several mechanisms are responsible for patellar
      dislocation. We investigated how the primary pathomechanism relates to patient
      characteristics and the outcome. METHODS: 126 patients (81 females) with primary
      patellar dislocation reported the knee position before the episode, the movement
      during it, and whether the patella was locked in dislocation. The median age was
      20 (9-47) years. The subjective outcome and Kujala, Hughston VAS, and Tegner
      scores were evaluated after an average of 7 years. RESULTS: 102 patients moved to
      flexion during the dislocation, 98 from a straight start and 4 from a well-bent
      start. 10 extended the knee from a well-bent start; they were older (mean 25 vs.
      19 years) and more often had low trauma energy (5/10 vs. 15/102) and a locked
      dislocation (10/10 vs. 50/102). 4 had a direct hit to the knee and 1 only rotated
      it while stretching. 24 of 60 patients with open growth line of the tibial
      tubercle and 43 of 66 with closed tubercle had locked primary dislocation (p =
      0.005). 33% of girls, 52% of boys, 57% of women, and 71% of men had locked
      primary dislocation. There was no correlation between trauma mechanism and
      outcome. INTERPRETATION: Movement to flexion occurred in 84% of primary patellar
      dislocations and movement to extension in 8%. Spontaneous patellar relocation is
      common in skeletally immature girls and locked dislocation is common in
      skeletally mature men.

PMID- 19593721
TI  - Differences in hip bone mineral density may explain the hip fracture pattern in
      osteoarthritic hips.
AB  - INTRODUCTION: In patients with osteoarthritis of the hip (OAH), trochanteric
      fractures are much more common than femoral neck fractures. One reason may be
      altered bone composition in the proximal femurs. OAH often leads to a fixed
      external rotation of the hip, leading to difficulties in positioning during DXA
      measurements. We compared BMD in OAH-affected legs and healthy legs. PATIENTS AND
      METHODS: 40 patients with strictly unilateral OAH were cross-sectionally
      investigated with DXA at the hips and heels bilaterally as well as body
      composition of the legs. 3 regions of interest in the proximal femur were
      measured: femoral neck (FN), trochanter (TR), and total hip (TH). The design of
      the study allowed us to perform paired t-test between the OAH side and the
      healthy side. RESULTS: BMD was increased by 4.1% in FN, and reduced by 8.3% in TR
      and 4.1% in TH (p < 0.001 for all comparisons). INTERPRETATION: The differences
      in BMD, with decrease in the trochanter and increase in the femoral neck, may
      offer an explanation for the pattern of hip fractures seen in osteoarthritis.
      External rotation of the hip cannot explain the differences in BMD.

PMID- 19593722
TI  - Distal femoral stem-bone anchorage of a cementless revision total hip
      arthroplasty: evaluation of 14 patients by CT.
AB  - BACKGROUND AND PURPOSE: According to the manual of the cementless Link MP
      reconstruction prosthesis, a distal femoral stem-bone anchorage of at least 80 mm
      is necessary to gain implant stability. There have been no in vivo studies
      showing that this distance is either achieved in clinical practice or needed for
      clinically satisfying results. Thus, we assessed the femoral stem-bone anchorage
      of the MP prosthesis using CT. METHODS: 14 patients with the MP stem were
      evaluated by CT scans at a median follow-up time of 12 months postoperatively.
      Femoral stem-bone anchorage was defined as adequate if 50% of the stem flutes or
      more had cortical bone contact. The length of anchorage was derived from the
      number of slices with adequate anchorage. Clinical outcome was assessed with VAS
      for pain and Harris hip score (HHS), both at 1 and 5 years of follow-up. RESULTS:
      The median length of stem-bone anchorage was 33 mm (interquartile range 10-60),
      which was shorter than recommended (p = 0.002). Still, at the 1-year control, all
      patients were fully weight-bearing and only 1/14 complained about mild thigh
      pain. 7/14 patients did not experience any pain in the affected hip. The patients
      had a median of 85 points in the HHS. The clinical outcome at 5 years was
      unchanged. INTERPRETATION: We found that it can be difficult to achieve a stem
      bone anchorage of at least 80 mm for the MP Link prosthesis. However, this does
      not appear to be necessary to obtain stability and to achieve clinically
      satisfying results.

PMID- 19593723
TI  - Hereditary hemochromatosis: a neglected diagnosis in orthopedics: a series of 7
      patients with ankle arthritis, and a review of the literature.

PMID- 19593724
TI  - C-reactive protein levels after 4 types of arthroplasty.
AB  - BACKGROUND AND PURPOSE: Postoperative C-reactive protein (CRP) levels in serum
      appear to reflect surgical trauma. We examined CRP levels after 4 types of
      arthroplasty. MATERIAL AND METHODS: We investigated 102 patients who had total
      knee arthroplasty (TKA), computer navigation-assisted total knee arthroplasty
      (NAV-TKA), hip resurfacing arthroplasty (metal on metal, MMSA) and total hip
      arthroplasty (THA), respectively. CRP levels were estimated before surgery and
      postoperatively at 2 and 7 days. RESULTS: Postoperatively, the peak CRP levels
      were highest on the second day after surgery in each of the groups. The peak CPR
      levels after hip resurfacing were lower than those after conventional primary
      THA. The peak CRP levels after computer navigation-assisted TKA were lower than
      those after conventional primary TKA. INTERPRETATION: The extent of bone and bone
      marrow injury rather than the region of surgery or the amount of soft tissue
      damage appears to determine the extent of the postoperative CRP response.

PMID- 19593725
TI  - Association of maternally inherited GNAS alleles with African-American male birth
      weight.
AB  - OBJECTIVE: Human birth weight variation has a significant genetic component and
      important clinical consequences. We performed a survey of single nucleotide
      polymorphisms (SNPs) in 14 candidate genes to identify associations with birth
      weight variation. METHODS: SNP variation was surveyed in 221 healthy African
      American mother-newborn pairs. Genes were selected based on previous association
      with obesity-related traits, significant differences in circulating protein
      levels in low birth weight pregnancies or association with newborn size in model
      organisms or growth disorders in humans. Association was tested via multiple
      linear regression with adjustment for significant covariables. RESULTS: Under a
      dominant model SNP rs7754561 of ENPPI was significantly associated with birth
      weight. Among imprinted loci, maternal genotypes for SNP rs6026576 of GNAS were
      significantly associated with birth weight (additive and dominant models). This
      association was restricted to male offspring. Analyses that distinguished between
      alleles of paternal and maternal origin demonstrated that only maternally
      transmitted alleles were associated with birth weight and that this association
      was restricted to male newborns. CONCLUSION: The effect of only maternally
      transmitted alleles of GNAS may be a consequence of the complex splicing and
      imprinting pattern of the GNAS gene, although the reason this effect is observed
      only among male newborns is unclear.

PMID- 19593726
TI  - Tracking of cardiometabolic risk factor clustering from childhood to adulthood.
AB  - Cardiometabolic risk factor clustering is predictive of future cardiovascular
      disease. If clustering of risk factors is a stable characteristic from childhood
      to adulthood, then intervention in high-risk children may provide an early
      opportunity to decrease the progression to overt cardiovascular disease outcomes.
      Thus, the purpose of this paper was to review the evidence for risk factor
      clustering being a stable characteristic from childhood to adulthood. Seven
      articles were identified that met the inclusion criteria. Despite varying
      definitions of risk factor clustering and different methodologies for assessing
      tracking, the results generally showed stability of risk factor clustering from
      childhood into adulthood. Inter-age correlations of risk factor cluster scores
      ranged from 0.42 to 0.67, and the proportions of individuals remaining in the
      upper quantiles of risk over time were significantly greater than predicted by
      chance alone. Future studies are needed to elucidate the effects of gender,
      ethnicity, and lifestyle behaviors on the tracking of risk factor clustering.

PMID- 19593727
TI  - The PedsQL multidimensional fatigue scale in pediatric obesity: feasibility,
      reliability and validity.
AB  - OBJECTIVE: The PedsQL (Pediatric Quality of Life Inventory) is a modular
      instrument designed to measure health-related quality of life (HRQOL) and disease
      specific symptoms in children and adolescents. The PedsQL Multidimensional
      Fatigue Scale was designed as a child self-report and parent proxy-report generic
      symptom-specific instrument to measure fatigue in pediatric patients. The
      objective of the present study was to determine the feasibility, reliability, and
      validity of the PedsQL Multidimensional Fatigue Scale in pediatric obesity.
      METHODS: The 18-item PedsQL Multidimensional Fatigue Scale (General Fatigue,
      Sleep/Rest Fatigue, and Cognitive Fatigue domains) and the PedsQL 4.0 Generic
      Core Scales were completed by 41 pediatric patients with a physician-diagnosis of
      obesity and 43 parents from a hospital-based Pediatric Endocrinology Clinic.
      RESULTS: The PedsQL Multidimensional Fatigue Scale evidenced minimal missing
      responses (1.6%, child report; 0.5%, parent report), achieved excellent
      reliability for the Total Fatigue Scale Score (alpha = 0.90 child report, 0.90
      parent report), distinguished between pediatric patients with obesity and healthy
      children, and was significantly correlated with the PedsQL 4.0 Generic Core
      Scales supporting construct validity. Pediatric patients with obesity experienced
      fatigue comparable with pediatric patients receiving cancer treatment,
      demonstrating the relative severity of their fatigue symptoms. CONCLUSIONS: The
      results demonstrate the measurement properties of the PedsQL Multidimensional
      Fatigue Scale in pediatric obesity. The findings suggest that the PedsQL
      Multidimensional Fatigue Scale may be utilized in the standardized evaluation of
      fatigue in pediatric patients with obesity.

PMID- 19593728
TI  - Human adenovirus-36 antibody status is associated with obesity in children.
AB  - BACKGROUND: Human adenovirus-36 (Ad-36) is thought to induce obesity by a direct
      effect of the viral E4orf1 gene on lipogenic enzymes in host adipocytes. Ad-36
      prevalence is 30% in obese adults, but prevalence has not been reported in
      childhood obesity. OBJECTIVES: To determine the prevalence of Ad-36 infection in
      obese Korean children (age 14.8 +/- 1.9; range 8.3-6.3 years); correlation of
      infection with BMI z-score and other obesity measures. METHODS: Blood was drawn
      at the annual school physical exam or clinic visit; Ad-36 status was determined
      by serum neutralization assay; and routine serum chemistry values. RESULTS: A
      total of 30% of subjects were positive (N = 25) for Ad-36; 70% were negative (N =
      59). Significantly higher BMI z-scores (1.92 vs. 1.65, p < 0.01) and waist
      circumferences (96.3 vs. 90.7 cm, p = 0.05) were found in infected versus
      uninfected children. Cardiovascular risk factors were not significantly
      different. CONCLUSIONS: Ad-36 infection is common in obese Korean children and
      correlates highly with obesity. Ad-36 may have played a role in the obesity and
      Type 2 diabetes epidemic in children.

PMID- 19593729
TI  - Anatomic imaging of gluteal perforator flaps without ionizing radiation: seeing
      is believing with magnetic resonance angiography.
AB  - Preoperative imaging is essential for abdominal perforator flap breast
      reconstruction because it allows for preoperative perforator selection, resulting
      in improved operative efficiency and flap design. The benefits of visualizing the
      vasculature preoperatively also extend to gluteal artery perforator flaps.
      Initially, our practice used computed tomography angiography (CTA) to image the
      gluteal vessels. However, with advances in magnetic resonance imaging angiography
      (MRA), perforating vessels of 1-mm diameter can reliably be visualized without
      exposing patients to ionizing radiation or iodinated intravenous contrast. In our
      original MRA protocol to image abdominal flaps, we found the accuracy of MRA
      compared favorably with CTA. With our increased experience with MRA, we decided
      to use MRA to image gluteal flaps. Technical changes were made to the MRA
      protocol to improve image quality and extend the field of view. Using our new MRA
      protocol, we can image the vasculature of the buttock, abdomen, and upper thigh
      in one study. We have found that the spatial resolution of MRA is sufficient to
      accurately map gluteal perforating vessels, as well as provide information on
      vessel caliber and course. This article details our experience with preoperative
      imaging for gluteal perforator flap breast reconstruction.

PMID- 19593730
TI  - A review of local and regional flaps for distal leg reconstruction.
AB  - Reconstruction of defects or wounds of the distal third of the leg with exposed
      bone, tendon, or hardware is challenging. Free tissue transfer has allowed limb
      salvage in many cases but requires a relatively healthy and stable patient, long
      operative times, and a significant expense. Small and moderate-size wounds of the
      distal leg may be better served by the use of local and regional flaps. Due to a
      better understanding of leg vascular anatomy and angiosomes, as well as more
      sophisticated and varied flap designs, local and regional flaps have been
      described and successfully used in distal leg wounds. The goal is choosing the
      most appropriate flap given the patient's anatomy and wound characteristics. The
      following review will detail the available local and regional flaps for
      reconstruction of the distal third of the leg with an emphasis on decision
      making, anatomy, flap design, and technique.

PMID- 19593732
TI  - Outcomes of microvascular reconstruction of single-vessel lower extremities: limb
      salvage versus amputation.
AB  - Many patients with complex wounds on single-vessel lower extremities undergo
      amputation. Limb salvage using microvascular reconstructive techniques is an
      alternative in these patients that can preserve ambulatory status, but data
      focused on reconstruction in the single vessel population have been limited. A
      retrospective review of all microvascular lower-extremity reconstructions from
      August 2003 to December 2008 was performed. Forty-two patients were identified,
      of which 10 were found to have a complex wound and single-vessel perfusion to the
      affected extremity. Patient charts were reviewed for age, sex, medical
      comorbidities, mechanism of injury (traumatic versus nontraumatic), wound
      location, flap type, complications, flap outcome, and limb salvage outcome. All
      10 flaps were successful (100%), and long-term limb salvage was 90%. Mean follow
      up was 20.4 months. There were two complications, a hematoma and a case of flap
      success followed by reactivation of osteomyelitis 3 months after the free flap
      procedure resulting in below-knee amputation. The ultimate goal of limb salvage
      is to maximize limb length in an effort to prevent an increase in the energy of
      ambulation. Using microvascular reconstructive techniques, it can be performed
      successfully and with the majority of patients regaining an ambulatory status.

PMID- 19593731
TI  - Changes in blood velocity following microvascular free tissue transfer.
AB  - Understanding how pedicle blood velocities change after free tissue transfer may
      enable microvascular surgeons to predict when thrombosis is most likely to occur.
      A 20-MHz Doppler probe was used to measure arterial and venous blood velocities
      prior to pedicle division and 20 minutes after anastomosis in 32 microvascular
      free flaps. An implantable Doppler probe was then used to measure arterial and
      venous blood velocities daily for 5 days. Peak arterial blood velocity averaged
      30.6 cm/s prior to pedicle division and increased to 36.5 cm/s 20 minutes after
      anastomosis ( P < 0.05). Peak venous blood velocity averaged 7.6 cm/s prior to
      pedicle division and increased to 12.4 cm/s 20 minutes after anastomosis ( P <
      0.05). Peak arterial blood velocities averaged 34.0, 37.7, 43.8, 37.9, 37.6 cm/s
      on postoperative days (PODs) 1 through 5, respectively. Peak venous blood
      velocities averaged 11.9, 14.5, 18.2, 16.8, 17.7 cm/s on PODs 1 through 5,
      respectively. The peak arterial blood velocity on POD 3, and peak venous blood
      velocities on PODs 2, 3, and 5 were significantly higher than 20 minutes after
      anastomosis ( P < 0.05). Arterial and venous blood velocities increase for the
      first 3 postoperative days, potentially contributing to the declining risk for
      pedicle thrombosis during this time period.

PMID- 19593733
TI  - Does chosen approach to the inguinal canal affect the outcome of hernial repair?
AB  - Access to the posterior inguinal wall is a fundamental part of inguinal hernia
      repair. The approach to the inguinal canal may affect the course and outcome of
      the operation. The aim of this study is to compare posterior approach (PA) repair
      with the standard anterior approach (AA). The study included 91 low-risk
      unilateral primary inguinal hernia patients who randomly received AA repair or PA
      repair. Various outcome measures in both groups were compared, and the mean
      operating time was longer for the AA repair group. Intra-operative complications
      were the same in both groups. Postoperative complications were more frequent in
      the AA repair group. The at-rest mean visual analog score (VAS), 24 hours
      postoperatively, seemed to be higher in the AA repair group. AA patients were
      able to postoperatively walk sooner than PA patients. Inguinal hernia repair
      through a PA seems to be less painful, less debilitating, and more easily
      applicable than the AA. Such advantages may be the reasons to select it as a
      standard procedure of choice.

PMID- 19593734
TI  - Different apoptotic responses of human and bovine pericytes to fluctuating
      glucose levels and protective role of thiamine.
AB  - BACKGROUND: Vascular cells in diabetes are subjected to daily fluctuations from
      high to low glucose. We aimed at investigating whether pulsed exposure to
      different glucose concentrations influences apoptosis in human retinal pericytes
      (HRP) versus bovine retinal pericytes (BRP), with consequences on the onset of
      diabetic retinopathy, and the possible protective role of thiamine. METHODS: BRP
      and HRP (wild-type and immortalized) were grown in physiological/high glucose for
      7 days, and then returned to physiological glucose for another 24, 48 or 72 h.
      Cells were also kept intermittently at 48-h intervals in high/normal glucose for
      8 days, with/without thiamine/benfotiamine. Apoptosis was determined through
      ELISA, TUNEL, Bcl-2, Bax and p53 expression/concentration. RESULTS: Continuous
      exposure to high glucose increased apoptosis in BRP, but not HRP. BRP apoptosis
      normalized within 24 h of physiological glucose re-entry, while HRP apoptosis
      increased within 24-48 h of re-entry. Intermittent exposure to high glucose
      increased apoptosis in HRP and BRP. Bcl-2/Bax results were consistent with DNA
      fragmentation, while p53 was unchanged. Thiamine and benfotiamine countered
      intermittent high glucose-induced apoptosis. CONCLUSIONS: Human pericytes are
      less prone to apoptosis induced by persistently high glucose than bovine cells.
      However, while BRP recover after returning to physiological levels, HRP are more
      vulnerable to both downwardly fluctuating glucose levels and intermittent
      exposure. These findings reinforce the hypotheses that (1) glycaemic fluctuations
      play a role in the development of diabetic retinopathy and (2) species-specific
      models are needed. Thiamine and benfotiamine prevent human pericyte apoptosis,
      indicating this vitamin as an inexpensive approach to the prevention and/or
      treatment of diabetic complications.

PMID- 19593735
TI  - Effects of robotic-aided rehabilitation on recovery of upper extremity function
      in chronic stroke: a single case study.
AB  - The objective of the study was to examine the results of robotic therapy in a
      single client. A 48-year-old female client 15 months post-stroke, with right
      hemiparesis, received robotic therapy as an outpatient in a large Midwestern
      rehabilitation hospital. Robotic therapy was provided three times a week for 6
      weeks. Robotic therapy consisted of goal-directed, robotic-aided reaching tasks
      to exercise the hemiparetic shoulder and elbow. No other therapeutic intervention
      for the affected upper extremity was provided during the study or 3 months follow
      up period. The outcome measures included the Fugl-Meyer, graded Wolf motor
      function test (GWMFT), motor activity log, active range of motion and Canadian
      occupational performance measure. The participant made gains in active movement;
      performance; and satisfaction of functional tasks, GWMFT and functional use.
      Limitations involved in this study relate to the generalizability of the sample
      size, effect of medications, expense of robotic technologies and the impact of
      aphasia. Future research should incorporate functional use training along with
      robotic therapy.

PMID- 19593736
TI  - Bioanalytical LC-MS/MS method validation for plasma determination of topiramate
      in healthy Indian volunteers.
AB  - A LC-MS/MS method for plasma topiramate analysis is delineated involving least
      number of healthy volunteers. Topiramate and amlodipine internal standard (IS)
      were extracted by simple centrifuge-coupled solid-phase extraction and reverse
      phase chromatographic separation was performed on an Ascentis C(18) column. Turbo
      spray negative-ion mode multiple-reaction monitoring was selected for mass pair
      detection at m/z 338.3 --> 78.0 and m/z 407.3 --> 295.5 for analyte and IS
      respectively. The method showed a dynamic linearity range from 10.4 to 2045.0
      ng/mL, lower limit of quantitation achieved at 10.4 ng/mL and finally a mass
      spectrometric total run time of within 2.5 min for human sample analysis.
      Bioequivalence was assessed successfully using this fully validated method on 16
      fasted Indian male subjects with 25 mg topiramate tablet administration. An
      appropriate study design describes plasma samples collection up to 216 h post
      dose in two periods, separated by a 28 day washout period. The challenge of half
      life matching for test and reference drug was achieved with 73.43 +/- 9.68 and
      73.06 +/- 14.03 h, respectively, and intra-subject coefficient of variation
      achieved within 11% for AUCs and C(max) evaluated by non-compartmental
      pharmacokinetic analysis. The results of LCMS topiramate complete method
      validation supported by pharmacokinetic study have not been published before, and
      are presented and discussed for the first time in this article.

PMID- 19593737
TI  - Sodium, blood pressure, and ethnicity: what have we learned?
AB  - An enormous amount of research has yielded significant knowledge about ethnic
      differences in sodium homeostasis and blood pressure regulation. Consistent
      findings such as greater sodium-sensitivity, lower potassium excretion and high
      higher serum sodium levels in African Americans need further exploration to
      define more precise physiological mechanisms. The genetic alleles associated with
      sodium homeostasis in relation to blood pressure have accounted for only a small
      proportion of the variance in blood pressure. Several allelic variants differ in
      frequency among ethnic groups and heat-adapted genetic variants have a high
      prevalence in low latitudes and hot, wet climates which lends support to the
      "sodium retention" hypothesis. The blood pressure disparities between African
      Americans and whites may, in part, be due to different allelic frequencies of
      genes associated with sodium homeostasis. However, with advances in genomics,
      environmental factors tend to be neglected in research. Better measures of
      environmental stress have recently been developed by anthropologists and should
      be included in research designs by investigators in other disciplines. Public
      health efforts should encourage food producers to reduce sodium content of its
      products, and physicians should encourage patients to reduce consumption of high
      sodium packaged and fast foods.

PMID- 19593738
TI  - Autosomal and X chromosome Alu insertions in Bolivian Aymaras and Quechuas: two
      languages and one genetic pool.
AB  - Thirty-two polymorphic Alu insertions (18 autosomal and 14 from the X chromosome)
      were studied in 192 individuals from two Amerindian populations of the Bolivian
      Altiplano (Aymara and Quechua speakers: the two main Andean linguistic groups),
      to provide relevant information about their genetic relationships and demographic
      processes. The main objective was to determine from genetic data whether the
      expansion of the Quechua language into Bolivia could be associated with
      demographic (Inca migration of Quechua-speakers from Peru into Bolivia) or
      cultural (language imposition by the Inca Empire) processes. Allele frequencies
      were used to assess the genetic relationships between these two linguistic
      groups. Our results indicated that the two Bolivian samples showed a high genetic
      similarity for both sets of markers and were clearly differentiated from the two
      Peruvian Quechua samples available in the literature. Additionally, our data were
      compared with the available literature to determine the genetic and linguistic
      structure, and East-West differentiation in South America. The close genetic
      relationship between the two Bolivian samples and their differentiation from the
      Quechua-speakers from Peru suggests that the Quechua language expansion in
      Bolivia took place without any important demographic contribution. Moreover, no
      clear geographical or linguistic structure was found for the Alu variation among
      South Amerindians.

PMID- 19593739
TI  - The health of Arctic populations: Does cold matter?
AB  - The objective of the study was to examine whether cold climate is associated with
      poorer health in diverse Arctic populations. With climate change increasingly
      affecting the Arctic, the association between climate and population health
      status is of public health significance. The mean January and July temperatures
      were determined for 27 Arctic regions based on weather station data for the
      period 1961-1990 and their association with a variety of health outcomes assessed
      by correlation and multiple linear regression analyses. Mean January temperature
      was inversely associated with infant and perinatal mortality rate, age
      standardized mortality rate from respiratory diseases, and age-specific fertility
      rate for teens and directly associated with life expectancy at birth in both
      males and females, independent of a variety of socioeconomic, demographic, and
      health care factors. Mean July temperature was also associated with infant
      mortality and mortality from respiratory diseases, and with total fertility rate.
      For every 10 degrees C increase in mean January temperature, the life expectancy
      at birth among males increased by about 6 years and infant mortality rate
      decreased by about 4 deaths/1,000 livebirths. Cold climate is significantly
      associated with higher mortality and fertility in Arctic populations and should
      be recognized in public health planning.

PMID- 19593740
TI  - Metric and nonmetric dental variation and the population structure of the Ainu.
AB  - Gene flow and genetic drift are important factors affecting geographic variations
      in human phenotypic traits. In the present study, the effects of gene flow from
      an outside source on the pattern of within- and among-group variation of the Ainu
      from Sakhalin Island and three local groups of Hokkaido are examined by applying
      an R-matrix approach to metric and nonmetric dental data. The comparative samples
      consist of their ancestral and neighboring populations, such as the Neolithic
      Jomon, the subsequent Epi-Jomon/Satsumon, the Okhotsk culture people who migrated
      from Northeast Asia to the northeastern part of Hokkaido during a period 1600-900
      years B.P., and modern non-Ainu Japanese. The results obtained by using the
      census population sizes of the regional groups of the Ainu as an estimate of
      relative effective population size suggest the possibility of an admixture
      between the Okhotsk culture people and the indigenous inhabitants in Hokkaido, at
      least in the coastal region along the Sea of Okhotsk. Such gene flow from
      Northeast Asian continent may have exerted an effect on the genetic structure of
      the contemporary Ainu. The present findings indicate that the population
      structure, as represented by genetic drift and gene flow, tend to be obscured in
      the results obtained by standard statistical methods such as Mahalanobis'
      generalized distance and Smith's MMDs. The present extension of the R-matrix
      approach to metric and nonmetric dental data provide results that can be
      interpreted in terms of a genetically, archaeologically, and prehistorically
      suggested pattern of gene flow and isolation.

PMID- 19593741
TI  - Genetic profiling of the Azores Islands (Portugal): data from 10 X-chromosome
      STRs.
AB  - The populations from the Azores islands have been the target of several genetic
      studies, using data derived from monoparental and recombining genetic systems.
      These studies have provided a complex picture of the genetic landscape of the
      three groups of Azorean islands, and further data are required to assess its
      genetic profile. We present a study of the polymorphism in 10 X-chromosome STR
      loci (DSXS8378, DXS9898, DXS7133, GATA31E08, GATA172D05, DXS7423, DXS6809,
      DXS7132, DXS9902, DXS6789) conducted on a total of 304 chromosomes (97 females
      and 110 males) of unrelated individuals with Azorean ancestry. Average gene
      diversity was 74.47%, ranging from 66.21% (DXS7133) to 81.19% (GATA172D05). No
      shared haplotypes were found. Genotype frequencies among females displayed
      conformity with Hardy-Weinberg expectations for all loci. Pairwise linkage
      disequilibrium tests did not reveal evidences of association between the studied
      markers. Significant differences in allelic frequencies between the Western and
      the Eastern group of islands are in agreement with previous results from
      mitochondrial DNA and Y chromosome studies, providing further evidence that the
      Azores cannot be considered an homogeneous population. Moreover, differences
      between the Western group and the North of Portugal are also reported, supporting
      the pertinence of a specific database for the Azores populations, on what
      concerns the genetic markers analyzed.

PMID- 19593742
TI  - 18F-FDG uptake and its clinical relevance in primary gastric lymphoma.
AB  - We studied the clinical relevance of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake
      in patients with primary gastric lymphoma underwent positron emission tomography
      (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric
      lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10
      extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue
      (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic
      features, and the results of CT and endoscopy. Nine patients were up-staged based
      on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT
      lymphomas) while six patients were down-staged by the PET/CT scan. The standard
      uptake value (SUV) was used as an indicator of a lesion with a high metabolic
      rate. The high SUVmax group, defined as an SUVmax >or= median value, was
      significantly associated with an advanced Lugano stage (p < 0.001). Three
      patients with DLBCL, who showed an initially high SUVmax, died of disease
      progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was
      performed, 11 patients with ulcerative or mucosal lesions showed residual (18)F
      FDG uptake. All of these gastric lesions were grossly and pathologically benign
      lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be
      used in staging patients with primary gastric lymphoma; however, the residual
      (18)F-FDG uptake observed during follow-up should be interpreted cautiously and
      should be combined with endoscopy and multiple biopsies of the stomach.

PMID- 19593743
TI  - Two novel NPM1 mutations in a therapy-responder AML patient.
AB  - Nucleophosmin 1 (NPM1) is an abundant phosphoprotein mainly located in the
      nucleolus but also shuttling between the nucleus and cytoplasm. NPM1 has been
      proposed to be involved in synthesis and processing of ribosomal RNA, regulation
      of chromatin structure and transport of rRNA and ribosomal proteins. NPM1 gene is
      considered to be implicated in human cancer as it is a frequent target of genetic
      alterations, primarily in haematopoietic neoplasms. We describe a case of a
      therapy-responder acute myeloid leukaemia (AML) patient bearing two novel NPM1
      mutations. Cells' transfection studies indicate that the presence of one of these
      mutations is associated to an abnormal nucleolar structure, suggesting that NPM1
      may contribute to the control of nucleolar integrity.

PMID- 19593744
TI  - Experimental and clinical characteristics in myelodysplastic syndrome patients
      with or without HLA-DR15 allele.
AB  - We studied the effects of the presence of the HLA-DR15 allele on the experimental
      and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical
      data of 136 patients with MDS. We observed that the frequency of HLA-DR15
      expression in MDS patients (38.7%) was significantly higher than that in the
      healthy controls (p < 0.01). We noted the following observations with regard to
      disease progression: None of the 46 HLA-DR15 positive patients with international
      prognostic scoring system (IPSS) scores <or=1 developed acute myeloid leukaemia
      (AML) during the follow-up period, while six of the 63 DR15-negative patients
      with the same IPSS score developed AML within a shorter follow-up period (p =
      0.039). Furthermore, the incidence of poor chromosomal abnormalities, the
      percentage of patients with IPSS scores >or=1.5 and the presence of >or=5% blasts
      in the bone marrow in the DR15-positive patients were lower than the
      corresponding findings in the DR15-negative patients. In addition, we also
      recorded the following observations with regard to bone marrow (BM) failure: The
      bicytopenia/pancytopenia ratio in the DR15-positive patients was higher than that
      in the DR15-negative patients (92.4 vs. 78.3%; p = 0.029). The peripheral
      neutrophil count and the platelet count in the DR15-positive patients were lower
      than those in the DR15-negative patients (p = 0.028 and p = 0.011, respectively).
      Moreover, hypocellularity was more easily detectable in the DR15-positive
      patients (26.4 vs. 16.9%). In addition, the BM CD4+ lymphocyte count and the
      CD4/CD8 ratio in the DR15-positive patients were higher than the corresponding
      values in the DR15-negative patients (p < 0.05 for both). However, there were no
      significant differences between the polarization of T-helper (T(h)) and T
      cytotoxic (T(c)) cells and the cytokine levels in these two patient groups. We
      concluded that the presence of the HLA-DR15 allele is indicative of a genetic
      susceptibility to MDS and, the presence of the HLA-DR15 allele showed less
      association with disease progression and greater association with BM failure.

PMID- 19593745
TI  - Investigating the role of attachment in social comparison theories of eating
      disorders within a non-clinical female population.
AB  - OBJECTIVE: The present study aimed to integrate attachment theory and
      sociocultural theory as predictors of disordered eating, thereby combining two
      previously distinct literatures in order to provide a more comprehensive model of
      eating disorder development. It was specifically proposed that women's attachment
      style may influence their tendency to socially compare themselves to idealized
      others. METHOD: Participants (N = 213) were non-clinical female undergraduates.
      Sociocultural attitudes to appearance, social comparison, attachment and eating
      disorder symptomatology were assessed using self-report questionnaires. RESULTS:
      Consistent with the hypothesis, social comparison was found to mediate the
      relationship between attachment anxiety and disordered eating. In addition,
      attachment avoidance, was not significantly associated with either
      internalisation of cultural ideals or social comparison but was significantly
      related to eating psychopathology. CONCLUSION: The findings suggest that
      attachment anxiety and avoidance influence disordered eating via different
      pathways, with attachment anxiety specifically being implicated in sociocultural
      models of disordered eating.

PMID- 19593746
TI  - Bilateral sequential cochlear implantation in the congenitally deaf child:
      evidence to support the concept of a 'critical age' after which the second ear is
      less likely to provide an adequate level of speech perception on its own.
AB  - This study attempts to answer the question of whether there is a 'critical age'
      after which a second contralateral cochlear implant is less likely to provide
      enough speech perception to be of practical use. The study was not designed to
      predict factors that determine successful binaural implant use, but to see if
      there was evidence to help determine the latest age at which the second ear can
      usefully be implanted, should the first side fail and become unusable.Outcome
      data, in the form of speech perception test results, were collected from 11
      cochlear implant programmes in the UK and one centre in Australia. Forty-seven
      congenitally bilaterally deaf subjects who received bilateral sequential implants
      were recruited to the study. The study also included four subjects with
      congenital unilateral profound deafness who had lost all hearing in their only
      hearing ear and received a cochlear implant in their unilaterally congenitally
      deaf ear. Of those 34 subjects for whom complete sets of data were available, the
      majority (72%) of those receiving their second (or unilateral) implant up to the
      age of 13 years scored 60 per cent or above in the Bamford Kowal Bench (BKB)
      sentence test, or equivalent. In contrast, of those nine receiving their second
      or unilateral implant at the age of 15 or above, none achieved adequate levels of
      speech perception on formal testing: two scored 29 per cent and 30 per cent,
      respectively, and the rest seven per cent or less.A discriminant function
      analysis performed on the data suggests that it is unlikely that a second
      contralateral implant received after the age of 16 to 18 years will, on its own,
      provide adequate levels of speech perception. As more children receive sequential
      bilateral cochlear implants and the pool of data enlarges the situation is likely
      to become clearer.The results provide support for the concept of a 'critical age'
      for implanting the second ear in successful congenitally deaf unilateral cochlear
      implant users. This would argue against 'preserving' the second ear beyond a
      certain age, in order to use newer models of cochlear implant or for the purpose
      of hair cell regeneration and similar procedures in the future. The results
      suggest a new and more absolute reason for bilateral implantation of congenitally
      deaf children at an early age.

PMID- 19593747
TI  - COX-2 inhibitors: complex association with lower risk of hospitalization for
      gastrointestinal events compared to traditional NSAIDs plus proton pump
      inhibitors.
AB  - PURPOSE: To compare hospitalization rates for serious upper and lower
      gastrointestinal (GI) events between chronic and acute users of a traditional non
      steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and
      users of a COX-2 selective inhibitor (Coxib). METHODS: The PHARMO Record Linkage
      System, including linked drug-dispensing and hospital records of approximately 3
      million individuals in the Netherlands was used. We selected new Coxib or tNSAID
      users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID
      dispensing and > or =1 year follow-up ending at the first hospitalization for GI
      event (the outcome), last dispensing, or end of the study period. Chronic users
      were patients who used any NSAIDs for > or =60 days during the first year (n = 58
      770); others were acute users (n = 538 420). Multivariate analysis was performed
      by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID
      and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents,
      anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease.
      RESULTS: The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib
      users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/-
      17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138
      +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence
      Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI
      events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were
      0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events.
      CONCLUSIONS: Coxib users had significantly lower rates of GI events. Further
      research should elucidate the possible impact of selection bias.

PMID- 19593748
TI  - Forty keratin-associated beta-proteins (beta-keratins) form the hard layers of
      scales, claws, and adhesive pads in the green anole lizard, Anolis carolinensis.
AB  - Using bioinformatic methods we have detected the genes of 40 keratin-associated
      beta-proteins (KAbetaPs) (beta-keratins) from the first available draft genome
      sequence of a reptile, the lizard Anolis carolinensis (Broad Institute, Boston).
      All genes are clustered in a single but not yet identified chromosomal locus, and
      contain a single intron of variable length. 5'-RACE and RT-PCR analyses using RNA
      from different epidermal regions show tissue-specific expression of different
      transcripts. These results were confirmed from the analysis of the A.
      carolinensis EST libraries (Broad Institute). Most deduced proteins are 12-16 kDa
      with a pI of 7.5-8.5. Two genes encoding putative proteins of 40 and 45 kDa are
      also present. Despite variability in amino acid sequences, four main subfamilies
      can be described. The largest subfamily includes proteins high in glycine, a
      small subfamily contains proteins high in cysteine, a third large subfamily
      contains proteins high in cysteine and glycine, and the fourth, smallest
      subfamily comprises proteins low in cysteine and glycine. An inner region of high
      amino acid identity is the most constant characteristic of these proteins and
      maps to a region with two to three close beta-folds in the proteins. This beta
      fold region is responsible for the formation of filaments of the corneous
      material in all types of scales in this species. Phylogenetic analysis shows that
      A. carolinensis KAbetaPs are more similar to those of other lepidosaurians
      (snake, lizard, and gecko lizard) than to those of archosaurians (chick and
      crocodile) and turtles.

PMID- 19593749
TI  - Chemical gradient-mediated melting curve analysis for genotyping of SNPs.
AB  - This report describes a microfluidic solid-phase chemical gradient-mediated
      melting curve analysis method for SNP analysis. The method is based on allele
      specific denaturation to discriminate mismatched (MM) from perfectly matched (PM)
      DNA duplexes upon exposure to linear chemical gradient. PM and MM DNA duplexes
      conjugated on beads are captured in a microfluidic gradient generator device
      designed with dams, keeping the beads trapped perpendicular to a gradient
      generating channel. Two denaturants, formamide and urea, were tested for their
      ability to destabilize the DNA duplex by competing with Watson-Crick pairing.
      Upon exposure to the chemical gradient, rapid denaturing profile was monitored in
      real time using fluorescence microscopy. The results show that the two duplexes
      exhibit different kinetics of denaturation profiles, enabling discrimination of
      MM from PM DNA duplexes to score SNP.

PMID- 19593750
TI  - Combinatorial peptide ligand libraries for urine proteome analysis: investigation
      of different elution systems.
AB  - Proteome treatments with peptide libraries in view of reducing high-abundance
      proteins and increasing the concentration of rare species involve the adsorption
      on solid-phase material. Subsequent elution of captured proteins may not be fully
      effective except when sequences of eluting agents are used. The standard way
      utilized up to the present has been a three- to four-step, sequential elution
      system consisting of various agents mixed together such as urea, thiourea, CHAPS,
      sodium chloride, citric or acetic acid and some polar solvents such as ACN and
      isopropanol. Elution sequences produce distinct fractions adding to the burden of
      having to analyze all of them. An alternative, highly effective, single elution
      to reduce the workload is here reported for the first time, namely elution in
      boiling 10% SDS added with 3% DTE. This single step elutes almost quantitatively
      the adsorbed proteins, thus ensuring, for all practical purposes, a full
      recovery. This high efficiency is believed to be due to the fact that the SDS
      micelles bury the polypeptide chains within their hydrophobic core, thus
      shielding them from the surroundings and impeding accidental adsorption to
      surfaces. Suggestions for selecting the best method to eliminate the excess of
      SDS for further protein analysis are also evaluated. The merits and limits of
      this novel system are assessed and discussed.

PMID- 19593751
TI  - Optimized protocol for the 2-DE of extracellular proteins from higher
      basidiomycetes inhabiting lignocellulose.
AB  - Basidiomycetes inhabiting lignocellulose comprise an important class of
      filamentous fungi with ecological and biotechnological relevance. Extracellular
      enzymes of wood-degrading fungi such as laccases, manganese-dependent (or
      independent) peroxidases, cellulases and xylanases are of considerable interest
      for biotechnological applications. Still, proteomic studies of fungal secretomes
      based on 2-DE can be very challenging due to low protein concentrations and
      variable amounts of fungal metabolites. Comparison of different standard methods
      for protein precipitation has demonstrated their limited applicability to fungal
      secretomes. The extracellular metabolites impair standard methods for protein
      quantification and can result in a strong overestimation of total protein. We
      have developed an optimized protocol for the precipitation of extracellular
      proteins from liquid cultures of Coprinopsis cinerea growing in an exponential
      phase on a complex media. We found that a considerable amount of gelatinous
      material can be removed from the liquid culture supernatants by high-speed
      centrifugation. Fungal proteins can be effectively enriched by TCA precipitation
      and coprecipitated metabolites hampering 2-DE can be removed through the
      application of Tris/acetone. Following our protocol makes it possible to
      concentrate proteins from culture supernatants and to simultaneously remove most
      of the impeding compounds from a given sample. We have applied this procedure in
      the 2-DE of secretomes from the model organism C. cinerea as well as other
      basidiomycetes such as Pleurotus ostreatus, Phanerochaete chrysosporium,
      Polyporus brumalis and Schizophyllum commune.

PMID- 19593753
TI  - Gold-catalyzed aerobic oxidation of 5-hydroxymethylfurfural in water at ambient
      temperature.
AB  - The aerobic oxidation of 5-hydroxymethylfurfural, a versatile biomass-derived
      chemical, is examined in water with a titania-supported gold-nanoparticle
      catalyst at ambient temperature (30  degrees C). The selectivity of the reaction
      towards 2,5-furandicarboxylic acid and the intermediate oxidation product 5
      hydroxymethyl-2-furancarboxylic acid is found to depend on the amount of added
      base and the oxygen pressure, suggesting that the reaction proceeds via initial
      oxidation of the aldehyde moiety followed by oxidation of the hydroxymethyl group
      of 5-hydroxymethylfurfural. Under optimized reaction conditions, a 71% yield of
      2,5-furandicarboxylic acid is obtained at full 5-hydroxymethylfurfural conversion
      in the presence of excess base.

PMID- 19593752
TI  - Charge-based characterization of nanometric cationic bifunctional
      maghemite/silica core/shell particles by capillary zone electrophoresis.
AB  - In view of employing functionalized nanoparticles (NPs) in the context of an
      immunodiagnostic, aminated maghemite/silica core/shell particles were synthesized
      so as to be further coated with an antibody or an antigen via the amino groups at
      their surface. Different functionalization rates were obtained by coating these
      maghemite/silica core/shell particles with 3-(aminopropyl)triethoxysilane and 2
      [methoxy(polyethyleneoxy)propyl]-trimethoxysilane at different molar ratios.
      Adequate analytical performances with CE coupled with UV-visible detection were
      obtained through semi-permanent capillary coating with didodecyldimethyl-ammonium
      bromide, thus preventing particle adsorption. First, the influence of
      experimental conditions such as electric field strength, injected particle amount
      as well as electrolyte ionic strength and pH, was evaluated. A charge-dependent
      electrophoretic mobility was evidenced and the separation selectivity was tuned
      according to electrolyte ionic strength and pH. The best resolutions were
      obtained at pH 8.0, high ionic strength (ca. 100 mM), and low total particle
      volume fraction (ca. 0.055%), thus eliminating interference effects between
      different particle populations in mixtures. A protocol derived from Kaiser's
      original description was performed for quantitation of the primary amino groups
      attached onto the NP surface. Thereafter a correlation between particle
      electrophoretic mobility and the density of amino groups at their surface was
      established. Eventually, CE proved to be an easy, fast, and reliable method for
      the determination of NP effective surface charge density.

PMID- 19593756
TI  - Determination of intrinsic monod kinetic parameters for two heterotrophic
      tetrachloroethene (PCE)-respiring strains and insight into their application.
AB  - A complete set of mathematically identifiable and meaningful kinetic parameters
      estimates is needed to accurately describe the activity of individual populations
      that dehalorespire tetrachloroethene (PCE) and other chlorinated ethenes. These
      data may be difficult to extract from the literature because kinetic parameter
      estimates obtained using mixed cultures may reflect the activity of multiple
      dehalorespiring populations, while those obtained at low initial substrate-to
      biomass ratios (S(0)/X(0)) are influenced by culture history and are generally
      not relevant to other systems. This study focused on estimation of electron donor
      and acceptor utilization kinetic parameters for the heterotrophic dehalorespirers
      Desulfuromonas michiganensis strain BB1 and Desulfitobacterium sp. strain PCE1.
      Electron acceptor utilization kinetic parameters that are identifiable and
      independent of culture history, i.e., intrinsic, could be estimated at S(0)/X(0)
      >or= 10, with both concentrations expressed as chemical oxygen demand (COD).
      However, the parameter estimates did not accurately describe dechlorination
      kinetics at lower S(0)/X(0) ratios. The maximum specific substrate utilization
      rates (q(max)) and half-saturation constants (K(S)) for PCE and trichloroethene
      (TCE) estimated for the two heterotrophic strains are higher than the values
      reported for Dehalococcoides cultures. These results suggest that the natural
      niche of Dehalococcoides strains that can metabolize a range of chlorinated
      ethenes may be to respire dichloroethene and vinyl chloride produced by
      Desulfuromonas and Desulfitobacterium strains or other populations that
      dechlorinate PCE and TCE at faster rates. Few data exist on the electron donor
      utilization kinetics of heterotrophic dehalorespirers. The results of this study
      suggest that Desulfuromonas and Desulfitobacterium strains should be able to
      compete for organic electron donors with other heterotrophic populations in the
      subsurface.

PMID- 19593757
TI  - Mathematical modeling of elution curves for a protein mixture in ion exchange
      chromatography applied to high protein concentration.
AB  - Protein elution curves in ion exchange chromatography (IEC) were simulated with a
      rate model. Three pure proteins and their mixture were used (alpha-lactalbumin,
      BSA, and conalbumin) under different operational conditions. The anionic matrix Q
      Sepharose FF was used packed in a 1 mL column. A high protein concentration (37.5
      mg/mL of total protein injected into the column) was used in order to extend the
      utility of the model. Mass transfer parameters were calculated using empiric
      correlations, where the axial dispersion was negligible (Pe > 300) and the mass
      transfer was controlled by the intraparticle diffusion (Bi > 10). The model
      assumes a modulator-eluite relationship were the equilibrium constant of the
      Langmuir isotherm was a function of salt concentration. Adsorption kinetic
      parameters were estimated from experimental data. The parameters for pure
      proteins were determined, and elution curves for changes in flow rate, ionic
      strength gradient, concentration, and sample size were predicted by the model.
      Then the kinetic parameters of the mixture were determined under the same
      operational conditions and some of the parameters had to be modified to take into
      account effects such as protein-protein interactions, competition, and
      displacement. Experimental elution curves obtained for changes in operational
      conditions such as flow rate and ionic strength gradient were simulated by the
      rate model for the protein mixture with a relative error in retention time of
      visible peaks <5%. IEC operational conditions and the peak fraction collection
      can be selected using a cost function of the production process which considers
      yield, purity, concentration, and process time that are obtained from
      simulations. Operational conditions that gave the minimum cost were selected.
      Simulations allows to diminish experimental time and cost.

PMID- 19593758
TI  - Do physical forces contribute to cryodamage?
AB  - To achieve the ultimate goal of both cryosurgery and cryopreservation, a thorough
      understanding of the processes responsible for cell and tissue damage is desired.
      The general belief is that cells are damaged primarily due to osmotic effects at
      slow cooling rates and intracellular ice formation at high cooling rates,
      together termed the "two factor theory." The present study deals with a third,
      largely ignored component--mechanical damage. Using pooled bull sperm cells as a
      model and directional freezing in large volumes, samples were frozen in the
      presence or absence of glass balls of three different diameters: 70-110, 250-500,
      and 1,000-1,250 microm, as a means of altering the surface area with which the
      cells come in contact. Post-thaw evaluation included motility at 0 h and after 3
      h at 37 degrees C, viability, acrosome integrity, and hypoosmotic swelling test.
      Interactions among glass balls, sperm cells, and ice crystals were observed by
      directional freezing cryomicroscopy. Intra-container pressure in relation to
      volume was also evaluated. The series of studies presented here indicate that the
      higher the surface area with which the cells come in contact, the greater the
      damage, possibly because the cells are squeezed between the ice crystals and the
      surface. We further demonstrate that with a decrease in volume, and thus increase
      in surface area-to-volume ratio, the intra-container pressure during freezing
      increases. It is suggested that large volume freezing, given that heat
      dissipation is solved, will inflict less cryodamage to the cells than the current
      practice of small volume freezing.

PMID- 19593759
TI  - Evaluation of the proximal tubular function in individuals with primary renal
      hypouricemia: an NMR-based metabonomic study.
AB  - Primary renal hypouricemia (PRH) refers to a rare condition of increased renal
      urate clearance, caused by an isolated inborn error of membrane transport of
      urate in the renal proximal tubule. Several cases of exercise-induced acute renal
      failure and urolithiasis have been reported. This is the first study that
      assessed tubular function in PRH using NMR-based metabonomic urine analysis. The
      study groups consisted of 36 unrelated asymptomatic subjects with PRH, defined as
      serum uric acid levels (sUA) <2.5 mg/dL and fractional excretion of uric acid
      (FEUA) >10%, after exclusion of diseases and drugs that may affect urate
      homeostasis, and 39 sex and age-matched healthy individuals with normal sUA
      levels (>4.0 mmol/L) and FEUA<10%. Individuals with primary hypouricemia
      presented similar biochemical profiles to the controls without significant
      differences with regard to FE of electrolytes and renal threshold for phosphate
      excretion. Individuals with primary hypouricemia were differentiated from healthy
      individuals in the orthogonal signal correction/partial least-squares
      discriminant analysis models of the NMR data with a statistically significant
      separation. The components that contributed to this separation were the lower
      levels of hippurate, creatinine, and trimethylaminoxide, and the higher levels of
      phenylalanine, alanine, glycine, glutamate, acetate, and of an unidentified
      metabolite (3.3 ppm) observed in hypouricemic subjects compared with controls.
      Primary hypouricemia, though considered an isolated renal tubular defect, is
      often associated with a more generalized proximal tubular disorder that mimics a
      partial Fanconi syndrome.

PMID- 19593761
TI  - N-acetyl resonances in in vivo and in vitro NMR spectroscopy of cystic ovarian
      tumors.
AB  - An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has
      frequently been found in the in vivo MR spectra of cancer patients. We
      demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of
      a patient with an ovarian tumor. (1)H-NMRS on the aspirated cyst fluid of this
      patient confirmed the observation. A complex of resonances was observed between
      2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples
      randomly chosen from our biobank. The resonance complex was significantly more
      prominent in samples from mucinous tumors than in samples from other histological
      subtypes. A macromolecule (>10 kDa) was found responsible for this complex of
      resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of
      two different types of bound sialic acid suggesting that N-glycans from
      glycoproteins and/or glycolipids cause this resonance complex. In the literature,
      plasma alpha-1 acid glycoprotein (AGP), known for its high content of N-linked
      glycans, has been suggested to contribute to the delta 2.0-2.1 spectral region.
      The AGP cyst fluid concentration did not correlate significantly with the peak
      height of the delta 2.0-2.1 resonance complex in our study. AGP may be partly
      responsible for the resonance complex but other N-acetylated glycoproteins and/or
      glycolipids also contribute. After deproteinization of the cyst fluid, N-acetyl-L
      aspartic acid (NAA) was found to contribute significantly to the signal in this
      spectral region in three of the 12 samples. GC-MS independently confirmed the
      presence of NAA in high concentration in the three samples, which all derived
      from benign serous tumors. We conclude that both NAA and N-acetyl groups from
      glycoproteins and/or glycolipids may contribute to the delta 2.0-2.1 ppm
      resonance complex in ovarian cyst fluid. This spectral region seems to contain
      resonances from biomarkers that provide relevant clinical information on the type
      of ovarian tumor.

PMID- 19593760
TI  - Assessing manganese efflux using SEA0400 and cardiac T1-mapping manganese
      enhanced MRI in a murine model.
AB  - The sodium-calcium exchanger (NCX) is one of the transporters contributing to the
      control of intracellular calcium (Ca(2+)) concentration by normally mediating net
      Ca(2+) efflux. However, the reverse mode of the NCX can cause intracellular
      Ca(2+) concentration overload, which exacerbates the myocardial tissue injury
      resulting from ischemia. Although the NCX inhibitor SEA0400 has been shown to
      therapeutically reduce myocardial injury, no in vivo technique exists to monitor
      intracellular Ca(2+) fluctuations produced by this drug. Cardiac manganese
      enhanced MRI (MEMRI) may indirectly assess Ca(2+) efflux by estimating changes in
      manganese (Mn(2+)) content in vivo, since Mn(2+) has been suggested as a
      surrogate marker for Ca(2+). This study used the MEMRI technique to examine the
      temporal features of cardiac Mn(2+) efflux by implementing a T(1)-mapping method
      and inhibiting the NCX with SEA0400. The change in (1)H(2)O longitudinal
      relaxation rate, Delta R(1), in the left ventricular free wall, was calculated at
      different time points following infusion of 190 nmol/g manganese chloride
      (MnCl(2)) in healthy adult male mice. The results showed 50% MEMRI signal
      attenuation at 3.4 +/- 0.6 h post-MnCl(2) infusion without drug intervention.
      Furthermore, treatment with 50 +/- 0.2 mg/kg of SEA0400 significantly reduced the
      rate of decrease in Delta R(1). At 4.9-5.9 h post-MnCl(2) infusion, the average
      Delta R(1) values for the two groups treated with SEA0400 were 2.46 +/- 0.29 and
      1.72 +/- 0.24 s(-1) for 50 and 20 mg/kg doses, respectively, as compared to the
      value of 1.27 +/- 0.28 s(-1) for the control group. When this in vivo data were
      compared to ex vivo absolute manganese content data, the MEMRI T(1)-mapping
      technique was shown to effectively quantify Mn(2+) efflux rates in the
      myocardium. Therefore, combining an NCX inhibitor with MEMRI may be a useful
      technique for assessing Mn(2+) transport mechanisms and rates in vivo, which may
      reflect changes in Ca(2+) transport.

PMID- 19593762
TI  - Profiling human gut bacterial metabolism and its kinetics using [U-13C]glucose
      and NMR.
AB  - This study introduces a stable-isotope metabolic approach employing [U
      (13)C]glucose that, as a novelty, allows selective profiling of the human
      intestinal microbial metabolic products of carbohydrate food components, as well
      as the measurement of the kinetics of their formation pathways, in a single
      experiment. A well-established, validated in vitro model of human intestinal
      fermentation was inoculated with standardized gastrointestinal microbiota from
      volunteers. After culture stabilization, [U-(13)C]glucose was added as an
      isotopically labeled metabolic precursor. System lumen and dialysate samples were
      taken at regular intervals. Metabolite concentrations and isotopic labeling were
      determined by NMR, GC, and enzymatic methods. The main microbial metabolites were
      lactate, acetate, butyrate, formate, ethanol, and glycerol. They together
      accounted for a (13)C recovery rate as high as 91.2%. Using an NMR chemical shift
      prediction approach, several minor products that showed (13)C incorporation were
      identified as organic acids, amino acids, and various alcohols. Using computer
      modeling of the (12)C contents and (13)C labeling kinetics, the metabolic fluxes
      in the gut microbial pathways for synthesis of lactate, formate, acetate, and
      butyrate were determined separately for glucose and unlabeled background
      substrates. This novel approach enables the study of the modulation of human
      intestinal function by single nutrients, providing a new rational basis for
      achieving control of the short-chain fatty acids profile by manipulating
      substrate and microbiota composition in a purposeful manner.

PMID- 19593763
TI  - The president's role in advancing civic engagement: The Widener-Chester
      Partnership.
AB  - Efforts by metropolitan universities to engage in meaningful and democratic
      partnerships with community organizations require much time, effort, and
      considerable resources from the university and its various constituents. Widener
      University is located in a distressed urban environment. This study, presented
      from the perspective of the university's president, highlights the challenges
      associated with engaging in such work and provides insight into possible future
      directions for advancing an institution-wide civic engagement agenda. It outlines
      in detail the initiatives created between Widener and the Chester, Pennsylvania,
      school district over six years and explains how after many failures, the
      university came to the conclusion that its best chance for success would be to
      develop a separately chartered university partnership school. The account
      forcefully underscores that the costs associated with civic engagement are worth
      the investment in spite of the number of setbacks and frustrations inherent in
      this type of work.

PMID- 19593764
TI  - Diffraction imaging of spheres and melanoma cells with a microscope objective.
AB  - Diffraction imaging of polystyrene spheres and B16F10 mouse melanoma cells
      embedded in gel has been investigated with a microscope objective. The
      diffraction images acquired with the objective from a sphere have been shown to
      be comparable to the Mie theory based projection images of the scattered light if
      the objective is translated to defocused positions towards the sphere. Using a
      confocal imaging based method to reconstruct and analyze the 3D structure, we
      demonstrated that genetic modifications in these cells can induce morphological
      changes and the modified cells can be used as an experimental model for study of
      the correlation between 3D morphology features and diffraction image data.

PMID- 19593765
TI  - Mechanical computation in neurons.
AB  - Growth cones are the main motile structures located at the tip of neurites and
      are composed of a lamellipodium from which thin filopodia emerge. In this
      article, we analyzed the kinetics and dynamics of growth cones with the aim to
      understand two major issues: first, the strategy used by filopodia and
      lamellipodia during their exploration and navigation; second, what kind of
      mechanical problems neurons need to solve during their operation. In the
      developing nervous system and in the adult brain, neurons constantly need to
      solve mechanical problems. Growth cones must decide how to explore the
      environment and in which direction to grow; they also need to establish the
      appropriate contacts, to avoid obstacles and to determine how much force to
      exert. Here, we show that in sparse cultures, filopodia grow and retract
      following statistical patterns, nearly optimal for an efficient exploration of
      the environment. In a dense culture, filopodia exploration is still present
      although significantly reduced. Analysis on 1271, 6432, and 185 pairs of
      filopodia of DRG, PC12 and Hippocampal neurons respectively showed that the
      correlation coefficient |rho| of the growth of more than 50% of filopodia pairs
      was >0.15. From a computational point of view, filopodia and lamellipodia motion
      can be described by a random process in which errors are corrected by efficient
      feedback loops. This article argues that neurons not only process sensory
      signals, but also solve mechanical problems throughout their entire lifespan,
      from the early stages of embryogenesis to adulthood.

PMID- 19593766
TI  - Thermal behaviour and biological activity against Aedes aegypti (Diptera:
      Culicidae) of permethrin and pyriproxyfen in a smoke-generating formulation.
AB  - BACKGROUND: The most common ways to control dengue vector Aedes aegypti (L.) are
      larval source reduction in domestic habitats and ground application of small
      quantities of aerosol insecticide (ultralow volume). Nevertheless, these actions
      have been shown repeatedly to be ineffective in controlling Ae. aegypti
      populations. RESULTS: The efficacy of a new smoke-generating formulation
      containing pyriproxyfen and permethrin was evaluated in the laboratory. Smoke
      generating tablets containing each insecticide individually or combined were
      prepared, and the recovery of the insecticides from the smoke was determined.
      Recovery values of over 90% were obtained for pyriproxyfen, and around 50% for
      permethrin. The biological efficacy of pyriproxyfen released in the smoke was
      evaluated in the laboratory, on late third-instar or early fourth-instar Ae.
      aegypti larvae, using different concentrations of pyriproxyfen and exposure
      times. Adult emergence inhibition (EI) values of 100% were obtained at 30 min,
      and a dose-dependent effect was observed at 5 min. The effect of pyriproxyfen
      released in the smoke was due to direct contact with the larvicide in the water
      rather than by inhalation of the fumes. The efficacy of permethrin released in
      the fumes was also evaluated as knockdown effect (KT(50)) on adults for a tablet
      containing permethrin alone or permethrin plus pyriproxyfen. There was no
      significant difference in KT(50) values obtained for permethrin (KT(50) = 19.9
      min) and permethrin plus pyriproxyfen (KT(50) = 19.4 min). CONCLUSION: The
      excellent laboratory performance of this new formulation on immature stages and
      adults indicates that a smoke-generating tablet containing pyriproxyfen and
      permethrin could be a new tool for controlling mosquitoes.

PMID- 19593767
TI  - Changes in phosphine sorption in wheat after storage at two temperatures.
AB  - BACKGROUND: Wheat can be stored for many months before being fumigated with
      phosphine to kill insects, so a study was undertaken to investigate whether the
      sorptive capacity of wheat changes as it ages. Wheat was stored at 15 or 25
      degrees C and 55% RH for up to 5.5 months, and samples were fumigated at
      intervals to determine sorption. Sealed glass flasks (95% full) were injected
      with 1.5 mg L(-1) of phosphine based on flask volume. Concentrations were
      monitored for 11 days beginning 2 h after injection. Some wheat samples were
      refumigated after a period of ventilation. Several fumigations of wheat were
      conducted to determine the pattern of sorption during the first 24 h. RESULTS:
      Phosphine concentration declined exponentially with time from 2 h after
      injection. Rate of sorption decreased with time spent in storage at either 15 or
      25 degrees C and 55% RH. Rate of sorption tended to be lower when wheat was
      refumigated, but this could be explained by time in storage rather than by
      refumigation per se. The data from the 24 h fumigations did not fit a simple
      exponential decay equation. Instead, there was a rapid decline in the first hour,
      with phosphine concentration falling much more slowly thereafter. CONCLUSIONS:
      The results have implications for phosphine fumigation of insects in stored
      wheat. Both the time wheat has spent in storage and the temperature at which it
      has been stored are factors that must be considered when trying to understand the
      impact of sorption on phosphine concentrations in commercial fumigations.

PMID- 19593768
TI  - T-cell-specific deletion of gp130 renders the highly susceptible IL-10-deficient
      mouse resistant to intestinal nematode infection.
AB  - Gp130 is the common receptor of the IL-6 family of cytokines and is involved in
      many biological processes, including acute phase response, inflammation and
      immune reactions. To investigate the role of gp130 under inflammatory conditions,
      T-cell-specific conditional gp130 mice were first bred to the IL-10-deficient
      background and were then infected with the gastrointestinal nematode Trichuris
      muris. While IL-10(-/-) mice were highly susceptible to T. muris, developed a
      mixed Th1/Th17 response and displayed severe inflammation of the caecum,
      infection of mice with an additional T-cell-specific deletion of gp130 signalling
      completely reversed the phenotype. These mice showed an accelerated worm
      expulsion that was associated with the rapid generation of a strong Th2 immune
      response and a significant increase in Foxp3-expressing Treg. Therefore, gp130
      signalling in T cells regulates a switch between proinflammatory and pathogenic
      Th1/Th17 cells and regulatory Th2/Treg in vivo. Taken together, the data
      demonstrate that gp130 signalling in T cells is a positive regulator of
      inflammatory processes, favouring the Th1/Th17 axis.

PMID- 19593769
TI  - DC within the pregnant mouse uterus influence growth and functional properties of
      uterine NK cells.
AB  - The vascular addressins mucosal addressin cell adhesion molecule-1, P-selectin
      and ICAM-1 permit alpha(4)beta(7)-integrin-expressing DC, especially those of the
      myeloid lineage (CD11c(+)CD11b(+) DC), to access the pregnant mouse uterus.
      Injection of blocking monoclonal antibodies against mucosal addressin cell
      adhesion molecule-1 in P-selectin(-/-) mice or experimental approaches with beta7
      integrin(-/-) or ICAM-1(-/-) mice revealed that limited access or absence of
      CD11c(+)CD11b(+) DC at the maternal/fetal interface negatively affects the
      frequency, size and functional properties of uterine NK (uNK) cells. Adoptive
      transfer of DC obtained from WT mice into beta7-integrin(-/-) mice abrogates
      these effects and emphasizes the importance of DC in uNK cell differentiation.
      Interestingly, those implantation sites lacking CD11c(+)CD11b(+) DC are
      characterized by decreased IL-15 and IL-12 mRNA and/or protein levels. Chronic
      administration of IL-15 in these mice gives rise to uNK cell numbers and size
      comparable to those of WT mice, whereas additional injection of IL-12 positively
      affects the IFN-gamma expression of uNK cells. Real-time RT-PCR and protein
      arrays performed with isolated uterine DC underline the role of DC as a source of
      IL-15 and IL-12 in the pregnant mouse uterus.

PMID- 19593771
TI  - Complete protection against experimental visceral leishmaniasis with complete
      soluble antigen from attenuated Leishmania donovani promastigotes involves Th1
      immunity and down-regulation of IL-10.
AB  - Compared with cutaneous leishmaniasis, vaccination against visceral leishmaniasis
      has received limited attention. Most available drugs are toxic, and relapse after
      cure remains a chronic problem. Growing limitations in available chemotherapeutic
      strategies due to emerging resistant strains and lack of an effective vaccine
      strategy against visceral leishmaniasis deepens the crisis. Complete soluble
      antigen (CSA), from a beta1-4 galactosyltransferase expressing attenuated
      Leishmania donovani parasite, induced protection against subsequent challenge and
      during active infections. CSA immunization was effective against both pentavalent
      antimony sensitive and resistant strains of L. donovani. Majority ( approximately
      85%) of the immunized animals showed sterile protection. Resolution of the
      disease required the presence of T cells, and the recovered animals remained
      immune to re-challenge. Control of the parasites was dependent on type 1 CD4(+)
      helper cells, which evolved in the presence of IL-12 and activated macrophages
      through the production of IFN-gamma. Immunity was adoptively transferable and was
      dependent on both CD4(+) and CD8(+) cells. CSA immunization led to enhanced IFN
      gamma production, while suppressing the IL-10 production. However, CSA
      immunization did not abrogate IL-4 production. Our results accentuate the need to
      establish a favorable cellular immunity while intervening with the development of
      Th2 cells during leishmania infection.

PMID- 19593770
TI  - MMP induced by Gr-1+ cells are crucial for recruitment of Th cells into the
      airways.
AB  - Th2 lymphocytes deliver essential signals for induction of asthmatic airway
      inflammation. We previously found that airway antigen challenge induces
      recruitment of Gr-1(+) neutrophils prior to the recruitment of Th2 cells. We
      examined, therefore, whether Gr-1(+) cells contribute to the development of Th2
      dependent airway inflammation. Systemic depletion of Gr-1(+) cells using the RB6
      8C5 monoclonal antibody reduced Th2 cell recruitment following i.n. antigen
      challenge. The levels of both MMP-9 and the tissue inhibitor of matrix
      metalloproteinases-1 mRNA were up-regulated in the lungs of mice 12 h after i.n.
      antigen challenge. Up-regulation of tissue inhibitor of matrix metalloproteinases
      1 was independent of Gr-1(+) cells, whereas up-regulation of MMP-9 RNA and total
      gelatinolytic activity was dramatically reduced in mice depleted of Gr-1(+)
      cells. At 24 h after challenge, total lung collagenolytic activity was also up
      regulated, in a Gr-1(+) cell-dependent fashion. Systemic inhibition of MMP-8 and
      MMP-9 reduced the airway recruitment of Th cells, resulting in significantly
      reduced eosinophilic inflammation. These data suggest that antigen challenge via
      the airway activates Gr-1(+) cells and consequently MMP to facilitate the
      recruitment of Th cells in the airway inflammatory response.

PMID- 19593772
TI  - Rational optimization of tumor epitopes using in silico analysis-assisted
      substitution of TCR contact residues.
AB  - Altered peptide ligands with increased affinity of the peptide-MHC complex for
      the TCR provide an alternative strategy to natural T-cell epitopes for cancer
      immunotherapy, as they can recruit and stimulate stronger T-cell repertoires.
      However, it remains unclear how alterations of the TCR contact residues improve
      the interaction between the peptide-MHC complex and the TCR molecule. In this
      study, we introduced a molecular simulation strategy to optimize a tumor
      immunodominant epitope NY-ESO-1(157-165) by the substitution of the potential TCR
      contact residues. We correlated molecule simulation with T-cell activation
      capacity assay and detected the effect of modifications of TCR contact residues
      on T-cell recognition. An agonist peptide W5F with substitution at Trp5 with Phe
      was identified and it exhibits a stronger ability to induce a cross-reactive CTL
      response with the WT peptide. Additionally, the W5F-induced CTL could be
      maintained with the WT peptide and possess higher capacity in lysing native NY
      ESO-1-expressing tumor cells. These results provide important insights into the
      enhanced immunogenicity of epitopes through substitution at the TCR contact sites
      and revealed a novel molecular simulation approach for rational therapeutic
      peptide vaccine design.

PMID- 19593774
TI  - Programmatic approaches to assessing and improving animal welfare in zoos and
      aquariums.
AB  - There continues to be intense public, professional, and scientific focus on the
      welfare of animals in zoos and aquariums, but implementing welfare assessment
      tools consistently throughout this community remains challenging. Indirect
      measures can be used to assess "welfare potential"-the potential that animals
      will experience good welfare based on the care that they are provided with. Zoos
      and aquariums focus on welfare potential with their continued commitment to
      develop animal care guidelines (e.g. Animal Care Manuals) that can play a role
      within institutional accreditation or certification. The Association of Zoos and
      Aquariums Animal Welfare Committee has been pursuing approaches to maximize
      welfare potential by developing the concept of an integrated welfare approach or
      framework-an attempt to identify recommended animal care programs (e.g.
      enrichment, nutrition, veterinary care, research, and animal training programs)
      and their programmatic components. Objectively assessing the influence that
      animal care recommendations have on the welfare of individual animals is
      important to determine the efficacy of programmatic approaches. The future of
      welfare assessment within zoos and aquariums will include population-level
      evaluations-tracking emerging trends in health and behavior that come from both
      formal and informal institutional animal reports. Sharing this information, and
      performing meta-analyses of the data using epidemiological approaches, will
      become easier with advances in technology and database management software.
      Identifying welfare "red/green flags" throughout captive populations will provide
      direction for more focused assessments that will ultimately inform the design of
      more effective animal care programs.

PMID- 19593775
TI  - Comparing isotropic and anisotropic smoothing for voxel-based DTI analyses: A
      simulation study.
AB  - Voxel-based analysis (VBA) methods are increasingly being used to compare
      diffusion tensor image (DTI) properties across different populations of subjects.
      Although VBA has many advantages, its results are highly dependent on several
      parameter settings, such as those from the coregistration technique applied to
      align the data, the smoothing kernel, the statistics, and the post-hoc analyses.
      In particular, to increase the signal-to-noise ratio and to mitigate the adverse
      effect of residual image misalignments, DTI data are often smoothed before VBA
      with an isotropic Gaussian kernel with a full width half maximum up to 16 x 16 x
      16 mm(3). However, using isotropic smoothing kernels can significantly partial
      volume or voxel averaging artifacts, adversely affecting the true diffusion
      properties of the underlying fiber tissue. In this work, we compared VBA results
      between the isotropic and an anisotropic Gaussian filtering method using a
      simulated framework. Our results clearly demonstrate an increased sensitivity and
      specificity of detecting a predefined simulated pathology when the anisotropic
      smoothing kernel was used.

PMID- 19593776
TI  - Spatial-temporal dynamics of cortical activity underlying reaching and grasping.
AB  - How humans understand the actions and intentions of others remains poorly
      understood. Here we report the results of a magnetoencephalography (MEG)
      experiment to determine the temporal dynamics and spatial distribution of brain
      regions activated during execution and observation of a reach to grasp motion
      using real world stimuli. We show that although both conditions activate similar
      brain areas, there are distinct differences in the timing, pattern and location
      of activation. Specifically, observation of motion revealed a right hemisphere
      dominance with activation involving a network of regions that include frontal,
      temporal and parietal areas. In addition, the latencies of activation showed a
      task specific pattern. During movement execution, the earliest activation was
      observed in the left premotor and somatosensory regions, followed closely by left
      primary motor and STG at the time of movement onset. During observation, there
      was a shift in the timing of activation with the earliest activity occurring in
      the right temporal region followed by activity in the left motor areas. Activity
      within these areas was also characterized by a shift to a lower frequency in
      comparison with action execution. These results add to the growing body of
      evidence indicating a complex interaction within a distributed network involving
      motor and nonmotor regions during observation of real actions.

PMID- 19593777
TI  - MicroRNA expression profiling of human metastatic cancers identifies cancer gene
      targets.
AB  - Small non-coding microRNAs (miRNAs) contribute to cancer development and
      progression, and are differentially expressed in normal tissues and cancers.
      However, the specific role of miRNAs in the metastatic process is still unknown.
      To seek a specific miRNA expression signature characterizing the metastatic
      phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired
      primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one
      of their related metastatic lymph nodes. We identified a metastatic cancer miRNA
      signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results
      were confirmed by qRT-PCR analysis. Among the miRNAs identified, some have a well
      characterized association with cancer progression, eg miR-10b, miR-21, miR-30a,
      miR-30e, miR-125b, miR-141, miR-200b, miR-200c, and miR-205. To further support
      our data, we performed an immunohistochemical analysis for three well-defined
      miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired
      colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We
      found that the immunohistochemical expression of these targets significantly
      follows the corresponding miRNA deregulation. Our results suggest that specific
      miRNAs may be directly involved in cancer metastasis and that they may represent
      a novel diagnostic tool in the characterization of metastatic cancer gene
      targets.

PMID- 19593778
TI  - Neuroimaging in geriatric psychiatry.

PMID- 19593779
TI  - A multivariate hypothesis testing framework for tissue clustering and
      classification of DTI data.
AB  - The primary aim of this work is to propose and investigate the effectiveness of a
      novel unsupervised tissue clustering and classification algorithm for diffusion
      tensor MRI (DTI) data. The proposed algorithm utilizes information about the
      degree of homogeneity of the distribution of diffusion tensors within voxels. We
      adapt frameworks proposed by Hext and Snedecor, where the null hypothesis of
      diffusion tensors belonging to the same distribution is assessed by an F-test.
      Tissue type is classified according to one of the four possible diffusion models,
      the assignment of which is determined by a parsimonious model selection framework
      based on Schwarz Criterion. Both numerical phantoms and diffusion-weighted
      imaging (DWI) data obtained from excised rat and pig spinal cords are used to
      test and validate these tissue clustering and classification approaches. The
      unsupervised clustering method effectively identifies distinct regions of
      interest (ROIs) in phantoms and real experimental DTI data.

PMID- 19593780
TI  - Neurobiological effects of pulsed magnetic field on diabetes-induced neuropathy.
AB  - In the clinic, although several pharmacological agents or surgical procedures are
      used to treat diabetes and diabetes-induced neuropathic pain, their success has
      been limited. Therefore, development of different alternatives in treatments is
      very important. The purpose of this study was to determine the efficacy of pulsed
      magnetic field (PMF) in improving signs and symptoms of diabetic neuropathy. In
      this study, the effects of PMF treatment were investigated in Streptozotocin
      (STZ)-induced acute and chronic diabetic rats by measuring the thermal latencies,
      mechanical thresholds, whole blood glucose levels and body weights. After STZ
      administration to rats, blood glucose level elevated and body weight decreased.
      Although PMF treatment did not affect changes in body weight, the blood glucose
      levels of PMF-treated diabetic rats exhibited a decrease during the treatments.
      Diabetic animals displayed marked decrease in mechanical thresholds and thermal
      latencies. While treatment of PMF partially restored the mechanical thresholds
      and thermal latency in acute diabetic rats, PMF caused a corrective effect on
      only mechanical threshold of chronic diabetic rats. These results suggested that
      treatment of PMF can potentially ameliorate the painful symptoms of diabetes,
      such as hyperalgesia and allodynia, by partially preventing the hyperglycemia.

PMID- 19593781
TI  - Cytoskeletal forces produced by extremely low-frequency electric fields acting on
      extracellular glycoproteins.
AB  - The physical mechanism by which cells transduce an applied electric field is not
      well understood. This article establishes for the first time a direct,
      quantitative model that links the field to cytoskeletal forces. In a previous
      article, applied electric fields of physiological strength were shown to produce
      significant mechanical torques at the cellular level. In this article, the
      corresponding forces exerted on the cytoskeleton are computed and found to be
      comparable in magnitude to mechanical forces known to produce physiological
      effects. In addition to the electrical force, the viscous drag force exerted by
      the surrounding medium and the restoring force exerted by the neighboring
      structures are considered in the analysis. For an applied electric field of 10
      V/m, the force transmitted to the CD44 receptor of a hyaluronan chain in
      cartilage is about 1 pN at 10 Hz and 7 pN at 1 Hz. For an applied electric field
      of 100 V/m, the force transmitted to the cytoskeleton at one focus of the
      glycocalyx is about 0.5 pN at 10 Hz and 1.3 pN at 1 Hz. Mechanical forces of
      similar magnitude have been observed to produce physiological effects. Hence,
      this electromechanical transduction process is a plausible mechanism for the
      production of physiological effects by such electric fields.

PMID- 19593782
TI  - Micropatterning of covalently attached biotin on poly(lactic acid) film surfaces.
AB  - A two-step approach was used to micropattern covalently attached biotin on the
      surface of poly(lactic acid) (PLA) film. Poly(acrylic acid) (PAA) was
      micropatterned on PLA using photolithography in step 1, followed by carbodiimide
      wet chemistry to covalently attach biotin to acid groups in step 2. The PAA
      micropatterning reaction progression was monitored using attenuated total
      reflectance-Fourier transform infrared (ATR-FT-IR) spectroscopy, water contact
      angle goniometry, and atomic force microscopy (AFM). The PAA-biotin conjugation
      reaction characterization using XPS confirmed the carbodiimide mediated amidation
      reaction. The resultant PLA film was then immersed into a solution of
      fluorescence-conjugated streptavidin and examined under fluorescence microscopy
      to reveal various micropatterns.

PMID- 19593783
TI  - Silicate cross-linked bio-nanocomposite hydrogels from PEO and chitosan.
AB  - The compositions and the multi phase structures of bio-nanocomposite hydrogels
      made from silicate cross-linked PEO and chitosan are related to some of their
      physical and biological properties. The gels are injectable and self-healing
      because the cross-linking is physical and reversible under deformation. The
      presence of chitosan aggregates affects the viscoelastic properties and
      reinforces the hydrogel network. The chitosan adds advantageous properties to the
      hydrogel such as enhanced cell spreading and adhesion. In vitro biocompatibility
      data indicate that NIH 3T3 fibroblasts grow and proliferate on the bio
      nanocomposite hydrogel as well as on hydrogel films.

PMID- 19593784
TI  - Magnetic-fluorescent colloidal nanobeads: preparation and exploitation in cell
      separation experiments.
AB  - Nanostructures displaying fluorescence and magnetic properties at the same time
      are potentially useful for achieving simultaneous bio-separation and bio-sensing
      (e.g., magnetic separation coupled with multiplexing optical detection of
      different tumour cell populations). Spherical nanobeads that display both
      fluorescent and magnetic features are reported; they are fabricated by grafting
      fluorescent oligothiophene molecules to an amphiphilic polymer that is then used
      to enwrap iron oxide nanoparticles, which acts as the magnetic domain. By tuning
      experimental conditions, control over the number of magnetic nanoparticles per
      bead and over the bead diameter (30-400 nm) was achieved. A cell separation
      efficiency of the level required for cell sorting applications is also reported.

PMID- 19593785
TI  - Population analysis of myelosuppression profiles using routine clinical data
      after the ICE (ifosfamide/carboplatin/etoposide) regimen for malignant gliomas.
AB  - We propose a simple and practical modeling approach for analysis of the data for
      myelosuppression after cancer chemotherapy, which can be applied when
      pharmacokinetic data are not available and several anticancer drugs were
      simultaneously administered. The model equation is based on the probability
      density function for the Erlang distribution. The data for cell counts of
      leukocytes (white blood cell, WBC), platelets (PLT), and reticulocytes (RET)
      obtained in routine clinical laboratory tests after the ICE
      (ifosfamide/carboplatin/etoposide) regimen for cancer chemotherapy were
      retrospectively collected from 28 patients, and a population analysis was
      applied. The time course profiles could be well explained by the proposed model.
      The individual values of the time to reach the nadir were obtained by the
      Bayesian method, and their medians (days) were 16.8 for WBC, 12.8 for PLT, and
      8.2 for RET. Such information would be useful to determine the day of visit for
      outpatients especially for additional treatment to prevent side effects such as
      infections. The model is simple and applicable to explain the time course
      profiles for myelosuppression irrespective of cell types, and also practical
      because it requires only the data from routine clinical laboratory tests without
      any additional burden to patients.

PMID- 19593786
TI  - The oxidative metabolism of dimemorfan by human cytochrome P450 enzymes.
AB  - To characterize the human cytochrome P450 (P450) forms involved in dimemorfan
      oxidation (DFO), human liver microsomes, and recombinant P450s were investigated.
      Liquid chromatography-mass spectral analysis suggested that metabolite (M)1 ([M +
      H](+) m/z at 272.200) and M2 ([M + H](+) m/z at 242.190) were d-3-hydroxymethyl-N
      methylmorphinan and d-3-methylmorphinan, respectively. Kinetic analyses of
      microsomal DFO showed that the substrate concentration showing a half-maximal
      velocity (S(50)) of M1 formation was less than that of M2. Microsomal M1 and M2
      formation activities correlated significantly with the CYP2D6 marker,
      dextromethorphan O-demethylation activity. The M2 formation activity was also
      correlated with the CYP3A4 marker, nifedipine oxidation activity. Microsomal M1
      and M2 formation was most sensitive to the inhibition by a CYP2D6 inhibitor,
      paroxetine and a CYP3A4 inhibitor, ketoconazole, respectively. The
      immunoinhibition-defined P450 contributions indicated the participation of
      CYP2C9, CYP2C19, and CYP2D6 in the M1 formation and CYP2B6, CYP2C9, CYP2C19,
      CYP2D6, and CYP3A4 in the M2 formation. Among recombinant P450s, CYP2D6 had the
      highest intrinsic clearance with a K(m) value of 0.02 mM in forming M1. CYP2B6,
      CYP2C9, and CYP2C19 had the K(m) or S(50) values smaller than those (1 mM) of
      CYP2D6 and CYP3A4 in forming M2. These results indicated the participation of
      multiple P450 forms in DFO.

PMID- 19593787
TI  - Dielectric relaxation studies and dissolution behavior of amorphous verapamil
      hydrochloride.
AB  - Verapamil hydrochloride (VH) is a very popular calcium channel blocker.
      Solubility of its crystalline form in the blood reaches only 10-20%. Thus, it
      seems to be very important to improve its bioavailability. In this article, we
      show that the preparation of the amorphous form of VH enhance its dissolution
      rate. In addition we performed dielectric measurements to describe molecular
      dynamics of this active pharmaceutical ingredient (API). Since examined sample is
      typical ionically conducting material, to gain information about structural
      relaxation we employed the dielectric modulus formalism. The temperature
      dependence of the structural relaxation time can be described over the entire
      measured range by a single Vogel-Fulcher-Tamman (VFT) equation. From the VFT fits
      the glass transition temperature was estimated as T(g) = 320.1 K. Below glass
      transition temperature one clearly visible secondary relaxation, with activation
      energy E(a) = 37.8 kJ/mol, was reported. Deviations of experimental data from KWW
      fits on high-frequency flank of alpha-peak indicate the presence of an excess
      wing in tested sample. Based on Kia Ngai's coupling model we identified the
      excess wing as true Johari-Goldstein process.

PMID- 19593788
TI  - Occupational injury disparities in the US hotel industry.
AB  - BACKGROUND: Hotel employees have higher rates of occupational injury and sustain
      more severe injuries than most other service workers. METHOD: OSHA log incidents
      from five unionized hotel companies for a three-year period were analyzed to
      estimate injury rates by job, company, and demographic characteristics. Room
      cleaning work, known to be physically hazardous, was of particular concern.
      RESULTS: A total of 2,865 injuries were reported during 55,327 worker-years of
      observation. The overall injury rate was 5.2 injuries per 100 worker-years. The
      rate was highest for housekeepers (7.9), Hispanic housekeepers (10.6), and about
      double in three companies versus two others. Acute trauma rates were highest in
      kitchen workers (4.0/100) and housekeepers (3.9/100); housekeepers also had the
      highest rate of musculoskeletal disorders (3.2/100). Age, being female or
      Hispanic, job title, and company were all independently associated with injury
      risk. CONCLUSION: Sex- and ethnicity-based disparities in injury rates were only
      partially due to the type of job held and the company in which the work was
      performed.

PMID- 19593789
TI  - Profilin-1 overexpression restores adherens junctions in MDA-MB-231 breast cancer
      cells in R-cadherin-dependent manner.
AB  - Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, is
      downregulated in several different types of adenocarcinoma and elicits tumor
      suppressive effect on breast cancer cell lines. MDA-MB-231 (MDA-231), a breast
      cancer cell line that displays all the characteristics of post-epithelial-to
      mesenchymal transition and does not form cell-cell adhesion, can be reverted to
      an epithelioid phenotype by Pfn1 overexpression. This morphological transition is
      caused by restoration of adherens junctions (AJ) requiring Pfn1's interaction
      with actin. Pfn1 overexpression increases the expression level of R-cadherin (a
      type of cadherin that is endogenously expressed in the parental cell line) and
      restores AJ in MDA-231 cells in R-cadherin-dependent manner. These findings
      highlight important role of Pfn1 in the regulation of epithelial cell-cell
      adhesion.

PMID- 19593790
TI  - VISIONS: the art of science.

PMID- 19593793
TI  - Evaluation of the long-term reconstituting subset of hematopoietic stem cells
      with CD150.
AB  - Blood is a tissue with a high cell turnover rate that is constantly being
      replenished by bone marrow hematopoietic stem cells (HSCs) seeded during fetal
      ontogeny from the liver. Here we show that the long-term (LT) reconstituting
      subset of cKit(+)Thy1.1(lo)Lin(-/lo)Sca1(+)Flk2(-) HSCs is CD150(+). HSCs sourced
      from the fetal liver show LT, multilineage engraftment from E14.5 onward, and the
      CD150 cell surface molecule can readily substitute Thy1.1 as a positive marker of
      LT-HSCs in this tissue. From both fetal liver and adult bone marrow,
      cKit(+)Thy1.1(lo)Lin(-/lo)Sca1(+)Flk2(-) CD150(+) cells exhibit robust LT
      competitive engraftment, self-renewal, multilineage differentiation capacity, and
      an accessible chromatin configuration consistent with high expression of
      erythroid/megakaryoid genes in purified cell subsets. Our data show that, with
      appropriate combinations of cell surface markers, stem cells can be accurately
      isolated to high purity and characterized. This is important for the
      clarification of lineage relationships and the identification of bona fide
      regulators of stem cell self-renewal and differentiation both in normal and
      neoplastic tissues.

PMID- 19593794
TI  - The plant hormone abscisic acid stimulates the proliferation of human hemopoietic
      progenitors through the second messenger cyclic ADP-ribose.
AB  - Abscisic acid (ABA) is a hormone involved in pivotal physiological functions in
      higher plants, such as response to abiotic stress and control of seed dormancy
      and germination. Recently, ABA was demonstrated to be autocrinally produced by
      human granulocytes, beta pancreatic cells, and mesenchymal stem cells (MSC) and
      to stimulate cell-specific functions through a signaling pathway involving the
      second messenger cyclic ADP-ribose (cADPR). Here we show that ABA expands human
      uncommitted hemopoietic progenitors (HP) in vitro, through a cADPR-mediated
      increase of the intracellular calcium concentration ([Ca(2+)](i)). Incubation of
      CD34(+) cells with micromolar ABA also induces transcriptional effects, which
      include NF-kappaB nuclear translocation and transcription of genes encoding for
      several cytokines. Human MSC stimulated with a lymphocyte-conditioned medium
      produce and release ABA at concentrations sufficient to exert growth-stimulatory
      effects on co-cultured CD34(+) cells, as demonstrated by the inhibition of colony
      growth in the presence of an anti-ABA monoclonal antibody. These results provide
      a remarkable example of conservation of a stress hormone and of its second
      messenger from plants to humans and identify ABA as a new hemopoietic growth
      factor involved in the cross-talk between HP and MSC.

PMID- 19593796
TI  - Balancing work and life: a conversation with Mina Bissell. Interviewed by
      Majlinda Lako and Susan Daher.

PMID- 19593795
TI  - Importin 13 serves as a potential marker for corneal epithelial progenitor cells.
AB  - Importin13 (IPO13), the newest member of importin-beta family discovered
      recently, is a unique nucleus-cytoplasm bidirectional transport receptor protein.
      In this study, IPO13 expression in human corneal tissue, limbal epithelial
      primary explant and clonal culture was evaluated by immunostaining and reverse
      transcription polymerase chain reasgon. IPO13 function was evaluated in the
      corneal epithelial culture treated with IPO13 inhibitor, or fetal bovine serum
      (FBS)-containing Dulbecco's modified Eagle's medium (DMEM) medium by colony
      forming efficiency, clone growth capacity, MTT, immunostaining, and Western
      blotting assay. IPO13 protein was expressed mainly in nuclei of limbal epithelial
      basal cells, but not in the other cell layers of limbus and full thickness of
      corneal epithelia. IPO13 was expressed in the majority of epithelial cells in
      early-stage clones and in the margin of late-stage clones. IPO13 was positively
      expressed in mouse TKE2 progenitor cells cultured in keratinocyte serum-free
      defined medium, while it became negative in FBS-containing DMEM, which promoted
      TKE2 cell differentiation. In the presence of IPO13 inhibitor, IPO13 expression
      and the proliferative capacity decreased in human limbal epithelial clones and
      mouse TKE2 cells, which were accompanied with the cell differentiation. In
      conclusion, our findings demonstrate for the first time that IPO13 is uniquely
      expressed by human limbal basal epithelial cells, and plays an important role in
      maintaining the phenotype, high proliferative potential, and less differentiation
      of corneal epithelial progenitor cells, suggesting that IPO13 could serve as a
      novel potential marker for corneal epithelial progenitor cells.

PMID- 19593797
TI  - Efficacy and toxicity of 2 schedules of frontline rituximab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in
      patients with B-cell lymphoma: a randomized phase 2 trial from the French Adult
      Lymphoma Study Group (GELA).
AB  - BACKGROUND: Bortezomib demonstrated promising activity in lymphomas. The authors
      conducted a randomized phase 2 trial of frontline rituximab plus
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with the
      addition of bortezomib in patients with B-cell lymphoma. METHODS: Patients were
      randomized between 2 schedules of bortezomib, Arm A (Days 1, 4, 8, and 11) and
      Arm B (Days 1 and 8), combined with 6 cycles of R-CHOP. For the first patients
      (Step 1), bortezomib was given at a dose of 1 mg/m(2) in Arm A and 1.3 mg/m(2) in
      Arm B. For the next patients (Step 2), doses were increased to 1.3 mg/m(2) and
      1.6 mg/m(2) in Arms A and B, respectively. The primary endpoint was the rate of
      complete response (CR) and unconfirmed CR (CR/CRu) after 6 cycles. RESULTS: Forty
      nine patients were included in the study, and 41 patients (84%) achieved a
      CR/CRu, ie, 18 of 20 patients (90%) in Arm A and 23 of 29 patients (79%) in Arm
      B. There were 6 partial responses and 2 patients with progressive disease.
      Neurologic toxicity occurred in 21 patients (43%) and was grade 2 in 11 patients
      (7 patients in Step 2) and grade 3 in 10 patients (9 patients in Step 2). Other
      grade 3 and 4 toxicities included constipation (n = 1), infections (n = 3), and
      cardiac events (n = 2). Grade 3 and 4 thrombocytopenia and leucopenia occurred in
      14% and 41% of cycles, respectively. CONCLUSIONS: R-CHOP + bortezomib was an
      effective regimen and produced an 84% CR rate. However, the dose-limiting
      neurotoxicity should be kept in mind for further trials with vinca alkaloids or
      other potentially neurotoxic drugs combination therapies.

PMID- 19593800
TI  - Cell motility and the cytoskeleton in transition.

PMID- 19593798
TI  - Genetically transforming human mesenchymal stem cells to sarcomas: changes in
      cellular phenotype and multilineage differentiation potential.
AB  - BACKGROUND: The cell of origin of sarcoma is still unclear. High-grade
      osteosarcomas frequently demonstrate the potential for multipotent
      differentiation and, along with several other lines of evidence, suggest that
      human mesenchymal stem cells (hMSC) might be the cell of origin. METHODS: The
      hMSCs were transformed with retrovirus containing human telomerase reverse
      transcriptase (hTERT), simian virus 40 large t antigen (SV40 TAg), and lentivirus
      containing oncogenic H-Ras serially. The changes of cellular phenotypes and
      multilineage differentiation capacity were observed and compared with the
      standard osteosarcoma cell lines. RESULTS: Two distinct genotypic and phenotypic
      sarcoma cell lines resulted from the same genetic events. The gene expression
      profiles became more complicated and the karyotype became more chaotic during
      hMSCs' tumorigenesis. The motility of transformed hMSC was promoted. hMSC and its
      derivatives could be induced to osteogenic, adipogenic, and chondrogenic
      differentiation except that MSC-TSR4 lost osteogenic differentiation capacity.
      CONCLUSIONS: Multilineage differentiation potential was retained during
      tumorigenesis of hMSCs and distinct sarcoma cell lines could arise with the same
      genetic events, providing good models in better understanding the concept of hMSC
      and in further investigation of the relationship of hMSCs and osteosarcomas.

PMID- 19593801
TI  - Centrosome abnormalities during porcine oocyte aging.
AB  - Centrosomes are critically important for maintaining meiotic spindle integrity in
      the meiosis II (MII) stage where oocytes are arrested in most mammalian species
      before fertilization takes place. In women of advanced ages or during in vitro
      fertilization (IVF) procedures, aneuploidy is frequently seen as a result of
      oocyte aging, which is strongly related to centrosome instability. Abnormal
      distribution of centrosomes and microtubules has been reported in aging human and
      mouse oocytes. This study reports the dynamic changes of centrosomes and the
      microtubule cytoskeleton in porcine oocytes during aging and treatment by
      caffeine to restore spindle integrity in aging oocytes. We tested the effects of
      caffeine on the MII spindle with focus on microtubules and on the centrosome
      proteins gamma-tubulin and NuMA (nuclear mitotic apparatus protein). The results
      revealed that in porcine oocytes aged for 48 hr., centrosomes were absent and
      spindles became abnormal and disorganized; however, caffeine could prevent these
      changes or restore centrosome integrity in the meiotic spindle poles and
      displayed similar MII spindles as those seen in fresh oocytes.

PMID- 19593802
TI  - Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute
      lymphoblastic leukemia in Brazilian children.
AB  - Polymorphic variations of several genes associated with dietary effects and
      exposure to environmental carcinogens may influence susceptibility to leukemia
      development. The objective of the present study was to evaluate the effect of the
      polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1),
      myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been
      implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic
      leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and
      *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with
      childhood ALL and in 364 healthy individuals matched for age and gender from a
      Brazilian population separated by ethnicity (European ancestry and African
      ancestry), using the PCR-RFLP method. The CYP2D6 polymorphism variants were
      associated with an increased risk of ALL. The EPHX1, NQO1, and MPO variant
      genotypes were significantly associated with a reduced risk of childhood ALL. A
      significantly stronger protective effect is observed when the EPHX1, NQO1, and
      MPO variant genotypes are combined suggesting that, CYP2D6 polymorphisms may play
      a role in the susceptibility to pediatric ALL, whereas the EPHX1, NQO1, and MPO
      polymorphisms might have a protective function against leukemogenesis.

PMID- 19593803
TI  - Neutrophil oxidative metabolism in Down syndrome patients with congenital heart
      defects.
AB  - Down syndrome (DS) occurs when an individual has three, rather than two, copies
      of the 21st chromosome. Cytosolic superoxide dismutase (SOD-1) is encoded by a
      gene on chromosome 21 and thus, SOD-1 activity is elevated in patients with DS.
      Forty percent of all cases with DS are associated with congenital heart defects
      (CHD). Although the contribution of SOD1 to disease phenotype is unknown, it is
      considered to be a "molecular marker" of the disease. It was hypothesized herein
      that the presence of CHD may alter the expression of SOD1 and oxidative
      metabolism in patients with DS. This hypothesis was tested via four experimental
      groups as follows: patients with DS without CHD, DS patients with CHD, CHD
      patients without DS and controls. Expression and activity of superoxide dismutase
      (SOD), glutathione peroxidase (GPx), myeloperoxidase (MPO), and catalase (CAT)
      were determined in neutrophils from all experimental groups. Intracellular
      hydrogen peroxide concentration and superoxide release were also evaluated in
      neutrophils. A significant increase was observed in SOD and GPx amount and
      activity in patients with DS with and without CHD. No significant difference was
      found in the amount and activity of MPO and CAT among the different experimental
      groups. Intracellular hydrogen peroxide concentration was similar in all groups,
      whereas a prominent decrease was seen in superoxide release in cases with DS.
      Patients with DS with and without CHD showed no significant differences in any of
      the measured parameters. The data suggest that CHD observed in patients with DS
      does not result from altered redox metabolism associated with the disease.

PMID- 19593804
TI  - Maintenance of bivalve hemocytes for the purpose of delayed DNA strand break
      assessment using the comet assay.
AB  - The lack of appropriate methods for storing intact and viable cells for the
      purpose of delayed DNA strand break analysis has hitherto limited the application
      of the Comet assay to in vitro or in vivo laboratory studies and restricted
      ecologically more relevant field-collected samples to sites in proximity to
      suitable laboratory facilities. In the present article, osmotically corrected
      cell culture media Hanks Balanced Salt Solution (HBSS) and Leibovitz Media (L-15)
      were assessed for their suitability as temporary storage media of blue mussel
      (Mytilus edulis) hemocytes. It was found that hemocytes maintained in either HBSS
      or L-15 could be stored for at least 7 days at 4 degrees C without any
      significant deterioration in cell viability (Trypan blue) or increase in DNA
      strand breaks, expressed as % tail DNA. This approach allows the acquisition and
      examination of samples from organisms exposed in situ at previously unsuitable
      remote sites, thereby greatly increasing the potential ecological relevance of
      Comet assay-derived genotoxicity data.

PMID- 19593805
TI  - Examining the relationship between resilience and posttraumatic growth.
AB  - To extend the literature the present study aims to examine the interrelationships
      between resilience (defined by a lack of posttraumatic stress disorder following
      trauma) and posttraumatic growth. Two studies were conducted of Israeli: (a)
      adolescents exposed to terror (N = 2908), and (b) citizens and army personnel
      following the second Lebanon War (N = 588). Across studies the results showed
      that high levels of resilience were associated with the lowest posttraumatic
      growth scores. The results imply that although growth and resilience are both
      salutogenic constructs they are inversely related. The theoretical and clinical
      implications of these findings are discussed.

PMID- 19593806
TI  - PTSD symptoms, satisfaction with life, and prejudicial attitudes toward the
      adversary among Israeli civilians exposed to ongoing missile attacks.
AB  - Few studies have examined the consequences of exposure to ongoing missile attacks
      in civilian populations. The authors examine the relationships between such
      exposure, and posttraumatic stress disorder (PTSD), satisfaction with life, and
      prejudicial attitudes toward the adversary. By using a stratified probability
      sampling, 160 adults, exposed to repeated missile attacks in southern Israel,
      were compared to 181 adults from areas outside the range of these attacks.
      Exposed participants reported more PTSD symptoms and less satisfaction with life,
      as compared to unexposed participants. The associations between PTSD and
      satisfaction with life and between PTSD and prejudicial attitudes were
      significantly stronger among the exposed participants, as compared to those who
      were not exposed to the attacks. Theoretical and clinical implications of the
      findings are discussed.

PMID- 19593807
TI  - Psychological consequences of forced evacuation on children: risk and protective
      factors.
AB  - Children's psychological distress and symptoms after forced evacuation from the
      Gaza Strip in Israel were studied. Fifty families living in temporary residences
      2 weeks postevacuation were assessed for general political and evacuation life
      events exposure as risk factors and family support and hardiness as protective
      factors. The hypothesis predicting a positive correlation between forced
      evacuation events and political life events and symptom levels was confirmed.
      Perceived family support served as a significant predictor of symptomatology, but
      not family hardiness, substantiating parents' role in aiding children's coping.

PMID- 19593808
TI  - Issue editors' notes. Special issue: universities in partnership: strategies for
      education, youth development, and community renewal.

PMID- 19593810
TI  - University-school-community partnerships for youth development and democratic
      renewal.
AB  - Democratic partnerships of universities, schools, and an array of neighborhood
      and community organizations are the most promising means of improving the lives
      of our nation's young people. Over the past two decades, many colleges and
      universities have been experiencing a renaissance in engagement activities.
      Universities, once ivory towers, have increasingly come to recognize that their
      destinies are inextricably linked with their communities. Authentic democratic
      partnerships have three characteristics: they are devised to achieve democratic
      purposes, the collective work is advanced through inclusive and democratic
      processes, and the product these partnerships produce benefits all participants
      and results in a strengthening of the democratic practices within the community.

PMID- 19593811
TI  - The connection: schooling, youth development, and community building-The Futures
      Academy case.
AB  - Universities, because of their vast human and fiscal resources, can play the
      central role in assisting in the development of school-centered community
      development programs that make youth development their top priority. The Futures
      Academy, a K-8 public school in the Fruit Belt, an inner-city neighborhood in
      Buffalo, New York, offers a useful model of community development in partnership
      with the Center for Urban Studies at the State University of New York at Buffalo.
      The goal of the project is to create opportunities for students to apply the
      knowledge and skills they learn in the classroom to the goal of working with
      others to make the neighborhood a better place to live. The efforts seek to
      realize in practice the Dewey dictum that individuals learn best when they have
      "a real motive behind and a real outcome ahead."

PMID- 19593812
TI  - George Washington Community High School: analysis of a partnership network.
AB  - After five years with no public schools in their community, residents and
      neighborhood organizations of the Near Westside of Indianapolis advocated for the
      opening of George Washington Community High School (GWCHS). As a neighborhood in
      close proximity to the campus of Indiana University-Purdue University
      Indianapolis, the Near Westside and campus worked together to address this issue
      and improve the educational success of youth. In fall 2000, GWCHS opened as a
      community school and now thrives as a national model, due in part to its network
      of community relationships. This account analyzes the development of the school
      by focusing on the relationships among the university, the high school, community
      organizations, and the residents of the Near Westside and highlights the unique
      partnership between the campus and school by defining the relational qualities
      and describing the network created to make sustainable changes with the high
      school.

PMID- 19593813
TI  - Diabetes-related changes in hearing.
AB  - OBJECTIVES/HYPOTHESIS: Determine the effects on hearing of diabetes mellitus (DM)
      severity. STUDY DESIGN: We conducted a cross-sectional study among Veterans to
      investigate the relationship of diabetes severity and hearing in randomly
      selected subjects with (165) and without (137) DM and who had no more than a
      moderate hearing loss. METHODS: Subjects were classified by three age tertiles
      (<50, 50-56, and 57+ years). Diabetes severity was classified as insulin
      dependent (IDDM), noninsulin-dependent (NIDDM), or no DM. Other DM measures
      included concurrent serum glucose, serum HbA(1c), duration of disease, and
      several measures of DM-related complications. Pure-tone thresholds were measured
      in both ears of each subject at frequencies from 250 Hz through 14,000 Hz.
      Outcome measures were adjusted for age and frequency and analyzed for differences
      between subject groups using analysis of variance. Contrasts of the mean NIDDM
      and IDDM thresholds at each frequency to the DM group, and controlled for the
      effects of frequency, age, and interactions were modeled. RESULTS: There was
      greater hearing loss in younger tertile DM subjects compared to those without DM.
      Significant hearing differences were at all frequencies for NIDDM subjects, but
      for IDDM subjects, differences were at 1,000 Hz and below, and 10,000 Hz and
      above. Over age 50 years, there were significant associations between hearing at
      low frequencies and IDDM only. Self-report of prior noise exposure did not
      explain observed differences. CONCLUSIONS: Diabetes is associated with an
      increased risk of hearing loss, and this difference is manifest particularly in
      adults <50 years old.

PMID- 19593814
TI  - The L49F mutation in alpha erythroid spectrin induces local disorder in the
      tetramer association region: Fluorescence and molecular dynamics studies of free
      and bound alpha spectrin.
AB  - The bundling of the N-terminal, partial domain helix (Helix C') of human
      erythroid alpha-spectrin (alphaI) with the C-terminal, partial domain helices
      (Helices A' and B') of erythroid beta-spectrin (betaI) to give a spectrin pseudo
      structural domain (triple helical bundle A'B'C') has long been recognized as a
      crucial step in forming functional spectrin tetramers in erythrocytes. We have
      used apparent polarity and Stern-Volmer quenching constants of Helix C' of alphaI
      bound to Helices A' and B' of betaI, along with previous NMR and EPR results, to
      propose a model for the triple helical bundle. This model was used as the input
      structure for molecular dynamics simulations for both wild type (WT) and alphaI
      mutant L49F. The simulation output structures show a stable helical bundle for
      WT, but not for L49F. In WT, four critical interactions were identified: two
      hydrophobic clusters and two salt bridges. However, in L49F, the region
      downstream of Helix C' was unable to assume a helical conformation and one
      critical hydrophobic cluster was disrupted. Other molecular interactions critical
      to the WT helical bundle were also weakened in L49F, possibly leading to the
      lower tetramer levels observed in patients with this mutation-induced blood
      disorder.

PMID- 19593817
TI  - The Agatston Urban Nutrition Initiative: working to reverse the obesity epidemic
      through academically based community service.
AB  - The Agatston Urban Nutrition Initiative (AUNI) presents a fruitful partnership
      between faculty and students at a premier research university and members of the
      surrounding community aimed at addressing the problem of childhood obesity. AUNI
      uses a problem-solving approach to learning by focusing course activities,
      including service-learning, on understanding and mitigating the obesity culture.

PMID- 19593816
TI  - C-terminal deletion of leucine-rich repeats from YopM reveals a heterogeneous
      distribution of stability in a cooperatively folded protein.
AB  - Terminal deletions of units from alpha-helical repeat proteins have provided
      insight into the physical origins of their cooperativity. To test if the same
      principles governing cooperativity apply to beta-sheet-containing repeat
      proteins, we have created a series of C-terminal deletion constructs from a large
      leucine-rich repeat (LRR) protein, YopM. We have examined the structure and
      stability of the resulting deletion constructs by a combination of solution
      spectroscopy, equilibrium denaturation studies, and limited proteolysis.
      Surprisingly, a high degree of nonuniformity was found in the stability
      distribution of YopM. Unlike previously studied repeat proteins, we identified
      several key LRR that on deletion disrupt nearby structure, at distances as far
      away as up to three repeats, in YopM. This partial unfolding model is supported
      by limited proteolysis studies and by point substitution in repeats predicted to
      be disordered as a result of deletion of adjacent repeats. We show that key
      internal- and terminal-caps must be present to maintain the structural integrity
      in adjacent regions (roughly four LRRs long) of decreased stability. The finding
      that full-length YopM maintains a high level of cooperativity in equilibrium
      unfolding underscores the importance of interfacial interactions in stabilizing
      locally unstable regions of structure.

PMID- 19593815
TI  - Detailed insights from microarray and crystallographic studies into carbohydrate
      recognition by microneme protein 1 (MIC1) of Toxoplasma gondii.
AB  - The intracellular protozoan Toxoplasma gondii is among the most widespread
      parasites. The broad host cell range of the parasite can be explained by
      carbohydrate microarray screening analyses that have demonstrated the ability of
      the T. gondii adhesive protein, TgMIC1, to bind to a wide spectrum of sialyl
      oligosaccharide ligands. Here, we investigate by further microarray analyses in a
      dose-response format the differential binding of TgMIC1 to 2-3- and 2-6-linked
      sialyl carbohydrates. Interestingly, two novel synthetic fluorinated analogs of
      3'SiaLacNAc(1-4) and 3'SiaLacNAc(1-3) were identified as highly potent ligands.
      To understand the structural basis of the carbohydrate binding specificity of
      TgMIC1, we have determined the crystal structures of TgMIC1 micronemal adhesive
      repeat (MAR)-region (TgMIC1-MARR) in complex with five sialyl-N-acetyllactosamine
      analogs. These crystal structures have revealed a specific, water-mediated
      hydrogen bond network that accounts for the preferential binding of TgMIC1-MARR
      to arrayed 2-3-linked sialyl oligosaccharides and the high potency of the
      fluorinated analogs. Furthermore, we provide strong evidence for the first
      observation of a C--F...H--O hydrogen bond within a lectin-carbohydrate complex.
      Finally, detailed comparison with other oligosaccharide-protein complexes in the
      Protein Data Bank (PDB) reveals a new family of sialic-acid binding sites from
      lectins in parasites, bacteria, and viruses.

PMID- 19593818
TI  - Dayton's neighborhood school centers.
AB  - When Dayton Public Schools committed to return to neighborhood K-8 schools, the
      community organized to refocus many youth programs in schools and neighborhoods.
      This article describes the planning and implementation of Dayton's Neighborhood
      School Centers. Special emphasis is placed on the role of the University of
      Dayton, especially the Fitz Center for Leadership in Community. The Fitz Center
      plays a pivotal role in implementing this highly collaborative effort, including
      project leadership; community organizing; coaching of five site coordinators at
      neighborhood school sites; and faculty-mentored student interns to assist with
      programming for student success, family support, health and team sports, and
      extensive service-learning coordination. The Dayton Foundation, Dayton Public
      Schools, City of Dayton, Montgomery County, and sixteen foundation and corporate
      supporters are partners with the Fitz Center in a bold initiative to reconnect
      five Dayton public elementary schools to their neighborhoods, after more than
      thirty years of court-ordered busing, and create full-service, year-round
      opportunities for neighborhood families and youth at these new schools. More than
      forty programs have been started at each site, all emphasizing youth and
      community assets.

PMID- 19593820
TI  - An apoptosis biomarker for prediction of nonalcoholic steatohepatitis.

PMID- 19593819
TI  - Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene
      expression via adenosine monophosphate-activated protein kinase-dependent
      induction of orphan nuclear receptor small heterodimer partner.
AB  - Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic
      system and serves as a possible predictor for hepatic metabolic syndromes.
      Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha)
      agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor
      small heterodimer partner (SHP) plays a key role in transcriptional repression of
      crucial genes involved in various metabolic pathways. In this study, we show that
      fenofibrate increased SHP gene expression in cultured liver cells and in the
      normal and diabetic mouse liver by activating the adenosine monophosphate
      activated protein kinase (AMPK) signaling pathway in a PPARalpha-independent
      manner. Administration of transforming growth factor beta (TGF-beta) or a
      methionine-deficient and choline-deficient (MCD) diet to induce the progressive
      fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by
      fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic
      decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other
      fibrotic marker genes. No reversal was observed in SHP null mice treated with
      fenofibrate. Treatment with another PPARalpha agonist, WY14643, showed
      contrasting effects on these marker gene expressions in wild-type and SHP null
      mice, demonstrating the specificity of fenofibrate in activating AMPK signaling.
      Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression
      depending on the transcription factors inhibited by SHP. CONCLUSION: By
      demonstrating that a PPARalpha-independent fenofibrate-AMPK-SHP regulatory
      cascade can play a key role in PAI-1 gene down-regulation and reversal of
      fibrosis, our study suggests that various AMPK activators regulating SHP might
      provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes.

PMID- 19593821
TI  - In vivo measurement of somatodendritic release of dopamine in the ventral
      tegmental area.
AB  - The ventral tegmental area (VTA), the locus of mesolimbic dopamine cell bodies,
      contains dopamine. Experiments in brain slices have demonstrated that VTA
      dopamine can be released by local electrical stimulation. Measurements with both
      push-pull cannula and microdialysis in intact animals have also obtained evidence
      for releasable dopamine. Here we demonstrate that dopamine release in the VTA can
      be evoked by remote stimulations of the medial forebrain bundle (MFB) in the
      anesthetized rat. In initial experiments, the MFB was electrically stimulated
      while a carbon-fiber electrode was lowered to the VTA, with recording by fast
      scan cyclic voltammetry. While release was not observed with the carbon fiber 4-6
      mm below dura, a voltammetric response was observed at 6-8 mm below dura, but the
      voltammogram was poorly defined. At lower depths, in the VTA, dopamine release
      was evoked. Immunohistochemistry experiments with antibodies for tyrosine
      hydroxylase (TH) confirmed that dopamine processes were primarily found below 8
      mm. Similarly, tissue content determined by liquid chromatography revealed
      serotonin but not dopamine dorsal to 8 mm with both dopamine and serotonin at
      lower depths. Evaluation of the VTA signal by pharmacological means showed that
      it increased with inhibitors of dopamine uptake, but release was not altered by
      D2 agents. Dopamine release in the VTA was frequency dependent and could be
      exhausted by stimulations longer than 5 s. Thus, VTA dopamine release can be
      evoked in vivo by remote stimulations and it resembles release in terminal
      regions, possessing a similar uptake mechanism and a finite releasable storage
      pool.

PMID- 19593823
TI  - Evaluation of N-benzyl-N-[11C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H
      purin-9-yl)acetamide ([11C]DAC) as a novel translocator protein (18 kDa)
      radioligand in kainic acid-lesioned rat.
AB  - The aim of this study was to evaluate N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2
      phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a new translocator
      protein (18 kDa) [TSPO, formerly known as the peripheral-type benzodiazepine
      receptor (PBR)] positron emission tomography (PET) ligand in normal mice and
      unilateral kainic acid (KA)-lesioned rats. DAC is a derivative of AC-5216, which
      is a potent and selective PET ligand for the clinical investigation of TSPO. The
      binding affinity and selectivity of DAC for TSPO were similar to those of AC
      5216, and DAC was less lipophilic than AC-5216. The distribution pattern of
      [11C]DAC was in agreement with TSPO distribution in rodents. No radioactive
      metabolite of [11C]DAC was found in the mouse brain, although it was metabolized
      rapidly in mouse plasma. Using small-animal PET, we examined the in vivo binding
      of [11C]DAC for TSPO in KA-lesioned rats. [11C]DAC and [11C]AC-5216 exhibited
      similar brain uptake in the lesioned and nonlesioned striatum, respectively. The
      binding of [11C]DAC to TSPO was increased significantly in the lesioned striatum,
      and [(11)C]DAC showed good contrast between the lesioned and nonlesioned striatum
      (the maximum ratio was about threefold). In displacement experiments, the uptake
      of [11C]DAC in the lesioned striatum was eventually blocked using an excess of
      either unlabeled DAC or PK11195 injected. [11C]DAC had high in vivo specific
      binding to TSPO in the injured rat brain. Therefore, [11C]DAC is a useful PET
      ligand for TSPO imaging, and its specific binding to TSPO is suitable as a new
      biomarker for brain injury.

PMID- 19593822
TI  - Deficits in substance P mRNA levels in the CeA are inversely associated with
      alcohol-motivated responding.
AB  - In the present study, in vitro and in vivo studies were conducted to determine
      the relationship between innate substance P (SP) levels and alcohol-motivated
      behavior in alcohol-preferring (P) and nonpreferring (NP) rat lines. In
      Experiment 1, in situ hybridization and quantitative autoradiography were used to
      detect and measure SP mRNA levels in discrete brain loci of the P and NP rats.
      The results indicated significantly lower SP mRNA levels in the central nucleus
      of the amygdala (CeA) of P compared with those of NP rats. Experiment 2 evaluated
      the effects of SP, microinfused into the CeA, on alcohol (10%, v/v) and sucrose
      (2%, w/v) motivated responding in the P rat. The results revealed that, when
      infused into the CeA (1-8 microg), SP reduced alcohol responding by 48-85% of
      control levels, with no effects on sucrose responding. Neuroanatomical control
      infusions (1-8 microg) into the caudate putamen (CPu) also failed to
      significantly alter alcohol- or sucrose-motivated behaviors. Given the selective
      reductions on alcohol (compared to sucrose) responding by direct intracranial
      infusion of SP, the data suggest that deficits in SP signaling within the CeA (an
      anxiety regulating locus) are inversely associated with alcohol-motivated
      behaviors. Activation of SP receptors in the CeA may reduce anxiety-like behavior
      in the P rat and contribute to reductions on alcohol responding. The SP system
      may be a suitable target for the development of drugs to reduce alcohol-drinking
      behavior in humans.

PMID- 19593824
TI  - Endocannabinoid modulation of amphetamine sensitization is disrupted in a rodent
      model of lesion-induced dopamine dysregulation.
AB  - We tested the hypothesis that increased dopaminergic sensitivity induced by
      olfactory bulbectomy is mediated by dysregulation of endocannabinoid signaling.
      Bilateral olfactory bulbectomy induces behavioral and neurobiological
      symptomatology related to increased dopaminergic sensitivity. Rats underwent
      olfactory bulbectomy or sham operations and were assessed 2 weeks later in two
      tests of hyperdopaminergic responsivity: locomotor response to novelty and
      locomotor sensitization to amphetamine. Amphetamine (1 mg/kg i.p.) was
      administered to rats once daily for 8 consecutive days to induce locomotor
      sensitization. URB597, an inhibitor of the anandamide hydrolyzing enzyme fatty
      acid amide hydrolase (FAAH), was administered daily (0.3 mg/kg i.p.) to sham and
      olfactory bulbectomized (OBX) rats to investigate the impact of FAAH inhibition
      on locomotor sensitization to amphetamine. Pharmacological specificity was
      evaluated with the CB(1) antagonist/inverse agonist rimonabant (1 mg/kg i.p). OBX
      rats exhibited heightened locomotor activity in response to exposure either to a
      novel open field or to amphetamine administration relative to sham-operated rats.
      URB597 produced a CB(1)-mediated attenuation of amphetamine-induced locomotor
      sensitization in sham-operated rats. By contrast, URB597 failed to inhibit
      amphetamine sensitization in OBX rats. The present results demonstrate that
      enhanced endocannabinoid transmission attenuates development of amphetamine
      sensitization in intact animals but not in animals with OBX-induced dopaminergic
      dysfunction. Our data collectively suggest that the endocannabinoid system is
      compromised in olfactory bulbectomized rats.

PMID- 19593825
TI  - Periodic mesoporous organosilica materials: self-assembly of carbamothioic acid
      bridged organosilane precursors.
AB  - A new series of carbamothioic acid-containing periodic mesoporous organosilica
      (PMO) materials has been synthesized by a direct cocondensation method, in which
      an organosilica precursor N,S-bis[3-(triethoxysilyl)propyl]carbamothioic acid
      (MI) is treated with tetraethyl orthosilicate (TEOS), and the nonionic surfactant
      Pluronic 123 (P123) is used as a template under acidic conditions in the presence
      of inorganic additives. Moreover, the synthesis of the PMO material consisting of
      the MI precursor without TEOS has been realized. These novel PMO materials have
      large surface areas, well-ordered mesoporous structures, hollow fiberlike
      morphologies, and thick walls. They are also structurally well-ordered with a
      high organosilica precursor content, and the carbamothioic acid groups are
      thermally stable up to 250 degrees C. Furthermore, the organosilica materials
      exhibit hydrothermal stability in basic solution.

PMID- 19593826
TI  - Rational modification of the hierarchy of intermolecular interactions in
      molecular crystal structures by using tunable halogen bonds.
AB  - A family of 16 isomolecular salts (3-XpyH)(2)[MX'(4)] (3-XpyH = 3-halopyridinium;
      M = Co, Zn; X = (F), Cl, Br, (I); X' = Cl, Br, I) each containing rigid organic
      cations and tetrahedral halometallate anions has been prepared and characterized
      by X-ray single crystal and/or powder diffraction. Their crystal structures
      reflect the competition and cooperation between non-covalent interactions: N
      H...X'-M hydrogen bonds, C-X...X'-M halogen bonds and pi-pi stacking. The latter
      are essentially unchanged in strength across the series, but both halogen bonds
      and hydrogen bonds are modified in strength upon changing the halogens involved.
      Changing the organic halogen (X) from F to I strengthens the C-X...X'-M halogen
      bonds, whereas an analogous change of the inorganic halogen (X') weakens both
      halogen bonds and N-H...X'-M hydrogen bonds. By so tuning the strength of the
      putative halogen bonds from repulsive to weak to moderately strong attractive
      interactions, the hierarchy of the interactions has been modified rationally
      leading to systematic changes in crystal packing. Three classes of crystal
      structure are obtained. In type A (C-F...X'-M) halogen bonds are absent. The
      structure is directed by N-H...X'-M hydrogen bonds and pi-stacking interactions.
      In type B structures, involving small organic halogens (X) and large inorganic
      halogens (X'), long (weak) C-X...X'-M interactions are observed with type I
      halogen-halogen interaction geometries (C-X...X' approximately = X...X'-M
      approximately = 155 degrees), but hydrogen bonds still dominate. Thus, minor but
      quite significant perturbations from the type A structure arise. In type C,
      involving larger organic halogens (X) and smaller inorganic halogens (X'),
      stronger halogen bonds are formed with a type II halogen-halogen interaction
      geometry (C-X...X' approximately = 180 degrees; X...X'-M approximately = 110
      degrees) that is electrostatically attractive. The halogen bonds play a major
      role alongside hydrogen bonds in directing the type C structures, which as a
      result are quite different from type A and B.

PMID- 19593827
TI  - Ionic liquid crystals formed by self-assembly around an anionic anthracene core.
AB  - We have designed and synthesised a series of modular, mesogenic complexes based
      on anthracene-2,6-disulfonate and trialkoxybenzyl-functionalised imidazolium
      cations. Each complex contains a central, rigid, dianionic anthracene core and
      two flexible monocations bearing paraffin chains anchored on imidazolium rings.
      Anthracene-2,6-disulfonate can be crystallised with various simple alkylammonium
      ions and, in the case of +N(CH3)2(C16H33)2, a crystal structure determination has
      shown that the long paraffinic chains are intercalated between the anthracene
      moieties. The dianion forms columnar mesophases with trialkoxybenzylimidazolium
      cations, as identified by polarising optical microscopy and X-ray scattering
      measurements. Differential scanning calorimetry studies confirmed mesomorphic
      behaviour from room temperature to about 200 degrees C for alkyl chains
      containing 8, 12 and 16 carbon atoms. The strong luminescence of anthracene is
      maintained in the mesophase and fluorescence measurements confirmed the presence
      of J aggregates in all cases. The new functional materials described herein
      provide an easy access to stable and luminescent mesomorphic materials engineered
      by an ionic self-assembly process.

PMID- 19593828
TI  - Re4Si7, first in a new MoSi2-based family of 14-electron phases.

PMID- 19593829
TI  - Cycloaddition reactions of kinetically stabilized 9-silaanthrancene with
      polycyclic aromatic hydrocarbons.

PMID- 19593830
TI  - Self-assembled monolayers of mono-tetrathiafulvalene calix[4]pyrroles and their
      electrochemical sensing of chloride.

PMID- 19593831
TI  - Selectivity control in Lewis acid catalyzed regiodivergent tandem cationic
      cyclization/ring expansion terminated by pinacol rearrangement.

PMID- 19593832
TI  - Network topology of a hybrid organic zinc phosphate with bimodal porosity and
      hydrogen adsorption.

PMID- 19593833
TI  - Regulating copper-binding affinity with photoisomerizable azobenzene ligand by
      construction of a self-assembled monolayer.

PMID- 19593834
TI  - Evolution of propargyl ethers into allylgold cations in the cyclization of
      enynes.

PMID- 19593835
TI  - Ruthenium-catalyzed regioselective direct alkylation of arenes with unactivated
      alkyl halides through C-H bond cleavage.

PMID- 19593836
TI  - Size-selective sorption of small organic molecules in one-dimensional channels of
      an ionic crystalline organic-inorganic hybrid compound stabilized by pi-pi
      interactions.

PMID- 19593837
TI  - Formation and characterization of the iridium tetroxide molecule with iridium in
      the oxidation state +VIII.

PMID- 19593838
TI  - Electrical switching of 1,2-bis(2-methyl-5-phenyl-3-thienyl)
      perfluorocyclopentene in the solid state.

PMID- 19593839
TI  - Light-driven thermoelectric conversion based on a carbon nanotube-ionic liquid
      gel composite.

PMID- 19593840
TI  - Chest X-ray quiz. Dextrocardia and increased markings at the right base due to
      bronchiectasis.

PMID- 19593841
TI  - Proceedings of the 11th International Workshop on Multiple Endocrine Neoplasias
      (MEN2008). September 25-27, 2008. Delphi, Greece.

PMID- 19593844
TI  - Proceedings of the Fifth International Conference for Rickettsiae and Rickettsial
      Diseases. Marseilles, France. May 18-20, 2008.

PMID- 19593845
TI  - Extra-nuclear steroid receptors: integration with multiple signaling pathways.
      Proceedings of the FASEB Summer Research Meeting. July 27-August 1, 2008.
      Carefree, Arizona, USA.

PMID- 19593843
TI  - Sensation seeking as a predictor of treatment compliance and smoking cessation
      treatment outcomes in heavy social drinkers.
AB  - The personality trait of sensation seeking has been positively associated with
      risk of smoking initiation and level of tobacco use. However, its role in smoking
      cessation is much less established. This study examined the association between
      sensation seeking and smoking cessation among 236 heavy social drinkers
      participating in a clinical trial testing the efficacy of incorporating brief
      alcohol intervention into smoking cessation treatment. As hypothesized, higher
      sensation seeking predicted reduced odds of abstinence from smoking as well as
      greater alcohol use over 26 weeks of follow-up. Sensation seeking also
      significantly interacted with age, having a protective influence on smoking
      outcomes among the youngest participants and an increasingly negative effect on
      smoking outcomes with greater age. Compliance with nicotine replacement therapy
      and use of smoking cessation strategies (e.g., planning for high risk situations,
      thinking about the benefits of quitting, avoiding smoking situations) were
      negatively associated with sensation seeking and accounted for most of the main
      effect of sensation seeking on smoking outcomes. Findings suggest (a) that
      smokers high in sensation seeking may require a specific emphasis on treatment
      compliance and behavioral rehearsal of cessation strategies, and (b) that the
      significance of sensation seeking for smoking cessation may change with
      increasing age.

PMID- 19593842
TI  - The maturation of incentive processing and cognitive control.
AB  - Understanding how immaturities in the reward system affect decision-making can
      inform us on adolescent vulnerabilities to risk-taking, which is a primary
      contributor to mortality and substance abuse in this age group. In this paper, we
      review the literature characterizing the neurodevelopment of reward and cognitive
      control and propose a model for adolescent reward processing. While the
      functional neuroanatomy of the mature reward system has been well-delineated,
      adolescent reward processing is just beginning to be understood. Results indicate
      that adolescents relative to adults demonstrate decreased anticipatory processing
      and assessment of risk, but an increased consummatory response. Such differences
      could result in suboptimal representations of reward valence and value and bias
      adolescent decision-making. These functional differences in reward processing
      occur in parallel with on-going structural and pharmacological maturation in the
      adolescent brain. In addition to limitations in incentive processing, basic
      cognitive control abilities, including working memory and inhibitory control,
      continue to mature during adolescence. Consequently, adolescents may be limited,
      relative to adults, in their abilities to inhibit impulsive behaviors and
      reliably hold 'on-line' comparisons of potential rewards/punishments during
      decision-making.

PMID- 19593846
TI  - Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48
      overproduction by regulating inflammatory, insulin, and lipoprotein pathways in
      enterocytes.
AB  - We have previously reported that the obesity-associated proinflammatory cytokine,
      TNF-alpha, stimulates the overproduction of intestinal apolipoprotein (apo) B48
      containing lipoproteins. In the current study, we have evaluated whether a water
      soluble cinnamon extract [CE (Cinnulin PF)] attenuates the dyslipidemia induced
      by TNF-alpha in Triton WR-1339 treated hamsters, and whether CE inhibits the
      oversecrection of apoB48-induced by TNF-alpha in enterocytes in a 35S labeling
      study. In vivo, oral treatment of Cinnulin PF (50 mg per kg BW), inhibited the
      postprandial overproduction of apoB48-containing lipoproteins and serum
      triglyceride levels. In ex vivo 35S labeling studies, CE (10 and 20 microg/ml)
      inhibited the oversecretion of apoB48 induced by TNF-alpha treated enterocytes
      into the media. To determine the molecular mechanisms, TNF-alpha treated primary
      enterocytes isolated from chow-fed hamsters, were incubated with CE (10
      microg/ml), and the expression of the inflammatory factor genes, IL1-beta, IL-6,
      and TNF-alpha, insulin signaling pathway genes, insulin receptor (IR), IRS1,
      IRS2, phosphatidylinositol 3-kinase (PI3-K), Akt1 and phosphatase and tensin
      homology (PTEN), as well as the key regulators of lipid metabolism, cluster of
      differentiation (CD)36, microsomal triglyceride transfer protein (MTTP), and
      sterol regulatory element binding protein (SREBP)-1c were evaluated. Quantitative
      real-time PCR assays showed that CE treatment decreased the mRNA expression of IL
      1beta, IL-6 and TNF-alpha, improved the mRNA expression of IR, IRS1, IRS2, PI3K
      and Akt1, inhibited CD36, MTTP, and PTEN, and enhanced the impaired SREBP-1c
      expression in TNF-alpha treated enterocytes. These data suggest that a water
      extract of cinnamon reverses TNF-alpha-induced overproduction of intestinal
      apoB48 by regulating gene expression involving inflammatory, insulin, and
      lipoprotein signaling pathways. In conclusion, Cinulin PF improves inflammation
      related intestinal dyslipidemia.

PMID- 19593848
TI  - Proceedings of the 101st Annual Meeting of the Swiss Society of Ophthalmology.
      September 10-13, 2008. Interlaken, Switzerland.

PMID- 19593847
TI  - [Effectiveness of interventions for undernourished older inpatients in the
      hospital setting].

PMID- 19593849
TI  - Mesophyll conductance to CO2: mechanisms, modelling, and ecological implications.
      Proceedings of a workshop. September 2009. Sa Coma, Mallorca, Spain.

PMID- 19593850
TI  - Prostate-cancer screening.

PMID- 19593851
TI  - Prostate-cancer screening.

PMID- 19593852
TI  - Prostate-cancer screening.

PMID- 19593853
TI  - Prostate-cancer screening.

PMID- 19593854
TI  - Prostate-cancer screening.

PMID- 19593855
TI  - Esomeprazole for asthma.

PMID- 19593856
TI  - Esomeprazole for asthma.

PMID- 19593857
TI  - Long-acting beta-agonists in asthma.

PMID- 19593858
TI  - Patient information page from the Hormone Foundation. High blood calcium
      (Hypercalcemia).

PMID- 19593859
TI  - [Pseudomembranous colitis].

PMID- 19593861
TI  - Parathyroid incidentalomas detected on routine ultrasound-directed fine-needle
      aspiration biopsy in patients referred for thyroid nodules and the role of
      parathyroid hormone analysis in the samples.
AB  - BACKGROUND: The widespread use of high-resolution ultrasound (US) has allowed the
      detection of not only nonpalpable thyroid nodules but also parathyroid
      incidentalomas in the general population. We sought to determine the prevalence
      of parathyroid incidentalomas in a large group of patients referred for US-guided
      fineneedle aspiration biopsy (FNAB) of suspected thyroid nodules and to
      investigate the role of additional parathyroid hormone (PTH) analysis in the
      washouts of FNAB of suspicious papathyroid nodules in these patients. METHODS:
      Between June 2006 and December 2007, US-guided FNAB (US-FNAB) was performed in
      6469 patients. Among them, 112 patients (1.7%) underwent additional PTH analysis
      in FNAB washouts (FNA-PTH) due to suspected parathyroid lesions. A retrospective
      review of clinical, radiologic, cytologic, and pathologic records was conducted.
      We evaluated the prevalence of parathyroid adenomas that were detected on thyroid
      US incidentally as well as the results of FNAB and FNA-PTH in parathyroid
      adenomas that were confirmed histopathologically. RESULTS: Parathyroid
      incidentalomas were identified in 14 patients based on pathology and 10 patients
      based on elevated FNA-PTH. The occurrence of parathyroid incidentalomas was 0.4%
      (24=6496) on thyroid US. For the detection of the incidentalomas, the positive
      predictive value (PPV) of thyroid US was 21.4% (24=112). When an inadequate
      specimen was considered as being of nonparathyroid origin, the sensitivity of
      FNAB was 41.7%, specificity was 97.7%, accuracy was 85.7%, PPV was 83.3%, and
      negative predictive value (NPV) was 86% in 112 patients. The diagnostic
      performance of FNA-PTH in 18 operated nodules showed a sensitivity of 92.9%,
      specificity of 100%, accuracy of 94.4%, PPV of 100%, and NPV of 80%. Four
      patients noticed symptoms related to hyperparathyroidism after FNA-PTH analysis.
      CONCLUSIONS: The prevalence of parathyroid incidentaloma was 0.4% (24=6496) in a
      large series of patients referred for suspected thyroid nodules. The use of FNA
      PTH combined with FNAB can help clinicians accurately diagnose parathyroid
      incidentalomas at the time of US-guided FNAB.

PMID- 19593860
TI  - Racial and ethnic differences in willingness to participate in psychiatric
      genetic research.
AB  - OBJECTIVE: The National Institute of Mental Health's effort to rectify the
      underrepresentation of American Blacks in the genetic studies of psychiatric
      disorders has met with mixed success. This study was designed to understand some
      of the barriers to recruitment. METHODS: Men and women, who were of Black, White
      or Hispanic race/ethnicity, aged 18-79 years (N= 353), were recruited from
      clinical and community settings in New York City. Participants responded to a
      survey that was designed to measure willingness to participate and attitudes
      toward genetic research. Principal components analyses generated eight factors
      including perceived benefits, concerns about, and drawbacks of genetic research,
      and beliefs about genetic or environmental contributions to psychopathology.
      Analysis of variance assessed within-ethnic group differences on factor scores,
      as they related to willingness to participate in genetic research. RESULTS:
      Ethnic groups did not differ significantly in stated willingness to participate
      in genetic research; more than 70% in each group were willing to participate.
      Among Blacks and Hispanics, mistrust and wariness, and stigma were significantly
      increased in those unwilling to participate; for Whites, perceived benefit to
      society and perceived importance for knowledge/education were associated with
      willingness to participate. For Blacks and Hispanics, youth (aged 18-29 years)
      and college education reduced, but did not eliminate the association between
      wariness and mistrust and willingness to participate. CONCLUSION: Findings
      suggest that recruitment efforts aimed at increasing the representation of Blacks
      should be aware of the barriers among those who are less educated, and involve
      interactive community collaborations, to fully address the mistrust in this
      population.

PMID- 19593862
TI  - [Digestive disturbances in Parkinson disease].

PMID- 19593863
TI  - [Insanity in the young: diagnostic course].

PMID- 19593864
TI  - [Quality of life in multiple sclerosis: theoretical and practical aspects].

PMID- 19593865
TI  - Ethics column. Working through an ethical dilemma.

PMID- 19593867
TI  - Response to research.

PMID- 19593868
TI  - Medical reserve core.

PMID- 19593869
TI  - African traditional medicine.

PMID- 19593870
TI  - Arbitrary actions.

PMID- 19593871
TI  - The tokoloshe homunculus.

PMID- 19593872
TI  - Medical aid double standards.

PMID- 19593873
TI  - Proceedings of the Third International Conference of Quantitative Genetics.
      August 18-24, 2007. Hangzhou, China.

PMID- 19593874
TI  - [Apathy and the syndrome of dopaminergic dysregulation in Parkinson disease: does
      a continuum exist?].

PMID- 19593875
TI  - [Parkinson disease: genetics and neuronal death].

PMID- 19593876
TI  - [Axonal problems in demyelinating pathologies: role of inflammation and
      demyelinization].

PMID- 19593878
TI  - Reproductive Bioengineering 2008. Proceedings of a meeting. April 2008. Wenns im
      Pitztal, Austria.

PMID- 19593877
TI  - [Thrombolytic therapy in ischemic strokes].

PMID- 19593879
TI  - Anatomical or functional imaging in endocrine  hypertension: competition or
      synergy?

PMID- 19593880
TI  - [In which cases does molecular biology allow a diagnosis in neuromuscular
      pathology?].

PMID- 19593881
TI  - [Behavioral problems in Alzheimer disease: current and future treatments].

PMID- 19593883
TI  - [Freezing of gait: clinical problems and therapy].

PMID- 19593882
TI  - [Physiopathology of cerebral ischemia: what is the contribution of future
      treatments?].

PMID- 19593884
TI  - [Biological markers in Alzheimer disease: what are the chances for less slow
      diagnosis?].

PMID- 19593885
TI  - [Pragmatic approach to treatments in multiple sclerosis].

PMID- 19593886
TI  - 'Scheduled' dosing of lornoxicam provides analgesia superior to that provided by
      'on request' dosing following craniotomy.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the efficacy of
      'scheduled' analgesia with analgesia 'on request in patients after craniotomy.
      PATIENTS AND METHODS: We performed a prospective randomized study comparing
      'scheduled' analgesia with analgesia 'on request' on 126 patients aged 16-70
      years undergoing craniotomy for a variety of reasons. Patients were randomized to
      one of two groups; group 1 (68 patients) received lornoxicam 'on request', and
      group 2 (58 patients) received 8 mg of lornoxicam preoperatively, immediately
      after intubation, then 8 mg again 6-8 h after the first injection and 8 mg
      repeated every 8 h for 48 h postoperatively. Subgroup analysis was performed for
      patients with supratentorial and infratentorial craniotomy. We measured pain
      scores (visual analogue scale), mean blood pressure and heart rate at 6, 18, 30,
      42 and 54 h after surgery and compared differences in these parameters between
      groups and amongst subgroups. RESULTS AND DISCUSSION: Group 1 visual analogue
      pain scale scores were significantly higher than those in group 2 (P < 0.05).
      Group 1 patients with infratentorial craniotomy showed higher pain scores than
      supratentorial craniotomy patients (P < 0.05). No significant differences were
      observed in mean blood pressure between groups and subgroups (P > 0.05). We found
      no correlation between visual analogue scale scores, mean blood pressure and
      heart rate (P > 0.05). CONCLUSION: 'Scheduled' analgesia with lornoxicam was more
      effective for treating post-craniotomy pain than 'on request' analgesia with
      lornoxicam.

PMID- 19593887
TI  - Postoperative analgesia for arthroscopic shoulder surgery: a prospective
      randomized controlled study of intraarticular, subacromial injection,
      interscalenic brachial plexus block and intraarticular plus subacromial injection
      efficacy.
AB  - BACKGROUND AND OBJECTIVES: The aim of the present study was to compare the new
      combination of intraarticular + subacromial injection, with intraarticular,
      subacromial injection and interscalenic brachial plexus block as postoperative
      analgesia in shoulder arthroscopy. METHODS: One hundred and twenty patients
      scheduled for shoulder arthroscopy were enrolled and randomly assigned to one of
      five groups: intraarticular, subacromial, interscalenic brachial plexus block
      (IBPB), intraarticular + subacromial (intraarticular + subacromial) injection or
      a control group. All patients received standardized general anaesthesia and all
      the injections were given with the same dose and volume of local anaesthetic. The
      number of boluses (fentanyl 1 microg kg(-1) delivered by a patient-controlled
      analgesia pump applied at the end of the surgery and the visual analogue pain
      score (VAPS) at 0, 2, 4, 6, 12, 18 and 24 h after the intervention were recorded.
      A patient satisfaction score was also assessed at 24 h. RESULTS: Mean bolus
      consumption, compared with control group, was significantly less in all groups (P
      < 0.01). Intraarticular + subacromial group utilized fewer boluses compared with
      subacromial group and significantly lower boluses than intraarticular group (P <
      0.01), but IBPB group utilized significantly fewer boluses than intraarticular +
      subacromial group. Patients in IBPB, intraarticular + subacromial and subacromial
      groups showed VAPSs that were significantly better than that of the control group
      at all time points (P < 0.01). The VAPS in intraarticular + subacromial group was
      statistically comparable with those in IBPB and subacromial groups at each time
      interval. IBPB and intraarticular + subacromial groups showed comparable patient
      satisfaction scores. CONCLUSION: These results confirm the analgesic efficacy of
      IBPB for shoulder surgery. Nonetheless, the combination of intraarticular and
      subacromial infiltration, studied for the first time, appears to be a clinically
      valid alternative with no clinical meaningful adverse effects.

PMID- 19593888
TI  - Supplement: Advances in pediatric plastic surgery.

PMID- 19593889
TI  - Interleukin-18: an independent predictor of cardiovascular  events in patients
      with acute coronary syndrome  after 6 months of follow-up.
AB  - BACKGROUND: Interleukin-18 (IL-18), a proinflammatory cytokine, has been
      associated with atherogenesis and plaque rupture in acute coronary syndrome
      (ACS). Recent studies suggest that IL-18 may have a long-term prognostic value.
      The aim of this study was to evaluate the relationship between IL-18 levels and
      major adverse cardiovascular events within 6 months of follow-up in post-ACS
      patients. METHODS: One hundred and twelve consecutive patients admitted to a
      university hospital with ACS were included in the study. IL-18 and C-reactive
      protein were measured within the first 24 h of admission. Six months after
      hospital discharge, the incidence of major adverse cardiovascular events
      (cardiovascular death, new episode of ACS, and need for unplanned
      revascularization) was assessed. RESULTS: Mean age of patients was 64 +/- 11
      years, and 58 (52%) were male. During the 6 months of follow-up, 33 patients
      (31.4%) experienced major adverse cardiovascular events. Median IL-18 serum
      levels were higher among patients who had events than among those who did not:
      271.7 pg/ml (interquartile range: 172.9-389.6) and 139.7 pg/ml (interquartile
      range: 99.9-265.7), respectively (P < 0.01). In the Cox multivariate analysis,
      after adjustment for clinical risk factors and serum troponin, elevated levels of
      IL-18 were associated with higher incidence of events (hazard ratio: 2.5; 95%
      confidence interval: 1.14-5.52; P = 0.023). In this population, C-reactive
      protein was of borderline significance for events. CONCLUSION: Serum IL-18 levels
      in ACS patients were independent predictors of long-term cardiovascular events.
      These findings support the association between inflammation and prognosis of ACS
      patients, as well as the clinical impact of this biomarker.

PMID- 19593890
TI  - Preconditioning effects of adenosine in patients with severe  coronary artery
      disease but preserved coronary flow reserve.
AB  - BACKGROUND: Adenosine plays a key role in different protective and adaptive
      responses to ischemia and has been suggested to induce ischemic preconditioning.
      AIM: To investigate whether a low-dose adenosine infusion reduces the ischemic
      burden induced by pharmacological stress without affecting the coronary flow
      reserve (CFR). MATERIALS AND METHODS: Myocardial ischemia was induced by
      dobutamine stress test and quantified by tissue Doppler echocardiography in 11
      patients with advanced coronary artery disease. CFR was quantified during high
      dose adenosine infusion by contrast echocardiography. Before the dobutamine
      stress test and contrast echocardiography, intravenous low-dose adenosine or
      placebo was infused over 15 min according to a randomized, double-blind, cross
      over protocol. Echocardiographic left ventricular (LV) apical images and flow
      pattern of left anterior descending coronary artery (LAD) were obtained at
      baseline, during adenosine/placebo infusion, maximal, and recovery
      phases.Furthermore, the LV walls were categorized as ischemic or nonischemic
      according to a predefined ischemic threshold of at least 25% increment in peak
      systolic velocity (PSV)from baseline to maximal stress. CFR was measured as the
      ratio of peak/baseline of maximal diastolic velocity in the distal LAD. RESULTS:
      PSV increased both during placebo and adenosine infusions from baseline to
      maximal stress. However, in the ischemic walls, the PSV increased only during
      adenosine infusion, whereas no differences were observed in the nonischemic
      walls. There were no differences in blood pressure, heart rate, or regional CFR
      during placebo or adenosine infusion. CONCLUSION: Low-dose adenosine infusion
      improves regional LV systolic function in the ischemic walls, without any effect
      on CFR, suggesting that the observed improvement may be because of ischemic
      preconditioning.

PMID- 19593891
TI  - Unusual cervical spine injury by fishing harpoon.
AB  - Modern fishing and hunting weapons are powerful and capable of causing severe
      tissue damage, similarly to gunshot wounds. The principles of management after
      fish harpoon penetrating injuries include primary basic life support, followed by
      trajectory surgical removal and wound care. Clinicians should know about the
      structures and the mechanisms of fishing harpoons and how to manage these
      injuries to avoid fatal complications. Lesions to the neck produced by underwater
      fishing harpoon, are extremely rare. Herein we describe a case of an unusual
      injury of cervical spine by fishing harpoon, and we discuss the appropriate
      management.

PMID- 19593892
TI  - Some English illustrated medical books.

PMID- 19593893
TI  - GPRC5A: A potential tumor suppressor and oncogene.

PMID- 19593894
TI  - Corrigenda and addenda to Diel's Galenica.

PMID- 19593895
TI  - Epidemiological investigation of prognosis.

PMID- 19593896
TI  - Why museums matter: a tale of pinworms (Oxyuroidea: Heteroxynematidae) among
      pikas (Ochotona princeps and O. collaris) in the American west.
AB  - Permanent and well-supported museum or natural history collections provide a
      solid foundation for the process of systematics research through creation of an
      empirical record which validates our understanding of the biosphere. We explore
      the role of museums in ongoing studies of the complex helminth fauna
      characteristic of pikas (Ochotona spp.) in the American west. These studies
      address the taxonomy for pinworms of the Labiostomatinae and the problems
      associated with the absence of adequate type series and vouchers and with
      misidentifications in original descriptions. We demonstrate that the types for
      Labiostomum (Labiostomum) coloradensis are identical to some specimens in the
      syntype series representing L. (Eugenuris) utahensis, although the published
      descriptions are in disagreement. Both are identical to L. (Eugenuris)
      talkeetnaeuris and, as a consequence, are reduced as junior synonyms. Only 2
      species of large pinworms, namely L. (Labiostomum) rauschi and L. (Eugenuris)
      talkeetnaeuris, are widely distributed in Ochotona collaris and O. princeps.
      Although this serves to clarify the taxonomy for species in these genera, prior
      records remain confused, as representative voucher specimens from all major
      surveys in North America were never submitted to museum collections. We strongly
      suggest that type and voucher series should not be held in private or personal
      collections, where such are eventually lost, discarded, or destroyed through
      neglect due to inattention and the absence of curation. The potential to
      accumulate meaningful baselines for assessment of environmental change is
      jeopardized if materials from survey and inventory are not routinely submitted to
      museum collections. The capacity of museum repositories, as a focus for
      systematics, ecology, and evolutionary studies and for the development of
      resources for biodiversity informatics, continues to be undervalued and poorly
      utilized by a cadre of scientists who are dependant on accurate and definitive
      information that transcends specific disciplines.

PMID- 19593897
TI  - Free hype vs. free clinics.

PMID- 19593898
TI  - Pediatric pharmacology in the first year of life.
AB  - PURPOSE OF REVIEW: Toxicity concerns and awareness during anesthesia issues
      continue to concern pediatric anesthesiologists. Most developmental
      pharmacokinetic, pharmacodynamic and pharmacogenomic changes occur within the
      first year of life. Understanding these early changes can improve drug use in
      this cohort. RECENT FINDINGS: Growth and development are two major aspects of
      children not readily apparent in adults. Clearance in the pediatric population
      should be investigated using models that describe size, maturation and organ
      function influences. Glucuronide conjugation (hepatic phase II process) mirrors
      glomerular filtration maturation over the first year of life. Phase 1 processes
      appear more rapid, and differences attributable to single nuclear polymorphisms
      may be obvious by the end of the 4-week neonatal period in term
      infants.Pharmacodynamic differences in infancy remain poorly defined, and
      neonatal pharmacokinetic-pharmacodynamic analyses that might elucidate such
      differences are few, partly because of a paucity of effective pharmacodynamic
      measures. SUMMARY: Mechanistic models create a framework for the study of
      pharmacokinetic changes in infancy. Understanding these changes allows a target
      concentration approach to therapy and potential for reduced toxicity. The target
      concentration may be undefined because of a paucity of effect measures.

PMID- 19593899
TI  - Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing
      elective surgery.
AB  - BACKGROUND AND OBJECTIVES: Inhaled anaesthetics have been studied regarding their
      genotoxic and mutagenic potential in vivo. Propofol differs from volatile
      anaesthetics because it does not show mutagenic effects and it has been reported
      to be an antioxidant. However, there are no studies with propofol and
      genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is
      not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in
      patients undergoing propofol anaesthesia. METHODS: ASA physical status I patients
      scheduled for elective surgery, lasting at least 90 min, were enrolled in this
      study. Initially, the estimated plasma concentration of propofol was targeted at
      4 microg ml(-1) and then maintained at 2-4 microg ml(-1) until the end of
      surgery. Haemodynamic data were determined at baseline (before premedication) and
      in conjunction with target-controlled infusion of propofol: after tracheal
      intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the
      surgery. Venous blood samples were collected at baseline, after tracheal
      intubation, at the end of the surgery and on the postoperative first day for
      evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA
      levels. RESULTS: Haemodynamic data did not differ among times. No statistically
      significant differences were observed for the levels of DNA damage in WBCs, nor
      in plasma MDA, among the four times. CONCLUSION: Propofol does not induce DNA
      damage in WBCs and does not alter MDA in plasma of patients.

PMID- 19593900
TI  - Predictors of occult bacteremia in young febrile children in the era of
      heptavalent pneumococcal conjugated vaccine.
AB  - BACKGROUND: Changes in the prevalence of pneumococcal occult bacteremia (PnOB)
      because of pneumococcal conjugated vaccine (PCV-7) may have altered the
      predictive value of the complete blood count (CBC) for selected patients at risk
      of having occult bacteremia (OB). OBJECTIVE: To analyze the rate of OB in infants
      with high fever without source related to pneumococcal vaccination status and to
      study the yield of the CBC to identify children with OB in the era of PCV-7.
      METHODS: Retrospective review of 1586 children of age 3-36 months admitted to a
      Pediatric Emergency Department with a CBC and a blood culture performed as part
      of their evaluation for fever. Patients with altered urinalysis were excluded.
      RESULTS: Blood culture was positive in 15 (0.9%; pneumococcus 10, 0.6%). Of the
      1586 children, 1040 (65.6%) showed less than 15,000 leukocytes/mm3 (2 PnOB,
      0.19%). Of the 546 children with more than 15,000 leukocytes/mm3, eight had a
      PnOB (positive predictive value =1.46%, negative predictive value= 99.8%). Of the
      1586 children, 1177 (74.2%) showed absolute neutrophil count less than 10,000/mm3
      (3 PnOB, 0.25%). Of those 409 with more than 10,000 neutrophil/mm3, seven had a
      PnOB (positive predictive value= 1.71%, negative predictive value= 99.7%). Among
      the 429 children with at least two doses of PCV-7, one (0.23%) had a PnOB (vs.
      nine of 1090 - 0.82% - with no dose or one dose of PCV-7). CONCLUSION: In the era
      of PCV-7, rate of PnOB is related to the pneumococcal vaccination status. The
      yield of the CBC is lower than in the prevaccinal era. Decisions based on CBC
      must be reconsidered.

PMID- 19593901
TI  - Need for emergency department observation after  scorpion sting: prospective
      study and review of the  literature in the Middle East.
AB  - OBJECTIVE: To question the existing practice to observe the victims of scorpion
      sting in the emergency department at least for 6 h. METHODS: Prospective study of
      all adult patients presenting to emergency department after scorpion sting during
      3 years, and review of existing literature from Middle East countries.
      CONCLUSION: Serious toxicity after scorpion sting in Israel and some of
      neighboring countries is rare, and always presents within 1 h from the sting.
      Thus, prolonged observation can be reserved for a high-risk population and
      patients with serious toxicity on admission.

PMID- 19593902
TI  - Restrictive cardiomyopathy.

PMID- 19593903
TI  - The impact of Asiatic cholera on Pittsburgh, Wheeling, and Charleston.

PMID- 19593904
TI  - A note on Ante-bellum southern nationalism and medical practice.

PMID- 19593905
TI  - An account of the epidemic fevers that prevailed in the city of New York from
      1791 to 1822.

PMID- 19593906
TI  - Austin Flint, M.D. and the north Boston, New York typhoid epidemic of 1843.

PMID- 19593907
TI  - An unnoticed translation of the chapter De elementis from Nemesius' De natura
      hominis.

PMID- 19593908
TI  - A selective list of the colonial manuscripts (1564-1800) in the archives of the
      Department of Health and Welfare, Mexico City.

PMID- 19593909
TI  - Traditional medicine in Communist China: science, Communism and cultural
      nationalism.

PMID- 19593910
TI  - A store mixt, various, universal.

PMID- 19593911
TI  - Brief history of the American Philosophical Society.

PMID- 19593912
TI  - Some medical remedies of the early nineteenth century.

PMID- 19593913
TI  - Impact of epidemic yellow fever on life in Louisiana.

PMID- 19593914
TI  - Yellow fever in New Orleans, 1853: abstractions and realities.

PMID- 19593915
TI  - ECOLOGY AND WILDLIFE: Pharmed Fish.

PMID- 19593917
TI  - Representations of physical plausibility revealed by event-related potentials.
AB  - Maintaining an accurate mental representation of the current environment is
      crucial to detecting change in that environment and ensuring behavioral
      coherence. Past experience with interactions between objects, such as collisions,
      has been shown to influence the perception of object interactions. To assess
      whether mental representations of object interactions derived from experience
      influence the maintenance of a mental model of the current stimulus environment,
      we presented physically plausible and implausible collision events while
      recording brain electrical activity. The parietal P300 response to 'oddball'
      events was found to be modulated by the physical plausibility of the stimuli,
      suggesting that past experience of object interactions can influence working
      memory processes involved in monitoring ongoing changes to the environment.

PMID- 19593916
TI  - Trilostane exerts antidepressive effects among wild-type, but not estrogen
      receptor [beta] knockout mice.
AB  - Women with estrogen receptor (ER) positive breast cancer, who are treated with
      the ER blocker, tamoxifen, have an increased risk of depression. Trilostane, a 3b
      hydroxysteroid dehydrogenase inhibitor, is now being used to treat tamoxifen
      insensitive breast cancer. In-vitro assays show that trilostane may have actions
      through ERb. Results of in-vivo research shows that actions at ERb may underline
      some antidepressant effects of estrogen. We hypothesized that trilostane may
      exert antidepressive effects in the forced swim in part due to actions through
      ERb. Trilostane (25 mg/kg, intraperitoneally), compared with vehicle, had
      significant antidepressant-like effects but only when administered to wild-type,
      not ERb knockout, mice. Thus, actions of trilostane through ERb may underlie some
      of its antidepressant-like effects.

PMID- 19593918
TI  - Yankees versus Yellow Jack in New Orleans, 1862-1866.

PMID- 19593919
TI  - The water supply of Rome.
AB  - The water delivery system developed by the Romans stands as a monument to the
      engineering ability of that city-state's water commissioners. This is an article
      about that system and, in particular, one of its ablest administrators-
      Frontinus.

PMID- 19593920
TI  - Hidden themes in the frontier thesis: an application of psycho-analysis to
      historiography.

PMID- 19593921
TI  - Meat! It is what you do not know that hurts you: why FDA should reevaluate the
      use of carbon monoxide in modified atmospheric meat packaging.

PMID- 19593922
TI  - Why self-regulation does not work: resolving prescription corruption caused by
      excessive gift-giving by pharmaceutical manufacturers.

PMID- 19593923
TI  - [Clinico-pharmacology of glucocorticoids].

PMID- 19593924
TI  - [Children's health and physical activities].

PMID- 19593925
TI  - [Status of the development of tuberculosis-preventing vaccines and possibility of
      their use].

PMID- 19593926
TI  - [Determination of psychosocial factors (1). Psychological characteristics 1.
      Reliability].

PMID- 19593927
TI  - Spatial and temporal patterns of Ambystoma tigrinum virus (ATV) prevalence in
      tiger salamanders Ambystoma tigrinum nebulosum.
AB  - Amphibian ranaviruses have been documented as causes of mass mortality in
      amphibian populations throughout the world. The temporal and spatial dynamics of
      ranavirus infections when epidemics are not apparent remains unclear. To address
      this question, we collected tissue samples from 2003 to 2006 in 4 geographically
      separated tiger salamander Ambystoma tigrinum nebulosum host populations on the
      Kaibab Plateau in northern Arizona. We tested for Ambystoma tigrinum virus (ATV),
      a lethal ranavirus of tiger salamanders, calculated ATV prevalence for each
      sampling date, and examined temporal and spatial patterns by quantifying the
      annual level of ATV synchrony among populations using the intraclass correlation
      coefficient. Salamander populations were commonly infected with ATV. We observed
      no morbidity or mortality in these populations even as ATV prevalence values
      varied from 0 to 57%. Infection prevalence across the landscape was more similar
      within a given year than between years. There was no statistically significant
      spatial pattern in prevalence across the landscape. Our findings highlight the
      need to explore new hypotheses regarding the population level impact of these
      pathogens on amphibian communities.

PMID- 19593928
TI  - Ranavirus in wild edible frogs Pelophylax kl. esculentus in Denmark.
AB  - A survey for the amphibian pathogens ranavirus and Batrachochytrium dendrobatidis
      (Bd) was conducted in Denmark during August and September 2008. The public was
      encouraged via the media to register unusual mortalities in a web-based survey.
      All members of the public that registered cases were interviewed by phone and 10
      cases were examined on suspicion of disease-induced mortality. All samples were
      negative for Bd. Ranavirus was isolated from 2 samples of recently dead frogs
      collected during a mass mortality event in an artificial pond near Slagelse,
      Denmark. The identity of the virus was confirmed by immunofluorescent antibody
      test. Sequencing of the major capsid protein gene showed the isolate had more
      than 97.3% nucleotide homology to 6 other ranaviruses.

PMID- 19593929
TI  - Primary diagnosis and surveillance of white spot syndrome virus in wild and
      farmed crawfish (Procambarus clarkii, P. zonangulus) in Louisiana, USA.
AB  - This is the first report of natural white spot syndrome virus (WSSV) infection in
      wild and large-scale farmed crawfish. In the spring of 2007, 3 crawfish farms
      experienced heavy mortality in ponds populated by Procambarus clarkii and P.
      zonangulus. Histological examination revealed findings consistent with severe
      viral infection characterized by numerous intranuclear inclusions in ectodermal
      and mesodermal tissues. Samples tested by in situ hybridization, injection
      bioassay in Litopenaeus vannamei, and PCR (nested and real time) were all
      positive for WSSV. Samples were sent to the National Veterinary Services
      Laboratory in Ames, Iowa, USA, where WSSV was verified. Subsequently, a multi
      parish survey of 184 sites in Louisiana (including farm and wild basin samples)
      using real-time PCR determined that >60% of sites sampled were positive for WSSV,
      including wild basin samples.

PMID- 19593930
TI  - White spot syndrome virus VP37 interacts with VP28 and VP26.
AB  - White spot syndrome virus (WSSV) is one of the most virulent pathogens affecting
      penaeid shrimp, causing high mortality in infected populations. Interactions
      between virus structural proteins are likely to be important for virus assembly.
      Many steps of the WSSV assembly and maturation pathway remain unclear. In the
      present study, the interaction between VP37 and envelope or nucleocapsid proteins
      was characterized. VP37 was expressed in Escherichia coli and confirmed by
      Western blotting. Pure WSSV virions were subjected to Triton X-100 treatment to
      separate the envelope and nucleocapsid fractions. Overlay assays showed that VP37
      interacted with VP28 and VP26. The interaction of VP37 with VP28 and VP26 was
      confirmed further by His pull-down and matrix-assisted laser desorption
      ionization (MALDI) mass spectrographic assays. The binding assay of VP37 with
      VP28 by ELISA confirmed that the 2 proteins had direct interaction in vivo. This
      discovery will help elucidate the molecular mechanisms of virion morphogenesis.

PMID- 19593931
TI  - Phylogenetic analysis of spring viraemia of carp virus isolates from Austria
      indicates the existence of at least two subgroups within genogroup Id.
AB  - Genetic relationships between 22 spring viraemia of carp virus (SVCV) isolates
      from Austria collected between 1994 and 2007 were determined based on the partial
      nucleotide sequence of the glycoprotein gene (G gene). Phylogenetic analyses
      located all Austrian isolates except one in genogroup Id. One isolate collected
      in 2007 was placed within the SVCV Ia genogroup. More importantly, the study also
      revealed 3 distinct clusters within genogroup Id, designated Id1, Id2 and Id3.
      Existence of subgroups Id2 and Id3 within the genogroup Id was supported by high
      bootstrap values. The genetic clustering could neither be linked to host species
      nor to geographic localization of fish farms. Furthermore, no clear link could be
      established between the pathological lesions and phylogenetic relationship.
      However, time-dependent division of the isolates was observed. Viruses from the
      Id1 cluster were mainly sampled in Austria in the 1990s and up until 2003,
      whereas all viruses from the Id2 subgroup were isolated after 2003.

PMID- 19593932
TI  - Ultrastructural and phylogenetic data of Chloromyxum riorajum sp. nov. (Myxozoa),
      a parasite of the stingray Rioraja agassizii in Southern Brazil.
AB  - We describe a new myxozoan parasite found infecting the gall bladder of the
      cartilaginous fish Rioraja agassizii (Rajidae) from the South Atlantic coast of
      Brazil. Light microscopy, scanning and transmission electron microscopy and
      phylogenetic data were used. Numerous irregular polyspqric plasmodia externally
      covered by numerous microvilli containing different stages of sporogony,
      including free spores, were observed in bile. Ellipsoidal spores, on average
      11.41 microm long, 8.48 microm wide and 7.32 microm thick, were formed by 2 equal
      sized valves, each possessing 3 to 4 (rarely 5) elevated ridges which projected
      from the basal portion of the spore, and joined along a sinuous S-shaped sutural
      line. The basal portion of the valves bore a bundle of 33 to 37 extended tapering
      caudal filaments attached to the basal portion of the last ridge and basal
      portion of the sutural edge of the 2 valves. The caudal filaments, formed of
      material similar to the valves, were attached to the shell wall by a conical
      basis. The spores contained 4 equal-sized pyriform polar capsules (4.5 x 2.4
      microm), located at the same level, each with a polar filament with 6 (rarely 7)
      coils. Binucleate sporoplasm was irregular in shape, with a granular matrix and
      dense bodies randomly distributed in a light area. Based on the shape and
      dimensions of the spore, on the number, position and arrangements of the surface
      ridges, caudal bundle of filaments, polar capsules and polar filament
      arrangements, as well as phylogenetic analyses using the small subunit ribosomal
      DNA (SSU rDNA) sequences, we propose the name Chloromyxum riorajum for this new
      myxozoan.

PMID- 19593933
TI  - X-cells in pseudotumors of yellowfin goby Acanthogobius flavimanus: a protistan
      organism distinct from that in flathead flounder Hippoglossoides dubius.
AB  - Yellowfin goby Acanthogobius flavimanus affected with X-cell pseudotumors were
      sampled from a river estuary in Tokyo Bay, Japan. We amplified the gene for small
      subunit ribosomal RNA (18S rRNA) of X-cells of the goby with PCR using universal
      primers. The gene that we obtained (DDBJ Accession no. AB451874) showed 91%
      sequence identity to that of the X-cells of the flathead flounder Hippoglossoides
      dubius. With in situ hybridization, the probes specific for the gene that we
      obtained hybridized with the goby X-cells but not with the flounder X-cells,
      whereas probes for the 18S rRNA gene of flounder X-cells hybridized with the
      flounder X-cells but not with goby X-cells. These findings indicate that,
      although the X-cells found in the goby are closely related to the protist found
      in flounder, the two are clearly distinct organisms.

PMID- 19593934
TI  - Effects of skeletal deformities on swimming performance and recovery from
      exhaustive exercise in triploid Atlantic salmon.
AB  - The occurrence of spinal deformity in aquaculture can be considerable, and a high
      rate of deformity has been suggested in triploid smolts in Tasmania. However, the
      physiological performance of fish with skeletal deformities has not been
      addressed. The swimming performance and oxygen consumption of triploid Atlantic
      salmon smolts with either a vertebral fusion (platyspondyly) or multifocal
      scoliosis were compared to normal (non-deformed) triploid smolts. Fish with
      vertebral fusion attained swim speeds similar to normal fish, whereas scoliotic
      fish were unable to attain comparable swim speeds. Routine and maximum oxygen
      consumption was higher for deformed fish compared with normal fish, translating
      into apparent increased routine metabolic scope in vertebral fusion fish, and
      equivocal scope in scoliotic fish compared with normal controls. Deformed fish
      developed a lower excess post-exercise oxygen consumption compared to non
      deformed fish, suggesting they are either incapable of sustained anaerobic
      activity or possess an increased recovery capacity. These data suggest that
      skeletal deformity has differential effects on swimming performance depending
      upon the type of deformity but imposes a significant metabolic cost on salmon
      smolts.

PMID- 19593935
TI  - Effects of temperature and salinity on the survival of Bonamia ostreae, a
      parasite infecting flat oysters Ostrea edulis.
AB  - Bonamiosis due to the intrahaemocytic protistan parasite Bonamia ostreae is a
      European endemic disease affecting the flat oyster Ostrea edulis. The parasite
      has been described in various ecosystems from estuaries to open sea, but no clear
      correlation has yet been demonstrated between disease development and
      environmental parameters. In this study, the effect of temperature and salinity
      on the survival of purified parasites maintained in vitro in seawater was
      investigated by flow cytometry. Purified parasites were incubated in various
      seawater media (artificial seawater, natural seawater, seabed borewater) at
      various temperatures (4, 15 and 25 degrees C) and subjected to a range of
      salinities from 5 to 45 g l(-1). Parasites were collected after 12, 24 and 48 h
      of incubation for flow cytometry analyses including estimation of parasite
      mortality and parasite viability through detection of non-specific esterase
      activities. Artificial seawater appeared unsuitable for parasite survival, and
      results for all media showed a significantly lower survival at 25 degrees C
      compared to 4 degrees C and 15 degrees C. Moreover, high salinities (> or = 35 g
      l(-1)) favoured parasite survival and detection of esterase activities. Flow
      cytometry appears to be a suitable technique to investigate survival and
      activities of unicellular parasites like B. ostreae under varied conditions.
      Although these results contribute to a better understanding of existing
      interactions between the parasite B. ostreae and its environment, validation
      through epidemiological surveys in the field is also needed.

PMID- 19593936
TI  - Multiple dermal lipomas in farmed striped seabream Lithognathus mormyrus on the
      Spanish Mediterranean coast.
AB  - Two cases of multiple dermal lipomas were found in cultured striped seabream
      Lithognathus mormyrus (L.) from the southeast coast of Spain. A histopathological
      study suggests that pigmented cells may correspond to melanomacrophage
      aggregates. The presence of these aggregations is likely related to the
      occurrence of a pathological process of tumoral nature.

PMID- 19593937
TI  - Different degrees of overweight: anthropometric indices in patients with coronary
      heart disease.
AB  - OBJECTIVES: Obesity is a risk factor for all-cause mortality. The obesity
      incidence depends on different definitions. Among patients with high-risk
      coronary heart disease (HRCA), we have studied differences in obesity incidence,
      according to different anthropometric indices. METHODS AND RESULTS: Based on the
      definitions of the International Guidelines Committees for body mass index (BMI),
      waist circumference (WCF), and waist-hip ratio (WHR), we have classified 487 CAD
      patients into 3 groups: normal (group 1), overweight (group 2), and obese
      patients (group 3). Among men, obesity criteria BMI, WCF and WHR were positive in
      17.5%, 14.2%, and 66.4% of the subjects. Among male subjects < 65 years, the
      incidence of HRCA (%), for the 3 groups (normal, overweight, obese) were for BMI
      (2.4, 21.5, 28.9, P = 0.005); WCF (17.9, 12.1, 37.9, P = 0.012); WHR (0, 15.4,
      30.4, P = 0.024). In male subjects > 65 years, for the HRCA incidence (%), only
      WHR showed a significant difference between the 3 groups (0, 15.4, 30.4, P =
      0.024). Among women, 30.6%, 63.6%, and 87.6% were obese by the BMI, WCF, and WHR
      criteria, respectively. We did not find any significant differences in the HRCA
      distribution between age groups and degrees of obesity. CONCLUSIONS: HRCA
      distribution varied among obese male patients. According to the different methods
      of measurement, obesity percentages varied from 4- to 5-fold among men and 3-fold
      among women. In our view,WHR measurement is the method of choice for the
      determination of obesity among patients with CAD.

PMID- 19593938
TI  - Infectious pericarditis: an experience spanning a decade.
AB  - BACKGROUND: Although recent literature suggests a changing spectrum for
      infectious pericarditis (IP), this view has not been proven. In this report, we
      aim to review the features of IP in cases from a large tertiary centre. METHODS:
      A retrospective review of our institution's database was conducted to identify
      cases with IP between January 1994 and December 2004. All pericardial biopsy
      tissue results from the same period were also reviewed. RESULTS: One hundred and
      thirty-eight cases were identified, of which 14 cases were identified by
      pathology. The mean age was 53 +/- 18 years, and 74% were men. The most
      frequently identified causative organisms were Propionibacterium acnes (P.
      acnes), staphylococci and streptococci. A common predisposing factor was an
      immune-compromised state, followed by cardiac surgery. Fifty-five patients were
      treated with antibiotics (medical group) while 63 cases (surgical group)
      underwent surgical drainage (pericardial window) and/or pericardiectomy. In
      comparison to the medical group, the surgical group was more critically ill and
      immunocompromised (40% versus 24%, respectively). There were 52 late deaths
      during follow-up. Mortality in the medical group was 67% while in the surgical
      group it was 24% (P < 0.0001). CONCLUSIONS: In contradistinction to the
      literature reports, the most prevalent organism for IP was P. acnes. Patients
      managed aggressively with both antibiotics and surgery, demonstrated lower
      mortality rates. Therefore, clinicians should maintain a high index of suspicion
      for IP so that timely and appropriate mortality-reducing strategies can be
      offered.

PMID- 19593939
TI  - Acute effect of transcatheter closure on right ventricular function in patients
      with atrial septal defect assessed by tissue Doppler imaging.
AB  - OBJECTIVE: Echocardiographic measurement of right ventricular function in
      patients with atrial septal defect (ASD) is challenging. The Doppler myocardial
      performance index (MPI) may provide a method of assessing function in these
      patients. The aim of this study was to evaluate right ventricular function and
      its changes after transcatheter closure in patients with ASD using MPI by tissue
      Doppler imaging (TDI). METHODS: MPI, defined as the sum of isovolumic relaxation
      and isovolumic contraction time divided by ejection time, was measured by tissue
      Doppler imaging and pulsed Doppler (PD), respectively. Measurement of time
      intervals and MPI with TDI and PD were performed in 46 patients with ASD before
      closure, and at 3 days, 1 month after closure. Twenty-two healthy volunteers
      served as control subjects. RESULTS: Both MPI obtained by TDI and PD increased
      significantly in patients with ASD compared with control subjects (TDI: 0.41 +/-
      0.07 vs. 0.32 +/- 0.04, P < 0.001; PD: 0.41 +/- 0.07 vs. 0.31 +/- 0.04, P <
      0.001). There were highly significant correlations between MPI values obtained by
      TDI and by PD in patients with ASD and in control subjects, respectively (r =
      0.46, P = 0.001; r = 0.72, P < 0.001, respectively). After transcatheter closure,
      the MPI obtained by TDI decreased markedly in patients with ASD (3 days after
      closure: 0.37 +/- 0.06, P = 0.004; 1 month after closure: 0.33 +/- 0.05, P <
      0.001, respectively). CONCLUSIONS: The TDI-derived MPI can be used to assess the
      global right ventricular function in patients with ASD. Compared with control
      subjects, the MPI was significantly higher in patients with ASD suggesting
      decreased right ventricular function. After transcatheter closure, the MPI
      decreased markedly and right ventricular function improved in patients with ASD.

PMID- 19593940
TI  - Global left ventricular function: assessment with dual-source CT versus
      conventional ventriculography in a porcine model.
AB  - OBJECTIVE: Cardiac computed tomography (CT) and conventional biplane
      ventriculography are established methods for the determination of ventricular
      function. Recently dual source CT was introduced for cardiac CT scanning
      providing a temporal resolution of 83 ms independent of the patient's heart rate.
      The purpose of this study was to assess the global left ventricular function
      using retrospectively ECG-gated dual source computed tomography (DSCT) in
      comparison to conventional ventriculography. METHODS AND RESULTS: Contrast
      enhanced cardiac DSCT and conventional ventriculography were performed in 10
      domestic pigs with an approximate weight of 60 kg using standardized examination
      protocols under general anaesthesia. From manually drawn endocardial contours, LV
      end-systolic (ESV) and end-diastolic volume (EDV), stroke volume (SV), ejection
      fraction (EF) were calculated by means of dedicated analysis software separately
      for both examination modalities. LV functional parameters were analysed using
      Bland-Altman plots, Student t-test, and Pearson correlation coefficient. Left ESV
      and EDV determined with DSCT correlated well with conventional ventriculography
      results (ESV: r = 0.86; EDV: r = 0.72) with a good correlation also for SV (r =
      0.67).An only moderate correlation was found for EF (r = 0.52). Student t-test
      showed a significant underestimation of SV and EF derived from DSCT in comparison
      to ventriculography. CONCLUSION: Retrospectively ECG-gated DSCT can accurately
      determine LV volumes in comparison to conventional ventriculography but provides
      lower SV and EF values; however, the correlation was only moderate.

PMID- 19593941
TI  - Omega-3 fatty acid supplements improve the cardiovascular risk profile of
      subjects with metabolic syndrome, including markers of inflammation and auto
      immunity.
AB  - OBJECTIVE: Fish-oil contains high concentrations of omega-3 fatty acids that have
      been shown to have anti-inflammatory properties. We have evaluated the effects of
      purified omega-3 fatty acid supplements on several anthropometric and biochemical
      parameters, including heat shock protein (Hsp) 27 antibody titres in subjects
      with metabolic syndrome. METHODS: Subjects (n = 120) with metabolic syndrome
      (mean age of 52.9 +/- 11.9 years) were randomly allocated to one of two groups:
      sixty subjects were given 1 gram of fish oil as a single capsule, containing 180
      mg eicosapentaenoic acid and 120 mg docosahexaenoic acid daily for 6 months.
      Control subjects did not receive any supplementation over the same period.
      RESULTS: The study was completed by 47 subjects in the intervention group and 42
      subjects in the control group. Treatment with omega 3 supplements was associated
      with a significant fall in body weight (P < 0.05), systolic blood pressures (P <
      0.05), serum low density lipoprotein cholesterol (P < 0.05), and total
      cholesterol (P < 0.05), triglycerides (P < 0.05), high-sensitivity C-reactive
      protein (hs-CRP) (P < 0.01), and Hsp27 antibody titres (P < 0.05). No significant
      changes were observed in the control group. CONCLUSION: It appears that omega 3
      improves the cardiovascular risk profile of subjects with metabolic syndrome,
      having effects on weight, systolic blood pressure, lipid profile and markers of
      inflammation and autoimmunity.

PMID- 19593942
TI  - Increased levels of laminin and collagen type VI may reflect early remodelling in
      patients with acute myocardial infarction.
AB  - OBJECTIVE: The development of left ventricular remodelling (LVR) after acute
      myocardial infarction (AMI) is a predictor of heart failure and mortality. The
      extracellular matrix (ECM) is highly susceptible to ischaemic injury. Laminin and
      collagen type VI (CVI) contribute to ECM formation in the infarct zone. To
      determine whether these markers can be detected in blood samples, we measured
      laminin and CVI in patients with AMI and control subjects. METHODS: A total of 60
      patients scheduled for coronary angiography and 31 patients with AMI were
      included. We subdivided the patients into three groups: (1) AMI, (2) stable
      coronary artery disease (CAD) and (3) exclusion of CAD. Laminin and CVI serum
      concentrations were recorded using the ELISA-technique. RESULTS: Laminin was
      significantly higher in patients with AMI than in subjects with stable CAD (36.5
      vs. 23.9, P < 0.01) or without CAD (36.5 vs. 24.6 ng/ml, P < 0.05). CVI-levels
      were significantly elevated in patients with AMI compared to subjects without CAD
      (7.5 ng/ml vs. 5.4 ng/ml, P < 0.05) or stable CAD (7.5 ng/ml vs. 5.7 ng/ml, P =
      0.01). Laminin and CVI were significantly higher in patients with severely
      reduced left ventricular function. Laminin and CVI values were significantly
      correlated (r = 0.6). CONCLUSION: Our data suggest that laminin and CVI serum
      levels can be potential surrogate parameters of ECM remodelling after AMI. We
      hypothesize that serum laminin reflects early ECM-remodelling involved in the
      process of postischaemic tissue degradation and repair, and CVI may be a marker
      of collagen denaturation and shifts in the collagen phenotype ratios.

PMID- 19593943
TI  - Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
      have no beneficial effect on ablation outcome in chronic persistent atrial
      fibrillation.
AB  - OBJECTIVE: Previous studies have shown that angiotensin-converting enzyme
      inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could reverse
      structural and electrical atria remodelling and decrease atrial fibrillation (AF)
      onset or recurrence. The aim of this retrospective study was to investigate
      whether ACEIs/ARBs had beneficial effects on ablation outcome of chronic
      persistent AF. METHODS AND RESULTS: This study included 139 patients with chronic
      persistent AF who underwent radiofrequency ablation in our centre. Patients were
      divided into an ACEIs/ARBs group or a non-ACEIs/ARBs group. During follow-up
      (14.6 +/- 8.9 months) after AF ablation, AF-free survival in the ACEIs/ARBs group
      was not significantly different from the non-ACEIs/ARBs group (P = 0.339).
      Univariate analysis showed that predictors for AF-free survival were AF history
      (HR, 1.064; 95% CI, 1.021-1.108; P = 0.003) and duration of chronic persistent AF
      (HR, 1.012; 95% CI, 1.005-1.019; P = 0.001). Multivariate analysis showed that
      predictors for AF-free survival were AF history (HR, 1.051; 95% CI, 1.004-1.101;
      P = 0.035) and duration of chronic persistent AF (HR, 1.012; 95% CI, 1.004-1.020;
      P = 0.004). ACEIs/ARBs therapy was not a predictor for AF-free survival neither
      in univariate nor multivariate analysis. CONCLUSION: In this observational study,
      no effect of ACEIs or ARBs was seen on the AF recurrence after ablation of
      chronic persistent AF.ACEIs/ARBs did not help to predict a better ablation
      outcome. Predictors for ablation outcome are AF history and duration of chronic
      persistent AF.

PMID- 19593944
TI  - Evaluation of myocardial bridges with 64-slice computed tomography coronary
      angiography.
AB  - OBJECTIVE: The aim of this study is to report the characteristics of myocardial
      bridging (MB) using 64-slice computed tomography and to demonstrate the
      association between atherosclerotic coronary artery disease (CAD) and MB. METHODS
      AND RESULTS: In 990 consecutive patients who underwent multi-slice computed
      tomography (MSCT) coronary angiography for suspected or known coronary artery
      disease, myocardial bridge evaluation was performed with axial, curved
      multiplanar reconstruction and three-dimensional volume-rendered images. 265
      bridged segments were identified in 223 (22.5%) patients. Multiple MBs on left
      coronary arteries were found in 41 patients. Most of the MBs were in the LAD
      (62.6%), followed by the obtuse marginal artery (14.7%) and diagonal artery
      (14.3%). The average length of MBs was 14 +/- 7 mm, and the average depth was 1.6
      +/- 11 mm. No significant difference was observed between patients with and
      without MB on the middle LAD in respect of age, gender, prevalence of diabetes,
      hyperlipidaemia, hypertension, current smoking and prevalence of atherosclerotic
      plaques at the proximal LAD. On the other hand, prevalence of atherosclerotic
      plaques at the distal LAD were significantly lower in patients with MB on the
      middle LAD (3.5% vs. 19.7%, P: 0.0001). CONCLUSIONS: The presence and
      morphological characteristics of MB and its relation with atherosclerotic plaques
      in the involved coronary artery can be comprehensively analysed with 64-slice
      computed tomography coronary angiography. Atherosclerosis is a common finding in
      segments proximal to MB, but the prevalence of plaques in equivalent segments
      (proximal LAD in our study) is not higher than in patients under similar coronary
      artery disease risk and without MB. On the other hand, prevalence of
      atherosclerotic plaques at the distal LAD was significantly lower in our patients
      with MB on the middle LAD. Finally, we suggest that rather than causing proximal
      atherosclerosis, MB might have a more important role in the protection of distal
      segments of the bridged arteries from atherosclerosis.

PMID- 19593945
TI  - Outcome of patients with dilated cardiomyopathy in a contemporary Swiss
      population.
AB  - OBJECTIVE: Outcome of dilated cardiomyopathy (DCM) has markedly improved due to
      ACE-inhibitors, beta-blockers and implantable defibrillators over the last
      decades. Aims were both the determination of current mortality rates and the
      improvement of left ventricular function over time with regard to different
      baseline factors. METHODS AND RESULTS: The coronary angiography registry was
      screened between 2001 and 2003 for patients with DCM. Those still alive in 2005
      (observation period 38 +/- 13 months) received a questionnaire about symptoms and
      drug therapy. Follow-up echocardiographies were obtained. Death was categorised
      as either sudden, cardiac or non-cardiac. "Full recovery" was defined as normal
      ejection fraction (EF). 128 patients, age 59 +/- 10 years, were identified. EF
      was 30 +/- 11%; 31% were in NYHA class I, 40% in II and 20% in III. 19 patients
      (16%) died, 5 sudden, 5 with heart failure, 9 due to non-cardiac causes. Annual
      mortality rate was 5%, cardiac alone 2.5%. All 5 patients who died suddenly had
      initially an EF of < 30%. Mean EF had improved to 41%, in 18 patients it was
      normal. Neither NYHA class nor therapy were predictors for "recovery", poor EF
      showed a trend to less "recovery" (28 +/- 11% vs. 33 +/- 14%, P < 0.06). There
      were no predictors in patients whose EF rose from below 25% to above 35% as
      compared to those in whom it was stable below 35%. CONCLUSIONS: Under optimal
      medical therapy, symptoms and EF improved in DCM patients. However, annual
      cardiac mortality was still 2.5%, but unfortunately no baseline predictors for
      either death or "recovery" were identified.

PMID- 19593946
TI  - Prevalence of diabetes and impaired fasting glucose in hypertensive adults in
      rural China.
AB  - AIM: The purpose of this study was to estimate the prevalence of diabetes and
      impaired fasting glucose (IFG) and their associated risk factors in the
      hypertensive rural Chinese. METHODS: A cross-sectional survey was conducted
      during 2004-2006 with a cluster multistage sampling design. Data from a
      comprehensive questionnaire, physical examination, and blood tests were obtained
      from a resident group of 6,412 individuals with hypertension, aged > or = 35
      years. RESULTS: The prevalence of diabetes among the hypertensive rural adults
      was 10.0%. The prevalence of IFG was 26.0%, using the new American Diabetes
      Association (ADA) criteria (fasting plasma glucose 5.6-6.9 mmol/l); according to
      the 1997 ADA criteria (fasting plasma glucose 6.1 - 6.9 mmol/l), the prevalence
      of IFG was 9.7%. By using multivariate logistic regression analysis, age, sex
      (male gender), systolic blood pressure, overweight or obesity, total cholesterol
      and triglycerides were determined to be risk factors for diabetes (P < 0.05).
      CONCLUSIONS: This study shows that diabetes and IFG are common among hypertensive
      rural Chinese. In view of the huge number of hypertensive adults in rural China,
      the results of this study emphasize the need to improve the early detection and
      prevention of diabetes in China to prevent the emerging diabetes epidemic.

PMID- 19593947
TI  - Association between -455G/A and fibrinogen in a Chinese population.
AB  - OBJECTIVE: The aim of the study was to evaluate the association between beta
      fibrinogen gene -455G/A polymorphism and the plasma fibrinogen level in Chinese
      patients with different subtypes of coronary heart disease (CHD). METHODS AND
      RESULTS: We investigated beta-fibrinogen gene -455G/A polymorphism and plasma
      fibrinogen level in non-CHD control subjects (n = 466) and CHD patients (n =
      1,019) including patients with stable angina pectoris (SAP) (n = 674), and acute
      coronary syndrome (ACS) (n = 345). Increased plasma fibrinogen levels were
      observed in the CHD groups compared with the control subjects (ACS: 380.92 +/-
      92.35 mg/dl, SAP: 352.49 +/- 94.89 mg/dl, control: 311.72 +/- 87.09* mg/dl, *P <
      0.001 vs. ACS and SAP). Individuals with the -455A/A genotype were associated
      with the highest plasma fibrinogen in the control subjects (P < 0.001) and
      patients with SAP (P < 0.001) but not in patients with ACS (P > 0.05). Allele
      frequency and genotype distribution were similar among the three groups (P =
      0.314). CONCLUSIONS: This study demonstrated that elevated plasma fibrinogen
      level is related to increased CHD risk. The presence of -455A allele is
      significantly associated with higher fibrinogen in non-CHD control subjects and
      SAP patients but not in ACS patients while -455G/A polymorphism is not a risk
      factor for CHD in the Chinese population.

PMID- 19593948
TI  - Elastin gene study of infants with isolated congenital ductus arteriosus
      aneurysm.
AB  - OBJECTIVE: To investigate whether isolated congenital ductus arteriosus aneurysm
      (DAA) is caused by loss of function of mutations in the elastin gene (ELN), we
      screened the elastin gene, which has been proposed as a candidate gene in DAA.
      METHODS AND RESULTS: A total of 2249 full-term neonates received
      echocardiographic screening. Newborns with isolated DAA were divided into two
      groups: those with large DAA (> or = 10 mm) and small DAA (< 10 mm). ELN gene
      study was performed randomly for newborns with DAA. There were 186 (8.3%)
      newborns with DAAs. Among them, 29 had large and 157 had small DAA detected by
      2DE. Maximum internal diameter of the DAAs ranged from 6.6 to 14.0 mm (8.3 +/-
      1.2 mm). All cases were asymptomatic. Fifteen newborns with large DAA and 14 with
      small DAA received ELN gene analysis. Among them, 4 infants had single nucleotide
      variations, including nucleotide 212 C --> T in 2, 278 C --> T in one, and 1232 T
      --> C in one. We considered the possibility that these might be a neutral single
      nucleotide polymorphism rather than a mutation. CONCLUSIONS: The incidence of
      congenital DAA and clinical presentations were consistent with those of our
      previous report. Based on our findings, the ELN gene can be excluded as a
      candidate gene in DAA. We consider the presence of DAA may be a normal variant of
      ductus arteriosus in full-term infants.

PMID- 19593949
TI  - Traditional cardiac risk factors profile in Iranian patients undergoing coronary
      artery bypass surgery.
AB  - OBJECTIVE: It is well known that the traditional cardiac risk factors (TCRFs)
      affect short-term and long-term outcome following coronary artery bypass graft
      surgery (CABG). The objective of this study was to detect the prevalence of these
      risk factors i.e., hypertension, diabetes mellitus, hyperlipidaemia, smoking and
      family history of premature CAD in an Iranian population undergoing coronary
      artery bypass surgery. METHODS AND RESULTS: From March 2001 to September 2005, we
      retrospectively analysed prospectively collected data from our registry. Data
      were achieved regarding TCRFs in 10,622 consecutive patients undergoing elective
      CABG. Mean age of the patients was 58.75 +/- 9.72 years and 74.4% were men. The
      majority of the patients were overweight with a body mass index (BMI) > or = 25.0
      kg/m2. Hyperlipidaemia was present in 63.9% of the patients. Over half of all the
      patients had hypertension and over one third diabetes. History of smoking was
      present in 37.7% of the patients and one third had a family history of CAD. Of
      all the patients, 91.6% had at least one of the TCRFs. As compared to men, women
      were more overweight or obese, and had a greater prevalence of hyperlipidaemia,
      hypertension, diabetes mellitus, and family history of CAD but smoking was much
      more common in men than in women. CONCLUSION: The current study revealed a high
      prevalence of most of TCRFs in an Iranian population that underwent CABG.

PMID- 19593950
TI  - Lipoprotein lipase and premature coronary artery disease.
AB  - OBJECTIVE: This study investigates the relationship between post-heparin plasma
      lipoprotein lipase (LPL) activity, chronic inflammation and premature stable
      coronary artery disease (CAD) in male patients. METHODS AND RESULTS: 132 male
      patients (< 55 years) with documented stable CAD (cases) and 130 male subjects
      without CAD were enrolled. Cases had higher values of high-sensitivity C-reactive
      protein (hs-CRP) and lower LPL activity [(5.31 +/- 3.06) mg/l vs. (2.67 +/- 1.01)
      mg/l, P < 0.01; (27.39 +/- 6.71) nmol x ml(-1) x min(-1) vs. (37.06 +/- 7.22)
      nmol x ml(-1) x min(-1), P < 0.01, respectively]. LPL activity was inversely
      associated with hs-CRP and triglycerides (TG), and positively associated with HDL
      C (r = -0.761, P < 0.001; r = -0.339, P < 0.001; r = 0.217, P < 0.05;
      respectively) in cases. In multivariate analysis, higher values of hs-CRP (OR
      1.45, 95% CI: 1.083-1.951; P = 0.013), BMI, LDL-C and hypertension were
      significant predictors of premature stable CAD in male patients. Higher LPL
      activity decreases risk of premature stable CAD (OR 0.87, 95% CI: 0.809-0.933; P
      = 0.000). LPL activities decreased with the increased number of significantly
      stenosed vessels (P < 0.05). CONCLUSIONS: LPL activity and hs-CRP are significant
      predictors of premature stable CAD in male patients and are inversely correlated.

PMID- 19593951
TI  - Effects of ankylosing spondylitis on the heart.
AB  - BACKGROUND: Various cardiac pathologies have been linked to ankylosing
      spondylitis (AS) in various conflicting reports. OBJECTIVES: A pilot exploration
      is done to search frequencies of structural heart involvement, arrhythmias and
      heart rate variability (HRV) in AS patients. METHODS: Thirty-five AS patients and
      25 healthy people were evaluated with 12-lead electrocardiography,
      echocardiography and 24-hour Holter monitoring. RESULTS: No patient had
      significant valvular heart disease except one. Ventricular and supraventricular
      premature beat counts were significantly higher in AS patients compared to the
      control group (P = 0.002 and 0.01). Frequency of ventricular premature beats was
      significantly correlated with isovolumetric relaxation time (IVRT) (r = 0.291 , P
      = 0.025). Abnormal ECG was defined in 4 AS patients; 2 incomplete right bundle
      branch block (RBBB), one left axis deviation and one complete RBBB and left
      anterior hemiblock. QT and P wave dispersions were not significantly different
      between AS patients and the control group. Although mitral inflow deceleration
      time (DT) and IVRT were significantly longer in AS patients (P < 0.001, both),
      frequency of diastolic dysfunction was not significantly different. Among HRV
      parameters rMSSD (day time), PNN50 (day time) and SDSD (day and night time) were
      significantly lower than the control group. There were weak to moderate but
      significant negative correlations of IVRT and DT with these parameters.
      CONCLUSIONS: In this small sample there is no significant increase in structural
      heart disease in patients with AS. Diastolic functions may be affected in the
      course of disease and this may be associated with increased frequency of
      premature beats. Day time heart rate variability is decreased and associated with
      diastolic function parameters of IVRT and DT in AS patients.

PMID- 19593953
TI  - Prevalence of the metabolic syndrome and its risk factors in Inner Mongolia,
      China.
AB  - OBJECTIVE: To assess the prevalence of the metabolic syndrome and its risk
      factors, Mongolian people from Inner Mongolia were studied. METHODS AND RESULTS:
      2536 participants aged 20 years or above from Tongliao city in Inner Mongolia
      were selected for a cross-sectional study. Lifestyle risk factors, body weight,
      height, waistline, hipline, fasting plasma glucose, blood lipids, and C-reactive
      protein (CRP), were investigated in all participants. They were divided into
      metabolic syndrome and non-metabolic syndrome groups. Risk factors were graded
      from two to four. The standardized prevalence rate of the metabolic syndrome was
      17.1%, lower in men (11.4%) than in women (21.6%) (P < 0.001). In men, with
      multivariate logistic regression, total cholesterol in the highest grade, hip
      circumference in the highest grade, waist-to-hip ratio and body mass index were
      associated with the metabolic syndrome. In women, LDL-cholesterol, C-reactive
      protein in the highest grade, hip circumference, waist-to-hip ratio and body mass
      index were associated with the metabolic syndrome. There is no relationship
      between cigarette smoking, alcohol drinking and metabolic syndrome in men or
      women. CONCLUSION: In Mongolian people of agricultural and pasturing areas in
      Inner Mongolia, China, the prevalence of metabolic syndrome is higher in women
      than in men. Hip circumference, waist-to-hip ratio and body mass index are
      significantly associated with the metabolic syndrome.

PMID- 19593952
TI  - CTSS promoter -25G/A: not a risk factor for CHD in Chinese.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory disease characterized by extensive
      remodelling of the extracellular matrix architecture of the arterial wall. Recent
      data suggested the participation of lysosomal cysteine proteases such as
      cathepsin S (CTSS) in atherogenesis. The G/A polymorphism at nucleotide -25 was
      reported to be located in the promoter of the CTSS gene. The aim of this study
      was to observe the association between CTSS -25G/A polymorphism and the risk of
      coronary heart disease (CHD) in a Chinese population sample. METHODS: The
      polymerase chain reaction and restriction digestion methods were performed to
      screen the CTSS gene -25G/A polymorphism in a Chinese population sample with (n =
      659) or without CHD (n = 352). Traditional risk factors for CHD were obtained
      simultaneously. RESULTS: The frequencies of the G and A allele in the total
      population was 0.630 and 0.370, respectively. The frequencies of -25G/A
      polymorphism in the CTSS gene (G: 0.626 vs. 0.633, P > 0.05; A: 0.374 vs. 0.367,
      P > 0.05) and the genotype distribution (G: 83.4 vs. 85.3, P > 0.05; A: 58.0 vs.
      58.5, P > 0.05) were similar between CHD patients and control subjects. Moreover,
      CTSS genotype was not associated with severity of coronary stenosis (P > 0.05) in
      CHD patients. CONCLUSION: The CTSS -25G/A polymorphism was not related with CHD
      in our Chinese population sample.

PMID- 19593954
TI  - The influence of rosuvastatin therapy and percutaneous coronary intervention on
      angiogenic growth factors in coronary artery disease patients.
AB  - OBJECTIVE: The aim of our investigation was to assess the influence of
      rosuvastatin therapy and myocardial revascularization on angiogenic growth
      factors in coronary artery disease patients. METHODS AND RESULTS: Two main groups
      were examined: group one consisted of patients with successful percutaneous
      coronary intervention and group two consisted of patients 3 months on
      rosuvastatin therapy.Vascular endothelial growth factor (VEGF), VEGF receptor Flt
      1 (sVEGF-R1) and transforming growth factor beta-1 (TGF-beta1) levels were
      measured in healthy volunteers and CAD patients before and 6 days after
      myocardial revascularization.VEGF and basic fibroblast growth factor (bFGF)
      levels were measured before and 3 months after rosuvastatin therapy, as well as
      total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol
      (LDLC), high-density lipoprotein cholesterol (HDLC), C-reactive protein (CRP),
      interleukin 6 (IL-6) and endothelium-dependent vasodilation. VEGF levels did not
      differ, but beta-TGF levels were significantly lower in CAD patients in
      comparison with healthy subjects, P < 0.0001. Myocardial revascularization caused
      changes of VEGF levels from 192.4 +/- 166.1 pg/ml to 264.7 +/- 226.6 pg/ml (P =
      0.0066). There were positive changes in lipid levels, lowering of CRP and IL-6
      concentrations, improving of endothelial function and decreasing of VEGF levels
      from 382 +/- 249 pg/ml to 297 +/- 220 pg/ml (P = 0.006) 3 months after
      rosuvastatin treatment. CONCLUSIONS: There is an elevation of VEGF levels early
      after myocardial revascularization that may reflect a transient ischaemia and
      potentially may provoke atherosclerotic plaque neovascularization. Rosuvastatin
      leads to a decrease of VEGF levels that can be a reflection of the influence on
      endogenous angiogenesis. There was no correlation between inflammatory factors
      and VEGF that gives a suggestion about an absence of direct CRP and IL-6 impact
      on VEGF decreasing during statin treatment.

PMID- 19593955
TI  - Subacute total occlusion of the left main coronary artery.
AB  - Total occlusion of left main coronary artery (LMCA) is a rare manifestation of
      coronary atherosclerotic disease. The exceptionality of this illness is due to
      its high mortality rate before any treatment. We report a patient with subacute
      total occlusion of the LMCA.

PMID- 19593956
TI  - Risks and benefits of replacing conventional plasma lipids with apolipoprotein
      measurement.

PMID- 19593957
TI  - Improved myocardial perfusion preceding clinical response on bosentan treatment
      for coronary vasospasm.
AB  - Many patients suffer from persistent angina due to coronary vasospasm despite
      optimal medical treatment. We treated a 46-year-old patient with severe and
      treatment-resistant coronary vasospasm with the endothelin-receptor antagonist
      bosentan. Using oxygen-15-labelled water in conjunction with oxygen 15-labelled
      carbon monoxide positron emission tomography (PET), we measured an impaired
      coronary flow reserve (CFR) in 6 out of 13 segments directly before the start of
      bosentan therapy. A repeated PET measurement after 16 weeks of bosentan revealed
      a completely normalized CFR in this patient. Furthermore, the patient reported
      less frequent and less severe chest pain. Our data suggest a potential role of
      endothelin-receptor antagonists for patients with severe coronary vasospasms.

PMID- 19593959
TI  - Sinus node dysfunction after surgical repair of an atrial septal defect (secundum
      type): worth the wait.
AB  - Sinus node dysfunction after surgical repair of an atrial septal defect is a
      rather uncommon complication. We report a case of protracted post-operative sinus
      node dysfunction which was managed successfully by oral theophyllines and
      'watchful' waiting. This strategy could avoid placement of a permanent pacemaker
      in this patient group of younger age.

PMID- 19593958
TI  - Paroxysmal bidirectional ventricular tachycardia with tachycardiomyopathy in a
      pregnant woman.
AB  - Palpitations in pregnancy are not an uncommon complaint. We present a case of
      palpitations in the third trimester related to bidirectional ventricular
      tachycardia with evidence, of left ventricular systolic dysfunction. The case was
      successfully managed with flecainide therapy and urgent elective caesarean
      section. The rhythm stabilised to sinus rhythm and left ventricular systolic
      function normalised. We discuss the possible underlying diagnosis of
      catecholaminergic polymorphic ventricular tachycardia with resultant
      tachycardiomyopathy. A literature review of bidirectional ventricular tachycardia
      is presented. This is the first reported case of bidirectional VT producing LV
      systolic dysfunction, which normalised following stabilisation of rhythm. The
      complex issues of management of this case in particular with regard to the
      pregnancy are discussed.

PMID- 19593960
TI  - Unexpected complete aortorenal occlusion.
AB  - In chronic aorto-iliac occlusive disease, pre-existing renal artery stenosis may
      give rise to sufficient development of collateral blood flow and prevent
      ischaemic symptoms for a long time and therefore may cause delay in diagnosis. An
      early diagnosis of aorto-iliac disease is necessary in order to avoid fatal
      outcome. Duplex scanning is generally used to rule out a renal artery stenosis.
      This can generally detect the occlusion, but has some drawbacks such as obesity
      gas interposition, accessory renal arteries or the anatomy of the left renal
      artery, which may hinder complete examination of both renal arteries and may give
      rise to misdiagnosis. On the other hand, CT may provide detailed anatomic
      information. In this paper, we present a case of total aortorenal occlusion
      mimicking renal artery stenosis on duplex scanning.

PMID- 19593961
TI  - Artery of Adamkiewicz-sparing endovascular stent placement.
AB  - We report a case of successful endovascular treatment of an acute, uncomplicated
      Stanford type B aortic dissection, sparing the artery of Adamkiewicz. The ECG
      gated MSCT diagnosed the reason for the acute chest pain in the patient, and
      identified the intercostal artery from which the artery of Adamkiewicz
      originated, thus permitting the positioning of the stent-graft well away from it.
      Ten months after successful stent-graft implantation the patient was well, the
      haematoma in the formerly dissected aortic wall had been almost completely re
      absorbed and the false lumen had disappeared. A kink and fold of the stent-graft
      due to the concave path of the distal aortic arch remained stable and free of
      thrombi.

PMID- 19593962
TI  - How many times can a heart be broken?
AB  - Stress-induced cardiomyopathy, apical ballooning syndrome, 'broken heart'
      syndrome or takotsubo cardiomyopathy are different names of the same condition,
      with the number of reported cases increasing. It mimics an acute myocardial
      infarction, with extensive ventricular dysfunction, with minimal cardiac enzyme
      elevation and without significant coronary disease found with angiography. It has
      been linked to acute emotional or physical stress, hence the name stress-induced
      cardiomyopathy. This syndrome can be recurrent, as illustrated in this case
      report.

PMID- 19593964
TI  - Update on the use of nitric oxide as a noninvasive measure of airways
      inflammation.
AB  - Nitric oxide levels may reflect the inflammatory status of both the upper and
      lower airways. Measurement of exhaled bronchial nitric oxide is a useful, non
      invasive tool in the diagnosis and management of eosinophilic asthma. Nasal
      nitric oxide may be normal, raised or lowered in disease states; however
      measurement may be a useful tool in the diagnosis and management of patients with
      chronic rhinosinusitis, nasal polyps, and cystic fibrosis, as well as in the
      diagnosis of primary ciliary dyskinesia. Further research is aimed at
      investigating the role of nitric oxide in allergic rhinitis and nasal congestion.
      Measuring both bronchial and nasal nitric oxide may assist the combined
      management of upper and lower airways.

PMID- 19593963
TI  - Outcome measurements in clinical research, does it matter?

PMID- 19593965
TI  - Three dimensional measurement of rhinoplasty results.
AB  - BACKGROUND: Pre- and postoperative imaging is important and essential for
      evaluation of the results of rhinoplasty surgery. Two-dimensional photographs are
      used routinely for this purpose, but have several disadvantages as opposed to
      three-dimensional imaging techniques, such as stereophotogrammetry. This study is
      the first to describe the measurement of rhinoplasty results using
      stereophotogrammetry. The aim of this study was to evaluate the ability of 3D
      imaging to measure and objectify rhinoplasty results. METHODS: During a 6-month
      period all consecutive hump reduction patients were included in this prospective
      study. Pre- and postoperative 3D photographs were taken and compared. RESULTS:
      Twelve patients were studied. In ten of these twelve patients a significant
      volume reduction in the area of the nasal dorsum was found with
      stereophotogrammetry. The maximum decrease (i.e. lowering) of the nasal dorsum
      ranged from 0.8 to 4.4 mm. In two patients no reduction of the nasal dorsum was
      found. In both patients this was due to additional changes made to the nose
      during surgery. These changes, increased tip rotation and dorsal augmentation
      respectively, were also documented with stereophotogrammetry. CONCLUSIONS: Both
      pronounced as well as subtle postoperative changes of rhinoplasty surgery can be
      objectified and measured with stereophotogrammetry. This tool can be used to
      study whether surgical techniques have the desired effect on the nose, and to
      compare different techniques with each other.

PMID- 19593966
TI  - Digital volume tomography in the diagnosis of nasal bone fractures.
AB  - Digital volume tomography (DVT) is a kind of cone beam computed tomography and
      enables high quality 3D images of osseous structures. It is a well-established
      diagnostic tool in dentistry. High detail resolution is reached with a reduced
      exposition of radiation dose in comparison to conventional computed tomography.
      The data volume can be analysed in three orthogonal plains, which can be changed
      in angle arbitrarily. The aim of the study was to evaluate, if and in which
      performance DVT is able to detect discrete nasal bone fractures that cannot be
      seen in conventional radiography occasionally. DVT was performed in sixty-five
      patients with suspected nasal bone fracture. Five of these patients underwent
      lateral radiographs of the nasal bones in other departments which failed to show
      any radiologic signs of a nasal bone fracture, whereas DVT showed clear fracture
      lines. DVT-findings were also used to classify fractures according to their
      dimensions. Additionally DVT enabled the reconstruction of three-dimensional
      volume images. With this technique it is possible to get an image of the extent
      of the nasal bone fracture and the dislocation of the fragments. Because of these
      facts as well as its high resolution and low radiation dose, DVT can be
      recommended as the routine radiological examination in suspected nasal bone
      fractures.

PMID- 19593967
TI  - Tip rhinoplasty--a modified delivery approach.
AB  - INTRODUCTION: For many cases of tip surgery a delivery approach is selected. If
      the patient has long alar cartilages, it may be difficult to deliver the
      cartilages without twisting or tearing the domes. In such a patient, a modified
      delivery approach may be easier to perform. METHODS: For the modified delivery
      approach a transcartilaginous incision is first made and cephalic resection of
      the alar cartilage is performed. Then a marginal incision is made, and the
      remaining alar cartilage is dissected and easily delivered. After both alar
      cartilages being delivered, they are compared, and, if necessary, further
      resection is done in order to achieve perfect symmetry or to achieve the desired
      size of the cartilages. The cartilages may then be grafted, sutured or modified
      as considered necessary. RESULTS: We have been using the modified delivery
      approach for the last five years and we have had no complications of the
      technique itself. Two patients operated on by using this approach are presented.
      CONCLUSION: We believe that, in patients with long alar cartilages and a wide
      nasal tip, this modification turns the delivery approach into an easier and safer
      approach.

PMID- 19593968
TI  - Where endoscopy fails: indications and experience with the frontal sinus fat
      obliteration.
AB  - BACKGROUND: With the event of angled endoscopes, image guidance and the rapidly
      improving endoscopic techniques the previously used osteoplastic frontal sinus
      fat obliteration (ISO) becomes more and more a second line treatment option. The
      objective of our study is to describe the up-to-date indications for FSO based on
      our own experience. METHODS: Retrospective analysis including follow-up visits of
      77 patients with frontal sinus fat obliteration at our clinic between 1991 and
      2006 was undertaken and descriptive statistics were drawn. RESULTS: Thirty-six
      cases were operated by FSO as a first-line treatment, 41 had previous surgery.
      Eighty percent of all patients showed no postoperative residual complaints. Two
      patients required revision surgery. General complication rate was 36.4%, however
      these consisted in the vast majority of cases (90%) of minor complications.
      CONCLUSIONS: FSO still remains a valuable operation for specific indications. FSO
      is the gold standard for repeatedly failed endoscopic procedures. The operation
      should also target the following indications as a first-line treatment:
      large/lateral osteomas, malignant disease, lateral mucoeceles, most fractures of
      the posterior sinus wall with CSF-leak, osteomyelitis, pathologies in small
      underdeveloped sinuses with narrow floor. It is associated with minimal
      complications and a good outcome.

PMID- 19593969
TI  - Use of nasal bivalve septal teflon splint for the treatment of recurrent
      epistaxis in patients undergoing anticoagulant therapy.
AB  - Management of recurrent epistaxis in patients on anticoagulant therapy is a
      challenging problem. In this article, we report our experience concerning the use
      of bivalve septal teflon splint (BSTS) for the treatment of recurrent mild
      epistaxis in a group of patients who underwent anticoagulant therapy after
      cardiac valve surgery. The study included 18 patients whose epistaxes recurred
      despite standard methods such as local pressure, vasoconstrictors, sedation,
      packing or cauterization. BSTS was sutured on the both sides of the nasal septum
      and held in place during one month. Epistaxis was controlled in all of the
      patients. We believe that the use of BSTS is an effective, easily applied, non
      traumatic, well-tolerated additional method for the treatment of recurrent mild
      epistaxis in patients undergoing anticoagulant therapy, when other conventional
      treatments fail. Further controlled studies with larger groups are warranted in
      order to further evaluate this method.

PMID- 19593970
TI  - Histological and radiological signs indicative for chronic sinus mucosal
      inflammation in Graves' ophthalmopathy.
AB  - Orbital decompression and, in some cases, decompression of the optic nerve are
      the principal surgical procedures used for treatment of moderate or severe
      Graves' orbitopathy (GO). Histological examination of the surgical specimens of
      the ethmoid revealed a wide spectrum of inflammatory mucosal changes. The charts
      of 68 GO patients (55 female and 13 male; age range: 14 - 85 years) were
      retrospectively reviewed. Lund - Mackay scores were calculated for each patient
      based on findings of pre-operative computer tomography (CT) sinus scans, and the
      incidence of histological changes associated with polypoid and eosinophilic
      inflammation was assessed. Files did not reveal any evidence of chronic
      rhinosinusitis with or without nasal polyps based on endoscopic findings. Sinus
      opacification on CT (of any extent) was found in 20 out of the 68 patients
      (29.4%). On histological exam, histological changes of the sinus mucosa
      indicative for chronic rhinosinusitis were found in 31 out of the 68 GO patients
      (45.5%). A histological examination of the sinus mucosa indicative for chronic
      polypoid inflammation was present in 25 patients. Fourteen out of these 25
      patients showed mucosal tissue eosinophilia on histology. Six patients had
      mucosal changes suggesting chronic non-polypoid inflammation with tissue
      eosinophilia on histological exam. The incidence of chronic rhinosinusitis in
      individuals without GO ranges between 10 and 15%. The incidence of histological
      changes of the sinus mucosa indicative for chronic rhinosinusitis described in
      this investigation suggests that chronic inflammatory disease is considerably
      more frequent in GO patients, when compared to the incidence of chronic
      rhinosinusitis in individuals without GO. Additionally, our data underline that
      CT imaging of the paranasal sinuses underestimates (29.4%) the incidence of
      inflammatory changes of the sinus mucosa (45.5%) of any extent in GO patients.

PMID- 19593971
TI  - Peripheral and central levels in nasal trigeminal sensitization and
      desensitization.
AB  - In order to investigate the role of central and peripheral mechanisms in nasal
      trigeminal sensitization/desensitization processes, the present work recorded
      psychophysical (intensity ratings) and psychophysiological (skin conductance)
      responses to allyl isothiocyanate volatile nasal stimulation--during normal
      breathing--in monorhinal condition after a controlateral stimulation of the other
      nostril. Insofar as both nostrils are anatomically separated, modifications in
      responses can be interpreted as a central regulation process. Results showed that
      sensitization was clearly related to central mechanisms contrarily to
      desensitization which depended only of peripheral level.

PMID- 19593972
TI  - Effects of laserneedle acupuncture on olfactory sensitivity of healthy human
      subjects: a placebo-controlled, double-blinded, randomized trial.
AB  - The aims of the present study were to investigate the influence of laserneedle
      acupuncture on olfactory sensitivity and to examine whether the attitude towards
      laserneedle acupuncture affects the outcome. Olfaction was tested repeatedly on
      two days using the olfactory detection threshold subtest of the Sniffin' Sticks
      test battery in sixty-four healthy subjects of which 32 showed a positive
      attitude towards the effects of laserneedle acupuncture and 32 were sceptic about
      its effects. Testing was accomplished three times on day one (T1 = 0 min, T2 = 35
      min, T3 = 105 min) without laserneedle acupuncture and on day two (T1* = 0 min,
      T2* = 35 min, T3* = 105 min) when the subjects were randomized in a non
      stimulation (placebo) and a stimulation (laserneedle acupuncture) group.
      Stimulation or non-stimulation was conducted in a double-blinded design.
      Following laserneedle acupuncture a significant decrease in olfactory detection
      thresholds was observed at both, T2* and T3*, whereas no significant changes were
      found in the baseline or placebo group. Effects of laserneedle acupuncture on the
      olfactory detection threshold did not differ between sceptic and non-sceptic
      subjects. In conclusion, laserneedle acupuncture is an effective method to
      improve olfactory sensitivity after one session of stimulation for at least one
      hour, independently of the attitude of subjects towards the stimulation method.

PMID- 19593973
TI  - Olfactory detection thresholds and pleasantness of a food-related and a non-food
      odour in hunger and satiety.
AB  - The primary aim of this study was to investigate whether olfactory detection
      thresholds are dependent on different states of satiety. Using the threshold test
      of the Sniffin' Sticks test battery (single-staircase, three alternative forced
      choice procedure), sensitivity to a non-food odour (n-butanol) and a food-related
      odour (isoamyl acetate) was investigated. Twenty-four healthy, female subjects
      (mean age 24.2 years, SD 2.7 years) with normal olfactory function performed the
      tests when hungry and when satiated. Additionally, they rated their emotional
      condition, arousal, alertness as well as the intensity and pleasantness of both
      odorants. No significant change in the detection thresholds for the non-food
      odour n-butanol, but a significant change in detection threshold for the food
      related odour isoamyl acetate was found. The detection threshold for isoamyl
      acetate was significantly lower in the state of satiety compared to the hungry
      condition. As expected, the perceived pleasantness of isoamyl acetate was
      significantly lower in satiety. In summary, the results indicate that in our
      experimental setting the actual state of satiety has effects on detection
      thresholds of a food-related odour, but not of a non-food odour. Interestingly,
      the higher sensitivity was found during the state of satiety challenging the
      current hypothesis that control of food intake is supported by a decrease in
      sensitivity to food odours. Instead our findings that satiety decreases the
      pleasantness of a food-related odour support the hypothesis that both odour
      threshold as well as pleasantness play an important role in the control of food
      intake.

PMID- 19593974
TI  - Percutaneous embolization on hereditary hemorrhagic telangiectasia patients with
      severe epistaxis.
AB  - OBJECTIVES: To evaluate the results of embolization in patients with hereditary
      hemorrhagic telangiectasia (HHT) because of severe epistaxis. METHODS: All HHT
      patients who underwent an embolization (between 1992 and 2006) were asked to
      participate in this retrospective study. Twelve patients who had in total 19
      embolization procedures were interviewed. A questionnaire was used assessing the
      frequency, severity, duration of epistaxis and their Impact on Lifestyle (IoL).
      Haemoglobin values were collected from the patients' records. Embolization of the
      pathologically enhancing lesions was performed using PVA particles. RESULTS: The
      direct effect of the embolization is very good in 95% of patients. The Impact
      factor (daily frequency x severity) of epistaxis improved in the first month (p =
      0.000) and one year after embolization (p = 0.009). Eleven embolizations (61%)
      were still associated with significant improvement. There was a reduction in the
      duration of epistaxis by 16 minutes per day one month after embolization (p =
      0.005). However, this reduction was not found one year after embolization. Mean
      haemoglobin rose significantly after 1 year by an average of 0.8 mmol/l (p =
      0.045). Impact on Lifestyle improved in 68% of the procedures and was unchanged
      in 32%. CONCLUSION: Embolizations remain a therapeutic option in experienced
      hands. The indication should be made carefully, because of possible (major)
      complications.

PMID- 19593975
TI  - Evaluation of prognostic factors for olfaction in nasal polyposis treated by
      endoscopic sinus surgery.
AB  - AIM: This prospective study aimed to assess treatment outcome on olfaction in
      patients undergoing Endoscopic Sinus Surgery (ESS) for nasal polyposis, and to
      evaluate the role of previous sinus surgery and the duration of olfactory deficit
      as prognostic factors for olfaction improvement. METHODS: In total, 116 patients
      with nasal polyposis who underwent ESS were studied. Olfactory testing was
      performed using the Sniffin' Sticks test, preoperatively and 1-, 3- and 6-month
      postoperatively. RESULTS: The values of the composite threshold discrimination
      identification score were significantly lower in patients with long duration of
      olfactory deficit and history of previous sinus surgery in all testing sessions.
      Adjustment for preoperative olfactory measures and all potential confounders
      revealed that both parameters remained strong independent predictors of normal
      olfactory function; a successful outcome was more frequent in patients with short
      duration of olfactory deficit and in patients who had not undergone previous
      sinus surgeries. However all patients achieved a significant stepwise increment
      of all indices of olfactory function over time, after ESS. CONCLUSIONS: Duration
      of olfactory deficit and previous sinus surgery presented highly significant
      predictive value for the short-term outcome of the olfactory function after ESS.
      However all patients suffering from nasal polyposis will probably improve
      olfaction significantly in a period up to six months after surgery.

PMID- 19593976
TI  - Correlation between symptoms and radiological findings in patients of chronic
      rhinosinusitis: a modified radiological typing system.
AB  - BACKGROUND: CT scan and nasal endoscopy are increasingly being used in diagnosing
      and treating patients of chronic rhinosinusitis. Though CT scan accurately
      depicts the sinus pathology its use as a proxy in assessing the symptom severity
      of patients is debatable. In this study the symptom severity of chronic
      rhinosinusitis was correlated with the author's modified CT scan score. METHODS:
      The study involved the examination of symptom severity and CT scan scores of a
      series of 240 adult patients with chronic rhinosinusitis. The CT scans were
      evaluated and scored as per author's modified CT scan staging. The pathology at
      ostiomeatal complex was analysed for its association with severity of symptoms.
      RESULTS: The mean CT score of group B patients (8.35) was found to be
      significantly higher than patients of group A (3.22). In maxillary and frontal
      sinus there was a statistically significant association of group B patients
      (moderately severe and severe symptoms) with stage IV of CT scan stage. Although
      the symptom score of patients with pathology at the ostiomeatal complex on CT
      scan was found to be higher in group B there was no correlation with anatomical
      variations at the ostiomeatal complex. CONCLUSIONS: The study group showed a
      statistically significant increase in the sinus involvement and CT scan scores
      with increasing symptom severity. The study indicates a strong association
      between the symptom severity of chronic rhinosinusitis patients with CT scan
      scores, with the scores calculated using modified CT scoring criteria. These
      criteria would help the clinician to accurately predict symptom severity by CT
      scan scores.

PMID- 19593977
TI  - Increased serum complement component 3 and mannose-binding lectin levels in adult
      Chinese patients with chronic rhinosinusitis.
AB  - OBJECTIVE: To study the immune function of adult Chinese patients with chronic
      rhinosinusitis (CRS) to elucidate its potential role in the pathogenesis of CRS.
      METHODS: A prospective three-arm case-control study. The study population
      comprised 72 CRS patients without nasal polyps (NPs), 95 CRS patients with NPs,
      and 110 healthy controls. The concentrations of serum immunoglobulin A (IgA), M
      (IgM), G (IgG), IgG subclasses (IgG1-4), complement component 3 (C3), and
      complement component 4 (C4) were measured by nephelometry. Serum mannose-binding
      lectin (MBL) levels were analyzed by enzyme-linked immunosorbent assay. All CRS
      patients had a complete blood count with differential, atopic status evaluation,
      coronal computed tomographic (CT) scan of the sinuses, and nasal endoscopy.
      RESULTS: Frequency of immunoglobulin, C3, C4, or MBL deficiency showed no
      difference among groups. The prevalence of coexistence of MBL and immunoglobulin
      or complement component deficiency did not differ significantly among groups
      either. However, compared with controls, decreased IgG3 levels were found in CRS
      patients without NPs, and increased C3 and MBL levels was found in both CRS
      patients with and without NPs. Moreover, MBL levels were significantly higher in
      CRS patients with NPs than in CRS patients without NPs, which positively
      correlated with extent of disease seen on CT scan and endoscopy, and peripheral
      eosinophil count. CONCLUSIONS: Immunoglobulin, C3, C4, and MBL deficiency is not
      the main cause of CRS in adult Chinese patients. However, on the contrary,
      increased C3 and MBL levels in serum might play a modulatory role in CRS
      development.

PMID- 19593978
TI  - Diminished response to grass pollen allergen challenge in subjects with
      concurrent house dust mite allergy.
AB  - INTRODUCTION: The clinical manifestation of allergic rhinitis is influenced by
      many factors; while different subpopulations are not well defined. Different
      combinations of allergic sensitization may lead to different clinical
      manifestations of allergic disease. METHODS: In a nasal allergen challenge model
      we compared allergic rhinitis symptoms between subjects mono-sensitized to grass
      pollen or house dust mite, poly-sensitized subjects, and healthy controls. We
      measured visual analogue scales of symptoms and peak nasal inspiratory flow. We
      also compared serum total IgE, allergen-specific IgE and IgG4, and basophil
      histamine release. RESULTS: Nasal challenge with grass pollen extract led to a
      significantly larger increase in subjective (p = 0.031) and objective (p = 0.001)
      nasal symptoms in grass pollen mono-sensitized subjects than in poly-sensitized
      subjects. No differences were found in serum levels of allergen-specific IgE and
      IgG4 or in biological activity of IgE (basophil histamine release) between mono
      sensitized and poly-sensitized subjects. We found a strong inverse correlation
      between serum allergen-specific IgE and basophil histamine release (-0.789, p =
      0.001). CONCLUSIONS: Grass pollen mono-sensitized subjects have a more severe
      clinical response to nasal challenge than poly-sensitized subjects. This cannot
      be explained by serum levels of IgE or its biological activity. The continuous
      allergen exposure in poly-sensitized subjects may alter local immuno-regulatory
      processes, leading to a reduced clinical response to allergen challenge.

PMID- 19593979
TI  - Remodeling of nasal mucosa by allergen exposure in guinea pigs is suppressed by
      steroid and pranlukast.
AB  - BACKGROUND: It is unclear whether remodeling exists in allergic rhinitis in man.
      The aim of this study was to establish a guinea pig model of allergic rhinitis
      with remodeling and to examine the effects of dexamethasone and pranlukast on
      nasal mucosa remodeling. METHODS: In the first experiment, three groups of
      ovalbumin-sensitized Hartley guinea pigs received intranasal challenges with
      ovalbumin for 1, 8, 12 weeks, respectively. In the second experiment, to examine
      the effect of dexamethasone and pranlukast, the animals were divided into 4
      groups: negative control group; ovalbumin-sensitized group; ovalbumin +
      dexamethasone group; and ovalbumin + pranlukast group. During 12 weeks of
      intranasal exposure to ovalbumin, the latter two groups received daily
      intraperitoneal injections of dexamethasone and pranlukast, respectively.
      RESULTS: In the first experiment, in contrast to the negative control group, the
      ovalbumin-sensitized group exhibited significant goblet cell hyperplasia,
      epithelial damage and deposition of extracellular matrix in the nasal septal
      mucosa and conchae. In the second experiment, these changes were significantly
      inhibited by dexamethasone and pranlukast, respectively. CONCLUSIONS: We have
      established a model of upper airway remodeling in guinea pigs. The tissue
      remodeling was inhibited by early intervention with the antiallergic-inflammatory
      agents dexamethasone and pranlukast.

PMID- 19593980
TI  - Asthma is more frequently associated with non-allergic than allergic rhinitis in
      Portuguese patients.
AB  - BACKGROUND: Rhinitis prevalence is increasing worldwide and is frequently
      associated with asthma, for which it is a risk factor. The aims of the study were
      to characterise the adult population with rhinitis attending the Cova da Beira
      Hospital Allergy Clinic, and to assess the relationship between rhinitis and
      asthma. METHODS: In total, 686 patients were characterised by clinical history
      and anterior rhinoscopy, and classified according to international guidelines.
      Atopy was determined by skin prick testing to aeroallergens and quantification of
      specific IgE. RESULTS: Seventy two percent of patients had allergic rhinitis
      (AR), and 28% had non-allergic rhinitis (NAR). NAR was more frequently associated
      with older age, perennial symptoms and female gender. NAR patients more
      frequently had bronchial asthma. In addition, more NAR than AR patients also had
      drug allergy, pharyngitis, sinusitis and urticaria. AR patients with nasal polyps
      more frequently had asthma. Grass pollen and mites were the major sensitisers for
      AR patients. Sensitisation profiles were not significantly different between
      urban- and rural-based AR patients. CONCLUSIONS: Asthma was more frequently
      associated with non-allergic than with allergic rhinitis. The two types of
      rhinitis did not differ in clinical severity. Although sensitisation profiles
      were not different between the urban and rural patients, allergic rhinitis
      prevalence was higher in urban patients.

PMID- 19593981
TI  - An unusual case of firearm injury to the face with bullet cover lodged in the
      nose.
AB  - We report an unusual case of an accidental firearm injury, in a 35-year-old male
      firearm trainer, by a bullet cover fired in a retrograde manner, which was lodged
      in his right nasal cavity just reaching sphenoid sinuses without any neurological
      impairment. The extent of tissue damage and posterior extent of tract was
      assessed by plain radiography and CT scans. The bullet cover was recovered under
      endoscopic guidance and the wound sutured with a small defect left for healing by
      secondary intention keeping in mind second stage reconstruction of the persisting
      defect. On follow up the wound had healed with good esthetic results. The case
      showed that gunshot injuries can be treated primarily as well that undermining of
      the edges of wound and regular well-lubricated dressings are key to good healing.

PMID- 19593982
TI  - Bilateral allergic fungal rhinosinusitis caused by Schizophillum commune and
      Aspergillus niger. A case report.
AB  - Schizophillum commune (S. commune) is a rare type of basidiomycetous fungus that
      has being reported as a cause of allergic fungal rhinosinusitis (AFRS), invasive
      type of fungal sinusitis and allergic bronchopulmonary mycosis (ABPM). However,
      it is believed that S. commune was often misdiagnosed to Aspergillus sp. We
      report a case of bilateral nasal polyps and maxillary, ethmoidal and sphenoidal
      involvement within the context of S. commune and Aspergillus niger associated
      AFRS. Our patient was suffering from a chronic disease with periods of remission
      and exacerbation and was treated successfully by a combination of surgical and
      antifungal treatment. In our experience, S. commune may be found frequently in
      patients with AFRS. AFRS, including the S. commune-associated type, usually runs
      a prolonged course and can affect any paranasal sinus. Surgical treatment alone
      is not sufficient and must be combined with medical treatment.

PMID- 19593983
TI  - Strain differences of cerebral ventricles in mice: can the MRL/MpJ mouse be a
      model for hydrocephalus?
AB  - Hydrocephalus is an intractable disease characterized by the excessive
      accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles. There are
      many cases in both human and animals; however, the cause and mechanism of it's
      development is not clearly understood. In this study, differences of cerebral
      ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c)
      were investigated by histological techniques to determine the possibility of a
      new animal model for hydrocephalus. Our analysis showed that significant
      differences in the volume and the surface area of lateral ventricles in the 5
      inbred strains, with MRL/MpJ mice having the largest lateral, third, aqueduct and
      fourth ventricles. In addition, when MRL/MpJ mice were compared to BALB/c mice on
      0 day after birth, the former already had larger lateral ventricles than the
      latter. Although there were no significant difference in the ratios of ependymal
      cell types in MRL/MpJ mice and BALB/c mice, the number and the diameter of lipid
      droplets in MRL/MpJ mice were, interestingly, smaller than those in BALB/c mice.
      It is well known that ependymal cells absorb nutritional substances in CSF by
      endocytosis, suggesting the possibility that their decrease may relate to the
      larger cerebral ventricles in MRL/MpJ. In conclusion, MRL/ MpJ mice have greater
      volumes in cerebral ventricles than other strains and may be useful for a model
      showing high susceptibility to hydrocephalus.

PMID- 19593985
TI  - [English writing mechanics for andrological papers need standardization among
      Chinese authors].
AB  - Mechanics play as essential a role as language presentation is the English
      writing of an andrological paper, and directly influence its quality and
      publication. They, however, frequently fail to receive due attention. In view of
      the typical problems among Chinese authors in English writing, and with a wide
      range of SCI included medical journals for reference, the author draws on his
      experience as an English editor for medical journals and introduces some most
      important and practical English writing mechanics, aiming to contribute to
      further standardization and improvement of Chinese authors'English writing of
      andrological as well as other medical papers.

PMID- 19593984
TI  - Change in body weight of mothers and neonates and in milk composition during
      denning period in captive Japanese black bears (Ursus thibetanus japonicus).
AB  - Japanese black bears, Ursus thibetanus japonicus, have been classified as a
      vulnerable species so that data on reproduction are needed to maintain and/or
      extend their population. They are known to have a peculiar style of reproduction,
      giving birth to their neonates and raising them during denning, a period of
      complete fasting. In this study, we investigated the metabolic rate and milk
      composition of mother bears raising neonates, and the changes in body weight of
      the neonates under captive conditions. Seven female bears kept in dens were
      weighed once a month, and the amount of energy they used was calculated. From
      birth, cubs were also weighed and their growth rate was determined. In addition,
      the milk composition was analyzed to investigate its characteristics. As a
      result, it was found that mother bears used 34% more energy than did solitary
      females. There was no significant difference in the energy used for nursing
      whether they had single or twin cubs. On the other hand, the body weight gain of
      single cubs was significantly higher than that of twin cubs, suggesting that the
      growth of the cubs was highly affected by the suppression of mother's energy
      consumption during the fasting period. The milk had high fat and low sugar
      concentrations. This indicates that mother bears used the fat accumulated prior
      to denning for their main energy source when raising cubs. Considering all
      results together, Japanese black bears showed remarkable efficiency in the use of
      energy for reproduction during the fasting period.

PMID- 19593986
TI  - [Experimental varicocele affects VEGF and Flt-1 protein expressions in the testis
      and epididymis of adolescent rats].
AB  - OBJECTIVE: To investigate the effects of experimental left varicocele (ELV) on
      the vascular endothelial growth factor (VEGF) and its receptor fms-like tyrosine
      kinase-1 (Flt-1) proteins in the testis and epididymis of adolescent rats, and to
      find out the correlation of the two proteins with varicocele-induced male
      infertility. METHODS: We established the ELV model in adolescent male SD rats,
      and detected the expressions of VEGF and Flt-1 proteins in the testis and
      epididymis by immunohistochemistry at 2 and 4 weeks after surgery. RESULTS: Cell-
      and region-specific expressions of VEGF and Flt-1 were observed in the testis and
      epididymis of the ELV and control groups. Statistical analysis showed that, in
      comparison with the corresponding control groups, the 2- and 4-week ELV groups
      exhibited a notable increase in the VEGF protein expression in the hibateral
      testis and epididymis (P < 0.01, P < 0.05); the Flt-1 expression was obviously
      upregulated in the hibateral testis and epididymis of the 2-week ELV group (P <
      0.01, P < 0.01), but remarkably reduced in the hibateral testis and left
      epididymis of the 4-week ELV group (P < 0.01, P < 0.05), with no statistic
      difference in the right epididymis (P > 0.05). CONCLUSION: ELV can cause changes
      in the expressions of VEGF and Flt-1 proteins in the testis and epididymis of
      adolescent rats, and consequently affect spermatogenesis and spermiotelcosis,
      which may be one of the causes of varicocele-induced male infertility or
      subfertility.

PMID- 19593987
TI  - [Expression of the voltage-dependent anion channel gene in human ejaculated
      spermatozoa].
AB  - OBJECTIVE: To identify the genes involved in sperm motility. METHODS: We
      hybridized asthenospermia and normal motile sperm cDNA samples with the human
      whole genome Affymetrix chip to screen differentially expressed genes. Then we
      detected the mRNA expressions of the voltage-dependent anion channel genes
      (VDACs) in human organs and spermatozoa by RT-PCR and compared their expressions
      in the poor and normal motility spermatozoa. RESULTS: Differentially expressed
      genes VDACs were identified by analysis of the hybridization signals, including
      the 3 subtypes VDAC1, VDAC2 and VDAC3. The expression of VDAC2 mRNA was
      significantly decreased in the poor motility sperm (0.568 +/- 0.036), as compared
      with the healthy men (0.803 +/- 0.043, P < 0.01). CONCLUSION: The decreased
      expression of VDAC2 in the ejaculated spermatozoa is possibly associated with the
      reduction of sperm motility.

PMID- 19593988
TI  - [Diagnosis and treatment of genitourinary infection with non-gonococcal Neisseria
      in men].
AB  - OBJECTIVE: To explore the influence of non-gonococcal Neisseria on the diagnosis
      and treatment of male genitourinary infection. METHODS: The samples of urethral
      exudates, prostatic secretions or/and semen were collected from 8 cases of male
      patients with acute urethritis or chronic prostatitis, then inoculated into
      gonococcal agar medium, blood agar medium, Sabouraud agar medium and Mycoplasma
      agar medium, respectively. Neisseria gonorrhoeae, Mycoplasmae, fungi and other
      bacteria were isolated, Chlamydiae examined by Gemenez staining, and the gram
      negative diplococci from the samples identified by oxidase test, biochemical
      examination and drug sensitivity test. The PCR products of the cryptic plasmid
      pJD1 gene of the isolated strains were amplified for the identification of
      Neisseria gonorrhoeae. Based on the results of drug sensitivity tests,
      intravenous or oral antibiotics were selected for treatment. RESULTS: Eight
      strains of gram-negative diplococci were isolated in this study, 3 identified as
      N. mucosa, 4 as N. cinerea and the other 1 as N. lactamica. The PCR
      identification test of the cryptic plasmid pJD1 gene showed the same positive
      results in all the strains as in N. gonorrhoeae. The non-gonococcal Neisseria
      isolated from the male genital tract secretions exhibited a multidrug resistance,
      especially to quinolones and fosfomycin. All the symptoms disappeared and no
      pathogens were detected in the patients after a 7-day treatment with
      Cephalosporins or/and Minocycline. CONCLUSION: Some Neisseria species normally
      parasitizing the upper respiratory tract can also cause male genitourinary
      infections, such as gonorrhea-like urethritis and chronic prostatitis. Neisseria
      gonorrhea could be clinically and etiologically misdiagnosed through such
      conventional methods as morphological examination, oxidase test and PCR
      identification test of cryptic plasmid and other nonspecific genes. Intravenous
      and/or oral antibiotic medication based on the results of drug sensitivity tests
      can cure acute urethritis and chronic prostatitis induced by non-gonococcal
      Neisseria in males. Drug resistance of non-gonococcal Neisseria directly affects
      the success of treatment.

PMID- 19593989
TI  - [Carbendazim affects testicular development and spermatogenic function in rats].
AB  - OBJECTIVE: To explore the effects of carbendazim on the testicular development
      and spermatogenic function of male rats and its action mechanism. METHODS: Forty
      clean-grade impubic male Wistar rats were equally randomized into a low-dose, a
      medium-dose, a high-dose and a control group, treated respectively with
      carbendazim at 20, 100 and 200 mg/kg (bw) and Tween-80 solution, all by oral
      gavage once a day for 80 days. After treatment, the rats were weighed, their
      testes and epididymides immediately excised, their morphological changes observed
      and the weights of the right testis and epididymis obtained. Sperm motility and
      counts in the left cauda epididymis were determined. Histopathological changes,
      cell apoptosis and the expression of Bcl-2/Bax in the testis were detected by HE
      staining, TUNEL and immunohistochemical SABC method. RESULTS: The medium- and
      high-dose groups showed obviously atrophic testes and epididymides, marked
      histopathological abnormality of the testis, reduced weight of the right testis
      and epididymis, and decreased sperm motility and counts in the left cauda
      epididymis (P < 0.01). With the increasing dose of carbendazim, the apoptosis
      rate and Bax expression were significantly raised, while the expression of Bcl-2
      significantly decreased (P < 0.05, P < 0.01). CONCLUSION: Carbendazim affects the
      testicular development and spermatogenic function of male rats, and the mechanism
      may involve cell apoptosis induced by down-regulation of Bcl-2 and up-regulation
      of Bax.

PMID- 19593990
TI  - [Estrogen reduces the expressions of ryanodine receptor type 1 and Cav1.3 L-type
      calcium channel in the vaginal smooth muscle cells of rats].
AB  - OBJECTIVE: To determine the expressions of ryanodine receptor type 1 (RyR1) and
      Cav1.3 L-type calcium channel (Cav1.3) in the vaginal smooth muscle cells of
      castrated rats and investigate the correlation of RyR1 and Cav1.3 with estrogen
      in female sexual dysfunction. METHODS: Forty female SD rats of 8 weeks were
      randomly divided into Groups A (2-week sham operation), B (4-week sham
      operation), C (2-week castration) and D (4-week castration). Two and 4 weeks
      after surgery, the serum estradiol level was determined with the automated
      immunochemiluminescence system and the expressions of RyR1 and Cav1.3 in the
      vaginal smooth muscle were detected by immunohistochemistry and RT-PCR. Gray
      scale ratio was used to represent the mRNA expression levels of RyR1 and Car1.3,
      and the optical density value to denote their protein expression levels. RESULTS:
      Serum estradiol was significantly decreased in Group C ([0.210 +/- 0.026] nmol/L)
      as compared with A ([0.505 +/- 0.053] nmol/L) (P < 0.01), and so was it in Group
      D ([0.130 +/- 0.031] nmol/L) in comparison with B ([0.476 +/- 0.058] nmol/L) (P <
      0.01). RyR1 and Cav1.3 were expressed in all groups. The mRNA expressions of RyR1
      and Cav1.3 were significantly reduced in Group C (0. 680 +/- 0.073 and 0.580 +/-
      0.043) as compared with A (0.950 +/- 0.064 and 0.870 +/- 0.019) (P < 0.01), as
      well as in Group D (0.220 +/- 0.032 and 0.190 +/- 0.020) in comparison with B
      (0.890 +/- 0.072 and 0.820 +/- 0.021) (P < 0.01). The protein expressions of RyR1
      and Cav1.3 were significantly down-regulated in Group C (96.67 +/- 7.75 and 87.97
      +/- 6.96) as compared with A (123.69 +/- 10.66 and 106.46 +/- 8.04) (P < 0.01),
      and so were they in D (86.45 +/- 8.16 and 69.43 +/- 8.30) in comparison with B
      (109.31 +/- 9.87 and 97.38 +/- 7.56) (P < 0.01). CONCLUSION: Both RyR1 and Cav1.3
      were expressed in the vaginal smooth muscle cells of the rats, and estrogen might
      be involved in the regulation of female sexual reaction by acting on the
      expressions of RyR1 and Cav1.3.

PMID- 19593991
TI  - [Effects of nanosized titanium dioxide on the reproductive system of male mice].
AB  - OBJECTIVE: To investigate the in vivo effects of nanosized titanium dioxide
      (TiO2) on the main organs, particularly the reproductive system, of male mice.
      METHODS: Forty-five male ICR mice aged 6 weeks were equally and randomly divided
      into 2 experimental groups and a control group, intraperitoneally injected with
      200 and 500 mg/kg nanosized TiO2 and equal volume of saline, respectively, every
      other day for 5 times. One week after drug cessation, we obtained the
      coefficients of the main organs, serum biochemical parameters and the levels of
      gonadal hormones (T and E2), analyzed the pathological changes of the main organs
      by HE staining, observed sperm count, motility and abnormality under the
      microscope, and detected germ cell apoptosis by TUNEL. RESULTS: Compared with the
      control, the low-dose (200 mg/kg) group showed no significant changes in the
      above parameters, while the high-dose (500 mg/kg) group exhibited a decrease in
      the coefficients of the liver, heart and kidneys, and a significant increase in
      such serum biochemical parameters as ALT, ALT/AST and BUN (P < 0.05). The high
      dose group also showed significantly reduced sperm density and motility,
      increased sperm abnormality and germ cell apoptosis (P < 0.05), but no obvious
      pathological changes in the liver, kidney spleen, testis and epididymis.
      CONCLUSION: Low-dose nanosized TiO2 has no obvious effect on male mice, but high
      dose may significantly reduce their sperm count and function and induce germ cell
      apoptosis, although its damage on the liver and kidney function is slight.

PMID- 19593992
TI  - [ZnPP IX and L-NAME reduce the cGMP content in the penile tissue of rats].
AB  - OBJECTIVE: To investigate the effects of CO release inhibitor zinc protoporphyria
      IX (ZnPP IX) and NO release inhibitor L-NAME on the content of cGMP in the penile
      tissue of rats. METHODS: Thirty Wistar rats were randomly divided into a normal
      control, a ZnPP IX, and an L-NAME group, given saline (1 ml/kg/d), ZnPP IX (45
      micromol/kg/d) and L-NAME (50 mg/kg/d), respectively, for 7 days. Then all the
      rats were killed, homogenate made from their penile tissues and detected for the
      contents of NOS, NO, CO and cGMP. RESULTS: The contents of CO, NOS, NO and cGMP
      were all reduced in both the ZnPP IX and L-NAME groups as compared with the
      control group (P < 0.05). CONCLUSION: ZnPP IX and L-NAME can reduce the
      concentrations of CO and NO in the penile tissues of rats, and consequently the
      content of cGMP.

PMID- 19593993
TI  - [One-stage phallic reconstruction with extended pudendal-thigh flap: a desirable
      surgical option].
AB  - OBJECTIVE: To investigate the feasibility of one-stage phallic reconstruction
      with the extended pudendal-thigh flap (EPTF) to achieve a higher survival rate,
      shorter surgical cycle, and more experimental evidence for the clinical
      application of the technique. METHODS: We equally randomized 36 healthy adult New
      Zealand rabbits to an experimental and a control group to receive one-stage
      phallic reconstruction, the former with EPTF (pudendal-thigh flap + thigh
      cutaneous branches of the superficial external pudendal artery, PTF + TCB), the
      urethra reconstructed with the TCB flap, and the latter with bilateral pudendal
      thigh flaps. RESULTS: The survival rate of the reconstructed phallus was 83.33%
      (15/18) and the urine leakage was 55.56% (10/18) in the experimental group, as
      compared with 38.89% (7/18) and 72.22% (13/18) in the controls. CONCLUSION: One
      stage phallic reconstruction with EPTF, with its higher survival rate and shorter
      surgical cycle, is a desirable substitute for phallic reconstruction with
      bilateral pudendal-thigh flaps.

PMID- 19593994
TI  - [Alternating magnetic field damages the reproductive function of murine testes].
AB  - OBJECTIVE: To explore the relationship between physical and biological effects of
      alternating magnetic field and study the influence of the magnetic field on the
      reproductive function of murine testes. METHODS: Thirty ICR mice were randomized
      into 5 groups: normal control, X-ray radiation, weak magnetic field (1000 Hz), 1
      h strong magnetic field and 2 h strong magnetic field (2000 Hz). The mice were
      sacrificed at 7 days after the exposure for the analysis of testicular sperm
      motility, observation of histopathological changes in the testis by HE staining
      and evaluation of the changes by modified Johnsen grade criteria. RESULTS: The
      rates of sperm motility were (42.37 +/- 10.24)% in the normal control group,
      (39.00 +/- 12.35)% in the X-ray radiation group, (36.00 +/- 17.28)% in the weak
      magnetic field group, (10.72 +/- 5.67)% in the 1 h strong magnetic field group
      and (4.44 +/- 2.87)% in the 2 h strong magnetic field group, respectively.
      Johnsen's scores decreased and the testis damage increased in a dose- and time
      dependent manner. CONCLUSION: Magnetic field, either strong or weak, may damage
      the testis function by inducing injury to seminiferous tubules and Leydig cells,
      thickening of the basal membrane, derangement, exfoliation, massive apoptosis and
      necrosis of spermatogenic cells in the lumen, situation of the epididymis, and
      consequently the absence of sperm.

PMID- 19593995
TI  - [Expression of high mobility group protein A in male mouse testicular cell
      lines].
AB  - OBJECTIVE: To detect the expression of high mobility group protein A (HMGA) in
      male mouse testicular cell lines TM4, GC-1spg and GC-2spd(ts), and to pave the
      theoretical ground for further investigation of the action mechanism of the HMGA
      gene in male mouse spermatogenesis. METHODS: We detected the expressions of HMGA1
      and HMGA2 by RT-PCR and Western blot in the male mouse testicular cell lines TM4,
      GC-1spg and GC-2spd(ts). RESULTS: HMGA1 and HMGA2 were expressed in the male
      mouse testicular cell lines TM4, GC-1spg and GC-2spd(ts) at both mRNA and protein
      levels. Western blot and RT-PCR methods showed similar results. CONCLUSION: The
      expression of HMGA may be involved in the cell division and proliferation of TM4,
      GC-1spg and GC-2spd(ts) and play an important role in spermatogenesis of male
      mice.

PMID- 19593996
TI  - [Combination of short-period sperm-oocyte coincubation and early rescue
      intracytoplasmic sperm injection after total failure of in vitro fertilization].
AB  - OBJECTIVE: To evaluate the outcome of the combination of short-period sperm
      oocyte coincubation with early rescue intracytoplasmic sperm injection (ICSI)
      after complete failure of in vitro fertilization (IVF). METHODS: We used short
      period sperm-oocyte coincubation and overnight fertilization for the oocytes
      obtained from 10 IVF-ET cycles, and compared the fertilization results and embryo
      quality. We conducted polar body observation following short-period sperm-oocyte
      coincubation for 105 conventional IVF cycles, and evaluated the clinical outcome
      of early rescue ICSI for total fertilization failure. RESULTS: No significant
      differences were noted in fertilization outcome and embryo quality between the 3
      h short-period and overnight fertilizations (P > 0.05). The combined strategy
      achieved a clinical pregnancy rate of 53.3%, an implantation rate of 38.0%, with
      64 babies born, of whom 44.8% were taken home. CONCLUSION: The combination of
      short-period sperm-oocyte coincubation with early rescue ICSI can significantly
      improve the clinical outcome in patients who have experienced complete failure of
      in vitro fertilization.

PMID- 19593997
TI  - [Urethral guidance probe applied to surgical urethral realignment].
AB  - OBJECTIVE: To search for a safe and convenient surgical method for management of
      urethral disruption. METHODS: We performed urethral realignment for 18 cases of
      posterior urethral disruption and 4 cases of ruptured bulbous urethra using the
      urethral guidance probe following bladder puncture stoma. RESULTS: Urethral
      realignment was accomplished in 21 of the cases, 18 under epidural and 3 under
      local anesthesia, with the mean blood loss of 20 ml and the average operation
      time of 18 minutes. Open surgery was necessitated in 1 case due to the
      complication of bladder rupture. Routine postoperative urethral dilation extended
      for 3 months, and all the cases were followed up for 3 to 24 months. The maximum
      urine flow rate was 15-22 ml/s in 13 cases and 10-14 ml/s in 7. One case received
      urethral anastomosis 3 months later because of urethrostenosis. CONCLUSIONS:
      Urethral realignment with the urethral guidance probe is a safe, convenient and
      effective surgical strategy for the management of urethral disruption.

PMID- 19593998
TI  - [Vasectomy not associated with prostate cancer: a meta-analysis].
AB  - OBJECTIVE: To evaluate the association between vasectomy and prostate cancer.
      METHODS: We searched comprehensively the databases, CBMDisc, CMCC, CMAC, CNKI
      (from 1978 to January 6, 2009), and PubMed (from 1965 to January 6, 2009) using
      the key words "vasectomy" and "prostate cancer", screened the retrieved
      literature according to the inclusion and exclusion criteria, performed a Meta
      analysis with the software RevMan 4.2 after identification of the relevant data,
      and calculated the overall pooled OR (95% CI) as well as that of the association
      of prostate cancer with <20 and > or =20 yr vasectomy. RESULTS: A total of 20 088
      cases and 232 506 controls in 27 reports (7 cohort and 20 case-control studies)
      were included in this investigation. The overall pooled OR (95% CI) was 1.10
      (0.97-1.24), and those of <20 and > or =20 yr vasectomy were 0.94 (0.83-1.06) and
      1.05 (0.90-1.23), respectively. CONCLUSION: No existing literature show any
      positive association between vasectomy and prostate cancer.

PMID- 19593999
TI  - [Expression, distribution and biological function of leptin receptor in the
      testis].
AB  - Leptin, a 167-amino acid peptidic hormone encoded by the obese gene, is known to
      be involved in the regulation of body fat, energy expenditure, immune function,
      angiogenesis, inflammatory reaction, the onset of puberty, and the regulation of
      reproductive function. The roles of leptin vary with different expression and
      distribution patterns of its receptor Ob-R. This article analyzes the biological
      effects of leptin and its receptor on the testis by reviewing the expression and
      distribution of Ob-R in different cells during different developmental stages or
      in different physiological and pathological states in the testis of men, mice or
      rats.

PMID- 19594000
TI  - [Updated relationship between microRNA and reproduction].
AB  - MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules, about
      22 nucleotides in length, and highly conserved in evolution. They participate in
      a variety of important biological processes, including the development,
      differentiation, and apoptosis of eukaryotes. Recent studies have discovered that
      miRNAs play important roles in the development of primordial germ cells,
      spermatogenesis, and the process of fertilization.

PMID- 19594001
TI  - [Effects of glycosides of Tripterygium wilfordii and Cistanche deserticola on the
      fertility of male mice].
AB  - OBJECTIVE: To study the impact of glycosides of tripterygium wilfordii (GTW) on
      fertility, and the reversibility of this impact following intervention with
      cistanche deserticola (CD) and after withdrawal of GTW. METHODS: Ninety adult
      male KM mice were equally and randomly divided into 9 groups: 5 GTW groups,
      treated with GTW at 45.0, 30.0, 22.5, 15 and 7.5 mg/kg x d, respectively, 2 CD
      groups, administered GTW at 30.0 and 7.5 mg/kg x d, respectively, a drug
      withdrawal group, given GTW at 30.0 mg/ kg x d, and a control group, given 1% CMC
      solution, all intragastrically for 20 days. Then they were mated with female mice
      at the ratio of 1:2 for 7 days, followed by another 20 days of medication, the
      GTW groups at the same doses, the CD groups given CD additionally at 10.0 g/kg x
      d and 2.5 g/kg x d respectively, and the withdrawal group given 1% CMC solution
      only. Again they were mated with the same females, and the pregnancy rate was
      observed after each mating. RESULTS: The pregnancy rate dropped with the increase
      of the dose and medication time of GTW, which was 0% at 40 d in the 45.0 mg/kg x
      d GTW group (P < 0.01), but rose from 25% at 20 d to 55% at 40 d in the 10.0 g/kg
      x d CD group, and from 25% at 20 d to 56 % at 40 d in the withdrawal group.
      CONCLUSION: The reproductive toxicity of GTW acts on male mice in a time- and
      dose-dependent manner, which can be reduced by Cistanche deserticola. The
      fertility of the male mice can be restored to normal 20 days after the cessation
      of GTW.

PMID- 19594002
TI  - [Safety and tolerance of tadalafil in the treatment of erectile dysfunction].
AB  - The benefit of tadalafil should be justified by its safety and tolerance in the
      chronic treatment of erectile dysfunction (ED) in general and high-risk
      population. The main treatment-emergent adverse events, chiefly induced by the
      interactions of tadalafil with PDE5 and isoforms, are mild or moderate in
      severity, transient and reversible, which may disappear without drug withdrawal.
      Tadalafil does not add to the risk and severity of cardiovascular problems, and
      can be safely co-administered with antihypertensives and selective a-receptor
      blockers.

PMID- 19594003
TI  - [Comparative study of posterolateral conventional and minimally invasive total
      hip arthroplasty].
AB  - OBJECTIVE: To compare the clinical effect of total hip arthroplasty (THA) using
      posterolateral conventional or minimally invasive incision. METHODS: From January
      2007 to November 2007, 38 patients (41 hips) were treated with minimally invasive
      THA (mini-incision group), and 15 patients (15 hips) underwent conventional THA
      (conventional incision group). Mini-incision group: 23 males (25 hips) and 15
      females (16 hips) aged (53.2 +/- 15.5) years old; body mass index (BMI) was 23.4
      +/- 3.3; there were 20 cases (20 hips) of femoral neck fracture, 2 cases (2 hips)
      of primary osteoarthritis, 14 cases (16 hips) of stage III or IV aseptic necrosis
      of the femoral head, 2 cases (3 hips) of ankylosing spondylitis involving hip
      joint; Harris hip score was 47.7 +/- 5.5 and the course of disease was (4.5 +/-
      4.3) years. Conventional incision group: 7 males (7 hips) and 8 females (8 hips)
      aged (54.8 +/- 10.8) years old; BMI was 26.1 +/- 5.1; there were 8 cases (8 hips)
      of femoral neck fracture, 1 case (1 hip) of primary osteoarthritis, 5 cases (5
      hips) of stage III or IV aseptic necrosis of the femoral head, 1 case (1 hip) of
      ankylosing spondylitis involving hip joint; Harris hip score was 51.2 +/- 4.3 and
      the course of disease was (3.8 +/- 3.7) years. There were no statistically
      significant differences between two groups in the general information (P > 0.05).
      RESULTS: There were statistical differences between two groups in terms of
      incision length, perioperative blood loss, drainage volume and blood transfusion
      volume (P < 0.05), and no statistical differences were evident in operative time,
      abduction angle and the anteversion angle of acetabular cup (P > 0.05). All
      incisions healed by first intention and no early postoperative complications
      occurred. Two groups were followed for 12-22 months (average 18.3 months). All
      patients walked without the crutch at 2-3 months after operation. The Harris
      score of the mini-incision group and the conventional incision group 6 months
      after operation was 88.6 +/- 3.6 and 85.8 +/- 3.3, respectively, indicating there
      was no significant difference between two groups (P > 0.05), but there was
      significant difference between before and after operation (P < 0.05). CONCLUSION:
      Compared with conventional THA, the minimally incisive using posterolateral
      approach THA has the merits of mini invasion, slight hemorrhage, short hospital
      stay, minor complication, convenient management of femoral head and accurate
      prosthesis location. However, strict attention should be paid to operative
      indications.

PMID- 19594004
TI  - [Cause analysis and clinical management of postoperative wound complications
      after total knee arthroplasty].
AB  - OBJECTIVE: To investigate the causes and the clinical treatment methods of
      postoperative wound complications following total knee arthroplasty (TKA).
      METHODS: From June 2005 to August 2008, 486 cases (576 knees, including 314 left
      knees and 262 right knees) underwent primary TKA using standard midline incision
      and medial parapatellar arthrotomy. There were 146 males (172 knees) and 340
      females (404 knees) aged 51-86 years old (average 61.3 years old). The duration
      of disease was 3-35 years. Primary diseases included: 138 cases (156 knees) of
      rheumatoid arthritis, 282 cases (348 knees) of osteoarthritis, 46 cases (49
      knees) of traumatic arthritis, 20 cases (23 knees) of pigmented villonodular
      synovitis. The factors of etiology, deformity correction, duration of tourniquet
      use and wound drainage were analyzed to determine the cause of postoperative
      wound complication. RESULTS: Postoperatively, 37 cases (43 knees) had wound
      complications and the rate of incidence was 7.5%, including 13 cases (15 knees)
      of aseptic exudation, 3 cases (4 knees) of fat liquefaction, 4 cases (4 knees) of
      subcutaneous hematoma, 8 cases (9 knees) of flap margin necrosis, 6 cases (7
      knees) of superficial infection, 3 cases (4 knees) of red swollen joint with
      increased skin temperature and deep infection. All 37 patients recovered after
      symptomatic treatment. Among those 37 cases, patients with rheumatoid arthritis
      had a higher incidence rate of wound complication than the patients with other
      primary diseases (P < 0.05). The incidence rate of patients with deformity
      correction more than or equal to 20 degree was significantly higher than that of
      other patients (P < 0.05). The duration of using tourniquet was (86 +/- 15)
      minutes for patients with wound complication, and (78 +/- 8) minutes for patients
      without wound complication, indicating there was a significant difference (P <
      0.01). Wound complication occurred in 22 knees (5.1%) with autologous blood
      transfusion absorber, 11 knees (11.5%) with negative pressure attraction, and 10
      knees (19.2%) receiving no drainage. The incidence rate of postoperative wound
      complication in patients without drainage was obviously higher than that in
      patients with drainage (P < 0.05). CONCLUSION: Patients with rheumatoid arthritis
      are more likely to have wound complication after TKA. Postoperative wound
      drainage and short duration of tourniquet application help decrease the incidence
      of complications. It is necessary to make early definitive diagnosis of
      postoperative wound complication, and provide proactive treatment.

PMID- 19594005
TI  - [Treatment of intra-articular calcaneal fracture by bone grafting and plastic ti
      alloy plate internal fixation].
AB  - OBJECTIVE: To investigate the therapeutic effect of open reduction, bone
      grafting, and internal fixation with plastic ti-alloy plate on intra-articular
      calcaneal fracture. METHODS: From January 2005 to December 2007, 32 patients (37
      feet) with intra-articular calcaneal fracture underwent open reduction, bone
      grafting of autogeneic ilium (30-80 g) and internal fixation of plastic ti-alloy
      plate. There were 21 males and 11 females aged 18-56 years old (average 42.1
      years old). There were 5 cases of bilateral calcaneal fracture and 27 cases of
      unilateral calcaneal fracture, including 2 cases of open fracture and 30 cases of
      close fracture. According to Sanders classification system, there were 11 cases
      of type II, 18 cases of type III and 8 cases of type IV. Preoperatively, Bohler
      angle was (-9.6 +/- 4.2) degree and Gissane angle was (101.4 +/- 10.6) degree.
      Nine feet underwent emergency operation and 28 feet received operation 5-7 days
      after injury. RESULTS: The wounds of 34 feet healed by first intention. The wound
      margin of 3 feet was gray with a small amount of colorless exudates, and healed
      after dressing change. All patients were followed for 12-24 months (average 16
      months). X-ray films displayed that the fracture all healed within 3-4 months
      after operation. At 6 months after operation, the Bohler angle and the Gissane
      angle was (28.5 +/- 6.1) degree and (128.9 +/- 4.8) degree, respectively,
      indicating there were significant differences when compared with before operation
      (P < 0.05). According to Maryland foot score system, 15 cases were graded as
      excellent, 18 cases were good, 4 cases were poor, and the excellent and good rate
      was 89.19%. CONCLUSION: Open reduction, bone grafting, and internal fixation with
      plastic ti-alloy plate is an effective method to treat intra-articular calcaneal
      fracture. Choosing right operational timing, performing subarticular surface
      grafting when necessary and using appropriate plastic ti-alloy plate internal
      fixation can minimize the incidence of postoperative complications.

PMID- 19594006
TI  - [Effect evaluation of treating Freiberg's disease with dorsal wedge osteotomy and
      absorbable pin fixation].
AB  - OBJECTIVE: To investigate the operative technique of treating Freiberg's disease
      with dorsal wedge osteotomy and absorbable pin fixation, and to evaluate the
      clinical outcome. METHODS: From June 2005 to June 2007, 8 patients with
      Freiberg's disease were treated, including 2 males and 6 females aged 16-66 years
      old (average 36 years old). X-ray films revealed osteosclerosis, collapse of the
      metatarsal head and ischemic necrosis of the second metatarsal head. According to
      Smillie classification system, there were 4 cases of stage II, 3 of stage III and
      1 of stage IV. The duration of symptoms was 6-36 months (average 19 months).
      After dorsal wedge osteotomy, the metatarsal heads were rotated to reconstrust
      the joint surface, then 3-4 pieces of absorbable pin 1.5 mm in length were
      implanted for fixation. RESULTS: All wounds healed by first intention, and no
      early postoperative complications occurred. Five patients were followed for 11-35
      months (average 14 months) and had significant pain relief. At 3 months after
      operation, the dorsal-flexion of metatarsophalangeal joint was improved by 0-50
      degrees (average 21 degrees), and the plantar-flexion was increased by 0-10
      degrees (average 5 degrees). X-ray films showed that solid union of the osteotomy
      was achieved in all patients at 8-13 weeks after operation (average 10 weeks).
      Average shortening of metatarsal was 1.7 mm (range 1.3-2.0 mm). All patients
      returned to sports and recreational activities at 4 months after operation,
      except one case of stage IV who had constant swelling and stiffness in the joint
      and was improved at 12 months after operation. CONCLUSION: Dorsal wedge osteotomy
      in complex with absorbable pin fixation is an effective procedure for stage II
      and III Freiberg's disease, because it is capable of reconstructing the
      metatarsophalangeal joint effectively, allowing early joint motion and avoiding a
      second operation.

PMID- 19594007
TI  - [Repair of acromioclavicular dislocation with clavicular hook plate internal
      fixation and coracoacromial ligament transposition].
AB  - OBJECTIVE: To explore the operative method and the clinical outcomes of repairing
      acromioclavicular dislocation by clavicular hook plate internal fixation and
      coracoacromial ligament transposition. METHODS: From August 2004 to December
      2007, 12 cases of acromioclavicular dislocation were repaired with the internal
      fixation of clavicular hook plate and the transposition of coracoacromial
      ligament. There were 9 males and 3 females aged 22-56 years old (average 32 years
      old). Causes of injury: 6 cases from falling injury, 4 cases from crush injury
      and 2 cases from traffic accident. There were 5 cases of the left
      acromioclavicular dislocation, and 7 cases of the right. According to
      acromioclavicular dislocation classification set by WANG Yicong, 8 cases were
      graded as type III, 3 cases as type IV, and 1 case as type V. The time from
      injury to operation was 3-28 days (average 6 days). The injured arm was hung
      after operation, and the function training was started 3-5 days after operation.
      RESULTS: All wounds healed by first intention, and the X-ray films showed
      complete reposition of acromioclavicular joints was achieved in all cases 1 week
      after operation. Over the follow-up period of 12-30 months, no plate and screw
      loosening, hook break and acromion fracture occurred. At 2 months after
      operation, 2 patients had slight pain when moving the shoulder, and the symptom
      disappeared when removing the plate. No re-dislocation was observed in all cases
      after removing the plate at 6-10 months after operation. The function of shoulder
      joint was assessed by Karlsson evaluation standard 1 year after operation, 11
      cases were graded as excellent and 1 case was good. CONCLUSION: For the repair of
      acromioclavicular dislocation, the method of combining clavicular hook plate
      internal fixation with coracoacromial ligament transposition has the advantages
      of minor wound, easy operation, little influence on the function of shoulder
      joints, and reliable restoration of the stability of shoulder joint.

PMID- 19594008
TI  - [Early use of vacuum sealing drainage to repair the wound of the injured in
      Wenchuan earthquake].
AB  - OBJECTIVE: To investigate the method of using vacuum sealing drainage (VSD)
      technique to repair the wound of the injured in Wenchuan earthquake and its
      therapeutic effect. METHODS: From May 12, 2008 to June 12, 2008, 52 injured
      persons (83 wounds) were treated, including 27 males and 25 females aged 11-83
      years old (average 42 years old). There were 22 cases of crush injury, 9 cases of
      contusion and laceration injury, 17 cases of compression injury receiving
      incision decompression of fascia compartment and 4 cases of open amputation. And
      37 wounds were on the leg, 13 wounds on the thigh, 17 wounds on the forearm, 11
      wounds on the upper arm and 5 wounds on the trunk. The wound ranged from 3 cm x 2
      cm to 30 cm x 15 cm, and the time from injury to undergoing VSD treatment was 12
      hours-18 days. After complete debridement, the wound was covered by VSD dressing,
      and antibiotics were given according to the result of drug sensitive test. When
      wound infection was under control and granulation tissues grew well, the method
      of either direct suture or skin grafting or flap transposition was used to repair
      the wounds. RESULTS: In 21 cases (40.4%), wound secretion smear was positive, and
      multiple species of bacteria were detected, such as Staphylococcus aureus,
      Escherichia coli, Proteus and Klebsiella pneumoniae. After initial operation, 7
      injured persons were transferred to the hospital outside of Sichuan province for
      further treatment. VSD treatment was performed on 33 cases (45 wounds) once, 6
      cases (10 wounds) twice, 2 cases (3 wounds) three times and 1 case (1 wound) four
      times, resulting in the control of wound infection and the growth of granulation
      tissue. Then the wounds were repaired by either direct suture or skin grafting or
      flap transposition. Three cases (4 wounds) underwent VSD treatment ten times,
      leading to the control of infection and the stability of condition. CONCLUSION:
      VSD treatment can cover the wound promptly, eliminate contamination, prevent
      secondary infection and benefit late-stage wound repair. During the process of
      treatment, no medical necessity for frequent change of dressing can relieve the
      pain suffered by the injured and decrease the workload of medical stuff, thus
      facilitating the rescue work.

PMID- 19594009
TI  - [Repair of soft tissue defect in finger with modified reverse dorsal digital
      fascia flap].
AB  - OBJECTIVE: To investigate the operative method of repairing soft tissue defect of
      finger with modified reverse dorsal digital fascia flap and its clinical effect
      of preventing and treating venous crisis. METHODS: From February 2005 to March
      2007, 19 cases (22 fingers) with soft tissue defect of finger were treated,
      including 14 males (17 fingers) and 5 females (5 fingers) aged 2-62 years old
      (median 26 years old). There were 8 cases of cutting injury, 6 cases of crush
      injury, 4 cases of avulsion injury, and 1 case of hot crush injury, involving 3
      thumbs, 7 index fingers, 6 middle fingers, 4 ring fingers and 2 little fingers.
      The size of soft tissue defect was 1.5 cm x 0.8 cm-5.5 cm x 1.5 cm, and the time
      from injury to operation was 2-11 hours (average 7 hours). The axis of flaps was
      the line of transverse striation of fingers via dominant artery. The flaps were
      deflected dorsally, as "b" or "d", to cover the wounds. Reverse dorsal digital
      fascia flaps 1.8 cm x 1.0 cm-6.0 cm x 2.0 cm in size were Radopted to repair the
      defects. The donor site underwent skin grafting fixation. RESULTS: All flaps
      survived, without venous acrisis and obvious swollen. The grafted skin in the
      donor site all survived. All patients were followed for 6-18 months (average 11
      months). Postoperatively, color and texture of the grafted flaps were similar to
      that of normal skin, and the pulp of the fingers was normal. The two-point
      discrimination was 8-11 mm, and the activities of interphalangeal joint of all
      injured fingers were normal. CONCLUSION: The modified reverse dorsal digital
      fascia flap is ideal for repairing soft tissues defects of the fingers, and can
      decrease the occurrence of venous crisis.

PMID- 19594010
TI  - [Combined buccal mucosal graft and scrotal flap for reconstruction of urethra in
      primary hypospadias repair].
AB  - OBJECTIVE: To investigate a method of repairing hypospadias by combining buccal
      mucosal graft with scrotal flap and its therapeutic effect. METHODS: From March
      2002 to December 2007, 42 patients with hypospadias underwent primary urethral
      reconstruction using buccal mucosal graft and scrotal flap. The patients ranged
      in age from 18 months to 18 years. There were 21 cases of penoscrotal type, 12
      cases of scrotal type and 9 cases of perineal type. Among them, 8 cases were at
      initial operation, and 34 cases suffered from'the failure of hypospadias repair 6
      19 months (average 10 months) after initial operation. During operation, the
      defect of urethra was 3-7 cm (average 4.2 cm) when the penis was straightened;
      the buccal mucosa (3.0 cm x 1.2 cm-7.0 cm x 1.5 cm) was transplanted to the
      tunica albuginea in the ventral aspect of the penis, and was paired with the
      scrotal flap (3.0 cm x 1.5 cm-7.0 cm x 1.5 cm) to repair urethra. RESULTS: The
      incision of 38 cases healed by first intention, and no complication occurred. At
      7 days after operation, 4 cases had urinary fistula at either coronary sulcus or
      anastomotic stoma, one of which spontaneously closed 2 months after operation and
      the rest 3 recovered by repairing urinary fistula 6 months after operation. All
      patients were followed for 3-48 months (average 18 months). Urination was smooth,
      the reconstructed urethral opening was at the tip of glans peins without
      retraction and with appearance similar to the normal urethral opening. The
      appearance of penis and scrotum was satisfying, and the penis was straightened
      completely. CONCLUSION: Combined buccal mucosal graft and scrotal flap, with
      considerable tissue for urethra tract reconstruction and low incidence rate of
      urethral stricture, is one of the effective methods to repair hypospadias.

PMID- 19594011
TI  - [Clinical analysis of treating 164 cases of tendon and ligament injuries with
      allograft tendon].
AB  - OBJECTIVE: To research the operative method and the clinical efficacy of
      repairing and reconstructing tendon and ligament with allograft tendon. METHODS:
      From September 2000 to May 2007, 164 cases with tendon and ligament injuries were
      treated, including 116 males and 48 females aged 21-47 years old (average 31.5
      years old). There were 126 cases of anterior cruciate ligament injury, 18 cases
      of complete acromioclavicular dislocation, 10 cases of old dislocation of radial
      head, 4 cases of Achilles tendon rupture, 2 cases of tibialis anterior muscle
      rupture, 2 cases of patellar tendon rupture, and 2 cases of rectus femoris
      rupture. Time interval between injury and hospital admission was 4-345 days
      (average 75 days). Allograft tendon 10-26 cm in length with suture anchor or
      absorbable interference screw was used to reconstruct the ligament and tendon.
      RESULTS: All wounds healed by first intention, except one case of rectus femoris
      rupture. All patients were followed for 10-36 months (average 21 months). The
      international knee documentation committee and the Lysholm score of patients with
      anterior cruciate ligament injury 12 months after operation were significantly
      higher than that of before operation (P < 0.01). According to the Lazzcano and
      Karlsson score standard, 13 cases of complete acromioclavicular dislocation at 10
      12 months after operation were graded as excellent and 5 cases were good.
      According to Arner Lindholm score standard, 3 cases of Achilles tendon rupture at
      8-16 months after operation were graded as excellent and 1 case was good. For the
      patients with tibialis anterior muscle rupture, at 10-17 months after operation,
      the limitation of dorsal extension in ankle joint was 5 degrees, and the muscle
      strength in the anterior tibialis muscle was decreased. For the patients with
      patellar tendon rupture, one completely restored the motion range of the knee
      joint 14 months after operation, the other had knee extension limitation of 10
      degrees at 13 months after operation. For the patients with rectus femoris
      rupture, one had 15 degrees of extension limitation at 18 months after operation,
      the other suffered limitation of both extension and genuflex at 12 months after
      operation. According to the Broberg-Morrey score standard, 7 cases with old
      dislocation of radial head were graded as excellent and 3 cases were good at 3-36
      months after operation. CONCLUSION: Allograft tendon is a good material for
      repairing and reconstructing tendon and ligament injuries, but attention should
      be paid to postoperatively early exercise under appropriate protection and early
      management of local rejection.

PMID- 19594012
TI  - [Experimental study of novel injectable nucleus pulposus prostheses implant].
AB  - OBJECTIVE: To explore the histological and the hematological change of rabbits
      after implanting novel injectable artificial nucleus prostheses, and to evaluate
      the biological safety. METHODS: In accordance with Biological Evaluation of
      Medical Devices, materials of polyurethane, silicone rubber and macromolecular
      polyethylene for medical use were made into short column 1 cm in length and 0.3
      cm in diameter. Forty-eight SPF New Zealand white rabbits weighing 2.5-3.0 kg
      were used, and cavity 1 cm in depth was made in the area 2 cm away from the
      spinal midline by separating muscle. Then according to different material being
      implanted, the rabbits were divided into 3 groups (n = 16): Group A,
      polyurethane; group B, silicone rubber; group C, macromolecular polyethylene for
      medical use as negative control. General condition of the rabbits was observed
      after operation. Gross and histology observation were conducted 1, 4, 12 and 26
      weeks after operation. Blood routine, biochemical function and electrolyte assays
      were performed 26 weeks after operation to observe pathological changes of
      organs. Meanwhile, physicochemical properties of the materials were detected, and
      the material in the same batch was used as negative control. RESULTS: All rabbits
      survived until the end of experiment, and all wounds healed by first intention.
      In each group, red swollen muscles were observed 1 week after operation and
      disappeared 4 weeks after operation, connective tissue around the implanted
      materials occurred 12 and 26 weeks after operation. At 26 weeks after operation,
      there were no significant differences among three groups in blood routine,
      biochemical function and electrolyte assays (P > 0.05). Organs had smooth surface
      without ulceration, ecchymosis, obvious swelling, hyperemia or bleeding, and
      nodules. There were no significant differences among three groups in percentage
      weight of each organ (P > 0.05). Histology observation: granulation tissue
      proliferation and inflammatory cell infiltration were observed in each group 1
      week after operation, fibrous capsule formation around the materials and the
      disappearance of inflammatory cell infiltration were evident 4 weeks after
      operation, cyst wall grew over time and achieved stability 12 weeks after
      operation. The inflammatory response and the fiber cyst cavity of groups A and B
      met the standard of GB/T 16175 and were in line with group C. No specific
      pathological changes were discovered in the organs 26 weeks after operation. For
      group A, no significant difference was evident between before and after material
      implantation in terms of weight average molecular weight, number average
      molecular weight, tensile strength at break and elongation at break (P > 0.05).
      For group B, no significant difference was evident between before and after
      material implantation in shore hardness (P > 0.05). CONCLUSION: Novel injectable
      nucleus pulposus prostheses do not damage local tissue and function of organs,
      but provide good biocompatibility and biological safety.

PMID- 19594013
TI  - [Inhibitory effect of curcumin on MMP-2 and MMP-9 expression induced by
      polyethylene wear particles and its mechanism].
AB  - OBJECTIVE: To observe the effect of different dosage of curcumin on expression of
      MMP-2 and MMP-9 in the tissue of cystiform in air-pouch mouse models after the
      injection of polyethylene wear particles, and to investigate its mechanism of
      intervening inflammatory response induced by wear particles. METHODS: Seventy-two
      kunming strain mice were used to establish air-pouch animal models by referring
      to the method of Yang et al. and injecting 3 mL suspension of ultra-high
      molecular weight polyethylene wear particles (concentration 1 x 10(8) cells/mL)
      into dorsal cyst cavity. Then the animals were randomized into 3 groups (n = 24
      per group): group A (control group), 0.6 mL/day normal saline by gavage; group B
      (low-dosage experimental group), 0.6 mL/day curcumin solution at a concentration
      of 1.6 mg/mL by gavage; group C (high-dosage experimental group), 0.6 mL/day
      curcumin solution at a concentration of 3.2 mg/mL by gavage. General condition of
      the animals was observed after operation. The mice were killed 3, 7 and 14 days
      after operation (8 mice per group at a time), the tissue of cystiform was
      harvested to receive gross, histology and immunohistochemistry observation, as
      well as RT-PCR and Western blot detection. RESULTS: All mice survived till the
      end of experiment. White cystiform tissue was evident on the back of mice
      subcutaneously in each group. For diameter of the cyst cavity at each time point,
      group A was obviously greater than groups B and C, and group C was significantly
      less than group B. Microscope observation showed that inflammatory response in
      group A was stronger than that of groups B and C, and group C was obviously less
      than group B at 7 and 14 days. There was a significant difference between groups
      B and C and group A in terms of MMP-2 and MMP-9 expression at 7 and 14 days after
      curcumin delivery (P < 0.05), and no significant differences were evident at 3
      days (P > 0.05). There was no significant difference between group B and group C
      in MMP-2 expression at 7 days after curcumin delivery (P > 0.05), and significant
      difference was evident at 14 days (P < 0.05). There was significant difference
      bewteen group B and group C in MMP-9 expression at 7 and 14 days after curcumin
      delivery (P < 0.05). Nuclear translocation of NF-kappaB P65 was inhibited
      remarkably after curcumin delivery, and there were significant differences among
      three groups at 7 and 14 days (P < 0.05), and no significant differences were
      evident at 3 days (P > 0.05). CONCLUSION: Ultra-high molecular weight
      polyethylene wear particles can stimulate expression of MMP-2 and MMP-9 in
      cystiform tissue. Curcumin can restrain expression of MMP-2 and MMP-9 in
      cystiform tissue of air-pouch animal models, and expression of MMP-2 and MMP-9
      may be regulated by the activation of NF-kappaB.

PMID- 19594014
TI  - [Effect of raloxifene on fracture healing of rabbits].
AB  - OBJECTIVE: To detect the influence of raloxifene (RLX) on fracture healing in
      rabbit. METHODS: Eight healthy New Zealand white rabbits (44 females and 36
      males) weighing 1.9-2.1 kg were used. A 0.5-cm bone defect model in the mid
      diaphysis of the left forelimb radius was established in 72 rabbits, which
      thereafter were divided into 4 groups (n = 18 per group, 10 females and 8 males):
      groups A, B and C received 7.5, 15.0 and 30.0 mg/(kg x d) RLX, respectively, from
      the 2nd to the 50th postoperative day; group D received no further treatment. The
      rest untreated 8 rabbits (4 females and 4 males) served as normal control for
      serum osteocalcin detection. At different postoperative time points, bone mineral
      density detection, X-ray scanning, biomechanics measurement, histology and
      immunohistochemistry observations were conducted; serum estradiol, plasma
      cholesterol, serum osteocalcin and the ratio of uterine weight to body weight
      were detected. RESULTS: The bone mineral density of each group reached a peak 20
      days after operation, showing a significant difference between groups A, B and C
      and group D (P < 0.05), and no significant differences among groups A, B and C (P
      > 0.05). On the 30th and 50th postoperative day, the maximum failure load and the
      maximum displacement of groups A, B and C were greater than those of group D (P <
      0.05), but no significant differences among groups A, B and C were evident (P >
      0.05). On the 7th, 20th and 30th postoperative day, the X-ray score of fracture
      healing of groups A, B and C was greater than group D (P < 0.05); on the 50th
      postoperative day, there was significant difference between groups B and C and
      group D, and between group A and group C (P < 0.05), and no significant
      difference was evident between group B and group C (P > 0.05). The percentage of
      new bone formation in the fractured area of groups A, B and C was greater than
      that of group D on the 30th and 50th postoperative day (P < 0.05). For the type
      II collagen protein secretion in the fractured area, groups B and C were superior
      to group D on the 30th postoperative day (P < 0.05), and there was no significant
      difference between group A and group D (P > 0.05); no significant differences
      among four groups were evident on the 50th postoperative day (P > 0.05). On the
      10th, 30th and 50th postoperative day, the serum osteocalcin of groups A, B, C
      and D was higher than that of normal control (P < 0.05), groups B and C were
      higher than group D (P < 0.05), and there was no significant difference between
      groups A, B and C, and between group A and group D (P > 0.05). For the plasma
      cholesterol, on the 30th postoperative day, no significant change was detected in
      each group (P > 0.05); on the 50th postoperative day, obvious decrease was
      observed in groups A, B and C, showing a significant difference compared with
      group D (P < 0.05). On the 30th and 50th postoperative day, there was significant
      difference between groups B and C and group D in serum estradiol (P < 0.05), and
      no significant differences were evident among other groups (P > 0.05). On the
      30th and 50th postoperative day, the ratio of uterine weight to body weight in
      groups B and C was less than that of group D (P < 0.05), and no significant
      difference was evident between group A and group C (P > 0.05). CONCLUSION: Oral
      administration of 7.5 mg/(kg x d) RLX can promote the fracture healing of rabbit
      radius defect models safely and effectively.

PMID- 19594015
TI  - [Effect of XiangLingGuBao on femoral fracture healing in ovariectomized rats].
AB  - OBJECTIVE: To evaluate the effects of XiangLingGuBao (XLGB) on femoral fracture
      healing in ovariectomized (OVX) rats. METHODS: Forty 12-week-old female SD rats
      weighing (258 +/- 14) g were divided randomly into 4 groups (n = 10 per group):
      group A, sham operation by opening the abdominal cavity; group B, bilateral
      ovariectomy; group C, bilateral ovariectomy, transverse midshaft fracture of the
      right femur with intramedullary nail fixation, and normal saline by gavage; group
      D, bilateral ovariectomy, transverse midshaft fracture of the right femur with
      intramedullary nail fixation, and 250 mg/(kg x d) XLGB by gavage. The weight of
      rabbits in groups A and B was measured 0, 1, 2, 3, 4 and 5 weeks after operation.
      The right femur of each rat was obtained 5 weeks after operation. Total femur
      bone mineral density (tBMD), distal femur bone mineral density (dBMD) and middle
      femur bone mineral density (mBMD) were measured by double energy X-ray
      absorptiometry CR filming, HE staining and immunohistochemistry staining of
      groups C and D were performed. RESULTS: The weight of rats in group B was
      obviously higher than that of group A at 3, 4 and 5 weeks after operation (P <
      0.05), indicating the animal model of postmenopausal osteoporosis was established
      successfully. CR films showed more callus and obscure fracture line in group D,
      while less callus and distinct fracture line in group C. The tBMD and the dBMD of
      group B were far less than that of group A, the mBMD of group D was significantly
      higher than that of group C (P < 0.05), the tBMD and the dBMD of group D were
      higher than that of group C, but no significant difference was evident between
      two groups (P > 0.05). Histology observation showed, when compared with group C,
      most fracture ends in group D reached bone union, and the introduction of
      capillaries was evident in the marrow cavity. Immunohistochemistry staining
      demonstrated that the BMP-2 integrated absorbance (IA) value in groups C and D
      was 2.236 6 +/- 0.181 8 and 3.727 3 +/- 0.874 2, respectively, the VEGF IA value
      in groups C and D was 2.835 5 +/- 0.537 0 and 3.839 6 +/- 0.223 0, respectively,
      indicating there were significant differences between two groups (P < 0.05).
      CONCLUSION: XLGB can obviously promote the femoral fracture healing in OVX rats,
      and speed the transformation of woven bone into lamellar bone, which may rely on
      its role of enhancing expression of BMP-2 and VEGF.

PMID- 19594016
TI  - [Induction of axial vascularization in processed bovine cancellous bone scaffold
      using arteriovenous loop].
AB  - OBJECTIVE: To explore the method of inducing axial vascularization in a processed
      bovine cancellous bone scaffold by using an arteriovenous loop, and to evaluate
      its effect of vascularization. METHODS: Custom-made processed bovine cancellous
      bone discs were processed into cylinder with circular grooves. Thirty male SD
      rats weighing 300-350 g (3-4 months old) were randomly divided into 2 groups (n =
      15 per group): experimental group in which the femoral veins in the groin of rats
      were separated and transplanted to the contralateral femoral artery and vein
      stump, the processed bovine cancellous bone scaffold was inserted into the
      arteriovenous loop, which was placed into the annular groove. Control group, in
      which the blood vessels in the groin of rats were cut, no anastomosis was
      conducted, and the processed bovine cancellous bone scaffold was planted. At 2, 4
      and 8 weeks after operation, gross observation, ink infusion histology
      observation and microvessel bulk density detection were conducted. RESULTS: At
      each postoperative time point, the samples in the experimental group were fresh
      red, the circulation of blood vessels were smooth bidirectionally, while the
      samples in the control group were dark red soft, and flexible. Ink infusion
      histology observation showed the processed bovine cancellous bone scaffold in the
      experimental group had obvious vascularization, the blood vessels tended to be
      mature and integrated into network, and neovascular sprouts originated from
      arteriovenous loop were evident, especially at 8 weeks after operation; while
      there was no vascularization in the control group. At 2, 4 and 8 weeks after
      operation, the bulk density of the microvessels in the experimental group was
      (3.59 +/- 1.84), (16.61 +/- 10.23) and (39.04 +/- 13.46) microm3/microm3,
      respectively, and it was (2.43 +/- 0.97), (6.79 +/- 2.92) and (25.31 +/- 10.98)
      microm3/microm3, respectively, in the control group. Significant differences was
      noted between two groups at 4 and 8 weeks after operation (P < 0.05), and no
      significant difference was evident at 2 weeks after operation (P > 0.05).
      CONCLUSION: Inducing vascularization in a processed bovine cancellous bone using
      an arteriovenous loop is a new strategy of revascularization and may provide
      valuable clues for the preparation of functional artificial bone.

PMID- 19594017
TI  - [Effects of TGF-beta1 neutralizing antibody on collagen production and adhesion
      formation of flexor tendon].
AB  - OBJECTIVE: To investigate the preventive effect of TGF-beta1 neutralizing
      antibody on collagen production and adhesion formation of flexor tendon. METHODS:
      Tendon fibroblasts, epitenon tenocytes, and endotenon tenocytes were obtained
      from 6 New Zealand rabbit flexor tendons. Each cell culture was supplemented with
      1 ng/mL of TGF-beta along with increasing dose of TGF-beta1 neutralizing
      antibody. Col I production was measured by enzyme-linked immunoabsorbent assay
      after 3 days. Eighty-four adult New Zealand White rabbits forepaws underwent
      sharp transection of middle digit flexor digitorum profundus and immediate
      repair. Then the rabbits were divided into three groups: the normal saline (NS
      group, n = 36), 1.0 microg/mL TGF-beta1 neutralizing antibody (1.0 microg/mL TGF
      beta1 group, n = 36) and 2.0 microg/mL TGF-beta1 neutralizing antibody (2.0
      microg/mL TGF-beta1 group, n = 12) were injected in tendon sheath respectively.
      Tendons were harvested at 4 and 8 weeks for biomechanics testing, histological
      evaluation and scanning electron microscope observation. Tendons were harvested
      at 1, 2, 4 and 8 weeks to determine the mRNA expression of TGF-beta1 and Col I by
      in situ hybridization. RESULTS: ELISA exhibed that TGF-beta1 enhanced Col I
      production and the neutralizing antibody significantly inhibited TGF-beta1
      induced Col I production in all 3 cell cultures with a dose-dependent. At 4 and 8
      weeks after operation the gliding excursion of the tendon and the simulated
      active flexion in NS group were less than that of 1.0 microg/mL TGF-beta1 group
      and 2.0 microg/mL TGF-beta1 group. There was significant difference between NS
      group and 1.0 microg/mL TGF-beta1 group, 2.0 microg/mL TGF-beta1 group (P <
      0.05). The tendon anastomosis breaking strength showed no significant differences
      among three groups (P > 0.05). Scanning electron microscope and histological
      observation showed that collagen fibers arranged irregularly in NS group, but
      arranged regularly in 1.0 microg/mL TGF-beta1 group and 2.0 microg/mL TGF-beta1
      group at 4 and 8 weeks after operation. The in situ hybridization results
      revealed that TGF-beta1 and Col I mRNA expression in 1.0 microg/mL TGF-beta1
      group was lower than that in NS group at each time. There was significant
      difference between two groups (P < 0.05). CONCLUSION: TGF-beta1 neutralizing
      antibody can inhibit the function of the TGF-beta1 effectively and prevent
      adhesion formation after the flexor tendon injured and repaired.

PMID- 19594018
TI  - [Comparative study of the effect of different cryoprotectants on desmoglein 1 in
      human skin].
AB  - OBJECTIVE: To compare the effects of two different cryoprotectants on human
      desmoglein 1 (Dsg 1), and to provide experimental basis for the optimization of
      cryoprotectant. METHODS: Five donated thin split-thickness skin grafts were used,
      and the experiment was conducted within 4 hours after skin grafts harvest. The
      skin grafts were divided into 3 groups: group A (n = 2) in which skin grafts were
      immersed in 0.5 mol/L trehalose/DMSO; group B (n = 2) in which skin grafts were
      immersed in DMSO/propanediol; group C (n = 1) in which fresh skin graft received
      no further treatment. Groups A and B were stored in -196 degree C liquid nitrogen
      for 7 and 21 days, respectively, and then underwent experiment.
      Immunohistochemistry staining observation was performed on each group, RT-PCR
      method was used to detect the expression of Dsg 1 in skin. RESULTS: The
      immunohistochemistry staining showed that the protein in groups A and B was
      stained brown-yellow and distributed evenly 7 days after cryopreservation; the
      expression signal of epidermal basal cell was similar to that of group C;
      absorbance (A) value of groups A, B and C was 0.285 +/- 0.006, 0.284 +/- 0.004
      and 0.287 +/- 0.008, respectively, suggesting there was no significant difference
      between groups A and B and group C (P > 0.05). At 21 days after cryopreservation,
      the expression of positive cells in group B decreased; no obvious decrease was
      observed in group A, A value of groups A and B was 0.282 +/- 0.004 and 0.275 +/-
      0.005, respectively, indicating there was a significant difference between group
      B and groups A and C (P < 0.05). RT-PCR detection showed that A value of groups A
      and B at 7 days after cryopreservation was 0.810 +/- 0.012 and 0.803 +/- 0.008,
      respectively; A value of groups A and B at 21 days after cryopreservation was
      0.806 +/- 0.008 and 0.782 +/- 0.013, respectively; and the A value of group C was
      0.814 +/- 0.012, indicating there was significant difference between group B and
      groups A and C at 21 days after cryopreservation (p < 0.05), and no significant
      differences among groups were noted at other time points (P > 0.05). CONCLUSION:
      Trehalose/DMSO is better than traditional cryoprotectant DMSO/propanediol in
      protecting Dsg 1 of human skin.

PMID- 19594019
TI  - [Experimental study of the effect of chitosan/alginate dressings on wound
      immersed in seawater].
AB  - OBJECTIVE: To observe the effect of chitosan/alginate (CTS/ALG) dressings on
      wound immersed in seawater. METHODS: Twenty-five healthy SD rats weighing 250-300
      g were used to establish skin wound model through cutting 1.8 cm circle-shaped
      wound along spine bilaterally. The left side served as experimental group, and
      the right side as control group. The wounds were immersed in the prepared
      artificial seawater for 1 hour, then the experimental group was treated with
      CTS/ALG dressings, while the control group was treated with sterile gauze. Gross
      observation was performed and wound healing time was recorded. At 3, 5, 7, 10 and
      12 days after operation, 2 cm x 2 cm skin tissues including the wounds were
      removed and underwent HE staining and immunohistochemistry staining using
      Envision method. Histological change of wound and expression of EGF receptor
      (EGFR) and bFGF were observed. RESULTS: In the experimental group, wound
      inflammatory response was slight and incrustation shrinked faster, while the
      incrustation in the control group shrinked slowly. The wound healing time of the
      experimental group and the control group was (11.68 +/- 0.57) and (12.51 +/-
      0.54) days, respectively, suggesting there was a significant difference between
      two groups (P < 0.05). In the experimental group, granulation tissue
      proliferation, cell infiltration, collagen tissue proliferation, wound shrinkage
      and epithelization appeared at 3 days after operation; regularly lined collagen
      tissue, complete epithelization and occurrence of skin appendages were observed
      at 10 days after operation; complete wound healing was noted at 12 days after
      operation; while in the control group, at the corresponding time point, late cell
      infiltration and epithelization were observed and granulation tissue with ulcer
      was noted. Immunohistochemistry observation: high expression of bFGF in vascular
      endothelial cells and interstitial fibroblasts and high expression of EGFR in
      vascular endothelial cells were observed in the experimental group at 3 and 5
      days after operation, and their expressions were low at 7, 10 and 12 days after
      operation; while in the control group, there were no or low expression of bFGF
      and EGFR at the same time point. CONCLUSION: CTS/ALG dressings can promote the
      healing of wound immersed in seawater, but its mechanism needs further study.

PMID- 19594020
TI  - [Inhibitory effect of human Col I A1 antisense oligodeoxynucleotide on collagen
      synthesis in hypertrophic scar fibroblasts].
AB  - OBJECTIVE: To investigate the inhibitory effect of Col I A1 antisense
      oligodeoxynucleotide (ASODN) transfection mediated by cationic liposome on Col I
      A1 expression in human hypertrophic scar fibroblasts. METHODS: Scar tissue was
      obtained from volunteer donor. Human hypertrophic scar fibroblasts were cultured
      by tissue block method. The cells at passage 4 were seeded in a 6 well cell
      culture plate at 32.25 x 10(4) cells/well, and then divided into 4 groups: group
      A, liposome and Col I A1 ASODN; group B, Col I A1 ASODN; group C, liposome; group
      D, blank control. At 8 hours, 1, 2, 3 and 4 days after transfection, total RNA of
      the cells were extracted, the expression level of Col I A1 mRNA was detected by
      RT-PCR, the Col I A1 protein in ECM was extracted by pepsin-digestion method, its
      concentration was detected by ELISA method. RESULTS: Agarose gel electrophoresis
      detection of amplified products showed clear bands without occurrence of
      indistinct band, obvious primer dimmer and tailing phenomenon. Relative
      expression level of Col I A1 mRNA: at 8 hours after transfection, group A was
      less than groups B, C and D (P < 0.05), and groups B and C were less than group D
      (P < 0.05), and no significant difference was evident between group B and group C
      (P > 0.05); at 1 day after transfection, groups A and B were less than groups C
      and D (P < 0.05), and there was no significant difference between group A and
      group B, and between group C and group D (P > 0.05 ); at 2 days after
      transfection, there were significant differences among four groups (P < 0.05); at
      3 and 4 days after transfection, group A was less than groups B, C and D (P <
      0.05), group B was less than groups C and D (P < 0.05), and no significant
      difference was evident between group C and group D (P > 0.05). Concentration of
      Col I protein: at 8 hours after transfection, group A was less than groups B, C
      and D (P < 0.05), groups B and C were less than group D (P < 0.05), and no
      significant difference was evident between group B and group C (P > 0.05); at 1
      day after transfection, significant differences were evident among four groups (P
      < 0.05); at 2, 3 and 4 days after transfection, groups A and B were less than
      groups C and D (P < 0.05), and no significant difference was evident between
      group A and group B (P > 0.05). CONCLUSION: Col I A1 ASODN can inhibit mRNA and
      protein expression level of Col I A1. Cationic liposome, as the carrier, can
      enhance the inhibition by facilitating the entry of ASODN into cells and
      introducing ASODN into cell nucleus.

PMID- 19594021
TI  - [Prevention effect of hydroxybutyl chitosan on peritoneal adhesion in rats].
AB  - OBJECTIVE: To explore the effect of hydroxybutyl chitosan on the prevention of
      postoperative peritoneal adhesion in rats. METHODS: Ninety SD rats (half males
      and half females) weighing 250-280 g underwent laparotomy with subsequent cecal
      wall abrasion and peritoneal adhesion. Rats were randomized into 3 groups (n = 30
      per group): group A, injection of 2 mL hydroxybutyl chitosan solution (2%); group
      B, injection of 2 mL sodium hyaluronate solution (2%); group C, the abdomen of
      rat was exposed for 30 seconds and served as control group. The general condition
      of the rats was observed after operation. The rats were killed 2 and 4 weeks
      after operation, 15 rats per group at a time, to undergo gross and histology
      observation. The degree of adhesion was evaluated by double-blind method. The
      microstructure of injured electroscope cecal wall in groups A and C was observed
      with transmission electroscope 4 weeks after operation. RESULTS: All rats
      survived till the end of experiment. At 2 weeks after operation, the adhesion and
      the hyperplasia of fibrous connective tissue and collagen in groups A and B were
      slight while the adhesion in group C was serious with severe hyperplasia of
      fibrous connective tissue. According to the measurement classification by Nair
      histological grading, the difference between groups A and B and group C was
      significant (P < 0.05), while no significant difference was evident between group
      A and group B (P > 0.05). At 4 weeks after operation, the adhesion in group A was
      mild, and the hyperplasia of fibrous connective tissue and collagen were slight;
      the adhesion and the hyperplasia of fibrous connective tissue and collagen in
      group C were serious. The levels of group B were between group A and group C. The
      differences among three groups were significant (P < 0.05). Transmission
      electroscope showed inactive fibroblasts and loose thin collagen fibers in group
      A, and active fibroblasts and closely collagen fibers arranged in a disorderly
      manner in group C. CONCLUSION: Hydroxybutyl chitosan can decrease the hyperplasia
      of fibrous connective tissue and inhibit the activity of fibroblasts
      significantly, and has a long-term role of preventing peritoneal adhesion.

PMID- 19594022
TI  - [Effect of propofol on spinal excitatory amino acid accumulation].
AB  - OBJECTIVE: To investigate the protective effect of propofol on
      ischemia/reperfusion induced spinal cord injury in rabbits and its influence on
      excitatory amino acid (EAA). METHODS: Sixty New Zealand white rabbits weighing
      2.0-2.5 kg, half males and half females, were selected. The infrarenal
      circumaortic clamping model was used. And 6 mL/kg different fluids were
      continuously infused through a catheter into the aorta distal to the clamping
      site at a speed of 12 mL/(kg x h) during the 30 minutes ischemia period.
      According to the different infusing liquids, the rabbits were randomized into 6
      groups (n = 10 per group): group A, normal saline; group B, 10% intralipid; group
      C, propofol 30 mg/kg; group D, propofol 40 mg/kg; group E, propofol 50 mg/kg;
      group F, propofol 60 mg/kg. At 0, 6, 24, and 48 hours after reperfusion,
      neurologic outcomes were scored on a Tarlov scale system. At 48 hours after
      reperfusion, the number of normal neurons in the anterior spinal cord was
      counted, and concentration of EAA in the lumbar spinal cord was measured by high
      performance liquid chromatography. RESULTS: The neuroethological score was better
      in groups C, D, E and F than that of groups A and B (P < 0.05), the score of
      group E was the highest (P < 0.05), and there was no significant difference
      between group A and group B (P > 0.05). The number of normal neurons in the
      anterior spinal cord of groups C, D, E and F was greater than that of groups A
      and B (P < 0.05), and group E was greater than groups C, D and F (P < 0.05). The
      concentration of EAA in groups A, B, C, D, E and F was greater than that of
      normal tissue, the group E was the lowest (P < 0.05), the groups A and B were the
      highest (P < 0.05), and there was no significant difference between group A and
      group B (P > 0.05). Concentrations of glutamate and aspartic acid were negatively
      correlated to normal neuron numbers in the anterior spinal cord and
      neuroethological scores 48 hours after reperfusion, and the corresponding
      correlation coefficient was -0.613, -0.536, -0.874 and -0.813, respectively (P <
      0.01). CONCLUSION: Propofol can significantly inhibit the accumulation of EAA in
      spinal cord and provide a protective effect against the ischemia/reperfusion
      injury induced spinal cord in rabbits.

PMID- 19594023
TI  - [Cytobiological effect of adipose-derived stem cells treated with insulin on
      HaCaT cells].
AB  - OBJECTIVE: To isolate and culture adipose-derived stem cells (ADSCs), and to
      study the effects of the conditioned medium of ADSCs (ADSC-CM) treated with
      insulin on HaCaT cells. METHODS: ADSCs were isolated from adipose tissue donated
      by the patient receiving abdominal surgery and were cultured. The concentration
      of ADSCs at passage 3 was adjusted to 5 x 10(4) cells/mL. The cells were divided
      into 2 groups: group A in which the cells were incubated in 1 x 10(-7) mol/L
      insulin for 3 days, and group B in which the cells were not treated with insulin.
      ADSC-CM in each group was collected 3 days after culture, then levels of VEGF and
      hepatocyte growth factor (HGF). HaCaT cells were cultured and the cells at
      passage 4 were divided into 4 groups: group A1, 0.5 mL 2% FBS and 0.5 mL ADSC-CM
      from group A; group B1, 0.5 mL 2% FBS and 0.5 mL ADSC-CM from group B; group C1,
      1 mL 2% FBS of 1 x 10(-7) mol/L insulin; group D1, 1 mL 2% FBS. Proliferation of
      HaCaT cells was detected by MTT method 3 days after culture, apoptosis rate of
      HaCaT cells was measured by Annexin V-FITC double staining 12 hours after
      culture, and the migration ability was measured by in vitro wound-healing assay
      0, 12, 24, 36 and 48 hours after culture. RESULTS: The level of VEGF in groups A
      and B was (643.28 +/- 63.57) and (286.52 +/- 46.68) pg/mL, respectively, and the
      level of HGF in groups A and B was (929.95 +/- 67.52) and (576.61 +/- 84.29)
      pg/mL, respectively, suggesting differences were significant between two groups
      (P < 0.05). Cell proliferation detection showed the absorbance value of HaCaT
      cells in group A1, B1, C1 and D1 was 0.881 +/- 0.039, 0.804 +/- 0.041, 0.663 +/-
      0.027 and 0.652 +/- 0.042, respectively, suggesting there was significant
      difference between groups A1 and B1 and groups C1 and D1 (P < 0.01), group A1 was
      significantly higher than group B1 (P < 0.05). The apoptosis rate of HaCaT cells
      in groups A1, B1, C1 and D1 was 5.23% +/- 1.98%, 8.82% +/- 2.59%, 31.70% +/-
      8.85% and 29.60% +/- 8.41%, respectively, indicating there was significant
      difference between groups A1 and B1 and groups C1 and D1 (P < 0.05), group B1 was
      significantly higher than group A1 (P < 0.05). The migration distance of HaCaT
      cells in groups A1, B1, C1 and D1 at 36 hours was (0.184 6 +/- 0.019 2), (0.159 8
      +/- 0.029 4), (0.059 2 +/- 0.017 6) and (0.058 2 +/- 0.012 3) mm, respectively,
      whereas at 48 hours, it was (0.231 8 +/- 0.1740), (0.205 1 +/- 0.012 1), (0.079 2
      +/- 0.008 1) and (0.078 4 +/- 0.011 7) mm, respectively, suggesting there were
      significant differences between groups A1 and B1 and groups C1 and D1 at 36 and
      48 hours (P < 0.01), group A1 was significantly higher than group B1 (P < 0.05)
      at 36 and 48 hours, no significant difference was evident at other time points (P
      > 0.05). CONCLUSION: ADSCs treated with insulin can significantly promote the
      proliferation and the migration of HaCaT cells and inhibit their apoptosis.

PMID- 19594024
TI  - [Experimental research of the promotion effect of autogeneic PRP on osteogenic
      differentiation of human adipose-derived stem cells in vitro].
AB  - OBJECTIVE: To study the effect of autogeneic PRP on proliferation and
      osteogenetic differentiation of human adipose-derived stem cells (ADSCs) in
      vitro. METHODS: ADSCs were isolated from adipose tissue obtained from donor
      undergoing liposuction and were cultured, and growth condition of the cells was
      observed by inverted microscope. ADSCs at passage 3 were cultured in adipogenic
      or chondrogenic medium and underwent identification, immunofluorescence staining
      observations for CD29 and CD44 were performed. ADSCs at passage 3 were divided
      into 2 groups: PRP group cultured by osteogenic induction culture medium
      containing 10 mL/L PRP, and control group cultured by osteogenic induction
      culture medium without PRP. Then growth condition of the cells was observed by
      inverted microscope. MTT method was used to observe cell proliferation activity
      1, 2, 3, 4 and 5 days after culture. ALP activity detection was conducted 7, 14,
      21 and 28 days after culture. ALP staining was performed on PRP group 7 and 14
      days after culture. Alizarin red staining was performed on PRP group 14 days
      after culture to detect the formation of calcium nodule. RESULTS: Under the
      inverted microscope, most ADSCs at passage 3 were spindle-shaped and the doubling
      time was about 35 hours. Adipogenic and chondrogenic differentiation were
      confirmed, and the cells were positive for CD29 and CD44 immunofluorescence
      staining. MTT method revealed the absorbance value of PRP group at 1, 2, 3, 4 and
      5 days was 0.137 +/- 0.015, 0.219 +/- 0.023, 0.367 +/- 0.031, 0.586 +/- 0.039 and
      0.948 +/- 0.046, respectively, and in the control group, it was 0.081 +/- 0.009,
      0.115 +/- 0.012, 0.162 +/- 0.017, 0.242 +/- 0.025 and 0.356 +/- 0.032,
      respectively, suggesting there were significant differences between two groups (P
      < 0.01). At 7 days after osteogenic induction, PRP group was positive for ALP
      staining, grey-black cell plasma and black precipitate were evident; the positive
      cells increased 14 days after osteogenic induction. ALP activity detection
      demonstrated the cell activity value of PRP group at 7, 14, 21 and 28 days was
      23.96 +/- 2.05, 41.26 +/- 3.38, 38.12 +/- 3.03 and 35.89 +/- 2.24, respectively,
      while in the control group, it was 17.83 +/- 1.62, 26.64 +/- 2.37, 23.85 +/- 1.99
      and 20.78 +/- 1.81, respectively, indicating there were significant differences
      between two groups (P < 0.01). At 14 days after osteogenic induction, Alizarin
      red staining showed the formation of calcium nodule in PRP group. CONCLUSION:
      Autogeneic PRP can improve the proliferation of human ADSCs and induce their
      osteogenic differentiation in vitro, providing a new source of seed cells for
      bone tissue engineering.

PMID- 19594025
TI  - [In vitro study on multiple differentiation potential of swine synovium-derived
      MSCs].
AB  - OBJECTIVE: To study the method of isolating and culturing synovium-derived MSCs
      (SMSCs), and to investigate its multiple differentiation potential in vitro.
      METHODS: Three 2-month-old Changfeng hybrid swines weighing 8-10 kg (male and
      female) were used. SMSCs were harvested from the synovium of swine knee joints
      and cultured in vitro. When the SMSCs at passage 3 reached confluence, basic
      culture medium was removed, and the multiple differentiation potential of SMSCs
      was demonstrated in specific induction media (experimental group). The cells at
      passage 3 cultured with basic culture medium served as control group. After 21
      days of chondrogenic differentiation, the cells underwent toluidine blue
      staining, immunohistochemistry staining and real-time fluorescence quantitative
      PCR detection. After 10 and 21 days of osteogenic differentiation, the cells
      underwent ALP staining and Alizarin red staining, respectively. After 21 days of
      adipogenic differentiation, the cells underwent Oil red O staining. RESULTS:
      SMSCs displayed long and thin or polygonal morphology 24 hours after culture.
      They proliferated fast 48 hours after culture and presented large number of
      spindle-shaped cells with few globular cells 72 hours after culture. For the
      experimental group 21 days after chondrogenic induction, the cells were positive
      for toluidine blue staining with the formation of Aggrecan outside the cells; the
      immunohistochemistry staining revealed the expression of Col II; the real-time
      fluorescence quantitative PCR detection showed that the expressions of Col II A1,
      Aggrecan and SOX9 mRNA of the experimental group were greater than that of
      control group (P < 0.05). The cells were positive for ALP staining 10 days after
      osteogenic induction, and positive for Alizarin red staining 21 days after
      osteogenic induction, with the formation of calcium nodules. Oil red O staining
      displayed the formation of lipid droplets inside the cells 21 days after
      adipogenic induction. For the control group, the results of all the staining
      assays were negative except the ALP staining presenting with slight positive
      result. CONCLUSION: SMSCs can be isolated from knee joint of swine and
      proliferate and differentiate into osteogenic, adipogenic and chondrogenic cells
      in vitro. SMSCs may be a promising source of seed cells for tissue engineering.

PMID- 19594026
TI  - [Effect of Wnt-1 on the process of inducing neural stem cells into neurons by all
      trans-retinoic acid in vitro].
AB  - OBJECTIVE: To explore the expression of Wnt-1 during the process of inducing
      neural stem cells (NSCs) into neurons by using all-trans-retinoic acid (ATRA) in
      vitro and the effect of Wnt-1 on NSCs differentiation. METHODS: NSCs isolated
      from cerebral cortex of SD rat embryo (12-16 days' gestation) were cultured. The
      concentration of cells at passage 3 were adjusted to 1 x 10(6) cells /mL and
      treated with ATRA at 0.5, 1.0, 5.0 and 10.0 micromol/L, respectively.
      Differentiation ratio of NSCs into neurons in each group was detected by double
      labelling immunofluorescence technique and flow cytometry, and 1.0 micromol/L was
      selected as the best concentration for ATRA to promote NSCs differentiation. In
      experimental group, NSCs at passage 3 were cultured with ATRA at 1.0 micromol/L
      in vitro, and expression of Wnt-1 was detected by immunocytochemistry staining,
      real-time fluorescent quantitive PCR and Western blot at 3, 5, 7 and 9 days after
      culture, respectively. The cells at passage 3 receiving no ATRA served as control
      group. RESULTS: Immunocytochemistry staining: in the control group, there was
      little Wnt-1 protein expression; in the experimental group, peak expression of
      Wnt-1 and numerous positive cells occurred at 3 days after culture, the positive
      expression of Wnt-1 was still evident at 5 days after culture, and there was
      significant difference between two groups in integrated absorbance (IA) value at
      3 and 5 days after culture(P < 0.05), obvious decrease of positive expression of
      Wnt-1 was evident, and no significant difference was evident between two groups
      in IA value at 7 and 9 days (P > 0.05). Real-time fluorescence quantitative PCR:
      the relative expression of Wnt-1 mRNA in the control group was 0.021 7 +/- 0.072
      1; the relative expression of Wnt-1 mRNA in the experimental group at 3, 5, 7 and
      9 days was 0.512 2 +/- 0.280 0, 0.216 4 +/- 0.887 0, 0.038 5 +/- 0.299 4 and
      0.035 5 +/- 0.309 5, respectively, indicating the value decreased over time, and
      there were significant difference between two groups at 3 and 5 days (P < 0.05),
      and no significant difference at 7 and 9 days (P > 0.05) . Western blot
      detection: specific and visible staining band was noted; in the control group,
      Wnt-1 protein expression was 0.005 1 +/- 0.558 3; in the experimental group, Wnt
      1 protein expression at 3, 5, 7 and 9 days was 0.451 7 +/- 0.071 3, 0.311 7 +/-
      0.080 5, 0.007 3 +/- 0.052 7 and 0.004 7 +/- 0.9314, respectively, suggesting the
      value decreased over time; there were significant differences between two groups
      at 3 and 5 days (P < 0.05), and no significant differences at 7 and 9 days (P >
      0.05). CONCLUSION: With the induction of ATRA at 1.0 mmicromol/L, Wnt-1 and NSCs
      differentiation in early stage are positively correlated. Its possible mechanism
      may rely on the activation of such signals as classic Wnt-1 signal pathway,
      indicating Wnt-1 relates to the differentiation of NSCs into neurons.

PMID- 19594027
TI  - [Cytocompatibility study of Arg-Gly-Asp-recombinant spider silk protein/poly
      vinyl alcohol scaffold].
AB  - OBJECTIVE: To evaluate the cytocompatibility of Arg-Gly-Asp-recombinant spider
      silk protein (pNSR16)/ poly vinyl alcohol (PVA) through in vitro cytotoxicity
      experiment and cell-material co-culture experiment. METHODS: pNSR16/PVA scaffold
      and its extraction were prepared by using solvent casting/particulate leaching
      method, and NIH-3T3 cells were cultivated with the extraction in vitro. The
      cytotoxicity of scaffold was analyzed using MTT assay 1, 3 and 5 days after
      culture. Scanning electron microscope and HE staining observation were conducted
      2, 4 and 6 days after culturing NIH-3T3 cells on the pNSR16/PVA scaffold.
      Immunohistochemistry detection was performed 6 days after co-culture. Adhesion,
      growth and expression of the cells on the scaffold were observed. RESULTS: The
      cytotoxicity of pNSR16/PVA scaffold was in grade 0. Scanning electron microscope
      observation: the cells covered the surface of the scaffold and were arranged in a
      directional manner 4 days after co-culture. HE staining: the cells adhered to and
      grew on the surface of scaffold, and migrated into the scaffold with the increase
      of culture duration. Immunohistochemistry detection: bFGF was secreted by NIH-3T3
      cells, and the cells differentiated normally. CONCLUSION: pNSR16/PVA scaffold has
      a satisfactory cytocompatibility and may be an ideal tissue engineered scaffold
      material.

PMID- 19594028
TI  - [Repair effect of BMSCs on digestive tract injury].
AB  - OBJECTIVE: To investigate the effect of BMSCs on the repair of digestive tract
      injury and its mechanisms. METHODS: Recent literature on the effect of BMSCs on
      the repair of digestive tract injury was reviewed. RESULTS: BMSCs had the potency
      of self-replication, proliferation and multipotential differentiation, which
      played an important role in the repair of digestive tract injury. The probable
      mechanisms included: BMSCs' ability of migrating to the injured tissue and
      inhibiting the host immune response; BMSCs' dedifferentiation and
      redifferentiation; BMSCs' direct differentiation into the epithelial cells or the
      stem cells of digestive tract; BMSCs' fusion with the stem cells or the mature
      epithelial cells of digestive tract; BMSCs' participation in the reconstruction
      of injured microenvironment. CONCLUSION: BMSCs participates in the repair of
      digestive tract injury and has a bright future in the treatment of digestive
      system disease.

PMID- 19594029
TI  - [Research progress of hypoxia inducible factor 1alpha in hypoxic-ischemic
      injury].
AB  - OBJECTIVE: To review the role of hypoxia inducible factor 1alpha (HIF-1alpha) in
      hypoxic-ischemic injury and its repair, and to analyze the possible mechanisms.
      METHODS: Recent literature on HIF-1alpha and its role in hypoxic-ischemic injury
      was reviewed and analyzed. RESULTS: HIF-1alpha was involved in the hypoxic
      ischemic injury of various organs or tissues and their repair processes.
      CONCLUSION: HIF-1alpha has a potential to treat common clinical hypoxic-ischemic
      injuries and has a promising future for application.

PMID- 19594030
TI  - [Progress in the treatment of chronic Achilles tendon rupture].
AB  - OBJECTIVE: To review the progress in the treatment of chronic Achilles tendon
      rupture. METHODS: Recent literature on the treatment of chronic Achilles tendon
      rupture was reviewed. RESULTS: The choice of operative method for the repair of
      chronic Achilles tendon rupture depended primarily on the length of tendon
      defect, the atrophic condition of triceps surae muscle, and the age and the
      sportive level of patient. CONCLUSION: Most chronic Achilles tendon ruptures
      should be treated operatively to reach good functional recovery, and tissue
      engineering provides a promising future for tendon defect repair.

PMID- 19594031
TI  - [Weighting the pros and cons of joint replacement: the comprehend of an old joint
      surgeon].

PMID- 19594032
TI  - [Total hip replacement for the treatment of Crowe IV congenital hip dislocation
      using small acetabular components combined with medial protrusio technique].
AB  - OBJECTIVE: To summarize the surgical technique and the clinical results of small
      acetabular components combined with medial protrusio technique in primary total
      hip arthroplasty (THA) for the treatment of Crowe type IV congenital hip
      dislocation (CHD). METHODS: From January 2000 to December 2005, total 14 patients
      (16 hips) of Crowe type IV CHD underwent cementless THA (12 unilateral, 2
      bilateral) with this new technique. There were 2 males and 12 females with an
      average age of 49 years (range, 38 to 75 years). The indications for surgery was
      severe hip pain and leg length discrepancy with difficulty in walking and
      activating. Cup design: Duraloc (Depuy, Warsaw, USA) in 10 hips, Pressfit S II
      (LINK, Germany) in 6 hips. The outside diameter of the cup was 42 to 44 mm; and
      the thickness of the polyethylene liner was 6 to 7 mm. Total hip replacement were
      performed with the medial protrusion technique to stabilize the fit of a
      hemispherical metal cup in the acetabulum. The hip functions were evaluated by
      Harris hip score. The muscle strength of the gluteus medius and gait were
      respectively evaluated in accordance with the standards of five and four classes.
      RESULTS: The X-ray showed that the average superolateral bone coverage in these
      16 hips (none of which had bone graft) was more than 98 percent. The cup was an
      average of (5.8 +/- 1.2) mm medial and (6.2 +/- 1.7) mm superior to the Ranawat
      triangle. The follow-up period ranged from 3 to 9 years. The Harris hip score
      improved from 25 to 32 preoperatively to 90 to 98 1 year postoperatively. X-ray
      showed that perforated area of the medial acetabulum were repaired with healed
      bone mud 4 to 8 months after operation. The rate of linear wear of the
      polyethylene liner averaged (0.10 +/- 0.03) mm each year. Until now, no aseptic
      loosening or osteolysis was identified around the acetabulum components, no
      acetabular components were revised for loosening or other reasons. CONCLUSION:
      Small acetabular components combined with medial protrusio technique is a simple,
      reliable and flexible surgical technique. Early and mid-term result in total hip
      arthroplasty with this technique for the treatment of Crowe type IV CHD is
      satisfactory.

PMID- 19594033
TI  - [Preliminary clinical outcome of domestic posterior-stabilized total knee
      arthroplasty].
AB  - OBJECTIVE: Total knee arthroplasty (TKA) has been widely used in China. More and
      more attentions are paid to the development of knee prosthesis that fit for the
      anatomy of Chinese knee. This study is to summarize the surgical techniques and
      clinical outcome of domestic posterior-stabilized total knee arthroplasty.
      METHODS: Fifty-one patients including 19 males and 32 females underwent TKA by
      using TC-Dynamic from Jan. 2003 to Dec. 2004 were reviewed. The average age at
      the time of operation was (76.4 +/- 4.1) years (range, 71 to 84 years). Thirty
      seven patients suffered from osteoarthritis and 14 patients were rheumatism
      arthritis. The courses of the disease ranged from 5 to 40 years and the symptoms
      were pain and limitation of motion. The knee rating score system (HSS) as well as
      X-rays of the lower extremity was used to evaluate the clinical results. RESULTS:
      All patients were followed up at the 3rd month after TKA and the duration of
      follow-up of 32 patients ranged from 48 to 61 months. The HSS scores before TKA
      was (53.3 +/- 6.7) (40 to 59) points. At the 3rd month and 48th month of follow
      up, the HSS scores were (86.1 +/- 7.7) (63 to 95) and (83.5 +/- 8.1) (60 to 95)
      points respectively. The stress X-rays showed preoperative varus deformities from
      9 degrees to 30 degrees with the average of (21.0 +/- 5.8) degrees and normal
      alignment of the lower extremities postoperative. There were no complications
      related to TC-Dynamic prosthesis and other complications such as infection,
      prosthetic loosening and dislocation of patella. CONCLUSION: There is a good mid
      term clinical result of TC-Dynamic knee system, which is designed according to
      anatomical characteristic of Chinese knee joint. More attention should be paid to
      this knee system about the long term follow-up.

PMID- 19594034
TI  - [Clinical analysis and prevention from coating shedding of uncemented hip
      prosthesis].
AB  - OBJECTIVE: The long-term biological effects of HA-coated prostheses remain
      uncertain. The purpose of the study is to analyze the reasons of coating shedding
      of uncemented hip prothesis, so as to provide evidences for the preventions and
      treatment. METHODS: From 2002.10 to 2009.2, 5 patients with coating shedding of
      uncemented hip prosthesis were treated with kip revision operation. Among the
      patients, 3 patients were male and 2 patients were female, ranging in age from 55
      to 68 years. The hip prosthesis were taken out in the operation and the cause of
      coating shedding was analyzed. Another ten normal prosthesis taken out from the
      revision operation were used as the control group. The histomorphology and
      microarchitecture of hip prosthesis were observed. The micrometer caliper and
      vickers hardness test were used to measure the thickness and hardness. The
      interface shearing force was measured by push-out test. The function of hip joint
      was evaluated by Harris score. RESULTS: There were difference between control and
      experience groups in his tomorphology observation. In the 2 patients with HA
      coated shedding, the thickness of coating were 112 microm and 138 microm
      respectively; Vickers hardness were 5,843 Hv and 4,524 Hv respectively; and the
      shear strength were 12.4 MPa and 11.6 MPa respectively. In the 3 patients with Ti
      coated shedding, the Harris scores were 82, 88 and 87 respectively. CONCLUSION:
      There are many reasons of coating shedding of uncemented hip prosthesis. But most
      reasons have relationship with the quality of hip prosthesis. Nowadays, there are
      many methods to enhance the binding strength between the coating and prosthesis,
      and to prevent the early coating shedding.

PMID- 19594035
TI  - [Clinical effects of comprehensive rehabilitation after minimally invasive total
      hip arthroplasty].
AB  - OBJECTIVE: To explore clinical effects of comprehensive rehabilitation therapy
      for function restore of hip joint after minimally invasive total hip
      arthroplasty. METHODS: From March 2006 to February 2008, 100 patients were
      randomly divided into the treatment group and the control group. Fifty patients
      in the treatment group, including 21 males and 29 females, ranging in age from 56
      to 78 years, with an average of (67.2 +/- 11.0) years. Fifty patients in the
      control group, including 26 males and 24 females, ranging in age from 54 to 79
      years, with an average of (65.5 +/- 11.5) years. The course of disease of the two
      groups were 10 to 15 years. The comprehensive rehabilitations such as joint range
      of motion, the activities of daily living and restoring muscle strength were
      performed step-by-step in the treatment group under the guidance of the therapist
      at the 2nd day after hip arthroplasty. Above rehabilitations were not performed
      in the control group. The postoperative functional recovery of hip joint, the
      Harris scores and X-ray were analyzed and compared between the two groups.
      RESULTS: All the patients were followed and the duration averaged 13 months (12
      to 14 months). The therapeutic effects of the two groups had statistical
      differences, Zc =12.72, P<0.001. In the treatment group, the average Harris score
      was (94.50 +/- 29.87), 32 patients got an excellent result, 12 good, 4 poor and 2
      bad. While in the control group, above data were (63.50 +/- 19.97), 12, 15, 7 and
      16 respectively. The therapeutic effects of treatment group were better than
      those of control group. The X-ray showed that there were no hip prosthesis
      loosening, femoral neck fractures and other complications. CONCLUSION: The early
      comprehensive rehabilitation after minimally invasive total hip replacement is
      the key to decrease postoperative complications and to decide the success or
      failure of surgery.

PMID- 19594036
TI  - [Study on how much sterile saline should be used for efficient lavage during
      total knee arthroplasty].
AB  - OBJECTIVE: To investigate the volume of pulse lavage sufficient for removal of
      intraoperative bone and polymethyl methacrylate (PMMA) particles. METHODS: From
      2007.11 to 2008.11, 18 patients with osteoarthritis underwent cemented TKA. Among
      the patients, 6 patients were male and 12 patients were female, ranging in age
      from 54 to 77 years, with an average of 61.5 years. The course of disease ranged
      from 3 to 9 years, mean 6.7 years. Pulse lavage with 1 L of sterile saline was
      performed for 8 times using a pulsatile irrigator after prothesis fixed. During
      pulse lavage, aspirated fluid was collected in a 1 L aliquot, and the weight of
      bone and PMMA particles in each fluid were measured. RESULTS: The weight of
      particles peaked in the first 1 L lavage fluid and gradually decreased until the
      8th lavage fluid. Significant differences were found between the first vs second,
      second vs third, and third vs fourth lavage. However, no significant differences
      were found beyond the fourth lavage. CONCLUSION: The results of this study
      indicates that 4 L of pulse lavage is effective for removing the bone and PMMA
      particles during cemented TKA.

PMID- 19594037
TI  - [Swanson double-stem silicone implant arthroplasty in the treatment of Freiberg
      disease].
AB  - OBJECTIVE: To observe the short-term results of Swanson double-stem silicone
      implant arthroplasty in the treatment of late stage Freiberg disease. METHODS:
      From July 2006 to December 2007, Swanson double-stem silicone implant
      arthroplasty was performed on 13 patients, 11 male (1 foot) and 12 females (17
      feet), suffering from late stage Freiberg diseases. All the cases were the second
      metatarsophalangeal joints. According to the Smillie classification, 11 feet
      present with grade 4 osteonecrosis, 7 feet with grade 5. The AOFAS scoring system
      was used for clinical assessment. All the patients were followed up for an
      average of 11.3 months (3 to 17 months). RESULTS: The mean preoperative and
      postoperative AOFAS scores were (50.06 +/- 9.59) and (77.50 +/- 4.99),
      respectively (P<0.05). The complaint of pain with joint motion was decreased in
      all patients. The postoperative passive range of motion of joints improved
      significantly. CONCLUSION: Swanson double-stem silicone implant arthroplasty
      yields satisfied short-term results in late stage Freiberg disease, which is
      effective to improve range of motion and relieve pain of joint.

PMID- 19594038
TI  - [The monitoring and analysis of arthroplasty related infection].
AB  - OBJECTIVE: To monitor and analyze the arthroplasty related infection situations
      of Drum Tower Hospital, so as to provide evidences for the prevention of
      infection after arthroplasty. METHODS: Monitoring of infection situations of nine
      arthroplasty operations were carried out from July to August in 2008. Five
      sampling methods were used to monitor the air of the 30 m2 surgery for 4 times.
      Through the cotton swab sampling, hands of 14 surgeons and 76 samples of surgical
      instruments (forceps, surgical scissors, retractors) were collected and then for
      bacterial culture. RESULTS: The average amount of the total number of free
      floating bacteria in our surgery was 88.2 cfu/m3. For the germiculture, 8 samples
      of hand detections were positive; 11 samples of surgical instruments including
      those used and unused and exposed at different times were positive. CONCLUSION:
      In the surgery of arthroplasty, all operation personnels should protect the air
      cleanliness degree, obey the surgical hand-washing rules and diminish the exposed
      time of aseptic table.

PMID- 19594039
TI  - [Study on short-term effects of ankle replacement for the treatment of hemophilic
      arthritis].
AB  - OBJECTIVE: To evaluate the short-term effects of ankle joint replacement for the
      patients with hemophilic arthritis. To find out the main points for improving the
      joint function and the patients' life quality. To accumulate more experience for
      clinical treatment. METHODS: The Kofoed evaluation system and the AOFAS
      evaluation system were used to follow-up 6 hemophilic patients with ankle
      arthritis (6 males, ranging in age from 23 to 57 years, with an average of 41.2
      years), who were treated with ankle joint replacement from 2004.7 to 2007.7. The
      scores before operation, and the 6th,12th months after operation were compared.
      RESULTS: The Kofoed evaluation system showed the joint replacement significantly
      improved the scores for relieving pain, joint function, range of motion and the
      total score (P<0.05). Except the score for relieving pain, the other three also
      had significant differences between the 6th month and the 12th month after the
      operation (P<0.05). Compared with each details of the joint function, there was
      significant improvement before and after the operation (P<0.05). The ankle got
      more extended range of motion in the 12th month after operation than the 6th
      month (P<0.05). The AOFAS evaluation system showed the joint replacement
      significantly improved the scores for relieving pain, joint function, X-ray
      measurement and the total score (P<0.05). There was no differences between the
      6th month after operation and the 12th month in the results for relieving pain
      and the X-ray measurement (P>0.05). However, the joint function and the total
      score had significant differences (P<0.05). Compared with each details of the
      joint function, there was also significant improvement before and after the
      operation (P< 0.05), and the walk distance, as well as the joint flexion and
      extension activities, had differences between the 6th month and the 12th month
      after the operation. Both of the two evaluation system showed the operation could
      get good curative effects (P< 0.05), and the artificial joint could constantly be
      in good condition from the 6th month to the 12th month after operation (P> 0.05).
      CONCLUSION: In this short-term observation, the joint replacement can
      significantly improve the life quality for the hemophilic patients with ankle
      arthritis.

PMID- 19594040
TI  - [Hip resurfacing arthroplasty in patients with ankylosing spondylitis].
AB  - OBJECTIVE: To study the short-term results of metal on metal hip resurfacing
      arthroplasty (HRA) for the treatment of patients with ankylosing spondylitis
      (AS), to explore the indications and technology of this surgery. METHODS: From
      February 2006 to April 2008, 11 patients (15 hips) with ankylosing spondylitis
      were treated with metal on metal total hip resurfacing arthroplasty. Among them,
      9 patients were male, and 2 patients were female, with an average age of 32.5
      years (ranged from 16 to 53 years). The comparative study on preoperative and
      postoperative pain, range of motion, correction of deformity and function
      evaluation were performed. The preoperative and postoperative Harris scores were
      compared and the feasibility and technical difficulty were analyzed. RESULTS: Ten
      patients were followed up for an average period of 16.2 months (ranged from 8 to
      34 months) and 1 patient was lost. Pain disappeared in 10 patients. There were no
      heterotopic ossification, no femoral neck fracture, no dislocation, no infection
      and no revision in all patients. From preoperation to present, the mean flexion
      angle of hip was improved from preoperative 0 degrees to 75 degrees to
      postoperative 35 degrees to 105 degrees; the mean abducting angle of hip was
      improved from preoperative 0 degrees to 30 degrees to postoperative 15 degrees to
      55 degrees; and the average Harris hip score improved significantly from (30.9 +/
      3.4) (2-47) to (85.1 +/- 3.1) (46-94). According to evaluation criteria, 10 hips
      got an excellent result, 3 good and 1 poor. CONCLUSION: The total hip resurfacing
      arthroplasty is an effective solution for the treatment of the younger and active
      patients with AS and it shows satisfactory short-term results. It is very
      significant to analysis the different conditions of patients so as to choose
      proper strategy.

PMID- 19594041
TI  - [Study on short-term therapeutic effects of stemless hip replacement].

PMID- 19594042
TI  - [Randomized control clinical study on third lumbar transverse process syndrome
      treated by knife needle].
AB  - OBJECTIVE: To evaluate the therapeutic effects of knife needle on third lumbar
      transverse process syndrome. METHODS: From 2007.3 to 2007.12, patients were
      divided into treatment group and control group according to the random digits
      table, 34 and 35 patients respectively. Patients in both groups were separately
      treated for 3 weeks, with knife needle in treatment group and electroacupuncture
      in control group. In treatment group, 12 patients were male and 22 patients were
      female, the average age was (42.33 +/- 7.86) years. In control group, 16 patients
      were male and 19 patients were female, the average age was (44.73 +/- 10.34)
      years. The changes of biomechanics, local tension and tenderness index were
      observed and recorded respectively before and after the therapy, and the results
      obtained from two groups were then compared with each other. The JOA score was
      used to evaluate the clinical effect. RESULTS: Sixty patients finished the
      clinical observation. The treatment efficacy was evaluated according to the JOA
      score in 60 cases. The soft tissue tension in treatment group was lower than that
      in the control group (P=0.00004). Excellent result was found in 18 cases, good in
      9 cases, fair in 3 cases and poor in 0 case. CONCLUSION: Tension relaxation by
      needle knife can effectively improve the clinical symptoms and signs of third
      lumbar transverse process syndrome.

PMID- 19594043
TI  - [Case-control study on embracing knee and rolling lumbar training for preventing
      and treating degenerative osteoarthritis of lumbar spine].
AB  - OBJECTIVE: To study therapeutic effects of embracing knee and rolling lumbar
      (EKRL) training on the pain and the function of lumbar of patients with
      degenerative osteoarthritis of lumbar spine. METHODS: From 2006.8 to 2008.1, 150
      patients with degenerative osteoarthritis of lumbar spine were randomly divided
      into the control group, EKRL training group and the combined group. In the
      control group (n=50), there were 16 females and 34 males, the average age was
      (58.8 +/- 10.2) years and the average course of diseases was (16.3 +/- 14.9)
      months. In the EKRL training group (n=50), there were 13 females and 37 males,
      the average age was (60.1 +/- 8.2) years and the average course of disease was
      (17.1 +/- 15.3) months. In the combined group (n=50), there were 15 females and
      35 males, the average ages was (59.9 +/- 11.4) years and the average course of
      diseases was (19.8 +/- 17.2) months. The patients in three groups were treated
      with Meloxicam tablets, EKRL training and two above methods combination
      respectively. After 3 weeks treatment, the curative effect, the visual analogous
      scores and the ODI indexes were observed. All the patients were followed up and
      the duration ranged from 6 to 24 months; the changes of average ODI indexes were
      observed monthly. RESULTS: After 3 weeks treatment, the therapeutic effects in
      three groups had obvious difference after Ridit analyses: there were significant
      differences between the combined group and other two groups (P<0.01), but no
      obvious differences existed in other two groups. Compared with before treatment,
      the visual analogue scale scores and the ODI indexes in three groups reduced
      significantly (P<0.01). After treatment, the visual analogue scale scores and the
      ODI indexes of the combined group had significant differences compared with those
      of other two groups (P<0.01), but the ODI indexes of other two groups had no
      obvious differences. After 6 to 24 months following-up, the monthly changes of
      average ODI indexes of EKRL training and combined groups had obvious differences
      compared with that of the control group (P<0.01). CONCLUSION: EKRL training is a
      simple, no expense and effective methods for preventing and treating degenerative
      osteoarthritis of lumbar spine.

PMID- 19594044
TI  - [Imageology analysis of perilunar dislocation and its clinical application].
AB  - OBJECTIVE: To analyze imageology manifestation of perilunar dislocation, to
      improve recognition and diagnose of the perilunar dislocation. METHODS: Fifty-six
      patients suffered from perilunar dislocation injuries were selected in our group,
      fifty-five male and one female, ranging in age from 18 to 47 years, with an
      average of 32.4 years. Roentgenograph, thin slice multi-spiral CT scanning, three
      dimensional reconstruction (3D) and multi-planar reconstruction (MPR) were
      underwent for patients before and after surgery. RESULTS: Thin slice multi-spiral
      CT thinner scanning and reconstruction provided clear images for all subjects, in
      which 56 patients had dorsal perilunate dislocations, 11 patients had
      transscaphoid perilunate dislocations, 10 patients had perilunar dislocation
      without carpus fractures, 26 patients had perilunar dislocation through centrale
      and pyramidal bone (one combined with avulsion fracture of pisiform bone), 6
      patients had trans triangular bone perilunar dislocation, 3 patients had trans
      capitate bone perilunar dislocation, 24 patients had perilunar dislocation
      combined with distal fractures of radial and ulnar, 4 patients had perilunar
      dislocation combined with dislocation of wrist joint. CONCLUSION: To be familiar
      with normal imageology anatomy of wrist joint and to master imageology
      characteristic of all types of perilunar dislocation are the basis of final
      diagnosis and prompt treatment. The thin slice multi-spiral CT scanning, three
      dimensional reconstruction (3D) and multi-planar reconstruction (MPR) provide
      clear images to diagnose the details of perilunar dislocation, and to select the
      therapeutic regimen. So it can be the first eikonic choice for perilunar
      dislocation.

PMID- 19594045
TI  - [Biomechanical study on the calcaneal fracture fixed by the self-designed
      calcaneal anatomical plate and pre-cut gudgeon].
AB  - OBJECTIVE: To study the biomechanical properties of self-designed calcaneal
      anatomical plate and pre-cut gudgeon system and its efficacy for calcaneal
      fracture fixation. METHODS: Sixteen fresh foot specimens were randomly divided
      into experimental group and the control group. Axial compressive load were
      applied to all specimens in order to create a calcaneal fracture model, and the
      maximum load and the maximum arch displacement of experimental group were
      recorded. In experimental group, self-designed intenal fixation system were
      utilized, while the AO plate internal fixation system were utilized in the
      control group. Axial compressive test were applied again to both groups, and the
      maximum load, the foot arch displacement and calcanus broadens were measured and
      recorded. RESULTS: Comparison between before and after fixing the calcaneus
      fracture by self-designed internal fixation system in experimental group, the
      difference of the maximum load was significant (P<0.01), but there was no
      significant difference (P>0.05) of the maximum arch displacement. All parameters
      were significantly different (P<0.01) between the experimental group and the
      control group. CONCLUSION: The fractured calcaneus will be able to regain normal
      foot biomechanical function after treated by self-designed internal fixation
      system, and able to support foot arch to bear great load. The self-designed
      internal fixation and pre-cut gudgeon system is considered to outperform the
      conventional AO internal fixation system with its better effectiveness and
      outcome in treating calcaneus fractures.

PMID- 19594047
TI  - [Clinical application of thoracic transverse process using as the position for
      thoracic pedicle screw implantation].
AB  - OBJECTIVE: To investigate the anatomy and clinical application of thoracic
      transverse process using as the position for thoracic pedicle screw implantation.
      METHODS: A total of 132 patients were subjected to thoracic pedicle screws
      fixation and the pedicle screws implantation position was the basis of transverse
      process. The data of anatomy, operation method for position and their
      periopereative complications were reviewed. There were 84 male and 48 female with
      their age ranging from 12 to 77 years, with an average of 32 +/- 9 years, of
      which 85 patients sufferents from thoracic vertebral fracture, 27 were thoracic
      degenerative disease, 12 were thoracic tuberculosis and 8 were thoracic tumor.
      RESULTS: A total of 788 thoracic pedicle screws were placed by free hand
      technique, and the most of screws were implanted in low thoracic segments (T10
      T12) while the least in T1. Massive hemorrhoea, leakage of cerebrospinal fluid
      and air leakage didn't occurre during operation. Thirteen thoracic pedicle screws
      were re-implanted during operation due to malposition. There are no perioperative
      complications expect for intercostal numbness founded in 2 patients and the
      symptom disappeared after 2 months therapy. CONCLUSION: It is a reliable
      technique to use the basis of transverse process as the position for pedicle
      screw implantation, which solve the difficulty of ascertainment the entry point
      of thoracic pedicle screws. Thoracic pedicle screws can be managed accurately,
      safely and reliably based on careful manipulation and imageology data.

PMID- 19594046
TI  - [Study on correlation between connective tissue growth factor, macrophage colony
      stimulating factor and cartilage degeneration in the osteoarthritis
      chondrocytes].
AB  - OBJECTIVE: To investigate the expression of connective tissue growth factor
      (CTGF) in osteoarthritis chondrocytes, and the relationship between CTGF,
      macrophage colony-stimulating factor (M-CSF) and cartilage degeneration. METHODS:
      Ten New Zealand white rabbits were randomly divided into the normal group and OA
      model group established by Hulth's method. Sections were stained with Safranin O
      for histological examination. The cartilage histological characteristics were
      observed according to the method of Mankin. Immunohistochemical staining was
      performed. Articular cartilages were observed with microscopy and the image
      analysis method was used to measure the expression intensity of CTGF and M-CSF in
      each group, and the correlations of the expression of CTGF, M-CSF and cartilage
      degeneration were analyzed by statistics. RESULTS: Immunohistochemical staining
      indicated that the expression intensity of CTGF, M-CSF in untreated group was
      significantly increased as compared with that in the normal group (P<0.05).
      Statistical analysis showed that there was a correlation between the expression
      of CTGF, M-CSF and cartilage degeneration (r=0.634, r=0.542, P<0.01
      respectively). CONCLUSION: The expression of CTGF and M-CSF protein is up
      regulated in osteoarthritis chondrocytes, which suggests that the activation of M
      CSF is involved in the production of CTGF. CTGF and M-CSF play an important role
      in the pathogenesis of cartilage degeneration.

PMID- 19594048
TI  - [Relationship between irritable bowel syndrome and unstable thoracolumbar
      vertebrae].
AB  - OBJECTIVE: To explore the cause and mechanism of irritable bowel syndrome, and to
      study the relationship between irritable bowel syndrome and unstable
      thoracolumbar vertebrae. METHODS: From 2004 to 2006, 82 patients with irritable
      bowel syndrome were treated with manipulation thoracolumbar vertebrae without any
      drug using. Among the patients, 24 patients were male and 58 patients were
      female, ranging in age from 15 to more than 61 years. RESULTS: After the
      treatment, 75 patients were cured and 7 patients improved. CONCLUSION: Unstable
      thoracolumbar vertebrae is the cause of irritable bowel syndrome. It is a simple
      and effective way by manipulation on thoracolumbar vertebrae to release
      compression and stimulation on peripheral nerve and vascular for treating this
      disease.

PMID- 19594049
TI  - [Sequential drugs treatment for central pain following spinal cord injury].
AB  - OBJECTIVE: To investigate methods and therapeutic effects of sequential drugs
      treatment for central pain following spinal cord injury. METHODS: A total of 28
      patients suffered from central pain following spinal cord injury were treated
      with sequential drugs from 1994 to 2008, including 23 males and 5 females,
      ranging in age from 25 to 59 years (mean 42 years). According to the patients'
      response to drugs, the therapy grade was adjusted step by step until the pain was
      relieved. Basing on VAS scores before and after drugs treatment, analgesic effect
      was evaluated. The first grade drugs: COX-2 inhibitors. The second grade drugs:
      Tricyclic antidepressant drugs (Amitriptyline) + COX-2 inhibitors +
      Carbamazepine. The third grade drugs: Tricyclic antidepressant drugs
      (Amitriptyline) + Gabapentin + Neurotropin/COX-2 inhibitors. RESULTS: The pain of
      all of 28 patients was relieved to different extent. The VAS scores decreased by
      23.3 +/- 1.2 in the first grade drugs treatment group. The VAS scores decreased
      by 54.5 +/- 3.8 in the second grade drugs treatment group. The VAS scores
      decreased by 65.8 +/- 5.1 in the third grade drugs treatment group (P<0.05).
      CONCLUSION: The sequential drugs treatment for central pain following spinal cord
      injury has a good analgesia effect and little adverse reaction.

PMID- 19594050
TI  - [Three-dimensional CT imaging in the treatment of children's developmental
      dislocation of hip].
AB  - OBJECTIVE: To investigate the value of 3-dimensional CT in the treatment of
      developmental dislocation of hip (DDH). METHODS: From 2003.6 to 2007.6, the
      femoral neck anteversion (FNA) and morphology of acetebulum in 53 patients with
      DDH (61 hips) were studied by three-dimensional CT imaging. Among the patients,
      12 patients were male and 41 patients were female, ranging in age from 3 to 16
      years (mean 5.6 years). Thirty-four patients had dislocation in left hip joint,
      11 patients had dislocation in right hip joints, and 8 patients had double
      dislocations. The patients were treated with Pemberton or Chiari acetabuloplasty
      and femoral osteotomy. After operation all the cases were obeserved by 3
      dimensional CT again. The femoral neck anteversions were measured and the shapes
      of new acetabulum were observed. RESULTS: Among 61 hips of DDH, the maximum
      femoral neck anteversion was 90 degrees. The minimum was 35 degrees and the
      average was (45.6 +/- 11.4) degrees. Among 45 normal hips, the average femoral
      neck anteversion was (23.5 +/- 10. 2) degrees. The acetabulum were dysplastic
      according with what were found in the operation. After operation the femoral neck
      anteversions decreased and averaged (15.6 +/- 5.8) degrees. The femoral head
      containment improved. CONCLUSION: The advantages of 3D CT scan includes
      manifestation of acetebular morphology, correct measurement of femoral neck
      anteversion and evaluation of operative procedure and efficacy. The 3-dimensional
      CT method is deserved to use widely in the treatment of developmental dislocation
      of hip in children.

PMID- 19594051
TI  - [Clinical applications of distal artery island fascial flap combined with
      intermediate split thickness skin graft].

PMID- 19594052
TI  - [Repair of skin defects of ankle and foot with modified reverse sural
      neurovascular island flap].

PMID- 19594053
TI  - [Arthroscopic treatment of meniscus injuries: a report of 36 cases].

PMID- 19594054
TI  - [Application of temporary femoral artery occlusion in the treatment of serious
      femoral soft-tissue injuries].

PMID- 19594055
TI  - [Arthroscopic diagnosis and treatment of Hoffa disease].

PMID- 19594056
TI  - [Operative treatment of floating shoulder injuries].

PMID- 19594057
TI  - [Bilateral shoulder dislocation combined with right great tuberosity fracture: a
      report of 1 case].

PMID- 19594058
TI  - [Osteoid osteoma of the scapula associated with synovitis of the shoulder: a case
      report].

PMID- 19594059
TI  - [Manipulative reduction for the treatment of calcaneal fractures in 36 cases].

PMID- 19594060
TI  - [Advances in biomechanical studies on functional training for the treatment of
      fractures].
AB  - Functional training is put a very high position in the treatment of fractures by
      Western Medicine and Traditional Chinese Medicine. The influences of functional
      training during fracture healing are very important. Functional training will
      begin after reduction and fixation and it represents the principle of the
      combination of functional training and fixation in the fracture treatment by TCM.
      Functional training makes kinds of favourable stress, which can accelerate the
      healing of fracture, but the incorrect functional training makes shear strength
      or torsion and so on, which may make interfere fracture healing. So, the
      biomechanical studies on functional training of the fracture are becoming a focus
      of fracture treatment.

PMID- 19594061
TI  - [Current study on classification of bone deficiency in the revision of total hip
      replacement].
AB  - In the revisions of total hip replacement, the classification of the bone
      deficiency includes both the acetabular and the femur. That classification of the
      acetabular bone deficiency includes the classification of Paprosky, Engh, Gross,
      Gustilo and Pasternak, Chongqing, and so on. That classification of the femoral
      bone deficiency includes AAOS, Paprosky, Mallory, and modified Mallory. All of
      the classification is not consistent for peroperative evaluation. As to the
      confusion, it is necessity to do more researches.

PMID- 19594062
TI  - [The thickness of the retrobulbar portion of the optic nerve in Graves
      ophthalmopathy measured by ultrasound].
AB  - INTRODUCTION: The clinical diagnostic of Graves ophthalmopathy is based on the
      association of ocular signs and the disease of the thyroid gland. The evolution
      of the disease involves the development of eye globe protrusion, extraocular
      muscle thickening pressuring the optic nerve, which can result in its thickness.
      OBJECTIVE: The aim of the paper is to find whether the retrobulbar optic nerve
      thickened and if there was a correlation between its possible thickening and the
      thickness of the muscles in Graves ophthalmopathy. We also wished to test the
      theory of compressive aetiology of such thickening using a 30-degree test.
      METHODS: We examined 28 patients with Graves ophthalmopathy. The thickness of the
      retrobulbar optic nerve was measured by ultrasound on a B-scan using the
      Schraeder's method and by the largest thickness of the internal muscle. RESULTS:
      The thickness of the retrobulbar portion of the optic nerve in the 52 analyzed
      eyes with signs of the disease ranged between 3.24 mm to 6.30 mm, with median of
      5.13 mm, indicating that the majority of the patients had optic nerve thickening
      rating at this value. Forty-eight eyes had a marked retrobulbar optic nerve
      thickening, with the thickening over 4 mm, while in 4 eyes with signs of Graves
      ophthalmopathy the thickness of the optic nerve was within normal limits. We
      detected that 92.3% of the patients with muscular thickening also had a directly
      proportional thickening of the retrobulbar optic nerve. By using the 30-degree
      test we confirmed the diagnosis of compressive neuropathy. CONCLUSION: Patients
      with Graves ophthalmopathy and thickened muscles, also have a thickening of the
      retrobulbar optic nerve; the rate of the thickness directly depends on the degree
      of the muscular thickness. The word is of compressive neuropathy, i.e. the
      thickness of the optic nerve is the result of subarachnoid fluid stasis caused by
      the compression on the optic nerve.

PMID- 19594063
TI  - [Multidimensional acoustic analysis of pathological voice].
AB  - INTRODUCTION: There are subjective and objective ways to examine the effects of
      vocal therapy in voice disorders. The most precise and objective check-up is the
      use of computer voice analysis. OBJECTIVE: The aim of the research was to perform
      a detailed analysis of acoustic structure of the vowel A before and after voice
      treatment in patients with vocal fold nodules in order to obtain objective
      verification of the vocal rehabilitation success. METHODS: We examined 30 female
      patients, aged 34.6 +/- 6.69 years, with vocal fold nodules. Acoustic parameters
      of voice were compared with the control group consisting of 21 subjects without
      voice pathology. In all persons the vowel A was recorded and analyzed before and
      after a month of vocal therapy. The success of the vocal therapy was tracked
      using computer analysis of vocal structure. Signal, noise and tremor parameters
      were processed. RESULTS: Of the analyzed vowel A parameters: STD, PER, JITA,
      JITT, RAP, vFO, ShdB, SHIM, APQ, VTI, SPI, FO, NHR, FTRI, eleven improved (p <
      0.05 and p < 0.01). Three parameters (FO, NHR, FTRI) changed showing improvement,
      but the obtained differences were not statistically significant (p > 0.05).
      CONCLUSION: Based on the obtained results it was concluded that vocal therapy
      gave satisfactory results, but that it should be continually applied until full
      stabilization of the voice.

PMID- 19594064
TI  - Triple pelvic osteotomy in the treatment of hip dysplasia.
AB  - INTRODUCTION: Insufficient femoral head coverage is found in a variety of
      diseases, with acetabular dysplasia as the most frequent disorder and triple
      pelvic osteotomy as the most recently introduced surgical treatment. OBJECTIVE:
      This study analyses pre- and postoperative pathoanatomic characteristics of
      triple in comparison to Salter and Chiari osteotomies, with a logistic regression
      analysis of outcome predictor and effect explanator factors in relation to the
      chosen type of operation. METHODS: The study involved 136 adolescents treated
      with Salter and Chiari osteotomies or a triple pelvic osteotomy at the Institute
      of Orthopaedic Surgery "Banjica" in Belgrade. The patients were between 10-20
      years old at the time of operation. We collected and analyzed data from all the
      patients: illness history, operative parameters, preoperative and postoperative
      pathoanatomic data. The data was statistically processed using the statistical
      software SPSS, defining standard descriptive values, and by using the appropriate
      tests of analytic statistics: t-test for dependent and independent variables,
      chi2-test, Fisher's exact test, Wilcoxon's test, parameter correlation, one-way
      ANOVA, multi-factorial ANOVA and logistic regression, according to the type of
      the analyzed data and the conditions under which the statistical methods were
      applied. RESULTS: The average CE angle after triple pelvic osteotomy was 43.5
      degrees, more improved than after the Salter osteotomy (33.0 degrees) and Chiari
      osteotomy (31.4 degrees) (F = 16.822; p < 0.01). Postoperative spherical
      congruence was also more frequent after the triple osteotomy than after the other
      two types of operations, and with a high significance. Preoperative painful
      discomfort was found to be a valid predictor of indications for the triple
      osteotomy over both Chiari and Salter osteotomies. The valid explanators of
      effect for the triple osteotomy are: postoperative joint congruence (compared to
      the Chiari osteotomy) and increase in joint coverage (compared to Salter
      osteotomy). CONCLUSION: Triple pelvic osteotomy is the method of choice in the
      management of acetabular dysplasia and other disturbances of hip joint
      containment in adolescent age.

PMID- 19594065
TI  - [Clinicopathological characteristics of Barrett's carcinoma, cardia carcinoma
      type II and distal gastric carcinoma: influence of observed parameters on the
      five-year postoperative survival of patients].
AB  - INTRODUCTION In the past two decades, the increased frequency of distal
      esophageal adenocarcinoma, esophagogastric junction and proximal gastric
      adenocarcinoma has been observed. The vast majority of these tumours are
      diagnosed in advanced stages, when the prognosis is poorer than in other gastric
      cancers. OBJECTIVE: The aim of our study was to analyze the demographic and
      clinicopathological characteristics of patients operated on for Barrett's, cardia
      and distal gastric adenocarcinomas, as well as to study the influence of
      manifestations of each cancerogenetic indication on the studied
      clinicopathological parameters and to analyze the 5-year survival rate of
      patients surgically treated for cardia adenocarcinoma in relation to the patients
      operated on for distal gastric adenocarcinoma. METHODS: We analyzed gender and
      age, tumour type, depth of tumour invasion, involvement of blood and lymph
      vessels in 66 patients surgically treated at the Centre for Oesophageal Surgery
      of the Institute for Digestive Diseases of the Belgrade Clinical Centre. RESULTS:
      Except for significant differences in the depth of tumour invasion during
      surgery, there were no other statistically significant differences between the
      studied groups of patients. In the patients operated on for Barrett's and cardia
      cancers, the tumours invaded more deeply the wall layers, i.e. they were
      significantly more invasive than the distal gastric tumour. The lymph node
      involvement was present in 87.5% of patients with Barrett's cancer, in 80% with
      cardia cancer and in 87% with distal gastric cancer. The 3-year survival rate of
      patients operated on for cardia cancer was 47.4% and the 5-year survival rate was
      31.6%, while the 3-year survival rate of patients operated on for distal gastric
      cancer was 46.2% and the 5-year survival rate was 34.6%. These differences were
      not statistically significant (Wilcoxon 0.036; p = 0.85). Singly, the patients'
      gender, cancer type and the degree of tumour differentiation had no influence on
      the length of patients' postsurgical survival rate. CONCLUSION: At the time of
      diagnosis cardia cancer and cancers developed at the location of the Barrett's
      oesophagus, developed significant deeper per continuitatem than gastric cancer.
      There were no other differences in regard to the analyzed clinicopathological
      parameters among the tumours of these three locations, and there was no
      difference between the 3-year and 5-year survival rate between the patients
      operated on for gastric cancer and cardia cancer. Each studied
      clinicopathological parameter had no influence on the illness course.

PMID- 19594066
TI  - [Effects of balneotherapy on the reactants of acute inflammation phase in
      ankylosing spondylitis].
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease that
      affects sacroiliac joints, spinal column and peripheral joints. Beside medication
      therapy, physical and balneotherapy play an important role in its complex
      treatment. OBJECTIVE: The aim of the research was to establish serum
      concentrations of C-reactive protein (CRP), alpha 1-acid glycoprotein (alpha 1
      AGP), ceruloplasmine (CP) and erythrocyte sedimentation rate (SE) before and
      after the balneotherapy in ankylosing spondylitis. METHODS: The research included
      50 AS patients according to the revised New York criteria, of mean age 43 years,
      who were treated for 14 days on the average at the Clinic for Rheumatology of the
      Institute "Niska Banja". All the patients received medications and balneotherapy
      (radioactive oligomineral baths, peloid, massage, kinesitherapy); the serum
      concentrations of CRP, al-AGP, CP and SE were measured before and after
      balneotherapy. Serum proteins were determined using original Nor Partigen plates
      Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method.
      Balneotherapy was applied individually, intensively or mildly, depending on the
      AS stage and activity phase. RESULTS: After dosed balneotherapy, a significant
      decrease in the concentrations of CP (p < 0.05), alpha1-AGP (p < 0.01) and CRP (p
      < 0.05) was registered in the serums of AS patients. ESR was not significantly
      reduced. CONCLUSION: The research proved that alpha 1-acid glycoprotein,
      ceruloplasmine and C-reactive protein represent more sensitive inflammation
      markers as compared to erythrocyte sedimentation rate. The identification of
      acute phase reactants is important in the evaluation of dosed balneotherapy
      efficiency in the treatment of ankylosing spondylitis.

PMID- 19594067
TI  - [Influence of lithotripsy modalities on complication rate].
AB  - INTRODUCTION: Localization of ureteric stones and difference in disintegration
      success are the most important factors in determining the first treatment
      approach for ureteric stones. OBJECTIVE: The aim of our study was to evaluate the
      difference in complication rate between different ureteric stone litho-tripsy
      modalities. METHODS: Two hundred sixty patients with ureteric stones were
      analyzed in a prospective bicentric study that lasted 1 year.The patients were
      divided into two groups: 1-120 patients who underwent ESWL (extracorporeal
      shockwave lithotripsy) treatment and II-140 patients who were treated
      endoscopically with ballistic lithotripsy. RESULTS Ureteroscopic lithotripsy of
      all pelvic and iliac stones was significantly more successful comparing to ESWL,
      while lumbar ureteric stone treatment with ureteroscopic lithotripsy was not
      significantly more successful than ESWL, except for lumbar stones larger than
      100mm2 that were significantly better treated endoscopically. In the I group
      complications after lithotripsy were recorded in 64 (59.3%) and in the II group
      in 58 (42.0%) patients, meaning that complications were statistically
      significantly more frequent in the I than in the II group. In the II group
      complications were significantly more often recorded after treatment of proximal
      comparing to ureteric stones of other localizations, while in the I group
      complica-tions were significantly more often detected after treatment of impacted
      stones than in the II group. CONCLUSION: Being significantly successful comparing
      to ESWL, ureteric stone treatment with ureteroscopic lithotripsy should be
      considered as the first therapeutic option for all, especially impacted stones
      located in the iliac and pelvic ureteric portion. In spite of absent statistical
      difference in the success rate, ESWL should be chosen as the first treatment
      option in all cases of lumbar ureteric stones due to lower complication rate
      except for stones larger than 100mm2that should be primarily treated
      endoscopically.

PMID- 19594069
TI  - [Internal carotid artery occlusion or subocclusion--contemporary diagnostic
      challenges: case report].
AB  - INTRODUCTION: Measurement of vessel stenosis using ultrasonography or magnetic
      resonance is still the principal method for determining the severity of carotid
      atherosclerosis and need for endarterectomy. CASE OUTLINE: A 56-year-old male was
      admitted to the Cardiovascular Institute "Dedinje" due to a clinically
      asymptomatic restenosis of the operated left internal carotid artery (ICA).
      Angiography and magnetic resonance angiography (MRA) in previous hospitalization
      had revealed occluded right ICA. However, routine duplex ultrasonography revealed
      a high-grade restenosis (85%) of the left ICA and subocclusion of the right ICA
      by an ulcerated plaque (confirmed on repeated MRA). CONCLUSION: Selective
      arteriography examination could misrepresent the degree of stenosis especially in
      patents with the ICA that seems to be occluded. MRA is considered the method of
      choice for identifying pseudo-occlusions of ICA.

PMID- 19594068
TI  - [Neurotoxicity during induction treatment of childhood acute lymphoblastic
      leukaemia--two case reports].
AB  - INTRODUCTION: During chemotherapy of acute lymphoblastic leukaemia (ALL),
      children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens
      include methotrexate, administered either intravenously or via intrathecal route.
      Although multiple drugs are used in addition to methotrexate, the acute
      neurotoxicity reported in patients is usually attributed to methotrexate. The
      acute neurotoxicity usually results in stroke-like symptoms such as aphasia,
      weakness, sensory deficits, ataxia and seizures. OUTLINE OF CASES: From 2002
      until January 2008, 32 children with ALL were diagnosed and treated at the
      Children's Hospital in Nis. The patients' age ranged from 1.5 to 16 years. They
      were treated in accordance with the protocol ALL IC-BFM 2002 (ALL
      Intercontinental Berlin Frankfurt Munster 2002). Two of the patients (6.25%)
      exhibited neurotoxicity. After the occurrence of neurological symptoms, the
      patients were ophthalmologically and neurologically examined. In addition, the
      magnetic resonance (MR) imaging, computerized tomography and
      electroencephalography were applied. The paper presents two patients, aged 9 and
      15 years respectively, who exhibited acute neurotoxicity--methotrexate
      encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and
      neurological symptoms in the course of the induction therapy. Neurotoxicity
      occurred 7 days after the third, and 3 days after the fourth intrathecal
      methotrexate therapy. MR images confirmed multi-focal morphological changes of
      brain density in one of the patients, while the other patient had normal CT
      reading. Even though the development significantly differed, the changes were
      reversible in both patients. CONCLUSION: The neurotoxicity in patients with ALL
      can be combined with significant structural changes of the brain, but also
      morphological changes can be absent. Several questions concerning aetiology and
      treatment of neurological events are raised.

PMID- 19594070
TI  - [Moderate ischemic mitral regurgitation: to operate or to ignore?].
AB  - INTRODUCTION: Moderate ischemic mitral regurgitation (MR) is characterized by
      significant, symptomatic multivessel coronary disease and mitral regurgitation 2
      3+. CASE OUTLINE: A 60-year-old patient was admitted at the Cardiovascular
      Institute "Dedinje" due to the symptoms of unstable angina pectoris. He survived
      a myocardial infarction (inferoposterolateral localization) 8 years ago. On
      admission echocardiogram revealed regional disturbances of the left ventricle
      wall with ejection fraction of 25% and mitral regurgitation 2+. The patient
      underwent a triple coronary bypass with surgical correction of mitral
      regurgitation. Postoperative course was normal. CONCLUSION: Several authors are
      against surgical correction of MR in moderate ischemic MR due to several reasons:
      revascularization of ischemic areas will improve regional wall motion and correct
      MR, while mitral valve surgery adds significantly to the operative risk of
      coronary surgery. Other authors, however, favour combined operation emphasizing
      that in many patients coronary surgery alone will not correct a moderate ischemic
      MR. Today there is no consensus whether to operate the moderate ischemic MR or to
      ignore it. Some novel studies underscore significant predictors of a long-term
      survival of these patients: NYHA (New York Heart Association) class and left
      ventricle ejection fraction. In that respect a combined operation should be
      recommended in patients with heart failure and NYHA class III and IV.

PMID- 19594071
TI  - [Sepsis as a cause of intrahepatic cholestasis].
AB  - INTRODUCTION: The causes of intrahepatic cholestasis include cholestatic viral
      hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary
      sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and
      nitric oxide cause cholestasis by impairing hepatocellular and ductal bile
      formation. CASE OUTLINE: We report a 48-year-old woman who was admitted to
      hospital due to malaise, jaundice, fever and pain in the neck. Physical
      examination revealed jaundice, tachycardia (pulse rate was 120/min), hypotension
      90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia,
      inflammatory syndrome and abnormal liver function tests indicating cholestasis
      and hepatocellular necrosis. Abdominal ultrasonography detected
      hepatosplenomegaly. Chest computed tomography showed bronchopneumonic
      infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of
      1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive,
      intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After
      the diagnosis was established the treatment with broad-spectrum antibiotics was
      carried out, resulting in the improvement of general condition of the patient,
      regression of inflammatory syndrome, disappearance of cholestasis and regression
      of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment
      did not show hepatosplenomegaly. CONCLUSION: Concerning patients with cholestasis
      of uncertain origin, we should always think of sepsis as a possible cause in
      order to start antibiotic treatment in time.

PMID- 19594072
TI  - [Gastro-duodenal ulcers with perforation caused by short-term acetylsalicylic
      acid ingestion: case report].
AB  - INTRODUCTION: Acetylsalicylic acid ingestion may cause serious gastrointestinal
      toxicity, in particular bleeding or perforated peptic ulcer. CASE OUTLINE: A 72
      year-old male patient presented with diffuse abdominal pain, malaise, and dark
      stools. Several days before hospitalization, he had cerebrovascular insult and
      began to use acetylsalicylic acid of 100 mg per day. In physical findings a
      diffusely painful sensitivity of the abdomen was detected on palpation.
      Laboratory findings revealed hyposideremic anaemia with inflammatory syndrome.
      Native abdominal x-ray did not show the presence of pneumoperitoneum. Upper
      endoscopy of the gastric corpus and antrum revealed several ulcerations 10-11 mm
      in diameter covered with fibrin, with bleeding ulceration in the angulus region
      of the lesser gastric curvature. The bulbus was oedematous and hyperaemic with a
      perforated ulcer on the anterior wall. Upper central laparotomy showed a
      perforated duodenal bulbus. The posterior wall of the bulbus was normal, while
      the anterior wall was without scarring. Given the general condition of the
      patient and local findings, interrupted suture of the ulcer was performed with
      omentoplasty. Postoperative course was uneventful. A peroral diet was initiated
      on the 4th postoperative day, and the patient was discharged on the 8th
      postoperative day. CONCLUSION: Elderly people who use acetylsalicylic acid in
      prophylaxis should take it in lower doses, with proton pump inhibitors,
      especially during the first two months.

PMID- 19594073
TI  - [Actinomycosis of the caecum simulating carcinoma in a patient with a long-term
      intrauterine device].
AB  - INTRODUCTION: Actinomycosis of the caecum is a rare, but most frequently an
      abdominally localized disease. It often simulates inflammatory malignancy, rarely
      a periappendicular abscess or Chron's disease and is only exceptionally the cause
      of intestinal obstruction or bleeding. CASE OUTLINE: The authors present a 35
      year-old woman with an intrauterine device which remained inserted for over three
      years, causing the development of pain, fever, vaginal secretion and bleeding
      that continued even after the device was removed. Ultrasonography showed a
      tumorous mass of irregular form located close to the uterus, which after a few
      months developed into a colliquation filled with pus requiring incision.
      Bacteriological examination failed to show actinomycosis. Due to the tumorous
      lesions involving the terminal ileum, appendix, caecum, ascending colon and
      omentum, a right hemicolectomy was performed. Based on histolopathological
      findings of the resected sample the diagnosis of actinomycosis was made.
      Therefore, after surgery the patient began treatment with antibiotics resulting
      in full recovery. CONCLUSION: Although rare, actinomycosis of the caecum should
      be taken into consideration in the differential diagnosis of tumorous lesions of
      the caecoascending part of the colon, particularly if the tumour is associated
      with inflammation.

PMID- 19594074
TI  - [Autosomal recessive polycystic kidney disease: case report].
AB  - INTRODUCTION: Autosomal recessive polycystic kidney disease is the most common
      heritable cystic renal disease occurring in infancy and childhood. The clinical
      spectrum of signs and symptoms of this disease is widely variable ranging from
      perinatal death to a milder progressive form, which cannot be diagnosed until
      adolescence. CASE OUTLINE: A female neonate born in the 35th/36th week of
      gestation. The findings of all standard medical examinations of the neonate done
      by the mother were within normal limits. A few days before delivery physicians at
      a regional medical centre revealed enlarged kidneys and oligohydramnios. The
      delivery was performed by caesarean section. The vital functions of the newborn
      were in critical condition so that she was referred to the University Children's
      Hospital in Belgrade. Soon after admission, despite all undertaken measures, the
      infant died. Autopsy was done at the Institute of Pathology of the Belgrade
      Clinical Centre. All findings were typical for autosomal recessive polycystic
      kidney disease. The kidneys were hugely enlarged, with cystically dilated
      collecting ducts that almost completely replaced the renal parenchyma. The lungs
      were mildly hypoplastic. The liver showed dilated portal spaces, with multiple
      irregularly branching bile ducts. The cause of death was respiratory distress and
      renal failure. CONCLUSION: In all cases of congenital anomalies of the kidney
      with lethal ending it is necessary to perform autopsy and aimed genetic
      investigation.

PMID- 19594075
TI  - [Medicolegal aspects of hospital treatment of violent mentally ill persons].
AB  - INTRODUCTION: This paper deals with medicolegal aspects of the hospital treatment
      of patients suffering from severe mental disorders and who are prone to violent
      behaviour, dangerous to self and others. Violent acts in this study were defined
      as deliberate and nonconsensual acts of actual, attempted or threatened harm to a
      person or persons, and classified into categories of any type of violence,
      physical violence and non-physical violence, which is in accordance with
      approaches used in other risk assessment researches, OUTLINE OF CASES: The
      authors present four cases of mentally ill inpatients whose violent behaviour
      toward self or other persons resulted in self-destruction and physical aggression
      against other persons. The presented cases involved: 1) self-injury in a patient
      with acute organic mental disorder after jumping through a hospital window, 2)
      suicide by drowning of a patient with acute mental disorder after escaping from
      intensive care unit, 3) suicide in a depressive patient after escaping from a low
      security psychiatry unit, 4) physical violence against body and life of other
      persons in a patient with chronic mental disorder. CONCLUSION: The presented
      cases are considered to be rare in clinical practice and risk of violent
      behaviour and the consequent danger of mentally ill inpatients may be efficiently
      predicted and prevented with appropriate hospital management based on 1) repeated
      escalation of violent behaviour and 2) protection of the patient and others.
      Hence, if the physician in order to prevent harmful consequences, does not apply
      all the necessary measures, including appropriate diagnostic and therapeutic
      procedures, as well as treatment in an adequate setting, such act is against the
      Criminal Law of the Republic of Serbia which sanctions physician's negligence.
      Also, according to the Law on Obligations of the Republic of Serbia this presents
      a legal ground for damage claim and the requirement of liability for nonmaterial
      damage within a civil procedure.

PMID- 19594076
TI  - [Gingival crevicular fluid in the diagnosis of periodontal and systemic
      diseases].
AB  - Gingival crevicular fluid (GCF) can be found in the physiologic space (gingival
      sulcus), as well as in the pathological space (gingival pocket or periodontal
      pocket) between the gums and teeth. In the first case it is a transudate, in the
      second an exudate. The constituents of GCF originate from serum, gingival
      tissues, and from both bacterial and host response cells present in the
      aforementioned spaces and the surrounding tissues. The collection and analysis of
      GCF are the noninvasive methods for the evaluation of host response in
      periodontal disease. These analyses mainly focus on inflammatory markers, such as
      prostaglandin E2, neutrophil elastase and beta-glucuronidase, and on the marker
      of cellular necrosis-aspartat aminotransferase. Further, the analysis of
      inflammatory markers in the GCF may assist in defining how certain systemic
      diseases (e.g., diabetes mellitus) can modify periodontal disease, and how
      peridontal disease can influence certain systemic disorders (atherosclerosis,
      preterm delivery, diabetes mellitus and some chronic respiratory diseases). Major
      factors which influence the results obtained from the analyses of GCF are not
      only the methods of these analyses, but the method of GCF collection as well. As
      saliva collection is less technique-sensitive than GCF collection, some
      constituents of saliva which originate from the GCF can be analysed as more
      amenable to chairside utilization.

PMID- 19594077
TI  - [New echocardiographic tehniques in optimal patient selection for cardiac
      resynchronization therapy in the treatment of chronic heart failure].
AB  - Cardiac resynchronization therapy (CRT) has important role in the contemporary
      treatment of heart failure, systolic dysfunction and mechanical disynchrony.
      Classical indications for CRT are severe heart failure (NYHA class IlI or IV), a
      broad QRS (more than 120 ms) and left ejection fraction less than 35% despite
      optimal medical therapy. Several have studies demonstrated the important role of
      echocardiography in patient selection for CRT, follow up and estimation of CRT
      effects, as well as the optimization of biventricular pacemaker. Basically, there
      are three types of cardiac asynchrony: interventricular asynchrony, between the
      right and left ventricle, intraventricular asynchrony, between the myocardial
      segments within the left ventricle and atrioventricular asynchrony, between the
      atria and ventricles. Although many echocardiographic techniques are used in
      patient selection for CRT, no ideal approach has yet been found.There are several
      techniques and parameters used in the assessment of myocardial asynchrony: two
      dimensional (2D) echocardiography, one dimensional echocardiography (M-mode),
      Doppler echocardiography, different modalities of tissue Doppler including Colour
      Coded Tissue Doppler Imaging--TDI, measurements of local tissue deformation
      indices (strain and strain rate), speckle tracking, 3D echocardiography,
      semiquantitative assessment of myocardial border, vector velocity imaging. Each
      of these techniques has advantages and limitations. A special accent in this
      revue is on the consensus report from the American Society of Echocardiography
      Dyssynchrony Writing group. According to this consensus report colour coded
      tissue Doppler is the most appropriate technique for myocardial asynchrony
      estimation and patients selection for CRT. The same group recommended that
      definitive decision for CFT implantation should not be based only on
      echocardiographic analysis, but rather on the whole clinical aspect of the
      patient.

PMID- 19594078
TI  - [Contraception: modern trends and controversies].
AB  - Ever since ancient civilizations, the possibility of preventing unwanted
      pregnancies has always been the subject of interest. All available contraception
      methods have both advantages and disadvantages, and it is up to the doctor and
      the patient to make a rational choice in each individual case. Many methods for
      temporary prevention of unwanted pregnancy are used for the purpose of
      contraception, as well as sterilization, as a permanent method. A large variety
      of contraceptives offers opting for the most suitable method for each patient,
      with the highest level of efficiency and safety. With their adequate
      administration, the rate of unwanted pregnancies should be significantly
      minimized. Methods used for contraception are constantly improving and
      simultaneously, new and more efficient ones are being developed. The research in
      the field of contraceptives is not completed yet and hopefully, in the future, we
      shall be closer to finding available, efficient, user-friendly medicaments in the
      prevention of pregnancy and sexually transmitted diseases, with minimum side
      effects, which is on the verge of perfection. Novelties in the field of
      contraception must be the theme of continuous medical education of
      gynaecologists, so that they could provide the right information and give advice
      to their patients in choosing the most adequate contraceptive.

PMID- 19594079
TI  - [Flat feet in children].
AB  - The authors describe flatfoot, as one of very frequent deformities in everyday
      medical practice. A special condition of the deformity associated with a
      calcaneal valgus position and complicated by a knee valgus position (as a
      consequence of non-treatment) is described. Also, the precise anatomy of the
      longitudinal foot arches (medial and lateral), definition and classification of
      the deformity, clinical findings and therapeutic protocols are proposed. The
      authors especially emphasise that the need for having extensive knowledge on the
      differences between a flexible and rigid flatfoot, having in mind that the
      treatment of flexible flat foot is usually not necessary, while the treatment of
      rigid flatfoot is usually unavoidable.

PMID- 19594080
TI  - [Patients' diet in "Town" and "City" hospitals in Belgrade].
AB  - The roots of hospital foundation in Serbs date from the 12th century, when the
      hospitals in the monasteries Hilandar (1199) and Studenica (1207) were
      established. The "Town" Hospital of Belgrade was founded in 1841, which had the
      status of town and regional hospital until 1881. After that, it was transformed
      into a general state-owned hospital based on the Law of National Health
      Protection. The inhabitants of Belgrade obtained a municipal hospital again in
      1935, when the "City" Hospital was founded in Zvezdara municipality, named at
      that period Bulbulder. By researching and observing hospital diet development of
      municipal hospitals in Belgrade, it was concluded that from the very beginning of
      the "Town" Hospital functioning there was awareness about its significance, place
      and role in the overall treatment of patients. Hospital diet, regardless of
      existing knowledge as the part of medical doctrines of particular time-periods,
      was often conditioned by limited hospital budgets and under the influence of
      different social movements and wartime periods

PMID- 19594081
TI  - Cohort effects.

PMID- 19594082
TI  - Self-perception of hearing ability as a strong predictor of hearing aid purchase.
AB  - BACKGROUND: Hearing threshold data are not particularly predictive of self
      perceived hearing handicap or readiness to pursue amplification. Poor
      correlations between these measures have been reported repeatedly. When a patient
      is evaluated for hearing loss, it is common to collect both threshold data and
      the individual's self-perception of hearing ability. This is done to help the
      patient make an appropriate choice related to the pursuit of amplification or
      other communication strategies. It would be valuable, though, for the audiologist
      to be able to predict which patients are ready for amplification, which patients
      require more extensive counseling before pursuing amplification, and which
      patients simply are not ready for amplification regardless of the audiometric
      data. PURPOSE: The purpose of this study was to evaluate the following question
      for its potential usefulness as a determinant of patient readiness for
      amplification: "On a scale from 1 to 10, 1 being the worst and 10 being the best,
      how would you rate your overall hearing ability?" RESEARCH DESIGN: The test
      retest reliability and the predictive value of the question, based on final
      hearing aid purchase, were evaluated in a private practice setting. STUDY SAMPLE:
      Eight hundred forty hearing-impaired adults in the age range from 18 to 95 years.
      COLLECTION AND ANALYSIS: Data were collected retrospectively from patient files.
      RESULTS AND CONCLUSION: Results were repeatable and supported the use of this
      question in similar clinical settings.

PMID- 19594083
TI  - Cochlear implant patients with superficial siderosis.
AB  - BACKGROUND: Considered a rare disorder, superficial siderosis of the central
      nervous system (SSCN) has become more frequently diagnosed in recent years. As it
      is characterized by progressive sensorineural hearing loss, patients' needs may
      surpass the capability of hearing aid technology. Despite the retrocochlear
      nature of the disorder, patients have undergone cochlear implantation (CI) with
      varying success. PURPOSE: To summarize the issues surrounding cochlear implant
      candidates with SSCN as well as highlight trends in performance postimplantation.
      RESEARCH DESIGN: Retrospective case reports of seven cochlear implant candidates
      detail the symptoms, typical audiologic presentation, and array of clinical
      issues for patients with this progressive and potentially fatal disease. RESULTS:
      Despite the retrocochlear component of a hearing loss caused by SSCN, cochlear
      implantation may be a viable option. CONCLUSIONS: It is essential that the CI
      audiologist not only be aware of the disorder but also be well versed in the
      resulting implications for the cochlear implant process. A more thorough case
      history, an expanded candidacy test battery, and knowledge of the typical
      presentation of SSCN are critical. The diagnosis of SSCN will impact expectations
      for success with the cochlear implant, and counseling should be adjusted
      accordingly.

PMID- 19594085
TI  - Evaluation of the International Outcome Inventory for Hearing Aids in a veteran
      sample.
AB  - BACKGROUND: The International Outcome Inventory for Hearing Aids (IOI-HA) was
      developed as a global hearing aid outcome measure targeting seven outcome
      domains. The published norms were based on a private-pay sample who were fitted
      with analog hearing aids. PURPOSE: The purpose of this study was to evaluate the
      psychometric properties of the IOI-HA and to establish normative data in a
      veteran sample. RESEARCH DESIGN: Survey. STUDY SAMPLE: The participants were 131
      male veterans (mean age of 74.3 years, SD = 7.4) who were issued hearing aids
      with digital signal processing (DSP). INTERVENTION: Hearing aids with DSP that
      were fitted bilaterally between 2005 and 2007. DATA COLLECTION AND ANALYSIS:
      Veterans were mailed two copies of the IOI-HA. The participants were instructed
      to complete the first copy of the questionnaire immediately and the second copy
      in two weeks. The completed questionnaires were mailed to the laboratory. The
      psychometric properties of the questionnaire were evaluated. As suggested by Cox
      and colleagues, the participants were divided into two categories based on their
      unaided subjective hearing difficulty. The two categories were (1) those with
      less hearing difficulty (none-to-moderate category) and (2) those who report more
      hearing difficulty (moderately severe+ category). The norms from the current
      veteran sample then were compared to the original, published sample. For each
      hearing difficulty category, the critical difference values were calculated for
      each item and for the total score. RESULTS: A factor analysis showed that the IOI
      HA in the veteran sample had the identical subscale structure as reported in the
      original sample. For the total scale, the internal consistency was good
      (Chronbach's alpha = 0.83), and the test-retest reliability was high (lambda =
      0.94). Group and individual norms were developed for both hearing difficulty
      categories in the veteran sample. For each IOI-HA item, the critical difference
      scores were < 1.0. This finding suggests that for any item on the IOI-HA, there
      is a 95 percent chance that an observed change of one response unit between two
      test sessions reflects a true change in outcome for a given domain. CONCLUSIONS:
      The results of this study confirmed that the psychometric properties of the IOI
      HA questionnaire are strong and are essentially the same for the veteran sample
      and the original private-pay sample. The veteran norms, however, produced higher
      outcomes than those established originally, possibly because of differences in
      the population samples and/or hearing aid technology. Clinical and research
      applications of the current findings are presented. Based on the results from the
      current study, the norms established here should replace the original norms for
      use in veterans with current hearing aid technology.

PMID- 19594084
TI  - Recognition and localization of speech by adult cochlear implant recipients
      wearing a digital hearing aid in the nonimplanted ear (bimodal hearing).
AB  - BACKGROUND: The use of bilateral amplification is now common clinical practice
      for hearing aid users but not for cochlear implant recipients. In the past, most
      cochlear implant recipients were implanted in one ear and wore only a monaural
      cochlear implant processor. There has been recent interest in benefits arising
      from bilateral stimulation that may be present for cochlear implant recipients.
      One option for bilateral stimulation is the use of a cochlear implant in one ear
      and a hearing aid in the opposite nonimplanted ear (bimodal hearing). PURPOSE:
      This study evaluated the effect of wearing a cochlear implant in one ear and a
      digital hearing aid in the opposite ear on speech recognition and localization.
      RESEARCH DESIGN: A repeated-measures correlational study was completed. STUDY
      SAMPLE: Nineteen adult Cochlear Nucleus 24 implant recipients participated in the
      study. INTERVENTION: The participants were fit with a Widex Senso Vita 38 hearing
      aid to achieve maximum audibility and comfort within their dynamic range. DATA
      COLLECTION AND ANALYSIS: Soundfield thresholds, loudness growth, speech
      recognition, localization, and subjective questionnaires were obtained six-eight
      weeks after the hearing aid fitting. Testing was completed in three conditions:
      hearing aid only, cochlear implant only, and cochlear implant and hearing aid
      (bimodal). All tests were repeated four weeks after the first test session.
      Repeated-measures analysis of variance was used to analyze the data. Significant
      effects were further examined using pairwise comparison of means or in the case
      of continuous moderators, regression analyses. The speech-recognition and
      localization tasks were unique, in that a speech stimulus presented from a
      variety of roaming azimuths (140 degree loudspeaker array) was used. RESULTS:
      Performance in the bimodal condition was significantly better for speech
      recognition and localization compared to the cochlear implant-only and hearing
      aid-only conditions. Performance was also different between these conditions when
      the location (i.e., side of the loudspeaker array that presented the word) was
      analyzed. In the bimodal condition, the speech-recognition and localization tasks
      were equal regardless of which side of the loudspeaker array presented the word,
      while performance was significantly poorer for the monaural conditions (hearing
      aid only and cochlear implant only) when the words were presented on the side
      with no stimulation. Binaural loudness summation of 1-3 dB was seen in soundfield
      thresholds and loudness growth in the bimodal condition. Measures of the
      audibility of sound with the hearing aid, including unaided thresholds,
      soundfield thresholds, and the Speech Intelligibility Index, were significant
      moderators of speech recognition and localization. Based on the questionnaire
      responses, participants showed a strong preference for bimodal stimulation.
      CONCLUSIONS: These findings suggest that a well-fit digital hearing aid worn in
      conjunction with a cochlear implant is beneficial to speech recognition and
      localization. The dynamic test procedures used in this study illustrate the
      importance of bilateral hearing for locating, identifying, and switching
      attention between multiple speakers. It is recommended that unilateral cochlear
      implant recipients, with measurable unaided hearing thresholds, be fit with a
      hearing aid.

PMID- 19594086
TI  - A comparison of presentation levels to maximize word recognition scores.
AB  - BACKGROUND: While testing suprathreshold word recognition at multiple levels is
      considered best practice, studies on practice patterns do not suggest that this
      is common practice. Audiologists often test at a presentation level intended to
      maximize recognition scores, but methods for selecting this level are not well
      established for a wide range of hearing losses. PURPOSE: To determine the
      presentation level methods that resulted in maximum suprathreshold phoneme
      recognition scores while avoiding loudness discomfort. RESEARCH DESIGN:
      Performance-intensity functions were obtained for 40 participants with
      sensorineural hearing loss using the Computer-Assisted Speech Perception
      Assessment. Participants had either gradually sloping (mild, moderate, moderately
      severe/severe) or steeply sloping losses. Performance-intensity functions were
      obtained at presentation levels ranging from 10 dB above the SRT to 5 dB below
      the UCL (uncomfortable level). In addition, categorical loudness ratings were
      obtained across a range of intensities using speech stimuli. Scores obtained at
      UCL - 5 dB (maximum level below loudness discomfort) were compared to four
      alternative presentation-level methods. The alternative presentation-level
      methods included sensation level (SL; 2 kHz reference, SRT reference), a fixed
      level (95 dB SPL) method, and the most comfortable loudness level (MCL). For the
      SL methods, scores used in the analysis were selected separately for the SRT and
      2 kHz references based on several criteria. The general goal was to choose levels
      that represented asymptotic performance while avoiding loudness discomfort. The
      selection of SLs varied across the range of hearing losses. RESULTS: Scores
      obtained using the different presentation-level methods were compared to scores
      obtained using UCL - 5 dB. For the mild hearing loss group, the mean phoneme
      scores were similar for all presentation levels. For the moderately severe/severe
      group, the highest mean score was obtained using UCL - 5 dB. For the moderate and
      steeply sloping groups, the mean scores obtained using 2 kHz SL were equivalent
      to UCL - 5 dB, whereas scores obtained using the SRT SL were significantly lower
      than those obtained using UCL - 5 dB. The mean scores corresponding to MCL and 95
      dB SPL were significantly lower than scores for UCL - 5 dB for the moderate and
      the moderately severe/severe group. CONCLUSIONS: For participants with mild to
      moderate gradually sloping losses and for those with steeply sloping losses, the
      UCL - 5 dB and the 2 kHz SL methods resulted in the highest scores without
      exceeding listeners' UCLs. For participants with moderately severe/severe losses,
      the UCL - 5 dB method resulted in the highest phoneme recognition scores.

PMID- 19594087
TI  - Effects of oral preoperative carbohydrate on early postoperative outcome after
      thyroidectomy.
AB  - BACKGROUND: Preoperative carbohydrate (CHO) reduces perioperative insulin
      resistance and improves preoperative patient comfort. We tested the hypotheses
      that preoperative CHO reduces the risk of postoperative nausea and vomiting
      (PONV) and improves early postoperative patient comfort. METHODS: Two hundred
      women scheduled for thyroidectomy were randomly allocated to drink 50 g CHO in
      400 ml of water or 0.5 g aspartam in 100 ml of water 2 h before surgery. The
      incidence and the severity of PONV, pain scores, and analgesic consumption were
      recorded postoperatively. Intensity of thirst, hunger, anxiety, fatigue were
      recorded on 100-mm visual analog scales just before the induction of anesthesia,
      2, 6, and 24 h postoperatively. RESULTS: The incidence and severity of PONV were
      similar in both groups. Patients from the CHO group reported significantly less
      thirst (P = 0.007), hunger (P = 0.04), and fatigue (P = 0.01) than patients from
      the control group. Postoperative pain scores did not differ significantly between
      both groups (P = 0.34). However patients from the CHO group requested less
      acetaminophen during the first 24 postoperative h: 3 g vs. 2 g (median, P =
      0.002). CONCLUSIONS: Oral carbohydrate before thyroidectomy improves pre- and
      postoperative patient comfort, as well as postoperative analgesia, but has no
      effect on the PONV.

PMID- 19594088
TI  - Patient-controlled intravenous analgesia as an alternative to epidural analgesia
      during labor: questioning the use of the short-acting opioid remifentanil. Survey
      in the French part of Belgium (Wallonia and Brussels).
AB  - Childbirth ranks among the most intense experiences of acute pain. Neuraxial
      analgesia (i.e. epidural or combined spinal-epidural technique) is the most
      effective way to relieve that pain but it is contraindicated or impossible to
      perform for some parturients. We designed a survey of the current use of
      analgesic alternatives to epidural analgesia (EA) for labor pain, specifically
      the use of opioid patient-controlled intravenous analgesia (PCIA), in the French
      part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the
      departmental chair of the hospitals with an obstetric unit, both in university
      and non-university centers (total of 53 centers). The questionnaire evaluated the
      availability of EA, the alternatives used when EA was contraindicated, the use of
      opioid-based PCIA for labor analgesia as well as opioid preference and doses, and
      finally the reasons for not using opioid PCIA. The response rate was 67.5% (36
      centers). Among the responding hospitals, EA was available for 68% (range 25-85%)
      of labors and deliveries. When EA was not available or contraindicated, a
      parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36)
      of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28%
      (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and
      massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic
      alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers
      and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil
      was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other
      opioids (piritramide, morphine, fentanyl) and ketamine were also administered by
      PCIA. Forty-five percents of the centers reported never using opioid PCIA by
      either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and
      unability to provide a correct supervision of the parturient during PCIA use
      (48%), opposition from the pediatricians or obstetricians (17%) or because they
      considered the technique as ineffective to relieve labor pain (17%). In
      conclusion, the survey demonstrated that, when EA is contraindicated, systemic
      opioid administered by PCIA is used in almost half of the centers (47%) and that
      remifentanil is the first choice, particularly when a live birth is expected.

PMID- 19594089
TI  - Video assisted thoracoscopic surgery (VATS) for pneumothorax: a reason for
      unscheduled surgery?
AB  - Timing of urgent surgery, with full schedules and the businesslike attitude of
      operating room management, can lead to animated discussions, affecting quality of
      care and job satisfaction. No publication appears to address the timing of
      definitive care for a stable, spontaneous, pneumothorax (SP) by unscheduled, or
      urgent, video assisted thoracoscopic surgery (VATS). We reviewed the literature
      and describe our series of 38 patients with SP and VATS. Of 185 patients with SP,
      38 were presented for VATS. Of these 29% were unscheduled. Average time between
      diagnosis of SP and VATS was 11 days, with four days between decision for VATS
      and its execution. Post-operative antibiotics were prescribed to 37% of patients.
      There was a correlation between chest drain time in situ and infective signs (p =
      0.001, rho = 0.654) as well as proven infections (p = 0.05, rho = 0.386), but not
      between for scheduled and unscheduled procedures. In conclusion, our case series
      and review did not identify reasons why VATS for SP should be performed as an
      urgent procedure, though we support more rapid planning.

PMID- 19594090
TI  - Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for cardiopulmonary
      bypass priming: the effects on postoperative bleeding and volume expansion needs
      after elective CABG.
AB  - Concerned about high dose starches and potential coagulopathy, we performed a
      double blinded randomised prospective study on the influence of gelatine or 6%
      HES 130/04 pump prime on postoperative blood loss and transfusion requirements
      after CABG surgery. METHODS: After informed consent, 157 electively scheduled
      patients were randomly allocated to 6% HES (n=85) or gelatine (n=72) CPB priming.
      Postoperatively, chest tube drainage was noted hourly during the first 24 hours
      and every unit of colloid, albumin, FFP or Packed Red Cells needed to maintain
      hemodynamic stability was carefully registered. Blood losses were standardised as
      ml blood loss/kg body weight. Three patients in the HES group were excluded from
      the study because of postoperative haemorrhage of pure surgical origin. Data
      analysis consisted in unpaired t-test and Fisher exact test where appropriate.
      RESULTS: Chest tube drainage was significantly higher at 1 hour in the HES group
      (2.38 ml/kg vs. 3.15 ml/kg, p = 0.03). At 24 hours, total blood loss was still
      higher in the HES group without reaching statistical significance (p = 0.07).
      Albumin supplements occurred more frequently in the HES group between 2 and 3
      hours postoperatively (p = 0.02). Total artificial colloid supplement was
      significantly higher in the gelatin group (13.36 versus 8.96 ml/kg, p < 0.001).
      There were no differences in the number of packed red cells, fresh frozen plasma
      or platelets transfused between the two groups. CONCLUSION: 6% HES 130/0.4 is a
      safe alternative to gelatine pump prime with a volume effect persisting longer in
      the postoperative phase, mandating less volume expansion with artificial colloid
      during the first 24 postoperative hours and not causing additional allogeneic
      blood component exposure.

PMID- 19594091
TI  - Stress takotsubo cardiomyopathy after pylorus preserving pancreaticoduodenectomy
      for cancer. A case report.
AB  - A pylorus-preserving cephalic pancreaticoduodenectomy was performed for tumor
      removal in a male elderly patient. In the following course no surgical
      complications occurred but ST-elevations and increase of Troponin T were
      observed. A coronary angiography revealed no relevant stenosis although a severe
      hypokinesis of the apex region was determined by echocardiography--a Takotsubo
      syndrome was assumed. This led to a significant prolonged clinical course. No
      residual problems remained but the cause of Takotsubo could not be identified.
      Analyzing the current knowledge, a feasible preoperative screening for this
      severe condition seems to be quite impossible.

PMID- 19594092
TI  - The peri-operative use of intra-articular local anesthetics: a review.
AB  - Acute and chronic pain are of major concern after orthopedic surgery. The
      increasing trend toward day case surgery induced the development of different
      techniques in postoperative pain control. One commonly used strategy in pain
      management after knee and shoulder joint surgery is the intra-articular (IA) use
      of local anesthetics (LA). Recent attention has been drawn to the possible
      toxicity on chondrocytes of local anesthetics. The aim of this manuscript is to
      evaluate and compare through literature review the existing evidence on the
      clinical use and possible adverse effects of intra-articular injection of local
      anesthetics peri-operatively.

PMID- 19594093
TI  - Combined spinal epidural analgesia for labor and delivery: balanced view based on
      experience and literature.

PMID- 19594094
TI  - [Guideline draft of appropriate use of 131I-MIBG for internal radiotherapy of
      neuroendocrine tumors].
AB  - I3I-MIBG has been used for therapy of unresectable neuroendocrine tumors
      including malignant pheochromocytomas and neuroblastomas in foreign countries
      since the '80s when its clinical therapeutic trials were initiated. In Japan,
      131I-MIBG for therapy has not been approved by Health and Labor Ministry,
      however, personally imported 131I-MIBG is now available in limited institutions
      for therapeutic purpose. This guideline draft was made to provide the information
      about 131I-MIBG radiotherapy including related side effects for doctors, nurses,
      patients and their families, to prevent the adverse effects of this therapy and
      to protect radiation injuries from this tracer. The appendices were also attached
      concerning practical guidance for attending physicians, patient management and
      referring physicians for their conveniences.

PMID- 19594095
TI  - [Abnormal bone marrow uptake of 99mTc-tetrofosmin in myelodysplastic syndrome
      with ineffective hematopoiesis: a case report].
AB  - Eighty-four-year-old male patient with liver cirrhosis, suffered from dyspnea on
      August 2006. Four months later, his symptom has remained and he was admitted to
      our hospital. A white blood cell decrease and anemia were observed by the blood
      test. He underwent echocardiography and 99mTc-tetrofosmin myocardial scintigraphy
      (99mTc-Tf) at rest, which showed no abnormal cardiac imaging. But 99mTc-Tf whole
      body planar imaging showed extremely increased bone marrow uptake. 99mTc-HMDP
      bone scintigraphy also showed abnormal hot spots in the same skeletal regions.
      Bone marrow biopsy revealed myelodysplastic syndrome like findings. 201Tl and
      99mTc as tracers for myocardial perfusion imagings were used to evaluate coronary
      heart disease, but increased uptake of these tracers were reported in malignant
      tumors and bone metastasis. He did not have malignant tumor or bone metastasis,
      so increased uptake of 99mTc-Tf and 99mTc-HMDP was thought to be caused by
      hyperactive flow with ineffective hematopoiesis. We report a case that abnormal
      skeletal uptake of 99mTc-Tf which was caused by ineffective hematopoiesis of
      myelodysplastic syndrome.

PMID- 19594096
TI  - [Statistical study on the self-selection bias in FDG-PET cancer screening by a
      questionnaire survey].
AB  - A questionnaire survey was performed to investigate the possible presence of self
      selection bias in 18F-FDG PET cancer screening (PET cancer screening). Responders
      to the questionnaires survey consisted of 80 healthy persons, who answered
      whether they undergo PET cancer screening, health consciousness, age, sex, and
      smoking history. The univariate and multivariate analyses on the four parameters
      were performed between the responders who were to undergo PET cancer screening
      and the responders who were not. Statistically significant difference was found
      in health consciousness between the above-mentioned two groups by both univariate
      and multivariate analysis with the odds ratio of 2.088. The study indicated that
      self-selection bias should exist in PET cancer screening.

PMID- 19594097
TI  - [The 29th report on survey of the adverse reaction to radiopharmaceuticals (the
      32nd survey in 2006)].
AB  - This survey was performed in order to investigate the incidence of adverse
      reactions to radiopharmaceuticals in FY2006 in Japan. It was based on responses
      to questionnaires sent to nuclear medicine institutions. The reply was obtained
      from 975 institutions among 1263 to which the questionnaire had been sent. Thirty
      two cases of adverse reactions were reported. A total of 1,189,127
      radiopharmaceutical administrations was reported. The incidence of adverse
      reactions per 100,000 cases was 2.7. Three cases of defect products were
      reported, and the incidence of defect products per 100,000 cases was 0.3.

PMID- 19594098
TI  - [A study on involutional melancholia].
AB  - In 1896 Kraepelin described (involutional) melancholia as a single clinical
      entity separate from manic-depressive psychosis. Because of the high incidence of
      depression in the involutional period, its symptomatic characteristics, and
      somewhat poor prognosis, this was recognized as valid at that time. Nowadays, the
      broadening concept of mood disorder denies involutional melancholia as a valid
      independent entity, and so it is included in mood disorders. A closer
      psychopathological inspection, however, still reveals several crucial
      differentiating points, which suggest that should be separated from the current
      mood disorder concept. Its cardinal symptoms are as follows: unveiled basic
      anxiety (Schneider K), specific autistic thinking (Kranz H), lack of insight,
      dissimulation, and severe suicidal thoughts. Patients fear that their innermost
      mind will be revealed, try to hide it, and even pretend to be healthy.
      Melancholic patients are believed to be at an extremely high risk of suicide.
      Difference between species and types of disease and the diagnostic hierarchial
      rule, which classifies all mental disorders into four different hierarchies
      (groups), are also referred to. The reevaluation of involutional melancholia is
      imperative for the present field of clinical psychiatry.

PMID- 19594099
TI  - [Anorexia nervosa with refeeding syndrome: prevention and treatment of RS].
AB  - Refeeding syndrome (RS), seen in the early stages of anorexia nervosa (AN)
      treatment, has not been paid sufficient attention regarding its strong
      association with poor outcomes. This report describes a case of AN restriction
      type (AN-R) with sequent RS appearance despite the introduction of progressive
      and careful low-calorie nutrition, and discusses RS treatment. The patient was a
      16-year-old female. She was first diagnosed with AN at the age of 14 when she
      went on a diet, admitted into pediatrics, and recovered: however, AN recurred
      after she started high school, and her weight decreased to 31.8 kg. She was
      admitted to pediatrics again, refused to receive treatment, discharged from the
      hospital, and introduced to our department. Soon after she came to us, her weight
      went down to 29.6 kg, and continued to decrease to 26.8 kg. She was recommended
      to receive inpatient care, but she firmly refused. A few days later, her
      experience of loss of consciousness made her agree to receive inpatient care. At
      this time, she was already weakened and had difficulty performing voluntary body
      movements as well as excretion. She was treated carefully and placed on 125
      kcal/day. On the 6th day of treatment, severe liver damage was observed, her
      serum phosphorus level went down to 2.0 mg/dL, and she was diagnosed with RS. The
      lowest concentration of serum phosphorus observed was 1.3 mg/dL with blood
      abnormality and delirium; however, our strict management with intravascular
      phosphorus administration supported her increased dietary intake, and the patient
      was able to leave the hospital on the 54th day after admission. Based on this
      experience, the pathogenesis of RS was overviewed, and RS prevention as well as
      treatment was discussed. It has been reported that low phosphorus levels are
      observed in approximately one quarter of AN patients, and, thus, immediate action
      and treatment of hypophosphatemia are necessary when considering RS occurrence.
      In this study, the observed serum phosphorus concentration was higher than the
      general reported values; however, it is critical to pay attention to any quick
      drop in the serum phosphorus level rather than the absolute value. Also, as a
      preventative method, it is important to start the treatment before the patient's
      situation becomes critical. Since eating disorders are classified as psychiatric
      disorders, treatments under involuntary hospital admission should be allowed to
      avoid the worst situation. The following are suggestions to justify protective
      hospital admissions for such cases and their minimal requirements. Such actions
      should be taken for patients who are significantly underweight or in a critical
      health condition due to sudden weight loss. It is easier for patients to adapt to
      the treatment when the condition is new-onset or short disorder duration cases
      before they become chronic problems. After the caregiver-patient medical care
      relationship has been forget and significant effort has been made to get the
      patient to agree to treatment, compulsory treatment should be implemented in
      cases in which patients do not agree to treatment to avoid life-threatening
      situations.

PMID- 19594101
TI  - [Clinical features of multiple system atrophy].
AB  - This review deals with clinical features of multiple system atrophy (MSA),
      especially on natural history, sleep disordered breathing, and nocturnal sudden
      death, based on our recent analyses of definite MSA which we experienced in our
      institute. Fiberoptic laryngoscopic examination performed under propofol
      anesthesia revealed that upper airway obstruction is caused not only by vocal
      cord abductor paralysis but also by various mechanisms including floppy
      epiglottis and stenosis at the arytenoids during inspiration. We must be cautious
      not to exacerbate upper airway obstruction by continuous positive airway pressure
      (CPAP), which is now increasingly used to treat sleep disordered breathing of
      MSA. Our analyses also demonstrated that nocturnal sudden death was the most
      frequent cause of death in our MSA cohort, and CPAP could not be a prophylactic
      measure against sudden death. In order to prevent nocturnal sudden death, a new
      project is now under way using non-invasive positive airway pressure ventilation
      (NPPV) and/or artificial ventilation associated with tracheostomy.

PMID- 19594100
TI  - [Pick's disease: clinicopathological features for antemortem diagnosis].
AB  - Frontotemporal lobar degeneration (FTLD) with ubiquitin/TDP-43-positive
      inclusions (FTLD-TDP) and Pick's disease are two major pathological substrates in
      sporadic FTLD patients. Although identifying these underlying pathologies during
      the life of the patient is crucial for specific pathology-based treatment in the
      future, adequate clinical data to infer pathologies are not available. Several
      recent studies demonstrated that Pick's disease cases tend to present clinically
      with frontotemporal dementia (FTD) or progressive non-fluent aphasia as the first
      syndrome, while sporadic FTLD-TDP cases frequently show semantic dementia. Some
      asymmetric motor disturbances (e.g., pyramidal signs, parkinsonism, and
      contracture) are frequent in sporadic FTLD-TDP during the course, but rare in
      Pick's disease. On the other hand, several previous studies have demonstrated
      that the most frequent first syndrome of FTLD-TDP with progranulin gene (PGRN)
      mutations is FTD and that neuronal loss in the frontal cortex is more severe than
      that in the temporal cortex. Therefore, it is plausible that the
      clinicopathological features of sporadic FTLD-TDP are different from those of
      Pick's disease and FTLD-TDP with PGRN mutations. Given that in vivo Abeta imaging
      will soon be put to practical use, clinical data useful for clinical
      differentiation of pathological subtypes of FTLD besides AD with atypical
      cerebral atrophy will be essential in the future.

PMID- 19594102
TI  - [Clinical features of neuroferritinopathy].
AB  - Neuroferritinopathy is an autosomal dominant basal ganglia disease with iron
      accumulation caused by a mutation of the gene encoding ferritin light polypeptide
      (FTL). Six pathogenic mutations in the FTL gene have so far been reported. One
      such mutation was found in a Japanese family, thus suggesting that a new mutation
      in the FTL gene can therefore occur anywhere in the world. The typical clinical
      features of neuroferritinopathy are dystonia (especially orofacial dystonia
      related to speech and leading to dysarthrophonia) and involuntary movement, but
      such features vary greatly among the affected individuals. The findings of excess
      iron storage and cystic changes involving the globus pallidus and the putamen on
      brain MRI. and low serum ferritin levels are characteristic in
      neuroferritinopathy. Brain histochemistry shows abnormal aggregates of ferritin
      and iron throughout the central nervous system. Iron atoms are stored in the
      central cavity of the ferritin polymer and the E-helices of ferritin play an
      important role in maintaining the central cavity. A mutation in exon 4 of the FTL
      gene is known to alter the structure of E-helices, thereby leading to the release
      of free iron and excessive oxidative stress. Iron depletion therapy by iron
      chelation in symptomatic patients has not been shown to be beneficial, however
      before the nset of clinical symptoms, such a treatment strategy may still have
      some benefit. Neuroferritinopathy should therefore be considered in all patients
      presenting with basal ganglia disorders of unknown origin. These characteristic
      MRI findings may help to differentiate neuroferritinopathy from other diseases
      showing similar clinical features.

PMID- 19594103
TI  - [Hyperalgesia with loss of temperature sensation in one side of the body due to
      pinpoint infarction of contralateral spinothalamic tract].
AB  - We report a 67-year-old man who presented sudden loss of temperature sensation
      associated with hyperalgesia in the left trunk and extremities. No abnormal
      lesions were found on routine magnetic resonance image (MRI) in the brain and
      spinal cord. He did not show common manifestations of the lateral medullary
      syndrome including vertigo, nystagmus, ataxia, Horner's syndrome and ipsilateral
      facial sensory loss. We however suspected this syndrome, because he complained of
      characteristic, severe pain and electrical sensations in one side of his body.
      Reexamined, thinly sliced T2-weighted MRI showed a very small high intensity spot
      in the right medulla, corresponding to the location of lateral spinothalamic
      tract. Oral carbamazepine was partially effective to ameliorate the intractable
      central poststroke pain.

PMID- 19594104
TI  - [Case of sporadic hemiplegic migraine with cerebellar ataxia].
AB  - A 34-year-old man was admitted with his unsteady gait, difficulty in speech and a
      paroxysmal severe headache accompanied with sensori-motor disturbance of the
      right extremities and aphasic symptom. His family history was unremarkable. His
      unsteadiness has progressed very slowly from childhood. He noted to be
      inarticulate at the age of 18 years. At the age of 33 years, he suddenly had an
      attack of severe throbbing headache, which was mainly left parietal, with nausea
      and photophobia. During the headache, his right extremities were paralyzed and he
      became aphasic. He had lost a partial memory of the event All these symptoms had
      gone within 24 hours. Thereafter, the same headache occurred about once a month.
      Neurological examination revealed a mild truncal ataxia and ataxic dysarthria.
      Electroencephalography (EEG) showed intermittent delta waves restricted over the
      left fronto-temporal region. Brain MRI showed a moderate atrophy of superior
      cerebellar vermis and anterior cerebellar lobe. The diagnosis of sporadic
      hemiplegic migraine (SHM) with cerebellar ataxia was made. Our case was very
      similar to familial hemiplegic migraine (FHM) 1, of which some families are
      accompanied with transient amnesia, cerebellar ataxia and EEG abnormality.
      Although we did not detect any mutations in CACNA1A gene previously reported in
      FHM1, our case might share same pathogenesis with FHM1.

PMID- 19594105
TI  - [Elderly hereditary hemorrhagic telangiectasia female with portosystemic
      encephalopathy].
AB  - We present a 71-year-old woman with hereditary hemorrhagic telangiectasia (HHT)
      who at age 69, had undergone total gastrectomy because of repeated upper
      gastrointestinal bleeding. A day prior to admission she began to demonstrate
      abnormal behavior. Examination showed she was restless and had higher brain
      dysfunction. Triphasic waves were seen on EEG, and a high signal in the globus
      pallidus on T1-weighted MRI. Plasma NH3 level was increased after a meal.
      Abdominal CT scan showed vascular anomalies including a portohepatic vein shunt.
      She was diagnosed with portosystemic encephalopathy. After treatment with a low
      protein diet, lactitol, and branched chain-amino acids, her clinical condition,
      plasma NH3 level after a meal, and EEG returned to normal. Because portosystemic
      shunt is rare in HHT, there have been few reports of portosystemic encephalopathy
      with this condition. However, with aging, the possibility of portosystemic
      encephalopathy increases because of age-related increases in portosystemic shunt
      volume.

PMID- 19594106
TI  - [Reliability of blood gas analyzers for measuring lactate levels in cerebrospinal
      fluid].
AB  - The lactate levels in the cerebrospinal fluid (CSF) can be used to distinguish
      bacterial meningitis from aseptic meningitis. However, it is usually difficult to
      promptly measure the lactate levels. There are certain blood gas analyzers that
      can be used to easily and promptly obtain glucose and lactose data. We
      ascertained whether the lactate and glucose levels from CSF samples can be
      analyzed by blood gas analyzers, and we subsequently compared the data obtained
      with that measured at the laboratory. In this study, we measured the cell counts
      and the protein, glucose, and lactate levels in 62 CSF samples obtained from 51
      patients. Of these 62 samples, lactate and glucose of 17 samples were also
      measured by a blood gas analyzer. There were no significant differences in the
      lactate and glucose levels between the data measured at the laboratory and that
      measured by the blood gas analyzer. In conclusion, we consider that rapid
      measurement of the lactate and glucose levels in CSF samples by blood gas
      analyzers can be considerably reliable in clinical practice.

PMID- 19594107
TI  - [Nasal flaring during hypoxemia in myotonic dystrophy and duchenne muscular
      dystrophy].
AB  - We investigated the relationship between nasal flaring and SpO2 in 19 patients
      with Duchenne muscular dystrophy (DMD) and 26 patients with myotonic dystrophy
      (DM1). In DMD patients, nasal flaring was observed when SpO2 was lower than 96%,
      while it was not seen even at 82% of SpO2 in DM1. None of the DM1 patients could
      perform voluntary nasal flaring. Nasal flaring is a useful indicator of hypoxemia
      in DMD but not in DM1. It remains to be elucidated whether the lack of nasal
      flaring in DM1 patients is due to abnormal respiratory central mechanism or nasal
      muscle weakness.

PMID- 19594108
TI  - [Ineffective thrombolytic therapy for calcified cerebral emboli originated from
      calcified internal carotid artery stenosis].
AB  - We report a 71-year-old man who presented with acute right hemiparesis and
      aphasia The admission CT and CT angiogram showed multiple small calcified emboli
      in branches of the left middle cerebral artery. The patient had shown no sign of
      improvement after intravenous thrombolytic therapy. Follow-up CT indicated acute
      multiple infarctions in the left middle cerebral artery area coincident with the
      calcified emboli. Carotid duplex sonography and cervical CT angiogram showed
      calcified plaque with ulceration at the origin of left internal carotid artery,
      which is the origin of those emboli Since calcified cerebral emboli (CCE) are
      rare, it should be further investigated if intravenous thrombolysis is effective
      in CCE.

PMID- 19594109
TI  - [MRI abnormality is not enough for diagnosis of positional vertigo associated
      with neurological diseases].

PMID- 19594110
TI  - High-throughput continuous hydrothermal synthesis of an entire nanoceramic phase
      diagram.
AB  - A novel High-Throughput Continuous Hydrothermal (HiTCH) flow synthesis reactor
      was used to make directly and rapidly a 66-sample nanoparticle library (entire
      phase diagram) of nanocrystalline Ce(x)Zr(y)Y(z)O(2-delta) in less than 12 h.
      High resolution PXRD data were obtained for the entire heat-treated library (at
      1000 degrees C/1 h) in less than a day using the new robotic beamline I11,
      located at Diamond Light Source (DLS). This allowed Rietveld-quality powder X-ray
      diffraction (PXRD) data collection of the entire 66-sample library in <1 day.
      Consequently, the authors rapidly mapped out phase behavior and sintering
      behaviors for the entire library. Out of the entire 66-sample heat-treated
      library, the PXRD data suggests that 43 possess the fluorite structure, of which
      30 (out of 36) are ternary compositions. The speed, quantity and quality of data
      obtained by our new approach, offers an exciting new development which will allow
      structure-property relationships to be accessed for nanoceramics in much shorter
      time periods.

PMID- 19594112
TI  - Synbeads porous-rigid methacrylic support: application to solid phase peptide
      synthesis and characterization of the polymeric matrix by FTIR microspectroscopy
      and high resolution magic angle spinning NMR.
AB  - Porous and rigid methacrylic Synbeads were optimized and applied efficiently to
      the solid phase peptide synthesis with the objective of improving significantly
      volumetric yields (0.33 mol/L calculated on the basis of maximum chemical
      accessibility, i.e. the maximum number of functional groups that can be acylated
      by FmocCl) as compared to swelling commercial polymers (from 0.06 to 0.12 mol/L).
      The effects of the density of functional groups and spacer length were
      investigated obtaining a chemical accessibility of the functional groups up to 1
      mmol/g(dry). High resolution magic angle spinning (HR-MAS) was exploited to
      evidence the presence of "solution-like" flexible linkers anchored on the rigid
      methacrylic backbone of Synbeads and to study the degree of functionalization by
      the Wang linker. To demonstrate the efficiency of the optimized Synbeads, the
      peptides Somatostatin and Terlipressin were synthesized. In the case of
      Somatostatin, final synthetic yields of 45 and 60% were achieved by following the
      HCTU/DIPEA and DIC/HOBt routes respectively, with the HPLC purity always higher
      than 83%. In the case of Terlipressin, the synthesis was carried out in parallel
      on Synbeads and also on TentaGel, ChemMatrix, and PS-DVB for comparison (DIC/HOBt
      route). The profiles describing the synthetic efficiency demonstrated that
      Synbeads leads to synthetic efficiency (86%) comparable to PS-DVB (96%) or
      ChemMatrix (84%). In order to gain a more precise picture of chemical and
      morphological features of Synbeads, their matrix was also characterized by
      exploiting innovative approaches based on FTIR microspectroscopy with a
      conventional source and with synchrotron radiation. A uniform distribution of the
      functional groups was evidenced through a detailed chemical mapping.

PMID- 19594113
TI  - Environmental and synthesis-dependent luminescence properties of individual
      single-walled carbon nanotubes.
AB  - Luminescence properties of individual (6,5) single-walled carbon nanotubes
      (SWNTs) were studied using continuous wave and time-resolved spectroscopy.
      Nanotubes synthesized by different methods (HiPco and CoMoCat) and dispersed in
      two different ionic surfactants were examined either in aqueous environments or
      deposited on surfaces. SWNT preparations leading to the highest luminescence
      intensities and narrowest spectral widths exhibit the longest luminescence decay
      times. This highlights the role of the nanotube environment and synthesis methods
      in the nonradiative relaxation processes of the excitonic recombination. Samples
      of HiPco nanotubes dispersed in sodium deoxycholate contained the brightest
      nanotubes in aqueous environments.

PMID- 19594111
TI  - Wasp mastoparans follow the same mechanism as the cell-penetrating peptide
      transportan 10.
AB  - We have been examining the mechanism and kinetics of the interactions of a
      selected set of peptides with phospholipid membranes in a quantitative manner.
      This set was chosen to cover a broad range of physical-chemical properties and
      cell specificities. Mastoparan (masL) and mastoparan X (masX) are two similar
      peptides from the venoms of the wasps Vespula lewisii and Vespa xanthoptera,
      respectively, and were chosen to complete the set. The rate constants for masX
      association with and dissociation from membranes are reported here for the first
      time. The kinetics of dye efflux induced by both mastoparans from phospholipid
      vesicles were also examined and quantitatively analyzed. We find that masL and
      masX follow the same graded kinetic model that we previously proposed for the
      cell-penetrating peptide transportan 10 (tp10), but with different parameters.
      This comparison is relevant because tp10 is derived from masL by addition of a
      mostly nonpolar segment of seven residues at the N-terminus. Tp10 is more active
      than the mastoparans toward phosphatidylcholine vesicles, but the mastoparans are
      more sensitive to the effect of anionic lipids. Furthermore, the Gibbs free
      energies of binding and insertion of the peptides calculated using the Wimley
      White transfer scales are in good agreement with the values derived from our
      experimental data and are useful for understanding peptide behavior.

PMID- 19594114
TI  - Pore directionality and correlation lengths of mesoporous silica channels aligned
      by physical epitaxy.
AB  - Herein we report on the alignment of mesoporous silica, a potential host for sub
      10 nm nanostructures, by controlling its deposition within patterned substrates.
      In-depth characterization of the correlation lengths (length of a linear porous
      channel), defects of the porous network (delamination), and how the silica
      mesopores register to the micrometer-sized substrate pattern was achieved by
      means of novel focused ion beam (FIB) sectioning and in situ SEM imaging, which
      to our knowledge has not previously been reported for such a system. Our findings
      establish that, under confinement, directed deposition of the sol within
      channeled substrates, where the cross-sectional aspect ratio of the channels
      approaches unity, induces alignment of the mesopores along the length of the
      channels. The pore correlation length was found to extend beyond the micrometer
      scale, with high pore uniformity from channel to channel observed with infrequent
      delamination defects. Such information on pore correlation lengths and defect
      densities is critical for subsequent nanowire growth within the mesoporous
      channels, contact layout (electrode deposition etc.), and possible device
      architectures.

PMID- 19594115
TI  - Synthesis and characterization of the dinuclear polyhydrides
      [Os(2)H(7)(PPh(i)Pr(2))(4)](+) and [Os(2)H(6)(PPh(i)Pr(2))(4)].
AB  - The dinuclear osmium polyhydride [Os(2)H(7)(PPh(i)Pr(2))(4)][HC(SO(2)CF(3))(2)]
      (1) was synthesized by the protonation of [OsH(6)(PPh(i)Pr(2))(2)] with
      bis(trifluoromethylsulfonyl)methane. Treatment with amine bases was not able to
      deprotonate 1, but reaction with potassium hydride gave the corresponding neutral
      polyhydride [Os(2)H(6)(PPh(i)Pr(2))(4)] (2). Single crystal X-ray diffraction
      revealed that 1 and 2 both crystallize in the P2(1)/c space group and are
      classical polyhydrides containing similar Os(mu-H)(3)Os cores with Os-Os
      distances of 2.5431(1) A and 2.5448(2) A, respectively. These structures
      represent rare examples of dinuclear osmium polyhydrides with six or more hydride
      ligands.

PMID- 19594117
TI  - CdCu(3)(OH)(6)(NO(3))(2): An S = (1)/(2) Kagome antiferromagnet.
AB  - The cadmium copper hydroxide nitrate, CdCu(3)(OH)(6)(NO(3))(2).0.5H(2)O, is
      furnished from oxygenated suspensions of Cu(2)O in aqueous Cd(NO(3))(2). The
      compound possesses the kagome structural motif and shows no evidence of magnetic
      ordering to temperatures as low as 5 K, despite exhibiting a Curie-Weiss
      temperature of Theta = -114 +/- 27 K, thus giving a spin frustration parameter, f
      = 22.8.

PMID- 19594116
TI  - New family of ferric spin clusters incorporating redox-active ortho-dioxolene
      ligands.
AB  - Seven new di-, tri-, tetra-, and hexanuclear iron complexes that incorporate a
      polydentate Schiff base and variously substituted catecholate ligands have been
      synthesized from the trinuclear precursor [Fe(3)(OAc)(3)(L)(3)] (1), where LH(2)
      = 2-[[(2-hydroxyethyl)imino]phenylmethyl]-phenol. These were isolated as the
      compounds [Fe(3)(OAc)(Cat)(L)(3)] (2), [Fe(6)(OAc)(2)(Cat)(4)(L)(4)] (3),
      [Fe(4)(3,5-DBCat)(2)(L)(4)] (4), [Bu(4)N][Fe(4)(OAc)(3,5-DBCat)(4)(L)(2)] (5a, 5(
      ) is the complex monoanion [Fe(4)(OAc)(3,5-DBCat)(4)(L)(2)](-)), [Fe(4)(OAc)(3,5
      DBCat)(3)(3,5-DBSQ)(L)(2)] (6), [Fe(2)(Cl(4)Cat)(2)(L)(LH(2))(H(2)O)] (7), and
      [Et(3)NH](2)[Fe(2)(Cl(4)Cat)(2)(L)(2)] (8a, 8(2-) is the complex dianion
      [Fe(2)(Cl(4)Cat)(2)(L)(2)](2-)), where CatH(2) = catechol; 3,5-DBCatH(2) = 3,5-di
      tert-butyl-catechol; 3,5-DBSQH = 3,5-di-tert-butyl-semiquinone, and Cl(4)CatH(2)
      = tetrachlorocatechol. While compounds 2-4, 5a, 7, and 8a were obtained by
      directly treating 1 with the appropriate catechol, compound 6 was synthesized by
      chemical oxidation of 5a. These compounds have been characterized by single
      crystal X-ray diffraction, infrared and UV-visible spectroscopy, voltammetry, UV
      visible spectroelectrochemistry, and magnetic susceptibility and magnetization
      measurements. An electrochemical study of the three tetranuclear complexes (4, 5(
      ), and 6) reveals multiple reversible redox processes due to the o-dioxolene
      ligands, in addition to reductive processes corresponding to the reduction of the
      iron(III) centers to iron(II). A voltammetric study of the progress of the
      chemical oxidation of compound 5a, together with a spectroelectrochemical study
      of the analogous electrochemical oxidation, indicates that there are two isomeric
      forms of the one-electron oxidized product. A relatively short-lived neutral
      species (5) that possesses the same ligand arrangement as complex 5(-) is the
      kinetic product of both chemical and electrochemical oxidation. After several
      hours, this species undergoes a significant structural rearrangement to convert
      to complex 6, which appears to be largely driven by the preference for the 3,5
      DBSQ(-) ligand to bind in a non-bridging mode. Variable temperature magnetic
      susceptibility measurements for compounds 3, 4, 5a, 6, 7, and 8a reveal behavior
      dominated by pairwise antiferromagnetic exchange interactions, giving rise to a
      poorly isolated S = 0 ground state spin for compound 3, well-isolated S = 0
      ground state spins for complexes 4, 5(-), 7 and 8(2-), and a well-isolated S =
      1/2 ground state spin for complex 6. The ground state spin values were confirmed
      by low temperature variable field magnetization measurements. The thermal
      variation of the magnetic susceptibility for compounds 3, 4, 5a, 6, 7, and 8a
      were fitted and/or simulated using the appropriate Hamiltonians to derive J
      values that are consistent with magnetostructural correlations that have been
      reported previously for alkoxo-bridged ferric complexes.

PMID- 19594118
TI  - Oxidation of the natural amino acids by a ferryl complex: kinetic and mechanistic
      studies with peptide model compounds.
AB  - Kinetic and mechanistic studies detailing the oxidation of substrates derived
      from the 20 natural amino acids by the ferryl complex [Fe(IV)(O)(N4Py)](2+) are
      described. Substrates of the general formula Ac-AA-NHtBu were treated with the
      ferryl complex under identical conditions ([Ac-AA-NHtBu] = 10 mM, [Fe] = 1 mM,
      1:1 H(2)O/CH(3)CN), and pseudo-first-order rate constants were obtained. Relative
      rate constants calculated from these data illustrated the five most reactive
      substrates; in order of decreasing reactivity were those derived from Cys, Tyr,
      Trp, Met, and Gly. Second-order rate constants were determined for these
      substrates by varying substrate concentration under pseudo-first-order
      conditions. Substrates derived from the other natural amino acids did not display
      significant reactivity, accelerating decomposition of the ferryl complex at a
      rate less than 10 times that of the control reaction with no substrate added.
      Ferryl decomposition rates changed in D(2)O/CD(3)CN for the Cys, Tyr, and Trp
      substrates, giving deuterium kinetic isotope effects of 4.3, 29, and 5.2,
      respectively, consistent with electron-transfer, proton-transfer (Cys and Trp),
      or hydrogen atom abstraction (Tyr) mechanisms. Decomposition rates for
      [Fe(IV)(O)(N4Py)](2+) in the presence of the Met and Gly substrates were
      identical in H(2)O/CH(3)CN versus D(2)O/CD(3)CN solvents. A deuterium kinetic
      isotope effect of 4.8 was observed with the labeled substrate 2,2-d(2)-Ac-Gly
      NHtBu, consistent with [Fe(IV)(O)(N4Py)](2+) abstracting an alpha-hydrogen atom
      from Ac-Gly-NHtBu and generating a glycyl radical. Abstraction of alpha-hydrogen
      atoms from amino acid substrates other than Gly and oxidation of side chains
      contained in the amino acids other than Cys, Tyr, Trp, and Met were slow by
      comparison.

PMID- 19594119
TI  - Intramolecular rotation of iron(II) dithiaethyneporphyrin double-decker complex:
      (1)H NMR studies.
AB  - The paramagnetic six-coordinated iron(II) 3,8,13,18
      tetraaryldithiaethyneporphyrin (ES(2)P)(2)Fe(II) complexes of the double-decker
      type have been synthesized using iron pentacarbonyl as the metal source. The
      complex contains two porphyrinic macrocycles coordinated to the iron(II) in the
      sandwich-like fashion as determined by (1)H NMR. The (1)H NMR spectra of
      (ES(2)P)(2)Fe(II) have been examined in detail in the 180 - 366 K temperature
      range. Functional group assignments based on the selective deuteration, analysis
      of T(1) relaxation times and the NOESY experiment have been made at 313 and 210
      K. The variable temperature (1)H NMR studies allowed to elucidate the dynamic
      behavior of (ES(2)P)(2)Fe(II) which involves rotation of dithiaethyneporphyrin
      rings around the metal ion. To account for the observed conformational
      rearrangements a cube, a square antiprism or a distorted triangular dodecahedron
      structure of (ES(2)P)(2)Fe(II) defined by the mutual orientation of two
      macrocyclic ligands have been considered. The six vertexes of a polyhedron are
      occupied by two pyrrolic nitrogens and four sulfur atoms, while two remaining
      vertexes are filled with two ethyne moieties. The dynamic rearrangements of
      (ES(2)P)(2)Fe(II) involve two enantiomeric couples of four fundamental staggered
      rotamers. The fast dynamic process engaging rotation of two dithiaethyneporphyrin
      ligands has been detected at 298 K. At low temperature range two rotamers have
      been identified as they presented the individual spectroscopic patterns.
      Considering the multiplicity of resonances the fast rotational oscillation
      involving one enantiomeric pair has been observed at 210 K, while all other
      processes are slow. The exchange between diastereomers has been confirmed at 210
      K as the EXSY correlations linking diastereomeric resonances have been detected
      at the NOESY map.

PMID- 19594120
TI  - Porous coordination polymer with pyridinium cationic surface,
      [Zn(2)(tpa)(2)(cpb)].
AB  - We have synthesized a porous coordination polymer containing a pyridinium cation
      as an organic linker and have investigated the methanol absorptive ability of the
      pyridinium cationic surface. The result implies that the pyridinium cationic
      surface participates in the strong adsorption of methanol.

PMID- 19594121
TI  - Ligand-mediated interconversion of multiply-interpenetrating frameworks in
      Cu(I)/Re(VII)-oxide hybrids.
AB  - Two new copper(I)-rhenate(VII) hybrid solids, Cu(bpy)ReO(4) (I) and
      Cu(bpy)(2)ReO(4).0.5H(2)O (II) (bpy = 4,4'-bipyridine), with 2-fold and 4-fold
      interpenetrating networks, respectively, were prepared from hydrothermal
      reactions, and their structures characterized by single-crystal X-ray diffraction
      [I, Pbca (No. 61), Z = 8, a = 10.8513(3) A, b = 12.9419(4) A, c = 15.6976(5) A;
      II, P1 (No. 2), Z = 2, a = 11.8190(4) A, b = 12.6741(4) A, c = 13.7585(5) A,
      alpha = 85.8653(13) degrees, beta = 81.6197(13) degrees, gamma = 84.0945(11)
      degrees]. The structure of I contains 6(3) nets of neutral CuReO(4) layers that
      are pillared via bpy ligands on the Cu sites {CuO(3)N(2)} to yield a 2-fold
      interpenetrating pillared-layered network. Conversely, the structure of II
      consists of a 4-fold interpenetrating diamond-type network with tetrahedral
      {CuN(4)} coordination nodes that are bridged by bpy ligands, with both H(2)O and
      ReO(4)(-) within the pores. A surprising reversible structural interconversion
      between these two interpenetrating structures is possible via the insertion and
      removal of a single bpy ligand and (1/2)H(2)O per copper atom. The structural
      interconversion is accompanied by a change in color from yellow to red for I and
      II, respectively. Measured UV-vis diffuse reflectance spectra exhibit a
      significant red-shift in the absorption edge of approximately 0.3 eV, with the
      optical bandgap size decreasing from approximately 2.5 eV to approximately 2.2 eV
      for I and II, respectively. X-ray photoelectron spectra and electronic structure
      calculations indicate that the valence band derived from the Cu 3d and N 2p
      orbitals in II are pushed higher in energy compared to those in I because of the
      coordination of the additional bpy ligand. There is a much smaller change in the
      energy of the conduction band that is derived from the Re 5d orbitals. These
      results demonstrate that the ligand-mediated structural transformations of
      (d(0)/d(10))-hybrid solids represent a new and convenient low-temperature
      approach to modulate their optical bandgap sizes toward the visible wavelengths
      for use with solar energy.

PMID- 19594122
TI  - Performance of PrBaCo2O(5+delta) as a proton-conducting solid-oxide fuel cell
      cathode.
AB  - The potential application of PrBaCo(2)O(5+delta) (PBC) double perovskite oxide as
      a cathode for a proton-conducting solid-oxide fuel cell based on a
      BaZr(0.1)Ce(0.7)Y(0.2)O(3-delta) (BZCY) electrolyte was systematically
      investigated. XRD and O(2)-TPD results demonstrated that cation exchange between
      BZCY and PBC perovskites simultaneously occurs from the formation of Co(3+)-doped
      BZCY and Y(3+)-doped PBC. This event does not significantly change the cathodic
      polarization resistance. Under real fuel cell conditions, neither the electrolyte
      nor electrode resistances were significantly affected by the phase reaction and
      morphologic change of PBC. Anode-supported cells with an electrolyte thickness of
      approximately 30 microm were successfully fabricated via a dual dry pressing
      process. Relatively high performance of 520 and 407 mW cm(-2) at 700 degrees C
      was achieved for the cell with a PBC cathode fired at 950 and 1100 degrees C,
      respectively. A low electrode polarization resistance of 0.06 ohms cm(2) was
      achieved at 700 degrees C for the PBC cathode calcined at 950 degrees C.

PMID- 19594123
TI  - Diphosphene and diphosphinylidene.
AB  - The equilibrium structures of P(2)H(2) isomers and the associated isomerization
      transition states have been investigated systematically starting from self
      consistent-field theory and proceeding to coupled cluster methods using a wide
      range of basis sets. For each structure, the geometry, energy, dipole moment,
      harmonic vibrational frequencies, and infrared intensities have been predicted.
      The global minimum has been confirmed to be planar trans-HPPH diphosphene, lying
      3.2 kcal mol(-1) below cis-HPPH with the aug-cc-pVQZ CCSD(T) method upon
      inclusion of zero-point vibrational energy corrections. Diphosphinylidene, which
      has the connectivity PPH(2) and C(2v) symmetry, lies 25.2 kcal mol(-1) above the
      global minimum. The trans-cis isomerization reaction occurs via internal rotation
      with a barrier of 35.2 kcal mol(-1) using the cc-pVQZ Mk-MRCCSD (2e/2MO) method.
      This transition state exhibits multireference character and consequently
      properties were evaluated using CASSCF, MRCI, CASPT2, and Mk-MRCCSD methods with
      various basis sets. At the aug-cc-pVQZ CCSD(T) level, the transition state for
      the isomerization reaction between trans-HPPH and diphosphinylidene (planar
      PPH(2)) is predicted to be nonplanar with a torsional angle of 101.1 degrees .
      The corresponding barrier is estimated to be 48.2 kcal mol(-1).

PMID- 19594125
TI  - Water vapor absorption in porous media polluted by calcium nitrate studied by
      time domain nuclear magnetic resonance.
AB  - Nuclear magnetic resonance relaxation analysis of liquid water (1)H nuclei in
      real porous media, selected for their similar composition (carbonate rocks) and
      different pore space architecture, polluted with calcium nitrate, is presented to
      study the kinetics of water condensation and salt deliquescence inside the pore
      space. These phenomena are responsible for deterioration of porous materials when
      exposed to environmental injury by pollution in a humid atmosphere. The theory is
      well described for simple pore geometries, but it is not yet well understood in
      real porous media with wide distributions of pore sizes and connections. The
      experiment is performed by following in time the formation of liquid water inside
      the pore space by T(1) and T(2) relaxation time distributions. The distributions
      allow one to see the effects of both the salt concentration and the pore space
      structure on the amount of water vapor condensed and its kinetics. It is shown
      that, for a given lithotype, even with different amounts of pollutant, the rate
      average relaxation time T(1ra) tends to increase monotonically with NMR signal,
      proportional to the amount of liquid water. T(1ra) is often inversely associated
      with surface-to-volume ratio. This suggests a trend toward the filling of larger
      pores as amounts of liquid water increase, but it does not indicate a strict
      sequential filling of pores in order of size and starting with the smallest; in
      fact, relaxation time distributions show clearly that this is not the case.
      Increased amounts of salt lead to both markedly increased rates and markedly
      increased amounts of water absorption. NMR measurements of amounts of water,
      together with relaxation time distributions, give the possibility of information
      on the effect of pollution in porous materials exposed to humid atmospheres but
      sheltered from liquid water, even before the absorption of large amounts of
      moisture and subsequent damage. These phenomena are of importance also in other
      fields, such as the exploitation of geothermal energy.

PMID- 19594124
TI  - Synthesis of phosphatase-stable, cell-permeable peptidomimetic prodrugs that
      target the SH2 domain of Stat3.
AB  - The synthesis of prodrugs targeted to the SH2 domain of Stat3 is reported. Using
      a convergent strategy, the pivaloyloxymethyl phosphonodiester of
      pentachlorophenyl 4-phosphonodifluoromethylcinnamate, a phosphotyrosine
      surrogate, was synthesized and used to acylate peptidomimetic fragments that were
      prepared on solid supports. Two prodrugs described here inhibited the
      phosphorylation of Stat3 in breast tumor cells.

PMID- 19594126
TI  - Confinement-induced fluid-gel transition in polymeric solutions.
AB  - The viscoelastic properties of confined polymer solutions are probed by particle
      tracking microrheology. The mean squared displacement of spherical probe
      particles embedded in the solution and the storage and loss moduli of the system
      are measured as the level of confinement is increased. It is found that those
      quantities change continuously as the confinement increases, and, at severe
      conditions, when the constrain reaches the size of the polymer molecule, the
      system undergoes a transition from a viscoelastic fluid to a gel.

PMID- 19594127
TI  - Behavior of cesium and thallium cations inside a calixarene cavity as probed by
      nuclear spin relaxation. Evidence of cation-pi interactions in water.
AB  - We have studied the complexes formed between the p-sulfonatocalix[4]arene and
      cesium or thallium metal cation, first by carbon-13 longitudinal relaxation of
      the calixarene molecule at two values of the magnetic field B(0). From the
      longitudinal relaxation times of an aromatic carbon directly bonded to a proton,
      thus subjected essentially to the dipolar interaction with that proton, we could
      obtain the correlation time describing the reorientation of the CH bond. The rest
      of this study has demonstrated that it is also the correlation time describing
      the tumbling of the whole calixarene assembly. From three non-proton-bearing
      carbons of the aromatic cycles (thus subjected to the chemical shift anisotropy
      and dipolar mechanisms), we have been able to determine the variation of the
      chemical shift anisotropy when going from the free to the complex form of the
      calixarene. These variations not only provide the location of the cation inside
      the calixarene cavity but also constitute a direct experimental proof of the
      cation-pi interactions. These results are complemented by cesium and thallium
      relaxation measurements performed again at two values of the magnetic field B(0).
      An estimation of the mean distance between the cation and the calixarene protons
      could be obtained. These measurements have also revealed an important chemical
      shift anisotropy of thallium upon complexation.

PMID- 19594128
TI  - Porous multilayer-coated PDMS stamps for protein printing.
AB  - A polyelectrolyte multilayer was assembled on top of a patterned PDMS stamp
      employing the layer-by-layer (LbL) assembly technique. By post-treatment with a
      base and further cross-linking, a porous multilayer-coated PDMS composite stamp
      was obtained. With the pore structures acting as an ink reservoir, the multiple
      printing of proteins was successfully achieved without the need to re-ink the
      stamp.

PMID- 19594131
TI  - Functional importance of GGXG sequence motifs in putative reentrant loops of 2HCT
      and ESS transport proteins.
AB  - The 2HCT and ESS families are two families of secondary transporters. Members of
      the two families are unrelated in amino acid sequence but share similar
      hydropathy profiles, which suggest a similar folding of the proteins in
      membranes. Structural models show two homologous domains containing five
      transmembrane segments (TMSs) each, with a reentrant or pore loop between the
      fourth and fifth TMSs in each domain. Here we show that GGXG sequence motifs
      present in the putative reentrant loops are important for the activity of the
      transporters. Mutation of the conserved Gly residues to Cys in the motifs of the
      Na(+)-citrate transporter CitS in the 2HCT family and the Na(+)-glutamate
      transporter GltS in the ESS family resulted in strongly reduced transport
      activity. Similarly, mutation of the variable residue "X" to Cys in the N
      terminal half of GltS essentially inactivated the transporter. The corresponding
      mutations in the N- and C-terminal halves of CitS reduced transport activity to
      60 and 25% of that of the wild type, respectively. Residual activity of any of
      the mutants could be further reduced by treatment with the membrane permeable
      thiol reagent N-ethylmaleimide (NEM). The X to Cys mutation (S405C) in the
      cytoplasmic loop in the C-terminal half of CitS rendered the protein sensitive to
      the bulky, membrane impermeable thiol reagent 4-acetamido-4'-maleimidylstilbene
      2,2'-disulfonic acid (AmdiS) added at the periplasmic side of the membrane,
      providing further evidence that this part of the loop is positioned between the
      transmembrane segments. The putative reentrant loop in the C-terminal half of the
      ESS family does not contain the GGXG motif, but a conserved stretch rich in Gly
      residues. Cysteine-scanning mutagenesis of a stretch of 18 residues in the GltS
      protein revealed two residues important for function. Mutant N356C was completely
      inactivated by treatment with NEM, and mutant P351C appeared to be the
      counterpart of mutant S405C of CitS; the mutant was inactivated by AmdiS added at
      the periplasmic side of the membrane. The data support, in general, the
      structural and mechanistic similarity between the ESS and 2HCT transporters and,
      more particularly, the two-domain structure of the transporters and the presence
      and functional importance of the reentrant loops present in each domain. It is
      proposed that the GGXG motifs are at the vertex of the reentrant loops.

PMID- 19594132
TI  - Site disorder in ice VII arising from hydrogen bond fluctuations.
AB  - Recently, multisite models used for the refinement of neutron diffraction data
      have suggested that the structure of ice VII is quite unlike that of its ordered
      counterpart, ice VIII. We investigate the oxygen site disorder by modeling the
      site displacement, obtained from periodic DFT calculations, as a function of the
      local hydrogen bond network. Then, using graph invariants to describe hydrogen
      bond fluctuations in the thermodynamic limit, we perform statistical mechanical
      calculations using the oxygen site displacement model developed here. We find
      that the probability distribution of the oxygen atom about its perfect lattice
      site more closely resembles the 100 model rather than the recently suggested 111
      model, although both models represent a simplification of the actual site
      distribution. We also find a unimodel distribution for the hydrogen bonded oxygen
      oxygen distance and a trimodel distribution for the nearest nonbonded oxygen
      oxygen distance with a peak separation of approximately 0.1 A.

PMID- 19594133
TI  - Enhanced fluorescence of proteins and label-free bioassays using aluminum
      nanostructures.
AB  - We report the enhanced intrinsic fluorescence from several proteins in proximity
      to aluminum nanostructured surfaces. Intrinsic fluorescence in proteins is
      dominated by the tryptophan residues. Intensities and lifetimes of several
      proteins with different numbers of tryptophan residues assembled on the surfaces
      of quartz or aluminum nanostructured films were measured. Immobilized protein
      molecules on the surface of an aluminum nanostructured film resulted in a
      significant fluorescence intensity enhancement (up to 14-fold) and lifetime
      decrease (up to 6-fold) compared to the quartz substrates. These large
      spectroscopic changes allow design of label-free bioassays where detection of
      binding interactions between proteins can be observed in the presence of a bulk
      sample solution. Binding of streptavidin to the biotinylated aluminum surface was
      demonstrated in the presence of 100 microg/mL bovine serum albumin in the sample
      solution by measurements of tryptophan intensity and lifetime changes.

PMID- 19594134
TI  - Nucleotide binding and allosteric modulation of the second AAA+ domain of ClpB
      probed by transient kinetic studies.
AB  - The bacterial AAA+ chaperone ClpB provides thermotolerance by disaggregating
      aggregated proteins in collaboration with the DnaK chaperone system. Like many
      other AAA+ proteins, ClpB is believed to act as a biological motor converting the
      chemical energy of ATP into molecular motion. ClpB has two ATPase domains, NBD1
      and NBD2, on one polypeptide chain. The functional unit of ClpB is a
      homohexameric ring, with a total of 12 potential nucleotide binding sites.
      Previously, two separate constructs, one each containing NBD1 or NBD2, have been
      shown to form a functional complex with chaperone activity when mixed. Here we
      aimed to elucidate the nucleotide binding properties of the ClpB complex using
      pre-steady state kinetics and fluorescent nucleotides. For this purpose, we first
      disassembled the complex and characterized in detail the binding kinetics of a
      construct comprising NBD2 and the C-terminal domain of ClpB. The monomeric
      construct bound nucleotides very tightly. ADP bound 2 orders of magnitude more
      tightly than ATP; this difference in binding affinity resulted almost exclusively
      from different dissociation rate constants. The nucleotide binding properties of
      NBD2 changed when this construct was complemented with a construct comprising
      NBD1 and the middle domain. Our approach shows how complex formation can
      influence the binding properties of the individual domains and allows us to
      assign nucleotide binding features of this highly complex, multimeric enzyme to
      specific domains.

PMID- 19594136
TI  - Direct quantitation of the quorum sensing signal, autoinducer-2, in clinically
      relevant samples by liquid chromatography-tandem mass spectrometry.
AB  - Quorum Sensing is a type of bacterial cell-to-cell signaling that allows for cell
      density dependent regulation of gene expression. Many of the behaviors mediated
      by quorum sensing are critical for bacterial colonization or infection, and
      autoinducer-2 has been proposed as a universal interspecies signaling molecule
      that allows multispecies colonies of bacteria, e.g., biofilms or dental plaque,
      to behave as pseudomulticellular organisms. However, the direct detection of
      autoinducer-2 has been difficult, leaving the in vivo relevance of this signal in
      question. Herein we report a liquid chromatography-tandem mass spectrometric
      technique that enables reproducible, quantitative, and sensitive measurement of
      the concentration of autoinducer-2 from a variety of sources. This technique was
      applied to the detection of autoinducer-2 from Escherichia coli and Vibrio
      harveyi in proof-of-concept studies and was then used to directly measure the
      concentration of the signal produced by oral bacteria in human saliva.

PMID- 19594135
TI  - Solution structural dynamics of HIV-1 reverse transcriptase heterodimer.
AB  - Crystal structures and simulations suggest that conformational changes are
      critical for the function of HIV-1 reverse transcriptase. The enzyme is an
      asymmetric heterodimer of two subunits, p66 and p51. The two subunits have the
      same N-terminal sequence, with the p51 subunit lacking the C-terminal RNase H
      domain. We used hydrogen exchange mass spectrometry to probe the structural
      dynamics of RT. H/D exchange revealed that the fingers and palm subdomains of
      both subunits form the stable core of the heterodimer. In the crystal structure,
      the tertiary fold of the p51 subunit is more compact than that of the polymerase
      domain of the p66 subunit, yet both subunits show similar flexibility. The p66
      subunit contains the polymerase and RNase H catalytic sites. H/D exchange
      indicated that the RNase H domain of p66 is very flexible. The beta-sheet beta12
      beta13-beta14 lies at the base of the thumb subdomain of p66 and contains highly
      conserved residues involved in template/primer binding and NNRTI binding. Using
      the unique ability of hydrogen exchange mass spectrometry to resolve slowly
      interconverting species, we found that beta-sheet beta12-beta13-beta14 undergoes
      slow cooperative unfolding with a t(1/2) of <20 s. The H/D exchange results are
      discussed in relation to existing structural, simulation, and sequence
      information.

PMID- 19594137
TI  - Heteroligand molecular "stirrups" using conformationally flexible ditopic pyridyl
      pyrazolyl ligands.
AB  - Heteroligand molecular "stirrups" form by the self-assembly of flexible ditopic
      ligands in combination with 4,4'-bipyridine and [(dppp)Pd)](2+). Crystallographic
      analysis shows that the ligands, bis[3-(4-pyridyl)pyrazolyl]-m-xylene
      (mXy(4py3pz)) and bis[4-(4-pyridyl)pyrazolyl]-p-xylene (pXy(4py4pz)) form
      complexes of the type [{(dppp)Pd}(2)(4,4'-bipy)(L)].4OTf (1.4OTf and 2.4OTf,
      respectively) in the solid state, with remarkably similar structures considering
      the differences in substitution patterns between the two ligands. The self
      assembly of both 1(4+) and 2(4+) is assisted by face-to-face pi interactions on
      the exterior of the macrocycle between the phenyl rings of the dppp ligands and
      the pyridyl groups of the ditopic ligands.

PMID- 19594139
TI  - Oxidative C-C bond formation (Scholl reaction) with DDQ as an efficient and
      easily recyclable oxidant.
AB  - DDQ in the presence of an acid is known to oxidize a variety of aromatic donors
      to the corresponding cation radicals. Herein, we now demonstrate that the
      DDQ/H(+) system can be effectively utilized for the oxidative C-C bond formations
      or biaryl synthesis. The efficient preparation of a variety of polyaromatic
      hydrocarbons including graphitic hexa-peri-hexabenzocoronenes, ease of isolation
      of the clean products, and ready regeneration of DDQ from easily recovered
      reduced DDQ-H(2) advances the use of DDQ/H(+) for Scholl reactions.

PMID- 19594140
TI  - Computational simulations of the interactions between acetyl-coenzyme-A
      carboxylase and clodinafop: resistance mechanism due to active and nonactive site
      mutations.
AB  - Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase; EC
      6.4.1.2) herbicides represent a major problem for the sustainable development of
      modern agriculture. In the present study, extensive computational simulations,
      including homology modeling, molecular dynamics (MD) simulations, and molecular
      mechanics-Poisson-Boltzmann surface area (MM/PBSA) calculations, have been
      carried out to uncover the detailed molecular mechanism of Alopecurus myosuroides
      resistance to clodinafop, a commercial herbicide targeting ACCase. All the
      computational model and energetic results indicated that W374C, I388N, D425G, and
      G443A mutations have great effects on the conformational change of the binding
      pocket and the hydrogen-bonding interactions. The pi-pi interaction between
      ligand and the residue of Phe377 and Tyr161', playing an important contribution
      to the binding affinity, were decreased after mutations. In addition, the
      hydrogen-bonding interactions between clodinafop and the residues (Ile158' and
      Ala54') disappeared or decreased significantly upon mutation. As a result, the
      mutant-type ACCase has a lower affinity for the inhibitor binding than the wild
      type enzyme, which accounts for the molecular basis of herbicidal resistance. The
      structural and mechanistic insights obtained from the present study will provide
      a valuable clue for future designing of a promising inhibitor to reduce drug
      resistance associated with both active and nonactive site mutations.

PMID- 19594141
TI  - Cardenolide glycosides of Thevetia peruviana and triterpenoid saponins of
      Sapindus emarginatus as TRAIL resistance-overcoming compounds.
AB  - A screening study for TRAIL resistance-overcoming activity was carried out, and
      activity-guided fractionations of Thevetia peruviana and Sapindus emarginatus led
      to the isolation of four cardenolide glycosides (1-4) and four triterpenoid
      saponins (5-8), respectively. In particular, cardenolide glycosides (1 and 2)
      from T. peruviana were shown to have a significant reversal effect on TRAIL
      resistance in human gastric adenocarcinoma cells, and real-time PCR showed that
      thevefolin (2) enhanced mRNA expression of death receptor 4 (DR4) and DR5. In
      addition, 1H and 13C NMR characterizations are shown for thevefolin (2) for the
      first time.

PMID- 19594143
TI  - Influence of chiral ionic liquids on stereoselective fluorescence quenching by
      photoinduced electron transfer in a naproxen dyad.
AB  - In a previous study of a naproxen dyad in a pair of N-methylimidazoliummethyl
      menthylether-NTf(2) chiral ionic liquids (J. Phys. Chem. B 2008, 112, 7555), we
      observed that though intramolecular electron transfer was impeded, a consistent
      small stereodifferentiation in the fluorescence lifetime of the dyad was
      obtained. We proposed that this discrimination was purely electronic in nature
      and did not arise from geometrical effects, which can influence nonradiative rate
      processes, such as intramolecular electron transfer. In our present work, we have
      studied the interaction of the same chiral naproxen dyad molecule in both the
      previously studied menthyl-based NTf(2) ionic liquids and also in
      bis(tertrabutylphosphonium) (TBP) d-,l-tartrate ionic liquids. Unlike in the
      menthyl-based IL pair, the amount of quenching is different in the bis(TBP)
      tartrate enantiomeric liquids and the tartrate enantiomers have a different
      temperature dependence on the nonradiative rate of the dyad. This chiral
      discrimination most likely arises from the steric effects of the different
      conformations of the chiral molecules. We have shown that the viscosity and
      polarity of the solvents can influence the rate of electron transfer. On the
      other hand, no such electron transfer quenching is observed in the menthyl-based
      NTf(2) IL solvents. To our knowledge, this is the first example of chiral ionic
      liquids inducing a stereoselective fluorescence quenching by photoinduced,
      intramolecular electron transfer.

PMID- 19594142
TI  - Chiral crystallization: freezing a rapid Cope rearrangement in the solid state.
AB  - Homotropylidene and its derivatives undergo a fast Cope rearrangement. A
      homotropylidene system (cyclooctatetraene dimer) is reported that racemizes
      rapidly by such a valence isomerization in solution at room temperature. In the
      solid state, however, this rearrangement is frozen, and the single crystals
      precipitating from the racemic solution contain only one enantiomer. Since very
      large crystals can be grown, the racemic solution in principle can be converted
      into a single enantiomer by crystallization.

PMID- 19594144
TI  - Carbon-carbon formation via Ni-catalyzed Suzuki-Miyaura coupling through C-CN
      bond cleavage of aryl nitrile.
AB  - The Suzuki-Miyaura coupling of aryl nitriles with aryl/alkenyl boronic esters is
      reported. With this method, the cyano group could be applied as a protecting
      group of arenes and finally as a leaving group to further construct polyaryl
      scaffolds.

PMID- 19594145
TI  - The energy landscape for the interaction of the family 1 carbohydrate-binding
      module and the cellulose surface is altered by hydrolyzed glycosidic bonds.
AB  - A multiscale simulation model is used to construct potential and free energy
      surfaces for the carbohydrate-binding module [CBM] from an industrially important
      cellulase, Trichoderma reesei cellobiohydrolase I, on the hydrophobic face of a
      coarse-grained cellulose Ibeta polymorph. We predict from computation that the
      CBM alone exhibits regions of stability on the hydrophobic face of cellulose
      every 5 and 10 A, corresponding to a glucose unit and a cellobiose unit,
      respectively. In addition, we predict a new role for the CBM: specifically, that
      in the presence of hydrolyzed cellulose chain ends, the CBM exerts a
      thermodynamic driving force to translate away from the free cellulose chain ends.
      This suggests that the CBM is not only required for binding to cellulose, as has
      been known for two decades, but also that it has evolved to both assist the
      enzyme in recognizing a cellulose chain end and exert a driving force on the
      enzyme during processive hydrolysis of cellulose.

PMID- 19594146
TI  - Generation and geometrical analysis of dense clusters with variable fractal
      dimension.
AB  - The generation and geometrical analysis of clusters composed of rigid
      monodisperse primary particles with variable fractal dimension, df, in the range
      from 2.2 to 3 are presented. For all generated aggregate populations, it was
      found that the dimensionless aggregate mass, i, and the aggregate size,
      characterized by the radius of gyration, Rg, normalized by the primary particle
      radius, Rp, follow a fractal scaling, i = kf(Rg/Rp)df. Furthermore, the obtained
      prefactor of the fractal scaling, kf, is related to df according to kf = 4.46df
      2.08, which is in agreement with literature data. For cases when df cannot be
      directly determined from light scattering or confocal laser scanning microscopy,
      it can be estimated from its relation with a perimeter fractal dimension, dpf, or
      a chord fractal dimension, dcf, both obtained from 2D projection of aggregates. A
      relation between df and dpf of the form df = or-1.5dpf + 4.4 was developed by
      fitting data obtained in this work for 2.2 < df < 3 together with data of Lee and
      Kramer [Adv. Colloid Interface Sci. 2004, 112(1-3), 49-57] for 1.8 < df < 2.4. It
      was found that the method of determining df via dpf is very robust with respect
      to an artificially introduced blur. In contrary, a relation between df and dcf
      could only be established for the case of ideal optical analysis, while the
      introduction of blur results in a significant effect on the chord length
      distribution (and its moments), up to the point of impeding the evaluation of
      dcf. Hence, for compact aggregates, it is recommended to determine df from dpf by
      applying the proposed relation, which is valid in a broad range of df relevant
      for industrial praxis, with little effect of blur on it. Apart from scaling
      relations with respect to aggregate mass and size, it was found that the 3D
      quantities, i and Rg, can be directly related to the area squared over perimeter,
      A2/P, and the 2D radius of gyration, Rg,2D, respectively, which are obtained from
      2D projections. In particular, the following two relations are provided: i =
      4.5(A2/P)0.9 and Rg/Rp = 1.47 (Rg,2D/Rp)0.99.

PMID- 19594148
TI  - The influence of bilayer composition on the gel to liquid crystalline transition.
AB  - We report molecular dynamics simulations of bilayers using a united atom model
      with explicit solvent molecules. The bilayer consists of the single tail cationic
      surfactant behenyl trimethyl ammonium chloride (BTMAC) with stearyl alcohol (SA)
      as the cosurfactant. We study the gel to liquid crystalline transitions in the
      bilayer by varying the amount of water at fixed BTMAC to SA ratio as well as by
      varying the BTMAC to SA ratio at fixed water content. The bilayer is found to
      exist in the tilted, L(beta') phase at low temperatures, and for the compositions
      investigated in this study, the L(beta') to L(alpha) melting transition occurred
      in the temperature range 330-338 K. For the highest BTMAC to SA composition (2:3
      molar ratio), a diffuse headgroup-water interface is observed at lower
      temperatures, and an increase in the d-spacing occurs prior to the melting
      transition. This pretransition swelling is accompanied by a sharpening in the
      water density variation across the headgroup region of the bilayer. Signatures of
      this swelling effect which can be observed in the alkane density distributions,
      area per headgroup, and membrane thickness are attributed to the hydrophobic
      effect. At a fixed bilayer composition, the transition temperature (>338 K) from
      the L(beta') to L(alpha) transition obtained for the high water content bilayer
      (80 wt %) is similar to that obtained with low water content (54.3 wt %),
      confirming that the melting transition at these water contents is dominated by
      chain melting.

PMID- 19594147
TI  - General library-based Monte Carlo technique enables equilibrium sampling of semi
      atomistic protein models.
AB  - We introduce "library-based Monte Carlo" (LBMC) simulation, which performs
      Boltzmann sampling of molecular systems based on precalculated statistical
      libraries of molecular-fragment configurations, energies, and interactions. The
      library for each fragment can be Boltzmann distributed and thus account for all
      correlations internal to the fragment. LBMC can be applied to both atomistic and
      coarse-grained models, as we demonstrate in this "proof-of-principle" report. We
      first verify the approach in a toy model and in implicitly solvated all-atom
      polyalanine systems. We next study five proteins, up to 309 residues in size. On
      the basis of atomistic equilibrium libraries of peptide-plane configurations, the
      proteins are modeled with fully atomistic backbones and simplified Go-like
      interactions among residues. We show that full equilibrium sampling can be
      obtained in days to weeks on a single processor, suggesting that more accurate
      models are well within reach. For the future, LBMC provides a convenient platform
      for constructing adjustable or mixed-resolution models: the configurations of all
      atoms can be stored at no run-time cost, while an arbitrary subset of
      interactions is "turned on".

PMID- 19594150
TI  - Dynamics of imidazolium ionic liquids from a combined dielectric relaxation and
      optical Kerr effect study: evidence for mesoscopic aggregation.
AB  - We have measured the intermolecular dynamics of the 1,3-dialkylimidazolium-based
      room-temperature ionic liquids (RTILs) [emim][BF(4)], [emim][DCA], and
      [bmim][DCA] at 25 degrees C from below 1 GHz to 10 THz by ultrafast optical Kerr
      effect (OKE) spectroscopy and dielectric relaxation spectroscopy (DRS) augmented
      by time-domain terahertz and far-infrared FTIR spectroscopy. This concerted
      approach allows a more detailed analysis to be made of the relatively featureless
      terahertz region, where the higher frequency diffusional modes are strongly
      overlapped with librations and intermolecular vibrations. Of greatest interest
      though, is an intense low frequency (sub-alpha) relaxation that we show is in
      accordance with recent simulations that have reported mesoscopic structure
      arising from aggregates or clusters--structure that explains the anomalous and
      inconveniently high viscosities of these liquids.

PMID- 19594149
TI  - Ethanol oxidation: kinetics of the alpha-hydroxyethyl radical + O2 reaction.
AB  - Bioethanol is currently a significant gasoline additive and the major blend
      component of flex-fuel formulations. Ethanol is a high-octane fuel component, and
      vehicles designed to take advantage of higher octane fuel blends could operate at
      higher compression ratios than traditional gasoline engines, leading to improved
      performance and tank-to-wheel efficiency. There are significant uncertainties,
      however, regarding the mechanism for ethanol autoignition, especially at lower
      temperatures such as in the negative temperature coefficient (NTC) regime. We
      have studied an important chemical process in the autoignition and oxidation of
      ethanol, reaction of the alpha-hydroxyethyl radical with O2(3P), using first
      principles computational chemistry, variational transition state theory, and Rice
      Ramsperger-Kassel-Marcus (RRKM)/master equation simulations. The alpha
      hydroxyethyl + O2 association reaction is found to produce an activated alpha
      hydroxy-ethylperoxy adduct with ca. 37 kcal mol(-1) of excess vibrational energy.
      This activated adduct predominantly proceeds to acetaldehyde + HO(2), with
      smaller quantities of the enol vinyl alcohol (ethenol), particularly at higher
      temperatures. The reaction to acetaldehyde + HO2 proceeds with such a low barrier
      that collision stabilization of C2O3H5 isomers is unimportant, even for high
      pressure/low-temperature conditions. The short lifetimes of these radicals
      precludes the chain-branching addition of a second O2 molecule, responsible for
      NTC behavior in alkane autoignition. This result helps to explain why ignition
      delays for ethanol are longer than those for ethane, despite ethanol having a
      weaker C-C bond energy. Given its relative instability, it is also unlikely that
      the alpha-hydroxy-ethylperoxy radical acts as a major acetaldehyde sink in the
      atmosphere, as has been suggested.

PMID- 19594151
TI  - Spectral signatures of intramolecular charge transfer process in beta-enaminones:
      a combined experimental and theoretical analysis.
AB  - In this paper, we present spectroscopic signatures of intramolecular charge
      transfer (ICT) and effects of solvent on the ICT process in 3-(phenylamino)-2
      cyclohexen-1-one (PACO), a member of the well-known molecular family, the beta
      enaminones. The dual fluorescence in the steady state emission spectra of the
      molecule in polar solvents indicates the occurrence of ICT, which is further
      supported by time-resolved studies, using time correlated single photon counting
      technique with picosecond resolution. To understand the nature of the charge
      transfer, pH dependent studies of the probe in water were performed, where a
      quenching of fluorescence was observed even in the presence of very low
      concentrations of acids. Solvent induced fluorescence quenching was observed in
      ethanol and methanol. The ICT process was also investigated by quantum chemical
      calculations. To understand the role of solvents in the ICT process, we have
      theoretically studied the macroscopic and microscopic solvation of the probe in
      water. The absorption spectra of the molecule in the gas phase as well as in
      water were simulated using time dependent density functional theory with cc-pVTZ
      basis set and self-consistent reaction field theory that models macroscopic
      solvation. The possibility of microscopic solvation in water was probed
      theoretically and the formation of 1:3 molecular clusters by PACO with water
      molecules has been confirmed. Our findings could have a bearing on pH sensing
      applications of the probe.

PMID- 19594153
TI  - Supramolecular patterns controlled by electron interference and direct
      intermolecular interactions.
AB  - Whereas all 230 three-dimensional space groups occur in organic crystals, out of
      only 17 plane groups some highly symmetric ones such as p31m have not yet been
      observed in two-dimensional (2D) crystals of organic molecules. Here a kagome
      network with p31m symmetry is reported for cobalt phthalocyanine on Cu(111). This
      unusual structure results from substrate-induced reduction of molecular symmetry
      and substrate-mediated interaction via quantum interference of surface electrons.
      These interactions provide additional control over the symmetry of 2D crystals of
      phthalocyanines and lead to a variety of other symmetries in self-assembled
      arrays.

PMID- 19594152
TI  - Charge density and electrostatic interactions of fidarestat, an inhibitor of
      human aldose reductase.
AB  - The charge density and the topological features of fidarestat, an inhibitor of
      human aldose reductase, have been determined from ultra high-resolution X-ray
      diffraction data at 100 K. The modeled electron density was used to calculate the
      electrostatic interaction energy of fidarestat and its (2R,4S) stereoisomer with
      the human aldose reductase by using the ELMAM database as coded in the MoPro
      program. Such calculation may be extended to other protein complexes for which
      accurate high resolution X-ray data are available. The paper also discusses the
      hydrogen bonds in the fidarestat crystal. There are notably two hydrogen bonds
      with a pi system as an acceptor. All the chemical bonds and the intermolecular
      interactions, especially these two pi...H bonds, have been quantitatively studied
      by topological analysis. The three-dimensional electrostatic potential calculated
      on the molecular surface emphasizes the preferential polar binding sites of
      fidarestat. Theses interacting features in the molecule are crucial for drug
      receptor recognition. The interactions between chemical groups in the crystal are
      also analyzed by computing the electrostatic energy using the latest advancements
      of the MoPro crystallographic software. The complexes of fidarestat and its
      (2R,4S) stereoisomer with human aldose reductase were modeled with a multipolar
      atom model transferred from our experimental electron density database. Accurate
      estimation of electrostatic interaction energy between inhibitors and the main
      residues of the protein active site is derived from this high detail level of the
      electron density.

PMID- 19594154
TI  - Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray
      diagnostics.
AB  - The generation of high quality plasma from whole blood is of major interest for
      many biomedical analyses and clinical diagnostic methods. However, it has proven
      to be a major challenge to make use of microfluidic separation devices to process
      fluids with high cell content, such as whole blood. Here, we report on an
      acoustophoresis based separation chip that prepares diagnostic plasma from whole
      blood linked to a clinical application. This acoustic separator has the capacity
      to sequentially remove enriched blood cells in multiple steps to yield high
      quality plasma of low cellular content. The generated plasma fulfills the
      standard requirements (<6.0 x 10(9) erythrocytes/L) recommended by the Council of
      Europe. Further, we successfully linked the plasmapheresis microchip to our
      previously developed porous silicon sandwich antibody microarray chip for
      prostate specific antigen (PSA) detection. PSA was detected by good linearity
      (R(2) > 0.99) in the generated plasma via fluorescence readout without any signal
      amplification at clinically relevant levels (0.19-21.8 ng/mL).

PMID- 19594155
TI  - Interfacial electron transfer in TiO(2) surfaces sensitized with Ru(II)
      polypyridine complexes.
AB  - Studies of interfacial electron transfer (IET) in TiO(2) surfaces functionalized
      with (1) pyridine-4-phosphonic acid, (2) [Ru(tpy)(tpy(PO(3)H(2)))](2+), and (3)
      [Ru(tpy)(bpy)(H(2)O)-Ru(tpy)(tpy(PO(3)H(2)))](4+) (tpy = 2,2':6,2''-terpyridine;
      bpy = 2,2'-bipyridine) are reported. We characterize the electronic excitations,
      electron injection time scales, and interfacial electron transfer (IET)
      mechanisms through phosphonate anchoring groups. These are promising alternatives
      to the classic carboxylates of conventional dye-sensitized solar cells since they
      bind more strongly to TiO(2) surfaces and form stable covalent bonds that are
      unaffected by humidity. Density functional theory calculations and quantum
      dynamics simulations of IET indicate that electron injection in 1-TiO(2) can be
      up to 1 order of magnitude faster when 1 is attached to TiO(2) in a bidentate
      mode (tau approximately 60 fs) than when attached in a monodentate motif (tau
      approximately 460 fs). The IET time scale also depends strongly on the properties
      of the sensitizer as well as on the nature of the electronic excitation initially
      localized in the adsorbate molecule. We show that IET triggered by the visible
      light excitation of 2-TiO(2) takes 1-10 ps when 2 is attached in a bidentate
      mode, a time comparable to the lifetime of the excited electronic state. IET due
      to visible-light photoexcitation of 3-TiO(2) is slower, since the resulting
      electronic excitation remains localized in the tpy-tpy bridge that is weakly
      coupled to the electronic states of the conduction band of TiO(2). These results
      are particularly valuable to elucidate the possible origin of IET efficiency
      drops during photoconversion in solar cells based on Ru(II)-polypyridine
      complexes covalently attached to TiO(2) thin films with phosphonate linkers.

PMID- 19594157
TI  - Vibrational modes of the vinyl and deuterated vinyl radicals.
AB  - Following the initial report of the detection of fundamental transitions of all
      nine vibrational modes of the vinyl radical [Letendre , L. ; Liu , D.-K. ; Pibel
      , C. D. ; Halpern , J. B. ; Dai , H.-L. J. Chem. Phys. 2000 , 112 , 9209] by time
      resolved IR emission spectroscopy, we have re-examined the assignments of the
      vibrational modes through isotope substitution. Precursor molecules vinyl
      chloride-d3, vinyl bromide-d3, and 1,3-butadiene-d6 are used for generating
      vibrationally excited vinyl-d3 through 193 nm photolysis. The nondeuterated
      versions of these molecules along with vinyl iodide and methyl vinyl ketone are
      used as precursors for the production of vinyl-h3. IR emission following the 193
      nm photolysis laser pulse is recorded with nanosecond time and approximately 8
      cm(-1) frequency resolution. A room-temperature acetylene gas cell is used as a
      filter to remove the fundamental transitions of acetylene, a photolysis product,
      in order to reduce the complexity of the emission spectra. Two-dimensional cross
      spectra correlation analysis is used to identify the emission bands from the same
      emitting species and improve the S/N of the emission spectra. Isotope
      substitution allows the identification of several low-frequency vibrational
      modes. For C2H3, the assigned modes are the nu4 (CC stretch) at 1595, nu5 (CH2
      symmetric bend) at 1401, nu6 (CH2 asymmetric + alpha-CH bend) at 1074, nu8 (CH2 +
      alpha-CH symmetric out-of-plane (oop) bend) at 944, and nu9 (CH2 + alpha-CH
      asymmetric oop bend) at 897 cm(-1). For C2D3, the modes are the nu5 (CD2
      symmetric bend) at 1060, nu6 (CD2 asymmetric + alpha-CD bend) at 820, and nu8
      (CD2 + alpha-CD symmetric oop bend) at 728 cm(-1).

PMID- 19594156
TI  - Vertical ionization energies of adenine and 9-methyl adenine.
AB  - Vertical ionization energies of 9-H adenine and 9-methyl adenine have been
      calculated with the following, ab initio, electron propagator methods: the outer
      valence Green's function (OVGF), partial third-order theory (P3), and the third
      order algebraic diagrammatic construction, or ADC(3). Basis set effects have been
      systematically examined. All methods predict near degeneracy in the pi(2)-n(1)
      and pi(3)-n(2) pairs of cationic, adenine final states and larger splittings of
      the corresponding, cationic states of 9-methyl adenine. P3 results for adenine
      predict the following order of the first six final states: pi(1), n(1), pi(2),
      n(2), pi(3), n(3). Coupled-cluster calculations on the first three cationic
      states of adenine confirm these predictions. OVGF and ADC(3) calculations reverse
      the order of the second and third states and of the fourth and fifth states. All
      results confirm previous interpretations of experiments in which the second and
      third spectral bands correspond to the aforementioned pairs of final states and
      disagree with a recent reassignment based on time-resolved photoelectron spectra.
      Lower ionization energies and larger splittings in the methylated molecule are
      interpreted in terms of phase relationships in the Dyson orbitals. ADC(3) results
      confirm the qualitative validity of the one-electron approximation for the first
      six final states of both molecules and disclose its inadequacies for higher
      ionization energies.

PMID- 19594158
TI  - Dough rheology and wet milling of hard waxy wheat flours.
AB  - To realize the full potential of waxy wheat (Triticum aestivum L.), the wet
      milling properties of waxy wheat flours including their dough-mixing properties
      were investigated. Flours of six waxy hard wheats, one normal hard wheat ('Karl
      92'), and one partial waxy hard wheat ('Trego') were fractionated by the dough
      washing (Martin) process, and the yields and recoveries of starch and gluten were
      compared. When waxy and normal wheat starches each were blended with a wheat
      gluten to give a mixture containing 14.5% protein, they gave very different
      mixograms even though the protein was the same in those blends. Waxy wheat starch
      absorbed more water than normal wheat starch, which apparently retarded hydration
      of gluten and dough development. Higher water content had to be used for some
      waxy wheat flours to develop optimum dough. Washing waxy wheat flour dough under
      a stream of water caused dough to become slack, spread out more on the sieve, and
      break apart into several pieces, which when thoroughly washed, coalesced into an
      elastic dough like the controls. By mixing a weak dough with 2% NaCl solution or
      by adding hemicellulase, stickiness of the dough subsided during the washing step
      and thereby improved the recovery of the gluten and starch fractions.

PMID- 19594159
TI  - Determination of N-glycosylation site and glycan structures of pectin
      methylesterase in jelly fig (Ficus awkeotsang) Achenes.
AB  - Pectin methylesterase (PME) in jelly fig (Ficus awkeotsang) achenes is an N
      glycosylated enzyme responsible for the gelation of jelly curd. A recombinant
      jelly fig PME was overexpressed in Escherichia coli and confirmed by
      immunodetection and LC-nanoESI-MS/MS analysis. To identify the N-glycosylation
      site, native PME and its deglycosylated and recombinant forms, which lacked
      glycan, were purified and subjected to comparative MALDI-MS mapping of the
      corresponding tryptic fragments. The results showed that N-glycosylation occurred
      at Asn(153) of the mature jelly fig PME, the only glycosylation site predicted by
      its sequence analysis. The major N-glycans released from the native PME by PNGase
      F were identified by MS/MS analyses as xylosylated, noncore fucosylated pauci
      mannose, and complex-type structures. Molecular modeling of the 3D structure of
      jelly fig PME indicated that the N-glycan was putatively attached to the back
      region of the active site of this enzyme.

PMID- 19594160
TI  - Ir doping-induced superconductivity in the SmFeAsO system.
AB  - The 5d transition metal Ir is successfully doped for Fe in SmFeAsO to induce
      superconductivity with T(c) = 16 K at a doping level of approximately 15 atom %.
      Ir doping decreases the As-Fe-As bond angle, beta; this behavior is different
      from the change in beta for the system with doping charges in the charge
      reservoir layers.

PMID- 19594161
TI  - Alternethanoxins A and B, polycyclic ethanones produced by Alternaria sonchi ,
      potential mycoherbicides for Sonchus arvensis biocontrol.
AB  - Alternaria sonchi is a fungal pathogen isolated from Sonchus arvensis and
      proposed as a biocontrol agent of this noxious perennial weed. Different
      phytotoxic metabolites were isolated from solid culture of the fungus. Two new
      polycyclic ethanones, named alternethanoxins A and B, were characterized using
      essentially spectroscopic and chemical methods. Tested by leaf disk-puncture
      assay on the fungal host plant and a number of nonhost plants, alternethanoxins A
      and B were shown to be phytotoxic, whereas they did not possess antimicrobial
      activity tested at 100 microg/disk. Hence, alternethanoxins A and B have
      potential as nonselective natural herbicides. Some structure-activity
      relationship observations were also made.

PMID- 19594162
TI  - Octanuclear copper(I) clusters inscribed in a Se(12) icosahedron: anion-induced
      modulation of the core size and symmetry.
AB  - Synthesis and structural characterization of an octanuclear Cu(I) cluster
      [Cu(8){Se(2)P(O(i)Pr)(2)}(6)](PF(6))(2) (1) with an empty Cu(8) cubic core
      involving diisopropyl diselenophosphate (dsep) ligand has been demonstrated
      despite its high tendency to abstract anions even from the traces of impurities
      in the solvent. Reaction of 1 with anion sources (Bu(4)NF for F(-); NaBH(4) for
      H(-), and NaSH for S(2-)) in a 1:1 ratio produced anion-centered Cu(8) clusters
      with a formula [Cu(8)(X){Se(2)P(O(i)Pr)(2)}(6)](PF(6)) (X = F, 2a; H, 3a; D, 3a')
      and [Cu(8)(S){Se(2)P(O(i)Pr)(2)}(6)] (4) in high yields. In addition, fluoride-
      and hydride-centered Cu(8)(I) clusters [Cu(8)(X){Se(2)P(OEt)(2)}(6)](PF(6)) (X =
      F, 2b; H, 3b) could be generated in approximately 80% yield by direct reaction of
      [Cu(CH(3)CN)(4)](PF(6)), NH(4)Se(2)P(OEt)(2), and the anion sources (Bu(4)NF for
      F(-); NaBH(4) for H(-)) in 8:6:1 ratio. Whereas the structural elucidation of
      complexes 2 and 4 revealed an anion-centered cubic Cu(8) core surrounded by six
      dsep ligands, it was a tetracapped tetrahedral copper framework with a hydride in
      the center in compounds 3. All Cu...Cu distances along either the edge of the
      cube in 2 and 4 or the tetracapped tetrahedron in 3 are shorter than those
      identified in 1. Although the cubic (or spherical) contraction of the copper
      framework that was identified in a series of closed-shell anion-centered (except
      a hydride) Cu(8) cube having T(h) symmetry could be explained by the existence of
      strong anion-cation attractions, it was definitely a surprise that the hydride,
      which is the smallest closed-shell anion and spherical too, induced a tetrahedral
      contraction of four out of the eight Cu atoms in the empty cube 1, resulting in a
      tetracapped-tetrahedral geometry and reducing the symmetry to T from T(h).
      Furthermore the fact that the encapsulated anion induced modulation of the copper
      core size and symmetry was fully reproduced by DFT calculations on model
      compounds. To the best of our knowledge, this demonstrated the first example of
      the reduction of molecular symmetry (from T(h) to T) simply by changing the
      encapsulated species without altering the general bonding pattern of the
      surrounding ligands. We also demonstrated that the hydride can easily replace
      other anions (Cl(-), Br(-), F(-), S(2-), Se(2-)) in a very facile manner to
      produce hydride-centered species. Eventually, compounds 3 were stable in the
      presence of other anions, and hydride/deuteride exchange could not be achieved.

PMID- 19594163
TI  - All-carbon quaternary centers via ruthenium-catalyzed hydroxymethylation of 2
      substituted butadienes mediated by formaldehyde: beyond hydroformylation.
AB  - Ruthenium-catalyzed transfer hydrogenation of 2-substituted dienes 1a-i in the
      presence of paraformaldehyde results in reductive coupling at the 2-position to
      furnish the hydroxymethylation products 3a-i, which embody all-carbon quaternary
      centers. Reductive coupling of diene 1g to paraformaldehyde under standard
      conditions, but employing deuterio-paraformaldehyde, 2-propanol-d(8), or both,
      corroborated a catalytic mechanism involving rapid, reversible diene
      hydrometalation with incomplete regioselectivity in advance of C-C coupling. The
      present method provides an alternative to the hydroformylation of conjugated
      dienes, for which efficient, regioselective catalytic systems remain undeveloped.

PMID- 19594164
TI  - Measurements of the carrier dynamics and terahertz response of oriented germanium
      nanowires using optical-pump terahertz-probe spectroscopy.
AB  - We have measured the terahertz response of oriented Germanium nanowires using
      ultrafast optical-pump terahertz-probe spectroscopy. We present results on the
      time, frequency, and polarization dependence of the terahertz response. Our
      results indicate intraband energy relaxation times of photoexcited carriers in
      the 1.5-2.0 ps range, carrier density dependent interband electron-hole
      recombination times in the 75-125 ps range, and carrier momentum scattering rates
      in the 60-90 fs range. Additionally, the terahertz response of the nanowires is
      strongly polarization dependent despite the subwavelength dimensions of the
      nanowires. The differential terahertz transmission is found to be large when the
      field is polarized parallel to the nanowires and very small when the field is
      polarized perpendicular to the nanowires. This polarization dependence of the
      terahertz response can be explained in terms of the induced depolarization fields
      and the resulting magnitudes of the surface plasmon frequencies.

PMID- 19594165
TI  - A concise Diels-Alder strategy for the asymmetric synthesis of (+)-albicanol, (+)
      albicanyl acetate, (+)-dihydrodrimenin, and (-)-dihydroisodrimeninol.
AB  - A short, mild, highly diastereo-, regio-, and stereoselective Diels-Alder
      strategy has been developed for the asymmetric synthesis of (+)-albicanol, (+)
      albicanyl acetate, (+)-dihydrodrimenin, and (-)-dihydroisodrimeninol.

PMID- 19594166
TI  - Bilayers as phase transfer agents for nanocrystals prepared in nonpolar solvents.
AB  - The effective water dispersion of highly uniform nanoparticles synthesized in
      organic solvents is a major issue for their broad applications. In an effort to
      overcome this problem, iron oxide and cadmium selenide nanocrystals were
      surrounded by lipid bilayers to create stable, aqueous dispersions. The core
      inorganic particles were originally generated in oleic acid and 1-octadecene.
      When these organic solutions were mixed with water and a sparing amount of excess
      fatty acid, up to 70% of the nanoparticles transferred into the aqueous phase.
      This simple approach was applied to two different nanocrystal types, and
      nanocrystal diameters ranging from 5 to 15 nm. In all cases, the resulting
      materials were stable, nonaggregated suspensions that retained their original
      magnetic and optical properties. The phase transfer efficiency is maximum when
      very little oleic acid is added (e.g. 0.2 w/w %). At higher concentrations, above
      the critical micelle concentration, the formation of micelles begins to compete
      with bilayer generation leading to less effective phase transfer. Unlike other
      approaches for water dispersion that rely on amphiphiles with significant water
      solubility, the fatty acids used in this work are only sparingly soluble in
      water. As a result, there is minimal dynamic exchange between free and bound
      surface agents and the resulting aqueous solutions contain little residual free
      organic carbon. Thermogravimetric analysis (TGA) confirmed the presence of
      bilayers around the nanocrystal cores. The particle size, size distribution,
      process yield, and colloidal stability were found using a suite of methods
      including transmission electron microscopy, small angle X-ray scattering, dynamic
      light scattering, inductively coupled plasma-optical emission spectroscopy, and
      ultraviolet-visible spectroscopy. Bilayer-nanocrystal complexes possess many of
      the same size-dependent features as the original materials, and as such offer new
      avenues for exploring and exploiting the interface between nanocrystals and
      biology.

PMID- 19594167
TI  - sp2-sp3 hybridized mixed diboron: synthesis, characterization, and copper
      catalyzed beta-boration of alpha,beta-unsaturated conjugated compounds.
AB  - A novel sp(2)-sp(3) hybridized mixed diboron and its reactivity on the copper
      catalyzed beta-boration of alpha,beta-unsaturated conjugated compounds to afford
      the corresponding beta-borated compounds is reported. The presence of sp(3)
      hybridized boron provides a mild beta-boration condition in the absence of
      phosphine and base additives. Finally, our investigations demonstrate that the
      sp(2)-hybridized boron of the mixed diboron is selectively transferred to the
      beta-carbon of conjugated substrates.

PMID- 19594168
TI  - Thermodynamic characterization of the exchange of detergents and amphipols at the
      surfaces of integral membrane proteins.
AB  - The aggregation of integral membrane proteins (IMPs) in aqueous media is a
      significant concern for mechanistic investigations and pharmaceutical
      applications of this important class of proteins. Complexation of IMPs with
      amphiphiles, either detergents or short amphiphilic polymers known as amphipols
      (APols), renders IMPs water-soluble. It is common knowledge that IMP-detergent
      complexes are labile, while IMP-APol complexes are exceptionally stable and do
      not dissociate even under conditions of extreme dilution. To understand the
      thermodynamic origin of this difference in stability and to guide the design of
      new APols, we have studied by isothermal titration calorimetry (ITC) the heat
      exchanges during two reciprocal processes, the "trapping" of detergent
      solubilized IMPs in APols and the "stripping" of IMP-APol complexes by
      detergents, using two IMPs (the transmembrane domain of porin OmpA from
      Escherichia coli and bacteriorhodopsin from Halobium salinarium), two APols [an
      anionic polymer derived from acrylic acid (A8-35) and a cationic
      phosphorylcholine-based polymer (C22-43)], and two neutral detergents [n-octyl
      thioglucoside (OTG) and n-octyltetraethylene glycol (C(8)E(4))]. In the presence
      of detergent, free APols and IMP-APol complexes form mixed particles, APol
      detergent and IMP-APol-detergent, respectively, according to the regular mixing
      model. Diluting IMP-APol-detergent complexes below the critical micellar
      concentration (CMC) of the detergent triggers the dispersion of detergent
      molecules as monomers, a process characterized by an enthalpy of demicellization.
      The enthalpy of APol <--> detergent exchange on the hydrophobic surface of IMPs
      is negligibly small, an indication of the similarity of the molecular
      interactions of IMPs with the two types of amphiphiles. The enhanced stability
      against dilution of IMP-APol complexes, compared to IMP-detergent ones,
      originates from the difference in entropy gain achieved upon release in water of
      a few APol molecules (in the case of IMP-APol complexes) or several hundred
      detergent molecules (in the case of IMP-detergent complexes). The data account
      both for the stability of IMP-APols complexes in the absence of detergent and for
      the ease with which detergents displace APols from the surface of proteins.

PMID- 19594169
TI  - The 1.85 A structure of an 8R-lipoxygenase suggests a general model for
      lipoxygenase product specificity.
AB  - Lipoxygenases (LOX) play pivotal roles in the biosynthesis of leukotrienes and
      other biologically active eicosanoids derived from arachidonic acid. A
      mechanistic understanding of substrate recognition, when lipoxygenases that
      recognize the same substrate generate different products, can be used to help
      guide the design of enzyme-specific inhibitors. We report here the 1.85 A
      resolution structure of an 8R-lipoxygenase from Plexaura homomalla, an enzyme
      with a sequence approximately 40% identical to that of human 5-LOX. The structure
      reveals a U-shaped channel, defined by invariant amino acids, that would allow
      substrate access to the catalytic iron. We demonstrate that mutations within the
      channel significantly impact enzyme activity and propose a novel model for
      substrate binding potentially applicable to other members of this enzyme family.

PMID- 19594170
TI  - Acrylamide quenching of Trp phosphorescence in liver alcohol dehydrogenase:
      evidence of gated quencher penetration.
AB  - Notwithstanding the relevance of their biological function, slow motions in
      proteins, beyond the microsecond range, are still poorly understood and often
      elusive. We propose that acrylamide quenching of Trp phosphorescence of deeply
      buried residues, when extended over the entire accessible range of lifetime
      measurements (tau > 10 micros), may help to unveil low-frequency protein motions
      that allow penetration of solute into the protein interior. The work examines in
      some detail acrylamide quenching of Trp phosphorescence in a model protein (liver
      alcohol dehydrogenase) over an extended submillimolar to molar acrylamide
      concentration range. The results, which encompass a >10(4)-fold variation in the
      quenching rate, provide the first evidence of a downward-curving lifetime Stern
      Volmer plot, indicative of a nonlinear dependence of the quenching rate on the
      quencher concentration. From an analysis of saturation effects in terms of a
      protein-gated acrylamide diffusion mechanism, we infer two main routes for
      acrylamide to penetrate the globular fold and come into the proximity of internal
      W314: a low-frequency gate [36 s(-1) (at 25 degrees C)] tentatively assigned to
      partial opening of the dimer interface and a higher-frequency one (11800 s(-1))
      tentatively assigned to a channel blocked by the side chains of V276 and L307.
      These motions are sharply inhibited in the rigid protein complexes formed with
      the coenzyme NAD(+) and the coenzyme analogue adenine diphosphate ribose, as well
      as by the frictional drag of the solvent in viscous glycerol solutions, evidence
      that rules out an alternative quenching mechanism involving acrylamide binding to
      the protein.

PMID- 19594172
TI  - Ionic-complementary peptide matrix for enzyme immobilization and biomolecular
      sensing.
AB  - A novel electrochemical biosensing platform is described using biocompatible,
      self-assembled ionic-complementary peptide nanofibers. The compatibility of a
      graphite electrode modified by these peptide nanofibers with enzymes is
      demonstrated using a model enzyme glucose oxidase (GOx). A glucose biosensor has
      been successfully fabricated by incorporating this enzyme into the modified
      electrode. From measurement of its electrode response and sensitivity, this
      nanofiber-modified electrode shows promise as an enzyme-based biosensor. The
      findings presented here demonstrate excellent potential of the use of ionic
      complementary peptides to modify electrode surfaces for biomolecular sensing and
      diagnostics.

PMID- 19594173
TI  - Preparation and electrochemical performance of novel ordered mesoporous carbon
      with an interconnected channel structure.
AB  - A novel ordered mesoporous carbon with an interconnected channel structure (OMC
      IC) has been successfully fabricated by adding proper hydrophilic SiO(2)
      nanoparticles to the solution of triblock copolymer F127 and phenol-formaldehyde
      resol. Experimental results show that the presence of SiO(2) nanoparticles does
      not hamper the self-assembly of F127 and resol to form an ordered two-dimensional
      hexagonal mesostructure. The neighboring channels of the OMC-IC are
      interconnected after removing SiO(2) nanoparticles with a diameter larger than
      the thickness of the carbon wall. Such an interconnectivity of channels is
      beneficial in improving ion diffusion properties. The as-prepared OMC-IC exhibits
      much lower impedance to ion transport within both the channels and the micropores
      in the carbon wall, and thus has better electric double layer performance as
      compared to the conventional OMC with an unconnected channel structure.

PMID- 19594171
TI  - Guanidine hydrochloride-induced unfolding of the three heme coordination states
      of the CO-sensing transcription factor, CooA.
AB  - CooA is a heme-dependent CO-sensing transcription factor that has three
      observable heme coordination states. There is some evidence that each CooA heme
      state has a distinct protein conformation; the goal of this study was to
      characterize these conformations by measuring their structural stabilities
      through guanidine hydrochloride (GuHCl) denaturation. By studying the
      denaturation processes of the Fe(III) state of WT CooA and several variants, we
      were able to characterize independent unfolding processes for each domain of
      CooA. This information was used to compare the unfolding profiles of various CooA
      heme activation states [Fe(III), Fe(II), and Fe(II)-CO] to show that the heme
      coordination state changes the stability of the effector binding domain. A
      mechanism consistent with the data predicts that all CooA coordination states and
      variants undergo unfolding of the DNA-binding domain between 2 and 3 M GuHCl with
      a free energy of unfolding of approximately 17 kJ/mol, while unfolding of the
      heme domain is variable and dependent on the heme coordination state. The
      findings support a model in which changes in heme ligation alter the structural
      stability of the heme domain and dimer interface but do not alter the stability
      of the DNA-binding domain. These studies provide evidence that the domains of
      transcription factors are modular and that allosteric signaling occurs through
      changes in the relative positions of the protein domains without affecting the
      structure of the DNA-binding region.

PMID- 19594174
TI  - Lysine-bisglycidol conjugates as novel lysine cationic surfactants.
AB  - The synthesis of a novel class of lysine-based cationic amphiphilic derivatives
      of the type N(epsilon),N(epsilon)'-bis(n-acyloxypropyl)-l-lysine methyl ester
      salts combining several hydroxyl functions and aliphatic chains of 12 or 14
      carbon atoms is described. The compounds have one, two, three, and four alkyl
      chains. Aggregation in water was studied by four different methods: surface
      tension, conductivity, chloride ion activity, and nuclear magnetic resonance
      ((1)H NMR). The critical aggregation concentration value of the new surfactants
      depends on both the number of alkyl chains and the alkyl chain length. The
      formation of vesicles at low concentrations was confirmed by H(1) NMR and optical
      microscopy. Antimicrobial activity was determined on the basis of the minimum
      inhibitory concentration (MIC) values. These novel lysine-based surfactants
      showed moderate antimicrobial activity which may be an important advantage for
      many biomedical applications.

PMID- 19594175
TI  - Ordering in two-dimensional dipolar mixtures.
AB  - Two-dimensional dipolar mixtures consisting of spherical particles with unequal
      susceptibilities are shown to order to an enormous variety of crystalline
      structures, whose geometry can be tuned by the stoichiometry of the compound, the
      susceptibility ratio, as well as the density. Our results are based on the
      application of genetic algorithms, which allow for an efficient and unbiased
      search over the parameter space. Structures that are practically degenerate
      energetically are discovered at various parameter combinations. Implications on
      the ability to tune the phononic spectra of such composite materials are
      discussed.

PMID- 19594176
TI  - Foam drainage in the presence of nanoparticle-surfactant mixtures.
AB  - The drainage of SiO(2) nanoparticle-cationic surfactant (TTAB) mixtures through
      calibrated aqueous foams had been studied by combining several approaches on both
      the macroscopic and the local scale. Macroscopic measurements reveal a strong
      stabilizing effect arising for nanoparticle concentrations as low as 2 wt %
      mainly because of a drainage kinetic slow-down dependent on the nanoparticle
      concentration. We show that the variation of the viscous parameters (bulk
      viscosity, interfacial viscosity, or both) in the classical theoretical models of
      foam drainage, mainly developed for aqueous surfactant solutions, does not enable
      fitting experimental data obtained via steady- or free-drainage strategies for
      [SiO(2)] > or = 2 wt %. In contrast, the quantitative analysis of the data
      obtained from front propagation velocities has revealed a drainage regime
      transition from a node-dominated regime toward a Plateau-border-dominated regime
      upon nanoparticle concentration increase. Observations performed at the Plateau
      border scale brought to light the drainage kinetic slow-down process by
      evidencing that the presence of insoluble aggregates induces traffic jamming and
      even cork formation for silica concentrations above 2 wt %. Considering these
      observations, a simple mechanism of aggregate growth and cork formation is
      proposed. Finally, we analyze the discrepancy between experiments (steady- and
      free-drainage methods) and theory by pointing out that the hypothesis relative to
      the foam structure that is usually assumed for both the liquid fraction
      calculation and the determination via conductivity measurements is strongly
      modified when large insoluble aggregates are present in the system. In this view,
      the method based on the liquid fraction determination through the measurement of
      the front propagation velocity seems to be the most suitable for studying the
      drainage of colloidal dispersion because of the lower dependence of this approach
      toward hypothesis on the local geometry of the foam continuous phase.

PMID- 19594177
TI  - Synthesizing microcapsules with controlled geometrical and mechanical properties
      with microfluidic double emulsion technology.
AB  - Using lithography-based microfluidic technology, we produce monodisperse single
      core microcapsules with UV-cured TPGDA (triprophylene glycol diacrylate) shells.
      We show that the geometrical and mechanical characteristics of the microcapsules
      can be predicted on a quantitative basis and tuned by varying the flow
      conditions. Shell thicknesses are varied by changing the flow rates of the inner
      or intermediate phases, according to mass conservation constraint. Off-centering
      of the core with respect to the shell is controlled by varying the shell phase
      viscosity. The mechanical properties of the capsules can be varied by changing
      the flow conditions and are quantitatively predicted by a numerical simulation.
      The simulation moreover provides a correct qualitative description of their
      rupture. As a whole, the work carried out in the present paper shows, on a
      quantitative basis, that microfluidic technology allows to finely control the
      geometrical and mechanical properties of microcapsules generated on chip. The
      level of control we reach here is not accessible, by far, to conventional
      technologies. Combined with parallelization, the present work opens routes toward
      the production of novel families of monodisperse microcapsules with tunable
      properties.

PMID- 19594178
TI  - Multiscale characterization of individualized beta-lactoglobulin microgels formed
      upon heat treatment under narrow pH range conditions.
AB  - Aqueous dispersions of demineralized beta-lactoglobulin (beta-lg) were held at 85
      degrees C for 15 min at a constant protein concentration of 1 wt % in the pH
      range of 3.0-7.0. This led to denatured protein content ranging from 20% (pH 3.0)
      to 90% (pH 5.0). The protein aggregates formed were characterized as to their
      stability to sedimentation (turbidity), morphology, size, surface charge, ANS
      surface hydrophobicity, and content in accessible thiol groups. Additionally, the
      changes in secondary structures of the protein upon heating were followed by
      Fourier transform infrared spectroscopy (FTIR). Stable dispersions (no
      sedimentation for 10 min) of individualized beta-lg microgels were obtained at
      specific pH 4.6 and 5.8, corresponding to an aggregation yield of about 80%. The
      width of the pH region leading to these microgels was 0.3 pH unit below or above
      the two specific pH values. Microgels were characterized by a spherical shape and
      remarkably low polydispersity in size (<0.2). Their z-average hydrodynamic
      diameter determined by dynamic light scattering (DLS) was between 160 and 220 nm,
      and their zeta-potential was +30 or -40 mV, depending on the initial pH before
      heating. Microgels obtained at pH 4.6 displayed a lower binding capacity for ANS
      and a lower content of accessible thiol groups as compared to those obtained at
      pH 5.8. Both types of microgels might therefore differ in their internal and
      interfacial structures. Between pH 4.6 and 5.8, large sedimenting protein
      particulates were obtained, whereas soluble aggregates were formed at pH <4.6 or
      >5.8. Interestingly, DLS experiments showed that before heating, beta-lg was
      mainly present in an oligomeric state at pH 4.6 and 5.8. This result was
      confirmed by FTIR measurements indicating the stronger contribution of the 1616
      1624 cm(-1) spectral band corresponding to intermolecular beta-sheets in the pH
      range of 4.0-6.0. Upon heating, FTIR spectroscopy revealed that individualized
      microgels were obtained under pH conditions where a balance between attractive
      forces arising from protein unfolding leading to the formation of intermolecular
      beta-sheets (1616-1624 cm(-1 )band) and the repulsive electrostatic forces due to
      the initial protein net charge was achieved.

PMID- 19594179
TI  - alpha-lactalbumin-AOT charge interactions tune phase structures in
      isooctane/brine mixtures.
AB  - Self-assembly of the anionic surfactant AOT with the protein alpha-lactalbumin in
      isooctane/brine mixtures results in phase structures whose type, size, and shape
      differ considerably from those formed by the surfactant alone. Small-angle X-ray
      scattering was used to determine the size and shape of these structures for 5.4 <
      pH < 11.2 and 0.25, 0.33, and 0.4 wt % NaCl. All pH values were above the
      reported isoelectric point for the protein. The composition of the system (except
      for salt) was fixed, with 2.5 wt % surfactant in equivolume mixtures of oil and
      water and either 0 or 0.4 wt % protein. Under these conditions, AOT in the
      absence of protein always formed spherical, water-in-oil (w/o) microemulsion
      droplets in the organic phase with no self-assembly in the aqueous phase. In the
      presence of alpha-lactalbumin, self-assembled structures were formed in both
      aqueous and organic phases, and the size and shape of these was tuned by both pH
      and [NaCl]. Protein-surfactant interaction was weakest at the most alkaline pH,
      with protein-free, spherical droplets forming in the organic phase and surfactant
      decorated soluble protein clusters forming in the aqueous phase. As pH was
      decreased, protein increasingly partitioned to the organic phase and droplets
      became ellipsoidal and much larger in volume, with these effects enhanced at
      lower salt concentration. Aqueous structures were also strongly affected by pH,
      shifting from prolate protein/surfactant aggregates at alkaline pH to oil-in
      water, oblate microemulsion droplets at neutral pH. At acidic pH and higher salt
      concentration, self-assembly shifted toward a third, anisotropic aqueous phase,
      which contained discoid bilayer structures. It is proposed that hydrophobic
      attraction causes association of the protein with the surfactant monolayer, and
      pH and [salt] tune the system via the protein by modifying electrostatic
      repulsion and monolayer curvature.

PMID- 19594181
TI  - Preparation and characterization of silver substrates coated with antimony-doped
      SnO2 thin films for surface plasmon resonance studies.
AB  - This paper reports on the preparation of silver/antimony-doped tin oxide
      (Ag/SnO(2):Sb) hybrid interfaces using magnetron sputtering and their
      characterization. The influence of the Sn target composition (doping with 2 or 5%
      Sb) on the electrochemical and electrical characteristics of the hybrid interface
      was investigated using X-ray photoelectron spectroscopy (XPS), sheet resistance
      measurements, cyclic voltammetry, scanning tunneling microscopy (STM) and surface
      plasmon resonance (SPR). The best interface in terms of electrical conductivity
      and SPR signal is a hybrid interface with a 8.5 +/- 0.3 nm thick SnO(2):Sb layer
      obtained from a Sn target with 2% Sb deposited on 38 nm thick silver film.
      Different strategies to link functional groups onto the Ag/SnO(2):Sb interface
      are also presented.

PMID- 19594180
TI  - Interfacial hydrodynamic drag on nanowires embedded in thin oil films and protein
      layers.
AB  - We investigate the motion of ferromagnetic nanowires confined to nanometer-scale
      oil films at an air/aqueous interface in response to the application of external
      magnetic fields and field gradients. By varying the oil viscosity, film
      thickness, and wire length, we cover two regimes of response suggested by theory:
      one where the surface viscosity is expected to dominate the wire's motion and one
      where the subphase viscosity is expected to dominate [Levine, A. J.; Liverpool,
      T. B.; MacKintosh, F. C. Phys. Rev. E 2004, 69, 021503]. For wire motion parallel
      to the long axis of the wire, the observed drag agrees reasonably with
      theoretical predictions. However, the drag on wires moving perpendicular to their
      long axis or rotating about a short axis is unexpectedly insensitive to the film
      properties over the full range of measurements. This behavior is in contrast to
      the rotational and translational drag on nanowires in molecularly thin protein
      layers, which follow theoretical expectations. The observations in the oil films,
      which are explained in terms of the manner in which the wire immerses dynamically
      in the film and subphase, demonstrate how the effective drag viscosity of an
      aspherical particle confined to a fluid interface can depend on its direction of
      motion.

PMID- 19594182
TI  - Gas barrier film with a compositional gradient interface prepared by plasma
      modification of an organic/inorganic hybrid sol-gel coat.
AB  - A high-performance gas barrier film has been prepared using a simple oxygen
      plasma treatment of an organic/inorganic hybrid sol-gel coat on a poly(ether
      sulfone) substrate. The gas barrier layer formed from the plasma treatment was an
      inorganic silicon oxide (SiO(x)) having a compositional gradient interface with
      the sol-gel coat, where the chemical compositions changed gradually from
      inorganic to organic structure at the interface. The minimum attained oxygen
      transmission rate (OTR) of the gas barrier layer was 0.2 cm(3)/(m(2) day), which
      is superior or comparable to that of the gas barrier layer prepared by plasma
      enhanced chemical vapor deposition (PECVD) or sputtering. Low-temperature oxygen
      plasma combustion of alkyl groups existing in the sol-gel coat is considered to
      be the major reaction for the formation of the SiO(x) gas barrier layer, where
      oxygenated carbon compounds and hydrogen were the main volatile components as
      verified by the analysis of optical emission spectroscopy. Plasma treatment time
      necessary to attain a high-performance SiO(x) gas barrier layer decreased with
      increasing RF plasma power. In a dynamic bending test, the gas barrier film
      preserved the initial gas barrier properties without any formation of film cracks
      or delamination. The compositional gradient at the interface between the gas
      barrier and the sol-gel coat is considered to provide a stress-relieving effect
      at the interface.

PMID- 19594183
TI  - Correlating linactant efficiency and self-assembly: structural basis of line
      activity in molecular monolayers.
AB  - Surfactants exhibit characteristic phenomena, including the reduction of
      interfacial free energy, self-assembly into aggregates, and even the formation of
      lyotropic liquid crystalline phases at high concentrations. Our research has
      shown that a semifluorinated phosphonic acid can act as the two-dimensional
      analogue of a surfactant-a linactant-by reducing the line tension between
      hydrocarbon-rich and fluorocarbon-rich phases in a Langmuir monolayer. This
      linactant can also self-assemble into nanoscale clusters in a monolayer. Here, we
      explore the dependence of linactant behavior on molecular structure. Members of a
      homologous series of partially fluorinated phosphonic acids were synthesized and
      tested as linactants: CF(3)(CF(2))(n-1)(CH(2))(m)PO(3)H (abbreviated as
      FnHmPO(3)). The tests revealed that linactants with longer hydrophobic chains
      were most efficient in lowering line tension. For linactants with the same
      overall chain length, the length of the fluorocarbon block was correlated with
      efficiency. Thus, the linactant efficiency was ranked in the order F8H8PO(3) <
      F10H6PO(3) < F8H11PO(3) < F10H9PO(3). In all cases, linactant-containing Langmuir
      Blodgett monolayers exhibited nanoscale molecular clusters with characteristic
      dimensions of 20-30 nm; enhanced linactant efficiency was systematically
      correlated with larger clusters.

PMID- 19594184
TI  - Influence of elastic strains on the adsorption process in porous materials: an
      experimental approach.
AB  - The experimental results presented in this paper show the influence of the
      elastic deformation of porous solids on the adsorption process. With p(+)-type
      porous silicon formed on highly boron doped (100) Si single crystal, we can make
      identical porous layers, either supported by or detached from the substrate. The
      pores are perpendicular to the substrate. The adsorption isotherms corresponding
      to these two layers are distinct. In the region preceding capillary condensation,
      the adsorbed amount is lower for the membrane than for the supported layer and
      the hysteresis loop is observed at higher pressure. We attribute this phenomenon
      to different elastic strains undergone by the two layers during the adsorption
      process. For the supported layer, the planes perpendicular to the substrate are
      constrained to have the same interatomic spacing as that of the substrate so that
      the elastic deformation is unilateral, at an atomic scale, and along the pore
      axis. When the substrate is removed, tridimensional deformations occur and the
      porous system can find a new configuration for the solid atoms which decreases
      the free energy of the system adsorbate-solid. This results in a decrease of the
      adsorbed amount and in an increase of the condensation pressure. The isotherms
      for the supported porous layers shift toward that of the membrane when the layer
      thickness is increased from 30 to 100 mum. This is due to the relaxation of the
      stress exerted by the substrate as a result of the breaking of Si-Si bonds at the
      interface between the substrate and the porous layer. The membrane is the relaxed
      state of the supported layer.

PMID- 19594185
TI  - Electrophoretic study of the SnO2/aqueous solution interface up to 260 degrees C.
AB  - An electrophoresis cell developed in our laboratory was utilized to determine the
      zeta potential at the SnO(2) (cassiterite)/aqueous solution (10(-3) mol kg(-1)
      NaCl) interface over the temperature range from 25 to 260 degrees C. Experimental
      techniques and methods for the calculation of zeta potential at elevated
      temperature are described. From the obtained zeta potential data as a function of
      pH, the isoelectric points (IEPs) of SnO(2) were obtained for the first time.
      From these IEP values, the standard thermodynamic functions were calculated for
      the protonation-deprotonation equilibrium at the SnO(2) surface, using the 1-pK
      surface complexation model. It was found that the IEP values for SnO(2) decrease
      with increasing temperature, and this behavior is compared to the predicted
      values by the multisite complexation (MUSIC) model and other semitheoretical
      treatments, and were found to be in excellent agreement.

PMID- 19594186
TI  - Aggregation of amyloidogenic peptides near hydrophobic and hydrophilic surfaces.
AB  - The general effect of surface hydrophobicity/hydrophilicity on the aggregation of
      peptides is studied by simulations of oversaturated aqueous solutions of
      hydrophobic and hydrophilic amyloidogenic peptides. Peptide aggregation was
      studied in bulk solution, in solutions confined between hydrophobic boundaries
      (smooth planar paraffin-like surfaces and liquid-vapor interfaces) and in
      solutions confined between hydrophilic surfaces (smooth planar silica-like
      surfaces). Aggregation of hydrophobic peptides strongly enhances due to the
      confinement between hydrophobic surfaces with all peptides adsorbed at the
      boundaries and aligned predominantly parallel to them. In the other three cases
      considered, the peptides are repelled from the walls and do not reveal
      orientational ordering with respect to the surface. The degree of peptide
      aggregation in these cases is only slightly affected by the confinement (it is
      enhanced for hydrophobic peptides and decreased for hydrophilic peptides). Our
      results show that even a single environmental factor such as water-mediated
      peptide-surface interaction has a drastic effect on the degree and character of
      peptide aggregation. A wide diversity of possible scenarios can be expected when
      specific peptide-surface interactions are additionally taken into account.

PMID- 19594188
TI  - Preparation of stable exfoliated Pt-clay nanocatalyst.
AB  - In this paper, we report a novel experimental protocol for the preparation of
      stable and exfoliated nano-Pt catalysts supported on layered silicate clay
      surfaces. Uniformly dispersed highly crystalline Pt nanoparticles with diameters
      between 2 and 5 nm were chemically adsorbed on to the layered silicate surfaces
      using a chemical vapor deposition (CVD) method employing organoclay as the
      initial support. The as-prepared catalysts were found to be extremely stable
      against both intensive mechanical agitation and high temperature treatment. No Pt
      loading or morphology changes were observed after ultrasonication under a
      sonication power density of 6 MW/m(3) for up to 72 h at room temperature or
      annealing at 700 degrees C for 1 h under Ar flow. On the other hand, Pt catalysts
      prepared using the inorganic clay as the initial support were found to be highly
      unstable against both mechanical agitation and high temperature treatment.
      Significant leaching and catalyst restructuring or sintering was observed.
      Exfoliation of catalysts and the nature of Pt adsorption were elucidated by
      systematic analysis using wide-angle X-ray diffraction (WAXD) analysis, Brunauer
      Emmett-Teller (BET) surface area analysis, and time-of-flight secondary ion mass
      spectroscopy (ToF-SIMS) analysis. No low angle diffraction peak was observed in
      the WAXD pattern, and a 700% increase in BET surface area was observed after Pt
      deposition on clay surfaces. Depth profiling ToF-SIMS on Pt deposited on SiO(2)
      wafer surfaces showed the presence of PtSiO ion at the Pt and SiO(2) interface.
      This ion group was also detected in the bulk of Pt-OrC catalyst, confirming
      chemisorption of Pt on layered silicate clays. A much lower concentration of
      PtSiO ion was observed in the Pt-NaC with a similar Pt loading. In addition, X
      ray photoelectron spectroscopy (XPS) shows that the binding energy of Pt4f(7/2)
      in Pt-OrC is much higher than that in the Pt-NaC. The protocol reported in this
      paper can also be applicable to other clay supported stable metallic catalysts.

PMID- 19594187
TI  - pH-dependent formation of lipid heterogeneities controls surface topography and
      binding reactivity in functionalized bilayers.
AB  - During direct cell-to-cell communication, lipids on the extracellular side of
      plasma membranes reorganize, and membrane-associated communication-related
      molecules colocalize. At colocalization sites, sometimes identified as rafts, the
      local cell surface topography and reactivity are altered. The processes
      regulating these changes are largely unknown. On model lipid membranes, study of
      simplified processes that control surface topography and reactivity may
      potentially contribute to the understanding and control of related cell functions
      and associated diseases. Integration of these processes on nanometer-sized lipid
      vesicles used as drug delivery carriers would precisely control their
      interactions with diseased cells minimizing toxicities. Here we design such basic
      pH-dependent processes on model functionalized lipid bilayers, and we demonstrate
      reversible sharp changes in binding reactivity within a narrow pH window.
      Cholesterol enables tuning of the membrane reorganization to occur at pH values
      not necessarily close to the reported pK(a)'s of the constituent titratable
      lipids, and bilayer reorganization over repeated cycles of induced pH changes
      exhibits hysteresis.

PMID- 19594189
TI  - Rapid characterization of agglomerate aerosols by in situ mass-mobility
      measurements.
AB  - Transport and physical/chemical properties of nanoparticle agglomerates depend on
      primary particle size and agglomerate structure (size, fractal dimension, and
      dynamic shape factor). This research reports on in situ techniques for measuring
      such properties. Nanoparticle agglomerates of silica were generated by oxidizing
      hexamethyldisiloxane in a methane/oxygen diffusion flame. Upon leaving the flame,
      agglomerates of known electrical mobility size were selected with a differential
      mobility analyzer (DMA), and their mass was measured with an aerosol particle
      mass analyzer (APM), resulting in their mass fractal dimension, D(f), and dynamic
      shape factor, chi. Scanning and transmission electron microscopy (SEM/TEM) images
      were used to determine primary particle diameter and to qualitatively investigate
      agglomerate morphology. The DMA-APM measurements were reproducible within 5%, as
      determined by multiple measurements on different days under the same flame
      conditions. The effects of flame process variables (oxygen flow rate and mass
      production rate) on particle characteristics (D(f), and chi) were determined. All
      generated particles were fractal-like agglomerates with average primary particle
      diameters of 12-93 nm and D(f) = 1.7-2.4. Increasing the oxygen flow rate
      decreased primary particle size and D(f), while it increased chi. Increasing the
      production rate increased the agglomerate and primary particle sizes, and
      decreased chi without affecting D(f). The effects of oxygen flow rate and
      particle production rate on primary particle size reported here are in agreement
      with ex situ measurements in the literature, while the effect of process
      variables on agglomerate shape (chi) is demonstrated for the first time to our
      knowledge.

PMID- 19594190
TI  - Domain size manipulation of perflouorinated polymer electrolytes by sulfonic acid
      functionalized MWCNTs to enhance fuel cell performance.
AB  - The application of sulfonic acid-functionalized multiwalled (s-MWNT) carbon
      nanotubes to manipulate the hydrophilic domain size of Nafion membranes is
      explored here as an option for tuning the proton conductivity of polymer
      electrolyte membranes for hydrogen-oxygen fuel cells. The electrochemical
      impedance experiments provide preliminary evidence of increased proton
      conductivity, while small-angle X-ray scattering measurements line out enhanced
      ionic cluster domain size in these composite membranes as the central reason for
      higher conductivity (70 A for the optimum composite membrane vs 50 A for Nafion
      115) values. Scanning electrochemical microscopy indicates synergistic
      interaction between the sulfonic acid functional groups present in the Nafion
      membrane and those on the nanotube surface. More interestingly, the nanotube
      tailored Nafion membranes ameliorate the performance of fuel cells as confirmed
      by measurements at a single-cell level, which reveal a maximum power density of
      380 mW cm(-2), higher than those of Nafion 115 (250 mW cm(-2)) and recast Nafion
      (230 mW cm(-2)) membranes. Thus, in addition to providing an elegant means of
      controlling the ionic cluster size, the strategic approach of using CNT both as
      an anchoring backbone for -SO(3)H groups to enrich proton conductivity and as a
      blending agent to improve the mechanical characteristics of the Nafion phase
      might be helpful in alleviating many critical problems associated with the use of
      commercial Nafion membranes.

PMID- 19594191
TI  - Nanostructuring cadmium germanate catalysts for photocatalytic oxidation of
      benzene at ambient conditions.
AB  - A nanostructured Cd(2)Ge(2)O(6) photocatalyst was successfully prepared by a
      hydrothermal process. The photocatalyst was characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), UV/vis, N(2) adsorption-desorption, and Fourier transform infrared (FTIR)
      techniques. The photocatalytic property of the material was evaluated via the
      decomposition of benzene in the gas phase with light illumination and was
      compared with that of commercial titania (Degussa P25) and Pt/TiO(2). The
      electronic band structure of Cd(2)Ge(2)O(6) was analyzed by density functional
      theory (DFT) calculation. Results reveal that the prepared Cd(2)Ge(2)O(6) has
      unique geometric and electronic properties, which in combination with its
      superior textural properties makes it a new semiconductor photocatalyst for
      environmental purification of benzene in air with molecular oxygen under ambient
      conditions. It was also found that the Cd(2)Ge(2)O(6) was more active and stable
      than TiO(2)-based catalysts in the photocatalytic decomposition of other volatile
      aromatic pollutants including toluene and ethylbenzene. The enhanced
      photocatalytic performance of Cd(2)Ge(2)O(6) can be explained by the special band
      structure, and geometric and electronic feature, in unison with the high surface
      area nanoporous framework.

PMID- 19594192
TI  - Modeling the corrugation of the three-phase contact line perpendicular to a
      chemically striped substrate.
AB  - We model an infinitely long liquid bridge confined between two plates chemically
      patterned by stripes of the same width and different contact angle, where the
      three-phase contact line runs, on average, perpendicular to the stripes. This
      allows us to study the corrugation of a contact line in the absence of pinning.
      We find that, if the spacing between the plates is large compared to the length
      scale of the surface patterning, the cosine of the macroscopic contact angle
      corresponds to an average of cosines of the intrinsic angles of the stripes, as
      predicted by the Cassie equation. If, however, the spacing becomes on the order
      of the length scale of the pattern, there is a sharp crossover to a regime where
      the macroscopic contact angle varies between the intrinsic contact angle of each
      stripe, as predicted by the local Young equation. The results are obtained using
      two numerical methods, lattice Boltzmann (a diffuse interface approach) and
      Surface Evolver (a sharp interface approach), thus giving a direct comparison of
      two popular numerical approaches to calculating drop shapes when applied to a
      nontrivial contact line problem. We find that the two methods give consistent
      results if we take into account a line tension in the free energy. In the lattice
      Boltzmann approach, the line tension arises from discretization effects at the
      diffuse three phase contact line.

PMID- 19594194
TI  - The CATIE and CUtLASS studies in schizophrenia: results and implications for
      clinicians.
AB  - Numerous double-blind studies have compared second-generation antipsychotics
      (SGAs) with first-generation antipsychotics (FGAs), with most finding better
      efficacy and tolerability for SGAs. However, these 'efficacy trials' were
      generally short term and included only highly selected patients. Mostly because
      of weight gain and other metabolic effects of the SGAs, as well as their high
      acquisition price, the debate on the (cost) effectiveness of the SGAs led to two
      pragmatic clinical trials with no sponsorship by industry. Both trials had broad
      inclusion criteria and long follow-up, and tried to mimic clinical routine: CATIE
      (Clinical Antipsychotic Trials of Intervention Effectiveness) and CUtLASS (Cost
      Utility of the Latest Antipsychotic drugs in Schizophrenia Study). 1493 patients
      participated in CATIE, an 18-month, double-blind trial comparing the SGAs
      olanzapine, quetiapine, risperidone and ziprasidone with the FGA perphenazine. If
      efficacy or tolerability was insufficient, patients were re-randomized to a
      medication other than the one they previously received. Improvement of
      psychopathology and of quality of life was only moderate. Overall, 74% of
      patients discontinued study medication before 18 months, and the median time to
      discontinuation was 4.6 months. Aside from olanzapine (time to discontinuation
      9.2 months), the other SGAs did not differ from each other or from perphenazine.
      Except for adverse effects as a reason for discontinuation, differences between
      the SGAs and the FGA were minimal. In CUtLASS, a 12-month open-label trial, 277
      patients were randomized to receive an FGA or a SGA. Again, efficacy was rather
      similar between the two groups, with only limited improvement of psychopathology
      and quality of life. The authors of both trials concluded that SGAs do not
      markedly differ from FGAs regarding compliance, quality of life and
      effectiveness. The methodological problems of both trials have been discussed
      extensively. Patients had psychotic symptoms that were moderate in severity and
      were at least partially treatment resistant. The marginal improvement observed
      indicated that this population might not be appropriate to detect differences
      between FGAs and SGAs. Specific issues of CATIE include the exclusion of patients
      with tardive dyskinesia in the perphenazine arm and the high discontinuation
      rate. In CUtLASS, the concept of including 13 different FGAs and four SGAs in the
      respective classes was problematic. It is of interest that the most widely
      prescribed drug was sulpiride--of the FGAs, this is probably the 'most atypical'
      drug. Aside from the finding that the advantages of the SGAs are not as strong as
      early trials and marketing suggested or promised, the trials do not provide much
      helpful information regarding everyday practice. For tardive dyskinesia, no
      conclusions at all can be drawn. Similarly, methodological problems inhibited the
      detection of the other major advantage of the SGAs, i.e. the improved subjective
      well-being/quality of life while receiving these agents. It is well known that
      patients' and doctors' perspectives differ markedly, and the Quality of Life
      Scale (QLS), an expert-rated scale used in both trials, might not be sensitive
      enough to detect the subjective advantages reported by the majority of patients
      in other trials. CATIE and CUtLASS suggest that SGAs do not live up to all the
      previous expectations. However, even if most of these advantages are debatable,
      the lower risk of tardive dyskinesia and the better subjective effects should be
      strong enough reasons to favour these drugs. There is no single antipsychotic
      that is best for every schizophrenia patient, as individual responses differ
      markedly. For successfully individualized treatment, a multitude of antipsychotic
      options are needed.

PMID- 19594193
TI  - STAR*D: revising conventional wisdom.
AB  - The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a
      series of sequenced, randomized treatment trials following a first and, if
      needed, subsequent treatment steps to define the tolerability and effectiveness
      of various options in both acute and longer term treatment. Adult outpatients
      (n=4041) with nonpsychotic major depressive disorder, substantial chronic and
      recurrent depression, and co-morbid psychiatric and general medical conditions
      were enrolled in 41 representative primary and specialty care settings. About one
      third of participants remitted in first step treatment with citalopram, 50% of
      these within 6 weeks. Poorer outcomes were associated with minority status,
      socioeconomic disadvantage, more axis I and III co-morbid disorders, lower
      function and quality of life, and anxious and melancholic features. In step 2
      medication switch, there were no significant differences in remission among
      within-class, out-of-class or dual-action agents: sertraline (27%), bupropion
      sustained release (26%) and venlafaxine-extended release (25%). In step 2
      medication augmentation of citalopram, there was no significant difference in
      remission between bupropion-sustained release (39%) and buspirone (33%), although
      participants using bupropion-sustained release had greater symptom reduction and
      better tolerability. There were no significant differences in remission in step 2
      between cognitive therapy and medication treatment in either the switch (31% vs
      27%) or augmentation (31% vs 33%) strategies, although participants in cognitive
      therapy augmentation had a longer time to remission than those in medication
      augmentation (55 vs 40 days). In step 3, there were no differences in remission
      between a switch to mirtazapine (8%) or nortriptyline (12%), or between
      augmentation with lithium (13%) or T(3) (triiodothyronine, liothyronine) [25%],
      although more participants discontinued lithium due to adverse effects than
      discontinued T(3). In the fourth step, there was no difference in remission
      between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine
      (16%), although the combination treatment had fewer adverse effects and had the
      advantages of not requiring a washout period or diet restrictions. Participants
      requiring more than two well delivered treatments may be characterized as
      treatment resistant given the substantially lower remission rates after that
      point. Treatment resistance was associated with more concurrent axis I or III co
      morbid conditions, socioeconomic disadvantage, chronicity and melancholic or
      anxious features. However, if participants remained in treatment for up to four
      steps, about 67% reached remission. Times to remission were not substantially
      longer for later treatment steps. The importance of reaching remission is
      highlighted by the lower relapse rates in naturalistic follow-up for participants
      entering in remission compared with those entering with response but not
      remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4:
      50% vs 83%). Clinical decision making based on the itemized measurement of
      symptoms and adverse effects at each treatment visit was feasible in STAR*D's
      real world settings and resulted in adequate dosages and durations of treatment
      that generally exceeded those typically found in practice settings. Although
      switch and augmentation strategies could not be directly compared due to the
      equipoise stratified randomized design, the higher remission rates at step 2 with
      medication augmentation are intriguing and merit further study.

PMID- 19594195
TI  - Tobacco smoking in individuals with attention-deficit hyperactivity disorder:
      epidemiology and pharmacological approaches to cessation.
AB  - The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and nicotine
      dependence is common. Individuals with ADHD are more likely to initiate smoking
      and become dependent on nicotine than their non-ADHD counterparts, and recent
      evidence suggests that they may have more difficulty quitting smoking. Little is
      known about how to best approach treating these co-morbidities to optimize
      clinical outcome. Clinicians treating individuals with either ADHD or nicotine
      dependence should be aware of their common co-occurrence and the need to address
      both in treatment. This review of ADHD and nicotine dependence provides an
      overview of relevant epidemiology, bidirectional interactions and implications
      for pharmacological and adjunctive psychosocial treatment. Incorporating the
      current evidence base and their clinical experience, the authors propose a
      stepwise approach to treating patients with co-morbid ADHD and nicotine
      dependence. Given the potential for ADHD symptoms to interfere with smoking
      cessation success, the first priority is to stabilize ADHD. The first-line
      pharmacological approach should be a long-acting psychostimulant. Upon ADHD
      stabilization, motivational techniques should be used to encourage readiness for
      a smoking cessation attempt. In the context of behavioural cessation
      interventions sensitive to the patient's needs and developmental stage,
      pharmacological intervention targeting smoking cessation may be initiated. The
      authors recommend varenicline as a first-line agent, given its superior effect
      size among available medication treatments. Symptoms of ADHD, as well as nicotine
      withdrawal and craving symptoms, should be monitored closely during the cessation
      attempt, and adjustments to therapy should be considered if warranted. The
      authors conclude that, while current treatments may potentially be effective for
      co-morbid ADHD and nicotine dependence, further research is needed to parse the
      complex associations between these disorders and prospectively study combined
      treatments.

PMID- 19594196
TI  - The management of breakthrough pain during labour.
AB  - There is a long history of attempts to alleviate the pain of childbirth,
      particularly in Asian and Middle Eastern civilisations. In the UK, it was the
      administration of chloroform to Queen Victoria by John Snow in 1853 that is
      widely credited with popularizing the idea that labour pain should and could be
      treated. Medical analgesia is now well established around the globe with a wealth
      of research evidence describing methods, efficacy and complications. In this
      article, we define 'primary breakthrough pain' as the moment when a woman first
      requests analgesia during labour. The management of this can include simple
      emotional support, inhaled analgesics, parenteral opioids and epidural analgesia.
      'Secondary breakthrough pain' can be defined as the moment when previously used
      analgesia becomes ineffective. We concentrate our discussion of this phenomenon
      on the situation when epidural analgesia begins to fail. Only epidural analgesia
      offers the potential for complete analgesia, so when this effect is lost the
      recipient can experience significant distress and dissatisfaction. The best
      strategy to avert this problem is prevention by using the best techniques for
      epidural catheterisation and the most effective drug combinations. Even then,
      epidurals can lose their efficacy for a variety of reasons, and management is
      hampered by the fact that each rescue manoeuvre takes about 30 minutes to be
      effective. If the rescue protocol is too cautious, analgesia may not be
      successfully restored before delivery, leading to patient dissatisfaction. We
      therefore propose an aggressive response to epidural breakthrough pain using
      appropriate drug supplementation and, if necessary, the placement of a new
      epidural catheter. Combined spinal epidural techniques offer several advantages
      in this situation. The goal is to re-establish analgesia within 1 hour. The
      primary aim of pain management during labour and delivery is to provide the level
      of comfort determined as acceptable to each individual woman. Some require little
      or no analgesia, while others demand complete abolition of pain. Whatever the
      individual's personal point of breakthrough pain is, supporting clinicians should
      respond logically and rapidly to re-establish analgesia using locally agreed
      protocols. This approach will maximize patient satisfaction and hopefully
      increase the pleasure and satisfaction of childbirth.

PMID- 19594198
TI  - Patients' attitudes towards generic substitution of oral atypical antipsychotics:
      a questionnaire-based survey in a hypothetical pharmacy setting.
AB  - BACKGROUND: Generic atypical antipsychotics in tablet form differ in name,
      appearance and packaging from the innovator brand antipsychotics. These
      differences might cause anxiety, confusion and misperceptions in some ambulant
      patients with psychoses/schizophrenia, especially if the brand atypical
      antipsychotic is substituted in the pharmacy without the acknowledgement of the
      patient and treating psychiatrist. Furthermore, generic substitution of branded
      oral atypical antipsychotics in the pharmacy might cause nonadherence and
      potentially lead to suboptimal treatment outcomes if patients perceive the
      medicines to be clinically different. OBJECTIVE: To determine the attitudes of
      patients with psychoses/schizophrenia towards generic substitution of oral
      atypical antipsychotics in a pharmacy setting. METHODS: A total of 106 ambulant
      patients with psychoses/schizophrenia currently taking an oral atypical
      antipsychotic (risperidone [Risperdal], olanzapine [Zyprexa], quetiapine
      [Seroquel] or aripiprazole [Abilify]) were confronted with generic substitution
      in a hypothetical pharmacy setting.Two conditions were used: one granting
      patients a short explanation about the substitution, and one without explanation.
      Patients' attitudes towards the generic substitution were assessed using a
      combined quantitative and qualitative design. RESULTS: Of the respondents, 73%
      stated that they would be unlikely to take a generic antipsychotic if their
      pharmacist were to substitute it. Providing patients with a short explanation had
      a significantly positive effect on their intention to take a generic version;
      however, overall, the patients' intention to take the generic antipsychotic lay
      well below a neutral midpoint. CONCLUSION: Patients with psychoses/schizophrenia
      using atypical antipsychotics in tablet form perceive generic versions of their
      antipsychotics as being significantly different. This perceived difference lowers
      their intention of continuing to take the medication, thus possibly jeopardizing
      treatment outcome. Caution with the generic substitution of atypical
      antipsychotics in the pharmacy is therefore recommended. Generic substitution
      should take place only with the knowledge and agreement of the psychiatrist and
      the patient.

PMID- 19594199
TI  - Zonisamide: in Parkinson's disease.
AB  - Zonisamide, a widely available antiepileptic drug, has been approved in Japan as
      adjunctive therapy with levodopa for the treatment of previously treated patients
      with Parkinson's disease. It is an oral 1,2-benzisoxazole-3-methanesulfonamide
      and is associated with increased striatal dopamine levels in animal models. In
      two 12-week, randomized, double-blind, multicentre trials in adult patients with
      inadequately controlled Parkinson's disease and receiving levodopa, zonisamide 25
      mg once daily (the recommended dosage) significantly improved motor function from
      baseline at final assessment, as assessed by the Unified Parkinson's Disease
      Rating Scale (UPDRS) Part III total score (primary endpoint), compared with
      placebo. Zonisamide 25 mg once daily as adjunctive therapy with levodopa was
      generally well tolerated by patients with Parkinson's disease. The overall
      incidence of adverse events was not significantly different between zonisamide 25
      mg once daily and placebo groups in the phase IIb/III trial.

PMID- 19594200
TI  - Embolism of brain tissue in intrapartum and early neonatal deaths: report of 9
      cases.
AB  - We report the clinical features and pathological findings in 9 cases of
      intrapartum and early neonatal death associated with embolism of brain tissue to
      the pulmonary and systemic circulation following difficult delivery. All except 1
      of the cases in this series were born at, or near to, term, were vertex
      presentations, and were normally grown. All followed instrumental delivery and in
      5, at least one mode of assisted delivery had failed. Whilst some evidence of
      cranial trauma was present in 7 cases, only 3 had skull fractures and 7 showed
      intracranial hemorrhage, although this was described as minor in 3. Emboli of
      brain tissue were identified in the pulmonary circulation in all cases. Fragments
      of brain were also seen in vessels of other organs, in particular the heart, in 6
      cases. Emboli were highlighted by immunostaining for glial fibrillary acid
      protein. Brain emboli should be sought in all post mortems of unexplained
      intrapartum or early neonatal death following difficult delivery, even in the
      absence of overt cranial trauma. Disseminated intravascular coagulation is a
      frequent association. Extensive sampling for histology, particularly of the lungs
      and coronary vessels, is essential if this condition is not to be missed.

PMID- 19594201
TI  - The use of comparative genomic hybridization and fluorescent in situ
      hybridization in postmortem pathology investigation of congenital malformations.
AB  - Chromosomal abnormalities are an important cause of multiple congenital anomalies
      (MCA). However, conventional cytogenetic analysis using culture is unsuccessful
      in 10% to 40% of the cases. The purpose of this study was to examine if
      retrospective chromosomal analysis was possible on paraffin-embedded autopsy
      material with new techniques, including comparative genomic hybridization (CGH)
      and fluorescent in situ hybridization (FISH). We investigated 92 patients,
      including 71 patients with MCA, 17 patients with an isolated congenital anomaly,
      and 4 normal controls, by conventional CGH analysis and/or FISH. The karyotype
      was known in 52 cases, of which 26 patients were normal and 26 had chromosomal
      anomalies. Comparative genomic hybridization or FISH confirmed all but 2 cases,
      which were not interpretable. In 40 patients the karyotype was unknown but could
      be analyzed successfully in 36 cases (90%) by CGH. In this series, we found 1
      additional chromosomal aberration, 45,X (Turner syndrome). Furthermore, we
      examined the postmortem material of 12 patients by FISH, confirming a known
      abnormal karyotype in 9 patients, an abnormal karyotype found by CGH in 1 case,
      and confirming DiGeorge syndrome (22q11 deletion) in twins. Comparative genomic
      hybridization and FISH are reliable techniques with which to perform
      retrospective genetic analysis on paraffin-embedded autopsy material.

PMID- 19594197
TI  - GABA(B) receptors, schizophrenia and sleep dysfunction: a review of the
      relationship and its potential clinical and therapeutic implications.
AB  - Evidence for an intrinsic relationship between sleep, cognition and the
      symptomatic manifestations of schizophrenia is accumulating. This review presents
      evidence for the possible utility of GABA(B) receptor agonists for the treatment
      of subjective and objective sleep abnormalities related to schizophrenia. At the
      phenotypic level, sleep disturbance occurs in 16-30% of patients with
      schizophrenia and is related to reduced quality of life and poor coping skills.
      On the neurophysiological level, studies suggest that sleep deficits reflect a
      core component of schizophrenia. Specifically, slow-wave sleep deficits, which
      are inversely correlated with cognition scores, are seen. Moreover, sleep plays
      an increasingly well documented role in memory consolidation in schizophrenia.
      Correlations of slow-wave sleep deficits with impaired reaction time and
      declarative memory have also been reported. Thus, both behavioural insomnia and
      sleep architecture are critical therapeutic targets in patients with
      schizophrenia. However, long-term treatment with antipsychotics often results in
      residual sleep dysfunction and does not improve slow-wave sleep, and adjunctive
      GABA(A) receptor modulators, such as benzodiazepines and zolpidem, can impair
      sleep architecture and cognition in schizophrenia. GABA(B) receptor agonists have
      therapeutic potential in schizophrenia. These agents have minimal effect on rapid
      eye movement sleep while increasing slow-wave sleep. Preclinical associations
      with increased expression of genes related to slow-wave sleep production and
      circadian rhythm function have also been reported. GABA(B) receptor deficits
      result in a sustained hyperdopaminergic state and can be reversed by a GABA(B)
      receptor agonist. Genetic, postmortem and electrophysiological studies also
      associate GABA(B) receptors with schizophrenia. While studies thus far have not
      shown significant effects, prior focus on the use of GABA(B) receptor agonists
      has been on the positive symptoms of schizophrenia, with minimal investigation of
      GABA(B) receptor agonists such as baclofen or gamma-hydroxybutyric acid and their
      effects on sleep architecture, cognition and negative symptoms in patients with
      schizophrenia. Further study is needed.

PMID- 19594205
TI  - Polygraphy of sleep at altitudes between 5300 m and 7500 m during an expedition
      to Mt. Everest (MedEx 2006).
AB  - OBJECTIVES: Sleep at extreme altitudes is characterized by the repetitive
      occurrence of central apneas that in some cases may lead to a marked decrease in
      arterial oxygen saturation. During the Ludwig Maximilians University Expedition
      to Mt. Everest (MedEx 2006), nocturnal polygraphic recordings were made at
      different altitudes and included the first recordings ever made at 7500 m, which
      were completed on 8 separate occasions during the expedition. METHODS: The study
      was performed on the author (K.M., 58 years, 181 cm, 75 kg), who is an
      experienced high-altitude mountaineer. The standard polygraphic parameters, such
      as nasal and oral airflow, thoracic and abdominal effort, oxygen saturation,
      heart rate, body position, movement, and snoring, were collected with a portable
      sleep recording device (AlphaScreen, SensorMedics, Germany, Hochberg) at
      different altitudes between 5300 m and 7500 m, and were compared with baseline
      assessments made in Munich, Germany (altitude 508 m). The daytime value of oxygen
      saturation at rest was measured at South Col (8000 m) and at the South Summit
      (8763 m) without breathing supplemental oxygen for at least 10 minutes. RESULTS:
      The number of apneas and hypopneas of central origin increased up to a maximum of
      148/h with a minimal blood oxygen saturation of 48% at 7500 m, compared with <5/h
      at Munich. After 11 days of acclimatization, data recorded at 5300 m showed a
      marked reduction of disturbed sleep. The Apnea-Hypopnea-Index dropped from 138/h
      to 51/h, and the minimal blood oxygen saturation rose from 57% to 67%. At South
      Col (8000 m), the daytime value of oxygen saturation at rest ranged between 53%
      and 55%, and on South Summit (8673 m) without breathing supplemental oxygen for
      at least 10 minutes, it fluctuated around 50%. CONCLUSIONS: These data correlate
      well compared with those obtained in hypobaric chamber studies and show that
      regardless of physiologic adjustment to low oxygen conditions at Base Camp
      altitude, during the final summit attempt oxygen saturation drops further to 55%
      and even less. Thus recordings of nocturnal oxygen saturation at Camp 3 (7500 m)
      on Everest, where the night is spent before the summit attempt, may help to show
      the actual efficiency of hypoxic ventilatory response and to detect the
      individual hypoxic tolerance to altitudes above 8000 m.

PMID- 19594203
TI  - Scorpion sting envenomation in children in southeast Turkey.
AB  - BACKGROUND: Scorpion sting envenomation is a life-threatening emergency and a
      common public health problem in many regions of the world, particularly in
      children. Children are at greater risk of developing severe cardiac, respiratory,
      and neurological complications. OBJECTIVES: The aims of this study were to
      evaluate demographic, clinical, laboratory, treatment, and outcome
      characteristics for pediatric patients with scorpion sting envenomation in
      southeast Turkey and to describe features that may be predictive of the need for
      pediatric intensive care unit (PICU) care. METHODS: A total of 52 charts of
      children (mean age: 7.7 +/- 2.8 years; age range: 1.5-15 years) presenting with
      scorpion sting envenomation to a single hospital in southeastern Turkey were
      investigated. General characteristics of the children, species of the scorpions,
      anatomic site of the sting, clinical and laboratory findings, treatment
      approaches, complications, and outcomes were recorded. RESULTS: Twenty-four
      stings (46.2%) were inflicted by Androctonus crassicauda, 1 (1.9%) by Leiurus
      quinquestriatus, and the sources of the other stings were not known. Thirty-one
      patients (59.6%) were admitted from rural areas. Admission from a rural area was
      a significant risk factor for severe envenomation. Foot-leg was the most
      frequently stung part of the body (48%). The greatest number of stings occurred
      in the summer (78.8%). Cold extremities and tachycardia were the most frequently
      seen clinical findings (38.4% for both). Twenty patients (38.5%) had signs of
      serious envenomation and required admission to the PICU. Hemoglobin, white blood
      cell count, activated prothrombin time, aspartate aminotransferase, alanine
      aminotransferase, and creatine phosphokinase levels were higher in severely
      envenomed children compared to levels in those with mild-moderate stings.
      Antivenom was given at a primary or secondary health center before arrival to our
      hospital in 44 (84.6%) patients, without any apparent difference in the number of
      patients presenting with mild-moderate and severe envenomed stings. All patients
      recovered after treatment except for 1 child who died with severe pulmonary
      edema. CONCLUSIONS: We found no clinically useful demographic or epidemiological
      data to guide decision making regarding the need for PICU admission for pediatric
      victims of scorpion sting in our area. Decisions on transfer and admission to a
      PICU should be based on the development of systemic findings of envenomation.

PMID- 19594206
TI  - Comparison of a SAM splint-molded cervical collar with a Philadelphia cervical
      collar.
AB  - OBJECTIVE: To compare the effectiveness of a SAM splint molded into a cervical
      collar with that of a Philadelphia cervical collar at limiting movement of the
      cervical spine in 5 different movements. METHODS: This study was prospectively
      carried out in 13 healthy volunteer subjects. A hand-held goniometer was then
      used to measure degrees of maximal extension (starting in a maximally flexed
      position), rotation (left and right), and lateral flexion (left and right) with
      each collar. The results were then analyzed for the 5 independent movements using
      the paired t test to determine the effectiveness of the SAM splint compared with
      that of the Philadelphia collar. RESULTS: There was no statistically significant
      difference between the Philadelphia collar and the SAM splint at limiting
      movement of the cervical spine in any of the measured movements or in total
      allowed degrees of movement. CONCLUSION: The results of this study suggest that
      the SAM splint, when molded into a cervical collar, is as effective as the
      Philadelphia collar at limiting movement of the cervical spine.

PMID- 19594207
TI  - Exercise-associated hyponatremia: overzealous fluid consumption.
AB  - Exercise-associated hyponatremia is hyponatremia occurring during or up to 24
      hours after prolonged exertion. In its more severe form, it manifests as cerebral
      and pulmonary edema. There have now been multiple reports of its occurring in a
      wilderness setting. It can now be considered the most important medical problem
      of endurance exercise. The Second International Exercise-Associated Hyponatremia
      Consensus Conference gives an up-to-date account of the nature and management of
      this disease. This article reviews key information from this conference and its
      statement. There is clear evidence that the primary cause of exercise-associated
      hyponatremia is fluid consumption in excess of that required to replace
      insensible losses. This is usually further complicated by the presence of
      inappropriate arginine vasopressin secretion, which decreases the ability to
      renally excrete the excess fluid consumed. Women, those of low body weight, and
      those taking nonsteroidal anti-inflammatory drugs are particularly at risk. When
      able to be biochemically diagnosed, severe exercise-associated hyponatremia is
      treated with hypertonic saline. In a wilderness setting, the key preventative
      intervention is moderate fluid consumption based on perceived need ("ad libitum")
      and not on a rigid rule. (Editor's Note: This paper was written at my request in
      an effort to increase awareness of this important clinical entity among members
      of the wilderness community, many of whom are involved in activities that place
      them at risk of its development. I thank the authors for their diligent efforts.)

PMID- 19594208
TI  - Antisnake venom production crisis--who told us it was uneconomic and
      unsustainable?
AB  - The world of antisnake venom production is currently a gloomy place to visit. It
      is described as being in crisis, characterized by shortages, producers leaving
      the market, high prices, and unsustainability. It has been reduced to a pauper
      like status, doomed to relying on charitable handouts for resolution. The
      worrying aspect of this is that little work has been done to establish the true
      economics and return on antisnake venom if provided by private companies.
      Fortunately, it is amenable to economic analysis, and in this manner, a rational
      approach to further development and distribution can be obtained. This article
      proposes a model antisnake venom (ASV) production unit and shows the likely
      economics and return based on the production of various volumes of ASV. It
      estimates the costs for the key components of the unit, which are production
      equipment and staffing. A profit and loss account and balance sheet are
      constructed for the unit, and the effects of ASV volume and neutralizing titres
      are demonstrated. It is our contention that ASV production can be sustained at
      affordable prices in the developing world. We recommend that any solution to the
      ASV shortage must take into account the most cost efficient method(s) of
      production.

PMID- 19594209
TI  - Recombinant factor VIIa for treatment of gastrointestinal hemorrhage following
      rattlesnake envenomation.
AB  - North American rattlesnakes possess venom with primarily cytotoxic and hemotoxic
      properties. When persons are envenomated by these snakes, thrombocytopenia and
      coagulopathy commonly occur, yet patients rarely develop severe bleeding. This
      report describes a 44-year-old Native American man bitten on the index finger by
      an unknown species of rattlesnake. The man developed massive gastrointestinal
      hemorrhage that was ultimately treated with recombinant factor VIIa. He presented
      to an emergency department with a depressed level of consciousness, a blood
      pressure of 60/20 mm Hg, and heart rate of 148 beats per minute. He was
      diaphoretic and vomiting bright red blood. Initial laboratory results revealed
      thrombocytopenia and coagulopathy. Despite aggressive fluid resuscitation and
      administration of blood and antivenom in the emergency department, the patient
      continued to have profuse upper gastrointestinal bleeding, with hemoglobin as low
      as 1.8 g/dL. He received fluids, antivenom, and multiple blood products, with
      cessation of bleeding after administration of recombinant factor VIIa.
      Esophagogastroduodenoscopy revealed a single Mallory-Weiss tear as the source of
      hemorrhage. The patient stabilized after 6 hours of aggressive resuscitation but
      over the next several days developed several complications, including acute renal
      failure and gram-negative sepsis. The patient died on hospital day 5. In cases of
      life-threatening hemorrhage after rattlesnake envenomation in which traditional
      therapy with antivenom and aggressive supportive measures fail, recombinant
      factor VIIa should be considered as an additional therapeutic option to achieve
      hemostasis.

PMID- 19594210
TI  - Wilderness first aid: managing remote area medical issues.

PMID- 19594211
TI  - A prospective, multi-year analysis of illness and injury during summer travel to
      arid environments.
AB  - OBJECTIVE: There exist no prospectively generated analyses of the type and
      frequency of medical incidents in desert settings. We created a database of every
      illness and injury during 6 field seasons in the Gobi Desert in order to optimize
      expedition medical and safety planning. METHODS: Every incident presenting to the
      expeditions' physicians, regardless of type, magnitude, treatment, or outcome,
      was recorded. Incidents ranged from headache, insomnia, and diarrhea to
      lacerations, infection, fights, psychosis, and foreign body extraction and were
      thus categorized, segregating urban travel-related complaints from illness and
      injury occurring in the desert setting. The chronology of incidents and illnesses
      was observed. The incidence of categorized illness and injury was analyzed using
      descriptive statistics and was presented in terms of person-days in the field.
      RESULTS: There were 412 incidents recorded during 2689 person-days from 6 field
      seasons in the Gobi Desert from 2003 through 2007. The expeditions' physicians
      saw an average of 2.2 incidents x d(-1) in the urban setting compared to 3.6
      incidents x d(-1) in the desert. Circadian rhythm disturbances, gastrointestinal
      illnesses, and musculoskeletal complaints predominated in the urban setting,
      while minor trauma, heat-related exposures, and gastrointestinal and orthopedic
      problems predominated in the desert setting. Our data show an absolute risk of
      illness or injury of 153.2 incidents per 1000 person-days and a risk of
      "gastrointestinal" and "trauma" complaints of 21.2 and 23.1 per 1000 person-days,
      respectively. CONCLUSIONS: Herein we describe results from the first ever
      prospective study of the hazards of travel in an arid environment. We observed
      that there are patterns of injury and illness that are consistent across
      expeditions to the Gobi Desert. For example, while heat- and wind-exposure
      related illness and injury in the desert are quite common, other aspects of the
      desert environment are very forgiving. Perhaps the most interesting finding in
      our cohort was the degree to which different problems occurred at different
      stages of the expeditions. Our data sets suggest several future studies to
      evaluate patterns of illness and injury and could be an asset to recreational
      travelers and religious pilgrims, as well as to those sending employees to
      extreme environments.

PMID- 19594212
TI  - Prevalence of airway obstruction in recreational SCUBA divers.
AB  - OBJECTIVE: The prevalence of airflow obstruction in recreational self-contained
      underwater breathing apparatus (SCUBA) divers is unknown. Since airflow
      obstruction is a relative contraindication for diving, we conducted a study to
      determine its prevalence and magnitude in a cohort of recreational divers in
      Saba, Netherlands Antilles. METHODS: Prior to diving, divers were asked to
      complete a diving/health questionnaire and then to perform spirometry
      administered by trained dive store personnel. Spirometry instrumentation provided
      immediate feedback regarding test quality. RESULTS: Of 8365 eligible divers
      during the study period (November 1997-March 1999), 668 enrolled and completed
      questionnaires. Of those completing questionnaires, 46% reported a history of
      smoking, 13% were current smokers, 15% wheezed, 6% had asthma, 4% used
      bronchodilators, and 3% took oral steroids. Of 654 completing spirometry, 231 had
      acceptable spirometry quality and complete questionnaires. By forced expiratory
      volume in 1 second/forced vital capacity, 10% had mild, 1.7% had moderate, and
      0.4% had severe airflow obstruction. CONCLUSIONS: The prevalence of airflow
      obstruction was 6% to 15% by report and 12% by spirometry, approximating the
      combined prevalence of asthma and chronic obstructive pulmonary disease in the
      general population. Study limitations include possible self-selection and low
      enrollment rate. Prospective lung function testing can be conducted at remote
      sites using nonmedical personnel as "testers." This study could guide future
      investigations to determine if asthma is a risk factor for decompression illness.

PMID- 19594213
TI  - Wilderness first aid: is there an "industry standard"?
AB  - OBJECTIVE: To determine if an "industry standard" exists for wilderness first aid
      training and certification of outdoor adventure/education leaders. METHODS:
      Regulatory authorities, national organizations, and school/college groups were
      queried with regard to their requirements for first aid training of their
      wilderness trek leaders. RESULTS: Only 10 of the 22 states with guide licensure
      programs required any first aid training as a condition of licensure, and none
      specified a specific course. Of those programs requiring such training, the
      requirements ranged from a 6-hour standard first aid course to more structured
      "wilderness first responder" certification. CONCLUSIONS: There exists no uniform
      industry standard for first aid training and certification of wilderness leaders.
      The epidemiology of backcountry injuries as well as what is currently known about
      clinical skills retention indicate that there may be little evidence basis for
      much of current practice.

PMID- 19594214
TI  - Can people with Raynaud's phenomenon travel to high altitude?
AB  - OBJECTIVE: To determine whether high altitude travel adversely affects mountain
      enthusiasts with Raynaud's phenomenon. METHODS: Volunteers with Raynaud's
      phenomenon were recruited using announcements disseminated by organizations
      dedicated to climbing or wilderness travel and Internet discussion boards
      dedicated to mountain activities to complete an online, anonymous survey. Survey
      questions addressed demographic variables, aspects of their Raynaud's phenomenon,
      and features of their mountain activities. Respondents compared experiences with
      Raynaud's phenomenon between high (>2440 m; 8000 feet) and low elevations and
      rated agreement with statements concerning their disease and the effects of high
      altitude. RESULTS: One hundred forty-two people, 98% of whom had primary
      Raynaud's phenomenon, completed the questionnaire. Respondents spent 5 to 7 days
      per month at elevations above 2440 m and engaged in 5.4 +/- 2.0 different
      activities. Eighty-nine percent of respondents engaged in winter sports and only
      22% reported changing their mountain activities because of Raynaud's phenomenon.
      Respondents reported a variety of tactics to prevent and treat Raynaud's attacks,
      but only 12% used prophylactic medications. Fifteen percent of respondents
      reported an episode of frostbite following a Raynaud's phenomenon attack at high
      altitude. There was considerable heterogeneity in participants' perceptions of
      the frequency, duration, and severity of attacks at high altitude compared to
      their home elevation. CONCLUSIONS: Motivated individuals with primary Raynaud's
      phenomenon, employing various prevention and treatment strategies, can engage in
      different activities, including winter sports, at altitudes above 2440 m.
      Frostbite may be common in this population at high altitude, and care must be
      taken to prevent its occurrence.

PMID- 19594219
TI  - The problem with the double-edged solution.

PMID- 19594215
TI  - Eye problems in mountain and remote areas: prevention and onsite treatment-
      official recommendations of the International Commission for Mountain Emergency
      Medicine ICAR MEDCOM.
AB  - Although eyes are not frequently injured in the mountains, they are exposed to
      many adverse factors from the environment. This article, intended for first
      responders, paramedics, physicians, and mountaineers, is the consensus opinion of
      the International Commission for Mountain Emergency Medicine (ICAR-MEDCOM). Its
      aim is to give practical advice on the management of eye problems in mountainous
      and remote areas. Snow blindness and minor injuries, such as conjunctival and
      corneal foreign bodies, could immobilize a person and put him or her at risk of
      other injuries. Blunt or penetrating trauma can result in the loss of sight in
      the eye; this may be preventable if the injury is managed properly. In almost all
      cases of severe eye trauma, protecting the eye and arranging an immediate
      evacuation are necessary. The most common eye problems, however, are due to
      ultraviolet light and high altitude. People wearing contact lenses and with
      previous history of eye diseases are more vulnerable. Any sight-threatening eye
      problem or unexplained visual loss at high altitude necessitates descent. Wearing
      appropriate eye protection, such as sunglasses with sidepieces and goggles with
      polarized or photochromic lenses, could prevent most of the common eye problems
      in mountaineering.

PMID- 19594220
TI  - Study suggests antioxidants inhibit exercise-induced insulin sensitivity.

PMID- 19594221
TI  - The benefit of pre- and post-challenge urine heavy metal testing: part 2.
AB  - Measuring heavy metal levels in the urine is an accepted method for assessing the
      presence of a heavy metal burden in an individual. Random samples (without a
      flushing agent) are excellent for showing current exposures, as they reflect the
      level of heavy metals in the bloodstream during the hours immediately before
      bladder voiding. Samples taken after using a heavy metal mobilizing agent are a
      reflection of total body burden. Part 1 reviewed the benefits of doing pre-flush
      (baseline) testing utilizing the published Centers for Disease Control (CDC)
      heavy metal normal ranges for interpretation that allow the clinician to identify
      current exposures to lead and mercury and to identify cadmium toxicity. In part 2
      the benefits of doing both pre- and post-challenge testing are reviewed.
      Information gleaned from performing both tests is unparalleled in allowing the
      clinician to identify which chelating agent will be most effective for the
      patient. If oral agents are employed, then possible absorption problems can be
      identified. Since none of these benefits are realized with only post-flush
      testing, it is recommended that clinicians do heavy metal testing both before and
      after a challenge with an effective and proven heavy metal mobilizing agent. The
      pitfalls of oral chelation in the case of malabsorption syndromes, such as gluten
      intolerance, are also discussed.

PMID- 19594222
TI  - Nutrients and botanicals for treatment of stress: adrenal fatigue,
      neurotransmitter imbalance, anxiety, and restless sleep.
AB  - Research shows a dramatic increase in use of the medical system during times of
      stress, such as job insecurity. Stress is a factor in many illnesses - from
      headaches to heart disease, and immune deficiencies to digestive problems. A
      substantial contributor to stress-induced decline in health appears to be an
      increased production of stress hormones and subsequent decreased immune function.
      Non-pharmaceutical approaches have much to offer such patients. This article
      focuses on the use of nutrients and botanicals to support the adrenals, balance
      neurotransmitters, treat acute anxiety, and support restful sleep.

PMID- 19594223
TI  - Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a
      review of preclinical and clinical research.
AB  - Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a
      treatment for inflammatory conditions. Turmeric constituents include the three
      curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one
      responsible for its vibrant yellow color), demethoxycurcumin, and
      bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and
      zingiberone), sugars, proteins, and resins. While numerous pharmacological
      activities, including antioxidant and antimicrobial properties, have been
      attributed to curcumin, this article focuses on curcumin's anti-inflammatory
      properties and its use for inflammatory conditions. Curcumin's effect on cancer
      (from an anti-inflammatory perspective) will also be discussed; however, an
      exhaustive review of its many anticancer mechanisms is outside the scope of this
      article. Research has shown curcumin to be a highly pleiotropic molecule capable
      of interacting with numerous molecular targets involved in inflammation. Based on
      early cell culture and animal research, clinical trials indicate curcumin may
      have potential as a therapeutic agent in diseases such as inflammatory bowel
      disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as
      certain types of cancer. Because of curcumin's rapid plasma clearance and
      conjugation, its therapeutic usefulness has been somewhat limited, leading
      researchers to investigate the benefits of complexing curcumin with other
      substances to increase systemic bioavailability. Numerous in-progress clinical
      trials should provide an even deeper understanding of the mechanisms and
      therapeutic potential of curcumin.

PMID- 19594224
TI  - Greenselect Phytosome as an adjunct to a low-calorie diet for treatment of
      obesity: a clinical trial.
AB  - A recently developed oral formulation in the form of coated tablets (Monoselect
      Camellia) (MonCam) containing highly bioavailable green tea extract (GreenSelect
      Phytosome) was tested in obese subjects (n=100) of both genders on a hypocaloric
      diet. Fifty subjects were assigned to the green tea extract plus hypocaloric
      diet, while the other 50 subjects followed the hypocaloric diet only. After 90
      days of treatment, significant weight loss and decreased body mass index (BMI)
      were observed in the group taking the herbal extract (14-kg loss in the green tea
      group compared to a 5-kg loss in the diet-only group); waistline was reduced only
      in male subjects. Besides the effect on weight and BMI, biochemical parameters
      (LDL-, HDL-, and total cholesterol, triglycerides, growth hormone, insulin-like
      growth factor-1, insulin, and cortisol) were improved in both groups. Leptin, not
      tested in the diet-only group, was reduced in patients taking MonCam. Taking into
      consideration the high safety profile of the product and the total absence of
      adverse effects observed during and after the trial, MonCam appears to be a safe
      and effective tool for weight loss.

PMID- 19594225
TI  - Evaluation of cardioprotective activity of Ginkgo biloba and Ocimum sanctum in
      rodents.
AB  - This study investigates the cardioprotective activity of a combined treatment of
      Ginkgo biloba phytosomes (GBP) and Ocimum sanctum extract (Os) in isoproterenol
      (ISO)-induced myocardial necrosis in rats. Significant myocardial necrosis,
      depletion of the endogenous antioxidants superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione
      (GSH), and increases in the serum marker enzymes aspartate aminotransferase
      (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were
      observed in ISO-treated rats compared with normal rats. Co-administration of GBP
      (100 mg per kg) with Os at two doses (50 and 75 mg per kg) for 30 days to rats
      treated with ISO (85 mg per kg, sc) on the 29th and 30th days demonstrated a
      significant decrease in ISO-induced serum marker enzyme elevations and a
      significant attenuation of the ISO-elevated myocardial lipid peroxidation marker
      malondialdehyde (MDA). A significant restoration of ISO-depleted activities and
      levels of AST, LDH, CPK, GSH, SOD, CAT, GPx, and GR in the hearts of the
      treatment groups was observed. The combination of Os 75 mg per kg and GBP 100
      mg/kg elicited greater protection than the combination of Os 50 mg per kg and GBP
      100 mg per kg. It may be concluded that GBP-Os oral treatment to ISO-challenged
      rats demonstrates significant cardiac protection, decreases lipid peroxidation,
      and restores antioxidant activities. However, the combined treatment failed to
      enhance cardioprotective activity of either herb when used alone.

PMID- 19594226
TI  - Panax ginseng. Monograph.

PMID- 19594227
TI  - Vanadium (vanadyl sulfate). Monograph.

PMID- 19594228
TI  - Effects of selection and training on unit-level performance over time: a latent
      growth modeling approach.
AB  - Surprisingly few data exist concerning whether and how utilization of job-related
      selection and training procedures affects different aspects of unit or
      organizational performance over time. The authors used longitudinal data from a
      large fast-food organization (N = 861 units) to examine how change in use of
      selection and training relates to change in unit performance. Latent growth
      modeling analyses revealed significant variation in both the use and the change
      in use of selection and training across units. Change in selection and training
      was related to change in 2 proximal unit outcomes: customer service performance
      and retention. Change in service performance, in turn, was related to change in
      the more distal outcome of unit financial performance (i.e., profits). Selection
      and training also affected financial performance, both directly and indirectly
      (e.g., through service performance). Finally, results of a cross-lagged panel
      analysis suggested the existence of a reciprocal causal relationship between the
      utilization of the human resources practices and unit performance. However, there
      was some evidence to suggest that selection and training may be associated with
      different causal sequences, such that use of the training procedure appeared to
      lead to unit performance, whereas unit performance appeared to lead to use of the
      selection procedure.

PMID- 19594229
TI  - Changes in newcomer job satisfaction over time: examining the pattern of
      honeymoons and hangovers.
AB  - In this study, the authors contribute insight into the temporal nature of work
      attitudes, examining how job satisfaction changes across the 1st year of
      employment for a sample of organizational newcomers. The authors examined factors
      related to job change (i.e., voluntary turnover, prior job satisfaction) and
      newcomer experiences (i.e., fulfillment of commitments, extent of socialization)
      that may strengthen or weaken the job satisfaction pattern. Results of a study of
      132 newcomers with data collected at 4 unique time periods show a complex
      curvilinear pattern of job satisfaction, such that satisfaction reached a peak
      following organizational entry and decreased thereafter. However, examination of
      moderating factors revealed that individuals who reported less satisfaction with
      their prior job and those having more positive experiences on the new job, such
      as greater fulfilled commitments and a higher degree of socialization, were most
      likely to experience this pattern. Findings from this study offer important
      implications for theory and research on changes in newcomer attitudes over time
      as well as practical insight on key factors that shape the pattern of job
      attitudes as individuals enter and experience a new workplace.

PMID- 19594230
TI  - Developing leaders via experience: the role of developmental challenge, learning
      orientation, and feedback availability.
AB  - Prior research offers limited insight into the types of work experiences that
      promote leadership skill development and the ways that the person and context
      shape the developmental value of these experiences. In this article, the authors
      develop a series of hypotheses linking leadership skill development to features
      of the experience (developmental challenge), person (learning orientation), and
      context (feedback availability). Based on 225 on-the-job experiences across 60
      managers, their results demonstrate that the relationship between developmental
      challenge and leadership skill development exhibits a pattern of diminishing
      returns. However, access to feedback can offset the diminishing returns
      associated with high levels of developmental challenge.

PMID- 19594231
TI  - Are cultural characteristics associated with the relationship between self and
      others' ratings of leadership?
AB  - This study examined the relationship between self and subordinate ratings of
      leadership and the relationship between self and peer ratings of leadership for
      964 managers from 21 countries. Using multilevel modeling, the authors found that
      cultural characteristics moderated the relationship between self and others'
      ratings of leadership. Specifically, the relationship between self and
      subordinate ratings, as well as between self and peer ratings, was more positive
      in countries that are characterized by high assertiveness. The relationship
      between self and subordinate ratings, as well as between self and peer ratings,
      was also more positive in countries characterized by high power distance. The
      authors also found a leniency bias in individualistic cultures for self, peer,
      and subordinate ratings. In sum, cultural characteristics should be considered in
      attempts to understand relationships between self and other ratings.

PMID- 19594232
TI  - When does self-sacrificial leadership motivate prosocial behavior? It depends on
      followers' prevention focus.
AB  - In the present set of studies, the authors examine the idea that self-sacrificial
      leadership motivates follower prosocial behavior, particularly among followers
      with a prevention focus. Drawing on the self-sacrificial leadership literature
      and regulatory focus theory, the authors provide results from 4 studies (1
      laboratory and 3 field studies) that support the research hypothesis.
      Specifically, the relationship between self-sacrificial leadership and prosocial
      behavior (i.e., cooperation, organizational citizenship behavior) is stronger
      among followers who are high in prevention focus. Implications for the importance
      of taking a follower-centered approach to leadership are discussed.

PMID- 19594233
TI  - Good soldiers and good actors: prosocial and impression management motives as
      interactive predictors of affiliative citizenship behaviors.
AB  - Researchers have discovered inconsistent relationships between prosocial motives
      and citizenship behaviors. We draw on impression management theory to propose
      that impression management motives strengthen the association between prosocial
      motives and affiliative citizenship by encouraging employees to express
      citizenship in ways that both "do good" and "look good." We report 2 studies that
      examine the interactions of prosocial and impression management motives as
      predictors of affiliative citizenship using multisource data from 2 different
      field samples. Across the 2 studies, we find positive interactions between
      prosocial and impression management motives as predictors of affiliative
      citizenship behaviors directed toward other people (helping and courtesy) and the
      organization (initiative). Study 2 also shows that only prosocial motives predict
      voice-a challenging citizenship behavior. Our results suggest that employees who
      are both good soldiers and good actors are most likely to emerge as good citizens
      in promoting the status quo.

PMID- 19594234
TI  - Self-interest and other-orientation in organizational behavior: implications for
      job performance, prosocial behavior, and personal initiative.
AB  - In this article, the authors develop the self-concern and other-orientation as
      moderators hypothesis. The authors argue that many theories on work behavior
      assume humans to be either self-interested or to be social in nature with strong
      other-orientation but that this assumption is empirically invalid and may lead to
      overly narrow models of work behavior. The authors instead propose that self
      concern and other-orientation are independent. The authors also propose that job
      performance, prosocial behavior, and personal initiative are a function of (a)
      individual-level attributes, such as job characteristics when employees are high
      in self-concern, and (b) group-level attributes, such as justice climate when
      employees are high in other-orientation. Three studies involving 4 samples of
      employees from a variety of organizations support these propositions.
      Implications are discussed for theory on work behavior and interventions geared
      toward job enrichment and team-based working.

PMID- 19594235
TI  - Mission possible? The performance of prosocially motivated employees depends on
      manager trustworthiness.
AB  - The authors propose that in mission-driven organizations, prosocially motivated
      employees are more likely to perform effectively when trust cues enhance their
      perceptions of task significance. The authors develop and test a model linking
      prosocial motivation, trust cues, task significance, and performance across 3
      studies of fundraisers using 3 different objective performance measures. In Study
      1, perceiving managers as trustworthy strengthened the relationship between
      employees' prosocial motivation and performance, measured in terms of calls made.
      This moderated relationship was mediated by employees' perceptions of task
      significance. Study 2 replicated the interaction of manager trustworthiness and
      prosocial motivation in predicting a new measure of performance: dollars raised.
      It also revealed 3-way interactions between prosocial motivation, manager
      trustworthiness, and dispositional trust propensity, such that high trust
      propensity compensated for low manager trustworthiness to strengthen the
      association between employees' prosocial motivation and performance. Study 3
      replicated all of the previous mediation and moderation findings in predicting
      initiative taken by professional fundraisers. Implications for work motivation,
      work design, and trust in organizations are discussed.

PMID- 19594236
TI  - Personality and citizenship behavior: the mediating role of job satisfaction.
AB  - Using meta-analytic path analysis, the authors tested several structural models
      linking agreeableness and conscientiousness to organizational citizenship
      behavior (OCB). Results showed that the 2 personality traits had both direct
      effects and indirect effects-through job satisfaction-on overall OCB. Meta
      analytic moderator analyses that distinguished between individual- and
      organization-targeted citizenship behaviors (OCB-I and OCB-O) showed that
      agreeableness was more closely related with OCB-I and conscientiousness with OCB
      O. Finally, the path analyses predicting OCB-I and OCB-O offered further support
      for the general hypothesis that these 2 constructs are distinct. That is, the
      results of these analyses revealed that agreeableness had both direct and
      indirect effects on OCB-I but only indirect effects on OCB-O, and that for
      conscientiousness the pattern of direct and indirect effects was exactly opposite
      (direct and indirect effects on OCB-O but only indirect effects on OCB-I).

PMID- 19594237
TI  - Power to the people: using learner control to improve trainee reactions and
      learning in web-based instructional environments.
AB  - This experimental study investigated the mechanisms by which learner control
      influences learning in an e-learning environment. The authors hypothesized that
      learner control would enhance learning indirectly through its effect on trainee
      reactions and learner engagement (in particular, off-task attention), such that
      learners who were more satisfied with the training and devoted more cognitive
      resources toward the instructional content versus off-task thoughts would possess
      greater posttraining knowledge. The study also examined the role of individual
      differences (training motivation and goal orientation) in the prediction of these
      2 mediating variables. A sample of 274 undergraduates completed an e-learning
      program, either with or without interactive, learner control tools. Results
      suggest that both training satisfaction and off-task attention predicted
      subsequent learning. Learner control had a positive impact on training
      satisfaction but was not related to off-task attention. The individual difference
      variables had a differential impact on the mediating variables. In particular,
      performance orientation was linked to off-task attention, whereas mastery
      orientation was found to indirectly influence satisfaction via its direct effect
      on training motivation. Implications for the design and further study of e
      learning are discussed.

PMID- 19594238
TI  - The milieu of managerial work: an integrative framework linking work context to
      role requirements.
AB  - Theoretical and empirical efforts focusing on the interplay between work context
      and managerial role requirements have been conspicuously absent in the scholarly
      literature. This paucity exists despite over 60 years of research concerning the
      requirements of managerial work and with the rather universal recognition that
      work context meaningfully shapes organizational behavior. The authors developed a
      theoretical model linking different types of role requirements to different forms
      of work context. They empirically tested this framework with a nationally
      representative sample of 8,633 incumbent spanning 52 managerial occupations.
      Findings from hierarchical linear modeling analyses demonstrated that discrete
      forms of context (task, social, and physical) exert significant and predictable
      effects on managerial role requirements.

PMID- 19594239
TI  - Looking ahead in times of uncertainty: the role of anticipatory justice in an
      organizational change context.
AB  - Our study drew on past theorizing on anticipatory justice (D. L. Shapiro & B. L.
      Kirkman, 2001) and fairness heuristic theory (K. Van den Bos, E. A. Lind, & H. A.
      M. Wilke, 2001) to build and test a model of employee reactions to a smoking ban.
      The results of a longitudinal study in a hospital showed that employee levels of
      preban anticipatory justice were predicted by their global sense of their
      supervisor's fairness. The combination of anticipatory justice and global
      supervisory fairness then predicted the experienced justice of the ban 3 months
      after its implementation, with the effects of the 2 predictors dependent on
      perceptions of uncertainty and outcome favorability regarding the ban. Finally,
      experienced (interpersonal) justice predicted significant other ratings of
      employee support for the ban.

PMID- 19594240
TI  - An experience sampling study of learning, affect, and the demands control support
      model.
AB  - The demands control support model (R. A. Karasek & T. Theorell, 1990) indicates
      that job control and social support enable workers to engage in problem solving.
      In turn, problem solving is thought to influence learning and well-being (e.g.,
      anxious affect, activated pleasant affect). Two samples (N = 78, N = 106)
      provided data up to 4 times per day for up to 5 working days. The extent to which
      job control was used for problem solving was assessed by measuring the extent to
      which participants changed aspects of their work activities to solve problems.
      The extent to which social support was used to solve problems was assessed by
      measuring the extent to which participants discussed problems to solve problems.
      Learning mediated the relationship between changing aspects of work activities to
      solve problems and activated pleasant affect. Learning also mediated the
      relationship between discussing problems to solve problems and activated pleasant
      affect. The findings indicated that how individuals use control and support to
      respond to problem-solving demands is associated with organizational and
      individual phenomena, such as learning and affective well-being.

PMID- 19594241
TI  - Positive manifold limits the relevance of content-matching strategies for
      validating selection test batteries.
AB  - Inferences about the relationships between scores on selection tests and measures
      of job performance are often made on the basis of an assessment of the match
      between the content of the test and the content of the job. However, there is
      little evidence that these test-to-job comparisons have any bearing on the
      criterion-related validity of selection tests. The authors show that conclusions
      reached in analyses of cognitive tests-that content matching is largely
      irrelevant to criterion-related validity-can be generalized to most sets of
      selection tests (e.g., psychomotor and performance tests, interview ratings,
      biodata scores, knowledge tests, work sample tests) that are positively
      correlated with one another and with the criterion. When the universe of
      potential predictors shows positive manifold, almost all possible sets of test
      batteries will yield similar outcomes and show similar validities, regardless of
      whether the content of these tests matches the content of the job.

PMID- 19594242
TI  - When is straightforwardness a liability in negotiations? The role of integrative
      potential and structural power.
AB  - Negotiations present individuals with a paradox. On the one hand, individuals are
      expected via social norms and formal regulations to be honest and straightforward
      in their negotiations. On the other hand, individuals who mislead their
      negotiation counterpart are often rewarded with more favorable settlements. The
      authors investigate this paradox by examining the relationship between
      negotiators' dispositional straightforwardness and concessions made during a
      negotiation. Drawing from the dual concern model (D. G. Pruitt & J. Z. Rubin,
      1986), the authors show how dispositional straightforwardness leads individuals
      to develop a greater concern for their counterpart's interests, which in turn
      leads to greater concession making during the negotiation. The authors then show
      how this individual-level relationship is moderated by features of the
      negotiation task, namely integrative potential and power.

PMID- 19594243
TI  - Understanding why they don't see eye to eye: an examination of leader-member
      exchange (LMX) agreement.
AB  - Although it is an explicitly dyadic approach to leadership, some leader-member
      exchange (LMX) research has been characterized by relatively low levels of
      agreement between leader and member judgments of the relationship. Using a
      combination of meta-analytic methods and primary data collection, the authors
      sought to explore several theoretically and methodologically meaningful factors
      that might account for lower levels of agreement. On the basis of data from 64
      independent samples (N = 10,884 dyads), the authors found that overall agreement
      was moderate in nature (? = .37). In addition, they found that longer
      relationship tenure, affectively oriented relationship dimensions, and ad hoc
      sampling techniques showed the highest levels of agreement. Empirical results
      from 98 matched dyads revealed that the extent of LMX agreement increases as the
      length of relationship tenure and intensity of dyadic interaction increases.
      Implications for LMX theory and future empirical research are discussed.

PMID- 19594244
TI  - Neuroticism and locus of control as moderators of the relationships of
      charismatic and autocratic leadership with burnout.
AB  - This study examined the moderating role of personality traits in the relationship
      between leader behavior and burnout. In two samples, employees (N = 91; N = 190)
      filled out the Maslach Burnout Inventory-General Survey and rated their leader's
      autocratic and charismatic leader behavior and their own neuroticism and internal
      work locus of control. As expected, neuroticism and internal work locus of
      control moderated the relationship between leader behavior and burnout. Charisma
      was associated with lower burnout, particularly for individuals low on internal
      locus. The relationship between autocratic leadership and burnout was positive
      for neurotic individuals, whereas for emotionally stable individuals this
      relationship weakened. These results were consistent across two independent
      samples: one with individual employee ratings of manager's leadership styles and
      the other with aggregate ratings of manager's leadership styles among employees
      in diverse organizations. Thus, although charismatic and autocratic leader
      behavior may respectively act to hinder or enhance overload and stress, the
      relationship between these leadership styles and burnout differs for followers
      with different traits.

PMID- 19594245
TI  - Unit-level voluntary turnover rates and customer service quality: implications of
      group cohesiveness, newcomer concentration, and size.
AB  - Despite substantial growth in the service industry and emerging work on turnover
      consequences, little research examines how unit-level turnover rates affect
      essential customer-related outcomes. The authors propose an operational
      disruption framework to explain why voluntary turnover impairs customers' service
      quality perceptions. On the basis of a sample of 75 work units and data from
      5,631 employee surveys, 59,602 customer surveys, and organizational records,
      results indicate that unit-level voluntary turnover rates are negatively related
      to service quality perceptions. The authors also examine potential boundary
      conditions related to the disruption framework. Of 3 moderators studied (group
      cohesiveness, group size, and newcomer concentration), results show that
      turnover's negative effects on service quality are more pronounced in larger
      units and in those with a greater concentration of newcomers.

PMID- 19594246
TI  - Relating indices of knowledge structure coherence and accuracy to skill-based
      performance: Is there utility in using a combination of indices?
AB  - The authors examined the relative criterion-related validity of knowledge
      structure coherence and two accuracy-based indices (closeness and correlation) as
      well as the utility of using a combination of knowledge structure indices in the
      prediction of skill acquisition and transfer. Findings from an aggregation of 5
      independent samples (N = 958) whose participants underwent training on a complex
      computer simulation indicated that coherence and the accuracy-based indices
      yielded comparable zero-order predictive validities. Support for the incremental
      validity of using a combination of indices was mixed; the most, albeit small,
      gain came in pairing coherence and closeness when predicting transfer. After
      controlling for baseline skill, general mental ability, and declarative
      knowledge, only coherence explained a statistically significant amount of unique
      variance in transfer. Overall, the results suggested that the different indices
      largely overlap in their representation of knowledge organization, but that
      coherence better reflects adaptable aspects of knowledge organization important
      to skill transfer.

PMID- 19594247
TI  - How do feelings influence effort? An empirical study of entrepreneurs' affect and
      venture effort.
AB  - How do feelings influence the effort of entrepreneurs? To obtain data on this
      issue, the authors implemented experience sampling methodology in which 46
      entrepreneurs used cell phones to provide reports on their affect, future
      temporal focus, and venture effort twice daily for 24 days. Drawing on the affect
      as-information theory, the study found that entrepreneurs' negative affect
      directly predicts entrepreneurs' effort toward tasks that are required
      immediately. Results were consistent for within-day and next-day time lags.
      Extending the theory, the study found that positive affect predicts venture
      effort beyond what is immediately required and that this relationship is mediated
      by future temporal focus. The mediating effects were significant only for next
      day outcomes. Implications of findings on the nature of the affect-effort
      relationship for different time lags are discussed.

PMID- 19594248
TI  - The effects of response instructions on situational judgment test performance and
      validity in a high-stakes context.
AB  - This study fills a key gap in research on response instructions in situational
      judgment tests (SJTs). The authors examined whether the assumptions behind the
      differential effects of knowledge and behavioral tendency SJT response
      instructions hold in a large-scale high-stakes selection context (i.e., admission
      to medical college). Candidates (N = 2,184) were randomly assigned to a knowledge
      or behavioral tendency response instruction SJT, while SJT content was kept
      constant. Contrary to prior research in low-stakes settings, no meaningfully
      important differences were found between mean scores for the response instruction
      sets. Consistent with prior research, the SJT with knowledge instructions
      correlated more highly with cognitive ability than did the SJT with behavioral
      tendency instructions. Finally, no difference was found between the criterion
      related validity of the SJTs under the two response instruction sets.

PMID- 19594249
TI  - Sexual and ethnic identity development among gay-bisexual-questioning (GBQ) male
      ethnic minority adolescents.
AB  - Identity development is a critical task of adolescence and occurs across multiple
      areas of self-identification. Although research on the identity development
      process among individuals who are ethnic and sexual minorities has been conducted
      for individuals who have 1 minority status or the other, few studies have
      examined these processes in people who are both ethnic and sexual minorities. In
      this qualitative study, the authors examined the dual identity development
      processes related to ethnic and sexual identity among gay-bisexual-questioning
      (GBQ) Latino and African American male adolescents. Results indicated that the
      processes associated with the development of sexual orientation and ethnic
      identity occur concurrently. However, the actual processes involved with the
      development of each identity not only differed, but seemed to be independent of
      each other because neither process was referenced in the development of the
      other. Overall, the process of ethnic identity development involved the process
      of becoming aware of one's ethnic and cultural heritage, whereas sexual identity
      development involved finding one's own personally relevant sexual orientation
      label and connecting to that community. The implications of these findings for
      the development of interventions to assist in the healthy development of GBQ
      adolescents are discussed.

PMID- 19594250
TI  - General and gay-related racism experienced by Latino gay men.
AB  - Latino gay men report experiences of racial discrimination within and outside the
      gay community. This study focused on correlates of racism within general and gay
      contexts. Racism was assessed in a probability sample of 911 Latino gay men
      recruited from 3 U.S. cities. Factor analysis of the 10-item scale produced 2
      factors: (a) General Racism Experiences, and (b) Racism Experiences in Gay
      Contexts. The scale and each factor showed adequate reliability and validity.
      Latino gay men with darker skin, more Indian features, more time in the United
      States, and low self-esteem reported more racism in both general and gay
      contexts. The authors examine the psychometric properties of a measure that
      assesses interpersonal racism among Latinos, report correlates of racism within a
      gay context, and provide an assessment tool for understanding the role of racism
      in the lives of Latino gay men.

PMID- 19594251
TI  - Application to graduate psychology programs by undergraduate students of color:
      the impact of a research training program.
AB  - The top 86 students were selected from a pool of approximately 400 applicants to
      a summer clinical psychology research training program for undergraduate students
      of color. Forty-three of the students were randomly assigned to 1 of 2 clinical
      psychology research training programs, and 43 were randomly assigned to a control
      condition without training. The multicultural version of the training program
      emphasized the cultural context of psychology in all areas of training, whereas
      cultural context was de-emphasized in the monocultural version of the program.
      Although the cultural content of the 2 training programs was effectively
      manipulated as indicated by a fidelity check by an outside expert, there were no
      significant differences between the effects of the 2 programs on the outcomes
      measured in this study. The primary differences in this study were between
      students who did versus those who did not participate in a training program.
      Sixty-five percent of the students who completed the multicultural training
      program applied to graduate schools in psychology, compared with 47% of those who
      completed the monocultural training program, and 31% of those in the control
      group. Participation in summer research training programs also increased self
      perceptions of multicultural competence.

PMID- 19594252
TI  - Spanish-English bilingual psychotherapists: personal and professional language
      development and use.
AB  - The rapid rise of the Spanish-speaking population in the United States has
      resulted in an increased demand for Spanish language mental health services. Yet
      little is known about the training needs of practitioners who provide those
      services. This qualitative study used in-depth telephone interviews to examine
      the experiences of 13 Spanish-English bilingual therapists, both native Spanish
      speakers and heritage speakers of Spanish, in their personal and professional
      language development and use. The phenomenological analysis highlighted the
      complexities of living in 2 worlds and providing psychological services in 2
      languages. Participants reported that they often felt isolated and disconnected
      as they struggled to learn and use the 2 languages in their personal and
      professional lives. While the participants took pride in having the skills of
      speaking 2 languages and serving a community that is in need, all were aware of
      their limitations when working bilingually, as they had not received training to
      do so. Translating their own thoughts during the session, using technical
      vocabulary, and understanding the variations of Spanish were particularly
      challenging for the participants who were heritage speakers.

PMID- 19594253
TI  - Juggling multiple racial identities: malleable racial identification and
      psychological well-being.
AB  - The authors examined the link between malleable racial identification and
      psychological well-being among self-identified multiracial adults. Malleable
      racial identification refers to the tendency to identify with different racial
      identities across different social contexts. Results across three studies
      suggested that malleable racial identification was associated with lower
      psychological well-being. Study 2 found that unstable regard (i.e., fluctuating
      private regard about their multiracial background) was the mechanism through
      which malleable racial identification predicted lower psychological health.
      Results of Study 3 suggested that dialectical self-views played an important
      moderating role that determines whether malleability is associated with negative
      psychological outcomes. The present studies uniquely show that malleable racial
      identification among multiracial people is maladaptive for psychological health,
      but that this may depend on whether or not people have tolerance for ambiguity
      and inconsistency in the self.

PMID- 19594254
TI  - Violated expectations and acculturative stress among U.S. Hispanic immigrants.
AB  - Expectancy violation theory (EVT) was tested with 112 Hispanic immigrants living
      in the United States by determining whether discrepancies between their
      retrospectively recalled pre-migration expectations about life in the United
      States and their post-migration (actual) experiences in the United States would
      predict their levels of acculturative stress. Discrepancies were assessed in 4
      domains (ability to communicate with English speakers, perceiving their
      communities and the United States as safe, obtaining adequate employment, and
      experiencing racism). Overall, the results indicated that discrepancies between
      pre-migration expectations and post-migration experiences were associated
      significantly with acculturative stress, although some of the findings were
      counter to EVT. Also, on the basis of a hierarchical regression analysis, the
      discrepancies significantly, albeit modestly, contributed to the prediction of
      acculturative stress beyond the predictive ability of general demographic
      variables and post-migration experiences. Implications for clinical interventions
      and research opportunities with EVT and Hispanic immigrants are discussed.

PMID- 19594255
TI  - Gender, family, and community correlates of mental health in South Asian
      Americans.
AB  - Nationally representative data from the National Latino and Asian American Study
      (Alegria et al., 2004) was used to examine both disorder prevalence rates and
      correlates of distress for the South Asian American subgroup (n = 164). South
      Asian Americans generally appeared to have lower or comparable rates of lifetime
      and 12-month mood and anxiety disorders when compared with the overall Asian
      American sample. A multiple-regression model fitted to predict recent
      psychological distress, with 12-month diagnosis as a covariate, found gender
      differences. For women, lack of extended family support was related to higher
      levels of distress, whereas for men, greater conflict with family culture, and a
      lower community social position (but higher U.S. social position) predicted
      higher distress scores. Findings suggest that mental health services consider a
      broad framework of psychological functioning for South Asian Americans that
      reflect their gendered, familial, and sociopolitical realities.

PMID- 19594257
TI  - Simultaneously salient Chinese and American identities: an experience sampling
      study of self-complexity, context, and positive mood among Chinese young adults.
AB  - Experience sampling data were collected from Chinese college students randomly
      prompted 6 times a day for 1 week to respond to questions about their American
      and Chinese identities, context, and mood. Applying a self-complexity framework
      to examine the psychological relevance of more than 1 identity, the author
      compared context and mood in situations in which American and Chinese identities
      were simultaneously salient with situations in which they were not. Being with
      family was associated with an increased likelihood of having simultaneously
      salient American and Chinese identities. However, across contexts, participants
      reporting a strong stable American identity were more likely to report
      simultaneously salient American and Chinese identities. Finally, simultaneously
      salient American and Chinese identities were associated with more positive mood,
      and this association was stronger for students reporting a strong stable Chinese
      identity but weaker for students reporting a strong stable American identity.

PMID- 19594258
TI  - Testing a multiple mediation model of Asian American college students'
      willingness to see a counselor.
AB  - Adapting the theory of reasoned action, the present study examined help-seeking
      beliefs, attitudes, and intent among Asian American college students (N = 110). A
      multiple mediation model was tested to see if the relation between Asian values
      and willingness to see a counselor was mediated by attitudes toward seeking
      professional psychological help and subjective norm. A bootstrapping procedure
      was used to test the multiple mediation model. Results indicated that subjective
      norm was the sole significant mediator of the effect of Asian values on
      willingness to see a counselor. The findings highlight the importance of social
      influences on help-seeking intent among Asian American college students.

PMID- 19594256
TI  - Abuse, mastery, and health among lesbian, bisexual, and two-spirit American
      Indian and Alaska Native women.
AB  - American Indian and Alaska Native (AIAN) women have endured a history of colonial
      oppression in the United States. Current manifestations of colonization include
      an epidemic of violence toward AIAN women, who often are sexually and physically
      abused from early on in life. Such violence may erode AIAN women's sense of
      agency or mastery and contribute to their poor physical and mental health
      outcomes. AIAN women who identify as lesbian, bisexual, or "two-spirit" appear to
      experience disproportionate levels of violence and may be particularly vulnerable
      to disparities in health outcomes. In this study, 152 sexual minority AIAN women
      were interviewed as part of an investigation addressing the health concerns of
      two-spirit persons. Participants reported disturbingly high prevalence of both
      sexual (85%) and physical (78%) assault, both of which were associated with worse
      overall mental and physical health. These relationships generally were mediated
      by a diminished sense of control or mastery. The need to indigenize the concept
      of mastery is discussed, as is the urgency of interventions to work toward
      decreasing levels of abuse and increasing mastery among sexual minority AIAN
      women.

PMID- 19594259
TI  - Multiculturalism and subjective happiness as mediated by cultural and relational
      variables.
AB  - A diverse ethnic context and an increasing immigrant youth population will soon
      become the reality across the entire U.S. demographic landscape. Research has
      suggested that a multicultural context positively influences ethnic minority and
      immigrant youth by fostering ethnic identity and psychosocial development.
      However, it is unknown whether and how perceived multiculturalism can affect
      positive youth outcomes such as life satisfaction and subjective happiness. This
      study explored perceived school multiculturalism among 338 ethnic minority and
      immigrant youth, and found a positive relation between perceived school
      multiculturalism and subjective happiness with full mediation by ethnocultural
      empathy for African Americans, Asians, males, and females. Although school
      multiculturalism was also predictive of ethnocultural empathy for Hispanics,
      ethnocultural empathy in turn, was not significantly predictive of subjective
      happiness. Taken together, these results suggest that one way to facilitate
      psychological growth and flourishing among ethnic minority youth is to encourage
      multiculturalism in school settings.

PMID- 19594260
TI  - Challenges in researching racially sensitive topics in HMOs.
AB  - When research designed to close the disparities gap is conducted in real-world
      health care settings, unique sensitivities may arise, particularly when race is
      the focus of interventions. Researchers encountered this issue in the course of a
      randomized trial investigating the influence of ethnic identity (EI) among
      African American (AA) study participants. The study was conducted by the research
      programs at three health maintenance organizations (HMOs) and the University of
      Michigan Center for Health Communications Research, as described in this issue of
      the journal (Resnicow et al., 2009). This commentary describes the research
      partnership's concerns for the racially sensitive nature of the study and the
      precautions undertaken to mitigate them. The research study's experiences may be
      informative and insightful for health plans and research centers invested in
      health disparities research.

PMID- 19594261
TI  - Community-based participatory research: partnering with communities for effective
      and sustainable behavioral health interventions.
AB  - The present issue contains one of the first studies published in Health
      Psychology-by Resnicow and colleagues-that uses elements of community-based
      participatory research (CBPR) (Resnicow et al., 2009). The authors engaged
      community partners (three health maintenance organizations or HMOs) to develop
      and implement a fruit and vegetable promotion intervention (Tolsma et al., 2009).
      African American HMO patients (the intervention targets) participated in
      formative work (i.e., focus groups) on survey items and intervention content and
      in survey pilot testing. A diverse group of researcher and nonresearcher expert
      stakeholders (e.g., African American health plan staff; consultants with
      expertise in Black identity theory, on which the intervention was based) was
      engaged in major project decisions regarding the measures and intervention
      design.

PMID- 19594262
TI  - Tailoring a fruit and vegetable intervention on ethnic identity: results of a
      randomized study.
AB  - OBJECTIVE: Many targeted interventions have been developed and tested with
      African Americans (AA); however, AAs are a highly heterogeneous group. One
      characteristic that varies across AAs is Ethnic Identity (EI). Little research
      has been conducted on how to incorporate EI into the design of health messages
      and programs. DESIGN: We tested whether tailoring a print-based fruit and
      vegetable (F & V) intervention on EI would enhance program impact. AA adults were
      recruited from two integrated healthcare delivery systems and then randomized to
      receive three newsletters focused on F & V behavior change over three months. One
      set of newsletters was tailored only on demographic and social cognitive
      variables (control condition), whereas the other (experimental condition) was
      additionally tailored on EI. MAIN OUTCOME MEASURES: The primary outcome for the
      study was F & V intake, assessed at baseline and three months later using the
      composite of two brief self-report frequency measures. RESULTS: A total of 560
      eligible participants were enrolled, of which 468 provided complete 3-month
      follow-up data. The experimental group increased their daily mean F & V intake by
      1.1 servings compared to .8 servings in the control group (p = .13). Afrocentric
      experimental group participants showed a 1.4 increase in F & V servings per day
      compared to a .43 servings per day increase among Afrocentric controls (p < .05).
      CONCLUSIONS: Although the overall between-group effects were not significant,
      tailoring dietary messages on ethnic identity may improve intervention impact for
      some AA subgroups.

PMID- 19594263
TI  - Priming effects of television food advertising on eating behavior.
AB  - OBJECTIVE: Health advocates have focused on the prevalence of advertising for
      calorie-dense low-nutrient foods as a significant contributor to the obesity
      epidemic. This research tests the hypothesis that exposure to food advertising
      during TV viewing may also contribute to obesity by triggering automatic snacking
      of available food. DESIGN: In Experiments 1a and 1b, elementary-school-age
      children watched a cartoon that contained either food advertising or advertising
      for other products and received a snack while watching. In Experiment 2, adults
      watched a TV program that included food advertising that promoted snacking and/or
      fun product benefits, food advertising that promoted nutrition benefits, or no
      food advertising. The adults then tasted and evaluated a range of healthy to
      unhealthy snack foods in an apparently separate experiment. MAIN OUTCOME
      MEASURES: Amount of snack foods consumed during and after advertising exposure.
      RESULTS: Children consumed 45% more when exposed to food advertising. Adults
      consumed more of both healthy and unhealthy snack foods following exposure to
      snack food advertising compared to the other conditions. In both experiments,
      food advertising increased consumption of products not in the presented
      advertisements, and these effects were not related to reported hunger or other
      conscious influences. CONCLUSION: These experiments demonstrate the power of food
      advertising to prime automatic eating behaviors and thus influence far more than
      brand preference alone.

PMID- 19594265
TI  - Perception of others' body size influences weight loss and regain for European
      American but not African American women.
AB  - OBJECTIVE: The authors investigated whether European American (EA) and African
      American (AA) women took longer to lose weight, and were less likely to maintain
      weight loss if they perceived others to be overweight. DESIGN: Overweight EA and
      AA women completed a Figure Rating Scale and the Three-Factor Eating
      Questionnaire prior to a weight loss intervention. Body composition was assessed
      by dual energy X-ray absorptiometry prior to and following weight loss. MAIN
      OUTCOME MEASURES: rate of weight loss, % body fat at follow-up. RESULTS: For EA,
      but not AA women, perception of others' body size was inversely associated with
      rate of weight loss and cognitive restraint, and positively associated with body
      fat gain following intervention. In linear regression modeling, EA, but not AA,
      women who perceived others as large, subsequently had greater percent body fat 1
      year after weight loss than did those who perceived others as lean, independent
      of age, baseline body fat, and body size deemed "acceptable." Inclusion of
      cognitive restraint in the model weakened this effect. CONCLUSION: Among EA but
      not AA women, perception of others' body size influenced weight loss and
      maintenance. This effect may have been mediated by cognitive restraint.

PMID- 19594267
TI  - Parent-child attitude congruence on type and intensity of physical activity:
      testing multiple mediators of sedentary behavior in older children.
AB  - OBJECTIVE: This study examined parent-child attitudes on value of specific types
      and intensities of physical activity, which may explain gender differences in
      child activity, and evaluated physical activity as a mechanism to reduce time
      spent in sedentary behaviors. DESIGN: A community sample of 681 parents and 433
      children (mean age 9.9 years) reported attitudes on importance of vigorous and
      moderate intensity team and individually performed sports/activities, as well as
      household chores. Separate structural models (LISREL 8.7) for girls and boys
      tested whether parental attitudes were related to child TV and computer via child
      attitudes, sport team participation, and physical activity, controlling for
      demographic factors. MAIN OUTCOME MEASURES: Child 7-day physical activity, sport
      teams, weekly TV, computer. RESULTS: Parent-child attitude congruence was more
      prevalent among boys, and attitudes varied by ethnicity, parent education, and
      number of children. Positive parent-child attitudes for vigorous team sports were
      related to increased team participation and physical activity, as well as reduced
      TV and computer in boys and girls. Value of moderate intensity household chores,
      such as cleaning house and doing laundry, was related to decreased team
      participation and increased TV in boys. Only organized team sports, not general
      physical activity, was related to reduced TV and computer. CONCLUSION: Results
      support parents' role in socializing children's achievement task values,
      affecting child activity by transferring specific attitudes. Value of vigorous
      intensity sports provided the most benefits to activity and reduction of
      sedentary behavior, while valuing household chores had unexpected negative
      effects.

PMID- 19594266
TI  - Can the influence of childhood socioeconomic status on men's and women's adult
      body mass be explained by adult socioeconomic status or personality? Findings
      from a national sample.
AB  - OBJECTIVES: On the basis of a life-course risk-chain framework, the authors
      examined whether (a) residual associations between childhood socioeconomic status
      (SES) and adult obesity and body mass index (BMI) would be observed in women but
      not men after adjusting for adult SES, (b) adult Big Five personality traits
      would be associated with adult body mass in both genders, and (c) personality
      would explain unique variation in outcomes beyond child and adult SES. DESIGN:
      National survey (Midlife Development in the United States study; N = 2,922). MAIN
      OUTCOME MEASURES: BMI and obesity. RESULTS: (a) In both genders, association
      between childhood SES and adult obesity were accounted for entirely by adult SES,
      but its effect on adult BMI was observed only in women; (b) higher
      conscientiousness was associated with lower obesity prevalence and BMI in both
      genders, although more strongly in women, and in men, greater obesity prevalence
      was associated with higher agreeableness and neuroticism; and (c) personality
      explained unique outcome variation in both genders. CONCLUSIONS: Early social
      disadvantage may affect adult weight status more strongly in women owing to
      gender differences in the timing and nature of weight-management socialization.
      Personality may enhance or detract from risks incurred by childhood or adulthood
      SES in either gender, necessitating the consideration of dispositional
      differences in prevention and intervention programs.

PMID- 19594268
TI  - Psychological and social risk factors in adolescent smoking transitions: a
      population-based longitudinal study.
AB  - OBJECTIVE: This study longitudinally investigated psychological and social risk
      factors consistent with the Theory of Triadic Influence (TTI) as predictors of
      adolescent smoking transitions. DESIGN: Among 4218 adolescents, five
      psychological risk factors (i.e., parent-noncompliance, friend-compliance,
      rebelliousness, low achievement motivation, and thrill seeking) were assessed in
      9th grade (age 14), two social influence risk factors (i.e., parents' and close
      friends' smoking) were assessed in Grades 3 (age 8) and 9 (age 14), respectively.
      MAIN OUTCOME MEASURES: Adolescent smoking transitions occurring between the 9th
      and 12th (ages 14-17) grade interval. RESULTS: The probabilities contributed by
      each of the five psychological risk factors to the overall probability of making
      a specific smoking transition were: 22% to 27% for the transition from never to
      trying smoking, 10% to 13% for the transition from trying to monthly smoking,
      and, for three of the five risk factors, 11% to 16% for the transition from
      monthly to daily smoking. For predicting trying smoking, the probability
      contributed by these psychological factors was greater than the probability
      contributed by each parent's and close friend's smoking. Parent-compliance had a
      higher contribution to the probability of trying smoking when an adolescent's
      parent smoked (p < .05), whereas friend-compliance had a higher contribution to
      the probability of trying smoking when an adolescent's friend smoked (p < .001).
      CONCLUSION: These psychological and social factors have an important influence on
      adolescent smoking transitions. Implications for TTI and smoking prevention
      interventions are discussed.

PMID- 19594270
TI  - Regret and rationalization among smokers in Thailand and Malaysia: findings from
      the International Tobacco Control Southeast Asia Survey.
AB  - OBJECTIVE: To test whether differences of history and strength in tobacco control
      policies will influence social norms, which, in turn, will influence quit
      intentions, by influencing smokers' regret and rationalization. DESIGN: The data
      were from the International Tobacco Control (ITC) Policy Evaluation Southeast
      Asia Survey, a cohort survey of representative samples of adult smokers in
      Thailand (N = 2,000) and Malaysia (N = 2,006). The survey used a stratified
      multistage sampling design. MAIN OUTCOME MEASURES: Measures included regret,
      rationalization, social norms, and quit intention. RESULTS: Thai smokers were
      more likely to have quit intentions than Malaysian smokers. This difference in
      quit intentions was, in part, explained by the country differences in social
      norms, regret, and rationalization. Reflecting Thailand's history of stronger
      tobacco control policies, Thai smokers, compared with Malaysian smokers,
      perceived more negative social norms toward smoking, were more likely to regret,
      and less likely to rationalize smoking. Mediational analyses revealed that these
      differences in social norms, accounted, in part, for the country-quit intention
      relation and that regret and rationalization accounted, in part, for the social
      norm-quit intention relation. CONCLUSION: The results suggest that social norms
      toward smoking, which are shaped by tobacco control policies, and smokers' regret
      and rationalization influence quit intentions.

PMID- 19594269
TI  - A prospective study of cigarette smoking initiation during college: Chinese and
      Korean American students.
AB  - OBJECTIVE: The present study was a prospective investigation of baseline
      influences on initial smoking and transition to established smoking among college
      students who had not smoked prior to college. DESIGN: Included were 267
      participants in a longitudinal study of tobacco use. Students of Chinese (52%) or
      Korean (48%) descent were enrolled during their freshman year in college. Data
      for the present study were collected during four annual in-person interviews.
      MAIN OUTCOME MEASURES: (1) Initial use of a cigarette reflected having first
      smoked a cigarette (more than a puff) during college. (2) Established smoking was
      defined as having smoked at least 100 cigarettes. RESULTS: Over the course of the
      study, 25% of baseline never-smokers tried their first cigarette, and 9% became
      established smokers. Overall, men were significantly more likely to experiment
      and progress to established smoking. Baseline alcohol and drug use, behavioral
      undercontrol, and parental smoking predicted smoking experimentation but not
      established smoking. Students of Korean ethnicity were more likely to become
      established smokers. However, acculturation was not a significant predictor of
      experimentation or established smoking after accounting for the effects of other
      predictors. CONCLUSION: These findings suggest a need for efforts to prevent
      smoking uptake among Asian American college students.

PMID- 19594271
TI  - Longitudinal analysis of abstinence-specific social support and smoking
      cessation.
AB  - OBJECTIVES: (1) To replicate previous research finding that abstinence-specific
      social support during the active phase of quitting predicts short- and long-term
      smoking cessation treatment outcome. (2) To describe time-related changes in
      abstinence-specific support, including how support provided during middle and
      later phases of the quitting process is associated with treatment outcome.
      DESIGN: Combined data from three randomized clinical trials of smoking cessation
      treatment (N = 739) were analyzed using logistic regression and analysis of
      variance. MAIN OUTCOME MEASURES: Measures included the Partner Interaction
      Questionnaire (PIQ; Cohen & Lichtenstein, 1990), a measure of smoking-related
      social support, and smoking status according to 7-day point-prevalence
      abstinence. RESULTS: Longitudinal analyses found that positive support peaked at
      week 12, decreasing thereafter. Positive support provided after week 12 did not
      differentiate between those who never quit smoking, those who quit and relapsed,
      and those who maintained abstinence. In contrast, negative support was monotonic
      and was useful at follow-up points for distinguishing between outcome groups.
      CONCLUSION: These results suggest that positive and negative support are both
      important factors in the early phase of quitting, but it is the continued
      minimization of negative support that best predicts maintenance of nonsmoking.

PMID- 19594273
TI  - Smokers' thoughts and worries: a study using ecological momentary assessment.
AB  - OBJECTIVE: The purpose of this study was to investigate smokers' thoughts and
      worries about their smoking behavior. Researchers have sometimes asked smokers to
      make such self-assessments but typically using retrospective summary judgments.
      DESIGN: Using ecological momentary assessment, community and student smokers
      reported five times daily during two separate 1-week intervals. MAIN OUTCOME
      MEASURES: Smokers reported their thoughts about smoking, worries about smoking,
      and level of contemplation to quit smoking. RESULTS: Smokers reported thinking
      negatively about their smoking 26.8% of the time they had a cigarette. The most
      frequent thoughts reported by smokers related to immediate reinforcement of
      smoking (e.g., "How I smell like cigarettes"). However, smokers reported more
      intense worry about thoughts related to health concerns (e.g., "Symptoms I'm
      having because of smoking"). The occurrence of negative thoughts was
      significantly and positively related to contemplation about quitting, worry about
      smoking, and risk perceptions. Finally, self-reported worry intensity was more
      strongly related to contemplation of quitting than negative thought occurrence.
      CONCLUSION: Our results show that thoughts about smoking (i.e., cognitions) and
      feelings about smoking (i.e., worry) are loosely connected and it is feelings
      rather than cognitions that are most related to contemplation to quit.

PMID- 19594272
TI  - Watching and drinking: expectancies, prototypes, and friends' alcohol use mediate
      the effect of exposure to alcohol use in movies on adolescent drinking.
AB  - OBJECTIVE: To investigate the psychological processes that underlie the relation
      between exposure to alcohol use in media and adolescent alcohol use. DESIGN: The
      design consisted of a structural equation modeling analysis of data from four
      waves of a longitudinal, nationally representative, random-digit dial telephone
      survey of adolescents in the United States. MAIN OUTCOME MEASURES: The main
      outcome measures were adolescent alcohol consumption and willingness to use
      alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies,
      and friends' use. RESULTS: Alcohol prototypes, expectancies, willingness, and
      friends' use of alcohol (but not perceived prevalence of alcohol use among peers)
      were significant mediators of the relation between movie alcohol exposure and
      alcohol consumption, even after controlling for demographic, child, and family
      factors associated with both movie exposure and alcohol consumption. CONCLUSION:
      Established psychological and interpersonal predictors of alcohol use mediate the
      effects of exposure to alcohol use in movies on adolescent alcohol consumption.
      The findings suggest that exposure to movie portrayals may operate through
      similar processes as other social influences, highlighting the importance of
      considering these exposures in research on adolescent risk behavior.

PMID- 19594274
TI  - An intervention to reduce kerosene-related burns and poisonings in low-income
      South African communities.
AB  - OBJECTIVE: Unintentional injury rates in low- and middle-income countries are up
      to 50 times higher than high-income nations. In South Africa, kerosene (paraffin)
      is a leading cause of poisoning and burns, particularly in low-income communities
      where it serves as a primary fuel for light, cooking, and heating. This study
      tested a community-based intervention to reduce kerosene-related injury risk. The
      intervention used a train-the-trainers model, whereby expert trainers train local
      paraprofessionals, who in turn deliver educational materials to community
      residents. The intervention was theory-driven, pragmatically motivated, and
      culturally sensitive. DESIGN: Prospective quasi-experimental intervention design
      with nonequivalent case versus control groups. MAIN OUTCOME MEASURES: Three
      primary outcome measures were considered: self-reported knowledge of kerosene
      safety, observed practice of safe kerosene use, and self-reported recognition of
      risk for kerosene-related injury. RESULTS: ANOVA models suggest a large and
      significant increase in self-reported kerosene-related knowledge in the
      intervention community compared to the control community. There were smaller, but
      statistically significant changes, in kerosene-related safety practices and
      recognition of kerosene injury risk in the intervention community compared to the
      control community. CONCLUSION: The intervention was successful. A train-the
      trainers model might be an effective educational tool to reduce kerosene-related
      injury risk in low-income communities within low- and middle-income countries.

PMID- 19594275
TI  - Social interaction moderates the relationship between depressive mood and heart
      rate variability: evidence from an ambulatory monitoring study.
AB  - OBJECTIVE: There is considerable evidence that depressive mood is related to
      lower parasympathetic control of the heart, thus increasing cardiovascular risk.
      However, little is known about social factors (e.g., social affiliation) that
      might moderate this relationship. DESIGN: The authors examined whether cardiac
      autonomic control in healthy individuals with depressive symptoms could be
      altered by social interaction. Therefore, the authors conducted a 22-hr
      ambulatory monitoring study with a sample of 63 adults. MAIN OUTCOME MEASURES:
      Depression was assessed by questionnaire. Heart rate, heart rate variability
      (HRV), physical activity, and negative affect were recorded throughout one day
      via portable monitoring devices. RESULTS AND CONCLUSION: Multilevel analyses
      revealed that depression was related to elevated negative affect and higher heart
      rate throughout the day. Moreover, there was a tendency toward lower HRV in
      individuals with higher depression scores. This association, however, was
      moderated by social context. When depressive participants were alone they
      evidenced lower HRV and higher negative affect, but not when they were engaged in
      social interactions with a partner, family members, or friends. These findings
      suggest that the relation between depression and cardiac autonomic control could
      be altered by social interaction, thus possibly buffering adverse health effects.

PMID- 19594276
TI  - Emotional distress following genetic testing for hereditary breast and ovarian
      cancer: a meta-analytic review.
AB  - OBJECTIVE: Meta-analysis was used to synthesize results of studies on emotional
      consequences of predictive genetic testing for BRCA1/2 mutations conferring
      increased risk of breast and ovarian cancer. DESIGN: Studies assessing anxiety or
      cancer-specific distress before and after provision of test results (k = 20) were
      analyzed using a random-effects model. Moderator variables included country of
      data collection and personal cancer history of study participants. MAIN OUTCOME
      MEASURES: Standardized mean gain effect sizes were calculated for mutation
      carriers, noncarriers, and those with inconclusive results over short (0-4
      weeks), moderate (5-24 weeks), or long (25-52 weeks) periods of time after
      testing. RESULTS: Distress among carriers increased shortly after receiving
      results and returned to pretesting levels over time. Distress among noncarriers
      and those with inconclusive results decreased over time. Some distress patterns
      differed in studies conducted outside the United States and for individuals with
      varying cancer histories. CONCLUSION: Results underscore the importance of time;
      changes in distress observed shortly after test-result disclosure frequently
      differed from the pattern of distress seen subsequently. Although emotional
      consequences of this testing appear minimal, it remains possible that testing may
      affect cognitive and behavioral outcomes, which have rarely been examined through
      meta-analysis. Testing may also affect understudied subgroups differently.

PMID- 19594277
TI  - Resistance to change within heterogeneous response sequences.
AB  - Three experiments investigated how instrumental and Pavlovian contingencies
      contribute to resistance to change (RTC) in different ordinal response positions
      within heterogeneous response sequences in pigeons. RTC in the initial and
      terminal response positions of a three-response sequence were compared in
      Experiment 1, which presented three colored key lights in succession in each
      trial; and in Experiment 2, which severely degraded Pavlovian contingencies by
      presenting the lights simultaneously at each ordinal position. Experiment 3
      eliminated the instrumental contingency in a high-order sign-tracking procedure.
      When the instrumental contingency was in effect, RTC of the initial position was
      greater than the terminal position (Initial RTC > Terminal RTC) when the
      Pavlovian contingencies were strong and when they were degraded. When the
      instrumental contingency was eliminated, RTC patterns reversed, producing a
      graded pattern of RTC (Initial < Middle < Terminal). Current theoretical
      approaches (e.g., behavioral momentum theory, conditioned reinforcement, and
      motivational control of instrumental conditioning) cannot account for these
      results. An alternative approach (a gradient model) shows that obtained measures
      of RTC in heterogeneous sequences may reflect a combination of three dissociable
      processes.

PMID- 19594278
TI  - Learned predictiveness effects in humans: a function of learning, performance, or
      both?
AB  - Many previous studies of animal and human learning indicate a processing
      advantage for cues previously experienced as good predictors of outcomes over
      those experienced as poorer predictors. Four studies of human associative
      learning investigated whether learned predictiveness acts at the level of
      learning (modulating the rate at which cue-outcome associations form),
      performance (modulating the strength of behavioral responses), or both. In
      Experiments 1-3, it was found that retrospectively altering the learned
      predictiveness of cues influenced responding to those cues, demonstrating that
      learned predictiveness influences performance. Experiment 4 indicates that
      learned predictiveness also influences learning by demonstrating that the learned
      predictiveness of a cue affects the acquisition of an association between a novel
      cue and the outcome with which it is paired.

PMID- 19594279
TI  - The loss of latent inhibition across compound conditioning.
AB  - Six experiments used a magazine approach paradigm with rats to investigate latent
      inhibition (LI). Experiment 1 found that compound conditioning did not increase
      evidence for LI, in contrast to predictions from acquisition-deficit models that
      are based on a common error term (e.g., J. M. Pearce & G. Hall, 1980; A. R.
      Wagner, 1981). Instead, it appeared that preexposed and non-preexposed stimuli
      conditioned to the same asymptote following compound conditioning, as is the case
      when these stimuli are conditioned separately. This was confirmed in three
      further experiments that used probe trials to measure conditioning to each
      conditioned stimulus across the course of compound training. In these
      experiments, LI was observed during initial but not extended compound training,
      consistent with predictions derived from M. E. Bouton (1997) and the SLG model
      (N. A. Schmajuk, Y. Lam, & J. A. Gray, 1996). However, 2 further experiments did
      not support these models. Instead, these findings are most consistent with models
      that use separate error terms to compute the associative strength of conditioned
      stimuli conditioned in compound (S. E. Brandon, E. H. Vogel, & A. R. Wagner,
      2003; M. E. Le Pelley, 2004; N. J. Mackintosh, 1975).

PMID- 19594280
TI  - Potentiation and overshadowing in Pavlovian fear conditioning.
AB  - The present experiments addressed a fundamental discrepancy in the Pavlovian
      conditioning literature concerning responding to a target cue following compound
      reinforced training with another cue of higher salience. Experiment 1 identified
      one determinant of whether the target cue will be overshadowed or potentiated by
      the more salient cue, namely contiguity between compound CS termination and US
      presentation. Overshadowing and potentiation were observed with delay and trace
      procedures, respectively. Experiments 2 and 3 contrasted elemental and configural
      explanations of potentiation. Both experiments supported a configural account.
      Experiments 3 and 4, by manipulating prior learning experiences to bias subjects
      to encode the same compound elementally or configurally, demonstrated decreased
      potentiation and overshadowing, respectively. Overall, these experiments
      demonstrate potentiation with nontaste stimuli and identify one variable that
      determines whether overshadowing or potentiation will occur. Moreover, they show
      that prior experiences can determine how a compound is encoded and are compatible
      with the idea of flexible encoding as a principle of information processing.

PMID- 19594281
TI  - Absence of overshadowing between a landmark and geometric cues in a distinctively
      shaped environment: a test of Miller and Shettleworth (2007).
AB  - Rats in the first 2 experiments, which were designed to test predictions from a
      model of spatial learning by N. Y. Miller and S. J. Shettleworth (2007), had to
      escape from a triangular pool by swimming to a submerged platform in a
      geometrically unique corner. A spherical landmark was suspended above the
      platform for an overshadowing group. A control group was trained with the same
      arrangement and with a second, identical landmark suspended in another corner.
      The platform could thus be found by reference to the landmark or the geometric
      cues in the overshadowing group, whereas the control group had to rely on
      geometric cues. There was no indication of overshadowing between the geometric
      cues and the landmark in the overshadowing group. The final 2 experiments
      revealed that the absence of overshadowing was not a consequence of the landmark
      being an ineffective cue for overshadowing. The results indicate either that the
      landmark and geometric cues were not in competition for the control they acquired
      over behavior or that an additional process compensated for any such competition
      that might have occurred in the overshadowing group. This additional process
      could involve between-cues associations or the provision of a stable spatial
      framework.

PMID- 19594282
TI  - The psychological organization of "uncertainty" responses and "middle" responses:
      a dissociation in capuchin monkeys (Cebus apella).
AB  - Some studies of nonhuman animals' metacognitive capacity encourage competing low
      level, behavioral descriptions of trial-decline responses by animals in
      uncertainty-monitoring tasks. To evaluate the force of these behavioral
      descriptions, the authors presented 6 capuchin monkeys (Cebus apella) with 2
      density discrimination tasks between sparse and dense stimuli. In one task,
      difficult trials with stimuli near the middle of the density continuum could be
      declined through an "uncertainty" response. In the other task, making a "middle"
      response to the same stimuli was rewarded. In Experiment 1, capuchins essentially
      did not use the uncertainty response, but they did use the middle response. In
      Experiment 2, the authors replicated this result with 5 of 6 monkeys while
      equating the overall pace and reinforcement structure of the 2 tasks, although 1
      monkey also showed appropriate use of the uncertainty response. These results
      challenge a purely associative interpretation of some uncertainty-monitoring
      performances by monkeys while sharpening the theoretical question concerning the
      nature of the psychological signal that occasions uncertainty responses.

PMID- 19594283
TI  - Resolution of conflict between goal-directed actions: outcome encoding and neural
      control processes.
AB  - According to O-R theory of instrumental learning, incongruent biconditional
      discriminations should be impossible to solve in a goal-directed manner because
      the event acting as the outcome of one response also acts as a discriminative
      stimulus for an opposite response. Each event should therefore be associated with
      two competing responses. However, Dickinson and de Wit (2003) have presented
      evidence that rats can learn incongruent discriminations. The present study
      investigated whether rats were able to engage additional processes to solve
      incongruent discriminations in a goal-directed manner. Experiment 1 provides
      evidence that rats resolve the response conflict that arises in the incongruent
      discrimination by differentially encoding events in their roles as discriminative
      stimulus and as outcome. Furthermore, Experiment 2 shows that once goal-directed
      control has been established the dorsomedial prefrontal cortex is not directly
      involved in its maintenance but rather plays a central role in conflict
      resolution processes.

PMID- 19594284
TI  - Early maternal separation increases symptoms of activity-based anorexia in male
      and female rats.
AB  - Running activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing the
      release of stress hormones known to exert anorexic effects. HPA axis reactivity
      is strongly influenced by early postnatal manipulations, including removal of
      pups from the dam for short (handling) or prolonged (maternal separation)
      durations during the preweaning period. The authors examined the effects of
      handling and maternal separation on food intake, body weight loss, and running
      rates of young adult male and female rats in the activity-based anorexia (ABA)
      paradigm. Postnatal treatment did not affect adaptation to a 1-hr restricted
      feeding schedule before the introduction of wheel running. During the ABA
      paradigm, maternally separated animals lost weight faster, ate less, ran more,
      and required fewer days to reach removal criterion compared with handled rats.
      Females were particularly vulnerable. These findings indicate that early
      postnatal treatment and sex influence ABA.

PMID- 19594285
TI  - Attentional and error-correcting associative mechanisms in classical
      conditioning.
AB  - R. A. Rescorla (2000, Rescorla, 2001, Rescorla, 2002) reported that the
      associative changes undergone by 2 conditioned stimuli that are reinforced or not
      reinforced in compound depend on their initial associations. The results
      contradict the predictions of simple error-correction models but can be explained
      by models that incorporate a "constrained" error-correction rule. A model of
      classical conditioning presented by N. A. Schmajuk, Y. Lam, and J. A. Gray (1996)
      suggests that attentional mechanisms, acting during both compound training and
      testing, have an important role in producing those results. Moreover, the model
      suggests that those attentional mechanisms might obscure the evaluation of the
      associative changes undergone by the conditioned stimuli during compound
      training. Two experiments that differentiate our model from competing theories
      are proposed.

PMID- 19594286
TI  - Spontaneous recovery of excitation and inhibition.
AB  - In two conditioned suppression experiments with rats as subjects, the authors
      examined two classes of accounts of spontaneous recovery of excitation and
      inhibition. One view suggests that spontaneous recovery occurs due to greater
      temporal instability of inhibitory associations, whereas the other posits that
      spontaneous recovery occurs due to greater temporal instability of second-learned
      associations. These accounts diverge in predictions concerning spontaneous
      recovery when the first-learned association is inhibitory and the second-learned
      association is excitatory. Using different designs, Experiments 1 and 2 found
      spontaneous recovery of both excitation and inhibition. The results support the
      view that spontaneous recovery occurs due to faster waning of second-learned
      associations.

PMID- 19594287
TI  - Hysteresis effects in a motor task with cotton-top tamarins (Sanguinus oedipus).
AB  - The way human adults grasp an object is influenced by their recent history of
      motor actions. Previously executed grasps are often more likely to reoccur on
      subsequent grasps. This type of hysteresis effect has been incorporated into
      cognitive models of motor planning, suggesting that when planning movements,
      individuals tend to reuse recently used plans rather than generating new plans
      from scratch. To the best of our knowledge, the phylogenetic roots of this
      phenomenon have not been investigated. Here, the authors asked whether 6 cotton
      top tamarin monkeys (Saguinus oedipus) would demonstrate a hysteresis effect on a
      reaching task. The authors tested the monkeys by placing marshmallow pieces
      within grasping distance of a hole through which the monkeys could reach. On
      subsequent trials, the marshmallow position changed such that it progressed in an
      arc in either a clockwise or counterclockwise direction. The authors asked
      whether the transition point in right- versus left-handed reaches would differ
      depending on the direction of the progression. The data supported this hysteresis
      prediction. The outcome provides additional support for the notion that human
      motor planning strategies may have a lengthy evolutionary history.

PMID- 19594288
TI  - Averaging of temporal memories by rats.
AB  - Rats were trained on a mixed fixed-interval schedule in which stimulus A (tone or
      light) indicated food availability after 10 s and stimulus B (the other stimulus)
      indicated food availability after 20 s. Testing consisted of nonreinforced probe
      trials in which the stimulus was A, B, or the compound AB. On single-stimulus
      trials, rats responded with a peak of activity around the programmed reinforced
      time. On compound-stimulus trials, rats showed a single scalar peak of responding
      at a time midway between those for stimulus A and B. These results suggest that
      when provided with discrepant information regarding the temporal predictability
      of reinforcement, rats compute an average of the scheduled reinforcement times
      for the A and B stimuli and use this average to generate an expectation of reward
      for the compound stimuli.

PMID- 19594289
TI  - Learning about associations: evidence for a hierarchical account of occasion
      setting.
AB  - In 2 experiments rats were trained on a switching discrimination, with 4 occasion
      setters, A, B, C, and D and 2 target stimuli, x and y. When signaled either by A
      or by B, x was reinforced with food and y was not, whereas when signaled either
      by C or by D these reinforcement relations were reversed (i.e., A: --> x+, A: y -
      > -, B: x --> +, B: y --> -, C: x --> -, C: y --> +, D: x --> -, D: y --> +). In
      a subsequent Stage A was paired with shock, and then the degree to which food
      reinforced (Experiment 1a) and nonreinforced (Experiment 1b) presentations of x
      and y were capable of eliciting fear was assessed. Those conditioned stimulus
      (CS)/unconditioned stimulus (US) relations that had been operative in the
      presence of the fear-eliciting occasion setter A (i.e., x --> +, y --> -)
      elicited more fear than the alternative CS/US combinations (i.e., x --> -, y -->
      +). The implications of these findings are discussed with reference to theories
      of occasion setting and of configural learning.

PMID- 19594290
TI  - Rural residence and prostate cancer screening with prostate-specific antigen.
AB  - Prostate cancer mortality worldwide has recently decreased by 6% after peaking in
      the 1990s. Based on the recently published results of the European Randomised
      Study for Screening of Prostate Cancer (which showed a relative prostate cancer
      mortality reduction of at least 20% by PSA-based population screening) it could
      be assumed that this decrease is in part due to the implementation of prostate
      specific antigen (PSA) screening. The existing large rural-urban inequality in
      prostate cancer mortality rates can be now associated with the different rates of
      prostate cancer screening between men who live in capital cities and men who live
      in regional and rural areas. Given the adverse effects of PSA-based prostate
      cancer screening in terms of over-diagnosis and over-treatment, research is
      needed to develop effective methods for cancer prevention and early detection
      services in rural populations. In the meantime, the introduction of intervention
      strategies is needed to augment existing prostate cancer screening methods.

PMID- 19594291
TI  - What older people want: evidence from a study of remote Scottish communities.
AB  - INTRODUCTION: The growing proportions of older people in rural areas have
      implications for the provision of health and social care services. Older people
      are more likely to have complex health needs compared with other age groups,
      requiring a full range of primary, community and acute hospital services. The
      provision of services to older people in rural areas is challenged by
      diseconomies of scale, travel costs and difficulties in attracting staff. Policy
      makers are requested to include the 'voice' of older people to help provide
      services that match needs and context. In spite of this, what older people want
      from health and social care services is a neglected area of investigation. The
      reported study was conducted in 2005/2006 as part of a European Union Northern
      Periphery Programme (EU NPP) project called Our Life as Elderly. Its aims were to
      explore the views of those aged 55 years and over and living in remote
      communities about current and future health and social care service provision for
      older people. Evidence was to be collected that could inform policy-makers about
      changing or improving service delivery. This article summarises emergent themes
      and considers their implications. METHODS: The study selected two small remote
      mainland Scottish Highland communities for in-depth case study. Semi-structured
      interviews (n = 23), 10 'informal conversations' and 4 focus groups were held
      with community members aged 55 years and over, in order to provide different
      types of qualitative data and 'layers' of data to allow reflection. Data analysis
      was assisted by computerised data management software and performed using the
      'framework analysis' approach. RESULTS: Participants did not consider themselves
      'old' and expressed the need for independence in older age to be supported by
      services. Several aspects of services that were undergoing change or
      restructuring were identified, including arrangements for home care services,
      meals provision and technological support. Participants valued elements of the
      traditional model of care they had been receiving: these were local, personal
      emphasis and continuity. They were suspicious of new arrangements perceived to
      emphasise technical efficiency. Health and care services were described as inter
      linked with other aspects of rural living, including transport and housing (which
      might have to be relinquished to pay for care). Proximity to family was desired
      for social and domestic support only; health and related support should be from
      generic service providers. Community members were involved in reciprocal help
      giving of many types. CONCLUSION: The findings compare with results of other
      studies of older rural people internationally, and generic 'principles' of
      service derived could guide restructuring. There may be systemic challenges to
      empowering older people's 'voice' in designing sustainable rural services that
      stem from society's views of older people, attitudes of communities to collective
      roles and responsibilities, and the fragmented ways that services are sometimes
      provided.

PMID- 19594292
TI  - Radiographic texture analysis of densitometric calcaneal images: relationship to
      clinical characteristics and to bone fragility.
AB  - Osteoporotic fractures are related not only to bone mineral density (BMD) but
      also to bone structure or microarchitecture, which is not assessed routinely with
      currently available methods. We have developed radiographic texture analysis
      (RTA) for calcaneal images from a peripheral densitometer as an easy, noninvasive
      method for assessing bone structure. We conducted a cross-sectional study of the
      relationship between RTA and prevalent vertebral fractures (n = 148) among 900
      subjects (ages 19 to 99 years, 94 males) referred for bone densitometry as part
      of their routine medical care. RTA features were derived from Fourier-based image
      analysis of the radiographic texture pattern (including root mean square, first
      moment, and power spectral analyses). RTA features were associated with age,
      weight, gender, and race, as well as glucocorticoid use. When controlling for
      clinical risk factors and BMD (or a summary measure calculated using FRAX
      algorithms), RTA features were significantly different for subjects with and
      without prevalent vertebral fractures [adjusted odds ratio (OR) = 1.5 per 1
      standard deviation (SD) decrease in RTA feature beta, 95% confidence interval
      (CI) 1.2-1.8, p = .001]. Gender and use of pharmacologic therapy for osteoporosis
      did not significantly affect this association, suggesting that RTA can be applied
      to a wide range of densitometry patients. We conclude that RTA obtained using a
      portable instrument has a potential as a noninvasive method to enhance
      identification of patients at increased risk of osteoporotic fractures.

PMID- 19594293
TI  - Effects of denosumab on bone mineral density and bone turnover in postmenopausal
      women transitioning from alendronate therapy.
AB  - Patients treated with bisphosphonates for osteoporosis may discontinue or require
      a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor
      of bone resorption that has been shown to increase bone mineral density (BMD) and
      decrease fracture risk in postmenopausal women with osteoporosis. This was a
      multicenter, international, randomized, double-blind, double-dummy study in 504
      postmenopausal women > or = 55 years of age with a BMD T-score of -2.0 or less
      and -4.0 or more who had been receiving alendronate therapy for at least 6
      months. Subjects received open-label branded alendronate 70 mg once weekly for 1
      month and then were randomly assigned to either continued weekly alendronate
      therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12
      months. Changes in BMD and biochemical markers of bone turnover were evaluated.
      In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month
      12 compared with a 1.05% increase in subjects continuing on alendronate (p <
      .0001). Significantly greater BMD gains with denosumab compared with alendronate
      also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius
      (all p < .0125). Median serum CTX levels remained near baseline in the
      alendronate group and were significantly decreased versus alendronate (p < .0001)
      at all time points with denosumab. Adverse events and serious adverse events were
      balanced between groups. No clinical hypocalcemic adverse events were reported.
      Transition to denosumab produced greater increases in BMD at all measured
      skeletal sites and a greater reduction in bone turnover than did continued
      alendronate with a similar safety profile in both groups.

PMID- 19594294
TI  - The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone
      formation.
AB  - The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) interacts with
      a diverse array of transcription factors and regulates a variety of cellular
      events such as cell proliferation, differentiation, and metabolism. However, the
      role of SHP in bone formation has not yet been elucidated. SHP expression is
      significantly increased during osteoblast differentiation, and its expression is
      partially regulated by bone morphogenetic protein 2 (BMP-2), which plays an
      important role in bone formation. In our study, inhibition of SHP expression
      significantly repressed BMP-2-induced osteoblast differentiation and ectopic bone
      formation. In accordance with these in vitro and in vivo results, osteoblast
      differentiation in SHP(-/-) mice primary osteoblasts was significantly repressed,
      and the mice showed decreased bone mass resulting from decreased numbers of
      osteoblasts. Finally, SHP physically interacts and forms a complex with runt
      related transcription factor 2 (Runx2) on the osteocalcin gene promoter, and
      overexpression of SHP increased Runx2 transactivity via competition with histone
      deacetylase 4 (HDAC4), an enzyme that inhibits DNA binding of Runx2 to its target
      genes. Taken together, these results indicate that SHP acts as a novel positive
      regulator of bone formation by augmenting osteoblast differentiation through
      regulation of the transcriptional activity of Runx2.

PMID- 19594295
TI  - Overexpression of secreted frizzled-related protein 1 inhibits bone formation and
      attenuates parathyroid hormone bone anabolic effects.
AB  - Secreted frizzled-related protein 1 (sFRP1) is an antagonist of Wnt signaling, an
      important pathway in maintaining bone homeostasis. In this study we evaluated the
      skeletal phenotype of mice overexpressing sFRP1 (sFRP1 Tg) and the interaction of
      parathyroid hormone (PTH) treatment and sFRP1 (over)expression. Bone mass and
      microarchitecture were measured by micro-computed tomography (microCT).
      Osteoblastic and osteoclastic cell maturation and function were assessed in
      primary bone marrow cell cultures. Bone turnover was assessed by biochemical
      markers and dynamic bone histomorphometry. Real-time PCR was used to monitor the
      expression of several genes that regulate osteoblast maturation and function in
      whole bone. We found that trabecular bone mass measurements in distal femurs and
      lumbar vertebral bodies were 22% and 51% lower in female and 9% and 33% lower in
      male sFRP1 Tg mice, respectively, compared with wild-type (WT) controls at 3
      months of age. Genes associated with osteoblast maturation and function, serum
      bone formation markers, and surface based bone formation were significantly
      decreased in sFRP1 Tg mice of both sexes. Bone resorption was similar between
      sFRP1 Tg and WT females and was higher in sFRP1 Tg male mice. Treatment with
      hPTH(1-34) (40 microg/kg/d) for 2 weeks increased trabecular bone volume in WT
      mice (females: +30% to 50%; males: +35% to 150%) compared with sFRP1 Tg mice
      (females: +5%; males: +18% to 54%). Percentage increases in bone formation also
      were lower in PTH-treated sFRP1 Tg mice compared with PTH-treated WT mice. In
      conclusion, overexpression of sFRP1 inhibited bone formation as well as
      attenuated PTH anabolic action on bone. The gender differences in the bone
      phenotype of the sFRP1 Tg animal warrants further investigation.

PMID- 19594296
TI  - Variable bone fragility associated with an Amish COL1A2 variant and a knock-in
      mouse model.
AB  - Osteogenesis imperfecta (OI) is a heritable form of bone fragility typically
      associated with a dominant COL1A1 or COL1A2 mutation. Variable phenotype for OI
      patients with identical collagen mutations is well established, but phenotype
      variability is described using the qualitative Sillence classification.
      Patterning a new OI mouse model on a specific collagen mutation therefore has
      been hindered by the absence of an appropriate kindred with extensive
      quantitative phenotype data. We benefited from the large sibships of the Old
      Order Amish (OOA) to define a wide range of OI phenotypes in 64 individuals with
      the identical COL1A2 mutation. Stratification of carrier spine (L1-4) areal bone
      mineral density (aBMD) Z-scores demonstrated that 73% had moderate to severe
      disease (less than -2), 23% had mild disease (-1 to -2), and 4% were in the
      unaffected range (greater than -1). A line of knock-in mice was patterned on the
      OOA mutation. Bone phenotype was evaluated in four F(1) lines of knock-in mice
      that each shared approximately 50% of their genetic background. Consistent with
      the human pedigree, these mice had reduced body mass, aBMD, and bone strength.
      Whole-bone fracture susceptibility was influenced by individual genomic factors
      that were reflected in size, shape, and possibly bone metabolic regulation. The
      results indicate that the G610C OI (Amish) knock-in mouse is a novel
      translational model to identify modifying genes that influence phenotype and for
      testing potential therapies for OI.

PMID- 19594297
TI  - Relation of serum serotonin levels to bone density and structural parameters in
      women.
AB  - Recent studies have demonstrated an important role for circulating serotonin in
      regulating bone mass in rodents. In addition, patients treated with selective
      serotonin reuptake inhibitors (SSRIs) have reduced areal bone mineral density
      (aBMD). However, the potential physiologic role of serotonin in regulating bone
      mass in humans remains unclear. Thus we measured serum serotonin levels in a
      population-based sample of 275 women and related these to total-body and spine
      aBMD assessed by dual-energy X-ray absorptiometry, femur neck total and
      trabecular volumetric BMD (vBMD) and vertebral trabecular vBMD assessed by
      quantitative computed tomography (QCT), and bone microstructural parameters at
      the distal radius assessed by high-resolution peripheral QCT (HRpQCT). Serotonin
      levels were inversely associated with body and spine aBMD (age-adjusted R = -0.17
      and -0.16, P < .01, respectively) and with femur neck total and trabecular vBMD
      (age-adjusted R = -0.17 and -0.25, P < .01 and < .001, respectively) but not
      lumbar spine vBMD. Bone volume/tissue volume, trabecular number, and trabecular
      thickness at the radius were inversely associated with serotonin levels (age
      adjusted R = -0.16, -0.16, and -0.14, P < .05, respectively). Serotonin levels
      also were inversely associated with body mass index (BMI; age-adjusted R = -0.23,
      P < .001). Multivariable models showed that serotonin levels remained significant
      negative predictors of femur neck total and trabecular vBMD, as well as
      trabecular thickness at the radius, after adjusting for age and BMI.
      Collectively, our data provide support for a physiologic role for circulating
      serotonin in regulating bone mass in humans.

PMID- 19594298
TI  - Clinical risk factors for osteoporotic fracture: a population-based prospective
      cohort study in Korea.
AB  - Clinical risk factors (CRFs), either alone or in combination with bone mineral
      density, are used to determine the fracture risk for clinical assessment and to
      determine intervention thresholds. Because fracture risk is strongly affected by
      ethnicity and population-specific differences, we sought to identify Korean
      specific CRFs for fracture, in combination with quantitative ultrasound (qUS)
      measurements of the radius and tibia. A total of 9351 subjects (4732 men and 4619
      women) aged 40 to 69 years were followed for a mean of 46.3 +/- 2.2 months. We
      obtained CRF information using a standardized questionnaire and measured
      anthropometric variables. Speed of sound at the radius (SoSR) and tibia (SoST)
      were measured by qUS. Fracture events were recorded using a questionnaire, and a
      height-loss threshold was used as an indicator of vertebral fracture. Relative
      risks were calculated by Cox regression analysis. A total of 195 subjects (61 men
      and 134 women) suffered low-trauma fractures. Older age, lower body mass index
      (BMI), and previous fracture history were positively associated with fracture
      risk in both sexes. Decreased hip circumference, lack of regular exercise, higher
      alcohol intake, menopause, and osteoarthritis history were further independent
      CRFs for fracture in women. However, neither SoSR nor SoST was independently
      associated with fracture risk. In this study, we identified the major Korean
      specific CRFs for fracture and found that smaller hip circumference was a novel
      risk factor. This information will allow optimal risk-assessment targeting
      Koreans for whom treatment would provide the greatest benefit.

PMID- 19594300
TI  - Association of interleukin-15-induced peripheral immune activation with hepatic
      stellate cell activation in persons coinfected with hepatitis C virus and HIV.
AB  - Hepatic stellate cells (HSCs) mediate hepatitis C virus (HCV)-related liver
      fibrosis, and increased HSC activation in human immunodeficiency virus (HIV)/HCV
      coinfection may be associated with accelerated fibrosis. We examined the level of
      HSC activation in HIV/HCV-coinfected and HCV-monoinfected subjects and its
      relationship to the level of activation and gene expression of peripheral immune
      cells in coinfected subjects. HSC activation levels positively correlated with
      peripheral CD4+ and CD8+ T cell immune activation and were associated with
      enhanced interleukin-15 (IL-15) gene expression, suggesting a pathogenic role for
      IL-15-driven immunomediated hepatic fibrosis. Future strategies that reduce
      immune activation and HSC activation may delay progression of liver fibrosis.

PMID- 19594299
TI  - Gene expression profiling in monocytes and SNP association suggest the importance
      of the STAT1 gene for osteoporosis in both Chinese and Caucasians.
AB  - Osteoporosis is characterized mainly by low bone mineral density (BMD). Many
      cytokines and chemokines have been related with bone metabolism. Monocytes in the
      immune system are important sources of cytokines and chemokines for bone
      metabolism. However, no study has investigated in vivo expression of a large
      number of various factors simultaneously in human monocytes underlying
      osteoporosis. This study explored the in vivo expression pattern of general
      cytokines, chemokines, and their receptor genes in human monocytes and validated
      the significant genes by qRT-PCR and genetic association analyses. Expression
      profilings were performed in monocyte samples from 26 Chinese and 20 Caucasian
      premenopausal women with discordant BMD. Genome-wide association analysis with
      BMD variation was conducted in 1000 unrelated Caucasians. We selected 168
      cytokines, chemokines, osteoclast-related factors, and their receptor genes for
      analyses. Significantly, the signal transducer and activator of transcription 1
      (STAT1) gene was upregulated in the low versus the high BMD groups in both
      Chinese and Caucasians. We also revealed a significant association of the STAT1
      gene with BMD variation in the 1000 Caucasians. Thus we conclude that the STAT1
      gene is important in human circulating monocytes in the etiology of osteoporosis.

PMID- 19594301
TI  - Bone mass and strength in older men with type 2 diabetes: the Osteoporotic
      Fractures in Men Study.
AB  - The effects of type 2 diabetes mellitus (T2DM) on bone volumetric density, bone
      geometry, and estimates of bone strength are not well established. We used
      peripheral quantitative computed tomography (pQCT) to compare tibial and radial
      bone volumetric density (vBMD, mg/cm(3)), total (ToA, mm(2)) and cortical (CoA,
      mm(2)) bone area and estimates of bone compressive and bending strength in a
      subset (n = 1171) of men (> or =65 years of age) who participated in the
      multisite Osteoporotic Fractures in Men (MrOS) study. Analysis of covariance
      adjusted bone data for clinic site, age, and limb length (model 1) and further
      adjusted for body weight (model 2) were used to compare data between participants
      with (n = 190) and without (n = 981) T2DM. At both the distal tibia and radius,
      patients with T2DM had greater bone vBMD (+2% to +4%, model 1, p < .05) and a
      smaller bone area (ToA -1% to -4%, model 2, p < .05). The higher vBMD compensated
      for lower bone area, resulting in no differences in estimated compressive bone
      strength at the distal trabecular bone regions. At the mostly cortical bone
      midshaft sites of the radius and tibia, men with T2DM had lower ToA (-1% to -3%,
      p < .05), resulting in lower bone bending strength at both sites after adjusting
      for body weight (-2% to -5%, p < .05) despite the lack of difference in cortical
      vBMD at these sites. These data demonstrate that older men with T2DM have bone
      strength that is low relative to body weight at the cortical-rich midshaft of the
      radius despite no difference in cortical vBMD.

PMID- 19594302
TI  - Prospective assessment of thoracic kyphosis in postmenopausal women with
      osteoporosis.
AB  - We attempt to assess quantitatively thoracic kyphosis and its influence on
      incident fractures and quality of life over three years in postmenopausal women
      with osteoporosis and the effect of strontium ranelate on thoracic kyphosis
      progression. This study was performed on women with postmenopausal osteoporosis
      from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and Treatment of
      Peripheral Osteoporosis (TROPOS) studies. Vertebral fractures were assessed on
      lateral thoracic radiographs performed at baseline and at three years according
      to standardized procedure. Kyphosis index (KI, %), was defined as the percentage
      ratio between the maximum depth of thoracic curvature and the height measured
      from the T4 to the T12 vertebrae. Baseline characteristics of the 3218 patients
      (1594 strontium ranelate, 1624 placebo) were mean age 73.3 years, spine bone
      mineral density (BMD) T-score (L2-4) -3.1, femoral neck T-score -3.0, and KI
      25.4%. In the placebo group, patients with the highest baseline KI experienced
      significantly more vertebral fractures than those with medium KIs [relative risk
      (RR) = 1.53; 95% confidence interval (CI) 1.19-1.96, p < .001) or the lowest KIs
      (RR = 1.70, 95%CI 1.32-2.21, p < .001), even after adjusting for the presence of
      prevalent fractures, age, body mass index (BMI), and BMD. There was no difference
      in the risk of nonvertebral fractures according to baseline KI. Three-year
      changes in quality-of-life physical scores reflected significantly better status
      for patients in the lowest tertile of KI compared with those in the highest at
      baseline. Over three years, the KI increased for all patients, indicating
      worsening of thoracic kyphosis, whatever the presence of prevalent or incident
      vertebral fractures. This KI progression was lower in the strontium ranelate
      group than in the placebo group. Thoracic kyphosis is a risk factor for vertebral
      fractures over three years and influences physical capacity changes in
      postmenopausal women with osteoporosis. Thoracic kyphosis progression over three
      years is lower in a subgroup of strontium ranelate-treated patients compared with
      placebo-treated patients.

PMID- 19594303
TI  - Bone mineralization defects and vitamin D deficiency: histomorphometric analysis
      of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients.
AB  - Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we
      reasoned that a histomorphometric analysis of iliac crest biopsies would be
      another and even more direct approach to assess bone health and address the
      required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern
      European population with its known high prevalence of vitamin D deficiency
      therefore would be ideal to answer the latter question. We examined 675 iliac
      crest biopsies from male and female individuals, excluding all patients who
      showed any signs of secondary bone diseases at autopsy. Structural
      histomorphometric parameters, including osteoid indices, were quantified using
      the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels
      were measured for all patients. Statistical analysis was performed by Student's t
      test. The histologic results demonstrate an unexpected high prevalence of
      mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15%
      of the analyzed patients presented with an osteoid surface per bone surface
      (OS/BS) of more than 20%. Based on the most conservative threshold that defines
      osteomalacia at the histomorphometric level with a pathologic increase in osteoid
      volume per bone volume (OV/BV) greater than 2% manifest mineralization defects
      were present in 25.63% of the patients. The latter were found independent of bone
      volume per trabecular volume (BV/TV) throughout all ages and affected both sexes
      equally. While we could not establish a minimum 25(OH)D level that was inevitably
      associated with mineralization defects, we did not find pathologic accumulation
      of osteoid in any patient with circulating 25(OH)D above 75 nmol/L. Our data
      demonstrate that pathologic mineralization defects of bone occur in patients with
      a serum 25(OH)D below 75 nmol/L and strongly argue that in conjunction with a
      sufficient calcium intake, the dose of vitamin D supplementation should ensure
      that circulating levels of 25(OH)D reach this minimum threshold (75 nmol/L or 30
      ng/mL) to maintain skeletal health.

PMID- 19594305
TI  - Teriparatide for acceleration of fracture repair in humans: a prospective,
      randomized, double-blind study of 102 postmenopausal women with distal radial
      fractures.
AB  - Animal experiments show a dramatic improvement in skeletal repair by
      teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20
      microg dose normally used for osteoporosis treatment or higher, would accelerate
      fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had
      sustained a dorsally angulated distal radial fracture in need of closed reduction
      but no surgery were randomly assigned to 8 weeks of once-daily injections of
      placebo (n = 34) or teriparatide 20 microg (n = 34) or teriparatide 40 microg (n
      = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning
      with the teriparatide 40 microg versus placebo comparison, using a gatekeeping
      strategy. The estimated median time from fracture to first radiographic evidence
      of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8
      weeks for placebo and teriparatide 20 microg and 40 microg, respectively (overall
      p = .015). There was no significant difference between the teriparatide 40 microg
      versus placebo groups (p = .523). In post hoc analyses, there was no significant
      difference between teriparatide 40 microg versus 20 microg (p = .053); however,
      the time to healing was shorter in teriparatide 20 microg than placebo (p =
      .006). The primary hypothesis that teriparatide 40 microg would shorten the time
      to cortical bridging was not supported. The shortened time to healing for
      teriparatide 20 microg compared with placebo still may suggest that fracture
      repair can be accelerated by teriparatide, but this result should be interpreted
      with caution and warrants further study.

PMID- 19594306
TI  - Effect of metformin on bone marrow progenitor cell differentiation: in vivo and
      in vitro studies.
AB  - Diabetes mellitus is associated with bone loss. Patients with type 2 diabetes are
      frequently treated with oral antidiabetic drugs such as sulfonylureas,
      biguanides, and thiazolidinediones. Rosiglitazone treatment has been shown to
      increase adipogenesis in bone marrow and to induce bone loss. In this study we
      evaluated the effect of in vivo and in vitro treatment with metformin on bone
      marrow progenitor cells (BMPCs), as well as the involvement of AMPK pathway in
      its effects. The in vitro effect of coincubation with metformin and rosiglitazone
      on the adipogenic differentiation of BMPCs also was studied. In addition, we
      evaluated the effect of in vivo metformin treatment on bone regeneration in a
      model of parietal lesions in nondiabetic and streptozotocin-induced diabetic
      rats. We found that metformin administration both in vivo and in vitro caused an
      increase in alkaline phosphatase activity, type I collagen synthesis, osteocalcin
      expression, and extracellular calcium deposition of BMPCs. Moreover, metformin
      significantly activated AMPK in undifferentiated BMPCs. In vivo, metformin
      administration enhanced the expression of osteoblast-specific transcription
      factor Runx2/Cbfa1 and activation of AMPK in a time-dependent manner. Metformin
      treatment also stimulated bone lesion regeneration in control and diabetic rats.
      In vitro, metformin partially inhibited the adipogenic actions of rosiglitazone
      on BMPCs. In conclusion, our results indicate that metformin causes an osteogenic
      effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK
      activation, suggesting a possible action of metformin in a shift toward the
      osteoblastic differentiation of BMPCs.

PMID- 19594304
TI  - Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and
      deficient mice.
AB  - Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic
      principle that suppresses expression of the bone formation inhibitor Sost. We
      addressed the relevance of Sost suppression for PTH-induced bone anabolism in
      vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing
      and 2-month-old Sost deficient male mice and their wild-type littermates were
      subjected to daily injections of 100 microg/kg PTH(1-34) or vehicle for a 2-month
      period. A follow-up study was performed in Sost deficient mice using 40 and 80
      microg/kg PTH(1-34). Animals were sacrificed 4 hours after the final PTH
      administration and Sost expression in long bone diaphyses was determined by qPCR.
      Bone changes were analyzed in vivo in the distal femur metaphysis by pQCT and ex
      vivo in the tibia and lumbar spine by DXA. Detailed ex vivo analyses of the femur
      were performed by pQCT, microCT, and histomorphometry. Overexpression of Sost
      resulted in osteopenia and Sost deletion in high bone mass. As shown before, PTH
      suppressed Sost in wild-type mice. PTH treatment induced substantial increases in
      bone mineral density, content, and cortical thickness and in aging wild-type mice
      also led to cancellous bone gain owing to amplified bone formation rates. PTH
      induced bone gain was blunted at all doses and skeletal sites in Sost
      overexpressing and deficient mice owing to attenuated bone formation rates,
      whereas bone resorption was not different from that in PTH-treated wild-type
      controls. These data suggest that suppression of the bone formation inhibitor
      Sost by intermittent PTH treatment contributes to PTH bone anabolism.

PMID- 19594309
TI  - Reevaluation of a tetraploid wheat population indicates that the Tsn1-ToxA
      interaction is the only factor governing Stagonospora nodorum blotch
      susceptibility.
AB  - The wheat Tsn1 gene on chromosome 5B confers sensitivity to a host-selective
      toxin produced by the pathogens that cause tan spot and Stagonospora nodorum
      blotch (SNB) known as Ptr ToxA and SnToxA, respectively (hereafter referred to as
      ToxA). A compatible Tsn1-ToxA interaction is known to play a major role in
      conferring susceptibility of hexaploid (common) wheat to SNB. However, a recent
      study by another group suggested that the Tsn1-ToxA interaction was not relevant
      in conferring susceptibility of the tetraploid (durum) wheat cv. Langdon (LDN).
      Here, we reevaluated the role of the Tsn1-ToxA interaction in governing SNB
      susceptibility using the same mapping population and Stagonospora nodorum isolate
      (Sn2000) as were used in the previous study. Results of our quantitative trait
      locus analysis showed that the Tsn1 locus accounted for 95% of the variation in
      SNB. In addition, inoculation of the mapping population with two ToxA-knockout
      strains of Sn2000 revealed that the entire population was resistant. Furthermore,
      several LDN Tsn1-disrupted mutants were evaluated and found to be resistant to
      SNB. Together, these results prove unequivocally that Tsn1 is the only factor
      present along chromosome 5B that governs response to SNB in this population and
      that a compatible Tsn1-ToxA interaction is necessary for the manifestation of
      disease. Therefore, the results from the previous study are refuted.

PMID- 19594308
TI  - Characterization of rice blast resistance genes in the Pik cluster and fine
      mapping of the Pik-p locus.
AB  - Pik-p is carried by cv. K60, which is one of the Japanese differentials widely
      used in both Japan and China since the 1980s. Its utility and specificity was
      evaluated with a total of 612 isolates of Magnaporthe oryzae collected from
      various regions in China in combination with 16 main resistance genes being used
      in the breeding programs. Pik-p is an independently and dominantly acting gene in
      the Pik cluster, which conditions differential reactions against many isolates
      and contains higher resistance in Guangdong, Jiangsu, and Sichuan provinces,
      China, indicating that this gene could be still used in these regions. A high
      resolution genetic map of Pik-p was constructed using genomic position-ready
      markers. A set of 47 recombinants out of 681 F(2) plants derived from the crosses
      cv. K60 (resistant) x cv. AS20-1 (susceptible) and x cv. Kasalath (susceptible)
      was identified in the genetic interval defined by the markers RM5926 and K37
      which flank the Pik gene cluster. This set was then genotyped with seven markers
      known to reside within the interval. The closest markers to Pik-p were K28
      (approximately 0.60 centimorgans [cM]) and K39 (approximately 0.07 cM). A further
      four markers in the K28-K39 interval were developed from an in silico analysis
      based on the cv. Nipponbare genome sequence, and these all co-segregated with Pik
      p. This 0.67-cM region is equivalent to a physical separation in cv. Nipponbare
      of approximately 126 kb, plus an as-yet-unfilled genomic gap of unknown length.
      Four nucleotide-binding site leucine-rich repeat-type resistance genes are
      present in this interval, and these represent good candidates for Pik-p.

PMID- 19594310
TI  - Multilocus sequence typing reveals two evolutionary lineages of Acidovorax avenae
      subsp. citrulli.
AB  - Acidovorax avenae subsp. citrulli, causal agent of bacterial fruit blotch, has
      caused considerable damage to the watermelon and melon industry in China and the
      United States. Understanding the emergence and spread of this pathogen is
      important for controlling the disease. To build a fingerprinting database for
      reliable identification and tracking of strains of A. avenae subsp. citrulli, a
      multilocus sequence typing (MLST) scheme was developed using seven conserved
      loci. The study included 8 original strains from the 1978 description of A.
      avenae subsp. citrulli, 51 from China, and 34 from worldwide collections. Two
      major clonal complexes (CCs), CC1 and CC2, were identified within A. avenae
      subsp. citrulli; 48 strains typed as CC1 and 45 as CC2. All eight original 1978
      strains isolated from watermelon and melon grouped in CC1. CC2 strains were
      predominant in the worldwide collection and all but five were isolated from
      watermelon. In China, a major seed producer for melon and watermelon, the
      predominant strains were CC1 and were found nearly equally on melon and
      watermelon.

PMID- 19594311
TI  - Differentiation of eleven Fusarium spp. isolated from sugar beet, using
      restriction fragment analysis of a polymerase chain reaction-amplified
      translation elongation factor 1alpha gene fragment.
AB  - Sugar beet in Europe is commonly grown in wheat and maize crop rotations and
      subsequently pile-stored for several weeks. Beet is threatened by the
      colonization of saprophytic as well as pathogenic Fusarium spp. A tool for
      reliable identification based on sequence information of the translation
      elongation factor 1alpha (TEF-1alpha) gene was developed for the numerous
      Fusarium spp. being isolated from sugar beets. In all, 65 isolates from different
      species (Fusarium avenaceum, F. cerealis, F. culmorum, F. equiseti, F.
      graminearum, F. oxysporum, F. proliferatum, F. redolens, F. solani, F.
      tricinctum, and F. venenatum) were obtained from sugar beet at different
      developmental stages from locations worldwide. Database sequences for additional
      species (F. sporotrichioides, F. poae, F. torulosum, F. hostae, F. sambucinum, F.
      subglutinans, and F. verticillioides), isolated from sugar beets in previous
      studies, were included in the analysis. Molecular sequence analysis of the
      partial TEF-1alpha gene fragment revealed sufficient variability to differentiate
      between the Fusarium spp., resulting in species-dependent separation of the
      isolates analyzed. This interspecific divergence could be translated into a
      polymerase chain reaction restriction fragment length polymorphism assay using
      only two subsequent restriction digests for the differentiation of 17 of 18
      species.

PMID- 19594312
TI  - Analysis of nonlinear relationships in dual epidemics, and its application to the
      management of grapevine downy and powdery mildews.
AB  - Dual epidemics are defined as epidemics developing on two or several plant organs
      in the course of a cropping season. Agricultural pathosystems where such
      epidemics develop are often very important, because the harvestable part is one
      of the organs affected. These epidemics also are often difficult to manage,
      because the linkage between epidemiological components occurring on different
      organs is poorly understood, and because prediction of the risk toward the
      harvestable organs is difficult. In the case of downy mildew (DM) and powdery
      mildew (PM) of grapevine, nonlinear modeling and logistic regression indicated
      nonlinearity in the foliage-cluster relationships. Nonlinear modeling enabled the
      parameterization of a transmission coefficient that numerically links the two
      components, leaves and clusters, in DM and PM epidemics. Logistic regression
      analysis yielded a series of probabilistic models that enabled predicting preset
      levels of cluster infection risks based on DM and PM severities on the foliage at
      successive crop stages. The usefulness of this framework for tactical decision
      making for disease control is discussed.

PMID- 19594313
TI  - Triticum mosaic virus: a distinct member of the family potyviridae with an
      unusually long leader sequence.
AB  - The complete genome sequence of Triticum mosaic virus (TriMV), a member in the
      family Potyviridae, has been determined to be 10,266 nucleotides (nt) excluding
      the 3' polyadenylated tail. The genome encodes a large polyprotein of 3,112 amino
      acids with the "hall-mark proteins" of potyviruses, including a small overlapping
      gene, PIPO, in the P3 cistron. The genome of TriMV has an unusually long 5'
      nontranslated region of 739 nt with 12 translation initiation codons and three
      small open reading frames, which resemble those of the internal ribosome entry
      site containing 5' leader sequences of the members of Picornaviridae. Pairwise
      comparison of 10 putative mature proteins of TriMV with those of representative
      members of genera in the family Potyviridae revealed 33 to 44% amino acid
      identity within the highly conserved NIb protein sequence and 15 to 29% amino
      acid identity within the least conserved P1 protein, suggesting that TriMV is a
      distinct member in the family Potyviridae. In contrast, TriMV displayed 47 to 65%
      amino acid sequence identity with available sequences of mature proteins of
      Sugarcane streak mosaic virus (SCSMV), an unassigned member of the Potyviridae.
      Phylogenetic analyses of the complete polyprotein, NIa-Pro, NIb, and coat protein
      sequences of representative species of six genera and unassigned members of the
      family Potyviridae suggested that TriMV and SCSMV are sister taxa and share a
      most recent common ancestor with tritimoviruses or ipomoviruses. These results
      suggest that TriMV and SCSMV should be classified in a new genus, and we propose
      the genus Poacevirus in the family Potyviridae, with TriMV as the type member.

PMID- 19594314
TI  - Modeling infection of spring onion by Puccinia allii in response to temperature
      and leaf wetness.
AB  - The influence of temperature and leaf wetness duration on infection of spring
      onion (Japanese bunching onion) leaves by Puccinia allii was examined in
      controlled-environment experiments. Leaves of potted spring onion plants (Allium
      fistulosum cv. Yoshikura) were inoculated with urediniospores and exposed to 6.5,
      10, 15, 22, or 27 h of wetness at 5, 10, 15, 20, or 25 degrees C. The lesion that
      developed increased in density with increasing wetness duration. Relative
      infection was modeled as a function of both temperature and wetness duration
      using the modified version of Weibull's cumulative distribution function (R(2) =
      0.9369). Infection occurred between 6.5 and 27 h of leaf wetness duration at 10,
      15, 20, and 25 degrees C and between 10 and 27 h at 5 degrees C, and increased
      rapidly between 6.5 and 15 h of wetness at 10, 15, and 20 degrees C. At 25
      degrees C, few uredinia developed regardless of the wetness duration. Parameter
      H, one of eight parameters used in the equation and which controls the asymmetry
      in the response curve, varied markedly according to the temperature, so that the
      model could be improved by representing H as a function of wetness duration (R(2)
      = 0.9501).

PMID- 19594315
TI  - Association of soil chemical and physical properties with Pythium species
      diversity, community composition, and disease incidence.
AB  - A high-throughput baiting and identification process identified more than 7,000
      isolates of Pythium from 88 locations in Ohio. Isolates were identified using
      direct-colony polymerase chain reaction followed by single-strand conformational
      polymorphism, and communities were assembled using the Jaccard similarity
      coefficient and cluster analysis. Both univariate and multivariate statistics
      were used to evaluate differences in soil properties between communities, and
      canonical discriminant analysis (CDA) was used to assess the strength of the
      association of soil variables within communities from 83 of the locations. In
      all, 21 species of Pythium were identified but only 6 were recovered from >40% of
      the locations. Five communities were formed using the cluster analysis, and
      significant differences were observed in disease incidence, as well as soil pH,
      calcium, magnesium, and cation exchange capacity between communities. Stepwise
      multiple discriminant analysis and CDA identified pH, calcium, magnesium, and
      field capacity as contributing the most to the separation of the five Pythium
      communities. There was a strong association between abiotic soil components and
      the structure of Pythium communities, as well as diversity of Pythium spp.
      collected from agronomic production fields in Ohio.

PMID- 19594316
TI  - Characterization of genetic components involved in durable resistance to stripe
      rust in the bread wheat 'Renan'.
AB  - Stripe rust, caused by Puccinia striiformis f. tritici, is one of the most
      widespread and destructive wheat diseases in areas where cool temperatures
      prevail. The wheat cv. Renan, carrying the specific gene Yr17, has shown
      effective resistance for a long time, even though some pathotypes overcame the
      Yr17 gene. The objectives of this study were to locate and map genetic loci
      associated with adult-plant resistance (APR) to stripe rust in a recombinant
      inbred line population derived from a cross between Renan (resistant) and Recital
      (susceptible). Field assays were performed for 4 years (1995, 1996, 2005, and
      2006) to score disease-progress data and identify APR quantitative trait loci
      (QTLs). Three QTLs, QYr.inra-2BS, QYr.inra-3BS, and QYr.inra-6B, with resistance
      alleles derived from Renan were detected in 1995 to 1996 with the 237E141
      pathotype, which is avirulent against genotypes carrying Yr17. These QTLs were
      stable and explained a major part of the phenotypic variation seen in 2005 to
      2006, when the 237E141 V17 pathotype was used. Each of these QTLs contributed
      approximately 4 to 15% of the phenotypic variance and was effective at different
      adult plant stages. Interactions were observed between some markers of the Yr17
      gene and three Renan QTLs: QYr.inra-2BS, QYr.inra-3BS, and QYr.inra-6B.
      Resistance based on the combination of different APR types should provide durable
      resistance to P. striiformis.

PMID- 19594317
TI  - Geostatistical analysis of the spatiotemporal dynamics of powdery mildew and leaf
      rust in wheat.
AB  - Plant diseases are dynamic systems that progress or regress in spatial and
      temporal dimensions. Site-specific or temporally optimized disease control
      requires profound knowledge about the development of each stressor. The
      spatiotemporal dynamics of leaf rust (Puccinia recondite f. sp. tritici) and
      powdery mildew (Blumeria graminis f. sp. tritici) in wheat was analyzed in order
      to evaluate typical species-dependent characteristics of disease spread. During
      two growing seasons, severity data and other relevant plant growth parameters
      were collected in wheat fields. Spatial characteristics of both diseases were
      assessed by cluster analyses using spatial analysis by distance indices, whereas
      the temporal epidemic trends were assessed using statistical parameters.
      Multivariate statistics were used to identify parameters suitable for
      characterizing disease trends into four classes of temporal dynamics. The results
      of the spatial analysis showed that both diseases generally occurred in patches
      but a differentiation between the diseases by their spatial patterns and spread
      was not possible. In contrast, temporal characteristics allowed for a
      differentiation of the diseases, due to the fact that a typical trend was found
      for leaf rust which differed from the trend of powdery mildew. Therefore, these
      trends suggested a high potential for temporally optimized disease control.
      Precise powdery mildew control would be more complicated due to the observed high
      variability in spatial and temporal dynamics. The general results suggest that,
      in spite of the high variability in spatiotemporal dynamics, disease control that
      is optimized in space and time is generally possible but requires consideration
      of disease- and case-dependent characteristics.

PMID- 19594318
TI  - Morphological, genetic, and pathogenic characterization of Colletotrichum
      acutatum, the cause of anthracnose of almond in Australia.
AB  - Almond anthracnose was reported for the first time in Australia in 1998 and has
      since been observed in all of the major almond-growing regions. The organism
      causing anthracnose was confirmed as Colletotrichum acutatum using taxon-specific
      polymerase chain reaction (PCR). Three main morphotypes of C. acutatum from
      almond in Australia were identified (namely, pink, orange, and cream colony
      color) and the optimum temperature for mycelial growth of representative isolates
      was 25 degrees C. Australian isolates of C. acutatum were more similar
      morphologically to the pink subpopulation of C. acutatum from California than to
      the gray Californian subpopulation and the isolates of Colletotrichum from
      Israel. Inter-simple-sequence-repeat (ISSR) PCR analysis revealed that the
      majority of Australian isolates shared an identical banding pattern whereas
      Australian isolates of C. acutatum from almond were distinct from isolates of the
      pink and gray subpopulations of C. acutatum from almond in California and of
      Colletotrichum spp. from almond in Israel. Sequence analysis of the internally
      transcribed spacer (ITS1-2) ribosomal DNA region of representative isolates
      differed from the results of ISSR-PCR in that polymorphisms were revealed among
      isolates, indicating that some genetic variation may be present. Pathogenicity
      experiments on detached leaves and fruit revealed pathogenic variation among
      representative isolates of C. acutatum from almond in Australia, California, and
      Israel; however, all isolates tested caused disease. Distinct subgroups among
      Australian isolates of C. acutatum from almond were not supported on the basis of
      morphology, mycelial growth rates, ISSR-PCR, and pathogenicity.

PMID- 19594319
TI  - Xanthomonas axonopodis pv. glycines soybean cultivar virulence specificity is
      determined by avrBs3 homolog avrXg1.
AB  - Three races of Xanthomonas axonopodis pv. glycines were identified on pustule
      disease resistant and susceptible soybean cultivars based on virulence phenotype.
      For race 3, an avrBs3 homolog, avrXg1 was identified that conferred resistance
      expressed as a hypersensitive response on resistant cultivar Williams 82.
      Mutations in two predicted functional domains of avrXg1 resulted in gained
      virulence on Williams 82 and an increase in bacterial population number on
      susceptible cultivars. Expression of avrXg1 in race 1, that is predicted to
      confer a nonspecific HR, led to virulence on susceptible cultivars Spencer and PI
      520733. Expression of avrXg1 in race 2, that is predicted of carrying avrBs3-like
      genes, resulted in gained virulence and fitness of pathogen on both resistant and
      susceptible cultivars. The results demonstrate multifunctions for avrXg1
      dependent on pathogen and plant genetic backgrounds.

PMID- 19594320
TI  - Changing structure of the femoral neck across the adult female lifespan.
AB  - The anatomic distribution of cortical and cancellous bone in the femoral neck may
      be critical in determining resistance to fracture. We investigated the effects of
      aging on femoral neck bone in women. In this cross-sectional study, we used
      clinical multidetector computed tomography (MDCT) of the hips to investigate
      aging effects in 100 female volunteers aged 20 to 90 years. We developed a
      clinically efficient protocol to measure cortical thickness (C.Th) and cortical,
      trabecular, and integral bone mineral density (CtBMD, TrBMD, and iBMD in
      mg/cm(3)) in anatomic quadrants of the femoral neck. We used a nested ANOVA to
      evaluate their associations with height, weight, location in the femoral neck,
      and age of the subject. Age was the principal determinant of both cortical
      thickness and BMD. Age had significantly different effects within the anatomic
      quadrants; compared with young women, elderly subjects had relative preservation
      of the inferoanterior (IA) quadrant but strikingly reduced C.Th and BMD
      superiorly. A model including height, weight, and region of interest (and their
      interactions) explained 83% of the measurement variance (p < .0001). There were
      marked C.Th and BMD differences between age 25 and age 85 in the already thin
      superior quadrants. At 25 years the predicted C.Th of the superoposterior
      quadrant was 1.63 mm, whereas at 85 years it was 0.33 mm [-1.33 mm, 95%
      confidence interval (CI) of difference over 60 years -1.69 to -0.95]. By
      contrast, at 25 years mean C.Th of the IA quadrant was 3.9 mm, whereas at 85
      years it was 3.3 mm (-0.6 mm, 95% CI -0.83 to -0.10). CtBMD of the IA region was
      equivalent at 25 and 85 years. In conclusion, elderly women had relative
      preservation of IA femoral neck bone over seven decades compared with young women
      but markedly lower C.Th and BMD in the other three quadrants. The IA quadrant
      transmits mechanical load from walking. Mechanical theory and laboratory tests on
      cadaveric femurs suggest that localized bone loss may increase the risk of
      fracture in elderly fallers. It remains to be determined whether this MDCT
      technique can provide better prediction of hip fracture than conventional
      clinical dual X-ray absorptiometry (DXA).

PMID- 19594321
TI  - Coronary calcification is associated with lower bone formation rate in CKD
      patients not yet in dialysis treatment.
AB  - Vascular calcification is a strong prognostic marker of mortality in hemodialysis
      patients and has been associated with bone metabolism disorders in this
      population. In earlier stages of chronic kidney disease (CKD), vascular
      calcification also has been documented. This study evaluated the association
      between coronary artery calcification (CAC) and bone histomorphometric parameters
      in CKD predialysis patients assessed by multislice coronary tomography and by
      undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their
      median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic
      alterations observed included low trabecular bone volume, increased eroded and
      osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic
      regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was
      independently associated with the presence of coronary calcification [p = .009;
      odd ratio (OR) = 0.15; 95% confidence interval (CI) 0.036-0.619]. This study
      showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also,
      there was an independent association of low bone formation and CAC in this
      population. In conclusion, our results provide evidence that low bone-formation
      rate constitutes another nontraditional risk factor for cardiovascular disease in
      CKD patients.

PMID- 19594322
TI  - Protein phosphatase magnesium-dependent 1A-mediated inhibition of BMP signaling
      is independent of Smad dephosphorylation.
AB  - Phosphorylation of Smad1/5/8 at carboxyl-terminal serine residues by type I
      receptors activates downstream bone morphogenetic protein (BMP) signaling.
      Protein phosphatase magnesium-dependent 1A (PPM1A) has been shown to suppress BMP
      activity by dephosphorylating phospho-Smads. We report here that PPM1A suppresses
      BMP signaling via a novel mechanism. PPM1A inhibited a constitutively activated
      Smad1 mutant lacking BMP receptor phosphorylation sites. PPM1A reduced the
      protein levels not only of Smad1 but also of Smad5 and Smad8. A proteasome
      inhibitor blocked the inhibitory effects of PPM1A on Smad1, but the Smurf-binding
      motif in the Smad1 linker region was not involved in this inhibition. The
      phosphatase activity of PPM1A is essential for inhibition. Taken together, these
      findings suggest that through the dephosphorylation of unidentified substrate(s),
      PPM1A inhibits BMP signaling by decreasing Smad protein levels via the proteasome
      pathway. Moreover, knockdown of endogenous PPM1A stimulated osteoblastic
      differentiation, suggesting that PPM1A may physiologically suppress BMP signaling
      via Smads.

PMID- 19594323
TI  - Impact of neutropenic complications on short-term disability in patients with
      cancer receiving chemotherapy.
AB  - OBJECTIVES: The study examined the impact of chemotherapy-induced neutropenic
      complications (CINC), defined as neutropenia with fever or infection, on short
      term disability (STD) among cancer patients receiving chemotherapy. METHODS: The
      key outcome metrics were average monthly STD days and associated indirect costs.
      Patients with and without CINC were propensity score (PS) matched. Multivariate
      regressions were conducted on PS-matched cohorts to estimate the marginal impact
      of CINC. RESULTS: A total of 280 patients with CINC were PS-matched to 280
      patients without CINC. Compared with matched patients, patients with CINC on
      average experienced 0.9 more STD day (3.2 vs. 2.3, p=0.046) and $155 more in
      indirect costs ($549 vs. 394, p=0.050) per month. After multivariate adjustment,
      patients with CINC experienced 1.0 more STD day (p=0.029), and incurred $200 more
      in indirect cost (p=0.016) per month. CONCLUSIONS: Patients with CINC experience
      significantly greater STD leave than patients with no neutropenic complications
      from cancer chemotherapy. The overall study sample only included patients from
      large self-insured employers in the US and may not reflect the work loss
      experience of all employed patients in the US or other countries. Indirect costs
      associated with absenteeism and presenteeism were not measured.

PMID- 19594324
TI  - Why are so many people so unashamedly selfish about the prospect of combating
      aging?

PMID- 19594325
TI  - Weight loss in obese men is associated with increased telomere length and
      decreased abasic sites in rectal mucosa.
AB  - Telomere shortening may cause genome instability and is an initiating event in
      colorectal cancer (CRC). Obesity is associated with reduced telomere length in
      lymphocytes and is a risk factor for CRC, but the impact of obesity on telomere
      length in the rectal mucosa is unknown. The purpose of this study was to
      investigate the effect of weight loss, induced by calorie-restricted diets, on
      telomere length in the rectal mucosa of obese men. Midrectal biopsies were
      collected by sigmoidoscopy at three time points (at weeks 0, 12, and 52) during a
      programmed weight loss intervention. Weight was reduced by an average of 10.6 kg
      across the study. Telomere length, measured by quantitative real-time PCR (qPCR),
      was negatively correlated with body mass index (BMI) (r = -0.13, p = 0.05) at
      baseline (n = 54) and increased at week 12 (four-fold increase) and week 52 (10
      fold increase) (analysis of covariance [ANCOVA] p = 0.01, n = 12). Abasic sites
      in DNA decreased at week 12 (30% decrease) and week 52 (65% decrease) (analysis
      of variance [ANOVA] p = 0.02). Furthermore, gain of telomere length appeared to
      be greater if more weight and body fat was lost (r = -0.65, p = 0.01 and r = 
      0.56, p = 0.01, respectively). These results suggest that weight loss by caloric
      restricted diets may contribute to the prevention of telomere shortening and DNA
      base damage, which are important initiating events in carcinogenesis.

PMID- 19594326
TI  - Characteristics of 400-meter walk test performance and subsequent mortality in
      older adults.
AB  - The purpose was to examine the relationship between performance in the 400-meter
      walking test and mortality. Data are from a population-based sample of 948
      Italian men and women > or =65 years. The main outcome measures that were
      assessed comprised time to complete the 400-meter walk, 20-meter lap time
      coefficient of variation, need to rest during the test, and ability to complete
      the walk. All-cause mortality was ascertained over a 6-year follow-up period.
      Data were analyzed with proportional hazard logistic and linear regression
      analyses. In age- and sex-adjusted analyses, all 400-meter walking test variables
      except need to rest were associated with mortality. After further adjusting for
      the Mini-Mental State Examination, symptoms of depression, education, smoking,
      body mass index, being sedentary/minimally active, disease burden, and lower
      extremity performance (Short Physical Performance Battery score), both time to
      complete the 400-meter walk and lap time coefficient of variation were
      significant independent predictors of mortality. We conclude that multiple
      aspects of performance in the 400-meter walk test provide complementary
      information on mortality prognosis in older persons.

PMID- 19594327
TI  - The expression of CYP2D22, an ortholog of human CYP2D6, in mouse striatum and its
      modulation in 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's
      disease phenotype and nicotine-mediated neuroprotection.
AB  - The main contributory factors of Parkinson's disease (PD) are aging, genetic
      factors, and environmental exposure to pesticides and heavy metals. CYP2D22, a
      mouse ortholog of human CYP2D6, is expected to participate in a chemically
      induced PD phenotype due to its structural resemblance with CYP2D6. Despite its
      expected participation in PD, its expression in the nigrostriatal tissues and
      modulation by the chemicals that induce PD or offer neuroprotection have not yet
      been investigated. The present study was undertaken to investigate CYP2D22
      expression in mouse striatum and to assess its involvement in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD phenotype and nicotine
      mediated neuroprotection. The animals were treated intraperitoneally daily with
      nicotine (1 mg/kg) for 8 weeks, followed by MPTP (20 mg/kg) + nicotine (1 mg/kg)
      for 2-4 weeks and vice versa, along with respective controls. In some sets of
      experiments, the animals were treated with ketoconazole (300 mg/kg), a
      CYP3AH/CYP2D22 inhibitor, along with nicotine and/or MPTP. Tyrosine hydroxylase
      (TH)-immunoreactivity in the substantia nigra, the expression of nicotinic
      acetylcholine receptors (nAChRs) alpha6 and alpha4, dopamine content, and 1
      methyl-4-phenylpyridinium ion (MPP(+)) level in the striatum were measured to
      confirm the MPTP-induced PD phenotype and nicotine-mediated neuroprotection.
      CYP2D22 and nAChRs expressions were measured in the striatum by RT-PCR/western
      blotting and dopamine level; CYP2D22 catalytic activity and MPP(+) content were
      determined by high-performance liquid chromatography (HPLC). MPTP increased
      dopaminergic neuronal degeneration and the striatal MPP(+) level and reduced
      striatal dopamine content; it attenuated expression/activity of CYP2D22 and
      nAChRs that were significantly restored in nicotine-treated animals. Ketoconazole
      reduced the nicotine-mediated increase in CYP2D22 expression and activity,
      dopamine content, and TH-immunoreactivity. The results indicate the expression of
      CYP2D22 in mouse striatum and its possible role in the MPTP-induced PD phenotype
      and nicotine-mediated neuroprotection.

PMID- 19594328
TI  - Nuclear DNA damage as a direct cause of aging.
AB  - This paper presents evidence that damage to nuclear DNA (nDNA) is a direct cause
      of aging in addition to the effects of nDNA damage on cancer, apoptosis, and
      cellular senescence. Many studies show significant nDNA damage with age,
      associated with declining nDNA repair, and this evidence for the decline of nDNA
      repair with age is also reviewed. Mammalian lifespans correlate with the
      effectiveness of nDNA repair. The most severe forms of accelerated aging disease
      in humans are due to nDNA repair defects, and many of these diseases do not
      exhibit increased cancer incidence. High rates of cellular senescence and
      apoptosis due to high rates of nDNA damage are apparently the main cause of the
      elderly phenotype in these diseases. Transgenic mice with high rates of cellular
      senescence and apoptosis exhibit an elderly phenotype, whereas some strains with
      low rates of cellular senescence and apoptosis show extended lifespan. Age
      associated increases of nDNA damage in the brain may be problematic for
      rejuvenation because neurons may be difficult to replace and artificial nDNA
      repair could be difficult.

PMID- 19594329
TI  - Age-dependent down-regulation of mitochondrial 8-oxoguanine DNA glycosylase in
      SAM-P/8 mouse brain and its effect on brain aging.
AB  - Mitochondrial DNA (mtDNA) damage has been hypothesized to be responsible for
      aging and various neurological diseases. Abnormalities in 8-oxoguanine DNA
      glycosylase (OGG1) function can promote DNA oxidative damage, especially in the
      mitochondria. Here we report changes in the expression of OGG1 targeting to the
      nucleus, cytosol, and mitochondria in both accelerated senescence mice (SAM-P/8)
      and normal counterpart SAM-R/1 mice during brain aging. Our results showed that
      mRNA and protein levels of OGG1, especially OGG1 targeting to mitochondria, and
      the expression level of cytochrome c oxidase subunit III (COX III) in the brain
      of both SAM-P/8 mice and SAM-R/1 mice, decreased with age. However, such an age
      dependent decrease in SAM-P/8 mice was larger than that in normal SAM-R/1 mice.
      These findings support the concept that down-regulation of OGG1, especially
      mitochondrial OGG1(mtOGG1) in SAM-P/8 mice, may promote brain aging by its effect
      on imbalance in the mtDNA damage repair systems, which leads to accumulation of
      mtDNA damage and oxidative phosphorylation-related protein dysfunction. Overall,
      our results provide novel insight into underlying the molecular mechanisms during
      brain aging.

PMID- 19594330
TI  - How is mutant mitochondrial DNA clonally amplified? Much new evidence, still no
      answers.
AB  - Twenty years have passed since Kadenbach and Muller-Hocker first proposed that
      the age-related accumulation of mutant mitochondrial DNA is caused by its clonal
      expansion, rather than by a "vicious cycle" of de novo mutational events caused
      by the disruptive metabolic impact of prior ones. Proof that they were correct
      emerged rapidly (though recognition of this was much slower); however, the
      mechanism underlying this selective advantage remained obscure. Numerous
      hypotheses were advanced during the 1990s, but proved hard to test. A wealth of
      data has been published very recently that bears on this question. While these
      reports surely bring us closer to an understanding of this phenomenon, and thus
      probably to a better understanding of how it might be combated or even reversed,
      they currently raise more questions than they answer.

PMID- 19594332
TI  - Interview with Nigel M. de S. Cameron, ph.d. Interviewed by Vicki Glaser.

PMID- 19594333
TI  - Living and all-time world longevity record-holders over the age of 110.

PMID- 19594337
TI  - With age ... Confidence?

PMID- 19594338
TI  - State of Washington, third state to permit aid in dying.

PMID- 19594340
TI  - Regarding Kathryn Tucker's "ensuring informed end-of-life decisions".

PMID- 19594341
TI  - The relationship between palliative care and legalized euthanasia in Belgium.

PMID- 19594342
TI  - Palliative care seeks its home in national health care reform.

PMID- 19594343
TI  - Extending computer technology to hospice research: interactive pentablet
      measurement of symptoms by hospice cancer patients in their homes.
AB  - We aimed to determine the acceptability and feasibility of a pentablet-based
      software program, PAINReportIt-Plus, as a means for patients with cancer in home
      hospice to report their symptoms and differences in acceptability by demographic
      variables. Of the 131 participants (mean age = 59 +/- 13, 58% women, 48.1%
      African American), 44% had never used a computer, but all participants easily
      used the computerized tool and reported an average computer acceptability score
      of 10.3 +/- 1.8, indicating high acceptability. Participants required an average
      of 19.1 +/- 9.5 minutes to complete the pain section, 9.8 +/- 6.5 minutes for the
      medication section, and 4.8 +/- 2.3 minutes for the symptom section. The
      acceptability scores were not statistically different by demographic variables
      but time to complete the tool differed by racial/ethnic groups. Our findings
      demonstrate that terminally ill patients with cancer are willing and able to
      utilize computer pentablet technology to record and describe their pain and other
      symptoms. Visibility of pain and distress is the first step necessary for the
      hospice team to develop a care plan for improving control of noxious symptoms.

PMID- 19594344
TI  - Teaching dying patient care in three universities in Argentina, Spain, and Italy.
AB  - We performed a multicenter comparative survey on undergraduate medical education
      regarding the care of dying patients at medical schools in three countries. We
      enrolled 380 first- and sixth-year medical students from Universidad Austral
      (Argentina), Universidad de Navarra (Spain), and Universita Campus Biomedico di
      Roma (Italy). Answers to the questions were similar among the three universities.
      Students acknowledged interacting directly with dying patients in all cases.
      Attitudes toward dying patients were highly positive. Students spontaneously
      requested more training in end-of-life care. Some attitudes and wishes varied
      significantly from course to course. Students perceived that this issue received
      more attention in humanistic rather than in clinical subjects. Ninety-eight
      percent of students considered that death and helping patients to have a good
      death should be included in their training. Students' attitudes revealed high
      interest and poor training in end-of-life issues. Medical curricula should be
      improved to adequately address these issues.

PMID- 19594345
TI  - A model to improve value: the interdisciplinary palliative care services
      agreement.
AB  - Abstract This article examines the definition of value in medical care for
      palliative care patients and describes an Interdisciplinary Palliative Care
      Services Agreement, which is a framework for valued, financially sustainable
      palliative care at a 500-bed academic medical center. Quality standards drive
      team interventions and also serve as metrics for financial support. The agreement
      defines staffing ratios necessary for sustainable team growth and represents a
      financial model that positions the field of palliative medicine competitively
      among other medical specialities.

PMID- 19594346
TI  - Building competence in pediatric end-of-life care.
AB  - BACKGROUND: Pediatric end-of-life care involves multiple decision-makers
      including the patient, the family, and the health care provider. Although some
      information exists on the role of patient and family values on decision making,
      little is known about what influences the health care provider's decisions and
      performance. OBJECTIVE: A survey was conducted to collect data on health care
      providers who provide pediatric end-of-life care to determine what factors
      influence provider confidence in managing eleven different end-of-life care
      issues. DESIGN: An electronic 34-question survey was circulated in 2005 at a
      single children's hospital in Western Michigan. RESULTS: One hundred fifty-seven
      responses were received. Age had the highest association with confidence. Older
      responders reported more confidence than their younger colleagues (odds ratio
      [OR] 3.3-26.1 on eight issues). Other provider factors associated with higher
      confidence levels included male gender (OR 3.6-11.2 on five issues), experience
      (OR 2.7-4.6 on five issues) and not being religious (OR 3.1-3.4 on three issues).
      Responders who received formal education during training felt better prepared
      than those who did not (17.1% versus 3.8% felt at least well prepared,
      respectively). CONCLUSIONS: Age and experience create confidence in managing
      pediatric end-of-life care issues. Other provider variables including gender and
      religious beliefs may also influence confidence on some issues. Although formal
      education helps providers feel better prepared to care for children with terminal
      conditions, the majority of providers still feel no more than adequately prepared
      by their training. More emphasis on experience-driven education delivered by
      seasoned educators may improve confidence in delivering pediatric end-of-life
      care.

PMID- 19594348
TI  - Introduction to hierarchical modeling.
AB  - BACKGROUND: Hierarchical modeling (HM) is a statistical technique that has gained
      in popularity in health care research. It has been used for analysis of secondary
      data, performance profiles or benchmarking studies, and in prospective trials.
      The technique is used in situations in which traditional regression analysis
      might lead to incorrect conclusions. Specifically, data drawn from nested
      settings such as hospital units or hospice providers may be correlated, thus
      violating an assumption required for ordinary least squares regression.
      OBJECTIVE: This article provides a description of HM, reviews two recent articles
      in palliative care that have used the technique, and presents an illustrative
      case study to further illuminate the potential of the method. CONCLUSION: When
      used appropriately, HM allows researchers to specify and test hypotheses that
      would not otherwise be possible, and avoid incorrect conclusions from nested
      data.

PMID- 19594347
TI  - Racial/ethnic patterns of care for pancreatic cancer.
AB  - INTRODUCTION: The small proportion of cancers diagnosed at the local disease
      stage, resectable at the time diagnosis, and responsive to chemotherapy
      contribute to poor survival making pancreatic cancer the fourth leading cause of
      cancer death among Americans. This emphasizes the importance of receiving
      appropriate palliative care. Racial/ethnic cancer treatment disparities have been
      observed for many cancer sites. We examine patterns of care in a population-based
      sample of African American, Hispanic and non-Hispanic white patients diagnosed
      with pancreatic cancer. METHODS: Eligible cases were age 20 or older and newly
      diagnosed in 1998 with primary adenocarcinoma of the pancreas reported to the
      National Cancer Institute's Surveillance Epidemiology and End Results (SEER)
      program and selected for the NCI Patterns of Care/Quality of Care (POC/QOC)
      project (n = 697). RESULTS: Chemotherapy, the most frequently received treatment
      was less frequently received by African American patients (odds ratio [OR] 0.61,
      95% confidence interval [CI] 0.37-0.95) and radiation less frequently received by
      Hispanic compared to non-Hispanic white white patients (OR 0.50, 95% CI, 0.27
      0.95) after adjustment for age, stage, size of tumor, and insurance status in a
      multivariate regression model. Cancer-directed surgery of the primary site was
      received by 14.1% of patients, which did not significantly differ by
      race/ethnicity. Uninsured patients less often were recommended for or received
      surgery (OR 0.09, 95% CI 0.01-0.62) and (OR 0.07, 95% CI, 0.01-0.49),
      respectively. CONCLUSION: Differences in primary tumor size, stage and insurance
      status contributed to racial/ethnic differences in the receipt of cancer-directed
      surgery but did not explain differences in the receipt of chemotherapy for
      African American or radiation for Hispanic patients. More population-based
      research is needed to examine race/ethnicity, insurance status and receipt of
      treatment and palliative care for pancreatic cancer.

PMID- 19594349
TI  - Health professional burnout: part I #167.

PMID- 19594350
TI  - Health professional burnout: part I #167.

PMID- 19594351
TI  - Life did not stop at the doors to the palliative care ward.

PMID- 19594352
TI  - Fossil docs.

PMID- 19594354
TI  - Treatment of painful bone metastases in hormone-refractory prostate cancer with
      zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid
      combined.
AB  - Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated
      in patients with cancer with painful osseous metastases to palliate pain symptoms
      or to prevent skeletal-related events. Both pharmaceuticals may have an additive
      or even synergistic palliative effect. The combined use of bone-seeking
      radiopharmaceuticals and bisphosphonates is, however, controversial because of
      assumed competition between both phosphonate-compounds at the bone level. We
      report a case of hormone-refractory prostate cancer (HRPC) with multiple painful
      osseous metastases. The patient was treated with samarium-153
      ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio
      International, Saclay, France) in combination with zoledronic acid (Zometa,
      Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly
      intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm
      EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He
      experienced a total relief of pain, a significant decrease of prostate-specific
      antigen (PSA) and, surprisingly, a significant decrease of tumor burden.

PMID- 19594358
TI  - JPM patient information. Seizures at the end of life.

PMID- 19594360
TI  - Osteoclast differentiation induced by synthetic octacalcium phosphate through
      receptor activator of NF-kappaB ligand expression in osteoblasts.
AB  - Synthetic octacalcium phosphate (OCP) has a potential to enhance new bone
      formation and exhibits biodegradable characteristics when implanted in
      experimentally created bone defects. The precise mechanisms of OCP biodegradation
      remain unclear, though histological observations have revealed that bone
      resorbing osteoclasts appear and resorb implanted OCP. To investigate how
      osteoclasts develop around implanted OCP, we examined osteoclast differentiation
      using OCP crystals in vitro. Coculturing of mouse bone marrow cells and
      osteoblasts in OCP-coated cell culture plates induced osteoclast differentiation,
      whereas that did not occur without coating. Further, addition of bone
      morphogenetic protein-2 significantly increased the number of osteoclasts in the
      OCP-coated wells. In the presence of OCP, osteoblasts expressed receptor
      activator of NF-kappaB ligand (RANKL), an osteoclast differentiation factor. In
      addition, when half of each culture well was coated with OCP, osteoclasts were
      formed in both coated and noncoated areas, suggesting that soluble factors
      mediate osteoclast differentiation induced by OCP. Also, calcium levels in
      culture medium were significantly decreased in the presence of OCP, while
      experimental reduction of calcium from 8.0 to 5.0 mg/dL significantly induced
      RANKL mRNA expression. These results suggest that OCP itself decreases calcium
      levels around implanted OCP, which induces osteoclast differentiation through
      RANKL expression by osteoblasts.

PMID- 19594361
TI  - Effective adenovirus-mediated gene transfer into neural stem cells derived from
      human embryonic stem cells.
AB  - Human embryonic stem cell-derived neural stem cells (hESC-NSCs) are an attractive
      cell type for studying aspects of brain development and pathology. To develop the
      full potential of this model system, it is important to establish a reliable
      methodology for the manipulation of gene expression in hNSCs. To address this
      issue, we used an adenoviral vector with a CMV promoter-driven green fluorescent
      protein (GFP) reporter gene (Ad5-GFP). We optimized conditions for Ad5-GFP
      infection and assessed the efficiency of infection of whole and dissociated
      embryonic stem cell (ESC)-derived neurospheres as well as the effect of
      adenoviral vectors on cell surface marker expression, proliferation, and
      differentiation potential. Our results demonstrate that most neurosphere cells (
      approximately 70%) express the coxsackie and adenovirus receptor and can be
      infected with Ad5. More specifically, the CD133+ hESC-NSC population could be
      infected more efficiently than the CD133 population and both populations
      expressed GFP at high levels. At low multiplicity of infection (MOI < 25), the
      virus had no significant effect on stem cell marker expression (CD133 and
      Nestin), cell survival, cell proliferation rate, or differentiation potential.
      This model system provides a practical new approach to study human NSC function
      in the context of neurodegenerative and neoplastic disorders.

PMID- 19594362
TI  - Skeletal myogenic potential of mouse skin-derived precursors.
AB  - Cell transplantation-based therapy could be an effective way for the treatment of
      many diseases. Among numerous somatic stem cells isolated and purified, skin
      derived precursors (SKPs) are abundant autologous cells, providing a large
      reservoir of cells for therapeutic transplantation. Previous studies showed that
      SKPs could be differentiated into neural and mesodermal progeny in vitro. In the
      present study, we attempted to differentiate SKPs to muscle progenitors in vitro.
      After treatment with a combination of growth factors, SKPs were differentiated
      into cells expressing markers of muscle progenitors, including Pax7. Furthermore,
      some of these cells expressed desmin, TnT, Mstn, and Myog, suggesting their
      differentiation into the muscular lineage. After single point injection, the
      differentiation of SKPs from green fluorescent protein positive donors into
      muscle precursors was also demonstrated in vivo. Additionally, donor SKPs
      migrated to the niche of muscle progenitors, participated in the regeneration of
      recipient muscles, and expressed markers of muscle progenitors, including Pax7, M
      cadherin, and MyoD. After recovery of donor cells from recipient muscles at 3
      weeks postinjection, some of the injected SKPs were converted to myogenic
      precursors, based on the expression of specific markers (Pax7 and MyoD). Some of
      these donor cells also expressed muscle makers (desmin, TnT, and Myog). At 20
      weeks postinjection, the injected SKPs were localized to recipient muscles
      without decreases in their population size. In summary, these findings indicated
      that SKPs could develop into muscle progenitors and differentiated muscle cells
      in vitro and in vivo, thus providing valuable autologous cells for the treatment
      of muscle diseases.

PMID- 19594363
TI  - MICA gene polymorphism not associated with nonsyndromic cleft lip with or without
      cleft palate in the Japanese population?
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most
      common birth defects. Despite its frequency, the etiology remains largely
      unknown. Most likely, both genetic and environmental factors contribute to this
      malformation. A polymorphic gene family, the major histocompatibility complex
      class I chain-related gene A (MICA), is located about 40 kb centromeric to the
      HLA-B gene. In this study, we analyzed the association between MICA gene
      polymorphisms and NSCLP in Japanese patients. METHODS: The (GCT)n polymorphism of
      the MICA gene was investigated in 94 patients with NSCLP and 180 normal controls
      using polymerase chain reaction amplification and denaturing polyacrylamide gel
      electrophoresis. RESULTS: Our results demonstrate that there are no differences
      in microsatellite allele frequency between NSCLP patients and controls. However,
      the microsatellite allele frequency of the MICA-A6 (p = 0.045) allele was
      increased in male patients, as compared with controls. Further, the MICA-A5 (p =
      0.359) allele was also increased in female NSCLP patients. CONCLUSION: These
      results suggest that the microsatellite allele frequencies of the MICA-A6 allele
      increased in male NSCLP patients. Although the MICA-A5 allele increased in female
      NSCLP patients, the increase was not statistically significant. These results
      suggest that the MICA gene could be one of the candidate genes for NSCLP.

PMID- 19594364
TI  - Gene-gene interactions among genetic variants from obesity candidate genes for
      nonobese and obese populations in type 2 diabetes.
AB  - Recent studies indicate that obesity may play a key role in modulating genetic
      predispositions to type 2 diabetes (T2D). This study examines the main effects of
      both single-locus and multilocus interactions among genetic variants in Taiwanese
      obese and nonobese individuals to test the hypothesis that obesity-related genes
      may contribute to the etiology of T2D independently and/or through such complex
      interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity
      candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3
      receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine
      nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor,
      proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1,
      uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed
      with T2D and 186 age- and sex-matched controls. Single-locus analyses showed
      significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the
      nonobese group (p = 0.002 and 0.047, respectively). Further, interactions
      involving GNB3 and PCSK1 were suggested among the nonobese population using the
      generalized multifactor dimensionality reduction method (p = 0.001). In addition,
      interactions among angiotensinogen, fat mass and obesity associated gene, GNB3,
      and uncoupling protein 3 genes were found in a significant four-locus generalized
      multifactor dimensionality reduction model among the obese population (p =
      0.001). The results suggest that the single nucleotide polymorphisms from the
      obesity candidate genes may contribute to the risk of T2D independently and/or in
      an interactive manner according to the presence or absence of obesity.

PMID- 19594365
TI  - G6PD Mediterranean S188F codon mutation is common among Saudi sickle cell
      patients and increases the risk of stroke.
AB  - AIM: To describe the molecular spectrum of G6PD gene mutation(s) in a population
      sample of Saudi Arabian Hemoglobin S (HBS) patients versus normal control from
      matching ethnicity. Additionally, we aim to investigate whether HBS patients with
      G6PD mutation(s) are at higher risk of developing a stroke. METHODS: DNA was
      extracted from 48 HBS patients and 42 controls. The HBS gene was fully screened
      for mutations by direct sequencing. HBS status was determined by the presence of
      the GAT to GTG codon mutation. Risk of stroke status was determined by abnormally
      high cerebral velocities by transcranial Doppler. Time averaged means of maximum
      velocities higher than 2 m/s (middle, internal carotid, or anterior cerebral
      arteries) were considered as abnormal. RESULTS: Screening the full G6PD gene
      revealed the presence of the Mediterranean G6PD mutation (S188F) in our HBS
      patients (47.9%) and in controls (16.7%), and this difference was statistically
      significant (p = 0.0017). Additionally, we found that HBS patients homozygous for
      the S188F mutations are at higher risk of developing a stroke (p = 0.002) than
      healthy controls of matching age, sex, and ethnicity. CONCLUSION: G6PD
      Mediterranean S188F codon mutation is common among Saudi sickle cell patients and
      increases the risk of stroke.

PMID- 19594366
TI  - Identification of different genomic deletions and one duplication in the
      dysferlin gene using multiplex ligation-dependent probe amplification and genomic
      quantitative PCR.
AB  - We report for the first time the characterization of disease-causing exonic
      rearrangements in the large-sized gene encoding dysferlin. A newly developed kit
      for multiplex ligation-dependent probe amplification analysis of the dysferlin
      gene was used for a total of 12 samples from patients with suspected diagnosis of
      primary dysferlinopathy. This analysis and subsequent genomic quantitative real
      time PCR evidenced exonic rearrangements in five patients, including four
      different exonic deletions and one duplication. Altogether, our findings confirm
      the existence of exonic rearrangements as disease-causing mutations in primary
      dysferlinopathies.

PMID- 19594367
TI  - Attitudes and anticipated reactions to genetic testing for cancer among patients
      in Mexico City.
AB  - The aim of this study was to investigate the attitudes toward cancer predictive
      genetic testing in a group of non-high-risk women and men and to analyze the
      factors that may influence their intention to use these tests. We studied a
      sample of 859 outpatient women and men attending the four tertiary care hospitals
      of the ISSSTE (Institute of Social Security and Services for Government
      Employees) in Mexico City. Subjects between the ages of 30 and 74 years with no
      present or past history of cancer were asked to answer a questionnaire through
      face-to-face interview. Two different questionnaires were designed, one for women
      and the other for men, regarding genetic testing of a high-risk gene for breast
      and prostate cancer, respectively. Descriptive statistics and univariate
      comparisons were carried out using chi-square test, Wilcoxon's signed rank test,
      and Friedman test. Multivariate analysis was performed using logistic regression
      technique. Results showed that the majority of women attended clinics for regular
      check-ups and for performing screening tests to detect breast cancer, and men did
      not follow this pattern regarding prostate cancer. Women were more motivated to
      get genetic testing, more aware about its benefits, and more concerned about
      having cancer than men.

PMID- 19594368
TI  - Distribution of cytokine gene polymorphisms in the general Lebanese population:
      the first report.
AB  - CONTEXT: Cytokines are polypeptide regulatory molecules that play a significant
      role in inflammatory and regulatory responses of the immune system. Several
      cytokine gene polymorphisms have been studied to date and have been found to be
      associated with distorted cytokine production or activity by affecting
      transcriptional regulation and with vulnerability to a variety of infectious and
      autoimmune diseases as well as to transplant rejection. RESULTS: We studied 106
      healthy Lebanese individuals using polymerase chain reaction/sequence-specific
      priming technique to detect 22 single-nucleotide polymorphisms within 13 cytokine
      genes: IL1alpha 889-T/C, IL1beta 511-T/C, IL1beta +3962-T/C, IL1R pst1 1970-T/C,
      IL1RA mspa1 11100-T/C, IL4Ralpha 1902-G/A, IL12 1188-C/A, IFNgamma 874-A/T,
      TGFbeta codon 10-C/T, TGF-beta codon 25-G/C, TNFalpha 308-A/G, TNFalpha 238-A/G,
      IL2 166-G/T, IL2 330-T/G, IL4 1098-T/G, IL4 590-T/C, IL4 33-T/C, IL6 174-C/G, IL6
      nt565-G/A, IL10 1082-G/A, IL10 819-C/T, and IL10 592-A/C. We compared our results
      to those reported in other populations with similarities observed between the
      Lebanese and the Italian populations. CONCLUSION: The study of different cytokine
      polymorphisms will aid in understanding the susceptibility of populations to
      various diseases, and this is the first report from the Lebanese community.

PMID- 19594369
TI  - Prevalence of the C677T single-nucleotide polymorphism in the
      methylenetetrahydrofolate reductase gene among Pakistani ethnic groups.
AB  - Methylenetetrahydrofolate reductase is an important enzyme in metabolism of
      homocysteine, and a mutation in the gene predisposes individuals to several
      disorders related to homocysteine levels. Polymorphism at C677T shows marked
      heterogeneity based upon ethnicity and geographical location. Pakistani
      population consists of various ethnic groups confined to different regions of the
      country where congenital and genetic defects are a major health concern. We have
      analyzed the distribution of C677T alleles in different Pakistani ethnic groups.
      A cross-sectional study was conducted from all the four provinces of the country
      with samples representing the 14 different ethnic clans. A questionnaire with
      details of their ethnic origin was used, and informed consent was obtained. Blood
      samples from 701 individuals were collected for DNA isolation and subsequent
      C677T single-nucleotide polymorphism determination. The data were statistically
      analyzed. The study revealed that genotypic frequency for CC varied from 0.89
      (Mohanna) to 0.38 (Hazara), CT from 0.56 (Hazara) to 0.11 (Mohanna), and TT from
      0.06 to 0. Our data revealed a varied distribution of C677T mutation. This
      information could be helpful for designing future public health strategies, as it
      can be used to predict the prevalence of several disorders associated with
      genetic predisposition due to methylenetetrahydrofolate reductase C677T alleles.

PMID- 19594370
TI  - Prenatal identification of a novel R937P L1CAM missense mutation.
AB  - The L1 cell adhesion molecule (L1CAM) is a protein encoded by a gene that has
      been localized to Xq28, is a member of the immunoglobulin superfamily of neuronal
      cell adhesion molecules, and plays a role in CNS development and maturation.
      L1CAM is expressed in neurons and Schwann cells, where it is active in neurite
      overgrowth, adhesion fasciculation, migration, myelination, and axon guidance.
      Mutations within the gene have been associated with phenotypic changes that
      include hydrocephalus due to aqueductal stenosis, agenesis or hypoplasia of the
      corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia,
      and adducted thumbs. Here, we present a 19-year-old primigravida Caucasian woman
      who was referred to us in the 27th week of the pregnancy because of fetal
      polyhydramnios and ventriculomegaly. Our evaluation identified a male fetus with
      hydrocephalus, ventriculomegaly, aqueductal stenosis, and polyhydramnios. An
      amniocentesis was performed, and isolated fetal DNA revealed a hemizygous G > C
      mutation in codon 2809 of exon 21 of the L1CAM gene. The patient was later tested
      and identified to be a carrier of the same mutation. The fetus was delivered
      during the 38th week. Neonatal physical examination revealed marked frontal
      bossing, contractures of the feet with rocker bottom appearance, and hyperactive
      reflexes with ankle and knee clonus. He died at 4 months of life.

PMID- 19594371
TI  - Haplotype of the C61G BRCA1 mutation in Polish and Jewish individuals.
AB  - Recurring mutations in the BRCA1 gene are noted in some populations and represent
      either founder mutations or a mutational hot spot. The C61G*BRCA1 (c.181T>G)
      missense mutation is a pathogenic one commonly reported in Polish individuals. A
      Jewish non-Ashkenazi family (of Italian ancestry) was found to carry this
      mutation, and the present study aimed at evaluating whether this mutation
      represents a founder mutation or a mutational hot spot. To that end, multilocus
      allelotyping using five markers intragenic to and flanking the BRCA1 gene
      spanning a genomic region of approximately 1.5 Mbp was carried out in that family
      and in 20 unrelated Polish C61G*BRCA1 mutation carriers. Phasing was done using
      affected and unaffected Jewish family members. The alleles that compose the
      pathogenic, mutation-carrying intragenic BRCA1 haplotype of the Jewish mutation
      carriers were detected in 18/20 Polish mutation carriers. The two flanking
      markers farthest away showed more diversity, between and even within Polish
      individuals. In conclusion, the *BRCA1 missense mutation is a founder mutation
      that can be detected in geographically related populations.

PMID- 19594372
TI  - MTHFR C677T genotype frequency in patients of Middle Eastern descent as
      determined by real-time PCR and melting curve analysis.
AB  - The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism
      produces an elevation in plasma homocysteine concentrations when present in the
      homozygous state. Increased homocysteine levels have been associated with a
      greater risk for vascular diseases, including cardiovascular disease and ischemic
      stroke. In this study, we genotyped 42 nucleic acid samples for the C677T allele
      from our database of Middle Eastern patients as routine validation of the MTHFR
      677C>T assay. Our study is the first to evaluate MTHFR C677T genotype frequency
      in a population of Middle Eastern patients residing in the United States. Among
      the patients, 47.6% were wild type, 40.5% were heterozygous, and 11.9% were
      homozygous for the C677T variant. Although C677T genotype frequency in our
      patient population is slightly higher than that reported by Golbahar et al.
      (2005), statistical analysis showed no statistically significant difference
      beyond chance in genotype profiles (chi(2) = 1.54, df = 2, p = 0.1675). However,
      our findings implicate the need for a larger sample size to explore the need to
      implement standard clinical screening of MTHFR 677C>T. We also highlight the
      robust, reliable, and reproducible assay afforded by the use of anchor and sensor
      hybridization probes within the LightCycler platform to perform amplification and
      melting curve analysis protocols. Melting curve profiles that are produced
      display distinct and robust T(m) peaks based on the degree of anchor and sensor
      hybridization to amplicons produced from template DNA that is either wild-type,
      heterozygous, or a homozygous variant at the MTHFR 677C>T locus. A 10 degrees C
      gap between T(m) peaks allows for rapid and accurate qualitative identification
      of genotype.

PMID- 19594373
TI  - Functional results 1 year after laser vaporization of the prostate: the impact of
      age.
AB  - PURPOSE: To test the hypothesis that age affects functional results after 80W
      photoselective vaporization of the prostate (PVP). PATIENTS AND METHODS: In 156
      patients who were undergoing PVP for benign prostatic hyperplasia (BPH), we
      assessed the International Prostate Symptom Score (IPSS) and Quality of Life
      (QoL) score preoperatively and at 12 months. We calculated the association
      between age and IPSS and QoL results and corrected it for prostate-specific
      antigen (PSA) value, whose impact on PVP functional results is well accepted.
      RESULTS: Median patient age was 66 years (interquartile range [IQR] 62-75),
      median preoperative IPSS 20.5 (IQR 15-25) and QoL 4 (IQR 3-5). At 12 months, the
      median IPSS percent decrease was 58.8% (range 33%-75%), and the median QoL
      percent decrease was 66.7% (range 25%-80%). Age was independently associated with
      both (P < 0.05). In contrast, after adjustment for age, PSA was not significantly
      associated with percent IPSS decrease (P = 0.561), and its association with QoL
      was at the limit of significance (P = 0.05). CONCLUSIONS: Age independently and
      strongly affects IPSS and QoL results at 12 months after 80W PVP.

PMID- 19594374
TI  - Bowel displacement for CT-guided tumor radiofrequency ablation: techniques and
      anatomic considerations.
AB  - PURPOSE: To describe safety and efficacy of bowel displacement techniques and
      determine lesion characteristics that are likely to necessitate bowel
      displacement. PATIENTS AND METHODS: A retrospective review of patients who
      underwent CT-guided renal tumor radiofrequency ablation (RFA) (January 2006
      August 2008) was conducted. Techniques included hydrodissection, additional
      manual torquing of the RFA probe, and additional angioplasty balloon
      interposition. The goal was to displace bowel from the probe by at least 10 to 20
      mm. Air-filled balloon interposition was intended as a thermal barrier. Pre- and
      postbowel displacement distances were measured by CT. Saline volumes were
      recorded. Multivariate stepwise regression analysis was used to determine the
      influence of laterality, renal location, and morphology of renal lesions on their
      proximity to the colon and use of bowel displacement techniques. RESULTS: RFA was
      performed on 57 consecutive patients. Eleven (19%) patients had bowel
      displacement attempts. Median pre-RFA lesion edge to colon distance for
      nondisplaced vs displaced was 43 mm (range 10-100 mm) vs 6 mm (range 0-16 mm),
      respectively (P < 0.05). Two variables were significant for bowel displacement (F
      ratio = 4.681, P = 0.006): Tumor position within the kidney in the craniocaudal
      plane (P = 0.014) and anterior-posterior plane (P = 0.007). Lower pole and
      posterior lesions tended to be closer to the colon and more likely to necessitate
      bowel displacement. Orientation in the medial-lateral plane (P = 0.77) and
      exophytic nature of the lesion (P = 0.83) were not significant features.
      Hydrostatic bowel displacement was always the first-line technique and was
      completely and partly successful in 8 (73%) and 1 (9%) attempts, respectively.
      Partial success was augmented by probe torquing (distance increased from 1 mm to
      16 mm and then to 23 mm with torquing). Mean saline injection: 105 mL (range 55
      440 mL). There were two complete failures (18%) in which bowel was displaced only
      by 0 to 2 mm despite injection of 280 to 440 mL. Balloon interposition was
      attempted in these two cases. Five minor complications occurred in the
      nondisplaced cohort. No complications occurred in the bowel displacement cohort.
      CONCLUSION: Lower pole, posterior renal lesions are more likely to necessitate
      bowel displacement. Bowel displacement techniques are effective and safe in
      displacing bowel.

PMID- 19594375
TI  - Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary
      clot retention in an in vitro model.
AB  - INTRODUCTION: The management of urinary clot retention and hematuria involves
      manual irrigation with sterile water or normal saline via a Foley catheter
      followed by continuous bladder irrigation. Irrigation may become difficult
      because of the formation of dense blood clots. Tissue plasminogen activator (t
      PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of
      manual irrigation of large, dense clots. The goal of the current study was to
      compare t-PA to sterile water for clot irrigation in an in vitro model. MATERIALS
      AND METHODS: In vitro models of clot retention were created using 500-cc urinary
      leg bags each filled with 80 cc of unpreserved whole blood from a healthy
      volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot
      formation. Four models each with 25 mL solution of t-PA at concentrations of 2,
      1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile
      water). Models were instilled with solution (t-PA or control) and incubated for
      30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley
      by a blinded investigator. Three separate experiments were conducted, and
      statistical analysis was performed comparing various irrigation parameters.
      RESULTS: Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg)
      was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water
      control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA
      solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the
      control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180
      mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in
      efficacy for the lower doses of t-PA, but this was not statistically significant.
      CONCLUSION: In this in vitro study, a single 25 mL instillation of t-PA solution
      2 mg/mL is significantly better than sterile water alone for clot evacuation. In
      vivo animal studies are pending.

PMID- 19594376
TI  - Importance of mRNA secondary structural elements for the expression of influenza
      virus genes.
AB  - Development of novel vaccines and therapeutics often requires efficient
      expression of recombinant viral proteins. Here we show that mutations in
      essential functional regions of conserved influenza proteins NP and NS1, lead to
      reduced expression of these genes in vitro. According to in silico analysis,
      these mRNA regions possess distinct secondary structures sensitive to mutations.
      We identified a novel structural feature within a region in NS1 mRNA that encodes
      amino acids essential for NS1 function. Mutations altering this mRNA element lead
      to significantly reduced protein expression. Conversely, expression was not
      affected by mutations resulting in amino acid substitutions, when they were
      designed to preserve this secondary RNA structural element. Furthermore, altering
      this structure significantly reduced RNA transcription without affecting mRNA
      stability. Therefore, distinct internal secondary structures of viral mRNA may be
      important for viral gene expression. If such elements encode amino acids
      essential for the protein function, then early selection against mutations in
      this region will be beneficial for the virus. This might point at yet another
      mechanism of viral evolution, especially for RNA viruses. Finally, introducing
      mutations into viral genes while preserving their secondary RNA structure,
      suggests a new method for the generation of efficiently expressed recombinants of
      viral proteins.

PMID- 19594377
TI  - Chaotic genetic algorithm for gene selection and classification problems.
AB  - Pattern recognition techniques suffer from a well-known curse, the dimensionality
      problem. The microarray data classification problem is a classical complex
      pattern recognition problem. Selecting relevant genes from microarray data poses
      a formidable challenge to researchers due to the high-dimensionality of features,
      multiclass categories being involved, and the usually small sample size. The goal
      of feature (gene) selection is to select those subsets of differentially
      expressed genes that are potentially relevant for distinguishing the sample
      classes. In this paper, information gain and chaotic genetic algorithm are
      proposed for the selection of relevant genes, and a K-nearest neighbor with the
      leave-one-out crossvalidation method serves as a classifier. The chaotic genetic
      algorithm is modified by using the chaotic mutation operator to increase the
      population diversity. The enhanced population diversity expands the GA's search
      ability. The proposed approach is tested on 10 microarray data sets from the
      literature. The experimental results show that the proposed method not only
      effectively reduced the number of gene expression levels, but also achieved lower
      classification error rates than other methods.

PMID- 19594378
TI  - Why do young adults develop a passion for Internet activities? The associations
      among personality, revealing "true self" on the Internet, and passion for the
      Internet.
AB  - This study examines the associations of harmonious passion (HP) and obsessive
      passion (OP) for Internet activities with Eysenckian personality dimensions in a
      sample of 421 university students. Results show that psychoticism correlates
      positively with both HP and OP; extroversion correlates positively with HP only;
      and neuroticism has no correlation with passion for Internet activities.
      Additionally, the study examines participants' tendency to express their "true
      self" on the Internet, and the results reveal that this tendency has a positive
      association with psychoticism, neuroticism, and both types of passion for the
      Internet. Moreover, the relationship between psychoticism and passion (both
      harmonious and obsessive) is mediated by the tendency to express true self on the
      Internet. The results were interpreted from the media dependency perspective.

PMID- 19594379
TI  - Social responsibility tools in online gambling: a survey of attitudes and
      behavior among Internet gamblers.
AB  - To date, little empirical research has focused on social responsibility in
      gambling. This study examined players' attitudes and behavior toward using the
      social responsibility tool PlayScan designed by the Swedish gaming company
      Svenska Spel. Via PlayScan, players have the option to utilize various social
      responsibility control tools (e.g., personal gaming budgets, self-diagnostic
      tests of gambling habits, self-exclusion options). A total of 2,348 participants
      took part in an online questionnaire study. Participants were clientele of the
      Svenska Spel online gambling Web site. Results showed that just over a quarter of
      players (26%) had used PlayScan. The vast majority of those who had activated
      PlayScan (almost 9 in 10 users) said that PlayScan was easy to use. Over half of
      PlayScan users (52%) said it was useful; 19% said it was not. Many features were
      seen as useful by online gamblers, including limit setting (70%), viewing their
      gambling profile (49%), self-exclusion facilities (42%), self-diagnostic problem
      gambling tests (46%), information and support for gambling issues (40%), and
      gambling profile predictions (36%). In terms of actual (as opposed to
      theoretical) use, over half of PlayScan users (56%) had set spending limits, 40%
      had taken a self-diagnostic problem gambling test, and 17% had used a self
      exclusion feature.

PMID- 19594380
TI  - Electronic game play and school performance of adolescents in southern Thailand.
AB  - Increasing exposure of children and adolescents to electronic media is a
      worldwide phenomenon, including in Thailand. To date, few studies examine
      electronic game play in Thai adolescents. Our research describes the prevalence
      of electronic game play and examines associations between the time spent engaged
      in electronic game play and school performance of adolescents in Hat-Yai
      municipality. A cross-sectional study was conducted among 1,492 adolescents from
      four secondary schools and one commercial college from January through March
      2007, using questionnaires for collecting information about demographic data,
      school grades, and electronic game play behaviors. The prevalence of electronic
      game play was 75% in boys and 59% in girls. Twenty-two percent of boys and 8.7%
      of girls played electronic games every day with more than 2 hours per session.
      The two most common places of game play were at game shops (71%), followed by at
      their own home (70%). Using linear regression analysis, the "low user or less
      than 2 hours per session" game players and females were less likely to have
      school grades below 3.00 with adjusted odds ratios of 0.44 (95% CI 0.25-0.80, p =
      0.004) and 0.49 (95% CI 0.30-0.76, p = 0.005) respectively. This study finds that
      excessive playing of electronic games is associated with school grades below
      3.00.

PMID- 19594381
TI  - Cyberbullying: the new face of workplace bullying?
AB  - While the subject of cyberbullying of children and adolescents has begun to be
      addressed, less attention and research have focused on cyberbullying in the
      workplace. Male-dominated workplaces such as manufacturing settings are found to
      have an increased risk of workplace bullying, but the prevalence of cyberbullying
      in this sector is not known. This exploratory study investigated the prevalence
      and methods of face-to-face bullying and cyberbullying of males at work. One
      hundred three surveys (a modified version of the revised Negative Acts
      Questionnaire [NAQ-R]) were returned from randomly selected members of the
      Australian Manufacturing Workers' Union (AMWU). The results showed that 34% of
      respondents were bullied face-to-face, and 10.7% were cyberbullied. All victims
      of cyberbullying also experienced face-to-face bullying. The implications for
      organizations' "duty of care" in regard to this new form of bullying are
      indicated.

PMID- 19594382
TI  - A new rating scale for open-field evaluation of behavioral recovery after
      cervical spinal cord injury in rats.
AB  - The Basso, Beattie, Bresnahan (BBB) locomotor rating scale has proven a reliable
      tool to evaluate impairments of hindlimb locomotor skills after thoracic spinal
      cord injury (SCI). With the increasing use of cervical SCI rat models, there is a
      critical need to develop scoring scales designed to more precisely examine
      alteration and recovery of forelimb functions. The main goal of the present study
      was to elaborate and evaluate a new rating scale for open-field testing of the
      fore- and hindlimb locomotor functions after cervical SCI. We also assessed the
      effectiveness of this rating scale for discriminating the functional consequences
      of dorsolateral (Hdl group), lateral (Hl group), or complete C4 unilateral
      hemisections (Hc group). Our findings show that the new rating scale can be
      considered as a sensitive and reliable descriptor of the postoperative time
      course of deficits affecting differentially the fore- and hindlimb sensorimotor
      functions following injuries of various severities. This new method provides
      reproducible data and can be used reliably by non-expert examiners. The proposed
      rating scale appears to be a useful tool for the assessment of various treatments
      designed to promote functional recovery after SCI. See online Supplementary
      Material (scoring spreadsheet and videotape recordings) at www.liebertonline.com.

PMID- 19594383
TI  - The influence of enrollment criteria on recruitment and outcome distribution in
      traumatic brain injury studies: results from the impact study.
AB  - Substantial heterogeneity exists among patients who suffer from traumatic brain
      injury (TBI). Strict enrollment criteria may diminish heterogeneity in randomized
      controlled trials (RCTs), but will also decrease recruitment and may affect the
      outcome distribution. The aim of this study was to investigate the influences of
      commonly used enrollment criteria for RCTs in TBI on potential recruitment and on
      outcome distribution. We used individual patient data from the International
      Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) database,
      including six therapeutic phase III RCTs (n = 5816) and three surveys (n = 2217)
      in TBI. The primary outcome was the Glasgow Outcome Scale (GOS) at 6 months after
      injury, which we dichotomized as favorable/unfavorable. We investigated the
      influences of commonly used enrollment criteria on recruitment and outcome
      distribution: time window between injury and admission to study hospital <or= 8
      h; age at injury <or= 65 years; >or= 1 reactive pupil; motor score > 1; Glasgow
      Coma Scale <or= 8. Application of all enrollment criteria resulted in a large
      reduction of recruitment in both the surveys (up to 65%) and the RCTs (up to
      41%). Among the remaining patients, fewer had an unfavorable outcome in both the
      surveys (original, 60%; remaining, 44%) and the RCTs (original, 43%; remaining,
      38%). Applying these enrollment criteria to patients from the surveys resulted in
      an outcome distribution that approximated the outcome observed in the RCTs. The
      use of strict enrollment criteria leads to substantial reductions in the
      recruitment of RCTs in TBI. The outcome in TBI studies depends strongly on the
      enrollment criteria.

PMID- 19594386
TI  - Nuclear and nucleolar reprogramming during the first cell cycle in bovine nuclear
      transfer embryos.
AB  - The immediate events of genomic reprogramming at somatic cell nuclear transfer
      (SCNT) are to high degree unknown. This study was designed to evaluate the
      nuclear and nucleolar changes during the first cell cycle. Bovine SCNT embryos
      were produced from starved bovine fibroblasts and fixed at 0.5, 1, 2, 3, 4, 8,
      12, and 16 h postactivation (hpa). Parthenogenetic (PA) embryos were used as
      control. The SCNT and PA embryos were processed for lacmoid staining,
      autoradiography, transmission electron microscopy (TEM), and immunofluorescence
      localization of: upstream binding factor (UBF) and fibrillarin at 4 and 12 hpa.
      Likewise, starved and nonstarved fibroblasts were processed for autoradiography
      and TEM. The fibroblasts displayed strong transcriptional activity and active
      fibrillogranular nucleoli. None of the reconstructed embryos, however, displayed
      transcriptional activity. In conclusion, somatic cell nuclei introduced into
      enucleated oocytes displayed chromatin condensation, partial nuclear envelope
      breakdown, nucleolar desegregation and transcriptional quiescence already at 0.5
      hpa. Somatic cell cytoplasm remained temporally attached to introduced nucleus
      and nucleolus was partially restored indicating somatic influence in the early
      SCNT phases. At 1-3 hpa, chromatin gradually decondensed toward the nucleus
      periphery and nuclear envelope reformed. From 4 hpa, the somatic cell nucleus
      gained a PN-like appearance and displayed NPBs suggesting ooplasmic control of
      development.

PMID- 19594385
TI  - Monitoring hippocampus electrical activity in vitro on an elastically deformable
      microelectrode array.
AB  - Interfacing electronics and recording electrophysiological activity in
      mechanically active biological tissues is challenging. This challenge extends to
      recording neural function of brain tissue in the setting of traumatic brain
      injury (TBI), which is caused by rapid (within hundreds of milliseconds) and
      large (greater than 5% strain) brain deformation. Interfacing electrodes must be
      biocompatible on multiple levels and should deform with the tissue to prevent
      additional mechanical damage. We describe an elastically stretchable
      microelectrode array (SMEA) that is capable of undergoing large, biaxial, 2-D
      stretch while remaining functional. The new SMEA consists of elastically
      stretchable thin metal films on a silicone membrane. It can stimulate and detect
      electrical activity from cultured brain tissue (hippocampal slices), before,
      during, and after large biaxial deformation. We have incorporated the SMEA into a
      well-characterized in vitro TBI research platform, which reproduces the
      biomechanics of TBI by stretching the SMEA and the adherent brain slice culture.
      Mechanical injury parameters, such as strain and strain rate, can be precisely
      controlled to generate specific levels of damage. The SMEA allowed for
      quantification of neuronal function both before and after injury, without
      breaking culture sterility or repositioning the electrodes for the injury event,
      thus enabling serial and long-term measurements. We report tests of the SMEA and
      an initial application to study the effect of mechanical stimuli on neuron
      function, which could be employed as a high-content, drug-screening platform for
      TBI.

PMID- 19594387
TI  - Naturally immortalised mouse embryonic fibroblast lines support human embryonic
      stem cell growth.
AB  - Human embryonic stem cell (hESC) growth is dependent on various factors released
      by feeder cells. Some of them have already been elucidated, although much
      research is still needed to understand the biology of stem cell maintenance in
      culture. Traditionally, primary mouse embryonic fibroblasts (PMEFs) have been
      used as feeder layers, and both murine and human fibroblast cell lines have been
      shown to support pluripotency and self-renewal of hESC. Here we report the
      derivation of three new mouse embryonic fibroblast cell lines, MEFLU-M, MEFLU-T,
      and MEFLU-TB, with different properties regarding growth and support for
      undifferentiated hESCs. MEFLU-TB is able to support continuous growth of the
      newly derived Man-1, as well as H1, HUES-1, HUES-7, HUES-8, and HUES-9 human
      embryonic stem cell lines. After more than 50 passages and doublings, MEFLU-TB
      feeders compare to early passage primary mouse embryonic fibroblasts in their
      ability to support undifferentiated hESC growth. Our results contradict a
      previous paradigm that PMEFs tend to lose their capacity to support proliferation
      of hESCs with increasing passages, and show that the MEFLU-TB mouse embryonic
      fibroblast cell line and its conditioned medium have the potential to support the
      maintenance of hESC lines. Also, our results clearly show that spontaneous
      immortalization of primary fibroblasts can be achieved in culture without any
      chemical addition or genetic modification.

PMID- 19594388
TI  - Optimization of embryo culture conditions for increasing efficiency of cloning in
      buffalo (Bubalus bubalis) and generation of transgenic embryos via cloning.
AB  - Cloning in bovine species is marred by low efficiency of blastocyst formation.
      Any increase in the efficiency of blastocyst formation upon nuclear transfer will
      greatly enhance the efficiency of cloning. In the present study, the effect of
      various media, protein sources, and growth factors on the development of cloned
      buffalo embryos was evaluated. Among various combinations tested, culture of
      cloned embryos in TCM-199 media on the feeder layer of Buffalo Oviductal
      Epithelial Cells (BOEC) in the presence of bovine serum albumin-free fatty acid
      (BSA-FFA) and leukemia inhibitory factor (LIF) provided most suitable environment
      for efficient development of cloned blastocysts. Under these conditions, we
      achieved a blastocyst formation rate of 43%, which is better than those reported
      previously. Because preimplantation embryonic development, in vivo, occurs in an
      environment of oviductal cells, the blastocysts generated by this method may
      presumably be more suitable for implantation and further development.
      Additionally, we generated green blastocysts from enucleated oocytes by transfer
      of nuclei from cells transfected with EGFP transgene, showing possibility of
      transgenesis via cloning in this species. To our knowledge, this is the first
      report regarding the production of transgenic cloned buffalo embryos and their
      developmental competence with respect to various media, cocultures, and
      supplements.

PMID- 19594384
TI  - Metabolic and histologic effects of sodium pyruvate treatment in the rat after
      cortical contusion injury.
AB  - This study determined the effects of intraperitoneal sodium pyruvate (SP)
      treatment on the levels of circulating fuels and on cerebral microdialysis levels
      of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects
      of SP treatment on neuropathology after left cortical contusion injury (CCI) in
      rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP)
      significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001)
      compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also
      increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05),
      but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac)
      levels within the cerebral cortex significantly increased bilaterally (p < 0.05)
      and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased
      significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were
      higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI
      SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and
      the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats
      with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer
      damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but
      three hourly injections of SP (1000 mg/kg) were needed to significantly reduce
      contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment
      increases circulating levels of three potential brain fuels, attenuates a CCI
      induced reduction in extracellular glucose while increasing extracellular levels
      of pyruvate, but not lactate, and can attenuate cortical cell damage occurring
      within 6 h of injury. Enduring (2 week) neuronal protection was achieved only
      with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the
      need for additional fuel throughout the acute period of increased metabolic
      demands induced by CCI.

PMID- 19594389
TI  - Revival of extinct species using nuclear transfer: hope for the mammoth, true for
      the Pyrenean ibex, but is it time for "conservation cloning"?
AB  - Recent accomplishments in the fields of nuclear transfer and genomics, such as
      the cloned offspring production from frozen mouse cells, cryopreserved at not too
      low temperatures without cryoprotectors; or the sequencing of wooly mammoth
      genome, have opened the opportunity for the revival of extinct species. As
      expected, they are receiving a lot of publicity in the media and also scientific
      attention. Furthermore, it was recently published the "revival" of the first
      extinct subspecie: the Pyrenean ibex (Capra pyrenaica pyrenaica), a wild goat
      extinct in 2000. This strengthens the field of cloning as it had been tarnished
      by induced pluripotent stem cells (iPS) and other methods of reprogramming.
      However, for biological conservation purposes, cloning is not generally accepted
      as an alternative for animal conservation, and there is an ongoing debate between
      reproductive scientists and conservation specialists. Although we believe that
      nuclear transfer technologies have an opportunity in conservation efforts for
      some species that are on the brink of extinction and that population status,
      geographical isolation, reproductive characteristics, and human pressure create a
      situation that is almost unsustainable. In this article we discuss the barriers
      in cloning mammoths and cloning controversies in conservation from a zoological
      perspective, citing the species that might benefit from nuclear transfer
      techniques in the arduous journey so as not to disappear forever from this, our
      world.

PMID- 19594390
TI  - Close relatedness between exotic nucleus and cytoplast can improve the
      postimplantation development rate of cloned intersubspecies embryos.
AB  - To improve intersubspecies cloning efficiency, this paper provides six kinds of
      SCNT embryos with different nuclear-cytoplasmic relatedness to compare the
      relatedness on the cloning efficiency. Three kinds of SCNT embryos with different
      relatedness are produced by using Boer goat fibroblast cells as nuclear donors
      and oocytes of Sannen goat, crossbred F1 (Sannen goat x Boer goat) and Boer goat
      as cytoplast recipients. Four kinds of SCNT embryos with different relatedness
      are produced by using Sannen goat oocytes as recipients and fibroblast cells of
      Boer goat, crossbred F2 (crossbred F1 x Boer goat), crossbred F1, and Sannen goat
      as nuclear donors. Results show that no obvious differences were observed for
      preimplantation development of these SCNT embryos. However, different nuclear
      cytoplasmic relatedness resulted in obvious differences for postimplantation
      development of these SCNT embryos. The relatedness is complementary: improving
      either cytoplasmic compatibility relatedness to nucleus or nuclear relatedness to
      cytoplast could reduce the gestation loss rate, and increase the birth rate of
      cloned intersubspecies embryos significantly. But a further amelioration of the
      relatedness did not improve the postimplantation development in direct
      proportion. These results suggested that close nuclear-cytoplasmic relatedness
      can improve the postimplantation development rate of cloned intersubspecies
      embryos.

PMID- 19594391
TI  - Expression of pluripotency-related genes during bovine inner cell mass explant
      culture.
AB  - Recent findings identifying the transcription factors involved in the regulation
      of pluripotency and self-renewal in embryonic stem cells (ESC) may provide keys
      that enable the derivation of ESC in domestic species. In this study we monitored
      the expression of pluripotency-related genes in bovine inner cell mass (ICM)
      explants during the critical first steps in establishment of primary cultures.
      The expression of NANOG and POU5F1 transcripts and proteins in intact, in vitro
      produced (IVP) blastocysts was confirmed by quantitative RT-PCR and fluorescent
      immunocytochemistry. NANOG was localized to the nucleoplasm as well as the
      nucleoli in the ICM, whereas it appeared to be restricted to the nucleoli in
      trophectoderm cells. POU5F1 was localized in the nuclei of ICM and trophectoderm
      cells. ICM explants were analyzed by quantitative PCR and semiquantitative RT
      PCR. The three major pluripotency-related transcription factors, NANOG, POU5F1,
      and SOX2, were expressed initially in the ICM explants, but were downregulated
      with subsequent culture. Markers of differentiation (BMP4, HNF4, NCAM, CDX2) and
      genes involved in LIF, BMP, and WNT signaling pathways were also expressed. ICM
      explants were cultured in the presence of various concentrations of cytokines
      belonging to the TGF-beta superfamily. Noggin, a cytokine inhibiting the BMP4
      pathway, successfully upregulated the relative expression of NANOG mRNA in the
      ICM explants with respect to controls.

PMID- 19594392
TI  - Chromosomal instability of murine adipose tissue-derived mesenchymal stem cells
      in long-term culture and development of cloned embryos.
AB  - Mice are the most commonly used laboratory animals for research, and some mouse
      stem cells, such as induced pluripotent stem cells, embryonic stem cells, and
      mesenchymal stem cells (MSCs), are also widely used in basic research. It is thus
      important to know if these stem cells maintain their genomic stability when
      cultured. Murine bone marrow-derived mesenchymal stem cells (BMSCs) appear to
      undergo spontaneous transformation in vitro. Murine adipose tissue-derived
      mesenchymal stem cells (ADSCs), like BMSCs, have the potential to differentiate
      into multiple lineages. In this study, we used G-banding, induction of multiple
      lineage differentiation, flow cytometry, and nuclear transfer (NT), and found
      that murine ADSCs also displayed chromosomal instability in long-term culture.
      Furthermore, we performed NT using murine ADSCs to study the nuclear
      reprogramming ability of undifferentiated adult stem cells and to find a new
      efficient donor for NT. Using the stem cells did not increase the percentage of
      NT embryos that developed to the morula/blastocyst stage, compared with cloned
      embryos from cumulus cells. This may be because the stem cells displayed
      chromosomal instability. This is the first reported study of the use of ADSCs for
      NT in mice. ADSCs could provide an alternative donor cell type for NT in other
      species, with the advantages of easy harvesting involving little or no pain or
      trauma.

PMID- 19594393
TI  - Swine influenza virus has caused considerable concern around the world.

PMID- 19594394
TI  - Antimicrobial host defense peptides in an arteriviral infection: differential
      peptide expression and virus inactivation.
AB  - Antimicrobial host defense peptides (AHDPs) are effective against a wide range of
      microbes, including viruses. The arteriviral infection caused by porcine
      reproductive and respiratory syndrome virus (PRRSV) is a devastating pandemic
      that causes the most economically significant disease of swine. We sought to
      determine if the expression of AHDPs was influenced by infection with PRRSV, and
      if porcine AHDPs have direct antiviral activity against PRRSV. Because pulmonary
      alveolar macrophages (PAMs) are primary targets of PRRSV infection, gene
      expression of porcine AHDPs was evaluated in lungs from fetal and 2-wk-old
      congenitally infected pigs. In PRRSV-positive lungs and PAMs, gene expression of
      most porcine AHDPs showed little upregulation. However, gene expression of
      porcine beta-defensin-1 (pBD-1), pBD-4, pBD-104, pBD-123, and pBD-125 were
      downregulated more than threefold in 2-wk-old congenitally infected pig lungs.
      Incubation of PRRSV with pBD-3 or PG-4 significantly inhibited viral infectivity
      in MARC-145 cells. Using nine protegrin or protegrin-derived peptides, we
      determined that a cyclic analog of PG-4 increased anti-PRRSV activity, and that
      substitution of phenylalanine with valine eliminated most PG-4 antiviral
      activity. In PAMs, pBD-3 and PG-4 at 5-40 microg/mL consistently suppressed PRRSV
      titers. Collectively, these findings suggest a potential role for some porcine
      AHDPs as innate antiviral effectors in PRRSV infection. Moreover, modulation of
      porcine innate immune mechanisms with AHDPs may be one means of limiting the
      impact of this costly pandemic viral disease.

PMID- 19594395
TI  - Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in
      a murine model of RSV vaccine-enhanced disease.
AB  - Vaccination with formalin-inactivated respiratory syncytial virus (RSV) vaccine
      results in enhanced respiratory tract inflammation and injury following
      subsequent RSV infection. RSV vaccine-enhanced disease can also be produced in
      mice by prior vaccination with a vaccinia virus vector containing the RSV G
      protein, followed by intranasal infectious RSV challenge, a process characterized
      by induction of a potent memory CD4(+) T-cell response to challenge infection
      with some features characteristic of Th-2 CD4(+) T-cell responses, including
      increased eosinophil accumulation in pulmonary inflammatory infiltrates. The
      adaptive immune response to the RSV G protein in immunized BALB/c mice is
      characterized by a weak or absent primary and secondary recall CD8(+) T-cell
      response. These and related results have led to the hypothesis that the failure
      of the infected animals to mount an effective CD8(+) memory T-cell (CD8(+) Tm)
      response in this model could account for the pulmonary eosinophilia associated
      with the development of enhanced disease, and that CD8(+) T cells may control the
      development of eosinophilia. In this study, we investigated how and when the
      generation of a CD8(+) Tm response to RSV infection might affect the development
      of pulmonary eosinophilia in this model of vaccine-enhanced disease. By defining
      the CD8(+) T-cell response kinetics and monitoring lung parenchymal eosinophil
      accumulation, we show that the establishment of an RSV-specific CD8(+) Tm
      response in the infected lungs early after challenge infection (i.e., within the
      first 3 d of RSV infection) is necessary and sufficient to control pulmonary
      eosinophilia development. Additionally, our work suggests that the mechanism by
      which CD8(+) T cells regulate this process is not by modulating the
      differentiation or development of the CD4(+) Tm response. Rather, we demonstrate
      that IL-10 produced by early responding CD8(+) Tm cells may regulate the
      pulmonary eosinophilia development observed in RSV vaccine-enhanced disease.

PMID- 19594396
TI  - Analysis of the immune response to Hantaan virus nucleocapsid protein C-terminal
      specific CD8(+) T cells in patients with hemorrhagic fever with renal syndrome.
AB  - Hantaan virus (HTNV), the prototype member of the Hantavirus genus in the family
      Bunyaviridae, causes hemorrhagic fever with renal syndrome (HFRS), which is
      characterized by capillary leakage, hemorrhage, and renal injury, and is an
      important public health problem in China. Some kinds of immune cells,
      particularly CD8(+) T cells, are involved in the pathogenesis of Hantavirus
      infection. The nucleocapsid protein (NP) of the Hantavirus is the most conserved
      structural protein and the most abundant viral protein produced during infection.
      It is one of the important target antigens that induce the CD8(+) T-cell
      response. In this study, we examined the CD8(+) T-cell response to HTNV NP C
      terminal polypeptides. We synthesized 23 overlapping C-terminal polypeptides and
      detected the antigen-specific CD8(+) T cell response in 15 patients with HFRS.
      The results demonstrated that there were NP-specific T-cell responses in bulk
      cultures of peripheral blood mononuclear cells (PBMCs) from 9 of 15 patients. The
      peptide 51 (aa 301-315: SPSSIWVFAGAPDRC), peptide 60 (aa 355-369:
      LRKKSSFYQSYLRRT), and peptide 70 (aa 415-429: DVKVKEISNQEPLKL) induced strong
      CD8(+) T-cell responses. Among them, peptide 70 induced CTL responses in donors
      7, 9, and 11, and the strongest responses were seen in donor 11. Depletion of
      CD8(+) T cells from PBMCs completely abrogated the peptide-specific T-cell
      response, while depletion of CD4(+) T cells did not diminish the number of IFN
      gamma spot-forming cells. These data suggest that infection with HTNV results in
      CTL responses to immunodominant regions on the NP.

PMID- 19594397
TI  - Changes in lymphocyte subsets and cytokines during European porcine reproductive
      and respiratory syndrome: increased expression of IL-12 and IL-10 and
      proliferation of CD4(-)CD8(high).
AB  - The changes in peripheral blood mononuclear cells (PBMCs) have been studied in
      several reports in an attempt to determine the immune response against porcine
      reproductive and respiratory syndrome virus (PRRSV) infection. However, how these
      changes are evoked after PRRSV infection has not yet been clarified. The aim of
      this study was to analyze the changes seen in lymphocyte subsets and
      immunomodulatory cytokine expression in pigs after an acute experimental
      infection with a European PRRSV field isolate. Pigs were inoculated
      intramuscularly with PRRSV field isolate 2982. Samples from blood, medial
      retropharyngeal and tracheobronchial lymph nodes, and spleen were collected at
      different time points for flow cytometry studies and for cytokine expression by
      ELISA. CD21(+) cell counts increased in PBMCs and tracheobronchial lymph node
      cells from 17 to 24 dpi, coinciding with an increase in PRRSV-specific antibody
      titer in blood. CD3(+) T-cell counts increased mainly due to an enhancement of
      CD4(-)CD8(high) and CD4(+)CD8(+) T cells. CD4(-)CD8(low) T cells were decreased
      in all organs studied, whereas CD4(+)CD8(-) T cells decreased only in the spleen.
      The drop in viremia correlated with an enhancement of CD4(-)CD8(high) T cells,
      and with a higher expression of interleukin-10 (IL-10) and interleukin-12 p40 (IL
      12 p40). No efficient interferon-gamma (IFN-gamma) response was detected during
      the acute phase of the infection, and the expression of interferon-alpha (IFN
      alpha) was late and reached its maximum expression once the viremia decreased.
      These results point to IL-10 and IL-12 as cytokines that might play a significant
      role in the PRRSV immune response, as may CD4(-)CD8(high) T cells.

PMID- 19594398
TI  - Virus-like particle vaccine comprised of the HA, NA, and M1 proteins of an avian
      isolated H5N1 influenza virus induces protective immunity against homologous and
      heterologous strains in mice.
AB  - Highly pathogenic avian influenza H5N1 virus represents a growing threat for an
      influenza pandemic. Development of effective vaccines for H5N1 is a priority for
      pandemic preparedness. Focusing on influenza virus-like particles (VLPs) has been
      suggested as a promising vaccine approach. Recent VLP vaccination efforts have
      been concentrated on the H5N1 strains isolated from humans. Because all confirmed
      cases of human H5N1 infection were directly transmitted from infected poultry, it
      is of interest to develop VLP vaccines comprised of antigenic proteins of avian
      H5N1 strains in order to compare their efficacy in fighting diverse H5N1 strains
      with vaccines developed using human isolates. In this study, we generated a VLP
      vaccine composed of the HA, NA, and M1 proteins of the avian H5N1 influenza virus
      isolate A/chicken/Hubei/489/2004, which seems to occupy a unique phylogenetic
      position; it belongs to neither clade 1 nor clade 2. Upon infection of Sf9 insect
      cells using recombinant baculoviruses, the co-expressed HA, NA, and M1 proteins
      self-assembled and released into the culture medium as VLPs. In a mouse model,
      purified VLPs elicited an effective antibody response and conferred complete
      protection against heterologous human H5N1 influenza virus, as well as a
      homologous avian H5N1 influenza virus isolate. Our work provides further evidence
      that vaccination with influenza VLPs may be a productive approach to achieve
      protection against diverse H5N1 strains.

PMID- 19594399
TI  - Analysis of colour stability of selected provisional prosthetic materials: an in
      vitro study.
AB  - Prosthetic restorative materials (that are) used for temporary fixed dentures
      tend to exhibit variable discolouration over several weeks of use. The aim of
      this study was to perform a spectrophotometric analysis of the influence of
      selected discolouring factors on the colour stability of provisional prosthetic
      materials in vitro. In the study, the following prosthetic materials for short
      term use in the oral cavity were evaluated: Luxatemp, Structur 2S.C., Protemp II,
      Zhermacryl STC and Dentalon Plus. Samples of these materials were immersed in
      coffee, tea and dark fruit juice for 60 h at different pH values. Colour was
      evaluated by determining the monochromatic coefficients of light reflected by the
      samples, using a spectrophotometric method. Results received in artificial light
      (illuminant A) were compared with those obtained in daylight (illuminant D65).
      Changes in colour and its parameters according to the CIE L*a*b* system were
      analysed. The analysis (of the colour and colour parameters) of the tested
      materials in two types of light showed that Structur displayed the greatest
      tendency to discolouration and that the least tendency to discolouration was
      exhibited by Dentalon Plus. The fact that colour parameters obtained in two types
      of light were not identical suggests that changes in the colour of the same
      material may be perceived differently, depending on the illuminant. Provisional
      prosthetic materials show variable colour stability under different conditions in
      the oral cavity. The colour of prosthetic materials may be perceived differently,
      depending on the illuminant and the effect of the environment in which they are
      used.

PMID- 19594400
TI  - Simulations and experiments of the balloon dilatation of airway stenoses.
AB  - This article investigates the mechanics of balloon dilatation in the treatment of
      bronchotracheal stenosis. The "scar stricture"-type stenosis examined in this
      paper is typically dilated manually, using a dilatation balloon. If indicated,
      this is followed by stent implantation. The selection of the stent with proper
      characteristics is performed empirically, based on personal experience and
      preference. In order to optimize the therapeutic outcome, however, it is
      necessary to match the stent with the stress-strain properties of the stenosis,
      which are not determined during manual balloon dilatation. The objective is to
      utilize models to experimentally and theoretically establish the correlation
      between the pressure/volume curve measured during the dilatation and the stress
      strain properties of the stenosis, taking into account that during dilatation of
      scar strictures the balloon is only partially compressed, as it extends beyond
      both ends of the stenosis. Experiments are carried out using stenosis models with
      various extensibilities and lengths. As expected, more hardened stenosis resulted
      in steeper pressure/volume curves during the dilatation. On the other hand, the
      comparison between stenosis of equal extensibilities, but different length,
      showed an initially unexpected larger distension of the shorter stenosis, at
      equal pressure increases. This is caused by the fact that the margins of the
      stenosis are allowed more time to distend, compared to the central areas of the
      stenosis. The term "effect of margin expansion" was introduced to describe this
      behavior. The modeling of the dilatation process is based on the equilibrium
      conditions of cut-free balloon portions. The balloon/stenosis system is divided
      into three areas with different characteristics: (1) the proximal and distal area
      of the balloon outside the stenosis; (2) the area of contact between the balloon
      and the stenosis; and (3) the transition area between (1) and (2). Numerical
      simulations of the balloon dilatation confirm the conclusions from the
      experimental results and the theoretical considerations regarding the correlation
      between the pressure/volume curve of the dilatation and the stress-strain
      properties of the stenosis.

PMID- 19594401
TI  - Label-free optical biosensor: a tool for G protein-coupled receptors pharmacology
      profiling and inverse agonists identification.
AB  - Current GPCR cell-based assays often rely on the measurement of a loaded
      fluorescent dye, fluorescently tagged targets, or the expression of a reporter.
      These manipulations may alter the cellular physiology of the target GPCR, and the
      measurements may be subject to off-target interference of compounds. Label-free
      optical biosensor-based technologies that provide a noninvasive methodology to
      study GPCR activation and signaling have been developed. These technologies
      enable the evaluation of drug effects on various GPCRs that couple to different
      signal transduction pathways using only one assay platform. This technology is
      highly sensitive and detects inverse agonism, therefore providing a convenient
      tool to study the pharmacology of drugs. Furthermore, its real-time kinetic
      measurements give researchers additional information about the biological
      responses induced by the drug. This assay platform when applied in early drug
      discovery efforts can provide valuable information on the mechanism of action and
      pharmacology profiles of drug candidates.

PMID- 19594402
TI  - Serum procollagen type III is associated with elevated right-sided filling
      pressures in stable outpatients with congestive heart failure.
AB  - Elevated filling pressures are associated with heart failure deterioration, but
      mechanisms underlying this association remain poorly understood. We sought to
      investigate whether or not elevated filling pressures are associated with
      increased collagen turnover, evaluated by procollagen type III aminoterminal
      peptide (PIIINP) levels, in stable systolic heart failure. Eighty patients with
      heart failure with severe systolic dysfunction (ejection fraction 26 +/- 7%) were
      included. Patients underwent simultaneous echocardiogram with evaluation of
      haemodynamic parameters and blood sampling for PIIINP measurement. Mean PIIINP
      level was 6.11 +/- 2.62 microg l(-1). PIIINP was positively associated with
      estimated right atrial pressure (RAP) (r = 0.36; p = 0.001). Mean PIIINP values
      were 5.04 +/- 2.42 microg l(-1) in patients with estimated RAP < or = 5 mmHg, and
      7.59 +/- 2.54 microg l(-1) in those with RAP > 15 mmHg (p < 0.01). In conclusion,
      elevated right-side filling pressures are associated with evidence of active
      extracellular matrix turnover, as indicated by elevated PIIINP levels, in stable
      systolic heart failure. Activation of extracellular matrix turnover may be
      implicated in the accelerated progression of heart failure syndromes seen in
      patients with persistent congestion.

PMID- 19594405
TI  - Oxidation of endobiotics mediated by xenobiotic-metabolizing forms of human
      cytochrome.
AB  - Cytochrome P450s (P450 or CYPs) comprise a superfamily of enzymes that catalyze
      the oxidation of a wide variety of xenobiotic chemicals including drugs and
      environmental carcinogens. Recent studies have demonstrated that endogenous
      chemicals are also oxidized by human P450s which mainly metabolize xenobiotics.
      In this review, we summarize the expected physiological significance of the
      biotransfornation as well as Michaelis-Menten constants (Km), maximal velocities
      (Vmax), Vmax/Km (intrinsic clearance) values, and/or metabolic activities for 33
      endogenous substrates, including (1) arachidonic acid and fatty acids, (2)
      steroid hormones, such as testosterone, progesterone, and allopregnanolone, (3)
      amines, such as tyramine, and (4) lipid-soluble vitamins, such as retinol and
      vitamin D3 analogues, mediated human P450 isoforms consisting of so-called drug
      metabolizing enzymes for the purpose of predicting the key enzyme(s) in vivo.
      Arachidonic acid is metabolized via the epoxidation and omega-hydroxylation to
      many biologically active eicosanoids such as epoxyeicosatrienoic acids and
      hydroxyeicosatetraenoic acids by multiple P450 isoforms including CYP2C, CYP2E1
      and CYP4A11. CYP2D in the brain may be involved in the metabolism of neuronal
      amines and steroids and in the regulation of the central nervous system. CYP1A2
      and CYP3A4 appear to be the major P450 enzymes catalyzing the oxidation of all
      trans-retinol to all-trans-retinoic acid in human liver, and CYP3A4 is one of the
      vitamin D3 25-hydroxylases. Although the significance of the contribution is
      still unknown in detail, the collective findings provide fundamental and useful
      information for the biological contribution of the metabolism of endogenous
      substances by drug-metabolizing enzymes, P450s. In addition, genetic polymorphism
      of these drug-metabolizing P450s may affect the metabolism of the endobiotics.
      Forthermore, these findings imply that xenobiotic oxidations by P450 enzymes are
      affected by endobiotic molecules and that the endobiotic-xenobiotic interactions
      as well as drug-drug interactions or drug-food/beverage interactions may be of
      great importance when understanding the basis for pharmacological and
      toxicological actions of a number of xenobiotic chemicals.

PMID- 19594412
TI  - Acronycine derivatives: a promising series of anticancer agents.
AB  - The pyranoacridone acronycine (1) exhibits antitumor properties against a large
      panel of solid tumor models, but its moderate potency and low water solubility
      severely hampered the subsequent clinical trials. Development of synthetic
      analogues followed the isolation from several Sarcomelicope species of acronycine
      epoxide (17), which led to a hypothesis of bioactivation of acronycine by
      transformation of the 1,2-double bond into the corresponding oxirane. 1,2
      Diacyloxy-1,2-dihydroacronycine derivatives exhibited antitumor properties, with
      a broadened spectrum of activity and an increased potency. The demonstration that
      acronycine interacted with DNA led to the development of benzo[a], [b], and
      [c]acronycine analogs. 1,2-Dihydroxy-1,2-dihydrobenzo[b]acronycine esters and
      diesters were active in human orthotopic models of cancers xenografted in nude
      mice. The activity of these compounds, exemplified by cis-1,2-diacetoxy-1,2
      dihydrobenzo[b]acronycine (49), developed in phase I clinical trials under the
      code S23906-1, was correlated with their ability to give covalent adducts with
      DNA, involving reaction between the N-2 amino group of guanines in the minor
      groove and the ester group at the benzylic position of the drug. The influence of
      the kinetics of DNA alkylation on the cytotoxic and antitumor properties showed a
      strong correlation between antiproliferative activity and DNA alkylation
      kinetics, with the most cytotoxic compounds, appearing as the slowest DNA
      alkylators. Hybrid compounds associating the acridone or benzo[b]acridone
      chromophore of acronycine derivatives and the epoxyfuran alkylating unit present
      in psorospermin also displayed potent antiproliferative activities, alkylating
      DNA guanine units at position N-7 in the major groove, as natural xanthones
      belonging to the psorospermin series.

PMID- 19594413
TI  - Targeting the tumor stroma with peroxisome proliferator activated receptor (PPAR)
      agonists.
AB  - Tumor cells depend on and are able to modulate the tumor stroma establishing a
      permissive and supportive environment of their own. Targeting the tumor stroma
      has evolved as a novel concept that has attracted attention of cancer researchers
      aiming at the treatment of metastatic cancer. The novel paradigm is that
      modulating the stroma will possibly not cure the cancer, but will make it a
      manageable disease for long periods of time by prohibiting the cancer from
      growing beyond a certain mass. Accordingly, in the last years, a multitude of
      stroma-targeting agents were developed comprising either classic small molecule
      drugs (e.g. sorafenib, an inhibitor of multiple tyrosine kinases) or recombinant
      antibodies (e.g. anti-VEGF) for targeting of tumor angiogenesis. Apart from these
      specifically targeted drugs, some well established drugs, primarily designed for
      non-oncologic diseases, have revealed antitumor activity on the basis of nuclear
      receptor modulation unfolding pleiotropic biological effects including stroma
      modulation. Peroxisome Proliferator Activated Receptor (PPAR) agonists,
      particularly thiazolidinedione derivatives such as pioglitazone and ciglitazone,
      are promising examples as they exert both a direct antitumoral and a broad
      spectrum of anti-stromal, antiangiogenic and immuno-modulating activities. This
      review will focus on the stroma-mediated anticancer activities of PPAR agonists.

PMID- 19594414
TI  - Differential conservation of nucleotides and conservation/mutation correlations
      between nucleotides, with special reference to CXC 1 and 4 and FP receptors
      involved in immune regulation.
AB  - Random mutations of the first nucleotide of a coding triplet alter the
      hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the
      hydrophilic amino acids, while random mutations of the second nucleotide alter
      the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of
      the hydrophilic amino acids. In cases of a change of the hydropathic character, a
      second random mutation in the previously unmutated first or second nucleotide
      causes reversion to the original character of an additional 11 % of the
      originally hydrophobic-coding triplets and an additional 14 % of the originally
      hydrophilic-coding triplets (on average). Thus, a selection oriented towards the
      preservation of the hydropathic character of amino acids may be expected to
      eventually result in a higher conservation of the second nucleotide (as compared
      to the first). In the case of uncorrected mutations of one of the two first
      nucleotides, it may be expected that appropriate second mutations in the other
      unaffected nucleotide will be positively selected. This would result in a
      positive correlation between the conservation/mutation indexes of the two first
      nucleotides, as these would be prevailingly either both conserved or both
      mutated. We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4
      and formyl peptide receptors; a group comprising different receptors of the
      rhodopsin-like superfamily, together with some viral sequences which share
      significant homologies with these receptors; a group of viral sequences with
      homologies with the rhodopsin-like receptors; a group of solute carriers. In all
      the experimental groups the second nucleotide of the triplet was the most
      conserved and a significant positive correlation existed between
      conservation/mutation indexes of the two first nucleotides. Similar
      conservation/mutation patterns could be of more general occurrence in the genome,
      as a consequence of selection processes.

PMID- 19594415
TI  - Human exposure to endocrine disruptors and breast milk.
AB  - Endocrine system is one of the most sensitive communication networks of the human
      body which influences all aspects of human health and well-being, including
      reproductive potential, cognitive functions, thyroid and metabolism, digestion
      and hormonal balance. In recent years basic laboratory research has been focused
      on the potential relationship between environmental contaminants and cellular
      endocrine function. Environmental contaminants are ubiquitous in the environment,
      alter endocrine physiology and produce endocrine disruption without acting as
      classic toxicants. These endocrine disruptors (EDCs) are lipophilic and stored
      for long periods of time in the adipose tissue. Maternal exposure to EDCs during
      pregnancy and lactation has as a result the exposure of the fetus and neonate
      through placenta and breast milk. It has been recognized that human milk is the
      best natural food for neonates providing immunologic, developmental and practical
      advantages throughout childhood. However, contamination of human milk by the
      presence of environmental toxicants is widespread through the past decades due to
      inadequately controlled pollution. Persistent pesticides, chemical solvents and
      others tend to invade slowly the environment, to bioaccumulate in the food chain
      and to have long half-lives in animals and humans. During the past fifteen years,
      the scientific interest has been focused on xenoestrogens, i.e.,environmental
      chemicals with estrogen disrupting activity. Certain adverse health and
      reproductive outcomes are attributed to these chemicals in wildlife, in
      laboratory animals, as well as in humans. Although most toxic agents are
      hazardous in high doses, the human health risks associated with EDCs concern
      exposure to low doses. The human health risks that may be associated with these
      low-level but constant exposures are still largely unknown and highly
      controversial. In this paper, we review available data on environmental chemicals
      present in breast milk that may affect child health through breastfeeding.
      Specifically, we focused on the breast-feeding pharmacokinetic aspects related to
      infant exposure of chemical pollutants that have estrogen and antiandrogen
      activities, such as environmental estrogen disruptors or xenoestrogens.

PMID- 19594416
TI  - TNF alpha inhibition as treatment modality for certain rheumatologic and
      gastrointestinal diseases.
AB  - With the development of biologicals that specifically target tumor necrosis
      factor (TNF)alpha, our therapeutic approach to inflammatory diseases has
      dramatically changed. There are currently three anti-TNFalpha drugs available:
      etanercept, infliximab, and adalimumab. Etanercept is a recombinant fusion
      protein that can be used alone or in combination with other medications for
      conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic
      arthritis, psoriasis, and ankylosing spondylitis. Infliximab, a chimeric
      humanized monoclonal antibody and adalimumab, a fully human monoclonal antibody
      are approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic
      arthritis, ankylosing spondylitis, and moderate to severe Crohn's disease.
      Infliximab is also approved for ulcerative colitis. Another anti-TNFalpha drug,
      certolizumab pegol, was declined approval as treatment option for active Crohn's
      disease due to a lack of sufficient efficacy. Phase III studies for the treatment
      of rheumatoid arthritis patients are still pending. It is the goal of this review
      article to summarize various therapeutic indications, underlying studies, safety,
      and use during pregnancy, as well as future directions for anti-TNF therapies.

PMID- 19594417
TI  - Role of iodine, selenium and other micronutrients in thyroid function and
      disorders.
AB  - Micronutrients, mostly iodine and selenium, are required for thyroid hormone
      synthesis and function. Iodine is an essential component of thyroid hormones and
      its deficiency is considered as the most common cause of preventable brain damage
      in the world. Nowadays about 800 million people are affected by iodine deficiency
      disorders that include goiter, hypothyroidism, mental retardation, and a wide
      spectrum of other growth and developmental abnormalities. Iodine supplementation,
      under form of iodized salt and iodized vegetable oil, produced dramatic
      improvements in many areas, even though iodine deficiency is still a problem not
      only for developing countries. In fact, certain subpopulations like vegetarians
      may not reach an adequate iodine intake even in countries considered iodine
      sufficient. A reduction in dietary iodine content could also be related to
      increased adherence to dietary recommendations to reduce salt intake for
      preventing hypertension. Furthermore, iodine intakes are declining in many
      countries where, after endemic goiter eradication, the lack of monitoring of
      iodine nutrition can lead to a reappearance of goiter and other iodine deficiency
      disorders. Three different selenium-dependent iodothyronine deiodinases (types I,
      II, and III) can both activate and inactivate thyroid hormones, making selenium
      an essential micronutrient for normal development, growth, and metabolism.
      Furthermore, selenium is found as selenocysteine in the catalytic center of
      enzymes protecting the thyroid from free radicals damage. In this way, selenium
      deficiency can exacerbate the effects of iodine deficiency and the same is true
      for vitamin A or iron deficiency. Substances introduced with food, such as
      thiocyanate and isoflavones or certain herbal preparations, can interfere with
      micronutrients and influence thyroid function. Aim of this paper is to review the
      role of micronutrients in thyroid function and diseases.

PMID- 19594418
TI  - Immunomodulatory and anti-inflammatory activities of statins.
AB  - The statins are a group of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase that are used extensively in medical practice because of their ability
      to reduce cardiovascular mortality and stroke. Although this protective activity
      was initially ascribed to the inhibition of cholesterol biosynthesis in the
      liver, clinical trials and basic research studies indicate that, beyond their
      cholesterol-lowering activity, statins might affect the function of different
      cell types in extrahepatic tissues. Here we will review the different mechanisms
      by which the statins exert their immunomodulatory and anti-inflammatory
      functions. We propose that statin pleiotropism is a key to the explanation of
      these activities, as it enables statins to act cooperatively in various steps of
      the inflammatory reaction, including terminal differentiation of immune cells,
      endothelial cell function, and regulation of the molecules that steer these cells
      to the sites at which they exert their immunomodulatory activity.

PMID- 19594419
TI  - Genetic alterations in differentiated thyroid cancers.
AB  - Differentiated thyroid cancers are the predominant malignancies of the thyroid.
      Due to advances in the understanding of the activation of the cell proliferation
      pathway at a molecular level, multiple genetic alterations have been linked to
      the development of thyroid carcinogenesis. Although the genetic alterations can
      be categorized into 7 categories, the BRAF mutation, RET/PTC, Pax8/PPARGamma, and
      dysfunctional Fas pathway have been most commonly described. Each of the gene
      alterations can ultimately result in cancer development, invasion and/or
      metastasis. This article provides a detailed review of the altered cell
      proliferation pathway activations found in thyroid carcinogenesis. The molecular
      targets that may be disrupted by therapeutic agents during the abnormal
      proliferation are also summarized.

PMID- 19594420
TI  - Factors modulating fibrates response: therapeutic implications and alternative
      strategies.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates
      transcription of genes involved both in lipid and glucose metabolism as well as
      in inflammation. Fibrates are PPARalpha ligands used to normalize lipid and
      glucose parameters and exert antiinflammatory effects. In fact, fibrates have
      already been demonstrated to benefit metabolic syndrome, type 2 diabetes and
      cardiovascular diseases. This article reviews the mechanism of action and the
      functional roles of fibrates, emphasizing the factors modulating their capacity
      to activate PPARalpha and affecting their effectiveness. These factors may
      possibly explain the findings obtained in animal studies and clinical trials with
      fibrates which showed either untoward effects and/or inefficient hypolipidemic
      action of PPARalpha activation. We also discuss briefly the natural and synthetic
      agonists of PPARalphawhich are currently being developed and supposedly display
      greater effectiveness and fewer adverse effects than fibrates.

PMID- 19594421
TI  - Advances in Mycobacterium tuberculosis structural genomics: investigating
      potential chinks in the armor of a deadly pathogen.
AB  - The waning effectiveness of established tuberculosis treatments due to the rise
      of multi and extensively drug-resistant strains of Mycobacterium tuberculosis,
      coupled with the synergism of HIV infection, demands basic research efforts to
      inform focused drug development programs. Structural genomics projects provide
      rich sources of information for the rational design of anti-tubercular drugs,
      aiming to exploit unique and novel protein features and interactions based on
      atomic resolution structures. This review compiles structures of M. tuberculosis
      proteins elucidated since January 2007 that are promising avenues for drug
      design, encompassing proteins involved with known and experimental
      antituberculosis drugs, metabolism, dealing with the hostile environment of the
      host organism, and information processing.

PMID- 19594423
TI  - Computational resources for protein modelling and drug discovery applications.
AB  - The design of new medications is an intensive, time-consuming and costly process.
      Over the years, a rational approach that exploits the structural knowledge of a
      biological target has led to many successes. This procedure can be expedited
      using computer-aided modelling techniques. The structure-based approach to drug
      design relies on knowing the three-dimensional structure of the target
      macromolecule. If an experimental structure has not been determined yet, a good
      approximation of the protein target structure can be obtained through
      computational modelling, provided that some structures of its homologues are
      available to serve as templates. The vast majority of drugs currently on the
      market act by disrupting the interaction between a protein and its physiological
      ligand(s). Hence, once a molecular model is available, the next step is to
      identify and study its putative ligand-binding sites. Molecular "docking" may
      then be performed in silico to predict the modes of interaction between the
      ligand and the target. In this review, a list of computational resources for
      structure-based drug design has been compiled. It is hoped that readers who do
      not have much experiences will be equipped with the appropriate tools to make a
      first attempt at protein modelling and in silico ligand docking exercises.

PMID- 19594422
TI  - Benefits of structural genomics for drug discovery research.
AB  - While three dimensional structures have long been used to search for new drug
      targets, only a fraction of new drugs coming to the market has been developed
      with the use of a structure-based drug discovery approach. However, the recent
      years have brought not only an avalanche of new macromolecular structures, but
      also significant advances in the protein structure determination methodology only
      now making their way into structure-based drug discovery. In this paper, we
      review recent developments resulting from the Structural Genomics (SG) programs,
      focusing on the methods and results most likely to improve our understanding of
      the molecular foundation of human diseases. SG programs have been around for
      almost a decade, and in that time, have contributed a significant part of the
      structural coverage of both the genomes of pathogens causing infectious diseases
      and structurally uncharacterized biological processes in general. Perhaps most
      importantly, SG programs have developed new methodology at all steps of the
      structure determination process, not only to determine new structures highly
      efficiently, but also to screen protein/ligand interactions. We describe the
      methodologies, experience and technologies developed by SG, which range from
      improvements to cloning protocols to improved procedures for crystallographic
      structure solution that may be applied in "traditional" structural biology
      laboratories particularly those performing drug discovery. We also discuss the
      conditions that must be met to convert the present high-throughput structure
      determination pipeline into a high-output structure-based drug discovery system.

PMID- 19594425
TI  - Structural biology of bacterial secretion systems in gram-negative pathogens-
      potential for new drug targets.
AB  - Gram-negative bacteria have evolved diverse secretion systems/machineries to
      translocate substrates across the cell envelope. These various machineries fulfil
      a wide variety of functions but are also essential for pathogenic bacteria to
      infect human or plant cells. Secretion systems, of which there are seven, utilize
      one of two secretion mechanisms: (i) the one-step mechanism, whereby substrates
      are translocated directly from the bacterial-cytoplasm to the extracellular
      medium or into the eukaryotic-target cell; (ii) the two-step mechanism, whereby
      substrates are first translocated across the bacterial-inner membrane; once in
      the periplasm, substrates are targeted to one of the secretion systems that
      mediate the transport across the outer membrane and the release outside the
      bacterial cell. This review describes in details the main structural features of
      these secretion systems. Structural biology offers the possibility to understand
      the molecular mechanisms at play in the various secretion systems. It also helps
      to design specifically drugs that can block these machineries and thus attenuate
      the virulence of pathogenic bacteria.

PMID- 19594426
TI  - The Seattle Structural Genomics Center for Infectious Disease (SSGCID).
AB  - The NIAID-funded Seattle Structural Genomics Center for Infectious Disease
      (SSGCID) is a consortium established to apply structural genomics approaches to
      potential drug targets from NIAID priority organisms for biodefense and emerging
      and re-emerging diseases. The mission of the SSGCID is to determine approximately
      400 protein structures over the next five years. In order to maximize biomedical
      impact, ligand-based drug-lead discovery campaigns will be pursued for a small
      number of high-impact targets. Here we review the center's target selection
      processes, which include pro-active engagement of the infectious disease research
      and drug therapy communities to identify drug targets, essential enzymes,
      virulence factors and vaccine candidates of biomedical relevance to combat
      infectious diseases. This is followed by a brief overview of the SSGCID structure
      determination pipeline and ligand screening methodology. Finally, specifics of
      our resources available to the scientific community are presented. Physical
      materials and data produced by SSGCID will be made available to the scientific
      community, with the aim that they will provide essential groundwork benefiting
      future research and drug discovery.

PMID- 19594424
TI  - Human Cytomegalovirus US28: a functionally selective chemokine binding receptor.
AB  - Chemokines are small cytokines that are part of a large family of molecules that
      bind to G-protein coupled receptors, which, as a family, are the most widely
      targeted group of molecules in the treatment of disease. Chemokines are critical
      for recruiting and activating the cells of the immune system during inflammation
      especially during viral infections. However, a number of viruses including the
      large herpes virus human cytomegalovirus (HCMV) encode mechanisms to impede the
      effects of chemokines or has gained the ability to use these molecules to its own
      advantage. The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is
      the best characterized of the four unique chemokine receptor-like molecules found
      in the HCMV genome. US28 has been studied as an important virulence factor for
      HCMV-mediated vascular disease and, more recently, in models of HCMV-associated
      malignancy. US28 is a rare multi-chemokine family binding receptor with the
      ability to bind ligands from two distinct chemokine classes. Ligand binding to
      US28 activates cell-type and ligand-specific signaling pathways leading to
      cellular migration, which is an important example of receptor functional
      selectivity. Additionally, US28 has been demonstrated to constitutively activate
      phospholipase C (PLC) and NF-kB signaling pathways. Understanding the
      structure/function relationships between US28, its ligands and intracellular
      signaling molecules will provide essential clues for effective pharmacological
      targeting of this multifunctional chemokine receptor.

PMID- 19594427
TI  - Antifungal activity of storage 2S albumins from seeds of the invasive weed
      dandelion Taraxacum officinale Wigg.
AB  - In this work, we isolated and characterized novel antifungal proteins from seeds
      of dandelion (Taraxacum officinale Wigg.). We showed that they are represented by
      five isoforms, each consisting of two disulphide-bonded large and small subunits.
      One of them, To-A1 was studied in detail, including N-terminal amino acid
      sequencing of both subunits, and shown to display sequence homology with the
      sunflower 2S albumin. Using different assays we demonstrated that dandelion 2S
      albumins possess inhibitory activity against phytopathogenic fungi and the
      oomycete Phytophtora infestans at micromolar concentrations with various isoforms
      differing in their antifungal activity. Thus, 2S albumins of dandelion seeds
      represent a novel example of storage proteins with defense functions.

PMID- 19594428
TI  - Using affinity propagation combined post-processing to cluster protein sequences.
AB  - The sizes of the protein databases are growing rapidly nowadays thus clustering
      protein sequences based only on sequence information becomes increasingly
      important. In this paper, we analyze the limitation of Affinity propagation (AP)
      algorithm when clustering a dataset generated randomly. Then we propose a post
      processing method to improve the AP algorithm. This method uses the median of the
      input similarities as the shared preference value, and then employs post
      processing phase combined mergence and reassignment strategy on the results of
      the AP algorithm. We have tested our method extensively and compared its
      performance with other five methods on several datasets of COG (Clusters of
      Orthologous Groups of proteins) database, SCOP and G-protein family. The number
      of clusters obtained for a given set of proteins approximate to the correct
      number of clusters in that set. Moreover, in our experiments, the quality of the
      clusters as quantified by F-measure was better than that of others (on average,
      9% better than BlastClust, 33% better than TribeMCL, 34% better than CLUSS, 59%
      better than Spectral clustering and 41% better than AP).

PMID- 19594429
TI  - Isolation and characterization of a novel small antifungal peptide from Bacillus
      megaterium D4 Isolated from the dung of wild plateau yak in China.
AB  - A novel small antifungal peptide-producing strain D4 was isolated from the dung
      of wild plateau yak and identified as Bacillus megaterium. The purification
      procedure of peptide consisted of acid precipitation, methanol extract and C(18)
      reverse-phase chromatography. The amino acid composition of peptide YP differed
      from those of antifungal peptides which have been reported to date. Peptide YP
      was proved to be a novel small antifungal cyclic peptide. It exhibited strong
      inhibitory activity against many phytopathogenic fungi and had a wild range of
      thermo stability and pH stability and was not susceptible to all proteases
      tested.

PMID- 19594430
TI  - Furin cleavage of bacterial expressed glutathione-S-transferase-pro-transforming
      growth factor beta1 fusion protein in vitro.
AB  - To investigate the processing of transforming growth factor beta1 (TGFbeta1) pro
      protein by furin protease we expressed a GST-pro-TGFbeta1 fusion protein in
      bacteria. Analysis of the furin digestion pattern revealed the liberation of 12.5
      kDa TGFbeta1 monomers. There was no evidence for cleavage of an alternative furin
      site within the pro-protein.

PMID- 19594431
TI  - Prediction of G-protein-coupled receptor classes in low homology using Chou's
      pseudo amino acid composition with approximate entropy and hydrophobicity
      patterns.
AB  - We use approximate entropy and hydrophobicity patterns to predict G-protein
      coupled receptors. Adaboost classifier is adopted as the prediction engine. A low
      homology dataset is used to validate the proposed method. Compared with the
      results reported, the successful rate is encouraging. The source code is written
      by Matlab.

PMID- 19594432
TI  - Interaction of the chaperone calreticulin with proteins and peptides of different
      structural classes.
AB  - The interaction of calreticulin with native and denatured forms and polypeptides
      in proteolytic digests of proteins representing structural classes of all-alpha
      helix (hemoglobin, serum albumin), all-beta-sheet (IgG) and alpha-helix + beta
      sheets (lysozyme, ovalbumin) was investigated. The binding of calreticulin to
      denatured proteins was found to depend on conformation and structural class of
      the protein. No interaction was observed with the native proteins, whereas
      binding was seen for the denatured proteins, the order of interaction being
      lysozyme = IgG > ovalbumin >> hemoglobin = serum albumin. Moreover, the
      interaction between calreticulin and the heat-denatured proteins depended on the
      temperature and time used for denaturation and the degree of proteolytic
      fragmentation. Calreticulin bound well to peptides in proteolytic digests from
      protease K or chymotrypsin treatment of lysozyme, IgG and ovalbumin but weakly or
      not at all to peptides in proteolytic digests of hemoglobin and serum albumin.
      Synthetic peptides from lysozyme and ovalbumin confirmed binding to hydrophobic
      peptides from these proteins. These results show that calreticulin has the
      ability to interact with denatured and fragmented forms of proteins with a
      preference for beta-strand structure and hydrophobicity.

PMID- 19594433
TI  - Immunization with peptide-protein conjugates: impact on benchmarking B-cell
      epitope prediction for vaccine design.
AB  - Benchmarking B-cell epitope prediction for vaccine design is meaningful if based
      on empirical reference data pertaining to cross-reactivities of antipeptide
      antibodies with native protein antigens; yet it is complicated by such data
      acquired using antibodies raised against peptide-protein conjugates, as peptide
      protein conjugation can differentially suppress antibody responses to peptide
      epitopes.

PMID- 19594434
TI  - Stationary phase expression, purification, and characterization of XorKI, a
      restriction endonuclease from Xanthomonas oryzae pv. oryzae.
AB  - An endonuclease from Xanthomonas oryzae pathovar oryzae KACC 10331, XorKI, was
      heterologously produced in Escherichia coli by applying the stationary state
      induction method. The yield was 5.4 mg of XorKI per liter of LB medium. XorKI
      existed in multiple oligomeric forms as evidenced by gel filtration
      chromatography. The specific activity of purified XorKI was 323000 units per mg.

PMID- 19594435
TI  - Mutagenesis studies of human cystathionine beta-synthase: residues important for
      heme binding and substrate interactions.
AB  - Human cystathionine beta-synthase (CBS) is a pyridoxal 5'-phosphate (PLP)
      dependent hemoprotein, which catalyzes the condensation of serine and
      homocysteine. Our mutagenesis studies suggest that Arg-266 is important to sense
      structural changes in heme-binding site, and that Gln-222 as well as Tyr-223 are
      involved in interactions with substrates.

PMID- 19594436
TI  - Iron metabolism: a promising target for antibacterial strategies.
AB  - In the fight against pathogenic and opportunistic bacteria, development and
      spreading of resistance to antibiotics is an increasing public health problem.
      The available antibacterial treatments are becoming less and less effective,
      making urgent the discovery of new active molecules. One strategy that has been
      explored to bypass the bacterial adaptation to drugs is to target the iron
      metabolism of bacteria, since iron is critical for all bacteria to grow. To date,
      three major ways have been assessed to exploit weaknesses in the bacterial iron
      metabolism: the "Trojan Horse strategy" which takes advantages of natural iron
      uptake systems to deliver antimicrobial compounds inside the cells; the use of
      iron-antagonists and iron-chelators in order to reduce iron availability and the
      inhibition of enzymatic steps of iron metabolism via chemical compounds. This
      review discusses these antibacterial strategies interfering with several levels
      of the bacterial iron metabolism, with a special emphasis on recently published
      and/or patented discoveries.

PMID- 19594439
TI  - Leptin as clinical target.
AB  - PLeptin is an adipocyte-derived hormone with pleiotropic effects on energy
      homeostasis, endocrine and reproductive functions, and immune responses. The
      multiple actions of leptin have led to the design and development of several
      leptin-based approaches to modulate the metabolic and endocrine status, to reduce
      inflammation, and to improve immune responses. Here, we review the current
      patents on leptin in different clinic applications.

PMID- 19594440
TI  - Central sympathetic outflow to skeletal muscle: the major link between non
      esterified fatty acids and elevated blood pressure?
AB  - Sympathetic nervous system activation is a hallmark of several conditions
      associated with an adverse prognosis, including hypertension and the metabolic
      syndrome. Proposed mediators of increased sympathetic drive include
      hyperinsulinaemia, leptin, NEFAs (non-esterified fatty acids), pro-inflammatory
      cytokines, baroreflex impairment and others. The role of NEFAs appears to be of
      particular importance given the increased levels observed in human obesity and
      the experimental results linking the NEFA-induced pressor response to sympathetic
      activation. Findings from human studies have yielded conflicting results with
      regards to a sympathetically mediated association between NEFAs and elevated
      arterial blood pressure. In the present issue of Clinical Science, Florian and
      Pawelczyk present some interesting results obtained from a small number of
      healthy normotensive lean volunteers who were exposed to NEFA infusion and
      cardiovascular and sympathetic monitoring using state of the art methodology that
      appears to be in support of such a link. However, several methodological and
      conceptual considerations need to be taken into account when interpreting the
      results from this study. Put into perspective, the case for a substantial
      sympathetically mediated pressor response to NEFA infusion does not appear to be
      a very strong one.

PMID- 19594442
TI  - Microbial quorum sensing: a tool or a target for antimicrobial therapy?
AB  - Inter-cell communication aided by released chemical signals when cell density
      reaches a critical concentration has been investigated for over 30 years as
      quorum sensing. Originally discovered in Gram-negative bacteria, quorum-sensing
      systems have also been studied extensively in Gram-positive bacteria and
      dimorphic fungi. Microbial communities communicating via quorum sensing employ
      various chemical signals to supervise their surrounding environment, alter
      genetic expression and gain advantage over their competitors. These signals vary
      from acylhomoserine lactones to small modified or unmodified peptides to complex
      gamma-butyrolactone molecules. The scope of this review is to give an insight
      into some of the quorum-sensing systems now known and to explore their role in
      microbial physiology and development of pathogenesis. Particular attention will
      be dedicated to the signalling molecules involved in quorum-sensing-mediated
      processes and the potential shown by some of their natural and synthetic
      analogues in the treatment of infections triggered by quorum sensing.

PMID- 19594441
TI  - A mechanism for the suppression of interleukin-1-induced nuclear factor kappaB
      activation by protein phosphatase 2Ceta-2.
AB  - IL-1 (interleukin-1) is a pro-inflammatory cytokine that has a variety of effects
      during the process of inflammation. Stimulating cells with IL-1 initiates a
      signalling cascade that includes the activation of NF-kappaB (nuclear factor
      kappaB), and subsequently induces a variety of inflammatory genes. Although the
      molecular mechanism for the IL-1-induced activation of NF-kappaB has been well
      documented, much less is known about the mechanism by which protein phosphatases
      down-regulate this pathway. Here we show that mouse PP2Ceta-2 (protein
      serine/threonine phosphatase 2Ceta-2), a novel member of the protein
      serine/threonine phosphatase 2C family, inhibits the IL-1-NF-kappaB signalling
      pathway. Ectopic expression of PP2Ceta-2 in human embryonic kidney HEK293IL-1RI
      cells inhibited the IL-1-induced activation of NF-kappaB. TAK1 (transforming
      growth-factor-beta-activated kinase 1) mediates the IL-1 signalling pathway to NF
      kappaB, and we observed that the TAK1-induced activation of NF-kappaB was
      suppressed by PP2Ceta-2 expression. Expression of IKKbeta [IkappaB (inhibitory
      kappaB) kinase beta], which lies downstream of TAK1, activates NF-kappaB, and
      this activation was also readily reversed by PP2Ceta-2 co-expression.
      Additionally, PP2Ceta-2 knockdown with small interfering RNA further stimulated
      the IL-1-enhanced phosphorylation of IKKbeta and destabilization of IkappaBalpha
      in HeLa cells. PP2Ceta-2 knockdown also increased the IL-1-induced expression of
      IL-6 mRNA. Furthermore, IKKbeta was readily dephosphorylated by PP2Ceta-2 in
      vitro. These results suggest that PP2Ceta-2 inhibits the IL-1-NF-kappaB
      signalling pathway by selectively dephosphorylating IKKbeta.

PMID- 19594443
TI  - Methods comparison for high-resolution transcriptional analysis of archival
      material on Affymetrix Plus 2.0 and Exon 1.0 microarrays.
AB  - Microarray gene expression profiling of formalin-fixed paraffin-embedded (FFPE)
      tissues is a new and evolving technique. This report compares transcript
      detection rates on Affymetrix U133 Plus 2.0 and Human Exon 1.0 ST GeneChips
      across several RNA extraction and target labeling protocols, using routinely
      collected archival FFPE samples. All RNA extraction protocols tested (Ambion
      Optimum, Ambion-RecoverAll, and Qiagen-RNeasy FFPE) provided extracts suitable
      for microarray hybridization. Compared with Affymetrix One-Cycle labeled
      extracts, NuGEN system protocols utilizing oligo(dT) and random hexamer primers,
      and cDNA target preparations instead of cRNA, achieved percent present rates up
      to 55% on Plus 2.0 arrays. Based on two paired-sample analyses, at 90%
      specificity this equalled an average 30 percentage-point increase (from 50% to
      80%) in FFPE transcript sensitivity relative to fresh frozen tissues, which we
      have assumed to have 100% sensitivity and specificity. The high content of Exon
      arrays, with multiple probe sets per exon, improved FFPE sensitivity to 92% at
      96% specificity, corresponding to an absolute increase of ~600 genes over Plus
      2.0 arrays. While larger series are needed to confirm high correspondence between
      fresh-frozen and FFPE expression patterns, these data suggest that both Plus 2.0
      and Exon arrays are suitable platforms for FFPE microarray expression analyses.

PMID- 19594444
TI  - A rapid, cost-effective method for counting human embryonic stem cell numbers as
      clumps.
AB  - Enumeration of human embryonic stem cell (hESC) numbers through single cell
      digestion can be time consuming especially in high-throughput or multi-factorial
      analysis containing 50+ samples. We have developed a reproducible, cost-effective
      method of counting hESCs in clumps circumventing the need to manually dissociate
      each sample to single cells. The method is based on the DNA binding capacity of
      propidium iodide (PI) and subsequent fluorescent signal detection. Standard
      curves generated for cell numbers versus PI fluorescence as single cells or
      clumps showed an almost identical relationship in the lines of best fit. The
      reproducibility of the assay was first demonstrated by seeding hESC clumps at
      specific cell densities ranging 0.05[#x02013]2x105 cells/well and then secondly
      by using the assay to count cell numbers after different growth conditions.
      Validation tests showed that consistent seeding densities are important in
      maintaining undifferentiated hESC culture and that the assay can be used to
      estimate relative cell numbers and growth curves with high accuracy.

PMID- 19594445
TI  - Cell-free cloning using multiply-primed rolling circle amplification with
      modified RNA primers.
AB  - The predominant method for DNA cloning is by propagation in biological hosts, but
      this method has limitations because certain sequences are difficult to clone
      using any combination of available hosts or vectors. Recently, multiply-primed
      rolling circle amplification (MPRCA) has been applied to overcome the problems of
      the DNA cloning via host cells. However, when MPRCA is used to amplify from
      minute quantities of DNA template, the products are mostly by-product DNA
      molecules generated by false priming and primer dimer formation. This study
      demonstrates that MPRCA using random RNA primers[#x02014]instead of DNA
      primers[#x02014]blocked the synthesis of by-products and succeeded in amplifying
      one copy of a circular DNA molecule more than 1012-fold to give microgram
      quantities of amplification product without using submicroliter reaction volumes.
      Furthermore, a ligation strategy was elaborated to circularize only the desired
      DNA sequence and eliminate undesired ligation-products. A combination of these
      methods was able to amplify and ligate a large construct without undesired DNA
      sequences and at microgram quantities within one day. Therefore, these methods
      have the possibility to improve DNA cloning techniques that have been restricted
      by the limitations of PCR methods or by the host cell.

PMID- 19594446
TI  - Transcriptional effects of transfection: the potential for misinterpretation of
      gene expression data generated from transiently transfected cells.
AB  - Transfection is used to introduce a gene of interest into a cell. To interpret
      the downstream results, understanding which effects are the true biological
      responses to the gene and which, if any, are off-target effects can be difficult.
      In order to discriminate true biological effects from off-target effects, we
      transfected a breast cancer cell line, MCF7, with a vector encoding either a
      reporter gene or the identical vector without the reporter gene insert. Both
      resulted in similar numbers of differentially expressed transcripts, suggesting
      that very few of the responses were directly due to the introduction of the
      reporter gene. We postulate that many differentially expressed transcripts are
      the result of the introduction of foreign DNA, as the biological processes
      associated with these genes are primarily associated with an immune response to a
      viral infection. Interestingly, different transfection reagents resulted in > 10
      fold difference in the number of differentially expressed transcripts. This
      suggests the importance of testing multiple reagents and selecting the best
      transfection reagent along with the appropriate vector within the context of the
      experimental model system to ensure that the majority of the observed responses
      are biological effects of the gene of interest and not based on a particular
      transfection process used.

PMID- 19594447
TI  - Bioluminescent CXCL12 fusion protein for cellular studies of CXCR4 and CXCR7.
AB  - Chemokine CXCL12 and its two known receptors, CXCR4 and CXCR7, may play a role in
      diseases including tumor growth and metastasis, atherosclerosis, and HIV
      infection. Therefore, these molecules may be promising targets for drug
      development. While studies of cell signaling and high-throughput screening for
      drug discovery increasingly are based on luminescent assays because of their high
      sensitivity and signal-to-background ratio, there currently is no bioluminescent
      assay for chemokine[#x02013]chemokine receptor binding. To develop a
      bioluminescent probe for chemokine binding and cellular uptake, we fused CXCL12
      to Gaussia luciferase (GL), an ATP-independent enzyme that is the smallest known
      luciferase. Fusing CXCL12 to Gaussia luciferase (CXCL12-GL) did not alter the
      bioluminescence emission spectrum and only minimally affected enzyme function
      under varying conditions of pH, temperature, and NaCl concentration. CXCL12-GL
      also activated CXCR4-dependent signaling to a comparable extent as unfused
      CXCL12. Using multiwell plate assays, we established that CXCR7 increases cell
      associated CXCL12 to a significantly greater extent than CXCR4. We also showed
      that CXCL12-GL can be used to quantify inhibition of chemokine receptor binding
      by compounds that specifically target CXCR7. These data validate CXCL12-GL as a
      bioluminescent probe to investigate molecular functions of CXCR4 and CXCR7 and
      screen for compounds that modulate ligand-receptor binding.

PMID- 19594448
TI  - An improved method for large-scale preparation of negatively and positively
      supercoiled plasmid DNA.
AB  - A rigorous understanding of the biological function of superhelical tension in
      cellular DNA requires the development of new tools and model systems for study.
      To this end, an ethidium bromide[#x02013]free method has been developed to
      prepare large quantities of either negatively or positively super-coiled plasmid
      DNA. The method is based upon the known effects of ionic strength on the
      direction of binding of DNA to an archaeal histone, rHMfB, with low and high salt
      concentrations leading to positive and negative DNA supercoiling, respectively.
      In addition to fully optimized conditions for large-scale (>500 microg)
      supercoiling reactions, the method is advantageous in that it avoids the use of
      mutagenic ethidium bromide, is applicable to chemically modified plasmid DNA
      substrates, and produces both positively and negatively supercoiled DNA using a
      single set of reagents.

PMID- 19594450
TI  - Multiplex Manager 1.0: a cross-platform computer program that plans and optimizes
      multiplex PCR.
AB  - Multiplex Manager 1.0 is a user-friendly cross-platform program that designs
      efficient combinations of existing genetic marker loci into multiplex polymerase
      chain reactions and optimizes using prior marker information. The program has the
      flexibility to solve two design problems: combining all markers into the smallest
      number of reactions, or alternatively, selecting a subset from many available
      markers to design an efficient and robust multiplex. Our program minimizes the
      number of reactions, the genetic linkage, and the difference in annealing
      temperature. At the same time it maximizes the spacing between markers, the
      heterozygosity, and the number of alleles. The final output provides easily
      interpreted and informative graphical representations of reactions, as well as
      the option of manually editing final reactions. Multiplex Manager 1.0 is freely
      available at www.multiplexmanager.com.

PMID- 19594451
TI  - Design of FRET-TaqMan probes for multiplex real-time PCR using an internal
      positive control.
AB  - The multiplexing capabilities with different fluorescent dyes are limited in real
      time PCR instruments equipped with one excitation source. Considering this
      limitation, a design was developed to create a triple-labeled probe as an
      internal positive control (IPC) that utilizes a combination of the fluorescence
      resonance energy transfer (FRET) and TaqMan techniques. The IPC probe, labeled
      with FAM and Cy5.5 fluorophores at the 5' end and Black Hole Quencher (BHQ) at
      the 3' end, enabled Cy5.5 emission through energy transfer from the FAM
      fluorophore. The second, target-specific TaqMan assay in the multiplex used a FAM
      and BHQ1-labeled probe at the 5' and 3' ends, respectively. Thus, one excitation
      source was used to generate two different fluorescence emissions (FAM and Cy5.5)
      that were measured in two separate channels by the real-time PCR instrument. This
      method can facilitate the development of a low-cost portable handheld real-time
      PCR instrument capable of multiplex real-time PCR assays using a single
      excitation source.

PMID- 19594449
TI  - Cell-free protein synthesis using multiply-primed rolling circle amplification
      products.
AB  - Utilizing in vitro transcription and translation (IVTT) to produce small
      quantities of proteins is convenient but requires a significant supply of pure
      template DNA. This can be cumbersome, particularly when the method is used for
      many different templates in a high-throughput manner. Multiply-primed rolling
      circle amplification (RCA) with [#x03C6]29 DNA polymerase is a simple way to
      generate large amounts of DNA; however, the products of this amplification method
      have interruptions in both strands and branched structures. In this study, we
      tested whether RCA-generated DNA can serve as the template for in vitro
      transcription. We found that RCA DNA[#x02013]generated transcripts work in
      coupled in vitro translation with nearly the same efficiency (per nanogram of
      DNA) as those obtained from purified plasmid. We propose a convenient, single
      tube format for template amplification, transcription, and translation.

PMID- 19594452
TI  - Site-directed mutagenesis of multi-copy-number plasmids: Red/ET recombination and
      unique restriction site elimination.
AB  - Existing methods for site-directed plasmid mutagenesis are restrained by the
      small spectrum of modifications that can be introduced by mutagenic primers and
      the amplicon size limitations of in vitro DNA synthesis. As demonstrated here,
      the combined use of Red/ET recombination and unique restriction site elimination
      enables extensive manipulation regardless of plasmid size and DNA sequence
      elements. First, a selectable marker is PCR-amplified with synthetic primers
      attaching 50-bp homology target flanks for Red/ET recombination and an arbitrary
      restriction site absent in the substrate plasmid. The resulting cassette is co
      electroporated with substrate plasmids in Red/ET-proficient Escherichia coli
      cells. Following isolation of recombinant plasmids, linear nonselectable DNA
      replaces the cassette and introduces the desired mutation(s) in a second Red/ET
      recombination step. Upon selective digestion of parental plasmids and
      retransformation, a 38% mutation efficiency was achieved using a synthetic 97
      nucleotide oligonucleotide to cure a 17-bp deletion within lacZalpha of pUC19
      (2,686 bp). A PCR fragment was used with similar efficiency to co-replace mouse
      Cdkn1b codons 9 and 76 in gene-targeting vector pGTC (13,083 bp).

PMID- 19594453
TI  - Transposon-directed base-exchange mutagenesis (TDEM): a novel method for multiple
      nucleotide substitutions within a target gene.
AB  - In this report we describe transposon-directed base-exchange mutagenesis (TDEM),
      an efficient and controllable method for introducing a mutation into a gene. Each
      round of TDEM can remove up to 11 base pairs from a randomly selected site within
      the target gene and replace them with any length of DNA of predetermined
      sequence. Therefore, the number of bases to be deleted and inserted can be
      independently regulated providing greater versatility than existing methods of
      transposon-based mutagenesis. Subsequently, multiple rounds of mutagenesis will
      provide a diverse mutant library that contains multiple mutations throughout the
      gene. Additionally, we developed a simple frame-checking procedure that
      eliminates nonfunctional mutants containing frameshifts or stop codons. As a
      proof of principle, we used TDEM to generate mutant lacZalpha lacking alpha
      complementation activity and recovered active revertants using a second round of
      TDEM. Furthermore, a single round of TDEM yielded unique, inactive mutants of
      ccdB.

PMID- 19594454
TI  - Simple non-fluorescent polarity labeling of microtubules for molecular motor
      assays.
AB  - Transport of intracellular organelles along the microtubule cytoskeleton occurs
      in a bidirectional manner due to opposing activity of microtubule-associated
      motor proteins of the kinesin and dynein families. Regulation of this opposing
      activity and the resultant motion is believed to generate a polarized
      distribution of many organelles within the cell. The bidirectional motion can be
      reconstituted on in vitro assembled microtubules using organelles extracted from
      cells. This provides an opportunity to understand the regulation of intracellular
      transport through quantitative analysis of the motion of organelles in a
      controlled environment. Such analysis requires the use of polarity-labeled
      microtubules to resolve the plus and minus components of bidirectional motion.
      However, existing methods of in vitro microtubule polarity labeling are
      unsuitable for high-resolution recording of motion. Here we present a simple and
      reliable method that uses avidin-coated magnetic beads to prepare microtubules
      labeled at the minus end. The microtubule polarity can be identified without any
      need for fluorescence excitation. We demonstrate video-rate high-resolution
      imaging of single cellular organelles moving along plus and minus directions on
      labeled microtubules. Quantitative analysis of this motion indicates that these
      organelles are likely to be driven by multiple dynein motors in vivo.

PMID- 19594455
TI  - Mouse embryo cryopreservation utilizing a novel high-capacity vitrification
      spatula.
AB  - Embryo cryopreservation is an indispensable technique in reproductive programs
      and in animal facilities where genetically modified mice are used extensively.
      Here we report the use of a vitrification spatula (VS) that can be readily
      homemade and has a large holding capacity to vitrify preimplantation mammalian
      embryos in a micro-drop employing ultra-rapid cooling in liquid nitrogen (LN2).
      Vitrified one-cell embryos and morulae have high survival rates after thawing,
      and the fertility of the derived progeny is comparable to that of the control
      unvitrified group. The large holding capacity (up to 50 embryos per VS) does not
      only allow rapid expansion of storage capacity for additional mouse strains but
      also opens up the possibility to streamline transgenic mice generation procedures
      in transgenic facilities.

PMID- 19594456
TI  - A device for automated hydrodynamic shearing of genomic DNA.
AB  - We describe a device for automated fragmentation of genomic DNA by hydrodynamic
      shearing using a filter screen with uniform pores. Human genomic DNA can be
      fragmented reproducibly to a range of 2000-12,000 bp by using various fluid flow
      rates and screens with 0.5-10-microm pores. The utilization of disposable screens
      eliminates sample cross-contamination and the tendency of device clogging,
      commonly encountered in single-orifice shearing devices.

PMID- 19594457
TI  - Can there be truth about TASERs?

PMID- 19594458
TI  - Risk factors for mortality of bacteremic patients in the emergency department.
AB  - OBJECTIVES: Patients with bacteremia have a high mortality and generally require
      urgent treatment. The authors conducted a study to describe bacteremic patients
      in emergency departments (EDs) and to identify risk factors for mortality.
      METHODS: Bacteremic patients in EDs were identified retrospectively at a
      university hospital from January 2007 to December 2007. Demographic
      characteristics, underlying illness, clinical conditions, microbiology, and the
      source of bacteremia were collected and analyzed for their association with 28
      day mortality. RESULTS: During the study period, 621 cases (50.2% male) were
      included, with a mean (+/-SD) age of 62.8 (+/-17.4) years. The most common
      underlying disease was diabetes mellitus (39.3%). Escherichia coli (39.2%) was
      the most frequently isolated pathogen. The most common source of bacteremia was
      urinary tract infection (41.2%), followed by primary bacteremia (13.2%). The
      overall 28-day mortality rate was 12.6%. Multivariate stepwise logistic
      regression analysis showed age > 60 years (odds ratio [OR] = 2.52, 95% confidence
      interval [CI] = 1.29 to 4.92, p = 0.007), malignancy (OR = 2.66, 95% CI = 1.44 to
      4.91, p = 0.002), liver cirrhosis (OR = 2.08, 95% CI = 1.02 to 4.26, p = 0.044),
      alcohol use (OR = 5.73, 95% CI = 2.10 to 15.63, p = 0.001), polymicrobial
      bacteremia (OR = 3.99, 95% CI = 1.75 to 9.10, p = 0.001), anemia (OR = 2.33, 95%
      CI = 1.34 to 4.03, p = 0.003), and sepsis (OR = 1.94, 95% CI = 1.16 to 3.37, p =
      0.019) were independent risk factors for 28-day mortality. CONCLUSIONS:
      Bacteremic patients in the ED have a high mortality, particularly with these risk
      factors. It is important for physicians to recognize the factors that potentially
      contribute to mortality of bacteremic patients in the ED.

PMID- 19594459
TI  - A review of the federal guidelines that inform and influence relationships
      between physicians and industry.
AB  - The effective delivery and continued advancement of health care is critically
      dependent on the relationship between physicians and industry. The private sector
      accounts for 60% of the funding for clinical research and more than 50% of the
      funding sources for physician education. The nature of the physician-industry
      relationship and the role of the physician as a gatekeeper for health care make
      this association vulnerable to abuse if certain safeguards are not observed. This
      article will review the current federal guidelines that affect the physician
      industry relationship and highlight several illustrative cases to show how the
      potential for abuse can subvert this relationship. The recommendations and "safe
      harbors" that have been designed to guide business relationships in health care
      are discussed.

PMID- 19594460
TI  - One-year outcomes following coronary computerized tomographic angiography for
      evaluation of emergency department patients with potential acute coronary
      syndrome.
AB  - OBJECTIVES: Coronary computerized tomographic angiography (CTA) has high
      correlation with cardiac catheterization and has been shown to be safe and cost
      effective when used for rapid evaluation of low-risk chest pain patients from the
      emergency department (ED). The long-term outcome of patients discharged from the
      ED with negative coronary CTA has not been well studied. METHODS: The authors
      prospectively evaluated consecutive low- to intermediate-risk patients who
      received coronary CTA in the ED for evaluation of a potential acute coronary
      syndrome (ACS). Patients with cocaine use, known cancer, and significant
      comorbidity reducing life expectancy and those found to have significant disease
      (stenosis > or = 50% or ejection fraction < 30%) were excluded. Demographics,
      medical and cardiac history, labs, and electrocardiogram (ECG) results were
      collected. Patients were followed by telephone contact and record review for 1
      year. The main outcome was 1-year cardiovascular death or nonfatal acute
      myocardial infarction (AMI). RESULTS: Of 588 patients who received coronary CTA
      in the ED, 481 met study criteria. They had a mean (+/-SD) age of 46.1 (+/-8.8)
      years, 63% were black or African American, and 60% were female. There were 53
      patients (11%) rehospitalized and 51 patients (11%) who received further
      diagnostic testing (stress or catheterization) over the subsequent year. There
      was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear
      etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures
      (0%; 95% CI = 0 to 0.76%) during this time period. CONCLUSIONS: Low- to
      intermediate-risk patients with a Thrombosis In Myocardial Infarction (TIMI)
      score of 0 to 2 who present to the ED with potential ACS and have a negative
      coronary CTA have a very low likelihood of cardiovascular events over the ensuing
      year.

PMID- 19594461
TI  - Physiologic effects of the TASER after exercise.
AB  - OBJECTIVES: Incidents of sudden death following TASER exposure are poorly
      studied, and substantive links between TASER exposure and sudden death are
      minimal. The authors studied the effects of a single TASER exposure on markers of
      physiologic stress in humans. METHODS: This prospective, controlled study
      evaluated the effects of a TASER exposure on healthy police volunteers after
      vigorous exercise, compared to a subsequent, identical exercise session that was
      not followed by TASER exposure. Subjects exercised to 85% of predicted heart rate
      (HR) on an ergometer and then were given a standard 5-second TASER activation.
      Measures before and for 60 minutes after the TASER activation included minute
      ventilation, tidal volume, respiratory rate, end-tidal pCO(2), oxygen saturation,
      HR, blood pressure (systolic BP/diastolic BP), 12-lead electrocardiogram, and
      arterialized blood for pH, pO(2), pCO(2), and lactate. Each subject repeated the
      exercise and data collection session on a subsequent data, without TASER
      activation. Data were analyzed using paired Student's t-tests with differences
      and 95% confidence intervals (CIs). Statistical significance was adjusted for
      multiple comparisons. RESULTS: A total of 25 officers (21 men and 4 women)
      completed both portions of the study. After adjusting for multiple comparisons,
      the TASER group was significantly higher for systolic BP at baseline (difference
      of 14.1, 95% CI = 8.7 to 19.5, p < 0.001) and HR at 5, 30, and 60 minutes with
      the largest difference at 30 minutes (difference of 7.0, 95% CI = 2.5 to 11.5, p
      = 0.004). There were no other significant differences between the two groups in
      any other measure at any time. CONCLUSIONS: A 5-second exposure of a TASER
      following vigorous exercise to healthy law enforcement personnel does not result
      in clinically significant changes in ventilatory or blood parameters of
      physiologic stress.

PMID- 19594462
TI  - Ultrasound guided pericardiocentesis of cardiac tamponade.

PMID- 19594463
TI  - Childhood stroke in Eastern Province, KSA: pattern, risk factors, diagnosis and
      outcome.
AB  - BACKGROUND AND PURPOSE: Stroke has been increasingly recognized in children in
      recent years, but diagnosis and management can be difficult because of the
      diversity of underlying risk factors, atypical presentation and the absence of a
      uniform treatment approach. The aim of this study was to examine risk factors,
      clinical presentation, imaging findings and outcomes of paediatric stroke in
      Eastern Province, Kingdom of Saudi Arabia (KSA). SUBJECTS AND METHODS: We
      evaluated 25 patients (11 boys and 14 girls) using computerized tomography scan
      of the brain, magnetic resonance (MR) imaging and MR angiography. Cardiac
      assessment, haematological tests, immunological tests, infection and metabolic
      screening were also performed in the patients. After discharge, the patients were
      monitored regularly in the neurology clinic to detect their outcomes. RESULTS: A
      total of 76% of the patients presented with ischaemic stroke, while the remaining
      24% had haemorrhagic stroke. Sickle cell disease (SCD) was the commonest risk
      factor for stroke (36%) followed by non determinate causes (20%). Seizure was the
      commonest clinical presentation (54%) followed by haemiplegia (31%) and decreased
      level of consciousness (30%). Recurrence occurred in SCD patients (80%) and
      patients with moyamoya disease (20%). Regarding the outcome, long-term deficit
      was the commonest (44%), while short-term deficit and death were equal (28%
      each). CONCLUSION: Our study in Eastern Province, KSA, showed agreement with
      other studies regarding risk factors, clinical presentation, imaging features and
      outcomes of stroke in children, yet with some points of differences, which are as
      follows: (1) SCD is the commonest risk factor in our study population, while in
      Chinese study it was not, (2) The percentage of cardiac disorders as a risk
      factor in this study was less than that in the European and American studies, and
      (3) there was relative discrepancy regarding predictors of outcome.

PMID- 19594464
TI  - Classification, incidence and survival analyses of children with CNS tumours
      diagnosed in Sweden 1984-2005.
AB  - AIM: Primary tumours in the central nervous system (CNS) are the second most
      common malignancy in childhood after leukaemia. Sweden has a high incidence and a
      high-survival rate in international comparative studies. This has raised the
      question about the type of tumours included in the Swedish Cancer registry. We
      therefore compared international data to the Swedish Childhood Cancer registry.
      METHODS: Central nervous system tumours registered in the Swedish Childhood
      Cancer Registry were reclassified according to ICCC-3. Incidence and survival
      analyses were performed in the study population. RESULTS: There were 1479
      children (<15 years) in Sweden diagnosed with CNS tumours 1984-2005. The
      distribution of diagnoses was similar to that reported in other studies. The
      annual incidence was 4.2/100,000 children. The survival rates have not improved
      significantly between the two time periods before/after 1995 (70% vs. 74%; p =
      0.10). CONCLUSIONS: The mean annual incidence of children with CNS tumours was
      4.2/100,000 and has not increased during the study period. Survival rate for
      brain tumours at 10 years follow-up was 72%.

PMID- 19594465
TI  - Interscalene block using ultrasound guidance: impact of experience on resident
      performance.
AB  - BACKGROUND: We evaluated the weekly progress of anesthesiology residents
      performing an interscalene block with ultrasound guidance (UG) for block success
      rates and for the specific time intervals: (i) time to image the brachial plexus
      and (ii) time from insertion of the block needle until motor stimulation
      occurred. Our primary objective was to characterize the influence of experience
      over the course of the regional anesthesia rotation on the performance of a UG
      interscalene block by anesthesiology residents. METHODS: Residents conducted an
      interscalene block with UG under the supervision of attending anesthesiologists
      experienced in this technique. Block efficacy, time intervals required to perform
      the block, and acute complications were recorded. We compared success rates over
      the course of the rotation, and analyzed process time data with respect to
      trainee level of experience, week of the trainee rotation, and patient body
      habitus. RESULTS: Twenty-one trainees conducted 222 blocks over a consecutive 7
      month period. Block success rate was 97.3%, and did not change significantly over
      the course of the 4-week rotation. Total block time and imaging time
      significantly decreased over the 4-week rotation, while the needle insertion-to
      stimulation time did not change. Slower imaging time was predicted by obesity.
      CONCLUSION: The success rates for a UG interscalene block provided by supervised
      residents were initially high, and remained so throughout the 4-week rotation.
      Trainees required less time to image the nerves and to perform the block over the
      course of the rotation.

PMID- 19594467
TI  - Life-threatening hypokalemia in an infant (Case Presentation).

PMID- 19594468
TI  - A child with syncope (Case Presentation).

PMID- 19594469
TI  - Anti-inflammatory treatment of asthma: differentiation and trial-and-error.
AB  - The relative lack of evidence for anti-inflammatory treatment of some phenotypes
      of asthma in children has been highlighted in recent guidelines and consensus
      reports specifically aiming at the paediatric population. Consequently, we are
      left with a need for defining treatment strategies in the clinical setting. The
      decision to initiate antiinflammatory treatment should be based on assessments of
      the individual child's age, the type of asthma, severity, heredity and atopic
      condition, adherence factors and sensitivity to systemic adverse effects of
      treatment options. Inhaled corticosteroids are potent anti-inflammatory agents
      that are effective in the whole spectrum of asthma in school age children. In
      toddlers with viral wheeze and in children with mild asthma oral leukotriene
      receptor antagonists or inhaled corticosteroids may be given on a trial-and-error
      basis. CONCLUSION: To treat all children with asthma equally effectively from
      infancy through adolescence does not mean that they should be treated identically
      and in some types of asthma a trial-and-error approach may be warranted.

PMID- 19594470
TI  - Translating medical knowledge into practice: improving health care.

PMID- 19594471
TI  - Breastfeeding is an essential complement to vaccination.
AB  - AIM: This article explores the role of breastfeeding in different aspects of
      vaccination in the first 6 months when infants are still developing: (1) pain
      management; (2) immunomodulation of infants' vaccine responses; (3) metabolism of
      thimerosal. METHODS: Major databases were searched for studies that addressed
      outcomes of related issues. RESULTS: Studies reveal that breastfeeding can: (1)
      help mothers and infants to cope with the stressful situations that accompany
      parenteral vaccines; (2) improve response to vaccines in the still maturing
      immunologic and enterohepatic systems of infants; (3) influence physiologic
      parameters that can change metabolism of ethylmercury derived from some vaccines.
      CONCLUSION: Health promotion that supports vaccinations should also emphasize
      early initiation and maintenance of exclusive breastfeeding up until 6 months for
      maximum protection of the infants with a possible beneficial effect on the
      vaccine response. Paediatric professionals should inform mothers of the proven
      benefits of breastfeeding and its importance in complementing vaccination and
      lowering stress and the risk of untoward reactions on susceptible infants.

PMID- 19594472
TI  - Genetic testing in global developmental delay: the well-intended clinician and
      the principle of double effect.

PMID- 19594473
TI  - Knowledge and practical performance gained by Iraqi residents after participation
      to a neonatal resuscitation program course.
AB  - AIM: Neonatal resuscitation program (NRP) course is effective in improving
      knowledge in participants coming from developed as well as developing countries;
      however, its impact on practical performances has not been yet formally evaluated
      in participants coming from developing countries. We evaluate the knowledge and
      the performance on clinical simulations gained by Iraqi residents following
      participation in the NRP course. METHODS: A 71-item questionnaire derived from
      the standard test contained in the American Heart Association and American
      Academy of Pediatrics Neonatal Resuscitation Manual was administered to
      participants before and after the course. All participants were tested with a
      final Mega code (Mega code A scenario-NRP textbook) to evaluate their performance
      on clinical simulations. RESULTS: Twenty-six obstetrical and 2 pediatric
      residents participated in the NRP course, respectively. The percentages of
      correct answers significantly improved from before (52 +/- 14%) to immediately
      after the course (85 +/- 7%); p < 0.001. Mean score obtained at the final Mega
      code was 68 +/- 8%. Four out of 28 (14%) participants reached the minimum score
      required for passing the exam (80%). CONCLUSION: Residents coming from a
      developing country (Iraq) significantly improved their knowledge attainment
      following participation in the NRP course; however, their performance on clinical
      simulations was unsatisfactory, suggesting that this aspect needs to be improved.

PMID- 19594474
TI  - Altered body composition in preterm infants at hospital discharge.
AB  - AIM: To test the hypotheses that body size is reduced and body composition
      altered in preterm infants at hospital discharge. METHODS: Preterm infants (< or
      = 34 weeks gestation, < or = 1750 g at birth) were enrolled. Body weight, length
      and head circumference were converted to standard deviation or z-scores. Body
      composition was measured using dual emission X-ray absorptiometry. The results
      were analysed using standard statistics. RESULTS: One hundred and forty-nine
      infants (birth weight = 1406 +/- 248 g, gestation = 31 +/- 1.7 weeks) were
      studied. Postmenstrual age at discharge was 37 +/- 1.2 weeks. Z-scores for head
      circumference, weight and length differed (-0.1 +/- 0.6 > -1.4 +/- 0.6 > -1.9 +/-
      0.6; p < 0.0001). Global fat-free mass was less in study infants than the
      reference infant at the same weight (2062 < 2252 g; p < 0.0001) or gestation
      (2062 < 2667 g; p < 0.0001). Global fat mass was greater in study infants than
      the reference infant at the same weight (307 > 198 g, 13 > 8%) or gestation (307
      > 273 g; 13 > 9%; p < 0.0001). Changes in central fat mass closely paralleled
      those in global fat mass (r(2) = 0.76, p < 0.0001). CONCLUSION: Reduced linear
      growth and a reduced fat-free mass suggest that dietary protein needs were not
      met before discharge. A reduced fat-free mass coupled with an increased global
      and central fat mass echoes concerns about the development of insulin resistance
      and metabolic syndrome X in these high-risk infants.

PMID- 19594475
TI  - Regional differences in maturation of germ cells of cryptorchid testes: role of
      environment.
AB  - OBJECTIVE: To investigate differences in maturation of germ cells in cryptorchid
      testes in three different regions. PATIENTS AND METHODS: A total of 103
      consecutive patients were operated for unilateral undescended testis in
      Vojvodina, from March 2006 until September 2007, and had a testicular biopsy
      performed. Germ cells were counted, and the presence of Ad spermatogonia was
      noted. Biopsies were compared to biopsies of similar patients from two different
      regions: Philadelphia, USA (130), and Liestal, Switzerland (55 patients).
      RESULTS: In Vojvodina, 84.5% of patients had Sertoli cells only, or some
      spermatogonia, but no Ad spermatogonia, and 15.5% had Ad spermatogonia. In
      Philadelphia, 59.3% of patients had poor testicular histology, and 40.7% had Ad
      spermatogonia. In Liestal, 61.8% of patients had no, or some, spermatogonia, but
      no Ad spermatogonia, and 38.2% had Ad spermatogonia. There was a difference (p =
      0.000025) between the patients with normal testicular histology from Philadelphia
      and those from Vojvodina, as well as between the patients from Vojvodina and
      Liestal (p = 0.0027). CONCLUSION: The reduction in the number of germ cells in
      patients with cryptorchidism from Vojvodina is more pronounced than patients from
      either Switzerland or USA. This is a unique observation, since such a study has
      not been published yet.

PMID- 19594476
TI  - Maternal plasma 25-hydroxyvitamin D concentration and birthweight, growth and
      bone mineral accretion of Gambian infants.

PMID- 19594480
TI  - Law 180 after 30 years - reflections on unmet needs and risks of loss of identity
      for Italian psychiatrists.

PMID- 19594481
TI  - Do the old psychostimulant drugs have a role in managing treatment-resistant
      depression?
AB  - OBJECTIVE: As the authors have observed clinical benefit from the
      psychostimulants methylphenidate and dexamphetamine for treating resistant
      melancholic and bipolar depression, those drugs were evaluated in a consecutively
      recruited sample of 50 such patients. METHOD: Patients (27 bipolar, 23 unipolar)
      received either methylphenidate (n = 44) or dexamphetamine (n = 6), with 30
      having it prescribed as an augmenting drug and 20 as monotherapy. At the final
      review, ranging from 6 weeks to 62 months (mean 57 weeks), 52% were still
      receiving their psychostimulant. RESULTS: Thirty-four per cent reported the
      psychostimulant as distinctly improving their depression, 30% reported some level
      of improvement and 36% reported no improvement and/or side-effects. For
      improvers, the modal dose of methylphenidate was 20 mg. Significant side-effects
      were reported by 18% (including one manic response), switching was rare and
      limited to the bipolar subjects, and most side-effects were minor. Any positive
      response occurred rapidly and loss of efficacy was rare. Testing of tricyclic
      levels in some patients suggested that stimulant drugs may raise tricyclic levels
      in those who are rapid metabolizers. CONCLUSION: Although this study was not
      controlled, the high success rate in a diagnostically refined sample implies that
      the psychostimulants may be efficacious for patients with melancholic and bipolar
      depression who have failed to respond to orthodox antidepressant drugs.

PMID- 19594482
TI  - Birth-cohort and dual diagnosis effects on age-at-onset in Brazilian patients
      with bipolar I disorder.
AB  - OBJECTIVE: Substance use disorders and birth-cohort have been associated with an
      earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter
      relations of these factors in age-at-onset in bipolar illness. METHOD: Two
      hundred and thirty patients with bipolar I disorder were cross-sectionally
      evaluated. Patients were categorized into four age groups for analysis. Lifetime
      comorbidity and age-at-onset were derived from the Structured Clinical Interview
      for DSM-IV. RESULTS: There was a strong linear association between age group and
      age-at-onset. Lifetime alcohol and drug use disorders were also associated with
      age-at-onset. Illicit drug and alcohol use disorders and age group remained
      significant in the multivariate model. No interactions appeared. CONCLUSION: Both
      age group and dual diagnoses had strong and independent impacts on age-at-onset
      in out-patients with BD. Substance abuse may be partly accountable for earlier
      symptom onset, but other features of BD in younger generations are still in need
      to be accounted for.

PMID- 19594483
TI  - Excess use of coercive measures in psychiatry among migrants compared with native
      Danes.
AB  - OBJECTIVE: To investigate differences in risk of compulsory admission and other
      coercive measures in psychiatric emergencies among refugees and immigrants
      compared with that among native Danes. METHOD: A register-based retrospective
      cohort design. All refugees (n = 29 174) and immigrants (n = 33 287) who received
      residence permission in Denmark from 1.1.1993 to 31.12.1999 were included and
      matched 1 : 4 on age and sex with native Danes. Civil registration numbers were
      cross-linked to the Danish Psychiatric Central Register and the Registry of
      Coercive Measures in Psychiatric Treatment. RESULTS: Refugees (RR = 1.82; 95%CI:
      1.45; 2.29) and immigrants (RR = 1.14; 95%CI: 0.83; 1.56) experienced higher
      rates of compulsory admissions than did native Danes. This was most striking for
      refugee men (RR = 2.00; 95%CI: 1.53; 2.61) and immigrant women (RR = 1.73; 95%CI:
      1.45; 2.60). Moreover, refugees and immigrants experienced higher frequencies of
      other coercive measures during hospitalisation compared with native Danes.
      CONCLUSION: Coercive measures in psychiatry are more likely to be experienced by
      migrants than by native Danes.

PMID- 19594484
TI  - d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging
      in Drosophila.
AB  - dTOR (target of rapamycin) and dFoxo respond to changes in the nutritional
      environment to induce a broad range of responses in multiple tissue types. Both
      dTOR and dFoxo have been demonstrated to control the rate of age-related decline
      in cardiac function. Here, we show that the Eif4e-binding protein (d4eBP) is
      sufficient to protect long-term cardiac function against age-related decline and
      that up-regulation of dEif4e is sufficient to recapitulate the effects of high
      dTOR or insulin signaling. We also provide evidence that d4eBP acts tissue
      autonomously and downstream of dTOR and dFoxo in the myocardium, where it
      enhances cardiac stress resistance and maintains normal heart rate and myogenic
      rhythm. Another effector of dTOR and insulin signaling, dS6K, may influence
      cardiac aging nonautonomously through its activity in the insulin-producing
      cells, possibly by regulating dilp2 expression. Thus, elevating d4eBP activity in
      cardiac tissue represents an effective organ-specific means for slowing or
      reversing cardiac functional changes brought about by normal aging.

PMID- 19594485
TI  - Calorie restriction alters mitochondrial protein acetylation.
AB  - Calorie restriction (CR) increases lifespan in organisms ranging from budding
      yeast through mammals. Mitochondrial adaptation represents a key component of the
      response to CR. Molecular mechanisms underlying this adaptation are largely
      unknown. Here we show that lysine acetylation of mitochondrial proteins is
      altered during CR in a tissue-specific fashion. Via large-scale mass spectrometry
      screening, we identify 72 candidate proteins involved in a variety of metabolic
      pathways with altered acetylation during CR. Mitochondrial acetylation changes
      may play an important role in the pro-longevity CR response.

PMID- 19594486
TI  - Prescription rates of protective co-therapy for NSAID users at high GI risk and
      results of attempts to improve adherence to guidelines.
AB  - BACKGROUND: Protective co-therapy is recommended in NSAID users with GI risk
      factors, but adherence is poor. AIM: To assess the proportion of NSAID users
      receiving co-therapy and strategies to improve adherence. METHODS: Arthritis
      patients > or =50 years of age received etoricoxib or diclofenac in a double
      blind randomized trial. Reminders that high-risk patients (age > or = 65;
      previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should
      receive co-therapy were given at study initiation. Free PPI was provided. An
      intervention midway through the study included a written reminder and required
      written response regarding co-therapy. RESULTS: 16,244/23,504 (69%) patients had
      GI risk factors. Pre-intervention, co-therapy was most common with previous
      ulcer/haemorrhage [706/1107 (64%)] and 3-4 risk factors [331/519 (64%)]. In the
      10,026 patients enrolled pre-intervention and remaining in the study > or =6
      months after, co-therapy in high-risk patients increased from 2958/6843 (43%) to
      4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater
      outside the US (22%; 19%,24%) than in the US (15%; 13%,17%). CONCLUSIONS: Less
      than 50% of NSAID users with GI risk factors are given protective co-therapy-
      even if prescribers are given reminders and cost is not an issue. Direct
      communication requiring written response significantly increased adherence to
      guidelines, but achieving higher levels of adherence will require additional
      strategies.

PMID- 19594487
TI  - CXC and CC chemokines induced in human renal epithelial cells by inflammatory
      cytokines.
AB  - Human renal epithelial cells might play an important role during the allograft
      rejection by producing chemokines in response to proinflammatory cytokines such
      as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta produced by
      endothelial and epithelial cells early after transplantation. The production of
      chemokines allows inflammatory cells to be drawn into the kidney graft and
      therefore plays a critical role in the pathophysiologic processes that lead to
      the rejection of renal transplant. In this process, two chemokine superfamilies,
      the CC and the CXC chemokines, are the most important. The CC chemokines target
      mainly monocytes and T lymphocytes, while most of the CXC chemokines attract
      neutrophils. We showed in our study that in vitro, in unstimulated cells, basal
      mRNA expression of CXC chemokines (Groalpha, Grobeta, Grogamma, ENA-78 and GCP-2,
      IL-8) that attract neutrophils was detectable and expression of these genes and
      chemokine release were increased in TNF-alpha- and IL-1beta-induced renal
      epithelial cells. Most of the CC chemokines [monocyte chemotactic protein-1 (MCP
      1), macrophage Inflammatory protein 1 beta (MIP-1beta), regulated upon
      activation, normal T cell expressed and secreted (RANTES) and macrophage
      inflammatory protein (MIP-3alpha)] showed detectable mRNA expression only after
      stimulation with proinflammatory cytokines and not in control cells. TNF-alpha
      seems to induce preferably the expression of RANTES, MCP-1, interferon-inducible
      protein (IP-10) and Interferon-Inducible T-cell Alpha Chemoattractant (I-TAC),
      while IL-1beta induces mainly IL-8 and epithelial neutrophil-activating peptide
      78 (ENA-78).

PMID- 19594488
TI  - An outbreak of pneumonia associated with S. pneumoniae at a military training
      facility in Finland in 2006.
AB  - Streptococcus pneumoniae is a well-known cause of community-acquired bacterial
      pneumonia. The purpose of this study was to assess the cause and extent of the
      outbreak of pneumonia which occurred among military recruits following a 1-week
      hard encampment in Finland. We also assessed the carriage rate and molecular
      characteristics of the S. pneumoniae isolates. All pneumococcal isolates were
      studied for antibiotic susceptibility, serotyped, genotyped by multilocus
      sequence typing (MLST), and the presence of pneumococcal rlrA pilus islet was
      detected. The genotype results defined by MLST corresponded with the serotype
      results. S. pneumoniae serotype 7F, ST2331, seemed to be associated with an
      outbreak of pneumonia and nasopharyngeal carriage among 43 military recruits. Of
      the 43 military recruits, five (12%) were hospitalized with pneumonia and two
      (40%) of them were positive for S. pneumoniae serotype 7F, ST2331 by blood
      culture. Eighteen (42%) of the 43 men were found to be positive for S. pneumoniae
      by nasopharyngeal culture, and nine (50%) of them carried pneumococcal serotype
      7F, ST2331. The outbreak strain covered 55% of all the pneumococcal findings.
      Outbreaks of invasive pneumococcal disease seem to occur in a crowded environment
      such as a military training facility even among previously healthy young men.

PMID- 19594489
TI  - Role of acetylation and charge in antimicrobial peptides based on human beta
      defensin-3.
AB  - Cationic antimicrobial peptides are an evolutionarily ancient and essential
      element of innate immunity in higher organisms. The precise mechanism by which
      these peptides exert their antimicrobial activity on bacteria is not well
      understood. Decapeptides based on the C-terminus of human beta-defensin-3 were
      designed and evaluated to study the role of charge in defining the antimicrobial
      activity and selectivity of these peptides against Escherichia coli. Acetylated
      derivatives of these peptides were prepared in order to further evaluate how
      positively charged primary amines contribute to potency in these small
      antimicrobial peptides. These peptides enabled us to explore the relationship
      between net charge, charge distribution and antimicrobial activity. While the
      results indicate that net charge is a major factor in antimicrobial activity in
      these peptides, the actual relationship between charge and potency appears to be
      more complex.

PMID- 19594490
TI  - Cyclooxygenase-2 immunoreactivity in collagenous colitis.
AB  - Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology
      and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may
      be involved in the pathogenesis of inflammation, and increased expression of
      cyclo-oxygenase-2 (COX-2) has been detected. The purpose of this study was to
      examine the presence and cellular localization of COX-2 in colonic mucosa of
      patients with CC. Using immunohistochemistry, immunoflouresence and Western blot
      analysis, COX-2 expression was evaluated in colonic mucosal biopsies from 10
      patients with active untreated CC, and compared with samples from eight normal
      controls, and samples from eight patients with ulcerative colitis or Crohn's
      disease. Specimens from patients with CC expressed COX-2 protein in increased
      amounts compared with controls, but similar to patients with ulcerative colitis
      and Crohn's disease. COX-2 expression was localized to the mononuclear cells of
      the lamina propria. COX-2 expression was most evident in macrophages. Co
      localization of COX-2 and macrophages was increased in number in comparison with
      controls. In conclusion COX-2 is expressed in increased amounts primarily in the
      macrophage subpopulation of the inflammatory infiltrate of lamina propria in CC.
      Increased recruitment of macrophages, increased expression of COX-2 and increased
      prostaglandin synthesis may be involved in the pathogenesis of CC.

PMID- 19594491
TI  - Combined cell wall polysaccharide, mycotoxin and bacterial lipopolysaccharide
      exposure and inflammatory cytokine responses.
AB  - Human exposure to environmental microbes occurs regularly. Microbial compounds
      may interact with each other to affect cellular responses. We hypothesized that
      interactions between microbial compounds could modulate inflammatory cytokine
      responses in vitro. We investigated monocyte production of the pro-inflammatory
      cytokine tumour necrosis factor-alpha (TNF-alpha) and the regulatory cytokine
      interleukin-10 (IL-10) after combined exposure to the fungal cell wall
      polysaccharide mannan and to the beta-glucan laminarin, the mycotoxin citrinin
      and bacterial lipopolysaccharide (LPS). Interactions between the cell wall
      microbial compounds were estimated statistically in a general linear mixed model.
      We found that LPS (100 ng/ml) and the used beta-glucan (up to 1000 microg/ml)
      significantly interacted with each other to reduce TNF-alpha production. Mannan
      (up to 100 microg/ml) did not interact with the beta-glucan, but interacted with
      LPS. IL-10 production was induced by LPS only. The mycotoxin citrinin did not
      induce cytokine production, but was toxic to the cells in a dose- and time
      dependent manner. However, non-toxic doses of citrinin reduced LPS-induced IL-10
      production while LPS-induced TNF-alpha production was not similarly reduced by
      citrinin. In conclusion, interactions between microbial compounds can modulate
      cellular inflammatory cytokine production and experimental investigations of one
      compound at a time could give misleading conclusions about these combined
      effects.

PMID- 19594492
TI  - Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study
      including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2,
      CD117 (c-kit), and YKL-40.
AB  - Chondroid tumors comprise a heterogenous group of benign to overt malignant
      neoplasms, which may be difficult to differentiate from one another by
      histological examination. A group of 43 such tumors was stained with nine
      relevant antibodies in an attempt to find consistent marker profile(s) for the
      different subgroups. Archival material from three extraskeletal myxoid
      chondrosarcomas, five chordomas, five chondromyxoid fibromas, five
      chondroblastomas and 25 chondrosarcomas was stained with antibodies against
      osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c
      kit) and YKL-40. All 25 chondrosarcomas showed a positive staining reaction for
      D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%).
      Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with
      a positive reaction for actin, and all chondroblastomas (n=5) and extraskeletal
      myxoid chondrosarcomas (n=3) were positive for bcl-2. In contrast to all other
      tumors, two of three extraskeletal myxoid chondrosarcomas were also positive for
      CD17 and negative for osteonectin, cox-2, mdm-2 and actin. All five chordomas
      were negative for D2-40 and positive for mdm-2 and YKL-40. The diagnosis of
      chondrosarcoma may be aided by its positivity for D2-40 and YKL-40 and its lack
      of reactivity for actin and CD117. This should be seen in the light of no
      reaction for D2-40 in chordomas and a corresponding lack of reaction for
      osteonectin, cox-2, mdm-2 and actin in extraskeletal myxoid chondrosarcomas. A
      convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas
      and chondroblastomas may also be helpful in differentiating these tumors from
      chondrosarcomas.

PMID- 19594493
TI  - Molecular characterization of CTX-M-15-producing clinical isolates of Escherichia
      coli reveals the spread of multidrug-resistant ST131 (O25:H4) and ST964 (O102:H6)
      strains in Norway.
AB  - Nationwide, CTX-M-producing clinical Escherichia coli isolates from the Norwegian
      ESBL study in 2003 (n=45) were characterized on strain and plasmid levels.
      Bla(CTX-M) allele typing, characterization of the genetic environment,
      phylogenetic groups, pulsed field gel electrophoresis (PFGE), serotyping and
      multilocus sequence typing were performed. Plasmid analysis included S1-nuclease
      PFGE, polymerase chain reaction-based replicon typing, plasmid transfer and
      multidrug resistance profiling. Bla(CTX-M-15) (n=23; 51%) and bla(CTX-M-14)
      (n=11; 24%) were the major alleles of which 18 (78%) and 6 (55%), respectively,
      were linked to ISEcp1. Thirty-two isolates were of phylogenetic groups B2 and D.
      Isolates were of 29 different XbaI-PFGE-types including six regional clusters.
      Twenty-three different O:H serotypes were found, dominated by O25:H4 (n=9, 20%)
      and O102:H6 (n=9, 20%). Nineteen different STs were identified, where ST131 (n=9,
      20%) and ST964 (n=7, 16%) were dominant. Bla(CTX-M) was found on > or =100 kb
      plasmids (39/45) of 10 different replicons dominated by IncFII (n=39, 87%), FIB
      (n=20, 44%) and FIA (n=19, 42%). Thirty-nine isolates (87%) displayed co
      resistance to other classes of antibiotics. A transferable CTX-M phenotype was
      observed in 9/14 isolates. This study reveals that the majority of CTX-M-15
      expressing strains in Norway are part of the global spread of multidrug-resistant
      ST131 and ST-complex 405, associated with ISEcp1 on transferrable IncFII
      plasmids.

PMID- 19594495
TI  - Somatic mutation of the death domain of TNF-R1 is rare in common cancers.

PMID- 19594494
TI  - Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid
      production, disabling the protection against polymorphonuclear leukocytes.
AB  - Many of the virulence factors produced by the opportunistic human pathogen
      Pseudomonas aeruginosa are quorum-sensing (QS) regulated. Among these are
      rhamnolipids, which have been shown to cause lysis of several cellular components
      of the human immune system, e.g. monocyte-derived macrophages and
      polymorphonuclear leukocytes (PMNs). We have previously shown that rhamnolipids
      produced by P. aeruginosa cause necrotic death of PMNs in vitro. This raises the
      possibility that rhamnolipids may function as a 'biofilm shield'in vivo, which
      contributes significantly to the increased tolerance of P. aeruginosa biofilms to
      PMNs. In the present study, we demonstrate the importance of the production of
      rhamnolipids in the establishment and persistence of P. aeruginosa infections,
      using an in vitro biofilm system, an intraperitoneal foreign-body model and a
      pulmonary model of P. aeruginosa infections in mice. Our experimental data showed
      that a P. aeruginosa strain, unable to produce any detectable rhamnolipids due to
      an inactivating mutation in the single QS-controlled rhlA gene, did not induce
      necrosis of PMNs in vitro and exhibited increased clearance compared with its
      wild-type counterpart in vivo. Conclusively, the results support our model that
      rhamnolipids are key protective agents of P. aeruginosa against PMNs.

PMID- 19594496
TI  - Advanced glycation end products induce actin rearrangement and subsequent
      hyperpermeability of endothelial cells.

PMID- 19594497
TI  - Abstracts of the 9th Congress of the European Association for Clinical
      Pharmacology and Therapeutics. July 12-15, 2009. Edinburgh, United Kingdom.

PMID- 19594500
TI  - Seeking definition.

PMID- 19594502
TI  - Beyond genetics: childhood affective trauma in bipolar disorder.
AB  - OBJECTIVES: Despite the demonstrated high heritability of bipolar disorder, few
      susceptibility genes have been identified and linkage and/or association studies
      have produced conflicting results. This search for susceptibility genes is
      hampered by several methodological limitations, and environmental risk factors
      for the disease (requiring incorporation into analyses) remain misunderstood.
      Among them, childhood trauma is probably the most promising environmental factor
      for further investigation. The objectives are to review the arguments in favor of
      an association between childhood trauma and bipolar disorder and to discuss the
      interpretations of such an observation. METHODS: We computed a literature search
      using PubMed to identify relevant publications concerning childhood trauma and
      bipolar disorder. We also present some personal data in this field. RESULTS:
      Growing evidence suggests that incidences of childhood trauma are frequent and
      severe in bipolar disorder, probably affect the clinical expression of the
      disease in terms of suicidal behavior and age at onset, and also have an
      insidious influence on the affective functioning of patients between episodes.
      The relationships between childhood trauma and bipolar disorder suggest several
      interpretations, mainly a causal link, a neurodevelopmental consequence, or the
      intergenerational transmission of traumatic experiences. The neurobiological
      consequences of childhood trauma on a maturing brain remain unclear, although
      such stressors may alter the organization of brain development, leading to
      inadequate affective regulation. CONCLUSIONS: Childhood trauma is associated with
      bipolar disorder and its clinical expression and may interact with genetic
      susceptibility factors. Although not completely understood, the relationships
      between childhood trauma and bipolar disorder require further attention. Several
      suggestions for further exploration of this environmental factor and of its
      interaction with susceptibility genes are proposed.

PMID- 19594501
TI  - Verapamil augmentation of lithium treatment improves outcome in mania
      unresponsive to lithium alone: preliminary findings and a discussion of
      therapeutic mechanisms.
AB  - OBJECTIVES: Attenuation of protein kinase C (PKC) is a mechanism common to both
      established (lithium, valproate) and some novel (tamoxifen) antimanic agents.
      Verapamil, although primarily known as a calcium channel blocker, also has PKC
      inhibitory activity. Verapamil has shown antimanic activity in some but not all
      studies. Therefore, we investigated verapamil, used alone or as an adjunctive
      treatment, in manic patients who did not respond to an initial adequate trial of
      lithium. METHODS: Each study phase lasted three weeks. Subjects were treated
      openly with lithium in Phase 1 (n = 45). Those who failed to respond were
      randomly assigned to double-blind treatment in Phase 2 with either verapamil (n =
      10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to
      combined verapamil/lithium in Phase 3. RESULTS: Response in Phase 2 did not
      differ significantly between verapamil and continued-lithium. During Phase 3,
      response to combined treatment was significantly better than overall response to
      monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved
      during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F =
      4.34, p = 0.013), compared with 10.5% improvement during Phase 2. CONCLUSIONS: In
      this preliminary investigation, verapamil monotherapy did not demonstrate
      antimanic efficacy. By contrast, the combination of verapamil plus lithium was
      highly efficacious. Our findings thus suggest that verapamil may have potential
      utility as an adjunct to lithium. This effect may be mediated by additive actions
      on PKC inhibition, which may be an important mechanism for antimanic agents in
      general.

PMID- 19594503
TI  - Cognitive functioning in euthymic bipolar I and bipolar II patients.
AB  - OBJECTIVE: There is growing evidence of cognitive impairment as a trait factor in
      bipolar disorder. The generalizability of this finding is limited because
      previous studies have either focussed exclusively on bipolar I disorder or have
      analysed mixed patient groups. Thus, it is still largely unknown whether bipolar
      II patients perform differently from bipolar I patients on measures of cognitive
      functioning. METHODOLOGY: A total of 65 patients with bipolar I disorder, 38 with
      bipolar II disorder, and 62 healthy controls participated in the study. Patients
      had to be euthymic for at least one month. Clinical and demographic variables
      were collected in a clinical interview and with the Structured Clinical Interview
      for DSM-IV. Cognitive functioning was assessed using a neuropsychological
      battery. Univariate and multivariate analyses of variance were conducted for
      analyzing possible differences between the groups. RESULTS: The multivariate
      analysis of covariance (MANCOVA) indicated overall differences in
      neuropsychological performance between the three groups (Pillai Spur: F 1.96, p =
      0.003). Post hoc comparisons revealed that patients with bipolar I disorder
      showed significantly lower scores in psychomotor speed, working memory, verbal
      learning, delayed memory, and executive functions than healthy controls. Patients
      with bipolar II disorder showed significant deficits in psychomotor speed,
      working memory, visual/constructional abilities, and executive functions compared
      to controls, but not on verbal learning and delayed memory. The two patient
      groups did not differ significantly from each other on any domain tested.
      CONCLUSION: These results support a similar pattern of cognitive deficits in both
      subtypes of bipolar disorder.

PMID- 19594504
TI  - Neuropsychological and electrophysiological indices of neurocognitive dysfunction
      in bipolar II disorder.
AB  - OBJECTIVES: There are conflicting findings regarding the nature and degree of
      neurocognitive dysfunction in bipolar II disorder (BD II). The aim of this study
      was to describe different levels of neurocognitive functioning in BD II by
      combining behavior-based methods (neuropsychological testing) and event-related
      potentials (ERP). METHODS: Twenty-five consecutively referred outpatients
      fulfilling DSM-IV criteria for BD II and 28 matched controls performed a
      neuropsychological test battery targeting working memory/attention, executive
      functions, verbal and visual memory, and psychomotor speed. In addition, ERPs for
      measuring early and controlled stages of information processing were recorded
      using a duration mismatch negativity (MMN) paradigm and a three-tone auditory
      oddball paradigm. RESULTS: Compared to controls, BD II patients' performance was
      significantly impaired on all neuropsychological measures, except for phonemic
      verbal fluency, with moderate to strong effect sizes ranging from 0.62 to 1.34.
      The ERP results indicate dysfunctions in early stages of information processing,
      showing a significant MMN latency increase and attenuated frontal amplitudes in
      BD II patients. Female patients showed increased P3a latency compared to female
      controls, but no group differences were found for P3b latency or amplitude, the
      ERP component expressing controlled information processing. CONCLUSIONS: The
      functional significance of neuropsychological impairment is discussed.
      Differences regarding some aspects of executive function may be related to
      psychomotor speed, and not primarily to dysexecutive functioning. ERP results
      must be interpreted with caution, but the differences found in MMN latency and
      amplitudes may be related to fronto-temporal circuitry underlying pre-attentive
      stimulus change detection as measured by MMN, and are discussed in relation to
      previous research on MMN in other neuropsychiatric conditions.

PMID- 19594505
TI  - The factor structure of clinical symptoms in mixed and manic episodes prior to
      and after antipsychotic treatment.
AB  - BACKGROUND: While the factor structure of clinical symptoms in schizophrenia has
      been examined and provided crucial information about the illness, there is much
      less information available in bipolar disorder. This study examined the structure
      of symptoms of bipolar disorder at an unmedicated baseline assessment and after
      double-blind treatment with ziprasidone, haloperidol, or placebo. We
      hypothesized, consistent with recent studies of schizophrenia, that the factor
      structure after treatment would be similar to the structure of untreated symptoms
      at study baseline. METHODS: Hospitalized patients with manic (n = 363) or mixed
      (n = 71) bipolar episodes were rated with the Hamilton Depression Rating Scale
      (HAM-D) and the Mania Rating Scale [(MRS); derived from the Schedule for
      Affective Disorders and Schizophrenia - Change Bipolar Scale]. After 21 days of
      double-blind treatment, all patients were again rated with the MRS and HAM-D.
      RESULTS: Exploratory orthogonal factor analysis (varimax rotation) including both
      HAM-D total scores and the MRS items found different five-factor solutions for
      mixed and manic patients at the unmedicated baseline assessment. Confirmatory
      modeling indicated that these models, with some modifications, fit the data well.
      At the endpoint, however, a single-factor solution was found for mixed and manic
      groups. IMPLICATIONS: Symptomatology in bipolar disorder is multifactorial in an
      acute and unmedicated state, with slightly different factor structures for mixed
      and manic episodes. Following treatment, a single severity dimension is detected.
      These results suggest that symptom dimensions in mania may be different from
      those seen in schizophrenia, where different elements of symptoms have been
      proven to have different functional correlates and treatment response.

PMID- 19594506
TI  - Treatment-emergent mania/hypomania during antidepressant monotherapy in patients
      with rapid cycling bipolar disorder.
AB  - OBJECTIVE: To study treatment-emergent mania/hypomania (TEM) associated with
      second-generation antidepressant monotherapy in patients with rapid cycling
      bipolar disorder (RCBD). METHODS: Data of patients with RCBD (n = 180) enrolled
      into two clinical trials were used to study the risk for TEM during second
      generation antidepressant monotherapy. History of TEM was retrospectively
      determined at the initial assessment by asking patients whether they were exposed
      to second-generation antidepressants and if a hypomania/mania episode emerged
      during the first four weeks of treatment. Data were analyzed using t-test, chi
      square, and logistic regression. RESULTS: Of the 180 patients (bipolar I
      disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at
      least one antidepressant treatment. Among these patients, 94.1% (144/153) had at
      least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at
      least one TEM and 29.1% (116/399) of treatment trials were associated with TEM.
      In regression analysis, an inverse association between the number of mood
      episodes in the last 12 months and TEM was observed with an odds ratio of 0.9.
      However, gender, bipolar subtype, a lifetime history of comorbid anxiety
      disorder, substance use disorder, or psychosis, and age of mood disorder onset
      were not associated with TEM. For individual antidepressants, the rates of TEM
      varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a
      group, there was no difference between selective serotonin reuptake inhibitors
      and venlafaxine or bupropion in the incidence of TEM. CONCLUSIONS: Use of second
      generation antidepressants as monotherapy in RCBD is accompanied by clinically
      relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities
      to antidepressant TEM may exist.

PMID- 19594507
TI  - Elevated striatal and decreased dorsolateral prefrontal cortical activity in
      response to emotional stimuli in euthymic bipolar disorder: no associations with
      psychotropic medication load.
AB  - OBJECTIVE: To examine abnormal patterns of frontal cortical-subcortical activity
      in response to emotional stimuli in euthymic individuals with bipolar disorder
      type I in order to identify trait-like, pathophysiologic mechanisms of the
      disorder. We examined potential confounding effects of total psychotropic
      medication load and illness variables upon neural abnormalities. METHOD: We
      analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to
      mild and intense happy, fearful and neutral faces. RESULTS: Relative to healthy
      individuals, bipolar subjects had significantly increased left striatal activity
      in response to mild happy faces (p < 0.05, corrected), decreased right
      dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild
      and intense happy faces, and decreased left DLPFC activity in response to
      neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and
      healthy individuals did not differ in amygdala activity in response to either
      emotion. In bipolar individuals, there was no significant association between
      medication load and abnormal activity in these regions, but a negative
      relationship between age of illness onset and amygdala activity in response to
      mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar
      individuals with comorbidities showed a trend increase in left striatal activity
      in response to mild happy faces. CONCLUSIONS: Abnormally increased striatal
      activity in response to potentially rewarding stimuli and decreased DLPFC
      activity in response to other emotionally salient stimuli may underlie mood
      instabilities in euthymic bipolar individuals, and are more apparent in those
      with comorbid diagnoses. No relationship between medication load and abnormal
      neural activity in bipolar individuals suggests that our findings may reflect
      pathophysiologic mechanisms of the illness rather than medication confounds.
      Future studies should examine whether this pattern of abnormal neural activity
      could distinguish bipolar from unipolar depression.

PMID- 19594508
TI  - An fMRI investigation of working memory and sadness in females with bipolar
      disorder: a brief report.
AB  - OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have documented
      abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior
      cingulate cortex in bipolar disorder in the context of working memory tasks. It
      is increasingly recognized that DLPFC regions play a role in mood regulation and
      the integration of emotion and cognition. The purpose of the present study was to
      investigate with fMRI the interaction between acute sadness and working memory
      functioning in individuals with bipolar disorder. METHODS: Nine depressed
      individuals with DSM-IV bipolar I disorder (BP-I) and 17 healthy control
      participants matched for age, gender, education, and IQ completed a 2-back
      working memory paradigm under no mood induction, neutral state, or acute sadness
      conditions while undergoing fMRI scanning. Functional MRI data were analyzed with
      SPM2 using a random-effects model. RESULTS: Behaviorally, BP-I subjects performed
      equally well as control participants on the 2-back working memory paradigm.
      Compared to control participants, individuals with BP-I were characterized by
      more sadness-specific activation increases in the left DLPFC (BA 9/46) and left
      dorsal anterior cingulate (dACC). CONCLUSIONS: Our study documents sadness
      specific abnormalities in the left DLPFC and dACC in bipolar disorder that
      suggest difficulties in the integration of emotion (sadness) and cognition. These
      preliminary findings require further corroboration with larger sample sizes of
      medication-free subjects.

PMID- 19594509
TI  - A functional MRI study of Theory of Mind in euthymic bipolar disorder patients.
AB  - OBJECTIVES: To determine the neural responses invoked in Theory of Mind (ToM) in
      euthymic bipolar patients as compared with healthy subjects. METHODS: This study
      examined 20 euthymic bipolar patients (11 males and 9 females) and 20 suitably
      matched healthy subjects using functional magnetic resonance imaging (fMRI) while
      subjects were engaged in a ToM task. Within-scanner eye movements were monitored
      to ensure task engagement. The activation paradigm involved observing ToM and
      random-motion animated sequences in a block design. Both within group (ToM versus
      random motion) and random effects between group analyses were performed on fMRI
      data using the BrainVoyager software package. Demographic and clinical data,
      along with subject ratings of fMRI stimuli, were collated and analysed. RESULTS:
      Patients were compromised in their ability to appropriately rate the ToM stimuli
      and assess them for intention as compared to healthy subjects. This was reflected
      in the fact that patients had few within-group significant activations in
      response to ToM animated sequences, namely, the left anterior cingulate, and
      precuneus and cuneus bilaterally. In contrast, robust activations in response to
      ToM animated sequences in healthy subjects were widespread and involved regions
      recognized for mental state reasoning, in particular the insula, inferior
      frontal, supramarginal and angular gyri, and temporal cortex. The between-group
      random effects analysis exclusively favoured the healthy subjects, with many
      activations occurring in regions overlapping with those found in the within-group
      analyses. CONCLUSIONS: The findings of this novel neuroimaging study suggest that
      in a social context, euthymic bipolar patients, though seemingly well and capable
      of engaging aspects of ToM, are perhaps constrained in their ability to mentalize
      fully, and furthermore cannot reliably adopt an alternate cognitive perspective
      when appropriate. Impairment of this capacity, though subtle, may in effect
      compromise their ability to understand the emotions and intentions of others, and
      also may limit appreciation of their own illness and symptoms. Such a deficit in
      bipolar disorder perhaps impacts upon interpersonal relationships and adversely
      affects social cognition and clinical functioning. The potential implications of
      this putative mentalizing compromise in euthymic patients with bipolar disorder
      are substantial, both for the individual and for understanding the neural
      substrate of the illness, and therefore warrant further investigation.

PMID- 19594510
TI  - Why antidepressants are not antidepressants: STEP-BD, STAR*D, and the return of
      neurotic depression.
AB  - The widely held clinical view of 'antidepressants' as highly effective and
      specific for the treatment of all types of depressive disorders is exaggerated.
      This sobering conclusion is supported by recent findings from the NIMH-sponsored
      STEP-BD and STAR*D projects. Antidepressants have limited short-term efficacy in
      unipolar depressive disorders and less in acute bipolar depression; their long
      term prophylactic effectiveness in recurrent unipolar major depression remains
      uncertain, and is doubtful in recurrent bipolar depression. These limitations
      may, in part, reflect the excessively broad concept of major depression as well
      as unrealistic expectations of universal efficacy of drugs considered
      'antidepressants.' Treatment-refractory depression may reflect failure to
      distinguish depressive conditions, particularly bipolar disorder, that are
      inherently less responsive to antidepressants. Antidepressants probably should be
      avoided in bipolar depression, mixed manic-depressive states, and in neurotic
      depression. Expectations of antidepressants for specific types of patients with
      symptoms of depression or anxiety require critical re-evaluation. A revival of
      the concept of neurotic depression would make it possible to identify patients
      with mild-to-moderate, chronic or episodic dysthymia and anxiety who are unlikely
      to benefit greatly from antidepressants. Diagnostic criteria for a revival of the
      concept of neurotic depression are proposed.

PMID- 19594511
TI  - The modern pharmacopoeia: a return to depressive realism?

PMID- 19594512
TI  - Antidepressant treatment practice in the face of STAR*D and STEP-BD.

PMID- 19594513
TI  - Upping the ante on antidepressants.

PMID- 19594516
TI  - Haemostatic agents during laparoscopic nephron-sparing surgery: what about
      TachoSil?

PMID- 19594515
TI  - The role of magnetic resonance imaging in targeting prostate cancer in patients
      with previous negative biopsies and elevated prostate-specific antigen levels.

PMID- 19594519
TI  - Anatomical reconstruction of the rhabdosphincter after radical prostatectomy.

PMID- 19594518
TI  - Is the current antibiotic prophylaxis policy in transrectal prostate biopsy still
      safe?

PMID- 19594524
TI  - Medication errors: EMERGing solutions.

PMID- 19594526
TI  - Medication errors: definitions and classification.
AB  - 1. To understand medication errors and to identify preventive strategies, we need
      to classify them and define the terms that describe them. 2. The four main
      approaches to defining technical terms consider etymology, usage, previous
      definitions, and the Ramsey-Lewis method (based on an understanding of theory and
      practice). 3. A medication error is 'a failure in the treatment process that
      leads to, or has the potential to lead to, harm to the patient'. 4. Prescribing
      faults, a subset of medication errors, should be distinguished from prescription
      errors. A prescribing fault is 'a failure in the prescribing [decision-making]
      process that leads to, or has the potential to lead to, harm to the patient'. The
      converse of this, 'balanced prescribing' is 'the use of a medicine that is
      appropriate to the patient's condition and, within the limits created by the
      uncertainty that attends therapeutic decisions, in a dosage regimen that
      optimizes the balance of benefit to harm'. This excludes all forms of prescribing
      faults, such as irrational, inappropriate, and ineffective prescribing,
      underprescribing and overprescribing. 5. A prescription error is 'a failure in
      the prescription writing process that results in a wrong instruction about one or
      more of the normal features of a prescription'. The 'normal features' include the
      identity of the recipient, the identity of the drug, the formulation, dose,
      route, timing, frequency, and duration of administration. 6. Medication errors
      can be classified, invoking psychological theory, as knowledge-based mistakes,
      rule-based mistakes, action-based slips, and memory-based lapses. This
      classification informs preventive strategies.

PMID- 19594525
TI  - Medication errors: problems and recommendations from a consensus meeting.
AB  - Here we discuss 15 recommendations for reducing the risks of medication errors:
      1. Provision of sufficient undergraduate learning opportunities to make medical
      students safe prescribers. 2. Provision of opportunities for students to practise
      skills that help to reduce errors. 3. Education of students about common types of
      medication errors and how to avoid them. 4. Education of prescribers in taking
      accurate drug histories. 5. Assessment in medical schools of prescribing
      knowledge and skills and demonstration that newly qualified doctors are safe
      prescribers. 6. European harmonization of prescribing and safety recommendations
      and regulatory measures, with regular feedback about rational drug use. 7.
      Comprehensive assessment of elderly patients for declining function. 8.
      Exploration of low-dose regimens for elderly patients and preparation of special
      formulations as required. 9. Training for all health-care professionals in drug
      use, adverse effects, and medication errors in elderly people. 10. More
      involvement of pharmacists in clinical practice. 11. Introduction of integrated
      prescription forms and national implementation in individual countries. 12.
      Development of better monitoring systems for detecting medication errors, based
      on classification and analysis of spontaneous reports of previous reactions, and
      for investigating the possible role of medication errors when patients die. 13.
      Use of IT systems, when available, to provide methods of avoiding medication
      errors; standardization, proper evaluation, and certification of clinical
      information systems. 14. Nonjudgmental communication with patients about their
      concerns and elicitation of symptoms that they perceive to be adverse drug
      reactions. 15. Avoidance of defensive reactions if patients mention symptoms
      resulting from medication errors.

PMID- 19594527
TI  - The pathophysiology of medication errors: how and where they arise.
AB  - 1. Errors arise when an action is intended but not performed; errors that arise
      from poor planning or inadequate knowledge are characterized as mistakes; those
      that arise from imperfect execution of well-formulated plans are called slips
      when an erroneous act is committed and lapses when a correct act is omitted. 2.
      Some tasks are intrinsically prone to error. Examples are tasks that are
      unfamiliar to the operator or performed under pressure. Tasks that require the
      calculation of a dosage or dilution are especially susceptible to error. 3. The
      tasks of prescribing, preparation, and administration of medicines are complex,
      and are carried out within a complex system; errors can occur at each of many
      steps and the error rate for the overall process is therefore high. 4. The error
      rate increases when health-care professionals are inexperienced, inattentive,
      rushed, distracted, fatigued, or depressed; orthopaedic surgeons and nurses may
      be more likely than other health-care professionals to make medication errors. 5.
      Medication error rates in hospital are higher in paediatric departments and
      intensive care units than elsewhere. 6. Rates of medication errors may be higher
      in very young or very old patients. 7. Intravenous antibiotics are the drugs most
      commonly involved in medication errors in hospital; antiplatelet agents,
      diuretics, and non-steroidal anti-inflammatory drugs are most likely to account
      for 'preventable admissions'. 8. Computers effectively reduce the rates of easily
      counted errors. It is not clear whether they can save lives lost through rare but
      dangerous errors in the medication process.

PMID- 19594529
TI  - The epidemiology of medication errors: how many, how serious?
AB  - 1. Errors will always occur in any system, but it is essential to identify causes
      and attempt to minimize risks. 2. Although it is difficult to quantify precisely
      the extent of medication errors, they are clearly frequent and often avoidable,
      representing a major threat to patient safety. 3. Many of the consequences of
      these errors can be prevented by the intervention of pharmacists. 4. Some errors
      are due to the conditions under which prescribers work; where possible these
      should be improved (for example, low staffing levels). 5. Computerized
      prescribing can help but can also generate its own inherent errors. 6. Improved
      training of prescribers at the undergraduate and postgraduate levels is vital, a
      fact that is now being belatedly recognized.

PMID- 19594530
TI  - Medication errors: prescribing faults and prescription errors.
AB  - 1. Medication errors are common in general practice and in hospitals. Both errors
      in the act of writing (prescription errors) and prescribing faults due to
      erroneous medical decisions can result in harm to patients. 2. Any step in the
      prescribing process can generate errors. Slips, lapses, or mistakes are sources
      of errors, as in unintended omissions in the transcription of drugs. Faults in
      dose selection, omitted transcription, and poor handwriting are common. 3.
      Inadequate knowledge or competence and incomplete information about clinical
      characteristics and previous treatment of individual patients can result in
      prescribing faults, including the use of potentially inappropriate medications.
      4. An unsafe working environment, complex or undefined procedures, and inadequate
      communication among health-care personnel, particularly between doctors and
      nurses, have been identified as important underlying factors that contribute to
      prescription errors and prescribing faults. 5. Active interventions aimed at
      reducing prescription errors and prescribing faults are strongly recommended.
      These should be focused on the education and training of prescribers and the use
      of on-line aids. The complexity of the prescribing procedure should be reduced by
      introducing automated systems or uniform prescribing charts, in order to avoid
      transcription and omission errors. Feedback control systems and immediate review
      of prescriptions, which can be performed with the assistance of a hospital
      pharmacist, are also helpful. Audits should be performed periodically.

PMID- 19594528
TI  - The epidemiology of medication errors: the methodological difficulties.
AB  - 1. Medication errors should be amenable to epidemiological analysis, giving
      insights into the causes of error and the effects of interventions to prevent
      them or reduce harm from them. 2. There are formidable difficulties in
      establishing the rates of medication errors. 3. There is no agreement on a clear
      operational definition of the condition. 4. The methods used to enumerate cases
      so far have been unreliable or incomplete or both. 5. There is disagreement about
      whether cases of error that do not cause harm should be included in calculations
      of error rates. 6. When harm occurs in association with drug therapy, it is often
      unclear whether the harm might have been prevented, and its occurrence should
      therefore be considered to result from error. 7. The denominator for calculating
      the rate of error is both ill-defined and inconsistently measured. Better
      definitions, more complete evaluation, and more thorough impact assessment may
      improve matters.

PMID- 19594531
TI  - Medication errors in elderly people: contributing factors and future
      perspectives.
AB  - 1. Older people have substantial interindividual variability in health,
      disability, age-related changes, polymorbidity, and associated polypharmacy,
      making generalization of prescribing recommendations difficult. 2. Medication use
      in older adults is often inappropriate and erroneous, partly because of the
      complexities of prescribing and partly because of many patient, provider, and
      health system factors that substantially influence the therapeutic value of
      medications in aged people. 3. A high prevalence of medication errors in older
      adults results on the one hand from accumulation of factors that contribute to
      medication errors in all age groups, such as polypharmacy, polymorbidity,
      enrollment in several disease-management programmes, and fragmentation of care.
      On the other hand, specific geriatric aspects play a role in these medication
      errors; these include age-related pharmacological changes, lack of specific
      evidence on the efficacy and safety of medications, underuse of comprehensive
      geriatric assessment, less availability of drug formulations offering geriatric
      doses, and inadequate harmonization of geriatric recommendations across Europe.
      4. The dearth of geriatric clinical pharmacology and clinical pharmacy services
      compounds the difficulties. 5. There are gaps in research and clinical practice
      that lead to frequent medication errors in older adults, which must be solved by
      future studies and by regulatory measures in order to support errorless and
      appropriate use medications in these people.

PMID- 19594532
TI  - Medication errors: the role of the patient.
AB  - 1. Patients and their carers will usually be the first to notice any observable
      problems resulting from medication errors. They will probably be unable to
      distinguish between medication errors, adverse drug reactions, or 'side effects'.
      2. Little is known about how patients understand drug related problems or how
      they make attributions of adverse effects. Some research suggests that patients'
      cognitive models of adverse drug reactions bear a close relationship to models of
      illness perception. 3. Attributions of adverse drug reactions are related to
      people's previous experiences and to their level of education. The evidence
      suggests that on the whole patients' reports of adverse drug reactions are
      accurate. However, patients do not report all the problems they perceive and are
      more likely to report those that they do perceive as severe. Patients may not
      report problems attributed to their medications if they are fearful of doctors'
      reactions. Doctors may respond inappropriately to patients' concerns, for example
      by ignoring them. Some authors have proposed the use of a symptom checklist to
      elicit patients' reports of suspected adverse drug reactions. 4. Many patients
      want information about adverse drug effects, and the challenge for the
      professional is to judge how much information to provide and the best way of
      doing so. Professionals' inappropriate emphasis on adherence may be dangerous
      when a medication error has occurred. 5. Recent NICE guidelines recommend that
      professionals should ask patients if they have any concerns about their
      medicines, and this approach is likely to yield information conducive to the
      identification of medication errors.

PMID- 19594533
TI  - Prevention of medication errors: detection and audit.
AB  - 1. Medication errors have important implications for patient safety, and their
      identification is a main target in improving clinical practice errors, in order
      to prevent adverse events. 2. Error detection is the first crucial step.
      Approaches to this are likely to be different in research and routine care, and
      the most suitable must be chosen according to the setting. 3. The major methods
      for detecting medication errors and associated adverse drug-related events are
      chart review, computerized monitoring, administrative databases, and claims data,
      using direct observation, incident reporting, and patient monitoring. All of
      these methods have both advantages and limitations. 4. Reporting discloses
      medication errors, can trigger warnings, and encourages the diffusion of a
      culture of safe practice. Combining and comparing data from various and
      encourages the diffusion of a culture of safe practice sources increases the
      reliability of the system. 5. Error prevention can be planned by means of
      retroactive and proactive tools, such as audit and Failure Mode, Effect, and
      Criticality Analysis (FMECA). Audit is also an educational activity, which
      promotes high-quality care; it should be carried out regularly. In an audit cycle
      we can compare what is actually done against reference standards and put in place
      corrective actions to improve the performances of individuals and systems. 6.
      Patient safety must be the first aim in every setting, in order to build safer
      systems, learning from errors and reducing the human and fiscal costs.

PMID- 19594534
TI  - Prevention of medication errors: teaching and training.
AB  - 1. Poor prescribing is probably the most common cause of preventable medication
      errors in hospitals, and many of these events involve junior doctors who have
      recently graduated. Prescribing is a complex skill that depends on a sound
      knowledge of medicines, an understanding of the principles of clinical
      pharmacology, the ability to make judgements concerning risks and benefits, and
      ideally experience. It is not surprising that errors occur. 2. The challenge of
      being a prescriber is probably greater now than ever before. Medical education
      has changed radically in the last 20 years, reflecting concerns about an
      overburdened curriculum and lack of focus on social sciences. In the UK, these
      changes have resulted in less teaching in clinical pharmacology and practical
      prescribing as guaranteed features of undergraduate training and assessment.
      There has been growing concern, not least from students, that medical school
      training is not sufficient to prepare them for the pressures of becoming
      prescribers. Similar concerns are being expressed in other countries. While
      irrefutable evidence that these changes are related to medication errors
      identified in practice, there is circumstantial evidence that this is so. 3.
      Systems analysis of errors suggests that knowledge and training are relevant
      factors in causation and that focused education improves prescribing performance.
      We believe that there is already sufficient evidence to support a careful review
      of how students are trained to become prescribers and how these skills are
      fostered in the postgraduate years. We provide a list of guiding principles on
      which training might be based.

PMID- 19594536
TI  - Medication errors: the importance of an accurate drug history.
AB  - 1. Medication histories are important in preventing prescription errors and
      consequent risks to patients. Apart from preventing prescription errors, accurate
      medication histories are also useful in detecting drug-related pathology or
      changes in clinical signs that may be the result of drug therapy. A good
      medication history should encompass all currently and recently prescribed drugs,
      previous adverse drug reactions including hypersensitivity reactions, any over
      the counter medications, including herbal or alternative medicines, and adherence
      to therapy. 2. Medication history errors, such as omitting drugs erroneously, are
      common and often have the potential to harm the patient. Hypersensitivity
      reactions are often poorly documented or not explored in detail, which may lead
      to unnecessary avoidance of a drug. Accurate documentation of concomitant herbal
      or alternative therapies is rare, despite the importance they may have in causing
      adverse effects or drug-drug interactions. Polypharmacy, specific drugs, and
      clinical specialty can affect the risk of medication history errors. 3. There are
      various strategies to reduce medication history errors. Pharmacists are better at
      taking an accurate medication history than many physicians or nurses. In the
      context of acute hospital admissions they reduce error, the risks of adverse drug
      reactions, and prescription costs. Electronic prescribing may reduce
      transcription errors, but it can facilitate other errors and still depends on an
      accurate medication history. 4. Education of prescribers, both in clinical
      pharmacology and in taking accurate medication histories is vitally important in
      reducing errors.

PMID- 19594535
TI  - Do educational interventions improve prescribing by medical students and junior
      doctors? A systematic review.
AB  - Our aim was to review systematically the literature on educational interventions
      to improve prescribing by medical students and junior doctors. MEDLINE, EMBASE,
      Educational Resource Information Center, British Education Index, PsycINFO,
      CINAHL, TIMELIT, Cochrane Trials Database and grey literature were searched.
      Inclusion criteria were: educational interventions to improve medical student
      and/or junior doctors' prescribing, in primary or secondary care settings, and
      published after 1990. After screening 3189 records, we retrieved 11 controlled
      and four 'before-and-after' trials. Ten controlled trials showed improvements in
      the scores of the intervention group on written scenarios or clinical examination
      stations, but one study in junior doctors showed no effect on real-life
      prescription errors. Only one intervention [the World Health Organization (WHO)
      Good Prescribing Guide, in six randomized trials] had been tested in a variety of
      international settings and across a range of students at different levels. All
      four 'before-and-after' trials reported significant improvements in written tests
      or clinical stations. However, most studies tested only small numbers of
      participants and were affected by a range of methodological flaws. There is only
      moderate evidence in the literature to inform medical schools about how to
      prepare medical students for the challenges of prescribing. The WHO Good
      Prescribing Guide is the only model that has been widely used and shown to
      improve prescribing. Although it is based on sound principles, there is a need
      for further development. Robust methods of assessment are required to show
      clearly whether particular teaching interventions are successful.

PMID- 19594537
TI  - Medication errors: the importance of safe dispensing.
AB  - 1. Although rates of dispensing errors are generally low, further improvements in
      pharmacy distribution systems are still important because pharmacies dispense
      such high volumes of medications that even a low error rate can translate into a
      large number of errors. 2. From the perspective of pharmacy organization and
      quality assurance, pharmacists should intensify their checking of prescriptions,
      in order to reduce prescription errors, and should implement strategies to
      communicate adequately with patients, in order to prevent administration errors.
      More and better studies are still needed in these areas. 3. More research is also
      required into: dispensing errors in out-patient health-care settings, such as
      community pharmacies in the USA and Europe; dispensing errors in hospitals and
      out-patient health-care settings in middle- and low-income countries; and the
      underlying causes of dispensing errors.

PMID- 19594539
TI  - Medication errors: pharmacovigilance centres in detection and prevention.
AB  - 1. Detecting medication errors needs collaboration between various organizations,
      such as patient safety institutions, pharmacovigilance centres, and poison
      control centres. In order to evaluate the input of pharmacovigilance centres and
      poison control centres in detecting and evaluating medication errors a pilot
      project was initiated by the World Alliance for Patient Safety in collaboration
      with the Uppsala Monitoring Centre; the Moroccan pharmacovigilance centre acted
      as project coordinator. As part of this project, a questionnaire on detecting
      medication errors was circulated to pharmacovigilance centres and poison control
      centres around the world, in order to assess their ability to detect and analyse
      medication errors. 2. The results showed that through their databases
      pharmacovigilance centres can detect, identify, analyse, and classify medication
      errors and carry out root cause analysis, which is an important tool in
      preventing medication errors. 3. The duties of pharmacovigilance centres in
      preventing medication errors include informing health-care professionals about
      the importance of reporting such errors and creating a culture of patient safety.
      Pharmacovigilance centres aim to prevent medication errors in collaboration with
      poison control centres. Such collaboration allows improved detection and improved
      preventive strategies. In addition, collaboration with regulatory authorities is
      important in finalizing decisions. 4. Collaboration between pharmacovigilance
      centres and poison control centres should be strengthened and bridges need to be
      built linking pharmacovigilance centres, poison control centres, and
      organizations dedicated to patient safety, in order to avoid duplication of
      workload.

PMID- 19594538
TI  - Medication errors: prevention using information technology systems.
AB  - 1. Given the high frequency of medication errors with resultant patient harm and
      cost, their prevention is a worldwide priority for health systems. 2. Systems
      that use information technology (IT), such as computerized physician order entry,
      automated dispensing, barcode medication administration, electronic medication
      reconciliation, and personal health records, are vital components of strategies
      to prevent medication errors, and a growing body of evidence calls for their
      widespread implementation. 3. However, important barriers, such as the high costs
      of such systems, must be addressed through economic incentives and government
      policies. 4. This paper provides a review of the current state of IT systems in
      preventing medication errors.

PMID- 19594542
TI  - Alice, Eloi, Magali and Robert: the lives of four patients with psoriasis and the
      therapeutic approaches of eight European experts.

PMID- 19594543
TI  - Effect of vascular endothelial growth factor polymorphisms on survival in
      advanced-stage non-small-cell lung cancer.
AB  - Polymorphisms have been identified in the vascular endothelial growth factor
      (VEGF) gene that may affect VEGF production. We hypothesized that such
      polymorphisms may correlate with survival outcomes among advanced-stage non-small
      cell lung cancer (NSCLC) patients. We evaluated the association between VEGF
      polymorphisms and overall survival among patients with advanced NSCLC who were
      treated with at least one cytotoxic regimen at Kyoto University Hospital between
      2003 and 2008. We investigated the following VEGF polymorphisms: -460T > C
      (rs833061), +405G > C (rs2010963), +936C > T (rs3025039), -1154G > A (rs1570360),
      and -2578C > A (rs699947). Analyses of genotype associations with survival
      outcomes were performed using Cox proportional models, Kaplan-Meier methods, and
      the log-rank test. There were 126 patients and 80 deaths. On a Cox regression
      analysis of a current and former smoker (hazards ratio [HR], 1.422; 95%
      confidence interval [CI], 1.111-1.859; P = 0.0046), poor performance status (PS)
      (HR, 2.524; 95% CI, 1.483-3.827; P = 0.0019), the VEGF -460CC genotype (HR,
      1.719; 95% CI, 1.166-2.390; P = 0.0084), VEGF -1154AA and AG genotypes (HR,
      1.482; 95% CI, 1.144-1.897; P = 0.0034), and VEGF -2578AA genotype (HR, 1.797;
      95% CI, 1.219-2.495; P = 0.0047) had a significant prognostic effect on survival
      based on univariate analysis. Based on multivariate analysis of a current and
      former smoker (HR, 1.407; 95% CI, 1.095-1.840; P = 0.0070), poor PS (HR, 2.249;
      95% CI, 1.309-3.468; P = 0.0058), and the VEGF -1154AA and AG genotypes (HR,
      1.419; 95% CI, 1.033-1.901; P = 0.0316) were significant independent prognostic
      factors for survival. In this study, polymorphisms in VEGF may affect survival in
      advanced NSCLC.

PMID- 19594544
TI  - Identification of PAK4 as a putative target gene for amplification within
      19q13.12-q13.2 in oral squamous-cell carcinoma.
AB  - Amplification of chromosomal DNA is thought to be one of the mechanisms
      activating cancer-related genes in tumors. To identify the most likely target for
      amplification in the region 19q13.12-q13.2, detected previously in SKN-3 cells by
      a genome-wide screening of DNA copy-number aberrations in a panel of oral
      squamous-cell carcinoma (OSCC) cell lines, we determined the extent of the
      amplicon, analyzed a panel of cell lines for the expression of candidate genes
      within the amplicon, and then evaluated growth-suppressive effects by knocking
      down genes of interest. Reported information about the function and/or expression
      of each gene, remarkable overexpression in SKN-3 cells and relatively frequent
      overexpression in additional OSCC lines compared with an immortalized normal oral
      epithelial cell line, and expression level-dependent proliferation-promoting
      activity led us to conclude that the p21-activated kinase 4 (PAK4) gene was the
      most likely target. An immunohistochemical analysis of primary tumors from 105
      cases of head and neck SCC including 50 cases of OSCC demonstrated the
      overexpression of PAK4 to be significantly associated with a poorer prognosis.
      These findings reveal that the PAK4 overexpression through amplification or other
      mechanisms promotes the proliferation and/or survival of OSCC cells, and that
      PAK4 might be a good diagnostic and/or therapeutic target.

PMID- 19594546
TI  - c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of
      transforming growth factor-beta signaling in diffuse-type gastric carcinoma.
AB  - c-Ski, originally identified as a proto-oncogene product, is an important
      negative regulator of transforming growth factor (TGF)-beta family signaling
      through interaction with Smad2, Smad3, and Smad4. High expression of c-Ski has
      been found in some cancers, including gastric cancer. We previously showed that
      disruption of TGF-beta signaling by dominant-negative TGF-beta type II receptor
      in a diffuse-type gastric carcinoma model accelerated tumor growth through
      induction of tumor angiogenesis by decreased expression of the anti-angiogenic
      factor thrombospondin (TSP)-1. Here, we examined the function of c-Ski in human
      diffuse-type gastric carcinoma OCUM-2MLN cells. Overexpression of c-Ski inhibited
      TGF-beta signaling in OCUM-2MLN cells. Interestingly, c-Ski overexpression
      resulted in extensive acceleration of the growth of subcutaneous xenografts in
      BALB/c nu/nu female mice (6 weeks of age). Similar to tumors expressing dominant
      negative TGF-beta type II receptor, histochemical studies revealed less fibrosis
      and increased angiogenesis in xenografted tumors expressing c-Ski compared to
      control tumors. Induction of TSP-1 mRNA by TGF-beta was attenuated by c-Ski in
      vitro, and expression of TSP-1 mRNA was decreased in tumors expressing c-Ski in
      vivo. These findings suggest that c-Ski overexpression promotes the growth of
      diffuse-type gastric carcinoma through induction of angiogenesis.

PMID- 19594545
TI  - Role of oxidation-triggered activation of JNK and p38 MAPK in black tea
      polyphenols induced apoptotic death of A375 cells.
AB  - Theaflavins (TF) and thearubigins (TR) are the major polyphenols of black tea.
      Our previous study revealed that TF- and TR-induced apoptosis of human malignant
      melanoma cells (A375) is executed via a mitochondria-mediated pathway. In our
      present study we observed the role of the three most important MAPK (ERK, JNK,
      and p38) in TF- and TR-induced apoptosis. TF and TR treatment of A375 cells led
      to sustained activation of JNK and p38 MAPK but not ERK, suggesting that JNK and
      p38 are the effector molecules in this polyphenol-induced cell death. This idea
      was further supported by subsequent studies in which JNK and p38 activation was
      inhibited by specific inhibitors. Significant inhibition was found in TF- and TR
      treated A375 cell death pretreated with JNK- or p38-specific inhibitors only.
      Further, we have found that TF and TR treatment induces a time-dependent increase
      in intracellular reactive oxygen species generation in A375 cells. Interestingly,
      treatment with the antioxidant N-acetyl cystein inhibits TF- and TR-induced JNK
      and p38 activation as well as induction of cell death in A375 cells. We also
      provide evidence demonstrating the critical role of apoptosis signal-regulating
      kinase 1 in TF- and TR-induced apoptosis in A375 cells. Taken together our
      results strongly suggest that TF and TR induce apoptotic death of A375 cells
      through apoptosis signal-regulating kinase 1, MAPK kinase, and the JNK-p38
      cascade, which is triggered by N-acetyl cystein intracellular oxidative stress.

PMID- 19594547
TI  - Phase II study of oral fludarabine in combination with rituximab for relapsed
      indolent B-cell non-Hodgkin lymphoma.
AB  - Oral fludarabine is more convenient than intravenous fludarabine in an outpatient
      setting. To assess the efficacy and toxicity of oral fludarabine in combination
      with rituximab in patients with relapsed indolent B-cell non-Hodgkin lymphoma (B
      NHL), we conducted a multicenter phase II study. Patients with relapsed indolent
      B-NHL with two or fewer prior regimens and up to 16 doses of rituximab were
      eligible. Patients received 375 mg/m(2) rituximab on day 1, and 40 mg/m(2) oral
      fludarabine once daily on days 1 through 5 every 28 days for up to six cycles.
      The primary endpoint was the overall response rate. Forty-one patients were
      enrolled, including 38 (93%) with follicular lymphoma. Thirty-four patients (83%)
      had received rituximab as prior therapy. Twenty-seven patients (66%) completed
      the planned six cycles. Dose reduction of oral fludarabine was required in 17
      patients (41%). The overall response rate was 76% (31 of 41 patients; 95%
      confidence interval, 60-88%) with a complete response rate of 68% (28 of 41
      patients; 95% confidence interval, 52-82%). Median progression-free survival for
      the 41 patients was 19.7 months (95% confidence interval, 12.3-26.5 months).
      Hematological toxicities, including grade 4 neutropenia (68%), were the most
      frequent toxicities. Non-hematological toxicities were mild, except for one
      patient who died of Pneumocystis jiroveci pneumonia 4 months after the protocol
      treatment. In conclusion, oral fludarabine in combination with rituximab is a
      highly effective and convenient therapy for patients with relapsed indolent B-NHL
      who have mostly been pretreated with rituximab.

PMID- 19594549
TI  - Utility of diagnostic tests in the follow-up of egg-allergic children.
AB  - BACKGROUND: Better knowledge of the accuracy of a skin prick test (SPT) and
      specific IgE (sIgE) levels to egg allergens would help to identify persistent egg
      allergic children, avoiding unnecessary risky challenges. This study was designed
      to assess the accuracy of a SPT and sIgE levels to egg allergens in order to
      determine persistent egg allergy in IgE-mediated allergic children after an egg
      free diet. METHODS: Children below 16 years were prospectively and consecutively
      recruited. Inclusion criteria were: allergy to egg proteins (children with a
      positive clinical case of IgE-mediated egg allergy and a positive SPT to egg
      allergens and/or positive sIgE levels), and strict egg avoidance diet followed
      for at least 6 months. Clinical histories were recorded and all patients
      underwent SPTs, sIgE levels to egg allergens and the gold standard -a double
      blind placebo-controlled egg challenge (DBPCFG). DBPCFG was interpreted without
      knowledge of the results of the other tests and vice-versa. A SPT and sIgE
      levels' ROC curves analysis was performed to compare the diagnostic performance
      of the different tests. RESULTS: Finally, 157 children were included in the
      study. One hundred out of these 157 children (63.7%) had a positive oral
      challenge. Ninety-six were male (61%), and the median age was 2.5 years. One
      hundred and three (66.9%) had atopic dermatitis. A 7 mm egg white prick test had
      a positive likelihood ratio (+LR) of 6.7, and a level of 1.3 KU/L egg white-sIgE
      had a +LR of 5.1. A 7 mm egg white SPT had a positive predictive value of 92.3%
      (95% CI 85.1-99.5), and for a 9 mm egg white SPT this value was 95.6% (95% CI
      87.3-100.0). For egg white-sIgE, 1.5 KU/L had a positive predictive value of
      90.4% (95% CI 82.4-98.4) and for 25 KU/L it was 100.0% (95% CI 100.0-100.0). SPTs
      with ovotransferrin and lysozyme showed the lowest accuracy, followed by yolk and
      ovalbumin SPTs. CONCLUSION: This study is the first to evaluate both tests (SPT
      and sIgE levels) and all egg allergens to determine the persistence of egg
      allergy in IgE-mediated allergic children. Measuring the SPT and sIgE levels is
      useful to predict persistent allergy in these children, especially with the egg
      white complete extract. An oral challenge should not be performed in egg allergic
      paediatric patients with either an egg white prick test above 7 mm or a white egg
      sIgE determination above 1.3 KU/L, because there is a 90% probability of
      remaining allergic.

PMID- 19594548
TI  - Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma
      from patients with breast carcinoma and high-grade astrocytoma.
AB  - Identification of tumor-derived proteins in the circulation may allow for early
      detection of cancer and evaluation of therapeutic responses. To identify
      circulating tumor-derived proteins, mice were immunized with concentrated culture
      medium conditioned by human breast cancer cells. Antibodies generated by
      hybridomas were screened against conditioned media from both normal epithelial
      cells and tumor cells. Antibody selectively reacting with tumor cell-conditioned
      media was further characterized. This led to the development of a monoclonal
      antibody (Alper-p280) that reacts with a newly identified 280-kDa secreted
      variant of human filamin-A. Circulating filamin-A was detected in patient plasma
      samples using Alper-p280 in an ELISA assay. Human plasma samples from 134
      patients with brain, breast, or ovarian cancer, 15 patients with active
      arthritis, and 76 healthy controls were analyzed. Filamin-A protein levels in
      human cell lines and tissues were analyzed by western blotting,
      immunohistochemistry, and electron and confocal microscopy. Circulating filamin-A
      was detected in the plasma of 109 of 143 patients with breast cancer and primary
      brain tumors. Plasma levels of filamin-A showed 89.5% sensitivity (95% confidence
      interval [CI] = 0.67% to 0.99%) and 97.8% specificity (95% CI = 0.88% to 0.99%)
      for glioblastoma at a cut-off of 21.0 ng/mL. Plasma levels of filamin-A (>36.0
      ng/mL) had 96.7% sensitivity (95% CI = 0.80% to 0.99%) and 67.8% specificity (95%
      CI = 0.54% to 0.79%) for metastatic breast cancer. Filamin-A levels were
      increased in malignant breast or brain tissues, but not in normal control
      tissues. Filamin-A localized to lysosomes in MDA.MB.231 breast cancer cells, but
      not in normal human mammary epithelial cells, suggesting that filamin-A may
      undergo cancer-specific processing. Plasma filamin-A appears to be a specific and
      sensitive marker for patients with high-grade astrocytoma or metastatic breast
      cancer. Additional novel cancer biomarkers have been identified and are being
      developed alongside Alper-p280 for use in diagnosis of breast carcinoma and high
      grade astrocytoma, and for use in the evaluation of therapeutic responses.

PMID- 19594550
TI  - Endoplasmic reticulum stress involved in heart and liver injury in iron-loaded
      rats.
AB  - 1. Iron overload contributes to the pathogenesis of various diseases and directly
      induces tissue injury. In the present study, we investigated the relationship
      between heart and liver injury induced by iron overload and cellular endoplasmic
      reticulum (ER) stress to explore the molecular mechanism of iron overload-induced
      cellular injury. 2. Iron overload in rats was generated by intraperitoneal
      injection of iron-dextran chronically (30 mg/kg per day for 9 weeks) or acutely
      (300 mg/kg once). Tissue injury was assessed by determining serum lactate
      dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) activity, as well as malondialdehyde (MDA) content in the
      heart and liver. The ER stress response was analysed by expression of glucose
      response protein 78 (GRP78) and activation of caspase 12. 3. In chronic iron
      loaded rats, iron levels in the heart and liver were higher, by approximately 2-
      and 7.8-fold, respectively (P < 0.01), compared with control. Serum LDH, ALT and
      AST activity, as well as MDA content, GRP78 expression and caspase 12 activity in
      the heart and liver, were upregulated in chronically iron-loaded rats. In acute
      iron-loaded rats, iron content in the heart and liver was 51% and 63% higher than
      in controls (both P < 0.01). Serum LDH, ALT and AST activity, MDA content in the
      heart and liver and levels of ER stress markers were all increased in acute iron
      loaded rats. N-Acetylcysteine (150 mg/kg, s.c.) lowered the levels of these
      parameters in acute iron-loaded rats. 4. The results of the present study
      indicate that ER stress may play an important role in iron-induced tissue injury
      and that reactive oxygen species may mediate the ER stress response in the
      pathogenesis of iron-overload cellular injury.

PMID- 19594551
TI  - Role of extracellular Na+, Ca2+-activated Cl- channels and BK channels in the
      contraction of Ca2+ store-depleted tracheal smooth muscle.
AB  - 1. In the present study, we investigated the series of events involved in the
      contraction of tracheal smooth muscle induced by the re-addition of Ca(2+) in an
      in vitro experimental model in which Ca(2+) stores had been depleted and their
      refilling had been blocked by thapsigargin. 2. Mean (+/-SEM) contraction was
      diminished by: (i) inhibitors of store-operated calcium channels (SOCC), namely
      100 micromol/L SKF-96365 and 100 micromol/L 1-(2-trifluoromethylphenyl) imidazole
      (to 66.3 +/- 4.4 and 41.3 +/- 5.2% of control, respectively); (ii) inhibitors of
      voltage-gated Ca(2+) channels Ca(V)1.2 channels, namely 1 micromol/L nifedipine
      and 10 micromol/L verapamil (to 86.2 +/- 3.4 and 76.9 +/- 5.9% of control,
      respectively); and (iii) 20 micromol/L niflumic acid, a non-selective inhibitor
      of Ca(2+)-dependent Cl(-) channels (to 41.1 +/- 9.8% of control). In contrast,
      contraction was increased 2.3-fold by 100 nmol/L iberiotoxin, a blocker of the
      large-conductance Ca(2+)-activated K(+) (BK) channels. 3. Furthermore,
      contraction was significantly inhibited when Na(+) in the bathing solution was
      replaced by N-methyl-D-glucamine (NMDG(+)) to 39.9 +/- 7.2% of control, but not
      when it was replaced by Li(+) (114.5 +/- 24.4% of control). In addition, when
      Na(+) had been replaced by NMDG(+), contractions were further inhibited by both
      nifedipine and niflumic acid (to 3.0 +/- 1.8 and 24.4 +/- 8.1% of control,
      respectively). Nifedipine also reduced contractions when Na(+) had been replaced
      by Li(+) (to 10.7 +/- 3.4% to control), the niflumic acid had no effect (116.0 +/
      4.5% of control). 4. In conclusion, the data of the present study demonstrate
      the roles of SOCC, BK channels and Ca(V)1.2 channels in the contractions induced
      by the re-addition of Ca(2+) to the solution bathing guinea-pig tracheal rings
      under conditions of Ca(2+)-depleted sarcoplasmic reticulum and inhibition of
      sarcoplasmic/endoplasmic reticulum calcium ATPase. The contractions were highly
      dependent on extracellular Na(+), suggesting a role for SOCC in mediating the
      Na(+) influx.

PMID- 19594552
TI  - Regional differences in the modulatory role of the epithelium in sheep airway.
AB  - 1. The airway epithelium may modulate smooth muscle responsiveness via the
      release of biologically active substances, such as nitric oxide (NO) and
      prostaglandins. Based on regional differences in structure and function described
      for the airway epithelium, we performed a comparative study on the responsiveness
      of sheep isolated, epithelium-intact or -denuded, first- to fourth-order bronchi
      to acetylcholine (ACh). 2. We performed contractility studies using KCl or
      cholinergic stimuli in the presence or absence of NO or prostaglandin-related
      drugs in epithelium-intact and epithelium-denuded bronchial strips obtained from
      all four airway regions. We also studied the expression of NO synthase (NOS),
      using the NADPH-diaphorase staining technique, and the effect of airway
      epithelium removal on the synthesis of NO metabolites in the different bronchi
      orders. 3. There was no difference in the response of first- to fourth-order
      epithelium-intact bronchi to ACh (1 nmol/L-100 mmol/L) or KCl (5-100 mmol/L).
      Removal of the epithelium had no effect on ACh-induced contractions of first- and
      second-order bronchi, but increased responses of third- and fourth-order bronchi
      to ACh. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (100
      micromol/L) increased ACh-induced contractions of fourth-order epithelium-intact
      bronchi only. The NO donor sodium nitroprusside (1 nmol/L-1 mmol/L) equally
      relaxed 1 micromol/L carbachol-precontracted epithelium-denuded first- and fourth
      order bronchi. 4. Although NAPDH-diaphorase staining demonstrated no regional
      differences in NOS expression, basal levels of NO metabolites were 4.5-fold
      greater in fourth- compared with second-order epithelium-intact bronchi. 5. The
      cyclo-oxygenase inhibitor indomethacin (10 micromol/L) had no effect on ACh
      induced contractions of first- to fourth-order epithelium-intact bronchi, but
      decreased responses of fourth-order epithelium-denuded bronchi to ACh. The
      contractile effect of the thromboxane A(2) mimetic U-46619 (1 nmol/L-10
      micromol/L) was greater in fourth- compared with first-order epithelium-denuded
      bronchi. 6. In conclusion, the sheep airway epithelium exhibits regional
      differences in its modulatory role and this is particularly apparent in small
      bronchi.

PMID- 19594553
TI  - Age-related synaptic changes in the CA1 stratum radiatum and spatial learning
      impairment in rats.
AB  - 1. Age-related impairments in hippocampus-dependent spatial learning and memory
      are not associated with a loss of neurons, but may be related to synaptic
      changes. In the present study, we analysed the behavioural performance of adult,
      middle-aged and old Wistar rats using the Morris water maze, as well as the
      structure of synapses and the expression of autophosphorylated Ca(2+)/calmodulin
      dependent protein kinase II at threonine 286 (pThr286-alphaCaMKII), a key post
      synaptic protein in the CA1 stratum radiatum, in the same rats. 2. Old Wistar
      rats showed significant cognitive deficits. Synaptic density, the area of post
      synaptic densities and the total number of synapses in the CA1 stratum radiatum
      of old rats were significantly decreased compared with adult rats. The decrease
      in autophosphorylated pThr286-alphaCaMKII was age dependent. 3. These findings
      reveal that age-related impairments in learning and memory are associated with
      synaptic atrophy. The decreased expression of pThr286-CaMKII may result in
      reduced synaptic function with ageing.

PMID- 19594554
TI  - Podocyte injury is suppressed by 1,25-dihydroxyvitamin D via modulation of
      transforming growth factor-beta 1/bone morphogenetic protein-7 signalling in
      puromycin aminonucleoside nephropathy rats.
AB  - 1. Accumulating evidence suggests that vitamin D and its analogues are
      renoprotective. However, the precise mechanisms and the molecular targets by
      which active vitamin D exerts its beneficial effects remain obscure. The
      objective of the present study was to evaluate the effect of active vitamin D on
      rats with puromycin aminonucleoside (PAN) nephropathy, a model that is
      characterized by predominant podocyte injury. 2. The PAN nephropathy rats were
      created by a single intravenous injection of 100 mg/kg PAN. Changes in renal
      pathology and podocyte numbers were observed. Real-time polymerase chain reaction
      (PCR) was performed to examine mRNA expression of nephrin, transforming growth
      factor (TGF)-beta1 and bone morphogenetic protein (BMP)-7. Protein expression of
      nephrin, TGF-beta1, BMP-7 and p-Smad2/3 and p-Smad1/5/8 was examined by
      immunofluorescence, immunohistochemistry and western blotting, respectively. Rats
      were treated with 1,25(OH)(2)D(3) by gastric gavage at a dose of 2.5 microg/kg
      per day, starting 2 days before PAN injection and continuing throughout the
      experiment. 3. A single injection of PAN induced massive proteinuria and elevated
      serum creatinine on Day 7, both of which were significantly suppressed by 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Immunofluorescence and real-time PCR of
      the podocyte-associated protein nephrin revealed reduced and discontinuous
      staining and this change was reversed by 1,25(OH)(2)D(3). In PAN nephropathy
      rats, TGF-beta1 and p-Smad2/3 expression was upregulated, whereas that of BMP-7
      and p-Smad1/5/8 was downregulated. Treatment with 1,25(OH)(2)D(3) significantly
      restored BMP-7/Smad signalling while suppressing TGF-beta1/Smad signalling. 4. In
      conclusion, 1,25(OH)(2)D(3) can ameliorate podocyte damage and proteinuria
      induced by PAN. The beneficial effects of 1,25(OH)(2)D(3) on podocytes may be
      attributable, in part, to direct modulation of TGF-beta1/BMP-7 signalling.

PMID- 19594555
TI  - Smoking and coronary atherosclerosis: follow-up study in China.
AB  - 1. The aim of the present study was to explore the association between the total
      number of cigarettes smoked in life and the severity of and mortality due to
      coronary atherosclerosis. 2. The study population comprised 1096 consecutive
      patients (820 men and 276 women) who underwent coronary angiography for suspected
      or known coronary atherosclerosis. Anthropometric and plasma measurements (body
      mass index, blood pressure and blood lipid, blood glucose and pro-insulin levels)
      were made. The number of cigarettes smoked during previous years was estimated.
      The severity of coronary atherosclerosis was defined by the Gensini score system.
      3. At baseline, a significant positive association was observed between the
      number of cigarettes smoked and Gensini score (r = 0.213; P = 0.000), pro-insulin
      (r = 0.072; P = 0.017), total leucocyte count (r = 0.179; P = 0.000) and
      neutrophil count (r = 0.164; P = 0.000), whereas an inverse correlation was found
      between the number of cigarettes smoked and High-density lipoprotein-cholesterol
      (r = -0.150; P = 0.000). 4. When participants were divided into five categories
      based on the baseline number of cigarettes smoked, an independent association
      between baseline number of cigarettes smoked and all-cause mortality was observed
      in a multivariate analysis of Cox proportional hazards models, with a hazard
      ratio (95% confidence interval) of 1.328 (1.086-1.623; P = 0.006) during a median
      follow up of 2.86 years. 5. The number of cigarettes smoked was a highly
      significant predictor of coronary atherosclerosis and an independent risk factor
      for mortality in subjects with atherosclerosis in this Chinese population.

PMID- 19594556
TI  - Protective effects of leonurine in neonatal rat hypoxic cardiomyocytes and rat
      infarcted heart.
AB  - 1. Previous studies have shown that extracts of Herba leonuri, predominantly
      containing the phytochemical components leonurine and stachydrine, provide
      protective effects in the ischaemic myocardium by acting as free radical
      scavengers and inhibiting the formation of reactive oxygen species. 2. The
      present study was designed to investigate the cardioprotective effects of 10(-6)
      mol/L leonurine on neonatal rat cardiomyocytes treated with hypoxia plus serum
      deprivation, a component of ischaemia, and to determine the mechanisms underlying
      the protective effects with regard to cardiac anti-oxidant enzymes and apoptosis
      genes. Cardiomyocytes were treated with leonurine 8 h prior to exposure to
      hypoxia. In addition, we investigated the effects of 7.5 and 15 mg/kg leonurine,
      administered to rats i.p. for 7 days prior to left coronary artery ligation, on
      subsequent infarct size of the ischaemic heart. 3. Leonurine significantly
      increased the viability of cardiomyocytes injured by hypoxia. In the leonurine
      treated group, gene expression levels of pro-apoptotic genes, namely Bax and Fas,
      were significantly downregulated (by 0.95- and 0.72-fold, respectively; P <
      0.001) compared with the hypoxic control group, whereas the expression of Bcl-2
      and Bcl-xl was upregulated following leonurine treatment (by 1.03- and 1.07-fold,
      respectively; P < 0.05). Correspondingly, leonurine treatment increased Bcl-2
      protein levels and decreased Bax protein levels. Assays investigating cardiac
      anti-oxidant enzymes provided further evidence for a protective effect of
      leonurine, as indicated by the induction of the anti-oxidant enzymes superoxide
      dismutase and catalase. Furthermore, leonurine decreased infarct size in
      ischaemic rat heart. 4. The results of the present study suggest that the
      mechanisms of action of leonurine in hypoxic neonatal rat cardiomyocytes and
      infarcted rat heart may be related to its anti-oxidant and anti-apoptotic
      properties.

PMID- 19594557
TI  - Treatment of chronic uveitic cystoid macular oedema.

PMID- 19594558
TI  - In vivo confocal microscopy of the bulbar conjunctiva.
AB  - BACKGROUND: The aim of this work is to develop a more complete qualitative and
      quantitative understanding of the in vivo histology of the human bulbar
      conjunctiva. METHODS: Laser scanning confocal microscopy (LSCM) was used to
      observe and measure morphological characteristics of the bulbar conjunctiva of 11
      healthy human volunteer subjects. RESULTS: The superficial epithelial layer of
      the bulbar conjunctiva is seen as a mass of small cell nuclei. Cell borders are
      sometimes visible. The light grey borders of basal epithelial cells are clearly
      visible, but nuclei can not be seen. The conjunctival stroma is comprised of a
      dense meshwork of white fibres, through which traverse blood vessels containing
      cellular elements. Orifices at the epithelial surface may represent goblet cells
      that have opened and expelled their contents. Goblet cells are also observed in
      the deeper epithelial layers, as well as conjunctival microcysts and mature forms
      of Langerhans cells. The bulbar conjunctiva has a mean thickness of 32.9 +/- 1.1
      microm, and a superficial and basal epithelial cell density of 2212 +/- 782 and
      2368 +/- 741 cells/mm(2), respectively. Overall goblet and mature Langerhans cell
      densities are 111 +/- 58 and 23 +/- 25 cells/mm(2), respectively. CONCLUSIONS:
      LSCM is a powerful technique for studying the human bulbar conjunctiva in vivo
      and quantifying key aspects of cell morphology. The observations presented here
      may serve as a useful marker against which changes in conjunctival morphology due
      to disease, surgery, drug therapy or contact lens wear can be assessed.

PMID- 19594559
TI  - High-definition imaging of trabeculectomy blebs using spectral domain optical
      coherence tomography adapted for the anterior segment.
AB  - BACKGROUND: The aim of this work was to image trabeculectomy blebs using spectral
      domain optical coherence tomography (SDOCT). METHODS: In this prospective cross
      sectional study, patients who had undergone trabeculectomy with at least 3 months
      of follow up were included. Blebs were imaged using an adapted SDOCT system
      (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA) and time domain
      anterior segment optical coherence tomography (ASOCT) (Visante OCT, Carl Zeiss
      Meditec Inc.). An observer masked to clinical data assessed the utility of SDOCT
      and ASOCT in visualizing structures in successful and failed blebs. RESULTS:
      Fifty-one eyes were imaged, of which 43 (84.3%) were successful. SDOCT showed
      wall thickening (93.0% vs. 67.4%, P = 0.006) and discrete hyporeflective spaces
      in the wall (88.4% vs. 14.0%, P < 0.0001) in a greater proportion of successful
      blebs than ASOCT. SDOCT showed the bleb cavity (23.3% vs. 48.8%, P = 0.02),
      scleral flap (34.9% vs. 90.7%, P < 0.0001), subflap space (20.9% vs. 72.1%, P <
      0.0001) and ostium (9.3% vs. 88.4%, P < 0.0001) in fewer successful blebs than
      ASOCT. The internal ostium was not visualized in any failed bleb using SDOCT,
      whereas ASOCT showed the ostium in 87.5% of failed blebs (P = 0.001). SDOCT
      showed cystic spaces in the bleb wall in a greater proportion of successful blebs
      than failed blebs (88.4% vs. 37.5%, P = 0.005). CONCLUSIONS: SDOCT imaging was
      able to show fine superficial features in the bleb wall. However, SDOCT had
      limited clinical utility in that it did not provide useful information about deep
      features such as flap position, bleb cavity formation or patency of the subflap
      space and internal ostium.

PMID- 19594560
TI  - Mitomycin-C as adjuvant therapy in the treatment of sebaceous gland carcinoma in
      high-risk locations.
AB  - PURPOSE: To report on the use of Mitomycin-C as adjuvant therapy to excision and
      cryotherapy in patients with sebaceous gland carcinoma (SGC) in high-risk
      locations. DESIGN: Retrospective, consecutive, case series. PARTICIPANTS: Three
      patients with SGC of the upper palpebral conjunctiva or caruncle, but without
      clinical pagetoid spread. METHODS: Following excision and double freeze-thaw
      cryotherapy, patients with histology demonstrating SGC of the ocular surface were
      treated with topical Mitomycin-C (0.04%). Follow-up was conducted over an average
      of 30 months (range: 24-37 months). MAIN OUTCOME MEASURES: Postoperative evidence
      of local recurrence, lymph node or distant organ metastasis. RESULTS: No patients
      had evidence of local recurrence or systemic disease. CONCLUSIONS: Wide surgical
      excision with cryotherapy is the basis of treatment of SGC without pagetoid
      spread. The use of Mitomycin-C as adjuvant therapy remains controversial,
      although there is some rationale for its use in high-risk situations.

PMID- 19594561
TI  - The diameter of the nasolacrimal canal measured by computed tomography: gender
      and racial differences.
AB  - BACKGROUND: The incidence of dacryocystorhinostomy surgery among Pacific People
      is greater than would be expected given their proportion in the population. Some
      have suggested that racial and sex differences in facial skull dimensions produce
      narrower nasolacrimal canals and therefore differences in the incidence of
      primary acquired nasolacrimal duct obstruction (PANDO). We measured the minimum
      diameter of the canal in those not known to have PANDO. METHOD: A retrospective
      review of the digital computed tomography (CT) database was performed. Minimum
      diameter of the nasolacrimal canal on axial cuts of a sinus series CT scan was
      measured. Sex and racial origin were recorded. All series on the database were
      included. Absence of axial images and pathology distorting the canal excluded a
      patient. This was carried out in the Department of Radiology and Ophthalmology,
      Greenlane Medical Centre, Auckland. RESULTS: A total of 178 CT scans were
      included. Men had a mean diameter of 3.9 mm (95% confidence interval [95%CI]: 3.8
      4.1) versus women 3.6 mm (95%CI: 3.5-3.8) P = 0.01. Both Caucasian and New
      Zealand Maori had mean diameters of 3.7 mm (95%CI: 3.5-3.9) whereas Pacific
      People were 4.1 mm (95%CI: 3.9-4.3) P = 0.01. CONCLUSIONS: As in other studies
      women had narrower canals than men. Surprisingly we found no difference between
      New Zealand Maori and Caucasian. Unexpected was the larger diameter in Pacific
      People, as they have a higher incidence of dacryocystorhinostomy surgery. PANDO
      is likely to be of multifactorial aetiology and nasolacrimal canal diameter may
      not be a significant factor. Our described method of measuring canal diameter by
      CT scan is comparable to a cadaver study.

PMID- 19594563
TI  - To investigate the prevalence of polypoidal choroidal vasculopathy in presumed
      age-related peripapillary subretinal neovascular membranes.
AB  - BACKGROUND: To investigate the prevalence and angiographic appearances of
      polypoidal choroidal vasculopathy (PCV) masquerading as age-related peripapillary
      subretinal neovascular membranes (PSRNVM). METHODS: A consecutive case series of
      all patients investigated for presumed age-related PSRNVM in our tertiary
      referral centre over the period September 2006-2007. The presenting clinical
      features and fundus fluorescein angiographic (FFA) characteristics of each
      patient's lesion were identified. Any accompanying Indocyanine Green Angiogram
      (ICGA) was also reviewed, and on the basis of this investigation patients were
      classified into one of three groups: proven PCV, probable PCV and PSRNVM.
      RESULTS: Thirty patients with presumed age-related PSRNVM were identified. The
      FFA leakage pattern was occult in 21 patients and classic in nine patients.
      Sixteen patients also had ICGA performed. In 14 of these patients the original
      FFA leakage pattern was occult, and in two it was classic. Of the 14 patients
      with occult leakage on FFA who subsequently underwent ICGA all were found to have
      PCV. CONCLUSIONS: PCV is important and underrecognized in presumed age-related
      PSRNVMs. In such cases, particularly when the pattern of leakage on the
      fluorescein angiogram is occult, ICGA should be performed to identify the site of
      the polyps and if required to direct treatment.

PMID- 19594562
TI  - Prevalence and risk factors of ocular trauma in an urban south-east Asian
      population: the Singapore Malay Eye Study.
AB  - PURPOSE: To describe the prevalence and risk factors of ocular trauma in an urban
      Asian population. METHODS: A population-based survey of 3280 (78.7% response
      rate) Malay people aged 40-80 years residing in Singapore was conducted in 2004
      2006. Interviewer-administered questionnaire was used to ascertain a history of
      ocular trauma, defined as any eye injury requiring medical attention from a
      doctor. RESULTS: Of the 3264 participants, 149 (5.0%, 95% confidence intervals
      [CI] 4.1-6.0%) reported a history of ocular trauma. Of those, 30.2% had trauma
      from a blunt object, 33.6% from a sharp object, and 22.1% from chemical burns.
      After adjusting for age and sex, men had a higher prevalence of ocular trauma
      than women (8.3% vs. 2.1%, age-adjusted odds ratio [OR] 4.7, CI 3.1-7.1), and
      younger persons had a higher risk of ocular trauma (per year increase in age, OR
      0.98, CI 0.96-0.99). Consumption of alcohol was associated with higher likelihood
      of having ocular injury (OR 4.3, CI 2.2-8.4). CONCLUSIONS: One in 20 persons in
      this urban south-east Asian population had a history of ocular trauma. Younger
      persons, men and consumption of alcohol were risk factors for ocular trauma.

PMID- 19594564
TI  - A study of macular hole formation by serial spectral optical coherence
      tomography.
AB  - BACKGROUND: The purpose of this paper is to evaluate changes of the vitreoretinal
      interface in fellow eyes of eyes with a macular hole and to study early stages of
      macular hole formation by spectral optical coherence tomography (SOCT). METHODS:
      A prospective study of 131 consecutive patients with history of macular hole.
      Serial SOCT examinations were performed on the fellow eyes four times during a 6
      month observation period. Progression of foveal changes and formation of macular
      hole in the fellow eyes were studied. RESULTS: Seven distinct abnormalities in
      the foveal region were noted in 70 of the fellow eyes (53.4%). Additionally in 18
      patients (13.6%) other defects typical for the older population were noted.
      Gradual evolution to full-thickness macular holes during the 6-month observation
      period was noted in five eyes. One of these eyes had a previously detected cyst,
      and four eyes had elevation of the photoreceptor layer. CONCLUSIONS: The high
      prevalence of macular abnormalities in the fellow eyes particularly epiretinal
      membranes and vitreous traction with schizis as well as the evolution of these
      abnormalities over time suggest that diseases of the vitreomacular interface may
      have similar pathogenesis. Macular hole formation often starts as a triangular
      elevation of the photoreceptor layer. In some cases, a cyst in the inner retinal
      layers can be an early step in macular hole formation.

PMID- 19594565
TI  - Submacular haemorrhage after intravitreal bevacizumab compared with intravitreal
      ranibizumab in large occult choroidal neovascularization.
AB  - BACKGROUND: Submacular haemorrhage may occur following intravitreal bevacizumab
      injection for large occult choroidal neovascularization (CNV) in age-related
      macular degeneration (AMD). We report the occurrence of submacular haemorrhage
      following intravitreal ranibizumab compared with intravitreal bevacizumab for
      large occult CNV in AMD. METHODS: Retrospective, comparative evaluation of two
      interventional case series. Evaluation of consecutive patients with occult CNV >
      or = 15 mm(2) treated with intravitreal bevacizumab (n = 14) and intravitreal
      ranibizumab (n = 22) over a 2-year period within a single institution.
      Postoperative submacular haemorrhage, Early Treatment Diabetic Retinopathy Study
      derived visual acuity, preoperative blood pressure and anticoagulant use were
      noted. The two groups were compared using Fisher's exact test. RESULTS: The mean
      surface area of occult CNV at presentation was 20.9 +/- 5.4 mm(2) in the
      bevacizumab group and 24.0 +/- 11.0 mm(2) in the ranibizumab group. Fresh
      submacular haemorrhage was seen in 4 out of 14 patients following bevacizumab
      compared with 0 out of 22 patients following ranibizumab (P = 0.017, odds ratio =
      19.29). Mean preoperative blood pressures were very similar between the groups.
      28.6% of patients in the bevacizumab group were on oral anticoagulants compared
      with 31.8% in the ranibizumab group. None of the patients who developed
      postoperative haemorrhage were on anticoagulants. CONCLUSIONS: Acute submacular
      haemorrhages appear to be a significant adverse event following intravitreal
      bevacizumab in occult CNV > or = 15 mm(2). Intravitreal ranibizumab appears to
      have a significantly lower incidence of postoperative submacular haemorrhage in
      occult CNV > or = 15 mm(2). Larger studies are required to identify the most
      appropriate agent for the treatment of large occult CNV.

PMID- 19594566
TI  - Intravitreal triamcinolone for persistent cystoid macular oedema in eyes with
      quiescent uveitis.
AB  - BACKGROUND: To determine the outcome following injections of triamcinolone
      acetate (IVTA) in the treatment of persistent cystoid macular oedema (CMO) in
      quiescent, non-infectious uveitis. METHODS: Retrospective analysis of patients
      with inactive uveitis requiring/not requiring immunosuppressive therapy who
      received IVTA because of chronic CMO refractory to previous systemic steroids.
      Number of IVTA (re-)treatments, distance visual acuity, near visual acuity, mean
      foveal thickness, intraocular pressure, duration of CMO, type of uveitis and
      systemic therapy were assessed previous to and 1, 4, 12 weeks following each IVTA
      treatment. RESULTS: Between March 2003 and May 2006, 24 eyes of 18 patients
      received between one and three IVTA injections. A resolution of chronic CMO was
      observed in 7/24 eyes (29.2%, 5 eyes after single injection of IVTA, 1 eye each
      after two and three injections of IVTA), a significant increase in distance
      visual acuity in 9/24 eyes (37.5%; 5 eyes with resolution of CMO, 4 eyes despite
      persistent CMO) and in near visual acuity in 13/24 eyes (54.6%; 6 eyes with
      resolution of CMO, 7 eyes despite persistent CMO). CONCLUSIONS: IVTA might be
      considered as a treatment for patients with chronic CMO when persistent despite
      previous systemic steroid therapy. Even patients without sustained resolution of
      CMO after IVTA might benefit in terms of transiently increasing visual acuity,
      but progression of cataract and rise in intraocular pressure limit repeatability.

PMID- 19594567
TI  - Comparison of the corneal endothelial protective effects of Healon-D and Viscoat.
AB  - BACKGROUND: The use of dispersive ophthalmic viscosurgical devices (OVDs) has
      been shown to provide significant protection against air bubble damage to the
      corneal endothelium when compared with cohesive OVDs. We compared the corneal
      endothelial protective effects of a new dispersive OVD, Healon-D, with Viscoat.
      METHODS: Healon-D and Viscoat were used in a randomized and masked fashion in the
      anterior chamber of 40 rabbit eyes during a procedure where ultrasound at 70%
      continuous energy was delivered for 2 min. Two millilitres of air bubbles were
      injected into the anterior chamber during the first minute of the procedure on
      each eye. Corneas were then stained with trypan blue and alizarin red and
      evaluated via light microscopy for endothelial injury. Both denuding of the
      endothelial layer, as well as damage to endothelial cells were quantified by
      using the Evaluation of Posterior Capsule Opacification digital imaging system.
      RESULTS: The denuded area for eyes treated with Healon-D and Viscoat were not
      significantly different (medians of 0.004167and 0.003333, respectively, P =
      0.8908). There was no significant difference in the area of endothelial cell
      damaged (medians of 0.02183 and 0.01433, respectively, P = 0.4565). When the
      denuded and damaged areas were calculated together, there was also no difference
      in the total injured area (medians of 0.05817 and 0.05821, respectively, P =
      0.5740). CONCLUSION: The new dispersive OVD Healon-D is equally as effective as
      Viscoat in protecting the corneal endothelial layer from denuding and damage from
      air bubbles during anterior segment surgery.

PMID- 19594568
TI  - Ascorbic acid concentration is reduced in the secondary aqueous humour of
      glaucomatous patients.
AB  - BACKGROUND: We aimed to evaluate the ascorbic acid concentration in secondary
      aqueous humour (AH) from glaucomatous patients and to compare it with primary AH
      from primary open-angle glaucoma patients and non-glaucomatous patients. METHODS:
      Primary AH samples were prospectively obtained from clinically uncontrolled
      primary open-angle glaucoma patients and senile cataract patients (controls)
      prior to trabeculectomy and cataract surgery. Secondary AH samples were obtained
      from eyes with previous intraocular surgery, prior to trabeculectomy or cataract
      surgery. AH (0.1 mL) was aspirated by inserting a 26-gauge needle into the
      anterior chamber just before surgery and then immediately stored at -80 degrees
      C. The ascorbic acid concentration was determined in a masked fashion by high
      pressure liquid chromatography. RESULTS: A total of 18 patients with senile
      cataract, 16 glaucomatous patients with primary AH (no previous intraocular
      surgery) and 11 glaucomatous patients with secondary AH (previous intraocular
      surgery) were included. There was no difference in mean age between groups (P =
      0.15). The mean +/- standard deviation concentration of ascorbic acid in the
      secondary AH from glaucomatous patients (504 +/- 213 micromol/L [95% confidence
      interval {CI}, 383-624]) was significantly lower than the concentration of
      ascorbic acid found in the primary aqueous of primary open-angle glaucoma (919 +/
      427 micromol/L [95% CI, 709-1128]) and control patients (1049 +/- 433 micromol/L
      [95% CI, 848-1249]; P < 0.01, Kruskal-Wallis test). CONCLUSIONS: The ascorbic
      acid concentration in secondary AH of glaucomatous patients was approximately
      twofold lower in comparison with primary AH of glaucomatous and cataract
      patients. The implications of a reduced concentration of ascorbic acid in the
      secondary AH deserve further investigation.

PMID- 19594569
TI  - Accessory levator muscle slips of the levator palpebrae superioris muscle.
AB  - BACKGROUND: Accessory levator muscle slips may be associated with congenital
      eyelid retraction or blepharoptosis. Nevertheless, congenital retraction of the
      upper eyelid is a poorly defined entity about which little is known. Because of
      the clinical importance of the accessory levator muscle slip of the levator
      palpebrae superioris muscle, this study aimed to describe the morphological
      appearance of this variation in human adult orbits. METHODS: This study was
      undertaken in 60 orbits of 30 embalmed adult human cadavers, 17 men and 13 women,
      between the ages of 38 and 87 years at death. All cadavers were embalmed in 4%
      formalin solution. RESULTS: Three accessory levator muscle slips of the levator
      palpebrae superioris muscle were identified. One of these arose laterally from
      the origin of the levator palpebrae superioris muscle. At its anterior end, it
      divided into two parts, the main superior and a smaller inferior accessory. The
      second had an accessory levator fibromuscular slip. It arose medially from the
      origin of the levator palpebrae superioris and lost its muscular character after
      a short course. The third arose from the origin of the levator palpebrae
      superioris as a thin flat muscle. CONCLUSIONS: Although many variations of the
      levator palpebrae superioris muscle have been reported in fetuses, investigation
      and demonstration of these may be more important in children and adults for
      ophthalmic surgery. We believe that detailed knowledge regarding the
      morphological appearance of an accessory levator muscle slip of the levator
      palpebrae superioris muscle may be useful for successful outcomes in ophthalmic
      surgery.

PMID- 19594570
TI  - Kimura disease of the eyelid in an Indian man.
AB  - Kimura disease is a rare idiopathic chronic inflammatory disease, characterized
      by subcutaneous nodular lesions in the head and neck area. Ophthalmic
      manifestation of Kimura disease involves orbital and eyelid lesions mostly in
      Asian patients, but it has been described in White patients and Black Caribbean
      patients. Kimura disease is usually associated with eosinophilia and occasionally
      with renal disease. Here, we report a case of Kimura disease of the eyelid in a
      50-year-old Indian man with eosinophilia. The main differential diagnosis was
      angiolymphoid hyperplasia with eosinophilia. Histology is crucial to separate
      these two entities, and our case was shown to be Kimura disease by histology. To
      our knowledge, this is the first report of a person of Indian origin to develop
      Kimura disease involving the eyelid.

PMID- 19594571
TI  - Excessive granulation tissue at the harvest site following pterygium surgery with
      conjunctival autograft: a clinicopathological case report.
AB  - A 31-year-old woman had an uneventful primary pterygium surgery with a
      conjunctival autograft. Four days following the surgery a red-violet-coloured
      lesion appeared at the bare autograft harvest site that was excised at
      postoperative 1 month leaving the autograft site bare again. The lesion recurred
      in a week. The excision was repeated but this time the sclera was closed by end
      to-end suturation of conjunctiva. The lesion did not recur during the 3 months of
      follow up. Pathological examination revealed the lesion to be composed of
      granulation tissue composed of an overlying stratified epithelium and underlying
      marked vascularization, fibroblasts and lymphomonocyte cells. Excessive
      granulation tissue may form when there is a deviation in wound healing. Removal
      of the excessive granulation and restoration of the continuity of the surrounding
      epithelium should be curative.

PMID- 19594572
TI  - Case of post Descemet stripping endothelial keratoplasty retrocorneal fibrous
      membrane.

PMID- 19594574
TI  - Combined residency and doctoral programme in ophthalmology: a tool for the
      education of clinical scientists.

PMID- 19594573
TI  - Cosmetic contact lens-related Acanthamoeba keratitis.

PMID- 19594575
TI  - Are failure rates of primary trabeculectomy really increasing?

PMID- 19594579
TI  - Calling New Zealand: why do we travel? - response.

PMID- 19594581
TI  - Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic
      differentiation.
AB  - INTRODUCTION: In vitro expansion and differentiation of mesenchymal stem cells
      (MSC) rely on specific environmental conditions, and investigations have
      demonstrated that one crucial factor is oxygen environment. OBJECTIVES: In order
      to understand the impact of oxygen tension on MSC culture and chondrogenic
      differentiation in vitro, we developed a mathematical model of these processes
      and applied it in predicting optimal assays. METHODS AND RESULTS: We compared
      ovine MSCs under physiologically low and atmospheric oxygen tension. Low oxygen
      tension improved their in vitro population growth as demonstrated by monoclonal
      expansion and colony forming assays. Moreover, it accelerated induction of the
      chondrogenic phenotype in subsequent three-dimensional differentiation cultures.
      We introduced a hybrid stochastic multiscale model of MSC organization in vitro.
      The model assumes that cell adaptation to non-physiological high oxygen tension
      reversibly changes the structure of MSC populations with respect to
      differentiation. In simulation series, we demonstrated that these changes
      profoundly affect chondrogenic potential of the populations. Our mathematical
      model provides a consistent explanation of our experimental findings.
      CONCLUSIONS: Our approach provides new insights into organization of MSC
      populations in vitro. The results suggest that MSC differentiation is largely
      reversible and that lineage plasticity is restricted to stem cells and early
      progenitors. The model predicts a significant impact of short-term low oxygen
      treatment on MSC differentiation and optimal chondrogenic differentiation at 10
      11% pO(2).

PMID- 19594586
TI  - Proceedings of the 12th Clinicopathological Conference on Renal Allograft
      Pathology, 19 July 2008, Tokyo, Japan. Introduction.

PMID- 19594585
TI  - Salvage transplantation for stage IVa hepatocellular carcinoma, what are the
      guidelines?

PMID- 19594587
TI  - Screening of vesicoureteral reflux in pediatric patients with kidney
      transplantation showing non-specific interstitial fibrosis and tubular atrophy
      with interstitial Tamm-Horsfall protein deposits in protocol allograft biopsy.
AB  - Interstitial fibrosis and tubular atrophy (IF/TA) in kidney allografts are
      induced by multiple factors, and although much effort has been devoted on the
      classification of IF/TA, clarification of the causes of non-specific IF/TA is
      equally important for appropriate therapy. Tamm-Horsfall protein (THP) in renal
      tissue can be a useful marker for the histological expression of urine backflow
      and suspected vesicoureteral reflux (VUR). Here, we examined the presence of VUR
      in pediatric recipients with interstitial THP deposits in kidney allografts to
      clarify the cause of non-specific IF/TA. Ten pediatric patients showing
      interstitial THP deposits with non-specific IF/TA were enrolled and voiding
      cystourethrography was performed. Major histological findings of these patients
      were interstitial mononuclear cell infiltration and fibrosis associated with
      interstitial THP deposits. The semiquantitative grading scores of IF/TA were as
      follows: (i) mild IF/TA (n = 3); (ii) moderate IF/TA (n = 3); and (iii) severe
      IF/TA (n = 4). In the severe grade, diffuse interstitial mononuclear cell
      infiltrates were prominent with the appearance of thyroidization classically
      observed in chronic pyelonephritis. Eight of ten patients (80%) had VUR into the
      graft. Although symptomatic pyelonephritis was not observed in any of the
      patients, asymptomatic bacteriuria was detected in 40.0% of the patients. There
      was no significant correlation between VUR grade and IF/TA histological score.
      The patients without VUR also showed mild or severe IF/TA. Therefore, VUR and
      urinary flow stasis accompanied by asymptomatic urinary tract infection appear to
      be the causes of interstitial mononuclear cell infiltration and fibrosis
      associated with interstitial THP deposits in kidney allografts.

PMID- 19594588
TI  - Thyroidization in renal allografts.
AB  - Thyroidization (thyroid-like appearance) in renal tissue which is made up of a
      colloid-like hyaline cast formation of Tamm-Horsfall glycoprotein (THP) is a
      common finding in chronic pyelonephritis and obstructive nephropathy. This type
      of pathological change is sometimes observed in renal allograft specimens. We
      examined allograft specimens for thyroidization and other pathological findings
      related to thyroidization to characterize the conditions causing such changes.
      One-hundred three patients who underwent renal transplantation between January
      2006 and April 2008 at Gifu University Hospital (251 renal allograft biopsy
      specimens) were enrolled in this study. Sixteen patients had thyroidization (11
      mild, 4 moderate, and 1 severe). In four patients, THP reflux on Bowman's capsule
      was found, and in three patients interstitial THP deposits were observed. In four
      patients, tubulointerstitial nephritis was diagnosed. Fifteen of 16 patients were
      examined for vesicoureteral reflux (VUR) with voiding cystourethrography. Three
      of 15 patients had VUR. In the past medical histories of the 16 patients with
      thyroidization, three had low capacity bladders, two had prostate diseases, and
      six had previous urinary tract infections. In cases of thyroidization with
      additional findings, including THP reflux into Bowman's space and interstitial
      THP deposits, we need to examine the patients for the presence of urinary tract
      diseases. In cases of thyroidization and tubulointerstitial nephritis urinary
      tract infections were suspected. Such subclinical urological diseases in the
      grafts might affect the prognosis of renal function. Therefore, appropriate
      management of urinary tract diseases is required.

PMID- 19594589
TI  - Clinicopathologic evaluation of short-term outcome after early corticosteroid
      discontinuation in kidney transplantation.
AB  - OBJECTIVES: Steroids have been a gold-standard drug of immunosuppressive regimens
      in kidney transplantation. Steroid minimization protocols have been applied to
      minimize the adverse effects of steroids. We have evaluated the short-term
      outcomes of our early steroid discontinuation regimen. METHODS: A total of 128
      recipients who received kidney from ABO-compatible, flow crossmatch-negative
      living-related donors were included in this study. Immunosuppressive regimens
      consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), and basiliximab. In a
      cohort of recipients, designated as a steroid early discontinuation (ESD) group,
      only three doses of methylprednisolone (MP) were given (500, 250, 125 mg). In the
      other cohort of recipients, designated as a chronic steroid (CS) group, MP was
      given chronically, being tapered to 4 mg at one month post-transplant. TAC and
      mycophenolic acid (MPA) blood levels were monitored. The following data were
      retrospectively compared between the two groups at 1, 3, 6, 9, 12 months post
      transplant: serum creatinine (sCr), urine protein per gCr (uP/Cr), the incidence
      of biopsy-proven acute rejection (BPAR), graft survival (GS), area-under-the
      curve of blood levels of tacrolimus (TAC-AUC(0-12), ng h/mL) and mycophenolic
      acid (MPA-AUC(0-12), mug h/mL), MMF dose (mg), the incidence of opportunistic
      infection, post-transplant diabetes mellitus (PTDM), and histopathologic findings
      of protocol biopsy according to the Banff '07 classification. RESULTS: sCr and
      uP/Cr were comparable between the two groups up to 12 months except for sCr at
      one month (ESD group > CS group). TAC-AUC(0-12) was significantly higher in ESD
      group at one month but was equivalent thereafter, while the prevalence of biopsy
      proven tubulotoxicity was not different. MMF dose was comparable throughout the
      period between two groups. The incidence of BPAR until 12 months was equivalent.
      Of note, 60% of BPAR cases in ESD group occurred within one month. Prevalence of
      opportunistic infection or PTDM was equivalent. Graft survival was 100% in both
      groups. The following histopathologic scores up to 12 months were also
      equivalent: t, i, g, v, ci, ct, cg, cv, mm, ah, and ptc. CONCLUSIONS: Favorable
      short-term outcomes were achieved both clinically and histologically using our
      early steroid discontinuation protocol compared with the conventional protocol
      with chronic steroid treatment.

PMID- 19594590
TI  - Efficacy of tonsillectomy for patients with recurrence of IgA nephropathy after
      kidney transplantation.
AB  - From January 2007, we started to perform the tonsillectomy for every patient with
      recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September
      2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They
      had also progressive hematuria or proteinuria from on the average 14.3 months
      after transplantation. Then their specimens diagnosed as recurrent IgAN were
      collected and they underwent tonsillectomies on the average 52.3 months after
      transplantation. Abnormal urinary findings of all patients favorably improved
      after tonsillectomy. All cases but one had mild renal injury, where the severity
      of glomerular lesions, glomerular hypercellularity, segmental lesions, and
      sclerosis was mild, and no deteriorated serum creatinine (SCr) before their
      tonsillectomies. Even the case with exacerbated SCr and severe renal injury,
      where the severity of glomerular lesions was severe, had her urinary findings
      ameliorated promptly after tonsillectomy likely as others. At present, they have
      almost no symptoms after tonsillectomy and no remarkable change of SCr level
      compared with before and after tonsillectomy and maintain ameliorated urinary
      findings continuously. Tonsillectomy had possibility to be a favorable treatment
      of hematuria or proteinuria in recurrent IgAN recipients.

PMID- 19594591
TI  - A case of accelerated acute rejection after ABO-compatible living unrelated
      kidney transplantation.
AB  - A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy
      and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis
      underwent kidney transplantation from a living unrelated spousal donor. The blood
      type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6
      locus mismatch. She had become pregnant twice by her donor and had never received
      blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry
      cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She
      initially underwent one week of immunosuppression with mycophenolate mofetil
      (MMF) and double filtration plasmapheresis (DFPP) immediately before
      transplantation to reduce the risk of antibody-mediated rejection. Induction
      therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and
      basiliximab. The allograft function was excellent immediately after the
      operation. However, the urine output and platelet count declined rapidly on post
      operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase
      levels rose gradually. Subsequently, we could not detect the diastolic arterial
      flow on Doppler sonography. We diagnosed accelerated acute rejection and treated
      her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The
      first episode biopsy on POD 7 revealed acute vascular rejection and acute
      antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased
      beginning on POD 13, while the sCr level decreased gradually and reached 0.9
      mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor
      specific antibody (DSA). This case suggested that, for successful kidney
      transplantation in highly sensitized recipients, such as husband-to-wife spousal
      kidney transplantation with a history of pregnancy, we should keep the risk of
      AMR in mind, even if the sensitive antibody detection tests are negative.

PMID- 19594592
TI  - A case of acute rejection with adenovirus infection after ABO-incompatible kidney
      transplantation.
AB  - We report clinical and histopathologic findings of a case of acute rejection with
      adenovirus infection after kidney transplantation. A 63-yr-old woman with end
      stage renal disease caused by lupus nephritis received an ABO-incompatible living
      kidney transplantation from her husband. On the 7th post-operative day (POD), she
      had fever, hematuria, and bladder irritation. Although she was treated with an
      antibiotic, the symptoms were not improved. We diagnosed adenovirus infection as
      positive with the urine shell vial method and blood PCR analysis.
      Cyclophosphamide was interrupted and immunoglobulin therapy was performed.
      However, urine output decreased and serum creatinine levels increased. An episode
      biopsy was performed on POD 20. We diagnosed acute antibody-mediated rejection.
      She was treated with plasma exchange for acute rejection and antiviral drug
      (rivabirin) for active adenovirus infection. However, the renal graft dysfunction
      was deemed irreversible and the renal graft was removed on POD 34. The
      graftectomy specimen showed acute rejection and acute tubular necrosis with
      adenovirus infection.

PMID- 19594593
TI  - Successful rescue of late-onset acute T-cell mediated rejection with anti-CD25
      antibody: a case report.
AB  - Japan A 56-yr-old Japanese male with a history of diabetic nephropathy underwent
      a HLA 5/6 mismatch and ABO-compatible living-related kidney transplantation
      (donor: his 49-yr-old wife). A pre-transplant standard NIH complement-dependent
      cytotoxicity cross-match (Xm) test, a flow-cytometric T-cell Xm, and a FlowPRA
      test were totally negative. Inductionimmunosuppressive protocol consisted of
      tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab (BAS). The
      patient's post-operative course was almost uneventful, and the graft was
      functioning well (sCr 1.1 mg/dL). He developed general fatigue, and his sCr was
      elevated to 2.2 mg/dL 792 d after transplant. A graft biopsy showed acute T-cell
      mediated rejection Banff grade IB (i3, t3, g0, v0, ptc0, C4d staining negative).
      The conventional anti-rejection therapy could not improve his graft function;
      therefore, we added BAS to eliminate activated graft-infiltrating T-cells. He
      responded to the rescue therapy, and the improvement in graft function was
      confirmed by a subsequent graft biopsy. He enjoyed his health without any
      opportunistic infections.

PMID- 19594594
TI  - Subclinical peritubular capillaritis in serial graft biopsies in cadaveric kidney
      transplant recipient with pre-transplant anti-HLA antibodies.
AB  - National Fukuoka-Higashi Medical Center, Koga, Japan A 63-yr-old Japanese woman
      on 18-yr hemodialysis (HD) program underwent cadaveric kidney transplantation
      from non-heart beating donor. Pre-transplant lymphocytotoxicity test was
      negative, but flow cytometric cross-match and flow-cytometric panel reactive
      antibody (PRA) screening tests were positive. Flow-PRA single-antigen test
      revealed several anti-HLA antibodies including donor-specific antibody (DSA). She
      was treated with plasma exchange (PEX) and rituximab to prevent antibody-mediated
      rejection (AMR). Urinary output increased from post-operative day (POD) 5 and HD
      was discontinued from POD8. Graft biopsy performed on POD11 showed severe
      peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils
      (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was
      negative, the case was diagnosed as subclinical AMR based on the presence of pre
      transplant DSA and PTCitis with predominant PMNs. The patient was treated with
      additional PEX and rituximab, which increased urinary output and reduced serum
      creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe
      PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was
      negative again. The patient was discharged from the hospital on POD40. During the
      seven months follow-up at the outpatient clinic, the sCr level has shown a slight
      increase. In this case, the patient had DSA, which can be detected only by flow
      PRA. In both graft biopsies, C4d on PTC was negative despite the presence of
      severe PTCitis, and thus the diagnosis of AMR could not be established. However,
      the significance of subclinical PTCitis is reported perhaps as an early marker
      for chronic AMR and to emphasize the importance of close follow-up.

PMID- 19594595
TI  - Clinicopathological analysis of transplant glomerulopathy cases.
AB  - INTRODUCTION: Transplant glomerulopathy (TG) is involved in the criteria of
      chronic active antibody-mediated rejection (c-AMR) in Banff 07 classification. In
      this report, we discuss the clinico-pathological analysis of TG cases after renal
      transplantation, and analysis of whether all TG cases are applied to c-AMR.
      PATIENTS: Transplant glomerulopathy, defined by double contours of glomerular
      basement membranes, was diagnosed in 13 patients from 13 renal transplant
      patients followed-up in our institute between January 2007 and April 2008. We
      retrospectively reviewed these 13 patients. RESULTS: Among 13 cases of TG, three
      cases were mild (cg1 in Banff classification), four were moderate (cg2), and six
      were severe (cg3). Transplant glomerulitis and interstitial inflammation were
      present in all 13 biopsies, and peritubular capillaritis was present in 12 of 13
      biopsies, interstitial fibrosis/tubular atrophy in 13, and the thickening of the
      peritubular capillary (PTC) basement membrane in 11. PTC C4d deposition was
      presented in six cases, three out of six cases had diffuse C4d deposits in PTC,
      and the remainder had focal deposits. By assaying with plastic beads coated with
      human leukocyte antigen (HLA) in 12 cases, the circulating anti-HLA alloantibody
      was detected in all 12 patients of which only 3 of 12 were donor-specific
      antibodies (DSA). In our cases, there was no patient who fully met criteria for c
      AMR in Banff classification, which included TG, C4d deposition in PTC, and
      existence of DSA, but seven patients were diagnosed suspicious for c-AMR. Seven
      cases (54%) had proteinuria at the time of the biopsies and the severity of
      proteinuria was associated with the severity of TG. Deterioration of renal
      allografts' function after biopsies was seen in seven (54%), and two of them lost
      their graft. CONCLUSIONS: We suggest that histopathological changes of TG
      accompanied by transplant glomerulitis, peritubular capillaritis, the thickening
      of the peritubular capillaries basement membrane, and circulating anti-HLA
      antibodies may indicate c-AMR, even if C4d deposition in PTC is negative. The
      severity of TG may be associated with proteinuria, reduced graft function, and
      reduced graft survival.

PMID- 19594596
TI  - Clinical remission and pathological progression after tonsillectomy in a renal
      transplant patient with recurrent IgA nephropathy.
AB  - We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN)
      before and after tonsillectomy. A 36-year-old man started on hemodialysis support
      in 1996 due to biopsy-proven IgAN, living related renal transplantation was then
      performed in 1997. Six years after transplantation, the patient presented with
      microhematuria and proteinuria. Graft biopsy for these urinary abnormalities
      showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003,
      proteinuria remitted 6 months after the tonsillectomy and microhematuria
      disappeared three years later. Protocol graft biopsy was subsequently performed
      twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing
      the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy
      biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of
      the mesangial matrix and proliferation of mesangial interposition in 2008. In
      addition, global sclerosis of glomeruli increased over time, the area of
      tubulointerstitial damage has extended as well. While the tonsillectomy led to
      clinical remission of recurrent IgAN, the chronicity progressed on these protocol
      biopsies. This is the first report of the efficacy and the limitations of
      tonsillectomy in a case of recurrent IgAN in a transplant patient.

PMID- 19594597
TI  - Two cases of ANCA-associated vasculitis in post-transplant kidney: relapse and de
      novo.
AB  - Two cases of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis
      (ANCA-V) occurred in the transplanted kidney were reported. Case 1 was a 57 yr
      old female whose original disease was MPO-ANCA-V. A relapse of necrotizing
      crescentic glomerulonephritis occurred one year after transplantation with
      positive serum reaction for MPO-ANCA. In spite of several immunosuppressive
      treatments, the disease progressed and she returned to hemodialysis treatment
      three yr and seven months after transplantation. Case 2 was a 34 yr-old female
      whose original disease was IgA nephropathy. She had a stable clinical condition
      during 13 yr after transplantation; however, de novo onset of necrotizing
      crescentic glomerulonephritis occurred at 14 yr 10 months after transplantation
      with positive serum reaction for MPO-ANCA. She returned to hemodialysis treatment
      five yr after the onset of ANCA-V. Urinary abnormities such as microhematuria and
      proteinuria were useful diagnostic findings but the titers of serum MPO-ANCA were
      relatively low in both patients. Concerning the treatment, steroid pulse therapy
      was effective in some extents but the disease progressed to graft failure in both
      cases. ANCA-V is a severe glomerulonephritis which can occur in kidney allograft
      in the manner of relapse and de novo. Detection of urinary abnormalities and
      positive serum ANCA combined with histological confirmation of necrotizing
      crescentic glomerulonephritis and/or vasculitis is required for early diagnosis
      and effective treatment of ANCA-V in renal transplant patients.

PMID- 19594598
TI  - A long-term prevention of diabetic nephropathy in a patient with type 1 diabetes
      after simultaneous pancreas and kidney transplantation.
AB  - We report a case of type 1 diabetes mellitus who was successfully treated with
      simultaneous pancreas and kidney (SPK) transplantation and both grafts survived
      for 16 yr. A 30-yr-old woman underwent SPK transplantation from a non-heart
      beating donor in January 1992. She was treated with combined immunosuppressive
      therapy consisting of cyclosporine, azathioprine, methylprednisolone, and anti
      lymphocyte globulin. Allograft kidney biopsy was performed 10 yr after
      transplantation to determine the cause of proteinuria, which revealed no
      recurrence of diabetic nephropathy, suggesting that long-term normalization of
      glycemic control achieved by successful pancreas transplantation can prevent
      recurrence of diabetic nephropathy in the kidney allograft.

PMID- 19594599
TI  - Histopathologic evaluation of living kidney donor candidates by pre-operative
      kidney biopsy.
AB  - A lack of deceased kidney donors in Japan has led to dependence on living donors
      in as many as 80% of cases. At the same time, indications for living-donor kidney
      donation have been expanding in terms of donor medical status as well as HLA
      matching and ABO compatibility, thus emphasizing the donor shortage. To
      facilitate final medical decision-making for living kidney donation, we attempted
      kidney biopsy in six donor candidates who had problems such as mild diabetes and
      slight proteinuria. The biopsy specimens showed various degrees of tissue injury
      ranging from partial glomerular sclerosis to arteriole hyalinization. On the
      basis of the biopsy findings, kidney donation was subsequently performed in three
      of the six cases with full informed consent, and not done in the remaining three
      cases. Longer-term studies will be needed to clarify the outcome in both the
      donors and recipients in these cases.

PMID- 19594600
TI  - A case of living-related renal transplant from the donor with membranous
      nephropathy.
AB  - INTRODUCTION: When a patient who had renal replacement therapy becomes older, an
      elder donor candidate may be considered as a potential donor for living-related
      transplantation. Elder donor candidate might have pre-existing disease including
      mild renal dysfunction, such as proteinuria. Marginally appropriate donors might
      be considered for renal graft because of the shortage of donors. A successful
      outcome after kidney transplantation from a living-related donor diagnosed as
      membranous nephropathy is reported. CASE REPORT: A 38-yr-old male had been on
      continuous ambulatory peritoneal dialysis (CAPD) since the age of 37. His 63-yr
      old father had mild proteinuria, and had been diagnosed with membranous
      nephropathy by needle biopsy at the age of 60. However, renal function of the
      father was found to be stable for three yr in a preoperative examination for
      donor; the father had normal renal function except for mild proteinuria. After
      adequate informed consent, we transplanted a kidney from the father, diagnosed
      with membranous nephropathy, to his son with a cyclosporine A-based
      immunosuppression regimen. In both the recipient and the donor, postoperative
      course was stable without complication such as rejection or infection. At 57
      months after transplantation, the serum creatine level was 1.7 mg/dL in the
      recipient and 1.2 mg/dL in the donor. At 39 months after transplantation,
      allograft needle biopsy showed mild spike formation with partial thickening of
      the glomerular basement membrane (GBM). Decreases in electron-dense deposits and
      electron-lucent washout lesions with thickening of the GBM were observed using
      electron microscopy. This was diagnosed as Stage IV membranous nephropathy,
      showing clearance of the immune complexes and histological repair of the GBM.
      CONCLUSION: Donation of the kidney did not affect the residual renal function of
      the father with membranous nephropathy. Pre-existing membranous nephropathy
      itself might show remission after transplantation in the recipient. However, long
      term careful observation for both the donor and recipient is required.

PMID- 19594601
TI  - Robotic colorectal surgery: hype or new hope? A systematic review of robotics in
      colorectal surgery.
AB  - AIM: Robotic colorectal surgery is an emerging field and may offer a solution to
      some of the difficulties inherent to conventional laparoscopic surgery. The aim
      of this review is to provide a comprehensive and critical analysis of the
      available literature on the use of robotic technology in colorectal surgery.
      METHOD: Studies reporting outcomes of robotic colorectal surgery were identified
      by systematic searches of electronic databases. Outcomes examined included
      operating time, length of stay, blood loss, complications, cost, oncological
      outcome, and conversion rates. RESULTS: Seventeen Studies (nine case series,
      seven comparative studies, one randomized controlled trial) describing 288
      procedures were identified and reviewed. Study heterogeneity precluded a meta
      analysis of the data. Robotic procedures tend to take longer and cost more, but
      may reduce the length of stay, blood loss, and conversion rates. Complication
      profiles and short-term oncological outcomes are similar to laparoscopic surgery.
      CONCLUSION: Robotic colorectal surgery is a promising field and may provide a
      powerful additional tool for optimal management of more challenging pathology,
      including rectal cancer. Further studies are required to better define its role.

PMID- 19594602
TI  - Competency in laparoscopic colorectal surgery is achievable with appropriate
      training but takes time: a comparison of 300 elective resections with
      anastomosis.
AB  - AIM: The aim of this retrospective cohort study was to compare outcomes in
      patients who underwent elective laparoscopic colorectal resection with
      anastomosis performed by a single surgeon or his training fellow. METHOD: A
      prospective electronic database of all laparoscopic procedures between January
      2005 and September 2008 was used. Two groups were compared; those patients
      operated upon by the Consultant trainer (C) and those by seven supervised Fellows
      (F). Fellows were either post CCT or in their last year of training. Three
      hundred consecutive patients undergoing laparoscopic colorectal resection with
      anastomosis were examined, 150 in each group. Groups were matched for indication,
      age, American Society of Anesthesiology (ASA) grade, cancer T stage and resection
      performed. Preoperative work-up, operative surgery and anaesthesia were identical
      between groups. RESULTS: No significant difference was demonstrated in age, mean
      67 (26-91) or ASA grade. Indications for surgery were; cancer (C) 120, (F) 126,
      diverticular disease (C) 22, (F) 20, Crohn's disease (C) 8, (F) 7. Fellow's mean
      operative time was significantly longer at 123 min (95%CI 117-134) compared to
      the consultant trainer -105 min. (95%CI 98-111): P < 0.01). No significant
      differences in the complication or conversion rates were demonstrated. Length of
      stay and the 30-day readmission rates were similar. CONCLUSION: In this
      retrospective cohort study we have demonstrate that when matched patients are
      compared, supervised trainee operating time is significantly longer than that of
      the consultant trainer but without any significant increase in length of stay,
      complication or readmission rates. Training to a level of competency takes time
      but not at the expense of patient care.

PMID- 19594603
TI  - Quality of life and patient satisfaction with enhanced recovery protocols.
AB  - AIM:  The aim of this study was to systematically review the literature on the
      influence of enhanced recovery after surgery (ERAS) protocols and health related
      quality of life (HQoL) and patient satisfaction. METHOD: A systematic review of
      the literature from January 1990 to February 2009 was undertaken. Studies were
      included if they compared HQoL and/or patient satisfaction after ERAS and
      conventional surgery (CS). Jadad score was used to evaluate the studies. Results
      were divided into immediate (first week), early (second to third week) and late
      (more than 30 days after surgery) post-operative phases. A meta-analysis was not
      possible due to the heterogeneity of the studies. RESULTS: Ten publications were
      included in the final analysis. In the first week after surgery, two non
      randomised trials found reduced fatigue and another 2 non-randomised studies
      found reduced pain with ERAS. One randomised study found increased emotional
      distress on SF36 in ERAS patients. At two to three weeks after surgery, none of
      the multidimensional HQoL measures showed any differences. Increased fatigue was
      reported with CS in 2 studies. Limitations in activities of daily living were
      more marked after CS in one study. Beyond 30 days after surgery, none of the HQoL
      measures showed any differences. Only one non-randomised study compared patient
      satisfaction after ERAS and CS and no difference was found. CONCLUSION: There is
      no evidence that ERAS adversely affect HQoL or patient satisfaction. Certain
      aspects of HQoL such as pain and fatigue may improve with ERAS. Further research
      is required, especially in the early post-operative period.

PMID- 19594604
TI  - Panel of colorectal consultants to act as experts when needed for disciplinary
      tribunals, etc: a new system.

PMID- 19594605
TI  - Rectovaginal fistula: an unusual presentation.

PMID- 19594607
TI  - Multiprofessional collaboration in children's cancer care: believed to be a good
      thing but how do we know when it works well?

PMID- 19594606
TI  - Symptomatic anastomotic leakage diagnosed after hospital discharge following low
      anterior resection for rectal cancer.
AB  - OBJECTIVE: The aim of this study was to investigate patients with symptomatic
      anastomotic leakage diagnosed after hospital discharge. METHOD: Patients (n =
      234) undergoing low anterior resection of the rectum for cancer who were included
      in a prospective multicentre trial (NCT 00636948) and who developed symptomatic
      anastomotic leakage diagnosed after hospital discharge (late leakage, LL; n = 18)
      were identified. Patient characteristics, operative details, recovery on
      postoperative day 5, length of hospital stay, and how the leakage was diagnosed
      were recorded. A comparison with those who did not develop symptomatic leakage
      (no leakage, NL; n = 189) was made. The minimum follow up was 24 months. RESULTS:
      In the LL patients the median age was 69 years, 61% were female patients, and 6%
      had stage IV cancer disease. On postoperative day 5, the LL group had a
      postoperative course similar to the NL group regarding temperature, oral intake
      and bowel function. The proportion of patients on antibiotic treatment on
      postoperative day 5, regardless of indication, was 28% in the LL compared with 4%
      in the NL group (P < 0.001). The median initial hospital stay was 10 days for
      both groups. When readmission for any reason was added, the hospital stay rose to
      a median of 21.5 and 13 days in the LL and the NL groups respectively (P <
      0.001). CONCLUSION: Symptomatic anastomotic leakage diagnosed after hospital
      discharge following low anterior resection of the rectum for cancer is not
      uncommon and has an immediate clinical postoperative course which may appear
      uneventful.

PMID- 19594608
TI  - Breaking bad news - whose responsibility is it?
AB  - This module considers different aspects of communicating a cancer diagnosis to
      the patient. Using a UK study, it looks at who breaks bad news in cancer care,
      frameworks for breaking bad news and the role of nurses.

PMID- 19594609
TI  - Male and female experiences of having fertility matters raised alongside a cancer
      diagnosis during the teenage and young adult years.
AB  - Discussion and management of potential reproductive health sequelae of adolescent
      cancer are essential and challenging components of care for the multidisciplinary
      team. Despite this, research has been limited to specific experiences (e.g. sperm
      banking) or fertility-related concerns of adult survivors. This grounded theory
      study of 38 male and female survivors of adolescent cancer aged 16-30 years drew
      on in-depth single interviews to map the range of experiences of being advised
      that treatment might affect fertility. Strong support for being told at around
      diagnosis was found regardless of gender, age, incapacity or availability of
      fertility preservation services. Age and life stage appeared less significant for
      impact than the perceived level of threat to personal and social well-being.
      Women were more likely to achieve lower levels of comprehension about the
      physiological impact, to report later distress from lack of fertility
      preservation services and to revisit more frequently those decisions made by the
      few offered fertility preservation. Men found decision making about sperm banking
      straightforward on the whole and reported satisfaction with having the choice
      regardless of outcome. Findings suggest that young people can cope with this
      information alongside diagnosis especially when professional and parental support
      is proportionate to the particular impact on them.

PMID- 19594611
TI  - School-aged children after the end of successful treatment of non-central nervous
      system cancer: longitudinal assessment of health-related quality of life, anxiety
      and coping.
AB  - The aim of the study was to investigate: (1) health-related quality of life
      (HRQoL) and anxiety in school-aged cancer survivors during the first 4 years of
      continuous remission after the end of treatment; and (2) correlations of disease
      related coping with HRQoL and anxiety. A total of 76 survivors aged 8-15 years
      completed questionnaires about HRQoL, anxiety and disease-related cognitive
      coping at one to five measurement occasions. Their HRQoL was compared with norm
      data, 2 months (n = 49) and 1 year (n = 41), 2 years (n = 41), 3 years (n = 42)
      and 4 years (n = 27) after treatment. Through longitudinal mixed models analyses
      it was investigated to what extent disease-related cognitive coping was
      associated with HRQoL and anxiety over time, independent of the impact of
      demographic and medical variables. Survivors reported worse Motor Functioning
      (HRQoL) 2 months after the end of treatment, but from 1 year after treatment they
      did no longer differ from the norm population. Lower levels of anxiety were
      associated with male gender, being more optimistic about the further course of
      the disease (predictive control) and less searching for information about the
      disease (interpretative control). Stronger reliance on the physician (vicarious
      control) was associated with better mental HRQoL. As a group, survivors regained
      good HRQoL from 1 year after treatment. Monitoring and screening survivors are
      necessary to be able to trace the survivors at risk of worse HRQoL.

PMID- 19594610
TI  - Seeking consent to tissue banking: a survey of health professionals in childhood
      cancer.
AB  - To identify the views of health professionals working in childhood cancer on
      seeking consent to tissue banking from potential donors. Self-completion
      questionnaires sent to 553 UK paediatric oncology health professionals. The
      response rate was 60%. Respondents (100%) were in favour of using tissue samples
      from children with cancer for research. A substantial minority (30%) had concerns
      about the impact of the law on their professional role in relation to tissue
      banking. Almost all (90%) reported that both the parent(s) and the child, if
      able, should be asked for consent, though the UK Human Tissue Act provides that a
      competent child's consent is sufficient. Most (94%) supported 'generic' rather
      than 'specific' consent. Barriers to obtaining consent included: (1) timing of
      the approach to families; (2) availability of suitable staff; (3) sensitivity of
      the issues; (4) difficulties of managing the process; and (5) problems of
      maintaining a paper trail. Many would welcome training on seeking consent.
      Personal knowledge and relationships with families are often seen as important in
      guiding the proper approach to consent rather than formalized rules. There is
      widespread support among health professionals for tissue banking in childhood
      cancer. In sensitive situations, disciplined exercise of professional discretion
      might better deliver on aspirations for regulation than rigid procedures.

PMID- 19594612
TI  - Feasibility of a school reintegration programme for children with acute
      lymphoblastic leukaemia.
AB  - Despite children with acute lymphoblastic leukaemia missing a significant amount
      of school, little empirical literature guides the optimal content, setting and
      timing of a school reintegration programme. We examined the feasibility of a 4
      month school reintegration intervention by: (1) developing collaboration with a
      community-based advocacy organisation; (2) developing intervention modules and
      observable end points; and (3) determining how the study achieved recruitment
      expectations. Eight families with children aged 6-12 years diagnosed with acute
      lymphoblastic leukaemia and parents were enrolled in the study. An experienced
      advocate implemented a series of eight modules over a 4-month period (twice per
      month) with the families. Participants completed pre-post measures. Successful
      collaboration with the advocacy organisation and the development of an
      intervention module series were achieved. Recruitment aims proved more difficult:
      enrolment was extended when recruitment for the original 1- to 6-month post
      diagnosis window proved difficult. The advocate was able to complete between
      three and seven of the modules (mean = 5.2, standard deviation = 1.5). Families
      preferred clinic-based intervention. Challenges faced and lessons learned
      include: (1) advocacy organisations may be useful resources for school
      reintegration interventions; (2) school reintegration interventions must be
      flexibly applied; and (3) measurement end points constructed to gauge programme
      effectiveness.

PMID- 19594613
TI  - Re: BAKER P.J. & HOEL D.G. (2007) European Journal of Cancer Care16, 355-363.
      Meta-analysis of standardized incidence and mortality rates of childhood
      leukaemia in proximity to nuclear facilities.

PMID- 19594615
TI  - Acquired Glanzmann's thrombasthenia associated with Hairy cell leukaemia.

PMID- 19594616
TI  - Interphase FISH on TEL/AML1 positive acute lymphoblastic leukemia relapses-
      analysis of clinical relevance of additional TEL and AML1 copy number changes.
AB  - OBJECTIVES: TEL/AML1 (ETV6/RUNX1) fusion resulting from the translocation
      t(12;21)(p13;q22) constitutes the most common chimeric fusion gene in initial
      childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) (19-27%) and
      has been associated with good prognosis. Three secondary aberrations in TEL/AML1
      positive ALL have been suspected to negatively influence outcome: deletion of the
      second TEL allele (T), gain of the second AML1 allele (A) and duplication of the
      derivative chromosome 21 (der(21), TA). Many studies have explored such
      aberrations in initial disease, while only few reports have investigated them in
      relapses. METHODS: In this study, bone marrow samples from 38 children with
      relapsed TEL/AML1 RT-PCR positive and negative BCP-ALL were analyzed for these
      mutations by interphase fluorescence in situ hybridization and results were
      compared with published data. RESULTS: In children with TEL/AML1 positive ALL
      relapse, additional (a) TEL loss, (b) combined AML1 and der(21) gain, (c)
      combined TEL loss and AML1 gain as well as (d) the occurrence of a subpopulation
      with the signal pattern 1T/3A/1TA appear to be related to higher peripheral blast
      counts (PBCs) at relapse diagnosis (a and d) or a tendency towards the occurrence
      of a subsequent relapse (b and c) (P-values <0.05). CONCLUSIONS: Our data
      together with published results on TEL/AML1 positive ALL suggest that frequencies
      of additional TEL and AML1 mutations are, with the exception of loss of
      untranslocated TEL, higher in first relapses than in initial disease. They also
      show that it is important to consider combined mutations in the analysis of this
      leukemia entity.

PMID- 19594618
TI  - Analysis of telomere length in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a well defined lymphoid neoplasm genetically
      characterized by the t(11;14)(q13;q32). Telomeres play an essential role in
      preserving chromosomal integrity and genomic stability; their shortening can lead
      to telomere dysfunction and chromosomal instability, a critical factor in cancer
      development. In this study, telomere length (TL) measured by terminal restriction
      fragments (TRF) assay in DNA samples of tumor cells from 20 patients with MCL was
      evaluated. Results were correlated with clinical, morphologic and cytogenetic
      characteristics. In all cases, the presence of the CCND1/IGH@ rearrangement was
      confirmed by fluorescence in situ hybridization and/or PCR analysis. TL in total
      MCL patients revealed a mean TRF value (4.51 +/- 0.79 kb) significantly shorter
      than those observed in controls (7.49 +/- 1.94 kb) (P < 0.001); 30% of patients
      had TL shorter than 4.0 kb. TRF length was not associated with patients age (P =
      0.07; r = 0.17) nor with sex (females: 4.33 +/- 0.51 kb and males: 4.57 +/- 0.85
      kb; P = 0.63). No significant differences were found between patients studied at
      diagnosis (13) (4.44 +/- 0.81 kb) respect to those analyzed at relapse (7) (4.63
      +/- 0.82 kb) (P = 0.53). In addition, we compared patients with (4.84 +/- 1.09
      kb) and without (4.40 +/- 0.68 kb) complex karyotypes (P = 0.45) and cases with
      typical morphology (4.48 +/- 0.79 kb) vs. blastoid variant (4.63 +/- 1.04 kb) (P
      = 0.83), and no significant differences between them were found. Although the
      number of cases of our series is not large, our results showed that TL reduction
      in MCL is independent of the clinical characteristics, morphology and karyotype.

PMID- 19594617
TI  - Heart rate variability in beta-thalassemia patients.
AB  - BACKGROUND: Cardiac failure remains the major cause of death in beta-thalassemia
      major (TM). Reduced heart rate variability (HRV) is associated with a higher risk
      of arrhythmias after myocardial infarction and heart failure. We evaluated HRV in
      TM patients and its relationship with hemodynamics and echocardiographic
      parameters during a 6-month follow-up. METHODS: Thirty-four TM patients (19 +/-
      10 yr) and 20 healthy subjects (17 +/- 6 yr) were evaluated. Hematologic,
      biochemical, echocardiographic and HRV parameters were determined at entry and at
      6-month follow-up. Time and frequency domain HRV parameters were analyzed from 24
      h recorded electrocardiograms. All TM patients received blood transfusion and
      chelation therapy. RESULTS: Both time and frequency domain HRV parameters were
      markedly reduced in TM patients, compared to the control. The significantly
      improved HRV was seen in correlation with higher hemoglobin (Hb) level when
      compared within TM group at different time point. No correlation was seen between
      HRV and serum ferritin, reactive oxygen species (ROS) and non-transferrin bound
      iron (NTBI). CONCLUSION: HRV is depressed in TM patients. HRV was significantly
      correlated with Hb level, suggesting that anemia greatly influences the cardiac
      autonomic balance.

PMID- 19594619
TI  - FGFR3 is expressed and is important for survival in INA-6, a human myeloma cell
      line without a t(4;14).
AB  - OBJECTIVES: Fibroblast growth factor receptor 3 (FGFR3) is a proto-oncogene that
      is often dysregulated together with multiple myeloma SET-domain (MMSET) by the
      immunoglobulin heavy chain (IGH) gene in t(4;14)(pos) multiple myeloma (MM)
      cells, and which is usually not expressed in MM cells without this translocation.
      Whether FGFR3 may play a role in MM cells without t(4;14) and the IGH-MMSET
      fusion protein is unclear and is the focus of this report. METHODS: FGFR3
      expression was explored in cell lines with and without t(4;14) by fluorescence in
      situ hybridization (FISH), RT-PCR and Western Blot. FGFR3 inhibitors SU5402 and
      PD173074 were used to explore the role of FGFR3 in these cells. RESULTS: We
      discovered an amplification of the FGFR3 locus in INA-6, a human MM cell line. We
      also demonstrated expression of FGFR3 mRNA and protein in the cells, probably
      caused by the extra copy of the gene. INA-6 cells did not have t(4;14) and
      neither was there any involvement of the other IG loci in translocations with the
      FGFR3 gene. The FGFR3 inhibitors decreased the proliferation of INA-6.
      CONCLUSION: The decreased viability and proliferation in INA-6, following
      inhibition with FGFR3 inhibitors, indicates that FGFR3 may play a role also in
      cells without t(4;14) - and hence without high expression of MMSET, the
      ubiquitous oncoprotein in MM cells with t(4;14). This gives further credibility
      to the notion that FGFR3 expression is not just an epiphenomenon in t(4;14) MM,
      but an important part of the malignant phenotype.

PMID- 19594620
TI  - Chemical and electroporated transformation of Edwardsiella ictaluri using three
      different plasmids.
AB  - Transfer of DNA by conjugation has been the method generally used for genetic
      manipulation of Edwardsiella ictaluri because, previously, attempts to transform
      E. ictaluri by the uptake of naked DNA have apparently failed. We report here the
      successful transformation of seven strains of E. ictaluri using electroporation
      and two different chemical procedures [conventional calcium chloride (CaCl(2))
      and 'one-step' (polyethylene glycol, dimethyl sulfoxide and MgSO(4)) protocols].
      Seven strains of E. ictaluri were transformed using three different plasmids
      [pZsGreen, pUC18 and pET-30a(+)]. The highest transformation efficiency was
      achieved by electroporation (5.5+/-0.2 x 10(4) transformants ng(-1) plasmid DNA)
      than with the CaCl(2) (8.1+/-6.1 x 10(-1) transformants ng(-1) plasmid) and the
      'one-step transformation' protocol (2.5+/-2.7 transformants ng(-1) plasmid). An
      efficient transformation by electroporation required only 0.2 ng of plasmid
      compared with 200 ng required for the CaCl(2) and one-step protocols. The
      plasmids were stably maintained in E. ictaluri grown in the presence of
      antibiotic for 12 or more passages. The results of this study show that
      transformation of E. ictaluri by electroporation can be routinely used for the
      molecular genetic manipulation of this organism, and is a quicker and easier
      method than transformation performed by conjugation.

PMID- 19594621
TI  - Identification and distribution of accessory genome DNA sequences from an
      invasive African isolate of Salmonella Heidelberg.
AB  - Nontyphoidal salmonellae (NTS) are a leading cause of invasive disease in young
      children in sub-Saharan Africa. We used suppression subtractive hybridization
      (SSH) to identify 41 sequences within the accessory genome of an invasive strain
      of Salmonella Heidelberg from Malawi. PCR assays and database searches, used to
      determine the distribution of 14 SSH sequences among a panel of African and UK
      NTS isolates and published genomes, indicated that two were specific for S.
      Heidelberg. However, we found no evidence for major differences in the accessory
      genome content between African invasive and gastrointestinal isolates of S.
      Heidelberg. Six of the SSH sequences were within fimbrial operons. The tcf
      operon, associated with the host specificity of Salmonella Typhi, and the stk
      operon, reported previously in Salmonella Paratyphi, were both present in either
      all (tcf) or most (stk) isolates of S. Heidelberg, but had restricted
      distributions among the other serovars tested. Reverse transcription PCR analysis
      of seven SSH sequences indicated variable expression of the stk operon among
      isolates of S. Heidelberg. Three of the seven targeted genes were not expressed
      in a UK veterinary isolate of S. Heidelberg, suggesting that although genome
      content per se may not explain the different pathogenicity of the invasive
      isolates, it is possible that variations in gene expression may play a role.

PMID- 19594622
TI  - Gene cloning and characterization of a deaminase from the 4-amino-3
      hydroxybenzoate-assimilating Bordetella sp. strain 10d.
AB  - The 4-amino-3-hydroxybenzoate-assimilating Bordetella sp. strain 10d produces a
      deaminase that catalyzes the deamination of 2-amino-5-carboxymuconic 6
      semialdehyde. A gene encoding the deaminase, ahdB, was cloned and expressed in
      Escherichia coli; ahdB is located downstream from the previously reported genes
      encoding 4-amino-3-hydroxybenzoate 2,3-dioxygenase (ahdA) and a LysR-type
      regulator. The deduced amino acid sequence of ahdB shows 30-33% identity to those
      of previously reported 2-aminomuconate deaminases. We identified a region
      (RAGDFLXVSG) conserved in AhdB and three other deaminases. The recombinant enzyme
      AhdB was purified to homogeneity. After a coupled enzyme assay with purified
      AhdA, AhdB, and the substrate 4-amino-3-hydroxybenzoate, the final product,
      formed by the action of AhdA, AhdB, and by nonenzymatic decarboxylation, was
      identified by HPLC, MS, and (1)H-nuclear magnetic resonance analyses as 2
      hydroxymuconic 6-semialdehyde.

PMID- 19594623
TI  - The streptococcal inhibitor of complement (SIC) protects Streptococcus pyogenes 
      from bacteriocin-like inhibitory substance (BLIS) from Streptococcus salivarius.
AB  - Streptococcus salivarius inhibits the growth of Streptococcus pyogenes in vitro.
      Streptococcus pyogenes has various virulence factors, including the streptococcus
      inhibitor of complement (SIC). Although SIC inhibits the activity of the peptides
      LL-37 and NAP1, the relationship between SIC and the bacteriocin-like inhibitory
      substance (BLIS) has not been elucidated. Here, we evaluated whether S.
      salivarius BLIS affects S. pyogenes SIC. We created three deltasic mutant strains
      from three S. pyogenes strains and performed deferred antagonism assays. The test
      strains were BLIS-positive S. salivarius JCM5707 and BLIS-negative S. salivarius
      NCU12. Deferred antagonism assays with JCM5707 showed that the inhibitory zones
      in the three deltasic mutant strains were wider than those in the three wild-type
      strains. Streptococcus pyogenes was cultured in BLIS-containing broth and the
      change in SIC in the supernatant was assessed by two-dimensional gel
      electrophoresis (2-DE). The 2-DE analysis of S. pyogenes exoproteins with the
      JCM5707 supernatant showed reduced SIC compared with those without the JCM5707
      supernatant. Changes in sic mRNA levels affected by S. salivarius BLIS were
      evaluated by a reverse transcriptase-PCR. The sic mRNA level was affected more by
      the BLIS-positive S. salivarius than by the BLIS-negative strain. Our result
      indicates that SIC plays a role in the inhibition of S. salivarius BLIS.

PMID- 19594624
TI  - Two different mechanisms of ampicillin resistance operating in strains of Vibrio
      cholerae O1 independent of resistance genes.
AB  - Autoagglutinable strains of Vibrio cholerae O1 (seven nonfimbriate strains and
      one fimbriate strain) were transformed to obtain resistance to ampicillin. Two
      distinct mechanisms were found in these strains. One was operating in
      nonfimbriate strains by reducing OmpU protein production and the other was
      operating in a fimbriate strain (Bgd17) by newly overproducing cpxP protein. The
      twitching motility in the fimbriate Bgd17 strain disappeared depending on the
      production of cpxP protein, suggesting that fimbriation of V. cholerae O1 is
      controlled by a two-component signal transduction system.

PMID- 19594625
TI  - Glycoimmunology: ignore at your peril!

PMID- 19594626
TI  - Mannose-binding lectin and innate immunity.
AB  - Innate immunity is the earliest response to invading microbes and acts to contain
      infection in the first minutes to hours of challenge. Unlike adaptive immunity
      that relies upon clonal expansion of cells that emerge days after antigenic
      challenge, the innate immune response is immediate. Soluble mediators, including
      complement components and the mannose binding lectin (MBL) make an important
      contribution to innate immune protection and work along with epithelial barriers,
      cellular defenses such as phagocytosis, and pattern-recognition receptors that
      trigger pro-inflammatory signaling cascades. These four aspects of the innate
      immune system act in concert to protect from pathogen invasion. Our work has
      focused on understanding the protection provided by this complex defense system
      and, as discussed in this review, the particular contribution of soluble
      mediators such as MBL and phagocytic cells. Over the past two decades both human
      epidemiological data and mouse models have indicated that MBL plays a critical
      role in innate immune protection against a number of pathogens. As demonstrated
      by our recent in vitro work, we show that MBL and the innate immune signaling
      triggered by the canonical pattern-recognition receptors (PRRs), the Toll-like
      receptors (TLRs), are linked by their spatial localization to the phagosome.
      These observations demonstrated a novel role for MBL as a TLR co-receptor and
      establishes a new paradigm for the role of opsonins, which we propose to function
      not only to increase microbial uptake but also to spatially coordinate, amplify,
      and synchronize innate immune defenses mechanism. In this review we discuss both
      the attributes of MBL that make it a unique soluble pattern recognition molecule
      and also highlight its broader role in coordinating innate immune activation.

PMID- 19594627
TI  - Endogenous ligands for C-type lectin receptors: the true regulators of immune
      homeostasis.
AB  - C-type lectin receptors (CLRs) have long been known as pattern-recognition
      receptors implicated in the recognition of pathogens by the innate immune system.
      However, evidence is accumulating that many CLRs are also able to recognize
      endogenous 'self' ligands and that this recognition event often plays an
      important role in immune homeostasis. In the present review, we focus on the
      human and mouse CLRs for which endogenous ligands have been described. Special
      attention is given to the signaling events initiated upon recognition of the self
      ligand and the regulation of glycosylation as a switch modulating CLR
      recognition, and therefore, immune homeostasis.

PMID- 19594628
TI  - Beta-glucan recognition by the innate immune system.
AB  - Beta-glucans are recognized by the innate immune system. This recognition plays
      important roles in host defense and presents specific opportunities for clinical
      modulation of the host immune response. Neutrophils, macrophages, and dendritic
      cells among others express several receptors capable of recognizing beta-glucan
      in its various forms. This review explores what is currently known about beta
      glucan recognition and how this recognition stimulates immune responses. Special
      emphasis is placed on Dectin-1, as we know the most about how this key beta
      glucan receptor translates recognition into intracellular signaling, stimulates
      cellular responses, and participates in orchestrating the adaptive immune
      response.

PMID- 19594630
TI  - PSGL-1 function in immunity and steady state homeostasis.
AB  - The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in
      leukocyte trafficking has continued to emerge beyond its initial identification
      as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an
      extracellular mucin domain extended as a flexible rod, teleologically consistent
      with its primary role in tethering leukocytes to endothelial selectins. The
      rolling interaction between leukocyte and endothelium mediated by this selectin
      PSGL-1 interaction requires branched O-glycan extensions on specific PSGL-1 amino
      acid residues. In some cells, such as neutrophils, the glycosyltransferases
      involved in formation of the O-glycans are constitutively expressed, while in
      other cells, such as T cells, they are expressed only after appropriate
      activation. Thus, PSGL-1 supports leukocyte recruitment in both innate and
      adaptive arms of the immune response. A complex array of amino acids within the
      selectins engage multiple sugar residues of the branched O-glycans on PSGL-1 and
      provide the molecular interactions responsible for the velcro-like catch bonds
      that support leukocyte rolling. Such binding of PSGL-1 can also induce signaling
      events that influence cell phenotype and function. Scrutiny of PSGL-1 has
      revealed a better understanding of how it performs as a selectin ligand and
      yielded unexpected insights that extend its scope from supporting leukocyte
      rolling in inflammatory settings to homeostasis including stem cell homing to the
      thymus and mature T-cell homing to secondary lymphoid organs. PSGL-1 has been
      found to bind homeostatic chemokines CCL19 and CCL21 and to support the
      chemotactic response to these chemokines. Surprisingly, the O-glycan
      modifications of PSGL-1 that support rolling mediated by selectins in
      inflammatory conditions interfere with PSGL-1 binding to homeostatic chemokines
      and thereby limit responsiveness to the chemotactic cues used in steady state T
      cell traffic. The multi-level influence of PSGL-1 on cell traffic in both
      inflammatory and steady state settings is therefore substantially determined by
      the orchestrated addition of O-glycans. However, central as specific O
      glycosylation is to PSGL-1 function, in vivo regulation of PSGL-1 glycosylation
      in T cells remains poorly understood. It is our purpose herein to review what is
      known, and not known, of PSGL-1 glycosylation and to update understanding of PSGL
      1 functional scope.

PMID- 19594629
TI  - Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL:
      engineering a roadmap for cell migration.
AB  - During evolution of the vertebrate cardiovascular system, the vast endothelial
      surface area associated with branching vascular networks mandated the development
      of molecular processes to efficiently and specifically recruit circulating
      sentinel host defense cells and tissue repair cells at localized sites of
      inflammation/tissue injury. The forces engendered by high-velocity blood flow
      commensurately required the evolution of specialized cell surface molecules
      capable of mediating shear-resistant endothelial adhesive interactions, thus
      literally capturing relevant cells from the blood stream onto the target
      endothelial surface and permitting subsequent extravasation. The principal
      effectors of these shear-resistant binding interactions comprise a family of C
      type lectins known as 'selectins' that bind discrete sialofucosylated glycans on
      their respective ligands. This review explains the 'intelligent design' of
      requisite reagents to convert native CD44 into the sialofucosylated glycoform
      known as hematopoietic cell E-/L-selectin ligand (HCELL), the most potent E
      selectin counter-receptor expressed on human cells, and will describe how ex vivo
      glycan engineering of HCELL expression may open the 'avenues' for the efficient
      vascular delivery of cells for a variety of cell therapies.

PMID- 19594632
TI  - Galectin-3 regulates T-cell functions.
AB  - Galectin-3 is absent in resting CD4+ and CD8+ T cells but is inducible by various
      stimuli. These include viral transactivating factors, T-cell receptor (TCR)
      ligation, and calcium ionophores. In addition, galectin-3 is constitutively
      expressed in human regulatory T cells and CD4+ memory T cells. Galectin-3 exerts
      extracellular functions because of its lectin activity and recognition of cell
      surface and extracellular matrix glycans. These include cell activation,
      adhesion, induction of apoptosis, and formation of lattices with cell surface
      glycoprotein receptors. Formation of lattices can result in restriction of
      receptor mobility and cause attenuation of receptor functions. Consistent with
      the presence of galectin-3 in intracellular locations, several functions have
      been described for this protein inside T cells. These include inhibition of
      apoptosis, promotion of cell growth, and regulation of TCR signal transduction.
      Studies of cell surface glycosylation have led to convergence of glycobiology and
      galectin biology and provided new clues on how galectin-3 may participate in the
      regulation of cell surface receptor activities. The rapid expansion of the field
      of galectin research has positioned galectin-3 as a key regulator in T-cell
      functions.

PMID- 19594633
TI  - CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions.
AB  - Siglecs (sialic acid-binding immunoglobulin-like lectins) are sialic acid-binding
      proteins, which are expressed on many cell types of the immune system. B cells
      express two members of the Siglec family, CD22 (Siglec-2) and Siglec-G, both of
      which have been shown to inhibit B-cell signaling. CD22 recruits the tyrosine
      phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1) to
      immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and inhibits B-cell
      receptor (BCR)-induced Ca2+ signaling on normal B cells. CD22 interacts
      specifically with ligands carrying alpha2-6-linked sialic acids. Interaction with
      these ligands in cis regulates the association of CD22 with the BCR and thereby
      modulates the inhibitory function of CD22. Interaction of CD22 to ligands in
      trans can regulate both B-cell migration as well as the BCR signaling threshold.
      Siglec-G is a recently identified protein with an inhibitory function restricted
      to a B-cell subset, the B1 cells. Siglec-G inhibits Ca2+ signaling specifically
      in these cells. In addition, it controls the cellular expansion and antibody
      secretion of B1 cells. Thus, both Siglecs modulate BCR signaling on different B
      cell populations in a mutually exclusive fashion.

PMID- 19594635
TI  - The regulation of inflammation by galectin-3.
AB  - Galectin-3 is a beta-galactoside-binding animal lectin of approximately 30 kDa
      and is evolutionarily highly conserved. Galectin-3 is promiscuous, its
      localization within the tissue micro-environment may be extracellular,
      cytoplasmic, or nuclear, and it has a concentration-dependent ability to be
      monomeric or form oligomers. These properties impart great flexibility on
      galectin-3 as a specific regulator of many biological systems including
      inflammation. For example, in acute tissue damage galectin-3 is a key component
      in the host defense against microbes such as Streptococcus pneumoniae. However,
      if tissue injury becomes repetitive galectin-3 also appears to be intimately
      involved in the transition to chronic inflammation, facilitating the walling off
      of tissue injury with fibrogenesis and organ scarring. Therefore galectin-3 can
      be viewed as a regulatory molecule acting at various stages along the continuum
      from acute inflammation to chronic inflammation and tissue fibrogenesis. In this
      review, we examine the role of galectin-3 in inflammation, and discuss the
      manipulation of galectin-3 expression as a potentially novel therapeutic strategy
      in the treatment of a broad range of inflammatory diseases.

PMID- 19594634
TI  - Conveying glycan information into T-cell homeostatic programs: a challenging role
      for galectin-1 in inflammatory and tumor microenvironments.
AB  - The immune system has evolved sophisticated mechanisms composed of several
      checkpoints and fail-safe processes that enable it to orchestrate innate and
      adaptive immunity, while at the same time limiting aberrant or unfaithful T-cell
      function. These multiple regulatory pathways take place during the entire life
      span of T cells including T-cell development, homing, activation, and
      differentiation. Galectin-1, an endogenous glycan-binding protein widely
      expressed at sites of inflammation and tumor growth, controls a diversity of
      immune cell processes, acting either extracellularly through specific binding to
      cell surface glycan structures or intracellularly through modulation of pathways
      that remain largely unexplored. In this review, we highlight the discoveries that
      have led to our current understanding of the role of galectin-1 in distinct
      immune cell process, particularly those associated with T-cell homeostasis. Also,
      we emphasize findings emerging from the study of experimental models of
      autoimmunity, chronic inflammation, fetomaternal tolerance, and tumor growth,
      which have provided fundamental insights into the critical role of galectin-1 and
      its specific saccharide ligands in immunoregulation. Challenges for the future
      will embrace the rational manipulation of galectin-1-glycan interactions both
      towards attenuating immune responses in autoimmune diseases, graft rejection, and
      recurrent fetal loss, while at the same overcoming immune tolerance in chronic
      infections and cancer.

PMID- 19594631
TI  - Glycosylation in immune cell trafficking.
AB  - Leukocyte recruitment encompasses cell adhesion and activation steps that enable
      circulating leukocytes to roll, arrest, and firmly adhere on the endothelial
      surface before they extravasate into distinct tissue locations. This complex
      sequence of events relies on adhesive interactions between surface structures on
      leukocytes and endothelial cells and also on signals generated during the cell
      cell contacts. Cell surface glycans play a crucial role in leukocyte recruitment.
      Several glycosyltransferases such as alpha1,3 fucosyltransferases, alpha2,3
      sialyltransferases, core 2 N-acetylglucosaminlytransferases, beta1,4
      galactosyltransferases, and polypeptide N-acetylgalactosaminyltransferases have
      been implicated in the generation of functional selectin ligands that mediate
      leukocyte rolling via binding to selectins. Recent evidence also suggests a role
      of alpha2,3 sialylated carbohydrate determinants in triggering chemokine-mediated
      leukocyte arrest and influencing beta1 integrin function. The recent discovery of
      galectin- and siglec-dependent processes further emphasizes the significant role
      of glycans for the successful recruitment of leukocytes into tissues. Advancing
      the knowledge on glycan function into appropriate pathology models is likely to
      suggest interesting new therapeutic strategies in the treatment of immune- and
      inflammation-mediated diseases.

PMID- 19594636
TI  - Galectins in innate immunity: dual functions of host soluble beta-galactoside
      binding lectins as damage-associated molecular patterns (DAMPs) and as receptors
      for pathogen-associated molecular patterns (PAMPs).
AB  - The glycocalyx is a glycan layer found on the surfaces of host cells as well as
      microorganisms and enveloped virus. Its thickness may easily exceed 50 nm. The
      glycocalyx does not only serve as a physical protective barrier but also contains
      various structurally different glycans, which provide cell- or microorganism
      specific 'glycoinformation'. This information is decoded by host glycan-binding
      proteins, lectins. The roles of lectins in innate immunity are well established,
      as exemplified by collectins, dectin-1, and dendritic cell (DC)-specific
      intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). These
      mammalian lectins are synthesized in the secretory pathway and presented on the
      cell surface to bind to specific glycan 'epitopes'. As they recognize non-self
      glycans presented by microorganisms, they can be considered as receptors for
      pathogen-associated molecular patterns (PAMPs), i.e. pattern recognition
      receptors (PRRs). One notable exception is the galectin family. Galectins are
      synthesized and stored in the cytoplasm, but upon infection-initiated tissue
      damage and/or following prolonged infection, cytosolic galectins are either
      passively released by dying cells or actively secreted by inflammatory activated
      cells through a non-classical pathway, the 'leaderless' secretory pathway. Once
      exported, galectins act as PRR, as well as immunomodulators (or cytokine-like
      modulators) in the innate response to some infectious diseases. As galectins are
      dominantly found in the lesions where pathogen-initiated tissue damage signals
      appear, this lectin family is also considered as potential damage-associated
      molecular pattern (DAMP) candidates that orchestrate innate immune responses
      alongside the PAMP system.

PMID- 19594637
TI  - Carbohydrate specificity of the recognition of diverse glycolipids by natural
      killer T cells.
AB  - Most T lymphocytes recognize peptide antigens bound to or presented by molecules
      encoded in the major histocompatibility complex (MHC). The CD1 family of antigen
      presenting molecules is related to the MHC-encoded molecules, but CD1 proteins
      present lipid antigens, mostly glycolipids. Here we review T-lymphocyte
      recognition of glycolipids, with particular emphasis on the subpopulation known
      as natural killer T (NKT) cells. NKT cells influence many immune responses, they
      have a T-cell antigen receptor (TCR) that is restricted in diversity, and they
      share properties with cells of the innate immune system. NKT cells recognize
      antigens presented by CD1d with hexose sugars in alpha-linkage to lipids,
      although other, related antigens are known. The hydrophobic alkyl chains are
      buried in the CD1d groove, with the carbohydrate exposed for TCR recognition,
      together with the surface of the CD1d molecule. Therefore, understanding the
      biochemical basis for antigen recognition by NKT cells requires an understanding
      of how the trimolecular complex of CD1d, glycolipid, and the TCR is formed, which
      is in part a problem of carbohydrate recognition by the TCR. Recent
      investigations from our laboratories as well as studies from other groups have
      provided important information on the structural basis for NKT-cell specificity.

PMID- 19594638
TI  - Regulation of Notch signaling during T- and B-cell development by O-fucose
      glycans.
AB  - Notch signaling is required for the development of all T cells and marginal zone
      (MZ) B cells. Specific roles in T- and B-cell differentiation have been
      identified for different Notch receptors, the canonical Delta-like (Dll) and
      Jagged (Jag) Notch ligands, and downstream effectors of Notch signaling. Notch
      receptors and ligands are post-translationally modified by the addition of
      glycans to extracellular domain epidermal growth factor-like (EGF) repeats. The O
      fucose glycans of Notch cell-autonomously modulate Notch-ligand interactions and
      the strength of Notch signaling. These glycans are initiated by protein O
      fucosyltransferase 1 (Pofut1), and elongated by the transfer of N
      acetylglucosamine (GlcNAc) to the fucose by beta1,3GlcNAc-transferases termed
      lunatic, manic, or radical fringe. This review discusses T- and B-cell
      development from progenitors deficient in O-fucose glycans. The combined data
      show that Lfng and Mfng regulate T-cell development by enhancing the interactions
      of Notch1 in T-cell progenitors with Dll4 on thymic epithelial cells. In the
      spleen, Lfng and Mfng cooperate to modify Notch2 in MZ B progenitors, enhancing
      their interaction with Dll1 on endothelial cells and regulating MZ B-cell
      production. Removal of O-fucose affects Notch signaling in myelopoiesis and
      lymphopoiesis, and the O-fucose glycan in the Notch1 ligand-binding domain is
      required for optimal T-cell development.

PMID- 19594639
TI  - Immunological functions of hyaluronan and its receptors in the lymphatics.
AB  - The lymphatic system is best known for draining interstitial fluid from the
      tissues and returning it to the blood circulation. However, the lymphatic system
      also provides the means for immune surveillance in the immune system, acting as
      conduits that convey soluble antigens and antigen-presenting cells from the
      tissues to the lymph nodes, where primary lymphocyte responses are generated. One
      macromolecule that potentially unites these two functions is the large
      extracellular matrix glycosaminoglycan hyaluronan (HA), a chemically simple
      copolymer of GlcNAc and GlcUA that fulfills a diversity of functions from danger
      signal to adhesive substratum, depending upon chain length and particular
      interaction with its many different binding proteins and a small but important
      group of receptors. The two most abundant of these receptors are CD44, which is
      expressed on leukocytes that traffic through the lymphatics, and LYVE-1, which is
      expressed almost exclusively on lymphatic endothelium. Curiously, much of the HA
      within the tissues is turned over and degraded in lymph nodes, by a poorly
      understood process that occurs in the medullary sinuses. Indeed there are several
      mysterious aspects to HA in the lymphatics. Here we cover some of these by
      reviewing recent findings in the biology of lymphatic endothelial cells and their
      possible roles in HA homeostasis together with fresh insights into the complex
      and enigmatic nature of LYVE-1, its regulation of HA binding by sialylation and
      self-association, and its potential function in leukocyte trafficking.

PMID- 19594641
TI  - Modulation of host immune responses by helminth glycans.
AB  - Parasitic infections regulate/alter host immune responses. Among parasitic
      infections, helminth infection often leads to systemic immune suppression or
      anergy. Helminth infection or helminth extracts drive CD4+ T-helper (Th) cell
      responses towards Th2 type and activate antigen-presenting cells (APCs) such that
      these cells express an anti-inflammatory phenotype. Among the myriad molecules
      present on or secreted by helminth parasites, glycans have been shown to be key
      in inducing Th2-type and anti-inflammatory immune responses. The majority of
      studies on immune modulatory helminth glycans have focused on Lacto-N
      fucopentaose III and LewisX. When presented as glycol-conjugates, with multiple
      copies of the sugars conjugated to a carrier molecule, these compounds activate
      APCs, inducing an alternative activation pattern, whose phenotypic profile is
      substantially different than that seen using pro-inflammatory activators such as
      lipopolysaccharide. Though the mechanism of APC activation by LNFPIII/LewisX
      glycoconjugates has not been fully elucidated, it involves C-type lectin ligation
      on the surface of APCs, with subsequent antagonism of Toll-like receptor
      signaling. In this article, we discuss the APC surface receptors known to play
      roles in LNFPIII/LewisX induced alternative activation of APCs. We also discuss
      what is currently known regarding downstream signaling pathways, closing with a
      discussion of future research directions for this field of investigation
      including the potential use of immune modulatory glycans as vaccine adjuvants and
      anti-inflammatory therapeutics.

PMID- 19594642
TI  - Building a caring society.

PMID- 19594640
TI  - T-cell growth, cell surface organization, and the galectin-glycoprotein lattice.
AB  - Basal, activation, and arrest signaling in T cells determines survival,
      coordinates responses to pathogens, and, when dysregulated, leads to loss of self
      tolerance and autoimmunity. At the T-cell surface, transmembrane glycoproteins
      interact with galectins via their N-glycans, forming a molecular lattice that
      regulates membrane localization, clustering, and endocytosis of surface
      receptors. Galectin-T-cell receptor (TCR) binding prevents ligand-independent TCR
      signaling via Lck by blocking spontaneous clustering and CD4-Lck recruitment to
      TCR, and in turn F-actin transfer of TCR/CD4-Lck complexes to membrane
      microdomains. Peptide-major histocompatibility complexes overcome galectin-TCR
      binding to promote TCR clustering and signaling by Lck at the immune synapse.
      Galectin also localizes the tyrosine phosphatase CD45 to microdomains and the
      immune synapse, suppressing basal and activation signaling by Lck. Following
      activation, membrane turnover increases and galectin binding to cytotoxic T
      lymphocyte antigen-4 (CTLA-4) enhances surface expression by inhibiting
      endocytosis, thereby promoting growth arrest. Galectins bind surface
      glycoproteins in proportion to the branching and number of N-glycans per protein,
      the latter an encoded feature of protein sequence. N-glycan branching is
      conditional to the activity of Golgi N-acetylglucosaminyl transferases I, II, IV
      and V (Mgat1, 2, 4, and 5) and metabolic supply of their donor substrate UDP
      GlcNAc. Genetic and metabolic control of N-glycan branching co-regulate
      homeostatic set-points for basal, activation, and arrest signaling in T cells
      and, when disturbed, result in T-cell hyperactivity and autoimmunity.

PMID- 19594643
TI  - Duly Authorized Officers' practices under mental health law in New Zealand: Are
      nurses meeting the requirements of the law?
AB  - The Mental Health (Compulsory Assessment and Treatment) Act (1992) introduced a
      number of statutory roles that are undertaken by mental health nurses. One of
      these roles is that of Duly Authorized Officer (DAO). The DAO is responsible for
      the procedural requirements necessary to facilitate compulsory assessment. Under
      Section 9(2)(d), the DAO is required to ensure that the purpose of the assessment
      and the requirements of the notice of assessment are explained to the person in
      the presence of a member of their family, a caregiver, or other person concerned
      with the welfare of the person. Three recent High Court decisions under the
      Habeas Corpus Act 2001 have challenged existing DAO practices in arranging the
      presence of a third party. This paper presents research, which focuses on
      unravelling some of the complexities associated with meeting this procedural
      requirement. It illustrates these complexities through a discussion of the
      results of an audit of files and three focus groups with mental health nurses who
      practise as DAO. The paper concludes that national guidelines for practice need
      to be developed for DAO to assist mental health nurses in meeting this statutory
      requirement.

PMID- 19594644
TI  - Cochrane Reviews of non-medication-based psychotherapeutic and other
      interventions for schizophrenia, psychosis, and bipolar disorder: A systematic
      literature review.
AB  - Mental health-care professionals are striving to keep up to date with health
      interventions that are effective and beneficial to patients. The Cochrane Reviews
      make available a systematic and up-to-date review of a comprehensive range of
      health interventions. We identified a total of 28 interventions from a systematic
      search and review of the Cochrane Reviews for either schizophrenia, psychosis,
      schizoaffective, or bipolar disorder. These interventions have been graded into
      tables of: strong support that merits application, moderate support that warrants
      consideration of application, not supported, and data that is deemed
      inconclusive. The tables provide a comprehensive summary and classification of
      evidence-based practices. This information is presented in a way to enable nurses
      and other health-care professionals to analyze their own practices to improve
      mental health services and outcomes for patients. Of the 28 interventions
      identified in this review, four had strong support and five had moderate support
      meriting application. Limitations of this review are discussed.

PMID- 19594645
TI  - Empirical studies of clinical supervision in psychiatric nursing: A systematic
      literature review and methodological critique.
AB  - The objective of this paper was to systematically review and critically evaluate
      all English language research papers reporting empirical studies of clinical
      supervision in psychiatric nursing. The first part of the search strategy was a
      combination of brief and building block strategies in the PubMed, CINAHL, and
      PsycINFO databases. The second part was a citation pearl growing strategy with
      reviews of 179 reference lists. In total, the search strategy demonstrated a low
      level of precision and a high level of recall. Thirty four articles met the
      criteria of the review and were systematically evaluated using three checklists.
      The findings were summarized by using a new checklist with nine overall questions
      regarding the studies' design, methods, findings, and limitations. The studies
      were categorized as: (i) effect studies; (ii) survey studies; (iii) interview
      studies; and (iv) case studies. In general, the studies were relatively small
      scale; they used relatively new and basic methods for data collection and
      analysis, and rarely included sufficient strategies for identifying confounding
      factors or how the researchers' preconceptions influenced the analyses. Empirical
      research of clinical supervision in psychiatric nursing was characterized by a
      basic lack of agreement about which models and instruments to use. Challenges and
      recommendations for future research are discussed. Clinical supervision in
      psychiatric nursing was commonly perceived as a good thing, but there was limited
      empirical evidence supporting this claim.

PMID- 19594646
TI  - Transition to psychiatric/mental health nursing programs: Expectations and
      practical considerations.
AB  - Mental health services have developed transition programs to attract staff,
      including new graduates, staff with mental health nursing experience without
      formal qualifications, experienced nurses wishing to move into mental health, and
      nurses returning to the workforce. Transition to psychiatric/mental health
      programs are considered to be particularly significant in the mental health field
      because of the relative under-representation of mental health content in
      undergraduate curricula. Unfortunately, transition programs have received only
      minor attention in the literature and there is a paucity of published evaluations
      to determine their effectiveness. The aim of this paper is to examine transition
      programs and consider how they meet the expectations of stakeholders, such as
      consumers of mental health services, and program participants' expectations. It
      is concluded that published systematic evaluations are lacking, particularly
      those considered from the perspective of stakeholders. Consideration of these
      expectations should be reflected in the design and delivery of mental health
      nursing transition programs.

PMID- 19594647
TI  - Negotiating complexities: An ethnographic study of intellectual disability and
      mental health nursing in New Zealand.
AB  - This paper presents the findings from a study undertaken to describe nursing
      practice in one dual diagnosis (DD; coexisting mental illness and intellectual
      disability) inpatient unit in New Zealand. A focused ethnographic approach (using
      fieldwork observations, a review of documents, and five semistructured
      interviews) was used to gather data. A model of culture was used to analyze data
      to allow a description of DD nursing practice. Additionally, this framework
      allowed for an exploration of the artefacts, values, and assumptions that
      underpin these practices. Three key themes emerged from the data: keeping
      everyone safe, managing the complexities in assessment, and narrating their work.
      Together, these themes indicate that in the absence of a defined model of DD
      nursing, practice is based on an institutional psychiatric model. We argue that
      DD nursing models need to be made explicit in order to advance nursing in this
      area.

PMID- 19594648
TI  - Effect of music on depression levels and physiological responses in community
      based older adults.
AB  - Many people over the age of 65 do not regard depression as a treatable mental
      disorder and find it difficult to express themselves verbally. Listening to music
      can facilitate the non-verbal expression of emotion and allow people's inner
      feelings to be expressed without being threatened. The aim of this study was to
      determine the effect of music on depression levels in elderly people. A
      randomized controlled study was conducted with 47 elderly people (23 using music
      and 24 controls) who completed the study after being recruited in Hong Kong.
      Blood pressure, heart rate (HR), respiratory rate (RR), and depression level
      variables were collected. In the music group, there were statistically
      significant decreases in depression scores (P < 0.001) and blood pressure (P =
      0.001), HR (P < 0.001), and RR (P < 0.001) after 1 month. The implication is that
      nurses may utilize music as an effective nursing intervention for patients with
      depressive symptoms in the community setting.

PMID- 19594649
TI  - Horizontal violence.

PMID- 19594652
TI  - The unique role of advanced practice nurses at the National Institutes of Health:
      Results of a 2006 survey.
AB  - PURPOSE: To characterize the role of advanced practice nurses (APNs),
      particularly nurse practitioners (NPs), in the practice setting of the National
      Institutes of Health (NIH), a Federal biomedical research facility. DATA SOURCES:
      APNs with prescriptive authority employed at the NIH were surveyed using an
      adaptation of the American Academy of Nurse Practitioners (AANP) "2004 Nurse
      Practitioner Sample Survey." A total of 56 of 93 surveys were returned (63%
      response rate), and of these, 54 (96%) were completed by NPs. CONCLUSION: In the
      20 years they have been at NIH, the number of NPs has grown from less than 10 to
      more than 100. NIH NPs combine clinical research responsibilities with the
      provision of comprehensive medical management to patients enrolled on NIH
      protocols, blending clinical, research, educational, and administrative tasks
      into a unique and multifaceted role. There is a high level of satisfaction among
      NPs employed at the NIH, and they are considered an integral part of the research
      team. IMPLICATIONS FOR PRACTICE: This survey shows the variability in practice
      opportunities available to NPs in a research environment and the impact they have
      on public health.

PMID- 19594653
TI  - What do you mean you want me to teach, do research, engage in service, and
      clinical practice? Views from the trenches: The novice, the expert.
AB  - The purpose of this column is to explicate two points of view-the novice and the
      expert nurse practitioner (NP) faculty member, highlighting the importance of
      mentoring new faculty NP members into the diverse faculty roles relating to both
      general academic requirements and those particular roles related to NP education.
      For example, arranging clinical placements is one of the most important and time
      consuming responsibilities of NP faculty. Learning to juggle all the roles is a
      challenge to new faculty members. Such mentoring may help alleviate the
      phenomenon of young faculty members leaving academia and returning to full-time
      clinical practice. Mentoring is crucial to integrating new NP faculty members
      into academic life.

PMID- 19594654
TI  - Managing high-acuity-depressed adults in primary care.
AB  - PURPOSE: To identify strategies for managing high-acuity-depressed adults in
      primary care settings. Patients who do not achieve remission with initial
      treatment, patients at risk for suicide, and patients with co-occurring substance
      use disorders are specifically addressed. DATA SOURCES: Scientific literature and
      evidence-based practice guidelines. CONCLUSION: Accurate diagnosis is best
      accomplished using screening instruments as an adjunct to a thorough history and
      assessment. The goal of interventions is remission of symptoms as opposed to a
      partial response. Patient preferences regarding choice of intervention must be
      considered. Initial pharmacotherapy must include adequate doses and a trial of
      adequate duration. Patients who do not respond to two medication trials are at
      risk for suicide and/or have a co-occurring substance use disorder may require:
      (a) a combination of medications coupled with psychotherapy; or (b) referral to
      mental health specialists to achieve the best outcomes. IMPLICATIONS FOR
      PRACTICE: High-acuity patients with mental health needs will continue to be seen
      in primary care settings. Through educational preparation and a patient-centered
      focus, advanced practice nurses in primary care settings are in an optimal
      position to set a high standard of care for complex mental health patients.

PMID- 19594655
TI  - Chest pain with angiographic clear coronary arteries: A provider's approach to
      cardiac syndrome X.
AB  - PURPOSE: To present information about cardiac syndrome X (CSX) including its (a)
      definition, (b) etiology and pathology, (c) epidemiology, (d) symptomatology, (e)
      diagnosis, (f) treatment, and (g) prognosis. Clinical recommendations will also
      be presented. DATA SOURCES: Articles used in this review were found by searching
      CINAHL, Medline, the Cochrane Library, Web of Science (ISI), Academic Search
      Premier, and Health Source: Nursing/Academic Edition. CONCLUSIONS: The causes of
      CSX remain unknown; however, CSX is easy to diagnose and can be treated.
      Medication therapy and risk factor modification can greatly improve the quality
      of life by decreasing pain occurrence and lessening pain intensity. IMPLICATIONS
      FOR PRACTICE: Too often, providers reassure patients of a healthy heart because
      of normal coronary arteries despite persistent chest pain and ST segment changes
      on the electrocardiogram. Chest pain, one of the primary signs and symptoms of
      CSX, can be reduced through common medications and interventions if the diagnosis
      of CSX is initiated.

PMID- 19594657
TI  - Advanced practice nursing: A principle-based concept analysis.
AB  - PURPOSE: To analyze and clarify the conceptual basis of advanced practice nursing
      to determine the state of the knowledge from the perspective of four overarching
      principles derived from the philosophy of science: epistemological, pragmatic,
      linguistic, and logical. DATA SOURCES: Written discourse regarding advanced
      practice nursing from refereed journals published between 2000 and 2007.
      CONCLUSIONS: Conceptualization of a core definition of advanced practice nursing
      will enhance external legitimacy and recognition; understanding advanced practice
      nurse (APN) roles, sub-roles, and competencies will enhance internal cohesion.
      The outcome of this concept analysis is a greater understanding of the conceptual
      basis of advanced practice nursing and a current best estimate of the probable
      truth surrounding advanced practice nursing. IMPLICATIONS FOR PRACTICE: A greater
      understanding of the conceptual basis of advanced practice nursing will help to
      gain clarity, internal cohesion, external legitimacy, and acceptance of APN roles
      by society and other healthcare professions.

PMID- 19594656
TI  - Feasibility of a patient-driven approach to recruiting older adults, caregivers,
      and clinicians for provider-patient communication research.
AB  - PURPOSE: This report describes the implementation of a novel, patient-driven
      approach to recruitment for a study of interpersonal communication in a primary
      care setting involving persons with Alzheimer's disease (AD), their family
      caregivers, and their primary care providers (PCPs). DATA SOURCES: Patients and
      caregivers were centrally recruited from a university-based memory clinic,
      followed by the recruitment of patient's individual PCPs. Recruitment tracking,
      naturalistic observation, and survey methods were used to evaluate recruitment
      success. CONCLUSIONS: About half of the patients and caregivers (n = 54; 51%) and
      most of the PCPs (n = 31; 76%) who we approached agreed to an audiorecording of
      the patient's next PCP visit. Characteristics of patient, caregiver, and PCP
      participants were compared to those of nonparticipants. Patient characteristics
      did not differ by participation status. Caregivers who volunteered for the study
      were more likely to be female and married than were those who declined to
      participate. Compared to nonparticipants, PCPs who agreed to the study were
      appraised slightly more favorably by patients' caregivers on a measure of
      satisfaction with care on the day of the visit. The vast majority of
      participating PCPs (95%) reported that the study had little or no impact on the
      flow of routine clinical operations. IMPLICATIONS FOR RESEARCH: Findings support
      the feasibility of a patient-driven approach to recruitment for studies involving
      multiple linked participants. Our discussion highlights possible advantages of
      such an approach, including the potential to empower patient participants while
      achieving maximum variability within the pool of clinician participants.

PMID- 19594658
TI  - Obsessive-compulsive disorder in children: The role of nurse practitioners.
AB  - PURPOSE: To review the characteristics of obsessive-compulsive disorder (OCD) in
      children, differential diagnoses, screening and assessment tools, interventions,
      and outcomes. The role of nurse practitioners (NPs) in caring for children with
      OCD and the need for more research are discussed. DATA SOURCES: Review of
      published literature on the topic. CONCLUSIONS: OCD is now recognized as a common
      psychiatric disorder that may go unrecognized during childhood, leading to
      interference with a child's development and daily functioning. Early
      identification and treatment of OCD are crucial for a child's psychosocial
      functioning and quality of life. IMPLICATIONS FOR PRACTICE: NPs familiar with OCD
      in children can identify patients and make informed judgments about assessment,
      treatment, and referral.

PMID- 19594659
TI  - Hypertensive management in the elderly patient at risk for falls.
AB  - PURPOSE: Seventy percent of people over 65 years of age have hypertension, and
      one third of elders fall each year. These conditions frequently coexist, and each
      carries a risk for substantial functional decline or mortality. This article
      reviews the risks of and interventions to reduce falls in the elderly patient
      with hypertension. DATA SOURCES: A systematic review of the published and
      unpublished literature and consensus panel recommendations through January 2008
      are discussed. CONCLUSIONS: Hypertension management in the frail elder at risk
      for fall must include a thoughtful assessment of the relative risks and benefits
      of treatments that are most likely to preserve function, independence, and
      quality of life. Stringent adherence to guidelines may not be appropriate for all
      patients. The periodic use of a standardized fall risk screening tool can assist
      the nurse practitioner (NP) to identify patients at risk for falls and adjust
      medication management accordingly. IMPLICATIONS FOR PRACTICE: This article will
      assist the NP to weigh management options in the context of the complex elderly
      patient.

PMID- 19594660
TI  - Importance of climatic and environmental change in the demography of a multi
      brooded passerine, the woodlark Lullula arborea.
AB  - 1. We examined the influence of local weather conditions on reproductive success,
      timing of breeding and survival in a population of a multi-brooded ground nesting
      passerine (woodlark Lullula arborea) over 35 years. 2. Woodlarks laid larger
      clutches when rainfall was low and temperature high during the egg-laying and pre
      laying period. Nest success increased with higher temperatures during the nesting
      period. In successful nests, the number of chicks fledged per egg laid was
      greater when weather was drier during the brood stage. 3. Although woodlarks bred
      earlier in years with warmer early spring temperatures, with the onset of
      breeding varying by 25 days, there was no significant advance in the onset of
      breeding over the 35 years of study, due to considerable inter-annual
      variability, and no overall trend, in weather. 4. Simulation modelling of annual
      reproductive output demonstrated that earlier breeding could increase
      productivity by 23.5% in the warmest compared to the coldest year, due to birds
      having more nesting attempts. Other effects of weather on productivity affected
      breeding output to a lesser extent. 5. Effects of weather on productivity were
      minor compared to an increased rate of nest predation through the period of
      study, which reduced productivity by 49.8% by 2004 compared to 1971. 6. Turning
      points analysis identified three distinct demographic periods: from 1971 to 1988
      the population grew slowly, during 1988-1999 the population grew rapidly, but
      after 1999 the population declined. Increased population growth after 1988 was
      associated with higher first-year survival rates (estimated using a population
      model). Population decline after 1999 was caused by a combination of reduced
      productivity (resulting from increased nest failure rates attributed to
      predation) and lower first-year survival rates, that appear unrelated to winter
      temperature. 7. Climate change (long-term changes in weather) did not explain the
      marked changes observed in the population trajectory over 35 years. We suggest
      that understanding effects of both climate and habitat change on populations is
      essential in predictive population modelling.

PMID- 19594661
TI  - Spatial scale and opportunities for choice influence browsing and associational
      refuges of focal plants.
AB  - 1. Foraging decisions by herbivores depend on variation in food types, the
      scale(s) at which this variation occurs and the opportunity and capacity for
      herbivores to respond to such variation. These decisions affect not only the
      herbivores themselves, but also the vulnerability of individual plants to being
      eaten. Associational plant refuges, in which neighbouring plants alter focal
      plant vulnerability, are an emergent property of foraging decisions. 2. Using the
      red-bellied pademelon (Thylogale billardierii) as a model generalist mammalian
      herbivore, we investigated the spatial scale(s) at which animals made foraging
      decisions and the resultant effect on focal plant vulnerability. In a replicated
      design, we varied vegetation at the individual plant scale, generating
      intraspecific differences in Eucalyptus nitens seedlings by altering their
      nutrient status (high, low). We varied vegetation at the patch scale, in which
      seedlings were planted, using high- (grass) and low- (herbicided) quality
      patches. Animals were allowed to choose where they fed and what they ate. Animal
      behaviour was recorded and intake of seedlings measured. 3. We found that animals
      made foraging decisions first at the patch scale then at the scale of individual
      plants; both patch and focal seedling characteristics influenced browsing.
      Pademelons spent most of their time in high-quality patches, and seedlings were
      consequently more vulnerable there than in low-quality patches. Pademelons also
      ate more foliage from high- than from low-nutrient status seedlings. This
      behaviour concentrated resources, increasing foraging efficiency and making focal
      plants more vulnerable to browsing. 4. The opportunity and capacity to choose at
      both plant and patch scales resulted in a pattern of focal plant vulnerability
      consistent with the repellent-plant hypothesis. This contrasts with our previous
      study, in which animals were only provided with choice at the plant level and
      plant vulnerability followed the attractant-decoy hypothesis. These combined
      results demonstrate that the influence of neighbouring vegetation on consumption
      of a focal plant depends on the spatial scale of selection and on opportunities
      (and capacity) for herbivores to choose.

PMID- 19594662
TI  - Testing a biological mechanism of the insurance hypothesis in experimental
      aquatic communities.
AB  - 1. The insurance hypothesis predicts a stabilizing effect of increasing species
      richness on community and ecosystem properties. Difference among species'
      responses to environmental fluctuations provides a general mechanism for the
      hypothesis. Previous experimental investigations of the insurance hypothesis have
      not examined this mechanism directly. 2. First, responses to temperature of four
      protist species were measured in laboratory microcosms. For each species, we
      measured the response of intrinsic rate of increase (r) and carrying capacity (K)
      to temperature. 3. Next, communities containing pairs of species were exposed to
      temperature fluctuations. Community biomass varied less when correlation in K
      between species (but not r) was more negative, and this resulted from more
      negative covariances in population sizes, as predicted. Results were contingent
      on species identity, with findings differing between analyses including or not
      including communities containing one particular species. 4. These findings
      provide the clearest support to date for this mechanism of the insurance
      hypothesis. Biodiversity, in terms of differences in species' responses to
      environmental fluctuations (i.e. functional response diversity) stabilizes
      community dynamics.

PMID- 19594663
TI  - Connective tissue graft plus resin-modified glass ionomer restoration for the
      treatment of gingival recession associated with non-carious cervical lesion: a
      randomized-controlled clinical trial.
AB  - BACKGROUND: The aim of this clinical study was to evaluate the treatment of
      gingival recession, associated with non-carious cervical lesions by a connective
      tissue graft (CTG) alone, or in combination with a resin-modified glass ionomer
      restoration (CTG+R). MATERIALS AND METHODS: Forty patients presenting Miller
      Class I buccal gingival recessions, associated with non-carious cervical lesions,
      were selected. The defects were randomly assigned to receive either CTG or CTG+R.
      Bleeding on probing (BOP), probing depth (PD), relative gingival recession (RGR),
      clinical attachment level (CAL) and cervical lesion height (CLH) coverage were
      measured at baseline and 45 days, and 2, 3 and 6 months after treatment. RESULTS:
      Both groups showed statistically significant gains in CAL and soft tissue
      coverage. The differences between groups were not statistically significant in
      BOP, PD, RGR and CAL, after 6 months. The percentages of CLH covered were 74.88
      +/- 8.66% for CTG and 70.76 +/- 9.81% for CTG+R (p>0.05). The estimated root
      coverage was 91.91 +/- 17.76% for CTG and 88.64 +/- 11.9% for CTG+R (p>0.05).
      CONCLUSION: Within the limits of the present study, it can be concluded that both
      procedures provide comparable soft tissue coverage. The presence of the glass
      ionomer restoration may not prevent the root coverage achieved by CTG.

PMID- 19594664
TI  - Sonographic biometrical normograms and estimation of fetal weight in the baboon
      (Papio anubis).
AB  - BACKGROUND: In order to consider the non-human primate as an adequate model for
      studying prenatal diagnosis and therapy, comparative data on fetal growth should
      be available. METHODS: Sixty ultrasound scans were performed in 22 baboons
      between 14 and 167 days of gestation. MEASUREMENTS: included greatest length,
      head circumference, biparietal diameter (BPD), transcerebellar diameter,
      abdominal circumference (AC), femur length (FL), and amniotic fluid index. For
      all parameters growth curves were established and compared with human curves. In
      18 animals, birth weight and placental weight were determined. Different
      equations described in the literature for estimating the human fetal weight were
      tested in the baboon. RESULTS: The fetal and placental growth pattern in the
      baboon was comparable with humans. The best predictor of fetal weight was the
      formula presented by Combs: 0.23966 x AC(2) x FL + 1.623 x BPD(3). CONCLUSIONS: A
      high similarity between baboon and human growth charts is shown. The best
      equation for estimating the baboon fetal weight is proposed.

PMID- 19594665
TI  - Regulation of exocytotic protein expression and Ca2+-dependent peptide secretion
      in astrocytes.
AB  - Vesicular transmitter release from astrocytes influences neuronal development,
      function and plasticity. However, secretory pathways and the involved molecular
      mechanisms in astroglial cells are poorly known. In this study, we show that a
      variety of SNARE and Munc18 isoforms are expressed by cultured astrocytes, with
      syntaxin-4, Munc18c, SNAP-23 and VAMP-3 being the most abundant variants.
      Exocytotic protein expression was differentially regulated by activating and
      differentiating agents. Specifically, proteins controlling Ca(2+)-dependent
      secretion in neuroendocrine cells were up-regulated after long-term 8Br-cAMP
      administration in astrocytes, but not by proinflammatory cytokines. Moreover, 8Br
      cAMP treatment greatly increased the cellular content of the peptidic vesicle
      marker secretogranin-2. Release assays performed on cAMP-treated astrocytes
      showed that basal and stimulated secretogranin-2 secretion are dependent on
      [Ca(2+)](i). As shown release of the chimeric hormone ANP.emd from transfected
      cells, cAMP-induced differentiation in astrocytes enhances Ca(2+)-regulated
      peptide secretion. We conclude that astroglial cells display distinctive
      molecular components for exocytosis. Moreover, the regulation of both exocytotic
      protein expression and Ca(2+)-dependent peptide secretion in astrocytes by
      differentiating and activating agents suggest that glial secretory pathways are
      adjusted in different physiological states.

PMID- 19594666
TI  - Condition dependence varies with mating success in male Drosophila bunnanda.
AB  - Although key to sexual selection theories, condition dependence has proven a
      challenging area of empirical research. It is expected that availability of
      resources will affect both mean and variation of sexual trait expression, with
      lower mean and greater variation in harsher environments. Here, I manipulated the
      environment in a laboratory population of Drosophila bunnanda to test for
      condition dependence of sexually selected traits. Sexually successful and
      unsuccessful males differed in how the environment affected sexual trait
      expression. Specifically, sexual trait attractiveness declined more rapidly with
      declining resources in sexually unsuccessful males, consistent with the
      expectation that low quality males were less able to meet the greater signalling
      costs associated with harsher environments. This study illustrates the potential
      insights into condition dependence that might be gained through considering
      sexual trait expression and mating success within the same manipulative
      experimental design.

PMID- 19594671
TI  - A decade of stigma and discrimination in mental health: plus ca change, plus
      c'est la meme chose (the more things change, the more they stay the same).
AB  - In recent years, efforts to combat stigma and discrimination experienced by
      mental health service users have ranged from small local initiatives to national
      and international campaigns. Success has been mixed, with significant, lasting
      benefits appearing to be elusive. This paper explores the current nature and
      extent of stigma and discrimination in an area of the north of England and
      compares findings with those from a study undertaken a decade previously in 1997.
      Qualitative responses to a postal questionnaire received in 2007 were
      thematically analysed and compared and contrasted with findings from the 1997
      study. Four broad categories of discrimination--(1) employment; (2) professional;
      (3) communities; and (4) family and friends--arose from the 2007 data, the most
      common being discrimination in employment. There were close similarities in both
      sets of data. Stigma and discrimination remain largely as strong, damaging and
      enduring as they were a decade ago. A range of pre-emptive interventions that
      support people prior to the escalation of mental health crises could limit the
      impact of stigma.

PMID- 19594667
TI  - Event-related FMRI of inhibitory control in the predominantly inattentive and
      combined subtypes of ADHD.
AB  - BACKGROUND AND PURPOSE: To examine the neurophysiological basis for the
      pronounced differences in hyperactivity and impulsiveness that distinguish the
      predominantly inattentive type of attention-deficit/hyperactivity disorder (ADHD
      PI) from the combined type of the disorder (ADHD-C). METHODS: Event-related brain
      responses to a go/no-go test of inhibitory control were measured with functional
      magnetic resonance imaging (fMRI) in 11 children with ADHD-C and 9 children with
      ADHD-PI, aged 7 to 13 years, who were matched for age, sex, and intelligence.
      RESULTS: There were no significant group differences in task performance.
      Children with ADHD-C and ADHD-PI activated overlapping regions of right inferior
      frontal gyrus, right superior temporal lobe, and left inferior parietal lobe
      during inhibitory control. However, the magnitude of the activation in the
      temporal and parietal regions, as well as in the bilateral middle frontal gyrus,
      was greater in children with ADHD-PI than those with ADHD-C. Conversely, children
      with ADHD-C activated bilateral medial occipital lobe to a greater extent than
      children with ADHD-PI. CONCLUSIONS: The results provide preliminary evidence that
      phenotypic differences between the ADHD-C and ADHD-PI subtypes are associated
      with differential activation of regions that have previously been implicated in
      the pathophysiology of ADHD and are thought to mediate executive and attentional
      processes.

PMID- 19594672
TI  - Independent mental health nurse prescribing.
AB  - Independent prescribing (IP) is a new form of prescriptive authority for mental
      health services. Very little is known about where IP is being implemented and
      factors to support or constrain its adoption. An opportunistic sample of 119
      respondents made up of nurses, doctors, support workers, occupational therapists
      and social workers completed an online survey. The sample worked in adult, old
      age and substance misuse services. Hospital wards and community mental health
      teams were identified as the highest ranked areas for implementation. A total of
      68% of the sample identified pharmacology as the area for further training. And
      40% of the sample felt that IP had been introduced to make services more
      effective. This opportunistic sample supported IP as a means to offer greater
      patient choice and as a method to broaden the boundaries of nursing practice.
      Integral to this development is the link between the psychiatrist and IP nurse in
      terms of work allocation and supervision.

PMID- 19594674
TI  - Service users' experiences of a therapeutic group programme in an acute
      psychiatric inpatient unit.
AB  - Psychiatric nurses have been facilitating therapeutic groups in acute psychiatric
      inpatient units for many years; however, there is a lack of nursing research
      related to this important aspect of care. This paper reports the findings of a
      study which aimed to gain an understanding of service users' experiences in
      relation to therapeutic group activities in an acute inpatient unit. A
      qualitative descriptive study was undertaken with eight service users in one
      acute psychiatric inpatient unit in Ireland. Data were collected using in-depth
      semi-structured interviews and analysed using Burnard's method of thematic
      content analysis. Several themes emerged from the findings which are presented in
      this paper.

PMID- 19594673
TI  - Are stigma experiences among persons with mental illness, related to perceptions
      of self-esteem, empowerment and sense of coherence?
AB  - The aim of the study was to explore the relationship between stigmatizing
      rejection experiences and self-related variables. Our hypothesis was that
      rejection experiences would be negatively associated with perceptions of self
      esteem, empowerment and sense of coherence. A cross-sectional study assessing
      rejection experiences, empowerment, sense of coherence and self-esteem was
      performed, including 200 persons in current or earlier contact with mental health
      services. The results showed that experiences of rejection were negatively
      associated with sense of coherence, empowerment and self-esteem. This exploratory
      investigation suggests that experiences of rejection might be a target for coping
      interventions. Mental health nurses are in a key position to identify patients'
      experiences of stigma and by that to understand what consequences of
      devaluation/discrimination can have for the afflicted.

PMID- 19594675
TI  - Hardship, dedication and investment: an exploration of Irish mothers commitment
      to communicating with their children with cerebral palsy.
AB  - This qualitative study investigated the experiences of mothers who have a child
      with communication difficulties resulting from cerebral palsy (CP). There is a
      dearth of information about parents' experiences of having a child with CP and
      communication difficulties. Three participants, whose children had moderate or
      severe CP and communication difficulties, were recruited from a voluntary
      organization. Participants were interviewed using an in-depth, semi-structured
      interview guide. Interviews were audio-recorded, then transcribed and
      subsequently analysed using Grounded Theory methods. Five main themes emerged,
      combining to form the core category of mothers dedicating their attention to
      their children. The information gleaned from this study could have important
      implications for nurses involved in facilitating communication, including speech
      and language therapists, occupational therapists and registered nurses. By
      becoming more aware of the experiences of parents with a child with CP and
      communication disorders, nurses may be better able to plan and implement therapy
      and also support communication aims. The study concludes with a discussion of
      further research avenues, suggesting that a study investigating the experiences
      of parents of children with other types of physical disabilities affecting
      communication should be conducted to determine the similarities and differences
      of parents of children with other kinds of disability. A similar study with a
      larger sample could be conducted to validate the findings of the current study.

PMID- 19594676
TI  - Knowledge and attitudes of mental health professionals in Ireland to the concept
      of recovery in mental health: a questionnaire survey.
AB  - Recovery is the model of care presently advocated for mental health services
      internationally. The aim of this study was to examine the knowledge and attitudes
      of mental health professionals to the concept of recovery in mental health. A
      descriptive survey approach was adopted, and 153 health care professionals
      (nurses, doctors, social workers, occupational therapists and psychologists)
      completed an adapted version of the Recovery Knowledge Inventory. The respondents
      indicated their positive approach to the adoption of recovery as an approach to
      care in the delivery of mental health services. However, respondents were less
      comfortable in encouraging healthy risk taking with service users. This finding
      is important because therapeutic risk taking and hope are essential aspects in
      the creation of a care environment that promotes recovery. Respondents were also
      less familiar with the non-linearity of the recovery process and placed greater
      emphasis on symptom management and compliance with treatment. Multidisciplinary
      mental health care teams need to examine their attitudes and approach to a
      recovery model of care. The challenge for the present and into the future is to
      strive to equip professionals with the necessary skills in the form of
      information and training.

PMID- 19594677
TI  - Quality of life for patients with schizophrenia living in the community in
      Greece.
AB  - Several quality of life instruments were considered for use in a Greek mental
      health environment. Subjective Quality of Life Profile was chosen as it was easy
      to complete and covered the issues raised by patients with schizophrenia through
      interviews. Confirmatory factor analysis gave credence to the four-dimensional
      structure identified by the original authors. Patients with schizophrenia were
      generally satisfied with their quality of life, found the items in the instrument
      important and were optimistic about expectations for change. Age, gender,
      education, marital status and years of sickness were not statistically
      significant in a general linear model with quality of life as the outcome for the
      27 core questions. There were some statistically significant results for the
      three disease-specific questions; positive expectation was correlated positively
      with education and negatively with years of sickness.

PMID- 19594678
TI  - The growing role of football as a vehicle for interventions in mental health
      care.
AB  - In recent years there has been a growing interest in the use of football as a
      vehicle for mental health interventions. This paper outlines some of the ways
      that mental health service providers have begun to develop strategies with
      football clubs, the Football Association and government departments that involve
      playing or watching football and placing mental health services in football
      clubs. The paper also looks at how some attempts are being made at regional and
      national levels to develop and bring together services that use football as a
      vehicle for mental health service delivery.

PMID- 19594679
TI  - Stigma, negative attitudes and discrimination towards mental illness within the
      nursing profession: a review of the literature.
AB  - The aim of this paper was to review the existing literature pertaining to stigma,
      negative attitudes and discrimination towards mental illness, specifically as
      viewed through the lens of the nursing profession. The results of the literature
      review were synthesized and analysed, and the major themes drawn from this were
      found to correspond with Schulze's model identifying three positions that
      healthcare workers may assume in relation to stigma of mental illness:
      'stigmatizers', 'stigmatized' and 'de-stigmatizers'. In this paper, the nursing
      profession is examined from the perspectives of the first two major themes: the
      'stigmatizers' and 'stigmatized'. Their primary sub-themes are identified and
      discussed: (1) Nurses as 'the stigmatizers': (a) nurses' attitudes in general
      medical settings towards patients with psychiatric illness and (b) psychiatric
      nurses; (2) Nurses as 'the stigmatized': (a) nurses who have mental illness and
      (b) stigma within the profession against psychiatric nurses and/or psychiatry in
      general. The secondary and tertiary sub-themes are also identified and reviewed.

PMID- 19594680
TI  - An opportunity to serve.

PMID- 19594681
TI  - HEART--the Hounslow Early Active Recovery Team: implementing an inclusive
      strength-based model of care for people with early psychosis.
AB  - In recent years in the UK, the National Health Service has made policy
      commitments to delivering mental health services based on recovery principles. In
      general though, the UK mental health service providers are in the early stages of
      implementing recovery principles and approaches in front-line services. This
      paper describes the work of the Hounslow Early Active Recovery Team (HEART),
      which has made substantial progress in placing recovery principles and approaches
      at the heart of the work of an early intervention for psychosis team working in
      an ethnically diverse area of West London. As evidence of the success of the
      HEART, in its first year and half, the team has achieved high levels of customer
      satisfaction with its work and a recent audit has revealed that 57% of
      respondents were in employment or education contrasting with the extremely high
      unemployment rates reported in several UK studies of people with serious mental
      health problems.

PMID- 19594682
TI  - Does the use of a physical health assessment tool improve the physical health of
      clients of a community mental health team?

PMID- 19594683
TI  - Faith-based mental health education: a service-learning opportunity for nursing
      students.

PMID- 19594688
TI  - The value of microsurgery in liver research.
AB  - The use of an operating microscope in rat liver surgery makes it possible to
      obtain new experimental models and improve the already existing macrosurgical
      models. Thus, microsurgery could be a very valuable technique to improve
      experimental models of hepatic insufficiency. In the current review, we present
      the microsurgical techniques most frequently used in the rat, such as the
      portacaval shunt, the extrahepatic biliary tract resection, partial and total
      hepatectomies and heterotopic and orthotopic liver transplantation. Hence,
      reducing surgical complications allows for perfecting the resulting experimental
      models. Thus, liver atrophy related to portacaval shunt, prehepatic portal
      hypertension secondary to partial portal vein ligation, cholestasis by resection
      of the extrahepatic biliary tract, hepatic regeneration after partial
      hepatectomies, acute liver failure associated with subtotal or total hepatectomy
      and finally complications derived from preservation or rejection in orthotopic
      and heterotopic liver transplantation can be studied in more standardized
      experimental models. The results obtained are therefore more reliable and
      facilitates the flow of knowledge from the bench to the bedside. Some of these
      microsurgical techniques, because of their simplicity, can be performed by
      researchers without any prior surgical training. Other more complex microsurgical
      techniques require in-depth surgical training. These techniques are ideal for
      achieving a complete surgical training and more select microsurgical models for
      hepatology research.

PMID- 19594689
TI  - Electrical colonic stimulation reduces mean transit time in a porcine model.
AB  - Electrical stimulation is a new way to treat digestive disorders such as
      constipation. Colonic propulsive activity can be triggered by battery operated
      devices. This study aimed to demonstrate the effect of direct electrical colonic
      stimulation on mean transit time in a chronic porcine model. The impact of
      stimulation and implanted material on the colonic wall was also assessed. Three
      pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs.
      Reference colonic transit time was determined by radiopaque markers for each pig
      before implantation. It was repeated 4 weeks after implantation with sham
      stimulation and 5 weeks after implantation with electrical stimulation. Aboral
      sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for
      6 days, using an external battery operated stimulator. For each course of
      markers, a mean value was computed from transit times obtained from individual
      pig. Microscopic examination of the caecum was routinely performed after animal
      sacrifice. A reduction of mean transit time was observed after electrical
      stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P
      = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035).
      Histological examination revealed minimal chronic inflammation around the
      electrodes. Colonic transit time measured in a chronic porcine model is reduced
      by direct sequential electrical stimulation. Minimal tissue lesion is elicited by
      stimulation or implanted material. Electrical colonic stimulation could be a
      promising approach to treat specific disorders of the large bowel.

PMID- 19594690
TI  - Dehydroepiandrosterone sulphate improves cholestasis-associated fatigue in bile
      duct ligated rats.
AB  - Fatigue is a common debilitating symptom in patients with primary biliary
      cirrhosis (PBC). The mechanism of fatigue is still poorly understood. However, it
      has been reported that levels of the steroid dehydroepiandrosterone sulphate
      (DHEAS) are reduced in plasma of patients with PBC, and substitutive therapy has
      been suggested to improve fatigue symptoms experienced during the course of this
      disease. In this study, we tested the effect of DHEAS on whole body fatigue in
      rats following bile duct ligation (BDL). Fatigue was estimated by the time spent
      on an electrified grid as a result of falling off a treadmill and by performance
      of rats on an infrared beam monitor which allows the assessment of travelled
      distance and stereotypic movement activities. On day 5 after BDL surgery,
      cholestatic rats exhibited increased whole body fatigue as reflected by
      significantly increased time spent on the electrified grid, reduced travelled
      distance and reduced stereotypic movements. Administration of 5 mg kg(-1) of
      DHEAS to BDL rats for three consecutive days significantly normalized their
      behaviour. Fatigue scores were also found to be reduced in cirrhotic rats 4 weeks
      after BDL surgery, and DHEAS treatment for 3 days reduced fatigue scores at this
      stage. Dehydroepiandrosterone sulphate treatment was sufficient to increase brain
      levels of DHEAS in the BDL rats in a manner that is significantly and highly
      correlated with those of plasma DHEAS and brain dehydroepiandrosterone (DHEA).
      Substitutive therapies with DHEAS or DHEA could represent novel approaches in the
      management of fatigue due to cholestasis-induced liver failure.

PMID- 19594691
TI  - Controlling the reproductive fate of rhizobia: how universal are legume
      sanctions?
AB  - When a single host plant is infected by more than one strain of rhizobia, they
      face a tragedy of the commons. Although these rhizobia benefit collectively from
      nitrogen fixation, which increases host-plant photosynthesis, each strain might
      nonetheless increase its own reproduction, relative to competing strains, by
      diverting resources away from nitrogen fixation. Host sanctions can limit the
      evolutionary success of such rhizobial cheaters (strains that would otherwise
      benefit by fixing less nitrogen). Host sanctions have been shown in soybean
      (Glycine max) nodules, where the next generation of symbiotic rhizobia is
      descended from bacteroids (the differentiated cells that can fix nitrogen).
      Evidence for sanctions is less clear in legume species that induce rhizobial
      dimorphism inside their nodules. There, bacteroids are swollen and cannot
      reproduce regardless of how much nitrogen they fix, but sanctions could reduce
      reproduction of their undifferentiated clonemates within the same nodule. This
      rhizobial dimorphism can affect rhizobial evolution, including cheating options,
      in ways that may affect future generations of legumes. Both the importance of
      sanctions to hosts and possible physiological mechanisms for sanctions may depend
      on whether bacteroids are potentially reproductive.

PMID- 19594694
TI  - Pleiotropic effects of environment-specific adaptation in Arabidopsis thaliana.
AB  - Local adaptation may be important for the preservation of genetic diversity and
      the promotion of speciation. However, local adaptation may also constrain
      establishment in different environments. The consequences of local adaptation
      depend strongly on the pleiotropic effects of the genes involved in adaptation.
      Here, we investigated the pleiotropic effects of the genetic response to
      selection in outbred lines of Arabidopsis artificially selected to flower earlier
      under both winter- and spring-annual simulated conditions. The consequences of
      adaptation were evaluated by reciprocally transplanting selected and control
      lines between the two conditions. Selected lines always flower earlier than their
      controls, independent of growing conditions. However, selected lines, growing in
      the same condition in which they were selected, flower earlier than plants
      selected in the alternative environment. Plants selected to flower earlier in
      spring produce more fruits than controls when growing in the spring, and less
      fruits when growing in the winter; indicating that local adaptation has negative
      pleiotropic effects in another environment. Our results indicate that local
      adaptation can arise even when selection targets the same trait in the same
      direction. Furthermore, it suggests that adaptation under the two different
      environments can generate fitness trade-offs that can maintain genetic variation
      for flowering time.

PMID- 19594693
TI  - Adaptation and selection in the Senecio (Asteraceae) hybrid zone on Mount Etna,
      Sicily.
AB  - Hybrid zone theory provides a powerful theoretical framework for measuring and
      testing gene flow and selection. The Senecio aethnensis and Senecio
      chrysanthemifolius hybrid zone on Mount Etna, Sicily, was investigated to
      identify phenotypic traits under divergent selection and to assess the
      contributions of intrinsic and extrinsic selection against hybrids to hybrid zone
      maintenance. Senecio samples from 14 sites across Mount Etna were analyzed for 24
      quantitative traits classified into four groups (QTGs), six allozymes and seven
      simple sequence repeat (SSR) loci to describe patterns of variation throughout
      the hybrid zone. Narrower cline widths or shifts in cline centre position were
      observed for three QTGs relative to the molecular clines, indicating that these
      traits are likely to be under extrinsic environmental selection. Altitude was key
      to describing species distributions, but dispersal and intrinsic selection
      against hybrids explained patterns at smaller spatial scales. The hybrid zone was
      characterized by strong selection against hybrids, high dispersal rates, recent
      species contact and few loci differentiating QTGs based on indirect measures.
      These results support the hypothesis that extrinsic and intrinsic selection
      against hybrids maintains the hybrid zone and species distinctiveness despite
      gene flow between the two Senecio species on Mount Etna.

PMID- 19594695
TI  - Evolutionary pathways to self-fertilization in a tristylous plant species.
AB  - Evolutionary transitions from outcrossing to selfing occur commonly in
      heterostylous genera. The morphological polymorphisms that characterize
      heterostyly provide opportunities for different pathways for selfing to evolve.
      Here, we investigate the origins and pathways by which selfing has evolved in
      tristylous Eichhornia paniculata by providing new evidence based on morphology,
      DNA sequences and genetic analysis. The primary pathway from outcrossing to
      selfing involves the stochastic loss of the short-styled morph (S-morph) from
      trimorphic populations, followed by the spread of selfing variants of the mid
      styled morph (M-morph). However, the discovery of selfing variants of the long
      styled morph (L-morph) in Central America indicates a secondary pathway and
      distinct origin for selfing. Comparisons of multi-locus nucleotide sequences from
      27 populations sampled from throughout the geographical range suggest multiple
      transitions to selfing. Genetic analysis of selfing variants of the L- and M
      morphs demonstrates recessive control of the loss of herkogamy, although the
      number of factors appears to differ between the forms. Early stages in the
      establishment of selfing involve developmental instability in the formation of
      flowers capable of autonomous self-pollination. The relatively simple genetic
      control of herkogamy reduction and frequent colonizing episodes may often create
      demographic conditions favouring transitions to selfing in E. paniculata.

PMID- 19594696
TI  - Markers and mapping revisited: finding your gene.
AB  - This paper is an update of our earlier review (Jones et al., 1997, Markers and
      mapping: we are all geneticists now. New Phytologist 137: 165-177), which dealt
      with the genetics of mapping, in terms of recombination as the basis of the
      procedure, and covered some of the first generation of markers, including
      restriction fragment length polymorphisms (RFLPs), random amplified polymorphic
      DNA (RAPDs), simple sequence repeats (SSRs) and quantitative trait loci (QTLs).
      In the intervening decade there have been numerous developments in marker science
      with many new systems becoming available, which are herein described: cleavage
      amplification polymorphism (CAP), sequence-specific amplification polymorphism (S
      SAP), inter-simple sequence repeat (ISSR), sequence tagged site (STS), sequence
      characterized amplification region (SCAR), selective amplification of
      microsatellite polymorphic loci (SAMPL), single nucleotide polymorphism (SNP),
      expressed sequence tag (EST), sequence-related amplified polymorphism (SRAP),
      target region amplification polymorphism (TRAP), microarrays, diversity arrays
      technology (DArT), single-strand conformation polymorphism (SSCP), denaturing
      gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis
      (TGGE) and methylation-sensitive PCR. In addition there has been an explosion of
      knowledge and databases in the area of genomics and bioinformatics. The number of
      flowering plant ESTs is c. 19 million and counting, with all the opportunity that
      this provides for gene-hunting, while the survey of bioinformatics and computer
      resources points to a rapid growth point for future activities in unravelling and
      applying the burst of new information on plant genomes. A case study is presented
      on tracking down a specific gene (stay-green (SGR), a post-transcriptional
      senescence regulator) using the full suite of mapping tools and comparative
      mapping resources. We end with a brief speculation on how genome analysis may
      progress into the future of this highly dynamic arena of plant science.

PMID- 19594697
TI  - Macroevolutionary patterns of pollination accuracy: a comparison of three genera.
AB  - We hypothesize that pollination efficiency selects for equal distances between
      the pollinator reward and the anthers, and the stigmas, creating an adaptive
      ridge. We predict that this fitness surface governs the divergence of many plant
      species. We use the theory of adaptive accuracy, precision and mean optimality to
      assess how close populations lie to the hypothesized adaptive ridge and which
      factors contribute to departure from the optimum. Patterns of accuracy of pollen
      placement and receipt were compared across species in three study systems,
      Dalechampia (Euphorbiaceae), Collinsieae (Plantaginaceae) and Stylidium
      (Stylidiaceae), in order to assess the roles of stamen/stigma imprecision and
      population mean departure from the optimum in the generation of floral
      inaccuracy. We found that population mean departure from the optimum was the most
      important factor in Dalechampia, female imprecision and departure from the
      optimum were about equally important factors in Collinsieae, and stamen and
      stigma imprecision were equally important in Stylidium, with virtually no
      departure from the optimum. Possible reasons for imprecision and departure from
      the optimum were assessed using phylogenetically informed methods, indicating
      important roles of limited floral integration in the generation of imprecision,
      and conflicting selective pressures, associated with outcrossing, in the
      generation of departure from the optimum.

PMID- 19594698
TI  - Genetic changes contributing to the parallel evolution of red floral pigmentation
      among Ipomoea species.
AB  - The repeated, independent evolution of phenotypic traits reflects adaptation to
      similar selective pressures. In some circumstances, parallel phenotypic evolution
      has a common genetic basis. Here, we investigate the types of genetic change
      responsible for the repeated evolution of red flowers among Ipomoea species. We
      identified three independent transitions from cyanidin- (blue/purple) to
      pelargonidin-type (red) anthocyanin pigments among Ipomoea species. The genetic
      basis for these transitions was examined using transgenics and gene expression
      assays. Using a literature survey to estimate the expected spectrum of mutation
      types capable of producing red flowers, we evaluated whether the observed
      distribution of mutation types differed from expectation. In these species, red
      floral pigmentation appears to be caused by the disruption of flux through the
      anthocyanin pathway at the same position. Results implicate tissue-specific
      regulatory changes in the same gene, which suggests the possibility that flower
      color evolved independently via the same genetic mechanism. Although multiple
      molecular mechanisms are capable of producing red flowers, we found a deviation
      between the distributions of observed and expected mutation types responsible for
      these evolutionary transitions. Regulatory mutations thus appear to be
      preferentially targeted during evolutionary change between species. We discuss
      possible explanations for this apparent bias.

PMID- 19594699
TI  - Plant-pathogen interactions: a view from the evolutionary basement.

PMID- 19594700
TI  - The hidden language of flowering plants: floral odours as a key for understanding
      angiosperm evolution?

PMID- 19594701
TI  - Questions about floral (dis)integration.

PMID- 19594702
TI  - Gearing up for comparative genomics: analyses of the fungal class
      Dothideomycetes.

PMID- 19594703
TI  - Immunolocalization of antioxidant enzymes in high-pressure frozen root and stem
      nodules of Sesbania rostrata.
AB  - The activities and localizations of superoxide dismutases (SODs) were compared in
      root and stem nodules of the semi-aquatic legume Sesbania rostrata using gel
      activity assays and immunogold labelling, respectively. Nodules were fixed by
      high-pressure freezing and dehydrated by freeze substitution. Stem nodules showed
      more total and specific SOD activities than root nodules because of the presence
      of chloroplastic CuZnSOD. Most of the total SOD activity of stem and root nodules
      resulted from 'cytosolic' CuZnSOD, localized in the cytoplasm and chromatin, and
      from MnSOD in the bacteroids and in the mitochondria of vascular tissue. FeSOD
      was present in nodule plastids and in leaf chloroplasts, and was found to be
      associated with chromatin. Superoxide production was detected histochemically in
      the vascular bundles and in the infected tissue of stem and root nodules, whereas
      peroxide accumulation was observed in the cortical cell walls and intercellular
      spaces, as well as within the infection threads of both nodule types. These data
      suggest a role of CuZnSOD and FeSOD in protecting nuclear DNA from reactive
      oxygen species and/or in modulating gene activity. The enhanced levels of
      CuZnSOD, MnSOD and superoxide production in vascular bundle cells are consistent
      with a role of CuZnSOD and superoxide in the lignification of xylem vessels, but
      also suggest additional functions in coping with superoxide production by the
      high respiratory activity of parenchyma cells.

PMID- 19594704
TI  - The olfactory component of floral display in Asimina and Deeringothamnus
      (Annonaceae).
AB  - Floral scent is a key component of floral display, and probably one of the first
      floral attractants linking insect pollinators to the radiation of Angiosperms. In
      this article, we investigate floral scent in two extra-tropical genera of
      Annonaceae. We discuss floral scent in the context of differing pollination
      strategies in these genera, and compare their scent to that of a close tropical
      relative. Floral volatiles were collected for Annona glabra, Asimina and
      Deeringothamnus whole flowers and dissected floral organs, using a standardized
      static-headspace solid phase microextraction method. Scents were analyzed using
      gas chromatography-mass spectrometry, and identified using known standards. The
      floral scents of these species are highly dynamic, varying between floral organs,
      sexual stages and species. Maroon-flowered species of Asimina produce 'yeasty'
      odors, dominated by fermentation volatiles and occasionally containing sulfurous
      or nitrogenous compounds. White-flowered species of Asimina and Deeringothamnus
      produce pleasant odors characterized by lilac compounds, benzenoids and
      hydrocarbons. Annona glabra produces a strong, fruity-acetonic scent dominated by
      3-pentanyl acetate and 1,8-cineole. The fermented/decaying scents of maroon
      flowered species of Asimina suggest mimicry-based pollination strategies similar
      to aroids and stapeliads, whereas the pleasant scents of white-flowered species
      of Asimina suggest honest, reward-based pollination strategies. The scent of
      Annona glabra is typical of specialized beetle pollination systems common to
      tropical Annonaceae.

PMID- 19594707
TI  - Molecular components required for the targeting of PEX7 to peroxisomes in
      Arabidopsis thaliana.
AB  - PEX7 is a soluble import receptor that recognizes peroxisomal targeting signal
      type 2 (PTS2)-containing proteins. In the present study, using a green
      fluorescent protein (GFP) fusion protein of PEX7 (GFP-PEX7), we analyzed the
      molecular function and subcellular localization of PEX7 in Arabidopsis thaliana.
      The overexpression of GFP-PEX7 resulted in defective glyoxysomal fatty acid beta
      oxidation, but had no significant effect on leaf peroxisomal function. Analysis
      of the subcellular localization of GFP-PEX7 in transgenic Arabidopsis showed that
      GFP-PEX7 localizes primarily to the peroxisome. Transient expression of a C- or N
      terminal fusion protein of PEX7 and yellow fluorescent protein (YFP) (PEX7-YFP
      and YFP-PEX7, respectively) in leek epidermal cells, using the particle
      bombardment technique, confirmed that fluorescent protein-tagged PEX7 localizes
      to peroxisomes in Arabidopsis. Immunoblot analysis revealed that GFP-PEX7
      accumulates primarily in peroxisomal membrane fractions, whereas endogenous PEX7
      was distributed evenly in cytosolic and peroxisomal membrane fractions, which
      indicated that both endogenous PEX7 and GFP-PEX7 are properly targeted to
      peroxisomal membranes. The results of bimolecular fluorescence complementation
      (BiFC) and yeast two-hybrid analyses showed that PEX7 binds directly to PTS2
      containing proteins and PEX12 in the peroxisomal membrane. We used red
      fluorescent protein (tdTomato) fusion protein of PEX7 (tdTomato-PEX7) in several
      Arabidopsis pex mutants to identify proteins required for the targeting of PEX7
      to peroxisomes in planta. The results demonstrated that pex14, pex13 and pex12
      mutations disrupt the proper targeting of PEX7 to peroxisomes. Overall, our
      results suggest that the targeting of PEX7 to peroxisomes requires four proteins:
      a PTS2-containing protein, PEX14, PEX13 and PEX12.

PMID- 19594708
TI  - Cutin deficiency in the tomato fruit cuticle consistently affects resistance to
      microbial infection and biomechanical properties, but not transpirational water
      loss.
AB  - Plant cuticles are broadly composed of two major components: polymeric cutin and
      a mixture of waxes, which infiltrate the cutin matrix and also accumulate on the
      surface, forming an epicuticular layer. Although cuticles are thought to play a
      number of important physiological roles, with the most important being to
      restrict water loss from aerial plant organs, the relative contributions of cutin
      and waxes to cuticle function are still not well understood. Tomato (Solanum
      lycopersicum) fruits provide an attractive experimental system to address this
      question as, unlike other model plants such as Arabidopsis, they have a
      relatively thick astomatous cuticle, providing a poreless uniform material that
      is easy to isolate and handle. We identified three tomato mutants, cutin
      deficient 1 (cd1), cd2 and cd3, the fruit cuticles of which have a dramatic (95
      98%) reduction in cutin content and substantially altered, but distinctly
      different, architectures. This cutin deficiency resulted in an increase in
      cuticle surface stiffness, and in the proportions of both hydrophilic and
      multiply bonded polymeric constituents. Furthermore, our data suggested that
      there is no correlation between the amount of cutin and the permeability of the
      cuticle to water, but that cutin plays an important role in protecting tissues
      from microbial infection. The three cd mutations were mapped to different loci,
      and the cloning of CD2 revealed it to encode a homeodomain protein, which we
      propose acts as a key regulator of cutin biosynthesis in tomato fruit.

PMID- 19594709
TI  - Extracellular ATP is a regulator of pathogen defence in plants.
AB  - In healthy plants extracellular ATP (eATP) regulates the balance between cell
      viability and death. Here we show an unexpected critical regulatory role of eATP
      in disease resistance and defensive signalling. In tobacco, enzymatic depletion
      of eATP or competition with non-hydrolysable ATP analogues induced pathogenesis
      related (PR) gene expression and enhanced resistance to tobacco mosaic virus and
      Pseudomonas syringae pv. tabaci. Artificially increasing eATP concentrations
      triggered a drop in levels of the important defensive signal chemical salicylic
      acid (SA) and compromised basal resistance to viral and bacterial infection.
      Inoculating tobacco leaf tissues with bacterial pathogens capable of activating
      PR gene expression triggered a rapid decline in eATP. Conversely, inoculations
      with mutant bacteria unable to induce defence gene expression failed to deplete
      eATP. Furthermore, a collapse in eATP concentration immediately preceded PR gene
      induction by SA. Our study reveals a previously unsuspected role for eATP as a
      negative regulator of defensive signal transduction and demonstrates its
      importance as a key signal integrating defence and cell viability in plants.

PMID- 19594710
TI  - An AP2-type transcription factor, WRINKLED1, of Arabidopsis thaliana binds to the
      AW-box sequence conserved among proximal upstream regions of genes involved in
      fatty acid synthesis.
AB  - Although an APETALA2 (AP2)-type transcription factor, WRINKLED1 (WRI1), has been
      shown to be required for accumulation of triacylglycerols (TAGs) in Arabidopsis
      seeds, its direct target genes have not been established. Overexpression of WRI1
      up-regulated a set of genes involved in fatty acid (FA) synthesis in plastids,
      including genes for a subunit of pyruvate kinase (Pl-PKbeta1), acetyl-CoA
      carboxylase (BCCP2), acyl carrier protein (ACP1), and ketoacyl-acyl carrier
      protein synthase (KAS1), while expression of these genes is reduced in mutants
      with reduced WRI1 expression. Transient expression of LUC reporter genes with the
      proximal sequences upstream from the ATG codon of Pl-PKbeta1, BCCP2, and KAS1 in
      protoplasts was activated by co-expression of WRI1, and recombinant WRI1 bound to
      these upstream sequences in vitro. The seven WRI1 binding sites shared a sequence
      [CnTnG](n)(7)[CG], where n is any nucleotide designated as the AW-box, and
      mutations in AW-boxes near the transcription start site and in the 5'
      untranslated region of Pl-PKbeta1 abolished activation by WRI1 in protoplasts and
      expression during seed maturation. Although expression of genes for the synthesis
      of TAGs and packaging into oil bodies in the endoplasmic reticulum in developing
      seeds required WRI1, their expression was not up-regulated by WRI1
      overexpression. Thus, WRI1 promotes the flow of carbon to oil during seed
      maturation by directly activating genes involved in FA synthesis and controlling
      genes for assembly and storage of TAG.

PMID- 19594711
TI  - Phytoene synthase activity controls the biosynthesis of carotenoids and the
      supply of their metabolic precursors in dark-grown Arabidopsis seedlings.
AB  - Carotenoids are plastidial isoprenoids essential for plant life. In Arabidopsis
      thaliana carotenoid biosynthesis is strongly upregulated when seedlings that
      germinate in the dark (etiolated) emerge from the soil and light derepresses
      photomorphogenesis, causing etioplasts to become chloroplasts. We found that
      carotenoid biosynthesis is also induced when deetiolation is derepressed in the
      absence of actual light, eventually resulting in improved greening (chlorophyll
      accumulation) upon illumination. The increased production of carotenoids in the
      dark correlates with an upregulated activity of phytoene synthase (PSY; the first
      committed enzyme of carotenogenesis) and the induction of PSY gene expression in
      cotyledons (where carotenoids accumulate in dark-grown seedlings). The metabolic
      precursors for carotenoid synthesis under these conditions are mostly supplied by
      the plastidial methylerythritol 4-phosphate (MEP) pathway. Accumulation of flux
      controlling MEP pathway enzymes, such as deoxyxylulose 5-phosphate synthase
      (DXS), is post-transcriptionally increased when deetiolation is derepressed in
      the dark. Unlike the situation observed in light-grown plants, however, the sole
      overexpression of DXS in dark-grown seedlings does not increase carotenoid
      accumulation. By contrast, induced expression of a PSY-encoding transgene results
      in increased carotenoid levels and a concomitant post-transcriptional
      accumulation of DXS. These data provide evidence for a feedback mechanism by
      which PSY controls metabolic flux to the carotenoid pathway in plants.

PMID- 19594712
TI  - Letter from the editor.

PMID- 19594713
TI  - Creating a common language for building a successful talent management program:
      paving the path for succession, and success, within your organization.

PMID- 19594714
TI  - Is your blood center a private foundation?

PMID- 19594715
TI  - The case of the overworked technical director.

PMID- 19594716
TI  - Best practices for requesting IT improvements.

PMID- 19594717
TI  - A conversation with David Perez, president and CEO of CaridianBCT.

PMID- 19594718
TI  - Hospital billing for blood processing and transfusion for inpatient stays.
AB  - Medicare, an important payer for hospitals, reimburses hospitals for inpatient
      stays using Diagnosis Related Groups (DRGs). Many private insurers also use the
      DRG methodology to reimburse hospitals for their services. Therefore, those blood
      service organizations that bill Medicare directly require an understanding of the
      DRG system of payment to enable them to bill Medicare correctly, and in order to
      be certain they are adequately reimbursed. Blood centers that do not bill
      Medicare directly need to understand how hospitals are reimbursed for blood and
      blood components as this affects a hospital's ability to pay service fees related
      to these products. This review presents a detailed explanation of how hospitals
      are reimbursed by the Centers for Medicare and Medicaid Services (CMS) for
      Medicare inpatient services, including blood services.

PMID- 19594719
TI  - Source plasma: future outlook.

PMID- 19594723
TI  - Defending the duty to research?
AB  - In 2005, John Harris published a paper in the Journal of Medical Ethics in which
      he claimed that there was a duty to support scientific research. With Sarah Chan,
      he defended his claims against criticisms in this journal in 2008. In this paper
      I examine the defence, and claim that it is not powerful. Although he has
      established a slightly stronger position, it is not clear that the defence is
      sufficiently strong to show that there is a duty to support scientific research.
      Important questions about fairness, about rescue, and about the relationship
      between reasons and obligations to act can still be raised; and these questions
      are important enough to destabilize the defence.

PMID- 19594724
TI  - A precautionary principle for dual use research in the life sciences.
AB  - Most life science research entails dual-use complexity and may be misused for
      harmful purposes, e.g. biological weapons. The Precautionary Principle applies to
      special problems characterized by complexity in the relationship between human
      activities and their consequences. This article examines whether the principle,
      so far mainly used in environmental and public health issues, is applicable and
      suitable to the field of dual-use life science research. Four central elements of
      the principle are examined: threat, uncertainty, prescription and action.
      Although charges against the principle exist - for example that it stifles
      scientific development, lacks practical applicability and is poorly defined and
      vague - the analysis concludes that a Precautionary Principle is applicable to
      the field. Certain factors such as credibility of the threat, availability of
      information, clear prescriptive demands on responsibility and directives on how
      to act, determine the suitability and success of a Precautionary Principle.
      Moreover, policy-makers and researchers share a responsibility for providing and
      seeking information about potential sources of harm. A central conclusion is that
      the principle is meaningful and useful if applied as a context-dependent moral
      principle and allowed flexibility in its practical use. The principle may then
      inspire awareness-raising and the establishment of practical routines which
      appropriately reflect the fact that life science research may be misused for
      harmful purposes.

PMID- 19594725
TI  - Post-abortion syndrome: creating an affliction.
AB  - The contention that abortion harms women constitutes a new strategy employed by
      the pro-life movement to supplement arguments about fetal rights. David C.
      Reardon is a prominent promoter of this strategy. Post-abortion syndrome purports
      to establish that abortion psychologically harms women and, indeed, can harm
      persons associated with women who have abortions. Thus, harms that abortion is
      alleged to produce are multiplied. Claims of repression are employed to
      complicate efforts to disprove the existence of psychological harm and causal
      antecedents of trauma are only selectively investigated. We argue that there is
      no such thing as post-abortion syndrome and that the psychological harms Reardon
      and others claim abortion inflicts on women can usually be ascribed to different
      causes. We question the evidence accumulated by Reardon and his analysis of data
      accumulated by others. Most importantly, we question whether the conclusions
      Reardon has drawn follow from the evidence he cites.

PMID- 19594726
TI  - Moral fictions and medical ethics.
AB  - Conventional medical ethics and the law draw a bright line distinguishing the
      permitted practice of withdrawing life-sustaining treatment from the forbidden
      practice of active euthanasia by means of a lethal injection. When clinicians
      justifiably withdraw life-sustaining treatment, they allow patients to die but do
      not cause, intend, or have moral responsibility for, the patient's death. In
      contrast, physicians unjustifiably kill patients whenever they intentionally
      administer a lethal dose of medication. We argue that the differential moral
      assessment of these two practices is based on a series of moral fictions -
      motivated false beliefs that erroneously characterize withdrawing life-sustaining
      treatment in order to bring accepted end-of-life practices in line with the
      prevailing moral norm that doctors must never kill patients. When these moral
      fictions are exposed, it becomes apparent that conventional medical ethics
      relating to end-of-life decisions is radically mistaken.

PMID- 19594727
TI  - Human dignity in international policy documents: a useful criterion for public
      policy?
AB  - Current developments in biomedicine are presenting us with difficult ethical
      decisions and raising complex policy questions about how to regulate these new
      developments. Particularly vexing for governments have been issues related to
      human embryo experimentation. Because some of the most promising biomedical
      developments, such as stem cell research and nuclear somatic transfer, involve
      such experimentation, several international bodies have drafted documents aimed
      to provide guidance to governments when developing biomedical science policy.
      Here I focus on two such documents: the Council of Europe's Convention for the
      Protection of Human Rights and Dignity of the Human Being and the Additional
      Protocol to the Convention for the Protection of Human Rights and Dignity of the
      Human Being. I argue that by using human dignity as a criterion to determine the
      permissibility of particular human embryo research practices, these documents
      cannot aid in identifying research that would be contrary to human dignity. Thus,
      they fail to guide public policy on embryo experimentation. Their use of human
      dignity as a criterion makes their task of offering guidance unfeasible because
      the concept as used in these documents is too vague and is applied in
      contradictory ways. I discuss the main goals of these documents and their claims
      in relation to human embryo research. I then discuss how they have influenced
      public policy in several countries. Finally, I show that although these Council
      of Europe treaties attempt to serve as public policy guides in the area of embryo
      research, they fail to do so.

PMID- 19594728
TI  - Post-trial access to antiretrovirals: who owes what to whom?
AB  - Many recent articles argue that participants who seroconvert during HIV
      prevention trials deserve treatment when they develop AIDS, and there is a
      general consensus that the participants in HIV/AIDS treatment trials should have
      continuing post-trial access. As a result, the primary concern of many ethicists
      and activists has shifted from justifying an obligation to treat trial
      participants, to working out mechanisms through which treatment could be
      provided. In this paper I argue that this shift frequently conceals an important
      assumption: that if there is an obligation to supply treatment, then any party
      who could provide it may be prevailed upon to discharge the obligation. This
      assumption is false. The reasons why trial participants should get ART affect who
      has the duty to provide it. We should not burden governments with the obligations
      of sponsors, nor researchers with the obligations of the international community.
      And we should not deprive a group of treatment because their need is less salient
      than that of research participants. Insisting otherwise may lead to people being
      wrongfully deprived of access to antiretrovirals.

PMID- 19594729
TI  - Mercury exposure increases circulating net matrix metalloproteinase (MMP)-2 and
      MMP-9 activities.
AB  - Mercury (Hg) exposure causes health problems that may result from increased
      oxidative stress and matrix metalloproteinase (MMP) levels. We investigated
      whether there is an association between the circulating levels of MMP-2, MMP-9,
      their endogenous inhibitors (the tissue inhibitors of metalloproteinases; TIMPs)
      and the circulating Hg levels in 159 subjects environmentally exposed to Hg.
      Blood and plasma Hg were determined by inductively coupled plasma-mass
      spectrometry (ICP-MS). MMP and TIMP concentrations were measured in plasma
      samples by gelatin zymography and ELISA respectively. Thiobarbituric acid
      reactive species (TBARS) were measured in plasma to assess oxidative stress.
      Selenium (Se) levels were determined by ICP-MS because it is an antioxidant. The
      relations between bioindicators of Hg and the metalloproteinases levels were
      examined using multivariate regression models. While we found no relation between
      blood or plasma Hg and MMP-9, plasma Hg levels were negatively associated with
      TIMP-1 and TIMP-2 levels, and thereby with increasing MMP-9/TIMP-1 and MMP-2/TIMP
      2 ratios, thus indicating a positive association between plasma Hg and
      circulating net MMP-9 and MMP-2 activities. These findings provide a new insight
      into the possible biological mechanisms of Hg toxicity, particularly in
      cardiovascular diseases.

PMID- 19594730
TI  - Progression of lipid peroxidation measured as thiobarbituric acid reactive
      substances, damage to DNA and histopathological changes in the liver of rats
      subjected to a methionine-choline-deficient diet.
AB  - Methionine-choline-deficient diet represents a model for the study of the
      pathogenesis of steatohepatitis. Male rats were divided into three groups, the
      first group receiving a control diet and the other two groups receiving a
      methionine-choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2),
      respectively. The livers of the animals were collected for the determination of
      vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration,
      DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH
      content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1
      and MCD2) compared to control diet, and hepatic vitamin E concentration differed
      (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a
      lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2
      group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA
      injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes).
      Liver histopathological evaluation showed that steatosis, present in experimental
      groups was micro- and macro-vesicular and concentrated around the centrolobular
      vein, zone 3, with preservation of the portal space. The inflammatory infiltrate
      was predominantly periductal and the steatosis and inflammatory infiltrate was
      similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was
      greater in the MCD2 group. The study describes the contribution of a methionine
      choline-deficient diet to the progression of steatosis, lipid peroxidation and
      hepatic DNA damage in rats, serving as a point of reflection about the role of
      these nutrients in the western diet and the elevated non-alcoholic
      steatohepatitis rates in humans.

PMID- 19594731
TI  - Disease insight and treatment perception of men on active surveillance for early
      prostate cancer.
AB  - STUDY TYPE: Survey (prospective cohort). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To
      investigate the levels of knowledge of prostate cancer and the perception of
      active surveillance (AS) in men on AS, as AS for early prostate cancer instead of
      radical treatment might partly solve the over-treatment dilemma in this disease,
      but might be experienced as a complex and contradictory strategy by patients.
      PATIENTS AND METHODS: In all, 150 Dutch men recently diagnosed with early
      prostate cancer participating in a prospective protocol-based AS programme (PRIAS
      study) received questionnaires, including a 15-item measure on their general
      knowledge of prostate cancer, and open-ended questions on the most important
      disadvantages and advantages of AS, and on the specific perception of AS. We
      assessed knowledge scores and explored potentially associated factors, the stated
      (dis)advantages and specific perceptions. RESULTS: The questionnaire response
      rate was 86% (129/150). Participants provided correct answers to a median
      (interquartile range) of 13 (12-14) of 15 (87%) knowledge items. Younger and
      higher educated men had higher knowledge scores. In line with a priori
      hypotheses, the most frequently reported advantage and disadvantage of AS were
      the delay of side-effects and the risk of disease progression, respectively.
      Specific negative experiences included the feeling of losing control over
      treatment decisions, distress at follow-up visits, and the desire for a more
      active participation in disease management. No conceptually wrong understandings
      or expectations of AS were identified. CONCLUSIONS: We found adequate knowledge
      of prostate cancer levels and realistic perceptions of the AS strategy in
      patients with early prostate cancer and on AS. These findings suggest adequate
      counselling by the physician or patient self-education.

PMID- 19594732
TI  - Circumcision is not mandatory in penile surgery.
AB  - OBJECTIVE: To assess the outcome of not circumcising patients having surgery to
      correct a congenital or acquired curvature, through a subcoronal approach.
      PATIENTS AND METHODS: In a series of 251 consecutive patients (mean age 46 years,
      range 17-74) that had their penis straightened by either a Lue (86), or a Nesbit
      procedure (162) or a combination of both (three) between 2000 and 2008, a
      subcoronal circumferential incision was used for the degloving in 241. Among the
      183 patients who had not been previously circumcised, 22 presented with a tight
      foreskin and were offered a circumcision; six of them refused to be circumcised.
      Of the remaining 161 patients, 115, including two who had previous penile
      surgery, opted not to be circumcised. RESULTS: After a median (range) follow-up
      of 5.5 (1-50) months, secondary circumcision was performed in three of the six
      patients with a tight foreskin, in one of the 113 (0.8%) with a normal
      retractable foreskin and in one of the two who had had previous penile surgery
      and had a normal foreskin. CONCLUSIONS: Circumcision should not be considered as
      a routine part of penile surgery unless a significant phimosis is present or
      revisional surgery is contemplated.

PMID- 19594734
TI  - Healthcare costs associated with prostate cancer: estimates from a population
      based study.
AB  - STUDY TYPE: Health Economic (multiway sensitivity analyses). LEVEL OF EVIDENCE:
      2b. OBJECTIVE: To estimate the total healthcare costs and costs attributable to
      prostate cancer across all stages of disease, and to determine the predictors of
      those costs, as describing the cost of care for patients with prostate cancer is
      useful to understand the economic burden of illness, explore patterns of care,
      and provide reliable cost data for economic evaluations. METHODS: We estimated
      direct medical costs for 42 484 men diagnosed with prostate cancer in Ontario,
      Canada between 1995 and 2002 using linked administrative data. The observation
      time was divided into five phases: (I) before diagnosis (6 months before); (II)
      initial care (12 months after diagnosis); (III) continuing care; (IV) pre
      terminal care (from 18 to 6 months before death); and (V) terminal care (6 months
      before death). Attributable costs were estimated by comparing costs in cases to
      matched controls. RESULTS: The total direct costs per 100 days (in $Canadian,
      2004) were: Phase I $1297; II $3289; III $1495; IV $5629; and V $16 020. Prostate
      cancer-attributable costs accounted for 72% of total costs in the 12-month period
      after diagnosis (II, $2366), but <35% of total costs in phases III to V ($398,
      $1977 and $3140, respectively). An advanced stage at diagnosis, being older at
      diagnosis, and higher comorbidity were associated with increased costs.
      CONCLUSION: Prostate cancer is associated with increased direct healthcare costs
      over the natural history of the disease. Costs are highest around two events,
      cancer diagnosis and cancer death. Future research should evaluate costs borne by
      private insurers and patients, evaluate the effects of patient and system
      variables on lifetime costs, and explore differences in end-of-life healthcare
      costs across countries.

PMID- 19594733
TI  - Effects of combined valproic acid and the epidermal growth factor/vascular
      endothelial growth factor receptor tyrosine kinase inhibitor AEE788 on renal cell
      carcinoma cell lines in vitro.
AB  - OBJECTIVE: To evaluate adhesion and growth inhibiting effects of the multiple
      receptor tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)
      inhibitor valproic acid (VPA) on renal cell carcinoma (RCC) cells. MATERIALS AND
      METHODS: Caki-1 cells were treated with AEE788 and VPA, either alone or in
      combination, to investigate RCC cell adhesion to vascular endothelial cells or to
      immobilized extracellular matrix proteins. Tumour cell proliferation was examined
      by MTT dye reduction assay. Effects of drug treatment on cell signalling pathways
      were determined by Western blotting. The expression levels of integrin alpha and
      beta subtypes were evaluated by flow cytometry (surface expression) and Western
      blotting (intracellular protein expression). RESULTS: RCC cell treatment with
      AEE788 and VPA in combination resulted in a stronger inhibition of tumour cell
      proliferation than that caused by either drug alone. There were also additive
      effects of the combined treatment on tumour cell adhesion to endothelial cells
      and to immobilized laminin (but not to immobilized fibronectin and collagen).
      AEE788 alone or combined with VPA reduced Akt expression and histone H3
      acetylation. Both compounds altered integrin alpha and beta subtype expression,
      in particular alpha1, alpha3 and beta4, and blocked integrin-dependent integrin
      linked kinase and focal-adhesion kinase (total and phosphorylated) signalling.
      CONCLUSIONS: Both AEE788 and VPA profoundly block the interaction of RCC cells
      with endothelium and extracellular matrix and reduce tumour growth in vitro.
      Therefore, this combined regimen warrants further preclinical and possible
      clinical study for treating advanced RCC.

PMID- 19594735
TI  - Evidence-based urology in practice: the Cochrane Library.

PMID- 19594736
TI  - Evaluation of semen variables, sperm chromosomal abnormalities and reproductive
      endocrine profile in patients with chronic hepatitis C.
AB  - OBJECTIVE: To evaluate reproductive endocrine profile, sperm chromosomal
      abnormalities, and semen quality in patients with chronic hepatitis C. PATIENTS,
      SUBJECTS AND METHODS: In all, 82 patients with chronic hepatitis C, aged 18-60
      years, were recruited for the study; 76 age-matched healthy male volunteers
      served as controls. All participants provided a medical history and had a
      complete physical examination and routine semen analysis. Two blood samples were
      drawn from each participant at 15-min intervals to determine the resting levels
      of luteinizing-hormone (LH), follicle-stimulating hormone (FSH), prolactin,
      testosterone, oestradiol, and sex hormone-binding globulin. The hypothalamus
      pituitary-testis axis was assessed using the gonadotrophin-releasing hormone
      (GnRH) test. All participants also received an injection of human chorionic
      gonadotrophin (hCG) and serum testosterone was determined before the hCG
      injection and on the third day afterwards. Conventional karyotype analysis and
      triple-colour fluorescence in situ hybridization for chromosomes X, Y and 18 were
      conducted in all patients and controls. RESULTS: The mean basal serum levels for
      LH, FSH, and testosterone in patients with hepatitis C was significantly lower
      than the mean for normal controls (P = 0.01). The injection of GnRH analogue did
      not yield significantly higher FSH and LH levels in the patients than in normal
      controls (P = 0.001). In patients with chronic hepatitis C, the mean total sperm
      count, motility and normal morphology was significantly lower than in controls (P
      = 0.001). There was a significantly greater frequency of disomy in men with
      chronic hepatitis C than controls for chromosomes 18, X, and Y (P = 0.01).
      CONCLUSIONS: Patients with chronic hepatitis C are at risk of showing sperm
      chromosomal abnormalities, the incidence of which is higher in patients with more
      advanced disease. Hypogonadotrophic hypogonadism is caused by the selective loss
      of pituitary gonadotrophin function. Further studies are needed to replicate our
      results.

PMID- 19594737
TI  - Natural history of benign prostatic enlargement: long-term longitudinal
      population-based study of prostate volume doubling times.
AB  - OBJECTIVES: To measure prostate volume doubling times (PVDTs) for a large sample
      of community men followed serially by transrectal ultrasonography (TRUS), and to
      determine whether specific characteristics are associated with a rapid PVDT.
      SUBJECTS AND METHODS: A subsample of 446 subjects from a larger cohort of
      American white men aged 40-79 years were evaluated biennially for a median
      (range) follow-up of 10 (3-14) years. Mixed-effects regression models were used
      to estimate prostate growth rates and PVDT for subjects with three or more or
      with five or more serial biennial TRUS PV measurements. RESULTS: The median (25
      75th percentile) PVDT was 32.6 (24.6-44.0) years. The average annual increase in
      PV was 2.2%. The PVDT distribution was constant in men of all age groups studied
      (r < 0.001, P = 0.99). The factor most strongly associated with PVDT was baseline
      transition zone volume (r = -0.55, P < 0.001). Baseline total prostate-specific
      antigen (PSA) level, free PSA and total PV were also significantly inversely
      associated with PVDT (r = -0.30, -0.44 and -0.32, respectively, all P < 0.001).
      Age, baseline anthropomorphic measurements, hormone levels and specific lifestyle
      characteristics were not significantly correlated with PVDT. CONCLUSION: These
      data indicate that PVDT might be a useful future measure of benign prostatic
      growth. They provide a basis to forecast PV at 10, 20, or 30 years later, after
      one baseline TRUS measurement of prostate volume, and can be presented in a
      simple nomogram.

PMID- 19594738
TI  - Living-donor renal transplantation of grafts with incidental renal masses after
      ex-vivo partial nephrectomy.
AB  - OBJECTIVES: To assess transplantation of high-risk kidneys with incidental renal
      masses (found occasionally during the routine evaluation of a living kidney
      donor) into recipients with limited life-expectancy on haemodialysis, as this
      offers a potential solution to the current organ deficit. PATIENTS AND METHODS:
      We detected five small (<2.3 cm), incidental, enhancing renal masses during donor
      evaluation. All patients had a standard metastatic evaluation. After laparoscopic
      donor nephrectomy a back-table partial nephrectomy was performed and frozen
      section analysis was used to confirm both the diagnosis and negative surgical
      margins before transplantation. RESULTS: Renal cell carcinoma was found in three
      of the five masses (one each cystic, clear cell and papillary; Fuhrman grades II,
      II and III, respectively) and the other two patients had angiomyolipoma. There
      were no long-term complications in the transplanted kidneys. One patient
      developed delayed acute humoral rejection after transplantation and was treated
      appropriately. Both donor and recipient were followed with periodic imaging. At a
      median (range) last follow-up of 15 (1-41) months, four patients were alive and
      one had died from complications after a fall. The cancer-specific survival was
      100%. There was no evidence of local recurrence in any patient at the last follow
      up. CONCLUSION: Live donor kidneys with incidental small renal masses might be
      acceptable for transplantation in high-risk recipients after careful back-table
      partial nephrectomy.

PMID- 19594739
TI  - Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for
      reducing bladder hyperactivity.
AB  - OBJECTIVE: To investigate the efficacy of intravesical liposomes against dimethyl
      sulphoxide (DMSO), and pentosan polysulphate (PPS) in reducing chemically induced
      bladder hyperactivity in rats. MATERIALS AND METHODS: Bladder reflex activity of
      female Sprague-Dawley rats was evaluated by continuous cystometry under urethane
      anaesthesia (1.0 g/kg). After obtaining a control cystometrogram (CMG) with
      normal saline (0.04 mL/min) for 2 h, bladder hyperactivity was then induced by 1
      h infusion of protamine sulphate (10 mg/mL) followed by a 1-h infusion of KCl
      (500 mm). Six rats each were then infused with KCl-based preparations containing
      either 50% DMSO, PPS (6 mg/mL), or liposomes (2 mg/mL) for 2 h. The variables
      measured included the intercontraction interval (ICI), pressure threshold (PT)
      and baseline pressure (BP). RESULTS: Sequential infusion of protamine
      sulphate/KCl induced hyperactive bladder with no significant difference in ICI,
      PT or BP among groups before initiating treatment. ICI was significantly
      increased after infusion of PPS (58.1% increase) and liposomes (156.8% increase)
      but there was no increase with DMSO. PT was not significantly affected by
      liposome infusion but slightly increased with PPS (12.4% increase). There was a
      large and significant increase in PT and BP with DMSO (116.5% increase) and BP
      largely remained unchanged after instillation with liposomes or PPS. CONCLUSIONS:
      Intravesical liposomes and PPS have a beneficial effect in a bladder
      hyperactivity rat model, while acute instillation of DMSO does not. Intravesical
      liposomes were effective in doubling the ICI compared with PPS, and might be a
      new treatment option for bladder hyperactivity.

PMID- 19594740
TI  - The role of lymphangiogenesis in lymphatic tumour spread of urological cancers.
AB  - Metastases to regional lymph nodes are a common early event in many malignant
      diseases and have a poor prognosis, including in urological cancers. Molecular
      pathways contributing to lymphatic tumour dissemination and lymph node metastasis
      remain poorly understood. Besides the process of lymphovascular invasion (LVI),
      recent studies suggested de novo lymphatic vessel formation (i.e.
      lymphangiogenesis) as a potential mechanism of lymphatic tumour spread. Specific
      markers for lymphatic endothelium have recently been discovered, enabling basic
      morphological studies on lymphatic vessel density. There is a gap in the
      knowledge of the functional relationship between tumoral lymphatic vessels, LVI,
      lymphangiogenesis and the formation of lymph node metastases. The identification
      of lymph-specific growth factors (e.g. vascular endothelial growth factor-C and 
      D) as promoters of lymphatic metastasis has resulted in the interesting idea of
      targeting the pathways involved in lymphatic tumour progression. We summarize
      preliminary evidence on the role of lymphangiogenesis during the formation of
      lymphatic metastasis in the most common urological cancers.

PMID- 19594741
TI  - Long-term follow-up of 3-month neoadjuvant hormone therapy before radical
      prostatectomy in a randomized trial.
AB  - OBJECTIVE: To report our long-term follow-up of an institutional randomized
      prospective trial of radical prostatectomy (RP) with or without a 3-month course
      of neoadjuvant hormone therapy (NHT), which results in pathological downstaging,
      but generally no reduction in biochemical recurrence (BCR) on early follow-up (at
      3 years). PATIENTS AND METHODS: From December 1992 to June 1996, 148 patients
      with clinically localized prostate cancer were randomized to RP only or 3 months
      of goserelin acetate and flutamide before RP. BCR was defined as a detectable
      serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after
      surgery, with a confirmatory increase. RESULTS: The median follow-up for BCR-free
      patients was 8 years. There was no significant difference in BCR-free
      probabilities between groups (P = 0.7). The BCR-free probability at 7 years was
      78% for patients undergoing RP only and 80% for patients undergoing NHT and RP
      (difference of 2%; 95% confidence interval, CI, 12-16%). A Cox regression showed
      no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56
      2.39, P = 0.7). Overall, two patients had local recurrence and six developed
      metastases, and were evenly distributed among the RP only and NHT groups.
      CONCLUSION: Although our study was not originally powered to detect differences
      in BCR, there was no overall benefit in BCR-free probability, local recurrence or
      metastasis with 3 months of NHT at 8 years of follow-up. Pending evidence of
      improvement in patient outcomes, NHT before RP appears to be unjustified outside
      of clinical trials.

PMID- 19594742
TI  - Increased erythropoiesis of beta-thalassaemia/Hb E proerythroblasts is mediated
      by high basal levels of ERK1/2 activation.
AB  - Beta-thalassaemia is one of the most common inherited anaemias, arising from a
      partial or complete loss of beta-globin chain synthesis. In severe cases, marked
      bone marrow erythroid hyperplasia, believed to result from erythropoietin (EPO)
      mediated feedback from the anaemic condition is common, however, as yet, no study
      has investigated EPO-mediated signal transduction in thalassaemic erythroid
      cells. Using proerythroblasts generated from peripheral blood circulating CD34+
      haematopoietic progenitor cells, the activation of the mitogen-activated protein
      kinase/extracellular signal-regulated kinases (MAPK/ERKs) pathway was examined
      under conditions of steady state growth, cytokine deprivation and post-EPO
      stimulation. Levels of cellular cyclic adenosine monophosphate (cAMP) and Ca2+
      were determined as was the degree of erythroid expansion. A significantly higher
      basal level of phosphorylation of ERK1/2 was observed in beta-thalassaemia/Hb E
      proerythroblasts as compared to normal controls, which was coupled with
      significantly higher levels of both cAMP and Ca2+. Modulation of either cAMP or
      Ca2+ or direct inhibition of MAPK/ERK kinase (MEK) reduced basal levels of ERK1/2
      phosphorylation, as well as significantly reducing the level of erythroid
      expansion. These results suggest that, in contrast to current models, hyper
      proliferation of beta-thalassaemia/Hb E proerythroblasts is an intrinsic process
      driven by higher basal levels of ERK1/2 phosphorylation resulting from
      deregulation of levels of cAMP and Ca2+.

PMID- 19594743
TI  - Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder
      (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis.
AB  - Children with Down syndrome (DS) have a marked increase in susceptibility to
      Acute Megakaryoblastic Leukaemia (DS-AMKL) and the closely linked neonatal
      preleukaemic syndrome, Transient Myeloproliferative Disorder (DS-TMD). The
      distinct stages of DS-TMD and DS-AMKL provide an excellent tractable model to
      study leukaemogenesis. This review focuses on recent studies describing clinical,
      haematological and biological features of DS-AMKL and DS-TMD. The findings from
      these studies suggest that mutations in the key haemopoietic regulator GATA1
      (GATA binding protein 1) in DS-AMKL and DS-TMD may be useful in diagnosis and
      assessing minimal residual disease. These findings raise the possibility of
      population-based screening strategies for DS-TMD and the development of treatment
      to eliminate the preleukaemic TMD clone to prevent DS-AMKL. Advances in our
      understanding of perturbed haemopoiesis in DS, the role of GATA1 and of
      cooperating mutations are also discussed. These findings have implications for
      leukaemia biology more broadly given the frequency of acquired trisomy in other
      human leukaemias.

PMID- 19594744
TI  - Severe congenital neutropenia: a negative synergistic effect of multiple
      mutations of ELANE (ELA2) gene.

PMID- 19594745
TI  - Vascular density in childhood acute lymphoblastic leukaemia correlates to
      biological factors and outcome.
AB  - The issue of angiogenesis and its clinical relevance in childhood acute
      lymphoblastic leukaemia (ALL) is controversial. In the present study, microvessel
      density (MVD), analysed in 185 diagnostic bone marrow biopsies, was higher in T
      cell ALL compared to B-cell precursor (BCP)-ALL (P = 0.013). In the BCP group,
      cases with t(12;21) were characterized by a low MVD while patients with high
      hyperdiploid leukaemia (HeH, 51-61 chromosomes) showed a high MVD compared to
      other BCP patients (P = 0.001 and 0.002 respectively). There was a correlation
      between MVD and white blood cell (WBC) count in high-risk BCP patients (P =
      0.021). In addition, BCP patients with a high marrow reticulin fibre density and
      high MVD had an unfavourable outcome compared to the other BCP patients (P =
      0.002). The fraction of vessels in which lumina were filled with blasts (blast
      congested vessel fraction) correlated strongly with WBC count (P < 0.001). These
      findings indicate that the angiogenic process interacts with other stroma
      factors, such as reticulin fibre density, in its effect on outcome, and is
      coupled to both the ALL genotype and phenotype. One possible implication is that
      different subtypes of childhood ALL may respond differently to anti-angiogenic
      drugs as a supplement in first-line treatment.

PMID- 19594746
TI  - von Willebrand factor protects the Ca2+-dependent structure of the factor VIII
      light chain.
AB  - We have recently reported that cation-exchange iminodiacetate resin completely
      inactivated factor VIII (FVIII) by direct deprivation of metal ions,
      predominantly Ca2+, from its molecules, and that von Willebrand factor (VWF)
      protected FVIII antigen from resin-induced degradation. The present study was
      further developed to investigate this mechanism. Western blotting analysis and
      enzyme-linked immunosorbent assay showed that the antigenic structure of the
      FVIII light chain, especially the C2 domain, was completely impaired by the
      resin, whilst that of the heavy chain was little affected. However, the complex
      formation with VWF protected the C2 domain from the resin-induced degradation.
      The resin-treated C2 domain failed to interact with VWF and phospholipid.
      Furthermore, the addition of Ca2+ competitively blocked the resin-induced
      impairment of the C2 domain structure. These results demonstrate that VWF
      protects the Ca2+-dependent conformational structure of the FVIII light chain,
      especially the C2 domain, and may indicate that the C2 domain contains the Ca2+
      binding site(s).

PMID- 19594747
TI  - Detection of gene copy number aberrations in mantle cell lymphoma by a single
      quantitative multiplex PCR assay: clinicopathological relevance and prognosis
      value.
AB  - The t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL). Additional
      genetic alterations occur in the majority of cases. This study aimed to design a
      polymerase chain reaction (PCR) assay to determine the incidence and relevance of
      recurrent gene copy number aberrations in this disease. Forty-two MCL cases with
      frozen- or paraffin-embedded (FFPE) tissues were selected. Three different
      quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) assays were
      designed to simultaneously analyse eight genes (CDKN2A, RB1, ATM, CDK2, TP53,
      MYC, CDKN1B, MDM2), to analyse the 9p21 locus (CDKN2A/CDKN2B) and FFPE tissues.
      Gains of MYC, CDK2, CDKN1B, and MDM2 were observed in 10% of cases. Losses of
      RB1, CDKN2A, ATM or TP53 were observed in 38%, 31%, 24% and 10% of cases,
      respectively. Analysis of the 9p21 locus indicated that, in most cases, tumours
      displayed a complete inactivation of p14(ARF)/p15I(NK4B)/p16I(NK4A). CDKN2A and
      MYC aberrations were associated with a high MCL international prognostic index
      (MIPI). CDK2/MDM2 gains and CDKN2A/TP53 losses correlated with an unfavourable
      outcome. PCR experiments with frozen and FFPE-tissues indicated that our approach
      is valid in a routine diagnostic setting, providing a powerful tool that could be
      used for patient stratification in combination with MIPI in future clinical
      trials.

PMID- 19594748
TI  - NKG2D-mediated immunity underlying paroxysmal nocturnal haemoglobinuria and
      related bone marrow failure syndromes.
AB  - It is considered that a similar immune mechanism acts in the pathogenesis of bone
      marrow (BM) failure in paroxysmal nocturnal haemoglobinuria (PNH) and its related
      disorders, such as aplastic anaemia (AA) and myelodysplastic syndromes (MDS).
      However, the molecular events in immune-mediated marrow injury have not been
      elucidated. We recently reported an abnormal expression of stress-inducible NKG2D
      (natural-killer group 2, member D) ligands, such as ULBP (UL16-binding protein)
      and MICA/B (major histocompatibility complex class I chain-related molecules
      A/B), on granulocytes in some PNH patients and the granulocyte killing by
      autologous lymphocytes in vitro. The present study found that the expression of
      NKG2D ligands was common to both granulocytes and BM cells of patients with PNH,
      AA, and MDS, indicating their exposure to some incitement to induce the ligands.
      The haematopoietic colony formation in vitro by the patients' marrow cells
      significantly improved when their BM cells were pretreated with antibodies
      against NKG2D receptor, suggesting that the antibodies rescued haematopoietic
      cells expressing NKG2D ligands from damage by autologous lymphocytes with NKG2D.
      Clinical courses of patients with PNH and AA showed a close association of the
      expression of NKG2D ligands with BM failure and a favourable response to
      immunosuppressive therapy. We therefore propose that NKG2D-mediated immunity may
      underlie the BM failure in PNH and its-related marrow diseases.

PMID- 19594749
TI  - Nitrite directly vasodilates hypoxic vasculature via nitric oxide-dependent and 
      independent pathways.
AB  - BACKGROUND AND PURPOSE: It is postulated that nitrite requires reduction to
      nitric oxide in order to exert its relaxant effect upon isolated hypoxic vessels.
      Herein, we evaluate the relative contribution of nitric oxide and characterize
      the downstream mechanisms of nitrite-induced vasorelaxation. EXPERIMENTAL
      APPROACH: Aortic rings were treated with pharmacological agents and exposed to
      hypoxia (<1% O(2)). Following pre-constriction, nitrite (10 microM final) was
      added to appropriate baths; isometric tension was recorded throughout. KEY
      RESULTS: Nitrite (under hypoxic conditions at physiological pH) is capable of
      exerting physiological effects that cannot be completely inhibited by the
      inhibitor of soluble guanylate cyclase (sGC), 1H [1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one or a nitric oxide scavenger (carboxy-2-phenyl-4,4,5,5
      tetramethyl-imidazoline-1-oxyl-3-oxide). Simultaneous blockade of both sGC and
      cyclooxygenase (COX) completely inhibited the response to nitrite. With regard to
      the nitric oxide-dependent component, we confirm that aldehyde oxidase, but not
      xanthine oxidase or endothelial nitric oxide synthase, was important for the
      actions of nitrite in our model. CONCLUSIONS AND IMPLICATIONS: Nitric oxide
      generated from nitrite is not exclusively responsible for the physiological
      actions observed in isolated hypoxic vessels. Nitrite operates via different
      pathways dependent on the presence or absence of endothelium to produce
      vasorelaxation. In intact vessels, both sGC and COX enzymes appear to be
      important. Irrespective of this difference in relaxation mechanism, nitrite is
      capable of producing the same maximum relaxation, regardless of the presence of
      endothelium. Having investigated possible nitrite reduction sites, we confirm
      that aldehyde oxidase is important for the actions of nitrite.

PMID- 19594750
TI  - NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses
      inflammatory and nociceptive responses in in vitro and in vivo models.
AB  - BACKGROUND AND PURPOSE: We previously reported that NCX 2057, a compound
      comprising a nitric oxide (NO)-releasing moiety and the natural antioxidant,
      ferulic acid (FA), inhibits pro-inflammatory mediators through NO-mediated gene
      regulation. Here, we have assessed the activities of NCX 2057 in models of
      inflammatory and neuropathic pain, and characterized its effects on
      cyclooxygenase (COX)-1 and COX-2. EXPERIMENTAL APPROACH: Anti-nociceptive and
      anti-inflammatory activities of NCX 2057 were measured in vitro and in vivo in
      models of inflammatory (carrageenan) and neuropathic (chronic constriction
      injury; CCI) pain. Effects of NCX 2057 were measured on COX-1 and COX-2
      activities in RAW 264.7 macrophages. KEY RESULTS: NCX 2057 dose-dependently
      inhibited single motor unit responses to noxious mechanical stimulation (ID(50)=
      100 micromol kg(-1)) and wind-up responses in rats with paw inflammation induced
      by carrageenan. Moreover, NCX 2057 inhibited allodynic responses following CCI of
      the sciatic nerve [ipsilateral Paw Withdrawal Threshold (g): vehicle: 41.4 +/-
      3.3; NCX 2057: 76.3 +/- 4.8 FA: 37.9 +/- 15.5 at 175 micromol kg(-1)]. NCX 2057
      reversed carrageenan-induced hyperalgesic responses in mice and inhibited
      prostaglandin E(2) formation in paw exudates. Finally, NCX 2057 competitively
      inhibited COX-1 and COX-2 activities in whole RAW macophages (IC(50)= 14.7 +/-
      7.4 and 21.6 +/- 7.5 microM, respectively). None of these properties were
      exhibited by equivalent treatments with FA or standard NO donor compounds.
      CONCLUSIONS AND IMPLICATIONS: These studies indicate that NCX 2057 is effective
      in chronic inflammatory and neuropathic pain models, probably because of its
      particular combination of anti-COX, antioxidant and NO-releasing properties.

PMID- 19594751
TI  - Salicylate, an aspirin metabolite, specifically inhibits the current mediated by
      glycine receptors containing alpha1-subunits.
AB  - BACKGROUND AND PURPOSE: Aspirin or its metabolite sodium salicylate is widely
      prescribed and has many side effects. Previous studies suggest that targeting
      neuronal receptors/ion channels is one of the pathways by which salicylate causes
      side effects in the nervous system. The present study aimed to investigate the
      functional action of salicylate on glycine receptors at a molecular level.
      EXPERIMENTAL APPROACH: Whole-cell patch-clamp and site-directed mutagenesis were
      deployed to examine the effects of salicylate on the currents mediated by native
      glycine receptors in cultured neurones of rat inferior colliculus and by glycine
      receptors expressed in HEK293T cells. KEY RESULTS: Salicylate effectively
      inhibited the maximal current mediated by native glycine receptors without
      altering the EC(50) and the Hill coefficient, demonstrating a non-competitive
      action of salicylate. Only when applied simultaneously with glycine and
      extracellularly, could salicylate produce this antagonism. In HEK293T cells
      transfected with either alpha1-, alpha2-, alpha3-, alpha1beta-, alpha2beta- or
      alpha3beta-glycine receptors, salicylate only inhibited the current mediated by
      those receptors that contained the alpha1-subunit. A single site mutation of
      I240V in the alpha1-subunit abolished inhibition by salicylate. CONCLUSIONS AND
      IMPLICATIONS: Salicylate is a non-competitive antagonist specifically on glycine
      receptors containing alpha1-subunits. This action critically involves the
      isoleucine-240 in the first transmembrane segment of the alpha1-subunit. Our
      findings may increase our understanding of the receptors involved in the side
      effects of salicylate on the central nervous system, such as seizures and
      tinnitus.

PMID- 19594753
TI  - Protective effects of mildronate in an experimental model of type 2 diabetes in
      Goto-Kakizaki rats.
AB  - BACKGROUND AND PURPOSE: Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is
      an anti-ischaemic drug whose mechanism of action is based on its inhibition of L
      carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the
      balanced metabolism of fatty acids and carbohydrates, this study was carried out
      to investigate whether long-term mildronate treatment could influence glucose
      levels and prevent diabetic complications in an experimental model of type 2
      diabetes in Goto-Kakizaki (GK) rats. EXPERIMENTAL APPROACH: GK rats were treated
      orally with mildronate at doses of 100 and 200 mg.kg(-1) daily for 8 weeks.
      Plasma metabolites reflecting glucose and lipids, as well as fructosamine and
      beta-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by
      ultra performance liquid chromatography with tandem mass spectrometry. An
      isolated rat heart ischaemia-reperfusion model was used to investigate possible
      cardioprotective effects. Pain sensitivity was measured with a tail-flick latency
      test. KEY RESULTS: Mildronate treatment significantly decreased L-carnitine
      concentrations in rat plasma and gradually decreased both the fed- and fasted
      state blood glucose. Mildronate strongly inhibited fructosamine accumulation and
      loss of pain sensitivity and also ameliorated the enhanced contractile
      responsiveness of GK rat aortic rings to phenylephrine. In addition, in
      mildronate-treated hearts, the necrosis zone following coronary occlusion was
      significantly decreased by 30%. CONCLUSIONS AND IMPLICATIONS: These results
      demonstrate for the first time that in GK rats, an experimental model of type 2
      diabetes, mildronate decreased L-carnitine contents and exhibited
      cardioprotective effects, decreased blood glucose concentrations and prevented
      the loss of pain sensitivity. These findings indicate that mildronate treatment
      could be beneficial in diabetes patients with cardiovascular problems.

PMID- 19594752
TI  - Intracellular sequestration of amiodarone: role of vacuolar ATPase and
      macroautophagic transition of the resulting vacuolar cytopathology.
AB  - BACKGROUND AND PURPOSE: Tissue deposits of the anti-arrhythmic drug amiodarone
      are a major source of side effects (skin discoloration, etc.). We addressed the
      mechanism of the concentration of amiodarone in cells, and characterized the
      resulting vacuolar cytopathology and its evolution towards macroautophagy.
      EXPERIMENTAL APPROACH: Sequestration of amiodarone in human cells (macrophages,
      smooth muscle cells, HEK 293a cells) was evaluated using its violet fluorescence
      and cytopathology using GFP-conjugated subcellular markers. Autophagic signalling
      was probed by immunoblotting for the effector protein LC3. A patient biopsy of
      amiodarone-induced blue-gray skin discoloration was investigated for the presence
      of macroautophagy (immunofluorescence for LC3). KEY RESULTS: Most of the
      amiodarone (1-20 microM, 4-24 h) captured by cultured cells (macrophages were
      most avid) was present in enlarged vacuoles. The specific vacuolar ATPase (V
      ATPase) inhibitors, bafilomycin A1 or FR167356, prevented vacuolization and drug
      uptake. Vacuoles in HEK 293a cells were positive for markers of late endosomes
      and lysosomes (GFP-Rab7, -CD63) and for an effector of macroautophagy, GFP-LC3.
      The vacuoles accumulated endogenous LC3 and filled with lipids (Nile red
      staining) following longer amiodarone treatments (> or =24 h). The
      electrophoretic mobility of both GFP-LC3 and endogenous LC3 changed, showing
      activation in response to amiodarone. Paraffin tissue sections of the pigmented
      skin exhibited granular LC3 accumulation in superficial dermis macrophages.
      CONCLUSION AND IMPLICATIONS: Vacuolar sequestration of amiodarone occurs at
      concentrations close to therapeutic levels, is mediated by V-ATPase and evolves
      towards persistent macroautophagy and phospholipidosis. This cytopathology is not
      cell type specific, but tissue macrophages appear to be particularly susceptible.

PMID- 19594754
TI  - Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon
      gamma in HaCaT cells, a human keratinocyte cell line.
AB  - BACKGROUND AND PURPOSE: The macrophage-derived chemokine (MDC/CCL22) is a
      prototypic Th2-type chemokine intimately involved in Th2-skewed allergic
      diseases, such as atopic dermatitis and asthma. The statins (3-hydroxy-3-methyl
      glutaryl coenzyme A reductase inhibitors) have been demonstrated to relieve
      allergic inflammation. However, the immunological effects and mechanisms of
      statins against atopic dermatitis remain unknown, at least in vitro. This study
      aimed to define how different statins affect MDC expression in HaCaT cells, a
      human keratinocyte cell line. EXPERIMENTAL APPROACH: To measure the effects of
      statins on MDC expression in HaCaT cells, we used a cell viability assay, reverse
      transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and
      Western blotting analyses. KEY RESULTS: Fluvastatin, but not atorvastatin or
      simvastatin, inhibited MDC expression induced by interferon (IFN)-gamma and NF
      kappaB activation. A NF-kappaB inhibitor, but not a STAT1 inhibitor, suppressed
      MDC expression in HaCaT cells. Further, inhibition of p38 mitogen-activated
      protein kinases (MAPKs) significantly suppressed IFN-gamma-induced MDC expression
      and NF-kappaB activation. Interestingly, fluvastatin suppressed IFN-gamma-induced
      NF-kappaB activation in parallel with p38 MAPK phosphorylation. CONCLUSIONS AND
      IMPLICATIONS: These results indicate that fluvastatin inhibited expression of the
      CC chemokine MDC induced by IFN-gamma in HaCaT cells, by inhibiting NF-kappaB
      activation via the p38 MAPK pathway. This blockade of a Th2 chemokine by
      fluvastatin may suppress the infiltration of Th2 cells into skin lesions and
      lessen the skin inflammation seen in atopic dermatitis, suggesting a potential
      therapeutic use of fluvastatin for this condition.

PMID- 19594755
TI  - Central antinociception induced by mu-opioid receptor agonist morphine, but not
      delta- or kappa-, is mediated by cannabinoid CB1 receptor.
AB  - BACKGROUND AND PURPOSE: It has been demonstrated that cannabinoids evoke the
      release of endogenous opioids to produce antinociception; however, no information
      exists regarding the participation of cannabinoids in the antinociceptive
      mechanisms of opioids. The aim of the present study was to determine whether
      endocannabinoids are involved in central antinociception induced by activation of
      mu-, delta- and kappa-opioid receptors. EXPERIMENTAL APPROACH: Nociceptive
      threshold to thermal stimulation was measured according to the tail-flick test in
      Swiss mice. Morphine (5 microg), SNC80 (4 microg), bremazocine (4 microg), AM251
      (2 and 4 microg), AM630 (2 and 4 microg) and MAFP (0.1 and 0.4 microg) were
      administered by the intracerebroventricular route. KEY RESULTS: The CB(1)
      selective cannabinoid receptor antagonist AM251 completely reversed the central
      antinociception induced by morphine in a dose-dependent manner. In contrast, the
      CB(2)-selective cannabinoid receptor antagonist AM630 did not antagonize this
      effect. Additionally, the administration of the anandamide amidase inhibitor,
      MAFP, significantly enhanced the antinociception induced by morphine. In
      contrast, the antinociceptive effects of delta- and kappa-opioid receptor
      agonists were not affected by the cannabinoid antagonists. The antagonists alone
      caused no hyperalgesic or antinociceptive effects. CONCLUSIONS AND IMPLICATIONS:
      The results provide evidence for the involvement of cannabinoid CB(1) receptors
      in the central antinociception induced by activation of mu-opioid receptors by
      the agonist morphine. The release of endocannabinoids appears not to be involved
      in central antinociception induced by activation of kappa- and delta-opioid
      receptors.

PMID- 19594756
TI  - Molecular mechanisms for the persistent bronchodilatory effect of the beta 2
      adrenoceptor agonist salmeterol.
AB  - BACKGROUND: Beta(2)-adrenoceptor agonists are effective bronchodilators. In vitro
      studies demonstrated long-lasting airway smooth muscle relaxation by salmeterol
      after washout, the quick disappearance of this effect in presence of antagonists
      and its recovery after antagonist removal. Current explanations invoke salmeterol
      accumulation in the membrane ('diffusion microkinetic' model) or the existence of
      salmeterol-binding 'exosites'. An alternative model based on 'rebinding' of a
      dissociated ligand to the receptor molecules also produces an apparent decrease
      in the ligand's dissociation rate in the absence of competing ligands. PURPOSE
      AND APPROACH: Computer-assisted simulations were performed to follow the receptor
      occupation by a salmeterol-like ligand and a competing ligand as a function of
      time. The aptness of the models to describe the above in vitro findings was
      evaluated. KEY RESULTS: The 'diffusion microkinetic' model is sufficient to
      explain a long-lasting beta(2)-adrenoceptor stimulation and reassertion as long
      as the membrane harbors a high concentration of the agonist. At lower
      concentration, 'rebinding' and, in second place, 'exosite' binding are likely to
      become operational. CONCLUSIONS AND IMPLICATIONS: The 'rebinding' and 'exosite'
      binding mechanisms take place at a sub-cellular/molecular scale. Pending their
      demonstration by experiments on appropriate, simple models such as intact cells
      or membranes thereof, these mechanisms remain hypothetical in the case of
      salmeterol. Airway smooth muscle contraction could also be governed by additional
      mechanisms that are particular to this macroscopic approach.

PMID- 19594758
TI  - Curcumin suppresses expression of low-density lipoprotein (LDL) receptor, leading
      to the inhibition of LDL-induced activation of hepatic stellate cells.
AB  - BACKGROUND AND PURPOSE: Obesity is often accompanied by hypercholesterolemia
      characterized by elevated levels of plasma low-density lipoprotein (LDL) and
      associated with non-alcoholic steatohepatitis, which could progress to hepatic
      fibrosis. Hepatic stellate cells (HSCs) are the major effectors of hepatic
      fibrogenesis. This study aims to clarify effects of LDL on activation of HSC, to
      evaluate roles of curcumin in suppressing these effects and to further elucidate
      the underlying molecular mechanisms. EXPERIMENTAL APPROACHES: HSCs were prepared
      from rats and cell proliferation was measured by cell proliferation assays (MTS
      assays). Transient transfection assays were performed to evaluate gene promoter
      activities. Real-time polymerase chain reaction and Western blotting were used to
      analyse the expression of genes. KEY RESULTS: LDL stimulated HSC activation in
      vitro, which was attenuated by curcumin. Curcumin reduced the abundance of LDL
      receptor (LDLR) in activated HSCs, decreasing cellular cholesterol. Curcumin
      dependent activation of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) differentially regulated the expression of the transcription factors,
      sterol regulatory element-binding proteins (SREBPs), in activated HSCs, resulting
      in the suppression of LDLR gene expression. CONCLUSIONS AND IMPLICATIONS:
      Curcumin suppressed LDLR gene expression in activated HSCs in vitro by activating
      PPARgamma and differentially regulating gene expression of SREBPs, reducing
      cellular cholesterol and attenuating the stimulatory effects of LDL on HSC
      activation. These results provide novel insights into the roles and mechanisms of
      curcumin in the inhibition of LDL-induced HSC activation. This curcumin, a
      constituent of turmeric, may be useful in preventing hypercholesterolemia
      associated hepatic fibrogenesis.

PMID- 19594759
TI  - Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo
      following co-administration of L-tryptophan.
AB  - BACKGROUND AND PURPOSE: Gaboxadol has been in development for treatment of
      chronic pain and insomnia. The clinical use of gaboxadol has revealed that
      adverse effects seem related to peak serum concentrations. The aim of this study
      was to investigate the mechanism of intestinal absorption of gaboxadol in vitro
      and in vivo. EXPERIMENTAL APPROACH: In vitro transport investigations were
      performed in Caco-2 cell monolayers. In vivo pharmacokinetic investigations were
      conducted in beagle dogs. Gaboxadol doses of 2.5 mg.kg(-1) were given either as
      an intravenous injection (1.0 mL.kg(-1)) or as an oral solution (5.0 mL.kg(-1)).
      KEY RESULTS: Gaboxadol may be a substrate of the human proton-coupled amino acid
      transporter, hPAT1 and it inhibited the hPAT1-mediated L-[(3)H]proline uptake in
      Caco-2 cell monolayers with an inhibition constant K(i) of 6.6 mmol.L(-1). The
      transepithelial transport of gaboxadol was polarized in the apical to basolateral
      direction, and was dependent on gaboxadol concentration and pH of the apical
      buffer solution. In beagle dogs, the absorption of gaboxadol was almost complete
      (absolute bioavailability, F(a), of 85.3%) and T(max) was 0.46 h. Oral co
      administration with 2.5-150 mg.kg(-1) of the PAT1 inhibitor, L-tryptophan,
      significantly decreased the absorption rate constant, k(a), and C(max), and
      increased T(max) of gaboxadol, whereas the area under the curve and clearance of
      gaboxadol were constant. CONCLUSIONS AND IMPLICATIONS: The absorption of
      gaboxadol across the luminal membrane of the small intestinal enterocytes is
      probably mediated by PAT1. This knowledge is useful for reducing gaboxadol
      absorption rates in order to decrease peak plasma concentrations.

PMID- 19594757
TI  - Resolvins and protectins: mediating solutions to inflammation.
AB  - Resolution of inflammation has historically been viewed as a passive process,
      occurring as a result of the withdrawal of pro-inflammatory signals, including
      lipid mediators such as leukotrienes and prostaglandins. Thus, most anti
      inflammatory drugs have traditionally targeted primarily mediator pathways that
      are engaged at the onset of inflammation. Only recently has it been established
      that inflammation resolution is an active process with a distinct set of chemical
      mediators. Several clinical and epidemiological studies have identified
      beneficial effects of polyunsaturated fatty acids (PUFAs) for a variety of
      inflammatory diseases, yet without mechanistic explanations for these beneficial
      effects. Resolvins and protectins are recently identified molecules that are
      generated from omega-3 PUFA precursors and can orchestrate the timely resolution
      of inflammation in model systems. Dysregulation of pro-resolving mediators is
      associated with diseases of prolonged inflammation, so designing pharmacological
      mimetics of naturally occurring pro-resolving mediators offers exciting new
      targets for drug design. This review describes the discovery and synthesis of
      these novel lipid mediators, their receptors and mechanisms of action, and
      summarizes the studies to date that have uncovered roles for resolvins and
      protectins in disease states.

PMID- 19594760
TI  - Sominone enhances neurite outgrowth and spatial memory mediated by the
      neurotrophic factor receptor, RET.
AB  - BACKGROUND AND PURPOSE: Orally administered withanoside IV (a compound isolated
      from the roots of Withania somnifera) improved memory deficits in mice with a
      model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35).
      Sominone, an aglycone of withanoside IV, was identified as an active metabolite
      after oral administration of withanoside IV. We aimed to identify receptors or
      associated molecules of sominone, and to investigate the effects of sominone on
      memory in normal mice. EXPERIMENTAL APPROACH: Phosphorylation levels of 71
      molecules were compared between control and sominone-stimulated cortical cultured
      cells to search for target molecules of sominone. Object location memory and
      neurite density in the brain were evaluated in sominone-injected mice. KEY
      RESULTS: Phosphorylation of RET (a receptor for the glial cell line-derived
      neurotrophic factor, GDNF) was increased in neurons by sominone, without
      affecting the synthesis and secretion of GDNF. Knockdown of RET prevented
      sominone-induced outgrowths of axons and dendrites. After a single i.p. injection
      of sominone into normal mice, they could better memorize scenery information than
      control mice. Sixty minutes after sominone injection, RET phosphorylation was
      increased, particularly in the hippocampus of mice. After the memory tests, the
      densities of axons and dendrites were increased in the hippocampus by sominone
      administration. CONCLUSIONS AND IMPLICATIONS: Sominone could reinforce the
      morphological plasticity of neurons by activation of the RET pathway and thus
      enhance memory. Sominone, a compound with low molecular weight, may be a GDNF
      independent stimulator of the RET pathway and/or a novel modulator of RET
      signalling.

PMID- 19594761
TI  - Compounds from Sichuan and Melegueta peppers activate, covalently and non
      covalently, TRPA1 and TRPV1 channels.
AB  - BACKGROUND AND PURPOSE: Oily extracts of Sichuan and Melegueta peppers evoke
      pungent sensations mediated by different alkylamides [mainly hydroxy-alpha
      sanshool (alpha-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We
      assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1
      (TRPV1), two chemosensory ion channels, participate in these pungent sensations.
      EXPERIMENTAL APPROACH: The structure-activity relationships of these molecules on
      TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using
      calcium and voltage imaging on dissociated dorsal root ganglia neurons and human
      embryonic kidney 293 cells expressing the wild-type channels or specific cysteine
      mutants using glutathione trapping as a model to probe TRPA1 activation. In
      addition, using Trpv1 knockout mice, the compounds' aversive responses were
      measured in a taste brief-access test. KEY RESULTS: For TRPA1 activation, the cis
      C6 double bond in the polyenic chain of alpha-SOH was critical, whereas no
      structural specificity was required for activation of TRPV1. Both 6-shogaol and 6
      paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an
      abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels.
      Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these
      compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice
      retained sensitivity to 6-shogaol but were not responsive to alpha-SOH.
      CONCLUSIONS AND IMPLICATIONS: The pungent nature of components of Sichuan and
      Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and
      may explain the aversive properties of these compounds.

PMID- 19594763
TI  - Breast tumor resembling the tall cell variant of papillary thyroid carcinoma.
AB  - We describe the case of a 66-year-old woman with a palpable mass in her left
      breast. Although the diagnosis on core biopsy was an intraductal papilloma, the
      surgically excised lesion showed it to be an infiltrating carcinoma which
      appeared to arise in a complex sclerosing lesion and is similar to the recently
      described breast tumor resembling the tall cell variant of papillary thyroid
      carcinoma.

PMID- 19594765
TI  - Lack of evidence for OSMR and RET gene mutations in a Chinese family with
      friction melanosis.
AB  - BACKGROUND: Friction melanosis (FM) is a common dermatological disorder. Although
      cases have been reported, familial FM is rare. FM and macular amyloidosis (MA)
      have been hypothesized to be identical clinical conditions, and cutaneous lichen
      amyloidosis (CLA) is linked to mutations in the OSMR (oncostatin M receptor) or
      RET (receptor tyrosine kinase) genes. AIM: To evaluate the OSMR and RET gene
      mutations in a Chinese family with FM. Methods. We investigated a family with FM
      with six affected members in four successive generations. All 17 exons of the
      OSMR and 19 exons of the RET genes were screened for mutation by PCR, and
      restriction enzyme digestion assays for RET codon 634 mutations were performed
      for selected members of the family. RESULTS: Based on the pedigree
      characteristics, we suggest an autosomal dominant mode of inheritance in this FM
      family. We did not detect any mutations in the OSMR or RET genes. CONCLUSIONS: We
      report a rare case of familial FM. Genes other than OSMR and RET may be involved
      in the pathogenesis of this family.

PMID- 19594764
TI  - A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment
      of patients with papulopustular rosacea: a randomized open-label clinical trial.
AB  - BACKGROUND: There are various treatment options available for rosacea, depending
      on the subtype, but treatment is still generally unsatisfactory. Some reports
      have indicated beneficial effects of topical pimecrolimus. AIM: To compare the
      efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the
      treatment of patients with papulopustular rosacea (PR). METHODS: A group of 49
      patients with PR was investigated in this single-centre, randomized, open-label
      study. Patients were randomly assigned treatment with either pimecrolimus 1%
      cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the
      inflammatory lesion count, the severity of facial erythema and telangiectasia,
      Physician's Global Assessment (PGA), and safety and tolerability at baseline and
      at weeks 3, 6, 9 and 12. RESULTS: In total, 48 patients completed the study. Both
      treatments were very effective in the treatment of PR. There were no significant
      differences between the treatments in inflammatory lesion counts, overall
      erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05).
      Neither treatment produced any clinically relevant improvement in telangiectasia.
      CONCLUSION: Pimecrolimus cream is no more efficacious than metronidazole cream in
      the treatment of PR.

PMID- 19594762
TI  - Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and
      therapeutic potential.
AB  - N-methyl-D-aspartate receptors (NMDARs) are ion channels gated by glutamate, the
      major excitatory neurotransmitter in the mammalian central nervous system (CNS).
      They are widespread in the CNS and are involved in numerous physiological and
      pathological processes including synaptic plasticity, chronic pain and psychosis.
      Aberrant NMDAR activity also plays an important role in the neuronal loss
      associated with ischaemic insults and major degenerative disorders including
      Parkinson's and Alzheimer's disease. Agents that target and alter NMDAR function
      may, thus, have therapeutic benefit. Interestingly, NMDARs are endowed with
      multiple extracellular regulatory sites that recognize ions or small molecule
      ligands, some of which are likely to regulate receptor function in vivo. These
      allosteric sites, which differ from agonist-binding and channel-permeation sites,
      provide means to modulate, either positively or negatively, NMDAR activity. The
      present review focuses on allosteric modulation of NMDARs containing the NR2B
      subunit. Indeed, the NR2B subunit confers a particularly rich pharmacology with
      distinct recognition sites for exogenous and endogenous allosteric ligands.
      Moreover, NR2B-containing receptors, compared with other NMDAR subtypes, appear
      to contribute preferentially to pathological processes linked to overexcitation
      of glutamatergic pathways. The actions of extracellular H+, Mg2+, Zn2+, of
      polyamines and neurosteroids, and of the synthetic compounds ifenprodil and
      derivatives ('prodils') are presented. Particular emphasis is put upon the
      structural determinants and molecular mechanisms that underlie the effects
      exerted by these agents. A better understanding of how NR2B-containing NMDARs
      (and NMDARs in general) operate and how they can be modulated should help define
      new strategies to counteract the deleterious effects of dysregulated NMDAR
      activity.

PMID- 19594766
TI  - Effect of topical insulin on cutaneous wound healing in rats with or without
      acute diabetes.
AB  - BACKGROUND: Diabetes is a condition known even in its early stages to impair the
      normal course of wound healing, thus leading to chronic wounds. The role of
      insulin in the regulation of energy metabolism, protein synthesis, cell
      differentiation and growth suggests that this hormone could also play an
      essential role in regulation of wound healing. AIM: To determine the effects of
      topical insulin administration on wound healing in rats with or without acute
      diabetes. METHODS: This study was conducted using four groups of male Sprague
      Dawley rats: (i) nondiabetic rats receiving topical insulin (n = 7), (ii)
      nondiabetic rats receiving topical sterile water (n = 7), (iii) diabetic rats
      receiving topical insulin (n = 7) and (iv) diabetic rats receiving topical
      sterile water (n = 7). Wound healing was assessed by wound contraction rate,
      complete epithelialization time and histological results. RESULTS: Topical
      insulin enhanced wound healing by shortening the time needed for complete
      epithelialization in both the nondiabetic and acute diabetic groups. The
      histological observations supported the planimetric results in both groups.
      CONCLUSIONS: This study revealed that topical insulin application to cutaneous
      wounds accelerates wound healing in rats with or without acute diabetes.

PMID- 19594767
TI  - Spitz naevus is rare in Korea.
AB  - BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare
      the epidemiology and clinicopathological features of Spitz naevi in Koreans with
      lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients
      diagnosed over 10 years at 17 university hospitals in Korea were analysed.
      RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most
      patients (75%) the Spitz naevi had been present for > 6 months. The size of the
      lesion was relatively large. Histologically, most of the lesions (54%) were the
      dermal type and pigmentation was common (49% of lesions). Immunohistochemical
      study found that all of the 34 lesions were positive for S-100 protein but only
      14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The
      lesions were more commonly larger, pigmented, and of the dermal type than
      reported in western countries.

PMID- 19594768
TI  - A retrospective analysis of 34 patients with cutaneous sarcoidosis assessed in a
      dermatology department.
AB  - BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown
      aetiology, which most often involves the lungs and lymphatic system. Cutaneous
      involvement is found in approximately 25% of cases of sarcoid. Most previous
      studies of cutaneous sarcoidosis have been drawn from populations with defined
      pulmonary disease, so may represent a population with more systemic involvement.
      OBJECTIVE: We describe a cohort of patients with cutaneous sarcoid seen in a
      dermatology department. METHODS: Case records were reviewed for patients with a
      histopathological diagnosis of noncaseating sarcoidal granuloma on skin biopsy,
      taken between 1996 and 2005. RESULTS: In total, 34 patient records were analysed;
      21 patients were found to have extracutaneous systemic sarcoid and 10 patients
      had sarcoid localized to the skin. Patients with lupus pernio and with ulcerated
      sarcoid lesions all had extracutaneous disease. No other cutaneous features,
      including the extent of cutaneous disease, were found to be predictive of
      systemic involvement. CONCLUSIONS: All patients presenting to a dermatology
      department with cutaneous sarcoidal granulomas require investigation for systemic
      sarcoid. Our data suggest that approximately 30% of patients seen in a
      dermatology clinic with cutaneous sarcoidal granulomas will have disease
      apparently limited to the skin.

PMID- 19594769
TI  - Effects of blood glucose fluctuation on skin biophysical properties, structure
      and antioxidant status in an animal model.
AB  - BACKGROUND: Intermittent blood-glucose fluctuation (BGF) can accelerate diabetes
      and its complications, but it is still unknown whether BGF can damage the skin of
      patients with diabetes. AIM: To investigate the effects of repetitive fluctuation
      in blood glucose concentration on the biophysical properties, structure and
      antioxidant capacity of diabetic mouse skin. METHODS: Mice with alloxan-induced
      diabetes were injected with glucose three times daily to induce repetitive BGF.
      Six weeks later, skin elasticity and skin hydration were measured to evaluate
      skin water-holding capacity and contraction function. The histological changes of
      skin were also studied, using haematoxylin and eosin. In addition, we compared
      levels of blood sugar and advanced glycation end products (AGEs), the activities
      of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and
      hydroxyproline in the skin of normal mice and diabetic mice with or without BGF.
      RESULTS: The diabetic mice with BGF displayed an 18.6% increase in blood sugar
      level, an 11.3% increase in AGEs content and a 13.1% increase in MDA content
      compared with the diabetic mice (P < 0.01). There was a greater reduction in skin
      elasticity, skin hydration, hydroxyproline content and SOD activity in the
      diabetic mice with BGF (P < 0.01). Histological examination showed that BGF
      enhanced skin lesions in diabetic mice. CONCLUSIONS: Repetitive fluctuation in
      blood-glucose concentration produced a marked detrimental effect on skin
      structure and function in diabetic mice. The deleterious effects of BGF on skin
      appeared to due at least partly to the oxidative stress.

PMID- 19594770
TI  - Gender differences in circulating bubble production after SCUBA diving.
AB  - OBJECTIVE: Differences in circulating bubble production have been described after
      exposures in altitude chambers between men and women. The present study was
      designed to examine gender differences in circulating bubble production after a
      dive. METHODS: Fifty-two men and 52 women performed the same dive profile (25 min
      to 35 m). Circulating bubbles were detected by continuous wave Doppler. Tests
      were conducted at sea in a boat, at 10-min intervals for 1 h after surfacing.
      Signals were graded according to the Spencer scale. The categorical data were
      then converted to a single number reflecting total bubble activity using the KISS
      index. RESULTS: Considering each measurement period, bubble grade was higher in
      men than women 30, 40 and 50 min postdive. On the contrary, bubble grade was
      comparable between men and women 10, 20 and 60 min after the dive. KISS index was
      significantly higher in men than women (6.77 [0.65-32.3] versus 0.91 [0-22.9],
      P<0.02). KISS index was significantly correlated with age, weight and body fat
      mass in the whole population and in the men and women separately. Postmenopausal
      women had a higher KISS index (42 [15-47]) when compared with premenopausal women
      and men older than 50 years. No difference in bubble production was found
      according to the use of oral contraceptive pills or the phase of the menstrual
      cycle. CONCLUSION: Overall, we observed fewer circulating bubbles in women than
      in men after an open sea SCUBA dive. This difference disappeared in the
      postmenopausal women.

PMID- 19594771
TI  - Metabolic syndrome and cardiovascular risk in renal transplant recipients:
      effects of statin treatment.
AB  - BACKGROUND: Renal transplant recipients (RTR) have high risk for cardiovascular
      disease (CVD). They also have high prevalence of insulin resistance and metabolic
      syndrome (MS). Statin treatment reduces CVD risk in RTR. The aim was to study MS
      as CVD risk factor in RTR, and to investigate the effect of statin treatment in
      RTR with MS. METHODS: In total, 1706 non-diabetic RTR from the Assessment of
      Lescol in Renal Transplantation trial were followed for 7-8 yr. The captured
      endpoints included major adverse cardiac events [MACE, defined as cardiac death
      (CD), non-fatal myocardial infarction or coronary revascularization procedure],
      and CD. MS was defined at baseline according to Adult Treatment Panel III
      definition with waist girth replaced by body mass index > or =30 kg/m2. RESULTS:
      MS was diagnosed in 32% of the patients. During the follow-up, MACE incidence was
      16% in those with MS and 11% in those without MS (p < 0.001). Statin treatment
      reduced MACE risk by 53% in the group with MS. CD risk was 74% higher in RTR with
      MS (p = 0.012), and statin treatment reduced CD risk in those with MS (p = 0.03).
      CONCLUSIONS: RTR with MS have increased risk for CVD. RTR with MS are an easily
      identifiable group of patients who benefit from statin treatment.

PMID- 19594772
TI  - The potential role of C-reactive protein in distinguishing cytomegalovirus from
      tuberculosis and bacterial infections in renal transplant recipients.
AB  - INTRODUCTION: The delay in the diagnosis of infections can be deleterious in
      renal transplant recipients. Thus, laboratory tests leading to an earlier
      diagnosis are very useful for these patients. PURPOSE: To assess the behavior of
      C-reactive protein (CRP) in renal transplant recipients with a diagnosis of
      cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI).
      METHODS: A retrospective analysis of 129 patients admitted at our hospital, from
      2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical
      analysis was done and values were expressed as medians, range. RESULTS: When CRP
      levels were compared among the groups with CMV disease, TB or BI, the group with
      CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB
      and BI (p < 0.05) groups. The area under the receiver-operating characteristics
      curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in
      100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5
      mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP
      (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease
      subgroups, respectively (p < 0.05). CONCLUSION: The measurement of CRP levels may
      be a useful tool for differentiating CMV infection from the other types
      (bacterial or TB) of infection in kidney transplant recipients.

PMID- 19594779
TI  - The importance of cutting angles while using a scalpel.

PMID- 19594773
TI  - The impact of reduced immunosuppression on graft outcomes in elderly renal
      transplant recipients.
AB  - Optimal immunosuppression (IS) for elderly kidney transplant recipients is
      unknown. We conducted a retrospective cohort study of recipients aged 60 yr or
      older to examine the impact of reduced IS on graft outcomes. Group 1 patients (n
      = 101) were initiated on mycophenolate mofetil 2 g/d and tacrolimus, target level
      10-12 ng/mL; Group 2 patients (n = 88) with 1 g/d and 8-10 ng/mL, respectively.
      Dose adjustments were made as required. The groups were comparable except for
      diabetes, end-stage renal disease duration, and induction. Mycophenolate mofetil
      dose was reduced in 62% and 38% of the patients, respectively (p < 0.01).
      Patients were followed for 23.8 +/- 14.2 and 21.3 +/- 11.8 months post-transplant
      (p = 0.2). Twenty-seven cases in Group 1 (26.7%) and eight in Group 2 (9.1%) lost
      their grafts (p = 0.01); 19 (18.8%) and 7 (8.0%) cases in each group because of
      death, respectively (p = 0.09). Sixteen patients in Group 1 (15.8%) and 18 in
      Group 2 (20.5%) experienced acute rejection (p = 0.36). Patients in Group 2 had a
      lower risk of graft loss compared with those in Group 1 [adjusted hazard ratio
      (HR): 0.27, p = 0.006, 95% CI: 0.11-0.69]. There were no significant differences
      between the groups regarding graft function, BK virus nephropathy, and CMV
      infection. Our results suggest that reduction in overall IS in this group was
      associated with improved graft and patient survival.

PMID- 19594780
TI  - Use of the tympanoplasty blade to facilitate auricular surgery.

PMID- 19594781
TI  - Re: Eyelid tightening and improved eyelid aperture through nonablative fractional
      resurfacing.

PMID- 19594782
TI  - Procedural dermatology fellow evaluation and the accreditation council for
      graduate medical education accreditation process.

PMID- 19594786
TI  - Access to health and social services for IDU: the impact of a medically
      supervised injection facility.
AB  - INTRODUCTION AND AIMS: Injection drug users (IDU) often experience barriers to
      conventional health-care services, and consequently might rely on acute and
      emergency services. This study sought to investigate IDU perspectives regarding
      the impact of supervised injection facility (SIF) use on access to health-care
      services. DESIGN AND METHODS: Semi-structured qualitative interviews were
      conducted with 50 Vancouver-based IDU participating in the Scientific Evaluation
      of Supervised Injecting cohort. Audio-recorded interviews elicited IDU
      perspectives regarding the impact of SIF use on access to health and social
      services. Interviews were transcribed verbatim and a thematic analysis was
      conducted. RESULTS: Fifty IDU, including 21 women, participated in this study.
      IDU narratives indicate that the SIF serves to facilitate access to health care
      by providing much-needed care on-site and connects IDU to external services
      through referrals. Participants' perspectives suggest that the SIF has
      facilitated increased uptake of health and social services among IDU. DISCUSSION
      AND CONCLUSIONS: Although challenges related to access to care remain in many
      settings, SIF have potential to promote health by facilitating enhanced access to
      health-care and social services through a model of care that is accessible to
      high-risk IDU.

PMID- 19594787
TI  - Overdose deaths following previous non-fatal heroin overdose: record linkage of
      ambulance attendance and death registry data.
AB  - INTRODUCTION AND AIMS: Experiencing previous non-fatal overdoses have been
      identified as a predictor of subsequent non-fatal overdoses; however, few studies
      have investigated the association between previous non-fatal overdose experiences
      and overdose mortality. We examined overdose mortality among injecting drug users
      who had previously been attended by an ambulance for a non-fatal heroin overdose.
      DESIGN AND METHODS: Using a retrospective cohort design, we linked data on non
      fatal heroin overdose cases obtained from ambulance attendance records in
      Melbourne, Australia over a 5-year period (2000-2005) with a national death
      register. RESULTS: 4884 people who were attended by ambulance for a non-fatal
      heroin overdose were identified. One hundred and sixty-four overdose deaths
      occurred among this cohort, with an average overdose mortality rate of 1.20 per
      100 person-years (95% CI, 1.03-1.40). Mortality rate decreased 10-fold after 2000
      coinciding with widely reported declines in heroin availability. Being male, of
      older age (>35 years) and having been attended multiple times for previous non
      fatal overdoses were associated with increased mortality risk. DISCUSSION AND
      CONCLUSIONS: As the first to show a direct association between non-fatal overdose
      and subsequent overdose mortality, this study has important implications for the
      prevention of overdose mortality. This study also shows the profound effect of
      macro-level heroin market dynamics on overdose mortality.

PMID- 19594788
TI  - Evaluation of a training program to improve clinicians' assessment of patient
      stability.
AB  - INTRODUCTION AND AIMS: Public clinics in New South Wales (NSW), Australia play a
      central role in inducting and stabilising opioid dependent clients onto treatment
      before transfer to a community pharmacy. Clinical assessment of stability is a
      vital skill in ensuring that clients are appropriately and effectively
      transferred. A two-hour clinical training program was delivered to staff at 31
      public clinics, that aimed to improve staff confidence in assessing client
      stability, and skills in negotiating the transfer of clients to community
      pharmacies. DESIGN AND METHODS: Pre- and post-training evaluation was conducted
      examining self-ratings of confidence and ability in the assessment of client
      stability, and the perceived utility of a clinical algorithm to improve
      assessments. Follow-up was conducted 3 to 6 months post-training assessing
      individual and clinic level changes in clinical practice. RESULTS: 205 staff
      completed pre- and post-training questionnaires. Staff demonstrated a moderate
      level of self-reported baseline knowledge and skills in assessing client
      stability (mean = 6.5; 1 = poor; 10 = excellent) that improved when re-assessed
      following the training (mean = 8.0). 76 staff responded to the follow-up
      questionnaire. > or = 75% reported some level of improvement in their approach to
      clinical practice regarding stability assessment, and 59% reported being more
      effective in identifying clients appropriate for community pharmacy transfer. Of
      19 public clinics, 14 reported an increased focus on stability assessment. Nine
      clinics reported barriers to achieving changes in clinical practice. DISCUSSION
      AND CONCLUSIONS: This evaluation demonstrates that it is possible to implement a
      targeted clinical training package to staff that translates into positive changes
      in clinical practice.

PMID- 19594789
TI  - Large drinks are no mistake: glass size, not shape, affects alcoholic beverage
      drink pours.
AB  - INTRODUCTION AND AIMS: Alcohol content in drinks has been shown to be variable.
      This study evaluates claims regarding the effects of glass size and glass shape
      on the amount of alcohol served in on-premise drinks. DESIGN AND METHODS: Wine
      and spirits drinks were purchased and measured in 80 on-premise establishments in
      10 Northern California Counties. Alcohol content was measured as the liquid
      volume of the drink multiplied by the percentage alcohol by volume of given
      brands or from analysis of mixed drink and wine samples. RESULTS: Spirits drinks
      were classified as either straight shots or mixed drinks. Mixed drinks poured in
      short wide glasses were not found to contain more alcohol than those poured in
      tall thin glasses. Straight shots and mixed drinks served in the relatively large
      pint glass and variable 'other' glass type were found to contain more alcohol
      than drinks served in a short wide glass. No other significant differences were
      found between glass types. Analyses of establishment characteristics found that
      bars with mostly black patrons serve spirits drinks with more alcohol than bars
      with other patron types. DISCUSSION AND CONCLUSIONS: Glass shape does not affect
      actual drink pours in the USA but glass size does in some cases. Consumer
      education programs should foster awareness of the relatively high alcohol content
      of on-premise wine and mixed spirits drinks. More research is needed to evaluate
      potential differences in drink pours by patron race and ethnicity.

PMID- 19594791
TI  - Client-reported reasons for non-engagement in drug and alcohol treatment.
AB  - INTRODUCTION AND AIMS: To examine client-reported reasons for missed early
      appointments at a drug and alcohol treatment service and to compare
      characteristics of those who missed appointments with those who attended. DESIGN
      AND METHODS: Clients who missed a first or second appointment between 1 May and
      31 August 2007 at a public community-based outpatient treatment facility were
      invited to participate in a semistructured telephone interview. This consisted of
      an open-ended question asking the reason(s) for nonattendance, followed by a
      questionnaire of items for therapeutic alliance and service satisfaction,
      perceived impact of substance use and previous treatment experience, mostly rated
      on Likert scales. Database information on demographic and clinical variables was
      gathered for all clients who were accepted for treatment within the study time
      frame. Characteristics of those who missed a first or second appointment (n = 66)
      were compared with those who attended at least their first two appointments (n =
      97). RESULTS: Of clients who missed their appointments, 80.6% provided reasons
      for nonattendance, which included extraneous factors (50.0%), service
      shortcomings (29.7%), no further need for service (16.2%) and motivational
      ambivalence (4.1%). They generally had high ratings of therapeutic alliance and
      service satisfaction and identified their substance use as having a negative
      impact on their lives. Clients who missed appointments were more likely to be
      male, unmarried and have a history of polysubstance use. DISCUSSION AND
      CONCLUSIONS: Extraneous issues relating to the client may be a dominant obstacle
      in early treatment engagement. Efforts to overcome these issues may therefore
      improve early engagement.

PMID- 19594790
TI  - Predictors of 3-month retention in a drug treatment therapeutic community.
AB  - INTRODUCTION AND AIMS: To study rates of 3-month retention in a drug treatment
      therapeutic community and the characteristics of residents who remain in
      treatment. DESIGN AND METHODS: A total of 200 consecutive admissions to a
      therapeutic community in Christchurch, New Zealand received a structured
      interview and questionnaires and were prospectively followed for 3 months.
      Assessments included the Modified Mini-International Neuropsychiatric Interview
      (MINI), Hopkins Symptom Checklist (SCL-90), Temperament Character Inventory (TCI)
      and Short Form Health Survey (SF-36). RESULTS: A total of 107 out of 187
      residents remained in the program for at least 3 months. These residents had a
      better baseline mental health score (SF-36), higher lifetime depression, higher
      current sedative/hypnotic dependence and less lifetime stimulant dependence. The
      differences were modest and predicted around 18% of the variance in outcome.
      DISCUSSION AND CONCLUSIONS: The retention rate is consistent with other studies.
      Few variables predict those who discontinue treatment supporting a non
      discriminatory approach to new residents by clinicians.

PMID- 19594792
TI  - Drugs and Psychosis Project: a multi-centre European study on comorbidity.
AB  - INTRODUCTION AND AIMS: This paper describes the sociodemographic characteristics
      of 196 psychotic patients admitted to acute psychiatric wards in the UK, Denmark,
      Germany and Italy, with the aim of comparing comorbid with non-comorbid patients.
      DESIGN AND METHODS: It is a prospective field study with repeated measures at 1,
      6 and 12 months. Patients were recruited from acute psychiatric wards in four
      European centres. They were grouped as comorbid or not on the basis of urine
      analysis. The Schedules for Clinical Assessment in Neuropsychiatry was used to
      provide a psychiatric diagnosis, and the Positive and Negative Symptom Severity
      Scale for further information on specific symptoms with results from the
      Fragerstrom test for nicotine dependence also reported. RESULTS: Comorbid
      patients were younger than those who were not but did not differ significantly in
      the other sociodemographic measures. Differences in sociodemographic
      characteristics of patients between centres were apparent. Comorbid patients had
      higher levels of positive and lower levels of negative symptoms than those who
      were non-comorbid. Differences were found in the patterns of drug use between
      comorbid patients who were using cannabis compared with those who were not.
      DISCUSSION AND CONCLUSIONS: Cross-cultural differences in the sociodemographic
      characteristics of the comorbid patient population give us a better insight into
      this heterogenous group.

PMID- 19594793
TI  - Fluctuations in male ischaemic heart disease mortality in Russia 1959-1998:
      assessing the importance of alcohol.
AB  - INTRODUCTION AND AIMS: The decline in cardiovascular mortality in Russia
      following the Soviet anti-alcohol campaign of 1985-1988 and the subsequent
      increase when these extreme alcohol controls were repealed suggested that alcohol
      consumption is responsible for a substantial number of ischaemic heart disease
      (IHD) deaths in Russia. To examine whether a similar conclusion can be drawn on
      the basis of a time-series analysis covering a longer time period, namely 1959
      1998. DESIGN AND METHODS: Using ARIMA time-series analysis, the male IHD
      mortality rates from 1959 to 1998 were analysed in relation to three indicators
      of alcohol consumption: estimated per capita consumption, mortality from liver
      cirrhosis and alcohol poisonings. Cigarette sales and lung cancer mortality were
      used as indicators of smoking. RESULTS: Each indicator of alcohol consumption had
      positive and statistically significant relationships with male IHD mortality in
      bivariate autoregressive integrated moving average models. The association was
      stronger in models predicting changes in premature male IHD mortality (30-54
      years). At least one alcohol indicator was significantly related to IHD mortality
      in multivariate models, and in the case of premature IHD mortality, both
      mortality indicators were significant. DISCUSSION AND CONCLUSIONS: The results
      provide additional empirical evidence supporting alcohol's conceivable negative
      effects on IHD in Russia and the idea that binge drinking could be the mechanism
      through which this effect is mediated. There were no signs of any protective
      effects from alcohol among Russian men.

PMID- 19594794
TI  - Alcohol-related mortality in Ukraine.
AB  - INTRODUCTION AND AIMS: To substantiate public health policies aimed at
      diminishing alcohol-related harm, the level of alcohol-related deaths needs to be
      documented on a national level. The aim of this study was to explore the
      opportunities provided by the 1985-1988 anti-alcohol campaign related data for
      estimation of alcohol-related mortality in Ukraine. DESIGN AND METHODS:
      Ecological study design based on the aggregate-level data analysis regarding the
      natural experiment in Ukraine. All-cause and cause-specific observed mortality
      levels in 1986-88 compared to the extrapolated 1980-84 trends. The number and
      proportion of 'prevented' deaths were calculated for those causes, for which were
      observed: (1) reduction of mortality levels during the campaign and (2) increase
      after 1988. Alcohol-attributable fractions of mortality per one litre of per
      capita consumption were calculated for each death cause based on prevented deaths
      and consumption decrease estimates. The total number of alcohol-related deaths
      for a specific year was also calculated. RESULTS: Ukraine experienced a large
      mortality reduction during the campaign. The estimates of prevented deaths
      revealed that at least 76% of the mortality reduction was attributable to
      alcohol. Alcohol-related mortality due to injuries is much higher for men, while
      coronary heart disease (CHD) alcohol-attributable fractions were about 0.5 in
      middle age both for men and women. DISCUSSION AND CONCLUSIONS: While in Western
      countries alcohol is considered as a protective factor for CHD, in Ukraine
      alcohol-related cardiovascular mortality is rather high. In 2004 in Ukraine total
      number of alcohol-related deaths was about 119,000 or 251 per 100,000 of
      population.

PMID- 19594796
TI  - A review of drug prevention system development in Romania and its impact on youth
      drug consumption trends, 1995-2005.
AB  - ISSUES: A tremendous growth occurred in the reported drug use and abuse in
      Romania from 1995 to 1999. Lack of concern by government and little policy
      attention contributed to the surprising delay of drug policy and drug prevention
      system development. General public stigmatize drug users and drug consumption is
      considered a matter of personal fault and responsibility. There is some but not
      sufficient research and evaluation on drug use, abuse problem. APPROACH: Drug
      use, abuse and prevention are discussed from research-based, user-focused and
      prevention system development perspectives. Prevalence and trends of drug use,
      abuse in the past decade (1995-2005) are summarized. Prevention issues are
      discussed based on research data from adolescents, parents and teachers. The
      Romanian primary drug prevention system has been evaluated based on our
      experiences in drug use prevention activities carried out in schools and
      recreational environments. KEY FINDINGS: Public and scientific perspectives on
      drug consumption in Romania, between 1995 and 1999, were dominated by an
      idealistic, non-realistic perception. Since 1995, drug use among adolescents
      increased almost four times in less than 4 years. The first law against drug
      traffic and consumption was issued only in 2000. Now primary drug prevention
      strategies are in action, but in general they are lacking standard evaluation
      procedures. IMPLICATIONS/CONCLUSION: Conclusions are drafted for new perspectives
      in prevention activities. More long-term, user-focused, demand-centred prevention
      activities should be carried out in more and more diversified settings and
      evaluation should be thoroughly considered.

PMID- 19594795
TI  - From the brain to bad behaviour and back again: neurocognitive and
      psychobiological mechanisms of driving while impaired by alcohol.
AB  - ISSUES: Driving while impaired by alcohol (DWI) is responsible for substantial
      mortality and injury. Significant gaps in our understanding of DWI re-offending,
      or recidivism, reduce our ability to practically assess recidivism probability
      and to match interventions to individual risk profiles. These shortcomings
      reflect the baffling heterogeneity in the DWI population and the limited focus of
      much existing DWI recidivism research to psychosocial, psychological and
      substance use correlates. APPROACH: This narrative review summarises the evidence
      for the contribution of neurocognitive and psychobiological mechanisms to DWI
      behaviour and recidivism. Given the nascent nature of this literature, insight
      into the putative contribution of these mechanisms to DWI is also drawn from
      other experimental literatures, particularly those on alcohol use disorders and
      cognitive and behavioural neuroscience. KEY FINDINGS: Alcohol-related
      neurotoxicity and dysregulation of hypothalamic-pituitary-adrenal axis and
      serotonergic systems may underlie certain offender characteristics consistently
      correlated with heightened DWI risk, persistence and intervention resistance.
      Their markers are less vulnerable to sources of bias than subjective psychosocial
      indices and are more far-reaching than alcohol abuse in explaining DWI behaviour
      and recidivism. Implications. The investigation of neurocognitive and
      psychobiological mechanisms in DWI research is a promising avenue for discerning
      clinically meaningful subgroups within the DWI population. This can lead to
      research and development in alternative assessment and more targeted intervention
      technologies. CONCLUSION: Multidimensional research in DWI and recidivism offers
      novel avenues for increasing road safety.

PMID- 19594797
TI  - Warnings on alcohol containers and advertisements: international experience and
      evidence on effects.
AB  - ISSUES: In light of possible introduction of alcohol warning labels in Australia
      and New Zealand, this paper discusses the international experience with and
      evidence of effects of alcohol warning labels. APPROACH: The report describes
      international experience with providing information and warnings concerning the
      promotion or sale of alcoholic beverages, and considers the evidence on the
      effects of such information and warnings. The experience with and evaluations of
      the effects of tobacco warning labels are also considered. KEY FINDINGS: The most
      methodologically sound evaluations of alcohol warning labels are based on the US
      experience. Although these evaluations find little evidence that the introduction
      of the warning label in the USA had an impact on drinking behaviour, there is
      evidence that they led to an increase in awareness of the message they contained.
      In contrast, evaluations of tobacco warning labels find clear evidence of effects
      on behaviour. IMPLICATIONS: There is a need and opportunity for a rigorous
      evaluation of the impacts of introducing alcohol warning labels to add to the
      published work on their effectiveness. The experience with tobacco labels might
      guide the way for more effective alcohol warning labels. CONCLUSION: Alcohol
      warning labels are an increasingly popular alcohol policy initiative. It is clear
      that warning labels can be ineffective, but the tobacco experience suggests that
      effective warning labels are possible. Any introduction of alcohol warning labels
      should be evaluated in terms of effects on attitudes and behaviour.

PMID- 19594798
TI  - Hepatitis C treatment in pharmacotherapy services: increasing treatment uptake
      needs a critical view.
AB  - ISSUES: In an effort to increase the number of people undergoing hepatitis C
      treatment, a range of initiatives are planned or underway to provide treatment in
      non-specialist services, such as opioid pharmacotherapy treatment (OPT) clinics.
      APPROACH: This commentary considers the implications of this new approach to
      treatment delivery, taking account of individual-level issues generally discussed
      in the literature, such as knowledge of treatment and concerns about side
      effects. In addition, because less visible organisational and structural factors
      would equally influence the successful implementation of hepatitis C treatment in
      OPT services, these are also explored. KEY FINDINGS: Provision of hepatitis C
      treatment in OPT services raises a broad range of pressing questions, from
      individual knowledge and concern about treatment, to workforce issues, such as
      discrimination, and tensions between the need for supportive care during
      hepatitis C treatment and the surveillant, regulatory nature of OPT clinic
      operations. IMPLICATIONS: A thorough critical examination of the structure and
      delivery of all services involved is necessary. Social research can play a unique
      role in this assessment because of its ability to generate detailed insights into
      lived experience and make use of social theories that allow previously invisible
      operations of power to become visible. CONCLUSION: The success of hepatitis C
      treatment in new sectors, such as OPT clinics, is not a given. Close attention
      needs to be paid to the context and culture in which OPT is delivered. In turn,
      this needs to be considered alongside the context and culture necessary for
      successful hepatitis C treatment delivery.

PMID- 19594799
TI  - A healthy dose of scepticism: four good reasons to think again about protective
      effects of alcohol on coronary heart disease.
AB  - ISSUES: Alcohol has been implicated in both the popular press and scientific
      literature as having a protective effect for at least a dozen conditions
      including coronary heart disease (CHD). APPROACH: Epidemiological evidence for an
      apparent protective effect of alcohol on CHD is now being challenged on a number
      of fronts. This paper is a synopsis of those various challenges as they currently
      stand. KEY FINDINGS: The argument that systematic misclassification of ex
      drinkers and occasional drinkers to 'abstainer' categories among epidemiological
      studies might explain apparent protective effects of moderate alcohol consumption
      on CHD has recently been supported by new meta-analyses and independent research.
      The influence of uncontrolled or unknown factors on the relationship between
      alcohol and disease cannot be ruled out. Exclusion of participants on the basis
      of ill-health severely reduces study sample size and new analyses suggest that
      doing so might artificially create the appearance of protective effects. The
      ability of respondents to accurately recall their own alcohol consumption is in
      serious doubt and very few individuals maintain one single drinking level or
      style throughout life. The relationship between alcohol and some conditions might
      be a function of drinking patterns but few studies have addressed the issue.
      IMPLICATIONS: Popular perceptions regarding the strength of evidence for
      alcohol's protective effect on a growing number of conditions might be misguided.
      CONCLUSION: It is time for the wider research, health and medical community to
      seriously reflect on the quality of current evidence for apparent protective
      effects of alcohol on human disease.

PMID- 19594800
TI  - Australian superannuation funds and tobacco investments: issues for DAR readers.

PMID- 19594801
TI  - Prevalence rates and risk factors for hepatitis C among drug users not in
      treatment in Malaysia.
AB  - INTRODUCTION AND AIMS: The prevalence of hepatitis C virus (HCV) among heroin
      dependants in treatment was estimated at 89.9%; however, virtually no information
      exists on the prevalence or risk behaviour among the larger population of drug
      users not in treatment. This study assessed the prevalence of HCV and associated
      risk factors among this group with a view to designing more effective
      intervention programs. DESIGN AND METHODS: A cross-sectional survey of 552 not-in
      treatment drug users recruited from five key urban centres across peninsular
      Malaysia with on-site serological testing for HCV and HIV seropositivity was
      conducted. RESULTS: HCV prevalence was 65.4% for the overall sample, but higher
      among injecting drug users (67.1%) relative to non-injecting drug users (30.8%).
      Bivariate analysis suggested seven risk factors though only sharing injecting
      paraphernalia and lifetime homosexual/bisexual behaviour remained significant in
      multivariate analysis. DISCUSSION AND CONCLUSIONS: With the majority (65.9%)
      sharing injecting equipment and about the same proportion (65.4%) being HCV
      positive, the risk of further transmission to new drug users is high. It is
      imperative that the nascent needle and syringe exchange and condom distribution
      program and its ancillary services--launched in 2005 to fight HIV--be fine tuned,
      as a first step, to control HCV. With its greater infectivity and non-symptomatic
      character, HCV is more insidious. Given the shared risk factors of HCV and HIV,
      routine screening of drug users for HCV--currently non-existent--should be
      instituted. This, with other intervention measures, will help detect and control
      HCV at an earlier stage while also checking the spread of HIV.

PMID- 19594811
TI  - Hand-held echocardiogram does not aid in triaging chest pain patients from the
      emergency department.
AB  - BACKGROUND: Accurate triage of emergency department (ED) patients presenting with
      chest pain is a primary goal of the ED physician. In addition to standard
      clinical history and examination, a hand-held echocardiogram (HHE) may aid the
      emergency physician in making correct decisions. We tested the hypothesis that an
      HHE performed and interpreted by a cardiology fellow could help risk-stratify
      patients presenting to the ED with chest pain. METHODS: ED physicians evaluated
      36 patients presenting with cardiovascular symptoms. Patients were then
      dispositioned to either an intensive care bed, a monitored bed, an unmonitored
      bed, or home. Following disposition, an HHE was performed and interpreted by a
      cardiology fellow to evaluate for cardiac function and pathology. The outcomes
      evaluated (1) a change in the level of care and (2) additional testing ordered as
      a result of the HHE. RESULTS: The HHE showed wall motion abnormalities in 31% (11
      out of 36) of the studies, but the level of care did not change after HHE for any
      patients who presented with chest pain to the ED. No additional laboratory or
      imaging tests were ordered for any patients based on the results of the HHE.
      Eighty-six percent (31 out of 36) of the studies were of adequate quality for
      interpretation, and 32 out of 36 (89%) interpretations correlated with an
      attending overread. CONCLUSION: Despite the high prevalence of abnormal wall
      motion in this population, hand-held echocardiography performed in this ED
      setting did not aid in the risk stratification process of chest pain patients.

PMID- 19594812
TI  - Comparison of LVEF obtained with single-plane RAO ventriculography and
      echocardiography in patients with and without obstructive coronary artery
      disease.
AB  - The left ventricular ejection fraction (LVEF) determined by invasive
      ventriculography (routine cardiac cath; LV-gram) was compared with that
      determined by echocardiography in 100 patients scheduled for angiography (86% had
      LV-gram and 2DE during same hospital admission). Seventy percent of patients had
      at least single-vessel obstructive coronary artery disease, defined as more than
      50% stenosis. By all estimates, the LVEF was higher in patients without coronary
      artery disease (CAD) compared to patients with CAD. There was an excellent
      correlation between the LVEF by cath and echo, but this correlation was
      noticeably less strong in patients with CAD, especially with involvement of the
      left circumflex artery.

PMID- 19594813
TI  - Pulsed-wave tissue Doppler and color tissue Doppler echocardiography: calibration
      with M-mode, agreement, and reproducibility in a clinical setting.
AB  - BACKGROUND: Myocardial velocities can be measured with both pulsed-wave tissue
      Doppler (PWTD) and color tissue Doppler (CTD) echocardiography. We aimed to (A)
      to explore which of the two methods better approximates true tissue motion and
      (B) to examine the agreement and the reproducibility of the two methods in a
      routine clinical setting. METHODS: For Study A, the displacements of 63 basal
      myocardial segments from 13 patients were examined with M-mode and compared with
      the velocity-time integral of PWTD and CTD velocities. For Study B, the basal
      lateral segments from 58 patients were examined with PWTD and CTD, and the peak
      myocardial velocities during systole (Sm), early diastole (Em), and late diastole
      (Am) were measured. RESULTS: Study A: CTD-based measurements of displacement were
      12% lower than M-mode measurements (95% CI: -18%; -6%). PWTD velocity-time
      integrals measured at the outer edge of the spectral band were 40% higher (33%;
      46%) than M-mode measurements. Study B: PWTD measurements of myocardial velocity
      were systematically higher than CTD measurements: Sm 7.51 versus 5.54, difference
      1.97 +/- 1.41 cm/sec; Em 8.74 versus 6.86, difference 1.88 +/- 1.70 cm/sec; Am
      7.46 versus 5.17, difference 2.29 +/- 1.82 cm/sec; P < 0.001 for all.
      Intraobserver coefficient of variation for Sm, Em, and Am were 6%, 12%, and 12%
      for PWTD, 14%, 13%, and 20% for CTD. CONCLUSIONS: CTD measures numerically
      smaller tissue velocities than PWTD, mostly due to an overestimation of true
      tissue motion by PWTD. The methods have good agreement and comparable
      reproducibility.

PMID- 19594814
TI  - Impaired myocardial function in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) parameters of peak myocardial velocities
      (S', E', and A') has been employed to assess the regional left ventricular
      myocardial function. The global function index (GFI) derived from TDI has been
      recently employed to distinguish the different etiologies of left ventricular
      hypertrophy. OBJECTIVE: To analyze whether the GFI or individual TDI parameters
      of peak myocardial velocities (S', E', and A') allows detecting different degrees
      of regional myocardial dysfunction in the most frequent forms of hypertrophic
      cardiomyopathy (HCM). METHODS: GFI = (E/E')/S' (where E is the peak transmitral
      flow velocity, E' is the early diastolic myocardial velocity, and S' is the peak
      systolic myocardial velocity) and TDI peak myocardial velocities was measured in
      the septal and lateral mitral annulus in 101 patients with HCM (mean age 47.5 +/-
      14 years, 58 women) and in age-matched group of 30 healthy controls (mean age 46
      +/- 6 years, 16 women). RESULTS: Forty-five patients had nonobstructive
      asymmetric septal HCM, 20 patients had a subaortic gradient >or= 30 mm Hg, 21 p.
      had apical HCM, and 15 p. had other forms of HCM (midventricular, symmetric, and
      biventricular). All patients with HCM exhibited a decrease in early diastolic
      (E') and systolic (S') myocardial velocities, both in the lateral and septal
      mitral annulus border, but more pronounced in septal-mitral annulus. Septal GFI
      was higher in HCM patients than in healthy subjects (1.8 (1.1-2.5) and (0.57
      (0.31-0.92), respectively, P < 0.001), but no differences were seen when
      different forms of HCM were compared. CONCLUSIONS: In a selected population of
      patients with HCM and a preserved left ventricular(LV) systolic function, GFI and
      individual TDI parameters of peak velocity (S', E', and A') and E/E' ratio were
      similar in different forms of HCM, indicating that in all patients with HCM there
      is regional systolic and diastolic myocardial dysfunction, regardless of the
      location of hypertrophy.

PMID- 19594815
TI  - Integrating research into clinical practice: development of an echocardiography
      research unit.
AB  - Introducing a research program into an echocardiography clinical practice can
      pose many challenges. Some initial factors to consider are the possible effects
      on the current clinical schedule and the equipment and personnel resources
      required to support the research projects. More importantly, how can an
      organization successfully complete reliable and accurate research projects? Here,
      we describe our experience with establishing an echocardiography research center
      within our clinical echocardiography practice. In addition, we identify key staff
      roles, highlight our current research practice methods, and suggest essential
      components that may prove advantageous when incorporating echocardiography
      research into a clinical practice.

PMID- 19594817
TI  - Severe mitral and aortic regurgitation in association with ankylosing
      spondylitis.
AB  - Aortic disease and aortic valve regurgitation are well documented in association
      with ankylosing spondylitis, although involvement of the mitral valve occurs more
      rarely. We report a case of severe mitral and aortic regurgitation in association
      with ankylosing spondylitis. We then discuss the characteristic cardiac
      manifestations that may occur in association with ankylosing spondylitis and the
      associated echocardiographic features.

PMID- 19594818
TI  - New echocardiographic techniques in the evaluation of left ventricular mechanics
      in subclinical thyroid dysfunction.
AB  - The new echocardiographic techniques for the study of physiopathological
      intramyocardial phenomena include video densitometry (VD), integrated backscatter
      (IBS), and color Doppler myocardial imaging (CDMI). Being more independent from
      cardiac load and from rotational and translational heart motion, these new
      sensible, noninvasive techniques such as CDMI and IBS show a real incremental
      value in comparison with conventional echocardiography and allow to detect subtle
      functional and textural abnormalities of intramural myocardium, partially
      undetectable by conventional two-dimensional Doppler echocardiography.
      Subclinical thyroid dysfunction (STD), both in its hypo- and hyperthyroidism
      form, has a relatively high prevalence in general population (9-15% with a lower
      percentage of adult males), hence it could be very useful to study more deeply
      heart involvement in these physiopathological conditions and understand the
      complex relationship between thyroid and heart. The use of these new ultrasonic
      techniques in subclinical hypothyroidism helps to detect the early simultaneous
      involvement of both cardiac cycle phases, which causes a decrease of
      intramyocardial contractility and an impairment of both active and passive phases
      of diastole. In subclinical hyperthyroidism, these new ultrasonic techniques
      permitted to discover more complex and different early cardiac abnormalities of
      both systolic and diastolic phases.

PMID- 19594819
TI  - Biphasic pulmonary regurgitation.
AB  - A patient with first-degree atrioventricular (AV) block and pulmonary
      regurgitation underwent a transthoracic echocardiogram. Continuous wave Doppler
      interrogation of the pulmonic valve displayed a biphasic regurgitation pattern. A
      discussion of the potential mechanism underlying this pattern is presented.

PMID- 19594820
TI  - Echocardiographic manifestations of complications of radiation therapy.
AB  - Radiation therapy may affect all of the layers of the heart (epicardial arteries,
      pericardium, valves, and myocardium). This is especially true after mediastinal
      or breast irradiation. Coronary artery disease, with resultant myocardial
      infarction, is the most common cause of death. We present a patient who developed
      typical constrictive pericarditis as well as valve lesions typical of radiation
      toxicity (the mitral valve leaflets were thickened at their bases, with the tips
      spared). The pericardial constriction was manifested by all of the typical echo
      Doppler findings, namely septal bounce, dilated inferior vena cava, significant
      respiratory drop in inspiratory mitral E velocity with a normal tissue Doppler
      e', and expiratory reversal of flow into the hepatic veins.

PMID- 19594821
TI  - Mycotic ascending aortic pseudoaneurysm causing a large mediastinal abscess.
AB  - Mycotic aneurysm is a rare, life-threatening condition with high mortality rates
      and challenging diagnosis. A 46-year-old man, with a history of subaortic
      membranectomy, was admitted with a new onset fever and dyspnea. Transesophageal
      echocardiography and computed tomography demonstrated a mycotic pseudoaneurysm of
      the ascending aorta and mediastinal abscess due to aneurysm rupture. The patient
      fully recovered after an immediate diagnose and urgent surgery.

PMID- 19594822
TI  - Blood cyst of the mitral valve: a rare cause of stroke.
AB  - Intracardiac blood cysts are thin-walled cysts, lined by flattened, cobblestone
      shaped epithelium, and filled with nonorganized blood. During autopsy, they are
      found on cardiac valves in approximately 50% of infants below the age of 2 months
      and are rarely found after the age of 2 years. We report a rare case of blood
      cyst attached to the mitral valve and a possible cause of an embolic stroke.

PMID- 19594824
TI  - A fellow's perspective on handheld echo during cardiology rounds: "Me and Charlie
      Down by the bedside".

PMID- 19594823
TI  - Embolization of atrial septal occluder device into the pulmonary artery: a rare
      complication and usefulness of live/real time three-dimensional transthoracic
      echocardiography.
AB  - Percutaneous closure of atrial septal defects (ASD) in adults has emerged as an
      alternative to surgery. We report a rare complication of an atrial septal
      occluder device embolization into the pulmonary artery which was detected by
      fluoroscopy and echocardiography. The potential usefulness of live/real time
      three-dimensional transthoracic echocardiography in the management of patients
      undergoing percutaneous ASD occlusion is described.

PMID- 19594825
TI  - Caseous calcification of the mitral annulus imaged with 64-slice multidetector
      CT.

PMID- 19594826
TI  - Real time three-dimensional transesophageal echocardiography for guiding
      percutaneous mitral valvuloplasty.

PMID- 19594827
TI  - Embolization of atrial septal occluder device into the pulmonary circulation:
      role of transesophageal echocardiography.

PMID- 19594828
TI  - The complete mitochondrial genome of the yeast Pichia sorbitophila.
AB  - Here, we report the complete nucleotide sequence of the 39 107-bp mitochondrial
      genome of the yeast Pichia sorbitophila. This genome is closely related to those
      of Candida parapsilosis and Debaryomyces hansenii, as judged from sequence
      similarities and synteny conservation. It encodes three subunits of cytochrome
      oxidase (COX1, COX2 and COX3), three subunits of ATP synthase (ATP6, ATP8 and
      ATP9), the seven subunits of NADH dehydrogenase (NAD1-6 and NAD4L), the
      apocytochrome b (COB), the large and small rRNAs and a complete set of tRNAs.
      Although the mitochondrial genome of P. sorbitophila contains the same core of
      mitochondrial genes observed in the ascomycetous yeasts, those coding for the
      RNAse P and the ribosomal protein VAR1p are missing. Moreover, the mtDNA of P.
      sorbitophila contains several introns in its genes and has the particularity of
      possessing an intron, which is not linked to any upstream exon.

PMID- 19594829
TI  - Male-specific expression of Sox9 during gonad development of crocodile and mouse
      is mediated by alternative splicing of its proline-glutamine-alanine rich domain.
AB  - The initial trigger for sexual differentiation is regulated by multiple ways
      during embryonic development. In vertebrates, chromosome-based mechanisms
      generally known as genetic sex determination are prevalent; however, some
      species, such as many reptilians, display temperature-dependent sex
      determination. The Sry-related transcription factor, Sox9, which is expressed by
      an evolutionary conserved gene, has been shown to be a key player in the process
      of sex determination. In the present study, we report the identification and
      expression of crocodile homolog of Sox9 (cpSox9) from the Indian Mugger,
      Crocodylus palustris. We show that cpSox9 undergoes extensive alternative
      splicing around the proline-glutamine-alanine rich transactivation domain that
      results in cpSox9 variants with presumably impaired or reduced transactivation
      potential. The multiple isoforms were also detected in various embryonic tissues,
      with some of them displaying a differential expression profile. With respect to
      sex differentiation, a putative unspliced full-length cpSox9 could be detected
      only in the genital ridge-adrenal-mesonephros complex of male, but not female
      embryos during the temperature-sensitive period. Importantly, we further show
      that this phenomenon was not restricted to the temperature-dependent sex
      determination species C. palustris, but was also observed in the mouse, a species
      exhibiting genetic sex determination. Thus, the present study describes, for the
      first time, a complete coding locus of Sox9 homolog from a temperature-dependent
      sex determination species. More importantly, we demonstrate an evolutionarily
      conserved role of alternative splicing resulting in transcriptional diversity and
      male-sex specific expression of Sox9 during testis development in vertebrates
      (i.e. irrespective of their underlying sex-determination mechanisms).

PMID- 19594830
TI  - A unique lipoylation system in the Archaea. Lipoylation in Thermoplasma
      acidophilum requires two proteins.
AB  - Members of the 2-oxoacid dehydrogenase multienzyme complex family play a key role
      in the pathways of central metabolism. Post-translational lipoylation of the
      dihydrolipoyl acyltransferase component of these complexes is essential for their
      activity, the lipoyllysine moiety performing the transfer of substrates and
      intermediates between the different active sites within these multienzyme
      systems. We have previously shown that the thermophilic archaeon, Thermoplasma
      acidophilum, has a four-gene cluster encoding the components of such a complex,
      which, when recombinantly expressed in Escherichia coli, can be assembled into an
      active multienzyme in vitro. Crucially, the E. coli host carries out the required
      lipoylation of the archaeal dihydrolipoyl acyltransferase component. Because
      active 2-oxoacid dehydrogenase multienzyme complexes have never been detected in
      any archaeon, the question arises as to whether Archaea possess a functional
      lipoylation system. In this study, we report the cloning and heterologous
      expression of two genes from Tp. acidophilum whose protein products together show
      significant sequence identity with the single lipoate protein ligase enzyme of
      bacteria. We demonstrate that both recombinantly expressed Tp. acidophilum
      proteins are required for lipoylation of the acyltransferase, and that the two
      proteins associate together to carry out this post-translational modification.
      From the published DNA sequences, we suggest the presence of functional
      transcriptional and translational regulatory elements, and furthermore we present
      preliminary evidence that lipoylation occurs in vivo in Tp. acidophilum. This is
      the first report of the lipoylation machinery in the Archaea, which is unique in
      that the catalytic activity is dependent on two separate gene products.

PMID- 19594832
TI  - Protein oligomerization induced by oleic acid at the solid-liquid interface-
      equine lysozyme cytotoxic complexes.
AB  - Protein oligomeric complexes have emerged as a major target of current research
      because of their key role in aggregation processes in living systems and in
      vitro. Hydrophobic and charged surfaces may favour the self-assembly process by
      recruiting proteins and modifying their interactions. We found that equine
      lysozyme assembles into multimeric complexes with oleic acid (ELOA) at the solid
      liquid interface within an ion-exchange chromatography column preconditioned with
      oleic acid. The properties of ELOA were characterized using NMR, spectroscopic
      methods and atomic force microscopy, and showed similarity with both amyloid
      oligomers and the complexes with oleic acid and its structural homologous protein
      alpha-lactalbumin, known as human alpha-lactalbumin made lethal for tumour cells
      (HAMLET). As determined by NMR diffusion measurements, ELOA may consist of 4-30
      lysozyme molecules. Each lysozyme molecule is able to bind 11-48 oleic acids in
      various preparations. Equine lysozyme acquired a partially unfolded conformation
      in ELOA, as evident from its ability to bind hydrophobic dye 8-anilinonaphthalene
      1-sulfonate. CD and NMR spectra. Similar to amyloid oligomers, ELOA also
      interacts with thioflavin-T dye, shows a spherical morphology, assembles into
      ring-shaped structures, as monitored by atomic force microscopy, and exerts a
      toxic effect in cells. Studies of well-populated ELOA shed light on the nature of
      the amyloid oligomers and HAMLET complexes, suggesting that they constitute one
      large family of cytotoxic proteinaceous species. The hydrophobic surfaces can be
      used profitably to produce complexes with very distinct properties compared to
      their precursor proteins.

PMID- 19594831
TI  - A novel ATP-binding cassette transporter is responsible for resistance to
      viologen herbicides in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The charged quaternary ammonium compounds--methyl, ethyl and benzyl viologens-
      generate reactive oxygen species in photosynthetic cells. Three independent
      methyl viologen-resistant spontaneous mutants of Synechocystis sp. PCC 6803 were
      identified, in which the conserved R115 residue of the Slr1174 protein was
      replaced with G115, L115 and C115. The Slr1174 protein of the DUF990 family is
      related to the permease subunit of an ABC-2-type transporter and its R115
      mutation was found to be solely responsible for the observed methyl viologen
      resistance. Bioinformatic analysis showed that in various bacterial genomes, two
      genes encoding another permease subunit and the ATPase component of an ATP
      binding cassette transporter form putative operons with slr1174 orthologs,
      suggesting that the protein products of these genes may form functional
      transporters. The corresponding genes in Synechocystis sp. PCC 6803, i.e. slr0610
      for the permease and slr1901 for the ATPase, did not form such an operon.
      However, insertional inactivation of any slr1174, slr0610 or slr1901 genes in
      both the wild-type and the R115-resistant mutant resulted in increased
      sensitivity to methyl, ethyl and benzyl viologens; moreover, single- and double
      insertion mutants did not differ in their viologen sensitivity. Our data suggest
      that Slr1901, Slr1174 and Slr0610 form a heteromeric ATP-binding cassette-type
      viologen exporter, in which each component is critical for viologen extrusion.
      Because the greatest increase in mutant sensitivity was observed in the case of
      ethyl viologen, the three proteins have been named EvrA (Slr1901), EvrB (Slr1174)
      and EvrC (Slr0610). This is the first report of a function for a DUF990 family
      protein.

PMID- 19594833
TI  - Anti-polymorphonuclear neutrophil antibodies in patients with leukopenia or
      neutropenia.
AB  - INTRODUCTION: Immune humoral neutropenia (Np) could be the consequence of anti
      polymorphonuclear neutrophil (PMN) antibodies, circulating immune complexes (CIC)
      and/or antibodies against myeloid precursors. Granulocyte immunofluorescence test
      (GIFT) and a leukoagglutination technique (LAGT) assays are recommended for its
      diagnosis. METHODS: Fifty adult patients with secondary Np were screened for anti
      PMN. GIFT by flow cytometry from viable PMN and LAGT were employed. In addition,
      CIC levels, low expression of CD16(b) (CD16 (b)(low)), PMN phenotype and sera
      tumor necrosis factor-alpha (TNF-alpha) were also evaluated. RESULTS: Direct IgG
      PMN binding (dir-GIFT) was positive in 16% of the patients. Antibodies against
      autologous PMN were detected in 32% of the samples by indirect (ind)-GIFT and
      demonstrated in 70% of the sera by both ind-GIFT and/or LAGT. Predominance of
      human neutrophil alloantigen (HNA)-1b and HNA-2 expression was confirmed.
      CD16(b)(low) was detected in 16% of the patient's PMN and TNF-alpha in 68% of
      sera patients. CONCLUSION: Our results suggest that diagnosis of immune Np in the
      laboratory may be improved by focusing on patient's PMN together with the
      assessment of cellular markers.

PMID- 19594834
TI  - Impaired spatial navigation in pediatric anxiety.
AB  - BACKGROUND: Previous theories implicate hippocampal dysfunction in anxiety
      disorders. Most of the data supporting these theories stem from animal research,
      particularly lesion studies. The generalization of findings from rodent models to
      human function is hampered by fundamental inter-species differences. The present
      work uses a task of spatial orientation, which is known to rely on hippocampal
      function. Deficits in spatial navigation in anxious children suggest that the
      hippocampal network involved in spatial orientation is also implicated in anxiety
      disorders. METHODS: Thirty-four treatment-naive children with an anxiety disorder
      (mean 11.00 years +/- 2.54) are compared to 35 healthy age- and IQ-matched
      healthy children (mean 11.95 years +/- 2.36) on a virtual, computer-based
      equivalent of the Morris Water Maze task. RESULTS: Results indicate that children
      with anxiety disorder exhibit overall impaired performance relative to the
      comparison group. Anxious children made more heading direction errors and had
      worse accuracy in completing trials relative to controls. CONCLUSIONS: The
      results present novel evidence that spatial orientation deficits occur in
      pediatric anxiety.

PMID- 19594835
TI  - A prospective study of toddlers with ASD: short-term diagnostic and cognitive
      outcomes.
AB  - BACKGROUND: Despite recent increases in the number of toddlers referred for a
      differential diagnosis of autism spectrum disorders (ASD), knowledge of short
      term stability of the early diagnosis as well as cognitive outcomes in this
      cohort is still limited. METHOD: Cognitive, social, and communication skills of
      89 clinic-referred toddlers were assessed at the average age of 21.5 (SD = 4.9)
      months, and reassessed at 46.9 (SD = 7.7) months. Groups with stable and unstable
      diagnostic presentation were identified and compared on their profile of
      cognitive and social-communicative skills obtained at the time of initial
      diagnosis. RESULTS: Stability of the ASD diagnosis was 100%; diagnosis of autism
      was stable in 74% of cases as compared to 83% and 81% in PDD-NOS and Non-ASD
      groups, respectively. Worsening of social disability symptoms resulting in autism
      diagnosis was noted in 17% of toddlers initially diagnosed with PDD-NOS and in
      19% of toddlers with initial diagnosis of non-ASD disorder. However, marked
      improvement was noted in approximately 1/4 of children initially presenting with
      autism, warranting diagnostic reassignment to PDD-NOS at follow-up. An analysis
      of developmental skills profiles suggests particular relevance of the assessment
      of verbal and nonverbal communication skills to diagnostic differentiation
      between subtypes within ASD in the second year of life. CONCLUSIONS: Stability of
      ASD diagnosis in toddlers is high, though marked changes in severity of symptoms
      is to be expected in a minority of cases. Simultaneous consideration of
      cognitive, social, and communication skills profiles enhances accuracy of
      diagnostic classification and prediction of outcome.

PMID- 19594836
TI  - Gene-environment interplay in internalizing disorders: consistent findings across
      six environmental risk factors.
AB  - BACKGROUND: Behavior genetic methods can help to elucidate gene-environment (G-E)
      interplay in the development of internalizing (INT) disorders (i.e., major
      depression and anxiety disorders). To date, however, no study has conducted a
      comprehensive analysis examining multiple environmental risk factors with the
      purpose of delineating general mechanisms of G-E influence in the development of
      INT disorders. METHODS: The sample consisted of 1315 male and female twin pairs
      participating in the age 17 assessment of the Minnesota Twin Family Study.
      Quantitative G-E interplay models were used to examine how genetic and
      environmental risk for INT disorders changes as a function of environmental
      context. Multiple measures and informants were employed to construct composite
      measures of INT disorders and six environmental risk factors including: stressful
      life events, mother-child and father-child relationship problems, antisocial and
      prosocial peer affiliation, and academic achievement and engagement. RESULTS:
      Significant moderation effects were detected between each environmental risk
      factor and INT such that in the context of greater environmental adversity,
      nonshared environmental factors became more important in the etiology of INT
      symptoms. CONCLUSION: Our results are consistent with the interpretation that
      environmental stressors have a causative effect on the emergence of INT
      disorders. The consistency of our results suggests a general mechanism of
      environmental influence on INT disorders regardless of the specific form of
      environmental risk.

PMID- 19594837
TI  - Psychological vulnerability in children next-born after stillbirth: a case
      control follow-up study.
AB  - BACKGROUND: Case studies and anecdotal accounts suggest that perinatal loss may
      impact upon other children in the family, including those born subsequent to
      loss. However, there is a dearth of systematically collected quantitative data on
      this potentially vulnerable group. METHODS: Case-controlled follow-up of 52
      mothers with history of stillbirth with their next-born children aged 6-8 years,
      and 51 control mother-child dyads. Previously reported baseline data included
      maternal antenatal and postnatal psychological assessment, and infant security of
      attachment at 12 months. Follow-up assessments included maternal psychiatric and
      socio-demographic data, mother and teacher-rated scales of the child's strengths
      and difficulties, child IQ, observer-rated mother-child interaction and maternal
      reports of child health. RESULTS: There were no significant between-group
      differences in child cognitive or health assessments, or in teacher-rated child
      difficulties. However, mothers with history of stillbirth (the index group)
      reported increased child difficulties, in particular peer problems, and more
      adverse interaction was observed in respect of higher levels of maternal
      criticism of the child's actions, more overall controlling behaviour by the
      mother, a less harmonious emotional atmosphere and a lower level of maternal
      engagement with the child. Some of these effects appeared to be mediated by
      maternal perinatal psychological symptoms and family breakdown. CONCLUSIONS: This
      study provides no evidence to suggest that siblings born after stillbirth are
      clinically at risk but does lend empirical support to clinical reports that such
      children are seen by their mothers as having problems and that they are exposed
      to less optimal interaction with their mothers. Possible interpretations of these
      findings are discussed in the context of theoretical accounts of 'replacement
      child' and 'vulnerable child' syndromes.

PMID- 19594839
TI  - The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease
      endpoints.
AB  - The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials
      Group (ACTG), the largest HIV clinical trials organization in the world. Its main
      objective is to investigate oral complications associated with HIV/AIDS as the
      epidemic is evolving, in particular, the effects of antiretrovirals on oral
      mucosal lesion development and associated fungal and viral pathogens. The OHARA
      infrastructure comprises: the Epidemiologic Research Unit (at the University of
      California San Francisco), the Medical Mycology Unit (at Case Western Reserve
      University) and the Virology/Specimen Banking Unit (at the University of North
      Carolina). The team includes dentists, physicians, virologists, mycologists,
      immunologists, epidemiologists and statisticians. Observational studies and
      clinical trials are being implemented at ACTG-affiliated sites in the US and
      resource-poor countries. Many studies have shared end-points, which include oral
      diseases known to be associated with HIV/AIDS measured by trained and calibrated
      ACTG study nurses. In preparation for future protocols, we have updated existing
      diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993.
      The proposed case definitions are designed to be used in large-scale
      epidemiologic studies and clinical trials, in both US and resource-poor settings,
      where diagnoses may be made by non-dental healthcare providers. The objective of
      this article is to present updated case definitions for HIV-related oral diseases
      that will be used to measure standardized clinical end-points in OHARA studies,
      and that can be used by any investigator outside of OHARA/ACTG conducting
      clinical research that pertains to these end-points.

PMID- 19594840
TI  - A clinico-pathologic study of 311 intra-oral salivary gland tumors in Thais.
AB  - BACKGROUND: There have been several epidemiologic studies on intra-oral salivary
      gland tumors in several countries, but little is known of these tumors in
      Thailand. OBJECTIVES: To determine the relative frequency and distribution of
      various types of intra-oral salivary gland tumors in the Thai population.
      METHODS: The files of the Department of Oral Pathology, Faculty of Dentistry,
      Chulalongkorn University, from 1969 to 2007 were searched for intra-oral salivary
      gland tumors. Histopathologic slides were reviewed and reclassified according to
      the 2005 WHO Classification of Head and Neck Tumors. The age, gender, race, and
      anatomical distribution of the tumors were collected from the patients' records.
      RESULTS: Of the 16,358 accessioned cases, 311 cases (1.90%) were diagnosed as
      intra-oral salivary gland tumors. One hundred and forty-seven cases (47.27%) were
      benign tumors, while 164 cases (52.73%) were malignant tumors. The mean age of
      the patient +/- SD = 41.57 +/- 16.65 years. Females outnumbered male patients by
      a ratio of M:F = 1:1.38. Almost all except one patient were Thais. Pleomorphic
      adenoma was the most common intra-oral salivary gland tumor. The majority of
      cases occurred at the palate. CONCLUSIONS: Pleomorphic adenoma is the most common
      intra-oral salivary gland tumor and the most common benign intra-oral salivary
      gland tumor, while mucoepidermoid carcinoma is the most common malignant intra
      oral salivary gland tumor. Intra-oral salivary gland tumors in Thailand elicit
      similar trend as in previous studies, with only minor differences such as the
      ranking of some tumors, the higher incidence of intra-bony location, and the
      lower incidence of polymorphous low-grade adenocarcinoma.

PMID- 19594841
TI  - Botulinum neurotoxin-A for treatment of refractory neck pain: a randomized,
      double-blind study.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of Botulinum neurotoxin-A
      (BoNT-A) in the patients with refractory neck pain. BACKGROUND: An analgesic
      effect is suggested for BoNT-A by a number of animal studies. Two blinded studies
      suggested efficacy of BoNT-A in a chronic neck pain. METHODS: Forty-seven
      subjects were enrolled in a prospective, double-blind, placebo-controlled study.
      A total of 150 to 300 units of BoNT-A were injected into the neck and shoulder
      muscles based on pain localization. Subjects completed the visual analog scale
      (VAS), Pain Frequency Questionnaire and the Modified Oswestry Pain Questionnaire
      (MOPQ) at baseline, 3 and 8 weeks after the treatment. The primary outcomes
      consisted of: 1) > or =50% improvement on the VAS; and 2) > or =30% reduction in
      pain day frequency. The secondary outcome was an improvement of ADL in MOPQ.
      Excellent responders (ERs) were those who met all three outcomes. RESULTS: At 2
      months, a significant reduction in the mean VAS (pain intensity) was noted in the
      BoNT-A group compared with the placebo (P = 0.0018, CI 95% from 2.51 to 7.89). At
      2 months, there were six ERs in the BoNT-A group and one ER in the placebo group
      (P = 0.0152). CONCLUSION: Administration of BoNT-A into the neck and shoulder
      muscles for treatment of chronic refractory neck pain met one of the two primary
      outcomes: reduction in pain intensity. More ERs were noted in the Botox group.

PMID- 19594843
TI  - Commentary: the paradox of analgesic medication elimination.

PMID- 19594842
TI  - A pilot study investigating the effects of fast left prefrontal rTMS on chronic
      neuropathic pain.
AB  - OBJECTIVE: Stimulating the human cortex using transcranial magnetic stimulation
      (TMS) temporarily reduces clinical and experimental pain; however, it is unclear
      which cortical targets are the most effective. The motor cortex has been a
      popular target for managing neuropathic pain, while the prefrontal cortex has
      been investigated for an array of nociceptive pain conditions. It is unclear
      whether the motor cortex is the only effective cortical target for managing
      neuropathic pain, and no published studies to date have investigated the effects
      of prefrontal stimulation on neuropathic pain. DESIGN: This preliminary pilot
      trial employed a sham-controlled, within-subject, crossover design to evaluate
      clinical pain as well as laboratory pain thresholds among four patients with
      chronic neuropathic pain. Each participant underwent three real and three sham 20
      minute sessions of 10 Hz left prefrontal repetitive TMS. Daily pain diaries were
      collected for 3 weeks before and after each treatment phase along with a battery
      of self-report pain and mood questionnaires. RESULTS: Time-series analysis at the
      individual patient level indicated that real TMS was associated with significant
      improvements in average daily pain in 3 of the 4 participants. These effects were
      independent of changes in mood in two of the participants. At the group level, a
      decrease of 19% in daily pain on average, pain at its worst, and pain at its
      least was observed while controlling for changes in mood, activity level and
      sleep. The effects of real TMS were significantly greater than sham. Real TMS was
      associated with increases in thermal and mechanical pain thresholds, whereas sham
      was not. No statistically significant effects were observed across the
      questionnaire data. CONCLUSIONS: The prefrontal cortex may be an important TMS
      cortical target for managing certain types of pain, including certain neuropathic
      pain syndromes.

PMID- 19594844
TI  - The prevalence and impact of chronic pain with neuropathic pain symptoms in the
      general population.
AB  - OBJECTIVE: We performed a prevalence estimate of chronic pain with neuropathic
      pain (NeP) symptoms to determine its frequency and associations with morbidity.
      DESIGN: We conducted a telephone-based survey based upon a random sampling of
      both urban and rural households of the general population in one Canadian
      province to determine NeP prevalence and its impact upon financial well-being and
      quality of life. OUTCOME MEASURES: Telephonic use of the DN4 questionnaire
      (DN4Q), used to identify NeP symptoms in those patients with chronic pain, was
      validated within selected clinical populations of chronic pain. Epidemiological
      data was obtained for all subjects. EuroQoL (EQ)-5D data estimating quality of
      life was measured. RESULTS: Chronic pain was present in 35.0% of the surveyed
      population of 1,207 subjects, with NeP symptoms present in 17.9%. The NeP group
      had significantly more pain, was female predominant, had a greater belief of
      being economically disadvantaged, suffered from more restrictions in mobility and
      in usual activities, and had overall lower EQ-5D utility scores compared with
      subjects with non-NeP. DN4Q validation demonstrated that pain entities not
      normally defined as NeP are recorded as such using the DN4Q, and that a spectrum
      of NeP features may occur across a host of painful conditions. CONCLUSION:
      Despite limitations of the DN4Q, symptoms of NeP may be more prevalent in the
      general population than expected and has a greater impact upon patients' lives
      than non-NeP. Limitations of the DN4Q may relate to the concept of a spectrum of
      NeP existent amongst heterogenous NeP and non-NeP syndromes.

PMID- 19594845
TI  - Do opioids induce hyperalgesia in humans? An evidence-based structured review.
AB  - DESIGN/OBJECTIVES: Consistent rodent evidence indicates that opioid exposure will
      decrease the rodent's pain threshold (ptr). This is termed opioids-induced
      hyperalgesia (OIH). Currently, the consistency of the evidence for the occurrence
      of OIH in humans is unclear. This is a structured evidence-based review for all
      levels of evidence (all studies and case reports) on OIH in humans in order to
      determine the consistency of this evidence. METHODS: Computer and manual
      literature searches yielded 504 OIH references (human and animal). Of these, 48
      remained after application of inclusion/exclusion criteria. These references
      addressed 10 hypotheses that the OIH literature has utilized to test for the
      possibility of OIH in humans. These are the following: opioid addicts maintained
      on opioids will have decreased ptr and/or tolerance; detoxifying opioid addicts
      from opioids will increase their ptr and/or tolerance; stopping, decreasing, or
      rotating to a different opioid or detoxifying from an opioid will improve pain
      and/or allodynia; chronic pain patients(CPPs) placed on opioids will develop
      decreased ptr and/or tolerance; CPPs on opioids will have decreased ptr and/or
      tolerance vs CPPs not on opioids; opioid infusion in normal volunteers or CPPs
      will decrease ptr and/or tolerance; former opioid addicts exposed to opioids will
      demonstrate a decrease in ptr and/or tolerance; opioid infusion in normal
      volunteers will increase secondary hyperalgesia as measured by allodynia or
      hyperalgesia; perioperative opioids will increase postoperative pain and/or
      opioid requirements; and placement on opioids postsurgery leads to progressive
      increased intake (acute tolerance). Each report was characterized by the type of
      study it represented according to the Agency for Health Care Policy and Research
      (AHCPR) guidelines and independently rated by two raters according to 14 quality
      criteria with a quality score calculated. For studies under each hypothesis, an
      average quality score and the percentage of studies supporting the hypothesis was
      calculated. Finally, for studies under each hypothesis, utilizing AHCPR criteria,
      a consistency rating was derived based on the percentage score of studies
      supporting the hypothesis. RESULTS: Two studies had quality scores below 65% and
      were not utilized. Overall, the strongest evidence (consistent, A) came from
      opioid infusion studies in normal volunteers as measured by secondary
      hyperalgesia. This evidence was supported by inconsistent evidence (C) from:
      studies addressing opioid infusions in normal volunteers or CPPs for decreasing
      ptr and/or tolerance; and studies addressing increases in postop opioid
      requirements or pain if peri-opioids were utilized. For the other seven
      hypotheses, there were too few studies to draw a conclusion or the evidence for
      the hypothesis were case reports or the results of the studies within the
      hypothesis were not interpretable. CONCLUSIONS: There is not sufficient evidence
      to support or refute the existence of OIH in humans except in the case of normal
      volunteers receiving opioid infusions. Prospective CPP clinical studies measuring
      ptrs and tolerances pre- and post-opioid placement with CPP non-opioid control
      groups are required.

PMID- 19594846
TI  - Documenting and improving opioid treatment: the Prescription Opioid Documentation
      and Surveillance (PODS) System.
AB  - OBJECTIVE: To demonstrate that a computer-assisted survey instrument offers an
      efficient means of patient evaluation when initiating opioid therapy. Design. We
      report on our experience with the Prescription Opioid Documentation and
      Surveillance (PODS) System, a medical informatics tool that uses validated
      questionnaires to collect comprehensive clinical and behavioral information from
      patients with chronic pain. SETTING AND PATIENTS: Over a 39-month period, 1,400
      patients entered data into PODS using a computer touch screen in a Veterans
      Administration Pain Clinic. MEASURES: Indices of pain intensity, function, mental
      health status, addiction history, and the potential for prescription opioid abuse
      were formatted for immediate inclusion into the medical record. RESULTS: The PODS
      system offers physicians a tool for systematic evaluation prior to prescribing
      opioids The system generates an opioid agreement between the patient and
      physician, and provides medicolegal documentation of the patient's condition.
      CONCLUSIONS: PODS should improve patient care, refine pain control, and reduce
      the incidence of opioid abuse. Research to determine how PODS affects clinical
      care is underway. Specially, the effectiveness and efficiency of providing care
      utilizing PODS will be evaluated in future studies.

PMID- 19594847
TI  - Serial therapeutic sacroiliac joint injections: a practice audit.
AB  - OBJECTIVE: To determine the long-term response to serial sacroiliac joint (SIJ)
      corticosteroid injections. Design. Retrospective practice audit. SETTING AND
      PATIENTS: Tertiary care spine center. Review of charts of all patients in a
      single practice who underwent diagnostic and therapeutic fluoroscopically guided
      SIJ injections with combined local anesthetic, long-acting corticosteroid, and
      contrast. MEASURES: Response was evaluated at 1 hour and again at follow-up
      clinic visits. Response to injection was graded as positive if there was > or
      =50% relief of the targeted pain during the local anesthetic phase and at least 2
      weeks of > or =50% relief afterward. If pain recurred, patients had to have been
      sufficiently satisfied with the relief to request repeat injection. RESULTS:
      There were 164 patients; 5 had incomplete records, 4 had <2 year follow-up. Of
      the 155 patients, 120 (77%) were positive responders; 45 were men and 75 were
      women; and the mean age was 48 (27-91) years. Sixty-nine had prior lumbar
      surgery. Mean duration of follow-up was 44 months (26-101). Two were lost to
      follow-up. The 118 positive responders received a mean of 2.7 injections per
      patient. Forty patients required 1 injection only, 29 required two, 22 required
      three, and 27 required four or more. The mean duration of response for those
      receiving >1 injection was 9.3 months per injection (1-58). There were no adverse
      events. CONCLUSIONS: SIJ corticosteroid injections appear to be an effective
      palliative treatment for selected patients with SIJ pain. Most patients whose
      pain is responsive to SIJ steroid injections improved sufficiently and remained
      well after 1 to 3 injections, but some required frequent injections on a long
      term basis.

PMID- 19594848
TI  - "I can't be what I want to be": children's narratives of chronic pain experiences
      and treatment outcomes.
AB  - BACKGROUND: Chronic or recurrent nonmalignant pain is a significant problem for
      many children and adolescents and often limits the child's participation in
      normal physical, academic, and social activities. OBJECTIVE: To better understand
      the impact of chronic or recurrent pain on children within the context of their
      own lives and experiences, using qualitative analysis, and to suggest the
      applications of the narrative method to clinical practice. DESIGN: Grounded
      theory and narrative analysis of in-depth semi-structured interviews conducted at
      baseline and 6-12 months following clinic intake. SETTING: Subject homes.
      PATIENTS: Fifty-three children ages 10-17 presenting with recurrent pain to a
      university-based pain clinic. This sample did not differ significantly from the
      overall clinic population during the study period. RESULTS: Five common themes
      were identified; these suggested that isolation, changed self-perception,
      activity limitations, concerns about barriers to future goals, and lack of
      medical validation were important to the children's perceived impact of pain on
      their lives. Five narratives were identified, each of which provided a coherent,
      integrated description of the factors and perspectives presented by a specific
      subset of children at baseline. These narratives were then compared against the
      children's reports of improvement in pain and functioning at 6-12 months; from
      this comparison, a sixth narrative of therapeutic change emerged for some of the
      children. CONCLUSIONS: The authors suggest that physicians and parents who take
      the initiative to elicit the child's narrative can help the child to rewrite the
      story to promote therapeutic change, a better outcome, and higher satisfaction.

PMID- 19594849
TI  - Age-related patterns in adaptation to cancer pain: a mixed-method study.
AB  - OBJECTIVE: Although older people make up the majority of cancer patients, little
      is known about aging and cancer pain. The objective of this study was to explore
      age-related patterns in adaptation to chronic cancer-related pain in younger and
      older patients. DESIGN: A mixed-method study combining quantitative measures with
      individual semi-structured interviews. Quantitative measures included the Brief
      Pain Inventory, Pain Management Index, Charlson Comorbidity Index, and Karnofsky
      Performance Status. SETTING: Two outpatient clinics (Palliative Care and Cancer
      Pain service) in an academic cancer hospital. PARTICIPANTS: Fifteen younger
      (average age: 48.9 +/- 4.9 years old) and 17 older (average age: 72.4 +/- 9.2
      years old) people with cancer-related pain. RESULTS: Two age-related adaptation
      outcomes emerged from the interviews: "Waiting to live" and "Living despite
      pain." Younger patients were more likely than older patients to be "Waiting to
      live." They felt that complete pain relief was necessary before their lives could
      move forward and reported feeling out of control, angry, and unable to accept
      their pain. Marital strain was common. "Living despite pain" was more frequent
      among older than younger patients. These patients accepted pain as an inevitable
      part of cancer, pursued life goals, and modified activities to maximize
      engagement. Marital growth was common. CONCLUSION: Older and younger cancer
      patients described different adaptations to cancer pain despite reporting
      comparable pain intensity and interference. Older patients adapted by employing
      accommodative strategies. Younger patients were less likely to use these
      strategies and struggled with accepting the losses associated with cancer pain.
      These findings may guide future research into age-related patterns in cancer pain
      and the development of psychosocial interventions tailored to patients' life
      stage challenges.

PMID- 19594850
TI  - Overriding the Jehovah's Witness patient's refusal of blood: a reply to Cahana,
      Weibel, and Hurst.
AB  - This article is a response to a survey on moral reasoning among Swiss health
      professionals that appeared in a recent issue of this journal. The authors of
      that survey inquired whether or not their respondents would give a blood
      transfusion to a Jehovah's Witness patient who clearly refused it. A substantial
      number of the respondents answered that they would override the patient's refusal
      and give the transfusion. The present article examines the two ethical rationales
      that were offered to explain the overriding respondents' answers and argues that
      neither one is ethically acceptable. It concludes with an account of the
      phenomenon of "motivated reasoning" that, so it is argued, better explains why
      the overriders would refuse to honor the Jehovah's Witness patient's transfusion
      refusal.

PMID- 19594852
TI  - A case series of pulsed radiofrequency treatment of myofascial trigger points and
      scar neuromas.
AB  - INTRODUCTION: Pulsed radiofrequency (PRF) current applied to nerve tissue to
      treat intractable pain has recently been proposed as a less neurodestructive
      alternative to continuous radiofrequency lesioning. Clinical reports using PRF
      have shown promise in the treatment of a variety of focal, neuropathic
      conditions. To date, scant data exist on the use of PRF to treat myofascial and
      neuromatous pain. METHODS: All cases in which PRF was used to treat myofascial
      (trigger point) and neuromatous pain within our practice were evaluated
      retrospectively for technique, efficacy, and complications. Trigger points were
      defined as localized, extremely tender areas in skeletal muscle that contained
      palpable, taut bands of muscle. RESULTS: Nine patients were treated over an 18
      month period. All patients had longstanding myofascial or neuromatous pain that
      was refractory to previous medical management, physical therapy, and trigger
      point injections. Eight out of nine patients experienced 75-100% reduction in
      their pain following PRF treatment at initial evaluation 4 weeks following
      treatment. Six out of nine (67%) patients experienced 6 months to greater than 1
      year of pain relief. One patient experienced no better relief in terms of degree
      of pain reduction or duration of benefit when compared with previous trigger
      point injections. No complications were noted. DISCUSSION: Our review suggests
      that PRF could be a minimally invasive, less neurodestructive treatment modality
      for these painful conditions and that further systematic evaluation of this
      treatment approach is warranted.

PMID- 19594851
TI  - Intranasal ketorolac for postoperative pain: a phase 3, double-blind, randomized
      study.
AB  - OBJECTIVE: Analgesic efficacy and tolerability of intranasal (IN) ketorolac was
      evaluated in postoperative patients in a randomized, double-blind, placebo
      controlled study. METHODS: Patients received IN ketorolac (31.5 mg) [DOSAGE ERROR
      CORRECTED] or placebo three times daily for up to 5 days, with access to morphine
      by patient controlled analgesia (PCA). Patients in a single-dose phase were
      removed from PCA 3 hours prior to the first study dose the day after surgery, and
      received a single IN ketorolac or placebo dose when visual analog scale scores
      were > or =40. RESULTS: Three hundred patients (N = 199 ketorolac, N = 101
      placebo) were enrolled following primarily hysterectomies (135/300, 45%) and hip
      replacements (100/300, 33%); 189 (N = 115 ketorolac, N = 74 placebo) entered the
      single-dose phase. Mean age was 52 years (range 19-81) and 69% of patients were
      women. The primary efficacy endpoint, the single-dose summed pain intensity
      difference score at 6 hours, was significantly higher in the ketorolac group
      compared with placebo (83.3 vs 37.2, P < 0.007), indicating greater pain
      reduction with ketorolac. Morphine use was reduced by 34% in the ketorolac group
      compared with the placebo group. The incidence of adverse events ( approximately
      98%) was similar in the two groups. The most common adverse events in both groups
      were nausea and vomiting. There was a trend in the ketorolac group for a lower
      incidence of opioid-related side effects such as constipation and pruritus. Nasal
      irritation occurred more frequently with ketorolac vs placebo (24% vs 2%).
      CONCLUSION: IN ketorolac was well tolerated and effective in treating moderate-to
      severe postoperative pain in inpatients; the convenience of IN dosing suggests
      that its usefulness in the ambulatory care setting should be evaluated.

PMID- 19594853
TI  - Allergic rhinitis in school-aged children with asthma - still under-diagnosed and
      under-treated? A retrospective study in a children's hospital.
AB  - Allergic rhinitis (AR) and asthma can be considered as manifestations of the same
      disease entity. The treatment of AR may improve also asthma symptoms. The aim of
      the study was to evaluate, how often AR is diagnosed and treated in patients with
      asthma. A retrospective chart review in the allergy and asthma unit of a
      secondary paediatric hospital. From 903 eligible 7- to 15-year-old children with
      doctor-diagnosed asthma, 372 were randomly included in the study. In all, 229
      patients (61.6%, 95% CI: 56.5-66.4%) had symptoms presumptive for AR. The
      diagnosis of AR was recorded in the patient records only for 87 patients (23.4%,
      95% CI: 19.4-28.0). There was evidence that children with AR or nasal symptoms
      had more severe asthma; 35% of the patients with AR, 23% with nasal symptoms
      without AR diagnosis and 12% without nasal symptoms required inhaled steroids and
      long-acting beta-agonists for asthma (p = 0.035). AR was both under-diagnosed and
      under-treated in school-aged children with doctor-diagnosed asthma.

PMID- 19594855
TI  - Title: Health-related and diabetes-related quality of life (QOL) in Japanese
      children and adolescents with type 1 and type 2 diabetes.
AB  - Background: To assess 1) the HR-QOL of primary, junior and high school children
      with type 1 and type 2 diabetes and to compare them with healthy school children
      and 2) To compare the DR-QOL and parents' QOL between type 1 and type 2 diabetes
      in Japan. Methods: Overall, 471 patients aged 9-18 years (368 with type 1 and 103
      with type 2 diabetes) and their parents were involved. QOL was assessed by self
      administered questionnaire. Results: The total score of HR-QOL for primary and
      junior school children with type 1 diabetes was significantly higher than that of
      those with type 2 diabetes and healthy controls. However, there were no
      significant differences in high school children. Some subscale of HR-QOL were
      significantly lower for children with type 2 diabetes than for children with type
      1 diabetes or healthy controls. The DR-QOL of children with type 1 and type 2
      diabetes did not significantly differ. The Family Burden and Family Involvement
      were significantly greater in parents of children with type 1 diabetes. There
      were significantly positive correlations between HR-QOL and DR-QOL in both
      groups. In type 1 diabetes only, there were significant negative correlations
      between HbA1c and some subscales of the HR-QOL and PDQOL, and weak positive
      correlation between HbA1c and Family Burden. Conclusions: The HR-QOL of school
      children with type 1 diabetes was higher than that of those with type 2 diabetes
      and healthy school children. The QOL of school children with type 1 diabetes was
      not impaired.

PMID- 19594854
TI  - The prevalence of food hypersensitivity in young adults.
AB  - rising prevalence of food hypersensitivity (FHS) and severe allergic reactions to
      foods have been reported in the last decade. However, little is known on the
      prevalence in young adults. This study estimated the prevalence of FHS to the
      most common allergenic foods in an unselected population of young adults. We
      investigated a cohort of 1272 young adults 22 years of age by questionnaire, skin
      prick test (SPT) and histamin release (HR) followed by oral challenge to the most
      common allergenic foods. FHS was divided into primary and secondary FHS. Primary
      FHS was defined as being independent of pollen sensitization, whereas secondary
      FHS was defined as reactions to pollen related fruits and vegetables in pollen
      allergic patients. The questionnaire was returned by 77.1%. Primary FHS was
      reported by 19.6% and secondary FHS by 16.7% of the participants. Confirmed
      primary FHS by oral challenge was 1.7% [1.1% - 2.95%]. In primary FHS, the most
      common allergenic food was peanut (0.6%) followed by additives (0.5%), shrimp
      (0.2%), codfish (0.1%), cow's milk (0.1%), octopus (0.1%) and soy (0.1%). In
      secondary FHS, kiwi allergy was reported by 7.8% of the participants followed by
      hazelnut (6.6%), pineapple (4.4%), apple (4.3%), orange (4.2%), tomato (3.8%),
      peach (3.0%) and brazil nut (2.7%). This study found a 1.7% [1.1% - 2.95%]
      prevalence of primary FHS confirmed by oral challenge to the most common
      allergenic foods in an unselected population of young adults.

PMID- 19594858
TI  - Language that puts you in touch with your bodily feelings: the multimodal
      responsiveness of affective expressions.
AB  - Observing and producing a smile activate the very same facial muscles. In
      Experiment 1, we predicted and found that verbal stimuli (action verbs) that
      refer to emotional expressions elicit the same facial muscle activity (facial
      electromyography) as visual stimuli do. These results are evidence that language
      referring to facial muscular activity is not amodal, as traditionally assumed,
      but is instead bodily grounded. These findings were extended in Experiment 2, in
      which subliminally presented verbal stimuli were shown to drive muscle activation
      and to shape judgments, but not when muscle activation was blocked. These
      experiments provide an important bridge between research on the neurobiological
      basis of language and related behavioral research. The implications of these
      findings for theories of language and other domains of cognitive psychology
      (e.g., priming) are discussed.

PMID- 19594857
TI  - Neural correlates of reward processing in adolescents with a history of inhibited
      temperament.
AB  - Functional imaging data were acquired during performance of a reward-contingency
      task in a unique cohort of adolescents (ages 14-18 years) who were characterized
      since infancy on measures of temperamental behavioral inhibition. Neural
      activation was examined in striatal structures (nucleus accumbens, putamen,
      caudate) with a known role in facilitating response to salient reward-related
      cues. Adolescents with a history of behavioral inhibition, relative to
      noninhibited adolescents, showed increased activation in the nucleus accumbens
      when they believed their selection of an action would affect reward outcome.
      Neural responses did not differ between the two groups when participants made a
      prespecified response that they knew would result in reward or when they produced
      random motor responses that they knew would not be rewarded. These results link
      inhibited temperament and perturbed neural responses to reward-contingency cues.

PMID- 19594860
TI  - Genes for psychosis and creativity: a promoter polymorphism of the neuregulin 1
      gene is related to creativity in people with high intellectual achievement.
AB  - Why are genetic polymorphisms related to severe mental disorders retained in the
      gene pool of a population? A possible answer is that these genetic variations may
      have a positive impact on psychological functions. Here, I show that a
      biologically relevant polymorphism of the promoter region of the neuregulin 1
      gene (SNP8NRG243177/rs6994992) is associated with creativity in people with high
      intellectual and academic performance. Intriguingly, the highest creative
      achievements and creative-thinking scores were found in people who carried the
      T/T genotype, which was previously shown to be related to psychosis risk and
      altered prefrontal activation.

PMID- 19594859
TI  - Choking on the money: reward-based performance decrements are associated with
      midbrain activity.
AB  - A pernicious paradox in human motivation is the occasional reduced performance
      associated with tasks and situations that involve larger-than-average rewards.
      Three broad explanations that might account for such performance decrements are
      attentional competition (distraction theories), inhibition by conscious processes
      (explicit-monitoring theories), and excessive drive and arousal (overmotivation
      theories). Here, we report incentive-dependent performance decrements in humans
      in a reward-pursuit task; subjects were less successful in capturing a more
      valuable reward in a computerized maze. Concurrent functional magnetic resonance
      imaging revealed that increased activity in ventral midbrain, a brain area
      associated with incentive motivation and basic reward responding, correlated with
      both reduced number of captures and increased number of near-misses associated
      with imminent high rewards. These data cast light on the neurobiological basis of
      choking under pressure and are consistent with overmotivation accounts.

PMID- 19594861
TI  - Distant memories: a prospective study of vantage point of trauma memories.
AB  - Adopting an observer perspective to recall trauma memories may function as a form
      of avoidance that maintains posttraumatic stress disorder (PTSD). We conducted a
      prospective study to analyze the relationship between memory vantage point and
      PTSD symptoms. Participants (N= 947) identified the vantage point of their trauma
      memory and reported PTSD symptoms within 4 weeks of the trauma; 730 participants
      repeated this process 12 months later. Initially recalling the trauma from an
      observer vantage point was related to more severe PTSD symptoms at that time and
      12 months later. Shifting from a field to an observer perspective a year after
      trauma was associated with greater PTSD severity at 12 months. These results
      suggest that remembering trauma from an observer vantage point is related to both
      immediate and ongoing PTSD symptoms.

PMID- 19594862
TI  - A systematic review of the importance of milk TGF-beta on immunological outcomes
      in the infant and young child.
AB  - Cytokines in milk like transforming growth factor-beta (TGF-beta) have been shown
      to induce oral tolerance in experimental animal studies. However, human studies
      are less consistent with these findings. The primary objective of this review was
      to conduct a systematic review of published studies on the association between
      TGF-beta identified in human milk and immunological outcomes in infancy and early
      childhood. Human prospective clinical studies were identified through MEDLINE,
      CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included: well
      described populations of mothers and infants, time of milk sampling,
      immunological outcome measures and analytical methods of TGF-beta determination.
      We considered a wide range of immunological outcomes in infancy and early
      childhood, such as wheeze, atopy, eczema and the immunoglobulin switch. Twelve
      human studies were included in the review and 67% showed a positive association
      with TGF-beta1 or TGF-beta2 demonstrating protection against allergy-related
      outcomes in infancy and early childhood. High variability in concentrations of
      TGF-beta was noted between and within studies, some of it explained by maternal
      history of atopy or by consumption of probiotics. Human milk TGF-beta appears to
      be essential in developing and maintaining appropriate immune responses in
      infants and may provide protection against adverse immunological outcomes,
      corroborating findings from experimental animal studies. Further large clinical
      studies in diverse human populations are indicated to confirm these results.

PMID- 19594863
TI  - Contact to cat or dog, allergies and parental education.
AB  - Whether or not associations between animal contact and allergy/atopy are
      homogeneous across social strata has not yet been investigated. The aim of this
      study was to estimate the association between animal contact (cat, dog) and
      allergy/atopy in 6-yr-old school beginners, stratified by parental educational
      level. A total of 30794, 6-yr old children participated in cross-sectional
      studies between 1991 and 2000 in Germany. Allergic sensitization to common
      aeroallergens and symptoms and diagnoses of atopic diseases (asthma, eczema, hay
      fever) were the dependent variables. Contact with dog/cat were the independent
      variables. Logistic regression was used to adjust for confounding. Analyses were
      stratified for parental education. Prevalences of hay fever, eczema, specific
      sensitization to pollen and house dust mite increased, while the prevalence of
      contact to cat and dog decreased with parental educational level. Globally
      significant positive associations between cat contact and sensitization to cat
      (interaction significant) and between dog contact and wheezing remained
      significant in the highest and medium/highest educational strata respectively. A
      globally significant inverse association between cat contact and hay fever
      remained significant in the highest educational stratum only. The inverse
      association of contact to dog with eczema was globally significant, but not in
      the strata. When estimating the associations between animal contact and
      allergy/atopy in children, effect modification by social status should be
      considered. Cat contact seems to increase the odds of sensitization to cat only
      in children whose parents have a high level of education.

PMID- 19594865
TI  - Cutaneous infection by Alternaria infectoria in a renal transplant patient.
AB  - Skin lesions are common in renal transplant recipients (RTR) and the clinical
      distinction of malignancy versus infection may be difficult in this patient
      population, with the need for further histological and biological investigations.
      We report here on a 73-year-old male RTR who presented with Alternaria infectoria
      phaeohyphomycosis of 1 year's duration. Mycological cultures were negative, and
      the diagnosis was performed by real-time polymerase chain reaction assay and
      direct sequencing. The extension of the lesion under itraconazole treatment
      required its surgical excision. Alternaria are ubiquitous plant-inhabiting
      saprobes, which are increasingly associated with opportunistic phaeohyphomycosis
      in immunocompromised individuals.

PMID- 19594864
TI  - A probiotic dairy product containing L. gasseri CECT5714 and L. coryniformis
      CECT5711 induces immunological changes in children suffering from allergy.
AB  - The increase in the prevalence of allergic diseases in children has been
      attributed to an unbalanced immune response probably due to environmental
      factors. The immunoregulatory properties of probiotic bacteria could balance the
      disequilibrium in the immune response causing the allergic response. The aim of
      this study was to evaluate the immunological effects of the consumption of a
      dairy product containing two probiotic strains in children suffering from
      allergy. A double-blinded, randomized, control comparative study was performed
      with 44 allergic children. Children were randomly distributed in two groups, a
      control Yogurt and a Probiotic group. Both groups daily consumed 200 ml of a
      dairy fermented product for 3 months. The Yogurt group consumed a conventional
      yogurt, whereas the Probiotic group consumed a similar dairy product where
      Lactobacillus bulgaricus was substituted by a mixture of Lactobacillus gasseri
      CECT5714 and Lactobacillus coryniformis CECT5711 (at least 10(6) cfu/g each
      strain). Intestinal and immunological parameters were measured in fecal and blood
      samples. The consumption of the probiotic product induced a significant decrease
      in the level of IgE in plasma (p = 0.03) and an increase in CD4(+)/CD25(+) T
      regulatory cells (p = 0.01). The decrease in IgE was accompanied by a significant
      increase in mucosal IgA (p = 0.01). However, changes in other effector cells
      potentially involved in allergic reactions such as eosinophiles, basophiles or
      other IgE+ cells were not detected. The consumption of the probiotic product also
      induced significant changes in innate response as a significant increase in
      natural killer cells was detected (p = 0.03). The daily consumption of a
      probiotic product containing L. gasseri CECT5714 and L. coryniformis CECT5711 for
      3 months induces, in allergic children, beneficial effects on immune parameters
      involved in the allergic response such as a reduction of IgE in plasma and an
      increase in regulatory T cells. The probiotic product also enhanced innate and
      specific immune parameters that may improve the general health status of
      children.

PMID- 19594866
TI  - Pancreas allograft thrombosis following intravenous immunoglobulin administration
      to treat parvovirus B19 infection.
AB  - Pancreas graft thrombosis is one of the commonest non-immunological causes for
      early graft loss after transplantation. This case report describes a patient who
      developed graft thrombosis after intravenous immunoglobulin administration to
      treat acute parvovirus B19 infection. The potential role of hypercoagulability in
      graft thrombosis and the implications for immunoglobulin therapy in transplant
      patients with hypercoagulable states is discussed.

PMID- 19594867
TI  - High-throughput next-generation sequencing technologies foster new cutting-edge
      computing techniques in bioinformatics.
AB  - The advent of high-throughput next generation sequencing technologies have
      fostered enormous potential applications of supercomputing techniques in genome
      sequencing, epi-genetics, metagenomics, personalized medicine, discovery of non
      coding RNAs and protein-binding sites. To this end, the 2008 International
      Conference on Bioinformatics and Computational Biology (Biocomp) - 2008 World
      Congress on Computer Science, Computer Engineering and Applied Computing
      (Worldcomp) was designed to promote synergistic inter/multidisciplinary research
      and education in response to the current research trends and advances. The
      conference attracted more than two thousand scientists, medical doctors,
      engineers, professors and students gathered at Las Vegas, Nevada, USA during July
      14-17 and received great success. Supported by International Society of
      Intelligent Biological Medicine (ISIBM), International Journal of Computational
      Biology and Drug Design (IJCBDD), International Journal of Functional Informatics
      and Personalized Medicine (IJFIPM) and the leading research laboratories from
      Harvard, M.I.T., Purdue, UIUC, UCLA, Georgia Tech, UT Austin, U. of Minnesota, U.
      of Iowa etc, the conference received thousands of research papers. Each submitted
      paper was reviewed by at least three reviewers and accepted papers were required
      to satisfy reviewers' comments. Finally, the review board and the committee
      decided to select only 19 high-quality research papers for inclusion in this
      supplement to BMC Genomics based on the peer reviews only. The conference
      committee was very grateful for the Plenary Keynote Lectures given by: Dr. Brian
      D. Athey (University of Michigan Medical School), Dr. Vladimir N. Uversky
      (Indiana University School of Medicine), Dr. David A. Patterson (Member of United
      States National Academy of Sciences and National Academy of Engineering,
      University of California at Berkeley) and Anousheh Ansari (Prodea Systems, Space
      Ambassador). The theme of the conference to promote synergistic research and
      education has been achieved successfully.

PMID- 19594868
TI  - Prediction of DNA-binding residues from protein sequence information using random
      forests.
AB  - BACKGROUND: Protein-DNA interactions are involved in many biological processes
      essential for cellular function. To understand the molecular mechanism of protein
      DNA recognition, it is necessary to identify the DNA-binding residues in DNA
      binding proteins. However, structural data are available for only a few hundreds
      of protein-DNA complexes. With the rapid accumulation of sequence data, it
      becomes an important but challenging task to accurately predict DNA-binding
      residues directly from amino acid sequence data. RESULTS: A new machine learning
      approach has been developed in this study for predicting DNA-binding residues
      from amino acid sequence data. The approach used both the labelled data instances
      collected from the available structures of protein-DNA complexes and the abundant
      unlabeled data found in protein sequence databases. The evolutionary information
      contained in the unlabeled sequence data was represented as position-specific
      scoring matrices (PSSMs) and several new descriptors. The sequence-derived
      features were then used to train random forests (RFs), which could handle a large
      number of input variables and avoid model overfitting. The use of evolutionary
      information was found to significantly improve classifier performance. The RF
      classifier was further evaluated using a separate test dataset, and the predicted
      DNA-binding residues were examined in the context of three-dimensional
      structures. CONCLUSION: The results suggest that the RF-based approach gives rise
      to more accurate prediction of DNA-binding residues than previous studies. A new
      web server called BindN-RF http://bioinfo.ggc.org/bindn-rf/ has thus been
      developed to make the RF classifier accessible to the biological research
      community.

PMID- 19594869
TI  - RBT-GA: a novel metaheuristic for solving the Multiple Sequence Alignment
      problem.
AB  - BACKGROUND: Multiple Sequence Alignment (MSA) has always been an active area of
      research in Bioinformatics. MSA is mainly focused on discovering biologically
      meaningful relationships among different sequences or proteins in order to
      investigate the underlying main characteristics/functions. This information is
      also used to generate phylogenetic trees. RESULTS: This paper presents a novel
      approach, namely RBT-GA, to solve the MSA problem using a hybrid solution
      methodology combining the Rubber Band Technique (RBT) and the Genetic Algorithm
      (GA) metaheuristic. RBT is inspired by the behavior of an elastic Rubber Band
      (RB) on a plate with several poles, which is analogues to locations in the input
      sequences that could potentially be biologically related. A GA attempts to mimic
      the evolutionary processes of life in order to locate optimal solutions in an
      often very complex landscape. RBT-GA is a population based optimization algorithm
      designed to find the optimal alignment for a set of input protein sequences. In
      this novel technique, each alignment answer is modeled as a chromosome consisting
      of several poles in the RBT framework. These poles resemble locations in the
      input sequences that are most likely to be correlated and/or biologically
      related. A GA-based optimization process improves these chromosomes gradually
      yielding a set of mostly optimal answers for the MSA problem. CONCLUSION: RBT-GA
      is tested with one of the well-known benchmarks suites (BALiBASE 2.0) in this
      area. The obtained results show that the superiority of the proposed technique
      even in the case of formidable sequences.

PMID- 19594870
TI  - Genomic and systems evolution in Vibrionaceae species.
AB  - BACKGROUND: The steadily increasing number of prokaryotic genomes has accelerated
      the study of genome evolution; in particular, the availability of sets of genomes
      from closely related bacteria has facilitated the exploration of the mechanisms
      underlying genome plasticity. The family Vibrionaceae is found in the
      Gammaproteobacteria and is abundant in aquatic environments. Taxa from the family
      Vibrionaceae are diversified in their life styles; some species are free living,
      others are symbiotic, and others are human pathogens. This diversity makes this
      family a useful set of model organisms for studying bacterial evolution. This
      evolution is driven by several forces, among them gene duplication and lateral
      gene transfer, which are believed to provide raw material for functional
      redundancy and novelty. The resultant gene copy increase in one genome is then
      detected as lineage-specific expansion (LSE). RESULTS: Here we present the
      results of a detailed comparison of the genomes of eleven Vibrionaceae strains
      that have distinct life styles and distinct phenotypes. The core genome shared by
      all eleven strains is composed of 1,882 genes, which make up about 31%-50% of the
      genome repertoire. We further investigated the distribution and features of genes
      that have been specifically expanded in one unique lineage of the eleven strains.
      Abundant duplicate genes have been identified in the eleven Vibrionaceae strains,
      with 1-11% of the whole genomes composed lineage specific radiations. These LSEs
      occurred in two distinct patterns: the first type yields one or more copies of a
      single gene; we call this a single gene expansion. The second pattern has a high
      evolutionary impact, as the expansion involves two or more gene copies in a
      block, with the duplicated block located next to the original block (a contiguous
      block expansion) or at some distance from the original block (a discontiguous
      block expansion). We showed that LSEs involve genes that are tied to defense and
      pathogenesis mechanisms as well as in the fundamental life cycle of Vibrionaceae
      species. CONCLUSION: Our results provide evidence of genome plasticity and rapid
      evolution within the family Vibrionaceae. The comparisons point to sources of
      genomic variation and candidates for lineage-specific adaptations of each
      Vibrionaceae pathogen or nonpathogen strain. Such lineage specific expansions
      could reveal components in bacterial systems that, by their enhanced genetic
      variability, can be tied to responses to environmental challenges, interesting
      phenotypes, or adaptive pathogenic responses to host challenges.

PMID- 19594871
TI  - Protein disorder in the human diseasome: unfoldomics of human genetic diseases.
AB  - BACKGROUND: Intrinsically disordered proteins lack stable structure under
      physiological conditions, yet carry out many crucial biological functions,
      especially functions associated with regulation, recognition, signaling and
      control. Recently, human genetic diseases and related genes were organized into a
      bipartite graph (Goh KI, Cusick ME, Valle D, Childs B, Vidal M, et al. (2007) The
      human disease network. Proc Natl Acad Sci U S A 104: 8685-8690). This diseasome
      network revealed several significant features such as the common genetic origin
      of many diseases. METHODS AND FINDINGS: We analyzed the abundance of intrinsic
      disorder in these diseasome network proteins by means of several prediction
      algorithms, and we analyzed the functional repertoires of these proteins based on
      prior studies relating disorder to function. Our analyses revealed that (i)
      Intrinsic disorder is common in proteins associated with many human genetic
      diseases; (ii) Different disease classes vary in the IDP contents of their
      associated proteins; (iii) Molecular recognition features, which are relatively
      short loosely structured protein regions within mostly disordered sequences and
      which gain structure upon binding to partners, are common in the diseasome, and
      their abundance correlates with the intrinsic disorder level; (iv) Some disease
      classes have a significant fraction of genes affected by alternative splicing,
      and the alternatively spliced regions in the corresponding proteins are predicted
      to be highly disordered; and (v) Correlations were found among the various
      diseasome graph-related properties and intrinsic disorder. CONCLUSION: These
      observations provide the basis for the construction of the human-genetic-disease
      associated unfoldome.

PMID- 19594873
TI  - Differences in duplication age distributions between human GPCRs and their
      downstream genes from a network prospective.
AB  - BACKGROUND: How gene duplication has influenced the evolution of gene networks is
      one of the core problems in evolution. Current duplication-divergence theories
      generally suggested that genes on the periphery of the networks were
      preferentially retained after gene duplication. However, previous studies were
      mostly based on gene networks in invertebrate species, and they had the inherent
      shortcoming of not being able to provide information on how the duplication
      divergence process proceeded along the time axis during major speciation events.
      RESULTS: In this study, we constructed a model system consisting of human G
      protein-coupled receptors (GPCRs) and their downstream genes in the GPCR
      pathways. These two groups of genes offered a natural partition of genes in the
      peripheral and the backbone layers of the network. Analysis of the age
      distributions of the duplication events in human GPCRs and "downstream genes"
      gene families indicated that they both experienced an explosive expansion at the
      time of early vertebrate emergence. However, we found only GPCR families saw a
      continued expansion after early vertebrates, mostly prominently in several small
      subfamilies of GPCRs involved in immune responses and sensory responses.
      CONCLUSION: In general, in the human GPCR model system, we found that the
      position of a gene in the gene networks has significant influences on the
      likelihood of fixation of its duplicates. However, for a super gene family, the
      influence was not uniform among subfamilies. For super families, such as GPCRs,
      whose gene basis of expression diversity was well established at early
      vertebrates, continued expansions were mostly prominent in particular small
      subfamilies mainly involved in lineage-specific functions.

PMID- 19594872
TI  - PDA: an automatic and comprehensive analysis program for protein-DNA complex
      structures.
AB  - BACKGROUND: Knowledge of protein-DNA interactions at the structural-level can
      provide insights into the mechanisms of protein-DNA recognition and gene
      regulation. Although over 1400 protein-DNA complex structures have been deposited
      into Protein Data Bank (PDB), the structural details of protein-DNA interactions
      are generally not available. In addition, current approaches to comparison of
      protein-DNA complexes are mainly based on protein sequence similarity while the
      DNA sequences are not taken into account. With the number of experimentally
      determined protein-DNA complex structures increasing, there is a need for an
      automatic program to analyze the protein-DNA complex structures and to provide
      comprehensive structural information for the benefit of the whole research
      community. RESULTS: We developed an automatic and comprehensive protein-DNA
      complex structure analysis program, PDA (for protein-DNA complex structure
      analyzer). PDA takes PDB files as inputs and performs structural analysis that
      includes 1) whole protein-DNA complex structure restoration, especially the
      reconstruction of double-stranded DNA structures; 2) an efficient new approach
      for DNA base-pair detection; 3) systematic annotation of protein-DNA
      interactions; and 4) extraction of DNA subsequences involved in protein-DNA
      interactions and identification of protein-DNA binding units. Protein-DNA complex
      structures in current PDB were processed and analyzed with our PDA program and
      the analysis results were stored in a database. A dataset useful for studying
      protein-DNA interactions involved in gene regulation was generated using both
      protein and DNA sequences as well as the contact information of the complexes.
      WebPDA was developed to provide a web interface for using PDA and for data
      retrieval. CONCLUSION: PDA is a computational tool for structural annotations of
      protein-DNA complexes. It provides a useful resource for investigating protein
      DNA interactions. Data from the PDA analysis can also facilitate the
      classification of protein-DNA complexes and provide insights into rational design
      of benchmarks. The PDA program is freely available at
      http://bioinfozen.uncc.edu/webpda.

PMID- 19594874
TI  - Reverse engineering module networks by PSO-RNN hybrid modeling.
AB  - BACKGROUND: Inferring a gene regulatory network (GRN) from high throughput
      biological data is often an under-determined problem and is a challenging task
      due to the following reasons: (1) thousands of genes are involved in one living
      cell; (2) complex dynamic and nonlinear relationships exist among genes; (3) a
      substantial amount of noise is involved in the data, and (4) the typical small
      sample size is very small compared to the number of genes. We hypothesize we can
      enhance our understanding of gene interactions in important biological processes
      (differentiation, cell cycle, and development, etc) and improve the inference
      accuracy of a GRN by (1) incorporating prior biological knowledge into the
      inference scheme, (2) integrating multiple biological data sources, and (3)
      decomposing the inference problem into smaller network modules. RESULTS: This
      study presents a novel GRN inference method by integrating gene expression data
      and gene functional category information. The inference is based on module
      network model that consists of two parts: the module selection part and the
      network inference part. The former determines the optimal modules through fuzzy c
      mean (FCM) clustering and by incorporating gene functional category information,
      while the latter uses a hybrid of particle swarm optimization and recurrent
      neural network (PSO-RNN) methods to infer the underlying network between modules.
      Our method is tested on real data from two studies: the development of rat
      central nervous system (CNS) and the yeast cell cycle process. The results are
      evaluated by comparing them to previously published results and gene ontology
      annotation information. CONCLUSION: The reverse engineering of GRNs in time
      course gene expression data is a major obstacle in system biology due to the
      limited number of time points. Our experiments demonstrate that the proposed
      method can address this challenge by: (1) preprocessing gene expression data
      (e.g. normalization and missing value imputation) to reduce the data noise; (2)
      clustering genes based on gene expression data and gene functional category
      information to identify biologically meaningful modules, thereby reducing the
      dimensionality of the data; (3) modeling GRNs with the PSO-RNN method between the
      modules to capture their nonlinear and dynamic relationships. The method is shown
      to lead to biologically meaningful modules and networks among the modules.

PMID- 19594875
TI  - HAPPI: an online database of comprehensive human annotated and predicted protein
      interactions.
AB  - BACKGROUND: Human protein-protein interaction (PPIs) data are the foundation for
      understanding molecular signalling networks and the functional roles of
      biomolecules. Several human PPI databases have become available; however,
      comparisons of these datasets have suggested limited data coverage and poor data
      quality. Ongoing collection and integration of human PPIs from different sources,
      both experimentally and computationally, can enable disease-specific network
      biology modelling in translational bioinformatics studies. RESULTS: We developed
      a new web-based resource, the Human Annotated and Predicted Protein Interaction
      (HAPPI) database, located at http://bio.informatics.iupui.edu/HAPPI/. The HAPPI
      database was created by extracting and integrating publicly available protein
      interaction databases, including HPRD, BIND, MINT, STRING, and OPHID, using
      database integration techniques. We designed a unified entity-relationship data
      model to resolve semantic level differences of diverse concepts involved in PPI
      data integration. We applied a unified scoring model to give each PPI a measure
      of its reliability that can place each PPI at one of the five star rank levels
      from 1 to 5. We assessed the quality of PPIs contained in the new HAPPI database,
      using evolutionary conserved co-expression pairs called "MetaGene" pairs to
      measure the extent of MetaGene pair and PPI pair overlaps. While the overall
      quality of the HAPPI database across all star ranks is comparable to the overall
      qualities of HPRD or IntNetDB, the subset of the HAPPI database with star ranks
      between 3 and 5 has a much higher average quality than all other human PPI
      databases. As of summer 2008, the database contains 142,956 non-redundant, medium
      to high-confidence level human protein interaction pairs among 10,592 human
      proteins. The HAPPI database web application also provides ..." should be "The
      HAPPI database web application also provides hyperlinked information of genes,
      pathways, protein domains, protein structure displays, and sequence feature maps
      for interactive exploration of PPI data in the database. CONCLUSION: HAPPI is by
      far the most comprehensive public compilation of human protein interaction
      information. It enables its users to fully explore PPI data with quality measures
      and annotated information necessary for emerging network biology studies.

PMID- 19594876
TI  - Comparing 2-nt 3' overhangs against blunt-ended siRNAs: a systems biology based
      study.
AB  - In this study, we formulate a computational reaction model following a chemical
      kinetic theory approach to predict the binding rate constant for the siRNA-RISC
      complex formation reaction. The model allowed us to study the potency difference
      between 2-nt 3' overhangs against blunt-ended siRNA molecules in an RNA
      interference (RNAi) system. The rate constant predicted by this model was fed
      into a stochastic simulation of the RNAi system (using the Gillespie stochastic
      simulator) to study the overall potency effect. We observed that the
      stochasticity in the transcription/translation machinery has no observable
      effects in the RNAi pathway. Sustained gene silencing using siRNAs can be
      achieved only if there is a way to replenish the dsRNA molecules in the cell.
      Initial findings show about 1.5 times more blunt-ended molecules will be required
      to keep the mRNA at the same reduced level compared to the 2-nt overhang siRNAs.
      However, the mRNA levels jump back to saturation after a longer time when blunt
      ended siRNAs are used. We found that the siRNA-RISC complex formation reaction
      rate was 2 times slower when blunt-ended molecules were used pointing to the fact
      that the presence of the 2-nt overhangs has a greater effect on the reaction in
      which the bound RISC complex cleaves the mRNA.

PMID- 19594877
TI  - Word-based characterization of promoters involved in human DNA repair pathways.
AB  - BACKGROUND: DNA repair genes provide an important contribution towards the
      surveillance and repair of DNA damage. These genes produce a large network of
      interacting proteins whose mRNA expression is likely to be regulated by similar
      regulatory factors. Full characterization of promoters of DNA repair genes and
      the similarities among them will more fully elucidate the regulatory networks
      that activate or inhibit their expression. To address this goal, the authors
      introduce a technique to find regulatory genomic signatures, which represents a
      specific application of the genomic signature methodology to classify DNA
      sequences as putative functional elements within a single organism. RESULTS: The
      effectiveness of the regulatory genomic signatures is demonstrated via analysis
      of promoter sequences for genes in DNA repair pathways of humans. The promoters
      are divided into two classes, the bidirectional promoters and the unidirectional
      promoters, and distinct genomic signatures are calculated for each class. The
      genomic signatures include statistically overrepresented words, word clusters,
      and co-occurring words. The robustness of this method is confirmed by the ability
      to identify sequences that exist as motifs in TRANSFAC and JASPAR databases, and
      in overlap with verified binding sites in this set of promoter regions.
      CONCLUSION: The word-based signatures are shown to be effective by finding
      occurrences of known regulatory sites. Moreover, the signatures of the
      bidirectional and unidirectional promoters of human DNA repair pathways are
      clearly distinct, exhibiting virtually no overlap. In addition to providing an
      effective characterization method for related DNA sequences, the signatures
      elucidate putative regulatory aspects of DNA repair pathways, which are notably
      under-characterized.

PMID- 19594878
TI  - A Distribution-Free Convolution Model for background correction of
      oligonucleotide microarray data.
AB  - INTRODUCTION: Affymetrix GeneChip high-density oligonucleotide arrays are widely
      used in biological and medical research because of production reproducibility,
      which facilitates the comparison of results between experiment runs. In order to
      obtain high-level classification and cluster analysis that can be trusted, it is
      important to perform various pre-processing steps on the probe-level data to
      control for variability in sample processing and array hybridization. Many
      proposed preprocessing methods are parametric, in that they assume that the
      background noise generated by microarray data is a random sample from a
      statistical distribution, typically a normal distribution. The quality of the
      final results depends on the validity of such assumptions. RESULTS: We propose a
      Distribution Free Convolution Model (DFCM) to circumvent observed deficiencies in
      meeting and validating distribution assumptions of parametric methods. Knowledge
      of array structure and the biological function of the probes indicate that the
      intensities of mismatched (MM) probes that correspond to the smallest perfect
      match (PM) intensities can be used to estimate the background noise.
      Specifically, we obtain the smallest q2 percent of the MM intensities that are
      associated with the lowest q1 percent PM intensities, and use these intensities
      to estimate background. CONCLUSION: Using the Affymetrix Latin Square spike-in
      experiments, we show that the background noise generated by microarray
      experiments typically is not well modeled by a single overall normal
      distribution. We further show that the signal is not exponentially distributed,
      as is also commonly assumed. Therefore, DFCM has better sensitivity and
      specificity, as measured by ROC curves and area under the curve (AUC) than MAS
      5.0, RMA, RMA with no background correction (RMA-noBG), GCRMA, PLIER, and dChip
      (MBEI) for preprocessing of Affymetrix microarray data. These results hold for
      two spike-in data sets and one real data set that were analyzed. Comparisons with
      other methods on two spike-in data sets and one real data set show that our
      nonparametric methods are a superior alternative for background correction of
      Affymetrix data.

PMID- 19594879
TI  - Reconstruct gene regulatory network using slice pattern model.
AB  - BACKGROUND: Gene expression time series array data has become a useful resource
      for investigating gene functions and the interactions between genes. However, the
      gene expression arrays are always mixed with noise, and many nonlinear regulatory
      relationships have been omitted in many linear models. Because of those practical
      limitations, inference of gene regulatory model from expression data is still far
      from satisfactory. RESULTS: In this study, we present a model-based computational
      approach, Slice Pattern Model (SPM), to identify gene regulatory network from
      time series gene expression array data. In order to estimate performances of
      stability and reliability of our model, an artificial gene network is tested by
      the traditional linear model and SPM. SPM can handle the multiple transcriptional
      time lags and more accurately reconstruct the gene network. Using SPM, a 17 time
      series gene expression data in yeast cell cycle is retrieved to reconstruct the
      regulatory network. Under the reliability threshold, theta = 55%, 18
      relationships between genes are identified and transcriptional regulatory network
      is reconstructed. Results from previous studies demonstrate that most of gene
      relationships identified by SPM are correct. CONCLUSION: With the help of pattern
      recognition and similarity analysis, the effect of noise has been limited in SPM
      method. At the same time, genetic algorithm is introduced to optimize parameters
      of gene network model, which is performed based on a statistic method in our
      experiments. The results of experiments demonstrate that the gene regulatory
      model reconstructed using SPM is more stable and reliable than those models
      coming from traditional linear model.

PMID- 19594880
TI  - Comparison of feature selection and classification for MALDI-MS data.
AB  - INTRODUCTION: In the classification of Mass Spectrometry (MS) proteomics data,
      peak detection, feature selection, and learning classifiers are critical to
      classification accuracy. To better understand which methods are more accurate
      when classifying data, some publicly available peak detection algorithms for
      Matrix assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) data
      were recently compared; however, the issue of different feature selection methods
      and different classification models as they relate to classification performance
      has not been addressed. With the application of intelligent computing, much
      progress has been made in the development of feature selection methods and
      learning classifiers for the analysis of high-throughput biological data. The
      main objective of this paper is to compare the methods of feature selection and
      different learning classifiers when applied to MALDI-MS data and to provide a
      subsequent reference for the analysis of MS proteomics data. RESULTS: We compared
      a well-known method of feature selection, Support Vector Machine Recursive
      Feature Elimination (SVMRFE), and a recently developed method, Gradient based
      Leave-one-out Gene Selection (GLGS) that effectively performs microarray data
      analysis. We also compared several learning classifiers including K-Nearest
      Neighbor Classifier (KNNC), Naive Bayes Classifier (NBC), Nearest Mean Scaled
      Classifier (NMSC), uncorrelated normal based quadratic Bayes Classifier recorded
      as UDC, Support Vector Machines, and a distance metric learning for Large Margin
      Nearest Neighbor classifier (LMNN) based on Mahanalobis distance. To compare, we
      conducted a comprehensive experimental study using three types of MALDI-MS data.
      CONCLUSION: Regarding feature selection, SVMRFE outperformed GLGS in
      classification. As for the learning classifiers, when classification models
      derived from the best training were compared, SVMs performed the best with
      respect to the expected testing accuracy. However, the distance metric learning
      LMNN outperformed SVMs and other classifiers on evaluating the best testing. In
      such cases, the optimum classification model based on LMNN is worth investigating
      for future study.

PMID- 19594881
TI  - Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre
      mRNA alternative splicing.
AB  - BACKGROUND: Human genes undergo various patterns of pre-mRNA splicing across
      different tissues. Such variation is primarily regulated by trans-acting factors
      that bind on exonic and intronic cis-acting RNA elements (CAEs). Here we report a
      computational method to mechanistically identify cis-acting RNA elements that
      contribute to the tissue-specific alternative splicing pattern. This method is an
      extension of our previous model, SplicingModeler, which predicts the significant
      CAEs that contribute to the splicing differences between two tissues. In this
      study, we introduce tissue-specific functional levels estimation step, which
      allows evaluating regulatory functions of predicted CAEs that are involved in
      more than two tissues. RESULTS: Using a publicly available Affymetrix Genechip
      Human Exon Array dataset, our method identifies 652 cis-acting RNA elements
      (CAEs) across 11 human tissues. About one third of predicted CAEs can be mapped
      to the known RBP (RNA binding protein) binding sites or match with other
      predicted exonic splicing regulator databases. Interestingly, the vast majority
      of predicted CAEs are in intronic regulatory regions. A noticeable exception is
      that many exonic elements are found to regulate the alternative splicing between
      cerebellum and testes. Most identified elements are found to contribute to the
      alternative splicing between two tissues, while some are important in multiple
      tissues. This suggests that genome-wide alternative splicing patterns are
      regulated by a combination of tissue-specific cis-acting elements and "general
      elements" whose functional activities are important but differ across multiple
      tissues. CONCLUSION: In this study, we present a model-based computational
      approach to identify potential cis-acting RNA elements by considering the exon
      splicing variation as the combinatorial effects of multiple cis-acting
      regulators. This methodology provides a novel evaluation on the functional levels
      of cis-acting RNA elements by estimating their tissue-specific functions on
      various tissues.

PMID- 19594882
TI  - Comprehensive splicing graph analysis of alternative splicing patterns in
      chicken, compared to human and mouse.
AB  - BACKGROUND: Alternative transcript diversity manifests itself as a prime cause of
      complexity in higher eukaryotes. Recently, transcript diversity studies have
      suggested that 60-80% of human genes are alternatively spliced. We have used a
      splicing pattern approach for the bioinformatics analysis of Alternative Splicing
      (AS) in chicken, human and mouse. Exons involved in splicing are subdivided into
      distinct and variant exons, based on the prevalence of the exons across the
      transcripts. Four possible permutations of these two different groups of exons
      were categorised as class I (distinct-variant), class II (distinct-variant),
      class III (variant-distinct) and class IV (variant-variant). This classification
      quantifies the variation in transcript diversity in the three species. RESULTS:
      In all, 3901 chicken AS genes have been compared with 16,715 human and 16,491
      mouse AS genes, with 23% of chicken genes being alternatively spliced, compared
      to 68% in humans and 57% in mice. To minimize any gene structure bias in the
      input data, comparative genome analysis has been carried out on the orthologous
      subset of AS genes for the three species. Gene-level analysis suggested that
      chicken genes show fewer AS events compared to human and mouse. An event-level
      analysis showed that the percentage of AS events in chicken is similar to that of
      human, which implies that a smaller number of chicken genes show greater
      transcript diversity. Overall, chicken genes were found to have fewer transcripts
      per gene and shorter introns than human and mouse genes. CONCLUSION: In chicken,
      the majority of genes generate only two or three isoforms, compared to almost
      eight in human and six in mouse. We observed that intron definition is expressed
      strongly when compared to exon definition for chicken genome, based on 3% intron
      retention in chicken, compared to 2% in human and mouse. Splicing patterns with
      variant exons account for 33% of AS chicken orthologous genes compared to 24% in
      human and 27% in mouse, providing a novel measure to describe the species-wise
      complexity due to alternative transcript diversity.

PMID- 19594883
TI  - Annotating the human genome with Disease Ontology.
AB  - BACKGROUND: The human genome has been extensively annotated with Gene Ontology
      for biological functions, but minimally computationally annotated for diseases.
      RESULTS: We used the Unified Medical Language System (UMLS) MetaMap Transfer tool
      (MMTx) to discover gene-disease relationships from the GeneRIF database. We
      utilized a comprehensive subset of UMLS, which is disease-focused and structured
      as a directed acyclic graph (the Disease Ontology), to filter and interpret
      results from MMTx. The results were validated against the Homayouni gene
      collection using recall and precision measurements. We compared our results with
      the widely used Online Mendelian Inheritance in Man (OMIM) annotations.
      CONCLUSION: The validation data set suggests a 91% recall rate and 97% precision
      rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98%
      precision using OMIM. Our thesaurus-based approach allows for comparisons to be
      made between disease containing databases and allows for increased accuracy in
      disease identification through synonym matching. The much higher recall rate of
      our approach demonstrates that annotating human genome with Disease Ontology and
      GeneRIF for diseases dramatically increases the coverage of the disease
      annotation of human genome.

PMID- 19594885
TI  - An ensemble learning approach to reverse-engineering transcriptional regulatory
      networks from time-series gene expression data.
AB  - BACKGROUND: One of the most challenging tasks in the post-genomic era is to
      reconstruct the transcriptional regulatory networks. The goal is to reveal, for
      each gene that responds to a certain biological event, which transcription
      factors affect its expression, and how a set of transcription factors coordinate
      to accomplish temporal and spatial specific regulations. RESULTS: Here we propose
      a supervised machine learning approach to address these questions. We focus our
      study on the gene transcriptional regulation of the cell cycle in the budding
      yeast, thanks to the large amount of data available and relatively well
      understood biology, although the main ideas of our method can be applied to other
      data as well. Our method starts with building an ensemble of decision trees for
      each microarray data to capture the association between the expression levels of
      yeast genes and the binding of transcription factors to gene promoter regions, as
      determined by chromatin immunoprecipitation microarray (ChIP-chip) experiment.
      Cross-validation experiments show that the method is more accurate and reliable
      than the naive decision tree algorithm and several other ensemble learning
      methods. From the decision tree ensembles, we extract logical rules that explain
      how a set of transcription factors act in concert to regulate the expression of
      their targets. We further compute a profile for each rule to show its regulation
      strengths at different time points. We also propose a spline interpolation method
      to integrate the rule profiles learned from several time series expression data
      sets that measure the same biological process. We then combine these rule
      profiles to build a transcriptional regulatory network for the yeast cell cycle.
      Compared to the results in the literature, our method correctly identifies all
      major known yeast cell cycle transcription factors, and assigns them into
      appropriate cell cycle phases. Our method also identifies many interesting
      synergetic relationships among these transcription factors, most of which are
      well known, while many of the rest can also be supported by other evidences.
      CONCLUSION: The high accuracy of our method indicates that our method is valid
      and robust. As more gene expression and transcription factor binding data become
      available, we believe that our method is useful for reconstructing large-scale
      transcriptional regulatory networks in other species as well.

PMID- 19594884
TI  - Unfoldomics of human diseases: linking protein intrinsic disorder with diseases.
AB  - BACKGROUND: Intrinsically disordered proteins (IDPs) and intrinsically disordered
      regions (IDRs) lack stable tertiary and/or secondary structure yet fulfills key
      biological functions. The recent recognition of IDPs and IDRs is leading to an
      entire field aimed at their systematic structural characterization and at
      determination of their mechanisms of action. Bioinformatics studies showed that
      IDPs and IDRs are highly abundant in different proteomes and carry out mostly
      regulatory functions related to molecular recognition and signal transduction.
      These activities complement the functions of structured proteins. IDPs and IDRs
      were shown to participate in both one-to-many and many-to-one signaling.
      Alternative splicing and posttranslational modifications are frequently used to
      tune the IDP functionality. Several individual IDPs were shown to be associated
      with human diseases, such as cancer, cardiovascular disease, amyloidoses,
      diabetes, neurodegenerative diseases, and others. This raises questions regarding
      the involvement of IDPs and IDRs in various diseases. RESULTS: IDPs and IDRs were
      shown to be highly abundant in proteins associated with various human maladies.
      As the number of IDPs related to various diseases was found to be very large, the
      concepts of the disease-related unfoldome and unfoldomics were introduced. Novel
      bioinformatics tools were proposed to populate and characterize the disease
      associated unfoldome. Structural characterization of the members of the disease
      related unfoldome requires specialized experimental approaches. IDPs possess a
      number of unique structural and functional features that determine their broad
      involvement into the pathogenesis of various diseases. CONCLUSION: Proteins
      associated with various human diseases are enriched in intrinsic disorder. These
      disease-associated IDPs and IDRs are real, abundant, diversified, vital, and
      dynamic. These proteins and regions comprise the disease-related unfoldome, which
      covers a significant part of the human proteome. Profound association between
      intrinsic disorder and various human diseases is determined by a set of unique
      structural and functional characteristics of IDPs and IDRs. Unfoldomics of human
      diseases utilizes unrivaled bioinformatics and experimental techniques, paves the
      road for better understanding of human diseases, their pathogenesis and molecular
      mechanisms, and helps develop new strategies for the analysis of disease-related
      proteins.

PMID- 19594886
TI  - Energy profile and secondary structure impact shRNA efficacy.
AB  - BACKGROUND: RNA interference (RNAi) is a cellular mechanism in which a
      short/small double stranded RNA induces the degradation of its sequence specific
      target mRNA, leading to specific gene silencing. Since its discovery, RNAi has
      become a powerful biological technique for gene function studies and drug
      discovery. The very first requirement of applying RNAi is to design functional
      small interfering RNA (siRNA) that can uniquely induce the degradation of the
      targeted mRNA. It has been shown that many functional synthetic siRNAs share some
      common characteristics, such as GC content limitation and free energy preferences
      at both terminals, etc. RESULTS: Our three-phase algorithm was developed to
      design siRNA on a whole-genome scale based on those identified characteristics of
      functional siRNA. When this algorithm was applied to design short hairpin RNA
      (shRNA), the validated success rate of shRNAs was over 70%, which was almost
      double the rate reported for TRC library. This indicates that the designs of
      siRNA and shRNA may share the same concerns. Further analysis of the shRNA
      dataset of 444 designs reveals that the high free energy states of the two
      terminals have the largest positive impact on the shRNA efficacy. Enforcing these
      energy characteristics of both terminals can further improve the shRNA design
      success rate to 83.1%. We also found that functional shRNAs have less probability
      for their 3' terminals to be involved in mRNA secondary structure formation.
      CONCLUSION: Functional shRNAs prefer high free energy states at both terminals.
      High free energy states of the two terminals were found to be the largest
      positive impact factor on shRNA efficacy. In addition, the accessibility of the
      3' terminal is another key factor to shRNA efficacy.

PMID- 19594888
TI  - In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia
      euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures.
AB  - BACKGROUND: Shikonin derivatives have cytotoxic and antitumor effects. This study
      aims to investigate the antitumor effects of acetylshikonin isolated from a
      Chinese medicinal herb Arnebia euchroma (Royle) Johnst. METHODS: The 3-(4,5
      dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to
      determine the in vitro antitumor effects of acetylshikonin on human lung
      adenocarcinoma cell line A549, human hepatocellular carcinoma cell line Bel-7402,
      human breast adenocarcinoma cell line MCF-7 and mouse Lewis lung carcinoma (LLC)
      cell line. C57BL/6 mice with LLC model were used to study the in vivo antitumor
      effects of acetylshikonin. The expression of bax, bcl-2 and caspase-3 proteins in
      LLC tissue was determined with immunohistochemical staining. RESULTS: In A549,
      Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a
      dose-dependent manner. IC50 (means +/- SD) were 5.6 +/- 0.86 microg/ml, 6.82 +/-
      1.5 microg/ml, 3.04 +/- 0.44 microg/ml and 2.72 +/- 0.38 microg/ml respectively.
      Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition
      rate of acetylshikonin (2 mg/kg) was 42.85%. Immunohistochemical staining
      revealed that in the acetylshikonin groups the expression of bax and caspase-3
      increased, whereas the expression of bcl-2 decreased, suggesting that
      acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic
      bcl-2 family and caspase-3. CONCLUSION: Acetylshikonin isolated from Arnebia
      euchroma (Royle) Johnst cell suspension cultures exhibits specific in vivo and in
      vitro antitumor effects.

PMID- 19594889
TI  - Offense related characteristics and psychosexual development of juvenile sex
      offenders.
AB  - OBJECTIVE: This article reports on offense related characteristics and the
      psychosexual development in subgroups of juvenile sex offenders as measured by
      the Global Assessment Instrument for Juvenile Sex Offenders (GAIJSO). The
      predictive validity of these characteristics for persistent (sexual) offensive
      behavior in subgroups of juvenile sex offenders was investigated. METHODS: One
      hundred seventy four sex offenders (mean age 14.9 SD 1.4) referred by the police
      to the Dutch Child Protection Board were examined. Offense related
      characteristics were assessed by means of the GAIJSO and the BARO (a global
      assessment tool for juvenile delinquents), and criminal careers of the subjects
      were ascertained from official judicial records. RESULTS: Serious need for
      comprehensive diagnostics were found on the domains sexual offense and
      psychosexual development in juvenile sex offenders, especially in the group of
      child molesters. These youngsters displayed more internalizing and (psychosexual)
      developmental problems and their sexual offense was more alarming as compared to
      the other juvenile sex offender subgroups. Although one third of the juveniles
      had already committed one or more sex offenses prior to the index offense, at
      follow up (mean follow up period: 36 months SD 18 months) almost no sexual
      recidivism was found (0.6% of the entire sample). However, a substantial
      proportion of the entire sample of juvenile sex offenders showed non-sexual
      (55.6%) and violent recidivism (32.1%). Several predictors for a history of
      multiple sex offending and non-sexual recidivism were identified. CONCLUSION:
      This study revealed numerous problems in juvenile sex offenders. Assessment using
      the GAIJSO is helpful in order to identify indicators for extensive diagnostic
      assessment. In order to investigate the predictive validity for sexual
      reoffending a longer follow up period is necessary.

PMID- 19594891
TI  - Associations between statins and COPD: a systematic review.
AB  - BACKGROUND: Statins have anti-inflammatory and immunomodulating properties which
      could possibly influence inflammatory airways disease. We assessed evidence for
      disease modifying effects of statin treatment in patients with chronic
      obstructive pulmonary disease (COPD). METHODS: A systematic review was conducted
      of studies which reported effects of statin treatment in COPD. Data sources
      searched included MEDLINE, EMBASE and reference lists. RESULTS: Eight papers
      reporting nine original studies met the selection criteria. One was a randomized
      controlled trial (RCT), one a retrospective nested case-control study, five were
      retrospective cohort studies of which one was linked with a case-control study,
      and one was a retrospective population-based analysis. Outcomes associated with
      treatment with statins included decreased all-cause mortality in three out of
      four studies (OR/HR 0.48-0.67 in three studies, OR 0.99 in one study), decreased
      COPD-related mortality (OR 0.19-0.29), reduction in incidence of respiratory
      related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer
      intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary
      function. The RCT reported improvement in exercise capacity and dyspnea after
      exercise associated with decreased levels of C-reactive protein and Interleukin-6
      in statin users, but no improvement of lung function. CONCLUSION: There is
      evidence from observational studies and one RCT that statins may reduce morbidity
      and/or mortality in COPD patients. Further interventional studies are required to
      confirm these findings.

PMID- 19594890
TI  - Epidemiology and risk factors for Staphylococcus aureus colonization in children
      in the post-PCV7 era.
AB  - BACKGROUND: The incidence of community-associated methicillin-resistant
      Staphylococcus aureus (MRSA) has risen dramatically in the U.S., particularly
      among children. Although Streptococcus pneumoniae colonization has been inversely
      associated with S. aureus colonization in unvaccinated children, this and other
      risk factors for S. aureus carriage have not been assessed following widespread
      use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were
      to (1) determine the prevalence of S. aureus and MRSA colonization in young
      children in the context of widespread use of PCV7; and (2) examine risk factors
      for S. aureus colonization in the post-PCV7 era, including the absence of vaccine
      type S. pneumoniae colonization. METHODS: Swabs of the anterior nares (S. aureus)
      were obtained from children enrolled in an ongoing study of nasopharyngeal
      pneumococcal colonization of healthy children in 8 Massachusetts communities.
      Children 3 months to <7 years of age seen for well child or sick visits in
      primary care offices from 11/03-4/04 and 10/06-4/07 were enrolled. S. aureus was
      identified and antibiotic susceptibility testing was performed. Epidemiologic
      risk factors for S. aureus colonization were collected from parent surveys and
      chart reviews, along with data on pneumococcal colonization. Multivariate mixed
      model analyses were performed to identify factors associated with S. aureus
      colonization. RESULTS: Among 1,968 children, the mean age (SD) was 2.7 (1.8)
      years, 32% received an antibiotic in the past 2 months, 2% were colonized with
      PCV7 strains and 24% were colonized with non-PCV7 strains. The prevalence of S.
      aureus colonization remained stable between 2003-04 and 2006-07 (14.6% vs.
      14.1%), while MRSA colonization remained low (0.2% vs. 0.9%, p = 0.09). Although
      absence of pneumococcal colonization was not significantly associated with S.
      aureus colonization, age (6-11 mo vs. > or =5 yrs, OR 0.39 [95% CI 0.24-0.64]; 1
      1.99 yrs vs. > or =5 yrs, OR 0.35 [0.23-0.54]; 2-2.99 yrs vs. > or =5 yrs, OR
      0.45 [0.28-0.73]; 3-3.99 yrs vs. > or =5 yrs, OR 0.53 [0.33-0.86]) and recent
      antibiotic use were significant predictors in multivariate models. CONCLUSION: In
      Massachusetts, S. aureus and MRSA colonization remained stable from 2003-04 to
      2006-07 among children <7 years despite widespread use of pneumococcal conjugate
      vaccine. S. aureus nasal colonization varies by age and is inversely correlated
      with recent antibiotic use.

PMID- 19594894
TI  - The Nordic maintenance care program: case management of chiropractic patients
      with low back pain--defining the patients suitable for various management
      strategies.
AB  - BACKGROUND: Maintenance care is a well known concept among chiropractors,
      although there is little knowledge about its exact definition, its indications
      and usefulness. As an initial step in a research program on this phenomenon, it
      was necessary to identify chiropractors' rationale for their use of maintenance
      care. Previous studies have identified chiropractors' choices of case management
      strategies in response to different case scenarios. However, the rationale for
      these management strategies is not known. In other words, when presented with
      both the case, and different management strategies, there was consensus on how to
      match these, but if only the management strategies were provided, would
      chiropractors be able to define the cases to fit these strategies? The objective
      with this study was to investigate if there is a common pattern in Finnish
      chiropractors' case management of patients with low back pain (LBP), with special
      emphasis on long-term treatment. METHODS: Information was obtained in a
      structured workshop. Fifteen chiropractors, members of the Finnish Chiropractors'
      Union, and present at the general assembly, participated throughout the entire
      workshop session. These were divided into five teams each consisting of 3 people.
      A basic case of a patient with low back pain was presented together with six
      different management strategies undertaken after one month of treatment. Each
      team was then asked to describe one (or several) suitable case(s) for each of the
      six strategies, based on the aspects of 1) symptoms/findings, 2) the low back
      pain history in the past year, and 3) other observations. After each session the
      people in the groups were changed. Responses were collected as key words on flip
      over boards. These responses were grouped and counted. RESULTS: There appeared to
      be consensus among the participants in relation to the rationale for at least
      four of the management strategies and partial consensus on the rationale for the
      remaining two. In relation to maintenance care, the patient's past history was
      important but also the doctor-patient relationship. CONCLUSION: These results
      confirm that there is a pattern among Nordic chiropractors in how they manage
      patients with LBP. More information is needed to define the "cut-point" for the
      indication of prolonged care.

PMID- 19594892
TI  - A novel role of HLA class I in the pathology of medulloblastoma.
AB  - BACKGROUND: MHC class I expression by cancer cells enables specific antigen
      recognition by the immune system and protection of the host. However, in some
      cancer types MHC class I expression is associated with an unfavorable outcome. We
      explored the basis of MHC class I association with unfavorable prognostic marker
      expression in the case of medulloblastoma. METHODS: We investigated expression of
      four essential components of MHC class I (heavy chain, beta2m, TAP1 and TAP2) in
      10 medulloblastoma mRNA samples, a tissue microarray containing 139
      medulloblastoma tissues and 3 medulloblastoma cell lines. Further, in
      medulloblastoma cell lines we evaluated the effects of HLA class I engagement on
      activation of ERK1/2 and migration in vitro. RESULTS: The majority of specimens
      displayed undetectable or low levels of the heavy chains. Medulloblastomas
      expressing high levels of HLA class I displayed significantly higher levels of
      anaplasia and c-myc expression, markers of poor prognosis. Binding of beta2m or a
      specific antibody to open forms of HLA class I promoted phosphorylation of ERK1/2
      in medulloblastoma cell line with high levels, but not in the cell line with low
      levels of HLA heavy chain. This treatment also promoted ERK1/2 activation
      dependent migration of medulloblastoma cells. CONCLUSION: MHC class I expression
      in medulloblastoma is associated with anaplasia and c-myc expression, markers of
      poor prognosis. Peptide- and/or beta2m-free forms of MHC class I may contribute
      to a more malignant phenotype of medulloblastoma by modulating activation of
      signaling molecules such as ERK1/2 that stimulates cell mobility.

PMID- 19594893
TI  - Inflammatory parameters predict etiologic patterns but do not allow for
      individual prediction of etiology in patients with CAP: results from the German
      competence network CAPNETZ.
AB  - BACKGROUND: Aim of this study was to evaluate the correlation of inflammatory
      markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC)
      with microbiological etiology of CAP. METHODS: We enrolled 1337 patients (62 +/-
      18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In
      all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were
      classified according to microbial diagnosis and CRB-65 score. RESULTS: In
      patients with typical bacterial CAP, levels of PCT, CRP and WBC were
      significantly higher compared to CAP of atypical or viral etiology. There were no
      significant differences in PCT, CRP and WBC in patients with atypical or viral
      etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity
      of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for
      discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI
      0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65,
      PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison
      to outpatients. CONCLUSION: PCT, CRP and WBC are highest in typical bacterial
      etiology in CAP but do not allow individual prediction of etiology. In contrast
      to CRP and WBC, PCT is useful in severity assessment of CAP.

PMID- 19594895
TI  - Health, ageing and private health insurance: baseline results from the 45 and Up
      Study cohort.
AB  - BACKGROUND: This study investigates the relationships between health and
      lifestyle factors, age and private health insurance (PHI) in a large Australian
      population-based cohort study of people aged 45 years and over; the 45 and Up
      Study. Unlike previous Australian analyses of relationships between health,
      lifestyle and PHI, it incorporates adjustment for multiple confounding
      socioeconomic and demographic factors. Recruitment into the 45 and Up Study began
      in February 2006 and these analyses relate to the first 103,042 participants who
      joined the study prior to July 2008. RESULTS: The proportion with PHI decreased
      with increasing age. The factors independently and most strongly associated with
      having PHI were: higher income; higher educational attainment; not holding a
      health care concession card; not being of Aboriginal/Torres Strait Islander
      origin; being a non-smoker; high levels of self-rated health and functional
      capacity; and low levels of psychological distress. These factors increased the
      probability of having PHI by 16% to 125%, compared to individuals without these
      characteristics. PHI coverage was significantly but only marginally higher in
      people reporting non-melanoma skin cancer (adjusted RR 1.04, 95%CI 1.03-1.05),
      prostate cancer (1.09, 1.06-1.11) or an enlarged prostate (1.07, 1.06-1.09),
      those reporting a family history of a range of conditions (e.g. 1.02, 1.01-1.03
      for a family history of heart disease; 1.03, 1.02-1.04 for a family history of
      prostate cancer) and lower in people reporting diabetes (0.92, 0.91-0.94) or
      stroke (0.91, 0.88-0.94), compared to people who did not have these medical or
      family histories. PHI was higher in those reporting certain surgical procedures
      with RRs (95%CI) of 1.12 (1.09-1.15) for hip replacement, 1.10 (1.08-1.13) for
      knee replacement and 1.12 (1.09-1.15) for prostatectomy, compared to those not
      reporting these interventions. CONCLUSION: Compared to the rest of the study
      population, those with PHI are richer, better educated, more health conscious, in
      better health and more likely to use certain discretionary health services.
      Hence, PHI use is generally highest among those with the least need for health
      care. Whether or not people have PHI is more strongly associated with demographic
      and lifestyle factors than with health status.

PMID- 19594896
TI  - Sexual selection on cuticular hydrocarbons in the Australian field cricket,
      Teleogryllus oceanicus.
AB  - BACKGROUND: Females in a wide range of taxa have been shown to base their choice
      of mates on pheromone signals. However, little research has focussed specifically
      on the form and intensity of selection that mate choice imposes on the pheromone
      signal. Using multivariate selection analysis, we characterise directly the form
      and intensity of sexual selection acting on cuticular hydrocarbons, chemical
      compounds widely used in the selection of mates in insects. Using the Australian
      field cricket Teleogryllus oceanicus as a model organism, we use three measures
      of male attractiveness to estimate fitness; mating success, the duration of
      courtship required to elicit copulation, and subsequent spermatophore attachment
      duration. RESULTS: We found that all three measures of male attractiveness
      generated sexual selection on male cuticular hydrocarbons, however there were
      differences in the form and intensity of selection among these three measures.
      Mating success was the only measure of attractiveness that imposed both
      univariate linear and quadratic selection on cuticular hydrocarbons. Although we
      found that all three attractiveness measures generated nonlinear selection, again
      only mating success was found to exert statistically significant stabilizing
      selection. CONCLUSION: This study shows that sexual selection plays an important
      role in the evolution of male cuticular hydrocarbon signals.

PMID- 19594897
TI  - Gene expression responses in male fathead minnows exposed to binary mixtures of
      an estrogen and antiestrogen.
AB  - BACKGROUND: Aquatic organisms are continuously exposed to complex mixtures of
      chemicals, many of which can interfere with their endocrine system, resulting in
      impaired reproduction, development or survival, among others. In order to analyze
      the effects and mechanisms of action of estrogen/anti-estrogen mixtures, we
      exposed male fathead minnows (Pimephales promelas) for 48 hours via the water to
      2, 5, 10, and 50 ng 17alpha-ethinylestradiol (EE2)/L, 100 ng ZM 189,154/L (a
      potent antiestrogen known to block activity of estrogen receptors) or mixtures of
      5 or 50 ng EE(2)/L with 100 ng ZM 189,154/L. We analyzed gene expression changes
      in the gonad, as well as hormone and vitellogenin plasma levels. RESULTS:
      Steroidogenesis was down-regulated by EE(2) as reflected by the reduced plasma
      levels of testosterone in the exposed fish and down-regulation of genes in the
      steroidogenic pathway. Microarray analysis of testis of fathead minnows treated
      with 5 ng EE(2)/L or with the mixture of 5 ng EE(2)/L and 100 ng ZM 189,154/L
      indicated that some of the genes whose expression was changed by EE(2) were
      blocked by ZM 189,154, while others were either not blocked or enhanced by the
      mixture, generating two distinct expression patterns. Gene ontology and pathway
      analysis programs were used to determine categories of genes for each expression
      pattern. CONCLUSION: Our results suggest that response to estrogens occurs via
      multiple mechanisms, including canonical binding to soluble estrogen receptors,
      membrane estrogen receptors, and other mechanisms that are not blocked by pure
      antiestrogens.

PMID- 19594899
TI  - A comparison of baseline methodologies for 'Reducing Emissions from Deforestation
      and Degradation'.
AB  - BACKGROUND: A mechanism for emission reductions from deforestation and
      degradation (REDD) is very likely to be included in a future climate agreement.
      The choice of REDD baseline methodologies will crucially influence the
      environmental and economic effectiveness of the climate regime. We compare three
      different historical baseline methods and one innovative dynamic model baseline
      approach to appraise their applicability under a future REDD policy framework
      using a weighted multi-criteria analysis. RESULTS: The results show that each
      baseline method has its specific strengths and weaknesses. Although the dynamic
      model allows for the best environmental and for comparatively good economic
      performance, its high demand for data and technical capacity limit the current
      applicability in many developing countries. CONCLUSION: The adoption of a multi
      tier approach will allow countries to select the baseline method best suiting
      their specific capabilities and data availability while simultaneously ensuring
      scientific transparency, environmental effectiveness and broad political support.

PMID- 19594898
TI  - Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics
      of early stage breast cancer.
AB  - BACKGROUND: Mass spectrometric analysis of the blood proteome is an emerging
      method of clinical proteomics. The approach exploiting multi-protein/peptide sets
      (fingerprints) detected by mass spectrometry that reflect overall features of a
      specimen's proteome, termed proteome pattern analysis, have been already shown in
      several studies to have applicability in cancer diagnostics. We aimed to identify
      serum proteome patterns specific for early stage breast cancer patients using
      MALDI-ToF mass spectrometry. METHODS: Blood samples were collected before the
      start of therapy in a group of 92 patients diagnosed at stages I and II of the
      disease, and in a group of age-matched healthy controls (104 women). Serum
      specimens were purified and the low-molecular-weight proteome fraction was
      examined using MALDI-ToF mass spectrometry after removal of albumin and other
      high-molecular-weight serum proteins. Protein ions registered in a mass range
      between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created
      in our group, which included modeling spectra as a sum of Gaussian bell-shaped
      curves. RESULTS: We have identified features of serum proteome patterns that were
      significantly different between blood samples of healthy individuals and early
      stage breast cancer patients. The classifier built of three spectral components
      that differentiated controls and cancer patients had 83% sensitivity and 85%
      specificity. Spectral components (i.e., protein ions) that were the most frequent
      in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a
      biomarker built from these three components showed 88% sensitivity and 78%
      specificity). Of note, we did not find a significant correlation between features
      of serum proteome patterns and established prognostic or predictive factors like
      tumor size, nodal involvement, histopathological grade, estrogen and progesterone
      receptor expression. In addition, we observed a significantly (p = 0.0003)
      increased level of osteopontin in blood of the group of cancer patients studied
      (however, the plasma level of osteopontin classified cancer samples with 88%
      sensitivity but only 28% specificity). CONCLUSION: MALDI-ToF spectrometry of
      serum has an obvious potential to differentiate samples between early breast
      cancer patients and healthy controls. Importantly, a classifier built on MS-based
      serum proteome patterns outperforms available protein biomarkers analyzed in
      blood by immunoassays.

PMID- 19594900
TI  - DHEA-dependent and organ-specific regulation of TNF-alpha mRNA expression in a
      murine polymicrobial sepsis and trauma model.
AB  - INTRODUCTION: Dehydroepiandrosterone (DHEA) improves survival after trauma and
      sepsis, while mechanisms of action are not yet fully understood. Therefore, we
      investigated the influence of DHEA on local cytokine expression in a two-hit
      model. METHODS: Male NMRI mice were subjected to femur fracture/hemorrhagic shock
      and subsequent sepsis. Sham-operated animals were used as controls. DHEA (25
      mg/kg) or vehicle was administered daily. Mortality rate, activity and body
      temperature were determined daily after sepsis induction. TNF-alpha, IL-1beta and
      IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48
      and 96 hours. RESULTS: DHEA treatment resulted in a significantly reduced
      mortality rate and improvements in the clinical status. On cytokine level, only
      TNF-alpha was significantly reduced in the cecal ligation and puncture (CLP)
      vehicle group in both tissues after 48 hours. This suppression could be restored
      by DHEA administration. In contrast, after 96 hours, TNF-alpha was up-regulated
      in the CLP-vehicle group while remaining moderate by DHEA treatment in liver
      tissue. CONCLUSIONS: The improved outcome after DHEA treatment and trauma is
      coherent with restoration of TNF-alpha in liver and lung after 48 hours and a
      counter-regulatory attenuation of TNF-alpha in liver after 96 hours. Thus, DHEA
      seems to act, time and organ dependent, as a potent modulator of TNF-alpha
      expression.

PMID- 19594903
TI  - Conceptualising spirituality for medical research and health service provision.
AB  - The need to take account of spirituality in research and health services
      provision is assuming ever greater importance. However the field has long been
      hampered by a lack of conceptual clarity about the nature of spirituality itself.
      We do not agree with the sceptical claim that it is impossible to conceptualize
      spirituality within a scientific paradigm. Our aims are to 1) provide a brief
      over-view of critical thinking that might form the basis for a useful definition
      of spirituality for research and clinical work and 2) demystify the language of
      spirituality for clinical practice and research.

PMID- 19594901
TI  - Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of
      Helicobacter pylori.
AB  - BACKGROUND: Contamination of endoscopy equipment by Helicobacter pylori (H.
      pylori) frequently occurs after endoscopic examination of H. pylori-infected
      patients. In the hospital, manual pre-cleaning and soaking in glutaraldehyde is
      an important process to disinfect endoscopes. However, this might not be
      sufficient to remove H. pylori completely, and some glutaraldehyde-resistant
      bacteria might survive and be passed to the next patient undergoing endoscopic
      examination through unidentified mechanisms. We identified an Imp/OstA protein
      associated with glutaraldehyde resistance in a clinical strain, NTUH-C1, from our
      previous study. To better understand and manage the problem of glutaraldehyde
      resistance, we further investigated its mechanism. RESULTS: The minimal
      inhibitory concentrations (MICs) of glutaraldehyde andexpression of imp/ostA RNA
      in 11 clinical isolates from the National Taiwan University Hospital were
      determined. After glutaraldehyde treatment, RNA expression in the strains with
      the MICs of 4-10 microg/ml was higher than that in strains with the MICs of 1-3
      microg/ml. We examined the full-genome expression of strain NTUH-S1 after
      glutaraldehyde treatment using a microarray and found that 40 genes were
      upregulated and 31 genes were downregulated. Among the upregulated genes,
      imp/ostA and msbA, two putative lipopolysaccharide biogenesis genes, were
      selected for further characterization. The sensitivity to glutaraldehyde or
      hydrophobic drugs increased in both of imp/ostA and msbA single mutants. The
      imp/ostA and msbA double mutant was also hypersensitive to these chemicals. The
      lipopolysaccharide contents decreased in individual imp/ostA and msbA mutants and
      dramatically reduced in the imp/ostA and msbA double mutant. Outer membrane
      permeability assay demonstrated that the imp/ostA and msbA double mutation
      resulted in the increase of outer membrane permeability. Ethidium bromide
      accumulation assay demonstrated that MsbA was involved in efflux of hydrophobic
      drugs. CONCLUSION: The expression levels of imp/ostA and msbA were correlated
      with glutaraldehyde resistance in clinical isolates after glutaraldehyde
      treatment. Imp/OstA and MsbA play a synergistic role in hydrophobic drugs
      resistance and lipopolysaccharide biogenesis in H. pylori.

PMID- 19594904
TI  - Chronic exposure to outdoor air pollution and diagnosed cardiovascular disease:
      meta-analysis of three large cross-sectional surveys.
AB  - BACKGROUND: Higher exposure to outdoor air pollution is associated with increased
      cardiopulmonary deaths, but there is limited evidence about the association
      between outdoor air pollution and diagnosed cardiovascular disease. Our study
      aimed to estimate the size of the association between long term exposure to
      outdoor air pollution and prevalent cardiovascular disease. METHODS: We carried
      out a cross-sectional analysis of data on more than 19,000 white adults aged 45
      and older who participated in three representative surveys of the English
      population in 1994, 1998 and 2003, examining the relationship between self
      reported doctor-diagnosed cardiovascular disease and exposure to outdoor air
      pollutants using multilevel regression techniques and meta-analysis. RESULTS: The
      combined estimates suggested that an increase of 1 microg m-3 in concentration of
      particulate matter less than 10 microns in diameter was associated with an
      increase of 2.9% (95% CI -0.6% to 6.5%) in prevalence of cardiovascular disease
      in men, and an increase of 1.6% (95%CI -2.1% to 5.5%) in women. The year-specific
      analyses showed strongly positive associations in 2003 between odds of
      cardiovascular disease in both men and women and exposure to particulate matter
      but not in 1994 or 1998. We found no consistent associations between exposure to
      gaseous air pollutants and doctor-diagnosed cardiovascular disease. CONCLUSION:
      The associations of prevalent cardiovascular disease with concentration of
      particulate matter less than 10 microns in diameter, while only weakly positive,
      were consistent with the effects reported in cohort studies. The results provide
      evidence of the size of the association between particulate air pollution and the
      prevalence of cardiovascular disease but no evidence for an association with
      gaseous pollutants. We found strongly positive associations between particulate
      matter and cardiovascular disease in 2003 only, which highlights the importance
      of replicating findings in more than one population.

PMID- 19594905
TI  - Genomic evidence for non-random endemic populations of decaying exons from
      mammalian genes.
AB  - BACKGROUND: Functional diversification of genes in mammalian genomes is
      engendered by a number of processes, e.g., gene duplication and alternative
      splicing. Gene duplication is classically discussed as leading to
      neofunctionalization (generation of new functions), subfunctionalization
      (generation of a varied function), or pseudogenization (loss of the gene and its
      function). RESULTS: Here, we focus on the process of pseudogenization, but
      specifically for individual exons from genes. It is at present unclear to what
      extent pseudogenization of individual exon duplications affects gene evolution,
      i.e., is it a random phenomenon, or is it associated with specific types of genes
      and encoded proteins, and positions in gene structures? We gathered genomic
      evidence for pseudogenic exons (PsiEs, i.e., exons disabled by frameshifts and
      premature stop codons), to examine for significant trends in their distribution
      across four mammalian genomes (specifically human, cow, mouse and rat). Across
      these four genomes, we observed a consistent population of PsiEs, associated with
      0.4-1.0% of genes. These PsiE populations exhibit codon substitution patterns
      that are typical of an endemic population of decaying sequences. In human, PsiEs
      have significant over-representation for functional categories related to 'ion
      binding' and 'nucleic-acid binding', compared to duplicated exons in general.
      Also, PsiEs tend to be associated with some protein domains that are abundant
      generally, e.g., Zinc-finger and immunoglobulin protein domains, but not others,
      e.g., EGF-like domains. Positionally, PsiEs are also significantly associated
      with the 5' end of genes, but despite this, individual stop codons are positioned
      so that there is significant avoidance of potential targeting to nonsense
      mediated decay. In human, PsiEs are often associated with alternative splicing
      (in 22 out of 284 genes with PsiEs in their milieu), and can have different parts
      of their sequence differentially spliced in alternative transcripts. Some unusual
      cases of PsiEs embedded within 5' and 3' non-coding exons are observed.
      CONCLUSION: Our results indicate the types of genes that harbour PsiEs, and
      demonstrate that PsiEs have non-random distribution within gene structures. These
      PsiEs may function in gene regulation through generation of transcribed
      pseudogenes, or regulatory alternate transcripts.

PMID- 19594906
TI  - Alcohol use among university students in Sweden measured by an electronic
      screening instrument.
AB  - BACKGROUND: Electronic-based alcohol screening and brief interventions for
      university students with problem drinking behaviours forms an important means by
      which to identify risky drinkers. METHODS: In this study an e-SBI project was
      implemented to assess drinking patterns, and to provide personalised feedback
      about alcohol consumption and related health problems, to students in a Swedish
      university. In this study, third semester university students (n = 2858) from all
      faculties (colleges) at the University were invited to participate in e-SBI
      screenings. This study employed a randomised controlled trial, with respondents
      having a equal chance of being assigned to a limited, or full-feedback response.
      RESULTS: The study shows that high risk drinkers tend to underestimate their own
      consumption compared to others, and that these high risk drinkers experience more
      negative consequences after alcohol intake, than other respondents. There was a
      strong belief, for both high- and low-risk drinkers, that alcohol helped
      celebrations be more festive. This study also confirms findings from other study
      locations that while males drank more than females in our study population;
      females reached the same peak alcohol blood concentrations as males. CONCLUSION:
      Obtaining clear and current information on drinking patterns demonstrated by
      university students can help public health officials, university administration,
      and local health care providers develop appropriate prevention and treatment
      strategies.

PMID- 19594907
TI  - Head & neck optical diagnostics: vision of the future of surgery.
AB  - Review paper and Proceedings of the Inaugural Meeting of the Head and Neck
      Optical Diagnostics Society (HNODS) on March 14th 2009 at University College
      London. The aim of our research must be to provide breakthrough translational
      research which can be applied clinically in the immediate rather than the near
      future. We are fortunate that this is indeed a possibility and may fundamentally
      change current clinical and surgical practice to improve our patients' lives.

PMID- 19594908
TI  - Cardiotoxicity of Freon among refrigeration services workers: comparative cross
      sectional study.
AB  - BACKGROUND: Freon includes a number of gaseous, colorless chlorofluorocarbons.
      Although freon is generally considered to be a fluorocarbon of relatively low
      toxicity; significantly detrimental effects may occur upon over exposure. The
      purpose of the present study is to investigate whether occupational exposure to
      fluorocarbons can induce arterial hypertension, myocardial ischemia, cardiac
      arrhythmias, elevated levels of plasma lipids and renal dysfunction. METHODS:
      This comparative cross-sectional study was conducted at the cardiology clinic of
      the Suez Canal Authority Hospital (Egypt). The study included 23 apparently
      healthy male workers at the refrigeration services workshop who were exposed to
      fluorocarbons (FC 12 and FC 22) and 23 likewise apparently healthy male workers
      (unexposed), the control group. All the participants were interviewed using a pre
      composed questionnaire and were subjected to a clinical examination and relevant
      laboratory investigations. RESULTS: There were no significant statistical
      differences between the groups studied regarding symptoms suggesting arterial
      hypertension and renal affection, although a significantly higher percentage of
      the studied refrigeration services workers had symptoms of arrhythmias. None of
      the workers had symptoms suggesting coronary artery disease. Clinical examination
      revealed that the refrigeration services workers had a significantly higher mean
      pulse rate compared to the controls, though no significant statistical
      differences were found in arterial blood pressure measurements between the two
      study groups. Exercise stress testing of the workers studied revealed normal
      heart reaction to the increased need for oxygen, while sinus tachycardia was
      detected in all the participants. The results of Holter monitoring revealed
      significant differences within subject and group regarding the number of abnormal
      beats detected throughout the day of monitoring (p < 0.001). There were no
      significant differences detected in the average heart rate during the monitoring
      period within subject or group. Most laboratory investigations revealed absence
      of significant statistical differences for lipid profile markers, serum
      electrolyte levels and glomerular lesion markers between the groups except for
      cholesterol and urinary beta2-microglobulin (tubular lesion markers) levels which
      were significantly elevated in freon exposed workers. CONCLUSIONS: Unprotected
      occupational exposure to chlorofluorocarbons can induce cardiotoxicity in the
      form of cardiac arrhythmias. The role of chlorofluorocarbons in inducing arterial
      hypertension and coronary artery diseases is unclear, although significantly
      elevated serum cholesterol and urinary beta2-microglobulin levels raise a
      concern.

PMID- 19594909
TI  - Construction and use of gene expression covariation matrix.
AB  - BACKGROUND: One essential step in the massive analysis of transcriptomic profiles
      is the calculation of the correlation coefficient, a value used to select pairs
      of genes with similar or inverse transcriptional profiles across a large fraction
      of the biological conditions examined. Until now, the choice between the two
      available methods for calculating the coefficient has been dictated mainly by
      technological considerations. Specifically, in analyses based on double-channel
      techniques, researchers have been required to use covariation correlation, i.e.
      the correlation between gene expression changes measured between several pairs of
      biological conditions, expressed for example as fold-change. In contrast, in
      analyses of single-channel techniques scientists have been restricted to the use
      of coexpression correlation, i.e. correlation between gene expression levels. To
      our knowledge, nobody has ever examined the possible benefits of using
      covariation instead of coexpression in massive analyses of single channel
      microarray results. RESULTS: We describe here how single-channel techniques can
      be treated like double-channel techniques and used to generate both gene
      expression changes and covariation measures. We also present a new method that
      allows the calculation of both positive and negative correlation coefficients
      between genes. First, we perform systematic comparisons between two given
      biological conditions and classify, for each comparison, genes as increased (I),
      decreased (D), or not changed (N). As a result, the original series of n gene
      expression level measures assigned to each gene is replaced by an ordered string
      of n(n-1)/2 symbols, e.g. IDDNNIDID....DNNNNNNID, with the length of the string
      corresponding to the number of comparisons. In a second step, positive and
      negative covariation matrices (CVM) are constructed by calculating statistically
      significant positive or negative correlation scores for any pair of genes by
      comparing their strings of symbols. CONCLUSION: This new method, applied to four
      different large data sets, has allowed us to construct distinct covariation
      matrices with similar properties. We have also developed a technique to translate
      these covariation networks into graphical 3D representations and found that the
      local assignation of the probe sets was conserved across the four chip set models
      used which encompass three different species (humans, mice, and rats). The
      application of adapted clustering methods succeeded in delineating six conserved
      functional regions that we characterized using Gene Ontology information.

PMID- 19594910
TI  - Reactivation from latency displays HIV particle budding at plasma membrane,
      accompanying CD44 upregulation and recruitment.
AB  - BACKGROUND: It has been accepted that HIV buds from the cell surface in T
      lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent
      studies, on the other hand, suggest that HIV preferentially buds from the cell
      surface even in monocytic cells. However, most studies are based on observations
      in acutely infected cells and little is known about HIV budding concomitant with
      reactivation from latency. Such studies would provide a better understanding of a
      reservoir for HIV. RESULTS: We observed HIV budding in latently infected T
      lymphocytic and monocytic cell lines following TNF-alpha stimulation and examined
      the upregulation of host factors that may be involved in particle production.
      Electron microscopy analysis revealed that reactivation of latently infected J1.1
      cells (latently infected Jurkat cells with HIV-1) and U1 cells (latently infected
      U937 cells with HIV-1) displayed HIV particle budding predominantly at the plasma
      membrane, a morphology that is similar to particle budding in acutely infected
      Jurkat and U937 cells. When mRNA expression levels were quantified by qRT-PCR, we
      found that particle production from reactivated J1.1 and U1 cells was accompanied
      by CD44 upregulation. This upregulation was similarly observed when Jurkat and
      U937 cells were acutely infected with HIV-1 but not when just stimulated with TNF
      alpha, suggesting that CD44 upregulation was linked with HIV production but not
      with cell stimulation. The molecules in endocytic pathways such as CD63 and HRS
      were also upregulated when U1 cells were reactivated and U937 cells were acutely
      infected with HIV-1. Confocal microscopy revealed that these upregulated host
      molecules were recruited to and accumulated at the sites where mature particles
      were formed at the plasma membrane. CONCLUSION: Our study indicates that HIV
      particles are budded at the plasma membrane upon reactivation from latency, a
      morphology that is similar to particle budding in acute infection. Our data also
      suggest that HIV expression may lead to the upregulation of certain host cell
      molecules that are recruited to sites of particle assembly, possibly coordinating
      particle production.

PMID- 19594911
TI  - Metabolic profiling of Parkinson's disease: evidence of biomarker from gene
      expression analysis and rapid neural network detection.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder. The
      diagnosis of Parkinsonism is challenging because currently none of the clinical
      tests have been proven to help in diagnosis. PD may produce characteristic
      perturbations in the metabolome and such variations can be used as the marker for
      detection of disease. To test this hypothesis, we used proton NMR and
      multivariate analysis followed by neural network pattern detection. METHODS &
      RESULTS: 1H nuclear magnetic resonance spectroscopy analysis was carried out on
      plasma samples of 37 healthy controls and 43 drug-naive patients with PD. Focus
      on 22 targeted metabolites, 17 were decreased and 5 were elevated in PD patients
      (p < 0.05). Partial least squares discriminant analysis (PLS-DA) showed that
      pyruvate is the key metabolite, which contributes to the separation of PD from
      control samples. Furthermore, gene expression analysis shows significant (p <
      0.05) change in expression of PDHB and NPFF genes leading to increased pyruvate
      concentration in blood plasma. Moreover, the implementation of 1H- NMR spectral
      pattern in neural network algorithm shows 97.14% accuracy in the detection of
      disease progression. CONCLUSION: The results increase the prospect of a robust
      molecular definition in detection of PD through the early symptomatic phase of
      the disease. This is an ultimate opening for therapeutic intervention. If
      validated in a genuinely prospective fashion in larger samples, the biomarker
      trajectories described here will go a long way to facilitate the development of
      useful therapies. Moreover, implementation of neural network will be a
      breakthrough in clinical screening and rapid detection of PD.

PMID- 19594912
TI  - Determinants of mortality in non-neutropenic ICU patients with candidaemia.
AB  - INTRODUCTION: Candidaemia in critically-ill intensive care unit (ICU) patients is
      associated with high crude mortality. Determinants of mortality--particularly
      those amenable to potential modification--are incompletely defined. METHODS: A
      nationwide prospective clinical and microbiological cohort study of all episodes
      of ICU-acquired candidaemia occurring in non-neutropenic adults was undertaken in
      Australian ICUs between 2001 and 2004. Multivariate Cox regression analyses were
      performed to determine independently significant variables associated with
      mortality. RESULTS: 183 episodes of ICU-acquired candidaemia occurred in 183
      patients during the study period. Of the 179 with microbiological data, Candida
      albicans accounted for 111 (62%) episodes and Candida glabrata, 32 (18%). Outcome
      data were available for 173: crude hospital mortality at 30 days was 56%. Host
      factors (older age, ICU admission diagnosis, mechanical ventilation and ICU
      admission diagnosis) and failure to receive systemic antifungal therapy were
      significantly associated with mortality on multivariate analysis. Among the
      subset who received initial fluconazole therapy (n = 93), the crude mortality was
      52%. Host factors (increasing age and haemodialysis receipt), but not organism-
      (Candida species, fluconazole MIC), pharmacokinetic- (fluconazole dose, time to
      initiation), or pharmacodynamic-related parameters (fluconazole dose:MIC ratio)
      were associated with mortality. Process of care measures advocated in recent
      guidelines were implemented inconsistently: follow-up blood cultures were
      obtained in 68% of patients, central venous catheters removed within five days in
      80% and ophthalmological examination performed in 36%. CONCLUSIONS: Crude
      mortality remains high in Australian ICU patients with candidaemia and is
      overwhelmingly related to host factors but not treatment variables (the time to
      initiation of antifungals or fluconazole pharmacokinetic and pharmacodynamic
      factors). The role and timing of early antifungal intervention in critically-ill
      ICU patients requires further investigation.

PMID- 19594913
TI  - Standardised assessment of patients' capacity to manage medications: a systematic
      review of published instruments.
AB  - BACKGROUND: Older people are commonly prescribed complex multi-drug regimens
      while also experiencing declines in the cognitive and physical abilities required
      for medication management, leading to increased risk of medication errors and
      need for assisted living. The purpose of this study was to review published
      instruments designed to assess patients' capacity to self-administer medications.
      METHODS: Searches of Medline, EMBASE, CINAHL, PsycINFO, International
      Pharmaceutical Abstracts, Health and Psychosocial Instruments, Google, and
      reference lists of identified publications were conducted to identify English
      language articles describing development and validation of instruments designed
      to assess patients' capacity to self-administer medications. Methodological
      quality of validation studies was rated independently against published criteria
      by two reviewers and reliability and validity data were reviewed. RESULTS: Thirty
      two instruments were identified, of which 14 met pre-defined inclusion criteria.
      Instruments fell into two categories: those that used patients' own medications
      as the basis for assessment and those that used a simulated medication regimen.
      The quality of validation studies was generally low to moderate and few
      instruments were subjected to reliability testing. Most instruments had some
      evidence of construct validity, through associations with tests of cognitive
      function, health literacy, activities of daily living or measures of medication
      management or adherence. Only one instrument had sensitivity and specificity data
      with respect to prediction of medication-related outcomes such as adherence to
      therapy. Only three instruments had validity data from more than one independent
      research group. CONCLUSION: A number of performance-based instruments exist to
      assess patients' capacity to manage their own medications. These may be useful
      for identifying physical and cognitive barriers to successful medication
      management, but further studies are needed to determine whether they are able to
      accurately and reliably predict medication outcomes.

PMID- 19594915
TI  - Application of molecular cytogenetic techniques to clarify apparently balanced
      complex chromosomal rearrangements in two patients with an abnormal phenotype:
      case report.
AB  - BACKGROUND: Complex chromosomal rearrangements (CCR) are rare cytogenetic
      findings that are difficult to karyotype by conventional cytogenetic analysis
      partially because of the relative low resolution of this technique. High
      resolution genotyping is necessary in order to identify cryptic imbalances, for
      instance near the multiple breakpoints, to explain the abnormal phenotype in
      these patients. We applied several molecular techniques to elucidate the
      complexity of the CCRs of two adult patients with abnormal phenotypes. RESULTS:
      Multicolour fluorescence in situ hybridization (M-FISH) showed that in patient 1
      the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for
      patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array
      analysis uncovered a deletion in chromosome region 10p13 for patient 1,
      harbouring 17 genes, while patient 2 showed no pathogenic gains or losses.
      Additional FISH analysis with locus specific BAC-probes was performed, leading to
      the identification of cryptic interstitial structural rearrangements in both
      patients. CONCLUSION: Application of M-FISH and SNP-array analysis to apparently
      balanced CCRs is useful to delineate the complex chromosomal rearrangement in
      detail. However, it does not always identify cryptic imbalances as an explanation
      for the abnormal phenotype in patients with a CCR.

PMID- 19594914
TI  - Thoracic epidural anesthesia reverses sepsis-induced hepatic hyperperfusion and
      reduces leukocyte adhesion in septic rats.
AB  - INTRODUCTION: Liver dysfunction is a common feature of severe sepsis and is
      associated with a poor outcome. Both liver perfusion and hepatic inflammatory
      response in sepsis might be affected by sympathetic nerve activity. However, the
      effects of thoracic epidural anesthesia (TEA), which is associated with regional
      sympathetic block, on septic liver injury are unknown. Therefore, we investigated
      hepatic microcirculation and inflammatory response during TEA in septic rats.
      METHODS: Forty-five male Sprague-Dawley-rats were instrumented with thoracic
      epidural catheters and randomized to receive a sham procedure (Sham), cecal
      ligation and puncture (CLP) without epidural anesthesia (Sepsis) and CLP with
      epidural infusion of 15 ul/h bupivacaine 0.5% (Sepsis + TEA). All animals
      received 2 ml/100 g/h NaCl 0.9%. In 24 (n = 8 in each group) rats, sinusoidal
      diameter, loss of sinusoidal perfusion and sinusoidal blood flow as well as
      temporary and permanent leukocyte adhesion to sinusoidal and venolar endothelium
      were recorded by intravital microscopy after 24 hours. In 21 (n = 7 in each
      group) separate rats, cardiac output was measured by thermodilution. Blood
      pressure, heart rate, serum transaminase activity, serum TNF-alpha concentration
      and histologic signs of tissue injury were recorded. RESULTS: Whereas cardiac
      output remained constant in all groups, sinusoidal blood flow increased in the
      Sepsis group and was normalized in rats subjected to sepsis and TEA. Sepsis
      induced sinusoidal vasoconstriction was not ameliorated by TEA. In the Sepsis +
      TEA group, the increase in temporary venolar leukocyte adherence was blunted. In
      contrast to this, sinusoidal leukocyte adherence was not ameliorated in the
      Sepsis + TEA group. Sepsis-related release of TNF-alpha and liver tissue injury
      were not affected by Sepsis + TEA. CONCLUSIONS: This study demonstrates that TEA
      reverses sepsis-induced alterations in hepatic perfusion and ameliorates hepatic
      leukocyte recruitment in sepsis.

PMID- 19594916
TI  - The role of pharmacists in developing countries: the current scenario in
      Pakistan.
AB  - During the past few years, the pharmacy profession has expanded significantly in
      terms of professional services delivery and now has been recognized as an
      important profession in the multidisciplinary provision of health care. In
      contrast to the situation in developed countries, pharmacists in developing
      countries are still underutilized and their role as health care professionals is
      not deemed important by either the community or other health care providers. The
      aim of this paper is to highlight the role of pharmacists in developing
      countries, particularly in Pakistan. The paper draws on the literature related to
      the socioeconomic and health status of Pakistan's population, along with
      background on the pharmacy profession in the country in the context of the
      current directions of health care. The paper highlights the current scenario and
      portrays the pharmacy profession in Pakistan. It concludes that although the
      pharmacy profession in Pakistan is continuously evolving, the health care system
      of Pakistan has yet to recognize the pharmacist's role. This lack of recognition
      is due to the limited interaction of pharmacists with the public. Pharmacists in
      Pakistan are concerned about their present professional role in the health care
      system. The main problem they are facing is the shortage of pharmacists in
      pharmacies. Moreover, their services are focused towards management more than
      towards customers. For these reasons, the pharmacist's role as a health care
      professional is not familiar to the public.

PMID- 19594918
TI  - Predicting performance using background characteristics of international medical
      graduates in an inner-city university-affiliated Internal Medicine residency
      training program.
AB  - BACKGROUND: IMGs constitute about a third of the United States (US) internal
      medicine graduates. US residency training programs face challenges in selection
      of IMGs with varied background features. However data on this topic is limited.
      We analyzed whether any pre-selection characteristics of IMG residents in our
      internal medicine program are associated with selected outcomes, namely
      competency based evaluation, examination performance and success in acquiring
      fellowship positions after graduation. METHODS: We conducted a retrospective
      study of 51 IMGs at our ACGME accredited teaching institution between 2004 and
      2007. Background resident features namely age, gender, self-reported ethnicity,
      time between medical school graduation to residency (pre-hire time), USMLE step I
      & II clinical skills scores, pre-GME clinical experience, US externship and
      interest in pursuing fellowship after graduation expressed in their personal
      statements were noted. Data on competency-based evaluations, in-service exam
      scores, research presentation and publications, fellowship pursuance were
      collected. There were no fellowships offered in our hospital in this study
      period. Background features were compared between resident groups according to
      following outcomes: (a) annual aggregate graduate PGY-level specific competency
      based evaluation (CBE) score above versus below the median score within our
      program (scoring scale of 1 - 10), (b) US graduate PGY-level specific resident in
      training exam (ITE) score higher versus lower than the median score, and (c)
      those who succeeded to secure a fellowship within the study period. Using
      appropriate statistical tests & adjusted regression analysis, odds ratio with 95%
      confidence intervals were calculated. RESULTS: 94% of the study sample were IMGs;
      median age was 35 years (Inter-Quartile range 25th - 75th percentile (IQR): 33-37
      years); 43% women and 59% were Asian physicians. The median pre-hire time was 5
      years (IQR: 4-7 years) and USMLE step I & step II clinical skills scores were 85
      (IQR: 80-88) & 82 (IQR: 79-87) respectively. The median aggregate CBE scores
      during training were: PG1 5.8 (IQR: 5.6-6.3); PG2 6.3 (IQR 6-6.8) & PG3 6.7 (IQR:
      6.7 - 7.1). 25% of our residents scored consistently above US national median ITE
      scores in all 3 years of training and 16% pursued a fellowship.Younger residents
      had higher aggregate annual CBE score than the program median (p < 0.05). Higher
      USMLE scores were associated with higher than US median ITE scores, reflecting
      exam-taking skills. Success in acquiring a fellowship was associated with
      consistent fellowship interest (p < 0.05) and research publications or
      presentations (p <0.05). None of the other characteristics including visa status
      were associated with the outcomes. CONCLUSION: Background IMG features namely,
      age and USMLE scores predict performance evaluation and in-training examination
      scores during residency training. In addition enhanced research activities during
      residency training could facilitate fellowship goals among interested IMGs.

PMID- 19594917
TI  - Burnout and use of HIV services among health care workers in Lusaka District,
      Zambia: a cross-sectional study.
AB  - BACKGROUND: Well-documented shortages of health care workers in sub-Saharan
      Africa are exacerbated by the increased human resource demands of rapidly
      expanding HIV care and treatment programmes. The successful continuation of
      existing programmes is threatened by health care worker burnout and HIV-related
      illness. METHODS: From March to June 2007, we studied occupational burnout and
      utilization of HIV services among health providers in the Lusaka public health
      sector. Providers from 13 public clinics were given a 36-item, self-administered
      questionnaire and invited for focus group discussions and key-informant
      interviews. RESULTS: Some 483 active clinical staff completed the questionnaire
      (84% response rate), 50 staff participated in six focus groups, and four
      individuals gave interviews. Focus group participants described burnout as
      feeling overworked, stressed and tired. In the survey, 51% reported occupational
      burnout. Risk factors were having another job (RR 1.4 95% CI 1.2-1.6) and knowing
      a co-worker who left in the last year (RR 1.6 95% CI 1.3-2.2). Reasons for co
      worker attrition included: better pay (40%), feeling overworked or stressed
      (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV
      testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last
      year. In contrast, discussion groups perceived low testing rates. Both discussion
      groups and survey respondents identified confidentiality as the prime reason for
      not undergoing HIV testing. CONCLUSION: In Lusaka primary care clinics, overwork,
      illness and death were common reasons for attrition. Programmes to improve
      access, acceptability and confidentiality of health care services for clinical
      providers and to reduce workplace stress could substantially affect workforce
      stability.

PMID- 19594919
TI  - Early effect of a single intravenous injection of ethanol on hepatic sinusoidal
      endothelial fenestrae in rabbits.
AB  - BACKGROUND: It has been postulated that ethanol affects hepatic sinusoidal and
      perisinusoidal cells. In the current experimental study, we investigated the
      early effect of a single intravenous dose of ethanol on the diameter of liver
      sinusoidal endothelial fenestrae in New Zealand White rabbits. The diameter of
      fenestrae in these rabbits is similar to the diameter found in humans with
      healthy livers. The effect of ethanol on the size of fenestrae was studied using
      transmission electron microscopy, because plastic embedding provides true
      measures for the diameter of fenestrae. RESULTS: After intravenous administration
      of a single dose of 0.75 g/kg, ethanol concentration peaked at 1.1 +/- 0.10 g/l
      at ten minutes after injection. Compared to control rabbits (103 +/- 1.1 nm; n =
      8), the average diameter of fenestrae in ethanol-injected rabbits determined at
      10 minutes after injection was significantly (p < 0.01) smaller (96 +/- 2.2 nm; n
      = 5). Detailed analysis of distribution histograms of the diameters of fenestrae
      showed that the effect of ethanol was highly homogeneous. CONCLUSION: A decrease
      of the diameter of fenestrae 10 minutes after ethanol administration is likely
      the earliest morphological alteration induced by ethanol in the liver and
      underscores the potential role of liver sinusoidal endothelial cells in alcoholic
      liver injury.

PMID- 19594920
TI  - Zwanzig-Mori projection operators and EEG dynamics: deriving a simple equation of
      motion.
AB  - We present a macroscopic theory of electroencephalogram (EEG) dynamics based on
      the laws of motion that govern atomic and molecular motion. The theory is an
      application of Zwanzig-Mori projection operators. The result is a simple equation
      of motion that has the form of a generalized Langevin equation (GLE), which
      requires knowledge only of macroscopic properties. The macroscopic properties can
      be extracted from experimental data by one of two possible variational
      principles. These variational principles are our principal contribution to the
      formalism. Potential applications are discussed, including applications to the
      theory of critical phenomena in the brain, Granger causality and Kalman
      filters.PACS code: 87.19.lj.

PMID- 19594922
TI  - Employment and sociodemographic characteristics: a study of increasing precarity
      in the health districts of Belo Horizonte, Brazil.
AB  - BACKGROUND: The fundamental importance of human resources for the development of
      health care systems is recognized the world over. Health districts, which
      constitute the middle level of the municipal health care system in the city of
      Belo Horizonte, Brazil, deal with demands from all parts of the system. This
      research seeks to provide the essential features required in order to understand
      the phenomenon of increase in precarity of employment in these health districts.
      METHODS: The legal and human resource management documents used by the Municipal
      Health Secretariat of the City of Belo Horizonte were adopted as the corpus for
      this research. In order to analyse the changes in employment (2002-2006), the
      data were collected from ArteRH, a computerized database dealing specifically
      with data related to human resources, which began operating in 2001. The workers
      were classified into permanent and non-permanent groups, and their contractual
      rights were described. Employment dynamics and changes were examined,
      concentrating on the incorporation of workers and on their social and employment
      rights during the period under study. The comparative data for the two groups
      obtained were presented in frequency distribution tables according to type of
      employment, sex, age group, level of education and wages from 2002 to 2006.
      RESULTS: There was a clear difference between the permanent worker and non
      permanent worker groups as regards existing guaranteed employment rights and
      social security. The increase in the number of non-permanent workers in the
      workforce, the growing proportion of older workers among the permanently employed
      and the real wage reductions during the period from 2002 to 2006 are indicative
      of the process of growing precarity of employment in the group studied.
      CONCLUSION: It is a plausible supposition that the demand for health reforms,
      along with the legal limits imposed on financial expenditure, gave rise to the
      new types of contract and the present employment situation in the health
      districts in Belo Horizonte.

PMID- 19594921
TI  - Adequate use of asthma inhalation medication in children: more involvement of the
      parents seems useful.
AB  - BACKGROUND: Asthma and other chronic airway diseases can be effectively treated
      by inhaler therapy. Inhaler therapy depends on appropriate use of the inhaler.
      This study evaluates the knowledge among Dutch children and their parents
      regarding asthma inhaler therapy and appropriateness of its use. FINDINGS: Five
      general practices selected all children aged 0 to 12 years on asthma inhalation
      medication. Children demonstrated inhaler use and were interviewed with their
      parents.46 subjects were enrolled; mean age 5.5 years (SD 3.4) years; 26 (57%)
      were boys. Of the children using one inhaler only, 70% used the inhaler as
      indicated and of those using more than one inhaler 46%. On average 2.6 mistakes
      were made during demonstration of the technique, and 2 mistakes were reported in
      the interview. In total, 87% of the parents decided when and how the inhaler had
      to be used. Spacer cleaning was performed correctly by 49%; 26% reported a
      correct way of assessing how many doses were remaining. CONCLUSION: Dutch
      children make essential mistakes related to inhaler use that are easy to avoid.
      We recommend a better explanation and demonstration of the technique, and
      recommend involvement of the parents during instruction.

PMID- 19594923
TI  - DNA-binding by Haemophilus influenzae and Escherichia coli YbaB, members of a
      widely-distributed bacterial protein family.
AB  - BACKGROUND: Genes orthologous to the ybaB loci of Escherichia coli and
      Haemophilus influenzae are widely distributed among eubacteria. Several years
      ago, the three-dimensional structures of the YbaB orthologs of both E. coli and
      H. influenzae were determined, revealing a novel "tweezer"-like structure.
      However, a function for YbaB had remained elusive, with an early study of the H.
      influenzae ortholog failing to detect DNA-binding activity. Our group recently
      determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding
      protein. To reconcile those results, we assessed the abilities of both the H.
      influenzae and E. coli YbaB proteins to bind DNA to which B. burgdorferi EbfC can
      bind. RESULTS: Both the H. influenzae and the E. coli YbaB proteins bound to
      tested DNAs. DNA-binding was not well competed with poly-dI-dC, indicating some
      sequence preferences for those two proteins. Analyses of binding characteristics
      determined that both YbaB orthologs bind as homodimers. Different DNA sequence
      preferences were observed between H. influenzae YbaB, E. coli YbaB and B.
      burgdorferi EbfC, consistent with amino acid differences in the putative DNA
      binding domains of these proteins. CONCLUSION: Three distinct members of the
      YbaB/EbfC bacterial protein family have now been demonstrated to bind DNA.
      Members of this protein family are encoded by a broad range of bacteria,
      including many pathogenic species, and results of our studies suggest that all
      such proteins have DNA-binding activities. The functions of YbaB/EbfC family
      members in each bacterial species are as-yet unknown, but given the ubiquity of
      these DNA-binding proteins among Eubacteria, further investigations are
      warranted.

PMID- 19594924
TI  - Magnetic resonance imaging (MRI) has failed to distinguish between smaller gut
      regions and larger haemal sinuses in sea urchins (Echinodermata: Echinoidea).
AB  - A response to Ziegler A, Faber C, Mueller S, Bartolomaeus T: Systematic
      comparison and reconstruction of sea urchin (Echinoidea) internal anatomy: a
      novel approach using magnetic resonance imaging. BMC Biol 2008, 6: 33.

PMID- 19594926
TI  - A structured review of reasons for ecstasy use and related behaviours: pointers
      for future research.
AB  - BACKGROUND: While the health risks of using ecstasy warrant intervention
      development, a recent meta-analysis of determinants of ecstasy use identified a
      number of lacunae in the literature. Specifically, no studies were included that
      address behaviours other than 'using ecstasy' (e.g. 'trying out ecstasy' or
      'ceasing ecstasy use'). However, because meta-analyses aim to integrate study
      results quantitatively, the resulting rigid exclusion criteria cause many studies
      to be discarded on the basis of their qualitative methodology. Such qualitative
      studies may nonetheless provide valuable insights to guide future research. To
      provide an overview of these insights regarding ecstasy use, the current study
      summarizes and combines what is known from qualitative and exploratory
      quantitative literature on ecstasy use. METHODS: The databases PsycINFO and
      MedLine were searched for publications reporting reasons for ecstasy use and
      related behaviour, and the results were structured and discussed per behaviour
      and compared over behaviours. RESULTS: Two main categories of reasons were found.
      The first category comprised reasons to start using ecstasy, use ecstasy, use
      ecstasy more often, and refrain from ceasing ecstasy use. The second category
      comprised reasons to refrain from starting to use ecstasy, use less ecstasy, and
      cease using ecstasy. Reasons for related behaviours within each of these two
      categories appear to differ, but not as substantially as between the two
      categories. A large number of reasons that were not yet explored in quantitative
      research emerged. CONCLUSION: The current summary and combination of exploratory
      studies yields useful lists of reasons for each behaviour. Before these lists can
      inform interventions, however, they beg quantitative verification. Also,
      similarity of determinant configurations of different behaviours can be assessed
      by addressing determinants of several behaviours in one study. Another important
      finding is that meta-analytical integration of the literature may overlook
      important findings and implications. Thus, qualitative reviews remain useful
      instruments in setting the research agenda.

PMID- 19594925
TI  - Dosage compensation on the active X chromosome minimizes transcriptional noise of
      X-linked genes in mammals.
AB  - BACKGROUND: Theory predicts that haploid-expressed genes should have noisier
      expression than comparable diploid-expressed ones with the same expression level.
      However, in mammals there are several classes of gene that are monoallelically
      expressed, including X-linked genes, imprinted genes and some other autosomal
      genes. Does it follow that the evolution of X chromosomes in eukaryotes comes at
      the cost of increased transcriptional noise in the heterogametic sex? Moreover,
      is escaping X-inactivation in mammalian females associated with an increase in
      transcriptional variation? To address these questions, we analyze gene expression
      variation between replicate samples of diverse mammalian cell lines in steady
      state using microarray data. RESULTS: We observe that transcriptional variation
      of X-linked genes is no different to that of autosomal genes both before and
      after control for transcript abundance. By contrast, autosomal genes subject to
      allelic exclusion do have unusually high noise levels even allowing for their low
      transcript abundance. The prior theory we suggest was insufficient, at least as
      regards X-chromosomes, as it failed to appreciate the regulatory complexity of
      gene expression, not least the effects of genomic neighborhood. CONCLUSIONS:
      These results suggest that high noise is not a necessary consequence of haploid
      expression and emphasize the primacy of expression level as a determinant of
      noise. The latter has consequences for understanding the etiology of haplo
      insufficiency and the evolution of gene expression levels. Given the coupling
      between expression level and noise on the X-chromosome, we suggest that part of
      the selective advantage of dosage compensation is noise abatement of X-linked
      genes.

PMID- 19594927
TI  - Computer vision for microscopy diagnosis of malaria.
AB  - This paper reviews computer vision and image analysis studies aiming at automated
      diagnosis or screening of malaria infection in microscope images of thin blood
      film smears. Existing works interpret the diagnosis problem differently or
      propose partial solutions to the problem. A critique of these works is furnished.
      In addition, a general pattern recognition framework to perform diagnosis, which
      includes image acquisition, pre-processing, segmentation, and pattern
      classification components, is described. The open problems are addressed and a
      perspective of the future work for realization of automated microscopy diagnosis
      of malaria is provided.

PMID- 19594928
TI  - Spatio-temporal cluster analysis of county-based human West Nile virus incidence
      in the continental United States.
AB  - BACKGROUND: West Nile virus (WNV) is a vector-borne illness that can severely
      affect human health. After introduction on the East Coast in 1999, the virus
      quickly spread and became established across the continental United States.
      However, there have been significant variations in levels of human WNV incidence
      spatially and temporally. In order to quantify these variations, we used
      Kulldorff's spatial scan statistic and Anselin's Local Moran's I statistic to
      uncover spatial clustering of human WNV incidence at the county level in the
      continental United States from 2002-2008. These two methods were applied with
      varying analysis thresholds in order to evaluate sensitivity of clusters
      identified. RESULTS: The spatial scan and Local Moran's I statistics revealed
      several consistent, important clusters or hot-spots with significant year-to-year
      variation. In 2002, before the pathogen had spread throughout the country, there
      were significant regional clusters in the upper Midwest and in Louisiana and
      Mississippi. The largest and most consistent area of clustering throughout the
      study period was in the Northern Great Plains region including large portions of
      Nebraska, South Dakota, and North Dakota, and significant sections of Colorado,
      Wyoming, and Montana. In 2006, a very strong cluster centered in southwest Idaho
      was prominent. Both the spatial scan statistic and the Local Moran's I statistic
      were sensitive to the choice of input parameters. CONCLUSION: Significant spatial
      clustering of human WNV incidence has been demonstrated in the continental United
      States from 2002-2008. The two techniques were not always consistent in the
      location and size of clusters identified. Although there was significant inter
      annual variation, consistent areas of clustering, with the most persistent and
      evident being in the Northern Great Plains, were demonstrated. Given the wide
      variety of mosquito species responsible and the environmental conditions they
      require, further spatio-temporal clustering analyses on a regional level is
      warranted.

PMID- 19594929
TI  - Acute effects of a thermogenic nutritional supplement on cycling time to
      exhaustion and muscular strength in college-aged men.
AB  - BACKGROUND: The purpose of the present study was to examine the acute effects of
      a thermogenic nutritional supplement containing caffeine, capsaicin, bioperine,
      and niacin on muscular strength and endurance performance. METHODS: Twenty
      recreationally-active men (mean +/- SD age = 21.5 +/- 1.4 years; stature = 178.2
      +/- 6.3 cm; mass = 76.5 +/- 9.9 kg; VO2 PEAK = 3.05 +/- 0.59 L/min-1) volunteered
      to participate in this randomized, double-blinded, placebo-controlled, cross-over
      study. All testing took place over a three-week period, with each of the 3
      laboratory visits separated by 7 days (+/- 2 hours). During the initial visit, a
      graded exercise test was performed on a Lode Corival cycle ergometer (Lode,
      Groningen, Netherlands) until exhaustion (increase of 25 W every 2 min) to
      determine the maximum power output (W) at the VO2 PEAK (Parvo Medics TrueOne(R)
      2400 Metabolic Measurement System, Sandy, Utah). In addition, one-repetition
      maximum (1-RM) strength was assessed using the bench press (BP) and leg press
      (LP) exercises. During visits 2 and 3, the subjects were asked to consume a
      capsule containing either the active supplement (200 mg caffeine, 33.34 mg
      capsaicin, 5 mg bioperine, and 20 mg niacin) or the placebo (175 mg of calcium
      carbonate, 160 mg of microcrystalline cellulose, 5 mg of stearic acid, and 5 mg
      of magnesium stearate in an identical capsule) 30 min prior to the testing.
      Testing included a time-to-exhaustion (TTE) ride on a cycle ergometer at 80% of
      the previously-determined power output at VO2 PEAK followed by 1-RM LP and BP
      tests. RESULTS: There were no differences (p > 0.05) between the active and
      placebo trials for BP, LP, or TTE. However, for the BP and LP scores, the
      baseline values (visit 1) were less than the values recorded during visits 2 and
      3 (p </= 0.05). CONCLUSION: Our findings indicated that the active supplement
      containing caffeine, capsaicin, bioperine, and niacin did not alter muscular
      strength or cycling endurance when compared to a placebo trial. The lack of
      increases in BP and LP strength and cycle ergometry endurance elicited by this
      supplement may have been related to the relatively small dose of caffeine, the
      high intensity of exercise, the untrained status of the participants, and/or the
      potential for caffeine and capsaicin to increase carbohydrate oxidation.

PMID- 19594930
TI  - Variation in gene duplicates with low synonymous divergence in Saccharomyces
      cerevisiae relative to Caenorhabditis elegans.
AB  - BACKGROUND: The direct examination of large, unbiased samples of young gene
      duplicates in their early stages of evolution is crucial to understanding the
      origin, divergence and preservation of new genes. Furthermore, comparative
      analysis of multiple genomes is necessary to determine whether patterns of gene
      duplication can be generalized across diverse lineages or are species-specific.
      Here we present results from an analysis comprising 68 duplication events in the
      Saccharomyces cerevisiae genome. We partition the yeast duplicates into ohnologs
      (generated by a whole-genome duplication) and non-ohnologs (from small-scale
      duplication events) to determine whether their disparate origins commit them to
      divergent evolutionary trajectories and genomic attributes. RESULTS: We conclude
      that, for the most part, ohnologs tend to appear remarkably similar to non
      ohnologs in their structural attributes (specifically the relative composition
      frequencies of complete, partial and chimeric duplicates), the discernible length
      of the duplicated region (duplication span) as well as genomic location.
      Furthermore, we find notable differences in the features of S. cerevisiae gene
      duplicates relative to those of another eukaryote, Caenorhabditis elegans, with
      respect to chromosomal location, extent of duplication and the relative
      frequencies of complete, partial and chimeric duplications. CONCLUSIONS: We
      conclude that the variation between yeast and worm duplicates can be attributed
      to differing mechanisms of duplication in conjunction with the varying efficacy
      of natural selection in these two genomes as dictated by their disparate
      effective population sizes.

PMID- 19594932
TI  - A strategy for constructing aneuploid yeast strains by transient nondisjunction
      of a target chromosome.
AB  - BACKGROUND: Most methods for constructing aneuploid yeast strains that have
      gained a specific chromosome rely on spontaneous failures of cell division
      fidelity. In Saccharomyces cerevisiae, extra chromosomes can be obtained when
      errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown
      occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that
      does not require such spontaneous failures. The method combines two well
      characterized genetic tools: a conditional centromere that transiently blocks
      disjunction of one specific chromosome, and a duplication marker assay that
      identifies disomes among daughter cells. To test the strategy, we targeted
      chromosomes III, IV, and VI for duplication. RESULTS: The centromere of each
      chromosome was replaced by a centromere that can be blocked by growth in
      galactose, and ura3::HIS3, a duplication marker. Transient exposure to galactose
      induced the appearance of colonies carrying duplicated markers for chromosomes
      III or IV, but not VI. Microarray-based comparative genomic hybridization (CGH)
      confirmed that disomic strains carrying extra chromosome III or IV were
      generated. Chromosome VI contains several genes that are known to be deleterious
      when overexpressed, including the beta-tubulin gene TUB2. To test whether a
      tubulin stoichiometry imbalance is necessary for the apparent lethality caused by
      an extra chromosome VI, we supplied the parent strain with extra copies of the
      alpha-tubulin gene TUB1, then induced nondisjunction. Galactose-dependent
      chromosome VI disomes were produced, as revealed by CGH. Some chromosome VI
      disomes also carried extra, unselected copies of additional chromosomes.
      CONCLUSION: This method causes efficient nondisjunction of a targeted chromosome
      and allows resulting disomic cells to be identified and maintained. We used the
      method to test the role of tubulin imbalance in the apparent lethality of disomic
      chromosome VI. Our results indicate that a tubulin imbalance is necessary for
      disomic VI lethality, but it may not be the only dosage-dependent effect.

PMID- 19594933
TI  - Factors associated with improved survival among older colorectal cancer patients
      in the US: a population-based analysis.
AB  - BACKGROUND: The purpose of this study was to estimate the relative impact of
      changes in demographics, stage at detection, treatment mix, and medical
      technology on 5-year survival among older colorectal cancer (CRC) patients.
      METHODS: We selected older patients diagnosed with CRC between 1992 and 2000 from
      the SEER-Medicare database and followed them through 2005. Trends in demographic
      characteristics, stage at detection and initial treatment mix were evaluated
      descriptively. Separate multivariate logistic regression models for colon (CC)
      and rectal cancer (RC) patients were estimated to isolate the independent effects
      of these factors along with technological change (proxied by cohort year) on 5
      year survival. RESULTS: Our sample included 37,808 CC and 13,619 RC patients
      (combined mean +/- SD age: 77.2 +/- 7.0 years; 55% female; 87% white). In recent
      years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV,
      and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC
      and RC patients diagnosed in later years were slightly older with somewhat better
      Charlson scores and were more likely to be female, from the Northeast, and from
      areas with higher average education levels. Surgery alone was more common in
      later years for CC patients while combined surgery, chemotherapy, and
      radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year
      observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to
      42.2% for RC patients. Multivariate logistic regressions indicate that patients
      diagnosed in 2000 had significantly greater odds of 5-year survival than those
      diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC). Our decomposition suggests that
      early detection had little impact on survival; rather, technological improvements
      (e.g., new medical technologies or more effective use of existing technologies)
      and changing demographics were responsible for the largest share of the change in
      5-year survival in CC and RC between 1992 and 2000. CONCLUSION: Technological
      advances and changes in patient demographics had the largest impact on improved
      colorectal cancer survival during the study period.

PMID- 19594931
TI  - A systematic review of post-deployment injury-related mortality among military
      personnel deployed to conflict zones.
AB  - BACKGROUND: This paper reports on a systematic review of the literature on the
      post-conflict injury-related mortality of service members who deployed to
      conflict zones. METHODS: Literature databases, reference lists of articles,
      agencies, investigators, and other sources were examined to find studies
      comparing injury-related mortality of military veterans who had served in
      conflict zones with that of contemporary veterans who had not served in conflict
      zones. Injury-related mortality was defined as a cause of death indicated by
      International Classification of Diseases E-codes E800 to E999 (external causes)
      or subgroupings within this range of codes. RESULTS: Twenty studies met the
      review criteria; all involved veterans serving during either the Vietnam or
      Persian Gulf conflict. Meta-analysis indicated that, compared with non-conflict
      zone veterans, injury-related mortality was elevated for veterans serving in
      Vietnam (summary mortality rate ratio (SMRR) = 1.26, 95% confidence interval
      (95%CI) = 1.08-1.46) during 9 to 18 years of follow-up. Similarly, injury-related
      mortality was elevated for veterans serving in the Persian Gulf War (SMRR = 1.26,
      95%CI = 1.16-1.37) during 3 to 8 years of follow-up. Much of the excess mortality
      among conflict-zone veterans was associated with motor vehicle events. The excess
      mortality decreased over time. Hypotheses to account for the excess mortality in
      conflict-zone veterans included post-traumatic stress, coping behaviors such as
      substance abuse, ill-defined diseases and symptoms, lower survivability in injury
      events due to conflict-zone comorbidities, altered perceptions of risk, and/or
      selection processes leading to the deployment of individuals who were risk
      takers. CONCLUSION: Further research on the etiology of the excess mortality in
      conflict-zone veterans is warranted to develop appropriate interventions.

PMID- 19594934
TI  - Nest expansion assay: a cancer systems biology approach to in vitro invasion
      measurements.
AB  - BACKGROUND: Traditional in vitro cell invasion assays focus on measuring one cell
      parameter at a time and are often less than ideal in terms of reproducibility and
      quantification. Further, many techniques are not suitable for quantifying the
      advancing margin of collectively migrating cells, arguably the most important
      area of activity during tumor invasion. We have developed and applied a highly
      quantitative, standardized, reproducible Nest Expansion Assay (NEA) to measure
      cancer cell invasion in vitro, which builds upon established wound-healing
      techniques. This assay involves creating uniform circular "nests" of cells within
      a monolayer of cells using a stabilized, silicone-tipped drill press, and
      quantifying the margin expansion into an overlaid extracellular matrix (ECM)-like
      component using computer-assisted applications. FINDINGS: The NEA was applied to
      two human-derived breast cell lines, MCF10A and MCF10A-CA1d, which exhibit
      opposite degrees of tumorigenicity and invasion in vivo. Assays were performed to
      incorporate various microenvironmental conditions, in order to test their
      influence on cell behavior and measures. Two types of computer-driven image
      analysis were performed using Java's freely available ImageJ software and its
      FracLac plugin to capture nest expansion and fractal dimension, respectively -
      which are both taken as indicators of invasiveness. Both analyses confirmed that
      the NEA is highly reproducible, and that the ECM component is key in defining
      invasive cell behavior. Interestingly, both analyses also detected significant
      differences between non-invasive and invasive cell lines, across various
      microenvironments, and over time. CONCLUSION: The spatial nature of the NEA makes
      its outcome susceptible to the global influence of many cellular parameters at
      once (e.g., motility, protease secretion, cell-cell adhesion). We propose the NEA
      as a mid-throughput technique for screening and simultaneous examination of
      factors contributing to cancer cell invasion, particularly suitable for
      parameterizing and validating Cancer Systems Biology approaches such as
      mathematical modeling.

PMID- 19594935
TI  - Children's vomiting following posterior fossa surgery: A retrospective study.
AB  - BACKGROUND: Nausea and vomiting is a problem for children after neurosurgery and
      those requiring posterior fossa procedures appear to have a high incidence. This
      clinical observation has not been quantified nor have risk factors unique to this
      group of children been elucidated. METHODS: A six year retrospective chart audit
      at two Canadian children's hospitals was conducted. The incidence of nausea and
      vomiting was extracted. Hierarchical multivariable logistic regression was used
      to quantify risk and protective factors at 120 hours after surgery and early vs.
      late vomiting. RESULTS: The incidence of vomiting over a ten day postoperative
      period was 76.7%. Documented vomiting ranged from single events to greater than
      20 over the same period. In the final multivariable model: adolescents (age 12 to
      <17) were less likely to vomit by 120 hours after surgery than other age groups;
      those who received desflurane, when compared to all other volatile anesthetics,
      were more likely to vomit, yet the use of ondansetron with desflurane decre
      kelihood. Children who had intraoperative ondansetron were more likely to vomit
      in the final multivariable model (perhaps because of its use, in the clinical
      judgment of the anesthesiologist, for children considered at risk). Children who
      started vomiting in the first 24 hours were more likely to be school age (groups
      4 to <7 and 7 to <12) and receive desflurane. Nausea was not well documented and
      was therefore not analyzed. CONCLUSION: The incidence of vomiting in children
      after posterior fossa surgery is sufficient to consider all children requiring
      these procedures to be at high risk for POV. Nausea requires better assessment
      and documentation.

PMID- 19594936
TI  - Sequence and structural analysis of the Asp-box motif and Asp-box beta
      propellers; a widespread propeller-type characteristic of the Vps10 domain family
      and several glycoside hydrolase families.
AB  - BACKGROUND: The Asp-box is a short sequence and structure motif that folds as a
      well-defined beta-hairpin. It is present in different folds, but occurs most
      prominently as repeats in beta-propellers. Asp-box beta-propellers are known to
      be characteristically irregular and to occur in many medically important
      proteins, most of which are glycosidase enzymes, but they are otherwise not well
      characterized and are only rarely treated as a distinct beta-propeller family. We
      have analyzed the sequence, structure, function and occurrence of the Asp-box and
      s-Asp-box -a related shorter variant, and provide a comprehensive classification
      and computational analysis of the Asp-box beta-propeller family. RESULTS: We find
      that all conserved residues of the Asp-box support its structure, whereas the
      residues in variable positions are generally used for other purposes. The Asp-box
      clearly has a structural role in beta-propellers and is highly unlikely to be
      involved in ligand binding. Sequence analysis of the Asp-box beta-propeller
      family reveals it to be very widespread especially in bacteria and suggests a
      wide functional range. Disregarding the Asp-boxes, sequence conservation of the
      propeller blades is very low, but a distinct pattern of residues with specific
      properties have been identified. Interestingly, Asp-boxes are occasionally found
      very close to other propeller-associated repeats in extensive mixed-motif
      stretches, which strongly suggests the existence of a novel class of hybrid beta
      propellers. Structural analysis reveals that the top and bottom faces of Asp-box
      beta-propellers have striking and consistently different loop properties; the
      bottom is structurally conserved whereas the top shows great structural
      variation. Interestingly, only the top face is used for functional purposes in
      known structures. A structural analysis of the 10-bladed beta-propeller fold,
      which has so far only been observed in the Asp-box family, reveals that the inner
      strands of the blades are unusually far apart, which explains the surprisingly
      large diameter of the central tunnel of sortilin. CONCLUSION: We have provided
      new insight into the structure and function of the Asp-box motif and of Asp-box
      beta-propellers, and expect that the classification and analysis presented here
      will prove helpful in interpreting future data on Asp-box proteins in general and
      on Asp-box beta-propellers in particular.

PMID- 19594937
TI  - Long-term safety of mometasone furoate administered via a dry powder inhaler in
      children: Results of an open-label study comparing mometasone furoate with
      beclomethasone dipropionate in children with persistent asthma.
AB  - BACKGROUND: To assess the long-term pediatric safety of 2 doses of mometasone
      furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate
      persistent asthma and compare them with that of beclomethasone dipropionate
      administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent
      asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100
      microg once-daily (QD) for children aged 4-11 years. METHODS: Children (N = 233)
      aged 4-11 years were randomized to 52 weeks of treatment with MF-DPI 200 microg
      QD AM, MF-DPI 100 microg twice daily (BID), or BDP-MDI 168 microg BID. Patients
      had used inhaled corticosteroids (ICSs) daily for > or = 30 days before the
      screening visit and were on stable ICS doses for > or = 2 weeks before screening.
      The primary safety variable was the incidence of adverse events. Secondary safety
      variables were laboratory tests (including cortisol concentrations), vital signs,
      and physical examination. RESULTS: The incidence of adverse events was similar in
      all 3 treatment groups. The most frequently reported adverse event was upper
      respiratory tract infection, reported by 47%-49% of the MF-DPI-treated patients
      and 51% of the BPD-treated patients. Most adverse events were considered
      unrelated to study drug. The most frequently reported related adverse events were
      headache (MF-DPI 200 microg QD AM, 8%; MF-DPI 100 microg BID, 4%; BDP-MDI 168
      microg BID, 2%) and oral candidiasis (4% in each treatment group). No clinically
      relevant changes in laboratory values, including plasma cortisol, vital signs, or
      physical examinations were noted in any treatment group. CONCLUSION: Both MF-DPI
      doses were well tolerated, with no unusual or unexpected adverse events or safety
      concerns, and had a similar adverse event profile to that of BDP-MDI 168 microg
      BID.

PMID- 19594938
TI  - Development of SSR markers and analysis of diversity in Turkish populations of
      Brachypodium distachyon.
AB  - BACKGROUND: Brachypodium distachyon (Brachypodium) is rapidly emerging as a
      powerful model system to facilitate research aimed at improving grass crops for
      grain, forage and energy production. To characterize the natural diversity of
      Brachypodium and provide a valuable new tool to the growing list of resources
      available to Brachypodium researchers, we created and characterized a large,
      diverse collection of inbred lines. RESULTS: We developed 84 inbred lines from
      eight locations in Turkey. To enable genotypic characterization of this
      collection, we created 398 SSR markers from BAC end and EST sequences. An
      analysis of 187 diploid lines from 56 locations with 43 SSR markers showed
      considerable genotypic diversity. There was some correlation between SSR
      genotypes and broad geographic regions, but there was also a high level of
      genotypic diversity at individual locations. Phenotypic analysis of this new
      germplasm resource revealed considerable variation in flowering time, seed size,
      and plant architecture. The inbreeding nature of Brachypodium was confirmed by an
      extremely high level of homozygosity in wild plants and a lack of cross
      pollination under laboratory conditions. CONCLUSION: Taken together, the
      inbreeding nature and genotypic diversity observed at individual locations
      suggest a significant amount of long-distance seed dispersal. The resources
      developed in this study are freely available to the research community and will
      facilitate experimental applications based on natural diversity.

PMID- 19594940
TI  - Occupational kneeling and radiographic tibiofemoral and patellofemoral
      osteoarthritis.
AB  - BACKGROUND: The objective of our study was to evaluate the association between
      occupational kneeling and compartment specific radiographic tibiofemoral (TF) and
      patellofemoral (PF) osteoarthritis (OA). METHODS: Questionnaire data and
      bilateral knee radiographs were obtained in 134 male floor layers and 120 male
      graphic designers (referents). Weight-bearing radiographs in three views (postero
      anterior, lateral and axial) were classified according to joint space narrowing.
      After the exclusion of subjects with reports of earlier knee injuries the odds
      ratio (OR) with 95% confidence intervals (CI) of TF and PF OA was computed among
      floor layers compared to graphic designers in three age groups (</= 49; 50-59;
      >/= 60 years). Using logistic regression, estimates were adjusted for body mass
      index and knee-straining sports. In addition, the association between trade
      seniority and TF OA was assessed in age-adjusted test for trend analyses.
      RESULTS: The prevalence of TF OA was significantly higher among floor layers aged
      50-59 years compared to graphic designers (OR = 3.6, 95% CI = 1.1-12.0) while non
      significant estimates were found in the young and elderly age groups.
      Furthermore, the adjusted OR of TF OA increased with trade seniority among floor
      layers (test for trend, OR = 2.2, 95% CI = 1.0-5.1), but not among graphic
      designers (OR = 1.2, 95% CI = 0.4-3.5). There were no significant differences
      regarding PF OA between the two occupational groups. CONCLUSION: Results
      corroborate the existence of a causal relationship between occupational kneeling
      and radiographic TF OA and suggest a dose-response association with trade
      seniority. An association between kneeling and PF OA was however doubtful.
      Apparent discrepancies between findings in different age groups are most likely
      reflecting selection bias.

PMID- 19594939
TI  - TNF-alpha-induced up-regulation of pro-inflammatory cytokines is reduced by
      phosphatidylcholine in intestinal epithelial cells.
AB  - BACKGROUND: Phosphatidylcholine (PC) is a major lipid of the gastrointestinal
      mucus layer. We recently showed that mucus from patients suffering from
      ulcerative colitis has low levels of PC. Clinical studies reveal that the
      therapeutic addition of PC to the colonic mucus using slow release preparations
      is beneficial. The positive role of PC in this disease is still unclear; however,
      we have recently shown that PC has an intrinsic anti-inflammatory property. It
      could be demonstrated that the exogenous application of PC inhibits membrane
      dependent actin assembly and TNF-alpha-induced nuclear NF-kappaB activation. We
      investigate here in more detail the hypothesis that the exogenous application of
      PC has anti-inflammatory properties. METHODS: PC species with different fatty
      acid side chains were applied to differentiated and non-differentiated Caco-2
      cells treated with TNF-alpha to induce a pro-inflammatory response. We analysed
      TNF-alpha-induced NF-kappaB-activation via the transient expression of a NF
      kappaB-luciferase reporter system. Pro-inflammatory gene transcription was
      detected with the help of a quantitative real time (RT)-PCR analysis. We assessed
      the binding of TNF-alpha to its receptor by FACS and analysed lipid rafts by
      isolating detergent resistant membranes (DRMs). RESULTS: The exogenous addition
      of all PC species tested significantly inhibited TNF-alpha-induced pro
      inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF
      alpha and MMP-1 were significantly reduced after PC pre-treatment for at least
      two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB
      inhibitor SN 50 and was not due to a reduced binding of TNF-alpha to its receptor
      or a decreased surface expression of TNF-alpha receptors. PC was also effective
      when applied to the apical side of polarised Caco-2 cultures if cells were
      stimulated from the basolateral side. PC treatment changed the compartmentation
      of the TNF-alpha-receptors 1 and 2 to DRMs. CONCLUSION: PC induces a prolonged
      inhibition of TNF-alpha-induced pro-inflammatory signalling. This inhibition may
      be caused by a shift of the TNF-alpha receptors at the surface to lipid rafts.
      Our results may offer a potential molecular explanation for the positive role of
      PC seen in clinical studies for the treatment of ulcerative colitis.

PMID- 19594941
TI  - Identification of light-independent inhibition of human immunodeficiency virus-1
      infection through bioguided fractionation of Hypericum perforatum.
AB  - BACKGROUND: Light-dependent activities against enveloped viruses in St. John's
      Wort (Hypericum perforatum) extracts have been extensively studied. In contrast,
      light-independent antiviral activity from this species has not been investigated.
      RESULTS: Here, we identify the light-independent inhibition of human
      immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform
      extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident
      in initial chloroform extracts, but bioassay-guided fractionation produced
      fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of
      these two biological activities has not been reported for constituents
      responsible for the light-dependent antiviral activities. Antiviral activity was
      associated with more polar subfractions. GC/MS analysis of the two most active
      subfractions identified 3-hydroxy lauric acid as predominant in one fraction and
      3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric
      acid inhibited HIV infectivity without cytotoxicity, suggesting that this
      modified fatty acid is likely responsible for observed antiviral activity present
      in that fraction. As production of 3-hydroxy fatty acids by plants remains
      controversial, H. perforatum seedlings were grown sterilely and evaluated for
      presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy
      fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty
      acids were detected in our chloroform extracts or field-grown material.
      CONCLUSION: Through bioguided fractionation, we have identified that 3-hydroxy
      lauric acid found in field grown Hypericum perforatum has anti-HIV activity. This
      novel anti-HIV activity can be potentially developed into inexpensive therapies,
      expanding the current arsenal of anti-retroviral agents.

PMID- 19594942
TI  - Organizational readiness to change assessment (ORCA): development of an
      instrument based on the Promoting Action on Research in Health Services (PARIHS)
      framework.
AB  - BACKGROUND: The Promoting Action on Research Implementation in Health Services,
      or PARIHS, framework is a theoretical framework widely promoted as a guide to
      implement evidence-based clinical practices. However, it has as yet no pool of
      validated measurement instruments that operationalize the constructs defined in
      the framework. The present article introduces an Organizational Readiness to
      Change Assessment instrument (ORCA), organized according to the core elements and
      sub-elements of the PARIHS framework, and reports on initial validation. METHODS:
      We conducted scale reliability and factor analyses on cross-sectional, secondary
      data from three quality improvement projects (n = 80) conducted in the Veterans
      Health Administration. In each project, identical 77-item ORCA instruments were
      administered to one or more staff from each facility involved in quality
      improvement projects. Items were organized into 19 subscales and three primary
      scales corresponding to the core elements of the PARIHS framework: (1) Strength
      and extent of evidence for the clinical practice changes represented by the QI
      program, assessed with four subscales, (2) Quality of the organizational context
      for the QI program, assessed with six subscales, and (3) Capacity for internal
      facilitation of the QI program, assessed with nine subscales. RESULTS: Cronbach's
      alpha for scale reliability were 0.74, 0.85 and 0.95 for the evidence, context
      and facilitation scales, respectively. The evidence scale and its three
      constituent subscales failed to meet the conventional threshold of 0.80 for
      reliability, and three individual items were eliminated from evidence subscales
      following reliability testing. In exploratory factor analysis, three factors were
      retained. Seven of the nine facilitation subscales loaded onto the first factor;
      five of the six context subscales loaded onto the second factor; and the three
      evidence subscales loaded on the third factor. Two subscales failed to load
      significantly on any factor. One measured resources in general (from the context
      scale), and one clinical champion role (from the facilitation scale). CONCLUSION:
      We find general support for the reliability and factor structure of the ORCA.
      However, there was poor reliability among measures of evidence, and factor
      analysis results for measures of general resources and clinical champion role did
      not conform to the PARIHS framework. Additional validation is needed, including
      criterion validation.

PMID- 19594944
TI  - Association of a single nucleotide polymorphism in akirin 2 gene with marbling in
      Japanese Black beef cattle.
AB  - BACKGROUND: Marbling defined by the amount and distribution of intramuscular fat,
      so-called Shimofuri, is an economically important trait of beef cattle in Japan.
      The c17-25 expressed sequence tag (EST) has been previously shown to possess
      expression difference in musculus longissimus muscle between low-marbled and high
      marbled steer groups, and to be located within genomic region of a quantitative
      trait locus for marbling. Thus, the akirin 2 (AKIRIN2) gene containing the c17-25
      EST sequence was considered as a positional functional candidate for the gene
      responsible for marbling. In this study, we explored single nucleotide
      polymorphism (SNP) in the AKIRIN2 and analyzed association of the SNP with
      marbling. FINDINGS: A SNP in the 3' untranslated region of the AKIRIN2, referred
      to as c.*188G>A, was the only difference detected between high- and low-marbled
      steer groups. The SNP was associated with marbling in 3 experiments using 100
      sires (P = 0.041), 753 paternal half-sib progeny steers from 4 sires heterozygous
      for the c.*188G>A (P = 0.005), and 730 paternal half-sib progeny steers from 3
      sires homozygous for the A allele at the c.*188G>A (P = 0.047), in Japanese Black
      beef cattle. The effect of genotypes of the SNP on subcutaneous fat thickness was
      not statistically significant (P > 0.05). CONCLUSION: These findings suggest that
      the AKIRIN2 SNP polymorphism is associated with marbling and may be useful for
      effective marker-assisted selection to increase the levels of marbling in
      Japanese Black beef cattle.

PMID- 19594943
TI  - Neuropathic and nociceptive pain in head and neck cancer patients receiving
      radiation therapy.
AB  - BACKGROUND: Pain is common in head and neck cancer (HNC) patients and may be
      attributed to the malignancy and/or cancer treatment. Pain mechanisms and patient
      report of pain in HNC are expected to include both nociceptive and neuropathic
      components. The purpose of this study was to assess the trajectory of orofacial
      and other pain during and following treatment, using patient reports of
      neuropathic pain and nociceptive pain and pain impact. METHODS: 124 consecutive
      HNC patients receiving radiation therapy (RT) (95 men, 29 women; mean age: 54.7
      +/- 12.3 years) participated in a patient-reported outcome (PRO) assessment.
      Patients completed the McGill Pain Questionnaire three times during therapy and 3
      months following study entry. RESULTS: The majority of patients related their
      pain to the tumor and/or cancer treatment. Whereas 59% reported their pain to be
      less severe than they expected, 29% were not satisfied with their level of pain
      despite pain management during cancer therapy. Worst pain was 3.0 +/- 1.3 on a 0-
      to 5-point verbal descriptor scale. Pain intensity was present at entry, highest
      at 2-week follow-up, declining towards the end of treatment and persisting at 3
      month follow-up. The most common neuropathic pain descriptors chosen were aching
      (20%) and burning (27%); nociceptive words chosen were dull (22%), sore (32%),
      tender (35%), and throbbing (23%), and affective/evaluative descriptors were
      tiring (25%) and annoying (41%). 57% of patients reported continuous pain, and
      combined continuous and intermittent pain was reported by 79% of patients.
      DISCUSSION: This study provides evidence that patients with HNC experience
      nociceptive and neuropathic pain during RT despite ongoing pain management. The
      affective and evaluative descriptors chosen for head and neck pain indicate
      considerable impact on quality of life even with low to moderate levels of pain
      intensity. These findings suggest that clinicians should consider contemporary
      management for both nociceptive and neuropathic pain in head and neck cancer
      patients.

PMID- 19594945
TI  - Changes in spatiotemporal gait variables over time during a test of functional
      capacity after stroke.
AB  - BACKGROUND: Gait dysfunction and fatigue are common post-stroke, though it is
      unclear how extended walking activity, as would be performed during activities of
      daily living, may change over time. The purpose of this study was to examine if
      spatial and temporal gait variables deteriorate during an extended bout of
      walking in a test of functional capacity after stroke. METHODS: 24 community
      dwelling, independently ambulating individuals greater than 3 months after stroke
      performed the Six-Minute Walk Test (6MWT). Participants walked over a pressure
      sensitive mat on each pass of the 30 m course which recorded spatial and temporal
      parameters of gait. Mean gait speed and temporal symmetry ratio during each two
      minute interval of the 6MWT were examined. Additional post hoc analyses examined
      the incidence of rests during the 6MWT and changes in gait speed and symmetry.
      RESULTS: On average, participants demonstrated a 3.4 +/- 6.5 cm/s decrease in
      speed over time (p= 0.02). Participants who rested were also characterized by
      increased asymmetry in the final two minutes (p= 0.05). 30% of participants
      rested at some point during the test, and if a rest was taken, duration increased
      in the final two minutes (p= 0.001). Examination of factors which may have been
      associated with resting indicated that resters had poorer balance (p= 0.006) than
      non-resting participants. CONCLUSION: This study supports previous findings
      establishing that walking performance after stroke declines over relatively short
      bouts of functionally-relevant ambulation. Such changes may be associated with
      both cardiorespiratory and muscular fatigue mechanisms that influence
      performance. The findings also indicate that rest duration should be routinely
      quantified during the 6MWT after stroke, and consequently, further research is
      necessary to determine how to interpret 6MWT scores when resting occurs.

PMID- 19594946
TI  - Flow cytometry analysis of glucocorticoid receptor expression and binding in
      steroid-sensitive and steroid-resistant patients with systemic lupus
      erythematosus.
AB  - INTRODUCTION: Glucocorticoid (GC) therapy is the main treatment for systemic
      lupus erythematosus (SLE). However, some patients are resistant to these agents.
      Abnormalities of glucocorticoid receptor (GR) seem to be related to steroid
      resistance. This study evaluated GRs in T lymphocytes and monocytes of SLE
      patients by flow cytometry (FCM) using a monoclonal antibody (mAb) and FITC-Dex
      probes. METHODS: Thirty-five patients with SLE before treatment and 27 age- and
      sex-matched normal controls were studied. Disease activity scores were determined
      before and after treatment and used to divide the patients into steroid-resistant
      (SR) and steroid-sensitive (SS) groups. GRs in T lymphocytes (CD3+) and monocytes
      (CD14+) were examined by FCM with GR-mAb and FITC-Dex probes before treatment.
      Peripheral blood mononuclear cells (PBMCs) were isolated for in vitro GCs
      sensitivity assays. The validity of FCM analysis of intracellular staining for GR
      with GR-mAb and FITC-Dex probes was evaluated through comparison with western
      blot and radioligand binding assay (RLBA) in U937 and K562 cells in vitro. One
      way ANOVA, student's t test, linear regression and spearman correlation were
      performed. RESULTS: A significant decrease in GR binding and the expression in
      K562 and U937 cells with 10-6 M dexamethasone (Dex) was found compared with those
      without Dex. In addition, a positive correlation was found between FCM and RLBA
      as well as FCM and Western blot. The expression and binding of both CD3/GR and
      CD14/GR in SR patients with SLE, detected by FCM, were all lower than those in SS
      patients with SLE, whereas there was no significant difference in SS patients and
      controls. In vitro corticosteroid sensitivity assay indicated that PHA-stimulated
      tumour necrosis factor-alpha (TNF-alpha), IL-12 and interferon-gamma (IFN-gamma)
      secretion was significantly inhibited by 10-6 M Dexamethasone in all controls and
      SS patients, compared with that in SR group, which confirms patient
      classification as SR and SS by disease activity index (SLEDAI) score.
      CONCLUSIONS: Abnormalities of expression and binding of the GR may be involved in
      tissue resistance to steroids in SLE patients. Determination of GR expression and
      binding by FCM may be useful in predicting the response to steroid treatment of
      SLE patients.

PMID- 19594947
TI  - PCR-based methods for the detection of L1014 kdr mutation in Anopheles
      culicifacies sensu lato.
AB  - BACKGROUND: Anopheles culicifacies s.l., a major malaria vector in India, has
      developed widespread resistance to DDT and is becoming resistant to pyrethroids
      the only insecticide class recommended for the impregnation of bed nets. Knock
      down resistance due to a point mutation in the voltage gated sodium channel at
      L1014 residue (kdr) is a common mechanism of resistance to DDT and pyrethroids.
      The selection of this resistance may pose a serious threat to the success of the
      pyrethroid-impregnated bed net programme. This study reports the presence of kdr
      mutation (L1014F) in a field population of An. culicifacies s.l. and three new
      PCR-based methods for kdr genotyping. METHODS: The IIS4-IIS5 linker to IIS6
      segments of the para type voltage gated sodium channel gene of DDT and pyrethroid
      resistant An. culicifacies s.l. population from the Surat district of India was
      sequenced. This revealed the presence of an A-to-T substitution at position 1014
      leading to a leucine-phenylalanine mutation (L1014F) in a few individuals. Three
      molecular methods viz. Allele Specific PCR (AS-PCR), an Amplification Refractory
      Mutation System (ARMS) and Primer Introduced Restriction Analysis-PCR (PIRA-PCR)
      were developed and tested for kdr genotyping. The specificity of the three assays
      was validated following DNA sequencing of the samples genotyped. RESULTS: The
      genotyping of this An. culicifacies s.l. population by the three PCR based assays
      provided consistent result and were in agreement with DNA sequencing result. A
      low frequency of the kdr allele mostly in heterozygous condition was observed in
      the resistant population. Frequencies of the different genotypes were in Hardy
      Weinberg equilibrium. CONCLUSION: The Leu-Phe mutation, which generates the kdr
      phenotype in many insects, was detected in a pyrethroid and DDT resistant An.
      culicifacies s.l. population. Three PCR-based methods were developed for kdr
      genotyping. All the three assays were specific. The ARMS method was refractory to
      non-specific amplification in non-stringent amplification conditions. The PIRA
      PCR assay is able to detect both the codons for the phenylalanine mutation at kdr
      locus, i.e., TTT and TTC, in a single assay, although the latter codon was not
      found in the population genotyped.

PMID- 19594948
TI  - Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit
      lipopolysaccharide-induced inflammation in vitro and in vivo.
AB  - This study aimed to investigate if food components that exert anti-inflammatory
      effects may be used for inflammatory disorders by examining alfalfa sprout ethyl
      acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with
      acute inflammation after intra-peritoneal (ip) injection of 15 mg/kg BW
      lipopolysaccharide (LPS) were determined. The results showed that the life span
      of LPS-induced inflammatory mice were negatively correlated with serum levels of
      TNF-alpha, IL-6, and IL-1beta at 9 hr after LPS-injection, which indicated that
      suppressing these cytokines in the late phase of inflammation may be beneficial
      for survival. The in vitro experiment then showed that ASEA significantly reduced
      IL-6 and IL-1beta production and the NF-kappaB trans-activation activity of
      mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory
      effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in
      50 microl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate,
      an anti-inflammatory agent) groups were tube-fed with 50 microl sunflower oil/day
      only. After one week of tube-feeding, the PDTC group was injected with 50 mg/kg
      BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS.
      The results showed that the ASEA and PDTC groups had significantly lower serum
      TNF-alpha, IL-6, and IL-1beta levels at 9 hr after LPS challenge, and
      significantly higher survival rates than the control group. This study suggests
      that ASEA supplementation can suppress the production of pro-inflammatory
      cytokines and alleviate acute inflammatory hazards.

PMID- 19594949
TI  - Serum and follicular fluid organochlorine concentrations among women undergoing
      assisted reproduction technologies.
AB  - BACKGROUND: Exposure to persistent organic pollutants, including polychlorinated
      biphenyls (PCBs) and organochlorine pesticides, is widespread among the general
      population. There is evidence of adverse effects on reproduction and early
      pregnancy in relation to organochlorine exposure but human studies remain
      limited. The increased use of assisted reproductive technologies (ART) presents
      unique opportunities for the assessment of environmental influences on early
      pregnancy outcomes not otherwise observable in humans, but studies need to be
      designed to maximize the efficiency of the exposure data collected while
      minimizing exposure measurement error. METHODS: The present study was conducted
      to assess the correlation between concentrations of organochlorines in serum and
      follicular fluid samples collected from a subset of women undergoing ART in a
      large study that took place between 1994 and 2003, as well as the temporal
      reliability of serum organochlorine concentrations among women undergoing
      multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1
      trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE,
      hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in
      72 follicular fluid samples and 265 serum samples collected from 110 women.
      RESULTS: Organochlorine concentrations in paired serum and follicular fluid
      samples were correlated, with Pearson and Spearman coefficients ranging from 0.60
      to 0.92. Serum organochlorine concentrations were two- to three-fold greater than
      in follicular fluid, and a significant inverse trend was observed in the
      distribution of follicular fluid:serum ratios with increasing molecular weight of
      the compound (p-value for trend < 0.0001). Serum organochlorine concentrations
      were highly reliable over the course of several months, with intraclass
      correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence
      for a declining trend in organochlorine concentrations between samples collected
      between years 1994-1998 and those collected in 1999-2003. CONCLUSION: Our results
      support the use of a single serum sample to adequately represent a more
      biologically relevant dose (concentrations in follicular fluid), as well as
      exposure levels over time, in epidemiological studies of ART outcomes in relation
      to organochlorine exposure.

PMID- 19594950
TI  - Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents
      in non-small cell lung cancer cells.
AB  - BACKGROUND: Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to
      preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D
      as a single agent has been demonstrated in vitro and in vivo against various
      cancers, including colon, pancreatic, ovarian and breast cancers. Its human
      safety and potential efficacy are currently being investigated in early clinical
      trials. In this study, we investigated the in vitro combination effects of ReoT3D
      and chemotherapeutic agents against human non-small cell lung cancer (NSCLC).
      RESULTS: ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell
      lines examined, with the 50% effective dose, defined as the initial virus dose to
      achieve 50% cell killing after 48 hours of infection, ranging from 1.46 +/- 0.12
      approximately 2.68 +/- 0.25 (mean +/- SD) log10 pfu/cell. Chou-Talalay analysis
      of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine
      demonstrated strong synergistic effects on cell killing, but only in cell lines
      that were sensitive to these compounds. In contrast, the combination of ReoT3D
      and paclitaxel was invariably synergistic in all cell lines tested, regardless of
      their levels of sensitivity to either agent. Treatment of NSCLC cell lines with
      the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose)
      polymerase cleavage and caspase activity compared to single therapy, indicating
      enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated
      with the ReoT3D-paclitaxel combination showed increased proportions of mitotic
      and apoptotic cells, and a more pronounced level of caspase-3 activation was
      demonstrated in mitotically arrested cells. CONCLUSION: These data suggest that
      the oncolytic activity of ReoT3D can be potentiated by taxanes and other
      chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively
      achieves synergy through accelerated apoptosis triggered by prolonged mitotic
      arrest.

PMID- 19594952
TI  - Finding exclusively deleted or amplified genomic areas in lung adenocarcinomas
      using a novel chromosomal pattern analysis.
AB  - BACKGROUND: Genomic copy number alteration (CNA) that are recurrent across
      multiple samples often harbor critical genes that can drive either the initiation
      or the progression of cancer disease. Up to now, most researchers investigating
      recurrent CNAs consider separately the marginal frequencies for copy gain or loss
      and select the areas of interest based on arbitrary cut-off thresholds of these
      frequencies. In practice, these analyses ignore the interdependencies between the
      propensity of being deleted or amplified for a clone. In this context, a joint
      analysis of the copy number changes across tumor samples may bring new insights
      about patterns of recurrent CNAs. METHODS: We propose to identify patterns of
      recurrent CNAs across tumor samples from high-resolution comparative genomic
      hybridization microarrays. Clustering is achieved by modeling the copy number
      state (loss, no-change, gain) as a multinomial distribution with probabilities
      parameterized through a latent class model leading to nine patterns of recurrent
      CNAs. This model gives us a powerful tool to identify clones with contrasting
      propensity of being deleted or amplified across tumor samples. We applied this
      model to a homogeneous series of 65 lung adenocarcinomas. RESULTS: Our latent
      class model analysis identified interesting patterns of chromosomal aberrations.
      Our results showed that about thirty percent of the genomic clones were
      classified either as "exclusively" deleted or amplified recurrent CNAs and could
      be considered as non random chromosomal events. Most of the known oncogenes or
      tumor suppressor genes associated with lung adenocarcinoma were located within
      these areas. We also describe genomic areas of potential interest and show that
      an increase of the frequency of amplification in these particular areas is
      significantly associated with poorer survival. CONCLUSION: Analyzing jointly
      deletions and amplifications through our latent class model analysis allows
      highlighting specific genomic areas with exclusively amplified or deleted
      recurrent CNAs which are good candidate for harboring oncogenes or tumor
      suppressor genes.

PMID- 19594951
TI  - PR3-ANCA in Wegener's granulomatosis prime human mononuclear cells for enhanced
      activation via TLRs and NOD1/2.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) is autoantibodies
      characteristic of vasculitis diseases. A connection between ANCA and Wegener's
      granulomatosis was well established. The interaction of both ANCA phenotypes (PR3
      ANCA and MPO-ANCA) with leukocytes provoked cell activation, which might be
      involved in the pathogenesis of ANCA-related Wegener's granulomatosis. METHODS:
      In this study, we examined whether PR3-ANCA sera and purified immunoglobulins
      from patients with Wegener's granulomatosis prime human monocytic cells for
      enhanced responses to microbial components in terms of production of
      proinflammatory cytokines. RESULTS: Flow cytometry demonstrated that stimulation
      with antibodies to proteinase 3 enhanced the expression of TLR2, 3, 4, 7, and 9,
      NOD1, and NOD2 in human mononuclear cells. The sera and purified immunoglobulins
      significantly primed human mononuclear cells to secrete interleukin-8 in response
      to microbial components via TLRs and NODs. Priming effects were also observed for
      the production of interleukin-6, monocyte chemoattractant protein-1, and tumor
      necrosis factor-alpha. On the other hand, PR3-ANCA-negative sera from patients
      with polyarteritis nodosa which possibly related to MPO-ANCA and aortitis
      syndrome as well as control sera from a healthy volunteer did not have any
      priming effects on PBMCs. CONCLUSION: In conclusion, PR3-ANCA prime human
      mononuclear cells to produce cytokines upon stimulation with various microbial
      components by up-regulating the TLR and NOD signaling pathway, and these
      mechanisms may partially participate in the inflammatory process in Wegener's
      granulomatosis.

PMID- 19594953
TI  - Preparation and biological properties of a novel composite scaffold of nano
      hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering.
AB  - In this study, we report the physico-chemical and biological properties of a
      novel biodegradable composite scaffold made of nano-hydroxyapatite and natural
      derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC,
      which was prepared by freeze-drying method. The physico-chemical properties of n
      HA/CS/CMC scaffold were tested by infrared absorption spectra (IR), transmission
      electron microscope(TEM), scanning electron microscope(SEM), universal material
      testing machine and phosphate buffer solution (PBS) soaking experiment. Besides,
      the biological properties were evaluated by MG63 cells and Mesenchymal stem cells
      (MSCs) culture experiment in vitro and a short period implantation study in vivo.
      The results show that the composite scaffold is mainly formed through the ionic
      crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated
      into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the
      scaffold with good physico-chemical properties such as highly interconnected
      porous structure, high compressive strength and good structural stability and
      degradation. More important, the results of cells attached, proliferated on the
      scaffold indicate that the scaffold is non-toxic and has good cell
      biocompatibility, and the results of implantation experiment in vivo further
      confirm that the scaffold has good tissue biocompatibility. All the above results
      suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great
      potential to be used as bone tissue engineering material.

PMID- 19594954
TI  - Emergency wounds treated with cyanoacrylate and long-term results in pediatrics:
      a series of cases; what are the advantages and boards?
AB  - BACKGROUND: Ethyl-2-cyanoacrylate (ECA) is a tissue adhesive material applied to
      close superficial wounds. The aim of this study was to explore the benefits of
      cyanoacrylates in the emergency department in children with current application
      with regard to cost-effectiveness, satisfaction and long follow up. FINDINGS:
      Patients were treated after assignment of the consent with an explanation by the
      relatives in a tertiary emergency department (ED), 2007.The evaluation was based
      on different superficial wound repairs due to blunt trauma within a 2-hour time
      period (<6 hours), and small wounds (</=3 cm). These wounds were cleansed with
      serum sale and then dried with gauze. Wound repairs were observed for six months
      in order to observe the tissue changes. The patient's age, sex, indication,
      application time, pain score, cost, additional tending (if needed),
      complications, and cosmetic satisfaction were recorded.A total of 9 patients were
      evaluated and followed for 6 months. Except for one, all children were treated
      without any serious complications. ECA was cost-effective, time-saving, and
      provided successful repair satisfaction by a blinded plastic surgeon and
      patient/parents. CONCLUSION: This report displayed the pediatric effective use of
      cyanoacrylates, even in non- traditional repairs in the emergency departments.

PMID- 19594955
TI  - The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide
      induces DNA damage in EMT-6 mammary carcinoma cells.
AB  - BACKGROUND: DCQ (2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide), a
      synthetic quinoxaline 1,4-dioxide, enhances the cytotoxic effect of ionizing
      radiation (IR) in vivo and in vitro. We sought to clarify whether increased
      radiation-induced DNA damage, decreased rate of damage repair, and the generation
      of reactive oxygen species (ROS) contribute to DCQ enhancement of IR. METHODS:
      Murine mammary adenocarcinoma EMT-6 cells were treated with DCQ for 4 h before
      exposure to 10 Gy IR. Treated cells were monitored for modulations in cell cycle,
      induction of DNA damage, and generation of ROS. RESULTS: Combined DCQ and IR
      treatments (DCQ+IR) induced rapid cell-cycle arrests in EMT-6 cells, particularly
      in S and G2/M phases. Alkaline comet assays revealed high levels of DNA damage in
      cells after exposure to DCQ+IR, consistent with damage-induced arrest. Unlike IR
      only and DCQ-only treated cells, the damage induced by combined DCQ+IR was
      repaired at a slower rate. Combined treatment, compared to separate DCQ and IR
      treatments, activated DNA-protein kinase and induced more p-ATM, supporting a
      role for double strand breaks (DSBs), which are more toxic and difficult to
      repair than single strand breaks (SSBs). Contributing factors to DCQ
      radiosensitization appear to be the induction of ROS and DSBs. CONCLUSION:
      Collectively, our findings indicate that radiosensitization by DCQ is mediated by
      DNA damage and decreased repair and that ROS are at least partially responsible.

PMID- 19594956
TI  - Proliferation of Ty3/gypsy-like retrotransposons in hybrid sunflower taxa
      inferred from phylogenetic data.
AB  - BACKGROUND: Long terminal repeat (LTR) retrotransposons are a class of mobile
      genetic element capable of autonomous transposition via an RNA intermediate.
      Their large size and proliferative ability make them important contributors to
      genome size evolution, especially in plants, where they can reach exceptionally
      high copy numbers and contribute substantially to variation in genome size even
      among closely related taxa. Using a phylogenetic approach, we characterize
      dynamics of proliferation events of Ty3/gypsy-like LTR retrotransposons that led
      to massive genomic expansion in three Helianthus (sunflower) species of ancient
      hybrid origin. The three hybrid species are independently derived from the same
      two parental species, offering a unique opportunity to explore patterns of
      retrotransposon proliferation in light of reticulate evolutionary events in this
      species group. RESULTS: We demonstrate that Ty3/gypsy-like retrotransposons exist
      as multiple well supported sublineages in both the parental and hybrid derivative
      species and that the same element sublineage served as the source lineage of
      proliferation in each hybrid species' genome. This inference is based on patterns
      of species-specific element numerical abundance within different phylogenetic
      sublineages as well as through signals of proliferation events present in the
      distributions of element divergence values. Employing methods to date paralogous
      sequences within a genome, proliferation events in the hybrid species' genomes
      are estimated to have occurred approximately 0.5 to 1 million years ago.
      CONCLUSION: Proliferation of the same retrotransposon major sublineage in each
      hybrid species indicates that similar dynamics of element derepression and
      amplification likely occurred in each hybrid taxon during their formation.
      Temporal estimates of these proliferation events suggest an earlier origin for
      these hybrid species than previously supposed.

PMID- 19594958
TI  - The assessment of dietary adequacy based on nutrient intake data is a complex
      issue. Foreword.

PMID- 19594959
TI  - A review of the use of information and communication technologies for dietary
      assessment.
AB  - Presently used dietary-assessment methods often present difficulties for
      researchers and respondents, and misreporting errors are common. Methods using
      information and communication technologies (ICT) may improve quality and
      accuracy. The present paper presents a systematic literature review describing
      studies applying ICT to dietary assessment. Eligible papers published between
      January 1995 and February 2008 were classified into four assessment categories:
      computerised assessment; personal digital assistants (PDA); digital photography;
      smart cards. Computerised assessments comprise frequency questionnaires, 24 h
      recalls (24HR) and diet history assessments. Self-administered computerised
      assessments, which can include audio support, may reduce literacy problems, be
      translated and are useful for younger age groups, but less so for those
      unfamiliar with computers. Self-administered 24HR utilising computers yielded
      comparable results as standard methods, but needed supervision if used in
      children. Computer-assisted interviewer-administered recall results were similar
      to conventional recalls, and reduced inter-interviewer variability. PDA showed
      some advantages but did not reduce underreporting. Mobile phone meal photos did
      not improve PDA accuracy. Digital photography for assessing individual food
      intake in dining facilities was accurate for adults and children, although
      validity was slightly higher with direct visual observation. Smart cards in
      dining facilities were useful for measuring food choice but not total dietary
      intake. In conclusion, computerised assessments and PDA are promising, and could
      improve dietary assessment quality in some vulnerable groups and decrease
      researcher workload. Both still need comprehensive evaluation for micronutrient
      intake assessment. Further work is necessary for improving ICT tools in
      established and new methods and for their rigorous evaluation.

PMID- 19594957
TI  - Search for a 'Tree of Life' in the thicket of the phylogenetic forest.
AB  - BACKGROUND: Comparative genomics has revealed extensive horizontal gene transfer
      among prokaryotes, a development that is often considered to undermine the 'tree
      of life' concept. However, the possibility remains that a statistical central
      trend still exists in the phylogenetic 'forest of life'. RESULTS: A comprehensive
      comparative analysis of a 'forest' of 6,901 phylogenetic trees for prokaryotic
      genes revealed a consistent phylogenetic signal, particularly among 102 nearly
      universal trees, despite high levels of topological inconsistency, probably due
      to horizontal gene transfer. Horizontal transfers seemed to be distributed
      randomly and did not obscure the central trend. The nearly universal trees were
      topologically similar to numerous other trees. Thus, the nearly universal trees
      might reflect a significant central tendency, although they cannot represent the
      forest completely. However, topological consistency was seen mostly at shallow
      tree depths and abruptly dropped at the level of the radiation of archaeal and
      bacterial phyla, suggesting that early phases of evolution could be non-tree-like
      (Biological Big Bang). Simulations of evolution under compressed cladogenesis or
      Biological Big Bang yielded a better fit to the observed dependence between tree
      inconsistency and phylogenetic depth for the compressed cladogenesis model.
      CONCLUSIONS: Horizontal gene transfer is pervasive among prokaryotes: very few
      gene trees are fully consistent, making the original tree of life concept
      obsolete. A central trend that most probably represents vertical inheritance is
      discernible throughout the evolution of archaea and bacteria, although compressed
      cladogenesis complicates unambiguous resolution of the relationships between the
      major archaeal and bacterial clades.

PMID- 19594960
TI  - Validity of dietary patterns to assess nutrient intake adequacy.
AB  - The purpose of the present study was to conduct a systematic review of the
      literature on the value of the methods used to assess dietary patterns for
      measuring nutrient intake adequacy in the population. Systematic review on Pubmed
      database up to April 2008. The search included specific key words and MeSH terms.
      No language limit was set. Only studies that compared food patterns with nutrient
      intake adequacy or nutrient biomarkers were included in the analysis. The search
      resulted in 1504 articles. The inclusion and exclusion criteria limited the
      selection to thirty articles. Nineteen studies evaluated the usefulness of the
      dietary patterns, either a priori defined (thirteen studies), or defined by
      factor analysis (four studies) or by cluster analysis (two studies), but only
      nine of them tested their validity (four a priori defined and four a posteriori
      defined). Diet indices showed moderate to good validity results for measuring the
      adequacy of intakes for alpha-carotene, beta-carotene, vitamin C, vitamin B6, Ca,
      folic acid, Fe and Mg. The factor analysis approach showed moderate to good
      validity correlations with the adequacy of intake of alpha-carotene, beta
      carotene, lutein, lycopene, vitamin C, vitamin B6 and folic acid. Vitamin B12 and
      vitamin E are the micronutrients with less probability of being adequately
      assessed with dietary patterns a priori or a posteriori defined. Diet indices are
      tools with fair to moderate validity to assess micronutrient intake adequacy.

PMID- 19594961
TI  - Dietary patterns and nutritional adequacy in a Mediterranean country.
AB  - Dietary patterns have been related to health outcomes and morbi-mortality.
      Mediterranean diet indexes are correlated with adequate nutrient intake. The
      objective of the present study was to analyse the adequacy of nutrient intake of
      a posteriori defined Mediterranean (MDP) and Western (WDP) diet patterns in the
      Seguimiento Universidad de Navarra (SUN) cohort. A sample of 17 197 subjects
      participated in the study. Participants completed a 136-item validated semi
      quantitative FFQ. Principal component analysis was used to define dietary
      patterns. Individuals were classified according to quintiles of adherence based
      on dietary pattern scores. Non-dietary variables, such as smoking and physical
      activity habits, were also taken into account. The probability approach was used
      to assess nutrient intake adequacy of certain vitamins (vitamins B12, B6, B3, B2,
      B1, A, C, D and E) and minerals (Na, Zn, iodine, Se, folic acid, P, Mg, K, Fe and
      Ca). Logistic regression analysis was used to assess the adequacy of nutrient
      intake according to adherence to dietary patterns. WDP and MDP were defined. A
      higher quintile of adherence to an MDP was associated to a lower prevalence of
      inadequacy for the intake of Zn, iodine, vitamin E, Mg, Fe, vitamin B1, vitamin
      A, Se, vitamin C and folic acid. The adjusted OR for not reaching at least six
      (or at least ten) nutrient recommendations were 0.09 (95 % CI: 0.07, 0.11) (and
      0.02 (95 % CI: 0.00, 0.16)) for the upper quintile of MDP and 4.4 (95 % CI: 3.6,
      5.5) and 2.5 (95 % CI: 1.1, 5.4) for the WDP. The MDP was associated to a better
      profile of nutrient intake.

PMID- 19594962
TI  - How is the adequacy of micronutrient intake assessed across Europe? A systematic
      literature review.
AB  - EURopean micronutrient RECommendations Aligned is a network of excellence funded
      by the European commission, and established to address the problem of differences
      between countries in micronutrient recommendations as well as to understand how
      nutritional information including requirements and adequacy of intake is
      processed among different population groups. The aims of the present paper were
      to review the methods used for the adequacy assessment of the intake of six
      micronutrients of public health concern (vitamin A, folate, vitamin B12, Fe, Zn
      and iodine) in non-European and European nutrition surveys carried out on the
      apparently healthy population and to compare in particular the adequacy across
      surveys for folate intake. A systematic literature review was conducted to
      identify nutrition surveys that assessed micronutrient intake adequacy. The
      search yielded 9049 records, out of which 337 were eligible for the selected
      micronutrients. The majority (83.9 %) of the European surveys compared the
      adequacy of the nutrient intake against the Recommended Dietary Allowances (RDA);
      only a few surveys (8.0 %) used the estimated average requirement cut-point
      method, while none of them used the probability approach. The comparison of
      folate inadequacy across eight countries revealed that about 25 % of the adult
      female population had inadequate intakes when judged against the different
      recommendations used by the respective investigators, but nearly 75 % had
      inadequate intakes when compared against the estimated average requirement cut
      point value of 320 microg/d. The present review showed that different methods
      were applied across Europe to estimate the adequacy of micronutrient intake,
      which led to different prevalence estimates of micronutrient inadequacy.

PMID- 19594963
TI  - How to find information on national food and nutrient consumption surveys across
      Europe: systematic literature review and questionnaires to selected country
      experts are both good strategies.
AB  - The present research was conducted within the framework of the EURopean
      micronutrient RECommendations Aligned project. In order to identify the best
      practice in assessing nutrient intakes, a search strategy for collecting data
      from national food consumption surveys/studies in Europe was developed.
      Systematic literature searches were carried out on twenty-eight European and the
      four European Free Trade Association countries. A questionnaire was also sent to
      two to five experts in each country. Systematic reviews using PubMed yielded 12
      703 abstracts that were reduced to 200 studies using inclusion and exclusion
      criteria. Similarly, a search of ministry web sites yielded 3033 hits, and
      subsequently reduced to nine surveys. Belgium, France, Germany, Ireland, Sweden,
      Spain and the United Kingdom were the countries with most data and Slovenia and
      Liechtenstein were those with the least. Seventy-eight expert questionnaires were
      obtained from all countries except for Liechtenstein, Luxembourg and Slovakia.
      Detailed results and references are given. A systematic search and questionnaires
      are equally good at identifying national surveys across countries. Literature
      searching provides globally accessible and objective information albeit limited,
      whereas the questionnaire provides information that, depending upon responders,
      can be more complete. A combination of both strategies is recommended.

PMID- 19594964
TI  - How does the quality of surveys for nutrient intake adequacy assessment compare
      across Europe? A scoring system to rate the quality of data in such surveys.
AB  - Research was conducted within the EURopean micronutrient RECommendations Aligned
      (EURRECA) Network of Excellence, to find the best practice in assessing nutrient
      intakes. Objectives include: to search for and use data on individual nutrient
      intake adequacy (NIA) assessment collected in twenty-eight European countries and
      the four European Free Trade Association countries; to design and test innovative
      tools for data quality analysis. The information was obtained using the method
      described by Blanquer et al. in the present issue. The best-practice criteria
      were devised to select the most appropriate survey in each country. Then a survey
      quality scoring system was developed in consultation with experts and tested on
      these surveys. Weights were allocated according to a variable priority order
      agreed by consultation. The thirty-two countries yielded twenty-four national
      surveys (eight countries excluded). Data collection techniques: eleven
      countries/surveys used personal interviews only; six used combinations of
      techniques. Dietary assessment methods: two used repeated 24 h recalls only;
      eleven used combinations. NIA assessment methods: two used probabilistic approach
      and sd/Z-scores only; eleven used comparison with estimated average
      requirements/RDA only. Countries were ranked according to the survey quality
      scoring, but careful interpretation is needed because of incomplete data from
      some surveys; bearing this in mind, the information quality is high in 37.5 %
      countries, medium in 50.0 % and low in 12.5 %. Although there is room for
      improvement and caution should be taken when drawing conclusions and
      recommendations from these results, the lessons learned and tools developed at
      this first attempt form the basis for future work within the EURRECA framework
      for aligning European micronutrient recommendations.

PMID- 19594965
TI  - Overview of methods used to evaluate the adequacy of nutrient intakes for
      individuals and populations.
AB  - The objective of the present paper is to review the methods of measuring
      micronutrient intake adequacy for individuals and for populations in order to
      ascertain best practice. A systematic review was conducted to locate studies on
      the methodological aspects of measuring nutrient adequacy. The results showed
      that for individuals, qualitative methods (to find probability of adequacy) and
      quantitative methods (to find confidence of adequacy) have been proposed for
      micronutrients where there is enough data to set an average nutrient requirement
      (ANR). If micronutrients do not have ANR, an adequate intake (AI) is often
      defined and can be used to assess adequacy, provided the distribution of daily
      intake over a number of days is known. The probability of an individual's intake
      being excessive can also be compared with the upper level of safe intake and the
      confidence of this estimate determined in a similar way. At the population level,
      adequacy can be judged from the ANR using the probability approach or its short
      cut - the estimated average requirement cut-point method. If the micronutrient
      does not have an ANR, adequacy cannot be determined from the average intake and
      must be expressed differently. The upper level of safe intake can be used for
      populations in a similar way to that of individuals. All of the methodological
      studies reviewed were from the American continent and all used the methodology
      described in the Institute of Medicine publications. The present methodology
      should now be adapted for use in Europe.

PMID- 19594967
TI  - Misreporting of energy and micronutrient intake estimated by food records and 24
      hour recalls, control and adjustment methods in practice.
AB  - In order to assess nutritional adequacy, valid estimates of nutrient intake are
      required. One of the main errors in dietary assessment is misreporting. The
      objective was to review the extent, nature and determinants of misreporting in
      dietary assessment, how this affects reported intakes of micronutrients and how
      this is identified and measured, and to identify the best ways of dealing with
      misreporting when interpreting results. A systematic literature search was
      conducted for studies of misreporting of dietary intake in adults by 24 hour
      recalls or by estimated or weighed food records, published up to March 2008.
      Thirty-seven relevant studies were identified. Possible causes of misreporting
      were identified. Methods most used to identify misreporting were the Goldberg cut
      off (46 % studies) and the doubly labelled water technique (24 % studies). The
      magnitude of misreporting of energy intake was similar in all three dietary
      assessment methods. The percentage of under-reporters was about 30 % and energy
      intake was underestimated by approximately 15 %. Seven papers presented usable
      data for micronutrient intake. Absolute intakes of Fe, Ca and vitamin C (the
      three micronutrients addressed in all papers) were on average 30 % lower in low
      energy reporters (LER) than that in non-LER and, although results were not
      consistent, there was a tendency for micronutrient density to be higher in LER.
      Excluding underreporters or using energy adjustment methods for micronutrient
      intakes is discussed. Residual method of energy adjustment seems to be a good
      tool for practice to decrease an influence of misreporting when interpreting
      results of studies based on food records and 24 hour recalls.

PMID- 19594966
TI  - Effects of dietary assessment methods on assessing risk of nutrient intake
      adequacy at the population level: from theory to practice.
AB  - The present study evaluated how applying different dietary methods affects risk
      assessment of inadequate intakes at the population level. A pooled analysis was
      conducted using data from two Spanish regional representative surveys both
      applying similar methodology with a total sample of 2615 individuals aged 12-80.
      Diet was assessed in the entire sample applying data from one 24 h recall (24HR),
      a mean of two non-consecutive 24HR, both crude and adjusted for intraindividual
      variability, and a FFQ. Intakes of vitamins A, C, E, thiamin, riboflavin, niacin,
      vitamin B6, vitamin B12, Fe, Mg, P and Zn were compared to the average nutrient
      requirement (ANR or estimated average requirement) in the entire sample and also
      excluding under-reporters applying the ANR cut-point method (and the probability
      approach for Fe). Higher percentages of intakes below the ANR were seen for 1
      24HR and the mean of 2-24HR, except for nutrients with the highest rates of
      inadequacy (vitamins A, E, folate and Mg). For these micronutrients, higher
      percentages of inadequacy were obtained by adjusted 24HR data and the lowest with
      FFQ. For the remaining nutrients, adjusted data gave the lowest inadequacy
      percentages. The best concordance was seen between 2-24HR and 1-24HR as well as
      for adjusted 24HR, with the least observed between FFQ and the other methods.
      Exclusion of under-reporters considerably reduced inadequacy in both daily
      methods and FFQ. Crude daily data gave higher estimates of inadequate intakes
      than adjusted data or FFQ. Reproducibility of daily methods was also reasonably
      good. Results may differ depending on the micronutrient thus impeding reaching
      conclusions/recommendations common for all micronutrients.

PMID- 19594968
TI  - How dietary intake methodology is adapted for use in European immigrant
      population groups - a review.
AB  - Immigrants comprise a noteworthy segment of the European population whose numbers
      are increasing. Research on the dietary habits of immigrants is critical for
      correctly providing diet counselling and implementing effective interventions.
      The aim of the present study was to identify the presently used methods and
      adaptations required for measuring dietary intake in European immigrant groups. A
      comprehensive review strategy included a structured MEDLINE search, related
      references and key expert consultations. The review targeted adults from non
      European union (European union-15 countries) ethnic groups having the largest
      populations in Europe. As studies evaluating nutrient intake were scarce, papers
      evaluating intake at the level of foods were included. Forty-six papers were
      selected. Although Eastern Europe, Turkey, Africa (North, Sub-Saharan and Afro
      Caribbean), Asia and Latin America represented the most numerous immigrant
      groups, papers on dietary intake were not available for all populations.
      Interview-administered FFQ and repeated 24 hour recalls were the most frequently
      applied instruments. Inclusion of ethnic foods and quantification of specific
      portion sizes of traditional foods and dishes in assessment tools as well as food
      composition databases were commonly identified problems. For FFQ, food list
      elaboration required particular consideration to reflect key ethnic foods and
      relative contribution to nutrient intake. Extra efforts were observed to overcome
      cultural barriers to study participation. Evaluating dietary intake of immigrant
      populations requires special attention to various methodological aspects
      (sampling, recruiting, instruments used, method of administration, food
      composition database, acculturation, etc.) so as to adequately address the range
      of socio-cultural factors inherent in these nutritionally at risk target groups.

PMID- 19594969
TI  - Dietary assessment methods used for low-income populations in food consumption
      surveys: a literature review.
AB  - In order to assess nutritional adequacy, reliable estimates of nutrient intake
      are required. Specifically, the EURopean micronutrient RECommendations Aligned
      (EURRECA) Network of Excellence needs clear guidelines on methods suitable for
      assessing micronutrient intakes among vulnerable population groups. The objective
      of this project was to collect, evaluate data and review the suitability of
      methods used to assess dietary intake of low-income groups across Europe. A
      comprehensive literature review methodology was employed, which involved
      structured search MEDLINE, from 1990 to 2008, on (nutrient intake methods) and
      (validity terms) and (human studies) and finally (low-income terms). In addition,
      manual searches were conducted for published books and national studies. Seven
      studies satisfied the selection criteria for inclusion in the review in which
      four dietary intake methods had been described and validated. Three other studies
      found in the grey literature used similar methods. Only one study tested a
      variety of methods to assess reliability and the method preferred by those having
      low incomes. Preferred methods were 24 h recalls and a FFQ which, compared with
      the weighed inventory, also yielded higher estimates of energy and nutrient
      intakes. Many of the methods used in low-income populations have not been
      subjected to evaluation and consequently may not demonstrate sensitivity and/or
      specificity when used in this population. Based on one study only, four multiple
      pass 24 h recalls are recommended as the most appropriate method for the
      evaluation of nutritional adequacy in low-income households.

PMID- 19594970
TI  - Physician workload and the Canadian Emergency Department Triage and Acuity Scale:
      the Predictors of Workload in the Emergency Room (POWER) Study.
AB  - INTRODUCTION: The Canadian Emergency Department Triage and Acuity Scale (CTAS) is
      a 5-level triage tool used to determine the priority by which patients should be
      treated in Canadian emergency departments (EDs). To determine emergency physician
      (EP) workload and staffing needs, many hospitals in Ontario use a case-mix
      formula based solely on patient volume at each triage level. The purpose of our
      study was to describe the distribution of EP time by activity during a shift in
      order to estimate the amount of time required by an EP to assess and treat
      patients in each triage category and to determine the variability in the
      distribution of CTAS scoring between hospital sites. METHODS: Research assistants
      directly observed EPs for 592 shifts and electronically recorded their activities
      on a moment-by-moment basis. The duration of all activities associated with a
      given patient were summed to derive a directly observed estimate of the amount of
      EP time required to treat the patient. RESULTS: We observed treatment times for
      11 716 patients in 11 hospital-based EDs. The mean time for physicians to treat
      patients was 73.6 minutes (95% confidence interval [CI] 63.6-83.7) for CTAS level
      1, 38.9 minutes (95% CI 36.0-41.8) for CTAS-2, 26.3 minutes (95% CI 25.4-27.2)
      for CTAS-3, 15.0 minutes (95% CI 14.6-15.4) for CTAS-4 and 10.9 minutes (95% CI
      10.1-11.6) for CTAS-5. Physician time related to patient care activities
      accounted for 84.2% of physicians' ED shifts. CONCLUSION: In our study, EPs had
      very limited downtime. There was significant variability in the distribution of
      CTAS scores between sites and also marked variation in EP time related to each
      triage category. This brings into question the appropriateness of using CTAS
      alone to determine physician staffing levels in EDs.

PMID- 19594971
TI  - An overview of injuries to adolescents and young adults related to substance use:
      data from Canadian emergency departments.
AB  - OBJECTIVE: Alcohol is a significant risk factor for injury, and is one of the
      leading causes of death, disability and premature mortality among young
      Canadians. This paper provides an overview of alcohol-related injury among
      adolescents and young adults presenting to Canadian emergency departments (EDs).
      METHODS: We reviewed records from the Canadian Hospitals Injury Reporting and
      Prevention Program database during the 4-year period between 2000 and 2003. We
      included individuals younger than 25 years who presented to EDs in 11 pediatric
      and general hospitals with injuries for which alcohol, either alone or in
      conjunction with drugs, was recorded as a contributing factor. We examined key
      socio-demographic and injury-related factors associated with alcohol and drug
      related injuries, including intent and disposition. RESULTS: Alcohol was
      identified as a factor in 2389 injuries during this 4-year period; 408 (17%) of
      these cases also involved drug use. Approximately 55% of these patients were male
      and the majority was between 15 and 19 years of age. Unintentional injuries were
      the most common presentation, self-harm injuries were more common among female
      patients and violence-related injuries were more common among male patients. Most
      patients received treatment for their injuries. However, as age increased,
      outcome differences were observed between sexes. CONCLUSION: Alcohol-related
      injuries are increasing among Canadian youth. These findings highlight the
      importance of obtaining thorough drug and alcohol histories and measurement, when
      appropriate, for adolescents and young adults presenting to EDs with injuries.

PMID- 19594972
TI  - Chemical, biological, radiological and nuclear preparedness training for
      emergency medical services provider.
AB  - OBJECTIVE: We assessed the self-reported theoretical and practical preparedness
      training of Canadian emergency medical services (EMS) providers in chemical,
      biological, radiological and nuclear (CBRN) events. METHODS: We designed an
      online survey to address the theoretical and practical CBRN training level of
      prehospital providers. Emergency medical services staff in British Columbia and
      Ontario were invited to participate. RESULTS: Of the 1028 respondents, 75% were
      male, and the largest demographic groups were front-line personnel with more than
      15 years of experience. Only 63% of respondents indicated they had received
      either theoretical or practical training to work in a contaminated environment,
      leaving 37% who indicated they had received neither type of training. Of those
      that had received any training, 61% indicated they had received "hands-on" or
      practical training and 82% indicated they had received some training in
      identification of a possibly contaminated scene. Only 42% had received training
      for symptoms of nerve agents, 37% had received training for symptoms of blister
      agents and 46% had received training for symptoms of asphyxiants. Thirty-two
      percent had received training for the treatment of patients exposed to nerve
      agents, and 30% had received training for the treatment of patients exposed to
      blister agents. Only 31% of all respondents had received training for detecting
      radiation. CONCLUSION: CBRN events involve unique hazards and require specific
      education and training for EMS providers. A large proportion of Canadian EMS
      providers report not having received the training to identify and work in
      contaminated environments.

PMID- 19594973
TI  - Effectiveness of a novel training program for emergency medicine residents in
      ultrasound-guided insertion of central venous catheters.
AB  - OBJECTIVE: Insertion of central venous catheters (CVCs) is an essential
      competency for emergency physicians. Ultrasound-guided (USG) insertion of CVCs
      has been shown to be safer than the traditional landmark technique. There is no
      clear consensus on effective methods for training physicians in USG insertion of
      CVCs. We developed and evaluated a novel educational training program in the USG
      technique for insertion of CVCs. METHODS: Sixteen emergency medicine residents
      volunteered for a pre- and postprogram evaluation study, which was approved by
      our research ethics board. After their previous experience was determined, each
      participant was videotaped inserting a USG CVC in the right internal jugular vein
      on models. Participants then reviewed a Web-based instructional module and had a
      practical session. Participants were again videotaped inserting a USG CVC. The
      primary outcome was the change in score before and after the training program,
      using an expert-validated performance evaluation tool used to review the
      videotaped performances in a blinded fashion. Participants also completed a
      questionnaire to measure their satisfaction with the training program and any
      change in their perceived competence. RESULTS: Participants ranged from residency
      year 1 to 5. Thirteen of 16 (81%) had never attempted USG insertion of a CVC.
      Participants reported that the models were realistic. Performance scores (12/19
      to 13.2/19) and global ratings assessments (3.5/7 to 5.5/7) improved
      significantly (p < 0.01; the effect size, Cohen d = 1.12 before and 1.28 after)
      after the instruction. There was good interrater reliability between evaluators
      of the videotaped performances regarding performance scores (r = 0.68) and global
      rating scores (r = 0.75). All participants felt their confidence and technical
      skills were improved (p < 0.01) and all felt satisfied with the training program.
      CONCLUSION: This brief innovative multimethod training program was effective in
      enhancing emergency medicine resident competence in USG insertion of CVCs.

PMID- 19594974
TI  - International Federation for Emergency Medicine model curriculum for medical
      student education in emergency medicine.
AB  - There is a critical and growing need for emergency physicians and emergency
      medicine resources worldwide. To meet this need, physicians must be trained to
      deliver time-sensitive interventions and life-saving emergency care. Currently,
      there is no internationally recognized standard curriculum that defines the basic
      minimum standards for emergency medicine education. To address this deficiency,
      the International Federation for Emergency Medicine convened a committee of
      international physicians, health professionals and other experts in emergency
      medicine and international emergency medicine development, to outline a
      curriculum for foundation training of medical students in emergency medicine.
      This curriculum document represents the consensus of recommendations by this
      committee. The curriculum is designed with a focus on the basic minimum emergency
      medicine educational content that any medical school should be delivering to its
      students during undergraduate training. It is designed not to be prescriptive,
      but to assist educators and emergency medicine leadership in advancing physician
      education in basic emergency medicine content. The content would be relevant not
      just for communities with mature emergency medicine systems, but also for
      developing nations or for nations seeking to expand emergency medicine within
      current educational structures. We anticipate that there will be wide variability
      in how this curriculum is implemented and taught, reflecting the existing
      educational milieu, the resources available and the goals of the institutions'
      educational leadership.

PMID- 19594975
TI  - Diagnostic accuracy and clinical utility of emergency department targeted
      ultrasonography in the evaluation of first-trimester pelvic pain and bleeding: a
      systematic review.
AB  - OBJECTIVE: Emergency department targeted ultrasonography (EDTU) offers the
      possibility of rapid exclusion of ectopic pregnancy in patients with first
      trimester pelvic pain or bleeding. We sought to systematically review the
      evidence describing the diagnostic accuracy and clinical utility of EDTU in the
      first trimester of pregnancy, and to generate a pooled estimate of the
      sensitivity and specificity of EDTU for the detection of intrauterine pregnancy
      (IUP). METHODS: The literature search, abstract review and study selection were
      performed using predefined criteria. We abstracted the sensitivity and
      specificity of EDTU for IUP from included studies, and evaluated and summarized
      the evidence assessing the effect of EDTU use on time to diagnosis, time to
      treatment of ectopic pregnancy, emergency department (ED) length of stay and
      health care costs. RESULTS: The specificity of EDTU for IUP in most studies
      exceeds 98%. The sensitivity in most studies exceeds 90%. Pooled estimates were
      not calculated because of statistical heterogeneity between studies. Published
      evidence indicates that EDTU use reduces the frequency of missed ectopic
      pregnancies, decreases time to surgery for ectopic pregnancy, shortens the length
      of stay for patients with normal pregnancies and may be more cost-effective than
      diagnostic strategies requiring formal ultrasonography. CONCLUSION: EDTU is
      highly specific for the identification of IUP. Patients who have an IUP
      identified with EDTU may be safely discharged from the ED with outpatient follow
      up. The specificity of EDTU for IUP, along with the potential improvements in
      patient care that EDTU affords, justifies its adoption as routine ED care in
      evaluating first-trimester pain or bleeding.

PMID- 19594976
TI  - Emergency department overcrowding as a threat to patient dignity.

PMID- 19594978
TI  - CJEM and pharmaceutical advertisements: it's time for an end.

PMID- 19594980
TI  - Anterior shoulder reductions revisited.

PMID- 19594981
TI  - Seizure activity demonstrated on electrocardiogram.

PMID- 19594982
TI  - Temporal lobe seizures from a posterior cerebral artery aneurysm presenting as
      memory flashbacks.
AB  - Memory flashbacks are usually attributed to recreational drugs or psychiatric
      conditions. The differential diagnosis for memory flashbacks is diverse and
      challenging; moreover, management is influenced by the working diagnosis. We
      describe the case of a 35-year-old man who presented with memory flashbacks
      secondary to temporal lobe seizures from an unruptured aneurysm of the posterior
      cerebral artery. To our knowledge, a case of this nature has not been previously
      reported. This case demonstrates the need to recognize that, on rare occasions, a
      complaint of memory flashbacks can be the result of an organic etiology. We also
      discuss the challenging presentations of temporal lobe seizures, as they can
      easily be misdiagnosed as a psychiatric condition.

PMID- 19594983
TI  - Gone but not forgotten.

PMID- 19594985
TI  - Transition to practice.

PMID- 19594986
TI  - Decision-making about the use of hormone therapy among perimenopausal women.
AB  - OBJECTIVES: Women reaching menopause must make a controversial decision about
      whether to use hormone therapy (HT). The theory of planned behaviour (TPB) was
      the organizing framework. The objectives were to determine if (1) influence of
      different TPB constructs varied with stage of menopause and HT use, (2) women
      with diabetes were influenced in significantly different ways from women without,
      (3) the overall perceived behavioural control (PBC) and self-efficacy (SE) have
      independent effects on intention, and (4) physician influence was mediated by
      subjective norm (SN). DESIGN: Cross-sectional survey of women from a managed care
      organization. METHODS: Multiple regression analysis was used to analyse 765
      responses (230 from women with diabetes) and separately four main subgroups: (1)
      early menopause stage and never used HT, (2) late menopause stage and never used
      HT, (3) late menopause stage and previously used HT, and (4) late menopause stage
      currently using HT. RESULTS: For the entire sample, the model explains 68% of
      variance in intention, where SE, physicians' influence, self-identification with
      menopause as a natural part of ageing, self-identification as someone who wants
      to delay menopause, HT status, menopause status, and diabetes were added to the
      TPB. For the entire sample, SE added 2% to the explained variance and the
      physician determinant added 7%. CONCLUSIONS: An augmented TPB is useful for
      understanding women's HT use decisions. The theory explains more variance in
      intention before a behaviour is enacted than after, and decision structure
      changes over time. PBC and SE have independent effects on intention.

PMID- 19594987
TI  - Response shift in the assessment of quality of life among people attending
      cardiac rehabilitation.
AB  - OBJECTIVES: To examine whether any response shift in quality of life (QoL)
      assessment over the course of a cardiac rehabilitation (CR) programme could be
      explained by changes in individuals' internal standards (recalibration), values
      (reprioritization), and/or conceptualization of QoL and the extent to which any
      response shift could be explained by health locus of control, optimism, and
      coping strategy. DESIGN: Longitudinal survey design. METHODS: The schedule for
      evaluation of individual QoL-direct weighting (SEIQoL-DW) was administered at the
      beginning and end of a CR programme. At the end of the programme, the SEIQoL-DW
      then-test was also administered to measure response shift. A total of 57
      participants completed these measures and other measures to assess health locus
      of control, optimism, and coping. RESULTS: Response shift effects were observed
      in this population mainly due to recalibration. When response shift was
      incorporated into the analysis of QoL a larger treatment effect was observed.
      Active coping as a mechanism in the response shift model was found to have a
      significant positive correlation with response shift. CONCLUSION: This study
      showed that response shift occurs during CR. The occurrence of response shift in
      QoL ratings over time for this population could have implications for the
      estimation of the effectiveness of the intervention.

PMID- 19594990
TI  - A historic moment--the fellowship of rural and remote medicine.

PMID- 19594989
TI  - Adaptation of Western measures of cognition for assessing 5-year-old semi-urban
      Ugandan children.
AB  - BACKGROUND: The majority of available psychometric tests originates from the
      Western World and was designed to suit the culture, language, and socio-economic
      status of the respective populations. Few tests have been validated in the
      developing world despite the growing interest in examining effects of biological
      and environmental factors on cognitive functioning of children in this setting.
      AIMS: The present study aimed at translating and adapting Western measures of
      working memory, general cognitive ability, attention, executive function, and
      motor ability in order to obtain a cognitive instrument suitable for assessing 5
      year-old semi-urban Ugandan children. This population represents a particular
      assessment challenge as school enrolment is highly variable at this age in this
      setting and many children are unused to a formal educational setting. METHODS:
      Measures of the above domains were selected, translated, and modified to suit the
      local culture, education, and socio-economic background of the target population.
      The measures were piloted and then administered to semi-urban Ugandan children
      aged 4;6-5;6, who included children who had started and not yet started school.
      RESULTS: Analysis of validity and reliability characteristics showed that 8 (at
      least one from each domain) out of the 11 measures were successfully adapted on
      the basis that they showed adequate task comprehension, optimum levels of
      difficulty to demonstrate individual and group differences in abilities,
      sensitivity to effects of age and education, and good internal as well as test
      retest reliability. CONCLUSION: Translation and adaptation are realistic and
      worthwhile strategies for obtaining valid and reliable cognitive measures in a
      resource-limited setting.

PMID- 19594988
TI  - Effects of personality on self-rated health in a 1-year randomized controlled
      trial of chronic illness self-management.
AB  - OBJECTIVE: Personality factors moderate self-efficacy enhancing effects of some
      illness self-management interventions, but their influence on self-rated health
      is unclear. This study examined whether high neuroticism and low
      conscientiousness, extraversion, and agreeableness (the distressed personality
      profile) moderated the effects of the homing in on health (HIOH) illness self
      management intervention on mental and physical health status. DESIGN: Analysis of
      data from 384 subjects completing a randomized controlled trial of HIOH. METHODS:
      Regression analyses examined effects of NEO-five factor inventory scores on SF-36
      mental component summary (MCS-36) and physical component summary (PCS-36) scores
      (baseline; 2, 4, and 6 weeks; 6 months; 1 year), adjusting for age, gender, and
      study group. RESULTS: Baseline MCS-36 scores were worse in those with the
      distressed personality profile relative to others: high neuroticism (13.3 points
      worse, 95% confidence interval (CI)=11.0, 15.7) and low conscientiousness (6.6
      points worse, 95% CI=4.1, 9.2), extraversion (10.1 points worse, 95% CI=7.7,
      12.5) and agreeableness (4.2 points worse, 95% CI=1.6, 6.8). Intervention
      subjects had better MCS-36 scores at 4 and 6 weeks, and benefits were confined to
      participants with low conscientiousness (4 weeks - 3.7 points better, 95% CI=0.2,
      71; 6 weeks - 5.0 points better, 95% CI=1.57, 8.4). There were no intervention or
      personality effects on PCS-36 scores. CONCLUSIONS: Chronically ill self
      management intervention recipients with the distressed personality profile had
      worse self-rated mental health, and conscientiousness moderated the short-term
      effects of the intervention on self-rated mental health. Measuring personality
      may help identify individuals more likely to benefit from self-management
      interventions.

PMID- 19594991
TI  - President's message. "Who do I get next?".

PMID- 19594992
TI  - Teaching children's mental health to family physicians in rural and under
      serviced areas.
AB  - OBJECTIVE: To evaluate a curriculum for teaching family physicians (FPs) in rural
      and underserviced areas about children's mental health, and to evaluate a
      collaborative model of teaching using child psychiatrists and FPs. METHODS: A
      child psychiatrist and a rural FP provided training to rural FPs in attention
      deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs).
      Training consisted of a half-day workshop in 11 communities located in
      southwestern Ontario. Workshops included didactic teaching, observation of
      standardized videos demonstrating interviewing skills, and interactive
      discussion. Participants completed pre- and posttraining questionnaires about
      their confidence in managing these conditions, and completed standardized
      questionnaires on the effectiveness of the workshop and videos. One month after
      the training, participants were randomly assigned to receive individual
      interviews. Three months later 2 questionnaires were mailed to participants for
      evaluation of their confidence after their training and for evaluation of the
      impact on their practice. RESULTS: Fifty-six FPs attended the workshops and, of
      these, 80% completed the study. Family physicians reported improved confidence in
      their abilities to diagnose and treat ADHD and DBDs after the training.
      CONCLUSION: Didactic presentations by child psychiatrists and FPs, followed by
      video examples of interviewing skills, and informal discussions with small
      groups, was found to be an effective curriculum for teaching rural FPs about
      children's mental health.

PMID- 19594993
TI  - Meeting Canadian emergency department triage and acuity scale benchmarks in a
      rural emergency department.
AB  - INTRODUCTION: The Canadian Emergency Department Triage and Acuity Scale (CTAS)
      was implemented in 1999. The CTAS aims to more accurately define patients' needs
      for timely care and provide operating objectives to standardize this care. These
      objectives are not being met across Ontario. The purpose of this study was to
      determine if the CTAS benchmarks were being met at a rural emergency department
      (ED). METHODS: All ED visits to South Huron Hospital from Apr. 1, 2003, to Mar.
      31, 2004, were reviewed. The percentage of visits receiving each CTAS category (I
      V) was calculated. The median and 90th percentile time to physician initial
      assessment (PIA) were quantified by CTAS level. RESULTS: There was a total of 10
      286 ED visits with 113 (1.1%) excluded because of missing triage codes. The
      percentage of visits assigned to CTAS categories I to V was 0.3, 2.4, 16.0, 42.7
      and 38.5, respectively. Time to PIA in minutes was 1, 12, 24, 28 and 27 for CTAS
      I to V, respectively. CONCLUSION: The CTAS guidelines for PIA were met at this
      rural ED.

PMID- 19594995
TI  - Abridged version of the Society of Rural Physicians of Canada's discussion paper
      on rural hospital service closures.

PMID- 19594994
TI  - Issues related to medical students' engagement in integrated rural placements: an
      exploratory factor analysis.
AB  - OBJECTIVE: The purpose of this study was to identify and investigate the factors
      derived from the rural integrated community clerkship (RICC) questionnaire that
      influenced the decision of medical students to pursue a 36-week rural community
      placement option. METHODS: A total of 162 first-year (n = 92) and second-year (n
      = 70) medical students completed the 35-item RICC questionnaire. We used
      qualitative interviews to develop questionnaire items, and we used subsequent
      descriptive statistics and exploratory factor analyses to analyze the data.
      RESULTS: Students with origins in rural communities were not significantly more
      likely to consider a RICC than their urban counterparts. However, students who
      identified family medicine as their discipline of choice were 3 times more likely
      to consider a RICC. Exploratory factor analysis, based on correlation of
      questionnaire items, determined 7 factors (themes) for the questionnaire. The
      questionnaire had strong internal reliability (Cronbach a = 0.94). CONCLUSION:
      Although generally supportive of the rural clerkship option, students are less
      concerned about the clinical experience than they are about the practical
      implications of moving to a rural community. The RICC questionnaire was shown to
      have strong reliability and construct validity in measuring students' perceptions
      of a long-term clerkship placement in a rural community.

PMID- 19594996
TI  - The occasional D & C.

PMID- 19595000
TI  - Country cardiograms case 34: answer.

PMID- 19594998
TI  - Can international medical graduates help solve Canada's shortage of rural
      physicians?

PMID- 19595002
TI  - [Role of surgeon in the multimodality therapy of solid tumors].

PMID- 19595001
TI  - [Diagnosis and treatment of endocrine tumor of pancreas].

PMID- 19595003
TI  - [Diagnosis and surgical treatment for non-functional islet cell tumor: a
      retrospective analysis of 44 cases].
AB  - OBJECTIVE: To evaluate the methods of diagnosis and surgical treatment for
      nonfunctional islet cell tumor (NICT). METHODS: Forty-four patients with non
      functional islet cell tumor treated at the First Affiliated Hospital of Nanjing
      Medical University during January 1968 to June 2008 were analyzed
      retrospectively. There were 9 males and 35 females, aged from 7- to 70-years-old.
      Clinical manifestation: 15 cases (34.1%) of abdominal masses, 17 patients (38.6%)
      with epigastric or back pain, 5 cases of jaundice, 5 cases (11.4%) for upper
      abdominal fullness or vomiting, 10 cases (22.7%) of pancreatic tumor noticed by
      routine health checkups or imaging examinations. Imaging examination: CT scan,
      sonography, ERCP, MRI, upper GI series were performed in 33 (75.0%), 16 (36.4%),
      6 (13.6%), 2 (4.5%), and 10 cases (22.7%) respectively. Operation methods: 39
      patients (88.6%) underwent surgical resection and the other 5 patients did not.
      RESULTS:  COMPLICATIONS: pancreatic fistula in 7 patients (15.9%), intra
      abdominal bleeding in 4 (9.1%), gastrojejunal anastomosis outlet obstruction in 1
      (2.3%), biliary fistula in 2 (4.5%) and incisional infection in 3 (6.8%). Surgery
      related mortality happened in 2 patients (4.5%), both treated before 1999. Twenty
      five patients underwent operation between January 1999 and June 2008 were
      followed up for 6 to 108 months. All survive except one died 75 months after the
      surgery for unknown reason. CONCLUSIONS: No specific clinical manifestation is
      recognized for non-functional islet cell tumor. Spiral CT is an optimal
      diagnostic method, while surgery is the first choice for treatment. Middle
      segmental pancreatectomy has become an alternative surgical protocol for NICT.

PMID- 19595004
TI  - [Diagnosis and treatment of multiple endocrine neoplasia type 1 related
      pancreatic endocrine tumors].
AB  - OBJECTIVE: To summarize the experience on diagnosis and treatment of multiple
      endocrine neoplasia type 1 (MEN-1) related pancreatic endocrine tumors (PET).
      METHODS: From January 2004 to December 2007, there were 10 patients of MEN-1
      related PET were treated in Shanghai Jiaotong University School of Medicine
      Affiliated Ruijin Hospital. There were 2 males and 8 females, aged from 11- to 49
      years-old. They were diagnosed by laboratory tests, imaging examinations and
      genes sequencing. Drug therapy, surgery and follow-up were applied on the
      patients. RESULTS: There were 9 patients having insulinomas including 2 cases of
      multiple insulinomas and 1 case presenting an insulinoma, multiple nonfunctional
      PET and malignant duodenum gastrinoma with liver metastasis. The other patient
      was diagnosed as glucagonoma clinically. Five cases had family history and MEN-1
      gene mutation was detected in 9 patients. Seven patients accepted nine
      operations. Twelve insulinomas, four nonfunctional PET and one duodenum
      gastrinoma were found in the operations. All patients were followed up from 1
      month to 11 years, and 9 patients with good conditions and 1 patient died.
      CONCLUSIONS: Well recognizing PET and MEN-1, early diagnosing MEN-1 related PET,
      appropriately surgical intervention will prove patients' life quality and will
      help for prolonging patients' survival time.

PMID- 19595005
TI  - [Clinical experience in diagnosis and treatment of glucagonoma].
AB  - OBJECTIVE: To study the diagnosis and treatment of glucagonoma. METHODS: A
      retrospective review of glucagonoma cases was committed between June 1993 and
      July 2008 in Peking Union Medical College Hospital. It was measured by sex, age,
      misdiagnosis, clinical symptoms, laboratory data, imaging studies, diagnosis,
      treatment procedures and so on. RESULTS: The tumors of eleven cases were found in
      the tail, and one case was in the head of the pancreas at the same time. Ten had
      solitary lesion, one had multiple lesions. The average diameter of the lesions
      was 3.9 cm. Nine patients had the metastasis out of pancreas and all of them had
      the liver metastasis. One case was a member of multiple endocrine neoplasia type
      1 (MEN-1) syndromes. Eight patients being treated with operation had the detailed
      pathological reports. The glucagon was detected by immunohistochemistry and was
      positive in five patients. Six patients were pathologically malignant. Multimodal
      treatments included tumor resection, chemoembolization, treated with somatostatin
      analogues and (or) radionuclides and so on were applied to all patients.
      CONCLUSIONS: Glucagonoma is a rare pancreatic endocrine tumor. Radical tumor
      surgery is used as the first choice. Multimodal approach may improve the
      prognosis.

PMID- 19595006
TI  - [The application of intraoperative ultrasonography in the diagnosis and therapy
      of insulinoma].
AB  - OBJECTIVE: To analyze the value of intraoperative ultrasonography (IOUS) in the
      diagnosis and therapy of insulinoma. METHODS: From January 2000 to December 2007,
      the application of intraoperative ultrasonography used in 44 cases with
      insulinoma who came from department of general surgery, First Affiliated Hospital
      of Zhengzhou University were retrospectively analyzed. There were 19 males and 25
      females in the group. Every case accepted operation and examination of IOUS.
      RESULTS: Tumor was accurately located and its adjacent structure was also clear
      by IOUS in 43 cases, the other one was islet cell hyperplasia, the detection rate
      of tumor was 100%. The complications: one case occurred pancreatic fistula, one
      occurred pancreatitis, and there was no biliary fistula and hemorrhage.
      CONCLUSIONS: Presently, IOUS is one simple and effective method to local
      insulinoma, and it could improve the success rate of operation and reduce
      complications.

PMID- 19595011
TI  - [Prospective study on the role of MRI and B ultrasonography in evaluating the
      tumor response to neoadjuvant chemotherapy in breast cancer].
AB  - OBJECTIVE: To evaluate the role of breast B ultrasonography and magnetic
      resonance imaging in assessing the tumor response to neoadjuvant chemotherapy in
      breast cancer. METHODS: Eighty-five patients with breast cancer diagnosed by core
      needle biopsy received neoadjuvant chemotherapy entered this prospective study.
      Breast B ultrasonography and dynamic enhanced MRI was performed before
      chemotherapy induction, after the second course and the fourth course of
      chemotherapy prior to the surgery. Clinical evaluation was made through the tumor
      reduction measured by B ultrasonography and MRI, based on the response evaluation
      criteria in solid tumors (RECIST). RESULTS: Measured by dynamic enhanced MRI, 56
      patients got partial response (PR), 27 got stable disease (SD) and 2 got
      progressive disease (PD), none complete response (CR). Measured by B
      ultrasonography, 52 patients got PR, 31 got SD, 2 got PD, no CR. Residual tumor
      size after chemotherapy on MRI correlated well with post-operative pathologic
      findings (r = 0.783, P < 0.05), and B ultrasonography correlated moderately with
      microscopic findings (r = 0.576, P < 0.001). CONCLUSION: Dynamic enhanced MRI is
      a reliable method to evaluate tumor response to neoadjuvant chemotherapy in
      breast cancer.

PMID- 19595012
TI  - [A clinical comparison of two strategies for minimal invasive treatment of
      secondary common bile duct stone].
AB  - OBJECTIVE: To compare the clinical efficiency of two strategy in the treatment of
      secondary common bile duct stones: laparoscopic cholecystectomy with transcytotic
      common bile duct exploration (LC + LTCBDE), or laparoscopic cholecystectomy after
      endoscopic sphincterotomy (EST + LC). METHODS: According to the screening
      standard, 88 patients with secondary bile duct stones (43 cases in LC + LTCBDE
      group, 45 cases in EST + LC group) who were treated from June 2005 to November
      2007 were analyzed retrospectively. The achievement ratio, complications, average
      hospital stay and cost between two groups were compared. And all patients were
      followed up. RESULTS: There were no significant differences on achievement ratio
      and complications between two groups (P > 0.05). The LC + LTCBDE group has
      significantly shorter hospital stay and lower cost (P < 0.05). There were no
      recurrence in 1 year. CONCLUSIONS: LTCBDE is a promising strategy which has more
      advantages in the minimal invasive treatment of secondary common bile duct
      stones.

PMID- 19595013
TI  - [Effects of primary deep venous valvular incompetence of lower limb in deep vein
      thrombus after total knee replacement].
AB  - OBJECTIVE: To evaluate the effects of primary deep venous valvular incompetence
      of lower limb (PDVI) to the occurrence of deep vein thrombosis (DVT) after human
      total knee replacement (TKR). METHODS: One hundred and twenty-six patients who
      planed to receive TKR were examined by color doppler flow imaging (CDFI). The
      patients were divided into 2 groups depending on whether they were found
      backstreaming in femoral vein or not. When the refluxing time > 1 s, the patients
      were included in PDVI group; When the refluxing time < or = 1 s, the patients
      were included in without PDVI group. In 7 d after operation all the patients were
      re-examined by CDFI to find if there was DVT. The results were tested by chi2
      statistical analysis. RESULTS: Among the 126 patients, 54 had PDVI, and 72
      without PDVI. Fifty patients had DVT, total incidence rate 39.7% (50/126). In
      PDVI group 33 patients had DVT (61.1%, 33/54); In without PDVI group 17 patients
      had DVT (23.6%, 17/72), which was lower than PDVI group (chi2 = 21.227, P <
      0.05). CONCLUSIONS: PDVI may be a risk for occurrence of DVT after TKR.

PMID- 19595014
TI  - [Primary clinical result of digital template as navigation to supper cervical
      pedicle instrumentation].
AB  - OBJECTIVE: To observe the primary clinical result of digital template as
      navigation to the upper cervical pedicle instrumentation. METHODS: CT scan of
      upper cervical vertebrae was performed. 3-D model of upper cervical vertebrae was
      reconstructed by software Amira 3.1 and was preserved in STL format. Then 3-D
      model was run in software UG Imageware 12.0, the best pedicle channel was
      extracted according to the reverse engineering principle. A virtual navigational
      template was established according to he lamina anatomic trait, and the best
      pedicle channel. The virtual vertebrae and navigational template were
      manufactured using rapid prototyping. The navigational template was sterilized
      and used intra operative to assist with the placement of pedicle screw. The
      Accuracy of screw placement was confirmed with postoperative X-ray and CT
      scanning. RESULTS: The digital navigational template had been established and
      used in the 3 cases, the good trajectory of cervical pedicle had been showed by
      the CT scan of post operation. There were not complications of related pedicle
      screw insertion. CONCLUSIONS: A novel method of upper cervical pedicle location
      using Reverse Engineering and rapid prototyping has been developed; the
      navigational template is found to be highly accuracy and has great expectation.

PMID- 19595015
TI  - [Comparative analysis of several invasive methods in treating postoperative
      sputum retention].
AB  - OBJECTIVE: To compare the indications and therapeutic effects of several invasive
      interventions in treating postoperative sputum retention. METHODS: Bronchoscopy,
      cricothyroidotomy, intubation or tracheotomy was performed in 112 patients with
      postoperative sputum retention from January 2002 to December 2006. There were 95
      male and 17 female patients. The age ranged from 14- to 81-years-old with a mean
      of (65.2 +/- 11.1) years old. Their clinical data were collected to prove the
      improvement of PaO2, SpO2, and pulmonary atelectasis. Sputum clearance results of
      these invasive methods were compared as well. RESULTS: Bronchoscopies were
      effective in 24 out of 60 cases (40.0%), while the rest 36 cases called for
      multiple bronchoscopies or other maneuvers. Tracheal intubations were effective
      in 31.2% (15/48) patients, among whom 11 patients required further
      cricothyroidotomies, and 22 patients required tracheotomies. Intubations and
      bronchoscopies resulted shorter intervention durations and efficacy durations,
      comparing with the other two methods. CONCLUSIONS: Personalized risk analysis
      helps decision making in invasive interventions for postoperative sputum
      clearance. Tracheal intubations and bronchoscopic clearance are helpful in short
      term symptomatic relief and recommended the first choice in cases of
      postoperative sputum retentions.

PMID- 19595016
TI  - [The comparative analysis of video-assisted thoracoscopic versus transsternal
      thymectomy for myasthenia gravis].
AB  - OBJECTIVE: To investigate different characteristics of the video-assisted
      thoracoscopic (VATS) versus transsternal thymectomy for myasthenia gravis (MG).
      METHODS: The clinical data of 106 patients who underwent VATS thymectomy for MG
      between February 2002 and May 2007, and 108 patients who underwent transsternal
      thymectomy between March 1998 and August 2003 were analyzed retrospectively. In
      VATS group, there were 64 male and 42 female patients, and the mean age was 38
      years-old. In the transsternal group, 68 patients were male and 40 were female,
      and the mean age was 36-years-old. Analysis of conditions related to the surgical
      procedure between two groups was made, such as length of surgery, operative
      bleeding, postoperative drainage, hospital stay, hospitalization expenses and
      complications. The mean time of follow-up was 38.5 months (ranging from 10 to 67
      months). All patients were classified according to the MGFA clinical
      classification. RESULTS: Intraoperative bleeding in VATS group was (34 +/- 5) ml,
      significantly less than (150 +/- 23) ml in the transsternal group. Postoperative
      drainage in VATS group was (42 +/- 18) ml, significantly less than (168 +/- 31)
      ml in the transsternal group. Complications and hospital stay in VATS group were
      also significantly lower than those in the transsternal group. There was no
      significantly different in the long-term outcome between two groups. CONCLUSION:
      Although both thoracoscopic and transsternal approaches to thymectomy in patients
      with MG are effective after the long-term follow-up, VATS thymectomy has its
      specific advantages of minimal invasion, less complications, and rapid recovery.

PMID- 19595017
TI  - [Influence of liver regeneration after partial hepatectomy on the development of
      liver metastasis of colon cancer in rats].
AB  - OBJECTIVE: To investigate the stimulated effect of liver regeneration on colon
      cancer cells in remnant liver in rats. METHODS: Rat models with liver metastases
      or retro-peritoneal metastases of colon cancer were established: animals
      underwent 37% or 70% liver resection and were compared with a sham laparotomy
      (15, 25, 15 cases, respectively). Metastases were performed two weeks before
      resection. Rats were killed 3 weeks after the resection. Total body weight, liver
      and tumor weights were recorded. The human colon adenocarcinoma cell line Lovo
      was cultured in the presence of portal serum withdrawn 24 hours and 14 days after
      partial hepatectomy (PH). DNA synthesis was assessed by flow cytometry analysis
      for 5-Bromodeoxyuridine (5-BrdU) incorporation. RESULTS: The tumor growth was
      accelerated in the remnant liver in 70% PH group, but the tumors in 37% PH group
      and retro-peritoneal site were not influenced by PH. Compared with the control
      group, after cultured 72 hours with portal serum withdrawn 24 h after PH, a
      higher 5-BrdU incorporation was found in the Lovo cell lines (P < 0.05), and it
      reached the peak after 120 hours of culture (P < 0.05). No difference was found
      between the groups when cultured with the portal serum withdrawn 14 d after PH (P
      > 0.05). CONCLUSIONS: PH may accelerate the growth of residual microscopic tumor
      in the liver which contributes to local recurrence. It has no systemic effect and
      effects on the cancer cell lines in extrahepatic sites. The excision extension is
      related to the stimulating effects on the cancer cell line, and subtotal
      hepatectomy is presumably a major determinant.

PMID- 19595018
TI  - [Selection of the early stage differentially expressed genes in rat lung tissue
      by cDNA microarray after total hepatic ischemia reperfusion injury].
AB  - OBJECTIVE: To examine the early changes in gene expression levels in lung tissues
      by cDNA microarray using a rat model of total hepatic ischemia reperfusion and to
      analysis function of the changes. METHODS: Twelve adult male SD rats weighting
      220 - 250 g were divided randomly into two groups (6 in each group). The rats
      were sacrificed at end point of the operation and lung tissues were divided into
      several parts for either microarray analysis or RT-PCR of several genes selected
      from microarray data. Common change genes were selected from three chips and the
      final results of microarray analysis were identified by RT-PCR. At last,
      differentially expressed genes were classified according to their biological
      functions by cluster analysis. RESULTS: Analysis of the results showed those 48
      genes up-regulated and 32 genes down-regulated after hepatic ischemia reperfusion
      lung injury. Only parts of them had we known about the function. Genes
      significantly up-regulated were IL-1 alpha, IL-1 beta, SLPI, MMP9, MMP14, MMP15,
      TIMP1, PIK3RL, MAPK, NF-kappaB, JNK and others. Genes significantly down
      regulated were CYP1A1, NQO1, GSTA3, RETNLA and others. Differentially expressed
      genes were mainly classified into inflammatory reaction, transcription factors,
      cell metabolism, signals transduction, ion or receptors, cytoskeleton, etc.
      CONCLUSIONS: cDNA microarray technique provides a new method for detecting
      differentially expressed genes in rat lung tissues. Further study may reveal the
      molecular pathologic mechanism of hepatic ischemia reperfusion lung injury and
      discern new targets for therapeutic interventions.

PMID- 19595019
TI  - [Locally administered lentivirus-mediated siRNA inhibits wear debris-induced
      inflammation].
AB  - OBJECTIVE: To determine the safety and efficacy of local administration of
      lentivirus-mediated small interfering RNA (siRNA) targeting tumor necrosis factor
      alpha (TNF-alpha) in murine air pouch model. METHODS: From May 2007 to April 2008
      a siRNA targeting TNF-alpha and a missense siRNA were designed, and recombine
      lentivirus which coexpressed the green fluorescent protein (GFP) as a marker gene
      was constructed. Air pouches were established and stimulated by Ti-6Al-4V
      particles. Pouches were divided into 3 groups randomly. Lentivirus-mediated siRNA
      targeting TNF-alpha (TNF-alpha group) or lentivirus-mediated missense siRNA (MS
      group), or virus-free saline (control group) were injected into pouches
      respectively. Pouch membrane, peripheral blood, heart, liver, spleen, kidney,
      lung and brain were harvested at 28 d after transfection, and assayed for markers
      of inflammation using histological, molecular, immunological techniques and
      Xenogen in vivo imaging system (IVIS) 50 vivo bioluminescent assay system.
      RESULTS: Xenogen IVIS 50 vivo image revealed strong expression of GFP localized
      in pouch areas and no expression in other parts of mice both in TNF-alpha group
      and MS group at 4 weeks after transfection, while no expression of GFP was found
      in control group. By RT-PCR and ELISA, the mRNA and protein levels of TNF-alpha
      in TNF-alpha group decreased by 81.6% and 82.6% respectively compared to control
      group (P < 0.01), and decreased by 78.9% and 84.0% respectively compared to MS
      group (P < 0.01), whereas TNF-alpha level in peripheral blood, heart, liver,
      spleen, kidney, lung and brain remained invariant (P > 0.05). Less inflammatory
      responses (thinner pouch membrane and decreased cellular infiltration) were
      observed in TNF-alpha group. CONCLUSION: Efficient local delivery of lentivirus
      mediated siRNA targeting TNF-alpha into modified murine air pouch can inhibit
      debris-induced inflammation effectively, with no systemic adverse effects.

PMID- 19595020
TI  - [Human osteoblasts response to different magnitudes of mechanical stimulation in
      vitro].
AB  - OBJECTIVE: To investigate the effect of different magnitudes of tensile strain on
      human osteoblasts differentiation. METHODS: According to the strain amplification
      mechanism at cellular level and a data calculated by finite element analysis, the
      cellular level strain of 0.8%, 1.6%, 2.4% and 3.2% was respectively applied to
      human osteoblasts for 48 h at a frequency of 1 Hz. Alkaline phosphatase activity
      and the expression of osteoblast-related genes were detected by Semi-Quantitative
      RT-PCR and densitometric analysis. RESULTS: Alkaline phosphatase activity
      significantly increased at 0.8% and 1.6%. The level of osteocalcin mRNA increased
      at 2.4% and 3.2%. Cbfa1/Runx2 gene expression only increased at 3.2%. Comparing
      to static control, mRNA level of type I collagen increased at every magnitude.
      The mRNA level decreased at 0.8% and increased at 3.2% when compared to the group
      with 1.6% elongation. CONCLUSIONS: Higher magnitudes of strain enhance expression
      of osteocalcin, type I collagen gene and Cbfa1/Runx2 in human osteoblasts, but
      lost the ability to increase ALP activity which is remained by lower magnitudes
      of strain. Type I collagen gene expression increases in a strain magnitude
      dependent manner.

PMID- 19595029
TI  - [Be a surgeon will versed in both operative management and rational perioperative
      use of antibiotics].

PMID- 19595021
TI  - [Total knee arthroplasty in Charcot arthritis patients].
AB  - OBJECTIVE: To discuss the results of total knee arthroplasty undertaken for
      Charcot arthritis patients. METHODS: Between September 2000 and January 2007, 4
      consecutive patients (2 men and 2 women; 5 TKAs) with Charcot arthritic knees
      were treated. At the time of surgery, the mean age of the patients was 67.3 years
      (64 to 72 years). One had bilateral and 2 had unilateral TKA and one had
      ipsilateral total hip and total knee arthroplasty. The mean knee society score
      before operation was 33.75 points. RESULTS: The mean follow-up was 65 months (19
      to 96 months). The mean knee society score post-operation had improved to 95.25
      points in 5 TKAs with no occurrence of infection and loosening. All 4 patients
      were very satisfactory with the clinical results at the last follow-up.
      CONCLUSIONS: The midterm follow-up data indicated that total knee arthroplasty to
      treat Charcot arthritis could get good clinical results. The postoperative
      results in Charcot arthritis were closed related with the proper prosthesis and
      surgical technique.

PMID- 19595030
TI  - [The treatment of coronary artery surgery: principles and relevant problems].

PMID- 19595031
TI  - [Coronary artery bypass grafting in patients over 70 years old].
AB  - OBJECTIVE: To retrospectively analyze the experiences, indications, technique,
      and results of coronary artery bypass grafting (CABG) in patients over 70 years
      old. METHODS: Ninety-one patients received coronary artery bypass grafting from
      March 2004 to March 2008. Ages ranged from 70 to 83 years old, 22 patients over
      75 years old. Conventional CABG (CCABG) in 72 patients, off-pump CABG (OPCAB) in
      19 patients. Clinical data has no significant differences in two groups. The rate
      of using left internal mammary artery was 96.7%. The number of grafts in CCABG
      and OPCAB group were 2 to 5 (3.5 +/- 0.8) and 1 to 4 (2.9 +/- 0.7) respectively.
      RESULTS: In-hospital death in 2 cases, both were from chronic obstructive
      pulmonary disease and pulmonary infection. Cerebral infarction in 1 case and
      pulmonary infection in 2 cases in CCABG group, but no significant difference
      between two groups, and no difference in intubation, ICU stay, respiratory
      failure, renal function failure. But number of grafts in CCABG was significantly
      more than that in OPCAB (P < 0.01). Postoperative follow-up was 3 to 36 months, 1
      case with recurrent angina in OPCAB. CONCLUSIONS: According to the characteristic
      of coronary artery disease in elderly, fully revascularization and improving
      myocardial blood supply, patients over 70 years old with CABG can obtain the same
      efficacy as younger patients. There were not significant difference between CCABG
      and OPCAB.

PMID- 19595032
TI  - [Minimally invasive robotic coronary bypass on the beating heart using da Vinci S
      system].
AB  - OBJECTIVE: To summarize the experience of minimally invasive robotic coronary
      bypass on beating heart using da Vinci S in China. METHODS: Fifty-six patients
      underwent selected robotic coronary bypass on beating heart from April 2007 to
      December 2008. All the patients had history of angina and the coronary
      arteriography showed severe stenosis in the left anterior descending artery
      (LAD), of which 10 cases had right coronary artery or left circumflex coronary
      (LCX) stenosis. The age was 33 to 74 years old, with a mean of (55.8 +/- 9.4)
      years old. The weight was (71.4 +/- 13.2) kg. All the patients had good lung
      function and had no medical history of pleurisy and thoracic surgery. CT scan of
      double internal thoracic artery (ITA) was routinely checked preoperatively. The
      procedures included: (1) The robotically assisted endoscopic atraumatic coronary
      artery bypass surgery. The approach was via a small left anterior thoracotomy (6
      to 8 cm) after robotic ITA was taken down. The ITA was manually anastomosed to
      the LAD or LCX on beating heart. (2) Totally endoscopic coronary bypass graft on
      beating heart. After ITA harvesting, the endo stabilizer was inserted via the
      fourth port in the xiphoid area under endoscopic vision. The left ITA to the LAD
      grafting was done using U-clips on beating heart in a totally endoscopic manner
      using da Vinci S system through 4 ports. For all patients the ITA flow was
      checked by the Doppler flowmeter after anastomosis was completed. After the
      surgery was completed, the thoracic port was checked carefully to avoid bleeding.
      The operating procedures and a variety of clinical parameters were recorded and
      analyzed. (3) Stent placement after robotic surgery in a hybrid manner. The graft
      patency rate was evaluated by CT or arteriography. RESULTS: All patients
      successfully accepted robotic minimally invasive coronary bypass on the beating
      heart using da Vinci S surgical system without complications. The mean graft flow
      was (23.2 +/- 16.7) ml/min. And there was no surgical conversion and surgical
      death. Fifty-three patients received ITA to LAD grafts and 3 patients received
      double coronary artery bypass grafts as well. Ten cases received stent placement
      in separate session. The CT scan and angiography revealed patent grafts in all
      patients. There were no post-operative complications. All patients were
      discharged from hospital. CONCLUSIONS: As a new advanced approach of
      revascularization, robotic ITA harvesting and coronary anastomoses can be safely
      performed with the da Vinci S system. The procedure is minimally invasive and can
      offer enhanced ability to control precise and stable operative manipulations.

PMID- 19595033
TI  - [The clinical effect and long-term follow-up of minimally invasive direct
      coronary artery bypass grafting via left anterior small thoracotomy].
AB  - OBJECTIVE: To estimate the clinical effect and long-term follow-up of minimally
      invasive direct coronary artery bypass grafting (MIDCAB) via left anterior small
      thoracotomy. METHODS: MIDCAB via left anterior small thoracotomy approach was
      performed in 38 cases of coronary artery disease with single or multi-vessel
      involvement from January 2002 to October 2006. There were 25 males and 13 females
      with a mean age of (63.3 +/- 11.1) years old. The left internal mammary artery
      (LIMA) was harvested under direct vision or with the assistance of thoracoscopy.
      After heparinization the pericardium was directly opened to expose the target
      vessels. The coronary artery bypass grafting was completed on beating heart.
      RESULTS: The procedure were smoothly completed in all the 38 cases. The LIMA was
      anastomosed to the left anterior descending artery (LAD) or the diagonal artery
      in 20 cases, while two bypass grafts were performed in 8 cases (including 3 cases
      of sequential grafting and 5 cases of LIMA-radial artery Y-shaped grafting).
      Hybrid procedure was performed on 10 patients. There were no serious
      postoperative complications and operative deaths found. All the 38 cases except
      one were followed for 26 to 82 (53.2 +/- 28.5) months and no myocardial
      infarction or death occurred. NYHA class were I in 26 cases and II in 12 cases.
      There were 3 recurrence of angina, 2 patients relieved their symptoms with
      medication while 1 patient received stent implantation because of anastomose
      stenosis confirmed by coronary angiography 2 years after surgery. CONCLUSIONS:
      MIDCAB via left anterior small thoracotomy has low rate of mortality and adverse
      cardiac events. The long-term follow-up is good.

PMID- 19595034
TI  - [Increasing cardiopulmonary bypass flow volume improves outcome of patient with
      carotid stenosis undergoing coronary artery bypass grafting].
AB  - OBJECTIVE: To evaluate the effect of increasing cardiopulmonary bypass (CPB) flow
      volume in improving outcome of patients with carotid artery stenosis performed
      coronary artery bypass grafting (CABG) procedure. METHODS: Fifty-one patients
      data collected from January 2006 to March 2008 and divided into two groups (A and
      B) based on the degree of the carotid artery stenosis diagnosed by ultrasound.
      Group A included 15 cases with one or both carotid artery stenosis more than 50%,
      14 male and 1 female, aged (68.5 +/- 7.7) years old, 14 with hypertension, 2 with
      diabetes, 6 with myocardial infarction, 3 with cerebral infarction. Group B
      included 36 cases with stenosis less than 50%, 34 male and 2 female, aged (62.4
      +/- 10.2) years old, 28 with hypertension, 7 with diabetes, 20 with myocardial
      infarction. Increasing CPB flow volume in A group to compare cerebral blood flow
      (CBF) within procedure in both groups. RESULTS: CPB flow volume in group A was
      much higher than it in group B (P = 0.001). Mean arterial blood pressure in group
      A was (67.0 +/- 9.1) mm Hg (1 mm Hg = 0.133 kPa), higher than group B (59.0 +/-
      7.1) mm Hg (P = 0.009). There was no significant difference of CBF within
      procedure and neuropsychologic performance in both group as result. CONCLUSION:
      For the patients presenting with carotid artery stenosis undergoing the procedure
      of CABG with CPB, increasing CPB flow volume could improve significantly diseased
      side cerebral blood flow and might reduce neurological complications.

PMID- 19595035
TI  - [Endoscopic radial artery harvest for coronary artery bypass grafting:
      applications and histologic assessment].
AB  - OBJECTIVE: To observe the influence of endoscopic radial artery harvesting
      techniques on the prevalence of complications after coronary artery bypass
      grafting, and to assess the potential trauma to the radial artery through the
      histological changes. METHODS: From August 2003 to June 2008, 87 patients
      undergoing CABG had radial artery harvested by endoscopic harvesting system.
      About 4 mm proximal and distal radial artery end segment of 10 patients
      undergoing endoscopic and conventional harvesting were examined with light and
      electro-microscope. RESULTS: The endoscopic harvest time was 42 to 98 min, with a
      mean of (57.6 +/- 17.3) min. The harvested conduit length was 15 to 20 cm, with a
      mean of (17.5 +/- 1.6) cm. Objective dorsal thenar numbness remained in 7
      patients, none complained of forearm numbness at 3-month follow-up. The result of
      light and electro-microscope had no differences in the intima, media, or
      adventitia between endoscopically and conventionally obtained radial artery
      segments. CONCLUSION: The use of endoscopic radial artery harvesting in coronary
      artery bypass grafting can be performed safely with infrequent complications.
      This method results in excellent patient satisfaction, particularly regarding the
      cosmetic outcome.

PMID- 19595036
TI  - [The predictive values of EuroSCORE of early mortality in coronary artery bypass
      grafting patients].
AB  - OBJECTIVE: To verify the predictive value of EuroSCORE of early mortality in
      coronary artery bypass grafting (CABG) patients. METHOD: From January 2005 to
      March 2007, 310 consecutive patients were operated with CABG. Detailed data for
      the EuroSCORE risk factor were collected and all patients were scored according
      to the EuroSCORE additive model, retrospectively or prospectively. Expected or
      predicted mortality was calculated for individual patients using the EuroSCORE
      algorithms, arranged sequentially in order of predicted score. The population was
      divided into three clinically relevant risk categories according to the range of
      predicted mortality rate. Expected mortality was compared to observed or actual
      mortality for each risk category. Mortality was defined as death from any cause
      within 30 days of operation or within the same hospital admission. RESULTS:
      Preoperative overall patients: low-risk group was 25.2% (78/310), middle-risk
      group was 48.4% (150/310), high-risk group was 26.4% (82/310). In the EuroSCORE
      model, predicted mortality was 1.4% for low-risk group, 2.7% for middle-risk
      group, 7.4% for high-risk group, and 3.6% for overall patients. Actual mortality
      was 0, 1.3% and 3.7% respectively, overall early mortality was 1.6%. Area under
      the ROC curve was 0.78. CONCLUSION: The EuroSCORE yield good predictive value for
      hospital mortality of patients undergoing CABG, especially in off-pump CABG.

PMID- 19595037
TI  - [The value of hepatic ischemic preconditioning in hepatectomy with a prospective
      randomized controlled study].
AB  - OBJECTIVE: To evaluate the value of ischemic preconditioning in clinical
      hepatectomy. METHODS: A total of 48 unselected patients undergoing liver
      resection were analyzed by randomized controlled trial from December 2004 to June
      2006. Forty-eight unselected patients were randomized into two groups: IP group
      (5 minutes of ischemia followed by 5 minutes of reperfusion) and control group
      (received Pringle's maneuver no and no IP was given). Postoperative days 1, 3 and
      7, the liver function were checked. Perioperative mortality, morbidity and
      hospitalized days were compared. RESULTS: In IP group, ischemic times were 5 - 80
      min, mean 31 min, hospitalized days were 13 - 50 days, mean 20 days. In control
      group, ischemic times were 10 - 60 min, mean 27 min, hospitalized days were 10 -
      33 days, mean 17 days. Forty-seven patients were satisfactory with postoperative
      recovery, except one patient died of chronic liver dysfunction after 3 months
      postoperatively. Postoperative days 1, 3 and 7, the ALT, AST, TBIL, ALB levels in
      two groups were not statistically significant (P > 0.05). CONCLUSIONS: The
      clinical use of IP through 5 minutes of warm ischemia in this technique of
      hepatectomy does not protect the liver from hepatic injury induced by the IRI.

PMID- 19595038
TI  - [Liver transplantation in end-stage liver disease with portal vein thrombosis].
AB  - OBJECTIVE: To summarize the experience in the managements of portal vein
      thrombosis (PVT) and to evaluate the impact of PVT on intraoperative course and
      postoperative outcome in liver transplantation. METHODS: Between May 1995 and
      September 2007, 194 orthotopic liver transplantations were performed, of which 24
      cases presented portal vein thrombosis. There were 12 patients with grade I, 9
      with grade II, 2 with grade III and 1 with grade IV. The management of PVT
      depended mainly on its extent. Ligation of the collateral circulation, especially
      spontaneous or surgical splenorenal shunt, was made as approaches to improve
      portal flow.Heparin or low-molecule-weight heparin as a prophylactic
      anticoagulation therapy was maintained during and after operation if prothrombin
      time is less than eighteen seconds. Follow-up Doppler ultrasonography was used
      daily in the early postoperative period. Risk factors and variables associated
      with the transplant and the post-transplant period were analyzed and compared
      with 170 patients transplanted without PVT. RESULTS: Surgical techniques were
      eversion thromboendovenectomy in 21 patients with PVT grades I and II, extra
      anatomic mesenteric graft in 2 with grade III, and anastomosis to a collateral
      vein in 1 with grade IV. The study demonstrated more RBC transfusions [(15.2 +/-
      11.8) U vs. (8.6 +/- 6.6) U, P = 0.006], longer surgery procedures [(492 +/- 89)
      min vs. (403 +/- 105) min, P = 0.001] and hospital stay [(32.4 +/- 13.5) d vs.
      (22.1 +/- 9.1) d, P = 0.001] in the PVT group. However, there were no differences
      in overall morbidity (58.3% vs. 50.6%, P = 0.478), hospital mortality (8.3%
      vs.6.5%, P = 0.73) and 1-year survival (87.5% vs. 89.4%, P = 0.778). The
      incidence of rethrombosis was higher in the PVT group (8.3% vs.1.2%, P = 0.021).
      Two cases rethrombosis were successfully cured by percutaneous thrombolysis,
      balloon angioplasty, and stent placement. CONCLUSION: Portal thrombosis is
      associated with greater operative complexity and rethrombosis, but has no
      influence on overall morbidity and mortality in liver transplantation.

PMID- 19595039
TI  - [Factors associated with anastomotic leakage after anterior resection in rectal
      cancer].
AB  - OBJECTIVE: To analyze the factors associated with anastomotic leakage after
      anterior resection in rectal cancer with the technique of total mesorectal
      excision (TME). METHODS: From January 2005 and December 2007, 738 consecutive
      patients with rectal cancer underwent anterior resection. The data of those
      patients was collected and reviewed retrospectively. The associations between
      anastomotic leakage and 9 patient-related variables as well as 7 surgical-related
      variables were examined. RESULTS: Low rectal cancer (located 7 cm or less above
      the anal edge), non-specialized surgeon and transanal tube use were the risk
      factors associated with anastomotic leakage on univariate analysis. The
      anastomotic leakage rate of low-rectal cancer was significantly higher than that
      of high-rectal cancer (5.9% vs. 0.9%, P = 0.003). The anastomotic leakage rate of
      the cases operated by colorectal surgeon was significantly lower than that of the
      cases operated by non-specialized surgeon (3.9% vs. 11.3%, P = 0.031). There was
      a tendency for colorectal surgeons to operate on a greater proportion of low
      rectal cancer than non-specialized surgeons (72.1% vs. 52.8%, P = 0.003). The
      leakage rate of transanal tube group was unexpectedly higher than that in
      patients without transanal tube (14.5% vs. 3.6%, P < 0.001). On multivariate
      logistic regression analysis, diabetes mellitus (P = 0.027), distance less than 1
      cm from tumor to distal resection margin (P = 0.009) and defunctioning stoma (P =
      0.031) were also associated with anastomotic leakage rate besides low rectal
      cancer, non-specialized surgeon and transanal tube use. In a further analysis of
      522 patients with low rectal cancer, the leakage rate of defunctioning stoma
      group was significantly lower than that of non-stoma group (2.9% vs. 8.5%, P =
      0.007). By contract, the leakage rate of transanal tube group was still higher
      than that in patients without transanal tube (15.1% vs. 4.9%, P = 0.008) because
      of its poor protective effect as well as the selection bias. CONCLUSIONS: Low
      rectal cancer, non-specialized surgeons and diabetes mellitus are risk factors of
      anastomotic leakage after rectal surgery. A defunctioning stoma was effective in
      preventing leakage after low-rectal cancer surgery.

PMID- 19595040
TI  - [Study on the tumor infiltration in mesorectum of rectal cancer by spiral
      computed tomography and histopathology].
AB  - OBJECTIVE: To evaluate the value of spiral computed tomography in the
      preoperative assessment of the degree of tumor infiltration in mesorectum and
      circumferential resection margin status of rectal cancer compared with large
      tissue slice technique. METHODS: Fifty-seven patients with rectal cancer
      diagnosed by fiber colonoscopy and pathology from March 2007 to December 2007
      underwent preoperative 64-layers spiral CT examination. The degree of tumor
      infiltration in mesorectum and circumferential resection margin status were
      evaluated. Large tissue slice technique was applied in the pathologic study after
      the total mesorectal excision of the rectum to determine the degree of tumor
      infiltration in mesorectum and the circumferential resection margin status. The
      spiral CT findings were compared with pathologic results. The accuracy,
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of the CT results were assessed respectively. RESULTS: The overall
      spiral CT accuracy was 93.0% (53/57) for the degree of tumor infiltration in
      mesorectum, and it was 94.7%, 94.7% and 96.5% for degree I, II, III infiltration,
      respectively. Fifty-three cases (93.0%) were accurately predicated with the
      circumferential resection margin status. The sensitivity, specificity, PPV and
      NPV of spiral CT measurement was 80.0%, 97.6%, 92.3% and 93.2%, respectively, and
      was consistent well with the histopathological diagnosis. CONCLUSIONS: Spiral CT
      provides accurate preoperative assessment for the degree of tumor infiltration in
      mesorectum and circumferential resection margin status of rectal cancer.

PMID- 19595041
TI  - [Transplantation of large anterior latissimus dorsi muscular flap combination
      with musculus rectus abdominis flap].
AB  - OBJECTIVE: To study the value and surgical techniques of transplantation of large
      anterior latissimus dorsi muscular flap combination with musculus rectus
      abdominis flap. METHODS: Three cases (2 male and 1 female) with skin defect and
      bone exposed were reviewed from May 2005 to January 2007. Two patients suffered
      from trauma, and 1 suffered from tumor resection. Flaps size were: 60 cm x 32 cm,
      55 cm x 30 cm and 50 cm x 25 cm, flaps pattern including: 1 free flap with 2 ends
      of vascular, 1 flap with pedicle and free vascular end, 1 flap with 2 ends of
      pedicle. RESULTS: Two flaps survived completely, 1 flap with necrosis edge
      eventually healed after change of dressing. The infection had been effectively
      controlled and ready for function recovered. One case caused by trauma recovered
      with fracture healing, full weight-bearing and restore the original work.
      CONCLUSIONS: Large anterior latissimus dorsi muscular flap combination with
      musculus rectus abdominis flap can be used for repair of large skin defect. For
      the difficulty and technical requirements, surgical indications should be
      strictly controlled.

PMID- 19595042
TI  - [A clinical study on different decompression methods in cervical spondylosis].
AB  - OBJECTIVE: To analyze the different decompression methods to treat cervical
      spondylosis based on imageological evaluation. METHODS: Two hundred and sixty
      three consecutive patients with cervical spondylosis between Nov. 2004 and Oct.
      2007 were involved in this study. Patients were distributed to different
      operation groups based on the preoperative imageological evaluation, including
      anterior or posterior decompression methods. The Anterior method is to use the
      discectomy of one to three segments, autogenous iliac graft or titanium mesh or
      cage fusion and titanium plate fixation, or subtotal vertebrectomy of one to two
      segments autogenous iliac graft or titanium mesh fusion and titanium plate
      fixation, or discectomy plus subtotal vertebrectomy, The posterior expansive
      single open door laminoplasty and other operation types. All the patients were
      divided into different groups by the preoperative imageological evaluation, age,
      sex and course of diseases. Then we collected each group's preoperative and
      postoperative JOA scores and mean improvement rate to evaluate the postoperative
      effect by different decompression methods. RESULTS: Two hundred and thirty five
      patients were followed up with a mean period of 18 months (range, 4 to 36
      months). JOA scores of all patients were improved by different degrees after
      operations. Anterior and posterior decompression methods both can achieve higher
      mean improvement rates. There were no significant differences in mean improvement
      rates between anterior groups, and so did male and female (P > 0.05). The effect
      will decrease as age increases or the course of disease prolongs. Statistical
      significance existed among the different age groups and between course groups (P
      < 0.05). CONCLUSIONS: Anterior and posterior decompression methods both can
      achieve good effect. The key point is to choose the surgical indication
      correctly, decompress thoroughly, and make the fusion reliable and fixation firm.
      In regard to the patients' imageological evaluation, the methods should be
      differentiated. The anterior operation type included discectomy of one to three
      segments, subtotal vertebrectomy of one to two segments and discectomy plus
      subtotal vertebra ectomy.

PMID- 19595043
TI  - [Anterior decompression for the treatment of cervical spondylotic myelopathy
      associated with ossification of posterior longitudinal ligament].
AB  - OBJECTIVE: To study the technique and effect of anterior decompression for the
      treatment of cervical spondylotic myelopathy associated with ossification of
      posterior longitudinal ligament (OPLL). METHOD: Sixty-one patients (42 male and
      19 female, 45 - 74 years with mean age of 57 years old) underwent anterior
      decompression for the treatment of cervical spondylotic myelopathy associated
      with OPLL. Among them, OPLL was definitely diagnosed in 49 patients
      preoperatively, and was found during the operation in the other 12 patients. The
      occupying rate of OPLL ranged 32%-70% with an average of 52%. The preoperative
      JOA scores ranged 4 - 14 points with an average of 9.6 points. In additional to
      conventional decompression, the ossification was removed completely after
      discectomy and corpectomy. RESULTS: Corpectomy was performed in 41 cases,
      discectomy in 6 cases and combination of corpectomy and discectomy in 14 cases.
      The follow-up of all patients ranged from 6 to 36 months (mean 16 months). The
      postoperative JOA scores ranged 8-16 points with an average of 12.8 points. The
      neurological improvement rate ranged from 25.0% to 87.5% with an average of
      65.2%. The transient leakage of cerebrospinal fluid (CSF) occurred in 5 cases,
      and stopped after conservational treatment. No neurological deterioration
      developed. CONCLUSIONS: The difficulty and risk of anterior decompression are
      significantly increased in the patients with cervical spondylotic myelopathy
      associated with OPLL. Remove of ossification after corpectomy and discectomy
      could provide complete decompression and better results.

PMID- 19595044
TI  - [Endovascular interventional treatment for symptomatic stenosis of middle
      cerebral artery].
AB  - OBJECTIVE: To study the feasibility, security and validity of percutaneous
      angioplasty (PTA) or percutaneous angioplasty and stenting (PTAS) for symptomatic
      stenosis of middle cerebral artery. METHODS: The results of treatment and follow
      up of 39 cases with symptomatic stenosis of middle cerebral artery who had either
      recurrent transient ischemic attacks (TIAs) or resistant to medical therapy and
      were performed PTA or PTAS were studied retrospectively. RESULTS: Among the 39
      cases with stenosis of middle cerebral artery (23 in left, 13 in right, 3 in
      bilateral side and 5 cases combining with stenosis of carotid artery) PTA were
      successfully performed in 9 cases and PTAS in 30 (whose post-operative residual
      stenosis were less than 10%). After operation the patients were administrated
      with antiplatelet drugs. The clinic symptom and sign of ischemia were improved
      obviously after operation. During the procedure the contrast could be seen
      outside the vessel in 2 cases, the patients had no obvious symptom of hemorrhage
      and got well rapidly. But in another case her consciousness changed 1 h after
      PTAS and the limbs could not move in right side. Emergency CT scan showed
      cerebral hemorrhage in left basic node area. The patient suffered language
      barrier and incomplete hemiplegy in right side. No complication was occurred in
      the others. During 5 to 60 months follow-up, the symptom of weakness in right arm
      reoccurred but lighter than before in only one case. TCD rechecked in 26 cases
      and demonstrated the blood beam speed was faster than normal in two case. DSA
      rechecked in 14 cases showed restenosis in-stent in the 2 cases and they were
      treated by medicine. CONCLUSIONS: PTA and PTAS is a feasible, safe and effective
      therapeutic method for the patients with symptomatic stenosis of middle cerebral
      artery. Further study in large number of patients is needed for long-term
      outcome.

PMID- 19595046
TI  - [Clone screening and interference efficiency of seed cells with CCL20 gene
      knockdown for tissue-engineered skin].
AB  - OBJECTIVE: To screen stable cell clones of CCL20 gene knockdown and assess their
      interference effects, recombinant lentivirus vectors with CCL20 gene specific
      shRNA were applied to infect human immortal keratinocyte line (HaCaT). METHODS:
      The three pHSER-CCL20-shRNA-GFP vectors (pHCG-1 and pHCG-2 were CCL20 gene
      specific, and pHCG-3 was used as mismatch control) have been previously
      constructed. The virus packaging cell line 293FT was transfected with these
      vectors by using CaCl2 methods to produce lentiviral particles. After the viral
      titers of these three harvested cell supernatants were determined by flow
      cytometry, HaCaT cells were transfected by these viruses and screened under the
      pressure of G418. The CCL20 mRNA from HaCaT cell clones and the CCL20 protein
      levels in the supernatants of HaCaT cell clones were detected by Real-time RT-PCR
      and ELISA, respectively. RESULTS: The titers of three lentiviruses were 7.08 x
      10(5) transduced units (TU)/ml, 1.88 x 10(5) TU /ml and 2.08 x 10(5) TU/ml,
      respectively. Two HaCaT cell clones from each lentiviral vectors were obtained
      after G418 screening for 5 - 8 weeks. Four CCL20 gene specific clones showed
      stable interference effect in both Real-time RT-PCR and ELISA. The mRNA
      expression and protein level of CCL20 gene specific clones were down regulated
      significantly. CONCLUSIONS: The four human immortal keratinocyte clones with long
      term CCL20 gene knockdown have been screened by recombinant lentivirus vectors
      with CCL20 gene specific shRNA. These clones might be served as seed cells for
      novel tissue-engineered skin with lower rejection.

PMID- 19595045
TI  - [Study on the correlation between CD14 gene polymorphism and T cell-mediated
      immunity in severely burned patients].
AB  - OBJECTIVE: To investigate the correlation between CD14 gene polymorphism and T
      cell-mediated immunity in severely burned patients. METHODS: The blood samples of
      77 patients with extensive burn injury (> 30% total body surface area) were
      collected, and CD14-159C/T gene polymorphism was determined by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). T lymphocyte cell
      proliferation and interleukin-2 (IL-2) production were determined, and the ratio
      of CD4(+)/CD8(+) T lymphocyte as well as apoptosis of CD4(+) T lymphocyte was
      examined by flow cytometry. RESULTS: The ability of T lymphocyte proliferation
      was obviously decreased in severely burned patients. Compared with CC homozygote
      patients, proliferative activity of T lymphocyte to mitogen stimulation was
      significantly depressed in TT and TC patients on post burn days 5, 21, and 28 (P
      < 0.05 or P < 0.01). IL-2 production in TT, TC patients was constantly in low
      level after burns, while it was increased from post burn day 14 in CC patients.
      The ratio of CD4(+)/CD8(+) T lymphocytes was markedly decreased in TC, TT
      patients than that in CC patients, especially on post burn days 1, 3, 14, 21, and
      28 (P < 0.05 or P < 0.01). Meanwhile, compared with CC homozygote patients, the
      apoptosis rates of CD3(+)CD4(+) T lymphocytes were much higher in TT patients on
      post burn days 5, 7, and 21 (P < 0.05), and in TC patients on days 7, 14 (P <
      0.05), respectively. However, no obvious differences in parameters of immune
      function of T lymphocytes were found between TT and TC patients (P > 0.05).
      CONCLUSION: CD14-159C/T polymorphism could influence the T cell-mediated immunity
      in extensively burned patients, which might participate in the development of
      septic complications secondary to major burns.

PMID- 19595054
TI  - [Information changes recognition: clinical use of continuous glucose monitoring
      system].

PMID- 19595055
TI  - [Correlation between the amplitude of glucose excursion and plasma 8-iso
      prostaglandin F2alpha level in subjects with different types of glucose
      regulation].
AB  - OBJECTIVE: To investigate the effect of glucose excursion on oxidative stress
      that is expressed by plasma 8-iso prostaglandin F2alpha (8-iso) level. METHODS:
      Continuous glucose monitor system (CGMS) was used to calculate the mean amplitude
      of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation
      (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial
      glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood
      glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and
      mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose
      regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25
      patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma
      8-iso level was determined by EIA. RESULTS: The plasma 8-iso level of the T2DM
      patients was 230 ng/L, significantly higher than that of the subjects with IGR
      (199 ng/L, P < 0.05) and that of the NGR subjects (156 ng/L, P < 0.01). Patients
      with T2DM also had higher levels of glycated hemoglobin (HbA1c), MBG, SDBG, 1 h
      pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P <
      0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the
      IGR subjects were all significantly higher than those of the NGR individuals (P <
      0.05 or 0.01). Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG,
      1 h pre-PG, 3 h PPG, MODD, and HbA1c in all groups. Further analysis showed that
      the relationship between plasma 8-iso level and MAGE remained significant after
      adjustment for the other parameters of glucose excursion in multiple linear
      regression analysis (multiple R(2) = 0.55 for the model including MAGE).
      Standardized regression coefficients were 0.694 (P = 0.000) for MAGE. CONCLUSION:
      Glucose excursion exhibits a stronger triggering effect on oxidative stress than
      chronic sustained hyperglycemia in the subjects with IGR and T2DM.

PMID- 19595056
TI  - [Characteristics of glycometabolism in the first-degree relatives of type 2
      diabetes patients assessed by continuous glucose monitoring system].
AB  - OBJECTIVE: To investigate the characteristics of glycemic stability in the first
      degree relatives of type 2 diabetes mellitus (T2DM) patients by continuous
      glucose monitoring system (CGMS). METHODS: Twenty-two first-degree relatives
      (FDRs) of T2DM patients and 28 age and gender-matched controls underwent CGMS to
      obtain the mean blood glucose (MBG), standard deviation of MBG (SDBG), mean of
      daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). Oral
      glucose tolerance test (OGTT) was conducted. Blood glucose, serum lipids, and
      serum insulin were assayed. The insulin sensitivity and resistance was assessed
      by HOMA-beta, HOMA-IR, DeltaI(30)/DeltaG(30) and modified beta cell function
      index (MBCI). RESULTS: There were no significant differences between the FDR and
      control groups in the levels of plasma glucose in OGTT, MBG, SDBG, and MOOD.
      However, the MAGE level of the FDR group was (2.3 +/- 0.5) mmol/L, significantly
      higher than that of the control group [(2.0 +/- 0.6) mmol/L, P < 0.05]. The MBCI
      level of the FDR group was 17.6 (16.9 - 50.0), significantly lower than that of
      the control group [36.0 (15.7 - 59.6), P < 0.05]. There were no significant
      differences in the serum lipids profile, body fat distribution, HOMA-beta, HOMA
      IR, and DeltaI(30)/DeltaG(30) between these two groups. CONCLUSION: The excursion
      of blood glucose is greater in the FDRs of T2DM patients. CGMS is more sensitive
      to discover such change than OGTT.

PMID- 19595057
TI  - [Insulin release and daily glucose change in polycystic ovary syndrome women with
      normal glucose tolerance].
AB  - OBJECTIVE: To evaluate the characteristics of daily glucose change, insulin
      sensitivity, and insulin release in polycystic ovary syndrome (PCOS) women with
      normal glucose tolerance. METHODS: Oral glucose tolerance test (OGTT) with 75 g
      glucose was conducted on 20 PCOS women with normal glucose tolerance and 20 age
      matched healthy women with normal menstruation. Before the glucose uptake and 30,
      60, and 120 min after samples of venous blood were collected to detect the blood
      glucose and insulin. Continuous glucose monitoring system (CGMS) was used to
      monitor the glucose concentration of subcutaneous interstitial fluid so as to
      reflect the blood glucose level. Mean blood glucose level (MBG) and its standard
      deviation (SDBG), mean amplitude of glycemic excursion (MAGE), peak level of
      postprandial plasma glucose as well as its peaking time during a 48-hour period
      CGMS were calculated. Stumvoll first-phase and second-phase (1st PH and 2nd PH)
      insulin release during OGTT were evaluated by Stumvoll formula, whereas baseline
      insulin release by HOMA-B. Insulin sensitivity index (ISI) was evaluated by
      Cederholm formula. RESULTS: (1) The 1-hour and 3-hour plasma glucose levels
      during OGTT of the PCOS group were higher than those of the control group (P <
      0.01 and P < 0.05 respectively). The fasting insulin level and insulin levels 30,
      60, 120, and 180 min after the glucose uptake during OGTT of the PCOS group were
      all significantly higher than those of the control group (all P < 0.01). (2) The
      daily MBG, SDBG, and MAGE of the PCOS group were (5.43 +/- 0.44), (0.66 +/-
      0.24), and (1.46 +/- 0.47) mmol/L respectively, all similar to those of the
      control group [(5.3 +/- 0.5), (0.67 +/- 0.27), and (1.7 +/- 0.7) mmol/L
      respectively, all P > 0.05]. The peaking time of post-breakfast plasma glucose
      level of the PCOS group was (40 +/- 18) min, significantly longer than that of
      the control group [(30 +/- 10) min, P < 0.05]. (3) The ISI of the PCOS group was
      64 (59 - 81), significantly lower than that of the control group [95 (78 - 102),
      P < 0.01]. The Stumvoll 1st PH and 2nd PH insulin release levels of the PCOS
      group were 1779 (1411 - 2194) mU/L and 440 (361 - 545) mU/L respectively, both
      significantly higher than those of the control group [1217 (1056 - 1477) and 320
      (283 - 375) mU/L respectively, P < 0.01 and P < 0.05]. CONCLUSION: With normal
      glucose tolerance, the PCOS women show (1) a backwardly-shifted peak of glucose 
      stimulated insulin secretion, (2) an abnormal mode of daily glucose change
      characterized by a delayed peak of post-breakfast plasma glucose level, and (3)
      significant decrease of peripheral insulin sensitivity with compensated increase
      of insulin secretion.

PMID- 19595058
TI  - [Relationship between glucose fluctuation and beta cell function in patients with
      diabetes].
AB  - OBJECTIVE: To study the relationship between the glucose fluctuation and beta
      cell function in the diabetes mellitus (DM) patients. METHODS: Sixty hospitalized
      DM patients, 27 males and 33 females, aged (59 +/- 14), with a course of DM (8 +/
      8) years, underwent dynamic blood glucose monitoring by continuous glucose
      monitoring system (CGMS). Arginine stimulation test was conducted to detect the
      blood glucose and C peptide. Blood lipids were measured by automatic chemistry
      analyzer. The relations among fast plasma glucose (FPG), glycated hemoglobin
      (HbA1c), mean glucose concentration (MBG), mean amplitude of glycemic excursion
      (MAGE), and incremental value of C peptide (DeltaCP) were studied. RESULTS: (1)
      The subjects were divided into five subgroups by HbA1c, 24 h CGMS profiles showed
      that a progressive deterioration of the glycemic profiles from group 1to 5
      associated with increasing levels of HbA1c. The FPG levels were not significantly
      different between the group of HbA1c < 6.5%, and the group of 6.5% < or = HbA1c <
      7%, but the postprandial blood glucose of the latter group was higher than that
      of the former group. The CGMS curve shifted upward along with the increase of
      HbA1c level. (2) After adjustment for sex, age, and diabetes duration, positive
      correlation was found between HbA1cw and FPG, MBGw and FPG, MBG and HbA1c, MAGE
      and HbA1c, and MBG and MAGE (r = 0.67, 0.66, 0.63, 0.44, 0.39, all P < 0.01), and
      FPG and MAGE (r = 0.31, P < 0.05). (3) After adjustment for sex, age, and
      diabetes duration, the DeltaCP was negatively correlated with FPG, HbA1c and MAGE
      (r = -0.30, P < 0.05; r = -0.39, -0.42, all P < 0.01). MBG was not significantly
      correlated with DeltaCP (P > 0.05). (4) There was no significant differences in
      the DeltaCP level when HbA1c < 7%, but decreased when HbA1c > or = 7%. (5)
      Stepwise regression analysis demonstrated that MAGE firstly entered the equation
      and DeltaCP was predicted by MAGE, total cholesterol, and HbA1c when DeltaCP was
      regarded as dependent variable and age, diabetic duration, BMI, waist-to-hip
      ratio, blood pressure, MBG, MAGE, FPG, HbA1c, and blood lipid were regarded as
      independent variable (adjusted R(2) = 0.305, P < 0.01). CONCLUSION: Glucose
      fluctuation deteriorates the beta cell function much more than sustained
      hyperglycemia does.

PMID- 19595059
TI  - [Characteristics of glycemic excursion in different subtypes of impaired glucose
      intolerance].
AB  - OBJECTIVE: To investigate the characteristics of glycemic excursion of different
      subtypes of glucose tolerance. METHODS: Assessed by oral glucose tolerance test
      (OGTT) repeated twice, 81 individuals were divided into 4 groups: normal glucose
      tolerance (NGT, n = 18), isolated impaired fasting glycemia (IFG, n = 12),
      isolated impaired glucose tolerance (IGT, n = 19), combined IFG/IGT (n = 11), and
      newly diagnosed type 2 diabetes mellitus (T2DM, n = 21). And then continuous
      glucose monitoring system (CGMS) was used for 72 hours to monitor the blood
      glucose (BG) level before drug intervention. RESULTS: (1) The levels of largest
      amplitude of glycemic excursions (LAGE), mean blood glucose (MBG), and standard
      deviation of mean level of blood glucose fluctuation (SDBG) increased gradually
      with the deterioration of glucose tolerance. The mean amplitude of glucose
      excursion (MAGE) readout of the IGT group was (3.2 +/- 1.2) mmol/L, significantly
      higher than that of the NGT group [(1.6 +/- 0.5) mmol/L, P < 0.05], and
      significantly lower than that of the T2DM group [(5.2 +/- 1.9) mmol/L, P < 0.05].
      The level of frequency of glucose excursion (FGE) decreased along with the
      decrease of glucose tolerance: NGT group [(6.1 +/- 3.4)] > IGT/IFG group [(5.5 +/
      2.5)] > T2DM group [(4.8 +/- 1.8)]. Among the three components of IGR, the IGT
      group showed highest MAGE (3.2 +/- 1.2) mmol/L and lowest FGE level (4.9 +/-
      1.8). (2) The level of absolute mean of daily difference (MODD) increased in the
      following order: NGT group [(0.8 +/- 0.3) mmol/L], IGT group [(1.1 +/- 0.4)
      mmol/L], IFG/IGT group [(1.2 +/- 0.4) mmol/L], and T2DM group [(2.0 +/- 1.0)
      mmol/L] (all P < 0.05). (3) The fasting glucose level deteriorated the most
      rapidly in the IFG group, while it reached the highest postprandial peak in the
      IFG/IGT group. The blood glucose curve increased along the order of NGT, I-IGT,
      IFG/IGT, IFG, and T2DM. (4) When the level of glycosylated hemoglobin (HbA1c)
      level was less than 7%, the fasting phase of curve virtually coincided with each
      other among individual groups with different HbA1c levels; however, the
      postprandial peak separated slightly. When the HbA1C level was between 7.0% and
      7.9%, the postprandial peaks of individual groups with different HbA1c levels
      dispersed markedly. When the HbA1c level was higher than 8%, the fasting blood
      glucose curve moved upwards significantly with increasing postprandial excursion.
      CONCLUSION: (1) With the deterioration of glucose regulation, the intraday and
      day-to-day blood glucose excursions become increasingly fluctuant. (2) The
      amplitude of glycemic excursion is lower in the NGT group than in the T2DM group,
      however, the frequency of glycemic excursion is higher in the NGT subject than in
      the T2DM subjects. The glucose excursion profile of the IGR subjects is between
      the NGR and T2DM subjects. (3) The characteristics of glucose excursion of the
      IGT group are similar to those of the T2DM group, and the characteristics of the
      IFG group are similar to those of the NGT group. (4) The loss of postprandial
      glycemic control precedes evident deterioration in fasting phase of IGR.

PMID- 19595060
TI  - [T cell proliferative response and antibody formation to citrullinated collagen
      type II in patients with rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the T cell proliferative response and antibody
      formation to citrullinated collagen type II (Cit-CII) in patients with rheumatoid
      arthritis (RA), and explore whether autoreactive T cells responding to Cit-CII
      plays a role in the pathogenesis of RA. METHODS: Arginine residues of bovine
      collagen type II (CII) were converted to citrulline residues by peptidylarginine
      deiminase (PAD). Peripheral blood samples were collected from 34 RA patients, and
      18 sex- and age-matched controls, including 6 osteoarthritis patients and 12
      healthy blood donors. Peripheral blood mononuclear cells (PBMCs) were isolated
      and cultured with Cit-CII, CII, or fetal bovine serum RPMI 1640 fluid,
      phytohemagglutinin (PHA), or citrullinated buffer as controls. Cellular
      reactivity levels against Cit-CII and CII were investigated by measuring the
      proliferation of PBMCs to calculate the stimulation index (SI). ELISA was used to
      detect the presence of antibodies against Cit-CII and CII. RESULTS: The positive
      rate of T cell proliferative response to Cit-CII of the RA group was 32.4%
      (11/34), significantly higher than that of the control group (0, P < 0.05). The
      positive rate of T cell proliferative response to CII of the RA group was 35.3%
      (12/34), significantly higher than that of the control group (11.1%, P < 0.05).
      Interestingly, Cit-CII could not elicit a better T cell proliferative response
      than CII did. In the RA patients, the anti-Cit-CII antibody positive rate was
      52.9% (18/34), significantly higher than that of the anti-CII antibody positive
      rate [32.4% (11/34), P < 0.05). The serum IgG anti-CII antibody positive rate of
      the patients with positive T cell responses to CII was 58.3% (7/12),
      significantly higher than that of the patients with negative T cell responses to
      CII [18.2% (4/22), P < 0.05]. The serum IgG anti-CII antibody positive rate of
      the patients with positive T cell responses to Cit-CII was 72.7% (8/11),
      significantly higher than that of the patients with negative T cell responses to
      Cit-CII [43.5% (10/23), P < 0.05]. CONCLUSION: The recognition of Cit-CII by
      circulating IgG antibodies is a RA-specific serological phenomenon. The formation
      of CII antibody in the RA patients may be related to B cell activation mediated
      by CII specific T cells. The role of Cit-CII in RA cellular immune need be
      further studied.

PMID- 19595061
TI  - [Genetic counseling and instruction of marriage for deaf young people: study of
      115 cases].
AB  - OBJECTIVE: To invesigate the molecular pathogenesis of deafness among the youth
      by means of genetic testing so as to provide pre-marriage genetic counseling and
      instruction for the deaf youth. METHODS: 217 deaf young people, 126 males and 91
      females, aged 18.9 (16 - 26), from Yunnan and Guizhou provinces, underwent
      history taking, auditory testing, and collection of peripheral blood samples.
      Genomic DNA and mitochondrial DNA were extracted to undergo sequence analysis of
      the entire gene GJB2, common point mutation of SLC26A4 gene, and mutation of
      mtDNA A1555G. Genetic prediction and marriage instruction were provided to each
      subject based on these results. RESULTS: Twenty-three of the 117 persons (10.5%),
      13 males and 10 females, were mtDNA A1555G mutation carriers and they were
      instructed that they, their maternal relatives, and the offspring of the female
      carriers, should they be born, should strictly avoid the administration of amino
      glycoside antibiotics. Twenty eight of the 115 persons (12.9%), were confirmed to
      carry homozygous or compound GJB2 mutations, 5 individuals (2.3%) carried
      heterozygous GJB2 mutation, 19 (8.8%) carried homozygous or compound SLC26A4
      mutations, and one (0.5%) carried heterozygous SLC26A4 mutation. The suggestion
      for them was to avoid getting married with deaf partners caused by the same deaf
      gene or with individuals carrying mutations in the same deaf gene. Meanwhile,
      suggestions such as avoiding aggressive exercises and head injury were provided
      to the deaf young people with SLC26A4 mutations. CONCLUSION: Genetic testing can
      provide more accurate and useful genetic counseling and instruction to deaf young
      people for their partner selection and eugenics.

PMID- 19595062
TI  - [Hard nut to crack in diagnosis of pituitary hyperplasia secondary to primary
      hypothyroidism and reasons of misdiagnosis].
AB  - OBJECTIVE: To analyze the difficulty in diagnosis of pituitary hyperplasia
      secondary to primary hypothyroidism and reasons of misdiagnosis. METHODS: Ten
      patients with clinical manifestations of primary hypothyroidism, 3 males and 7
      females, aged 7 - 26, underwent MR imaging and serum hormone examination before
      and after thyroid hormone replacement therapy. T1-weighted images without and
      with contrast material enhancement in sagittal and coronal planes were obtained.
      Serum free triiodothyronine, free thyroxine, thyrotropic-stimulating hormone and
      prolactin (PRL) levels were measured. RESULTS: Obvious symmetrical enlargement of
      the pituitary gland with homogeneous signal intensity was revealed by MRI in all
      the patients. The height of the pituitary ranged 1.2 - 2.2 cm. The pituitary
      glands appeared homogeneously enhanced after Gd-DTPA administration. After 3 - 6
      months of L-thyroxin replacement therapy, follow-up MRI showed that the pituitary
      glands reduced in size markedly in 9 cases, and the plasma thyroxine, TSH, and
      PRL levels of these 9 cases turned normal. One patient was misdiagnosed as with
      macroadenoma and was treated with gamma knife, resulting in permanence
      hypothyroidism. CONCLUSION: Symmetrical enlargement of pituitary gland with
      homogeneously enhancement on MRI has great diagnostic value in pituitary
      hyperplasia with primary hypothyroidism. Thyroid hormone replacement therapy can
      cause regression of the enlarged pituitary, thus avoiding unnecessary surgery.

PMID- 19595063
TI  - [Effects and toxicity of neoadjuvant chemotherapy with vinorelbine and cisplatin
      in treatment of operable breast cancer previously non-responsive to
      anthracyclines and taxanes-containing regimen: analysis of 19 cases].
AB  - OBJECTIVE: To evaluate the short-term effects and toxicity of vinorelbine
      combined with cisplatin (NP) as a neoadjuvant chemotherapy regimen in treatment
      of operable breast cancer non-responsive to the combination of anthracyclines and
      taxanes. METHODS: Nineteen breast cancer patients, all female, who failed to
      achieve complete remission (CR) or partial remission (PR) to the combination of
      anthracyclines and taxanes as neoadjuvant regimen were treated with 2 cycles of
      NP regimen (vinorelbine 25 mg/m(2), on days 1 and 8 and cisplatin 70 mg/m(2), on
      days 1 and 3, both by intravenous infusion, as a cycle). The clinical objective
      response was evaluated with dynamic contrast-enhanced MRI of the breast before
      operation and the pathological response was evaluated by pathological
      examination. The toxicity of the NP regimen was evaluated according to National
      Cancer Institute-Common Toxicity Criteria v.3.0. RESULTS: The CR + PR rate of the
      NP regime was 52.6% (10/19), and pathological response (G(2) + G(3) + G(4) +
      G(5)) was found in 17 cases (89.5%, 17/19). The most common toxicities were
      neutropenia and nausea/vomiting. These toxicities were reversible and did not
      cause death. CONCLUSION: A well-tolerated and effective regimen for breast cancer
      patient who fail to respond to the combination of anthracyclines and taxanes
      neoadjuvant chemotherapy, the NP regimen can be considered as an effective choice
      of second-line regimen. It can be considered as an effective choice of second
      line regimen.

PMID- 19595064
TI  - [Spatio-temporal expression of connexion (Cx) 40 and Cx45 in Cx43 knockout
      embryonic mouse hearts].
AB  - OBJECTIVE: To investigate the spatio-temporal expression of connexin (Cx) 40 and
      Cx45 genes in Cx43 knockout embryonic mouse hearts. METHODS: Cx43 knockout
      heterozygous mice were raised. PCR was performed to identify genotypes of their
      offsprings. The homozygote (Cx43-/-) was used for study and the wild type
      (Cx43+/+) was used as control. Immuno-histochemistry was used to detect the Cx40
      and Cx45 expression in different parts of the fetal hearts at the embryonic days
      (EDs) 10.5, 11.5, 12.5, 13.5, 14.5, and 15.5, respectively. SCIM microscopic
      image analytic system was used for quantitative analysis of staining intensity.
      RESULTS: (1) Cx40 expression was detected in ventricles of Cx43+/+ fetal heart as
      early as ED10.5 with the intensity represented by A value of 8.6. Subsequently it
      was distributed in the atria and ventricles with the peak expression observed at
      ED14.5 (A value = 94.8), and faded afterwards. Less Cx40 expression was observed
      in the Cx43-/- fetal hearts as compared with Cx43+/+ although its expression
      pattern was similar in both groups. (2) Cx45 expression was detected in
      ventricles at ED 10.5 (A value = 20.0). It was subsequently distributed in the
      atria and ventricles with the peak expression observed at ED12.5 (A value =
      49.6), and then faded. Less Cx45 expression was observed in the Cx43-/- fetal
      hearts as compared with Cx43+/+ although its expression pattern was similar as
      well in both groups. CONCLUSION: Down-regulated expression of the genes Cx40 and
      Cx45 may be associated with the abnormal heart development in Cx43 knockout
      animals.

PMID- 19595065
TI  - [Chiral selectivity in differentiation of lung cancer A549 cell to vascular
      endothelial cells after drug resistance induced by D-or L-methotrexate
      enantiomers].
AB  - OBJECTIVE: To study the chiral selectivity in vascular endothelial
      differentiation in drug resistant lung cancer cells induced by high-dose L- or D
      methotrexate (MTX) enantiomer. METHODS: Human lung cancer cells of the line A549
      were co-cultured with high-dose (15 micromol/L) L- or D-MTX enantiomer so as to
      develop cancer cells resistant to MTX. MTT method was used to detect the drug
      resistant index. Flow cytometry was used to detect the expression of CD44, a
      transmembrane glycoprotein reflecting the migration ability of cells, CD31, a
      marker of vascular endothelium, and P-170 protein. Fifteen BALB/c nude mice were
      inoculated with the parent A549 cells, L-MTX-resistant A549 cells induced by L
      MTX enantiomer, and D-MTX-resistant A549 cells induced by D-MTX enantiomer. Four
      weeks later the mice were killed to take out the tumor masses.
      Immunohistochemistry with CD34 staining was used to detect the microvascular
      density (MVD). RESULTS: The drug resistant index of the D-MTX induced drug
      resistant A549 cells was 20.1 +/- 2.3, significantly higher than that of the L
      MTX-induced cells (12.4 +/- 1.2, P = 0.000). The CD44 positive rate of the D-MTX
      induced A549 cells was 97.0% +/- 0.9%, not significantly different from that of
      the L-MTX-induced A549 cells (96.7% +/- 1.4%, P = 0.544). The CD31 positive rate
      of the D-MTX induced A549 cells was 91.9% +/- 3.2%, significantly higher than
      that of the L-MTX-induced A549 cells (32.9% +/- 8.0%, P = 0.000). The P-170
      protein positive rate of the parent cells was 85.5% +/- 4.6%, and the P-170
      protein positive rate of the D-MTX-induced A549 cells was 87.0% +/- 8.9%,
      significantly higher than that of the L-MTX-induced cells (71.5% +/- 8.2%, P =
      0.002). The MVD of the D-MTX-induced cells was 55.9 +/- 11.9, significantly
      higher than that of the L-MTX-induced cells (7.2 +/- 1.7, P = 0.000). MVD was
      significantly positively correlated with the CD31 level (r = 0.462, P = 0.007),
      and not correlated with P-170 protein and CD34 levels. CONCLUSION: The MTX
      enantiomers have different chiral selectivity on human lung cancer cell, D-MTX
      resistant cells shows a potential of differentiation from cancer cells to
      vascular endothelial cells. D-MTX is not be regarded just as a pollutant in the
      drug MTX, MTX with single enantiomer (L-MTX) should be selected clinically so as
      to decrease the side effects of D-MTX.

PMID- 19595066
TI  - [Glutamine inhibits interleukin-1beta induced nitric oxide production and
      inducible nitric oxide synthase expression: experiment with cultured rat
      hepatocytes].
AB  - OBJECTIVE: To investigate the influences of glutamine (Gln) on nitric oxide (NO)
      production and inducible nitric oxide synthase (iNOS) expression in hepatocytes
      activated by interleukin (IL)-1beta, a pro-inflammatory cytokine. METHODS:
      Primary hepatocytes were isolated from SD rats by in situ collagenase perfusion,
      and cultured with normal saline (NS), IL-1beta (1 nmol/L) alone, IL-1beta (1
      nmol/L) with Gln of 2, 5, or 10 mmol/L for 24 hours. The concentration of NO in
      the supernatant was detected by biochemical method. Western blotting and real
      time quantitative reverse transcription PCR (RT-PCR) were used to detect the
      protein and mRNA expression of iNOS in the hepatocytes. The binding activity
      nuclear factor kappa B (NF-kappaB) in hepatocytes cellular localization of
      nuclear factor kappa B (NF-kappaB) in the nuclei of hepatocytes was investigated
      using electrophoretic mobility shift assay (EMSA). RESULTS: The average NO
      concentration of the IL-1beta group was 72.7 micromol/L, significantly higher
      than that of the NS group [(41.7) micromol/L, P < 0.01]. The NO concentrations in
      the supernatant of the IL-1beta + Gln 5 and 10 mmol/L groups were 52.9 and 44.4
      micromol/L respectively, both significantly higher than that of the NS group
      (both P < 0.05). The iNOS mRNA and protein expression levels of the IL-1beta
      group were 11 and 2.5 times as those of the NS group (both P < 0.05). Gln dose
      dependently decreased the iNOS mRNA and protein expression levels in the
      hepatocytes. The NO concentration and levels of iNOS mRNA and protein expression
      in the hepatocytes of the Gln 10 mmol/L group were not significantly different
      from those of the NS group. The NF-kappaB levels in the nuclei of hepatocytes of
      the IL-1beta group, 3 IL-1beta + Gln group, and only Gln group were all higher
      than that of the NS group. CONCLUSION: Glutamine down-regulates the iNOS gene
      over-expression mediated by IL-1betain hepatocytes through an NF-kappaB
      independent pathway.

PMID- 19595067
TI  - [Therapeutic effects of emodin on acute cholestatic hepatitis and mechanism
      thereof: experiment with rats].
AB  - OBJECTIVE: To investigate the therapeutic effects of emodin on acute cholestatic
      hepatitis and mechanism thereof. METHODS: 96 SD rats were randomly divided into 4
      groups to be treated with emodin, ursodeoxycholic acid, dexamethasone, or normal
      saline respectively for 4 days. On the 5th day gastric perfusion of alpha
      naphthylisothiocyanate (ANIT) was performed to establish models of cholestatic
      hepatitis. 4 - 6 hours after the establishment of model the above mentioned
      agents were given continuously. 24, 48, and 72 hours after the model
      establishment blood samples were collected from abdominal aorta to examine the
      total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma
      glutamyltransferase (GGT), and total bile acid (TBA). Specimen of liver was
      collected to undergo pathological examination. PCR was used to detect the mRNA
      expression of cytokine-induced neutrophil chemoattractant 1 (CINC-1) and
      macrophage inflammatory protein 2(MIP-2), and Western blotting was used to detect
      the protein expression of intercellular adhesion molecule 1 (ICAM-1). Twenty-four
      rats treated with NS only were used as controls. RESULTS: The pathological
      changes of behaviors and liver of the emodin and ursodeoxycholic acid groups were
      all remarkably milder than those of other model groups. The levels of TB [(32.8
      +/- 3.7) micromol/L, (61.0 +/- 16.4) micromol/L, (10.8 +/- 4.5) micromol/L], DB[
      (26.03 +/- 3.10) micromol/L, (49.40 +/- 18.16) micromol/L, (8.04 +/- 3.03)
      micromol/L], and ALT [(314 +/- 50) U/L, (664 +/- 97) U/L, (200 +/- 60) U/L], at
      the time points 24, 48, and 72 hours, the 48 and 72 hours AST levels, the 48
      hours ALP level, the 72 hours GGT level, and the 48 and 72 hours TBA levels of
      the emodin group were all significantly lower than those of the model group (all
      P < 0.05). The 24 and 48 hours TB levels, 24 hours DB and ALT, and 24, 72 hours
      TBA levels of the emodin group were all significantly lower than those of the
      ursodeoxycholic acid group (all P < 0.05). The 24, 48 hours TB and TBA levels,
      and the ALT, AST and GGT levels at all time points of the emodin group were all
      significantly lower than those of the dexamethasone group (all P < 0.05). The
      CINC-1 and MIP-2 mRNA expression levels and ICAM-1 protein expression levels at
      all time points of the emodin group were all significantly lower than those of
      the model group (all P < 0.05). CONCLUSION: Decreasing the levels of TB, DB and
      ALT in particular, emodin has a protective effect on cholestatic hepatitis. Its
      effects are quicker than ursodeoxycholic acid, and it has better effects on ALT,
      AST GGT, and TBA than dexamethasone. These effects may be due to inhibition of
      the activation of CINC-1, MIP-2, and ICAM-1.

PMID- 19595075
TI  - [Progress in the genetic factors of inflammatory bowel disease].

PMID- 19595068
TI  - [Nephrotoxicity of tacrolimus and preventive effect of diltiazem: experiment with
      rats].
AB  - OBJECTIVE: To study the nephrotoxicity tacrolimus (FK506) at the therapeutic dose
      the preventive effect of diltiazem (Dil), a calcium antagonist against the FK506
      induced pathological changes. METHODS: 24 Sprague-Dawley male rats were randomly
      divided into 4 equal groups: cyclosporine A (CsA) group, undergoing treatment of
      CsA at the therapeutic dose after kidney transplantation (25 mg x kg(-1) x d(-1))
      for 4 weeks, FK506 group treated with FK506 (0.8 mg x kg(-1) x d(-1)), FK506 +
      Dil group treated with FK506 (0.8 mg x kg(-1) x d(-1)) and Dil at the dose of 8
      mg x kg(-1) x d(-1), and control group. Four weeks later body weight was measured
      and 24 h urine sample was collected. Then the rats were killed. Their kidneys
      underwent light and transmission electron microscopy. RESULTS: The body weight ad
      weight gain, and the weights of both kidney of the CsA group were all
      significantly lower than those of the other 3 groups (all P < 0.05), and there
      were not significant differences in there parameters among the other 3 groups.
      The serum creatinine levels of the FK506 and CsA groups were (36.0 +/- 2.6) and
      (34.2 +/- 4.5) micromol/L respectively, both significantly higher than those of
      the FK506 + Dil and control groups [(28.5 +/- 2.1) and (29.2 +/- 3.428)
      micromol/L respectively, all P < 0.05], however, there was no significant
      difference between the FK506 + Dil and control groups. The creatinine clearance
      rate of the FK506 and CsA groups were (0.63 +/- 0.45) and (0.58 +/- 0.39) ml x
      min(-1) x 100 g(-1) respectively, significantly lower than those of the FK506 +
      Dil and control groups [(1.55 +/- 0.91) and (1.02 +/- 0.62) mlxmin(-1) x 100 g(
      1) respectively, all P < 0.05]. Pathological examination showed epithelial cell
      cloudy swelling and vacuolization and interstitial fibrosis in the renal tubules,
      mitochondria swelling and vacuolization in renal tubular epithelial cells, renal
      arteriole hyalinization, and foot cell conjugation glomerulus, mitochondria
      swelling and vacuolization in the FK506 and CsA groups, and such changes were
      relatively mild in the FK506 + Dil group. CONCLUSION: FK506 at renal
      transplantation therapeutic dose, as well as CsA, induces pathological changes in
      renal tissues and ultrastructural organization. Dil is able to prevent FK506
      induced these pathological changes.

PMID- 19595077
TI  - [PD-1 up-regulation influenced apoptosis of HBV-specific CD8 T cells in patients
      with acute resolved hepatitis B].
AB  - OBJECTIVE: Programmed death-1 (PD-1) up-regulation can impair virus-specific
      CD8(+) T-cell responses during chronic viral infection. Whether PD-1 affects
      virus-specific CD8 T cells in humans with acute hepatitis B virus (HBV) infection
      remains unknown. This study aimed to characterize the PD-1 expression during
      acute hepatitis B (AHB), and further addressed how PD-1 regulates the apoptosis
      of CD8(+) T cells in this disease. METHODS: PD-1 expression on HBV env-183-191-,
      env-335-343- and CMV pp65-specific CD8(+) T cells were quantitatively analyzed by
      flow cytometry in peripheral blood from 15 HLA-A2-positive AHB patients. The
      spontaneous apoptosis indicated by annexin V expression was performed for
      analyses of the impact of PD-1 expression. We also confirmed the effects of PD
      1/PD-L1 pathway on the in vitro apoptosis of CD8(+) T cells through PD-1 blockade
      assay. RESULTS: PD-1 expression on HBV-specific CD8(+) T cells was significantly
      up-regulated compared with CMV-specific CD8(+) T cells in the early phase of
      acute HBV infection. High levels of PD-1 expression significantly correlated with
      the apoptosis of HBV-specific CD8(+) T cells. Blockade of PD-1 ligation using
      anti-PD-L1 rescued the HepG2.215-induced CD8(+) T cell apoptosis. CONCLUSION: PD
      1/PD-L1 inhibitory pathway is actively involved in the apoptotic regulation of
      HBV-specific CD8(+) T cells at early phase of acute HBV infection, and high PD-1
      expression by HBV-specific CD8(+) T cells appear to efficiently temper liver
      damage.

PMID- 19595078
TI  - [Finite element analysis on stress change of lumbar spine].
AB  - OBJECTIVE: To build a 3D finite element model of whole lumbar spine and verify
      its efficiency and analyze the biomechanical change of L3-4 motion segment.
      METHODS: L1-L5 segment data were obtained from computed tomography (CT) scans of
      the lumbar spine of a 40-year-old man with no abnormal findings. A three
      dimensional finite element model of the human whole lumbar spine was built in the
      Mimics and the ABAQUS software. The model was composed of bony vertebrae,
      articulating facets, intervertebral disc and associated ligaments. The basic
      stress analysis of L3-4 motion segment was made under the considerations of
      different material properties of bone, ligaments and facet joints contacting
      frictional property. The stress on annulus fiber, nucleus pulposus, endplate and
      facet joints under axial pressure (0.3 MPa, 0.5 MPa, 1.0 MPa, 2.0 MPa & 4.0 MPa)
      were analyzed. RESULTS: A three-dimensional finite element model of human L3-L4
      motion segment has 272, 619 elements, the stresses were higher in the posterior
      of annulus fiber, the Max pressure stress (S33) distributed in nucleus pulposus
      and the center of endplate. The stresses increased as axial pressure rose.
      CONCLUSION: 3D finite element model of whole lumbar spine and L3-4 motion segment
      were established successfully and the stress analyses were feasible and reliable.

PMID- 19595079
TI  - [Surgical options and result analyses in adult degenerative lumbar scoliosis].
AB  - OBJECTIVE: To investigate the clinical and radiographic outcomes for varying
      degrees of degenerative lumbar scoliosis using different surgical options with a
      minimal 5-year follow-up. METHODS: From May 1998 to November 2002, 31 patients
      with degenerative lumbar scoliosis underwent operations at our hospital. The mean
      age of 19 females and 12 males was 55.8 years old (range: 45 to 71). All patients
      were divided into 4 groups: Group A, mild coronal deformity with obvious sagittal
      deformity, 13 cases; Group B, obvious coronal deformity with mild sagittal
      deformity; Group C, both significant coronal and sagittal deformities; Group D,
      both mild coronal and sagittal deformities. Posterior decompression, internal
      fixation and bone graft fusion were performed in Groups A, B and C. And posterior
      decompression was performed in Group D. All patients were followed up for at
      least 5 years. Patients answered the Oswestry low back pain disability
      questionnaire at pre-operation, and 1 year, 5 year post-operation. RESULTS:
      Thirty patients were followed up for the whole process. According to Cobb's angle
      methods, there was great post-operative improvement for patients with internal
      fixation (Groups A, B, C) while there was no significant difference for patients
      with posterior decompression at pre-and post-operation. After surgery, the
      average Oswestry Disability Index score in the patients with internal fixation
      (Groups A, B, C) was significantly lower than the preoperative score (25.8 vs
      58.0; P < 0.001). However there was statistical difference for patients with
      internal fixation between 1 year and 5 year postoperatively. No perioperative
      death or major medical complications occurred. Ten patients had adjacent segment
      degeneration. CONCLUSIONS: The surgical aim for adults with a spinal deformity is
      to achieve a stable, balanced and pain-free spine. Surgical treatments should
      consist of decompression and fusion with segmental instrumentation to avoid
      instability and curb progression. Despite the complexity of adult lumbar
      degenerative scoliosis, it might improve the quality of life for patients by
      choosing an appropriate operation option on the basis of varying degrees of
      lumbar deformity.

PMID- 19595080
TI  - [Etiological, clinical and imaging characters of reversible posterior
      encephalopathy syndrome].
AB  - OBJECTIVE: To elucidate the clinical and imaging characters of reversible
      posterior encephalopathy syndrome (PRES) and to discuss the etiological factors
      and the probable pathogenesis. METHOD: Retrospective analysis of basal diseases,
      clinical manifestations and imaging characters of 13 PRES patients was conducted
      with follow-ups. RESULTS: The common associated diseases are various kinds of
      kidney disease and renal inadequacy, eclampsia of gravidity and postpartum,
      connective tissue disease and immunosuppressives, et al. The main clinical
      manifestations are headache, convulsion, poor vision, changes of psychology or
      consciousness. The radiological findings are multifocal, symmetrical and
      posteriorly distributed in the cerebral hemispheres involving bilateral grey and
      white matter abnormalities in occipital, parietal and frontal regions. The
      majority of patients with PRES have an excellent prognosis. CONCLUSION: The
      etiological factors and pathogenesis of PRES are different and not all of them
      are reversible. Thus it is decisive to take specific and appropriate measures.

PMID- 19595081
TI  - [Quantitative analysis of regional cerebral blood flow in elderly with white
      matter lesions].
AB  - OBJECTIVE: To observe whether the severity of white matter lesions (WML) is
      related to ischemia in elderly. METHODS: WML were divided into 2 categories
      (centrum semiovale and periventricular regions) and four grades (grade 0, grade
      1, grade 2 and grade 3) according to the severity of WML showing on the FLAIR
      sequence of MRI using modified Fazekas scale. The values of regional cerebral
      blood flow (rCBF) within WML and other brain regions were measured using Xenon
      contrast CT. RESULTS: Mean rCBF (ml x 100 g(-1) x min(-1)) within lesions around
      periventricular areas, in right and left centrum semiovale were 20.8 +/- 2.8,
      22.3 +/- 1.9 and 22.2 +/- 2.1 in grade 0; 20.3 +/- 2.5, 21.3 +/- 1.0 and 21.0 +/-
      1.8 in grade1; 16.3 +/- 2.0, 15.6 +/- 1.7 and 15.9 +/- 0.9 in grade 2; 14.1 +/-
      2.6, 14.5 +/- 2.2 and 14.2 +/- 1.9 in grade 3 respectively. The severity of WML
      is associated significantly with reduction of rCBF within lesions both in centrum
      semiovale and periventricular regions (all P < 0.05). There was no significant
      difference in rCBF values between grade 0 and 1, but significant differences
      existed between grade 0 and grades 2 and 3, between grade 1 and grades 2 and 3
      (all P < 0.05). Statistical significance also existed between the severity of
      white matter lesions and rCBF in bilateral temporal lobes and lentiform nucleases
      (P < 0.05). CONCLUSIONS: The severity of WML both in centrum semiovale and
      periventricular regions is associated significantly with reduction of rCBF within
      lesions.

PMID- 19595082
TI  - [Endoscopic therapy for obstructive hydrocephalus caused by cysts in the pathway
      of CSF circulation].
AB  - OBJECTIVE: To explore the process and technique of neuroendoscopic operation to
      treat obstructive hydrocephalus caused by cysts located in the pathway of CSF
      circulation. METHODS: The cine MRI examinations and endoscopic operations were
      taken to treat 30 cases with obstructive hydrocephalus. Among all the cases,
      there are 11 intraventricular cysts (8 lateral ventricular cysts, 4 fourth
      ventricular cysts), 4 suprasellar arachnoid cysts, 1 quadrigeminal cistern
      arachnoid cyst, 6 Dandy-Walker malformations and 8 posterior fossa arachnoid
      cysts. RESULTS: CSF dynamic of all patients improved to different extents post
      operation. It was observed that CSF passed through the stoma after ETV in all
      patients. The volume of 9 intraventricular cysts, 4 suprasellar arachnoid cysts,
      1 quadrigeminal cistern arachnoid cyst and 4 posterior fossa arachnoid cysts
      diminished for different degrees. There were no surgery-related serious
      complications or deaths. There were not cyst enlarged and stoma obstructed cases.
      CONCLUSIONS: Obstructive hydrocephalus caused by cysts in the pathway of CSF
      circulation is the optimal indication for neuro-endoscopic surgery. After
      resecting cyst partially, we should take the endoscopic third ventriculostomy to
      rebuild the passway of CSF and elevate the cranial compliance. Cine MRI and
      radionuclide cisternography are helpful to understand the CSF dynamic and
      absorption.

PMID- 19595083
TI  - [Clinical characteristics and ultra-structural features of skeletal muscle in
      mitochondrial cytopathies].
AB  - OBJECTIVE: To investigate the ultrastructural features of mitochondrial
      cytopathies and its diagnostic value. METHODS: Muscle biopsy specimens from 33
      cases of mitochondrial cytopathies were examined by routine pathological and
      electron microscopic examinations. RESULTS: The main pathologic changes included
      ragged red fibers in modified Gomori staining, hyper-intense staining myofibers
      in SDH, COX-negative fibers while dark counterstaining with SDH in COX/SDH double
      staining technique. Ultrastructural findings included subsarcolemmal and
      intramyofibrillar proliferation of mitochondria and the appearance of abnormal
      mitochondria, paracrystalline inclusions, concentric dystrophic cristae and
      excessive subsarcolemmal glycolipid compounds in subsarcolemmal. CONCLUSION: The
      presence of proliferation and abnormality of mitochondria, electro-dense granule
      and paracrystalline inclusions in mitochondria provide key diagnostic evidence
      for the diagnosis of this disease.

PMID- 19595084
TI  - [Gamma knife for elderly patients with large vestibular schwannomas: 11-year
      follow-up].
AB  - OBJECTIVE: To evaluate the effect of Leksell Gamma Knife (LGK) on elderly
      patients with large vestibular schwannomas (VS) and to summarize the indications
      for LGK in patients with large VS. METHODS: From July 1994 to July 2000, 50
      elderly patients (age range: 60.0 - 81.0 years) with large VS were treated by LGK
      as primary treatment modality. The maximal tumor diameter ranged from 31.0 to
      61.0 mm [mean, (36.0 +/- 6.1) mm] and mean tumor volume was (14.8 +/- 8.0) cm(3)
      (range, 7.5 - 54.0 cm(3)). The maximal dose irradiated to tumor ranged from 22.0
      to 28.0 Gy [mean: (25.0 +/- 1.6) Gy] and the mean tumor marginal dose was (12.3
      +/- 0.9) Gy (range, 9.5 - 14.0 Gy). The mean follow-up duration was (86 +/- 12)
      months (range: 68 - 138 months). RESULTS: Of the 50 patients with follow-up data,
      4 were deceased and 46 survived. Two patients with giant VS died at 6 and 9
      months post-LGK respectively because of tumor swelling. Another two patients died
      of stroke or heart attack at 3 years and 4 years after LGK respectively, but
      their tumors decreased in volume. Clinical response: hearing: 14 (28%) patients
      preserved useful hearing as pre-LGK; 32 patients had unchanged or deteriorated
      hearing. Facial palsy: two patients developed mild facial palsy at 4 and 8 months
      respectively, one of them recovered and another improved later. Seven patients
      developed hydrocephalus around 6 months post-LGK and had V-P shunt. Eighteen
      patients had deteriorated facial numbness because of tumor swelling, 15 of them
      improved 3 years later. Tumor response: in 46 surviving patients, 43 tumors
      decreased markedly in size, 2 tumors remained stable in volume, 1 tumor
      progressed at five years and had second LGK. In this series tumor control rate
      was 94% (47/50). CONCLUSION: LGK provides an effective treatment for some
      selected large VS (maximal diameter <or= 40 mm) in elderly patients, especially
      when the brain stem compression was not obvious and VS had non-enhanced area or
      small cysts within the tumor on contrast MRI.

PMID- 19595085
TI  - [Effects of mobilization of bone marrow stem cells on regenerative potential of
      cardiac tissues after myocardial infarction].
AB  - OBJECTIVE: To test the potential of bone marrow stem cells mobilized by
      granulocyte macrophage colony stimulating factor (GM-CSF) to promote regeneration
      of myocyte and neovascularization in a rat model of myocardial infarction.
      METHODS: A myocardial infarction model was created by ligation of the left
      anterior descending coronary artery in adult Sprague-Dawley rats. Then the
      infracted rats were randomly assigned to receive GM-CSF injection subcutaneously
      50 microg x kg(-1) x day(-1) as experimental group or receive saline injection as
      control group. Enumeration of CD(34)(+) stem cells in peripheral blood and bone
      marrow was performed by flow cytometric analysis. Histologic and
      immunohistological staining such as Factor VIII, Ki67 and PTAH staining
      (phosphotungstic acid hematoxylin) was performed to assess angiogenesis and
      myogenesis, calculate myocardial infarction size in the heart. RESULTS: The
      CD(34)(+) stem cells in the blood and bone marrow increased from Day 3, peaked
      between Day 7 (0.350% +/- 0.026%, 2.250% +/- 0.140%) and Day 14 (0.260% +/-
      0.022%, 2.060% +/- 0.110%) in experimental group compared with control group
      (0.170% +/- 0.015%, 1.240% +/- 0.064%) (P < 0.01), declined on Day 28 and no
      difference versus control group (P > 0.05). Immunohistological staining showed
      apparent neovasculature formation and much more Ki67 expression in the infracted
      regions in experimental group (313 +/- 10, 275 +/- 5) compared with control group
      (264 +/- 10, 207 +/- 10) (P < 0.05). The Ki67 positive cells in the experimental
      hearts were significantly positively correlated with CD(34)(+) stem cells in the
      blood and bone marrow (r = 0.961, P = 0.019, r = 0.975, P = 0.005). Ki67 and PTAH
      double staining showed that the Ki67 positive nucleoli overlay the lymphocytes,
      fibroblasts and endothelial cells but not myocytes. No significant decrease of
      infracted size occurred in experimental group (P > 0.05). CONCLUSIONS: Bone
      marrow and peripheral blood stem cells could be mobilized effectively by GM-CSF
      after myocardial infarction which could only promote neovascularization without
      myogenesis.

PMID- 19595086
TI  - [Experimental investigation of roles of STAT4 and SOCS3 in differentiation and
      cytokine secretion of T helper cells by RNA interference].
AB  - OBJECTIVE: To investigate the roles of signal transducer and activator of
      transcription 4 (STAT4) and suppressor of cytokine signaling 3 (SOCS3) in
      differentiation and cytokine secretion of T helper (Th) cells by separate
      silencing. METHODS: Th0 cells were induced to differentiate to Th1 or Th2 cells
      by interleukin 12 (IL-12) or interleukin 4 (IL-4). The mRNAs of STAT4 and SOCS3
      were silenced separately by small interfering RNA (siRNA) in Th0, Th1 and Th2
      cells and then the lymphocytes cultured in Th1 or Th2 medium with IL-12 or IL-4
      for another 48 h before cells and supernatants were collected for the detection
      of Th1 and Th2 type cytokines by reverse transcriptase polymerase chain reaction
      (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). By comparing different
      amounts of cytokines between before and after silencing the target mRNAs, the
      roles of STAT4 and SOCS3 in the differentiation and cytokine secretion in T
      helper cells were evaluated. RESULTS: Th1 type cytokine significantly decreased
      and Th2 type cytokine increased after silencing STAT4 in Th0 and Th1 cells;
      minimal changes were detected in both Th1 and Th2 type cytokines after silencing
      SOCS3. CONCLUSION: STAT4 mediates the IL-12-induced differentiation of T cells to
      Th1 subset and maintains the cytokine secretion of Th1 cells; STAT4 directly
      inhibits the development and cytokine secretion of Th2 cells; STAT4 deficiency
      results in impaired development and cytokines secretion of Th1 cells and the
      enhanced development and cytokines secretion of Th2 cells. SOCS3 has minimal
      effects on IL-12 or IL-4 induced differentiation and cytokine secretion of T
      helper cells.

PMID- 19595087
TI  - [Effects of ketamine and splenectomy on cognition and synaptic plasticity in
      hippocampus of senile rats].
AB  - OBJECTIVE: To study the effects of ketamine anesthesia and surgery on cognition
      and synaptic structure in hippocampus of senile rats. METHODS: Fifty-six rats
      aged 18 months were randomly divided into 3 groups: Groups C (control group), A
      (ketamine 40 mg/kg, i.p.) and O (ketamine anesthesia & splenectomy). Morris water
      maze test was used to observe cognition at Days 1, 3 & 7 after ketamine
      anesthesia or operation respectively. Accordingly Groups A and O were divided
      into 3 subgroup, i.e. A1, A3, A7 and O1, O3, O7. The time of Morris water maze
      test was recorded and the synaptic structure was measured in the polymorphic
      layer of the rat hippocampal field CA3. RESULTS: Compared to Group C, the latency
      period and swimming distance significantly increased in Groups A1, O1 and O3 (P <
      0.05), and the numbers passing the original platform decreased significantly in
      Groups O1 and O3 (P < 0.01). The latency period was significantly longer in Group
      O1 than that in Group A1 (P < 0.05) while the swimming distance was unchanged.
      Compared to Group C, the width of synaptic cleft (P < 0.01) increased, the length
      and area of postsynaptic densities (P < 0.05 or P < 0.01) as well as synaptic
      curvature (P < 0.01) decreased in Groups O1 and O3. The percentage of perforated
      synapses also decreased in Groups O1 and O3. CONCLUSION: Surgical injury can
      impair cognition of senile rats and the synaptic plasticity might be involved in
      postoperative cognitive dysfunction.

PMID- 19595088
TI  - [Comparative study on clearance dynamics of hepatitis B virion and cccDNA in
      blood].
AB  - OBJECTIVE: To confirm whether it is feasible to detect HBV cccDNA based on an
      analysis of its stability and clearance dynamics in the blood of ducks. METHODS:
      Twelve 1-week-old ducklings were randomized into group A and group B, and each
      duckling was intravenously injected with 1 milliliter of serum containing 1.2 x
      10(9) copies of HBV virion (group A) or plasmid pBS HBV 3.6 II (group B). At
      0.25, 2, 4, 6, 8, 12, 24 and 32 h post-injection, serum HBV DNA level in each
      duckling was quantified by Real-time fluorescent PCR. RESULTS: Both of HBV virion
      and plasmid pBS HBV 3.6 II could be detected from 0.25 h to 24 h after
      intravenous administration, and declined approximately by 1 log(10) every 2 hours
      within 8 h and was more slowly cleared at 8 h, and became undetectable at 32 h.
      Both of them are characteristic of one-phase exponential decay, as indicated by
      the relative index of the one-phase exponential curve ranging from 0.9593 to
      0.9976. The mean half-life of HBV virion and plasmid (cccDNA) was 4.536 +/- 0.769
      h (range: 3.5 - 5.4 h) and 4.5 +/- 0.8 h (range: 3.9 - 6.1 h) respectively. No
      significant difference was observed in the half-life between HBV virion and
      plasmid/cccDNA (t = 0.0523, P = 0.9593). CONCLUSIONS: HBV cccDNA is similar to
      HBV virion in its characteristics of clearance dynamics in blood. Thus it is
      feasible to detect serum HBV cccDNA. The clearance half-life of Hepatitis B virus
      in serum is not as long as previously believed at 1.0 - 1.2 d.

PMID- 19595096
TI  - [Several opinions on research of surgical treatment for cerebrovascular
      diseases].

PMID- 19595097
TI  - [Microsurgical techniques of middle cerebral artery aneurysms].
AB  - OBJECTIVE: To summarize the experience in surgical treatment for middle cerebral
      aneurysm (MCAA), and results and prognosis thereof. METHODS: The clinical data,
      including location, size, main presentations, and Hunt & Hess grade, of 55
      consecutive MCAA patients were prospectively analyzed. The surgical outcome was
      evaluated by Glasgow Outcome Scale (GOS). Follow-up was conducted for 23 (11-19)
      months. RESULTS: According to the Hunt & Hess classification, there were 9 cases
      in grade 0, 12 cases in grade I, 23 cases in grade II, 8 cases in grade III, 2
      cases in grade IV, and 1 case in grade V at admission. Headache (42 cases),
      vomiting (22 cases), and hemiplegia (11 cases) were the top 3 common
      presentations. Pterional craniotomy was adopted in all cases. Proximal to distal
      lateral fissure approach was used in 23 cases, distal to proximal approach in 27
      cases, and trans-hematoma approach in 5 cases. There were 45 cases treated by
      direct neck-clipping (clipping and resecting in 6 cases), 7 cases by parent
      artery reconstruction, and 3 cases by wrapping by muscle. The location of MCAA
      was at the bifurcation in 37 cases (37.2%), at proximal middle cerebral artery
      (MCA) in 13 cases (23.6%), and at distal MCA in 5 cases (9.1%). The largest
      diameter was 15.5 (3-70) mm. The main postoperative complications included
      hemiplegia (12 cases), aphasia (3 cases), and seizure (2 cases). Follow-up showed
      good recovery in 45 cases, moderate disability in 5, and severe disability in 5
      according to GOS. There was no vegetative state, death, and recurrence.
      CONCLUSION: With modern imaging techniques, perfect surgical plan, appropriate
      surgical approach, and careful microsurgical techniques, treatment of MCAA can be
      perfected and achieve satisfying outcome.

PMID- 19595098
TI  - [Embolization of aneurysm by chitosan-glycerophosphate-fibroblast tissue
      hydrogel, a tissue engineering material: experiment with rabbits].
AB  - OBJECTIVE: To evaluate the feasibility of the injectable thermosetting chitosan
      glycerophosphate-fibroblast (C-GP-FB) hydrogel as an embolizing material of
      intracranial aneurysm. METHODS: 2% chitosan solution and 56% glycerophosphate
      solution were mixed in different volume ratio to detect the pH, colloidization
      time at 37 degrees C, and mechanic strength. Fibroblasts were isolated from the
      skin of a rabbit and cultured with C-GP hydrogel of different ratios so as to
      determine the best ratio. Six rabbits underwent construction of aneurysm in the
      right brachiocephalic trunk. Three weeks later C-GP-FB hydrogel was infused into
      the aneurysm via microtube and balloon. X-ray photography was conducted soon to
      observe the embolizing effect. Three days, 1 week, and 4 weeks later tea rabbits
      were killed respectively with their aneurysms taken out to undergo HE staining
      and microscopy. RESULT: When the ratio of C/GP was 7:1 at pH 7.28, the
      colloidization time was (260+/-18) sec, and the mechanic strength reached 14 kPa.
      The C/GP volume ratio of 7:1 was regarded as the best ratio. When the fibroblasts
      were cultured with the C-GP hydrogel with the C/GP volume ratio of 7:1 the
      survival rate of the fibroblasts reached the peak of (89+/-2.74)%. X-ray
      photography showed that image of aneurysm failed to be spotted immediately after
      the infusion of the C-GP hydrogel. HE staining and microscopy showed that C-GP-FB
      gel had fine visualization under X-ray. Histological section (HE stain) showed
      that 3 days after the infusion the aneurysms was embolized by the C-GP-FB
      hydrogel and no obvious inflammatory cell was seen in the arterial wall; the
      first week there were many cells in the gel, the boundary between the C-GP-FB gel
      and vessel wall was clear, and the endotheliocytes were complete; and in the
      fourth week, the boundary between the gel and vessel wall was obscure, slight
      degradation could be observed in the edge of hydrogel, and immunofluorescence
      showed that there were many labeled cell in the gel. CONCLUSION: In the short
      term view, C-GP-FB hydrogel can be used to embolize aneurysms, at least with an
      obvious short-term effect.

PMID- 19595099
TI  - [Relationship between characteristic geometry and risk of rupture in cerebral
      saccular aneurysm].
AB  - OBJECTIVE: To explore the relationship between the characteristic geometry and
      the risk of rupture in cerebral saccular aneurysm. METHODS: The clinical features
      of 473 cerebral saccular aneurysm patients with complete materials of cerebral
      angiography, 426 with ruptured aneurysm and 47 with unruptured aneurysm, were
      analyzed retrospectively. The relation of depth, neck width, and aspect ratio
      (AR) of aneurysms to the risk of rupture were analyzed. RESULTS: The mean depth,
      neck width, and the AR of the patients with ruptured aneurysm were (5.9+/-3.0)
      mm, (3.0+/-1.2) mm, and (2.1+/-0.9), all significantly lower than those of the
      unruptured aneurysm patients [(8.0+/-4.2) mm, (4.8+/-2.4) mm, and (1.7+/-0.6)
      respectively, all P<0.01]. CONCLUSION: AR is not correlated with the location of
      aneurysms, but reflects the geometrical and hemodynamic features of cerebral
      saccular aneurysms very well. High AR may be useful in predicting imminent
      aneurysmal rupture. But by now, no definitive AR level is accepted in
      discriminating between unruptured and ruptured aneurysms.

PMID- 19595100
TI  - [Clinical applications of computer-assisted navigation technique in spinal
      pedicle screw internal fixation].
AB  - OBJECTIVE: To assess the value of computer navigation technique in spinal pedicle
      screw insertion. METHODS: 95 patients undergoing spinal pedicle screw internal
      fixation were randomly divided in 2 groups:navigation group (n=36) undergoing
      pedicle screw insertion with computer-assisted navigation technique, and
      conventional group (n=50) undergoing pedicle screw insertion using conventional
      anatomic landmark combined. The 2 groups were compared in respect to screw canal
      preparation time, accuracy of screw position, and incidence of postoperative
      complication. RESULTS: 206 screws were inserted in the navigation group, 169
      being with excellent outcome (82.0%), 29 with good outcome (14.1%), and 8 with
      bad outcome (3.9%). Nine patients in the navigation group failed to adopt the
      computer-assisted navigation technique because of different reasons. 285 screws
      were inserted in the conventional group, 257 being were excellent outcome
      (90.2%), 28 with good outcome (9.8%), and none with bad outcome. The general
      fitness rate of the navigation group was 96.1%, not significantly different from
      that of the conventional group (100%, P>0.05). The screw canal preparation time
      of the navigation group was (360+/-22) sec, significantly longer than that of the
      conventional group [(56+/-8) sec, P<0.001)]. No postoperative complication was
      found in both groups. CONCLUSION: The accuracy of pedicle screw insertion using
      preoperative CT-based navigation technique is not different from that using
      conventional anatomic landmark, but the operation time is significantly
      prolonged. Preoperative CT-based navigation technique has limited value in spinal
      pedicle screw insertion.

PMID- 19595101
TI  - [Application of posterior short-segment fixation combined with intermediate
      screws in fresh thoracolumbar compressed fracture: short-term outcomes in 27
      cases].
AB  - OBJECTIVE: To observe the short-term outcomes of the application of posterior
      short-segment fixation combined with intermediate screws in fresh thoracolumbar
      fracture. METHODS: Posterior short-segment fixation combined with intermediate
      screws was used in 27 patients suffering from fresh thoracolumbar fracture, 19
      males and 8 females, aged 45 (22-71). X-ray photography was conducted before and
      after operation. RESULTS: The height of fractured vertebra was 57.6%+/-16.5% of
      the normal value before operation, and was restored to 93.8%+/-11.9% after
      operation; the segmental kyphosis angle on the sagittal plane was 20.8+/-9.4
      degrees before operation, and decreased to 5.9+/-7.4 degrees after operation
      (both P<0.001). CONCLUSION: Using pedicle screws on the fractured vertebra via
      posterior approach conditionally helps reduce the fractured vertebra and correct
      the kyphosis, and enhance the stiffness of the internal fixation system as well.

PMID- 19595102
TI  - [Analysis of drug-induced acute renal failure in Shanghai].
AB  - OBJECTIVE: To investigate the incidence and prognosis of drug-induced acute renal
      failure (ARF) in Shanghai. METHODS: The registration forms of ARF patients
      admitted in 17 hospitals of and over the middle class in Shanghai from January 1,
      2004 to December 31, 2006 were screened prospectively. The data, such as
      epidemiology, survival, mortality, and morbidity were analyzed. RESULTS: 347 of
      the 1200 ARF patients (28.9%), 224 males and 123 females, aged (58+/-20),
      suffered from drug-induced ARF. 51.0% of the 347 patients were older than 60.
      60.2% of the drug-induced ARF in the non-surgical departments were community
      acquired, while 55.7% of the drug-induced ARF in the surgical departments were
      hospital-acquired. Among the non-surgical departments, the incidence of hospital
      acquired drug-induced ARF was the lowest in the department of nephrology (9.5%),
      while higher in the departments of hematology, cardiology, and neurology, and
      among the surgical departments, it was the lowest in department of renal surgery,
      while higher in the departments of liver transplantation, neurosurgery, and
      cardiovascular surgery. The most common complication was chronic kidney disease
      (CKD) (n=69, 19.9%), followed by cerebrovascular disease (n=59, 17.0%), diabetes
      mellitus (n=43, 12.4%), and hypertension (n=41, 11.8%). Renal biopsy showed acute
      tubular necrosis (18, 37.5%), acute interstitial nephritis (11, 22.9%), and acute
      infectious tubulo-interstitial nephritis (6, 12.5%). Antibiotics (47.8%) were the
      head causes of drug-induced ARF, especially aminoglycoside (17.0%) and
      cephalosporins (12.7%), followed by diuretics (22.2%) and radiocontrasts (13.3%).
      22.5% of the drug-induced ARF patients had used two or more drugs. 119 patients
      (34.3%) needed renal replacement treatment. 100 of the 347 patients (28.8%) died.
      188 of the surviving patients (54.2%) had their renal function recovered
      completely, the renal function of 42 of them (12.1%) was recovered partially, and
      17 of then (4.9%) required dialysis when discharged. CONCLUSION: Drug-induced ARF
      is common with higher incidence in the patients with complications. Antibiotics,
      diuretic agents, and contrast medium are the main causes.

PMID- 19595103
TI  - [Long-term outcomes of percutaneous lumbar discectomy and microendoscopic
      discectomy for lumbar disc herniation].
AB  - OBJECTIVE: To evaluate the long-term effects of percutaneous lumbar discectomy
      (PLD) and microendoscopic discectomy (MED) in treatment of lumbar disc
      herniation. METHODS: A questionnaire survey by letter and telephone was conducted
      among 104 patients undergoing PLD and 82 patients undergoing MED during January
      2000 to March 2002, to investigate the Oswestry disability index (ODI), Short
      Form-36 (SF-36) score, and Japanese Orthopedic Association (JOA) score. RESULTS:
      The excellent/good rate (ODI score=0-20%) of the MED group was 79.27%,
      significantly higher than that of the PLD group (71.15%, P=0.0397). However,
      longer The hospitalization duration of the MED group was 11, 6 d, significantly
      longer than that of the PLD group (7.9 d, P<0.01), and the mean cost of the MED
      group was, significantly higher than that of the PLD group (P<0.01). Long-term
      complications were observed in 3 patients of the MED group (3.49%) while none in
      the PLD group. CONCLUSION: Both PLD and MED are minimally-invasive-technique with
      a long-term efficacy and safety on lumbar disc herniation. Although the long-term
      outcome of the MED group is better than PLD, the complication rate,
      hospitalization duration, and cost of the MED group are higher.

PMID- 19595104
TI  - [Clinical effect of transcatheter arterial chemoembolization combined with high
      intensity focused ultrasound ablation in treatment of large hepatocellular
      carcinoma].
AB  - OBJECTIVE: To investigate the clinical effect of transcatheter arterial
      chemoembolization (TACE) combined with high intensity focused ultrasound (HIFU)
      ablation in treatment of large hepatocellular carcinoma (HCC). METHODS: Sixty
      eight patients with unresectable HCC were randomized into 2 age, tumor size, TNM
      stages, and liver function grade-matched groups: TACE group (n=30) undergoing
      TACE and TACE+HIFU group (n=38) undergoing 2-3 weeks after TACE. A total of 88
      tumors (9.3+/-3.2) (5.0-14.5) cm in diameter were detected, and the largest tumor
      in a specific patients with multiple lesions was selected for observation. Follow
      up was conducted for (13+/-7) (3-24) months to observe the necrosis of tumor,
      size of tumor, local recurrence, and survival of patient. RESULTS: The clinical
      symptom remission rate was 90.6% (29/32) in the TACE+HIFU group and 70.8% (28/38)
      in the TACE group. The tumor necrosis and minification rates of the TACE+HIFU and
      TACE groups were 73.7% and 68.4% respectively, both significantly higher than
      those of TACE group (26.7% and 33.3% respectively, both P<0.01). The tumor local
      recurrence rate of the TACE+HIFU group was 21.1%, not significantly different
      from that of the TACE group (33.3%, P>0.05). The median survival duration of the
      TACE+HIFU group was 18 months, significantly longer than that of the TACE group
      (10 months, P<0.05). CONCLUSION: Compared with the TACE therapy alone, the
      combination therapy improves the tumor necrosis rate and prolongs the patients'
      survival duration.

PMID- 19595105
TI  - [Incidence and influential factors of post-operative nausea and vomiting
      following gynecological surgery: analysis of 492 cases].
AB  - OBJECTIVE: To investigate the incidence and influential factors of post-operative
      nausea and vomiting (PONV) following gynecologic surgery so as to provide
      guideline effective for clinical management. METHODS: The clinical data of 492
      qualified consecutive female patients who had undergone gynecological surgery
      were analyzed. Univariate analysis and multivariate logistic regression were
      applied to examine the relations between the perioperative variables and
      occurrence of PONV within 6 h or 24 h following gynecologic procedures. RESULTS:
      PONV developed in 218 patients within 24 h following surgery (44.3%) while in 161
      patients within 6 h following surgery (32.7%). Multivariate logistic regression
      analysis identified PONV history and perioperative opioids administration as
      significant predictors of PONV within 24 h following gynecologic surgery, while
      PONV history, general anesthesia, and postoperative shivering predictors of PONV
      within 6 h after surgery, and found the administration of dexamethasone or
      droperidol as consistent protective factors of PONV within 6 h or 24 h following
      surgery. CONCLUSION: For gynecologic surgery, previous PONV history will increase
      the risk for PONV following current surgery. Perioperative opioids administration
      will intensify the risk for the development of PONV within 24 h following
      surgery, while general anesthesia and postoperative shivering for PONV within 6 h
      after surgery. Perioperative dexamethasone or droperidol will decrease the
      incidence of PONV within 6 h or 24 h following gynecologic procedures.

PMID- 19595106
TI  - [Diagnosis and treatment of aortic origin of the right pulmonary artery: analysis
      of 14 cases].
AB  - OBJECTIVE: To investigate the diagnosis of aortic origin of the right pulmonary
      artery (AORPA) and evaluate the efficacy of surgical treatment therefore.
      METHODS: The clinical data of 14 AORPA patients, 9 male and 5 female, aged 4 (60
      days-23 years), hospitalized from May 1992 to March 2007, twelve of which were
      surgically treated through 5 different procedure, and two of which were denied
      surgical procedure due to Eisenmenger syndrome. Follow-up was conducted for
      (5.15+/-3.48) years. RESULTS: The diagnosis of 12 out of the 14 patients was
      confirmed before operation, and 2 of them were misdiagnosed by echocardiography.
      Two patients died during the peri-operational period due to low output syndrome
      or pulmonary hypertension crisis. One patient died from right cardiac failure 4
      yrs after the surgical procedure. Of the 9 surviving patients, 5 were in NYHA
      functional class I, and 4 in class II. CONCLUSION: In diagnosis of AORPA right
      ventriculography and aortic angiography or multi-sliced CT angiography or MRI are
      necessary to avoid misdiagnosis. The early and mid-long term effects of surgical
      treatment for AORPA are good, but it was imperative to adopt these procedures as
      early as possible to heighten the cure efficacy.

PMID- 19595107
TI  - [Experimental study of reservation flaval ligament on prevention of peridural
      adhesion after operation on lumbar disc].
AB  - OBJECTIVE: Through an experiment in rabbits, to evaluate the role of reservation
      flaval ligament using different methods to prevent the epidural adhesion by
      observing the morphological changes and provide experiment evidences for clinic.
      METHODS: 45 adult rabbits were divided into three groups: Group A (treated with
      no reservation of flaval ligament), Group B (treated with reserving half flaval
      ligament), and Group C (treated with reserving the complete flaval ligament).
      Every group has 15 rabbits. At the 2nd, 4th and 8th weeks, the samples were
      obtained for gross observation, histological examinations, and the images were
      analysed by computer. The data were processed using SPSS11.5. RESULT: Gross
      Observation and Histological Examinations, at the 2nd, 4th and 8th postoperative
      week, there was significant difference between the group A, B and C (gross
      observation: F2w=4.660, F4w=8.591, F8w=31.858, P<0.05; histological examinations:
      F2w=5.190, F4w=9.561, F8w=34.658, P<0.05). Images analysis: the difference was
      very significant in the groups at 2nd, 4th and 8th weeks (F2w=30.783, F4w=47.350,
      F8w=25.544, P<0.01). With time passing, the ratio became larger and larger in the
      same group. CONCLUSIONS: Reserving the complete flaval ligament can significantly
      prevent the peridural adhesion from the back as a barrier, and can reduce the
      adhesion formed.

PMID- 19595108
TI  - [Intermittent low-dose administration of recombinant human parathyroid hormone (1
      34) promotes the expression of Runx2 during early stage of fracture healing].
AB  - OBJECTIVE: To study the correlation of intermittent low-dose administration of
      recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] and the expression of
      Runx2 during early stage of fracture healing. METHOD: Sixty 2-month old male
      Sprague-Dawley rats underwent close unilateral femoral fracture and
      intramedullary nail fixation, and then were randomly divided into 2 equal groups:
      treatment group undergoing subcutaneous injection of rhPTH (1-34) 10 microgxkg(
      1)xd(-1) immediately after the operation, and control group undergoing
      subcutaneous injection of normal saline of the same dose. Six rats from each
      group were killed with their bilateral femurs taken out on days 2, 4, 7, 14, and
      21 after the operation to undergo X-ray photography Tissue RNA and protein were
      extracted from the bone tissues and the levels of Runx2 mRNA and protein
      expression were evaluated through real time quantitative PCR and Western
      blotting. Blood samples were collected from the abdominal aorta before the rats
      were killed to undergo detection of serum calcium, phosphorus, and alkaline
      phosphatase (AKP). RESULTS: The Runx2 mRNA levels in the fractured femurs of the
      rhPTH (1-34) group on days 14 and 21 after the operation were 2.6 and 3.8 times
      as those of the control group respectively (both P<0.05). The Runx2 protein
      levels in the fractured femurs of the rhPTH (1-34) group on days 14 and 21 after
      the operation were significantly higher than those of the control group
      respectively too. Since day 14 fracture healing was seen, and the status of
      fracture healing was better in the rhPTH (1-34) group than in the control group
      on days 14 and 21. The levels of serum calcium ion on days 14 and 21 of the rhPTH
      (1-34) group were both significantly higher than those of the control group (both
      P<0.05). There were not significant differences in the serum levels of AKP,
      osteocalcin and collagen type Iat any time point between the 2 groups.
      CONCLUSION: Intermittent low-dose administration of rhPTH (1-34) up-regulates the
      levels of osteogenesis-specific Runx2 mRNA and protein expression to accelerate
      the early stage fracture healing during the early stage.

PMID- 19595109
TI  - [Restoration of segmental bone defect by calcium sulfate pellet: experiment with
      rabbit].
AB  - OBJECTIVE: To compare the effects of different calcium sulfate pellets made by
      different methods in treating segmental defect of bone. METHODS: Eighty New
      Zealand white rabbits underwent cutting off a segment in the middle part of
      radius so as to establish models of radial segmental defect, and than were
      divided into 4 groups: Group A as control group, Group B with calcium sulfate
      pellet made by routine method implanted into the defect, Group C with chitosan
      coated pressed calcium sulfate pellet implanted into the defect, and Group D with
      chitosan coated pressed calcium sulfate pellet combined with recombinant human
      bone morphogenetic protein (rhBMP)-2 implanted into the defect: X-ray photography
      was done every 4 weeks to observe the new bone formation. Four, 8, and 12 weeks 5
      rabbits from each group were killed. The defect segments with parts of normal
      bone at both ends were cut off to undergo fluorescence microscopy and biomechanic
      three point bending test. RESULTS: X-ray photography and histological examination
      showed that new bone formation of cortex and reconstruction of marrow cavity were
      seen in Groups D and C, especially in Group D. The new bone mineralization rate
      of Group D was significantly higher than that of Group C (P<0.05) which was
      significantly higher than that of Group B (P<0.01). The anti-bending strength
      ratio of Group D was (47.5%+/-2.1%, significantly higher than that of Group C
      [(39.6+/-1.7)%, F=125.3, P<0.01], and the anti-bending strength ratios of Groups
      D and C were both significantly higher than those of Groups B and A [(23.6+/
      3.3)% and (21.3+/-2.7)%]. CONCLUSION: Chitosan coated pressed calcium sulfate
      pellet shows relatively higher anti-bending strength and slightly slower
      resorption that closely coincide with the growth rate of new bone. It can be used
      to restore segmental bone defect, and particularly when combined with rhBMP-2.

PMID- 19595114
TI  - [Improving knowledge on resection operation for colorectal cancer liver
      metastasis].

PMID- 19595110
TI  - [Correlation between single nucleotide polymorphism of prothrombin gene G20210
      and deep vein thrombosis after total joint replacement].
AB  - OBJECTIVE: To evaluate the correlation between prothrombin gene G20210A mutation
      and deep vein thrombosis after total joint replacement through detecting
      distribution frequency of single nucleotide polymorphism of the gene in patients
      undergoing total joint replacement. METHOD: PCR and direct sequencing of DNA are
      used to analyze the frequency of prothrombin gene G20210A mutation in 55 patients
      undergoing total joint replacement, and the relationship between the mutation and
      deep vein thrombosis after total joint replacement is evaluated. RESULT:
      Morbidity of prothrombin gene G20210A mutation in 55 patients is 0, both in
      either DVT group (27 patients) or non-DVT group (28 patients). There is no
      significant difference between the two groups (P>0.05). CONCLUSION: Mutation of
      prothrombin gene G20210A in Chinese patients is rare, and there is no correlation
      between the genetic mutation and deep vein thrombosis after total joint
      replacement.

PMID- 19595115
TI  - [Nanoparticle-mediated endostatin gene therapy targeting hepatocellular carcinoma
      utilizing heat-inducible promoter].
AB  - OBJECTIVE: To investigate the inhibitory effect of nanoparticle-mediated
      endostatin gene therapy on hepatocellular carcinoma xenografts combined with
      local hyperthermia utilizing heat-inducible promoter. METHODS: Heat-inducible
      HSP70B promoter and fusion gene of Endo/EGFP were cloned into pcDNA3.1 (+)
      plasmid, thus obtaining recombinant plasmid of pcDNA3.1 (+)/HSP70-Endo/EGFP using
      restriction endonucleases BglII/HindIII and EcoRI/SalI. The nanoparticles
      polylactide-grafted dextran copolymer (DEX-g-PLA) encapsulating the recombinant
      plasmid DNA were prepared by the method of emulsification and evaporation of
      organic solvent, and the surface shape of nanoparticles was observed by
      transmission electron microscope. Human hepatocellular cells of the lines HepG2
      and ECV304 were cultured and transfected with the recombinant plasmid utilizing
      the nanoparticles. Following thermal induction at 37 degrees C, 39 degrees C, 41
      degrees C, 43 degrees C, and 45 degrees C for 30 min, the expression of enhanced
      green fluorescent protein (EGFP) was detected by fluorescence microscope and flow
      cytometry. The concentration of endostatin protein in the supernatant was tested
      by ELISA, and the growth inhibition on the HepG2 and ECV304 cells was tested by
      MTT method. Balb/c nude mice were inoculated with HeG2 cells and then randomly
      divided into 2 groups to undergo intra-tumor injection of nanoparticles (heated
      or not heated), Lipofectamine 2000. Mice were used as controls without intra
      tumor injection. Four weeks the mice were killed to observe the tumor inhibition
      rate. RESULTS: The nanoparticles encapsulating recombinant plasmid were of round
      or elliptical shape 90 approximately 120 nm in diameter. The efficiency of gene
      transfection mediated by nanoparticles was about 30.65%. The expression of
      Endo/EGFP gene in the HepG2 cells was up-regulated along with the increase of
      temperature, peaked at 43 degrees C (with the EGFP expression level 3.3 times as
      that at 37 degrees C). The concentration of endostatin protein in the supernatant
      of the 43 degrees C group was (177 +/- 28) microg/L, significantly higher than
      that of the 37 degrees C group [(41 +/- 10) microg/L]. MTT results indicated that
      endostatin inhibited the growth of ECV304 cells with a inhibition rate of 96.3%
      at the time point of 72 h in the 43 degrees C group, however, it did not show
      influence on HepG2 cells no matter what was the temperature The tumor inhibition
      rate in the mice of endostatin with thermal induction group was 58.5%,
      significantly higher than that of the 37 degrees C group (34.9%, P < 0.05).
      CONCLUSION: Low temperature thermal induction enhances the expression and
      secretion of endostatin in hepatocellular cells transfected by nanoparticles, and
      inhibits the growth of hepatocellular carcinoma xenografts.

PMID- 19595116
TI  - [Nanogold inhibits angiogenesis and growth of liver cancer: experiment with
      mice].
AB  - OBJECTIVE: To investigate the effects of nanogold in inhibition of angiogenesis
      and growth of liver cancer cells. METHODS: Nanogold was co-incubated with VEGF165
      and VDGF121 respectively. Atomic force microscopy (AFM) was used to observe the
      changes of the form of the particles. Human umbilical vascular endothelial cells
      (HUVEC) were serum-starved for 24 hours, then co-cultured with VEGF165 + nanogold
      or VEGF121 + nanogold for 24 h. ATM was used to observe the ultrastructure of the
      cells. Another HUVEC were serum-starved for 24 hours and then cultured with
      VEGF165 (10 microg/L) 100 microl + nanogold 125, 250, and 500 nmol/L 100 microl
      respectively for 5 min. Then Western blotting was used to detect the
      phosphorylation protein of phospholipase C (PLC)-gamma1 on VEGFR-2.
      Hepatocellular cancer cells of the line H22 were injected subcutaneously into the
      right armpit of 20 Balb/c nude mice. When the size of transplanted tumor reached
      about 8 mm, the mice were divided into 2 equal groups: experimental group
      undergoing injection of nanogold into the tumor once a day for 8 days, and
      control group injected with normal saline. On day 14 the mice were sacrificed
      with the liver tumors taken out to measure the size and weight. The microvascular
      density (MVD) of tumor was determined by immunohistochemical staining. RESULTS:
      ATM showed that acted with VEGF165, the size of nanogold became over 30 nm.
      Treated with VEGF165 the HUVEC became larger with obvious pseudopodium. However,
      such changes were obviously milder in those HUVEC treated with nanogold +
      VEGF165. The PLC-gamma1 phosphorylation level VEGF receptor-2 was decreased along
      with the increase of the concentration of nanogold. The MVD of liver cancer
      tissue in the experimental group was 14.27 +/- 1.08, significantly lower than
      that of the control group [(23.52 +/- 1.36), P < 0.01]. The mean weight and
      volume of tumor of the experimental group were (1.39 +/- 0.08) g and (1.37 +/-
      0.34) cm(3) respectively, both significantly lower than those of the control
      group [(2.47 +/- 0.15) g and (2.49 +/- 0.78) cm(3) respectively, both P < 0.05]
      with a tumor growth inhibition rate of 43.72%. CONCLUSION: Nanogold significantly
      inhibits the angiogenesis and growth of liver cancer cells with the possible
      mechanism that nanogold inhibits the VEGF165-induced signaling.

PMID- 19595117
TI  - [Meta-analysis of the efficacy of transcatheter arterial chemoembolization
      combined with percutaneous ethanol injection in treating unresectable primary
      liver cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial
      chemoembolization combined with percutaneous ethanol injection in treating
      unresectable primary liver cancer. METHODS: MEDLINE (1966-June 2008), EMBASE
      (1974-June 2008), the Cochrane Library (Issue 2, 2008), CBMdisc (1978-June 2008),
      CNKI (1979-June 2008), and Wanfang Database were searched without language
      limitation. All randomized controlled trials comparing transcatheter arterial
      chemoembolization alone with transcatheter arterial chemoembolization combined
      with percutaneous ethanol injection for treating unresectable primary liver
      cancer were identified and screened by two reviewers, and the methodological
      quality of the included randomized controlled trials were evaluated by Jadad
      scale. The Cochrane Collaboration's RevMan4.2 software was used for the analysis
      of the data extracted from the included randomized controlled trials. RESULTS:
      Fourteen randomized controlled trials involving 857 patients were included with
      12 trials published in Chinese and 2 in English. Meta-analysis of the data
      extracted from the included randomized controlled trials showed that
      transcatheter arterial chemoembolization combined with percutaneous ethanol
      injection could significantly improve the overall survival rates compared with
      transcatheter arterial chemoembolization alone, with the corresponding relative
      risk (RR) values (95% CI) for the 1, 2, and 3-year survival of 1.37 (1.21 -
      1.56), 1.74 (1.49 - 2.04), and 2.26 (1.70 - 3.02) respectively; and the RR alpha
      feto-protein (AFP) negative conversion rate, AFP lowering rate, and tumor focus
      efficacy rate were 1.39 (1.24 - 1.56), 1.69 (1.38 - 2.07), and 1.56 (1.38 - 1.77)
      respectively. Side effects or adverse events related with transcatheter arterial
      chemoembolization were reported in 11 randomized controlled trials, mainly liver
      function impairment, fever, gastrointestinal symptom, and transient pain, and no
      major treatment-related complication or death was reported. CONCLUSION: Compared
      with transcatheter arterial chemoembolization alone, transcatheter arterial
      chemoembolization combined with percutaneous ethanol injection significantly is a
      better approach in treating unresectable primary liver cancer, increasing the
      overall survival rate, AFP negative and lowering rates, and tumor response rate.
      However, the methodological quality of most reported randomized controlled trials
      is low.

PMID- 19595118
TI  - [Preparation of doxorubicin encapsulated in amphiphilic polysaccharide
      nanoparticles and anti-hepatocarcinoma effect thereof].
AB  - OBJECTIVE: To investigate the sustained release rule of doxorubicin/polylactide
      grafted dextran copolymer (DOX/DEX-PLA) nanoparticles and the effect thereof in
      killing hepatocarcinoma cells. METHODS: DOX/DEX-PLA nanoparticles were prepared
      by method of emulsification & evaporation of organic solvent. Its morphology was
      observed by transmission electron microscopy and the encapsulating efficiency of
      DOX was determined by ultraviolet spectrophotometry. DOX/DEX-PLA was put in a
      dialysis bag to observe the releasing characteristics of DOX from DOX/DEX-PLA
      nanoparticles in vitro. Human liver carcinoma cells of the line HepG2 were
      cultured with DOX/DEX-PLA of different concentrations or the original drug of DOX
      as control group for 24, 36, or 48 h. MTT method was used to observe the cancer
      inhibition rate. BALB/c nude mice underwent subcutaneous injection of HepG2 cells
      at the right scapula and then randomly divided into 4 groups to undergo
      intravenous injection of DOX/DEX-PLA (excremental group), original drug of DOX
      (naked drug group), DEX-PLA (nanovector group), or normal saline (blank control
      group) once every 5 days for 3 times. Twenty-one days later the mice were killed
      with the tumors taken out to measure the weight to analyze the inhibitory effect
      against hepatocarcinoma cells. RESULTS: The DOX/DEX-PLA nanoparticles were of
      round or elliptical shape with the diameter of about 83 nm, and the DOX
      entrapment efficiency was about 67.1%. The releasing test in vitro manifested a
      sustained release of over 50% of DOX encapsulated in DOX/DEX-PLA nanoparticles
      for about 7 days. Both the DOX/DEX-PLA nanoparticles and naked drug DOX inhibited
      the growth of HepG2 cells with a similar inhibitory rate (51.3% vs 50.7%, P >
      0.05), meanwhile the DEX-PLA nanovector failed to inhibit the HepG2 cells. In
      vivo experiment showed an inhibitory rate of DOX/DEX-PLA nanoparticles on
      hepatocellular carcinoma xenografts of 68.56%, significantly higher than that of
      the naked drug DOX (48.17%). CONCLUSION: DOX/DEX-PLA nanoparticles can
      effectively inhibit the growth of hepatocarcinoma cells.

PMID- 19595119
TI  - [Clinical analysis and study of immunological function in syphilis patients with
      seroresistance].
AB  - OBJECTIVE: To investigate the relevant factors of seroresistance of syphilis by
      clinical analysis and study of immunological function. METHODS: The clinical data
      of 172 patients with syphilis were analyzed to observe the correlation of
      seroresistance with the factors including original titer of rapid plasma regain
      (RPR), disease course, and medication. Flow cytometry was used to analyze the
      proportions of T-lymphocyte subset and NK cells in the peripheral blood of 40
      untreated syphilitic patients at various stages, 20 syphilitic patients whose
      serology turned negative after treatment, 20 serum resistance patients, and 18
      healthy controls. RESULTS: The seroresistance rate was 8.7% in the primary
      syphilis patients (2/23), significantly lower than that of the latent syphilis
      patients (42.2%, 38/90, P = 0.001). The seroresistance rate of the patients
      treated with benzathine penicillin was 26.4% (42/159), significantly lower that
      of the patients treated with macrolides (76.9%, 10/13, P = 0.000). The proportion
      of CD8(+) T cells of the untreated syphilitic patients was (30% +/- 8%),
      significantly higher than that of the normal controls [(24% +/- 4%), P < 0.01].
      The proportion of NK cells of the untreated syphilitic patients was (13% +/- 5%),
      significantly lower than that of the normal controls (16% +/- 6%, P < 0.05). The
      proportion of CD3(+) T cells of the patients whose serology turned negative after
      treatment was (71% +/- 7%), significantly higher than that of the normal controls
      (65% +/- 7%, P < 0.05). The proportion of CD8(+) T cells of the patients whose
      serology turned negative after treatment was (29% +/- 7%), significantly higher
      than that of the normal controls (24% +/- 4%, P < 0.01). There were not
      significant differences in the proportions of different cells among the patients
      with seroresistance, serological negative conversion, and normal controls.
      CONCLUSION: Syphilis patients with a high baseline RPR titer, a latent course and
      macrolide therapy are prone to be seroresistant. Whether the occurrence of serum
      resistance is related to the inhibition of cell-mediated immunity requires
      further exploration.

PMID- 19595120
TI  - [Analysis of CD4+CD25+Foxp3+ regulatory T cells in patients of haemorrhagic fever
      with renal syndrome].
AB  - OBJECTIVE: To investigate the percentage and significance of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells in the patients with haemorrhagic fever
      with renal syndrome (HFRS). METHODS: Peripheral blood samples were collected from
      27 HFRS patients, and 19 healthy controls to examine the proportion of the
      CD4(+)CD25(+)Foxp3(+) cells. RT-PCR was used to detect the Foxp3 mRNA expression
      in the mononuclear cells in peripheral blood. Biopsy was conducted on the HFRS
      patients during oliguria stage. Peripheral blood samples and morning urine
      samples were collected in the stages and in the very day of renal biopsy to
      examine the urine protein, urine creatinine (Cr), blood Cr, and creatinine
      clearance rate (Ccr). RESULTS: The percentages of CD4(+)CD25(+)Foxp3(+) in the
      HFRS patients in the hypotension, oliguria, polyuria, and convalescent stages
      were 5.0% +/- 1.2%, 3.1% +/- 0.8%, 4.2% +/- 0.9%, and 5.0% +/- 1.1% respectively,
      all significantly lower than that of the normal control group (6.5% +/- 2.1%, all
      P < 0.01). The proportion of CD4(+)CD25(+)Foxp3(+)T cells in the CD4(+)T cells in
      the oliguria stage was significantly lower than those in other stages and that of
      the normal controls (P < 0.01). The percentage of CD4(+)CD25(+)Foxp3(+) in the
      patients with HFRS was significantly correlated with the renal injury index (r =
      0.51, P < 0.01), but not significantly correlated with urine protein and renal
      function changes (r = 0.11 and 0.18, both P > 0.05). The expression level of
      Foxp3 mRNA in peripheral mononuclear cells of the HEFS patients in the oliguria
      stage was (503 +/- 64), significantly lower than that of the normal controls
      (3102 +/- 409, P < 0.01) and those of the HFRS patients in the hypotension,
      polyuria, and convalescent stages (1805 +/- 291, 1869 +/- 320, and 2697 +/- 420,
      all P < 0.01). CONCLUSION: The proportion of CD4(+)CD25(+)Foxp3(+) regulatory T
      cells decreases in patients with HFRS, which may contribute to the pathological
      process in such disease.

PMID- 19595121
TI  - [Prognostic analysis of middle and lower rectal cancer with different degrees of
      infiltration in mesorectum].
AB  - OBJECTIVE: To study the relationship between tumor infiltration in mesorectum and
      prognosis of middle and lower rectal cancer. METHODS: 49 patients with middle and
      lower rectal cancer underwent total mesorectal excision. Specimens were obtained
      during operation and underwent large slice pathologic technique to observe the
      degree of tumor infiltration in mesorectum and circumferential resection margin.
      Follow-up was conducted for 61 (9 - 66) months to observe the local recurrence
      rate, metastasis rate, and five-year survival rate. RESULTS: Follow-up showed a
      local recurrence rate of 12.2% (6/49), distant metastasis rate of 26.5% (13/49),
      and five-year survival rate of 67.3% (33/49). The rate of degree I of tumor
      infiltration in mesorectum was 40.8% (20/49), the degree II rate was 26.5%
      (13/49), and the degree III rate was 32.7% (16/49) with the corresponding local
      recurrence rates of 0, 7.7% (1/13), and 31.3% (5/16) respectively (chi(2) =
      7.357, P = 0.015), metastatic rates of 10% (2/20), 23.1% (3/13), and 50% (8/16)
      respectively (chi(2) = 7.405, P = 0.025), and the 5-year survival rates of 90%
      (18/20), 69.2% (9/13), and 37.5% (6/16) respectively. Kaplan-Meier survival
      analysis showed that the survival time was correlated with the degree of tumor
      infiltration in mesorectum (P = 0.012). The rate of circumferential resection
      margin involvement was 24.5% (12/49). In the 12 patients with positive
      circumferential resection margin, the local recurrence rate was 33.3% (4/12),
      whereas 5.4% (2/37) in those with negative circumferential resection margin
      (chi(2) = 6.577, P = 0.010). Distant metastasis rate was 50% (6/12) in the
      patients with positive circumferential resection margin, whereas 18.9% (7/37) in
      those with negative one (chi(2) = 4.491, P = 0.034). The 5-year survival rate of
      the patients with positive circumferential resection margin was 33.3% (4/12),
      significantly lower than that of the patients with negative circumferential
      resection margin [78.4% (29/37)]. Kaplan- Meier survival analysis showed survival
      time was correlated with the circumferential resection margin status (P = 0.009).
      CONCLUSION: The degree of tumor infiltration in mesorectum and circumferential
      resection margin status are important predictors of local and distant recurrence
      as well as survival of patients with middle and lower rectal carcinoma.

PMID- 19595122
TI  - [Detection of bacterial signal of 16S rRNA gene in prostate tissues obtained by
      perineal approach from patient with chronic pelvic pain syndrome].
AB  - OBJECTIVE: To explore the role of bacteria in etiology of chronic pelvic pain
      syndrome (CPPS), i.e., chronic prostatitis and the correlation between presence
      of bacterial signal of 16S ribosomal RNA (16S rRNA) gene and the response to
      antibiotics. METHODS: Samples of prostatic and subcutaneous tissues were obtained
      by biopsy via perineal approach from 112 CPPS patients, aged 20 - 48. Polymerase
      chain reaction was conducted to detect the 16S rRNA gene of bacteria. The
      patients were treated with gatifloxacin 0.4 g once a day for 4 weeks and then 4
      weeks later the effects of treatment were assessed by the National Institutes of
      Health Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: PCR was completed
      in 94 of the 112 patients, and 18 were excluded because their subcutaneous
      biopsies were positive for 16S rRNA, showing the possible contamination of their
      prostatic tissues. The total positive rate of bacterial 16S rRNA gene was 63.8%
      (60/94). The positive rate of bacterial 16S rRNA gene in the patients with IIIa
      CPPS and IIIb CPPS were 68.3% and 60.3% respectively. The total gatifloxacin
      effective rate of positive bacterial signal group after the was 55.0%,
      significantly higher than that of the negative bacterial signal group (14.7%, P <
      0.001). The gatifloxacin effective rate of the 16S rRNA positive IIIa CPPS
      patients was 75%, significantly higher than that of the 6S rRNA negative IIIa
      CPPS patients (23.1%, P < 0.001), and the gatifloxacin effective rate of the 16S
      rRNA positive IIIb CPPS patients was 37.5%, significantly higher than that of the
      6S rRNA negative IIIb CPPS patients (9.5%, P < 0.05). CONCLUSION: Bacterial
      infection is related to CPPS in part of the patients. Bacterial signal detection
      helps predict the effect of antimicrobial therapy.

PMID- 19595123
TI  - [Preparation and preliminary application of rabbit polyclonal antibodies against
      intracellular peptides of human platelet glycoprotein GPIbalpha].
AB  - OBJECTIVE: To prepare rabbit polyclonal antibodies against intracellular peptides
      of human platelet glycoprotein GPIbalpha. METHODS: Two peptides corresponding to
      human platelet GPIbalpha C-terminus were synthesized and purified by high
      performance liquid chromatography (HPLC). The peptides were cross-linked with
      keyhole limpet hemocyanin (KLH). Two New Zealand white rabbits were immunized
      with conjugated peptides for 3 times. The polyclonal antibodies were purified by
      Ammonium Sulfate Precipitation and identified by dot blotting and ELISA.
      GPIbalpha intracellular peptides phosphorylation was tested with these polyclonal
      antibodies by ELISA. RESULTS: The titers of the two polyclonal antibodies against
      the GPIbalpha C-terminus peptides were 1:32 000 and 1:64 000 respectively and
      both of these antibodies reacted with purified GPIbalpha. CONCLUSIONS: Two rabbit
      polyclonal antibodies against C-terminal peptides of human platelet GPIbalpha
      have been prepared successfully, providing a way for the preparation of these
      kinds of antibody. Both phosphorylation and dephosphorylation states exist in the
      intracellular peptide of human platelets.

PMID- 19595124
TI  - [Therapeutic effects of aerosolized signal transducer and activator of
      transcription 1 antisense oligonucleotide administered at different time points
      on bleomycin-induced pulmonary fibrosis: experiment with rats].
AB  - OBJECTIVE: To investigate the curative effects of inhaling signal transducer and
      activator of transcription 1 (STAT1) antisense oligonucleotide (ASON) on
      alveolitis and pulmonary fibrosis and the best administration time. METHODS:
      Twenty-five adult female Wistar rats were randomly divided into 5 equal groups:
      BLM group, undergoing intra-tracheal perfusion of BLM so as to establish animal
      models of alveolitis and pulmonary fibrosis and then inhaling aerosolized normal
      saline (NS); NS group undergoing intra-tracheal perfusion of NS and then inhaling
      aerosolized NS; ASON 0 d group, undergoing intra-tracheal perfusion of BLM and
      then inhaling aerosolized STAT1 ASON 3 ml immediately; ASON 7 d group, undergoing
      intra-tracheal perfusion of BLM and then inhaling STAT1 ASON 3 ml 7 days later;
      and ASON 14 d group undergoing intra-tracheal perfusion of BLM and then inhaling
      aerosolized STAT1 ASON 3 ml 14 days later. Aerosolized inhalation was repeated
      once every other day for 4 times. Twenty-eight days after intra-tracheal
      perfusion the rats were sacrificed with their lungs taken out to undergo
      pathological examination. NS was infused into the right lungs to get
      bronchoalveolar lavage fluid (BALF). ELISA was used to examine the concentrations
      of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha
      (TNF-alpha) in the BALF. RESULTS: The pathology result of the lung tissues showed
      that compared with the BLM and ASON 14 d groups, the alveolitis and pulmonary
      fibrosis of the ASON 0 d group were obviously milder. The scores of alveolitis
      and pulmonary fibrosis of the ASON 0 d group were (1.80 +/- 0.84) and (2.60 +/-
      0.55) respectively, both significantly lower than those of the BLM group [(2.40
      +/- 0.55) and (4.40 +/- 0.55) respectively] and those of the ASON 7 d group
      [(2.20 +/- 0.45) and (3.00 +/- 0.71) respectively] (all P < 0.05). The scores of
      pulmonary fibrosis of the ASON 7 d group was significantly lower than those of
      the BLM and ASON 14 d groups (both P < 0.05). The concentrations of TGF-beta and
      TNF-alpha in BALF of the ASON 0 d group were (48.11 +/- 3.46) pg/ml and (1.93 +/-
      0.14) ng/ml respectively, both significantly lower than those of the BLM group
      [(57.67 +/- 2.46) pg/ml and (2.45 +/- 0.25) ng/ml respectively, both P < 0.05].
      The concentration of TGF-beta in BALF of the ASON 0 d group was significantly
      lower than those of the ASON 7 d and ASON 14 d groups [(51.42 +/- 3.57) pg/ml and
      (55.8 3 +/- 1.79) pg/ml respectively, both P < 0.05]. The concentration of TGF
      beta in BALF of the ASON7 d group was significantly lower than those of the BLM
      and ASON 14 d groups (both P < 0.05). CONCLUSIONS: STAT1 ASON administered in the
      early stage helps depress the pulmonary fibrosis procedure, and the earlier the
      drug is administrated the better effect would be obtained. Aerosolized STAT1 ASON
      can be used as a therapeutic method for pulmonary fibrosis.

PMID- 19595125
TI  - [Isolation, purification, and functional evaluation of human pancreatic islet].
AB  - OBJECTIVE: To isolate and purify human islet according to the method established
      by Ricordi and to evaluate the function and safety of these isolated human
      islets. METHODS: Six pancreases were obtained from human corpses. The islets were
      isolated by liberase digestion and purificated by Ficoll density gradient
      centrifugation. The numbers, purity and vitality of the islets were analyzed. The
      various endocrine cell composition and distribution of the islets were checked by
      immunofluorescence staining. The glucose-induced insulin secretion was detected
      by chemiluminescence method. The isolated islets were transplanted under the left
      renal capsules of 10 streptozocin-induced diabetic nude mice. Twenty days later
      the left kidneys with transplanted islets of 2 mice with normal blood sugar were
      resected, and then blood sugar level was observed. An isolated human islet was
      suspended in RPMI-1066 culture medium for 72 h, then culture of pathogenic micro
      organisms, endotoxin and procoagulant activity were detected so as to evaluate
      the security of the islet products. RESULTS: The mean number of the isolated
      islets was (229 000 +/- 31 000) islet equivalents (IEQs)/pancreas or (4970 +/-
      1620) IEQs/g pancreatic tissue, the mean purity was (59.0 +/- 8.9)%, and the mean
      vitality was (89 +/- 3)% for the purified islets. Immunofluorescence staining
      showed that there were 4 types of endocrine cells normally distributed in the
      islets. The mean insulin stimulation index was 8.1 +/- 4.0 (3.8 - 10.2). The
      glycemia found in the diabetic nude mice decreased to normal levels from the
      third day after islet transplantation and maintained normal for over 30 days. The
      parameters of security in these islet products were under the standard scope.
      CONCLUSION: Human islets obtained according to Ricordi's method reach the
      standard for clinical islet transplantation in number, purity, vitality,
      function, and security.

PMID- 19595126
TI  - [Anti-tumor effect of eukaryotic expressing plasmid containing soluble tumor
      necrotic factor-related apoptosis inducing ligand combined with human angiostatin
      Kringle (1 - 3) genes on human gastric cancer xenografts in nude mice].
AB  - OBJECTIVE: To investigate the anti-tumor effect of eukaryotic expressing plasmid
      containing human angiostatin Kringle (1 - 3) [hAG (K1-3)] combined with soluble
      tumor necrotic factor-related apoptosis inducing ligand (sTRAIL) genes on human
      gastric cancer xenografts in nude mice. METHODS: Recombinant plasmids of pBud-hAG
      and pBud-hAG-TRAIL were constructed by subcloning technique. Twenty nude BALB/c
      mice were inoculated with human gastric cancer cells of the line BGC-823
      subcutaneously into the back. One week later after the appearance of implanted
      tumors the mice were randomly divided into 4 groups with pBud-hAG, pBud-hAG
      TRAIL, pBud blank plasmid, and normal saline (NS) injected into the tumors
      respectively once the other day for 7 times. The size of tumor was observed. 7
      days later the mice were killed with their tumors taken out. RT-PCR was used to
      detect the expression of hAG and sTRAIL. The microvessel density (MVD) of tumor
      was observed and recorded by detecting the protein of CD34 with
      immunohistochemistry on the microscopy. RESULTS: The MVD of tumor in the pBud-hAG
      TRAIL and pBud-hAG groups were (4.8 +/- 0.9)/HP and (4.6 +/- 1.2)/HP
      respectively, significantly lower than those of the pBud and NS groups [(17.4 +/-
      2.4)/HP and (18.2 +/- 2.7)/HP respectively, all P < 0.05], but there was no
      significant difference between the pBud-hAG-TRAIL and pBud-hAG groups. mRNA
      expression and protein expression of sTRAIL and hAG were positive in the pBud-hAG
      TRAIL and pBud-hAG groups. The tumor volumes of tumors of the pBud-hAG-TRAIL and
      pBud-hAG groups were (1.325 +/- 0.012) cm(3) and (1.862 +/- 0.017) cm(3)
      respectively, both significantly lower than those of the pBud and NS groups
      [(3.637 +/- 0.032) cm(3) and (3.521 +/- 0.028) cm(3) respectively, all P < 0.05].
      CONCLUSION: Angiostatin inhibits tumor angiogenesis through inhibiting the growth
      of vascular endothelial cells, and TRAIL induces tumor cell apoptosis. hAG (K1-3)
      combined with TRAIL can inhibit tumor growth more efficiently.

PMID- 19595127
TI  - [Ischemic postconditioning protects hypertrophic myocardium by ERK1/2 signaling
      pathway: experiment with mice].
AB  - OBJECTIVE: To investigate the effects of ischemic postconditioning (IPost) in
      protecting hypertrophic myocardium subjected to ischemic-reperfusion (I/R) and to
      study the role of extracellular regulated protein kinase (ERK1/2) in mediating
      such protection. METHODS: Transverse aortic constriction (TAC) operation was
      performed on 12-week-old C57/BL mice to establish left ventricular hypertrophy
      models. Sixty-four isolated TAC mouse hearts were mounted onto the Langendorff
      perfusion system and randomly divided into 4 equal group: (1) I/R group
      undergoing stable perfusion for 30 min, ischemia for 30 min, and re-perfusion for
      120 min (an I/R cycle) to cause hypertrophic myocardium I/R injury, (2) IPost
      group undergoing ischemia for 10s and reperfusion for 10s, totally 3 cycles (60s)
      before reperfusion for 120 min, (3) I/R+ PD98059 (an ERK1/2 inhibitor) group
      undergoing perfusion of Krebs-Henseleit (KH) buffer with PD98059 10(-5)mol/L for
      15 min and perfusion of KH buffer without PD98059 at the beginning of re
      perfusion, and (4) IPost + PD98059 group undergoing 3 cycles of IPost and
      perfusion of KH buffer with PD98059 10(-5)mol/L for 15 min at the beginning of re
      perfusion. Hemodynamic examination was conducted 120 min after re-perfusion to
      measure the left ventricular systolic pressure (LVSP), left ventricular end
      diastolic pressure (LVEDP), maximal uprising velocity of left ventricle pressure
      (dp/dt(max)), and minimal uprising velocity of left ventricle pressure
      (dp/dt(min)). After the I/R procedure the myocardium of the left ventricle was
      isolated to detect the infarction size (IS). Western blotting was used to detect
      the protein expression of extracellular signal-regulated kinase (ERK) 1/2,
      phosphorylated ERK1/2, Bcl-2, Bax, and mitochondrial and cytosolic cytochrome
      (Cyt). C. TUNEL was used to detect the apoptotic rate. RESULTS: The LVSP and
      dp/dt(max) levels of the IPost group were (85 +/- 4) mm Hg and (3811 +/- 230) mm
      Hg/s, both significantly higher than those of the I/R group [(68 +/- 5) mm Hg and
      (2830 +/- 230) mm Hg/s respectively, both P < 0.05]. Compared with the I/R group,
      the protein levels of phosphorylated ERK1/2, Bcl-2, mitochondrial CytC of the
      IPost group were all significantly higher, the protein levels of Bax and
      cytosolic CytC, and apoptosis index were significantly lower (all P < 0.05), and
      the IS was smaller (P < 0.05). I/R + PD98059 showed no effects on the above
      mentioned parameters. However, the results of the IPost + PD98059 group showed
      that in the first 15 min of reperfusion addition of PD98059 reversed all changes
      observed in the IPost group and eliminated the IPost protection by increasing IS
      to a level similar to that in the I/R group. CONCLUSION: IPost has protective
      effect in hypertrophic myocardium with I/R injury in vitro. ERK1/2 signaling
      pathway is involved in the protection of IPost by regulating the myocyte
      apoptosis.

PMID- 19595128
TI  - [The role of syntaxin1A/synaptosome-associated protein-25 in reversing
      hyperglycemia-induced alpha cell toxicity].
AB  - OBJECTIVE: To investigate the effects of reversal of hyperglycemic toxicity on
      the synthesis and secretion of glucagon by the alpha cells and the possible
      mechanisms thereof. METHODS: Mouse glucagonoma cells of the line TC1-6 were
      cultured in medium containing 5.5 mmol/L glucose for 10 days (low glucose group,
      LG), in medium containing 25 mmol/L glucose for 10 days (high glucose group, HG),
      in medium with 25 mmol/L glucose for 5 days and then in medium with 5.5 mmol/L
      glucose for 5 days (high-low glucose group, HL group), or in medium with 5.5
      mmol/L glucose for 5 days and then in medium with 25 mmol/L glucose for 5 days
      (LH group), Radioimmunoassay was used to detect the glucagon concentration in the
      supernatant. RT-PCR was used to detect the mRNA expression of glucagon in the TC1
      6 cells. Western blotting was used to detect the protein expression of the Snare
      proteins: syntaxin1A and synaptosome-associated protein (SNAP)-25. RESULTS: (1)
      The glucagon level of the HG/LG group was lower than that of the HG group by 29%
      (P < 0.05). (2) The glucagon mRNA expression level in the TC1-6 cells of the
      HG/HL group was significantly lower than that of the HG group by (52.6 +/- 2.8)%
      (P < 0.05). (3) The syntaxin1A and SNAP-25 expression levels in the TC1-6 cells
      of the HG group were significantly higher than those of the LG group by 36% and
      69% respectively (both P < 0.05), and the syntaxin1A and SNAP-25 expression
      levels in the TC1-6 cells of the HG/LG group were significantly lower than those
      of the HG group by 49% and 56% respectively (both P < 0.05). CONCLUSION: After
      removing the high glucose toxicity the abnormal glucagon secretion by the alpha
      cells can be ameliorated obviously, and the expression levels of syntaxin1A and
      SNAP-25 proteins that promote the secretion of glucagon are reduced accordingly.

PMID- 19595133
TI  - [New strategies for anti-scarring research].

PMID- 19595129
TI  - [Simvastatin prevents the development of pulmonary hypertension in the rats
      through reduction of inflammation].
AB  - OBJECTIVE: To investigate the protection of simvastatin on monocrotaline (MCT)
      induce pulmonary hypertension (PH) and the mechanism thereof. METHODS: Thirty-two
      male Sprague-Dawley rats were randomly divided into 4 equal groups: PH group
      undergoing subcutaneous injection of MCT and then gastric infusion of normal
      saline (NS) once a day for 21 days, simvastatin control group undergoing
      subcutaneous injection of NS and then gastric infusion of simvastatin 2 microg/g
      once a day for 21 days, simvastatin intervention group undergoing subcutaneous
      injection of MTS and then gastric infusion of simvastatin 2 microg/g once a day
      for 21 days, and control group undergoing subcutaneous injection and gastric
      infusion of NS. Three weeks later the mean pulmonary arterial pressure (mPAP) was
      detected by right heart catheter. Then the rats were killed with their lungs
      taken out. Arterial wall area/vessel area (W/V), and arterial wall
      thickness/vessel external diameter (T/D) were calculated. Perivascular
      inflammation was scored with the subjective scale of 0 (no) to 4 (severe).
      Pulmonary interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and
      monocyte chemotactic protein 1 (MCP-1) were tested by ELISA. RESULTS: The mPAP of
      the simvastatin intervention group was (23 +/- 7) mm Hg, significantly lower than
      that of the PH group [(34 +/- 9) mm Hg, P < 0.05], but not significantly
      different from that of the normal control group [(20 +/- 4) mm Hg, P > 0.05]. The
      W/V and T/D of the simvastatin intervention group were 0.442 +/- 0.061 and 0.325
      +/- 0.045 respectively, significantly lower than those of the PH group (0.560 +/-
      0.086 and 0.368 +/- 0.055 respectively, P < 0.01 and P < 0.05). The perivascular
      inflammation score of the simvastatin intervention group was (2.19 +/- 0.81),
      significantly lower than that of the PH group (3.40 +/- 0.65, P < 0.05), and the
      IL-6, TNF-alpha, and MCP-1 levels of the simvastatin intervention group [(264 +/-
      127), (179 +/- 91), and (697 +/- 211) pg/ml respectively] were all significantly
      lower than those of the PH group [(765 +/- 179), (447 +/- 86), (4428 +/- 757)
      pg/ml respectively, all P < 0.01]. CONCLUSION: The protective effects of
      simvastatin against MCT-induced PH may be associated with the inhibition of the
      perivascular inflammation and lung IL-6, TNF-alpha, and MCP-1 levels.

PMID- 19595134
TI  - [Tumor source theory of keloid occurrence].

PMID- 19595135
TI  - [Blocking of Notch signaling decreased scar formation in rabbit ear hypertrophic
      scar model].
AB  - OBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear
      model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears
      was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl
      L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated
      intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation
      of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group
      were treated with normal saline at the same time points. Experimental and control
      wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined
      histologically to quantify hypertrophic index and fibroblasts. The expression of
      epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin
      and Notch downstream molecules-P21, P63 were examined and analyzed with
      immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32,
      1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30
      +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were
      significantly reduced on days 21, 28 and 35, compared with the control group
      [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/-
      1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63
      increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/-
      4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/-
      4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin
      and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%,
      11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%,
      both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar
      epidermis to over-differentiation, and thereby inhibit proliferation of
      hypertrophic scars in the rabbit ears.

PMID- 19595136
TI  - [Function of STAT1 in proliferation and differentiation of human hypertrophic
      scar fibroblast induced by connective tissue growth factor].
AB  - OBJECTIVE: To validate whether STAT1 participated in the process of CTGF-induced
      proliferation and differentiation of human hypertrophic scar fibroblast (hHSF) on
      account of past research. METHODS: To cultivate hHSF with 6 patients'
      hypertrophic scar specimens together. Electrophoretic mobility shift assay (EMSA)
      was used to verify binding ability between DNA and STAT1 with the stimulus of
      different concentration CTGF (0, 5, 7.5, 10, 15 ng/ml) at 45th min and the
      stimulus of 10 ng/ml CTGF at different phase point (0, 10, 20, 30, 45, 60, 90,
      and 120 min). We divided cells into CTGF group, STAT1 ASODN group. STAT1 ASODN +
      CTGF group. control group. And MTT was used to detect the proliferation of hHSF
      on days1, 2 and 3, and RT-PCR to detect alpha-smooth muscle actin mRNA to follow
      the differentiation. RESULTS: EMSA showed that the binding ability between STAT1
      and DNA depended on the concentration of CTGF and peaked with the stimulation of
      10ng/ml CTGF. And at the same time, it peaked at 45 - 60 min with 10 ng/ml CTGF.
      MTT showed that cell proliferation of CTGF group was much higher than that of
      control group (all P < 0.05). And those of STAT1 ASODN group and STAT1 ASODN +
      CTGF group were much lower than those of control group and CTGF group (all P <
      0.05). RT-PCR showed that differentiation activation from fibroblast to
      myofibroblast of CTGF group, STAT1 ASODN group, STAT1 ASODN + CTGF group and
      control group were 0.78 +/- 0.08, 0.38 +/- 0.09, 0.76 +/- 0.10, and 0.40 +/-
      0.12, respectively. Differentiation activation of STAT1 ASODN group and control
      group were much lower than those of CTGF group and STAT1 ASODN + CTGF group (all
      P < 0.05). CONCLUSION: STAT1 ASODN is important in the process of proliferation
      of hHSF and it blocks the stimulation of CTGF on hHSF proliferation. The above
      result revealed that STAT1 participates in the process of hHSF proliferation
      induced by connective tissue growth factor.

PMID- 19595137
TI  - [Plastic surgical management of large cicatricial scalp alopecia].
AB  - OBJECTIVE: To investigate the proper ways to manage a large cicatricial scalp
      alopecia. METHODS: Based on the location, size and condition of the scarring
      lesions, 218 patients with 20 - 75% scarring alopecia were selected and treated
      with either dense-packing hair grafting technique (136 cases) or tissue expansion
      (82 cases). There were 209 in burn, 5 in avulsed injury and 4 in tumor excision.
      The lesions with thick, stable scars in the frontal or/and temporal areas
      undergoing either hair grafting or tissue expansion process as desired by the
      patients. In addition, the alopecia in an unstable scar on the skull, with skull
      defect under the lesion and the lesion involved in the back of the head was only
      treated with tissue expansion. The hair-grafting technique was carried out by
      harvesting a scalp strip from the back of the head, then dividing it into a
      series of 1 - 3 hair grafts and finally implanting them into the prepared
      recipient holes of the lesion with a desired hair direction. Ten areas with 1
      cm(2) size in 10 patients were randomly selected to examine the hair survival
      over 8 months post-operation. Tissue expansion was performed by firstly
      positioning a tissue expander in the subgaleal pocket of the scalp and serially
      inflating it with normal saline in 5 - 7 days intervals for about 3 months.
      Thereafter, an expanded scalp flap was designed, with the combination of
      advancement and rotation flap transplantation principles, to be transferred to
      the recipient site after lesion removal. RESULTS: In patients with hair-grafting
      technique, hair density reaching 60 - 80 hairs/cm(2) per session. Over 8-months
      following-up, the grafted hairs grew good with 98% hair survival. Forty-five
      patients with 20% - 30% scalp hair loss were reaching very satisfactory results
      with only one session while 91 patients with 31% - 50% hair loss were needed a
      second session to improve their appearance. In those with tissue expansion, 56
      patients with 20% - 50% scalp loss were managed in one session and 26 patients
      with 51% - 75% scalp loss needed secondary tissue expansion. All of the expanded
      hair-bearing flaps survived well with only minimal complications (9.8%) of the
      infective dome explosion in 3, slight skull depression in 2, seroma in 5 and
      early infection in 1. CONCLUSION: Either hair grafting or tissue expansion is
      proven as a safe and effective technique for restoration of large cicatricial
      scalp alopecia. The former technique could be of benefits to simple, mini
      surgical procedure, natural hair growth and good for lesion size under 30%. And
      the letter technique shows wider clinical indications, especially for the
      patients with unstable scar, skull defect under lesion and lesion over 50%. But
      the obvious drawbacks are multi-clinic visiting, disfigurement and long-term
      procedures.

PMID- 19595140
TI  - [Correlation between expressions of matrix metalloproteinase-2 & 9 and
      vasculogenic mimicry in gastrointestinal stromal tumors].
AB  - OBJECTIVE: To study the correlation between the expression of matrix
      metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF) and
      vasculogenic mimicry (VM) in gastrointestinal stromal tumors (GIST). METHODS: The
      immunohistochemical staining indices (SI) of MMP-2, MMP-9, VEGF were assessed on
      specimens of 84 human cases with GIST (21 VM-positive cases). Gelatin zymography
      analysis of the activity of MMP-2 and MMP-9 activities were performed on another
      42 human cases of GIST with fresh tissue (22 VM-positive cases). RESULTS: The
      staining indices (SI) of MMP-2 and MMP-9 were higher in the VM-positive group
      (4.10 +/- 2.05 and 3.43 +/- 1.89 respectively) than in the VM-negative group
      (2.98 +/- 1.97 and 2.38 +/- 1.84 respectively, both P < 0.05); there was no
      statistic difference in the SI of VEGF between VM-positive and VM-negative group.
      Gelatin zymography analysis showed that the activity of MMP-2 and MMP-9 were
      significantly higher in the VM-positive group (3.62 +/- 3.95 and 4.77 +/- 5.29
      respectively) than in the VM-negative group (1.26 +/- 1.21 and 2.11 +/- 1.54
      respectively, both P < 0.05). CONCLUSION: The expression of MMP-2 and MMP-9
      correlates with VM formation in GIST.

PMID- 19595138
TI  - [Clinical study of auricular keloid treatment with both surgical excision and
      intralesional injection of low-dose 5-fluorouracil and corticosteroids].
AB  - OBJECTIVE: To investigate whether intralesional injection of low-dose 5
      fluorouracil (5-Fu) and corticosteroid can increase effective rate and decrease
      recurrence rate of surgically removed auricular keloid. METHODS: Eighty-three
      patients with 166 total ear keloids were studied, including 79 keloids of helix
      and 87 of earlobe with an average disease history of 2.9 years. Ear piercing
      accounted for 92.7% for etiology. Keloids were first surgically removed in order
      to keep the normal auricular shape. Then intralesional injection of low-dose of 5
      Fu and corticosteroid was given 3 - 4 weeks after surgery and every 4 weeks
      afterwards. If no recurrence, the injection was given every 2 to 3 months with
      gradually tapered dose. The evaluation standard includes: patients with no
      recurrence 6 months after stopping drug injection and maintaining of the normal
      auricular shape are considered as "cure"; those remain having minor auricular
      deformity 6 months post-surgery with no recurrence and needing further treatment
      are considered as "effective". RESULTS: The treatment time period for 83 patients
      was 2 - 26 months (mean: 7 months). The patients were followed up for 0 - 49
      months (mean: 9 months) after withdrawing drug injection. There were 39 cured
      cases (47.0%) and 44 effective cases (53%). The total effective rate was 100%.
      Normal auricular shapes were achieved in 77 cases (92.7%) . CONCLUSION: Surgical
      removal of auricular keloid followed by intralesional injection of low-dose 5-Fu
      and steroid is an effective method to treat auricular keloid and prevent its
      relapse.

PMID- 19595142
TI  - [Expression and regulation of megalin in gallbladder mucosa associated with
      cholesterol gallstone disease].
AB  - OBJECTIVE: To explore the relationship between expression and regulation of
      Megalin in gallbladder mucosa and cholesterol gallstone disease. METHODS:
      Gallbladder mucosa, gallbladder wall, bile, gallstone were collected from 29
      patients with cholesterol gallstone disease (GS) and 12 patients with gallstone
      free (GSF). Lipids of bile and stone were measured by kits. Expression of Megalin
      and Cubilin was analyzed by Real-time PCR. GBC-SD cell line were treated with
      T0901317, 9-cis retinoic acid, chenodeoxycholic acid (CDCA), the agonists of LXR,
      RXR, FXR, respectively. Gene expressions were detected. RESULTS: Biliary
      cholesterol % molar and CSI increased significantly in GS group [(7.98 +/- 0.44)
      mol% vs (4.87 +/- 0.39) mol%, P < 0.01]. Megalin expression in GS group was
      significantly higher than that in GSF group (P < 0.05) and cubilin expression was
      similar between two groups. In vitro experiments showed that CDCA markedly
      increased expression of megalin. CONCLUSION: This study shows that the increased
      expression Megalin may help to increase cholesterol uptake in gallbladder and
      play a compensative role in GS. FXR may participate in the transcription
      regulating of Megalin.

PMID- 19595143
TI  - [Preliminary exploration of transcription factor Nkx2.5 mutations and congenital
      heart diseases].
AB  - OBJECTIVE: To explore the association between the gene mutation of transcription
      factor Nkx2.5 and Chinese patients with congenital heart disease (CHD). METHODS:
      Polymerase chain reaction (PCR) and DNA sequencing were used to check 99 CHD
      patients and 90 normal control subjects from the Zhong Da Hospital of Southeast
      University. After amplifying the exons 1 of the Nkx2.5 gene by PCR, we purified
      the PCR products and conducted the sequencing reaction, analyzed the mutation
      screening of the exon 1 of the Nkx2.5, investigated whether or not the Nkx2.5 is
      related with the CHD in Chinese population. RESULTS: A mutation (A239G) in the
      exon 1 of the Nkx2.5 was identified in 3 of 90 normal control subjects and 12 of
      99 CHD patients, including 3 of 24 with VSD, 7 of 35 with ASD, 1 of 13 with PS
      and 1 of 21 with PDA. CONCLUSION: There are some associations between the Nkx2.5
      gene mutation and occurrence of congenital heart disease in Chinese people.

PMID- 19595147
TI  - [Analysis of 10 cases died from the acute infectious disease with the severe
      adrenalitis, necrosis and hemorrhage].
AB  - OBJECTIVE: To discuss the potential mechanisms and the role of adrenalitis with
      extensive hemorrhage and necrosis in acute critical infectious diseases. Methods
      Forensic autopsy cases from 1987 to 2007 were retrospectively analyzed. And 10
      cases of them were involved in the primary and critical infection with acute
      inflammation, hemorrhage and necrosis of adrenal glands. Results Clinical
      diagnoses of 10 cases were respiratory tract infection (n=6), septic shock (n=2),
      acute esophagitis (n=1), and undefined causes (n=1), and the quickly aggravating
      conditions resulted in death ultimately. However, systematic autopsy confirmed
      that 7 cases died of acute lymphocytic pancarditis, 2 cases acute and lymphocytic
      interstitial pneumonia and 1 case epidemic cerebrospinal meningitis with
      septicemia. And severe complications of all cases included hemorrhagic
      necrotizing adrenalitis, systemic inflammatory response syndrome and multiple
      organ failure (MOF). Conclusions Hemorrhagic necrotizing adrenalitis should be
      considered as one of the important pathological changes in fatal MOF resulting
      from severe infection and trauma etc. More attention should be paid in clinical
      treatment.

PMID- 19595144
TI  - [Features of insulin secretion and insulin resistance in newly diagnosed type 2
      diabetes of different body mass indices].
AB  - OBJECTIVE: To investigate insulin secretion function and insulin resistance in
      Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order
      to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2
      diabetes and 40 normal controls were recruited. Height, weight were measured,
      insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose
      tolerance test were examined. The patients with fasting glucose level greater
      than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After
      normalization of the plasma glucose levels for more than 2 weeks, and withdraw
      this medication for 48 hours, then OGTT were repeated to assess IR and IS.
      RESULTS: The patients were divided into four groups based on fasting plasma
      glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3
      mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were
      further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin
      sensitivity and insulin secretion function compared between subgroups. (1) True
      insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than
      control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI >
      or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24
      groups', but their insulin secretion function were better at the same FPG level.
      (3) After intervention, the change of insulin sensitivity in BMI < 24 group was
      better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural
      logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24
      group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin
      sensitivity and insulin secretion function were decreased with the increase of
      FPG, but they were different between obese and non-obese group. (2) Insulin
      secretion function was recovered better in obese group when eliminated glucose
      toxicity.

PMID- 19595145
TI  - [Side effects of non-steroidal anti-inflammatory drugs on gastric mucosa and
      preventive effects of teprenone].
AB  - OBJECTIVE: To evaluate the side effects of non-steroidal anti-inflammatory drugs
      (NSAID) on gastric mucosa, and to study the preventive effects of teprenone in
      patients. METHODS: 108 patients taking NSAID for more than 3 months with no
      infection of helicobacter pylori (Hp) were collected. All patients were screened
      by endoscopy and their upper gastrointestinal symptoms were evaluated. Then, 16
      patients with ulcers were excluded and 92 patients were randomly divided into
      intervention group with teprenone and control group. After follow-up for 3
      months, patients were screened again by endoscopy and their upper
      gastrointestinal symptoms were also evaluated. Specimens of gastric mucosa were
      studied by PAS dyeing, and Cyclooxygenase (COX) level were evaluated by
      immunohistochemical technique. RESULTS: Of patients taking NSAIDs, the erosion
      was found in 48 (44.4%) patients while 16 (14.8%) were found with peptic ulcers.
      The damages were improved significantly (Z = -4.96, P = 0.000) in the
      intervention group with teprenone (n = 45) as compared with control group (n =
      47) after follow-up for 3 months. Both the cox-1 level [31.1% (14/45) vs 6.7%
      (3/45), P = 0.003] and mucus thickness [66.7% (30/45) vs 13.3% (6/45), P= 0.000]
      also increased in the intervention group as compared with control group. No
      significant difference was found on COX-2 level between these two groups [28.9%
      (13/45) vs 31.1% (14/45), P = 0.82]. CONCLUSION: Long-term use of NSAID caused
      severe damages on gastric and duodenal mucosa; teprenone improved NSAID-related
      gastric side effects and increased the COX-1 level and mucus thickness.

PMID- 19595148
TI  - [Construction of oxalate-degrading intestinal stem cell population in mice].
AB  - OBJECTIVE: The oxalate-degradation genes of Oxalobacter formigenes (Ox.F)-frc
      gene and oxc gene-were cloned and transfected into intestinal stem cell
      population of the mouse to make the latter obtain oxalate-degradation function.
      METHODS: (1) The dicistronic eukaryotic expression vector, which could express
      oxc gene and frc gene in the same time, pIRES-oxc-frc was constructed. (2) The
      intestinal stem cell population of the mouse were isolated and cultured, and the
      function of the cell growth and differentiation was identified. (3) The cells
      were transfected with pIRES-oxc-frc. After selection by G418, the function of the
      cell growth and differentiation and the the expression of the objective genes
      were identified. (4) The concentration of the oxalate in the culture medium which
      was used to culture the transgenic cells was determined by ion chromatography to
      explore the oxalate-degradation function of the cells. RESULTS: Ox.F could be
      isolated and cultured from the feces of Chinese people. Compared with the foreign
      reports, a certain morphologic variation of the Ox.F existed. But the oxc gene
      and frc gene showed high homology with the sequence reported in GenBank. The
      recombinant plasmid containing oxc gene and frc gene could successfully be
      transfected into the intestinal stem cell population of the mouse. The expression
      of the objective genes was normal. The concentration of the oxalate in the
      culture fluid of the transgenic intestinal stem cell population [(2.48 +/- 0.03
      g/L)] was lower than those of the normal group [(2.69 +/- 0.01) g/L] and the
      control group [(2.69 +/- 0.01) g/L, P < 0.01]. CONCLUSION: The oxc gene and the
      frc gene could be transfected into the intestinal stem cell population of the
      mouse, and the cells could be given oxalate-degrading function. The gene of
      prokaryocyte could be introduced into the eukaryocyte for a successful
      expression.

PMID- 19595149
TI  - [Decellularization technology application in whole liver reconstruct biological
      scaffold].
AB  - OBJECTIVE: To explore an innovative method for preparation of a whole-liver
      reconstruct scaffold with intact three-dimensional geometry, vasculature and bile
      duct by decellularization technology. METHODS: The portal vein was annulated and
      perfused sequentially with 1%Triton X-100 and 1%SDS for about 4 h, and then was
      perfused with phosphate buffered saline to dilute SDS residue. The retained
      structure was evaluated by histological analyses, including macroscopic,
      Hematoxylin-Eosin staining, Masson's trichrome staining, orcein staining and SEM.
      The liquid polymer preparation 8% - 10%, which was made of chlorinated poly vinyl
      chloride (CPVC as solute), acetone (as solvent) and pigment, was injected into
      portal vein and bile duct to demonstrate the integrity of the portal vein and
      bile duct. The scaffold was cut into slices with the thickness of about 50 microm
      and cocultured with C3A cell line. RESULTS: Macroscopic examination showed that
      the decellularized liver was transparent and intrahepatic Glisson's system could
      be observed. H&E staining of slices of decellularized liver demonstrated no
      intact cells or nuclei existed. Masson trichrome staining revealed collagen
      retained. Orcein staining showed that there were elastic fibers. SEM showed the
      network of ECM was intact. C3A-to-scaffold co-culture revealed the scaffold of
      good biocompatibility. CONCLUSION: Perfusion with detergents through portal vein
      for liver decellularization was an efficient method to obtain a completely whole
      liver scaffold which can be used for hepatic organ reconstruction.

PMID- 19595150
TI  - [Growth hormone influence on functional status of cord blood-derived dendritic
      cells].
AB  - OBJECTIVE: To detect the effect of functional status and immunophenotype of
      dendritic cell modified with growth hormone (GH) from by cord blood. METHODS:
      Monocyte was isolated from cord blood, DCs were induced with IL-4 & GM-CSF and
      modified with different concentration of GH. The morphology, count and growth
      status of DC were observed appearance. And the immunophenotype of DC was detected
      with flow cytometry. IL-12 in supernatant was measured with ELISA. The immuno
      activity was determined with autologous mixed lymphocyte reaction. RESULTS:
      Mature DC were induced from adherent lymphomonocyte under the action of IL-4, GM
      CSF and GH of different densities (5, 25, 100 ng/ml). GH increased the positive
      expression of CD83 (31% +/- 4%, 34% +/- 4%, 34% +/- 5%), CD80 (26% +/- 4%, 29% +/
      6%, 30% +/- 6%)and HLA-DR (45% +/- 8%, 49% +/- 6%, 50% +/- 5%) (P < 0.05),
      enhanced the ability of secreting IL-12 (P < 0.05), and boosted significantly the
      immuno-activation of DC to autologous lymphocyte (P < 0.05). CONCLUSION: GH could
      promote the differentiation, maturation and the expression of costimulatory
      molecules, increase the IL-12 production in DC and enhanced the ability of DC to
      stimulate the proliferation of lymphocyte within a certain dose range.

PMID- 19595151
TI  - [Effect of Shenmai injection on expression of hypoxia-inducible factor-1alpha in
      hypoxic-ischemic brain damage: experiment with rats].
AB  - OBJECTIVE: To investigate the effects of Shenmai injection containing active
      principles of Ginseng and ophiopogon root on the expression of hypoxia-inducible
      factor 1-alpha (HIF-1alpha) in brain after hypoxic-ischemic brain damage (HIBD).
      METHODS: 108 neonatal SD rats were randomly divided into 2 equal groups: (1)
      Shenmai group (Group SM), undergoing ligation of the right common carotid artery
      to establish HIBD models, breathing immediately a mixed gas with 8% oxygen and
      92% nitrogen for 2 hours to cause HI insult, and then injected intraperitoneally
      with Shenmai injection 10 mg/kg once a day for 7 days, and (2) normal saline (NS)
      group (Group NS) undergoing ligation of the right common carotid artery to
      establish HIBD models, breathing immediately a mixed gas with 8% oxygen and 92%
      nitrogen for 2 h, and then injected intraperitoneally with NS 10 mg/kg once a day
      for 7 days. Another 54 neonatal rats underwent sham operation but did not undergo
      hypoxia as control group (Group C), 2, 12, and 24 hours, and 3, 7, and 14 days
      after HI insult 9 rats from each group were killed with their right hippocampal
      tissues taken out. Flow cytometry was used to examine the apoptotic rate of the
      hippocampal neurons. RT-PCR was used to detect the mRNA expression of HIF-1alpha.
      RESULTS: (1) The apoptosis rate of the right hippocampal tissues began increase 2
      h after Hi insult, peaked 24 h after HI, then gradually decreased, and almost
      returned to the original levels 14 d after HI. There was no significant
      differences in apoptosis rates 14d after HI among the 3 groups (all P > 0.05).
      The neuron apoptosis rates 12 h, 24 h, 3 d, and 7 d after HI of Group SM were all
      significantly lower than those of Group NS (e.g 24 h: (11.95 +/- 1.13)% vs (16.80
      +/- 1.44)%, all P < 0.05). (2) The HIF-1alpha mRNA expression level in right
      brain began to increase 2 h after HI, peaked 24 h after HI, then gradually
      decreases, and returned to the original level 14 d after Hi in both Group SM and
      Group NS; The HIF-1alpha mRNA expression in right brain 12 h, 24 h, 3 d, and 7 d
      after HI of Group SM were all significantly higher than those of Group NS (e.g 24
      h: (44.32 +/- 4.03)% vs (35.63 +/- 3.73)%, all P < 0.05). CONCLUSION: The HIF
      1alpha mRNA expression in brain tissue is up-regulated after HI insult. Shenmai
      injection helps increase the mRNA expression of HIF-1alpha in brain and reduces
      the apoptosis of hippocampus neurons after HI insult.

PMID- 19595154
TI  - [Epidemiology of anticoagulation for hemodialysis patients: survey of 842 cases
      in seven hemodialysis centers].
AB  - OBJECTIVE: To investigate the anticoagulant methods and characters of
      hemodialysis patients in hospitals of Grade III Level A. METHODS: A questionnaire
      survey was conducted in 7 hemodialysis centers of class 3 first level general
      hospital in Beijing, Shenyang, Harbin, and Dalian, on the hemodialysis status,
      primary diseases, anticoagulation methods, and complications. RESULTS: 808 of the
      842 patients (95.9%) underwent hemodialysis, and 34 patients (4.1%) were
      subjected to hemodialysis filtration. 606 hemodialysis patients (74.9%) used
      heparin as the anticoagulant, and the doses and using method were different among
      different centers. 223 patients (26.5%) used low molecular weight heparin (LMWH)
      with different kinds, doses and using methods. The underlying diseases included
      diabetes (15.1%), hypertension (9.4%), and other diseases (75.5%). There was no
      significant difference in the dosage of heparin among different diseases, while
      the dosage of LMWH was lower for the diabetes and hypertension patients. 171
      patients (20.3%) had hemorrhagic tendency, and 67 patients (20.3%) suffered from
      thrombus. The dosage of heparin was lower in the patients with hemorrhagic
      tendency while no difference was found in the dosages of LMWH among the patients
      with different diseases. Antiplatelet agents were co-administrated in 172
      hemodialysis patients (20.4%). The percentages of co-administration of
      antiplatelet for patients with thrombus and hemorrhagic tendency were 14% and
      12.8% respectively. The dosages of heparin and LMWH were higher in the patients
      with co-administration than those without co-administration. Coagulation marker
      examination was conducted in only 385 patients (45.7%), and no difference in the
      frequency of coagulation marker examination was found among the patients with
      hemorrhagic tendency, thrombus, and other diseases. CONCLUSION: Heparin is the
      main anticoagulant in hemodialysis. The anticoagulant methodology in hemodialysis
      is still empirical without clotting monitor and standard for usage of
      anticoagulants.

PMID- 19595155
TI  - [Polymorphism of glutathione S-transferase P1 and correlation there of with
      carcinogenesis risk of gastric intestinal metaplasia].
AB  - OBJECTIVE: To investigate the distribution of polymorphism of glutathione S
      transferase P1 (GSTP1) in different kinds gastric intestinal metaplasia (IM), and
      the carcinogenesis risk of different types of IM. METHODS: Peripheral blood
      samples were collected from 87 gastric cancer patients, 87 intestinal metaplasia
      patients, and 87 healthy persons as controls. Polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) were used to analyze the
      distribution of different alleles of GSTP1. Biopsy specimens of gastric mucous
      membrane were collected by gastroscopy. Histochemical staining for mucin was used
      to identify the kinds of IM. RESULTS: The G allele rates of the IM and gastric
      cancer groups were both significantly higher than that of the control group
      (chi2=6.921, P=0.009; chi2=28.787, P=0.000). The risk of IM of those with G
      allele was 1.944 times higher then that of the normal controls (95% CI: 1.177
      3.209), and the risk of gastric cancer of those with G allele was 3.605 times
      higher (95% CI: 2.217-5.863). The G allele rate of the gastric cancer group was
      significantly higher than that of he IM group (chi2=7.687, P=0.006). The G allele
      rates of the type II and III IM were significantly higher than that of the normal
      controls (chi2=9.981, P=0.001; chi2=8.845, P=0.002). The risk of type II IM of
      the subjects with G allele was 2.747 times higher than that of the normal
      controls (95% CI: 1.475-5.114), and the risk of type III IM of the subjects with
      G allele was 3.451 times higher (95% CI: 1.556-7.657). The risks of type IIIM,
      type III IM, and gastric cancer of the subjects with allele G of GSTP1 gene were
      2.905, 3.650, and 3.813 times higher than those of the normal controls
      respectively (95% CI: 1.341-6.293, 1.455-9.153 and 1.953-7.444 respectively).
      CONCLUSION: The individuals with G allele show an increased risk of developing IM
      and gastric cancer, especially type II and III IM. IM patients with G allele have
      the genetic characteristics similar to those of gastric cancer, so they should be
      regarded as high-risk individuals of gastric cancer and followed up regularly.

PMID- 19595156
TI  - [Inspection on angiogenesis in malignant transformation of breast tumor by
      ultrasound contrast and quantitative analysis].
AB  - OBJECTIVE: To study the effects of angiogenesis on tumorigenesis and the
      progression of breast carcinoma and precancerous lesion. METHODS: Real time
      ultrasound contrast enhanced microvascular imaging (MVI) and time-intensity curve
      quantitative analysis were conducted on 30 normal controls, 30 cases with simple
      hyperplasia, 30 cases with atypical hyperplasia (AH), 20 cases with intraductal
      carcinoma in situ, and 50 cases with invasive ductal carcinoma, all female.
      Specimens of breast tissues were obtained and immunohistochemistry was used to
      detect the expression of CD34, a marker of vascular endothelial cells, and
      vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR. RESULTS:
      With the progression of malignant transformation of breast tissue, the expression
      levels of VEGF and Flk-1/KDR increased gradually, the framework of the vessels
      became disordered, the levels of MVD and the perfusion parameters, such as peak
      intensity (PI), area under the curve (AUC), and wash-out time (WOT), increased.
      Obvious changes in these parameters began since the AH stage. There were not
      significant differences in the PI, AUC, and WOT levels between the groups of AH
      and in situ cancer, however, the VEGF and Flk-1/KDR levels of the in situ
      carcinoma group were significantly higher than those of the AH group (both
      P<0.05). CONCLUSION: Angiogenesis plays an important role in the development of
      breast carcinoma. Contrast MVI and the main perfusion parameters reflect the rule
      of angiogenesis activity changing in different precancerous lesions, and can be
      used as non-invasive methods to screen high risk population.

PMID- 19595157
TI  - [The value of breath-hold diffusion-weighted imaging in small hepatocellular
      carcinoma lesion (<or=3 cm) detection].
AB  - OBJECTIVE: To evaluate the added value of single breath-hold diffusion-weighted
      imaging (DWI) in detection of small HCC lesions (<or=3 cm) in patients with
      chronic liver disease, by comparing the detection sensitivity of DWI/conventional
      dynamic contrast enhancement (DCE) MRI and that of conventional DCE MRI alone.
      METHODS: A total of 54 patients with chronic liver diseases underwent abdominal
      MRI at 1.5 T, including T1-weighted (T1WI), T2-weighted (T2WI), and 2D
      conventional DCE. For each patient study, axial DWI was performed with a single
      shot echo-planar imaging (EPI) sequence using modified sensitivity encoding
      (mSENSE) with b-value of 500 seconds/mm2. A total of 20-24 slices were obtained
      during a 15-17-second breath-hold. Two observers independently interpreted the
      combined DWI/conventional DCE MRI images and the conventional DCE MRI images in
      random order. For all small HCC lesions and micro-hepatocellular carcinoma
      (smaller than 10 mm MHCC), the diagnostic performance using each imaging
      techniques were evaluated by ROC analysis. Sensitivity and positive predictive
      values were also calculated. RESULTS: The mean areas under the ROC curve (Az) of
      combined DWI/conventional DCE MRI images (0.945, 0.86) were statistically higher
      than those of conventional DCE MRI alone (0.86, 0.64) for all small HCC lesions
      and MHCC (micro hepatocellular carcinoma) lesions (P<0.01). The lesion detection
      sensitivities using the combined technique of both observers were significantly
      higher than those using the conventional DCE MRI alone for all small lesions and
      for MHCC (P<0.01). For MHCC, the sensitivities using the combined technique and
      the conventional DCE MRI alone were 95.8%-96.0% and 62.5%-68.0%, respectively.
      The positive predictive values for MHCC using the combined imaging technique
      (95.8%-96.0%) were higher than those using the conventional DCE MRI alone (94.1%
      94.4%) (P<0.05). For all small HCC lesions, the positive predictive values using
      the combined imaging technique and the conventional DCE MRI alone were 98.6%
      98.7% and 95.5%-95.7%, respectively and there was no statistical difference.
      CONCLUSION: Combined use of Breath-hold DWI with conventional DCE MRI helped to
      provide higher sensitivities than conventional DCE MRI alone in the detection of
      small HCC lesions in patients with chronic liver disease. Furthermore, DWI could
      provide additional valuable information that benefits the differential diagnosis.

PMID- 19595158
TI  - [Single-stage posterior vertebrectomy with reconstruction in treatment of spinal
      tumor].
AB  - OBJECTIVE: To investigate the feasibility and clinical significance of single
      stage posterior vertebrectomy with reconstruction for the treatment of spinal
      tumor. METHODS: Twenty-six consecutive patients with spinal tumor, 5 with giant
      cell tumor, 6 with metastatic tumor of breast cancer, 8 with metastatic tumor of
      lung cancer, 2 with plasmacytoma, 3 with metastatic tumor of renal carcinoma, and
      2 with lymphoma, 12 males and 14 females, aged 49 (20-74), underwent single-stage
      posterior vertebrectomy through bilateral transpedicular route via posterior
      midline approach. Anterior column reconstruction was performed with non
      expandable cages. Anterior and posterolateral arthrodeses were achieved using
      autograft. Posterior segmental instrumentation was used in all cases. Follow-up
      was conducted for 10-48 months. RESULTS: The mean operative time was 4.5 hours
      and the mean blood loss was 1600 ml. Sagittal deformity correction was performed
      for the four patients with preoperative kyphosis. 15 patients were neurologically
      intact preoperatively (at Frankel grade E) and remained intact postoperatively.
      11 patients with functional disorders of spinal cord or nerves (Frankel grade D)
      preoperatively showed improvement to Frankel grade E postoperatively. Local pain
      disappeared in 19 patients and reduced in 7 patients. CONCLUSION: A safe and
      effective technique for the treatment of spinal tumor, single-stage posterior
      vertebrectomy with reconstruction fully decompresses the neurological structures,
      corrects kyphosis, and achieves early weight-bearing, thus significantly
      improving the quality of life of the patients with spinal tumor.

PMID- 19595159
TI  - [Measurement of humeral head retroversion angle with multislice spiral
      computerized tomography volume rendering technique].
AB  - OBJECTIVE: To verify the accuracy of measurement of humeral head retroversion
      angle with multislice spiral computerized tomography (MSCT) volume rendering
      technique. METHODS: Twenty cadaveric humeri, 9 left and 11 right, free from
      traumatic or degenerative disfigurement, were harvested from embalmed cadavers.
      Before all soft tissues were removed by sharp dissection these humeri were
      scanned with 16 slice spiral CT scanner (CT1 group); then underwent anatomical
      measurement (anatomical measuring group); and at last, these humeri with marked
      anatomic neck were scanned with 16 slice spiral CT scanner again (CT2 group). The
      measurement was done by 2 orthopedists independently so as to diminish the
      measuring error. The differences in the humeral head retroversion angle between
      the CT1 group and anatomical measuring group, and the CT2 group and anatomical
      measuring group were analyzed with paired-samples T test. RESULTS: It showed that
      the results have no significant difference among them. The difference in the
      average value of humeral head retroversion angle between the CT1 group and
      anatomical measuring group was 1.64 degrees, and that between the CT2 group and
      anatomical measuring group was 0.65 degrees. CONCLUSION: Simple, fast, and
      precise, and suitable for clinical application, MSCT volume rendering technique
      can be used preoperatively, thus helping to realize the idea of individualization
      of shoulder arthroplasty and shoulder prosthesis. Although this technique is easy
      to be influence by the subjective factors of the observers, increase of
      experience and rational measurement may minimize the measurement error.

PMID- 19595160
TI  - [Long-term outcome of operatively and non-operatively managed high-grade
      intracranial arteriovenous malformations and factors influencing postoperative
      neurological deficits].
AB  - OBJECTIVE: To compare the effects of surgical and non-surgical treatments for
      high-grade intracranial arteriovenous malformation (AVM), identify the
      determinants of neurological function deterioration after surgery, and calculate
      the annual hemorrhage rate. METHODS: 98 high-grade intracranial AVM patients
      underwent surgery, and 44 high-grade intracranial AVM patients underwent
      conservative treatment. Follow-up was conducted on 141 of these 142 patients for
      (54+/-36) (6-118) months. MRI and DSA were conducted before and/or after
      treatment on most of the patients. Glasgow outcome score (GOS) was used to
      evaluate the neurological functions early and more then 6 months after discharge.
      The clinical data of these 142 patients were retrospectively analyzed. The annual
      hemorrhage rate associated with these lesions was calculated. RESULTS: The annual
      hemorrhage rate of these 142 patients was 2.1%. The integrated rate of late
      disability and mortality of the operative group was 10.1%, remarkably higher than
      that of the non-operative group (25.0%). AVM size, adjacent brain functional
      region, Spetzler-Martin grade, deep perforating arterial supply, and intra
      operative bleeding volume were significantly correlated with early and permanent
      neurological function deficits. CONCLUSION: The long-term outcome of operatively
      managed intracranial high-grade AVMs is superior to that of the non-operatively
      treated ones. Spetzler-Martin grade and deep arterial perforating supply are the
      most important determinants of neurological deficit after microsurgical resection
      of AVM.

PMID- 19595161
TI  - [Spatial nature of mental number line in neglect patients].
AB  - OBJECTIVE: To investigate the spatial nature of mental number line. METHODS:
      Number bisection test was conducted on 8 right-brain-damaged patients with
      persistent left neglect, 8 right-brain-damaged patients without spatial neglect,
      and 8 healthy control subjects, all aged- and education-level-matched and right
      handed. RESULTS: The error rate in subjective midpoint of the 8 neglect patients
      was (44.63+/-12.49)% (forward direction) and (46.00+/-12.10)% (reverse
      direction), both significantly higher than those of the right brain damage
      control group [(3.34+/-4.32)% and (5.21+/-5.21)% respectively] and healthy
      control group [(0.00+/-0.00)% and (0.00+/-0.00)% respectively] (all P<0.01). The
      longer the interval between the numbers, the higher right-shift error rate:
      corresponding to the interval sizes as 3, 5, 7, and 9, the mean deviation rates
      of anthrone presentation were (-4.25+/-7.87)%, (12.63+/-19.06)%, (58.38+/
      24.30)%, and (111.50+/-53.54)% respectively, and the mean deviation rates of
      reverse presentation were (-18.40+/-25.35)%, (-1.60+/-21.4)%, (56.80+/-27.04)%,
      and (108.20+/-55.10)% respectively. Analysis of variance of the anthrone
      presentation and reverse presentation showed the result: F=1.705 and P=0.262.
      Correlation analysis of the mental number bisection task and line bisection task
      showed the result: r=0.887 and P=0.045. The control subjects made very few errors
      in subjective midpoint and their performance was not affected by interval sizes.
      The magnitude of numbers used did not influence the performance in any group.
      CONCLUSION: The performance of neglect patients in bisecting mental number line
      closely mirrors their difficulty in bisecting physical lines. This demonstrates
      the spatial nature of the mental number line isomorphism to physical lines. The
      mental number line is orientated in a left-to-right manner. Disorder exists at
      the characterization level in neglect patients.

PMID- 19595162
TI  - [Effects of different mutated sites in vpr gene of HIV on apoptosis of host
      cells: experiment with HeLa cells].
AB  - OBJECTIVE: To investigate the effects of different mutated sites in the vpr gene
      of HIV on the apoptosis of host cells, and the possible mechanism thereof.
      METHODS: Fourteen HIV-1 vpr fragments were obtained from HIV-infected persons.
      Eukaryotic expression vector pcDNA3.1 (+) plasmid was extracted, the PCR purified
      product was double-cut by HindIII and BamH, and the cut products were ligated to
      vectors, thus establishing the JM109 competent cells. Sequencing was used to
      confirm the reconstruction of pcDNA-vpr eukaryotic expression vectors that were
      then transfected into HeLa cells. Blank vectors were transfected as control
      group. Cells were harvested after 24 hours and underwent Hoechst 33258 staining
      and observed under fluorescence microscope. Annexin-FITC-PI staining and flow
      cytometry were used to observe the percentage of apoptosis. The caspase-3
      activity was detected by enzyme labeling instrument. RESULTS: The apoptotic rates
      shown by Hoechst and annexin--FITC-PI staining methods, and caspase-3 activity
      levels of the HeLa cells transfected with the gene fragments with mutated sites
      70, 85, 86, and 94 cells were all lower than the cells transfected with the gene
      fragments without these mutated sites. The apoptosis causing ability levels of
      the No 1-7 recombinant plasmids (all of the Vpr AE subtype) were all lower than
      those of the No 8-14 plasmids (of Vpr B, AB, C, and C/BC subtypes). CONCLUSION:
      The apoptosis causing ability of the HIV with the vpr sequence with mutated sites
      70, 85, 86, 94 is significantly lower than those without these sites. AE subtype
      induces lower apoptotic behavior in the hoist cells, and decreased activation of
      the caspase-3 pathway may be one of the mechanisms.

PMID- 19595163
TI  - [Neuronal activity of ventrolateral thalamus in patients with essential tremor].
AB  - OBJECTIVE: To investigate the neuronal activity in the ventrolateral thalamus in
      relation to essential tremor (ET). METHODS: Microelectrode recording in the
      ventral oral posterior (Vop) and ventral intermediate nucleus (Vim) of thalamus
      was performed on 10 patients with ET and 10 patients with Parkinson's disease
      (PD) who underwent thalamotomy for tremor during operation. Electromyography
      (EMG) was carried out on the contralateral limbs simultaneously. Single unit
      analysis was performed to measure the interspike interval (ISI) and histogram was
      constructed to evaluate the pattern of neuronal activity. Student t-test was
      employed to compare the mean spontaneous firing rate (MSFR) and ISI of neuronal
      firing in Vop/Vim between the ET patients and PD patients. and correlation test.
      RESULTS: Two hundred and sixty-six neurons were identified from 20 trajectories,
      38.0% being neurons with tremor-related neuronal activity Tremor cells, 31.9% of
      neurons related to tonic firing, and 30.1% of neurons related to irregular
      discharge. 131 of these thalamic neurons, were obtained from 10 ET patients. 38
      of these 131 neurons (29.0%) were related to tremor-related neuronal activity, 54
      (41.2%) neurons were related to tonic firing with a mean spontaneous firing rate
      (MSFR) of (55+/-21) Hz, and 39 neurons (29.8%) were related to irregular
      discharge with a MSFR of (32+/-17) Hz. In the meantime, 135 neurons were obtained
      from 10 PD patients. Of these 135 neurons 63 (46.7%) were related to tremor, 31
      neurons (23.0%) related to tonic firing with a MSFR of (39+/-15) Hz, and 41
      (30.3%) were related to irregular discharge with a MSFR of (21+/-8) Hz. The MSFR
      levels of pooled neurons in Vop/Vim with tonic firing and irregular discharge of
      the ET patients were significantly higher than those of the PD patents (t=2.74
      and 2.99, both P<0.05). And the MSFR levels in Vop and Vim of the ET patients
      were significantly higher than those of the PD patients (both P<0.05).
      CONCLUSION: Vim receives the projection from cerebellum. The increase of neuronal
      firing frequency observed in Vim suggests that the pathophysiology of ET may be
      correlated with excessive activity of cerebellum.

PMID- 19595164
TI  - [Protective effects of micro-encapsulated Bifidobacteria on gut barrier after
      hemorrhagic shock and resuscitation: experiment with rats].
AB  - OBJECTIVE: To investigate the effects of micro-encapsulated bifidobacteria on gut
      barrier and bacterial translocation after hemorrhagic shock and resuscitation.
      METHODS: Sprague-Dawley rats were divided into 6 groups: PBS+sham shock group fed
      with PBS for 7 days and then undergoing sham shock, bifidobacteria+sham shock
      group fed with bifidobacteria (10(9) cfu/d) for 7 days and then undergoing sham
      shock, micro-encapsulated bifidobacteria+sham shock group, fed with micro
      encapsulated bifidobacteria (10(9) cfu/d) for 7 days and then undergoing sham
      shock, PBS+hemorrhagic shock group fed with PBS for 7 days and then undergoing
      hemorrhagic shock, bifidobacteria+shock group fed with bifidobacteria for 7 days
      and then undergoing hemorrhagic shock, and micro-encapsulated
      bifidobacteria+shock group, fed with micro-encapsulated bifidobacteria for 7 days
      and then undergoing hemorrhagic shock. Three hours after resuscitation laparotomy
      was performed, distal cecum was resected to undergo bacteriological analysis of
      the cecal content, mesenteric lymph nodes (MLNs), a liver lobe, and the middle
      part of spleen were resected to undergo bacterial culture for bacterial
      translocation, and the terminal ileum was resected to observe the villous damage.
      RESULTS: There was no significant difference in the amount of blood loss among
      the 3 hemorrhagic shock groups. The amounts of aerobes in cecum of the
      bifidobacteria+shock and micro-encapsulated bifidobacteria+shock groups,
      especially that of the latter group, were significantly lower than that of the
      PBS+shock group. The amounts of anaerobes and the amounts of bifidobacteria in
      cecum of the bifidobacteria+shock group and micro-encapsulated
      bifidobacteria+shock group, especially those of the latter group, were
      significantly higher than those of the PBS+shock group. No bacterial
      translocation to liver was observed in all groups. The magnitudes of total
      aerobes translocation in spleen of the bifidobacteria+shock and encapsulated
      bifidobacteria+shock groups were significantly lower than that of the PBS+shock
      group, however, there were not significant differences in the translocation in
      the MLN of total aerobes ad bifidobacteria among different groups. The percentage
      of ileal villous damage of the bifidobacteria+shock and encapsulated
      bifidobacteria+shock groups were significantly lower than that of the PBS+shock
      group. CONCLUSION: Bifidobacteria effectively protects the gut barrier, reduces
      bacterial translocation from the gut after hemorrhagic shock and resuscitation.
      And micro-encapsulated Bifidobacteria can enhance those effects further.

PMID- 19595165
TI  - [Effects of ovarian carcinoma cells on the maturation and function of human
      dendritic cells].
AB  - OBJECTIVE: To investigate the effects of ovarian carcinoma cells on the
      differentiation, maturation, and function of the dendritic cells (DC). METHODS:
      Human epithelial ovarian carcinoma cells were isolated from specimens of ovarian
      carcinoma from 12 patients obtained during operation, and cultured. Peripheral
      blood samples were collected from these patients. DC were isolated and co
      cultured with recombinant human tumor necrosis factor (TNF)-alpha to promote
      their maturation. Immunostaining and flow cytometry (FC) were used to detect the
      DC specific marker CD1a, maturation marker CD83, co-stimulating factors CD86 and
      human leucocyte antigen (HLA)-DR. FITC-labeled glucan was added and FC was used
      to detect the phagocytic function. T cells were co-cultured with immature and
      mature DC of different concentrations respectively for 96 h, 18 h before the end
      of culture 3H-TdR was added, liquid scintillation counter was used to measure the
      level of count per minute (cpm) Ovarian carcinoma cells and peripheral
      mononuclear cells were put into Transwell to contact each other directly or
      indirectly, TNF-alpha was add to promote the maturation, and then FC was used to
      detect the CD1a, CD83, CD86, and HLA-DR levels, and the glucan uptake level.
      ELISA was used to detect the levels of IL-12, IL-10, and interferon (IFN)-gamma,
      and Western blotting was used to detect the p-38 protein and phosphorylated p-38
      protein in the supernatant. RESULTS: After stimulation of TNF-alpha the
      expression; levels of CD1a, CD86, CD83, and HLA-DR of the DCs were remarkably
      increased. Immature DCs showed a strong ability at phagocytosis of glucan, and
      this ability was decreased by the stimulation of TNF-alpha. The proliferative
      function of mature DCs on allogenic T lymphocytes was significantly increased
      dose-dependently (P<0.05). Co-culture with ovarian carcinoma cells decreased the
      expression levels of CD1a, CD86, and HLA-DR, increased the expression level of
      CD83, and decreased the ability in up taking glucan by 43.05%. The proliferative
      function of the DC cultured in direct contact with ovarian carcinoma cells was
      decreased by 56.35%, and such inhibitory function of the DCs cultured not in
      direct contact with ovarian carcinoma cells was weaker, and the levels of CD1a,
      CD86, CD83, and HLA-DR expressed by the DC cultured not in direct contact with
      ovarian carcinoma cells was between those of the DC cultured in direct contact
      with ovarian carcinoma cells and those of the DC undergoing routine culture. The
      levels of IL-12 and phosphorylated p-38 protein were decreased in the supernatant
      of the DC co-cultured with ovarian carcinoma cells. CONCLUSION: Ovarian carcinoma
      cells suppress the differentiation of monocyte into DC, negatively regulates the
      phagocytotic and antaean managing functions of DC, thus the DC can not
      effectively stimulate the proliferation of T lymphocytes and inhibit the activity
      of cytotoxic T lymphocytes. That may be one of the underlying mechanisms of
      immune escape of tumor and immune tolerance of T lymphocytes.

PMID- 19595166
TI  - [Tumor cells lysates pulsed dendritic cells for immunotherapy of ovarian cancer
      in rats: in-vitro study].
AB  - OBJECTIVE: To study the feasibility of ovarian tumor cells lysates pulsed
      dendritic cells (DCs) in the immunotherapy of tumor prevention via cytotoxic test
      in-vitro. METHODS: Forty rats were randomly divided into 2 groups: experimental
      and control groups. Ten rats from each group were killed and DCs were isolated
      and cultured. Frozen-thawed antigen of in the study group, rat's Ovarian cancer
      cells of the line NuTu-19 were cultured, freeze-melt antigens were added at day
      3. Two groups co-cultured with T lymphocytes from the other rat's spleen on the
      14th day. Then observed the shape of DCs, contrasted the proliferation and
      killing rate. RESULTS: In the study group, DCs could significantly stimulate T
      lymphocytes multiplication and produce tumor specific cytotoxic T lymphocytes
      (CTL). When the ratios of stimulating cells (SC) to reaction cells (RC) were 1:3,
      1:10, 1:30 and 1:100, the stimulating index (SI) in the study group were much
      higher than those in control group (P<0.01). When the ratios of SC is the same
      with RC (SC:RC=3:1, 10:1, 30:1): the killing and wounding rate to tumor cells of
      study group [(40.9+/-1.2)%, (69.8+/-1.8)%, (89.0+/-0.4%)] is significantly higher
      than those of control group [(30.9+/-1.9)%, (34.4+/-2.1)%, (51.0+/-1.5)%] (P <
      0.01). CONCLUSION: DC could activate T lymphocytes proliferation and produce CTL
      to kill and wound tumor cells in-vitro.

PMID- 19595171
TI  - [Admission glucose level: an important predictor of prognosis in patients with
      acute myocardial infarction].

PMID- 19595172
TI  - [Significance of blood glucose control in cardiovascular disease risk
      management].

PMID- 19595174
TI  - [Effect of admission blood glucose levels on the short term mortality in patients
      with acute ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To evaluate the predictive value of different admission blood glucose
      levels for short-term mortality in patients with ST-segment elevation acute
      myocardial infarction (STEMI). METHOD: An observational analysis of 7446 Chinese
      STEMI patients from a global randomized controlled trials were recruited within
      12 hours of symptom onset. According to the levels of admission glucose, these
      patients were divided into six groups, admission glucose < 4.50 mmol/L was
      defined as the hypoglycemia group; glucose of 4.5 - 5.5 mmol/L a control; 5.6 -
      7.0 mmol/L, 7.1 - 8.5 mmol/L (mild hyperglycemia group) and 8.6 - 11.0 mmol/L
      (moderate hyperglycemia group); glucose > 11.0 mmol/L was the severe
      hyperglycemia group. The 30-day mortality was analyzed. RESULT: Compared with the
      glucose of 4.5 - 5.5 mmol/L group, thirty-day mortality increased in patients
      with hypoglycemia (10.2%, P < 0.05), mild and moderate hyperglycemia (9.2%, P =
      0.01; 11.6%, P < 0.01, respectively) and severe hyperglycemia (18.6%, P < 0.01).
      The highest mortality occurred in the severe hyperglycemia group. Multivariate
      logistic regression analysis showed that, as compared with glucose of 4.5 - 5.5
      mmol/L, the mild and the moderate hyperglycemia groups had a mortality increasing
      of 46% (OR 1.46, 95% CI 1.03 - 2.07, P = 0.01) and 58% fold (OR 1.58, 95% CI 1.13
      - 2.22 P = 0.02) respectively; the severe hyperglycemia group had a risk of death
      of 2.26 folds (OR 2.26, 95% CI 1.62 - 3.14, P = 0.05). Mild, moderate and severe
      hyperglycemia were independent predictors of 30-day mortality. CONCLUSION: The 30
      day mortality was higher in STEMI patients with mild, moderate and severe
      hyperglycemia at admission. Admission blood glucose level is an important factor
      associated with a short-term.

PMID- 19595175
TI  - [Number and function of circulating endothelial progenitor cell in diabetics with
      different vascular complications].
AB  - OBJECTIVE: To investigate the number and function of circulating endothelial
      progenitor cell (EPC) in different vascular complications of type 2 diabetes
      (T2DM) and its associations with vascular endothelial function. METHODS: A total
      of 415 T2DM patients were recruited from the outpatients and inpatients of the
      Endocrinology Department at Union Hospital. Assessments of cardiovascular disease
      and cerebrovascular disease were based on each patient's medical records.
      Peripheral vascular disease was diagnosed by bilateral ultrasonography
      bilaterally. Non-mydriatic fundus camera screening was used as a tool to identify
      diabetic retinopathy. Urinary albumin exceeding 30 mg/24 h occurring twice over a
      period of six months was diagnosed as diabetic nephropathy. Circulating EPC was
      quantified by flow cytometry. Colony forming count (CFU) and migration assay were
      used for evaluating the function of circulating EPC. Vascular endothelial
      function was assessed by flow-mediated brachial artery dilatation (FMD). RESULTS:
      There were four groups in the study: T2DM without vascular disease (TC, n = 97),
      T2DM with macrovascular disease (TA, n = 106), T2DM with microvascular disease
      (TI, n = 100), T2DM with macro- and micro-vascular diseases (TAI, n = 112). The
      sequence of circulating EPC number and CFU in four groups was TA < TAI < TI < TC
      (532 +/- 90, 616 +/- 93, 768 +/- 97 and 1045 +/- 106 cell/ml; 21 +/- 4, 28 +/- 5,
      43 +/- 7 and 70 +/- 9 unit/chamber) and there was a significant difference
      between any two groups (P < 0.05). The results of migration were consistent with
      circulating EPC number (125 +/- 12; 90 +/- 9 cell/HP field) except there were no
      significant differences in TA and TAI groups (24 +/- 6; 28 +/- 7 cell/HP field).
      Age, HbA1c, SBP, BMI and duration of T2DM were the independent risk factors of
      circulating EPC number in T2DM patients with macrovascular disease (P < 0.05).
      Age, HbA1c and duration of T2DM were the independent risk factors of circulating
      EPC number in T2DM patients with microvascular disease (P < 0.05). After the
      adjustment of traditional risk factors, the number of circulating EPC had a close
      correlation with FMD (standardized coefficient, t = 0.61, P = 0.01). CONCLUSION:
      The number and function of circulating EPC decreased with different degrees in
      T2DM patients of different vascular diseases. Circulating EPC number was
      associated with endothelial function and can be considered as a surrogate
      biological marker of vascular endothelial function for T2DM.

PMID- 19595176
TI  - [Effects of Trimetazidine upon ventricular remodeling and GLUT4 in diabetic rats
      after myocardial infarction].
AB  - OBJECTIVE: The aim of study is to investigate the changes of structure and
      function of heart in diabetic rat after myocardial infarction, and to study the
      expression of the GLUT4 and the effects of trimetazidine on the ventricular
      remodeling. METHODS: Type 2 diabetes rat was made by feeding with a diet enriched
      with sucrose, fat and cholesterol for six weeks and then injecting streptozocin
      intraperitoneally, then the myocardial infarction by ligating coronary artery.
      The living rats were randomly divided into three groups twenty-four hours after
      operation: placebo; trimetazidine and sham operated with diabetes. And other rats
      which was fed with normal diet were divided into myocardial infarction group
      without diabetes and sham operated group without diabete. The treat group was
      intragastric administrated with trimetazidine which was solved in distilled water
      (30 mgxkg(-1) 1xd(-1)), and others were poured with parts aequalis distilled
      water. After six weeks, echocardiographic and hemodynamic studies were performed,
      ventricular were weighed, myocardial infarct size and myocardial collagen volume
      fraction (CVF) of non-infarction area were detected also. GLUT4 mRNA in the
      myocardium away from infarction region were measured with fluorescent
      quantitation RT-PCR and GLUT4 protein were measured with Western blot. RESULTS:
      Six weeks after diabetes complicating with myocardial infarction, comparing with
      sham operated group without diabete, diabetes sham operated group and myocardial
      infarction group without diabete, LVDd of diabetes complicating with myocardial
      infarction group was increased significantly; the systolic and diastolic function
      with left ventricular were decreased significantly, VWI and CVF were increased
      significantly; comparing with placebo group, diastolic function of left
      ventricular in trimetazidine group was improved significantly (4.7 +/- 1.7 vs 6.8
      +/- 1.6, P < 0.05); CVF (3.9 +/- 0.2)% vs (6.3 +/- 0.4)%, (P < 0.05) was
      decreased significantly, but LVDd, VWI and the systolic function was not chang
      significantly. The expression of GLUT4 mRNA and protein in sham operated with
      diabetes and diabetic with myocardial infarction descended significantly compared
      with sham operated group without diabete (P < 0.01). And in trimetazidine group,
      GLUT4 protein moderately increased (P < 0.05) compared with placebo group.
      CONCLUSION: Trimetazidine could improve the diastolic function of left
      ventricular. The expression of GLUT4 mRNA and protein in type 2 diabetes
      complicating with myocardial infarction decreased. Trimetazidine could improve
      the expression of GLUT4 mRNA and protein in diabetes complicating with myocardial
      infarction and inhibited myocardial fibrosis.

PMID- 19595177
TI  - [Association of CTLA-4 + 49A/G and CT60 gene polymorphism with type 1 diabetes
      and thyroid autoimmunity].
AB  - OBJECTIVE: To investigate the association of CTLA-4 + 49A/G and CT60 gene
      polymorphisms with type 1 diabetes (T1DM) and thyroid autoimmunity. Subjects
      Three hundred thirty-two T1DM patients and 476 controls were recruited in the
      study. METHOD: The CTLA-4 + 49 A/G and CT60 polymorphisms of CTLA-4 gene were
      analyzed by polymerase chain reaction restriction fragment length polymorphism
      (PCR-RFLP) method. Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody
      (TGAb) were determined by radioimmunoassay. Glutamic acid decarboxylase antibody
      (GADA) and protein tyrosine phosphatase antibody (IA-2A) were measured by
      radioligand immunoassay. RESULTS: (1) The CTLA-4 + 49 A/G polymorphism was
      significantly associated with T1DM complicated with thyroid autoimmunity (OR =
      2.43, P < 0.01) and with T1DM alone (OR = 1.66, P < 0.05). (2) The CTLA-4 CT60
      polymorphism was also significantly associated with T1DM complicated with thyroid
      autoimmunity (OR = 2.67, P < 0.01) and with T1DM alone (OR = 1.60, P = 0.02). (3)
      T1DM with thyroid autoimmunity was characterized by a significantly higher
      frequency of CTLA-4 CT60 GG genotype (77.8% vs 62.3%, P < 0.05) and GADA (77.8%
      vs 57.4%, P < 0.05) compared to the patients without thyroid antibodies.
      CONCLUSION: CTLA-4 + 49 A/G and CT60 gene polymorphism confers genetic
      susceptibility to type 1 diabetes, particularly in patients with thyroid
      autoimmunity.

PMID- 19595178
TI  - [Study on prevalence of latent autoimmune diabetes in adults and its relationship
      with metabolic syndrome].
AB  - OBJECTIVE: To investigate the prevalence, clinical features of latent autoimmune
      diabetes in adults (LADA) from phenotypic type 2 diabetic patients and the
      relationship between LADA and metabolic syndrome (MS). METHODS: Sera from 1711
      phenotypic type 2 diabetic patients were screened for glutamic acid decarboxylase
      antibody (GAD-Ab) and protein tyrosine phosphatase antibody (IA2-Ab) through
      radioligand assay. The prevalence of LADA and its relation with clinical features
      were analyzed. RESULTS: (1) The prevalence of LADA in phenotypic type 2 diabetic
      patients was 6.7% (115/1711), the positive frequency of GAD-Ab and IA2-Ab was
      6.0% and 2.4% respectively. (2) The prevalence of LADA from phenotypic type 2
      diabetic patients with a duration of diabetes less than 1 year which was much
      higher than that of patients with a duration over 1 year (10.4% vs 5.9%, P <
      0.01). (3) The prevalence of LADA was higher in patients with younger age at
      onset, lower body mass index and lower level of postprandial C peptide and
      without diabetes family history. (4) 51.3% of LADA patients were suffered from at
      least one kind of metabolic disorders besides hyperglycemia, 21.7% of them were
      with MS. The prevalence from high to low of those metabolic disorders were as
      follows: hypertension, dyslipidemia, overweight/obesity. CONCLUSION: (1) 6.7% of
      phenotypic type 2 diabetic patients were LADA, of whom early diagnosis of
      diabetic type should be made to guide clinical therapies. (2) More than 1/5
      patients with MS were found in LADA patients, indicating an overall screening and
      intervention of metabolic disorder factors is important in LADA patients.

PMID- 19595179
TI  - [Investigation of female chronic constipation: a multi-center cross-sectional
      clinical study].
AB  - OBJECTIVE: To analyze the characteristics of female chronic constipation (CC),
      contributing factors of severe constipation and the correlation between female CC
      and pelvic floor dysfunction (PFD) so as to provide references for the diagnosis
      and treatment of female CC. METHODS: Five hundred and sixty-one CC outpatients
      meeting Rome III criteria at clinics of gastroenterology from ten Beijing
      hospitals were recruited during March-May 2007. After data input and
      verification, formulated the standard of severe CC. RESULTS: The peak age of CC
      onset was 20 - 29 years in female patients while 60 - 69 years in male patients.
      F:M = 3.04:1. A wide range of CC symptoms were present and straining was the most
      common one (381, 76%). However, a significant difference between females and
      males was shown in defecation by manually pelvic floor supporting (female 26/69,
      38%, male 3/20, 15% in manual assisted defecation, P < 0.05) and urinary
      incontinence when coughing (female 95/422, 22.5%, male 13/139, 9.4%, P < 0.01).
      Severity of CC, its manifestations and pelvic floor dysfunction were closely
      correlated with frequencies of pregnancy and delivery. CONCLUSION: Owing to
      anatomic features of female pelvic floor and physiological nature of pregnancy
      and delivery, the early onset of CC in female patients should attract sufficient
      attention of multi-disciplinary clinicians.

PMID- 19595180
TI  - [Screening and identification analysis of serum protein biomarkers in
      nephroblastoma].
AB  - OBJECTIVE: To screen and characterize the serum protein biomarkers in
      nephroblastoma so as to establish the proteins as the specific serum biomarkers
      for diagnosis and prognosis monitoring. METHODS: The differential protein peaks
      were located by detecting serum samples of preoperative and postoperative
      patients and normal children using the SELDI-TOF MS technology. After
      purification, the differential proteins were further analyzed by LC-MS/MS and the
      protein sequences searched in database. RESULTS: Two peaks with m/z of 6455.5 and
      6984.4 were selected as potential biomarkers. They were weakly expressed in
      nephroblastoma (intensity: 1029 +/- 364, 297 +/- 126) but highly expressed in
      normal individuals (2108 +/- 837, 753 +/- 226); another peak with m/z of 9190.8
      was weakly expressed in preoperative sera (283 +/- 154) but highly expressed in
      serum samples of postoperative patients and normal children (5974 +/- 657, 6231
      +/- 519). The protein at 6455.5 and 9190.8 were identified as apolipoprotein C
      III and haptoglobin respectively. CONCLUSION: The detection of differentially
      expressed apolipoprotein C-III and haptoglobin may have potential utilities for
      serum diagnosis, malignancy classification and prognosis monitoring of
      nephroblastoma and is worthy of further studies and applications.

PMID- 19595182
TI  - [Comparison of clinicopathologic parameters and prognosis of gastric carcinoma
      between different phases].
AB  - OBJECTIVE: To compare the clinicopathologic parameters of gastric carcinoma
      between different phases and to investigate the prognostic factors for gastric
      carcinoma. METHODS: A total of 1016 consecutive gastric cancer patients were
      divided into two groups according to operating date, phase I (1994 - 1996) and
      phase II (2000 - 2006). The clinicopathologic parameters and prognosis were
      compared between the two phases. The prognostic factors were analyzed and
      compared. RESULTS: There were significant differences in the constituent ratio of
      male and female patients, the proportions of early gastric carcinoma, different
      TNM staged patients, specialized operation and adjuvant chemotherapy (all P <
      0.05), but no significant differences in tumor location, peritoneal spread, lymph
      node metastasis and radical resection between the two phases. The overall 5-year
      survival rate and 5-year survival rate after curative resection were 48.1% and
      61.5% respectively within phase II, significantly higher than 32.8% and 42.4%
      within phase I (all P < 0.01). Stratification analysis revealed that the survival
      rates of patients with curative resection, lymph node metastasis or not, advanced
      disease, different TNM stages, specialized operation, without adjuvant
      chemotherapy within phase II, were significantly higher than those within phase I
      (all P < 0.01). Multivariant regression analysis revealed that Borrmann type,
      histological type, depth of invasion, lymph node metastasis, curative resection,
      adjuvant chemotherapy and different phase were independent prognostic factors for
      gastric carcinoma. CONCLUSION: The therapeutic efficacy of gastric carcinoma
      within phase II was improved greatly as a result of elevated diagnostic rate of
      early gastric cancer, standardized radical operation and adjuvant chemotherapy.
      Gastric carcinoma within phase II was improved highly. It was elevated diagnostic
      rate of early gastric cancer, standardized radical operation, and adjuvant
      chemotherapy that contribute to such improvement.

PMID- 19595183
TI  - [Urological complications in 1223 kidney transplants].
AB  - OBJECTIVE: To review retrospectively the urological complications in 1 223 kidney
      transplants. METHODS: A total of 1 223 kidney transplants were divided into
      ureteroneocystostomy group (n = 948) and ureteroureterostomy group (n = 275)
      according to the methods of urinary tract reconstruction. The incidence and
      management of urological complications such as urinary fistula, obstruction of
      ureter, vesicoureteral reflux (VUR) and urinary tract infection (UTI) were
      summarized respectively. RESULTS: Overall, urological complications were
      encountered in 217 (17.7%) cases, including 43 cases of urinary fistula (3.5%),
      35 obstruction of ureter (2.9%), 14 VUR (1.1%) and 125 UTI (10.2%). Urinary
      fistula was 39 (4.1%) cases and 4 cases (1.5%) (P < 0.05), obstruction of ureter
      22 (2.3%) & 13 (4.7%) (P < 0.05), VUR 14 (1.5%) & 0 (0%) (P < 0.05) and UTI 109
      (11.5%) & 16 (5.8%) (P < 0.01) in the ureteroneocystostomy group and
      ureteroureterostomy group respectively. Seventy patients underwent surgical
      treatment. The 3-year survival rate of graft with urological complications and
      without urological complications were 82.3% and 84.7% respectively. CONCLUSIONS:
      Ureteroureterostomy can decrease the incidence of urological complications after
      kidney transplantation. Most of urological complications require surgical
      interventions. The long-term graft survival is not affected by a correctly
      treated urological complication.

PMID- 19595184
TI  - [Expression of NK cells receptor NKG2D from peripheral blood in patients with
      primary hepatic carcinoma and its clinical significance].
AB  - OBJECTIVE: To investigate the expression of NK cells receptor NKG2D from
      peripheral blood in patients with primary hepatic carcinoma and the relationship
      between NKG2D expression and cytotoxicity of NK cells. METHODS: Flow cytometry
      was used to determine the number of NK cells and the expression of NK cells
      receptor NKG2D from peripheral blood in patients with primary hepatic carcinoma
      (20 cases), hepatitis B cirrhosis (23 cases), hepatitis B (20 cases) and healthy
      control (20 cases). The microplate reader was used to detect cytotoxicity of NK
      cells in all cases. RESULTS: Among killing rate of NK cell for K562 cell, the
      expression rate of NKG2D in NK cells, the number of NKG2D(+)NK cells, NKG2D
      expression level of NK cells and the number of NK cells, the liver cancer group
      [(25 +/- 7)%, 6%, 0.7 x 10(7)/L, 15, (1.1 +/- 0.6) x 10(8)/L] decreased
      significantly as compared with the healthy group [(63 +/- 7)%, 36%, 8.3 x
      10(7)/L, 116, (2.7 +/- 1.1) x 10(8)/L] and the hepatitis B group [(41 +/- 8)%,
      16%, 2.8 x 10(7)/L, 49, (1.9 +/- 1.1) x 10(8)/L] (P < 0.05); and there was a
      slight decrease as compared with the hepatitis B cirrhosis group [(29 +/- 10)%,
      7%, 0.6 x 10(7)/L, 29, (1.5 +/- 1.2) x 10(8)/L] (all P > 0.05 except NKG2D
      expression level of NK cells P < 0.05). The activity of NK cells showed a obvious
      positive correlation with the number of NK cell and the positive rate of NKG2D in
      NK cells, the number of NKG2D(+)NK cells and NKG2D expression level of NK cells
      (r = 0.657, 0.770, 0.927, 0.734, all P < 0.01). CONCLUSION: The cytotoxicity and
      the NKG2D expression of NK cells decreased significantly from peripheral blood in
      patients with primary hepatic carcinoma. The activity of NK cells was closely
      related to the NKG2D expression level of NK cells. Enhancing the NKG2D expression
      level of NK cell may provide a new idea for adoptive immunotherapy of primary
      hepatic carcinoma.

PMID- 19595185
TI  - [An analysis on prognostic factors of hilar cholangiocarcinoma].
AB  - OBJECTIVE: To investigate the influencing factors on the prognosis of hilar
      cholangiocarcinoma. METHODS: The clinical data were retrospectively analyzed in
      86 cases of hilar cholangiocarcinoma admitted into our hospital from Jan. 2004 to
      July. 2008. RESULTS: Of 86 cases with hilar cholangiocarcinoma, the mean survival
      time was 13.7 +/- 2.3 months, 1-year survival 57.3% and 3-year survival 29.7%.
      The mean survival time in patients with resection operation (19.4 +/- 2.2 months)
      was significantly longer than those with no operation (7.2 +/- 1.2 months) (P <
      0.05). The mean survival time in patients with non-vascular resection group (23.4
      +/- 2.1 months) was significantly longer than those with portal vein resection
      alone group (15.3 +/- 1.4 months) and hepatic artery resection group (9.3 +/- 0.9
      month) (P < 0.05). Cox regression analysis showed that staging, tumor diameter
      and operative were the dependent prognosis factors while pathologic type,
      vascular resection and age not the dependent prognosis factors. CONCLUSION: The
      prognosis of hilar cholangiocarcinoma correlates with operative approach,
      clinical stage and tumor diameter. A surgeon must be cautious to choose the
      surgical approach for treatment.

PMID- 19595186
TI  - [Laparoscopic radical resection for gallbladder carcinoma].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic radical
      resection of gallbladder carcinoma. METHODS: The clinical feature, pathological
      stage, surgical procedure, postoperative recovery and follow-up results of 4
      patients undergoing laparoscopic radical resection of gallbladder carcinoma were
      retrospectively analyzed. RESULTS: A total of 4 cases were successfully
      performed. No operative deaths and complications happened. Two patients died of
      recurrence at 17 and 40 months respectively. There were no port-site and
      abdominal wall metastases occurred. CONCLUSION: Laparoscopic radical resection of
      gallbladder carcinoma is a safe and feasible procedure on basis of technique.
      Nonetheless prospective randomization study with a greater number of cases and a
      longer follow-up will be needed to evalut the long-term results of it.

PMID- 19595187
TI  - [Effect of Fluorouracil-inducible GM-CSF gene therapy regulated by Egr-1 promoter
      on chemotherapeutic hematopoietic damage of tumor-bearing mice].
AB  - OBJECTIVE: In order to explore the regulating effects of Egr-1 promoter sequences
      in transcriptional targeting by 5-fluorouracil (5-Fu) on the expression of
      hematopoietic growth factor genes. METHODS: The human GM-CSF cDNA and enhanced
      green fluorescent protein (EGFP) cDNA were linked together with IRES and then
      inserted into the expression vector pCIneo under control of the Egr-1 promoter
      (Egr-EG). The vector was transferred into human bone marrow stromal cell line
      HFCL by lipofectin(TM). The transfected cell clones (HFCL/EG) have been selected
      by the addition of G418. The cells are exposed to the clinically important
      anticancer agent 5-fluorouracil. The activity of EGFP in HFCL/EG cells was
      detected by flow cytometry. The post-chemotherapeutical expression of GM-CSF in
      HFCL/EG was confirmed with ELISA and Western blot and RT-PCR respectively. The
      effect of N-acetylcysteine (a free radical scavenger) on GM-CSF production post
      exposure to 5-Fu was examined. The HFCL/EG cells were transplanted intravenously
      into B16 melanoma in C. B-17 combined immunodeficient (SCID) mice. 5-Fu was given
      i.p. at Day 3. The white blood cell number in peripheral blood, the expression of
      EGFP and GM-CSF and in human stromal cell engrafted in recipient mice were
      detected by flow cytometry and RT-PCR respectively. Tumor volume in tumor-bearing
      mice was calculated. RESULTS: The results indicated that the activity of EGFP and
      the amounts of secreted GM-CSF in HFCL/EG cells exposed to 5-Fu increased as
      compared to non-5-Fu group with flow cytometry, RT-PCR and ELISA respectively. N
      acetylcysteine significantly decreased the concentration of GM-CSF in HFCL/EG
      cells treated with 5-FU. In contrast to two control groups, HFCL/EG (Egr-1
      regulatory element-derived expression of GM-CSF gene therapy) resulted in a
      proportionally obvious increase in the number of white blood cell after
      chemotherapy and no significant difference was found for tumor inhibition in
      recipient mice. CONCLUSIONS: These in vitro data provide an experimental basis
      for use of gene therapy of hematopoietic growth factor gene regulated by Egr-1
      promoter to protect hematopoiesis from 5-Fu-injury effects.

PMID- 19595199
TI  - [Correct understanding of the status and concepts on combined therapy of breast
      cancer].

PMID- 19595200
TI  - [An interpretation of the China edition of National Comprehensive Cancer Network
      (NCCN) clinical practice guideline for breast cancer].

PMID- 19595201
TI  - [Standardization of quantitative detection of human epidermal growth factor
      receptor 2 in invasive breast cancer: problems and solutions].

PMID- 19595202
TI  - [Axillary lymph nodes in breast cancer: anatomical basis and surgical
      management].

PMID- 19595203
TI  - [Comments on certain issues of breast-conserving surgery in breast cancer].

PMID- 19595204
TI  - [Development in the management of lymph node metastasis in breast cancer].

PMID- 19595205
TI  - [Several issues deserving more attention in medical imaging examination of breast
      cancer].

PMID- 19595206
TI  - [The necessity for establishing breast cancer census in women in China and the
      main points of practice].

PMID- 19595208
TI  - [Study on predictors of long term results for neo-adjuvant chemotherapy in
      locally advanced breast cancer].
AB  - OBJECTIVE: To identify predictive markers of the long-term outcome for neo
      adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with
      intravenous vinorelbine (V) and epirubicin (E) combination regimen. METHODS: One
      hundred and nineteen patients with LABC were treated from September 2001 to May
      2006. All patients were diagnosed as invasive breast cancer by 14G core needle
      biopsy and treated with three cycles of VE regimen before the operation. The
      patients were subjected to surgery and subsequently were given other three cycles
      of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the
      clinical responses. Local-regional radiotherapy was applied to all patients after
      the chemotherapy and followed by hormone-therapy according to hormone receptor
      status. The impact of clinical, pathological, and immunohistochemical features on
      disease free survival (DFS) and overall survival (OS) was evaluated. RESULTS: All
      patients were evaluable for responses: clinical complete response was documented
      in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response.
      The pathological complete response was found in 22 cases (18.5%). Of the
      patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months
      (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%,
      respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67
      expression (P=0.045), no pathological complete response after NC (P=0.034) were
      associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and
      post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological
      complete response after NC (P=0.034) were associated with a shorter survival.
      CONCLUSION: Pathological response in primary tumor, pre-Ki-67 and post-Ki-67
      expression, pre-ER expression are important predictors of long-term outcome for
      LABC patients with three cycles of VE regimen before operation.

PMID- 19595207
TI  - [Clinical characteristics comparison between triple-negative and non-triple
      negative breast cancer].
AB  - OBJECTIVE: To compare the clinical characteristics of triple-negative (TN) breast
      cancer and non-triple-negative (NTN) breast cancer, enrich the information of TN
      patients, and provide evidences for individualized combined treatment. METHODS:
      The data of 408 cases received operation in the year of 2002 was enrolled in this
      study. TN patients were confirmed according to the immunohistochemical (IHC) test
      of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu. The clinical
      characteristics, recurrence, metastasis and survival were compared between the
      two groups. RESULTS: Seventy-seven patients (18.9%) were confirmed TN cases. The
      median follow-up was 64 months (range, 3-79 months). Of all the cases, 58
      occurred local recurrence or metastasis and 51 died, it was 19 and 12 in TN
      group. Compared with the NTN group, the TN patient tended to be younger and the
      tumor mass larger (P=0.015 and 0.011). However, axillary lymph nodes metastasis
      occurred more often in NTN patients than in TN patients (P=0.001). The rate of
      local recurrence and metastasis in TN group was significantly higher than in NTN
      group (P=0.005 and 0.025), and TN cases were more likely to develop lung
      metastasis than NTN patients (P<0.01). The 3-year and 5-year overall survival
      rate in TN group were significantly lower than in NTN group (86.4% vs. 93.4%,
      P=0.0205; 77.7% vs. 87.9%, P=0.0215). The 3-year and 5-year disease-free survival
      rate in TN group were also significantly lower than in NTN group (78.4% vs.
      92.4%, P=0.0038; 72.8% vs. 85.8%, P=0.0041). Tumor size, lymph node status and
      triple-negative were the most important factors influencing the prognosis on
      multivariate Cox regression analysis. CONCLUSIONS: TN breast cancer haa some
      specific clinical characteristics. The prognosis of TN patients is worse than
      that of NTN patients. Further study is needed to find individualized treatment
      for TN breast cancer patients.

PMID- 19595209
TI  - [Clinical and pathological features of operable breast cancer in women over 65
      years].
AB  - OBJECTIVE: To study the clinical and pathological characteristics of operable
      breast cancer in women over 65 years. METHODS: The data of 95 patients treated
      from February 2003 to February 2005 were collected, and the clinicopathological
      characteristics were retrospectively analyzed. RESULTS: These 95 patients
      accounted for 26.1% of all female breast cancer patients registered in our
      hospital in the mean time. Local advanced breast cancer accounted for 74.5% of
      the patients. The median time from symptom presentation to treatment seeking was
      1.2 years. Curative resection was performed in 96 breasts of 94 patients, 71
      patients received chemotherapy and 67 received endocrine therapy. Sixty-four
      cases (67.3%) were confirmed invasive ductal carcinoma. Positive expression of
      estrogen or progesterone receptor was found in 65 cases (68.4%); overexpression
      of C-erbB-2 was found in 23.5% of the patients and low level expression of Ki-67
      (<30%) was found in 54.1% of the cases, respectively. The 3-year overall survival
      rate and disease free survival rate was 87.4% and 71.4%, respectively.
      CONCLUSIONS: Of the breast cancer in aged women, most are local advanced breast
      cancer. Breast cancer in the elderly women has distinctive clinicopathological
      characteristics. Less radical surgery combined with adjuvant chemotherapy and(or)
      endocrine therapy is feasible treatment.

PMID- 19595210
TI  - [Evaluation of angiogenesis in the tumorigenesis and progression of breast
      cancer].
AB  - OBJECTIVES: To investigate the expression of CD34, vascular endothelial growth
      factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical
      hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the
      correlation between angiogenesis abnormality and the tumor progression. METHODS:
      One hundred and sixty cases of resected tissues from breast cancer patients were
      enrolled in the study and were divided into 5 groups: 30 cases as normal
      controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with
      intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma.
      The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were
      determined with immunohistochemical techniques. The micro vascular density (MVD)
      in those tissues was determined with the expression of CD34. RESULTS: The
      expression level of CD34, VEGF and Flk-1/KDR were different among the groups,
      with the highest expression in the infiltrating ductal carcinoma group. With the
      progression of breast cancer, the major indexes showed no significant changes in
      the early stage of progression, but the expression of VEGF and Flk-1/KDR
      increased significantly from AH stage. Meanwhile, the MVD increased in the same
      way. There was significant difference between AH and intraductal carcinoma group
      in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05).
      CONCLUSIONS: Abnormality in angiogenesis may be an early event in the
      tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be
      the initiating factor of angiogenesis in the process of breast hyperplasia-AH
      breast cancer, it could be the molecular target of early diagnosis and treatment.

PMID- 19595211
TI  - [Study on the application of value of digital medical technology in the operation
      on primary liver cancer].
AB  - OBJECTIVE: To study the clinical application of digital medical in the operation
      on primary liver cancer. METHODS: The patients (n=11) with primary hepatic
      carcinoma treated between February and July 2008, including 9 cases of
      hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma, were scanned
      using 64 slices helicon computerized tomography (CT) and the datasets was
      collected. Segment and three-dimensional (3D) reconstruction of the CT image was
      carried out by the medical image processing system which was developed. And the
      3D moulds were imported to the FreeForm Modeling System for smoothing. Then the
      hepatectomy in treatment of hepatoma and implanting of catheter were simulated
      with the force-feedback equipment (PHANToM). Finally, 3D models and results of
      simulation surgery were used for choosing mode of operation and comparing with
      the findings during the operation. RESULTS: The reconstructed models were true to
      life, and their spatial disposition and correlation were shown clearly; Blood
      supply of primary liver cancer could be seen easily. In the simulation surgery
      system, the process of virtual partial hepatectomy and implanting of catheter
      using simulation scalpel and catheter on 3D moulds with PHANToM was consistent
      with the clinical course of surgery. Life-like could be felt and power feeling
      can be touched during simulation operation. CONCLUSIONS: Digital medical
      benefited knowing the relationship between primary liver cancer and the
      intrahepatic pipe. It gave an advantage to complete primary liver cancer
      resection with more liver volume remained. It can improve the surgical effect and
      decrease the surgical risk and reduce the complication through demonstrating
      visualized operation before surgery.

PMID- 19595212
TI  - [A clinical study of bile cultures and antibiotic susceptibility test in the
      patients with operation on biliary tract].
AB  - OBJECTIVE: To illustrate the bacteriology and their susceptibility to antibiotics
      in patients with biliary tract diseases and provide information for antibiotic
      choices. METHODS: The bile specimens were cultured and pathogens' susceptibility
      to antibiotics was obtained intraoperatively from 195 patients undergoing
      operations on biliary tract and 24 healthy liver donors from June 2007 to March
      2008. RESULTS: Among 195 bile specimens collected from the patients
      intraoperatively, 44 ones were found bacterial growth by culture (22.6%), in
      which 11 ones were mixed infections (25.0%). Fifty-five bacterial strains
      belonging to 16 species were identified from these bile specimens. They included
      34 Gram negative strains (61.8%), 19 Gram positive strains (34.6%) and 2 fungal
      strains (3.6%). The commonest pathogens were Escherichia coli (27.3%),
      Enterobacter cloacae (12.7%), Enterococcus faecalis (12.7%) and Enterococcus
      faecium (10.9%). Among 24 bile specimens collected from the healthy liver donors,
      one was found Escherichia coli growth by culture (4.2%). The results of
      susceptibility test showed that the resistant rates of Gram negative strains to
      Meropenem was 2.8%, followed by Imipenem (5.6%), Sulperazone (22.8%) and Amikacin
      (28.7%). In this study Gram negative strains were highly resistant to
      Penicillins, Quinolones, some third generation Cephalosporins and so on (>50.0%).
      None of Gram positive strains were resistant to Vancomycin and Teicoplanin. They
      were highly resistant to Penicillins, Quinolones, Clindamycin and so on (>40.0%).
      CONCLUSIONS: (1) Gram negative strains remain the commonest pathogens in biliary
      tract infection in Renji Hospital and the commonest pathogen is Escherichia coli.
      The infection of enterococcus is going up. The mixed infection cases happen
      mostly in acute biliary infection. (2) To treat biliary infection the broad
      spectrum antibiotics which are effective to Escherichia coli are optimal choices.
      Ceftazidime or Ciprofloxacin may be used in mild biliary infection. Sulperazone
      or Amikacin may be used in severe biliary infection. Imipenem and Vancomycins may
      be used as second choice to treat the infection which other drugs are ineffective
      to.

PMID- 19595213
TI  - [Staged total cavopulmonary connection for complex congenital heart diseases].
AB  - OBJECTIVE: To review the experience of staged total cavopulmonary connection
      (TCPC) in complex congenital heart diseases. METHODS: From June 1998 to March
      2008, 22 patients underwent staged TCPC for complex congenital heart diseases.
      Among them, 9 were univentricular and pulmonary artery valve stenosis; 3 were
      univentricular and pulmonary artery atresia; 1 was transposition of great
      arteries, crisscross heart and pulmonary artery valve stenosis; 1 was complete
      atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery
      atresia and atrioventricular valvular regurgitation; 1 was complete
      atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery
      valve stenosis and atrioventricular valvular regurgitation after Glenn procedure;
      1 was mirror image dextrocardia, single ventricle, pulmonary artery atresia,
      major aortopulmonary collateral arteries (MAPCAs) and right pulmonary
      arteriovenous fistula after Glenn procedure; 4 were tricuspid atresia and
      pulmonary artery valve stenosis; 1 was tricuspid atresia and pulmonary atresia; 1
      was mirror image dextrocardia, double-outlet of right ventricle, left ventricular
      hypoplasia, pulmonary artery valve stenosis, tricuspid incompetence, and MAPCAs.
      Among them, 5 patients received systemic-to-pulmonary artery shunt, bidirectional
      Glenn procedure and TCPC. Seventeen patients received bidirectional Glenn
      procedure, the mean age was (5.9+/-4.4) years old. Pulmonary artery pressure pre
      Glenn procedure was 17 to 20 mm Hg (1 mm Hg=0.133 kPa). Atrioventricular valve
      incompetence in 3 patients. Nakata index was less than 200 mm2/m2 in 4 patients
      before the first stage operation. The age of TCPC procedure was (9.6+/-4.9) years
      old, the interval time was (3.7+/-1.2) years. RESULTS: There was one in-hospital
      death, the mortality was 4.5%. The patient with univentricular and pulmonary
      atresia, received systemic-to-pulmonary artery shunt, bidirectional Glenn
      procedure and TCPC and died of pneumorrhagia. Other patients were recovered well,
      postoperative central venous pressure was 12 to 18 mm Hg, percutaneous oxygen
      saturation was 90% to 96%. The cardiac function were in NYHA class I to II.
      CONCLUSIONS: The staged TCPC was a good procedure in high-risk Fontan candidates.
      The results were satisfactory for those patients. This staged strategy may extend
      the operative indications for the Fontan procedure.

PMID- 19595214
TI  - [Intraoperative treatment for atrial fibrillation using bi-polar radiofrequency
      ablation system: a clinical report of 91 cases].
AB  - OBJECTIVE: To observe the short and mid-term therapeutic effects of Bi-polar
      ablation systems for intraoperative treatment of atrial fibrillation (AF).
      METHODS: From March 2005 to January 2007, 91 patients received intraoperative
      treatment of atrial fibrillation with Bi-polar ablation systems, including 5
      cases of paroxysmal atrial fibrillation and 86 persistent/permanent cases. The
      main concomitant heart diseases were rheumatic mitral valve diseases. Atricure
      Dry Ablation System was used for 37 cases and Cardioblate Irrigated Ablation
      System for 54 cases. The ablation lesion patterns included Cox-maze III, Modified
      Cox Mini-maze and Left-sided Maze. RESULTS: Mean ablation time was (14.1+/-6.7)
      min. No ablation-related complications occurred. Three patients died
      perioperatively. Two patients had permanent pacemaker implantation 3 months after
      operation. One case suffered from stroke and lower limb thrombosis 2.5 years
      after operation. Follow-up lasted for 6 to 29 months. The none-AF rhythm were
      62.5%, 85.2%, 79.0% and 74.5% at discharge, 3 months, 6 months, and>or=12 months
      respectively. Compared to Uni-polar Ablation therapy group, the restoration of
      sinus rhythm in Bi-polar group were significantly higher at 6 months and>or=12
      months postoperatively. The latest follow-up results indicated that 100% of
      preoperative paroxysmal atrial fibrillation patients restored sinus rhythm and
      75.3% of persistent/permanent patients were free from atrial fibrillation. The
      none-AF rhythm of Atricure group (81.1%) showed no difference from the
      Cardioblate (77.5%). Meanwhile there were no significant differences among the
      three ablation lesion groups. CONCLUSION: Intraoperative radiofrequency ablation
      with Bi-polar systems is a feasible, safe and highly effective surgical option
      compared to the Uni-polar ablation technique.

PMID- 19595215
TI  - [The surgical separation of pygopagus conjoined twins].
AB  - OBJECTIVE: To explore the program of preoperative evaluation, preoperative
      preparation and separation operation of pygopagus conjoined twins. METHODS:
      Clinical data of one case of pygopagus (male, gestational age 37 weeks, uterine
      incision delivery, 3.5 months old; twins of triplets; total body weight 8.0 kg.
      The twins have self-governed extremities, anus, penis. Four limbs can move
      independently). Separated successfully were analyzed. The auxiliary examination
      of X-rays, MRI, ultrasound, CT and 3D reconstruction, sensory evoked potential
      showed that there were process hypoplasia and lamina bifid of lumbosacral
      vertebrae below L3. Dural sac connected below L3 and conus medullaris located at
      L3. There were no conjunction of spinal cord and cauda equine. The decision of
      direct suture of dural sac was made by preoperative evaluation through
      measurement of circumference and area of conjoined dural sac. The separation
      surgery program was decided through team debate and sham operation. Separation
      operation was performed under the general anaesthesia. Crossing V-shaped skin
      flap was used to cover the wound surface. The dura of conjoined twins were
      sutured directly. The tension of skin flap was normal postoperative with
      continuing negative pressure drainage under the flap and pressure sterilized
      dressing. RESULTS: Successful separation of pygopagus conjoined twins was
      achieved. Lower extremities movements of separated twins were normal 6 h after
      operation. The drainage was removed 1 day postoperative, blood supplies of skin
      flap were normal. There were no complications of infection, cerebrospinal fluid
      leakage and neurological deficit. The healing of the skin flap was good. With 6
      months follow-up, the growth and neurological function were normal. CONCLUSION:
      Consummate preoperative preparation, accurate preoperative investigations,
      meticulous operative management, careful postoperative administration and good
      team cooperation are the keys to successful separation of pygopagus conjoined
      twins.

PMID- 19595217
TI  - [The clinical observation of bipolar transurethral plasma kinetic resection of
      prostate for high risk benign prostate hyperplasia].
AB  - OBJECTIVE: To evaluate therapeutic effect and reliability of bipolar
      transurethral plasma kinetic prostatectomy (TUPKP) for high risk level benign
      prostatic hyperplasia (BPH). METHODS: A total of 230 cases of high risk of BPH
      were treated with TUPKP. Among them, 132 cases with the residual urine of 40 to
      420 ml had accepted long term but inefficient medical therapy, 98 cases were
      suffered with repeating acute urinary retention. One hundred and seventy-three
      cases with the functional capacity>4 MET were performed the standard
      transurethral resection of the prostate (TURP), the other 57 cases with the
      functional capacity<4 MET were accepted the minimally invasive TURP. Among them
      12 cases complicated with bladder stones accepted Ho: YAG lithotripsy priory. The
      international prostate symptom score (IPSS), The maximal urinary flow rate (Qmax)
      and residual urine of the 2 groups before and after operation were analyzed.
      RESULTS: There was no transurethral resection syndrome occurred in both groups.
      After 3 to 12 months of follow-up postoperatively, the IPSS of the two groups
      were reduced from (21.9+/-5.7) and (23.7+/-5.0) to (4.4+/-2.3) and (5.5+/-2.4),
      residual urine were reduced from (61.8+/-18.4) ml and (103.9+/-77.3) ml to
      (13.0+/-6.2) ml and (15.8+/-6.1) ml, respectively. The Qmax was increased from
      (5.7+/-3.0) ml/s and (4.8+/-2.8) ml/s to (20.9+/-6.3) ml/s and (16.8+/-3.9) ml/s,
      there existed significant differences (P<0.01). However the IPSS, Qmax and
      residual urine of the standard group had progressed more obviously than the
      minimally invasive TURP group (P<0.05). CONCLUSIONS: It is safe and effective to
      use TUPKP for treating high risk patients of BPH with classic TURP and minimally
      invasive TURP according to different functional capacity. When the functional
      capacity is more than 4 MET, the standard procedures is preferred.

PMID- 19595216
TI  - [Clinical research for reason analysis of posterior cruciate ligament
      reconstruction revision].
AB  - OBJECTIVES: To study and analyze the clinical factors contributing to the failure
      of primary posterior cruciate ligament (PCL) reconstruction and to guide our
      clinical treatment. METHODS: From November 2001 to May 2007, 8 patients underwent
      PCL reconstruction revision because of pathological instability after primary PCL
      reconstruction. And the clinical failure factors of the primary reconstruction
      were analyzed. RESULTS: One case was reconstructed with bone-patellar tendon-bone
      (B-T-B) autografts, 7 cases with hamstring tendon autograft. The most probable
      causes of failure were improper graft placement in 7 cases (both femoral bone
      tunnels were behind the predicted one and tibial tunnels were in front of the
      predicted one). The reconstructed PCL in 4 cases ruptured absolutely and had been
      absorbed. Three cases had obviously loosen but still partly linked reconstructed
      ligament. These 8 cases all received primary PCL revision reconstruction. Among
      them, 6 cases were reconstructed with autograft (using a single-bundle quadruple
      hamstring graft in 3 cases, double-bundle quadruple hamstring graft in 1 case,
      single-bundle B-T-B autograft in 2 case), and 2 cases were reconstructed with
      allograft (using a single-bundle and a double-bundle B-T-B allograft
      reconstruction). CONCLUSIONS: Incorrect bone tunnel placement is the major factor
      contributing to the surgical failure in many reasons for the failure of PCL
      reconstruction. So, it might be suggested that there is a great need for a more
      precise anatomical bone tunnel placement.

PMID- 19595218
TI  - [Upper limbs motor maps in cortex and plasticity after the anatomical
      hemispherectomy].
AB  - OBJECTIVE: To locate motor functional area of patients who undergone modified
      anatomical hemispherectomy in order to analysis the plasticity of upper limbs
      motor. METHODS: The patients who undergone modified anatomical hemispherectomy
      were performed BOLD sequences, to locate functional cortical areas in their
      residual brain. RESULTS: 6 patients have performed examination of BOLD sequences
      by 3.0-T MRI.5 of them obtained contralateral upper limb motor areas in their
      residual brain, and 3 of them obtained ipsilateral and contralateral upper limb
      motor area map in cortex. The ipsilateral upper limb motor areas in the M1, SMA
      and posterior parietal cortex. CONCLUSIONS: The patients who undergone modified
      anatomical hemispherectomy is an excellent model to investigate mechanism of
      plasticity in the developing brain. Functional magnetic resonance (fMRI) provided
      fine spatial detail of brain responses, would describe the motor functional area
      of cortical maps. These patients exist ipsilateral motor areas in their residual
      mono hemisphere. The study indicated there maybe have somewhat extent of
      correlation between the surgical procedure and the outcome of neuroplasticity.

PMID- 19595219
TI  - [Some aspects about carotid endarterectomy].

PMID- 19595221
TI  - [The strategy of management for bilateral carotid atherosclerotic stenosis].
AB  - OBJECTIVE: To evaluate the indication, time and strategy of surgery for patients
      with bilateral carotid atherosclerotic stenosis. METHODS: Seventy-four patients
      with bilateral carotid atherosclecrotic stenosis were admitted to our hospital
      from February 1987 to December 2007. In 34 patients who presented with unilateral
      symptoms and underwent ipsilateral carotid endarterectomy (CEA), contralateral
      CEA or carotid artery stenting (CAS) was performed in 8 because of severe
      stenosis (> 70%) or unstable plaque. Thirty-eight patients presented with
      bilateral symptoms. Among them, 15 underwent CEA on both sides, 3 were performed
      CEA on one side and CAS on the other side, while 20 underwent unilateral CEA
      only. In 2 asymptomatic patients, CEA was also performed. RESULTS: Ninety-three
      cases of CEA were performed in 74 patients. Sixty-eight patients were uneventful
      after operation. Neurological deficits deteriorated in 2 patients. Four patients
      developed cardiac ischemia, cerebral hemorrhage and hoarseness respectively.
      Sixty-seven patients were followed-up for 4.9 years. No cerebral ischemia
      relevant to operated carotid artery developed in 63 patients. CONCLUSIONS: If the
      indication is obvious, CEA should be performed no matter how contralateral
      carotid artery is. The strategy of therapy is individual. Whether using shunt
      depends on intra-operative monitoring.

PMID- 19595222
TI  - [Clinical analysis of microsurgical carotid endarterectomy for carotid stenosis
      and occlusion].
AB  - OBJECTIVE: To evaluate the clinical effects of carotid endarterectomy for carotid
      stenosis and occlusion. METHODS: From August 2005 to November 2008 moderate and
      severe carotid stenosis or occlusion were found in 16 patients by Doppler
      ultrasonography (DUS), MRA, CTA, DSA. The stenosis degree ranged from 60% to 99%
      in 14 patients and complete occlusion in 2 patients. Twelve patients underwent
      standard carotid endarterectomy (sCEA) in whom 2 patients were placed carotid
      shunt and 1 patient underwent carotid patch angioplasty. Four patients underwent
      eversion carotid endarterectomy (eCEA). All operations were performed by
      microscope. RESULTS: There was no stroke, transient ischemic attack and mortality
      perioperatively and during follow-up from 1 month to 3 years. The ICA flow
      detected by follow-up duplex scan and MRA was unobstructed. The primary cerebral
      ischemic symptoms were obviously improved or disappeared after operation. The
      postoperative complications included one case of upper gastrointestinal
      hemorrhage and one case of hoarseness and bucking, which disappeared after
      medical treatment. CONCLUSIONS: CEA is an effective way for treating carotid
      stenosis. Different operative methods and techniques deal with different carotid
      lesions to achieve better effect. Microsurgical technique is useful for exposure
      of high ICA bifurcation and avoid effectively cranial nerve injury and other
      complications.

PMID- 19595223
TI  - [Effect of different duration of clopidogrel pretreatment on platelet activation
      in patients undergoing stenting].
AB  - OBJECTIVE: To investigate the effect of two clopidogrel pretreatment duration on
      platelet activation in patients undergoing stenting. METHODS: From July 2006 to
      December 2007 40 elective carotid or vertebral artery stenting patients were
      assigned into two groups: Group A (n = 24) initiated clopidogrel (75 mg/d) > or =
      5 d before stenting; group B (n = 16) initiated 3 - 4 days. Platelet-monocyte
      aggregates and fibrinogen receptors analyzed by flow cytometric, and platelet
      aggregation tests using optical aggregometry, as well as serum soluble CD40
      ligand quantified by enzyme-linked immunosorbent assay were assessed in
      peripheral blood samples obtained immediately before and at 0.5, 18 h and 6 d
      after stenting. RESULTS: Platelet-monocyte aggregates, fibrinogen receptors and
      serum soluble CD40 ligand were higher in group B than in group A (14.59% vs
      8.70%, P = 0.012; 4.87% vs 2.42%, P = 0.024; 5.79 microg/L vs 2.64 microg/L, P =
      0.020) at 18 h after stenting. Serum soluble CD40 ligand was higher in group B
      than in group A (0.49 microg/L vs 0.31 microg/L, P = 0.033) at 0.5 h after
      stenting. CONCLUSIONS: Premedication before stenting with clopidogrel 75 mg/d
      merely 3 - 4 d may be insufficient to achieve adequate platelet inhibition,
      whereas clopidogrel initiated at least 5 d could obtain preferable clinical
      antiplatelet efficacy.

PMID- 19595224
TI  - [Carotid angioplasty and stenting for stenosis of extracranial carotid artery].
AB  - OBJECTIVE: To evaluate the operation method and prevention from complications of
      extracranial carotid stenosis. METHODS: Three cases of carotid angioplasty and
      stenting for 271 patients with extracranial carotid stenosis were performed from
      October 2001 to June 2008. Before the operation, take Clopidogrel for 75 mg/d,
      Aspirin Delayed-Release Capsules for 100 200 mg/d, Simvastatin for 40 mg 1/night,
      for 5 - 10 d. Then treat continuous vein infusion Heparin 50 mg/d for 2 d. After
      the operation, continue antiplatelet and reduce blood fat therapy. RESULTS: All
      300 carotid stenting were successfully accomplished. DSA showed that the diameter
      of stenosed segment of carotid artery was markedly enlarged, and all clinical
      ischemia signs were improved remarkably. Seven cases suffered from complications
      in one week after operation and one died. Following up 3 - 24 months in 226
      patients, restenosis were found in 5 cases, among which 45 patients were
      evaluated at follow-up by means of ultrasonic examination for 36 months or so, no
      restenosis was found. No ischemic attack occurred at follow-up. CONCLUSIONS: The
      satisfactory effect and safety are achieved in the therapy of carotid stenosis by
      carotid angioplasty and stenting. Correct intraoperative treatment and skilled
      techniques are the key points of success.

PMID- 19595225
TI  - [Evaluation of cerebral hemodynamics in geriatric carotid stenosis pre- and post
      carotid artery stenting].
AB  - OBJECTIVES: To explore influencing factors of regional cerebral blood flow (rCBF)
      in geriatric carotid stenosis, and to analyze changes of rCBF and clinical
      symptoms after carotid stenting. METHODS: During August 2005 and April 2008, 68
      geriatric patients of carotid stenosis having SPECT examination in our hospital
      were retrospectively studied, whose diagnosis was approved by angiography.
      Correlated rCBF was compared separately in different stenotic degrees of carotid
      stenosis, in unilateral or bilateral stenosis, accompanied with vertebrobasilar
      stenosis (VBS) or not, with collateral circulation or not, before and after
      carotid stenting. RESULTS: When patients of unilateral carotid stenosis were
      grouped by different clinical factors, cases of patients with reduced rCBF were
      compared using chi(2) test: the P value was 0.046 and 0.020 when comparing group
      of stenotic degree 90% - 99% with group 70% - 89% and group 50% - 69%; the P
      value was 0.927 between group accompanied with VBS and group without; the P value
      was 0.222 between group with collateral circulation and group without. When
      comparing reduced rCBF cases between unilateral and bilateral carotid stenosis,
      the P value was 0.046. After carotid stenting, 76% of patients had their rCBF
      improved, and also the scores of presenting symptoms evaluated by modified Rankin
      scale were elevated from 1.4 +/- 0.7 on admission to 0.4 +/- 0.3 postoperatively
      (P < 0.001). CONCLUSIONS: The research indicates that higher stenotic degree and
      bilateral carotid stenosis may cause rCBF decrease in geriatric carotid stenosis.
      Carotid stenting may improve rCBF and change clinical symptoms significantly.

PMID- 19595229
TI  - [Fluid therapy in critically ill patients].

PMID- 19595230
TI  - [Research of splenic function and appropriate choice of splenic operation].

PMID- 19595226
TI  - [Changes of nitric oxide and endothelin serum level after carotid balloon
      denudation or stent assisted angioplasty: an experimental and clinical
      observation].
AB  - OBJECTIVE: To observe the changes of nitric oxide (NO) and endothelin (ET) serum
      level in the Guangxi BA-MA minipigs whose carotid arteries were injured by
      balloon denudation and in the patients with carotid stent assisted angioplasty.
      METHODS: Twelve Guangxi BA-MA minipigs were chosen. High fat/cholesterol feeding
      and endovascular balloon denudation were used to create a carotid artery
      atherosclerotic stenosis animal model. Blood samples were collected from
      peripheral veins before starting the procedure, and again, at 2 and 3 weeks after
      the procedure, respectively. Serum NO and ET concentrations of blood samples were
      tested. Nineteen patients with carotid artery stenosis who underwent stent
      assisted angioplasty were randomly selected, and their serum NO and ET were
      tested using the same methods as above. RESULTS: In the animal group, there was a
      significant decrease of mean NO concentration at 2 weeks after carotid injury (t
      test, P < 0.05), however, no significant change of ET was observed. A very
      significant increase of ET was observed at 3 weeks after the procedure (t-test, P
      < 0.01). In the patient group, there were no significant differences among serum
      NO or ET concentration of peripheral vein blood before, immediately after, and 6
      h after the endovascular treatment. CONCLUSIONS: In this study, a decrease of NO
      concentration and an increase of ET concentration of peripheral vein blood are
      found in BA-MA minipigs after carotid arteries are injured by balloon denudation,
      which might be a cue for the formation of atherosclerosis. However, no
      significant changes are observed in this group of patients who underwent carotid
      angioplasty treatment. Therefore, further studies are needed.

PMID- 19595231
TI  - [Probing into indication of living-related liver transplantation for Wilson's
      disease].
AB  - OBJECTIVE: To probe into indication of living-related liver transplantation
      (LRLT) for Wilson's Disease. METHODS: From January 2001 to February 2007, thirty
      seven living-related liver transplants were performed. A retrospective analysis
      was carried on outcome of those patients. The indications for LRLT were acute
      hepatic failure in 3 patients and chronic advanced liver disease in 32 patients
      including 13 patients with Wilsonian neurological manifestations. Two patients
      presented with severe Wilsonian neurological manifestations even though their
      liver functions were stable. According to the scoring system for evaluation of
      the neurological impairment in Wilson disease based on neurological signs and
      functions (total score was 30), the pre-transplantation score of those patients
      with neurological manifestations was 15.9 +/- 4.3 (n = 15). RESULTS: Thirty-seven
      patients were followed up for 20 - 93 months. The survival rates of post
      transplant patients and grafts at 1, 3, and 5 year were 91.9%, 83.8%, 75.7%, and
      86.5%, 78.4%, 75.7%, respectively. Postoperative surgical complications occurred
      in 2 donors with bile leakage required drainage, in 2 recipients with hepatic
      thrombosis underwent retransplantation of cadaveric liver and in 1 recipient with
      hepatic stenosis required balloon dilatation. Neurological function was improved
      in all recipients and the score of posttransplantation at 6, 12, 18, 24, and 30
      month was 17.5 +/- 3.7 (n = 13); 21.0 +/- 4.3 (n = 12); 23.9 +/- 3.9 (n = 10);
      26.6 +/- 2.2 (n = 10) and 28.1 +/- 1.9 (n = 7) respectively. CONCLUSIONS:
      Patients with acute hepatic failure or patients with severe liver disease
      unresponsive to chelation treatment should be treated with LRLT. Early
      transplantation in patients with an unsatisfactory response medical treatment may
      prevent irreversible neurological deterioration even though their liver function
      is stable.

PMID- 19595232
TI  - [Application of abdominal packing in non-trauma patients with severe abdominal
      hemorrhage].
AB  - OBJECTIVE: To assess the efficacy and safety of damage control surgery with
      abdominal packing in non-trauma patients with severe abdominal hemorrhage.
      METHODS: A retrospective review of consecutive non-trauma patients who underwent
      abdominal packing to control severe abdominal hemorrhage between February 2002
      and February 2007 were performed. The demographics, physiological parameters,
      surgical indications and procedures, mortality, morbidity and volumes of
      resuscitation were retrieved. The observed mortality was compared to those
      calculated from the Physiological and Operative Severity Score for the
      Enumeration of Mortality and Morbidity (POSSUM) and Portsmouth Predictor Equation
      (P-POSSUM) scores. RESULTS: A total of 26 non-trauma patients were included in
      this study, with a mean age of (42.6 +/- 15.8) years (range, 18 - 72 years). The
      most common etiologies associated with the severe hemorrhage was necrotizing
      pancreatitis (11 cases), intestinal fistula (5 cases) and tumor (4 cases). Of the
      patients, 24 cases (92.4%) achieved hemostasis by simple packing, 1 achieved
      hemostasis by using packing and angiographic embolization, and the other one
      failed and died. The mean intra-operative blood loss during the initial procedure
      was 1253.8 ml. The physiological parameters which improved significantly after
      rewarming and resuscitation in ICU phase included: body temperature, systolic
      blood pressure, heart rate, arterial pH, base excess, hemoglobin, hematocrit,
      prothrombin time, and international normalized ratio. The mean duration of
      packing was 4.3 days. The mean length of SICU stay and hospital stay was 40.5 and
      67.4 days, respectively. Mortality rate predicted by POSSUM and P-POSSUM was
      77.7% and 63.4%, respectively. Seven patients (26.9%) died after operation,
      brought an observed mortality rate significantly lower than predicted (P = 0.001
      and 0.025, respectively). The most common complications included pneumonia
      (57.7%), bacteremia (50.0%), and re-bleeding (26.9%). CONCLUSIONS: Damage control
      laparotomy with packing is an effective procedure in the management of severe non
      trauma abdominal hemorrhage, it can prevent the aggravation of "lethal triad"
      characterized by hypothermia, coagulopathy and acidosis. Appropriate application
      of the technique in strictly selected patients can result in a lower mortality
      rate.

PMID- 19595233
TI  - [Long-term results of TIPS, TIPS with CVO and combined TIPS and portal azygous
      disconnection for the treatment of portal hypertension].
AB  - OBJECTIVE: To analyze the long-term results of TIPS, TIPS with coronary vein
      occlusion (CVO) and combined TIPS and portal azygous disconnection for the
      treatment of portal hypertension and variceal bleedings. METHODS: Three hundreds
      and fifty-eight patients with portal hypertension were admitted because of
      variceal bleeding from July 1993 to May 2008. All patients were divided into 3
      groups: 227 cases in group TIPS, 36 cases in TIPS and CVO group, 95 cases in
      combined TIPS and portal azygous disconnection group. The rates of successful
      operation, shunt patency, rebleeding, encephalopathy and survival were observed
      and compared by statistics methods. RESULTS: There were 349 cases (97.5%)
      underwent successful surgery and 9 cases with failure surgery. The rates of
      occluded shunts, encephalopathy, rebleeding, and death in early periods were
      2.5%, 31.8%, 4.7% and 9.0% respectively. The rate of encephalopathy and death in
      group with TIPS were higher than in group with combined TIPS and portal azygous
      disconnection (P < 0.01). The rate of encephalopathy and death were 41.2% and
      24.7% in 85 cases with emergency TIPS. During the follow-up 1 - 15 years, the
      rate of patency shunts in 12 and 24 months after operation was 74.0% and 48.1%
      respectively. The rate of 1-year patency shunts in group with combined TIPS and
      portal azygous disconnection was higher than in group with TIPS, TIPS and CVO (P
      < 0.01 and P < 0.05). The rebleeding in group with TIPS was higher than in group
      with combined TIPS and portal azygous disconnection (P < 0.01), and the survival
      rate in group with TIPS was lower than in group with TIPS and CVO, combined TIPS
      and portal azygous disconnection (P < 0.01 and P < 0.01). CONCLUSIONS: TIPS is an
      efficient therapy for portal hypertension with CVO, combined TIPS and portal
      azygous disconnection can improve the results of TIPS for portal hypertension.

PMID- 19595234
TI  - [Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases].
AB  - OBJECTIVE: To investigate the clinical features and treatment of multifocal
      papillary thyroid carcinoma (PTC). METHODS: A retrospective survey was carried
      out in 648 patients with PTC who underwent surgery from January 1997 to December
      2006. One hundred and sixty-eight cases of the patients presented with multiple
      tumor masses (> or = 2). The risk factors, including sex of the patients, age at
      diagnosis, family history of thyroid tumor, multiplicity and bilaterality of
      tumor, extra-thyroidal extension, lymph node involvement and other were analyzed
      between solitary PTC and multifocal PTC group. RESULTS: The mean age of the
      patients was 42 years (range, 14 - 78 years), included 49 male and 119 female.
      Tumor foci were found in both thyroid lobes in 117 cases (69.6%). Patients with
      multifocal PTC were characterized by a higher ratio of male (P = 0.004), family
      history of thyroid tumor (P = 0.031), neck lymph node metastasis (P = 0.008) and
      extra-thyroidal extension (P = 0.001). However, solitary PTC tended to be with a
      higher rate of benign goiters in pathologic examination. In multifocal PTC group,
      male, neck lymphadenectasis, > or = 3 tumor masses or bilaterality of tumor
      tended to presented with larger tumor, more neck lymph node metastasis and extra
      thyroidal extension; And a less malignant tumor in the cases detected with benign
      goiters in histological examination. By the end of 2007, 164 cases (97.6%)
      completed follow-up with a mean period of 46.1 months (range, 2 - 127 months), 5
      died in the meantime. One patient has been followed-up for 16 months for suspect
      of lung metastases by chest X-ray. Recurrence occurred in 8 patients and were re
      resected, 2 in remnant thyroid and 6 in neck lymph nodes. The overall 1-, 2-, 5-,
      and 10-year survival rate was 98.2%, 97.4%, 96.5% and 96.5%, respectively.
      American Joint Committee on Cancer (AJCC) stage was associated with prognosis
      significantly (chi(2) = 168.832, P = 0.000). CONCLUSIONS: Multifocus is one of
      the clinical features of PTC and is more malignant than solitary PTC. Total
      thyroidectomy with central compartment neck dissection could be standard
      treatment. Lateral nodal dissection is not necessary except for the cases with
      lymph node metastasis. AJCC stage is still the best prognostic factor.

PMID- 19595235
TI  - [Video-assisted thoracoscopic lobectomy for benign pulmonary diseases].
AB  - OBJECTIVE: To evaluate technique aspects of video-assisted thoracoscopic
      lobectomy for benign diseases. METHODS: Retrospective review of 24 patients with
      benign pulmonary disease underwent thoracoscopic lobectomy from September 2006 to
      September 2008. One patient had bilateral bronchiectasis received concurrent
      bilateral lobectomy. The patients included 11 males and 13 females with mean age
      of 49.0 years. Fifteen cases were diagnosed as benign diseases preoperatively
      consisted 10 bronchiectasis as the primary indication. The other 9 cases were
      pulmonary nodules pathologic diagnosed intra-operatively. Inflammation changes
      including dense plural adhesions, pulmonary artery adhesions and calcified lymph
      nodes were managed endoscopically. RESULTS: All 25 thoracoscopic procedures were
      completely with no conversion to thoracotomy. The mean operation time was (163 +/
      52) min, blood loss was (163 +/- 130) ml. There was no hospital death or major
      morbidity. Postoperative drainage was (5.8 +/- 2.8) d. No long-term complications
      were noticed during a mean follow-up of 7.3 months. CONCLUSION: Chronic
      inflammation induced adhesions is the key limiting factor for thoracoscopic
      lobectomy for benign diseases.

PMID- 19595236
TI  - [The early and middle-long term clinical results of surgical treatment for
      ventricular septal rupture].
AB  - OBJECTIVE: To explore the way of promoting the efficacy of surgical treatment for
      ventricular septal rupture (VSR) after acute myocardium infarction in terms of
      perioperative and long term survival. METHODS: The clinic data of 37 VSR cases
      underwent surgical treatment from October 1994 to October 2007 were analyzed
      retrospectively. There were 24 male and 13 female, and the age was (63.4 +/- 7.6)
      years old. The whole group was divided into the VSR repair plus revascularization
      group (group A, 26 cases) and simple VSR repair group (group B, 11 cases).
      RESULTS: There were 4 operative deaths in group A (15.4%), 7 deaths in group B
      (63.6%), P = 0.006. With the follow-up of (34.0 +/- 29.8) months ranged from 2 to
      103 months of the 26 operational survivors, there were 5 late deaths, of which 2
      deaths in group A and 3 deaths in group B. According to the Kaplan-Meier survival
      curve, the actuarial survival rate at 6 to 8 year was (64.3 +/- 21.0)% for group
      A and the actuarial survival rate at 4 year was (25.0 +/- 21.7)% for group B, P =
      0.011. Of the 21 mid-long term survivors, 17 cases were in NYHA class I to II and
      4 cases in NYHA class III to IV. There were 4 cases suffered from VSR recurrence.
      According to Logistic regression, the risk factors for the early death were not
      adoptive of revascularization, cardiogenic shock and emergency surgical
      procedure, while the risk factors for late death were not adoptive of
      revascularization and low cardiac output after the procedures. CONCLUSIONS: VSR
      repair plus revascularization could improve the perioperative and mid-long term
      survival for the surgical treatment of VSR. The appropriate timing and procedures
      of the surgical operation are very important to promote perioperative survival
      and to prevent VSR recurrence.

PMID- 19595237
TI  - [The prospective study project of 62 cases spinal cord injury].
AB  - OBJECTIVE: To rudiment analyze the different intervention factors affecting the
      spinal cord injury functional recovery initially through prospective study
      project. METHODS: Designed prospective study project without clinical treatment
      intervention and admitted 62 spinal cord injury cases into observation group from
      Dec 2006 to Dec 2007. The internalized standard included acute spinal cord injury
      within 1 week, aged from 18 to 65 years old without sexuality difference and
      diagnosed as type A injury: total spinal cord injury or type B injury: non-total
      spinal cord injury (without movement function below the injury plane) according
      to clinical physical examination and combined MRI or CT examination. All the 62
      cases were followed up. The spinal cord function were estimated at the time of
      arriving hospital, 1, 3, 6 months after injury during the following up time
      according to the American Spine Injury Association standard (Revised at 2000) and
      functional independence measure (FIM) score. The intervention factors affecting
      the spinal cord injury functional recovery were analyzed. RESULTS: Among the 62
      cases, male 60 cases and female 2 cases, aged from 18 to 41 years old, mean age
      24 years old, 29 cases can be classified into type A injury and 33 cases can be
      classified into type B injury. There was no significant difference (Index
      including sense ASIA, motor ASIA and FIM) between operation group and non
      operation group, namely conservatively composite treatment at all observation
      point in all type A injury cases (P > 0.05). There was significant difference
      (Index including sense ASIA, motor ASIA and FIM) between operation group and non
      operation group at all observation point in all type B injury cases (P < 0.05);
      And there was significant difference (Index including sense ASIA, motor ASIA and
      FIM) between operated in 8 hours (< or = 8 h) group and beyond 8 hours (> 8 h)
      group at all observation point in all type B operated cases (P < 0.05).
      CONCLUSIONS: Operation and operation time were of no significant value for type A
      injury (total spinal cord injury), but considering the nursing convenience and
      the need for spinal stabilities, operation decompression and internal fixation
      can be chosen; Operation decompression should be performed as soon as quickly for
      type B injury (non-total spinal cord injury) in order to get better functional
      recovery.

PMID- 19595246
TI  - [Children anesthesia: yesterday, today and tomorrow].

PMID- 19595238
TI  - [Biomechanical strength of bone cement impregnated with diphosphonate].
AB  - OBJECTIVE: To investigate the biomechanical strength of diphosphonate impregnated
      bone cement (DIBC). METHODS: DIBC specimens were manufactured and randomly
      assigned to the control groups and the DIBC groups. According to the
      corresponding ASTM/ISO standards, the static biomechanical strength and the
      fatigue limit were tested systematically. The particle size distribution of
      diphosphonate powder was analyzed with the laser light scattering method. The
      fatigue test results, given as number of cycles-to-failure, were analyzed using
      the linearized format of the two-parameter Weibull function. RESULTS: With the
      drug load increased, there was a slight increase in static biomechanical strength
      and a moderate decrease in fatigue limit, both with statistical significance.
      When immersed in PBS before the tests, the DIBC specimens presented an overall
      significant decrease of static biomechanical strength and fatigue limit. The
      profile of drug particle sizes presented a normal distribution. CONCLUSIONS: The
      adopted diphosphonate is a much homogeneous powder which contains particles with
      a low range of sizes. The impregnation of diphosphonate exerted no or less
      negative effect on the biomechanical strength of the acrylic bone cement, of
      which the static strength of DIBC is maintained high above the ASTM/ISO
      standards.

PMID- 19595247
TI  - [Optimal concentrations of sevoflurane and propofol for laryngeal mask airway
      insertion in Chinese boys of different ages].
AB  - OBJECTIVE: To investigate the optimal concentrations of sevoflurane and propofol
      for laryngeal mask airway (LMA) insertion in Chinese boys of different ages.
      METHODS: 200 boys with ASA status I weighting 7 - 53 kg undergoing inguinal
      operation were divided into 4 groups (n = 50) according to age: Group A (aged 7 m
      1 yr), Group B (1 - 3 yrs), Group C (4 - 6 yrs), and Group D (7 - 11 yrs). No
      premedication was given. General anesthesia was induced with propofol intravenous
      infusion at target effect-site concentration by target controlled infusion (TCI)
      using children Marsh model (Subgroups As, Bs, Cs, and Ds, 25 cases for each
      subgroup) or sevoflurane inhalation combined with 50% N2O (Subgroups Ap, Bp, Cp,
      and Dp, 25 cases for each subgroup) the optimal concentration was predetermined
      according to the modification of Dixon's up-and-down method. The size of LMA was
      determined according to the boy's weight and reverse technique was used to place
      LMA. The insertion conditions were noted as satisfactory when the jaw was
      relaxed, lash reflex disappeared, no coughing, gagging, swallowing, and
      laryngospasm was seen, and limb movement was minimal. RESULTS: The levels of
      ED(50) of P(ET)-sevoflurane for LMA insertion in Subgroups As, Bs, Cs, and Ds
      were 2.96% (95% CI 2.58% - 3.44%), 2.62% (95% CI 2.31% - 2.90%), 2.16% (95% CI
      1.97% - 2.33%), and 1.89% (95% CI 1.66% - 2.24%) respectively. The levels of
      ED(50) of target effect site concentration with propofol for LMA insertion in
      Subgroups Ap, Bp, Cp, and Dp were 4.74 microg/ml (95% CI 4.49 - 5.13 microg/ml),
      4.33 microg/ml (95% CI 4.07 - 4.62 microg/ml), 4.10 microg/ml (95% CI 3.90 - 4.31
      microg/ml), and 3.65 microg/ml (95% CI 3.24 - 3.98 microg/ml) respectively.
      CONCLUSION: The ED(50) level of P(ET)-sevoflurane or target effect site
      concentration with propofol for LMA insertion in Chinese boys decreases gradually
      along with the increase of age.

PMID- 19595248
TI  - [Effects of sevoflurane postconditioning on renal ischemia-reperfusion injury:
      experiment with rats].
AB  - OBJECTIVE: To investigate the protective effects of postconditioning with
      different concentrations of sevoflurane on renal ischemia-reperfusion (I/R)
      injury. METHODS: The following procedures were performed on 48 male SD rats to
      establish I/R models: the right kidney and ureter were resected, and the left
      renal arteries and veins were occluded by atraumatic clamps for 45 min and then
      the clamps were removed to provide reperfusion for 24 h. And the rats were
      randomly divided into 4 equal groups; I/R Group, S(1.2) Group inbreathing 1.2%
      sevoflurane simultaneously since the beginning of reperfusion for 2 h, S(1.8)
      Group inbreathing 1.8% sevoflurane simultaneously since the beginning of
      reperfusion for 2 h, and S(2.2) Group inbreathing 2.2% sevoflurane simultaneously
      since the beginning of reperfusion for 2 h. Another 12 rats underwent resection
      of the right kidney and ureter and exposure of the left renal arteries and veins
      only for 45 min. The rates were killed at the end of 24h reperfusion. Blood
      samples were taken for determination of serum creatinine (Cr) and blood urea
      nitrogen (BUN). The left kidneys were harvested to undergo microscopy to observe
      the percentage of pyknotic nuclei in cortical tubular cells. Immunohistochemistry
      was used to detect the expression of endothelial nitric oxide synthase (eNOS) and
      inducible nitric oxide synthase (iNOS) in the kidney. RESULTS: The necrotic rate
      of renal tubule of the Sham Group was significantly lower than those of the other
      4 groups (all P < 0.01), and the necrotic rates of renal tubule of the S(1.2),
      S(1.8), and S(2.2) Groups were all significantly lower than that of I/R Group
      (all P < 0.05). The levels of blood Cr and BUN, and the percentage of pyknotic
      nuclei in cortical tuber cells of I/R, S(1.2), S(1.8), and S(2.2) Groups were all
      significantly higher than those of Sham Group (all P < 0.05) and these indexes
      listed above of S(1.2), S(1.8), and S(2.2) Groups were all significantly lower
      than those of I/R Group (all P < 0.05). However, there were not significant
      differences in these indexes among S(1.2), S(1.8), and S(2.2) Groups (all P >
      0.05). The kidney eNOS and iNOS expression levels of I/R Group were both
      significantly higher than those of Sham Group (both P < 0.05), and the kidney
      eNOS and iNOS expression levels of S(1.8) Group were both significantly lower
      than those of I/R Group (both P < 0.05). CONCLUSION: Sevoflurane postconditioning
      attenuates the renal damage induced by I/R and down-regulates the eNOS and iNOS
      expression in kidney.Different concentrations do not show different effects.

PMID- 19595249
TI  - [Minimum alveolar concentration of sevoflurane for insertion of laryngeal mask
      airway in children].
AB  - OBJECTIVE: To investigate the minimum alveolar concentration (MAC) of sevoflurane
      required for insertion of laryngeal mask airway (LMA) in anesthetized children.
      METHODS: 27 children, aged 3-8, with an ASA physical status I or II, underwent
      elective surgery under general anesthesia induced by inhalation of 8% sevoflurane
      in oxygen. After loss of eyelash reflex, the designated end-tidal concentration
      of sevoflurane remained stable for at least 10 min, and then the LMA was
      inserted. Each target concentration at the time of insertion was predetermined by
      the Dixon up-and-down method (with 0.2% as a step size) starting at 2.0% end
      tidal concentration of sevoflurane. Successful insertion was defined as excellent
      inserting condition (fully relaxed jaw, no coughing, and no movement of the
      limbs, no breath holding, and no laryngospasm). RESULTS: The mean MAC of
      sevoflurane to achieve successful LMA insertion in 50% of children was (2.01 +/-
      0.19)%, and the ED(95) was 2.36% (95% CI 2.15% - 4.15%). CONCLUSION: LMA
      insertion can be safely accomplished without coughing, moving, or any other
      airway complications in 50% and 95% of children at 2.01% and 2.36% end-tidal
      concentrations of sevoflurane.

PMID- 19595250
TI  - [Effects of cardiopulmonary bypass on plasma pentraxin-3 level and the balance of
      Th1/Th2 function in children with congenital heart malformations].
AB  - OBJECTIVE: To investigate the effects of cardiopulmonary bypass (CPB) on plasma
      pentraxin-3 (PTX3) level and balance of Th1/Th2 function in children with
      congenital heart malformations. METHODS: 16 children with congenital heart
      malformations, 9 male and 7 female, aged 3 - 52 months, weighing 3.4 - 14.5
      kilograms, classified as II or III ASA grades, underwent operation under CPB.
      Blood samples were collected after anesthesia induction, 5 min and 30 min since
      beginning of CPB, and 5 min, 2 h, 4 h, 8 h, and 16 h after weaning from CPB.
      ELISA was used to examine the plasma concentrations of interferon (INF)-gamma,
      interleukin (IL)-4, and PTX3. The ratio of INF-gamma/IL-4 was calculated.
      RESULTS: The INF-gamma level began to increase significantly 5 min since CPB (P <
      0.05), peaked 5 min after weaning from CPB (P < 0.01), then gradually decreased,
      and returned to the level before CPB 16 h after the weaning from CPB (P > 0.05).
      The IL-4 level began to increase significantly 30 min since CPB (P < 0.01),
      peaked 2 h since CPB (P < 0.01), however, still not returned to the level before
      CPB 16 h after the weaning from CPB (P < 0.05). The PTX-3 level was significantly
      higher 30 min since CPB and 5 min and 2 h after the weaning from CPB (all P <
      0.01). The INF-gamma/IL-4 ratio was significantly higher 5 min and 30 min since
      CPB and 5 min after weaning from CPB (all P > 0.05). CONCLUSION: CPB can leads to
      elevation of plasma concentration of PTX3 and drift of Th1/Th2 function
      equilibrium, thus resulting in immunity disequilibrium.

PMID- 19595251
TI  - [Immune and inflammation confusion in severe sepsis and effects of bi
      immunomodulation therapy: a prospective, randomized, controlled clinical trial].
AB  - OBJECTIVE: To investigate the immune and inflammation confusion state in severe
      sepsis and the effects of two way immunomodulation therapy with continuous blood
      purification (CBP), thymosin alpha1, and combined therapy of CBP and thymosin
      alpha(1). METHODS: 91 Patients with severe sepsis aged > 18, with Marshall
      score>5. were randomly divided into 4 groups: CBP Group (n = 22) undergoing
      continuous renal replacement therapy (CRRT) or molecular adsorbents recirculating
      system (MARS) therapy once a day for 3 days in addition to classical Surviving
      Sepsis Campaign (SSC) therapy, Thymosin alpha(1) Group (n = 23) undergoing
      subcutaneous injection of thymosin alpha(1) 1.6 mg once a day for 7 days in
      addition to SSC therapy, Combined Therapy Group (n = 22) undergoing CBP combined
      with thymosin alpha(1) treatment in addition to SSC therapy, and SSC Group
      (treatment control group, n = 24) undergoing SSC therapy only. Peripheral blood
      samples were collected before treatment, and 3 and 7 days after the beginning of
      treatment (days 4 and 8) to detect the serum interleukin (IL)-6, IL-10, and tumor
      necrosis factor (TNF)-alpha. The levels of CD(14)(+) monocyte human leucocyte
      antigen (HLA)-DR and T lymphocytes were monitored. The mechanical ventilation
      time, ICU stay length, and mortality within 28 d and mortality within 90 d were
      observed. Ten healthy persons were used as healthy control group. RESULTS: Thirty
      four of the 91 patients died within 28 d with a mortality of 77.4% (Death Group)
      and other 57 patients were put in Survival Group. The levels of serum IL-6, IL
      10, and TNFalpha, and IL-6/IL-10 at different time points of both Death and
      Survival Groups were all significantly higher, and the HLA-DR level, and
      CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte numbers at different time points of
      both Death and Survival Groups were all significantly lower than those of the
      healthy controls (P < 0.05 or < 0.01). The levels of serum IL-6, IL-6/IL-10,
      TNFalpha, HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte at different
      time points of Death Group were all significantly higher than those of Survival
      Group (P < 0.05 or < 0.01). The CD(3)(+) T lymphocyte number on day 8 of Thymosin
      Group was significantly higher than that of SSC Group (all P < 0.05). The serum
      IL-6 and TNFalpha and IL-6/IL-10 were decreased, and HLA-DR, and CD(3)(+),
      CD(4)(+), and CD(8)(+) were increased significantly on day 8 in CBP and Combined
      Therapy Groups. The level of TNFalpha decreased, and the numbers of CD(3)(+) and
      CD(4)(+) T lymphocytes increased significantly on day 4 in Combined Therapy Group
      (P < 0.05 or P < 0.01). Compared with Thymosin Group, almost all the indexes of
      CBP and Combined Therapy Groups were improved, only the CD(3)(+) T lymphocyte
      level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased
      significantly in Combined Therapy Group (both P < 0.05). Compared with those of
      SSC Group, the mechanical ventilation time, length of ICU stay within 28 days,
      and 28 days mortality and 90 days mortality of the 3 treatment groups were all
      decreased, and there were statistical differences in the length of ICU stay of
      CBP Group and in the mechanical ventilation time and length of ICU stay within 28
      days of Combined Therapy Group (both P < 0.05). CONCLUSION: Systemic inflammatory
      response and immunodepression exist simultaneously in severe sepsis. Thymosin
      alpha(1) increases the cellular immunity, and CBP bi-modulates the immune
      turbulence, reduces the inflammatory mediators, and ameliorates the immune
      homeostasis. These 2 therapies also improve the clinical prognosis and the
      combination of both would be more effective.

PMID- 19595252
TI  - [Assessment of correction effect in relation to fulcrum bending flexibility in
      adult idiopathic scoliosis patients].
AB  - OBJECTIVE: To study the relationship between the fulcrum bending flexibility
      (FBF) and correction rate (CR) of adult idiopathic scoliosis, and to explore the
      ability of FBF to assess the correction effect in relation to fulcrum bending
      flexibility. METHODS: 69 patients with adult idiopathic scoliosis with structural
      curves at thoracic or lumbarthoracic segments, 16 males and 53 females, aged 26.5
      (19 - 53) were treated by pedicle screws instrumentation. Pre-operative standing
      and fulcrum bending films and postoperative standing X-ray film were taken. Cobb
      angle was measured. The data underwent regression analysis with the software SPSS
      10.0. RESULTS: A regression formula was established: CR = 0.213 + 0.768 x FBF
      with P < 0.01. CONCLUSION: A definite linear relation exists between the FBF and
      CR of adult idiopathic scoliosis. By using the formula in proper samples, the
      effects of new instrumentation or correction technique can be objectively
      assessed.

PMID- 19595253
TI  - [Memory monitoring in mild cognitive impairment].
AB  - OBJECTIVE: To explore the profile of changes of memory monitoring in patients
      with mild cognitive impairment (MCI). METHODS: Rey- auditory verbal learning test
      (AVLT) and feeling-of-knowing (FOK) test in episodic memory (EM) and semantic
      memory (SM) were conducted on 30 MCI patients, 17 males and 13 females, aged (66
      +/- 9), and 30 age, education level, word fluency test, and digit span-matched
      healthy persons as healthy control (HC) group. RESULTS: The EM impairment of the
      MCI group was (13.7 +/- 2.8), significantly higher than that of the HC group
      [(8.1 +/- 2.0), P < 0.01], but the SM impairment of the MCI group was (5.4 +/-
      1.4), not significantly different from that of the HC group [(5.0 +/- 1.4), P >
      0.05]. The EM-FOK of the MCI patients with correct judgment and false recognition
      was (41.8 +/- 13.2)%, significantly higher than that of the HC group [(28.1 +/-
      11.6)%, P < 0.01], however, the SM-FOK levels of the MCI patients with different
      judgment and recognition were all not significantly different from those of the
      HC group (all P > 0.05). CONCLUSION: The MCI patients overestimate their memory
      performance on episodic FOK, but their SM monitoring is not impaired. The deficit
      of memory monitoring in MCI may be the foundation of subjective memory complaints
      and is useful for diagnosis of MCI. EM and SM monitoring may depend on different
      neural mechanisms.

PMID- 19595254
TI  - [Assessment of flexibility in adolescent idiopathic scoliosis by curved planar
      reformation using multi-slice spiral CT scanning].
AB  - OBJECTIVE: To investigate the role of curved planar reformation (CPR) using multi
      slice spiral CT scanning to evaluate the coronal and sagittal plane in scoliosis
      so as to affirm the features of supine coronal and sagittal plane in idiopathic
      scoliosis. METHODS: Thoracic and lumbar spine multi-slice spiral CT scanning was
      undertaken on 45 patients with adolescent idiopathic scoliosis (AIS), all female,
      age 10 - 18. CPR was used to reconstruct the spine coronal and sagittal planes
      respectively. The values of main curve and compensate curve Cobb angles were
      obtained and compared with those obtained by X-ray films. RESULTS: The average
      CPR coronal main curve Cobb angle was smaller by 10.17 degrees than that obtained
      by standing position film. The average CPR coronal compensate curve Cobb angle
      was smaller by 6.97 degrees than that obtained by standing position film. For
      scoliosis coronal flexibility assessment, fulcrum-bending method offered better
      surgical correction result than other methods. Only the post-operational Cobb
      angle was different between the 10 - 14 year-old group and 15 - 18 year-old
      group. Bending film showed differences in correction rate and flexibility rate
      between the main thoracic group and main lumbar/thoracolumbar group. The
      correction rate and flexibility rate of main curve and compensate curve of the 10
      - 14 year-old group were significantly higher than those of the 15 - 18 year-old
      group. In the sagittal plane, the CPR thoracic kyphotic angle (T5-T12) and upper
      thoracic curve kyphosis of the main thoracic group were both smaller than those
      of the main lumbar/thoracolumbar group. The CPR thoracic kyphotic angle (T5-T12)
      of the 10 - 14 year-old group was significantly smaller than that of the 15 - 18
      year-old group. Correlation analysis showed that the CPR main curve flexibility
      and bending film flexibility were positively corrected with the surgical
      correction rate. CONCLUSION: CPR using multi-slice spiral CT scanning is able to
      obtain multiple three-dimensional assessment by one scanning and is helpful in
      scoliosis curve type diagnosis and scoliosis 3D analysis.

PMID- 19595255
TI  - [Intraobserver and interobserver reliability of the King, Lenke, and PUMC
      classification systems for idiopathic scoliosis].
AB  - OBJECTIVE: To evaluate the intraobserver and interobserver reliability and main
      influencing factors of the King, Lenke, and PUMC classification systems for
      idiopathic scoliosis (IS) using radiographs that had not been premeasured.
      METHODS: Fifty-six patients with IS, 9 male and 47 female, aged 15.4 (11 - 18),
      underwent preoperative X-ray photography of spine standing full-length
      posteroanterior and lateral films and left and right supine side-bending
      radiographs. The films were read by four orthopedic surgeons independently to do
      measurement and typing according to the King, Lenke, and PUMC classification
      systems respectively. Two weeks later, the sequence of the X-ray films was re
      ordered and the 4 surgeons read them and did measurement and typing once more.
      The average percentage of intraobserver and interobserver agreement was
      calculated. Kappa coefficients were used to determine the intraobserver and
      interobserver reliability. RESULTS: King classification demonstrated fair
      interobserver reliability and excellent intraobserver reliability. The mean
      interobserver reliability was 65.8% (Kappa coefficient = 0.542), while the
      intraobserver reliability was 82.6% (Kappa coefficient = 0.767). The main reason
      of disagreement was distinguishment of the King type II and type III. Another
      reason was assessment of King type V. The complete Lenke classification
      demonstrated poor reliability. The mean interobserver reliability was 50.0%
      (Kappa coefficient = 0.438), and the intraobserver reliability was 47.0% (Kappa
      coefficient = 0.402). The 3 components of Lenke classification had fair
      interobserver and intraobserver reliability when they were examined separately.
      The main reasons for disagreement arose from judging whether there was a
      structural upper thoracic curve and assigning sagittal thoracic modifier. The
      PUMC type demonstrated excellent intraobserver and interobserver reliability with
      a mean interobserver reliability of 87.8% (Kappa coefficient = 0.757), and a mean
      intraobserver reliability of 92.9% (Kappa coefficient = 0.958). Its subtypes
      demonstrated fair agreement with the mean interobserver reliability of 70.2%
      (Kappa coefficient = 0.629), and a mean intraobserver reliability of 74.1% (Kappa
      coefficient = 0.674). The main reasons for disagreement were definition of a
      curvature and Cobb angle measurement. CONCLUSION: King and PUMC classification
      systems have higher interobserver and intraobserver reliability than Lenke
      classification. The reliability levels of the 3 classification systems are all
      influenced by many factors. Judgment of an upper thoracic curve, variable of Cobb
      angle measurement, and relationship of the central vertical sagittal line to apex
      of curve are the common reasons for disagreement in these 3 classifications.

PMID- 19595256
TI  - [Fetal anomalies in second trimester in recent ten years: clinical analysis of
      116 cases].
AB  - OBJECTIVE: To evaluate the prevalence of fetal anomalies in recent 10 years and
      explore the effective methods of early diagnosis and treatment. METHODS: The
      clinical and pathological data of 116 pregnant women who underwent induced
      abortion in the second trimester due to fetal anomalies 1998 - 2007 were analyzed
      retrospectively. RESULTS: The fetal anomaly rate in the period 2003 - 2997 was
      8.7 per thousand, significantly higher than that in the period 1998 - 2002 (3.1
      per thousand, P < 0.001). The diagnostic methods of fetal anomalies used during
      the period 2003 - 2007 did not show significant differences compared with those
      used during the period 1998 - 2002. The gestational week when the fetal anomalies
      were detected in 2002 - 2007 was 19.3 weeks, not significantly preceded compared
      with that during 1998 - 2002 (22.4 weeks, P > 0.05). The top 5 fetal anomalies
      with high incidence rates were Down' syndrome, anencephalus, lip/palate cleft,
      fatal cystic hygroma of the neck, and cardiac anomalies. There were 30 cases of
      advanced maternal age over 35 years, 60.0% of whose fetuses showed chromosome
      abnormality. CONCLUSION: The incidence of fetal anomalies increases in recent
      years. The risk of fetal anomalies is high in the pregnant women in elder age.
      Pregnancy in advanced maternal age show high risk to occur fetal anomaly. Better
      approaches to diagnose fetal anomaly earlier are still to be found.

PMID- 19595257
TI  - [rh-endostatin in combination with docetaxel and carboplatin as adjuvant
      treatment for non-small lung cancer].
AB  - OBJECTIVE: To evaluate the efficacy of Endosteal(TM) (rh-endostatin, YH-16)
      combined with docetaxel and carboplatin (TP) regimen for the adjuvant treatment
      of non-small lung cancer (NSCLC) and its impact on circulating blood markers.
      METHODS: 36 patients with stage Ib-IIIa postoperative NSCLC, were randomly
      divided into the treatment group, Endosteal(TM) plus TP regimen, and the control
      group, TP regimen only, respectively. DFS and toxicities of patients were
      observed. The numbers of CEC and the levels of tumor marker CEA, NSE and CYFR21-1
      were measured. RESULTS: The numbers of CEC and the levels of CEA, NSE and CYFR21
      1 decreased after treatment. There were significant differences in CEC and NSE
      between treatment group and control group after four cycles of treatment,
      respectively (P = 0.016 and 0.013). Disease-free survival time (DFS) was longer
      in treatment group than control group but without significant difference. CEC was
      significantly increased in recurrent and metastasis cases and decreased after
      effective treatment. CONCLUSION: Endosteal(TM) combined with TP regimen seem to
      be superior to TP alone in some short term index for the treatment of
      postoperative NSCLC even though long-term survival is still anticipated. CEC, as
      a biomarker, may be useful in predicting the efficacy of the such synergistic
      treatment.

PMID- 19595258
TI  - [Diagnosis of solid-pseudopapillary tumor of the pancreas and the value of post
      processing in the surgery by spiral CT].
AB  - OBJECTIVE: To study the CT manifestations of the solid-pseudopapillary tumor of
      the pancreas (SPTP) and to explore the value of post-processing in the surgery.
      METHODS: Clinical and CT features of 14 patients with SPTP proved pathologically
      were retrospectively analyzed. RESULTS: (1) 13 tumors were composed of different
      proportions of solid and cystic parts and 1 tumor was composed of solid part
      only. The solid portions demonstrated slight enhancement in the arterial phase
      and marked enhancement in the portal venous phase on post-contrast CT. The cystic
      portions appeared hypo-attenuation on both pre- and post-contrast CT images.
      Tumors were encapsulated and the capsule enhanced markedly with well-defined
      margins on post-contrast images. (2) Dilatation of the common bile duct or
      pancreatic duct wasn't seen in all of the cases and 1 case with the right adrenal
      ganglioneuroma. (3) 5 tumors located in the head of the pancreas, 3 of which with
      the superior mesenteric vein compression and displacement, in 2 cases the vessels
      were partially encapsulated by tumor. 6 tumors located in the tail of the
      pancreas, 3 of them with splenic hilum compression and multiple splenic vein
      tortuosity and dilatation, the veins drained into superior mesenteric vein
      anteriorly and posteriorly of the tumor. Splenic vein compression and posterior
      displacement occurred in 2 cases. In one case, there was no clear margin between
      the tumor and the splenic hilum. CONCLUSION: The SPTP has characteristic CT
      findings and correct diagnosis could be made by combining clinical features. The
      relationship of the lesions and surrounding structures could be revealed by the
      post-processing and was helpful for the operation.

PMID- 19595259
TI  - [Clinical and pathological features of glycogen storage disease type III].
AB  - OBJECTIVES: To summarize the clinical and pathological features of glycogen
      storage disease (GSD) type III. METHODS: The clinical data of 12 GSD type III, 8
      males and 4 females, aged 2 - 27, were collected. The biopsy specimens of
      quadriceps muscle of thigh underwent HE and histochemical staining and light and
      electron microscopy. RESULTS: The main clinical feature were hepatomegaly and
      hypoglycemic symptoms, slow growth, and microsome since childhood, while myopathy
      was mild. Laboratory findings included low plasma glucose (n = 12), high liver
      transaminases (n = 12), increased CK (n = 11), mild metabolic acidosis (n = 11),
      hyperlipemia (n = 9), elevation of blood lactate (n = 5), high uric acid (n = 1),
      and decrease of serum carnitine level (n = 1). One patient had echographic
      evidence of cardiomyopathy. 11 patients were postprandial adrenalin stimulation
      test positive. Raw corn starch therapy was used on all patients and showed
      effective on liver manifestations. Muscle biopsy showed vacuolar myopathy, PAS
      positive glycogen granules in muscle fibers, small foci of intense ACP
      reactivity, and deposit of lipid droplets. CONCLUSION: GSD type III exhibits a
      clinical heterogeneity. Besides hepatic symptoms, myopathy and cardiomyopathy
      should be addressed adequately. The degree of pathological change of muscles is
      not significantly related to the degree of functional impairment, duration of
      disease, and level of CK.

PMID- 19595260
TI  - [The empirical study in transplantation of bone marrow mesenchymal stem cells for
      acute myocardial infarction].
AB  - OBJECTIVE: To study the effect of (60)Co gamma ray on proliferation and
      differentiation potency of MSC. To evaluate the function of heart after early
      stage of acute myocardial infarction (AMI) in rats by transplantation of MSC.
      METHODS: Irradiated MSC was cultured with the method of adherent culture, the
      ability of its proliferation was detected by Methyl thiazolyl tetrazolium (MTT)
      shade selection test. The express of Cardiac troponin T (C-TNT) and beta-myosin
      heavy chain (beta-MHC) in MSC were detected by Reverse transcriptase-polymerase
      chain reaction (RT-PCR), which was induced by 5-azacytidine. Using a rat model of
      AMI, irradiated and unirradiated MSC were transplanted into myocardium after
      infarction. At 4 weeks, the cardiac dimension and functions were assessed by
      echocardiography and hemodynamics, the microvessel density were detected after
      VIII factor immunohistochemistry stain. RESULTS: The ability of proliferation in
      4Gy group was depressed. C-TNT and beta-MHC expressed somewhat in unirradiated
      group. When compared with the control group (6.6 +/- 0.6), the microvessel
      density in both transplanted groups (12.7 +/- 2.2, 11.5 +/- 2.1) increased,
      contributing to improvement in cardiac function and dimension. CONCLUSION: MSC
      with or without differentiation potency can improve cardiac function equally at
      the early stage of AMI.

PMID- 19595261
TI  - [Influence of chronic cerebral hypoperfusion on gap junction ultrastructure and
      expression of connexin (Cx) 36, Cx32, and Cx26 in hippocampus: experiment with
      rats].
AB  - OBJECTIVE: To investigate the Influence of chronic cerebral hypoperfusion on gap
      junction ultrastructure and expression of connexin (Cx)36, Cx32, and Cx26 in
      hippocampus the microstructure of gap junction and the expression of gap junction
      subunits in the hippocampus of cognition impaired animals. Cognition impairment
      was induced by the permanent occlusion of the carotid arteries (2-VO). METHODS:
      Twenty-seven Wistar rats underwent two-vessel occlusion (2-VO, ligation of
      bilateral common carotid arteries) and then were randomly divided into 2 equal
      groups: 2-VO 3 week, 2-VO 8 week and 2-VO 12 week groups to undergo Morris water
      maze test 3, 8, and 12 weeks later to observe the spatial learning and memory
      ability. Another 9 rats underwent sham operation to be used as control group.
      After Morris water maze test the rats were killed. The brains were taken out from
      3 rats from each group to undergo thin-section transmission electron microscopy
      to observe the ultrastructure of the gap junctions in the CA1 area of
      hippocampus. RT-PCR and Western blotting were used to detect the mRNA and protein
      expression of Cx 36, Cx32, and Cx26 in the hippocampus of the other 27 rats, 6
      from each group. RESULTS: Compared to the control group, the density of
      cytomembrane of gap junction was lower, the interspace of gap junction were
      larger in the 2-VO 3 week group, and these abnormalities were gradually improved
      in the 2-VO 8 and 12 week groups. The mRNA and protein levels of Cx36 and Cx32 of
      the three 2-VO groups were the lowest in the 2-VO 3 week group, and then
      gradually increased, however, all significantly lower than those of the control
      group (all P < 0.05). The mRNA level of Cx26 was not altered significantly, while
      the protein expression levels of Cx26 in the three 2-VO groups were all higher
      compared with the control group (all P < 0.05). CONCLUSION: The altered neuronal
      gap junction may participate in the cognition impairment caused by chronic
      cerebral hypoperfusion.

PMID- 19595264
TI  - Cutaneous morphometric parameters of young FVB/N mice sustained in aged mice and
      in calorically restricted transgenic alphaMUPA mice.
AB  - Caloric restriction (CR) extends the lifespan of diverse animal species and is
      currently the only therapeutic intervention known to attenuate aging and increase
      longevity in laboratory animals. The effect of CR on intrinsic skin aging is not
      well understood. To study this issue, we took advantage of transgenic alphaMUPA
      mice that spontaneously eat less (20-30%) when fed ad libitum and live longer
      compared to their wild type (WT) FVB/N control mice. Herein we determined
      morphometric skin parameters in young (6-7 months) and aged (17-18 months)
      alphaMUPA and WT mice. In addition, we transplanted skin grafts excised from the
      aged or young alphaMUPA and WT mice into both types of young mice, to test
      whether the systemic environments of alphaMUPA and WT mice could affect the
      grafts differently. The results have shown that the mean epidermal thickness,
      number of hair follicles and number of dermal blood vessels were similar in all
      four groups regardless of age or mouse type. In addition, the post-graft
      specimens of all four groups exhibited increase in all parameters measured, in
      particular a remarkable 6-7 fold increase in epidermal thickness. However, no
      significant differences were detected in the post-graft samples between the four
      experimental groups. Our findings indicate that, at least in FVB/N mice,
      parameters measured in normal or grafted skin depend primarily on the intrinsic
      cutaneous capacity rather than on circulating factors as determined by age or
      reduced calories.

PMID- 19595265
TI  - Expression of MAGE-A1, MAGE-A3/4 and NY-ESO-1 cancer-testis antigens in fetal
      testis.
AB  - Immunohistochemical expression of MAGE-A1, MAGE-A3/4 and NY-ESO-1/LAGE-1 cancer
      testis antigens (CTA) was assessed in 24 fetal testes from 15th to 36th week of
      gestation. Three monoclonal antibodies were used for immunohistochemical
      staining: 77B recognizing MAGE-A1, 57B recognizing multiple MAGE-A CTA, and D8.38
      recognizing NY-ESO-1/LAGE-1. Expression of MAGE-A1 was not observed in fetal
      testis samples, whereas multi-MAGE-A and NY-ESO-1/LAGE-1 specific reagents
      stained pro-spermatogonia in all samples with different expression levels during
      the period of fetal development observed. Significant expression of MAGE-A3/4 and
      almost continuous expression of NY-ESO-1 in fetal testes after 22nd week of
      gestation suggested their important role in the development of sex cords and pro
      spermatogonia in particular.

PMID- 19595266
TI  - The incidence of basal cell carcinoma in Croatia: an epidemiological study.
AB  - The aim of the study was to investigate the basal cell carcinoma (BCC) incidence
      in Croatia in the 2003-2005 period. Data were collected from University
      Department of Dermatology and Venereology, Zagreb University Hospital Center and
      National Cancer Registry. The age-specific incidence rate and age-standardized
      incidence rate were calculated per 100,000 inhabitants according to the latest
      population census in Croatia from 2001. In the study period, there were 7,244 BCC
      cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the
      Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age
      standardized incidence rate (adjusted for the world standard population) was 33.6
      for men and 24.5 for women. The head and neck were almost exclusive localizations
      of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of
      BCC was high in both littoral and inland counties of Croatia. Study results will
      serve as reference figures on studying the trend of BCC incidence in Croatia and
      Europe in the forthcoming years.

PMID- 19595267
TI  - Why dermatology patients are hospitalized? A study from Pakistan.
AB  - In most countries, there are no specified protocols or guidelines for admitting
      dermatology patients and admission criteria depend on assessment and sometimes
      the whim of the dermatologist. Although the severity and extent of the disease
      are the commonest reasons for hospitalizing dermatology patients, sometimes other
      factors also operate to provide comfort to the patient. This study was carried
      out to determine the reasons for hospitalizing patients on dermatology beds in
      secondary care hospitals of Pakistan. A questionnaire comprising patients'
      demographic data, diagnosis, specific reasons for hospitalization and length of
      hospital stay was sent to dermatologists of 10 secondary care hospitals in the
      country. The data received in response were processed and analyzed using the SPSS
      10 computer program. A total of 310 patients were included in the study. Patient
      age ranged from 1 to 87, mean 28.87+/-12.32 years. The severity and extent of the
      disease (n=122; 39.3%), outpatient treatment failure (n=57; 18.4%) and need for
      further observation and/or investigations (n=51; 16.5%) were the most common
      reasons for hospitalizing these patients. Hospital stay of the patients ranged
      from 2 to 30, mean 9.82+/- 6.43 days. Scabies (n=56; 18.1%), chickenpox (n=52;
      16.8%) and eczema (n=41; 13.2%) were the most common diagnoses.

PMID- 19595268
TI  - Neurofibromatosis type 1 associated with dysplastic nevus syndrome.
AB  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder that primarily
      affects the development and growth of neural cell tissues. It causes tumors to
      grow on nerves and produces other abnormalities such as skin changes and bone
      deformities. Dysplastic nevus syndrome (DNS) represents multiple atypical nevi
      associated with polygenetic inheritance pattern and may rarely occur together
      with NF-1. DNS type A is a marker of increased melanoma risk, while melanoma has
      been rarely reported in patients with NF-1. We describe a case of NF-1 type A
      with DNS presenting with multiple neural tumors, cafe-au-lait spots, hamartomas
      in globus pallidus and pigmented melanocytic iris hamartomas (Lisch nodules). The
      importance of close follow up of nevi in such patients with NF-1 and DNS for the
      development of melanoma as well as other NF-1 associated skin disorders and with
      multidisciplinary approach to other associated diseases is highlighted.

PMID- 19595269
TI  - Minocycline-induced skin pigmentation: an update.
AB  - Minocycline is a commonly used antibiotic for long-term treatment of acne
      vulgaris. A well-documented and cosmetically dis-pleasing side effect is skin
      pigmentation. Three distinct types occur: Type I, blue-black/grey pigment on the
      face in areas of scarring or inflammation associated with acne; type II, blue
      grey pigment on normal skin on the shins and forearms; type III, diffuse muddy
      brown discoloration in areas of sun exposure. Types I and II stain for iron and
      melanin extracellularly and within macrophages in the dermis. Type III shows
      nonspecific increased melanin in basal keratinocytes and dermal melanophages
      staining for melanin only. The etiology of this pigmentation is unknown, but may
      be related to polymerized reactive metabolites, insoluble chelation products, and
      lengthy treatment durations of minocycline compared to other tetracyclines. Types
      I and II tend to resolve slowly over time, whereas type III persists
      indefinitely. Treatment involves early recognition, discontinuation of the drug,
      sun protection, and laser for persistent pigmentation.

PMID- 19595270
TI  - Unrecognized dermatophyte infection in ichthyosis vulgaris.
AB  - A case of unrecognized widespread dermatophyte infection associated with
      ichthyosis vulgaris and atopy is described. Our patient was a young woman in
      which the diagnosis of ichthyosis vulgaris and atopic dermatitis blocked the
      recognition of widespread dermatophyte infection for more than six months. The
      case showed some clinical peculiarities in terms of both extent of lesions and
      their clinical appearance.

PMID- 19595272
TI  - Hypertrophic lupus erythematosus: case report.
AB  - Discoid lupus erythematosus is the most common form of cutaneous lupus
      erythematosus. It is more common in women than in men, in individuals between 20
      and 40 years of age. It is an inflammatory autoimmune disease in which
      genetically predisposed individuals are stimulated by hormonal and a variety of
      exogenous factors including UV radiation, stress, infections, and even
      temperature changes. Lesions are characterized by erythema, hyperkeratosis and
      atrophy. Typical sites are light-exposed areas, i.e. forehead, nose, cheeks,
      upper part of the back, upper chest, and dorsal aspects of the hands and feet. A
      case of lupus erythematosus hypertrophicus with very good and rapid treatment
      results with antimalarials and topical corticosteroid is presented.

PMID- 19595271
TI  - Malignant melanoma of glans penis and prepuce treated with organ-preserving
      surgical procedure.
AB  - The authors present a case of malignant melanoma of glans penis and prepuce. An
      organ-preserving operative procedure using buccal mucosa was performed with
      subsequent inguino-femoral modified lymphadenectomy. There was no disease
      progression during the follow-up period of twelve months.

PMID- 19595273
TI  - Halo phenomenon with regression of acquired melanocytic nevi: a case report.
AB  - We report a case of halo-phenomenon in excisional biopsy of junctional nevi in a
      19-year-old girl. The diagnosis was established histopathologically because of
      the lack of clinical halo and unspecific dermoscopic features. Clinicopathologic
      difficulties in establishing the diagnosis of these pigmented lesions,
      etiopathogenesis and differential diagnosis of halo nevi are emphasized.
      Dermatologists should be familiar with the possible changes in benign melanocytic
      nevi, halo reactions and possible complete regression of melanocytic nevi.
      Diagnostic difficulties are seen in the ultimate phase of regression when
      melanocytes are diminished or destroyed with immune reaction.

PMID- 19595274
TI  - Clear cell hidradenoma of the gluteal region: a case report.
AB  - Clear cell hidradenoma is a rare skin appendage tumor. A 41-year-old female
      presented with right gluteal mass. Excisional biopsy of the mass was performed.
      Under the epidermis, an eosinophilic-cytoplasm, uniform-appearance, oval-round
      nucleus, benign tumor with cystic and solid components was detected. These
      results were consistent with clear cell hidradenoma. The patient had not been
      given postoperative adjuvant treatment and has been under follow up free from
      disease for 2 years.

PMID- 19595275
TI  - News from the first regional symposium on hereditary epidermolysis bullosa
      (Mediterranean - Central and Eastern Europe).

PMID- 19595277
TI  - [Long-term experience with the combined ARBOND hydroxyapatite coating in implant
      osteointegration].
AB  - PURPOSE OF THE STUDY: The hydroxyapatite coating of an implant surface provides
      osteoactive conditions that can support osteointegration of cementless joint
      arthroplasties. However, the possibilities of hydroxyapatite degradation,
      resorption and delamination that may become responsible for failure of total hip
      arthroplasty (THA) have been reported. The aim of the study was to assess the
      properties of Arbond hydroxyapatite coating by comparing the long-term survival
      of implants identical in construction but different in surface coating. MATERIAL:
      One group (HA) comprised 86 patients (100 THAs) with an average age of 45.14
      years (range, 22.3 to 77.4 years) at the time of surgery who received a femoral
      stem (Walter) with a coating of Arbond sprayed over the proximal half. The other
      group (control) included 92 patients (100 THAs) with an average age of 49.7 years
      (range, 33 to 68.7) who had an identical femoral component without coating. In
      both groups the conical-shaped acetabular cup (Walter) and femoral head made of
      sintered ceramics were used. The patients in whom one or both components were
      replaced or extracted were not included in the final clinical evaluation (Harris
      Hip Score). For the statistical analysis of survival, a stable component still in
      place at the date of the revision procedure was regarded as surviving; a lose
      component at the same date was considered a failure. Finally, 71 hips of the HA
      group followed up for an average of 15.51 (range, 5.6 to 18.56) years and 39
      control hips at an average follow-up of 14.19 (range, 6.24 to 18.48) years were
      clinically evaluated. The data of patients who died in the course of study (HA
      group, 11; control group, 14) were included in the clinical evaluation with the
      date of their last follow-up. METHODS: For both groups, the Kaplan-Meier survival
      curves were constructed for overall survival and for the survival of acetabular
      and femoral components separately. Differences in survival curves were evaluated
      with the use of Gehan's Wilcoxon test. Component survival was also calculated
      using 15-year life-table survivorship analysis. Differences in variables under
      study were assessed with the use of the two-tailed Student's t-test. A p value of
      less than 0.05 was considered significant. RESULTS: A total of 29% hips were
      revised in the HA group, 27% for aseptic loosening of the acetabular cup, in 2%
      both components were removed because of deep infection. In the control group
      revision procedures were performed in 61% of the hips. Except for one case of
      deep infection (1%), the reason was cup loosening in 30%, stem loosening in 12%
      and both components loosening in 18% of the hips. The HA group showed a
      significantly longer survival of both total hip prostheses and individual
      components. The final HHS was significantly better than the initial score in both
      groups. There was no difference in the degree of improvement between the two
      groups. The radiographic data showed full osteointegration of stems in the HA
      group. The control group, on the other hand, had 87% of the stems with
      translucent lines in zone I and zone VII according to Gruen's classification.
      DISCUSSION: The significantly longer survival of hips in the HA group gives
      support to the use of hydroxyapatite coating in total hip arthroplasty. The
      poorer results in grit-blasted implants, as compared with the literature data,
      can be explained by allow degree of roughness of the Walter implant surfaces.
      CONCLUSIONS: The combined Arbond hydroxyapatite coating improves conditions for
      implant osteointegration in the bone.

PMID- 19595278
TI  - [Periprosthetic fractures of the hip].
AB  - PURPOSE OF THE STUDY: It is the aim of our study to present the results of our
      way of treatment of the periprosthetic fractures, with the cemented as well as
      the cement-free stems. MATERIAL: From 1.1.1988 until 31.3.2005 we operated 42
      periprosthetic fractures of the hip in 41 patients. 31 of our patients were
      females, 10 of them males. In 22 cases we operated the right side, 18 times the
      left side and once we had to operate both sides, but at different times. We used
      the Vancouver classification scale for the grading of the fractures. In our study
      we excluded type A fractures; we registered 41 type B fractures and one only type
      C fracture. The reason for periprosthetic fracture in all these 42 cases was
      definitely a trauma. In 6 cases we found pre-existing loosening of the stem. We
      have grouped our patients under two headings: 1. Primary cemented stems (n=13) 2.
      Primary cement-free stems (n=29) The average age at the time of primary operation
      was 63.6 years in the group of cemented stems and 67.2 years with the cement-free
      implants. METHODS: The principle of this operation lies in a stable technique of
      osteosynthesis. If one operates on a stable stem one uses a one and only
      technique of osteosynthesis. Patients who also suffer from a loosening of the
      stem, are treated by replacement of the stem combined with a particular form of
      osteosynthesis. We generally use a transgluteal access with an L-shaped
      detachment of the Musc. vastus lateralis. In the group of cemented stems (n=13)
      we carried out a replacement of the stem 6 times and in the group of cement-free
      stems (n=29) we had to replace the implant on 7 occasions. Analysing the
      osteosynthesis technique we find the use of titanium cerclages and titanium
      elements on 35 occasions, in both groups taken together. As implant for the stem
      we preferred the modulated revision stem according to Zweymuller. Clinical post
      operational examination of our patients was carried out according to the Merle
      d'Aubigne score and two x-rays at different levels. RESULTS: After an average
      post-operational check-up time of 3 years and 2 months, we were able to examine 8
      patients with cemented stems (61.5%), 4 of whom had replacement of the stem by a
      cement-free implant. In the cement-free group we evaluated 24 patients after an
      average time of 4 years and 11 months. In this group we had 5x a replacement of
      the stem, 3x of these we could operate cement-free. The post-operational
      radiological check showed an excellent building-up of bone structure without any
      dislocation of the implant in all 32 cases. DISCUSSION: The average age of our
      patients shows 77 years with those with cemented stems and 74.5 years in the ones
      with cementfree implants. Analysis of the cemented stems shows a loosening rate
      of more than 50%, which coincides with the findings of many other authors. After
      a couple of years using cups of polyethylene we were confronted with the problem
      of the so-called Polyethylene disease. These alterations may finally lead to a
      loss of bone quality, to mechanical loosening of the implant and an increase in
      danger of fracture. When we discuss the group of patients with cement-free stems
      and compare them to those with cemented ones, we find a number of quite different
      characteristics. B2 fractures appear in a quite higher number of patients with
      cemented and loosened stems. In this regard, our own study is congruent with the
      studies of other authors. In the cement-free group we had 75% B1 fractures with a
      stable stem. The explanation for these figures is, that the cement-free implants
      were well incorporated in the bone structure. CONCLUSIONS: The choice of
      operative procedure when treating periprosthetic hip fractures depends on the
      type of fracture and the stability of the prosthesis. Our own very positive
      experiences and the then emerging results lead to a certain strategy in
      procedure. That means, for us, the use of a cement-free modulated revision stem
      according to Zweymuller combined with a particular technique of osteosynthesis,
      using titanium cerclages and titanium elements.

PMID- 19595279
TI  - [Complications associated with the surgical treatment of acetabular fractures].
AB  - PURPOSE OF THE STUDY: To analyse retrospectively complications of the surgical
      treatment of displaced acetabular fractures. MATERIAL: In the years 1996 to 2006
      a total of 251 patients with acetabular fractures were treated. The group
      comprised 162 men and 89 women; the average age was 35 years. The average follow
      up was 71 months (range, 16 to 138). Based on the AO classification, type A
      fractures were found in 58%, type B in 23% and type C in 19% of the patients.
      Indications for surgical intervention were hip instability or hip incongruence.
      RESULTS: The complications included intra-operative, and early and late post
      operative problems. Of the intra-operative complications, 2% were vascular
      injuries, 5% were damage to the static nerve, 13% were due to incomplete
      reduction and 2% due to bone non-union. Early post-operative complications in
      five patients (2%) required revision surgery for early infection in two,
      haematoma in the wound in one and failed osteosynthesis in two patients. In one
      patient failed osteosynthesis was associated with hip dislocation. Late
      complications included aseptic necrosis in 7%, post-traumatic arthritis in 17%,
      para-articular ossification grades III and IV of the Brooker classification in 7%
      and late infection in 0.5% of the patients. DISCUSSION: The outcome of surgical
      treatment depends on quality reconstruction of the articular surface and
      complications, and is related to the fracture type and method of treatment. Not
      every poor outcome means it is a complication, nor is it always related to the
      type of fracture. Some fracture types are bound to heal poorly. The complex
      anatomy of the joint involves rather frequent injury to nerve structures and
      imperfect reduction and fixation. CONCLUSIONS: The most frequent complication is
      the development of post-traumatic arthritis due to imperfect reduction. However,
      the current limit of achieving correct reduction and weight-bearing surface
      reconstruction remains an open issue. Aseptic necrosis in type A fractures was
      three-times as high as in type B and C fractures. Imperfect reconstruction of the
      acetabulum and failure to restore hip joint congruence were twice higher in type
      B than type A and C fractures.

PMID- 19595280
TI  - [The Ponseti method of treatment of congenital clubfoot--first experiences].
AB  - PURPOSE OF THE STUDY: To provide a detailed description of the Ponseti method and
      report the first results of its use, including factors that played a role.
      MATERIAL AND METHODS: In the 2005-2007 period, 91 patients with idiopathic rigid
      clubfoot (133 feet) were treated by the Ponseti method. The group comprised 62
      boys and 29 girls. In most patients the Ponseti method was used as primary
      treatment, or by 3 months of age when previous treatment failed. In five children
      this treatment was started between the 3rd and 8th months of age. The result were
      evaluated by the criteria described by Richards et al., who distinguished four
      groups. The result was regarded as good when a permanent plantigrade foot was
      achieved (group 1). Plantigrade feet likely to require posterior release later
      were considered indeterminate rusults (group 2). Feet that needed posterior
      release, anterior tibial muscle transfer or lateral column shortening fell in the
      fair result group (3). Feet requiring complete subtalar release were classified
      as poor results (group 4). The results achieved in each year were statistically
      evaluated using Fisher's test (p<0.05). RESULTS: The overall evaluation for 3
      years showed good results in 70%, indeterminate in 7.5%, fair in 6.76% and poor
      in 15.8% of the treated feet. A detailed analysis for each year revealed that, in
      2005, good results (50%) were recorded in a significantly lower number of feet
      than in 2006 (72.2%; p=0.032) and 2007 (93%; p<0.001). On comparison of the years
      2006 and 2007, good results in 2007 were found in a significantly higher number
      of feet than in 2006 (p=0.019). The poor results were due to 1) very rigid feet
      (6%); 2) initial problems with availability of Denis-Brown splints (19 feet;
      14.5%); 3) problems with shoes not made to custom and not fitting patient's
      little feet (20 feet; 15%) 4) faulty techniques of correcting the deformity (4
      feet); 5) poor family cooperation in compliance with the bracing protocol (15
      feet; 11.2%). Some of the factors were combined. A delayed beginning of the
      treatment had no significant effect on the results. DISCUSSION: Our 3-year
      results of clubfoot treatment, by which plantigrade foot position was acheved on
      average in 77.5% of the patients, are in agreement with those achieved outside
      Ponseti centres. However, there were clear differences, with the worst results in
      2005. The results comparable with those of Ponseti and his co-workers were
      achieved by us only in 2007. In accordance with the findings of Richards et al.
      we suggest that the percentage of short-term good results can change
      insignificantly within 4 years because of increased recurrence of deformities.
      CONCLUSIONS: Although our initial results were worse than reported in the
      literature, it can be concluded that the Ponseti method of treating idiopathic
      clubfoot is more efficient that the methods used previously and can be
      recommended as an efficient, safe and economical technique. Good compliance with
      the protocol improves the therapeutic results.

PMID- 19595281
TI  - [Treatment of trochanteric fractures by percutaneous compression plate].
AB  - PURPOSE OF THE STUDY: To present a new type of percutaneous compression plate
      (PCP) for a minimally invasive method of treating trochanteric hip fractures.
      MATERIAL: Between September 2004 and December 2006, a total of 66 patients with
      hip fractures were treated by minimally invasive percutaneous osteosynthesis
      involving a PCP. The average age of the patients was 74.5 years (range, 27-95
      years). The fractures were classified as pertrochanteric (AO31, A1.1-A2.3) in
      73%, femoral neck fracture (AO31, B2) in 20%, and intertrochanteric fracture
      (AO31, A3.1) in 7% of the patients. METHODS: Reduction was performed under
      conduction or general anaesthesia on a traction table, using an X-ray image
      intensifier system. Reduction and intra-operative temporary stabilisation of the
      fracture was facilitated by a posterior reduction device. Access was gained and a
      PCP was inserted through two incisions at the lateral side of the proximal femur.
      RESULTS: The patients were followed up for at least 6 months. Radiographic union
      was found on average at 3 months post-operatively. No pseudoarthrosis or implant
      failure was recorded. At 6-month follow-up, 81% of the patients were able to walk
      without walking aid or with one walking cane only. Two crutches were used by 8%
      of the patients.To walk without help was impossible for 11% of the patients whose
      mobility had already been limited before the injury. DISCUSSION: PCP
      osteosynthesis for trochanteric fractures is a novel minimally invasive approach
      providing a better treatment of the fracture. Compared to dynamic hip screw
      osteosynthesis used before, PCP allows for earlier weight bearing and noticeably
      reduces blood loss. Implant construction as well as post-operative controlled
      impaction of the fracture minimize the risk of osteosynthesis failure. The simple
      instrumentation construction enables us to reduce operative time. CONCLUSIONS:
      The percutaneous compression plate is a contribution to minimally invasive
      osteosynthesis of trochanteric fractures. An increase in rotational stability of
      the implant due to its biaxial telescopic construction allows for earlier weight
      bearing of the extremity, thus facilitating the patient's earlier return to
      everyday life activities. It also reduces operative trauma, blood loss and post
      operative complications.

PMID- 19595282
TI  - [Chronic lunotriquetral instability of the wrist. Presentation of our method of
      treatment].
AB  - PURPOSE OF THE STUDY: One of the causes of pain on the ulnar side of the wrist is
      post-traumatic lunotriquetral (LTq) instability, which is difficult to detect on
      radiographs. For diagnosis, arthroscopic examination is most reliable. The
      methods for treatment of LTq instability include mere immobilization, ligament
      reconstructions and LTq joint stabilization with Kirschner's wires in acute
      conditions, and stabilization of the LTq joint by tenodesis or arthrodesis. In
      this study our method of treating chronic isolated injury to the lunotriquetral
      ligament is described. MATERIAL: The group comprised 43 wrists with isolated
      lunotriquetral ligament injuries diagnosed by arthroscopy. In 19 patients with
      persisting complaints, stabilization was performed using our original method. At
      4 months after surgery, the results were evaluated by the method of Green and
      O'Brien. METHODS: Access to the LTq joint was gained through the fifth extensor
      compartment. At about 3 cm proximal to the ulnar head, one third of the extensor
      capri ulnaris (ECU) tendon was detached, without doing damage to the tendinous
      sheath on the ulnar head, and stretched distally up to the triquetrum-hamate
      joint level. Using a 3.2-mm drill, a tunnel was made on the dorsal side of the
      triquetrum, starting at the distal third of the ulnar side of the triquetrum and
      opening at the attachment site of the dorsal LTq ligament. In the middle part of
      the dorsal side of the lunate, a groove 4 mm deep and 6 mm long was made with a
      cutter and a two-suture Mitek anchor was inserted in its radial side. The graft
      was passed through the tunnel in the triquetrum, tightened up and inserted in the
      groove on the lunate, and sutured to the anchor. The rest of the tendon was
      reinserted to the ECU tendon. After suturing the dorsal structures and skin, a
      high plaster cast reaching up above the elbow was applied for 4 weeks, followed
      by application of a short plaster splint for another 2 weeks. RESULTS: Using the
      method of Green and O'Brien, we assessed pain, function (return to full
      activity), range of motion and grip strength. An excellent result was recorded in
      48%, good in 42% and satisfactory in 10% of the patients; there were no poor
      results. DISCUSSION: Our method gives better results than the published methods
      of tenodesis, because it secures stability of both the triquetrum and lunate
      bones. Also, these methods restrict motion to a lesser degree than LTq joint
      arthrodesis. CONCLUSIONS: LTq instability of the wrist is a limiting condition
      for the patient's daily activities. It appears when, for gripping, the hand is
      positioned in dorsal flexion and ulnar duction. The diagnosis and therapy are
      complicated and only arthroscopy is reliable for LTq instability detection. The
      method described here provides an option for treating this disorder with good
      outcome and, in case of failure, does not interfere with a subsequent LTq joint
      arthrodesis.

PMID- 19595283
TI  - [Tendon-splitting approach for the surgical treatment of Haglund's deformity and
      associated condition. Evaluation and results].
AB  - PURPOSE OF THE STUDY: To evaluate the results of the dorsal longitudinal tendon
      splitting approach for surgical treatment of Haglund's deformity and associated
      conditions. MATERIAL: The group comprised patients who underwent surgery for
      Haglund's deformity and related conditions between January 2003 and June 2007.
      There were 15 patients, six women and nine men, with 17 treated heels (one man
      and one woman had bilateral surgery). METHODS: Using the tendon-splitting
      approach, a prominence of the posteriosuperior border of the calcaneus was
      resected and the associated conditions were treated. The evaluation was based on
      a 1-to-5-degree scale and included the patient's clinical state before and after
      surgery (pain, shoe-wearing and load tolerance), and pre-operative radiography
      (presence of Haglund's deformity, ossification of the Achilles tendon and/or
      adjacent tissues). The study was retrospective. RESULTS: The average age of the
      patients at the time of surgery was 44.5 years (range, 16 to 60). The minimum
      follow-up was 6 months (range, 6 to 65 months). X-ray and intra-operative
      findings showed Haglund's deformity in 13 cases, calcaneal bursitis in six,
      ossified mass at the insertion of the Achilles tendon in six, intratendinous
      ossification in two, and partial tendon degeneration and subcutaneous bursitis in
      one case each. Post-operative relief was recorded in 16 treated heels. The
      condition in one patient deteriorated, as manifested by heel swelling after
      exercise and a feeling of tension at the insertion site of the Achilles tendon in
      forced dorsiflexion of the ankle. An average preoperative score of 4.1 improved
      to 2.1 post-operatively. No serious complications either overall or at the site
      of surgery (Achilles tendon rupture, poor wound healing) were found. Three heels
      retained a slight restriction of motion (up to 10 degrees). One heel showed
      impaired sensitivity in the region treated. DISCUSSION: The tendon-splitting
      approach provides a good view of and easy access to the structures to be operated
      on. The risk of incomplete resection of the prominence or of leaving sharp edges
      because of an insufficient view is small. Compared with other methods, this
      approach allows for concurrent treatment of other conditions that may be present
      at the insertion site of the Achilles tendon. The tendon-splitting approach does
      not result in any structural changes of the Achilles tendon. CONCLUSIONS: The
      dorsal longitudinal tendon-splitting approach for surgical treatment of Haglund's
      deformity is an efficient, undemanding and safe method alternative to lateral or
      medial approaches used more often. It allows for concurrent treatment of several
      pathological conditions at the insertion site of the Achilles tendon, such as
      subcutaneous bursitis, ossified mass at the tendon insertion, tendon
      degeneration, intratendinous ossification, calcaneal bursitis and Haglund's
      deformity.

PMID- 19595284
TI  - [Evaluation of screening for developmental dysplasia of the hip in the Liberec
      region in 1984-2005].
AB  - PURPOSE OF THE STUDY: To analyze our results of screening for developmental
      dysplasia of the hip (DDH) in the Liberec region between 1984 and 2005 MATERIAL
      AND METHODS: The study comprised 30,010 infants screened for DDH without any
      primary selection between 1984 and 2005.The infants were clinically examined on
      the basis of a three-step screening system (newborn, at 6 weeks and between 3 and
      4 months of age) and by an imaging method. In the period from 1984 to 1991, this
      was plain radiography of the hip at 3 months of age, and a total of 12,944
      infants were assessed. Between 1992 to 2005 ultrasonography (USG) was used at 6
      weeks (or earlier when clinical signs were present) and again at 3 to 4 months of
      age, and a total of 17,066 infants were evaluated. In 16,678 of these infants,
      the sonogram obtained at 6 weeks was evaluated in detail by the Graf method. The
      presence of the epiphyseal nucleus of the proximal femur was assessed at 3
      months, and from 2000 at 4 months of age. Attention was paid to the occurrence of
      DDH in general and findings of dislocation, both subluxation and luxation, of the
      hip, the proportion of right-side, left-side and bilateral findings, gender
      differences, the presence or absence of ossification of the femoral epiphyseal
      nucleus in infants between 3 and 4 months of age and, in the 1992-2005 period,
      the stratification of Graf types at 6 weeks. A question of whether the child's
      months of birth might have any relation to a possibility of DDH occurrence was
      also raised. RESULTS: Between 1984 and 1991, DDH was recorded in 10.4% of the
      infants, usually in a light form responding well to conservative treatment;
      subluxation was found in 1.99% and luxation in 0.6%. Between 1992 and 2005, DDH
      (mostly light forms) was recorded in 5.2%, subluxation in 0.5% and luxation in
      0.2% of the infants. Right-side, left-side and bilateral findings were seen in
      29%, 46% and 25% of the infants, respectively, and there were distinct
      differences between the genders. In an evaluated group of 453 infants with either
      subluxation or luxation, 86% of girls and 14% of boys were affected. The month of
      birth had no effect on DDH occurrence. Of the 9878 infants examined at 3 months,
      ossification of the femoral epiphyseal nucleus was found only in 37%, and of the
      7188 infants examined at 4 months this was recorded in 64%. In a total of 33,356
      hips (16,678 infants) evaluated at 6 weeks on the Graf scale, the following Graf
      types were recorded: Ia, 21%; Ib, 58%; IIa, 20%; IIc, 1%; D/IIIa, 0.19%; and
      IIIb/IV, 0.08%. DISCUSSION: The occurrence of DDH (formerly congenital dysplasia
      of the hip), including all forms/grades, is reported to be 3% to 5% in Central
      Europe. Our recent results obtained by the USG method are in agreement with this,
      as are our findings of its more frequent occurrence in girls (boys to girls, 1 to
      6) and on the left side. Several reasons--medical, statistical or even
      sociodemographic--can be considered to explain the discrepancies in DDH detection
      rates obtained with radiography and ultrasonography, i.e., 10.5% vs 5.3%. For
      instance, the USG detection of DDH at 6 weeks of age initiates early treatment
      preventing progression of hip dysplasia. Better facilities available for home
      neonatal care and increased interest in general baby wellness may also play a
      role. CONCLUSIONS: Screening for developmental dysplasia of the hip is fully
      justified, because DDH prevalence is still high (500 subluxations and 200
      luxations per 100,000 population). However, attention should also be paid to
      reducing factors and conditions that may adversely affect hip development from
      the baby's prenatal period to spontaneous walking.

PMID- 19595285
TI  - [Calcareous tendinitis of the shoulder. Treatment by needling].
AB  - PURPOSE OF THE STUDY: Calcareous tendinitis (calcifying tendinitis) of the
      shoulder is a disease characterized by the formation of macroscopic deposits of
      hydroxyapatite (a crystalline calcium phosphate) in any tendon of the rotator
      cuff. It presents clinically as sudden intense pain flares resembling gout. It
      can be treated most effectively by invasive methods such as surgery or needling.
      The latter is associated with lower risks and fewer organizational and financial
      demands. The aim of this study is to promote the use of needling in orthopaedic
      outpatient departments where ultrasonography is available for diagnosis and
      guided intervention. MATERIAL: In the period from 2000 to 2006, a total of 38
      shoulders (36 patients) with calcareous tendinitis were treated. In one patient
      both shoulders were effected five years apart, and one patient experienced
      recurrence in the same shoulder after 2 years. Needling was performed in 36
      shoulders, two cases were treated arthroscopically. METHODS: Needling as the
      primary therapy was indicated immediately after the diagnosis had been
      established usually on the first patient's visit, and was carried out under local
      anaesthesia as an outpatient procedure. The tendon with calcareous deposits was
      perforated with a needle under sonographic guidance and, in the majority of
      cases, this calcareous material was aspirated. When signs of subacromial bursitis
      were present, Depomedrol was administered during or following the procedure.
      RESULTS: The outcome was evaluated at an average follow-up of 23.4 months (range,
      5 to 89). All outcomes were from excellent to satisfactory, with no poor result.
      Five patients underwent further treatment for impingement syndrome which two of
      them had already had before the needling procedure. One patient reported slightly
      restricted range of motion due to subsequent adhesive capsulitis. However, she
      was not limited in her daily activities and therefore did not require any further
      therapy. Five patients with occasional unspecific complaints, usually in relation
      to weather changes or exercise, did not ask for any further treatment either.
      CONCLUSIONS: Needling is an effective method to treat calcareous tendinitis and
      provides results comparable with those of arthroscopy, but without operative
      risks. It is much less expensive (10- to 20-times) with no additional demands for
      either the patient or the institution. Today, the majority of orthopaedic
      outpatient departments in the Czech Republic have the necessary facilities and
      should include needling in the procedures routinely performed.

PMID- 19595286
TI  - [Minimally invasive thoracoscopic transdiaphragmatic approach to thoracolumbar
      junction fractures].
AB  - PURPOSE OF THE STUDY: A retrospective analysis of patients with thoracolumbar
      junction fractures who underwent video-assisted thoracoscopic surgery via a
      minimally invasive approach (minithoracotomy) for reconstruction of the anterior
      spinal column. MATERIAL: Between 2002 and 2006, a total of 127 patients were
      treated by this technique. The age of the group, including 75 men and 52 women,
      ranged from 18 to 75 years (average, 45.9 years). L1 and Th12 fractures were
      treated in 71 and 66 patients, respectively. Based on CT scans and operative
      findings, the fractures were assessed as type A in 81, type B in 42 and type C in
      four patients. The causes of injury were a fall from height in 72, a pedestrian's
      fall in 29, a traffic accident in 23 and other in three patients. On admission 19
      patients had a neurological deficit of varying degree: Frankel grade A, eight
      patients; grade B, four; grade C, five; and grade D, two patients. METHODS: The
      patients were treated by either posterior stabilization and, at the second stage,
      the minimally invasive technique via an anterior approach, or the minimally
      invasive anterior procedure alone. Transpedicular posterior stabilization was
      performed in 52 patients. All of them had an anterior procedure completed with
      screw-rod-screw stabilization, and the vertebral body was replaced with an
      allograft or an expandable titanium cage in 50 and two patients, respectively.
      The anterior approach alone was used in 75 patients, who received a bisegmental
      angle-stable implant in 43 and a monosegmental plate in 32 cases. To replace the
      vertebral body, allografts were used in 71 and an expandable titanium cage in
      four patients. RESULTS: The average follow-up period was 3.9 years (range, 1 to 6
      years). In the anterior procedure, the average operative time was 90 min (range,
      50 to 130 min) and blood loss ranged from 200 ml to 2300 ml. A complication due
      to deep infection occurred in one patient and required removal of both the
      anterior and posterior implants. Bony fusion without complications was achieved
      in all patients within a year of surgery. The loss of correction after the
      anterior procedure with an allograft or titanium cage was up to 2 degrees at 1
      year follow-up. No conversion of the minimally invasive technique to a
      conventional approach due to visceral or vascular injury was necessary; nor was
      revision surgery for fluidothorax needed. No loosening of an anterior implant or
      cage dislocation was recorded. Hypesthesia in the operative wound area was found
      in four patients (3.1%). Improvement in neurological status by at least one
      Frankel grade was found in 10 of the 19 affected patients. DISCUSSION: The
      anterior approach is recommended for reconstruction of the anterior spinal column
      in burst fractures of the thoracolumbar junction in particular. An isolated
      posterior approach may result in implant failure during bony union or in the loss
      of correction after implant removal that can lead to the recurrence of kyphosis.
      Conventional thoracotomy is often associated with significant morbidity and hence
      there is a need for a minimally invasive approach to treat thoracolumbar junction
      injury. CONCLUSIONS: The minimally invasive approach (minithoracotomy up to 6-7
      cm) combined with thoracoscopy is an alternative to an exclusively endoscopic
      technique enabling us to provide safe surgical treatment of the anterior spinal
      column.

PMID- 19595287
TI  - [Total hip arthroplasty after femoral neck fracture in patients with acquired
      neurological deficit].
AB  - PURPOSE OF THE STUDY: To evaluate the outcome of total hip arthroplasty (THA)
      performed for femoral neck fracture in patients with a paralytic hip. MATERIAL
      AND METHODS: Between 1997 and 2004, total hip arthroplasty was performed in 301
      patients with a medio-cervical or sub-capital fracture of the femoral neck. In 17
      of them there was also neurological deficit due to a stroke in 11, multiple
      sclerosis in four, and conditions following cranial injury in two. The degree of
      neurological deficit was assessed pre-operatively and its effect on the outcome
      was evaluated, in particular that on the overall results of THA, implant
      stability and post-operative complications. RESULTS: At an average follow-up of
      61 months, 15 out of the 17 patients were examined, because one died and one
      failed to turn up. Four patients had a dislocation and two had a post-operative
      infection and para-articular ossification. Seven patients could walk with the use
      of walking aids, eight had serious difficulties or were in a wheelchair.
      DISCUSSION: The incidence of post-operative complications is much more frequent
      in patients with neurological deficit than in the other THA patients. Some
      possibilities to improve the prospects of neurologically affected patients are
      discussed, such as fall prevention, rational drug therapy, etc. Options for
      operative techniques and implant use are also dealt with as well as post
      operative care to prevent complications. CONCLUSIONS: In patients with medio
      cervical or sub-capital fracture of the femoral neck and co-existent neurological
      deficit, operative considerations should also involve further surgical
      techniques, such as osteosynthesis or Girdlestone arthroplasty. To achieve a good
      outcome it is necessary to choose a correct operative procedure with an optimal
      combination of acetabular and femoral components, to perform additional
      periarticular surgery and to indicate post-operative comprehensive
      rehabilitation.

PMID- 19595288
TI  - [A recurrent or a new infection of total hip replacement? A contribution to the
      discussion on the pathogenesis of prosthetic joint infection].
AB  - In our report we present the case of a 74-year-old man in whom Pseudomonas
      aeruginosa was identified unexpectedly in intra-operative samples taken during a
      one-stage revision total hip arthroplasty (THA). The patient was treated with a
      post-operative, eight-week antibiotic course and, subsequently, was free of
      infectious symptoms. However, 6 years later an infection of his THA was detected
      and Pseudomonas aeruginosa was again isolated. In accordance with traditional
      thinking this should be classified as a new infection, but some recent findings
      on the relationship between the host and infecting bacteria allow us to interpret
      this case as a recurrent infection of THA. It is speculated whether at all, or
      for how long, it is possible for bacteria to survive on the prosthetic surfaces
      without either eliciting the host's immune response or severely damaging the
      surrounding tissues. If it is so, prosthetic joint infection can be understood as
      a disturbed equilibrium between bacteria colonising the implant and the host's
      immune mechanisms, and thus this concept could lead to the development of new
      methods for prevention of this feared THA complication.

PMID- 19595289
TI  - [Frostbite signs versus hyperviscosity syndrome of the lower extremities due to a
      long-term stay at extremely high altitudes].
AB  - PURPOSE OF THE STUDY: The author reports on a case of hyperviscosity syndrome
      resulting from a long-term stay at extremely high altitudes. As a consequence,
      the patient lost the acral parts of the first and second toes on both lower
      extremities.

PMID- 19595290
TI  - [Transoral and cervical approach without mandibulotomy for oropharynx cancer with
      fasciocutaneous radial forearm free flap reconstruction].
AB  - OBJECTIVE: To evaluate the role of a combined transoral and cervical approach
      without mandibulotomy for surgery of oropharyngeal cancer with fasciocutaneous
      radial forearm free flap reconstruction. MATERIAL AND METHODS: All patients who
      underwent this type of surgery between 2003 and 2007 were included in this
      retrospective study. We analyzed postoperative outcomes, surgical margins
      (histological study) and the oncological and functional results. RESULTS: A total
      of 24 patients were included in this study. There was no free flap failure.
      Surgical margins were negative for 23 of the 24 patients. At 3 years, overall,
      cause-specific, and disease-free survival rates were 73, 76 and 68%,
      respectively. A good functional result (normal or slightly impaired function) was
      obtained for oral diet, speech, mouth opening and esthetic outcome in 78, 82, 92
      and 86% of the patients, respectively. CONCLUSION: This double surgical approach
      without mandibulotomy in selective cases can replace the transmandibular approach
      in locally advanced oropharyngeal cancer surgery.

PMID- 19595291
TI  - [Bacteriological study of ethmoid specimens from patients with nasal polyposis
      after ethmoidal surgery].
AB  - OBJECTIVE: To compare the bacteriological and clinical findings in ethmoid
      specimens from patients with nasal polyposis after radical ethmoidal surgery.
      PATIENTS AND METHODS: From June to November 2008, 60 patients were prospectively
      included. For each patient, two samples for each ethmoidal cavity were taken.
      Aerobic and anaerobic bacterial cultures and fungal cultures were processed and
      the antibiotic susceptibility was evaluated for each isolated bacterial strain.
      RESULTS: Pathogenic bacteria were isolated in 48 patients (80%) including
      predominantly Staphylococcus aureus (60%) or a Gram-negative bacterium. The
      microorganisms were nearly all susceptible to antibiotics, including the
      aminoglycosides. No correlation between the presence of pathogenic bacteria and
      the clinical status of the patients was found. CONCLUSION: In this study, a great
      number of patients was colonized with pathogenic bacteria. However, the presence
      of pathogenic bacteria was not correlated with the clinical status of the
      patients.

PMID- 19595292
TI  - A complete task analysis to measure the workload associated with operating an
      agricultural sprayer equipped with a navigation device.
AB  - The objective of this study was to perform a complete task analysis to measure
      the workload associated with operating an agricultural sprayer equipped with a
      navigation device. The task analysis included a written questionnaire and
      subsequent observation of sprayer operators. The questionnaire revealed that the
      lightbar was the most important source of guidance information (as opposed to
      relying on guidance information from external field cues). Observation consisted
      of recording eye-glance behaviour and heart rate variability while operators were
      spraying in a field setting. The eye-glance data suggest that external cues are
      more important than the lightbar for providing the necessary navigation
      information. Thus, the questionnaire and observation data contradict each other.
      Based on heart rate variability, operators who used a lightbar navigation device
      experienced more mental workload than operators who used an auto-steer navigation
      device.

PMID- 19595293
TI  - Evaluation of the remineralizing capacities of modified saliva substitutes in
      vitro.
AB  - OBJECTIVE: In this in vitro study the effects of various calcium and phosphate
      additions to a commercially available saliva substitute on remineralization of
      demineralised dentin were investigated. DESIGN: Bovine dentin specimens (n=70)
      were prepared. Before and after demineralisation (37 degrees C, pH 5.0, 5 days),
      one-quarter of each specimens surface was covered with nail varnish (control
      sound/demineralised tissue). Specimens were exposed either to original Saliva
      natura (SN 0) or to three modified versions (SN 1, SN 2 and SN 3) formulated with
      different degrees of saturation with respect to octacalciumphosphate (OCP) and
      dicalcium phosphate dihydrate (DCPD) for 2 and 5 weeks (37 degrees C). An aqueous
      solution (Buskes remineralizing solution) served as positive control (PC).
      Differences in mineral loss (deltadeltaZ) and lesion depth (deltaLD) before and
      after storage were evaluated from microradiographs. RESULTS: After both storage
      periods dentin specimens immersed in SN 0 revealed significantly higher mineral
      losses (indicated by deltadeltaZ) and higher lesion depths (indicated by deltaLD)
      compared to all other solutions (p<0.05; ANOVA). Specimens stored in SN 1 and 3
      showed significantly higher mineral losses compared with PC (p<0.05). No
      differences could be observed between SN 2 and PC (p>0.05). Only SN 2
      significantly remineralized from 2 to 5 weeks storage (p<0.05; t-test).
      CONCLUSIONS: An experimental Saliva natura solution (SN 2) with S(OCP)=2 and
      S(DCPD)=1.4 showed highest remineralizing capacity. Similar or better
      remineralization could not be achieved with slightly higher or lower saturated
      solutions.

PMID- 19595296
TI  - Multiple organ dysfunction syndrome. Foreword.

PMID- 19595294
TI  - Male eating disorders and therapy: a controlled pilot study with one year follow
      up.
AB  - OBJECTIVES: To examine whether outpatient treatment for male patients with
      bulimic symptomatology is as effective as it is for females. METHOD: The outcome
      of 19 male patients was compared to that of 150 female eating disorder (ED)
      individuals after a group CBT treatment. RESULTS: A reduction in ED
      symptomatology was observed after treatment for both genders. Main effects for
      gender indicated that after collapsing across the mean pre/post values, lower
      mean scores were found for men in the EAT-40, in the EDI-total score and in the
      following EDI subscales: "drive for thinness", "body dissatisfaction" and
      "interoceptive awareness". CONCLUSIONS: A group CBT treatment appears to be
      effective for male and female ED patients.

PMID- 19595295
TI  - Cognitive and affective predictors of treatment outcome in Cognitive Processing
      Therapy and Prolonged Exposure for posttraumatic stress disorder.
AB  - This study examined cognitive and affective predictors of treatment dropout and
      treatment efficacy in Cognitive Processing Therapy (CPT) and Prolonged Exposure
      (PE) for PTSD. Study participants were women with PTSD from a sexual assault who
      received at least one session of either treatment (n = 145) as part of a
      randomized clinical trial. Results revealed that younger age, lower intelligence,
      and less education were associated with higher treatment dropout, whereas higher
      depression and guilt at pretreatment were associated with greater improvement in
      PTSD symptomatology. Results by treatment condition indicated that women with
      higher anger at pretreatment were more likely to dropout of PE and that older
      women in PE and younger women in CPT had the best overall outcomes. These
      findings have implications for efforts to enhance treatment efficacy and
      retention in CBT treatment protocols.

PMID- 19595297
TI  - The multiple organ dysfunction syndrome.

PMID- 19595298
TI  - The crystal structure of a family GH25 lysozyme from Bacillus anthracis implies a
      neighboring-group catalytic mechanism with retention of anomeric configuration.
AB  - Lysozymes are found in many of the sequence-based families of glycoside
      hydrolases (www.cazy.org) where they show considerable structural and mechanistic
      diversity. Lysozymes from glycoside hydrolase family GH25 adopt a
      (alpha/beta)(5)(beta)(3)-barrel-like fold with a proposal in the literature that
      these enzymes act with inversion of anomeric configuration; the lack of a
      suitable substrate, however, means that no group has successfully demonstrated
      the configuration of the product. Here we report the 3-D structure of the GH25
      enzyme from Bacillus anthracis at 1.4A resolution. We show that the active center
      is extremely similar to those from glycoside hydrolase families GH18, GH20, GH56,
      GH84, and GH85 implying that, in the absence of evidence to the contrary, GH25
      enzymes also act with net retention of anomeric configuration using the
      neighboring-group catalytic mechanism that is common to this 'super-family' of
      enzymes.

PMID- 19595299
TI  - Resistance and augmentation of innate immunity in mice exposed to starvation.
AB  - Mice were exposed to starvation for 3 days. Body temperature and various
      parameters were examined. By starvation, body temperature, blood glucose and ACTH
      decreased, especially on days 2 and 3. The level of corticosterone increased at
      this time. On the other hand, the number of lymphocytes yielded by the liver,
      spleen and thymus decreased from day 1 to 3. The change of the distribution of
      lymphocyte subsets was unique because NK, NKT and extrathymic T cells were stress
      resistant in the liver. Conventional T and B cells were stress-sensitive.
      Reflecting the increased proportion of NK and NKT cells, NK and NKT activities
      were augmented. The increased proportion of NKT cells produced both IFNgamma and
      IL-4 (Th0-type profile). The proportion and some functions of granulocytes and
      macrophages increased on Day 1 after starvation. These results suggest that
      starvation has a potential to increase the functions of unconventional
      lymphocytes and myeloid cells.

PMID- 19595301
TI  - New insights into feature and conjunction search: II. Evidence from Alzheimer's
      disease.
AB  - Deficits in inefficient visual search task performance in Alzheimer's disease
      (AD) have been linked both to a general depletion of attentional resources and to
      a specific difficulty in performing conjunction discriminations. It has been
      difficult to examine the latter proposal because the uniqueness of conjunction
      search as compared to other visual search tasks has remained a matter of debate.
      We explored both these claims by measuring pupil dilation, as a measure of
      resource application, while patients with AD performed a conjunction search task
      and two single-feature search tasks of similar difficulty in healthy individuals.
      Maximum pupil dilation in the AD group was greater during performance of the
      conjunction than the feature search tasks, although pupil response was
      indistinguishable for the three tasks in healthy controls. This, together with
      patients' false positive errors for the conjunction task, indicates an AD
      specific deficit impacting upon the ability to combine information on multiple
      dimensions. In addition, maximum pupil dilation was no less for patients than the
      control group during task performance, which tends to oppose the concept of
      general resource depletion in AD. However, eye movement patterns in the patient
      group indicated that they were less able than controls to use organised
      strategies to assist with task performance. The data are therefore in keeping
      with a loss of access to resource-saving strategies, rather than a loss of
      resources per se, in AD. Moreover they demonstrate an additional processing
      mechanism in performing conjunction search compared with inefficient single
      feature search.

PMID- 19595300
TI  - Phenotypic differences between mice deficient in XIAP and SAP, two factors
      targeted in X-linked lymphoproliferative syndrome (XLP).
AB  - Mutations in the X-linked inhibitor of apoptosis (XIAP) have recently been
      identified in patients with the rare genetic disease, X-linked
      lymphoproliferative syndrome (XLP), which was previously thought to be solely
      attributable to mutations in a distinct gene, SAP. To further understand the
      roles of these two factors in the pathogenesis of XLP, we have compared mice
      deficient in Xiap with known phenotypes of Sap-null mice. We show here that in
      contrast to Sap-deficient mice, animals lacking Xiap have apparently normal NKT
      cell development and no apparent defect in humoral responses to T cell-dependent
      antigens. However, Xiap-deficient cells were more susceptible to death upon
      infection with the murine herpesvirus MHV-68 and gave rise to more infectious
      virus. These differences could be rescued by restoration of XIAP. These data
      provide insight into the differing roles of XIAP and SAP in the pathogenesis of
      XLP.

PMID- 19595302
TI  - Plagiarism.

PMID- 19595303
TI  - High bone matrix turnover predicts blood levels of lead among perimenopausal
      women.
AB  - Skeletal bone is the primary endogenous source of lead in circulating blood,
      particularly under conditions of accelerated bone turnover and mineral loss, such
      as pregnancy and postmenopausal osteoporosis. We studied the influence of bone
      turnover rate on the release of lead from bone in 1225 female farmers from 5
      districts in Japan. We collected peripheral blood and urine samples and medical
      nutritional information, and measured forearm bone mineral density (BMD). We
      found that blood lead levels in perimenopausal women were highest among all
      groups studied. Analysis of data for subjects grouped by level of markers of bone
      metabolism suggested that, in perimenopausal women, blood lead levels were higher
      in groups with high levels of N-telopeptide cross-linked collagen type I (NTx)
      and high levels of bone-specific alkaline phosphates (BALP) or osteocalcin (OC)
      compared with groups with low NTx and low BALP or OC levels. Linear multivariate
      models showed that markers of bone turnover were significantly positively related
      to blood lead levels. These results provide evidence that high bone turnover
      rates increase the release of lead stored in bone into the circulation. It is
      likely that markers of bone metabolism can be used to predict blood lead levels.

PMID- 19595304
TI  - Multiple metals predict prolactin and thyrotropin (TSH) levels in men.
AB  - Exposure to a number of metals can affect neuroendocrine and thyroid signaling,
      which can result in adverse effects on development, behavior, metabolism,
      reproduction, and other functions. The present study assessed the relationship
      between metal concentrations in blood and serum prolactin (PRL) and thyrotropin
      (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among
      men participating in a study of environmental influences on male reproductive
      health. Blood samples from 219 men were analyzed for concentrations of 11 metals
      and serum levels of PRL and TSH. In multiple linear regression models adjusted
      for age, BMI and smoking, PRL was inversely associated with arsenic, cadmium,
      copper, lead, manganese, molybdenum, and zinc, but positively associated with
      chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited
      studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo)
      remained when additionally considering multiple metals in the model. Lead and
      copper were associated with non-monotonic decrease in TSH, while arsenic was
      associated with a dose-dependent increase in TSH. For arsenic these findings were
      consistent with recent experimental studies where arsenic inhibited enzymes
      involved in thyroid hormone synthesis and signaling. More research is needed for
      a better understanding of the role of metals in neuroendocrine and thyroid
      function and related health implications.

PMID- 19595305
TI  - Ras signaling and therapies.
AB  - More than 25 years have passed since activating mutations in Ras genes were
      identified in DNA from human tumors. In this time, it has been established beyond
      doubt that these mutations play a direct role in causing cancer, and do so in
      collaboration with a number of other oncogenes and tumor suppressors. Oncogenic
      mutant Ras proteins are resistant to downregulation by GAP-mediated hydrolysis of
      bound GTP, and therefore signal persistently. Efforts to develop therapies that
      block Ras oncoprotein function directly have failed. The high affinity of Ras
      proteins for GTP has discouraged attempts to identify GTP-analogs. Ras processing
      enzymes have been targeted, but unfortunately, K-Ras, the Ras protein that plays
      the major role in human cancer, has proven refractory to these approaches.
      Further progress has been made with drugs that block downstream signaling: the
      approved drug Sorafenib inhibits Raf kinase, and its clinical benefits in liver
      cancer are greatest in patients in which the mitogen activated protein kinase
      (MAPK) signaling pathway is hyperactive. Other Raf kinase inhibitors, as well as
      drugs that block mitogen-activated protein kinase / extracellular signal
      regulated kinase kinase (MEK) and various steps in the PI 3' kinase pathway, are
      under development. Here we will discuss the complexities of Ras signaling and
      their effects on targeting the Ras pathway in the future.

PMID- 19595307
TI  - Tumor dormancy and metastasis.
AB  - Metastasis--the spread of cancer to distant organs--is responsible for most
      cancer deaths. Current adjuvant therapy is based on prognostic indicators that
      stratify patients into defined risk groups. However, some patients believed to
      have a good prognosis nonetheless develop metastases, in some cases many years
      after apparently successful treatment of their primary cancer. This period of
      clinical dormancy leads to many questions about how best to manage patients,
      including how to better assign risk of late recurrence, how long to monitor
      patients, and whether some patients will benefit from extended therapy to prevent
      late recurrences. The development of targeted therapies with fewer side effects
      is leading to clinical trials aimed at determining the effectiveness of such long
      term therapy. However, much remains to be learned about tumor dormancy.
      Experimental studies are shedding light on biological and molecular mechanisms
      potentially responsible for tumor dormancy. Emerging research into tumor
      initiating cells, immunotherapy, and metastasis suppressor genes, may lead to new
      approaches for targeted antimetastatic therapy to prolong tumor dormancy. An
      improved understanding of tumor dormancy is needed for better management of
      patients at risk for late-developing metastases.

PMID- 19595309
TI  - Sirtuins and p53.
AB  - The role of sirtuins in cancer has recently stimulated both considerable interest
      and debate. It is becoming clear that some sirtuins deacetylate important tumor
      suppressors thereby impinging on their activity. Human SirT1, for instance, has
      been shown to deacetylate p53 in biochemical assays, and growing evidence
      indicates that it also performs this activity in cells. Since deacetylation of
      p53 correlates with a decreased p53 transcriptional function, it is conceivable
      that sirtuin inhibition could lead to improved tumor suppression. There are,
      however, still many open questions regarding, for example, whether sirtuins
      deacetylate those lysine residues in p53 that are critical for its activity.
      Preliminary observations also suggest that sirtuin-mediated modulation of p53 can
      also take place indirectly through changes in cellular processes (e.g., nucleolar
      function and p300 activity) known to affect p53. It also remains unclear whether
      depletion in the activity of a single sirtuin suffices to stabilize and activate
      p53 substantially or additional changes in other factors (including other
      sirtuins) are required. Finally, data from SIRT1-knockout mice demonstrate that
      sustained depletion of SirT1 can give rise to genomic instability and that,
      therefore, SirT1 acts as a tumor suppressor. This observation implies that the
      safety of therapeutic interventions based on SirT1 inhibition need to be
      evaluated. Here we review and examine the available data on the regulation of p53
      by sirtuins and on the changes in sirtuin function in tumor cells, and discuss
      whether pharmacological inhibition of sirtuin activity constitutes an adequate
      approach for cancer treatment.

PMID- 19595310
TI  - Oxidative stress and lymphocyte persistence: implications in immunotherapy.
AB  - CD8(+) T cells respond to antigen stimulation through a process of activation,
      division, and differentiation generating a large pool of activated effector
      cytolytic T lymphocytes (CTLs). Many cancer patients harbor the accordant
      precursor CTLs capable of responding to various tumor-associated antigens (TAA).
      In selected cases, vaccination with these TAA can elicit detectable antitumor
      responses. Presently, the clinical outcome of cancer vaccination remains
      inadequate. The lack of clinical efficacy may be attributed to various molecular
      and cellular mechanisms developed by tumors to successfully evade the host immune
      system. Some of these mechanisms have been identified. It is becoming
      increasingly apparent that immunotherapy with the sole objective of inducing
      immune activation is in itself not sufficient to fully overcome the mechanisms
      averting efficient antitumor responses. Strategies to neutralize tumor-induced
      immune suppression have to be developed in parallel to antigenic stimulation. Our
      data show that both oxidative stress- and antigen-mediated preferential cell
      death of antigen-experienced memory CTLs may be a major contributor to tumor
      induced immune dysfunction. The persistence of functional CTLs is a key element
      for an efficient antitumor response and affects the outcome of any immunotherapy
      protocol. We therefore propose that protecting CTLs from premature death by
      identifying and targeting the responsible pathway can lead to substantial
      enhancement in antitumor response. In this review, we discuss some of the
      fundamental factors that may be involved in the modulation of the different
      lymphocyte subsets towards sensitization or resistance to tumor-induced stress.

PMID- 19595311
TI  - Peptic ulcer bleeding outcomes adversely affected by end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) and peptic ulcer disease
      (PUD) bleeding may be at high risk of bleeding complications. OBJECTIVE: To
      investigate the outcomes of patients with ESRD and PUD bleeding. DESIGN: ESRD
      patients with PUD bleeding were evaluated retrospectively. SETTING: Two tertiary,
      university-affiliated hospitals. PATIENTS: A total of 150 PUD bleeding patients
      were evaluated in 3 groups; end-stage renal disease (ESRD) patients on dialysis
      (ESRD group) (n = 50) were age matched with patients with chronic kidney disease
      (CKD) not requiring dialysis (CKD group) (n = 50) and those with normal kidney
      function (normal group) (n = 50). MAIN OUTCOME MEASUREMENTS: Rebleeding,
      transfusions, length of hospitalization, mortality. RESULTS: Multivariate
      analysis showed significant predictors of rebleeding to be ESRD and high-risk
      stigmata. The ESRD group had an odds ratio (OR) of 3.8 (95% CI, 1.4-10.5; P =
      .008) for rebleeding compared with the normal group, and an OR of 3.8 (95% CI,
      1.4-10.3; P = .01) compared with the CKD group. The mean number of (+/- SD)
      transfusions was higher in the ESRD group (6.3 +/- 5.7 units) than in the normal
      group (3.6 +/- 3.9 units; P = .01). The mean length of hospitalization was higher
      in the ESRD group than in the normal group (34.0 vs 16.6 days; P = .01). A
      greater level of comorbidity was the only significant predictor of mortality (OR
      6.0; 95% CI, 2.9-12.3; P = .001). LIMITATION: Retrospective study. CONCLUSION:
      ESRD dialysis patients with PUD bleeding have greater rebleeding than patients
      not on dialysis. ESRD patients should be managed as a high-risk group.

PMID- 19595306
TI  - PI3K/PTEN signaling in angiogenesis and tumorigenesis.
AB  - Phosphatidylinositol 3-kinase (PI3K) and phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN) signaling pathway play an important role in multiple
      cellular functions such as cell metabolism, proliferation, cell-cycle
      progression, and survival. PI3K is activated by growth factors and angiogenesis
      inducers such as vascular endothelial growth factor (VEGF) and angiopoietins. The
      amplification and mutations of PI3K and the loss of the tumor suppressor PTEN are
      common in various kinds of human solid tumors. The genetic alterations of
      upstream and downstream of PI3K signaling molecules such as receptor tyrosine
      kinases and AKT, respectively, are also frequently altered in human cancer. PI3K
      signaling regulates tumor growth and angiogenesis by activating AKT and other
      targets, and by inducing HIF-1 and VEGF expression. Angiogenesis is required for
      tumor growth and metastasis. In this review, we highlight the recent studies on
      the roles and mechanisms of PI3K and PTEN in regulating tumorigenesis and
      angiogenesis, and the roles of the downstream targets of PI3K for transmitting
      the signals. We also discuss the crosstalk of these signaling molecules and
      cellular events during tumor growth, metastasis, and tumor angiogenesis. Finally,
      we summarize the potential applications of PI3K, AKT, and mTOR inhibitors and
      their outcome in clinical trials for cancer treatment.

PMID- 19595312
TI  - Use of a new jumbo forceps improves tissue acquisition of Barrett's esophagus
      surveillance biopsies.
AB  - BACKGROUND: The major risk factors for the development of esophageal
      adenocarcinoma remain long-standing GERD and resultant Barrett's esophagus (BE).
      Finding the exact method of adequate tissue sampling for surveillance of
      dysplasia in BE remains a dilemma. OBJECTIVE: We prospectively compared standard
      large-capacity biopsy forceps with a new jumbo biopsy forceps for dysplasia
      detection in BE. SETTING/DESIGN: Prospective, single-center investigation.
      PATIENTS/INTERVENTIONS: We prospectively enrolled 32 patients undergoing
      surveillance endoscopy for BE. Biopsy samples were obtained in paired fashion
      alternating between the experimental (jumbo) and control (large-capacity)
      forceps. MAIN OUTCOME MEASUREMENTS: Each sample was assessed for histopathology,
      specimen size, and adequacy. RESULTS: A total of 712 specimens were available for
      analysis for this investigation. Six patients were found to have dysplasia, and
      in 5 of those patients, the dysplasia was only detected with the jumbo forceps.
      The mean width was significantly greater in the Radial Jaw 4 jumbo group (3.3 mm
      vs 1.9 mm [P < .005]) as was the mean depth (2.0 mm vs 1.1 mm [P < .005]).
      Sixteen percent of samples obtained with the standard forceps provided an
      adequate sample, whereas the jumbo forceps provided an adequate sample 79% of the
      time (P < .05). LIMITATIONS: A lack of a validated index for assessment of tissue
      adequacy in BE. CONCLUSION: The Radial Jaw 4 jumbo biopsy forceps significantly
      improves dysplasia detection and adequate tissue sampling in patients undergoing
      endoscopy for BE.

PMID- 19595313
TI  - Hyperplastic polyposis syndrome: a pilot study for the differentiation of polyps
      by using high-resolution endoscopy, autofluorescence imaging, and narrow-band
      imaging.
AB  - BACKGROUND: Endoscopic differentiation and removal of potentially premalignant
      sessile serrated adenomas (SSAs) may be important steps in preventing the
      development of colorectal cancer in hyperplastic polyposis syndrome (HPS).
      OBJECTIVE: To assess the value of high-resolution endoscopy, autofluorescence
      imaging (AFI), and narrow-band imaging (NBI) for differentiating polyps in HPS.
      DESIGN: A prospective polyp series. SETTING: Single tertiary referral center.
      PATIENTS AND INTERVENTIONS: Seven patients with HPS underwent colonoscopy with
      endoscopic trimodal imaging, which incorporates high-resolution endoscopy, AFI,
      and NBI in 1 system. All detected polyps were analyzed with AFI for color and
      with NBI for Kudo pit pattern and vascular pattern intensity. MAIN OUTCOME
      MEASUREMENTS: The accuracy, sensitivity, and specificity of AFI and NBI in
      differentiating detected polyps were determined by using histology as the
      criterion standard. RESULTS: A total of 19 hyperplastic polyps (HPs), 32 SSAs,
      and 15 adenomas were detected. For differentiating SSAs from HPs, AFI color, Kudo
      pit pattern, and vascular pattern intensity resulted in a diagnostic accuracy of
      55%, 55%, and 52%, respectively. For differentiating adenomas from HPs, the
      accuracy was 65%, 94%, and 90%, respectively. Macroscopically, the combination of
      a size of 3 mm or larger and a proximal location resulted in the highest accuracy
      (76%) for differentiating SSAs from HPs. LIMITATION: Small sample size.
      CONCLUSION: Endoscopic differentiation between HPs and SSAs by using endoscopic
      trimodal imaging proved unsatisfactory. Differentiation of adenomas from HPs was
      possible with NBI but not with AFI.

PMID- 19595314
TI  - Asymptomatic intussusception secondary to a giant appendiceal mucocele treated
      via a laparoscopic approach.

PMID- 19595308
TI  - Histone demethylases and cancer.
AB  - Epigenetic modifications are heritable chromatin alterations that contribute to
      the temporal and spatial interpretation of the genome. The epigenetic information
      is conveyed through a multitude of chemical modifications, including DNA
      methylation, reversible modifications of histones, and ATP-dependent nucleosomal
      remodeling. Deregulation of the epigenetic machinery contributes to the
      development of several pathologies, including cancer. Chromatin modifications are
      multiple and interdependent and they are dynamically modulated in the course of
      various biological processes. Combinations of chromatin modifications give rise
      to a complex code that is superimposed on the genetic code embedded into the DNA
      sequence to regulate cell function. This review addresses the role of epigenetic
      modifications in cancer, focusing primarily on histone methylation marks and the
      enzymes catalyzing their removal.

PMID- 19595315
TI  - Simultaneous confocal laser endomicroscopy and chromoendoscopy with topical
      cresyl violet.
AB  - BACKGROUND: Confocal laser endomicroscopy (CLE) has been shown to reliably
      predict histology during ongoing endoscopy. To unmask lesions for CLE,
      chromoendoscopy has been mandated. Usually fluorescein then serves as a contrast
      agent for CLE, but it does not allow direct nuclear visualization, must be
      injected, leads to a transient skin discoloration, and may have allergic side
      effects. OBJECTIVE: To establish a single topical dye, cresyl violet (CV), for
      simultaneous chromoendoscopy and in vivo CLE of the lower GI tract. DESIGN:
      Animal preclinical study, prospective clinical trial. SETTING: Mainz University
      Clinic (tertiary care center). PATIENTS, METHODS, AND INTERVENTIONS: To establish
      the staining characteristics and optimal concentration of CV, the ileum and colon
      of 7 BL6 mice were stained with CV (0.1%-2%), and in vivo confocal imaging was
      performed with FIVE1. In a subsequent clinical trial, 67 sites in 36 patients
      were topically stained with CV 0.13%, and subsurface serial images were generated
      at different depths with an endomicroscope. MAIN OUTCOME MEASUREMENTS: Prediction
      of histology according to the Mainz confocal classification and nuclear
      visualization with topical CV. RESULTS: Endomicroscopy with topical CV yielded
      (sub-)cellular details of normal mucosa, and regenerative and neoplastic changes
      at variable imaging depths in high resolution comparable to those with
      intravenous fluorescein. By cytoplasmic enrichment of CV, nuclear morphology
      could be negatively visualized. Reliable differentiation of nonneoplastic versus
      neoplastic changes during ongoing endoscopy and a high interobserver agreement
      based on the microscopic images generated in vivo could be achieved. LIMITATIONS:
      Single-center study, nonrandomized, limited number of patients. CONCLUSIONS: CV
      can be applied topically and allows simultaneous chromoendoscopy and
      endomicroscopy with accurate prediction of histology with visualization of
      nuclear morphology. It may therefore be a single-agent alternative to
      chromoendoscopy and fluorescein in endomicroscopy.

PMID- 19595316
TI  - Natural orifice imaging of the abdominal wall.

PMID- 19595317
TI  - Massive hemobilia during extraction of a covered self-expandable metal stent in a
      patient with portal hypertensive biliopathy.

PMID- 19595318
TI  - Trimodal imaging endoscopy may improve diagnostic accuracy of early gastric
      neoplasia: a feasibility study.
AB  - BACKGROUND: A considerable number of superficial gastric neoplasias are
      overlooked with conventional white light imaging (WLI) endoscopy. OBJECTIVE: The
      aim was to investigate the diagnostic potential of trimodal imaging endoscopy
      (TME), which combines WLI, autofluorescence imaging (AFI), and narrow-band
      imaging (NBI), for superficial gastric neoplasia. DESIGN: Feasibility study.
      SETTING: Single academic center. PATIENTS: Sixty-two patients with or without
      gastric neoplasia. INTERVENTION: Each patient serially assessed with WLI, AFI,
      and magnifying endoscopy with NBI (ME-NBI) by an endoscopist blinded for clinical
      information. ME-NBI over WLI and AFI was designated as TME. Histopathology of
      biopsy and ESD specimens was evaluated and used as the gold standard. MAIN
      OUTCOME MEASUREMENTS: Sensitivity and specificity of endoscopic diagnosis of
      pathology-proven neoplasia by per-patient and per-lesion analyses. RESULTS: The
      study included 47 pathology-proven neoplasias and 44 pathology-proven
      nonneoplasias that were detected as neoplasias with any of the modalities. By a
      per-lesion analysis, the sensitivity of TME (89.4%) was higher than that of WLI
      (76.6%) and AFI (68.1%). The specificity of TME (98.0%) was higher than that of
      WLI (84.3%) and AFI (23.5%). By a per-patient analysis, the sensitivity of TME
      (90.9%) was higher than that of WLI (75%) and AFI (68.2%). The specificity of TME
      (100%) was higher than that of WLI (72.2%) and AFI (44.4%). LIMITATIONS: Case
      enriched population at a single center. CONCLUSIONS: Higher diagnostic accuracy
      of TME over conventional WLI indicates the feasibility of TME for the efficacious
      diagnosis of early gastric neoplasia.

PMID- 19595319
TI  - Combined endoscopic stent-in-stent placement for malignant biliary and duodenal
      obstruction by using a new duodenal metal stent (with videos).
AB  - BACKGROUND: Self-expandable metal stents (SEMSs) are an effective palliative
      treatment for malignant biliary or duodenal strictures, but endoscopic stenting
      for combined malignant biliary and duodenal obstruction remains technically
      difficult. OBJECTIVE: To evaluate the feasibility and clinical success rate of
      endoscopic double stent-in-stent placement by using a new duodenal metallic stent
      for the management of malignant biliary and duodenal obstructions. DESIGN:
      Prospective, observational clinical feasibility study. SETTING: Tertiary referral
      center. MAIN OUTCOME MEASUREMENT: Technical and clinical success, complications,
      midterm outcome. PATIENTS AND METHODS: Eight patients with inoperable malignant
      biliary and duodenal strictures were enrolled. Endoscopic placement of a biliary
      SEMS was performed through the mesh of the duodenal stent. RESULTS: The duodenal
      strictures were in the first part of the duodenum in 3 patients (type 1) and in
      the second part in 5 patients (type 2). Duodenal stents were successfully
      deployed in all patients. Endoscopic placement of a biliary SEMS through the mesh
      of the duodenal stent was successful in 7 (87.5%) of 8 patients. In 2 of 3
      patients with type 2 duodenal strictures with failed bile duct cannulation,
      biliary stenting was successful by using the rendezvous procedure. Early
      complications occurred in 1 patient. The overall median survival after combined
      stenting was 91 days (range 36-314 days). LIMITATIONS: Small number of patients
      and no comparison with other enteral stents. CONCLUSIONS: Biliary stenting
      through the new duodenal metallic stent is technically feasible and has a high
      success rate. Combined endoscopic biliary and duodenal stent-in-stent placement
      is a promising solution for the palliation of malignant biliary and duodenal
      obstruction.

PMID- 19595321
TI  - Endogenous and exogenous control of gametogenesis and spawning in echinoderms.
AB  - Most echinoderms display seasonal or other temporal cycles of reproduction that
      presumably result from the complex interplay of endogenous and exogenous signals.
      Various environmental, chemical and hormonal factors, acting directly or
      indirectly, individually or in combination, have been proposed to cue, favour or
      modulate a suite of reproductive functions from the onset of gametogenesis to
      gamete release. From as early as the nineteenth century, an astonishing array of
      studies has been published on topics related to the control of reproduction in
      echinoderms, ranging from fortuitous behavioural observations to complex
      experimental demonstrations and molecular analyses. Although the exact pathways
      involved in the perception of external signals and their transduction into
      coordinated spawning events remain obscure for most species, significant advances
      have been made that shed new light on the information gathered over decades of
      research. By compiling the existing literature (over 1000 references),
      interpreting the main results, critically assessing the methodologies used and
      reviewing the emerging hypotheses, we endeavour to draw a clearer picture of the
      existing knowledge and to provide a framework for future investigation of the
      mechanisms that underlie reproductive strategies in echinoderms and, by
      extension, in other marine invertebrates.

PMID- 19595325
TI  - Removal of erythropoietin from anaemia trauma practice guideline does not
      increase red blood cell transfusions and decreases hospital utilization costs.
AB  - INTRODUCTION: We previously demonstrated that utilization of erythropoietin (r
      EPO) did not significantly reduce blood utilization in trauma patients. We
      undertook this study to analyze blood utilization 1 year after r-EPO removal from
      our trauma service anaemia practice management guideline. METHODS: Electronic
      records of patients admitted to the trauma service were retrospectively reviewed
      for units of packed red blood cells (pRBCs) transfused and for units of r-EPO
      administered 12 months before the initiation of an anaemia practice guideline
      (PRE), 12 months during the use of an anaemia guideline (GUIDE), and 12 months
      following removal of r-EPO from the guideline (POST). Hospital acquisition cost
      was also reviewed for the respective time periods. Nominal data were analyzed
      using chi-squared or Fisher's exact tests, and interval data were compared using
      ANOVA followed by Tukey's test where appropriate. Results were considered
      significant for P<0.05. RESULTS: Over the 3-year study period, 4881 patients were
      admitted to the trauma service and included in this study. The hospital length of
      stay, intensive care unit length of stay, and units of pRBC transfused were
      similar among all three groups. Group I (PRE) received a total of 228 doses of r
      EPO at a cost of $102,600. Group II (GUIDE) received a total of 410 doses at a
      cost of $184,500. Group III (POST) received 28 doses of r-EPO at a cost of
      $12,600. CONCLUSION: Removal of erythropoietin from our trauma service anaemia
      practice management guideline did not result in increased blood utilization.
      However, it yielded a hospital acquisition cost savings of $171,900.

PMID- 19595326
TI  - Factors affecting results of patients with humeral proximal end fractures
      undergoing primary hemiarthroplasty: a retrospective study in 42 patients.
AB  - AIM: Our study reports long-term results and factors related to patient
      satisfaction in the case of primary hemiarthroplasty for humeral proximal end
      fractures. PATIENTS AND METHODS: We retrospectively evaluated 42 patients with
      humeral proximal end fractures who underwent primary hemiarthroplasty in our
      clinic from February 1994 to March 2004. Of the 42 patients, 14 (33%) were male
      and 28 (67%) female. The mean age was 68.9+/-5.57 years (age range: 59-81 years).
      The mean follow-up period was 78.8+/-26.6 months (range: 48-118 months). We
      evaluated the following parameters: fracture type according to the Neer
      classification, the time interval between the fracture and the operation,
      postoperative radiological examination, the Neer outcome assessment criteria for
      patient satisfaction and functions, according to the Constant and Murley Scoring
      (CMS) system. RESULTS: We found good-to-excellent outcomes in 36 (85.7%) and poor
      outcome in six (14.3%) patients according to the Neer criteria. The average
      values for CMS score, anterior elevation and external rotation were 73.59+/-17.95
      (25-94), 121.30+/-42.99 degrees (range: 30-170 degrees ) and 30 degrees (range: 0
      80 degrees ), respectively. The patients who had been operated in the early
      period (within 2 weeks) had better functional outcomes (p<0.001) and had
      significant pain relief. There was a strong positive correlation between the
      humeral offset (distance between the head and the tuberosities) and the degree of
      elevation (r=0.872, p<0.001). There was a strong negative correlation between the
      height of the humeral head and the degree of elevation (r=-0.853, p<0.001).
      CONCLUSION: In humeral proximal end fractures, primary hemiarthroplasty in the
      early period with the anatomic reconstruction of bone and soft tissues of the
      shoulder joint and long-term regular rehabilitation programme are important
      factors contributing to increased patient satisfaction.

PMID- 19595327
TI  - Is dopexamine superior to dopamine in the treatment of multiple trauma patients-
      a prospective, double-blind, randomised study.
AB  - BACKGROUND: The goal of this prospective, randomised, double-blind clinical trial
      study was to assess the effects of dopexamine hydrochloride on organ failure,
      inflammatory mediators and splanchnic oxygenation in blunt multiple trauma
      patients at high risk of multiple organ dysfunction syndrome (MODS). METHODS: We
      performed a prospective randomised controlled trial on 30 consecutive blunt
      multiple trauma patients with ISS>or=16, age 18-60 years and initial blood
      pressure >or=120 mmHg initially admitted to our level I trauma centre. Patients
      were randomised to treatment with dopamine (n=15) or dopexamine (n=15) for 48 h
      after admission. Outcome in terms of mortality, MODS, splanchnic perfusion,
      complications, duration of stay was statistically analysed. RESULTS: Dopexamine
      treatment was associated with impaired organ function and an increased duration
      of ventilation and ICU stay compared with patients who received dopamine
      treatment. The acute inflammatory response was increased in the Dopexamine group
      while a decreased pHi and MEGX formation and increased serum lactate levels were
      measured. CONCLUSIONS: The indication to use dopexamine hydrochloride appears
      questionable. In the absence of an antiinflammatory effect, dopexamine
      demonstrated a disadvantageous ICU course in regards to the organ function and
      the duration of treatment. In addition, a decreased pHi and MEGX formation
      suggested a deterioration of splanchnic oxygenation.

PMID- 19595328
TI  - Fighting river blindness and other ills.

PMID- 19595329
TI  - Addressing severe acute malnutrition where it matters.

PMID- 19595330
TI  - Reporting genetic association studies: the STREGA statement.

PMID- 19595331
TI  - New WHO growth standards: roll-out needs more resources.

PMID- 19595333
TI  - Jonathan Currie.

PMID- 19595334
TI  - Tissue.

PMID- 19595335
TI  - Body-mass index and mortality.

PMID- 19595336
TI  - Body-mass index and mortality.

PMID- 19595337
TI  - Body-mass index and mortality.

PMID- 19595340
TI  - Responsibilities of the President of the World Medical Association.

PMID- 19595341
TI  - Responsibilities of the President of the World Medical Association.

PMID- 19595342
TI  - Sri Lanka: the aftermath.

PMID- 19595343
TI  - Fire-related deaths in India: how accurate are the estimates?

PMID- 19595344
TI  - Sri Lanka: the aftermath.

PMID- 19595345
TI  - Sri Lanka: the aftermath.

PMID- 19595346
TI  - More to evidence than NHS Evidence.

PMID- 19595348
TI  - Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double
      blind efficacy randomised controlled trial in Malawi.
AB  - BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and
      causes 1-2 million deaths every year. Our aim was to assess the clinical and
      nutritional efficacy of a probiotic and prebiotic functional food for the
      treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We
      recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to
      32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised,
      placebo-controlled efficacy trial. For generalisability, all admissions for
      severe acute malnutrition treatment were eligible for recruitment. After
      stabilisation with milk feeds, children were randomly assigned to ready-to-use
      therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte.
      Average prescribed Synbiotic dose was 10(10) colony-forming units or more of
      lactic acid bacteria per day for the duration of treatment (median 33 days).
      Primary outcome was nutritional cure (weight-for-height >80% of National Center
      for Health Statistics median on two consecutive outpatient visits). Secondary
      outcomes included death, weight gain, time to cure, and prevalence of clinical
      symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an
      intention-to-treat basis. This trial is registered as an International Standard
      Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure
      was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3%
      [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV
      seropositivity was associated with worse outcomes overall, but did not modify or
      confound the negative results. Subgroup analyses showed possible trends towards
      reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In
      Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes.
      The observation of reduced outpatient mortality might be caused by bias,
      confounding, or chance, but is biologically plausible, has potential for public
      health impact, and should be explored in future studies. FUNDING: Department for
      International Development (DfID).

PMID- 19595349
TI  - Hyperparathyroidism.
AB  - Hyperparathyroidism is due to increased activity of the parathyroid glands,
      either from an intrinsic abnormal change altering excretion of parathyroid
      hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal
      change affecting calcium homoeostasis stimulating production of parathyroid
      hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third
      most common endocrine disorder, with the highest incidence in postmenopausal
      women. Asymptomatic disease is common, and severe disease with renal stones and
      metabolic bone disease arises less frequently now than it did 20-30 years ago.
      Primary hyperparathyroidism can be cured by surgical removal of an adenoma,
      increasingly by minimally invasive parathyroidectomy. Medical management of mild
      disease is possible with bisphosphonates, hormone replacement therapy, and
      calcimimetics. Vitamin D deficiency is a common cause of secondary
      hyperparathyroidism, particularly in elderly people. However, the biochemical
      definition of vitamin D deficiency and its treatment are subject to much debate.
      Secondary hyperparathyroidism as the result of chronic kidney disease is
      important in the genesis of renal bone disease, and several new treatments could
      help achieve the guidelines set out by the kidney disease outcomes quality
      initiative.

PMID- 19595351
TI  - Bang! The smoker with suprapubic pain.

PMID- 19595350
TI  - Management of occlusion and thrombosis associated with long-term indwelling
      central venous catheters.
AB  - Long-term central venous catheters (CVCs) are important instruments in the care
      of patients with chronic illnesses, but catheter occlusions and catheter-related
      thromboses are common complications that can result from their use. In this
      Review, we summarise management of these complications. Mechanical CVC occlusions
      need cause-specific treatment, whereas thrombotic occlusions usually resolve with
      thrombolytic treatment, such as alteplase. Prophylaxis with thrombolytic flushes
      might prevent CVC infections and catheter-related thromboses, but confirmatory
      studies and cost-effectiveness analysis of this approach are needed. Risk factors
      for catheter-related thromboses include previous catheter infections, malposition
      of the catheter tip, and prothrombotic states. Catheter-related thromboses can
      lead to catheter infection, pulmonary embolism, and post-thrombotic syndrome.
      Catheter-related thromboses are usually diagnosed by Doppler ultrasonography or
      venography and treated with anticoagulation therapy for 6 weeks to a year,
      dependent on the extent of the thrombus, response to initial therapy, and whether
      thrombophilic factors persist. Prevention of catheter-related thromboses includes
      proper positioning of the CVC and prevention of infections; anticoagulation
      prophylaxis is not currently recommended.

PMID- 19595353
TI  - HDL biogenesis and functions: role of HDL quality and quantity in
      atherosclerosis.
AB  - Coronary heart disease (CHD) is a leading cause of death in western societies. In
      the last few decades, a number of epidemiological studies have shown that a
      disproportion between atheroprotective and atherogenic lipoproteins in plasma is
      one of the most important contributors towards atherosclerosis and CHD. Thus,
      based on the classical view, reduced HDL cholesterol levels independently predict
      one's risk factor for developing cardiovascular disease, while elevated HDL
      levels protect from atherosclerosis. However, more recent studies have suggested
      that the relationship between HDL and cardiovascular risk is more complex and
      extends beyond the levels of HDL in plasma. These studies challenge the existing
      view on HDL and cardiovascular risk and trigger a discussion as to whether low
      HDL is a causal effect for the development of heart disease. In this article we
      provide a review of the current literature on the biogenesis of HDL and its
      proposed functions in atheroprotection. In addition, we discuss the significance
      of both HDL quality and quantity in assessing cardiovascular risk.

PMID- 19595352
TI  - Lovastatin inhibits oxidized L-A-phosphatidylcholine B-arachidonoyl-gamma
      palmitoyl (ox-PAPC)-stimulated interleukin-8 mRNA and protein synthesis in human
      aortic endothelial cells by depleting stores of geranylgeranyl pyrophosphate.
AB  - Human aortic endothelial cells (HAEC) exposed to 50 microg/ml oxidized L-A
      phosphatidylcholine B-arachidonoyl-gamma-palmitoyl (ox-PAPC) for 6h increased in
      interleukin-8 mRNA and protein levels. Preincubation of HAEC with the 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG CoA) inhibitor, (20 microM), significantly
      inhibited ox-PAPC-stimulated interleukin-8 mRNA and protein levels. Mevalonate
      (200 microM) reversed the inhibition of ox-PAPC-stimulated mRNA and protein
      levels by lovastatin, indicating the inhibitory effect of lovastatin was due to
      inhibition of mevalonate synthesis. Addition of the geranylgeraniol (GGOL, 10
      microM) but not farnesol (FOL, 10 microM), reversed the inhibitory effect of
      lovastatin on interleukin-8 mRNA and protein levels stimulated by ox-PAPC,
      indicating that lovastatin exerted its effect by inhibiting stores of
      geranylgeranyl pyrophosphate (GGPP) which are necessary for geranylgeranylation
      of proteins. These results suggest a new mechanism for lovastatin in preventing
      atherosclerosis by inhibiting the inflammatory response that takes place in the
      vascular wall.

PMID- 19595354
TI  - Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical
      atherosclerosis in human immunodeficiency virus infected subjects.
AB  - BACKGROUND AND OBJECTIVE: Although anti-retroviral therapy (ART) prolonged
      survival in HIV-infected persons, an increase in cardiovascular disease has also
      been observed. A frequent complication of ART is the development of lipodystrophy
      (LD) with its multiple phenotypes that may be associated with cardiovascular
      disease. We assessed the contribution of chronic HIV infection, ART use and LD to
      the presence of sub-clinical atherosclerosis as evaluated by coronary artery
      calcium (CAC) imaging. METHODS: Observational cross-sectional study of 372 HIV
      infected patients receiving ART who attended a cardiometabolic clinic (48.2+/-8
      year old; 74% men). All patients underwent CAC surveillance with computed
      tomography and the Agatston score was used to quantitate CAC. Presence of CAC was
      defined as a score >10. Multivariable logistic regression was used to evaluate
      associations between HIV clinical factors, ART and LD with the presence of CAC.
      FINDINGS: CAC was found in 134 patients (36%) with a median CAC score of 50
      (range 10; 1243). Lipoatrophy alone (OR 3.82, 95% CI: 1.11; 13.1), fat
      accumulation alone (OR 7.65, 95% CI: 1.71; 37.17) and mixed lipodystrophy
      phenotypes (OR 4.36, 95% CI: 1.26; 15.01) were strongly associated with presence
      of CAC after adjusting for age, sex, hypertension and cumulative exposure to ART.
      CONCLUSION: CAC is common among long-term ART users. The association between CAC
      and LD underscores the potential atherosclerosis risk inherent with ART and the
      need to undertake routine cardiovascular surveillance in patients treated with
      these drugs.

PMID- 19595355
TI  - Characterization of volatile components of Iranian saffron using factorial-based
      response surface modeling of ultrasonic extraction combined with gas
      chromatography-mass spectrometry analysis.
AB  - The volatile components of Iranian saffron were extracted using ultrasonic
      solvent extraction (USE) technique and then were separated and detected by gas
      chromatography-mass spectrometry (GC-MS). Variables affecting the extraction
      procedure were screened by using a 2(5-1) fractional factorial design and among
      them; sample amount, solvent volume, solvent ratio and extraction time were
      optimized by applying a rotatable central composite design (CCD). The optimum
      values of factors were: 2.38g sample, 29.04mL solvent, 69.23% MeOH solvent ratio
      and 71.8min for the extraction time. Forty constituents were identified for
      Iranian saffron by GC-MS representing 90% of the total peak area. The major
      components were 2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, namely
      safranal (26.29%), bicyclo[3,2,0]hept-2-ene-,4-ethoxy-,endo (5.69%), linoleic
      acid (4.77%), 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde, namely
      HTCC (4.44%), and nonadecanol (3.32%). Some new compounds were identified for the
      first time in saffron. In addition, the results of this study were compared with
      those of Greek saffron.

PMID- 19595356
TI  - The validation of methods for regulatory purposes in the control of residues.
AB  - The topic of validation is diversified. This review outlines the validation
      strategies which can be found in national, international and supranational
      regulations, compares them with one another and aims to elaborate on the main
      principles. European regulations and legislation, Codex alimentarius guidelines,
      the official methods program of the AOAC, and naturally the relevant ISO
      standards, particularly the ISO 5725 series, are taken into consideration. The
      objective of every validation is to demonstrate fitness for purpose. This varies
      of course in its characteristics for the diverse uses. However, all approaches
      have in common the objective of harmonisation of food control by using effective
      and reliable methods. To this end, criteria are determined and validation models
      developed and made compulsory. ISO 5725 is the central basis for validations for
      quantitative methods with its validation specifications through method
      collaborative studies. On the contrary, there are no valid uniform international
      method specifications for qualitative methods. Collaborative studies are in
      opposition to single-lab-validations with different sources of error. Whereas
      laboratory errors are predominant in collaborative studies, the single-lab
      validation or in-house validation concentrates particularly on time and
      processing errors (intermediate precision). In new statistical models for in
      house validations, the matrix mismatch error is also considered. The validation
      models presented here are of a general nature and can be used in principle for
      all analytical methods. Correct and appropriate statistical modelling is very
      important.

PMID- 19595357
TI  - Interconnected porous epoxy monoliths prepared by concentrated emulsion
      templating.
AB  - Porous epoxy monoliths were prepared via a step polymerization in a concentrated
      emulsion stabilized by non-ionic emulsifiers and colloidal silica. A solution in
      4-methyl-2-pentanon was used as the continuous phase, which contained glycidyl
      amino epoxy monomer (GAE), curing agent, and an emulsifier. An aqueous suspension
      of colloidal silica was used as the dispersed phase of the concentrated emulsion.
      After the continuous phase was completely polymerized, the dispersed phase was
      removed and a porous epoxy was obtained. An optimal HLB value of emulsifier for
      the GAE concentrated emulsion was determined. In addition, the morphology of the
      porous epoxy was observed by SEM. The effect of the colloidal silica, the
      emulsifier, the curing of the epoxy, and the volume fraction of the dispersed
      phase on the morphology of porous epoxy are systematically discussed.

PMID- 19595358
TI  - Brownian dynamics simulations of a dispersion composed of two-types of spherical
      particles: for development of a new technology to improve the visibility of
      rivers and lakes.
AB  - We have carried out Brownian dynamics simulations of sedimentation phenomena of a
      dispersion composed of two-kinds of spherical particles under the gravity field.
      This study may be the first step to develop a new technology which enables us to
      improve the visibility of rivers and lakes. In the present study, we have modeled
      sub-micrometer-dimension particles, or dirty particles, as small spherical
      particles, and capturing particles as large spherical particles; these two-kinds
      of particles conduct Brownian motion in water, and large particles adsorb small
      particles to sediment gradually toward the bottom in the gravity field. From the
      results of simulations, the influences of Brownian motion, the size of each
      particle, and the gravity force on the performance of the adsorption of large
      particles have been discussed. In addition, we have discussed what the most
      appropriate situation of large particles is to accomplish the most effective
      adsorption rate or improve the visibility of water most effectively in terms of
      capturing particles. The most important conclusion derived from the present
      results is that, in order to improve the capturing performance, the Brownian
      motion of large particles has to be activated in an appropriate number density
      without losing the influence of the gravity.

PMID- 19595359
TI  - Influence of hydrophilic surfactants on the properties of multiple W/O/W
      emulsions.
AB  - Multiple W/O/W emulsions for topical application using Span 80 as a lipophilic
      emulsifier were prepared. Several hydrophilic emulsifiers were tested in respect
      of their suitability for the preparation of multiple emulsions. In addition, the
      effect of different oil-phase compositions on emulsion stability was
      investigated. The physicochemical parameters of the formulations were
      characterized and their long-term stability was evaluated by means of rheological
      measurements, droplet size observations and conductivity analysis. As discovered,
      the modification of an oil-phase composition results in a decrease in the
      diffusion coefficient of water and water-soluble substances and, consequently, in
      enhanced stability. The influence of the release of electrolytes from the inner
      to the outer water phase on the emulsion stability behaviour was investigated. It
      was found, that the effect of the hydrophilic emulsifiers on the formulation
      properties is related not only to its HLB value, but rather to its chemical
      composition. As a result, polyethoxylated ethers of fatty alcohols (C=16-18) with
      HLBs between 15.3 and 16.2 appear to be the most suitable ones for creating
      stable formulations.

PMID- 19595360
TI  - Fever in returned travellers presenting in the United Kingdom: recommendations
      for investigation and initial management.
AB  - International travel is increasing. Most physicians and general practitioners
      will encounter returned travellers with fever and the majority of travel-related
      infection is associated with travel to the tropics. In those returning from the
      tropics malaria must always be excluded, and HIV considered, from all settings.
      Common causes of non-malarial fever include from Africa rickettsial diseases,
      amoebic liver abscess and Katayama syndrome; from South and South East Asia,
      enteric fever and arboviral infection; from the Middle East, brucellosis and from
      the Horn of Africa visceral leishmaniasis. Other rare but important diseases from
      particular geographical areas include leptospirosis, trypanosomiasis and viral
      haemorrhagic fever. North and South America, Europe and Australia also have
      infections which are geographically concentrated. Empirical treatment may have to
      be started based on epidemiological probability of infection whilst waiting for
      results to return. The evidence base for much of the management of tropical
      infections is limited. These recommendations provide a pragmatic approach to the
      initial diagnosis and management of fever in returned travellers, based on
      evidence where it is available and on consensus of expert opinion where it is
      not. With early diagnosis and treatment the majority of patients with a
      potentially fatal infection related to travel will make a rapid and full
      recovery.

PMID- 19595361
TI  - Significance of T-wave amplitude and dynamics at the time of reperfusion in
      patients with acute ST-segment elevation myocardial infarction treated with
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Peri-interventional T-wave changes may reflect the microvascular
      reperfusion status and potentially carry early independent, prognostic
      information in patients with ST-elevation myocardial infarction (STEMI) treated
      with primary percutaneous coronary intervention (PCI). METHODS: The first
      available electrocardiogram (ECG) (index ECG) and the ECG recorded immediately
      post-PCI were analyzed for T-wave morphology in 207 patients with STEMI. Absolute
      T-wave amplitude was recorded and any change in T-wave amplitude from index ECG
      to post-PCI ECG was calculated. Continuous ST monitoring was performed from
      hospital arrival until 90 minutes after PCI. Maximum troponin level and left
      ventricular ejection fraction were evaluated before discharge. Final infarct size
      was assessed by myocardial perfusion imaging after 1 month. RESULTS: Large,
      positive T-wave amplitude in the index ECG and the post-PCI ECG was associated
      with delayed ST resolution after PCI. In the post-PCI ECG, T-wave amplitude was
      positively associated with troponin-T value (P < .001) and final infarct size (P
      = .036), and inversely associated with left ventricular ejection fraction (P <
      .001). However, T-wave amplitude in the post-PCI ECG was also associated with
      procedural increase in ST elevation (P < .001) and inversely associated with
      spontaneous ST resolution (P < .017). A net decrease in T-wave amplitude during
      reperfusion therapy was associated with faster microvascular reperfusion as
      evaluated by time to ST resolution. CONCLUSION: Large T-wave amplitudes in static
      pre- and post-PCI ECGs are associated with delayed microvascular reperfusion,
      whereas the dynamic development of more negative T waves during PCI is associated
      with earlier microvascular reperfusion. However, in the acute setting, T waves
      provide little incremental information when compared to ST parameters available
      in the per-interventional phase.

PMID- 19595362
TI  - Impact of the American College of Cardiology/American Heart Association
      guidelines for interpretability of continuous electrocardiography on the
      association of silent ischemia with troponin release after major noncardiac
      surgery.
AB  - INTRODUCTION: Preexisting electrocardiographic abnormalities may limit accuracy
      of continuous electrocardiography (cECG) for ischemia determination. The American
      College of Cardiology/American Heart Association published criteria for the
      exclusion of unsuitable cECG curves from ST-segment interpretation. These
      criteria consider medication and 12-lead ECG findings (medication- and 12-lead
      ECG-based criteria) and cECG lead characteristics (cECG-based criteria). METHODS:
      We recorded cECG in 300 patients undergoing major noncardiac surgery. We
      determined postoperative troponin and 12-month outcome. We compared the
      associations of cECG-detected ischemia with troponin and 12-month outcome with
      and without adherence to the criteria. RESULTS: Adherence to the medication- and
      12-lead ECG-based criteria enhanced the association between troponin and
      perioperative ischemia in CM5 (odds ratio, 3.74; 95% confidence interval, 1.88
      7.44) and 7.03 (2.67-18.49), respectively; P = .049). Similarly, the association
      between ischemia in CM5 and 12-month outcome tended to increase (P = .081).
      CONCLUSIONS: Applying the guideline criteria for the interpretation of cECG
      enhanced cECG diagnostic value in surgical patients.

PMID- 19595363
TI  - Insulin pump therapy for type 1 diabetes treatment in a girl with Down's
      syndrome.
AB  - We present the case of a 29.5-year-old girl with Down's syndrome, type 1 diabetes
      mellitus (DMT1), autoimmune thyroiditis and celiac disease starting on insulin
      pump therapy. After 22-month follow-up hemoglobin A1c dropped from 9% to 6.8%,
      even with a lower insulin requirement and no change in BMI.

PMID- 19595364
TI  - Early life origins of low-grade inflammation and atherosclerosis risk in children
      and adolescents.
AB  - OBJECTIVE: To examine the relationship between birth weight and later low-grade
      inflammation in children and adolescents. STUDY DESIGN: We selected 166 children
      (49.4% boys; aged, 9.5 +/- 0.3 years) and 126 adolescents (43.7% males; aged,
      15.5 +/- 0.4 years) from the Swedish part of the European Youth Heart Study.
      Birth weight data were collected from parental recall. Low-grade inflammatory
      markers include C-reactive protein, fibrinogen, and complement factors C3 and C4.
      Fatness was measured by the sum of 5 skinfold thicknesses. Cardiorespiratory
      fitness was measured with a maximal ergometer bike test. The association between
      birth weight and low-grade inflammatory markers was examined with multiple
      regression analyses. RESULTS: Birth weight was negatively associated with
      fibrinogen (beta = -0.059; P = .036), C3 (beta = -0.019; P = .010), and C4 (beta
      = -0.024; P = .031), after controlling for sex, pubertal status, mother's body
      mass index and socioeconomic status, fatness and fitness. Birth weight was not
      associated to later C-reactive protein level (all P > .1). CONCLUSIONS: Our
      results showed that smaller birth weight is associated with chronic low-grade
      inflammation in children and adolescents. Because of the implication of
      complement factors on atherosclerosis process, these results contribute to
      explain the increased cardiovascular risk associated with low birth weight.

PMID- 19595365
TI  - Atherosclerosis in survivors of Kawasaki disease.
AB  - OBJECTIVES: To test the hypothesis that long-term survivors of low-risk Kawasaki
      disease (KD) have ongoing vascular inflammation and dysfunction and a higher risk
      of accelerated atherosclerosis than healthy control subjects. STUDY DESIGN:
      Twenty-eight patients with KD (7-20 years after acute illness) and 27 age-matched
      healthy control subjects were examined for medical and dietary history, serum
      markers of atherosclerotic risk and inflammation, carotid intimal-medial
      thickness (CIMT) with vascular ultrasound scanning and arterial stiffness with
      applanation tonometry. RESULTS: Patients and control subjects were similar in
      age, sex, body mass index, waist-to-hip ratio, blood pressure, cigarette smoking,
      family history, diet, high-density lipoprotein cholesterol level, lipoprotein (a)
      level, homocysteine level, glucose level, insulin level, CIMT, arterial
      stiffness, C-reactive protein level, and inflammatory cytokine level. Levels of
      total cholesterol and apolipoprotein B were significantly higher in patients with
      KD than in control subjects. CONCLUSIONS: There was no evidence of increased
      atherosclerosis. Small but significant differences in cholesterol and
      apolipoprotein B levels could suggest increased future risk for atherosclerosis
      and warrant further study.

PMID- 19595366
TI  - DiGeorge anomaly in the absence of chromosome 22q11.2 deletion.
AB  - OBJECTIVE: To test the hypothesis that the prevalence of deletion 22q11.2 among
      individuals who meet criteria for DiGeorge anomaly (DGA) is lower than the 90%
      commonly cited. STUDY DESIGN: Participants were identified through retrospective
      chart reviews on all patients who underwent testing for deletion 22q11.2 and all
      patients with a diagnosis of "DiGeorge" or any of the major criteria associated
      with DGA at a large pediatric hospital over a period of 6 years. DGA was
      confirmed in 64 individuals, based on the presence of at least 2 of the following
      features: (1) cellular immune deficiency and/or absence of part or all of the
      thymus; (2) hypocalcemia and/or parathyroid deficiency; (3) congenital heart
      disease. RESULTS: Of the 64 individuals with DGA, 29 (45%) did not have a
      chromosome 22q11.2 deletion. Among this deletion-negative subset, diabetic
      embryopathy and other chromosome abnormalities were the most commonly recognized
      underlying etiologies. CONCLUSIONS: These findings challenge a widely held belief
      that nearly 90% of DGA is due to chromosome 22q11.2 deletion. This study also
      calls attention to the heterogeneity of DGA, highlights similarities and
      differences between those with and without a chromosome 22q11.2 deletion, and
      attempts to resolve some confusing features of conditions associated with DGA.

PMID- 19595367
TI  - Randomized trial of a parenting intervention for very preterm infants: outcome at
      2 years.
AB  - OBJECTIVES: To determine the efficacy of a neonatal parenting intervention for
      improving development in very preterm infants. STUDY DESIGN: A cluster
      randomized, controlled trial with a cross-over design and washout period was
      conducted in 6 neonatal centers. Two hundred thirty-three babies <32 weeks'
      gestation were recruited (intervention = 112; control = 121). Intervention
      families received weekly Parent Baby Interaction Programme (PBIP) sessions during
      neonatal intensive care unit admission and up to 6 weeks after discharge. Control
      families received standard care. All 195 infants remaining in the study at 24
      months' corrected age were assessed by psychologists blinded to group allocation.
      RESULTS: There was no significant difference in Mental Development Index (-0.9
      points; 95% CI, -5.0, 3.2) or Psychomotor Development Index (2.5; -3.3, 8.4)
      scores between the intervention and control groups and no significant effect of
      intervention on Mental Development Index or Psychomotor Development Index scores
      for subgroups dichotomized by gestational age (<28 weeks/> or =28 weeks), parity
      (1st/other child) or mother's cohabiting status (supported/unsupported).
      CONCLUSIONS: There was no effect of PBIP on infant development at 2 years'
      corrected age. Parenting interventions may be better delivered after discharge or
      targeted for preterm infants with high biological and social risk.

PMID- 19595368
TI  - Increased detection rate of Kawasaki disease using new diagnostic algorithm,
      including early use of echocardiography.
AB  - OBJECTIVE: To determine the incidence of Kawasaki disease (KD) in Northern France
      by using new American Heart Association (AHA) criteria. STUDY DESIGN: A 1-year
      prospective multicenter cohort study was performed in all pediatric departments.
      Patients <18 years old, who were admitted for prolonged but initially unexplained
      fever or suspected KD were included. All patients received the standard treatment
      considered appropriate by their physicians. A descriptive analysis and comparison
      of patients with complete and incomplete forms of KD were performed. The
      incidence of confirmed cases of KD (complete and incomplete forms) was
      calculated. RESULTS: Seventy-seven children were included (39 in whom KD was
      diagnosed). Of the patients with KD, 26 (67%) met the classic AHA case
      definition, and 7 (18%) had incomplete KD. Cardiac ultrasound scanning was
      helpful in the diagnosis of 6 of 7 patients with incomplete KD (86%). The final
      incidence of confirmed KD was 9 of 100,000 children <5 years of age. In 6
      children (15%) the diagnosis of KD was uncertain, but they were successfully
      treated for it. Coronary disease was identified in 48% of patients with confirmed
      KD. CONCLUSION: The incidence of KD is higher than previously reported, in part
      because earlier reports did not include incomplete forms. New AHA criteria
      (laboratory tests and early echocardiography) were helpful for the diagnosis of
      incomplete forms of KD.

PMID- 19595369
TI  - Bed-sharing at 3 months and breast-feeding at 1 year in southern Brazil.
AB  - OBJECTIVE: To investigate the association between bedsharing at age 3 months and
      breastfeeding (BF) at age 12 months. STUDY DESIGN: Almost all children born in
      Pelotas, Brazil in 2004 (99.2%) were enrolled in a cohort study. At birth, age 3
      months, and age 12 months, mothers were interviewed to gather information on
      sociodemographic, reproductive, BF, and bedsharing characteristics. Bedsharing
      was defined as habitual sharing of a bed between mother and child for the entire
      night or part of the night. The analysis was limited to children from single
      births who were breastfed at 3 months. Multivariate analyses were carried out
      using Poisson regression. RESULTS: Of 4231 live births, 2889 were breastfed at
      age 3 months. The prevalence of BF at age 12 months was 59.2% in the children who
      bedshared at 3 months and 44% in those who did not (adjusted prevalence ratio
      [PR] for weaning= 0.75; 95% confidence interval [CI] = 0.69-0.81; P < .001).
      Among children who were exclusively breastfed at 3 months, 75.1% of those who
      also bedshared were still breastfed at age 12 months, versus 52.3% of those who
      did not bedshare (adjusted PR = 0.63; 95% CI = 0.53- 0.75; P < .001). The
      adjusted PR was 0.74 (95% CI = 0.60-0.90; P = .003) in children who were
      predominantly breastfed and 0.83 (95% CI = 0.76-0.90; P < .001) in those who were
      partially breastfed. CONCLUSIONS: Bedsharing at 3 months protected against
      weaning up to age 12 months.

PMID- 19595370
TI  - Pediatric biobanks: approaching informed consent for continuing research after
      children grow up.
AB  - OBJECTIVE: Proposals for pediatric biobanks have prompted questions of whether
      parental permission is sufficient to continue to use biological samples and data
      after the children become adults. The objective of this study was to examine
      adults' attitudes about continued research with their pediatric samples/data,
      particularly when they could not be located to provide consent. STUDY DESIGN:
      Telephone interviews were conducted with 1186 patients from 5 academic medical
      centers by using a hypothetical scenario. RESULTS: Most respondents, 799 (67%),
      would not be concerned about the use of their sample/data after they reached
      adulthood. Those respondents who were concerned were more likely to be more
      private about their medical records, less trusting of medical researchers, or
      African-American. A total of 543 respondents (46%) believed their consent should
      be obtained to continue using their sample/data for research. Of these, 407
      respondents (75%) would be at least moderately willing to give consent, when
      asked. Of the 1186 respondents, 310 (26%) would not want researchers to use their
      sample/data when they could not be located to ask for consent. CONCLUSION: The
      data are consistent with the normative view that when feasible, adults should be
      asked for consent for continued research on their data collected during
      childhood, but it is generally acceptable to continue to conduct research when
      adults cannot be located. Further public engagement may help determine how best
      to balance the potential social value of continued research using pediatric
      samples/data and the expectations for explicit consent expressed by a minority of
      respondents that may reflect concerns about privacy and trust.

PMID- 19595372
TI  - Intentional exposure to loud music: the second MTV.com survey reveals an
      opportunity to educate.
AB  - OBJECTIVES: Music-induced hearing loss (MIHL), an unconsciously self-inflicted
      public health concern, could evolve into an epidemic because of the appeal of
      loud music. After media attention about a previous hearing-loss survey with Music
      Television (MTV.com), we hypothesized that a repeat survey could compare
      awareness and behavior trends. STUDY DESIGN: We incorporated the 2002 survey into
      the new 73-question instrument presented to random visitors on the MTV.com
      website in 2007. A P < .05 value was used for independent t and z- tests.
      RESULTS: A total of 2500 completed surveys were analyzed. Hearing loss was
      considered a problem by 32% of respondents compared with other health issues such
      as drug/alcohol use (62%). However, nearly half of the respondents admitted
      experiencing symptoms such as tinnitus or hearing loss after loud music exposure.
      Health care providers were the least likely source of MIHL awareness despite the
      respondents favoring provider education for hearing protection behavior
      modification. CONCLUSION: Most respondents still could not recall learning about
      prevention of potential hearing loss, although the media has become the most
      informative source. Most respondents indicated that they would adopt protective
      ear behavior if made aware of hearing loss risk, especially if informed by health
      care professionals, revealing an educational opportunity.

PMID- 19595371
TI  - Higher infant blood lead levels with longer duration of breastfeeding.
AB  - OBJECTIVE: To determine whether longer breastfeeding is associated with higher
      infant lead concentrations. STUDY DESIGN: Data were analyzed from 3 studies of
      developmental effects of iron deficiency in infancy: Costa Rica (1981-1984),
      Chile (1991-1996), and Detroit (2002-2003). The relation between duration of
      breastfeeding and lead levels was assessed with Pearson product-moment or partial
      correlation coefficients. RESULTS: More than 93% of the Costa Rica and Chile
      samples was breastfed (179 and 323 breastfed infants, respectively; mean weaning
      age, 8-10 months), as was 35.6% of the Detroit sample (53 breastfed infants; mean
      weaning age, 4.5 months). Lead concentrations averaged 10.8 microg/dL (Costa
      Rica, 12-23 months), 7.8 microg/dL (Chile, 12 months), and 2.5 microg/dL
      (Detroit, 9-10 months). Duration of breastfeeding as sole milk source and total
      breastfeeding correlated with lead concentration in all samples (r values = 0.14
      0.57; P values = .06-<.0001). CONCLUSIONS: Longer breastfeeding was associated
      with higher infant lead concentration in 3 countries, in 3 different decades, in
      settings differing in breastfeeding patterns, environmental lead sources, and
      infant lead levels. The results suggest that monitoring lead concentrations in
      breastfed infants be considered.

PMID- 19595373
TI  - Low inhibitory control and restrictive feeding practices predict weight outcomes.
AB  - OBJECTIVE: A priority for research is to identify individuals early in
      development who are particularly susceptible to weight gain in the current,
      obesogenic environment. This longitudinal study investigated whether early
      individual differences in inhibitory control, an aspect of temperament, predicted
      weight outcomes and whether parents' restrictive feeding practices moderated this
      relation. STUDY DESIGN: Participants included 197 non-Hispanic white girls and
      their parents; families were assessed when girls were 5, 7, 9, 11, 13, and 15
      years old. Measures included mothers' reports of girls' inhibitory control
      levels, girls' reports of parental restriction in feeding, girls' body mass
      indexes (BMIs), and parents' BMIs, education, and income. RESULTS: Girls with
      lower inhibitory control at age 7 had higher concurrent BMIs, greater weight
      gain, higher BMIs at all subsequent time points, and were 1.95 times more likely
      to be overweight at age 15. Girls who perceived higher parental restriction
      exhibited the strongest inverse relation between inhibitory control and weight
      status. CONCLUSION: Variability in inhibitory control could help identify
      individuals who are predisposed to obesity risk; the current findings also
      highlight the importance of parenting practices as potentially modifiable factors
      that exacerbate or attenuate this risk.

PMID- 19595374
TI  - Impaired vascular function in obese adolescents with insulin resistance.
AB  - OBJECTIVE: To evaluate endothelial function (EF) in a cohort of obese adolescents
      with impaired insulin sensitivity. STUDY DESIGN: Cardiovascular risk factors and
      adipocytokines, along with digital hyperemia, were evaluated by peripheral
      arterial tonometry (PAT) in adolescents with obesity and insulin resistance (IR)
      in relation to healthy, nonobese controls. RESULTS: The obese and control
      subjects were of similar age (13.4+/-1.7 years vs 14.0+/-1.4 years) and sex. The
      obese subjects had IR (mean homeostasis model of assessment [HOMA] score=5.4; 95%
      confidence interval=3.3-7.5) and significantly greater body mass index (BMI) (BMI
      z-score 2.4+/-0.2 kg/m(2) vs 0.0+/-0.8 kg/m(2)) and waist circumference (WC)
      measures (109.6+/-11.1cm vs 70.5+/-9.4 cm) with elevated low-density lipoprotein
      cholesterol (LDL-C), triglyceride, and high-sensitivity C-reactive protein
      levels. The mean PAT ratio was significantly lower in obese adolescents compared
      with controls (1.51+/-0.4 vs 2.06+/-0.4; P=.002), indicative of impaired EF.
      Linear regression demonstrated associations between PAT ratio and BMI, WC, age,
      and LDL-C but not between PAT and leptin, resistin, or adiponectin levels or IR.
      CONCLUSIONS: Obese adolescents with IR exhibited significantly worse EF as
      assessed by PAT compared with healthy, nonobese controls, and EF showed a
      significant association with measures of adiposity and other cardiovascular risk
      factors.

PMID- 19595375
TI  - Automated adjustment of inspired oxygen in preterm infants with frequent
      fluctuations in oxygenation: a pilot clinical trial.
AB  - OBJECTIVE: To assess the efficacy of a system for automated fraction of inspired
      oxygen (FiO(2)) adjustment in maintaining oxygen saturation (SpO(2)) within an
      intended range in preterm infants with spontaneous fluctuations in SpO(2). STUDY
      DESIGN: Sixteen infants (gestational age, 24.9 +/- 1.4 weeks; birth weight, 678
      +/- 144 g; age, 33 +/- 15 days) with frequent hypoxemia episodes underwent two 4
      hour periods of FiO(2) adjustment by clinical personnel (routine) and the
      automated system (automated). RESULTS: Compared with the routine period, the
      percent time within intended SpO(2) range (88%-95%) increased during the
      automated period (58% +/- 10% versus 42% +/- 9%; P < .001), whereas the percent
      time with SpO(2) higher than the intended range and >or=98% were reduced (9% +/-
      10% versus 31% +/- 8% [P < .001] and 3% +/- 5% versus 16% +/- 9% [P < .001],
      respectively). Percent time with SpO(2) < 88% increased during the automated
      period (33% +/- 7% versus 27% +/- 9%; P = .003) because of more frequent
      episodes, whereas the time with SpO(2) < 75% did not differ. The 4-hour median
      FiO(2) was lower during the automated period (29% +/- 4% versus 34% +/- 5%; P <
      .001). CONCLUSION: Automated FiO(2) adjustment improved maintenance of SpO(2)
      within the intended range and reduced hyperoxemia and FiO(2). These findings
      should be examined in longer periods with standard clinical conditions and,
      eventually, in the context of randomized trials powered to detect clinically
      important effects on outcome.

PMID- 19595376
TI  - Decreased chloride levels of cerebrospinal fluid in patients with amyotrophic
      lateral sclerosis.
AB  - Recent studies have suggested that the elevation of intracellular chloride
      contributes to excitotoxic cell death in motor neuron and can be related to the
      pathogenesis of amyotrophic lateral sclerosis (ALS). We investigated whether
      chloride levels in cerebrospinal fluid (CSF) and serum were lower in ALS patients
      than in control patients with other neurological diseases (OND). We also examined
      the relationship between chloride levels and clinical ALS phenotypes. We measured
      chloride levels (CSF and serum) in 27 ALS patients and 33 age- and gender-matched
      OND controls admitted to our hospital for diagnosis. The CSF chloride levels were
      lower in ALS patients (117 [range 102-130] mmol/L) than in OND controls (126
      [range 114-134] mmol/L) (P<0.0001). However, no significant difference was found
      in their serum chloride levels (P>0.05). There was no significant difference in
      CSF chloride levels among the sub-groups of ALS patients classified according to
      their age, gender, duration of illness, clinical state and type of onset
      (P>0.05). CSF chloride levels already significantly decreased in ALS patients at
      the time of diagnosis. We conclude that the elevation of intracellular chloride
      would cause the reduction of chloride in CSF and be related to the pathogenesis
      of ALS.

PMID- 19595377
TI  - Development of guidelines for ammonia in estuarine and marine water systems.
AB  - The water quality guideline trigger value for ammonia in estuarine and marine
      waters has been revised with the addition of 38 new results to the data set of 21
      used in earlier guideline derivations. Using species sensitivity distributions, a
      new trigger value of 460 microg total NH(3)-N/L was derived for slightly to
      moderately disturbed systems (95% protection concentration, PC95), with a value
      of 160 microg total NH(3)-N/L applying to waters of high conservation value
      (PC99). For sediment pore waters, a guideline trigger value of 3.9 mg total NH(3)
      N/L, derived from the 80th percentile of background data from Sydney Harbour, is
      recommended. This value is likely to be exceeded in degraded sediments subject to
      dredging; however, ocean disposal of such sediments results in rapid decreases in
      porewater ammonia and a guideline trigger value for dissolved ammonia during
      disposal of dredged sediments of 1550 microg total NH(3)-N/L is proposed.

PMID- 19595378
TI  - [Appropriate strategies for the cardiovascular "disease". High-risk patients].

PMID- 19595379
TI  - [Imaging techniques in the diagnosis of neuroendocrine tumors].
AB  - Diagnostic work-up of neuroendocrine tumors (NET) includes clinical assessment,
      biochemical testing and imaging procedures. Endoscopic investigations are
      indicated for identification of NET in the gastrointestinal tract and the
      bronchopulmonary tree. Transabdominal ultrasound has a relatively low sensitivity
      in small lesions, but intraoperative ultrasound improves intraoperative detection
      of lesions. Endoscopic ultrasonography has a high sensitivity to detect tumors in
      pancreatic head and duodenal wall. Radiological procedures, including computed
      tomography (CT) and magnetic resonance imaging (MRI), are well established
      techniques for the investigation of primary tumors, metastatic lesions,
      associated malignancies and follow-up after surgical or medical treatments.
      Somatostatin receptor scintigraphy (SRS) is based on the presence of somatostatin
      receptors in a great proportion of NET. PET is a functional imaging technique
      that reflects tumor metabolism. A multimodality approach, including CT, MRI, SRS,
      ultrasound and endoscopy, is nowadays recommended for detecting these tumors.

PMID- 19595380
TI  - [Low mortality rate in an outbreak of Legionnaires' disease: correlation with the
      cytopathogenity study].
AB  - BACKGROUND: In 2001 an outbreak of Legionnaires' diseases occurred in Murcia,
      Spain, with one of the lowest known rates of associated mortality. We describe
      the clinical data of a subgroup of patients, and present the results from
      molecular and virulence studies to correlate the lower mortality of the overall
      series with the strain virulence. PATIENTS AND METHODS: A subgroup of 86 patients
      from the outbreak of Legionnaires'disease was prospectively included.
      Demographic, risk factors and clinical evolution data were obtained. Moreover, we
      performed a pulsed field gel electrophoresis and cytopathogenicity assay of the
      Murcia outbreak that were compared with other unrelated Legionella isolates.
      RESULTS: Sixty-nine (77.9%) patients were males. The mean age of the patients was
      58.2 years (range: 32-87). Smoking was the most frequent risk factor in 62
      patients (71.7%) and 61 patients (70.2%) had underlying diseases. Clinical,
      laboratory and radiological manifestations were compatible with the atypical
      pneumonia syndrome. The mortality rate was 3.2%. All the clinical L. pneumophila
      isolates analyzed by PFGE showed the same subtype. When analyzing theses strains
      together with other Legionella strains, they were included in the group with
      lower virulence in the cytopathogenicity study. CONCLUSIONS: The most outstanding
      data in this subgroup of patients were: male-sex, smoking, atypical clinical
      manifestations and low mortality. The low virulence of this molecular genotype of
      L. pneumophila may be responsible, in part, for the low mortality observed in the
      outbreak in Murcia.

PMID- 19595381
TI  - Age-related differences in inflammatory markers in men: contribution of visceral
      adiposity.
AB  - As visceral adipose tissue (AT) accumulation and inflammatory markers are known
      to increase with age, we examined whether this age-related change in regional AT
      distribution could contribute to the increase in the concentration of some
      inflammatory markers found with age. Two hundred eight healthy men aged 18.6 to
      72.2 years and covering a wide range of adiposity values (body mass index, 18.5
      39.3 kg/m(2)) were studied. Plasma C-reactive protein (CRP), interleukin-6 (IL
      6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme
      linked immunosorbent assay. Anthropometric characteristics such as height,
      weight, and waist girth were measured; and body mass index was calculated. Cross
      sectional areas of abdominal AT were obtained at L4-L5 by computed tomography.
      Fasting blood samples were collected to determine a complete lipoprotein lipid
      profile, and a 75-g oral glucose tolerance test was performed. Overall, visceral
      AT accumulation was positively correlated with age (r = 0.51, P < .0001) as well
      as with plasma CRP (r = 0.39, P < .0001), IL-6 (r = 0.32, P < .0001), and TNF
      alpha (r = 0.14, P < .05) levels. A significant positive relationship was also
      observed between age and CRP (r = 0.36, P < .0001), IL-6 (r = 0.39, P < .0001),
      or TNF-alpha (r = 0.15, P < .05) concentrations. As middle-aged men were
      characterized by higher CRP (1.32 [25th percentile, 0.71; 75th percentile, 2.71]
      vs 0.66 [0.36, 1.62] mg/L, P < .0001) and IL-6 (1.60 [1.09, 2.28] vs 1.12 [0.77,
      1.60] pg/mL, P < .0001) levels as well as by a greater amount of visceral AT (P <
      .0001) than young men, we have individually matched 43 young men (age, 28.6 +/-
      5.82 years) with 43 middle-aged men (age, 57.6 +/- 5.15 years) on the basis of
      their visceral AT. Matching for visceral AT eliminated the difference between
      middle-aged men and younger adult men in inflammatory markers. These results
      suggest that the age-related variation in CRP and IL-6 is largely explained by
      differences in visceral AT.

PMID- 19595382
TI  - Serum levels of interleukin-18 are reduced by diet and n-3 fatty acid
      intervention in elderly high-risk men.
AB  - Inflammation plays a central role in the development and progression of
      atherosclerosis, and inflammatory markers have been reported to predict
      cardiovascular events. Mediterranean-like diet and very long chain omega-3
      polyunsaturated fatty acid (n-3 PUFA) supplementation have been reported to
      reduce the risk of cardiovascular mortality and morbidity, but the mechanisms are
      not fully clarified. The aims of the present study were to investigate the effect
      of such interventions on serum levels of inflammatory markers, and potential
      associations with changes in serum fatty acids and anthropometric measures. This
      was a randomized 2 x 2 factorial-designed trial comparing the effect of 3 years
      of dietary counseling, n-3 PUFA supplementation (2.4 g/d), or both on different
      measures of atherosclerosis in elderly high-risk men (N = 563). Levels of
      interleukin-18 (IL-18) were decreased by diet (-10.5% vs baseline, P = .012
      compared with no diet) and by n-3 PUFA supplementation (-9.9% vs baseline, P =
      .008 compared with placebo). Other measured inflammatory markers were not
      affected. Changes in IL-18 were significantly correlated to changes in
      triglycerides (r = 0.20, P < .001), eicosapentaenoic acid (r = -0.14, P = .030),
      docosahexaenoic acid (r = -0.14, P = .034), body mass index (r = 0.16, P < .001),
      and waist circumference (r = 0.12, P = .007). In conclusion, levels of IL-18 were
      significantly reduced by Mediterranean-like diet and n-3 PUFA supplementation.
      However, the changes correlated only weakly to changes in triglycerides, serum
      fatty acids, and anthropometric measures. The cardioprotective effects of both
      interventions might thus in part be explained by reduced levels of IL-18, but
      probably beyond changes in serum fatty acids and body composition.

PMID- 19595383
TI  - Effect of adipose tissue on the sexual dimorphism in metabolic flexibility.
AB  - Metabolic flexibility is the ability to transition between fat oxidation (fasting
      state) and glucose oxidation (fed state). We hypothesized that adipose tissue
      inflammation and lipid metabolism contribute to sexual dimorphism in metabolic
      flexibility. Respiratory quotient (DeltaRQ, metabolic flexibility) and
      nonesterified fatty acids (NEFAs) before and during euglycemic-hyperinsulinemic
      clamp were measured in healthy young women (n = 22) and men (n = 56). Adiponectin
      levels were measured in plasma. Abdominal subcutaneous adipose tissue gene
      expression was measured by quantitative reverse transcriptase polymerase chain
      reaction. As compared with men, women had higher DeltaRQ (0.14 +/- 0.04 vs 0.09
      +/- 0.04, P < .01). Fasting RQ and fat cell size were not different between
      sexes. As compared with men, women had lower insulin-suppressed NEFAs (P < .05);
      greater adiponectin levels; and higher expression of adipogenesis, fatty acid
      storage, and oxidation genes (PPARgamma2, PCK1, SCD1, and PPARalpha; P < .05).
      There were no sex differences in messenger RNA of macrophage markers or
      chemokines. Stepwise regression analysis revealed that the only adipose tissue
      characteristics that influenced metabolic flexibility in women were SCD1 and PCK1
      messenger RNA (model R(2) = 0.49, P < .05); in men, these were serum adiponectin
      and insulin-suppressed NEFAs (model R(2) = 0.34, P < .05). Healthy young women
      are more metabolically flexible than men, driven by an increase in insulin
      stimulated glucose oxidation rather than differences in fasting fat oxidation.
      Women have greater capacity for insulin suppression of NEFAs despite similar
      chemokine and macrophage content in adipose tissue. Combined, these results
      provide evidence for a role of adipose tissue characteristics in the sexual
      dimorphism of metabolic flexibility.

PMID- 19595384
TI  - Fish-induced keriorrhea.
AB  - Many deep-sea fishes store large amounts of wax esters in their body for buoyancy
      control. Some of them are frequently caught as by-catch of tuna and other fishes.
      The most noteworthy ones include escolar and oilfish. The accumulation of the
      indigestible wax esters in the rectum through consumption of these fish engenders
      discharges or leakage per rectum as orange or brownish green oil, but without
      noticeable loss of water. This physiological response is called keriorrhea, which
      is variously described as "oily diarrhea," "oily orange diarrhea," or "orange
      oily leakage" by the mass media and bloggers on the internet. Outbreaks of
      keriorrhea have been repeatedly reported across continents. Additional symptoms
      including nausea, vomiting, abdominal cramps, and diarrhea were complained by the
      victims. They are probably due to anxiety or panic when suffering from
      keriorrhea. Escolar and oilfish are banned from import and sale in Italy, Japan,
      and South Korea. Rapid detection of the two fishes is imperative to ensure proper
      labeling and safeguarding of the public before and after any keriorrhea outbreak.

PMID- 19595385
TI  - Haze in beverages.
AB  - Beverages such as beer, wine, clear fruit juices, teas, and formulated products
      with similar ingredients are generally expected by consumers to be clear (free of
      turbidity) and to remain so during the normal shelf life of the product. Hazy
      products are often regarded as defective and perhaps even potentially harmful.
      Since consumers are usually more certain of what they perceive visually than of
      what they taste or smell, the development of haze in a clear product can reduce
      the likelihood of repeat purchasing of a product and can have serious economic
      consequences to a producer. Hazes are caused by suspended insoluble particles of
      colloidal or larger size that can be perceived visually or by instruments. Hazes
      in clear beverages can arise from a number of causes, but are most often due to
      protein-polyphenol interaction. The nature of protein-polyphenol interaction and
      its effect on haze particles, analysis of haze constituents, and stabilization of
      beverages against haze formation are reviewed.

PMID- 19595386
TI  - Carnosine and its possible roles in nutrition and health.
AB  - The dipeptide carnosine has been observed to exert antiaging activity at cellular
      and whole animal levels. This review discusses the possible mechanisms by which
      carnosine may exert antiaging action and considers whether the dipeptide could be
      beneficial to humans. Carnosine's possible biological activities include
      scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS),
      chelator of zinc and copper ions, and antiglycating and anticross-linking
      activities. Carnosine's ability to react with deleterious aldehydes such as
      malondialdehyde, methylglyoxal, hydroxynonenal, and acetaldehyde may also
      contribute to its protective functions. Physiologically carnosine may help to
      suppress some secondary complications of diabetes, and the deleterious
      consequences of ischemic-reperfusion injury, most likely due to antioxidation and
      carbonyl-scavenging functions. Other, and much more speculative, possible
      functions of carnosine considered include transglutaminase inhibition,
      stimulation of proteolysis mediated via effects on proteasome activity or
      induction of protease and stress-protein gene expression, upregulation of
      corticosteroid synthesis, stimulation of protein repair, and effects on ADP
      ribose metabolism associated with sirtuin and poly-ADP-ribose polymerase (PARP)
      activities. Evidence for carnosine's possible protective action against secondary
      diabetic complications, neurodegeneration, cancer, and other age-related
      pathologies is briefly discussed.

PMID- 19595387
TI  - Recent advances in the microbial safety of fresh fruits and vegetables.
AB  - Foodborne illness outbreaks linked to fresh produce are becoming more frequent
      and widespread. High impact outbreaks, such as that associated with spinach
      contaminated with Escherichia coli O157:H7, resulted in almost 200 cases of
      foodborne illness across North America and >$300 m market losses. Over the last
      decade there has been intensive research into gaining an understanding on the
      interactions of human pathogens with plants and how microbiological safety of
      fresh produce can be improved. The following review will provide an update on the
      food safety issues linked to fresh produce. An overview of recent foodborne
      illness outbreaks linked to fresh produce. The types of human pathogens
      encountered will be described and how they can be transferred from their normal
      animal or human host to fresh produce. The interaction of human pathogens with
      growing plants will be discussed, in addition to novel intervention methods to
      enhance the microbiological safety of fresh produce.

PMID- 19595388
TI  - Understanding oil absorption during deep-fat frying.
AB  - One of the most important quality parameters of fried food is the amount of fat
      absorbed during the process, which undermines recent consumer trends toward
      healthier food and low-fat products. In order to obtain a product with a low fat
      content, it is essential to understand the mechanisms involved during the frying
      process, so that oil migration into the structure can be minimized. To get such
      an understanding, this chapter briefly describes the frying process from
      technological and scientific perspectives. First, it gives a general overview of
      the frying process and describes the most important quality attributes of fried
      food. Thereafter, it centers on key nutritional aspects, particularly on the
      effect of excessive oil consumption on human health, oil degradation, and toxic
      compounds generation in fried food. Finally, this chapter discusses the most
      important factors affecting oil absorption, oil absorption kinetics, and
      different strategies that may be adopted to decrease oil content.

PMID- 19595390
TI  - Global approaches to study gene regulation.

PMID- 19595389
TI  - Introduction of oats in the diet of individuals with celiac disease: a systematic
      review.
AB  - Celiac disease is an immune-mediated disease, triggered in genetically
      susceptible individuals by ingested gluten from wheat, rye, barley, and other
      closely related cereal grains. The only treatment for celiac disease is a strict
      gluten-free diet for life. This paper presents a systematic review of the
      scientific literature on the safety of pure oats for individuals with celiac
      disease, which historically has been subject to debate. Limitations identified
      within the scientific database include: limited data on long-term consumption,
      limited numbers of participants in challenge studies, and limited reporting about
      the reasons for withdrawals from study protocols. Furthermore, some evidence
      suggests that a small number of individuals with celiac disease may be intolerant
      to pure oats and some evidence from in vitro studies suggests that an
      immunological response to oat avenins can occur in the absence of clinical
      manifestations of celiac disease as well as suggesting that oat cultivars vary in
      toxicity. Based on the majority of the evidence provided in the scientific
      database, and despite the limitations, Health Canada and the Canadian Celiac
      Association (CCA) concluded that the majority of people with celiac disease can
      tolerate moderate amounts of pure oats. The incorporation of oats into a gluten
      free diet provides high fiber and vitamin B content, increased palatability, and
      beneficial effects on cardiovascular health. However, it is recommended that
      individuals with celiac disease should have both initial and long-term
      assessments by a health professional when introducing pure oats into a gluten
      free diet.

PMID- 19595391
TI  - Sexual victimization as a risk factor for residential mobility: a case-control
      study using the Danish registry system.
AB  - OBJECTIVES: Increased residential mobility has been proposed as an undesirable
      consequence for the victims of sexual victimization. This study aimed to test the
      hypothesis that serious sexual victimization predicted high levels of residential
      mobility after controlling for previous levels of residential mobility. STUDY
      DESIGN: A case-control design was used. Data were from the Danish civil registry
      system. METHODS: All females who had visited a centre for rape victims over a 1
      year period were identified, and demographic information was collected based on
      the Danish civil registry number. A control group of 20 women for each rape
      victim with the same age and living in the same municipality in the year of the
      rape was also used. RESULTS: The results indicate that attendance at the centre
      for rape victims, higher previous levels of residential mobility and being single
      significantly increase the likelihood of subsequent high residential mobility.
      CONCLUSIONS: Sexual victimization has a unique and significant role in predicting
      residential mobility, above and beyond the influence of previous residential
      mobility.

PMID- 19595392
TI  - [Neonatal renal vein thrombosis: early diagnosis using Doppler ultrasonography
      and long-term sequelae].
AB  - OBJECTIVE: To describe the physiopathological mechanisms in perinatal renal vein
      thrombosis and the associated risk factors, with emphasis on the clinical and
      radiological characteristics and on the long-term evolution. MATERIAL AND
      METHODS: We retrospectively studied a total of 11 cases of neonatal renal vein
      thrombosis; the mean age of patients at diagnosis was 3 days. We analyzed the
      type of presentation, the clinical manifestations, and the findings at B-mode and
      Doppler ultrasonography, as well as the treatment undertaken and the long-term
      sequelae. RESULTS: At the time of diagnosis, the triad of a palpable mass,
      unequivocal hematuria, and thrombocytopenia was present in only 63.63% of
      patients. A prothrombotic risk factor was identified in the newborn or mother in
      45.45% of cases. At ultrasonographic examination, all newborns had enlarged
      kidneys and in all cases it was impossible to differentiate between the renal
      cortex and the renal medulla. In 4 of the 11 cases, hyperechogenic intramedullary
      linear images characteristic of the initial stage of thrombosis were identified.
      Functional follow-up studies using DMSA (dimercaptosuccinic acid) and MAG-3
      (mercaptoacetyltriglycine acid) revealed morphological abnormalities in all
      patients; 7 patients had a nonfunctioning kidney. CONCLUSIONS: Visualizing
      echogenic bands within the medulla should alert radiologists to the initial phase
      of renal vein thrombosis and enable the appropriate treatment to be administered.
      With the exception of cases discovered before birth, renal vein thrombosis has a
      poor prognosis, with atrophy and renal failure in the long term.

PMID- 19595393
TI  - Editorial note.

PMID- 19595395
TI  - In-hospital complications and long-term outcomes of the paclitaxel drug-eluting
      stent in acute ST-elevation myocardial infarction: a real-world experience from a
      high-volume medical center.
AB  - BACKGROUND: The paclitaxel drug-eluting stent (Taxus, Boston Scientific) is FDA
      approved for treatment of coronary artery disease in simple, noncomplex coronary
      lesions. In this registry, we sought to investigate the procedural success and
      long-term outcomes of patients receiving the Taxus stent in the setting of acute
      ST-elevation myocardial infarction (STEMI) in a busy single-center interventional
      program. METHODS: This is a single-center retrospective analysis of prospectively
      collected in-hospital data with postdischarge follow-up achieved by phone calls
      and review of medical records. Data were audited by an independent monitor, and
      outcomes were adjudicated by an experienced interventional cardiologist. All
      patients with STEMI over the period of 2 years (2005 and 2006) with native de
      novo lesions who received the Taxus stent were included. Patients receiving bare
      metal stents were excluded. The primary outcome was the combined end point of
      cardiac death, recurrent nonfatal MI, and target lesion revascularization (TLR)
      on follow-up. RESULTS: Of 198 patients included in this study, follow-up data
      were obtained in 172 (86.9%) patients. The mean age was 63+/-14.9 years. There
      were 59.1% males. Patients had the following cardiac risk factors: diabetes
      20.7%, hypertension 60.6%, hyperlipidemia 87.8%, and current smoking 48%. In
      hospital complications included death 5.1%, acute closure with stent thrombosis
      1%, vascular complications 2.9%, and cardiogenic shock 6.6%. The mean follow-up
      period (days) was 317.3+/-239.3. The primary end point of cardiac death, nonfatal
      MI, and TLR was met in 12.4%. Individual end points on follow-up were cardiac
      death 2.5%, total death 4.9%, TLR 8.1%, target vessel revascularization 19.9%,
      stroke 1.2%, nonfatal MI 5%, and acute stent thrombosis 5.5% (definite 4.3%,
      probable 0.6%, possible 0.6%; Academic Research Consortium definition).
      CONCLUSION: The use of the Taxus stent in acute STEMI is associated with a low
      postdischarge combined end point of cardiac death, nonfatal MI, and TLR and a
      definite/probable 4.9% in-stent thrombosis rate, which is within the reported
      range of data published in "real-world" registry.

PMID- 19595394
TI  - Preprocedural high-sensitivity C-reactive protein predicts death or myocardial
      infarction but not target vessel revascularization or stent thrombosis after
      percutaneous coronary intervention.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) elevation is associated
      with poor clinical outcome in patients with coronary artery disease (CAD).
      However, the prognostic value of preprocedural hs-CRP elevation before coronary
      stent implantation remains debated especially regarding restenosis and target
      vessel revascularization (TVR). Furthermore, whether hs-CRP elevation may predict
      stent thrombosis (ST) is unknown. METHODS: We included 560 consecutive patients,
      who underwent coronary stent implantation in our institution. Blood samples for
      hs-CRP determination were obtained immediately before the procedure. During a
      median follow-up of 12.5 months, cardiovascular events including death,
      myocardial infarction (MI), TVR, and ST were systematically included. RESULTS:
      Median hs-CRP was 3.10 [25-75th percentile: 1.36-8.63] mg/l. There were 27 (4.8%)
      deaths, 17 (3.1%) nonfatal MI, 58 (10.5%) TVR, and 12 (2.1%) ST. The composite
      criteria death-MI occurred in 44 (7.9%) patients. Independent predictors of the
      composite death-MI were hs-CRP level [hazard ratio (HR)=1.33 (95% CI: 1.05-1.70);
      P=.021], diabetes (P=.003), and multivessel CAD (P=.011). The composite death-MI
      occurred in 31 (13.3%) of the 233 patients with hs-CRP >4.63 mg/l vs. 13 (4.0%)
      of the 327 patients with hs-CRP <4.63 mg/L (P<.001). By contrast, hs-CRP
      predicted neither TVR [HR=0.88 (0.73-1.08); P=.23] nor ST [HR=1.15 (0.77-1.71);
      P=.49]. CONCLUSION: High hs-CRP levels before coronary stent implantation are
      associated with risk of death or MI, but are not related to TVR or ST. These data
      suggest that preprocedural hs-CRP is more a predictor of global cardiovascular
      risk than a predictor of stent-related complications.

PMID- 19595396
TI  - Head-to-head comparison of bivalirudin versus heparin without glycoprotein
      IIb/IIIa inhibitors in patients with acute myocardial infarction undergoing
      primary angioplasty.
AB  - BACKGROUND: In patients receiving primary percutaneous coronary intervention for
      ST elevation myocardial infarction (STEMI), bivalirudin with provisional
      glycoprotein (GP) IIb/IIIa inhibitors has been demonstrated to be noninferior to
      heparin plus systematic GP IIb/IIIa inhibitors in preventing recurrent ischemic
      events with improved safety in terms of bleeding. However, no study has been
      performed comparing head-to-head bivalirudin with heparin without GP IIb/IIIa
      inhibitor infusion in STEMI patients. METHODS: We retrospectively studied 899
      consecutive patients who presented with STEMI treated by primary angioplasty
      within 12 h after symptoms. Among them, 566 received bivalirudin and 333 received
      unfractionated heparin. Their in-hospital outcome in terms of efficacy and safety
      was assessed using rates of major adverse cardiac events (MACE) and major
      bleeding, respectively. Clinical, angiographic and procedural characteristics
      were well matched between the two groups. RESULTS: Patients in the heparin group
      more frequently required intra-aortic balloon pumping (6.6% vs. 3.6%, P=.037).
      Regarding the safety end point, the MACE rate, including death, ischemic stroke
      and urgent repeated revascularization, was low and similar in both groups (2.7%
      bivalirudin vs. 1.2% heparin, P=.15). The rate of major bleeding, including major
      hematoma, gastrointestinal bleeding and hematocrit drop >15% during
      hospitalization, was high and identical in the two groups (4.1% bivalirudin vs.
      4.2% heparin, P=.92). CONCLUSION: This study suggests that bivalirudin and
      heparin present similar safety and efficacy profiles when used without GP
      IIb/IIIa inhibitor infusion during primary angioplasty.

PMID- 19595397
TI  - Beta endovascular brachytherapy using CO2-filled centering catheter for treatment
      of recurrent superficial femoropopliteal artery disease.
AB  - BACKGROUND: Recurrent disease (restenosis) after endovascular treatment of the
      superficial femoral artery (SFA) remains a major problem. We evaluated the
      efficacy of beta-endovascular brachytherapy using the CORONA centering catheter
      in patients with SFA restenosis in a single-arm Phase II trial. METHODS AND
      RESULTS: A total of 28 patients (mean age 70 years; 16 female, 12 male) with
      recurrent SFA stenosis were treated, and in-stent restenosis was present in 17
      patients (61%). Brachytherapy was performed with strontium-90 beta source using a
      7-French CO(2)-filled one-segment centering catheter. New stents had to be
      applied in two cases. Mean interventional length was 129 mm (range 20-240 mm). A
      dose of 14 Gy in vessel radius (postinterventional) plus 2 mm was applied in 24
      patients and 18.4 Gy in four patients. Treatment time was 7 min 32 s per
      radiation segment. No major adverse events occurred. Patients were followed by
      ankle-brachial index and duplex sonography for a median of 42 months. Cumulative
      restenosis rates at 1, 2, and 3 years were 9%, 28%, and 40%, respectively. Target
      vessel revascularization was performed in seven cases (25%). CONCLUSIONS: In
      comparison to literature data, the treatment of SFA restenosis with beta
      brachytherapy may improve long-term patency.

PMID- 19595398
TI  - Drug-eluting stent fracture and acute coronary syndrome.
AB  - BACKGROUND: Coronary stent fracture is an underrecognized entity but has been
      reported more frequently in the drug-eluting stent (DES) era. Nevertheless, the
      clinical implications of coronary stent fracture remain unclear. METHODS AND
      MATERIALS: A literature search for reports of DES fracture was conducted via
      MEDLINE, and the US Food and Drug Administration Manufacturer and User facility
      Device Experience (MAUDE) database was accessed via the internet and interrogated
      for reports of stent fracture between January 1, 2003, and April 30, 2008. Each
      report was reviewed, and clinical information was extracted for analysis.
      RESULTS: The MEDLINE search identified 202 cases of coronary DES fracture, with
      95% of cases involving Cypher sirolimus-eluting stents. Clinical information
      regarding patient presentation was available in 96 cases. Patients presented with
      ST-elevation myocardial infarction (STEMI) or stent thrombosis in six cases (6%)
      and with unstable angina or non-STEMI (NSTEMI) in 40 cases (42%). The MAUDE
      database search identified 337 stent fracture reports, with 97% of cases
      involving Cypher stents. Clinical information regarding patient presentation was
      available 193 cases. Patients presented with STEMI or stent thrombosis in 24
      cases (12%) and with unstable angina or NSTEMI in 36 cases (19%). CONCLUSIONS:
      Most reports of drug-eluting stent fracture involve Cypher stents. DES fracture
      can be associated with stent thrombosis, myocardial infarction and angina.
      However, whether the incidence of such events reported in the literature and in
      the MAUDE database is representative of all patients experiencing stent fracture
      remains unclear.

PMID- 19595400
TI  - Left circumflex coronary artery to hepatic vein fistula: a case report and brief
      review of coronary vasculogenesis.
AB  - Coronary artery fistulas are rare coronary artery anomalies. Their clinical
      significance varies from a long asymptomatic course to overt heart failure and
      death. They are often detected incidentally with diagnostic coronary angiograms.
      Cardiologists increasingly encounter coronary artery fistulas secondary to recent
      improvements in cardiovascular imaging modalities. Management is still
      controversial, especially in asymptomatic cases with less significant shunts.
      Here, we describe a 62-year-old woman with a left circumflex artery to hepatic
      vein fistula found on coronary angiography. The patient is being managed
      conservatively using nuclear imaging studies and echocardiographic evaluation.

PMID- 19595399
TI  - Golden jubilee of hypertrophic cardiomyopathy: is alcohol septal ablation the
      gold standard?
AB  - In the golden jubilee year of the first recognition of hypertrophic obstructive
      cardiomyopathy, we are discussing the intricacies and impact of alcohol septal
      ablation (ASA) in the treatment of this clinical entity. Since its first
      revelation 14 years ago, ASA has become a well-established treatment modality for
      symptomatic hypertrophic obstructive cardiomyopathy patients. With better
      recognition of the implication of first septal branch and right dose of alcohol
      to be used for ablation, the incidence of complications like complete heart block
      are coming down along with better procedural success rates. In appropriately
      selected patients and in expert hands ASA has produced excellent results.
      Surgical myectomy, even though it has produced excellent results, is available
      only at a few centers and patient preference is tilted more for a less invasive
      procedure like ASA. This has contributed towards far more ASAs being performed
      worldwide than surgical myectomies. While more than 5000 ASAs have been performed
      in the last 14 years, the number of patients who have had myectomy remains around
      3000-4000. The pendulum of gold standard may have started swinging away from
      surgical myectomy towards ASA.

PMID- 19595401
TI  - Use of the Proxis embolic protection device for guide anchoring and stent
      delivery during complex saphenous vein graft interventions.
AB  - Optimal guide catheter engagement and an embolic protection strategy are crucial
      for successful saphenous vein graft (SVG) percutaneous coronary interventions. We
      describe three SVG cases during which the use of Proxis device not only provided
      embolic protection, but also served as a guide catheter anchor allowing distal
      stent delivery, after failed attempts using conventional techniques.

PMID- 19595402
TI  - Simultaneous late stent thrombosis in two coronary arteries following drug
      eluting stent implantation.
AB  - Late stent thrombosis has emerged as an infrequent but serious complication of
      drug-eluting stent (DES) implantation. Premature cessation of dual antiplatelet
      therapy is the most common risk factor for its occurrence. In the era of
      multivessel stenting with DES, there is a potential for multivessel late stent
      thrombosis following cessation of dual antiplatelet therapy. We present a rare
      case of a patient who sustained simultaneous late stent thromboses in DESs
      implanted in two coronary arteries as a result of premature cessation of dual
      antiplatelet therapy.

PMID- 19595403
TI  - ST-Segment elevation acute myocardial infarction due to severe hypotension and
      proximal left subclavian artery stenosis in a prior coronary artery bypass graft
      patient.
AB  - Proximal subclavian artery stenosis may result in cardiac ischemia in coronary
      artery bypass graft patients with internal mammary grafts. We report a case of
      acute anterior myocardial infarction in such a patient who developed severe
      systemic hypotension. Symptoms and electrocardiographic changes resolved after
      proximal left subclavian artery stenting. Subclavian angiography should be
      considered in all prior coronary artery bypass graft patients with internal
      mammary grafts undergoing coronary angiography.

PMID- 19595404
TI  - Survival following acute complete occlusion of the left main coronary artery
      associated with major collateral from the right coronary artery.

PMID- 19595405
TI  - Molecular characterization of the genome of duck enteritis virus.
AB  - The genomic sequence of a strain of duck enteritis virus (DEV) was determined and
      analyzed in this study. The size of its genome is 158,091 bp in length and the
      genome is predicted to encode 78 putative proteins and resembles the members of
      the Alphaherpesvirinae in genomic organization and gene composition. The genome
      of the virus is composed of a unique long (UL) region, a unique short (US)
      region, a unique short internal repeat (IRS) region and a unique short terminal
      repeat (TRS) region. Its genomic arrangement pattern (UL-IRS-US-TRS) corresponds
      to D-type herpesvirus and is consistent with the members of Varicellovirus and
      Iltovirus genera. Sequence analysis reveals that the genome of the virus contains
      67 genes having homologs in most members of the Alphaherpesvirinae. Out of these
      genes, one gene has a homolog in cercopithecine herpesvirus 8 which is a virus of
      Betaherpesvirinae, and 5 genes have homologs in avian herpesviruses. Furthermore,
      the genome possesses three unique genes without homologs in any other
      herpesviruses. Like most members of the Alphaherpesvirinae, the genes in the UL
      region of its genome are well conserved, whereas the gene arrangement of IRS-US
      is similar to that of Marek's disease virus and equine herpesviruses 1.
      Therefore, our data based on the genomic analysis suggest that DEV represents an
      osculant taxonomic entity within the Alphaherpesvirinae.

PMID- 19595406
TI  - Cytoplasmic inclusion cistron of Soybean mosaic virus serves as a virulence
      determinant on Rsv3-genotype soybean and a symptom determinant.
AB  - Soybean mosaic virus (SMV; Potyvirus, Potyviridae) is one of the most widespread
      viruses of soybean globally. Three dominant resistance genes (Rsv1, Rsv3 and
      Rsv4) differentially confer resistance against SMV. Rsv1 confers extreme
      resistance and the resistance mechanism of Rsv4 is associated with late
      susceptibility. Here, we show that Rsv3 restricts the accumulation of SMV strain
      G7 to the inoculated leaves, whereas, SMV-N, an isolate of SMV strain G2,
      establishes systemic infection. This observation suggests that the resistance
      mechanism of Rsv3 differs phenotypically from those of Rsv1 and Rsv4. To identify
      virulence determinant(s) of SMV on an Rsv3-genotype soybean, chimeras were
      constructed by exchanging fragments between avirulent SMV-G7 and the virulent SMV
      N. Analyses of the chimeras showed that both the N- and C-terminal regions of the
      cytoplasmic inclusion (CI) cistron are required for Rsv3-mediated resistance.
      Interestingly, the N-terminal region of CI is also involved in severe symptom
      induction in soybean.

PMID- 19595407
TI  - RSV replication is attenuated by counteracting expression of the suppressor of
      cytokine signaling (SOCS) molecules.
AB  - Human RSV causes an annual epidemic of respiratory tract illness in infants and
      in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses
      include inhibition of type I IFN mRNA transcription and blocking signal
      transduction of JAK/STAT family members. The suppressor of cytokines signaling
      (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and
      block the activation of the JAK/STAT signaling pathway. To evaluate the potential
      of SOCS molecules to subvert the innate immune response to RSV infection, eight
      SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS
      mRNA expression in HEp-2 cells. Suppression of SOCS1, SOCS3 and CIS by short
      interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore,
      inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing
      STAT1/2 phosphorylation. These results suggest that RSV infection escapes the
      innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in
      epithelial cells.

PMID- 19595408
TI  - Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates
      with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA
      binding activity.
AB  - HTLV-I bZIP factor (HBZ) contains a C-terminal zipper domain involved in its
      interaction with c-Jun. This interaction leads to a reduction of c-Jun DNA
      binding activity and prevents the protein from activating transcription of AP-1
      dependent promoters. However, it remained unclear whether the negative effect of
      HBZ-SP1 was due to its weak DNA-binding activity or to its capacity to target
      cellular factors to transcriptionally-inactive nuclear bodies. To answer this
      question, we produced a mutant in which specific residues present in the
      modulatory and DNA-binding domain of HBZ-SP1 were substituted for the
      corresponding c-Fos amino acids to improve the DNA-binding activity of the c
      Jun/HBZ-SP1 heterodimer. The stability of the mutant, its interaction with c-Jun,
      DNA-binding activity of the resulting heterodimer, and its effect on the c-Jun
      activity were tested. In conclusion, we demonstrate that the repression of c-Jun
      activity in vivo is mainly due to the HBZ-SP1-mediated sequestration of c-Jun to
      the HBZ-NBs.

PMID- 19595409
TI  - Commerce and CAM--collaboration or competition?

PMID- 19595410
TI  - Anxiety as a factor influencing physiological effects of acupuncture.
AB  - PURPOSE: This study investigated the influence of manual acupuncture on heart
      rate variability and the role which anxiety can play in modifying physiological
      outcomes. METHOD: Analysis of heart rate variability (HRV) was used as a
      sensitive and a reliable indicator of the balance between sympathetic and
      parasympathetic regulation of the heartbeat. Two groups of healthy female
      subjects were recruited into the study. The control group (n=30) attended one
      experimental session where no acupuncture treatment was used. The experimental
      group (n=30) attended three sessions in which unilateral manual stimulation of
      acupuncture points LU7 and KD6 was performed. RESULTS: The stimulation of the
      acupuncture points LU7 and KD6 was not associated with significant changes in
      HRV. Previous familiarity with acupuncture did not influence the outcomes but
      level of anxiety had a strong impact on physiological outcomes. Stimulation of
      LU7 acupuncture point counterbalanced naturally occurring sympathetic increase
      over time and had relaxing and harmonizing effect on the heart rhythm without
      influencing subjective perception of increased anxiety. Stimulation of KD6
      acupuncture point had sympathetic influence on HRV in subjects with low "trait"
      anxiety and this influence was nullified by simultaneous stimulation of LU7
      acupuncture point. CONCLUSIONS: It seems likely that the level of anxiety can
      modify HRV during acupuncture treatment and up to 40 min after the treatment.
      Psychological factors such as anxiety level should be considered as having
      important influence on physiological response to acupuncture.

PMID- 19595411
TI  - Effects of stone spa (Ganban-yoku) on psychological states.
AB  - This uncontrolled intervention study explored the effects of stone spa use on the
      psychological states of women. Sixty-eight female volunteers (mean age 37.5 years
      (standard deviation 14.8)) recruited at a women-only stone spa facility
      participated in the study. They completed the short-form Profile of Moods States
      (POMS) and the State-Trait Anxiety Inventory (STAI) before and after stone spa
      use in order to determine changes in mood and anxiety states. Six factors
      relating to mood were measured using the POMS: Tension-Anxiety, Depression
      Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion. The two anxiety
      concepts of state anxiety and trait anxiety were also measured. The scores for
      Tension-Anxiety and Anger-Hostility and both anxiety measures were improved
      statistically after stone spa use. Stone spa use shows considerable promise for
      improving mood and reducing anxiety. Since this study was a descriptive,
      prospective and uncontrolled intervention study, further investigation of these
      promising findings is warranted.

PMID- 19595412
TI  - Journeying with Alice: some things I don't know for certain.
AB  - In this narrative I reflect on those things I do not know for certain. The
      narrative is constructed around my experience of giving Alice, a patient at the
      hospice where I worked as a complementary therapist, a foot massage. The
      narrative reveals the possibility of caring in the context of hospice, notably
      the significance of paying attention to little things such as a foot massage,
      that made such a difference to Alice's care. The narrative further reveals
      factors that resist caring, in particular the impact of labelling people as
      difficult for whatever reason. The narrative stands as an exemplar of reflective
      practice as an opportunity to reveal and challenge those things I might claim to
      know but which in the mystery of the human-human encounter can never be known for
      certain. Only by being non-attached to knowing can the practitioner truly realise
      her or his caring potential.

PMID- 19595413
TI  - Intentions and willingness to use complementary and alternative medicines: what
      potential patients believe about CAMs.
AB  - This paper explores the intentions and willingness of a sample of Australian
      consumers (N=356) to use complementary and alternative medicine (CAM).
      Participants considered using CAMs at least once in the next 2 months and rated
      the likelihood of certain consequences of CAM use, whether important others would
      approve, and if barriers would prevent them from using CAMs. People intending to
      use CAMs (high intenders) were more likely than those low on intention (low
      intenders) to endorse positive outcomes of CAM use and believe that important
      others would support their CAM use. High intenders were less likely than low
      intenders to believe that barriers would prevent use. Low intenders (n=200) were
      also asked to consider their response to a free CAM trial. Those willing to
      accept a trial were more likely than those unwilling to believe that CAMs could
      improve health and less likely to believe that laziness would prevent use. These
      results identify important beliefs which may influence people's decisions to use
      CAMs.

PMID- 19595414
TI  - Creating a therapeutic and healing environment with a pet therapy program.
AB  - BACKGROUND: Hospitalized patients encounter stressors that impact their
      experience and recovery. There is a need for theoretically-based, empirically
      supported nursing interventions to create a therapeutic and healing environment
      that decrease stress and improve patients' experiences. PURPOSE: To determine
      whether pet therapy interventions improve physiological, behavioral and mood
      outcomes and experiences of hospitalized patients. METHODS: A single group pre
      post-quasi-experimental design with mixed methods was used in 59 hospitalized
      patients. Paired t-tests were used to evaluate changes from baseline following a
      pet therapy intervention. Qualitative data were analyzed using content analysis.
      RESULTS: Compared with baseline, patients had significant decreases in pain,
      respiratory rate and negative mood state and a significant increase in perceived
      energy level. Quantitative and qualitative findings provide support for decreased
      tension/anxiety and fatigue/inertia and improved overall mood. CONCLUSIONS: Pet
      therapy is a low-tech, low-cost therapy that improved mood and was meaningful to
      hospitalized patients.

PMID- 19595415
TI  - Why do Norwegian nurses leave the public health service to practice CAM?
AB  - This paper explores a number of issues associated with the recent increase in
      nurses choosing to leave the Norwegian health care system in order to become
      independent practitioners of complementary and alternative medicine (CAM). The
      paper suggests that in Norway, nurses perceive medical hegemony continues to
      persist. Nurses perceive restrictions in their ability to develop their
      professional roles and status. CAM would appear to offer many nurses, the
      opportunity to develop their clinical skills in an autonomous, egalitarian and
      more holistic environment.

PMID- 19595416
TI  - Use of complementary and alternative medicine among patients with chronic
      diseases at outpatient clinics.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the use of
      complementary and alternative medicine among patients with chronic diseases at
      outpatient clinics. Another aim was to identify demographic and socio-economic
      factors that are associated with CAM use. RESEARCH DESIGN AND METHODS: Face-to
      face interviews of conveniently selected patients with chronic diseases were
      conducted in outpatient clinics of a general hospital. A validated data
      collection form was used to gather the information regarding pattern, perception,
      reasons, and perceived effect of CAM on the disease state. The other relevant
      information including demographics, diagnosis, indication, and treatment were
      collected from the patients' medical records. RESULTS: Out of 321 patients
      interviewed in this study, 205 patients were using some form of CAM, and thus the
      utilisation rate was 63.9%. A significant number of patients (35.5%) were using
      CAM for diabetes mellitus. Thirteen types of CAM were identified in the study
      with the most common being vitamins supplements (48.2%), herbal medicines
      (26.4%), ginseng (4.7%) and traditional Chinese medicine (4.0%). The patients
      with higher education level, higher income, and aged more than 50 years were
      independently associated with CAM use. Majority of the patients (77.6%) reported
      that their condition had improved by using CAM. CONCLUSION: The present study
      confirms the high frequency of CAM use among patients with chronic diseases in a
      Malaysian public hospital. The popularity of CAM indicated the patients'
      preference towards holistic approach to health care.

PMID- 19595417
TI  - Tactile massage within the primary health care setting.
AB  - This paper describes an observational study describing how Tactile Massage (TM)
      was integrated into Swedish clinical medical care, the impact of this initiative
      suggests a foundation for future research. Subjects completed three
      questionnaires pre- and post-tactile massage. These were: Sense of Coherence
      (SOC), an enlarged Health Index (HI) and the Borg CR10 scale. RESULTS: A
      convenience sample of forty-three subjects (37 women and 6 men) were referred to
      TM treatment for a range of problems including for pain, sleep disorders,
      inability to move, headache and tense body. Patients received 10 TM treatments,
      each lasting approx. 1h in length. The enlarged HI questionnaire indicated that
      eleven out of fourteen parameters were significantly affected according (p-values
      between 0.0015 and <0.001). These included energy, mood, tiredness, sleep, pain,
      movement, health, general health and physical health. Pain reduction was also
      significantly reduced using the Borg CR10 scale (p<0.001). CONCLUSION: TM seems
      to affect several dimensions of health, and this should be explored more fully in
      future research.

PMID- 19595418
TI  - Complementary therapists' motivation to work in cancer/supportive and palliative
      care: a multi-centre case study.
AB  - PURPOSE: To uncover complementary therapists' motivation to work in
      cancer/supportive and palliative care. METHOD: The study employed a multiple case
      study design, involving three cancer/supportive and palliative care settings in
      the North West of England. A questionnaire survey (n=51) was undertaken, followed
      by semi-structured interviews with a subgroup of the sample (n=28). RESULTS:
      Participants had a mean age of 50 years, were predominantly female and had varied
      career backgrounds, including prior professional experience in healthcare,
      teaching and private complementary therapy practice. Motivation for working in
      cancer/supportive and palliative care included vocational drive with a desire to
      provide individualised treatment and adopt a person centred, empowering and
      caring approach; disillusionment with conventional care; career development and
      personal experience of cancer or other serious illness. CONCLUSION: Findings
      indicated that motivational factors for therapists working in cancer
      care/supportive and palliative care were varied and highlighted a combination of
      'push and pull' factors, particularly for therapists who are also health care
      practitioners. Further research related to volunteering, sustainable services and
      support and training for therapists is required.

PMID- 19595419
TI  - A retrospective analysis of self-reported symptoms from 761 consecutive new
      patients presenting to a Neuro Emotional Technique chiropractic clinic.
AB  - PURPOSE: To describe the profile of patients presenting to a private chiropractic
      clinic specialising in Neuro Emotional Technique (NET) and to identify trends in
      the presentation of symptoms from these patients. METHODS: 761 consecutive new
      patients presented to a large, multi-doctor chiropractic clinic in which
      practitioners all adopt a similar philosophical paradigm and practice NET From
      January 2005 to December 2005, self-referred patients completed a new patient
      questionnaire, in which they self-reported one primary complaint for why they
      were visiting the practitioner. Predetermined patient information was entered
      manually into a database and basic descriptive statistics extracted. RESULTS:
      67.3% of participants were female and 32.6% of the participants were between the
      ages of 31 and 40. 54.8% of patients presented with a primary musculoskeletal
      complaint and 36.0% a non-musculoskeletal complaint. Of the musculoskeletal
      complaints, 40.8% of patients presented with back pain, 20.9% with neck pain and
      11.5% with shoulder pain. The most common form of non-musculoskeletal complaint
      was immune and recurrent infections (13.9%), stress and anxiety (12.8%) and
      depression (10.9%). 41.4% of participants reported a first time complaint,
      however, of the patients who had had the presenting complaint before 60.7%
      reported as having the complaint for greater than 1 year. Musculoskeletal and non
      musculoskeletal participants had similar pain profiles. CONCLUSION: This
      retrospective analysis is the first comprehensive description of the scope of NET
      patients and their presenting complaints. The patient profile of this NET clinic
      has a higher degree of non-musculoskeletal patients than that usually reported in
      non-NET chiropractic offices, and other forms of chiropractic previously
      described in the literature. Further cross sectional research is required to
      determine if this particular clinic is indicative of all NET practices and
      whether the presenting symptoms, especially the non-musculoskeletal, are resolved
      with NET.

PMID- 19595420
TI  - Complementary therapies, the placebo effect and the pharmacist.
AB  - Pharmacists need to know about complementary therapies so they can advise
      patients on their suitability, and also their compatibility with conventional
      drugs. This article discusses, from a pharmaceutical perspective, the types of
      therapies available, their applications and indications, and issues surrounding
      the placebo effect.

PMID- 19595422
TI  - Advanced treatment of biologically pretreated coking wastewater by
      electrochemical oxidation using boron-doped diamond electrodes.
AB  - Electrochemical oxidation is a promising technology to treatment of bio
      refractory wastewater. Coking wastewater contains high concentration of
      refractory and toxic compounds and the water quality usually cannot meet the
      discharge standards after conventional biological treatment processes. This paper
      initially investigated the electrochemical oxidation using boron-doped diamond
      (BDD) anode for advanced treatment of coking wastewater. Under the experimental
      conditions (current density 20-60mAcm(-2), pH 3-11, and temperature 20-60 degrees
      C) using BDD anode, complete mineralization of organic pollutants was almost
      achieved, and surplus ammonia-nitrogen (NH(3)-N) was further removed thoroughly
      when pH was not adjusted or at alkaline value. Moreover, the TOC and NH(3)-N
      removal rates in BDD anode cell were much greater than those in other common
      anode systems such as SnO(2) and PbO(2) anodes cells. Given the same target to
      meet the National Discharge Standard of China, the energy consumption of
      64kWhkgCOD(-1) observed in BDD anode system was only about 60% as much as those
      observed in SnO(2) and PbO(2) anode systems. Further investigation revealed that,
      in BDD anode cell, organic pollutants were mainly degraded by reaction with free
      hydroxyl radicals and electrogenerated oxidants (S(2)O(8)(2-), H(2)O(2), and
      other oxidants) played a less important role, while direct electrochemical
      oxidation and indirect electrochemical oxidation mediated by active chlorine can
      be negligible. These results showed great potential of BDD anode system in
      engineering application as a final treatment of coking wastewater.

PMID- 19595423
TI  - Investigation of the photocatalytic degradation pathway of the urine metabolite,
      creatinine: the effect of pH.
AB  - This study investigated the degradation pathway of creatinine (a urine
      metabolite) with immobilized titanium dioxide photocatalysts. The degradation of
      creatinine was studied at three different pH values (acidic, neutral and basic)
      in the absence of buffering solutions. The intermediates formed were identified
      by using electrospray ionization mass spectrometer (ESI-MS) in both negative and
      positive ion mode. Two distinct mechanistic pathways which govern the
      photocatalytic degradation of creatinine irrespective of the pH of the initial
      solution were identified. The initial solution pH affected only the selectivity
      between the two mechanisms. The primary oxidation steps of creatinine with
      hydroxyl radicals included demethylation, hydrogen abstraction, hydroxylation,
      oxidation, and ring opening. At acidic pH, additional transformation steps of the
      two mechanisms were identified. The intermediates detected in the positive ion
      mode, contained at least one atom of nitrogen in their structure, explaining the
      observed low nitrogen mineralization of creatinine with TiO(2) photocatalysis.
      The intermediates in the negative ion mode were low molecular weight organic
      acids that contained only carbon and hydrogen atoms.

PMID- 19595424
TI  - Removal of antimony(V) and antimony(III) from drinking water by coagulation
      flocculation-sedimentation (CFS).
AB  - Antimony occurs widely in the environment as a result of natural processes and
      human activity. Although antimony is similar to arsenic in chemical properties
      and toxicity, and a pollutant of priority interest to the USEPA and the EU, its
      environmental behaviors, control techniques, and even solution chemistry, are yet
      barely touched. In this study, antimony removal from drinking water with
      coagulation-flocculation-sedimentation (CFS) is comprehensively investigated with
      respect to the dependence of both Sb(III) and Sb(V) removal on the initial
      contaminant-loading level, coagulant type and dosage, pH and interfering ions.
      The optimum pH for Sb(V) removal with ferric chloride (FC) was observed at pH 4.5
      5.5, and continuously reduced with further pH increase. Over a broad pH range
      from 4.0 to 10.0, effective Sb(III) removal with FC was obtained. Contrary to the
      effective Sb removal with FC, the degree of both Sb(III) and Sb(V) removal with
      aluminum sulfate (AS) was very low, indicating the impracticability of AS
      application for antimony removal. The presence of phosphate and humic acid (HA)
      markedly impeded Sb(V) removal, while exhibited insignificant effect on Sb(III)
      removal. The effects of coagulant type, Sb species and pH are more pronounced
      than the effects of coagulant dose and initial pollutant concentration. After
      preliminarily excluding the possibility of precipitation and the predominance of
      coprecipitation, the adsorption mechanism is used to rationalize and simulate
      Sb/FC coagulation with good result by incorporating diffuse-layer model (DLM).

PMID- 19595425
TI  - Investigations of photochemical transformations of aqueous mercury: implications
      for water effluent treatment technologies.
AB  - Photochemical transformations of mercury were studied to determine its potential
      as a treatment mechanism to reduce mercury laden waters to trace concentrations.
      In this study, aqueous solutions of mercury nitrate in deionized water were
      exposed to UV irradiation and a gas purge. The impacts of purge gas (including
      rate and bubble size), UV irradiation wavelength, initial mercury concentration
      and time on mercury removal have been studied. Nitrogen purge with 254 nm UV
      irradiation resulted in the greatest net production of elemental mercury for all
      initial concentrations. These conditions followed pseudo first order kinetics and
      achieved the highest rate constant of 0.18s(-1). As oxygen was introduced into
      the solution, the quantity of elemental mercury volatilized decreased but still
      resulted in significant mercury losses through volatilization up to 90% in 60
      min. Overriding, the loss of elemental mercury from the solution is dependent
      upon the gas purge rate and bubble size.

PMID- 19595426
TI  - Validation and field testing of library-independent microbial source tracking
      methods in the Gulf of Mexico.
AB  - Water quality is frequently impacted by microbial pollution from human and animal
      feces. Microbial source tracking (MST) can identify dominant pollution sources
      and improve assessment of health risk compared to indicator bacteria alone. This
      study aims to standardize and validate MST methods across laboratories in coastal
      Gulf of Mexico states. Three laboratories evaluated library-independent MST
      methods for human sewage detection via conventional PCR: (1) human-associated
      Bacteroidales, (2) human polyomaviruses (HPyVs), and (3) Methanobrevibacter
      smithii. All methods detected targets in human sewage seeded into buffer,
      freshwater or marine water (100% sensitivity). The limit of detection (LOD) for
      human sewage was lowest for the Bacteroidales assay (10(-5)-10(-6) dilution).
      LODs for HPyVs and M. smithii assays were similar to each other (10(-3)-10(-4)),
      but were higher than Bacteroidales. The HPyVs assay was 100% specific, showing no
      cross-reactivity to dog, cow, cat, bird, or wild animal feces among >300 samples
      from three Gulf Coast regions. The human Bacteroidales assay was 96% specific,
      but cross-reacted with 10% of dog and some chicken samples. The M. smithii assay
      was 98% specific with limited cross-reactivity with cow, dog and seagull samples.
      An experts' workshop concluded that all methods showed sufficient accuracy and
      reliability to move forward. SOPs will be distributed to collaborating
      laboratories for further inter-laboratory comparison, and field validation will
      occur in year 2.

PMID- 19595427
TI  - Root uptake and reduction of hexavalent chromium by aquatic macrophytes as
      assessed by high-resolution X-ray emission.
AB  - Aquatic macrophytes Salvinia auriculata, Pistia stratiotes and Eichhornia
      crassipes were chosen to investigate the Cr(VI) reduced by root-based biosorption
      in a chromium uptake experiment, using a high-resolution XRF technique. These
      plants were grown in hydroponics medium supplied with non-toxic Cr concentrations
      during a 27-day metal uptake experiment. The high-resolution Cr-Kbeta
      fluorescence spectra for dried root tissues and Cr reference material (100% Cr,
      Cr(2)O(3), and CrO(3)) were measured using an XRF spectrometer. For all species
      of aquatic plant treated with Cr(VI), the energy of the Cr-Kbeta(2,5) line was
      shifted around 8 eV below the same spectral line identified for the Cr(VI)
      reference, but it was also near to the line identified for the Cr(III) reference.
      Moreover, there was a lack of the strong Cr-Kbeta'' line assigned to the Cr(VI)
      reference material within the Cr(VI)-treated plant spectra, suggesting the
      reduction of Cr(VI) for other less toxic oxidation states of Cr. As all Cr-Kbeta
      spectra of root tissue species were compared, the peak energies and lineshape
      patterns of the Cr-Kbeta(2,5) line are coincident for the same aquatic plant
      species, when they were treated with Cr(III) and Cr(VI). Based on the
      experimental evidence, the Cr(VI) reduction process has happened during metal
      biosorption by these plants.

PMID- 19595428
TI  - Sorption of dichlorodiphenyltrichloroethane (DDT) and its metabolites by
      activated carbon in clean water and sediment slurries.
AB  - Polyethylene-water partitioning coefficients (K(PE)) and mass transfer
      coefficients (k(PE)) for the ortho and para isomers of the organochlorine
      pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolites
      dichlorodiphenyldichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE) and,
      dichlorodiphenylmonochloroethylene (DDMU) were measured. These data were used to
      derive activated carbon (AC) sorption isotherms in clean water in the sub
      nanogram per litre free aqueous concentration range for a virgin and a
      regenerated AC. The sorption strength of AC for DDT and its metabolites was very
      high and logarithmic values of the AC-water partitioning coefficients, logK(AC),
      ranged from 8.47 to 9.26. A numerical mass transfer model was calibrated with
      this data to interpret previously reported reductions in DDT uptake by
      semipermeable membrane devices after AC amendment of sediment from Lauritzen
      Channel, California, USA. The activated carbon-water partitioning coefficient
      values (K(AC)) measured in clean water systems appear to overestimate the AC
      sorption capacity in sediment up to a factor 32 for DDT and its metabolites at
      long contact time with fine-sized AC. Modelling results show decreased
      attenuation of the AC sorption capacity with increased sediment-AC contact time.
      We infer that increased resistance in mass transfer of DDTs to sorption sites in
      the microporous region likely caused by deposits of dissolved organic matter in
      the macro- and mesopores of AC appears to be the most relevant fouling mechanism.
      These results suggest that DDTs may diffuse through possible deposits of
      dissolved organic matter over time, implying that the effects of sediment on the
      sorption of DDTs by AC may be more kinetic than competitive.

PMID- 19595429
TI  - Adsorption, sedimentation, and inactivation of E. coli within wastewater
      treatment wetlands.
AB  - Bacteria fate and transport within constructed wetlands must be understood if
      engineered wetlands are to become a reliable form of wastewater treatment. This
      study investigated the relative importance of microbial treatment mechanisms in
      constructed wetlands treating both domestic and agricultural wastewater.
      Escherichia coli (E. coli) inactivation, adsorption, and settling rates were
      measured in the lab within two types of wastewater (dairy wastewater lagoon
      effluent and domestic septic tank effluent). In situ E. coli inactivation was
      also measured within a domestic wastewater treatment wetland and the adsorption
      of E. coli was also measured within the wetland effluent. Inactivation of E. coli
      appears to be the most significant contributor to E. coli removal within the
      wastewaters and wetland environments examined in this study. E. coli survived
      longer within the dairy wastewater (DW) compared to the domestic wastewater
      treatment wetland water (WW). First order rate constants for E. coli inactivation
      within the WW in the lab ranged from 0.09 day(-1) (d(-1)) at 7.6 degrees C to
      0.18d(-1) at 22.8 degrees C. The average in situ rate constant observed within
      the domestic wetland ranged from 0.02 d(-1) to 0.03 d(-1) at an average water
      temperature of 17 degrees C. First order rate constants for E. coli inactivation
      within the DW ranged from 0.01 d(-1) at 7.7 degrees C to 0.04 d(-1) at 24.6
      degrees C. Calculated distribution coefficients (K(d)) were 19,000 mL g(-1),
      324,000 mL g(-1), and 293 mL g(-1) for E. coli with domestic septic tank effluent
      (STE), treated wetland effluent (WLE), and DW, respectively. Approximately 50%,
      20%, and 90% of E. coli were "free floating" or associated with particles <5
      microm in size within the STE, WLE, and DW respectively. Although 10-50% of E.
      coli were found to associate with particles >5 microm within both the STE and DW,
      settling did not appear to contribute to E. coli removal within sedimentation
      experiments, indicating that the particles the bacteria were associated with had
      very small settling velocities. The results of this study highlight the
      importance of wastewater characterization when designing a treatment wetland
      system for bacterial removal. This study illustrated the level of variability in
      E. coli removal processes that can be observed within different wastewater, and
      wetland environments.

PMID- 19595430
TI  - Oxone/Co(2+) oxidation as an advanced oxidation process: comparison with
      traditional Fenton oxidation for treatment of landfill leachate.
AB  - In this paper, the application of Fenton and Oxone/Co(2+) oxidation processes for
      landfill leachate treatment was investigated. The removal of the chemical oxygen
      demand (COD), suspended substances (SS) and the color of the landfill leachate by
      Fenton oxidation to that by Oxone/Co(2+) oxidation were compared under optimal
      operational conditions. For Fenton oxidation process, the optimal conditions were
      determined as: [H(2)O(2)]=80 mmol L(-1), [H(2)O(2)]/[Fe(2+)]=2.0, initial pH=2.5,
      reaction temperature=37.5+/-1 degrees C, reaction time=160 min, number of
      stepwise addition=3. Under the given conditions, 56.9% of the COD removal
      efficiency was achieved, but the SS and the color of the treated landfill
      leachate increased due to the generation of a large quantity of ferric hydroxide
      sludge. In reference to Oxone/Co(2+) oxidation process, the optimal conditions
      were determined as: [Oxone]=4.5 mmol L(-1), [Oxone]/[Co(2+)]=10(4), pH=6.5,
      reaction temperature=30+/-1 degrees C, reaction time=300 min, number of stepwise
      addition=7, the COD, SS and the color removal efficiencies were 57.5, 53.3 and
      83.3%, respectively. From this work, it can be concluded that Oxone/Co(2+)
      oxidation process demonstrated higher degradation efficiencies of the COD, SS and
      color for landfill leachate treatment than that by Fenton oxidation process. It
      also suggested that Oxone/Co(2+) oxidation process could be considered as one of
      the most promising technologies for practical applicability to treat landfill
      leachate in large scale. For further improving the efficiency of Oxone/Co(2+)
      oxidation process, we proposed that combination of it with other technologies in
      future such as ultraviolet, ultrasound and biological methods.

PMID- 19595431
TI  - Influence of operational conditions, waste input and ageing on contaminant
      leaching from waste incinerator bottom ash: a full-scale study.
AB  - Leaching of metals and Cl from fresh, naturally aged, and lab-scale aged bottom
      ashes generated during full-scale incineration experiments with different
      operational conditions (OC) and waste input (WI) was assessed. Although
      significant differences in the bulk contents of the generated bottom ashes were
      observed between the individual experiments, addition of 5.5 wt.% PVC, 11.1 wt.%
      chromated-copper-arsenate impregnated wood, 14.2 wt.% automotive shredder
      residue, 1.6 wt.% shoes, and 0.5 wt.% batteries to the normal municipal solid
      waste received at the incinerator (in six individual experiments) had no
      significant effect on metal leaching from the bottom ash. Likewise, changes in OC
      (furnace oxygen level and air distribution) could not be correlated to changes in
      leaching. The effects on metal leaching from ageing were generally larger than
      the effects from changes in OC and WI. Ash ageing caused a significant decrease
      in leaching of Cu, Zn, and Pb while leaching of Sb and particularly Cr increased.
      For Cl, a clear correlation between the bulk contents and leaching was observed
      for bottom ash generated in experiments with changes in WI. Comparison of
      leaching data obtained in this study with leaching from "typical" aged Danish
      bottom ash revealed no significant differences when the typical variations in
      leaching data over time and between different Danish incinerators were accounted.
      Generally, this indicates that metal leaching from bottom ash is not sensitive to
      limited changes in WI and OC as suggested in this paper, only Cl(-) leaching
      appeared to be affected.

PMID- 19595432
TI  - Accumulation, distribution and cellular partitioning of mercury in several
      halophytes of a contaminated salt marsh.
AB  - This work evaluates the role of a plant community in mercury (Hg) stabilization
      and mobility in a contaminated Portuguese salt marsh. With this aim, the
      distribution of Hg in below and aboveground tissues, as well as the metal
      partitioning between cellular fractions (soluble and insoluble) in four different
      species (Triglochin maritima L., Juncus maritimus Lam, Sarcocornia perennis
      (Miller) A.J. Scott, and Halimione portulacoides (L.) Aellen) was assessed.
      Mercury accumulation, translocation and compartmentation between organs and
      cellular fractions were related to the plant species. Results showed that the
      degree of Hg absorption and retention was influenced both by environmental
      parameters and metal translocation/partitioning strategies. Different plant
      species presented different allocation patterns, with marked differences between
      monocots (T. maritima and J. maritimus) and dicots (S. perennis, H.
      portulacoides). Overall, the two monocots, in particular T. maritima showed
      higher Hg retention in the belowground organs whereas the dicots, particularly S.
      perennis presented a more pronounced translocation to the aboveground tissues.
      Considering cellular Hg partitioning, all species showed a higher Hg binding to
      cell walls and membranes rather than in the soluble fractions. This strategy can
      be related to the high degree of tolerance observed in the studied species. These
      results indicate that the composition of salt marsh plant communities can be very
      important in dictating the Hg mobility within the marsh ecosystem and in the rest
      of the aquatic system as well as providing important insights to future
      phytoremediation approaches in Hg contaminated salt marshes.

PMID- 19595433
TI  - Estuarine sediment acute toxicity testing with the European amphipod Corophium
      multisetosum Stock, 1952.
AB  - This study assessed the use of the European amphipod Corophium multisetosum Stock
      [Stock, J.H., 1952. Some notes on the taxonomy, the distribution and the ecology
      of four species of the genus Corophium (Crustacea, Malacostraca). Beaufortia 21,
      1-10] in estuarine sediment acute toxicity testing. The sensitivity of adults to
      the reference toxicant CdCl(2) was determined in water-only 96 h exposures in
      salinity 2. LC(50) values ranged from 0.33mgCd(2+)L(-1) at 22 degrees C to
      0.57mgCd(2+)L(-1) at 15 degrees C. Adult survival was studied in control sediment
      with water salinity from 0 to 36 and with fine particles content (<63 microm)
      from 2% to 97% of total sediment, dry weight. Experiments were conducted at 15,
      18 and 22 degrees C and the results indicate that the species can be used under
      the full salinity range although higher mortality was observed at the lower
      salinity in the higher water temperature, and at the higher salinity in the lower
      water temperature. The species also tolerated the studied range of sediment fines
      content and showed the highest sensitivity at intermediate values of fines,
      especially at the higher temperature, thus advising that tests which have to
      accommodate sediments with a wide range in fines content should preferably be
      conducted at 15 degrees C rather than at 22 degrees C. The response in natural
      sediments was studied in samples collected yearly from 1997 to 2006, at a site
      located off the Tagus Estuary, western Portugal. A major flood event in winter
      2000-2001 induced detectable alterations in sediment baseline descriptors (grain
      size, redox potential and total volatile solids), organic contaminants (PAHs,
      PCBs, DDT metabolites and gamma-HCH) and the macrofauna benthic community.
      Mortality of the amphipod diminished significantly from the before to the after
      flood period, in close agreement with diminishing sediment contamination and
      increasing benthic fauna diversity, in the same time period. C. multisetosum is
      suitable to conduct acute sediment toxicity tests and presents good potential for
      the development of a full life-cycle sediment test, due to its amenability to
      laboratory culture and high survival in the control sediment.

PMID- 19595434
TI  - Physiological adaptations in the lichens Peltigera rufescens and Cladina
      arbuscula var. mitis, and the moss Racomitrium lanuginosum to copper-rich
      substrate.
AB  - Two lichen species (Peltigera rufescens and Cladina arbuscula subsp. mitis) and
      one moss species (Racomitrium lanuginosum) growing on a copper mine heaps
      (probably 200-300yr old) in the village of Spania dolina (Slovak Republic) were
      assessed for selected physiological parameters, including composition of
      assimilation pigments, chlorophyll a fluorescence, soluble proteins and free
      amino acid content. The lichen C. arbuscula subsp. mitis was collected also at a
      control locality where total copper concentration in the soil was approximately
      3% that of the waste heaps. Concentrations of Al, Co, Cu, Ni, Sb and Zn were
      highest in thalli of Peltigera, while the moss Racomitrium contained the highest
      content of Fe and Pb. Thalli of Cladina contained less metals than the
      cyanolichen Peltigera, and except for Zn metal concentrations in Cladina from the
      control locality were lower than in thalli of the same species from copper mine
      heaps. Regardless of the species or locality, the composition of assimilation
      pigments and chlorophyll a fluorescence showed that the tested lichens and moss
      were in good physiological condition and adapted to increased copper levels in
      the soil. There were significantly different amounts of total free amino acids in
      Peltigera, Cladina and Racomitrium from the Cu-polluted field. However,
      differences in amount of free amino acids in control, as well as Cu-polluted
      thalli of Cladina were less pronounced.

PMID- 19595435
TI  - The Central Society for Clinical Research: past, present, and future.

PMID- 19595436
TI  - Fat storage and the biology of energy expenditure.
AB  - Excessive adiposity results from an imbalance in energy homeostasis, whereby the
      consequences of excessive food intake are not balanced by increased energy
      expenditure. The increasing prevalence of excessive adiposity now involves more
      than 1 billion individuals worldwide. Of these, one half is obese and susceptible
      to comorbidities such as insulin resistance, type 2 diabetes, hyperlipidemia, and
      hypertension, which accelerate atherosclerosis. Lifestyle changes that have
      resulted largely in decreased physical activity now require a greater
      understanding of energy use that may allow better strategies for obesity control,
      because traditional methods of decreasing food intake and/or increasing exercise
      have not been successful without considerable behavioral counseling. This review
      focuses on the cell biology of white and brown fat tissue as well as on the
      central obesity that explains the comorbidities of the metabolic syndrome. Recent
      advances regarding the roles of central and autonomic nervous system regulation
      involved in fat remodeling are discussed, including the hypothalamic regulation
      of food intake and intestinal modulation, which affects satiety and peripheral
      energy expenditure. Finally, the new knowledge of cellular transcription factor
      regulation of energy expenditure is explained, whereby genes regulate
      mitochondriogenesis within adipocytes, liver, and muscle for both coupled and
      uncoupled oxidative phosphorylation-induced energy and heat expenditure,
      respectively. Newly discovered agonists of these transcription factors may now be
      realized that enhance energy expenditure. Strategies that combine such
      pharmacotherapies with lifestyle changes including enhanced physical activity and
      proper dietary intake may then provide the deterrents to excessive adiposity and
      its comorbidities, which now threaten human longevity.

PMID- 19595437
TI  - Premature vascular damage in systemic lupus erythematosus: an imbalance of damage
      and repair?
AB  - Systemic lupus erythematosus (SLE) is associated with an increase in the risk of
      premature cardiovascular complications caused by accelerated atherosclerosis,
      which significantly contributes to morbidity and mortality. Standard Framingham
      risk factors seem to be less important predictors of cardiovascular events than
      the presence of active SLE, and the immune dysregulation characteristic of lupus
      seems to play a dominant role in atherogenesis. Although both SLE-specific and
      nonspecific mechanisms have been proposed to play a prominent role in the
      induction of premature vascular damage in this disease, the exact etiology
      remains unclear. This review summarizes some of the proposed mechanisms that may
      promote accelerated vascular damage in lupus and explores potential targets for
      cardiovascular risk prevention in this patient population.

PMID- 19595438
TI  - Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper
      by tetrathiomolybdate and a comparison with trientine.
AB  - It has become clear that serum "free" copper (the copper not bound to
      ceruloplasmin in the blood) is the copper causing copper toxicity in Wilson's
      disease. But up until now, free copper has not been closely followed during
      initiation of anticopper therapy in neurologically presenting patients. During
      this period of initial therapy, the future fate of these patients hangs in the
      balance-if they worsen neurologically as often happens with penicillamine or
      trientine therapy, many never recover. We hypothesize that free copper levels are
      a biological marker of clinical outcome in these patients. In this article, we
      evaluate the control of free copper in 3 studies of initial anticopper treatment
      in neurologically presenting Wilson's disease patients. The first (study 1) is a
      55-patient open-label trial of tetrathiomolybdate, the second (study 2) is a 48
      patient double-blind trial comparing tetrathiomolybdate and trientine, and the
      third (study 3) is a 40-patient double-blind comparison of 2 disease regimens of
      tetrathiomolybdate. Free copper levels were determined by subtracting
      ceruloplasmin and tetrathiomolybdate bound copper from total serum copper.
      Tetrathiomolybdate showed very strong control of free copper levels over the 8
      weeks of treatment in the 55-patient open-label study (study 1), reducing it to a
      mean value of about one fourth, or less, of baseline. In the
      tetrathiomolybdate/trientine double blind (study 2), tetrathiomolybdate again
      showed good control of free copper levels over 8 weeks of treatment, which is
      significantly better than trientine. In the trientine arm of study 2, mean free
      copper levels actually went up during trientine therapy. The 5 patients who
      neurologically worsened on trientine therapy over 8 weeks of treatment showed
      significant spikes in serum free copper levels associated in time with their
      neurologic worsening. Patients who did not worsen neurologically generally did
      not show significant spikes in free copper. Tetrathiomolybdate controlled copper
      less well in the dose regimen study (study 3) than in the previous 2 studies of
      tetrathiomolybdate treatment, probably because of a change in the way "away from
      food" tetrathiomolybdate was given.

PMID- 19595439
TI  - Association of medical noncompliance and long-term adverse outcomes, after
      myocardial infarction in a minority and uninsured population.
AB  - The association of noncompliance with evidence-based medical therapies after
      myocardial infarction (MI) on long-term outcomes is not well recognized in
      minority and uninsured populations. Consecutive MI patients at a large urban
      hospital were followed for compliance with evidence-based medications (aspirin,
      clopidogrel, statins, beta blockers, and angiotensin converting enzyme inhibitors
      [ACEIs]/angiotensin receptor blockers [ARBs]). Noncompliance was defined as
      proportion of days covered < or =80%. The outcome was combined mortality and MI.
      Kaplan-Meier analyses were used to explore the impact of noncompliance > or =4
      medications. Of the 509 patients (86% minorities, 77% uninsured, and 54%
      diabetics), 132 (25.9%) presented with ST segment elevation with myocardial
      infarction (STEMI) and 377 (74.1%) with a non-ST segment elevation with
      myocardial infarction (NSTEMI), revascularization was performed in 297 (58.4%)
      patients, 72 (14.2%) patients died, 22 (4.3%) patients had an MI, and 91 (17.9%)
      patients had either event at a median follow-up of 2 (0.5-2.9) years.
      Noncompliance > or = 4 medications was significantly associated with adverse
      survival compared with compliant patients (29.7% vs 78.9%). After adjusting for
      traditional risk factors, The Global Registry of Acute Coronary Events risk score
      for predicting death during 6 months post-discharge, revascularization, left
      ventricular (LV) function, coronary artery disease (CAD) severity, and punctual
      clinic visits, noncompliance with > or = 4 evidence-based medications was an
      independent factor associated with death or MI (hazard ratio [HR], 2.83; 95%
      confidence interval [CI]=1.60-5.01) in this minority and uninsured population.

PMID- 19595441
TI  - Effects of ethanol-blended gasoline on air pollutant emissions from motorcycle.
AB  - The effect of ethanol-gasoline blends on criteria air pollutant emissions was
      investigated in a four-stroke motorcycle. The ethanol was blended with unleaded
      gasoline in four percentages (3, 10, 15, and 20% v/v) and controlled at a
      constant research octane number, RON (95), to accurately represent commercial
      gasoline. CO, THC, and NOx emissions were evaluated using the Economic Commission
      for Europe cycle on the chassis dynamometers. The results of the ethanol-gasoline
      blends were compared to those of commercial unleaded gasoline with methyl tert
      butyl ether as the oxygenated additive. In general, the exhaust CO and NOx
      emissions decreased with increasing oxygen content in fuels. In contrast, ethanol
      added in the gasoline did not reduce the THC emissions for a constant RON
      gasoline. The 15% ethanol blend had the highest emission reductions relative to
      the reference fuel. The high ethanol-gasoline blend ratio (20%) resulted in a
      less emission reduction than those of low ratio blends (<15%). This may be
      attributed to the changes in the combustion conditions in the carburetor engine
      with 20% ethanol addition. Furthermore, the influence of ethanol-gasoline blends
      on the reduction of exhaust emissions was observed at different driving modes,
      especially at 15km/h cruising speed for CO and THC and acceleration stages for
      NOx.

PMID- 19595440
TI  - Stimulation of sensory neurons improves cognitive function by promoting the
      hippocampal production of insulin-like growth factor-I in mice.
AB  - Calcitonin gene-related peptide (CGRP) increases the production of insulin-like
      growth factor-I (IGF-I) in the mouse brain. IGF-I exerts beneficial effects on
      the cognitive function by increasing synaptic transmission and by inducing
      angiogenesis and neurogenesis in the hippocampus. In the current study, we
      examined whether stimulation of sensory neurons by capsaicin improved the
      cognitive function by increasing the production of IGF-I in the hippocampus using
      wild-type (WT) and CGRP-knockout (CGRP-/-) mice. Significant increases of the
      hippocampal tissue levels of CGRP, IGF-I, and IGF-I messenger RNA (mRNA) were
      observed after capsaicin administration in WT mice (P < 0.01) but not in CGRP-/-
      mice. Increase in the expression of c-fos was also observed in the spinal dorsal
      horn, the parabrachial nuclei, and the hippocampus after capsaicin administration
      in WT mice but not in CGRP-/- mice. Significant enhancement of angiogenesis and
      neurogenesis was observed in the dentate gyrus of the hippocampus after capsaicin
      administration in WT mice (P < 0.01) but not in CGRP-/- mice. Although capsaicin
      administration improved spatial learning in WT mice, no such effect was observed
      in CGRP-/- mice. Capsaicin-induced improvement of the spatial learning was
      reversed by administration of an anti-IGF-I antibody and by that of a CGRP
      receptor antagonist CGRP (8-37) in WT mice. The administration of IGF-I improved
      the spatial learning in both WT and CGRP-/- mice. These observations strongly
      suggest that the stimulation of sensory neurons by capsaicin might increase IGF-I
      production via increasing the hippocampal tissue CGRP levels, and it may thereby
      promote angiogenesis and neurogenesis to produce improvement of the cognitive
      function in mice.

PMID- 19595442
TI  - Cyclic nucleotides inhibit MAP kinase activity in low-dose collagen-stimulated
      platelets.
AB  - Collagen-induced platelet activation is a complex process involving multiple
      signaling pathways. The role(s) of MAP kinases (ERKs and p38(MAPK)) are unclear,
      although at high, but not low, collagen concentrations p38(MAPK) is involved in
      cPLA(2)-mediated arachidonic acid release, prior to thromboxane generation.
      Cyclic nucleotides are conventionally regarded as mediators of platelet
      inhibition. However recent studies suggested a role for cGMP early in a MAP
      kinase pathway in platelet activation. In the current study the roles and
      relationships of MAP kinases, cyclic nucleotides and cPLA(2) in platelet
      activation by low-dose collagen and a thromboxane analogue (U46619) have been
      evaluated. Stimulants of neither adenylate cyclase (PGI(2)) nor guanylate cyclase
      (NaNP) alone had any effect on the basal phosphorylation of either MAP kinase.
      PGI(2) inhibited ERK/p38(MAPK) phosphorylation in response to both agonists which
      was unaffected by a cPLA(2) inhibitor (AACOCF(3)). NaNP inhibited collagen
      induced ERK/p38(MAPK) phosphorylation, which was enhanced by AACOCF(3) and
      reversed by a guanylate cyclase inhibitor (ODQ). However NaNP had no effect on
      U46619-induced p38(MAPK) phosphorylation. Thus adenylate cyclase activation
      inhibits low-dose collagen-induced MAP kinase phosphorylation both prior, and
      distal, to thromboxane release. The study also supports an inhibitory, rather
      than stimulatory, role for guanylate cyclase in platelet signaling.

PMID- 19595443
TI  - Early postabortion recovery of Neospora-infected lactating dairy cows.
AB  - This study was designed to assess the reproductive performance of Neospora
      caninum-infected dairy cows (Bos taurus) after abortion. The population examined
      was composed of 92 aborting cows subsequently subjected to at least one
      artificial insemination (AI) attempt. Of these animals, 68 were N. caninum
      seropositive and 24 were seronegative. Only animals producing at least 25 kg milk
      at the estrus after abortion were inseminated. Normal uterine involution was
      verified at first AI after abortion in cows showing estrous signs within 30 d of
      abortion. Of the 92 aborting cows, 73 (79.3%) became pregnant after abortion: 57
      (83.8%) and 16 (66.7%) of the N. caninum seropositive and seronegative cows,
      respectively. The factors days of gestation and lactation number at abortion
      failed to differ between the two Neospora serostatus groups, based on Student's t
      test or Kruskal-Wallis tests, respectively. The interval from abortion to first
      AI, the number of AIs necessary for an animal to become pregnant, and the
      interval from abortion to next pregnancy in cows becoming pregnant were lower for
      the N. caninum-seropositive than for the N. caninum-seronegative cows (P<0.0001).
      Logistic regression analysis indicated no significant effects of herd, lactation
      number, days of gestation at abortion, and the interval from abortion to AI on
      the likelihood of pregnancy at first AI after abortion. Based on the odds ratio,
      Neospora-seropositive cows were 6.22 times more likely to become pregnant at
      first AI after abortion compared with their seronegative partners. Fifty-three of
      the Neospora-seropositive cows (78%) were inseminated within 30 d after abortion
      and 26 (49%) became pregnant, whereas only one seronegative cow (4.2%) was ready
      for insemination within this 30-d period and remained open after first AI. These
      results indicate that Neospora-infected cows suffering abortion can be
      inseminated with a likelihood of high fertility within the first month of
      abortion. We recommend checking that uterine involution is normal early after
      abortion in N. caninum-seropositive cows.

PMID- 19595444
TI  - Strength of tunnel-restored teeth with different materials and marginal ridge
      height.
AB  - OBJECTIVE: The aim of the study was to investigate the strength of the marginal
      ridge of tunnel preparations with different marginal ridge heights, using
      different restorative materials. MATERIALS AND METHODS: 120 sound premolars were
      randomly divided into three groups of standardized tunnel preparations with a
      remaining marginal ridge height of 1.5 mm, 2.5 mm and 3.5 mm, respectively. In
      each tunnel group, 10 teeth were filled with all four newly developed adhesive
      materials that had not previously been used in tunnel preparation: Ketac Aplicap,
      Fuji IX, Fuji II LC and Beautifil Flow F02. The control group comprised 10 sound
      teeth. All teeth were subjected to incremental dynamic force testing. Remaining
      marginal ridge height and restoration material were the independent variables.
      The mean maximum energy (MEI) score was the dependent variable. Data were
      analyzed, using one- and two-way analysis of variance. Scheffe's test and
      Student's t-test were used for comparison between groups. RESULTS: Both
      restorative material (P<0.0001) and remaining marginal ridge height (P<0.0001)
      had a statistically significant effect on the mean MEI score of tunnel-prepared
      teeth. At the 2.5 mm of remaining marginal ridge height, no statistically
      significant difference in mean MEI score existed between Beautifil Flow F02
      filled tunnel-prepared teeth and sound teeth. SIGNIFICANCE: Premolars tunnel
      restored with Beautifil Flow F02 at 2.5 mm distance from the marginal ridge were
      as strong as sound teeth.

PMID- 19595445
TI  - Oxygen inhibition and incremental layer bond strengths of resin composites.
AB  - OBJECTIVES: When dentists light cure resin composite restorations in increments
      or after contouring the surface layer to shape with a hand instrument the surface
      layer is exposed to air during polymerization. The presence of an oxygen
      inhibited resin surface layer may impact on clinical performance. Conflicting
      data has been produced in vitro regarding this topic. METHODS: To shed further
      light on this subject the current investigation assessed the thickness of the
      oxygen inhibited layer (OIL) and subsequent interfacial bond strength at various
      times post-cure of an "initial increment" for a range of experimental and
      commercial resin composites. The latter included conventional methacrylate-based
      composites and a novel low shrink Silorane resin chemistry product. RESULTS: A
      decrease in composite viscosity brought about by an increase in diluent monomer
      content in the matrix for the experimental composite formulations led to increase
      in OIL thickness. The OIL surface layer thickness for the commercial methacrylate
      based RBC specimens cured in air were 19.2+/-6.3 and 13.8+/-5.3 microm,
      respectively and 9.0+/-6.6 microm for Silorane. No test material exhibited a
      measurable OIL thickness polymerized in the nitrogen atmosphere. SIGNIFICANCE:
      From the current findings it may be concluded that incremental bond strength is
      not wholly reliant on surface inhibition since no differences in bond strength
      following immediate placement were observed between air and nitrogen atmosphere
      for any experimental or commercial material. For large restorations requiring
      multiple increments which are placed on fresh material, the bond strength between
      successive layers of Silorane should be no different to conventional methacrylate
      materials. Repair and bonding to aged Silorane restorations may be more
      problematic as inferior incremental bond strengths ensued when addition was
      delayed.

PMID- 19595446
TI  - Bonding effectiveness and interfacial characterization of a nano-filled resin
      modified glass-ionomer.
AB  - Glass-ionomers (GIs) exhibit excellent clinical bonding effectiveness, but still
      have shortcomings such as polishability and general aesthetics. The aims of this
      study were (1) to determine the micro-tensile bond strength (microTBS) to enamel
      and dentin of a nano-filled resin-modified GI (nano-RMGI; Ketac N100, 3M-ESPE),
      and (2) to characterize its interfacial interaction with enamel and dentin using
      transmission electron microscopy (TEM). METHODS: The nano-RMGI was used both with
      and without its primer, while a conventional RMGI restorative material (conv
      RMGI; Fuji II LC, GC) and a packable conventional GI cement (conv-GI; Fuji IX GP,
      GC) were used as controls. After bonding to freshly extracted human third molars,
      microspecimens of the interfaces were machined into a cylindrical hourglass shape
      and tested to failure in tension. Non-demineralized TEM sections were prepared
      and examined from additional teeth. RESULTS: The microTBS to both enamel and
      dentin of nano-RMGI and conv-GI were not statistically different; the microTBS of
      non-primed nano-RMGI was significantly lower, while that of conv-RMGI was
      significantly higher than that of all other groups. TEM of nano-RMGI disclosed a
      tight interface at enamel and dentin without surface demineralization and hybrid
      layer formation. A thin filler-free zone (<1 microm) was formed at dentin. A high
      filler loading and effective filler distribution were also evident, with
      localized areas exhibiting nano-filler clustering. CONCLUSIONS: The nano-RMGI
      bonded as effectively to enamel and dentin as conv-GI, but bonded less
      effectively than conv-RMGI. Its bonding mechanism should be attributed to micro
      mechanical interlocking provided by the surface roughness, most likely combined
      with chemical interaction through its acrylic/itaconic acid copolymers.

PMID- 19595448
TI  - The unchanging mortality gap for people with schizophrenia.

PMID- 19595447
TI  - 11-year follow-up of mortality in patients with schizophrenia: a population-based
      cohort study (FIN11 study).
AB  - BACKGROUND: The introduction of second-generation antipsychotic drugs during the
      1990s is widely believed to have adversely affected mortality of patients with
      schizophrenia. Our aim was to establish the long-term contribution of
      antipsychotic drugs to mortality in such patients. METHODS: Nationwide registers
      in Finland were used to compare the cause-specific mortality in 66 881 patients
      versus the total population (5.2 million) between 1996, and 2006, and to link
      these data with the use of antipsychotic drugs. We measured the all-cause
      mortality of patients with schizophrenia in outpatient care during current and
      cumulative exposure to any antipsychotic drug versus no use of these drugs, and
      exposure to the six most frequently used antipsychotic drugs compared with
      perphenazine use. FINDINGS: Although the proportional use of second-generation
      antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life
      expectancy between patients with schizophrenia and the general population did not
      widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use
      of perphenazine, the highest risk for overall mortality was recorded for
      quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest
      risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between
      clozapine vs perphenazine, and p<0.0001 for all other antipsychotic drugs). Long
      term cumulative exposure (7-11 years) to any antipsychotic treatment was
      associated with lower mortality than was no drug use (0.81, 0.77-0.84). In
      patients with one or more filled prescription for an antipsychotic drug, an
      inverse relation between mortality and duration of cumulative use was noted (HR
      for trend per exposure year 0.991; 0.985-0.997). INTERPRETATION: Long-term
      treatment with antipsychotic drugs is associated with lower mortality compared
      with no antipsychotic use. Second-generation drugs are a highly heterogeneous
      group, and clozapine seems to be associated with a substantially lower mortality
      than any other antipsychotics. Restrictions on the use of clozapine should be
      reassessed. FUNDING: Annual EVO Financing (Special government subsidies from the
      Ministry of Health and Welfare, Finland).

PMID- 19595449
TI  - Targeted intracellular codelivery of chemotherapeutics and nucleic acid with a
      well-defined dendrimer-based nanoglobular carrier.
AB  - Codelivery of different therapeutics has a potential to efficaciously treat human
      diseases via their synergetic effects. We have recently developed a new class
      dendrimers, poly(l-lysine) dendrimers with a silsesquioxane cubic core
      (nanoglobules). These dendrimers have compact globular and well-defined
      structures and highly functionalized surfaces, and can be used as versatile
      carriers for biomedical applications. In this study, a generation-3 (G3)
      nanoglobular dendrimer was used to conjugate a peptide c(RGDfK) with a PEG spacer
      for codelivery of doxorubicin (DOX) and siRNA. Doxorubicin (DOX) was coupled to
      the RGD targeted nanoglobule via a degradable disulfide spacer to give G3-[PEG
      RGD]-[DOX]. G3-[PEG-RGD]-[DOX] showed higher cytotoxicity than free DOX at high
      doses in glioblastoma U87 cells. G3-[PEG-RGD]-[DOX] was further complexed with
      siRNA and such complexes were readily internalized by U87 cells as shown by
      confocal microscopy. The siRNA complexes of the targeted conjugate resulted in
      significantly higher gene silencing efficiency in U87-Luc cells than those of
      control conjugates G3-[PEG-RGD] and G3-[DOX]. The nanoglobules are promising
      carriers for the codelivery of nucleic acids and chemotherapeutic agents.

PMID- 19595450
TI  - Time-dependent degradation of titanium osteoconductivity: an implication of
      biological aging of implant materials.
AB  - The shelf life of implantable materials has rarely been addressed. We determined
      whether osteoconductivity of titanium is stable over time. Rat bone marrow
      derived osteoblasts were cultured on new titanium disks (immediately after acid
      etching), 3-day-old (stored after acid-etching for 3 days in dark ambient
      conditions), 2-week-old, and 4-week-old disks. Protein adsorption capacity, and
      osteoblast migration, attachment, spread, proliferation and mineralization
      decreased substantially on old titanium surfaces in an age-dependent manner. When
      the 4-week-old implants were placed into rat femurs, the biomechanical strength
      of bone-titanium integration was less than half that for newly processed implants
      at the early healing stage. More than 90% of the new implant surface was covered
      by newly generated bone compared to 58% for 4-week-old implants. This time
      dependent biological degradation was also found for machined and sandblasted
      titanium surfaces and was associated with progressive accumulation of hydrocarbon
      on titanium surfaces. The new surface could attract osteoblasts even under a
      protein-free condition, but its high bioactivity was abrogated by masking the
      surface with anions. These results uncover an aging-like time-dependent
      biological degradation of titanium surfaces from bioactive to bioinert. We also
      suggest possible underlying mechanisms for this biological degradation that
      provide new insights into how we could inadvertently lose, and conversely,
      maximize the osteoconductivity of titanium-based implant materials.

PMID- 19595451
TI  - Dynamic cell culturing and its application to micropatterned, elastin-like
      protein-modified poly(N-isopropylacrylamide) scaffolds.
AB  - In this study a tissue engineering scaffold was constructed from poly(N
      isopropylacrylamide) (pNIPAM) to study the influence of strain on cell
      proliferation and differentiation. The effect of surface chemistry and topography
      on bone marrow mesenchymal stem cells was also investigated. Micropatterned
      pNIPAM films (channels with 10 microm groove width, 2 microm ridge width, 20
      microm depth) were prepared by photopolymerization. The films were chemically
      modified by adsorption of a genetically engineered and temperature sensitive
      elastin-like protein (ELP). Dynamic conditions were generated by repeated
      temperature changes between 29 degrees C and 37 degrees C. ELP presence on the
      films enhanced initial cell attachment two fold (Day 1 cell number on films with
      ELP and without ELP were 27.6 x 10(4) and 13.2 x 10(4), respectively) but had no
      effect on proliferation in the long run. ELP was crucial for maintaining the
      cells attached on the surface in dynamic culturing (Day 7 cell numbers on the
      films with and without ELP were 81.4 x 10(4) and 12.1 x 10(4), respectively) and
      this enhanced the ability of pNIPAM films to transfer mechanical stress on the
      cells. Dynamic conditions improved cell proliferation (Day 21 cell numbers with
      dynamic and with static groups were 180.4 x 10(4) and 157.7 x 10(4),
      respectively) but decreased differentiation (Day 14 specific ALP values on the
      films of static and dynamic groups were 6.6 and 3.5 nmol/min/cell, respectively).
      Thus, a physically and chemically modified pNIPAM scaffold had a positive
      influence on the population of the scaffolds under dynamic culture conditions.

PMID- 19595453
TI  - Protein adsorption and clotting time of pHEMA hydrogels modified with C18 ligands
      to adsorb albumin selectively and reversibly.
AB  - This work intended to create a nanostructured biomaterial that would bind albumin
      in a selective and reversible way in order to inhibit the adsorption of other
      blood proteins and therefore minimize activation of coagulation. Different levels
      of C18 ligand have been immobilized on poly(2-hydroxyethyl methacrylate) (pHEMA).
      We hypothesize that samples with intermediate amounts of C18 ligand would allow
      albumin to recognize them and bind through its hydrophobic pockets specific for
      long chain fatty acids. Surface characterization has confirmed increasing amounts
      of C18 ligand on pHEMA as the percentage of C18 in solution increases, with
      maximum coverage achieved in 10% C18 samples. Adsorption from pure albumin
      solution revealed a small decrease in albumin adsorption from pHEMA to 1% C18 and
      2.5% C18 samples, but on surfaces with 5% or higher C18 the amount of adsorbed
      albumin increased as the percentage of C18 increased. Competitive adsorption
      studies in the presence of both albumin and fibrinogen, and in the presence of
      all plasma proteins showed that 1% C18 and 2.5% C18 were the only surfaces
      selective for albumin, and that the presence of all plasma proteins may even
      potentiate albumin adsorption. Reversibility studies demonstrated that both 2.5%
      C18 and 5% C18 samples exchange (125)I-albumin selectively in the presence of
      both unlabeled albumin and plasma, but 2.5% C18 samples presented higher
      exchangeability rates (58%). Clotting times using recalcified plasma revealed
      that samples with none or small amounts of C18 (pHEMA to 5% C18) did not shorten
      the clotting time compared to the negative control (polystyrene), indicating low
      activation of the intrinsic coagulation cascade.

PMID- 19595452
TI  - Mechanosensitivity of fibroblast cell shape and movement to anisotropic
      substratum topography gradients.
AB  - In this report, we describe using ultraviolet (UV)-assisted capillary force
      lithography (CFL) to create a model substratum of anisotropic micro- and
      nanotopographic pattern arrays with variable local density for the analysis of
      cell-substratum interactions. A single cell adhesion substratum with the constant
      ridge width (1 microm), and depth (400 nm) and variable groove widths (1-9.1
      microm) allowed us to characterize the dependence of cellular responses,
      including cell shape, orientation, and migration, on the anisotropy and local
      density of the variable micro- and nanotopographic pattern. We found that
      fibroblasts adhering to the denser pattern areas aligned and elongated more
      strongly along the direction of ridges, vs. those on the sparser areas,
      exhibiting a biphasic dependence of the migration speed on the pattern density.
      In addition, cells responded to local variations in topography by altering
      morphology and migrating along the direction of grooves biased by the direction
      of pattern orientation (short term) and pattern density (long term), suggesting
      that single cells can sense the topography gradient. Molecular dynamic live cell
      imaging and immunocytochemical analysis of focal adhesions and actin cytoskeleton
      suggest that variable substratum topography can result in distinct types of
      cytoskeleton reorganization. We also demonstrate that fibroblasts cultured as
      monolayers on the same substratum retain most of the properties displayed by
      single cells. This result, in addition to demonstrating a more sophisticated
      method to study aspects of wound healing processes, strongly suggests that even
      in the presence of adhesive cell-cell interactions, the cues provided by the
      underlying substratum topography continue to exercise substantial influence on
      cell behavior. The described experimental platform might not only further our
      understanding of biomechanical regulation of cell-matrix interactions, but also
      contribute to bioengineering of devices with the optimally structured design of
      cell-material interface.

PMID- 19595454
TI  - Single-cell hydrogel encapsulation for enhanced survival of human marrow stromal
      cells.
AB  - Inadequate extracellular matrix cues and subsequent apoptotic cell death are
      among crucial factors currently limiting cell viability and organ retention in
      cell-based therapeutic strategies for vascular regeneration. Here we describe the
      use of a single-cell hydrogel capsule to provide enhanced cell survival of
      adherent cells in transient suspension culture. Human marrow stromal cells
      (hMSCs) were singularly encapsulated in agarose capsules containing the
      immobilized matrix molecules, fibronectin and fibrinogen to ameliorate cell
      matrix survival signals. MSCs in the enriched capsules demonstrated increased
      viability, greater metabolic activity and enhanced cell-cytoskeletal patterning.
      Increased cell viability resulted from the re-induction of cell-matrix
      interactions likely via integrin clustering and subsequent activation of the
      extracellular signal regulated MAPK (ERK)/mitogen activated protein kinase (MAPK)
      signaling cascade. Proof of principle in-vivo studies, investigating autologous
      MSC delivery into Fisher 344 rat hindlimb, depicted a significant increase in the
      number of engrafted cells using the single-cell encapsulation system.
      Incorporation of immobilized adhesion molecules compensates, at least in part,
      for the missing cell-matrix cues, thereby attenuating the initial anoikis stimuli
      and providing protection from subsequent apoptosis. Thus, this single-cell
      encapsulation strategy may markedly enhance therapeutic cell survival in targeted
      tissues.

PMID- 19595455
TI  - Methylene blue-encapsulated phosphonate-terminated silica nanoparticles for
      simultaneous in vivo imaging and photodynamic therapy.
AB  - A bifunctional nanoparticles-based carrier for simultaneous in vivo imaging and
      photodynamic therapy by encapsulating methylene blue (MB) alone in the
      phosphonate-terminated silica matrix has been developed. The phosphonate
      terminated silica nanoparticles, entrapping water-soluble photosensitizer MB (MB
      encapsulated PSiNPs), are synthesized by the controlled synchronous hydrolysis of
      tetraethoxysilane and trihydroxyl silyl propyl methyl phosphonate in the water-in
      oil microemulsion. The resulting MB-encapsulated PSiNPs effectively prevent the
      leakage of entrapped MB from the particles and provide protection for against
      reduction by diaphorase. Enough dose of irradiation to the MB-encapsulated PSiNPs
      under the light of 635 nm results in efficient generation of singlet oxygen and
      induces photodynamic damage to Hela cells. Furthermore, the non-invasive
      visualization of MB-encapsulated PSiNPs in mice under the in vivo imaging system
      confirmed the MB-encapsulated PSiNPs also presents near-infrared luminescence for
      in vivo imaging. And the effect of the PDT toward the xenograft tumor in vivo is
      exciting after imaging the MB-encapsulated PSiNPs injected tumor using in vivo
      optical imaging system. Thus, the single particle platform is effective for
      simultaneous in vivo imaging and photodynamic therapy without using extra agent,
      which can provide image-guidance for site-specific photodynamic therapy.

PMID- 19595456
TI  - Multiple factor interactions in biomimetic mineralization of electrospun
      scaffolds.
AB  - One of the major limitations in scaffold-based bone tissue engineering has been
      the inability to increase the loading of biologically active inorganic mineral.
      The present study introduces a novel two step strategy to increase overall
      mineral content of electrospun scaffolds and employs multiple factor interaction
      as a statistic to identify the combination of factors that yields maximal
      scaffold mineralization. Different amounts of nHA (0, 10, 25 and 50% by wt. of
      polymer) were electrospun in combination with polydioxanone (PDO) or
      poly(glycolide: lactide) to generate composite scaffolds. Successful
      incorporation of nHA within, on and in between nanofibers was confirmed by
      transmission and scanning electron microscopy. These scaffolds were immersed in
      different types (conventional, revised, ionic and modified) of simulated body
      fluid (SBF), prepared at 1x and 4x concentrations and the incubation was carried
      out either in static or dynamic setting at biomimetic conditions. At 2 weeks, the
      total amount of mineral within the scaffold was quantified using a modified
      Alizarin Red-based assay. Each of the five independent factors was analyzed
      independently and tested for interaction using random effects ANOVA. Statistics
      revealed significant higher order interactions among factors and the combination
      of PDO containing 50% nHA incubated in 1x revised SBF resulted in maximum
      mineralization.

PMID- 19595457
TI  - Functionalizable and ultra stable nanoparticles coated with zwitterionic
      poly(carboxybetaine) in undiluted blood serum.
AB  - A new surface chemistry presenting an abundance of functional groups for ligand
      immobilization in an ultra-low fouling background all in one material for
      nanoparticles was introduced. This surface platform, as demonstrated by
      zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) coated nanoparticles, is
      not only ultra stable in undiluted human blood serum, but also can be conjugated
      to biomolecules conveniently and effectively. Thus, this surface chemistry is
      ideal to create multi-functional nanoparticles for targeted delivery and
      diagnostics. In addition, this work clearly shows that 10% blood serum commonly
      used to evaluate the stability of nanoparticles is insufficient and a new
      evaluation criterion with undiluted blood serum is recommended.

PMID- 19595458
TI  - CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid
      leukemia and myelodysplastic syndromes.
AB  - Methylation is now established as a fundamental regulator of gene transcription.
      To investigate this in haematologic malignancies, we evaluated the aberrant
      promoter methylation of two imprinted genes (MEG3 and SNRPN) in 43 MDS and 42 AML
      patients. MEG3 hypermethylation occurred in 15 MDS patients (34.9%), and in 20
      AML patients (47.6%). SNRPN hypermethylation was observed in 15 MDS patients
      (34.9%), and in 21 AML patients (50%). There were no significant correlations
      between WHO subtype, WPSS score, karyotype, haemoglobin levels, white blood cell
      count, platelet count and CpG methylation of any gene. MEG3 hypermethylation was
      associated with significantly reduced overall survival in individuals with AML
      (HR=1.98, p=0.04), while SNRPN CpG methylation was not associated with survival
      (HR=0.94, p=0.87). In addition, no association between survival and aberrant MEG3
      (HR=2.15, p=0.072) or SNRPN methylation (HR=1.08, p=0.85) was observed in
      patients MDS. Our findings suggest that these genes are abnormally methylated in
      AML and MDS patients, and methylation of MEG3 confers worse overall prognosis.
      The MEG3 methylation status may serve as a useful biomarker in leukemia.

PMID- 19595459
TI  - ER-Golgi network--a future target for anti-cancer therapy.
AB  - Tumor cell demise is an important event in the elimination of abnormal malignant
      cells and provides an important mechanism of natural tumor suppression.
      Abnormalities incapacitating these finely tuned processes provide a strong
      advantage for cancer clones to succeed in evading both the physiological control
      systems and therapeutic intervention. Expanding our knowledge of the molecular
      "crosstalks" that regulate tumor cell demise is crucial in guiding the successful
      design of future anti-cancer therapeutics. Although currently available data
      indicate that elimination of malignant cells often depends on classical apoptotic
      pathways (mitochondrial and/or death-receptor pathways), the evidence is mounting
      that alternative apoptotic and non-apoptotic pathways may effectively contribute
      to tumor cell death. The assumption that every organelle is capable of sensing,
      amplificating and executing cell death is also a relatively novel and unexplored
      concept. As recently shown, the secretory pathway can be actively involved in
      sensing stress stimuli and possibly even initiating and propagating cell death
      signaling. Experimental evidence indicates that ER and Golgi apparatus can
      activate both pro-survival (recovery) mechanisms as well as cell suicide programs
      if the stress-signaling threshold is exceeded. It is thus conceivable that the
      fragile balance of protein trafficking between various subcellular compartments
      provides an exceptional therapeutic opportunity. Interestingly, a growing number
      of reports recognize novel therapeutic targets, including proteins in control of
      endoplasmic reticulum (ER) and Golgi homeostasis. Further studies are, however,
      needed to elucidate precise signaling pathways emanating from ER-Golgi
      compartment. Development of more potent and selective small-molecule drugs that
      activate ER-Golgi mediated cell demise is also needed. As the interest in the
      role of ER-Golgi network during cancer cell death has been gaining momentum, we
      attempt here to critically appraise current status of development of
      investigational anti-cancer agents that target ER and/or Golgi.

PMID- 19595461
TI  - Oxindole-Schiff base copper(II) complexes interactions with human serum albumin:
      spectroscopic, oxidative damage, and computational studies.
AB  - CD and EPR were used to characterize interactions of oxindole-Schiff base
      copper(II) complexes with human serum albumin (HSA). These imine ligands form
      very stable complexes with copper, and can efficiently compete for this metal ion
      towards the specific N-terminal binding site of the protein, consisting of the
      amino acid sequence Asp-Ala-His. Relative stability constants for the
      corresponding complexes were estimated from CD data, using the protein as
      competitive ligand, with values of log K(CuL) in the range 15.7-18.1, very close
      to that of [Cu(HSA)] itself, with log K(CuHSA) 16.2. Some of the complexes are
      also able to interfere in the alpha-helix structure of the protein, while others
      seem not to affect it. EPR spectra corroborate those results, indicating at least
      two different metal species in solution, depending on the imine ligand. Oxidative
      damage to the protein after incubation with these copper(II) complexes,
      particularly in the presence of hydrogen peroxide, was monitored by carbonyl
      groups formation, and was observed to be more severe when conformational features
      of the protein were modified. Complementary EPR spin-trapping data indicated
      significant formation of hydroxyl and carbon centered radicals, consistent with
      an oxidative mechanism. Theoretical calculations at density functional theory
      (DFT) level were employed to evaluate Cu(II)-L binding energies, L-->Cu(II)
      donation, and Cu(II)-->L back-donation, by considering the Schiff bases and the N
      terminal site of HSA as ligands. These results complement previous studies on
      cytotoxicity, nuclease and pro-apoptotic properties of this kind of copper(II)
      complexes, providing additional information about their possibilities of
      transport and disposition in blood plasma.

PMID- 19595460
TI  - Engineering the binding properties of the T cell receptor:peptide:MHC ternary
      complex that governs T cell activity.
AB  - The potency of a T cell is determined in large part by two interactions, binding
      of a cognate peptide to the MHC, and binding of the T cell receptor (TCR) to this
      pepMHC. Various studies have attempted to assess the relative importance of these
      interactions, and to correlate the corresponding binding parameters with the
      level of T cell activity mediated by the peptide. To further examine the
      properties that govern optimal T cell activity, here we engineered both the
      peptide:MHC interaction and the TCR:pepMHC interaction to generate improved T
      cell activity. Using a system involving the 2C TCR and its allogeneic pepMHC
      ligand, QL9-L(d), we show that a peptide substitution of QL9 (F5R), increased the
      affinity and stability of the pep-L(d) complex (e.g. cell surface t(1/2)-values
      of 13 min for QL9-L(d) versus 87 min for F5R-L(d)). However, activity of peptide
      F5R for 2C T cells was not enhanced because the 2C TCR bound with very low
      affinity to F5R-L(d) compared to QL9-L(d) (K(D)=300 microM and K(D)=1.6 microM,
      respectively). To improve the affinity, yeast display of the 2C TCR was used to
      engineer two mutant TCRs that exhibited higher affinity for F5R-L(d) (K(D)=1.2
      and 6.3 microM). T cells that expressed these higher affinity TCRs were
      stimulated by F5R-L(d) in the absence of CD8, and the highest affinity TCR
      exhibited enhanced activity for F5R compared to QL9. The results provide a guide
      to designing the explicit binding parameters that govern optimal T cell
      activities.

PMID- 19595462
TI  - Gene polymorphism at the interleukin 6 -174 G > C locus affects the outcome of
      chronic hepatitis B.

PMID- 19595463
TI  - Mindscape: a convergent perspective on life, mind, consciousness and happiness.
AB  - What are mind, consciousness and happiness, in the fundamental context of life?
      We propose a convergent perspective (coupling evolutionary biology, genomics,
      neurobiology and clinical medicine) that could help us better understand what
      life, mind, consciousness and happiness are, as well as provides empirically
      testable practical implications.

PMID- 19595464
TI  - Implicit and explicit procedural learning in patients recently remitted from
      severe major depression.
AB  - In acute depression a high prevalence of deficits in learning and memory
      performance has been reported. Still, it is unclear whether these cognitive
      deficits are present after remission of clinical symptoms of depression. The
      present study compared 20 inpatients recently remitted from severe major
      depressive disorder (MDD) with 20 healthy matched control participants on two
      sequence learning tasks: a modified serial reaction-time task (SRT) for implicit
      learning, which is sensitive to subcortical and frontal impairments, and a serial
      generation task (SGT) for explicit learning. As compared with performance in
      healthy controls, implicit and explicit learning were not impaired in recently
      remitted inpatients with depression. Intentional acquisition of new information
      was related to the severity of depressive symptoms as patients with higher scores
      on Beck's Depression Inventory (BDI) showed poorer explicit learning. In contrast
      to findings in acute depression, our results suggest a normal degree of learning
      in remitted depression; these findings are consistent with unimpaired fronto
      striatal functioning. However, although not statistically significant, patients
      remitted from melancholic MDD revealed poorer implicit learning performance
      compared with patients remitted from non--melancholic MDD. Longitudinal studies
      in patients with melancholic vs. non-melancholic MDD are needed to investigate
      the course of cognitive functioning during the recovery from MDD.

PMID- 19595465
TI  - Selective antagonism of anticancer drugs for side-effect removal.
AB  - By interfering with signal transduction events that control cell proliferation
      and fate, kinase inhibitors (KIs) hold promise as anticancer agents.
      Nevertheless, the functional role of a kinase depends on the cellular context and
      hence kinase inhibition in off-target cells could lead to side effects. For
      instance, this context dependence renders many KIs potentially cardiotoxic since
      inhibition of primary cancer targets such as ABL, RAF1 or AMPK recruits pro
      apoptotic pathways in cardiomyocytes. Motivated by these observations, we propose
      a mode of 'therapeutic editing' where one drug (the editor) suppresses the side
      effect promoted by the primary drug as it impacts off-target cells. Editor and
      primary drug have overlapping therapeutic impact, and the editor suppresses the
      downstream propagation of toxicity-related signaling.

PMID- 19595466
TI  - BAT: a new target for human obesity?
AB  - Two types of adipose tissue can be distinguished histologically and functionally:
      white (WAT) and brown adipose tissue (BAT). Whereas BAT is specialized in the
      production of heat, WAT stores excess energy as triacylglycerols. BAT is present
      throughout life in rodents, whereas in humans it was thought to involute rapidly
      postnatally, having essentially disappeared within the first years after birth.
      However, positron emission tomography has provided evidence that adults retain
      metabolically active BAT depots that can be induced in response to cold and
      sympathetic nervous system activation. These findings together with the recent
      identification of specific molecular determinants (PRDM16 and BMP7) activating
      brown adipogenesis highlights BAT as a potential relevant target for
      pharmacological and gene expression manipulation to combat human obesity.

PMID- 19595467
TI  - Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus
      Conference (EURECA-CC2).
AB  - BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of
      important European randomized studies were published. In order to help shape
      clinical practice based on best scientific evidence from the literature, the
      International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking
      for an European Consensus' (EURECA-CC2) was organized in Italy under the
      endorsement of European Society of Medical Oncology (ESMO), European Society of
      Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology
      (ESTRO). METHODS: Consensus was achieved using the Delphi method. The document
      was available to all Committee members as a web-based document customized for the
      consensus process. Eight chapters were identified: epidemiology, diagnostics,
      pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality
      of life, follow-up, and research questions. Each chapter was subdivided by a
      topic, and a series of statements were developed. Each member commented and
      voted, sentence by sentence thrice. Sentences upon which an agreement was not
      reached after voting round # 2 were openly debated during a Consensus Conference
      in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting
      system collected the opinions of both the Committee members and the audience
      after each debate. The Executive Committee scored percentage consensus based on
      three categories: "large consensus", "moderate consensus", and "minimum
      consensus". RESULTS: The total number of the voted sentences was 207. Of the 207,
      86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%)
      resulted in minimum consensus. No statement was disagreed by more than 50% of the
      members. All chapters were voted on by at least 75% of the members, and the
      majority was voted on by >85%. CONCLUSIONS: This Consensus Conference represents
      an expertise opinion process that may help shape future programs, investigational
      protocols, and guidelines for staging and treatment of rectal cancer throughout
      Europe.

PMID- 19595468
TI  - No mantle formation in rodent islets -- the prototype of islet revisited.
AB  - Emerging reports on human islets emphasize distinct differences from the widely
      accepted prototype of rodent islets, raising questions over their suitability for
      human studies. Here we aim at elucidating architectural differences and
      similarities of human versus rodent islets. The cellular composition and
      architecture of human and rodent islets were compared through three-dimensional
      (3D) reconstructions. Physiological and pathological changes were examined using
      islets from various mouse models such as non-obese diabetic (NOD), ob/ob, db/db
      mice and during pregnancy. A subpopulation of human islets is composed of
      clusters of alpha-cells within the central beta-cell cores, while the overall
      proportion of alpha-cells varies among islets. In mouse islets under normal
      conditions, alpha-cells are localized in the islet periphery, but they do not
      envelop the entire beta-cell core, so that beta-cells are exposed on the outer
      layer of the islet, as in most human islets. Also, an increased proportion of
      alpha-cells within the central core is observed in the pancreas of mouse models
      exhibiting increased demand for insulin. In summary, human and mouse islets share
      common architectural features as endocrine micro-organs. Since these may hold a
      key to better understanding islet plasticity, our concept of the prototypic islet
      should be revised.

PMID- 19595469
TI  - Resolution of inflammation-related apoptotic processes by the synthetic tellurium
      compound, AS101 following liver injury.
AB  - BACKGROUND/AIMS: Fulminant hepatic failure is a dangerous condition, which occurs
      when large parts of the liver become damaged beyond repair, and the liver is no
      longer able to function. This syndrome is induced by inflammatory processes,
      resulting in acute liver failure. Recently, the organotellurium compound,
      trichloro(dioxoethylene-O,O(')) tellurate (AS101), has been found by our group to
      be able to directly inhibit caspases, due to its Te(IV)-thiol chemistry. The aim
      of this study was to examine the potential of AS101 as an anti-inflammatory and
      anti-apoptotic compound in vitro and in vivo following liver injury. METHODS:
      Propionibacterium acnes-primed LPS-induced liver injury was performed in Balb/c
      mice. ALT/AST, cytokines, caspase-1,-3 and-8 activities, and liver histology were
      assessed. RESULTS: AS101 inhibited TNFalpha or anti-FAS-induced apoptotic
      processes in hepatocytes in vitro. A P. acnes+LPS in vivo liver injury model
      revealed lower serum ALT and AST and reduced necrosis and apoptosis in AS101
      treated mice. IL-18 and IL-1beta reduced levels in AS101-treated mice were
      associated with caspase-1 activity inhibition. Our findings suggest IL-6, IL-17
      and pSTAT3 as additional novel players in the pathogenicity of FHF. Inhibition of
      caspase-3, and-8 activities by AS101 treatment contributed to decreased
      hepatocyte death, resulting in increased survival. CONCLUSIONS: We suggest that
      due to its interaction with key-target cysteine residues, AS101 mediates anti
      inflammatory and anti-apoptotic effects in this FHF model, which may serve as a
      potent treatment for mitigation of hepatic damage.

PMID- 19595470
TI  - New molecular insights into the mechanisms of cholestasis.
AB  - Recent progress in basic research has enhanced our understanding of the molecular
      mechanisms of normal bile secretion and their alterations in cholestasis. Genetic
      transporter variants contribute to an entire spectrum of cholestatic liver
      diseases and can cause hereditary cholestatic syndromes or determine
      susceptibility and disease progression in acquired cholestatic disorders.
      Cholestasis is associated with complex transcriptional and post-transcriptional
      alterations of hepatobiliary transporters and enzymes participating in bile
      formation. Ligand-activated nuclear receptors for bile acids and other biliary
      compounds play a key role in the regulation of genes required for bile formation.
      Pharmacological interventions in cholestasis may aim at modulating such novel
      regulatory pathways. This review will summarize the principles of molecular
      alterations in cholestasis and will give an overview of potential clinical
      implications.

PMID- 19595471
TI  - Combining transbronchial biopsy using endobronchial ultrasonography with a guide
      sheath and positron emission tomography for the diagnosis of small peripheral
      pulmonary lesions.
AB  - To evaluate the combination of transbronchial biopsy (TBB) using endobronchial
      ultrasonography with a guide sheath (EBUS-GS) and positron emission tomography
      with fluorodeoxyglucose (FDG-PET) for the diagnosis of small peripheral pulmonary
      lesions (PPLs) < or = 30 mm in mean diameter. A total of 74 PPLs (69.2%) were
      diagnosed by TBB using EBUS-GS with X-ray fluoroscopy. Diagnostic yield by FDG
      PET was 78.5% for the 107 PPLs examined. Diagnostic yield with the combination of
      TBB using EBUS-GS and FDG-PET (90.7%) was significantly higher compared with that
      for each procedure alone. A significant increment in diagnostic yield with this
      combination was seen for PPLs >20mm and < or = 30 mm and for malignant lesions.
      Combination of TBB using EBUS-GS and FDG-PET is useful for the diagnosis of small
      PPLs.

PMID- 19595474
TI  - Assisted migration: part of an integrated conservation strategy.

PMID- 19595472
TI  - Restoration of leukotriene B(4)-12-hydroxydehydrogenase/15- oxo-prostaglandin 13
      reductase (LTBDH/PGR) expression inhibits lung cancer growth in vitro and in
      vivo.
AB  - Leukotriene B(4)-12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase
      (LTBDH/PGR) is a bifunctional enzyme capable of inactivating leukotriene B(4)
      (LTB(4)) and 15-oxo-prostaglandins (15-PGs). Its role in growth suppressive
      functions in lung cancer was studied in in vitro and in vivo systems. The
      LTBDH/PGR gene was expressed in lung cancer cell lines through recombinant
      adenovirus infection, and through a tetracycline-inducible expression system.
      After restoration of LTBDH/PGR expression in LTBDH/PGR-negative (H1299) or -low
      (A549) lung cancer cell lines, the restored enzyme induced apoptosis and growth
      inhibition in vitro. Ectopic expression of LTBDH/PGR caused also suppression of
      tumorigenicity of A549 cells in nude mice. In contrast, LTBDH/PGR over-expression
      in LTBDH/PGR-positive (H157) lung cancer cell line induced little apoptosis and
      growth inhibition. This study indicates that restoration of LTBDH/PGR expression
      is effective in preventing lung cancer growth in vitro and in vivo.

PMID- 19595475
TI  - Assisted colonization: evaluating contrasting management actions (and values) in
      the face of uncertainty.

PMID- 19595476
TI  - Emerging horizons in biodiversity and ecosystem functioning research.
AB  - Two decades of intensive research have provided compelling evidence for a link
      between biodiversity and ecosystem functioning (B-EF). Whereas early B-EF
      research concentrated on species richness and single processes, recent studies
      have investigated different measures of both biodiversity and ecosystem
      functioning, such as functional diversity and joint metrics of multiple
      processes. There is also a shift from viewing assemblages in terms of their
      contribution to particular processes toward placing them within a wider food web
      context. We review how the responses and predictors in B-EF experiments are
      quantified and how biodiversity effects are shaped by multitrophic interactions.
      Further, we discuss how B-EF metrics and food web relations could be addressed
      simultaneously. We conclude that addressing traits, multiple processes and food
      web interactions is needed to capture the mechanisms that underlie B-EF relations
      in natural assemblages.

PMID- 19595477
TI  - The precautionary principle in managed relocation is misguided advice.

PMID- 19595478
TI  - A NAC transcription factor gene of Chickpea (Cicer arietinum), CarNAC3, is
      involved in drought stress response and various developmental processes.
AB  - NAC transcription factors have been found to play important roles in plant
      development and responses to environmental stresses. Based on two cDNA libraries
      constructed from the PEG-treated and -nontreated seedling leaves of chickpea, a
      NAC gene, CarNAC3, was isolated and characterized. The results indicated that
      CarNAC3 contained 285 amino acids and had a conserved NAC domain. It was
      localized in the nucleus and possessed trans-activation activity in the C
      terminus. Phylogenetic analysis showed that CarNAC3 belonged to the NAP (NAC
      like, activated by APETALA3/PISTILLATA) subgroup of the NAC protein family.
      CarNAC3 exhibited organ-specific expression and its induction was strongly
      dependent on leaf age. CarNAC3 showed differential expression patterns during
      seed development and germination, and could be significantly induced by drought
      stress, abscisic acid (ABA), ethephon (Et) and indole-3-acetic acid (IAA), but
      was inhibited by N-6-benzyl-adenine (6-BA). Our data suggest that CarNAC3 may be
      a transcriptional activator involved in drought stress response and various
      developmental processes.

PMID- 19595480
TI  - Survey of meticillin-resistant Staphylococcus aureus policies in UK eye
      departments.
AB  - The purpose of this study was to investigate meticillin-resistant Staphylococcus
      aureus (MRSA) screening and decolonisation practices for patients undergoing
      routine cataract surgery in ophthalmology departments across the UK. A postal
      questionnaire survey of all ophthalmology departments in the UK was carried out,
      with 75 of 152 (49.3%) questionnaires returned. Sixty-three percent of units had
      a departmental MRSA policy. Preoperative MRSA screening was performed in 50
      (66.7%) units, three of which screened all preoperative patients and the
      remainder performed selective screening. The proportion of patients screened for
      MRSA ranged from 0 to 100%, with a median of 2% and a mean of 9.9% (95%
      confidence interval: 3.5-16.2%). Overall, 65.3% of respondents felt that their
      departmental policy was reasonable, although there was considerable
      dissatisfaction and confusion, with comments identifying lack of evidence and the
      need for guidelines applicable to day-case cataract surgery. The survey
      demonstrates significant inconsistencies in preoperative MRSA screening practice
      in ophthalmology departments throughout the UK. Current recommendations from the
      Department of Health suggest that day-case ophthalmology patients do not require
      routine screening, although the implication appears that high risk patients
      continue to do so. Further investigation is required to ascertain the scientific
      validity of these recommendations.

PMID- 19595479
TI  - Prevalence of adult atopic dermatitis among nursing staff in a Taiwanese medical
      center: a pilot study on validation of diagnostic questionnaires.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous
      studies have focused mostly on pediatric patients, and investigations emphasizing
      adult AD have been limited. OBJECTIVE: We set out to determine the 1-year
      prevalence and evaluate the validity of the International Study of Asthma and
      Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD
      questionnaires of adult AD in Taiwan. METHODS: We conducted a cross-sectional
      study among nursing staff at a university hospital. The 1-year prevalence of AD
      was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists'
      diagnosis based on Hanifin and Rajka criteria was used as a reference for
      validation. RESULTS: The overall response rate was 92.9%, equivalent to 1131
      complete questionnaires. Ninety adult patients with AD (8%) were identified by
      dermatologists' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and
      specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%)
      patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively.
      Using the receiver operating characteristic curve analysis, the UKWP criteria
      performed significantly better than its ISAAC counterpart. Further analysis
      indicated that modification of these criteria resulted in significant improvement
      in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and
      55.2% sensitivity and specificity, respectively, whereas modified UKWP
      demonstrated 82.2% and 94.2% sensitivity and specificity, respectively.
      LIMITATION: Most of the study subjects were female with a high educational
      background. CONCLUSION: Currently available questionnaire instruments do not
      perform well in the identification of adult patients with AD. Modification of the
      original questionnaires may allow for future large-scale epidemiologic studies.

PMID- 19595481
TI  - Experimental evaluation of the efficacy of sanitation procedures in operating
      rooms.
AB  - BACKGROUND: There remains much debate on how to define an adequate sanitation
      protocol in hospital environments. METHODS: The efficacy of a sanitation protocol
      in the operating room (OR) of a modern hospital was evaluated by measuring
      bacterial load on different types of finishing materials of all internal surfaces
      (ie, walls, floors, and furnishings). Samples were obtained before cleaning and
      over the subsequent 24 hours. A total of 2124 microbiological samples were
      collected using RODAC plates and sterile swabs. RESULTS: The data demonstrate a
      very significant postsanitation reduction of bacterial load on floors and
      furnishings; however, no significant data on walls were obtained, because of the
      low levels of initial contamination (1.50 to 5.98 cfu/100 cm2). The increase in
      postsanitation bacterial load over time was greater on smooth materials than on
      porous materials, on which a further reduction in contamination was seen. The
      study outcomes were confirmed by simulation experiments in which different
      materials were contaminated with a predetermined bacterial load and then
      subjected to the sanitation protocol. These simulation experiments were carried
      out both in vitro and in an eddy-flux testing room that simulated a full-scale OR
      similar (in terms of architectonic systems) to a real setting. CONCLUSION: Our
      data demonstrate that the spatial (vertical/horizontal) disposition of materials
      affects the initial contamination level, which is always much lower on vertical
      surfaces than on horizontal ones. Moreover, postsanitation bacterial load
      recovery is dependent on the physical properties of the surface.

PMID- 19595482
TI  - [Blood coagulation factor levels in candidates for liver transplantation:
      correlation with disease severity].
AB  - OBJECTIVE: To correlate blood coagulation factor levels with disease severity in
      cirrhotic patients evaluated as candidates for liver transplantation. MATERIAL
      AND METHOD: We included 87 patients (75.9% men) with a mean age of 54+/-9.4
      years. Etiology and Child-Turcotte-Pugh (CTP) class were as follows: alcohol
      related (36.8%), hepatitis C virus infection (35.6%), hepatitis B virus infection
      (11.5%) and other (16.1%); class A (13.8%), class B (40.2%) and class C (46%),
      respectively. The mean value of the Model for End-Stage Liver Disease (MELD)
      score was 14.5+/-5.9. Levels of factors II, V, VII, VIII, IX and X were compared
      between each CTP grade and with the MELD score. RESULTS: Except for factor VIII,
      all the clotting factors were reduced in our series (in particular factors II, V
      and VII) and deficiencies in these factors were closely related to CTP grade with
      statistical significance for stage C (p <0.05). We also found a marked inverse
      correlation between the MELD score and factors II, V, VII, IX and X values (p
      <0.05). CONCLUSIONS: A correlation was found between reduced levels of factors
      II, V, VII, IX and X in liver cirrhosis and the severity of liver disease.

PMID- 19595483
TI  - [Evaluation of preferences in patients with gastroesophageal reflux disease and
      dysphagia concerning treatment with lansoprazole orally disintegrating tablets].
AB  - INTRODUCTION AND OBJECTIVE: Recently, a new lansoprazole formulation consisting
      of orally disintegrating tablets has become available, which could improve
      acceptability and compliance with this type of medication. The aim of the present
      study was to evaluate preferences in patients with gastroesophageal reflux
      disease concerning lansoprazole orally disintegrating tablets compared with
      lansoprazole capsules. MATERIAL AND METHODS: A phase IV, multicenter, crossed,
      open and randomized clinical trial was performed in patients with symptoms of
      gastroesophageal reflux disease and associated dysphagia. The patients were
      treated with 30mg lansoprazole capsules for 3 days and with 30mg lansoprazole
      orally disintegrating tablets for another 3 days. The order of treatment (first
      capsules followed by orally disintegrating tablets or vice versa) was determined
      by centralized block randomization. The main measure was the visual analog scale
      (VAS) score in which patients was asked to rate their degree of preference for
      the orally disintegrating tablets or the capsules. RESULTS: Of the 145 patients
      included, 126 could be evaluated by the protocol. A total of 47% (59/126) of the
      patients preferred the orally disintegrating tablets, 33% (42/126) preferred the
      capsules and the remainder (25/126) had no preference. The mean preference value
      in the VAS was 5.31 (4.72 +/- 5.90) in favor of the orally disintegrating
      tablets, although this difference was not statistically significant. In general,
      differences in favor of the orally disintegrating tables were more marked in
      older patients. The percentage of patients free of pyrosis at the end of both
      treatment sequences was approximately 75% with no differences according to which
      treatment was administered first. Finally, preference evaluation through
      willingness to pay techniques showed similar results, again in favor of the
      orally disintegrating tablets (4.18 euro +/- 6.86 euro vs 3.47 euro +/- 5.78
      euro). CONCLUSION: The acceptability of pharmaceutical formulations of
      lansoprazole in capsules and orally disintegrating tables is similar among
      patients with gastroesophageal reflux disease and associated dysphagia. However,
      a clear, but nonsignificant, trend was observed in favor of orally disintegrating
      tablets among older patients.

PMID- 19595484
TI  - [Treatment of a type I carcinoid gastric tumor through endoscopic mucosal
      resection using a cap].

PMID- 19595485
TI  - [Predictors of cognitive decline in the elderly].
AB  - The elderly population is currently increasing. In this population there is a
      high incidence of cognitive decline and dementia, which has a negative influence
      on personal life and family functioning, as well as economic and healthcare
      repercussions. The present article aims to indicate possible predictors of
      cognitive decline with a view to predicting this situation and intervening before
      the cognitive impairment is unavoidable. Some predictors of cognitive impairment
      could be the following: age, sex, education, a family history of dementia,
      objective and subjective difficulties with memory, several medical problems
      (hypertension and diabetes), sensory-motor difficulties, hypometabolism in some
      cerebral areas, reduced hippocampal size, carrying one or two apolipoprotein e4
      alleles, a low score in cognitive tasks (especially immediate and delayed
      recall), deficits in associative learning and naming, low cognitive plasticity,
      depression, a low literacy level, poor general cognitive functioning, low
      participation in social activities, low physical activity, lack of social
      support, the use of medication and, finally, sleep-related problems. All of these
      factors could be important in predicting cognitive decline in very old age.

PMID- 19595486
TI  - [Stroke in the very old].

PMID- 19595487
TI  - [Use of combined treatment with melatonin and clomethiazole in circadian rhythm
      sleep disorder in the elderly with dementia].

PMID- 19595488
TI  - 1,5-Diaryl-2-ethyl pyrrole derivatives as antimycobacterial agents: design,
      synthesis, and microbiological evaluation.
AB  - During the search of novel antitubercular drugs related to BM 212, new
      diarylpyrroles were designed and synthesized on the basis of a structure-activity
      relationship analysis of many pyrroles previously described by us. Among them, 1
      (4-fluorophenyl)-2-ethyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H
      pyrrole (2b) proved to be particularly active, with a minimum inhibitory
      concentration (MIC, expressed as microg/mL) and a protection index (PI) better
      than or comparable to those of reference compounds. Also the remaining compounds
      were very active, although their MIC and PI were in general lower than those of
      their parent 2-methyl analogues.

PMID- 19595489
TI  - Unsaturated dideoxy fluoro-ketopyranosyl nucleosides as new cytostatic agents: a
      convenient synthesis of 2,6-dideoxy-3-fluoro-4-keto-beta-D-glucopyranosyl
      analogues of uracil, 5-fluorouracil, thymine, N4-benzoyl cytosine and N6-benzoyl
      adenine.
AB  - The beta-protected nucleosides of uracil (2a), 5-fluorouracil (2b), thymine (2c),
      N(4)-benzoyl cytosine (2d) and N(6)-benzoyl adenine (2e) were synthesized by
      condensation of the peracetylated 3-deoxy-3-fluoro-D-glucopyranose (1) with the
      corresponding silylated bases. The nucleosides were deacetylated and several
      subsequent protection and deprotection steps afforded the partially acetylated
      analogues 6a-e. Selective iodination followed by hydrogenation gave the
      acetylated dideoxy analogues of uracil (8a), 5-fluorouracil (8b), thymine (8c),
      N(4)-benzoyl cytosine (8d) and N(6)-benzoyl adenine (8e), respectively. Finally,
      direct oxidation of the free hydroxyl group at the 4'-position of 8a-e, and
      simultaneous elimination reaction of the beta-acetoxyl group, afforded the
      desired unsaturated 2,6-dideoxy-3-fluoro-4-keto-beta-D-glucopyranosyl derivatives
      9a-e. The new analogues were evaluated for antiviral and cytostatic activity.
      Compounds 9a-e were not active against a broad panel of DNA and RNA viruses at
      subtoxic concentrations. However, they were markedly cytostatic against a variety
      of tumor cell lines. The compounds should be regarded as potential new lead
      compounds to be further investigated for anticancer therapy.

PMID- 19595490
TI  - [The concept of aspirin "resistance": mechanisms and clinical relevance].
AB  - Aspirin, a 110-year-old molecule, is a cornerstone in the treatment of
      atherothrombotic patients. The concept of aspirin "resistance" emerged
      approximately 15 years ago and is of growing interest. Aspirin resistance,
      defined as a lack of inhibition of cyclo-oxygenase-1 (COX-1), is a rare
      phenomenon and its clinical relevance can hardly be studied. On the contrary,
      residual platelet hyperactivity is more common and affects 20 to 30% of aspirin
      treated patients. This latter phenomenon corresponds to sustained platelet
      reactivity despite a proper inhibition of COX-1 by aspirin. Several meta-analyses
      suggest that residual platelet hyperactivity could be a risk factor for the
      recurrence of ischemic events in aspirin-treated patients. Causes of biological
      non-responsiveness to aspirin are discussed, including the role of compliance,
      drug-drug interactions, genetic polymorphisms and diabetes mellitus. Ongoing
      studies are designed to find out the mechanisms of residual platelet
      hyperactivity, determine its potential clinical relevance and delineate the more
      appropriate assays in order to identify patients who may benefit of a tailored
      antiplatelet therapy.

PMID- 19595491
TI  - Fate of linear alkylbenzenes and benzothiazoles of anthropogenic origin and their
      potential as environmental molecular markers in the Pearl River Delta, South
      China.
AB  - The mass emissions of linear alkylbenzenes (LABs), benzothiazole (BT), and 2-[4
      morpholinyl]benzothiazole (24MoBT) from anthropogenic activities within one year
      were estimated according to the population and the number of automobiles in the
      Pearl River Delta (PRD), South China. Based on the estimation, the distribution
      of these compounds among various environmental media was simulated with a mass
      balance box model established in the present study. The results showed that 79%
      of LABs generated in the PRD was stored in sediment while only 1.3% of LABs was
      presumably transported to the adjacent South China Sea (SCS). On the contrary,
      47% of BT and 77% of 24MoBT generated in the region were carried with riverine
      runoff to the coastal ocean. The results from the present study suggest that
      hydrophobic compounds tend to stay in the watershed of the PRD, whereas
      hydrophilic ones mainly outflow to the coastal ocean.

PMID- 19595492
TI  - Association between attendance at religious services and self-reported health in
      22 European countries.
AB  - There are consistent reports of protective associations between attendance at
      religious services and better self-rated health but existing data rarely consider
      the social or individual context of religious behaviour. This paper investigates
      whether attendance at religious services is associated with better self-rated
      health in diverse countries across Europe. It also explores whether the
      association varies with either individual-level (gender, educational, social
      contact) or country-level characteristics (overall level of religious practice,
      corruption, GDP). Cross-sectional data from round 2 of the European Social Survey
      were used and 18,328 men and 21,373 women from 22 European countries were
      included in multilevel analyses, with country as higher level. Compared to men
      who attended religious services at least once a week, men who never attended were
      almost twice as likely to describe their health as poor, with an age and
      education adjusted odds ratio of 1.83 [95% CI, 1.49-2.26]. A similar but weaker
      effect was seen in women, with an age and education adjusted odds ratio of 1.38
      [1.19-1.61]. The associations were reduced only marginally in men by controlling
      for health status, social contact and country-level variables, but weakened in
      women. The relationships were stronger in people with longstanding illness, less
      than university education and in more affluent countries with lower levels of
      corruption and higher levels of religious belief. These analyses confirm that an
      association between less frequent attendance at religious services and poor
      health exists across Europe, but emphasise the importance of taking individual
      and contextual factors into account. It remains unclear to what extent the
      observed associations reflect reverse causality or are due to differing
      perceptions of health.

PMID- 19595493
TI  - Growth of white matter in the adolescent brain: myelin or axon?
AB  - White matter occupies almost half of the human brain. It contains axons
      connecting spatially segregated modules and, as such, it is essential for the
      smooth flow of information in functional networks. Structural maturation of white
      matter continues during adolescence, as reflected in age-related changes in its
      volume, as well as in its microstructure. Here I review recent observations
      obtained with magnetic resonance imaging in typically developing adolescents and
      point out some of the known variations in structural properties of white matter
      vis-a-vis brain function in health and disease. I conclude by re-focusing the
      interpretations of MR-based studies of white matter from myelin to axon.

PMID- 19595494
TI  - [Chronic obstructive pulmonary disease and heart failure].
AB  - Chronic obstructive pulmonary disease (COPD) is commonly associated with heart
      failure. Individuals with COPD have a 4.5-fold greater risk of developing heart
      failure than those without. The sensitivity and specificity of clinical judgment
      in the diagnosis of heart failure in patients with COPD can be enhanced by
      biological markers such as B-type natriuretic peptide and N-terminal pro-B-type
      natriuretic peptide. Correct interpretation of imaging results (mainly
      echocardiographic findings) and lung function tests can also help establish the
      co-occurrence of both conditions. There is little evidence on the management of
      patients with COPD and heart failure, although treatment of COPD undeniably
      affects the clinical course of patients with heart failure and viceversa.

PMID- 19595495
TI  - Potential agents to control enamel caries-like lesions.
AB  - OBJECTIVES: To assess whether pastes containing casein phosphopeptide-amorphous
      calcium phosphate (CPP-ACP) and calcium sodium phosphosilicate (CSP) control
      artificial caries lesion progression. METHODS: Enamel slabs of bovine teeth were
      embedded in polyester resin and had their enamel surfaces serially polished, and
      tested for surface microhardness (SMH, 25 g, 5 s). Incipient caries-like lesions
      were pre-formed and specimens were evaluated by microhardness test (SMH(post
      lesion)) and randomly assigned to five treatment groups (n=15): (1) regular
      dentifrice (RE, 1,100 ppm F); (2) dentifrice with calcium sodium phosphosilicate
      (CSP); (3) amorphous calcium phosphate stabilized by casein phosphopeptide (CPP
      ACP); (4) CPP-ACP with 900 ppm F (CPP-ACP+F) and (5) control group-unexposed to
      any remineralizing agent. Treatments were applied five times, after the de
      remineralization period in the cariogenic challenges. Post-treatments SMH
      measurements were conducted (SMH(post-treatment)). RESULTS: ANOVA was applied for
      data evaluation and revealed a significant difference among the treatments
      (p=0.0161). Tukey's test was conducted and the percentage of mineral loss was
      calculated. Specimens exposed to CSP (7.1%), RE (6.7%) and CPP-ACP+F (3.8%)
      showed lower mineral loss than those that in the control group (-11.0%). CPP-ACP
      group (3.2%) differed from the control, CSP and RE groups. CONCLUSIONS: Depending
      on the agent used, a remineralizing effect may be expected, which reflects in
      caries lesions progression.

PMID- 19595496
TI  - No difference in autopsy detected injuries in cardiac arrest patients treated
      with manual chest compressions compared with mechanical compressions with the
      LUCAS device--a pilot study.
AB  - AIM: To compare the variety and incidence of internal injuries after manual and
      mechanical chest compressions during CPR. METHODS: In a prospective pilot study
      conducted in two Swedish cities, 85 patients underwent autopsy after unsuccessful
      resuscitation attempts with manual or mechanical chest compressions, the latter
      with the LUCAS device. Autopsy was performed and the results were evaluated
      according to a specified protocol. RESULTS: No injuries were found in 26/47
      patients in the manual group and in 16/38 patients in the LUCAS group (p=0.28).
      Sternal fracture was present in 10/47 in the manual group and 11/38 in the LUCAS
      group (p=0.46), and there were multiple rib fractures (> or =3 fractures) in
      13/47 in the manual group and in 17/38 in the LUCAS group (p=0.12). Bleeding in
      the ventral mediastinum was noted in 2/47 and 3/38 in the manual and LUCAS groups
      respectively (p=0.65), retrosternal bleeding in 1/47 and 3/38 (p=0.32),
      epicardial bleeding in 1/47 and 4/38 (p=0.17), and haemopericardium in 4/47 and
      3/38 (p=1.0) respectively. One patient in the LUCAS group had a small rift in the
      liver and one patient in the manual group had a rift in the spleen. These
      injuries were not considered to have contributed to the patient's death.
      CONCLUSION: Mechanical chest compressions with the LUCAS device appear to be
      associated with the same variety and incidence of injuries as manual chest
      compressions.

PMID- 19595497
TI  - Family history of uterine fibroids associated with low level of fumarate
      hydratase in leiomyomata cells.

PMID- 19595498
TI  - Equivocating on the polluter-pays principle: The consequences for Pakistan.
AB  - The polluter-pays principle has been widely implemented in OECD countries and
      credited for bring about a significant reduction in pollutant discharge. However,
      it has had only limited implementation in developing countries. The consequences
      of not implementing it in developing countries, to the extent they are
      documented, are limited to estimating the economic damages of environmental
      degradation. Yet there are several other but seldom documented negative
      consequences of the failure to implement the polluter-pays principle. These
      consequences are documented in the case of Pakistan. They include limited
      construction of effluent treatment plants, heavy dependence on the government and
      international donors for funding the only two operational common effluent
      treatment plants, significant operational issues at the two common effluent
      treatment plants, missed opportunities to build cost-effective common effluent
      treatment plants and minimal environmental improvements from isolated investments
      in individual effluent treatment plants in addition to the already documented
      significant level of environmental degradation due to uncontrolled pollutant
      discharge.

PMID- 19595499
TI  - Does an energy efficiency label alter consumers' purchasing decisions? A latent
      class approach based on a stated choice experiment in Shanghai.
AB  - In this paper we conducted a hypothetical choice experiment in Shanghai, China,
      to examine whether the China Energy Efficiency Label influences consumers'
      choices of air conditioners and refrigerators. A latent class approach was
      applied to observe both heterogeneities among the respondents and product brands.
      Our results suggested that consumers in Shanghai were well aware of the China
      Energy Efficiency Label and tended to pay more attention to products with such
      labels. In addition, air conditioners and refrigerators affixed with a
      hypothetical label that indicates saving in electricity bills compared with a
      standard model received significant preferences, which suggested that the more
      information manufacturers provide, the more their products would be preferred by
      consumers. Finally, weighted by class probability, the willingness to pay values
      for more energy efficient refrigerators were higher than those for more energy
      efficient air conditioners, implying that Shanghai consumers have greater
      incentive to pay more for appliances they use more frequently.

PMID- 19595500
TI  - Reassessing the current UICC/AJCC TNM staging for renal cell carcinoma.
AB  - CONTEXT: The outcome prediction for renal cell cancer (RCC) remains
      controversial, and although many parameters have been tested for prognostic
      significance, only a few have achieved widespread acceptance in clinical
      practice. The TNM staging system defines local extension of the primary tumour
      (T), involvement of regional lymph nodes (N), and presence of distant metastases
      (M). OBJECTIVE: This review focuses on reassessing the current TNM staging system
      for RCC. EVIDENCE ACQUISITION: A literature search in English was performed using
      the National Library of Medicine database and the following keywords: renal cell
      cancer, kidney neoplasm, and staging. We scrutinized 1952 references, and 62 were
      selected for review based on their pertinence, study size, and overall
      contribution to the field. EVIDENCE SYNTHESIS: The prognostic significance of
      tumour size for localized RCC has been investigated in a large number of studies.
      As a consequence, many modifications of the TNM staging system were primarily
      made to the size cut points between stage I and II tumours. The latest three
      revisions of the TNM system are systematically reviewed. For the heterogeneous
      group of locally advanced RCCs, involving different anatomic structures
      surrounding the kidney, the situation is still the subject of controversial
      scientific dispute. In detail, perirenal fat invasion, direct infiltration of the
      ipsilateral adrenal gland, invasion of the urinary collecting system,
      infiltration of renal sinus fat, and vena cava and renal vein thrombosis are
      disputed. Finally, staging of lymph node metastases and distant metastatic
      disease is discussed. CONCLUSIONS: Special emphasis should be put on renal sinus
      invasion for stage evaluation. Retrospective studies relying on material
      collected at a time when no emphasis was placed on adequate sampling of the renal
      sinus should be treated with caution. In view of new treatment opportunities, the
      current TNM staging system of RCC and any other staging system must be dynamic.

PMID- 19595501
TI  - Bipolar versus monopolar transurethral resection of the prostate: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - CONTEXT: Incorporation of bipolar technology in transurethral resection (TUR) of
      the prostate (TURP) potentially offers advantages over monopolar TURP (M-TURP).
      OBJECTIVE: To evaluate the evidence by a meta-analysis, based on randomized
      controlled trials (RCTs) comparing bipolar TURP (B-TURP) with M-TURP for benign
      prostatic obstruction. Primary end points included efficacy (maximum flow rate
      [Q(max)], International Prostate Symptom Score) and safety (adverse events).
      Secondary end points included operation time and duration of irrigation,
      catheterization, and hospitalization. EVIDENCE ACQUISITION: Based on a detailed,
      unrestricted strategy, the literature was searched up to February 19, 2009, using
      Medline, Embase, Science Citation Index, and the Cochrane Library to detect all
      relevant RCTs. Methodological quality assessment of the trials was based on the
      Dutch Cochrane Collaboration checklist. Meta-analysis was performed using Review
      Manager 5.0. EVIDENCE SYNTHESIS: Sixteen RCTs (1406 patients) were included.
      Overall trial quality was low (eg, allocation concealment and blinding of outcome
      assessors were poorly reported). No clinically relevant differences in short-term
      (12-mo) efficacy were detected (Q(max): weighted mean difference [WMD]: 0.72
      ml/s; 95% confidence interval [CI], 0.08-1.35; p=0.03). Data on follow-up of >12
      mo are scarce for B-TURP, precluding long-term efficacy evaluation. Treating 50
      patients (95% CI, 33-111) and 20 patients (95% CI, 10-100) with B-TURP results in
      one fewer case of TUR syndrome (risk difference [RD]: 2.0%; 95% CI, 0.9-3.0%;
      p=0.01) and one fewer case of clot retention (RD: 5.0%; 95% CI, 1.0-10%; p=0.03),
      respectively. Operation times, transfusion rates, retention rates after catheter
      removal, and urethral complications did not differ significantly. Irrigation and
      catheterization duration was significantly longer with M-TURP (WMD: 8.75 h; 95%
      CI, 6.8-10.7 and WMD: 21.77 h; 95% CI, 19.22-24.32; p<0.00001, respectively).
      Inferences for hospitalization duration could not be made. PlasmaKinetic TURP
      showed an improved safety profile. Data on TUR in saline (TURis) are not yet
      mature to permit safe conclusions. CONCLUSIONS: No clinically relevant
      differences in short-term efficacy exist between the two techniques, but B-TURP
      is preferable due to a more favorable safety profile (lower TUR syndrome and clot
      retention rates) and shorter irrigation and catheterization duration. Well
      designed multicentric/international RCTs with long-term follow-up and cost
      analysis are still needed.

PMID- 19595502
TI  - Awareness within the French population concerning stroke signs, symptoms, and
      risk factors.
AB  - BACKGROUND: Effective implementation of early treatment strategies for stroke
      requires prompt admission to hospital which could be delayed for several reasons
      such as poor awareness of population. OBJECTIVE: To assess current public
      knowledge of stroke. METHODS: We randomly selected 411 persons living in Poitou
      Charentes (area of nearly 1,700,000 persons in France) and performed an open
      ended questionnaire regarding stroke risk factors, stroke warning signs, source
      of information, and stroke attitude. RESULTS: Most of the patients (62.3%) were
      able to name three risk factors but not to report the most important and less
      than half of the respondents were able to recognize one or more stroke warning
      sign. Predictors of adequate knowledge of both stroke risk factors and warning
      signs were similar and included age and sources of information (books, magazines
      and newspapers or family members or relatives who have suffered from a stroke or
      general practitioner). CONCLUSIONS: This study emphasizes that knowledge of
      stroke risk factors and warning signs was moderate at best. Improvements can only
      result from using a broad range of sustained educational efforts through simple
      and understandable school education or public media.

PMID- 19595503
TI  - Surgical strategies using cerebral revascularization in complex middle cerebral
      artery aneurysms.
AB  - OBJECTIVES: To describe surgical strategies using cerebral revascularization for
      complex middle cerebral artery aneurysms unsuitable to microsurgical clipping.
      MATERIALS AND METHODS: In this study, the clinical features, case management, and
      results in 9 consecutive patients who underwent 10 cerebral revascularization
      procedures between January 1999 and April 2008 were retrospectively analyzed. The
      patient population consisted of 6 men and 3 women whose ages ranged from 15 to 71
      years (mean, 42.4 years). The size of the aneurysms ranged from 12 to 35 mm
      (mean, 24.3 mm). Treated aneurysms were located in the M1 segment in 2 patients,
      the middle cerebral artery (MCA) bifurcation in 3 patients, the distal M3 segment
      in 3 patients, and the anterior temporal artery (ATA; the early cortical branch
      of the M1 segment) in 1 patient. A total of 10 revascularizations were performed.
      Three aneurysms were saccular and six aneurysms were fusiform. For the fusiform
      aneurysms of the M1 segment in 2 patients, superficial temporal artery (STA)
      trunk-saphenous vein (SV)-MCA bypasses followed by trapping were performed. For
      the large saccular MCA bifurcation aneurysms in 3 patients, STA-MCA bypasses
      followed by complete neck clipping, including the revascularized branch with the
      preservation of the flow of the other branch, were performed in 2 cases, and a
      STA trunk-SV-MCA bypass secondary to direct neck clipping with the preservation
      of both M2 branches was performed in 1 case. For the fusiform distal MCA
      aneurysms, STA-MCA bypasses in 2 patients and in situ MCA-MCA bypasses in 2
      patients were performed. In one case involving distal MCA fusiform aneurysm, STA
      MCA bypass and MCA-MCA bypass were performed simultaneously. In a case involving
      fusiform ATA aneurysm, primary reanastomosis after aneurysm excision was
      performed in 1 patient. RESULTS: The post-operative 3-month Glasgow outcome
      scales were good recovery in 6 patients, severe disability in 1 patient, a
      vegetative state in 1 patient, and death in 1 patient. A follow-up angiography
      was performed in 6 patients and revealed a patent bypass in 5 patients. In one
      case treated by direct neck clipping secondary to cerebral revascularization, the
      angiography obtained 2 weeks later showed graft occlusion, but there were no
      neurologic symptoms. Among the unfavorable outcomes of 3 patients who did not
      undergo follow-up angiography, surgery-related morbidity secondary to cerebral
      infarction was due to the size discrepancy between the donor and recipient
      vessels in 1 patient with severe disability. In the other 2 patients, the
      preoperative conditions were Hunt and Hess grade V. CONCLUSIONS: Cerebral
      revascularization is a safe and effective technique of treatment for selective
      cases of complex large or giant aneurysms and unclippable fusiform aneurysms in
      the MCA.

PMID- 19595504
TI  - Comparison of soil pollution concentrations determined using AAS and portable XRF
      techniques.
AB  - Past mining activities in the area of Silvermines, Ireland, have resulted in
      heavily polluted soils. The possibility of spreading pollution to the surrounding
      areas through dust blow-offs poses a potential threat for the local communities.
      Conventional environmental soil and dust analysis techniques are very slow and
      laborious and consequently there is a need for fast and accurate analytical
      methods, which can provide real-time in situ pollution mapping. Laboratory-based
      aqua regia acid digestion of the soil samples collected in the area followed by
      the atomic absorption spectrophotometry (AAS) analysis confirmed very high
      pollution, especially by Pb, As, Cu, and Zn. In parallel, samples were analyzed
      using portable X-ray fluorescence radioisotope and miniature tube powered (XRF)
      NITON instruments and their performance was compared. Overall, the portable XRF
      instrument gave excellent correlation with the laboratory-based reference AAS
      method.

PMID- 19595506
TI  - Preparation, characterization and photocatalytic properties of ZnTiO3 powders.
AB  - A novel photocatalyst ZnTiO(3) powder was prepared by a modified alcoholysis
      method, using ethylene glycol as reagent/solvent and acetylacetone as stabilizer.
      A series of analytical techniques were used to characterize the crystallinity,
      composition, bandgap, morphology, specific surface area and grain size of
      ZnTiO(3) powders. The relationship between the physicochemical property and the
      photocatalytic activity was deeply investigated, too. It is found that the
      photocatalytic activity is dependent on the phase of catalysts. The product of
      ZnTiO(3) with pure hexagonal-phase calcined at 800 degrees C for 3h exhibits the
      maximum photocatalytic performance in the photochemical degradation of the azo
      dye methyl violet under solar light irradiation. The processing parameters such
      as the concentration of catalysts and the pH value also play an important role in
      tuning the photocatalytic activity. The optimal concentration and pH value of the
      pure hexagonal-phase ZnTiO(3) is around 4g/L and 8 in a 10mg/L dye-aqueous
      solution, respectively.

PMID- 19595505
TI  - Characteristics of microporous/mesoporous carbons prepared from rice husk under
      base- and acid-treated conditions.
AB  - The study reports the preparation of activated carbon with a high surface area
      from rice husk using chemical activation with H(3)PO(4) and ZnCl(2). Activated
      carbon prepared from rice husk usually exhibits low specific surface areas due to
      its high ash content. However, experimental results show that base-leaching and
      acid-washing processes can effectively enhance the adsorption capacity of rice
      husk carbon. The study also investigates the effects of preparation parameters on
      the surface characteristics of the carbon. These parameters include the kind of
      activating agent, before and after treatment procedures, impregnation ratio and
      activation temperature. The chemical and physical properties of samples were
      examined by EA, ICP-MS, XRD, FTIR, SEM and a N(2)-adsorption meter. The surface
      areas obtained from ZnCl(2) and H(3)PO(4) activation are as high as 2434 and 1741
      m(2)/g, respectively. These values are higher than that of activated carbon
      treated with neither base nor acid (1262 and 508 m(2)/g for ZnCl(2) and H(3)PO(4)
      activation). Thermogravimetric analysis shows that the activation process can be
      divided into three parts based on temperature zones. The results of this study
      will be useful in developing resource recovery systems for agricultural biomass.

PMID- 19595507
TI  - Kinetics and equilibrium of desorption removal of copper from magnetic polymer
      adsorbent.
AB  - This study examined the desorption of copper ions, which were adsorbed on the
      magnetic polymer adsorbent (MPA) of polyvinyl acetate-iminodiacetic acid (M-PVAC
      IDA), by ethylenediaminetetraacetic acid (EDTA). Stage-wise desorptions were
      applied to remove the Cu(II) ions from the Cu(II) adsorbed M-PVAC-IDA (A-M-PVAC
      IDA). About seven desorption runs were needed to regenerate the A-M-PVAC-IDA. The
      Cu(II) desorbed M-PVAC-IDA (D-M-PVAC-IDA) was then reused to adsorb the Cu(II)
      ions from the Cu(II) ions-containing solution. The cyclic adsorption and
      desorption operations (CADOs) were performed to further elucidate the kinetics
      and equilibria of the desorption system of EDTA/A-M-PVAC-IDA and the adsorption
      system of Cu(II)-containing solution/D-M-PVAC-IDA. Two simple kinetic models, the
      pseudo-first-order equation and pseudo-second-order equation, were employed to
      simulate the kinetic behaviors of adsorption and desorption. With respect to the
      kinetics of adsorption behavior, the simulated results by both kinetic models
      exhibit good agreement with the experimental data. However, the adsorption
      capacities (q(e)) estimated by the pseudo-first-order equation are more accurate
      in comparison with those simulated by the pseudo-second-order equation. As for
      the desorption kinetics, the examination of correlation coefficients of model
      fittings of data shows that the pseudo-first-order kinetic model gives the better
      agreement for the cases with different initial solid-phase concentrations and can
      accurately compute the equilibrium concentrations of solid-phase. The values of
      q(e) after CADOs are consistent with the predicted results via the previous work,
      evidencing that the adsorption behavior and the characteristics of the
      regenerated adsorbent of D-M-PVAC-IDA were not altered. In the experiments of
      desorbing copper ions and CADOs, the desorption isotherm was set up. The
      Freundlich and Langmuir adsorption (or desorption) isotherms were used to
      simulate the equilibrium of desorption. The results indicate that the Freundlich
      equation shows better agreement with the experimental data than the Langmuir
      equation. The information thus obtained is useful for the better use of M-PVAC
      IDA on the removal of heavy mental ions of Cu(II) from the Cu(II) ion-containing
      water solution with the consideration of its regeneration.

PMID- 19595509
TI  - The use of NTA for lead phytoextraction from soil from a battery recycling site.
AB  - The application of synthetic aminopolycarboxylic acids to soil increases metal
      solubility, and therefore enhances phytoextraction. However, synthetic chelants
      degrade poorly in soil, and metal leaching threatens human and animal health. The
      aim of this study is to assess the use of a biodegradable chelant (NTA) for Pb
      phytoextraction from a soil contaminated by battery-casing disposal. EDTA was
      also included in the experiment to assess the behavior of a non-degradable
      chelant. Each synthetic chelant was applied to soil pots cultivated with maize
      plants at rates of 0, 2, 5, 10, and 20 mmol kg(-1). Soil samples were extracted
      with CaCl(2) and by sequential extraction for Pb. In addition, a soil column
      experiment was set up to study the leaching of Pb from the chelant-amended soil.
      The results showed that both NTA and EDTA were highly effective in solubilizing
      Pb from soil. The Pb distribution into soil fractions after chelant addition
      followed the sequence: Ex (exchangeable)>OM (organic matter)>AFeOx (amorphous
      iron oxides)>CFeOx (crystalline iron oxides). The 5 mmol kg(-1) dose of EDTA
      increased the Pb concentration in maize shoots to 1.1%, but it promoted
      unacceptable Pb leaching rates. On the other hand, the results showed that
      phytoremediating the site using 5 mmol kg(-1) NTA could be feasible with no
      environmental effects due to Pb leaching over a five-year period.

PMID- 19595510
TI  - Using normalized EMG to define the nociceptive flexion reflex (NFR) threshold:
      further evaluation of standardized NFR scoring criteria.
AB  - The nociceptive flexion reflex (NFR) has been used as a psychophysiological tool
      to study spinal nociceptive processes in numerous clinical and experimental
      studies. Despite widespread use of the NFR, few attempts have been made to
      empirically test and compare different scoring criteria to detect the
      presence/absence of the reflex. The present studies were conducted to address
      this issue. Study 1 (N=56 healthy participants) examined the reliability of 15
      different scoring criteria that were examined in a previous report. Study 2 (N=73
      healthy participants) extended this work by examining normalized scoring criteria
      based on biceps femoris activity unrelated to noxious stimulation (reference
      contraction, maximal contraction). In both studies, receiver operating
      characteristics (ROCs) analyses were used to evaluate and compare different
      scoring methods. The results indicate that a number of different criteria were
      acceptable for defining an NFR threshold based on the area under the ROC curve
      and its statistical significance; however, NFR Interval z score [(NFR Interval
      Mean-baseline mean)/baseline SD] emerged as the scoring criterion with the
      greatest accuracy and with cut-points that are reliable across samples. These
      findings support the application of a common NFR scoring criterion to enhance
      direct comparison of results across different research laboratories and study
      samples.

PMID- 19595512
TI  - Potential role for dog fleas in the cycle of Leishmania spp.
AB  - Several species of Leishmania spp. cause diseases in humans that range from self
      healing cutaneous lesions to fatal visceral leishmaniosis. It has been observed
      that besides being transmitted by sand flies, Leishmania spp. may also be
      transmitted by arthropods such as ticks and fleas. To investigate the possible
      role of dog fleas in the transmission of Leishmania spp., Ctenocefalides felis
      were removed from 22 dogs which were positive according to ELISA and rK-39 tests.
      A C. felis sample from each of the 22 dogs was used to infect a hamster. The 22
      hamsters were euthanized 4 months after infection with the fleas and the blood
      was subjected to ELISA to detect antibody anti-Leishmania spp., and the spleen
      samples were submitted to PCR for detection of Leishmania spp. DNA. PCR and ELISA
      were both positive in 18.1% (4/22), with PCR alone being positive in 45% (10/22)
      and ELISA alone in only 9% (2/22). These results suggest the participation of dog
      fleas in the Leishmania spp. cycle. Confirmation that C. felis indeed transmit
      leishmaniosis to dogs requires new strategies against leishmaniosis to be
      enforced by public health authorities and which focus on better ways to keep dogs
      free of fleas.

PMID- 19595511
TI  - Intestinal membrane permeability and hypersensitivity in the irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the
      underlying pathophysiology is poorly understood; however, increased intestinal
      permeability in diarrhea-predominant IBS patients has been reported. Here we
      demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased
      intestinal permeability. We have also found that increased intestinal membrane
      permeability is associated with visceral and thermal hypersensitivity in this
      subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for
      intestinal membrane permeability using the lactulose/mannitol method. All
      subjects ingested 5g of lactulose and 2g of mannitol in 100ml of water after
      which their urine was collected. We also evaluated the mean mechanical visual
      analogue scale (M-VAS) pain rating to nociceptive thermal and visceral
      stimulation in all subjects. All study participants also completed the FBDSI
      scale. Approximately 39% of diarrhea-predominant IBS patients had increased
      intestinal membrane permeability as measured by the lactulose/mannitol ratio.
      These IBS patients also demonstrated higher M-VAS pain intensity reading scale.
      Interestingly, the IBS patients with hypersensitivity and increased intestinal
      permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with
      normal membrane permeability and sensitivity (51.6 + or - 12.7) and controls (6.1
      + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal
      membrane permeability that was associated with an increased FBDSI score and
      increased hypersensitivity to visceral and thermal nociceptive pain stimuli.
      Thus, increased intestinal membrane permeability in D-IBS patients may lead to
      more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.

PMID- 19595513
TI  - Pattern of recognition of Besnoitia besnoiti tachyzoite and bradyzoite antigens
      by naturally infected cattle.
AB  - Bovine besnoitiosis is caused by the protozoan parasite Besnoitia besnoiti. Many
      recent cases have been described in different European countries, which may be
      indicative of expansion of the disease in the next few years. Many infected
      animals remain asymptomatic; therefore, serological tests are essential tools for
      diagnosis. The objective of the present work was to identify B. besnoiti
      tachyzoite and bradyzoite immunodominant antigens (IDAs). IDAs were recognised by
      SDS-PAGE under reducing conditions and Western blot analysis. Positive sera from
      symptomatic (n=18) and asymptomatic (n=18) cattle came from herds endemically
      infected by B. besnoiti and were confirmed positive by IFAT, whereas negative
      sera (n=4) came from besnoitiosis-free herds and were also confirmed negative by
      IFAT. Up to 28 tachyzoite antigens in the range of 8.5-190.8 kDa were recognised.
      Based on the frequency of recognition, six IDAs (14.2, 33, 37.1, 39.6, 46.3 and
      190.8 kDa) were identified. The 37.1 kDa antigen was recognised by 100% of sera,
      usually as an intense band. On the other hand, 30 bradyzoite antigens in the
      range of 8.5-187.9kDa were detected. Seven bradyzoite IDAs (8.5, 15.1, 16.8,
      19.0, 34.7, 38.6 and 124.4 kDa) were identified and two of them (15.1 and 16.8
      kDa) were considered the most immunogenic ones. Additionally, sera from animals
      with clinical symptoms recognised a significantly higher number of bradyzoite
      antigens. Finally, significant cross-reactions with other closely related
      apicomplexan parasites were not detected. This is the first description of B.
      besnoiti bradyzoite antigens. In addition, the identification of tachyzoite and
      bradyzoite IDAs may be useful for the development of vaccines and diagnostic
      tools for differentiating between acute and chronic infections. Further proteomic
      studies are needed in order to identify stage-specific proteins.

PMID- 19595514
TI  - Associations between psychosocial state variables and the cortisol awakening
      response in a single case study.
AB  - The current study investigated intra-individual associations between psychosocial
      state variables and the cortisol awakening response (CAR) in a detailed case
      study of a 27-year-old healthy male (TS) carried out over 50 measurement days,
      occurring at 3-day intervals. Quantitative diaries capturing psychosocial states
      were filled out on the evening before each study day as well as 45min post
      awakening on the study day. On each study day, salivary free cortisol was
      determined at 0, 15, 30, and 45min post-awakening. Relationships between cortisol
      measures and psychosocial variables were analysed using correlation analyses and
      relative predictive input of independent variables was further determined using
      linear regression analysis. Significant relationships were found between
      psychosocial state variables and the dynamic of the CAR (area under increase
      curve; AUC(I)). The final regression model for the AUC(I) (explaining
      approximately 22% of its variability), included an inverse relationship with the
      level of prior-day happiness and a positive relationship with study-day
      anticipations of the level of obligations/no leisure. The results are discussed
      within the context of previous evidence and potential implications for cross
      sectional research are highlighted.

PMID- 19595516
TI  - Mature mediastinal teratoma with subtotal unidirectional pancreatic
      differentiation.
AB  - Tumor-like lesions of the mediastinum consisting exclusively of mature pancreatic
      tissue are rare. Most authors regard these lesions as developmental
      abnormalities. We report the case of a 17-year-old male who presented with
      progressive dyspnea due to a large mediastinal tumor with accompanying
      pericardial effusion. Percutaneous core needle biopsies showed differentiated
      pancreatic tissue with chronic inflammation and cystic transformation. On this
      basis, heterotopic pancreatic tissue of the mediastinum, a lesion occasionally
      reported in the literature, was suspected and the lesion was excised. The
      histopathological workup of the surgically excised lesion, in the first place,
      supported the primary diagnosis. However, after extensive sampling of the lesion,
      the diagnosis had to be changed to mature teratoma with subtotal unidirectional
      pancreatic differentiation. We hypothesize that at least some of those cases
      reported in the literature as "heterotopic pancreatic tissue of the mediastinum"
      may be in fact unidirectionally differentiated teratomas and should therefore be
      regarded and treated as true neoplasms rather than developmental abnormalities.

PMID- 19595515
TI  - Race differences in factors relating to smoking initiation.
AB  - To investigate race differences in retrospectively-reported early smoking
      experiences, we studied African-American (n=48) and Caucasian (n=155) current
      smokers who participated in a study designed to identify phenotypic and genotypic
      factors associated with smoking. Compared with Caucasian smokers, African
      American smokers were less educated (mean+/-s.e.m.: 13.3+/-0.25 vs. 14.3 +/-
      0.16; p<.01), had higher BMI (28.9+/-1.06 vs. 26.7+/-0.52; p<.05), and smoked
      significantly fewer cigarettes/day (14.1+/-1.00 vs. 18.4+/-0.74; p<.01). Ninety
      percent of African-American smokers consumed menthol cigarettes, as opposed to
      25% of Caucasian smokers. African-American smokers were significantly older than
      Caucasian smokers upon initial smoking experimentation (17.4+/-1.1 vs. 14.7+/
      0.3; p<.05) and onset of regular smoking (19.7+/-0.9 vs. 17.4+/-0.4; p<.05).
      African-American smokers were significantly more likely than Caucasian smokers to
      endorse global pleasurable sensations (48% vs. 30%; p<.05), "pleasurable rush or
      buzz" (62% vs. 43%; p<.05), and "relaxing" (45% vs. 27%; p<.05) as early
      experiences with smoking, whereas Caucasian smokers were marginally more likely
      to report dizziness and difficulty inhaling (61% vs. 45%; p<.10 and 48% vs. 31%;
      p<.10, respectively). Caucasian smokers were significantly more likely to endorse
      friends (6.9+/-0.2 vs. 4.8+/-0.4; p<.0001) and "perk me up" (4.2+/-0.3 vs. 3.1+/
      0.4; p<.05) and marginally more likely to endorse buzz (4.2+/-0.2 vs. 3.4+/-0.5;
      p<.10) as reasons for starting to smoke. Further research is needed to determine
      the relative contributions of genetic, developmental, and socio-cultural factors
      to these findings.

PMID- 19595517
TI  - Diffusion tensor imaging in cocaine dependence: regional effects of cocaine on
      corpus callosum and effect of cocaine administration route.
AB  - Recent studies demonstrated that diffusion tensor imaging (DTI) can provide
      information regarding white matter integrity of the corpus callosum (CC). In this
      study, DTI parameters were compared between cocaine dependent subjects (CDs) and
      non-drug using controls (NCs) in midsagittal CC. DTI images were acquired from 19
      CDs and 18 age-matched NCs. The midsagittal CC was segmented into: genu, rostral
      body, anterior midbody, posterior midbody, isthmus, and splenium. Linear mixed
      models analyses showed that, relative to NCs, CDs had lower fractional anisotropy
      (FA), higher radial diffusivity (lambda(perpendicular)), and higher mean
      diffusivity (D(av)) in the isthmus; higher lambda(perpendicular) and D(av) in the
      rostral body; and lower FA in the splenium. After including mass of lifetime
      alcohol use in the mixed model analysis of covariance (ANCOVA) as a covariate,
      significant between group differences in lambda(perpendicular) in the rostral
      body and isthmus remained. These results suggest that alterations in
      lambda(perpendicular) in the rostral body and isthmus were mainly due to cocaine
      use, consistent with previous studies showing that cocaine may alter myelin
      integrity. Between group differences in FA in the isthmus and splenium, and D(av)
      in the rostral body and isthmus became non-significant after inclusion of alcohol
      use as a covariate. This is suggestive of alcohol influencing these values, or
      may be related to the decreased degrees of freedom for these effects. Consistent
      with clinical data of greater severity of drug use in smoked versus intranasal
      cocaine, subjects who smoked cocaine showed lower FA and higher
      lambda(perpendicular) compared to intranasal CDs.

PMID- 19595518
TI  - Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent
      outpatients.
AB  - BACKGROUND: A high smoking prevalence has been registered among alcoholics. It
      has been pointed out that alcoholic smokers may have a more severe course and
      greater severity of alcoholism. This study aims at comparing smoking and non
      smoking alcoholics in terms of treatment outcomes and verifying the efficacy of
      topiramate and naltrexone to decrease the use of cigarettes among alcoholic
      smokers. METHODS: The investigation was a double-blind, placebo-controlled, 12
      week study carried out at the University of Sao Paulo, Brazil. The sample
      comprised 155 male alcohol-dependent outpatients (52 non-smokers and 103
      smokers), 18-60 years of age, with an International Classification of Diseases
      (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period,
      the patients randomly received placebo, naltrexone (50mg/day) or topiramate (up
      to 300 mg/day). Only the alcoholic smokers who adhered to the treatment were
      evaluated with reference to the smoking reduction. RESULTS: Cox regression
      analysis revealed that the smoking status among alcoholics increased the odds of
      relapse into drinking by 65%, independently of the medications prescribed, using
      the intention-to-treat method. Topiramate showed effectiveness to reduce the
      number of cigarettes smoked when compared to placebo among adherent patients
      (mean difference=7.91, p<0.01). There were no significant differences between the
      naltrexone group and the placebo group. CONCLUSIONS: The results of this study
      confirm that the treatment is more challenging for smoking alcoholics than for
      non-smoking ones and support the efficacy of topiramate in the smoking reduction
      among male alcoholic smokers who adhered to the treatment.

PMID- 19595519
TI  - High HEV presence in four different wild boar populations in East and West
      Germany.
AB  - Swine Hepatitis E virus (HEV) can be transmitted from pigs to humans causing
      hepatitis. A high prevalence of HEV in wild boar populations is reported for
      several European countries, but actual data for Germany are missing. During the
      hunting season from October to December 2007 liver, bile and blood samples were
      collected from wild boars in four different German regions. The samples were
      tested for HEV RNA by quantitative PCR (qPCR) and anti-HEV IgG antibodies by two
      different ELISAs and a Line immunoassay. A seroprevalence of 29.9% using ELISA
      and 26.2% in the Line immunoassay was determined. The seroprevalence rate varied
      greatly within the analyzed regions. However, qPCR analysis revealed a higher
      prevalence of 68.2% positive animals with regional differences. Surprisingly,
      also adult wild sows and wild boars were highly HEV positive by qPCR. Compared to
      liver and serum samples, bile samples showed a higher rate of positive qPCR
      results. Sequencing and phylogenetic analysis of a 969nt fragment within ORF 2
      revealed that all isolates clustered within genotype 3 but differed in the
      subtype depending on the hunting spot. Isolates clustered within genotypes 3i,
      3h, 3f and 3e. Within one population HEV isolates were closely related, but
      social groups of animals in close proximity might be infected with different
      subtypes. Two full-length genomes of subtypes 3i and 3e from two different
      geographic regions were generated. The wild boar is discussed as one of the main
      sources of human autochthonous infections in Germany.

PMID- 19595520
TI  - Deletion of sodCI and spvBC in Salmonella enterica serovar Enteritidis reduced
      its virulence to the natural virulence of serovars Agona, Hadar and Infantis for
      mice but not for chickens early after infection.
AB  - Salmonella enterica serovars Typhimurium, Enteritidis, Dublin, Choleraesuis or
      Gallinarum can colonise liver and spleen in particular hosts while infections
      with serovars Infantis, Agona, Hadar, etc. are usually limited to
      gastrointestinal tract. Reasons for this behavior are unknown, although it has
      been shown that sodCI and spv genes exhibit a strict distribution between more
      and less virulent serovars and they influence Salmonella virulence. However to
      what extent the presence or absence of these genes is associated with the
      increased virulence of serovars which possess them has never been addressed
      experimentally. In this study we therefore first confirmed the exclusive
      association of spvB and sodCI genes with the former group of serovars. In the
      next step we removed these two genes from S. Enteritidis genome and compared the
      virulence of such a mutant with the virulence of S. Infantis, S. Agona and S.
      Hadar for chickens and highly sensitive Balb/C mice. Single strain infection
      showed that the deletion of these two genes from S. Enteritidis resulted in the
      reduction of its virulence for mice but not for chickens. Mixed infection further
      confirmed these observations and indicated that in mice but not in chickens the
      virulence of sodCI and spv mutant was reduced to the natural virulence of
      serovars Infantis, Agona and Hadar. Although sodCI and spv genes do not influence
      S. Enteritidis virulence for chickens directly, they may be of an indirect effect
      through the increased persistence of S. Enteritidis in mice and increased
      probability of the reintroduction of S. Enteritidis into poultry flocks.

PMID- 19595521
TI  - Detection of Bartonella spp. in wild rodents in Israel using HRM real-time PCR.
AB  - The prevalence of Bartonella spp. in wild rodents was studied in 19 geographical
      locations in Israel. One hundred and twelve rodents belonging to five species
      (Mus musculus, Rattus rattus, Microtus socialis, Acomys cahirinus and Apodemus
      sylvaticus) were included in the survey. In addition, 156 ectoparasites were
      collected from the rodents. Spleen sample from each rodent and the ectoparasites
      were examined for the presence of Bartonella DNA using high resolution melt (HRM)
      real-time PCR. The method was designed for the simultaneous detection and
      differentiation of eight Bartonella spp. according to the nucleotide variation in
      each of two gene fragments (rpoB and gltA) and the 16S-23S intergenic spacer
      (ITS) locus, using the same PCR protocol which allowed the simultaneous
      amplification of the three different loci. Bartonella DNA was detected in spleen
      samples of 19 out of 79 (24%) black rats (R. rattus) and in 1 of 4 (25%) Cairo
      spiny mice (A. cahirinus). In addition, 15 of 34 (44%) flea pools harbored
      Bartonella DNA. Only rat flea (Xenopsyla cheopis) pools collected from black rats
      (R. rattus) were positive for Bartonella DNA. The Bartonella sp. detected in
      spleen samples from black rats (R. rattus) was closely related to both B.
      tribocorum and B. elizabethae. The species detected in the Cairo spiny mouse (A.
      cahirinus) spleen sample was closely related to the zoonotic pathogen, B.
      elizabethae. These results indicate that Bartonella species are highly prevalent
      in suburban rodent populations and their ectoparasites in Israel. Further
      investigation of the prevalence and zoonotic potential of the Bartonella species
      detected in the black rats and the Cairo spiny mouse is warranted.

PMID- 19595522
TI  - Vaccine efficacy and immune response to swine influenza virus challenge in pigs
      infected with porcine reproductive and respiratory syndrome virus at the time of
      SIV vaccination.
AB  - The objective of this study was to assess the effect of concurrent infection with
      porcine reproductive and respiratory syndrome virus (PRRSV) on the efficacy of an
      inactivated swine influenza virus (SIV) vaccine. Eight groups of pigs were
      infected with a virulent PRRSV isolate either between the two SIV vaccines or at
      the time of SIV challenge. Control groups included SIV vaccination without PRRSV
      and pigs infected with SIV and/or PRRSV. Pigs infected with PRRSV during
      vaccination showed increased levels of macroscopic and microscopic lesions
      compared to pigs vaccinated against and challenged with only SIV indicating
      decreased SIV vaccine efficacy. In addition, pigs vaccinated in the presence of
      PRRSV showed increased clinical disease and shedding of SIV during the acute
      phase of SIV infection. No alterations in the systemic or local antibody response
      to either SIV vaccination or challenge were observed. These findings demonstrate
      that PRRSV infection has a significant impact on SIV vaccine efficacy that may be
      important for disease control.

PMID- 19595523
TI  - Variation in shedding of Oxalobacter formigenes in feces of healthy dogs.

PMID- 19595524
TI  - Pregnancy loss in heifers after artificial insemination with frozen-thawed, sex
      sorted, re-frozen-thawed dairy bull sperm.
AB  - The use of sex-sorted sperm by the dairy industry is often limited by the
      geographical distance between potential sires and the sex-sorting facility. One
      method that may be used to overcome this limitation is sex-sorting sperm that
      have been previously frozen, or transported to the sorting facility as cooled
      liquid semen. In this study the in vivo fertility of frozen-thawed, sex-sorted,
      re-frozen-thawed (FSF) and cooled, sex-sorted, frozen-thawed (CSF) bull sperm was
      determined after artificial insemination (AI) of Holstein heifers. Semen from two
      bulls was frozen in straws, or transported to the sorting facility in an egg yolk
      diluent at 5 degrees C over 24h. Thawed or re-warmed semen was processed through
      a PureSperm density gradient, and sperm were sorted for sex and frozen (2 or 4 x
      10(6)sperm/straw). Synchronised heifers (n=183) were inseminated with either non
      sorted control sperm (Control; 20 x 10(6) dose) or with FSF or CSF 'X' sperm (2
      or 4 x 10(6)/dose). Pregnancy rates (detected at 7-9 weeks) after AI with control
      sperm were higher than with FSF or CSF sperm (57.4 vs. 4.1 and 7.3% respectively;
      p<0.001). There was a significant difference between bulls (Bull 1: Control
      63.0%, FSF 8.6%, CSF 10.0%; Bull 2: Control 45.5%, FSF 0%, CSF 4.8%; p=0.001).
      Five out of six (83.3%) pregnancies produced with sexed sperm were lost after
      pregnancy diagnosis. The exception was one heifer inseminated with CSF sperm (2
      million sperm dose), which produced a heifer calf. In the non-sorted control
      group, three pregnancies were lost (8.3%) and three stillbirths occurred (8.3%).
      The low fertility and high rate of pregnancy loss in the sexed groups, in
      addition to environmental influences, may be attributed to impaired sperm
      function caused by sex-sorting and re-freezing, leading to poor embryo quality or
      altered gene expression. More precise timing of insemination and higher sperm
      doses might improve the fertility of FSF sperm. Moreover, the in vitro function
      of double-frozen sexed compared with non-sorted sperm requires further
      investigation.

PMID- 19595525
TI  - Sex-related differences in pain.
AB  - This article provides an overview of sex-related differences in musculoskeletal
      pain and the role sex hormones and response to analgesic drugs may play in these
      differences. Some common pain conditions that include temporomandibular
      disorders, rheumatoid arthritis, fibromyalgia syndrome and tension-type and
      migraine headaches, show fairly marked sex-related differences in their
      occurrence, however, with the exception of rheumatoid arthritis, these pain
      conditions are also characterized by a lack of understanding of their basic
      underlying pathophysiology. The association of pain symptoms of these
      musculoskeletal pain conditions with the reproductive cycle of women is strongly
      suggestive of a role of the estrogens and/or progesterones, the main female sex
      hormones, in sex-related differences in pain. Nevertheless, an alternative
      suggestion that testosterone, the major male sex hormone, protects men from these
      chronic musculoskeletal pain conditions, has also been made. Indeed, emerging
      evidence suggests that both male and female sex hormones may contribute to the
      marked sex-related differences in the occurrence of certain musculoskeletal pain
      conditions. Men and women also appear to differ in response to pain treatment
      with certain analgesic drugs. The mechanistic basis for these sex-related
      differences is not entirely understood but sex hormones are thought to be one of
      the influencing factors. An improved understanding of mechanisms which underlie
      sex-related differences in musculoskeletal pain and response to analgesic drugs
      should permit improved pain management strategies for male and female
      musculoskeletal pain patients in the clinical setting.

PMID- 19595527
TI  - Mechanism of febrile seizure.

PMID- 19595526
TI  - Value of histological study in the fronto-sphenoidal suture for the age
      estimation at the time of death.
AB  - The macroscopic study of cranial sutures is one of the methods that may be used
      in forensic anthropology to estimate age at the time of death. The present study
      aims at assessing the value of a microscopic analysis of the fronto-sphenoidal
      suture (FSS) sampled at autopsy, to determine both the physiological mechanisms
      responsible for the FFS closing during ageing and its value in the estimation of
      age at the time of death. We assessed the vascular capital as well as the
      apoptosis of conjunctive cells intervening as parameters in the physiological
      mechanism involved in cell ageing, in a population of individuals, whose gender
      and age was known. The FSS analysis was performed after decalcification and
      standard histological study, respectively with immunohistochemistry (Factor Von
      Willebrand antibody) VWF and (TdT-mediated dUTP nick end labelling) TUNEL method
      and caspase-3 immunohistochemical expression. In this study we found a
      significant reversed correlation between the degree of vascular expression of VWF
      and age at the time of death. There was also a significant positive correlation
      between the degree of apoptosis in the conjunctive cells of the FSS and age at
      the time of death. According to these results, suture closing during ageing can
      be explained by these two combined mechanisms of conjunctival apoptosis and
      vascular involution. Thus, the findings justify the study of closing sutures to
      estimate age at the time of death. Besides, it also enabled us to establish
      linear regressions. The vascular expression of the VWF enables to estimate an
      individual's age at the time of his death more or less at about 1.55 years,
      offering an interesting perspective both in forensic pathology and anthropology.

PMID- 19595528
TI  - Low-dose adaptive sequential scan for dual-source CT coronary angiography in
      patients with high heart rate: comparison with retrospective ECG gating.
AB  - PURPOSE: To explore feasibility of dual-source CT (DS-CT) prospective ECG-gated
      coronary angiography in patients with heart rate (HR) higher than 70beat per
      minute (bpm), and evaluate image quality and radiation dose with comparison to
      retrospective ECG-gated spiral scan. MATERIALS AND METHODS: One hundred patients
      who underwent DS-CT coronary angiography (DS-CTCA) with mean HR higher than 70bpm
      but below 110bpm were enrolled in the study, 50 were scanned by adaptive
      sequential scan and another 50 were analyzed by retrospectively gated CT scan.
      The imaging quality of coronary artery segments in the two groups was evaluated
      using a four-point grading scale by two independent reviewers. Patient radiation
      dose was calculated by multiplying dose length product by conversion coefficient
      of 0.017. RESULTS: There was no significant difference between the two groups for
      mean HR (p=0.305), HR variability (p=0.103), body mass index (p=0.472), and scan
      length (p=0.208). There was good agreement for image quality scoring between the
      two reviewers (Kappa=0.72). Coronary evaluability of adaptive sequential scan was
      99.7% (608 of 610 segments), while that of retrospective gated scan was 98.7%
      (614 of 622 segments), showing similar coronary evaluability (p=0.061). Effective
      doses of adaptive sequential scan and retrospective gated scan were 5.1+/-1.6 and
      11.8+/-4.5mSv, respectively (p<0.001), showing that adaptive sequential scan
      reduced radiation dose by 57% compared with that of retrospective gated scan.
      CONCLUSIONS: In patients with 70-110bpm HR, DS-CTCA adaptive sequential scan
      shows similar image quality as retrospective ECG-gated spiral scan with 57%
      reduction of radiation dose.

PMID- 19595529
TI  - Development and validation of a stability indicating LC method for the assay and
      related substances determination of exemestane, an aromatase inhibitor.
AB  - A selective stability indicating HPLC method was developed and validated for
      quantification of impurities (process related and degradants) and assay
      determination of Exemestane. Stability indicating power of the method was
      established by forced degradation experiments and mass balance study. The
      chromatographic separation was achieved with Hypersil BDS-C-18 using gradient
      elution. The developed method is validated for parameters like accuracy,
      linearity, LOD, LOQ, ruggedness. Box-Behnken experimental design was applied to
      check the robustness of the method.

PMID- 19595530
TI  - Simultaneous determination of phytoestrogens and key metabolites in breast cancer
      patients' urine by liquid chromatography-tandem mass spectrometry.
AB  - A novel, selective and sensitive liquid chromatography-tandem mass spectrometry
      method has been developed and validated for the simultaneous determination of
      phytoestrogens and their key metabolites in human urine in this study. This
      method includes internal standard (IS) screening, analytical sample preparation
      procedure establishment, and linear range investigation. The analytical sample
      was extracted by liquid-liquid extraction from urine sample. The phytoestrogens
      and related key metabolites were separated with Agilent Zorbax Eclipse XDB-C18
      chromatographic column using methanol and water as mobile phase. The Quattro
      premier MICROMASS mass spectrometer in negative ion selected reaction monitoring
      (SRM) mode using electrospray ionization was applied to detect the phytoestrogens
      and key metabolites. To validate the developed liquid chromatography-tandem mass
      spectrometry method, the intra- and inter-day precisions, specificity,
      sensitivity, reproducibility, and sample detective concentration range were
      evaluated. This is the first reported phytoestrogens analysis and validation
      study that demonstrates the feasibility of using liquid chromatography
      electrospray ionization mass spectrometry to simultaneously analyze ten analytes
      including both phytoestrogens and their key metabolites in urine samples
      collected for epidemiological studies in human.

PMID- 19595531
TI  - Combination of stromal-derived factor-1alpha and vascular endothelial growth
      factor gene-modified endothelial progenitor cells is more effective for ischemic
      neovascularization.
AB  - BACKGROUND: Recruitment and entrapment of bone marrow-derived endothelial
      progenitor cells (EPCs) is important in vascular endothelial growth factor (VEGF)
      induced angiogenesis. EPC mobilization and differentiation are modulated by
      stromal-derived factor-1alpha (SDF-1alpha/CXCL12), another important chemokine.
      In this study, we investigated the hypothesis that SDF-1alpha and VEGF might act
      synergistically on EPC-mediated vasculogenesis. METHODS: EPCs were isolated and
      cultured from human peripheral blood, then transduced with retroviral vectors
      pBabe containing human VEGF(165) complimentary DNA (Td/V-EPCs) and pBabe wild
      type (Td/p-EPCs). EPC migration activity was investigated with a modified Boyden
      chamber assay. EPC apoptosis induced by serum starvation was studied by annexin V
      assays. The combined effect of local administration of SDF-1alpha and Td/V-EPC
      transplantation on neovascularization was investigated in a murine model of hind
      limb ischemia. RESULTS: Over-expression of hVEGF(165) increased SDF-1alpha
      mediated EPC migration. SDF-1alpha-mediated migration was significantly increased
      when EPCs were modified with VEGF (Td/V-EPCs) vs when VEGF was not present (Td/p
      EPCs) or when VEGF alone was present (Td/V-EPCs; 196.8 +/- 15.2, 81.2 +/- 9.8,
      and 67.4 +/- 7.4/mm(2), respectively P < .001). SDF-1alpha combined with VEGF
      reduced serum starvation-induced apoptosis of EPCs more than SDF-1alpha or VEGF
      alone (P < .001). To determine the effect of this combination in vivo, SDF-1alpha
      was locally injected alone into the ischemic hind limb muscle of nude mice or
      combined with systemically injected Td/V-EPCs. The SDF-1alpha plus VEGF group
      showed significantly increased local accumulation of EPCs, blood-flow recovery,
      and capillary density compared with the other groups. The ratio of
      ischemic/normal blood flow in Td/V-EPCs plus SDF-1alpha group was significantly
      higher (P < .01), as was capillary density (capillaries/mm(2)), an index of
      neovascularization (Td/V-EPCs plus SDF-1alpha group, 863 +/- 31; no treatment,
      395 +/-13; SDF-1alpha, 520 +/- 29; Td/p-EPCs, 448 +/- 28; Td/p-EPCs plus SDF
      1alpha, 620 +/- 29; Td/V-EPCs, 570 +/- 30; P < .01). To investigate a possible
      mechanistic basis, we showed that VEGF up-regulated the receptor for SDF-1alpha,
      CXCR4, on EPCs in vitro. CONCLUSION: The combination of SDF-1alpha and VEGF
      greatly increases EPC-mediated angiogenesis. The use VEGF and SDF-1alpha
      together, rather than alone, will be a novel and efficient angiogenesis strategy
      to provide therapeutic neovascularization.

PMID- 19595532
TI  - Restenosis after renal artery angioplasty and stenting: incidence and risk
      factors.
AB  - BACKGROUND: Management of renal artery stenosis (RAS) with primary renal artery
      percutaneous angioplasty and stenting (RA-PTAS) is associated with a low risk of
      periprocedural death and major complications; however, restenosis develops in a
      subset of patients and repeat intervention may be required. We examined the
      incidence of restenosis after RA-PTAS and associations with clinical factors.
      METHODS: Consecutive patients undergoing RA-PTAS for hemodynamically significant
      atherosclerotic RAS associated with hypertension or ischemic nephropathy, or
      both, between October 2003 and September 2007 were identified from a registry.
      Restenosis was defined using duplex ultrasound (DUS) imaging as a renal artery
      postintervention peak systolic velocity (PSV) >or=180 cm/s. The incidence and
      temporal distribution of restenosis was analyzed using survival analysis based on
      treated kidneys. Associations between clinical factors and recurrent stenosis
      were examined using proportional hazards regression. RESULTS: RA-PTAS was
      performed on 112 kidneys for atherosclerotic RAS during the study period. Initial
      postintervention renal artery DUS imaging confirming PSV <180 cm/s in 101
      kidneys, which formed the basis of this analysis. Estimated restenosis-free
      survival was 50% at 12 months and 40% at 18 months. Decreased risk of restenosis
      was associated with preoperative statin use (hazard ratio [HR], 0.35; 95%
      confidence interval [CI], 0.16-0.74; P = .006) and increased preoperative
      diastolic blood pressure (DBP; HR, 0.70 per 10-mm Hg increase in preoperative
      DBP; 95% CI, 0.49-0.99; P = .049). No other factors assessed were associated with
      restenosis. CONCLUSION: Restenosis occurs in a substantial number of patients
      treated with RA-PTAS. Preoperative statin medication use and increased
      preoperative DBP are associated with reduced risk of restenosis. In the absence
      of contraindications, statins should be considered standard therapy for patients
      with atherosclerotic renal artery stenosis.

PMID- 19595534
TI  - Anatomical repair of a congenital aneurysm of the distal abdominal aorta in a
      newborn.
AB  - Congenital (primary) neonatal abdominal aortic aneurysm (AAA) is an extremely
      rare truncular arterial abnormality among numerous congenital vascular
      malformations. Only seven cases have been reported as congenital origin in
      newborns. This report presents the case of a male infant in whom a 33-mm
      congenital AAA was diagnosed prenatally and was successfully treated 10 days
      after birth without exogenous graft material or aneurysmorrhaphy. Follow-up study
      at 39 months demonstrated excellent clinical, ultrasound scan, and computed
      tomography scan findings. Anatomic reconstruction with native vessels is the
      preferred surgical technique to ensure the child's potential for harmonious
      growth.

PMID- 19595533
TI  - Contemporary management of atherosclerotic renovascular disease.
AB  - Atherosclerotic renovascular disease (aRVD) is an increasingly recognized cause
      of severe hypertension and declining kidney function. Patients with aRVD have
      been demonstrated to have an increased risk of adverse cardiovascular events
      compared with patients without aRVD. For these reasons, >45,000 renal artery
      revascularization procedures are performed annually, with significant growth
      observed in the number of procedures performed each year. The efficacy of
      contemporary revascularization therapies in the treatment of aRVD is unproven and
      controversial, with no level I data to support current practices. Lower-level
      data suggest that kidney function improvement is a key indicator of subsequent
      improved survival free of adverse cardiovascular events and dialysis, and that
      observed improvements of hypertension confer, at best, limited benefit. This
      review focuses on existing data on the management of aRVD, including data from
      completed and ongoing randomized clinical trials. This review also examines other
      existing data regarding aRVD that may guide current treatment and future research
      efforts into this significant clinical and public health problem until widely
      accepted level I evidence emerges.

PMID- 19595535
TI  - Symptomatic, acute aortocaval fistula complicating an infrarenal aortic aneurysm.

PMID- 19595536
TI  - Superficial venous aneurysms of the small saphenous vein.
AB  - Historically, superficial venous aneurysms of the lower extremities are
      considered rare. However, owing to the increased use of duplex ultrasound
      imaging, these entities are being recognized more frequently. The clinical
      significance of superficial aneurysms is poorly defined; yet, pulmonary emboli
      arising from superficial aneurysms have been reported. Symptomatic patients
      typically complain of the sequelae of reflux, such as edema, pain, mass, and
      varicosities. Current treatment consists of simple open excision. We report two
      cases of small saphenous vein aneurysm and provide review of its pathophysiology,
      presentation, diagnostic evaluation, and therapy.

PMID- 19595538
TI  - Perioperative outcomes and amputation-free survival after lower extremity bypass
      surgery in California hospitals, 1996-1999, with follow-up through 2004.
AB  - OBJECTIVE: There are very few population-based studies of long-term outcomes
      after lower extremity (LE) bypass graft surgery. This study analyzes
      perioperative and long-term limb salvage and amputation-free survival outcomes
      for patients undergoing initial aortoiliac or femoropopliteal bypass graft
      surgery in California hospitals from 1996 to 1999. METHODS: Administrative data
      with encrypted identifiers were used to identify a chronologically first, index
      admission of all patients undergoing LE bypass procedures for occlusive disease
      from 1996 to 1999. A 1993 to 1995 look-back period was used to exclude patients
      who had undergone prior bypass surgery or amputation procedures. Patients with
      incident procedures were then followed forward to determine subsequent
      hospitalizations and vital status through 2004. The study comprised 28,128
      patients discharged from 345 California hospitals with a median 61.5-month follow
      up. Risk factors included demographic characteristics, comorbid conditions,
      admission type, gangrene or ulceration, operation level, hospital LE bypass
      surgery volume, and year of discharge. Logistic regression was used to analyze 30
      day outcomes, and Kaplan-Meier analysis and Cox proportional hazard models were
      used to analyze amputation-free survival. RESULTS: Overall 30-day mortality was
      4.3, and the 30-day major amputation rate was 2.6%. Limb salvage was 81.9% at 5
      years and 76.4% at 9 years. Amputation-free survival was 51.5% at 5 years and
      34.1% at 9 years. Risk factors were generally similar for both perioperative and
      late outcomes. Advanced age, higher comorbidity level, gangrene, and emergency or
      nursing home admission conferred significantly greater risk. Hospital volume was
      associated with both perioperative and late outcomes. African American and
      Hispanic patients had much higher amputation rates but did not have higher
      mortality risk after controlling for baseline severity of illness. CONCLUSIONS:
      Long-term outcomes of LE bypass surgery were superior for high-volume hospital
      patients. Graft surveillance and risk factor follow-up care provide a major
      opportunity for quality improvement efforts. The contrast between traditional
      limb salvage and amputation-free survival outcomes raises questions about the
      value of surgical treatment, particularly for patients with limited life
      expectancy and without coding of tissue loss or critical limb ischemia.

PMID- 19595540
TI  - Long-term safety of left renal vein division and ligation to expedite complex
      abdominal aortic surgery.
AB  - BACKGROUND: Left renal vein division and ligation (LRVDAL) is performed to
      facilitate complex abdominal aortic surgery. Surgeons restore continuity of the
      vein due to concern that ligation could cause renal compromise or hematuria.
      However, we report the short and long-term safety of left renal vein division and
      ligation. METHOD: Between 1992 and 2007, we divided the left renal vein in 56
      patients (40 males, 16 females) ages 57 to 84 (average 74-years-old) who were
      treated for aortic occlusive disease (9) or abdominal aortic aneurysm (47).
      Patients requiring concomitant renal artery reconstruction were excluded from
      this review. Suprarenal cross-clamp was used in 51 patients with temporary vessel
      loop control of the renal arteries. Creatinine (Cr) and glomerular filtration
      rates (eGFR) were measured pre-, post-, and long-term after surgery. Outpatient
      records of all patients that had survived more than 12 months were also reviewed
      in order to evaluate the late effects on renal function or symptoms possibly
      related to LRVDAL. RESULTS: Median procedure duration was 157 (61-375) minutes.
      Median cross-clamp time was 16 (10-45) minutes. Median intensive care unit (ICU)
      and hospital length of stays were 2 (1-11) days and 7 (4-58) days, respectively.
      There were no deaths. There were no complications directly related to renal vein
      ligation. Hematuria, seen in 2 patients, was a result of traumatic insertion of a
      Foley catheter. Median pre-op and discharge Cr levels were 1.1 mg/dL (0.7-2.4
      mg/dL) and 1.1 mg/dL (0.6-2.1 mg/dL), respectively (P < .5). Median change in Cr
      was 0.0 mg/dL and only increased in 14 patients (maximum increase 0.9 mg/dL).
      Median pre-op and discharge eGFR was 61 mL/minute (28-137 mL/minute/1.73 m2) and
      67 mL/minute (32-138 mL/minute/1.73 m2), respectively (P < .5). Cr and eGFR in
      the 2 patients with a Cr of >2.0 mg/dL remained unchanged post-op. Only 2
      patients with a Cr of <2.0 mg/dL had a post-op Cr >2.0 mg/dL and both returned to
      normal by day 3 post-op. Thirty-six patients have been followed for more than a
      year (median 34.5 months, maximum 144 months) and Cr has remained stable in all
      but 2 patients. These 2 patients, both with a pre-op Cr of 1.5 mg/dL,
      subsequently developed Cr levels of 2.1 mg/dL and 2.4 mg/dL but maintained
      baseline Cr levels for 25 and 34 months, respectively, before demonstrating these
      elevated levels which have proven to be unrelated to renal vein ligation.
      Hematuria and flank pain have never been recorded after discharge. CONCLUSION:
      Restoration of left renal vein continuity after LRVDAL may be unnecessary since
      renal compromise and hematuria was not encountered in this long-term analysis.

PMID- 19595541
TI  - The Semmes Weinstein monofilament examination as a screening tool for diabetic
      peripheral neuropathy.
AB  - OBJECTIVE: The purpose of this systematic review is to evaluate current evidence
      in the literature on the efficacy of Semmes Weinstein monofilament examination
      (SWME) in diagnosing diabetic peripheral neuropathy (DPN). METHODS: The PubMed
      database was searched through August 2008 for articles pertaining to DPN and SWME
      with no language or publication date restrictions. Studies with original data
      comparing the diagnostic value of SWME with that of one or more other modalities
      for DPN in patients with diabetes mellitus were analyzed. Data were extracted by
      two independent investigators. Diagnostic values were calculated after
      classifying data by reference test, SWME methodology, and diagnostic threshold.
      RESULTS: Of the 764 studies identified, 30 articles were selected, involving 8365
      patients. There was great variation in both the reference test and the
      methodology of SWME. However, current literature suggests that nerve conduction
      study (NCS) is the gold standard for diagnosing DPN. Four studies were identified
      which directly compared SWME with NCS and encompassed 1065 patients with, and 52
      patients without diabetes mellitus. SWME had a sensitivity ranging from 57% (95%
      confidence interval [CI], 44% to 68%) to 93% (95% CI, 77% to 99%), specificity
      ranging from 75% (95% CI, 64% to 84%) to 100% (95% CI, 63% to 100%), positive
      predictive value (PPV) ranging from 84% (95% CI, 74% to 90%) to 100% (95% CI, 87%
      to 100%), and negative predictive value (NPV) ranging from 36% (95% CI, 29% to
      43%) to 94% (95% CI, 91% to 96%). CONCLUSIONS: There is great variation in the
      current literature regarding the diagnostic value of SWME as a result of
      different methodologies. To maximize the diagnostic value of SWME, a three site
      test involving the plantar aspects of the great toe, the third metatarsal, and
      the fifth metatarsals should be used. Screening is vital in identifying DPN
      early, enabling earlier intervention and management to reduce the risk of
      ulceration and lower extremity amputation.

PMID- 19595542
TI  - Effect of temporary shunting on extremity vascular injury: an outcome analysis
      from the Global War on Terror vascular injury initiative.
AB  - OBJECTIVE: Extremity vascular injury during the current war has been defined by
      anecdotal description and case series. These reports focused on estimation of
      short-term limb viability and technical description of commonly used adjuncts.
      Temporary vascular shunting (TVS) has been advocated in current care structures,
      yet mostly due to war environments, broader statistical scrutiny is lacking. This
      study's purpose is to provide perspective on TVS's impact on limb salvage, and
      estimate longer-term freedom from amputation. METHODS: Data from the Joint
      Theater Trauma Registry (JTTR), Balad Vascular Registry (BVR), Walter Reed
      Vascular Registry (WRVR), electronic medical records, and patient interviews were
      collected on American Troops sustaining extremity vascular injury from June 2003
      through December 2007. Those in whom arterial TVS utilization was identified
      comprise the TVS group. These were compared with controls with similar injury
      date and anatomic location managed without TVS. Descriptive statistics were
      employed establishing overall univariate predictors of amputation and comparison
      between groups. Proportional-hazards modeling, with propensity score adjustment
      for systemic injury severity and Level 2 care, characterized risk factors of limb
      loss and effect of TVS. Freedom from amputation was estimated using Kaplan Meier
      log-rank methods. RESULTS: Cases and controls consisted of 64 and 61 extremity
      arterial injuries, respectively. Mean follow-up was 22 months (range: 1-54
      months). The TVS group was more severely injured (mean injury severity score
      [ISS]: 18 [SD = 10] TVS vs. 15 [SD = 10] control, P = .05) and more likely to
      receive Level 2 care (TVS: 26%; control: 10%, P = .02). Overall, a total of 26
      amputations occurred (21%). Penetrating blasts, compared with gunshot wounds,
      were associated with amputation (30% vs. 6%, P = .002). After propensity score
      adjustment, use of TVS suggested a reduced risk of amputation (relative risk [RR]
      = 0.47; 95% confidence interval [CI] [0.18-1.19]; P = .11). Venous repair was
      associated with limb salvage (RR = 0.2; 95% CI [0.04-0.99], P = .05). Associated
      fracture (RR = 5.0; 95% CI [1.45-17.28], P = .01), and elevated mangled extremity
      severity score (MESS) ([MESS 5-7] RR = 3.5, 95% CI [0.97-12.36], P = .06; [MESS 8
      12] RR = 16.4; 95% CI (3.79-70.79), P < .001) predicted amputation. Amputation
      free survival was 78% in the TVS group and 77% in the control group at three
      years (P = .5). CONCLUSION: Temporary vascular shunting used as a damage control
      adjunct in management of wartime extremity vascular injury does not lead to worse
      outcomes. Benefit from TVS is suggested, but not statistically significant.
      Injury specific variables of venous ligation, associated fracture, and
      penetrating blast mechanism are associated with amputation. Amputation-free
      survival after vascular injury in Operation Iraqi Freedom is 79% at three years.
      Further studies to statistically define any possible benefits of TVS are needed.

PMID- 19595544
TI  - Iatrogenic injuries of the common femoral artery (CFA) and external iliac artery
      (EIA) during endograft placement: an underdiagnosed entity.
AB  - OBJECTIVE: Early limb occlusions following endovascular treatment of aorto-iliac
      aneurysmal disease is not uncommon (4%-13%). To assess whether the femoral artery
      entry site could potentially cause this complication, we prospectively evaluated
      the ipsilateral common femoral artery (CFA) and distal external iliac artery
      (EIA) with intraoperative duplex scans (IDS). METHODS: There were 134 patients
      with infrarenal nonruptured abdominal aorto-iliac aneurysms treated with
      endografts since 2002 at our institution. Age ranged from 65 to 89 years (mean:
      77 +/- 7 years). Aneuryx (n = 41), Zenith (n = 50), and Excluder (n = 43)
      endografts were used for repair. All procedures were performed via open exposure
      of the CFA. Introducer diameter varied from 12 mm to 22 mm. All patients
      underwent IDS of the CFA and distal EIA after repair of the arteriotomies.
      RESULTS: In 34 patients (25%), we documented intimal dissections causing severe
      (>70%) stenoses. Of the 271 arteries that were examined, 38 (14%) had abnormal
      findings that demanded intervention. These were repaired with flap excision,
      tacking sutures revision, or patch angioplasty (n = 36). Repeat IDS confirmed the
      adequacy of the repair. No statistical difference was noted if the site of larger
      introducer sheath and the incidence of flap formation. In addition, 10 small
      flaps or plaques were visualized but did not create significant stenosis. No
      differences were noted in the incidence of positive duplex exams between each
      type graft (P = .4). No early or late iliac limb occlusions were noted. Follow-up
      of 94% was obtained. CONCLUSIONS: Completion arterial duplex scans are helpful in
      detecting a substantial number of clinically unsuspected technical defects caused
      by introducer sheaths. Timely diagnosis and repair of these defects may decrease
      the incidence of early limb occlusion following endograft placement.

PMID- 19595545
TI  - The correlation of aortic neck length to early and late outcomes in endovascular
      aneurysm repair patients.
AB  - BACKGROUND: Initially, patients with a short angulated aortic neck were
      considered unfit for endovascular aneurysm repair (EVAR). Recently, however, more
      liberal use of EVAR has been advocated. This study analyzes the correlation of
      aortic neck length to early and late outcomes. METHODS: We analyzed 238 patients
      who underwent EVAR during a recent 7-year period. All patients were followed up
      clinically and underwent postoperative duplex ultrasound imaging or computed
      tomography angiography, which were repeated every 6 months. Aortic neck length
      was classified into >or=15 mm (L1, n = 195), 10 to <15 mm (L2, n = 24), and <10
      mm (L3, n = 17). Kaplan-Meier methods were used to estimate freedom from late
      endoleak, early and late reintervention, and survival. RESULTS: Analyzed were 49
      Ancure, 47 AneuRx, 104 Excluder, and 38 Zenith grafts. The mean follow-up was
      24.7 months (range, 1-87 months). The initial technical success was 99%. The
      perioperative complication rates for groups L1, L2, and L3 were 13%, 21%, and
      24%, respectively (P = .289). Proximal type I early endoleaks occurred in 12%,
      42%, and 53% in groups L1, L2, and L3, respectively (P < .001). Intraoperative
      proximal aortic cuffs were needed to seal proximal type I endoleaks in 10%, 38%,
      and 47% in L1, L2, and L3 groups, respectively (P < .0001). However, the rate of
      late reintervention was comparable in all groups. Postoperatively, the size of
      the abdominal aortic aneurysm decreased or remained unchanged in 95%, 94%, and
      88% in L1, L2, and L3, respectively (P = .660). Rates of freedom from late type I
      endoleak at 1, 2, and 3 years were 84%, 82%, and 80% for L1; 68%, 54%, and 54%
      for L2; and 71%, 71%, and 53% for L3 (P = .0263). Rates of freedom from late
      intervention at 1, 2, and 3 years were 96%, 94%, and 92% for L1; and 94%, 83%,
      and 83% for L2; and 93%, 93%, and 93% for L3 (P = .5334). CONCLUSIONS: EVAR can
      be used for patients with a short aortic neck; however, it was associated with a
      significantly higher rate of early and late type I endoleaks, resulting in an
      increased use of proximal aortic cuffs for sealing the endoleaks.

PMID- 19595546
TI  - Corkscrew external iliac artery.

PMID- 19595547
TI  - Femoropopliteal prosthetic bypass graft infection due to Mycobacterium abscessus
      localized by FDG-PET/CT scan.
AB  - A patient with postvascular graft placement presented with bacteremia but no
      localizing symptoms. Our standard infected graft workup of computed tomography
      (CT) scan, ultrasound scan, magnetic resonance imaging (MRI) scan, and additional
      laboratory tests did not localize the infection source. Nuclear medicine had
      three options including white blood cell (WBC) scan, gallium scan, and the
      fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan.
      FDG-PET/CT imaging alone demonstrated the location. We present an unusual case of
      Mycobacterium abscessus in a vascular graft not localized with CT scan,
      ultrasound scan, or MRI scan and could only be localized with FDG-PET/CT scan.

PMID- 19595548
TI  - Thoracoabdominal and coronary arterial aneurysms in a young man with a history of
      Kawasaki disease.
AB  - We report a case of a large symptomatic thoracoabdominal aortic aneurysm in a 22
      year-old man with a history of Kawasaki disease in childhood. According to
      multislice computed tomography scan findings, the aneurysm was classified as
      Crawford type III. Coronary angiography revealed a giant aneurysm of the left
      coronary artery and aneurysm of the circumflex artery. Functional tests for
      myocardial perfusion and function revealed no significant ischemic territories.
      Because of symptoms of imminent rupture, aneurysm resection and aortic
      reconstruction with a 26-mm zero porosity Dacron graft was performed and was
      successful. Cardiovascular consequences of Kawasaki disease are discussed with
      attention to the late sequelae. Indications for surgical treatment and importance
      of follow-up into adulthood are emphasized.

PMID- 19595549
TI  - Persistent reflux below the knee after stripping of the great saphenous vein.
AB  - OBJECTIVES: This prospective study investigated persistent reflux of the below
      knee great saphenous knee (GSV) 2 years after stripping the above knee GSV and
      the effect on reflux of postoperative incompetent perforating veins (IPVs).
      METHODS: Included were 59 consecutive ambulatory patients in a community hospital
      with untreated primary varicose veins and reflux of the saphenofemoral junction
      and at least the GSV in the upper leg. Patients underwent a preoperative clinical
      examination and color flow duplex ultrasound imaging. Postoperative evaluations
      were at 6 months and 2 years, and 67 limbs were re-evaluable. This analysis was
      adjusted for age, CEAP, follow-up period, and preoperative reflux using a
      multivariate logistic regression model. The difference in diameter of the GSV
      below the knee before and after surgery was measured and tested with the paired t
      test. RESULTS: Clearly visible varicose veins in the GSV below the knee were seen
      in 49 limbs (73%) before surgery and after surgery in 11 limbs (16%) at 6 months
      and in 15 limbs (22%) at 2 years. Reflux in the below knee main stem increased
      from 81% before surgery to 84% at 6 months and 91% at 2 years after surgery.
      Reflux in the posterior calf tributary of the GSV decreased from 67% before
      surgery to 64% at 6 months and 59% at 2 years after surgery. The mean diameter of
      the below knee GSV main stem decreased from 4.7 mm before surgery to 3.3 mm 6
      months after surgery (P < .001), but increased to 3.6 mm 2 years after surgery (P
      < .05). The mean diameter of the posterior calf tributary of the GSV decreased
      from 3.5 mm before surgery to 2.7 mm at 6 months (P < .001), but increased to 2.9
      mm at 2 years (P < .05). Univariate and multivariate logistic regression shows no
      association between reflux in one of the GSV below knee branches and
      postoperative IPVs. CONCLUSION: Many patients (91%) that undergo a short
      stripping procedure will have a persistent reflux of the remnant below knee GSV
      tributaries postoperatively. This incompetence of the distal GSV is independent
      from the proximal GSV as well from insufficient perforating veins. There seems to
      be a tendency to worsening of the clinical signs and symptoms between 6 months
      and 2 years after surgery, and this goes along with an increase of reflux and
      diameters of the GSV below knee remnants.

PMID- 19595550
TI  - Duplex-guided balloon angioplasty of failing or nonmaturing arterio-venous
      fistulae for hemodialysis: a new office-based procedure.
AB  - OBJECTIVE: Unquestionably, the federal government has created financial
      incentives for vascular interventionists to perform procedures in their offices
      rather than in a hospital setting. While office venous ablations have been widely
      embraced by the vascular community, those involving the arterial system have not.
      One important reason may be related to the cost of the fluoroscopic equipment.
      Herein, we report on 32 office-based duplex scan-guided balloon angioplasty cases
      for failing or nonmaturing arteriovenous (AV) access. PATIENTS AND METHODS:
      Twenty-five patients (14 males; 11 females; mean age 65.1 +/- 9.11) with chronic
      renal insufficiency underwent 32 office-based ultrasound scan-guided balloon
      angioplasties of their autologous AV fistulas. Twenty-seven procedures were
      performed in fistulas that did not mature while the remaining five were performed
      in failing AV accesses. The indications for these procedures were severe stenoses
      (>70%) as measured by color duplex scan and confirmed by peak systolic velocity
      (PSV) step-up >3. Preoperative duplex scan-derived mean volume flows (VFs) and
      highest stenotic PSV were recorded and compared with postoperative findings.
      Access site puncture and cannulation with short sheath, wire, and balloon
      advancement and inflation were guided by duplex scan only. A comparison of
      revenue for hospital-based vs office-based procedures was performed. RESULTS: All
      procedures were successfully completed without fluoroscopy and contrast material.
      There were no systemic complications. One patient (3%) developed an arm hematoma
      due to focal vein rupture which was controlled by a hand compression for 20
      minutes. An additional patient (3%) had a focal intraluminal dissection not
      obstructing the flow. Comparison of preoperative mean VF (350 +/- 180 mL/minute)
      and postoperative mean VF (933 +/- 332 mL/minute) demonstrated a statistically
      significant increase with P < .0001. Preoperative mean PSV 582 +/- 923 cm/second
      decreased to postoperative 1 mean PSV 244 +/- 97 cm/second (P < .0001). After
      deduction of procedure-related expenses ($730/case) from the global fee, the net
      income from these 32 cases totaled $51,746, making the return 4.32 times higher
      than that of the hospital setting (potential professional fee for the same cases 
      $11,983). CONCLUSION: This early experience suggests that office-based
      endovascular repair of AV access under duplex scan-guidance is feasible and safe.
      The superficial location of AV access facilitates duplex scan visualization. This
      proposed approach averts contrast material use and radiation exposure. Finally,
      it appears to be financially more lucrative than the same hospital-based
      procedures.

PMID- 19595551
TI  - In search of optimal compression therapy for venous leg ulcers: a meta-analysis
      of studies comparing diverse [corrected] bandages with specifically designed
      stockings.
AB  - OBJECTIVE: In search of an optimal compression therapy for venous leg ulcers, a
      systematic review and meta-analysis was performed of randomized controlled trials
      (RCT) comparing compression systems based on stockings (MCS) with divers
      bandages. METHODS: RCT were retrieved from six sources and reviewed
      independently. The primary endpoint, completion of healing within a defined time
      frame, and the secondary endpoints, time to healing, and pain were entered into a
      meta-analysis using the tools of the Cochrane Collaboration. Additional
      subjective endpoints were summarized. RESULTS: Eight RCT (published 1985-2008)
      fulfilled the predefined criteria. Data presentation was adequate and showed
      moderate heterogeneity. The studies included 692 patients (21-178/study, mean age
      61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9
      years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks.
      Patient and ulcer characteristics were evenly distributed in three studies,
      favored the stocking groups in four, and the bandage group in one. Data on the
      pressure exerted by stockings and bandages were reported in seven and two
      studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of
      ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P <
      .00001). The average time to healing (seven studies, 535 patients) was 3 weeks
      shorter with stockings (P = .0002). In no study performed bandages better than
      MCS. Pain was assessed in three studies (219 patients) revealing an important
      advantage of stockings (P < .0001). Other subjective parameters and issues of
      nursing revealed an advantage of MCS as well. CONCLUSIONS: Leg compression with
      stockings is clearly better than compression with bandages, has a positive impact
      on pain, and is easier to use.

PMID- 19595552
TI  - Endovascular repair of blunt thoracic aortic injury: techniques and tips.

PMID- 19595553
TI  - Isolated limb perfusion with tissue plasminogen activator for acute hand
      ischemia.
AB  - A 62-year old woman presented with an ischemic hand postoperatively from an open
      abdominal aortic aneurysm repair. Traditional open embolectomy techniques were
      attempted but failed < or = 24 hours. She was then taken for isolated limb
      perfusion with tissue plasminogen activator for ongoing ischemia of the hand. A
      satisfactory technical result was achieved, and the patient remains with a
      functional extremity.

PMID- 19595554
TI  - Neighborhood safety, socioeconomic status, and physical activity in older adults.
AB  - BACKGROUND: Neighborhood environment can have a substantial influence on the
      level of physical activity among older adults. Yet, the moderating influence of
      various measures of SES on the association between perceived neighborhood safety
      and leisure-time physical activity (LTPA) among older adults remains unknown.
      PURPOSE: The study was designed to investigate the association between perceived
      neighborhood safety and LTPA in a nationally representative sample of older
      adults, and to evaluate SES characteristics as potential effect modifiers in the
      association between perceived neighborhood safety and LTPA. METHODS: Cross
      sectional data from the 2004 Health and Retirement Study of older adults aged
      >or=50 years were used to examine the association between perceived neighborhood
      safety and LTPA. Differences in LTPA were evaluated across three measures of SES:
      education, household income, and household wealth. SES was also evaluated as a
      potential effect modifier in the association between perceived neighborhood
      safety and LTPA. The analysis was conducted in 2008. RESULTS: An SES gradient in
      LTPA was noted across measures of SES used in this study. After controlling for
      SES and demographic characteristics and functional limitations, older adults who
      perceived their neighborhood as safe had an 8% higher mean rate of LTPA compared
      to older adults who perceived their neighborhood as unsafe. The association was
      no longer significant when self-rated health was added. Additionally, SES was not
      a significant effect modifier in the association between perceived neighborhood
      safety and LTPA. CONCLUSIONS: SES, demographic characteristics, and functional
      limitations substantially attenuated the positive association between perceived
      neighborhood safety and LTPA; however, with the inclusion of self-rated health,
      the association was no longer present. This finding suggests that self-rated
      health may mediate this association. The lack of significance in the interaction
      between perceived neighborhood safety and SES suggests that prevention efforts to
      increase physical activity among older adults should consider perceptions of
      neighborhood safety as a potential barrier regardless of SES.

PMID- 19595555
TI  - Trends in unintentional injury deaths, U.S., 1999-2005: age, gender, and
      racial/ethnic differences.
AB  - BACKGROUND: The details hidden within the recent increase (1999-2004) in
      unintentional injury mortality have not been studied. PURPOSE: The objectives
      were to analyze the trends in mortality rates from unintentional injuries from
      1999 to 2005 and identify changes in rates for specific population subgroups.
      METHODS: Mortality data came from the CDC's Web-based Injury Statistics Query and
      Reporting System. Trends during 1999-2005 were analyzed by cause, gender, race,
      age group, and state separately. Annual percent changes in rates and linear
      regression were used to measure the increase from 1999 to 2005 and examine its
      significance. The data were analyzed in 2008. RESULTS: Overall unintentional
      injury mortality in the U.S. increased by 1.8/100,000 per year from 1999 to 2005,
      rising from 35.3/100,000 in 1999 to 39.0 in 2005. Total unintentional injury
      mortality increased significantly in whites only, a 2% increase per year for
      white men/boys and a 2.8% increase for white women/girls (p<0.05). Poisoning
      mortality increased significantly in adults of all racial groups. Subgroup
      analyses revealed that the increases in total unintentional injury mortality
      among whites were mainly the result of increases in falls in adults aged >or=45
      years and poisoning in people aged 15-64 years. Large state-specific differences
      in trends were observed for these two causes. In addition, the increases in death
      rates from unintentional suffocation in white children aged <5 years, motor
      vehicle crashes in whites aged 45-64 years, and drowning and fire/burns in white
      women aged 45-54 years were large and significant (p<0.05). CONCLUSIONS: Specific
      subgroups of whites have recently experienced the most marked increases in fatal
      unintentional injuries, including falls, poisoning, motor-vehicle crashes,
      suffocation, fire/burns, and drowning. These increases merit further attention
      from researchers and policymakers.

PMID- 19595556
TI  - Disaster preparedness of households with special needs in southeastern
      Pennsylvania.
AB  - BACKGROUND: Individuals with disabilities are disproportionately vulnerable in
      evacuation emergencies, and they face numerous challenges accessing resources for
      response and recovery. PURPOSE: The aim of this study was to compare the
      preparedness behaviors of households with and without special-needs members.
      METHODS: A random-digit-dial telephone survey was conducted of 501 adults in
      southeastern Pennsylvania in 2008. The survey instrument gathered data on
      sociodemographic characteristics, disability status/functional limitations, and
      preparedness behaviors related to an evacuation emergency. Analyses were
      conducted in 2009 and included multiple logistic regressions. Data were weighted
      to correct for unequal probabilities of selection and response. RESULTS: Nineteen
      percent (n=95) of respondents reported living in a household in which someone had
      a transportation-related special need requiring assistance in case of an
      emergency. Households with a special-needs member had greater odds of having
      arranged a place to meet (OR=2.2; 95% CI=1.26, 3.88); located a shelter (OR=1.8;
      95% CI=1.05, 3.24); or packed a bag (OR=1.8; 95% CI=1.02, 3.21). No significant
      differences were identified with respect to awareness of evacuation routes,
      purchasing of food and water, or creation of an emergency plan to guide
      evacuation decision-making. CONCLUSIONS: Despite both greater vulnerability to
      disaster and numerous messages by governmental and nongovernmental organizations,
      households with special-needs members are not more likely to engage in time
      consuming preparedness behaviors such as planning and buying. Understanding the
      motivations and behaviors of special-needs groups is critical to designing
      informed risk-communication messages and interventions to bolster the
      preparedness of the most vulnerable populations.

PMID- 19595558
TI  - Peridomestic Lyme disease prevention: results of a population-based case-control
      study.
AB  - BACKGROUND: Peridomestic Lyme disease-prevention initiatives promote personal
      protection, landscape modification, and chemical control. PURPOSE: A 32-month
      prospective age- and neighborhood-matched case-control study was conducted in
      Connecticut to evaluate the effects of peridomestic prevention measures on risk
      of Lyme disease. METHODS: The study was conducted in 24 disease-endemic
      Connecticut communities from 2005 to 2007. Subjects were interviewed by telephone
      using a questionnaire designed to elicit disease-prevention measures during the
      month prior to the case onset of erythema migrans. Data were analyzed in 2008 by
      conditional logistic regression. Potential confounders, such as
      occupational/recreational exposures, were examined. RESULTS: Between April 2005
      and November 2007, interviews were conducted with 364 participants with Lyme
      disease, and 349 (96%) were matched with a suitable control. Checking for ticks
      within 36 hours of spending time in the yard at home was protective against Lyme
      disease (OR=0.55; 95% CI=0.32, 0.94). Bathing within 2 hours after spending time
      in the yard was also protective (OR=0.42; 95% CI=0.23, 0.78). Fencing of any type
      or height in the yard, whether it was contiguous or not, was protective (OR=0.54;
      95% CI=0.33, 0.90). No other landscape modifications or features were
      significantly protective against Lyme disease. CONCLUSIONS: The results of this
      study suggest that practical activities such as checking for ticks and bathing
      after spending time in the yard may reduce the risk of Lyme disease in regions
      where peridomestic risk is high. Fencing did appear to protect against infection,
      but the mechanism of its protection is unclear.

PMID- 19595557
TI  - Active Mothers Postpartum: a randomized controlled weight-loss intervention
      trial.
AB  - BACKGROUND: Pregnancy may contribute to overweight and obesity. PURPOSE: The
      primary objective of Active Mothers Postpartum was to promote a reduction in BMI
      through 24-months postpartum via sustainable lifestyle changes. DESIGN:
      Behavioral intervention RCT to enhance postpartum weight loss.
      SETTING/PARTICIPANTS: A total of 450 overweight or obese women, enrolled 6-weeks
      postpartum, were recruited through obstetrics clinics and community posters in
      the Durham NC area. INTERVENTION: Intervention participants were offered eight
      healthy-eating classes, ten physical-activity classes, and six telephone
      counseling sessions over 9 months. MAIN OUTCOME MEASURES: Changes from baseline
      (6-weeks postpartum) to 1-month post-intervention (12-months postpartum) in: (1)
      diet (caloric intake, calories from fat, intake of certain foods); (2) physical
      activity (self-reported physical activity, television time); and (3) weight
      (collected 2004-2007, analyzed 2007-2008). RESULTS: Mean weight loss was 0.90 kg
      (+/-5.1 kg) in the intervention group and 0.36 kg (+/-4.9 kg) in the control
      group; this difference was not significant. There were also no significant group
      differences in improvement of diet or increased physical activity. In secondary
      analyses, there was a positive bivariate relationship between classes attended
      and weight loss (p=0.01). CONCLUSIONS: There were no significant differences
      among the arms in diet, physical activity, or weight change. Home-based
      interventions via mail, telephone, or Internet/e-mail may be more feasible and
      successful in this population. The postpartum period is an important phase in
      women's lives with regard to weight retention, but engaging them during this busy
      period remains a challenge. TRIAL REGISTRATION: NCT00212251.

PMID- 19595560
TI  - Usefulness of pulse oximetry using the SET technology in critically ill adult
      patients.
AB  - BACKGROUND: Pulse oximeters are routinely used in severely ill patients to detect
      hypoxemia early. In various clinical situations, however, conventional devices
      may be unable to display valid values or any value whatsoever. The usefulness of
      the Signal Extraction Technology (SET) in these situations has not yet been
      investigated. METHOD: Twenty-five adult patients requiring norepinephrine,
      regardless of the reason or dosage, or having a defective signal with a
      conventional oximeter were equipped with both their conventional saturation
      sensor (Oxymax Nellcor) and a SET saturation sensor (Masimo) connected to its
      monitor. Saturation values displayed by each pulse oximeter and the SaO(2)
      measured concomitantly by cooximetry were gathered on inclusion and then whenever
      one of the two sensors did not display a value, or when the difference between
      the values was greater than five saturation points, or at any time a blood gas
      analysis was done. RESULTS: During the study period, 83 measures were collected.
      Using the Bland and Altman method, SaO(2) estimates by the SET system were more
      accurate than those by the conventional system (bias+/-2 S.D. of 0.0%+/-3.1% vs
      2.1%+/-11.0%, respectively), even when only valid values (values accompanied by a
      satisfactory quality index) were considered (0.0%+/-2.7% vs 1.2%+/-7.0%).
      CONCLUSIONS: In situations at risk of producing defective signals when using
      conventional sensors, the SET system provided more valid SaO(2) estimates.

PMID- 19595559
TI  - Contribution of athletic identity to child and adolescent physical activity.
AB  - BACKGROUND: Identity theorists maintain that domain-specific self-concepts help
      explain the differential investment of people's time and effort in various
      activities. PURPOSE: This study examined the contribution of athletic identity
      and three key demographic variables to physical activity and sports team
      participation. METHODS: Students in Grades 4-5 (n=391, mean age 9.9 years, range
      8-13 years, collected in 2003) and Grades 7-8 (n=948, mean age 13.6 years, range
      11-15 years, collected in 2002 and 2006) completed the 40-item Athletic Identity
      Questionnaire, which measures self-perceptions of athletic appearance;
      competence; importance of physical activity and sports; and encouragement for
      activity from parents, teachers, and friends. Hierarchic multiple regression
      analyses in 2008 assessed the effects of athletic identity, race/ethnicity group,
      gender, and overweight status on 7-day moderate-to-vigorous physical activity
      (MVPA) and organized sport team participation in each age group. RESULTS: In
      children and adolescents, the global score of athletic identity was
      independently, positively related to MVPA (p<0.0001, p<0.0001, respectively) and
      team participation (p<0.0001, p<0.0001, respectively), after controlling for
      demographic variables. More variance in MVPA was explained in children (23%) than
      in adolescents (5%), in contrast to team sports (5% in children, 15% in
      adolescents). In the subscale analyses, positive relationships for appearance,
      competence, importance, and parental encouragement persisted independent of
      demographic factors. CONCLUSIONS: Results support the role of athletic self
      concept in promoting physical activity and organized sport participation in
      children and adolescents.

PMID- 19595561
TI  - Prevalence of anxiety disorders among adults seeking speech therapy for
      stuttering.
AB  - The present study explored the prevalence of anxiety disorders among adults
      seeking speech therapy for stuttering. Employing a matched case-control design,
      participants included 92 adults seeking treatment for stuttering, and 920 age-
      and gender-matched controls from the Australian National Survey of Mental Health
      and Well-being. A conditional logistic regression model was used to estimate odds
      ratios for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV) and International Classification of Diseases (ICD-10) anxiety disorders.
      Compared with matched controls, the stuttering group had six- to seven-fold
      increased odds of meeting a 12-month diagnosis of any DSM-IV or ICD-10 anxiety
      disorder. In terms of 12-month prevalence, they also had 16- to 34-fold increased
      odds of meeting criteria for DSM-IV or ICD-10 social phobia, four-fold increased
      odds of meeting criteria for DSM-IV generalized anxiety disorder, and six-fold
      increased odds of meeting criteria for ICD-10 panic disorder. Overall, stuttering
      appears to be associated with a dramatically heightened risk of a range of
      anxiety disorders.

PMID- 19595563
TI  - Closed quotient and spectral measures of female adolescent singers in different
      singing styles.
AB  - Although quantifiable assessment of the singing voice is now commonplace,
      research on young (child and adolescent) voices is still in its infancy. There is
      still insufficient data on young people's voices based on which, "norms" in
      behavior could be modeled, particularly for contemporary commercial music (CCM),
      such as musical theater (MT). The objective of this study was to assess if
      quantifiable differences in vocal production and acoustic output of young singers
      exist between "classical" and "MT" styles. The study was a prospective cohort
      study of 20 adolescent female singers aged 12-17 years training their voices
      using a system, which includes both "classical" and "MT" styles. The study
      examined laryngographically derived closed quotient (CQ), average vowel spectra
      (AVS) and long-term average spectra (LTAS) measures of the sung voices of singers
      in "classical" and "MT" styles. The spectral slope was shallower for the MT
      voice, and the mean CQ was significantly higher across the pitch range when
      singing in an MT style than in a "classical" style. The second to fifth harmonics
      were stronger in the MT style than in classical, with a significant difference
      between the two styles. The increase in relative intensity in the first five
      harmonics was disproportionately higher than the increase in CQ. Results,
      therefore, suggested that MT singing primarily uses change in resonance strategy
      rather than raised vocal tension to achieve the tonal changes associated with the
      genre.

PMID- 19595562
TI  - Measuring the quality of life of people with profound multiple disabilities using
      the QOL-PMD: first results.
AB  - The present study focused on the objective components of quality of life (QOL) of
      people with profound multiple disabilities (PMD). More specific, we aimed at
      evaluating different dimensions of QOL of people with PMD and investigating the
      association between their QOL and several personal (age, gender, intellectual
      capabilities, motor limitations, sensory limitations, physical and mental health
      status) as well as setting characteristics (location of the setting, type of
      setting, size of the setting, group size, group composition, staffing level and
      staff turnover). As a measure of the QOL of people with PMD we used the QOL-PMD,
      a questionnaire that we specifically developed for this purpose. To measure the
      personal and setting characteristics we also used a self-developed questionnaire.
      Forty-nine people with PMD were selected. For each of these people three
      informants were chosen who each filled out the QOL-PMD. To account for the
      clustered nature of the data, data were analysed by means of mixed models.
      Characteristics regarding the medical condition of the person with PMD turned out
      to be most strongly associated with the QOL-PMD scores. Other personal
      characteristics such as age, gender, motor limitations and sensory limitations
      did not have a significant effect on the QOL-PMD scores. With regard to the
      setting characteristics, location of the setting and staffing level turned out to
      have a significant effect on the QOL-PMD scores.

PMID- 19595564
TI  - New passivity criteria for neural networks with time-varying delay.
AB  - In this paper, improved criteria for the passivity of neural networks with time
      delay are proposed. The improvement is achieved by exploiting the finer
      relationships between the time-varying delay and its size bound which allow the
      use of more slack variables. It is illustrated via numerical examples that the
      proposed results are less conservative than those available in the literature.

PMID- 19595565
TI  - Chaotic phase synchronization and desynchronization in an oscillator network for
      object selection.
AB  - Object selection refers to the mechanism of extracting objects of interest while
      ignoring other objects and background in a given visual scene. It is a
      fundamental issue for many computer vision and image analysis techniques and it
      is still a challenging task to artificial visual systems. Chaotic phase
      synchronization takes place in cases involving almost identical dynamical systems
      and it means that the phase difference between the systems is kept bounded over
      the time, while their amplitudes remain chaotic and may be uncorrelated. Instead
      of complete synchronization, phase synchronization is believed to be a mechanism
      for neural integration in brain. In this paper, an object selection model is
      proposed. Oscillators in the network representing the salient object in a given
      scene are phase synchronized, while no phase synchronization occurs for
      background objects. In this way, the salient object can be extracted. In this
      model, a shift mechanism is also introduced to change attention from one object
      to another. Computer simulations show that the model produces some results
      similar to those observed in natural vision systems.

PMID- 19595566
TI  - Extending the Evolutionary Robotics approach to flying machines: an application
      to MAV teams.
AB  - The work presented in this article focuses on the use of embodied neural networks
      -developed through Evolutionary Robotics and Multi-Agent Systems methodologies-
      as autonomous distributed controllers for Micro-unmanned Aerial Vehicle (MAV)
      teams. The main aim of the research is to extend the range of domains that could
      be successfully tackled by the Evolutionary Robotics approach. The flying robots
      realm is an area that has not been yet thoroughly investigated by this
      discipline. This is due to the lack of an affordable and reliable robotic
      platform to use for carrying out experiments, and to the difficulty and the high
      computational load involved in experiments based upon a realistic software
      simulator for aircraft. We believe that the most recent improvements to the state
      of the art now permit the investigation of this domain. For demonstrating this
      point, two different evolutionary computer simulation models are presented in
      this article. The first model, which uses a simplified 2D test environment, has
      resulted in controllers evolved with the following capabilities: (1) navigation
      through unknown environments, (2) obstacle-avoidance, (3) tracking of a movable
      target, and (4) execution of cooperative and coordinated behaviors based on
      implicit communication strategies. In order to improve the robustness of these
      results and their potential use in real MAV teams, a more sophisticated 3D model
      is presented herein. The results obtained so far using the two models demonstrate
      the feasibility of the chosen approach for further research on the design of
      autonomous controllers for MAVs.

PMID- 19595567
TI  - An artificial chaotic spiking neuron inspired by spiral ganglion cell: paralleled
      spike encoding, theoretical analysis, and electronic circuit implementation.
AB  - A novel chaotic spiking neuron is presented and its nonlinear dynamics and
      encoding functions are analyzed. A set of paralleled N neurons accepts a common
      analog input and outputs a set of N chaotic spike-trains. Three theorems which
      guarantee that the neurons can encode the analog input into a summation of the N
      chaotic spike-trains are derived: (1) a spike histogram of the summed spike-train
      can mimic waveforms of various inputs, (2) the spike-trains do not synchronize to
      each other and thus the summed spike-train can have N times higher encoding
      resolution than each single spike-train, and (3) firing rates of the neurons can
      be adjusted by internal parameters. The theorems are proven by using nonlinear
      iterative maps and are confirmed by numerical simulations as well. Electronic
      circuit implementation methods of the paralleled neurons are also presented and
      typical paralleled encoding functions are confirmed by both experimental
      measurements and SPICE simulations.

PMID- 19595568
TI  - Case management poststroke did not induce response shift: the value of residuals.
AB  - OBJECTIVES: To estimate the extent to which different methods of assessing
      response shift lead to different conclusions about its presence. STUDY DESIGN AND
      SETTING: A reanalysis of a randomized clinical trial involving 190 persons
      poststroke to evaluate the effectiveness of a case management intervention aimed
      at assisting persons with stroke to make the transition from acute care to home.
      RESULTS: Response shift was found to be nondifferential across groups and was
      therefore ruled out as an explanation for why the case management intervention
      showed no impact on patients' perceptions of their health. The results of a then
      test did not show differential recalibration overtime. Factor analysis did not
      support reconceptualization response shift in either group but did find weak
      evidence for reprioritization response shift. An analysis of residuals indicated
      that approximately 50% of study subjects in each group experienced response shift
      that is probably close to reconceptualization. CONCLUSION: A framework for
      assessing response shift was proposed and investigators planning trials of
      interventions targeting patient-reported outcomes should build into the trial
      methods for response shift investigation. In trials of interventions likely to
      induce response shift, before concluding about intervention-induced change,
      response shift should be ruled out by using a combination of design and
      statistical approaches.

PMID- 19595569
TI  - Venous thromboembolism discharge diagnoses in the Danish National Patient
      Registry should be used with caution.
AB  - OBJECTIVE: We validated discharge diagnoses of venous thromboembolism (VTE) in
      the Danish National Patient Registry. STUDY DESIGN AND SETTING: We identified all
      first-time VTE discharge diagnoses in the Danish National Patient Registry among
      participants of the Danish cohort study "Diet, Cancer, and Health", in the period
      from 1994 to 2006. Medical records were retrieved and VTE diagnoses were verified
      by one of the authors using a standard protocol. The positive predictive value
      (PPV) of a discharge diagnosis of VTE was calculated as percent of registry
      diagnoses with the corresponding true diagnosis in the chart among all registry
      diagnoses. RESULTS: We retrieved medical records from 1,100 of 1,135 participants
      (96.9%) registered with a discharge diagnosis of VTE; 626 diagnoses were
      confirmed and 17 were considered probable. The PPV of diagnoses coded at wards
      was 75.0% (95% confidence interval: 71.9, 77.9). Diagnoses from emergency
      departments were not valid. The PPV varied by type of VTE (deep venous thrombosis
      and pulmonary embolism), type of diagnosis (primary or secondary), and sex.
      CONCLUSION: Data on VTE obtained from administrative registries are a valuable
      source of information but should be used with caution in medical research.

PMID- 19595570
TI  - Tests of measurement invariance failed to support the application of the "then
      test".
AB  - OBJECTIVE: The use of then-test (retrospective pre-test) scores has frequently
      been proposed as a solution to potential confounding of change scores because of
      response shift, as it is assumed that then-test and post-test responses are
      provided from the same perspective. However, this assumption has not been
      formally tested using robust quantitative methods. The aim of this study was to
      compare the psychometric performance of then-test/post-test with traditional pre
      test/post-test data and assessing whether the resulting data structures support
      the application of the then-test for evaluations of chronic disease self
      management interventions. STUDY DESIGN AND SETTING: Pre-test, post-test, and then
      test data were collected from 314 participants of self-management courses using
      the Health Education Impact Questionnaire (heiQ). The derived change scores (pre
      test/post-test; then-test/post-test) were examined for their psychometric
      performance using tests of measurement invariance. RESULTS: Few questionnaire
      items were noninvariant across pre-test/post-test, with four items identified and
      requiring removal to enable an unbiased comparison of factor means. In contrast,
      12 items were identified and required removal in then-test/post-test data to
      avoid biased change score estimates. CONCLUSION: Traditional pre-test/post-test
      data appear to be robust with little indication of response shift. In contrast,
      the weaker psychometric performance of then-test/post-test data suggests
      psychometric flaws that may be the result of implicit theory of change, social
      desirability, and recall bias.

PMID- 19595571
TI  - Applications of health-related quality of life for guiding health care: advances
      in response shift research.

PMID- 19595572
TI  - Systematic review of cross-cultural adaptations of McGill Pain Questionnaire
      reveals a paucity of clinimetric testing.
AB  - OBJECTIVES: The objectives of this study were to identify the available cross
      cultural adaptations of the McGill Pain Questionnaire (MPQ), to describe the
      clinimetric testing that has occurred for each adaptation and to evaluate both
      the quality of the adaptation procedures and the clinimetric testing for each
      version. STUDY DESIGN AND SETTING: This study is a systematic review. Searches of
      the MEDLINE, EMBASE, and CINAHL databases were used to identify relevant studies.
      Data on the quality of the adaptation procedures and clinimetric testing were
      extracted using current guidelines. RESULTS: Forty-four different versions of the
      MPQ were identified representing 26 different languages/cultures. Regardless of
      the method of cross-cultural adaptation, clinimetric testing of the adapted
      questionnaires was generally poorly performed and for 18 versions no clinimetric
      testing has been undertaken. CONCLUSIONS: Although the MPQ has been adapted into
      a large number of languages, because of inadequate testing most of the
      adaptations have unknown clinimetric properties. This situation means that users
      should be cautious when interpreting scores from adapted questionnaires.

PMID- 19595573
TI  - Individual patient meta-analysis--rewards and challenges.

PMID- 19595574
TI  - Structural equation modeling of health-related quality-of-life data illustrates
      the measurement and conceptual perspectives on response shift.
AB  - OBJECTIVE: To illustrate different perspectives on response shift with cancer
      patients' health-related quality-of-life (HRQL) data. In measurement perspective,
      the focus is on bias in the measurement of HRQL. In conceptual perspective, the
      focus is on bias in the explanation of HRQL. STUDY DESIGN AND SETTING: Data came
      from a consecutive series of 202 newly diagnosed cancer patients, heterogeneous
      to cancer site, all undergoing surgery. A HRQL questionnaire was administered
      before and after surgery. Using structural equation modeling, biases and response
      shifts in measurement and explanation of HRQL were investigated with respect to
      patient's cancer site, health status, sex, age, optimism, and social comparison.
      RESULTS: Six measurement biases were found, five of which were considered
      response shift. The "general health" (GH) scale appeared most susceptible to
      response shift. For example, GH scores were not fully determined by HRQL but also
      by optimism before surgery and female sex and downward social comparison after
      surgery. Additionally, two explanation biases were found, neither of which were
      considered response shift-before and after surgery the mental component of HRQL
      was not only affected by cancer site and health status but also by optimism and
      downward social comparison. CONCLUSION: Our approach enables the distinction and
      testing of biases and response shifts in the measurement and explanation of HRQL.

PMID- 19595575
TI  - Absolute risk reductions and numbers needed to treat can be obtained from
      adjusted survival models for time-to-event outcomes.
AB  - OBJECTIVE: Cox proportional hazards regression models are frequently used to
      determine the association between exposure and time-to-event outcomes in both
      randomized controlled trials and in observational cohort studies. The resultant
      hazard ratio is a relative measure of effect that provides limited clinical
      information. STUDY DESIGN AND SETTING: A method is described for deriving
      absolute reductions in the risk of an event occurring within a given duration of
      follow-up time from a Cox regression model. The associated number needed to treat
      can be derived from this quantity. The method involves determining the
      probability of the outcome occurring within the specified duration of follow-up
      if each subject in the cohort was treated and if each subject was untreated,
      based on the covariates in the regression model. These probabilities are then
      averaged across the study population to determine the average probability of the
      occurrence of an event within a specific duration of follow-up in the population
      if all subjects were treated and if all subjects were untreated. RESULTS: Risk
      differences and numbers needed to treat. CONCLUSIONS: Absolute measures of
      treatment effect can be derived in prospective studies when Cox regression is
      used to adjust for possible imbalance in prognostically important baseline
      covariates.

PMID- 19595576
TI  - Classification and regression tree uncovered hierarchy of psychosocial
      determinants underlying quality-of-life response shift in HIV/AIDS.
AB  - OBJECTIVES: Rapkin and Schwartz define response shift as otherwise unexplained,
      discrepant change in health-related quality of life (HRQOL) that is associated
      with change in cognitive appraisal. In this article, we demonstrate how a
      recursive partitioning (rpart) regression tree analytic approach may be used to
      explore cognitive changes to gain additional insight into response-shift
      phenomena. STUDY DESIGN AND SETTING: Data are from the "Choices in Care Study,"
      an evaluation of HIV+ Medicaid recipients' experiences and outcomes in care
      (N=394). Cognitive assessment was based on the QOL appraisal battery. HRQOL was
      measured by the SF-36 Health Survey, version 2 (SF-36v2). RESULTS: We used rpart
      to examine 6-month change in SF-36v2 mental composite score as a function of
      changes in appraisal, after controlling for patient characteristics, health
      changes, and intervening events. Rpart identified nine distinct patterns of
      cognitive change, including three associated with negative discrepancies, four
      with positive discrepancies, and two with no discrepancies. CONCLUSION: Rpart
      classification provides a nuanced treatment of response shift. This methodology
      has implications for evaluating programs, guiding decisions, and targeting care.

PMID- 19595577
TI  - AHRQ series paper 5: grading the strength of a body of evidence when comparing
      medical interventions--agency for healthcare research and quality and the
      effective health-care program.
AB  - OBJECTIVE: To establish guidance on grading strength of evidence for the Evidence
      based Practice Center (EPC) program of the U.S. Agency for Healthcare Research
      and Quality. STUDY DESIGN AND SETTING: Authors reviewed authoritative systems for
      grading strength of evidence, identified domains and methods that should be
      considered when grading bodies of evidence in systematic reviews, considered
      public comments on an earlier draft, and discussed the approach with
      representatives of the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) working group. RESULTS: The EPC approach is conceptually
      similar to the GRADE system of evidence rating; it requires assessment of four
      domains: risk of bias, consistency, directness, and precision. Additional domains
      to be used when appropriate include dose-response association, presence of
      confounders that would diminish an observed effect, strength of association, and
      publication bias. Strength of evidence receives a single grade: high, moderate,
      low, or insufficient. We give definitions, examples, mechanisms for scoring
      domains, and an approach for assigning strength of evidence. CONCLUSION: EPCs
      should grade strength of evidence separately for each major outcome and, for
      comparative effectiveness reviews, all major comparisons. We will collaborate
      with the GRADE group to address ongoing challenges in assessing the strength of
      evidence.

PMID- 19595578
TI  - Factors influencing the choice of new generation antipsychotic medication in the
      treatment of patients with schizophrenia.
AB  - OBJECTIVE: This prospective, naturalistic study investigated the factors
      influencing physicians' choice of antipsychotic drug therapy in the treatment of
      patients with schizophrenia. METHOD: 108 in- and outpatients treated at the
      Department of Psychiatry of the Medical University Innsbruck who started
      treatment with a new generation antipsychotic (except clozapine) were included.
      The following factors were investigated: sociodemographic and illness-related
      variables, pretreatment, the reasons for change of treatment (lack of efficacy,
      side effects, non-compliance), side effects of pretreatment and body-mass-index
      (BMI). RESULTS: Sociodemographic and most illness-related variables did not have
      an influence on the physicians' choice of medication. Risperidone was more
      frequently prescribed in patients with severe positive symptoms than amisulpride
      or quetiapine. Rigidity, orthostatic dizziness and gynecomastia during
      pretreatment were frequently associated with starting patients on ziprasidone. In
      patients with diminished sexual desire ziprasidone was preferred over olanzapine.
      Amisulpride was used more commonly than olanzapine if patients had experienced
      weight gain during pretreatment. Moreover, patients who were prescribed
      amisulpride had a significantly higher BMI in comparison to patients who were
      prescribed olanzapine. The reasons for current change of treatment, as well as
      the drug history (total number of antipsychotic drugs prescribed during the
      course of the illness) did not have an influence on the physicians' choice of
      antipsychotic. CONCLUSION: In summary, the data suggest that side effects have a
      larger influence on the choice of antipsychotic than demographic or illness
      related variables, except the severity of positive symptoms.

PMID- 19595580
TI  - Homonuclear dipolar recoupling of half-integer spin quadrupolar nuclei:
      techniques and applications.
AB  - We review recent advances in solid state NMR methodology for recovering
      homonuclear dipolar interactions among half-integer quadrupolar spins undergoing
      sample rotation. Existing dipolar recoupling techniques are contrasted, based on
      (i) the form of their associated dipolar Hamiltonian, (ii) the different
      experimental conditions necessitating their realization and (iii) their roles as
      components in multi-dimensional NMR correlation spectroscopy. Various types of
      structural information accessible from such solid state NMR experimentation is
      reviewed. Promises and limitations of methodologies targeting homonuclear dipolar
      couplings between half-integer spins under high-resolution conditions are
      discussed, with particular focus on the demands set for structural investigations
      of crystalline as well as structurally disordered (amorphous) inorganic network
      materials.

PMID- 19595579
TI  - Brain opioid receptor binding in early abstinence from alcohol dependence and
      relationship to craving: an [11C]diprenorphine PET study.
AB  - The importance of the opioid receptor system in substance dependence is
      increasingly recognised. We used PET with the non-selective tracer
      [11C]diprenorphine to examine opioid receptor binding in early abstinence from
      alcohol dependence and the relationship to craving. We recruited 11 alcohol
      dependent patients and 13 controls. Subjects underwent one [11C]diprenorphine PET
      scan in early abstinence from dependent alcohol use (approximately 2 weeks) and 2
      months later if continuously abstinent. Global and regional [11C]diprenorphine
      volumes of distribution (VD) were increased in alcohol dependent patients
      compared with controls but did not reach significance. We demonstrated a
      correlation between global and regional [11C]diprenorphine VD and craving in
      alcohol dependent patients which persisted in the anterior cingulate cortex into
      extended abstinence. This confirms previous work showing increased opioid
      receptor availability in early abstinence from substances of abuse and
      correlation with craving suggesting that the opioid system plays a fundamental
      role in this phase of addiction.

PMID- 19595581
TI  - Methyl and t-butyl reorientation in an organic molecular solid.
AB  - We have determined the molecular and crystal structure of 4,5-dibromo-2,7-di-t
      butyl-9,9-dimethylxanthene and measured the (1)H spin-lattice relaxation rate
      from 87 to 270K at NMR frequencies of omega/2pi=8.50, 22.5, and 53.0MHz. All
      molecules in the crystal see the same intra and intermolecular environment and
      the repeating unit is half a molecule. We have extended models developed for (1)H
      spin-lattice relaxation resulting from the reorientation of a t-butyl group and
      its constituent methyl groups to include these rotors and the 9-methyl groups.
      The relaxation rate data is well-fitted assuming that the t-butyl groups and all
      three of their constituent methyl groups, as well as the 9-methyl groups all
      reorient with an NMR activation energy of 15.8+/-1.6kJmol(-1) corresponding to a
      barrier of 17.4+/-3.2kJmol(-1). Only intramethyl and intra-t-butyl intermethyl
      spin-spin interactions need be considered. A unique random-motion Debye (or BPP)
      spectral density will not fit the data for any reasonable choice of parameters. A
      distribution of activation energies is required.

PMID- 19595582
TI  - Surface-enhanced oxidation and detection of Sunset Yellow and Tartrazine using
      multi-walled carbon nanotubes film-modified electrode.
AB  - The insoluble multi-walled carbon nanotubes (MWNT) was successfully dispersed
      into water in the presence of hydrophobic surfactant. After that, MWNT film
      coated glassy carbon electrode (GCE) was achieved via dip-coating and evaporating
      water. Owing to huge surface area, high sorption capacity and subtle electronic
      properties, MWNT film exhibits highly efficient accumulation efficiency as well
      as considerable surface enhancement effects to Sunset Yellow and Tartrazine. As a
      result, the oxidation peak currents of Sunset Yellow and Tartrazine remarkably
      increase at the MWNT film-modified GCE. Based on this, a novel electrochemical
      method was developed for the simultaneous determination of Sunset Yellow and
      Tartrazine. The limits of detection are 10.0 ng mL(-1) (2.2 x 10(-8)mol L(-1))
      and 0.1 microg mL(-1) (1.88 x 10(-7)mol L(-1)) for Sunset Yellow and Tartrazine.
      Finally, the proposed method was successfully used to detect Sunset Yellow and
      Tartrazine in soft drinks.

PMID- 19595583
TI  - Bacterial attachment over a wide range of ionic strengths.
AB  - The number of bacterial cells adhered on a glass surface was counted over a wide
      range of ionic strengths. The counted number increased linearly with the square
      root of time. The rate of attachment increased with the increase in ionic
      strength and then plateaued. The rate of attachment was analyzed on the basis of
      the potential barrier between the surface of the bacterial cell and that of the
      substratum. An equation for formulating the dependence of the attachment rate on
      the ionic strength was proposed, which seems to be useful for the systematic
      understanding of bacterial attachment in various environments, from terrestrial
      to marine.

PMID- 19595584
TI  - Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced
      colon carcinogenesis in experimental animals.
AB  - The present study was aimed at evaluating the chemopreventive property of Cynodon
      dactylon. The antioxidant, antiproliferative and apoptotic potentials of the
      plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric
      oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines
      (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo
      chemopreventive property of the plant extract was studied in DMH-induced colon
      carcinogenesis. The methanolic extract of C. dactylon was found to be
      antiproliferative and antioxidative at lower concentrations and induced apoptotic
      cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon
      increased the levels of antioxidant enzymes and reduced the number of dysplastic
      crypts in DMH-induced colon of albino rats. The present investigation revealed
      the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM
      cells and experimentally induced colon carcinogenesis in rats.

PMID- 19595585
TI  - Depletion of selective serotonin reuptake inhibitors during sewage sludge
      composting.
AB  - Sewage and sewage sludge is known to contain pharmaceuticals, and since sewage
      sludge is often used as fertilizer within agriculture, the reduction of the
      selective serotonin reuptake inhibitors (SSRIs) Citalopram, Sertraline,
      Paroxetine, Fluvoxamine and Fluoxetine during composting has been investigated.
      Sewage sludge was spiked with the SSRIs before the composting experiment started,
      and the concentration of the SSRIs in the sludge during a 21 day composting
      period was measured by liquid phase microextraction (LPME) and high-performance
      liquid chromatography-mass spectrometry. All the SSRIs had a significant decrease
      in concentration during the composting process. The highest reduction rates were
      measured for Fluoxetine and Paroxetine and the lowest for Citalopram. In addition
      three out of four known SSRI metabolites were found in all the samples, and two
      of them showed a significant increase in concentration during the composting
      period.

PMID- 19595586
TI  - A novel glucose biosensor based on the immobilization of glucose oxidase onto
      gold nanoparticles-modified Pb nanowires.
AB  - A novel glucose biosensor was developed, based on the immobilization of glucose
      oxidase (GOD) with cross-linking in the matrix of bovine serum albumin (BSA) on a
      Pt electrode, which was modified with gold nanoparticles decorated Pb nanowires
      (GNPs-Pb NWs). Pb nanowires (Pb NWs) were synthesized by an L-cysteine-assisted
      self-assembly route, and then gold nanoparticles (GNPs) were attached onto the
      nanowire surface through -SH-Au specific interaction. The morphological
      characterization of GNPs-Pb NWs was examined by transmission electron microscopy
      (TEM). Cyclic voltammetry and chronoamperometry were used to study and to
      optimize the electrochemical performance of the resulting biosensor. The
      synergistic effect of Pb NWs and GNPs made the biosensor exhibit excellent
      electrocatalytic activity and good response performance to glucose. The effects
      of pH and applied potential on the amperometric response of the biosensor have
      been systemically studied. In pH 7.0, the biosensor showed the sensitivity of
      135.5 microA mM(-1) cm(-2), the detection limit of 2 microM (S/N=3), and the
      response time <5 s with a linear range of 5-2200 microM. Furthermore, the
      biosensor exhibits good reproducibility, long-term stability and relative good
      anti-interference.

PMID- 19595587
TI  - Evaluation of biosensor surfaces for the detection of microtubule perturbation.
AB  - Dual polarization interferometry (DPI) and resonant mirror (RM) methods were used
      to characterize the growth of microtubules (MTs) on biosensor surfaces. The
      structure and dynamics of MTs play an important role in cell division and are a
      target for many anti-cancer drugs. Evidence from DPI demonstrated the growth of
      MTs on streptavidin-biotinylated-tubulin surfaces from the increase in mass and
      thickness, with a simultaneous decrease in density. The initial increase in
      thickness of 0.236 nm/min suggested the elongation of protofilaments before they
      join laterally to form the MT, where the rate of growth increased to 0.436
      nm/min. Continuous mass increases were also observed when tubulin was added to a
      similar underlying RM surface. Tubulin binding to these surfaces was also
      temperature dependent, increasing the absolute response with MT stabilizers,
      while inhibiting binding with destabilizers when temperature was changed from 15
      to 37 degrees C. Finally, the initial rates of tubulin assembly (mean+/-SD, n=3)
      with MT-stabilizer agents were significantly higher at 1.50+/-0.27 and 1.04+/
      0.13 arcseconds/s, respectively, compared to 0.37+/-0.11 arcseconds/s for tubulin
      containing GTP only. In the presence of the MT destabilizers, colchicine and
      dolastatin 10, the slopes of initial rates were lower than in their absence at
      0.05+/-0.01 and 0.27+/-0.08 arcseconds/s, respectively. This provides evidence
      for the ability of surface-based optical sensors to distinguish between MT
      stabilizers and destabilizers, while also paving the path to develop other
      methods to screen for MT-perturbing agents using the same underlying surface
      engineering.

PMID- 19595588
TI  - Biogas production from different substrates in an experimental Continuously
      Stirred Tank Reactor anaerobic digester.
AB  - Different mixtures were digested in a single-stage, batch, mixed, laboratory
      scale mesophilic anaerobic digester at the Biomass Research Centre Laboratory
      (University of Perugia). The yield and the composition of biogas from the
      different substrates were evaluated and the cumulative curves were estimated. Two
      experimental campaigns were carried out, the first on three mixtures (chicken,
      pig and bovine manures), the second on animal and vegetal biomasses (chicken and
      cow manure, olive husk) with different inocula (rumen fluid and digested sludge).
      In the first campaign pig manure mixture showed the maximum biogas production
      (0.35 N m(3)/kg) and energy content (1.35 kWh/kg VS); in the second one the
      differences in produced biogas from the different inocula were analyzed: olive
      husk with piggery manure anaerobically digested as inoculum showed the higher
      biogas (0.28 N m(3)/kg VS) and methane yield (0.11 N m(3)/kg VS), corresponding
      to an energetic content of 1.07 kWh/kg VS. All data obtained from the laboratory
      scale anaerobic digester are comparable to the values in literature for several
      biomass and in particular for olive husk, dairy manure and chicken manure.

PMID- 19595589
TI  - Biocatalytic cascade oxidation using laccase for pyranose 2-oxidase regeneration.
AB  - The interactions between two oxidoreductases coupled by an artificial redox
      mediator have been described quantitatively to increase both stability and
      productivity. In this cascade oxidation, pyranose 2-oxidase oxidizes several
      aldoses at the C-2 position to 2-ketoaldoses. A redox mediator is used as
      electron acceptor for pyranose 2-oxidase because it shows more favourable
      kinetics in comparison to oxygen. The reduced redox mediator is in turn re
      oxidized by laccase, which uses oxygen as the terminal electron acceptor,
      reducing it fully to water. However, pyranose 2-oxidase is capable of using
      oxygen as an electron acceptor in a competing side reaction, leading to the
      formation of hydrogen peroxide, which is detrimental for both enzymes and
      seriously limits the operational stability of both enzymes. The experimental
      results showed full conversion of the aldose to the 2-ketoaldose and a good
      agreement with the simulations of the process.

PMID- 19595590
TI  - Rational design of orally-active, pyrrolidine-based progesterone receptor partial
      agonists.
AB  - Using the X-ray crystal structure of an amide-based progesterone receptor (PR)
      partial agonist bound to the PR ligand binding domain, a novel PR partial agonist
      class containing a pyrrolidine ring was designed. Members of this class of N
      alkylpyrrolidines demonstrate potent and highly selective partial agonism of the
      progesterone receptor, and one of these analogs was shown to be efficacious upon
      oral dosing in the OVX rat model of estrogen opposition.

PMID- 19595591
TI  - Synthesis and opioid receptor activity of indolopropellanes.
AB  - A series of skeletal rearranged indolomorphinans 7a-d were obtained by N
      demethylation of 3-methoxy-N-methyl-14-hydroxymorphinan-6-one 12 followed by N
      realkylation, reduction and Fischer indole cyclization. The structure of the
      novel skeleton was confirmed by X-ray analysis. These new indoles displayed
      moderate binding affinity and selectivity at the mu receptor, with compound 7b
      showing the highest affinity at this receptor with a K(i) value of 40nM, and 6-
      and 25-fold selectivity against delta and kappa receptors, respectively. Function
      assays showed that indolopropellanes 7b and 7c possessed full agonistic activity
      at all the opioid receptors indicating a different interaction model existed.

PMID- 19595592
TI  - Dual task effects for asymmetric stepping on a split-belt treadmill.
AB  - Bilaterally asymmetric stepping during walking is common to a number of
      pathological gaits (e.g., hemiplegia, limping). In the present work, the
      attention level of asymmetric stepping was studied by having subjects walk on a
      split-belt treadmill with symmetric (2 km/h) and asymmetric (2 km/h vs 4 km/h and
      2 km/h vs 6 km/h) belt speeds both with and without a dual auditory Stroop task.
      There was no significant change in response reaction times across walking
      conditions or between walking and standing. The proportion of stance phase was
      unchanged by the dual task during symmetric walking. Stance phase proportions,
      however, significantly increased during dual tasking for the limb on the faster
      belt for both asymmetric conditions, while they decreased for the limb on the
      slower belt for the most asymmetric condition. There were also small
      modifications to double support proportions and a main effect of dual tasking to
      double support proportion variability. Observed dual task changes showed
      interference by the cognitive task with asymmetric gait performance, suggesting
      that asymmetric stepping, such as seen in limping gaits, requires more attention
      than symmetric walking. Such attention may, in part, be due to the dynamic
      balance required in asymmetric limb loading and unloading.

PMID- 19595595
TI  - Comment on "Hypericin uptake: a prognostic marker for survival in high-grade
      glioma".

PMID- 19595593
TI  - Effects of Down syndrome on three-dimensional motion during walking at different
      speeds.
AB  - The inherent joint laxity and muscle hypotonia of adults with Down syndrome (DS)
      may result in reduced gait stability and increased energetic cost. These factors
      vary as a function of walking speed and may be reflected in gait patterns. The
      present study therefore examined whether the three-dimensional motion of the body
      center of mass (COM) and stepping characteristics differ between adults with and
      without DS as a function of speed. Fifteen adults with DS and 15 adults without
      DS underwent a series of treadmill walking trials. Walking speeds were determined
      as Froude numbers, based on leg length. Participants walked at Froude numbers of
      0.1, 0.2, 0.3, 0.4, 0.5, 0.6, and, for adults without DS, 0.7. Whole-body
      kinematic data were collected for 30-35 steps at each speed. Across speeds,
      adults with DS showed greater and more variable mediolateral COM motion than
      adults without DS. COM anteroposterior velocity and vertical motion did not
      differ in range between groups, but were more variable in adults with DS. Adults
      with DS also showed smaller-duration steps and varied their step widths and step
      lengths more than adults without DS. The results suggest a gait pattern with
      lesser stability and greater energetic cost among adults with DS.

PMID- 19595596
TI  - Synthesis, cannabinoid receptor affinity, molecular modeling studies and in vivo
      pharmacological evaluation of new substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H
      pyrazole-3-carboxamides. 2. Effect of the 3-carboxamide substituent on the
      affinity and selectivity profile.
AB  - New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were
      synthesized by replacing the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3
      carboxamide nitrogen of the previously reported CB(1) receptor
      antagonists/inverse agonists 4 and 5. Several ligands showed potent affinity for
      the hCB(1) receptor, with K(i) concentrations comparable to the reference
      compounds 1, 4 and 5, and exhibited CB(1) selectivity comparable to 1 and 2.
      Docking experiments and molecular dynamics (MD) simulations explained the potent
      hCB(1) binding affinity of compounds 31 and 37. According to our previous
      studies, 31 and 37 formed a H-bond with K3.28(192), which accounted for the high
      affinity for the receptor inactive state and the inverse agonist activity. The
      finding of inhibition of food intake following their acute administration to
      rats, supported the concept that the CB(1) selective compounds 4 and 52 act as
      antagonists/inverse agonists.

PMID- 19595597
TI  - Antimicrobial natural products as beta-ketoacyl-acyl carrier protein synthase III
      inhibitors.
AB  - Beta-ketoacyl-acyl carrier protein synthase III (KAS III) initiates bacterial
      fatty acid biosynthesis, making it one of the most promising condensing enzymes.
      In a previous study, we developed three pharmacophore maps from receptor-oriented
      pharmacophore-based in silico screening and proposed a potent antimicrobial
      inhibitor for KAS III. Using these pharmacophore maps, we examined a natural
      product database and chose 4 natural compounds as possible KAS III inhibitors.
      Here, we propose that YKAF01 (3,6-dihydroxyflavone) and YKAF04, 3-(4
      hydroxyphenyl)-1-(2,4,6-tri-hydroxyphenyl)propan-1-one (or 4,2',4',6'-tetra
      hydroxychalcone, phloretin) are potent antimicrobial inhibitors of KAS III with
      high binding affinity. In particular, these compounds display an excellent
      antimicrobial effect against Staphylococcus aureus and MRSA in the range of 16-32
      microM.

PMID- 19595598
TI  - 7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: synthesis and in
      vitro biological evaluation as potential antitumor agents.
AB  - Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and
      apoptotic activities in several cancer cell lines. Moreover, several reports have
      highlighted the interest of increasing the lipophilicity to improve the antitumor
      efficacy. These studies have led us to synthesize new CP derivatives of various
      lipophilicities and to evaluate their activity in five human cancer cell lines.
      With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl)
      derivatives of CP were prepared that displayed IC(50) values ranging from microM
      to mM concentrations and are non-toxic in vivo in healthy mice as shown by their
      maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed
      higher in vitro antitumor activity than parent CP however this was not dependent
      on the lipophilicity of the substituent. Among all synthesized derivatives, the
      most potent were 2 and 6h whose IC(50) values were 10 microM in three (derivative
      2) or four (derivative 6h) cancer cell lines.

PMID- 19595599
TI  - Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3
      morpholino arecoline derivatives in Alzheimer's presenile dementia models.
AB  - Earlier we have reported the effect of arecoline thiazolidinone and morpholino
      arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's presenile
      dementia models. To elucidate further our Structure-Activity Relationship (SAR)
      studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of
      novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3
      yl)morpholine molecule have been designed and synthesized as a new class of M1
      receptor agonists with a low toxicity effect profile that enhances memory
      function in animal models of Alzheimer's presenile dementia and also modulates
      the APP secretion from rat brain cerebrocortical slices by activating M1 receptor
      in vitro. Results suggest that compound 9b having methyl group at the para
      position of the aryl group attached to the carboxamide of morpholino arecoline
      could emerge as a potent molecule having antidementia activity.

PMID- 19595600
TI  - NO-glibenclamide derivatives: prototypes of a new class of nitric oxide-releasing
      anti-diabetic drugs.
AB  - Endothelial dysfunction and consequent reduction of biosynthesis of endogenous
      nitric oxide (NO) play an important pathogenetic role in the cardiovascular
      complications associated with type II diabetes. In this work, the hybrid drugs 3a
      and 3b, nitrooxymethylbenzoate-derivatives of 1 (which is a hydroxylated active
      metabolite of glibenclamide 2), are reported. The pharmacodynamic
      characterization of 3b showed that its hypoglycaemic activity is enriched with
      additional NO-donor effects, conferring vasorelaxing and anti-platelet properties
      of potentially great usefulness for diabetes-related cardiovascular disorders.

PMID- 19595601
TI  - Effects of structural analogues of the substrate and allosteric regulator of the
      human mitochondrial NAD(P)+-dependent malic enzyme.
AB  - Fumarate, a four-carbon trans dicarboxylic acid, is the allosteric activator of
      the human mitochondrial NAD(P)(+)-dependent malic enzyme (m-NAD(P)-ME). In this
      paper, we discuss the effects of the structural analogues of fumarate on human m
      NAD(P)-ME. Succinate, a dicarboxylic acid with a carbon-carbon single bond, can
      also activate the enzyme, but the activating effect of succinate is less than
      that of fumarate. Succinamide, a diamide of succinate, cannot activate the enzyme
      and is a poor active-site inhibitor. The cis isomer of fumarate, maleic acid,
      significantly inhibits the ME activity, suggesting that the trans configuration
      of fumarate is crucial for operating the allosteric regulation of the enzyme.
      Other dicarboxylic acids, including glutaconic acid, malonic acid and alpha
      ketoglutarate, cannot activate the enzyme and inversely inhibit enzyme activity.
      Our data suggest that these structural analogues are mainly active-site
      inhibitors, although they may enter the allosteric site to inhibit the enzyme.
      Furthermore, these data also suggest that the dicarboxylic acid must be in a
      trans conformation for allosteric activation of the enzyme.

PMID- 19595602
TI  - Predictive models, based on classification algorithms, for compounds potentially
      active as mitochondrial ATP-sensitive potassium channel openers.
AB  - Heart mitochondrial ATP-sensitive potassium channel (mito-K(ATP) channels) are
      deeply implicated in the self-defense mechanism of ischemic preconditioning.
      Therefore, exogenous molecules activating these channels are considered as a
      promising pharmacological tool to reduce the myocardial injury deriving from
      ischemia/reperfusion events. In our laboratory, a series of 4-spiro-substituted
      benzopyran derivatives were earlier synthesized and some of them exhibited anti
      ischemic properties. In this study, the above compounds are exploited in order to
      develop QSAR models, based on classification approaches, capable of
      discriminating between the ones acting as cardioprotective agents and those that
      are unable to elicit such a property. Molecules belonging to the whole dataset
      were subjected to CODESSA and E-Dragon calculations in order to compute a large
      number of molecular descriptors enabling the construction of classification
      models. Based on the two program packages used, two different experiments were
      carried out, with the aim of identify batteries of models to be exploited for
      designing new cardioprotective agents from libraries of new chemical entities.
      Both model batteries satisfy the rigorous criteria adopted for the validation,
      either when tested on the training and test set, according to the most
      straightforward protocol, and when tested on an additional prediction set. They
      were proven to ensure successful applications in the field of cardioprotective
      agent design.

PMID- 19595603
TI  - Karyology of parthenogenetic weevils (Coleoptera, Curculionidae): do meiotic
      prophase stages occur?
AB  - We investigated the cytological mechanism of parthenogenesis by analyzing the
      chromosomes in five weevil species. All examined species are polyploids, four of
      which: Otiorhynchus ovatus, Simo variegates, Cathormiocerus aristatus, and
      Tropiphorus elevatus possess three haploid sets of chromosomes (3n=33), whereas
      the fifth, Trachyphloeus parallelus, is tetraploid with 44 chromosomes (4n=44).
      The plates contained 27-31 chromosomes in triploid species and 38, 39, 41 and
      even 44 in tetraploid T. parallelus. In all species single clusters of metaphase
      plates with a haploid number of n=11 were visible. Some oogonial cells showed
      nuclei configurations resembling the stages of diplotene and diakinesis. The
      spiralized chromosomes in these nuclei may have been connected by chiasmata
      resulting in rods figures and ring-shaped bivalents. Occurrence of the remnants
      of meiosis could suggest some degree of recombination in parthenogenetic lineages
      of weevils.

PMID- 19595604
TI  - Monitoring of mechanical properties of serially passaged bovine articular
      chondrocytes by atomic force microscopy.
AB  - Atomic force microscopy (AFM) is a powerful tool in imaging cells and tissues and
      probing their mechanical properties. Articular chondrocytes, the cells
      responsible for the production and maintenance of cartilaginous extracellular
      matrix in the knee joint, change their morphology and dedifferentiate during in
      vitro expansion culture. It was unclear if the mechanical properties of
      chondrocytes change accompanying phenotype variation. The elasticity of in vitro
      serially cultured bovine articular chondrocytes was investigated using AFM. The
      chondrocytes changed their morphology from round to spindle-like. The freeze
      dried P0 chondrocytes showed significantly higher modulus than did the serially
      passaged (P1-P4) chondrocytes. The change of chondrocyte morphology was
      accompanied with a decrease of elastic modulus.

PMID- 19595605
TI  - TachoSil surgical patch versus conventional haemostatic fleece material for
      control of bleeding in cardiovascular surgery: a randomised controlled trial.
AB  - OBJECTIVE: Prolonged bleeding during cardiovascular surgery presents a risk for
      the patient and increases the time and cost of surgery. TachoSil is a ready-to
      use haemostatic agent that consists of an equine collagen patch coated with human
      fibrinogen and thrombin. This trial evaluated the efficacy and safety (< or =30
      days post-surgery) of TachoSil surgical patch compared with standard haemostatic
      fleece for the control of bleeding in patients undergoing cardiovascular surgery.
      METHODS: Patients scheduled for elective surgery on the heart, ascending aorta or
      aortic arch requiring cardiopulmonary bypass were eligible for this open-label
      multicentre trial. After primary haemostatic measures, patients were randomised
      to TachoSil or conventional haemostatic fleece if an area of persisting
      haemorrhage was identified (target area). After the application of trial
      treatment, haemostasis was evaluated at 3 min (primary endpoint). If haemostasis
      was not achieved, trial treatment was re-applied and haemostasis assessed at 6
      min (secondary endpoint). RESULTS: A total of 120 patients were randomised and
      119 received trial treatment (TachoSil, n=59; standard treatment, n=60). Twenty
      six percent of patients were female and the mean age was 67 years (range: 23-86
      years). Baseline characteristics were similar in both the groups. Bleeding
      occurred mainly from the aorta (56%), right ventricle (16%) or right atrium
      (13%), more often from a vessel (68%) than tissue (32%), and was assessed to be
      arterial in 74% of cases. TachoSil was significantly superior to standard
      haemostatic fleece in controlling bleeding after insufficient primary
      haemostasis, with 75% (95% confidence interval (CI): 0.64-0.86) of the TachoSil
      group achieving haemostasis at 3 min compared with only 33% (95% CI: 0.21-0.45)
      of the standard treatment group (p<0.0001). This difference persisted at 6 min,
      with 95% of patients achieving haemostasis in the TachoSil group compared with
      72% in the standard treatment group (p=0.0006). Three (5%) TachoSil patients
      compared with 17 (28%) standard treatment patients failed to achieve haemostasis
      at 6 min and received rescue treatment. TachoSil was well tolerated with adverse
      events generally similar in the two treatment groups. CONCLUSIONS: TachoSil was
      significantly superior to standard haemostatic fleece material in obtaining
      effective and fast intra-operative haemostasis in cardiovascular surgical
      procedures. TachoSil was safe and well tolerated.

PMID- 19595606
TI  - Treatment of complicated pulmonary aspergillomas with cavernostomy and muscle
      flap: interest of concomitant limited thoracoplasty.
AB  - OBJECTIVE: Lung resection for complex aspergilloma (CA) carries high morbidity
      and mortality and remains controversial in high-risk patients. Cavernostomy
      followed by muscle-flap plombage has been recommended for patients considered
      unfit for resection, but subsequent muscle-flap atrophy may be a main cause of
      failure. We reviewed the place of a limited thoracoplasty in association with
      that procedure. METHODS: Five patients complaining of haemoptysis related to CA
      were denied lung resection because of bilateral lung destruction (n=1), and
      required completion pneumonectomy (previous lobectomy for cancer followed by
      adjuvant radiation therapy, n=4). We analysed the data concerning the alternative
      surgical procedures performed and their immediate and late results. RESULTS: The
      surgery consisted in cavernostomy, removal of the fungus ball, cavity
      obliteration with the most directly available muscle flaps (rhomboid muscle n=2,
      trapezius and rhomboid n=2, serratus major and subscapular n=1). A limited
      thoracoplasty ranging from 2 to 5 portions of rib (mean resected rib portions
      n=3.4) was performed in addition to this procedure. The postoperative course was
      uneventful. All patients are still alive (mean follow-up 3 years; range: 1-6
      years) and faring well without thoracoplasty-related aftereffect, complication
      related to muscle-flap disuse atrophy nor recurrence of the disease. CONCLUSION:
      Cavernostomy followed by muscle transposition has been reported to provide
      encouraging results. Combining a limited thoracoplasty during the same operation
      is a simple, safe and well-tolerated procedure regularly achieving good results,
      and thus deserving consideration.

PMID- 19595607
TI  - Editorial comment.

PMID- 19595608
TI  - Errors in administration of parenteral medications are a serious safety problem
      in intensive care units.
AB  - This research review aimed to critically appraise the study by Valentin et al. on
      administration errors for parenteral medications in intensive care units.

PMID- 19595609
TI  - What is the true nature of the osteoblastic hematopoietic stem cell niche?
AB  - The recently revitalized interest in the regulation of hematopoietic stem cells
      (HSCs) by the bone marrow microenvironment has resulted in the identification of
      some important cell types that potentially form the HSC niche. The term
      'osteoblast' has commonly been used to describe the endosteal elements of the HSC
      niche, but these cells are part of a larger family that functions in bone at
      different stages of differentiation. Given that there is much controversy as to
      what cell types have important roles in the HSC niche, this review offers an
      overview of the diverse osteoblastic cell types and discusses the current
      evidence regarding what roles they have in the HSC niche.

PMID- 19595610
TI  - PXR and CAR in energy metabolism.
AB  - The nuclear receptors pregnane X receptor (PXR, or NR1I2) and constitutive
      androstane receptor (CAR, or NR1I3) were originally identified as xenosensors
      that regulate the expression of Phase I and Phase II drug-metabolizing enzymes
      and transporters. Recent results suggest that PXR and CAR also have important
      endobiotic roles in energy metabolism by affecting the metabolism of fatty acids,
      lipids and glucose. PXR and CAR exert their effects on energy metabolism through
      direct gene regulation or through crosstalk with other transcriptional
      regulators. This review focuses on the roles of CAR and PXR in energy metabolism
      and offers a perspective on whether PXR and CAR represent novel therapeutic
      targets for the management of metabolic syndrome.

PMID- 19595611
TI  - Mining incretin hormone pathways for novel therapies.
AB  - The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and
      glucagon-like peptide-1 (GLP-1), are produced predominantly by enteroendocrine
      cells and have multiple blood glucose-lowering effects. Recent years have seen a
      surge of interest in understanding the basic physiology and pathophysiology of
      incretins and in applying this knowledge to the treatment of diabetes and
      obesity. Considerable gains have been made in elucidating the mechanisms
      controlling incretin secretion, and there is growing evidence to suggest that
      incretins might be involved in the rapid reversal of diabetes observed in gastric
      bypass patients. Here, we review these recent advances and outline the multiple
      strategies being pursued to exploit the potential therapeutic benefits of GIP and
      GLP-1.

PMID- 19595613
TI  - Influence of back muscle fatigue on lumbar reflex adaptation during sudden
      external force perturbations.
AB  - There is still conflicting evidence about the influence of fatigue on trunk
      reflex activity. The aim of this study was to measure response latency and
      amplitude changes of lumbar and abdominal muscles after heavy external force
      perturbation applied to the trunk in the sagittal plane before and after back
      muscle fatigue, in expected and unexpected conditions. Ten healthy subjects in a
      semi-seated position, torso upright in a specific apparatus performed an
      intermittent back muscle fatigue protocol. EMG reflex activity of erector spinae
      (ES) and external oblique muscles were recorded in unexpected and in expected
      (self pre-activation) conditions. After fatigue, the normalized reflex amplitude
      of ES increased in expected and unexpected conditions (P<0.05) while ES response
      latency was slightly decreased. Reflexes latencies for ES were systematically
      shorter (P<0.05) of 25% in expected compared to unexpected conditions. These
      findings suggest that a large external force perturbation would elicit higher
      paraspinal magnitude responses and possible earlier activation in order to
      compensate the loss of muscular force after fatigue. Because of the seated
      position the postural adjustments were probably not triggered and thus explain
      the lack of abdominal activation. The self-anticipated pre-activation in order to
      counteract perturbations was not affected by fatigue illustrating the natural
      muscular activation to maintain trunk stability.

PMID- 19595612
TI  - CD40 and autoimmunity: the dark side of a great activator.
AB  - CD40 is a tumor necrosis factor receptor superfamily member expressed by immune
      and non-immune cells. CD40:CD154 interactions mediate T-dependent B cell
      responses and efficient T cell priming. Thus, CD40 is a likely candidate to play
      roles in autoimmune diseases in which activated T and B cells cause pathology.
      Diseases in which CD40 plays a pathogenic role include autoimmune thyroiditis,
      type 1 diabetes, inflammatory bowel disease, psoriasis, multiple sclerosis,
      rheumatoid arthritis, and systemic lupus erythematosus. This review discusses the
      role of CD40:CD154 interaction in human and mouse autoimmunity, human
      polymorphisms associated with disease incidence, and disrupting CD40:CD154
      interactions as an autoimmune therapy.

PMID- 19595614
TI  - Contemporary outcome and management of patients who had an aborted cystectomy due
      to unresectable bladder cancer.
AB  - OBJECTIVES: Aborted cystectomy due to unresectable disease is not uncommon in
      patients with bladder cancer. Our aim was to review the outcome of these patients
      and evaluate various prognostic variables. MATERIALS AND METHODS: Thirty-one
      bladder cancer patients who underwent aborted radical cystectomy due to
      unresectable disease from 1993 to 2007, and form the basis of this report.
      Survival was estimated by the Kaplan and Meier method, with Cox proportional
      hazards regression model used to evaluate associations between survival and
      variables studied. RESULTS: Mean age of patients was 66 years with median follow
      up of patients alive 10 months. The 2- and 5-year overall survival (OS) was 41%
      and 0%, respectively. Twenty patients had a pelvic lymph node dissection (PLND)
      and 11 patients did not. Twenty-three patients received postoperative therapy, of
      whom 8 received chemotherapy with the intent of surgical consolidation (only 2
      were rendered resectable thereafter), and 15 received combined chemoradiation. OS
      was not significantly associated with hydronephrosis, concomitant CIS,
      performance status, history of superficial tumors, postoperative therapy, and
      salvage cystectomy. Patients with pN2-3 had similar overall survival compared
      with those with pT4b (13 vs. 17 months, P=0.59). However, patients who underwent
      PLND trended towards improved OS compared with those who did not (24 vs. 10
      months, P=0.09). CONCLUSIONS: Outcome of patients with unresectable disease is
      dismal. Patients who had an aborted cystectomy due to unresectable disease may
      benefit from PLND. Further refinements of clinical staging to better identify
      these patients preoperatively and offer them upfront chemotherapy are needed.

PMID- 19595617
TI  - Enhancing MQMAS of low-gamma nuclei by using a high B(1) field balanced probe
      circuit.
AB  - A balanced probe circuit is used to generate high B(1) magnetic field for
      sensitivity enhancement of multiple-quantum magic-angle spinning (MQMAS)
      experiment applied to low-gamma quadrupolar nuclei. Electrical balancing of the
      sample coil can cut the peak voltage by a half, therefore improving the power
      handling when generating a two-fold higher B(1) field. Experimental results,
      illustrated here with (25)Mg data for two layered double hydroxides, show that
      the MQMAS efficiency increases more than linearly with the B(1) field strength.
      The multiplicative enhancements from high B(0) and B(1) fields and an optimized
      MQMAS pulse sequence provide the critically needed sensitivity for acquiring
      MQMAS spectra of low-gamma quadrupolar nuclei such as (25)Mg at natural
      abundance.

PMID- 19595615
TI  - Therapeutic options and patterns of prescription in chronic venous disorders:
      results of a 3-year survey in Italy.
AB  - OBJECTIVES: To assess self-management of chronic venous disorders (CVDs) in a
      selected Italian population and the pattern of prescription by selected Italian
      phlebologists. DESIGN: Cross-sectional study carried out between 2003 and 2005.
      MATERIALS: Non-random, transverse sample of men and women recruited by
      advertising. METHODS: Assessment of therapeutic habits of respondents, treatment
      advice given by phlebologists related to socio-demographic variables and severity
      of the disease. Multivariate odds ratios for sex, age, class, region, family
      history and severity of the disease. RESULTS: Women undergo CVD therapy more than
      men (odds ratio (OR): 2.37 for medical treatment; 1.29 for surgical treatment and
      5.72 for sclerotherapy). Young people prefer drug treatment to compression
      stockings. Drug therapy for CVD is 1.5 times more likely in southern Italian
      respondents, as is compression stockings (OR: 1.91). Surgical therapy is more
      frequent in Northern Italy (OR for Central Italy: 0.79; Southern Italy and
      Islands: 0.76). Family history of CVD leads people to early treatment of
      symptoms. CONCLUSIONS: This study provides insight into self-medication of CVD in
      Italy and the prescribing patterns of Italian phlebologists in the treatment of
      CVD. It shows that the population interviewed is able to practise responsible
      self-medication of their CVD problems.

PMID- 19595618
TI  - Simple RF design for human functional and morphological cardiac imaging at
      7tesla.
AB  - Morphological and functional cardiac MRI can potentially benefit greatly from the
      recent advent of commercial high-field (7tesla and above) MRI systems. However,
      conventional hardware configurations at lower field using a body-coil for
      homogeneous transmission are not available at these field strengths.
      Sophisticated multiple-transmit-channel systems have been shown to be able to
      image the human heart at 7tesla but such systems are currently not widely
      available. In this paper, we empirically optimize the design of a simple
      quadrature coil for cardiac imaging at 7tesla. The size, geometry, and position
      have been chosen to produce a B(1) field with no tissue-induced signal voids
      within the heart. Standard navigator echoes for gating were adapted for operation
      at the heart/lung interface, directly along the head-foot direction. Using this
      setup, conventional and high-resolution cine functional imaging have been
      successfully performed, as has morphological imaging of the right coronary
      artery.

PMID- 19595620
TI  - Review on aspects of artificial tactile feedback in laparoscopic surgery.
AB  - Since direct manual tissue palpation is not possible in laparoscopic surgery,
      feedback information on tactile tissue properties is considerably diminished.
      Restoring part of the surgeon's sense of touch through devices capable of
      providing artificial tactile feedback (ATF) is an active field of applied
      research and development. Despite more than two decades of research, technical
      development of such devices is still basic, and pre-clinical as well as clinical
      experience is limited. This article provides an overview of the technological
      aspects of ATF in laparoscopic surgery, gives background information on
      principles of human perception of related feedback information, and reviews
      current research attempts in the field of ATF systems in laparoscopic surgery,
      broken down into three main system components: tactile sensor, display, and data
      processing. Tactile sensors have been developed to measure tissue compliance,
      reveal hidden structures or foreign bodies in tissue through measurement of
      pressure distribution, and to identify and locate arteries by detecting their
      pulsation. Furthermore, different solutions for presenting tactile data to the
      surgeon have been developed. Visual and auditory displays are easy to implement
      into the operating room equipment, while tactile displays still suffer from
      difficulties concerning their performance and requirements for clinical
      usability. The role of the data processing system as the linking component in an
      artificial tactile feedback system has been identified as crucial for
      effectiveness of the system and easy reception of tactile data by the surgeon.
      The investigations on theoretical and technological foundations of ATF have led
      to an extensive database in recent years. An application-driven development
      approach will likely be a driving factor in the future evolution of this field.

PMID- 19595619
TI  - Substrate reduction therapy in juvenile GM2 gangliosidosis.
AB  - Substrate reduction therapy (SRT) is considered to be a potential therapeutic
      option for juvenile GM2 gangliosidosis (jGM2g). We evaluated the efficacy of SRT
      in jGM2g, assessing neurological, neuropsychological and brain magnetic resonance
      imaging (MRI) outcomes over a 24-month period of treatment. In an open-label and
      single-center study, five jGM2g patients (mean age 14.6+/-4.5 years) received
      oral miglustat at doses of 100-200mg t.i.d. adjusted to body surface area.
      Patients underwent general and neurological examinations, neuropsychological,
      electrophysiological, and brain MRI studies. All patients showed neurological
      deterioration over the period of the study, with particularly notable worsening
      of gait, speech and coordination. One patient experienced acute psychosis, and
      another showed worsening of pre-existing epilepsy. Some neuropsychological tests
      showed no evidence of deterioration in the three patients with high enough
      cognitive functioning for reliable assessment. Profound cognitive impairment in
      two children precluded neuropsychological evaluation. In four patients,
      evaluation of brain MRI showed no changes in white matter signal abnormalities
      and cerebellar atrophy noted at baseline, while one patient showed progression of
      cerebellar and supratentorial brain atrophy. Transmission electron microscopy
      analysis of peripheral mononuclear cells showed reduction of intracytoplasmatic
      inclusions with treatment. SRT with miglustat of patients with jGM2g failed to
      ameliorate progressive neurological deterioration, but apparently no worsening of
      some areas of cognitive function tested and brain MRI lesions was noted over 24
      months of treatment. The results must be interpreted with care owing to the small
      sample of patients and the lack of a control-arm.

PMID- 19595621
TI  - Can in vitro systems capture the characteristic differences between the flexion
      extension kinematics of the healthy and TKA knee?
AB  - In vitro systems provide a powerful means to evaluate the efficacy of total knee
      arthroplasty (TKA) in restoring normal knee kinematics. The Oxford knee rig (OKR)
      and the robotic knee testing system (RKTS) represent two systems that have been
      extensively used to study TKA biomechanics. Nonetheless, a frequently asked
      question is whether in vitro simulations can capture the in vivo behavior of the
      knee. Here, we compared the flexion-extension kinematics of intact knees and
      knees after TKA tested on the OKR and RKTS, to results of representative in vivo
      studies. The goal was to determine if the in vitro systems could capture the key
      kinematic features of knees in healthy subjects and TKA patients. Results showed
      that the RKTS and the OKR can replicate the femoral rollback and 'screw home'
      tibial rotation between 0 degrees and 30 degrees flexion seen in healthy
      subjects, and the reduced femoral rollback and absence of 'screw home' motion in
      TKA patients. The RKTS also replicated the overall internally rotated position of
      the tibia beyond 30 degrees flexion. However, ability of the OKR to replicate the
      internally rotated position of the knee beyond 30 degrees flexion was
      inconsistent. These data could aid in validation of new in vitro systems and
      physiologic interpretations of in vitro results.

PMID- 19595622
TI  - Experimental modelling of aortic aneurysms: novel applications of silicone
      rubbers.
AB  - A range of silicone rubbers were created based on existing commercially available
      materials. These silicones were designed to be visually different from one
      another and have distinct material properties, in particular, ultimate tensile
      strengths and tear strengths. In total, eleven silicone rubbers were
      manufactured, with the materials designed to have a range of increasing tensile
      strengths from approximately 2 to 4 MPa, and increasing tear strengths from
      approximately 0.45 to 0.7 N/mm. The variations in silicones were detected using a
      standard colour analysis technique. Calibration curves were then created relating
      colour intensity to individual material properties. All eleven materials were
      characterised and a 1st order Ogden strain energy function applied. Material
      coefficients were determined and examined for effectiveness. Six idealised
      abdominal aortic aneurysm models were also created using the two base materials
      of the study, with a further model created using a new mixing technique to create
      a rubber model with randomly assigned material properties. These models were then
      examined using videoextensometry and compared to numerical results. Colour
      analysis revealed a statistically significant linear relationship (p<0.0009) with
      both tensile strength and tear strength, allowing material strength to be
      determined using a non-destructive experimental technique. The effectiveness of
      this technique was assessed by comparing predicted material properties to
      experimentally measured methods, with good agreement in the results.
      Videoextensometry and numerical modelling revealed minor percentage differences,
      with all results achieving significance (p<0.0009). This study has successfully
      designed and developed a range of silicone rubbers that have unique colour
      intensities and material strengths. Strengths can be readily determined using a
      non-destructive analysis technique with proven effectiveness. These silicones may
      further aid towards an improved understanding of the biomechanical behaviour of
      aneurysms using experimental techniques.

PMID- 19595623
TI  - Huntington's disease-like and ataxia syndromes: identification of a family with a
      de novo SCA17/TBP mutation.
AB  - The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are
      clinically and genetically heterogeneous neurodegenerative disorders. Twenty
      eight genetic subtypes have been identified, of which 7 are caused by expansion
      of a CAG trinucleotide repeat that encodes a polyglutamine tract in the
      respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA
      box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17
      overlaps that of Huntington's disease (HD), hence the use of the term
      Huntington's disease-like. We screened 89 patients with a Huntington's disease
      like phenotype without the HD-gene mutation and 178 patients with genetically
      unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman
      presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion
      was identified. Her normal allele included 38 repeats. The patient's mother and
      father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis
      of the repeat structures revealed that the expansion had occurred upon expansion
      of the longer paternal allele. We conclude that, however rare, SCA17 must be
      considered as a cause of Huntington's disease-like phenotypes and ataxia
      syndromes, also in isolated cases.

PMID- 19595624
TI  - The Roundtable on Sustainable Biofuels: plant scientist input needed.
AB  - The Energy Center at the Ecole Polytechnique Federale de Lausanne (Swiss federal
      institute of technology) is coordinating a multi-stakeholder effort, the
      Roundtable on Sustainable Biofuels (http://energycenter.epfl.ch/biofuels), to
      develop global standards for sustainable biofuels production and processing.
      Given that many of the aspects related to biofuel production request a high
      scientific level of understanding, it is crucial that scientists take part in the
      discussion.

PMID- 19595625
TI  - Corticocentric myopia: old bias in new cognitive sciences.
AB  - Traditionally, the cerebral cortex is seen to have the most important role in
      'higher' functions of the brain, such as cognition and behavioral regulation,
      whereas subcortical structures are considered to have subservient or no roles in
      these functions. This article highlights the conceptual bias at the root of this
      corticocentric view of the human brain, and emphasizes its negative implications
      in current practices in the cognitive neurosciences. The aim of this article is
      to suggest that the 'corticocentric' view of the human brain is also a myopic
      view because it does not let us see that the 'higher' functions of the brain
      might in fact depend on the integrity of its 'lower' structures.

PMID- 19595626
TI  - Stochastic gene expression as a molecular switch for viral latency.
AB  - Stochastic 'noise' arises from random thermal fluctuations in the concentration
      of protein, RNA, or other molecules within the cell and is an unavoidable aspect
      of life at the single-cell level. Evidence is accumulating that this biochemical
      noise crucially influences cellular auto-regulatory circuits and can 'flip'
      genetic switches to drive probabilistic fate decisions in bacteria, viruses,
      cancer, and stem cells. Here, we review how stochastic gene expression in key
      auto-regulatory proteins can control fate determination between latency and
      productive replication in both phage-lambda and HIV-1. We highlight important new
      studies that synthetically manipulate auto-regulatory circuitry and noise, to
      bias HIV-1's ability to enter proviral latency. We argue that an appreciation of
      noise in gene expression may shed light on the mystery of animal virus latency
      and that strategies to manipulate noise may have impact on anti-viral
      therapeutics.

PMID- 19595627
TI  - AASM PSG manual: the R&K update?

PMID- 19595628
TI  - Paradoxical insomnia: the role of CAP and arousals in sleep misperception.
AB  - OBJECTIVE: The relationship between CAP parameters and subjective time perception
      during sleep in primary insomnia was investigated. PATIENTS AND METHODS: Data
      collected from all-night PSG recordings of 20 patients with a diagnosis of
      paradoxical insomnia (misperceptors) were compared with those of 20 normal gender
      and age-matched subjects (controls). Besides sleep staging, scoring measures
      included CAP parameters and EEG arousals. RESULTS: Patients and controls
      presented non-significant differences in the amounts of objective sleep time (464
      min vs. 447 min) and objective sleep latency (9 min vs. 8 min). Compared to
      controls, misperceptors reported a significantly shorter time of perceived sleep
      (285 min vs. 461 min) and a significantly longer duration of perceived sleep
      latency (51 min vs. 22 min). In spite of the 11 objective awakenings,
      misperceptors reported only 4 subjective awakenings, while controls described 2
      of the 5 objective awakenings. Arousal index (31.7/h vs. 18.6/h) and total CAP
      rate (58.1% vs. 35.5%) were significantly higher in misperceptors. In the sleep
      period between objective and subjective sleep onset, CAP rate was 64.4% in
      misperceptors and 45.1% in controls (p<0.002). Insomniacs showed significantly
      higher amounts of CAP rate in stage 1 (62.7% vs. 37.5%) and in stage 2 (53.3% vs.
      33.1%), but not in slow wave sleep. CAP phase A2 subtypes were significantly
      increased in misperceptors (31% vs. 24%). CONCLUSIONS: The study points out the
      topical role of enhanced activation and arousal instability not only in the first
      part of the night (mismatch between objective and subjective sleep onset) but
      also in the misperception of consecutive objective awakenings which are
      subjectively grouped together as a single prolonged event.

PMID- 19595629
TI  - Changes of cortical excitability after dopaminergic treatment in restless legs
      syndrome.
AB  - OBJECTIVE: Dopaminergic pathways are most likely involved in the pathophysiology
      of restless legs syndrome (RLS). In previous investigations, an alteration of
      cortical excitability was suggested to be related to a dopaminergic dysfunction
      in RLS. The purpose of our study was to compare practice-dependent plasticity in
      RLS patients before and after a month of dopaminergic treatment. METHODS: Single
      pulse transcranial magnetic stimulation (TMS) was used to define motor evoked
      potential (MEP) amplitude, motor threshold, and silent period (SP) as well.
      Subjects performed three exercise blocks (bimanual motor task). MEP amplitude,
      registered immediately after each exercise block and after a rest period, was
      compared to baseline. The time course of intra-cortical inhibition was tested
      using paired-pulse TMS at short inter-stimulus intervals. For the single-pulse
      TMS procedures, we enrolled 12 patients affected by primary RLS and 12 normal
      subjects. For the paired-pulse TMS procedures, only six patients underwent the
      examination. RLS patients underwent the examination in both pre- and post
      dopaminergic treatment conditions. RESULTS: In RLS patients MEP amplitude
      increased after the rest period only in the post-treatment condition, showing a
      delayed facilitation. After exercise, MEP amplitude increased, but not enough to
      be significant, showing a positive trend but not a clear-cut post-exercise
      facilitation. In the pre-treatment condition instead, MEP amplitude did not
      change either after rest period or after exercise. RLS patients showed a marked
      increase of the central motor inhibition, assessed by using paired-pulse TMS at
      short inter-stimulus intervals after pramipexole treatment. On the contrary, the
      duration of the SP did not change compared to the pre-treatment condition.
      CONCLUSIONS: In RLS patients after dopaminergic treatment, the main finding was
      the changing of MEP amplitude after rest following a motor task. Since
      dopaminergic treatment can reverse delayed facilitation in RLS, we hypothesized
      that cortical plasticity related to dopaminergic systems may play a crucial role
      in RLS pathophysiology.

PMID- 19595630
TI  - Evidence for the validity of the Children's Attraction to Physical Activity
      questionnaire (CAPA) with young children.
AB  - Attraction to physical activity is important to an individual's intrinsic
      motivation to engage in play, games and sports. While there are instruments
      designed to measure attraction to physical activity in middle childhood years,
      the lack of authentic measures in young children has impeded research in this
      area. In this study we sought to address the validity of a scale to tap young
      children's attraction to physical activity. Evidence for validity was based on
      internal consistency, content analysis, and factor structure. Australian school
      children (180 boys and 154 girls) from school year two, aged 6-8 years, were
      individually administered a modified version of the Children's Attraction to
      Physical Activity Scale (CAPA) [Brustad RJ. Who will go out to play? Parental and
      psychological influences on children's attraction to physical activity. Pediatr
      Exerc Sci 1993;5:210-23; Brustad RJ. Attraction to physical activity in urban
      school children: parental socialization and gender influences. Res Q Exerc Sport
      1996;67:316-23]. The results indicated that internal consistency was acceptable
      for most of the subscales when negative statements were excluded from the
      analyses. Factor analysis revealed that the liking of games and sports, liking of
      physical exertion and exercise, and the importance of exercise subscales were
      more robust. Second order factor analysis indicated that the overall construct of
      attraction to physical activity was viable in this age group. With some
      modifications, the scale appears to provide a valid approach to the measurement
      of attraction to physical activity in young children.

PMID- 19595632
TI  - Whose side are you on? The diagnostic conundrum of solitary crossed renal
      ectopia.
AB  - A 56-year-old man presents with haematuria and through extensive investigation is
      found to have solitary crossed renal ectopia. This congenital abnormality occurs
      as a result of a combination of unilateral renal agenesis and renal ectopia. With
      only 34 cases reported in the worldwide literature, the rarity of solitary
      crossed renal ectopia makes its diagnosis a challenge. We review the
      embryological theories behind this congenital anomaly and highlight some of the
      typical features demonstrated in our case that would lead one to consider a
      diagnosis of solitary crossed renal ectopia. We also describe features which have
      not previously been noted in case reports.

PMID- 19595631
TI  - Analysis of the fusA2 locus encoding EFG2 in Mycobacterium smegmatis.
AB  - The translation elongation factor G (EFG) is encoded by the fusA gene. Several
      bacteria possess a second fusA-like locus, fusA2 which encodes EFG2. A comparison
      of EFG and EFG2 from various bacteria reveals that EFG2 preserves domain
      organization and maintains significant sequence homology with EFG, suggesting
      that EFG2 may function as an elongation factor. However, with the single
      exception of a recent study on Thermus thermophilus EFG2, this class of EFG-like
      factors has not been investigated. Here, we have characterized EFG2 (MSMEG_6535)
      from Mycobacterium smegmatis. Expression of EFG2 was detected in stationary phase
      cultures of M. smegmatis (Msm). Our in vitro studies show that while MsmEFG2
      binds guanine nucleotides, it lacks the ribosome-dependent GTPase activity
      characteristic of EFGs. Furthermore, unlike MsmEFG (MSMEG_1400), MsmEFG2 failed
      to rescue an E. coli strain harboring a temperature-sensitive allele of EFG, for
      its growth at the non-permissive temperature. Subsequent experiments showed that
      the fusA2 gene could be disrupted in M. smegmatis mc(2)155 with Kan(R) marker.
      The M. smegmatis fusA2::kan strain was viable and showed growth kinetics similar
      to that of the parent strain (wild-type for fusA2). However, in the growth
      competition assays, the disruption of fusA2 was found to confer a fitness
      disadvantage to M. smegmatis, raising the possibility that EFG2 is of some
      physiological relevance to mycobacteria.

PMID- 19595633
TI  - In memoriam: Susan S. Spencer, MD.

PMID- 19595634
TI  - Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in
      breast cancer patients previously treated with paclitaxel.
AB  - Neuropathic pain (NP) remains difficult to control for a significant number of
      patients with cancer. Chemotherapy-induced peripheral neuropathy (CIPN) has been
      postulated as an initial stage in the development of NP. To assess whether CIPN
      (defined as National Cancer Institute Common Toxicity Criteria grade 2 or higher)
      was associated with NP, we conducted a survey of breast cancer patients who had
      participated in clinical trials of paclitaxel. Of the 430 potential respondents,
      240 responded to the survey. Results showed that 64% experienced CIPN during
      paclitaxel treatment. Follow-up survey data revealed that 27% of those with CIPN
      were subsequently diagnosed with NP. Logistic regression analyses showed that
      those who had experienced CIPN were 3 times more likely to develop NP (95%
      confidence interval = 1.2-7.2; P < .001), which persisted in the multivariate
      logistic model. In addition, NP patients reported twice as many visits to their
      health care provider (P = .02) and had taken more prescription (50% vs 19%; P =
      .001) and over-the-counter medications (62.5% versus 45%; P = .08) for pain than
      those without NP. The results of this study confirm that CIPN is a predictor of
      NP, suggesting that survivors treated with paclitaxel should be regularly
      monitored for NP beyond treatment. PERSPECTIVE: The survival rates of breast
      cancer patients have steadily improved over recent years; thus, research into
      symptoms that persist after treatment is important. We found CIPN as a predictor
      of NP. Understanding the epidemiology of NP in breast cancer patients has high
      clinical and public health significance.

PMID- 19595635
TI  - Pain coping in Latino populations.
AB  - Although there has been a rapid increase in Latino populations in the United
      States over the last 10 years, health research with Latino cultural groups is
      sorely lacking. In the area of pain-coping research, one consequence of the
      limited research is that very little is known about pain coping among Latinos.
      The purpose of this paper is to review the existing literature on pain coping in
      Latino populations, and to propose new directions for the future study of pain
      coping in Latino populations. This review is divided into 4 sections. In the
      first section, the challenges of defining Latino populations are discussed. In
      the second section, the current literature on pain coping in Latinos is reviewed.
      Third, we discuss the implications of existing findings for pain-coping
      assessment and pain treatment. Finally, we offer ideas for future research on
      pain coping in Latino populations. PERSPECTIVE: In this review article, we
      identify gaps in our current understanding of pain coping in Latino cultural
      groups, and associated implications for pain assessment and treatment. We also
      highlight potential directions for future pain-coping research with Latino
      populations.

PMID- 19595637
TI  - A neuropsychological model of pain: research and clinical implications.
AB  - This focus article argues that it may be useful to consider, and expand research
      into, studying the associations between psychological treatments and cortical
      activity. Matching our current understanding of the content and goals of
      psychological pain treatments with knowledge regarding the primary cortical areas
      involved in the processing and experience of pain provides an initial step
      towards a neuropsychological model of pain. This model can be used to: (1) inform
      research and increase knowledge about the associations between cortical activity,
      pain treatment, and pain experience; (2) facilitate communication about
      psychological treatments with patients to facilitate treatment engagement; and
      (3) help guide the development of more effective treatment plans. In this way,
      the development, testing, and modification of a neuropsychological model of pain
      could result in more patients receiving more effective care. PERSPECTIVE: A model
      that describes the effects of psychological treatments on specific pain-related
      cortical areas and processes could inform researchers who test hypotheses
      concerning the mechanisms of those treatments, and help pain clinicians develop
      more effective treatment plans.

PMID- 19595638
TI  - Diagnosis-specific management of somatoform disorders: moving beyond "vague
      complaints of pain".
AB  - The DSM IV category, somatoform disorders, is composed of disorders that are
      characterized by symptom amplification-most typically, amplification of pain.
      Other than this commonality, there is considerable variability among the
      disorders in terms of etiology, course, comorbidities, and the presence or
      absence of insight. The heterogeneous nature of the somatoform group has led to
      calls to remove or radically alter the category in the next DSM revision. Despite
      these concerns, teaching articles addressing somatoform disorders tend to
      generalize across the category when making patient treatment recommendations. In
      this report, the authors encourage moving beyond catch phrases such as, "the
      somatic patient" and "vague complaints of pain," and toward accurate differential
      diagnosis between somatoform disorders. They argue that accurate diagnosis of
      somatoform disorders is both achievable and necessary to provide optimal care for
      this diverse population of patients. Diagnosis and patient-centered management is
      contrasted with more generalized treatment recommendations. PERSPECTIVE: This
      article highlights the appropriate diagnosis and treatment of somatoform
      disorders for patients with pain. In contrast to the majority of literature on
      the subject, the authors emphasize the importance of differential diagnosis
      between somatoform disorders as well as patient-specific and diagnosis-specific
      treatment. The authors argue that there has been an incorrect tendency to
      overgeneralize across disorders, an error that is magnified by the exceptional
      weakness of the somatoform category.

PMID- 19595636
TI  - Development and preliminary testing of a computerized adaptive assessment of
      chronic pain.
AB  - The aim of this article is to report the development and preliminary testing of a
      prototype computerized adaptive test of chronic pain (CHRONIC PAIN-CAT) conducted
      in 2 stages: (1) evaluation of various item selection and stopping rules through
      real data-simulated administrations of CHRONIC PAIN-CAT; (2) a feasibility study
      of the actual prototype CHRONIC PAIN-CAT assessment system conducted in a pilot
      sample. Item calibrations developed from a US general population sample (N = 782)
      were used to program a pain severity and impact item bank (kappa = 45), and real
      data simulations were conducted to determine a CAT stopping rule. The CHRONIC
      PAIN-CAT was programmed on a tablet PC using QualityMetric's Dynamic Health
      Assessment (DYHNA) software and administered to a clinical sample of pain
      sufferers (n = 100). The CAT was completed in significantly less time than the
      static (full item bank) assessment (P < .001). On average, 5.6 items were
      dynamically administered by CAT to achieve a precise score. Scores estimated from
      the 2 assessments were highly correlated (r = .89), and both assessments
      discriminated across pain severity levels (P < .001, RV = .95). Patients'
      evaluations of the CHRONIC PAIN-CAT were favorable. PERSPECTIVE: This report
      demonstrates that the CHRONIC PAIN-CAT is feasible for administration in a
      clinic. The application has the potential to improve pain assessment and help
      clinicians manage chronic pain.

PMID- 19595639
TI  - Opioid prescribing practices in chronic pain management: guidelines do not
      sufficiently influence clinical practice.
AB  - To examine the use of extended-release (ER) opioids relative to immediate-release
      (IR) opioids in chronic opioid prescription episodes, pharmacy claim data from a
      national health plan database were analyzed. Enrollees having at least 1 pharmacy
      claim for an opioid formulation between June 2003 and May 2006, and at least 1
      year of continuous enrollment after their first observed pharmacy claim were
      included. Opioid prescription episodes were created by combining contiguous days
      of therapy, allowing for a maximum of 7 days between refills (>or=8 d = new
      episode). Outcomes are reported in the form of probabilities and odds ratios
      (ORs). A total of 3,993,011 opioid prescription episodes were derived from
      1,967,898 enrollees. Overall, prescription episodes involving IR preparations
      (97.7%) were more prevalent than episodes using ER preparations (2.3%). The odds
      of an ER preparation being prescribed chronically (>or=60 d) were approximately
      11 times that of an IR preparation (OR = 10.7); however, the majority of chronic
      prescription episodes used IR formulations (84.8%). When stratified by prescriber
      type (specialist vs nonspecialists), the probability of a specialist prescribing
      ER opioids in these chronic prescription episodes was 19.1% versus 13.7% for
      nonspecialists. Specialists were about 50% more likely to prescribe ER opioids
      relative to nonspecialists (OR = 1.49). PERSPECTIVE: This analysis suggests that
      the availability of pain-treatment guidelines, recommendations, and education
      alone may not be enough to influence opioid-prescribing practices in the
      treatment of chronic pain.

PMID- 19595640
TI  - Both happy and sad melodies modulate tonic human heat pain.
AB  - The mechanism of music effects on pain perception remains to be elucidated. To
      determine which component (mood or valence) of music is more important in music
      induced hypoalgesia, we compared the effects of 2 melodies with different moods
      (happy vs sad) but with the same degree of valence (pleasant vs unpleasant) to an
      affective neutral lecture and a control (baseline) on the objective and
      subjective responses to tonic heat pain. Our hypothesis was that if mood was the
      key component, the happy melody would reduce pain, whereas the sad one would
      exacerbate pain; and if valence is the key component, the 2 melodies would both
      alleviate pain. Twenty females participated in this study which consisted of 4
      conditions (baseline, happy melody, sad melody, and lecture). Pain tolerance time
      (PTT), pain intensity, and distress dynamics and the characteristics of pain were
      measured. A newly devised multiple affective rating scale (MARS) was employed to
      assess the subjective experience of auditory perception. Both happy and sad
      melodies of equal valence resulted in significant lower pain ratings during the
      pain test and were in contrast to the mood prediction. These results indicate
      that the valence of music, rather than the mood it induced, appears to be the
      most likely mediator of the hypoalgesic effect of the different music.
      PERSPECTIVE: This article provides new evidence that the valence of music is more
      crucial than mood in affective pain modulation. This finding gives impetus for
      health professionals to manage pain more effectively in patients with proper
      music.

PMID- 19595641
TI  - Continuous buprenorphine delivery effect in streptozotocine-induced painful
      diabetic neuropathy in rats.
AB  - Diabetic peripheral neuropathy (DPN) can induce loss of nociception as well as
      mechanical hyperalgesia and tactile allodynia. Pharmacological and clinical
      studies have shown that buprenorphine, a low-molecular-weight, lipophilic, opioid
      analgesic available as a transdermal matrix patch formulation, acts on
      neuropathic pain. To assess the role of buprenorphine in the treatment of DPN
      associated neuropathic pain, we used a well-established experimental rat model of
      DPN in which buprenorphine at doses of 1.2 and 2.4 microg/kg/h was administered
      by implantable Alzet osmotic pumps for 3 weeks. After 6 weeks of diabetes, nerve
      conduction velocity (NCV) and behavioural responses to noxious mechanical and
      thermal stimuli were assessed. Diabetic rats showed an impairment of NCV,
      mechanical allodynia, and thermal hypoalgesia. Both doses of buprenorphine
      significantly reversed the diabetes-induced allodynia up to day 7 of treatment.
      Buprenorphine did not alter either thermal perception or NCV. PERSPECTIVE: This
      study evaluated, through a multimodal approach, the analgesic effect of
      buprenorphine in an experimental rat model of painful DPN. Our results suggest a
      possible role for buprenorphine in the management of DPN-associated neuropathic
      pain.

PMID- 19595643
TI  - Advanced design of electron-transfer pathways across biomolecular interfaces,
      dedicated to Professor Lo Gorton. Editorial.

PMID- 19595644
TI  - Label-free and amplified quantitation of proteins in complex mixtures using
      diffractive optics technology.
AB  - Immunoaffinity approaches remain invaluable tools for characterization and
      quantitation of biopolymers. Their application in separation science is often
      limited due to the challenges of immunoassay development. Typical end-point
      immunoassays require time consuming and labor-intensive approaches for
      optimization. Real-time label-free analysis using diffractive optics technology
      (dot) helps guide a very effective iterative process for rapid immunoassay
      development. Both label-free and amplified approaches can be used throughout
      feasibility testing and ultimately in the final assay, providing a robust
      platform for biopolymer analysis over a very broad dynamic range. We demonstrate
      the use of dot in rapidly developing assays for quantitating (1) human IgG in
      complex media, (2) a fusion protein in production media and (3) protein A
      contamination in purified immunoglobulin preparations.

PMID- 19595642
TI  - Effects of oxytocin and prolactin on stress-induced bladder hypersensitivity in
      female rats.
AB  - Anecdotal evidence suggests that chronic bladder pain improves while
      breastfeeding. The present study sought to identify potential mechanisms for such
      a phenomenon by investigating the effects of the lactogenic hormones prolactin
      (PL) and oxytocin (OXY) in a rat model of bladder nociception. Lactating rats
      were less sensitive to urinary bladder distension (UBD) than controls. In
      investigating potential antinociceptive and anxiolytic roles for these hormones,
      we found exposure to a footshock paradigm (STRESS groups) produced bladder
      hypersensitivity in saline-treated rats, manifested as significantly higher
      electromyographical (EMG) responses to UBD, compared to rats exposed to a
      nonfootshock paradigm (SHAM groups). This hypersensitivity was attenuated by the
      intraperitoneal administration of OXY prior to footshock in the STRESS-OXY group.
      The administration of PL augmented EMG responses in the SHAM-PL group but had no
      effect on the responses of the STRESS-PL group. In the absence of behavioral
      pretreatment, OXY attenuated UBD-evoked responses while PL had no effect.
      Moreover, OXY-treated rats spent more time in the open arm of an elevated plus
      maze compared to saline-treated rats suggesting anxiolysis. These studies suggest
      the potential for systemic OXY, but not PL, as an analgesic and anxiolytic
      treatment for painful bladder disorders such as interstitial cystitis.
      PERSPECTIVE: This study presents evidence that systemic oxytocin has both
      analgesic and anxiolytic properties which may make it a potentially useful agent
      for patients with stress-exacerbated chronic-pain syndromes such as interstitial
      cystitis. These studies do not suggest a similar role for prolactin.

PMID- 19595645
TI  - Time resolved analysis of risperidone and 9-hydroxy-risperidone in hair using
      LC/MS-MS.
AB  - Risperidone (RSP) is a second generation anti-psychotic drug used for the
      treatment of schizophrenia and anxiety disorders. In the last decades, clinical
      applications of hair analysis have received an increasing attention, because of
      its wide surveillance window. In this work, we describe a simple and fast method
      for detection and quantification of RSP and its major metabolite, 9-OH
      risperidone (9-OH-RSP), in human hair. The validated method (cv of interday
      precision, intraday precision and accuracy<15%, r(2) of the calibration
      curves>0.98, limit of detection (LOD) was 0.90 pg/mg hair (RSP) and 1.52 pg/mg
      hair (9-OH-RSP), the lower limit of quantification (LLOQ) were 1.8 and 4.56
      pg/mg, respectively, extraction yield were 86.9% for RSP and 86.7% for 9-OH-RSP)
      was successfully applied to quantify both substances in the hair of psychiatric
      patients treated with RSP. After washing, pulverisation, incubation in an
      ultrasound bath and liquid/liquid extraction of the hair samples, quantification
      was performed using LC/MS-MS in selected reaction monitoring mode with
      methaqualone as internal standard. Concentrations for RSP and its major
      metabolite ranged from 36 to 4765 pg/mg and from 14 to 57 pg/mg, respectively in
      the different hair segments. These preliminary results indicate a better
      relationship between the administered dose and hair concentration for 9-OH-RSP
      than for the parent drug. Furthermore, the RSP/9-OH-RSP ratio varied from 1 to
      83.

PMID- 19595646
TI  - GC-MS analysis of S-nitrosothiols after conversion to S-nitroso-N-acetyl cysteine
      ethyl ester and in-injector nitrosation of ethyl acetate.
AB  - S-Nitrosothiols from low-molecular-mass and high-molecular-mass thiols, including
      glutathione, albumin and hemoglobin, are endogenous potent vasodilators and
      inhibitors of platelet aggregation. By utilizing the S-transnitrosation reaction
      and by using the lipophilic (pK(L) 0.78) and strong nucleophilic synthetic thiol
      N-acetyl cysteine ethyl ester (NACET) we have developed a GC-MS method for the
      analysis of S-nitrosothiols and their (15)N- or (2)H-(15)N-labelled analogs as S
      nitroso-N-acetyl cysteine ethyl ester (SNACET) and S(15)NACET or d(3)-S(15)NACET
      derivatives, respectively, after their extraction with ethyl acetate. Injection
      of ethyl acetate solutions of S-nitrosothiols produced two main reaction
      products, compound X and compound Y, within the injector in dependence on its
      temperature. Quantification was performed by selected-ion monitoring of m/z 46
      (i.e., [NO(2)](-)) for SNACET and m/z 47 (i.e., [(15)NO(2)](-)) for
      S(15)NACET/d(3)-S(15)NACET for compound X, and m/z 157 for SNACET and m/z 160 for
      d(3)-S(15)NACET for compound Y. In this article we describe the development,
      validation and in vitro and in vivo applications of the method to aqueous
      buffered solutions, human and rabbit plasma. Given the ester functionality of
      SNACET/S(15)NACET/d(3)-S(15)NACET, stability studies were performed using metal
      chelators and esterase inhibitors. The method was found to be suitable for the
      quantitative determination of various S-nitrosothiols including SNACET externally
      added to human plasma (0-10microM). Nitrite contamination in ethyl acetate was
      found to interfere. Our results suggest that the concentration of endogenous S
      nitrosothiols in human plasma does not exceed about 200nM in total. Oral
      administration of S(15)NACET to rabbits (40-63micromol/kg body weight) resulted
      in formation of ALB-S(15)NO, [(15)N]nitrite and [(15)N]nitrate in plasma.

PMID- 19595647
TI  - Breath acetone analysis with miniaturized sample preparation device: in-needle
      preconcentration and subsequent determination by gas chromatography-mass
      spectroscopy.
AB  - A new approach to the determination of human breath acetone with particle-packed
      sample preparation needle was developed. The extraction needle was packed with a
      copolymer of methacrylic acid and ethylene glycol dimethacrylate as the
      extraction medium. For the analysis of breath sample, exhaled breath was
      collected in a sampling bag, and 50 mL of the breath sample was extracted with
      the needle-type sample preparation device followed by analysis using gas
      chromatography-mass spectrometry (GC-MS). After the optimization of several basic
      extraction conditions for standard acetone samples, breath acetone concentration
      taken from controlled type-2 diabetic patients was determined. Furthermore, time
      variations of breath and urine acetone of four healthy individuals under fasting
      conditions were measured. Urine sample was collected in glass vial, and urine
      acetone concentration was also determined with the extraction needle by analyzing
      the corresponding headspace gas. The results demonstrated that the particle
      packed extraction needle showed an excellent extraction performance for acetone
      in both breath and urine headspace samples, and that there is a clear correlation
      between the concentration of breath acetone and HbA1c level of controlled type-2
      diabetic patients. The breath acetone level in controlled diabetic patients was
      in the range between 0.19 and 0.66 ppmv, where its concentration in medically
      untreated type-2 patient was 0.92 and 1.20 ppmv. The breath acetone concentration
      in healthy male was increased to 5.66 ppmv under the 24 h of fasting test, and a
      high correlation between the breath and urine acetone concentration was also
      observed. On the basis of the above results, the potential applications of the
      proposed method to the diagnosis of diabetes and/or ketoacidosis were suggested.

PMID- 19595648
TI  - Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa
      for outcome prediction in patients with acute decompensated hepatitis.
AB  - BACKGROUND AND AIM: The model for end-stage liver disease (MELD) is used to
      predict the outcome of patients with cirrhosis. Incorporation of serum sodium
      (Na) into MELD may further increase its prognostic ability. Two Na-containing
      MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability.
      This study compared the predictive accuracy of these models for acute
      decompensated hepatitis. METHODS: We investigated the outcome of 182 patients
      with acute decompensated hepatitis. RESULTS: Twenty (11%) patients died at 3
      months. The MELD-Na and MELDNa both had significantly higher area under the
      receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na:
      0.908, MELDNa: 0.895, MELD: 0.823, p=0.004 and 0.001, respectively). Among 96
      patients without specific antiviral treatment, the MELD-Na and MELDNa
      consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa:
      0.882, MELD: 0.810, p=0.008 and 0.004, respectively). Three independent
      indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence
      interval [CI]: 1.72-18.7), serum albumin<3.7 g/dL (OR: 5.68, 95% CI: 1.18-27.03)
      and serum sodium (Na)<138 mequiv./L (OR: 10.0, 95% CI: 2.08-47.62), were
      associated with 3-month mortality. CONCLUSION: MELD-Na and MELDNa provide better
      prognostic accuracy than the MELD for patients with acute decompensated
      hepatitis. The adequacy of liver reserve determines the outcome of these
      patients.

PMID- 19595650
TI  - Reply to: Free-style local perforator flaps: concept and classification system.
      JPRAS 2009;62(5):602-609.

PMID- 19595651
TI  - Junior plastic surgeon's confidence in aesthetic surgery practice: a comparison
      of two didactic systems.
AB  - The importance of residents' training in aesthetic surgery and the need for
      acquiring confidence in performing cosmetic procedures is an established
      knowledge. A survey was done in two different training systems to evaluate the
      experience of junior plastic surgeons in performing four common aesthetic surgery
      procedures at the end of their residency. The first system guarantees a
      theoretical background and a certain number of aesthetic procedures to be
      performed by the trainee, in contrast to the second system where mainly
      theoretical knowledge in cosmetic surgery is warranted to residents. The
      residents' comfort in performing specific operations was quite varied between the
      two systems. The comparison showed that junior plastic surgeons reached a higher
      degree of self-confidence in aesthetic practice in system A when compared to
      system B. The similarities and differences between the two systems are analysed
      and discussed. The possibility of reforming residency programmes by following the
      structure and the philosophy of system A is proposed.

PMID- 19595649
TI  - [Usefulness of Clinical Risk Index for Babies based on birth weight in predicting
      hospital death and severe intraventicular hemorrhage in the SEN 1500 Spanish
      neonatal network].
AB  - OBJECTIVE: To evaluate the usefulness of the Clinical Risk Index for Babies
      (CRIB) in predicting hospital mortality and severe intraventricular hemorrhage
      (IVH) in very low birth weight infants stratified by weight groups, in the
      Spanish neonatal network SEN 1500. PATIENTS AND METHODS: A prospective cohort
      study was made. Morbidity-mortality data and CRIB were collected in newborns
      weighing below 1500 g and admitted to 68 neonatal intensive care units between
      January 2002 and December 2006. Data were analyzed globally and stratified by
      weight groups (< 501 g, 500-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g).
      Multivariate models were generated and ROC curves were plotted for estimating
      predictive values. RESULTS: A total of 10,608 patients were analyzed. The mean
      weight was 1116 g (SD 267), and gestational age 29.5 weeks (SD 2.9). Low birth
      weight for gestational age was 34.3% and the multiple birth rate 36%. Prenatal
      corticoids were given in 78.2%. Severe intraventricular hemorrhage was diagnosed
      in 8.5%. Gender, prenatal corticoids, birth weight, gestational age and CRIB
      proved significant for the outcomes. CRIB showed the highest predictive accuracy
      in all strata (P < 0.001) except in the 501-750 g group, where it was similar to
      gestational age. Body weight showed the lowest AUC in all groups, except in the
      1251-1500 g group, where it was no different to gestational age. Gestational age
      and CRIB yielded greater AUC values than weight (P < 0.001) in all groups. No
      significant differences were found between CRIB and gestational age, except in
      the 751-1000 g group, where gestational age was greater (P = 0.029). CONCLUSIONS:
      The CRIB is the best predictor among newborns below 1500 g, except in the 501-750
      g group, where CRIB is similar to gestational age. Body weight is the worst
      predictor, except in the group 1251-1500 g, where it is similar to gestational
      age. The accuracies of CRIB and gestational age in the prediction of IVH are
      similar, and both superior to body weight. This similarity persists in all the
      groups, except in the 751-1000 g interval, where gestational age is a better
      predictor.

PMID- 19595652
TI  - Earlobe reconstruction following plug and tunnel piercing.

PMID- 19595653
TI  - Patient support groups for facial disfigurements.

PMID- 19595654
TI  - Descending the reconstructive ladder with tube pedicles.

PMID- 19595655
TI  - Reconstruction of vulva using pudendal thigh gluteal fold bilobed flap.
AB  - In reconstructing a large defect of the vulva, we combined the gluteal fold and
      the pudendal thigh flaps and made a bilobed flap. Using this gluteal fold
      pudendal thigh bilobed flap, we reconstructed a vagina with sufficient depth and
      width. The surrounding skin defect was simultaneously reconstructed. Sensation
      was intact in all areas of the reconstruction. In addition, the sutured lines of
      both donor sites are hidden in the gluteal and inguinal folds. Thus, the gluteal
      fold pudendal thigh bilobed flap seems to be ideal for reconstructing large
      vulvar defects.

PMID- 19595656
TI  - HIT II--an underestimated complication in reconstructive microsurgery?

PMID- 19595657
TI  - Treatment of the severe or recurrent inverted nipple by interposition of a
      resorbable polydioxanone sheet.

PMID- 19595659
TI  - Superficial femoral artery injury resulting from intertrochanteric hip fracture
      fixation by a locked intramedullary nail.
AB  - Iatrogenic vascular injuries are uncommon during the course of proximal femur
      surgical procedures. We report the case of an 85-year-old female presenting with
      an intertrochanteric fracture, treated by anterograde (cephalocondylic)
      intramedullary nailing (Stryker gamma 3 nail) and complicated by a superficial
      femoral artery laceration at the level of the distal locking screw. Lower limb
      traction in adduction and internal rotation on the operating table might put at
      risk the superficial femoral artery during distal screw drilling and insertion.
      We therefore recommend returning to the neutral position and reducing lower
      extremity traction after femoral head screw placing and before final distal screw
      insertion. This technical precaution should limit the risk of superficial femoral
      artery injury associated with short-nail anterograde intramedullary nailing. TYPE
      OF STUDY: Level IV retrospective.

PMID- 19595658
TI  - WNT and BMP signaling are both required for hematopoietic cell development from
      human ES cells.
AB  - Pluripotent human embryonic stem (hES) cells are capable of generating a variety
      of mature cell types, including hematopoietic cells in vitro. However, the
      precise signaling mechanisms that regulate hematopoietic cell development from
      hES cells are still poorly documented. Here we demonstrate that hemoangiogenic
      cells derived from hES cells are defined by their high-level expression of KDR
      and low-level expression of PDGFRalpha (KDR(+)PDGFRalpha(lo)), and that the
      generation of such cells from hES cells is significantly elevated by the addition
      of WNT3a or BMP4 during differentiation. The addition of WNT3a caused the
      induction of both hemogenic and angiogenic activities, and the addition of BMP4
      preferentially increased angiogenic activity, all enriched in the
      KDR(+)PDGFRalpha(lo) cell fraction. Interestingly, WNT3a stimulation of
      hemoangiogenic cell genesis was virtually abolished in the presence of a BMP
      inhibitor. On the other hand, the BMP4-induced angiogenic cell genesis was
      suppressed by coaddition of a WNT inhibitor. Thus, WNT and BMP signaling
      coordinately direct the differentiation of hES cells into KDR(+)PDGFRalpha(lo)
      hemoangiogenic cells.

PMID- 19595660
TI  - Inter- and intrapopulational genetic variability of Tityus serrulatus
      (Scorpiones, Buthidae).
AB  - In Brazil, there are near 20 genera and almost 120 species of scorpions of which
      95% reproduce sexually. Parthenogenetic reproduction, however, may also take
      place. To gain insight into useful molecular markers in parthenogenetic scorpion
      species, we studied DNA polymorphism using two molecular approaches: simple
      sequence repeat anchored polymerase chain reaction (SSR-PCR) and sequencing of
      the cytochrome C oxidase subunit I of the mitochondrial genome, mtDNA (COXI), of
      Tityus serrulatus. Three different groups were used: group 1, composed of 1
      female and 14 descendants; group 2 with 1 female and 17 descendants, both from
      the city of Uberlandia, State of Minas Gerais (MG), Brazil, and the third group
      that consisted of three adult scorpions from the city of Belo Horizonte, MG. The
      profiles generated by SSR-PCR were identical for all specimens, while partial
      sequencing of COXI showed the presence of SNPs. After aligning COXI contigs, one
      of the groups presented 18 SNPs and the second 8 SNPs. The two groups were
      differentiated by two diagnostic SNPs. We did not find evidence of mitochondrial
      recombination. The results are in agreement with the parthenogenetic mode of
      reproduction of this species and sequencing of the COXI gene enabled the
      separation of scorpions groups.

PMID- 19595661
TI  - Molecular phylogeography of Culex quinquefasciatus mosquitoes in central
      Bangladesh.
AB  - Mosquitoes in the Culex pipiens complex are a major vector of numerous parasitic
      and arboviral diseases. Here we report the phylogeography of a prevalent Culex
      mosquito, Cx. quinquefasciatus, from three locations in Bangladesh: Dhaka, Savar
      and Mymensingh. Sequence analysis of the genes encoding mitochondrial cytochrome
      oxidase subunit II, nuclear elongation factor-1 alpha, and acetylcholinesterase-2
      revealed the lack of a population genetic structure among the three locations.
      Moreover, the highly divergent ribosomal internal transcribed spacer 2 suggests
      that this locus has not evolved in concert. The results further show evidence of
      historical introgression of internal transcribed spacer 2 from Cx. pipiens to Cx.
      quinquefasciatus of Bangladesh, and that the introgression occurred before Cx.
      quinquefasciatus had dispersed within this region. The study also reveals
      historical population expansion in this region, followed by a post-expansion
      Wolbachia sweep.

PMID- 19595663
TI  - An outbreak of enterotoxaemia at livestock farm during subtropical summer.
AB  - Present investigations were carried out on 10 dead animals including eight in
      lambs, one in goat kid and one in calf during subtropical summer at a local farm.
      The weather was hot and humid with rain occurring during the period. The history
      suggests an association of weather and concentrate/lush green diet/fodder with
      occurrence of the disease. The most consistent clinical signs reported were no
      interest in feeding, herding in a corner with head down, diarrhea of low degree
      and temperature around 102 degrees F. At postmortem examination, the most
      consistent findings were swollen soft kidneys, hydropericardium, congested and
      edematous lungs, congested liver, myocardial hemorrhages and ballooning of
      intestines. The histopathological examination revealed the most striking changes
      in kidney of vacuolation in renal tubular epithelial cells and increased Bowman's
      space in the glomeruli. The histopathological examination of liver revealed
      congestion. Lungs revealed congestion and edema. The urine from urinary bladder
      collected showed high glucose. The deaths in these animals were probably due to
      enterotoxaemia type D.

PMID- 19595662
TI  - Eye disease related to onchocerciasis: a clinical study in the Aratha-u, Yanomami
      Tribe, Roraima State, Brazil.
AB  - The prevalence of ocular lesions due to onchocerciasis was evaluated among
      residents of the Yanomami Tribe, in the northern Amazon, Brazil, an endemic area
      for onchocerciasis. 83 natives were submitted to an ocular examination including
      an external examination, biomicroscopy, intraocular pressure measurement, and a
      fundus examination. Clinical, parasitological and serological tests were carried
      out simultaneously. The population demonstrated a high prevalence of
      eosinophilia, skin microfilaria (55%) and onchocercal subcutaneous nodules (35%).
      A high prevalence of probable onchocerciasis related eye lesions was detected.
      Punctate keratitis (41%) and microfilaria in the anterior chamber (39%) were
      found as well as other probable onchocercotic lesions-chorioretinitis (7.2%) and
      anterior uveitis (6.0%). Other anterior eye lesions (corneal leucomas,
      conjunctival injection, lid nodules) occurred in 51% of the individuals. The
      anterior eye lesions were more prevalent than the posterior lesions. We did not
      find an association of glaucoma with onchocerciasis. The prevalence of these
      suggestive ocular lesions strongly correlates with the cutaneous nodules and
      eosinophilia, suggesting that skin nodules may be an indication for an eye
      examination. The present study provides evidence that significant infection and
      eye disease due to onchocerciasis persists in certain regions of Northern South
      America.

PMID- 19595664
TI  - Canine visceral leishmaniasis: asymptomatic infected dogs as a source of L.
      infantum infection.
AB  - Clinically infected dogs have been identified as the main reservoir hosts of
      visceral leishmaniasis (VL) caused by Leishmania infantum in the Mediterranean
      region. The objective of this study was to determine the potential of
      asymptomatic infected dogs compared with symptomatic ones as a source of L.
      infantum infection to golden hamster. For this purpose, anti-Leishmania
      antibodies were detected with direct agglutination test (DAT) in 13 symptomatic
      (7 seropositive =>or=1:320) and 53 asymptomatic (9 seropositive =>or=1:320 and 44
      seronegative =<1:320) ownership dogs. DNA of Leishmania sp. was extracted from
      skin and peripheral blood tissues of each dog and tested by PCR. Sixty-six Syrian
      golden hamsters (Mesocricetus auratus) were used for the determination of
      infectivity and pathogenicity of L. infantum, isolated from the dogs. We used the
      internal transcribed spacer 2 (ITS 2) rDNA sequence analysis. The results showed
      that 22 and 11 out of 66 inoculated golden hamsters were positive by PCR and
      parasitological examinations, respectively. From 22 PCR positive hamsters, 17
      were related to asymptomatic dogs and 5 were from symptomatic ones. There was no
      significant difference between symptomatic and asymptomatic dogs in producing
      Leishmania infection in the susceptible animal model (P=0.66). Smears and
      cultures of 5 dogs from 13 symptomatic dogs (38.5%) and 6 dogs from 53
      asymptomatic ones (11.3%) were found to be positive at parasitological
      examination. All the L. infantum isolates from symptomatic and asymptomatic dogs
      were similar in sequencing. In conclusion, asymptomatic infected dogs as well as
      symptomatic ones can harbor L. infantum in their blood and skins which are
      virulent and infectious for inoculated golden hamster.

PMID- 19595665
TI  - Variations in the mitochondrial DNA markers in the Anopheles (Cellia) sundaicus
      population from the Andaman and Nicobar Islands, India.
AB  - Four sibling species in the Anopheles sundaicus complex have earlier been
      reported, including species D from the Andaman and Nicobar Islands of India where
      it constitutes 58% of all Anopheles population and is a major malaria vector.
      Earlier, we have reported the identical sequences for ribosomal DNA markers among
      the specimens of A. sundaicus from Andaman and Nicobar islands irrespective of
      their habitat. These ITS2 sequences were also identical to the reported sequence
      of variant III of Southeast Asian A. sundaicus. In the present study, we describe
      variations in three mitochondrial DNA markers among these specimens from Andaman
      and Nicobar islands. There were two different genotypes for each locus of COI and
      COII, and three genotypes for cytochrome-b (Cyt-b) locus resulting in three
      different combined genotypes (genotypes I, II and III) in the population.
      Specimens with combined genotype I (59%, n=100) were found only among the A.
      sundaicus population breeding in fresh water whereas two different multi-loci
      genotypes i.e. genotype II (25%, n=100) and genotype III (16%, n=100) were
      present in the population breeding in brackish water. Thus, the A. sundaicus
      population breeding in fresh water was homogenous with single multi-loci genotype
      and can be distinguished from the heterogenous mosquito population breeding in
      brackish water with these markers. These Cyt-b and COI sequences of A. sundaicus
      species D were also different from the reported Southeast Asian species of A.
      sundaicus.

PMID- 19595666
TI  - Nanoparticles evading the reticuloendothelial system: role of the supported
      bilayer.
AB  - We have previously shown that the PEGylated LPD (liposome-polycation-DNA)
      nanoparticles were highly efficient in delivering siRNA to the tumor with low
      liver uptake. Its mechanism of evading the reticuloendothelial system (RES) is
      reported here. In LPD, nucleic acids were condensed with protamine into a compact
      core, which was then coated by two cationic lipid bilayers with the inner bilayer
      stabilized by charge-charge interaction (also called the supported bilayer).
      Finally, a detergent-like molecule, polyethylene glycol (PEG)-phospholipid is
      post-inserted into the lipid bilayer to modify the surface of LPD. The dynamic
      light scattering (DLS) data showed that LPD had improved stability compared to
      cationic liposomes after incubation with a high concentration of DSPE-PEG(2000),
      which is known to disrupt the bilayer. LPD prepared with a multivalent cationic
      lipid, DSGLA, had enhanced stability compared to those containing DOTAP, a
      monovalent cationic lipid, suggesting that stronger charge-charge interaction in
      the supported bilayer contributed to a higher stability. Distinct nanoparticle
      structure was found in the PEGylated LPD by transmission electron microscopy,
      while the cationic liposomes were transformed into tubular micelles. Size
      exclusion chromatography data showed that approximately 60% of the total cationic
      lipids, which were located in the outer bilayer of LPD, were stripped off during
      the PEGylation; and about 20% of the input DSPE-PEG(2000) was incorporated into
      the inner bilayer with about 10.6 mol% of DSPE-PEG(2000) presented on the
      particle surface. This led to complete charge shielding, low liver sinusoidal
      uptake, and 32.5% injected dose delivered to the NCI-H460 tumor in a xenograft
      model.

PMID- 19595667
TI  - Evidence of phosphatidylethanolamine and phosphatidylglycerol presence at the
      annular region of lactose permease of Escherichia coli.
AB  - Biochemical and structural work has revealed the importance of phospholipids in
      biogenesis, folding and functional modulation of membrane proteins. Therefore,
      the nature of protein-phospholipid interaction is critical to understand such
      processes. Here, we have studied the interaction of 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3
      [phospho-rac-(1-glycerol)] (POPG) mixtures with the lactose permease (LacY), the
      sugar/H(+) symporter from Escherichia coli and a well characterized membrane
      transport protein. FRET measurements between single-W151/C154G LacY reconstituted
      in a lipid mixture composed of POPE and POPG at different molar ratios and pyrene
      labeled PE or PG revealed a different phospholipid distribution between the
      annular region of LacY and the bulk lipid phase. Results also showed that both PE
      and PG can be part of the annular region, being PE the predominant when the PE:PG
      molar ratio mimics the membrane of E. coli. Furthermore, changes in the
      thermotropic behavior of phospholipids located in this annular region confirm
      that the interaction between LacY and PE is stronger than that of LacY and PG.
      Since PE is a proton donor, the results obtained here are discussed in the
      context of the transport mechanism of LacY.

PMID- 19595668
TI  - Nuclear protein IkappaB-zeta inhibits the activity of STAT3.
AB  - STAT3 (Signal transducer and activator of transcription 3) is a key transcription
      factor of the JAK-STAT (Janus kinase/signal transducer and activator of
      transcription) pathway that regulates cell proliferation and apoptosis.
      Activation of STAT3 is under tight regulation, and yet the different signaling
      pathways and the mechanisms that regulate its activity remain to be elucidated.
      Using a yeast two-hybrid screening, we have identified a nuclear protein IkappaB
      zeta that interacts in a novel way with STAT3. This physical interaction was
      further confirmed by co-immunoprecipitation assays. The interaction regions were
      mapped to the coiled-coil domain of STAT3 and the C-terminal of IkappaB-zeta.
      Overexpression of IkappaB-zeta inhibited the transcriptional activity of STAT3.
      It also suppressed cell growth and induced cell apoptosis in SRC-simulated cells,
      which is partially mediated by down-regulation of expression of a known STAT3
      target gene, MCL1. Our results suggest that IkappaB-zeta is a negative regulator
      of STAT3, and demonstrate a novel mechanism in which a component of the NF-kappaB
      signaling pathway inhibits the activation of STAT3.

PMID- 19595669
TI  - Aspirin induces apoptosis through the blockade of IL-6-STAT3 signaling pathway in
      human glioblastoma A172 cells.
AB  - Aspirin has been reported to induce apoptosis in various cancer cell lines.
      However, the apoptotic effects of aspirin on human brain tumor cells are not well
      understood. Here, we have assessed the effect of aspirin on human gliobalstoma
      cell line A172 and found that aspirin induced the apoptosis of A172 cells, as
      determined by TUNEL assay, FACS analysis, and Hoechst staining. The underlying
      mechanism of this effect consists of reduction in the level of phosphorylated
      STAT3 (Tyr705), a transcription factor required for survival of A172 cells.
      Moreover, the expression of STAT3 target genes such as Cyclin D1, XIAP, and Bcl-2
      that are essential for cell growth and survival was apparently attenuated after
      aspirin treatment. We also showed that the expression and secretion of
      interleukin-6 (IL-6), leading to STAT3 phosphorylation, was inhibited by aspirin.
      When administered exogenous IL-6 to aspirin-treated A172 cells, the
      phosphorylation of STAT3 and cellular apoptosis were restrained compared to
      aspirin only-treated cells. Taken together, our results indicate that aspirin
      causes apoptosis via down-regulation of IL-6-dependent STAT3 signaling,
      suggesting that aspirin could be therapeutically useful for a potential anti
      glioblastoma therapeutic approach.

PMID- 19595670
TI  - Switches in 6-phosphofructo-2-kinase isoenzyme expression during rat sperm
      maturation.
AB  - Here we analyzed Pfkfb3 and Pfkfb4 gene expression in rat testis development,
      isolated testicular cells and spermatozoa. Real time RT-PCR analysis during
      testis development showed the maximum expression of Pfkfb3 in pre-puber samples
      and of Pfkfb4 in adult samples. Western blot analysis showed that uPFK-2 protein,
      a product of Pfkfb3 gene, was present in all the cell types forming the
      seminiferous epithelium (Sertoli, interstitial and spermatogenic cells). In
      contrast, tPFK-2, a product of Pfkfb4 gene, was restricted to spermatogenic
      cells. Confocal analyses by indirect immunofluorescence also corroborated this
      expression pattern. Immunoblotting studies of isolated spermatozoa demonstrated
      the presence of uPFK-2 only in immature sperm and once spermatozoa became fully
      functional this isozyme was replaced by the testicular isozyme tPFK-2. Moreover,
      immunostaining confirmed that tPFK-2 was localized mainly in the acrosomal region
      of the sperm head and in the mid-piece of the flagellum, where other
      spermatogenic cell-specific glycolytic enzymes have been found.

PMID- 19595671
TI  - NADPH oxidase activity in allergenic pollen grains of different plant species.
AB  - Pollen is an important trigger of allergic diseases. Recent studies have shown
      that ragweed pollen NAD(P)H oxidase generates reactive oxygen species (ROS) and
      plays a prominent role in the pathogenesis of allergies in mouse models. Here, we
      demonstrated that allergenic pollen grains showed NAD(P)H oxidase activity that
      differed in intensity and localization according to the plant families. The
      activity occurred at the surface or in the cytoplasm in pollen of grasses, birch,
      and ragweed; in subpollen particles released from ragweed pollen; and at the
      inner surface or in the cytoplasm but not on the outer wall, which was sloughed
      off after the rupture, of pollen of Japanese cedar and Japanese cypress. The
      activity was mostly concentrated within insoluble fractions, suggesting that it
      facilitates the exposure of tissues to ROS generated by this enzyme. The extent
      of exposure to pollen-generated ROS could differ among the plant families.

PMID- 19595672
TI  - Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the
      brains of EAE rats.
AB  - Ninjurin1 (nerve injury-induced protein, Ninj1) is an adhesion molecule that is
      essential for cell-to-cell interactions. However, little is known about the
      function of Ninj1 in the central nervous system (CNS). To address its role in the
      CNS, we analyzed the expression pattern of Ninj1 in normal rats and in an
      experimental autoimmune encephalomyelitis (EAE) model. Ninj1 was expressed in
      three major compartments of brains, meninges, the choroid plexus, and parenchymal
      perivascular spaces. In the EAE brains, Ninj1 was strongly expressed in myeloid
      cells (macrophages/monocytes and neutrophils) and partially expressed in
      endothelial cells (ECs). Furthermore, Ninj1 enhanced adhesion between BV2 cells
      (murine monocyte lineage microglia) and HBMECs (human brain microvascular
      endothelial cells). Collectively, our findings suggest that Ninj1 may mediate the
      entry of myeloid cells into the CNS in normal and EAE brains, and it is a
      potential therapeutic target for regulating myeloid cell trafficking across the
      blood-brain barrier (BBB) in CNS immune processes.

PMID- 19595673
TI  - Omentopexy enhances graft function in myocardial cell sheet transplantation.
AB  - Myocardial cell sheets (MCS) are a potentially valuable tool for tissue
      engineering aimed at heart regeneration. Several methods have recently been
      established for the fabrication of MCS. However, the lack of a sufficient blood
      supply has inhibited functional recovery of the MCS. To address this challenge,
      we combined MCS transplantation with omentopexy (OP), which utilizes omental
      tissue as a surgical flap. Rats were divided into five groups: sham, myocardial
      infarction (MI), MCS transplantation, OP, and MCS+OP. Histologic analysis
      revealed that MCS+OP drastically reversed MI-induced cardiac remodeling.
      Echocardiography revealed that MCS increased cardiac function, while OP had a
      synergistic beneficial effect with MCS transplantation. Immunofluorescence
      imaging showed that OP increased the survival of transplanted cardiomyocytes, and
      increased the blood supply through enhancement of angiogenesis and migration of
      small arteries into the MCS. Taken together, we concluded that OP is a promising
      strategy for the enhancement of graft function in MCS transplantation.

PMID- 19595674
TI  - Decreased cell proliferation in the dentate gyrus does not associate with
      development of anhedonic-like symptoms in rats.
AB  - Depressive disorders have been proposed to be caused by stress-induced down
      regulation of hippocampal neurogenesis. Nevertheless, several reports have
      recently pointed out that, in rodent models of depression, suppression of
      generation of new hippocampal neurons is not by itself sufficient to induce the
      development of depression-related symptoms. In the present study, we used the
      cell proliferation blocker methylazoxymethanol (MAM) and the rat chronic mild
      stress (CMS) model of depression to challenge the neurogenic theory of
      depression. In order to achieve a comparable reduction in hippocampal
      cytogenesis, rats were either chronically treated with MAM for 2 weeks, or
      subjected to an 8 week regime of chronic mild stress. Consumption of a palatable
      sucrose solution was monitored once a week to assess the development of anhedonic
      behavior. Prior to terminal perfusion, the animals were injected with
      bromodeoxyuridine, a marker of proliferating cells. The number of proliferating
      cells and total cell number and volume were estimated for the granule cell layer
      of the ventral hippocampal formation. Unlike CMS, chronic injections with MAM did
      not induce anhedonia-like symptoms in rats. Both MAM-treated and CMS-exposed
      groups of rats showed a comparable significant reduction in cell proliferation in
      the granular cell layer of the ventral hippocampal formation. However, the total
      cell number was reduced for CMS-exposed rats only while the granule cell layer
      volume was conserved for both groups. Our results show that suppression of cell
      proliferation in the hippocampal formation is not an absolute factor for
      induction of an anhedonia-like state in rats. However, it may still represent an
      important causal factor for vulnerable subjects.

PMID- 19595675
TI  - Trigeminal projections on gustatory neurons of the nucleus of the solitary tract:
      a double-label strategy using electrical stimulation of the chorda tympani and
      tracer injection in the lingual nerve.
AB  - Taste and sensory information are closely associated and our electrophysiological
      studies showed a trigeminal modulation of gustatory neurons in the nucleus of the
      solitary tract (NST). Chorda tympani (CT) and lingual nerves (LN) converge
      centrally in the rostral subdivision of the NST in hamsters and rats. However, no
      study has yet revealed the details of this overlap on a same section. We
      therefore used a double-label strategy to visualize neurons in the NST that
      receive both trigeminal and gustatory inputs. An anterograde tracer (BDA,
      Biotinylated Dextran Amine) was applied unilaterally to the cut central end of
      the LN in male Sprague-Dawley rats. One week later, the ipsilateral CT was
      electrically stimulated, after which animals were perfused and brainstem sections
      double-labelled for Fos immunoreactivity of activated NST neurons and BDA
      labelling of LN afferents. Our results permitted to circumscribe the regional
      overlap of the trigeminal and CT afferents mainly in the rostral central (RC)
      subdivision of the gustatory NST. Fos-immunoreactive neurons were observed to be
      closely apposed by BDA-labelled fibres and terminal boutons. Such varicosities
      mainly "en passant" were especially present in the RC zone of the nucleus. These
      observations provide an anatomical substrate for trigemino-gustatory
      interactions.

PMID- 19595677
TI  - Glioma-induced remodeling of the neurovascular unit.
AB  - The normal BBB (blood-brain barrier) consists of a series of structures
      collectively known as neurovascular units, or NVU, that are composed of
      endothelial cells and astrocyte endfeet separated by a basal lamina at their
      interface. The integrity of the BBB and specifically endothelial tight junctions
      is maintained by interactions between these different components and the local
      microenvironment of the NVU. Central nervous system cancers such as gliomas
      disrupt the integrity of the BBB and this compromise is associated with increased
      tumor growth and invasion of the surrounding brain parenchyma. Because the
      relationship between glioma-induced BBB breakdown and glioma invasion remains
      poorly understood, and the host microenvironment can influence tumor cell
      migration, we used immunohistochemical techniques to characterize tumor
      associated BBB remodeling. Using an orthotopic xenograft model of glioma, we
      demonstrate that tumor cells induce specific changes in the composition of the
      basal lamina and in astrocytic components of the NVU. We suggest that these
      changes may be essential to understand the capacity of gliomas to regulate BBB
      integrity and as such, glioma invasion into brain parenchyma.

PMID- 19595676
TI  - Cellular mechanisms underlying affective resiliency: the role of glucocorticoid
      receptor- and mitochondrially-mediated plasticity.
AB  - Bipolar disorder (BPD) is a devastating psychiatric illness marked by recurrent
      episodes of mania and depression. While the underlying pathophysiology of BPD
      remains elusive, an abnormal hypothalamic-pituitary-adrenal (HPA) axis and
      dysfunctional glucocorticoid receptor (GR) signaling are considered hallmarks.
      This review will examine how targeting resiliency signaling cascades at the
      cellular level may serve as a mechanism to treat BPD. Here, cellular resiliency
      is defined as the ability of a cell to adapt to an insult or stressor. Such
      resiliency at the cellular level could confer resiliency at the systems level
      and, ultimately, help individuals to cope with stressors or recover from
      depressive or manic states. This review will focus on four molecular targets of
      mood stabilizers that are known to play integral roles in these cellular
      resiliency signaling pathways: (1) B-cell CLL/lymphoma 2 (Bcl-2), (2) Bcl-2
      associated athanogene (BAG-1), (3) glucocorticoid receptors (GRs), and (4) 51 kDa
      FK506-binding protein (FKBP5). These targets have emerged from neurobiological
      and human genetic studies and employ mechanisms that modulate GR function or
      promote anti-apoptotic processes critical to affective resilience. Future
      research should focus on elucidating sustainable treatments that target
      resiliency factors-such as BAG-1 or FKBP5-which could ultimately be used to treat
      individuals suffering from BPD and prevent relapses in afflicted individuals.
      Further identification of resiliency and susceptibility factors will also be
      vital. Ultimately, these developments would allow for the treatment of
      susceptible individuals prior to the development of BPD.

PMID- 19595678
TI  - Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances
      ischemia-like neurodegeneration.
AB  - Microglial cells have been attributed both neuroprotective and neurodegenerative
      roles in cerebral ischemia. This study presents an immunotoxic method for
      depletion of microglia from mouse hippocampal slice cultures and the effect of
      this on ischemia-like oxygen-glucose deprivation (OGD). For microglial depletion
      hippocampal slice cultures were exposed for 7 days to saporin coupled to an
      antibody against the microglial receptor Mac1 (Mac1-sap). When subjected to OGD
      immediately thereafter, resulting neurodegeneration was quantified as cellular
      uptake of propidium iodide (PI). Cultures were processed 1, 7 or 14 days after
      OGD for general cell staining and immunohistochemistry for neuronal, astroglial
      and microglial markers. Following Mac1-sap treatment there was a near total loss
      of microglia, these microglia-depleted cultures displayed a significant increase
      in PI uptake and astrogliosis 1 day after OGD compared to non-depleted cultures.
      In cultures surviving 7 and 14 days after OGD there was a decrease in PI uptake
      compared to 1 day after OGD. At 7 and 14 days after OGD the differences in Mac1
      sap treated or non-treated cultures were still noticeable in terms of more neuron
      loss in cultures deprived of microglia, while the astroglial reactivity seemed to
      equalize. Based on the finding that depletion of microglia significantly
      increased OGD-induced CA1 pyramidal cell degeneration, we conclude that microglia
      at least in the initial phase of injury exert a neuroprotective role in mouse
      hippocampal slice cultures.

PMID- 19595679
TI  - Detecting directional influence in fMRI connectivity analysis using PCA based
      Granger causality.
AB  - An fMRI connectivity analysis approach combining both principal component
      analysis (PCA) and Granger causality method (GCM) is proposed to study
      directional influence between functional brain regions. Both simulated data and
      human fMRI data obtained during behavioral tasks were used to validate this
      method. If PCA is first used to reduce number of fMRI time series, then more
      energy and information features in the signal can be preserved than using
      averaged values from brain regions of interest. Subsequently, GCM can be applied
      to principal components extracted in order to further investigate effective
      connectivity. The simulation demonstrated that by using GCM with PCA, between
      region causalities were better represented than using GCM with average values.
      Furthermore, after localizing an emotion task-induced activation in the anterior
      cingulate cortex, inferior frontal sulcus and amygdala, the directional
      influences among these brain regions were resolved using our new approach. These
      results indicate that using PCA may improve upon application of existing GCMs in
      study of human brain effective connectivity.

PMID- 19595680
TI  - Characterisation of the timing of binding of the hypoxia tracer FMISO after
      stroke.
AB  - The hypoxia tracer fluorine-18 fluoromisonidazole ([18F]FMISO) and its tritiated
      counterpart ([(3)H]FMISO) have been used as markers of potentially salvageable
      brain (ischemic penumbra) after stroke. In experimental models, the dynamics and
      half-life of [3H]FMISO allow concurrent histology after 24 h. Our aim was to
      further validate these techniques, by determining the optimum tracer exposure
      interval to delineate ischemic penumbra, and the effects of prolonged exposure on
      tracer retention in permanent ischemia. Middle cerebral artery occlusion (MCAO)
      of varying durations was created in rats using the thread occlusion model.
      Autoradiography using objective thresholding to define tracer-retention volume
      was performed to determine the time course of tracer retention in hypoxic tissues
      and the duration of ongoing retention after bolus administration. An ischemic
      duration of < or =90 min resulted in a tracer-retention volume underestimating
      'tissue at risk' (histological infarction 24 h after permanent occlusion) by
      >1/2. Two hour ischemia resulted in a volume equal to 'tissue at risk'. Twenty
      four hour permanent ischemia resulted in tracer-retaining tissue volumes greater
      than final infarction. However, the use of more stringent thresholding of
      autoradiographic signal produced a volume of FMISO retention closely
      approximating infarct volume. The findings indicate that the timing of imaging is
      crucial, with an optimal imaging time of 2 h using the current threshold. Earlier
      imaging is limited by tracer dynamics with this particular agent, however
      autoradiography with a longer ischemic interval (permanent occlusion) is feasible
      with modified thresholds. These findings support a role for hypoxia tracers in
      providing new insight into the ischemic penumbra.

PMID- 19595682
TI  - Combined effects of quercetin and alpha-tocopherol on lipids and glycoprotein
      components in isoproterenol induced myocardial infarcted Wistar rats.
AB  - This study was aimed to evaluate the combined effects of quercetin and alpha
      tocopherol on lipid metabolism and glycoprotein components in isoproterenol
      induced myocardial infarction in Wistar rats. Myocardial infarction in rats was
      induced by isoproterenol (100mg/kg) at an interval of 24h for 2 days. Quercetin
      (10 mg/kg) and alpha-tocopherol (10 mg/kg) were given to rats as pretreatment for
      14 days orally using an intragastric tube. Quercetin and alpha-tocopherol
      significantly reduced the levels of cholesterol, triglycerides and free fatty
      acids in the serum and heart and serum phospholipids and significantly increased
      the levels of heart phospholipids in isoproterenol induced rats. They also
      significantly decreased the activity of plasma and liver 3-hydroxy-3
      methylglutaryl-coenzyme-A reductase and increased the activity of plasma and
      liver lecithin cholesterol acyl transferase in isoproterenol treated rats. In
      addition to this, they also significantly reduced the levels of hexose,
      hexosamine, fucose and sialic acid in the serum and heart of isoproterenol
      treated rats. Quercetin and alpha-tocopherol also showed significant decrease in
      plasma lipid peroxidation products (thiobarbituric acid reactive substances and
      lipid hydroperoxides). Pretreatment with quercetin alone and alpha-tocopherol
      alone showed significant effect in all the biochemical parameters in myocardial
      infarcted rats. But, combined pretreatment with quercetin and alpha-tocopherol
      normalized all the above mentioned biochemical parameters in isoproterenol
      treated myocardial infarction in rats. Thus, the experiment clearly showed that
      quercetin and alpha-tocopherol prevented the accumulation of lipids and
      glycoprotein components in myocardial infarcted rats by their anti-lipid
      peroxidative effect. This study also showed that combined pretreatment was better
      than single pretreatment.

PMID- 19595683
TI  - Mass spectrometric identification of human phosphate cytidylyltransferase 1 as a
      novel calcium oxalate crystal growth inhibitor purified from human renal stone
      matrix.
AB  - BACKGROUND: A relatively small number of well-characterized inhibitors of kidney
      stone formation have been identified from the previous research involved in its
      formation. In this study conventional biochemical methods have been combined with
      recent advances in mass spectrometry (MS) to identify a novel calcium oxalate
      (CaOx) crystal growth inhibitor in human renal stone matrix. METHODS: Proteins
      were isolated from the matrix of human CaOx containing kidney stones. Proteins
      having MW>10 kDa were subjected to anion exchange and molecular-sieve
      chromatography. Protein fractions were tested for their effects on CaOx crystal
      growth. Most potent fraction P2' was excised, in-gel tryptic digested and
      identified by matrix assisted laser desorption/ionization-time of flight (MALDI
      TOF) MS. RESULTS: An anionic protein (MW approximately 42 kDa) with potent
      inhibitory activity against CaOx crystal growth was purified. Its homogeneity was
      confirmed by RP-HPLC. It was identified by MALDI-TOF-MS followed by database
      search on MASCOT server as human phosphate cytidylyltransferase 1, beta.
      Molecular weight of this novel CaOx crystal growth inhibitor from human renal
      stone matrix is also the same as that of human phosphate cytidylyltransferase 1,
      choline, beta. CONCLUSIONS: Human phosphate cytidylyltransferase 1, choline, beta
      is a novel CaOx crystal growth inhibitor. It is involved in the biosynthesis of
      phosphatidylcholine which happens to be an important constituent of human renal
      stones and is also reported to have an antilithiatic effect.

PMID- 19595681
TI  - A combined effect of dextromethorphan and melatonin on neuropathic pain behavior
      in rats.
AB  - Previous study has shown that administration of melatonin into the anterior
      cingulate cortex contralateral to peripheral nerve injury prevented exacerbation
      of mechanical allodynia with a concurrent improvement of depression-like behavior
      in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present
      study, we examined the effect of the individual versus combined treatment of
      melatonin and/or dextromethorphan (DM), a clinically available N-methyl-d
      aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic
      constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and
      mechanical allodynia) were established at one week after CCI. WKY rats were then
      treated intraperitoneally with various doses of melatonin, DM or their
      combination once daily for the following week. At the end of this one-week
      treatment, behavioral tests were repeated in these same rats. While DM alone was
      effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60
      mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By
      comparison, administration of melatonin alone was effective in reducing thermal
      hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested
      in this experiment. Melatonin alone failed to reverse allodynia at all three
      tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal
      administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed
      both thermal hyperalgesia and mechanical allodynia although each individual dose
      alone did not reduce pain behaviors. These results suggest that a combination of
      melatonin with a clinically available NMDA receptor antagonist might be more
      effective than either drug alone for the treatment of neuropathic pain.

PMID- 19595684
TI  - Detection of the JAK2 V617F missense mutation by high resolution melting analysis
      and its validation.
AB  - BACKGROUND: Janus kinase 2 (JAK2) is a tyrosine kinase involved in the cytokine
      signaling of several growth factors such as erythropoietin and thrombopoietin in
      normal and neoplastic cells. The G to T exchange at nucleotide 1849 in exon 14 of
      the JAK2 gene leads to a substitution of valine with phenylalanine at the amino
      acid position 617 (V617F) of the JAK2 protein. Currently, the occurrence of the
      JAK2 V617F mutation is well recognized in chronic myeloproliferative disorders
      (MPDs). METHODS: We identified JAK2 V617F missense mutation in patients with MPD
      by high resolution melting (HRM) analysis. HRM analysis is a new gene scan tool
      that quickly performs the PCR and identifies sequences alterations without
      requiring post-PCR treatment. This study included 7 PV patients (41.1%), 6 ET
      patients (35.3%), and 4 myelofibrosis patients (23.5%). Additionally, our
      methodology was compared with amplification refractory mutation system (ARMS)
      assay. RESULTS: Up to 5% of the JAK2 V617F mutation was successfully detected in
      patients with MPD using HRM analysis. Eleven out of 17 patients (64.7%) were
      positive for the presence of JAK2 V617F mutation. The prevalence of mutation in
      the different subtypes of MPDs was 85.7% in PV (6 of 7 patients), 66.7% in ET (4
      of 6) and 5.9% in myelofibrosis (1 of 4). The results proved 100% comparable to
      those obtained by ARMS assay. CONCLUSIONS: The HRM analysis is a rapid and
      effective technique for the detection of JAK2 V617F missense mutation.

PMID- 19595685
TI  - The intravenous anesthetics barbiturates inhibit hypoxia-inducible factor 1
      activation.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor of hypoxia
      induced gene expression. Anesthetics and perioperative drugs have been reported
      to affect HIF-1 activity. However, the effect of barbiturates on HIF-1 activity
      has not been reported. In this study, we investigated the effect of thiopental
      and thiamylal on HIF-1 activity using the neuronal SH-SY5Y cells, the non
      neuronal HEK293 cells, and the macrophage-differentiated THP-1 cells. Cells were
      exposed to 20% or 1% O(2) conditions with or without thiopental or thiamylal
      treatment. The cell lysate were subjected to Western blot analysis using anti-HIF
      1alpha and -HIF-1beta antibodies. HIF-1-dependent gene expression was
      investigated by semi-quantitative real-time RT-PCR and luciferase assay.
      Hydroxylation of HIF-1alpha protein was evaluated by in vitro pulldown assay
      using recombinant protein. Both thiopental and thiamylal reversibly suppressed
      hypoxia-induced HIF-1 activation in the neuronal and the non-neuronal cells in a
      dose-dependent manner. Moreover, the barbiturates inhibited lipopolysaccharide
      induced HIF-1alpha expression in THP-1 cells. The HIF-1-downstream gene
      expression was also inhibited by the barbiturates. HIFalpha-hydroxylases activity
      and HIF-1alpha stability were not affected but the HIF-1alpha protein
      neosynthesis was inhibited by the barbiturates. Our experimental results indicate
      that barbiturates inhibit induced HIF-1 activation and downstream genes
      expression.

PMID- 19595687
TI  - The interaction of sildenafil with the anticonvulsant effect of diazepam.
AB  - In order to assess the role of nitric oxide/cyclicGMP signaling pathway in the
      anticonvulsant effect of benzodiazepines, we studied the potential interaction of
      a phosphodiesterase type 5 inhibitor, sildenafil with the effect of diazepam on a
      mouse model of clonic seizures induced by intravenous infusion of GABA
      antagonist, pentylenetetrazole (PTZ). Administration of sildenafil (10 mg/kg; per
      se effective on seizure threshold) could abolish the anticonvulsive effect of
      diazepam, and a subeffective dose (5 mg/kg), when added to NO precursor L
      arginine (50 mg/kg) could cause the same effect. Conversely, subeffective doses
      of diazepam (0.02 mg/kg) and NO synthase inhibitor N(omega)-nitro-L-arginine
      methyl ester (L-NAME, 5 mg/kg), administered together, reversed the proconvulsive
      effect of sildenafil. Our findings indicate that the enhancement of NO/cGMP
      signaling pathway by sildenafil attenuates the anticonvulsant effect of the
      benzodiazepine prototype, diazepam. This suggests that the effects of
      facilitating GABA(A)-mediated inhibition and modulating NO pathways are additive
      and there might be a role for NO pathway in benzodiazepine effect against PTZ
      induced seizures in mice.

PMID- 19595688
TI  - Changes in the plasma levels of insulin-like growth factor-I from the onset of
      spawning migration through upstream migration in chum salmon.
AB  - An increase in activity of the pituitary-gonadal axis (PG-axis) and gonadal
      development are essential for the onset of spawning migration of chum salmon from
      the Bering Sea. In the Bering Sea, fish with larger body sizes initiated gonadal
      development and commenced spawning migration to the natal river by the end of
      summer. We thus hypothesized that insulin-like growth factor-I (IGF-I), a
      somatotropic signal that interacts with the PG-axis, can be one of such factors
      responsible for the onset of migration, and examined changes in plasma levels and
      hepatic expression of IGF-I gene in oceanic and homing chum salmon in 2001-2003.
      The plasma IGF-I levels and corresponding body sizes in maturing adults, which
      had developing gonads, were significantly higher than those in immature fish in
      all years examined. Such increase in the plasma IGF-I levels in maturing fish was
      observed even in the Gulf of Alaska during February 2006, while coincident
      increase was not observed in the hepatic amounts of IGF-I mRNA. In autumn, the
      plasma IGF-I levels in homing adults decreased during upstream migration in the
      Ishikari River-Ishikari bay water system in Hokkaido, Japan. In conclusion, the
      plasma IGF-I levels increased with gonadal development when chum salmon migrated
      from the winter Gulf of Alaska to the summer Bering Sea. Circulating IGF-I may
      interact with the PG-axis and promote gonadal development that is inseparable
      from the onset of spawning migration. Circulating IGF-I levels were thereafter
      lowered in accordance with final maturation during upstream migration in the
      breeding season.

PMID- 19595686
TI  - A comparison of glycemic control, water retention, and musculoskeletal effects of
      balaglitazone and pioglitazone in diet-induced obese rats.
AB  - Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which
      work as insulin sensitizers, are approved for type 2 diabetes. However, adverse
      effects, such as oedemas, infarctions, and increased fracture rates, limit their
      applicability. We performed a head-to-head comparison of equipotent glucose
      lowering concentrations of the partial PPARgamma agonist balaglitazone and the
      full agonist pioglitazone in male diet-induced obese rats, to investigate effects
      on bone formation, fluid retention and fat accumulation. Sixty male dio induced
      obese rats were divided into five categories: vehicle, pioglitazone 10 mg/kg,
      pioglitazone 30 mg/kg, balaglitazone 5 mg/kg, balaglitazone 10 mg/kg. At day -7,
      21 and 42 fasting serum samples were collected and whole body tissue composition
      was evaluated by MR scanning. Food intake and bodyweights were monitored during
      the study period. At day 42, an oral glucose tolerance test was performed to
      evaluate glucose homeostasis in the rats. During oral glucose tolerance test both
      pioglitazone and balaglitazone lowered baseline glucose and maintained the
      suppression during the oral glucose tolerance test. Both lowered basal insulin,
      peak insulin secretion and total insulin during oral glucose tolerance test. Both
      drugs increased bodyweight, although this was more pronounced in the pioglitazone
      30 group. MR scans of body fat and water showed that all treatment groups
      increased their fat mass, whereas only the pioglitazone 30 group accumulated
      water. Pioglitazone treatment led to reduction of the bone formation marker
      osteocalcin, whereas balaglitazone treatment did not affect it. Balaglitazone is
      a novel PPARgamma agonist, which potently lowers glucose levels, while it neither
      affects fluid retention nor bone formation parameters.

PMID- 19595689
TI  - Cxcl12a-Cxcr4b signaling is important for proper development of the forebrain
      GnRH system in zebrafish.
AB  - Hypothalamic gonadotropin-releasing hormone (GnRH) neurons control pituitary
      gonadotropin secretion and gametogenesis. In the course of development, these
      neurons migrate from the olfactory placode to the hypothalamus. The precise
      molecular mechanism of this neuronal migration is unclear. Here, we investigated
      whether the chemokine receptor, Cxcr4b, and its cognate ligand, Cxcl12a, are
      required for proper migration of GnRH3 neurons in zebrafish. Deviated GnRH3
      axonal projections and neuronal migration were detected in larvae that carry a
      homozygote cxcr4b mutation. Similarly, knockdown of Cxcr4b or Cxcl12a led to the
      appearance of abnormal GnRH3 axonal projections and cell migration, including
      absence of the characteristic lateral crossing of GnRH3 axons at the anterior
      commissure and optic chiasm. Double-labeling analysis has shown that cxcr4b and
      cxcl12a are expressed along the GnRH3 migration pathway (i.e. olfactory placode,
      terminal nerve and the optic chiasm). The results of this study suggest that the
      Cxcl12a-Cxcr4b ligand-receptor pair are involved in the migration of GnRH3
      neurons in zebrafish, and are therefore crucial for the development of this
      system.

PMID- 19595691
TI  - Development of the adrenal stress response in the Florida scrub-jay (Aphelocoma
      coerulescens).
AB  - Nestlings of altricial species undergo a period of substantial growth and
      development in the nest after hatching. The hypothalamic-pituitary-adrenal axis
      regulates the release of stress hormones such as corticosterone, which in adults
      is critical in allowing an animal to respond to a stressor. However, activation
      of this axis in young birds may be detrimental to growth and possibly survival.
      The developmental hypothesis predicts that altricial nestlings should display a
      dampened corticosterone response to stress as a means of protection against the
      potentially harmful effects of elevated corticosterone. We examined this
      hypothesis in Florida scrub-jays, a cooperatively breeding species with altricial
      young. Blood samples were collected from nestlings, nutritionally independent
      young, and yearlings for measurement of corticosterone levels. Baseline
      corticosterone levels did not differ between age-classes; however, stress-induced
      corticosterone levels were highest in yearlings, intermediate in independent
      young, and lowest in nestlings. The nestling stress response was also of a
      shorter duration than the response in independent young and yearlings. This
      variation in stress responsiveness across ages may be an adaptive mechanism to
      protect the developing bird from the negative effects of corticosterone on growth
      and cognitive development.

PMID- 19595690
TI  - Suppressed production of methyl farnesoid hormones yields developmental defects
      and lethality in Drosophila larvae.
AB  - A long-unresolved question in the developmental biology of Drosophila
      melanogaster has been whether methyl farnesoid hormones secreted by the ring
      gland are necessary for larval maturation and metamorphosis. In this study, we
      have used RNAi techniques to inhibit 3-Hydroxy-3-Methylglutaryl CoA Reductase
      (HMGCR) expression selectively in the corpora allatal cells that produce the
      circulating farnesoid hormones. The developing larvae manifest a number of
      developmental, metabolic and morphogenetic derangements. These defects included
      the exhibition of an "ultraspiracle" death phenotype at the 1st to 2nd instar
      larval molt, similar to that exhibited by animals that are null for the farnesoid
      receptor ultraspiracle. The few larvae surviving past a second lethal period at
      the 2nd to 3rd instar larval molt, again with "ultraspiracle" phenotype, often
      became developmentally arrested after either attaining a misformed puparium or
      after formation of the white pupa. Survival past the "ultraspiracle" lethal
      phenotype could be rescued by dietary provision of an endogenous dedicated
      precursor to the three naturally secreted methyl farnesoid hormones. In addition
      to these developmental and morphogenetic defects, most larvae that survived to
      the late second instar exhibited a posterior-originating melanization of the
      tracheal system. These results support the hypothesis that larval methyl
      farnesoid hormones are necessary for larval survival and morphogenetic
      transformation through the larval and pupal metamorphic processes.

PMID- 19595692
TI  - The onset of cortisol synthesis and the stress response is independent of changes
      in CYP11B or CYP21 mRNA levels in larval red drum (Sciaenops ocellatus).
AB  - Although cortisol plays an important role in teleost development, the onset of
      cortisol production and the cortisol stress response in teleosts remain poorly
      understood. Here we have reported basal cortisol levels and the development of
      the cortisol stress response in larval red drum (Sciaenops ocellatus). We
      isolated partial nucleic acid sequences encoding two key corticosteroidogenic
      enzymes, CYP11B and CYP21 and assessed ontogenetic patterns of their mRNA levels
      relative to basal and stress-induced cortisol production. Basal cortisol was
      first detected 3 days post-hatch (DPH) and reached a maximum at 9 DPH. Cortisol
      did not increase in response to an acute stressor prior to 6 DPH. From 6 DPH
      forward, stress caused significant increases in larval cortisol content. Stress
      induced cortisol levels in 6-9 DPH larvae were highest 1h post-stress. In larvae
      11 DPH and older, the highest cortisol measurements occurred 0.5h post-stress.
      Elevated cortisol was still evident after 3h in 6 DPH larvae. From 11 DPH onward,
      basal cortisol levels were reestablished in larvae by 1h post-stress. CYP11B and
      CYP21 transcripts were detected in red drum 12h prior to hatching and in all post
      hatch larvae examined. Changes in CYP11B and CYP21 mRNA levels did not occur in
      association with the ontogenetic appearance of cortisol, or the onset of the
      stress response. As larvae developed, the dynamics of the cortisol stress
      response matured from a low magnitude, slow recovery response, to a response
      similar to that observed in juvenile and adult fish.

PMID- 19595693
TI  - Edema and fluid dynamics in connective tissue remodelling.
AB  - The review describes the role of loose connective tissues with focus on
      transcapillary exchange and edema formation with relevance for inflammation,
      fibrosis and tumors. Based on studies in these tissues, comparisons are made to
      the fibrotic processes in the heart.

PMID- 19595694
TI  - Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis.
AB  - In diabetes mellitus, alterations in cardiac structure/function in the absence of
      ischemic heart disease, hypertension or other cardiac pathologies are termed
      diabetic cardiomyopathy. In the United States, the prevalence of diabetes
      mellitus continues to rise and the disease currently affects about 8% of the
      general population. Hence, the use of appropriate diagnostic strategies for
      diabetic cardiomyopathy, which may help correctly identify the disease at early
      stages and implement suitable corrective therapies is imperative. Currently,
      there is no single diagnostic method for the identification of diabetic
      cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac
      structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition.
      Early changes in cardiac function are typically manifested as abnormal diastolic
      function that with time leads to loss of contractile function. Echocardiography
      based methods currently stand as the preferred diagnostic approach for diabetic
      cardiomyopathy, due to its wide availability and economical use. In addition to
      conventional techniques, magnetic resonance imaging and spectroscopy along with
      contrast agents are now leading new approaches in the diagnosis of myocardial
      fibrosis, and cardiac and hepatic metabolic changes. These strategies can be
      complemented with serum biomarkers so they can offer a clear picture as to
      diabetes-induced changes in cardiac structure/function even at very early stages
      of the disease. This review article intends to provide a summary of experimental
      and routine tools currently available to diagnose diabetic cardiomyopathy induced
      changes in cardiac structure/function. These tools can be reliably used in either
      experimental models of diabetes or for clinical applications.

PMID- 19595696
TI  - Knockdown of microRNA-181 by lentivirus mediated siRNA expression vector
      decreases the arrhythmogenic effect of skeletal myoblast transplantation in rat
      with myocardial infarction.
AB  - The arrhythmogenic effect of intracardiac skeletal myoblast (SKM) transplantation
      may be related to the differentiation state of SKMs. We tested the hypothesis
      that lentivirus mediated siRNA against the loop region of miRNA-181a could
      upregulate the SKMs differentiation repressor homeobox protein A11 (Hox-A11) and
      reduce the arrhythmias post SKM transplantation into ischemic myocardium of rats.
      Primary cultured SKMs were transfected with Lenti-siR-miR-181 (recombined
      lentivirus expressing the unique siRNA against miR-181a, LV group). Real-time PCR
      showed that miRNA-181a level was significantly decreased and Hox-A11 protein
      level significantly increased in LV group than in control group at days 5 and
      days 7 post Lentivirus transfection. Knockdown of miRNA-181a significantly
      promoted SKMs' growth and attenuated the connexin43 downregulation in SKMs in
      vitro. Seven days after left coronary artery ligation, rats were randomized to
      receive intramyocardial injection of either 5x10(6) SKMs transfected with Lenti
      siR-miR-181 (MI-SKMLV), 5x10(6) Lenti-siLUC SKMs (MI-SKM) or PBS (MI-PBS).
      Systolic function was significantly improved in both MI-SKM and MI-SKMLV groups
      fourteen days after injection. Incidence of inducible self-terminating
      ventricular tachycardia was significantly lower in MI-SKMLV than that in MI-SKM
      group. Engraftments of SKMs with knockdowned miRNA-181a similarly improved
      cardiac function as SKM transplantation but significantly decreased the
      arrhythmogenic effect of SKM transplantation in rats with experimental myocardial
      infarction.

PMID- 19595697
TI  - Dehydroepiandrosterone sulfate linked to physiologic response against hot spring
      immersion.
AB  - The steroid dehydroepiandrosterone sulfate (DHEA-S) is associated with longevity
      and adaptation against external stress in humans. The aim of the study was to
      investigate the acute effect of a 30-min hot spring immersion at 41 degrees C on
      insulin resistance measures of 16 male subjects, in relation to DHEA-S level. To
      elucidate the role of DHEA-S in the coping against the heat stress, all subjects
      were evenly divided into lower and upper halves according to their baseline DHEA
      S concentrations. The levels of glucose, insulin, blood pressure, and stress
      hormones (growth hormone, testosterone, and cortisol) in both groups were
      compared before and after hot spring immersion. The result shows that hot spring
      immersion significantly increased heart rate and reduced diastolic blood
      pressure, both of which were paralleled with a drop of DHEA-S concentration.
      Homeostasis model assessment for insulin resistance (HOMA-IR) and area under
      curve of glucose (GAUC) of oral glucose tolerance test were significantly
      increased by the hot spring immersion only in the Low DHEA-S group. Likewise, hot
      spring immersion caused an opposing effect on cortisol changes for the Low and
      High DHEA-S groups (+95% vs. -33%, p<0.05), respectively. In conclusion, hot
      spring bathing induced insulin resistance confined only to those Low DHEA-S
      individuals. This response may be associated with a stress response such as
      increased cortisol levels.

PMID- 19595695
TI  - High-fat feeding in cardiomyocyte-restricted PPARdelta knockout mice leads to
      cardiac overexpression of lipid metabolic genes but fails to rescue cardiac
      phenotypes.
AB  - Peroxisome proliferator-activated receptor delta (PPARdelta) is an essential
      determinant of basal myocardial fatty acid oxidation (FAO) and bioenergetics. We
      wished to determine whether increased lipid loading affects the PPARdelta
      deficient heart in transcriptional regulation of FAO and in the development of
      cardiac pathology. Cardiomyocyte-restricted PPARdelta knockout (CR-PPARdelta(-/
      )) and control (alpha-MyHC-Cre) mice were subjected to 48 h of fasting and to a
      long-term maintenance on a (28 weeks) high-fat diet (HFD). The expression of key
      FAO proteins in heart was examined. Serum lipid profiles, cardiac pathology, and
      changes of various transduction signaling pathways were also examined. Mice
      subjected to fasting exhibited upregulated transcript expression of FAO genes in
      the CR-PPARdelta(-/-) hearts. Moreover, long-term HFD in CR-PPARdelta(-/-) mice
      induced a strikingly greater transcriptional response. After HFD, genes encoding
      key FAO enzymes were expressed remarkably more in CR-PPARdelta(-/-) hearts than
      in those of control mice. Despite the marked rise of FAO gene expression,
      corresponding protein expression remained low in the CR-PPARdelta(-/-) heart,
      accompanied by abnormalities in sarcomere structures and mitochondria that were
      similar to those of CR-PPARdelta(-/-) hearts with regular chow feeding. The CR
      PPARdelta(-/-) mice displayed increased expression of PPARgamma co-activator
      1alpha (PGC-1alpha) and PPARalpha in the heart with deactivated Akt and p42/44
      MAPK signaling in response to HFD. We conclude that PPARdelta is an essential
      determinant of myocardial FAO. Increased lipid intake activates cardiac
      expression of FAO genes via PPARalpha/PGC-1alpha pathway, albeit it is not
      sufficient to improve cardiac pathology due to PPARdelta deficiency.

PMID- 19595698
TI  - Ypsilandrosides C-G, five new spirostanol saponins from Ypsilandra thibetica.
AB  - A further phytochemical investigation on the whole plants of Ypsilandra thibetica
      yielded one sapogenin and 12 spirostanol saponins. Five of these are new
      compounds, designated as ypsilandrosides C-G (2-6). Their structures were
      determined by detailed spectroscopic analysis, including extensive 1D and 2D NMR
      data, and by the result of a hydrolytic reaction. Compounds 2-5 were rare
      steroidal saponins that an apiofuranosyl unit was directly linked at C-3 of the
      aglycone. Selected spirostanol saponins (2-6, 9) were tested for their cytotoxic
      activities against K562, SPC-A-1, BGC-823, Eca-109, and AGS cell lines. Compounds
      6 and 9 showed moderate inhibitory activity against all five cell lines. The
      antifungal properties of the new spirostanol saponins (2-6) against Candida
      albicans were also determined.

PMID- 19595699
TI  - Combinational chelation therapy abrogates lead-induced neurodegeneration in rats.
AB  - Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads
      to numerous neurobehavioral and physiological alterations. The ability of lead to
      bind sulfhydryl groups or compete with calcium could be one of the reasons for
      its debilitating effects. In the present study, we addressed: i) if chelation
      therapy could circumvent the altered oxidative stress and prevent neuronal
      apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could
      reverse biochemical and behavioral changes, and iii) if mono or combinational
      therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA)
      is more effective than individual thiol chelator in lead-exposed rats. Results
      indicated that lead caused a significant increase in reactive oxygen species,
      nitric oxide, and intracellular free calcium levels along with altered behavioral
      abnormalities in locomotor activity, exploratory behavior, learning, and memory
      that were supported by changes in neurotransmitter levels. A fall in membrane
      potential, release of cytochrome c, and DNA damage indicated mitochondrial
      dependent apoptosis. Most of these alterations showed significant recovery
      following combined therapy with captopril with MiADMSA and to a smaller extend
      with captopril+DMSA over monotherapy with these chelators. It could be concluded
      from our present results that co-administration of a potent antioxidant (like
      captopril) might be a better treatment protocol than monotherapy to counter lead
      induced oxidative stress. The major highlight of the work is an interesting
      experimental evidence of the efficacy of combinational therapy using an
      antioxidant with a thiol chelator in reversing neurological dystrophy caused due
      to chronic lead exposure in rats.

PMID- 19595700
TI  - Bromocriptine induces parapoptosis as the main type of cell death responsible for
      experimental pituitary tumor shrinkage.
AB  - Bromocriptine (Bc) produces pituitary tumoral mass regression which induces the
      cellular death that was classically described as apoptosis. However, recent works
      have related that other mechanisms of cell death could also be involved in the
      maintenance of physiological and pathological pituitary homeostasis. The aim of
      this study was to evaluate and characterize the different types of cell death in
      the involution induced by Bc in experimental rat pituitary tumors. The current
      study demonstrated that Bc induced an effective regression of estrogen induced
      pituitary tumors by a mechanism identified as parapoptosis. This alternative cell
      death was ultrastructurally recognized by extensive cytoplasmic vacuolization and
      an increased cell electron density, represented around 25% of the total pituitary
      cells counted. Furthermore, the results obtained from biochemical assays did not
      correspond to the criteria of apoptosis or necrosis. We also investigated the
      participation of p38, ERK1/2 and PKC delta in the parapoptotic pathway. An
      important observation was the significant increase in phosphorylated forms of
      these MAPKs, the holoenzyme and catalytic fragments of PKC delta in nuclear
      fractions after Bc administration compared to control and estrogen treated rats.
      Furthermore, the immunolocalization at ultrastructural level of these kinases
      showed a similar distribution pattern, with a prevalent localization at nuclear
      level in lactotrophs from Bc treated rats. In summary, we determined that
      parapoptosis is the predominant cell death type involved in the regression of
      pituitary tumors in response to Bc treatment, and may cause the activation of PKC
      delta, ERK1/2 and p38.

PMID- 19595701
TI  - Effects of Madagascar yam extracts, Dioscorea antaly, on embryo-larval
      development of medaka fish, Oryzias latipes.
AB  - The yams edible starchy tubers, are of cultural, economic and nutritional
      importance in tropical and subtropical regions. The present study concerns the
      analysis at different levels of Dioscorea antaly toxicity to medaka embryo-larval
      development. The incubation of medaka fish embryos in a medium containing
      Dioscorea antaly extract resulted in a dose dependent reduction in survival rate.
      Survival rates were reduced up to 100% with extract concentrations of 4mg mL(-1).
      The LD(50) was estimated to be 0.86mg mL(-1)Dioscorea antaly. Anatomopathological
      studies did not show any caustic effects, irritation to mouth, throat or
      intestinal tract in surviving embryos but rather an inflammatory reaction in the
      liver. The data presented in this paper thus extends the use of medaka embryos as
      a valuable model to analyze the effects of food toxins.

PMID- 19595702
TI  - "Live, Learn and Play": building strategic alliances between professional sports
      and public health.
AB  - Public-private partnerships allow communities and corporate entities to pool
      resources to address a mission of relevance to their common constituency or
      consumer base. Collaborations between public health and professional sports may
      present unique opportunities to improve health outcomes related to physical
      activity since athletes are fitness icons, both for adults and children. There
      are many "win-win" opportunities, as sports venues regularly host huge numbers of
      spectators, offering food and entertainment, providing hours of exposure, and
      introducing new ideas for engaging fans in order to remain a competitive draw. In
      2008, the San Diego Padres embarked on a communitywide fitness initiative,
      FriarFit, including incorporating 10-minute Instant Recess breaks during their
      Sunday homestand pre-game shows. Many lessons have been learned that may be
      useful to others mounting such initiatives, such as: there is more at stake in
      cost-benefit and risk-benefit assessment for sports executives, requiring greater
      caution and circumspection than is typical for public health projects; the core
      business of the corporate entity must be accommodated without undermining the
      health objectives; and health aims must be addressed in a way that is financially
      viable and delivers tangible value for profit-making concerns, in terms of
      marketing, revenues or brand enhancement.

PMID- 19595705
TI  - Reference noise method of removing powerline noise from recorded signals.
AB  - Powerline contamination of recorded signals represents a major source of noise in
      electrophysiology and impairs the use of recordings for research. In this article
      we present simple and effective method for cancelling 50 Hz (or 60 Hz) noise
      using a reference noise signal and average noise cycle subtraction. This method
      is capable of reliably removing not only the fundamental powerline frequency but
      also its harmonic frequencies. The efficiency of this method appears to be
      superior to other commonly used methods such as notch filtering or adaptive
      filtering. Our experience and results show that this method can be efficiently
      used with very low signal-to-noise ratios, while preserving original signal
      waveform.

PMID- 19595704
TI  - Morphological changes do not reflect biochemical and functional differentiation
      in OLN-93 oligodendroglial cells.
AB  - OLN-93 cells, a cell line established from spontaneously transformed rat brain
      glial cultures, are used as a model for oligodendrocytes. These cells are known
      to undergo morphological changes upon serum deprivation. The objective of the
      present study is to investigate a possible correlation between these
      morphological changes and (1) the loss or gain of oligodendrocyte markers and (2)
      the electrophysiological properties of these cells. Using RT-PCR and
      immunocytochemistry, we demonstrate that the OLN-93 cell line expresses a broad
      range of markers (NG2, CNP, MAG, MOG) both when cultured in medium containing 10%
      or 0.5% fetal calf serum. Whole-cell patch-clamp recordings demonstrate that,
      regardless of the culture conditions, OLN-93 cells mainly express delayed
      rectifying K+ currents, a characteristic of immature oligodendrocytes. These
      currents are in part mediated by the shaker family of voltage-gated potassium
      channels. Kv1.1 and Kv1.3-expression are present at the mRNA and at the protein
      levels, and functional evidence for Kv1.3 mediated currents was obtained by using
      the selective blocker margatoxin. Under low serum conditions, OLN-93 cells
      exhibit differentiation-like morphological changes. However, we provide evidence
      that these morphological modifications do not necessarily correlate with
      biochemical or functional changes. Based on these data, we conclude that the OLN
      93 cell line can be situated at a developmental stage between a late pre
      oligodendrocyte and a late immature oligodendrocyte, regardless of serum
      concentration.

PMID- 19595706
TI  - Comment on "Functional consequences of Kv1.3 ion channel rearrangement into the
      immunological synapse".
AB  - Modulation of the biophysical properties of potassium channel currents upon
      immunological synapse formation between T cells and antigen-presenting cells has
      been reported. Some comments on this work are discussed in the light of
      previously described TASK channels on T lymphocytes.

PMID- 19595703
TI  - The mechanism of life-threatening water imbalance in schizophrenia and its
      relationship to the underlying psychiatric illness.
AB  - Impaired water excretion was noted to coincide with psychotic exacerbations in
      the first decades of the past century. In the ensuing decades, life-threatening
      water intoxication and elevated plasma levels of the antidiuretic hormone,
      arginine vasopressin (AVP) were reported in a subset of persons with
      schizophrenia. Subsequent studies demonstrated that the osmotic set point for AVP
      secretion was transiently reset in these patients by an unknown process and that
      this was further exacerbated by acute psychosis. More recent studies indicate
      that the AVP dysfunction is a manifestation of a hippocampal-mediated impairment
      in the regulation of both AVP and HPA axis responses to psychological, but not
      other types of, stimuli. Of potential significance, is that schizophrenic
      patients without water imbalance exhibit the opposite pattern of responses.
      Preliminary data indicate those with water imbalance also demonstrate a closely
      linked deficit in central oxytocin activity which may account for their
      diminished social function. These latter behavioral deficits are perhaps the most
      disabling and treatment resistant features of schizophrenia, which recent studies
      suggest, may respond to oxytocin agonists. Together these findings support the
      view that schizophrenia is a heterogeneous disorder, and provide novel biomarkers
      and approaches for exploring the pathophysiology and treatment of severe mental
      illness.

PMID- 19595708
TI  - Endothelial dysfunction induced by triglycerides is not restored by exenatide in
      rat conduit arteries ex vivo.
AB  - Exenatide (synthetic exendin-4) is a stable analogue of glucagon-like peptide 1
      (GLP-1) and has recently been approved for clinical use against type 2 diabetes.
      Exenatide is believed to exert its effects via the GLP-1 receptor with almost the
      same potency as GLP-1 in terms of lowering blood glucose. Short term exenatide
      treatment normalizes the altered vascular tone in type 2 diabetic rats, probably
      due to the reduction in glycemia. The aim of this study was to investigate
      whether exenatide directly protects against triglyceride-induced endothelial
      dysfunction in rat femoral arterial rings ex vivo. Short term pre-incubation with
      Intralipid (0.5 and 2%) was found to dose-dependently induce endothelial
      dysfunction, in that it elicited a significant reduction in ACh-induced
      vasorelaxation by 29% and 35%, respectively. Paradoxically, this occurred with a
      concomitant increase in endothelial nitric oxide synthase (eNOS) activity. No
      such reduction in vasorelaxation by Intralipid was seen in response to the NO
      donor sodium nitroprusside (SNP), revealing an endothelium-dependent vascular
      dysfunction by Intralipid. However, exenatide did not protect against Intralipid
      induced endothelial dysfunction. More surprisingly, the maximum vasorelaxation
      induced by exenatide (without Intralipid was only 3+/-2%, compared to the 23+/
      4%, 38+/-4%, 79+/-3% and 97+/-4% relaxations induced by GLP-1, GLP-1 (9-36), ACh
      and SNP, respectively. This unexpected finding prompted us to ascertain that the
      exenatide preparation was biologically active, and both exenatide (10(-11) mol/l)
      and GLP-1 (10(-9) mol/l) significantly increased insulin secretion in pancreatic
      beta-cells from ob/ob mice in vitro. In conclusion, exenatide could neither
      confer any acute protective effects against triglyceride-induced endothelial
      dysfunction nor exert any significant vasorelaxant actions in this model of rat
      conduit arteries ex vivo.

PMID- 19595707
TI  - Fentanyl, but not haloperidol, entrains persisting circadian activity episodes
      when administered at 24- and 31-h intervals.
AB  - Administration of several drugs of abuse on a 24-h schedule has been shown to
      entrain both pre-drug (anticipatory) and post-drug (evoked) circadian activity
      episodes that persist for several days when the drug is withheld. The present
      study tested the entrainment effects of fentanyl, an opioid agonist with a noted
      abuse liability, and haloperidol, an anti-psychotic dopamine antagonist without
      apparent abuse liability. Adult female Sprague-Dawley rats housed under constant
      light in cages with attached running wheels received repeated low, medium, or
      high doses of either fentanyl or haloperidol on a 24-h administration schedule
      followed by a 31-h schedule (Experiment 1) or solely on a 31-h schedule
      (Experiment 2). The results showed that all three doses of fentanyl entrained
      both pre-drug and post-drug episodes of wheel running when administered every
      24h, and the combined pre- and post-fentanyl activity episodes persisted for at
      least 3 days when the drug was withheld during test days. On the 31-h schedule,
      fentanyl produced an "ensuing" activity episode approximately 24h post
      administration, but failed to produce an anticipatory episode 29-31h post
      administration. In contrast, haloperidol injections failed to produce both pre
      drug episodes on the 24-h schedule and circadian ensuing episodes on the 31-h
      schedule, and post-haloperidol suppression of activity appeared to mask the free
      running activity rhythm. Taken together, these results provide additional
      evidence that drugs of abuse share a common ability to entrain circadian activity
      episodes.

PMID- 19595709
TI  - Involvement of the intermediate nucleus of the lateral septal area on angiotensin
      II-induced dipsogenic and pressor responses.
AB  - Previous studies have shown that different parts of the septal area may have
      opposite roles in the control of water intake and cardiovascular responses. In
      the present study we investigated the effects of electrolytic lesions of the
      intermediate nucleus of the lateral septal area (LSI) on cardiovascular and
      dipsogenic responses to intracerebroventricular (icv) angiotensin II (ANG II) and
      water intake induced by other different stimuli. Male Holtzman rats (280-320 g of
      body weight, n=6-16/group) with sham or electrolytic lesions of the LSI and a
      stainless steel cannula implanted into the lateral ventricle (LV) were used. The
      LSI lesions did not affect body weight or daily water intake. However, LSI
      lesions reduced water intake and pressor responses induced by icv ANG II (4.10(
      2) nmol). The LSI lesions also slightly reduced water intake induced by 24 h of
      water deprivation or isoproterenol (30 microg/kg) subcutaneously, but did not
      affect water intake induced by intragastric 2 ml of 2 M NaCl load. The results
      suggest that LSI is part of the forebrain circuitry activated by ANG II to
      produce pressor and dipsogenic responses. However, the same nucleus is not
      involved in the dipsogenic responses to central osmoreceptor activation.

PMID- 19595710
TI  - Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c
      Met/HGF receptor contributes disease retardation of a transgenic mouse model of
      ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by
      progressive degeneration of motoneurons. We have demonstrated that hepatocyte
      growth factor (HGF) attenuates loss of both spinal and brainstem motoneurons of
      ALS model mice expressing mutated human SOD1(G93A) (G93A). This study was
      designed to assess disease-dependent regulatory mechanisms of c-Met/HGF receptor
      (c-Met) activation in the facial motoneurons of G93A mice. Using double
      transgenic mice expressing HGF and mutated SOD1(G93A) (G93A/HGF), we showed that
      phosphorylation of c-Met tyrosine residues at positions 1230, 1234 and 1235
      (phospho-Tyr), and thereby its activation, was slightly evident in G93A and
      highly obvious in G93A/HGF mice (but absent in WT and HGF-Tg mice).
      Phosphorylation of the c-Met serine residue at position 985 (phospho-Ser), a
      residue involved in the negative regulation of its activation, was evident in WT
      and HGF-Tg mice. Protein phosphatase 2A (PP2A), which is capable of
      dephosphorylating c-Met phospho-serine, is upregulated in the facial motoneurons
      of G93A and G93A/HGF mice compared with WT and HGF-Tg mice. Thus, c-Met
      activation is reciprocally regulated by phosphorylation between c-Met serine and
      tyrosine residues through PP2A induction in the presence or absence of mutant
      SOD1 expression, and HGF functions more efficiently in ALS and ALS-related
      diseases.

PMID- 19595711
TI  - SR proteins in vertical integration of gene expression from transcription to RNA
      processing to translation.
AB  - SR proteins have been studied extensively as a family of RNA-binding proteins
      that participate in both constitutive and regulated pre-mRNA splicing in
      mammalian cells. However, SR proteins were first discovered as factors that
      interact with transcriptionally active chromatin. Recent studies have now
      uncovered properties that connect these once apparently disparate functions,
      showing that a subset of SR proteins seem to bind directly to the histone 3 tail,
      play an active role in transcriptional elongation, and colocalize with genes that
      are engaged in specific intra- and interchromosome interactions for coordinated
      regulation of gene expression in the nucleus. These transcription-related
      activities are also coupled with a further expansion of putative functions of
      specific SR protein family members in RNA metabolism downstream of mRNA splicing,
      from RNA export to stability control to translation. These findings, therefore,
      highlight the broader roles of SR proteins in vertical integration of gene
      expression and provide mechanistic insights into their contributions to genome
      stability and proper cell-cycle progression in higher eukaryotic cells.

PMID- 19595712
TI  - FAK phosphorylation by ERK primes ras-induced tyrosine dephosphorylation of FAK
      mediated by PIN1 and PTP-PEST.
AB  - Activated Ras has been found in many types of cancer. However, the mechanism
      underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here
      that activated Ras induces tyrosine dephosphorylation and inhibition of FAK
      mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK
      phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK
      at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of
      FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of
      FAK mediated by this signal relay promotes Ras-induced cell migration, invasion,
      and metastasis. These findings uncover the importance of sequential modification
      of FAK-by serine phosphorylation, isomerization, and tyrosine dephosphorylation-
      in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.

PMID- 19595713
TI  - TACE-mediated ectodomain shedding of the type I TGF-beta receptor downregulates
      TGF-beta signaling.
AB  - Regulating TGF-beta receptor presentation provides an avenue to alter a cell's
      responsiveness to TGF-beta. We report that activation of the Erk MAP kinase
      pathway decreases the TGF-beta-induced Smad3 activation due to decreased cell
      surface levels of the type I receptor TbetaRI, but not the type II receptor.
      Inhibition of TACE activity or expression enhanced the cell surface TbetaRI
      levels and TGF-beta-induced Smad3 and Akt activation. Accordingly, silencing TACE
      expression in cancer cells enhanced the TbetaRI presentation and TGF-beta
      responsiveness, including the antiproliferative effect of TGF-beta, and
      epithelial-to-mesenchymal transition. These results establish a mechanism for
      downregulating TGF-beta signaling through TACE activation by the Erk MAP kinase
      pathway and a strategy for evasion of tumor suppression and modulation of
      epithelial-to-mesenchymal transition during cancer progression. The decreased
      growth inhibition by TGF-beta, due to elevated TACE activity, complements the
      growth stimulation resulting from increased release of TGF-alpha family ligands.

PMID- 19595714
TI  - GTP hydrolysis by IF2 guides progression of the ribosome into elongation.
AB  - Recent structural data have revealed two distinct conformations of the ribosome
      during initiation. We employed single-molecule fluorescence methods to probe the
      dynamic relation of these ribosomal conformations in real time. In the absence of
      initiation factors, the ribosome assembles in two distinct conformations. The
      initiation factors guide progression of the ribosome to the conformation that can
      enter the elongation cycle. In particular, IF2 both accelerates the rate of
      subunit joining and actively promotes the transition to the elongation-competent
      conformation. Blocking GTP hydrolysis by IF2 results in 70S complexes formed in
      the conformation unable to enter elongation. We observe that rapid GTP hydrolysis
      by IF2 drives the transition to the elongation-competent conformation, thus
      committing the ribosome to enter the elongation cycle.

PMID- 19595715
TI  - Transcriptional integration of TLR2 and TLR4 signaling at the NCoR derepression
      checkpoint.
AB  - Activation of toll-like receptors (TLRs) leads to derepression and subsequent
      activation of inflammatory response genes that play essential roles in innate and
      acquired immunity. Derepression requires signal-dependent turnover of the nuclear
      receptor corepressor NCoR from target promoters, but the mechanisms remain poorly
      understood. Here, we report that TLR4 uses NFkappaB to deliver IKKepsilon to
      target promoters that contain "integrated circuits" of kappaB and AP-1 sites,
      resulting in local phosphorylation of c-Jun and subsequent NCoR clearance. In
      contrast, TLR2 signaling leads to rapid activation of CaMKII and phosphorylation
      of the TBLR1 component of NCoR complexes, bypassing the requirement for c-Jun
      phosphorylation and enabling NCoR clearance from promoters lacking integrated
      kappaB elements. Intriguingly, the IKKvarepsilon-dependent clearance pathway is
      sensitive to transrepression by liver X receptors, while the CaMKII-dependent
      pathway is not. These findings reveal mechanisms for integration of TLR, calcium,
      and nuclear receptor signaling pathways that underlie pathogen-specific responses
      and disease-specific programs of inflammation.

PMID- 19595716
TI  - Conformational changes associated with template commitment in ATP-dependent
      chromatin remodeling by ISW2.
AB  - Distinct stages in ATP-dependent chromatin remodeling are found as ISW2, an ISWI
      type complex, forms a stable and processive complex with nucleosomes upon
      hydrolysis of ATP. There are two conformational changes of the ISW2-nucleosome
      complex associated with binding and hydrolysis of ATP. The initial binding of
      ISW2 to extranucleosomal DNA, to the entry site, and near the dyad axis of the
      nucleosome is enhanced by ATP binding, whereas subsequent ATP hydrolysis is
      required for template commitment and causes ISW2 to expand its interactions with
      nucleosomal DNA to an entire gyre of the nucleosome and a short approximately 3-4
      bp site on the other gyre. The histone-fold-like subunit Dpb4 associates with
      nucleosomal DNA approximately 15 bp from the ATPase domain as part of this change
      and may help to disrupt histone-DNA interactions. These additional contacts are
      independent of the ATPase domain tracking along nucleosomal DNA and are
      maintained as ISW2 moves nucleosomes on DNA.

PMID- 19595717
TI  - Multiple pathways regulate 3' overhang generation at S. cerevisiae telomeres.
AB  - Generation of 3' G strand overhangs at telomere ends may play a role in
      regulating telomerase action and occurs by still unclear mechanisms. We show by
      an inducible short telomere assay that Sae2 and the Sgs1 RecQ helicase control
      two distinct but partially complementary pathways for nucleolytic processing of
      S. cerevisiae telomeres, with Sae2 function requiring its serine 267
      phosphorylation. No processing activity is detectable in sae2Delta sgs1Delta
      cells, while the Exo1 exonuclease contributes to telomere end processing and
      elongation in both sae2Delta and sgs1Delta cells, suggesting that Exo1 telomeric
      function requires either Sgs1 or Sae2 action. Moreover, Dna2 might also support
      Sgs1 activity, as it acts redundantly with Exo1, but not with Sgs1. Finally, both
      length maintenance and G strand overhang generation at native telomeres are
      affected in sae2Delta sgs1Delta cells, further supporting the notion that Sae2
      and Sgs1 combined activities control telomere length by regulating telomere
      processing.

PMID- 19595718
TI  - Large-scale expansions of Friedreich's ataxia GAA repeats in yeast.
AB  - Large-scale expansions of DNA repeats are implicated in numerous hereditary
      disorders in humans. We describe a yeast experimental system to analyze large
      scale expansions of triplet GAA repeats responsible for the human disease
      Friedreich's ataxia. When GAA repeats were placed into an intron of the chimeric
      URA3 gene, their expansions caused gene inactivation, which was detected on the
      selective media. We found that the rates of expansions of GAA repeats increased
      exponentially with their lengths. These rates were only mildly dependent on the
      repeat's orientation within the replicon, whereas the repeat-mediated replication
      fork stalling was exquisitely orientation dependent. Expansion rates were
      significantly elevated upon inactivation of the replication fork stabilizers,
      Tof1 and Csm3, but decreased in the knockouts of postreplication DNA repair
      proteins, Rad6 and Rad5, and the DNA helicase Sgs1. We propose a model for large
      scale repeat expansions based on template switching during replication fork
      progression through repetitive DNA.

PMID- 19595719
TI  - Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for
      the ubiquitin ligase CRL4Cdt2.
AB  - Substrates of the E3 ubiquitin ligase CRL4(Cdt2), including Cdt1 and p21, contain
      a PCNA-binding motif called a PIP box. Upon binding of the PIP box to PCNA on
      chromatin, CRL4(Cdt2) is recruited and the substrate is ubiquitylated.
      Importantly, a PIP box cannot be sufficient for destruction, as most PIP box
      proteins are stable. Using Xenopus egg extracts, we identify two sequence
      elements in CRL4(Cdt2) substrates that promote their proteolysis: a specialized
      PIP box that confers exceptionally efficient PCNA binding and a basic amino acid
      4 residues downstream of the PIP box, which recruits CRL4(Cdt2) to the substrate
      PCNA complex. We also identify two mechanisms that couple CRL4(Cdt2)-dependent
      proteolysis to the chromatin-bound form of PCNA, ensuring that this proteolysis
      pathway is active only in S phase or after DNA damage. Thus, CRL4(Cdt2)
      recognizes an unusual degron, which is assembled specifically on chromatin via
      the binding of a specialized PIP box to PCNA.

PMID- 19595720
TI  - Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP
      turnover and dissociation of Rad51 from DNA.
AB  - Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks
      and the generation of genetic diversity by homologous recombination (HR). In the
      presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded
      DNA to catalyze strand exchange. Inappropriate HR causes genomic instability, and
      it is normally prevented by remodeling enzymes that antagonize the activities of
      Rad51 nucleoprotein filaments. In yeast, the Srs2 helicase/translocase suppresses
      HR by clearing Rad51 polymers from single-stranded DNA. We have examined the
      mechanism of disassembly of Rad51 nucleoprotein filaments by Srs2 and find that a
      physical interaction between Rad51 and the C-terminal region of Srs2 triggers ATP
      hydrolysis within the Rad51 filament, causing Rad51 to dissociate from DNA. This
      allosteric mechanism explains the biological specialization of Srs2 as a DNA
      motor protein that antagonizes HR.

PMID- 19595721
TI  - Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for
      DNA repair.
AB  - Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to
      ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1
      Rad10 endonuclease to control cleavage of 3' flaps during repair of double-strand
      breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for
      DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates
      show SLX1-dependent nuclease activity toward Holliday junctions and MUS81
      dependent activity toward other branched DNA structures. Furthermore, SLX4
      enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in
      processing recombination intermediates, cells depleted of SLX4 are hypersensitive
      to genotoxins that cause DSBs and show defects in the resolution of interstrand
      crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced
      homologous recombination. These data show that SLX4 is a regulator of structure
      specific nucleases and that SLX4 and SLX1 are important regulators of genome
      stability in human cells.

PMID- 19595723
TI  - Participation of the phosphatidylinositol 3-kinase/Akt pathway in Junin virus
      replication in vitro.
AB  - In this paper we demonstrate that infection of cell cultures with the arenavirus
      Junin (JUNV), agent of the argentine haemorrhagic fever, leads to the activation
      of PI3K/Akt signalling pathway. Phosphorylation of Akt occurs early during JUNV
      infection of Vero cells and is blocked by the PI3K inhibitor, Ly294002. Infection
      of cells with UV-irradiated JUNV redeemed the pattern of stimulation observed for
      infectious virus indicating that an early stage of multiplication cycle would be
      enough to trigger activation. Treatment of cells with chlorpromazine abrogated
      phosphorylation of Akt upon JUNV infection suggesting virus internalization as
      responsible for activation. Inhibition of Akt phosphorylation by Ly294002
      impaired viral protein synthesis and expression leading to a reduced infectious
      virus yield without blocking the onset of persistent stage of infection. This
      impairment is linked to a reduced amount of virus bound to cells probably due to
      a blockage on the recycling of transferrin cell-receptor, employed by the virus
      to adsorb to the cell surface. Early Akt activation was also observed in BHK-21
      and A549 JUNV infected cells suggesting an important role of PI3K/Akt signalling
      in JUNV multiplication in vitro.

PMID- 19595722
TI  - Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure
      specific endonucleases in DNA repair and recombination.
AB  - DNA recombination and repair pathways require structure-specific endonucleases to
      process DNA structures that include forks, flaps, and Holliday junctions.
      Previously, we determined that the Drosophila MEI-9-ERCC1 endonuclease interacts
      with the MUS312 protein to produce meiotic crossovers, and that MUS312 has a MEI
      9-independent role in interstrand crosslink (ICL) repair. The importance of
      MUS312 to pathways crucial for maintaining genomic stability in Drosophila
      prompted us to search for orthologs in other organisms. Based on sequence,
      expression pattern, conserved protein-protein interactions, and ICL repair
      function, we determined that the mammalian ortholog of MUS312 is BTBD12.
      Orthology between these proteins and S. cerevisiae Slx4 helped identify a
      conserved interaction with a second structure-specific endonuclease, SLX1.
      Genetic and biochemical evidence described here and in related papers suggest
      that MUS312 and BTBD12 direct Holliday junction resolution by at least two
      distinct endonucleases in different recombination and repair contexts.

PMID- 19595724
TI  - Convenient targeting of stealth siRNA-lipoplexes to cells with chelator lipid
      anchored molecules.
AB  - A major obstacle for the use of siRNAs as novel therapeutics is the requirement
      for functional delivery to specific cells in vivo. siRNA delivery by cationic
      agents is generally non-specific and a convenient targeting strategy has been
      lacking. This work explored the potential for using the chelator lipid
      3(nitrilotriacetic acid)-ditetradecylamine (NTA(3)-DTDA) with neutral stealth
      liposomes to target siRNA to cells. A novel method for incorporating siRNAs into
      lipoplexes was developed which utilised helper lipids and the ionisable lipid 1,2
      dioleoyl-3-dimethylammonium-propane (DODAP). This approach results in an
      efficient (>50%) incorporation of siRNA into lipoplexes, which when incorporated
      with Ni-NTA(3)-DTDA and engrafted with a His-tagged form of murine CD4 can target
      siRNA to murine A20 B cells, in vitro. Also, siRNA-lipoplexes engrafted with His
      tagged peptides that target receptors on HEK-293 cells, or the receptor for
      tumour necrosis factor alpha expressed on the murine dendritic cell line DC2.4,
      could target siRNA and silence the expression of enhanced green fluorescence
      protein (EGFP). siRNA-lipoplexes produced by this method are approximately 240 nm
      dia, exhibit low zeta-potential (-1 mV), and target cells in serum-containing
      media. The results show that NTA(3)-DTDA can be used to target siRNA-lipoplexes
      to cells, and could provide a convenient approach for targeting siRNA to cells in
      vivo for therapeutic applications.

PMID- 19595725
TI  - Perimenstrual chocolate craving. What happens after menopause?
AB  - About half of American women crave chocolate, and approximately half of the
      cravers crave it specifically around the onset of menstruation. This study
      examines whether the primary cause of this "perimenstrual" craving is a direct
      effect of hormonal changes around the perimenstrum, or rather if the craving is a
      general response in some individuals to stress or other notable events. Insofar
      as there is a direct hormonal effect, one would predict a substantial decrease of
      38% in total chocolate craving in women post-menopause, corresponding to the
      proportion of women pre-menopause who report craving chocolate exclusively
      perimenstrually. Based on a survey of pre- and post-menopausal alumnae of the
      same University, we report a significant but small decrease in prevalence of
      chocolate cravings post-menopause. The decrease is only 13.4% and thereby much
      smaller than a 38% drop predicted by a purely hormonal explanation, suggesting
      that female reproductive hormones are not the principal cause of perimenstrual
      chocolate craving.

PMID- 19595726
TI  - Identification of novel I-superfamily conopeptides from several clades of Conus
      species found in the South China Sea.
AB  - The I-superfamily of Conus peptides represents a new class of peptides with four
      disulfide bridges (-C-C-CC-CC-C-C-) that falls into three (I1, I2 and I3)
      categories according to the different signal peptide sequences. The I-superfamily
      has received increasing attention because it targets K+ ion channels, a function
      that is relatively rare in conotoxins. Herein we report 11 novel I-superfamily
      conotoxins from the venom ducts of five Cone snails (Conus eburneus, Conus
      imperialis, Conus vitulinus, Conus emaciatus and Conus litteratus) native to the
      South China Sea using a primer designed according to the N-terminus of the signal
      sequence of I2-superfamily conotoxins. The alignment of sequences revealed that
      signal regions exhibited moderate conservation with the exception of Eb11.3 from
      C. eburneus with homologies of 21.1%, 38.5% and 30.0% to the signal peptides of
      I1, I2 and I3 superfamily conotoxins, respectively. The mature peptides ranged
      from almost identical to highly divergent between species. Analyses of the
      evolutionary trees of these peptides with those of reported I-superfamily
      conotoxins showed that nine of them fall in I2 superfamily clades, but two of
      them were neither I1- and I2- nor I3-superfamily clades. Notably, some peptides
      exhibited significantly different amino acid residues in the intercysteine loops
      compared with group A, B and C of I-superfamily conopeptides, suggesting that
      they may have different bioactivities and functions.

PMID- 19595727
TI  - Ghrelin and its therapeutic potential for cachectic patients.
AB  - The discovery of ghrelin has resulted in the development of approaches to
      appetite, enabling a better understanding of the mechanisms regulating appetite
      through molecular analyses. Ghrelin is a 28-amino acid peptide that was isolated
      from the stomach only a decade ago, and has recently been investigated as a
      potential therapeutic endogenous agent. This peptide increases appetite, adjusts
      energy balance, suppresses inflammation, and enhances the release of growth
      hormone from the pituitary gland. Although many bioactive substances such as
      peptide YY, leptin, adiponectin and obestatin are involved in appetite control,
      ghrelin is the only known peptide to signal starvation information from a
      peripheral organ to the central nervous system, contributing to an increase in
      appetite. Clinical trials have revealed the effectiveness of ghrelin in
      increasing lean body mass and activity in cachectic patients. As shown in
      clinical research on humans and basic research using animal models, cachexia
      often occurs in response to excess release of proinflammatory cytokines and
      induces further appetite loss, which aggravates the physiological status of
      underlying diseases. Ghrelin functions as a protector against the vicious cycle
      of the cachectic paradigm through orexigenic, anabolic and anti-inflammatory
      effects, so administration of ghrelin may be able to improve quality of life in
      cachectic patients. We show here a significant role of ghrelin in the
      pathophysiology of cachectic diseases and the possibility of clinical
      applications.

PMID- 19595728
TI  - Seven decades of angiotensin (1939-2009).
AB  - Two research groups in both North and South America independently discovered that
      renin released a novel vasopressor agent. The Argentine group named it
      hypertensin, and called its plasma protein substrate hypertensinogen. The group
      from the United States named it angiotonin. In 1958, Braun Menendez and Irvine
      Page suggested that the peptide should be named angiotensin. The combined name
      eventually became commonly used to avoid linguistic confusion. Research
      scientists and physicians today acknowledge that studies of the renin-angiotensin
      system (RAS) have greatly improved our understanding of several diseases.
      Certainly, medical practice profited significantly from the synthesis and
      application of numerous pharmacological agents that antagonize either the
      biosynthesis or pharmacological responses of endogenously generated angiotensin
      II. Ultimately, discovery of the renin-angiotensin system led to many studies
      that resulted in therapies for vascular disease. This article briefly reviews
      research related to the discovery of angiotensin and indicates the importance of
      additional studies related to the RAS.

PMID- 19595729
TI  - Transthyretin knockout mice display decreased susceptibility to AMPA-induced
      neurodegeneration.
AB  - Transthyretin (TTR) has been regarded as a neuroprotective protein given that TTR
      knockout (KO) mice display increased susceptibility for amyloid beta deposition
      and memory deficits during aging. In parallel, TTR KO mice have increased levels
      of neuropeptide Y (NPY), which promotes neuroprotection and neuroproliferation.
      In this work, we aimed at evaluating TTR neuroprotective effect against an
      excitotoxic insult that is known to be prevented by NPY action. We show that
      despite a putative neuroprotective role of TTR, hippocampal slice cultures from
      TTR KO mice display a decreased susceptibility to AMPA-induced neurodegeneration.
      We also suggest that increased NPY levels in TTR KO mice are not associated with
      increased cell proliferation in the dentate gyrus or subventricular zone. In
      summary, the alleged neuroprotective role of TTR in the nervous system should be
      regarded with caution and should not be generalized to all types of insults.

PMID- 19595732
TI  - Studies on the antioxidant activity of essential oil and different solvent
      extracts of Vitexagnuscastus L. fruits from Turkey.
AB  - This study is designed to examine the chemical composition and antioxidant
      activity of the essential oil and different solvent extracts of Vitexagnuscastus.
      GC and GC-MS analysis was resulted in the detection of 27 components,
      representing 94.5% of the oil. Major components of the oil were 1,8-cineole
      (24.98%), sabinene (13.45%), alpha-pinene (10.60%), alpha-terpinyl acetate
      (6.66%), and (Z)-beta-farnesene (5.40%). Antioxidant activities of the samples
      were determined by three different test systems, DPPH, beta-carotene/linoleic
      acid and reducing power assays. In all systems, water extract exhibited excellent
      activity potential than those of other extracts (hexane, dichloromethane, ethyl
      acetate and methanol) and the oil. As expected, amount of total phenolics was
      very high in this extract (112.46+/-1.22mugGAEs/mgextract). Dichloromethane
      extract has been found to be rich in flavonoids. A positive correlation was
      observed between the antioxidant activity potential and total phenolic and
      flavonoid levels of the extracts.

PMID- 19595733
TI  - Polyamine transporter recognization and antitumor effects of anthracenymethyl
      homospermidine.
AB  - This study was conducted to examine the polyamine transporter (PAT) recognization
      and antitumor effects of anthracenymethyl homospermidine (ANTMHspd) and its
      apoptotic mechanism in B16 melanoma cells. ANTMHspd promoted a dose-dependent
      apoptosis in B16 melanoma cells and the apoptosis was associated with the
      excellent PAT recognization, externalization of cell membrane phosphatidylserine
      and the disruption of mitochondria, these processes were correlated with up
      regulation of polyamine oxidase, an increase in intracellular reactive oxygen
      species (ROS) production and oxidative stress. In addition, reduction of MMP,
      release of cytochrome c, up-regulation of Bax protein expression, down-regulation
      of Bcl-2 protein expression, and activation of caspase-3, caspase-9 were also
      observed in B16 cells after treatment with ANTMHspd. Furthermore, N
      acetylcysteine obviously antagonized ANTMHspd-induced apoptosis. Importantly,
      ANTMHspd was found to be better tolerated and revealed potent antitumor effect on
      inhibiting tumor growth in situ and suppressing pulmonary metastasis in xenograft
      mice model. These data demonstrate that ANTMHspd is an excellent PAT
      recognization and potent antitumor agent.

PMID- 19595731
TI  - Selective participation of the bed nucleus of the stria terminalis and CRF in
      sustained anxiety-like versus phasic fear-like responses.
AB  - The medial division of the central nucleus of the amygdala (CeA(M)) and the
      lateral division of the bed nucleus of the stria terminalis (BNST(L)) are closely
      related. Both receive projections from the basolateral amygdala (BLA) and both
      project to brain areas that mediate fear-influenced behaviors. In contrast to
      CeA(M) however, initial attempts to implicate the BNST in conditioned fear
      responses were largely unsuccessful. More recent studies have shown that the BNST
      does participate in some types of anxiety and stress responses. Here, we review
      evidence suggesting that the CeA(M) and BNST(L) are functionally complementary,
      with CeA(M) mediating short- but not long-duration threat responses (i.e., phasic
      fear) and BNST(L) mediating long- but not short-duration responses (sustained
      fear or 'anxiety'). We also review findings implicating the stress-related
      peptide corticotropin-releasing factor (CRF) in sustained but not phasic threat
      responses, and attempt to integrate these findings into a neural circuit model
      which accounts for these and related observations.

PMID- 19595735
TI  - Somatostatin, Alzheimer's disease and cognition: an old story coming of age?
AB  - In mammalian brain, the somatostatin (SRIF: somatotropin release-inhibiting
      factor) family is composed of two peptides: SRIF and cortistatin (CST), which
      interact with five different receptor subtypes, sst(1-5). This review summarizes
      the properties of these receptors, the involvement of somatostatinergic systems
      in Alzheimer's disease (SRIF/acetylcholine (Ach), SRIF/amyloid beta peptides, and
      SRIF/tau interactions) and their role in cognition from early studies using
      cysteamine as an SRIF depleting substance to the use of subtype selective
      analogues and knockout mice, and modulation of synaptic plasticity. The current
      SRIF story illustrates how cognition and emotion are intimately integrated in
      brain function.

PMID- 19595736
TI  - Neuroactive steroid regulation of neurotransmitter release in the CNS: action,
      mechanism and possible significance.
AB  - Neuroactive steroids refer to steroids that are capable of regulating neuronal
      activities. Neuroactive steroids, synthesized either de novo in the nervous
      tissue or in the peripheral endocrine glands or as synthetic steroids, have
      exhibited numerous important modulatory effects on brain functions and brain
      diseases. At the cellular level, in addition to the effect on postsynaptic
      receptors, most neuroactive steroids, including pregnenolone, pregnenolone
      sulfate, progesterone, allopregnanolone, dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, testosterone and estradiol, have modulatory
      effects on the release of multiple neurotransmitters like glutamate, GABA,
      acetylcholine, norepinephrine, dopamine and 5-HT. Many of these effects occur in
      the brain regions involved in learning and memory, emotion, motivation, motor and
      cognition. Moreover, the effects are rather complicated, maybe depending on many
      factors such as types of neuroactive steroids, brain regions and presynaptic
      functional states. The mechanisms are also complicated. Many of them involve
      rapid non-genomic effects on presynaptic receptors and ion channels like sigma-1
      receptor, alpha(1) receptor, nicotine receptor, D1 receptor, NMDA receptor,
      GABA(A) receptor and L-type Ca(2+) channels. These effects have made neuroactive
      steroids important regulators of synaptic transmission in the central nervous
      system and constitute the major basis for many important actions of neuroactive
      steroids on brain functions and brain diseases.

PMID- 19595734
TI  - Identification of the putative tumor suppressor Nit2 as omega-amidase, an enzyme
      metabolically linked to glutamine and asparagine transamination.
AB  - The present report identifies the enzymatic substrates of a member of the
      mammalian nitrilase-like (Nit) family. Nit2, which is widely distributed in
      nature, has been suggested to be a tumor suppressor protein. The protein was
      assumed to be an amidase based on sequence homology to other amidases and on the
      presence of a putative amidase-like active site. This assumption was recently
      confirmed by the publication of the crystal structure of mouse Nit2. However, the
      in vivo substrates were not previously identified. Here we report that rat liver
      Nit2 is omega-amidodicarboxylate amidohydrolase (E.C. 3.5.1.3; abbreviated omega
      amidase), a ubiquitously expressed enzyme that catalyzes a variety of amidase,
      transamidase, esterase and transesterification reactions. The in vivo amidase
      substrates are alpha-ketoglutaramate and alpha-ketosuccinamate, generated by
      transamination of glutamine and asparagine, respectively. Glutamine transaminases
      serve to salvage a number of alpha-keto acids generated through non-specific
      transamination reactions (particularly those of the essential amino acids).
      Asparagine transamination appears to be useful in mitochondrial metabolism and in
      photorespiration. Glutamine transaminases play a particularly important role in
      transaminating alpha-keto-gamma-methiolbutyrate, a key component of the
      methionine salvage pathway. Some evidence suggests that excess alpha
      ketoglutaramate may be neurotoxic. Moreover, alpha-ketosuccinamate is unstable
      and is readily converted to a number of hetero-aromatic compounds that may be
      toxic. Thus, an important role of omega-amidase is to remove potentially toxic
      intermediates by converting alpha-ketoglutaramate and alpha-ketosuccinamate to
      biologically useful alpha-ketoglutarate and oxaloacetate, respectively. Despite
      its importance in nitrogen and sulfur metabolism, the biochemical significance of
      omega-amidase has been largely overlooked. Our report may provide clues regarding
      the nature of the biological amidase substrate(s) of Nit1 (another member of the
      Nit family), which is a well-established tumor suppressor protein), and
      emphasizes a) the crucial role of Nit2 in nitrogen and sulfur metabolism, and b)
      the possible link of Nit2 to cancer biology.

PMID- 19595737
TI  - Entropy decrease associated to solute compartmentalization in the cell.
AB  - We have deduced equations to quantify the entropy associated to the
      compartmentalization of components in eukaryotic cells as a function of cell and
      compartment volumes, and of the concentration of solutes. On the basis of known
      and plausible values of volume and solute concentrations and the deduced
      equations, we estimate that the contribution of compartmentalization to the
      decrease of entropy is approximately -14.4 x 10(-14)JK(-1)cell(-1) (-0.7 J K(
      1)L(-1)) in the case of Saccharomyces cerevisiae, a typical eukaryotic cell, and
      approximately -49.6 x 10(-14)JK(-1)cell(-1) (-1.0 J K(-1)L(-1)) in the more
      complex Chlamydomonas reinhardtii. When compared with other potential
      contributing factors, such as the informational entropy of DNA and the
      conformational entropy of proteins, compartmentalization appears as an essential
      development that significantly decreased the entropy of living cells during
      biological evolution.

PMID- 19595738
TI  - Early induced beta/gamma activity during illusory contour perception.
AB  - The temporal binding hypothesis proposes that visual feature binding is achieved
      by neuronal synchronization. Nevertheless, the existing human neurophysiological
      evidence for the neuronal synchronization in visual feature binding-the
      oscillatory induced beta/gamma activity (IB/GA) is under suspicion. The
      previously observed IB/GA occurs at a later stage (after 200 ms), thus leading to
      the objection that IB/GA may be related to some later top-down processes rather
      than the early perceptual processing. However, the present EEG study identified
      an IB/GA as early as 90 ms after stimulus onset, which was stronger for a Kanizsa
      type illusory contour (IC, a classic example of visual feature binding) than for
      a control stimulus. This finding provides new human evidence for the temporal
      binding hypothesis that neuronal synchronization occurs at the early stage of
      visual feature binding.

PMID- 19595739
TI  - Partial correlation investigation on the default mode network involved in
      acupuncture: an fMRI study.
AB  - Certain clinical reports and researches have shown that acupuncture effects can
      sustain a period during the post-stimulation state, and modulate the default mode
      network (DMN). In this study, partial correlation approach was utilized to
      investigate whether or not electro-acupuncture stimulation (EAS) at the three
      acupoints (GB37 (Guangming), BL60 (Kunlun) and KI8 (Jiaoxin)) and one sham point
      on the left leg modulated the DMN and how to change the intrinsic connectivity of
      the DMN. The results indicated that DMN could be modulated after EAS, and there
      existed different modulation patterns of the four points. Meanwhile, we found
      that the posterior cingulate cortex and precuneus (PCC/pC) strongly interacted
      with other nodes during the pre- and post-stimulation states. The correlation was
      interrupted between the PCC/pC and anterior cingulate cortex (ACC). The orbital
      prefrontal cortex (OFC) negatively interacted with the left medial temporal
      cortex (lMTC) at the acupoints. We suggested that the distinct modulation
      patterns to the DMN attributed to the different effects evoked by the three
      acupoints and one sham point.

PMID- 19595740
TI  - Different growth patterns of two adjacent glomeruli responsible for sex-pheromone
      processing during postembryonic development of the cockroach Periplaneta
      americana.
AB  - In many insect species, sex pheromone is processed by specific, enlarged
      glomeruli in the antennal lobes of males. In the male American cockroach, two
      closely located glomeruli (A and B) are responsible for processing the major
      pheromone components (periplanone-A and -B, respectively), and these collectively
      form the macroglomerular complex. Afferents originating from the dorsal and
      ventral surfaces of the antenna tend to project to the anterior and posterior
      regions of the macroglomerular complex via the dorsal and ventral antennal
      nerves, respectively. This topographic segregation of afferents is seen only in
      the macroglomerular complex, and not in other glomeruli that process normal
      environmental odors. Using differential, anterograde dye injection into the two
      antennal sensory nerves, we show that the macroglomerular complex is not formed
      by fusion of several glomeruli, as suggested in previous studies, but that the
      precursors of the A- and B-glomeruli already exist in the first larval instar.
      The volume of afferents in the macroglomerular complex precursor increases nearly
      exponentially with molting times, 430-fold from the first instar to the adult.
      The A- and B-glomeruli both undergo continuous growth during postembryonic
      development, but peak growth rates occur in different larval stages. The growth
      rate of the B-glomerulus peaked in the mid-developmental stage then declined,
      while growth of A-glomerulus was maintained at low level in early- to mid
      developmental stages but increased greatly in later stages. These results suggest
      perception of sex pheromone occurs in early instars, and that PA and PB have
      distinct roles in different developmental stages.

PMID- 19595741
TI  - Event-related potential correlates of the collective self-relevant effect.
AB  - The present study investigated the electrophysiological correlates of the
      psychological processing of the collective self-relevant stimulus using a three
      stimulus oddball paradigm. The results showed that P300 amplitude elicited by the
      collective self-relevant stimulus was larger than those elicited by familiar and
      unfamiliar stimuli. In addition, N250 and P300 amplitudes elicited by subjects'
      own names were larger than those elicited by other name stimuli. In terms of
      lateralization of P300, the collective self-relevant effect was largest in the
      left region sites and the individual self-relevant effect was largest in the
      right region sites. Therefore, the present study extended previous findings by
      showing that the collective self, similar to the famous individual self, was
      psychologically important to humans.

PMID- 19595742
TI  - Evidences of cannabinoids-induced modulation of paroxysmal events in an
      experimental model of partial epilepsy in the rat.
AB  - The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by
      the activation of the CB(1) receptor. This study evaluates the anticonvulsant
      activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3
      de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone
      or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1)
      antagonist) in an experimental in vivo model of complex partial seizures (maximal
      dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an
      anticonvulsant effect, significantly reduced by the pre-treatment with AM251
      (1mgkg(-1), 30 min interval). Surprisingly, AM251, administered alone at the same
      dose, failed to induce any modification in MDA responses. Our data suggest the
      involvement of the CB system in the inhibitory control of hyperexcitability
      phenomena in a model of acute partial epilepsy. Although the MDA model per se
      does not induce a basal activation of CB(1) receptors, as suggested by the lack
      of efficacy of AM251 when administered alone, the partial suppression of
      WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise
      that the WIN55,212-2-induced antiepileptic effect is strictly linked to an
      increased CB(1) receptor activation or to the involvement of further receptor
      subtypes.

PMID- 19595743
TI  - Interleukin-2 deficiency-induced T cell autoimmunity in the mouse brain.
AB  - Interleukin-2 (IL-2) has been implicated in the pathogenesis of
      neurodevelopmental and neurodegenerative disorders. Studies from our lab have
      shown that adult IL-2 knockout (KO) mice exhibit septohippocampal pathology and
      related behavioral deficits. Compared to IL-2 wild-type (WT) mice, IL-2 KO mice
      have a marked and selective loss of septal cholinergic neurons that occurs
      between the third postnatal week and adulthood. Given that the development of
      septal neurons is completed by embryonic day 17 and that IL-2 KO mice exhibit
      peripheral autoimmunity that develops progressively post-weaning, our data and
      others led us to postulate that the loss of septal neurons in adult IL-2 KO mice
      is due to selective autoimmune neurodegeneration that coincides with increasing
      levels of peripheral autoimmunity. Thus, the present study tested the hypotheses:
      (1) that T cells selectively target the septum, and; (2) that T lymphocyte
      infiltration to the septum would correlate with peripheral autoimmune disease. We
      quantified CD3(+) T cells in the septum, hippocampus, and cerebellum of IL-2 KO
      and IL-2 WT mice at ages ranging from 2 to 14 weeks. T cells infiltrated the
      brains of IL-2 deficient mice, but were not selective for the septum. Brain T
      lymphocyte levels in IL-2 KO mice correlated positively with the degree of
      peripheral autoimmunity. We did not detect CD19(+) B lymphocytes, IgG-positive
      lymphocytes or IgG deposition indicative of autoantibodies in the brains of IL-2
      KO mice. Further study is needed to understand how IL-2 deficiency-induced
      autoimmune T lymphocytes interact with endogenous brain cells to alter function
      and promote disease.

PMID- 19595745
TI  - Modulation of thioredoxin reductase-2 expression in EAhy926 cells: implications
      for endothelial selenoprotein hierarchy.
AB  - BACKGROUND: We examined the expression of the mitochondrial selenoenzyme TrxR2 in
      the endothelial cell line EAhy926 under conditions known to modify its
      cytoplasmic counterpart TrxR1. METHODS: Cells were cultured with varying
      concentrations of selenite, sulforaphane or the Ca2+ ionophore A23187 for 72-h,
      prior to assay of TrxR concentration and activity. Further cultures underwent
      prolonged (7-day) Se-depletion before selenoprotein measurement. RESULTS: In Se
      deficient cultures, neither Se, A23187 or sulforaphane affected TrxR2
      concentration, while these treatments induced TrxR1 concentration (p<0.05). When
      co-incubated, optimal concentrations of Se (40 nM) and sulforaphane (4 microM)
      only modestly increased TrxR2 protein (approximately 1.3-fold), compared with
      TrxR1 (approximately 4-fold). In Se-deficient cells, TrxR activity was unaffected
      by sulforaphane or A23187. Prolonged Se-depletion caused a comparatively small
      reduction in TrxR2 (66% TrxR2 retained) against TrxR1 and glutathione peroxidase
      1 activity (38% and 17% retained, respectively). CONCLUSIONS: The relative
      resistance of TrxR2 to Se-deprivation and induction by sulforaphane and A23187
      suggests TrxR2 lies near the top of the selenoprotein hierarchy in EAhy926 cells
      and exhibits near maximum expression under a range of culture conditions. In Se
      deficiency an inactive (possibly truncated) TrxR1 is produced in response to
      stimulus by sulforaphane and A23187. GENERAL SIGNIFICANCE: These observations
      underpin a likely critical antioxidant role for TrxR2 and TrxR1 in the
      endothelium.

PMID- 19595744
TI  - Role for GABA agonists in the nucleus accumbens in regulating morphine self
      administration.
AB  - In the present study, functional roles of GABA receptors in the nucleus accumbens
      on morphine self-administration behavior were investigated. Male Sprague-Dawley
      rats were trained to press lever for morphine (0.1 mg/kg per infusion) during
      daily 1-h self-administration session. After establishing stable baseline
      responses, rats were given microinjections of the GABA(A) receptor agonist
      muscimol (0, 250 and 500 ng/microl, bilateral) or the GABA(B) receptor agonist
      baclofen (0, 100 and 250 ng/microl, bilateral) into the nucleus accumbens
      immediately before the morphine self-administration. Microinjection of muscimol
      (250 and 500 ng/microl) into the nucleus accumbens, but not baclofen, decreased
      morphine self-administration responses. These results suggest that activation of
      GABA(A) receptors, but not GABA(B) receptors, in the nucleus accumbens plays a
      critical role in modulating the reinforcing effects of morphine.

PMID- 19595747
TI  - The phylogeny of orthoretroviral long terminal repeats (LTRs).
AB  - LTRs are sequence elements in retroviruses and retrotransposons which are
      difficult to align due to their variability. One way of handling such cases is to
      use Hidden Markov Models (HMMs). In this work HMMs of LTRs were constructed for
      three groups of orthoretroviruses: the betaretroviruslike human MMTV-like (HML)
      endogenous retroviruses, the lentiviruses, including HIV, and gammaretroviruslike
      human endogenous retroviruses (HERVs). The HMM-generated LTR alignments and the
      phylogenetic trees constructed from them were compared with trees based on
      alignments of the pol gene at the nucleic acid level. The majority of branches in
      the LTR and pol based trees had the same order for the three retroviral genera,
      showing that HMM methods are successful in aligning and constructing phylogenies
      of LTRs. The HML LTR tree deviated somewhat from the pol tree for the groups
      HML3, HML7 and HML6. Among the gammaretroviruslike proviruses, the exogenous
      Mouse Leukemia Virus (MLV) was highly related to HERV-T in the pol based tree,
      but not in the LTR based tree. Aside from these differences, the similarity
      between the trees indicates that LTRs and pol coevolved in a largely monophyletic
      way.

PMID- 19595746
TI  - Oligomerization of Bacillus subtilis DesR is required for fine tuning regulation
      of membrane fluidity.
AB  - BACKGROUND: The DesK-DesR two-component system regulates the order of membrane
      lipids in the bacterium Bacillus subtilis by controlling the expression of the
      des gene coding for the delta 5-acyl-lipid desaturase. To activate des
      transcription, the membrane-bound histidine kinase DesK phosphorylates the
      response regulator DesR. This covalent modification of the regulatory domain of
      dimeric DesR promotes, in a cooperative fashion, the hierarchical occupation of
      two adjacent, non-identical, DesR-P binding sites, so that there is a shift in
      the equilibrium toward the tetrameric active form of the response regulator.
      However, the mechanism of regulation of DesR activity by phosphorylation and
      oligomerization is not well understood. METHODS: We employed deletion analysis
      and reporter fusions to study the role of the N-terminal domain on DesR activity.
      In addition, electromobility shift assays were used to analyze the binding
      capacity of the transcription factor to deletion mutants of the des promoter.
      RESULTS: We show that DesR lacking the N-terminal domain is still able to bind to
      the des promoter. We also demonstrate that if the RA site is moved closer to the 
      35 region of Pdes, the adjacent site RB is dispensable for activation. GENERAL
      SIGNIFICANCE: Our results indicate that the unphosphorylated regulatory domain of
      DesR obstructs the access of the recognition helix of DesR to its DNA target. In
      addition, we present evidence showing that RB is physiologically relevant to
      control the activation of the des gene when the levels of DesR-P reach a critical
      threshold.

PMID- 19595748
TI  - Induction of CYP1A1, 2B, 2E1 and 3A in rat liver by organochlorine pesticide
      dicofol.
AB  - The present study has determined the ability of dicofol, an organochlorine
      pesticide, to induce cytochrome P450 using rats treated with 1, 10, and 25mg/kg
      dicofol intraperitoneally for 4 days. Treatments with 10 and 25mg/kg dicofol
      produced dose-related increases of cytochrome P450 and cytochrome b(5) contents
      and NADPH-cytochrome c reductase, 7-ethoxyresorufin O-deethylase,
      pentoxyresorufin O-dealkylase, aniline hydroxylase, and erythromycin N
      demethylase activities in liver microsomes. The treatments also increased
      glutathione S-transferase and superoxide dismutase activities in liver cytosol.
      Dicofol at 1mg/kg produced a general trend towards increases of the
      aforementioned enzyme levels. The results of immunoblot analyses showed that 10
      and 25mg/kg dicofol increased protein levels of CYP1A1, CYP2B, CYP2E1, and 3A in
      liver. RT-PCR data indicated that dicofol induced mRNA expression of liver
      CYP1A1, CYP2B, and CYP3A. Pretreatments of rats with 10 and 25mg/kg dicofol
      decreased phenobarbital-induced sleeping time by 34% and 39%, respectively.
      Dicofol pretreatment at 25mg/kg increased CCl4-induced serum alanine
      aminotransferase activity by 4.3-fold and aspartate aminotransferase activity by
      4.1-fold. The present study demonstrates that dicofol has the ability to induce
      CYP1A1, CYP2B, CYP2E1, and CYP3A in the liver and increase phenobarbital
      metabolism and CCl4 toxicity in rats.

PMID- 19595749
TI  - Effect of ETBE on reproductive steroids in male rats and rat Leydig cell
      cultures.
AB  - These experiments were conducted to follow up on a report of testis seminiferous
      tubular degeneration in Fischer 344 rats treated with high doses of ethyl t-butyl
      ether (ETBE). Also, high doses of a related compound, methyl t-butyl ether
      (MTBE), had been shown to reduce circulating testosterone (T) in rats. Isolated
      rat Leydig cells were used to compare hCG-stimulated T production following
      exposure to ETBE, MTBE, and their common main metabolite, TBA. In addition, male
      Fischer 344 rats were gavaged daily with 600 mg/kg, 1200 mg/kg or 1800 mg/kg ETBE
      in corn oil (n=12) for 14 days, the 1200 mg/kg dose chosen for comparison with a
      prior 14-day MTBE gavage experiment. In cell culture experiments, TBA was more
      potent than either ETBE or MTBE, both of which caused similar inhibition of T
      production at equimolar concentrations. In the in vivo study, no significant
      plasma T reduction was seen 1h after the final 1200 mg/kg ETBE dose, whereas 1200
      mg/kg MTBE had significantly lowered T when administered similarly to Sprague
      Dawley rats. Some rats treated with 1800 mg/kg ETBE had noticeably lower T
      levels, and the group average T level was 66% of corn oil vehicle control
      (p>0.05) with high variability also evident in ETBE-treated rats. 17beta
      Estradiol had been increased by 1200 mg/kg MTBE, and was elevated in the 1200 and
      1800 mg/kg ETBE dose groups (p<0.05), both groups also experiencing significantly
      reduced body weight gain. None of these effects were seen with 600 mg/kg/day
      ETBE. No definitive evidence of androgen insufficiency was seen in accessory
      organ weights, and no testicular pathology was observed after 14 days in a small
      subset of 1800 mg/kg ETBE-treated animals. Like MTBE, ETBE appears to be capable
      of altering reproductive steroid levels in peripheral blood sampled 1h after
      treatment, but only with extremely high doses that inhibit body weight gain and
      may produce mortality.

PMID- 19595751
TI  - Genotoxicity of sodium arsenite and DNA fragmentation in ovarian cells of rat.
AB  - Present study examined the genotoxic effects of arsenite in ovarian tissue of rat
      at 56 days of age. Immature (28 days old) female rats were exposed to different
      doses (50, 100, and 200 ppm) of sodium arsenite in drinking water for 28 days.
      DNA damage in ovarian tissue was measured by comet assay. All doses induced
      significant decrease in ovarian weight in a dose-dependent manner compared to
      control, more prominently at (P<0.001) 100 and 200 ppm. All the comet assay
      parameters showed significant difference with arsenite treatment compared to
      control group. In treatment groups, mean number of cells with intact DNA
      decreased while, mean comet number increased (P<0.001) in a dose-dependent manner
      compared to control. Significant decrease (P<0.05) was observed in mean comet
      length, height, comet head diameter and %DNA in comet head of high dose groups
      compared to control group. Dose dependent increase was found in mean comet tail
      length, %DNA in tail, tail moment and olive tail moment in high dose groups
      compared to control group. The study indicates that arsenic caused DNA damage to
      ovarian cells particularly at high doses and ensure comet assay as an effective
      method to detect DNA damage in tissue caused by metals.

PMID- 19595750
TI  - Pipping success and liver mRNA expression in chicken embryos exposed in ovo to C8
      and C11 perfluorinated carboxylic acids and C10 perfluorinated sulfonate.
AB  - Several perfluoroalkyl compounds (PFCs) are ubiquitous environmental contaminants
      that can biomagnify in species at high trophic levels including wild birds.
      Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have been
      detected in wild birds and are known to reduce hatching success of laboratory
      exposed chicken embryos at environmentally relevant concentrations. Limited
      toxicity data are available regarding avian exposure to PFCs of chain lengths
      greater than C(8), which are of increasing environmental relevance following the
      recent phase-out of PFOS and PFOA. In this study, linear PFOA,
      perfluoroundecanoic acid (PFUdA) and perfluorodecane sulfonate (PFDS) were
      injected into the air cell of white leghorn chicken eggs (Gallus gallus
      domesticus) prior to incubation to determine effects on embryo pipping success.
      Furthermore, mRNA expression of key genes involved in pathways implicated in PFC
      toxicity was monitored in liver tissue. PFOA, PFUdA or PFDS had no effect on
      embryonic pipping success at concentrations up to 10 microg/g. All PFCs
      accumulated in the liver to concentrations greater than the initial whole-egg
      concentration as determined by HPLC/MS/MS. Hepatic accumulation was highest for
      PFOA (4.5 times) compared to PFUdA and PFDS. Cytochrome P450 1A4 and liver fatty
      acid binding protein mRNA expression increased after exposure to PFUdA but was
      only statistically significant at 10 microg/g; several orders of magnitude higher
      than levels found in wild bird eggs. Based on the present results for white
      leghorn chickens, current environmental concentrations of PFOA, PFUdA and PFDS
      are unlikely to affect the hatching success of wild birds.

PMID- 19595752
TI  - Cytotoxic, mutagenic and genotoxic effects of new anti-T. cruzi 5
      phenylethenylbenzofuroxans. Contribution of phase I metabolites on the
      mutagenicity induction.
AB  - 5-Phenylethenylbenzofuroxans have displayed in vitro and in vivo activity against
      Trypanosoma cruzi, the etiologic agent of American Trypanosomiasis. On the basis
      of benzofuroxans pre-clinical studies we evaluated the potential of six 5
      phenylethenyl derivatives to induce cytotoxicity, mutagenicity and genotoxicity
      using different in vitro models. Cytotoxic effects were evaluated using a set of
      cells, mammal pre-monocytic macrophages, V-79 lung fibroblast from Chinese
      hamster, and colorectal adenocarcinoma Caco-2 cells, in the MTT viability assay.
      Mutagenicity was tested in the Ames assay using Salmonella typhimurium TA98
      strain with and without metabolic activation by S9-rat liver homogenate. The
      genotoxic potentials were evaluated with the alkaline single cell gel
      electrophoresis (comet assay) in V-79 cells. In view of the Ames test results we
      study whether the main mammals' phase I metabolites, the corresponding o
      nitroanilines, are involved in the mechanism of mutagenicity. These metabolites
      are produced by NADPH-dependent enzymes in cytosol and by xanthine oxidase and
      cytochrome P450 in microsomes from rat liver. Among them, the electronic property
      of phenyl substituent seems to be responsible for this effect. It could be
      pointed out that the equimolecular mixture of compounds 1 and 2 (5E- and 5Z-(2
      phenylethenyl)benzofuroxan, respectively) could be used in further clinical
      studies as anti-T. cruzi drug.

PMID- 19595753
TI  - Concurrent-vowel and tone recognition by Mandarin-speaking cochlear implant
      users.
AB  - In Mandarin Chinese, tonal patterns are lexically meaningful. In a multi-talker
      environment, competing tones may create interference in addition to competing
      vowels and consonants. The present study measured Mandarin-speaking cochlear
      implant (CI) users' ability to recognize concurrent vowels, tones, and syllables
      in a concurrent-syllable recognition test. Concurrent syllables were constructed
      by summing either one Chinese syllable each from one male and one female talker
      or two syllables from the same male talker. Each talker produced 16 different
      syllables (4 vowels combined with 4 tones); all syllables were normalized to have
      the same overall duration and amplitude. Both single- and concurrent-syllable
      recognition were measured in 4 adolescent and 4 adult CI subjects, using their
      clinically assigned speech processors. The results showed no significant
      difference in performance between the adolescent and adult CI subjects. With
      single syllables, mean vowel recognition was 90% correct, while tone and syllable
      recognition were only 63% and 57% correct, respectively. With concurrent
      syllables, vowel, tone, and syllable recognition scores dropped by 40-60
      percentage points. Concurrent-syllable performance was significantly correlated
      with single-syllable performance. Concurrent-vowel and syllable recognition were
      not significantly different between the same- and different-talker conditions,
      while concurrent-tone recognition was significantly better with the same-talker
      condition. Vowel and tone recognition were better when concurrent syllables
      contained the same vowels or tones, respectively. Across the different vowel
      pairs, tone recognition was less variable than vowel recognition; across the
      different tone pairs, vowel recognition was less variable than tone recognition.
      The present results suggest that interference between concurrent tones may
      contribute to Mandarin-speaking CI users' susceptibility to competing-talker
      backgrounds.

PMID- 19595754
TI  - Visual influences on ferret auditory cortex.
AB  - Multisensory neurons are now known to be widespread in low-level regions of the
      cortex usually thought of as being responsible for modality-specific processing.
      The auditory cortex provides a particularly striking example of this, exhibiting
      responses to both visual and somatosensory stimulation. Single-neuron recording
      studies in ferrets have shown that each of auditory fields that have been
      characterized using physiological and anatomical criteria also receives visual
      inputs, with the incidence of visually-sensitive neurons ranging from 15% to 20%
      in the primary areas to around 50% or more in higher-level areas. Although some
      neurons exhibit spiking responses to visual stimulation, these inputs often have
      subthreshold influences that modulate the responses of the cortical neurons to
      sound. Insights into the possible role played by the visual inputs can be
      obtained by examining their sources of origin and the way in which they alter the
      processing capabilities of neurons in the auditory cortex. These studies suggest
      that one of the functions of the visual input to auditory cortex is to sharpen
      the relatively imprecise spatial coding typically found there. Because the extent
      to which this happens varies between cortical fields, the investigation of
      multisensory interactions can also help in understanding their relative
      contributions to auditory perception.

PMID- 19595755
TI  - Neuronal mechanisms, response dynamics and perceptual functions of multisensory
      interactions in auditory cortex.
AB  - Most auditory events in nature are accompanied by non-auditory signals, such as a
      view of the speaker's face during face-to-face communication or the vibration of
      a string during a musical performance. While it is known that accompanying visual
      and somatosensory signals can benefit auditory perception, often by making the
      sound seem louder, the specific neural bases for sensory amplification are still
      debated. In this review, we want to deal with what we regard as confusion on two
      topics that are crucial to our understanding of multisensory integration
      mechanisms in auditory cortex: (1) Anatomical Underpinnings (e.g., what circuits
      underlie multisensory convergence), and (2) Temporal Dynamics (e.g., what time
      windows of integration are physiologically feasible). The combined evidence on
      multisensory structure and function in auditory cortex advances the emerging view
      of the relationship between perception and low level multisensory integration. In
      fact, it seems that the question is no longer whether low level, putatively
      unisensory cortex is accessible to multisensory influences, but how.

PMID- 19595756
TI  - Age-related increase of prostaglandin D(2) synthase concentration and glycation
      in ovine cerebrospinal fluid.
AB  - Prostaglandin D(2) synthase (PGDS) is a glycoprotein that is exclusively brain
      derived and is one of the most abundant proteins in the cerebrospinal fluid
      (CSF). Due to its high CSF specificity, it can be used as a tool for the
      diagnosis of central nervous system (CNS) disorders. However, several studies
      have yielded contradictory CSF PGDS concentrations in various CNS
      neurodegenerative disorders. Sheep CSF samples from different ages were used in
      this study and 2-dimensional electrophoresis (2-DE) was applied in PGDS
      identification and concentration calculation. SYPRO Ruby Protein Gel Stain was
      the staining method used to stain the 2-DE gel protein spots. Pro-Q Emerald 488
      Staining for Glycoproteins was used for the staining of glycoproteins. A total of
      nine PGDS isoforms were identified and CSF total PGDS concentration was
      calculated to increase linearly by 44% from young (0.9323+/-0.0637mgdL(-1)) to
      old (1.3669+/-0.0558mgdL(-1)). However, the proportion of CSF total PGDS as a
      percentage of CSF total protein was discovered to decrease exponentially with
      age. This was due to the influence of larger age-related increase in CSF albumin
      concentration (>200% from young to old) as albumin is the most abundant protein
      in the CSF (>60% of total CSF proteins). Active deglycosylation was not observed
      in PGDS isoforms during healthy ageing. Some PGDS isoforms were observed to have
      age-related increase in glycation. These findings suggest that CSF PGDS
      concentration is increased during healthy ageing and must be taken into
      consideration when using PGDS as a potential biomarker in diagnosing CNS
      neurodegenerative disorders. Whether age-related increase in the glycation of
      some CSF PGDS isoforms will result in detrimental effects on the PGDS protein
      function needs further investigations.

PMID- 19595757
TI  - Genotoxicity testing in vitro - development of a higher throughput analysis
      method based on the comet assay.
AB  - Higher throughput methods, high content analysis and automated screening methods
      are of highest demand in drug development today. In toxicology, these strategies
      are becoming increasingly important, as well. Therefore, an integrated higher
      throughput method for the comet assay is addressed by the development presented
      here. The sensitivity, specificity and relevance of the comet assay as a method
      for determination of DNA damage in vivo and in vitro have been highlighted in
      many studies. Actually, efforts are made to include it in a panel of genotoxicity
      tests for regulatory purposes. However, the standard comet assay is a time
      consuming procedure due to the specific methods needed. The improvements
      presented here lead to a faster and easier slide-production, a smaller amount of
      cells needed, a higher amount of comets quantified, a fully automated analysis of
      comets including reanalysis, storing, visualisation and documentation
      possibilities using standard comet quantification models such as tail length or
      tail moment, and - by introduction of clearly definable selection criteria based
      on image analysis algorithms - clearly improve objectivity and standardization of
      the analysis procedure. Results prove the high reproducibility, flexibility,
      efficiency and suitability of the procedure as a fully automated analysis method
      in higher throughput genotoxicity testing in vitro.

PMID- 19595758
TI  - Study of cytotoxic effect of photodynamically and sonodynamically activated
      sensitizers in vitro.
AB  - High resolution imaging of biological structures and their changes induced by
      different agents such as drugs are commonly performed by confocal and electron
      microscopy. The past decade has witnessed an emersion of the atomic force
      microscopy (AFM) from solid-state physics into cell biology and even medical
      applications. For these reasons, we used this relatively new microscopic
      technique to study the morphology of cell lines. We imaged the cells by atomic
      force microscopy before and after the photodynamic therapy (PDT) using the
      photosensitizer ClAlPcS(2). We also compared the impact of the photosensitizer in
      combination with silymarin antioxidant on cancer and non-cancer cell lines by
      measuring the kinetic production of reactive oxygen species (ROS). PDT was
      induced by LED source with total irradiation dose of 15 J cm(-2) and SDT was
      induced by therapeutic ultrasound with frequency of 1 MHz, intensity 2 W cm(-2)
      and time of exposition 10 min. The results show ROS kinetic production within the
      cells during PDT, sonodynamic therapy (SDT) and modification of morphological
      features investigated by AFM. The combination of a sensitizer and the specific
      light source can lead to the loss of surface rigidity and eventually to dramatic
      changes of the cell shape, which we can study by AFM.

PMID- 19595759
TI  - Diazinon oxon interferes with differentiation of rat C6 glioma cells.
AB  - The purpose of this study was to evaluate the toxicity of diazinon oxon (DZO), a
      major in vivo metabolite of the organophosphate insecticide diazinon (DZ), on
      differentiating rat C6 glioma cells. At concentrations shown to be non-cytotoxic
      by both the MTT and the Kenacid blue dye binding assays (1, 5 and 10 microM), DZO
      caused after 24h a reduction in the number of extensions developed from C6 cells
      induced to differentiate by serum withdrawal and addition of sodium butyrate.
      Densitometric scanning of Western blots of extracts of C6 cells demonstrated
      that, at all concentrations used, DZO decreased after 24h the expression of glial
      fibrillary acidic protein (GFAP) compared to controls. In addition, exposure to
      10 microM DZO for 24h reduced the levels of tubulin and microtubule associated
      protein 1B (MAP1B). On the other hand, levels of MAP2c were not affected by DZO
      treatment. In contrast to our previous data on DZ, the above findings suggest
      that its oxon metabolite, DZO, may, at biologically relevant, subcytotoxic
      concentrations, interfere with glial cell differentiation.

PMID- 19595760
TI  - Interpreting epidemiologic studies of developmental neurotoxicity: conceptual and
      analytic issues.
AB  - This paper discusses issues pertaining to the validity, precision, and
      interpretation of epidemiologic studies of neurotoxicity. With regard to
      validity, the critical issues pertain to the appropriate strategy for confounder
      adjustment, particularly when confounders are complex, multi-faceted constructs,
      and to the need for greater clarity and transparency in articulating the causal
      relationships implicit in the analytic approach applied. With regard to
      precision, the critical issue is a need to identify the contributors to the
      substantial variability observed in the effect estimates that describe dose
      response and dose-effect relationships. In addition to methodological sources,
      such as imprecision in estimating dose at the critical organ site(s), true inter
      individual differences in susceptibility to a neurotoxicant could also contribute
      to the variability. Variability might be reduced by taking full account of
      factors such as co-exposures or health co-morbidities, genetic polymorphisms, and
      the social ecology of exposure. With regard to interpretation, we need to do a
      better job as a field conveying to risk assessors and others the ecological
      significance of the types of performance deficits observed following
      neurotoxicant exposure, emphasizing the distinction between individual and
      population risk. A final issue discussed is the need to define standards for the
      conduct, analysis, and reporting of epidemiologic studies of neurotoxicity,
      similar to those developed for other fields.

PMID- 19595761
TI  - The C-terminus of Raf-1 acts as a 14-3-3-dependent activation switch.
AB  - The Raf-1 protein kinase is a major activator of the ERK MAPK pathway, which
      links signaling by a variety of cell surface receptors to the regulation of cell
      proliferation, survival, differentiation and migration. Signaling by Raf-1 is
      regulated by a complex and poorly understood interplay between phosphorylation
      events and protein-protein interactions. One important mode of Raf-1 regulation
      involves the phosphorylation-dependent binding of 14-3-3 proteins. Here, we have
      examined the mechanism whereby the C-terminal 14-3-3 binding site of Raf-1, S621,
      controls the activation of MEK-ERK signaling. We show that phosphorylation of
      S621 turns over rapidly and is enriched in the activated pool of endogenous Raf
      1. The phosphorylation on this site can be mediated by Raf-1 itself but also by
      other kinase(s). Mutations that prevent the binding of 14-3-3 proteins to S621
      render Raf-1 inactive by specifically disrupting its capacity to bind to ATP, and
      not by gross conformational alteration as indicated by intact MEK binding.
      Phosphorylation of S621 correlates with the inhibition of Raf-1 catalytic
      activity in vitro, but 14-3-3 proteins can completely reverse this inhibition.
      Our findings suggest that 14-3-3 proteins function as critical cofactors in Raf-1
      activation, which induce and maintain the protein in a state that is competent
      for both ATP binding and MEK phosphorylation.

PMID- 19595763
TI  - A novel mutation (F71L) in alphaA-crystallin with defective chaperone-like
      function associated with age-related cataract.
AB  - Age-related cataract (ARC) is a multifactorial disease and the leading cause of
      blindness worldwide. Genetic predisposition in association with other etiological
      factors may contribute to ARC. However, gene mutation studies on ARC are scanty.
      In the present work, we identified a genetic variation (F71L) in the exon-2 of
      CRYAA (alphaA-crystallin) gene in three unrelated female sporadic cases among 711
      ARC patients but not in 265 normal non-cataractous controls by SSCP and RFLP
      analysis. By comparing human recombinant wild-type and F71L-alphaA-crystallin, we
      characterized the functional significance of this missense mutation.
      Chromatography, fluorescence and far- and near-UV CD studies indicated that F71L
      missense mutation did not significantly affect the apparent molecular mass,
      secondary and tertiary structures and hydrophobicity of alphaA-crystallin. While
      the mutant alphaA-crystallin displayed significant (35-90%) loss of chaperone
      like activity (CLA) in thermal aggregation of carbonic anhydrase, betaL- and
      gamma-crystallins, it showed moderate (10-50%) loss in CLA in DTT-induced
      aggregation of insulin and lysozyme. This is the first report of an alphaA-F71L
      mutation being associated with ARC and suggests that ARC in individuals carrying
      this mutation (F71L) might be due to the overall loss of in vivo chaperone
      activity due to interaction with other environmental factors.

PMID- 19595762
TI  - Tickled PINK1: mitochondrial homeostasis and autophagy in recessive Parkinsonism.
AB  - Dysregulation of mitochondrial structure and function has emerged as a central
      factor in the pathogenesis of Parkinson's disease and related parkinsonian
      disorders (PD). Toxic and environmental injuries and risk factors perturb
      mitochondrial complex I function, and gene products linked to familial PD often
      affect mitochondrial biology. Autosomal recessive mutations in PTEN-induced
      kinase 1 (PINK1) cause an L-DOPA responsive parkinsonian syndrome, stimulating
      extensive interest in the normal neuroprotective and mitoprotective functions of
      PINK1. Recent data from mammalian and invertebrate model systems converge upon
      interactions between PINK1 and parkin, as well as DJ-1, alpha-synuclein and
      leucine rich repeat kinase 2 (LRRK2). While all studies to date support a
      neuroprotective role for wild type, but not mutant PINK1, there is less agreement
      on subcellular compartmentalization of PINK1 kinase function and whether PINK1
      promotes mitochondrial fission or fusion. These controversies are reviewed in the
      context of the dynamic mitochondrial lifecycle, in which mitochondrial structure
      and function are continuously modulated not only by the fission-fusion machinery,
      but also by regulation of biogenesis, axonal/dendritic transport and autophagy. A
      working model is proposed, in which PINK1 loss-of-function results in
      mitochondrial reactive oxygen species (ROS), cristae/respiratory dysfunction and
      destabilization of calcium homeostasis, which trigger compensatory fission,
      autophagy and biosynthetic repair pathways that dramatically alter mitochondrial
      structure. Concurrent strategies to identify pathways that mediate normal PINK1
      function and to identify factors that facilitate appropriate compensatory
      responses to its loss are both needed to halt the aging-related penetrance and
      incidence of familial and sporadic PD.

PMID- 19595764
TI  - Retinoic acid regulates anterior-posterior patterning within the lateral plate
      mesoderm of Xenopus.
AB  - The lateral plate mesoderm (LPM) lines the body cavities, gives rise to the heart
      and circulatory system and is responsible for patterning the underlying endoderm.
      We describe gene expression domains within the lateral plate mesoderm of the
      neurula stage Xenopus embryo that demonstrate a marked anterior posterior pattern
      in that tissue. FoxF1 and Nkx-2.5 are expressed in the anterior LPM, Hand1 in the
      middle and Xsal-1 in the posterior LPM. Since retinoic acid is known to pattern
      many tissues during development, and RALDH2, the enzyme primarily responsible for
      retinoic acid synthesis, is expressed in the anterior and dorsal LPM, we
      hypothesized that retinoic acid is necessary for correct patterning of the LPM.
      Exposure to exogenous retinoic acid during neurulation led to an expansion of the
      anterior and middle expression domains and a reduction of the posterior domain
      whereas exposure to a retinoic acid antagonist resulted in smaller anterior and
      middle expression domains. Furthermore, inhibition of RALDH2, which should
      decrease endogenous RA levels, caused a reduction of anterior domains indicating
      that endogenous RA is necessary for regulating their size. After altering
      retinoic acid signaling in a temporally restricted window, the displaced anterior
      posterior pattern is maintained until gut looping, as demonstrated by permanently
      altered Hand1, FoxF1, xHoxC-10, and Pitx2 expression domains. We conclude that
      the broad expression domains of key transcription factors demonstrate a novel
      anterior-posterior pattern within the LPM and that retinoic acid can regulate the
      size of these domains in a coordinated manner.

PMID- 19595766
TI  - Identification and characterization of two arginine kinases from the parasitic
      insect Ctenocephalides felis.
AB  - Arginine kinase (ATP:l-arginine omega-N-phosphotransferase, EC2.7.3.3.; AK) is an
      enzyme crucial for the energy metabolism of insects and other invertebrates, that
      has known allergenic potential in humans and that has been proposed as a
      pesticidal drug target. Here we report the identification, cDNA cloning, genomic
      gene structure and functional expression of AK genes from Ctenocephalides (C.)
      felis (cat flea). In contrast to other insect species investigated so far, C.
      felis possesses two AK genes, cfak1 and cfak2, encoding the functional enzymes
      CfAK1 and CfAK2 that can be distinguished by their guanidino substrate
      specificity and the kinetic parameters for their natural substrates. Molecular
      modelling on CfAK1 and CfAK2 based on the Limulus polyphemus AK X-ray structure
      (Zhou et al., 1998) and substrate docking studies provide a potential rational
      for the observed specificities. Evidence is provided that adult fleas express
      predominantly CfAK1 as an abundant soluble protein, and that in vivo in C. felis,
      the AK metabolites are present in concentration ranges relevant for this enzyme.

PMID- 19595765
TI  - Notch-responsive cells initiate the secondary transition in larval zebrafish
      pancreas.
AB  - Zebrafish provide a highly versatile model in which to study vertebrate
      development. Many recent studies have elucidated early events in the
      organogenesis of the zebrafish pancreas; however, several aspects of early
      endocrine pancreas formation in the zebrafish are not homologous to the mammalian
      system. To better identify mechanisms of islet formation in the zebrafish, with
      true homology to those observed in mammals, we have temporally and spatially
      characterized zebrafish secondary islet formation. As is the case in the mouse,
      we show that Notch inhibition leads to precocious differentiation of endocrine
      tissues. Furthermore, we have used transgenic fish expressing fluorescent markers
      under the control of a Notch-responsive element to observe the precursors of
      these induced endocrine cells. These pancreatic Notch-responsive cells represent
      a novel population of putative progenitors that are associated with larval
      pancreatic ductal epithelium, suggesting functional homology between secondary
      islet formation in zebrafish and the secondary transition in mammals. We also
      show that Notch-responsive cells persist in the adult pancreas and possess the
      classical characteristics of centroacinar cells, a cell type believed to be a
      multipotent progenitor cell in adult mammalian pancreas.

PMID- 19595767
TI  - Interactions between neuroactive steroids and reelin haploinsufficiency in
      Purkinje cell survival.
AB  - We determined total Purkinje cell (PC) numbers in cerebella of wild-type (+/+)
      and heterozygous (rl/+) reeler mice of either sex during early postnatal
      development; in parallel, we quantified levels of neuroactive steroids in the
      cerebellum with mass spectrometry. We also quantified reelin mRNA and protein
      expression with RT-PCR and Western blotting. PC numbers are selectively reduced
      at postnatal day 15 (P15) in rl/+ males in comparison to +/+ males, +/+ females,
      and rl/+ females. Administration of 17beta-estradiol (17beta-E) into the cisterna
      magna at P5 increases PC numbers in rl/+ males, but not in the other groups;
      conversely, estrogen antagonists 4-OH-tamoxifen or ICI 182,780 reduce PC numbers
      in +/+ and rl/+ females, but have no effect in males. Testosterone (T) levels at
      P5 are much higher in males than in females, reflecting the perinatal
      testosterone surge in males. In addition, rl/+ male cerebella at P5 show a
      peculiar hormonal profile in comparison with the other groups, consisting of
      increased levels of T and 17beta-E, and decreased levels of dihydrotestosterone.
      RT-PCR analysis indicated that heterozygosity leads to a 50% reduction of reelin
      mRNA in the cerebellum in both sexes, as expected, and that 17beta-E upregulates
      reelin mRNA, particularly in rl/+ males; reelin mRNA upregulation is associated
      with an increase of all major reelin isoforms. These effects may represent a
      novel model of how reelin deficiency interacts with variable perinatal levels of
      neuroactive steroids, leading to gender-dependent differences in genetic
      vulnerability.

PMID- 19595768
TI  - Chronic rotenone exposure reproduces Parkinson's disease gastrointestinal
      neuropathology.
AB  - Gastrointestinal disorders, particularly severe constipation and delayed gastric
      emptying, are core symptoms of Parkinson's disease that affect most patients.
      However, the neuropathological substrate and physiological basis for this
      dysfunction are poorly defined. To begin to explore these phenomena in laboratory
      models of PD, rats were treated with either vehicle or rotenone (2.0 mg/kg, i.p.;
      5 days/week) for 6-weeks. Myenteric plexus alpha-synuclein aggregate pathology
      and neuron loss were assessed 3-days and 6-months after the last rotenone
      injection. Gastrointestinal motility was assessed at 3-days, 1-month and 6-months
      after the last rotenone injection. Rotenone treatment caused an acute reduction
      in alpha-synuclein-immunoreactivity, but this was followed 6 months later by a
      robust increase in aggregate pathology and cytoplasmic inclusions that were
      similar in appearance to enteric Lewy-bodies in idiopathic PD. Rotenone-treated
      rats also had a moderate but permanent loss of small intestine myenteric neurons
      and an associated modest slowing of gastrointestinal motility 6-months after
      treatment. Our results suggest that a circumscribed exposure to an environmental
      toxicant can cause the delayed appearance of parkinsonian alpha-synuclein
      pathology in the enteric nervous system and an associated functional deficit in
      gastrointestinal motility. The rotenone model may therefore, provide a means to
      investigate pathogenic mechanisms and to test new therapeutic interventions into
      gastrointestinal dysfunction in PD.

PMID- 19595769
TI  - VDAC and ERalpha interaction in caveolae from human cortex is altered in
      Alzheimer's disease.
AB  - Voltage-dependent anion channel (VDAC) is a mitochondrial porin also found in the
      neuronal membrane (pl-VDAC), where its function may be related to redox
      homeostasis and apoptosis. Murine models have evidenced pl-VDAC into caveolae in
      a complex with estrogen receptor alpha (mERalpha), which participates in
      neuroprotection against amyloid beta (Abeta), and whose integration into this
      hydrophobic domain remains unclear. Here, we have demonstrated in caveolae of
      human cortex and hippocampus the presence of pl-VDAC and mERalpha, in a complex
      with scaffolding caveolin-1 which likely provides mERalpha stability at the
      plasma membrane. In Alzheimer's disease (AD) brains, VDAC was accumulated in
      caveolae, and it was observed in dystrophic neurites of senile plaques, whereas
      ERalpha was expressed in astrocytes surrounding the plaques. Together with
      previous data in murine neurons demonstrating the participation of pl-VDAC in
      Abeta-induced neurotoxicity, these data suggest that the channel may be involved
      in membrane dysfunctioning observed in AD neuropathology.

PMID- 19595770
TI  - Production and characterization of long-acting recombinant human albumin-EPO
      fusion protein expressed in CHO cell.
AB  - A long-lasting recombinant human albumin-linker-erythropoietin (EPO) is a human
      albumin gene fused to the N-terminal of EPO with a (GGSGG)(n)-repeated linker
      inserted between albumin and EPO. Albumin-EPO fusion genes were co-transfected
      with the dhfr gene. Albumin-EPO fusion protein has three kinds of sub-types
      (IALE, AD2LE, AD1LE). Albumin-EPO fusion protein was quantified with human EPO
      ELISA. The in vitro efficacy of albumin-EPO fusion protein was estimated using F
      36E cell, and in vivo efficacy of albumin-EPO fusion protein was estimated using
      normocythemic mice (B6D2F1). We also determined the in vivo half-life in a
      Sprague-Dawley rat. A PLA program analysis result demonstrated that the albumin
      EPO fusion protein IALE is about 7.8-fold more potent than rHuEPO in increasing
      the hematocrit of normal mice.

PMID- 19595771
TI  - Ultrastructure of avian eggshell during resorption following egg fertilization.
AB  - For skeletal mineralization, the avian embryo mobilizes calcium from its calcitic
      eggshell. This occurs through dissolution of specific interior regions of the
      shell in a process that also weakens the shell to allow hatching. Here, we have
      examined eggshell ultrastructure during dissolution occurring between laying of a
      fertilized egg (with incubation) and hatching of the chick (Gallus gallus). We
      have focused on changes in shell mammillae where the majority of dissolution
      takes place. Using scanning electron microscopy, we describe differences in
      matrix-mineral structure and relationships not observed in unfertilized eggs
      (unresorbed eggshell). We document changes in the calcium reserve body - an
      essential sub-compartment of mammillae - consistent with it being an early,
      primary source of calcium essential for embryonic skeletal growth. Dissolution
      events occurring in the calcium reserve sac and in the base plate of the calcium
      reserve body, and similar changes in surrounding bulk mammillae structure, all
      correlate with advancing skeletal embryonic calcification. The changes in
      mammillae sub-structures can generally be characterized as mineral dissolutions
      revealing fine surface topographies on remaining mineral surfaces and the
      exposure of an extensive, intracrystalline (occluded) organic matrix network. We
      propose that this mineral-occluded network regulates how shell mineral is
      dissolved by providing dissolution channels facilitating calcium release for the
      embryonic skeleton.

PMID- 19595773
TI  - Localization of the syntactic mismatch negativity in the temporal cortex: an MEG
      study.
AB  - Recent auditory oddball studies using syntactic stimuli report a syntactic effect
      on the mismatch negativity (sMMN) around 100-200 ms. For morphosyntactic
      violations, this sMMN effect has been localized in the left superior temporal
      cortex. Independently, a recent visual sentence processing study introduced a
      "sensory hypothesis" which postulates that sensory cortices are sensitive to
      syntactic violations when these are overtly marked by closed-class morphemes, and
      thus contribute to early syntax-related effects in EEG and MEG. The present study
      aimed to test the sensory hypothesis in the auditory modality by localizing the
      neuronal sources of the sMMN to phrase structure violations. Using whole head
      magnetoencephalography, two-word utterances which were syntactically correct,
      uncommon or incorrect due to a word category violation were presented in an
      auditory oddball paradigm. In the sMMN time window (100-180 ms), incorrect
      phrases elicited strongest activation in the left Sylvian fissure (including the
      primary auditory cortex) and in the left superior temporal sulcus. Prior to this,
      a very early grammaticality effect (40-80 ms), focused in the left Sylvian
      fissure, was found. An additional grammaticality effect in a later time window
      (280-380 ms) was localized in the anterior part of the superior temporal gyrus,
      the planum polare. Processing of an uncommon phrase did not differ from
      processing a correct phrase in any of the time windows, indicating the genuinely
      syntactic nature of the sMMN effect. Our results are in line with previous
      studies localizing the sMMN to morphosyntactic violations and are furthermore
      compatible with the sensory hypothesis of closed-class morphology based syntactic
      processes.

PMID- 19595772
TI  - Similar and dissociable mechanisms for attention to internal versus external
      information.
AB  - We compared two attentional executive processes: updating, which involved
      attending to a perceptually present stimulus, and refreshing, which involved
      attending to a mentally active representation of a stimulus no longer
      perceptually present. In separate blocks, participants either replaced a word
      being held in working memory with a different word (update), or they thought back
      to a just previously seen word that was no longer perceptually present (refresh).
      Bilateral areas of frontal cortex, supplementary motor area, and parietal cortex
      were similarly active for both updating and refreshing, suggesting that a common
      network of areas is recruited to bring information to the current focus of
      attention. In a direct comparison of update and refresh, regions more active for
      update than refresh included regions primarily in right frontal cortex, as well
      as bilateral posterior visual processing regions. Regions more active for refresh
      than update included regions primarily in left dorsolateral frontal and left
      temporal cortex and bilateral inferior frontal cortex. These findings help
      account for the similarity in areas activated across different cognitive tasks
      and may help specify the particular executive processes engaged in more complex
      tasks.

PMID- 19595775
TI  - An fMRI study of syntactic layers: sentential and lexical aspects of embedding.
AB  - Sentences with embedding are more complex than sentences without embedding,
      because they contain more syntactic layers in their phrasal architecture. Until
      now, neuroimaging studies tested embedded sentences that also included syntactic
      movement. To explore which cortical areas are specifically involved in the
      processing of syntactic layers, we used embedded sentences that did not include
      syntactic movement. We compared sentences in which the verb was complemented with
      an embedded sentence (CP complement) to sentences with noun phrase (NP)
      complements. The comparison of sentences with and without embedding revealed
      activations in the left IFG, bilateral temporo-parietal cortices, bilateral MTG,
      and precuneus. We further examined the effect of embedding at the lexical level.
      For this, we tested whether verbs that can select CP complements, namely, whose
      lexical entry includes a CP option, are more complex than verbs that do not
      select CP complements, even when both verb types appeared in sentences without
      embedding. The comparison of verbs that can take CP complements with verbs that
      can take NP complements, when these verbs appeared with prepositional phrase
      complements, revealed activations in bilateral anterior MTG and precuneus,
      showing that embedding also affects processing at the lexical level. The results
      thus show that sentential embedding, even without syntactic movement, loads onto
      several cortical resources including the left IFG, indicating that the generation
      of syntactic layers is cognitively costly, and that embedding affects processing
      at both the sentence and the lexical levels.

PMID- 19595776
TI  - Higher-level salamander relationships and divergence dates inferred from complete
      mitochondrial genomes.
AB  - Phylogenetic relationships among the salamander families have been difficult to
      resolve, largely because the window of time in which major lineages diverged was
      very short relative to the subsequently long evolutionary history of each family.
      We present seven new complete mitochondrial genomes representing five salamander
      families that have no or few mitogenome records in GenBank in order to assess the
      phylogenetic relationships of all salamander families from a mitogenomic
      perspective. Phylogenetic analyses of two data sets-one combining the entire
      mitogenome sequence except for the D-loop, and the other combining the deduced
      amino acid sequences of all 13 mitochondrial protein-coding genes-produce nearly
      identical well-resolved topologies. The monophyly of each family is supported,
      including the controversial Proteidae. The internally fertilizing salamanders are
      demonstrated to be a clade, concordant with recent results using nuclear genes.
      The internally fertilizing salamanders include two well-supported clades: one is
      composed of Ambystomatidae, Dicamptodontidae, and Salamandridae, the other
      Proteidae, Rhyacotritonidae, Amphiumidae, and Plethodontidae. In contrast to
      results from nuclear loci, our results support the conventional morphological
      hypothesis that Sirenidae is the sister-group to all other salamanders and they
      statistically reject the hypothesis from nuclear genes that the suborder
      Cryptobranchoidea (Cryptobranchidae+Hynobiidae) branched earlier than the
      Sirenidae. Using recently recommended fossil calibration points and a "soft
      bound" calibration strategy, we recalculated evolutionary timescales for
      tetrapods with an emphasis on living salamanders, under a Bayesian framework with
      and without a rate-autocorrelation assumption. Our dating results indicate: (i)
      the widely used rate-autocorrelation assumption in relaxed clock analyses is
      problematic and the accuracy of molecular dating for early lissamphibian
      evolution is questionable; (ii) the initial diversification of living amphibians
      occurred later than recent estimates would suggest, from the Late Carboniferous
      to the Early Permian (approximately 294 MYA); (iii) living salamanders originated
      during the Early Jurassic (approximately 183 MYA), and (iv) most salamander
      families had diverged from each other by Late Cretaceous. A likelihood-based
      ancestral area reconstruction analysis favors a distribution throughout Laurasia
      in the Early Jurassic for the common ancestor of all living salamanders.

PMID- 19595774
TI  - Early parental care is important for hippocampal maturation: evidence from brain
      morphology in humans.
AB  - The effects of early life experience on later brain structure and function have
      been studied extensively in animals, yet the relationship between childhood
      experience and normal brain development in humans remains largely unknown. Using
      a unique longitudinal data set including ecologically valid in-home measures of
      early experience during childhood (at age 4 and 8 years) and high-resolution
      structural brain imaging during adolescence (mean age 14 years), we examined the
      effects on later brain morphology of two dimensions of early experience: parental
      nurturance and environmental stimulation. Parental nurturance at age 4 predicts
      the volume of the left hippocampus in adolescence, with better nurturance
      associated with smaller hippocampal volume. In contrast, environmental
      stimulation did not correlate with hippocampal volume. Moreover, the association
      between hippocampal volume and parental nurturance disappears at age 8,
      supporting the existence of a sensitive developmental period for brain
      maturation. These findings indicate that variation in normal childhood experience
      is associated with differences in brain morphology, and hippocampal volume is
      specifically associated with early parental nurturance. Our results provide
      neuroimaging evidence supporting the important role of warm parental care during
      early childhood for brain maturation.

PMID- 19595778
TI  - Phylogenetic evidence for parallel adaptive origins of digestive RNases in Asian
      and African leaf monkeys: a response to Xu et al. (2009).

PMID- 19595779
TI  - Dimethylfumarate inhibits tumor cell invasion and metastasis by suppressing the
      expression and activities of matrix metalloproteinases in melanoma cells.
AB  - NF-kappaB acts as a signal transducer during tumor progression, cell invasion,
      and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis
      factor-alpha-induced nuclear entry of NF-kappaB/p65. However, only a few reports
      suggest that DMF inhibits tumor metastasis; also the molecular mechanisms
      underlying the inhibition of metastasis are poorly understood. We investigated
      the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line,
      B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the
      expression and activities of MMPs. DMF also inhibited the nuclear entry of NF
      kappaB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results
      suggest that DMF is potentially useful as an anti-metastatic agent for the
      treatment of malignant melanoma.

PMID- 19595780
TI  - Impaired long-term potentiation and enhanced neuronal excitability in the
      amygdala of Ca(V)1.3 knockout mice.
AB  - Previously, we demonstrated that mice in which the gene for the L-type voltage
      gated calcium channel Ca(V)1.3 is deleted (Ca(V)1.3 knockout mice) exhibit an
      impaired ability to consolidate contextually-conditioned fear. Given that this
      form of Pavlovian fear conditioning is critically dependent on the basolateral
      complex of the amygdala (BLA), we were interested in the mechanisms by which
      Ca(V)1.3 contributes to BLA neurophysiology. In the present study, we used in
      vitro amygdala slices prepared from Ca(V)1.3 knockout mice and wild-type
      littermates to explore the role of Ca(V)1.3 in long-term potentiation (LTP) and
      intrinsic neuronal excitability in the BLA. We found that LTP in the lateral
      nucleus (LA) of the BLA, induced by high-frequency stimulation of the external
      capsule, was significantly reduced in Ca(V)1.3 knockout mice. Additionally, we
      found that BLA principal neurons from Ca(V)1.3 knockout mice were hyperexcitable,
      exhibiting significant increases in firing rates and decreased interspike
      intervals in response to prolonged somatic depolarization. This aberrant increase
      in neuronal excitability appears to be at least in part due to a concomitant
      reduction in the slow component of the post-burst afterhyperpolarization.
      Together, these results demonstrate altered neuronal function in the BLA of
      Ca(V)1.3 knockout mice which may account for the impaired ability of these mice
      to consolidate contextually-conditioned fear.

PMID- 19595781
TI  - D-serine facilitates the effects of extinction to reduce cocaine-primed
      reinstatement of drug-seeking behavior.
AB  - Male Sprague Dawley rats were allowed to self-administer cocaine (0.5 mg/kg)
      during 90 min sessions for a period of 15 days. On day 16, rats were either held
      abstinent in their home cage environment or experienced an extinction session in
      which the active lever had no programmed consequences. Facilitating N-methyl-D
      aspartate (NMDA) receptor activity with the coagonist D-serine (100 mg/kg i.p.)
      before or following the extinction session significantly reduced the subsequent
      cocaine-primed reinstatement of drug-seeking behavior tested on day 17. D-serine
      significantly reduced drug-primed reinstatement only when combined with
      extinction, and its effectiveness when administered following the training
      session suggested that an enhancement of consolidation of extinction learning had
      occurred. In contrast, D-serine treatment did not reduce sucrose-primed
      reinstatement, indicating that the beneficial effects of this adjunct
      pharmacotherapy with extinction training were specific to an addictive substance
      (cocaine) and did not generalize to a natural reward (sucrose).

PMID- 19595783
TI  - Centriole maturation and transformation to basal body.
AB  - Centrioles and basal bodies are fascinating and mysterious organelles. They
      interconvert and seem to be crucial for a wide range of crucial cellular
      processes. However, intense research over the last years suggested that
      centrioles/basal bodies are essential mainly for the generation of cilia.
      Although a neglected organelle over a long time, interest in the primary cilia
      was recently rekindled by the notion that they are affected in a number of human
      diseases. Cilia formation is an intricate process that starts with the
      transformation of centrioles to basal bodies and their docking to the apical
      plasma membrane. Disturbance of basal body formation thus might cause
      ciliopathies. This review focuses on the formation of basal bodies in mammalian
      cells with an emphasis on basal bodies sprouting a primary cilium.

PMID- 19595782
TI  - Cancer attractors: a systems view of tumors from a gene network dynamics and
      developmental perspective.
AB  - Cell lineage commitment and differentiation are governed by a complex gene
      regulatory network. Disruption of these processes by inappropriate regulatory
      signals and by mutational rewiring of the network can lead to tumorigenesis.
      Cancer cells often exhibit immature or embryonic traits and dysregulated
      developmental genes can act as oncogenes. However, the prevailing paradigm of
      somatic evolution and multi-step tumorigenesis, while useful in many instances,
      offers no logically coherent reason for why oncogenesis recapitulates
      ontogenesis. The formal concept of "cancer attractors", derived from an
      integrative, complex systems approach to gene regulatory network may provide a
      natural explanation. Here we present the theory of attractors in gene network
      dynamics and review the concept of cell types as attractors. We argue that cancer
      cells are trapped in abnormal attractors and discuss this concept in the light of
      recent ideas in cancer biology, including cancer genomics and cancer stem cells,
      as well as the implications for differentiation therapy.

PMID- 19595784
TI  - Metabolic control of antifungal drug resistance.
AB  - Fungi have evolved an elegant repertoire of mechanisms to survive the cellular
      stress exerted by antifungal drugs such as azoles, which inhibit ergosterol
      biosynthesis inducing cell membrane stress. The evolution and maintenance of
      diverse resistance phenotypes is contingent upon cellular circuitry regulated by
      the molecular chaperone Hsp90 and its client protein calcineurin. Here, we
      establish a novel role for nutrients and nutrient signaling in azole resistance.
      The vulnerability of Saccharomyces cerevisiae azole resistance phenotypes to
      perturbation was contingent upon specific auxotrophies. Using strains that
      acquired azole resistance by Erg3 loss of function as a model for resistance that
      depends on cellular stress responses, we delineated genetic and environmental
      factors that mitigate the translation of genotype into resistance phenotype.
      Compromising a global regulator that couples growth and metabolism to
      environmental cues, Tor kinase, provides a powerful strategy to abrogate drug
      resistance of S. cerevisiae and Candida albicans with broad therapeutic
      potential.

PMID- 19595786
TI  - cDNA cloning and expression of grp94 in the Pacific oyster Crassostrea gigas.
AB  - The 94-kDa glucose-regulated protein (GRP94) is an endoplasmic reticulum (ER)
      chaperone. We cloned the first mollusk grp94 from a cDNA library of the Pacific
      oyster Crassostrea gigas. Analysis of C. gigas grp94 (cggrp94) clone containing
      3212 bp DNA revealed that the cDNA contains a 2391 bp open reading frame that
      encodes a 797 amino acid protein of 91.6 kDa. The deduced amino acid sequence of
      cgGRP94 is 67%, 68%, and 67% homologous to the GRP94 of Homo sapiens, GP96 of
      Strongylocentrotus purpuratus, and GP96 of Xenopus laevis, respectively. CgGRP94
      contains an N-terminal 22 amino acid sequence, which is characteristic of a
      signal sequence. It also contains a HATPase_c domain. In addition, it contains
      the KDEL (-Lys-Asp-Glu-Leu) peptide motif at the C-terminus, which suggests that
      cgGRP94 localizes in the ER. Northern blot analysis showed that cggrp94 mRNA is
      expressed at high levels in the gill which cggrp94 mRNA is induced during air
      exposure condition. Expression patterns of cggrp94 mRNA differed between gill and
      mantle, and cggrp94 mRNA was induced at high temperature during air exposure
      condition. These indicate that cggrp94 mRNA is induced by hypoxia and heat shock
      stress, and there are different strategies for air exposure condition between
      gill and mantle.

PMID- 19595785
TI  - A novel polymorphism in the chicken adipocyte fatty acid-binding protein gene
      (FABP4) that alters ligand-binding and correlates with fatness.
AB  - Similar to the mammalian FABP4 gene, the chicken (Gallus gallus) FABP4 gene
      consists of four exons separated by three introns and encodes a 132 amino acid
      protein termed the adipocyte fatty acid-binding protein (AFABP). In the current
      study, a novel G/A polymorphism in exon 3 of the chicken FABP4 gene was
      identified associated with different chicken breeds that leads to either Ser or
      Asn at amino acid 89 of the AFABP protein. The Baier chicken averages 0.89+/
      0.12% abdominal fat and expresses the G allele (Ser 89 isoform) while the Broiler
      chicken typically has 3.74+/-0.23% abdominal fat and expresses the A allele (Asn
      89 isoforms). cDNAs corresponding to the two AFABP isoforms were cloned and
      expressed in Escherichia coli as GST fusions, purified by using glutathione
      sepharose 4B chromatography and evaluated for lipid binding using the fluorescent
      surrogate ligand 1-anilinonaphthalene 8-sulphonic acid (1,8-ANS). The results
      showed that AFABP Ser89 exhibited a lower ligand-binding affinity with apparent
      dissociation constants (Kd) of 7.31+/-3.75 microM, while the AFABP Asn89 isoform
      bound 1,8-ANS with an apparent dissociation constant of 2.99+/-1.00 microM
      (P=0.02). These results suggest that the Ser89Asn polymorphism may influence
      chicken AFABP function and ultimately lipid deposition through changing the
      ligand-binding activity of AFABP.

PMID- 19595787
TI  - High titer production of tetracenomycins by heterologous expression of the
      pathway in a Streptomyces cinnamonensis industrial monensin producer strain.
AB  - Streptomyces cinnamonensis C730.1 and C730.7, are industrially mutagenized
      strains that produce moderate and high levels of the polyketide polyether
      antibiotic monensin A, respectively, in an oil-based fermentation medium. The
      possibility that these strains could be used for high titer production of a
      heterologous polyketide product was investigated by expression of the entire
      tetracenomycin (TCM) biosynthetic pathway using an integrative plasmid, pSET154.
      Expression in C730.1 led to stable production of approximately 0.44 g/l TCM C
      (the final biosynthetic product) and approximately 2.69 g/l TCM A2 (the
      penultimate biosynthetic product), and resulted in a 40% decrease in monensin
      production. Expression in the C730.7 led to higher levels of TCMs, approximately
      0.6 g/l TCM C and approximately 4.35 g/l TCM A2, without any detectable decrease
      in the higher titer monensin production. Abrogation of monensin production in
      this strain through deletion of the corresponding biosynthetic genes did not lead
      to higher levels of TCM products. In the case of the C730.7 host, 85% of the TCM
      C and virtually all of the TCM A2 were intracellular, suggesting feedback
      inhibition leads to the accumulation of the final pathway intermediate. These
      observations contrast those made for the native producer Streptomyces glaucescens
      where the predominant product is TCM C and TCM titers are significantly lower
      levels (approximately 0.3 g/l), and demonstrate the potential utility of S.
      cinnamonensis strains as heterologous hosts for high level expression of a
      variety of polyketide synthase derived products.

PMID- 19595788
TI  - The ptychoid defensive mechanism in Euphthiracaroidea (Acari: Oribatida): a
      comparison of muscular elements with functional considerations.
AB  - Ptychoidy is a mechanical predator defence in some groups of Oribatida (Acari),
      where the animals can retract their legs into the idiosoma and encapsulate. This
      mechanism is enabled by a number of morphological adaptations. We used the non
      invasive technique of synchrotron X-ray microtomography to compare muscular
      elements involved in ptychoidy of two species from the Euphthiracaroidea
      (Oribotritia banksi and Rhysotritia ardua) which differ in a number of cuticular
      elements involved in ptychoidy. We hypothesize that a strong functional
      correlation exists between these cuticular structures and their corresponding
      musculature. We found a number of distinct differences concerning quantitative
      and qualitative muscle morphology. For testing the functional impact of different
      muscle configurations we simulated two conditions in silico (encapsulated /
      opened) and analysed the spatial relative force vectors of the prodorsum lateral
      adjustor muscles (pla) which are responsible for retraction and adjustment of the
      prodorsum during encapsulation. We show that the functional morphology of these
      muscles strongly differs between the two species and that this can be explained
      by the structure of corresponding cuticular elements. Furthermore, the dynamics
      of pla, as measured by the extent of contraction during encapsulation, is more
      than two times higher in R. ardua than in O. banksi.

PMID- 19595789
TI  - Molecular cloning and characterization of an ATP-binding cassette (ABC)
      transmembrane transporter from the white shrimp Litopenaeusvannamei.
AB  - ATP-binding cassette transmembrane transporters (ABC transporters) have a
      potential role in drug and xenobiotic resistance. Here, we report for the first
      time the cloning of an ABC transporter from white shrimp Litopenaeusvannamei
      (designated LvABCG), along with a study of its phylogenetic relationships, and
      measurements of its expression in different shrimp tissues exposed to cadmium and
      pH stress (acidic and alkaline conditions). Sequence analysis showed that LvABCG
      shares many similarities with the white/ABC transmembrane transporter, including
      two conserved regions: a highly conserved ATP-binding cassette (ABC) and
      transmembrane domain (TMD). Spatial analyses of transcript levels for ABCG in
      shrimp tissues, using reverse transcript PCR, revealed the highest transcript
      level in the hepatopancreas, less in the intestine and stomach, and none in the
      other tissues examined. The ABC transporter mRNA transcript in the hepatopancreas
      of L.vannamei was significantly up-regulated after 1.5 h and 24 h of exposure to
      alkaline and acidic conditions, respectively. LvABCG was also induced in
      intestine, but was downregulated in the stomach under the alkaline treatment.
      Upon exposure to cadmium (4.25 micromol L(-1) and 8.5 micromol L(-1)) for 48 h,
      the mRNA expression of LvABCG was up-regulated 4.79-fold (at 6 h) and 2.09-fold
      (at 12 h) in the hepatopancreas. LvABCG was also induced in the stomach after
      exposure to 4.25 micromol L(-1) cadmium, but downregulated in the stomach and
      intestine after exposure to 8.5 micromol L(-1) cadmium. These findings indicate
      that LvABCG might play an important role in the physiological changes related to
      metabolism and cell detoxification that occur when Pacific white shrimp are
      exposed to cadmium and pH stress.

PMID- 19595790
TI  - The expression pattern of Follistatin-like 1 in mouse central nervous system
      development.
AB  - Follistatin-like 1 (Fstl1), also named TSC-36 (TGF-beta-stimulated clone 36), was
      first cloned from the mouse osteoblastic MC3T3-E1 cell line and can be up
      regulated by TGF-beta. To better study the function of Fstl1 during the
      development of the mouse central nervous system (CNS), we examined Fstl1
      expression in the developing mouse CNS, in detail, by in situ hybridization. Our
      results show that Fstl1 is strongly expressed in the telencephalon, diencephalon,
      brainstem, limbic system and spinal cord. In the telencephalon, Fstl1 positive
      cells are mainly located in the ventricular zone (VZ) and the subventricular zone
      (SVZ); a relatively weak signal was observed in layers II and III of the
      neocortex at postnatal stages. Fstl1 expression is robust in the developing
      hippocampus and persists to P20. In the developing diencephalon and hindbrain,
      abundant Fstl1 signals were also detected in nuclei including the medial
      habenular nucleus, the medial dorsal nucleus, the cochlear nuclei and so on. In
      addition, a strong expression of Fstl1 was detected in the thalamencephalic
      signal center, as well as in the olfactory cortex from E14.5 to P0. Meanwhile,
      Fstl1 was expressed in the septal area and the cingulate gyrus of the limbic
      system after birth. A high level of expression was also observed in the ventral
      horn of the spinal cord. These results indicate that Fstl1 may play an important
      role during CNS development in the mouse.

PMID- 19595791
TI  - Expression of five frizzleds during zebrafish craniofacial development.
AB  - Wnt/Planar Cell Polarity (PCP) signaling is critical for proper animal
      development. While initially identified in Drosophila, this pathway is also
      essential for the proper development of vertebrates. Zebrafish mutants, defective
      in the Wnt/PCP pathway, frequently display defects in convergence and extension
      gastrulation movements and additional later abnormalities including problems with
      craniofacial cartilage morphogenesis. Although multiple Frizzled (Fzd)
      homologues, Wnt receptors, were identified in zebrafish, it is unknown which Fzd
      plays a role in shaping the early larvae head skeleton. In an effort to determine
      which Frizzleds are involved in this process, we analyzed the expression of five
      zebrafish frizzled homologues fzd2, 6, 7a, 7b, and 8a from 2-4days post
      fertilization (dpf). During the analyzed developmental time points fzd2 and fzd6
      are broadly expressed throughout the head, while the expression of fzd7a, 7b and
      8a is much more restricted. Closer examination revealed that fzd7b is expressed
      in the neural crest and the mesodermal core of the pharyngeal arches and in the
      chondrocytes of newly stacked craniofacial cartilage elements. However, fzd7a is
      only expressed in the neural crest of the pharyngeal arches and fzd8a is
      expressed in the pharyngeal endoderm.

PMID- 19595792
TI  - Expression of E2F transcription factor family genes during chick wing
      development.
AB  - The E2F family of transcriptional regulators activate or repress gene expression
      during specific phases of the cell cycle and control various processes including
      proliferation, apoptosis and differentiation. However, little is known about the
      developmental roles of E2F transcription factors in higher vertebrates. The chick
      wing is an excellent system for studying these processes because, in addition to
      having a rich classical embryology, it is increasingly amenable to molecular and
      genomic approaches. We show that the human and mouse complement of eight E2F
      transcription factors is conserved in the chicken and that chicken E2F genes are
      expressed in different spatial and temporal patterns during wing development. We
      discuss how the expression patterns of the eight chicken E2F transcription
      factors might be related to important morphogenetic events.

PMID- 19595793
TI  - Induction of mucosal and systemic humoral immune responses in murine system by
      intranasal immunization with peptide antigens of P. vivax and CpG
      oligodeoxynucleotide (ODN) in microparticle delivery.
AB  - In the present study we have investigated the immunomodulatory effects of two
      adjuvants, CpG 1826 (two copies of CpG motifs) and CpG 2006 (three copies of CpG
      motifs) to the five peptide antigens of Plasmodium vivax derived from
      circumsporozoite protein (CSP), merozoite surface protein-1 (MSP1#1, MSP1#23),
      apical membrane antigen-1 (AMA-1) and gametocyte surface antigen (Pvs24) in alum
      and microparticle formulations, using intramuscular and intranasal routes of
      immunization. Alum formulation without CpG ODN generated low serum IgG and IgA
      antibody titers and the predominant IgG isotypes were IgG1 but with the addition
      of CpG ODN (1826 or 2006), the antibody titers were increased by four fold with
      the predominance of IgG2a/2b isotypes. The SIgA peak titers in lung and
      intestinal washes were significantly increased with the intranasal mode of
      administration. Specific activity measurement was done to calculate for the
      accurate amounts of total serum IgG, IgA and SIgA in washes and showed direct
      correlation between antibody titer and its concentration. High titer anti-Pvs24
      antibodies have significant inhibitory effects on parasite development in the
      mosquito midgut when tested in membrane feeding assays. The immunofluorescence
      results show that the peptide specific antisera reacted with the air-dried
      parasite antigens isolated from P. vivax patients. The present study demonstrates
      that intranasal route of immunization appears to be an alternate mode of inducing
      protective immunity in P. vivax malaria.

PMID- 19595794
TI  - Cell-based proteome analysis: the first stage in the pipeline for biomarker
      discovery.
AB  - The early detection of a distinct disease is crucial for a successful treatment
      and depends on a sensitive as well as specific diagnosis. In last years
      tremendous attempts were undertaken to identify new biomarker applying
      proteomics, but no relevant candidate has been identified for clinical
      application. Although proteomics is enabling quantitative and qualitative
      analysis of proteins within complex mixtures it could not significantly
      contribute to this field. Therefore, different proteomics approaches have been
      established focusing on the direct analysis of cell populations involved in
      pathogenic processes to identify candidate biomarkers even for in vitro
      diagnosis. Here, we will outline approaches applying cell- and tissue based
      proteome analysis as the first decisive step in the pipeline for the discovery of
      new diagnostic biomarkers. We will show examples for analysing precursor lesions
      of the pancreatic ductal adenocarcinoma (PDAC), nephron glomeruli and fibrotic
      and non-fibrotic liver tissue. This article provides also an overview about
      currently available techniques in the field of cell enrichment and quantitative
      proteome analysis of lowest amounts of sample.

PMID- 19595796
TI  - The protein glass transition as measured by dielectric spectroscopy and
      differential scanning calorimetry.
AB  - The glass transition and its related dynamics of myoglobin in water and in a
      water-glycerol mixture have been investigated by dielectric spectroscopy and
      differential scanning calorimetry (DSC). For all samples, the DSC measurements
      display a glass transition that extends over a large temperature range. Both the
      temperature of the transition and its broadness decrease rapidly with increasing
      amount of solvent in the system. The dielectric measurements show several
      dynamical processes, due to both protein and solvent relaxations, and in the case
      of pure water as solvent the main protein process (which most likely is due to
      conformational changes of the protein structure) exhibits a dynamic glass
      transition (i.e. reaches a relaxation time of 100 s) at about the same
      temperature as the calorimetric glass transition temperature T(g) is found. This
      glass transition is most likely caused by the dynamic crossover and the
      associated vanishing of the alpha-relaxation of the main water relaxation,
      although it does not contribute to the calorimetric T(g). This is in contrast to
      myoglobin in water-glycerol, where the main solvent relaxation makes the
      strongest contribution to the calorimetric glass transition. For all samples it
      is clear that several proteins processes are involved in the calorimetric glass
      transition and the broadness of the transition depends on how much these
      different relaxations are separated in time.

PMID- 19595795
TI  - Ca(2+), within the physiological concentrations, selectively accelerates Abeta42
      fibril formation and not Abeta40 in vitro.
AB  - Alzheimer's disease (AD) in humans is a common progressive neurodegenerative
      disease, associated with cognitive dysfunction, memory loss and neuronal loss.
      Alzheimer peptides Abeta40 and Abeta42 are precursors of the amyloid fibers that
      accumulate in the brain of patients. These peptides misfold and the monomers
      aggregate to neurotoxic oligomers and fibrils. Thus, the aggregation kinetics of
      these peptides is central to understanding the etiology of AD. Using size
      exclusion chromatography as well as filtration methods, we report here that
      Ca(2+) ions at physiological concentrations greatly accelerate the rate of
      aggregation of Abeta42 to form intermediate soluble associated species and
      fibrils. In the presence of 1 or 2 mM Ca(2+), CD spectra indicated that the
      secondary structure of Abeta42 changed from an unfolded to a predominantly beta
      sheet conformation. These concentrations of Ca(2+) greatly decreased the lag time
      for Abeta42 fibril formation, measured with thioflavin T. However, the elongation
      rate was apparently unaffected. Ca(2+) appears to predominantly accelerate the
      nucleation stage of Abeta42 on pathway to the Alzheimer's fibril formation.
      Unlike Abeta42, Ca(2+) was not observed to trigger similar effect at any stage
      during the study of fibrillation kinetics of Abeta40 by any techniques. Abeta40
      and Abeta42 seem to have distinct aggregation pathways.

PMID- 19595797
TI  - Fluorescence measurements of nucleotide association with the Na(+)/K(+)-ATPase.
AB  - The Na(+)/K(+)-ATPase, a membrane-associated ion pump, uses energy from the
      hydrolysis of ATP to pump 3 Na(+) ions out of and 2 K(+) into cells. The
      dependence of ATP hydrolysis on ATP concentration was measured using a
      fluorescence coupled-enzyme assay. The dependence on concentration of nucleotide
      association with the ATPase was examined using ADP and ATP-induced quenching of
      the fluorescence of ATPase labeled with Cy3-maleimide (Cy3-ATPase) or Alexa Fluor
      546 carboxylic acid, succinimidyl ester (AF-ATPase). The kinetics of ATP
      hydrolysis in the presence of Na(+) and K(+) exhibited negative cooperativity
      with a Hill coefficient (n(H)) of 0.66 and a half-maximal concentration (K(0.5))
      of 61 microM; in the absence of K(+), n(H) was 0.58 and K(0.5) was 13 microM.
      Nucleotide-induced fluorescence quenching exhibited negative cooperativity with
      an n(H) of 0.3-0.5. These results suggest that negative cooperativity observed in
      ATP hydrolysis is attributable to negative cooperativity in nucleotide
      association to the ATPase. Interaction between AF-ATPase and ATP labeled with
      Alexa Fluor 647 (AF-ATP) showed significant Forster resonance energy transfer
      (FRET). These results indicate that the ATPase exists as oligoprotomeric
      complexes in this preparation, and that this aggregation has significant effects
      on enzyme function.

PMID- 19595798
TI  - Photothermal studies of CO photodissociation from peroxidases from horseradish
      and soybean.
AB  - In this work, the results of photoacoustic calorimetry (PAC) studies involving CO
      photodissociation from horseradish peroxidase (HRP) and soybean peroxidase (SBP)
      are discussed. Both proteins contain Fe-protoporphyrin IX active sites and
      relatively open distal heme pockets (i.e., direct solvent access). In addition,
      it has been shown previously that SBP binds a Tris molecule in the distal pocket
      near the heme group potentially regulating ligand binding to the heme iron.
      Results of PAC studies indicate a fast (< approximately 50 ns) relaxation for
      both HRP and SBP subsequent to CO photolysis in both phosphate and Tris buffers
      and with varying concentrations of Tris. However, the molar volume/enthalpy
      changes associated with CO release are distinct between the two proteins. In the
      case of HRP, CO photolysis results in an enthalpy change of approximately 2 kcal
      mol(-1) and volume change of approximately -12 mL mol(-1) attributed to
      solvation/structural changes regardless of buffer conditions. In contrast, SBP
      exhibits buffer and ionic strength dependent enthalpy changes ranging from
      approximately -23 kcal mol(-1) in 50 mM phosphate buffer to approximately 6 kcal
      mol(-1) in Tris buffer with volume changes similar to those observed in HRP. The
      results are consistent with a model in which photodissociation of CO from ferrous
      HRP or SBP leads to CO migration from the distal heme pocket to the bulk solvent
      with a corresponding input of a water molecule all occurring in < approximately
      50 ns. The differences in enthalpies are attributed to variations in hydrogen
      bond formation between the incoming water molecule(s) and the protein matrix in
      both HRP and SBP.

PMID- 19595799
TI  - Effect of conformational states on protein dynamical transition.
AB  - In order to examine the properties specific to the folded protein, the effect of
      the conformational states on protein dynamical transition was studied by
      incoherent elastic neutron scattering for both wild type and a deletion mutant of
      staphylococcal nuclease. The deletion mutant of SNase which lacks C-terminal 13
      residues takes a compact denatured structure, and can be regarded as a model of
      intrinsic unstructured protein. Incoherent elastic neutron scattering experiments
      were carried out at various temperature between 10 K and 300 K on IN10 and IN13
      installed at ILL. Temperature dependence of mean-square displacements was
      obtained by the q-dependence of elastic scattering intensity. The measurements
      were performed on dried and hydrated powder samples. No significant differences
      were observed between wild type and the mutant for the hydrated samples, while
      significant differences were observed for the dried samples. A dynamical
      transition at approximately 140 K observed for both dried and hydrated samples.
      The slopes of the temperature dependence of MSD before transition and after
      transition are different between wild type and the mutant, indicating the folding
      induces hardening. The hydration water activates a further transition at
      approximately 240 K. The behavior of the temperature dependence of MSD is
      indistinguishable for wild type and the mutant, indicating that hydration water
      dynamics dominate the dynamical properties.

PMID- 19595800
TI  - Using polarization analysis to separate the coherent and incoherent scattering
      from protein samples.
AB  - Polarization analysis was used to separate experimentally the coherent and spin
      incoherent nuclear static scattering functions, from a representative set of
      samples of interest for protein studies. This method had so far limited
      application in the study of amorphous materials, despite the relevance of the
      information that it provides. It allows, for instance, the experimental
      determination of the structure factor of materials containing a significant
      amount of hydrogen atoms, avoiding the contamination of measurements by a non
      negligible incoherent background. Knowledge of the relative importance of the
      coherent and incoherent terms at different Q-values is also a pre-requisite for
      the interpretation of quasielastic neutron scattering experiments, performed at
      instruments in which the total dynamic scattering function is measured, such as
      conventional time-of-flight and backscattering spectrometers. Combining data from
      different instruments, it was possible to cover a wide Q-range, from the small
      angle region (0.006<Q<0.04 A(-1)) to the wide-angle region (up to approximately
      2.35 A(-1)). Quantitative information was obtained on the fraction of coherent to
      spin-incoherent scattering from different protein samples: deuterated and
      protonated protein powders at different hydration levels and solutions of
      protonated proteins in D(2)O at different concentrations. The results obtained
      are discussed in the context of the validity of the assumptions generally made
      when interpreting quasielastic neutron scattering experiments performed without
      polarization analysis.

PMID- 19595801
TI  - Characterisation of dihydrodipicolinate synthase (DHDPS) from Bacillus anthracis.
AB  - Bacillus anthracis is a Gram-positive spore-forming bacterium that is the
      causative agent of anthrax disease. The use of anthrax as a bioweapon has
      increased pressure for the development of an effective treatment.
      Dihydrodipicolinate synthase (DHDPS) catalyses the first committed step in the
      biosynthetic pathway yielding two essential bacterial metabolites, meso
      diaminopimelate (DAP) and (S)-lysine. DHDPS is therefore a potential antibiotic
      target, as microbes require either lysine or DAP as a component of the cell wall.
      This paper is the first biochemical description of DHDPS from B. anthracis.
      Enzyme kinetic analyses, isothermal titration calorimetry (ITC), mass
      spectrometry and differential scanning fluorimetry (DSF) were used to
      characterise B. anthracis DHDPS and compare it with the well characterised
      Escherichia coli enzyme. B. anthracis DHDPS exhibited different kinetic behaviour
      compared with E. coli DHDPS, in particular, substrate inhibition by (S)-aspartate
      semi-aldehyde was observed for the B. anthracis enzyme (K(si(ASA))=5.4+/-0.5 mM),
      but not for the E. coli enzyme. As predicted from a comparison of the X-ray
      crystal structures, the B. anthracis enzyme was not inhibited by lysine. The B.
      anthracis enzyme was thermally stabilised by the first substrate, pyruvate, to a
      greater extent than its E. coli counterpart, but has a weaker affinity for
      pyruvate based on enzyme kinetics and ITC studies. This characterisation will
      provide useful information for the design of inhibitors as new antibiotics
      targeting B. anthracis.

PMID- 19595802
TI  - Delay in presentation and diagnosis of adult primary intracranial neoplasms in a
      tropical teaching hospital: a pilot study.
AB  - Sixty-three adult patients with intracranial neoplasms were studied prospectively
      over a 2 year period. The various factors related to pre-presentation symptoms
      interval (PSI) and pre-diagnostic interval (PI) were noted. The mean age at
      presentation for all patients was 46.8 years (range 18-72 years, median 46
      years). Meningiomas (30%), Pituitary tumours (18%), High-grade gliomas (14%) and
      craniopharyngiomas (8%) were the most common brain tumours. The median PSI of all
      patients was 2 year (range 2 months-5 years) with a PI of 4 weeks (range 0-8
      months). The PSI and PI were longer for women with a statistical significance
      between the PSI and gender (p=0.016). The tumour grade was significantly
      correlated with PSI (p=0.000) and PI (p=0.043). Late presentation and diagnosis
      were due to cultural and religious beliefs compounded by self medication and
      financial constraint. There is the need for widespread mass enlightenment,
      improvement in accessibility and affordability of neuroimaging facilities coupled
      with subsidization of treatment.

PMID- 19595803
TI  - Comparison of aspiration-sclerotherapy with hydrocelectomy in the management of
      hydrocele: a prospective randomized study.
AB  - BACKGROUND: Hydrocelectomy is practiced as the gold standard technique for the
      treatment of hydrocele worldwide. Aspiration and sclerotherapy is cheap, less
      invasive and safe compared to hydrocelectomy. However, the outcomes are
      inconsistent because of lack of uniformity in methods and sclerosing agents used.
      MATERIALS AND METHODS: This was a randomized controlled study conducted in a
      university hospital for a period of one year. Sixty symptomatic adult males
      without fertility concern or coexisting scrotal pathology were enrolled.
      Aspiration and sclerotherapy and hydrocelectomy were performed in 30 each.
      PRIMARY OUTCOME MEASURES: incidence of complications, loss of working days, cost
      involved, recurrence rate and patient's satisfaction. Patients were followed up
      till 6 months after the procedures. RESULTS: Eight patients (26.7%) after
      hydrocelectomy developed fever which was significantly more (p<0.05) than 2
      patients (6.7%) following sclerotherapy. Four patients (14%) with hydrocelectomy
      had infection (p<0.05). The incidence of pain and haematocele between the two
      groups were comparable. Nine patients (34.6%) after sclerotherapy developed
      recurrence at 3 months. All patients developed recurrence after repeat aspiration
      and sclerotherapy. The level of satisfaction was more in hydrocelectomy 19 (95%)
      versus 13 (61.9%) patients in sclerotherapy (p<0.05). The cost involved was
      fivefold and the loss of working days sevenfold in hydrocelectomy (p<0.01) as
      compared to sclerotherapy. CONCLUSION: Although aspiration and sclerotherapy had
      less complications, morbidity and was cheaper, it had lower success rate and less
      patient's satisfaction than hydrocelectomy.

PMID- 19595804
TI  - Hydrops fetalis and early neonatal multiple organ failure in familial
      hemophagocytic lymphohistiocytosis.
AB  - Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic heterogeneous
      autosomal recessive disorder. We report two siblings with FHLH caused by a PRF1
      mutation. The first child died in utero with hydrops fetalis and the second
      presented soon after birth with fatal multiple organ failure. Post-mortem DNA
      analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in
      both cases, with their non-consanguineous parents being heterozygous for the same
      mutation. Review of the literature shows that perinatal presentation of FHLH is
      rare. Diagnosis is difficult because in most cases histologic examination reveals
      no hemophagocytosis and the disease is rapidly fatal. The association between
      hydrops fetalis and FHLH has been reported in four previous reports. We present
      the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH
      should be included in the differential diagnosis of non-immune hydrops fetalis
      and neonatal multiple organ failure.

PMID- 19595808
TI  - Scope and aims of Alzheimer's & Dementia: the Journal of the Alzheimer's
      Association.

PMID- 19595805
TI  - A structural view on the mechanism of the ribosome-catalyzed peptide bond
      formation.
AB  - The ribosome is a large ribonucleoprotein particle that translates genetic
      information encoded in mRNA into specific proteins. Its highly conserved active
      site, the peptidyl-transferase center (PTC), is located on the large (50S)
      ribosomal subunit and is comprised solely of rRNA, which makes the ribosome the
      only natural ribozyme with polymerase activity. The last decade witnessed a rapid
      accumulation of atomic-resolution structural data on both ribosomal subunits as
      well as on the entire ribosome. This has allowed studies on the mechanism of
      peptide bond formation at a level of detail that surpasses that for the classical
      protein enzymes. A current understanding of the mechanism of the ribosome
      catalyzed peptide bond formation is the focus of this review. Implications on the
      mechanism of peptide release are discussed as well.

PMID- 19595809
TI  - Public health premise for national research priorities: mortality versus
      disability.

PMID- 19595810
TI  - Mild cognitive impairment: useful or not?

PMID- 19595806
TI  - A switch in time: detailing the life of a riboswitch.
AB  - Riboswitches are non-protein coding RNA elements typically found in the 5'
      untranslated region (5'-UTR) of mRNAs that utilize metabolite binding to control
      expression of their own transcript. The RNA-ligand interaction causes
      conformational changes in the RNA that direct the cotranscriptional folding of a
      downstream secondary structural switch that interfaces with the expression
      machinery. This review describes the structural themes common to the different
      RNA-metabolite complexes studied to date and conclusions that can be made
      regarding how these RNAs efficiently couple metabolite binding to gene
      regulation. Emphasis is placed on the temporal aspects of riboswitch regulation
      that are central to the function of these RNAs and the need to augment the wealth
      of data on metabolite receptor domains with further studies on the full
      regulatory element, particularly in the context of transcription.

PMID- 19595807
TI  - The toll-like receptor 3:dsRNA signaling complex.
AB  - Toll-like receptors (TLRs) recognize conserved molecular patterns in invading
      pathogens and trigger innate immune responses. TLR3 recognizes dsRNA, a molecular
      signature of most viruses via its ectodomain (ECD). The TLR3-ECD structure
      consists of a 23 turn coil bent into the shape of a horseshoe with specialized
      domains capping the N and C-terminal ends of the coil. TLR3-ECDs bind as dimeric
      units to dsRNA oligonucleotides of at least 45 bp in length, the minimal length
      required for signal transduction. X-ray analysis has shown that each TLR3-ECD of
      a dimer binds dsRNA at two sites located at opposite ends of the TLR3 "horseshoe"
      on the one lateral face that lacks N-linked glycans. Intermolecular contacts
      between the C-terminal domains of two TLR3-ECDs stabilize the dimer and position
      the C-terminal residues within 20-25 A of each other, which is thought to be
      essential for transducing a signal across the plasma membrane in intact TLR3
      molecules. Interestingly, in TLRs 1, 2 and 4, which bind lipid ligands using very
      different interactions from TLR3, the ligands nevertheless promote the formation
      of a dimer in which the same two lateral surfaces as in the TLR3-ECD:dsRNA
      complex face each other, bringing their C-termini in close proximity. Thus, a
      pattern is emerging in which pathogen-derived substances bind to TLR-ECDs,
      thereby promoting the formation of a dimer in which the glycan-free ligand
      binding surfaces face each other and the two C-termini are brought in close
      proximity for signal transduction.

PMID- 19595811
TI  - Reduced risk of Alzheimer's disease with high folate intake: the Baltimore
      Longitudinal Study of Aging.
AB  - BACKGROUND: Study findings have suggested an association between Alzheimer's
      disease (AD) risk and several vitamins and have speculated about their use as
      preventive agents. Here, we examine whether total intake (intake from diet plus
      supplements) of antioxidant vitamins (E, C, carotenoids) and B vitamins (folate,
      B(6), and B(12)) is associated with a reduced risk of AD. METHODS: Participants
      were 579 nondemented elderly volunteers from the Baltimore Longitudinal Study of
      Aging who completed dietary diaries and recorded supplement intake for a 7-day
      period. Cox regression was used to estimate the relative risk (RR) of AD
      associated with total vitamin intake categorized into levels above or below the
      Recommended Dietary Allowance (RDA). RESULTS: After a mean follow-up of 9.3
      years, AD developed in 57 participants. Higher intake of folate (RR, 0.41; 95%
      confidence interval [CI], 0.22 to 0.76), vitamin E (RR, 0.56; 95% CI, 0.30 to
      1.06), and vitamin B(6) (RR, 0.41; 95% CI, 0.20 to 0.84) were associated
      individually with a decreased risk of AD after adjusting for age, gender,
      education, and caloric intake. When these 3 vitamins were analyzed together, only
      total intake of folate at or above the RDA (RR, 0.45; 95% CI, 0.21 to 0.97) was
      associated with a significant decreased risk of AD. No association was found
      between total intake of vitamins C, carotenoids, or vitamin B(12) and risk of AD.
      CONCLUSIONS: These findings suggest that total intake of folate at or above the
      RDA is associated with a reduced risk of AD. Additional studies are necessary to
      further investigate whether folate or other(s) unmeasured factor(s) may be
      responsible for this reduction in risk.

PMID- 19595812
TI  - Identification of VaD and AD prodromes: the Cache County Study.
AB  - BACKGROUND: It is unclear whether vascular dementia (VaD) has a cognitive
      prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer's
      dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be
      differentiated from prodromal AD, we examined neuropsychological test performance
      of participants in a nested case-control study within a population-based cohort
      aged 65 or older. METHODS: Participants (n = 485) were identified from the Cache
      County Study, a large population-based study of aging and dementia. After an
      average of 3 years of follow-up, a total of 62 incident dementia cases were
      identified (14 VaD, 48 AD). We identified a number of neuropsychological tests
      (executive and memory) that discriminated between diagnosed VaD and AD cases.
      Multivariate analyses sought to differentiate between these same groups 3 years
      before clinical diagnosis. RESULTS: The Consortium to Establish a Registry for
      Alzheimer's Disease Word List Recognition Test correct recognition of foils (mean
      difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical
      Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory
      II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and
      percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001)
      differentiated VaD from AD cases after adjustment for age, sex, education, and
      dementia severity. Three years before dementia diagnosis, word list recognition
      ("no" responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and "yes"
      responses mean difference, -1.14; 95% CI, -2.14 to -0.13; p < 0.03) discriminated
      between prodromal VaD and AD. CONCLUSION: These results suggest that VaD has a
      prodromal syndrome, the cognitive features of which are distinguishable from the
      cognitive prodrome of AD.

PMID- 19595813
TI  - Treatment of hypertension and prevention of dementia.
AB  - Because of the aging population, the frequency of dementia will dramatically
      increase in the coming years. Prevention of cognitive disorders and dementia has
      become a major public health challenge. High blood pressure is a major risk
      factor for cerebrovascular diseases and is also correlated closely with cognitive
      decline and dementia. Several epidemiologic studies have found that cognitive
      functions are often inversely proportional to blood pressure values measured 15
      or 20 years previously. Moreover, the use of antihypertensive drugs has been
      shown to help prevent cognitive decline, opening the way to the prevention of
      dementia (vascular or Alzheimer's type). These results indicate that incidence of
      dementia should constitute a major outcome of future trials comparing different
      classes of antihypertensive drugs.

PMID- 19595814
TI  - Commentary: "Treatment of hypertension and prevention of dementia" by Olivier
      Hanon and Francoise Forette.

PMID- 19595815
TI  - Commentary: "Treatment of hypertension and prevention of dementia" by Oliver
      Hanon and Francoise Forette.

PMID- 19595816
TI  - Ceramide and cholesterol: possible connections between normal aging of the brain
      and Alzheimer's disease. Just hypotheses or molecular pathways to be identified?
AB  - Even though it is known that aging is the single most important risk factor for
      Alzheimer's disease (AD), there is a lack of information on the molecular
      pathway(s) that connect normal aging of the brain to this form of neuropathology.
      Because of the rise in average lifespan, the number of individuals that reach the
      seventh or eighth decade of life and become at high risk for AD is rapidly
      increasing. Current estimations predict that by 2050 about 45 to 50 million
      individuals will be affected by AD worldwide. Here, we discuss the need for more
      age-directed research to understand AD neuropathology. We also elaborate on the
      possible role of cholesterol and ceramide as molecular connections between aging
      and AD, and as novel therapeutic targets for the prevention of late-onset AD.

PMID- 19595817
TI  - Commentary: "Ceramide and cholesterol: possible connections between normal aging
      of the brain and Alzheimer's disease. Just hypotheses or molecular pathways to be
      identified?" by Claudio Costantini, Rekha M.K. Kolasani, and Luigi Puglielli.

PMID- 19595818
TI  - Commentary: "Ceramide and cholesterol: possible connections between normal aging
      of the brain and Alzheimer's disease. Just hypotheses or molecular pathways to be
      identified?" by Claudio Costantini, Rekha M.K. Kolasani, Luigi Puglielli.

PMID- 19595819
TI  - Meta-analysis of memantine: summary and commentary on the Cochrane
      Collaboration's systematic review.

PMID- 19595820
TI  - Recognition: Robert Katzman and Robert Terry.

PMID- 19595821
TI  - Reminiscences: Robert Katzman and Robert Terry.

PMID- 19595822
TI  - A tribute to a neuropathologist, Robert D. Terry.

PMID- 19595823
TI  - Recognition: Robert Terry and Robert Katzman.

PMID- 19595824
TI  - Recognition: Robert Terry.

PMID- 19595825
TI  - Recognition: Robert Terry.

PMID- 19595826
TI  - Recognition: Robert Terry and Robert Katzman.

PMID- 19595827
TI  - Tribute to Robert Terry.

PMID- 19595828
TI  - Remembering in Alzheimer's disease: the "Bobs" at the turn of the new century.

PMID- 19595829
TI  - Tribute to Robert Terry.

PMID- 19595830
TI  - Alzheimer's research: can it help save our nation's entitlement programs?
AB  - Demographics and government budget policies are on a collision course. The aging
      of the massive baby boom generation is threatening the future solvency of the
      nation's entitlement programs. The budget-driven response by policy makers is to
      cut entitlements and reduce spending on discretionary programs, such as funding
      for research supported by the National Institutes of Health (NIH). Sadly, this
      response is likely to exacerbate the problem by limiting program changes that can
      better respond to the aging population and draining resources away from
      scientific inquiry that can help alleviate future fiscal burdens. A more viable
      solution would be to reform health and long-term care programs to better address
      the chronic care needs of the aging population and to fully fund science that can
      delay onset and slow progression of life-threatening diseases like Alzheimer's.

PMID- 19595831
TI  - Re: Robert Terry and Robert Katzman.

PMID- 19595832
TI  - Diagnosis of Alzheimer's disease: two decades of progress.
AB  - A retrospective view of the critical events and advances in the development of
      criteria, instruments and algorithms in the diagnosis of Alzheimer's disease. The
      review is from the vantage point of the National Institute on Aging and its role
      in the development of the national infrastructure, in the US, for clinical
      research on dementia. The paper discusses future research needs and challenges
      for developing new diagnostic armamentarium for early and accurate detection of
      neurodegenerative processes of dementia in the early prodromal stages or during
      early mild cognitive impairments.

PMID- 19595833
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress."
      Diagnosis of Alzheimer's disease: walking a well-paved path.

PMID- 19595834
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress." The
      NIA's Alzheimer Disease Centers.

PMID- 19595835
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress."
      Symptomatology and biomolecular basis of Alzheimer's: a synthesis.

PMID- 19595836
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".

PMID- 19595837
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress."
      Alzheimer's disease: years of progress, and an army of researchers recruited; AD
      remains an elusive adversary.

PMID- 19595838
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress."
      Evolving neuropathological definitions of Alzheimer's disease: where we came from
      and where we might go.

PMID- 19595839
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".

PMID- 19595840
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".

PMID- 19595841
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".
      Alzheimer's disease research: new opportunities for early diagnosis and drug
      discovery.

PMID- 19595842
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".

PMID- 19595843
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress".

PMID- 19595844
TI  - Commentary on "Diagnosis of Alzheimer's disease: two decades of progress."
      Perspectives on "Perspectives".

PMID- 19595845
TI  - Reversal of scopolamine-induced deficits with a single dose of donepezil, an
      acetylcholinesterase inhibitor.
AB  - BACKGROUND: To develop a more rapid screening paradigm for novel cognitive
      enhancers, the authors sought to determine the utility of a well-known
      pharmacologic model of induced dementia (scopolamine challenge), paired with a
      sensitive neuropsychological test, for assessing the ability of a single oral
      dose of a current treatment for Alzheimer's disease (donepezil) to improve
      cognitive performance in healthy elderly subjects. METHODS: Thirty-two (4 groups
      of 8) healthy elderly volunteers were put randomly into a double-blind, placebo
      controlled, modified crossover design study. In Part 1, 16 subjects received
      donepezil (5 mg) or placebo separately in a crossover fashion. In Part 2, the
      remaining 2 groups of 8 subjects received scopolamine (0.3 mg subcutaneously)
      with each group then were assigned randomly to receive donepezil (5 mg) or
      placebo (in a crossover fashion) 3 hours postbaseline. A novel measure of
      visuospatial working memory and executive controls, the Groton Maze Learning Test
      (GMLT), was administered to each subject at baseline and at 2.5, 4, 5.5, 7, and 9
      hours after dosing of donepezil. RESULTS: With scopolamine, subjects showed
      slower psychomotor speed, reduced accuracy and learning efficiency, and longer
      time required to navigate a hidden maze. Concurrent administration of donepezil
      significantly reversed these deficits and resulted in a faster recovery time. In
      addition, single doses of donepezil alone led to improved psychomotor speed,
      accuracy, and learning efficiency. CONCLUSIONS: Robust effects of single-dose
      donepezil on cognition can be readily observed, with the use of a complex hidden
      maze learning task, both with and without a scopolamine-induced deficit model in
      healthy elderly adults.

PMID- 19595846
TI  - Undertreatment of patients with Alzheimer's disease in an elderly United States
      population.
AB  - BACKGROUND: The aim of this study was to assess the undertreatment of elderly
      mild to moderate Alzheimer's disease (AD) patients in the United States utilizing
      baseline data from a community-based trial that has established comparability to
      national survey samples on demographic characteristics. METHODS: Baseline data
      were used from an open-label, 12-week, postapproval study of compliance with
      galantamine, an AChEI and nicotinic receptor modulator, and vitamin E. A total of
      2,114 patients from 406 community-based US practices in which physicians had
      previously treated patients with acetylcholinesterase inhibitors (AChEIs) were
      included in the study. This population reflects a large, ethnically diverse
      patient pool consistent with the demographics of the elderly population in the
      United States, atypical of those enrolled in most AD trials. RESULTS: The
      majority of patients (64.5%) were described by either themselves or their
      caregivers as not having received prior AChEI treatment. Positive associations
      were found between past AChEI treatment and longer time since diagnosis, white
      race, higher education, medical care by a neurologist, and older caregivers. The
      likelihood of having received previous AChEI treatment was higher among white
      patients (61.9%) than among those from other ethnic groups combined (25.8%).
      CONCLUSIONS: The similarity of patient demographic characteristics to the 2000 US
      Census figures for the population aged >65 years makes this data set a
      potentially powerful tool for planning public health initiatives. Findings
      suggest that patients with mild to moderate AD are undertreated and that
      specialist and nonspecialist organizations should discuss and implement ways to
      optimize management of this disease.

PMID- 19595847
TI  - Role of biomarkers in studies of presymptomatic Alzheimer's disease.
AB  - BACKGROUND: Biomarkers that have been developed largely for the study of patients
      with clinically diagnosed Alzheimer's disease (AD) can also be used in the study
      of cognitively normal individuals who may harbor underlying AD pathology.
      METHODS: A meeting of invited experts on AD biomarkers was held on November 11
      and 12, 2004 to review currently available data and to discuss unmet needs for
      biomarker research in presymptomatic AD. RESULTS: Neuroimaging biomarkers have
      been studied to some extent in subjects at risk for AD. These imaging techniques
      include volumetric magnetic resonance imaging and positron emission tomography
      using either fluorodeoxyglucose or newer ligands that bind directly to amyloid
      plaque. Similarly, biochemical measures from cerebrospinal fluid or other
      physiologic fluids are emerging as potentially useful tools. Such biomarkers may
      be used either as diagnostic tools or as indicators of disease severity when
      followed longitudinally. A clinical diagnosis of asymptomatic individuals using
      biomarkers and studies involving asymptomatic subjects may raise logistical and
      ethical concerns. CONCLUSIONS: The technical development of biomarkers that are
      used for presymptomatic AD diagnosis and for longitudinally measuring disease
      severity is evolving rapidly. Ethical and privacy considerations must be made
      before such biomarkers can be applied routinely to asymptomatic populations.

PMID- 19595848
TI  - Lowering the risk of Alzheimer's disease: evidence-based practices emerge from
      new research.
AB  - BACKGROUND: The increasing prevalence of Alzheimer's disease (AD) and other aging
      related dementias as the population ages will have a dramatic impact on both
      provision of health care and the economy if nothing is done to prevent or delay
      the onset of AD or to slow its progression. METHODS: A comprehensive review of
      the literature in several promising areas of inquiry, other than those
      representing Food and Drug Administration (FDA)-approved AD- or dementia-specific
      pharmacologic therapies, that may impact the risk or progression of AD and
      related dementias was undertaken. RESULTS: Results highlight a number of factors
      associated with AD and dementia. These include education and occupation,
      cognitive and leisure activities, exercise, cholesterol and statins, and head
      trauma. CONCLUSIONS: Factors associated with AD and dementia may have potential
      as strategies useful in preventing or delaying AD and dementia or slowing its
      progression. Further research is needed to determine the validity and strength of
      the associations and to ascertain causality.

PMID- 19595850
TI  - When will dementia become a curable disease and Alzheimer's a forgotten word?

PMID- 19595849
TI  - Commentary on "Lowering the risk of Alzheimer's disease: evidence-based practices
      emerge from new research." Prevention of Alzheimer disease.

PMID- 19595851
TI  - Comparison of clinical and neuropathologic diagnoses of Alzheimer's disease in 3
      epidemiologic samples.
AB  - BACKGROUND: Studies of dementia in populations avoid many of the selection biases
      in clinical samples but require special evaluation and diagnostic methods to
      obtain high participation rates. To address this issue, we developed a unique in
      home dementia assessment. We assessed validity of these assessments using
      neuropathologic confirmation of the clinical diagnosis in 3 epidemiologic
      samples. METHODS: Subjects were 175 participants in 3 ongoing studies of
      dementia. Two were population based and identified dementia by cognitive
      screening. The third study sought volunteers via advertisements. Dementia
      evaluations were then conducted at the participants' residences by specially
      trained nurses and psychometricians. Evaluation results were interpreted, and
      preliminary diagnoses were assigned by a geropsychiatrist or neurologist and a
      psychologist. Final diagnoses were assigned by a consensus panel of neurologists,
      geropsychiatrists, and psychologists. We compared the clinical diagnoses with the
      gold-standard neuropathologic diagnoses for those participants who subsequently
      underwent autopsy. RESULTS: Among the demented, the sensitivity of a clinical
      diagnosis of probable or possible Alzheimer's disease (AD) was 93% across the 3
      studies. The rate of overall diagnostic agreement was 81%. Measures of agreement
      did not differ meaningfully across varying levels of dementia severity.
      CONCLUSIONS: Rates of neuropathologic confirmation for clinical AD diagnoses in
      these studies were similar to those reported from clinic-based samples. These
      results support the validity of clinical diagnoses of AD from a structured in
      home assessment of community dwelling and institutionalized individuals using
      relatively economical methods of dementia screening and assessment.

PMID- 19595852
TI  - The NIH Cognitive and Emotional Health Project. Report of the Critical Evaluation
      Study Committee.
AB  - BACKGROUND: The Cognitive and Emotional Health Project (CEHP) seeks to identify
      the demographic, social, and biological determinants of cognitive and emotional
      health in the older adult. As part of the CEHP, a critical evaluation study
      committee was formed to assess the state of epidemiological research on
      demographic, social, and biological determinants of cognitive and emotional
      health. METHODS: Criteria for inclusion in the survey were large cohort studies,
      longitudinal in design, participants predominantly 65 years or older, with
      measurements of both cognition and emotion, and information on a wide variety of
      demographic, psychosocial, and biological factors. North American and European
      studies, which met these criteria, were selected for the review. Outcome measures
      included cognition, cognitive decline, and cognitive function. For emotion,
      symptoms included depression and anxiety, positive and negative affect,
      subjective well being, mastery, and resilience. RESULTS: Ninety-six papers were
      identified that addressed cognitive and emotional outcomes. A large variety of
      risk factors were consistently identified with cognitive outcomes, particularly
      those previously associated with increased risk of cardiovascular disease. There
      was considerable overlap between risk factors for cognitive and emotional
      outcomes. CONCLUSION: This review identifies a large number of lifestyle and
      health behaviors that alter the risk for maintenance of cognitive and emotional
      health. Large longitudinal cohort studies are a unique source to explore factors
      associated with cognitive and emotional health. Secondary analyses of these
      studies should be encouraged as should the development of standardized
      questionnaires to measure cognitive and emotional health. Future research in this
      field should study cognitive and emotional health simultaneously.

PMID- 19595853
TI  - Commentary on "The NIH Cognitive and Emotional Health Project. Report of the
      Critical Evaluation Study Committee".

PMID- 19595854
TI  - Positron emission tomography and magnetic resonance imaging in the diagnosis and
      prediction of dementia.
AB  - BACKGROUND: The diagnosis of dementia, along with the prediction of who will
      develop dementia, has been assisted by the development of the brain imaging
      techniques of magnetic resonance imaging (MRI) and positron emission tomography
      (PET). METHODS: This paper reviews the brain imaging technologies of structural
      MRI and PET scanning as they have been applied to both the diagnosis of dementia
      and prediction of who will develop dementia. RESULTS: Diagnosis has long been
      enhanced by the use of structural imaging techniques like MRI to rule out non
      degenerative causes of disease. More recently, PET imaging with the glucose
      metabolic tracer [(18)F]Fluorodeoxyglucose (FDG) may be useful in providing
      information on the cause of dementia during life, most specifically in
      differentiating Alzheimer's disease from frontotemporal lobar degeneration. In
      addition to diagnosis, potential therapeutic advances have increased interest in
      prediction of dementia. Both MR and FDG-PET have shown evidence of change in
      brain structure and metabolism in several models of individuals at-risk for
      dementia, including those with mild cognitive impairment and genetic risk
      factors. CONCLUSIONS: While these studies have not yet advanced to the level of
      prospective individual-subject predictive ability, the pattern of data emerging
      suggests likely candidate approaches for such studies. The advent of newer
      techniques such as amyloid imaging with PET and functional MRI may ultimately
      have relevance for both diagnosis and prediction.

PMID- 19595855
TI  - Synaptic targeting by A beta oligomers (ADDLS) as a basis for memory loss in
      early Alzheimer's disease.
AB  - Early diagnosis and treatment of Alzheimer's Disease (AD) ultimately will require
      identification of its pathogenic mechanism. Such a mechanism must explain the
      hallmark of early AD--a profound inability to form new memories. For many years,
      the most promising hypothesis maintained that memory failure derived from neuron
      death induced by insoluble deposits of amyloid fibrils. Newer findings, however,
      suggest that memory loss, especially in early AD, may be a failure in synaptic
      plasticity caused by small soluble A beta oligomers ("ADDLs"). ADDLs are
      neurologically potent toxins that rapidly inhibit long-term potentiation and
      reversal of long-term depression, classic paradigms for learning and memory. In
      human samples, ADDLs show striking increases in AD brain and CSF. The ADDL
      hypothesis is considerably reinforced by nerve cell biology studies showing that
      ADDLs specifically attack synapses, essentially acting as gain-of-function
      pathogenic ligands. Selective damage by ADDLs to memory-linked synaptic
      mechanisms provides an appealing explanation for early AD memory loss and
      suggests that ADDLs provide a valid target for therapeutics and diagnostics.

PMID- 19595856
TI  - The Northern Ireland life review/life storybook project for people with dementia.
AB  - There are few interventions that help people with dementia retain or regain a
      sense of self. Thus, a controlled pilot study examined a life review/life
      storybook intervention, delivered by familiar care assistants to 30 people with
      dementia residing in assisted living facilities in Northern Ireland. A
      multivariate analysis of covariance showed significant change by group (F = 5.01,
      p < 0.014), particularly on depression (F = 7.54, p < 0.015), communication (F =
      23.36, p < 0.005), positive mood (F = 9.47, p < 0.008), and cognition (F = 20.77,
      p < 0.005), suggesting a potentially promising technique to assist people with
      dementia.

PMID- 19595857
TI  - Perspective on a pathogenesis and treatment of Alzheimer's disease.

PMID- 19595858
TI  - Commentary on "Perspective on a pathogenesis and treatment of Alzheimer's
      disease." Apolipoprotein E and the mitochondrial metabolic hypothesis.

PMID- 19595859
TI  - Commentary on "Perspective on a pathogenesis and treatment of Alzheimer's
      disease." Comment on the mitochondrial metabolism hypothesis.

PMID- 19595860
TI  - Should older adults be screened for dementia?
AB  - The question of whether to screen for dementia and Alzheimer's disease (AD) has
      been discussed in many forums throughout the world. Generally, medical advisory
      groups and policy-making groups have recognized the importance of early diagnosis
      but have uniformly avoided making recommendations to screen at-risk populations.
      This presentation reflects the support for reconsidering the importance of
      screening individuals at risk or above a certain age. In this statement, the
      majority of the authors support the consideration of dementia risk factors in
      individuals at age 50, with routine yearly screening after 75. Other authors
      remain concerned that the benefits of treatments of early disease do not yet
      support a general screening recommendation. These statements are made to
      encourage progress toward the development of a consensus regarding the widespread
      institution of screening policy. Accordingly, members of the worldwide scientific
      community are invited to add their perspective by contributing short commentaries
      (1500 words) on this subject.

PMID- 19595861
TI  - Commentary on "The NIH Cognitive and Emotional Health Project: Report of the
      Critical Evaluation Study Committee." What would be the effect of raising the
      retirement age by five years on the cognitive and emotional health of individuals
      age 65 and older?

PMID- 19595862
TI  - Commentary on "The NIH Cognitive and Emotional Health Project: Report of the
      Critical Evaluation Study Committee.".

PMID- 19595863
TI  - Commentary on "The NIH Cognitive and Emotional Health Project: Report of the
      Critical Evaluation Study Committee." What can be concluded?

PMID- 19595864
TI  - Commentary on "Meta-analysis of memantine: summary and commentary on the Cochrane
      Collaboration's systematic review." Meaning and measurement in cognitive
      impairment.

PMID- 19595865
TI  - Statin use and the risk of Alzheimer's disease: the MIRAGE study.
AB  - BACKGROUND: The aim of this study was to examine the association between statin
      use before the onset of Alzheimer's disease (AD) symptoms and risk of having AD,
      and to explore the potential impact of APOE genotype and race on this
      association. METHODS: Data were collected through standardized, validated
      questionnaires from 895 subjects with probable or definite AD by research
      criteria, and 1,483 of their nondemented relatives in this family-based, case
      control study of AD patients and their relatives enrolled at 15 research centers
      from 1996 through 2002. To minimize temporal and prescription biases, exposure to
      statin use within each family was ignored in the one year before the first
      appearance of AD symptoms in that family's affected member. Associations were
      estimated using generalized estimating equations for a logistic model, adjusting
      for age, sex, race, education, history of heart disease, stroke, diabetes,
      smoking and APOE genotype. RESULTS: Statin use was associated with lowered odds
      of having AD (adjusted odds ratio [OR], 0.61; 95% confidence interval [CI], 0.38
      to 0.98). Nonstatin cholesterol-lowering medications were not associated
      significantly with lowered odds of having had AD (adjusted OR, 1.7; 95% CI, 0.61
      to 5.0). CONCLUSIONS: Statin medications were associated with lowered risk of AD
      in this population. Neither African-American race, nor the presence of the APOE 4
      allele modified the statin-AD association.

PMID- 19595866
TI  - Utility of the telephone interview for cognitive status for enrollment in
      clinical trials.
AB  - BACKGROUND: The modified Telephone Interview for Cognitive Status (TICS-m)
      assesses cognitive status via the telephone and has been used to recruit for
      clinical trials by screening for amnestic mild cognitive impairment (aMCI). The
      utility of screening for aMCI has not been validated, and it is unknown which
      questions best predict aMCI. METHODS: The Alzheimer's Disease Cooperative Study
      (ADCS) used the TICS-m to recruit for an aMCI clinical trial. If telephone
      respondents screened positive for aMCI on the TICS-m, they were referred to a
      clinical site where they were assessed for the operational criteria of aMCI.
      Univariate analyses identified the TICS-m questions that best predicted aMCI,
      creating a final model using forward stepwise logistic regression. RESULTS: Of
      52,722 calls, 16,312 were screened for trial entry. Of these, 4,883 received the
      TICS-m. The 2,431 that screened positive for aMCI were referred to a clinic, and
      527 arrived for clinical assessment. Of these, 266 met operational criteria for
      aMCI. The positive predictive value of the TICS-m in this population is 50.9%
      (95% confidence interval [CI], 46.2% to 54.8%). The final model included 5
      variables: (1) 10-word list delayed recall (p < 0.001), (2) day of month (p =
      0.002), (3) season (p = 0.009), (4) last name of current president (p = 0.020),
      and (5) month (p = 0.036). This model has a predictive accuracy of 0.61 (95% CI,
      0.51 to 0.71) which is similar to the entire TICS-m. The predictive accuracy of
      the 10-word list delayed recall alone was 0.63 (95% CI, 0.54 to 0.72).
      CONCLUSION: The TICS-m is not optimally efficient for recruitment of subjects for
      aMCI clinical trials. The 10-word delayed recall has a predictive accuracy
      similar to that of the entire TICS-m.

PMID- 19595867
TI  - Potentially modifiable risk factors for dementia in identical twins.
AB  - BACKGROUND: The purpose of this study was to test nongenetic factors that might
      explain discordance for dementia in monozygotic twin pairs. Risk factors included
      education, engaged lifestyle in midlife, and early life circumstances indexed by
      tooth loss, short adult height, and parental social class. METHODS: Data are from
      the HARMONY study, including members of the Swedish Twin Registry age 65 and
      older and alive in 1998, who were screened and assessed clinically for dementia.
      Analyses included a case-control design to evaluate the risk factors and a co
      twin control design that permits testing nongenetic risk factors while
      controlling for genetic influences. Case-control analyses included 310 dementia
      cases and 3,063 nondemented controls. There were 106 monozygotic twin pairs
      discordant for dementia. Risk factors were assessed independently by the Swedish
      Twin Registry three decades previously. RESULTS: Case-control findings showed
      that history of tooth loss before age 35 and low educational attainment were
      significant risk factors for Alzheimer's disease, with short adult height also
      contributing to risk for total dementia. In co-twin control analyses, only
      history of tooth loss before age 35 was a significant risk factor for Alzheimer's
      disease, whereas low educational attainment also contributed to risk for total
      dementia and lack of physical exercise to risk for non-Alzheimer's dementias.
      CONCLUSIONS: Potentially modifiable risk factors from early and midlife, with a
      cumulative detrimental effect on the brain, contribute to risk of dementia. Based
      on the association with tooth loss, further investigation of inflammatory load as
      a risk factor for Alzheimer's disease is warranted.

PMID- 19595868
TI  - Do cholinergic therapies have disease-modifying effects in Alzheimer's disease?
AB  - The most widely studied and used therapies for Alzheimer's disease (AD) are based
      on improving cholinergic function in the central nervous system. The
      acetylcholine-esterase inhibitors (ChEIs) tacrine, donepezil, rivastigmine, and
      galantamine are all approved, and the latter three are widely used for the
      symptomatic treatment of mild to moderate AD. Recent research has found that
      these drugs may act by a variety of other mechanisms including inhibition of
      butylcholinesterase, regulation of nicotinic receptors, decreasing amyloid
      precursor protein (APP) and A beta production, and regulation of tau
      phosphorylation that may influence disease progression. There is also emerging
      evidence from clinical trials that the ChEIs may delay cognitive and functional
      progression. Other cholinergic drugs such as muscarinic agonists have been
      explored, and although they are not approved, there is robust preclinical
      evidence for a beneficial, perhaps disease-modifying effect. This review
      summarizes evidence suggesting that these drugs may do more than improve
      symptoms; they may delay biological progression of the disease.

PMID- 19595869
TI  - From the bedside: "A terrified witness to the future." A baby boom generation
      wake-up call.

PMID- 19595870
TI  - Optimal design of clinical trials for drugs designed to slow the course of
      Alzheimer's disease.
AB  - Compounds now in clinical development are hypothesized to slow the clinical
      progression and pathogenesis of Alzheimer's disease (AD) by their effects to
      diminish production, increase clearance, or decrease aggregation of amyloid beta
      protein. Options for investigating the effects of these and other drugs on
      clinical progression and pathogenesis of AD were examined at a conference that
      included: (1) a review of experimental methods used to investigate disease
      modifying drugs for multiple sclerosis, rheumatoid arthritis, cardiovascular
      disease, and osteoporosis; (2) discussion of possible study designs and outcome
      measures for trials in patients with AD; and (3) discussion of biomarkers
      available for AD. There is no uniformly best way to investigate a drug's impact
      on AD progression but characteristics of studies supportive of a disease-slowing
      effect can be specified. Relevant clinical outcomes in drug-treated patients
      versus placebo-treated patients should be compared over at least 1 and possibly
      as long as 2 years with biomarkers reflective of pathogenesis and of the drug's
      mechanistic effects measured concurrently.

PMID- 19595871
TI  - Commentary on "Optimal design of clinical trials for drugs designed to slow the
      course of Alzheimer's disease".

PMID- 19595872
TI  - Disease modification in multiple sclerosis: issues with relevance to clinical
      trial designs in Alzheimer's disease.
AB  - The last 13 years have witnessed introduction of disease-modifying drugs (DMDT)
      in the multiple sclerosis (MS) field. This remarkable occurrence has not only
      ushered in an era of therapeutic optimism, it has stimulated change in how the
      pathogenesis of MS is viewed, how clinical studies should be conducted, and how
      outcome should be measured. These issues are in a stage of evolution at the time
      of this writing, but many have great relevance to development of DMDT in
      Alzheimer's disease (AD).

PMID- 19595873
TI  - Finding potent drugs for Alzheimer's disease is more important than proving the
      drugs are disease modifying.
AB  - There are many who feel that the achievement of a disease-modifying (DM)
      designation for a drug is an important goal in Alzheimer disease (AD)
      therapeutics. Several designs that might prove DM have been proposed, including
      randomized start, randomized withdrawal, and slope analysis. Using biomarkers
      such as cerebrospinal fluid assays or imaging features as primary outcome
      measures have also been considered a way of proving DM. The available methods for
      establishing DM are fraught with logistical and analytic problems. Unless the
      drug's benefits are large, attempts to prove DM for a truly effective drug may
      fail. Therefore, clinical trial designs that are the simplest to conduct and
      interpret are superior to those more complex approaches intended to prove DM.

PMID- 19595874
TI  - Disease-modifying treatments for Alzheimer's disease: a perspective based on
      experience with R-Flurbiprofen.

PMID- 19595875
TI  - Development of a disease-modifying treatment for Alzheimer's disease: Alzhemed.

PMID- 19595876
TI  - Lessons from osteoporosis clinical trials.
AB  - We now have a diverse menu of osteoporosis therapies as a result of multiple
      randomized, controlled trials. These randomized, controlled trials have taught us
      the value of final endpoints such as incident fractures versus intermediate
      endpoints such as bone mineral density and bone markers. The success of
      randomized, controlled trials depends on identification of high-risk patients.
      Strategies have been developed to identify high-risk patients using risk factors.
      Finally the importance of both skeletal and extraskeletal safety is discussed.

PMID- 19595877
TI  - Perspectives on assessing benefits and risks in clinical trials for Alzheimer's
      disease.
AB  - Balancing benefits and risks in the development of treatments for Alzheimer's
      disease is challenging given the nature of the disease but critically important
      to ensure effective treatments are available. Drawing on a diverse panel of
      scientists, regulators, caregivers, patients and advocates convened by the
      Alzheimer's Association, insights are offered into benefit/risk assessment,
      decision-making, regulatory and societal factors affecting clinical trials on AD.
      Several policy solutions are offered to improve the drug testing, review and
      approval process.

PMID- 19595878
TI  - Telomeres and telomerase in Alzheimer's disease: epiphenomena or a new focus for
      therapeutic strategy?
AB  - New approaches to the elucidation of Alzheimer disease, even those with solid
      data, are often ignored or dismissed as epiphenomenal when they differ from the
      mainstream or theoretical expectations. Here we present a new piece to the
      puzzle, decreases in telomere length, and telomerase expression in neuronal
      populations known to be vulnerable to degeneration and death in Alzheimer's
      disease. We can present the answers to the question "what," but the "why,"
      "when," and "how" are not so easily answered. The goal of this report is to
      prompt discussion and more intensive study of this finding toward a new focus of
      therapeutic strategy.

PMID- 19595879
TI  - Commentary on "Comparison of clinical and neuropathologic diagnoses of
      Alzheimer's disease in 3 epidemiologic samples".

PMID- 19595880
TI  - The reciprocal risks of stroke and cognitive impairment in an elderly population.
AB  - BACKGROUND: Stroke, dementia, and cognitive impairment no dementia (CIND) pose
      major threats to the elderly but have rarely been studied together in the same
      population. We aimed to compare the relative frequencies of stroke, CIND, and
      dementia in an elderly population and to examine whether cognitive impairment
      poses a risk for stroke. METHODS: Prevalences of stroke, CIND, and dementia were
      estimated among participants in the first clinical examination of the Canadian
      Study of Health and Aging (CSHA-1, n = 2,914). Incidence rates were determined at
      the 5-year follow-up (CSHA-2) among those cognitively normal and stroke free at
      CSHA-1 (n = 828). The associations between cognitive impairment and stroke were
      assessed by Cox regression analyses. RESULTS: Among elderly Canadians, the age
      standardized prevalence of stroke, CIND, and dementia were 8%, 17%, and 8%,
      respectively. Alone or combined, they affected one fourth of the elderly. Among
      stroke survivors, 64% had cognitive impairment compared with 21% among stroke
      free persons. Among the cognitively impaired, 25% had a stroke compared with 4%
      among the cognitively normal. The incidence rates of stroke, CIND, and dementia
      were 3, 6, and 3 per 100 person-years, respectively. Compared with cognitively
      normal subjects, the adjusted risk for incident stroke was 1.3 (95% confidence
      interval [CI], 0.9 to1.9) in patients with CIND and 2.3 (95% CI, 1.7 to 3.2) in
      patients with dementia regardless of whether "questionable stroke" was included.
      CONCLUSIONS: Stroke and cognitive impairment pose risk for each other. CIND is
      highly prevalent, and some of its subtypes may represent treatable preludes to
      stroke and/or dementia.

PMID- 19595881
TI  - Telemedicine, dementia and Down syndrome: implications for Alzheimer disease.
AB  - BACKGROUND: Individuals with Down syndrome (DS) who are at risk for dementia of
      the Alzheimer type (DAT) often live at sites remote from major medical centers.
      Telemedicine (TM) is a modality for providing medical care at remote locations
      but is underutilized for populations with Alzheimer disease (AD). METHODS: We
      studied the feasibility of using TM to evaluate symptoms of DAT in 90 individuals
      with DS. Dementia was assessed by an informant questionnaire, a direct measure of
      praxis, pathological reflexes on the neurologic examination, and the presence of
      cortical atrophy on a neuroimaging procedure. The neurologist was blinded to the
      scores on neuropsychological measures. Differences in average cognitive scores
      between a TM and traditional academic medical center-based clinic site (TAC) were
      tested using 2-way analysis variance with site and premorbid IQ as factors.
      Logistic regression was used to explore the relationship, in addition to the
      cognitive scores, of influences such as age, premorbid IQ, and site to the
      prediction of the physician's diagnosis of dementia. RESULTS: Components of the
      neurologic, imaging, and neuropsychological examinations differentiated subjects
      with and without DAT (p<or=0.008) irrespective of whether a subject was evaluated
      at a TM or TAC site. CONCLUSIONS: It is feasible to make a diagnosis of DAT in DS
      by TM. This study supports the need for formal reliability and validity studies
      of TM preparatory to the consideration of this modality for use in clinical
      trials for AD.

PMID- 19595882
TI  - Vascular cognitive impairment: today and tomorrow.
AB  - Vascular cognitive impairment (VCI) is the phenotypic outcome of a cascade of
      events: vascular risk factors lead to vascular disease, which causes vascular
      brain injury (VBI) in networks important for cognition. Both VCI and Alzheimer's
      disease (AD) increase exponentially with age, and their interactions are common
      and controversial. The ability of current consensus criteria to distinguish VCI
      from AD is limited. Currently, the primary and secondary prevention of VCI is
      essentially the same for stroke, whereas symptomatic treatment of VCI is similar
      to AD. An emerging database suggests that VBI contributes significantly to mild
      VCI and can accelerate the appearance of dementia when AD pathology is mild.
      Early evidence suggests that the adverse effects of VBI are submerged once AD
      pathology spreads into isocortex. Recently, epidemiologic studies reported
      associations between vascular risk factors and clinically diagnosed AD as well as
      stroke. If hypertension, diabetes, and hyperlipidemia truly accelerate beta
      amyloidosis and tauopathy, as well as VBI, the importance of their early
      identification and treatment will be greatly magnified.

PMID- 19595883
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow".

PMID- 19595884
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow." Vascular
      cognitive impairment: yesterday, today, and tomorrow.

PMID- 19595885
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow".

PMID- 19595886
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow." Vascular
      cognitive impairment: time for prevention?

PMID- 19595887
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow".

PMID- 19595888
TI  - Commentary on "Vascular cognitive impairment: today and tomorrow".

PMID- 19595889
TI  - Aggressive course of disease in dementia.
AB  - The rate of disease progression in Alzheimer's disease (AD) patients is variable.
      A significant proportion of AD patients appear to experience an aggressive course
      of disease, and this has a major impact on prognosis, the patients, and their
      caregivers and society in general. Here we review the current literature on an
      aggressive course of disease in dementia and how it can be recognized in clinical
      practice. We also discuss the options available for treating patients with this
      condition.

PMID- 19595890
TI  - Commentary on "Aggressive course of disease in dementia".

PMID- 19595891
TI  - Alzheimer's Association Research Roundtable Meeting on Mild Cognitive Impairment:
      what have we learned?
AB  - The biological changes that occur in the brains of Alzheimer's disease (AD)
      patients are thought to begin long before the onset of clinical symptoms.
      Although current therapeutic agents have been approved only for patients with
      mild to moderate AD, Alzheimer-type pathology in patients with mild to moderate
      AD is already quite advanced. One impetus for the development of the concept of
      mild cognitive impairment (MCI) was the attempt to recognize AD early in its
      clinical expression and to determine whether it is possible through therapeutic
      interventions to improve the memory impairment at this stage or delay further
      progression to dementia. To this end, several clinical trials have been conducted
      in patients with MCI. On September 8 and 9, 2004 a meeting of the Alzheimer's
      Association Research Roundtable was held at which experts in the field of MCI
      convened to review the collective experience from these trials and to consider
      potential approaches that might improve MCI clinical trials in the future. This
      article summarizes the presentations and discussions of that meeting.

PMID- 19595892
TI  - Factors associated with gastrostomy tube feeding in dementia: a structured
      literature review.

PMID- 19595893
TI  - Policy statement on voting by persons with dementia residing in long-term care
      facilities.

PMID- 19595894
TI  - A review of the "State of the Art" on Mild Cognitive Impairment: the Fourth
      Annual Symposium.
AB  - The fourth Annual Mild Cognitive Impairment (MCI) Symposium, held at the Eden Roc
      Hotel in Miami Beach Florida on February 24 and 25, 2006, brought together some
      150 neuropsychologists, neurologists, and other specialists in the field to
      discuss the latest research on issues related to the diagnosis and progression of
      MCI across the broad range of cognitive and functional impairments that comprise
      its various subtypes. Four mini-symposia were convened on the topics of Cognitive
      Reserve and MCI, the Genetics and Proteomics of Cognitive Decline, Pathogenesis
      of Vascular/Metabolic Cognitive Impairment, and Systemic and Psychiatric
      Considerations in MCI. In addition, 2 keynote addresses were delivered; one on
      the Rotterdam Study and the other a review of clinical trials in MCI.
      Participants in the symposium also discussed whether the time has come to revise
      current diagnostic criteria for Alzheimer's disease.

PMID- 19595895
TI  - Modifying dementia risk and trajectories of cognitive decline in aging: the Cache
      County Memory Study.
AB  - The Cache County Study of Memory, Health, and Aging, more commonly referred to as
      the "Cache County Memory Study (CCMS)" is a longitudinal investigation of aging
      and Alzheimer's disease (AD) based in an exceptionally long-lived population
      residing in northern Utah. The study begun in 1994 has followed an initial cohort
      of 5,092 older individuals (many over age 84) and has examined the development of
      cognitive impairment and dementia in relation to genetic and environmental
      antecedents. This article summarizes the major contributions of the CCMS towards
      the understanding of mild cognitive disorders and AD across the lifespan,
      underscoring the role of common health exposures in modifying dementia risk and
      trajectories of cognitive change. The study now in its fourth wave of
      ascertainment illustrates the role of population-based approaches in informing
      testable models of cognitive aging and Alzheimer's disease.

PMID- 19595896
TI  - Re: Diagnosis of Alzheimer's disease: two decades of progress.

PMID- 19595898
TI  - Commentary on "Challenges to demonstrating disease-modifying effects in
      Alzheimer's disease clinical trials".

PMID- 19595899
TI  - Cytoskeletal modulators and pleiotropic strategies for Alzheimer drug discovery.
AB  - The Alzheimer's Association Research Roundtable, a consortium of Association
      senior scientists and leaders from pharmaceutical, biotech, and imaging
      companies, met to discuss strategies for developing novel therapeutics for the
      treatment of Alzheimer's disease (AD). The goal of the meeting was to address,
      primarily, strategies that do not hinge on directly modulating levels of beta
      amyloid. The identification of beta-amyloid as the major constituent of senile
      plaques and the subsequent discovery that familial AD can be caused by mutations
      in either the beta-amyloid precursor protein or presenilins, proteases that
      cleaves beta-amyloid from its precursor, has spawned numerous therapeutic
      strategies for treating AD. These include passive and active vaccines for
      clearing beta-amyloid from the brain and the development of small molecule
      inhibitors of beta- and gamma-secretases that can attenuate the production of
      beta-amyloid. But the field recognizes that there is more to AD than beta-amyloid
      alone. What role do neurofibrillary tangles play in the disease, for example, and
      how are they influenced by beta-amyloid? What lies upstream of beta-amyloid
      production in the sporadic AD brain, and how do apolipoproteins and cholesterol
      influence disease progression? Are there environmental or behavioral factors that
      contribute to the initiation or progression of sporadic AD? Because of the
      complexity of AD, the field is continually looking to other therapeutic
      strategies that may complement or substitute for therapies that target beta
      amyloid. This roundtable meeting was charged with discussing and evaluating some
      of those strategies.

PMID- 19595897
TI  - Challenges to demonstrating disease-modifying effects in Alzheimer's disease
      clinical trials.
AB  - Progress in understanding the molecular biology of Alzheimer's disease (AD) has
      provided a number of plausible therapeutic targets for disease-modifying
      interventions. To advance these agents toward eventual US Food and Drug
      Administration (FDA) approval and incorporation into clinical practice by
      physicians and acceptance by patients and caregivers it is necessary to reach
      consensus on the meaning of disease modification and on what information is
      needed to provide a compelling factual basis for distinguishing disease
      modification from symptomatic treatment effects. Disease modification requires
      that the intervention have an impact of underlying pathology and pathophysiology
      of AD; disease course modification, illness modification or disability sparing
      are alternate terminologies that could be applied to symptomatic agents that do
      not affect the underlying neurobiology of AD. A variety of trial designs have
      been proposed to provide information supporting disease modification including
      change from baseline designs, survival type designs, staggered start designs, and
      staggered withdrawal designs. Each of these has shortcomings, and by themselves
      trial designs are not likely to provide sufficient information to conclusively
      prove that disease modification has occurred. Incorporation of a biomarker into
      clinical trials will support the claim for disease modification. Such a surrogate
      marker ideally should respond to the intervention, predict the clinical response
      to the intervention, and be compellingly related to the neurobiology of AD in the
      pathway affected by the intervention. A third axis of information supportive of
      disease modification is derived from observation of the effect of treatment in
      animal models of AD. The triad of a clinical outcome consistent with disease
      modification, support from a surrogate marker incorporated into the clinical
      trial, and basic science information indicating the effect of the therapy on a
      model of AD would combine to make a convincing case for disease modification.

PMID- 19595900
TI  - Commentary on "Cytoskeletal modulators and pleiotropic strategies for Alzheimer
      drug discovery." Atorvastatin's effect in Alzheimer's dementia (LEADe) study.

PMID- 19595901
TI  - Commentary on "Cytoskeletal modulators and pleiotropic strategies for Alzheimer
      drug discovery." Pleiotropic approaches to Alzheimer's and other diseases of
      aging.

PMID- 19595903
TI  - Commentary on "Perspective on a pathogenesis and treatment of Alzheimer's
      disease." Therapeutic strategies for Alzheimer's disease: the need for a new era
      of innovation.

PMID- 19595902
TI  - Commentary on "Optimal design of clinical trials for drugs designed to slow the
      course of Alzheimer's disease." Biochemical biomarkers of late-life dementia.

PMID- 19595904
TI  - Independent contributions of neural and "higher-order" deficits to symptoms in
      Alzheimer's disease: a latent variable modeling approach.
AB  - BACKGROUND: Analytic models of Alzheimer's disease (AD) tend to focus on one type
      of symptom and assume implicitly that no measurement error is present. These
      tendencies render changes in symptom domains difficult to model mathematically,
      although latent variable methods can accommodate both multiple symptom domains
      and error. This study formulated and compared underlying (latent) factor
      structures representing previously reported dependence and independence of
      symptoms of cognitive decline, functional impairment, and behavioral disturbance
      in AD. METHODS: In confirmatory factor analyses of data from 2 cohorts of AD
      patients, 2 levels of latent variables were conceptualized. One general
      neurologic factor represented disease, and symptom factors represented cognition,
      function, and behavior. Two "null" models had either a single factor or 3 symptom
      factors. Two 2-level models treated the general factor as underlying both the
      observed variables and the symptom factors or treated the symptom factors as
      explaining variability in the observed variables after taking the general factor
      into account ("residualized"). RESULTS/CONCLUSIONS: The residualized model fit
      the data in both cohorts significantly better than the other models, and
      relations in this model between some observed and latent variables were different
      across cohorts. Neither cohort supported a single factor model; both cohorts
      independently supported a residualized model that may permit differentiation of
      symptom- from disease-modifying effects of treatment.

PMID- 19595906
TI  - Common threads in neurodegenerative disorders of aging.

PMID- 19595907
TI  - Dementia diagnosis, treatment, and research with American Indians.

PMID- 19595905
TI  - Factors associated with use of medications with potential to impair cognition or
      cholinesterase inhibitors among Alzheimer's disease patients.
AB  - BACKGROUND: The aim of this study was to use a signal detection method to examine
      the prevalence of, and patient characteristics associated with, medication with
      potential to impair cognition and cholinesterase inhibitor use in patients with
      Alzheimer's disease. METHODS: A cross-sectional study was conducted of 1,954
      patients with a diagnosis of probable or possible Alzheimer's disease. Concurrent
      medications were measured, specifically: (1) a medication with potential to
      impair cognition or (2) a cholinesterase inhibitor. Predictor variables included
      age, gender, ethnic group, education, age of symptom onset, number of
      prescriptions, number of medical diagnoses, Mini-Mental State Examination (MMSE),
      Blessed-Roth Dementia Rating Scale (BRDRS), probable versus possible AD
      diagnosis. RESULTS: Fifteen percent of the Alzheimer's disease patients were on a
      medication with potential to impair cognition, and 44% were on a cholinesterase
      inhibitor. Patient characteristics associated with the prescription of a
      medication with potential to impair cognition included total number of
      prescription medications, low education, low MMSE, older age, reported lack of
      vitamin use, and more medical diagnoses. Patient characteristics associated with
      the prescription of a cholinesterase inhibitor included reported use of vitamins,
      the total number of prescription medications, fewer medical diagnoses, lower age
      of symptom onset, and higher education. CONCLUSIONS: Determining the patient
      characteristics associated with the prescription of a medication with potential
      to impair cognition can help clinicians identify patients who are at risk for
      drug-related morbidity. Patient characteristics unassociated with dementia appear
      to influence the prescription of cholinesterase inhibitors. Signal detection
      analysis is well suited to this type of research.

PMID- 19595908
TI  - "Alzheimer's 101".

PMID- 19595909
TI  - Commentary on "Cytoskeletal modulators and pleiotropic strategies for Alzheimer
      drug discovery." The last stand: the dichotomy of chaperone function in
      Alzheimer's disease.

PMID- 19595910
TI  - Meta-analysis of six-month memantine trials in Alzheimer's disease.
AB  - BACKGROUND: Clinical trials have suggested benefits of memantine for all stages
      of Alzheimer's disease (AD). A meta-analysis of memantine trials in outpatients
      with probable AD was conducted. METHODS: Six randomized, placebo-controlled
      trials fulfilled inclusion criteria. Cognitive, global, functional, behavioral,
      and safety measures were evaluated by using fixed or random effects models.
      Sensitivity analysis was performed to determine potential effects of disease
      severity and concomitant cholinesterase inhibitor use. RESULTS: Overall,
      memantine showed statistically significant, homogenous benefits on global and
      functional outcomes and statistically significant but heterogeneous benefit on
      cognition. In pooled moderate to severe AD studies, effects were significant and
      homogeneous on global, functional, and behavioral measures; in pooled mild to
      moderate studies, significant and homogeneous effects were found on global rating
      and cognition. Safety profiles suggested excellent safety and tolerability, with
      no differences between the severity groups. CONCLUSIONS: Memantine consistently
      benefited patients in all stages of AD and was well-tolerated.

PMID- 19595911
TI  - Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's
      disease." Wuthering forest plots: distinguishing the forest from the plots.

PMID- 19595912
TI  - Commentary on "Meta-analysis of six-month memantine trials in Alzheimer's
      disease." Memantine has negligible benefits in mild to moderate Alzheimer's
      disease.

PMID- 19595913
TI  - Computerized diagnosis of mild cognitive impairment.
AB  - BACKGROUND: We previously described software that we have developed for use in
      the evaluation of mild cognitive impairment (MCI). Our previous study included an
      aged nondemented population with memory complaints (n = 41) that was relatively
      homogenous in terms of education, clinical history, neurological examination, and
      Mini-Mental Status Examination (MMSE) scores. Performance patterns in the
      computerized tests separated the subjects into two groups, and we hypothesized
      that one group might have had incipient dementia. METHODS/RESULTS: In the present
      study we report a follow-up of 35 of the subjects 2 years later. Eight subjects
      who were thought to have incipient dementia at baseline could be evaluated in the
      follow-up, and six of them have deteriorated according to both MMSE and
      neurologists' evaluations and have now fulfilled clinical diagnostic criteria of
      dementia. The other two deteriorated only according to their computer
      performance. Of the 27 remaining subjects, only one now fulfilled clinical
      diagnostic criteria for dementia, although the present computerized examinations
      identified 10 subjects whose performance has deteriorated compared with the
      previous session. CONCLUSION: The follow-up examination thus supported our
      hypothesis that human-computer interaction features can contribute to the
      detection of incipient dementia.

PMID- 19595914
TI  - A simple method to rule out dementia with temporal orientation.
AB  - OBJECTIVE: To explore the performance of a test of temporal orientation (TTO)
      comprising four items derived from the Mini-Mental State Examination over 4
      years. METHODS: Responses were obtained from two large cohorts participating in
      longitudinal studies of aging in the United States (352 normal elderly, 98
      persons with very mild probable or possible Alzheimer's disease). Sensitivity,
      specificity, and predictive value (positive, PV+, negative, PV-) of the TTO were
      estimated for each of four annual visits. RESULTS: When four correct answers were
      treated as "oriented to time" and 0 to 3 correct answers were treated as "not
      oriented to time," sensitivity (to the presence of AD) ranged from 46.0% to 69.2%
      and PV+ ranged from 32.1% to 49.5%. Specificity (for normal cognition) decreased
      from 93.2% at the first visit to 81.3% at the fourth visit; TTO performed most
      reliably in terms of PV-, the probability of normal cognitive function given
      orientation to time (TTO = 4), which ranged from 92.8% to 95.4%. CONCLUSION:
      Given the stability and strength of the predictive negative value of a
      dichotomized TTO over time, a TTO could contribute to monitoring normal cognitive
      functioning in longitudinal studies in which cognitive status is not the primary
      focus. Prospective validation of the TTO is warranted.

PMID- 19595915
TI  - Anxiety of Alzheimer's disease patients before and after a standardized on-road
      driving test.
AB  - BACKGROUND: A large number of licensed elderly drivers are demented or are likely
      to become demented. On-road driving tests, a method often used to assess driver
      competency, are likely anxiety-provoking for elderly individuals. This article
      examines the relationship between anxiety and driving performance in a mildly
      demented and elderly control (EC) sample. METHODS: Anxiety ratings of fear and
      tension, as assessed by visual analog scales, of 84 patients clinically diagnosed
      with mild Alzheimer's disease (AD) (68 safe/marginal and 16 unsafe drivers) were
      compared with those of 44 age- and education-equated safe/marginal EC
      participants, both before and after a standardized on-road driving test. RESULTS:
      Analyses revealed significant positive correlations between AD patients' pre-road
      test and post-road test tension and post-road test fear ratings and total road
      test score. Subsequent analyses of variance showed no significant pre-road test
      differences in fear ratings between the three groups but significantly higher
      levels of tension among the unsafe AD participants. After adjusting for baseline
      group differences, unsafe AD drivers experienced stable or higher anxiety levels
      after road test, whereas both the EC and safe/marginal AD drivers endorsed a
      significant reduction in anxiety. DISCUSSION: Unlike their safe EC and safe AD
      driver counterparts, unsafe AD patients reported continued elevated levels of
      fear and tension after the road test. Given these findings, we suggest that the
      most appropriate time for driving instructors to counsel patients regarding their
      driving skills might be directly after the road test.

PMID- 19595916
TI  - The enigma of mixed dementia.
AB  - Mixed type dementia (MD) refers to a combination of Alzheimer disease (AD) and
      vascular encephalopathy (VE) and other dementia disorders, but the distinction
      between these diseases is difficult. For the diagnosis of MD, the
      clinical/neuroimaging criteria of probable AD plus vascular cognitive impairment
      (VCI) as separate entities are used. Both disorders increase exponentially with
      age, but their interactions are common and controversial. Pathologic diagnosis is
      based on the combination of autopsy-proven AD with multiple vascular or ischemic
      brain lesions. The population-based incidence and prevalence of MD is unknown. In
      retrospective and prospective autopsy studies, its prevalence ranges from 2% to
      58% with reasonable means of 6% to 12%, although findings from several recent
      studies indicated frequent coexistence of AD with multiple cerebrovascular
      lesions (CVLs) in cognitively impaired elderly subjects. In both AD and VCI,
      vascular lesions frequently involve subcortical regions (basal ganglia, thalamus,
      hippocampus, white matter) or are multiple microinfarcts, whereas in MD
      large/hemispheral infarcts and multiple microinfarcts are more frequent,
      suggesting different pathogenic mechanisms. There is increasing evidence that
      critically located small CVLs can induce/promote cognitive impairment in early
      stage AD but not once AD pathology becomes more advanced. Discussion of the major
      pathogenic factors inducing AD, VCI, and MD suggests synergistic relations
      between these disorders. Currently available clinical and morphologic criteria
      for AD and VCI are of limited value for the diagnosis of MD, and the ability of
      current consensus criteria to distinguish between AD, VCI, and MD is limited.
      Therefore, future development of methods that more accurately characterize the
      impact of both AD-related and vascular brain injuries are warranted.

PMID- 19595917
TI  - Greater frequency of subcortical lesions in severely demented patients with early
      onset Alzheimer's disease.
AB  - BACKGROUND: Recent data have shown that in the early stages of Alzheimer's
      disease (AD), vascular brain lesions might promote the progression of cognitive
      decline or might even precede neuronal damage. METHODS: Ischemic brain lesions,
      recognized on computed tomography or magnetic resonance imaging, were analyzed
      retrospectively in 72 patients with early and late onset sporadic AD. RESULTS:
      All types of ischemic lesions occurred more frequently in the AD patients than in
      the controls. Analysis of subgroups of early and late onset AD patients diagnosed
      by magnetic resonance imaging showed a more frequent occurrence of subcortical
      lesions in severely demented patients with early onset AD. CONCLUSIONS: The non
      stroke subcortical ischemic lesions occurring more frequently in our AD patients
      might be recognized as the concomitant vascular pathology that characterizes
      severely demented patients with early onset sporadic AD.

PMID- 19595918
TI  - Be heard here first: a strategic voice for Alzheimer's advocacy.

PMID- 19595919
TI  - The Nevada Vital Aging Initiative: a private-public partnership to study early
      predictors of dementia.

PMID- 19595920
TI  - Should older adults be screened for dementia? It is important to screen for
      evidence of dementia!
AB  - Multiple arguments for considering routine dementia screening have been
      presented. Furthermore, dementia diagnoses are widely unrecognized. As a result,
      persons with dementia are missing important clinical care and treatment
      interventions. By distinction, the problems of defining, diagnosing, and treating
      mild cognitive impairment (MCI) are not yet resolved, and MCI is not ready for a
      screening recommendation. Dementia screening approaches, including cognitive
      testing and functional assessment, must be evaluated on their scientific merits,
      including sensitivity and specificity for recognizing affected individuals in at
      risk populations. Screening tests must be "cost-worthy", with the benefits of
      true-positive test results justifying the costs of testing and resolving false
      positive cases, with due consideration for proper diagnostic evaluation and
      potential harms. With the tremendous number of new cases projected in the near
      future and the expected emergence of beneficial therapies, considerably more
      research is needed to develop more efficient screening systems.

PMID- 19595921
TI  - An estimate of the total worldwide societal costs of dementia in 2005.
AB  - BACKGROUND: The aim of this report was to estimate the worldwide cost of dementia
      in 2005 from a societal viewpoint. METHODS: Costs were estimated by combining
      prevalence estimates, country and region specific data on Gross Domestic Product
      per person, and average wage with results from previously published cost-of
      illness studies in different countries. Direct medical and nonmedical costs as
      well as costs for informal care were included. RESULTS: The total worldwide
      societal cost of dementia, on the basis of a dementia population of 29.3 million
      persons, was estimated to be US$315.4 billion in 2005, including US$105 billion
      for informal care (33%). Seventy-seven percent of the total costs occurred in the
      more developed regions, with 46% of the prevalence. CONCLUSIONS: Worldwide costs
      for dementia are enormous, and informal care constitutes a major cost component,
      in particular in less developed regions. The health economics of dementia is a
      highly relevant area for further research.

PMID- 19595922
TI  - Subjective memory complaints, education, and risk of Alzheimer's disease.
AB  - BACKGROUND: Subjective memory complaints are common in the elderly. Although
      memory complaints are associated with an increased risk of Alzheimer's disease in
      persons with cognitive impairment as well as in persons with normal cognition,
      they are commonly considered of less importance than objective cognitive
      measures. We hypothesized that the clinical relevance of subjective memory
      complaints might vary with educational background. METHODS: The study was
      performed within the Rotterdam Study, a prospective population-based cohort study
      among 7983 persons 55 years and older. Subjective memory complaints and level of
      education were assessed in the baseline interview (1990 to 1993). During a mean
      follow-up of 9.0 years we identified 568 incident Alzheimer's disease patients.
      We estimated the association between subjective memory complaints and risk of
      dementia by means of Cox proportional hazard models. RESULTS: The association
      between subjective memory complaints and risk of Alzheimer's disease varied
      across levels of education. The risk of Alzheimer's disease associated with
      subjective memory complaints was higher in highly educated persons (age- and sex
      adjusted hazard ratio, 2.33; 95% confidence interval [CI], 1.00-5.49) than in
      persons with a low education (age- and sex-adjusted hazard ratio, 1.53; 95% CI,
      1.15-2.05) (P value for interaction, .02). In highly educated persons without
      objective cognitive impairment (Mini-Mental State Examination score, 29 or 30)
      the risk of Alzheimer's disease was highest (age- and sex-adjusted hazard ratio,
      2.98; 95% CI, 1.76-5.02). CONCLUSIONS: Especially in persons with a high level of
      education who still perform well on formal cognitive tests, subjective memory
      complaints might be an important first sign of imminent Alzheimer's disease.

PMID- 19595924
TI  - Statistical and pharmacoeconomic issues for Alzheimer's screening.

PMID- 19595928
TI  - Historical note on Darwin's consideration of early-onset dementia in older
      persons, thirty-six years before Alzheimer's initial case report.
AB  - In February 1871, the great naturalist Charles Darwin received a letter from Dr.
      James-Crichton Browne, who was serving as Director of the largest lunatic asylum
      in England. Darwin had been introduced to Crichton-Browne 2 years earlier by
      Henry Maudsley, who believed that the young psychiatrist could provide Darwin
      with clinical examples of extreme emotional expression, to aid him in preparing
      to write Expression of the Emotions in Man and Animals (1872). This particular
      letter from Crichton-Browne contained the first and only reference to "premature
      dotage" or "senile decay" found anywhere in Darwin's entire corpus of
      correspondence, which amounted to more than 80,000 pages of handwritten letters
      to nearly 2,000 individuals throughout his lifetime. Moreover, this letter from
      Crichton-Browne, received by Darwin 36 years before the first case report of
      senile dementia by Professor Alois Alzheimer, explicitly noted that such
      premature dotage is the result of "brain wasting." Crichton-Browne believed that
      senile dementia was the result of a central nervous system disease, with the
      emotional lability observed in his patients linked inextricably to the disease
      process. This early hypothesis, of interest to Darwin in 1871, anticipated the
      groundbreaking neurohistopathologic research and case description by Alzheimer 36
      years later, and has been confirmed by all clinical research in this field since
      1907. This concordance between psychological symptoms and Alzheimer's disease
      continues to be an important area of study, leading to recent advances in our
      understanding of the genetics, neurobiology, and neurochemistry of psychiatric
      illness in older adults.

PMID- 19595923
TI  - The Memory and Aging Telephone Screen: development and preliminary validation.
AB  - BACKGROUND: Telephone interviews are widely used in geriatric settings to
      identify eligible research participants and to perform brief follow-up
      assessments of cognition. This article reports on the development and validation
      of the Memory and Aging Telephone Screen (MATS), a structured interview for older
      adults with mild cognitive impairment and/or significant memory complaints. We
      also developed three alternate forms of the MATS objective memory test to reduce
      practice effects engendered by multiple administrations. METHODS: Participants
      were enrolled in a longitudinal study that included 120 older adults with
      amnestic mild cognitive impairment, subjective cognitive complaints but without
      deficit on neuropsychological tests, and demographically matched healthy
      controls. An additional 15 patients with mild probable Alzheimer's disease
      completed the alternative forms study. All participants received the original
      MATS version, and a subset (n = 90) later received two of three alternate forms.
      RESULTS: The MATS was sensitive to group differences, and the alternate forms
      were equivalent. MATS objective memory test scores showed adequate stability
      during a period of 1 year and were moderately correlated with scores on a widely
      used list-learning test (California Verbal Learning Test, Second Edition).
      CONCLUSIONS: The MATS, a repeatable telephone screen that includes objective and
      subjective memory assessments, is useful for detecting individuals in the
      preclinical and early stages of dementia. Results encourage use of the MATS as a
      reliable and valid cognitive screening tool in research and clinical settings.
      Longitudinal assessments are being performed to investigate the predictive
      validity of the MATS for cognitive progression in mild cognitive impairment.

PMID- 19595930
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Value therapy for Alzheimer's disease--a European perspective.
AB  - The overall goal of value therapy is to provide the most efficient use of
      resources, taking into account both the cost and the value derived from a given
      technology or drug, and to assist in healthcare decision-making, because both
      cost and effectiveness are considered. After a short review of European Medicines
      Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP)
      recommendations for the development of medications for Alzheimer's disease, we
      focus on the evidence with respect to cost and benefits obtained so far with
      acetylcholinesterase inhibitor (AChEI) and Memantine in the treatment of
      Alzheimer's disease. We then analyze the recommendations developed by
      professionals for the treatment of Alzheimer's disease at the national level in
      European countries, and finally we discuss how to utilize this process more
      homogenously in the future to assess value therapeutic values in Alzheimer's
      disease.

PMID- 19595929
TI  - Health economics and the value of therapy in Alzheimer's disease.
AB  - In increasingly aging societies throughout the developed and developing world,
      Alzheimer's disease and related dementias are fast becoming a critical public
      health issue, exacting an enormous toll on individuals and healthcare systems.
      Over the past 10 years, five drugs have been developed and approved for the
      symptomatic treatment of Alzheimer's dementia, and several disease-modifying
      drugs are in various stages of clinical development. While symptomatic
      medications were consistently shown to have clinical benefit in numerous efficacy
      studies, the cost effectiveness of antidementia therapies and their value to
      healthcare systems remain unclear. The pharmacoeconomics of antidementia
      therapies is an evolving field, with several unanswered questions. This poses
      many challenges for biopharmaceutical companies developing these therapies,
      regulatory agencies responsible for their approval, and payers responsible for
      ensuring their availability to patients. The challenge partly relates to the
      unique nature of dementia as a disease of impaired cognition, behavior, and
      function. Thus, the selection of appropriate outcome measures that directly
      relate to healthcare utilization, quality of life, caregiver burden, and
      pharmacoeconomic analysis has been difficult. The development of meaningful and
      widely acceptable outcome measures, as well as novel clinical-study designs, is
      needed to better evaluate cost effectiveness and to demonstrate the value of
      therapeutics for Alzheimer's disease. Providing the decision-makers in healthcare
      systems with a body of evidence that demonstrates a positive relationship between
      clinical outcomes and the economic and humanistic benefits of antidementia
      therapeutics will improve patient access to novel drugs as they become available.

PMID- 19595931
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Cost-effectiveness studies.
AB  - The high prevalence of dementia has a great impact on the formal care systems as
      well as on the situation for informal caregivers. Thus the question of cost
      effectiveness is crucial. This paper is based on the health-economic portion of
      the dementia project of the Swedish Council on Technology Assessment in
      Healthcare. After a database search and quality judgment of papers, 35 papers
      were included (22 were pharmacoeconomic studies, and 13 focused on programs, such
      as daycare, caregiver support, and living arrangements). No empirical drug study
      was regarded as a complete health-economic study. Of the four prospective,
      randomized, controlled trials, three yielded a nonsignificant difference
      regarding costs (all for donepezil), whereas there was a significant cost
      reduction in the Memantine study (favoring Memantine treatment), mainly due to
      reduction in caregiver time. The majority of the complete pharmacoeconomic
      modeling studies showed a dominance for drug treatment, indicating cost
      effectiveness. In conclusion, as regards the cost effectiveness of treatment for
      Alzheimer's disease, no evidence could be stated in terms of empirical studies,
      mainly because of a lack of studies. Although most models indicated cost
      effectiveness, the Swedish Council on Technology Assessment in Healthcare did not
      regard this as sufficient evidence of cost effectiveness. There is a need for
      larger and longer empirical studies, and for enlarged sensitivity analyses, in
      terms of model studies.

PMID- 19595932
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Report from the Alzheimer's Association Research Roundtable on patient-reported
      outcomes and dementia research.
AB  - The release of the Food and Drug Administration's draft guidance on the patient
      reported outcomes (PROs) measurement in February 2006 has specific implication
      for outcomes research in dementia. Advances in treatments for probable
      Alzheimer's disease present unique challenges to the measurement of clinical
      outcomes. Standards adapted for PROs measurement can be applied to provide an
      alternative perspective on efficacy, and to access a more comprehensive range of
      outcomes than is currently assessed in dementia trials. The draft guidance
      provides only limited direction with regard to proxy measurements, but the
      principles of PROs assessment should be applied to proxy respondent measures.
      Taking a broad view of outcome measurements can offset limitations related to
      utility assessment and the use of data in pharmacoeconomic evaluations of
      dementia treatments. Measurements that formally encompass patients and caregivers
      can enhance our understanding of the disorder, and improve conclusions about
      treatment effectiveness.

PMID- 19595933
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Quality of life in dementia: development and use of a disease-specific measure of
      health-related quality of life in dementia.

PMID- 19595934
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Patient-reported outcomes in clinical trials for Alzheimer's disease.

PMID- 19595935
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Cholinesterase inhibitors in Alzheimer's disease--evidence-based or evidence
      biased?

PMID- 19595936
TI  - Commentary on "Health economics and the value of therapy in Alzheimer's disease."
      Drug treatment of Alzheimer's disease: The United Kingdom experience--National
      Institute for Health and Clinical Excellence guidance and guidelines for
      dementia.

PMID- 19595937
TI  - Forecasting the global burden of Alzheimer's disease.
AB  - BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and
      evaluate the potential impact of interventions that delay disease onset or
      progression. METHODS: A stochastic, multistate model was used in conjunction with
      United Nations worldwide population forecasts and data from epidemiological
      studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide
      prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will
      quadruple, by which time 1 in 85 persons worldwide will be living with the
      disease. We estimate about 43% of prevalent cases need a high level of care,
      equivalent to that of a nursing home. If interventions could delay both disease
      onset and progression by a modest 1 year, there would be nearly 9.2 million fewer
      cases of the disease in 2050, with nearly the entire decline attributable to
      decreases in persons needing a high level of care. CONCLUSIONS: We face a looming
      global epidemic of Alzheimer's disease as the world's population ages. Modest
      advances in therapeutic and preventive strategies that lead to even small delays
      in the onset and progression of Alzheimer's disease can significantly reduce the
      global burden of this disease.

PMID- 19595938
TI  - The Frontal Systems Behavior Scale discriminates frontotemporal dementia from
      Alzheimer's disease.
AB  - Frontotemporal dementia (FTD) is characterized by pronounced changes in affect,
      self-regulation, and social conduct. These behaviors can predate significant
      cognitive changes and can be the most disabling aspect of FTD, yet there are few
      scales designed to assess such changes. The Frontal Systems Behavior Scale
      (FrSBe) is a 46-item behavior rating scale that is intended to measure behavior
      associated with damage to the frontal systems of the brain, with subscales
      measuring Apathy, Disinhibition, and Executive Dysfunction. Thirty-four FTD
      patients and 34 matched patients with dementia of the Alzheimer's type (DAT) were
      compared on the FrSBe in the present study. Both groups displayed increases in
      apathy and dysexecutive behaviors after the onset of dementia, but the FTD group
      exhibited significantly greater change in disinhibition. A discriminant analysis
      with just two scores from the FrSBe and a memory test correctly classified 81% of
      the patients into diagnostic group.

PMID- 19595939
TI  - Burden of illness among commercially insured patients with Alzheimer's disease.
AB  - BACKGROUND: The purpose of this study was to examine the direct costs of care for
      patients newly diagnosed with Alzheimer's disease (AD) by using retrospective
      healthcare claims data. METHODS: Patients aged 65 years or older with >or=1
      claims containing a listed diagnosis of AD between January 1999 and November 2003
      were selected. The first observed AD claim was deemed the index date. Control
      patients with no evidence of AD or dementia also were identified. Patients had a
      12-month pre-index period and minimum 30-day follow-up. AD patients were matched
      to control patients on the basis of age, gender, and follow-up duration.
      Annualized utilization and costs were calculated; generalized linear models (GLM)
      were undertaken, controlling for demographic and clinical characteristics.
      Analyses focused on differences in costs among AD patients and controls. RESULTS:
      The average age of AD and control patients was 82 years; 38% were men (n = 2,475
      AD; 4,950 controls). Average total costs for AD patients were more than five-fold
      higher compared with controls ($28,263 vs $5,880; P < .001), driven primarily by
      inpatient costs. Total costs were significantly higher (P < .001) for AD patients
      in GLM modeling, with diagnosis group (AD vs control) as the most important
      predictor. Adjusted annual costs per patient were also five-fold higher ($21,150
      vs $4,053 for AD vs control, respectively) during the follow-up period.
      CONCLUSIONS: The annual economic burden of AD to third-party payers is more
      substantial than previously estimated ($3,805 to $8,200).

PMID- 19595940
TI  - Comparison of Alzheimer's disease in American Indians, whites, and African
      Americans.
AB  - BACKGROUND: The recent development of a national Alzheimer's disease database
      makes it possible to compare the course of illness in various ethnic groups.
      METHODS: The National Alzheimer's Coordinating Center database was used to
      compare the clinical presentation and course of Alzheimer's disease (AD) in
      American Indians with whites and African-Americans, and to compare findings in
      American Indians seen in Oklahoma with those seen elsewhere. We ascertained the
      diagnosis of probable and possible AD, gender, education, history of affected
      first-degree relative, depression, history of stroke, Parkinson symptoms, age at
      onset of dementia, initial visit, and death. We also ascertained years from
      symptom onset and initial evaluation to death, initial Mini-Mental State Exam
      (MMSE) score adjusted for education, and years from onset of symptoms. RESULTS:
      Data from 30,993 subjects were analyzed. There were statistically significant but
      only small differences between groups. American Indians had the lowest proportion
      of affected first-degree relatives, depression, and extrapyramidal symptoms.
      Whites had the highest proportion of subjects with affected first-degree
      relatives and depression, but the lowest history of stroke. African Americans had
      the most frequent history of stroke and extrapyramidal symptoms. Indians seen in
      Oklahoma had a lower proportion of affected first-degree relatives than did those
      seen elsewhere. CONCLUSIONS: Although there were no clinically significant
      differences in course of illness between these self-identified ethnic groups,
      this finding with regard to American Indians must be interpreted with caution,
      because the subjects for whom we had information regarding ancestry reported a
      smaller proportion of American Indian (25%) than white (75%) heritage.

PMID- 19595941
TI  - In-home monitoring of persons with dementia: ethical guidelines for technology
      research and development.
AB  - Innovative technologies are rapidly emerging that offer caregivers the support
      and means to assist older adults with cognitive impairment to continue living "at
      home." Technology research and development efforts applied to older adults with
      dementia invoke special grant review and institutional review board concerns, to
      ensure not only safe but also ethically appropriate interventions. Evidence is
      emerging, however, that tensions are growing between innovators and reviewers.
      Reviewers with antitechnology biases are in a position to stifle needed
      innovation. Technology developers who fail to understand the clinical and
      caregiving aspects of dementia may design applications that are not in alignment
      with users' capabilities. To bridge this divide, we offer an analysis of the
      ethical issues surrounding home monitoring, a model framework, and ethical
      guidelines for technology research and development for persons with Alzheimer's
      disease and their caregivers.

PMID- 19595942
TI  - Perspective on everyday technologies for Alzheimer's care: research findings,
      directions, and challenges.
AB  - The Everyday Technologies for Alzheimer's Care (ETAC) initiative was launched by
      the Alzheimer's Association and Intel Corporation in 2003 to identify and fund
      promising research in the use of technology--especially information and
      communication technologies (ICTs)--for monitoring, diagnosing, and treating
      Alzheimer's disease (AD). Agilent Technologies joined the initiative in 2005. In
      October 2006, representatives of the three partners, together with ETAC award
      grantees, met to review the most recent research, and discuss how current and
      developing technologies can address growing needs in Alzheimer's care.

PMID- 19595943
TI  - A novel PSENEN mutation in a patient with complaints of memory loss and a family
      history of dementia.
AB  - Presenilin enhancer-2 (PSENEN) is a fundamental component of the gamma-secretase
      protein complex involved in beta-amyloid precursor protein (beta APP) processing,
      a key event in Alzheimer's disease (AD) etiopathogenesis. In a mild cognitive
      impairment (MCI)-diagnosed woman, belonging to a family with a positive history
      for AD, we found that a novel PSENEN mutation (S73F) was the only genetic
      alteration of relevance. The mutation was absent in 253 age-matched controls. In
      an attempt to learn the biochemical effects of this mutation, we cultured skin
      primary fibroblasts from the patient and her daughter, and we assessed A beta(1
      40) and Abeta(1-42) production. We did not find any relevant differences in
      comparison to age-matched, normal subjects. Although our data do not definitively
      support a pathogenetic role for this mutation, it does not appear to be a common
      polymorphism. Further follow-up is warranted in this family.

PMID- 19595944
TI  - Developing a national Alzheimer's strategy equal to the epidemic.

PMID- 19595945
TI  - A chapter in the development of Alzheimer's disease research: a case study of
      public policies on the development and funding of research programs.
AB  - Although Alzheimer's disease, as a clinical-neuropathologic entity, was described
      100 years ago by Alois Alzheimer, the preponderance of knowledge about the
      disease has accumulated since the 1970s. The dramatic advances in research during
      the last three decades propelled the disease from near obscurity to the forefront
      of modern biomedical science. The remarkable transformation of this field of
      study is reflected by the exponential increase in the number of investigators,
      publications, and funded projects. The current preeminence of dementia research
      is largely due to the increasing numbers and quality of significant breakthroughs
      in understanding the molecular neurobiology of the disease. Multiple promising
      leads have created an atmosphere of optimism about the prospects of discovering
      effective interventions to delay the progression of the disease. Some of the key
      factors that influenced the pace of progress and helped to change the "status" of
      dementia research were: a) increases in research funding, b) recruitment of new
      scientific talent, with a convergence of know-how and technologies, c) several
      crucial discoveries in molecular neurobiology, and d) National Institute on Aging
      initiatives to promote interdisciplinary research programs by creating a
      nationwide network of collaborating investigators and a research
      infrastructure/resource. This is an account of how the evolution of research into
      Alzheimer's disease occurred: a story about the critical findings, people, and
      public policies that influenced the amazing progress in understanding the
      underlying molecular mechanisms of the disease and in setting the stage for the
      discovery of a cure.

PMID- 19595946
TI  - Zenith Award Program of the Alzheimer's Association.

PMID- 19595947
TI  - Introduction: the Third Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia, 2006.

PMID- 19595948
TI  - Mild cognitive impairment and cognitive impairment, no dementia: Part A, concept
      and diagnosis.
AB  - Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) are
      controversial emerging terms that encompass the clinical state between elderly
      normal cognition and dementia. This article reviews recent work on the
      classification of MCI and CIND, their prognosis, and diagnostic approaches and
      presents evidence-based recommendations approved at the meeting of the Third
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia
      (CCCDTD3) held in Montreal in March, 2006. New short tools such as the Montreal
      Cognitive Assessment are making it easier for family physicians to confidently
      attach the label of MCI.

PMID- 19595949
TI  - Mild cognitive impairment and cognitive impairment, no dementia: Part B, therapy.
AB  - Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND)
      might be the optimum stage at which to intervene with preventative therapies.
      This article reviews recent work on the possible treatment and presents evidence
      based recommendations approved at the meeting of the Third Consensus Conference
      on the Diagnosis and Treatment of Dementia held in Montreal in March, 2006. A
      number of promising nonpharmacologic interventions have been examined.
      Associations exist with both cognitive and physical activity that suggest that
      both of these, together or separately, can delay progression to dementia.
      Similarly, case control studies as well as prospective long-term studies suggest
      a number of low toxicity interventions and supplements that might significantly
      impact on MCI progression; folate, B(6), and B(12) to lower homocysteine levels,
      omega-fatty acids, and anti-oxidants (fruit juices or red wine) are good
      examples. In selected genotypes such as individuals with APOE e4, therapy with
      donepezil might slow progression. The concern, however, is that none of these
      therapies (including cholinesterase inhibitors) have demonstrated a clinically
      meaningful effect with randomized, placebo-controlled studies. Just as randomized
      controlled studies have failed to support primary prevention of dementia by using
      estrogen or nonsteroidal anti-inflammatory drugs (NSAIDs), there exists the
      possibility that well-designed randomized controlled trials might fail to
      definitively demonstrate putative or promising mild cognitive impairment
      interventions. Pharmacologic interventions and nonpharmacologic therapies, while
      tantalizing, are currently for the most part insufficiently proven to allow
      serious consideration by physicians. Recommendation were supported for a general
      "healthy lifestyle" including physical exercise, healthy nutrition, smoking
      cessation, and mental stimulation. Close monitoring and treatment of vascular
      risk factors are justified and were also supported.

PMID- 19595950
TI  - Clinical diagnosis of dementia.
AB  - This paper presents recommendations deriving from the Third Canadian Consensus
      Conference on the Diagnosis and Treatment of Dementia, concerning the clinical
      diagnosis of dementia. There are currently no universally accepted biological or
      radiological markers of dementia. In the absence of these, the diagnosis of
      dementia remains a clinical exercise aiming to integrate all available clinical
      and laboratory information. It is proposed that the currently used National
      Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's
      Disease and Related Disorders Association (NINCDS/ADRA) criteria for diagnosis of
      Alzheimer's disease (AD) be retained. The currently available vascular dementia
      (VaD) diagnostic criteria have variable accuracy. An integrative approach to VaD
      diagnosis based on all the available evidence (history, vascular risk factors,
      physical exam, clinical course, neuroimaging, cognitive impairment pattern) is
      recommended. The separation of Lewy body dementia (DLB) from Parkinson's disease
      dementia (PDD) is based on the dominant clinical presenting feature of each
      syndrome, and relies on the duration of this feature: long duration of
      parkinsonian "motor" syndrome preceding dementia for PDD versus early/initial
      dementia accompanied by extrapyramidal symptoms for DLB. It is recognized that it
      is impossible clinically to characterize DLB with (pathologically) coexisting AD
      changes. The Frontotemporal group of dementia syndromes are discussed in regards
      to their typical clinical pictures, recognizing that their neuropathological
      substrate are not predictable from their mode of presentation. Finally, the
      particular rapid time sequence of evolution of the dementias due to prior disease
      is recognized as the clinically most useful distinguishing feature of these
      syndromes.

PMID- 19595952
TI  - Cobalamin and homocysteine in older adults: do we need to test for serum levels
      in the work-up of dementia?
AB  - This article reviews available information on the relationship between cobalamin
      (Cbl), homocysteine (tHcy) and cognitive decline and dementia in older adults
      with the aim to propose recommendations as to the need to perform such
      determinations in the work-up for dementia. The article includes brief reviews of
      the magnitude of the problem, effects of the Canadian folic acid fortification
      program on the Cbl and tHcy status in older adults, relation between Cbl and tHcy
      and cognition and cognitive changes, and available data on treatment trials up to
      March 2007. Recommendations and levels of evidence were assigned and approved by
      consensus following the directives of the Third Canadian Consensus Conference on
      the Diagnosis and Treatment of Dementia. The review concludes that determination
      of Cbl (vit B12) levels are recommended in the work-up for dementia and cognitive
      decline because of the high prevalence of Cbl deficits in this population,
      independently of the possible effects of normalization of Cbl levels on cognitive
      function. Even though elevated tHcy is a risk factor for dementia, there is no
      proo of that normalization of tHcy levels changes the course of the disease.
      Clinical trials on that regard are on going.

PMID- 19595951
TI  - Neuropsychological testing and assessment for dementia.
AB  - This evidence-based review examines the utility of brief cognitive tests and
      neuropsychological testing (NPT) in the detection and diagnosis of mild cognitive
      impairment (MCI) and dementia. All patients presenting with cognitive complaints
      are recommended to have a brief screening test administered to document the
      presence and severity of memory/cognitive deficits. There is fair evidence to
      support the use of a range of new screening tests that can detect MCI and mild
      dementia with higher sensitivity (>or=80%) than the Mini-Mental State Exam
      (MMSE). NPT should be part of a clinically integrative approach to the diagnosis
      and differential diagnosis of dementia. It should be applied selectively to
      address specific clinical and diagnostic issues including: 1) The distinction
      between normal cognitive functioning in the aged, MCI and early dementia: there
      is fair evidence that NPT can document the presence of specific diagnostic
      criteria and provide additional useful information on the pattern of
      memory/cognitive impairment. 2) The evaluation of risk for Alzheimer disease (AD)
      or other types of dementia in persons with MCI: there is fair evidence that NPT
      measures or profiles can predict progression to dementia (predictive accuracy
      ranges from approximately 80 to 100%, sensitivities from 53 to 80%, and
      specificities from 67 to 99%). 3) DIFFERENTIAL DIAGNOSIS: There is fair evidence
      that NPT can complement clinical history and neuroimaging in determining the
      dementia etiology. Different dementia types have distinguishable NPT profiles
      though these may be stage-dependent, and increased sensitivity may be at the
      expense of specificity. 4) When NPT is part of a comprehensive assessment, which
      also entails clinical interviews and consideration of other clinical data, there
      is good evidence that it can contribute to management decisions in MCI and
      dementia, including the determination of retained and impaired cognitive
      abilities, their functional and vocational impact, and opportunities for
      cognitive rehabilitation.

PMID- 19595953
TI  - The role of biologic markers in the diagnosis of Alzheimer's disease.

PMID- 19595954
TI  - Structural neuroimaging in the diagnosis of dementia.
AB  - This article reviews recent use of structural imaging in the diagnosis of
      dementia and presents evidence-based recommendations approved at the meeting of
      the Third Canadian Consensus Conference on the Diagnosis and Treatment of
      Dementia held in Montreal in March, 2006. Although the consensus group concurs
      that it is possible to specify circumstances in which structural imaging has a
      role to rule out pathology, it also has a role in ruling in concomitant
      cerebrovascular disease for patient management.

PMID- 19595955
TI  - Functional neuroimaging in the diagnosis of dementia.

PMID- 19595956
TI  - General risk factors for dementia: a systematic evidence review.
AB  - This review identifies and quantifies general (ie, nongenetic) risk factors for
      all-cause dementia, Alzheimer's disease, and vascular dementia specifically.

PMID- 19595957
TI  - Primary prevention of dementia.
AB  - The purpose of this article is to recommend strategies to practicing physicians
      for the prevention of dementia in people without preexisting cognitive deficits.

PMID- 19595958
TI  - Management of mild to moderate Alzheimer's disease and dementia.
AB  - The authors were charged with making a series of evidence-based recommendations
      that would provide concrete advice on all aspects of the management of mild to
      moderate stages of dementia and Alzheimer's disease (AD). The recommendations
      were primarily targeted to primary care physicians practicing in Canada. The
      assigned topic area did not include either the assessment of a patient with
      suspected dementia or the prevention of AD and other dementias. An extensive
      examination of the available literature was conducted. Explicit criteria for
      grading the strength of recommendations and the level of evidence supporting them
      were used. The 28 evidence-based recommendations agreed on are presented in this
      article.

PMID- 19595959
TI  - Clinical practice guidelines for severe Alzheimer's disease.
AB  - BACKGROUND: Although severe Alzheimer's disease (AD) represents a prevalent,
      serious, and costly public health problem, few practice guidelines exist to help
      physicians manage this disorder. METHODS: A search of English language medical
      databases was performed from 1996 to the present for articles pertaining to the
      management of AD. The focus of this review was on studies that included patients
      with severe disease. Studies were assessed by considering the subjects, trial
      design, analysis, and results. Recommendations were based on the best available
      evidence. RESULTS: Severe AD can be defined and diagnosed reliably by using
      measures of cognition, function, behavior, and global staging. Specific
      assessments would also include medical status, safety issues, and the health
      status of the caregiver. Disease-specific management would include treatment with
      cholinesterase inhibitors and/or memantine. Treatment of neuropsychiatric
      symptoms begins with nonpharmacologic behavioral and environmental approaches.
      Severe agitation, aggression, and psychosis that are potentially dangerous to the
      patient, caregiver, and others in the environment can be treated with atypical
      antipsychotics, with consideration of their increased risk of cerebrovascular
      adverse events and mortality. All pharmacologic approaches require careful
      monitoring and regular periodic reassessments to determine whether ongoing
      treatment is necessary. CONCLUSIONS: Evidence-based guidelines for the management
      of severe AD have the potential to improve the quality of life for the patient
      and their caregiver. More randomized controlled trials aimed specifically at this
      phase of illness are still urgently required.

PMID- 19595960
TI  - Management of dementia with a cerebrovascular component.
AB  - BACKGROUND: Cerebrovascular disease (CVD) has been reconceptualized as an
      important factor in cognitive decline and dementia. The concept of vascular
      cognitive impairment (VCI) has been introduced to capture the whole spectrum of
      cognitive decline associated with CVD, and to emphasize the possibility of early
      intervention on vascular risk factors. METHODS: Intervention studies in
      prevention and symptomatic therapy of dementia associated with CVD are reviewed.
      RESULTS: We present recommendations based on the review of current literature.
      There is some evidence that treating hypertension can prevent cognitive decline.
      Galantamine has shown some benefit in the symptomatic treatment of possible
      Alzheimer's disease with CVD and donepezil has shown some benefits in vascular
      dementia. Other pharmacologic interventions lack sufficient empirical support.
      CONCLUSIONS: A more pro-active stance towards cognitive decline of vascular
      etiology is warranted, with some evidence supporting both prevention and
      symptomatic therapy.

PMID- 19595961
TI  - Disclosure of the diagnosis of dementia.
AB  - Most ethical guidelines strongly promote disclosure of a diagnosis of dementia to
      the affected individual, based on the principle of autonomy. Nevertheless, codes
      of medical ethics allow for various interpretations of this issue and surveys of
      clinical practice illustrate that such disclosure is by no means the rule. We
      argue that diagnostic disclosure for persons with dementia must be considered a
      process that begins when cognitive impairment is first suspected and that evolves
      over time as information is obtained. Whenever possible and appropriate, this
      process should involve not only the affected individual but also their family
      and/or other current or potential future care providers. Once a diagnosis is
      established it should be disclosed in a manner consistent with the expressed
      wishes of the patient, using an individualized patient-centered approach that
      maintains the individual's personal integrity. Diagnostic disclosure of dementia
      is a process that may require additional time as well as follow-up or referral to
      other specialists. We recommend that a progressive disclosure process be employed
      to address issues including: remaining diagnostic uncertainty, treatment options,
      future plans, financial planning, assigning power of attorney, wills and "living
      wills", driving privileges and the need for eventual driving cessation, available
      support services, and potential research participation. The potential for adverse
      psychological consequences to diagnostic disclosure must be assessed and these
      should be addressed through education and support of the patient and their
      family/caregivers throughout the diagnostic disclosure process. At present, few
      data are available regarding patients' perspectives on the diagnostic disclosure
      process and its consequences. This limitation and the apparent discrepancies in
      physician and caregiver opinions about the disclosure process, make it incumbent
      upon health care professionals to evaluate the diagnostic disclosure process
      within their practice.

PMID- 19595962
TI  - Ethical considerations for decision making for treatment and research
      participation.
AB  - Here we review issues of patient decision-making and consent to treatment and
      research by persons with cognitive impairment and dementia. Clinicians and
      researchers must recognize their primary duty to care for the individual and must
      clearly distinguish their role as a clinician and/or researcher. Distinctions
      between standard care and research must be clearly understood by everyone, as
      must the clinician's role in each. Both actual and perceived conflicts of
      interest must be avoided. At present there is insufficient evidence to recommend
      specific methods for determining competency for decision-making, but a diagnosis
      of cognitive impairment or dementia does not preclude such competence. Competency
      is not a unitary or static construct and must be considered as the ability to
      make an informed decision about participation in the particular context of the
      specific treatment or study. Clinicians and researchers should consider consent
      as a process involving both the patient with cognitive impairment and his or her
      family/caregiver, particularly given the potential that competency for decision
      making will change over time. As the availability of advance directives remains
      limited, clinicians and researchers must make efforts to ensure that decisions
      made by proxies are based on the prior attitudes and values of the patient.

PMID- 19595963
TI  - Genetics and dementia: risk factors, diagnosis, and management.
AB  - New developments in molecular genetics have improved our understanding on a
      number of neurodegenerative dementias considerably, especially Alzheimer's
      disease and frontotemporal dementia. However, this explosion of information can
      be overwhelming to clinicians, making it difficult to integrate into regular
      clinical practice. In this article, we briefly reviewed our current understanding
      regarding causative genetic mutations and genetic risk factors on the major forms
      of dementia, which provided the background information for discussion in the
      Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.
      The principles of genetic counselling were applied. Guidelines and
      recommendations on the application of genetics in the assessment, diagnosis, and
      management of patients and families with dementia were summarized.

PMID- 19595964
TI  - Toward a revision of criteria for the dementias.
AB  - This article critically considers current diagnostic criteria for dementia and
      reports recommendations approved by at least 80% of experts attending the Third
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia
      (CCCDTD3). There was consensus that many of the features proposed as essential to
      a diagnosis of dementia in the 1980s no longer are relevant (for example, the
      requirements for memory impairment, electroencephalogram and cerebrospinal fluid
      studies, age-specific exclusions). In addition, other syndromes such as
      frontotemporal dementia have been recognized and need to inform new dementia
      criteria. It is also recognized that a diagnosis of depression need not exclude a
      dementia diagnosis. Other proposals, such as neuropathology should be considered
      as additional evidence and not as a gold standard or that some people with
      dementia have prolonged plateaus so that progressive decline need not be a
      criterion for Alzheimer's disease (AD), were more controversial and did not
      receive similar support. Given the evidence of the last three decades, there is
      merit in reconsidering the criteria by which dementia and AD are diagnosed.

PMID- 19595965
TI  - Commentary on "The Third Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia, 2006." Clinical guidelines are not enough: system-wide,
      population-based programs are needed to improve the care of patients with
      Alzheimer's disease and related dementias.

PMID- 19595966
TI  - Commentary on "The Third Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia, 2006.".
AB  - A comprehensive and useful initiative has been performed by our Canadian
      colleagues. The subjects presented are under active discussion in many countries,
      with the goal of direct applications in daily clinical practice. The review
      provided by this special issue of the Journal will therefore be very useful for
      all. In this commentary we will not discuss all papers, but will underline only
      some important points concerning mild cognitive impairment and the diagnosis and
      management of Alzheimer's disease.

PMID- 19595967
TI  - Commentary on "The Third Canadian Consensus Conference on the Diagnosis and
      Treatment of Dementia, 2006."--an appraisal.

PMID- 19595968
TI  - The healthy brain and our aging population: translating science to public health
      practice.

PMID- 19595969
TI  - Cardiovascular risk factors and cognitive function.
AB  - Modifiable factors related to lifestyle have been extensively studied in terms of
      their effects on the vascular system, particularly the risk of heart disease. In
      recent years, however, it has become increasingly evident that many of these
      coronary risk factors also account for a large proportion of strokes, as well as
      cognitive impairment, dementia, and even Alzheimer's disease occurring in the
      absence of a clinically recognized vascular "event." Observational studies
      support a role for hypertension, dyslipidemia, and diabetes mellitus as risk
      factors for cognitive decline in late life, although there are conflicting
      results from some studies. Available evidence, although limited, also supports a
      role for some medical therapies targeting risk factors as a means to reduce the
      risk of subsequent cognitive decline. In many instances, however, basic lifestyle
      interventions show great promise for ameliorating the risk of cognitive decline.
      Such interventions include regular physical exercise or moderate alcohol
      consumption.

PMID- 19595970
TI  - Vascular cognitive change: perspective from neurology.

PMID- 19595971
TI  - The healthy brain and our aging population: translating science to public health
      practice.

PMID- 19595972
TI  - Physical activity and the maintenance of cognition: learning from animal models.
AB  - Although exercise has long been equated with better physical health, there is now
      extensive research showing that it has substantial benefits for the brain as
      well. From an Alzheimer's disease (AD) standpoint, one of the most important
      effects of exercise is on cognition. Exercise not only improves cognitive
      function in normal individuals, but it has been associated with a lower risk for
      AD and other types of dementia. Studies in animal models also suggest that
      exercise might attenuate some of the cognitive symptoms and pathophysiology of
      dementia. Recent research has attempted to identify molecular and cellular
      changes in the central nervous system elicited by physical activity. Work in
      animal models has identified several key responses, including up-regulation of
      growth factors, increased neurogenesis, and improved learning and memory, which
      might be key to improved cognition in response to exercise.

PMID- 19595973
TI  - Physical activity and the maintenance of cognitive function.
AB  - Experimental studies suggest that physical activity or exercise can prevent or
      delay the onset of age-related cognitive impairment or dementia. Several
      epidemiologic studies have attempted to address this issue by using widely
      varying definitions of physical activity as well as differing methods to assess
      cognitive function or dementia. Despite the variability in study design,
      longitudinal studies report that the risk of dementia, cognitive impairment,
      cognitive decline, and Alzheimer's disease is lower among persons engaging in
      high levels of physical activity, relative to those engaging in low levels of
      physical activity. There is also evidence of a dose-response relationship between
      physical activity and preservation of cognitive function, even though small
      increases in physical activity from a sedentary state can reap comparatively
      large incremental benefits. Reductions in the relative risk of vascular dementia
      associated with physical activity were weaker and more variable. Although many
      studies had a follow-up duration of around 5 years, at least one study has found
      evidence that exercise in midlife reduces the risk of dementia in late life. How
      interactions between physical activity and the APOE e4 allele affect the risk of
      cognitive impairment is inconsistent. The available epidemiologic studies support
      the concept that physical activity might prevent or delay the onset of cognitive
      decline. Whether that effect will translate into a reduction in the prevalence of
      dementia is unknown.

PMID- 19595974
TI  - Effects of physical activity on cognition, well-being, and brain: human
      interventions.
AB  - This article provides a review of the human intervention literature that has
      examined the influence of fitness training on cognition, well-being, brain
      structure, and brain function. Meta-analyses of this literature, which are
      reviewed here, suggest robust effects of fitness training on cognition and well
      being. Although there are currently few human intervention studies that have
      examined fitness effects on human brain function and structure, the studies that
      have been conducted report promising results.

PMID- 19595975
TI  - Translating science into public health practice: lessons from physical activity
      interventions.

PMID- 19595976
TI  - Physical activity and cognitive functioning: translating research to practice
      with a public health approach.
AB  - A growing body of research, from retrospective cross-sectional studies to
      randomized clinical trials, suggests that physical activity among the elderly has
      positive effects on a wide range of physiologic systems and tissues, including
      the cardiovascular, immune, and endocrine systems, and even cognitive
      functioning. The latter is particularly relevant to the management of Alzheimer's
      disease and other forms of dementia. There is increasing support that the
      positive effects of physical activity on cognitive functioning have been obtained
      at the primary (cognitively healthy older adults), secondary (persons with some
      loss of cognitive functioning to mild cognitive impairment), and tertiary (older
      adults with significant cognitive impairment) prevention levels. However, there
      are several specific components and potential roles for physical activity in the
      field of cognitive health and functioning that have not been addressed. Moreover,
      we argue that a population-based public health perspective is needed as efforts
      to investigate the physical activity/cognitive health relationship are developed
      and disseminated for large-scale implementation. This perspective discusses some
      of the problems that might be faced when translating basic research findings into
      public health practice for cognitive impairment and/or dementia in older adults
      and addresses how some of these problems might be overcome.

PMID- 19595977
TI  - Cerebrovascular disease and dementia: a primate model of hypertension and
      cognition.
AB  - There is growing epidemiologic evidence that cardiovascular risk factors such as
      high serum cholesterol and hypertension are also risk factors for cognitive
      decline and/or dementia, including Alzheimer's disease. But exactly how these
      different risk factors are linked to cognition is unclear. One way to address
      these correlations is by using animal models of cardiovascular disease. Many such
      models are available, but perhaps none is better suited to studying human
      cognition than non-human primate models. This article describes a rhesus monkey
      aorta coarctation model of hypertension and demonstrates how this might prove to
      be a very valuable model for studying the effect of hypertension on cognition.

PMID- 19595978
TI  - Can we save the brain? A public health question.
AB  - The environmental, behavioral, and lifestyle factors that contribute to increases
      in the risk for cognitive decline and dementia are also factors known to be
      associated with increases in the risk for heart disease and stroke. The analogies
      between these chronic diseases go deeper. For example, public health programs
      designed to reduce the risks for heart disease and stroke, as well as their
      associated disability and mortality, can serve as valuable models for development
      of public health programs addressing brain health. We can save the brain by using
      public health approaches, but the effort will require new approaches and strong
      collaborative efforts across a diverse array of individuals and organizations.

PMID- 19595979
TI  - Cognitive health: an emerging public health issue.

PMID- 19595980
TI  - Commentary on "The Healthy Brain Initiative." A community-based perspective.

PMID- 19595981
TI  - Brain health interventions: the need for further research.

PMID- 19595982
TI  - Do we know enough to begin prevention interventions for dementia?
AB  - This article reviews prior examples of successful prevention interventions and
      reviews whether comparable data are available to support a prevention campaign
      targeting later life cognitive decline and dementia. The evidence that risk
      factors for vascular disease--hypertension, hyperlipidemia, and diabetes mellitus
      -increase the incidence of dementia supports a prevention campaign now.

PMID- 19595983
TI  - Determination of the extent of phosphopantetheinylation of polyketide synthases
      expressed in Escherichia coli and Saccharomyces cerevisiae.
AB  - A sensitive fluorescent assay was developed to measure the extent of
      phosphopantetheinylation of polyketide synthase (PKS) acyl carrier protein (ACP)
      domains in polyketide production strains. The in vitro assay measures PKS
      fluorescence after transfer of fluorescently labeled phosphopantetheine from
      coenzyme A to PKS ACP domains in crude protein extracts. The assay was used to
      determine the extent of phosphopantetheinylation of ACP domains of the
      erythromycin precursor polyketide synthase, 6-deoxyerythronolide B synthase
      (DEBS), expressed in a heterologous Escherichia coli polyketide production
      strain. The data showed that greater than 99.9% of DEBS is
      phosphopantetheinylated. The assay was also used to interrogate the extent of
      phosphopantetheinylation of the lovastatin nonaketide synthase (LNKS)
      heterologously expressed in Saccharomyces cerevisiae. The data showed that LNKS
      was efficiently phosphopantetheinylated in S. cerevisiae and that lack of
      production of the lovastatin precursor polyketide was not due to insufficient
      phosphopantetheinylation of the expressed synthase.

PMID- 19595984
TI  - Fully automated protein purification.
AB  - Obtaining highly purified proteins is essential to begin investigating their
      functional and structural properties. The steps that are typically involved in
      purifying proteins can include an initial capture, intermediate purification, and
      a final polishing step. Completing these steps can take several days and require
      frequent attention to ensure success. Our goal was to design automated protocols
      that would allow the purification of proteins with minimal operator intervention.
      Separate methods have been produced and tested that automate the sample loading,
      column washing, sample elution and peak collection steps for ion exchange, metal
      affinity, hydrophobic interaction, and gel filtration chromatography. These
      individual methods are designed to be coupled and run sequentially in any order
      to achieve a flexible and fully automated protein purification protocol.

PMID- 19595985
TI  - Evaluation of recombinant caspase specificity by competitive substrates.
AB  - The specificity of 10 recombinant caspases was investigated using a set of
      competitive substrates. The caspase activity was determined by high-performance
      liquid chromatography using highly fluorescent peptides containing 2
      aminoacridone (AMAC) as reporting group. The sequences of the used substrates
      were designed according to literature data for being specific for 10 of the
      caspases. The described approach allows the concentration changes of several
      substrates to be monitored simultaneously in a single sample. Because the
      substrates are in competitive conditions, the preferences of particular caspases
      to given peptide sequences are most clearly demonstrated. In the studied
      competitive assay conditions, all tested caspases except caspase 2 exhibit
      activity toward more than one substrate. None of the used peptide sequences was
      found to be highly specific for a defined caspase. The results obtained indicate
      that there is well-expressed group specificity among the caspases.

PMID- 19595986
TI  - Correlating structure, dynamics, and function in transmembrane segment VII of the
      Na+/H+ exchanger isoform 1.
AB  - We place (15)N nuclear magnetic resonance relaxation analysis and functional
      mutagenesis studies in the context of our previous structural and mutagenesis
      work to correlate structure, dynamics and function for the seventh transmembrane
      segment of the human Na(+)/H(+) exchanger isoform 1. Although G261-S263 was
      previously identified as an interruption point in the helical structure of this
      isolated transmembrane peptide in dodecylphosphocholine micelles, and rapid
      conformational exchange was implicated in the NOE measurements, the six (15)N
      labelled residues examined in this study all have similar dynamics on the ps-ns
      time scale. A mathematical model incorporating chemical exchange is the best fit
      for residues G261, L264, and A268. This implies that a segment of residues from
      G261 to A268 samples different conformations on the mus-ms time scale. Chemical
      exchange on an intermediate time scale is consistent with an alternating-access
      cycle where E262 is bent away from the cytosol during proton translocation by the
      exchanger. The functional importance of chemical exchange at G261-A268 is
      corroborated by the abrogated activity of the full-length exchanger with the
      bulky and restricting Ile substitutions F260I, G261I, E262I, S263I, and A268I.

PMID- 19595988
TI  - Disruption of Saccharomyces cerevisiae by Plantaricin 149 and investigation of
      its mechanism of action with biomembrane model systems.
AB  - The action of a synthetic antimicrobial peptide analog of Plantaricin 149
      (Pln149a) against Saccharomyces cerevisiae and its interaction with biomembrane
      model systems were investigated. Pln149a was shown to inhibit S. cerevisiae
      growth by more than 80% in YPD medium, causing morphological changes in the yeast
      wall and remaining active and resistant to the yeast proteases even after 24 h of
      incubation. Different membrane model systems and carbohydrates were employed to
      better describe the Pln149a interaction with cellular components using circular
      dichroism and fluorescence spectroscopies, adsorption kinetics and surface
      elasticity in Langmuir monolayers. These assays showed that Pln149a does not
      interact with either mono/polysaccharides or zwitterionic LUVs, but is strongly
      adsorbed to and incorporated into negatively charged surfaces, causing a
      conformational change in its secondary structure from random-coil to helix upon
      adsorption. From the concurrent analysis of Pln149a adsorption kinetics and
      dilatational surface elasticity data, we determined that 2.5 muM is the critical
      concentration at which Pln149a will disrupt a negative DPPG monolayer.
      Furthermore, Pln149a exhibited a carpet-like mechanism of action, in which the
      peptide initially binds to the membrane, covering its surface and acquiring a
      helical structure that remains associated to the negatively charged
      phospholipids. After this electrostatic interaction, another peptide region
      causes a strain in the membrane, promoting its disruption.

PMID- 19595987
TI  - Biophysical studies of the membrane location of the voltage-gated sensors in the
      HsapBK and KvAP K(+) channels.
AB  - The membrane location of two fragments in two different K(+)-channels, the KvAP
      (from Aeropyrum pernix) and the HsapBK (human) corresponding to the putative
      "paddle" domains, has been investigated by CD, fluorescence and NMR spectroscopy.
      Both domains interact with q = 0.5 phospholipid bicelles, DHPC micelles and with
      POPC vesicles. CD spectra demonstrate that both peptides become largely helical
      in the presence of phospholipid bicelles. Fluorescence quenching studies using
      soluble acrylamide or lipid-attached doxyl-groups show that the arginine-rich
      domains are located within the bilayered region in phospholipid bicelles. Nuclear
      magnetic relaxation parameters, T(1) and (13)C-(1)H NOE, for DMPC in DMPC/DHPC
      bicelles and for DHPC in micelles showed that the lipid acyl chains in the
      bicelles become less flexible in the presence of either of the fragments. An even
      more pronounced effect is seen on the glycerol carbons. (2)H NMR spectra of
      magnetically aligned bicelles showed that the peptide derived from KvAP had no or
      little effect on bilayer order, while the peptide derived from HsapBK had the
      effect of lowering the order of the bilayer. The present study demonstrates that
      the fragments derived from the full-length proteins interact with the bilayered
      interior of model membranes, and that they affect both the local mobility and
      lipid order of model membrane systems.

PMID- 19595989
TI  - Protein dynamics detected in a membrane-embedded potassium channel using two
      dimensional solid-state NMR spectroscopy.
AB  - We report longitudinal (15)N relaxation rates derived from two-dimensional
      ((15)N, (13)C) chemical shift correlation experiments obtained under magic angle
      spinning for the potassium channel KcsA-Kv1.3 reconstituted in multilamellar
      vesicles. Thus, we demonstrate that solid-state NMR can be used to probe residue
      specific backbone dynamics in a membrane-embedded protein. Enhanced backbone
      mobility was detected for two glycine residues within the selectivity filter that
      are highly conserved in potassium channels and that are of core relevance to the
      filter structure and ion selectivity.

PMID- 19595990
TI  - Immunogenicity difference between the SARS coronavirus and the bat SARS-like
      coronavirus spike (S) proteins.
AB  - SARS-like coronavirus (SL-CoV) in bats have a similar genomic organization to the
      human SARS-CoV. Their cognate gene products are highly conserved with the
      exception of the N-terminal region of the S proteins, which have only 63-64%
      sequence identity. The N-terminal region of coronavirus S protein is responsible
      for virus-receptor interaction. In this study, the immunogenicity of the SL-CoV S
      protein (S(SL)) was studied and compared with that of SARS-CoV (S(SARS)). DNA
      immunization in mice with S(SL) elicited a high titer of antibodies against HIV
      pseudotyped S(SL). The sera had low cross-reactivity, but no neutralization
      activity, for the HIV-pseudotyped S(SARS). Studies using wild bat sera revealed
      that it is highly likely that the immunodominant epitopes overlap with the major
      neutralizing sites of the SL-CoV S protein. These results demonstrated that SL
      CoV and SARS-CoV shared only a limited number of immunogenic epitopes in their S
      proteins and the major neutralization epitopes are substantially different. This
      work provides useful information for future development of differential serologic
      diagnosis and vaccines for coronaviruses with different S protein sequences.

PMID- 19595991
TI  - Effect on movement selection of an evolving sensory representation: a multiple
      controller model of skill acquisition.
AB  - Change in behavior and neural activity in skill acquisition suggests that control
      is transferred from cortical planning areas (e.g., the prefrontal cortex, PFC) to
      the basal ganglia (BG). Planning has large computational and representational
      requirements but requires little experience with a task. The BG are thought to
      employ a simpler control scheme and reinforcement learning; these mechanisms rely
      on extensive experience. Many theoretical accounts of behavior in the face of
      uncertainty invoke planning mechanisms that explicitly take uncertainty into
      account. We suggest that the simpler mechanisms of the BG can also contribute to
      the development of behavior under such conditions. We focus on learning under
      conditions in which sensory information takes time to resolve, e.g., when a
      poorly perceived goal stimulus takes non-negligible time to identify. It may be
      advantageous to begin acting quickly under uncertainty--possibly via decisions
      that are suboptimal for the actual goal--rather than to wait for sensory
      information to fully resolve. We present a model of skill acquisition in which
      control is transferred, with experience, from a planning controller (denoted A),
      corresponding to the PFC, to a simpler controller (B), corresponding to the BG.
      We apply our model to a task in which a learning agent must execute a series of
      actions to achieve a goal (selected randomly at each trial from a small set).
      Over the course of a trial, the agent's goal representation evolves from
      representing all possible goals to only the selected goal. A is restricted to
      select movements only when goal representation is fully resolved. Model behavior
      is similar to that observed in humans accomplishing similar tasks. Thus, B can by
      itself account for the development of behavior under an evolving sensory
      representation, suggesting that the BG can contribute to learning and control
      under conditions of uncertainty.

PMID- 19595992
TI  - A model of encoding and decoding in V1 and MT accounts for motion perception
      anisotropies in the human visual system.
AB  - We used the motion aftereffect (MAE) to psychophysically characterize tuning of
      motion perception in the human visual system. The function relating MAE strength
      and the range of directions present in the adapter stimulus provides information
      regarding the width of direction tuning of motion adaptation. We compared the
      directional anisotropy in MAE tuning width to the well-known oblique effect in
      motion direction discrimination. In agreement with previous research, we found
      that subjects had lower motion direction discrimination thresholds for cardinal
      compared to oblique directions. For each subject, we also estimated MAE tuning
      width for a cardinal and an oblique direction by measuring the strength of the
      MAE for adapter stimuli containing different directional variances. The MAE
      tuning width was smaller for the cardinal direction, suggesting a fundamental
      similarity between motion direction discrimination and tuning of the MAE. We
      constructed a model of encoding of motion stimuli by V1 and MT and decoding of
      stimulus information from the cells in area MT. The model includes an anisotropy
      in the representation of different directions of motion in area V1. As a
      consequence of the connections implemented in the model, this anisotropy
      propagates to cells in MT. Model simulations predicted an oblique effect for both
      direction discrimination thresholds and MAE tuning width, consistent with our
      experimental results. The model also concurs with a recent report that the
      magnitude of the oblique effect for direction discrimination is inversely
      proportional to the directional variance of the stimulus. The agreement between
      model predictions and empirical data was obtained only when the model employed a
      maximum likelihood decoding algorithm. Alternative decoding mechanisms such as
      vector averaging and winner-take-all failed to account for the psychophysical
      results.

PMID- 19595994
TI  - Use of X-linked short tandem repeats loci to confirm mutations in parentage
      caseworks.
AB  - BACKGROUND: Analysis of short tandem repeats (STRs) has become wide-spread in
      routine for parentage test. However, the accuracy of STR is sometimes interfered
      by the presence of microsatellite mutations. Analysis of other DNA markers such
      as the HV1 and HV2 hypervariable regions of mitochondrial DNA or the Y-STR
      becomes essential to settle the noncongruence. Owing to the time-consuming nature
      of these tests, we explored here the use of X-chromosome STR (X-STR) to resolve
      the paternity and maternity disputes. METHODS: At first, the autosomal STR
      mutation frequencies among 4758 Taiwanese were analyzed. Population data were
      obtained from randomly selected 99 females and 101 males to setup the X-STR
      database. Two families with a mismatch of one allele in autosomal STR analysis
      were subjected to the X-STR test to explore its clinical application. RESULTS:
      The STR mutations occurred in all 15 autosomal STR loci with the exception of
      TH01 and TPOX. The mutation rates could reach as high as 0.106% for the loci of
      D8S1179 and D18S51. As to the X-STR frequencies, the probability values of exact
      tests for Hardy-Weinberg equilibrium were 0.1471, 0.0019, 0.0025, 0.1427, and
      0.1167 for the loci of DXS7132, DXS981, DXS6789, DXS101, and HPRTB, respectively.
      In addition, 33 and 34 different haplotypes were revealed for DXS101-DXS6789 and
      DXS7132-DXS981, respectively. Furthermore, two cases with one allele mismatch in
      routine parentage test were resolved by performing X-STR analysis. CONCLUSION:
      Typing of X-STR markers is recommended for parentage test when 1 or 2 alleles
      mismatch is present or when the samples are difficult to be analyzed.

PMID- 19595993
TI  - Instructional control of reinforcement learning: a behavioral and
      neurocomputational investigation.
AB  - Humans learn how to behave directly through environmental experience and
      indirectly through rules and instructions. Behavior analytic research has shown
      that instructions can control behavior, even when such behavior leads to sub
      optimal outcomes (Hayes, S. (Ed.). 1989. Rule-governed behavior: cognition,
      contingencies, and instructional control. Plenum Press.). Here we examine the
      control of behavior through instructions in a reinforcement learning task known
      to depend on striatal dopaminergic function. Participants selected between
      probabilistically reinforced stimuli, and were (incorrectly) told that a specific
      stimulus had the highest (or lowest) reinforcement probability. Despite
      experience to the contrary, instructions drove choice behavior. We present neural
      network simulations that capture the interactions between instruction-driven and
      reinforcement-driven behavior via two potential neural circuits: one in which the
      striatum is inaccurately trained by instruction representations coming from
      prefrontal cortex/hippocampus (PFC/HC), and another in which the striatum learns
      the environmentally based reinforcement contingencies, but is "overridden" at
      decision output. Both models capture the core behavioral phenomena but, because
      they differ fundamentally on what is learned, make distinct predictions for
      subsequent behavioral and neuroimaging experiments. Finally, we attempt to
      distinguish between the proposed computational mechanisms governing instructed
      behavior by fitting a series of abstract "Q-learning" and Bayesian models to
      subject data. The best-fitting model supports one of the neural models,
      suggesting the existence of a "confirmation bias" in which the PFC/HC system
      trains the reinforcement system by amplifying outcomes that are consistent with
      instructions while diminishing inconsistent outcomes.

PMID- 19595995
TI  - Effect of methanol and Me2SO exposure on mitochondrial activity and distribution
      in stage III ovarian follicles of zebrafish (Danio rerio).
AB  - In this study the effect of cryoprotectants that have been shown to be the least
      toxic to zebrafish ovarian follicles (methanol and Me(2)SO), on mitochondria of
      stage III ovarian follicles was evaluated. The mitochondrial distributional
      arrangement, mitochondrial membrane potential, mtDNA copy number, ATP levels and
      ADP/ATP ratios were assessed following exposure to cryoprotectants for 30 min at
      room temperature. Results obtained by confocal microscopy showed that 30 min
      exposure to 2M methanol induced a loss of membrane potential, although viability
      tests showed no decrease in survival even after 5h post-exposure incubation.
      Higher concentrations of methanol (3 and 4M) induced not only a decrease in
      mitochondrial membrane potential but also the loss of mitochondrial
      distributional arrangement, which suggested a compromised mitochondrial function.
      Furthermore 3 and 4M treatments resulted in a decrease in viability assessed by
      Fluorescein diacetate-Propidium iodide (FDA-PI) and in a decrease in mtDNA copy
      number and ADP/ATP ratio after 5h incubation following methanol exposure,
      indicating a delayed effect. The use of Me(2)SO, which is considered to be a more
      toxic CPA to zebrafish ovarian follicles than methanol, caused a decrease in
      viability and a sustained decrease in ATP levels accompanied by failure to
      maintain mtDNA copy number within 1h post-exposure incubation. These results
      indicated that even CPAs that are considered to have no toxicity as determined by
      Trypan blue (TB) and FDA-PI tests can have a deleterious effect on mitochondrial
      activity, potentially compromising oocyte growth and embryo development.

PMID- 19595996
TI  - Trypanosoma cruzi SHSP16: Characterization of an alpha-crystallin small heat
      shock protein.
AB  - This report describes the characterization of a member of the alpha-crystallin
      small heat shock protein family in a trypanosomatid, which was isolated from the
      human pathogen Trypanosoma cruzi. One alpha-crystallin small heat shock protein
      gene was identified in a database search. The coding region is located in an open
      reading frame of 429bp encoding a protein of 142 amino acids. The amino acid
      sequence was deduced from the isolated gene. The protein has an alpha-crystallin
      domain characteristic of the alpha-crystallin small heat shock proteins and a
      molecular weight of 15.9kDa, so the protein was designated SHSP16. Analysis of
      the nucleotide sequences of four different T. cruzi strains showed two different
      sequences, which correspond to the two main T. cruzi genetic groups. Gene
      expression analysis by RT-PCR showed increased transcription of the gene after
      the parasite was exposed to heat stress. Recombinant SHSP16 showed molecular
      chaperone activity in vitro, because it inhibited the thermal aggregation of the
      mitochondrial malate dehydrogenase enzyme.

PMID- 19595997
TI  - Bag-1M inhibits the transactivation of the glucocorticoid receptor via
      recruitment of corepressors.
AB  - The Bcl-2 associated athanogene 1M (Bag-1M) is known to repress the
      transactivation of the glucocorticoid receptor (GR). We report here that Bag-1M
      inhibits the action of GR via recruitment of corepressors, including nuclear
      receptor corepressor (NcoR) and silencing mediator for retinoic acid and thyroid
      hormone receptor (SMRT), and histone deacetylase (HDAC)3 to the genomic response
      element of a glucocorticoid-regulated human metallothionein IIa (hMTIIa) gene. A
      mutant GR lacking the interaction with BAG-1M fails to recruit the corepressors
      NcoR and SMRT. RNAi-mediated knock down of corepressors and the use of HDAC
      inhibitor relieved Bag-1M-induced repression on the transactivation of the GR. In
      addition, Bag-1M is not involved in the degradation of the receptor. These
      findings indicate a novel mechanism by which Bag-1M acts as a corepressor and
      downregulates the activity of the GR.

PMID- 19595999
TI  - "Native-like aggregation" of the acylphosphatase from Sulfolobus solfataricus and
      its biological implications.
AB  - Studies in vitro show that globular proteins can experience the formation of
      native-like conformational states able to self-assemble with no need of
      transitions across the energy barrier for unfolding, and that such processes can
      lead eventually to the formation of amyloid-like species. Circumstantial evidence
      collected in vivo suggests that aggregation of native-like states can be a
      concrete possibility for living organisms and thus more relevant than previously
      thought. In this review we summarize the key observations collected on the
      "native-like aggregation" of the acylphosphatase from Sulfolobus solfataricus, a
      protein that has allowed the direct monitoring and analysis of native-like
      aggregates for its propensity to form rapidly native-like aggregates and their
      slow conversion into amyloid-like aggregates.

PMID- 19595998
TI  - Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia.
AB  - Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to
      therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies
      to endogenous FVIII in individuals with acquired hemophilia. We have described
      FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in
      acquired hemophilia patients. Here, we compared the properties of proteolytic
      auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly
      between the two groups of antibodies. Proline-phenylalanine-arginine
      methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing
      autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG
      in acquired hemophilia patients are different from that of inhibitor-positive
      hemophilia A patients.

PMID- 19596000
TI  - Influenza A virus-induced caspase-3 cleaves the histone deacetylase 6 in infected
      epithelial cells.
AB  - Histone deacetylase 6 (HDAC6) is a multi-substrate cytoplasmic enzyme that
      regulates many important biological processes. Recently, some reports have
      implicated HDAC6 in viral infection. However, nothing is known about its
      regulation in virus-infected cells. The data presented here for the first time
      demonstrate the caspase-3-mediated cleavage of HDAC6 in influenza A virus (IAV)
      infected cells. HDAC6 polypeptide contains the caspase-3 cleavage motif DMAD-S at
      the C-terminus, and is a caspase-3 substrate. The cleavage removes most of the C
      terminal ubiquitin-binding zinc finger domain from HDAC6, which could be
      significant for HDAC6's role in IAV-induced apoptosis in infected cells.

PMID- 19596001
TI  - Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis
      via alterations in apoptotic pathways and JNK signaling.
AB  - Hypothermia is the most effective means of protecting the brain, heart and other
      organs during ischemia/reperfusion (I/R) injury. However, the precise mechanisms
      for hypothermia to inhibit I/R-induced endothelial cell apoptosis are not fully
      understood. In the present study, human umbilical endothelial cells (HUVECs) were
      exposed to ischemia followed by reperfusion under normothermia (37 degrees C) or
      hypothermia (33 degrees C). Our results showed that hypothermia markedly reduced
      I/R-induced endothelial cell apoptosis, the expression of cleaved caspase-3 and
      PARP. Moreover, hypothermia markedly reversed I/R-induced activation of
      Fas/caspase-8, the increase of Bax and decrease of Bcl-2. Furthermore,
      hypothermia inhibited JNK1/2 activation via MKP-1 induction. Together, these data
      demonstrate that hypothermia represses I/R-induced endothelial cell apoptosis by
      inhibiting both extrinsic- and intrinsic-dependent apoptotic pathways and
      activation of JNK1/2.

PMID- 19596002
TI  - Supramolecular organization of phycobiliproteins in the chlorophyll d-containing
      cyanobacterium Acaryochloris marina.
AB  - Here we report the high-resolution detail of the organization of phycobiliprotein
      structures associated with photosynthetic membranes of the chlorophyll d
      containing cyanobacterium Acaryochloris marina. Cryo-electron transmission
      microscopy on native cell sections show extensive patches of near-crystalline
      phycobiliprotein rods that are associated with the stromal side of photosynthetic
      membranes. This supramolecular photosynthetic structure represents a novel
      mechanism of organizing the photosynthetic light-harvesting machinery. In
      addition, the specific location of phycobiliprotein patches suggests a physical
      separation of photosystem I and photosystem II reaction centres. Based on this
      finding and the known photosystem's structure in Acaryochloris, we discuss
      possible membrane arrangements of photosynthetic membrane complexes in this
      species.

PMID- 19596003
TI  - Adiponectin promotes migration activities of endothelial progenitor cells via
      Cdc42/Rac1.
AB  - Adiponectin has anti-atherosclerotic effects through its direct actions on
      vascular cells. The present study investigates the molecular mechanisms of
      adiponectin in the migration of endothelial progenitor cells (EPCs) which play an
      important role in neovascularization and re-endothelization. The phosphorylation
      of Akt and the activations of Cdc42 and Rac1 were significantly increased by
      adiponectin. Adiponectin increased the migration activity of EPCs, which was
      completely inhibited by a PI3-kinase inhibitor. siRNA of Cdc42 or Rac1 completely
      inhibited the adiponectin-induced migration, but siRNA of Akt had no effects,
      indicating that adiponectin promotes the migration activities of EPCs mainly
      through PI3-kinase/Cdc42/Rac1.

PMID- 19596004
TI  - Differential effects of chronic, in vivo, PPAR's stimulation on the myocardial
      subcellular redistribution of FAT/CD36 and FABPpm.
AB  - This study reveals that the activation of either PPARalpha (WY 14643) or PPARbeta
      (GW0742) each induce the translocation of FAT/CD36 from an intracellular pool(s)
      to the plasma membrane, while PPARbeta also induces the subcellular
      redistribution of FABPpm(Got2) to the plasma membrane. In contrast, activation of
      PPARgamma failed to induce the subcellular redistribution of FAT/CD36 and FABPpm.
      These PPARalpha-, and PPARbeta-induced changes in the plasmalemmal content of
      these fatty acid transporters were associated with the concurrent upregulation of
      fatty acid triacylglycerol esterification (PPARbeta) and oxidation (PPARalpha and
      PPARbeta). Observed effects of chronic PPAR stimulation were not related to
      either AMPK or ERK1/2 activation.

PMID- 19596006
TI  - Structure-activity relationship of amyloid fibrils.
AB  - Protein aggregation is a process in which proteins self-associate into
      imperfectly ordered macroscopic entities. Such aggregates are generally
      classified as either amorphous or highly ordered, the most common form of the
      latter being amyloid fibrils. Amyloid fibrils composed of cross-beta-sheet
      structure are the pathological hallmarks of several diseases including
      Alzheimer's disease, but are also associated with functional states such as the
      fungal HET-s prion. This review aims to summarize the recent high-resolution
      structural studies of amyloid fibrils in light of their (potential) activities.
      We propose that the repetitive nature of the cross-beta-sheet structure of
      amyloids is key for their multiple properties: the repeating motifs can translate
      a rather non-specific interaction into a specific one through cooperativity.

PMID- 19596005
TI  - Touch induces ATP release in Arabidopsis roots that is modulated by the
      heterotrimeric G-protein complex.
AB  - Amongst the many stimuli orienting the growth of plant roots, of critical
      importance are the touch signals generated as roots explore the mechanically
      complex soil environment. However, the molecular mechanisms behind these sensory
      events remain poorly defined. We report an impaired obstacle-avoiding response of
      roots in Arabidopsis lacking a heterotrimeric G-protein. Obstacle avoidance may
      utilize a touch-induced release of ATP to the extracellular space. While
      sequential touch stimulation revealed a strong refractory period for ATP release
      in response to mechano-stimulation in wild-type plants, the refractory period in
      mutants was attenuated, resulting in extracellular ATP accumulation. We propose
      that ATP acts as an extracellular signal released by mechano-stimulation and that
      the G-protein complex is needed for fine-tuning this response.

PMID- 19596007
TI  - The antifungal plant defensin RsAFP2 from radish induces apoptosis in a
      metacaspase independent way in Candida albicans.
AB  - We show that the antifungal plant defensin Raphanus sativus antifungal protein 2
      (RsAFP2) from radish induces apoptosis and concomitantly triggers activation of
      caspases or caspase-like proteases in the human pathogen Candida albicans.
      Furthermore, we demonstrate that deletion of C. albicans metacaspase 1, encoding
      the only reported (putative) caspase in C. albicans, significantly affects
      caspase activation by the apoptotic stimulus acetic acid, but not by RsAFP2. To
      our knowledge, this is the first report on the induction of apoptosis with
      concomitant caspase activation by a defensin in this pathogen. Moreover, our data
      point to the existence of at least two different types of caspases or caspase
      like proteases in C. albicans.

PMID- 19596008
TI  - Negligible contribution of bone marrow-derived cells to collagen production
      during hepatic fibrogenesis in mice.
AB  - BACKGROUND & AIMS: Recent studies have reported that bone marrow (BM)-derived
      cells migrating into fibrotic liver tissue exhibit a myofibroblast-like phenotype
      and may participate in the progression of liver fibrosis. However, their
      contribution to collagen production has not been fully verified yet. We revisited
      this issue by using 2 mechanistically distinct liver fibrosis models introduced
      into transgenic collagen reporter mice and their BM recipients. METHODS: BM of
      wild-type mice was replaced by cells obtained from transgenic animals harboring
      tissue-specific enhancer/promoter sequences of alpha2(I) collagen gene (COL1A2)
      linked to enhanced green fluorescent protein (EGFP) or firefly luciferase (LUC)
      gene. Liver fibrosis was introduced into those mice by repeated carbon
      tetrachloride injections or ligation of the common bile duct. Activation of
      COL1A2 promoter was assessed by confocal microscopic examination detecting EGFP
      signals and luciferase assays of liver homogenates. RESULTS: The tissue-specific
      COL1A2 enhancer/promoter was activated in hepatic stellate cells following a
      single carbon tetrachloride injection or during primary culture on plastic. A
      large number of EGFP-positive collagen-expressing cells were observed in liver
      tissue of transgenic COL1A2/EGFP mice in both liver fibrosis models. In contrast,
      there were few EGFP-positive BM-derived collagen-producing cells detected in
      fibrotic liver tissue of COL1A2/EGFP recipients. Luciferase assays of liver
      tissues from COL1A2/LUC-recipient mice further indicated that BM-derived cells
      produced little collagen in response to fibrogenic stimuli. CONCLUSIONS: By using
      a specific and sensitive experimental system, which detects exclusively BM
      derived collagen-producing cells, we conclude an unexpectedly limited role of BM
      derived cells in collagen production during hepatic fibrogenesis.

PMID- 19596010
TI  - Multicenter, randomized, placebo-controlled trial of amitriptyline in children
      with functional gastrointestinal disorders.
AB  - BACKGROUND & AIMS: There are no prospective, multicenter, double-blind, placebo
      controlled, randomized pharmacologic trials for the treatment of pain-predominant
      functional gastrointestinal disorders in children. The aim of this study was to
      evaluate the efficacy of amitriptyline in children with pain-predominant
      functional gastrointestinal disorders. METHODS: In this multicenter placebo
      controlled trial, children with irritable bowel syndrome, functional abdominal
      pain, or functional dyspepsia were randomized to 4 weeks of placebo or
      amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of
      gastrointestinal symptoms, psychological traits, and daily activities occurred
      before and after intervention. Pain was assessed daily with self-report diaries.
      The primary outcome was overall response to treatment (child's assessment of pain
      relief and sense of improvement). Secondary outcomes were effect on psychosocial
      traits and daily functioning. RESULTS: Ninety children were enrolled, and 83
      completed the study (placebo, 40 children [30 girls]; drug, 43 children [35
      girls]). A total of 63% of patients reported feeling better and 5% feeling worse
      in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling
      worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in
      38% of children receiving placebo compared with excellent in 15% and good in 35%
      of children treated with amitriptyline (P = .85). Logistic regression analysis of
      those reporting excellent or good response versus fair, poor, or failed response
      showed no difference between amitriptyline and placebo (P = .83). Children who
      had more severe pain at baseline in both groups (P = .0065) had worse outcome.
      Amitriptyline reduced anxiety scores (P < .0001). CONCLUSIONS: Both amitriptyline
      and placebo were associated with excellent therapeutic response. There was no
      significant difference between amitriptyline and placebo after 4 weeks of
      treatment. Patients with mild to moderate intensity of pain responded better to
      treatment.

PMID- 19596009
TI  - Biology and treatment of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is a recently recognized but expanding disorder
      characterized by antigen-driven eosinophil accumulation in the esophagus.
      Symptoms frequently mimic those of gastroesophageal reflux disease, but the
      diseases are distinct in their histopathology, gene expression signature,
      response to therapy, hereditary risk, and association with allergies. The
      pathogenesis of eosinophilic esophagitis involves environmental and genetic
      factors, particularly food antigens and expression level of the eosinophil
      chemoattractant eotaxin-3, respectively. Analyses of gene expression signatures
      and animal models have indicated the importance of adaptive T-cell immunity that
      involves interleukin-5 and interleukin-13-induced esophageal epithelial cell
      responses. Symptoms, dysregulation of esophageal gene expression, and pathology
      are largely reversible following reduced exposure to specific food antigens as
      well as anti-inflammatory therapy, but chronic treatment is necessary to prevent
      relapse. Therefore, eosinophilic esophagitis is a disease with unique features
      that include chronic esophagitis, atopy, immune sensitization to oral antigens,
      reversibility, and familial association.

PMID- 19596012
TI  - Activation of human enteric neurons by supernatants of colonic biopsy specimens
      from patients with irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Pathological features in irritable bowel syndrome (IBS)
      include alterations in mucosal cell content and mediator release that might alter
      signaling to nearby submucosal neurons. METHODS: Voltage sensitive dye imaging
      was used to record the effects of mediators, released from mucosal biopsies of
      IBS patients, on cell bodies of 1207 submucosal neurons from 76 human colonic
      tissue specimens. Supernatants, containing these mediators, were collected
      following incubation with colonic mucosal biopsies from 7 patients with diarrhea
      predominant IBS (D-IBS), 4 with constipation-predominant IBS (C-IBS), and 4
      healthy controls. Serotonin, histamine and tryptase concentrations in
      supernatants and lamina propria mast cell density were determined. RESULTS: In
      contrast to controls, IBS supernatants significantly increased the rate of spike
      discharge in 58% of human submucosal neurons. Neurons that responded to IBS
      supernatant had a median spike frequency of 2.4 Hz compared to 0 Hz for control
      supernatants. Supernatants from C-IBS and D-IBS evoked similar spike discharge.
      The activation induced by IBS supernatants was inhibited by histamine receptor
      (H1-H3) antagonists, 5-HT3 receptor antagonist, and protease inhibition.
      Serotonin, histamine and tryptase levels in supernatants correlated with the
      spike discharge induced by the supernatants. Mast cells density as well as
      histamine and tryptase levels in supernatants were higher in IBS than in
      controls. CONCLUSIONS: Mediators released from mucosal biopsies of IBS patients
      can activate human submucosal neurons. The activation required histamine,
      serotonin and proteases but was not associated with IBS subtype. Altered
      signaling between mucosa and the enteric nervous system might be involved in IBS
      pathogenesis.

PMID- 19596011
TI  - Toll-like receptor 4-mediated regulation of spontaneous Helicobacter-dependent
      colitis in IL-10-deficient mice.
AB  - BACKGROUND & AIMS: The commensal microbiota is believed to have an important role
      in regulating immune responsiveness and preventing intestinal inflammation.
      Intestinal microbes produce signals that regulate inflammation via Toll-like
      receptor (TLR) signaling, but the mechanisms of this process are poorly
      understood. We investigated the role of the anti-inflammatory cytokine
      interleukin (IL)-10 in this signaling pathway using a mouse model of colitis.
      METHODS: Clinical, histopathologic, and functional parameters of intestinal
      inflammation were evaluated in TLR4(-/-), IL-10(-/-), and TLR4(-/-) x IL-10(-/-)
      mice that were free of specific pathogens and in TLR4(-/-) x IL-10(-/-) mice
      following eradication and reintroduction of Helicobacter hepaticus. Regulatory T
      cell (Treg) function was evaluated by crossing each of the lines with transgenic
      mice that express green fluorescent protein under control of the endogenous
      regulatory elements of Foxp3. Apoptotic cells in the colonic lamina propria were
      detected by a TUNEL assay. RESULTS: TLR4-mediated signals have 2 interrelated
      roles in promoting inflammation in TLR4(-/-) x IL-10(-/-) mice. In the absence of
      TLR4-mediated signals, secretion of proinflammatory and immunoregulatory
      cytokines is dysregulated. Tregs (Foxp3(+)) that secrete interferon-gamma and IL
      17 accumulate in the colonic lamina propria of TLR4(-/-) x IL-10(-/-) mice and do
      not prevent inflammation. Aberrant control of epithelial cell turnover results in
      the persistence of antigen-presenting cells that contain apoptotic epithelial
      fragments in the colonic lamina propria of Helicobacter-infected TLR4(-/-) mice.
      CONCLUSIONS: In mice that lack both IL-10- and TLR4-mediated signals, aberrant
      regulatory T-cell function and dysregulated control of epithelial homeostasis
      combine to exacerbate intestinal inflammation.

PMID- 19596013
TI  - FOXP3 expression in hepatitis C virus-specific CD4+ T cells during acute
      hepatitis C.
AB  - BACKGROUND & AIMS: Down-regulation of hepatitis C virus (HCV)-specific CD4(+) T
      cell responses is a hallmark of chronic viral persistence in acute hepatitis C.
      FOXP3(+)CD25(+)CD4(+) regulatory T cells can modulate HCV-specific immune
      responses in vitro, but the role of virus-specific regulatory T cells in the
      pathogenesis of chronic viral persistence is unknown. METHODS: Two novel HLA-DR15
      tetramers were synthesized to study the kinetics and phenotype of FOXP3(+)
      expressing HCV-specific CD4(+) T cells from 10 patients with acute hepatitis C
      and 15 patients with chronic hepatitis C. RESULTS: In acute hepatitis C,
      generally only a low percentage of HCV-specific CD4(+) T cells expressed FOXP3(+)
      (mean of 2.5% in patients with self-limited acute hepatitis C vs 2.4% in patients
      with evolving chronic hepatitis C). Although distinct but short-lived increases
      in virus-specific FOXP3(+)CD4(+) T cells occurred in 3 patients (30%, 26%, and 7%
      of tet(+) CD4(+) T cells, respectively), these did not correlate with the
      evolution of chronic hepatitis C. HCV-specific FOXP3(+)CD4(+) T cells displayed a
      distinct phenotype, with only 10% expressing CD25 and 40% being CD127low.
      Interestingly, this phenotype of FOXP3(+)CD4(+) T cells was already expanded in
      bulk CD4(+) T cells in patients with chronic hepatitis C. CONCLUSIONS: Although
      short-lived increases in HCV-specific FOXP3(+)CD4(+) T cells occur during the
      course of acute hepatitis C, we could not demonstrate an association of HCV
      specific regulatory T cells and persistent viremia.

PMID- 19596014
TI  - Colectomy rate comparison after treatment of ulcerative colitis with placebo or
      infliximab.
AB  - BACKGROUND & AIMS: The efficacy of infliximab for treating patients with
      ulcerative colitis has been established. METHODS: The Active Ulcerative Colitis
      Trial (ACT)-1 and ACT-2 randomized, double-blind, placebo-controlled studies
      evaluated infliximab induction and maintenance therapy in moderately to severely
      active ulcerative colitis. Overall, 728 patients received placebo or infliximab
      (5 or 10 mg/kg) intravenously at weeks 0, 2, and 6, then every 8 weeks through
      week 46 (ACT-1) or 22 (ACT-2). Colectomy, hospitalization, and surgery/procedure
      data through 54 weeks after the first infusion were obtained from ACT-1, ACT-2,
      and associated data sources. In the prespecified analysis, all data were combined
      to ascertain time to colectomy. Kaplan-Meier product-limit method was used to
      estimate the cumulative incidence of colectomy, and log-rank test was used to
      compare the combined infliximab group and placebo. RESULTS: Eighty-seven percent
      (630 of 728) of patients had complete colectomy follow-up; 13% (98 of 728) of
      patients had a median follow-up of 6.2 months. The cumulative incidence of
      colectomy through 54 weeks was 10% for infliximab and 17% for placebo (P = .02),
      yielding an absolute risk reduction of 7%. Compared with placebo, fewer
      ulcerative colitis-related hospitalizations and surgeries/procedures per 100
      patient-years of treatment occurred with infliximab therapy: 40 vs 20 (P = .003)
      and 34 vs 21 (P = .03), respectively. Serious adverse events occurring in
      infliximab-treated patients included serious infections, tuberculosis,
      histoplasmosis, listeriosis, and malignancy. CONCLUSIONS: Patients with
      moderately to severely active ulcerative colitis treated with infliximab were
      less likely to undergo colectomy through 54 weeks than those receiving placebo.

PMID- 19596015
TI  - Transcriptional profiles of adult male and female Schistosoma japonicum in
      response to insulin reveal increased expression of genes involved in growth and
      development.
AB  - Microarray analysis was used to investigate differential gene regulation in adult
      male and female Schistosoma japonicum cultured in the presence or absence of
      insulin in vitro. A total of 1,101 genes were up- or down-regulated in response
      to insulin, the majority of differential expression occurring 24h after the
      addition of insulin to the cultures. Genes differentially expressed in male or
      female worms were predominantly involved in growth and development, with
      significant sex-specific differences in transcriptional profiles evident. Insulin
      appeared to promote protein synthesis and control protein degradation more
      prominently in male parasites. The study also indicated that insulin plays a more
      pronounced role in the uptake of glucose in unpaired female parasites, as
      reflected in the increased stimulation of gene expression of the
      phosphatidylinositol 3-kinase sub-pathway of insulin signalling. Insulin may also
      impact on the sexual differentiation and fecundity of female schistosomes by
      activation of the mitogenic-activated protein kinase sub-pathway.

PMID- 19596016
TI  - Crystal structure of the TNF-alpha-Inducing protein (Tipalpha) from Helicobacter
      pylori: Insights into Its DNA-binding activity.
AB  - Helicobacter pylori infection is one of the highest risk factors for
      gastroduodenal diseases including gastric cancer. Tumor necrosis factor-alpha
      (TNF-alpha) is one of the essential cytokines for tumor promotion, and thus, an
      H. pylori protein that induces TNF-alpha is believed to play a significant role
      in gastric cancer development in humans. The HP0596 gene product of H. pylori
      strain 26695 was identified as the TNF-alpha-inducing protein (Tipalpha).
      Tipalpha is secreted from H. pylori as dimers and enters the gastric cells. It
      was shown to have a DNA-binding activity. Here, we have determined the crystal
      structure of Tipalpha from H. pylori. Its monomer consists of two structural
      domains ("mixed domain" and "helical domain"). Tipalpha exists as a dimer in the
      crystal, and the dimeric structure represents a novel scaffold for DNA binding. A
      positively charged surface patch formed across the two monomers of the Tipalpha
      dimer by the loop between helices alpha1 and alpha2 may be important in DNA
      binding.

PMID- 19596017
TI  - Morphine-induced conditioned place preference in rats is inhibited by
      electroacupuncture at 2 Hz: role of enkephalin in the nucleus accumbens.
AB  - Our previous studies have demonstrated that morphine-induced conditioned place
      preference (CPP) can be inhibited by 2 Hz electroacupuncture (EA). This
      inhibition can be blocked by either the opioid receptor antagonist naloxone
      (i.p.) or lesion in the nucleus accumbens (NAc), providing evidence that
      endogenous opioid system in the NAc mediates the effects of EA. Here we report
      that 1) A single session of 2 Hz EA produced a significant increase of the
      content of enkephalin in the NAc of morphine-induced CPP rats, and this effect
      was stronger in three consecutive sessions of EA; 2) Intracerebroventricular
      injection of the mu-opioid receptor antagonist CTAP or delta-opioid receptor
      antagonist NTI, but not kappa-opioid receptor antagonist nor-BNI, dose
      dependently reversed the inhibitory effects of 2 Hz EA on the expression of
      morphine-induced CPP; 3) Three consecutive sessions of 2 Hz EA up-regulated the
      mRNA level of preproenkephalin in the NAc of morphine-induced CPP rats. The
      results suggest that the inhibitory effects of 2 Hz EA on the expression of the
      morphine CPP is mediated by mu- and delta-, but not kappa-opioid receptor,
      possibly via accelerating both the release and synthesis of enkephalin in the
      NAc. These findings support the possibility of using 2 Hz EA for the treatment of
      opiate addiction.

PMID- 19596018
TI  - Orexin receptor antagonism prevents transcriptional and behavioral plasticity
      resulting from stimulant exposure.
AB  - Orexin is a key neurotransmitter of central arousal and reward circuits in the
      CNS. Two receptors respond to orexin signaling, Orexin 1 Receptor (OX1R) and
      Orexin 2 Receptor (OX2R) with partially overlapping brain distributions. Genetic
      and pharmacological studies suggest orexin receptor antagonists could provide
      therapeutic benefit for insomnia and other disorders in which sleep/wake cycles
      are disrupted. Preclinical data has also emerged showing that the orexin system
      is involved in the behavioral and neurological effects of drugs of abuse (Aston
      Jones et al., 2009; Harris et al., 2005). Here we report sleep promoting effects
      of a recently described small molecule dual orexin receptor OX1R and OX2R
      antagonist. This dual orexin receptor antagonist (DORA) also inhibits the ability
      of subchronic amphetamine to produce behavioral sensitization measured 10 days
      following pre-treatment. Transcriptional profiling of isolated reward and arousal
      circuits from brains of behaviorally sensitized animals showed that the DORA
      blocked the significant alteration of gene expression levels in response to
      amphetamine exposure, particularly those associated with synaptic plasticity in
      the VTA. Further, DORA attenuates the ability of nicotine to induce reinstatement
      of extinguished responding for a reinforcer, demonstrating selectivity of the
      effect to reward pathways and not to food intake. In summary, these data
      demonstrate efficacy of a dual orexin receptor antagonist for promotion of sleep
      and suggest that pharmacological inhibition of the orexin system may play a role
      in both prevention of drug-induced plasticity and drug-relapse.

PMID- 19596019
TI  - Reduced emotional and corticosterone responses to stress in mu-opioid receptor
      knockout mice.
AB  - The detailed mechanisms of emotional modulation in the nervous system by opioids
      remain to be elucidated, although the opioid system is well known to play
      important roles in the mechanisms of analgesia and drug dependence. In the
      present study, we conducted behavioral tests of anxiety and depression and
      measured corticosterone concentrations in both male and female mu-opioid receptor
      knockout (MOP-KO) mice to reveal the involvement of mu-opioid receptors in stress
      induced emotional responses. MOP-KO mice entered more and spent more time in the
      open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice
      also displayed significantly decreased immobility in a 15 min tail-suspension
      test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly
      decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted
      for 5 consecutive days. The increase in plasma corticosterone concentration
      induced by tail-suspension, repeated forced swim, or restraint stress was reduced
      in MOP-KO mice compared with wild-type mice. Corticosterone levels were not
      different between wild-type and MOP-KO mice before stress exposure. In contrast,
      although female mice tended to exhibit fewer anxiety-like responses in the tail
      suspension test in both genotypes, no significant gender differences were
      observed in stress-induced emotional responses. These results suggest that MOPs
      play an important facilitatory role in emotional responses to stress, including
      anxiety- and depression-like behavior and corticosterone levels.

PMID- 19596021
TI  - Cerebral representation of non-verbal emotional perception: fMRI reveals
      audiovisual integration area between voice- and face-sensitive regions in the
      superior temporal sulcus.
AB  - Successful social interaction relies on multimodal integration of non-verbal
      emotional signals. The neural correlates of this function, along with those
      underlying the processing of human faces and voices, have been linked to the
      superior temporal sulcus (STS) in previous neuroimaging studies. Yet, recently it
      has been demonstrated that this structure consists of several anatomically
      defined sections, including a trunk section as well as two separate terminal
      branches, and exhibits a pronounced spatial variability across subjects. Using
      functional magnetic resonance imaging (fMRI), we demonstrated that the neural
      representations of the audiovisual integration of non-verbal emotional signals,
      voice sensitivity and face sensitivity are located in different parts of the STS
      with maximum voice sensitivity in the trunk section and maximum face sensitivity
      in the posterior terminal ascending branch. The audiovisual integration area for
      emotional signals is located at the bifurcation of the STS at an overlap of voice
      and face-sensitive regions. In summary, our findings evidence a functional
      subdivision of the STS into modules subserving the processing of different
      aspects of social communication, here exemplified in human voices and faces and
      audiovisual integration of emotional signals from these sources and suggest a
      possible interaction of the underlying voice- and face-sensitive neuronal
      populations during the formation of the audiovisual emotional percept.

PMID- 19596020
TI  - Oxytocin and/or steroid hormone binding globulin infused into the ventral
      tegmental area modulates progestogen-mediated lordosis.
AB  - Estradiol (E(2)) and progesterone (P(4)) have classical, steroid receptor
      mediated actions in the ventral medial hypothalamus to initiate lordosis of
      female rodents. P(4) and the P(4) metabolite and neurosteroid, 5 alpha-pregnan-3
      alpha-ol-20-one (3 alpha,5 alpha-THP), have non-classical actions in the midbrain
      ventral tegmental area (VTA) to modulate lordosis. We investigated the role of
      steroid hormone binding globulin (SHBG) and oxytocin in the VTA as mechanisms for
      these effects. Rats were ovariectomized and surgically implanted with bilateral
      guide cannulae aimed at the VTA. Rats were E(2)-primed (10 microg/0.2 ml) at hour
      0, and administered 100 (Experiments 1 and 2), 500 (Experiment 3), or 0
      (Experiment 1 and 4) microg/0.2 ml P(4) at hour 44. At hour 47.5, rats received
      bilateral infusions to the VTA, and were tested for lordosis 30 min post
      infusion. Experiment 1: rats were infused with sterile saline vehicle or SHBG
      (4.5 pg/microl) to the VTA. SHBG, compared to vehicle, to the midbrain VTA
      significantly increased lordosis in E(2)- and P(4)-primed, but not E(2)-primed,
      rats. Experiment 2: rats were infused with bilateral infusions of sterile saline
      or oxytocin (1.0 pg/microl). Compared to vehicle, oxytocin to the VTA increased
      lordosis. Experiment 3: rats were administered bilateral intra-VTA infusions of
      saline or an oxytocin receptor antagonist, d(CH(2))(5),[TYr(ME)(2),Thr(4),Tyr
      NH(9,2)] (1.2 pg/microl). Compared to vehicle, the oxytocin receptor antagonist
      to the VTA attenuated lordosis of E(2)- and P(4)-primed rats. Experiment 4: rats
      were E(2)-primed and infused with vehicle, oxytocin, or oxytocin antagonist.
      There were no effects of these manipulations in E(2)-primed rats. Thus, SHBG
      and/or oxytocin may have actions in the VTA for progestogen-facilitated lordosis.

PMID- 19596023
TI  - Retention and degradation of the cyanobacterial toxin cylindrospermopsin in
      sediments - the role of sediment preconditioning and DOM composition.
AB  - Recent results show that cylindrospermopsin is more frequent and widespread in
      surface waters than previously assumed. Studies on the fate of CYN in sediments
      are lacking, but this is important if these resources are used for drinking-water
      production via sediment passage. Therefore, the aim of our study was to determine
      a) CYN retention in two sandy sediments as a function of flow rate, CYN
      concentration, the presence of DOM and the content of fines (1% and 4%,
      respectively) and b) the influence of sediment preconditioning and DOM
      composition of the water (aquatic DOM versus DOM released from lysed cells) on
      CYN degradation. Retention of CYN proved negligible under the investigated
      conditions. Degradation in virgin sediments showed the highest lag phases (20
      days). Preconditioned sediments showed no lag phase. The presence of aquatic DOM
      yielded highest degradation rates (kappa(1)=0.46 and 0.49 day(-1)) without a lag
      phase. Readily available organic carbon sources were preferentially metabolized
      and hence induced a lag phase. Thus, the presence and composition of DOM in the
      water proved important for both CYN degradation rates in preconditioned sediments
      and for the lag phase. Cylindrospermopsin degradation took place solely in the
      sediment and not in the water body.

PMID- 19596022
TI  - Association of genetic polymorphisms in GADD45A, MDM2, and p14 ARF with the risk
      of chronic benzene poisoning in a Chinese occupational population.
AB  - Benzene reactive metabolites can lead to DNA damage and trigger the p53-dependent
      defense responses to maintain genomic stability. We hypothesized that the p53
      dependent genes may play a role in the development of chronic benzene poisoning
      (CBP). In a case-control study of 303 patients with benzene poisoning and 295
      workers occupationally exposed to benzene in south China, we investigated
      associations between the risk of CBP and polymorphisms in three p53-dependent
      genes. Potential interactions of these polymorphisms with lifestyle factors were
      also explored. We found p14(ARF) rs3731245 polymorphism was associated with risk
      of CBP (P=0.014). Compared with those carrying the GG genotype, individuals
      carrying p14(ARF) rs3731245 GA+AA genotypes had a reduced risk of CBP ([adjusted
      odds ratio (OR(adj))=0.57, 95%CI=0.36-0.89]. Further analysis showed p14(ARF)
      TGA/TAG diplotype was associated with an increased risk of CBP (P=0.0006),
      whereas p14(ARF) TGG/TAA diplotype was associated with a decreased risk of CBP
      (P=0.0000001). In addition, we found individuals carrying both MDM2 Del1518 WW
      genotype and p14(ARF) rs3731245 GA+AA genotypes had a lower risk of CBP
      (OR(adj)=0.25; 95%CI=0.10-0.62; P=0.003). Although these results require
      confirmation and extension, our findings suggest that genetic polymorphisms in
      p14(ARF) may have an impact on the risk of CBP in the study population.

PMID- 19596024
TI  - First report on toxins in the Panamanian toads Atelopus limosus, A. glyphus and
      A. certus.
AB  - Major toxins from skin extracts of 18 specimens of six Atelopus toad species
      collected in Panama were analyzed. Chiriquitoxin was identified using (1)H NMR in
      A. limosus and A. glyphus for the first time. Zetekitoxin in A. zeteki and
      tetrodotoxin in A. varius, A. chiriquiensis and A. zeteki were identified again.
      Furthermore, A. certus was suggested to contain a water-soluble toxin other than
      tetrodotoxin.

PMID- 19596026
TI  - The neuroendocrinology of the social brain.

PMID- 19596025
TI  - Observer's control of the moving stimulus increases the flash-lag effect.
AB  - The flash-lag effect (FLE) consists in perceiving a briefly presented stationary
      stimulus to lag behind an aligned moving stimulus. This study investigates the
      effects of actively controlling the moving stimulus. By means of a robotic arm,
      observers continuously moved a dot along a circular trajectory, and a flash was
      displayed closely at unpredictable times. In two experiments, we found that the
      FLE was larger when participants controlled the moving stimulus, compared to a
      computer-controlled condition. Two control conditions tested the possibility that
      the observed modulation of the FLE was due to visuo-spatial attention or dual
      task factors. This study provides evidence that the motor system interacts with
      and possibly speeds up the processing of a moving visual stimulus when the
      observer controls its movement.

PMID- 19596027
TI  - Minimum Overlap Component Analysis (MOCA) of EEG/MEG data for more than two
      sources.
AB  - In many situations various methods to analyze EEG/MEG data result in subspaces of
      the sensor space spanned by potentials of a set of sources. We propose a general
      model free method to decompose such a subspace into contributions from distinct
      sources. This unique decomposition can be achieved by first finding the
      respective subspace in source space using a linear inverse method and then
      finding the linear transformation such that the source distributions are mutually
      orthogonal and have a minimum overlap. The corresponding algorithm is a
      generalization of the recently presented 'Minimum Overlap Component Analysis'
      (MOCA) to more than two sources. The computational cost is negligible and the
      algorithm is almost never trapped in local minima. The method is illustrated with
      results for alpha rhythm.

PMID- 19596029
TI  - Nerve growth factor synthesis in human vascular smooth muscle cells and its
      regulation by dexamethasone.
AB  - BACKGROUND: Neurotrophins are involved in inflammatory pathways influencing
      several cells in healthy states and in diseases such as bronchial asthma. Recent
      studies have shown that nerve growth factor (NGF) is expressed in various non
      neuronal cells. Furthermore, little is known about the different origins and
      regulation of NGF. In the present study, the expression of NGF and its regulation
      by dexamethasone was investigated in cultured human smooth muscle cells derived
      from umbilical veins (HSMC) and human iliacal arteries (HISMC). METHODS: Vascular
      smooth muscle cells were prepared. The presence of NGF was demonstrated by APAAP
      staining, western blotting, ELISA, and reverse transcription polymerase chain
      reaction. Vascular smooth muscle cells were incubated with dexamethasone, and
      cells and supernatants were collected for the measurement of NGF. RESULTS:
      Vascular smooth muscle cells demonstrate mRNA for NGF. Proteins were detectable
      by western blot, ELISA, and APAAP staining. NGF Protein and mRNA were suppressed
      after incubation with dexamethasone (0.1 microM) for 48 h in the vascular smooth
      muscle cells. NGF protein was also detected in cell supernatant and was
      suppressed by dexamethasone as well. CONCLUSION: These data indicate that
      vascular smooth muscle cells are a source of circulating NGF and thus may be
      involved in inflammatory responses mediated by neurotrophins. The suppression of
      NGF synthesis by dexamethasone might be a hint of further anti-inflammatory
      mechanisms of glucocorticoids.

PMID- 19596030
TI  - Influence of long-term growth hormone replacement on leptin and ghrelin in GH
      deficiency before and after glucose load.
AB  - INTRODUCTION: This cross-sectional study was performed to evaluate the effect of
      long-term GH substitution on leptin and ghrelin in GH deficiency (GHD). METHODS:
      Leptin and ghrelin were measured after glucose load for 3 h in 52 pat and 10 age-
      and BMI-matched healthy controls. 22 GHD pat were on GH substitution (GH-Sub) for
      a median of 10 yr (range 2-27 yr). 30 age- and BMI-matched GHD pat were not
      substituted for at least 2 yr (non-Sub). RESULTS: Basal leptin (8 microg/l (1
      130) vs. 16 microg/l (3-89), p<0.05) and AUC of leptin (p<0.05) was significantly
      lower in GH-Sub compared to non-Sub. In the control group, leptin was higher
      compared to GH-Sub and similar to non-Sub (19 microg/l (4-57)). Ghrelin
      (baseline: non-Sub 113 ng/l (61-270), GH-Sub 145 ng/l (83-280), controls 131 ng/l
      (83-274)) were slightly but not significantly lower for non-Sub. After glucose
      load, a significant decrease in leptin appeared in both GHD groups, but not in
      the control group. Ghrelin decreased significantly in all groups. CONCLUSION:
      Lipolytic GH causes lower leptin in GH-Sub. The reason for similar ghrelin might
      be the compensating effect of acute GH suppression and stimulating low fat mass
      on ghrelin. Leptin regulation after glucose load is impaired in GHD, whereas
      ghrelin regulation seems to be not effected.

PMID- 19596028
TI  - Investigating the depth electrode-brain interface in deep brain stimulation using
      finite element models with graded complexity in structure and solution.
AB  - Deep brain stimulation (DBS) is an increasingly used surgical therapy for a range
      of neurological disorders involving the long-term electrical stimulation of
      various regions of the human brain in a disorder specific manner. Despite being
      used for the last 20 years, the underlying mechanisms are still not known, and
      disputed. In particular, when the electrodes are implanted into the human brain,
      an interface is created with changing biophysical properties which may impact on
      stimulation. We previously defined the electrode-brain interface (EBI) as
      consisting of three structural elements: the quadripolar DBS electrode, the peri
      electrode space and the surrounding brain tissue. In order to understand more
      about the nature of this EBI, we used structural computational models of this
      interface, and estimated the effects of stimulation using coupled axon models.
      These finite element models differ in complexity, each highlighting a different
      feature of the EBI's effect on the DBS-induced electric field. We show that the
      quasi-static models are sufficient to demonstrate the difference between the
      acute and chronic clinical stages post-implantation. However, the frequency
      dependent models are necessary as the waveform shaping has a major influence on
      the activation of neuronal fibres. We also investigate anatomical effects on the
      electric field, by taking specific account of the ventricular system in the human
      brain. Taken together, these models allow us to visualise the static, dynamic and
      target specific properties of the DBS-induced field in the surrounding brain
      regions.

PMID- 19596031
TI  - Prion protein detection via direct immuno-quantitative real-time PCR.
AB  - We describe a simple and robust assay for the quantitative detection of prions
      using immuno-quantitative real-time PCR (iQ-RT-PCR) made possible by a direct
      conjugate of a prion-specific antibody (ICSM35) and a synthetic 99-bp DNA tail.
      The DNA tail was engineered to include a single ScrFI restriction site, which
      enabled subsequent quantification of restricted DNA tails using real-time PCR.
      The assay was tested with scrapie prions bound to polyvinylidene difluoride
      membranes and to 96-well plates coated with a capturing antibody from a
      commercially available immuno-based assay (TeSeE). The iQ-RT-PCR assay had a
      detection limit corresponding to 2.32x10(2) prion epitopes, which represented a
      1000-fold increase in detection sensitivity over the commercial assay. Detection
      of prions from diluted scrapie-positive brain homogenate bound to membranes was
      linear over a range of 1.06x10(4) to 3.24x10(2) epitopes (R(2)=0.92). Given its
      sensitivity and versatility, the present assay has potential to enable rapid and
      reliable detection of agents causing transmissible spongiform encephalopathies.

PMID- 19596033
TI  - Enhanced mucosal vaccination by biodegradable nanoparticles.

PMID- 19596034
TI  - The design of polyvalent scaffolds for targeted delivery.
AB  - Nature makes extensive use of polyvalency-the simultaneous binding of multiple
      ligands to multiple complementary receptors. The concept of polyvalency can also
      be used to design synthetic scaffolds for applications ranging from the design of
      inhibitors for toxins and pathogens to delivery and imaging. This article reviews
      recent developments in the design of polyvalent constructs suitable for targeted
      delivery. Specifically, we will discuss recent developments in the design of
      scaffolds, the identification of ligands for targeting, and the presentation of
      ligands on the scaffold to optimize affinity and specificity for the target.

PMID- 19596032
TI  - The extent of genetic diversity of Epstein-Barr virus and its geographic and
      disease patterns: a need for reappraisal.
AB  - Epstein-Barr virus (EBV) is a ubiquitous, gamma-1 lymphotrophic virus
      etiologically linked to nasopharyngeal carcinoma (NPC), endemic to Southern
      China, and Burkitt lymphoma (BL), endemic to equatorial Africa, both of which are
      rare elsewhere in the world. Why EBV is associated with different malignancies in
      different geographic regions remains puzzling and may be related to EBV genotypic
      variability through specific disease and geographic associations. We review the
      literature on sequence variation in EBV genes, focusing on LMP-1, EBNA-1, and
      BZLF-1 and their distribution by geography and disease. Given the limitations of
      current studies, definitive conclusions regarding the link between EBV genotypes,
      disease and geography are not possible. We suggest that the true extent of EBV
      diversity is likely to be greater than is currently recognized. Additional
      studies conducted in carefully selected populations, that are sufficiently
      powered to provide robust estimates, and that utilize testing approaches that
      permit full characterization of viral diversity are needed to further our
      understanding of patterns of EBV genetic variation and their association with
      malignancies in different regions.

PMID- 19596035
TI  - Aging is associated with a numerical and functional decline in plasmacytoid
      dendritic cells, whereas myeloid dendritic cells are relatively unaltered in
      human peripheral blood.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that initiate and
      regulate T-cell responses. In this study, the numbers and functional cytokine
      secretions of plasmacytoid and myeloid DC (pDC and mDC, respectively) in
      peripheral blood from young and elderly subjects were compared. Overall, pDC
      numbers in peripheral blood were lower in healthy elderly compared with healthy
      young subjects (p = 0.016). In response to influenza virus stimulation, isolated
      pDC from healthy elderly subjects secreted less interferon (IFN)-alpha compared
      with those from healthy young subjects. The decline in IFN-alpha secretion was
      associated with a reduced proportion of pDC that expressed Toll-like receptor-7
      or Toll-like receptor-9. In contrast, there was little difference in the numbers
      and cytokine secretion function between healthy young and healthy elderly
      subjects (p = 0.82). However, in peripheral blood from frail elderly subjects,
      the numbers of mDC were severely depleted as compared with either healthy young
      or elderly subjects (p = 0.014 and 0.007, respectively). Thus, aging was
      associated with the numerical and functional decline in pDC, but not mDC, in
      healthy young versus elderly subject group comparisons, while declining health in
      the elderly can profoundly impact mDC negatively. Because of the importance of
      pDC for antiviral responses, the age-related changes in pDC likely contribute to
      the impaired immune response to viral infections in elderly persons, especially
      when combined with the mDC dysfunction occurring in those with compromised
      health.

PMID- 19596036
TI  - Peony glycosides produce antidepressant-like action in mice exposed to chronic
      unpredictable mild stress: effects on hypothalamic-pituitary-adrenal function and
      brain-derived neurotrophic factor.
AB  - The root part of Paeonia lactiflora Pall. (Ranunculaceae), commonly known as
      peony, is a commonly used Chinese herb for the treatment of depression-like
      disorders. Previous studies in our laboratory have demonstrated that total
      glycosides of peony (TGP) produced antidepressant-like action in various mouse
      models of behavioral despair. The present study aimed to examine whether TGP
      could affect the chronic unpredictable mild stress (CUMS)-induced depression in
      mice. The mechanism(s) underlying the antidepressant-like action was investigated
      by measuring serum corticosterone level, glucocorticoid receptor (GR) and brain
      derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being
      lasted for 6 weeks, caused depression-like behavior in mice, as indicated by the
      significant decrease in sucrose consumption and increase in immobility time in
      the forced swim test. Whereas serum corticosterone level was significantly
      increased in mice exposed to CUMS, expressions of GR mRNA in hippocampus, and
      BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated mice.
      Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the six
      weeks of CUMS significantly suppressed behavioral and biochemical changes induced
      by CUMS. The results suggest that the antidepressant-like action of TPG is likely
      mediated by modulating the function of hypothalamic-pituitary-adrenal axis and
      increasing the expression of BDNF in brain tissues.

PMID- 19596037
TI  - Gray matter reduction associated with emotion regulation in female outpatients
      with major depressive disorder: a voxel-based morphometry study.
AB  - OBJECTIVE: Though emotion dysregulation is the key feature in major depressive
      disorder, and structural changes in brain areas of depressed patients have been
      found, it is unknown how these regional volume alterations correlate with the
      ability to regulate emotion in the depressed population. METHOD: We examined the
      gray matter concentration (GMC) and volume (GMV) in 17 depressed patients and 17
      healthy volunteers using a voxel-based morphometry (VBM) study. Images were
      acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented.
      Statistical comparisons were performed using the general linear model. The
      identified volumetric alterations in the depressed participants were correlated
      with their performance on an emotion regulation task that involved reduction of
      positive or negative emotions to emotional pictures that were selected according
      to their individual ratings. RESULTS: The depressed participants showed specific
      difficulty in regulating negative emotion, though not positive emotion, which was
      associated with reduced GMV and concentration in the anterior cingulate cortex
      (ACC) and the inferior orbitofrontal cortex (OFC). Decreased GMC in the superior
      temporal cortex was also found in people with major depressive disorder.
      CONCLUSIONS: Abnormal structures in the ACC and OFC and the dysregulation of
      negative emotion may relate to the pathology of major depressive disorder.

PMID- 19596038
TI  - Antidepressant properties of the 5-HT4 receptor partial agonist, SL65.0155:
      behavioral and neurochemical studies in rats.
AB  - This study was undertaken to investigate the potential antidepressant-like
      properties of SL65.0155, a serotonin 5-HT(4) receptor partial agonist, in male
      rats of the Wistar strain tested in the forced swim test (FST), an experimental
      model widely used to assess antidepressant-like activity. The expression of
      hippocampal neurotrophic factors, such as the brain-derived neurotrophic factor
      (BDNF), the phosphorilated cAMP response element-binding protein (p-CREB), the B
      cell lymphoma-2 (Bcl-2), the Bax and the vascular endothelium growth factor
      (VEGF) were also evaluated by Western Blot analysis. Different groups of rats
      received intraperitoneally (i.p.) injections of SL65.0155 (0.1, 0.5 and 1 mg/kg),
      clomipramine (50 mg/kg), citalopram (15 mg/kg) or vehicle, respectively, 24, 5
      and 1 h prior to the FST. Compared to the control group, SL65.0155 (0.5 and 1
      mg/kg), clomipramine or citalopram injected animals showed an increased swimming
      and climbing behavior and reduced immobility time in the FST. Interestingly, this
      effect was not due to changes in the locomotor activity since all treated groups
      failed to show any change in motor ability as assessed in the open field test.
      Western blot analysis of hippocampal homogenates showed an enhancement of p-CREB,
      BDNF Bcl-2 and VEGF protein levels in SL65.0155 treated groups, but not in
      citalopram or clomipramine treated groups, used here as positive control. No
      change was found in Bax expression in any treated group. These findings give
      further support to the hypothesis that the stimulation of serotonin 5-HT(4)
      receptors may be a therapeutic target for depression.

PMID- 19596039
TI  - Platelet poor plasma serotonin level in delinquent adolescents diagnosed with
      conduct disorder.
AB  - OBJECTIVE: Accumulating data indicate the involvement of the serotonergic system
      in adolescent aggression. The aim of this study was to examine the platelet-poor
      plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with
      conduct disorder (CD) in comparison with normal controls. METHOD: PPP 5-HT levels
      were measured in 16 male delinquent CD adolescents from a correctional facility
      and in 14 normal male adolescent controls. Severity of aggressive behavior was
      assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale
      (OAS). RESULTS: Delinquent CD adolescents had higher PPP 5-HT levels (about 3
      fold) than the normal controls (27.68+/-32.29 vs. 7.76+/-4.23 ng/ml,
      respectively, p=0.027). In the delinquent CD adolescents a significant
      correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive
      scores (r=0.68, p=0.0034 and r=0.59, p=0.016, respectively). CONCLUSIONS:
      Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT
      neurotransmission may have a role in the symptomatology and treatment of severe
      adolescent CD.

PMID- 19596040
TI  - Selenium tissue distribution changes after ethanol exposure during gestation and
      lactation: selenite as a therapy.
AB  - Ethanol consumption affects maternal nutrition and antioxidant status together
      with the future health of their progeny. Selenium (Se) is a trace element with
      antioxidant activity; we will study the effect of ethanol in dams on Se
      bioavailability, antioxidant balance and gestational parameters. We also will
      study if a Se-supplemented diet (0.5 ppm) administered to ethanol-exposed dams
      avoids the undesirable effects provoked by ethanol. We have used four
      experimental groups: control (C); chronic ethanol (A); control+Se (CS) and
      chronic ethanol+Se (AS). Se levels in serum, urine, faeces, and several tissues
      were measured by graphite-furnace atomic absorption spectrometry. Serum
      glutathione peroxidase (GPx) activity was determined by spectrometry. Se
      bioavailability is altered by ethanol, causing a decrease in Se retention,
      reducing Se levels in cortex, muscle, mammary gland and salivary gland while
      elevating Se values in heart, liver and spleen. On the other hand, Se
      supplementation increases some of these parameters. Serum GPx activity was
      decreased by ethanol, while a Se-supplemented diet restores these values to those
      found in controls. We have demonstrated that ethanol decreased Se retention in
      dams, affecting their tissues' Se deposits, decreasing GPx activity in serum,
      gestational parameters and the weight of their progeny. Selenite supplementation
      counteracts these decreasing effects, except in cortex.

PMID- 19596041
TI  - c-Myc mediates a hypoxia-induced decrease in acetylated histone H4.
AB  - Global acetylation of histone H4 is a mark of gene transcriptional activation.
      The c-Myc transcription factor binds to specific DNA sites in cellular chromatin
      and induces the acetylation of histone H4. In this study, hypoxia (1% Oxygen)
      induced a decrease in both global acetylated histone H4 (AcH4) and c-Myc in human
      lung carcinoma A549 cells and in human bronchial epithelial Beas-2B cells, The
      decline was more striking in A549 cells compared to Beas2-B cells, when cells
      were exposed to hypoxic stress for 24 h. Further studies showed that these
      alterations of global AcH4 can be attributed to the decrease in c-Myc protein
      levels. While hypoxia-induced gene activation is known to be mediated by Hypoxia
      Response Elements (HRE), the mechanism for down-regulation of genes by hypoxia is
      not known. The decrease in c-Myc protein levels induced by hypoxia may contribute
      to hypoxia-induced gene repression.

PMID- 19596042
TI  - Molecular identification of omega-amidase, the enzyme that is functionally
      coupled with glutamine transaminases, as the putative tumor suppressor Nit2.
AB  - Our purpose was to identify the sequence of omega-amidase, which hydrolyses the
      amide group of alpha-ketoglutaramate, a product formed by glutamine
      transaminases. In the Bacillus subtilis genome, the gene encoding a glutamine
      transaminase (mtnV) is flanked by a gene encoding a putative 'carbon-nitrogen
      hydrolase'. The closest mammalian homolog of this putative bacterial omega
      amidase is 'nitrilase 2', whose size and amino acid composition were in good
      agreement with those reported for purified rat liver omega-amidase. Mouse
      nitrilase 2 was expressed in Escherichia coli, purified and shown to catalyse the
      hydrolysis of alpha-ketoglutaramate and other known substrates of omega-amidase.
      No such activity was observed with mouse nitrilase 1. We conclude that mammalian
      nitrilase 2 is omega-amidase.

PMID- 19596043
TI  - Auditory size-deviant detection in adults and newborn infants.
AB  - Auditory size perception refers to the ability to make accurate judgements of the
      size of a sound source based solely upon the sound emitted from the source.
      Electro-physiological and behavioural data were collected to test whether sound
      source size parameters are detected from task-irrelevant sequences in adults and
      newborn infants. The mismatch negativity (MMN) obtained from adults indexed
      automatic detection of changes in size for voices, musical instruments and animal
      calls, regardless of whether the acoustic change indicated larger or smaller
      sources. Neonates detected changes in the size of a musical instrument. The data
      are consistent with the notion that auditory size-deviant detection in humans is
      an innate automatic process. This conclusion is compatible with the theory that
      the ability to assess the size of sound sources evolved because it provided
      selective advantage of being able to detect larger (more competent) suitors and
      larger (more dangerous) predators.

PMID- 19596045
TI  - Day-to-day variation in saliva cortisol--relation with sleep, stress and self
      rated health.
AB  - The objective was to examine the day-to-day variation in cortisol among healthy
      individuals and its relation to the time of saliva sampling, work, stress and
      fatigue. During 4 consecutive weeks, 14 office workers provided saliva samples
      (at awakening, 15 min after awakening and at bedtime) and made diary ratings for
      each day. Results showed a variation in cortisol values between participants but
      also within individuals. After controlling for the individual differences,
      results showed that low cortisol levels in the morning were associated with
      sleepiness at awakening and anxiety, exhaustion, and poor health the day before.
      High evening levels of cortisol were associated with symptoms of stress and poor
      self-rated health. Further analysis of the cortisol awakening response (CAR)
      showed that all participants had a mixture of both a positive and negative
      responses. During mornings with a negative response participants stayed in bed
      for a longer time after the initial awakening, which might be a sign of snoozing,
      thus missing the awakening response.

PMID- 19596044
TI  - Respiratory sinus arrhythmia reactivity predicts emotion regulation and
      depressive symptoms in at-risk and control children.
AB  - We examined respiratory sinus arrhythmia (RSA), emotion regulation (ER), and
      prospective depressive symptoms in children at risk for depression and controls.
      Of the 65 children (35 boys; 5-13 years) in the sample, 39 had a parent with
      childhood-onset mood disorder and 26 had a parent with no history of major
      psychiatric disorder. RSA during pre- and post-film baselines and RSA reactivity
      to sad film clip were measured. Later, children's ER responses (focusing on
      sad/distressing affect) were assessed using a parent-reported questionnaire, and
      depressive symptoms were measured via clinical ratings. Results indicated that,
      compared to the initial baseline, a greater decrease in RSA (i.e., more vagal
      withdrawal) in response to the sad film clip predicted more adaptive ER responses
      and lower levels of clinician-rated depressive symptoms. However, tests for ER as
      a mediator of the association between RSA reactivity and depressive symptoms were
      precluded because maladaptive, but not adaptive, ER was associated with
      depressive symptoms. Overall, results suggest that cardiac vagal withdrawal (a
      greater decrease in RSA) in response to an emotional stimulus reflects more
      adaptive parasympathetic activity, which could facilitate children's ability to
      effectively manage their sadness and distress and predict lower risk of
      depressive symptoms over time.

PMID- 19596046
TI  - Heart rate and skin conductance in four-year-old children with aggressive
      behavior.
AB  - Autonomic underarousal, indicated by low heart rate (HR) and skin conductance
      level (SCL), is related to childhood aggression. However, results are
      inconsistent in preschoolers. We assessed HR, SCL, heart rate reactivity and skin
      conductance reactivity in four-year-old children. Comparisons were made between
      children with a high level and with a low level of aggressive behavior according
      to the Child Behavior Checklist 1 1/2-5 as well as between children who were
      diagnosed with Oppositional Defiant Disorder or Conduct Disorder (ODD/CD) and
      children with a low level of aggression. Preschool children with a high level of
      aggressive behavior showed lower SCL and SCR and children with ODD/CD showed
      lower SCL. In contrast, we did not find lower HR and HRR in preschool children
      with a high level of aggressive behavior or ODD/CD. Thus, results suggest that
      decreased SCL, but not HR, is a characteristic of preschool children with
      aggressive behavior or ODD/CD.

PMID- 19596047
TI  - Cellular "bauplans": evolving unicellular forms by means of Julia sets and
      Pickover biomorphs.
AB  - The universe of cellular forms has received scarce attention by mainstream neo
      Darwinian views. The possibility that a fundamental trait of biological order may
      consist upon, or be guided by, developmental processes not completely amenable to
      natural selection was more akin to previous epochs of biological thought, i.e.
      the "bauplan" discussion. Thirty years ago, however, Lynn and Tucker studied the
      biological mechanisms responsible for defining organelles position inside cells.
      The fact that differentiated structures performing a specific function within the
      eukaryotic cell (i.e. mitochondrion, vacuole, or chloroplast) were occupying
      specific positions in the protoplasm was the observational and experimental
      support of the 'morphogenetic field' notion at the cellular level. In the present
      paper we study the morphogenetic field evolution yielding from an initial
      population of undifferentiated cells to diversified unicellular organisms as well
      as specialized eukaryotic cell types. The cells are represented as Julia sets and
      Pickover biomorphs, simulating the effect of Darwinian natural selection with a
      simple genetic algorithm. The morphogenetic field "defines" the locations where
      cells are differentiated or sub-cellular components (or organelles) become
      organized. It may be realized by different possibilities, one of them by
      diffusing chemicals along the Turing model. We found that Pickover cells show a
      higher diversity of size and form than those populations evolved as Julia sets.
      Another novelty is the way that cellular organelles and cell nucleus fill in the
      cell, always in dependence on the previous cell definition as Julia set or
      Pickover biomorph. Our findings support the existence of specific attractors
      representing the functional and stable form of a differentiated cell-genuine
      cellular bauplans. The configuration of the morphogenetic field is "attracted"
      towards one or another attractor depending on the environmental influences as
      modeled by a particular fitness function. The model promotes the classical
      discussions of D'Arcy Thompson and the more recent views of Waddington, Goodwin
      and others that consider organisms as dynamical systems that evolve through a
      'master plan' of transformations, amenable to natural selection. Intriguingly,
      the model also connects with current developments on mechanobiology, highlighting
      the informational-developmental role that cytoskeletons may play.

PMID- 19596048
TI  - Ischemic tolerance in the cochlea.
AB  - Ischemic tolerance in the cochlea was investigated in a gerbil model of cochlear
      ischemia. Transient cochlear ischemia was produced by extracranial occlusion of
      the bilateral vertebral arteries. The gerbils were divided into two groups;
      single ischemia group and double ischemia group. In the single ischemia group,
      animals were subjected to lethal cochlear ischemia for 15 min. In the double
      ischemia group, animals were subjected to sublethal cochlear ischemia for 2 min
      at 2 days before lethal ischemia for 15 min. Consequently, sublethal ischemia
      prevented lethal ischemia-induced hair cell degeneration and ameliorated hearing
      impairment, suggesting ischemic tolerance in the cochlea.

PMID- 19596050
TI  - Non-competitive metabotropic glutamate 1 receptor antagonists block activity of
      slowly adapting type I mechanoreceptor units in the rat sinus hair follicle.
AB  - Previous studies suggested that Group I metabotropic glutamate (mGlu) receptors
      play a role in mechanotransduction processes of slowly adapting type I
      mechanoreceptors. Using an isolated rat sinus hair follicle preparation we tested
      a range of compounds. Surprisingly, only non-competitive mGlu1 receptor
      antagonists produced profound and long-lasting depression of mechanically evoked
      firing. 6-Amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-alpha]benzimidazole-2
      carboxamide hydrochloride (YM-298198) had an IC(50) of 8.7 muM (95% CI 5.7 to
      13.2 microM), representing the most potent known blocker of type I
      mechanoreceptors. The derivative 6-amino-N-cyclohexyl-3-methylthiazolo[3,2
      alpha]benzimidazole-2-carboxamide hydrochloride (desmethyl YM-298198) had a
      comparable potency. Another compound 7-(hydroxyimino)cyclopropa[b]chromen-1a
      carboxylate ethyl ester (CPCCOEt) had a similar depressant effect, although it
      was less potent with an approximate IC(50) of 100 microM. Between three and seven
      times the concentration of CPCCOEt and YM-298198 respectively was required to
      produce similar depressions in slowly adapting type II units. No depression, and
      some weak excitatory effects, were observed using the following ligands: the
      competitive mGlu1 receptor antagonist alpha-amino-5-carboxy-3-methyl-2
      thiopheneacetic acid (3-MATIDA) (300 microM), the phosphoserine phosphatase
      inhibitor dl-2-amino-3-phosphonopropionic acid (dl-AP3) (2 mM), non-competitive
      mGlu5 receptor antagonists 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; (S)
      3,5-DHPG, (S)-3,5-dihydroxyphenylglycine (MTEP) (10 microM) and 2-methyl-6
      (phenylethynyl)pyridine hydrochloride (MPEP) (100 microM), the mGlu1 receptor
      agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) (500 microM), and the mGlu5
      receptor agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) (1 mM). The results
      suggest that the non-competitive mGlu1 receptor antagonists are not acting at
      conventional mGlu1 receptors but at other binding sites, possibly those directly
      associated with mechanogated channels or on any of a number of indirect
      biochemical pathways. YM-298198 and related compounds may prove to be useful
      ligands to identify mechanosensitive channel proteins. The selective interference
      of type I units may provide further evidence that Merkel cells are
      mechanotransducers. Finally such compounds may deliver insights or treatments for
      Merkel cell carcinoma.

PMID- 19596049
TI  - The voltage-gated Na+ channel beta3 subunit does not mediate trans homophilic
      cell adhesion or associate with the cell adhesion molecule contactin.
AB  - Voltage-gated Na(+) channel (VGSC) beta1 and beta2 subunits are multifunctional,
      serving as both channel modulators and cell adhesion molecules (CAMs). The
      purpose of this study was to determine whether VGSC beta3 subunits function as
      CAMs. The beta3 extracellular domain is highly homologous to beta1, suggesting
      that beta3 may also be a functional CAM. We investigated the trans homophilic
      cell adhesive properties of beta3, its association with the beta1-interacting CAM
      contactin, as well as its ability to interact with the cytoskeletal protein
      ankyrin. Our results demonstrate that, unlike beta1, beta3 does not participate
      in trans homophilic cell-cell adhesion or associate with contactin. Further,
      beta3 does not associate with ankyrin(G) in a heterologous system. Previous
      studies have shown that beta3 interacts with the CAM neurofascin-186 but not with
      VGSC beta1. Taken together, these findings suggest that, although beta1 and beta3
      exhibit similar channel modulatory properties in heterologous systems, these
      subunits differ with regard to their homophilic and heterophilic CAM binding
      profiles.

PMID- 19596051
TI  - Role of alpha2/delta subunit in the development of morphine-induced rewarding
      effect and behavioral sensitization.
AB  - Previous data demonstrate that L-type voltage-gated calcium channel (VGCC)
      blockers, which bind to alpha(1) subunits of VGCC to suppress Ca(2+) entry into
      cells, inhibit the development of psychological dependence on drugs of abuse,
      suggesting the upregulation of L-type VGCC in the development of psychological
      dependence. However, there are few available data on changes of the auxiliary
      subunit alpha(2)/delta modifying L-type VGCC under such conditions. We therefore
      investigated here the role of alpha(2)/delta subunits of VGCCs in the brain of
      mouse after repeated treatment with morphine. The treatment with morphine
      increased alpha(2)/delta subunit expression in the frontal cortex and the limbic
      forebrain of mice showing rewarding effect and sensitization to hyperlocomotion
      by morphine. The morphine-induced behavioral sensitization and place preference
      were also suppressed by gabapentin, which binds to an exofacial epitope of the
      alpha(2)/delta auxiliary subunits of VGCCs. These findings indicate that the
      upregulation of alpha(2)/delta subunit as well as alpha(1) subunits of VGCC in
      the frontal cortex and the limbic forebrain plays a critical role in development
      of morphine-induced rewarding effect and behavioral sensitization following
      neuronal plasticity.

PMID- 19596052
TI  - Long-term green tea catechin administration prevents spatial learning and memory
      impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42
      oligomers and upregulating synaptic plasticity-related proteins in the
      hippocampus.
AB  - The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset
      of learning and memory deficits along with spontaneous overproduction of soluble
      beta-amyloid peptide (Abeta) in the brain. In our study, 4 month old male SAMP8
      mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in
      drinking water for 6 months. We found that a supplementation with 0.05% or 0.1%
      GTC prevented spatial learning and memory impairments of mice in the Morris water
      maze. Better performance of GTC-treated mice was associated with decreased levels
      of Abeta(1-42) oligomers in the hippocampus. The activity of the protein kinase
      A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular
      targets of Abeta oligomers which is crucial for late long-term potentiation and
      long-term memory formation, was significantly increased after GTC administration.
      We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions
      of three representative proteins of synaptic function and synaptic structure,
      including brain-derived neurotrophic factor(BDNF), post-synaptic density protein
      95 (PSD95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). These
      results demonstrated that long-term 0.05% or 0.1% green tea catechin
      administration may prevent spatial learning and memory decline of SAMP8 mice by
      decreasing Abeta(1-42) oligomers and upregulating synaptic plasticity-related
      proteins in the hippocampus.

PMID- 19596053
TI  - Chronic omega-3 supplementation in seizure-prone versus seizure-resistant rat
      strains: a cautionary tale.
AB  - Several studies have shown fatty acid supplementation to be efficacious in the
      treatment of attention deficit hyperactivity disorder/autism spectrum disorder
      (ADHD/ASD) and epilepsy. Interestingly, rats bred to be seizure-prone (Fast),
      unlike those bred for seizure-resistance (Slow), naturally exhibit behaviors and
      physiology reminiscent of ADHD/ASD in humans, suggesting a fundamental link
      between seizure disposition and these developmental disorders. To determine
      whether chronic omega-3 supplementation might ameliorate ADHD-like behaviors in
      the seizure-prone rat strain and/or alter natural predispositions for or against
      seizure in either strain, Fast and Slow weanlings were maintained on a control or
      omega-3-supplemented diet. As adults, rats were tested in paradigms known to
      elicit ADHD-like behaviors from Fast rats and then kindled from the amygdala to
      assess relative seizure disposition. While omega-3 supplementation did not
      significantly alter the relative hyperactivity, learning deficits or heightened
      seizure sensitivity naturally exhibited by Fast rats, it dramatically reduced
      their impulsivity to Slow-like levels. In contrast, typical behavioral patterns
      in Slow rats were largely unaffected by omega-3 supplementation yet their
      proclivity for seizure was greatly increased. This heightened vulnerability to
      seizure in Slow rats was paralleled by a drop in circulating plasma non
      esterified fatty acids (NEFA) to match levels normally observed in Fast rats.
      These findings suggest a delicate balance between seizure predisposition and ADHD
      like behaviors that can be influenced by omega-3 treatment. Further, a
      relationship between circulating NEFA levels and seizure susceptibility has
      surfaced that advocates caution when treating different genetic backgrounds with
      omega-3 fatty acids.

PMID- 19596054
TI  - Identification of the neural pathway underlying spontaneous crossed phrenic
      activity in neonatal rats.
AB  - Cervical spinal cord hemisection at C2 leads to paralysis of the ipsilateral
      hemidiaphragm in rats. Respiratory function of the paralyzed hemidiaphragm can be
      restored by activating a latent respiratory motor pathway in adult rats. This
      pathway is called the crossed phrenic pathway and the restored activity in the
      paralyzed hemidiaphragm is referred to as crossed phrenic activity. The latent
      neural pathway is not latent in neonatal rats as shown by the spontaneous
      expression of crossed phrenic activity. However, the anatomy of the pathway in
      neonatal rats is still unknown. In the present study, we hypothesized that the
      crossed phrenic pathway may be different anatomically in neonatal and adult rats.
      To delineate this neural pathway in neonates, we injected wheat germ agglutinin
      conjugated to horseradish peroxidase (WGA-HRP), a retrograde transsynaptic
      tracer, into the phrenic nerve ipsilateral to hemisection. We also injected
      cholera toxin subunit B-horseradish peroxidase (BHRP) into the ipsilateral
      hemidiaphragm following hemisection in other animals to determine if there are
      midline-crossing phrenic dendrites involved in the crossed phrenic pathway in
      neonatal rats. The WGA-HRP labeling was observed only in the ipsilateral phrenic
      nucleus and ipsilateral rostral ventral respiratory group (rVRG) in the postnatal
      day (P) 2, P7, and P28 hemisected rats. Bilateral labeling of rVRG neurons was
      shown in P35 rats. The BHRP study showed that many phrenic dendrites cross the
      midline in P2 neonatal rats at both rostral and caudal parts of the phrenic
      nucleus. There was a marked reduction of crossing dendrites observed in P7 and
      P28 animals and no crossing dendrites observed in P35 rats. The present results
      suggest that the crossed phrenic pathway in neonatal rats involves the parent
      axons from ipsilateral rVRG premotor neurons that cross at the level of obex as
      well as decussating axon collaterals that cross over the spinal cord midline to
      innervate ipsilateral phrenic motoneurons following C2 hemisection. In addition,
      midline-crossing dendrites of the ipsilateral phrenic motoneurons may also
      contribute to the crossed phrenic pathway in neonates.

PMID- 19596055
TI  - Sensory activity differentially modulates N-methyl-D-aspartate receptor subunits
      2A and 2B in cortical layers.
AB  - Activity-dependent modulation of N-methyl-d-aspartate (NMDA) receptors containing
      selective NR2 subunits has been implicated in plastic processes in developing and
      adult sensory cortex. Aiming to reveal differential sensitivity of NR2 subunits
      to sustained changes in sensory activity, we utilized four paradigms that
      blocked, reinstated, or initiated sensory visual activity. Laminar prevalence of
      N-methyl-d-aspartate receptor subunit 2A- (NR2A)- and N-methyl-d-aspartate
      receptor subunit 2B- (NR2B)-containing synapses in visual cortex of postnatal and
      adult ferrets was assessed using quantitative electron microscopy. Light
      deprivation at all ages resulted in a downregulation of NR2A, while recovery from
      deprivation resulted in an upregulation. Furthermore, premature eyelid opening
      caused a precocious increase of NR2A. Thus, transitions between periods of dark
      and light rapidly and bidirectionally regulate NR2A, regardless of cortical layer
      or age. In contrast, NR2B regulation is layer- and age-dependent. Only in layer
      IV, NR2B prevalence displays a one-time decline about 3 weeks after the
      initiation of sensory activity upon normal or premature eyelid opening, or upon
      termination of dark-rearing. Incongruity in patterns of NR2A and NR2B modulation
      by activity is consistent with involvement of these subunits in two distinct, yet
      partially co-occurring processes: developmental plasticity with a critical
      period, and lifelong plasticity that is established in early developmental ages.

PMID- 19596057
TI  - Novel approach to bioequivalence assessment based on physiologically motivated
      model.
AB  - The study was conducted to exemplify an approach capable of obtaining a new
      insight into bioequivalence (BE) assessment, by the use of a physiologically
      motivated model. Data from an oral BE study of two piroxicam (PXM) products was
      used as an example. The BE study was carried out with 24 healthy European
      subjects according to a two-sequence crossover-randomized design. The test and
      reference formulations were a PXM generic formulation (LaborMed Pharma, Romania)
      and Feldene (Pfizer, USA), respectively. Plasma concentrations of PXM were
      monitored by a validated high-performance liquid chromatography over a period of
      144 h after administration. After the structure of the optimal model was
      selected, parameters that characterized the whole-body disposition behavior of
      PXM in the subjects were derived. The paired Student's t-test and Wilkoxon's test
      were performed on the derived parameters. The null hypothesis of no differences
      in the parameters of the whole-body disposition behavior of PXM related to the
      test and reference product was not rejected at 5% level of significance. This
      result suggested that the compared products were bioequivalent and could be used
      interchangeably in clinical setting. The presented approach might show a new way,
      worth incorporating in future BE guidelines.

PMID- 19596058
TI  - Monitoring crystallisation of drugs from fast-dissolving oral films with
      isothermal calorimetry.
AB  - The aim of this study was to evaluate the potential of isothermal calorimetry to
      monitor and characterize crystallisation in drug-loaded fast-dissolving oral
      films. Films of polyvinylpyrrolidone (PVP) containing indomethacin were cast into
      glass ampoules; stability was assessed by monitoring the power changes occurring
      with time. Three grades of PVP (K10, K25 and K40, where the number multiplied by
      1000 gives the average molecular weight) were used. Indomethacin was seen to
      crystallise from all PVP grades over ca. 24-48 h at two study temperatures (25
      and 37 degrees C), as denoted by a large exothermic event. At 25 degrees C the
      exothermic event was a single peak; at 37 degrees C two peaks were observed.
      Subsequent analysis of the crystals with differential scanning calorimetry (DSC)
      and polarized light microscopy determined that the stable gamma-polymorph of
      indomethacin formed at 25 degrees C while both the gamma- and metastable alpha
      polymorphs formed at 37 degrees C. The calorimetric data were converted to
      relative crystallinity as a function of time and analysed with three
      crystallisation models (Avrami, Tobin and Urbanovici-Segal) to determine
      crystallisation kinetics. Of the three models applied the Urbanovici-Segal model
      best described the data, although this may be because this model contains a term
      that effectively accounts for deviation from the Avrami model. The rate constants
      determined were broadly consistent irrespective of the model used. Increasing
      polymer molecular weight did not generally affect the crystallisation rate,
      although an increase in temperature did result in a concomitant increase in
      crystallisation rate. The data suggest that isothermal calorimetry is able to
      monitor drug crystallisation in polymer films and therefore the technique could
      be a useful tool for conducting stability assays for fast-dissolving oral
      medicines.

PMID- 19596056
TI  - Striatal neuroprotection with methylene blue.
AB  - Recent literature indicates that low-dose Methylene Blue (MB), an autoxidizable
      dye with powerful antioxidant and metabolic enhancing properties, might prevent
      neurotoxin-induced neural damage and associated functional deficits. This study
      evaluated whether local MB may counteract the anatomical and functional effects
      of the intrastriatal infusion of the neurotoxin rotenone (Rot) in the rat. To
      this end, stereological analyses of striatal lesion volumes were performed and
      changes in oxidative energy metabolism in the striatum and related motor regions
      were mapped using cytochrome oxidase histochemistry. The influence of MB on
      striatal levels of oxidative stress induced by Rot was determined, and behavioral
      tests were used to investigate the effect of unilateral MB coadministration on
      motor asymmetry. Rot induced large anatomical lesions resembling "metabolic
      strokes," whose size was greatly reduced in MB-treated rats. Moreover, MB
      prevented the decrease in cytochrome oxidase activity and the perilesional
      increase in oxidative stress associated with Rot infusion in the striatum. MB
      also prevented the indirect effects of the Rot-induced lesion on cytochrome
      oxidase activity in related motor regions, such as the striatal regions rostral
      and caudal to the lesion, the substantia nigra compacta and reticulata, and the
      pedunculopontine nucleus. At a network level, MB maintained a global
      strengthening of functional connectivity in basal ganglia-thalamocortical motor
      circuits, as opposed to the functional decoupling observed in Rot-alone subjects.
      Finally, MB partially prevented the behavioral sensorimotor asymmetries elicited
      by Rot. These results are consistent with protective effects of MB against
      neurotoxic damage in the brain parenchyma. This study provides the first
      demonstration of the anatomical, metabolic and behavioral neuroprotective effects
      of MB in the striatum in vivo, and supports the notion that MB could be a
      valuable intervention against neural damage associated with oxidative stress and
      energy hypometabolism.

PMID- 19596059
TI  - A comparative study of top-down and bottom-up approaches for the preparation of
      micro/nanosuspensions.
AB  - Nano-sizing offers a promising method for the formulation of poorly aqueous
      soluble compounds. Nanosuspensions can be prepared by top-down or bottom-up
      approaches. The different conditions encountered in these two approaches can
      greatly affect nanosuspension characteristics. In this study, milling via
      microfluidization and precipitation via sonication were compared to study their
      effects on the formation and stability of ibuprofen nanosuspensions. Various
      stabilizers (SLS, PVP K-30, Pluronic F-68 and F-127, Tween 80 and different
      hydroxypropyl methylcelluloses (HPMCs)) were evaluated. Both processes resulted
      in a similar trend in the initial particle size and comparable short-term
      physical stability of suspensions. Of all the stabilizers investigated, the HPMCs
      were the most effective both in terms of particle size reduction and short-term
      physical stability. Differences in stabilizer efficacy were observed between the
      two processing methods. The initial particle size of the suspensions prepared
      using microfluidization correlated with the solubility of ibuprofen in the
      respective stabilizer solutions. Whereas, the initial particle size of
      suspensions prepared using precipitation under sonication correlated with the HLB
      values of the stabilizers. The solubility of ibuprofen in the stabilizer solution
      also played a significant role in the increase in particle size on storage,
      indicating Ostwald ripening.

PMID- 19596060
TI  - Embryonic stem cell-derived cardiomyocytes as a model system to study
      cardioprotective effects of dexamethasone in doxorubicin cardiotoxicity.
AB  - Embryonic stem cell (ESC)-derived beating cardiomyocytes may be considered as a
      suitable model for in vitro assessment of pharmacological and toxicological
      studies. In this model, laboratory animals are not required. In addition,
      physiological functions, such as heart beat, are assessed rather than single
      parameters such as cell viability. Here we report that doxorubicin (DOX)
      cardiotoxicity on mouse ESC-derived beating cardiomyocytes can be ameliorated by
      treatment with dexamethasone (DEX) when DEX is administrated only before DOX and
      not in combination with DOX. DEX effect appears to be mediated via glucocorticoid
      receptor and increases cardiomyocyte-specific gene expression. Cardiotoxicity of
      DOX can be augmented by calcium channel blocker, verapamil (VER) which also
      decreases the expression of cardiac gene markers. This model provides us with a
      clinical suggestion which proposes that the beneficial effect of DEX is obtained
      when DEX was added before DOX administration.

PMID- 19596061
TI  - Reactive oxygen species induced by beauvericin, patulin and zearalenone in CHO-K1
      cells.
AB  - The cytotoxic effects of mycotoxins, induction of reactive oxygen species (ROS)
      and generation of lipid peroxidation products in CHO-K1 cells were determined as
      function of increasing time of exposure and concentrations of beauvericin (BEA),
      patulin (PAT) and zearalenone (ZEA). The end points were evaluated after 24h of
      exposure, by the tetrazolium salt (MTT) and neutral red (NR) assays. The IC(50)
      values obtained on the MTT and NR assays ranged from 0.69 to 79.40 microM and
      4.40 to 108.76 microM, respectively. To determine the intracellular production of
      ROS, the intensity of fluorescence emitted from the probe H(2)-DCFDA was
      measured. The relative intensity of fluorescence from cells incubated with BEA,
      PAT and ZEA was approximately 4-, 7- and 4-fold higher in comparison with control
      cells at 0 min, respectively. Lipid peroxidation induced by ROS generation was
      assessed using the thiobarbituric acid reactive substances (TBARS) method for 2,
      24 and 48 h. The malondialdehyde (MDA) production was increased with BEA and PAT
      exposure in a concentration- and time-dependent manner. MDA was not increased
      after 1 and 5 microM ZEA exposures for 2h, but was slightly increased at 50
      microM. In conclusion, PAT was the most cytotoxic mycotoxin to CHO-K1 cells,
      followed by BEA and ZEA. Mycotoxins reduce cell viability correlated with the
      increases of ROS generation and MDA formation in concentration- and time
      dependent manner. These data suggested that cytotoxicity and ROS generation are
      mechanisms of mycotoxins mediated toxicity.

PMID- 19596063
TI  - Ischemia/reperfusion unveils impaired capacity of older adults to restrain
      oxidative insult.
AB  - Age independently predicts poor outcome in a variety of medical settings,
      including sepsis, trauma, severe burns, and surgery. Because these conditions are
      associated with oxidative stress, we hypothesized that the capacity to constrain
      oxidative insult diminishes with age, leading to more extensive oxidative damage
      during trauma. To test this hypothesis, we used suprasystolic inflation of an arm
      blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R)
      and quantified plasma F(2)-isoprostane (IsoP) levels in serial blood samples.
      Before I/R, IsoP levels were similar in young (20-33 years) and older adults (62
      81 years). After I/R challenge, the magnitude and duration of increased IsoP
      levels was significantly greater in older adults. Because aging is associated
      with declining levels of sex hormones that contribute to the regulation of
      antioxidant enzyme expression, we then examined the response to I/R in older
      women receiving hormone replacement therapy and found that these women did not
      manifest the amplified IsoP response found in untreated older women. These
      findings demonstrate that aging impairs the ability to restrain oxidative damage
      after an acute insult, which may contribute to the increased vulnerability of
      older adults to traumatic conditions and establishes a useful method to identify
      effective interventions to ameliorate this deficiency.

PMID- 19596064
TI  - Hydrogen peroxide down-regulates inositol 1,4,5-trisphosphate receptor content
      through proteasome activation.
AB  - Hydrogen peroxide (H(2)O(2)) is implicated in the regulation of signaling
      pathways leading to changes in vascular smooth muscle function. Contractile
      effects produced by H(2)O(2) are due to the phosphorylation of myosin light chain
      kinase triggered by increases in intracellular calcium (Ca(2+)) from
      intracellular stores or influx of extracellular Ca(2+). One mechanism for
      mobilizing such stores involves the phosphoinositide pathway. Inositol 1,4,5
      trisphosphate (IP(3)) mobilizes intracellular Ca(2+) by binding to a family of
      receptors (IP(3)Rs) on the endoplasmic-sarcoplasmic reticulum that act as ligand
      gated Ca(2+) channels. IP(3)Rs can be rapidly ubiquitinated and degraded by the
      proteasome, causing a decrease in cellular IP(3)R content. In this study we show
      that IP(3)R(1) and IP(3)R(3) are down-regulated when vascular smooth muscle cells
      (VSMC) are stimulated by H(2)O(2), through an increase in proteasome activity.
      Moreover, we demonstrate that the decrease in IP(3)R by H(2)O(2) is accompanied
      by a reduction in calcium efflux induced by IP(3) in VSMC. Also, we observed that
      angiotensin II (ANGII) induces a decrease in IP(3)R by activation of NADPH
      oxidase and that preincubation with H(2)O(2) decreases ANGII-mediated calcium
      efflux and planar cell surface area in VSMC. The decreased IP(3) receptor content
      observed in cells was also found in aortic rings, which exhibited a decreased
      ANGII-dependent contraction after treatment with H(2)O(2). Altogether, these
      results suggest that H(2)O(2) mediates IP(3)R down-regulation via proteasome
      activity.

PMID- 19596065
TI  - Significance of protein tyrosine kinase/protein tyrosine phosphatase balance in
      the regulation of NF-kappaB signaling in the inflammatory process and aging.
AB  - Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) are well
      recognized for the essential roles they play in signal transduction by
      maintaining proper balance under redox status. One of the major transcription
      factors known to be involved in aging is the redox-sensitive proinflammatory NF
      kappaB, which could be modulated by the activities of PTKs and PTPs. This study
      delved into a molecular inquiry of the PTK/PTP balance, which is affected by
      oxidative stress-induced redox changes during aging. To obtain the underlying
      molecular clues, we assessed the PTK/PTP status in the aged rat kidney utilizing
      aging-retarding calorie restriction and inflammation-triggering LPS paradigms.
      The results suggest that reactive species increase PTK activation, which is
      counterbalanced by decreased PTP, leading to a shift in the PTK/PTP balance. This
      shift in the balance was confirmed by free radical-generating AAPH injected into
      mouse or HEK293T cells, which led to NF-kappaB activation. To strengthen the
      findings, we perturbed the PTK/PTP balance using a PTP inhibitor, Na(3)VO(4),
      which caused NF-kappaB activation through phosphorylated NIK/IKK and MAPKs. Thus,
      our data suggest, for the first time, that the delicate balance between PTK and
      PTP is disturbed during aging and inflammation, both of which lead to NF-kappaB
      activation via NIK/IKK and MAPKs.

PMID- 19596062
TI  - Anatomy of a songbird basal ganglia circuit essential for vocal learning and
      plasticity.
AB  - Vocal learning in songbirds requires an anatomically discrete and functionally
      dedicated circuit called the anterior forebrain pathway (AFP). The AFP is
      homologous to cortico-basal ganglia-thalamo-cortical loops in mammals. The basal
      ganglia portion of this pathway, Area X, shares many features characteristic of
      the mammalian striatum and pallidum, including cell types and connectivity. The
      AFP also deviates from mammalian basal ganglia circuits in fundamental ways. In
      addition, the microcircuitry, role of neuromodulators, and function of Area X are
      still unclear. Elucidating the mechanisms by which both mammalian-like and unique
      features of the AFP contribute to vocal learning may help lead to a broad
      understanding of the sensorimotor functions of basal ganglia circuits.

PMID- 19596066
TI  - Mitochondrial dihydrolipoyl succinyltransferase deficiency accelerates amyloid
      pathology and memory deficit in a transgenic mouse model of amyloid deposition.
AB  - Mitochondrial dysfunction and oxidative stress are involved in Alzheimer disease
      (AD) pathogenesis. In human AD brains, the activity of the alpha-ketoglutarate
      dehydrogenase enzyme complex (alpha-KGDHC) is reduced. KGDHC is mostly involved
      in NADH production. It can also participate in oxidative stress and reactive
      oxygen species (ROS) production. The mitochondrial dihydrolipoyl
      succinyltransferase enzyme (DLST) is a key subunit specific to the alpha-KGDHC.
      In cultured cells, reduction of DLST increased H(2)O(2)-induced ROS generation
      and cell death. Thus, we asked whether partial genetic deletion of DLST could
      accelerate the onset of AD pathogenesis, using a transgenic mouse model of
      amyloid deposition crossed with DLST(+/-) mice. Tg19959 mice, which carry the
      human amyloid precursor protein with two mutations, develop amyloid deposits and
      progressive behavioral abnormalities. We compared Tg19959 mice to Tg19959-DLST(+/
      ) littermates at 2-3 months of age and studied the effects of DLST deficiency on
      amyloid deposition, spatial learning and memory, and oxidative stress. We found
      that alpha-KGDHC activity was reduced in DLST(+/-) mice. We also found that DLST
      deficiency increased amyloid plaque burden, Abeta oligomers, and nitrotyrosine
      levels and accelerated the occurrence of spatial learning and memory deficits in
      female Tg19959 mice. Our data suggest that alpha-KGDHC may be involved in AD
      pathogenesis through increased mitochondrial oxidative stress.

PMID- 19596067
TI  - Analysis of the mechanism by which tryptophan analogs inhibit human
      myeloperoxidase.
AB  - Myeloperoxidase (MPO) catalyzes the formation of oxidants that have been
      implicated in the pathogenesis of various diseases, including cardiovascular and
      pulmonary diseases and cancer. Inhibition of MPO oxidant-generating activity
      represents an attractive target for preventing the progression of inflammatory
      conditions. Peroxidation and chlorination catalytic activity were utilized to
      screen for the most effective tryptophan analog that inhibits MPO. Rapid kinetic
      measurements were performed to determine the mechanisms through which these
      compounds inhibit the catalytic activity of MPO. Substituents on the amino and
      carboxyl termini of tryptophan enhance its affinity toward MPO compared to a
      substituent on the indole ring. Hydrogen-bond donor capabilities and a positive
      charge on the amino group are not required for MPO inhibition. Hydroxyl
      containing indoles did not inhibit MPO H(2)O(2)-consumption activity. Elimination
      of the negative charge from the carboxyl terminus by introducing a hydrophobic
      character significantly enhanced tryptophan analog affinity for MPO and improved
      its inhibitory properties. Further mechanistic studies indicated that indole
      compounds inhibited MPO activity through the accumulation of compound II, an
      inactive MPO intermediate. Our results show that specific structural features of
      tryptophan analogs are involved in increasing the affinity for MPO and providing
      a significantly greater inhibition of MPO's catalytic activities.

PMID- 19596069
TI  - Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular
      disease and mortality--an update on patient populations with a wide range of
      cardiovascular risk.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      (NO) synthases. By inhibiting NO formation, ADMA causes endothelial dysfunction,
      vasoconstriction, elevation of blood pressure, and aggravation of experimental
      atherosclerosis. Cross-sectional studies in humans have revealed that ADMA plasma
      concentration is elevated in numerous populations with vascular diseases or at
      high cardiovascular risk. However, the potential causal relationship between
      elevated ADMA and cardiovascular events and mortality in humans can only be
      revealed in prospective clinical studies. This review gives an overview of
      currently available data from prospective clinical studies in which ADMA has been
      measured in populations at high, intermediate, or low global vascular risk.
      Although the analytical methods used to quantify ADMA varied and statistical
      approaches to assess the association of ADMA with risk differed, these data
      reveal that ADMA is significantly associated with an increased risk of incident
      cardiovascular events and total mortality in subjects at a broad range of global
      risk. Hazard ratios were mostly in a range comparable to that of traditional
      cardiovascular risk markers even after multivariable adjustments, suggesting that
      ADMA may be suitable as a diagnostic marker for risk assessment, and that the
      biochemical pathways that regulate ADMA may be promising therapeutic approaches
      to treat cardiovascular disease in the future.

PMID- 19596068
TI  - Hereditary inclusion body myopathy: a decade of progress.
AB  - Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, quadriceps
      sparing type commonly referred to as HIBM but also termed h-IBM or Inclusion Body
      Myopathy 2 (IBM2). The clinical manifestations begin with muscle weakness
      progressing over the next 10-20 years uniquely sparing the quadriceps until the
      most advanced stage of the disease. Histopathology of an HIBM muscle biopsy shows
      rimmed vacuoles on Gomori's trichrome stain, small fibers in groups and
      tubulofilaments without evidence of inflammation. In affected individuals
      distinct mutations have been identified in the GNE gene, which encodes the
      bifunctional enzyme uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) 2
      epimerase/N-acetyl-mannosamine (ManNAc) kinase (GNE/MNK). GNE/MNK catalyzes the
      first two committed steps in the biosynthesis of acetylneuraminic acid (Neu5Ac),
      an abundant and functionally important sugar. The generation of HIBM animal
      models has led to novel insights into both the disease and the role of GNE/MNK in
      pathophysiology. Recent advances in therapeutic approaches for HIBM, including
      administration of N-acetyl-mannosamine (ManNAc), a precursor of Neu5Ac will be
      discussed.

PMID- 19596071
TI  - Is cortical vasculature functionally organized?
AB  - The cortical vasculature is a well-structured and organized system, but the
      extent to which it is organized with respect to the neuronal functional
      architecture is unknown. In particular, does vasculature follow the same
      functional organization as cortical columns? In principle, cortical columns that
      share tuning for stimulus features like orientation may often be active together
      and thus require oxygen and metabolic nutrients together. If the cortical
      vasculature is built to serve these needs, it may also tend to aggregate and
      amplify orientation specific signals and explain why they are available in fMRI
      data at very low resolution.

PMID- 19596070
TI  - Cryo-electron tomography of nanoparticle transmigration into liposome.
AB  - Nanoparticle transport across cell membrane plays a crucial role in the
      development of drug delivery systems as well as in the toxicity response induced
      by nanoparticles. As hydrophilic nanoparticles interact with lipid membranes and
      are able to induce membrane perturbations, hypothetic mechanisms based on
      membrane curvature or hole formation have been proposed for activating their
      transmigration. We report on the transport of hydrophilic silica nanoparticles
      into large unilamellar neutral DOPC liposomes via an internalization process. The
      strong adhesive interactions of lipid membrane onto the silica nanoparticle
      triggered liposome deformation until the formation of a curved neck. Then the
      rupture of this membrane neck led to the complete engulfment of the nanoparticle.
      Using cryo-electron tomography we determined 3D architectures of intermediate
      steps of this process unveiling internalized silica nanoparticles surrounded by a
      supported lipid bilayer. This engulfing process was achieved for a large range of
      particle size (from 30 to 200 nm in diameter). These original data provide
      interesting highlights for nanoparticle transmigration and could be applied to
      biotechnology development.

PMID- 19596072
TI  - Robust Bayesian estimation of the location, orientation, and time course of
      multiple correlated neural sources using MEG.
AB  - The synchronous brain activity measured via MEG (or EEG) can be interpreted as
      arising from a collection (possibly large) of current dipoles or sources located
      throughout the cortex. Estimating the number, location, and time course of these
      sources remains a challenging task, one that is significantly compounded by the
      effects of source correlations and unknown orientations and by the presence of
      interference from spontaneous brain activity, sensor noise, and other artifacts.
      This paper derives an empirical Bayesian method for addressing each of these
      issues in a principled fashion. The resulting algorithm guarantees descent of a
      cost function uniquely designed to handle unknown orientations and arbitrary
      correlations. Robust interference suppression is also easily incorporated. In a
      restricted setting, the proposed method is shown to produce theoretically zero
      reconstruction error estimating multiple dipoles even in the presence of strong
      correlations and unknown orientations, unlike a variety of existing Bayesian
      localization methods or common signal processing techniques such as beamforming
      and sLORETA. Empirical results on both simulated and real data sets verify the
      efficacy of this approach.

PMID- 19596073
TI  - Effects of rodent prefrontal lesions on object-based, visual scene memory.
AB  - It has been suggested that certain prefrontal areas contribute to a neural
      circuit that mediates visual object memory. Using a successive go/no-go visual
      scene discrimination task, object-based long-term memory was assessed in two
      rodent prefrontal regions. Rewarded trials consisted of a standard scene of four
      toy objects placed over baited food wells. The objects and their locations
      composing the standard scene remained constant for the duration of the study.
      Trials in which one of the standard scene objects was replaced with a novel
      object were not rewarded. Following the establishment of a significant difference
      between latency to approach the rewarded standard scene compared to latency to
      approach non-rewarded scenes, quinolinic acid or control vehicle was infused into
      either the prelimbic and infralimbic cortices or the anterior cingulate cortex.
      Following a 1 week recovery period, subjects were retested. Animals with
      prelimbic/infralimbic cortex lesions displayed a profound and sustained deficit,
      whereas, animals with anterior cingulate cortex lesions showed a slight initial
      impairment but eventually recovered. Both lesion groups acquired a simple single
      object discrimination task as quickly as controls indicating that the deficits on
      the original scene discrimination task were not due to motivational, response
      inhibition, or perceptual problems.

PMID- 19596074
TI  - Transcriptional profiling for Aspergillusnidulans HogA MAPK signaling pathway in
      response to fludioxonil and osmotic stress.
AB  - In filamentous fungi, the His-Asp phosphorelay signaling system and HOG pathway
      are involved in the action of the fungicides, fludioxonil, and iprodione, as well
      as osmotic and oxidative stress responses. Aspergillusnidulans response
      regulators (RRs), SskA and SrrA, and histidine kinase (HK), NikA, are involved in
      the growth inhibitory effects of these fungicides. To gain further insights into
      the molecular basis for these signaling systems, we performed DNA microarray
      analyses of fludioxonil and osmotic stress responses in A.nidulans. A global
      expression analysis revealed that a large number of genes were modulated by
      fludioxonil treatment in an SskA-dependent manner, whereas SrrA hardly
      contributed to this modulation. The fludioxonil up-regulated or down-regulated
      genes (FUGs or FDGs, respectively) are also dependent on the HogA MAPK cascade.
      We found that the SskA-HogA pathway regulates expression of atfA gene encoding a
      transcription factor involved in conidia stress tolerance. From the results of
      microarray analyses, AtfA-dependent FUGs largely overlapped with HogA-dependent
      FUGs, suggesting that AtfA functions downstream of the HogA MAPK. A series of
      microarray analyses showed that the inferred SskA-HogA-AtfA pathway is implicated
      in the transcriptional response to osmotic stress as well as fludioxonil. The
      srrAatfA null double mutant turns off the SrrA and SskA-HogA-AtfA pathways and
      showed sensitivity to osmotic stress but no resistance to fludioxonil. Our data
      revealed that the growth inhibitory effect of fludioxonil depends on factors
      other than AtfA in spite of the fact that AtfA functions downstream of the HogA
      MAPK cascade. The complexity of the stress response in the His-Asp phosphorelay
      system followed by the HogA MAPK cascade is discussed.

PMID- 19596075
TI  - Heart rate as a sublethal indicator of thermal stress in juvenile freshwater
      mussels.
AB  - Freshwater mussels (Unionoida) are one of the most sensitive and rapidly
      declining faunal groups in the world. Rising water temperatures, caused by
      industrial discharges, land development, or climate change can further challenge
      threatened unionid communities. The direct relationship between heart rate and
      temperature in ectotherms enables the use of heart rate as an indicator of whole
      animal thermal stress. The purpose of this study was to assess the utility of
      heart rate as an indicator of thermal stress in freshwater mussels. Seven species
      of juvenile mussels (Lampsilis siliquoidea, Potamilus alatus, Ligumia recta,
      Ellipsaria lineolata, Megalonaias nervosa, Alasmidonta varicosa, and Villosa
      delumbis) were evaluated in response to a range of experimental temperatures (20
      36 degrees C) at three acclimation temperatures (17, 22, and 27 degrees C). Heart
      rate was measured by direct visual observation through transparent mussel shells.
      The average heart rate for all 7 species at 20 degrees C was 55bpm, with a range
      from 38bpm (L. recta) to 65bpm (P. alatus). L. recta and V. delumbis exhibited
      significant changes in heart rate with increasing temperature at each of the
      three acclimation temperatures. The use of heart rate appears to be a suitable
      indicator of thermal stress in some unionid mussels.

PMID- 19596076
TI  - A neural analysis of avoidance conditioning with the feeding attractant glycine
      in Pleurobranchaea japonica.
AB  - Glycine (Gly) is one of the amino acids that most strongly provoke feeding
      behavior in the carnivorous opisthobranch sea slug Pleurobranchaea japonica.
      Placing of an aliquot of a Gly solution in front of the anterior end of this
      animal induced feeding responses such as orientation to the origin of the
      stimulus and extrusion of the proboscis. In contrast, light stimulation of the
      body of the animal with a glass-fiber light guide evoked aversive responses
      involving the gill withdrawal response. Animals were trained by pairing a Gly
      solution stimulus (conditioned) and a light stimulus (unconditioned). After
      training with repetitive paired stimuli, we found that animals exhibited aversive
      responses to the Gly solution. We confirmed achievement of a conditioned Gly
      aversive reflex in intact animals by recording of motor impulses with an
      electrode implanted on the branchial nerve responsible for the gill withdrawal
      response, the most reliable index of the reflex. Motor discharge of the branchial
      nerve associated with the conditioned Gly-aversive reflex persisted even in a
      preparation isolated from an animal which had previously acquired the reflex.
      This study provides an experimental model for neural analysis with in vivo long
      term nerve recording using an electrode implanted in a nerve of an intact animal
      for neuroethological training.

PMID- 19596077
TI  - Osmoregulatory responses of expression of vasotocin, isotocin, prolactin and
      growth hormone genes following hypoosmotic challenge in a stenohaline marine
      teleost, tiger puffer (Takifugu rubripes).
AB  - To examine possible roles of vasotocin (VT), isotocin (IT), prolactin (PRL) and
      growth hormone (GH) in osmoregulation of a stenohaline marine teleost, tiger
      puffer (Takifugu rubripes), changes in expression levels of these genes following
      hypoosmotic challenge, were examined in two experiments. Fish were transferred
      from 100% seawater (SW) to 33% SW, 10% SW and fresh water (FW), and left for
      3days in experiment I. In experiment II, fish were transferred to FW, and left
      for 1day. Changes in plasma osmolality, concentrations of Na(+) and Cl(-), and
      Na(+)/K(+)-ATPase activity in the gills and kidney were examined. Changes in the
      absolute amounts of VT, IT, PRL and GH mRNAs were determined by real-time PCR. In
      experiment I, almost all fish survived over 3days of acclimation. The plasma
      parameters decreased on day 1, and remained at similar levels until day 3. The
      renal Na(+)/K(+)-ATPase activity significantly increased in 10% SW and FW on day
      1. The amounts of VT and IT mRNAs tended to decrease in the hypoosmotic
      conditions on day 1. The amounts of PRL mRNA significantly increased in the
      hypoosmotic conditions, whereas those of GH mRNA decreased in FW. In experiment
      II, the amount of VT mRNA significantly decreased in FW concomitantly with the
      changes in PRL and GH mRNAs. The present results suggest that the hyperosmotic
      responses may be regulated by neuroendocrine factors such as VT, PRL and GH in
      tiger puffer, as in case of euryhaline teleosts. Particularly, the present study
      first shows that the expression of VT gene may be down-regulated following
      hypoosmotic challenge in the stenohaline marine fish.

PMID- 19596078
TI  - Functional analysis of Foxp3 and CTLA-4 expressing HTLV-1-infected cells in a rat
      model.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T
      cell leukemia (ATL). Some ATL cells express Foxp3, which is known as regulatory T
      cell (Treg cell) specific transcription factor. It is suggested that Treg cell
      like suppressive activity of Foxp3 expressing ATL cells is associated to ATL
      development and related immunodeficiency. To develop an HTLV-1 model system that
      enables to investigate the association of Treg function in ATL progression, we
      examined the expression of Foxp3 and CTLA-4, Treg cell-associated factor, in
      established HTLV-1-infected rat cell lines and their regulatory function. We
      found the expression of Foxp3 in 10 of 22 and CTLA-4 in 10 of 19 HTLV-1-infected
      rat cell lines. Moreover, some of the Foxp3 and/or CTLA-4 expressing cell lines
      suppressed proliferation of naive T cells that were stimulated with anti-CD3
      antibody. Particularly all Foxp3(+) CTLA-4(+) cells showed the suppressive
      activity. Our data suggest the usefulness of our rat model systems for further
      analysis of the role of Treg cell-associated factors on the development of ATL
      and related immunodeficiency in vivo.

PMID- 19596079
TI  - Revealing promiscuous drug-target interactions by chemical proteomics.
AB  - The (poly-)pharmacological activities of a drug can only be understood if its
      interactions with cellular components are comprehensively characterized. Mass
      spectrometry-based chemical proteomics approaches have recently emerged as
      powerful tools for the characterization of drug-target interactions in samples
      from cell lines and tissues. At the same time, off-target activities can be
      identified. This information can contribute toward optimization of candidate drug
      molecules and reduction of side effects. In this review, we describe recent
      advances in chemical proteomics and outline potential applications in drug
      discovery.

PMID- 19596080
TI  - Understanding autoimmune disease: new targets for drug discovery.
AB  - A more complete understanding of the mechanisms that drive autoimmune diseases
      has begun to be translated into therapeutic options with significant clinical
      consequences. A clear example of this is the introduction of biological
      therapies, which have provided new therapeutic avenues, as well as validated the
      mediators (TNFalpha, IL-6), mechanisms (T cell costimulation, leukocyte
      migration), and cellular players (T and B lymphocytes) of the disease process
      itself. New discoveries into the role of Th17 and regulatory T cells and the
      epigenetic regulation of cytokine expression may offer novel intervention
      strategies to satisfy the unmet medical needs that still exist in these diseases.

PMID- 19596081
TI  - 'OnePoint'--combining OneNote and SharePoint to facilitate knowledge transfer.
AB  - The identification and development of novel drugs requires a multidisciplinary
      team of individuals whose membership changes during the lifecycle of a project.
      Incomplete knowledge transfer across this team can be a barrier to effective
      decision-making and efficient drug discovery. We have deployed a new
      infrastructure supporting information storage and distribution within small teams
      using Microsoft's SharePoint server technology in conjunction with the desktop
      application OneNote. This delivers a user-friendly collaborative workspace that
      is fast, flexible and carries a low training burden. Demand from drug project
      teams for this 'solution' has now resulted in site-wide deployment to over 500
      people across research.

PMID- 19596082
TI  - In vivo modulation of immune response and antioxidant defense in Atlantic cod,
      Gadus morhua following oral administration of oxolinic acid and florfenicol.
AB  - Oxolinic acid and florfenicol are the commonly used antibiotics for the treatment
      of bacterial diseases in Atlantic cod, Gadus morhua. The changes in selected
      innate humoral immune response of the fish, bacterial proliferation in serum and
      transcriptional activity of selected immune and antioxidant defense-related genes
      following oral administration of these antimicrobial compounds were evaluated.
      Juvenile cod (75-100 g) were fed commercial feed coated with either florfenicol
      (10 mg kg(-1) fish, active ingredient) or oxolinic acid (20 mg kg(-1) fish,
      active ingredient) at a ration of 0.5% body weight for 10 days. Whole blood and
      serum samples were collected on the 10th day of feeding the antibiotics and at 3,
      5 and 10 days after their withdrawal. Serum protein was significantly higher in
      fish at the 10th day post-withdrawal of both antibiotics. Florfenicol-fed fish
      had lower myeloperoxidase activity at 3 days post-withdrawal, while there were
      differential effects on alkaline phosphatase activity. Vibrio anguillarum and
      Aeromonas salmonicida were significantly reduced in the sera of antibiotics-fed
      fish until the 5th day post-withdrawal. Florfenicol could inhibit V. anguillarum
      better than oxolinic acid, while A. salmonicida was more susceptible than V.
      anguillarum upon treatment with both antibiotics. Furthermore, transcriptional
      profiles of selected genes related to bacterial defense, inflammation and
      antioxidant defense were dependent on the type of antibiotics that was
      administered and the time of sampling. These results indicate that oral
      administration of antibiotics modulates the immune response and antioxidant
      defense in Atlantic cod and these may, in turn, affect their ability to resist
      bacterial pathogens.

PMID- 19596083
TI  - Differential expression of Rfx1-4 during mouse spermatogenesis.
AB  - The regulatory factor X (RFX) family of transcription factors has been recently
      implicated in gene regulation during spermatogenesis. However, the relative
      expression of individual members during this developmental process is not
      completely characterized, particularly in the case of Rfx4, which has multiple
      transcript variants in the testis. We used reverse transcriptase-dependent real
      time PCR, 5'-RACE cloning, and Western blotting to compare transcripts and
      protein levels for this family in cell populations from the three major phases of
      spermatogenesis (mitotic, meiotic, and haploid). Transcripts for Rfx1-4 were
      present at trace to low levels in spermatogonia prepared from 8-day-old mice.
      Transcripts for both Rfx2 and Rfx4 were elevated in mid-late pachytene
      spermatocytes; however, the dominant Rfx4 transcript present begins at a
      downstream exon and lacks the DNA binding domain. Transcripts for all four genes
      were elevated in early haploid cells (round spermatids). In these cells Rfx4
      transcripts originate primarily from a newly described promoter with intron 1 but
      are expected to be translationally compromised due to a poorly situated start
      codon. Western blotting confirmed that RFX2 is greatly elevated beginning in
      meiosis and also confirmed that full-length RFX4 protein is not prevalent in
      mouse testis at any stage. These results imply that RFX2 is the most likely X box
      binding factor to influence novel gene expression during meiosis, that RFX1-3 may
      all play roles in haploid cells but that RFX4 is much less prevalent than implied
      by its high transcript levels.

PMID- 19596084
TI  - Longitudinal study of beta2-microglobulin abnormalities in schizophrenia.
AB  - In an earlier cross-sectional study, we reported antipsychotic-naive
      schizophrenia patients to have significantly elevated beta2-microglobulin
      (beta2M) level suggestive of its potential association with the pathogenesis of
      schizophrenia. In this study, we present the follow-up analyses of beta2M in 31
      patients from the previous study who were re-assessed after 92.1+/-7.2 days of
      antipsychotic treatment. Compared to baseline, there was a further significant
      elevation of beta2M in schizophrenia patients following treatment, especially in
      those who were treated with risperidone. Also, there was a significant negative
      correlation between beta2M level and total psychopathology score during follow-up
      in risperidone group. The study findings extend further support the role for
      beta2M in the pathogenesis of schizophrenia strengthening the case for immune
      dysregulation. Moreover, the observations suggest the possibility that the
      mechanism of action of antipsychotics might involve alteration of immune
      parameters.

PMID- 19596085
TI  - A robust in vitro screening assay to identify NF-kappaB inhibitors for
      inflammatory muscle diseases.
AB  - Specific therapies are not available for inflammatory muscle diseases. We and
      others have shown that the pro-inflammatory NF-kappaB pathway is highly activated
      in these conditions. Since NF-kappaB is an important therapeutic target, we
      decided to utilize an in vitro screening assay to identify potential inhibitors
      that block TNF-alpha induced NF-kappaB activation in a C2C12 muscle line stably
      expressing an NF-kappaB luciferase reporter gene. Upon evaluation of multiple
      anti-inflammatory agents in undifferentiated myoblasts as well as differentiated
      myotubes , we found different levels of inhibition depending on the state of
      differentiation. Interestingly, we found that some drugs that are known to
      inhibit NF-kappaB in immune cells were not effective in muscle cells. Drug
      toxicity was assessed for using an MTT cell viability assay, and the validity of
      the luciferase assay was verified by immunostaining for NF-kappaB nuclear
      translocation in myoblasts. In conclusion, we have determined the optimal assay
      conditions for detecting potentially valuable NF-kappaB inhibitors for the first
      time in a muscle cell line that may have significant therapeutic potential for
      inflammatory muscle diseases.

PMID- 19596086
TI  - The origin of Listeria monocytogenes 4b isolates is signified by subproteomic
      profiling.
AB  - Among the 13 known serovars of Listeria monocytogenes, strains exhibiting the
      serovar 4b are the most prevalently involved in epidemics of human listeriosis.
      The molecular reasons for the major involvement of serovar 4b strains in all
      major foodborne outbreaks in contrast to the lower prevalence of this serovar
      among food isolates remain indefinite. In order to provide further insight in the
      protein expression of L. monocytogenes 4b strains, the cytoplasmic and
      extracellular proteomes of L. monocytogenes 4b strains from different origins,
      i.e. environmental, clinical and asymptomatical carriage, were investigated by
      two-dimensional gel electrophoresis. Statistical hierarchical clustering analysis
      on subproteomic profiles clearly discriminated the strains according to their
      origin. Protein spots differentiating the subproteome patterns were identified
      using MALDI-TOF MS through their peptide mass fingerprint.

PMID- 19596087
TI  - Amyloid fibrils formed by selective N-, C-terminal sequences of mouse
      apolipoprotein A-II.
AB  - In mice, amyloidogenic type C apolipoprotein A-II (apoA-II) forms amyloid fibrils
      in age-associated amyloidosis. To understand the mechanism of amyloid fibril
      formation by apoA-II, we examined the polymerization of synthetic partial
      peptides of apoA-II in vitro. None of the partial apoA-II peptides polymerized
      into amyloid fibrils when tested as a single species mixture. We found a unique
      mechanism in which N- and C-terminal peptides associated into amyloid fibrils in
      a 1:1 ratio at pH 2.5. The 11-residue amino acid sequence (6-16), which is a
      common sequence of type B apoA-II and type C apoA-II proteins in amyloidosis
      resistant mice and amyloidosis-susceptible mice, respectively, was critical for
      polymerization into amyloid fibrils. The 18-residue-long amino acid sequence (48
      65) is also necessary for nucleation, but not for the extension phase. These
      findings suggest that there may be different mechanisms underlying the nucleation
      and extension phases of apoA-II amyloid fibril formation. We also found that
      amino acid substitutions between type B apoA-II (Pro5, Val38) and type C apoA-II
      (Gln5, Ala38) did not affect either phase. The strategy of using synthetic
      partial peptides of amyloidogenic proteins in vitro is a useful system for
      understanding amyloid fibril formation and for the development of novel
      therapies.

PMID- 19596088
TI  - Dynamical transition in a large globular protein: Macroscopic properties and
      glass transition.
AB  - Hydrated soy-proteins display different macroscopic properties below and above
      approximately 25% moisture. This is relevant to the food industry in terms of
      processing and handling. Quasi-elastic neutron spectroscopy of a large globular
      soy-protein, glycinin, reveals that a similar moisture-content dependence exists
      for the microscopic dynamics as well. We find evidence of a transition analogous
      to those found in smaller proteins, when investigated as a function of
      temperature, at the so-called dynamical transition. In contrast, the glass
      transition seems to be unrelated. Small proteins are good model systems for the
      much larger proteins because the relaxation characteristics are rather similar
      despite the change in scale. For dry samples, which do not show the dynamical
      transition, the dynamics of the methyl group is probably the most important
      contribution to the QENS spectra, however a simple rotational model is not able
      to explain the data. Our results indicate that the dynamics that occurs above the
      transition temperature is unrelated to that at lower temperatures and that the
      transition is not simply related to the relaxation rate falling within the
      spectral window of the spectrometer.

PMID- 19596090
TI  - Influence of the bonding substrate in dental composite polymerization stress
      testing.
AB  - Our objective was to compare the polymerization stress (sigma(pol)) of a series
      of composites obtained using poly(methyl methacrylate) (PMMA) or glass as bonding
      substrates, and to compare the results with those from in vitro microleakage of
      composite restorations. The tested hypothesis was that stress values obtained in
      a less rigid testing system (i.e. using PMMA) would show a better relationship
      with microleakage data. Five dental composites were tested: Filtek Z250 (FZ),
      Z100 (Z1), Concept (CO), Durafill (DU) and Heliomolar (HM). sigma(pol) was
      determined in 1mm high specimens inserted between two rods (O=5mm) of either PMMA
      or glass. The composite elastic modulus (E) was obtained by three-point bending.
      sigma(pol) and E data were submitted to a one-way analysis of variance/Tukey test
      (alpha=0.05). For the microleakage test (MI), bovine incisors received
      cylindrical cavities (O=5mm, h=2mm), which were restored in bulk. After storage
      for 24h in water, specimens were subjected to dye penetration using AgNO(3) as
      tracer. Specimens were sectioned twice, perpendicularly, and microleakage was
      measured (in millimeters) under 20x magnification. Data from MI were submitted to
      the Kruskal-Wallis test. Means (SD) of sigma(pol) (MPa) using glass/PMMA were FZ:
      7.5(1.8)(A)/2.5(0.2)(bc); Z1: 7.3(0.5)(A)/2.8(0.3)(ab); CO:
      6.8(1.1)(A)/3.2(0.5)(a); DU: 4.5(0.7)(B)/2.0(0.2)(bc); HM:
      3.5(0.2)(B)/2.3(0.3)(c). sigma(pol) obtained using PMMA rods were 34-67% lower
      than with glass. Means (SD) for tooth average/tooth maximum microleakage were FZ:
      0.92(0.19)(B)/1.53(0.30)(a); Z1: 1.19(0.21)(A)/1.75(0.20)(a); CO:
      1.26(0.25)(A)/1.78(0.24)(a); DU: 0.83(0.30)(B)/1.68(0.46)(a); HM:
      0.81(0.27)(B)/1.64(0.54)(a). The tested hypothesis was confirmed, as the
      composites showed the same ordering both in the polymerization stress test using
      PMMA rods and in the microleakage test.

PMID- 19596091
TI  - In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug
      controlled release matrices.
AB  - In order to find a new way to slow down the release of drugs and to solve the
      burst release problem of drugs from traditionally used hydrogel matrices, a
      series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite
      beads was prepared by the in situ generation of HA micro-particles in the beads
      during the sol-gel transition process of SA. The SA/HA nanocomposites were
      characterized by Fourier transform IR spectroscopy, X-ray fluorescence
      spectrometry, scanning electron microscopy and field emission SEM in order to
      reveal their composition and surface morphology as well as the role that the in
      situ generated HA micro-particles play. The factors influencing the swelling
      behavior, drug loading and controlled release behavior of the SA/HA nanocomposite
      beads were also investigated using diclofenac sodium (DS) as the model drug. The
      HA micro-particles act as inorganic crosslinkers in the nanocomposites, which
      could contract and restrict the movability of the SA polymer chains, and then
      change the surface morphology and decrease the swell ratio. Meanwhile, the
      entrapment efficiency of DS was improved, and the burst release of DS was
      overcome. The factors (including concentration of Ca(2+), reaction time and
      temperature) affecting the growth of HA micro-particles have a clear influence on
      the entrapment efficiency and release rate of DS. In this work, the nanocomposite
      beads prepared under optimum condition could prolong the release of DS for 8h
      more compared with the pristine SA hydrogel beads.

PMID- 19596092
TI  - Fabrication of novel hepatoma-targeting microdisks by hydrogen bond-assisted self
      assembly of an azacitidine-conjugating amphiphilic random copolymer.
AB  - Novel hepatoma-targeting azacitidine-conjugating microdisks were successfully
      fabricated by hydrogen bond-assisted self-assembly of an amphiphilic random
      copolymer with galactose and azacitidine as pendants, poly(5'-O-vinyladipyl
      azacitidine-co-6-O-vinylsebacyl-galactose). The random copolymer was easily
      prepared by a two-step chemoenzymatic synthetic route, and the possibility of its
      self-assembly was verified by ultraviolet-visible and fluorescence spectroscopy
      using pyrene as the hydrophobic probe. Transmission electron microscopy and
      scanning electron microscopy indicated that aggregation morphologies of these
      self-assemblies were thin disks with radii from 250 to 500nm. Section analysis of
      atomic force microscopy for a thin disk gave a thickness of approximately 16nm.
      The existence of hydrogen bonds among the pendants was investigated by infrared
      spectra and Gaussian calculation. Cellular uptake assay observed by confocal
      laser scanning microscopy and cell cytotoxicity tests by MTT dye reduction method
      showed that the self-assemblies had an evident hepatoma-targeting function to
      hepG2 human hepatoma cells and could effectively realize cellular internalization
      of azacitidine.

PMID- 19596089
TI  - Terminal deoxynucleotidyl transferase: the story of a misguided DNA polymerase.
AB  - Nearly every DNA polymerase characterized to date exclusively catalyzes the
      incorporation of mononucleotides into a growing primer using a DNA or RNA
      template as a guide to direct each incorporation event. There is, however, one
      unique DNA polymerase designated terminal deoxynucleotidyl transferase that
      performs DNA synthesis using only single-stranded DNA as the nucleic acid
      substrate. In this chapter, we review the biological role of this enigmatic DNA
      polymerase and the biochemical mechanism for its ability to perform DNA synthesis
      in the absence of a templating strand. We compare and contrast the molecular
      events for template-independent DNA synthesis catalyzed by terminal
      deoxynucleotidyl transferase with other well-characterized DNA polymerases that
      perform template-dependent synthesis. This includes a quantitative inspection of
      how terminal deoxynucleotidyl transferase binds DNA and dNTP substrates, the
      possible involvement of a conformational change that precedes phosphoryl
      transfer, and kinetic steps that are associated with the release of products.
      These enzymatic steps are discussed within the context of the available
      structures of terminal deoxynucleotidyl transferase in the presence of DNA or
      nucleotide substrate. In addition, we discuss the ability of proteins involved in
      replication and recombination to regulate the activity of the terminal
      deoxynucleotidyl transferase. Finally, the biomedical role of this specialized
      DNA polymerase is discussed focusing on its involvement in cancer development and
      its use in biomedical applications such as labeling DNA for detecting apoptosis.

PMID- 19596094
TI  - Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy.
AB  - The synthesis, characterization and property evaluation of drug-loaded polymer
      coated magnetic nanoparticles (MNPs) relevant to multimodal cancer therapy has
      been studied. The hyperthermia and controlled drug release characteristics of
      these particles was examined. Magnetite (Fe(3)O(4))-poly-n-(isopropylacrylamide)
      (PNIPAM) composite MNPs were synthesized in a core-shell morphology by dispersion
      polymerization of n-(isopropylacrylamide) chains in the presence of a magnetite
      ferrofluid. These core-shell composite particles, with a core diameter of
      approximately 13nm, were loaded with the anti-cancer drug doxorubicin (dox), and
      the resulting composite nanoparticles (CNPs) exhibit thermoresponsive properties.
      The magnetic properties of the composite particles are close to those of the
      uncoated magnetic particles. In an alternating magnetic field (AMF), composite
      particles loaded with 4.15 wt.% dox exhibit excellent heating properties as well
      as simultaneous drug release. Drug release testing confirmed that release was
      much higher above the lower critical solution temperature (LCST) of the CNP, with
      a release of up to 78.1% of bound dox in 29h. Controlled drug release testing of
      the particles reveals that the thermoresponsive property can act as an on/off
      switch by blocking drug release below the LCST. Our work suggests that these dox
      loaded polymer-coated MNPs show excellent in vitro hyperthermia and drug release
      behavior, with the ability to release drugs in the presence of AMF, and the
      potential to act as agents for combined targeting, hyperthermia and controlled
      drug release treatment of cancer.

PMID- 19596093
TI  - A novel thermosensitive polymer with pH-dependent degradation for drug delivery.
AB  - A class of thermosensitive biodegradable multiblock copolymers with acid-labile
      acetal linkages were synthesized from Pluronic triblock copolymers (Pluronic P85
      and P104) and di-(ethylene glycol) divinyl ether. The novel polymers were
      engineered to form thermogels at body temperature and degrade in an acidic
      environment. The Pluronic-based acid-labile polymers were characterized using
      nuclear magnetic resonance, gel permeation chromatography and differential
      scanning calorimetry. In vitro biocompatibility of the synthesized polymers was
      evaluated using calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay. The polymers showed reverse thermogelling behavior in
      water around body temperature. The sol-gel transition temperatures of the
      polymers synthesized from Pluronic P85 and P104 were lowered from 70.3 to 30
      degrees C and from 68.5 to 26.9 degrees C, respectively, when the synthesized
      polymers were compared with corresponding Pluronic block copolymers at a
      concentration of 25wt.%. The hydrophobic dye solubilization confirmed the
      formation of polymeric micelles in the aqueous solution. The sizes of the
      multiblock copolymers increased on a rise in temperature, indicating that thermal
      gelation was mediated by micellar aggregation. The thermally driven hydrogels
      showed preferential polymer degradation at acidic pH. At pH 5.0 and 6.5, the
      release of 40kDa fluorescein isothiocyanate-dextran (FITC-dextran) from the
      thermally formed hydrogels was completed within 2 and 9 days, respectively.
      However, FITC-dextran was continuously released up to 30 days at neutral pH. The
      mechanism of FITC-dextran release at pH 5.0 was mainly an acid-catalyzed
      degradation, whereas both diffusion and pH-dependent degradation resulted in FITC
      dextran release at pH 6.5. The novel polymers hold great potential as a pH
      sensitive controlled drug delivery system owing to their interesting phase
      transition behavior and biocompatibility.

PMID- 19596095
TI  - [About the bioethics' law].

PMID- 19596096
TI  - Pathophysiological mechanisms and consequences of cardiovascular calcifications:
      role of uremic toxicity.
AB  - SUMMARY: Chronic kidney disease (CKD) represents an accelerated model of the
      active cardiovascular calcification process. Recent data from our laboratory
      indicate the presence of a possible vascular remodeling leading to vascular
      calcification similar to that observed in bone tissue, and emphasize the role of
      uremic toxicity. Uremic serum not only induces differentiation of smooth muscle
      cells into an osteoblast-like phenotype but also inhibits the differentiation of
      monocyte-macrophages cells into osteoclasts. The imbalance between the two
      processes in vascular walls in favor of osteoblast-like formation could lead to
      calcification. Cardiovascular calcification may contribute to the high rate of
      cardiovascular disease in patients with CKD. However, uremic toxicity, which
      participates in the pathogenesis of cardiovascular calcification, seems to have
      independent effects on vascular walls, at least in the early stages of CKD. We
      recently reported that functional (i.e. endothelial dysfunction) rather than
      structural changes, including vascular calcification, may contribute to the
      aortic hemodynamic changes observed during early CKD. Uremic toxicity also
      appears to be associated with calcification of intracranial arteries. Knowledge
      concerning the pathogenesis and consequences of cardiovascular calcification
      derived from the uremic model therefore opens up new perspectives for
      pharmacologic treatments that may also help to prevent and/or treat
      cardiovascular calcification, and consequently cardiovascular mortality and
      morbidity, not only in CKD patients but also in the general population.

PMID- 19596098
TI  - [Schizophrenia, a neurodevelopmental illness].
AB  - SUMMARY: Developmental anomalies have been identified as risk factors for a
      future schizophrenic illness: low weight at birth, congenital malformations,
      delayed motor and social learning. Cognitive deficits and neurological soft signs
      belong to the indices of the schizophrenic spectrum. Neuroimaging has visualized
      various structural abnormalities present from the very beginning of
      schizophrenia. These structural changes may represent an exacerbation of normal
      neurodevelopmental processes. Moreover, vulnerability genes for schizophrenia are
      involved at different stages of neurodevelopment: the best studied associations
      are dysfunctional variants of DISC-1 and neuroregulin-1 genes, the role of other
      genes (dysbindin, BDNF, reelin...) remaining more widely debated. Lastly, the
      observation of structural chromosomal anomalies in 15% of patients suffering from
      schizophrenia (versus 5% of controls), more frequent in early onset schizophrenia
      (32% of cases) suggests a neurodevelopmental cause. Such a dynamic understanding
      of schizophrenia is consistent with what we know about cerebral plasticity along
      the life span. This does not preclude the search for cues of degenerative
      mechanisms. The issue now is a better characterization of the vulnerable
      phenotype for screening procedures to be implemented prior to disease onset.

PMID- 19596097
TI  - [Separation of chiral pharmaceutical drugs by chromatographic and electrophoretic
      techniques].
AB  - SUMMARY: A large number of pharmaceutical drugs possess one or more centers of
      asymmetry giving rise to enantiomers whose pharmacological properties and
      toxicity are often different. At successive stages of drug discovery, the
      enantiomers of any chiral molecule must be isolated and analyzed and their
      enantiomeric purity determined. The electrophoretic and chromatographic
      techniques have become the most important tools to routinely determine the
      enantiomeric purity of pharmaceutical molecules. Liquid chromatography (LC) is
      the most widely used because of the large number of columns marketed, the variety
      of selectivities available and the ease at which analytical results can be scaled
      up to the preparative level. In particular, more than 80% of enantioseparations
      of pharmaceutical molecules are successful with polysaccharide-derivative
      stationary phases (cellulose, amylose) for multiple system solvents (normal
      phase, polar organic phase or reverse phase). Complementary selectivities can be
      achieved more rapidly with other types of stationary phase (glycopeptides,
      Pirkle, cyclodextrins) but their application is hindered by problems of stability
      (proteins) or transfer to the preparative scale (cyclodextrins). At the present
      time, glycopeptide phases offer very promising prospects for the separation of
      amino acids (and derivatives) and peptide enantiomers. In addition, because of
      its faster analysis and environmental benefits, supercritical chromatography
      (SFC) has given rise to renewed interest. Capillary electrophoresis (CE) is an
      orthogonal technique complementary to chromatographic methods. Its principle
      involves the formation of diastereoisomer complexes after addition of anionic (HS
      beta-CD, HS-gamma-CD CM-beta-CD) or neutral (TM-beta -CD, HP-beta-CD, DM-beta-CD,
      HP-gamma-CD) cyclodextrins to the running buffer. Compared to LC, CE analyses are
      cheaper (no chiral column, no solvent, low consumption of chiral selector) and
      peak efficiencies are higher by one order of magnitude. Furthermore, the
      mechanism of separation in CE is much simpler to understand and predict. However,
      the low capacity of CD column prevents its use at the preparative scale and
      consequently hampers its development as an analytical technique. Today, the
      increasing number of new drug candidate molecules produced daily, and for which
      the determination of enantiomeric purity is required before further development,
      encourages the pharmaceutical industry to seek fast chiral analysis methods based
      on simple protocols. The speed of analysis is more important than resolution.
      Thus, screening strategies are implemented with HPLC, SFC and CE including the
      selection of a limited number of chiral selectors with strong powers of chiral
      recognition.

PMID- 19596100
TI  - [Study of variability in response to aspirin and clopidogrel: clinical and/or
      biological resistance?].
AB  - Millions of people in France are taking long-term treatments with the two main
      antiplatelet drugs, aspirin and/or clopidogrel. Most of these people are on a
      secondary preventive regimen after arterial thrombotic events such as myocardial
      infarction, stroke, or ischemic complications of lower limb arteriopathy. The
      term resistance is often a source of confusion. When used, its definition should
      be explicit. It would be probably be wiser to use a term such as "variable
      response" which is more widely accepted by specialists and researchers. It would
      be better to use the term variable platelet response since true pharmacological
      resistance is rare. The distinction may have clinical pertinence in terms of
      prognosis. An abundant amount of biological and clinical work in the literature
      has improved our understanding of the topic. Diverse tests for exploring platelet
      functions can be used to evaluate the biological impact of treatment. They
      should, in the near future, contribute to the implementation of guidelines or
      suggestions for optimal therapeutic modalities. Upcoming results of ongoing large
      scale prospective studies will be needed before confirming the potential
      usefulness and clinical pertinence of these tests.

PMID- 19596099
TI  - [Resolution of chiral molecules of pharmaceutical interest by means of
      preferential crystallization].
AB  - SUMMARY: Various aspects of the chiral discrimination in the solid state are
      examined. The interests of the conglomerate are illustrated by two applications:
      the preparative enantiomeric purification and the preferential crystallization.
      The latter process is described by a careful examination of the heterogeneous
      equilibria that govern the crystallization and its selectivity. Two variants of
      the preferential crystallization are detailed. A "good" example illustrates the
      productivity at the laboratory scale. The ratio between homochiral interaction
      energies and heterochiral interaction energies at different (hkl) interfaces are
      involved in the "difficult" cases where the entrainment effect is limited.

PMID- 19596101
TI  - Long-term stability of tramadol hydrochloride and droperidol mixture in 5%
      dextrose infusion polyolefin bags at 5+/-3 degrees C.
AB  - OBJECTIVE: To investigate the stability of tramadol hydrochloride 100mg
      associated with droperidol 2.5mg in 100ml of 5% dextrose solution stored at 5+/-3
      degrees C. METHODS: Solutions of 5% dextrose 100ml in polyolefin bags (n=5)
      containing approximately tramadol hydrochloride 100mg associated with droperidol
      2.5mg were prepared under aseptic conditions and stored about 32 days at 5+/-3
      degrees C. The tramadol hydrochloride and droperidol concentrations were measured
      by high performance liquid chromatography (HPLC). Visual inspection was performed
      and pH was measured periodically during the storage. Stability of the solutions
      was defined as the common regression line 95% lower confidence limit of the
      concentration remaining superior to 90% of the initial concentration as
      recommended by the Food and Drug Administration (FDA). RESULTS: No colour change
      or precipitation in the solutions was observed. Tramadol hydrochloride 100mg
      associated with droperidol 2.5mg in 100 ml of 5% dextrose infusions was stable
      when stored at 5+/-3 degrees C during 32 days. Throughout this period, the lower
      confidence limit of the estimated regression line of concentration-time profile
      remained above 90% of the initial concentration. There was no significant change
      in pH during storage. CONCLUSION: Under the conditions of this study, tramadol
      hydrochloride 100mg associated with droperidol 2.5mg in 100 ml of 5% dextrose
      infusions stored up to 32 days at 5+/-3 degrees C remain stable and may be
      prepared in advance by CIVAS to improve safety and management.

PMID- 19596102
TI  - [Antibiotic consumption in active French soldiers in 2007].
AB  - INTRODUCTION: Analysis of antibiotic consumption among active duty soldiers can
      contribute to the development of actions designed to avoid unsuitable population
      exposure to antibiotics. This survey was conducted among active soldiers to
      establish a reference year for refund data on antibiotic prescriptions by gender
      and age. Another aim was to use the refund data among soldiers to learn more
      about the pattern of antibiotic prescriptions by general practitioners. MATERIAL
      AND METHODS: A standardized dose of antibiotics prescribed by general
      practitioners in 2007 for the active duty military population in France was
      determined from an analysis of the Health fund database. The defined daily dose
      (DDD), as well as the DDD/1000 contributors to the national healthcare insurance
      fund, was then used as a technical unit of measurement. RESULTS: For the military
      population under study, the DDD was 15.76 per 1000 people. It was higher for
      women than for men (25.1 DDD for 1000 women vs 14.2 DDD for 1000 men). The DDD
      increased regularly with age: from 11.4 DDD for 1000 people aged less than 20 to
      19.3 DDD for 1000 people aged over 50. Military physicians accounted for only 4%
      of the prescribing practitioners. DISCUSSION: Careful analysis of antibiotic
      consumption together with closer cooperation between the military healthcare
      center and the National healthcare fund will enable the development of a
      prevention policy concerning health and better control of infectious risk.

PMID- 19596103
TI  - [Knowledge and perceptions of staff working in private dispensaries in Abidjan as
      regards bacterial resistance].
AB  - Private dispensaries play an important role in the use of drugs such as
      antibiotics at community level. However, the knowledge and perceptions of staff
      working in these private dispensaries as regards bacterial resistance have not
      been sufficiently studied. OBJECTIVES: To assess the knowledge and perceptions of
      staff working in private dispensaries in Abidjan as regards bacterial resistance.
      MATERIALS AND METHODS: A survey was carried out among 123 members of staff
      working in private dispensaries, during a horizontal study conducted in 18
      private dispensaries selected at random in the town of Abidjan in the Ivory
      Coast. Group meetings were also held to better understand the perceptions of
      staff working in these private dispensaries as regards bacterial resistance.
      RESULTS: Four antibiotics out of five bought in these private dispensaries in
      Abidjan were dispensed by pharmacy assistants. However, they were less informed
      than the pharmacists as regards bacterial resistance and the factors involved in
      its emergence. All the pharmacists interviewed in the study showed a good
      theoretical knowledge of bacterial resistance. However, the group meetings
      revealed that the risks of emergence of bacterial resistance in the case of
      antibiotics being dispensed without a prescription, and the threat of this
      resistance in terms of public health, were less perceived by the pharmacists.
      CONCLUSIONS: Assistants in dispensaries are less well-informed about bacterial
      resistance and the factors determining its emergence even though they dispense
      the most antibiotics to customers. Pharmacists have theoretical knowledge of
      bacterial resistance but are less conscious of its impact in terms of public
      health. Information campaigns on bacterial resistance are highly recommended as
      regards staff working in private dispensaries in Abidjan.

PMID- 19596104
TI  - [The salt content of food: a public health problem].
AB  - Salt abuse in nutrition may exert harmful effects on health, increasing arterial
      hypertension and its cardiovascular consequences. It is a risk factor,
      particularly for older subjects and those having chronic diseases such as
      arterial hypertension, some renal diseases, and obesity. In subjects more
      particularly vulnerable, the maintenance of sodium balance, which is mainly
      aldosterone dependent, is perturbed. Although the use of salt for food
      preservation has greatly declined, it remains a serious risk factor. Excessive
      salt intake however results more often from poor dietary habits. The WHO and
      AFSSA have advised to reduce daily salt intake to 5 g, whereas it is currently
      about 9-10 g. In spite of repeated warnings, salt abuse remains the causal agent
      for many disease conditions, mainly arterial hypertension. That is why
      legislative measures should be taken in order to limit the salt content of food
      industry products, particularly as a preservative in foods. A large-scale public
      information campaign would be necessary with participation of public health
      partners, particularly physicians and pharmacists.

PMID- 19596105
TI  - SIP Founders' Lecture and virus symposium, 2008.

PMID- 19596107
TI  - Focus on antibiotic stewardship. Introduction.

PMID- 19596108
TI  - MRSA burden and interventions.
AB  - Infections caused by meticillin-resistant Staphylococcus aureus (MRSA) remain a
      major problem worldwide. In England, the Department of Health set a target for
      decreasing MRSA bloodstream infections throughout the country by 50% by 2008,
      based on the 2003/2004 national figure. To aid hospitals in achieving their
      individual targets, guidance was provided in the form of care bundles, which were
      initially related to infection-control practices. Several studies have shown that
      decreasing the use of fluoroquinolones and/or cephalosporins results in a
      decrease in MRSA infection rates. In 2007 the Department of Health published
      guidance on antibiotic prescribing, following which the MRSA bloodstream
      infection rate dropped more rapidly than in 2006, and the target was met.

PMID- 19596109
TI  - Early antibiotic treatment failure.
AB  - There is no consensus on the definition of treatment failure. It is usually based
      on clinical signs, although microbiological and other biological markers may
      prove of value in the future. The major risk factors associated with treatment
      failure include an inadequate antimicrobial spectrum of the prescribed antibiotic
      and lack of, or insufficient, control of the source of the infection. In certain
      patient subpopulations additional specific factors may play a role. Reported
      treatment failure rates are unacceptably high, reaching up to 64%. Treatment
      failure is highly clinically relevant, as indicated by the associated constant
      finding of significantly increased length of hospital stay, higher mortality and
      greater healthcare costs. Proposed future initiatives include consensus
      statements on validated variables and definitions, both for general patient
      populations and specific subgroups. Investigation of the relative impact of
      modifiable risk factors may allow for the development of a treatment failure
      score for adequate stratification of individual cases. In patients in the high
      risk group, initial broad-spectrum antimicrobial coverage, and modifications to
      doses and the dosing schedule should be considered.

PMID- 19596110
TI  - Antibiotic resistance: the perfect storm.
AB  - The worldwide epidemic of antibiotic resistance is in danger of ending the golden
      age of antibiotic therapy. Resistance impacts on all areas of medicine, and is
      making successful empirical therapy much more difficult to achieve. Antibiotic
      choices are often severely restricted, and the pipeline of new antibiotics is
      almost dry. Resistance cannot be prevented, but its development and spread can be
      slowed. One of the tools at our disposal is maximising diversity in our
      prescribing. The advent of tigecycline, the first in a new class of intravenous
      antibiotics, is important in this context, giving us a further monotherapy option
      for severe infections. Another strategy is seriously to curtail the large amount
      of unnecessary antibiotic use in many areas of life, not only medical practice.
      The various aspects of this strategy are briefly reviewed.

PMID- 19596111
TI  - The tide of antimicrobial resistance and selection.
AB  - The cumulative ecological damage, both to the individual patient and to patient
      populations, secondary to antibiotic prescribing is increasingly recognised. The
      impact of antibiotics on pathogens and normal flora should be a criterion for
      antimicrobial selection. Measures to reduce the use of third-generation
      cephalosporins and fluoroquinolones should be considered. Increased reliance on
      carbapenems may accelerate the emergence of extremely resistant isolates, and
      these antimicrobials should be restricted to key scenarios. There is a clear need
      for new agents with novel modes of action and low ecological damage potential to
      treat nosocomial infections. Tigecycline has a spectrum of activity that
      theoretically may reduce the selection pressure for key nosocomial pathogens, and
      represents an alternative to carbapenems. Further studies are needed to confirm
      this potentially low selection pressure.

PMID- 19596112
TI  - Non-arteritic anterior ischaemic optic neuropathy: a review and update.
AB  - Non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common
      acute optic neuropathy in people aged 50 years and older. The condition is caused
      by infarction of the laminar or retrolaminar portion of the optic nerve head
      supplied by the short posterior ciliary arteries (SPCAs). The underlying
      aetiology and pathophysiology is poorly elucidated. Factors that have been
      implicated include nocturnal hypotension, impaired autoregulation of the
      microvascular supply, vasculopathic occlusion, and venous insufficiency. These
      factors are thought to result in axonal oedema causing a compartment syndrome in
      a structurally crowded optic disc leading to axonal degeneration and loss of
      retinal ganglion cells via apoptosis. Clinically NAION is characterised by
      sudden, usually painless, loss of vision in one or both eyes. Examination
      findings include decreased visual acuity, a visual field defect, decreased colour
      vision, a relative afferent pupillary defect, and optic disc swelling. Despite
      significant research, treatment options for NAION remain limited.

PMID- 19596115
TI  - Editorial. Comments and criticisms.

PMID- 19596114
TI  - Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid
      after subarachnoid hemorrhage: a possible role as a spasmogen.
AB  - This study investigates the role of sphingosylphosphorylcholine (SPC) in the
      mechanisms underlying cerebral vasospasm after subarachnoid hemorrhage (SAH). The
      levels of SPC were measured in cerebrospinal fluid (CSF) of patients with SAH and
      also in an experimental canine model. CSF samples were collected from 11 patients
      with SAH, and from dogs that had received an injection of SPC into the cisterna
      magna to examine SPC kinetics in the CSF. SPC was assayed using solid-phase
      extraction and triple quadrupole mass spectrometry. The SPC concentrations in SAH
      patients on days 3, 8, and 14 after the onset of SAH were significantly higher
      than those in normal CSF. In the canine model, rapid dilution of SPC in CSF was
      observed. In combination with data from previous studies, these results suggest
      that SPC is involved in the development of cerebral vasospasm. Rapid dilution of
      SPC in CSF suggests that SPC is released into CSF at higher concentrations than
      those measured in the present study.

PMID- 19596113
TI  - Deep brain stimulation for Parkinson's disease: Australian referral guidelines.
AB  - The advent of deep brain stimulation (DBS) has been an important advance in the
      treatment of Parkinson's disease (PD). DBS may be employed in the management of
      medication-refractory tremor or treatment-related motor complications, and may
      benefit between 4.5% and 20% of patients at some stage of their disease course.
      In Australia, patients with PD are reviewed by specialised DBS teams who assess
      the likely benefits and risks associated with DBS for each individual. The aim of
      these guidelines is to assist neurologists and general physicians identify
      patients who may benefit from referral to a DBS team. Common indications for
      referral are motor fluctuations and/or dyskinesias that are not adequately
      controlled with optimised medical therapy, medication-refractory tremor, and
      intolerance to medical therapy. Early referral for consideration of DBS is
      recommended as soon as optimised medical therapy fails to offer satisfactory
      motor control.

PMID- 19596116
TI  - Giant condyloma with demise secondary to meningococcemia in an infant boy.
AB  - Human papilloma virus (HPV) is the most common sexually transmitted disease among
      adults in the USA; however, the presence of HPV in infants is rare. Condyloma
      acuminata, a cutaneous, fungating lesion caused by HPV, has a generally mild
      course that often resolves spontaneously or can be managed both medically and
      surgically. Typical treatments for condyloma include imiquimoid cream, podofilox
      gel, podophyllin resin, cryotherapy, laser surgery, tangential shave excision,
      and electrocautery. Rapidly progressing condyloma acuminata followed by a fatal
      course of Neisseria meningitis in an infant is an extremely rare presentation
      that merits further investigation into possible immunologic etiology. A 7-month
      old circumcised Caucasian boy presented with a rapidly progressing giant penile
      condyloma acuminatum. This is the youngest documented case of this type.
      Refractory to medical and surgical treatments, this otherwise apparently healthy
      child was referred to pediatric immunology. Normal complete blood count led to
      deferment, suggesting further medical and surgical treatment. Five days after
      such treatment, the baby presented with progressive systemic rash, fever and
      tachycardia. The patient died from meningococcemia. This case serves as a warning
      concerning the course of condyloma in infants. Immunologic investigation may be
      critically important in young patients refractory to designated treatments for
      condyloma.

PMID- 19596118
TI  - Preliminary clinical experiences of a motorized manipulator for magnetic
      resonance image-guided microwave coagulation therapy of liver tumors.
AB  - BACKGROUND: In magnetic resonance (MR) image-guided microwave thermocoagulation
      of liver tumors, the choice of the optimal puncture route is an important and
      time-consuming process. To assist this process, we have developed a motorized MR
      compatible manipulator. METHODS: The manipulator consists of a passive end
      effecter with 2 degrees-of-freedom (DOF) rotation and active base stages with 3
      ultrasonic motors. It automatically chases the preset target point with
      synergetic remote-center-of-motion (RCM) control. A mechanical torque limiter and
      an electrical shutdown switch were added for patient safety. RESULTS: The
      manipulator was used for this procedure in 15 cases and successfully utilized to
      treat liver tumors in various locations. Thoracoscopic assistance was combined
      with the manipulator in 6 cases. No complications were experienced. CONCLUSIONS:
      The manipulator was found to be very effective for assisting MR-guided microwave
      coagulation of liver tumors.

PMID- 19596117
TI  - Long-term follow-up results of breast cancer patients with sentinel lymph node
      biopsy using periareolar injection.
AB  - BACKGROUND: Areolar injection for sentinel lymph node biopsy (SLNB) in breast
      cancer surgery has been adopted by many institutions. However, only one study has
      reported the follow-up results for patients whose SLNB was performed with this
      injection method alone. METHODS: Three hundred eighty patients with breast cancer
      underwent SLNB with periareolar injection of both blue dye and radiotracer. The
      follow-up consisted of a physical examination every 3 months and annual
      mammography. RESULTS: Of 380 patients with SLNB, 261 were found to have negative
      sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39
      months (range 13-74), 2 of the 261 patients developed axillary recurrence for an
      axillary relapse incidence of .77%. Five-year distant disease-free survival was
      96.9%, and overall survival was 99.4%. CONCLUSIONS: The incidence of axillary
      recurrence for the areolar injection method was low and consistent with that
      reported in other observational studies using other injection methods.

PMID- 19596119
TI  - The ratio between metastatic and examined lymph nodes is an independent
      prognostic factor for patients with resectable middle and distal bile duct
      carcinoma.
AB  - BACKGROUND: The lymph node ratio, defined as the ratio between the number of
      lymph node metastasis and the total number of lymph nodes examined, has been
      reported to be an important prognostic factor in other gastrointestinal
      carcinomas except middle and distal bile duct carcinomas. METHODS: Between 1991
      and 2004, 62 consecutive patients who underwent surgery for middle and distal
      bile duct carcinoma were retrospectively analyzed concerning prognostic factors.
      RESULTS: The median number of lymph nodes examined was 12 (range 5 to 38). The
      overall 5-year survival rates of patients with lymph node ratio of 0, lymph node
      ratio of 0 to .2, and lymph node ratio >.2 were 62%, 41%, and 0%, respectively. A
      multivariate analysis revealed that a lymph node ratio >.2 and perineural
      invasion were independent predictive factors for survival. CONCLUSIONS: Lymph
      node ratio >.2 is an important factor to predict survival after resected middle
      and distal bile duct carcinoma.

PMID- 19596120
TI  - Prenatal smoking might not cause attention-deficit/hyperactivity disorder:
      evidence from a novel design.
AB  - BACKGROUND: It is widely considered that exposure to maternal cigarette smoking
      in pregnancy has risk effects on offspring attention-deficit/hyperactivity
      disorder (ADHD). This view is supported by consistent observations of
      association. It is, however, impossible to be certain of adequate control for
      confounding factors with observational designs. We use a novel "natural
      experiment" design that separates prenatal environmental from alternative
      inherited effects. METHODS: The design is based on offspring conceived with
      Assisted Reproductive Technologies recruited from 20 fertility clinics in the
      United Kingdom and United States who were: 1) genetically unrelated, and 2)
      related to the woman who underwent the pregnancy. If maternal smoking in
      pregnancy has true risk effects, association will be observed with ADHD
      regardless of whether mother and offspring are related or unrelated. Data were
      obtained from 815 families of children ages 4 years-11 years with parent
      questionnaires and antenatal records. Birth weight was used as a comparison
      outcome. The key outcome considered was child ADHD symptoms. RESULTS: Association
      between smoking in pregnancy and lower birth weight was found in unrelated and
      related mother-offspring pairs, consistent with a true risk effect. However, for
      ADHD symptoms, the magnitude of association was significantly higher in the
      related pairs (beta = .102, p < .02) than in the unrelated pairs (beta= -.052, p
      > .10), suggesting inherited effects. CONCLUSIONS: Our findings highlight the
      need to test causal hypotheses with genetically sensitive designs. Inherited
      confounds are not necessarily removed by statistical controls. The previously
      observed association between maternal smoking in pregnancy and ADHD might
      represent an inherited effect.

PMID- 19596121
TI  - Interaction of childhood maltreatment with the corticotropin-releasing hormone
      receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity.
AB  - BACKGROUND: Variation in the corticotropin-releasing hormone receptor (CRHR1)
      gene has been shown to interact with early life stress to predict adult
      depression. This study was conducted to determine whether CRHR1 polymorphisms
      interact with childhood maltreatment to predict hypothalamic-pituitary-adrenal
      (HPA) axis reactivity, which has been linked to both depression and early life
      stress. METHODS: One hundred twenty-nine White, non-Hispanic adults completed the
      Childhood Trauma Questionnaire and the dexamethasone/corticotropin-releasing
      hormone (DEX/CRH) test, and provided blood samples for genotyping of two CRHR1
      polymorphisms. RESULTS: Both rs110402 and rs242924 (which were in tight linkage
      disequilibrium, D' = .98) showed a significant interaction with maltreatment in
      the prediction of cortisol response to the DEX/CRH test (p < .05). For subjects
      with maltreatment, the GG genotype of each single nucleotide polymorphism was
      associated with elevated cortisol responses to the test. CONCLUSIONS: Variation
      in the CRHR1 moderates the effect of childhood maltreatment on cortisol responses
      to the DEX/CRH test. Excessive HPA axis activation could represent a mechanism of
      interactions of risk genes with stress in the development of mood and anxiety
      disorders.

PMID- 19596122
TI  - The involvement of retinoic acid receptor-alpha in corticotropin-releasing
      hormone gene expression and affective disorders.
AB  - BACKGROUND: Corticotropin-releasing hormone (CRH) is considered the central
      driving force in the stress response and plays a key role in the pathogenesis of
      depression. Retinoic acid (RA) has been suggested by clinical studies to be
      associated with affective disorders. METHODS: First, hypothalamic tissues of 12
      patients with affective disorders and 12 matched control subjects were studied by
      double-label immunofluorescence to analyze the expression of CRH and retinoic
      acid receptor-alpha (RAR-alpha). Second, critical genes involved in the RA
      signaling pathways were analyzed in a rat model of depression. Finally, the
      regulatory effect of RAR-alpha on CRH gene expression was studied in vitro.
      RESULTS: We found that the expression of RAR-alpha was colocalized with CRH
      neurons in human hypothalamic paraventricular nucleus (PVN). The density of RAR
      alpha-immunoreactive neurons and CRH-RAR-alpha double-staining neurons was
      significantly increased in the PVN of patients with affective disorders. The
      ratio of the CRH-RAR-alpha double-staining neurons to the CRH-immunoreactive
      neurons in affective disorder patients was also increased. Recruitment of RAR
      alpha by the CRH promoter was observed in the rat hypothalamus. A dysregulated RA
      metabolism and signaling was also found in the hypothalamus of a rat model for
      depression. Finally, in vitro studies demonstrated that RAR-alpha mediated an
      upregulation of CRH gene expression. CONCLUSIONS: These results suggest that RAR
      alpha might contribute to regulating the activity of CRH neurons in vivo, and the
      vulnerable character of the critical proteins in RA signaling pathways might
      provide novel targets for therapeutic strategies for depression.

PMID- 19596123
TI  - From specificity to sensitivity: how acute stress affects amygdala processing of
      biologically salient stimuli.
AB  - BACKGROUND: A vital component of an organism's response to acute stress is a
      surge in vigilance that serves to optimize the detection and assessment of
      threats to its homeostasis. The amygdala is thought to regulate this process, but
      in humans, acute stress and amygdala function have up to now only been studied in
      isolation. Hence, we developed an integrated design using functional magnetic
      resonance imaging to investigate the immediate effects of controlled stress
      induction on amygdala function. METHODS: In 27 healthy female participants, we
      studied brain responses to emotional facial stimuli, embedded in an either
      acutely stressful or neutral context by means of adjoining movie clips. RESULTS:
      A variety of physiological and psychological measures confirmed successful
      induction of moderate levels of acute stress. More importantly, this context
      manipulation shifted the amygdala toward higher sensitivity as well as lower
      specificity, that is, stress induction augmented amygdala responses to equally
      high levels for threat-related and positively valenced stimuli, thereby
      diminishing a threat-selective response pattern. Additionally, stress amplified
      sensory processing in early visual regions and the face responsive area of the
      fusiform gyrus but not in a frontal region involved in task execution.
      CONCLUSIONS: A shift of amygdala function toward heightened sensitivity with
      lower levels of specificity suggests a state of indiscriminate hypervigilance
      under stress. Although this represents initial survival value in adverse
      situations where the risk for false negatives in the detection of potential
      threats should be minimized, it might similarly play a causative role in the
      sequelae of traumatic events.

PMID- 19596124
TI  - Synthesis and characterization of Fe2O3/SiO2 nanocomposites.
AB  - Fe2O3/SiO2 nanocomposites based on fumed silica A-300 (S(BET)=337 m2/g) with iron
      oxide deposits at different content were synthesized using Fe(III)
      acetylacetonate (Fe(acac)3) dissolved in isopropyl alcohol or carbon
      tetrachloride for impregnation of the nanosilica powder at different amounts of
      Fe(acac)3 then oxidized in air at 400-900 degrees C. Samples with Fe(acac)3
      adsorbed onto nanosilica and samples with Fe2O3/SiO2 including 6-17 wt% of Fe2O3
      were investigated using XRD, XPS, TG/DTA, TPD MS, FTIR, AFM, nitrogen adsorption,
      Mossbauer spectroscopy, and quantum chemistry methods. The structural
      characteristics and phase composition of Fe2O3 deposits depend on reaction
      conditions, solvent type, content of grafted iron oxide, and post-reaction
      treatments. The iron oxide deposits on A-300 (impregnated by the Fe(acac)3
      solution in isopropanol) treated at 500-600 degrees C include several phases
      characterized by different nanoparticle size distributions; however, in the case
      of impregnation of A-300 by the Fe(acac)3 solution in carbon tetrachloride only
      alpha-Fe2O3 phase is formed in addition to amorphous Fe2O3. The Fe2O3/SiO2
      materials remain loose (similar to the A-300 matrix) at the bulk density of 0.12
      0.15 g/cm3 and S(BET)=265-310 m2/g.

PMID- 19596125
TI  - Temperature and salt-induced micellization of dodecyltrimethylammonium chloride
      in aqueous solution: a thermodynamic study.
AB  - Thermodynamics of micelle formation of the cationic surfactant
      dodecyltrimethylammonium chloride (DTAC) in water and aqueous NaCl solutions were
      investigated. Isothermal titration calorimetry (ITC) has been used to study the
      effect of the added NaCl on the critical micelle concentration, cmc, and enthalpy
      of micellization, Delta(mic)H(o), between 278.15 and 318.15K. Gibbs free energy,
      Delta(mic)G(o), and entropy, Delta(mic)S(o), were deduced by taking into account
      the counterion binding. From the temperature dependence of Delta(mic)H(o) the
      heat capacities of micellization, Delta(mic)c(p)(o), were determined. NaCl shifts
      cmc strongly towards lower values, indicating the screening of the repulsions of
      the polar head groups by counterions; but it influences Delta(mic)H(o) at higher
      concentrations of salt only. Delta(mic)G(o) is always negative and slightly
      temperature dependent. The temperature dependence of Delta(mic)S(o) indicates
      that the process of micellization is entropically driven. Delta(mic)H(o)
      decreases strongly with increasing temperature and passes through zero
      (endothermic to exothermic processes). The temperature dependence of the critical
      micelle concentration exhibits a minimum characterized by Delta(mic)H(o)=0, where
      Delta(mic)G(o) is of purely entropic contribution in all solutions.
      Delta(mic)c(p)(o) are strongly negative in all solvents, relating directly to the
      removal of water accessible non-polar surface of DTAC in the presence of excess
      counterions also.

PMID- 19596126
TI  - Hydrogen-bonding A(LS)2-type low-molecular-mass gelator and its thermotropic
      mesomorphic behavior.
AB  - A unique cholesterol-based A(LS)2-type gelator, which is a hydrogen-bonding
      complex based on an ALS-type non-gelator molecule 3-cholesteryl 4-(trans-2-(4
      pyridinyl)vinyl)phenyl succinate and a counterpart 3
      cholesteryloxycarbonylpropanoic acid, shows strong gelation ability in alcohol
      and aromatic solvents. The formed gel has a high Tg at low gelation
      concentration, and its xerogel shows fibrillar microstructure revealed by
      scanning electron microscopy (SEM). FTIR confirms the existence of intermolecular
      hydrogen bond in the gelator, and X-ray diffraction (XRD) analysis reveals that
      the gelator possesses a folded conformation in gel and self-assembles into the
      fibrillar structure mainly by van der Waals interaction between cholesteryl
      moieties of the gelator. Further more, the thermotropic behavior of the xerogel
      is studied by differential scanning calorimetry (DSC) and polarized optical
      microscopy (POM), which shows typical optical textures of liquid crystals.

PMID- 19596127
TI  - Gender effects in relapsing-remitting multiple sclerosis: correlation between
      clinical variables and gene expression molecular pathways.
AB  - Gene expression profiles were assessed in patients with relapsing-remitting
      multiple sclerosis (RRMS) to identify gender effects. Clear gender differences in
      time to second relapse and time to EDSS=6.0 progression in patients with late
      onset of the disease (>40years) were evident, and occurred more rapidly in female
      RRMS patients. Identified molecular biological mechanisms were related to
      increased immune activation associated with prominent inhibition of apoptosis
      that enhanced inflammatory processes and were more evident in female RRMS
      patients. Our findings open possibilities to explore gender-dependent
      immunomodulatory treatments that will be based on gene expression mechanisms that
      set the difference between male and female RRMS patients.

PMID- 19596129
TI  - The inoculum effect on the ammonia-oxidizing bacterial communities in parallel
      sequential batch reactors.
AB  - Three identical sequential batch reactors (SBRs) were each inoculated with sludge
      from a full-scale wastewater treatment plant (WWTP) treating a waste stream of
      different origin, i.e. a hospital, a meat processing company, and a municipal
      WWTP. The SBRs were run in parallel for 84 consecutive days to investigate
      whether the reactors would become more phylogenetically similar or stay separated
      concerning their functionality and microbial communities. Overall, the
      nitrification functionality was high throughout the experiment, and the size and
      structure of the sludge flocs were very similar. The total bacterial and ammonia
      oxidizing bacterial (AOB) communities were analyzed by PCR-DGGE. Cluster analysis
      demonstrated very distinct bacterial communities in the three SBRs, not showing
      any trend becoming more similar. The carrying capacity, dynamics and functional
      organization of the communities were assessed by DGGE analysis and based on these
      patterns the range-weighted richness, moving window analysis, and constructing
      Pareto-Lorenz evenness distribution curves were calculated. Between the SBRs,
      highly comparable internal structure and dynamics of the AOB communities were
      observed, although they had only one AOB DGGE band in common. These observations
      indicate that community characteristics such as the extent of biodiversity and
      dynamics are more important indicators of good microbial functionality than the
      presence of certain specific species.

PMID- 19596130
TI  - Identification of biofoulant of membrane bioreactors in soluble microbial
      products.
AB  - To reveal primary biofoulant in soluble microbial products (SMP) and/or soluble
      extracellular polymeric substances (EPS), after removal of sludge particles,
      activated sludge samples were subjected to microfiltration tests in a submerged
      MBR. Filtration resistance directly correlates with the saccharide concentration.
      Saccharides in wastewater from several sources contained uronic acids, which
      increased the filtration resistance. When the microfiltration test liquids
      contained saccharides over 80mg l(-1), a gelatinous mass remained on the membrane
      surface after filtration and contained concentrations of saccharides and uronic
      acids 50 times higher than the original test liquid while only trace amounts of
      these substances were contained in the filtrate. The gelatinous mass contained
      high molecular weight substances of 10(6)-10(8)Da, suggesting the presence of
      polysaccharides. However, molecules of this size were calculated to be much
      smaller than the pore size of the membrane. Ethylenediaminetetraacetic acid
      decreased filtration resistance, suggesting that polysaccharides containing
      uronic acid units could undergo intermolecular or intramolecular ionic cross
      linking by polyvalent cations and form the gel, thus clogging the membrane pores
      as an actual biofoulant.

PMID- 19596128
TI  - Prevaccination genomic diversity of human papillomavirus genotype 6 (HPV 6).
AB  - Prevaccination genomic diversity of human papillomavirus genotype 6 (HPV 6) was
      established by sequencing 3798 bp of 77 clinically important HPV 6 isolates
      obtained from 45 and 32 patients with genital warts and laryngeal papillomas,
      respectively. By analyzing pooled L1, LCR, E6, E2, and E5 nucleotide data of an
      individual isolate, a total of 36 different genomic variants were identified, of
      which six (12 isolates), one (one isolate) and 29 (64 isolates) corresponded to
      HPV 6b, HPV 6a, and HPV 6vc genetic lineages, respectively. Several novel,
      potentially important mutations were identified. Non-prototypic HPV 6vc genomic
      variants were found in the majority of genital warts and laryngeal papillomas
      included in the study. The presence of serious HPV 6 genome sequence errors was
      confirmed and novel sequence errors were identified in sequence repositories.

PMID- 19596132
TI  - Seasonal dynamics of biodegradation activities for dimethylarsinic acid (DMA) in
      Lake Kahokugata.
AB  - The microbial activities in aquatic environments significantly influence arsenic
      cycles such as the turnover between inorganic arsenic and organoarsenic
      compounds. In Lake Kahokugata, inorganic arsenic was detected at concentrations
      ranging from 2.8 to 23nM in all seasons, while the concentrations of
      dimethylarsinic acid (DMA) produced by microorganisms such as phytoplankton
      changed seasonally and showed a peak in winter. The changes in the concentrations
      of methylarsenic species did not correlate with the changes in phytoplankton
      abundance (chlorophyll a contents), suggesting that DMA-degradation is related to
      this inconsistency. DMA (1microM) added into the lake water was converted to
      inorganic arsenic at 20 degrees C only under anaerobic and dark conditions, while
      DMA degradation was diminished under aerobic or light conditions. Moreover, DMA
      added to the lake water samples collected through four seasons was degraded at
      the same rates under anaerobic and dark conditions at 20 degrees C. However, at
      30 degrees C, 1microM of DMA in the summer lake water samples was rapidly
      degraded in 7 and 21d. In contrast, DMA degradation was diminished in the winter
      lake water samples at 4 degrees C of incubation. Presumably, DMA-biodegradation
      activities are mainly controlled by changes in the water temperature in Lake
      Kahokugata, where the arsenic concentrations change seasonally.

PMID- 19596131
TI  - Heterogenous photocatalytic degradation kinetics and detoxification of an urban
      wastewater treatment plant effluent contaminated with pharmaceuticals.
AB  - Degradation kinetics and mineralization of an urban wastewater treatment plant
      effluent contaminated with a mixture of pharmaceutical compounds composed of
      amoxicillin (10 mg L(-1)), carbamazepine (5 mg L(-1)) and diclofenac (2.5 mg L(
      1)) by TiO(2) photocatalysis were investigated. The photocatalytic effect was
      investigated using both spiked distilled water and actual wastewater solutions.
      The process efficiency was evaluated through UV absorbance and TOC measurements.
      A set of bioassays (Daphnia magna, Pseudokirchneriella subcapitata and Lepidium
      sativum) was performed to evaluate the potential toxicity of the oxidation
      intermediates. A pseudo-first order kinetic model was found to fit well the
      experimental data. The mineralization rate (TOC) of the wastewater contaminated
      with the pharmaceuticals was found to be really slow (t(1/2)=86.6 min) compared
      to that of the same pharmaceuticals spiked in distilled water (t(1/2)=46.5 min).
      The results from the toxicity tests of single pharmaceuticals, their mixture and
      the wastewater matrix spiked with the pharmaceuticals displayed a general
      accordance between the responses of the freshwater aquatic species (P.
      subscapitata>D. magna). In general the photocatalytic treatment did not
      completely reduce the toxicity under the investigated conditions (maximum
      catalyst loading and irradiation time 0.8 g TiO(2) L(-1) and 120 min
      respectively).

PMID- 19596134
TI  - Laboratory investigation of reducing two algae from eutrophic water treated with
      light-shading plus aeration.
AB  - The occurrence of harmful algal bloom in water source poses a serious water
      safety problem to local water supply systems. In order to ensure the raw water
      quality, the feasibility of reducing harmful algae by light-shading plus aeration
      was investigated. The batch test showed that algal biomass reduced rapidly under
      light-shading condition, and the reduction efficiency was further increased when
      light-shading was accompanied by aeration. The continuous flow experiment showed
      that the algal reduction efficiency increased with the increase of residence
      time. At residence time of 5 d, when treated with light-shading plus aeration,
      algal biomass could be reduced by more than 65%, with raw water quality improved
      simultaneously. Furthermore, considering that some harmful algae such as
      Microcystis tend to float upwards under light-limited condition, an integrated
      light-shading system consisting of pre-separation process and light-shading plus
      aeration treatment was suggested to treat naturally high algal water. The result
      showed that pre-separation process could remove more than 40% of algal biomass,
      and the total reduction efficiency of the integrated system increased to above
      80%.

PMID- 19596133
TI  - Nonylphenol ethoxylates and their metabolites in sewage treatment plants and
      rivers of Tianjin, China.
AB  - Nonylphenol polyethoxylates (NPnEO) and nonylphenol (NP) have provoked much
      environmental concern because of their weak estrogenic activities. We monitored
      NPnEO and their metabolites in rivers in Tianjin and in a sewage treatment plant
      of Tianjin monthly for 1 year. The total concentrations of NPnEO and NP in
      influent, up to 47.2 microgL(-1) in August, were higher in summer than in other
      seasons. During the 12 months survey, NP was accumulated in most effluent samples
      with a mean value of 2.92 microgL(-1). The average concentrations of nonylphenol
      monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO) and nonylphenol
      triethoxylate (NP3EO) in effluents were 1.26, 1.53 and 1.06 microgL(-1), which
      corresponds to percent removals of 75%, 60% and 62%, respectively. In rivers of
      Tianjin, NP2EO and nonylphenoxyethoxy acetic acid (NP2EC) exhibited the highest
      concentrations in the surface water, up to 1.38 and 9.59 microgL(-1),
      respectively. The pollution of nonylphenolic substances in sediments of Haihe
      River belongs to moderate or severe level in the world, with the total
      concentration between 4.1 and 9.9 microgg(-1), dry weight.

PMID- 19596135
TI  - Degradation of pentachlorobiphenyl by a sequential treatment using Pd coated iron
      and an aerobic bacterium (H1).
AB  - The reductive dechlorination and biodegradation of 2,2(')4,5,5(')
      pentachlorobiphenyl (PCB#101) was investigated in a laboratory-scale. Palladium
      coated iron (Pd/Fe) was used as a catalytic reductant for the chemical
      degradation of 2,2(')4,5,5(')-pentachlorobiphenyl, and an aerobic bacteria was
      used for biodegradation following the chemical reaction in this study.
      Dechlorination was affected by several factors such as Pd loading, initial soil
      pH and the amount of Pd/Fe used. The results showed that higher Pd loading,
      higher dosage of Pd/Fe and slightly acid condition were beneficial to the
      catalytic dechlorination of 2,2('),4,5,5(')-pentachlorobiphenyl. In laboratory
      batch experiments, 2,2(')4,5,5(')-pentachlorobiphenyl was reduced in the presence
      of Pd/Fe bimetal, which was not further degraded by aerobic bacteria. 2,2('),4
      trichlorobiphenyl (PCB#17), a reduction product from 2,2(')4,5,5(')
      pentachlorobiphenyl, was readily biodegraded in the presence of a aerobic
      bacterial strain. It is suggested that an integrated Pd/Fe catalytic reduction
      aerobic biodegradation process may be a feasible option for treating PCB
      contaminated soil.

PMID- 19596136
TI  - Complete biodegradation of atrazine by a microbial community isolated from a
      naturally derived river ecosystem (microcosm).
AB  - A microbial community, designated as AN4, capable of mineralizing the herbicide
      atrazine was isolated from a model river ecosystem (microcosm). The profile of
      degradation of atrazine by the AN4 community seemed to well reflect what occurred
      in the microcosm: rapid degradation of atrazine and transient accumulation of
      cyanuric acid, followed by relatively slow mineralization. The community
      comprised multiple phylogenetically distinct microbial strains, and the microbes
      were suspended and probably aggregated in the water phase of the microcosm.
      Denaturing gradient gel electrophoresis (DGGE) revealed that multiple bacterial
      strains exist in the AN4 community, and we successfully isolated two strains,
      which belonged to the genera Nocardioides and Pedomicrobium. Nocardioides sp.
      strain AN4-4 degraded atrazine to cyanuric acid and harbored the trzN and atzC
      genes encoding the s-triazine-degrading enzymes. This strain also degraded other
      chloro-substituted s-triazines like simazine and propazine, but it showed little
      degradability for simetryn (a methylthio-substituted s-triazine). Additionally,
      strain AN4-4 could grow on basal salt agar containing ethylamine or
      isopropylamine as the only carbon and nitrogen sources. Another strain,
      Pedomicrobium sp. strain AN4-9 could mineralize cyanuric acid alone. Therefore,
      we found that the coexistence of these two community members functionally serves
      to completely biodegrade atrazine.

PMID- 19596137
TI  - Selenium and trace element mobility affected by periodic displacement of
      stratification in the Great Salt Lake, Utah.
AB  - The Great Salt Lake (GSL) is a unique ecosystem in which trace element activity
      cannot be characterized by standard geochemical parameters due to the high
      salinity. Movement of selenium and other trace elements present in the lake bed
      sediments of GSL may occur due to periodic stratification displacement events or
      lake bed exposure. The water column of GSL is complicated by the presence of a
      chemocline persistent over annual to decadal time scales. The water below the
      chemocline is referred to as the deep brine layer (DBL), has a high salinity
      (16.5 to 22.9%) and is anoxic. The upper brine layer (UBL) resides above the
      chemocline, has lower salinity (12.6 to 14.7%) and is oxic. Displacement of the
      DBL may involve trace element movement within the water column due to changes in
      redox potential. Evidence of stratification displacement in the water column has
      been observed at two fixed stations on the lake by monitoring vertical water
      temperature profiles with horizontal and vertical velocity profiles.
      Stratification displacement events occur over periods of 12 to 24h and are
      associated with strong wind events that can produce seiches within the water
      column. In addition to displacement events, the DBL shrinks and expands in
      response to changes in the lake surface area over a period of months. Laboratory
      tests simulating the observed sediment re-suspension were conducted over daily,
      weekly and monthly time scales to understand the effect of placing anoxic bottom
      sediments in contact with oxic water, and the associated effect of trace element
      desorption and (or) dissolution. Results from the laboratory simulations indicate
      that a small percentage (1%) of selenium associated with anoxic bottom sediments
      is periodically solubilized into the UBL where it potentially can be incorporated
      into the biota utilizing the oxic part of GSL.

PMID- 19596138
TI  - The antiphospholipid syndrome as a neurological disease.
AB  - OBJECTIVES: To examine currently known and additional potential neurological
      manifestations of the antiphospholipid syndrome (APS) and to discuss current and
      experimental therapeutic options in light of the present knowledge of the disease
      mechanism. METHODS: The PubMed database was searched for articles published
      between the years 1980 and 2008 for keywords referring to APS and several
      neurological conditions. Relevant English language articles were reviewed.
      RESULTS: APS is characterized by diverse neurological manifestations. These
      include cerebral ischemic events, epilepsy, dementia, cognitive deficits,
      headaches, psychiatric disorders, chorea, multiple sclerosis-like, transverse
      myelitis, and ocular symptoms. Some of the symptoms can be associated with
      ischemia; however, other mechanisms that could lead to similar outcomes have been
      described, such as direct binding of antiphospholipid antibodies to neural
      tissue. Current treatment guidelines concern cerebrovascular events only. We
      propose several different therapeutic options related to the autoimmune nature of
      the syndrome. CONCLUSION: Neurological manifestations in APS are diverse and may
      be confused with other neurologic syndromes. This information is important for
      the proper diagnosis and management of patients. Experimental therapeutic
      alternatives expand the treatment options for patients and physicians.

PMID- 19596139
TI  - A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage
      III optimally debulked ovarian cancer treated with intraperitoneal compared to
      intravenous chemotherapy: an analysis of patients enrolled in GOG 172.
AB  - OBJECTIVE: Serum CA-125 values have been advocated in the monitoring of ovarian
      cancer patients receiving intravenous (IV) chemotherapy. This evaluation sought
      to determine if the CA-125 test can be used to monitor treatment effect among
      patients receiving intraperitoneal chemotherapy (IP). METHODS: Patient charts
      from a phase III clinical trial (GOG 172) were retrospectively reviewed. Serum CA
      125 levels prior to each cycle of therapy were collected and compared between the
      IV and IP chemotherapy delivery. The association between CA-125 and progression
      free survival (PFS) or overall survival (OS) was estimated and the homogeneity of
      the results between IP and IV chemotherapy was assessed. RESULTS: A total of 177
      patients were treated with IV chemotherapy and 165 patients with IP chemotherapy
      with CA-125 data available were included in this analysis. The observed
      difference was not statistically significant in median CA-125 levels between the
      IV and IP arms at any time point (P>0.05 for all). Following surgery and adjuvant
      chemotherapy, patients with an abnormal CA-125 >35 U/ml were 2.45 times more
      likely to have disease progression (95% CI: 1.52-3.95, P<0.001) and 2.78 times
      more likely to die of disease (95% CI: 1.66-4.65, P<0.001), compared to those
      with a CA-125 <35 U/ml. These results were consistent with IP and IV
      chemotherapy. CONCLUSION: Serum CA-125 levels decrease in a similar manner during
      IP chemotherapy when compared to IV chemotherapy. Serum CA-125 algorithms for
      monitoring treatment effect that have been established for IV chemotherapy may
      also be applied for patients receiving IP chemotherapy.

PMID- 19596140
TI  - p16INK4A in routine practice as a marker of cervical epithelial neoplasia.
AB  - OBJECTIVE: The aim of this study was to validate the role of p16(INK4a)
      immunocytochemistry as a marker of cervical epithelial neoplasia in cytology and
      biopsy samples. METHODS: During the period of 4 years a total of 501
      immunocytochemistry stains in cytology and biopsy samples were performed. The
      cytology smears were obtained from two independent laboratories of women with low
      grade squamous intraepithelial lesion interpretation of Pap test or ThinPrep.
      Additionally, a selection of paraffin blocks from cases diagnosed previously with
      squamous intraepithelial lesion and cervical cancer were immunostained. RESULTS:
      Among 312 cytology samples analyzed by immunocytochemistry, 36.2% were positive
      for p16(INK4a). Negative cases were followed-up with conventional Pap smear and
      86.9% showed regression. Among positive patients, 14 underwent surgery and 100%
      exhibited squamous intraepithelial lesion. In additional immunohistochemical
      analysis of selected biopsies from our archive, we found that the ratio of
      positivity for p16(INK4a) increased from 40% in L-SIL/CIN1 to 69.8% in H-SIL/CIN2
      to 100% in H-SIL/CIN3 and squamous cell carcinoma. A relatively low number (24%)
      of cases with squamous metaplasia revealed focal and/or sporadic staining in the
      superficial layers of the epithelium. All the cases of cervical adenocarcinoma
      and mesonephric carcinoma were positive for p16(INK4a). CONCLUSION: p16(INK4a) is
      a useful additional marker for interpretation of problematic Pap smears and
      reduces the variability during evaluation of suspicious biopsies of the uterine
      cervix.

PMID- 19596141
TI  - Does access to care equal asthma control in school-age children?

PMID- 19596142
TI  - Similar colds in subjects with allergic asthma and nonatopic subjects after
      inoculation with rhinovirus-16.
AB  - BACKGROUND: Rhinovirus infections are frequent causes of asthma exacerbations.
      OBJECTIVE: This study was conducted to test whether subjects with and without
      allergic asthma have different responses to infection and to identify baseline
      patient risk factors that predict cold outcomes. METHODS: Twenty subjects with
      mild persistent allergic asthma and 18 healthy subjects were experimentally
      inoculated with rhinovirus-16. Subjects were evaluated at baseline, during the
      acute infection, and during recovery for asthma and cold symptoms by using a
      validated questionnaire. Sputum and nasal lavage fluid were evaluated for viral
      shedding, cytokines, and cellular inflammation. RESULTS: There were no group
      specific significant differences in peak cold symptom scores (10.0 +/- 5.8 vs
      11.1 +/- 6.2, asthmatic vs healthy subjects), peak nasal viral titers (log(10)
      4.3 +/- 0.8 vs 3.7 +/- 1.4 50% tissue culture infective dose/mL, respectively),
      or changes in peak flow during the study (10% +/- 10% vs 8% +/- 6%,
      respectively). Rhinovirus-16 infection increased peak asthma index values in the
      asthmatic group (median, 6 --> 13; P = .003) but only marginally in the healthy
      group (median, 4 --> 7; P = .09). More asthmatic subjects had detectable
      eosinophils in nasal lavage and sputum samples at baseline and during infection,
      but otherwise, cellular and cytokine responses were similar. Baseline sputum
      eosinophilia and CXCL8 (IL-8) levels were positively associated with cold
      symptoms, whereas CCL2 (monocyte chemotactic protein 1) levels were inversely
      associated with nasal viral shedding. CONCLUSIONS: These findings suggest that
      subjects with mild allergic asthma and healthy subjects have similar cold
      symptoms and inflammatory and antiviral responses. In addition, eosinophilia and
      other selective baseline measures of airway inflammation in subjects with or
      without asthma might predict respiratory outcomes with rhinovirus infection.

PMID- 19596143
TI  - Relevance of IgE binding to short peptides for the allergenic activity of food
      allergens.
AB  - BACKGROUND: Analysis of IgE antibody binding to epitopes provides information for
      food allergy diagnosis and management and construction of hypoallergenic
      candidate vaccines, but the contribution of sequential epitopes to functionally
      relevant IgE binding is not fully understood. OBJECTIVES: We sought to study the
      impact of IgE-binding peptides described as major sequence epitopes in the
      literature on IgE-binding capacity of 2 selected food allergens. METHODS: IgE
      binding peptides of the food allergens Ara h 2 (peanut) and Pen a 1 (shrimp) were
      identified. Synthetic soluble peptides representing the identified sequences were
      assessed for their capacity to inhibit IgE binding to the parent allergens by
      means of ELISA and in mediator release assay. The IgE-binding capacity of
      unfolded recombinant (r) Ara h 2 was analyzed. A hybrid tropomyosin carrying the
      IgE-binding regions of Pen a 1 grafted into the structural context of the
      nonallergenic mouse tropomyosin was applied in ELISA inhibition experiments and
      ImmunoCAP analysis. RESULTS: Although IgE-binding peptides representing sections
      of the allergen sequences were detected, no relevant capacity to inhibit the IgE
      binding to the parent allergen in ELISA or basophil activation test was observed.
      Unfolded rAra h 2 showed reduced IgE-binding capacity compared with folded rAra h
      2 and failed to elicit mediator release. Hybrid tropomyosin bound less IgE than
      rPen a 1 in ImmunoCAP analysis and revealed marginal inhibitory capacity.
      CONCLUSION: Peptides identified as major sequence epitopes on Pen a 1 and Ara h 2
      show little contribution to the IgE binding of the allergens studied.

PMID- 19596144
TI  - Managing asthma and allergies in schools: an opportunity to coordinate health
      care.
AB  - Children spend a great deal of time in school and can be exposed to situations
      that increase their risk for an asthma exacerbation or a reaction to food. As
      such, the clinician can play a significant role in educating children, their
      families, and school personnel about principles that can be applied not only to
      manage reactions when they occur but also to prevent them. This theme issue will
      provide information on indoor allergens commonly present in school and day care
      settings, as well as information on how to manage children with asthma and food
      allergies in these settings.

PMID- 19596145
TI  - Audit of manufactured products: use of allergen advisory labels and
      identification of labeling ambiguities.
AB  - BACKGROUND: The Food Allergy Labeling and Consumer Protection Act became
      effective January 1, 2006, and mandates disclosure of the 8 major allergens in
      plain English and as a source of ingredients in the ingredient statement. It does
      not regulate advisory labels. OBJECTIVE: We sought to determine the frequency and
      language used in voluntary advisory labels among commercially available products
      and to identify labeling ambiguities affecting consumers with allergy. METHODS:
      Trained surveyors performed a supermarket survey of 20,241 unique manufactured
      food products (from an original assessment of 49,604 products) for use of
      advisory labels. A second detailed survey of 744 unique products evaluated
      additional labeling practices. RESULTS: Overall, 17% of 20,241 products surveyed
      contain advisory labels. Chocolate candy, cookies, and baking mixes were the 3
      categories of 24 with the greatest frequency (> or = 40%). Categorically,
      advisory warnings included "may contain" (38%), "shared equipment" (33%), and
      "within plant" (29%). The subsurvey disclosed 25 different types of advisory
      terminology. Nonspecific terms, such as "natural flavors" and "spices," were
      found on 65% of products and were not linked to a specific ingredient for 83% of
      them. Additional ambiguities included unclear sources of soy (lecithin vs
      protein), nondisclosure of sources of gelatin and lecithin, and simultaneous
      disclosure of "contains" and "may contain" for the same allergen, among others.
      CONCLUSION: Numerous products have advisory labeling and ambiguities that present
      challenges to consumers with food allergy. Additional allergen labeling
      regulation could improve safety and quality of life for individuals with food
      allergy.

PMID- 19596146
TI  - Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of
      obesity and hypoxia.
AB  - BACKGROUND: Low-grade inflammation may potentially explain the relationship
      between obstructive sleep apnea syndrome (OSA) and cardiovascular events.
      However, the respective contribution of intermittent hypoxia and confounders,
      such as obesity, is still debated. OBJECTIVES: To monitor urinary leukotriene
      E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene
      production, in OSA; to determine the influence of obesity and other confounders
      on U-LTE(4) concentrations; to examine the mechanisms involved through
      transcriptional profiling of the leukotriene pathway in peripheral blood
      mononuclear cells (PBMCs); and to investigate the effect of continuous positive
      air pressure (CPAP) on U-LTE(4) concentrations. METHODS: We measured U-LTE(4) by
      liquid chromatography-tandem mass spectrometry. RESULTS: The U-LTE(4)
      concentrations were increased (P = .019) in 40 nonobese patients with OSA
      carefully matched for age, sex, and body mass index (BMI) to 25 control subjects,
      and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean
      oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA
      (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In
      those patients, the expression levels of 5-lipoxygenase activating protein mRNA
      in mononuclear cells exhibited a similar pattern. A stepwise multiple linear
      regression analysis performed in this cohort identified BMI (P = .001; regression
      coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001;
      regression coefficient, 1.01) as independent predictors of U-LTE(4)
      concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4)
      concentrations only in patients with OSA with normal BMI. CONCLUSION: Obesity,
      and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production
      in patients with OSA.

PMID- 19596147
TI  - The life skills program IPSY: positive influences on school bonding and
      prevention of substance misuse.
AB  - The present study investigated whether a life skills program (LSP) for the
      prevention of adolescent substance misuse can have positive influences on a
      school context and on school bonding. The study also explored whether effects on
      alcohol use are mediated by positive effects on school bonding resulting from
      program participation. The LSP IPSY (Information+Psychosocial
      Competence=Protection) was implemented over a 3-year period via specially trained
      teachers. Analyses were based on a German evaluation study utilizing a quasi
      experimental design (intervention/control) with school-wise assignment to the
      respective groups. Analyses were based on four measurement points (N=952, 10
      years at pre-test). Results indicated that IPSY was well implemented, highly
      accepted by teachers and students, and that teachers profited regarding their
      teaching methods. ANCOVAS revealed positive program effects on alcohol use and
      school bonding. Multiple regressions indicated that positive influences on school
      bonding following program participation partially mediated effects on alcohol
      use.

PMID- 19596148
TI  - Value transmissions between parents and children: gender and developmental phase
      as transmission belts.
AB  - This study applied the gender role model of socialization theory, the
      developmental aging theory, and the topic salience perspective to the
      investigation of parent-child value transmissions. Specifically, we examined
      whether the bi-directionality and selectivity of value transmissions differed as
      a function of parents' and children's gender and children's developmental phase
      (adolescence versus emerging adulthood). Transmissions between parents and
      children from 402 Dutch families on the topics of work as duty and hedonism were
      studied across a 5-year period using structural equation modeling. As expected,
      we did not find convincing support for the general models of gender socialization
      and developmental aging. Instead, parent-child value transmissions appeared to be
      qualified by value salience. Particularly, high salience of work as duty for
      fathers was related with great paternal involvement in transmissions on this
      value orientation and high salience of hedonism for sons and adolescents was
      linked to transmissions from these groups to parents.

PMID- 19596149
TI  - Organic matter characterisation and turnover in the sediment and seawater of a
      tourist harbour.
AB  - A survey of a Ligurian tourist harbour was carried out during winter 2006 and
      summer 2007 in order to study the organic matter (OM) turnover through
      extracellular enzymatic activity. Seawater and sediments were sampled at six
      stations, three inside the port boundaries, one outside the port and two in an
      area influenced by the outflow of a minor river (Boate). The seawater showed OM
      turnover times similar to other oligo-mesotrophic coastal areas, and low
      concentrations of chlorophyll-a and inorganic nutrients. The sediments, instead,
      revealed high OM loads and a predominance of proteolysis. A significant reduction
      of the OM loads was observed in the outside station, indicating that the OM
      accumulation was due to the structures and activities of the harbour and to the
      Boate influence. The OM biotic recycling via enzymatic activity was enhanced
      especially during summer. Although the carbohydrates were probably highly
      refractory, their turnover was notably faster, due to glycolytic enzymatic
      activity that was enhanced more than the proteolytic in both the sediment and in
      the seawater. This suggested that the removal and recycling of OM were
      potentially efficient, and prevented the shift to eutrophication of the Rapallo
      harbour area.

PMID- 19596150
TI  - Mechanical properties, drug eluting characteristics and in vivo performance of a
      genipin-crosslinked chitosan polymeric stent.
AB  - A limitation with the use of polymers as stent matrices is their inherent
      mechanical weakness. In this study, a polymeric stent, made from chitosan-based
      films fixed by genipin which has a cyclic molecular structure, was developed (the
      genipin stent). The mechanical properties of the genipin stent were investigated;
      its counterpart fixed by a linear epoxy compound (the epoxy stent) and a
      commercially available metallic stent were used as controls. The results
      indicated that the cyclic crosslinking structures formed within the genipin stent
      matrix were beneficiary to the improvement of its mechanical property.
      Additionally, the tolerable compression load of the genipin stent was superior to
      that of the control metallic stent. The cytotoxicity of the genipin stent was
      significantly lower than the epoxy stent. The deployment of the genipin stent in
      rabbit infrarenal abdominal aortas was performed using a French sheath. At 3
      months postoperatively, the retrieved arteries remained patent; no thrombosis was
      observed. A nearly intact layer of endothelial cells was seen on the stent
      implanted vessel wall. To evaluate its possibility as a drug delivery vehicle,
      sirolimus (an anti-proliferative drug) was loaded in the genipin stent. It was
      found that the genipin stent with heparin coating exhibited a linear sustained
      release profile and the released sirolimus still possessed its original activity
      in inhibiting smooth muscle cell proliferation. These findings suggest that the
      genipin stent with enhanced mechanical strength can be used as an attractive
      stent platform for local drug delivery.

PMID- 19596151
TI  - Synthesis and characterization of iodinated polyurethane with inherent
      radiopacity.
AB  - The synthesis and characterization of polyurethane (PU) with excellent
      radiopacity for medical and allied applications are reported. Bisphenol-A (BPA)
      was iodinated to obtain 4,4'-isopropylidinedi-(2,6-diiodophenol) (IBPA) which was
      used as a chain extender for the preparation of a radiopaque PU. The PU was
      prepared by reacting 4,4'-methylenebis(phenyl isocyanate) (MDI),
      poly(tetramethylene glycol) (PTMG) and IBPA in 2.2:1.2:1 molecular ratio and is
      characterized by infrared spectroscopy (IR), thermogravimetry (TGA), dynamic
      mechanical analysis (DMA), energy dispersive X-ray analysis (EDX), gel permeation
      chromatography (GPC) and X-radiography. X-ray images showed that the PU prepared
      using IBPA as the chain extender is highly radiopaque. An in vitro cytotoxicity
      test using L929 mouse fibroblast cells shows that the PU is non-cytotoxic. The
      outlined synthesis of a PU with radiocontrast properties opens up the possibility
      of synthesizing many different kinds of radiopaque PUs with desirable range of
      physical properties exploiting the versatility in their chemical synthesis.

PMID- 19596152
TI  - The use of reactive polymer coatings to facilitate gene delivery from poly
      (epsilon-caprolactone) scaffolds.
AB  - To functionalize biomaterials for bioconjugation, a chemical vapor deposition
      (CVD) polymerization technique was utilized to modify material surfaces. Poly [(4
      amino-p-xylylene)-co-(p-xylylene)] (PPX-NH(2)) was deposited on inert
      polycaprolactone (PCL) surfaces to provide a reactive amine layer on the
      substrate surfaces. The biocompatibility of PPX-NH(2) was evaluated by 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) and lactate dehydrogenase (LDH) assays. The results demonstrated that cells
      continuously proliferated on CVD treated PCL surfaces with high survival rates.
      Biotin was conjugated on modified PCL surfaces to immobilize avidin for binding
      of biotinylated adenovirus. Scanning electron microscopy (SEM) examination
      illustrated that adenoviruses were evenly bound on both 2-D films and 3-D
      scaffolds, suggesting CVD was capable of modifying various substrates with
      different geometries. Using a wax masking technique, the biotin conjugation was
      controlled to immobilize avidin on specific sites. Due to the virus binding
      specificity on CVD-modified surfaces, cell transduction was restricted to the
      pattern of immobilized virus on biomaterials, by which transduced and non
      transduced cells were controlled in different regions with a distinct interface.
      Because CVD was functional in different hierarchies, this surface modification
      should be able to custom-tailor bioconjugation for different applications.

PMID- 19596154
TI  - Elevated anticardiolipin antibodies in schizophrenic patients before and during
      neuroleptic medication.
AB  - The objective of this study was to examine the prevalence of IgG and IgM
      anticardiolipin antibodies (aCL) in schizophrenic patients and to determine the
      relation of aCL levels with neuroleptic medication and psychotic symptoms. Twenty
      three patients with acute episodes of chronic schizophrenia, drug-free for at
      least 3 months before entering the study, were tested for aCL at admission (T1)
      and 42 days (T2) after neuroleptic treatment started. Blood samples were taken
      from 20 healthy volunteers as well. Diagnosis was performed according to DSM-IV.
      Serum samples were analysed for IgG and IgM autoantibodies against beta2
      glycoprotein-1-cardiolipin complex by commercially available ELISA kits (Binding
      site, UK). Significantly higher levels of aCL antibodies of both isotypes were
      found in schizophrenic patients versus controls. In patients IgM-aCL positivity
      was significantly more frequent than in controls. The elevated IgM-aCL and IgG
      aCL values were not associated with neuroleptic treatment and psychotic symptoms,
      as measured by the Positive and Negative Syndrome Scale and the Pentagonal
      Structural Model of Schizophrenic Symptoms. The negative correlation of IgM-aCL
      and IgG-aCL with the positive symptoms scale and the autistic preoccupation scale
      (Pentagonal Structural Model) may indicate the consumption of these antibodies in
      the exacerbation of the disease.

PMID- 19596155
TI  - Do comorbid anxiety disorders impact treatment planning for outpatients with
      major depressive disorder?
AB  - Research indicates that depressed patients with comorbid anxiety disorders have a
      poorer long-term course of illness, are less responsive to treatment, and may
      experience greater deficits in psychosocial functioning, when compared with
      depressed patients without comorbid anxiety disorders. The objective of this
      study was to examine, through use of a large, well-characterized clinical
      database, how clinicians may modify treatment recommendations in depressed
      outpatients when anxiety disorders are present. A group of 346 case records,
      derived from the Methods to Improve Diagnostic Assessment and Services (MIDAS)
      project at Rhode Island Hospital, were examined to determine what treatment
      recommendations were made immediately after diagnosis. Psychopharmacological and
      psychotherapeutic treatments were classified to capture differences in
      recommendations between groups. Demographic and clinical characteristics were
      compared for patients with (n=248) and without (n=98) comorbid anxiety disorders.
      Utilizing logistic regression models, we found patients with anxiety disorders
      had a greater number of psychopharmacological therapies included as part of their
      initial treatment plan, but no differences were found in initial
      psychotherapeutic interventions. Our results indicate that practitioners are
      making unique recommendations based on comorbid anxiety diagnoses, but outcome
      studies are now needed to determine the most effective treatment methods for this
      patient population.

PMID- 19596153
TI  - Understanding human aggression: New insights from neuroscience.
AB  - The present paper reviews and summarizes the basic findings concerning the nature
      of the neurobiological and behavioral characteristics of aggression and rage. For
      heuristic purposes, the types of aggression will be reduced to two categories -
      defensive rage (affective defense) and predatory attack. This approach helps
      explain both the behavioral properties of aggression as well as the underlying
      neural substrates and mechanisms of aggression both in animals and humans.
      Defensive rage behavior is activated by a threatening stimulus that is real or
      perceived and is associated with marked sympathetic output. This yields
      impulsivity with minimal cortical involvement. Predatory attack behavior in both
      animals and humans is generally planned, taking minutes, hours, days, weeks,
      months, or even years (with respect to humans) for it to occur and is directed
      upon a specific individual target; it reflects few outward sympathetic signs and
      is believed to require cortical involvement for its expression. Predatory attack
      requires activation of the lateral hypothalamus, while defensive rage requires
      activation of the medial hypothalamus and midbrain periaqueductal gray (PAG).
      Both forms of aggressive behavior are controlled by components of the limbic
      system, a region of the forebrain that is influenced by sensory inputs from the
      cerebral cortex and monoaminergic inputs from the brainstem reticular formation.
      Control of aggressive tendencies is partly modifiable through conditioning and
      related learning principles generated through the cerebral cortex.

PMID- 19596157
TI  - Severe thrombocytopenia complicating giant left atrial rhabdomyosarcoma.
AB  - We report an adult patient with a large left atrial rhabdomyosarcoma causing
      intracardiac blood flow obstruction and thrombocytopenia, in whom platelet count
      normalized after surgical excision of the tumor. The patient presented a fatal
      intracranial hemorrhage 2 weeks after surgery.

PMID- 19596158
TI  - Dosimetry audit for a multi-centre IMRT head and neck trial.
AB  - BACKGROUND AND PURPOSE: PARSPORT was a multi-centre randomised trial in the UK
      which compared Intensity-Modulated Radiotherapy (IMRT) and conventional
      radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit
      goals were to verify the plan delivery in participating centres, ascertain what
      tolerances were suitable for head and neck IMRT trials and develop an IMRT
      credentialing program. MATERIALS AND METHODS: Centres enrolling patients
      underwent rigorous quality assurance before joining the trial. Following this
      each centre was visited for a dosimetry audit, which consisted of treatment
      planning system tests, fluence verification films, combined field films and dose
      point measurements. RESULTS: Mean dose point measurements were made at six
      centres. For the primary planning target volume (PTV) the differences with the
      planned values for the IMRT and CRT arms were -0.6% (1.8% to -2.4%) and 0.7%
      (2.0% to -0.9%), respectively. Ninety-four percent of the IMRT fluence films for
      individual fields passed gamma criterion of 3%/3mm and 75% of the films for
      combined fields passed gamma criterion 4%/3mm (no significant difference between
      dynamic delivery and step and shoot delivery). CONCLUSIONS: This audit suggests
      that a 3% tolerance could be applied for PTV point doses. For dose distributions
      tolerances of 3%/3mm on individual fields and 4%/3mm for combined fields are
      proposed for multi-centre head and neck IMRT trials.

PMID- 19596159
TI  - Determining floodplain sedimentation rates using 137Cs in a low fallout
      environment dominated by channel- and cultivation-derived sediment inputs,
      central Queensland, Australia.
AB  - Fallout (137)Cs has been widely used to determine floodplain sedimentation rates
      in temperate environments, particularly in the northern hemisphere. Its
      application in low fallout, tropical environments in the southern hemisphere has
      been limited. In this study we assess the utility of (137)Cs for determining
      rates of floodplain sedimentation in a dry-tropical catchment in central
      Queensland, Australia. Floodplain and reference site cores were analysed in two
      centimetre increments, depth profiles were produced and total (137)Cs inventories
      calculated from the detailed profile data. Information on the rates of (137)Cs
      migration through local soils was obtained from the reference site soil cores.
      This data was used in an advection-diffusion model to account of (137)Cs mobility
      in floodplain sediment cores. This allowed sedimentation rates to be determined
      without the first year of detection for (137)Cs being known and without having to
      assume that (137)Cs remains immobile following deposition. Caesium-137 depth
      profiles in this environment are demonstrated to be an effective way of
      determining floodplain sedimentation rates. The total (137)Cs inventory approach
      was found to be less successful, with only one of the three sites analysed being
      in unequivocal agreement with the depth profile results. The input of sediment
      from catchment sources that have little, or no, (137)Cs attached results in true
      depositional sites having total inventories that are not significantly different
      from those of undisturbed reference sites.

PMID- 19596160
TI  - Vertical distribution of organochlorine pesticides in humus along Alpine
      altitudinal profiles in relation to ambiental parameters.
AB  - In forest soils along vertical profiles located in different parts of the Alps,
      concentrations of persistent organic pollutants (POPs), namely organochlorine
      pesticides (OCPs) like dichlorodiphenyltrichloroethanes (DDTs), hexachlorobenzene
      (HCB), hexachlorocyclohexanes (HCH), heptachlor, aldrin, dieldrin and mirex, were
      measured. Though local characteristics of the sites are influenced by numerous
      factors like orographic and meteorological parameters, forest stand
      characteristics and humus parameters, we ascertained a marked vertical increase
      of concentrations of some organochlorine compounds in the soil. On the basis of
      climatological values of each site, we found that the contamination increase with
      altitude can be ascribed to a certain 'cold condensation effect'. In addition,
      the perennial atmospheric deposition of POPs is controlled by precipitation.
      Other key parameters explaining the accumulation of POPs are the soil organic
      carbon stocks, the turnover times, the re-volatilisation and degradation
      processes, which vary with altitude.

PMID- 19596161
TI  - Arsenic species in ecosystems affected by arsenic-rich spring water near an
      abandoned mine in Korea.
AB  - The objectives of this study were to quantitatively estimate the distribution of
      arsenic with its speciation and to identify potential pathways for transformation
      of arsenic species from samples of water, sediments, and plants in the ecosystem
      affected by the Cheongog Spring, where As(V) concentration reached levels up to
      0.270 mg L(-1). After flowing about 100 m downstream, the arsenic level showed a
      marked reduction to 0.044 mg L(-1) (about 84% removal) without noticeable changes
      in major water chemistry. The field study and laboratory hydroponic experiments
      with the dominant emergent plants along the creek (water dropwort and thunbergian
      smartweed) indicated that arsenic distribution, reduction, and speciation appear
      to be controlled by, (i) sorption onto stream sediments in exchangeable
      fractions, (ii) bioaccumulation by and possible release from emergent plants, and
      (iii) transformation of As(V) to As(III) and organic species through biological
      activities.

PMID- 19596162
TI  - Recognizing and reacting to product-related adverse events in hemodialysis.

PMID- 19596165
TI  - Improving poor women's access to maternity care: Findings from a primary care
      intervention in Burkina Faso.
AB  - To date, there has been little progress in reducing wealth inequities in access
      to maternity care. This paper describes the results of a maternal health
      intervention in Burkina Faso that was aimed at increasing access to skilled
      maternity care by improving availability and quality of maternity care,
      particularly at primary care health facilities, and promoting its use before,
      during, and after delivery. Post-intervention data show a large overall increase
      in use of facility-based maternity care in the intervention district,
      particularly at primary care facilities, but little change in the comparison
      district. In addition, large wealth inequities in the use of professional care
      during childbirth were almost eliminated in the intervention district while they
      increased in the comparison district-both among all women, and among the subset
      of women who reported experiencing complications during delivery. Study results
      suggest that efforts to upgrade maternity services at primary care facilities may
      be key for improving poor women's access to and use of skilled care during
      childbirth.

PMID- 19596167
TI  - HIV prevention while the bulldozers roll: exploring the effect of the demolition
      of Goa's red-light area.
AB  - Interventions targeting sex-workers are pivotal to HIV prevention in India.
      Community mobilisation is considered by the National AIDS Control Programme to be
      an integral component of this strategy. Nevertheless societal factors, and
      specifically policy and legislation around sex-work, are potential barriers to
      widespread collectivisation and empowerment of sex-workers. Between November 2003
      and December 2005 we conducted participatory observation and rapid ethnographic
      mapping with several hundred brief informant interviews, in addition to 34 semi
      structured interviews with key-informants, 16 in-depth interviews with female sex
      workers, and 3 focus-group-discussions with clients and mediators. This provides
      a detailed examination of the demolition of Baina, one of India's large red-light
      areas, in 2004, and one of the first accounts of the effect of dismantling the
      red-light area on the organisation of sex-work and sex-workers' sexual risk. The
      results suggest that the concentrated and homogeneous brothel-based sex-work
      environment rapidly evolved into heterogeneous, clandestine and dispersed modes
      of operation. The social context of sex-work that emerged from the dust of the
      demolition was higher risk and less conducive to HIV prevention. The demolition
      acted as a negative structural intervention; a catastrophic event that fragmented
      sex-workers' collective identity and agency and rendered them voiceless and
      marginalised. The findings suggest that an abolitionist approach to sex-work and
      legislation or policy that either criminalises this large group of women, or
      renders them as invisible victims, will increase the stigma and exclusion they
      experience. For the targeted HIV prevention approaches advocated by the National
      AIDS Control Programme to be effective, there is a need for legislation and
      policy that supports sex-workers' agency and self-organisation and enables them
      to create a safer working environment for themselves.

PMID- 19596163
TI  - Oral paricalcitol in the treatment of patients with CKD and proteinuria: a
      randomized trial.
AB  - BACKGROUND: Vitamin D has key roles in regulating systems that could be important
      in the pathobiological state of proteinuria. Because of this, it could be helpful
      in treating patients with proteinuric renal diseases. The objective is to
      determine the effect of oral paricalcitol on protein excretion in patients with
      proteinuric chronic kidney disease. STUDY DESIGN: Double-blind randomized study.
      SETTING & PARTICIPANTS: 61 patients with estimated glomerular filtration rate of
      15 to 90 mL/min/1.73 m(2) and protein excretion greater than 400 mg/24 h.
      INTERVENTION: Randomization to 6 months of treatment with paricalcitol, 1 mug/d,
      or placebo. OUTCOMES & MEASUREMENTS: The predefined primary end point was to
      compare change in mean spot urinary protein-creatinine ratio between the baseline
      measurement and the last study evaluation (6 months in study completers) between
      the 2 groups. Every 4 weeks, there was measurement of serum intact parathyroid
      hormone, serum calcium, serum phosphorus, serum creatinine, and urine spot
      protein and creatinine. RESULTS: At baseline, mean urinary protein-creatinine
      ratios were 2.6 and 2.8 g/g in the placebo and paricalcitol groups, respectively.
      At final evaluation, mean ratios were 2.7 and 2.3, respectively. Changes in
      protein excretion from baseline to last evaluation were +2.9% for controls and 
      17.6% for the paricalcitol group (P = 0.04). A 10% decrease in proteinuria
      occurred in controls (7 of 27; 25.9%) and the paricalcitol group (16 of 28;
      57.1%; P = 0.03). LIMITATIONS: The relatively small sample size limits the extent
      to which results should be generalized. CONCLUSIONS: Paricalcitol resulted in a
      significant reduction in protein excretion in patients with proteinuric renal
      disease.

PMID- 19596168
TI  - Complex sleep apnea and obesity hypoventilation syndrome. Opposite ends of the
      spectrum of obstructive sleep apnea?
AB  - In most cases, the application of continuous positive airway pressure (CPAP)
      during sleep in patients affected by obstructive sleep apnea (OSA) eliminates
      upper airway obstruction and makes breathing stable and regular. However, some
      OSA patients develop periodic breathing and central apneas during CPAP
      administration, a finding that has been labelled as "complex sleep apnea"
      (complex SA). Such breathing disorder may occur only acutely after CPAP treatment
      initiation or sometimes persist with chronic CPAP treatment. We hypothesize that
      complex SA may be the consequence of mechanisms analogous to those leading to
      obesity hypoventilation syndrome (OHS), but operating in an opposite direction.
      Periodic breathing is one of the factors predisposing to OSA and is an essential
      factor for the recurrence of central apneas in normo or hypocapnic patients. A
      high ventilatory responsiveness to chemical stimuli enhances breathing
      periodicity. In subjects with periodic central apneas chemoresponsiveness is
      high, while in subjects with OSA it spans throughout a wide range, and is
      correlated to diurnal blood gas levels. In fact, sleep respiratory disorders may
      be responsible for either an augmentation in ventilatory responses to chemical
      stimuli consequent to chronic exposure to intermittent hypoxia, or for a decrease
      in ventilatory responses when prolonged exposure to hypercapnia is experienced.
      Among OSA subjects, those with OHS show very depressed hypercapnic responses.
      After chronic OSA treatment, ventilatory responses to chemical stimuli may either
      decrease, in previously hyperresponsive subjects, or increase, in previously
      hyporesponsive subjects. Most patients with OHS decrease daytime PCO(2) levels
      and increase their ventilatory responses after chronic CPAP treatment. Complex SA
      could appear in those OSA subjects in whom chronic exposure to nocturnal
      respiratory disorders leads to the highest responsiveness to chemical stimuli,
      and could disappear after blunting of ventilatory responses following chronic
      CPAP treatment. Complex SA may be one extreme of evolutionary spectrum of OSA,
      the opposite end being represented by OHS.

PMID- 19596166
TI  - Perceived job insecurity and worker health in the United States.
AB  - Economic recessions, the industrial shift from manufacturing toward service
      industries, and rising global competition have contributed to uncertainty about
      job security, with potential consequences for workers' health. To address
      limitations of prior research on the health consequences of perceived job
      insecurity, we use longitudinal data from two nationally-representative samples
      of the United States population, and examine episodic and persistent perceived
      job insecurity over periods of about three years to almost a decade. Results show
      that persistent perceived job insecurity is a significant and substantively
      important predictor of poorer self-rated health in the American's Changing Lives
      (ACL) and Midlife in the United States (MIDUS) samples, and of depressive
      symptoms among ACL respondents. Job losses or unemployment episodes are
      associated with perceived job insecurity, but do not account for its association
      with health. Results are robust to controls for sociodemographic and job
      characteristics, negative reporting style, and earlier health and health
      behaviors.

PMID- 19596169
TI  - Surgical clips assist in the visualization of the lumpectomy cavity in three
      dimensional conformal accelerated partial-breast irradiation.
AB  - PURPOSE: To determine to what extent the placement of surgical clips helps
      delineate the cavity in three-dimensional conformal accelerated partial-breast
      irradiation. PATIENTS AND METHODS: Planning CT images of 100 lumpectomy cavities
      were reviewed in a cohort of 100 consecutive patients. The cavities were
      determined and categorized by two radiation oncologists according to cavity
      visualization score criteria and the breast density score. The two physicians
      first attempted to delineate the lumpectomy cavity without clips and then with
      clips. RESULTS: In the case of high-density mammary tissue, the breast remodeling
      done during surgery does not enable the lumpectomy cavity to be sufficiently
      visualized. The use of surgical clips significantly improved the ability to
      visualize the lumpectomy cavity, with a 69% rate of concordance between
      physicians regardless of the breast tissue density. CONCLUSION: The placement of
      surgical clips at lumpectomy enables visualization of the lumpectomy cavity and
      allows upgrading of the cavity visualization score on CT scans obtained for
      accelerated partial-breast irradiation treatment planning.

PMID- 19596170
TI  - Hypothyroidism after radiotherapy for nasopharyngeal cancer patients.
AB  - PURPOSE: The aim of this study was to determine the long-term incidence and
      possible predictive factors for posttreatment hypothyroidism in nasopharyngeal
      carcinoma (NPC) patients after radiotherapy. METHODS AND MATERIALS: Four hundred
      and eight sequential NPC patients who had received regular annual thyroid hormone
      surveys prospectively after radiotherapy were included in this study. Median
      patient age was 47.3 years, and 286 patients were male. Thyroid function was
      prospectively evaluated by measuring thyroid-stimulating hormone (TSH) and serum
      free thyroxine (FT4) levels. Low FT4 levels indicated clinical hypothyroidism in
      this study. RESULTS: With a median follow-up of 4.3 years (range, 0.54-19.7
      years), the incidence of low FT4 level was 5.3%, 9.0%, and 19.1% at 3, 5, and 10
      years after radiotherapy, respectively. Hypothyroidism was more common with early
      T stage (p = 0.044), female sex (p = 0.037), and three-dimensional conformal
      therapy with the altered fractionation technique (p = 0.005) after univariate
      analysis. N stage, chemotherapy, reirradiation, and neck electron boost did not
      affect the incidence of hypothyroidism. Younger age and conformal therapy were
      significant factors that determined clinical hypothyroidism after multivariate
      analysis. Overall, patients presented with a low FT4 level about 1 year after
      presenting with an elevated TSH level. CONCLUSION: Among our study group of NPC
      patients, 19.1% experienced clinical hypothyroidism by 10 years after treatment.
      Younger age and conformal therapy increased the risk of hypothyroidism. We
      suggest routine evaluation of thyroid function in NPC patients after
      radiotherapy. The impact of pituitary injury should be also considered.

PMID- 19596171
TI  - Involved-node and involved-field volumetric modulated arc vs. fixed beam
      intensity-modulated radiotherapy for female patients with early-stage supra
      diaphragmatic Hodgkin lymphoma: a comparative planning study.
AB  - PURPOSE: A comparative treatment planning study was performed to compare
      volumetric-modulated arc (RA) to conventional intensity modulated (IMRT) for
      involved-field (IFRT) and involved-node (INRT) radiotherapy for Hodgkin lymphoma
      (HL). METHODS AND MATERIALS: Plans for 10 early-stage HL female patients were
      computed for RA and IMRT. First, the planning target volume (PTV) coverage and
      organs at risk (OAR) dose deposition was assessed between the two modalities.
      Second, the OAR (lung, breast, heart, thyroid, and submandibular gland) dose
      volume histograms were computed and compared for IFRT and INRT, respectively.
      RESULTS: For IFRT and INRT, PTV coverage was equally homogeneous with both RA and
      IMRT. By and large, the OAR irradiation with IFRT planning was not significantly
      different between RA and IMRT. For INRT, doses computed for RA were, however,
      usually lower than those with IMRT, particularly so for the lung, breast, and
      thyroid. Regardless of RA and IMRT modalities, a significant 20-50% decrease of
      the OAR computed mean doses was observed with INRT when compared with IFRT
      (Breast D(Mean) 1.5 +/- 1.1 vs. 2.6 +/- 1.7 Gy, p < 0.01 and 1.6 +/- 1.1 vs. 2.9
      +/- 1.9 Gy, p < 0.01 for RA and IMRT, respectively). CONCLUSIONS: RA and IMRT
      results in similar level of dose homogeneity. With INRT but not IFRT planning,
      the computed doses to the PTV and OAR were usually higher and lower with RA when
      compared to IMRT. Regardless of the treatment modality, INRT when compared with
      IFRT planning led to a significant decrease in OAR doses, particularly so for the
      breast and heart.

PMID- 19596172
TI  - Quantitative assessment of image-guided radiotherapy for paraspinal tumors.
AB  - PURPOSE: To evaluate stereotactic positioning uncertainties of patients with
      paraspinal tumors treated with fractionated intensity-modulated radiotherapy; and
      to determine whether target-point correction via rigid registration is sufficient
      for daily patient positioning. PATIENTS AND METHODS: Forty-five patients with
      tumors at the cervical, thoracic, and lumbar spine received regular control
      computed-tomography (CT) scans using an in-room CT scanner. All patients were
      immobilized with the combination of Scotch cast torso and head masks. The
      positioning was evaluated regarding translational and rotational errors by
      applying a rigid registration algorithm based on mutual information. The
      registration box was fitted to the target volume for optimal registration in the
      high-dose area. To evaluate the suitability of the rigid registration result for
      correcting the target volume position we subsequently registered three small
      subsections of the upper, middle, and lower target volume. The resulting residual
      deviations reflect the extent of the elastic deformations, which cannot be
      covered by the rigid-body registration procedure. RESULTS: A total of 321 control
      CT scans were evaluated. The rotational errors were negligible. Translational
      errors were smallest for cervical tumors (-0.1 +/- 1.1, 0.3 +/- 0.8, and 0.1 +/-
      0.9 mm along left-right, anterior-posterior, and superior-inferior axes),
      followed by thoracic (0.8 +/- 1.1, 0.3 +/- 0.8, and 1.1 +/- 1.3 mm) and lumbar
      tumors (-0.7 +/- 1.3, 0.0 +/- 0.9, and 0.5 +/- 1.6 mm). The residual deviations
      of the three subsections were <1 mm. CONCLUSIONS: The applied stereotactic
      patient setup resulted in small rotational errors. However, considerable
      translational positioning errors may occur; thus, on the basis of these data
      daily control CT scans are recommended. Rigid transformation is adequate for
      correcting the target volume position.

PMID- 19596173
TI  - Tumor-volume simulation during radiotherapy for head-and-neck cancer using a four
      level cell population model.
AB  - PURPOSE: To develop a fast computational radiobiologic model for quantitative
      analysis of tumor volume during fractionated radiotherapy. The tumor-volume model
      can be useful for optimizing image-guidance protocols and four-dimensional
      treatment simulations in proton therapy that is highly sensitive to physiologic
      changes. METHODS: The analysis is performed using two approximations: (1) tumor
      volume is a linear function of total cell number and (2) tumor-cell population is
      separated into four subpopulations: oxygenated viable cells, oxygenated lethally
      damaged cells, hypoxic viable cells, and hypoxic lethally damaged cells. An
      exponential decay model is used for disintegration and removal of oxygenated
      lethally damaged cells from the tumor. RESULTS: We tested our model on daily
      volumetric imaging data available for 14 head-and-neck cancer patients treated
      with an integrated computed tomography/linear accelerator system. A simulation
      based on the averaged values of radiobiologic parameters was able to describe
      eight cases during the entire treatment and four cases partially (50% of
      treatment time) with a maximum 20% error. The largest discrepancies between the
      model and clinical data were obtained for small tumors, which may be explained by
      larger errors in the manual tumor volume delineation procedure. CONCLUSIONS: Our
      results indicate that the change in gross tumor volume for head-and-neck cancer
      can be adequately described by a relatively simple radiobiologic model. In future
      research, we propose to study the variation of model parameters by fitting to
      clinical data for a cohort of patients with head-and-neck cancer and other
      tumors. The potential impact of other processes, like concurrent chemotherapy, on
      tumor volume should be evaluated.

PMID- 19596174
TI  - Clinical utility of the modified segmental boost technique for treatment of the
      pelvis and inguinal nodes.
AB  - PURPOSE: Low-lying pelvic malignancies often require simultaneous radiation to
      pelvis and inguinal nodes. We previously reported improved homogeneity with the
      modified segmental boost technique (MSBT) compared to that with traditional
      methods, using phantom models. Here we report our institutional clinical
      experience with MSBT. METHODS AND MATERIALS: MSBT patients from May 2001 to March
      2007 were evaluated. Parameters analyzed included isocenter/multileaf collimation
      shifts, time per fraction (four fields), monitor units (MU)/fraction, femoral
      doses, maximal dose relative to body mass index, and inguinal node depth. In
      addition, a dosimetric comparison of the MSBT versus intensity modulated
      radiation therapy (IMRT) was conducted. RESULTS: Of the 37 MSBT patients
      identified, 32 were evaluable. Port film adjustments were required in 6% of
      films. Median values for each analyzed parameter were as follows: MU/fraction,
      298 (range, 226-348); delivery time, 4 minutes; inguinal depth, 4.5 cm; volume
      receiving 45 Gy (V45), 7%; V27.5, 87%; body mass index, 25 (range, 16.0-33.8).
      Inguinal dose was 100% in all cases; in-field inhomogeneity ranged from 111% to
      118%. IMRT resulted in significantly decreased dose to normal tissue but required
      more time for treatment planning and a higher number of MUs (1,184 vs. 313 MU).
      CONCLUSIONS: In our clinical experience, the mono-isocentric MSBT provides a high
      degree of accuracy, improved homogeneity compared with traditional techniques,
      ease of simulation, treatment planning, treatment delivery, and acceptable
      femoral doses for pelvic/inguinal radiation fields requiring 45 to 50.4 Gy. In
      addition, the MSBT delivers a relatively uniform dose distribution throughout the
      treatment volume, despite varying body habitus. Clinical scenarios for the use of
      MSBT vs. intensity-modulated radiation therapy are discussed. To our knowledge,
      this is the first study reporting the utility of MSBT in the clinical setting.

PMID- 19596175
TI  - Readability and comprehensibility of patient education material in hand-related
      web sites.
AB  - PURPOSE: As patients are more frequently referring to the Internet for
      information on their musculoskeletal problems, the readability and
      comprehensibility of these educational materials becomes increasingly more
      important to most of the lay public. In this study, we investigated the
      readability of the currently available web sites of the American Society for
      Surgery of the Hand (ASSH) and the American Academy of Orthopaedic Surgeons
      (AAOS) that pertain to hand and wrist problems, to assess their usefulness as a
      source for patient information. METHODS: We analyzed all articles available in
      2008 from the AAOS web site within the Patient Education Library under the
      heading, "Hand & Wrist" and from the ASSH web site under the heading, "Hand
      Conditions." A total of 83 articles were identified for hand conditions. Each
      article was analyzed by the Flesch-Kincaid program available in Microsoft Office
      Word software and the Dale-Chall grade-level assessor. These program models
      analyze all words in the specified text and return a grade level that corresponds
      to the difficulty level of the text. RESULTS: The AAOS web sites contained 34
      articles with a mean Flesch-Kincaid grade level of 8.5 and a mean Dale-Chall
      grade level of 8.8. The ASSH web site contained 49 articles showing a mean Flesch
      Kincaid grade level of 10.4 and a mean Dale-Chall grade level of 10.8.
      CONCLUSIONS: Our results suggest that the patient education materials found on
      the AAOS and ASSH web sites have readability scores that are higher than the
      recommended reading levels and thus may be too difficult to be understood by a
      substantial portion of the U.S. population.

PMID- 19596176
TI  - Invasive potential of human rheumatoid tenosynovial cells is in part MT1-MMP
      dependent.
AB  - PURPOSE: In rheumatoid arthritis, tenosynovial invasion of tendon is associated
      with an increased rate of tendon rupture and a worse clinical prognosis compared
      to noninvasive disease. Tendon is composed predominantly of type I collagen,
      which can be efficiently degraded by collagenolytic matrix metalloproteinases
      (MMPs), one of which, MT1-MMP, is membrane bound and inhibited by tissue
      inhibitor of metalloproteinase-2, but not by TIMP-1. The role of MT1-MMP in
      tendon disease is unknown. In this report, we investigate the potential role of
      MT1-MMP in invasion of tenosynovium into tendon. METHODS: Matched synovial
      specimens were obtained from different regions of the wrist in 36 rheumatoid
      patients having extensor tenosynovectomy in most instances. The tenosynovium that
      was removed was surrounding tendons (termed encapsulating) invading tendons
      (termed invasive), and wrist joint synovium. Samples of tenosynovium were tested
      for MT1-MMP using Western blotting, and the MT1-MMP activity was quantified using
      commercial assays. Next, a 3-dimensional collagen assay was created, using
      freshly isolated tenosynovium. Transwell collagen invasion assays were then
      performed, using isolated tenosynovial cells to determine MT1-MMP's effect on
      tendon invasion. RESULTS: The MT1-MMP was present in 9 of 10 joint samples, 4 of
      6 encapsulating tenosynovial samples, and 5 of 5 invasive tenosynovial samples.
      Activity assays demonstrated that mean levels of active MT1-MMP produced by joint
      samples was 6.1 +/- 4.1 ng/mL; by encapsulating tenosynovium was 3.9 +/- 4.2
      ng/mL, and by invasive tenosynovium was 6.2 +/- 1.1 ng/mL. The 3-dimensional gel
      assays demonstrated that cell invasion was reduced by the addition of TIMP-2 and
      GM-6001(a broad spectrum matrix metalloproteinase inhibitor) but not by TIMP-1.
      The addition of TIMP-2 to invasion assays reduced the mean number of cells that
      invaded the collagen membrane from 11 +/- 5 cells/field to 7 +/- 3 cells/field in
      treated samples (p = .04). CONCLUSIONS: Our results demonstrate that MT1-MMP is
      present in rheumatoid tenosynovium and that MT1-MMP facilitates tenosynovial cell
      invasion into a type I collagen matrix, suggesting that MT1-MMP plays a crucial
      role in tendon invasion. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

PMID- 19596177
TI  - Unilateral mydriasis due to hemorrhoidal ointment.
AB  - BACKGROUND: The finding of a unilaterally dilatated pupil in a patient who is
      otherwise alert and unimpaired can pose an interesting diagnostic problem.
      Algorithms have outlined the approach to evaluating anisocoria, but do not stress
      the importance of toxic exposures. CASE REPORT: A patient with a history of
      depression and chronic headaches was referred to the emergency department from an
      ophthalmologist's clinic with the findings of asymmetrically dilatated pupils and
      blurred vision. Detailed history revealed that for several weeks before the onset
      of symptoms, the patient applied to her eyelids hemorrhoidal ointment that
      contained an active ingredient known to produce mydriasis. CONCLUSION: In the
      absence of neurologic deficits, clinical history should search for a toxic or
      pharmacologic etiology of abnormal mydriasis. A detailed physical examination and
      bedside diagnostic maneuvers can help distinguish benign causes of an abnormally
      dilatated pupil from more serious causes relating to central nervous system
      lesions, potentially sparing the patient from unnecessary neuroimaging.

PMID- 19596178
TI  - Caustic injury due to unintentional ingestion of a cooking adjunct.

PMID- 19596179
TI  - Primary venous aneurysm of the internal iliac vein.

PMID- 19596180
TI  - Successful pain relief of cutaneous leiomyomata due to reed syndrome with the
      combination treatment of pregabalin and duloxetine.

PMID- 19596181
TI  - Development and validation of a prediction model with missing predictor data: a
      practical approach.
AB  - OBJECTIVE: To illustrate the sequence of steps needed to develop and validate a
      clinical prediction model, when missing predictor values have been multiply
      imputed. STUDY DESIGN AND SETTING: We used data from consecutive primary care
      patients suspected of deep venous thrombosis (DVT) to develop and validate a
      diagnostic model for the presence of DVT. Missing values were imputed 10 times
      with the MICE conditional imputation method. After the selection of predictors
      and transformations for continuous predictors according to three different
      methods, we estimated regression coefficients and performance measures. RESULTS:
      The three methods to select predictors and transformations of continuous
      predictors showed similar results. Rubin's rules could easily be applied to
      estimate regression coefficients and performance measures, once predictors and
      transformations were selected. CONCLUSION: We provide a practical approach for
      model development and validation with multiply imputed data.

PMID- 19596182
TI  - Vaccination with autoreactive CD4(+)Th1 clones in lupus-prone MRL/Mp-Fas(lpr/lpr)
      mice.
AB  - We studied the efficacy of T cell vaccination with CD4(+)alphabetaTh1 clones in
      lupus-prone MRL/Mp-Fas(lpr/lpr) (MRL/lpr) mice. CD4(+)alphabeta Th1 clones, dna51
      (Vbeta8.3) and rnp2 (Vbeta14), which stimulated anti-dsDNA or U1
      ribonucleoprotein (U1RNP) antibody (Ab) production respectively, were isolated
      from splenocytes of MRL/lpr mice. Antinuclear Ab kinetics, renal function, renal
      histology, survival rate, and lymphocyte subpopulations in the spleen were
      monitored after intravenous adoptive transfer of IL-2-stimulated (s-) or
      irradiated (i-) clones to 3 week-old female MRL/lpr mice. Anti-idiotypic humoral
      and T cell responses against the transferred autoreactive Th1 clones were
      determined in parallel. Compared with PBS-treated MRL/lpr mice, anti-dsDNA Ab
      titers, and the activity index for lupus nephritis were all decreased in MRL/lpr
      mice vaccinated with i-dna51 cells, whereas survival rate was not improved. The
      numbers of CD4(+)Vbeta8.3 T cells in the spleen were also significantly decreased
      in these mice. Anti-idiotypic Abs recognizing a 12 amino acid sequence of clone
      dna51 T cell receptor Vbeta8.3-complementarity-determining region (CDR) 3 were
      detected in the MRL/lpr mice that received i-dna51 or s-dna51 cells. These Abs
      suppressed dna51 cell proliferation, as well as cytotoxicity of CD8(+)T cells
      against dna51. The present study suggests that vaccination with
      CD4(+)alphabetaTh1 clone, dna51, elicits anti-idiotypic T cell and humoral
      responses against dna51 in MRL/lpr mice, although the immunoregulatory effects on
      lupus may be limited.

PMID- 19596183
TI  - Bcl-xL is required for the development of functional regulatory CD4 cells in
      lupus-afflicted mice following treatment with a tolerogenic peptide.
AB  - Dysregulated expression of Bcl-xL and Bcl-2 may initiate the development of
      autoimmune diseases including systemic lupus erythematosus (SLE). A tolerogenic
      peptide designated hCDR1 was shown to ameliorate manifestations of spontaneous
      and induced murine SLE. Recently, we demonstrated that Bcl-xL plays a critical
      role in the modulating effects of hCDR1, as manifested by reducing the state of
      activation of lymphocytes and by down-regulating the secretion of the pathogenic
      cytokines, IFN-gamma and IL-10. Here we studied the role of Bcl-xL in the
      development and function of CD4 regulatory T-cells (Treg) from hCDR1-treated, SLE
      afflicted (New-Zealand-Black x New-Zealand-White) F1 mice. We report that Bcl-xL
      was up-regulated in CD4 Treg of tolerized mice, where it played a role in
      inducing the regulatory/inhibitory molecules Foxp3, CTLA-4, and TGF-beta and in
      repressing PD-1. Further, Bcl-xL mediated the induction of CTLA-4 and TGF-beta in
      effector T cells (Teff) by CD4 Treg of the tolerized mice. The induction of Bcl
      xL in Teff by Treg was TGF-beta dependent and CTLA-4 independent, leading to
      inhibition of proliferation and to a decrease in activated Teff. We conclude that
      Bcl-xL is required for the development and function of CD4 Treg, which ameliorate
      lupus following treatment with a tolerogenic peptide.

PMID- 19596184
TI  - Discipline-specific insulin sensitivity in athletes.
AB  - OBJECTIVE: Weight status and abnormal liver function are the two factors that
      influence whole-body insulin sensitivity. The main goal of the study was to
      compare insulin sensitivity in athletes (n=757) and physically active controls
      (n=670) in relation to the two factors. METHODS: Homeostatic metabolic assessment
      for insulin resistance (HOMA-IR), weight status, and abnormal liver function
      (alanine aminotransferase and aspartate aminotransferase) were determined from 33
      sports disciplines under morning fasted condition. This study was initiated in
      autumn 2006 and repeated in autumn 2007 (n=1508) to ensure consistency of all
      observations. RESULTS: In general, HOMA-IR and blood pressure levels in athletes
      were significantly greater than those in physically active controls but varied
      widely with sport disciplines. Rowing and short-distance track athletes had
      significantly lower HOMA-IR values and archery and field-throwing athletes had
      significantly higher values than the control group. Intriguingly, athletes from
      22 sports disciplines displayed significantly greater body mass index values
      above control values. Multiple regression analysis showed that, for non-athlete
      controls, body mass index was the only factor that contributed to the variations
      in HOMA-IR. For athletes, body mass index and alanine aminotransferase
      independently contributed to the variation of HOMA-IR. CONCLUSION: This is the
      first report documenting HOMA-IR values in athletes from a broad range of sport
      disciplines. Weight status and abnormal liver function levels appear to be the
      major contributors predicting insulin sensitivity for the physically active
      population.

PMID- 19596185
TI  - Endotoxin level in ischemia-reperfusion injury in rats: effect of glutamine
      pretreatment on endotoxin levels and gut morphology.
AB  - OBJECTIVE: We aimed to investigate the effect of enteral glutamine (Gln)
      pretreatment on plasma endotoxin level and intestinal histopathologic changes
      during intestinal ischemia-reperfusion (I/R) injury in rats. METHODS: Intestinal
      I/R was induced by 60-min occlusion of the superior mesenteric artery followed by
      60 min of reperfusion. Animals were pretreated with Gln by orogastric route for
      different periods and doses. To investigate the effects of gut decontamination on
      intestinal I/R injury, animals were pretreated with neomycin sulfate and
      erythromycin phosphate by orogastric route. In another series, dl-alpha
      tocopherol hydrogen succinate was used to investigate the effects of vitamin E on
      intestinal I/R injury. Plasma endotoxin level was measured by the colorimetric
      "limulus amebocyte lysate" test. Intestinal mucosal injury was scored on a scale
      described by Chiu et al. (Archive in Surgery 1970;101:478-483). RESULTS:
      Intestinal I/R increased the plasma endotoxin level and worsened the
      histopathologic score significantly. Gln pretreatment (1g/kg) for 4 d reduced the
      I/R-induced elevation of plasma endotoxin level. However, a significant
      improvement in histopathologic score could only be achieved when the pretreatment
      was given for 7 d. Antibiotic pretreatment lowered plasma endotoxin level without
      affecting the I/R-induced histopathologic changes, whereas vitamin E pretreatment
      affected plasma endotoxin level and histopathologic changes. CONCLUSION: These
      results suggest a lack of association between plasma endotoxin level and
      intestinal histopathologic alterations in intestinal I/R.

PMID- 19596186
TI  - Gene-environment interactions and obesity--further aspects of genomewide
      association studies.
AB  - Advances in genotyping technologies have facilitated the advent of the genomewide
      association studies in large study populations and thereby led to the
      identification of an impressive-and still increasing-number of genetic variants
      with significant impact on the risk of widespread lifestyle health problems such
      as obesity, diabetes, and cardiovascular disease. Yet, the scientific community
      is a long way from reaching a comprehensive picture of the heritable components
      of these diseases and advancing from plain statistical significance into a
      biological understanding where the true contribution to a trait is recognized.
      Increasingly large study populations, denser single-nucleotide polymorphism
      mapping, deep sequencing, and raised awareness of the importance of structural
      variants may add to the known genetic variance underlying common complex
      disorders; however, genetic variance alone probably cannot account for disease
      susceptibility without the addition of pre- and postnatal environmental and/or
      behavioral factors. Moreover, an interaction between genetic and environmental
      factors may hinder the detection of genetic effects if not accounted for, e.g.,
      in genomewide association studies, and prospective cohort studies have hence been
      proposed to surpass the classic case-control design. With a focus on obesity we
      describe some of the recently reported gene-environment interactions for
      polymorphisms identified in the FTO and INSIG2 genes. Ultimately, a thorough
      understanding of the gene-environment interactions underlying a common complex
      condition such as obesity may suggest novel treatment or intervention strategies
      to complement the harmful effect of detrimental genetic variation and thus may
      assist in improving the quality of life for affected individuals.

PMID- 19596187
TI  - Metalloproteolytic balance in asthma: when and how could its regulation?

PMID- 19596188
TI  - Once-daily ciclesonide via metered-dose inhaler: Similar efficacy and safety with
      or without a spacer.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are recommended as first-line treatment
      for adults and children with persistent asthma. The Global Initiative for Asthma
      recommends that patients taking medium- or high-dose ICS delivered by metered
      dose inhalers (MDIs) should use a spacer device. METHODS: This randomized, open
      label, 12-week, non-inferiority study compared the efficacy and safety of
      ciclesonide 160microg once daily delivered via hydrofluoroalkane-MDI alone
      (CIC160) or with a spacer (either an AeroChamber Plus [CIC160P] or an AeroChamber
      MAX [CIC160M]) in patients with persistent asthma. The primary efficacy variable
      was change in forced expiratory volume in 1s (FEV(1)) from baseline to study end.
      RESULTS: Significant improvements in FEV(1) were observed from baseline to study
      end in each treatment group; least squares mean change from baseline ranged
      between 0.32 and 0.34L in the per-protocol (PP) analysis and similar results were
      observed for the intention-to-treat (ITT) analysis (p<0.0001 for all). Non
      inferiority of CIC160P and CIC160M to CIC160 was observed for both PP and ITT
      populations (p<0.0001 [one-sided]). In all groups, daily asthma symptom scores
      were reduced to 0 and significant reductions were observed in rescue medication
      use at study end (p<0.0001 versus baseline for all). Ciclesonide was well
      tolerated in all groups and no cases of oral candidiasis were reported. Morning
      serum cortisol levels significantly increased in all groups from baseline to
      study end (p< or =0.0389), with no significant between-treatment differences.
      CONCLUSION: In patients with persistent asthma, ciclesonide was shown to have
      similar efficacy and tolerability when administered via MDI alone or with a
      spacer.

PMID- 19596189
TI  - Assessment of the recycling potential of fresh concrete waste using a factorial
      design of experiments.
AB  - Recycling of industrial wastes and by-products can help reduce the cost of waste
      treatment prior to disposal and eventually preserve natural resources and energy.
      To assess the recycling potential of a given waste, it is important to select a
      tool capable of giving clear indications either way, with the least time and work
      consumption, as is the case of modelling the system properties using the results
      obtained from statistical design of experiments. In this work, the aggregate
      reclaimed from the mud that results from washout and cleaning operations of fresh
      concrete mixer trucks (fresh concrete waste, FCW) was recycled into new concrete
      with various water/cement ratios, as replacement of natural fine aggregates. A
      3(2) factorial design of experiments was used to model fresh concrete consistency
      index and hardened concrete water absorption and 7- and 28-day compressive
      strength, as functions of FCW content and water/cement ratio, and the resulting
      regression equations and contour plots were validated with confirmation
      experiments. The results showed that the fresh concrete workability worsened with
      the increase in FCW content but the water absorption (5-10 wt.%), 7-day
      compressive strength (26-36 MPa) and 28-day compressive strength (32-44 MPa)
      remained within the specified ranges, thus demonstrating that the aggregate
      reclaimed from FCW can be recycled into new concrete mixtures with lower natural
      aggregate content.

PMID- 19596190
TI  - Long-term outcome after polychemotherapy and intensive local radiation therapy of
      high-grade osteosarcoma.
AB  - BACKGROUND: Current standard therapy for high-grade osteosarcoma is neoadjuvant
      chemotherapy and complete resection of the primary tumour. Irradiation can
      improve local control if complete tumour resection is not possible or refused,
      but data on long-term outcome are not available. PATIENTS AND METHODS: We report
      on long-term results for overall survival, occurrence of local recurrence and
      metastasis, joint function and side-effects in 13 patients with high-grade
      osteosarcoma having been treated with a combination of local irradiation and
      polychemotherapy (median follow-up of 13.5 years). RESULTS: Ten of the 13
      patients were alive 4-23 years after diagnosis. Three patients suffered local
      recurrence, in 2 of them tumour control and long-term survival could be achieved
      by secondary salvage surgery and polychemotherapy. In 5 patients pathological
      fractures of the irradiated bones occurred, none of them was associated with
      local recurrence. In 7 of the 10 long-term survivors good or fair joint function
      was achieved. CONCLUSIONS: We conclude that combination of chemotherapy and
      intensive local irradiation can achieve long-term local control and even cure in
      high-grade osteosarcoma. Thus radiation therapy may represent an alternative to
      definite surgery in selected patients, in particular in those with good response
      to chemotherapy, when surgery is not feasible or refused.

PMID- 19596191
TI  - Targeted therapies in the treatment of advanced/metastatic NSCLC.
AB  - The treatment of advanced non-small cell lung cancer (NSCLC) has evolved
      substantially during the last years. Chemotherapy remains the cornerstone of
      treatment and prolongs survival with a positive impact on quality of life.
      However, we seem to have reached a plateau of activity in the treatment of NSCLC.
      Recently, the addition of bevacizumab or cetuximab to chemotherapy doublets has
      improved the outcome in selected patients with advanced NSCLC. Furthermore, the
      use of erlotinib and gefitinib is an alternative for second line treatment.
      Advances in our understanding of molecular biology of cancer and mechanisms of
      tumourigenesis have further enabled the discovery of several potential molecular
      targets and development of novel 'targeted therapies'. The purpose of this study
      is to review current data on the role of targeted therapies in the treatment of
      advanced NSCLC.

PMID- 19596192
TI  - Integrated Constructed Wetlands (ICW) for livestock wastewater management.
AB  - Social, economic and environmental coherence is sought in the management of
      livestock wastewater. Wetlands facilitate the biogeochemical processes that
      exploit livestock wastewater and provide opportunities to achieve such coherence
      and also to deliver on a range of ecosystem services. The Integrated Constructed
      Wetland (ICW) concept integrates three inextricably linked objectives: water
      quantity and quality management, landscape-fit to improve aesthetic site values
      and enhanced biodiversity. The synergies derived from this explicit integration
      allow one of the key challenges for livestock management to be addressed. An
      example utilizing twelve ICW systems from a catchment on the south coast of
      Ireland demonstrates that over an eight year period mean reduction of total and
      soluble phosphorus (molybdate reactive phosphorus) exceeded 95% and the mean
      removal of ammonium-N exceeded 98%. This paper reviews evidence regarding the
      capacity of ICWs to provide a coherent and sustainable alternative to
      conventional systems.

PMID- 19596193
TI  - Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide
      Y Y1 receptor antagonists.
AB  - A novel series of cyclohexanamine derivatives was designed and synthesized as
      potent and selective human neuropeptide Y Y1 receptor antagonists. Modification
      of high-throughput screening hit compound 1 resulted in the identification of
      compound 3i, which displays potent Y1 activity and good selectivity towards hERG
      K(+) channel and serotonin transporter.

PMID- 19596194
TI  - Tetrahydropyridine derivatives with inhibitory activity on the production of
      proinflammatory cytokines: part 1.
AB  - We investigated proinflammatory cytokine TNFalpha production inhibitors in order
      to develop novel anti-inflammatory agents. According to the results, we found
      that 17, a pyrrole derivative possessing a tetrahydropyridine group at the beta
      position, showed potent inhibitory activity in vitro (inhibition of
      lipopolysaccharide (LPS) induced TNFalpha production in human whole blood,
      IC(50)=1.86 microM) and in vivo (inhibition of LPS induced TNFalpha production in
      mice, ID(50)=5.98 mg/kg).

PMID- 19596195
TI  - Potent aza-peptide derived inhibitors of HCV NS3 protease.
AB  - Chronic hepatitis C infection is the primary cause for cirrhosis of the liver and
      hepatocellular carcinoma leading to liver failure and transplantation. The
      etiological agent hepatitis C virus produces a single positive strand RNA that is
      processed further with the help of NS3 serine protease to produce mature virus.
      Inhibition of this protease can potentially be used to develop drugs for HCV
      infections. Boceprevir is a ketoamide derived novel inhibitor of HCV NS3 protease
      that has been progressed to clinical trials and proven to be efficacious in
      humans. Herein, we report our efforts in identifying an aza-peptide derivative as
      a potential second generation compound, that lacks electrophilic ketoamide group
      and are potent in enzyme and replicon assay.

PMID- 19596196
TI  - Glycolipid ester-type heterodimers from Ipomoea tyrianthina and their
      pharmacological activity.
AB  - Tyrianthins A (1) and B (2), two new partially acylated glycolipid ester-type
      heterodimers were isolated from Ipomoea tyrianthina. Scammonic acid A was
      determined as the glycosidic acid in both monomeric units. Tyrianthin A (1)
      (IC(50) 0.24+/-0.09 microM and E(max) 81.80+/-0.98%), and tyrianthin B (2)
      (IC(50) 0.14+/-0.08 microM and E(max) 87.68+/-0.72%) showed significant in vitro
      relaxant effect on aortic rat rings, in endothelium- and concentration-dependent
      manners. Also, these compounds were able to increase the release of GABA and
      glutamic acid in brain cortex, and displayed weak antimycobacterial activity.

PMID- 19596197
TI  - Identification of potential cellular targets of aloisine A by affinity
      chromatography.
AB  - Affinity chromatography was used to identify potential cellular targets of
      aloisine A (7-n-butyl-6-(4'-hydroxyphenyl)-5H-pyrrolo[2,3b]pyrazine), a potent
      inhibitor of cyclin-dependent kinases. This technique is based on the
      immobilization of the drug on a solid matrix, followed by identification of
      specifically bound proteins. To this end, both aloisine A and the protein-kinase
      inactive control N-methyl aloisine, bearing extended linker chains have been
      synthesized. We present the preparation of such analogues having the triethylene
      glycol chain at different positions of the molecule, as well as their
      immobilization on an agarose-based matrix. Affinity chromatography of various
      biological extracts on the aloisine matrices allowed the identification of both
      protein kinases and non-kinase proteins as potential cellular targets of
      aloisine.

PMID- 19596198
TI  - Design and synthesis of new 1,3-benzthiazinan-4-one derivatives as selective
      cyclooxygenase (COX-2) inhibitors.
AB  - A new group of 1, 3-benthiazinan-4-ones, possessing a methyl sulfonyl
      pharmacophore, were synthesized and their biological activities were evaluated
      for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition
      studies identified 3-(p-fluoropheny)-2-(4-methylsulfonylphenyl)-1,3-benzthiazinan
      4-one (7b) as a potent (IC(50)=0.05 microM) and selective (selectivity index=259)
      COX-2 inhibitor.

PMID- 19596199
TI  - Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside
      disulfide mimics of nicotinamide adenine dinucleotide analogues.
AB  - Diadenosine disulfide (5) was reported to inhibit NAD kinase from Listeria
      monocytogenes and the crystal structure of the enzyme-inhibitor complex has been
      solved. We have synthesized tiazofurin adenosine disulfide (4) and the disulfide
      5, and found that these compounds were moderate inhibitors of human NAD kinase
      (IC(50)=110 microM and IC(50)=87 microM, respectively) and Mycobacterium
      tuberculosis NAD kinase (IC(50)=80 microM and IC(50)=45 microM, respectively). We
      also found that NAD mimics with a short disulfide (-S-S-) moiety were able to
      bind in the folded (compact) conformation but not in the common extended
      conformation, which requires the presence of a longer pyrophosphate (-O-P-O-P-O-)
      linkage. Since majority of NAD-dependent enzymes bind NAD in the extended
      conformation, selective inhibition of NAD kinases by disulfide analogues has been
      observed. Introduction of bromine at the C8 of the adenine ring restricted the
      adenosine moiety of diadenosine disulfides to the syn conformation making it even
      more compact. The 8-bromoadenosine adenosine disulfide (14) and its di(8
      bromoadenosine) analogue (15) were found to be the most potent inhibitors of
      human (IC(50)=6 microM) and mycobacterium NAD kinase (IC(50)=14-19 microM
      reported so far. None of the disulfide analogues showed inhibition of lactate-,
      and inosine monophosphate-dehydrogenase (IMPDH), enzymes that bind NAD in the
      extended conformation.

PMID- 19596200
TI  - Inhibitory effects of flavonoids isolated from Fragaria ananassa Duch on IgE
      mediated degranulation in rat basophilic leukemia RBL-2H3.
AB  - We isolated the 4 kinds of flavonoids from strawberry 'Nohime' and examined the
      effect of these flavonoids on the degranulation in RBL-2H3 cells. The flavonoids
      were found to suppress the degranulation from Ag-stimulated RBL-2H3 cells to
      different extents. To disclose the inhibitory mechanism of degranulation by
      flavonoids, we examined their effects on the intracellular free Ca(2+)
      concentration ([Ca(2+)]i) and the intracellular signaling pathway such as Lyn,
      Syk, and PLCgammas. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was
      elevated by Fc epsilonRI activation, but these flavonoid treatments reduced the
      elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Kaempferol strongly
      suppressed the activation of Syk and PLCgammas. It was thus suggested that
      suppression of Ag-stimulated degranulation by the flavonoids is mainly due to
      suppression of [Ca(2+)]i elevation and Syk activation. These results suggested
      that strawberry would be of some ameliorative benefit for the allergic symptoms.

PMID- 19596202
TI  - Applicability of the polyphenylene oxide film dosimeter to high UV exposures in
      aquatic environments.
AB  - Previous research has proven that the Poly (2,6-dimethyl-1, 4-phenylene oxide)
      (PPO) dosimeter is capable of receiving both in-air and underwater UV exposures
      that are significantly greater than those of the more commonly used polysulphone
      dosimeter, within a range of accuracy close to what would be expected of
      dosimetric measurements made in-air provided that the necessary calibrations are
      completed correctly by factoring in different atmospheric column ozone levels,
      SZA ranges, varying water turbidity and DOM levels. However, there is yet to be
      an investigation detailing the performance of the PPO dosimeter and its ability
      to measure UV in an actual field environment over an extended period of time.
      This research aims to bridge this gap in the knowledge by presenting a
      measurement campaign carried out in two real world aquatic environments and a
      simulated sea water environment using a batch of PPO dosimeters set at different
      depths and aligned to a range of different angles and geographical directions by
      means of attachment to a custom built dosimeter submersible float (DSF) unit over
      the space of a year at a sub-tropical location. Results obtained from this
      measurement campaign were used to compute a K(d) value for the sea water in each
      particular season. These K(d) values where found to be in close agreement to
      standalone K(d) values derived from results taken using a standard calibrated
      spectrometer in the same sea water.

PMID- 19596201
TI  - p-Guanidinoethyl calixarene and parent phenol derivatives exhibiting
      antibacterial activities. Synthesis and biological evaluation.
AB  - The tetra-para-guanidinoethyl-calix[4]arene, its distally-disubstituted ether
      derivatives involving 2,2'-bithiazolyl- or 2,2'-bipyridyl-methyl groups, as well
      as the para-guanidinoethylphenol and its analogous derivatives have been
      synthesized, fully characterized and evaluated as antibacterial agents towards
      both gram positive and gram negative reference bacteria. The simple phenolic
      species showed lower activity than their calixarene analogues, confirming the
      hypothesis that a synergistic effect should result from the spatial organization
      of guanidinium and heterocycles on a macrocyclic scaffold. Introduction of the
      bithiazole and bipyridine substituents enhanced the activity of simple phenol
      derivatives, reaching, for the two Staphylococcus aureus strains in particular,
      the values obtained for their calixarenic parents. MTT viability assays were
      carried out to determine selectivity indexes.

PMID- 19596203
TI  - Employment status, coronary heart disease, and stroke among women.
AB  - PURPOSE: To investigate the association of employment status with coronary heart
      disease (CHD) and ischemic stroke among middle-aged women. METHODS: Proportional
      hazards regression was used to assess the association of employment status,
      incident CHD, and incident ischemic stroke among 7,058 women, ages 45-64 years at
      baseline (1987-1989), from the Atherosclerosis Risk in Communities Study.
      RESULTS: After adjusting for age and race-field center, women employed outside
      the home had a decreased risk of CHD (hazard ratio [HR], 0.70; 95% confidence
      interval [95% CI], 0.56-0.86) and ischemic stroke (HR, 0.62; 95% CI, 0.47-0.84)
      compared with homemakers. Differences in cardiovascular disease risk factors
      partially accounted for the association of employment status and CHD (HR, 0.79;
      95% CI, 0.63-0.99) and stroke (HR, 0.79; 95% CI, 0.58-1.08). Also, modest
      differences were noted when the results were stratified by education, with
      employed women having a lower risk of CHD (HR, 0.65; 95% CI, 0.45-0.93) than
      homemakers among those with less than a high school education. CONCLUSIONS: Women
      employed outside of the home had a lower risk of CHD and stroke compared with
      homemakers and, for CHD, this association was stronger among women with less than
      a high school education. These findings suggest additional research into the
      varied occupational experiences of women, socioeconomic status, and health is
      warranted.

PMID- 19596204
TI  - Waist-hip-ratio as a predictor of all-cause mortality in high-functioning older
      adults.
AB  - PURPOSE: The relationship between obesity and mortality in older adults is
      debated, with concern that body mass index (BMI) may be an imperfect measure of
      obesity in this age group. We assessed the relationship between three measures of
      obesity and all-cause mortality in a group of healthy older adults. METHODS: We
      analyzed data from the MacArthur Successful Aging Study, a longitudinal study of
      high-functioning men and women, ages 70-79 years at baseline. We examined 12
      year, all-cause mortality risk by BMI, waist circumference, and waist-to-hip
      circumference ratio (WHR). Proportional hazards regression was used to adjust for
      gender, race, baseline age, and smoking status. We tested for obesity
      interactions with gender, race, and smoking status and conducted stratified
      analyses based on the results of interaction testing. RESULTS: There was no
      association between all-cause mortality and BMI or waist circumference in either
      unadjusted or adjusted analyses. In contrast, all-cause mortality increased with
      WHR. There was an interaction with sex, so that there was a graded relationship
      between WHR and mortality in women (relative hazard, 1.28 per 0.1 increase in
      WHR; 95% confidence interval, 1.05-1.55) and a threshold relationship in men
      (relative hazard 1.75 for WHR>1.0 compared to WHR< or =1.0; 95% confidence
      interval, 1.06-2.91). CONCLUSION: WHR rather than BMI appears to be the more
      appropriate yardstick for risk stratification of high-functioning older adults.

PMID- 19596205
TI  - Heterogeneity in hepatitis B virus (HBV) seroprevalence estimates from U.S. adult
      incarcerated populations.

PMID- 19596206
TI  - Self-reported health symptoms and conditions among complementary and alternative
      medicine users in a large military cohort.
AB  - PURPOSE: To describe medical symptom and condition reporting in relation to
      complementary and alternative medicine (CAM) use among members of the US
      military. METHODS: CAM was defined as health treatments not widely taught at US
      medical schools or typically available at US hospitals. By using data from the
      Millennium Cohort Study, we included participants who completed a survey from
      2004 to 2006 (n=86,131) as part of this cross-sectional analysis in which we
      sought to identify demographic characteristics and types of health-related
      symptoms and conditions associated with CAM use. Chi-square tests were used to
      compare health assessed by self-reported symptoms and conditions among those not
      reporting CAM use with those reporting practitioner-assisted or self-administered
      CAM. RESULTS: Of 86,131 participants, 30% reported using at least one
      practitioner-assisted CAM therapy, 27% reported using at least one self
      administered CAM therapy, whereas 59% did not report using any CAM therapy. Both
      women and men who used CAM reported a greater proportion of specific health
      conditions and health-related symptoms compared with those not reporting CAM use
      (p<0.05). CONCLUSIONS: These findings illustrate that a relatively young adult
      occupational cohort of military personnel using CAM therapies also report
      multiple comorbidities which may indicate chronic illness management and poorer
      overall health.

PMID- 19596207
TI  - Point of care salivary diagnostics for systemic disease screening: if someone
      builds it, will dentistry come?

PMID- 19596208
TI  - Oral manifestations of primary immune deficiencies in children.
AB  - An important task for both dentists and pediatricians dealing with patients
      manifesting different oral lesions is to be able to differentiate changes
      signaling systemic disease from those appearing without any concomitant serious
      health problem. In this article, symptomatology of selected primary immune
      deficiency diseases are discussed with particular emphasis on oral manifestations
      reported in this group of disorders. Facial, dental, and oral findings compose a
      constellation of symptoms observed in immunodeficiency diseases. Predisposition
      to bacterial invasion, cytokine dysregulation, tissue inflammatory process, and
      necrosis lead to early-onset oral lesions and periodontitis. Developmental
      abnormalities, periodontal disease, and oral lesions may accompany
      immunodeficiency and require particular awareness directed toward diagnosis of an
      underlying disease of the immune system.

PMID- 19596209
TI  - Atypical non-progressive pneumonia in goats.
AB  - An outbreak of severe respiratory disease in a goat herd was associated with
      Mycoplasma ovipneumoniae, Mycoplasma arginini, Mannheimia haemolytica and
      Pasteurella multocida with mortality rates exceeding 20% in kids. Post mortem
      features in affected kids included severe pleuropneumonia, lung consolidation,
      large quantities of pleural fluid and pericarditis. This is the first report of
      atypical proliferative pneumonia in goats in Portugal.

PMID- 19596211
TI  - Selective detection of ordered sodium signals by a jump-and-return pulse
      sequence.
AB  - A simple pulse sequence, derived from the shaped pulse optimally exciting the
      central transition of a spin 3/2, can be used to selectively detect ordered
      sodium with a given quadrupolar coupling. The pulse sequence consists of two
      pulses with opposite phases and separated by a delay, called a quadrupolar jump
      and-return (QJR) sequence. This QJR sequence is tested with a phantom made of
      sodium ions in bacteriophage and in aqueous solution and its feasibility for
      contrast modification based on the quadrupolar coupling is demonstrated.

PMID- 19596210
TI  - Spinal cord long-term potentiation (LTP) is associated with increased dorsal horn
      gene expression of IL-1beta, GDNF and iNOS.
AB  - Previous data show that spinal cord long-term potentiation (LTP) can be induced
      by electrical high-frequency stimulation (HFS) conditioning applied to the
      sciatic nerve. It has been suggested that the cellular events leading to this
      form of plasticity may contribute to central hyperalgesia. In the present study,
      extracellular recordings from single dorsal horn neurons and quantitative real
      time reverse-transcriptase polymerase chain reaction (RT-PCR) on rat dorsal horn
      tissue were used to examine whether maintenance of spinal LTP is associated with
      changes in gene expression of the proinflammatory interleukin-1beta (IL-1beta),
      glial cell-line derived neurotrophic factor (GDNF), inducible nitric oxide
      synthase (iNOS), p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase
      2 (COX2) and tumor necrosis factor alpha (TNFalpha). The data demonstrated that
      the HFS conditioning induced a robust increase in the dorsal horn C-fibre
      responses, which outlasted the duration of the experiments of 6h (p<0.05, HFS vs.
      control). Moreover, a significant increase in the expression of mRNA for IL
      1beta, GDNF and iNOS were observed 6h following the HFS conditioning (p<0.05, HFS
      vs. control). For the first time we show that spinal cord LTP is associated with
      an increased dorsal horn expression of the genes for IL-1beta, GDNF and iNOS.

PMID- 19596212
TI  - Changes in health-related quality of life may predict recurrent breast cancer.
AB  - BACKGROUND: Patient-reported outcomes incorporated in cancer clinical trials, are
      increasingly hypothesized to be predictors of disease-free survival. Previous
      research supports health-related quality of life (HRQoL) as an independent
      predictor of survival in patients with advanced or metastatic breast cancer. In
      contrast, recent studies provide evidence that baseline HRQoL scores are not
      associated with increased risk of relapse or survival in women with early-stage
      breast cancer. One plausible assumption might be that baseline HRQoL scores are
      limited as predictors of a recurrence of breast cancer several years after the
      initial diagnosis. In this explorative study, we examined whether changes in
      HRQoL over time may predict breast cancer recurrence. As a supplement, we
      investigated whether baseline HRQoL predicted recurrence. METHODS: The study
      sample consisted of 141 participants in the International Breast Cancer Study
      Group adjuvant Trial 12-93 and Trial 14-93, from the Western region of Sweden.
      HRQoL was assessed, during a 5-year follow up. Poisson regression analysis was
      used to estimate the hazard function of recurrence depending on time since
      primary diagnosis and on HRQoL variables. RESULTS: According to the Poisson
      multivariable regression analysis changes in physical well-being (beta=0.00439, p
      value=0.0470), and nausea/vomiting (beta=-0.00612, p-value=0.0136) significantly
      predicted recurrence. Baseline HRQoL outcomes were not predictors of recurrence.
      CONCLUSIONS: Changes of HRQoL during adjuvant therapy may be associated with
      recurrence. This explorative finding needs prospective investigation.

PMID- 19596213
TI  - Learning packets in nursing education: reviving the past.
AB  - Learning packets gained popularity in nursing education in the 1960's. Recently,
      they have been cited as strategies for distance learning. The aim of this project
      was to integrate Topic Focused Learning Packets as a complementary teaching
      strategy for presentation of new content to large classes of undergraduate
      nursing students. In addition to reducing in-class content presentation time,
      goals included: fostering critical thinking, actively engaging the student, and
      providing opportunities for team-based interaction. Rationale, design process and
      packets will be described. The learning packet was viewed positively by the
      students and faculty. Among 134 students, 119 strongly agreed or agreed that the
      learning packet was effective in increasing their understanding of the content
      and achieving the course objectives.

PMID- 19596214
TI  - A Cochrane review of patient education for neck pain.
AB  - BACKGROUND CONTEXT: Neck pain is common, disabling, and costly. The effectiveness
      of patient education strategies is unclear. PURPOSE: To assess whether patient
      education strategies are of benefit for pain, function/disability, global
      perceived effect, quality of life, or patient satisfaction, in adults with neck
      pain with or without radiculopathy. STUDY DESIGN: Cochrane systematic review.
      METHODS: Computerized bibliographic databases were searched from their start to
      May 31, 2008. Eligible studies were randomized trials investigating the
      effectiveness of patient education strategies for neck pain. Paired independent
      reviewers carried out study selection, data abstraction, and methodological
      quality assessment. Relative risk and standardized mean differences were
      calculated. Because of differences in intervention type or disorder, no studies
      were considered appropriate to pool. RESULTS: Of the 10 selected trials, two
      (20%) were rated as of high quality. Patient education was assessed as follows:
      1) eight trials of advice focusing on activation compared with no treatment, or
      to various active treatments, including therapeutic exercise, manual therapy, and
      cognitive behavioral therapy, showed either inferiority or no difference for
      pain, spanning a full range of follow-up periods, acuity and disorder types. When
      compared with rest, two trials that assessed acute whiplash-associated disorder
      showed moderate evidence of no difference for advice focusing on activation; 2)
      two trials studying advice focusing on pain and stress coping skills found
      moderate evidence of no benefit for chronic neck pain at intermediate- to long
      term follow-up; and 3) one trial compared the effects of neck school to no
      treatment, yielding limited evidence of no benefit for pain, at intermediate-term
      follow-up in mixed acute/subacute/chronic neck pain. CONCLUSIONS: This review has
      not shown effectiveness for educational interventions for neck pain of various
      acuity stages and disorder types and at various follow-up periods, including
      advice to activate, advice on stress coping skills, and neck school. In future
      research, further attention to methodological quality is necessary. Studies of
      multimodal interventions should consider study designs, such as factorial
      designs, that permit discrimination of specific educational components.

PMID- 19596215
TI  - Populations for CRT devices.

PMID- 19596216
TI  - Perivascular epithelioid cell neoplasms: a systematic review of prognostic
      factors.
AB  - Perivascular epithelioid cell tumors (PEComas) are rare, soft tissue tumors
      characterized by epithelioid cells with clear or eosinophilic cytoplasm and a
      perivascular disbursement. We compiled the treatment and follow-up results from
      an extensive collection of reported gynecologic PEComa cases and statistically
      analyzed their respective therapy modalities and corresponding patient outcomes.
      In the group of patients with PEComa who received surgical management alone,
      there was a tendency for them to exhibit a lower disease recurrence rate.
      Conversely, patients with PEComa who initially received surgery and chemotherapy
      or radiation therapy were associated with a higher disease recurrence rate (P
      =.024). Metastatic involvement was related to higher patient mortality rates (P
      =.0001), although this finding was unrelated to treatment type. Surgical
      management alone may suffice for nonaggressive lesions, but chemotherapy and
      radiotherapy appear necessary for patients who present with high-risk histologic
      condition or metastatic disease. Because PEComas exhibit varying biologic
      behavior and an ill-defined presentation, the treatment for these lesions
      necessitates further evaluation.

PMID- 19596217
TI  - Comparison of a new reusable gynecologic laparoscopic electric morcellator with a
      disposable morcellator: a preliminary trial.
AB  - We compared the efficiency and safety of a newly developed reusable morcellator
      (Olympus VarioCarve) with that of a disposable morcellator (GyneCare Morcellex)
      for gynecologic laparoscopic surgery. In group 1 (n=15 patients; 11 myomectomies
      and 4 supracervical hysterectomies), the laparoscopic disposable morcellator was
      used, and in group 2 (n=14; 11 myomectomies and 3 supracervical hysterectomies),
      the reusable morcellator was used. There were no statistical differences in total
      tissue weight. Morcellating time was significantly shorter in group 2, and the
      rate of morcellation was significantly greater in group 2. Significantly fewer
      and longer pieces of tissue were removed with the reusable morcellator. No
      iatrogenic organ damage was observed.

PMID- 19596218
TI  - Fetal thoracic and bladder shunts.
AB  - Congenital obstructive lesions involving the bladder and the lung can lead to
      serious complications for the newborn. The in-utero placement of a diverting
      shunt in the fetal bladder or thoracic cavity can decrease the morbidity and
      mortality associated with these obstructive conditions. This review focuses on
      the indications for prenatal evaluation, technique, and outcomes for those
      fetuses with a lower urinary tract obstruction, congenital pleural effusion or
      macrocystic congenital cystic adenomatoid malformation after placement of a
      vesicoamniotic or thoracoamniotic shunt.

PMID- 19596220
TI  - Long-term outcomes of repeat vs initial trabeculectomy in open-angle glaucoma.
AB  - PURPOSE: To evaluate the long-term intraocular pressure (IOP) control and to
      identify risk factors for failure of repeat trabeculectomy with mitomycin C (MMC)
      in patients with open-angle glaucoma. DESIGN: Retrospective case-control study.
      METHODS: Seventy-five eyes (67 patients) that had undergone repeat trabeculectomy
      with MMC were matched to 75 eyes (64 patients) that had undergone initial
      trabeculectomy with MMC according to age, gender, race, diagnosis, preoperative
      IOP, number of glaucoma medications, and lens status in an institutional setting.
      Surgical successes were defined as: 1) IOP < or =18 mm Hg and > or = 20%
      reduction in IOP, 2) < or = 15 mm Hg IOP and > or = 25% reduction in IOP, and 3)
      < or = 12 mm Hg IOP and > or = 30% reduction in IOP from baseline, with or
      without glaucoma medications, and were assessed by Kaplan-Meier survival
      analyses. Risk factors for failure in the repeat trabeculectomy group were
      analyzed by the Cox proportional hazard regression model. The main outcome
      measures were success rate, number of medications, and visual acuity. RESULTS:
      Eyes that underwent initial trabeculectomy with MMC had a statistically
      significantly higher cumulative surgical success rate than those that underwent
      repeat trabeculectomy with MMC at 3 years according to criteria B (61.3% vs
      41.3%; P = .022) and C (52.0% vs 32.0%; P = .021). In eyes that underwent repeat
      trabeculectomy, younger age and requirement of laser suture lysis were
      significant risk factors for surgical failure. Eyes that underwent initial
      trabeculectomy required a statistically fewer number of medications than eyes
      that underwent repeat trabeculectomy (0.6 vs 1.2; P = .013). CONCLUSIONS: Repeat
      trabeculectomy with MMC is less successful at achieving IOP reduction in open
      angle glaucoma than is initial trabeculectomy with MMC at 3 years or more.

PMID- 19596219
TI  - Cocooning infants: Tdap immunization for new parents in the pediatric office.
AB  - OBJECTIVE: Vaccination with tetanus toxoid, reduced diphtheria toxoid, and
      acellular pertussis (Tdap) is recommended for adults who have close contact with
      infants aged <12 months to protect young infants from infection due to Bordetella
      pertussis. This study assessed the acceptance of Tdap vaccination among parents
      bringing their newborn to a pediatric office during the first month of life.
      METHODS: Parents of all newborns were consecutively approached for participation
      by a study coordinator who provided written information about the study and a
      Tdap vaccine information sheet. After obtaining informed consent, a study
      coordinator reviewed contraindications for Tdap vaccination. Tdap vaccine was
      given by a clinic nurse, but parents with a history of ever receiving Tdap
      vaccine or of receiving a tetanus and diphtheria vaccine (Td) within the previous
      2 years were excluded. RESULTS: Two hundred parents were approached for study
      participation, of whom 40 (20%) were ineligible to receive Tdap vaccine primarily
      due to receipt of Td vaccine within the previous 2 years (32/40). Of the 160
      eligible to receive Tdap vaccine, 82 (51.2%) received a dose. Although nearly 60%
      of vaccinated parents received Tdap vaccine the first time they were approached,
      over 40% received Tdap vaccine at a subsequent office visit occurring during the
      baby's first month of life. CONCLUSIONS: Offering Tdap vaccine in the pediatric
      office increases access to vaccination for both new fathers and mothers. When
      hospital-based, postpartum Tdap vaccination is not a routine practice, office
      based vaccination of parents offers an option for protecting young infants.

PMID- 19596221
TI  - [Postoperative complications in total thyroidectomy for Graves disease:
      comparison with multinodular benign goiter surgery].
AB  - OBJECTIVES: To study and compare postoperative complications of total
      thyroidectomy for Graves disease and multinodular benign goiters. MATERIAL AND
      METHODS: A retrospective study on 176 patients (37 with Graves disease and 139
      with multinodular benign goiters) over a period of 41 months was conducted.
      Postoperative calcemia and laryngeal palsy as well as hemorrhagic and infectious
      complications were studied and statistically compared using the Kruskal-Wallis
      test. RESULTS: There was no statistical difference concerning the occurrence of
      postoperative laryngeal palsy, hypoparathyroidism or hemorrhagic complications
      between these two groups of patients. Only a more frequent immediate
      postoperative hypocalcemia (day 1) in the Graves disease group was found.
      CONCLUSION: Total thyroidectomy in the surgical management of Graves disease,
      after a cautious medical preoperative preparation, appears to be a safe
      technique. Total thyroidectomy must be performed instead of subtotal
      thyroidectomy in order to avoid recurrences.

PMID- 19596222
TI  - 9th International Symposium on Avian Endocrinology.

PMID- 19596224
TI  - Thrombosis Research: Introduction of e-pages.

PMID- 19596225
TI  - Variations on the SnCl4 and CF3CO2Ag-promoted glycosidation of sugar acetates: a
      direct, versatile and apparently simple method with either alpha or beta
      stereocontrol.
AB  - Glycosidation of sugar peracetates (D-gluco, D-galacto) with SnCl(4) and
      CF(3)CO(2)Ag led to either 1,2-cis-, or 1,2-trans-glycosides, depending primarily
      on the alcohols used. In particular, 1,2-trans-glycosides, expected from acyl
      protected glycosyl donors, were formed in high yields with alcohols sharing
      specific features such as bulkiness, presence of electron-withdrawing groups or
      polyethoxy motifs. In contrast, simple alcohols afforded approximately 1:1
      mixtures of 2,3,4,6-tetra-O-acetyl, and 3,4,6-tri-O-acetyl 1,2-cis-glycosides due
      to anomerization and/or acid-catalyzed fragmentation of 1,2-orthoester
      intermediates. After reacetylation or deacetylation, acetylated or fully
      deprotected 1,2-cis-glycosides (alpha-D-gluco, alpha-D-galacto) were obtained in
      approximately 90% yields by a simple and direct method.

PMID- 19596226
TI  - Glucosylation of raffinose via alternansucrase acceptor reactions.
AB  - The glucansucrase known as alternansucrase [EC 2.4.1.140] can transfer glucosyl
      units from sucrose to raffinose to give good yields of oligosaccharides, which
      may serve as prebiotics. The main products were the tetrasaccharides alpha-d-Glcp
      (1-->3)-alpha-d-Galp-(1-->6)-alpha-d-Glcp-(1<-->2)-beta-d-Fruf and alpha-d-Glcp
      (1-->4)-alpha-d-Galp-(1-->6)-alpha-d-Glcp-(1<-->2)-beta-d-Fruf in ratios ranging
      from 4:1 to 9:1, along with lesser amounts of alpha-d-Glcp-(1-->6)-alpha-d-Galp
      (1-->6)-alpha-d-Glcp-(1<-->2)-beta-d-Fruf. Ten unusual pentasaccharide structures
      were isolated. Three of these arose from glucosylation of the major
      tetrasaccharide product, two each from the minor tetrasaccharides, and three were
      the result of glucosylations of the fructose acceptor product leucrose or
      isomaltulose. The major pentasaccharide product arose from glucosylation of the
      major tetrasaccharide at position 4 of the fructofuranosyl unit, to give a
      subunit structure analogous to that of maltulose. A number of hexasaccharides and
      higher oligosaccharides were also produced. Unlike alternansucrase,
      dextransucrase [EC 2.4.1.5] gave only a single tetrasaccharide product in low
      yield, and no significant amounts of higher oligosaccharides. The tetrasaccharide
      structure from dextransucrase was found to be alpha-d-Glcp-(1-->4)-alpha-d-Galp
      (1-->6)-alpha-d-Glcp-(1<-->2)-beta-d-Fruf, which is at odds with the previously
      published structure.

PMID- 19596223
TI  - Shame as a prospective predictor of self-inflicted injury in borderline
      personality disorder: a multi-modal analysis.
AB  - The primary aim of this study was to examine the prospective association of shame
      with self-inflicted injury (SII), including suicide attempts and nonsuicidal self
      injury, among women with borderline personality disorder (BPD) who were enrolled
      in a clinical trial (N = 77). A multi-method approach was used to assess self
      reported shame, nonverbal shame behaviors, and assessor ratings of shame during
      an interview regarding antecedents for a recent episode of SII. Higher levels of
      nonverbal shame behaviors predicted a higher likelihood of subsequent SII, and
      shorter time to SII, after controlling for past SII as well as other emotions
      associated with SII. Self-reported state shame and assessor ratings of shame were
      associated with prospective SII, but not after controlling for other emotions.
      These findings underscore the important role of shame in SII, particularly shame
      in the presence of contextual prompts for events that surround episodes of SII.

PMID- 19596227
TI  - Driving biofuels from field to fuel tank.
AB  - Rising oil prices, fears of global warming, and instability in oil-producing
      countries have ignited the rush to produce biofuels from plants. The science is
      progressing rapidly, driven by favorable policies and generous financing, but
      many hurdles remain before cars and trucks run on "gasohol" or "grassoline."

PMID- 19596228
TI  - Teeing up transcription on CpG islands.
AB  - Eukaryotic cells use elaborate molecular mechanisms to rapidly activate signal
      dependent gene expression. New work provides fresh insights into these mechanisms
      by demonstrating that CpG islands in promoters are nucleosome-destabilizing
      elements and can facilitate the establishment of an unusual poised
      transcriptional state (Ramirez-Carrozzi et al., 2009; Hargreaves et al., 2009).

PMID- 19596229
TI  - Disorder, promiscuity, and toxic partnerships.
AB  - Many genes are toxic when overexpressed, but general mechanisms for this toxicity
      have proven elusive. Vavouri et al. (2009) find that intrinsic protein disorder
      and promiscuous molecular interactions are strong determinants of dosage
      sensitivity, explaining in part the toxicity of dosage-sensitive oncogenes in
      mice and humans.

PMID- 19596230
TI  - Chromatin places metabolism center stage.
AB  - Dynamic changes in histone and transcription factor acetylation modulate gene
      expression. A study in Science (Wellen et al., 2009) reports that changes in
      glucose metabolism alter the availability of acetyl-CoA, the essential cofactor
      for protein acetylation. These findings reveal a direct connection between
      central metabolism and mammalian gene expression.

PMID- 19596231
TI  - Breaking up just got easier to do.
AB  - The SLX4 protein functions as a platform for catalytic subunits of structure
      specific endonucleases. Findings reported in Cell (Fekairi et al., 2009; Svendsen
      et al., 2009) and in Molecular Cell (Andersen et al., 2009; Munoz et al., 2009)
      now identify the human SLX4 and show that in association with the SLX1
      endonuclease it directs the symmetric cleavage and resolution of Holliday
      junctions.

PMID- 19596232
TI  - A positive spin on the centromere.
AB  - The properties of centromeric nucleosomes have been the subject of considerable
      debate and controversy. Furuyama and Henikoff (2009) now provide surprising
      evidence that centromeric nucleosomes wrap DNA in an orientation that is opposite
      to that of canonical nucleosomes.

PMID- 19596233
TI  - Getting to first base in proteasome assembly.
AB  - Assembly of complex structures such as the eukaryotic 26S proteasome requires
      intricate mechanisms that ensure precise subunit arrangements. Recent studies
      have shed light on the pathway for ordered assembly of the base of the 19S
      regulatory particle of the 26S proteasome by identifying new precursor complexes
      and four dedicated chaperones involved in its assembly.

PMID- 19596234
TI  - Redefining chronic viral infection.
AB  - Viruses that cause chronic infection constitute a stable but little-recognized
      part of our metagenome: our virome. Ongoing immune responses hold these chronic
      viruses at bay while avoiding immunopathologic damage to persistently infected
      tissues. The immunologic imprint generated by these responses to our virome
      defines the normal immune system. The resulting dynamic but metastable
      equilibrium between the virome and the host can be dangerous, benign, or even
      symbiotic. These concepts require that we reformulate how we assign etiologies
      for diseases, especially those with a chronic inflammatory component, as well as
      how we design and interpret genome-wide association studies, and how we vaccinate
      to limit or control our virome.

PMID- 19596235
TI  - Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for
      DNA repair.
AB  - Structure-specific endonucleases mediate cleavage of DNA structures formed during
      repair of collapsed replication forks and double-strand breaks (DSBs). Here, we
      identify BTBD12 as the human ortholog of the budding yeast DNA repair factor
      Slx4p and D. melanogaster MUS312. Human SLX4 forms a multiprotein complex with
      the ERCC4(XPF)-ERCC1, MUS81-EME1, and SLX1 endonucleases and also associates with
      MSH2/MSH3 mismatch repair complex, telomere binding complex TERF2(TRF2)
      TERF2IP(RAP1), the protein kinase PLK1 and the uncharacterized protein C20orf94.
      Depletion of SLX4 causes sensitivity to mitomycin C and camptothecin and reduces
      the efficiency of DSB repair in vivo. SLX4 complexes cleave 3' flap, 5' flap, and
      replication fork structures; yet unlike other endonucleases associated with SLX4,
      the SLX1-SLX4 module promotes symmetrical cleavage of static and migrating
      Holliday junctions (HJs), identifying SLX1-SLX4 as a HJ resolvase. Thus, SLX4
      assembles a modular toolkit for repair of specific types of DNA lesions and is
      critical for cellular responses to replication fork failure.

PMID- 19596236
TI  - Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA
      repair/recombination endonucleases.
AB  - Structure-specific endonucleases resolve DNA secondary structures generated
      during DNA repair and recombination. The yeast 5' flap endonuclease Slx1-Slx4 has
      received particular attention with the finding that Slx4 has Slx1-independent key
      functions in genome maintenance. Although Slx1 is a highly conserved protein in
      eukaryotes, no orthologs of Slx4 were reported other than in fungi. Here we
      report the identification of Slx4 orthologs in metazoa, including fly MUS312,
      essential for meiotic recombination, and human BTBD12, an ATM/ATR checkpoint
      kinase substrate. Human SLX1-SLX4 displays robust Holliday junction resolvase
      activity in addition to 5' flap endonuclease activity. Depletion of SLX1 and SLX4
      results in 53BP1 foci accumulation and H2AX phosphorylation as well as cellular
      hypersensitivity to MMS. Furthermore, we show that SLX4 binds the XPF(ERCC4) and
      MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 endonucleases and is required for
      DNA interstrand crosslink repair. We propose that SLX4 acts as a docking platform
      for multiple structure-specific endonucleases.

PMID- 19596237
TI  - Mammalian telomeres resemble fragile sites and require TRF1 for efficient
      replication.
AB  - Telomeres protect chromosome ends through the interaction of telomeric repeats
      with shelterin, a protein complex that represses DNA damage signaling and DNA
      repair reactions. The telomeric repeats are maintained by telomerase, which
      solves the end replication problem. We report that the TTAGGG repeat arrays of
      mammalian telomeres pose a challenge to the DNA replication machinery, giving
      rise to replication-dependent defects that resemble those of aphidicolin-induced
      common fragile sites. Gene deletion experiments showed that efficient duplication
      of telomeres requires the shelterin component TRF1. Without TRF1, telomeres
      activate the ATR kinase in S phase and show a fragile-site phenotype in
      metaphase. Single-molecule analysis of replicating telomeres showed that TRF1
      promotes efficient replication of TTAGGG repeats and prevents fork stalling. Two
      helicases implicated in the removal of G4 DNA structures, BLM and RTEL1, were
      required to repress the fragile-telomere phenotype. These results identify a
      second telomere replication problem that is solved by the shelterin component
      TRF1.

PMID- 19596238
TI  - Centromeric nucleosomes induce positive DNA supercoils.
AB  - Centromeres of higher eukaryotes are epigenetically maintained; however, the
      mechanism that underlies centromere inheritance is unknown. Centromere identity
      and inheritance require the assembly of nucleosomes containing the CenH3 histone
      variant in place of canonical H3. Although H3 nucleosomes wrap DNA in a left
      handed manner and induce negative supercoils, we show here that CenH3 nucleosomes
      reconstituted from Drosophila histones induce positive supercoils. Furthermore,
      we show that CenH3 likewise induces positive supercoils in functional centromeres
      in vivo, using a budding yeast minichromosome system and temperature-sensitive
      mutations in kinetochore proteins. The right-handed wrapping of DNA around the
      histone core implied by positive supercoiling indicates that centromere
      nucleosomes are unlikely to be octameric and that the exposed surfaces holding
      the nucleosome together would be available for kinetochore protein recruitment.
      The mutual incompatibility of nucleosomes with opposite topologies could explain
      how centromeres are efficiently maintained as unique loci on chromosomes.

PMID- 19596239
TI  - A unifying model for the selective regulation of inducible transcription by CpG
      islands and nucleosome remodeling.
AB  - We describe a broad mechanistic framework for the transcriptional induction of
      mammalian primary response genes by Toll-like receptors and other stimuli. One
      major class of primary response genes is characterized by CpG-island promoters,
      which facilitate promiscuous induction from constitutively active chromatin
      without a requirement for SWI/SNF nucleosome remodeling complexes. The low
      nucleosome occupancy at promoters in this class can be attributed to the assembly
      of CpG islands into unstable nucleosomes, which may lead to SWI/SNF independence.
      Another major class consists of non-CpG-island promoters that assemble into
      stable nucleosomes, resulting in SWI/SNF dependence and a requirement for
      transcription factors that promote selective nucleosome remodeling. Some stimuli,
      including serum and tumor necrosis factor-alpha, exhibit a strong bias toward
      activation of SWI/SNF-independent CpG-island genes. In contrast, interferon-beta
      is strongly biased toward SWI/SNF-dependent non-CpG-island genes. By activating a
      diverse set of transcription factors, Toll-like receptors induce both classes and
      others for an optimal response to microbial pathogens.

PMID- 19596240
TI  - Control of inducible gene expression by signal-dependent transcriptional
      elongation.
AB  - Most inducible transcriptional programs consist of primary and secondary response
      genes (PRGs and SRGs) that differ in their kinetics of expression and in their
      requirements for new protein synthesis and chromatin remodeling. Here we show
      that many PRGs, in contrast to SRGs, have preassembled RNA polymerase II (Pol II)
      and positive histone modifications at their promoters in the basal state. Pol II
      at PRGs generates low levels of full-length unspliced transcripts but fails to
      make mature, protein-coding transcripts in the absence of stimulation. Induction
      of PRGs is controlled at the level of transcriptional elongation and mRNA
      processing, through the signal-dependent recruitment of P-TEFb. P-TEFb is in turn
      recruited by the bromodomain-containing protein Brd4, which detects H4K5/8/12Ac
      inducibly acquired at PRG promoters. Our findings suggest that the permissive
      structure of PRGs both stipulates their unique regulation in the basal state by
      corepressor complexes and enables their rapid induction in multiple cell types.

PMID- 19596242
TI  - A systems-level analysis of perfect adaptation in yeast osmoregulation.
AB  - Negative feedback can serve many different cellular functions, including noise
      reduction in transcriptional networks and the creation of circadian oscillations.
      However, only one special type of negative feedback ("integral feedback") ensures
      perfect adaptation, where steady-state output is independent of steady-state
      input. Here we quantitatively measure single-cell dynamics in the Saccharomyces
      cerevisiae hyperosmotic shock network, which regulates membrane turgor pressure.
      Importantly, we find that the nuclear enrichment of the MAP kinase Hog1 perfectly
      adapts to changes in external osmolarity, a feature robust to signaling fidelity
      and operating with very low noise. By monitoring multiple system quantities
      (e.g., cell volume, Hog1, glycerol) and using varied input waveforms (e.g., steps
      and ramps), we assess in a minimally invasive manner the network location of the
      mechanism responsible for perfect adaptation. We conclude that the system
      contains only one effective integrating mechanism, which requires Hog1 kinase
      activity and regulates glycerol synthesis but not leakage.

PMID- 19596241
TI  - CarD is an essential regulator of rRNA transcription required for Mycobacterium
      tuberculosis persistence.
AB  - Mycobacterium tuberculosis is arguably the world's most successful infectious
      agent because of its ability to control its own cell growth within the host.
      Bacterial growth rate is closely coupled to rRNA transcription, which in E. coli
      is regulated through DksA and (p)ppGpp. The mechanisms of rRNA transcriptional
      control in mycobacteria, which lack DksA, are undefined. Here we identify CarD as
      an essential mycobacterial protein that controls rRNA transcription. Loss of CarD
      is lethal for mycobacteria in culture and during infection of mice. CarD
      depletion leads to sensitivity to killing by oxidative stress, starvation, and
      DNA damage, accompanied by failure to reduce rRNA transcription. CarD can
      functionally replace DksA for stringent control of rRNA transcription, even
      though CarD associates with a different site on RNA polymerase. These findings
      highlight a distinct molecular mechanism for regulating rRNA transcription in
      mycobacteria that is critical for M. tuberculosis pathogenesis.

PMID- 19596243
TI  - Myelin gene regulatory factor is a critical transcriptional regulator required
      for CNS myelination.
AB  - The transcriptional control of CNS myelin gene expression is poorly understood.
      Here we identify gene model 98, which we have named myelin gene regulatory factor
      (MRF), as a transcriptional regulator required for CNS myelination. Within the
      CNS, MRF is specifically expressed by postmitotic oligodendrocytes. MRF is a
      nuclear protein containing an evolutionarily conserved DNA binding domain
      homologous to a yeast transcription factor. Knockdown of MRF in oligodendrocytes
      by RNA interference prevents expression of most CNS myelin genes; conversely,
      overexpression of MRF within cultured oligodendrocyte progenitors or the chick
      spinal cord promotes expression of myelin genes. In mice lacking MRF within the
      oligodendrocyte lineage, premyelinating oligodendrocytes are generated but
      display severe deficits in myelin gene expression and fail to myelinate. These
      mice display severe neurological abnormalities and die because of seizures during
      the third postnatal week. These findings establish MRF as a critical
      transcriptional regulator essential for oligodendrocyte maturation and CNS
      myelination.

PMID- 19596244
TI  - Intrinsic protein disorder and interaction promiscuity are widely associated with
      dosage sensitivity.
AB  - Why are genes harmful when they are overexpressed? By testing possible causes of
      overexpression phenotypes in yeast, we identify intrinsic protein disorder as an
      important determinant of dosage sensitivity. Disordered regions are prone to make
      promiscuous molecular interactions when their concentration is increased, and we
      demonstrate that this is the likely cause of pathology when genes are
      overexpressed. We validate our findings in two animals, Drosophila melanogaster
      and Caenorhabditis elegans. In mice and humans the same properties are strongly
      associated with dosage-sensitive oncogenes, such that mass-action-driven
      molecular interactions may be a frequent cause of cancer. Dosage-sensitive genes
      are tightly regulated at the transcriptional, RNA, and protein levels, which may
      serve to prevent harmful increases in protein concentration under physiological
      conditions. Mass-action-driven interaction promiscuity is a single theoretical
      framework that can be used to understand, predict, and possibly treat the effects
      of increased gene expression in evolution and disease.

PMID- 19596245
TI  - SnapShot: Ca2+-calcineurin-NFAT signaling.

PMID- 19596252
TI  - Solid-state NMR approaches to measure topological equilibria and dynamics of
      membrane polypeptides.
AB  - Biological membranes are characterized by a high degree of dynamics. In order to
      understand the function of membrane proteins and even more of membrane-associated
      peptides, these motional aspects have to be taken into consideration. Solid-state
      NMR spectroscopy is a method of choice when characterizing topological
      equilibria, molecular motions, lateral and rotational diffusion as well as
      dynamic oligomerization equilibria within fluid phase lipid bilayers. Here we
      show and review examples where the (15)N chemical shift anisotropy, dipolar
      interactions and the deuterium quadrupolar splittings have been used to analyze
      motions of peptides such as peptaibols, antimicrobial sequences, Vpu,
      phospholamban or other channel domains. In particular, simulations of (15)N and
      (2)H-solid-state NMR spectra are shown of helical domains in uniaxially oriented
      membranes when rotation around the membrane normal or the helix long axis occurs.

PMID- 19596251
TI  - Mass spectral characterization of organophosphate-labeled lysine in peptides.
AB  - Organophosphate (OP) esters bind covalently to the active site serine of enzymes
      in the serine hydrolase family. Recently, mass spectrometry identified covalent
      binding of OPs to tyrosine in a wide variety of proteins when purified proteins
      were incubated with OPs. In the current work, manual inspection of tandem mass
      spectrometry (MS/MS) data led to the realization that lysines also make a
      covalent bond with OPs. OP-labeled lysine residues were found in seven proteins
      that had been treated with either chlorpyrifos oxon (CPO) or
      diisopropylfluorophosphate (DFP): human serum albumin (K212, K414, K199, and
      K351), human keratin 1 (K211 and K355), human keratin 10 (K163), bovine tubulin
      alpha (K60, K336, K163, K394, and K401), bovine tubulin beta (K58), bovine actin
      (K113, K291, K326, K315, and K328), and mouse transferrin (K296 and K626). These
      results suggest that OP binding to lysine is a general phenomenon. Characteristic
      fragments specific for CPO-labeled lysine appeared at 237.1, 220.0, 192.0, 163.9,
      128.9, and 83.9amu. Characteristic fragments specific for DFP-labeled lysine
      appeared at 164.0, 181.2, and 83.8amu. This new OP-binding motif to lysine
      suggests new directions to search for mechanisms of long-term effects of OP
      exposure and in the search for biomarkers of OP exposure.

PMID- 19596254
TI  - Genome profiling of chondrosarcoma using oligonucleotide array-based comparative
      genomic hybridization.
AB  - Chondrosarcomas of the bone are malignant hyaline cartilage-forming tumors with
      an annual incidence rate of 3.6% of all primary bone malignancies in the United
      States. Specimens of 25 chondrosarcomas (10 grade I, 9 grade II, 1 grade III, and
      5 dedifferentiated) from 23 patients were collected from the Department of
      Pathology at the University Hospital at UMDNJ-New Jersey Medical School from 1996
      to 2007. Array-based comparative genomic hybridization (array-CGH) studies were
      performed on frozen tumor specimens. Recurrent deletions observed in at least in
      six tumors were 5q13.2, 5q14.2 approximately q21.3, 6q12 approximately q13, 6q16
      approximately q25.3, 9p24.2 approximately q12, and 9p21.3. There was a
      statistically significant association between high-grade tumor (grade III and
      dedifferentiated) and the recurrent genetic deletions at 5q14.2 approximately
      q21.3, 6q16 approximately q25.3, 9p24.2 approximately q12, and 9p21.3. There is
      consistency between increased levels of aneuploidy and the progression of
      chondrosarcoma from lower to higher grades.

PMID- 19596255
TI  - Toll-like receptor 9 agonists promote IL-8 and TGF-beta1 production via
      activation of nuclear factor kappaB in PC-3 cells.
AB  - Chronic infection and resulting inflammation promote tumor development and
      progression, and Toll-like receptors (TLRs) may play an important role in this
      process. The aim of this study was to determine whether CpG oligonucleotides (CpG
      ODN), which are Toll-like receptor 9 (TLR9) agonists, can promote inflammatory
      cytokines release from the prostate cancer PC-3 cells through activation of
      nuclear factor-kappaB (NF-kappaB). Flow cytometry, semiquantitative real-time
      reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent
      assay, and immunofluorescence analysis were used to detect the transforming
      growth factor-beta1 (TGF-beta1) and interleukin-8 (IL-8) release and NF-kappaB
      activation in PC-3 cells after CpG-ODN stimulation. CpG-ODN promoted the
      expression and secretion of immunosuppressive cytokines TGF-beta1 and IL-8 from
      PC-3 cells. In addition, after CpG-ODN stimulation, NF-kappaB nuclear
      translocation was also observed in PC-3 cells, contributing to CpG-induced
      upregulation of IL-8 and TGF-beta1. Thus, TLR9 agonists may promote IL-8 and TGF
      beta1 production in human prostate cancer cells through NF-kappaB activation.

PMID- 19596256
TI  - Gain of chromosome arm 1q in patients in relapse and progression of multiple
      myeloma.
AB  - Abnormalities of chromosome 1 are among the most frequent chromosomal aberrations
      in patients with multiple myeloma (MM) and are considered a poor-risk genetic
      feature. To define the frequency and minimal region of 1q gain, we performed
      immunophenotyping and fluorescence in situ hybridization, comparative genomic
      hybridization (CGH), and array-CGH in 30 patients in relapse and progression of
      MM. Gain of 1q21 was found in 15 patients (50%), and in 14 of them whole-arm gain
      was found. One of these 14 patients had trisomy of chromosome 1 together with
      whole arm 1q gain, and two others had segmental duplication together with whole
      arm 1q gain. Segmental duplication of 1q21.1 approximately q23.1 alone was found
      in one patient. These results confirmed a high frequency of 1q aberrations and
      revealed that the vast majority of patients with 1q aberration in relapse and
      progression of MM display whole arm 1q gain. Finally, we observed that 1q gain is
      highly associated with number of additional changes.

PMID- 19596257
TI  - Collagenous fibroma (desmoplastic fibroblastoma) with a new translocation
      involving 11q12: a case report.
AB  - Collagenous fibroma (or desmoplastic fibroblastoma) is a rare, benign tumor
      usually centered in the subcutaneous tissue composed of spindle-shaped to
      stellate fibroblasts and myofibroblasts in a densely collagenous background.
      Three previous case reports have described a t(2;11)(q31;q12) in this entity.
      Herein, we report a case of collagenous fibroma of deep soft tissue with
      t(11;17)(q12;p11.2). The breakpoint at chromosome 11q12 appears to be
      pathogenetic in this rare neoplasm.

PMID- 19596258
TI  - MYC gene amplification in double minute chromosomes in an aggressive large B-cell
      lymphoma with leukemic presentation: a case report.
AB  - Double-minute chromosomes (dmin) are small chromatin particles that lack a
      centromere. They represent extrachromosomal form of gene amplification. Dmin are
      very rarely encountered in lymphoid neoplasms. We describe a case of a leukemic
      presentation of large B-cell lymphoma with dmin. Fluorescence in situ
      hybridization analysis identified these dmin as comprising MYC genes.

PMID- 19596259
TI  - Trisomy 8 in two newly diagnosed Chinese patients with chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid
      malignancies in Western countries, but is infrequent in Asian populations. To
      verify the incidence of trisomy 8 in Chinese patients with CLL, fluorescence in
      situ hybridization (FISH) was used in 140 CLL patients after routine chromosome
      analysis. Only two patients (1.4%) were found with trisomy 8, and the number of
      trisomy 8 cells was 8 and 10%, respectively. No other aberrations by "panel"
      probe FISH were found in these two patients. The chromosome karyotypes of two
      patients were 47,XY,+8[2]/49,XY,+14,+20,+21[2]/46,XY[16] and
      47,XX,+8[2]/46,XX[18], respectively. Neither of the patients' present signs of
      myelodysplastic or myeloproliferative disorder appeared on the bone marrow
      aspirates and peripheral blood smear. Our study demonstrates that trisomy 8 is
      rare in CLL, and its role in prognosis of CLL remains unknown.

PMID- 19596260
TI  - Loss of heterozygosity of succinate dehydrogenase B mutation by direct sequencing
      in synchronous paragangliomas.
AB  - Extraadrenal pheochromocytomas and paragangliomas are rare entities within the
      pediatric population. We report the presentation of three synchronous extra
      adrenal abdominal paragangliomas in an adolescent boy who carries a germline
      mutation in the succinate dehydrogenase B (SDHB) gene. Loss of heterozygosity of
      this allele was demonstrated by direct sequencing of DNA from two of his tumors,
      confirming loss of tumor suppressor function in the pathogenesis of these
      paragangliomas.

PMID- 19596261
TI  - Translocation (1;10)(p34;p15) in infant acute myeloid leukemia with
      extramedullary infiltration in multiple sites.
AB  - Primary acute myeloid leukemia (AML) with extramedullary infiltration (EMI) in
      multiple sites is rare. Herein, we describe a case of infant AML with EMI in
      multiple sites. She had dyspnea and hypofibrinogenemia at diagnosis, and systemic
      computed tomography revealed EMI in the orbit, gingiva, bronchial pathway, and
      urinary tract. Bone marrow examination confirmed the diagnosis of AML with
      t(1;10)(p34;p15). No case of AML with t(1;10)(p34;p15) has been reported in the
      literature. At the present time, she remains free of disease 12 months after bone
      marrow transplantation (BMT) in the second complete remission.

PMID- 19596262
TI  - A novel four-way t(6;16;21;8)(p21.3;p11.2;q22;q22) in acute myeloid leukemia with
      RUNX1/RUNX1T1 rearrangement.

PMID- 19596263
TI  - TP53 mutations and Arg72Pro polymorphism in breast cancers.

PMID- 19596264
TI  - Acute myeloid leukemia with MYC amplification in the homogeneous staining regions
      and double minutes.

PMID- 19596265
TI  - A new mutation in the MEN1 gene.

PMID- 19596266
TI  - Analysis of the progression of JAK2 V617F positive myeloproliferative neoplasms
      by single-nucleotide polymorphism array does not reveal a strong chromosomal
      instability.

PMID- 19596267
TI  - How 7-month-olds interpret ambiguous motion events: category-based reasoning in
      infancy.
AB  - This paper investigates the role of static and dynamic attributes for the animate
      inanimate distinction in category-based reasoning of 7-month-olds. Three
      experiments tested infants' responses to movement events involving an unfamiliar
      animal and a ball. When either the animal or the ball showed self-initiated
      irregular movements (Experiment 1), infants expected the previously active object
      to start moving again. When both objects were moving together in an ambiguous
      motion event (Experiment 2), infants expected only the animal to start moving
      again. Initial looking preferences for each object did not influence results.
      When either the facial features of the animal were removed, or its furry body was
      replaced by a plastic spiral in an ambiguous motion event (Experiment 3), infants
      formed no clear expectation regarding future movements. Based on this set of
      findings we conclude that 7-month-olds flexibly combine information about the
      static and dynamic properties of objects in order to reason about motion events.

PMID- 19596268
TI  - Increased galectin-7 gene expression in lymphoma cells is under the control of
      DNA methylation.
AB  - Recent studies have reported that elevated levels of galectin-7 in different
      types of cancer. The mechanisms underlying its abnormal regulation in cancer
      cells remain, however, unknown. Here, we have examined the relationship between
      galectin-7 and p53, a gene previously associated with upregulation of galectin-7.
      While RNA and protein analyses revealed a consistent and irreversible
      upregulation of galectin-7 throughout progression of lymphoma, no correlation
      with p53 was found. In fact, most of the lymphoma cell lines expressing high
      levels of galectin-7 did not express any detectable level of p53, although
      expressed p21(Waf1/Cip1) gene following doxorubicin treatment, indicating that
      p53 was functional in these cells. Methylation-specific polymerase chain reaction
      (MS-PCR) analyses rather suggested that galectin-7 expression was associated with
      changes in DNA methylation. This conclusion was supported by data using
      demethylating agent 5-aza-dC. Furthermore, disruption of the DNA methylases dnmt1
      and dnmt3a induced galectin-7. Collectively, our data suggest that abnormal
      expression of galectin-7 in lymphoma cells is not dependent on p53, but is rather
      associated with DNA hypomethylation.

PMID- 19596269
TI  - HDAC inhibitors, MS275 and SBHA, enhances cytotoxicity induced by oxaliplatin in
      the colorectal cancer cell lines.
AB  - Histone deacetylases (HDACs) play an important role in the epigenetic regulation
      of gene expression by catalyzing the removal of acetyl groups, stimulating
      chromatin condensation, and promoting transcriptional repression. Since aberrant
      epigenetic changes are a hallmark of cancer, HDACs appear a promising target for
      pharmacological inhibition. To test this we have addressed the hypothesis that
      histone deacetylase inhibitors (HDACi), MS275 and SBHA, potentiate inhibitory
      effects of classical anti-colorectal cancer cytostatic, oxaliplatin, on survival
      of colorectal cancer (CRC) cells in vitro. We are reporting here that HDACi shows
      potent synergistic interaction with oxaliplatin. The observed synergism between
      HDACi and oxaliplatin is most probably related to the augmented apoptotic signal
      and allowed for significant reduction of doses of anticancer agents used.

PMID- 19596270
TI  - Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.
AB  - Interleukin (IL)-33 is a novel member of the IL-1 family. IL-33 is primarily
      synthesized as a 30-kDa precursor (pro-IL-33). Pro-IL-33 is cleaved by caspase-1
      into an 18-kDa mature form (mature IL-33) in vitro. Recombinant mature IL-33 has
      been known to induce T-helper type-2 (Th2)-associated cytokines and inflammatory
      cytokines via its receptor, ST2L. However, processing of pro-IL-33 in vivo has
      not been clarified yet. Here, we report that calpain mediates pro-IL-33
      processing in vivo. Pro-IL-33 was expressed by stimulating human epithelial cells
      with phorbol 12-myristate 13-acetate. Calcium ionophore induced pro-IL-33
      cleavage and mature IL-33 production. This cleavage was inhibited by treatment
      with a calcium chelator and calpain inhibitors. Moreover, short interfering RNA
      mediated knockdown of calpains suppressed pro-IL-33 cleavage. These results
      indicate that calpains play a critical role in pro-IL-33 processing in vivo.

PMID- 19596271
TI  - Chronic alcohol consumption prevents 8-hydroxyguanine accumulation in 3'-methyl-4
      dimethylaminoazobenzene-treated mouse liver.
AB  - Alcohol consumption is known to have opposing effects on carcinogenesis:
      promotion and prevention. In this study, we examined the effects of 12% ethanol
      on oxidative DNA damage accumulation and its repair in mouse livers treated with
      3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), a well-known hepatic carcinogen.
      We previously reported that 3'-MeDAB increased 8-hydroxyguanine (8-OH-Gua)
      accumulation and its repair activity, accompanied by the fragmentation of 8
      oxoguanine DNA glycosylase 1 (OGG1), the main repair enzyme of 8-OH-Gua. The
      present results showed that 12% ethanol intake attenuated the 8-OH-Gua
      accumulation, but not the fragmentation of OGG1 induced by 3'-MeDAB.
      Additionally, no significant changes in oxidative status, as monitored by lipid
      peroxidation (LPO), were observed among the 3'-MeDAB-treated mouse livers
      with/without alcohol administration. These findings suggested that 12% ethanol
      consumption may reduce the risk of 3'-MeDAB-induced carcinogenesis by decreasing
      8-OH-Gua accumulation.

PMID- 19596272
TI  - A filter bank-based source extraction algorithm for heart sound removal in
      respiratory sounds.
AB  - In this paper, we consider the problem of heart sounds (HS) removal from
      respiratory sounds (RS), and a novel semi-blind single-channel source extraction
      algorithm is proposed. The proposed method is able to extract the underlying pure
      RS from the HS corrupted noisy input signals by incorporating the filter banks
      and template-based matching using FIR filters. For performance evaluation of the
      presented method, the average power spectral densities (PSD) of the input RS
      segments without HS have been compared with the PSD of the reconstructed signals
      over six selected frequency bands from 20 to 800Hz. The proposed method is tested
      for various types of RS recordings and found effective by yielding an overall
      maximum spectral difference of 2.8707+/-0.9875dB for a frequency range below
      800Hz.

PMID- 19596273
TI  - Modified sound-evoked brainstem potentials in Foxp2 mutant mice.
AB  - Heterozygous mutations of the human FOXP2 gene cause a developmental disorder
      involving impaired learning and production of fluent spoken language. Previous
      investigations of its aetiology have focused on disturbed function of neural
      circuits involved in motor control. However, Foxp2 expression has been found in
      the cochlea and auditory brain centers and deficits in auditory processing could
      contribute to difficulties in speech learning and production. Here, we recorded
      auditory brainstem responses (ABR) to assess two heterozygous mouse models
      carrying distinct Foxp2 point mutations matching those found in humans with FOXP2
      related speech/language impairment. Mice which carry a Foxp2-S321X nonsense
      mutation, yielding reduced dosage of Foxp2 protein, did not show systematic ABR
      differences from wildtype littermates. Given that speech/language disorders are
      observed in heterozygous humans with similar nonsense mutations (FOXP2-R328X),
      our findings suggest that auditory processing deficits up to the midbrain level
      are not causative for FOXP2-related language impairments. Interestingly, however,
      mice harboring a Foxp2-R552H missense mutation displayed systematic alterations
      in ABR waves with longer latencies (significant for waves I, III, IV) and smaller
      amplitudes (significant for waves I, IV) suggesting that either the synchrony of
      synaptic transmission in the cochlea and in auditory brainstem centers is
      affected, or fewer auditory nerve fibers and fewer neurons in auditory brainstem
      centers are activated compared to wildtypes. Therefore, the R552H mutation
      uncovers possible roles for Foxp2 in the development and/or function of the
      auditory system. Since ABR audiometry is easily accessible in humans, our data
      call for systematic testing of auditory functions in humans with FOXP2 mutations.

PMID- 19596274
TI  - Effects of repeated citalopram treatment on kainic acid-induced neurogenesis in
      adult mouse hippocampus.
AB  - Previous studies have demonstrated that systemic administration of kainic acid
      (KA) triggers a cascade of neuroplastic changes in the hippocampus. Intensive
      neurodegeneration accompanied by immune response and enhanced neurogenesis
      following local or systemic KA administration in rats and mice has been reported.
      KA-induced enhancement in proliferative activity of neuronal and glial precursors
      results in the appearance of immature hyperactive neurons which could be regarded
      as evidence of dysregulated neural plasticity. In this study we attempted to
      investigate whether administration of selective serotonin reuptake inhibitor
      (SSRI) citalopram could inhibit KA-induced reactive gliosis and dysregulated
      neurogenesis in mice. The results of our study demonstrate that repeated
      administration of citalopram counteracted KA-induced reactive gliosis and reduced
      aberrant proliferative activity in the dentate gyrus of the mouse brain. We found
      that the population of BrdU-positive cells expressing markers for young neurons
      was decreased following repeated citalopram administration compared to KA-treated
      animals. These results suggest that repeated citalopram administration could
      prevent activation of aberrant neuroplasticity in the damaged hippocampus.

PMID- 19596276
TI  - Memantine blocks sensitization to the rewarding effects of morphine.
AB  - Knowledge regarding the specific brain changes and neural plasticity processes
      produced by repeated drug exposure may be used to advance the understanding of
      the neurobiology of addiction in order to design appropriate medications. In the
      present study, the influence of N-methyl-d-aspartate (NMDA) glutamatergic
      receptors on sensitization to the motor and rewarding effects of morphine was
      evaluated. The effects of pre-exposure to saline or 20 mg/kg morphine plus the
      NMDA receptor antagonist memantine (10 or 20 mg/kg) on motor activity and place
      conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The dose
      of 2 mg/kg of morphine was ineffective in mice pre-exposed to saline but induced
      a clear conditioned place preference (CPP) in those pre-exposed to morphine.
      Conversely, animals pre-exposed to morphine plus memantine did not acquire CPP.
      Only those pre-exposed to morphine presented an increased motor response to
      morphine 2 mg/kg. Our results demonstrate that NMDA glutamatergic receptors are
      implicated in the development of sensitization to the conditioned rewarding
      effects of morphine.

PMID- 19596275
TI  - Estrogen receptor alpha and beta specific agonists regulate expression of
      synaptic proteins in rat hippocampus.
AB  - Changes in hippocampal CA1 dendritic spine density and synaptic number across the
      estrous cycle in female rats correlate with increased hippocampal-dependent
      cognitive performance in a manner that is dependent on estrogen receptors (ERs).
      Two isoforms of the estrogen receptor, alpha and beta are present in the rat
      hippocampus and distinct effects on cognitive behavior have been described for
      each receptor. The present study generated a profile of synaptic proteins altered
      by administration of estradiol benzoate, the ERalpha selective agonist PPT (1,3,5
      tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole) and the ERbeta selective agonist DPN
      (2,3-bis (4-hydroxyphenyl) propionitrile) alone and in combination in comparison
      to vehicle in the CA1 region of the dorsal hippocampus. In the stratum radiatum,
      estradiol, DPN, and PPT increased PSD-95 and AMPA-type glutamate receptor subunit
      GluR1. Only DPN administration regulated expression of AMPA receptor subunits
      GluR2 and GluR3, increasing and decreasing levels respectively. DPN also
      increased GluR2 expression in the other lamina of the CA1. These results support
      previous reports that estradiol and isoform specific agonists differentially
      activate ERalpha and ERbeta to regulate protein expression. The distinct effects
      of DPN and PPT administration on synaptic proteins suggest that the desired
      therapeutic outcome of estrogen may be accomplished by using specific estrogen
      receptor agonists. Moreover, the effects of estradiol treatment on PSD-95
      expression are consistent with a growing body of evidence that this postsynaptic
      protein is a key marker of estrogen action related to spine synapse formation.

PMID- 19596278
TI  - Synergistic effects of osteonectin and NGF in promoting survival and neurite
      outgrowth of superior cervical ganglion neurons.
AB  - Schwann cells (SCs) play a major role in the successful regeneration of
      peripheral nerves regeneration. Here we examined the effects of osteonectin (ON),
      a major factor secreted by SCs, on survival and neuritogenesis of mouse superior
      cervical ganglion (SCG) neurons. SC conditioned medium (SCCM) not only promoted
      the survival and neuritogenesis of SCG neurons at a level comparable to nerve
      growth factor (NGF) but also doubled the neurite length of NGF-treated SCG
      neurons. SCCM neuritogenic effects were not blocked by the tyrosine kinase
      receptor (Trk) inhibitor K252a demonstrating that these are not due solely to
      classical neurotrophic factors. Anti-ON neutralizing antibody diminished the SCCM
      induced survival and neuritogenesis significantly. In the presence of K252a, the
      SCCM neuritogenic effects were blocked completely by anti-ON which suggests
      synergistic effects of ON with Trk-mediated growth factors. ON alone increased
      the survival and neurite outgrowth of SCG neurons significantly at high density
      cultures. ON at low concentration acts synergistically with NGF which induced
      maximum survival and neurite outgrowth (>50% increase). However, ON at high
      concentration was detrimental to survival (64% decrease) and neurite outgrowth
      (87% decrease) even in the presence of NGF. The well documented counter-adhesive
      effect of ON may account for this observation. Nevertheless, the growth promoting
      effects of ON became more pronounced as the cell density increased which suggests
      a possible interaction of ON with growth factors secreted by SCG neurons
      (autocrine or paracrine effects). Taken together, our study indicates that ON
      plays important roles in nervous system repair through its synergistic effects
      with growth factors.

PMID- 19596277
TI  - The effects of Parkinson's disease and age on syncopated finger movements.
AB  - In young healthy adults, syncopated finger movements (movements between
      consecutive beats) are characterized by a frequency-dependent change in phase at
      movement rates near 2 Hz. A similar frequency-dependent phase transition is
      observed during bimanual anti-phase (asymmetric) tasks in healthy young adults,
      but this transition frequency is significantly lowered in both patients with
      Parkinson's disease (PD) and older adults. To date, no study has examined the
      transition frequency associated with unimanual syncopated movements in patients
      with PD or older adults. This study examined the effects of movement frequency on
      the performance of unconstrained syncopated index finger flexion movements in
      patients with PD, older adult subjects matched to patients with PD, and young
      adult subjects. Syncopated movements were paced by an acoustic tone that
      increased in frequency from 1 to 3 Hz in 0.25 Hz increments. Movement phase was
      quantified and the movement frequency where subjects transitioned from
      syncopation to synchronization was compared between groups. The principal finding
      was a marked impairment in the ability of patients with PD to perform syncopated
      movements when off medication. Medication did not significantly improve
      performance. In addition, the transition frequency for older adult subjects was
      lower than young adult subjects. These findings demonstrate that, similar to
      bimanual tasks, the coordination dynamics associated with unimanual syncopated
      finger movements transition from a stable to an unstable pattern at significantly
      lower frequencies in patients with PD and older adults compared to young adults.

PMID- 19596279
TI  - Tonic inhibition of somatostatin on C and Adelta afferent fibers in rat dorsal
      skin in vivo.
AB  - The purpose of this study was to investigate the effect of somatostatin (SST) in
      peripheral nerve terminals using local application of the SST receptor (SSTR)
      antagonist cyclo-somatostatin (c-SOM) injected into the receptive fields of
      cutaneous afferent fibers innervating the dorsal hairy skin in anesthetized rats.
      Single unit activity was recorded in teased filaments from the dorsal cutaneous
      nerve branch. Recordings were obtained from 206 primary afferent fibers. They
      were classified as C (n=70), Adelta (n=84) or Abeta (n=52) fibers based upon
      their conduction velocity. For C and Adelta fibers, mean discharge rate increased
      and mechanical threshold decreased significantly to 10 microL of 12.8 and 128
      microM injected subcutaneously, but not to 0.128 and 1.28 microM c-SOM injection.
      For Abeta fibers, no dose of c-SOM changed their discharge rate or their
      mechanical sensitivity. In control experiments, injection of normal saline (NS)
      had no effect on any of the units tested. Octreotide (20 microM, 10 microL), an
      SSTR agonist, successfully reversed the increase in discharge rates and the
      decrease in mechanical thresholds in C and Adelta fibers when it was pre
      administrated into the receptive field before c-SOM injection. These results
      provide evidence that somatostatin tonically inhibits the peripheral nerve
      terminals of small-diameter cutaneous afferent fibers.

PMID- 19596280
TI  - Myelination of the corpus callosum in male and female rats following complex
      environment housing during adulthood.
AB  - Myelination is an important process in brain development, and delays or
      abnormalities in this process have been associated with a number of conditions
      including autism, developmental delay, attention deficit disorder, and
      schizophrenia. Myelination can be sensitive to developmental experience; however,
      although the adult brain remains highly plastic, it is unknown whether
      myelination continues to be sensitive to experience during adulthood. Male and
      female rats were socially housed until four months of age, at which time they
      were moved into either a complex or "enriched" environment (EC) or an isolated
      condition (IC). Although the area of the splenium (posterior 20% of the callosum,
      which contains axons from visual cortical neurons) increased by about 10%
      following two months of EC housing, the area occupied by myelinated axons was not
      influenced by adult housing condition. Instead, it was the area occupied by glial
      cell processes and unmyelinated axons which significantly increased following EC
      housing. Neither the size nor the myelin content of the genu (anterior 15% of the
      callosum) was sensitive to manipulations of adult housing condition, but males
      had more area occupied by myelinated axons in both callosal regions. Finally, the
      inability of two months of complex environment housing during adulthood to impact
      the number of myelinated axons in the splenium was confirmed in a subset of
      animals using quantitative electron microscopy. We conclude that the sensitivity
      of myelination to experience is reduced in adulthood relative to development in
      both sexes.

PMID- 19596281
TI  - Brain and retinal ferroportin 1 dysregulation in polycythaemia mice.
AB  - Disruption of iron homeostasis within the central nervous system (CNS) can lead
      to profound abnormalities during both development and aging in mammals. The
      radiation-induced polycythaemia (Pcm) mutation, a 58-bp microdeletion in the
      promoter region of ferroportin 1 (Fpn1), disrupts transcriptional and post
      transcriptional regulation of this pivotal iron transporter. This regulatory
      mutation induces dynamic alterations in peripheral iron homeostasis such that
      newborn homozygous Pcm mice exhibit iron deficiency anemia with increased
      duodenal Fpn1 expression while adult homozygotes display decreased Fpn1
      expression and anemia despite organismal iron overload. Herein we report the
      impact of the Pcm microdeletion on iron homeostasis in two compartments of the
      central nervous system: brain and retina. At birth, Pcm homozygotes show a marked
      decrease in brain iron content and reduced levels of Fpn1 expression.
      Upregulation of transferrin receptor 1 (TfR1) in brain microvasculature appears
      to mediate the compensatory iron uptake during postnatal development and iron
      content in Pcm brain is restored to wild-type levels by 7 weeks of age.
      Similarly, changes in expression are transient and expression of Fpn1 and TfR1 is
      indistinguishable between Pcm homozygotes and wild-type by 12 weeks of age.
      Strikingly, the adult Pcm brain is effectively protected from the peripheral iron
      overload and maintains normal iron content. In contrast to Fpn1 downregulation in
      perinatal brain, the retina of Pcm homozygotes reveals increased levels of Fpn1
      expression. While retinal morphology appears normal at birth and during early
      postnatal development, adult Pcm mice demonstrate a marked, age-dependent loss of
      photoreceptors. This phenotype demonstrates the importance of iron homeostasis in
      retinal health.

PMID- 19596282
TI  - Bilateral high frequency stimulation of the subthalamic nucleus normalizes COX
      activity in the substantia nigra of Parkinsonian rats.
AB  - Part of the mechanism underlying the therapeutic effect of subthalamic nucleus
      (STN) high frequency stimulation (HFS) involves the activity of the basal ganglia
      output structures. The general idea is that STN's burst activity leads to an
      increased activity of the basal ganglia output nuclei and that HFS reverses this.
      However, the published data sets conflict. Here, we addressed the question which
      effect STN HFS had on the overall substantia nigra pars reticulata (SNr; one of
      the basal ganglia output nuclei) activity, in rats rendered Parkinsonian by 6
      hydroxydopamine (6-OHDA) injections in the striatum. We used a marker for
      metabolic activity, cytochrome C oxidase (COX). The expression of COX in the SNr
      of Parkinsonian rats was significantly higher as compared to sham-operated rats.
      However, in Parkinsonian rats with STN HFS, expression of COX was significantly
      lower as compared to non-stimulated Parkinsonian rats, and was comparable to the
      level of expression in sham-operated rats. These results show that STN HFS
      decreased the overall activity of the basal ganglia output nucleus in dopamine
      depleted rats.

PMID- 19596283
TI  - A nerve model of greatly increased energy-efficiency and encoding flexibility
      over the Hodgkin-Huxley model.
AB  - A mammalian "RGC model" (retinal ganglion cells) is distinguished from the
      Hodgkin-Huxley model by the virtual absence of K-current during, and the virtual
      absence of Na-current after, the regenerative (rising) phase of the action
      potential. Both Na- and K-currents remain negligible throughout the interspike
      interval, whose control is therefore relinquished to stimulus currents. These
      properties yield a highly flexible and energy-efficient nerve impulse encoder.
      For the Hodgkin-Huxley model, in contrast, only 15% of the Na-ions enter the axon
      regeneratively during the action potential (squid giant axon); a wasteful 85%
      enter during the falling phase. Further, early activation of K-current causes the
      Na- and K-currents of the action potential to dominate over stimulus currents in
      controlling the sub-threshold membrane potential (interspike interval). This
      property makes the Hodgkin-Huxley model an intractable high frequency oscillator,
      which cannot be converted to flexible impulse encoding. The temperature
      difference between the squid giant axon (6.3 degrees C) and RGCs (37 degrees C)
      is bridged by a Q10 analysis, which suggests that an additional molecular gating
      mechanism of high Q10 - which is not present in the squid - is active in RGCs.

PMID- 19596285
TI  - Cholinesterase inhibitory activities of some flavonoid derivatives and chosen
      xanthone and their molecular docking studies.
AB  - Flavonoids are one of the largest classes of plant secondary metabolites and are
      known to possess a number of significant biological activities for human health.
      In this study, we examined in vitro acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives-
      quercetin, rutin, kaempferol 3-O-beta-D-galactoside and macluraxanthone. The in
      vitro results showed that quercetin and macluraxanthone displayed a concentration
      dependant inhibition of AChE and BChE. Macluraxanthone showed to be the most
      potent and specific inhibitor of both the enzymes having the IC(50) values of
      8.47 and 29.8 microM, respectively. The enzyme kinetic studies revealed that
      quercetin inhibited both the enzymes in competitive manner, whereas the mode of
      inhibition of macluraxanthone was non-competitive against AChE and competitive
      against BChE. The inhibitory profiles of the compounds have been compared with
      standard AChE inhibitor galanthamine. To get insight of the intermolecular
      interactions, the molecular docking studies of these two compounds were performed
      at the active site 3D space of both the enzymes, using ICM-Dock module. Docking
      studies exhibited that macluraxanthone binds much more tightly with both the
      enzymes than quercetin. The calculated docking and binding energies also
      supported the in vitro inhibitory profiles (IC(50) values). Both the compounds
      showed several strong hydrogen bonds to several important amino acid residues of
      both the enzymes. A number of hydrophobic interactions could also explain the
      potency of the compounds to inhibit AChE and BChE.

PMID- 19596284
TI  - Acrolein induces a cellular stress response and triggers mitochondrial apoptosis
      in A549 cells.
AB  - Acrolein is a highly reactive, alpha,beta-unsaturated aldehyde that is an
      omnipresent environmental pollutant. Humans are exposed to acrolein in food,
      vapors of overheated cooking oil, cigarette smoke and by combustion of organic
      products. Acrolein is a toxic by-product of lipid peroxidation resulting from
      oxidative stress, which is implicated in pulmonary, cardiac and neurodegenerative
      diseases. Low dose exposure to toxic compounds often leads to adaptive responses.
      If the adaptive response does not counteract the adverse exposure, death
      processes such as apoptosis will eliminate the cell. This study investigates the
      activation of antiapoptosis survival factors in relation to the induction of cell
      death by apoptosis, following exposure to low doses of acrolein, in A549 human
      lung cells. Exposure to acrolein (<15microM, 30min) activated the survival factor
      AKT, which led to phosphorylation of Bad and induction of antiapoptosis proteins
      cIAP1/2. Acrolein (10-50microM, 30-60min) increased reactive oxygen species and
      caused mitochondrial membrane hyperpolarisation. Inhibition by the antioxidants
      catalase, polyethylene glycol-catalase, sodium pyruvate and MnTBAP showed that
      acrolein-induced reactive oxygen species were responsible for mitochondrial
      membrane hyperpolarisation. Acrolein (3-27microM, 30-60min) activated early stage
      processes in the mitochondrial pathway of apoptosis, such as Bax translocation to
      mitochondria, cytochrome c release, caspase-9 activation, and translocation of
      apoptosis-inducing factor to the nucleus. Acrolein (10-50microM) triggered later
      stage processes such as activation of caspases-3, -7 and -6, phosphatidylserine
      externalization and cleavage of poly(ADP)ribose polymerase after longer times
      (2h). These events were inhibited by polyethylene glycol-catalase, showing that
      apoptosis was mediated by overproduction of reactive oxygen species by acrolein.
      The novel findings show that antiapoptosis processes dominate at low dose
      (<15microM)/shorter exposure times to acrolein, whereas proapoptotic processes
      dominate at higher dose (10-50microM)/longer exposure times. Acrolein induced
      apoptosis through the mitochondrial pathway that was mediated by reactive oxygen
      species.

PMID- 19596286
TI  - Biochemical markers in sickle cell disease in a Brazilian population.

PMID- 19596287
TI  - The four Cs of care. Reflections on patient care from both sides of the
      stretcher.

PMID- 19596289
TI  - Give it back.

PMID- 19596291
TI  - On the same page. Standardizing prehospital care & staffing.

PMID- 19596292
TI  - Job huntin'. Preparing for the next opportunity.

PMID- 19596293
TI  - Handles for people revisiting the Montana blanket roll.

PMID- 19596294
TI  - The other TB. How to treat extrapulmonary tuberculosis & protect yourself.

PMID- 19596295
TI  - Cardio moves. An 'ounce of prevention' goes a long way.

PMID- 19596296
TI  - To err is human. Creating a 'just culture' to alter behavior & reduce medical
      errors.

PMID- 19596297
TI  - Survive your next shift. Tactics to defend yourself against violence.

PMID- 19596298
TI  - Cardiocerebral resuscitation. Improving cardiac arrest survival with a new
      technique.

PMID- 19596299
TI  - From sidelined to inline. Be ready & equipped to treat athletic C-spine injuries
      in & on the field.

PMID- 19596300
TI  - Proof of life. Why we must make every possible effort, even when patients 'look'
      dead.

PMID- 19596301
TI  - Striking out at stroke. A comparative perspective from South east Coast Ambulance
      Service in the United Kingdom.

PMID- 19596302
TI  - Spurs & backboards. Working the NASCAR of the west.

PMID- 19596303
TI  - The diagnostic value of soluble CD163 in patients presenting with chest pain.
AB  - BACKGROUND: CD163 is a scavenger receptor for the uptake of haptoglobin
      hemoglobin (Hpt-Hb) complexes. The Hpt-Hb complexes are being formed in the
      plaque in response to intraplaque hemorrhage, a hallmark of atherosclerotic
      plaque instability. We therefore investigated whether soluble CD163 (sCD163) was
      elevated in patients with an acute coronary syndrome. METHODS: All subjects
      presenting with chest pain suggestive of myocardial ischemia referred to either
      the emergency department or the coronary care unit were included in a prospective
      follow-up study. Plasma was collected and frozen at -80 degrees C until assayed.
      sCD163 was measured using a commercially available Elisa assay. RESULTS: Of 526
      included chest pain patients, the final diagnosis was non-cardiac chest pain in
      244 (46%) patients, non-STEMI in 67 (13%), and STEMI in 215 (41%). The non-STEMI
      patients were older, used more medication, had undergone more often coronary
      interventions, but did not differ with respect to risk factors, except for a
      higher incidence in dyslipidemia. Unexpectedly, sCD163 did not differentiate
      between patients with non-STEMI or STEMI and the non-cardiac chest pain patients
      (2.09+/-0.76 versus 2.24+/-0.86). CONCLUSION: Although ACS is characterized by
      intraplaque hemorrhage, the amount of intraplaque Hb release seems not to be
      substantial enough to result in a measurable difference in sCD163.

PMID- 19596309
TI  - Calculating cumulative live-birth rates from linked cycles of assisted
      reproductive technology (ART): data from the Massachusetts SART CORS.
AB  - OBJECTIVE: To determine the feasibility of linking assisted reproductive
      technology (ART) cycles for individual women to compare per-cycle and cumulative
      live-birth rates. DESIGN: Historical cohort study. SETTING: Clinic-based data.
      PATIENT(S): A total of 27,906 ART cycles with residency or treatment in
      Massachusetts during 2004-2006 and reported to the Society for Assisted
      Reproductive Technology Clinic Outcomes Reporting System (SART CORS) on-line
      database. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Per-cycle and
      cumulative live-birth rates. RESULT(S): Linkage of cycles up to and including the
      first live-birth delivery revealed 14,265 women who averaged 1.9+/-1.2 SD cycles
      (range 1-11). These cycles yielded 9,452 pregnancies resulting in 7,675 live
      birth deliveries. From cycle 1 to cycle 4, the cumulative live-birth rate for all
      patients increased from 30.4% to 43.3%, 49.1%, and 51.9%, respectively, and
      plateaued thereafter at about 53%. The cumulative live-birth rate after three
      cycles using donor oocytes was approximately 60% for women aged<43 years and >50%
      for women>or=43 years; for autologous oocytes it was 60.1% for ages<35 years and
      declined steadily to 8.5% for ages>or=43 years. CONCLUSION(S): The results
      demonstrate the feasibility of linking ART cycles for individual women from SART
      CORS to characterize cumulative live-birth rates.

PMID- 19596311
TI  - Altered distribution of plasma platelet-activating factor acetylhydrolase between
      high-density lipoprotein and low-density lipoprotein in patients with polycystic
      ovary syndrome.
AB  - To investigate the association of plasma platelet-activating factor (PAF)
      acetylhydrolase, high-density lipoprotein-associated PAF acetylhydrolase, and low
      density lipoprotein-associated PAF acetylhydrolase activities with metabolic
      features in patients with polycystic ovary syndrome (PCOS) in Han Chinese women,
      141 patients with PCOS and 140 healthy controls were recruited in this case
      control study. The results of our study showed that the presence of the changed
      plasma PAF acetylhydrolase activity and distribution in women with PCOS could
      contribute to the low-grade chronic inflammation and increased risk of
      atherosclerosis in these patients.

PMID- 19596310
TI  - The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for fertility.
AB  - OBJECTIVE: To determine the role of Dkkl1 on mouse development, viability, and
      fertility. DESIGN: Prospective experimental study. SETTING: Government research
      institution. ANIMAL(S): Mice of C57BL/6 and 129X1/SvJ strains, as well as
      transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies.
      INTERVENTION(S): Mice were constructed that lacked a functional Dkkl1 gene. MAIN
      OUTCOME MEASURE(S): Deletion of the gene was confirmed by DNA, RNA, and protein
      analyses; in vivo fertility was examined by continuous mating scheme. RESULT(S):
      Previous studies have shown that Dkkl1, a gene unique to mammals, is expressed
      predominantly, if not exclusively, in developing spermatocytes, and the DKKL1
      protein accumulates in the acrosome of mature sperm. Subsequent studies (reported
      in the accompanying article) demonstrate that Dkkl1 also is expressed in the
      trophectoderm/placental lineage. Taken together, these results strongly suggested
      that DKKL1 protein is required for terminal differentiation either of trophoblast
      giant cells or of sperm, both of which are directly involved in fertility. To
      challenge this hypothesis, conditional targeted mutagenesis was used to ablate
      the Dkkl1 gene in mice. Surprisingly, Dkkl1 nullizygous embryos developed into
      viable, fertile adults, despite the fact that they failed to produce any portion
      of the DKKL1 protein. CONCLUSION(S): DKKL1 is a mammalian-specific acrosomal
      protein that is not essential either for development or fertility.

PMID- 19596313
TI  - Morphologic indicators predict the stage of chromatin condensation of human
      germinal vesicle oocytes recovered from stimulated cycles.
AB  - OBJECTIVE: To assess germinal vesicles (GV) recovered from stimulated cycles by
      means of morphometric and morphologic examination (using contrast-phase and image
      analysis) and chromatin configuration (using fluorescent DNA imaging), and to
      evaluate the relevance of morphometric and morphologic parameters as forecasters
      of chromatin status. DESIGN: Experimental study. SETTING: University-affiliated
      infertility clinic. PATIENT(S): One hundred and thirty-one GV oocytes donated to
      patients for intracytoplasmic sperm injection. INTERVENTION(S): We evaluated 131
      GVs by means of morphology and morphometry with the use of contrast phase
      microscopy. They were subsequently fixed, DNA stained, and assessed by
      fluorescent microscopy. Compiled data were retrospectively grouped according to
      three models. MAIN OUTCOME MEASURE(S): Model A: ova were grouped according to
      chromatin condensation (noncondensed vs. condensed). Model B: ova were grouped
      according to chromatin distribution in relation to the nucleolus-like body (NLB)
      (not surrounding vs. surrounding and/or absent) but regardless of the
      condensation stage. Model C: GV oocytes were grouped according to the combination
      of both of the previously mentioned parameters (chromatin condensation and
      distribution in relation to the NLB). RESULT(S): According to the GV
      classification of model A, nucleoplasm, nucleus position, nuclear envelope
      continuity, and oocyte size were shown to be relevant and were included in a
      mathematical model for predicting chromatin condensation stage. CONCLUSION(S):
      Noninvasive analysis of GV oocytes using contrast-phase microscopy maintains
      oocytes in a viable state and allows the chromatin condensation status to be
      predicted.

PMID- 19596312
TI  - The acrosomal protein Dickkopf-like 1 (DKKL1) facilitates sperm penetration of
      the zona pellucida.
AB  - OBJECTIVE: To determine the role of Dkkl1 in mouse development, viability, and
      fertility. DESIGN: Prospective experimental study. SETTING: Government research
      institution. ANIMAL(S): Mice of C57BL/6, B6D2F1/J, and 129X1/SvJ strains, as well
      as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the
      studies. INTERVENTION(S): Expression of the Dkkl1 gene was characterized during
      early mouse development, and the effects of Dkkl1 ablation on reproduction and
      fertility were characterized in vitro and in vivo. MAIN OUTCOME MEASURE(S): Dkkl1
      RNA expression was determined by Northern blotting hybridization as well as
      quantitative reverse transcriptase-polymerase chain reaction assays. In vitro
      fertilization assays were used to assess fertility of sperm from male mice
      lacking functional Dkkl1. RESULT(S): Dkkl1 is a gene unique to mammals that is
      expressed primarily in developing spermatocytes and its product localized in the
      acrosome of mature sperm. Here we show that Dkkl1 also is expressed in the
      trophectoderm/placental lineage. Surprisingly, embryos lacking DKKL1 protein
      developed into viable, fertile adults. Nevertheless, the ability of sperm that
      lacked DKKL1 protein to fertilize wild-type eggs was severely compromised in
      vitro. Because this defect could be overcome either by removal of the zona
      pellucida or by the presence of wild-type sperm, Dkkl1, either directly or
      indirectly, facilitates the ability of sperm to penetrate the zona pellucida.
      Penetration of the zona pellucida by Dkkl1(-) sperm was delayed in vivo as well
      as in vitro, but the delay in vivo was compensated by other factors during
      preimplantation development. Accordingly, Dkkl1-/- males offer an in vitro
      fertilization model for identifying factors that may contribute to infertility.
      CONCLUSION(S): DKKL1 is a mammalian-specific, acrosomal protein that strongly
      affects in vitro fertilization, although the effect is attenuated in vivo.

PMID- 19596314
TI  - Soy isoflavones and virus infections.
AB  - Isoflavones and their related flavonoid compounds exert antiviral properties in
      vitro and in vivo against a wide range of viruses. Genistein is, by far, the most
      studied soy isoflavone in this regard, and it has been shown to inhibit the
      infectivity of enveloped or nonenveloped viruses, as well as single-stranded or
      double-stranded RNA or DNA viruses. At concentrations ranging from physiological
      to supraphysiological (3.7-370 muM), flavonoids, including genistein, have been
      shown to reduce the infectivity of a variety of viruses affecting humans and
      animals, including adenovirus, herpes simplex virus, human immunodeficiency
      virus, porcine reproductive and respiratory syndrome virus, and rotavirus.
      Although the biological properties of the flavonoids are well studied, the
      mechanisms of action underlying their antiviral properties have not been fully
      elucidated. Current results suggest a combination of effects on both the virus
      and the host cell. Isoflavones have been reported to affect virus binding, entry,
      replication, viral protein translation and formation of certain virus envelope
      glycoprotein complexes. Isoflavones also affect a variety of host cell signaling
      processes, including induction of gene transcription factors and secretion of
      cytokines. The efficacy of isoflavones and related flavonoids in virus
      infectivity in in vitro bioassays is dependent on the dose, frequency of
      administration and combination of isoflavones used. Despite promising in vitro
      results, there is lack of data confirming the in vivo efficacy of soy
      isoflavones. Thus, investigations using appropriate in vivo virus infectivity
      models to examine pharmacological and especially physiological doses of
      flavonoids are warranted.

PMID- 19596315
TI  - Cryopreservation of mammalian oocytes by using sugars: Intra- and extracellular
      raffinose with small amounts of dimethylsulfoxide yields high cryosurvival,
      fertilization, and development rates.
AB  - Accumulation of intra- and extracellular sugars such as trehalose, glucose, and
      raffinose is central to survival strategies of a variety of organisms coping with
      extreme conditions including freezing and almost complete drying. The objective
      of the present study was to investigate the potential application of intra- and
      extracellular raffinose in combination with low concentrations of
      dimethylsulfoxide (Me(2)SO) to mammalian oocyte cryopreservation. To this end,
      the fertilization and embryonic development of cryopreserved metaphase II (M II)
      mouse oocytes were studied in comparison to unfrozen controls. For
      cryopreservation, M II oocytes were microinjected with 0.1M raffinose, and then
      cooled to -196 degrees C in the presence of either 0.3M raffinose and 0.5M
      Me(2)SO (cryopreservation group 1) or 0.3M raffinose and 1.0M Me(2)SO
      (cryopreservation group 2). The control groups included untreated oocytes
      (untreated control) and oocytes microinjected with raffinose, but not frozen
      (injection control). The post-thaw survival rates were 83.9% and 80.6% for the
      cryopreservation group 1 and 2, respectively. The fertilization and blastocyst
      rates in the cryopreservation group 1 (90.0% and 77.8%, respectively) and 2
      (94.6% and 72.5%, respectively) were also high and similar to the ones of the
      injection controls (97.8% and 78.5%, respectively) and untreated controls (98.8%
      and 83.6%, respectively). These results are consistent with the findings of our
      earlier studies and support the use of sugars as intra- and extracellular
      cryoprotectants. Furthermore, the results of the present study indicate that the
      presence of intra- and extracellular sugars alleviates high concentrations of
      conventional penetrating cryoprotectants, and thus minimizes their toxicity.

PMID- 19596316
TI  - Four score years and ten: an analysis of the epidemiology of fractures in the
      very elderly.
AB  - Fragility fractures are becoming more common and with increasing longevity it
      seems likely that orthopaedic surgeons will see more such fractures in
      progressively older patients. We have examined the epidemiology of fractures in
      patients aged 90 years or more. INTRODUCTION: The purpose of this study was to
      examine the epidemiology of fractures in the very elderly to see if it differed
      from the overall fracture epidemiology. The requirement for hospital admission
      and surgical treatment was assessed as was the patients' domicile, length of
      hospital stay and discharge location. MATERIALS AND METHODS: All fractures
      presenting to the Royal Infirmary of Edinburgh and the Royal Hospital for Sick
      Children in 2000 were examined prospectively and recorded on databases. A
      retrospective examination of the clinical and social details of the 90+ age group
      was undertaken. RESULTS: The 90+ age group comprises 0.58% of the population but
      accounts for 3.02% of the fractures in the community, 8.7% of the in-patient
      admissions and 7.6% of the acute orthopaedic trauma surgery. About 56% of
      fractures in this age group are proximal femoral fractures but high prevalences
      were noted for all femoral fractures. About 65% of the fractures were in the
      lower limb. Over 86% of fractures occurred in falls and over 81% of patients were
      treated as in-patients. The average hospital stay was 9 days but only 23.9% were
      discharged to their domicile. DISCUSSION: It is forecast that this age group will
      increase and become less fit. This has significant implications for hospital
      treatment and costs.

PMID- 19596317
TI  - Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for
      development of the retinal pigment epithelium.
AB  - Wnt/beta-catenin signaling is highly active in the dorsal retinal pigment
      epithelium (RPE) during eye development. To study the role of Wnt/beta-catenin
      signaling in the RPE development we used a conditional Cre/loxP system in mice to
      inactivate or ectopically activate Wnt/beta-catenin signaling in the RPE.
      Inactivation of Wnt/beta-catenin signaling results in transdifferentiation of RPE
      to neural retina (NR) as documented by downregulation of RPE-specific markers
      Mitf and Otx2 and ectopic expression of NR-specific markers Chx10 and Rx,
      respectively. In contrast, ectopic activation of Wnt/beta-catenin signaling
      results in the disruption of the RPE patterning, indicating that precise spatial
      and temporal regulation of Wnt/beta-catenin signaling is required for normal RPE
      development. Using chromatin immunoprecipitation (ChIP) and reporter gene assays
      we provide evidence that Otx2 and RPE-specific isoform of Mitf, Mitf-H, are
      direct transcriptional targets of Wnt/beta-catenin signaling. Combined, our data
      suggest that Wnt/beta-catenin signaling plays an essential role in development of
      RPE by maintaining or inducing expression of Mitf and Otx2.

PMID- 19596318
TI  - Microglia derived IL-6 suppresses neurosphere generation from adult human retinal
      cell suspensions.
AB  - Following retinal degeneration or inflammation that disrupts tissue architecture,
      there is limited evidence of tissue regeneration, despite evidence of cells with
      progenitor properties in the adult human retina at all ages. With the prospect of
      tissue/cell transplantation, redressing homeostasis whilst overcoming glial
      barrier or gliosis remains key to successful graft versus host integration and
      functional recovery. Activated human retinal microglia (MG) secrete cytokines,
      including IL-6, which may suppress neurogenesis or cellular (photoreceptor)
      replacement. To investigate this hypothesis, adult human retinal explants were
      cultured in cytokine-conditioned media (TNFalpha, TGFbeta, LPS/IFNgamma) to
      activate microglia in situ. Following culture of retinal explants for 4 days,
      supernatant conditioned by resulting migrated microglia was collected after a
      further 3 days and fed to retinal cell suspensions (RCS). Neurosphere (NS)
      generation and survival analysis was performed after 7 and 14 days in culture,
      with or without addition of conditioned media and with or without concomitant IL
      6 neutralisation. Neurosphere phenotype was analysed by immunohistochemistry and
      cell morphology. Migratory MG from retinal explants were activated (iNOS
      positive) and expressed CD45, CD11b, and CD11c. LPS/IFNgamma-activated MG
      conditioned media (MG-CM) contained significant levels of IL-6 (1265 +/- 143)
      pg/ml, which inhibited neurosphere generation within RCS in the presence of
      optimal neurosphere generating N2-FGF2 culture medium. Neutralising IL-6 activity
      reinstated NS generation and the differentiation capacity was maintained in the
      spheres that formed. Even in the presence of high levels of IL-6, those few NS
      that did form demonstrated a capacity to differentiate. The data supports
      activated MG-derived IL-6 influence retinal cell turnover.

PMID- 19596319
TI  - Inhibition of corneal neovascularization with plasmid pigment epithelium-derived
      factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18)
      vector in an experimental model of rat corneal angiogenesis.
AB  - The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid
      pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to
      treat corneal neovascularization in a rat model was evaluated. Four partially
      dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p
      PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia
      propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid
      basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was
      prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the
      same side. Inhibition of neovascularization was observed and quantified from day
      1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by
      biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene
      expression in corneal and conjunctival tissue was observed as early as 3 days
      after gene transfer and stably lasted for over 3 months with minimal immune
      reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18
      successfully inhibited corneal neovascularization. Successful gene expression of
      bFGF, PEDF and a mild immune response of HLA-DR were shown by
      immunohistochemistry staining. We concluded that SAINT-18 was capable of directly
      delivering genes to the ocular surface by way of subconjunctival injection, and
      delivered sustained, high levels of gene expression in vivo to inhibit
      angiogenesis.

PMID- 19596320
TI  - High-salt loading exacerbates increased retinal content of aquaporins AQP1 and
      AQP4 in rats with diabetic retinopathy.
AB  - In the neural retina, glial cells control formation of ionic gradients by
      mediating transmembrane water fluxes through aquaporin (AQP) water channels.
      Retinal content and immunolocalization of two water channels, AQP1 and AQP4, in
      the diabetic rat retinas during high-salt loading were examined in this study.
      Diabetes was induced by an intraperitoneal injection of streptozotocin. Diabetic
      and control animals were observed after varying lengths of exposure to normal-
      and high-salt conditions. Ultrathin sections of retinal tissue, stained with
      uranyl acetate and lead citrate, were photographed using a transmission electron
      microscope (TEM). Retinal wholemounts were immunostained with AQP1 and AQP4
      antibody to detect the immunolocalization changes by confocal microscopy. AQP1
      and AQP4 content were evaluated by Western blot analysis. In the retinas of high
      salt loading diabetic animals, obviously increased intracellular edema was
      observed by TEM in ganglion cells and mitochondrial swelling was observed in
      glial cells. Immunolocalization of AQP1 increased from the posterior to
      peripheral retina. Western blot results indicated that a high-salt diet may cause
      increased retinal content of AQP4 and may exacerbate increased retinal content of
      AQP1 caused by diabetic retinopathy. High-salt loading may increase neural
      retinal edema in rats with diabetic retinopathy, and altered glial cell mediated
      water transport via AQP channels in the retina may play an important role in the
      neural retinal edema formation and resolution.

PMID- 19596321
TI  - Rediscovering a history of nursing management: from Nightingale to the modern
      matron.
AB  - OBJECTIVES: This paper presents an examination of distinct periods in the
      development of nursing in order to rediscover a history of nursing management in
      England. The overall purpose is to demonstrate that uncritical accounts written
      in the past have not adequately explained the complex factors that have shaped
      nursing management in England. It is also suggested that the approach taken may
      be usefully applied to other national contexts. DESIGN: This is a review article
      which first establishes the value of historical perspectives in increasing
      understanding of nursing and then goes on to analyse the professional, social and
      political forces that contributed to the development of nursing management. DATA
      SOURCES: A range of historical and contemporary sources is accessed to support
      the review. REVIEW METHODS: The review is informed by an historical approach
      which also seeks recourse to current literature to develop a critical narrative
      analysis which has an international dimension. CONCLUSIONS: The history of
      nursing management has been 'lost' in celebratory and uncritical accounts of
      nursing as a whole. The important influence of key figures other than Nightingale
      has been overlooked and it emerges that nursing management has a longer and more
      complex history than is generally accepted.

PMID- 19596323
TI  - Emotional intelligence and nursing: an integrative literature review.
AB  - AIM: The purpose of this paper is to present findings of an integrative
      literature review related to emotional intelligence (EI) and nursing. BACKGROUND:
      A large body of knowledge related to EI exists outside nursing. EI theory and
      research within nursing is a more recent phenomenon. A broad understanding of the
      nature and direction of theory and research related to EI is crucial to building
      knowledge within this field of inquiry. METHOD: A broad search of computerized
      databases focusing on articles published in English during 1995-2007 was
      completed. Extensive screening sought to determine current literature themes and
      empirical research evidence completed in nursing focused specifically on
      emotional intelligence. RESULTS: 39 articles are included in this integrative
      literature review (theoretical, n=21; editorial, n=5; opinion, n=4 and empirical,
      n=9). The literature focuses on EI and nursing education, EI and nursing
      practice, EI and clinical decision-making, and EI and clinical leadership.
      Research that links EI and nursing are mostly correlation designs using small
      sample sizes. CONCLUSION: This literature reveals widespread support of EI
      concepts in nursing. Theoretical and editorial literature confirms EI concepts
      are central to nursing practice. EI needs to be explicit within nursing education
      as EI might impact the quality of student learning, ethical decision-making,
      critical thinking, evidence and knowledge use in practice. Emotionally
      intelligent leaders influence employee retention, quality of patient care and
      patient outcomes. EI research in nursing requires development and careful
      consideration of criticisms related to EI outside nursing is recommended.

PMID- 19596322
TI  - Using the serious mental illness health improvement profile [HIP] to identify
      physical problems in a cohort of community patients: a pragmatic case series
      evaluation.
AB  - BACKGROUND AND OBJECTIVES: The physical health of people with serious mental
      illness is a cause of growing concern to clinicians. Life expectancy in this
      population may be reduced by up to 25 years and patients often live with
      considerable physical morbidity that can dramatically reduce quality of life and
      contribute to social exclusion. This study sought to determine whether the
      serious mental illness health improvement profile [HIP], facilitated by mental
      health nurses [MHNs], has the clinical potential to identify physical morbidity
      and inform future evidence-based care. DESIGN: Retrospective documentation audit
      and qualitative evaluation of patients' and clinicians' views about the use of
      the HIP in practice. SETTING: A nurse-led outpatient medication management
      clinic, for community adult patients with serious mental illness in Scotland.
      PARTICIPANTS: 31 Community patients with serious mental illness seen in the
      clinic by 2 MHNs trained to use the HIP. All 31 patients, 9 MHNs, 4 consultant
      psychiatrists and 12 general practitioners [GPs] (primary care physicians)
      participated in the qualitative evaluation. METHODS: A retrospective
      documentation audit of case notes for all patients where the HIP had been
      implemented. Semi-structured interviews with patients and their secondary care
      clinicians. Postal survey of GPs. RESULTS: 189 Physical health issues were
      identified (mean 6.1 per patient). Items most frequently flagged 'red',
      suggesting that intervention was required, were body mass index [BMI] (n=24),
      breast self-examination (n=23), waist circumference (n=21), pulse (n=14) and diet
      (n=13). Some rates of physical health problems observed were broadly similar to
      those reported in studies of patients receiving antipsychotics in primary care
      but much lower than those reported in epidemiological studies. Individualised
      care was planned and delivered with each patient based on the profile. 28
      discreet interventions that included providing advice, promoting health
      behavioural change, performing an electrocardiogram and making a referral to
      professional colleagues were used. Qualitative feedback was positive. Our
      observations support the use of the HIP in clinical settings to enhance mental
      health nursing practice; however, we strongly recommend that training is required
      to support the use of the HIP.

PMID- 19596325
TI  - To whom are we writing?

PMID- 19596324
TI  - The relationship between job stressors, hardy personality, coping resources and
      burnout in a sample of nurses: a correlational study at two time points.
AB  - BACKGROUND: Nursing is considered as a risk profession with high levels of stress
      and burnout, and these levels are probably increasing. OBJECTIVES: This study
      assessed temporal and cross-sectional relationships between job stressors, hardy
      personality and coping resources on burnout dimensions among nurses. DESIGN:
      Temporal and cross-sectional effects were evaluated. A sample of 98 nurses from
      Portugal completed the Nursing Burnout Scale at two time points. The data were
      analysed using descriptive statistics, Pearson correlations, and hierarchical
      linear regression analyses regressing Wave 2 burnout dimensions. RESULTS: The
      study confirmed the specific contribution of control and challenged hardy
      personality dimensions as the explanation of burnout. However, commitment did not
      show any effects in this study. Social support and active coping were also
      relevant predictors of burnout dimensions. Specifically, active coping had an
      inverse temporal effect on depersonalisation and lack of personal accomplishment.
      In relation to the burnout process, depersonalisation appeared as an antecedent
      of lack of personal accomplishment. CONCLUSIONS: The present study is an initial
      step to comprehend the link between job stressors, hardy personality, coping
      resources and diminishing burnout.

PMID- 19596326
TI  - Cell-scaffold mechanical interplay within engineered tissue.
AB  - Effective tissue engineering requires appropriate selection of cells and
      scaffold, where the latter serves as a mechanical and biological support for cell
      growth and functionality. The optimal combination of cell source and scaffold
      properties can vary for each desired application. Such preconditions necessitate
      enhanced understanding of the interactions between cells and scaffold within
      engineered tissue. Several studies have examined the deforming effects cells
      induce in scaffolds via exertion of contractile forces. In contrast, other
      studies focus on the scaffold's biochemical and mechanical properties and their
      effects on cell behavior. This review summarizes the mechanical interplay between
      cells and scaffold within engineered tissue. We present evidence for contractile
      forces exerted by cells on three-dimensional (3D) scaffolds and discuss existing
      methods for their quantification. In addition, we address some theories related
      to the effects of scaffold stiffness and mechanical stimulation on cell behavior.
      Further understanding of the reciprocal effects between cells and scaffold will
      provide both enhanced knowledge regarding the expected properties of engineered
      tissue and more competent tissue regeneration techniques.

PMID- 19596327
TI  - The role of Fgf8 in telencephalic and diencephalic patterning.
AB  - Correct patterning of the developing brain is crucial importance for accurate
      wiring and function. Although the adult brain contains many complex structures,
      it begins with a simple structure-the neural tube. As it develops, the neural
      tube is divided into several regions, including the telencephalon, diencephalon,
      midbrain, and hindbrain. In each of these regions, signaling molecules are
      secreted from discrete zones, which establish positional information and regulate
      regional growth. There are many mechanistic questions that remain to be resolved
      about the action of these growth and differentiation factors. The cellular
      factors mediating patterning in response to these factors are largely unknown.
      Furthermore, identical differentiation factors are expressed in different regions
      of the brain and yet control significantly different patterning mechanisms, and
      the factors that control region-specific responses to these factors are mostly
      obscure. Furthermore, differentiation factors also show dramatically different
      expression patterns in different vertebrate species that may underlie changes in
      brain structure, but the mechanisms by which these changes in gene expression
      occur poorly understood. To address these issues, we discuss the role of Fgf8,
      which controls anterior/posterior patterning in different regions of the
      developing brain. We also discuss how modifications of Fgf8 expression in the
      diencephalon controlled by retrotransposons can change the shape and function of
      the brain in various species.

PMID- 19596329
TI  - Genetic variation in the ABCA1 gene, HDL cholesterol, and risk of ischemic heart
      disease in the general population.
AB  - Epidemiological studies consistently demonstrate a strong inverse association
      between low levels of high-density lipoprotein (HDL) cholesterol and increased
      risk of ischemic heart disease (IHD). This review focuses on whether both rare
      and common genetic variation in ABCA1 contributes to plasma levels of HDL
      cholesterol and to risk of IHD in the general population, and further seeks to
      understand whether low levels of HDL cholesterol per se are causally related to
      IHD. Studies of the ABCA1 gene demonstrate a general strategy for detecting
      functional genetic variants, and show that both common and rare ABCA1 variants
      contribute to levels of HDL cholesterol and risk of IHD in the general
      population. The association between ABCA1 variants and risk of IHD appears,
      however, to be independent of plasma levels of HDL cholesterol. With the recent
      identification of the largest number of individuals heterozygous for loss-of
      function mutations in ABCA1 worldwide, population studies suggests that
      genetically low HDL cholesterol per se does not predict an increased risk of IHD,
      and thus questions the causality of isolated low levels of HDL cholesterol for
      the development of IHD.

PMID- 19596328
TI  - Epithelial IgG and its relationship to the loss of F508 in the common mutant form
      of the cystic fibrosis transmembrane conductance regulator.
AB  - The most debilitating feature of cystic fibrosis (CF) disease is uncontrolled
      inflammation of respiratory epithelium. The relationship between the commonest
      mutated form of CFTR (F508del or DeltaF508) and inflammation has not yet been
      elucidated. Here, we present a new paradigm suggesting that CFTR can interact
      with intra-epithelial IgG, establishing a direct link between normal CFTR and the
      immune system. Further, our data show that the amino-acid sequence local to F508
      can bind IgG with high affinity, dependent on F508, such that loss of F508
      abolishes this link both in vitro and in the intact cell.

PMID- 19596330
TI  - Associations of genetic polymorphisms of arachidonate 5-lipoxygenase-activating
      protein with risk of coronary artery disease in a European-American population.
AB  - OBJECTIVE: To examine whether genetic polymorphisms in the 5-lipoxygenase
      activating protein (ALOX5AP) confer an increased risk to angiographically proven
      coronary artery disease (CAD) in a case-control study of a Midwestern population
      in the US. METHODS: We genotyped 7 SNPs (SG13S25, SG13S89, SG13S41, SG13S377,
      SG13S35, SG13S114, and SG13S32) in the ALOX5AP gene in 500 angiographically
      proven coronary artery disease (CAD) cases and 500 age- and gender-matched
      controls of European-American ancestry living in upper-Midwest US. Genotypes were
      determined using a multiplexing application of SEQUENOM methodology for
      homogenous MassEXTEND assay. Two haplotypes (HapA and HapB) that were previously
      identified to be associated with the risk of myocardial infarction (MI) in the
      Icelandic or British populations of the original deCODE study were analyzed along
      with individual SNPs. RESULTS: HapB was significantly associated with the risk of
      premature CAD, independent of the influence of age, gender, total and HDL
      cholesterol (ORs of 2.06 without covariate adjustment; 2.05 after multivariable
      adjustment). SNP SG13S377, one of the SNPs used to define HapB, was also
      independently and significantly associated with the risk of premature CAD.
      CONCLUSION: Our study suggests a significant but modest contribution of the
      ALOX5AP gene variants to the susceptibility of premature CAD in an US Midwestern
      population of European-American ancestry.

PMID- 19596332
TI  - Stress and fish reproduction: the roles of allostasis and hormesis.
AB  - This paper is a review of the effects of stress on reproduction in fishes. I hope
      to further the development of the concepts of allostasis and hormesis as relevant
      to understanding reproduction in general and in fish in particular. The main
      contentions I derive in this review are the following: Stressors affect fish
      reproduction in a variety of ways depending on the nature and severity of the
      stressor. The effects are transduced through a hormonal cascade initiated by
      perception of the stressor and involving the hypothalamus-pituitary-interrenal
      axis, the catecholamines, and also cytokines. Mounting a stress response and
      resisting a stressor is an energetically costly process, including costs
      associated with allostasis, attempting to reset homeostatic norms. Responses in
      emergency situations (e.g., being chased by a predator or a net) can be different
      from those where fish can cope (e.g., being in a more crowded environment) with a
      stressor, but both situations involve energy re-budgeting. Emergency responses
      happen in concert with the onset of energy limitations (e.g., the fish may not
      eat), while coping with allostatic overload can happen in a more energy-rich
      environment (e.g., the fish can continue to eat). Low levels of stress may have a
      positive effect on reproductive processes while greater stress has negative
      effects on fish reproduction. The concept of hormesis is a useful way to think
      about the effect of stressors on fish reproduction since responses can be
      nonmonotonal, often biphasic.

PMID- 19596331
TI  - Comparison of predictive ability of lipoprotein components to that of traditional
      risk factors of coronary events in renal transplant recipients.
AB  - OBJECTIVE: Risk factors for major adverse coronary events (MACE) in renal
      transplant recipients are often different from those of non-transplanted
      populations. We compared the predictive power of lipoprotein components (LC) to
      that of more traditional risk factors such as serum creatinine, diabetes and
      inflammation measured by C-reactive protein (CRP) in the assessment of lescol in
      renal transplantation (ALERT) trial population. METHODS: From the 2102 randomized
      patients in ALERT we selected 1734 patients with a complete set of risk and
      adjustment factors used in the study. Cox regression analysis was used to
      estimate relationships between baseline values of risk factors and first
      occurrence of MACE. Chi square statistics, receiver operating characteristics
      (ROC) and net reclassification improvement (NRI) were used to compare the
      information value of different risk factors. RESULTS: Atherogenic LC and
      especially non-high density cholesterol (nHDL-C) were as predictive as creatinine
      and nHDL-C was about as predictive as diabetes. CRP, body mass index,
      hypertension and glucose had less prediction ability than nHDL-C. The rank order
      of prediction was the same in the two treatment groups. By regression modelling
      the actual MACE risk reduction from 6 weeks onwards was well predicted from the
      difference in LC at 6 week. CONCLUSION: LC and especially nHDL-C predicted MACE
      at least as good as creatinine. Diabetes was about equally good as nHDL-C to
      predict MACE occurrence. Inflammation had less prediction ability than the other
      factors. Treated levels of atherogenic LC predicted MACE risk reduction well.

PMID- 19596333
TI  - Enhanced resolution comprehensive two-dimensional gas chromatography applied to
      the analysis of roasted coffee volatiles.
AB  - The present research is based on the full exploitation of the separation power of
      a 0.05 mm internal diameter (ID) capillary, as a comprehensive two-dimensional
      (2D) GC (GC x GC) secondary column, with the objective of attaining very high
      resolution second dimension separations. The aim was achieved by using a split
      flow system developed in previous research [P.Q. Tranchida, A. Casilli, P. Dugo,
      G. Dugo, L. Mondello, Anal. Chem. 79 (2007) 2266], and a dual-oven GC x GC
      instrument. The column combination employed consisted of a polar 30 m x 0.25 mm
      ID column connected, by means of a T union, to a detector-linked high-resolution
      1.1 m x 0.05 mm ID apolar analytical column and to a 0.33 m x 0.05 mm ID
      retention gap; the latter was connected to a manually operated split valve. As
      previously demonstrated, the use of a split valve enables the regulation of gas
      flows through both analytical columns, generating the most appropriate gas linear
      velocities. Comprehensive 2D GC experiments were carried out on Arabica roasted
      coffee volatiles (previously extracted by means of solid-phase microextraction)
      with the split-valve closed (equal to what can be defined as conventional GC x
      GC) and with the split-valve opened at various degrees. The reasons why it is
      absolutely not effective to use a 0.05 mm ID column as second dimension in a
      conventional GC x GC instrument will be discussed and demonstrated. On the
      contrary, the use of a 0.05 mm ID column as second dimension, under ideal
      conditions in a split-flow, twin-oven system, will also be illustrated and
      discussed.

PMID- 19596334
TI  - Entomopathogenic fungi recorded from the harlequin ladybird, Harmonia axyridis.
AB  - Entomopathogenic fungi were recorded from field samples of the harlequin ladybird
      Harmonia axyridis, an invasive coccinellid that has recently arrived in Denmark.
      Larvae, pupae and adults were found to be infected by Isaria farinosa, Beauveria
      bassiana and species of Lecanicillium. This is the first record of
      entomopathogenic fungi infecting larvae and pupae. Winter mortality due to fungal
      infection reached 17.9% in adults collected at one location. The larval stage was
      most susceptible to fungal infection, as confirmed through bioassay with I.
      farinosa.

PMID- 19596335
TI  - A general, accurate procedure for calculating molecular interaction force.
AB  - The determination of molecular interaction forces, e.g., van der Waals force,
      between macroscopic bodies is of fundamental importance for understanding
      sintering, adhesion and fracture processes. In this paper, we develop an
      accurate, general procedure for van der Waals force calculation. This approach
      extends a surface formulation that converts a six-dimensional (6D) volume
      integral into a 4D surface integral for the force calculation. It uses non
      uniform rational B-spline (NURBS) surfaces to represent object surfaces. Surface
      integrals are then done on the parametric domain of the NURBS surfaces. It has
      combined advantages of NURBS surface representation and surface formulation,
      including (1) molecular interactions between arbitrary-shaped objects can be
      represented and evaluated by the NURBS model further common geometries such as
      spheres, cones, planes can be represented exactly and interaction forces are thus
      calculated accurately; (2) calculation efficiency is improved by converting the
      volume integral to the surface integral. This approach is implemented and
      validated via its comparison with analytical solutions for simple geometries.
      Calculation of van der Waals force between complex geometries with surface
      roughness is also demonstrated. A tutorial on the NURBS approach is given in
      Appendix A.

PMID- 19596336
TI  - On the pinning of interfaces on micropillar edges.
AB  - Microsystems for biotechnology often make use of pillars to perform the targeted
      microfluidic functions. In many cases the role of the pillars is to block or
      maintain fixed an interface between two immiscible fluids. This phenomenon is
      usually called pinning. The pining principle is used for capillary valves, liquid
      liquid extraction devices, etc. It is common to estimate the pinning efficiency
      by considering mathematically perfect edges. In reality, microfabricated edges
      always show some smoothness that can be modeled by a small curvature radius. In
      this work, we investigate the pinning on square, circular, triangular, and
      diamond-shaped pillars, and analyze the anchoring on the upstream edges (first
      pinning conditions) and possibly on the downstream edges (second pinning
      conditions). It is shown that pinning efficiency decreases very quickly with the
      curvature radius of the pillar edge. It is concluded that the quality of the
      microfabrication is essential. Especially oxidation of the silicon reduces
      considerably the pinning efficiency. Moreover, it is shown that square pillars
      pin better an interface than triangular pillars. For triangular pillars, a pillar
      angle--angle between two facets--optimal for pinning has been determined that
      depends on the quality of microfabrication.

PMID- 19596337
TI  - Nonlinear electrokinetic phenomena around nearly insulated sharp tips in
      microflows.
AB  - This contribution seeks to provide for the first time a combined comprehensive
      theoretical prediction and quantitative experimental (microparticle imaging
      velocimetry--micro-PIV) measurements of the nonlinear electrokinetic flow around
      sharp tips in order to substantiate former theoretical and qualitative
      experimental flow visualization results [S.K. Thamida, H.C Chang, Phys. Fluids 14
      (2002) 12; P. Takhistov, K. Duginova, H.C. Chang, J. Colloid Interface Sci. 263
      (2003) 133; G. Yossifon, I. Frankel, T. Miloh, Phys. Fluids 18 (2006) 117108].
      The study focuses on two microchannel designs: an L-shaped channel and two
      isolated tips in a straight channel, important in engineering for mixing and
      particle-trapping purposes. The new experimental results were explained in terms
      of an induced-charge electrokinetic mechanism alone, without the concentration
      polarization mechanism as suggested by earlier studies. The vortex generation
      phenomenon around corners was explained in terms of the varying ratio between the
      equilibrium and the induced-charge zeta-potentials, showing fair qualitative
      agreement between numerical and experimental results. Hence, a transition from an
      irrotational to nonlinear-dominated flow with a vortex pattern occurs beyond a
      certain electric-field threshold. In particular, for the L-shaped channel case,
      it is demonstrated that beyond a second field threshold an upstream vortex
      appears in addition to the downstream one.

PMID- 19596338
TI  - Probing the interaction of the amino acid alanine with the surface of ZnO(1010).
AB  - The adsorption modes and stability of the amino acid alanine (NH(2)-CH(CH(3))
      COOH) have been studied on the nonpolar single crystal surface of zinc oxide,
      ZnO(1010), experimentally by X-ray photoelectron spectroscopy (XPS) and
      computationally using density functional theory (DFT). Deposition at 200 K was
      found to lead to the formation of multilayers identified by an XPS N1s peak at
      401.7 eV assigned to the NH(3)(+) group, a fingerprint of the zwitterionic
      structure of alanine in the solid state. Heating to 300 K resulted in the removal
      of most of the multilayers with the remaining surface coverage estimated to 0.4
      with respect to Zn cations. At this temperature most of the alanine molecules are
      found to be deprotonated (dissociated), yielding a carboxylate species (NH(2)
      CH(CH(3))-COO(-) (a) + OH (s); where O is surface oxygen, (a) for adsorbed and
      (s) for surface species). Further heating of the surface resulted in a gradual
      decrease of the surface coverage and by 500 K a large fraction of adsorbed
      alanine molecules have desorbed from the surface. Total energy DFT computations
      of different adsorbate species identified two stable dissociative adsorption
      modes: bidentate and monodentate. The bidentate species with adsorption energy of
      1.75 eV was found to be more stable than the monodentate species by about 0.7 eV.

PMID- 19596339
TI  - Refinement of protein structures into low-resolution density maps using rosetta.
AB  - We describe a method based on Rosetta structure refinement for generating high
      resolution, all-atom protein models from electron cryomicroscopy density maps. A
      local measure of the fit of a model to the density is used to directly guide
      structure refinement and to identify regions incompatible with the density that
      are then targeted for extensive rebuilding. Over a range of test cases using both
      simulated and experimentally generated data, the method consistently increases
      the accuracy of starting models generated either by comparative modeling or by
      hand-tracing the density. The method can achieve near-atomic resolution starting
      from density maps at 4-6 A resolution.

PMID- 19596341
TI  - [From clinical observation to assessment of practices. Proceedings of Hemotech
      Symposium, Nancy, France, October 16-17, 2008].

PMID- 19596342
TI  - [From clinical observation to assessment of practices: guidelines for
      hypertension management].
AB  - Arterial hypertension is highly prevalent and one of the main risk factors for
      cardiovascular diseases. It has been demonstrated that antihypertensive treatment
      is effective to prevent cardiovascular events. Advances have been made in this
      field for 50 years and the knowledge and management of hypertension has been
      modified continuously with increase of related costs. Therefore hypertension is
      one of the favorite themes for guidelines and indeed several guidelines have been
      published on this theme regularly. Despite this, a high percentage of treated
      hypertensive patients remains uncontrolled. Several reasons have been raised for
      not implementing guidelines: these guidelines are often little-known because of
      their large number and their bad distribution. A systematic analysis of the last
      guidelines showed also they were structurally different with a small percentage
      of identical references and they provided sometimes different practical
      conclusions. Finally, clinical inertia is partly responsible for these
      insufficient results. As the current form of the guidelines has a limited impact
      on the medical practice, we should find other methods to improve their
      implementation.

PMID- 19596340
TI  - E. coli transports aggregated proteins to the poles by a specific and energy
      dependent process.
AB  - Aggregation of proteins due to failure of quality control mechanisms is
      deleterious to both eukaryotes and prokaryotes. We found that in Escherichia
      coli, protein aggregates are delivered to the pole and form a large polar
      aggregate (LPA). The formation of LPAs involves two steps: the formation of
      multiple small aggregates and the delivery of these aggregates to the pole to
      form an LPA. Formation of randomly distributed aggregates, their delivery to the
      poles, and LPA formation are all energy-dependent processes. The latter steps
      require the proton motive force, activities of the DnaK and DnaJ chaperones, and
      MreB. About 90 min after their formation, the LPAs are dissolved in a process
      that is dependent upon ClpB, DnaK, and energy. Our results confirm and
      substantiate the notion that the formation of LPAs allows asymmetric inheritance
      of the aggregated proteins to a small number of daughter cells, enabling their
      rapid elimination from most of the bacterial population. Moreover, the results
      show that the processing of aggregated proteins by the protein quality control
      system is a multi-step process with distinct spatial and temporal controls.

PMID- 19596343
TI  - [Knowledge transfer and implementation of clinical practice guidelines.
      Experience of the Canadian Hypertension Education Program].
AB  - For the last 10 years, the update of guidelines for the treatment of hypertension
      in Canada is part of an annual process. This national strategy called the
      Canadian Hypertension Education Program (CHEP) has an organizational structure
      which allows not only to revise guidelines using an evidence-based scientific
      process but also to facilitate the implementation and the dissemination of the
      recommendations to the various healthcare professionals (doctors, pharmacists,
      nurses, etc.). As part of this process, the CHEP is also measuring different
      outcomes which could estimate the impact of its interventions. Recent data
      clearly show an improvement of the screening of hypertension as well as the
      quality of antihypertensive treatment (increase in the number of new
      prescriptions and of the percentage of subjects treated with 2 antihypertensive
      agents or more) in Canada. Finally, recent Canadian data showing a reduction of
      the cardiovascular complications attributable to hypertension suggest a possible
      link of causality with the implementation of the CHEP. This article will describe
      the functioning of the CHEP with its various strategies aiming at a better
      management of hypertension in Canada.

PMID- 19596344
TI  - [Incidence of chronic kidney disease in general population, EPIRAN study].
AB  - AIMS: To assess incidence of chronic kidney disease in general population and to
      describe baseline characteristics of incident patients. METHODS: Between
      1st/01/04 and 30/06/06 all incident cases of chronic kidney disease in the Nancy
      district were prospectively identified. New cases were identified from all
      medical laboratories in this area and determined by a persistently increased
      serum creatinine level (> or = 150micromol/l, or paediatric levels) for 3 months
      after the 1st/01/04, and by living in Nancy area. RESULTS: The annual incidence
      rate of detected chronic kidney disease was 1 per thousand inhabitants (1,3 per
      thousand for men and 0,7 per thousand for women). Incidents patients were old
      (mean age: 77 years) and with numerous comorbidities (diabetes: 34 %, cardiac
      failure: 23 %). More than 30% of incident patients were diagnosed at sever stage
      of chronic kidney disease (<30ml/min/1,73m(2)). CONCLUSIONS: The annual incidence
      of diagnosed chronic kidney disease is common: 10 times more than end-stage renal
      disease in France. Most of these patients are diagnosed in a severe stage of
      chronic kidney disease whereas they could be detected earlier and benefit from
      adequate, appropriate and multidisciplinary take care.

PMID- 19596345
TI  - [Economic evaluation of health networks: why and how?].
AB  - Although economic evaluation of health networks is part of the legal obligations
      that have to be met since March 2007, its contours still have to be defined. The
      purpose of this paper is to present the reasons for and approaches to such an
      economic analysis. Lessons will also be drawn from two economic evaluations
      carried out in other areas than health networks (respectively, task delegation
      between health care professionals and the assessment of added value for health
      care technologies).

PMID- 19596346
TI  - [Vancomycin resistant Enterococci (VRE)].
AB  - Vancomycin resistant enteroccoci (VRE) has recently emerged in France and in
      Europe whereas it has been endemic in the United States for two decades. Despite
      its little pathogenicity, VRE may be responsible for severe, difficult to treat
      infections in immunocompromised host. Intestinal colonization precedes infection
      and is responsible for VRE silent dissemination. In case of epidemy, infection
      control measures should be quickly implemented to avoid endemicity.

PMID- 19596347
TI  - [Interventions implemented to control an outbreak of vancomycin-resistant
      enterococci in a university hospital].
AB  - At the end of 2004, a Vancomycin-resistant enterococci (VRE) outbreak occurred in
      the university hospital of Nancy. Interventions were simultaneous implemented in
      this hospital (promotion of hand washing, gathering of VRE carriers in the same
      part of units) and the outbreak seemed to be controlled before the end of 2005.
      But one year later, the number of discovered new colonisations increased again.
      Then, promotion of exclusive hand disinfection with alcohol-based hand-rub
      solutions and cohorting of VRE carriers in a dedicate ward were the only two
      effective interventions to control the outbreak. At the beginning of the year
      2007, before being controlled, this outbreak expanded to several other healthcare
      centres in Lorraine. A specific regional team was set up in July 2007. A
      programme to eradicate VRE was elaborated based on national guidelines modified
      and adapted regarding particularities of each situation. These new guidelines
      were published on an internet site. A list of all healthcare centres
      accommodating patients colonized with VRE is established weekly and diffused to
      all hospitals in Lorraine which then could optimise readmission conditions of
      potential VRE carriers or contact patients. Between 2004 and 2008, more than 900
      patients were found colonized with VRE in Lorraine. Finally, the application of
      all the measures previously described, seemed to be efficient to control the ERV
      outbreak in Lorraine.

PMID- 19596349
TI  - [French 2008 guidelines on peritoneal dialysis: indications and non-indications].
AB  - The new French guidelines on Peritoneal Dialysis (PD) were published in october
      2008 by the "Haute Autorite de Sante (HAS)". The field of these guidelines
      concerned the choice between PD and Hemodialysis (HD), on a strict medical point
      of view. This paper summarizes the main French PD guidelines, highlighting the
      new insights compared to previous guidelines. For the first time, guidelines
      described 5 clinical situations requiring the choice between PD or HD : 1)
      criteria for choosing PD in a new dialysis patient ; 2) criteria for switching a
      patient from PD to HD ; 3) criteria for switching a patient from HD to PD ; 4) PD
      or HD before kidney transplantation ; 5) PD or HD after graft failure. For a new
      dialysis patient, PD is recommended, more than HD, for cirrhotic patients with
      ascites, kidney failure due to cholesterol embolism, difficulties for HD-vascular
      access. PD is not recommended in only a few cases : morbid obesity (BMI>45 kg
      /m(2)), irreparable abdominal hernias. It is recommended to switch from PD to HD,
      patients with more than 3 peritonitis/year, due to digestive bacteria ; weight
      gain > 15 % per year ; triglycerid serum level > 10 g/l ; loss of peritoneal
      efficiency. It is recommended to switch from HD to PD patients with vascular
      access failure ; hemodynamic instability during HD sessions ; severe congestive
      heart failure. PD or HD can be indistinctly used before kidney or combined
      pancreas-kidney graft. These new French guidelines are more complete and more
      accurate than the previous French or international guidelines.

PMID- 19596348
TI  - [Control measures for a VRE outbreak in a haemodialysis unit].
AB  - We report an outbreak of colonization with Vancomycin Resistant Enterococci (VRE)
      in the Haemodialysis unit of our hospital. From October 2004 to September 2008,
      19 patients were found positive. The risk of acquiring this multi-resistant
      bacterium is extremely important in patients undergoing haemodialysis, heightened
      measures have gradually been set to control cross transmissions: first isolation,
      then geographic clustering of carriers and finally creating cohorting sectors
      with different staff for carriers, contacts and VRE free patients. This re
      organization was supplemented by strengthening procedures for hand hygiene,
      active screening of patients and enhanced cleaning. Monitoring of the epidemic
      curve has allowed us to demonstrate the effectiveness of measures introduced.
      However, deleterious effects were observed in patients whose habits were changed;
      we could also highlight significant impact on the activity of the unit.

PMID- 19596350
TI  - [Medical and economic evaluation of new peritoneal dialysis solutions].
AB  - Conventional peritoneal dialysis solutions are mostly bioincompatible in
      relationship with a low pH, a high glucose and glucose degradation products (GDP)
      concentrations inducing anatomical and functional peritoneal membrane
      alterations. Use of icodextrin solution instead of glucose hypertonic solution
      preserves peritoneal membrane minimizing glucose exposure and its peritoneal
      absorption. Physiological fluids with a neutral pH and less GDP seem to have a
      positive effect on residual renal function which declines more slowly when they
      are early prescribed, before highly damaged and sclerotic kidneys. Preliminary
      data show that patients and technique survivals are better when physiological
      solutions are used either for diabetic and non diabetic patients. However, these
      new solutions do not improve peritonitis rates except for bicarbonate solutions
      but this fact must still be confirmed by other studies. In spite of a higher
      cost, physiological solutions must be proposed mainly for patients with a low
      comorbidity index and a high life expectancy.

PMID- 19596351
TI  - [Financial barriers and peritoneal dialysis].
AB  - Peritoneal Dialysis (PD) has shown good result for the patients'survival and
      quality of life, but there is no development of PD in France. Many reasons can
      explain this situation, but we will focus here on financial restraint. PD has a
      low reimbursement rate, lower than the real cost of the technique. Furthermore,
      it is very difficult to find a place for PD patients when they need an
      hospitalization or lose their autonomy. The Pilot Committee for Kidney Disease is
      about to propose some solutions, but the effects may be limited as long as the
      difference in the reimbursement rate between PD and in center dialysis will
      persist.

PMID- 19596352
TI  - [Medical care of chronic kidney disease after kidney transplantation].
AB  - Kidney transplantation is the treatment of choice to enhance survival, morbidity
      and quality of life perceived by the patient. Despite improvements in short-term
      outcomes, a gap persists comparing with health of general population. A stringent
      collaboration between the family physician, the community nephrologists, the
      transplant center and others specialists is required. Recent recommendations have
      been published in France.

PMID- 19596353
TI  - [New faces of acute rejection in 2008].
AB  - Along the time, the definition of acute rejection has been modified according to
      the successive Banff classifications, the use of C4d and the identification of
      anti- HLA antibodies. Both cellular and humoral acute rejection are nowadays
      considered to be different with regard to definition, pathogenesis and hence
      treatment. The Banffclassification remains a very useful tool to improve the
      precision of these definitions. The new technologies such as microarrays should
      help to identify new aspects of acute rejection.

PMID- 19596354
TI  - [What tests are necessary before registration on the kidney transplant waiting
      list?].
AB  - Before registering a patient on the kidney transplant waiting list, the medical
      file should be carefully studied looking for factors that may complicate the
      transplantation. Knowledge of the patient's history and the clinical examination
      will guide the choice of complementary examinations. The objectives of
      pretransplantation explorations are : 1) preventing graft rejection ; 2) ensuring
      that arterial and venous anastomoses are possible ; 3) ensuring that urine can be
      drained ; 4) preventing post-transplantation infections ; 5) not performing a
      transplantation on a subject with cancer ; and 6) avoiding any post
      transplantation cardiovascular events. The list of the necessary explorations for
      renal transplantation should be as simple as possible so that registration on the
      transplant waiting list is not delayed, while being as complete as possible to
      prevent any complications that may compromise the results. It should be
      individualized to each patient.

PMID- 19596355
TI  - Ferritin heavy chain (FHC) is up-regulated in papillomavirus-associated
      urothelial tumours of the urinary bladder in cattle.
AB  - The up-regulation of ferritin heavy chain (FHC) is reported in six papillary and
      in four invasive urothelial tumours of the urinary bladder of cattle grazing on
      mountain pastures rich in bracken fern. All tumours contained sequence of bovine
      papillomavirus type-2 (BPV-2) as determined by polymerase chain reaction (PCR)
      analyses and validated by direct sequencing of the amplified products. The
      oncoprotein E5 was also detected in these tumours by immunoprecipitation and by
      immunofluorescence and laser scanning confocal microscopy. Expression of FHC was
      evaluated by western blot analysis, reverse transcriptase (RT) PCR, real-time RT
      PCR and immunohistochemistry. The oligonucleotide sequence of the bovine ferritin
      amplicons was identical to that of human ferritin. Nuclear overexpression of p65,
      an important component of nuclear factor kappaB (NF-kappaB) transcription
      factors, was also observed. These findings suggest that FHC up-regulation may be
      mediated by activation of NF-kappaB and that in turn this may be related to the
      resistance of bovine papillomavirus type-2 (BPV-2) infected urothelial cells to
      apoptosis.

PMID- 19596356
TI  - A mathematical model for pattern formation of glioma cells outside the tumor
      spheroid core.
AB  - Glioblastoma is the most common and the most aggressive type of brain cancer. The
      median survival time from the time of diagnosis is approximately one year.
      Invasion of glioma cells from the core tumor into the surrounding brain tissue is
      a major reason for treatment failure: these migrating cells are not eliminated in
      surgical resection and cause tumor recurrence. Variations are seen in number of
      invading cells, and in the extent and patterns of migration. Cells can migrate
      diffusely and can also be seen as clusters of cells distinct from the main tumor
      mass. This kind of clustering is also evident in vitro using 3D spheroid models
      of glioma invasion. This has been reported for U87 cells stably expressing the
      constitutively active EGFRVIII mutant receptor, often seen expressed in
      glioblastoma. In this case the cells migrate as clusters rather than as single
      cells migrating in a radial pattern seen in control wild type U87 cells. Several
      models have been suggested to explain the different modes of migration, but none
      of them, so far, has explored the important role of cell-cell adhesion. The
      present paper develops a mathematical model which includes the role of adhesion
      and provides an explanation for the various patterns of cell migration. It is
      shown that, depending on adhesion, haptotactic, and chemotactic parameters, the
      migration patterns exhibit a gradual shift from branching to dispersion, as has
      been reported experimentally.

PMID- 19596357
TI  - The EGFR inhibitor gefitinib suppresses recruitment of pericytes and bone marrow
      derived perivascular cells into tumor vessels.
AB  - Drugs that target EGFR have established anti-tumor effect and are used in the
      clinic. Here we addressed whether inhibition of EGFR tyrosine kinase activity by
      gefitinib in tumor microenvironment affected tumor angiogenesis or
      vasculogenesis. A syngeneic tumor model of mice with grafted GFP-labeled bone
      marrow cells was used to analyze the effects of gefitinib on different cellular
      components of tumor vasculature. To characterize tumor cell-independent stromal
      effects of EGFR targeting, the mice were injected with B16 melanoma cells not
      expressing significant quantities of EGFR, and treated with gefitinib for seven
      days, a period not sufficient for significant reduction in total tumor volume.
      Numbers of vessels as well as cell surface areas covered by markers of
      endothelial, pericyte and bone marrow-derived progenitor cells were quantified by
      image analysis of tumor sections. Quantitative analysis of immunohistochemical
      data demonstrated that gefitinib decreased the coverage of small CD31-positive
      vessels with NG2-positive pericytes, as well as reduced the recruitment of
      perivascular GFP-positive bone marrow-derived progenitor cells within the tumor
      tissue. These results suggest that inhibition of EGFR activity in tumors has
      vascular effects in the absence of direct effect on tumor cells. EGFR targeting
      may lead to suppressed mobilization of pericytes needed for vessel stabilization,
      as well as of bone marrow-derived perivascular progenitor cells. These findings
      introduce novel cellular mechanisms by which EGFR targeted drugs may suppress
      tumor growth.

PMID- 19596358
TI  - The acute and subchronic effects of a brain-penetrating, neurotensin-1 receptor
      agonist on feeding, body weight and temperature.
AB  - The neurotensin-1 (NT1) receptor has been implicated in mediating a number of
      important neurotensin effects. We have found that PD149163, a selective, brain
      penetrating, NT1 receptor agonist, produces a number of therapeutic-like
      preclinical effects after peripheral administration including pro-cognitive,
      antipsychotic and anxiolytic effects. In this study, we investigated PD149163's
      effect on food intake and thermal regulation, two physiological processes thought
      to be mediated by NT1 receptors. Brown Norway rats and leptin-deficient mice
      (ob/ob) mice were administered subcutaneous PD149163 (0, 0.1, 0.25, or 1 mg/kg)
      for ten consecutive days. Weight and 24-h food intake were measured in mice and
      rats and core body temperature was also measured in rats. PD149163 significantly
      decreased food intake in rats and ob/ob mice and no tolerance was demonstrated to
      this effect over the course of the study. PD149163-treated animals exhibited
      weight loss compared to saline-treated animals. PD149163 produced hypothermia as
      expected but this effect did show tolerance over the course of the study, unlike
      feeding. The results suggest that NT1 receptor agonists are candidates for
      treatment of obesity and that somewhat different mechanisms are involved in NT1
      induced feeding regulation and temperature regulation.

PMID- 19596359
TI  - Sensorimotor gating in neurotensin-1 receptor null mice.
AB  - BACKGROUND: Converging evidence has implicated endogenous neurotensin (NT) in the
      pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition
      of the startle reflex (PPI) is a measure of sensorimotor gating and considered to
      be of strong relevance to neuropsychiatric disorders associated with psychosis
      and cognitive dysfunction. Mice genetically engineered to not express NT display
      deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1
      receptors have been most strongly implicated in mediating the psychosis relevant
      effects of NT such as attenuating PPI deficits. To investigate the role of NT1
      receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and
      NT1 knockout (KO) mice. We also tested the effects of amphetamine and
      dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce
      PPI as well as the NT1 selective receptor agonist PD149163, known to increase PPI
      in rats. METHODS: Baseline PPI and acoustic startle response were measured in WT
      and NT1 KO mice. After baseline testing, mice were tested again after receiving
      intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and
      10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0
      mg/kg) on separate test days. RESULTS: Baseline PPI and acoustic startle response
      in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice
      exhibited similar responses to the PPI-disrupting effects of dizocilpine and
      amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the
      acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS: The
      data does not support the regulation of baseline PPI or the PPI disruptive
      effects of amphetamine or dizocilpine by endogenous NT acting at the NT1
      receptor, although they support the antipsychotic potential of pharmacological
      activation of NT1 receptors by NT1 agonists.

PMID- 19596360
TI  - Arginine vasopressin gene expression changes within the nucleus accumbens during
      environment elicited cocaine-conditioned response in rats.
AB  - It is known that changes in gene expression within the nucleus accumbens (NAc)
      occur during cocaine dependence development. However, identification of specific
      genes involved in cocaine conditioning awaits further investigation. We conducted
      a high throughput gene expression profile analysis of the NAc, during different
      stages of the environment-elicited cocaine conditioning. Rats were assigned to
      two different environmental conditions. Cocaine conditioned group received a
      cocaine injection (10mg/kg, i.p.) prior to being placed in the activity chambers.
      Control rats received saline injections before being exposed to their
      environment. Both groups received a saline injection in their home cage.
      Conditioning training lasted for 10 days. Animals were then re-exposed to their
      previously paired environments only on day 12 (test session). We found that the
      gene for arginine vasopressin (AVP) was differentially expressed on experimental
      subjects during all stages of environment-elicited cocaine conditioning. To
      further validate our molecular results, biochemical and immunolocalization
      experiments were conducted. We found the presence of AVP within accumbal fibers
      and changes in AVP protein levels following cocaine conditioning. Moreover, we
      tested the effects of accumbal microinfusions of either AVP receptor V(1A)
      agonist [pGlu(4), Cyt6, Arg(8)] AVP 4-9 1.0 ng/0.5 microl, or V(1A) antagonist
      (CH2) 5[Tyr (Me) 2] AVP, 1.0 ng/0.5 microl or vehicle solution (0.9% saline
      solution) during different stages of the cocaine conditioning. Blockade of V(1A)
      receptors within the NAc during acquisition interrupted the expression of the
      conditioned response, while activation leads to an increase in this response. Our
      findings propose a new role for AVP in cocaine addiction.

PMID- 19596361
TI  - GABAergic amacrine cells and visual function are reduced in PAC1 transgenic mice.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) and its high affinity
      receptor PAC1 are expressed in mammalian retina and involved in processing light
      information. However, their roles during retinogenesis remain largely elusive.
      Previously, we have generated transgenic mice overexpressing the human PAC1
      receptor, and shown that PACAP signaling is essential for normal development of
      the central nervous system. In this study, we show for the first time that PACAP
      signaling plays an important role in the development of retina, particularly in
      the genesis of GABAergic amacrine cells. Overexpression of the PAC1 receptor
      leads to an early exit from retinal proliferation, reduced production of
      GABAergic neurons, and a marked decline in visual function. These data
      demonstrate that an appropriate level of PACAP signaling is required for normal
      retinogenesis and visual function. This finding may have implications in
      GABAergic neuron-related neurological conditions.

PMID- 19596362
TI  - Down-regulation of GluK2 kainate receptor expression by chronic treatment with
      mood-stabilizing anti-convulsants or lithium in cultured astrocytes and brain,
      but not in neurons.
AB  - Recent studies have indicated that glutamatergic transmission may be altered in
      bipolar disorder and affected by chronic treatment with mood-stabilizing drugs.
      Kainate receptors may be of special interest because i) they have a modulatory
      role in synaptic transmission, long-term potentiation (LTP) and long-term
      depression (LDP); and ii) involvement of the kainate receptor subunit GluK2
      (GluR6) in behavioral symptoms thought characteristic of mania has been
      demonstrated in knock-out mice. Glutamate receptors are expressed not only on
      neurons, but also on astrocytes, where they contribute to regulation of synaptic
      activity. We have previously shown that primary cultures of mouse astrocytes
      respond to chronic but not acute treatment with therapeutic relevant
      concentrations of any of the 'classical' mood-stabilizing drugs, lithium ion
      (Li(+)), carbamazepine or valproate, with changes in uptake of myo-inositol,
      cPLA(2) expression and intracellular pH. In the present work, we found i) similar
      gene expression of the GluK2 subunit of the kainate receptor family in primary
      cultures of mouse astrocytes and in brain in vivo; ii) a reduction of mRNA and
      protein expression of GluK2 in astrocytes and in brain after chronic treatment
      with carbamazepine but no effect in neurons; iii) similar down-regulation in
      astrocytes by oxcarbamazepine, valproic acid or Li(+), which all have mood
      stabilizing effect, but not by the anti-convulsant topiramate, which has no such
      activity; and iv) abrogation of a normally occurring glutamate-induced ERK
      phosphorylation in the cultured astrocytes after chronic treatment with any of
      the mood-stabilizing drugs mentioned above. Possible relationships between these
      and previously demonstrated effects are discussed.

PMID- 19596363
TI  - Angiotensin-converting enzyme insertion/deletion polymorphism has no effect on
      the risk of atherosclerotic stroke or hypertension.
AB  - BACKGROUND AND PURPOSE: Stroke is a heterogeneous multifactorial disease. Hence,
      a large number of candidate genes are involved in stroke pathophysiology, such as
      blood pressure regulation and atherosclerosis. Although angiotensin-converting
      enzyme insertion/deletion (ACE I/D) polymorphism is considered to have a role in
      hypertension, coronary artery disease, and myocardial infarction, its
      relationship with cerebrovascular disease and hypertension in stroke in different
      ethnic populations is still inconsistent. METHODS: ACE I/D polymorphism, detected
      by polymerase chain reaction (PCR), was studied in 97 patients with large-vessel
      and 60 patients with small-vessel atherosclerotic stroke (44 asymptomatic, 16
      symptomatic lacunes) and 85 healthy subjects with normal brain imaging. The
      demographic data, lipid profile and risk factors of patients and controls were
      obtained retrospectively. RESULTS: ACE genotypes were in Hardy-Weinberg
      equilibrium in both patients and controls. Prevalences of DD, ID and II genotype
      were 41%, 40%, and 19%, respectively, in the stroke group. Differences in ACE I/D
      polymorphism distribution were statistically insignificant between the groups.
      This lack of association between stroke and ACE I/D polymorphism did not change
      in the presence of traditional risk factors (hypertension, diabetes mellitus,
      smoking, and dyslipidemia). Although hypertension was significantly more common
      in the patient groups, ACE I/D polymorphism showed no effect on hypertension
      risk. This lack of association also did not change according to groups or in the
      presence of diabetes mellitus, male gender or smoking. CONCLUSION: ACE I/D
      polymorphism did not predict the risk of stroke or hypertension in our population
      living in the western Black Sea region of Turkey.

PMID- 19596364
TI  - Gestational diabetes mellitus: all Asians are not alike.
AB  - OBJECTIVE: To estimate the prevalence of gestational diabetes mellitus (GDM)
      prevalence estimates for subgroups of US Asian and Pacific Islander (API) women
      by using data from 2005 and 2006 birth certificates. METHODS: Using 2005-2006
      natality files from states that implemented the revised 2003 US birth
      certificate, which differentiates between GDM and preexisting diabetes (2005: 12
      states; 2006: 19 states), we calculated age-adjusted GDM prevalence estimates for
      API mothers who delivered singleton infants. RESULTS: Among 3,108,877 births, US
      APIs had a substantially higher age-adjusted prevalence of GDM (6.3%) than whites
      (3.8%), blacks (3.5%), or Hispanics (3.6%). Among API subgroups, age-adjusted GDM
      prevalence varied significantly, from 3.7% among women of Japanese descent to
      8.6% among women of Asian Indian descent. Foreign-born APIs had significantly
      higher GDM rates than US-born APIs except among women of Japanese and Korean
      ancestry. CONCLUSION: Overall, US API women have the highest risk for GDM among
      all US racial/ethnic groups. However, APIs are a heterogeneous group by genetic
      background, culture, and diet and other lifestyle behaviors. Our findings imply
      that, whenever possible, API subgroups should be evaluated separately in health
      research.

PMID- 19596365
TI  - Using tolerance intervals to assess recovery of mussel beds impacted by the Exxon
      Valdez oil spill.
AB  - Polycyclic aromatic hydrocarbons (PAH) have been measured in mussel tissues in
      early spring and summer since 1993 throughout Prince William Sound (PWS) and the
      Gulf of Alaska (GOA). Season-specific thresholds were established at reference
      sites to identify 'above background' total PAH levels. Thresholds were estimated
      using one-sided 99% tolerance limits. Thresholds were similar across reference
      sites but differed by an order of magnitude across seasons. Trends in total PAH
      since 1998 were assessed for sites impacted by the 1989 Exxon Valdez oil spill or
      the Alyeska Marine Terminal. Summer samples exhibited no trends; early spring
      samples declined. In early spring, all sites were judged 'recovered' by 2004; in
      summer, one site in western Prince William Sound and two in the western GOA
      exceeded thresholds by 11ng/g dry weight or less. Robust estimation methods
      prevented bias from observations affected by unknown releases or laboratory
      errors.

PMID- 19596366
TI  - [Cost of arterial hypertension according to levels of morbidity in primary care
      setting].
AB  - BACKGROUND AND OBJECTIVE: To determine the health care cost and the labour
      incapacity of hypertension (AHT) according to different levels of morbidity in
      primary care setting (PC). PATIENTS AND METHODS: Retrospective-multicentric
      design. Patients' >/=40 year from seven teams of PC (year 2007) were included.
      MAIN MEASURES: age, sex, cardiovascular co-morbidity, Charlson index and general
      morbidity levels (Adjusted Clinical Groups; low, moderate and high). It was
      established a model of direct costs (differentiating: fixed and variable [drugs,
      tests and referrals]) and indirect. Logistic regression analysis and ANCOVA was
      used for the model correction. Statistical significance: P<0.05. RESULTS: The
      prevalence of hypertension was 28.4% (95% confidence interval [CI]: 27.4-29.4%),
      mean age 67.5 (11.7) years and 56.7% of female. 73.2% of patients had moderate co
      morbidity (95% CI: 71.3-75.1%). The average/unit of the total cost was 1312
      euro.1 (range, low co-morbidity: 633.1 euro, moderately: 1297.2 euro and high:
      2307.8 euro, P<0.001). Healthcare cost represented 98.2% of the whole and
      medication 69.4%. Morbidity with high cardiovascular event (OR=3.5), smoking
      (OR=1.4) and obesity (OR=1.3), P=0.02 was associated. The correlation of the
      health cost and total cost with the episodes number was 51.4% and 50.6%
      respectively, P<0.001. CONCLUSIONS: Patients with AHT have a high health care
      cost, mainly in pharmacy. The total costs increase with age and level of general
      morbidity. The AHT should be considered in conjunction with other cardiovascular
      risk factors. The cost in work labour incapacity is low.

PMID- 19596367
TI  - [Analysis of knowledge of international criteria for authorship by the Spanish
      researchers].

PMID- 19596368
TI  - [Fixed drug eruption].

PMID- 19596369
TI  - [Relationship between chronic fatigue syndrome and type A behaviour].
AB  - BACKGROUND AND OBJECTIVE: To quantify the relationship between Chronic Fatigue
      Syndrome (CFS) and Type A Behaviour Pattern (TABP) PATIENTS AND METHOD: The
      Jenkins Activity Survey (JAS) was administered to 82 patients diagnosed with CFS
      to determine the prevalence of TABP. Subjects' mean z scores on the JAS were
      compared with those from the general population (healthy controls) and from
      patients with ischemic cardiopathy (pathologic controls). RESULTS: CFS patients'
      mean score on the JAS was 5 points higher than that of the general population
      (healthy controls) and 2 points higher than that of patients with ischemic
      cardiopathy. CONCLUSIONS: TABP appears to be related with CFS and should be taken
      into account in the treatment of these patients.

PMID- 19596371
TI  - Neuroprotection from diazinon-induced toxicity in differentiating murine N2a
      neuroblastoma cells.
AB  - In previous work, the outgrowth of axon-like processes by differentiating mouse
      N2a neuroblastoma cells was shown to be inhibited by exposure to 10 microM
      diazinon. In the present work, N2a cells were induced to differentiate for 24 h
      in the presence and absence of 10 microM diazinon and 20% (v/v) conditioned
      medium derived from differentiating rat C6 glioma cells. Cells were then stained
      or lysed for morphological and biochemical analyses, respectively. The data
      showed that co-treatment with conditioned medium prevented the neurite inhibitory
      effect of diazinon. Furthermore, a significant recovery was also observed in the
      reduced levels of neurofilament heavy chain (NFH), heat shock protein-70 (HSP-70)
      and growth-associated protein-43 (GAP-43) observed as a result of diazinon
      treatment in the absence of conditioned medium, as seen by densitometric analysis
      of Western blots of cell lysates probed with monoclonal antibodies N52, BRM-22
      and GAP-7B10. By contrast, no significant change was noted in the reactivity of
      cell lysates with antibodies against alpha- and beta-tubulin under any condition
      tested. After pre-incubation with a polyclonal anti-glial cell line-derived
      neurotrophic factor (GDNF) antibody, conditioned medium derived from rat C6
      glioma cells lost its ability to protect N2a cells against the neurite inhibitory
      effects of diazinon. In conclusion, these data demonstrate that C6 conditioned
      medium protects N2a cells from the neurite inhibitory effects of diazinon by
      blocking molecular events leading to axon damage and that GDNF is implicated in
      these effects.

PMID- 19596370
TI  - Animal models of autism spectrum disorders: information for neurotoxicologists.
AB  - Recent findings derived from large-scale datasets and biobanks link multiple
      genes to autism spectrum disorders. Consequently, novel rodent mutants with
      deletions, truncations and in some cases, overexpression of these candidate genes
      have been developed and studied both behaviorally and biologically. At the Annual
      Neurotoxicology Meeting in Rochester, NY in October of 2008, a symposium of
      clinicians and basic scientists gathered to present the behavioral features of
      autism, as well as strategies to model those behavioral features in mice and
      primates. The aim of the symposium was to provide researchers with up-to-date
      information on both the genetics of autism and how they are used in differing in
      vivo and in vitro animal models as well as to provide a background on the
      environmental exposures being tested on several animal models. In addition,
      researchers utilizing complementary approaches, presented on cell culture, in
      vitro or more basic models, which target neurobiological mechanisms, including
      Drosophila. Following the presentation, a panel convened to explore the
      opportunities and challenges of using model systems to investigate genetic and
      environment interactions in autism spectrum disorders. The following paper
      represents a summary of each presentation, as well as the discussion that
      followed at the end of the symposium.

PMID- 19596373
TI  - Total antioxidant status before and after bariatric surgery for type 2 diabetes
      mellitus.

PMID- 19596372
TI  - Heterogeneity of microglia and TNF signaling as determinants for neuronal death
      or survival.
AB  - Microglia do not constitute a single, uniform cell population, but rather
      comprise cells with varied phenotypes, some which are beneficial and others that
      may require active regulatory control. Thus, gaining a better understanding of
      the heterogeneity of resident microglia responses will contribute to any
      interpretation regarding the impact of any such response in the brain. Microglia
      are the primary source of the pro-inflammatory cytokine, tumor necrosis factor
      (TNF) that can initiate various effects through the activation of membrane
      receptors. The TNF p55 receptor contains a death domain and activation normally
      leads to cellular apoptosis; however, under specific conditions, receptor
      activation can also lead to the activation of NF-kappaB and contribute to cell
      survival. These divergent outcomes have been linked to receptor localization with
      receptor internalization leading to cell death and membrane localization
      supporting cell survival. A second TNF receptor, TNF p75 receptor, is normally
      linked to cell growth and survival, however, it can cooperate with the p55
      receptor and contribute to cell death. Thus, while an elevation in TNFalpha in
      the brain is often considered an indicator of microglia activation and
      neuroinflammation, a number of factors come into play to determine the final
      outcome. Data are reviewed demonstrating that heterogeneity in morphological
      response of microglia and the expression of TNFalpha and TNF receptors are
      critical in identifying and characterizing neurotoxic events as they relate to
      neuroinflammation, neuronal damage and in stimulating neuroprotection.

PMID- 19596377
TI  - A high performance liquid chromatography method with electrochemical detection of
      gamma-aminobutyric acid, glutamate and glutamine in rat brain homogenates.
AB  - Determination of gamma-aminobutyric acid (GABA), glutamate (Glu) and glutamine
      (Gln) in animal models has been important to understand the normal function and
      clinical aspects of some neurological diseases. Quantification of these amino
      acid transmitters has conventionally been performed by using a high performance
      liquid chromatography (HPLC) system. This paper describes an improved HPLC method
      with electrochemical detection for glutamate, glutamine and GABA determination in
      brain homogenates. The protocol is based on a precolumn derivatization of amino
      acids with o-phthalaldehyde and sodium sulfite, a separation through a C18, 5
      microm particle size column and an isocratic elution. Several modifications of
      previous works on methanol percentage, pH, temperature, flow rate and
      derivatization solution concentration were done to obtain a suitable protocol for
      amino acid quantification in brain homogenate samples. Total elution time is 35
      min approximately. Technical requirements and laboratory expenses of this new
      protocol are minimal. This technique showed high linearity, repeatability and
      accuracy.

PMID- 19596376
TI  - Chronic neuromuscular electrical stimulation of paralyzed hindlimbs in a rodent
      model.
AB  - Neuromuscular electrical stimulation (NMES) can be used to activate paralyzed or
      paretic muscles to generate functional or therapeutic movements. The goal of this
      research was to develop a rodent model of NMES-assisted movement therapy after
      spinal cord injury (SCI) that will enable investigation of mechanisms of NMES
      induced plasticity, from the molecular to systems level. Development of the model
      requires accurate mapping of electrode and muscle stimulation sites, the
      capability to selectively activate muscles to produce graded contractions of
      sufficient strength, stable anchoring of the implanted electrode within the
      muscles and stable performance with functional reliability over several weeks of
      the therapy window. Custom designed electrodes were implanted chronically in
      hindlimb muscles of spinal cord transected rats. Mechanical and electrical
      stability of electrodes and the ability to achieve appropriate muscle recruitment
      and joint angle excursion were assessed by characterizing the strength duration
      curves, isometric torque recruitment curves and kinematics of joint angle
      excursion over 6-8 weeks post implantation. Results indicate that the custom
      designed electrodes and implantation techniques provided sufficient anchoring and
      produced stable and reliable recruitment of muscles both in the absence of daily
      NMES (for 8 weeks) as well as with daily NMES that is initiated 3 weeks post
      implantation (for 6 weeks). The completed work establishes a rodent model that
      can be used to investigate mechanisms of neuroplasticity that underlie NMES-based
      movement therapy after spinal cord injury and to optimize the timing of its
      delivery.

PMID- 19596375
TI  - Rapid isolation and culture of primary microglia from adult mouse spinal cord.
AB  - Microglia are important in homeostasis and widely considered to have roles in the
      pathogenesis of conditions such as neuropathic pain and multiple sclerosis. The
      need to study microglia from the adult spinal cord is essential to further
      understand the role of these cells in disease pathology. Primary microglia are
      often prepared from brain tissues obtained from embryonic or perinatal age
      rodents and the process can take over a week to complete. The protocol in this
      study provides rapid isolation of microglia from adult spinal cord, allowing
      immediate availability for experimentation of both ex vivo and in vitro within a
      few hours. A purity of 99% with little or no neuronal or astrocytic contamination
      can be achieved. Between 70% and 85% of these adult microglia were in a
      relatively non-activated state. Functionally, these microglia respond to
      lipopolysaccharide incubation with increases in both phospho-p38 MAPK and OX42
      immunostaining, as well as release of ATP, as compared to un-stimulated
      microglia. This technique provides a protocol to achieve rapid and efficient
      extraction of high purity, quiescent and functionally active microglia from adult
      mouse spinal cord, allowing greater study of adult spinal microglia in
      physiological and pathophysiological states.

PMID- 19596378
TI  - Magnetic insertion system for flexible electrode implantation.
AB  - Chronic recording electrodes are a vital tool for brain research and neural
      prostheses. Despite decades of advances in recording technology, probe structures
      and implantation methods have changed little over time. Then as now, compressive
      insertion methods require probes to be constructed from hard, stiff materials,
      such as silicon, and contain a large diameter shank to penetrate the brain,
      particularly for deeper structures. The chronic presence of these probes results
      in an electrically isolating glial scar, degrading signal quality over time. This
      work demonstrates a new magnetic tension-based insertion mechanism that allows
      for the use of soft, flexible, and thinner probe materials, overcoming the
      materials limitations of modern electrodes. Probes are constructed from a sharp
      magnetic tip attached to a flexible tether. A pulsed magnetic field is generated
      in a coil surrounding a glass pipette containing the electrode. The applied field
      pulls the electrode tip forward, accelerating the probe into the neural tissue
      with a penetration depth that is calibrated against the charge voltage.
      Mathematical modeling and agar gel insertion testing demonstrate that the
      electrode can be implanted to a predictable depth given system specific
      parameters. Trial rodent implantations resulted in discernible single-unit
      activity on one of the probes. The current prototype demonstrates the feasibility
      of a tension based, magnetically driven implantation system and opens the door to
      a wide variety of new minimally invasive probe materials and configurations.

PMID- 19596379
TI  - A single tube, quantitative real-time RT-PCR assay that detects four potato
      viruses simultaneously.
AB  - A high throughput, real-time multiplex, single tube RT-PCR assay was developed
      for simultaneous detection of Potato leafroll virus (PLRV), Potato virus X (PVX)
      and Potato virus S (PVS) in potato leaves and tubers, and Tomato spotted wilt
      virus (TSWV) in potato tubers and tomato leaves. The test uses four different
      fluorescently labelled TaqMan probes. Limits of detection sensitivity were
      established using a range of virus transcript copy numbers (8 x 10(1) to 8 x
      10(9) copies of PVX and PVS, 1 x 10(2) to 1 x 10(10) copies of PLRV and 1 x 10(3)
      to 1 x 10(10) copies of TSWV). For each individual assay, the inter-assay
      reproducibility was high, with a coefficient of variation of the combined assays
      of <2%. Total RNA was extracted rapidly and efficiently from bulked samples
      equivalent to 300 dormant tubers to detect single infections of PLRV, PVX, PVS
      and TSWV simultaneously in a single assay. The multiplexed assay was validated in
      blind studies with leaves and tubers. This high-throughput test is accurate and
      sensitive, and provides seed potato industries with a cost-effective diagnostic
      tool to detect viruses reliably in bulked samples of dormant potato tubers.

PMID- 19596380
TI  - [Black bone disease of the skull and facial bones].
AB  - INTRODUCTION: We report the case of a patient with a craniofacial black bone
      disease. This was discovered accidentally during a coronal approach. CASE REPORT:
      A 38-year-old patient was referred to our unit for facial palsy having appeared
      10 years before. Rehabilitation of the facial palsy was performed with a
      lengthening temporal myoplasty and lengthening of the upper eyelid elevator. An
      unusual black color of the skull was observed at incision of the coronal
      approach. Subperiostal dissection of skull and malars confirmed the presence of a
      black bone disease. A postoperative history revealed minocycline intake (200mg
      per day) during 3 years. DISCUSSION: This craniofacial black bone disease was
      caused by minocycline intake. The originality of this case is to see directly the
      entire craniofacial skeleton black. This abnormal pigmentation may affect various
      organs or tissues. Bone pigmentation is irreversible unlike that of the mouth
      mucosa or of the skin. This abnormal pigmentation is usually discovered
      accidentally.

PMID- 19596382
TI  - [Immunomodulatory treatments for multiple sclerosis: lessons from direct
      comparative studies].
AB  - INTRODUCTION: Several first-line immunomodulatory treatments are available to
      physicians for treating patients with relapsing-remitting multiple sclerosis,
      namely three interferon-beta preparations and glatiramer acetate. In order to
      enlighten their choice of treatment, physicians need data from good quality
      comparative clinical trials. METHODS: This review outlines and compares the
      findings of the various randomized clinical trials that have assessed the
      efficacy and safety of immunomodulatory treatments for multiple sclerosis. Six
      such studies have been reported to date, a Danish study (interferon-beta 1a sc
      versus interferon-beta 1b sc), the EVIDENCE study (interferon-beta 1a sc versus
      interferon-beta 1a im), the INCOMIN study (interferon-beta 1b sc versus
      interferon-beta 1a im), the BECOME and BEYOND studies (interferon-beta 1b sc
      versus glatiramer acetate) and the REGARD study (interferon-beta 1a sc versus
      glatiramer acetate). RESULTS: These studies have demonstrated somewhat superior
      efficacy for interferon-beta preparations administered subcutaneously several
      times a week compared to preparations administered intramuscularly once a week.
      In contrast, no difference in efficacy has been demonstrated between the two
      subcutaneously administered interferon-beta preparations, or between either of
      these preparations and glatiramer acetate. Differences in the safety profile of
      the four immunomodulatory treatments were observed, in particular a more
      favorable skin tolerance with intramuscularly administered interferon-beta and a
      better systemic adverse event profile for glatiramer acetate. CONCLUSIONS: These
      various randomized comparative trials have provided objective criteria that can
      be used by physicians for choosing between immunomodulatory treatments.

PMID- 19596384
TI  - Early-night serial awakenings as a new paradigm for studies on NREM dreaming.
AB  - A new experimental paradigm called "Early-Night Serial Awakenings" (ENSA) was
      explored to find out its strengths and weaknesses for psychophysiological studies
      of NREM sleep dreaming. Five participants spent 20 experimental nights in the
      sleep laboratory, and were serially awakened with approximately 24-minute
      intervals during Stages 2 and 3 of NREM sleep. As a total, 164 awakenings were
      conducted during the sessions that lasted on average 193 min. Altogether, 30% of
      NREM sleep awakenings led to dream reports, 39% to reports of white dreaming, and
      31% to reports of dreamless sleep. Results also show that sleep EEG spectral
      power, dream recall frequency as well as dream complexity remained stable
      throughout the serial awakening sessions. We conclude that, as ENSA dreams
      appeared to be static and very limited in content, the paradigm we identified
      could be used in future studies to reveal the psychophysiological mechanisms of
      relatively simple forms of early-night NREM sleep dreaming.

PMID- 19596381
TI  - Functionalization of a nanopore: the nuclear pore complex paradigm.
AB  - Biological cells maintain a myriad of nanopores which, although relying on the
      same basic small-hole principle, serve a large variety of functions. Here we
      consider how the nuclear pore complex (NPC), a large nanopore mediating the
      traffic between genetic material and protein synthesizing apparatus, is
      functionalized to carry out a set of transport functions. A major parameter of
      NPC functionalization is a lining of it external and internal surfaces with so
      called phenylalanine glycine (FG) proteins. FG proteins integrate a multitude of
      transport factor binding sites into intrinsically disordered domains. This
      surprising finding has given rise to a number of transport models assigning
      direct gating functions to FG proteins. However, recent data suggest that the
      properties of FG proteins cannot be properly assessed by considering only the
      purified, transport-factor-stripped NPC. At physiological conditions transport
      factors may shape FG proteins in a way allotting an essential role to surface
      diffusion, reconciling tight binding with efficient transport. Thus, NPC studies
      are revealing both general traits and novel aspects of nanopore
      functionalization. In addition, they inspire artificial molecule sorters for
      proteomic and pharmaceutical applications.

PMID- 19596386
TI  - Functional role of Alix in HIV-1 replication.
AB  - Retroviral Gag proteins encode small peptide motifs known as late domains that
      promote the release of virions from infected cells by interacting directly with
      host cell factors. Three types of retroviral late domains, with core sequences
      P(T/S)AP, YPX(n)L, and PPPY, have been identified. HIV-1 encodes a primary
      P(T/S)AP-type late domain and an apparently secondary late domain sequence of the
      YPX(n)L type. The P(T/S)AP and YPX(n)L motifs interact with the endosomal sorting
      factors Tsg101 and Alix, respectively. Although biochemical and structural
      studies support a direct binding between HIV-1 p6 and Alix, the physiological
      role of Alix in HIV-1 biology remains undefined. To elucidate the function of the
      p6-Alix interaction in HIV-1 replication, we introduced a series of mutations in
      the p6 Alix binding site and evaluated the effects on virus particle production
      and virus replication in a range of cell types, including physiologically
      relevant primary T cells and macrophages. We also examined the effects of the
      Alix binding site mutations on virion morphogenesis and single-cycle virus
      infectivity. We determined that the p6-Alix interaction plays an important role
      in HIV-1 replication and observed a particularly severe impact of Alix binding
      site mutations when they were combined with mutational inactivation of the Tsg101
      binding site.

PMID- 19596388
TI  - Auditory brain response modified by temporal deviation of language rhythm: an
      auditory event-related potential study.
AB  - The effects of the temporal disruption of language rhythm in Japanese on auditory
      evoked potentials were investigated in normal subjects. Auditory event-related
      evoked potentials (AERP) were recorded following syllables using a natural and
      deviated language rhythm by inserting various (0-400 ms) silent intervals between
      syllables. The language speed was changed to assess the effect of a deviant
      rhythm relative to the language speed on AERP in another experiment. The
      prolonging of intervals did not affect the N100-P150 components until the
      inserted interval became 400 ms, while the negative component (early negativity,
      EN), peaking at 250-300 ms, was enhanced when the interval was 100 ms or more.
      The N100-P150 components following deviated language rhythms did not change
      during the fast speed but did in the standard and slow speed. We considered that
      the N100-P150 components were changed by the mixed effects of adaptation and
      prediction related to the reading speed, and that EN was evoked by deviated
      language rhythm in a different way from that caused N100-P150 changes, possibly
      via mismatch detection process between deviant rhythm and intrinsic rehearsed
      rhythm.

PMID- 19596385
TI  - Modified vaccinia virus Ankara can activate NF-kappaB transcription factors
      through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway
      during the early phase of virus replication.
AB  - Modified vaccinia virus Ankara (MVA), which is a promising replication-defective
      vaccine vector, is unusual among the orthopoxviruses in activating NF-kappaB
      transcription factors in cells of several types. In human embryonic kidney (HEK
      293T) cells, the MVA-induced depletion of IkappaBalpha required to activate NF
      kappaB is inhibited by UV-inactivation of the virus, and begins before viral DNA
      replication. In HEK 293T, CHO, or RK13 cells, expression of the cowpox virus CP77
      early gene, or the vaccinia virus K1L early gene suppresses MVA-induced
      IkappaBalpha depletion. In mouse embryonic fibroblasts (MEFs), MVA induction of
      IkappaBalpha depletion is dependent on the expression of mouse or human double
      stranded RNA-activated protein kinase (PKR). These results demonstrate that
      events during the early phase of MVA replication can induce PKR-mediated
      processes contributing both to the activation of NF-kappaB signaling, and to
      processes that may restrict viral replication. This property may contribute to
      the efficacy of this vaccine virus.

PMID- 19596389
TI  - Degradation of Acid Orange 7 using magnetic AgBr under visible light: the roles
      of oxidizing species.
AB  - AgBr was creatively immobilized on a magnetic substrate (SiO(2)-coated Fe(3)O(4)
      nanoparticle, SFN) to achieve magnetic separation after visible light-driven
      photocatalytic oxidation (PCO). The resulted Ag/AgBr/SFN was characterized by
      TEM, vibrating sample magnetometer and other techniques. It is found that the
      average diameter of the Ag/AgBr/SFN particle is less than 20 nm. The typical
      superparamagnetic behavior of Ag/AgBr/SFN implies that the catalyst can be
      magnetically separated. The physicochemical features of the used Ag/AgBr/SFN
      after visible light irradiation were not dramatically changed by X-ray
      diffraction, UV-Vis diffuse reflectance spectra and Fourier transform-infrared
      analysis. SiO(2) interlayer was proven to slightly increase the degradation
      efficiency for an azo dye Acid Orange 7. UV-Vis spectra and HPLC analysis
      indicated that the dye was oxidized and decomposed. The photoactivity of
      Ag/AgBr/SFN was partly maintained after successive PCO under visible light. In
      order to evaluate the roles of e(-)-h(+) pairs and reactive oxygen species, the
      quenching effect was examined by employing Ag/AgBr/SFN and commercial TiO(2) (P
      25) under visible light (lambda>400 nm) and UV-A irradiation, respectively.
      Active h(+) and the resulting (*)OH played the major roles for degradation. The
      effect of active h(+) and (*)OH were proven to be highly dependent on the
      concentration of photocatalysts. The effect of (*)OH was more obvious for P-25,
      while that of active h(+) was more predominant for Ag/AgBr/SFN.

PMID- 19596387
TI  - Immunohistochemical evaluation of the protein expression of nerve growth factor
      and its TrkA receptor in rat limbic regions following electroshock seizures.
AB  - Repeated (but not acute) exposure to brief, non-injurious seizures evoked by
      minimal electroconvulsive shock (ECS) decreases neuronal death in limbic system
      and increases mRNA levels for nerve growth factor (NGF). Thus, the induction of
      NGF is a potential mechanism for the neuroprotection evoked by repeated ECS. The
      neuroprotective action of NGF is mediated by the TrkA receptor. This study
      determined whether repeated ECS exposure increased TrkA and NGF protein levels.
      To determine the functional significance of changes in these proteins, we
      compared the effects of ECS given daily either for 7 days (chronic ECS) or for 1
      day (acute ECS). After chronic ECS, upregulation of both NGF and TrkA was found
      in perirhinal cortex, thalamus, and amygdala. In hippocampus, TrkA was
      upregulated in CA2, CA3 and CA4. NGF increase in hippocampus was found in CA1 and
      dentate gyrus. In frontal cortex and substantia innominata, an increase in NGF
      (but not in TrkA) was found. In most brain regions, TrkA and NGF remained
      unchanged after acute ECS. Our results demonstrate that repeated exposure to ECS
      causes an upregulation of TrkA and NGF proteins in several limbic areas in which
      neuroprotective effects are observed suggesting that NGF contributes to ECS
      evoked neuroprotection.

PMID- 19596390
TI  - Inhibition of white spot syndrome virus replication in Penaeus monodon by
      combined silencing of viral rr2 and shrimp PmRab7.
AB  - Although a significant progress has been achieved on dsRNA mediated anti-virus
      strategy development, there is still no effective means to control the virulent
      white spot syndrome virus (WSSV). Six double-stranded RNAs specific to different
      essential genes of WSSV (ie1, ie3, pol (DNA polymerase), rr2 (ribonucleotide
      reductase small subunit), vp26, and vp28) were employed to suppress viral
      replication in shrimp. At the condition that non-specific inhibitory effect was
      overwhelmed, the relative protective degree of these dsRNAs against WSSV
      infection (rr2>ie3>vp26, vp28>ie1>pol) was observed by semi-quantitative PCR.
      Besides, more than one injection of dsRNA was needed for an efficient viral
      inhibition. To improve viral protection in Penaeus monodon, synchronized blocking
      of viral cellular transport (by dsRNA-PmRab7) and viral essential gene synthesis
      (by dsRNA-rr2) was first performed in this study. The suppression effects of
      shrimp mortality by either combined dsRNAs of rr2 and PmRab7 or dsRNA-rr2 alone
      was monitored for 8 days after viral challenge. Approximately 95% of shrimp
      survivals were detected from both combined dsRNAs and dsRNA-rr2 alone whereas all
      shrimp without dsRNA were dead. It revealed that there was no additive inhibitory
      effect of the combined dsRNAs over dsRNA-rr2 alone.

PMID- 19596391
TI  - The nuclear localization signal of the NS1 protein is essential for Periplaneta
      fuliginosa densovirus infection.
AB  - The regulatory protein NS1 is a key molecule in life cycle of Periplaneta
      fuliginosa densovirus (PfDNV). When we ectopically expressed the PfDNV NS1
      protein in non-P. fuliginosa insect cells, the NS1 protein could not enter the
      nucleus and remained in the cytosol. However, the NS1 was localized to both the
      cytosol and nucleus of cockroach hemocyte cells. So we investigated the abilities
      of the potential nuclear localization signal (NLS) of P. fuliginosa Densovirus
      non-structural protein 1 (NS1) to translocate NS1 and a carrier protein to the
      nucleus following transfection into insect cells. Possible nuclear localization
      sequences were chosen from the NS1 on the basis of the presence of basic
      residues, which is a common theme in most of the previously identified targeting
      peptides. Nuclear localization activity was found within the residues 252-257
      (RRRRRR) of the NS1, while replacement of a single arginine in this region with
      glycine abolished it. The targeting activity was enhanced with the arginine
      residues added.

PMID- 19596392
TI  - Antifeedant activity and high mortality in the pea aphid Acyrthosiphon pisum
      (Hemiptera: Aphidae) induced by biostable insect kinin analogs.
AB  - The insect kinins are multifunctional neuropeptides found in a variety of
      arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera:
      Aphidae). A series of biostable insect kinin analogs based on the shared C
      terminal pentapeptide core region were fed in solutions of artificial diet to the
      pea aphid over a period of 3 days and evaluated for antifeedant and aphicidal
      activity. The analogs contained either alpha,alpha-disubstituted or beta-amino
      acids in key positions to enhance resistance to tissue-bound peptidases and
      retain activity in a number of insect kinin bioassays and/or on expressed
      receptors. Three of the biostable analogs demonstrated antifeedant activity, with
      a marked reduction in honeydew formation observed after 1 day, and very high
      mortality. In contrast, an unmodified, parent insect kinin and two other analogs
      containing some of the same structural components that promote biostability are
      inactive. The most active analog, double Aib analog K-Aib-1 ([Aib]FF[Aib]WGa),
      featured aphicidal activity calculated at an LC(50) of 0.063 nmol/microl (0.048
      microg/microl) and an LT(50) of 1.68 days, matching the potency of some
      commercially available aphicides. The mechanism of this activity has yet to be
      established. The aphicidal activity of the biostable insect kinin analogs may
      result from different potential mechanisms as disruption of digestive processes
      by interfering with gut motility patterns, digestive enzyme release, and/or with
      fluid cycling in the gut, and also nutrient transport across the gut itself; all
      processes shown to be regulated by the insect kinins in other insects. However
      the mechanism(s) is(are) not yet known. The active insect kinin analogs represent
      potential leads in the development of selective, environmentally friendly pest
      aphid control agents.

PMID- 19596393
TI  - Extensive bacterial diversity indicates the potential operation of a dynamic
      micro-ecology within domestic rainwater storage systems.
AB  - The concept that domestic rainwater storage tanks may host sustainable microbial
      ecosystems has not previously been addressed. The bacterial diversity, cultivated
      from more than 80 samples from 22 tanks at various locations across eastern
      Australia, is presented here as prima facie evidence for the potential operation
      of a functional micro-ecology within rainwater storage systems. Cultivated
      isolates were found to comprise members of four major bacterial divisions;
      Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes, including more than
      200 species from 80 different genera. The pattern of abundance distribution was
      typical of that observed in most natural communities, comprising a small number
      of abundant taxa and a multitude of rare taxa, while the specific composition
      resembled that previously described in a number of natural aquatic systems.
      Although Proteobacteria from alpha, beta and gamma sub-classes were dominant, a
      set of core taxa comprising representative genera from all four phyla could be
      identified. Coliform and other species specifically associated with faecal
      material comprised <15% of the species identified, and represented <1.5% of total
      average abundance. The composition of the cultivated populations and scope of
      diversity present, suggested that rainwater tanks may support functional
      ecosystems comprising complex communities of environmental bacteria, which may
      have beneficial implications for the quality of harvested rainwater.

PMID- 19596394
TI  - Aerodynamic effects of trees on pollutant concentration in street canyons.
AB  - This paper deals with aerodynamic effects of avenue-like tree planting on flow
      and traffic-originated pollutant dispersion in urban street canyons by means of
      wind tunnel experiments and numerical simulations. Several parameters affecting
      pedestrian level concentration are investigated, namely plant morphology,
      positioning and arrangement. We extend our previous work in this novel aspect of
      research to new configurations which comprise tree planting of different crown
      porosity and stand density, planted in two rows within a canyon of street width
      to building height ratio W/H=2 with perpendicular approaching wind. Sulfur
      hexafluoride was used as tracer gas to model the traffic emissions. Complementary
      to wind tunnel experiments, 3D numerical simulations were performed with the
      Computational Fluid Dynamics (CFD) code FLUENT using a Reynolds Stress turbulence
      closure for flow and the advection-diffusion method for concentration
      calculations. In the presence of trees, both measurements and simulations showed
      considerable larger pollutant concentrations near the leeward wall and slightly
      lower concentrations near the windward wall in comparison with the tree-less
      case. Tree stand density and crown porosity were found to be of minor importance
      in affecting pollutant concentration. On the other hand, the analysis indicated
      that W/H is a more crucial parameter. The larger the value of W/H the smaller is
      the effect of trees on pedestrian level concentration regardless of tree
      morphology and arrangement. A preliminary analysis of approaching flow velocities
      showed that at low wind speed the effect of trees on concentrations is worst than
      at higher speed. The investigations carried out in this work allowed us to set up
      an appropriate CFD modelling methodology for the study of the aerodynamic effects
      of tree planting in street canyons. The results obtained can be used by city
      planners for the design of tree planting in the urban environment with regard to
      air quality issues.

PMID- 19596395
TI  - Incorporating pelvic/vaginal reconstruction into radical pelvic surgery.
AB  - OBJECTIVE: The objective of this review is to discuss the more common surgical
      scenarios that often require pelvic/vaginal reconstruction with an emphasis on
      incorporating reconstructive options into the pelvic exenteration. METHODS: A
      review of the literature regarding pelvic/vaginal reconstruction in patients
      undergoing radical pelvic surgery was performed and supplemented with the
      authors' own experience. RESULTS: Reconstructive surgical procedures are often
      necessary with outcome goals that include any combination of enhanced wound
      healing, decrease in acute and chronic morbidity, and restoration of anatomic
      form and function. Many reconstruction techniques are available including, but
      not limited to, skin grafting, simple tissue transposition flaps, fasciocutaneous
      flaps, and myocutaneous flaps. It is extremely important that the gynecologic
      oncologist be proficient with more than one of the reconstructive options
      available to address the various pelvic/vaginal defects one may encounter. There
      is a wide range in the complexity of surgical situations requiring
      reconstruction. The pelvic exenteration in the previously radiated patient offers
      the highest level of challenge in terms of pre-operative planning, intra
      operative decision-making and surgical skills. Vaginal reconstruction for sexual
      intercourse may be a priority for some patients, however pelvic/vaginal
      reconstruction plays a major role in facilitating wound healing, minimizing
      significant morbidity, and improving patient quality of life and functional
      outcomes. CONCLUSIONS: The gynecologic oncologist is best suited to orchestrate
      this multifaceted surgical process. It is extremely important that the
      gynecologic oncologist be well versed in the reconstructive options available in
      order that it is optimally planned and effected at the primary surgical
      procedure.

PMID- 19596396
TI  - Strategies to promote differentiation of newborn neurons into mature functional
      cells in Alzheimer brain.
AB  - Adult neurogenesis occurs in the subgranular zone (SGZ) and subventricular zone
      (SVZ). New SGZ neurons migrate into the granule cell layer of the dentate gyrus
      (DG). New SVZ neurons seem to enter the association neocortex and entorhinal
      cortex besides the olfactory bulb. Alzheimer disease (AD) is characterized by
      neuron loss in the hippocampus (DG and CA1 field), entorhinal cortex, and
      association neocortex, which underlies the learning and memory deficits. We
      hypothesized that, if the AD brain can support neurogenesis, strategies to
      stimulate the neurogenesis process could have therapeutic value in AD. We
      reviewed the literature on: (a) the functional significance of adult-born
      neurons; (b) the occurrence of endogenous neurogenesis in AD; and (c) strategies
      to stimulate the adult neurogenesis process. We found that: (a) new neurons in
      the adult DG contribute to memory function; (b) new neurons are generated in the
      SGZ and SVZ of AD brains, but they fail to differentiate into mature neurons in
      the target regions; and (c) numerous strategies (Lithium, Glatiramer Acetate,
      nerve growth factor, environmental enrichment) can enhance adult neurogenesis and
      promote maturation of newly generated neurons. Such strategies might help to
      compensate for the loss of neurons and improve the memory function in AD.

PMID- 19596397
TI  - Systematic evaluation of the antioxidant potential of different parts of
      Foeniculumvulgare Mill. from Portugal.
AB  - Fennel (Foeniculum vulgare Mill.) is a widespread perennial umbeliferous
      (Apiaceae) herb, traditionally used for medicinal purposes and human consumption.
      It is highly recommended for diabetes, bronchitis and chronic coughs, and for the
      treatment of kidney stones; some of those chronic diseases are related to the
      production of radical species involved in the oxidative stress. Therefore, the
      antioxidant potential of this herb might explain some of their empirical uses in
      folk medicine. This is the first time that a systematic study on different parts
      of fennel is performed, in order to understand differences in the antioxidant
      potential of shoots, leaves, steams, and inflorescences, particularly related to
      their composition in antioxidant compounds such as vitamins (ascorbic acid and
      tocopherols) and phenolics. The shoots seems to have the highest radical
      scavenging activity and lipid peroxidation inhibition capacity (EC(50) values<1.4
      mg/ml), which is in agreement with the highest content in phenolics (65.85+/-0.74
      mg/g) and ascorbic acid (570.89+/-0.01 microg/g) found in this part. The shoots
      also revealed high concentration of tocopherols (34.54+/-1.28 microg/g) and were
      the only part with flavonoids.

PMID- 19596399
TI  - Mathematical modeling in metal metabolism: overview and perspectives.
AB  - A review of mathematical modeling in metal metabolism is presented. Both
      endogenous and exogenous metals are considered. Four classes of methods are
      considered: Petri nets, multi-agent systems, determinist models based on
      differential equations and stochastic models. For each, a basic theoretical
      background is given, then examples of applications are given, detailed and
      commented. Advantages and disadvantages of each class of model are presented. A
      special attention is given to determinist differential equation models, since
      almost all models belong to this class.

PMID- 19596398
TI  - Effect of wastewater intake on antioxidant and marker enzymes of tissue damage in
      rat tissues: implications for the use of biochemical markers.
AB  - In the present study, alteration in antioxidant enzymes superoxide dismutase
      (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase
      (GST) and glutathione peroxidase (GPx) and marker enzymes of tissue damage
      alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase
      (ALP) with laboratory exposure to wastewaters from Aligarh (AWW) and Saharanpur
      (SWW) were investigated in rat liver and kidney. Levels of malondialdehyde (MDA),
      reduced glutathione (GSH) and hydrogen peroxide (H(2)O(2)) were also determined.
      A profound enhancement of 5 and 2.5-folds in MDA level was recorded in the liver
      and kidney respectively as a result of oral administration of SWW to the rats.
      Exposure to both AWW and SWW resulted in 3-4-fold increase in GR activity and 3
      fold increase in SOD and ALT activity in the hepatic tissue compared to control
      values. Ingestion of AWW and SWW resulted in 3.5-fold rise in renal AST levels
      whereas AWW caused 75% decline in GST activity in kidney of treated rats. Results
      indicate that wastewater (AWW/SWW) caused severe damage to renal and hepatic
      tissues and the effect seems in part to be mediated by suppression of antioxidant
      system with GR and SOD as potential candidates for hepatic toxicity biomarkers of
      wastewaters.

PMID- 19596400
TI  - Anaphylactic reaction to (mixed) fruit juice containing dragon fruit.

PMID- 19596401
TI  - DNA sequence analysis of the conserved region around the SOD1 gene locus in
      recessively inherited ALS.
AB  - Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases;
      12-23% are associated with mutations in the Cu/Zn superoxide dismutase gene
      (SOD1). All ALS-linked SOD1 mutations present with a dominant pattern of
      inheritance apart from the aspartate to alanine mutation in exon 4 (D90A). This
      mutation has been observed in dominant, recessive and apparently sporadically
      cases. SOD1(D90A/D90A) ALS cases have a very slow disease progression (>10
      years), raising the hypothesis that modifier genes linked to SOD1 ameliorate the
      phenotype of recessively inherited SOD1(D90A/D90A) mutations. Previous sequence
      analysis of a conserved haplotype region around the SOD1 gene did not reveal any
      functional polymorphisms within known coding or putative regulatory regions. In
      the current study we expanded the previous analyses by sequencing the entire SOD1
      conserved haplotypic region. Although many polymorphisms were identified, none of
      these variants explain the slowly progressive phenotype observed in patients with
      recessive SOD1(D90A) mutations. This study disproves the hypothesis that there is
      a tightly linked genetic protective factor specifically located close to the SOD1
      gene in SOD1(D90A) mediated ALS.

PMID- 19596402
TI  - MK801-induced activated caspase-3 exhibits selective co-localization with GAD67.
AB  - Blockade of the N-methyl-d-aspartate receptor (NMDAR) in postnatal day 7 (P7)
      rats can promote rapid and robust induction of the pro-apoptotic marker activated
      caspase-3 (AC3) and loss of the GABAergic marker GAD67 at P56. Thus, we
      hypothesized that NMDAR blockade-induced AC3 occurs in GAD67 positive cells at
      P7. To test this idea, we injected P7 rat pups with vehicle or MK801 and after 8h
      (peak of AC3 induction) we examined brain sections for both AC3 and GAD67.
      Compared to vehicle, MK801 profoundly induced AC3 in all brain regions examined
      but co-expression of GAD67 in the same cells was not observed. However, in brain
      regions where punctate (synaptic) GAD67 was abundant (for example, layer IV of
      the somatosensory cortex), AC3 was robust. These data suggest that whereas
      somatic expression of AC3 and GAD67 may be non-overlapping, areas that exhibit
      punctate GAD67 (and are high in synaptic turnover) may be more vulnerable to
      MK801 exposure.

PMID- 19596403
TI  - Grafted neural stem cells migrate to substantia nigra and improve behavior in
      Parkinsonian rats.
AB  - Neural stem cell (NSC) transplantation has the potential to treat
      neurodegenerative diseases such as Parkinson's disease (PD). In this study, we
      investigated the effect of transplanted NSCs in a PD animal model. NSCs isolated
      from the subventricular zone (SVZ) of E14 rats were cultured in vitro to produce
      neurospheres, which were subsequently infected with recombinant adeno-associated
      virus (rAAV(2)) expressing enhanced green fluorescent protein (EGFP). The PD
      animal model was established by unilateral injection of 6-hydroxydopamine (6
      OHDA) into the medial forebrain bundle (MFB) of Sprague-Dawley rats. Once the
      model was established, EGFP-expressing NSCs were transplanted into the substantia
      nigra pars compacta (SNc) or striatum of PD rats. We found that NSCs transplanted
      into either site significantly reduced apomorphine-induced circling behavior of
      PD rats. Pathological analysis revealed that the EGFP-expressing NSCs could be
      detected at both injection sites at 1, 2 and 4 months after transplantation. SNc
      transplanted cells dispersed within the SNc with a significant portion
      differentiated into tyrosine hydroxylase-positive neurons. Whereas cells
      transplanted into the striatum migrated ventrally and posteriorly towards the
      SNc. These results suggest that the 6-OHDA damaged brain area attracts grafted
      NSCs, which migrated from the striatum and survived for a long time in SNc,
      resulting in behavioral improvement of PD rats.

PMID- 19596404
TI  - The effect of leptin receptor deficiency and fasting on cannabinoid receptor 1
      mRNA expression in the rat hypothalamus, brainstem and nodose ganglion.
AB  - Despite ample evidence for the involvement of the endocannabinoid system in the
      control of appetite, food intake and energy balance, relatively little is known
      about the regulation of cannabinoid receptor 1 (CB(1)R) expression in respect to
      leptin signalling and fasting. In the present study, we examined CB(1)R mRNA
      levels in lean (Fa/?) and obese (fa/fa) male Zucker rats under basal and food
      restricted conditions. Using stereological sampling principles coupled with semi
      quantitative radioactive in situ hybridization we provide semi-quantitative
      estimates of CB(1)R mRNA expression in key appetite regulatory hypothalamic and
      brainstem areas, as well as in the nodose ganglia. Whereas no effect of fasting
      were determined on CB(1)R mRNA levels in the paraventricular (PVN) and
      ventromedial hypothalamic (VMH) nucleus, in the brainstem dorsal vagal complex or
      nodose ganglion of lean Zucker rats, CB(1)R mRNA levels were consistently
      elevated in obese Zucker rats pointing to a direct influence of disrupted leptin
      signalling on CB(1)R mRNA regulation.

PMID- 19596405
TI  - Abnormal white matter independent of hippocampal atrophy in amnestic type mild
      cognitive impairment.
AB  - Hippocampal atrophy is the key marker in the pathogenesis of Alzheimer's disease
      (AD), which is associated with white matter (WM) disruption. This type of WM
      disruption could partly explain AD-related pathology. However, relatively little
      attention has been directed toward WM disruption which may be independent of
      these fundamental gray matter (GM) changes in amnestic mild cognitive impairment
      (aMCI) which is associated with high risk of AD. To evaluate the differences of
      WM integrity between aMCI patients (N=32) and healthy controls (N=31), whole
      brain voxel-based methods were applied to diffusion tensor imaging. To explore
      the possible independence of WM changes from GM loss, an index of hippocampal
      atrophy was used to partial out GM effects. aMCI patients showed WM disruption in
      frontal lobe, temporal lobe, internal capsule, cingulate gyrus and precuneus. The
      findings supported the evidence of independent patterns of degeneration in WM
      tracts which may co-act in the WM pathological process of aMCI patients. As aMCI
      is a putatively prodromal syndrome to AD, these data may assist with a better
      understanding of WM pathological change associated with the development of AD.

PMID- 19596406
TI  - Short-time lower leg ischemia reduces plantar foot sensitivity.
AB  - The aim of this study was to investigate the effects of short-time blood flow
      occlusion on plantar foot vibration sensitivity of healthy young adults. 39
      subjects (20 female; 19 male) participated in the study. Blood flow reduction was
      evoked with a pneumatic tourniquet, placed about 10 cm above the popliteus
      cavity. Vibration thresholds (200 Hz) were measured at three anatomical locations
      of the plantar foot (heel, first metatarsal head and hallux) in three different
      cuff pressure conditions: baseline (0 mmHg), low (50 mmHg) and high (150 mmHg).
      Each pressure condition was held for 4 min prior to vibration threshold
      measurements. No reperfusion time was allowed between conditions. The results
      show a significant increase in vibration thresholds measured at all anatomical
      locations in the high pressure condition (150 mmHg), whereas low pressure (50
      mmHg) caused a significant threshold increase only at the hallux, compared to
      baseline (0 mmHg) measurements. Short-time blood flow occlusion seems to affect
      the afferent transmission of vibration stimuli from Vater-Pacini corpuscles,
      resulting in decreased plantar foot sensitivity. The present study provides an
      insight into initial adaptations caused by reduced blood flow in plantar foot
      sensitivity of healthy young adults.

PMID- 19596408
TI  - Vaccination with the Mycoplasma suis recombinant adhesion protein MSG1 elicits a
      strong immune response but fails to induce protection in pigs.
AB  - Mycoplasma suis is the unculturable pathogen of porcine infectious anemia. The
      study was aimed to determine the immunogenicity and protective efficacy of MSG1,
      an immunodominant adhesin of M. suis as the first vaccine candidate against M.
      suis. The results demonstrated that recombinant MSG1 and Escherichia coli
      transformants expressing MSG1 (E. coli_MSG1) induced a strong humoral and
      cellular immunity against M. suis. The induced antibodies were found to be
      functionally active as confirmed by an in vitro adhesion inhibition assay. Both,
      IgG1 and IgG2 antibodies were induced, but E. coli_MSG1 immune response was
      characterized by a significantly higher IgG1 antibody production. Both vaccine
      candidates failed to protect against M. suis challenge. However, E. coli_MSG1
      vaccination has a considerable effect on the severity of the disease as shown by
      higher post-challenge hemoglobin and hematocrit values in comparison to control
      groups. This indicated that a high IgG1 antibody titer is negatively connected
      with severity of M. suis-induced anemia. Furthermore, the induction of
      monospecific anti-MSG1 antibodies by both vaccine candidates clearly allows for
      the differentiation between infected and vaccinated animals (DIVA principle).
      Overall, the importance of MSG1 as potential vaccine candidate remains to be
      established. Future studies will evaluate the conditions (i.e. adjuvant,
      vaccination scheme, and application route) to optimize the effects of E.
      coli_MSG1 vaccines.

PMID- 19596409
TI  - Girls may have lower levels of maternal measles antibodies and higher risk of
      subclinical measles infection before the age of measles vaccination.
AB  - BACKGROUND: Previous studies have suggested that girls may have lower maternal
      measles antibody levels than boys. Girls might therefore be more likely to
      contract measles infection before the normal age of measles vaccination at 9
      months of age. METHODS: In connection with a clinical trial of different measles
      vaccination strategies, we collected pre-measles vaccination blood samples at 4.5
      months of age from two subgroups of children. Samples from these children were
      used to assess possible differences in maternal antibody levels for boys and
      girls. At 9 months of age another subgroup of children was sampled before the
      normal measles vaccination; these samples were used to assess the frequency of
      subclinical measles infection among boys and girls. RESULTS: We determined
      measles-specific antibody levels for 812 children at 4.5 months of age and for
      896 children at 9 months of age. At 4.5 months of age girls were less likely to
      have protective maternal antibody levels, the male-female ratio for protective
      antibody level being 1.23 (1.00-1.51). Among children sampled at 9 months of age,
      girls were more likely to have protective levels, the female-male ratio for
      having protective antibody levels being 1.65 (0.98-2.78) (p=0.054) and the
      geometric mean titre was significantly higher for girls (p=0.007). Children who
      lived in houses with known measles cases were more likely to have protective
      levels at 9 months of age even though they had not reported measles infection.
      Since we had excluded children with known measles infection, girls may have been
      more likely to have had subclinical measles infection. Combining clinical and
      possible subclinical measles infection, girls tended to be more likely than boys
      to contract measles infection before 9 months of age, the RR being 1.36 (0.97
      1.90). CONCLUSIONS: Girls lost maternal measles antibodies more rapidly than boys
      and well before 9 months of age. They may be more likely to contract subclinical
      measles infection before the current age of measles vaccination.

PMID- 19596407
TI  - Oral vaccination with LcrV from Yersinia pestis KIM delivered by live attenuated
      Salmonella enterica serovar Typhimurium elicits a protective immune response
      against challenge with Yersinia pseudotuberculosis and Yersinia enterocolitica.
AB  - The use of live recombinant attenuated Salmonella vaccines (RASV) synthesizing
      Yersinia proteins is a promising approach for controlling infection by Yersinia
      species. In this study, we constructed attenuated Salmonella strains which
      synthesize a truncated form of LcrV, LcrV196 and evaluated the immune response
      and protective efficacy elicited by these strains in mice against two other major
      species of Yersinia: Yersinia pseudotuberculosis and Yersinia enterocolitica.
      Surprisingly, we found that the RASV strain alone was sufficient to afford nearly
      full protection against challenge with Y. pseudotuberculosis, indicating the
      likelihood that Salmonella produces immunogenic cross-protective antigens. In
      contrast, lcrV196 expression was required for protection against challenge with
      Y. enterocolitica strain 8081, but was not sufficient to achieve significant
      protection against challenge with Y. enterocolitica strain WA, which expressed a
      divergent form of lcrV. Nevertheless, we are encouraged by these findings to
      continue pursuing our long-term goal of developing a single vaccine to protect
      against all three human pathogenic species of Yersinia.

PMID- 19596410
TI  - High tetanus and diphtheria antitoxin concentrations in Finnish adults--time for
      new booster recommendations?
AB  - The tetanus and diphtheria vaccination programme in Finland has been running for
      50 years. After primary doses, tetanus boosters have been offered to men in
      military service and decennial boosters recommended for all through the adult
      life. For 30 years a diphtheria booster was only offered to men in the military
      service. Not until 1989 diphtheria-tetanus (dT) and diphtheria (d) booster
      vaccines for adolescence and adults were introduced. In this study serum samples
      of 990 subjects from 30 years of age, participating in a population survey in
      2000-2001, were used to assess the tetanus and diphtheria antitoxin
      concentrations. More than 70% of the adults up to 50 years of age were fully
      protected (antitoxin concentrations >0.1 IU mL) against tetanus and diphtheria.
      Of these adults more that 76% had antitoxin concentrations >1 IU/mL against
      tetanus, indicating long-term protection but also an increased risk for
      hyperimmunisation. A comparison of this study and two immunogenicity studies
      conducted in Finland in 1987-1988 and 1995-1996 shows the impact of an active
      decennial dT adult booster programme in a country with a high primary tetanus and
      diphtheria vaccination coverage in infants since the 1950s. Recommendations for
      limited decennial boosters by increase the time interval between dT boosters up
      to 20 years as suggested by this study and also studies performed, e.g., in
      Denmark and Portugal should be considered. Finnish adults born before 1930
      should, however, still be vaccinated with decennial boosters, especially against
      tetanus.

PMID- 19596412
TI  - Immune thrombocytopenic purpura reactivation after tick-borne encephalitis
      vaccination.

PMID- 19596411
TI  - Protection of mice from Brucella infection by immunization with attenuated
      Salmonella enterica serovar typhimurium expressing A L7/L12 and BLS fusion
      antigen of Brucella.
AB  - This study describes the potential use of attenuated Salmonella enterica serovar
      Typhimurium Strains (S. typhimurium) to express and deliver a L7/L12 and BLS
      fusion antigen of Brucella as a vaccination strategy to prevent Brucella
      infection in mice. S. typhimurium X4072 that contained a pTrc99A-BLS-L7/L12
      plasmid, designated X4072bl, can deliver a L7/L12 and BLS fusion antigen
      expressed by the bacterium itself, while S. typhimurium X4550 that contained an
      asd-pVAX1-BLS-L7/L12 (asd-pBL) plasmid, designated X4550bl, can deliver the
      antigen to be expressed in target eukaryotic cells. When orally administered to
      BALB/c mice, both attenuated carrier strains were able to elicit mucosal and
      systemic immunity, which induced protection against B. abortus 544 infection in
      mice. The immunogenicity and protective efficacy of X4072bl and X4550bl were
      compared with a recombinant BLS-L7/L12 fusion protein vaccine (rBL) and a pVAX1
      BLS-L7/L12 DNA vaccine (pBL) in this study. When rBL and pBL were intramuscularly
      injected into mice, both vaccines could also elicit comparable humoral and
      cellular immune responses, but not mucosal immunity, which therefore induced
      lower protection. Taken together, Salmonella-based subunit vaccines are a
      promising vaccine strategy in the prevention of Brucella infection.

PMID- 19596413
TI  - Enhancement of antitumor immune response by targeted interleukin-12 electrogene
      transfer through antiHER2 single-chain antibody in a murine bladder tumor model.
AB  - Interleukin-12 (IL-12), despite exerting antitumor activity, has limited
      therapeutic uses due to its systemic toxicity. Since HER2 (also known as ErbB-2,
      neu, and HER2/neu) is frequently overexpressed on cancer cells, HER2-targeted
      delivery of IL-12 to tumors may be a promising strategy for enhancing antitumor
      immunity. Here we showed that intramuscular electrogene transfer of an expression
      vector encoding a fusion protein antiHER2scFv-IL12, which consists of antiHER2
      single-chain variable fragment (scFv) and single-chain IL-12, significantly
      retarded tumor growth and prolonged the survival in a syngeneic bladder tumor
      model. Elevated IL-12 and interferon-gamma (IFN-gamma) levels, increased
      infiltration of CD4(+) and CD8(+) T cells, and reduced vascular endothelial
      growth factor (VEGF) expression in the tumors, as well as enhanced cytolytic
      activity of splenocytes were noted in the treated mice. Our results suggest that
      this approach may be effective for the treatment of HER2-overexpressing tumors.

PMID- 19596414
TI  - Long lasting immunity in chickens induced by a single shot of influenza vaccine
      prepared from inactivated non-pathogenic H5N1 virus particles against challenge
      with a highly pathogenic avian influenza virus.
AB  - An influenza vaccine was prepared from inactivated whole particles of the non
      pathogenic strain A/duck/Hokkaido/Vac-1/04 (H5N1) virus using an oil adjuvant
      containing anhydromannitol-octadecenoate-ether (AMOE). The vaccine was injected
      intramuscularly into five 4-week-old chickens, and 138 weeks after vaccination,
      they were challenged intranasally with 100 times 50% chicken lethal dose of the
      highly pathogenic avian influenza (HPAI) virus A/chicken/Yamaguchi/7/04 (H5N1).
      All 5 chickens survived without exhibiting clinical signs of influenza, although
      2 days post-challenge, 3 vaccinated chickens shed limited titres of viruses in
      laryngopharyngeal swabs.

PMID- 19596415
TI  - Identification of HLA class II H5N1 hemagglutinin epitopes following subvirion
      influenza A (H5N1) vaccination.
AB  - Prophylactic immunization against influenza infection requires CD4+ T-helper cell
      activity for optimal humoral and cellular immunity. Currently there is one FDA
      approved H5N1 subvirion vaccine available, although stockpiles of this vaccine
      are insufficient for broad population coverage and the vaccine has only
      demonstrated modest immunogenicity. Specific activation of CD4+ T-helper cells
      using class II H5N1 HA peptide vaccines may be a useful component in immunization
      strategy and design. Identification of HLA class II HA epitopes was undertaken in
      this report by obtaining PBMCs from volunteers previously immunized with an H5N1
      inactivated subvirion vaccine, followed by direct ex vivo stimulation of CD4+ T
      cells against different sources of potential HA class II epitopes. In the 1st
      round of analysis, 35 donors were tested via IFN-gamma ELISPOT using pools of
      overlapping HA peptides derived from the H5N1 A/Thailand/4(SP-528)/2004 virus,
      recombinant H5N1 (rHA) and inactivated H5N1 subvirion vaccine. In addition, a
      series of algorithm-predicted epitopes coupled with the Ii-Key moiety of the MHC
      class II-associated invariant chain for enhanced MHC class II charging were also
      included. Specific responses were observed for all 20 peptide pools, with 6-26%
      of vaccinated individuals responding to any given pool (donor response frequency)
      and a magnitude of response ranging from 3- to >10-fold above background levels.
      Responses were similarly observed with the majority of algorithm-predicted
      epitopes, with a donor response frequency of up to 29% and a magnitude of
      response ranging from 3-10-fold (11/24 peptides) to >10-fold above background
      (7/24 peptides). PBMCs from vaccine recipients that had detectable responses to
      H5N1 rHA following 1st round analysis were used in a 2nd round of testing to
      confirm the identity of specific peptides based on the results of the 1st
      screening. Sixteen individual HA peptides identified from the library elicited
      CD4+ T cell responses between 3- and >10-fold above background, with two peptides
      being recognized in 21% of recipients tested. Eight of the putative MHC class II
      epitopes recognized were found in regions showing partial to significant sequence
      homology with New Caledonia H1N1 influenza HA, while eight were unique to H5N1
      HA. This is the first study to identify H5N1 HA epitope-specific T cells in
      vaccine recipients and offers hope for the design of a synthetic peptide vaccine
      to prime CD4+ T-helper cells. Such a vaccine could be used to provide at least
      some minimal level of H5N1 protection on its own and/or prime for a subsequent
      dose of a more traditional but supply-limited vaccine.

PMID- 19596416
TI  - Construction and evaluation of DNA vaccines encoding Edwardsiella tarda antigens.
AB  - Edwardsiella tarda is an opportunistic pathogen that can infect humans, animal,
      and fish. Two E. tarda antigens, Eta6 and FliC, which are homologues to an ecotin
      precursor and the FliC flagellin, respectively, were identified by in vivo
      induced antigen technology from a pathogenic E. tarda strain isolated from
      diseased fish. When used as a subunit vaccine, purified recombinant Eta6 was
      moderately protective against lethal challenge of E. tarda in a Japanese flounder
      model, whereas purified recombinant FliC showed no apparent immunoprotectivity.
      Similarly, DNA vaccines based on eta6 and fliC in the form of plasmids pEta6 and
      pFliC induced, respectively, moderate and marginal protection against E. tarda
      infection. To improve the vaccine efficacy of eta6, a chimeric DNA vaccine, pCE6,
      was constructed, which encodes Eta6 fused in-frame to FliC. pCE6 was found to
      induce significantly higher level of protection than pEta6. Likewise, another
      chimeric DNA vaccine, pCE18, which expresses FliC fused to a previously
      identified E. tarda antigen Et18, elicited significantly stronger protective
      immunity than the DNA vaccine based on et18 alone. Fish immunized with pEta6 and
      pCE6 produced specific serum antibodies and exhibited significantly enhanced
      expression of the genes encoding elements that are involved in both innate and
      adaptive immune responses. Furthermore, the induction magnitudes of most of these
      genes were significantly higher in pCE6-vaccinated fish than in pEta6-vaccinated
      fish.

PMID- 19596417
TI  - Identification of a surface protective antigen, HP0197 of Streptococcus suis
      serotype 2.
AB  - Streptococcus suis serotype 2 (SS2) is a porcine and human pathogen with adhesive
      and invasive properties. As traditional inactive vaccine has obvious
      shortcomings, to identify protective antigens would undoubtedly contribute to the
      development of novel vaccines. HP0197 has been identified as immunogenic protein
      in the previous study but its protective efficacy was not clear. In the present
      study, the purified recombinant HP0197 protein could elicit a significant humoral
      antibody response and could confer significant protection against challenge with
      lethal dose of SS2 in mice and pigs. In addition, the hyperimmune sera against
      HP0197 could efficiently kill the bacteria in the opsonized phagocytosis test and
      conferred significant protection against SS2 infection in the experiment of
      passive immunization. The present study suggests with strong evidence that the
      identified protective antigen would be a novel and an effective vaccine candidate
      for SS2.

PMID- 19596418
TI  - Early life DNA vaccination with the H gene of Canine distemper virus induces
      robust protection against distemper.
AB  - Young mink kits (n=8) were vaccinated with DNA plasmids encoding the viral
      haemagglutinin protein (H) of a vaccine strain of Canine distemper virus (CDV).
      Virus neutralising (VN) antibodies were induced after 2 immunisations and after
      the third immunisation all kits had high VN antibody titres. The VN antibody
      titres remained high for more than 4 months and the mink were protected against
      viraemia, lymphopenia, clinical disease and changes in the percentage of IFN
      gamma producing peripheral blood leucocytes after challenge inoculation with a
      recent wild type strain of CDV. Essentially, these results demonstrate that early
      life DNA vaccination with the H gene of a CDV vaccine strain induced robust
      protective immunity against a recent wild type CDV.

PMID- 19596420
TI  - Attitudes toward HPV vaccination among parents of adolescent girls in Mysore,
      India.
AB  - This study investigates attitudes toward human papillomavirus (HPV) vaccination
      among parents of adolescent girls in Mysore, India. Seven focus group discussions
      were held among parents of adolescent girls stratified by sex, religion and
      region to explore attitudes about cervical cancer and HPV vaccination. The study
      found that while parents have limited knowledge about HPV or cervical cancer,
      most are still highly accepting an HPV vaccine. In addition, high acceptability
      levels appear to reflect positive attitudes toward the government universal
      immunization program in general, rather than to the HPV vaccine in particular.
      The results highlight the need for additional education and health promotion
      regarding HPV and cervical cancer prevention in India.

PMID- 19596421
TI  - "Anti-HPV vaccination: a review of recent economic data for Italy.".

PMID- 19596419
TI  - Plasmodium berghei HAP2 induces strong malaria transmission-blocking immunity in
      vivo and in vitro.
AB  - Fertilization in Plasmodium is a complex process that occurs in the gut of the
      female Anopheles mosquito upon uptake of a bloodmeal. It requires the emergence
      of the gametocyte from the RBC and release of eight flagellate male gametes from
      each male cell, and subsequent fertilization of a similarly emerged immotile
      extracellular female macrogamete. Previous studies have demonstrated that
      antibodies against male gamete surface proteins ingested from the blood of an
      infected and immunized host inhibit parasite transmission. Gene disruption
      studies in Plasmodium berghei and complimentary studies on the green alga
      Chlamydomonas have shown that a conserved male gamete sterility gene, HAP2, is
      essential for fusion of male and female gametes. Genetic disruption of the HAP2
      locus revealed that parasite fertilization is prevented, yet hap2 KO male gametes
      still retained the ability to form tight pre-fusion membrane attachments with
      females.We demonstrate that heterologous expression of the P. berghei HAP2
      protein in Escherichia coli, and subsequent immunization of rabbits, has produced
      anti-sera that react specifically with recombinant HAP2, and with the native
      protein on the male gamete. Additionally, anti-HAP2 sera reduces in vitro
      formation of ookinetes by up to 81%, and, using standard membrane feeding assays,
      reduces oocyst burden within the mosquito host by up to 81.1%, and prevalence of
      in vivo infection by up to 34%. Inhibition is dose dependent. These results
      indicate that HAP2 should be considered as a potential target for any future anti
      malarial transmission-blocking vaccine.

PMID- 19596423
TI  - Adolescent health care use: investigating related determinants in Greece.
AB  - The frequency of health care use is crucial for adolescent well-being and health
      systems. The present study was the first to test a set of variables in a
      representative sample of Greek adolescents in order to identify factors that
      predict health care use and contribute to improving health service planning.
      Questionnaires were administered to a random sample of adolescents (N=1 194) aged
      11-18 years and their parents (N=973) in 2003. Data from 894 participants with
      full data were analyzed. Parents' education, adolescents' chronic health needs,
      physical well-being and emotional/behavioural problems as well as parent-child
      relationship were independent predictors of health care use, although some
      factors, such as gender, age, type of residence, family affluence, social support
      and parental health status that previous research identified as predictors were
      not confirmed. Beyond the need of health care, other factors also play an
      important role in the utilization of health services by adolescents and their
      families.

PMID- 19596422
TI  - Ultrastructural characterization of tooth-biomaterial interfaces prepared with
      broad and focused ion beams.
AB  - Current available techniques for transmission electron microscopy (TEM) of tooth
      biomaterial interfaces are mostly ineffective for brittle phases and impair
      integrated chemical and morphological characterization. OBJECTIVES: The aims of
      this study were (1) to determine the applicability of new focused ion beam (FIB)
      and broad ion beam (BIB) techniques for TEM preparation of tooth-biomaterial
      interfaces; (2) to characterize the interfacial interaction with enamel and
      dentin of a conventional glass-ionomer (Chemfil Superior, DeTrey Dentsply,
      Germany), a 2-step self-etch (Clearfil SE, Kuraray, Japan) and a 3-step etch-and
      rinse (OptiBond FL, Kerr, USA) adhesives; and (3) to characterize clinically
      relevant interfaces obtained from actual Class-I cavities. METHODS: After bonding
      to freshly extracted human third molars, non-demineralized and non-stained
      sections were obtained using the FIB/BIB techniques and examined under TEM.
      RESULTS: The main structures generally disclosed in conventional ultramicrotomy
      samples were recognized in FIB/BIB-based ones. There were not any major
      differences between FIB and BIB concerning the resulting ultrastructural
      morphology. FIB/BIB-sections enabled to clearly resolve sub-micron hydroxyapatite
      crystals on top of hard tissues and the interface between matrix and filler in
      all materials, even at nano-scale. Some investigated interfaces disclosed areas
      with a distinct "fog" or "melted look", which is probably an artifact due to
      surface damage caused by the high-energy beam. Interfaces with enamel clearly
      disclosed the distinct "keyhole" shape of enamel rods sectioned at 90 degrees ,
      delimited by a thin electron-lucent layer of inter-rod enamel. At regions where
      enamel crystals ran parallel with the interface, we observed a lack of
      interaction and some de-bonding along with interfacial void formation.
      SIGNIFICANCE: The FIB/BIB methods are viable and reliable alternatives to
      conventional ultramicrotomy for preparation of thin sections of brittle and thus
      difficult to cut biomaterial-hard tissue interfaces. They disclose additional
      ultrastructural information about both substrates and are more suitable for
      advanced analytic procedures.

PMID- 19596424
TI  - Parental guidance about drinking: relationship with teenage psychoactive
      substance use.
AB  - Parental guidance concerning alcohol was explored using data from a 2007 survey
      of 2179 UK school students aged 15 and 16 years. Cluster analysis based on
      questions about parental advice was used to establish seven student groups.
      Associations between groups, other family background and psychoactive substance
      use variables were explored. Substance use was least common amongst students
      whose parents discouraged drinking and those who claimed to have received no
      parental guidance. The heaviest substance users were teenagers from families with
      more favourable, tolerant attitudes to alcohol and intoxication and among
      students who failed to answer the questions about parental guidance. These scored
      highly on cannabis and other drug use. The cluster in which there was
      comprehensive discussion with the parents about alcohol use had an intermediate
      position in relation to substance use. In logistic regressions parental guidance
      was consistently associated with substance use with several other background
      variables controlled.

PMID- 19596425
TI  - Compound Cordyceps TCM-700C exhibits potent hepatoprotective capability in animal
      model.
AB  - A herbal preparation "Compound Codyceps-TCM-700C (CC-700C)" was tested for
      hepatoprotective effect against the carbon tetrachloride induced liver damages in
      Sprague-Dawley rat model for a period of 6-weeks. Two dosage levels of CC-700C,
      respectively 286.2 mg/kg-bw (L-TCM) and 2862 mg/kg-bw (H-TCM), and a positive
      control Silymarin (Sigma) were used to compare their therapeutic effect. Both CC
      700C's and Silymarin showed nontoxic in nature, as evidenced by body weight gain,
      organ weights and appearance including liver, spleen, and kidney. The activities
      of aspartate aminotransferase (AST) and alanine-aminotransferase (ALT) were more
      effectively suppressed by CC-700C than Silymarin. In addition, all levels of
      serum bilirubin, serum albumin, triglyceride (TG), total cholesterol (TC),
      platelet count (PLT), and prothrombin time (PT) except TG were shown effectively
      restored to normal values by CC-700C and Silymarin. Moreover, although levels of
      glutathione (GSH), glutathione reductase (GSH-Rd), and superoxide dismutase (SOD)
      were equally maintained by these three preparations, glutathione peroxidase (GSH
      Px) was suppressed only by H-TCM, and SOD only by Silymarin. In contrast, the
      activity of catalase efficiently recovered to control level on administration of
      CC-700C, being far better than Silymarin. Finally the liver collagen content, an
      indication of fibrosis, was also significantly suppressed by CC-700C, better
      effect was by L-TCM, but both levels were superior to Silymarin. Conclusively,
      the herbal preparation "Compound Cordyceps TCM-700C" is a potent hepatoprotective
      preparation. For therapeutic use, a dosage of 286.2 mg/kg-bw would be
      sufficiently effective.

PMID- 19596426
TI  - Dogs discriminate between barks: the effect of context and identity of the
      caller.
AB  - In the present study we explored whether dogs (Canis familiaris) are able to
      discriminate between conspecific barks emitted in different contexts recorded
      either from the same or different individuals. Playback experiments were
      conducted with dogs using barks as stimuli in a habituation-dishabituation
      paradigm. Barks were recorded in two contexts (stranger at the fence and when the
      dog was left alone) from different individuals. We found that dogs distinguished
      between barks emitted in these two contexts and were also able to discriminate
      between different individuals which were barking in the same context. These
      findings suggest that dog bark may carry context- and individual-specific
      information for the conspecifics.

PMID- 19596427
TI  - Quercetin protects embryonic chicken spermatogonial cells from oxidative damage
      intoxicated with 3-methyl-4-nitrophenol in primary culture.
AB  - Diesel exhaust particles (DEP) are considered to be one of the most important air
      pollutants. In this study, the protective effect of quercetin, an antioxidant
      flavonoid, on oxidative damage of testicular cells was studied by analysis of the
      intracellular antioxidant system of embryonic chickens after treatment with 3
      methyl-4-nitrophenol (PNMC) derived from DEP. Testicular cells from 18-day-old
      embryos were cultured in serum-free McCoys'5A medium and challenged with PNMC
      (10(-7) to 10(-5)M) alone or in combinations with quercetin (1.0 microg/ml) for
      48h. Results showed that exposure to PNMC (10(-5)M) induced condensed nuclei and
      vacuolated cytoplasm, a decrease in testicular cell viability and spermatogonial
      cell number. Exposure to PNMC induced lipid peroxidation by an elevation of
      thiobarbituric acid reactive substances as well as decreasing glutathione
      peroxidation activity and superoxide dismutase activity. However, simultaneous
      supplementation with quercetin restored these parameters to the similar levels as
      the control. PNMC is therefore concluded to have induced the oxidative stress of
      the spermatogonial cells, which can be attenuated by combined quercetin
      treatment. Our results support the therapeutic use of quercetin in the prevention
      or treatment of the reproductive toxicity by environmental toxicant PNMC.

PMID- 19596428
TI  - Understanding the effect of lactose particle size on the properties of DPI
      formulations using experimental design.
AB  - Medicines for delivering therapeutic agents to the lung as dry powders primarily
      consist of a carrier and a micronised active pharmaceutical ingredient (API). The
      performance of an inhaled formulation will depend on a number of factors amongst
      which the particle size distribution (PSD) plays a key role. It is suggested that
      increasing the number of fine particles in the carrier can improve the
      aerosolisation of the API. In addition the effect of PSD upon a bulk powder is
      also broadly understood in terms of powder flow. Other aspects of functionality
      that different size fractions of the carrier affect are not clearly understood;
      for example, it is not yet clearly known how different size fractions contribute
      to the different functionalities of the carrier. It is the purpose of this
      investigation to examine the effects of different lactose size fractions on fine
      particle dose, formulation stability and the ability to process and fill the
      material in the preferred device. In order to understand the true impact of the
      size fractions of lactose on the performance of dry powder inhaled (DPI)
      products, a statistically designed study has been conducted. The study comprised
      various DPI blend formulations prepared using lactose monohydrate carrier systems
      consisting of mixtures of four size fractions. Interactive mixtures were prepared
      containing 1% (w/w) salbutamol sulphate. The experimental design enabled the
      evaluation of the effect of lactose size fractions on processing and performance
      attributes of the formulation. Furthermore, the results of the study demonstrate
      that an experimental design approach can be used successfully to support dry
      powder formulation development.

PMID- 19596429
TI  - Nanoscale thermal analysis of pharmaceutical solid dispersions.
AB  - Formation of a solid solution of a drug in a water-soluble polymer is one of the
      primary techniques used to improve the dissolution rate and thus bioavailability
      of a poorly water-soluble drug. Understanding and detecting the state of the drug
      inside such a polymer matrix is critically important since issues such as drug
      stability, safety and efficacy can be greatly affected. In this study, two model
      formulations were prepared containing low and high levels of drug content. The
      heterogeneity of the formulations has been investigated using a novel nanothermal
      analysis technique. This technique has demonstrated a promising capability for
      imaging and quantitatively characterising the nanoscale properties of solid
      dispersion formulations.

PMID- 19596430
TI  - Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical
      characterisation and permeability through Caco-2 cell monolayers.
AB  - In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a
      mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was
      investigated. The size, zeta potential and melatonin loading of the
      lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid
      S45, S75 and S100) and chitosan content in the preparation. The NPs were
      characterised by mean diameter and zeta potential ranging between 121.6 and 347.5
      nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative
      charge and chitosan content in the preparation. Melatonin loadings were up to
      7.1%. All NPs were characterised by prolonged release profiles with an initial
      burst (approximately 25%), followed by a slow release phase. Approximately 60-70%
      of melatonin was released in 4h. The permeability of melatonin was investigated
      using Caco-2 cells as an in vitro model of the epithelial barrier. Melatonin
      permeability from an NP suspension prepared with Lipoid S45 lecithin and a
      lecithin-to-chitosan weight ratio (L/C) of 20:1 (sample C2) was significantly
      improved compared to the permeability of melatonin from the solution (P<0.001)
      and from all other NPs investigated (P<0.05). The results obtained by the cell
      viability studies (MTT and LDH leakage assays) showed that C2 NP suspension did
      not induce plasma membrane damage or decrease cell viability and could be safely
      applied to Caco-2 cells in the concentration range tested (<400 microg/ml).

PMID- 19596432
TI  - Kynurenic acid in blood and bone marrow plasma of monoclonal gammopathy of
      undetermined significance (MGUS) and multiple myeloma (MM) patients.
AB  - Increased levels of kynurenic acid (KYNA) have been detected in patients with
      neurological, autoimmune and tumor diseases. The aim of this paper was to
      determine KYNA levels in the blood and bone marrow plasma of MGUS and MM patients
      and to find out common events which are characteristic for both pathological
      stages and correlates with diagnostic markers of MGUS and MM. We also examined
      whether bone marrow stromal cells (BMSCs) and MM cells could produce KYNA. The
      levels of KYNA present in plasma and in cell culture media were examined by HPLC.
      An increased level of KYNA was detected in the blood and marrow plasma of MGUS
      patients and in the blood plasma of the MM group. In the MM group, the blood KYNA
      level was the highest in patients with monoclonal IgG protein and with free light
      chains of immunoglobulins and correlated positively with blood levels of
      creatinine and urea. In the MGUS group, KYNA correlated positively with the C
      reactive protein (CRP) level, and in both groups KYNA correlated positively with
      the beta2-microglobulin. We detected KYNA production in BMSCs of control and MM
      patients and by two myeloma cell lines used in the experiments. The results
      suggest that the increased KYNA level in MGUS patients was mainly caused by a
      dysfunction of the immune system, as it correlated positively with CRP and beta2
      microglobulin levels. In MM patients, the increased KYNA level may have been a
      result of a dysfunction of the immune system, KYNA production by myeloma cells,
      and decreased KYNA excretion by kidneys.

PMID- 19596431
TI  - Significance of four MRD markers in MRD-based treatment strategy for childhood
      acute lymphoblastic leukemia.
AB  - Newly diagnosed children with ALL (n=32) were treated on a protocol incorporating
      minimal residual disease (MRD)-based treatment decisions. MRD was monitored at 4
      time points by semi-quantitative PCR detection of antigen receptor gene
      rearrangement, flow cytometry, quantitative RT-PCR detection of chimeric gene
      transcripts and overexpressed WT1 mRNA. Four patients positive for MRD at week 5
      were treated with an intensified regimen. Median follow-up was 5.0 years (range
      3.8-6.6 years) with a 4-year event-free survival rate of 93.8+/-4.3%. This MRD
      based treatment strategy seems to be highly successful and may improve the
      outcomes of children with ALL. A large study is warranted.

PMID- 19596433
TI  - An unexpected effect of 5-MCA-NAT in chick retinal development.
AB  - Luzindole is an unselective antagonist of the melatonin receptors and melatonin's
      other binding sites, although some exceptions have been observed in chick retinal
      neurodevelopment, where this unselective antagonist does not block melatonin's
      inhibitory effect on the adenylate cyclase enzyme, probably due to the presence
      of some other melatonin receptor(s) or binding site(s). The present study
      investigated the modulation of cyclic adenosine 3'-5'-monophosphate (cAMP) levels
      via MT3 melatonin-binding sites, located within the QR2 (dihydronicotinamide
      riboside: quinone oxidoreductase 2) enzyme, by observing the response to
      luzindole. Embryonic and post-hatch retinas, incubated with a selective agonist
      for the MT3 melatonin-binding site 5-methoxycarbonylamino-N-acetyltryptamine (5
      MCA-NAT, 10 or 100 nM), had an increase in cAMP accumulation relative to control
      retinas. Luzindole (5microM) inhibited the 5-MCA-NAT stimulatory effect at all
      ages tested. The agonist 5-MCA-NAT enhanced the melatonin inhibitory effect on
      cAMP levels stimulated by forskolin (5microM), but not the stimulatory forskolin
      effect. The results suggest that MT3 melatonin-binding sites are present in
      embryonic and post-hatch chick retinas and that luzindole more selectively blocks
      the 5-MCA-NAT effect on cAMP accumulation than it blocks the melatonin inhibitory
      effect via G protein-coupled receptors in chick retinal neurodevelopment.

PMID- 19596434
TI  - Sexual and physical revictimization among victims of severe childhood sexual
      abuse.
AB  - OBJECTIVE: This 15-year prospective, longitudinal study examines adolescent and
      young-adult female self-reports of traumatic sexual and physical experiences
      occurring subsequent to substantiated childhood sexual abuse-revictimizations
      (N=89). METHOD: These incidences were contrasted to sexual and physical
      victimizations reported by a group of non-abused comparison females (N=90).
      RESULTS: Abused females were almost twice as likely to have experienced sexual
      revictimization (odds=1.99+/-2.79, p<.05), and physical revictimization
      (odds=1.96+/-2.58, p<.05) as compared to victimization rates reported by
      comparison females. Abused females' revictimizations were also more likely to
      have been perpetrated by older, non-peers and characterized by physical injury
      than were victimizations reported by comparison females. CONCLUSION: Early
      childhood sexual abuse may provide information regarding the level of risk for
      recurrent sexual and physical victimization.

PMID- 19596435
TI  - EstA protein, a novel virulence factor of Streptococcus pneumoniae, induces
      nitric oxide and pro-inflammatory cytokine production in RAW 264.7 macrophages
      through NF-kappaB/MAPK.
AB  - In the present study we characterized the molecular mechanism by which esterase A
      (EstA) protein, a novel virulence factor of Streptococcus pneumoniae induces
      inflammation. Stimulation of RAW 264.7 macrophages with purified EstA protein
      induced the expression of inducible nitrogen oxide synthase (iNOS) mRNA and
      nitrogen oxide (NO) production in a concentration-dependent manner. Inhibitors of
      iNOS, NF-kappaB, p38 and ERK 1/2 MAPK pathways significantly decreased (50-78%)
      EstA-induced NO production. Similarly, EstA induced TNF-alpha, IL-1 beta and IL-6
      mRNA expression in RAW 264.7 macrophages in a dose-dependent manner, and pre
      treatment of the cell cultures with specific NF-kappaB, p38 and ERK 1/2 MAPK
      pathway inhibitors significantly decreased EstA-induced TNF-alpha, IL-1 beta and
      IL-6 protein production. Furthermore, immunoblot analysis revealed the
      degradation of the inhibitory kappa B (IKB-alpha) in response to EstA
      stimulation. Taken together, our data suggests that EstA protein is a novel
      inducer of NO and pro-inflammatory cytokines by activating the NF-kappaB, p38 and
      ERK 1/2 MAPK pathways during inflammatory responses. Future studies on the
      upstream protein kinases of the MAPK/NF-kappaB pathways and the kinetics of
      cytokine production will provide further details into the mechanism of EstA
      induced inflammatory response.

PMID- 19596436
TI  - Effects of 5-acetyl(carbamoyl)-6-methylsulfanyl-1,4-dihydropyridine-5
      carbonitriles on rat liver mitochondrial function.
AB  - It is increasingly recognised that mitochondria are potential targets to
      pharmacological and toxicological actions of membrane-active agents, including
      some 1,4-dihydropyridines derivatives (DHPs). The 5-acetyl(carbamoyl)-6
      methylsulfanyl-1,4-dihydropyridine-5-carbonitriles (OSI-1146, OSI-3701, OSI-3761,
      and OSI-9642) is a new group of DHPs with minor differences on the molecular
      structure. It has also been shown that OSI-1146 displays cardiovascular,
      antioxidant, and antiradical activities, whereas OSI-3701 and OSI-3761 display
      hepatoprotective activity. Due to their protective properties, this group of DHPs
      may be potentially useful for the treatment of several pathological processes,
      including those associated with oxidative stress. However, the cellular targets
      for their pharmacological actions have not been investigated. The presented
      study, using isolated rat liver mitochondria was designed to investigate if
      mitochondria are a cellular target for the pharmacological and/or toxicological
      actions of these new group of DHPs. We studied the direct influence of these DHPs
      on rat liver mitochondrial function [bioenergetics, membrane permeability
      transition (MPT), and oxidative stress]. It was shown that OSI-1146, OSI-3761,
      and OSI-9642, in the concentration range of up to 200 microM, interfered with
      mitochondrial bioenergetics by affecting complexes I and II of the mitochondrial
      respiratory chain, the ATPase activity, and mitochondrial inner membrane
      permeability to protons. However, the effects of OSI-1146 were higher than those
      of OSI-3761 and OSI-9642. The remaining compound, OSI-3701, had no effect on the
      bioenergetic parameters tested. All the compounds increased the susceptibility of
      mitochondria to MPT, but, OSI-3701, not affecting the bioenergetic parameters,
      was the most potent. Moreover, all the compounds protected mitochondria against
      lipid peroxidation induced by the oxidant pair ADP/Fe(2+), but OSI-1146 was also
      the most potent. In conclusion, our results indicate that mitochondria are the
      potential intracellular targets for both protective and toxicological actions of
      the DHP compounds studied, suggesting that the potential use of these compounds
      as therapeutic agents should carefully consider their toxic effects to
      mitochondria.

PMID- 19596437
TI  - Multiple Choice Knapsack Problem: example of planning choice in transportation.
AB  - Transportation programming, a process of selecting projects for funding given
      budget and other constraints, is becoming more complex as a result of new federal
      laws, local planning regulations, and increased public involvement. This article
      describes the use of an integer programming tool, Multiple Choice Knapsack
      Problem (MCKP), to provide optimal solutions to transportation programming
      problems in cases where alternative versions of projects are under consideration.
      In this paper, optimization methods for use in the transportation programming
      process are compared and then the process of building and solving the
      optimization problems is discussed. The concepts about the use of MCKP are
      presented and a real-world transportation programming example at various budget
      levels is provided. This article illustrates how the use of MCKP addresses the
      modern complexities and provides timely solutions in transportation programming
      practice. While the article uses transportation programming as a case study, MCKP
      can be useful in other fields where a similar decision among a subset of the
      alternatives is required.

PMID- 19596438
TI  - Sibling caretaking in immigrant families: understanding cultural practices to
      inform child welfare practice and evaluation.
AB  - The field of migration studies has well-documented children and youth's roles as
      'culture brokers,' by which they mediate relationships, information, and services
      between the immigrant household and the institutions of the host society. There
      is growing interest in understanding the contribution of children and youth to
      socially valued reproductive activity within immigrant households in the United
      States. Ethnographic studies reveal that children and adolescents in immigrant
      families have significant responsibilities related to daily life and family
      functioning. This article focuses on the practice of sibling caretaking, in which
      older children supervise and socialize younger children, according to culturally
      informed family roles, responsibilities, and obligations. The purpose of this
      review is twofold: (1) to familiarize practitioners and evaluators with this
      cross-cultural practice; and (2) to discuss the implications of sibling
      caretaking with regard to the identification of familial risk and protective
      factors associated with migration and acculturation, and factors that inform
      culturally sensitive assessments, interventions, and evaluations related to
      family functioning and social support.

PMID- 19596439
TI  - Molecular detection and quantification of the protozoan Bonamia ostreae in the
      flat oyster, Ostrea edulis.
AB  - Bonamia ostreae is an intracellular protozoan which is recognized as a cause of
      mortality in European populations of flat oysters (Ostrea edulis). Based on the
      recent characterization of actin genes of B. ostreae, specific primers were
      designed for real-time PCR using SYBR Green chemistry. Specificity was
      demonstrated by the unique melting temperature peak observed in positive samples
      and by the lack of amplification in samples of oysters infected by closely
      related parasites, including Bonamia exitiosa. A calibration curve using a cloned
      template was defined to estimate copy number. The assay had a 6 log- dynamic
      range, mean inter- and intra-assay variation coefficients of <1% and a minimum
      detection limit of 50 gene copies per reaction. Using infected oyster samples as
      templates, the assay was at least 10-fold more sensitive than conventional PCR.
      The quantitative assay was applied to test 132 oysters, and results were compared
      with the heart imprint method. There was a strong correlation between both
      techniques, and the results showed that the real-time PCR assay should be useful
      for studies of the ecology of B. ostreae and its host-parasite relationship.

PMID- 19596440
TI  - Subconjunctival hemorrhage and conjunctivochalasis.
AB  - OBJECTIVE: Subconjunctival hemorrhage (SCH) is a relatively common disease, but
      there have been no reports concerning the relationship between SCH and
      conjunctivochalasis (CCh). We compared the grade of CCh between patients with SCH
      and control patients. DESIGN: Prospective, nonrandomized study. PARTICIPANTS: A
      total of 104 patients with SCH aged 41 to 94 years and 120 age- and gender
      matched controls aged 41 to 94 years were enrolled. METHODS: The conjunctiva was
      divided into the following 8 equal areas: superior, superior/nasal, nasal,
      inferior/nasal, inferior, inferior/temporal, temporal, and superior/temporal. The
      age, gender, medical history, ocular history, site of hemorrhage, grade of CCh at
      3 locations (nasal, middle, and temporal), and other parameters of CCh were
      determined in all subjects. MAIN OUTCOME MEASURES: Grade of each CCh parameter
      and location of SCH. RESULTS: The mean grade of CCh was higher in patients with
      SCH than in control patients at the nasal (P<0.00001), middle (P<0.00001), and
      temporal areas (P<0.00001). The downward gaze- or digital pressure-dependent
      changes of CCh and the frequency of superficial punctate keratitis were all
      increased in SCH patients compared with control patients (P<0.00001, P<0.00001,
      and P = 0.00106, respectively). The number of areas involved by SCH and the
      presence of SCH in each area were positively correlated with the grade of each
      CCh-related parameter (P<0.05). CONCLUSIONS: This was the first assessment of the
      grade of CCh in a large series of consecutive patients with SCH. Our results
      strongly suggest that CCh may have an important role in the pathogenesis of SCH.

PMID- 19596442
TI  - New FTIR methodology for the evaluation of (13)C/(12)C isotope ratio in
      Helicobacter pylori infection diagnosis.
AB  - OBJECTIVES: The objective of this work was to assess the reliability of a newly
      developed FTIR (Fourier Transform Infrared spectroscopy) technique for (13)C-urea
      breath test in the non-invasive diagnosis of Helicobacter pylori infection, in
      comparison to those currently used, isotope ratio mass spectrometry (IRMS) and
      non-dispersive isotope-selective infrared spectrometry (NDIRS). This new
      methodology is based on the use of a very less expensive and sophisticated FTIR
      than IRMS and NDIRS. MATERIALS AND METHODS: Sixty patients (male and female, aged
      between 15-70 years) with dyspeptic symptoms, like the epigastric pain, were
      tested for H. pylori infection using (13)C-urea breath test. Triplicate breath
      samples were collected before and 30 min after drinking the test solution (75 mg
      (13)C-urea dissolved in 200 ml 0.1M citric acid). Analysis of delta(13)C were
      conducted in parallel by means of IRMS, NDIRS and FTIR in order to compare the
      results. RESULTS: Delta-over-baseline values were over 5 per thousand in 18
      patients, ranging from 8.81 to 60.88 per thousand for IRMS measurements, from 7.2
      to 61.2 per thousand for NDIRS and from 7.7 to 61.2 per thousand for FTIR
      measurements. The remaining 42 subjects had values well below the 5 per thousand
      cut-off. The results of the baseline-corrected (13)CO(2) exhalation values
      between FTIR and IRMS/NDIRS were in good agreement. CONCLUSIONS: The newly
      developed FTIR methodology has been demonstrated to be a reliable and accurate
      analytical tool, low cost and easy-to-operate, which permits a highly specific
      measurement of (13)C enrichment in breath samples. As IRMS and NDIRS it allows to
      adequately discriminate between infected and non-infected subjects.

PMID- 19596441
TI  - Misfolded maltose binding protein MalE219 induces the CpxRA envelope stress
      response by stimulating phosphoryl transfer from CpxA to CpxR.
AB  - In Escherichia coli, the CpxRA sensor regulator system is induced by a variety of
      signals, including pH, osmolarity, metals and misfolded envelope proteins. Here,
      we analyzed the effect of the folding defective maltose binding protein MalE219
      on the reconstituted Cpx signalling pathway in detail. Surprisingly, autokinase
      and phosphatase activities of the reconstituted CpxA-6His protein remained
      unaffected, whereas phosphotransfer to CpxR became activated by MalE219. Since
      stimulation occurred only in CpxA-containing proteoliposomes, our data provide
      the first biochemical indication of allosteric stimulation due to direct contact
      between MalE219 and the sensor kinase CpxA. Consequently, we suggest that this
      direct interaction is a new mechanism enabling the Cpx pathway to sense misfolded
      proteins.

PMID- 19596443
TI  - The effect of amino acid substitution in the imperfect repeat sequences of alpha
      synuclein on fibrillation.
AB  - Human alpha-synuclein is the causative protein of several neurodegenerative
      diseases, such as Parkinson's disease (PD) and dementia with Lewy Bodies (DLB).
      The N-terminal half of alpha-synuclein contains seven imperfect repeat sequences.
      One of the PD/DLB-causing point mutations, E46K, has been reported in the
      imperfect repeat sequences of alpha-synuclein, and is prone to form amyloid
      fibrils. The presence of seven imperfect repeats in alpha-synuclein raises the
      question of whether or not mutations corresponding to E46K in the other imperfect
      KTKE(Q)GV repeats have similar effects on aggregation and fibrillation, as well
      as their propensities to form alpha-helices. To investigate the effect of E(Q)/K
      mutations in each imperfect repeat sequence, we substituted the amino acid
      corresponding to E46K in each of the seven repeated sequences with a Lys residue.
      The mutations in the imperfect KTKE(Q)GV repeat sequences of the N-terminal
      region were prone to decrease the lag time of fibril formation. In addition, AFM
      imaging suggested that the Q24K mutant formed twisted fibrils, while the other
      mutants formed spherical aggregates and short fibrils. These observations
      indicate that the effect of the mutations on the kinetics of fibril formation and
      morphology of fibrils varies according to their location.

PMID- 19596444
TI  - Genetic causes of mitochondrial DNA depletion in humans.
AB  - Mitochondrial DNA (mtDNA) depletion is characterized by a profound reduction of
      mtDNA copy number. The maintenance of mtDNA copy number requires several nuclear
      encoded factors involved in replication and in dNTP supply. In the past decade
      mutations in several of these factors have been reported in a growing number of
      syndromes. This article reviews the current knowledge of genes causing
      mitochondrial DNA depletion syndromes.

PMID- 19596445
TI  - Expression and localization of voltage dependent potassium channel Kv4.2 in
      epilepsy associated focal lesions.
AB  - An increasing number of observations suggest an important role for voltage-gated
      potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of
      Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using
      immunocytochemistry in different epilepsy-associated focal lesions. In
      hippocampal sclerosis (HS), Kv4.2 and pKv4.2 immunoreactivity (IR) was reduced in
      the neuropil in regions with prominent neuronal cell loss. In both HS and
      malformations of cortical development (MCD), intense labeling was found in
      neuronal somata, but not in dendrites. Strong NCS-1 IR was observed in neurons in
      all lesion types. Western blot analysis demonstrated an increase of total Kv4.2
      in all lesions and activation of the ERK pathway in HS and ganglioglioma. These
      findings indicate that Kv4.2 is expressed in both neuronal and glial cells and
      its regulation may involve potassium channel interacting proteins, alterations in
      the subcellular localization of the channel, as well as phosphorylation-mediated
      posttranslational modifications.

PMID- 19596446
TI  - Outcome results of a psycho-educational intervention in pregnancy to prevent PPD:
      a randomized control trial.
AB  - BACKGROUND: This study aims to evaluate the effectiveness of an antenatal psycho
      educational intervention to prevent postpartum depression in Mexican women.
      METHOD: Pregnant women at high risk for depression were randomized to
      intervention or a usual care condition. Assessments of depression (SCID, BDI-II)
      occurred during pregnancy, 6 weeks and 4-6 months postnatally, and subjective
      impact of the intervention in the postpartum. RESULTS: Of the 6484 women
      approached, 377 were eligible and consented to randomization (250 intervention,
      127 control). Sixty-eight intervention (27.2%) and 68 (53.5%) control
      participants completed the three assessment periods. The cumulative incidence of
      major depression over three time periods was significantly lower (p<0.05) in the
      intervention (10.7%) than the control group (25%). Repeated-measures analysis of
      variance showed a significant reduction of BDI-II in both groups, but no
      significant treatment effect. Even when controlling for initial levels of
      depressive and anxiety symptoms, a treatment effect on depressive symptoms could
      not be confirmed, although there was a trend demonstrating that intervention
      participants with high initial symptoms had a larger reduction of BDI-II. Most
      participants that completed the intervention reported that it had a medium to
      great influence on their well-being, depression, current problems, role as
      mothers and their relationship with the baby. LIMITATIONS: Attrition was the most
      salient methodological problem in this study. CONCLUSIONS: This is the first
      randomized control depression prevention trial in high-risk pregnant Mexican
      women. Available data are consistent with the possibility that the incidence of
      depression may have been reduced by the intervention, but differential attrition
      makes interpretation of the findings difficult.

PMID- 19596447
TI  - Bipolar disorder as a risk factor for repeat DUI behavior.
AB  - BACKGROUND: Bipolar disorder (BD) is more prevalent among people with substance
      use disorders (SUD) than the general population. SUD among recidivist driving
      under the influence (DUI) populations are extremely prevalent; not surprisingly,
      recent evidence suggests that rates of BD also are elevated among DUI offenders.
      Studies of BD patients with SUD have found high prevalence of other psychiatric
      disorders and relatively low rate of treatment engagement. This study examines
      both the prevalence of other mental disorders and treatment status among a cohort
      of DUI offenders with BD and SUD. METHODS: A consecutively selected cohort
      (N=729) of repeat DUI offenders attending a two-week inpatient treatment program
      completed a standardized diagnostic interview (the Composite International
      Diagnostic Interview: CIDI). The CIDI generated DSM-IV diagnoses. RESULTS: This
      study yielded three main results for this repeat DUI offender sample: (1) BD is
      associated with significantly higher lifetime prevalence of alcohol, drug, and
      non-substance psychiatric disorders (e.g., PTSD); (2) approximately one quarter
      of BD participants have not discussed their mania with a professional; and (3)
      only half of the BD participants in this cohort have had mania treatment they
      consider effective and even fewer have had any treatment during the past twelve
      months. LIMITATIONS: Participants were predominantly Caucasian males attending
      treatment as a sentencing option in a single Massachusetts DUI program.
      CONCLUSION: These findings suggest that clinicians in DUI treatment settings
      should consider both evaluating for BD and initiating therapy.

PMID- 19596448
TI  - Integration of genetic and genomic methods for identification of genes and gene
      variants encoding QTLs in the nonhuman primate.
AB  - We have developed an integrated approach, using genetic and genomic methods, in
      conjunction with resources from the Southwest National Primate Research Center
      (SNPRC) baboon colony, for the identification of genes and their functional
      variants that encode quantitative trait loci (QTL). In addition, we use
      comparative genomic methods to overcome the paucity of baboon specific reagents
      and to augment translation of our findings in a nonhuman primate (NHP) to the
      human population. We are using the baboon as a model to study the genetics of
      cardiovascular disease (CVD). A key step for understanding gene-environment
      interactions in cardiovascular disease is the identification of genes and gene
      variants that influence CVD phenotypes. We have developed a sequential
      methodology that takes advantage of the SNPRC pedigreed baboon colony, the
      annotated human genome, and current genomic and bioinformatic tools. The process
      of functional polymorphism identification for genes encoding QTLs involves
      comparison of expression profiles for genes and predicted genes in the genomic
      region of the QTL for individuals discordant for the phenotypic trait mapping to
      the QTL. After comparison, genes of interest are prioritized, and functional
      polymorphisms are identified in candidate genes by genotyping and quantitative
      trait nucleotide analysis. This approach reduces the time and labor necessary to
      prioritize and identify genes and their polymorphisms influencing variation in a
      quantitative trait compared with traditional positional cloning methods.

PMID- 19596449
TI  - Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes.
AB  - Understanding the immunopathogenesis of neuroimmunological diseases of the CNS
      requires a robust method for isolating and characterizing the immune effector
      cells that infiltrate the spinal cord in animal models. We have developed a
      simple and rapid isolation method that produces high yields of spinal cord
      infiltrating leukocytes from a single demyelinated spinal cord and which
      maintains high surface expression of key immunophenotyping antigens. Using this
      method and the Theiler's virus model of chronic demyelination, we report the
      presence of spinal cord infiltrating acute effector CD8(+) lymphocytes that are
      CD45(hi)CD44(lo)CD62L(-) and a population of spinal cord infiltrating target
      effector memory CD8(+) lymphocytes that are CD45(hi)CD44(hi)CD62L(-). These cells
      respond robustly to ex vivo stimulation by producing interferon gamma but do not
      exhibit specificity for Theiler's virus in a cytotoxicity assay. We conclude that
      target-derived lymphocytes in a mouse model of chronic spinal cord demyelination
      may have unique functional specificities.

PMID- 19596450
TI  - Factors associated with acute otitis media in children due to penicillin
      intermediately resistant Streptococcus pneumoniae.
AB  - OBJECTIVES: This study was conducted to analyze the association between recent
      antimicrobial use and acute otitis media (AOM) due to Streptococcus pneumoniae
      intermediately resistant to penicillin (PISP). The influence of drug resistance
      on the clinical course of AOM was also assessed. METHODS: A retrospective cohort
      study was conducted in infants at Japanese Red Cross Medical Center, Tokyo.
      Children included in the study were under 24 months of age and diagnosed with AOM
      due to infection with S. pneumoniae between April 2002 and March 2007. Crude risk
      ratios (cRR) of PISP infection in cases with recent antibiotic use and other
      factors were obtained. The Mantel-Haenszel estimate was applied for the
      adjustment of cRR. RESULTS: Of 35 children, 13 had AOM due to penicillin
      susceptible S. pneumoniae (PSSP) and 22 had AOM due to PISP. The adjusted risk
      ratio (aRR) of penicillin antibiotic use within 1 month was 1.99 (95% confidence
      interval (CI): 1.36-2.92), and the aRR of penicillin antibiotic use within 1 week
      was 1.93 (95% CI: 1.33-2.67). Recent use of penicillin antibiotics was an
      associated factor for AOM due to PISP. The clinical course was not clearly
      different between cases infected with PSSP and those with PISP. CONCLUSION:
      Recent use of penicillin antibiotics might be a selective pressure for PISP.

PMID- 19596451
TI  - Momentary reductions of attention permit greater processing of irrelevant
      stimuli.
AB  - Momentary reductions of attention can have extremely adverse outcomes, but it
      remains unclear whether increased distraction from irrelevant stimuli contributes
      to such outcomes. To investigate this hypothesis, we examined trial-by-trial
      relationships between brain activity and response time in twenty healthy adults
      while they performed a cross-modal selective attention task. In each trial,
      participants identified a relevant visual letter while ignoring an irrelevant
      auditory letter, which was mapped either to the same response as the visual
      letter (congruent trials) or to a different response (incongruent trials). As
      predicted, reductions of attention (i.e., increases of response time) were
      associated not only with decreased activity in sensory regions that processed the
      relevant visual stimuli, suggesting a failure to enhance the processing of those
      stimuli, but also with increased activity in sensory regions that processed the
      irrelevant auditory stimuli, suggesting a failure to suppress the processing of
      those stimuli. Reductions of attention were also linked to larger increases of
      activity in incongruent than in congruent trials in anterior cingulate regions
      that detect response conflict, suggesting that failing to suppress the sensory
      processing of the irrelevant auditory stimuli during attentional reductions
      allowed those stimuli to more readily activate conflicting responses in
      incongruent trials. These findings indicate that heightened levels of distraction
      during momentary reductions of attention likely stem, at least in part, from
      increased processing of irrelevant stimuli.

PMID- 19596453
TI  - Molecular phylogenetics of the hummingbird genus Coeligena.
AB  - Advances in the understanding of biological radiations along tropical mountains
      depend on the knowledge of phylogenetic relationships among species. Here we
      present a species-level molecular phylogeny based on a multilocus dataset for the
      Andean hummingbird genus Coeligena. We compare this phylogeny to previous
      hypotheses of evolutionary relationships and use it as a framework to understand
      patterns in the evolution of sexual dichromatism and in the biogeography of
      speciation within the Andes. Previous phylogenetic hypotheses based mostly on
      similarities in coloration conflicted with our molecular phylogeny, emphasizing
      the unreliability of color characters for phylogenetic inference. Two major
      clades, one monochromatic and the other dichromatic, were found in Coeligena.
      Closely related species were either allopatric or parapatric on opposite mountain
      slopes. No sister lineages replaced each other along an elevational gradient. Our
      results indicate the importance of geographic isolation for speciation in this
      group and the potential interaction between isolation and sexual selection to
      promote diversification.

PMID- 19596452
TI  - Phylogeographic history of the New Zealand stick insect Niveaphasma annulata
      (Phasmatodea) estimated from mitochondrial and nuclear loci.
AB  - We have assessed the utility of a single-copy nuclear locus and mitochondrial DNA
      (mtDNA) in a phylogeographic study of the New Zealand stick insect Niveaphasma
      annulata (Hutton). We amplified sequences from the mitochondrial cytochrome
      oxidase subunit I (COI) gene and the single-copy nuclear gene elongation factor
      1alpha (EF1alpha) from 97 individuals. Allelic phase at the EF1alpha locus was
      determined using Denaturing Gradient Gel Electrophoresis. Phylogenetic analyses
      showed broad congruence between the geographic distribution of three major COI
      clades and EF1alpha alleles, which suggested that the phylogenetic patterns
      reflect population history rather than lineage sorting. However, the geographic
      boundaries of these clades were not always in exact agreement between the two
      loci. Our data indicate that Niveaphasma annulata was most likely separated into
      a number of refugia during Pleistocene glacial advances. Subsequent to glacial
      retreat these refugial populations have expanded and now form a number of zones
      of secondary contact. We contrast these patterns with those observed from other
      New Zealand taxa. Our study offers compelling evidence for the use of nuclear
      genes alongside mtDNA for future phylogeographic studies.

PMID- 19596454
TI  - Phylogeography of the frog Leptodactylus validus (Amphibia: Anura): patterns and
      timing of colonization events in the Lesser Antilles.
AB  - The frog Leptodactylus validus occurs in northern South America, Trinidad and
      Tobago, and the southern Lesser Antilles (Grenada and St. Vincent). Mitochondrial
      DNA sequences were used to perform a nested clade phylogeographic analysis
      (NCPA), to date colonization events, and to analyze colonization patterns using
      on a relaxed molecular clock and coalescent simulations. L. validus originated on
      the mainland and first colonized Trinidad with subsequent independent
      colonizations of Tobago and the Lesser Antilles from Trinidad. The NCPA suggests
      a historical vicariant event between populations in Trinidad and Tobago from
      those in the Lesser Antilles. The colonization of Trinidad occurred approximately
      1 million years ago (mya) and the colonization of the Lesser Antillean islands
      occurred approximately 0.4 mya. The coalescent approach supported the scenario
      where L. validus dispersed from Trinidad to St. Vincent and from there to
      Grenada, a dispersal event that could have been mediated by human introduction as
      recent as 1600 years ago.

PMID- 19596455
TI  - Phylogenetic analyses of the leaf beetle genus Galerucella: evidence for host
      switching at speciation?
AB  - It is still the subject of lively debate whether sympatric speciation is a
      general mode of speciation as opposed to allopatric speciation. In herbivorous
      insects, host switching, i.e. colonization of, and adaptation to, a new host by a
      herbivore, has been proposed as one of the driving mechanisms of sympatric
      speciation. Evidence for host switching as a speciation driving mechanism can be
      inferred from phylogenies of herbivores and host plants: if the host plant
      phylogeny is randomly distributed over the herbivore phylogeny, this indicates
      host switching. The Chrysomelid beetle genus Galerucella is a good taxon to study
      for evidence of host switching, because several closely related Galerucella
      species form sympatric species complexes associated with various unrelated plant
      species. Here we present the phylogenetic relationships of 10 species in the
      genus Galerucella, based on the mitochondrial gene fragments of the NADH-2 (410
      bp) and CO-I (659 bp) genes, and analyzed with Bayesian, Maximum Likelihood and
      Maximum Parsimony methods. The resulting molecular phylogenetic tree proved to be
      largely congruent with morphologically based taxonomy. The host-associated taxa
      of the Galerucellanymphaeae species complex are not defined as distinct gene
      pools under the phylogenetic species concept (PSC), however, the species complex
      as a whole is. Two results indicate the contribution of host switching to the
      speciation of Galerucella: (1) the host-associated taxa of the G. nymphaeae
      species complex have diverged very recently and (2) constrained ML analyses
      showed that host use constraints led to a significantly different Galerucella
      tree compared to unconstrained analyses. This evidence for host switching,
      together with the observation that several sister taxa using unrelated host
      plants live in sympatry, suggests that sympatric speciation by host race
      formation can be an important mode of speciation in this genus.

PMID- 19596456
TI  - Melanomas display increased cytoprotection to hypericin-mediated cytotoxicity
      through the induction of autophagy.
AB  - Photodynamic therapy (PDT) as a regime for melanoma is of limited success due to
      factors such as the efficacy of the photosensitizer used, penetration depth and
      the presence of pigment. We characterised a pigmented and an unpigmented melanoma
      cell line with respect to their phenotypes. Cell viability was assessed after
      exposure to hypericin, a UVA-activated photosensitizer. Exposure to 3 microM
      activated hypericin induced a cytoprotective (autophagic) response from both cell
      lines. However, the pigmented cells accumulated a large amount of glycogen in
      their cytoplasm. We hypothesise that the treatment induces an initial
      cytoprotective response through autophagy, but with increased stress results in a
      different mode of cell death in pigmented melanoma cells from unpigmented cells.
      These results indicate that hypericin-PDT could be an adjuvant therapy for
      melanoma.

PMID- 19596457
TI  - The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors
      in brain structures of low and high anxiety rats subjected to extinction trials
      and re-learning of a conditioned fear response.
AB  - We designed an animal model to examine the mechanisms of differences in
      individual responses to aversive stimuli. We used the rat freezing response in
      the context fear test as a discriminating variable: low responders (LR) were
      defined as rats with a duration of freezing response one standard error or more
      below the mean value, and high responders (HR) were defined as rats with a
      duration of freezing response one standard error or more above the mean value. We
      sought to determine the colocalisation of c-Fos and glucocorticoid receptors
      immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear
      training, two extinction sessions and re-learning of a conditioned fear. We found
      that HR animals showed a marked decrease in conditioned fear in the course of two
      extinction sessions (16 days) in comparison with the control and LR groups. The
      LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos)
      and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and
      medial orbital cortex after re-learning a contextual fear. HR rats showed
      increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the
      basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in
      comparison with LR animals. Our data indicate that recovery of a context-related
      behaviour upon re-learning of contextual fear is accompanied in HR animals by a
      selective increase in c-Fos expression and GRs-ir in the DG area of the
      hippocampus.

PMID- 19596458
TI  - Obstacle-negotiating gait and related physical measurement indicators for the
      community-dwelling elderly in Japan.
AB  - The aim of this study is to assess obstacle-negotiating gait (ONG) and explore
      its related physical factors. Subjects comprised 571 community-dwelling persons
      (195 men and 376 women) age>or=65 years and without cognitive impairment. ONG,
      timed up and go (TUG), and stair-climbing were measured and their relations were
      assessed. Walking ability (usual walking speed=UWS and daily walking steps=DWS),
      balance deficiency, and musculoskeletal function (handgrip strength and bone
      health) were examined objectively to explore ONG related physical factors.
      Logistic regression and general linear model analysis were performed with
      adjustment for age and body mass index (BMI). Time of ONG was 7.72s in men and
      8.93s in women. Logistic regression analysis showed that the fast tertiles of ONG
      corresponding to the fast levels of TUG and stair-climbing had the highest odds
      ratio values. General linear model analysis showed that ONG was significantly
      associated with UWS and balance deficiency (no) in men, and with UWS, handgrip
      strength, DWS and balance deficiency (no) in women. Overall, ONG was considerably
      associated with falls screening tools and its determinants were also the main
      causes of falls. Training in ONG could be an attractive strategy for the
      prevention of falls among the elderly.

PMID- 19596459
TI  - Physical and social functional abilities seem to be maintained by a multifaceted
      randomized controlled nutritional intervention among old (>65 years) Danish
      nursing home residents.
AB  - The purpose was to test the hypothesis that a multifaceted 11 weeks randomized
      controlled intervention would have a significant influence of functional
      abilities in old nursing home residents. Participants were 121 old (>65 years)
      residents in seven Danish nursing homes. The intervention consisted of nutrition
      (chocolate, homemade oral supplements), group exercise (moderate intensity) and
      oral care. Measurements taken were weight, body mass index (BMI), energy and
      protein intake, and functional abilities (activities of daily living=ADL,
      cognitive performance, and social engagement). The results showed that the
      nutrition and exercise were well accepted. After 11 weeks the change in % weight
      (1.3 vs. -0.6%, p=0.005), % BMI (0.4 vs. -0.2%, p=0.003), energy intake (0.7 vs. 
      0.3 MJ/day, p=0.084) and protein intake (5 vs. -2g/day, p=0.012) was higher in
      the intervention group than in the control group. Also, after 11 weeks, social
      and physical function had decreased in the control group but was unchanged in the
      intervention group. The difference between groups was significant in relation to
      social engagement (p=0.009). After the end of the intervention both groups had
      lost weight and physical function. Cognitive performance did not change, at any
      time. In conclusion, it seems possible to maintain social (and physical)
      functional abilities in old nursing home residents by means of a multifaceted
      intervention.

PMID- 19596460
TI  - Centrioles in flies: the exception to the rule?
AB  - Centrioles and basal bodies are MT based structures that present a highly
      conserved ninefold symmetry. Centrioles can be found at the core of the
      centrosome where they participate in PCM recruitment and organization,
      contributing to cytoplasmic MT nucleation. Basal bodies are normally located
      closely to the plasma membrane where they are responsible for axoneme assembly to
      form structures such as cilia or flagella. While it is well accepted that these
      organelles have important roles in cell and tissue organization, their
      contribution to certain phases of animal development is still not entirely
      established. Here we review the role of centrosomes and cilia in Drosophila
      melanogaster and briefly discuss the implications of these findings to other
      model organisms.

PMID- 19596461
TI  - Digital pathology in drug discovery and development: multisite integration.
AB  - Digital pathology is an emerging technology that provides an image-based
      environment for managing and interpreting the information generated from a
      digitized glass slide, offering substantial improvements in pharmaceutical drug
      development across discovery, preclinical GLP pathology and oncology clinical
      trials. Digital pathology is transforming global pharmaceutical research by
      enabling data sharing to integrate dispersed pharma pathology labs around the
      world. This article reviews the stages of multisite digital pathology integration
      in large pharmaceutical companies, offering suggestions for success and
      highlighting challenges.

PMID- 19596462
TI  - Herbals in the control of ageing.
AB  - The significance of herbals and herbal products is gaining worldwide recognition.
      The concept of complementary or alternative medicine is becoming much more widely
      accepted, and there is an increasing belief in the efficacy of herbal remedies.
      Recently, the role of herbal drugs, herbal products and certain phytochemicals in
      the control of ageing has been documented using modern scientific approaches.
      This review pulls together such studies and critiques the efficacy and value of
      herbal medicines in the control of the ageing process.

PMID- 19596463
TI  - Rectal cancer multidisciplinary management: evidences and future landscape.

PMID- 19596464
TI  - Breathing mechanics during exercise with added dead space reflect mechanisms of
      ventilatory control.
AB  - Small increases in external dead space (V(D)) augment the exercise ventilatory
      response via a neural mechanism known as short-term modulation (STM). We
      hypothesized that breathing mechanics would differ during exercise, increased
      V(D) and STM. Men were studied at rest and during cycle exercise (10-50W) without
      (Control) and with added V(D) (200-600ml). With added V(D), V(T) increased via
      increased end-inspiratory lung volume (EILV), with no change in end-expiratory
      lung volume (EELV), indicating recruitment of inspiratory muscles only. With
      exercise, V(T) increased via both decreased EELV and increased EILV, indicating
      recruitment of both expiratory and inspiratory muscles. A significant interaction
      between the effects of exercise and V(D) on mean inspiratory flow indicated that
      the augmented exercise ventilatory response with added V(D) (i.e. STM) resulted
      from increased drive to the inspiratory muscles. These results reveal different
      patterns of respiratory muscle recruitment among experimental conditions. Hence,
      we conclude that fundamental differences exist in the neural control of
      ventilatory responses during exercise, increased V(D) and STM.

PMID- 19596465
TI  - Presynaptic regulation of isolated neonatal rat carotid body type I cells by
      histamine.
AB  - The type I cells are the chemoreceptive elements of the carotid bodies and are
      critical in defining the ventilatory response to hypoxia and hypercapnia. Recent
      evidence has suggested that histamine is released by the carotid body in response
      to hypoxia and acts as an excitatory neurotransmitter. Here we use isolated
      neonatal rat type I cells to assess the presynaptic actions of histamine and
      define the receptor subtypes that mediate them. All four histamine receptor
      subtypes are expressed on the type I cells, however activation of these receptors
      with histamine or selective agonists caused no rise in intracellular calcium
      ([Ca(2+)](i)) and histamine did not augment calcium entry or modulate macroscopic
      currents evoked in type I cells. Thus activation of histamine receptors on type I
      cells is unlikely to provide a presynaptic positive feedback mechanism during
      chemotransduction and any excitatory role attributed to the actions of histamine
      is likely to come from a postsynaptic effect on the carotid sinus nerve (CSN).

PMID- 19596466
TI  - Metabolic cost and mechanical work for the step-to-step transition in walking
      after successful total ankle arthroplasty.
AB  - The aim of this study was to investigate whether impaired ankle function after
      total ankle arthroplasty (TAA) affects the mechanical work during the step-to
      step transition and the metabolic cost of walking. Respiratory and force plate
      data were recorded in 11 patients and 11 healthy controls while they walked
      barefoot at a fixed walking speed (FWS, 1.25 m/s) and at their self-selected
      speed (SWS). At FWS metabolic cost of transport was 28% higher for the TAA group,
      but at SWS there was no significant increase. During the step-to-step transition,
      positive mechanical work generated by the trailing TAA leg was lower and negative
      mechanical work in the leading intact leg was larger. Despite the increase in
      mechanical work dissipation during double support, no significant differences in
      total mechanical work were found over a complete stride. This might be a result
      of methodological limitations of calculating mechanical work. Nevertheless,
      mechanical work dissipated during the step-to-step transition at FWS correlated
      significantly with metabolic cost of transport: r=.540. It was concluded that
      patients after successful TAA still experienced an impaired lower leg function,
      which contributed to an increase in mechanical energy dissipation during the step
      to-step transition, and to an increase in the metabolic demand of walking.

PMID- 19596468
TI  - Interview with Dr. Heinz-Hubert Fischer, recruitment consultant with Kelly
      Scientific Resources. Interview by Valentina Ahl.

PMID- 19596470
TI  - Transcription factor AP-2beta inhibits glucose-induced insulin secretion in
      cultured insulin-secreting cell-line.
AB  - AIM: We previously identified the transcription factor activating enhancer
      binding protein-2beta (AP-2beta) gene as a new candidate for conferring
      susceptibility to type 2 diabetes. To ascertain the possible involvement of AP
      2beta in the pathogenesis of type 2 diabetes we examined the effects of AP-2beta
      on glucose-induced insulin secretion. METHODS: We measured the insulin secretion
      stimulated by glucose, tolbutamide, or KCl in the HIT-T15 cells infected with
      adenovirus vectors encoding AP-2beta or LacZ (control). RESULTS: We identified
      clear expression of AP-2beta in isolated rat pancreatic islets and in HIT-T15
      cells. Glucose-induced increase in insulin secretion was significantly inhibited
      in AP-2beta-overexpressing cells (LacZ, 5.0+/-0.8 ng h(-1)mg(-1) protein; AP
      2beta, 1.7+/-0.2 ng h(-1)mg(-1) protein; P=0.0015), whereas insulin expression
      was the same in both types of cells. Tolbutamide-induced insulin secretion was
      also suppressed in the AP-2beta-overexpressing cells, but KCl-induced insulin
      secretion was not affected by AP-2beta overexpression. In addition, Kir6.2 and
      glucokinase expression was significantly decreased in the AP-2beta-overexpressing
      cells. CONCLUSION: We identified for the first time that AP-2beta expressed and
      functioned in insulin-secreting cell-line HIT-T15. These results suggest that AP
      2beta contributes to susceptibility to type 2 diabetes by inhibiting glucose
      induced insulin secretion in pancreatic beta cells.

PMID- 19596469
TI  - Evidence that even "normal" albuminuria may denote incipient GFR reduction in
      patients with type 2 diabetes mellitus.
AB  - AIMS: In patients with diabetes and microalbuminuria, small changes of GFR could
      have been missed, due to the lack of sensitive methodology for GFR determination
      in clinical practice (creatinine based calculations). Therefore we explored the
      relation of the degree of albumin excretion with Cystatin C, which has been
      recently proved to be a better marker of GFR, compared to serum creatinine.
      METHODS: We studied 179 patients with type 2 diabetes, in whom renal function and
      microalbuminuria were evaluated. RESULTS: In patients with normal renal function,
      GFR/MDRD>or=60 ml/min/1.73 m(2), (n=79), urinary albumin concentration (UAC) was
      significantly correlated with Cystatin C, both in patients with normoalbuminuria
      (r=0.547, p<0.023) or microalbuminuria (r=0.305, p<0.035), while it was not
      correlated either with serum creatinine or calculated creatinine clearance. In
      patients with GFR/MDRD<60 ml/min/1.73 m(2), (n=100), UAC was significantly
      correlated with Cystatin C, also both in patients with normoalbuminuria (r=0.536,
      p<0.032) or microalbuminuria (r=0.340, p<0.016), while it was significantly
      correlated with serum creatinine and calculated creatinine clearance only in
      those with microalbuminuria. CONCLUSIONS: Subtle changes in renal function, as
      judged by Cystatin C concentration, may parallel the degree of albuminuria, even
      in the normoalbuminuric stage. This finding needs further confirmation by more
      appropriate methodology in prospective follow up studies.

PMID- 19596467
TI  - MLPA analysis in 30 Sotos syndrome patients revealed one total NSD1 deletion and
      two partial deletions not previously reported.
AB  - Sotos syndrome (MIM #117550) is an autosomal dominant condition characterized by
      pre and postnatal overgrowth, macrocephaly and typical facial gestalt with
      frontal bossing, hypertelorism, antimongoloid slant of the palpebral fissures,
      prominent jaw and high and narrow palate. This syndrome is also frequently
      associated with brain, cardiovascular, and urinary anomalies and is occasionally
      accompanied by malignant lesions such as Wilms tumour and hepatocarcinoma. The
      syndrome is known to be caused by mutations or deletions of the NSD1 gene. To
      detect both 5q35 microdeletions and partial NSD1 gene deletions we screened 30
      Brazilian patients with clinical diagnosis of Sotos syndrome by multiplex
      ligation dependent probe amplification. We identified one patient with a total
      deletion of NSD1 and neighbouring FGFR4, other with missing NSD1 exons 13-14 and
      another with a deletion involving FGFR4 and spanning up to NSD1 exon 17. All
      deletions were de novo. The two NSD1 partial deletions have not been previously
      reported. The clinical features of the three patients included a typical facial
      gestalt with frontal bossing, prominent jaw and high anterior hairline;
      macrocephaly, dolichocephaly, large hands; neonatal hypotonia and jaundice. All
      presented normal growth at birth but postnatal overgrowth. Two patients with NSD1
      and FGFR4 gene deletions presented congenital heart anomalies.

PMID- 19596471
TI  - A single nucleotide polymorphism (SNP) rs2072907 in the adiponutrin gene (ADPN)
      was not associated with obesity and type 2 diabetes in Chinese population.
AB  - We aimed to assess the association between adiponutrin gene (ADPN) SNPrs2072907
      and obesity or type 2 diabetes mellitus (T2DM) in Chinese population. 500 T2DM
      and 331 nondiabetic subjects were recruited. No association was found between
      SNPrs2072907 and obesity or T2DM. ADPN was not an obesity/T2DM susceptibility
      gene in Chinese population.

PMID- 19596472
TI  - Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty
      liver disease.
AB  - BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is a hepatic
      manifestation of metabolic syndrome that is closely associated with multiple
      factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and
      hypertension, making it difficult to treat NAFLD effectively using any
      monotherapy available to date. In this study, we propose a novel combination
      therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor,
      and acarbose (AC), an alpha-glucosidase inhibitor. METHODS: C57BL/6J mice were
      divided into five treatment groups as follows: basal diet (BD), high-fat diet
      (HFD) only, HFD with EZ (5mg/kg/day), HFD with AC (100mg/kg/day), and HFD with
      both EZ and AC for 24 weeks. RESULTS: Long-term combination therapy with EZ and
      AC significantly reduced steatosis, inflammation and fibrosis in the liver,
      compared with long-term monotherapy with either drug, in an HFD-induced NAFLD
      mouse model; the combination therapy also significantly increased the expression
      of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators
      activated receptor-alpha1 (PPAR-alpha1) in the liver, compared with either
      monotherapy, which may have led to the improvement in lipid metabolic disorder
      seen in this model. CONCLUSIONS: Combination therapy with EZ and AC for 24 weeks
      improved the histopathological findings in a mouse model of NAFLD.

PMID- 19596474
TI  - Fine characterization of intrahepatic NK cells expressing natural killer
      receptors in chronic hepatitis B and C.
AB  - BACKGROUND/AIMS: The fate of intrahepatic NK cell subsets in the course of HCV
      and HBV infections is not clearly understood. METHODS: Blood and intrahepatic
      CD56(+) NK cell subsets (expressing NKG2A, CD158a,h or CD158b,j receptors) from
      HCV or HBV patients were quantified by flow cytometry and localized by
      immunohistochemistry in liver biopsies. RESULTS: A significant reduction in NK
      cell frequency and a quantitative imbalance between CD56(bright) and CD56(dim)
      subsets were observed in chronic HCV patients as compared to HBV patients,
      underlining that the inflammatory environment is not the only cause of these
      phenomena. The proportions of intrahepatic NK cells expressing either NKG2A,
      and/or CD158a,h, CD158b,j differed significantly between HCV and HBV patients. A
      higher frequency of perforin among intrahepatic CD56(+)CD3(-) cells was observed
      in HCV compared to HBV patients. Double immunohistochemical staining showed that
      CD56(+)CD3(-) cells were localized within necrotic areas. Immune monitoring of
      circulating CD56 subsets revealed that CD3(-)CD56(bright)NKG2A(+) and CD3(
      )CD56(dim)NKG2A(+) cells were positively correlated with the necroinflammatory
      score and inversely correlated with viral load, respectively, in HCV patients.
      CONCLUSIONS: HCV and HBV affect NK cell subsets according to the status of the
      diseases, especially CD3(-)CD56(dim)NKG2A(+) and CD3(-)CD56(bright)NKG2A(+)
      cells, may be of interest for disease monitoring.

PMID- 19596475
TI  - Cigarette smoke exposure: a novel cofactor of NAFLD progression?

PMID- 19596473
TI  - Hepatocyte GP73 expression in Wilson disease.
AB  - BACKGROUND/AIMS: Wilson disease (WD) is a disorder of copper transport caused by
      mutations within the ATP7B gene. WD is phenotypically variable and can present
      with predominantly hepatic or neurologic manifestations. The mechanisms
      responsible for this variability are unknown. GP73, a Golgi membrane protein, is
      expressed in hepatocytes in response to acute and chronic liver disease. METHODS:
      Hepatocyte GP73 expression was examined in the livers of WD patients by
      semiquantitative immunohistochemistry. GP73 mRNA levels were measured in mice
      with a deletion of the WD gene (Atp7b(-/-)) by real-time PCR, and these values
      were compared to the concomitant histological abnormalities and previously
      reported copper levels. RESULTS: Hepatocyte GP73 expression was more frequently
      observed in patients with hepatic versus neurologic presentation (79% vs. 30%,
      p<0.05). Furthermore, GP73 expression was significantly higher (44.7+/-14.0 vs.
      2.0+/-0.81, p<0.05) in patients with hepatic phenotype. In Atp7b(-/-) mice, GP73
      mRNA was significantly elevated at 20-46 weeks of age, coincident with extensive
      hepatic inflammation and fibrosis, but not at 6 weeks, when hepatic histology was
      normal despite significant copper overload. GP73 mRNA levels normalized
      concomitantly with the resolution of hepatic injury at 60-weeks. However, in
      tumor-like nodules GP73 was strikingly elevated. CONCLUSION: Increased hepatocyte
      GP73 expression is more commonly a feature of hepatic than neurologic WD, and is
      triggered in response to inflammation, fibrosis, and dysplasia, rather than
      copper overload.

PMID- 19596476
TI  - Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct
      ligation.
AB  - BACKGROUND/AIMS: The endocannabinoid system in mice plays a role in models of
      human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We
      report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive
      constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model
      of chronic liver disease. METHODS: CBD (5mg/kg; i.p.) was administered over
      4weeks to mice that had undergone BDL. RESULTS: Cognitive function in the eight
      arm maze and the T-maze tests, as well as locomotor function in the open field
      test were impaired by the ligation and were improved by CBD. BDL raised
      hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by
      CBD. However, BDL reduced expression of the brain-derived neurotrophic factor
      (BDNF) gene, which was increased by CBD. The effects of CBD on cognition,
      locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an
      A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.
      CONCLUSIONS: The effects of BDL apparently result in part from down-regulation of
      A(2)A adenosine receptor. CBD reverses these effects through activation of this
      receptor, leading to compensation of the ligation effect.

PMID- 19596477
TI  - Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells.
AB  - BACKGROUND/AIMS: Co-infection with hepatitis B virus (HBV) and hepatitis C virus
      (HCV) increases the risk of development and the severity of chronic liver
      disease. Although dominant and suppressive effects of each virus over the other
      have been reported in vivo, in vitro studies of HBV/HCV co-infection have been
      limited to analysis of the effects of over-expression of HCV proteins on HBV
      replication. METHODS: We have re-examined HBV/HCV interactions in Huh-7 cells
      following co-infection with cell culture-propagated HCV (HCVcc; genotype 2a) and
      a recombinant adenovirus vector capable of delivering a replication-competent HBV
      genome (AdHBV; genotype A). RESULTS: While intracellular HCV RNA levels were
      significantly increased when cells were pre-infected with AdHBV, HCV replication
      and virion secretion were not altered by simultaneous infection with AdHBV or
      AdHBV superinfection of HCV-infected cells. Likewise intracellular and secreted
      HBV DNA levels and HBV promoter activities were either unchanged or modestly
      increased by HCVcc infection. Despite this, HCV E2 and HBsAg proteins colocalized
      extensively in co-infected cells suggesting shared stages in viral egress.
      CONCLUSIONS: These studies indicate that there is little direct interaction of
      HBV and HCV in co-infected hepatocytes and imply that indirect effects of host
      viral interactions dictate viral dominance in HBV/HCV co-infected individuals.

PMID- 19596478
TI  - Liver transplantation for glycogen storage disease type Ia.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) most often occurs within
      hepatocellular adenomas (HCAs) in glycogen storage disease Ia (GSD Ia) patients.
      The objective of this retrospective study is to assess outcomes after liver
      transplantation (LT) for GSD Ia where the principal indication for
      transplantation was prevention of HCC. METHODS: Petitions to the United Network
      for Organ Sharing region 11 review board for additional model for end-stage liver
      disease listing points were made on behalf of GSD Ia patients. Demographics, pre
      operative comorbidity, and outcomes for GSD Ia patients who underwent LT were
      reviewed. RESULTS: Between 2004 and 2006, five GSD Ia patients underwent LT.
      Multiple HCAs with focal hemorrhage and/or necrosis but without histological
      evidence of malignancy were identified in all explanted specimens. Four of five
      patients had complications after LT, including cytomegalovirus (CMV) infections
      and steroid responsive allograft rejection. Hemoglobin levels and serum
      triglyceride, total cholesterol, blood glucose, and lactic acid concentrations
      improved in all patients after LT. Corn starch feeding was not required in any
      patient after LT. Renal function worsened in three patients despite modifications
      to primary immunosuppressive medications. All patients are alive at last follow
      up (range 25-48 months) and all post-transplant complications have resolved.
      CONCLUSIONS: By removing all possible adenomatous tissue and reversing the
      underlying hepatic enzymatic deficiency, LT provides definitive prevention
      against HCC and correction of most metabolic derangements in GSD Ia patients.
      Renal dysfunction secondary to GSD Ia persists--underscoring the need for further
      studies to better understand the mechanisms of renal dysfunction in these
      patients.

PMID- 19596479
TI  - New insights into hepatitis B and C virus co-infection.

PMID- 19596480
TI  - Immunization against hepatitis C virus with a fusion protein containing the extra
      domain A from fibronectin and the hepatitis C virus NS3 protein.
AB  - BACKGROUND/AIMS: Vaccination strategies able to induce strong T-cell responses
      might contribute to eradicate hepatitis C virus (HCV) infection. We previously
      demonstrated that fusion of an antigen to the extra domain A from fibronectin
      (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves
      its immunogenicity. Here, we studied if fusion of EDA with the non-structural HCV
      protein NS3 might constitute an effective immunogen against HCV. METHODS:
      Recombinant NS3 and the fusion protein EDA-NS3 were produced and purified from E.
      coli, and tested in vitro for their capacity to activate maturation of DC and to
      favour antigen presentation. HHD transgenic mice expressing the human HLA-A2
      molecule were immunized with recombinant proteins in the absence or presence of
      poly(I:C) and anti-CD40 agonistic antibodies and responses elicited by
      vaccination were tested in vitro, and in vivo, by their capacity to downregulate
      intrahepatic expression of HCV-NS3 RNA. RESULTS: EDA-NS3, but not NS3 alone,
      upregulated the expression of maturation markers, as well as Delta-like 1 and
      Delta-like 4 Notch ligands in DC and induced the production of IL-12. Mice
      immunized with EDA-NS3 had strong and long lasting NS3-specific CD4+ and CD8+ T
      cell responses and, in combination with poly(I:C) and anti-CD40, downregulated
      intrahepatic expression of HCV-NS3 RNA. CONCLUSIONS: Recombinant EDA-NS3 may be
      considered for the development of vaccines against HCV infection.

PMID- 19596481
TI  - Developmental genome rearrangements in ciliates: a natural genomic subtraction
      mediated by non-coding transcripts.
AB  - Several classes of non-protein-coding RNAs have recently been identified as
      epigenetic regulators of developmental genome rearrangements in ciliates,
      providing an interesting insight into the role of genome-wide transcription. In
      these unicellular eukaryotes, extensive rearrangements of the germline genome
      occur during the development of a new somatic macronucleus from the germline
      micronucleus. Rearrangement patterns are not dictated by the germline sequence,
      but reproduce the pre-existing rearrangements of the maternal somatic genome,
      implying a homology-dependent global comparison of germline and somatic genomes.
      We review recent evidence showing that this is achieved by a natural genomic
      subtraction, computed by pairing interactions between meiosis-specific, germline
      scnRNAs (small RNAs that resemble metazoan piRNAs) and longer non-coding
      transcripts from the somatic genome. We focus on current models for the RNA-based
      mechanisms enabling the cell to recognize the germline sequences to be eliminated
      from the somatic genome and to maintain an epigenetic memory of rearrangement
      patterns across sexual generations.

PMID- 19596483
TI  - Clinical significance of NQO1 C609T polymorphisms after postoperative radiation
      therapy in completely resected non-small cell lung cancer.
AB  - PURPOSE: To investigate the clinical significance of NQO1 C609T polymorphisms to
      treatment outcome after postoperative radiation therapy in completely resected
      non-small cell lung cancer (NSCLC). METHODS: One hundred and sixteen, Korean
      ethnic, patients who were treated with surgery and postoperative radiation
      therapy from February 2000 to September 2005 in Asan Medical Center (Seoul, South
      Korea) were analyzed. All patients received 5040cGy radiation to surgical stump,
      mediastinum and ipsilateral supraclavicular node. NQO1 C609T polymorphisms were
      examined from a peripheral blood sample in all patients. Three types of NQO1
      C609T polymorphisms were designated as C/C, C/T and T/T. Chest computed
      tomography was routinely checked after radiation therapy at every 3 or 6 months
      and locoregional tumor control, distant metastasis and survival by NQO1 C609T
      genotype were analyzed. RESULTS: The proportion of NQO1 C609T polymorphisms was
      27.6% for C/C, 53.4% for C/T and 19.0% for T/T. Most patients were men and had
      squamous cell carcinoma or adenocarcinoma. Median age of patients was 61 years.
      Major failure pattern was distant metastasis and 13 (11.2%) patients showed
      locoregional recurrence within the field of previous radiation therapy. Crude
      locoregional recurrence rate was significantly different by NQO1 genotype; 6.3%
      in C/C, 8.1% in C/T, and 27.3% in T/T (p=0.03), but distant metastasis was not
      different. Median follow-up time was 49.2 months (range: 3.4-103.5 months).
      Locoregional recurrence-free survival (LRRFS) was affected in T/T genotype
      compared with C/C or C/T genotype (p=0.01, Kaplan-Meier method), but distant
      metastasis-free survival (DMFS) or overall survival (OS) was not different by
      NQO1 genotype in univariate analysis. NQO1 genotype was also a significant factor
      for LRRFS (p=0.01) in multivariate analysis. Radiation-induced pneumonitis or
      esophagitis was tolerable in all patients and the difference by NQO1 genotype was
      not observed. CONCLUSIONS: NQO1 C609T polymorphisms could be a predictive factor
      for the locoregional tumor control after postoperative radiation therapy in
      completely resected NSCLC.

PMID- 19596482
TI  - What controls nucleosome positions?
AB  - The DNA of eukaryotic genomes is wrapped in nucleosomes, which strongly distort
      and occlude the DNA from access to most DNA-binding proteins. An understanding of
      the mechanisms that control nucleosome positioning along the DNA is thus
      essential to understanding the binding and action of proteins that carry out
      essential genetic functions. New genome-wide data on in vivo and in vitro
      nucleosome positioning greatly advance our understanding of several factors that
      can influence nucleosome positioning, including DNA sequence preferences, DNA
      methylation, histone variants and post-translational modifications, higher order
      chromatin structure, and the actions of transcription factors, chromatin
      remodelers and other DNA-binding proteins. We discuss how these factors function
      and ways in which they might be integrated into a unified framework that accounts
      for both the preservation of nucleosome positioning and the dynamic nucleosome
      repositioning that occur across biological conditions, cell types, developmental
      processes and disease.

PMID- 19596484
TI  - Changes in organic acid metabolism differ between roots and leaves of Citrus
      grandis in response to phosphorus and aluminum interactions.
AB  - Seedlings of sour pummelo (Citrus grandis) were irrigated daily for 18 weeks with
      nutrient solution containing four phosphorus (P) levels (50, 100, 250 and 500
      microM KH2PO4) and two aluminum (Al) levels [0 (-Al) and 1.2 mM AlCl3 x 6H2O
      (+Al)]. Both malate and citrate concentrations in +Al leaves decreased with
      increasing P supply, but their concentrations in -Al leaves did not change in
      response to P supply. The concentrations of malate under 50 microM P and of
      citrate under 50 and 100 microM P were higher in +Al leaves than in -Al ones, but
      malate concentration was lower in +Al leaves than in -Al ones under 500 microM P.
      There was no difference in root malate and citrate concentrations among different
      P and Al combinations except for an increase in malate and citrate under 50
      microM P+0 mM Al and a slight decrease in malate under 50 microM P+1.2 mM Al. The
      activities of acid-metabolizing enzymes (citrate synthase, aconitase,
      phosphoenolpyruvate carboxylase, NADP-isocitrate dehydrogenase,
      phosphoenolpyruvate phosphatase, NAD-malate dehydrogenase, NADP-malic enzyme and
      pyruvate kinase) in most cases were less affected by P and Al interactions in
      roots compared to the leaves. Our results support the hypothesis that changes in
      organic acid metabolism differ between roots and leaves of C. grandis in response
      to P and Al interactions.

PMID- 19596485
TI  - [Visual field progression after trabeculectomy in primary open-angle glaucoma:
      preliminary results].
AB  - INTRODUCTION: Our purpose was to evaluate the changes in the visual field (VF)
      after trabeculectomy and to indentify factors influencing variation for a better
      follow-up of patients with primitive open-angle glaucoma (POAG). MATERIAL AND
      METHODS: We conducted a prospective study at the A. Le Dantec Hospital in Dakar,
      Senegal. Seventeen eyes of POAG patients were studied. The parameters noted for
      each patient were age, sex, affected eye, pre- and postoperative intra-ocular
      pressure (IOP), cup disk, sensitivity thresholds on pre- and postoperative
      perimetry, severity of glaucoma, and medication taken by the patient. Each
      patient had a frequency doubling technology (FDT) visual field examination before
      and the after surgery. None of them had an associated pathology that could cause
      VF troubles. The postoperative visual field was noted. All these parameters were
      correlated using the chi square test in order to determine factors influencing a
      threshold variation. RESULTS: Our patients were new in 70.6% of cases, and the
      mean age was 45 years. The mean preoperative IOP was 25.7mmHg, 29.4% of the eyes
      had a cup disk up to 0.7. The VF showed severe glaucoma in 58.8%; 70.6% of eyes
      had only beta-blocker treatment. Peritomy with limbic hinge was performed in
      88.2% of trabeculectomies. No surgical complication was noted. After
      trabeculectomy, the mean IOP was 14mmHg with a mean decrease of 42.8%. Before
      surgery, 94.1% of eyes had lower temporal quadrant involvement. For 94.1% of
      eyes, central vision was preserved. After surgery, progression was better in 18%,
      stable in 41%, and worse in 41% of cases. Of the factors studied, only age and
      graded follow-up time from surgery had a statistically significant influence on
      VF after trabeculectomy. CONCLUSION: Trabeculectomy was necessary in treatment of
      POAG, because of poor observance of medical treatment and severity of lesions at
      the time of diagnosis. The results (59% improvement or stability), in spite of
      the small sample size, argue in favor of this surgical treatment for some
      patients with POAG in our country.

PMID- 19596486
TI  - [Choroidal osteoma associated with cystoid macular edema].

PMID- 19596488
TI  - Meticillin-resistant Staphylococcus aureus epidemiology and transmission in a
      Dutch hospital.
AB  - The application of the search and destroy (S&D) policy in Scandinavian and Dutch
      hospitals is associated with low rates of meticillin-resistant Staphylococcus
      aureus (MRSA). The objective of our study was to describe the MRSA epidemiology
      and transmission in a Dutch hospital. This descriptive study was performed in a
      teaching hospital with approximately 40,000 admissions per year. In this hospital
      the MRSA S&D policy has been applied for several decades. MRSA epidemiology was
      studied during the years 2001 to 2006. The transmission rate in this hospital was
      determined using (1) patient's history, (2) relation in time and place to other
      patients or healthcare workers (HCWs), and (3) molecular typing (pulsed-field gel
      electrophoresis and Spa). Ninety-five persons were identified as MRSA carriers,
      namely 82 patients and 13 HCWs. The annual MRSA incidence increased more than
      three-fold during the study period, which was entirely caused by animal-related
      MRSA. Twenty-three percent of the patients acquired MRSA in a foreign hospital,
      26% via animals, 16% by nosocomial transmission, 4% in another Dutch healthcare
      institution, 10% in the community via a known MRSA-positive person, and in 22%
      the source was unknown. For HCWs, 69% of MRSA was due to nosocomial transmission,
      15% was related to working in a foreign hospital and in 15% HCWs became colonised
      via an MRSA-positive partner or relative. The transmission rate of 0.30 (22
      secondary cases from 73 index cases) indicates that the spread of MRSA was under
      control during the study period, and so the S&D policy should be continued.

PMID- 19596487
TI  - Exposure to mass media health information, skin cancer beliefs, and sun
      protection behaviors in a United States probability sample.
AB  - BACKGROUND: The mass media is increasingly important in shaping a range of health
      beliefs and behaviors. OBJECTIVE: We examined the association among mass media
      health information exposure (general health, cancer, sun protection information),
      skin cancer beliefs, and sun protection behaviors. METHODS: We used a general
      population national probability sample comprised of 1633 individuals with no skin
      cancer history (Health Information National Trends Survey, 2005, National Cancer
      Institute) and examined univariate and multivariate associations among family
      history of skin cancer, mass media exposure, skin cancer beliefs, and sun
      protection (use of sunscreen, shade seeking, and use of sun-protective clothing).
      RESULTS: Mass media exposure was higher in younger individuals, and among those
      who were white and more highly educated. More accurate skin cancer beliefs and
      more adherent sun protection practices were reported by older individuals, and
      among those who were white and more highly educated. Recent Internet searches for
      health or sun protection information were associated with sunscreen use.
      LIMITATIONS: Study limitations include the self-report nature of sun protection
      behaviors and cross-sectional study design. CONCLUSION: We identify demographic
      differences in mass media health exposure, skin cancer beliefs, and sun
      protection behaviors that will contribute to planning skin cancer awareness and
      prevention messaging across diverse population subgroups.

PMID- 19596489
TI  - Impact of hypochlorite-based disinfection on bacterial contamination of cystic
      fibrosis patients' home-nebulisers.
AB  - Nebulisers are a potential source of bacterial contamination in cystic fibrosis
      (CF) patients. The aims of the study were to survey patient practice regarding
      maintenance of home nebulisers and to assess the impact of standardised
      guidelines derived from a previous in-vitro study. In total, 42 CF patients were
      studied. During two consecutive home visits, a questionnaire regarding routine
      patient practice was completed by a nurse while sputum and equipment samples were
      taken for bacteriological analyses. The first visit took place at baseline, and
      the second followed the implementation of detailed instructions for cleaning and
      disinfecting the nebulisers using a 0.5% hypochlorite solution. The first visit
      identified a great diversity in routine patient practices. Commensal bacteria,
      environmental bacteria and potential CF pathogens contaminated 78.5%, 57.1% and
      14.3% of nebulisers respectively. After hypochlorite disinfection, rate and
      degree of global contamination decreased significantly, but the number of CF
      pathogens was not affected. There was no concordance between CF pathogens
      isolated from patients' sputum and their equipment. We conclude that in this
      sample of patients, initial routine practices were varied. With regard to CF
      pathogens, the superiority of a hypochlorite solution over a mix of other
      disinfection methods was not demonstrated.

PMID- 19596490
TI  - Automated system to identify Clostridium difficile infection among hospitalised
      patients.
AB  - The purpose of this study was to assess whether data on stool frequency collected
      electronically could identify patients at high risk for Clostridium difficile
      infection (CDI). All patients with reports of diarrhoea were assessed
      prospectively for number of stools per day and number of diarrhoea days. C.
      difficile testing was requested independently from study investigators. Number of
      days with diarrhoea and maximum number of unformed stools was assessed as a CDI
      predictor. A total of 605 patients were identified with active diarrhoea of whom
      64 (10.6%) were diagnosed with CDI. In univariate analysis, the maximum number of
      stools and number of diarrhoea days was associated with increased risk of CDI.
      Compared to patients with three diarrhoea stools per day (CDI incidence: 6.3%),
      CDI increased to 13.4% in patients with four or more diarrhoea stools per day
      [odds ratio (OR): 2.3; 95% confidence interval (CI): 1.3-4.2; P=0.0054]. Compared
      to patients with one day of diarrhoea (CDI incidence: 6.3%), CDI increased to
      17.4% in patients with two diarrhoea days (OR: 3.1; 95% CI: 1.7-5.6) and to 27.1%
      in patients with three or more diarrhoea days (OR: 5.5; 95% CI: 2.6-11.7). These
      results were validated using logistic regression with number of days with
      diarrhoea identified as the most important predictor. Using an electronic data
      capture technique, number of days of diarrhoea and maximum number of diarrhoea
      stools in a 24h time period were able to identify a patient population at high
      risk for CDI.

PMID- 19596491
TI  - Extended-spectrum beta-lactamase-producing organisms.
AB  - Extended-spectrum beta-lactamases (ESBLs), which hydrolyse extended-spectrum
      cephalosporins and are inhibited by clavulanic acid, are spreading among
      Enterobacteriaceae. The CTX-M enzymes are replacing SHV and TEM enzymes as the
      prevalent type of ESBLs, principally in community-acquired infections caused by
      Escherichia coli. Associated infectious syndromes include mainly urinary tract
      infections, and secondly bloodstream and intra-abdominal infections, and may be
      serious enough to warrant hospitalisation. Affected patients commonly have
      various underlying risk factors. This is also observed in hospital-acquired
      infections. The rates of ESBL-expression among nosocomial Enterobacteriaceae
      isolates, particularly Klebsiella pneumoniae, have risen substantially in several
      countries. The hospital epidemiology of these infections is often complex;
      multiple clonal strains causing focal outbreaks may co-exist with sporadic ones.
      Relevant infection-control measures should focus on reducing patient-to-patient
      transmission via the inanimate environment, hospital personnel, and medical
      equipment. Wise use of antibiotics is also essential. The available therapeutic
      options for the treatment of ESBL-associated infections are limited by drug
      resistance conferred by the ESBLs, along with frequently observed co-resistance
      to various antibiotic classes, including cephamycins, fluoroquinolones,
      aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole. Relevant
      clinical data regarding the effectiveness of different regimens for ESBL
      associated infections are limited. Although certain cephalosporins may appear
      active in vitro, associated clinical outcomes are often suboptimal. beta
      Lactam/beta-lactamase inhibitor combinations may be of value, but the supporting
      evidence is weak. Carbapenems are regarded as the agents of choice, and may be
      more effective than fluoroquinolones for serious infections. Tigecycline and
      polymyxins have substantial antimicrobial activity against ESBL-producing
      Enterobacteriaceae, and, along with fosfomycin, merit further evaluation.

PMID- 19596492
TI  - Evaluation of the bactericidal efficacy of three different alcohol hand rubs
      against 57 clinical isolates of S. aureus.
AB  - We tested the efficacy of three alcohol hand rubs (AHRs) used in two local Welsh
      intensive therapy units (ITUs) against Staphylococcus aureus. The test protocol
      was based on a carrier test and parameters (concentration, contact time) were
      chosen following observation of hand-sanitising practices in the ITUs. Following
      AHR exposure, surviving bacteria were enumerated using a standard plate count
      method plus a Bioscreen C Microbial Growth Analyser. The AHRs demonstrated
      variable efficacy against the clinical isolates: the mean log(10) reduction after
      10 s exposure to Soft Care Med H5, Cutan and Guest Medical AHRs was 2.67, 0.696
      and 1.96, respectively, and after 30 s exposure was 4.58, 1.74 and 3.60,
      respectively. Since the average time taken by healthcare workers (HCWs) to rub
      AHR onto their hands was 11 s and 15 s at the two hospitals, the efficacy of
      these AHRs may be significantly limited against the S. aureus isolates under the
      conditions observed in practice. In addition, differences observed in log(10)
      reduction in bacterial number post-exposure using the Bioscreen compared to the
      plate count method provided evidence that S. aureus may be able to recover
      following Guest Medical AHR treatment within 2 min exposure, whereas after 5 min
      exposure bacterial damage caused by the AHR was irreversible. Although the
      introduction of AHRs improved hand hygiene compliance among HCWs, our
      observations highlighted that contact time is an important factor to ensure the
      efficacy of these products.

PMID- 19596493
TI  - Community-associated meticillin-resistant Staphylococcus aureus: epidemiology,
      microbiology and clinical impact in East Yorkshire, UK.
AB  - The prevalence of community-associated meticillin-resistant Staphylococcus aureus
      (CA-MRSA) is increasing worldwide. Whilst CA-MRSA has been reported in the UK,
      there is little information concerning its clinical impact. Here we report three
      epidemic lineages of CA-MRSA occurring in East Yorkshire and describe their
      epidemiology, microbiology and clinical impact. Although CA-MRSA was most often
      associated with uncomplicated skin and soft tissue infections or asymptomatic
      colonisation, serious infection and fatalities were documented. Community-based
      transmission was noted in two separate households. We highlight limitations to
      existing definitions and propose debate to further define CA-MRSA and allow
      further study of its epidemiology and clinical impact in the UK.

PMID- 19596494
TI  - Controversies in infection: infection control or antibiotic stewardship to
      control healthcare-acquired infection?
AB  - Despite record resource being devoted to the control of healthcare-acquired
      infection (HCAI), rates have never been higher. Although the discovery of the
      contagiousness of puerperal sepsis by Alexander Gordon heralded the golden era of
      bacteriology and antibiotics, this led to a belief that infection was beaten.
      This in its turn may well have led us into a false sense of security and an over
      reliance on antibiotics. Modern medicine has built many of its advances on a need
      for antibiotics, but their very success has led to huge over-use and resulting
      problems of resistance. Compounded by the absence of a good antibiotic pipeline
      we are now being forced to address the paradox of antibiotics; namely that they
      may actually be causing many HCAIs. Not only Clostridium difficile infection, but
      many others such as those caused by meticillin-resistant Staphylococcus aureus,
      are more or less completely contingent on antibiotic prescribing. Control of
      prescribing would probably be just as effective a measure in our fight against
      HCAI as conventional infection control measures. Arguably, traditional infection
      control is akin to fire-fighting and antibiotic stewardship to prevention.

PMID- 19596495
TI  - [Internet and associated factors in adolescents in the Community of Madrid].
AB  - OBJECTIVE: To determine the type of Internet use carried out by adolescent
      schoolchildren and identify factors associated with high use. DESIGN:
      Descriptive, cross-sectional study using a self-administered questionnaire.
      SETTING: Secondary and High School Education Centres of the Autonomous Community
      of Madrid (rural and urban areas). PARTICIPANTS: Third and fourth year Secondary
      and 1st and 2nd year High School pupils from 9 centres. A total of 1328 of the
      1330 pupils present in the classrooms during the school term January-April 2007.
      PRINCIPAL MEASUREMENTS: Dependent variable: intensity of Internet use: very high,
      high, medium, low and none. Information on socioeconomic variables, smoking,
      drugs and drinking habits, mental health, academic failure and use of mobile
      telephone. An analysis was made using a two-step logical regression. RESULTS: The
      mean age of the sample was 15 years, with an equal number of males and females. A
      total of 93.1% used the Internet, of which 5.3% (95% CI: 4-6.5%) had a very high
      use, 16.7% (95% CI: 14.5-18.6%) high use, 71.1% (95% CI: 68.2-73.2%) low to
      medium use, and 6.9% (95% CI: 5.6-8.4%), did not use it. Very high use of the
      Internet is associated with the male sex (OR=4.28;95% CI:2.37-7.72), being 16
      years or over (OR=2.14;95% CI:1.23-3.72) and is dependent on the mobile phone
      (OR=5.19;95% CI: 2.97-9.08). An association with alcohol consumption was observed
      in the high use group (OR=1.89; 95% CI:1,35-2,65). Academic failure is more
      common among those who do not use the Internet (OR=1.61; 95% CI:1.02-2.55).
      CONCLUSIONS: Given the relationship found between high Internet use and mental
      health problems and bad habits, it is important to perfect standardised tools to
      detect and evaluate the compulsive use of the Internet as well as aid to its
      responsible use.

PMID- 19596497
TI  - Effects of radionuclide and rainfall characteristics on field loss parameters of
      grass.
AB  - The decrease of foliar activity in vegetation after its initial contamination by
      foliar deposition is termed "field loss" (Chamberlain, 1970). This work
      investigated further laboratory data concerning field loss of (134)Cs, (137)Cs,
      (85)Sr, (133)Ba and (123m)Te deposited on grassland (Madoz-Escande et al., 2005).
      Treatments consisted in rainfall scenarios cumulating 14 mm per week, combining
      two levels of intensity (8 or 30 mm/h) and two levels of frequency/precocity
      (late once or early twice-a-week). The time course of field loss was monitored in
      the edible tissues which were sampled by mowing between the rainfalls. Data were
      analyzed with an offset exponential loss model which is applicable to chronic
      contamination and is consistent with approaches adopted in radiological
      assessment models. Its parameters were estimated by the maximum-likelihood
      method, and their accuracy was determined by nonparametric bootstrap.
      Radionuclide and rainfall conditions significantly affected the estimated rate
      (lambda(1)) and extent (A(1)) of field loss. Field loss rate (lambda(1)) and
      nonentrainable fraction (1-A(1)) varied by a factor 1.5-3. Cesium was very mobile
      but persistent. On the contrary Tellerium was found less labile, but eventually
      was almost completely eliminated. Strontium and Barium had intermediate
      behaviors. Field loss was more efficient for moderate late once-a-week rainfalls
      (8mm/h). Higher rainfall intensity reduced more the radionuclides losses than
      higher rainfall frequency/precocity. This paper reports statistically relevant
      effects that should be considered for more realistic assessments.

PMID- 19596496
TI  - [Diagnostic resources for sexually transmitted infections in laboratories in
      Catalonia (Spain)].
AB  - OBJECTIVE: With the aim of describing both the capacity and organization of the
      laboratories in Catalonia to diagnose sexually transmitted infections, a cross
      sectional study was performed between November 2005 and March 2006, which
      included 140 laboratories. RESULTS: Ninety-eight laboratories performed some STI
      tests, 45 received more than 50 vaginal swabs per month, 42 diagnosed Chlamydia
      trachomatis, but only six used polymerase chain reaction techniques. None
      diagnosed venereal lymphogranuloma. Eighty were able to detect Neisseria
      gonorrhoeae, 76 by means of culture and 63 analyzed its antibiotic resistance. A
      total of 23, 22, 22 and 14 laboratories received more than 500 blood samples for
      hepatitis B, hepatitis C, HIV and syphilis, respectively. Non-treponemic and
      treponemic tests were available in 84 and 52 laboratories, respectively.
      CONCLUSIONS: In Catalonia, most STIs can be diagnosed but new technologies need
      to be introduced. Moreover, the efficiency of biological sample circuits should
      be improved.

PMID- 19596498
TI  - Experimental and theoretical studies on physico-chemical parameters affecting the
      solubility of phosphogypsum.
AB  - Phosphogypsum is a waste by-product of the phosphate fertilizer industry, which
      is usually disposed in the environment because of its restricted use in
      industrial applications. Physico-chemical conditions existing in stack fluids and
      leachates are of major importance and determine solubility and redox stability of
      phosphogypsum, as well as radionuclide release from stacks to terrestrial
      environments. The aim of this study is to assess the effect of key parameters
      (e.g. ionic strength, temperature, pH) on the solubility of phosphogypsum.
      Phosphogypsum sampling and in-situ measurements were carried out at a coastal
      stack in Cyprus, solubility experiments were performed in simulated laboratory
      systems and thermodynamic calculations by means of MINTEQA2, an equilibrium
      speciation model. Generally, increasing ionic strength and temperature leads to
      increased phosphogypsum solubility, with the former being much more effective.
      The increased solubility of phosphogypsum in saline solutions is attributed
      solely to ionic strength effects on the activity of ionic species in solution and
      no solid phase transformations could be observed. The effect of pH on
      phosphogypsum solubility seems to be insignificant at least in a pH range between
      4 and 8. Regarding uranium levels, there is a strong correlation between salinity
      and uranium concentration and linear correlation between phosphogypsum solubility
      and uranium levels in stack solutions, indicating the incorporation of uranium
      into the gypsum lattice and the formation of a solid solution.

PMID- 19596500
TI  - Temporary alopecia caused by pressure from a headband used to secure a reference
      frame to the head during navigational surgery.

PMID- 19596499
TI  - Postoperative monitoring of microsurgical free tissue transfers for head and neck
      reconstruction: a systematic review of current techniques.

PMID- 19596501
TI  - Fine needle aspiration of a neck lump: a mercurial mystery.
AB  - We describe an interesting case of mercury within a lymph node, which we found
      during routine fine needle aspiration cytology of a neck lump. We know of no
      similar reports and look for any suggestions from our readers as to the cause of
      such a finding.

PMID- 19596502
TI  - Bone engineering-vitalisation of alloplastic and allogenic bone grafts by human
      osteoblast-like cells.
AB  - Human osteoblasts on non-sintered hydroxyapatite and demineralised bone matrix
      (DBX) were analysed in vitro to find out whether they would be suitable for
      reconstruction of bones in oral surgery. Human osteoblasts were isolated from the
      jaw during routine dental operations and seeded onto the two biomaterials. Cells
      were characterised by assay of alkaline phosphatase, detection of type 1
      collagen, and production of osteocalcin. After 21 days of cultivation, the
      cell/biomaterial constructs were examined by scanning electron microscopy, thin
      sections, and propidium iodide/fluorescein diacetate staining. The osteoblasts
      formed a vital multiple cell layer on DBX within 3 weeks of cultivation. On
      hydroxyapatite, the cells showed no tendency to proliferate or migrate onto the
      synthetic biomaterial, or to form well-spread and viable cell constructs. These
      findings suggest that surface morphology or the presence of osteoinductive
      factors may have an important role in the adhesion and proliferation of
      osteoblasts. Human DBX can be colonised by human osteoblast-like cells in vitro,
      indicating the potential of allogeneic carriers for future procedures in bone
      engineering.

PMID- 19596503
TI  - Resilience and marginalized youth: making a case for personal and collective
      meaning-making as part of resilience research in public health.
AB  - The public health research community has long recognized the roles of
      discrimination, institutional structures, and unfair economic practices in the
      production and maintenance of health disparities, but it has neglected the ways
      in which the interpretation of these structures orients people in overcoming them
      and achieving positive outcomes in their lives. In this call for researchers to
      pay more - and more nuanced - attention to cultural context, we contend that
      group identity-as expressed through affiliation with an oppressed group-can
      itself prompt meaningful role-based action. Public health's study of resilience,
      then, must consider the ways that individuals understand and, in turn, resist
      discrimination. In this article, we briefly outline the shortcomings of current
      perspectives on resilience as they pertain to the study of marginalized youth and
      then consider the potential protection offered by ideological commitment. To
      ground our conceptual argument, we use examples from two different groups with
      whom the authors have worked for many years: indigenous and sexual minority
      youth. Though these groups are dissimilar in many ways, the processes related to
      marginalization, identity and resilience are remarkably similar. Specifically,
      group affiliation can provide a context to reconceptualize personal difficulty as
      a politicized collective struggle, and through this reading, can create a
      platform for ideological commitment and resistance.

PMID- 19596505
TI  - Remineralization of enamel subsurface lesions by chewing gum with added calcium.
AB  - OBJECTIVES: Chewing sugar-free gum has been shown to promote enamel
      remineralization. Manufacturers are now adding calcium to the gum in an approach
      to further promote enamel remineralization. The aim of this study was to compare
      the remineralization efficacy of four sugar-free chewing gums, two containing
      added calcium, utilizing a double-blind, randomized, crossover in situ model.
      METHODS: The sugar-free gums were: Trident Xtra Care, Orbit Professional, Orbit
      and Extra. Ten subjects wore removable palatal appliances with four human-enamel
      half-slab insets containing subsurface demineralized lesions. For four times a
      day for 14 consecutive days subjects chewed one of the chewing gums for 20min.
      After each treatment the enamel slabs were removed, paired with their respective
      demineralized control slabs, embedded, sectioned and mineral level determined by
      microradiography. After 1-week rest the subjects chewed another of the four gums
      and this was repeated until each subject had used the four gum products. RESULTS:
      Chewing with Trident Xtra Care resulted in significantly higher remineralization
      (20.67+/-1.05%) than chewing with Orbit Professional (12.43+/-0.64%), Orbit
      (9.27+/-0.59%) or Extra (9.32+/-0.35%). The form of added calcium in Trident Xtra
      Care was CPP-ACP and that in Orbit Professional calcium carbonate with added
      citric acid/citrate for increased calcium solubility. CONCLUSIONS: Although
      saliva analysis confirmed release of the citrate and calcium from the Orbit
      Professional gum the released calcium did not result in increased enamel
      remineralization over the normal sugar-free gums. These results highlight the
      importance of calcium ion bioavailability in the remineralization of enamel
      subsurface lesions in situ.

PMID- 19596506
TI  - Edge strength of indirect restorative materials.
AB  - OBJECTIVES: To evaluate the edge strength and fracture patterns of different all
      ceramic and indirect composite materials used in prosthodontic applications.
      METHODS: Fourteen rectangular-shaped samples (2-2.5 mm thick) were prepared of
      each of the following materials: BelleGlass NG (Kerr) (BG), fibre-reinforced
      BelleGlass/EverStick (Kerr/Stick Tech Ltd.) (BGES), Vita Mark II (Vita
      Zahnfabrik) (VMII), bilayered IPS e.max Ceram/CAD (Ivoclar-Vivadent) (Ceram/CAD),
      bilayered IPS e.max Ceram/ZirCAD (Ivoclar-Vivadent) (Ceram/ZirCAD) and unilayered
      IPS e.max CADLT (Ivoclar-Vivadent) (CADLT). Each group was further subdivided
      into seven subgroups (n=2) corresponding to different edge distances at which
      samples were loaded. Samples were tested with an edge strength machine (CK10,
      Engineering Systems, Nottingham, UK) using a diamond Vickers indenter. The force
      to-failure (N) was recorded and four readings were obtained per sample. The mode
      of failure was analysed microscopically. One-way ANOVA was used to detect
      differences in edge strength among the groups and correlation and regression
      analyses were used to detect the correlation between distance of loading and
      failure force. RESULTS: The mean values of edge strength (N) were 94.1 (11.2) for
      BG, 134.4 (10.9) for BGES, 50.5 (8.9) for VMII, 54.4 (7.5) for Ceram/CAD, 53.2
      (8.4) for Ceram/ZirCAD and 69.1 (9.1) for CADLT. Significant (p<0.05) strong
      positive linear correlations were found between the force-to-failure and edge
      distance among all groups. Three patterns of failure were identified: surface
      indentation without visible cracking, surface indentation with visible cracking
      and chipping. CONCLUSIONS: Indirect composite materials had better edge fracture
      behaviour than all-ceramic materials. The addition of fibres enhanced the
      performance of the resin-composite material. Fracture strength increased as the
      distance from the edge increased. Edge fracture was restricted to the veneer
      material in bilayared systems and therefore a stronger veneer material is
      recommended.

PMID- 19596507
TI  - To close or not to close? A systematic review and a meta-analysis of peritoneal
      non-closure and adhesion formation after caesarean section.
AB  - Many gynaecologists do not currently close the peritoneum after caesarean section
      (CS). Recently, several studies examining adhesion formation after repeat CS
      appear to favour closure of the peritoneum after caesarean section. We performed
      a systematic review of the current available evidence with regard to the long
      term outcome, mainly in terms of adhesion formation after closure versus non
      closure of peritoneum during CS. We undertook a literature search between January
      1995 and February 2008 using MEDLINE, Pubmed, EMBASE, Cochrane central controlled
      trials register and Cochrane pregnancy and childbirth group trials register. We
      also had searched all the references cited in the relevant studies. Both English
      and non-English language papers were included. Prospective studies which compared
      peritoneal closure versus non-closure during CS in terms of adhesion formation
      were included. Studies were included if they had a primary objective to examine
      adhesion formation in a repeat caesarean section, had a clear study design, had
      an adhesion scoring system, excluded patients who had adhesions in the primary
      caesarean section or interim surgeries after the primary caesarean section, and
      had no usage of anti-adhesion agents in the primary caesarean section.
      Retrospective studies which were performed by case-notes review alone, were
      excluded. Eleven studies were identified via our search strategy. Five were
      retrospective and six were prospective. Out of the eleven studies, three
      satisfied the inclusion criteria and were included (n=249); two studies were
      follow-ups of RCTs and one was not randomised. Out of 249 women included in the
      analysis, 110 had peritoneal closure during CS whereas the other 139 did not have
      peritoneal closure. Meta-analysis was performed using the two randomised studies
      plus (i) the unadjusted estimate from the non-randomised study and (ii) the
      reported adjusted estimate, adjusted for baseline differences in the groups. Non
      closure of the peritoneum during CS resulted in a significantly increased
      likelihood of adhesion formation in both meta-analyses--OR (95% CI): (i) 2.60
      (1.48-4.56) and (ii) 4.23 (2.06-8.69). This systematic review has demonstrated
      that according to current data in the literature, there is some evidence to
      suggest that non-closure of the peritoneum after caesarean section is associated
      with more adhesion formation compared to closure.

PMID- 19596508
TI  - Splenic artery aneurysm rupture in pregnancy.
AB  - Splenic artery aneurysm (SAA) is the commonest visceral artery aneurysm. It is
      diagnosed more frequently in younger women, with up to 95% presenting during
      pregnancy. Rupture is associated with a disproportionately high maternal and
      fetal mortality. We performed a literature search on the patient and SAA
      characteristics, clinical presentations, management and outcome of this serious
      complication. There were 32 patients in total with a mean age of 27.9 years
      (range 20-38). The mean SAA size was 2.25 cm (range 0.5-4 cm) and from the
      available data half of the ruptured SAA were 2 cm or less. Only one case (3.1%)
      was discovered incidentally, whilst the rest (96.9%) were found following
      rupture. The majority ruptured spontaneously. Most (62%) of the patients
      underwent SAA ligation and splenectomy. The maternal death rate was 21.9% (n=7),
      and fetal death rate was 15.6% (n=5). Most cases are not diagnosed until surgery
      following rupture. Ruptured SAA should be considered in the differential
      diagnosis of a pregnant patient with severe and unexplained abdominal pain.

PMID- 19596509
TI  - Estrogen and progesterone hormonal receptor expression in urothelial carcinoma of
      the bladder.

PMID- 19596510
TI  - Re: Brian M. Benway, Agnes J. Wang, Jose M. Cabello and Sam B. Bhayani. Robotic
      partial nephrectomy with sliding-clip renorrhaphy: technique and outcomes. Eur
      Urol 2009;55:592-9.

PMID- 19596511
TI  - An efficient and novel porous nanosilica supported TiO2 photocatalyst for
      pesticide degradation using solar light.
AB  - A latex polymer of styrene-acrylic acid emulsion is used as a template for the
      synthesis of novel porous nanosilica (PNS) material. TiO(2) is dispersed over PNS
      by solid state dispersion and the composite materials are characterized by XRD,
      nitrogen adsorption-desorption isotherms, SEM and TEM measurements. The
      photocatalytic activities of the composite TiO(2)/PNS catalysts are evaluated for
      degradation of isoproturon pesticide in water with different parameters under
      solar light. Furthermore, commercial pesticide solutions containing imidacloprid
      and phosphamidon were also degraded successfully with the composite system using
      the same developed conditions for isoproturon degradation. The 5 wt% TiO(2)/PNS
      is found to be active in the present investigation.

PMID- 19596512
TI  - Lightweight bricks manufactured from water treatment sludge and rice husks.
AB  - Novel lightweight bricks have been produced by sintering mixes of dried water
      treatment sludge and rice husk. Samples containing up to 20 wt.% rice husk have
      been fired using a heating schedule that allowed effective organic burn-out. Rice
      husk addition increased the porosity of sintered samples and higher sintering
      temperatures increased compressive strengths. Materials containing 15 wt.% rice
      husk that were sintered at 1100 degrees C produced low bulk density and
      relatively high strength materials that were compliant with relevant Taiwan
      standards for use as lightweight bricks.

PMID- 19596513
TI  - Electrokinetic remediation of arsenate spiked soil assisted by CNT-Co barrier-
      the effect of barrier position and processing fluid.
AB  - An enhanced electrokinetic (EK) remediation process coupled with permeable
      reaction barrier (PRB) of carbon nanotube coated with cobalt (CNT-Co) has been
      investigated for As(V) removal from soil under potential gradient of 2.0 V/cm for
      5 days treatment. Results showed that removal efficiency of As(V) was greater
      than 70% in EK/CNT-Co system with EDTA as processing fluid, which was enhanced by
      a factor of 2.2 compared to EK system and EK/CNT systems. A better removal
      performance in EK/CNT-Co system was attributed to higher sorption of As(V) onto
      CNT-Co than onto CNT. Removal of As(V) in EK/CNT-Co system was mainly contributed
      by surface sorption on CNT-Co rather than by EK process. The surface
      characteristics of CNT-Co, which was qualified by SEM coupled with EDS, were
      clearly confirmed that arsenic was adsorbed on the passive layer surface. Among
      EK processes, As(V) removal was dominated by electroosmosis flow and
      electromigration in EK/CNT-Co system with groundwater and EDTA as processing
      fluid. An investigation with sequential extraction revealed that As(V) associated
      with soils was considerably shifted from strong binding forms, i.e., Fe-Mn oxide,
      organic, and residual, to weak binding forms, i.e., exchange and carbonate, after
      EK/CNT-Co treatment.

PMID- 19596514
TI  - Development of a combined pyro- and hydro-metallurgical route to treat spent zinc
      carbon batteries.
AB  - The potential of solvent extraction using Cynanex272 for the recovery of zinc
      from spent zinc carbon batteries after a prior leaching in hydrochloric acid has
      been investigated. The elemental analysis of the spent material was carried out
      by ICP-MS. The major metallic elements are: ZnO (41.30%), Fe(2)O(3) (4.38%),
      MnO(2) (2.69%), Al(2)O(3) (1.01%), CaO (0.36%) and PbO (0.11%). The quantitative
      leaching by hydrochloric acid showed that the dissolution rates are significantly
      influenced by temperature and concentration of the acid solutions. The
      experimental data for the dissolution rates have been analyzed and were found to
      follow the shrinking core model for mixed control reaction with surface chemical
      reaction as the rate-determining step. About 90.3% dissolution was achieved with
      4M HCl solution at 80 degrees C with 0.050-0.063 mm particle size within 120 min
      at 360 rpm. Activation energy value of 22.78 kJ/mol and a reaction order of 0.74
      with respect to H(+) ion concentration were obtained for the dissolution process.
      An extraction yield of 94.23% zinc by 0.032M Cyanex272 in kerosene was obtained
      from initial 10 g/L spent battery leach liquor at 25+/-2 degrees C and at optimal
      stirring time of 25 min. Iron has been effectively separated by precipitation
      prior to extraction using ammoniacal solution at pH 3.5, while lead and other
      trace elements were firstly separated from Zn and Fe by cementation prior to iron
      removal and zinc extraction. Finally, the stripping study showed that 0.1M HCl
      led to the stripping of about 95% of zinc from the organic phase.

PMID- 19596515
TI  - Effect of oil refinery sludges on the growth and antioxidant system of alfalfa
      plants.
AB  - The refining process in the petrochemical industry generates oil refinery
      sludges, a potentially contaminating waste product, with a high content of
      hydrocarbons and heavy metals. Faster degradation of hydrocarbons has been
      reported in vegetated soils than in non-vegetated soils, but the impact of these
      contaminants on the plants physiology and on their antioxidant system is not well
      known. In this study, the effect of the addition of petroleum sludge to soil on
      the physiological parameters, nutrient contents, and oxidative and antioxidant
      status in alfalfa was investigated. An inhibition of alfalfa growth and an
      induction of oxidative stress, as indicated by an increase in protein oxidation,
      were found. Also, the superoxide dismutase isoenzymes, peroxidase, and those
      enzymes involved in the ascorbate-glutathione cycle showed significant activity
      increases, parallel to an enhancement of total homoglutathione, allowing plants
      being tolerant to this situation. This information is necessary to establish
      successful and sustainable plant-based remediation strategies.

PMID- 19596516
TI  - Phosphorus removal of rural wastewater by the paddy-rice-wetland system in Tai
      Lake Basin.
AB  - A field experiment was conducted to remove the potential eutrophication effect of
      P from rural wastewater (RW) during the whole rice growing season of 2007. The
      experiments consisted of five treatments, namely black water (BW), domestic
      wastewater (DW), grey water (GW), surface lake water (SW) and surface lake water
      without P application as a check (CK), with three replicates in a randomized
      block design. Commercial fertilizer and RW were applied to furnish 40 kg Pha(-1)
      except CK. Results showed total P (TP) concentration had significantly declined
      after P application, from October 15 there were no significant increases in TP
      concentration in the floodwater. TP removal rates from RW was significantly
      higher (P<or=0.05) than those from fertilizer. TP load was in an overall gradual
      decline, whereupon it became approximately steady on October 1. The percentage of
      TP load from wastewater decreased, whereas that from fertilizer continued to
      increase. Meanwhile, the yield for CK was significantly less (P<or=0.05) than SW,
      GW, DW, and BW, with the yield of BW significantly greater (P<or=0.05) than other
      treatments. It is feasible to remove P from RW by the paddy-rice-wetland system
      and can be widely used to improve the yield of rice.

PMID- 19596518
TI  - Hypnosis for chronic pain management: a new hope.

PMID- 19596517
TI  - Removal of Cu(II) in aqueous media by biosorption using water hyacinth roots as a
      biosorbent material.
AB  - Water hyacinth roots were employed as a biosorbent to remove Cu(II) in aqueous
      media. Nitrogen adsorption/desorption analysis revealed that the biosorbent was
      mesoporous with a relatively small surface area. Equilibrium biosorption
      isotherms showed that the water hyacinth roots possessed a high affinity and
      sorption capacity for Cu(II) with a monolayer sorption capacity of 22.7 mg g(-1)
      at initial pH 5.5. Kinetics study at different temperatures revealed that the
      sorption was a rapid and endothermic process. The activation energy for Cu(II)
      sorption was estimated to be 30.8 kJ mol(-1), which is typical of activated
      chemisorption processes. The sorption mechanism was investigated by Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy, effect of pH
      and calcium release. These analyses suggested that the biosorption mainly
      involved the ion exchange of Cu(II) with cations and complex formation with
      functional groups on the surface of the roots. All the results showed that water
      hyacinth roots are an alternative low-cost biosorbent for the removal of Cu(II)
      from aqueous media.

PMID- 19596519
TI  - Bronchopulmonary nematode infection of Capra pyrenaica in the Sierra Nevada
      massif, Spain.
AB  - The present investigation examined the prevalence and abundance of
      bronchopulmonary nematodes in 213 randomly hunted Iberian ibexes (Capra
      pyrenaica) (87 females and 126 males) in the Sierra Nevada mountain range in
      Spain between 2003 and 2006. Post mortem examination revealed an overall
      prevalence of 72% for adult nematodes (Cystocaulus ocreatus 44%, Muellerius
      capillaris 44%, Protostrongylus sp. 40%, and Dictyocaulus filaria 4%). The
      abundances were 13.45+/-3.97, 5.18+/-2.49, 6.36+/-2.16, and 2.27+/-0.46,
      respectively. Protostrongylid adults showed similar infection rates, which were
      statistically different from that of D. filaria. 20% of the examined Iberian
      ibexes were infected by three protostrongylid nematodes species, 24% of C.
      pyrenaica were affected by two protostrongylid species, while infestations with
      only one protostrongylid species were detected in 20% of the examined animals.
      The overall prevalence of larvae nematodes in the examined animals was 100%, and
      the overall abundance (number of the first stage larvae per gram) was 86.45+/
      20.63. There was a high correlation between the two sets of data (adults and
      larvae). Results of the present investigation provided foundation for the
      effective control of bronchopulmonary nematode infection in Iberian ibex.

PMID- 19596520
TI  - Lousicidal, ovicidal and repellent efficacy of some essential oils against lice
      and flies infesting water buffaloes in Egypt.
AB  - The lousicidal and repellent effects of five essential oils were investigated for
      the first time against the buffalo louse, Haematopinus tuberculatus, and flies
      infesting water buffaloes in Qalyubia Governorate, Egypt. For the in vitro
      studies, filter paper contact bioassays were used to test the oils and their
      lethal activities were compared with that of d-phenothrin. Four minutes post
      treatment, the median lethal concentration, LC50, values were 2.74, 7.28, 12.35,
      18.67 and 22.79% for camphor (Cinnamomum camphora), onion (Allium cepa),
      peppermint (Mentha piperita), chamomile (Matricaria chamomilla) and rosemary oils
      (Rosmarinus officinalis), respectively, whereas for d-phenothrin, it was 1.17%.
      The lethal time (50) (LT50) values were 0.89, 2.75, 15.39, 21.32, 11.60 and 1.94
      min after treatment with 7.5% camphor, onion, peppermint, chamomile, rosemary and
      d-phenothrin, respectively. All the materials used except rosemary, which was not
      applied, were ovicidal to the eggs of H. tuberculatus. Despite the results of the
      in vitro assays, the in vivo treatments revealed that the pediculicidal activity
      was more pronounced with oils. All treated lice were killed after 0.5-2 min,
      whereas with d-phenothrin, 100% mortality was reached only after 120 min. The
      number of lice infesting buffaloes was significantly reduced 3, 6, 4, 6 and 9
      days after treatment with camphor, peppermint, chamomile, onion, and d
      phenothrin, respectively. Moreover, the oils and d-phenothrin significantly
      repelled flies, Musca domestica, Stomoxys calcitrans, Haematobia irritans and
      Hippobosca equina, for 6 and 3 days post-treatment, respectively. No adverse
      effects were noted on either animals or pour-on operators after exposure to the
      applied materials. Consequently, some Egyptian essential oils show potential for
      the development of new, speedy and safe lousicides and insect repellents for
      controlling lice and flies which infest water buffaloes.

PMID- 19596522
TI  - Kraepelin-Fraud syndrome: what's new?

PMID- 19596523
TI  - Application of biomimetic mineralization: a prophylactic therapy for cracked
      teeth?
AB  - Cracked teeth are usually found and easily ignored in clinic. If not found in
      time, they can lead to pulpitis and teeth fractures, which even can make the
      cracked teeth pulled out. The current treatments for cracked teeth include
      occlusal adjustments or preventive fillings, and the root canal therapy or
      complete crown restoration, which is decided according to the depth of cracks.
      However, the successful rate of preserving cracked teeth is less than 50% through
      occlusal adjustments and preventive fillings. Although the successful rate can
      reach 80% through the root canal therapy and complete crowns, the pulp and normal
      tooth can not be reserved. So the harms are very serious that prevention of its
      further development is extremely important. Nanobacteria have a very unique role
      in biological mineralization, which can produce crystalline apatites in the
      conditions of physiological calcium and phosphorus concentrations. Therefore, a
      hypothesis is put forward that application of nanobacteria may mineralize the
      cracks of teeth. Then the development of cracked teeth would be completely
      stopped.

PMID- 19596521
TI  - Estradiol and the relationship between dendritic spines, NR2B containing NMDA
      receptors, and the magnitude of long-term potentiation at hippocampal CA3-CA1
      synapses.
AB  - When circulating estrogen levels decline as a natural consequence of menopause
      and aging in women, there is an increased incidence of deficits in working
      memory. In many cases, these deficits are rescued by estrogen replacement
      therapy. These clinical data therefore highlight the importance of defining the
      biological pathways linking estrogen to the cellular substrates of learning and
      memory. It has been known for nearly two decades that estrogen enhances dendritic
      spine density on apical dendrites of CA1 pyramidal cells in hippocampus, a brain
      region required for learning. Interestingly, at synapses between CA3-CA1
      pyramidal cells, estrogen has also been shown to enhance synaptic NMDA receptor
      current and the magnitude of long-term potentiation, a cellular correlate of
      learning and memory. Given that synapse density, NMDAR function, and long-term
      potentiation at CA3-CA1 synapses in hippocampus are associated with normal
      learning, it is likely that modulation of these parameters by estrogen
      facilitates the improvement in learning observed in rats, primates and humans
      following estrogen replacement. To facilitate the design of clinical strategies
      to potentially prevent or reverse the age-related decline in learning and memory
      during menopause, the relationship between the estrogen-induced morphological and
      functional changes in hippocampus must be defined and the role these changes play
      in facilitating learning must be elucidated. The aim of this report is to provide
      a summary of the proposed mechanisms by which this hormone increases synaptic
      function and in doing so, it briefly addresses potential mechanisms contributing
      to the estrogen-induced increase in synaptic morphology and plasticity, as well
      as important future directions.

PMID- 19596524
TI  - Depression, another autoimmune disease from the view of autoantibodies.
AB  - Immune dysregulation is very common in major depression (MD) patients, with these
      individuals incurring increased risk for development of chronic inflammatory
      disease or autoimmune disease. Meanwhile, depressive symptoms have been found at
      a high prevalence in autoimmune disease. This apparent convergence suggests they
      may share a common pathogenic factor, or a close interaction innate. Recent
      studies have found that autoantibodies play an important role in the pathogenesis
      of depression both in animal models and human. Here, we suggest that depression,
      in nature, can be regarded as autoimmune disease caused by various
      autoantibodies, which broadens our understanding of depression, and brings about
      new fields for research and clinical implications of the disease.

PMID- 19596525
TI  - Epithelioid angiomatous nodule of head and neck.
AB  - Epithelioid vascular proliferations comprise a wide morphologic spectrum, ranging
      from reactive hyperplasia via benign tumor to malignant conditions. Epithelioid
      angiomatous nodule (EAN) is a recently recognized benign vascular proliferation
      with distinct clinical and pathological features. We review the literature and
      present six additional EANs in the head and neck examined by
      immunohistochemistry. This series comprised an equal number of males (n=3) and
      females (n=3) aged 13-45 years (mean 25.8 years). The sites of origin included
      the tongue (n=2), skin of the lip (n=2), periorbital and temporal skin (n=1), and
      nose (n=1). A painless solitary nodule (n=4) was the most common presentation.
      The lesions were distributed in the epidermis and subcutis, with a characteristic
      unilobular solid proliferation of polygonal epithelioid endothelial cells with
      intracytoplasmic primitive lumina. The distinction of EAN from other lesions of
      the heterogeneous group with epithelioid vascular proliferation can usually be
      made on the basis of the clinical and morphological features. This series
      indicates that the distribution of EAN in the head and neck region is not
      uncommon, which is in contrast to what was initially thought. EAN may be a
      variant of epithelioid hemangioma.

PMID- 19596526
TI  - Expression of xenobiotic and steroid hormone metabolizing enzymes in
      hepatocellular tumors of the non-cirrhotic liver.
AB  - Hepatocellular adenomas (HCA) and some hepatocellular carcinomas (HCC) arise in
      the non-cirrhotic liver. Although the liver is involved in the metabolism of a
      huge number of exogenous and endogenous substances, little is known about the
      role of metabolic enzymes in the development of liver tumors in the absence of
      cirrhosis. We analyzed the expression of glutathione S-transferases (GST) and
      cytochrome P450 enzymes (CYP) in 23 HCA, 20 HCC, and 22 focal nodular
      hyperplasias (FNH) using immunohistochemistry. The liver tissue revealed
      consistent specific staining for GST alpha, CYP1A1, 1A2, 2E1, and 3A4. In HCA and
      HCC, GST alpha expression was significantly reduced (p<0.001 and 0.043). Reduced
      GST alpha expression was significantly associated with steatosis in HCA and HCC
      (n=12, p=0.006), but not in non-neoplastic liver tissue. CYP3A4 expression was
      also reduced in HCA and HCC (p=0.03 and 0.02), and this was correlated with
      diabetes mellitus type 2 (p=0.02). In conclusion, HCA and HCC revealed changes in
      the expression of certain metabolic enzymes as compared with the non-neoplastic
      liver tissue or FNH. Therefore, reduced expression of GST alpha and CYP3A4 may
      indicate specific metabolic defects in the tumor tissue characterizing subgroups
      of HCA and HCC.

PMID- 19596528
TI  - Interspecies transmission of equine influenza virus (H3N8) to dogs by close
      contact with experimentally infected horses.
AB  - In horse populations, influenza A virus subtype H3N8 (equine influenza virus,
      EIV) is a very important pathogen that leads to acute respiratory disease.
      Recently, EIV has emerged in dogs, and has become widespread among the canine
      population in the United States. The interspecies transmission route had thus far
      remained unclear. Here, we tested whether the interspecies transmission of EIV to
      dogs could occur as a result of close contact with experimentally EIV-infected
      horses. Three pairs consisting of an EIV-infected horse and a healthy dog were
      kept together in individual stalls for 15 consecutive days. A subsequent
      hemagglutination inhibition test revealed that all three dogs exhibited
      seroconversion. Moreover, two of the three dogs exhibited virus shedding.
      However, the dogs exhibited no clinical signs throughout the course of the study.
      These data suggest that the interspecies transmission of EIV to dogs could occur
      as a result of close contact with EIV-infected horses without clinical symptoms.
      Although the interspecies transmission of EIV is unlikely to become an immediate
      threat to canine hygiene, close contact between EIV-infected horses and dogs
      should be avoided during an EI epidemic.

PMID- 19596527
TI  - Nicotine dependence and genetic variation in the nicotinic receptors.
AB  - Technological advances have led to the discovery of genetic variants that
      contribute to many illnesses including nicotine dependence. A multi-stage model
      of the development of nicotine dependence underlies these genetic studies, and it
      includes a progression through several stages of smoking behavior from never
      smoking to nicotine dependence. The final step in this model of dependence is the
      progression from established smoking behavior to the development of nicotine
      dependence. Contrasting individuals who smoke only a few cigarettes per day, or
      "chippers", to heavy smoking, nicotine dependent subjects, focuses a genetic
      study on the transition from smoking to nicotine dependence. This approach has
      identified distinct genetic variants that contribute to nicotine dependence on
      chromosome 15 in the region of the alpha5-alpha3-beta4 family of nicotinic
      receptor genes. This region of association includes an amino acid change in the
      alpha5 nicotinic receptor protein, which is most likely a biological variant
      altering the risk of developing dependence. There is also evidence that other
      variants alter alpha5 nicotinic receptor gene expression and potentially the risk
      of smoking. The discovery of these genetic variants and their contribution to the
      development of nicotine dependence highlight some of the many challenges in
      genetic studies. The first is that the prevalence of risk alleles can vary across
      populations so that a genetic risk factor can have a larger or small effect in a
      population depending on its frequency. The second challenge is that the risk that
      each genetic variant contributes in the development of a disorder is small and so
      it is many genes along with environmental risk factors that contribute to the
      development of a disorder. Interestingly, recent genetic studies of lung cancer
      and chronic obstructive pulmonary disease demonstrate that this same region has
      an important genetic influence on these disorders. Finally, there are differences
      in the risk of developing nicotine dependence based on gender and socioeconomic
      status. As our understanding of the genetic contributions of nicotine dependence
      increases, we may improve and personalize our treatments for smoking cessation
      and enhance our knowledge of other smoking related diseases in those who are at
      high risk for the many adverse consequences of smoking.

PMID- 19596529
TI  - Serotype distribution and production of muramidase-released protein,
      extracellular factor and suilysin by field strains of Streptococcus suis isolated
      in the United States.
AB  - Streptococcus suis is an important swine pathogen and a zoonotic agent.
      Differences in virulence have been noted among the 33 described serotypes,
      serotype 2 being considered the most virulent. In this study, we aimed at
      assessing the serotype distribution and the production of virulence-associated
      markers by strains recovered from diseased pigs in the United States (U.S.).
      Results showed that among the 100 strains evaluated, serotype 3 (20% of the
      isolates) and serotype 2 (17%) were the most prevalent. We then investigated the
      presence in these isolates of the genes sly, epf and mrp, encoding the virulence
      associated markers suilysin (SLY), extracellular factor (EF) and muramidase
      released (MRP) protein, respectively. The effective production of the markers by
      the strains was also verified. Results showed that the presence of the gene did
      not always correlate with actual expression of the respective protein. In the
      case of MRP, this was due, in most cases, to frameshift mutations at the 5' end
      of the gene resulting in premature stop codons. The most prevalent phenotypes
      among U.S. strains were MRP(+)EF(-)SLY(-) (40%) and MRP(-)EF(-)SLY(+) (35%).
      Serotype distribution greatly differed from that reported in several European
      countries, as did the production of virulence markers, particularly for serotype
      2. On the other hand, our results for the U.S. S. suis isolates are similar to
      those reported for Canadian strains, suggesting a common status in North America.

PMID- 19596530
TI  - Detection of fluoroquinolone resistance level in clinical canine and feline
      Escherichia coli pathogens using rapid real-time PCR assay.
AB  - Fluoroquinolones are used to treat infections caused by Escherichia coli in
      canine and feline veterinary patients, particularly those infecting the urinary
      tract. The gyrA gene is a primary target causing fluoroquinolone resistance in
      gram negative coliforms, with mutations in codons 83 and 87 generally associated
      with high-level of resistance E. coli clinical isolates. We have developed a
      fluorescence resonance energy transfer (FRET) quantitative PCR to identify
      enrofloxacin-resistance in clinical E. coli isolates that carry mutations in
      codons 83 and 87 of gyrA. This real-time quantitative PCR assay is rapid,
      economical, and sensitive compared with cultured antimicrobial susceptibility
      testing. The assay identified as few as four genome copies per reaction from
      culture and 19 genome copies in urine. For the 70 isolates tested, the
      sensitivity was 87.5% (95% CI=75-95.3%) (n=42/48), specificity was 100% (95%
      CI=87.3-100%) (n=22/22), whereas accuracy was 91.4% (95% CI=82.3-97%) (n=64/70).
      Furthermore, we were able to accurately differentiate between the wild type and
      mutants E. coli directly from infected canine urine samples (n=5) within 2 h.
      These results were confirmed by sequence alignments of the PCR products and
      comparison with the susceptibility testing. The FRET-PCR assay appears to have
      promising clinical application as an early diagnostic tool for rapid and
      sensitive detection and differentiation of the level of fluoroquinolone
      resistance among clinical E. coli isolates that may facilitate design of the
      dosing regimen.

PMID- 19596532
TI  - [Kytococcus schroeteri infectious endocarditis].

PMID- 19596531
TI  - [Female lung cancer trends, staging and histology in Herault, France].
AB  - BACKGROUND: In France, lung cancer is the third most common cancer and the third
      leading cause of cancer death in women. The main objective of this study is to
      analyse specificities of lung cancer in the female population in an
      administrative district in France, focusing on histology, staging and trends over
      time. METHODS: Incidence data from 1987 to 2004 were extracted from the Herault
      cancer registry. The variables of interest considered at diagnosis were stage,
      histology and age. Mortality data were extracted from the CepiDc-Inserm database
      for the same period. RESULTS: Among the 6,650 patients studied, 16.8% were women.
      18.3% of whom were aged less than 50 at diagnosis, (9.9% of men, p<0.001). Lung
      cancer incidence is increasing in the female population (+6.4% per year) as well
      as lung cancer mortality (+3.5% per year). This occurred faster for
      adenocarcinoma, young women and stages III-IV. CONCLUSION: This population-based
      study confirmed the specific features of lung cancer in women: younger age at
      diagnosis, adenocarcinoma and stage at diagnosis with poor prognosis. These
      results raise the question of possible differences to lung cancer susceptibility
      between males and females.

PMID- 19596533
TI  - Mandibular lingual vascular canals (MLVC): evaluation on dental CTs of a case
      series.
AB  - PURPOSE: The aim of this study was to assess the anatomy of the mandibular
      lingual foramen (MLF) and its linked canals (mandibular lingual vascular canals -
      MLVC), describing their frequency, diameter, location, and course. MATERIALS AND
      METHODS: One hundred and fourteen computed tomography (CT) images of the mandible
      (57 male and 57 female; mean age 44.70+/-12.53; age range 13-75 years, were
      evaluated. The CT sections were obtained on axial plane by using a bone
      reconstruction algorithm and then processed with dedicated software (Dentascan),
      with a standard protocol. RESULTS: 103 patients (90.35%) had at least one lingual
      vascular canal and 52 (45.61%) had multiple (two or three) canals. The typical
      locations of MLVC were the midline of the mandible (median lingual canal [MLC]).
      The mean diameter of the lingual canals in the midline (MLC) was 0.8mm+/-0. The
      direction of MLC progresses in an anterior and slightly caudal sense.
      CONCLUSIONS: Dental CT examination easily demonstrates the presence, position,
      direction and size of the lingual foramen and of the lingual vascular canals of
      the mandible. Radiologists and oral surgeons should be aware of these canals and
      their importance, in order to prevent bleeding complications during implants
      placement and other surgical procedures.

PMID- 19596534
TI  - Use of a quality-by-design approach to justify removal of the HPLC weight % assay
      from routine API stability testing protocols.
AB  - Due to the high method variability (typically > or = 0.5%, based on a literature
      survey and internal Merck experience) encountered in the HPLC weight percent (%)
      assays of various active pharmaceutical ingredients (APIs), it is proposed that
      the routine use of the test in stability studies should be discouraged on the
      basis that it is frequently not sufficiently precise to yield results that are
      stability-indicating. The high method variability of HPLC weight % methods is not
      consistent with the current ICH practice of reporting impurities/degradation
      products down to the 0.05% level, and it can lead to erroneous out-of
      specification (OOS) results that are due to experimental error and are not
      attributable to API degradation. For the vast majority of cases, the HPLC
      impurity profile provides much better (earlier and more sensitive) detection of
      low-level degradation products. Based on these observations, a Quality-by-Design
      (QbD) approach is proposed to phase out the HPLC weight % assay from routine API
      stability testing protocols.

PMID- 19596535
TI  - Characterization and quantification of phenolic compounds of extra-virgin olive
      oils with anticancer properties by a rapid and resolutive LC-ESI-TOF MS method.
AB  - The characterization and quantification of extra-virgin olive oil (EVOO) phenolic
      compounds by a rapid resolution liquid chromatography (RRLC) method coupled to
      diode-array and time of flight mass spectrometry (TOF) detection systems was
      developed. The RRLC method transferred from a conventional HPLC one achieved
      better performance with shorter analysis times. The phenolic compounds were
      separated with a C18 column (150 mm x 4.6mm, 1.8 microm) using water with 0.5%
      acetic acid and acetonitrile as mobile phases. Good peak resolution was obtained
      and 19 different phenols were identified in less than 20 min providing a new
      level of information about the samples in shorter time. The applicability of this
      analytical approach was confirmed by the successful analysis of three different
      EVOO varieties (Picual, Hojiblanca, and Arbequina) obtained from different
      trademarks. Besides identification of the most important phenolic compounds and
      their quantification in three different ways (RRLC-UV, RRLC-MS and a new approach
      using the total polyphenol content obtained with Folin Ciocalteau, the relative
      areas and the response factors), we also described the occurrence of correlations
      between the phenolic composition of EVOO-derived crude phenolic extracts and
      their anti-proliferative abilities toward human breast cancer-derived cell lines.
      When compared with lignans-rich EVOO varieties, secoiridoids-rich EVOO had a
      significantly strong ability to alter cell viability in four different types of
      human breast carcinoma cells.

PMID- 19596537
TI  - Ultraperformance liquid chromatography tandem mass spectrometric method for
      direct quantification of salbutamol in urine samples in doping control.
AB  - A fast and reliable quantitative method for salbutamol using direct analysis of
      the urine sample by ultraperformance liquid chromatography tandem mass
      spectrometry (UPLC/MS/MS) has been developed. Urine samples were spiked with
      salbutamol-d6 (internal standard), and, then, they were diluted with ultrapure
      water (1:1, v/v). Aliquots of 1 microl of the mixture were directly analyzed by
      UPLC/MS/MS. The chromatographic separation was performed in a UPLC BEH C18 (100
      mm x 2.1 mm, 1.7 microm) column with a mobile phase contained 0.01% formic acid
      in ultrapure water (v/v) and 0.01% formic acid in acetonitrile (v/v), using
      gradient elution at 0.6 ml/min. The temperature of the column was set to 45
      degrees C. The total run time was 3.2 min. Electrospray ionization in positive
      ion mode was used under multiple reaction monitoring (MRM) at different collision
      energies. Nitrogen and argon were used as desolvation and collision gas,
      respectively. The method was shown to be linear from 200 to 5000 ng/ml (r2>0.99).
      The limit of quantitation was estimated in 200 ng/ml. Intra-assay precision and
      accuracies, evaluated by using quality control samples containing 550 and 1100
      ng/ml salbutamol, were always better than 8.4%. The intermediate precision was
      estimated to be in the range of 5.6-8.9%. The method was shown to be reliable
      when applying to routine samples, and the short analysis time resulting from a
      simple sample preparation and a fast instrumental analysis makes it of great
      interest for antidoping control purposes.

PMID- 19596536
TI  - A protein-coated magnetic beads as a tool for the rapid drug-protein binding
      study.
AB  - A simple and fast method for the determination of the association constant (K(a))
      of ligand to human serum albumin (HSA) has been developed by using human serum
      albumin-coated magnetic beads (HSA-MB). To date, magnetic beads (MB) have been
      increasingly used as a bioseparation tool, especially for DNA, RNA, protein,
      enzyme and cell isolation or purification. In this study, HSA-MB were used as a
      new tool to determine the affinity of known ligands to HSA. The K(a) for l
      tryptofan, fenoprofen, ketoprofen, tolbutamide and warfarin obtained from
      Schathard analysis are consistent with previously reported values. The different
      K(a) values for ketoprofen after the acetylation of HSA-MB by preincubation with
      acetylosalicylic acid indicate that these beads can be successfully adapted in
      combined experiment. In addition, the HSA-MB experiment with phenytoin and
      valproic acid proved to be a simple method to examine drug displacement effect.

PMID- 19596538
TI  - Obstetrician-gynecologists' practices and perceived knowledge regarding
      immunization.
AB  - BACKGROUND: Obstetrician-gynecologists can play a key role in providing
      appropriate vaccinations to women of childbearing age. PURPOSE: This study
      investigated immunization knowledge and practices, and opinions concerning
      potential barriers to immunization, among obstetrician-gynecologists. METHODS: In
      2007, surveys were sent to Collaborative Ambulatory Research Network members, a
      representative sample of practicing Fellows of the American College of
      Obstetricians and Gynecologists; 394 responded (51.2%). Data analysis was
      completed in 2008. RESULTS: Most responding obstetrician-gynecologists disagreed
      that "routine screening for vaccine-preventable diseases falls outside of the
      routine practice of an ob/gyn." A majority (78.7%) stock and administer at least
      some vaccines. Among those who stock vaccines, 91.0% stock the human
      papillomavirus vaccine, and 66.8% stock the influenza vaccine. All other vaccines
      were stocked by <30% of practices that stock vaccines. A majority of physicians
      agreed that financial factors (e.g., inadequate reimbursement) were barriers to
      vaccine administration. Most were aware that the influenza (89.8%); hepatitis B
      (64.0%); and tetanus, diptheria, pertussis (58.6%) vaccines are safe to
      administer during pregnancy, and that the measles, mumps, rubella (97.5%); and
      varicella (92.9%) vaccines are not. Most (84.5%) were in concordance with
      recommendations that all pregnant women should receive the influenza vaccine. A
      majority believed their immunization training was less than adequate and believed
      their practice would benefit from continuing medical education courses.
      CONCLUSIONS: Immunization is an important part of women's health care and has
      been, at least partially, incorporated into obstetrician-gynecologist practice.
      Financial burdens and knowledge regarding vaccine recommendations remain barriers
      to vaccine administration. Additional training and professional information may
      benefit obstetric-gynecologic practice.

PMID- 19596539
TI  - [Optimization of anesthesia for emergency abdominal surgery in the elderly].
AB  - OBJECTIVES: Peroperative haemodynamic profile comparison of two anaesthetic
      protocols for emergency abdominal surgery of old patients. PATIENTS AND METHODS:
      Non-randomized monocentric study. Patients in the Optimization group were
      prospectively studied. Anaesthesia was induced by etomidate-succinylcholine and
      maintained with effect site and end-tidal target controlled administration of
      remifentanil and desflurane respectively to keep the BIS values between 45 and
      55. These patients were matched with retrospectively studied patients
      constituting the Control group. The latter's were anaesthetized with etomidate
      succinylcholine and anaesthesia was maintained by manually controlled
      administration of sufentanil and desflurane to keep systolic arterial pressure
      (SAP) within a range of more or less 30% of preoperative baseline SAP. RESULTS:
      Twelve patients (86+/-5 yrs) were included in the Optimization group, 11 (86+/-4
      yrs) in the Control group. The time spent at a SAP within more or less 30% of
      baseline values was 92+/-7% and 71+/-29% of total anesthesia time in the
      Optimization and Control groups respectively (p<0.05). That spent at a SAP less
      than 15 and 30% of baseline values was 23+/-11% et 3+/-5% of total anaesthesia
      time in the Optimization group, whereas in the MAN group it was 65+/-21% and 27+/
      30% respectively (p<0.05). Desflurane and ephedrine consumption was less in the
      Optimization group as well as crystalloid or colloid volume loading. CONCLUSION:
      Anaesthetic agents target controlled administration and/or neurophysiologic depth
      of anaesthesia monitoring improve the time course of the haemodynamic effects in
      elderly patients undergoing abdominal surgery in emergency.

PMID- 19596540
TI  - [Principles of mechanical ventilation weaning in paediatric intensive care].

PMID- 19596541
TI  - [TV addiction with skin manifestations: a new syndrome "TV addict bursitis"].

PMID- 19596542
TI  - Arthroscopy for labral tears in patients with developmental dysplasia of the hip:
      a cautionary note.
AB  - Patients with developmental dysplasia of the hip may present with acetabular rim
      overloading, labral hypertrophy, and tear. Our hypothesis was that isolated
      arthroscopic treatment of labral tear is likely to fail in most patients. We
      investigated 34 patients who underwent at least one arthroscopy of the hip for
      labral tear. Developmental hip dysplasia or other morphologic abnormalities of
      the hip were confirmed in all patients. Arthroscopy failed to relieve pain in 24
      patients. We observed accelerated arthritis in 14 patients and migration of the
      femoral head in 13 patients. Sixteen patients underwent further surgery (further
      surgeries included periacetabular osteotomy [6 patients], femoroacetabular
      osteoplasty [7 patients], and total hip arthroplasty [3 patients]). At the latest
      follow-up, all patients but one were pain-free. Patients with evidence of
      abnormal hip morphologies may not benefit from hip arthroscopy and isolated
      treatment of the labrum; in fact, the latter may accelerate the process of
      arthritis in some patients.

PMID- 19596543
TI  - Labral disease associated with femoroacetabular impingement: do we need to
      correct the structural deformity?
AB  - In this study, we compared the clinical results of arthroscopic partial labral
      resection to augmentation of this procedure with limited open osteochondroplasty
      for the treatment of symptomatic femoroacetabular impingement. Two consecutive
      cohorts were evaluated: (a) group I, arthroscopic treatment of labrum and
      articular cartilage, and (b) group II, hip arthroscopy augmented with limited
      osteochondroplasty of the femoral head-neck junction. Group I (23 hips) and group
      II (25 hips) patients had no difference in age, labral disease patterns,
      osteoarthritis grade, or chondromalacia. Mean follow-up was slightly longer in
      group I. The modified Harris Hip Score showed a trend toward higher values in
      group II. A 10-point improvement was more common in group II, and fewer group II
      patients required subsequent surgery. These preliminary data suggest that
      patients with cam femoroacetabular impingement may have improved clinical
      outcomes when the impingement deformity is corrected.

PMID- 19596544
TI  - Long-term results of a contemporary metal-on-metal total hip arthroplasty: a 10
      year follow-up study.
AB  - The goal of the study was to evaluate the long-term results of a metal-on-metal
      articulation. We evaluated the results and histologic findings in patients who
      had undergone revision. One hundred total hip arthroplasties with a Lubrimet
      metal-on-metal articulation (Smith and Nephew, Rotkreuz, Switzerland) were
      implanted in 99 consecutive unselected patients in 1995 and 1996, and the results
      were prospectively analyzed up to a mean of 126 months postoperatively.
      Periprosthetic tissues of all 6 hips that had undergone revision because of
      aseptic loosening, mechanical failure, or periprosthetic fracture showed
      metallosis and extensive lymphocytic and plasma cell infiltration around the
      metal debris. With removal of the component because of aseptic loosening as the
      end point, survivorship was 98% for the stem and 96% for the cup.

PMID- 19596545
TI  - The correlates and consequences of early appearing social anxiety in young
      children.
AB  - Social anxiety is the fear of social situations and being negatively evaluated by
      others. Most previous studies of childhood social anxiety have employed clinical
      samples of children aged 10 years and older. The current study explored the
      correlates of social anxiety in an unselected sample of young children.
      Participants were n=178 elementary school children in grade 2 (aged 7-8 years).
      Children were individually administered the Social Anxiety Scale for Children
      Revised (SASC-R), as well as measures of socio-emotional adjustment. Teachers
      completed measures of children's socio-emotional problems and school adjustment.
      Results indicated that social anxiety was positively associated with self
      reported loneliness, school avoidance, and internalizing coping, and negatively
      related to school liking. However, social anxiety was mostly unrelated to teacher
      rated outcomes. Findings are discussed in terms of use of the SASC-R for this
      type of population and reasons for the disparity between child and teacher
      reports of adjustment outcomes.

PMID- 19596546
TI  - Predictive learning with structured (grouped) data.
AB  - Many applications of machine learning involve sparse and heterogeneous data. For
      example, estimation of diagnostic models using patients' data from clinical
      studies requires effective integration of genetic, clinical and demographic data.
      Typically all heterogeneous inputs are properly encoded and mapped onto a single
      feature vector, used for estimating a classifier. This approach, known as
      standard inductive learning, is used in most application studies. Recently,
      several new learning methodologies have emerged. For instance, when training data
      can be naturally separated into several groups (or structured), we can view model
      estimation for each group as a separate task, leading to a Multi-Task Learning
      framework. Similarly, a setting where the training data are structured, but the
      objective is to estimate a single predictive model (for all groups), leads to the
      Learning with Structured Data and SVM+ methodology recently proposed by Vapnik
      [(2006). Empirical inference science afterword of 2006. Springer]. This paper
      describes a biomedical application of these new data modeling approaches for
      modeling heterogeneous data using several medical data sets. The characteristics
      of group variables are analyzed. Our comparisons demonstrate the advantages and
      limitations of these new approaches, relative to standard inductive SVM
      classifiers.

PMID- 19596547
TI  - RMP model based optimization of power system stabilizers in multi-machine power
      system.
AB  - This paper describes the nonlinear parameter optimization of power system
      stabilizer (PSS) by using the reduced multivariate polynomial (RMP) algorithm
      with the one-shot property. The RMP model estimates the second-order partial
      derivatives of the Hessian matrix after identifying the trajectory sensitivities,
      which can be computed from the hybrid system modeling with a set of differential
      algebraic-impulsive-switched (DAIS) structure for a power system. Then, any
      nonlinear controller in the power system can be optimized by achieving a desired
      performance measure, mathematically represented by an objective function (OF). In
      this paper, the output saturation limiter of the PSS, which is used to improve
      low-frequency oscillation damping performance during a large disturbance, is
      optimally tuned exploiting the Hessian estimated by the RMP model. Its
      performances are evaluated with several case studies on both single-machine
      infinite bus (SMIB) and multi-machine power system (MMPS) by time-domain
      simulation. In particular, all nonlinear parameters of multiple PSSs on IEEE
      benchmark two-area four-machine power system are optimized to be robust against
      various disturbances by using the weighted sum of the OFs.

PMID- 19596548
TI  - A hybrid random field model for scalable statistical learning.
AB  - This paper introduces hybrid random fields, which are a class of probabilistic
      graphical models aimed at allowing for efficient structure learning in high
      dimensional domains. Hybrid random fields, along with the learning algorithm we
      develop for them, are especially useful as a pseudo-likelihood estimation
      technique (rather than a technique for estimating strict joint probability
      distributions). In order to assess the generality of the proposed model, we prove
      that the class of pseudo-likelihood distributions representable by hybrid random
      fields strictly includes the class of joint probability distributions
      representable by Bayesian networks. Once we establish this result, we develop a
      scalable algorithm for learning the structure of hybrid random fields, which we
      call 'Markov Blanket Merging'. On the one hand, we characterize some complexity
      properties of Markov Blanket Merging both from a theoretical and from the
      experimental point of view, using a series of synthetic benchmarks. On the other
      hand, we evaluate the accuracy of hybrid random fields (as learned via Markov
      Blanket Merging) by comparing them to various alternative statistical models in a
      number of pattern classification and link-prediction applications. As the results
      show, learning hybrid random fields by the Markov Blanket Merging algorithm not
      only reduces significantly the computational cost of structure learning with
      respect to several considered alternatives, but it also leads to models that are
      highly accurate as compared to the alternative ones.

PMID- 19596549
TI  - Cross-situational learning of object-word mapping using Neural Modeling Fields.
AB  - The issue of how children learn the meaning of words is fundamental to
      developmental psychology. The recent attempts to develop or evolve efficient
      communication protocols among interacting robots or virtual agents have brought
      that issue to a central place in more applied research fields, such as
      computational linguistics and neural networks, as well. An attractive approach to
      learning an object-word mapping is the so-called cross-situational learning. This
      learning scenario is based on the intuitive notion that a learner can determine
      the meaning of a word by finding something in common across all observed uses of
      that word. Here we show how the deterministic Neural Modeling Fields (NMF)
      categorization mechanism can be used by the learner as an efficient algorithm to
      infer the correct object-word mapping. To achieve that we first reduce the
      original on-line learning problem to a batch learning problem where the inputs to
      the NMF mechanism are all possible object-word associations that could be
      inferred from the cross-situational learning scenario. Since many of those
      associations are incorrect, they are considered as clutter or noise and discarded
      automatically by a clutter detector model included in our NMF implementation.
      With these two key ingredients--batch learning and clutter detection--the NMF
      mechanism was capable to infer perfectly the correct object-word mapping.

PMID- 19596550
TI  - Local coupled feedforward neural network.
AB  - In this paper, the local coupled feedforward neural network is presented. Its
      connection structure is same as that of Multilayer Perceptron with one hidden
      layer. In the local coupled feedforward neural network, each hidden node is
      assigned an address in an input space, and each input activates only the hidden
      nodes near it. For each input, only the activated hidden nodes take part in
      forward and backward propagation processes. Theoretical analysis and simulation
      results show that this neural network owns the "universal approximation" property
      and can solve the learning problem of feedforward neural networks. In addition,
      its characteristic of local coupling makes knowledge accumulation possible.

PMID- 19596551
TI  - Optimal control of unknown affine nonlinear discrete-time systems using offline
      trained neural networks with proof of convergence.
AB  - The optimal control of linear systems accompanied by quadratic cost functions can
      be achieved by solving the well-known Riccati equation. However, the optimal
      control of nonlinear discrete-time systems is a much more challenging task that
      often requires solving the nonlinear Hamilton-Jacobi-Bellman (HJB) equation. In
      the recent literature, discrete-time approximate dynamic programming (ADP)
      techniques have been widely used to determine the optimal or near optimal control
      policies for affine nonlinear discrete-time systems. However, an inherent
      assumption of ADP requires the value of the controlled system one step ahead and
      at least partial knowledge of the system dynamics to be known. In this work, the
      need of the partial knowledge of the nonlinear system dynamics is relaxed in the
      development of a novel approach to ADP using a two part process: online system
      identification and offline optimal control training. First, in the system
      identification process, a neural network (NN) is tuned online using novel tuning
      laws to learn the complete plant dynamics so that a local asymptotic stability of
      the identification error can be shown. Then, using only the learned NN system
      model, offline ADP is attempted resulting in a novel optimal control law. The
      proposed scheme does not require explicit knowledge of the system dynamics as
      only the learned NN model is needed. The proof of convergence is demonstrated.
      Simulation results verify theoretical conjecture.

PMID- 19596552
TI  - Cellular Nonlinear Networks for the emergence of perceptual states: application
      to robot navigation control.
AB  - In this paper a new general purpose perceptual control architecture, based on
      nonlinear neural lattices, is presented and applied to solve robot navigation
      tasks. Insects show the ability to react to certain stimuli with simple reflexes,
      using direct sensory-motor pathways, which can be considered as basic behaviors,
      inherited and pre-wired. Relevant brain centres, known as Mushroom Bodies (MB)
      and Central Complex (CX) were recently identified in insects: though their
      functional details are not yet fully understood, it is known that they provide
      secondary pathways allowing the emergence of cognitive behaviors. These are
      gained through the coordination of the basic abilities to satisfy the insect's
      needs. Taking inspiration from this evidence, our architecture modulates, through
      a reinforcement learning, a set of competitive and concurrent basic behaviors in
      order to accomplish the task assigned through a reward function. The core of the
      architecture is constituted by the so-called Representation layer, used to create
      a concise picture of the current environment situation, fusing together different
      stimuli for the emergence of perceptual states. These perceptual states are
      steady state solutions of lattices of Reaction-Diffusion Cellular Nonlinear
      Networks (RD-CNN), designed to show Turing patterns. The exploitation of the
      dynamics of the multiple equilibria of the network is emphasized through the
      adaptive shaping of the basins of attraction for each emerged pattern. New
      experimental campaigns on standard robotic platforms are reported to demonstrate
      the potentiality and the effectiveness of the approach.

PMID- 19596553
TI  - An improved graph cut segmentation method for cervical lymph nodes on sonograms
      and its relationship with node's shape assessment.
AB  - A modified graph cut was proposed under the elliptical shape constraint to
      segment cervical lymph nodes on sonograms, and its effect on the measurement of
      short axis to long axis ratio (S/L) was investigated by using the relative
      ultimate measurement accuracy (RUMA). Under the same user inputs, the proposed
      algorithm successfully segmented all 60 sonograms tested, while the traditional
      graph cut failed. The mean RUMA resulted from the developed method was comparable
      to that resulted from the manual segmentation. Results indicated that utilizing
      the elliptical shape prior could appreciably improve the graph cut for nodes
      segmentation, and the proposed method satisfied the accuracy requirement of S/L
      measurement.

PMID- 19596554
TI  - Parental craniofacial cephalometric features of Chinese patients with
      nonsyndromic isolated cleft palate.
AB  - To evaluate the parental craniofacial morphology in Chinese patients with
      sporadic nonsyndromic cleft palate, 175 parental pairs of children with
      nonsyndromic cleft palate (NSCP) and 206 controls from Sichuan University were
      involved in this study. Conventional cephalometric analysis was used to measure
      angles, linear distances and their ratios. Two-sample Student's t-tests and
      multivariate discriminant analysis were applied to the data. The data indicated
      that fathers of children with NSCP tended to have longer anterior cranial base
      length, palatal length, mandibular body length, mandibular ramus length, and
      longer mandibular height, lower face height, as well as larger nasal width,
      palatal width, mandibular body width, and condyle distance (p<0.05). Mothers of
      children with NSCP tended to have longer mandibular body length, mandibular ramus
      length, and longer mandibular height, lower face height, as well as larger nasal
      width, palatal width, mandibular body width, and condyle distance (p<0.05). The
      results indicated that the healthy parents of the patients with NSCP show
      distinct characteristics in craniofacial morphology. In general, the
      characteristics seem to be more distinct in the fathers of cleft patients than in
      the mothers.

PMID- 19596555
TI  - Virtual model surgery and wafer fabrication for orthognathic surgery.
AB  - Model surgery is one of the most important steps in the preoperative workup for
      orthognathic surgery. In cases of complicated two-jaw surgery, manual model
      surgery requires many laboratory based steps that are time-consuming and may
      contain potential errors. Recently, a three-dimensional virtual model surgery (3D
      VMS) program (3Txer version 2, Orapix, Seoul, Korea) was introduced. The purpose
      of this article is to present a 3D-VMS case using combined data from 3D computed
      tomography and 3D virtual dental casts.

PMID- 19596556
TI  - The supernumerary nasal tooth.
AB  - Teeth exceeding the normal dental complement that have erupted into the nasal
      cavity are a rare pathological entity. This case report describes a female
      patient with recurrent complaints and fetid discharge from the left nasal cavity.
      The suspected clinical diagnosis of a supernumerary nasal tooth was confirmed by
      computed tomography. After endoscopic removal, the tooth was examined using X-ray
      microtomography and thin-section preparations; these findings are presented for
      the first time. A literature search identified 25 supernumerary nasal teeth in 23
      patients.

PMID- 19596558
TI  - Extension of normal values on sensory function for facial areas using clinical
      tests on touch and two-point discrimination.
AB  - The threshold value of a sensory test provides a numerical measure of the sensory
      function. In order to decide whether a threshold value from an affected site
      indicates 'abnormal' sensory function, it can be compared with normal values from
      a healthy control population. The aim of this study was to extend current
      information on normal values for static light touch and static two-point
      discrimination for facial sites. Using simple hand-held devices, 95% upper limits
      of confidence intervals of threshold values were determined for facial sites
      other than those studied previously and for a large sample of 100 healthy
      subjects. The MacKinnon-Dellon Disk-Criminator and the Aesthesiometer were used
      to measure novel normal values of two-point discrimination. As threshold values
      for two-point discrimination from the Aesthesiometer were similar to those
      obtained using the Disk-Criminator, the use of the Aesthesiometer might not be
      indicated. Apart from the Pressure Specified Sensory Device (a device with
      pressure control), Semmes-Weinstein nylon monofilaments and the Disk-Criminator
      are useful devices for studying sensory function, in particular under clinical
      test conditions in which easy and fast application are advantageous.

PMID- 19596557
TI  - Impact of treatment on quality of life for oral and oropharyngeal carcinoma.
AB  - This study evaluates the changes in quality of life (QoL) from pre-treatment to 3
      years after commencement of treatment and its relation to therapeutic variables
      in patients with oral and oropharyngeal carcinoma. QoL was assessed using the
      EORTC QLQ-C30 questionnaires and the EORTC head and neck cancer specific module
      QLQ-H&N35. QoL data were obtained prior to treatment and 1 and 3 years after
      treatment began. Of 128 patients, 69 completed all the questionnaires over the
      course of 3 years. Variable deterioration of QoL scores was detected before
      treatment. Most of the parameters worsened significantly after treatment and
      during the first year, and improved by the third year. Patients who underwent
      surgical treatment combined with adjuvant radiotherapy and chemotherapy generally
      showed worse scores and needed a long time to recover from the disease and the
      treatment adverse effects. This long-term prospective study performed using the
      EORCT questionnaires in a homogeneous group of patients with oral and
      oropharyngeal carcinoma may allow better understanding of the impact of treatment
      and the changes in QoL that occur.

PMID- 19596559
TI  - Isobolographic characterization of interactions of levetiracetam with the various
      antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.
AB  - The aim of this study was to characterize the anticonvulsant effects of
      levetiracetam (LEV) in combination with the various antiepileptic drugs
      (clonazepam [CZP], oxcarbazepine [OXC], phenobarbital [PB], tiagabine [TGB], and
      valproate [VPA]), in the mouse 6 Hz psychomotor seizure model. Limbic
      (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32
      mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes and
      isobolographic analysis for parallel and non-parallel dose-response effects was
      used to characterize the consequent anticonvulsant interactions between the
      various drug combinations. Potential concurrent adverse-effect profiles of
      interactions between LEV and CZP, OXC, PB, TGB, and VPA at the fixed-ratio of 1:1
      were evaluated in the chimney (motor performance), passive avoidance (long-term
      memory), and grip-strength (muscular strength) tests. LEV administered singly was
      associated with a dose-response relationship curve (DRRC) that was parallel to
      that for CZP and non-parallel to that for OXC, PB, TGB and VPA. With
      isobolography for parallel DRRCs, the combination of LEV with CZP at three fixed
      ratios of 1:3, 1:1 and 3:1 was additive in nature. With isobolography for non
      parallel DRRCs the combinations of LEV with OXC, TGB and VPA at the fixed-ratio
      of 1:1 were also additive. In contrast, the isobolography for non-parallel DRRCs
      revealed that the interaction for the combination of LEV with PB at the fixed
      ratio of 1:1 was supra-additive (synergistic). None of the combinations were
      associated with any concurrent adverse effects with regards to motor
      coordination, long-term memory or muscular strength. LEV is associated with
      favorable anticonvulsant synergism with PB and is additive with regards to CZP,
      OXC, TGB and VPA in the mouse 6 Hz psychomotor seizure model.

PMID- 19596560
TI  - Family-based association study of SELENBP1 in schizophrenia.
AB  - The SELENBP1 gene previously was found to be up-regulated in microarray analysis
      of both peripheral blood cell and brain tissue samples from schizophrenia
      patients. Quantitative PCR analysis subsequently corroborated the altered
      expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley
      Array Correction. The aim of this study was to extend those findings by employing
      family-based association methods to a sample of over 2400 individuals (including
      1214 individuals affected by schizophrenia) of Han Chinese descent living in
      Taiwan. One of four haplotype-tagging SNPs and two different two-marker
      haplotypes showed nominally significant evidence for association with
      schizophrenia under an additive model, suggesting that genetic variation in
      SELENBP1 may influence risk for the disorder, while this significance did not
      remain when other inheritance models were considered. Further comprehensive
      analysis with other SNPs and haplotypes is needed and warranted.

PMID- 19596561
TI  - High imipenem blood concentrations associated with toxic encephalopathy in a
      patient with mild renal dysfunction.

PMID- 19596562
TI  - Structural changes of piezoelectric La3Ga5SiO14 induced by paramagnetic ions
      revealed by 71Ga multiple quantum magic angle spinning.
AB  - Experimental evidence that nuclear magnetic resonance (NMR) can detect structural
      changes of piezoelectric La(3)Ga(5)SiO(14) induced by dilute paramagnetic ions is
      presented. Gd(3+) and Eu(3+) cations have been incorporated into
      La(3)Ga(5)SiO(14) monocrystals. As expected, the line-width of the tetrahedral
      (29)Si magic angle spinning (MAS) NMR spectra as well as the inverse of the T(2)
      relaxation time of (71)Ga increases with the concentration of the paramagnetic
      ions. A surprising result is shown by (71)Ga multiple quantum (MQ) MAS NMR
      spectrum, which changes with the concentration of paramagnetic ions. The changes
      in the (71)Ga MQMAS spectra can be explained by a more ordonated distribution of
      Ga ions inside the oxygen tetrahedra. The (71)Ga MQMAS NMR spectra allow
      identification of the one octahedral and two tetrahedral Ga sites.

PMID- 19596563
TI  - Methacholine challenge--comparison of an ATS protocol to a new rapid single
      concentration technique.
AB  - Bronchial methacholine challenge is well established in asthma diagnostics and
      research. ATS guidelines propose a five step standard dosimeter (SDM) protocol
      with incremental concentrations of methacholine to calculate the concentration
      causing a 20% drop in FEV(1) in an individual (PC(20)FEV(1)). In contrast, the
      aerosol provocation system (APS) by Viasys automatically determines the
      administered dose of methacholine by measuring the effective nebulisation time
      and referring it to drug concentration and nebuliser power. Therefore, it offers
      a feasible and less time-consuming provocation procedure by applying incremental
      doses (PD(20)) of methacholine using a single concentration (16mg/mL
      methacholine, APS-SC). In this study we compared these two methods in 52 young
      adults (25+/-5.8 years). Following a screening visit, subjects were randomly
      assigned to undergo either SDM or APS-SC followed by the other method within 1
      week. A close correlation between concentration and dosage causing a 20% fall of
      FEV(1) was found (r=0.69, p<0.001). Using the ATS categorisation of bronchial
      responsiveness we interpreted the results of the APS-SC method as follows: PD(20)
      methacholine<0.3mg as "moderate to severe BHR", 0.3 - 0.6mg as "mild BHR", 0.6 -
      1.0mg as "borderline BHR", and>1.0mg as "normal bronchial response". We conclude
      that the five-step APS-SC is a suitable method, providing reliable results. In
      clinical practice the APS-SC is a timesaving procedure and less prone to errors
      since only one dilution of methacholine is necessary compared to the SDM.

PMID- 19596566
TI  - FERM proteins in animal morphogenesis.
AB  - Proteins containing a FERM domain are ubiquitous components of the cytocortex of
      animal cells where they are engaged in structural, transport, and signaling
      functions. Recent years have seen a wealth of genetic studies in model organisms
      that explore FERM protein function in development and tissue organization. In
      addition, mutations in several FERM protein-encoding genes have been associated
      with human diseases. This review will provide a brief overview of the FERM domain
      structure and the FERM protein superfamily and then discuss recent advances in
      our understanding of the mechanism of function and developmental requirement of
      several FERM proteins including Moesin, Myosin-VIIA, Myosin-XV, Coracle/Band4.1
      as well as Yurt and its vertebrate homologs Mosaic Eyes and EPB41L5/YMO1/Limulus.

PMID- 19596565
TI  - A novel far-red bimolecular fluorescence complementation system that allows for
      efficient visualization of protein interactions under physiological conditions.
AB  - Fluorescent protein (FP) has enabled the analysis of biomolecular interactions in
      living cells, and bimolecular fluorescence complementation (BiFC) represents one
      of the newly developed imaging technologies to directly visualize protein-protein
      interactions in living cells. Although 10 different FPs that cover a broad range
      of spectra have been demonstrated to support BiFC, only Cerulean (cyan FP
      variant), Citrine and Venus (yellow FP variants)-based BiFC systems can be used
      under 37 degrees C physiological temperature. The sensitivity of two mRFP-based
      red BiFC systems to higher temperatures (i.e., 37 degrees C) limits their
      applications in most mammalian cell-based studies. Here we report that mLumin, a
      newly isolated far-red fluorescent protein variant of mKate with an emission
      maximum of 621 nm, enables BiFC analysis of protein-protein interactions at 37
      degrees C in living mammalian cells. Furthermore, the combination of mLumin with
      Cerulean- and Venus-based BiFC systems allows for simultaneous visualization of
      three pairs of protein-protein interactions in the same cell. The mLumin-based
      BiFC system will facilitate simultaneous visualization of multiple protein
      protein interactions in living cells and offer the potential to visualize protein
      protein interactions in living animals.

PMID- 19596567
TI  - Temporal dynamics of patterning by morphogen gradients.
AB  - Morphogens act as graded positional cues to control cell fate specification in
      many developing tissues. This concept, in which a signaling gradient regulates
      differential gene expression in a concentration-dependent manner, has received
      considerable experimental support. Nevertheless, several recent studies have
      challenged the straightforward model of morphogen activity. In particular, the
      observation that pattern formation is a dynamic process has raised questions
      about the influence of time on morphogen activity. Here we propose that the
      spatiotemporal dynamics of the cellular response to a morphogen gradient depend
      on a combination of temporal alterations to the morphogen gradient itself, the
      dynamics of its signal transduction and downstream interactions between target
      genes.

PMID- 19596568
TI  - Diagnostic and therapeutic strategies for minimally and widely invasive
      follicular thyroid carcinomas.
AB  - The purpose of this study is to investigate diagnostic and therapeutic strategies
      that will enable easy differentiation between minimally invasive follicular
      carcinoma (MIFC) and widely invasive follicular carcinoma (WIFC). We
      retrospectively reviewed 234 follicular thyroid carcinoma cases to compare the
      diagnostic and therapeutic characteristics between the minimally and the widely
      invasive types. Eighty-nine patients were diagnosed with MIFC (mean age, 39.2 +/
      14.9 years) and 145 were diagnosed with WIFC (mean age, 49.0 +/- 17.7 years). Low
      diagnostic accuracy from preoperative cytology and frozen sections resulted in 60
      patients undergoing subtotal thyroidectomies and 57 cases required a second
      operation for complete thyroidectomy. Patients in the MIFC group were younger,
      and had small-sized tumors, lower postoperative thyroglobulin levels, lower
      recurrent rates and lower cancer mortality rates than those in the WIFC group.
      Diagnostic accuracy from frozen sections in the WIFC group was relatively better.
      After a mean follow-up period of 9.0+/-0.4 years, 41 of the 234 (17.5%) patients
      with follicular thyroid carcinoma had died due to thyroid cancer. All MIFC
      patients remained disease-free or had a recurrence-free status. In conclusion,
      both WIFC and MIFC are difficult to diagnose on the basis of preoperative
      examinations and frozen sections. Patients diagnosed with MIFC had responded
      positively to the treatment; however, for patients diagnosed with WIFC to become
      disease-free, early diagnosis and aggressive surgical therapies in combination
      with (131)I therapy were required.

PMID- 19596569
TI  - Prediction of membrane fouling in MBR systems using empirically estimated
      specific cake resistance.
AB  - The focus of this study was to empirically estimate the specific cake resistance
      (SCR) by the variation in shear intensity (G) in four laboratory-scale MBRs. The
      control reactor (MBR(0)) was operated with aeration only while other MBRs
      (MBR(150), MBR(300) and MBR(450)) were operated with aeration and mechanical
      mixing intensities of 150, 300 and 450 rpm, respectively. It was found that the
      SCR was strongly correlated (R(2)=0.99) with the fouling rates in the MBRs.
      Moreover, the contribution of cake resistance (R(c)) to the total hydraulic
      resistance (R(t)) was predominant compared to the irreversible fouling resistance
      (R(f)). On this basis, the cake filtration model was selected as a predictive
      tool for membrane fouling. This model was modified by replacing the SCR with its
      empirical shear intensity relationship. The modified model can predict the
      fouling rate for a given shear intensity (G) within 80 and 250 s(-1) in a MBR
      system.

PMID- 19596570
TI  - Carbon source recovery from waste activated sludge by alkaline hydrolysis and
      gamma-ray irradiation for biological denitrification.
AB  - The recovery of an organic carbon source from a waste activated sludge by using
      alkaline hydrolysis and radiation treatment was studied, and the feasibility of
      the solubilized sludge carbon source for a biological denitrification was also
      investigated. The effects of an alkaline treatment and gamma-ray irradiation on a
      biodegradability enhancement of the sludge were also studied. A modified
      continuous bioreactor for a denitrification (MLE reactor) was operated by using a
      synthetic wastewater for 47 days. Alkaline treatment of pH 10 and gamma-ray
      irradiation of 20 kGy were found to be the optimum carbon source recovery
      conditions. COD removal of 84% and T-N removal of 51% could be obtained by using
      the solubilized sludge carbon source through the MLE denitrification process. It
      can be concluded that the carbon source recovered from the waste activated sludge
      was successfully employed as an alternative carbon source for a biological
      denitrification.

PMID- 19596571
TI  - Mathematical representation of xanthine oxidase activity in hydro-organic
      mixtures.
AB  - A mathematical model is proposed to calculate the enzyme activity in different
      concentrations of the organic solvent in hydro-organic mixtures. The accuracy and
      predictability of the model have been evaluated employing experimentally
      determined xanthine oxidase activity in five hydro-organic mixtures by using
      absolute percentage mean deviation (APMD). The obtained APMD for correlative and
      predictive studies were 5.3% and 7.6%, respectively.

PMID- 19596572
TI  - Impact of substrates acclimation strategy on simultaneous biodegradation of
      hydrogen sulfide and ammonia.
AB  - Three columns were differentiated with feeding mixture of H(2)S and NH(3) (MFC),
      feeding NH(3) followed by H(2)S (NFC), and feeding H(2)S followed by NH(3) (SFC).
      Removal performance, biodegradation capacity and microbial community structures
      in the three columns were compared. The results show that NFC has a shorter
      acclimation period for the removal of NH(3) gas and nitrification than MFC. Under
      the high loading of H(2)S and NH(3) at 164 and 82 gm(-3) h(-1), respectively, NFC
      exhibited high removal efficiency of NH(3) (>95%) while the removal efficiencies
      were obtained at 63 and 75% in MFC and SFC, respectively. The removal of NH(3)
      gas in NFC was significantly attributed to nitrification (over 50%), while
      adsorption and chemical reaction contributed to the removal of NH(3) in MFC and
      SFC. The different biodegradation capacities of NH(3) could be due to the
      dissimilarity in the microbial population presented in each column.

PMID- 19596573
TI  - Ulmosides A and B: flavonoid 6-C-glycosides from Ulmus wallichiana, stimulating
      osteoblast differentiation assessed by alkaline phosphatase.
AB  - Chemical investigation of Ulmus wallichiana stem bark resulted in isolation and
      identification of three new compounds (2S,3S)-(+)-3',4',5,7
      tetrahydroxydihydroflavonol-6-C-beta-D-glucopyranoside (1), (2S,3S)-(+)-4',5,7
      trihydroxydihydroflavonol-6-C-beta-D-glucopyranoside (3) and 3-C-beta-D
      glucopyranoside-2,4,6-trihydroxymethylbenzoate (8), together with five known
      flavonoid-6-C-glucosides (2, 4-7). Their structures were elucidated using 1D and
      2D NMR spectroscopic analysis. The absolute stereochemistry in compounds 1 and 3
      were established with the help of CD data analysis and comparison with the
      literature data analysis. All the isolated compounds (1-8) were assessed for
      promoting the osteoblast differentiation using primary culture of rat osteoblast
      as an in vitro system. Compounds 1-3 and 5 significantly increased osteoblast
      differentiation as assessed by alkaline phosphatase activity.

PMID- 19596574
TI  - Respiratory syncytial virus fusion inhibitors. Part 7: structure-activity
      relationships associated with a series of isatin oximes that demonstrate
      antiviral activity in vivo.
AB  - A series of bezimidazole-isatin oximes were prepared and profiled as inhibitors
      of respiratory syncytial virus (RSV) replication in cell culture. Structure
      activity relationship studies were directed toward optimization of antiviral
      activity, cell permeability and metabolic stability in human liver micorosomes
      (HLM). Parallel combinatorial synthetic chemistry was employed to functionalize
      isatin oximes via O-alkylation which quickly identified a subset of small,
      lipophilic substituents that established good potency for the series. Further
      optimization of the isatin oxime derivatives focused on introduction of nitrogen
      atoms to the isatin phenyl ring to provide a series of aza-isatin oximes with
      significantly improved PK properties. Several aza-isatin oximes analogs displayed
      targeted metabolic stability in HLM and permeability across a confluent monolayer
      of CaCo-2 cells. These studies identified several compounds, including 18i, 18j
      and 18n that demonstrated antiviral activity in the BALB/c mouse model of RSV
      infection following oral dosing.

PMID- 19596575
TI  - Design, synthesis and biological evaluation of new potent and highly selective
      ROS1-tyrosine kinase inhibitor.
AB  - ROS1 protein is a receptor tyrosine kinase that has been reported mainly in
      meningiomas and astrocytomas, and until now, there is no selective inhibitor for
      this kinase. In this study, we illustrate for the synthesis of a highly potent
      and selective inhibitor for ROS1 kinase. The synthesized compound 1 was tested
      initially at a single dose concentration of 10 microM over 45 different kinases.
      At this concentration, a 94% inhibition of the enzymatic activity of ROS1 kinase
      was observed, while the inhibition in activity was below 30% in all of the other
      kinases. The pyrazole compound 1 was further tested in a 10-dose IC(50) mode and
      showed an IC(50) value of 199 nM for ROS1 kinase. The compound 1 can be used as a
      promising lead for the development of new selective inhibitors for ROS1 kinase,
      and it may open the way for new selective therapeutics for astrocytomas.

PMID- 19596576
TI  - Substituted pyrimidines as cannabinoid CB1 receptor ligands.
AB  - Cannabinoid CB1 receptors have been the avenue of extensive studies since the
      first clinical results of rimonabant (SR141716) for the treatment of obesity and
      obesity-related metabolic disorders were reported in 2001. To further evaluate
      the properties of CB receptors, we have designed and efficiently prepared a
      series of substituted pyrimidines based on chemical structure of Merck's
      taranabant, a cannabinoid CB1 receptor inverse agonist. Noticeably, N4-((2S,3S)-3
      (3-bromophenyl)-4-(4-chlorophenyl)butan-2-yl)-N6-butylpyrimidine-4,6-diamine
      (13b) demonstrated good binding affinity and decent selectivity for CB1 receptor
      (IC(50)=16.3nM, CB2/CB1=181.6).

PMID- 19596577
TI  - Synthesis and enzymatic evaluation of novel partially fluorinated thiol dual
      ACE/NEP inhibitors.
AB  - A novel family of peptidomimetics incorporating fluoroalkyl groups, mainly a
      trifluoromethyl, in alpha-position to a zinc(II)-binding thiol function, was
      synthesized in solution as well as in solid-phase. These compounds showed
      inhibitory potency in the nanomolar range against both angiotensin-converting
      enzyme (ACE) and neutral endopeptidase (NEP), whereas no inhibition of endothelin
      converting enzyme-1 (ECE-1) was observed. The trifluoromethyl-derivatives were
      more potent than the parent unfluorinated analogues in the case of ACE, and less
      potent in the case of NEP.

PMID- 19596578
TI  - Polyethylenimine effectively induces, stabilizes, and regulates intramolecular G
      quadruplexes.
AB  - The interaction between polyethylenimine (PEI) and telomeric DNA was studied. The
      results demonstrated that PEI could effectively induce, stabilize, and regulate
      intramolecular G-quadruplexes. The mechanism for these results has been
      discussed, and was estimated to be condensation effect of PEI.

PMID- 19596579
TI  - C5-Modified nucleosides exhibiting anticancer activity.
AB  - We describe (i) a simple method for the synthesis of C5-modified nucleosides from
      5-iodo-2'-deoxyuridine and (ii) their activity against six types of human cancer
      cell lines (HCT15, MM231, NCI-H23, NUGC-3, PC-3, ACHN). We generated nitrile
      oxides in situ from oximes using a commercial bleaching agent; their
      cycloadditions with 5-ethynyl-2'-deoxyuridine yielded isoxazole derivatives
      possessing activity against the cancer cell lines. We synthesized several azides
      from benzylic bromides and their click reactions with 5-ethynyl-2'-deoxyuridine
      provided triazole derivatives.

PMID- 19596580
TI  - Hemicellulose dressing versus rayon dressing in the re-epithelialization of split
      thickness skin graft donor sites: a multicenter study.
AB  - The aim of this study was to compare the effectiveness of a hemicellulose
      dressing with that of rayon dressing in the healing of split-thickness skin graft
      donor sites. Twenty-eight patients were selected from five different hospitals
      and randomized into two groups: hemicellulose dressing group and rayon dressing
      group. All patients underwent split-thickness skin grafting for various reasons,
      and the skin graft donor site wounds were covered with hemicellulose dressing
      (n=14) or rayon dressing (n=14). The donor site was assessed on postoperative
      days 1, 7, 14, 21, and 28 for hyperemia, pruritus, pain, exudate level, and
      adherence of the wound dressing. At the 60-day follow-up visit, the donor site
      was assessed again for pruritus and pain. Touch-pressure, thermal, and pain
      sensibility tests were performed preoperatively and on postoperative day 60
      together with the assessment of color and texture of the re-epithelialized area.
      In all patients, re-epithelialization was completed between 14 and 21 days after
      surgery. There were no significant differences between the two groups with regard
      to pain, hyperemia, pruritus, exudate, and final appearance (color and texture)
      of the skin graft donor site. The rayon dressing provided significantly better
      adherence than the hemicellulose dressing, and both dressings showed similar
      results with regard to the parameters evaluated when used in the treatment of
      split-thickness skin graft donor sites.

PMID- 19596581
TI  - Effect of bone marrow-derived mononuclear cells on nerve regeneration in the
      transection model of the rat sciatic nerve.
AB  - Bone marrow-derived stem cells enhance the rate of regeneration and clinical
      improvement in nerve injury, spinal cord injury and brain infarction. Recent
      experiments in rat spinal cord demyelination showed that remyelination was
      specific to intravenous delivery of the bone marrow-derived mononuclear cell (BM
      MNC) fraction, although the specific role of this fraction in peripheral nerve
      regeneration has not been examined. Therefore we evaluated the role of BM-MNCs in
      peripheral nerve regeneration in the rat sciatic nerve transection model. After
      anesthesia, the right sciatic nerve of 20 adult-male Wistar rats was transected
      under an operating microscope. In the test group, the cut ends of the nerve were
      approximated with two epineural microsutures, the gap was filled with rat BM-MNCs
      and the approximated nerve ends were covered with fibrin glue. In the control
      group, the transected nerve ends were repaired with two epineural microsutures
      and fibrin sealant only. Histological assessment of the nerve was performed 30
      days and 60 days after the operation and regenerative changes were compared
      between the two groups. The recovery after nerve anastamosis was far better in
      the test group at both 30 days and 60 days. There was a statistically significant
      difference in axonal regeneration, remyelination and myelin thickness at sites
      5mm and 10mm from the site of repair of the nerve. Schwann cell proliferation and
      degenerative changes were more prevalent in the controls. This study demonstrates
      that local delivery of BM-MNCs (which can be isolated easily from bone marrow
      aspirates) into injured peripheral nerve increases the rate and degree of nerve
      regeneration. The present study highlights the role of BM-MNCs in peripheral
      nerve regeneration.

PMID- 19596582
TI  - Synthesis and evaluation of a novel series of quinoline derivatives with
      immunosuppressive activity.
AB  - A series of quinoline derivatives were synthesized and their immunosuppressive
      activity and cytotoxicity were evaluated with a T-cell functional assay and MTT
      method, respectively. Most of 5,7-dimethoxyquinolin-4-yl ortho-substituted
      benzoate derivatives (18, 22, 24, 28, 31 and 37) showed a quite stronger
      inhibitory activity compared to other analogs. Among the synthesized compounds,
      5,7-dimethoxyquinolin-4-yl 2,6-dichlorobenzoate (22) and 5,7-dimethoxyquinolin-4
      yl 4-methylbenzenesulfonate (40) exhibited a potent inhibitory activity without
      significant cytotoxicity at 10 microM concentration. The preliminary mechanism of
      the active compounds 22 and 40 was further clarified based on the fluorescence
      activated cell sorter (FACS) assay, and the compounds exerted immunosuppressive
      activity via inhibiting the T cell activation in a dose dependent manner.

PMID- 19596583
TI  - Synthesis and evaluation of a novel 2-azabicyclo[2.2.2]octane class of long chain
      fatty acid elongase 6 (ELOVL6) inhibitors.
AB  - A series of novel 2-azabicyclo[2.2.2]octane derivatives was synthesized and
      evaluated as long chain fatty acid elongase 6 (ELOVL6) inhibitors. Screening of
      our corporate chemical collections against ELOVL6 resulted in the identification
      of lead 1. Exploratory chemistry efforts were applied to lead 1 to identify the
      orally available, potent, and selective ELOVL6 inhibitor 28a.

PMID- 19596584
TI  - Changes in ultrastructure and histochemistry of two red macroalgae strains of
      Kappaphycus alvarezii (Rhodophyta, Gigartinales), as a consequence of ultraviolet
      B radiation exposure.
AB  - Ultraviolet radiation (UVR) affects macroalgae in many important ways, including
      reduced growth rate, reduction of primary productivity and changes in cell
      biology and ultrastructure. Among red macroalgae, Kappaphycus alvarezii is of
      economic interest by its production of kappa carrageenan. Only a few reports have
      examined the changes in macroalgae ultrastructure and cell biology resulting from
      UVB radiation exposure. Therefore, we examined two strains of K. alvarezii (green
      and red) exposed to UVB for 3 h per day during 28 days and then processed them
      for histochemical and electron microscopy analysis. Reaction with Toluidine Blue
      showed an increase in the thickness of the cell wall and Periodic Acid-Schiff
      stain showed a decrease in the number of starch grains. UVBR also caused changes
      in the ultrastructure of cortical and subcortical cells, which included increased
      thickness of the cell wall and number of free ribosomes and plastoglobuli,
      reduced intracellular spaces, changes in the cell contour, and destruction of
      chloroplast internal organization. Based on these lines of evidence, it was
      evident by the ultrastructural changes observed that UVBR negatively affects
      intertidal macroalgae and, by extension, their economic viability.

PMID- 19596585
TI  - External radiation assessment in a wet phosphoric acid production plant.
AB  - The factories dedicated to the production of phosphoric acid by the so-called wet
      acid method are usually considered typical NORM industries, because the phosphate
      rock used as raw material usually contains high concentrations of (238)U-series
      radionuclides. The magnitude and behaviour of the radionuclides involved in the
      production process revealed the need to determine its dosimetric impact on
      workers. This work aims to partially compensate this lack of knowledge through
      the determination of external effective dose rates at different zones in the
      process at a typical plant located in the southwest of Spain. To this end, two
      dosimetric sampling campaigns have been carried out at this phosphoric acid
      production plant. The first sampling was carried out when phosphate rocks
      originating in Morocco were processed, and the second one when phosphate rock
      processed came from the Kola Peninsula (Russia Federation). This differentiation
      was necessary because the activity concentrations are almost one order of
      magnitude higher in Moroccan phosphate rock than in Kola phosphate rock. The
      results obtained have reflected external dose rate enhancements as high as
      1.4microSvh(-1) (i.e., up to thirty times the external exposition due to
      radionuclides in unperturbed soils) at several points in the facility,
      particularly where the digested rock (pulp) is filtered. However, the most
      problematic points are characterised by a small occupation factor. That means
      that the increment in the annual effective external gamma dose received by the
      most-exposed worker is clearly below 1mSv (European Commission limit for the
      general population) under normal production. Nevertheless, special care in the
      design and schedule of cleaning and maintaining work in the areas with high doses
      should be taken in order to avoid any possibility of exceeding the previously
      mentioned general population limit. In addition, the results of the dosimetric
      campaign showed no clear correlation between (226,228)Ra activity concentrations
      in the material fluxing during the process (the most important radionuclides from
      the dosimetric point of view) and the external dose rates. Furthermore, any
      general dependence of the origin of the rock (i.e., on their radioactive
      contents) on the external effective dose rate measured has not been observed.
      These latter findings could be a consequence of three effects: (1) a variable
      radiation shielding at the different points along the process, (2) a changing
      geometry of irradiation (from a rock pile up to a thin-layered pulp passing
      through a solid mass inside pipes and deposits), and (3) the existence of a
      "memory effect", or background contamination in the installation equipment due to
      the presence of radionuclide-enriched scales and sludges in pipes and deposits.

PMID- 19596586
TI  - Neutrophil recovery in elderly breast cancer patients receiving adjuvant
      anthracycline-containing chemotherapy with pegfilgrastim support.
AB  - Shortening duration of chemotherapy-induced neutropenia may reduce risk of
      infection and aid subsequent chemotherapy delivery. Cycle 1 neutrophil recovery
      was evaluated in 59 elderly women with breast cancer receiving adjuvant FEC100 (5
      fluorouracil 500 mg/m(2), epirubicin 100mg/m(2) and cyclophosphamide 500 mg/m(2))
      and randomized to pegfilgrastim primary prophylaxis (PP) from cycle 1, or
      secondary prophylaxis (SP, i.e., subsequent to a neutropenic event [no G-CSF in
      cycle 1]). In cycle 1, grade 4 neutropenia occurred in 77% (PP; N=30) and 72%
      (SP; N=29). Duration of grade 3-4 neutropenia was shorter with pegfilgrastim than
      without. Mean absolute neutrophil count (ANC) recovered above 1.0 x 10(9)/L by
      day 9 (pegfilgrastim) versus days 16-18 (without). At last observation (> or =day
      14+/-2), no PP patient had ANC <1.0 x 10(9)/L versus approximately 25% of those
      receiving no pegfilgrastim. In conclusion, cycle 1 pegfilgrastim improved
      recovery from severe neutropenia in elderly breast cancer patients receiving
      adjuvant FEC100.

PMID- 19596587
TI  - Geriatric nutritional risk index as a screening tool for malnutrition in patients
      on chronic peritoneal dialysis.
AB  - BACKGROUND: Malnutrition is common among peritoneal dialysis (PD) patients.
      Recently, the Geriatric Nutrition Risk Index (GNRI) was found to be a reliable
      tool for screening malnutrition in hemodialysis patients. However, the GNRI has
      not been validated in PD patients. METHODS: We studied 314 unselected, adult PD
      patients from a single dialysis unit. We compared their GNRI scores with their
      comprehensive Malnutrition-Inflammation Scores (MIS) and 7-point Subjective
      Global Assessment (SGA) scores. We randomly selected 106 patients for a repeated
      assessment, and the changes in their three indices were compared. RESULTS:
      Baseline GNRI was significantly correlated with MIS (r = -0.487, P < .0001) and
      SGA (r = 0.234, P < .0001). When MIS >or=6 was defined as malnutrition, the
      sensitivity and specificity of GNRI <or=93 in predicting malnutrition were 68.0%
      and 67.7%, respectively. When SGA <or=5 was used to define malnutrition, the
      sensitivity and specificity were 54.5% and 71.1%, respectively. The change in
      GNRI was correlated with the change in MIS (r = -0.244, P = .012) and overall SGA
      score (r = 0.266, P = .006), respectively. When an increase in MIS was defined as
      a worsening of nutrition, the sensitivity and specificity of GNRI were 45.7% and
      81.7%, respectively. When a decrease in SGA was used to define a worsening of
      nutrition, the sensitivity and specificity were 42.3% and 87.0%, respectively.
      CONCLUSIONS: Although GNRI is significantly correlated with other nutritional
      indices, it is not sensitive for screening malnutrition in PD patients. Serial
      measurements of GNRI are also not sensitive in detecting a change in nutritional
      status. Further study is needed to identify a simple and reliable tool for the
      assessment and monitoring of nutritional status in PD patients.

PMID- 19596589
TI  - Dietary intakes and biochemical status of B vitamins in a group of children
      receiving dialysis.
AB  - OBJECTIVE: We investigated the dietary intake and biochemical status of B
      vitamins (thiamin, riboflavin, vitamin B6, and vitamin B12) in a group of mainly
      unsupplemented children with endstage renal disease receiving dialysis, to
      determine if B vitamin supplementation is indicated. DESIGN: This was a cross
      sectional, observational clinical trial. SETTING: Children with endstage renal
      disease were receiving dialysis, under the care of Renal Services, at Starship
      Children's Health (Grafton, Auckland, New Zealand). PATIENTS: We studied 12
      children (including 7 girls, and 8 children receiving peritoneal dialysis) mean
      age 7.8 +/- 5.3 years (SD). INTERVENTION: Three-day diet records were collected
      and analyzed with FoodWorks software. Blood was collected for vitamin assay
      testing. MAIN OUTCOME MEASURE: Dietary intake of B vitamins was measured as a
      percentage of recommended dietary intake (RDI) or adequate intakes (AIs) for age.
      Biochemical status was measured as the concentration of each B vitamin compared
      with reference ranges. RESULTS: Mean intakes from diet alone comprised <100% of
      the RDI or AI for each B vitamin. Mean intakes, with nutritional support, reached
      >100% of the RDI or AI for each B vitamin. All children achieved >100% RDI or AI
      for thiamin, riboflavin, and vitamin B12. Two children who were not receiving
      nutritional support received <100% of the RDI for vitamin B6. Blood levels of B
      vitamins were normal to high, compared with reference ranges, for each B vitamin
      in all children, indicating adequate status. CONCLUSIONS: Intakes were adequate
      in the majority of children. Status was adequate in all children. In this group
      of children undergoing dialysis, B-vitamin supplementation was not indicated.

PMID- 19596590
TI  - Implementation of graphic user interface screen capture solution for workflow
      assessment of abdominal MR examinations valuable tool to analyze discrepancies in
      expected and experienced MR table time.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to assess if graphical user
      interface screen-capture software applied to a magnetic resonance (MR) hardware
      console could nonintrusively allow the analysis of discrepancies between expected
      and experienced MR table time. MATERIALS AND METHODS: Individual MR examination
      acquisition processes were captured in audio-video interleave streams for 10
      patients who underwent comprehensive liver MR imaging. These audio-video streams
      were dissected into periods of true image data acquisition, scanner activity
      without direct image data acquisition, and scanner inactivity. RESULTS: Total
      expected time required for standardized liver MR image acquisition was estimated
      at 15 minutes. Experienced table times varied highly, ranging from 19:00 to 58:08
      minutes. Image data acquisition occurred during approximately 58% (range, 43.3%
      73.7%) of overall table time. Image data were obtained approximately 77% (range,
      65.6%-87.0%) of the time the scanner spent active. CONCLUSION: Graphical user
      interface screen-capture software installed on an MR console nonintrusively
      revealed significant periods of table time spent not obtaining true image data
      and explained discrepancies between expected and experienced MR table times.
      Table-time calculations using Digital Imaging and Communications in Medicine
      image headers and scanner-logged time stamps are underestimations of true table
      time because they do not take into account some scanner activities not directly
      leading to image formation.

PMID- 19596588
TI  - Relationship between adiposity and cardiovascular risk factors in prevalent
      hemodialysis patients.
AB  - OBJECTIVE: Increased body mass index (BMI) is associated with reduced all-cause
      and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk
      increases with BMI in the general population. In the general population, obesity
      is associated with inflammation, decreased high-density lipoprotein (HDL)
      cholesterol, increased low-density lipoprotein (LDL) cholesterol, and
      triglycerides (TGs), all risk factors for CV disease. Low-density lipoprotein
      cholesterol does not predict CV risk in HD, whereas increased C-reactive protein
      and interleukin-6 (IL-6), low HDL and apolipoprotein (apo) AI, and increased
      fasting TGs do predict risk. Renal failure is associated with dyslipidemia and
      inflammation in normal-weight patients. We hypothesized that the effects of
      obesity may be obscured by renal failure in HD. METHODS: We explored the
      relationship between adipose tissue pools and distribution, i.e., subcutaneous
      adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by magnetic
      resonance imaging) and measures of inflammation (C-reactive protein, IL-6,
      ceruloplasmin, and alpha1 acid glycoprotein), HDL and LDL cholesterol, total TGs,
      apo AI, apo B, apo CII (an activator of lipoprotein lipase), apo CIII (an
      inhibitor of lipoprotein lipase), and the adipokines, leptin and adiponectin, in
      48 patients with prevalent HD. RESULTS AND CONCLUSIONS: Total TG concentrations
      were positively correlated with VAT controlled for age, sex, and weight. Both apo
      CII and apo CIII were correlated only with VAT. Adiponectin was inversely
      correlated with VAT, and leptin was positively associated with SAT. C-reactive
      protein and alpha1 acid glycoprotein were weakly associated with SAT, whereas
      ceruloplasmin was strongly associated with VAT according to multiple regression
      analysis. In contrast, apo B, LDL, apo AI, HDL, and IL-6 were not correlated with
      any measure of body composition, potentially mitigating the effects of obesity in
      HD.

PMID- 19596591
TI  - Comparative evaluation of the fecal-tagging quality in CT colonography: barium
      vs. iodinated oral contrast agent.
AB  - RATIONALE AND OBJECTIVES: The purpose of this evaluation was to compare the
      tagging quality of a barium-based regimen with that of iodine-based regimens for
      computed tomographic (CT) colonography. MATERIALS AND METHODS: Tagging quality
      was assessed retrospectively in three different types of fecal-tagging CT
      colonographic cases: 24 barium-based cases, 22 nonionic iodine-based cases, and
      24 ionic iodine-based cases. For the purpose of evaluation, the large intestine
      was divided into six segments, and the tagging homogeneity of a total of 420
      segments (70 patients) was graded by three blinded readers from 0 (heterogeneous)
      to 4 (homogeneous). RESULTS: For barium-based cases, the average score for the
      three readers was 2.4, whereas it was 3.4 for nonionic iodine and 3.6 for ionic
      iodine. The percentages of segments that were assigned scores of 4 (excellent
      tagging [100%]) were 11.6%, 61.9%, and 72.9% for the barium-based, nonionic
      iodine-based, and ionic iodine-based regimens, respectively. The homogeneity
      scores of iodine-based fecal-tagging regimens were significantly higher than
      those of the barium-based fecal-tagging regimen (P < .001). The CT attenuation
      values of tagging in the cases were also assessed: the minimum and maximum values
      were significantly higher for the iodine-based regimens than for the barium-based
      regimen (P < .001). CONCLUSIONS: The iodine-based fecal-tagging regimens provide
      significantly greater homogeneity in oral-tagging fecal material than the barium
      based fecal-tagging regimen. Iodine-based fecal-tagging regimens can provide an
      appropriate method for use in nonlaxative or minimum-laxative CT colonography.

PMID- 19596592
TI  - Reliability of quantitative ultrasound measures of the biceps and supraspinatus
      tendons.
AB  - RATIONALE AND OBJECTIVES: Ultrasound is a proven method for examining soft tissue
      structures, including tendons, and recently quantitative ultrasound has become
      more prevalent in research settings. However, limited reliability data have been
      published for these new quantitative ultrasound measures. The main objective of
      this study was to quantify the reliability and measurement error of multiple
      quantitative ultrasound imaging protocols for the biceps and supraspinatus
      tendons. MATERIALS AND METHODS: Two examiners captured ultrasound images of the
      non-dominant long head of the biceps tendon and supraspinatus tendon from 15 able
      bodied participants and five manual wheelchair users. Each examiner captured two
      images per subject under two different preparations, which included subject
      positioning and reference marker placement. Image processing (reading) was
      performed twice to compute nine quantitative ultrasound measures of grayscale
      tendon appearance using first-order statistics and texture analysis.
      Generalizability theory was applied to compute interrater and intrarater
      reliability using the coefficient of dependability (Phi) for multiple study
      design protocols. RESULTS: Interrater reliability was generally low (0.26 < Phi <
      0.82), and it is recommended that a single evaluator capture all images for
      quantitative ultrasound protocols. Most of the quantitative ultrasound measures
      (n = 14 of 18) exhibited at least moderate (Phi > 0.50) intrarater reliability
      for a single image captured under one preparation and read once. CONCLUSION: By
      following a protocol designed to minimize measurement error, one can increase the
      reliability of quantitative ultrasound measures. An appropriately designed
      protocol will allow quantitative ultrasound to be used as an outcome measure to
      identify structural changes within tendons.

PMID- 19596594
TI  - Dual energy versus single energy MDCT: measurement of radiation dose using adult
      abdominal imaging protocols.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to measure the radiation dose
      of dual-energy and single-energy multidetector computed tomographic (CT) imaging
      using adult liver, renal, and aortic imaging protocols. MATERIALS AND METHODS:
      Dual-energy CT (DECT) imaging was performed on a conventional 64-detector CT
      scanner using a software upgrade (Volume Dual Energy) at tube voltages of 140 and
      80 kVp (with tube currents of 385 and 675 mA, respectively), with a 0.8-second
      gantry revolution time in axial mode. Parameters for single-energy CT (SECT)
      imaging were a tube voltage of 140 kVp, a tube current of 385 mA, a 0.5-second
      gantry revolution time, helical mode, and pitch of 1.375:1. The volume CT dose
      index (CTDI(vol)) value displayed on the console for each scan was recorded.
      Organ doses were measured using metal oxide semiconductor field-effect transistor
      technology. Effective dose was calculated as the sum of 20 organ doses multiplied
      by a weighting factor found in International Commission on Radiological
      Protection Publication 60. Radiation dose saving with virtual noncontrast imaging
      reconstruction was also determined. RESULTS: The CTDI(vol) values were 49.4 mGy
      for DECT imaging and 16.2 mGy for SECT imaging. Effective dose ranged from 22.5
      to 36.4 mSv for DECT imaging and from 9.4 to 13.8 mSv for SECT imaging. Virtual
      noncontrast imaging reconstruction reduced the total effective dose of multiphase
      DECT imaging by 19% to 28%. CONCLUSION: Using the current Volume Dual Energy
      software, radiation doses with DECT imaging were higher than those with SECT
      imaging. Substantial radiation dose savings are possible with DECT imaging if
      virtual noncontrast imaging reconstruction replaces precontrast imaging.

PMID- 19596593
TI  - Radiologist evaluation of an X-ray tube-based diffraction-enhanced imaging
      prototype using full-thickness breast specimens.
AB  - RATIONALE AND OBJECTIVES: Conventional mammographic image contrast is derived
      from x-ray absorption, resulting in breast structure visualization due to density
      gradients that attenuate radiation without distinction between transmitted,
      scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for
      increased contrast with decreased radiation dose compared to conventional
      mammographic imaging because of monochromatic x-rays, its unique refraction-based
      contrast mechanism, and excellent scatter rejection. However, a lingering
      drawback to the clinical translation of DEI has been the requirement for
      synchrotron radiation. MATERIALS AND METHODS: The authors' laboratory developed a
      DEI prototype (DEI-PR) using a readily available tungsten x-ray tube source and
      traditional DEI crystal optics, providing soft tissue images at 60 keV. Images of
      full-thickness human breast tissue specimens were acquired on synchrotron-based
      DEI (DEI-SR), DEI-PR, and digital mammographic systems. A panel of expert
      radiologists evaluated lesion feature visibility and correlation with pathology
      after receiving training on the interpretation of refraction contrast
      mammographic images. RESULTS: For mammographic features (mass, calcification), no
      significant differences were detected between the DEI-SR and DEI-PR systems.
      Benign lesions were perceived as better seen by radiologists using the DEI-SR
      system than the DEI-PR system at the [111] reflectivity, with generalizations
      limited by small sample size. No significant differences between DEI-SR and DEI
      PR were detected for any other lesion type (atypical, cancer) at either crystal
      reflectivity. CONCLUSIONS: Thus, except for benign lesion characterizations, the
      DEI-PR system's performance was roughly equivalent to that of the traditional DEI
      system, demonstrating a significant step toward clinical translation of this
      modality for breast cancer applications.

PMID- 19596595
TI  - An integrated model for radiology education: development of a year-long
      curriculum in imaging with focus on ambulatory and multidisciplinary medicine.
AB  - RATIONALE AND OBJECTIVE: In 2004, Harvard Medical School initiated a pilot
      program, the Cambridge Integrated Clerkship, in which students study the core
      third-year medical disciplines in a longitudinal year long experience. In this
      paper, the authors describe the design of the radiology portion of this program
      and compare outcomes to those of students in a traditional curriculum. MATERIALS
      AND METHODS: Students in the integrated curriculum were compared to students in
      traditional clerkships on the basis of Objective Structured Clinical Examination
      cases, final exams, fourth-year comprehensive exam scores, and choice of
      specialty. RESULTS: Scores on Objective Structured Clinical Examination cases and
      imaging final exams were not statistically different between the two groups, but
      Integrated Clerkship students had statistically lower scores on final exams.
      Integrated Clerkship students scored higher on the fourth-year radiology
      comprehensive exam than traditional students, but differences were not
      statistically significant. Choice of radiology as a specialty was not
      statistically different between the two groups. CONCLUSIONS: Teaching radiology
      in an integrated year long curriculum is feasible, with a minimal drop in exam
      scores but no changes in other evaluative measures and no decrease in the choice
      of radiology as a specialty. The program may give students a better appreciation
      of the role of radiology in an ambulatory setting and in relationship to other
      specialties.

PMID- 19596596
TI  - Endovascular aortic arch repair: hopes and certainties.
AB  - For aneurysms and dissections involving the aortic arch, the traditional
      treatment is open surgical repair requiring cardiopulmonary bypass and deep
      hypothermic circulatory arrest. Reported mortality rates range from 7% to 17% and
      neurologic injury rates range from 4% to 12%. Since the first clinical
      applications of endovascular repair in the early 1990s, this less-invasive
      treatment modality has evolved steadily. For the treatment of aortic arch
      pathologies, combined open and endovascular strategies (hybrid procedures) have
      gained a widespread implementation. Evidence to date proves the feasibility of
      open surgical branch re-vascularisation followed by endovascular repair into the
      proximal arch. For hybrid procedures, mortality and stroke rates are given as 0
      20%, and 0-8%, respectively. Alternative approaches using fenestrated and
      branched stent grafts have been considered. Although this technique is
      challenging and devices are not available widely, it is anticipated that this new
      technique will expand the range of aortic arch pathologies that can be treated by
      endovascular means.

PMID- 19596597
TI  - A 15-year experience with combined vascular reconstruction and free flap transfer
      for limb-salvage.
AB  - OBJECTIVES: To evaluate the results and complications of combined simultaneous
      arterial re-vascularisation and free flap transfer in patients with critical limb
      ischaemia and large soft-tissue defects that would otherwise have required major
      amputation. DESIGN: Retrospective analysis of all combined procedures performed
      between 1993 and 2007 with regard to complications and outcome. MATERIALS AND
      METHODS: Seventy-eight procedures were performed in 76 patients with a mean age
      of 60 years (range: 18-80 years). The majority had diabetes (70.5%). Follow-up
      was obtained from hospital charts and telephone contacts with patients or GPs.
      RESULTS: The limb-salvage rate was 93% after 1 year, 80% after 3 years and 71%
      after 5 years. Perioperative complications occurred in 50% of the patients; six
      out of 78 (7.7%) arterial reconstructions and 13 out of 78 (16.7%) flaps had to
      be revised during the early postoperative period. However, most flaps could be
      saved by a secondary procedure resulting in an early failure (amputation) rate of
      6%. In-hospital mortality was 3.8%. End-stage renal disease was the only factor
      predicting limb loss. In total, 65% of the patients survived and were able to
      walk on their reconstructed limb at 1-year follow-up. Combined survival and limb
      salvage rates were 85%, 66% and 51% after 1, 3 and 5 years. CONCLUSIONS: Combined
      arterial re-vascularisation and free flap transfer can be performed safely with
      acceptable morbidity and mortality and should be considered for every mobile
      patient with large soft-tissue deficit (>10cm(2)) without end-stage renal disease
      prior to major amputation.

PMID- 19596599
TI  - Obstructive sleep apnea and depression.
AB  - There are high rates of depression in people with obstructive sleep apnea (OSA)
      in both community and clinical populations. A large community study reported a
      rate of 17% and reports for sleep clinic samples range between 21% and 41%. A
      large cohort study found OSA to be a risk factor for depression, but we are
      unaware of any longitudinal study of the reverse association. However
      correlations have not generally been found in smaller studies. Well-designed
      longitudinal studies are needed to examine temporal relationships between the two
      conditions and further research is needed to establish the role of confounders,
      and effect modifiers such as gender, in any apparent relationship. Symptoms
      common to OSA and depression, such as sleepiness and fatigue, are obstacles to
      determining the presence and severity of one condition in the presence of the
      other, in research and clinically. Sleep clinicians are advised to consider
      depression as a likely cause of sleepiness and fatigue. Several possible causal
      mechanisms linking OSA and depression have been proposed but not established.
      Patients who have depression as well as OSA appear worse off than those with OSA
      only, and depressive symptoms persist in at least some patients in short term
      studies of treatment for OSA. Direct treatment of depression in OSA might improve
      acceptance of therapy, reduce sleepiness and fatigue and improve quality of life,
      but intervention trials are required to answer this question.

PMID- 19596598
TI  - Lower-extremity arteriovenous access for haemodialysis: a systematic review.
AB  - BACKGROUND: The lower extremity is increasingly used as an access site in end
      stage renal disease patients. However, reports present conflicting results,
      creating confusion regarding the feasibility and outcomes. Our objective is to
      review the available literature and analyse the patency rates and complications
      of various types of lower-extremity arteriovenous access. METHODS: An Internet
      based literature search was performed using MEDLINE to identify all published
      reports on lower-extremity vascular access. The analysis involved studies
      comprising at least 10 arteriovenous accesses with both inflow and outflow
      vessels in the lower extremity, and reporting on patency rates and access-related
      complications. The weighted mean patency rates were calculated, and the chi
      square (chi(2)) test was used to evaluate the differences in the complication
      rates in the subgroups of patients identified. RESULTS: Three main types of lower
      extremity vascular access were identified: the upper thigh prosthetic, the mid
      thigh prosthetic and the femoral vein transposition arteriovenous access. There
      are limited data on saphenous vein loop grafts, which report poor results. The
      weighted mean primary patency rates at 12 months were 48%, 43% and 83%,
      respectively. The weighted mean secondary patency rates at 12 months were 69%,
      67% and 93%, respectively. Access loss as a result of infection was more common
      in upper thigh and mid-thigh grafts than femoral vein transposition arteriovenous
      access (18.40%, 18.33% vs. 1.61%; P<0.05). Ischaemic complications rates were
      higher in autologous than prosthetic arteriovenous access (20.97% vs. 7.18%,
      P<0.05). CONCLUSIONS: Lower-extremity vascular access has acceptable results in
      terms of patency, with femoral vein transposition having better patency rates
      than femoral grafts. Autologous access is associated with less infective
      complications, however, at the expense of increased ischaemic complications
      rates. Further research with randomised trials is required to assess the outcomes
      of lower-extremity vascular access.

PMID- 19596600
TI  - Quantitative analysis of Earth's field NMR spectra of strongly-coupled
      heteronuclear systems.
AB  - In the Earth's magnetic field, it is possible to observe spin systems consisting
      of unlike spins that exhibit strongly coupled second-order NMR spectra. Such
      spectra result when the J-coupling between two unlike spins is of the same order
      of magnitude as the difference in their Larmor precession frequencies. Although
      the analysis of second-order spectra involving only spin-(1/2) nuclei has been
      discussed since the early days of NMR spectroscopy, NMR spectra involving spin
      (1/2) nuclei and quadrupolar (I>(1/2)) nuclei have rarely been treated. Two
      examples are presented here, the tetrahydroborate anion, BH4-, and the ammonium
      cation, NH4+. For the tetrahydroborate anion, (1)J((11)B,(1)H)=80.9Hz, and in an
      Earth's field of 53.3microT, nu((1)H)=2269Hz and nu((11)B)=728Hz. The (1)H NMR
      spectra exhibit features that both first- and second-order perturbation theory
      are unable to reproduce. On the other hand, second-order perturbation theory
      adequately describes (1)H NMR spectra of the ammonium anion, (14)NH4+, where
      (1)J((14)N,(1)H)=52.75Hz when nu((1)H)=2269Hz and nu((14)N)=164Hz. Contrary to an
      early report, we find that the (1)H NMR spectra are independent of the sign of
      (1)J((14)N,(1)H). Exact analysis of two-spin systems consisting of quadrupolar
      nuclei and spin-(1/2) nuclei are also discussed.

PMID- 19596601
TI  - High-resolution solid-state NMR structure of alanyl-prolyl-glycine.
AB  - We present a de novo high-resolution structure of the peptide Alanyl-Prolyl
      Glycine using a combination of sensitive solid-state NMR techniques that each
      yield precise structural constraints. High-quality (13)C-(13)C distance
      constraints are extracted by fitting rotational resonance width (R(2)W)
      experiments using Multimode Multipole Floquet Theory and experimental chemical
      shift anisotropy (CSA) orientations. In this strategy, a structure is first
      calculated using DANTE-REDOR and torsion angle measurements and the resulting
      relative CSA orientations are used as an input parameter in the (13)C-(13)C
      distance calculations. Finally, a refined structure is calculated using all the
      constraints. We investigate the effect of different structural constraints on
      structure quality, as determined by comparison to the crystal structure and also
      self-consistency of the calculated structures. Inclusion of all or subsets of
      these constraints into CNS calculations resulted in high-quality structures
      (0.02A backbone RMSD using all 11 constraints).

PMID- 19596603
TI  - "They (ARVs) are my life, without them I'm nothing"--experiences of patients
      attending a HIV/AIDS clinic in Johannesburg, South Africa.
AB  - This paper is a part of a larger study that explores the "social complexity" of
      antiretroviral therapy (ART), in resource-limited environments. Drawing on in
      depth interviews with a sample of 44 patients in an urban HIV/AIDS clinic in
      Johannesburg, South Africa, this paper examines how people with HIV/AIDS
      conceptualize their illness and its treatment in this context. The paper
      concludes that the fear of stigma plays a significant role in patients'
      experiences throughout the disease trajectory. Yet, demonstrates that there are
      indications that ARVs are transforming the experience of living with HIV/AIDS and
      a process of normalisation is taking place. Despite the resource-limited context
      and, often, lack of family and community support, patients see the ARVs as 'life
      saving' and express their long-term commitment to adhere to the drug regimen as
      well as their trust in health professionals.

PMID- 19596602
TI  - Molecular modeling of human cytochrome P450 2W1 and its interactions with
      substrates.
AB  - The human cytochrome P450 2W1 (CYP2W1) was categorized into the so-called
      "orphan" CYPs because of its unknown enzymatic function. However, recent studies
      showed that the recombinant CYP2W1 exhibited broad catalytic activity towards
      several chemicals. Furthermore, this enzyme was selectively expressed in some
      forms of cancers, whereas a very low expression was found in human normal issues.
      These render CYP2W1 as a potential drug target for cancer therapy. At present,
      however, little information is available on the active site topology and the
      substrate binding modes of CYP2W1. In this study, the three-dimensional model of
      CYP2W1 was constructed using the homology modeling method. Two known substrates,
      benzphetamine and indole, were then docked into the active site, and refined by
      molecular dynamics simulations. The interaction energy between the substrates and
      the enzyme was calculated and analyzed by using the MM-GBSA method. The results
      indicated that the constructed CYP2W1 model can account for the regioselectivity
      of this enzyme towards the known substrates and van der Waals interactions were
      the driving force for the substrate binding. Several key residues were identified
      to be responsible for the binding of indole and benzphetamine with CYP2W1. These
      findings provide useful information for the detailed characterization of the
      biological roles of CYP2W1 and structure-based drug design of this enzyme.

PMID- 19596604
TI  - Rigid gas permeable contact lenses: out in the cold.
AB  - INTRODUCTION: Rigid gas permeable (RGP) contact lens wearers may experience
      episodes of lens fracture during handling. In this paper, we report the case of a
      keratoconic contact lens wearer whose lens fractured whilst being handled at sub
      zero temperatures. Subsequent studies illustrate how PMMA and RGP contact lenses
      behave when exposed to sub-zero temperatures. METHODS: Using a previously
      validated custom-built strain gauge we have measured the force required to invert
      RGP contact lenses (Fluroperm, DK30-DK151, PMMA and Aquasil; dioptric power 
      2.00DS) under different temperature conditions. RESULTS: It was found that RGP
      lenses, frozen to -7 degrees C, required on average 15% less force to cause
      inversion than when stored at room temperature, regardless of material. It was
      also found that without due care, lenses of all materials fractured more easily
      after having been frozen, than lenses kept at room temperature. Fracture rates
      rose from 8% to 83% if lenses were stored wet (at -7 degrees C) as opposed to
      dry. CONCLUSION: The authors conclude that practitioners should consider
      inappropriate contact lens storage and handling as a possible reason for
      otherwise unexplained acute RGP contact lens fracture.

PMID- 19596605
TI  - Different melatonin rhythms and sleep-wake rhythms in patients on peritoneal
      dialysis, daytime hemodialysis and nocturnal hemodialysis.
AB  - BACKGROUND: Little comparative data on sleep-wake rhythms in different dialysis
      groups exist. The aim of this study was to investigate sleep-wake parameters
      measured with actigraphy and sleep questionnaires as well as melatonin rhythms in
      automated peritoneal dialysis, conventional daytime hemodialysis and nocturnal
      hemodialysis patients. METHODS: Conventional daytime dialysis (n=20), nocturnal
      hemodialysis (n=13) and automated peritoneal dialysis patients (n=6) were
      included in the study. Melatonin in saliva was sampled at 5 time points (21:00,
      23:00, 1:00, 7:00 and 9:00 h). Furthermore, actigraphy measurements and sleep
      questionnaires were performed. All parameters were tested by Kruskall-Wallis test
      (followed by post hoc Dunn test) to find significant differences (p<0.05).
      RESULTS: Although most sleep parameters were impaired in all three groups,
      conventional daytime dialysis patients had the worst sleep. In nocturnal
      hemodialysis patients a normal nocturnal melatonin rise was found. In daytime
      hemodialysis and automated peritoneal dialysis patients this rise was absent.
      CONCLUSIONS: The study showed impaired sleep parameters in all dialysis patient
      groups. As automated peritoneal dialysis is also performed during night time, the
      same effect on normalized melatonin was anticipated as was found in nocturnal
      hemodialysis. Melatonin seems to play a subordinate role in the sleep-wake rhythm
      of automated peritoneal dialysis patients.

PMID- 19596606
TI  - A case of resolution of amenorrhea after CPAP therapy for obstructive sleep
      apnea.

PMID- 19596607
TI  - Does the demand for asymmetric functional lower body postures in lateral sports
      relate to structural asymmetry of the pelvis?
AB  - Pelvic asymmetry has been thought to alter body mechanics and result in increased
      strain on bony and soft tissues possibly producing asymmetrical skeletal
      adaptations. The purpose of the present study was to determine if there is a
      greater prevalence of pelvic skeletal asymmetry in athletes who participate in a
      sport that requires a lateral dominance combined with increased spinal flexion
      and rotation. This is a descriptive laboratory study using a cross-sectional
      design. Sixty healthy female university age elite athletes and non-athletes
      participated in the study. The height and width of the anterior superior iliac
      spine (ASIS) and posterior superior iliac spine (PSIS) were measured using an
      electromagnetic tracking device with stylus. Using these measures a pelvic
      asymmetry ratio (PAR) was calculated for each athlete based on the difference in
      slope between the two ASIS and between the two PSIS. PAR was first assessed as a
      continuous variable to determine any differences in range of asymmetry between
      groups. All athletes were then assessed for prevalence of asymmetry as defined by
      a PAR score greater than 0.05. The results showed that there was a significant
      group effect in the magnitude and prevalence of asymmetry, with the lateral
      dominant group having significantly more of both. This study demonstrates that
      potentially there is an association between the asymmetrical nature of lateral
      dominant sports and pelvic skeletal asymmetry. However, there are possibly two
      confounding variables in age of initial participation and presence of low back
      pain that require further exploration.

PMID- 19596608
TI  - Inflammation and esophageal carcinogenesis.
AB  - The incidence of esophageal adenocarcinoma is increasing largely in Western
      populations, and patients diagnosed with this cancer continue to have a poor
      prognosis. The major risk factors are gastroesophageal reflux disease and
      Barrett's esophagus, both of which are associated with inflammation of the
      esophageal squamous epithelium, a condition called reflux esophagitis. The
      cellular mechanisms contributing to cancer development in the esophagus are
      poorly understood. The chronic inflammation that is present in Barrett's
      esophagus creates an environment suitable for DNA damage and altered expression
      of genes involved in cellular proliferation and inhibition of apoptosis. Key
      players in the inflammatory cascade include generation of free radicals,
      activation of kinases pathways and transcription factors, and production of
      cytokines and inflammatory enzymes. The current review highlights the link
      between reflux-induced inflammation and esophageal carcinogenesis. Understanding
      the molecular pathways involved in inflammation-associated esophageal
      tumorigenesis could enable the development of targeted therapies and offer a
      better therapeutic treatment in esophageal cancer.

PMID- 19596609
TI  - Long-term follow-up of male patients after reconstruction of the bladder
      exstrophy-epispadias complex: psychosocial status, continence, renal and genital
      function.
AB  - OBJECTIVE: There is a paucity of knowledge about long-term outcome issues in the
      bladder-exstrophy-epispadias complex (BEEC). Adult male BEEC patients were
      investigated in respect of bladder and renal function, fertility, genital
      function and psychosocial facts. PATIENTS AND METHODS: In a cross-sectional
      study, 17 adult male BEEC patients (mean age 23.4 years) from a single centre
      were evaluated with a questionnaire, renal and bladder ultrasound, blood tests,
      hormonal profile and semen analysis. RESULTS: Phenotypically one patient had
      complete epispadias and 16 had classical bladder exstrophy. Five patients
      underwent a one-stage functional reconstruction as a primary and 12 as a redo
      procedure. After a mean follow-up of 19.4 years, 15 bladders were preserved with
      12 voiding per urethram and 3 performing intermittent catheterization; 2 were
      secondarily diverted. Significant residual urine was present in 10; kidneys were
      normal in 14 patients. Sixteen patients proved ejaculations, 3 had normospermia,
      7 oligoasthenospermia and 6 azospermia. In patients with only one single bladder
      neck procedure normospermia was statistically significant. CONCLUSION: After
      functional BEEC reconstruction, long-term bladder function is preserved with
      mostly normal renal function. The number of bladder neck attempts has a
      significant influence on andrologic outcome. Detailed analysis may detect
      multifactorial pathogenesis from the impaired sperm quality in the BEEC.

PMID- 19596611
TI  - Urgent care in gynaecology: resuscitation and management of sepsis and acute
      blood loss.
AB  - Sepsis and/or acute blood loss can be encoutered as an emergency condition in
      gynaecology, especially in women with ectopic pregnancy/miscarriage, acute pelvic
      inflammatory disease (PID)/tuboovarian abscesses, post-puerperal
      sepsis/haemorrhage and even in postoperative scenarios. If underestimated or
      suboptimally treated, both can lead to an inadequate tissue perfusion (defined as
      shock) and the development of multi-organ failure. Morbidity and mortality after
      development of one of the shock syndromes (septic or haemorrhagic) correlates
      directly with the duration and severity of the malperfusion. The patient's
      prognosis depends on a prompt diagnosis of the presence of shock and immediate
      resuscitation to predefined physiological end-points, often before the cause of
      the shock has been identified. In septic shock, hypotension is primarily treated
      with fluid administration and eventually vasopressors, if required, in order to
      improve the circulation. Timely administration of antibiotics, control of
      infectious foci, appropriate use of corticoids and recombinant human activated
      protein C, tight glucose control, prophylaxis of deep vein thrombosis and stress
      ulcer prevention complete the therapy of septic shock. In haemorrhagic shock, the
      treatment primarily involves controlling haemorrhage, reversal of possible
      coagulopathy and administration of sufficient volumes of fluids and blood
      products to restore normal tissue perfusion.

PMID- 19596610
TI  - T cell receptor signaling induced by an analog peptide of type II collagen
      requires activation of Syk.
AB  - We have previously described an analog peptide of type II collagen (CII) that can
      suppress collagen-induced arthritis (CIA). This analog peptide represents CII(245
      270), the immunodominant epitope of CII, but with substitutions at 260, 261, and
      263 - CII(245-270) (A(260), B(261), and N(263)) (A9). To elucidate the mechanisms
      responsible for suppression, we used mice transgenic for a collagen-specific T
      cell receptor (TCR). When we found that APCs pulsed with A9 failed to induce T
      cell phosphorylation of TCR-zeta and ZAP-70, we explored alternative signaling
      pathways. We determined that A9 instead induced phosphorylation of spleen
      tyrosine kinase (Syk). The importance of Syk was confirmed by the use of chemical
      Syk inhibitors, which blocked both cytokine secretion and activation of GATA-3
      mediated by peptide A9. In summary, T cells use an alternative pathway in
      response to A9 that involves Syk. This novel T cell pathway may represent an
      important means for altering T cell phenotypes.

PMID- 19596612
TI  - Low frequency component in systolic arterial pressure variability in patients
      with persistent atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia characterized by irregular
      ventricular response. During AF, beat-to-beat variability of arterial pressure
      (AP) is increased because of continuous changes in filling time, stroke volume
      and contractility. Only a few studies have analyzed short-term AP variability
      during AF but they were mainly focused on the effects of respiration. We
      therefore analyzed short-term systolic (S), diastolic (D) and mean (M) AP
      variability by autoregressive method and an FFT-based spectral estimation (Welch
      periodogram) in 26 patients with persistent AF before and after restoration of
      sinus rhythm by electrical cardioversion. A low frequency (LF) component (central
      frequency 0.07+/-0.02 Hz, mean+/-standard deviation) of SAP variability was
      observed in 23 out of 26 patients during AF. Frequency analysis of DAP and MAP
      also showed a LF component with a central frequency of 0.08+/-0.03 Hz (20
      patients) and 0.07+/-0.03 Hz (25 patients), respectively. After recovery of sinus
      rhythm, we found significant reduction in mean SAP, DAP and MAP variability in
      all frequency bands. Squared coherence between SAP and heart rate variability
      after recovery of sinus rhythm revealed a weak and strong coupling within,
      respectively, LF and HF frequency bands. These data indicate that in patients
      with AF, in spite of an absence of rhythmical oscillation in RR interval time
      series, it is possible to observe a LF component in SAP, DAP and MAP variability
      signals. These 0.1 Hz fluctuations reflect the influence of the sympathetic
      fibres acting on the cardiovascular system.

PMID- 19596613
TI  - Localization of X-ray cross complementing gene 1 protein in the nuclear matrix is
      controlled by casein kinase II-dependent phosphorylation in response to oxidative
      damage.
AB  - Base excision repair/single strand break repair (BER/SSBR) of damaged DNA is a
      highly efficient process. X-ray cross complementing protein 1 (XRCC1) functions
      as a key scaffold protein for BER/SSBR factors. Recent work has shown that XRCC1
      forms dense foci at sites of DNA damage in a manner dependent on casein kinase II
      (CK2) phosphorylation. To investigate the mechanism underlying foci formation, we
      analyzed the subnuclear localization and phosphorylation status of XRCC1 during
      the repair process by biochemical fractionation of HeLa cellular proteins. The
      localization was also verified by in situ extraction of the fixed cells. In
      unchallenged cells, XRCC1 was primarily found in the chromatin fraction in a
      highly phosphorylated form; in addition, a minor population (10-15%) existed in
      the nuclear matrix (NM) with no or marginal phosphorylation. After hydrogen
      peroxide treatment, hyperphosphorylated XRCC1 appeared in the NM and accordingly,
      those in the chromatin fraction decreased. Foci formation and changes in XRCC1
      distribution could be abolished by the knockdown of CK2, the expression of a non
      phosphorylatable version of XRCC1, or the inhibition of poly-ADP ribosylation at
      the damage sites. Other BER factors, like DNA polymerase beta, were also found to
      accumulate in the NM after hydrogen peroxide-induced DNA damage, although its
      association with the NM seemed relatively weak. Our results suggest that the
      constitutive phosphorylation of XRCC1 in the chromatin and its DNA damage-induced
      recruitment to the NM are critical for foci formation, and that the core
      reactions of BER/SSBR may occur in the NM.

PMID- 19596614
TI  - Life at the top: the benefits of height.
AB  - According to the Gallup-Healthways Well-Being Index daily poll of the US
      population, taller people live better lives, at least on average. They evaluate
      their lives more favorably, and they are more likely to report a range of
      positive emotions such as enjoyment and happiness. They are also less likely to
      report a range of negative experiences, like sadness, and physical pain, though
      they are more likely to experience stress and anger, and if they are women, to
      worry. These findings cannot be attributed to different demographic or ethnic
      characteristics of taller people, but are almost entirely explained by the
      positive association between height and both income and education, both of which
      are positively linked to better lives.

PMID- 19596617
TI  - [Mesothelial giant cyst of great omentum].

PMID- 19596615
TI  - Endocytosis and signalling: a meeting with mathematics.
AB  - Although endocytosis has traditionally been understood as a signal attenuation
      mechanism, an emerging view considers endocytosis as an integral part of signal
      propagation and processing. On the short time scale, trafficking of endocytic
      vesicles contributes to signal propagation from the surface to distant targets,
      with bi-directional communication between signalling and trafficking.
      Mathematical modelling helps combine the mechanistic, molecular knowledge with
      rigorous analysis of the complex output dynamics of endocytosis in time and
      space. Simulations reveal novel roles for endocytosis, including the control of
      cell polarity, enhancing the spatial signal propagation, and controlling the
      signal magnitudes, kinetics, and synchronization with stimulus dynamics.

PMID- 19596616
TI  - A randomised study of hydro-jet vs. needle injection for lifting colorectal
      lesions prior to endoscopic resection.
AB  - BACKGROUND: Submucosal lifting of lesions prior to endoscopic resection is
      crucial to reduce complications and improve the technical feasibility of the
      procedure. AIM: To compare a self-assembled hydro-jet system vs. standard needle
      injection for tissue elevation prior to endoscopic resection of colorectal
      lesions. METHODS: Randomised study performed at a single tertiary care
      institution. Consecutive patients with colonoscopic diagnosis of sessile polyps
      or non-polypoid lesions >5 mm or laterally spreading tumours. OUTCOME MEASURES:
      successful elevation, time to proper elevation, completeness of excision, cautery
      damage, and general histological diagnostic quality (blinded pathologic
      assessment). RESULTS: 79 patients were randomised to hydro-jet (40 patients,
      group A) and needle (39 patients, group B) elevation. Successful elevation was
      achieved in 97.5% and 94.8%, respectively. Time to proper elevation was 8+/-5 s
      vs. 18+/-3 s (p<0.05). In group A, histology showed selective accumulation of
      fluid in the submucosa with intact collagen fibres. Damage to muscularis mucosa
      was never noted in the specimens of group A and in 7 cases of group B (p<0.01).
      Artefacts from "cautery effect" were very limited. Radial margins of resection
      could be adequately evaluated in all cases and were negative. CONCLUSIONS: The
      hydro-jet system is as effective and safe as standard needle injection for tissue
      elevation prior to endoscopic resection of colorectal lesions, but it is
      significantly faster.

PMID- 19596618
TI  - [Use of the rapid influenza virus antigen test in the paediatric population].

PMID- 19596619
TI  - [Preliminary clinical experience with PiCCO system in children with shock].
AB  - PURPOSE: To evaluate the PiCCO hemodynamics monitor in terms of clinical
      usefulness in children with shock. METHODS: Prospective multicenter analytical
      study in children aged from one month to 18 years with shock admitted to five
      pediatric intensive care units. Measurements were made before and after three
      interventions: a) volume load; b) increases in vasoactive drugs; c) dosage
      changes of drugs that could lessen vascular resistance. Recorded parameters
      included thermodilution data, along with the usual hemodynamic parameters.
      RESULTS: A total of 120 measurements were performed on 35 patients: mean age 36
      (2.6-156) months, mean weight 15 (5.8-72) kg. Shock etiology was septic in 37% of
      cases, cardiogenic in 26%, hypovolemic in 20% and neurogenic in 17%. No procedure
      related complication was noticed. Twenty-two volume challenges in 17 patients
      were registered. Volume load induced a significant intrathoracic blood volume
      index (ITBI) increase from 501(235-763) to 584 (418-810) ml/m(2), cardiac index
      (CI) 4.04 (2.58-6.25) to 4.48 (2.86-8.71) lmin-1m(2), and mean blood pressure
      from 74 (53-99) to 87 (59-112) mmHg. CI changes correlated with ITBI increase (r
      = 0.678, p = 0.001). 13 interventions to increase vasomotor tone were associated
      with an increase in contractility of 18% in systemic vascular resistance index
      (SVRI). CONCLUSIONS: Hemodynamic monitoring with the PiCCO system is feasible and
      seems safe in children with shock. PiCCO derived parameters could add clinically
      important information to assess preload state and its modifications with therapy.

PMID- 19596620
TI  - [Latin American network study of cardiorespiratory arrest in childhood].

PMID- 19596621
TI  - The relationship of hypercompetitiveness and gender roles with body dysmorphic
      disorder symptoms in a nonclinical sample.
AB  - This study examined whether hypercompetitiveness was a moderator between body
      dysmorphic disorder (BDD) symptoms and gender roles in 345 college students. To
      test this, the Body Dysmorphic Disorder Examination-Self Report (BDDE-SR), the
      Hypercompetitive Attitude Scale, and the Personal Attributes Questionnaire (PAQ)
      were used. Significant positive correlations were found between BDD symptoms and
      hypercompetitiveness in men and women. For men and women, no significant
      correlation was found between female-valued items on the PAQ and the BDDE-SR. A
      statistically significant negative correlation was found between male-valued
      items on the PAQ and the BDDE-SR for both genders. Hypercompetitiveness, however,
      was found not to be a moderator between BDD symptoms and gender roles.

PMID- 19596623
TI  - Malignant melanoma of the lower lip: case report.

PMID- 19596622
TI  - Orbital floor reconstruction: a case for silicone. A 12 year experience.
AB  - INTRODUCTION: Controversy still exists regarding the choice of implant material
      for orbital floor reconstructions, in particular the use of silicone. We aimed to
      evaluate the long-term outcomes of orbital floor reconstructions with silicone
      versus other non-silicone implants. PATIENTS AND METHODS: We conducted a 12 year
      retrospective review of patients who had orbital floor reconstructions for
      fractures at the Royal Hobart Hospital, Tasmania, Australia, from 1995 to 2007.
      Surgical admission notes, CT reports, operation records, outpatient notes, and
      complications were recorded. Long-term follow-up consisted of a structured
      telephone interview assessing patient outcomes and satisfaction, including
      ongoing disability, following orbital floor repair. RESULTS: Eighty one patients
      were identified as having had orbital floor reconstruction with an implant. Mean
      long-term follow-up was 63 months. Outcomes of Silicone implants (n=58) were
      compared to non-silicone implant materials (n=23) including titanium mesh,
      'Lactasorb', 'Resorb-X', autologous cartilage, and bone graft. Statistically
      significant advantages in the silicone group were found in the number of patients
      with palpable implants (24% vs 63%, p=0.005), the number of patients without any
      complaint (67% vs 32%, p=0.004), and the number of patients requiring subsequent
      surgery for complications related to their implants (5% vs 23%, p=0.046).
      CONCLUSION: The appropriate use of silicone implants for orbital floor
      reconstruction can have good results, contrary to much of the literature, with
      low complication rates including an acceptably low rate of infection and
      extrusion, as well as high patient satisfaction. To establish definite guidelines
      for best surgical practise, particularly amongst synthetic implant materials,
      prospective study is required.

PMID- 19596624
TI  - The 'round-the-clock' training model for assessment and warm up of microsurgical
      skills: a validation study.
AB  - Microsurgery is an essential technique in free flap reconstructions today. The
      technical skills involved require a learning curve, which may be affected by the
      current issues of limited training resources and patient safety. We describe a
      study on the value of a microsurgery training device as an assessment and warm up
      tool in basic microsurgery skills. Forty volunteers with different levels of
      microsurgery experience performed a microsurgical 'round-the-clock' exercise on
      the training device three consecutive times. Video-recordings of these
      performances were rated by two blinded independent assessors using a modified
      Global Rating Scale to assess basic microsurgery skills on the following
      parameters: steadiness, instruments handling and speed. Time to complete a round
      was also recorded objectively. The Kruskal-Wallis test was used to analyse the
      construct validity of the parameters assessed between the groups of level of
      microsurgery experience. Crohnbach's coefficient alpha was used to determine the
      reliability index of the independent assessors. All participants improved their
      time on consecutive rounds of the exercise. A median of 82 s (range 6-583 s)
      improvement in time between the first and third round was observed. Different
      mean performance time could be identified between the groups, but individual
      speed did not correlate significantly with microsurgery experience. Assessment of
      microsurgery skills using the modified Global Rating Scale demonstrated
      statistically significant differences for instruments handling (p=0.03) and speed
      (p=0.01) between the groups with regard to microsurgery experience, and
      improvement in the parameters assessed for all groups. Difference in steadiness
      (p=0.07) was not significant amongst the juniors. Consultants performed better
      than juniors but, at all levels of experience, significant improvement in skills
      was demonstrated after practice. The 'round-the-clock' microsurgery training
      device is an inexpensive and readily available valid tool that provides a useful
      warm up exercise and instant assessment of basic microsurgical skills.

PMID- 19596625
TI  - The 'criss-cross sling' modification of the vertical scar mastopexy.

PMID- 19596626
TI  - Aesthetic and functional reduction of the labia minora using the Maas and Hage
      technique.
AB  - INTRODUCTION: Enlarged labia minora can cause functional, aesthetic and
      psychosocial problems. There are many reported techniques for their surgical
      correction in both the gynaecological and surgical literature suggesting that no
      one method is superior to the others. The problem is compounded because an
      individual surgeon's experience is likely to be small given the infrequent
      request for surgery. For these reasons it is important that existing techniques
      are validated by independent surgeons rather than describing yet another
      variation. METHODS: Patients who underwent surgical reduction of their labia
      minora from 2001-2008 were retrospectively reviewed. All cases were performed by
      the same surgeon using the Maas and Hage technique of a running interdigitating W
      shaped excision. RESULTS: 12 patients aged from 15 to 52 years underwent
      reduction labioplasty for idiopathic hypertrophy. Postoperatively there were no
      wound dehiscences or infections. One patient developed a painful haematoma 2h
      after surgery necessitating surgical evacuation while another went into
      postoperative urinary retention relieved by overnight catheterisation. Both made
      uneventful recoveries. All patients were satisfied with their 'natural looking'
      cosmetic results and have returned to their normal activities without recurrence
      of their presenting symptoms. The mean follow up was 14 weeks but none have
      subsequently required or requested revisional surgery. CONCLUSIONS: The running W
      shaped resection was found to be an easy and effective method of reducing the
      labia minora by a single operator in a small series of cases. This independent
      review demonstrates the reproducibility of this technique and the favourable
      aesthetic and functional outcomes for the patient.

PMID- 19596627
TI  - Purple glove syndrome: a case report. Hand surgeons and physicians be aware.

PMID- 19596628
TI  - Bonding agents of low fusing cpTi porcelains: elemental and morphological
      characterization.
AB  - Low fusing porcelains demonstrate great variations in bond strength with cpTi, a
      result directly associated with the performance of their bonding agents. The aim
      of this study was to investigate the composition of bonding agents used for the
      production of Ti-ceramic restorations. The powder or paste components of nine
      commercially available products were imaged under LV-SEM and their elemental
      composition was determined by energy-dispersive X-ray microanalysis (X-ray EDS).
      According to the EDS results five bonding agents (Duceratin, Duceratin Plus, Ti
      22, TitanKeramik, and Triceram) were mainly composed of Si Sn and Na oxides.
      TiKrom contained La and Ba, whereas Initial Ti was based on La, B, and Sr
      formulations. Backscattered electron images revealed that Titankeramik, Triceram
      paste, Initial Bonder and Aesthetic Universal Bonder consisted of a single-phase
      material, while Duceratin, Duceratin Plus, Ti-22, Tikrom, and Triceram powders
      consisted of two-phase materials. The large differences found in elemental
      compositions of the bonding agents and the development of completely new
      formulations imply that the relevant technology has not yet attained a standard
      and thus is a promising field for further research.

PMID- 19596630
TI  - Identification of faecal transmission of Toxoplasma gondii: Small science, large
      characters.
AB  - The first clue to the elucidation of the complete life cycle of Toxoplasma gondii
      was the identification of an infectious form in cat faeces that could be
      transmitted orally and could survive in the external environment for extended
      periods. This personal review describes the scientist (W.M. Hutchison) and the
      background to the initial discovery and covers the period to the complete
      elucidation of the life cycle of T. gondii.

PMID- 19596632
TI  - Error minimized extreme learning machine with growth of hidden nodes and
      incremental learning.
AB  - One of the open problems in neural network research is how to automatically
      determine network architectures for given applications. In this brief, we propose
      a simple and efficient approach to automatically determine the number of hidden
      nodes in generalized single-hidden-layer feedforward networks (SLFNs) which need
      not be neural alike. This approach referred to as error minimized extreme
      learning machine (EM-ELM) can add random hidden nodes to SLFNs one by one or
      group by group (with varying group size). During the growth of the networks, the
      output weights are updated incrementally. The convergence of this approach is
      proved in this brief as well. Simulation results demonstrate and verify that our
      new approach is much faster than other sequential/incremental/growing algorithms
      with good generalization performance.

PMID- 19596631
TI  - Simple artificial neural networks that match probability and exploit and explore
      when confronting a multiarmed bandit.
AB  - The matching law (Herrnstein 1961) states that response rates become proportional
      to reinforcement rates; this is related to the empirical phenomenon called
      probability matching (Vulkan 2000). Here, we show that a simple artificial neural
      network generates responses consistent with probability matching. This behavior
      was then used to create an operant procedure for network learning. We use the
      multiarmed bandit (Gittins 1989), a classic problem of choice behavior, to
      illustrate that operant training balances exploiting the bandit arm expected to
      pay off most frequently with exploring other arms. Perceptrons provide a medium
      for relating results from neural networks, genetic algorithms, animal learning,
      contingency theory, reinforcement learning, and theories of choice.

PMID- 19596633
TI  - Model selection criteria for image restoration.
AB  - In this brief, the image restoration problem is approached as a learning system
      problem, in which a model is to be selected and parameters are estimated.
      Although the parameters which correspond to the restored image can easily be
      obtained, their quality depend heavily on a proper choice of the regularization
      parameter that controls the tradeoff between fidelity to the blurred noisy
      observed image and the smoothness of the restored image. By analogy between the
      model selection philosophy that constitutes a fundamental task in systems
      learning and the choice of the regularization parameter, two criteria are
      proposed in this brief for selecting the regularization parameter. These criteria
      are based on Bayesian arguments and the Kullback-Leibler divergence and they can
      be considered as extensions of the Bayesian information criterion (BIC) and the
      Akaike information criterion (AIC) for the image restoration problem.

PMID- 19596634
TI  - Asymptotic tracking of uncertain systems with continuous control using adaptive
      bounding.
AB  - This paper presents a robust adaptive control design method for a class of
      multiple-input-multiple-output uncertain nonlinear systems in the presence of
      parametric and nonparametric uncertainties and bounded disturbances. Using the
      approximation properties of the unknown continuous nonlinearities and the
      adaptive bounding technique, the developed controller achieves asymptotic
      convergence of the tracking error to zero, while ensuring boundedness of
      parameter estimation errors. The algorithm does not assume the knowledge of any
      bound on the unknown quantities in designing the controller. It is based on an
      integral technique involving the filtered tracking error and produces a
      continuous control. Theoretical developments are illustrated via simulation
      results.

PMID- 19596636
TI  - Maximum likelihood blind image separation using nonsymmetrical half-plane Markov
      random fields.
AB  - This paper presents a maximum likelihood approach for blindly separating linear
      instantaneous mixtures of images. The spatial autocorrelation within each image
      is described using nonsymmetrical half-plane (NSHP) Markov random fields in order
      to simplify the joint probability density functions of the source images. A first
      implementation assuming stationary sources is presented. It is then extended to a
      more realistic nonstationary image model: two approaches, respectively based on
      blocking and kernel smoothing, are proposed to cope with the nonstationarity of
      the images. The estimation of the mixing matrix is performed using an iterative
      equivariant version of the Newton-Raphson algorithm. Moreover, score functions,
      required for the computation of the updating rule, are approximated at each
      iteration by parametric polynomial estimators. Results achieved with artificial
      mixtures of both artificial and real-world images, including an astrophysical
      application, clearly prove the high performance of our methods, as compared to
      classical algorithms.

PMID- 19596635
TI  - BAM learning of nonlinearly separable tasks by using an asymmetrical output
      function and reinforcement learning.
AB  - Most bidirectional associative memory (BAM) networks use a symmetrical output
      function for dual fixed-point behavior. In this paper, we show that by
      introducing an asymmetry parameter into a recently introduced chaotic BAM output
      function, prior knowledge can be used to momentarily disable desired attractors
      from memory, hence biasing the search space to improve recall performance. This
      property allows control of chaotic wandering, favoring given subspaces over
      others. In addition, reinforcement learning can then enable a dual BAM
      architecture to store and recall nonlinearly separable patterns. Our results
      allow the same BAM framework to model three different types of learning:
      supervised, reinforcement, and unsupervised. This ability is very promising from
      the cognitive modeling viewpoint. The new BAM model is also useful from an
      engineering perspective; our simulations results reveal a notable overall
      increase in BAM learning and recall performances when using a hybrid model with
      the general regression neural network (GRNN).

PMID- 19596637
TI  - Natural and seamless image composition with color control.
AB  - While the state-of-the-art image composition algorithms subtly handle the object
      boundary to achieve seamless image copy-and-paste, it is observed that they are
      unable to preserve the color fidelity of the source object, often require quite
      an amount of user interactions, and often fail to achieve realism when there
      exists salient discrepancy between the background textures in the source and
      destination images. These observations motivate our research towards color
      controlled natural and seamless image composition with least user interactions.
      In particular, based on the Poisson image editing framework, we first propose a
      variational model that considers both the gradient constraint and the color
      fidelity. The proposed model allows users to control the coloring effect caused
      by gradient domain fusion. Second, to have less user interactions, we propose a
      distance-enhanced random walks algorithm, through which we avoid the necessity of
      accurate image segmentation while still able to highlight the foreground object.
      Third, we propose a multiresolution framework to perform image compositions at
      different subbands so as to separate the texture and color components to
      simultaneously achieve smooth texture transition and desired color control. The
      experimental results demonstrate that our proposed framework achieves better and
      more realistic results for images with salient background color or texture
      differences, while providing comparable results as the state-of-the-art
      algorithms for images without the need of preserving the object color fidelity
      and without significant background texture discrepancy.

PMID- 19596638
TI  - Morphological description of color images for content-based image retrieval.
AB  - Placed within the context of content-based image retrieval, we study in this
      paper the potential of morphological operators as far as color description is
      concerned, a booming field to which the morphological framework, however, has
      only recently started to be applied. More precisely, we present three morphology
      based approaches, one making use of granulometries independently computed for
      each subquantized color and two employing the principle of multiresolution
      histograms for describing color, using respectively morphological levelings and
      watersheds. These new morphological color descriptors are subsequently compared
      against known alternatives in a series of experiments, the results of which
      assert the practical interest of the proposed methods.

PMID- 19596639
TI  - Face recognition using dual-tree complex wavelet features.
AB  - We propose a novel facial representation based on the dual-tree complex wavelet
      transform for face recognition. It is effective and efficient to represent the
      geometrical structures in facial image with low redundancy. Moreover, we
      experimentally verify that the proposed method is more powerful to extract facial
      features robust against the variations of shift and illumination than the
      discrete wavelet transform and Gabor wavelet transform.

PMID- 19596640
TI  - Retrieval efficiency of DNA-based databases of digital signals.
AB  - Using DNA to store digital signals, or data in general, offers significant
      advantages when compared to other media. The DNA molecule, especially in its
      double-stranded form, is very stable, compact, and inexpensive. In the past, we
      have shown that DNA can be used to store and retrieve digital signals encoded and
      stored in DNA. We have also shown that DNA hybridization can be used as a
      similarity criterion for retrieving digital signals encoded and stored in a DNA
      database. Retrieval is achieved through hybridization of "query" and "data" DNA
      molecules. In this paper, we present a mathematical framework to simulate single
      query and parallel-query scenarios, and to estimate hybridization efficiency. Our
      framework allows for exact numerical solutions as well as closed-form
      approximations under certain conditions. Similarly to the digital domain, we
      define a DNA SNR measure to assess the performance of the DNA-based retrieval
      scheme in terms of database size and source statistics. With approximations, we
      show that the SNR of any finite-sized DNA-based database is upper bounded by the
      SNR of an infinitely large DNA-based database that has the same source
      distribution. Computer simulations are presented to validate our results.

PMID- 19596641
TI  - Guttate morphea in a scleroderma spectrum disorder patient with anticentromere
      antibody.

PMID- 19596644
TI  - Evolving approaches to metastatic breast cancer previously treated with
      anthracyclines and taxanes.
AB  - Despite major advances in the adjuvant treatment of breast cancer, many women
      will develop metastatic disease, either de novo or following optimal adjuvant
      therapy. Further effective therapeutic options are needed for women who progress
      following anthracycline- and taxane-containing regimens. Capecitabine is approved
      by the US Food and Drug Administration as monotherapy in this setting. Other
      agents such as gemcitabine or vinorelbine might be considered based on multiple
      phase II studies. Combination therapies generally increase response rates but
      with a concomitant increase in toxicity. Other agents that have been studied in
      this setting include etoposide, irinotecan, and pemetrexed. Novel agents
      undergoing testing include the fluorinated vinca alkaloid vinflunine and the
      halichondrin B analogue eribulin. Responses have been seen in taxane-pretreated
      patients with the use of another conventional taxane, novel formulations, or
      alternative schedules. Pegylated liposomal doxorubicin might be considered in
      some patients for whom there is a concern regarding cardiac toxicity with the
      conventional preparation. The epothilones are a novel group of microtubule
      stabilizing agents. Ixabepilone is a member of this class that has been approved
      as monotherapy in patients whose tumors are resistant or refractory to
      anthracyclines, taxanes, and capecitabine. It is also approved with capecitabine
      in patients whose cancer is resistant to treatment with anthracyclines and
      taxanes. Decision-making regarding treatment selection must take into account
      multiple patient and tumor factors. The therapeutic indices of the available
      treatments should be considered in the context of the individual patient.

PMID- 19596645
TI  - First-line chemotherapy for metastatic breast cancer.
AB  - The selection of first-line chemotherapy for metastatic breast cancer (MBC) is
      complex because of the myriad of treatment options available and the inherent
      biologic heterogeneity of the disease. The potential treatment options are
      greatly influenced by estrogen and progesterone receptor and HER2 status of the
      tumor, and biopsy with reassessment of these markers at the time of disease
      recurrence is strongly recommended. Metastatic breast cancer is generally an
      incurable disease, with survival that could range from months to several years.
      Important but modest improvements in overall survival (OS) have been observed for
      women with MBC over the past few decades, in part because of improvements in
      systemic therapy. For women with endocrine-responsive disease, hormonal therapy
      is the appropriate initial treatment choice at the time of disease recurrence
      with rare exception. Initiation of systemic chemotherapy is appropriate for women
      with disease that is either hormone receptor negative, endocrine therapy
      refractory, or rapidly progressive with visceral involvement. The addition of
      trastuzumab to chemotherapy for women with HER2-positive breast cancer represents
      a clear standard of care. For HER2-negative MBC, sequential single-agent
      chemotherapy is preferred over combination therapy as a result of the more
      favorable toxicity profile and absence of a clinically significant improvement in
      survival with combination treatment. Many single-agent chemotherapeutic agents
      have activity in MBC, with most data supporting an anthracycline- or taxane-based
      approach. Bevacizumab in combination with chemotherapy prolongs progression-free
      survival in women with MBC, though its position in the first-line treatment of
      MBC relative to standard chemotherapy remains unclear at this time because of
      lack of OS benefit.

PMID- 19596643
TI  - Treatment of HER2-positive metastatic breast cancer following initial
      progression.
AB  - Significant advances in molecular-targeted therapies have provided more effective
      and less aggressive forms of therapy for patients with HER2-overexpressing
      metastatic breast cancers. Despite the initial encouraging results of many
      therapeutic randomized trials that have been undertaken in this setting, de novo
      and acquired resistance to trastuzumab, the first anti-HER2 monoclonal antibody
      to demonstrate significant activity in this setting, can occur. Because recent
      studies strongly support a role for trastuzumab in not only the management of
      metastatic disease but also the adjuvant setting for HER2-overexpressing breast
      cancers, the clinical problem of trastuzumab resistance is becoming increasingly
      important. Specific recommendations for the optimal treatment of HER2
      overexpressing metastatic disease are challenging because considerable advances
      in the field have been made. This article will review some of the main points to
      be considered for decision-making in anti-HER2 treatment in the metastatic
      setting: (1) the benefit of continued trastuzumab after progression on a first
      line trastuzumab-containing regimen, (2) novel agents that have been recently
      added to the plethora of drugs available to treat HER2-overexpressing breast
      cancers, and (3) molecular mechanisms that contribute to trastuzumab resistance.
      These issues are imperative in identifying novel therapeutic targets with the
      goal of increasing the magnitude and duration of response to trastuzumab-based
      treatment.

PMID- 19596646
TI  - Biology, metastatic patterns, and treatment of patients with triple-negative
      breast cancer.
AB  - Of the estimated 1 million cases of breast cancer diagnosed annually worldwide,
      it is estimated that over 170,000 will harbor the triple-negative (estrogen
      receptor/progesterone receptor/HER2-negative) phenotype. Most, though not all,
      triple-negative breast cancers will be basal-like on gene expression micorarrays.
      The basal-like molecular subtype exhibits a unique molecular profile and set of
      risk factors, aggressive and early pattern of metastasis, limited treatment
      options, and poor prognosis. Large population-based studies have identified a
      higher proportion of triple-negative breast tumors among premenopausal African
      American women, and a suggestion that increased parity, younger age at first-term
      pregnancy, shorter duration of breast feeding, and elevated hip-to-waist ratio
      might be particular risk factors. When BRCA1 mutation carriers develop breast
      cancer, it is usually basal-like; given the central role of BRCA1 in DNA repair,
      this could have profound therapeutic implications. When diagnosed, triple
      negative breast cancers illustrate preferential relapse in visceral organs,
      including the central nervous system. Although initial response to chemotherapy
      might be more profound, relapse is early and common among triple-negative breast
      cancers compared with luminal breast cancers. The armamentarium of "targeted
      therapeutics" for triple-negative breast cancer is evolving and includes
      strategies to inhibit angiogenesis, epidermal growth factor receptor, and other
      kinases. Finally, the positive association between triple-negative breast cancer
      and BRCA mutations makes inhibition of poly(adenosine diphosphate-ribose)
      polymerase-1 an attractive therapeutic strategy that is in active study.

PMID- 19596649
TI  - Bone Health and Falls: Fracture Risk in Breast Cancer Survivors With Chemotherapy
      Induced Amenorrhea.
AB  - Purpose/Objectives: To describe risk factors for fracture-bone health and falls
      among breast cancer survivors with chemotherapy-induced amenorrhea.Design: Cross
      sectional and prospective cohort.Setting: National Cancer Institute-designated
      cancer center in the Pacific northwest region of the United States.Sample: Breast
      cancer survivors with chemotherapy-induced amenorrhea (N = 35; X age = 46 years;
      one year after chemotherapy) compared to cancer-free controls (N = 26; X age = 41
      years).Methods: One two-hour testing session at baseline, 12-month follow-up,
      monthly postcards.Main Research Variables: Clinical characteristics and number of
      falls, leg strength, bone mineral density (BMD), body composition, and bone
      turnover.Findings: No significant differences between groups for BMD at either
      time point. Significantly more breast cancer survivors had low-spine BMD based on
      T scores and elevated bone turnover versus controls at baseline and follow-up.
      Breast cancer survivors with low-spine BMD have significantly lower body mass
      index, lean mass, and leg strength, and had stage II disease more often than
      breast cancer survivors with normal BMD. Significantly more breast cancer
      survivors (75%) experienced at least one fall compared to 46% of controls. Among
      breast cancer survivors, those who had fallen had significantly lower leg
      strength and calcium intakes than those who had not.Conclusions: Breast cancer
      survivors with chemotherapy-induced amenorrhea, particularly those with muscle
      weakness, may be at increased risk of fracture.Implications for Nursing: Breast
      cancer survivors with chemotherapy-induced amenorrhea should be evaluated for low
      bone mass and fall risk and considered for therapeutic intervention to lower
      fracture risk.

PMID- 19596650
TI  - Cognitive Dysfunction and Its Relationship to Quality of Life in Breast Cancer
      Survivors.
AB  - Purpose/Objectives: To examine relationships between capacity to direct attention
      and the quality-of-life (QOL) domains of psychological and physical well-being in
      breast cancer survivors.Design: Descriptive, correlational.Setting: National
      Cancer Institute-designated oncology and county hospital outpatient clinics in
      the midwestern region of the United States.Sample: 134 breast cancer survivors
      aged 32-79 years (X = 56.3, SD = 9.4) with a mean of 6.4 years since diagnosis
      (SD = 2.8, range = 1-10).Methods: Secondary analysis of questionnaire data
      measuring cognitive dysfunction and two QOL domains. Descriptive statistics,
      Pearson or Spearman correlations, and multiple regression analysis were used.Main
      Research Variables: Capacity to direct attention, as well as psychological and
      physical well-being.Findings: Deficits in capacity to direct attention were
      related to poorer QOL, including more depressive symptoms, lower well-being,
      poorer physical functioning, and greater fatigue.Conclusions: Capacity to direct
      attention was related to psychological and physical well-being in breast cancer
      survivors.Implications for Nursing: Nurses are in a prime position to assess
      breast cancer survivors' capacity to direct attention and resulting relationships
      with QOL. Findings suggest that nursing interventions that address survivors'
      capacity to direct attention may have a broad impact on QOL.

PMID- 19596652
TI  - Efficacy of Crude Marijuana and Synthetic Delta-9-Tetrahydrocannabinol as
      Treatment for Chemotherapy-Induced Nausea and Vomiting: A Systematic Literature
      Review.
AB  - Purpose/Objectives: To synthesize the research to determine whether oral delta-9
      tetrahydrocannabinol (THC) and smoked marijuana are effective treatments for
      chemotherapy-induced nausea and vomiting (CINV) and to evaluate side effects and
      patient preference of these treatments.Data Sources: Original research, review
      articles, and other published articles in CINAHL(R), MEDLINE(R), and Cochrane
      Library databases.Data Synthesis: Cannabinoids are effective in controlling CINV,
      and oral THC and smoked marijuana have similar efficacy. However, smoked
      marijuana may not be accessible or safe for all patients with cancer. Also, these
      drugs have a unique side-effect profile that may include alterations in motor
      control, dizziness, dysphoria, and decreased concentration.Conclusions: This
      synthesis shows that cannabinoids are more effective than placebo and comparable
      to antiemetics such as prochlorperazine and ondansetron for CINV.Implications for
      Nursing: Nurses should feel supported by the literature to recommend oral
      synthetic THC as a treatment for CINV to their patients and physician colleagues.
      Nurses should be cognizant of the side-effect profile for this medication and
      provide appropriate patient education.

PMID- 19596651
TI  - Determinants of Mammography Screening Participation in Adult Childhood Cancer
      Survivors: Results From the Childhood Cancer Survivor Study.
AB  - Purpose/Objectives: To identify treatment, intrapersonal, and provider factors
      that influence childhood cancer survivors' adherence to recommended mammography
      screening.Design: Secondary analysis of data derived from three consecutive
      surveys within the Childhood Cancer Survivor Study.Sample: Female childhood
      cancer survivors: N = 335, X age = 30.92, X years after diagnosis =
      21.79.Methods: T tests and structural equation modeling.Main Research Variables:
      Mammogram recency, health concerns, affect, motivation, and survivor-provider
      interaction.Findings: Forty-three percent of the variance was explained in
      mammogram recency. Survivors most likely to follow the recommended mammogram
      schedule were directly influenced by cancer treatment exposure to mantle
      radiation (p = 0.01), less intrinsic motivation (p = 0.01), positive affect (p =
      0.05), recent visits to an oncology clinic (p = 0.01), discussion of subsequent
      cancer risks with a physician (p = 0.001), perceptions of more severe late
      effects (p = 0.05), age (40 years or older) (p </= 0.001), and a print media
      intervention detailing breast cancer risks and follow-up strategies.Conclusions:
      Perceived symptoms, motivation, affect, provider influences, readiness for
      medical follow-up, and knowledge of treatment exposures are potential modifiable
      targets for intervention to support mammography screening in childhood cancer
      survivors at risk.Implications for Nursing: (a) Provide written summaries of
      treatment exposures and recommended schedule of mammography screening at the end
      of cancer treatment and throughout follow-up; (b) identify and address survivor
      symptoms and concerns that may negate screening; and (c) enhance motivation for
      screening by tailoring personal risk information to health concerns, affect, and
      readiness for follow-up.

PMID- 19596653
TI  - Fatalism and Mammography in a Multicultural Population.
AB  - Purpose/Objectives: To assess levels of fatalistic beliefs and their association
      with mammography use in four population groups in Israel.Design: Telephone
      survey.Setting: Maccabi Healthcare Services in Israel.Sample: A random sample of
      1,550 Arabic and Jewish women.Methods: A random telephone survey was performed
      during May and June 2007. Women's fatalistic beliefs were measured. Information
      from claims records regarding mammography use was obtained for each woman.Main
      Research Variables: Levels of fatalistic beliefs and mammography use.Findings:
      Fatalistic beliefs included general beliefs that God or fate (external force) was
      the cause of cancer and related to cancer survivorship. The higher-educated women
      reported less fatalistic beliefs. Arab women reported more fatalistic beliefs
      compared to the other women. Mammography use was associated with fatalistic
      beliefs that external forces were the cause of cancer among Arab and immigrant
      women but not among veteran Jewish and ultraorthodox women. Fatalistic beliefs
      about cancer survivorship were not associated with mammography in any of the
      population groups. Levels of fatalism and education may explain the difference in
      rates of mammography among Arab and Jewish women.Conclusions: High levels of
      fatalism may inhibit women from having a mammogram, particularly Arab and
      immigrant women in Israel. However, this is not a generalizable result for all
      population groups and all types of fatalism.Implications for Nursing:
      Interventions to decrease fatalism in Arabs and immigrants may increase
      compliance with mammography. Nurses may achieve this by developing tailored
      messages for women who believe that external forces are the cause of cancer.

PMID- 19596657
TI  - Promoting employee wellbeing: the relevance of work characteristics and
      organizational justice.
AB  - Research focusing on the relationship between organizational justice and health
      suggests that perceptions of fairness can make significant contributions to
      employee wellbeing. However, studies examining the justice-health relationship
      are only just emerging and there are several areas where further research is
      required, in particular, the uniqueness of the contributions made by justice and
      the extent to which the health effects can be explained by linear, non-linear
      and/or interaction models. The primary aim of the current study was to determine
      the main, curvilinear and interaction effects of work characteristics and
      organizational justice perceptions on employee wellbeing (as measured by
      psychological health and job satisfaction). Work characteristics were measured
      using the demand-control-support (DCS) model (Karasek and Theorell, 1990) and
      Colquitt's (2001) four justice dimensions (distributive, procedural,
      interpersonal and informational) assessed organizational justice (Colquitt,
      2001). Hierarchical regression analyses found that in relation to psychological
      health, perceptions of justice added little to the explanatory power of the DCS
      model. In contrast, organizational justice did account for unique variance in job
      satisfaction, the second measure of employee wellbeing. The results supported
      linear relationships between the psychosocial working conditions and the outcome
      measures. A significant two-way interaction effect (control x support at work)
      was found for the psychological health outcome and the procedural justice by
      distributive justice interaction was significant for the job satisfaction
      outcome. Notably, the findings indicate that in addition to traditional job
      stressors, health promotion strategies should also address organizational
      justice.

PMID- 19596656
TI  - Nuclear receptor-coregulator interaction profiling identifies TRIP3 as a novel
      peroxisome proliferator-activated receptor gamma cofactor.
AB  - Nuclear receptors (NRs) are major targets for drug discovery and have key roles
      in development and homeostasis as well as in many diseases such as obesity,
      diabetes, and cancer. NRs are ligand-dependent transcription factors that need to
      work in concert with so-called transcriptional coregulators, including
      corepressors and coactivators, to regulate transcription. Upon ligand binding,
      NRs undergo a conformational change, which alters their binding preference for
      coregulators. Short alpha-helical sequences in the coregulator proteins, LXXLL
      (in coactivators) or LXXXIXXXL (in corepressors), are essential for the NR
      coregulator interactions. However, little is known on how specificity is
      dictated. To obtain a comprehensive overview of NR-coregulator interactions, we
      used a microarray approach based on interactions between NRs and peptides derived
      from known coregulators. Using the peroxisome proliferator-activated receptor
      gamma (PPARgamma) as a model NR, we were able to generate ligand-specific
      interaction profiles (agonist rosiglitazone versus antagonist GW9662 versus
      selective PPARgamma modulator telmisartan) and characterize NR mutants and
      isotypes (PPARalpha, -beta/delta, and -gamma). Importantly, based on the NR
      coregulator interaction profile, we were able to identify TRIP3 as a novel
      regulator of PPARgamma-mediated adipocyte differentiation. These findings
      indicate that NR-coregulator interaction profiling may be a useful tool for drug
      development and biological discovery.

PMID- 19596659
TI  - Transfusion and mortality in patients with ST-segment elevation myocardial
      infarction treated with primary percutaneous coronary intervention.
AB  - AIMS: Red blood cell transfusion is associated with increased mortality among
      patients with acute coronary syndromes, but little is known about the
      consequences of transfusion in a contemporary setting of ST-segment elevation
      myocardial infarction. We describe the association between transfusion and 90-day
      mortality among patients with acute myocardial infarction treated with primary
      percutaneous coronary intervention. METHODS AND RESULTS: Analyses were performed
      on 5532 patients with ST-elevation myocardial infarction from the Assessment of
      Pexelizumab in Acute Myocardial Infarction trial. The primary objective of this
      analysis was to ascertain the relation between red blood cell transfusion and 90
      day mortality in patients with recent myocardial infarction. We initially
      determined the baseline and in-hospital predictors of transfusion (multivariable
      logistic regressions) and subsequently assessed the association between
      transfusion and mortality using a series of Cox proportional hazards regression
      combined to a landmark analyses. A total of 213 patients (3.9%) received a
      transfusion. Transfusion remained significantly associated with mortality
      [hazards ratio = 2.16 (1.20-3.88)], despite adjustment for baseline
      characteristics, in-hospital co-interventions, and for propensity of receiving a
      transfusion. Among patients who survived to hospital discharge, however, the
      hazard of death was not different in patients treated with transfusion.
      CONCLUSION: Transfusion is associated with 90-day mortality in acute myocardial
      infarction treated with primary percutaneous coronary intervention. Although
      transfusion may be causally related to mortality, it is likely that at least part
      of the association is due to confounding. This association illustrates the
      complex relationship between transfusion, bleeding, and mortality and underscores
      the need for further research to understand the relationship between transfusion
      and clinical outcomes.

PMID- 19596658
TI  - Stent thrombosis after drug-eluting stent implantation: incidence, timing, and
      relation to discontinuation of clopidogrel therapy over a 4-year period.
AB  - AIMS: To assess the incidence, timing, and relation of drug-eluting stent (DES)
      thrombosis to discontinuation of clopidogrel therapy. METHODS AND RESULTS: This
      prospective observational cohort study included 6816 consecutive patients that
      underwent successful DES implantation. Primary endpoint was definite stent
      thrombosis (ST). During 4 years of follow-up, definite ST was observed in 73
      patients, corresponding to a cumulative incidence of 1.2%. Cumulative incidence
      of ST at 30 days was 0.5 and 0.8% at 1 year, respectively. Discontinuation of
      clopidogrel therapy was significantly associated with ST only in the first 6
      months after the procedure (P < 0.001). During that period, the median time
      interval from clopidogrel discontinuation to ST was 9 days [interquartile range
      (IQR) 5.5-22.5] while thereafter it was 104.3 days (IQR 7.4-294.8). CONCLUSION:
      The 4 year incidence of ST after DES implantation is low. A relevant number of ST
      occur early after discontinuation of clopidogrel therapy. The dependence of ST on
      discontinuation of clopidogrel therapy seems to be mostly confined to the first 6
      months after DES implantation. However, specifically designed randomized studies
      are required to establish the optimal length of clopidogrel therapy after DES
      implantation.

PMID- 19596660
TI  - Acute proximal LAD occlusion without ST-segment elevation.

PMID- 19596661
TI  - Left atrial size: a structural expression of abnormal left ventricular segmental
      relaxation evaluated by strain echocardiography.
AB  - AIMS: Left atrial (LA) enlargement is related to left ventricular (LV)
      remodelling and diastolic dysfunction (DD), reflecting cardiac target organ
      damage. The aim of this study was to investigate the relation of one-dimensional
      (1D) and volume derived indexes of LA enlargement with abnormal segmental
      relaxation in hypertensive patients. METHODS AND RESULTS: We evaluated 90
      hypertensive patients and 50 non-hypertensive volunteers with normal ejection
      fraction (EF). Global DD was evaluated based on conventional indexes (E/A,
      deceleration time, LV isovolumic relaxation time), and segmental early and late
      diastolic strain rates (SR) were recorded from 18 LV segments. The number of
      segments with abnormal relaxation (SR(E)/SR(A) < 1.1) was represented as
      segmental DD. LA size was evaluated based on 1D left atrial dimension (LAD) and
      left atrial volume (LAV), and indexed by body surface area (BSA) and height. The
      hypertensive patients had higher segmental DD (9.5 +/- 4.2 vs. 5.2 +/- 3.2, P <
      0.05) and appeared to have higher 1D and volume-derived indexes of LA size
      compared to the controls. Individuals with global DD had more deteriorated
      segmental relaxation and higher LA size compared with those without global DD.
      When participants were separated according to normal, mildly dilated, and
      moderately to severely dilated LA size, there was progressive deterioration of
      segmental DD, mean Ea, and filling pressures, along with the progression of LA
      enlargement. Volume-derived indexes, LAV/BSA, LAV/height, and LAV, appeared to
      have better correlations with segmental DD, as well as with linearly changed
      parameters of DD (Mean Ea, E/Ea), LV remodelling (LVMI, relative wall thickness),
      age, and systolic blood pressure (SBP), compared to the respective 1D-based (LAD)
      LA indexes. LAV/BSA was proved to be an independent predictor of segmental DD
      (beta: 0.23, R(2): 0.48), along with LVMI, SBP and age, irrespective of gender.
      CONCLUSION: LA size constitutes a morphological expression of abnormal segmental
      relaxation, with volume-derived indexes of LA enlargement, exhibiting higher
      correlation with segmental DD compared to the respective 1D indexes, and LAV/BSA
      to be an independent predictor of segmental DD in hypertensive heart disease.

PMID- 19596662
TI  - Elevating blood pressure as a strategy to increase tumor-targeted delivery of
      macromolecular drug SMANCS: cases of advanced solid tumors.
AB  - The purpose of this study is to evaluate the improved method of arterial infusion
      therapy of SMANCS (SX) with lipiodol under the angiotensin-induced hypertensive
      state for various difficult-to-treat solid tumors. Most patients were
      unresectable with no other therapeutic options, recurrence after resection, or
      patients do not respond to common treatments. The new method utilizes angiotensin
      II (AT) to induce hypertension (e.g. approximately 15-30 mmHg above norm) for 15
      20 min. This method was successfully applied to metastatic liver cancer,
      cholangiocarcinoma, massive renal cell carcinoma, pancreatic and other abdominal
      solid cancers. This AT-induced hypertension resulted in remarkably enhanced tumor
      delivery accompanied by improved therapeutic response, and a shorter time to
      achieve 50% regression of tumor size with least toxicity. We demonstrated
      clinically herein improved therapy for various advanced solid tumors with SX by
      elevating the tumor blood flow selectively. This is the first clinical proof that
      modulations of vascular pathophysiology can uniquely accomplish enhanced tumor
      selective delivery of polymeric drugs and thus yielded better clinical outcome.

PMID- 19596664
TI  - Unusual appearance of perirenal fibrosis in renal cell carcinoma simulating a
      tumour.
AB  - Desmoplastic reaction of the stroma is a part and parcel of several malignancies.
      It may be seen within or at a site distant from the main tumour. Irrespective of
      the site of fibrosis in tumours, it portends a poor prognosis as it is generally
      associated with invasion and metastasis. In this report, we present a unique case
      of a 78-year-old male patient with clear cell renal carcinoma (CCRC) who
      presented with a lump in the right loin. On magnetic resonance imaging scan, the
      mass was arising from the middle part of the right kidney. The nephrectomy was
      done and specimen on examination revealed a variegated tumour with another
      whitish solid mass in the surrounding perirenal fat. The kidney tumour showed
      features of CCRC, whereas whitish mass was entirely composed of proliferating
      spindle cells. Therefore, the mass mimicked a second tumour not only on gross but
      even on microscopy. The special stains (Elastic-van Gieson, Masson-Trichrome,
      Periodic acid schiff's, alcian blue and mucicarmine), immunostaining
      (cytokeratin, vimentin, epithelial membrane antigen, smooth muscle actin, S-100,
      HMB-45, CD34 and CD117) patterns and ultrastructural features all, however,
      favoured it to be an extensive peritumoural fibrotic reaction rather than a
      neoplasm. The observation provokes important questions like whether the reaction
      in the index case is an example of tumour-induced fibrosis or is an unassociated
      phenomenon and, in the case of former, what are factors that govern the extent
      and site of fibrosis, i.e. intratumoural, peritumoural or away from the tumour.
      The finding may also help in further research and understanding of the role of
      stroma in cancer progression and developing stromal antigen-targeted therapies in
      CCRC.

PMID- 19596663
TI  - No association between CYP2D6*10 genotype and survival of node-negative Japanese
      breast cancer patients receiving adjuvant tamoxifen treatment.
AB  - OBJECTIVE: The CYP2D6 enzyme plays a major role in converting tamoxifen to its
      active metabolites. We investigated whether there is an association between the
      CYP2D6*10 allele and clinical outcome in node-negative Japanese breast cancer
      patients. METHODS: CYP2D6 genotyping was performed in 154 node-negative breast
      cancer patients who had received adjuvant tamoxifen treatment alone. The CYP2D6
      genotypes were determined using the TaqMan Allelic Discrimination Assay. RESULTS:
      Eighteen percent (28 of 154) of the patients carried the CYP2D6*10/*10 genotype,
      40% the CYP2D6 wild-type (wt)/*10 genotype and 42% the CYP2D6 wt/wt genotype.
      There were no discernible correlations between clinicopathologic parameters and
      the CYP2D6*10 genotype. Next, we determined whether there was a correlation
      between the CYP2D6*10 genotype and survival and found that the clinical outcome
      for patients carrying the CYP2D6*10/*10 genotype was similar to those with other
      genotypes. CONCLUSIONS: Our results suggest that the CYP2D6*10 genotype is
      unlikely to have any clinical significance for prognosis of node-negative
      Japanese breast cancer patients receiving adjuvant tamoxifen alone.

PMID- 19596665
TI  - Factors that affect the duration of the interval between the completion of
      palliative chemotherapy and death.
AB  - BACKGROUND: The purpose of this study was to identify factors that affect the
      duration of the interval between the completion of palliative chemotherapy and
      death. METHODS: We retrospectively analyzed 255 cases in which patients had
      received palliative chemotherapy in the medical oncology division and died during
      the period 2002-2006. Univariate and multivariate analyses were performed to
      identify factors that affected the duration of the interval between the
      completion of chemotherapy and death. RESULTS: There were 133 cases of breast
      cancer, 77 cases of gynecological cancer, 24 cases of primary unknown cancer, and
      21 cases of other cancers. The median interval between the completion of
      chemotherapy and death was 100 days (range, 5-1,206 days). Thirty-two patients
      (12.6%) died within 30 days, and 82 patients (32.3%) died within 60 days. Fifty
      eight (22.7%) patients were symptomatic when chemotherapy was started, and 205
      patients (80.4%) were provided information about palliative care units at the
      start of chemotherapy. The factors associated with a short interval between the
      completion of chemotherapy and death (< or = 90 days) according to the univariate
      analysis were male sex, young age (< or = 45 years), attending physician, poor
      Eastern Cooperative Oncology Group performance status score (3 or 4), obvious
      symptoms, and not having been given information about palliative care units. The
      results of the multivariate analysis indicated that young patients (< or = 45
      years) who had not been referred to a palliative care unit and who had symptoms
      survived for a significantly shorter time interval. CONCLUSION: Young patients
      who were symptomatic tended to choose chemotherapy instead of entering a
      palliative care unit until the very near-the-end-of-life stage.

PMID- 19596666
TI  - Assessing IDU prevalence and health consequences (HCV, overdose and drug-related
      mortality) in a primary care trust: implications for public health action.
AB  - BACKGROUND: We report on an exercise to estimate the prevalence of injecting drug
      use (IDU) and associated harms in a single primary care trust. METHODS: Covariate
      capture-recapture methods to estimate (i) IDU prevalence; respondent driven
      sampling to measure (ii) prevalence of HCV and HIV and record linkage to measure
      (iii) mortality risk. RESULTS: (i) The overall estimated number of IDU was 5540
      (95% confidence interval, CI: 4710-6780) for all cases and 3280 (95% CI: 1940
      4610) for cases matched to primary care register, i.e. a prevalence of 2.2 and
      1.3% aged 15-54, respectively. (ii) The prevalence of HCV, hepatitis B and HIV
      was: 53, 32 and 0.7%. Over 70% of IDU in Bristol reported having at least one
      vaccination for HBV; more than half of those who were HCV positive were
      undiagnosed. (iii) The all-cause and overdose mortality rates for IDU were 0.75
      and 0.4% respectively; and the standardized mortality ratio was 7.8 (95% CI: 5.4
      10.8). CONCLUSION: Locally specific and useful intelligence on injecting and its
      health consequence can be generated to inform local public health action, and may
      contribute information to validate national prevalence estimates.

PMID- 19596667
TI  - Predictors of survival after aortic valve replacement in patients with low-flow
      and high-gradient aortic stenosis.
AB  - AIMS: To identify predictors of survival following aortic valve replacement (AVR)
      in patients with low-flow and high-gradient aortic stenosis (AS). METHODS AND
      RESULTS: Eighty-six patients (aged 71 +/- 10 years) with severe AS [aortic valve
      mean pressure gradient >40 mmHg or valve area <1.0 cm(2)] and left ventricular
      (LV) dysfunction [ejection fraction (EF) <50%] underwent AVR. Cox proportional
      hazards were used to identify independent clinical and echocardiographic
      predictors of mortality. Operative (30-day) mortality was 10%. Peri-operative
      mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak
      systolic pulmonary artery pressure (PSPAP), and serum creatinine (by 12%, 2.3, 28
      mmHg, and 74 mmol/L, respectively, all P < 0.001), NYHA class III-IV (100 vs.
      65%), concomitant CABG (89 vs. 55%), urgent surgery (78 vs. 35%), and longer
      bypass-time (by 28 min, all P < 0.05). Mortality at 4 years was 17%. Univariate
      predictors [hazard ratio (HR)] of 4-year mortality were: lower EF (HR 0.68 per %
      increase, P < 0.001), presence of restrictive LV filling (HR: 3.52, P < 0.001),
      raised PSPAP (HR: 1.07, P < 0.001), and CABG (HR: 4.93, P = 0.037). However, only
      low EF (<40%, HR 0.74, P = 0.030), the presence of restrictive filling (HR 1.77,
      P = 0.033), and raised PSPAP (>45 mmHg, HR 2.71, P = 0.010) remained as
      independent predictors after multivariate analysis. CONCLUSION: The severity of
      pre-operative systolic and diastolic LV dysfunction is the major predictor of
      mortality following AVR for low-flow and high-gradient AS.

PMID- 19596674
TI  - Factors affecting the risk of euthanasia for cows in Danish dairy herds.
AB  - Information about the 7238 Danish dairy cows that died or were euthanized in
      April, May and June of 2008 was obtained from the Danish Cattle Database, and the
      herd-level factors affecting the risk of being euthanized (as opposed to dying
      naturally) were evaluated by logistic regression. In total, 16.6 per cent of the
      dead cows had been euthanized. The odds of euthanasia increased with increasing
      herd size, increasing herd-level milk yield and increasing morbidity in the herd.
      The odds ratio (OR) of euthanasia was 1.13 (P<0.0001) for the effect of an
      increase in herd size of 50 cows, 1.13 (P<0.0001) for an increase in herd-level
      milk yield of 1000 kg energy-corrected milk per cow per year, and 1.31 (P<0.0001)
      for an increase in the average number of diseases recorded per cow per year of
      0.5. The cows' parity and stage of lactation had no effect on their risk of being
      euthanized.

PMID- 19596672
TI  - CB1 and CB2 cannabinoid receptors differentially regulate the production of
      reactive oxygen species by macrophages.
AB  - AIMS: We investigated the mechanism by which cannabinoid receptors-1 (CB1) and -2
      (CB2) modulate inflammatory activities of macrophages. METHODS AND RESULTS: Real
      time polymerase chain reaction showed the predominant CB2 expression in freshly
      isolated human monocytes. PMA, a potent inducer of differentiation, upregulated
      CB1 and increased CB1:CB2 transcript ratio from 1:17.5 to 1:3 in 5 days of
      culture. Immunohistochemistry showed that CB1 protein was colocalized in CD68-
      and CD36-positive macrophages in human atheroma. Through selective expression of
      CB1 or CB2 to thioglycollate-elicited peritoneal macrophages, we proved that CB1
      and CB2 mediate opposing influences on the production of reactive oxygen species
      (ROS). Flow cytometry showed that cannabinoid-induced ROS production by
      macrophages was CB1-dependent. Immunoblotting assays confirmed that macrophage
      CB1, not CB2, induced phosphorylation of p38-mitogen-activated protein kinase,
      which modulated ROS production and the subsequent synthesis of tumour necrosis
      factor-alpha and monocyte chemoattractant protein-1. Pull-down assays showed that
      the Ras family small G protein, Rap1 was activated by CB2. Dominant-negative Rap1
      profoundly enhanced CB1-dependent ROS production by macrophages, suggesting CB2
      Rap1-dependently inhibits CB1-stimulated ROS production. CONCLUSION: CB1 promotes
      pro-inflammatory responses of macrophages through ROS production, which is
      negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with
      selective activation of CB2 may suppress pro-inflammatory responses of
      macrophages.

PMID- 19596675
TI  - In vivo reactions in mice and in vitro reactions in feline cells to implantable
      microchip transponders with different surface materials.
AB  - Tissues of mice that had had microchip transponders with surfaces made of
      bioglass, bioglass with a polypropylene cap, parylene C, titanium or aluminium
      oxide inserted were examined histologically, and the growth of two lines of
      feline fibroblastoid cells around these transponders was examined in vitro. The
      results for bioglass and aluminium oxide were similar. In vitro, there were
      almost no cells around or on the transponders; in vivo, there was often
      granulomatous inflammation in the surrounding tissue. In the case of the
      bioglass, this reaction seemed to be induced by petrolatum, which was added by
      the manufacturer for technical reasons, rather than by the bioglass itself. In
      some of the mice, polypropylene caused a proliferation of granulation tissue. In
      vitro, the cellularity around the transponders was high, but only a moderate
      number of cells were found on the material. In vivo, around the parylene C
      transponders, there were occasionally small fragments of foreign material,
      surrounded by a foreign body reaction; in vitro, the results for parylene C
      resembled those for polypropylene. In vivo, particles of titanium were sometimes
      visible in the connective tissue adjacent to the titanium transponders, and
      sometimes accompanied by a foreign body reaction; in vitro, a confluent layer of
      cells developed on the transponders, with a high cellularity around them.

PMID- 19596676
TI  - Effect of fasting sheep for a short period on the efficacy and safety of
      monepantel.
AB  - Eighteen, six- to seven-month-old lambs were infected experimentally with larvae
      of Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus axei,
      Trichostrongylus colubriformis, Cooperia curticei and Nematodirus spathiger, and
      allocated to three equal groups. The infections were timed to ensure that fourth
      stage larvae were present when groups 1 and 2 were treated orally with
      monepantel. Group 1 was not fed for 24 hours before the treatment, group 2 was
      fed two hours before the treatment and group 3 was fed at the same time as group
      2 but not treated with monepantel. All the sheep had access to water. Worm
      burdens were determined 15 days after the treatments. Fasting or feeding had no
      statistically significant effects on the efficacy of the monepantel solution
      against the nematodes, and the period of fasting had no adverse effects.

PMID- 19596677
TI  - Treatment of Aspergillus species infection in reptiles with itraconazole at
      metabolically scaled doses.

PMID- 19596678
TI  - Extreme monocytosis in a dog with chronic monocytic leukaemia.

PMID- 19596679
TI  - Treatment of dermatophytosis in young cattle with propolis and Whitfield's
      ointment.

PMID- 19596680
TI  - Small animal internship survey.

PMID- 19596681
TI  - Infection control and best practice for small animal veterinary clinics.

PMID- 19596682
TI  - Noise sensitivity in a dog with toxoplasmosis.

PMID- 19596683
TI  - Muscular dystrophy in Cavalier King Charles spaniels.

PMID- 19596684
TI  - Exocrine pancreatic insufficiency treatment study.

PMID- 19596685
TI  - Kinetic and cellular characterization of novel inhibitors of S-nitrosoglutathione
      reductase.
AB  - S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in
      the regulation of S-nitrosothiols (SNOs) in vivo. Knock-out studies in mice have
      shown that GSNOR regulates the smooth muscle tone in airways and the function of
      beta-adrenergic receptors in lungs and heart. GSNOR has emerged as a target for
      the development of therapeutic approaches for treating lung and cardiovascular
      diseases. We report three compounds that exclude GSNOR substrate, S
      nitrosoglutathione (GSNO) from its binding site in GSNOR and cause an
      accumulation of SNOs inside the cells. The new inhibitors selectively inhibit
      GSNOR among the alcohol dehydrogenases. Using the inhibitors, we demonstrate that
      GSNOR limits nitric oxide-mediated suppression of NF-kappaB and activation of
      soluble guanylyl cyclase. Our findings reveal GSNOR inhibitors to be novel tools
      for regulating nitric oxide bioactivity and assessing the role of SNOs in vivo.

PMID- 19596686
TI  - Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome
      inhibition.
AB  - Many cellular processes are regulated by the coordination of several post
      translational modifications that allow a very fine modulation of substrates.
      Recently it has been reported that there is a relationship between sumoylation
      and ubiquitination. Here we propose that the nucleolus is the key organelle in
      which SUMO-1 conjugates accumulate in response to proteasome inhibition. We
      demonstrated that, upon proteasome inhibition, the SUMO-1 nuclear dot
      localization is redirected to nucleolar structures. To better understand this
      process we investigated, by quantitative proteomics, the effect of proteasome
      activity on endogenous nucleolar SUMO-1 targets. 193 potential SUMO-1 substrates
      were identified, and interestingly in several purified SUMO-1 conjugates
      ubiquitin chains were found to be present, confirming the coordination of these
      two modifications. 23 SUMO-1 targets were confirmed by an in vitro sumoylation
      reaction performed on nuclear substrates. They belong to protein families such as
      small nuclear ribonucleoproteins, heterogeneous nuclear ribonucleoproteins,
      ribosomal proteins, histones, RNA-binding proteins, and transcription factor
      regulators. Among these, histone H1, histone H3, and p160 Myb-binding protein 1A
      were further characterized as novel SUMO-1 substrates. The analysis of the nature
      of the SUMO-1 targets identified in this study strongly indicates that
      sumoylation, acting in coordination with the ubiquitin-proteasome system,
      regulates the maintenance of nucleolar integrity.

PMID- 19596690
TI  - Primary percutaneous coronary intervention for acute ST-segment elevation
      myocardial infarction: changing patterns of vascular access, radial versus
      femoral artery.
AB  - OBJECTIVE: To examine the safety and efficacy of emergency transradial primary
      percutaneous coronary intervention for ST-elevation myocardial infarction.
      DESIGN: Single-centre observational study with prospective data collection.
      SETTING: A regional cardiac centre, United Kingdom. PATIENTS: 1051 consecutive
      patients admitted with ST-elevation myocardial infarction, without cardiogenic
      shock, between November 2004 and October 2008. INTERVENTIONS: Percutaneous
      coronary interventions by radial and femoral access MAIN OUTCOME MEASURES: The
      primary outcome measures were procedural success, major vascular complication and
      failed initial access strategy. Secondary outcomes were in-hospital mortality and
      major adverse cardiac and cerebrovascular events, needle-to-balloon times,
      contrast volume used, radiation dose absorbed and time to discharge. Multiple
      regression analysis was used to adjust for potential differences between the
      groups. RESULTS: 571 patients underwent radial access and 480 femoral. A variable
      preference for radial access was observed among the lead operators (between 21%
      and 90%). Procedural success was similar between the radial and femoral groups,
      but major vascular complications were more frequent at the site of femoral access
      (0% radial versus 1.9% femoral, p = 0.001). Failure of the initial access
      strategy was more frequent in the radial group (7.7% versus 0.6%, p<0.001).
      Adjustment for other procedural and clinical predictors did not alter these
      findings. Needle-to-balloon time, as a measure of procedural efficiency, was
      equal for radial and femoral groups. CONCLUSIONS: In the setting of acute ST
      elevation myocardial infarction without cardiogenic shock, transradial primary
      angioplasty is safe, with comparable outcomes to a femoral approach and a lower
      risk of vascular complications.

PMID- 19596691
TI  - Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes
      which confer susceptibility or protection in systemic sclerosis: analyses in 1300
      Caucasian, African-American and Hispanic cases and 1000 controls.
AB  - OBJECTIVE: To determine human leucocyte antigen-class II (HLA-class II) (DRB1,
      DQB1, DQA1 and DPB1) alleles, haplotypes and shared epitopes associated with
      scleroderma (systemic sclerosis (SSc)) and its subphenotypes in a large multi
      ethnic US cohort by a case-control association study. PATIENTS AND METHODS: 1300
      SSc cases (961 white, 178 black and 161 Hispanic subjects) characterised for
      clinical skin forms (limited vs diffuse), SSc-specific autoantibodies
      (anticentromere (ACA), anti-topoisomerase I (ATA), anti-RNA polymerase III (ARA),
      anti-U3 ribonucleoprotein (fibrillarin)) and others were studied using molecular
      genotyping. Statistical analyses in SSc itself by ethnicity, gender, skin type
      and autoantibodies were performed using exact logistic regression modelling for
      dominant, additive and recessive effects from HLA. RESULTS: The strongest
      positive class II associations with SSc in white and Hispanic subjects were the
      DRB1*1104, DQA1*0501, DQB1*0301 haplotype and DQB1 alleles encoding a non-leucine
      residue at position 26 (DQB1 26 epi), while the DRB1*0701, DQA1*0201, DQB1*0202
      haplotype and DRB1*1501 haplotype were negatively correlated and possibly
      protective in dominant and recessive models, respectively. These associations did
      not discriminate between limited and diffuse SSc. SSc in black subjects was
      associated with DRB1*0804, DQA1*0501, DQB1*0301 alleles. DPB1*1301 showed the
      highest odds ratio for ATA (OR = 14). Moreover, it showed no linkage
      disequilibrium or gene interaction with DR/DQ. ACA was best explained by
      DQB1*0501 and DQB1*26 epi alleles and ARA by DRB1*0404, DRB1*11 and DQB1*03
      alleles in white and Hispanic subjects but DRB1*08 in black subjects. CONCLUSION:
      These data indicate unique and multiple HLA-class II effects in SSc, especially
      on autoantibody markers of different subphenotypes.

PMID- 19596692
TI  - Cell-mediated immune responses to influenza vaccination in Wegener's
      granulomatosis.
AB  - BACKGROUND: Both antibody and cell-mediated immune responses are involved in the
      defence against influenza. In Wegener's granulomatosis (WG), antibody responses
      to influenza vaccination appear to be similar to those in healthy controls, but
      cell-mediated responses have not been studied. OBJECTIVE: To determine whether
      cell-mediated responses to influenza vaccination in WG vary from those in
      controls. METHODS: Twenty-five patients with WG and healthy controls received
      subunit influenza vaccine. Peripheral blood mononuclear cells were obtained
      before and 1 month after vaccination. Cell-mediated responses to A/H1N1 and
      A/H3N2 were assessed using interferon gamma (IFN gamma) ELISpot and intracellular
      cytokine staining for IFN gamma, tumour necrosis factor and interleukin 2.
      RESULTS: Before vaccination, patients and controls showed similar recall
      responses to A/H1N1 and A/H3N2. After vaccination, patients and controls showed
      similar levels of increase in spot-forming cells against A/H1N1 and A/H3N2. By
      flow cytometry, upon vaccination, proportions of cytokine-producing CD4 T cells
      increased in patients and controls for A/H1N1 and A/H3N2. CONCLUSIONS: Cell
      mediated responses to influenza vaccination in patients with WG are comparable to
      those in healthy controls.

PMID- 19596693
TI  - Clinical response, pharmacokinetics, development of human anti-chimaeric
      antibodies, and synovial tissue response to rituximab treatment in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To analyse whether persistence of synovial B lineage cells and lack
      of clinical response to rituximab treatment in patients with rheumatoid arthritis
      (RA) are associated with low rituximab serum levels and anti-rituximab antibody
      (ARA) formation. METHODS: Fifty-eight patients with RA were treated with
      rituximab. The clinical response was determined 24 weeks after each treatment
      course using the Disease Activity Score evaluated in 28 joints (DAS28) and EULAR
      response criteria. Rituximab serum levels, ARAs and synovial B lineage cell
      numbers were determined before and after treatment. RESULTS: Four weeks after
      treatment rituximab serum levels were highly variable. Low rituximab levels were
      associated with ARA formation (in five patients (8.6%)) and high baseline
      erythrocyte sedimentation rate. Interestingly, serum rituximab levels were not
      related to persistence of synovial B lineage cells or clinical response.
      Furthermore, response to treatment and re-treatment was similar in ARA-positive
      and ARA-negative patients. CONCLUSION: There is clear variability in serum levels
      after rituximab treatment, but rituximab levels are not lower in patients with
      persistence of synovial B lineage cells or lack of clinical response. The current
      treatment schedule suffices to induce and maintain a clinical response, even when
      ARAs are formed.

PMID- 19596694
TI  - Quantification of cardiovascular biomarkers in patient plasma by targeted mass
      spectrometry and stable isotope dilution.
AB  - Verification of candidate biomarkers requires specific assays to selectively
      detect and quantify target proteins in accessible biofluids. The primary
      objective of verification is to screen potential biomarkers to ensure that only
      the highest quality candidates from the discovery phase are taken forward into
      preclinical validation. Because antibody reagents for a clinical grade
      immunoassay often exist for a small number of candidates, alternative
      methodologies are required to credential new and unproven candidates in a
      statistically viable number of serum or plasma samples. Using multiple reaction
      monitoring coupled with stable isotope dilution MS, we developed quantitative,
      multiplexed assays in plasma for six proteins of clinical relevance to cardiac
      injury. The process described does not require antibodies for immunoaffinity
      enrichment of either proteins or peptides. Limits of detection and quantitation
      for each signature peptide used as surrogates for the target proteins were
      determined by the method of standard addition using synthetic peptides and plasma
      from a healthy donor. Limits of quantitation ranged from 2 to 15 ng/ml for most
      of the target proteins. Quantitative measurements were obtained for one to two
      signature peptides derived from each target protein, including low abundance
      protein markers of cardiac injury in the nanogram/milliliter range such as the
      cardiac troponins. Intra- and interassay coefficients of variation were
      predominantly <10 and 25%, respectively. The configured multiplex assay was then
      used to measure levels of these proteins across three time points in six patients
      undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy.
      These results are the first demonstration of a multiplexed, MS-based assay for
      detection and quantification of changes in concentration of proteins associated
      with cardiac injury in the low nanogram/milliliter range. Our results also
      demonstrate that these assays retain the necessary precision, reproducibility,
      and sensitivity to be applied to novel and uncharacterized candidate biomarkers
      for verification of proteins in blood.

PMID- 19596695
TI  - Development and evaluation of normalization methods for label-free relative
      quantification of endogenous peptides.
AB  - The performances of 10 different normalization methods on data of endogenous
      brain peptides produced with label-free nano-LC-MS were evaluated. Data sets
      originating from three different species (mouse, rat, and Japanese quail), each
      consisting of 35-45 individual LC-MS analyses, were used in the study. Each
      sample set contained both technical and biological replicates, and the LC-MS
      analyses were performed in a randomized block fashion. Peptides in all three data
      sets were found to display LC-MS analysis order-dependent bias. Global
      normalization methods will only to some extent correct this type of bias. Only
      the novel normalization procedure RegrRun (linear regression followed by analysis
      order normalization) corrected for this type of bias. The RegrRun procedure
      performed the best of the normalization methods tested and decreased the median
      S.D. by 43% on average compared with raw data. This method also produced the
      smallest fraction of peptides with interblock differences while producing the
      largest fraction of differentially expressed peaks between treatment groups in
      all three data sets. Linear regression normalization (Regr) performed second best
      and decreased median S.D. by 38% on average compared with raw data. All other
      examined methods reduced median S.D. by 20-30% on average compared with raw data.

PMID- 19596696
TI  - A critical assessment of the role of helical intermediates in amyloid formation
      by natively unfolded proteins and polypeptides.
AB  - Amyloidogenic proteins and polypeptides can be divided into two structural
      classes, namely those which are flexible and are intrinsically disordered in
      their unaggregated state and those which form a compact globular structure with a
      well-defined tertiary fold in their normally soluble state. This review article
      is focused on amyloid formation by natively disordered polypeptides. Important
      examples of this class include islet amyloid polypeptide (IAPP, amylin), pro-IAPP
      processing intermediates, alpha-synuclein, the Abeta peptide, atrial natriuretic
      factor, calcitonin, pro-calcitonin, the medin polypeptide, as well as a range of
      de novo designed peptides. Amyloid formation is a complex process consisting of a
      lag phase during which no detectable fibril material is formed, followed by a
      rapid growth phase that leads to amyloid fibrils. A critical analysis of the
      literature suggests that a subset of intrinsically disordered polypeptides
      populate a helical intermediate during the lag phase. In this scenario, early
      formation of multimeric species is promoted by helix-helix association involving
      one region of the polypeptide chain which leads to a high effective concentration
      of an amyloidogenic sequence located in a different region of the chain. Helical
      intermediates appear to be particularly important in membrane-catalyzed amyloid
      formation and have been implicated in glycosaminoglycan mediated amyloid
      formation as well. There is suggestive evidence that targeting helix-helix
      interactions can be a viable strategy to inhibit amyloid formation. The
      characterization of transient helical intermediates is challenging, but new
      methods are being developed that offer the prospect of providing residue-specific
      information in real time.

PMID- 19596697
TI  - Solution state structures of human pancreatic amylin and pramlintide.
AB  - We have employed pramlintide (prAM) as a surrogate for hAM in CD and NMR studies
      of the conformational preferences of the N-terminal portion of the structure in
      media which do not provide long-lived monomeric solutions of hAM due to its rapid
      conversion to preamyloid beta aggregate states. Direct comparison of hAM and prAM
      could be made under helix-formation-favoring conditions. On the basis of CD and
      NMR studies: (i) the Cys(2)-Cys(7) loop conformation has a short-span of helix
      (Ala(5)-Cys(7)); (ii) the extent to which this helix propagates further into the
      sequence is medium-dependent; a helix from Ala(5) through Ser(20) (with end
      fraying from His(18) onward) is observed in aqueous fluoroalcohol media; (iii) in
      12+ vol.% HFIP, the amyloidogenic region of hAM forms a second helical domain
      (Phe(23)-Ser(29)); (iv) the two helical regions of hAM do not have any specific
      geometric relationship as they are connected by a flexible loop that takes
      different conformations and (v) although the extreme C-terminus is essential for
      bioactivity, it is found to be extensively randomized with conformer
      interconversions occurring at a much faster rate than that is observed in the
      remainder of the peptide sequence. Two NMR-derived structures of the 1-22
      sequence fragment of hAM have been derived. The work also serves to illustrate
      improved methods for the NMR characterization of helices. A detailed quantitative
      analysis of the NOE intensities observed in aqueous HFIP revealed alternative
      conformations in the C-terminal portion of the common amylin helix, a region that
      is known to be involved in the biorecognition phenomena leading to
      amyloidogenesis. Even though the SNN sequence appears to be a flexible loop, the
      chemical shifts (and changes induced upon helix structuring) suggest some
      interactions between the loop and the amyloidogenic segment of hAM that occur on
      partial helix formation.

PMID- 19596698
TI  - Are plant growth and photosynthesis limited by pre-drought following rewatering
      in grass?
AB  - Although the relationship between grassland productivity and soil water status
      has been extensively researched, the responses of plant growth and photosynthetic
      physiological processes to long-term drought and rewatering are not fully
      understood. Here, the perennial grass (Leymus chinensis), predominantly
      distributed in the Euro-Asia steppe, was used as an experimental plant for an
      irrigation manipulation experiment involving five soil moisture levels [75-80, 60
      75, 50-60, 35-50, and 25-35% of soil relative water content (SRWC), i.e. the
      ratio between present soil moisture and field capacity] to examine the effects of
      soil drought and rewatering on plant biomass, relative growth rate (RGR), and
      photosynthetic potential. The recovery of plant biomass following rewatering was
      lower for the plants that had experienced previous drought compared with the
      controls; the extent of recovery was proportional to the intensity of soil
      drought. However, the plant RGR, leaf photosynthesis, and light use potential
      were markedly stimulated by the previous drought, depending on drought intensity,
      whereas stomatal conductance (g(s)) achieved only partial recovery. The results
      indicated that g(s) may be responsible for regulating actual photosynthetic
      efficiency. It is assumed that the new plant growth and photosynthetic potential
      enhanced by pre-drought following rewatering may try to overcompensate the great
      loss of the plant's net primary production due to the pre-drought effect. The
      present results highlight the episodic effects of drought on grass growth and
      photosynthesis. This study will assist in understanding how degraded ecosystems
      can potentially cope with climate change.

PMID- 19596700
TI  - Molecular mechanism for jasmonate-induction of anthocyanin accumulation in
      Arabidopsis.
AB  - Anthocyanins are important plant pigments that fulfil many physiological and
      ecological functions. Anthocyanin biosynthesis is controlled by numerous
      regulatory factors at the transcriptional level. Jasmonates (JAs) has been shown
      to induce anthocyanin accumulation in several plant species, however, the
      molecular mechanism for JA-regulated anthocyanin accumulation remains unknown. In
      this study, genetic, molecular, and physiological approaches were used to reveal
      the molecular basis of JA-regulated pigmentation in Arabidopsis. It was found
      that the F-box protein COI1 was required for JA-specific induced expression of
      the 'late' anthocyanin biosynthetic genes DFR, LDOX, and UF3GT. It is further
      demonstrated that COI1 was essential for JA-induction of transcription factors
      PAP1, PAP2, and GL3. It is speculated that COI1 regulates the expression of the
      transcription factors, including PAP1, PAP2, and GL3, which mediates the 'late'
      anthocyanin biosynthetic genes DFR, LDOX, and UF3GT, thereby modulating JA
      induced anthocyanin biosynthesis in Arabidopsis.

PMID- 19596699
TI  - Identification and localization of the bilitranslocase homologue in white grape
      berries (Vitis vinifera L.) during ripening.
AB  - A homologue of the mammalian bilirubin transporter bilitranslocase (BTL) (TCDB
      2.A.65.1.1), able to perform an apparent secondary active transport of
      flavonoids, has previously been found in carnation petals and red grape berries.
      In the present work, a BTL homologue was also shown in white berries from Vitis
      vinifera L. cv. Tocai/Friulano, using anti-sequence antibodies specific for rat
      liver BTL. This transporter, similarly to what found in red grape, was localized
      in the first layers of the epidermal tissue and in the vascular bundle cells of
      the mesocarp. In addition, a strong immunochemical reaction was detected in the
      placental tissue and particularly in peripheral integuments of the seed. The
      protein was expressed during the last maturation stages in both skin and pulp
      tissues and exhibited an apparent molecular mass of c. 31 kDa. Furthermore, the
      transport activity of such a carrier, measured as bromosulphophthalein (BSP)
      uptake, was detected in berry pulp microsomes, where it was inhibited by specific
      anti-BTL antibodies. The BTL homologue activity exhibited higher values, for both
      K(m) and V(max), than those found in the red cultivar. Moreover, two non
      pigmented flavonoids, such as quercetin (a flavonol) and eriodictyol (a
      flavanone), inhibited the uptake of BSP in an uncompetitive manner. Such results
      strengthen the hypothesis that this BTL homologue acts as a carrier involved also
      in the membrane transport of colourless flavonoids and demonstrate the presence
      of such a carrier in different organs and tissues.

PMID- 19596701
TI  - Does reduced-intensity allogeneic transplantation confer a survival advantage to
      patients with poor prognosis chronic lymphocytic leukaemia? A case-control
      retrospective analysis.
AB  - BACKGROUND: Reduced-intensity conditioning (RIC) allogeneic haemopoietic cell
      transplantation (allo-HCT) is increasingly considered as a therapeutic option for
      younger patients with poor-risk chronic lymphocytic leukaemia (CLL). In this
      retrospective analysis, we assessed the outcomes of CLL patients undergoing RIC
      allo-HCT compared with a group of matched controls that were candidates for
      transplantation but did not have a suitable donor or refused the procedure.
      PATIENTS AND METHODS: Cases comprised 37 patients who underwent RIC allo-HCT.
      Haemopoietic cell grafts were harvested from HLA-matched siblings (27) and
      unrelated donors (7). Controls consisted of 43 patients from the same
      institutions who received conventional therapy only. Matching variables were age
      at diagnosis and time to first CLL-specific therapy. RESULTS: Both patient groups
      were well balanced in terms of cytogenetics by FISH, CD38 and ZAP-70 expression,
      and immunoglobulin heavy-chain variable region mutational status. Median overall
      survival was 113 months for HCT patients and 85 months for controls when
      calculated from time of diagnosis (P = 0.072) and 103 and 67 months,
      respectively, when calculated from time of first therapy (P = 0.041). CONCLUSION:
      RIC allo-HCT is a reasonable option for patients with high-risk CLL. However,
      these results require confirmation before the procedure can be recommended
      outside clinical trials.

PMID- 19596703
TI  - The acute chest syndrome of sickle cell disease following aortic valve
      replacement.
AB  - The acute chest syndrome (ACS) of sickle cell disease (SCD) is a leading cause of
      death in SCD, with a high incidence following surgery, though only one case has
      been reported following cardiac surgery. We present a case of ACS in an adult
      undergoing aortic valve replacement (AVR) despite instituting established peri
      operative optimization measures to prevent sickling. Early diagnosis of this
      condition in our patient as a distinct clinical entity facilitated appropriate,
      specific therapy and a good subsequent postoperative recovery. Greater
      recognition of this syndrome in the growing number of adult sickle cell patients
      presenting for cardiac surgery may help improve their outcome.

PMID- 19596702
TI  - Prognostic impact of discordance between triple-receptor measurements in primary
      and recurrent breast cancer.
AB  - BACKGROUND: We evaluated discordance in expression measurements for estrogen
      receptor (ER), progesterone receptor (PR), and HER2 between primary and recurrent
      tumors in patients with recurrent breast cancer and its effect on prognosis.
      METHODS: A total of 789 patients with recurrent breast cancer were studied. ER,
      PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH.
      Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%,
      respectively. Primary and recurrent tumors were classified as triple receptor
      negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e.
      expressing at least one receptor). Discordance was correlated with
      clinical/pathological parameters. RESULTS: Discordance for ER, PR, and HER2 was
      18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had
      significantly better post-recurrence survival (PRS) than discordant cases;
      patients with discordant receptor status had similarly unfavorable survival as
      patients with concordant TNBC. IHC scores for ER and PR showed weak concordance
      between primary and recurrent tumors. Concordance of HER2-FISH scores was higher.
      CONCLUSIONS: Concordance of quantitative hormone receptor measurements between
      primary and recurrent tumors is modest consistent with suboptimal reproducibility
      of measurement methods, particularly for IHC. Discordant cases have poor survival
      probably due to inappropriate use of targeted therapies. However, biological
      change in clinical phenotype cannot be completely excluded.

PMID- 19596704
TI  - Asymptomatic false aneurysm of the right coronary sinus treated by a
      reimplantation valve sparing technique.
AB  - We describe the case of a 65-year-old man who presented with a false aneurysm of
      the right aortic coronary sinus, discovered after a routine medical examination.
      A complete resection of the aortic root and a reimplantation technique were
      performed. Herein, we describe the technical approach and immediate follow-up.

PMID- 19596705
TI  - EuroSCORE predicts postoperative mortality, certain morbidities, and recovery
      time.
AB  - EuroSCORE (European System for Cardiac Operative Risk Evaluation) used for
      calculating the risk of the postoperative mortality rate for patients undergoing
      open-heart surgery may be able to predict postoperative complications as well.
      Consecutive cases of isolated on-pump coronary artery bypass grafting (CABG)
      (n=1552) performed between 1991 and 2006 at our hospital group were placed into a
      systematic database. Patients were stratified using additive EuroSCORE. Incidence
      of postoperative mortality, morbidity (bleeding, heart failure, mediastinitis,
      pneumonia, myocardial infarction, renal failure, and stroke), and recovery time
      (intubation time, ICU stay, and postoperative length of stay) was assessed in
      each EuroSCORE group. EuroSCORE was well correlated with mortality, total
      incidence of major complications, heart failure, renal failure, stroke, pneumonia
      and mediastinitis, and three parameters of recovery time. Postoperative
      myocardial infarction and incidence of bleeding were not correlated with
      EuroSCORE. EuroSCORE can predict not only mortality but also postoperative
      complications and recovery time.

PMID- 19596706
TI  - Resection of intrapericardial hibernoma associated with constrictive
      pericarditis.
AB  - Hibernoma is a benign soft-tissue tumor, which arises from the remnants of fetal
      brown adipose tissue. Out of less than 300 cases of hibernoma described to date,
      pericardial sac is an unusual localization to develop. When the tumor increases
      in size, this benign pathology can lead to compression of cardiac chambers and
      cause life-threatening complications in an asymptomatic patient. Here, the
      authors present the case of a 20-year-old male who underwent an operation for the
      treatment of constrictive pericarditis, in which an intrapericardial sessile
      lesion over diaphragmatic surface of pericardial sac was incidentally discovered.
      The tumor was excised and diagnosed as hibernoma. No recurrence was evident two
      years after the procedure.

PMID- 19596707
TI  - Early acute aortic dissection of the donor aorta after orthotopic heart
      transplantation.
AB  - Acute type A aortic dissection is an uncommon complication after orthotopic heart
      transplantation and usually affects the native aorta. Seven cases reported in the
      literature describe an aortic dissection confined to the donor aorta and only in
      two of them were they detected during the early postoperative period. We describe
      the case of a 58-year-old man, the recipient of a cardiac allograft for ischemic
      cardiomyopathy 20 days earlier, who presented an acute type A aortic dissection
      limited to the donor aorta. Transesophageal echocardiography revealed severe
      aortic regurgitation and an intimal tear 2 cm above commissures. The patient was
      successfully treated with a composite valve graft. This case is the first
      successful repair in a cardiac allograft with acute aortic dissection of the
      donor aorta during the early postoperative period using a Bentall procedure.

PMID- 19596708
TI  - Omics and bioinformatics: an essential toolbox for systems analyses of plant
      functions beyond 2010.

PMID- 19596709
TI  - Toward understanding of carbohydrate binding and substrate specificity of a
      glycosyl hydrolase 18 family (GH-18) chitinase from Trichoderma harzianum.
AB  - Surface plasmon resonance (SPR) has been used to assay the roles of amino acid
      residues in the substrate binding cleft of Trichoderma harzianum chitinase
      Chit42, which belongs to the glycoside hydrolase family 18 (GH-18). Nine
      different Chit42 variants having amino acid mutations along the binding site
      cleft at subsites -4 to +2 were created and characterized with regard to their
      affinity toward chitinous and non-chitinous oligosaccharides. The catalytically
      inactive Chit42 mutant E172Q was used as the template for making the additional
      mutations. The E172Q mutant bound chitinoligosaccharides (tetra-, penta- and
      hexamer) with an increasing affinity from 12 to 0.2 microM whereas no binding of
      chitinbiose, -triose or 3'-sialyl-N-acetyllactosamine (Neu5Acalpha-3Galbeta
      4GlcNAc) could be measured, indicative of significantly lower affinity for these
      shorter oligosaccharides. The strongest binding affinity was displayed toward
      allosamidin, a transition state analog (K(d) = 3 nM), and this was shown to be
      dependent on the E172 residue, the acid/base catalyst of Chit42. Hydrogen bonding
      by the glutamic acid E317 between subsites -2 and -3 and particularly the
      stacking interactions by tryptophanes at subsites -3 and +2 provided to be
      important, as mutations to these amino acids had a substantial negative effect to
      the overall binding affinity. Moreover, the substrate binding specificity of
      Chit42 could be altered toward binding of GlcNbeta-4(GlcNAc)(4) by providing a
      counter charge through substitution of residue T133 at subsite -3 against
      aspartic acid. In addition, the introduction of glutamine and particularly an
      asparagine residue at position 133 seemed to broaden the substrate preference of
      Chit42 toward Galbeta-4(GlcNAc)(4).

PMID- 19596710
TI  - Vitamin C deficiency in a population of young Canadian adults.
AB  - A cross-sectional study of the 979 nonsmoking women and men aged 20-29 years who
      participated in the Toronto Nutrigenomics and Health Study from 2004 to 2008 was
      conducted to determine the prevalence of serum ascorbic acid (vitamin C)
      deficiency and its association with markers of chronic disease in a population of
      young Canadian adults. High performance liquid chromatography was used to
      determine serum ascorbic acid concentrations from overnight fasting blood
      samples. A 1-month, 196-item food frequency questionnaire was used to assess
      dietary intakes. Results showed that 53% of subjects had adequate, 33% had
      suboptimal, and 14% had deficient levels of serum ascorbic acid. Subjects with
      deficiency had significantly higher measurements of mean C-reactive protein,
      waist circumference, body mass index, and blood pressure than did subjects with
      adequate levels of serum ascorbic acid. The odds ratio for serum ascorbic acid
      deficiency was 3.43 (95% confidence interval: 2.14, 5.50) for subjects who
      reported not meeting the recommended daily intake of vitamin C compared with
      those who did. Results suggest that 1 of 7 young adults has serum ascorbic acid
      deficiency, in part, because of unmet recommended dietary intakes. Furthermore,
      serum ascorbic acid deficiency is associated with elevated markers of chronic
      disease in this population of young adults, which may have long-term adverse
      health consequences.

PMID- 19596711
TI  - Use of supplements of multivitamins, vitamin C, and vitamin E in relation to
      mortality.
AB  - In this cohort study, the authors evaluated how supplemental use of
      multivitamins, vitamin C, and vitamin E over a 10-year period was related to 5
      year total mortality, cancer mortality, and cardiovascular disease (CVD)
      mortality. Participants (n = 77,719) were Washington State residents aged 50-76
      years who completed a mailed self-administered questionnaire in 2000-2002.
      Adjusted hazard ratios and 95% confidence intervals were computed using Cox
      regression. Multivitamin use was not related to total mortality. However, vitamin
      C and vitamin E use were associated with small decreases in risk. In cause
      specific analyses, use of multivitamins and use of vitamin E were associated with
      decreased risks of CVD mortality. The hazard ratio comparing persons who had a 10
      year average frequency of multivitamin use of 6-7 days per week with nonusers was
      0.84 (95% confidence interval: 0.70, 0.99); and the hazard ratio comparing
      persons who had a 10-year average daily dose of vitamin E greater than 215 mg
      with nonusers was 0.72 (95% confidence interval: 0.59, 0.88). In contrast,
      vitamin C use was not associated with CVD mortality. Multivitamin and vitamin E
      use were not associated with cancer mortality. Some of the associations we
      observed were small and may have been due to unmeasured healthy behaviors that
      were more common in supplement users.

PMID- 19596715
TI  - Australian studies of A/H1N1 flu could help northern hemisphere this winter.

PMID- 19596713
TI  - Distinguishing among evolutionary models for the maintenance of gene duplicates.
AB  - Determining the evolutionary forces responsible for the maintenance of gene
      duplicates is key to understanding the processes leading to evolutionary
      adaptation and novelty. In his highly prescient book, Susumu Ohno recognized that
      duplicate genes are fixed and maintained within a population with 3 distinct
      outcomes: neofunctionalization, subfunctionalization, and conservation of
      function. Subsequent researchers have proposed a multitude of population genetic
      models that lead to these outcomes, each differing largely in the role played by
      adaptive natural selection. In this paper, I present a nonmathematical review of
      these models, their predictions, and the evidence collected in support of each of
      them. Though the various outcomes of gene duplication are often strictly
      associated with the presence or absence of adaptive natural selection, I argue
      that determining the outcome of duplication is orthogonal to determining whether
      natural selection has acted. Despite an ever-growing field of research into the
      fate of gene duplicates, there is not yet clear evidence for the preponderance of
      one outcome over the others, much less evidence for the importance of adaptive or
      nonadaptive forces in maintaining these duplicates.

PMID- 19596712
TI  - Duration of coherence intervals in electrical brain activity in perceptual
      organization.
AB  - We investigated the relationship between visual experience and temporal intervals
      of synchronized brain activity. Using high-density scalp electroencephalography,
      we examined how synchronized activity depends on visual stimulus information and
      on individual observer sensitivity. In a perceptual grouping task, we varied the
      ambiguity of visual stimuli and estimated observer sensitivity to this variation.
      We found that durations of synchronized activity in the beta frequency band were
      associated with both stimulus ambiguity and sensitivity: the lower the stimulus
      ambiguity and the higher individual observer sensitivity the longer were the
      episodes of synchronized activity. Durations of synchronized activity intervals
      followed an extreme value distribution, indicating that they were limited by the
      slowest mechanism among the multiple neural mechanisms engaged in the perceptual
      task. Because the degree of stimulus ambiguity is (inversely) related to the
      amount of stimulus information, the durations of synchronous episodes reflect the
      amount of stimulus information processed in the task. We therefore interpreted
      our results as evidence that the alternating episodes of desynchronized and
      synchronized electrical brain activity reflect, respectively, the processing of
      information within local regions and the transfer of information across regions.

PMID- 19596716
TI  - Medecins Sans Frontieres campaigns to increase treatment of Chagas disease.

PMID- 19596718
TI  - Potential causes and health effects of rising global food prices.

PMID- 19596719
TI  - Eating healthily and rising food prices.

PMID- 19596720
TI  - Thyroid swellings.

PMID- 19596722
TI  - Legal loophole sees hundreds of Dutch cafes escape smoking ban.

PMID- 19596723
TI  - Cases of A/H1N1 flu are nearing epidemic levels in London and West Midlands, say
      GPs.

PMID- 19596725
TI  - Barely started and already left behind: a descriptive analysis of the mathematics
      ability demonstrated by young deaf children.
AB  - This study examined young deaf children's early informal/formal mathematical
      knowledge as measured by the Test of Early Mathematics Ability (TEMA-3). Findings
      from this study suggest that prior to the onset of formal schooling, young deaf
      children might already demonstrate evidence of academic delays. Of these 28
      participants (4-6 years of age), for whom data were analyzed, none received a
      score on the TEMA-3, indicating above-"average" ability according to normative
      ranking. More than half of participants received scores substantially below
      average with 11 participants receiving scores a year or more behind normative age
      equivalent scores. Upon more focused analysis, specific areas of difficulty were
      found to include word/story problems, skip counting (i.e., counting by twos,
      threes, etc.), number comparisons, the reading/writing of two to three digit
      numbers, and addition/subtraction number facts. A qualitative analysis of the
      answers participants gave and the behaviors they demonstrated while answering the
      test items was conducted and revealed possible explanations for why specific test
      items may have been challenging. Implications of findings for parents, early
      interventionists, and teachers of young deaf children are discussed.

PMID- 19596726
TI  - Association of metabolic syndrome with smoking and alcohol intake in Japanese
      men.
AB  - INTRODUCTION: There have been conflicting findings on whether metabolic syndrome
      (MetS) is associated with smoking and alcohol intake. This study investigated the
      association of MetS with smoking and alcohol intake. METHODS: MetS was defined
      according to the International Diabetes Federation criteria, and smoking and
      alcohol intake were evaluated for 1,215 Japanese male workers using a
      questionnaire. The association of MetS with smoking and alcohol intake was
      assessed using logistic regression after adjusting for potential confounders.
      Proportional analyses for the prevalence of MetS among smoking and alcohol intake
      were performed as well. RESULTS: Among the subjects, 148 (12%) were diagnosed
      with MetS, 485 (40%) were smokers, and 954 (79%) were regular alcohol users. The
      prevalence of MetS was the highest (19%) in smokers who did not drink, followed
      by smokers who also drank (13%), nonsmokers who drank (12%), and those who
      neither smoked nor drank (7%). Smoking itself was positively related to MetS
      (odds ratio [OR] = 1.4; 95% CI = 1.1-2.1) and MetS components, including larger
      waist circumference (OR = 1.5; 95% CI = 1.2-1.9), elevated triglyceride (OR =
      1.9; 95% CI = 1.4-2.4), and reduced high-density lipoprotein cholesterol (OR =
      1.7; 95% CI = 1.1-2.7). Alcohol intake was not significantly related to MetS; it
      was positively correlated only to higher fasting plasma glucose (OR = 1.7; 95% CI
      = 1.1-2.6). DISCUSSION: These results suggest that cigarette smoking is an
      independent risk factor for MetS, but the risk does not seem to be exaggerated by
      alcohol intake.

PMID- 19596727
TI  - Psychometric qualities of the Brazilian versions of the Fagerstrom Test for
      Nicotine Dependence and the Heaviness of Smoking Index.
AB  - INTRODUCTION: This study examined the psychometric properties of the Brazilian
      versions of the Fagerstrom Test for Nicotine Dependence (FTND) and the Heaviness
      of Smoking Index (HSI). METHODS: The test-retest reliability of the FTND was
      assessed in a sample of 61 smoking university students, with a 15-day interval
      between assessments. The interrater reliability was examined in 30 smoking
      patients of a psychosocial care center for alcohol and drug users (PCC-AD). The
      reliability coefficient was estimated by the kappa and intraclass correlation
      coefficients. The predictive validity, internal consistency, and factor structure
      of the FTND and the HSI were evaluated by factor analysis in 271 smokers treated
      at an emergency unit and at the PCC-AD. The gold standard was the nicotine
      dependence criteria of DSM-IV, as assessed by the Structured Clinical Interview
      for DSM-IV. RESULTS: The FTND showed high reliability, with correlation
      coefficients of .92 for test-retest reliability and .99 for interrater
      reliability. Both the FTND and the HSI presented high levels of sensitivity and
      specificity. The internal consistency evaluation yielded a Cronbach's alpha
      coefficient of .83 for the FTND and of .56 for the HSI. An exploratory factor
      analysis found 2 factors in the FTND, which were validated by a confirmatory
      factor analysis. DISCUSSION: The results obtained in this study confirm the
      validity and reliability of the Brazilian versions of the FTND and the HSI.

PMID- 19596728
TI  - Can exergaming contribute to improving physical activity levels and health
      outcomes in children?
AB  - Physical inactivity among children is a serious public health problem. It has
      been suggested that high levels of screen time are contributory factors that
      encourage sedentary lifestyles in young people. As physical inactivity and
      obesity levels continue to rise in young people, it has been proposed that new
      generation active computer- and video-console games (otherwise known as
      "exergaming") may offer the opportunity to contribute to young people's energy
      expenditure during their free time. Although studies have produced some
      encouraging results regarding the energy costs involved in playing active video
      console games, the energy costs of playing the authentic versions of activity
      based video games are substantially larger, highlighting that active gaming is no
      substitute for real sports and activities. A small number of exergaming
      activities engage children in moderate-intensity activity, but most do not. Only
      3 very small trials have considered the effects of exergaming on physical
      activity levels and/or other health outcomes in children. Evidence from these
      trials has been mixed; positive trends for improvements in some health outcomes
      in the intervention groups were noted in 2 trials. No adequately powered
      randomized, controlled trial has been published to date, and no trial has
      assessed the long-term impact of exergaming on children's health. We now need
      high-quality randomized, controlled trials to evaluate the effectiveness and
      sustainability of exergaming, as well as its clinical relevance; until such
      studies take place, we should remain cautious about its ability to positively
      affect children's health.

PMID- 19596730
TI  - Early pubertal development in Chinese girls.

PMID- 19596729
TI  - Reducing immunization discomfort in 4- to 6-year-old children: a randomized
      clinical trial.
AB  - OBJECTIVE: The goal was to test a multifaceted distraction method designed to
      reduce injection-associated pain in school-aged children. METHODS: A clinical
      trial evaluated 41 children, 4 to 6 years of age, who were given 3 standard
      prekindergarten immunizations; 21 were assigned randomly to an office routine
      control group, whereas 20 received a multifaceted, discomfort-reducing
      intervention. The intervention added verbal suggestions of diminished sensation
      and a visual focusing activity to the use of ethyl chloride, an established pain
      reducing measure. The distraction materials used for the intervention consisted
      of topical ethyl chloride spray, an improvised, plastic, multipronged arm
      gripper, and a vibrating instrument descending on the contralateral arm, which
      provided the focusing task and visual distraction. RESULTS: According to patient
      and parent Faces Pain Scale-Revised scores and nonblinded, video-taped
      observations scored according to the face-legs-activity-crying-consolability
      method, the intervention group showed highly significant reductions in pain and
      discomfort, compared with the control group (patient self-report, P < .0013;
      parent report, P < .0002; observation score, P < .0001). CONCLUSION: This
      multifaceted distraction intervention reduced significantly the pain and
      discomfort of childhood immunizations in children 4 to 6 years of age.

PMID- 19596732
TI  - Terrorism-related perceived stress, adolescent depression, and social support
      from friends.
AB  - BACKGROUND: Terrorism leads to adolescent depression, but little is known about
      protective factors. We investigated 90 adolescents (in grades 7-9) residing in
      Dimona, Israel, before and after their exposure to a suicide bombing. OBJECTIVE:
      To examine the prospective effect of social support from friends, parents, and
      school personnel on the link between bombing-related perceived stress and
      adolescent depression. METHODS: Seven months prior to the suicide bombing,
      adolescents completed questionnaires as part of an ongoing investigation of youth
      risk/resilience under stress. The focus of the present study was on the Perceived
      Social Support Scale. One month subsequent to the suicide bombing, participants
      were interviewed by telephone about their bombing-related perceived stress (a 1
      item measure) and depression (the Center for Epidemiologic Studies Child
      Depression Scale). RESULTS: Bombing-related perceived stress was associated with
      an increase in continuous levels of depression from before to after the bombing
      (beta = .29; P = .006). Prebombing social support from friends buffered against
      this effect (beta = -.29; P = .010). Adolescents reporting high bombing-related
      perceived stress evinced an increase in depression if they reported low levels of
      friends' support (beta = .61; P < .001) but not high levels of friends' support
      (beta = .00; P = .98). In addition, social support from friends predicted an
      increase in adolescent depression over time when bombing-related perceived stress
      was low (beta = .34; P = .026). CONCLUSION: In adolescence, social support from
      friends might protect against the depressogenic effect of terrorism-related
      perceived stress.

PMID- 19596731
TI  - Empiric use of potassium citrate reduces kidney-stone incidence with the
      ketogenic diet.
AB  - OBJECTIVE: Kidney stones are an adverse event with the ketogenic diet (KD),
      occurring in approximately 6% of children who are started on this therapy for
      intractable epilepsy. Potassium citrate (Polycitra K) is a daily oral supplement
      that alkalinizes the urine and solubilizes urine calcium, theoretically reducing
      the risk for kidney stones. METHODS: Children who started the KD from 2000 to
      2008 at Johns Hopkins Hospital, with at least 1 month of follow-up, were
      evaluated (N = 313). From 2000 to 2005, children were treated with daily
      Polycitra K at 2 mEq/kg per day only in the setting of identified hypercalciuria,
      whereas, since 2006, it has been started for all children empirically at KD
      onset. RESULTS: Polycitra K was administered to 198 children preventatively
      overall, 4 (2.0%) of whom developed kidney stones, compared with 11 (10.5%) of
      105 who did not receive Polycitra K (P = .003). Two children since 2006 refused
      Polycitra K, 1 of whom developed a kidney stone. Successful empiric
      administration of Polycitra K at KD onset resulted in a kidney-stone incidence of
      0.9% (1 of 106) compared with administration only because of hypercalciuria, 6.7%
      (13 of 195; P = .02). Polycitra K resulted in less acidic urine (mean pH: 6.8 vs
      6.2; P = .002) but not reduced serum acidosis. No adverse effects of oral
      citrates were reported. CONCLUSIONS: Oral potassium citrate is an effective
      preventive supplement against kidney stones in children who receive the KD,
      achieving its goal of urine alkalinization. Universal supplementation is
      warranted.

PMID- 19596733
TI  - Transporting children with special health care needs: comparing recommendations
      and practice.
AB  - OBJECTIVE: We compare the use of the American Academy of Pediatrics (AAP)
      guidelines for the safe transportation of children with special health care needs
      (CSHCN) with reported and observed practices. METHODS: This observational study
      was based on a convenience sample of vehicles exiting the garage of a tertiary
      children's hospital. Certified child passenger safety technicians with a health
      care background and specialized training in the transportation of CSHCN gathered
      the driver's demographic information and the child's reported medical condition,
      weight, age, clinic visited, and relation to the driver. The safety technicians
      observed the car safety seat (CSS) type, vehicle seating position, and if the
      child required postural support. RESULTS: During the study, 275 drivers
      transporting 294 CSHCN were observed. Overall, most drivers complied with AAP
      recommendations by using a standard CSS seat (75.4%). Among the seats evaluated,
      241 (82.0%) were the appropriate choice, but only 75 (26.8%) of 280 assessed had
      no misuses. Approximately 24% of the drivers modified the CSS, and 19.4% of the
      children would have benefited from additional body-positioning support. Only 8%
      of medical equipment was properly secured. CONCLUSIONS: Although most drivers
      seemed to choose the appropriate seat, many had at least 1 misuse. Drivers
      complied with most AAP recommendations; however, some deviated to facilitate care
      of the child during transport. Discussions with parents or caregivers about the
      proper transportation of CSHCN and referrals to child passenger safety
      technicians with special training may improve safety, care, and comfort in the
      vehicle.

PMID- 19596735
TI  - Injuries associated with bathtubs and showers among children in the United
      States.
AB  - OBJECTIVE: The goal was to describe the epidemiological features of injuries
      associated with bathtubs and showers, especially those related to slips, trips,
      and falls, among US children. METHODS: A retrospective study was performed by
      using nationally representative data from the US Consumer Product Safety
      Commission National Electronic Injury Surveillance System from 1990 through 2007
      for children <or=18 years of age. RESULTS: There were an estimated 791 200
      bathtub- and shower-related injuries among children <or=18 years of age who were
      treated in US emergency departments in 1990-2007, with an average of 43 600 cases
      per year or approximately 5.9 injuries per 10 000 US children per year. The
      largest number of injuries involved children 2 years of age; children <or=4 years
      accounted for 54.3% of injuries. The most common diagnosis was laceration
      (59.5%). The most common mechanism of injury was a slip, trip, or fall,
      accounting for 81.0% of cases or 4.6 injuries per 10 000 US children per year.
      The most frequently injured body part was the face (48.0%), followed by the
      head/neck (15.0%). The majority (71.3%) of injuries occurred in a bathtub. Of the
      cases with a known place of injury, 97.1% occurred at home. An estimated 2.8% of
      patients were admitted, transferred to another hospital, or held for observation.
      CONCLUSIONS: This is the first study on bathtub- and shower-related injuries
      using nationally representative data. Slips, trips, and falls in bathtubs and
      showers are a common cause of injury among children, especially children <or=4
      years of age. The incidence of these injuries may be decreased by increasing the
      coefficient of friction of bathtub and shower surfaces.

PMID- 19596734
TI  - Mental health treatment patterns in perinatally HIV-infected youth and controls.
AB  - BACKGROUND: Youths perinatally infected with HIV often receive psychotropic
      medication and behavioral treatment for emotional and behavioral symptoms. We
      describe patterns of intervention for HIV-positive youth and youth in a control
      group in the United States. METHODS: Three hundred nineteen HIV-positive youth
      and 256 controls, aged 6 to 17 years, enrolled in the International Maternal
      Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study
      of psychiatric symptoms. One hundred seventy-four youth in the control group were
      perinatally exposed to HIV, and 82 youth were uninfected children living in
      households with HIV-positive members. Youth and their primary caregivers
      completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      referenced symptom-rating scales. Children's medication and behavioral
      psychiatric intervention histories were collected at entry. We evaluated the
      association of past or current psychiatric treatment with HIV status, baseline
      symptoms, and impairment by using multiple logistic regression, controlling for
      potential confounders. RESULTS: HIV-positive youth and youth in the control group
      had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to
      15%). One hundred four (18%) participants received psychotropic medications
      (stimulants [14%], antidepressants [6%], and neuroleptic agents [4%]), and 127
      (22%) received behavioral treatment. More HIV-positive youth than youth in the
      control group received psychotropic medication (23% vs 12%) and behavioral
      treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV
      positive children had twice the odds of children in the control group of having
      received stimulants and >4 times the odds of having received antidepressants.
      Caregiver-reported symptoms or impairment were associated with higher odds of
      intervention than reports by children alone. CONCLUSIONS: HIV-positive children
      are more likely to receive mental health interventions than control-group
      children. Pediatricians and caregivers should consider available mental health
      treatment options for all children living in families affected by HIV.

PMID- 19596737
TI  - Playing active video games increases energy expenditure in children.
AB  - OBJECTIVE: To compare energy expenditure rates in children playing the physically
      active video games, Dance Dance Revolution (DDR) and Nintendo's Wii Sports in
      relation to treadmill walking. METHODS: Energy expenditure, heart rate, step
      rate, and perceived exertion were measured in 14 boys and 9 girls (ages 10-13
      years; BMI at 3-98th percentile for age and gender) while watching television at
      rest, playing DDR at 2 skill levels, playing Wii bowling and boxing, and walking
      at 2.6, 4.2, and 5.7 km/h. Arterial elasticity was measured at rest and
      immediately after gaming. RESULTS: Compared with watching television, energy
      expenditure while gaming or walking increased 2- to 3-fold. Similarly, high rates
      of energy expenditure, heart rate, and perceived exertion were elicited from
      playing Wii boxing, DDR level 2, or walking at 5.7 km/h. This occurred despite
      variations in step rate among activities, reflecting greater use of upper body
      during Wii play (lowest step rate) than during walking (highest step rate) or DDR
      play. Wii bowling and beginner level DDR elicited a 2-fold increase in energy
      expenditure compared to television watching. Large-artery elasticity declined
      immediately after both DDR and Wii. The change was inversely related to the
      increment in energy expenditure above rest achieved during the activity.
      CONCLUSIONS: Energy expenditure during active video game play is comparable to
      moderate-intensity walking. Thus, for children who spend considerable time
      playing electronic screen games for entertainment, physically active games seem
      to be a safe, fun, and valuable means of promoting energy expenditure.

PMID- 19596738
TI  - Outcomes in older patients after surgical treatment for hip fracture: a new
      approach to characterise the link between readmissions and the surgical stay.
AB  - BACKGROUND: in older patients, there is a high risk of hospital readmission
      within the first year after surgery for hip fracture, due to complications
      following treatment or to the evolution of prior comorbid conditions. OBJECTIVES:
      to identify factors associated with readmissions related to the index surgical
      stay. DESIGN: retrospective cohort study. SETTING: administrative claims
      databases. SUBJECTS: patients over 75 surgically treated for hip fracture in
      Paris area. METHODS: we analysed all admissions in 2005, and tracked for 1-year
      readmissions. First readmissions (FRs) were classified as related or unrelated to
      the index stay, according to rules defined a priori. We analysed the association
      between patient characteristics and the FR. RESULTS: among 5,709 patients, 32%
      had at least one readmission, 53% were FR related. Near 80% of related
      readmissions occurred within 3 months from discharge. Surgical conditions caused
      47% of all related readmissions, and male gender, dementia, cancer or kidney
      diseases were independent risks factors. CONCLUSIONS: half of readmissions could
      be classified as related to the index stay and a great majority of these occurred
      early post discharge. Surgical conditions caused 47% of all related readmissions.
      Improvement in orthopedic-geriatric co-care is suitable to expect an impact on
      outcomes after surgery.

PMID- 19596739
TI  - Muscle volume compared to cross-sectional area is more appropriate for evaluating
      muscle strength in young and elderly individuals.
AB  - OBJECTIVE: the present study examined which of muscle volume (MV) and cross
      sectional area (CSA) is appropriate for evaluating the relation with elbow flexor
      muscle strength in young and elderly individuals. METHODS: the subjects were 52
      young (20-34 year; 30 men and 22 women) and 51 elderly individuals (60-77 year,
      19 men and 32 women). The MV and maximal anatomical CSA (ACSA) of elbow flexors
      were determined by magnetic resonance imaging. The torque developed during
      maximal voluntary contraction of isometric elbow joint flexion was converted to
      force by dividing it by the forearm length of each subject. RESULTS: torque was
      significantly correlated with MV in young and elderly individuals (r = 0.564
      0.926). Similarly, force was also significantly correlated with ACSA in each of
      them (r = 0.637-0.906). However, the y-intercepts of the regression lines for the
      ACSA-force relationship in young men and women were significantly higher than
      zero. There was no age effect on torque per MV, whereas force per ACSA was
      significantly higher in young adults than in elderly individuals. CONCLUSION: for
      elbow flexors, MV compared to ACSA is appropriate for evaluating the size
      strength relationship and the existence of age-related difference in muscle
      strength per size.

PMID- 19596736
TI  - Predictors of clinical outcomes and hospital resource use of children after
      tracheotomy.
AB  - OBJECTIVES: The objectives are to describe health outcomes and hospital resource
      use of children after tracheotomy and identify patient characteristics that
      correlate with outcomes and hospital resource use. PATIENTS AND METHODS: A
      retrospective analysis of 917 children aged 0 to 18 years undergoing tracheotomy
      from 36 children's hospitals in 2002 with follow-up through 2007. Children were
      identified from ICD-9-CM tracheotomy procedure codes. Comorbid conditions
      (neurologic impairment [NI], chronic lung disease, upper airway anomaly,
      prematurity, and trauma) were identified with ICD-9-CM diagnostic codes. Patient
      characteristics were compared with in-hospital mortality, decannulation, and
      hospital resource use by using generalized estimating equations. RESULTS: Forty
      eight percent of children were <or=6 months old at tracheotomy placement. Chronic
      lung disease (56%), NI (48%), and upper airway anomaly (47%) were the most common
      underlying comorbid conditions. During hospitalization for tracheotomy placement,
      children with an upper airway anomaly experienced less mortality (3.3% vs 11.7%;
      P < .001) than children without an upper airway anomaly. Five years after
      tracheotomy, children with NI experienced greater mortality (8.8% vs 3.5%; P <or=
      .01), less decannulation (5.0% vs 11.0%; P <or= .01), and more total number of
      days in the hospital (mean [SE]: 39.5 [4.0] vs 25.6 [2.6] days; P <or= .01) than
      children without NI. These findings remained significant (P < .01) in
      multivariate analysis after controlling for other significant cofactors.
      CONCLUSIONS: Children with upper airway anomaly experienced less mortality, and
      children with NI experienced higher mortality rates and greater hospital resource
      use after tracheotomy. Additional research is needed to explore additional
      factors that may influence health outcomes in children with tracheotomy.

PMID- 19596740
TI  - A confusional state associated with use of lanthanum carbonate in a dialysis
      patient: a case report.
AB  - A 75-year-old woman was admitted with febrile confusion and abdominal pain. She
      was taking medications that included lanthanum carbonate. Examination, biology, a
      cerebral scan, and a review of her medications could not explain the confusion.
      The plain film of the abdomen revealed multiple diffuse calcium-like deposits
      throughout the digestive tract. The plasma levels of lanthanum were higher than
      normal. The confusion resolved after discontinuation of the lanthanum carbonate.
      This case raises the problem of the potential role played by lanthanum tablet
      residue in the genesis or aggravation of diverticular flare-up and the problem of
      the potential permeability of the blood-brain barrier with lanthanum use in case
      of its digestive accumulation, leading to increased serum concentrations.

PMID- 19596741
TI  - Optimizing haemodiafiltration: tools, strategy and remaining questions.

PMID- 19596742
TI  - Early histological changes in the kidney of people with morbid obesity.
AB  - BACKGROUND: Morbid obesity represents a major health problem with increasing
      incidence worldwide. The clinical manifestation of renal involvement in obesity
      is proteinuria, and the histological feature is glomerulomegaly with or without
      focal and segmental glomerulosclerosis (FSGS). In this study, we have
      investigated the very early histological changes in kidneys of people with morbid
      obesity and no proteinuria. Patients and methods. Eighteen patients with body
      mass index (BMI) >50 kg/m(2) who underwent a variant of biliopancreatic diversion
      with Roux-en-Y reconstruction (BPD-RYGBP) and consented to undergo a renal biopsy
      during the surgical procedure were included in the study. The estimation of early
      histological changes was performed on light (n = 18) and electron microscopy (n =
      13). RESULTS: The mean glomerular cross-sectional area was 30 943 +/- 10,984
      microm(2) that is higher than that observed in non-obese individuals. In 21% of
      the examined glomeruli, the glomerular planar surface area (GPSA) was >40,000
      microm(2). Thickening of the glomerular basement membrane (GBM) and scattered
      paramesangial deposits were identified in 9 of 13 patients (70%) whose renal
      tissue was examined by electron microscopy. A reduction in the slit pore
      frequency was observed in obese patients due to extensive foot process
      effacement. Significant positive correlations between mean GPSA and body weight
      (r = 0.462, P = 0.05), and between GBM thickness and HbA1c, serum total
      cholesterol and triglyceride levels (r = 0.60, P = 0.05; r = 0.789, P = 0.004; r
      = 0.70, P = 0.016, respectively), were observed. CONCLUSIONS: Glomerulomegaly as
      well as histological lesions resembling those of early diabetic nephropathy are
      observed in kidney biopsies of patients with morbid obesity even before the
      appearance of microalbuminuria. The potential regression of these changes after
      weight loss needs to be clarified.

PMID- 19596743
TI  - Cis-ruption mechanisms: disruption of cis-regulatory control as a cause of human
      genetic disease.
AB  - The spatiotemporally and quantitatively correct activity of a gene requires the
      presence of intact coding sequence as well as properly functioning regulatory
      control. One of the great challenges of the post-genome era is to gain a better
      understanding of the mechanisms of gene control. Proper gene regulation depends
      not only on the required transcription factors and associated complexes being
      present (in the correct dosage), but also on the integrity, chromatin
      conformation and nuclear positioning of the gene's chromosomal segment. Thus,
      when either the cis-trans regulatory system of a gene or the normal context of
      its chromatin structure are disrupted, gene expression may be adversely affected,
      potentially leading to disease. As transcriptional regulation is a highly complex
      process depending on many factors, there are many different mechanisms that can
      cause aberrant gene expression. Traditionally, the term 'position effect' was
      used to refer to situations where the level of expression of a gene is
      deleteriously affected by an alteration in its chromosomal environment, while
      maintaining an intact transcription unit. Over the past years, an ever increasing
      number of such disease-related position effect cases have come to light, and
      detailed studies have revealed insight into the variety of causes, which can be
      categorized into a number of different mechanistic groups. We suggest replacing
      the outdated term of 'position effect disease' with the new generic name of 'cis
      ruption disorder' to describe genetic disease cases that are caused by disruption
      of the normal cis-regulatory architecture of the disease gene locus. Here, we
      review these various cis-ruption mechanisms and discuss how their studies have
      contributed to our understanding of long- range gene regulation.

PMID- 19596744
TI  - The Budding Yeast "Saccharomyces cerevisiae" as a Drug Discovery Tool to Identify
      Plant-Derived Natural Products with Anti-Proliferative Properties.
AB  - The budding yeast Saccharomyces cerevisiae is a valuable system to study cell
      cycle regulation, which is defective in cancer cells. Due to the highly conserved
      nature of the cell-cycle machinery between yeast and humans, yeast studies are
      directly relevant to anticancer-drug discovery. The budding yeast is also an
      excellent model system for identifying and studying antifungal compounds because
      of the functional conservation of fungal genes. Moreover, yeast studies have also
      contributed greatly to our understanding of the biological targets and modes of
      action of bioactive compounds. Understanding the mechanism of action of
      clinically relevant compounds is essential for the design of improved second
      generation molecules. Here we describe our methodology for screening a library of
      plant-derived natural products in yeast in order to identify and characterize new
      compounds with anti-proliferative properties.

PMID- 19596746
TI  - Assessment of the Antioxidant and Reactive Oxygen Species Scavenging Activity of
      Methanolic Extract of Caesalpinia crista Leaf.
AB  - "Oxidative stress" is initiated by reactive oxygen species (ROS), which are
      responsible for majority of the diseases. However, antioxidants with ROS
      scavenging ability may have great relevance in the prevention of oxidative
      stress. The present study was undertaken, using a 70% methanolic extract of
      Caesalpinia crista leaves, to examine different in vitro tests in diversified
      fields including total antioxidant activity, scavenging activities for various
      ROS, iron chelating activity and phenolic and flavonoid contents. Total
      antioxidant activity was evaluated as trolox equivalent antioxidant capacity
      value of 0.546 +/- 0.014. The extract was investigated for different ROS
      scavenging activities and IC(50) values were found to be 0.44 +/- 0.1 mg/ml, 24.9
      +/- 0.98 MUg/ml, 33.72 +/- 0.85 MUg/ml, 61.13 +/- 3.24 MUg/mL and 170.51 +/- 4.68
      MUg/mL for hydroxyl, superoxide, nitric oxide, singlet oxygen and hypochlorous
      acid, respectively; however, no significant results were obtained in scavenging
      of hydrogen peroxide and peroxynitrite anion. The extract was found to be a
      potent iron chelator with IC(50) = 279.85 +/- 4.72 MUg/mL. The plant extract (100
      mg) yielded 50.23 +/- 0.003 mg/mL gallic acid equivalent phenolic content and
      106.83 +/- 0.0003 mg/mL quercetin equivalent flavonoid content. In the in vivo
      experiments, the extract treatment showed significant increase in the level of
      superoxide dismutase, catalase, glutathione-S-transferase and reduced
      glutathione. In a word, it may be concluded that 70% methanol extract of C.
      crista leaves acts as an antioxidant and ROS scavenger; which may be due to the
      presence of phenolic and flavonoid compounds.

PMID- 19596745
TI  - Traditional Medicinal Plant Extracts and Natural Products with Activity against
      Oral Bacteria: Potential Application in the Prevention and Treatment of Oral
      Diseases.
AB  - Oral diseases are major health problems with dental caries and periodontal
      diseases among the most important preventable global infectious diseases. Oral
      health influences the general quality of life and poor oral health is linked to
      chronic conditions and systemic diseases. The association between oral diseases
      and the oral microbiota is well established. Of the more than 750 species of
      bacteria that inhabit the oral cavity, a number are implicated in oral diseases.
      The development of dental caries involves acidogenic and aciduric Gram-positive
      bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal
      diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas
      gingivalis, Actinobacillus, Prevotella and Fusobacterium). Given the incidence of
      oral disease, increased resistance by bacteria to antibiotics, adverse affects of
      some antibacterial agents currently used in dentistry and financial
      considerations in developing countries, there is a need for alternative
      prevention and treatment options that are safe, effective and economical. While
      several agents are commercially available, these chemicals can alter oral
      microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth
      staining. Hence, the search for alternative products continues and natural
      phytochemicals isolated from plants used as traditional medicines are considered
      as good alternatives. In this review, plant extracts or phytochemicals that
      inhibit the growth of oral pathogens, reduce the development of biofilms and
      dental plaque, influence the adhesion of bacteria to surfaces and reduce the
      symptoms of oral diseases will be discussed further. Clinical studies that have
      investigated the safety and efficacy of such plant-derived medicines will also be
      described.

PMID- 19596747
TI  - The conquest of Wilson's disease.

PMID- 19596748
TI  - Gains of stopping smoking: portraits of the dialogue between public health
      promotion, art and design.

PMID- 19596749
TI  - Commentary: A continued affair with science and judgements.

PMID- 19596750
TI  - Sibship size, Helicobacter pylori infection and chronic atrophic gastritis: a
      population-based study among 9444 older adults from Germany.
AB  - BACKGROUND: Early-life social environment has been suggested to play an important
      role during the development of Helicobacter pylori-related gastric diseases. We
      aimed to assess the association of sibship size with H. pylori infection and
      chronic atrophic gastritis (CAG) in a population-based study from Germany.
      METHODS: In the baseline examination of ESTHER, a study conducted in Saarland,
      serological measurements of pepsinogen I and II and H. pylori antibodies were
      taken in 9444 participants aged 50-74 years. Information on potential risk
      factors and medical history were obtained by self-administered standardized
      questionnaire. RESULTS: A strong dose-response relationship between sibship size
      and H. pylori seroprevalence was observed (P < 0.01). Adjusted odds ratios (ORs)
      95% confidence interval (CI) for H. pylori seropositivity for subjects with 4, 5,
      6 and 7 or more siblings compared with subjects without siblings were 1.45 (1.20
      1.77), 1.83 (1.50-2.22) and 1.84 (1.47-2.31), respectively. A large sibship size
      was also associated with an increased risk of CAG with an adjusted OR of 1.42
      (1.01-2.01) for 7 or more compared with less than or equal to 2 siblings. This
      association was attenuated but not entirely eliminated after additional
      adjustment for H. pylori infection. Notably, a significant association between
      large sibship size and CAG was also found among H. pylori-negative subjects.
      CONCLUSIONS: Our results suggest that large sibship size is associated with
      increased H. pylori prevalence and CAG risk. The association with CAG risk may be
      mediated at least in part by H. pylori infection. However, mechanisms other than
      H. pylori infection may contribute to the 'sibling effect' as well.

PMID- 19596751
TI  - Long-term association of routine blood count (Coulter) variables on fatal
      coronary heart disease: 30-year results from the first prospective Northwick Park
      Heart Study (NPHS-I).
AB  - BACKGROUND: Since evidence of a long-term association between routine blood count
      (Coulter) variables and coronary heart disease (CHD) is inconsistent, the authors
      analysed white blood cell count (WBC), red blood cell count (RBC), haemoglobin
      (Hgb), packed cell volume (PCV) and platelet count for their long-term
      associations with CHD mortality in the first Northwick Park Heart Study (NPHS-I).
      NPHS-I has follow-up information for >30 years on 2167 White men and 941 White
      women and holds entry and follow-up data on haematological variables and other
      known CHD risk factors. METHODS: Proportional hazards Cox models were fitted to
      estimate rate ratios (RRs) for the separate and joint effects of entry and follow
      up Coulter variables. RESULTS: Entry RBC, PCV and Hgb were significant risk
      factors for CHD mortality after adjustment for gender but only PCV remained
      significant after adjustment for potential confounders [RR per 1 standard
      deviation (SD) increase = 1.17, 95% confidence interval (CI) 1.00-1.37]. This
      effect was partly reduced when the values of 6 years were analysed (RR per 1 SD
      increase = 1.10, 95% CI 0.93-1.30). No significant gender, smoking or age/time
      interactions were identified. PCV was the only significant predictor when all
      Coulter variables were studied jointly. CONCLUSION: PCV was found to predict CHD
      mortality even after controlling for classical risk factors. This may give some
      insight into possible mechanisms, such as an influence on thrombin production.

PMID- 19596758
TI  - Pulling the plug on ad hoc critical incident training.

PMID- 19596759
TI  - Seven misconceptions regarding volume therapy strategies--and their correction.

PMID- 19596760
TI  - Thrombelastography Platelet Mapping is a useful preoperative tool in surgical
      patients taking antiplatelet medication.

PMID- 19596761
TI  - Preoperative percutaneous patent foramen ovale closure before neurosurgery in the
      sitting position.

PMID- 19596762
TI  - Hyperbaric oxygen therapy for arterial gas embolism.

PMID- 19596763
TI  - Subanaesthetic sevoflurane by a helmet for bronchospasm after tracheal
      extubation.

PMID- 19596764
TI  - McGrath videolaryngoscope for an anticipated difficult airway.

PMID- 19596765
TI  - Retroperitoneal haematoma in a patient with continuous psoas compartment block
      and enoxaparin administration for total knee replacement.

PMID- 19596766
TI  - Mivacurium in patients with myasthenia gravis undergoing video-assisted
      thoracoscopic thymectomy.

PMID- 19596767
TI  - The racing-game effect: why do video racing games increase risk-taking
      inclinations?
AB  - The present studies investigated why video racing games increase players' risk
      taking inclinations. Four studies reveal that playing video racing games
      increases risk taking in a subsequent simulated road traffic situation, as well
      as risk-promoting cognitions and emotions, blood pressure, sensation seeking, and
      attitudes toward reckless driving. Study 1 ruled out the role of experimental
      demand in creating such effects. Studies 2 and 3 showed that the effect of
      playing video racing games on risk taking was partially mediated by changes in
      self-perceptions as a reckless driver. These effects were evident only when the
      individual played racing games that reward traffic violations rather than racing
      games that do not reward traffic violations (Study 3) and when the individual was
      an active player of such games rather than a passive observer (Study 4). In sum,
      the results underline the potential negative impact of racing games on traffic
      safety.

PMID- 19596768
TI  - Involvement of Toll-like receptors 2 and 4 in the innate immune response to
      Treponema denticola and its outer sheath components.
AB  - Treponema denticola is considered an important oral pathogen in the development
      and progression of periodontal diseases. In the present study, the mechanisms of
      recognition and activation of murine macrophages by T. denticola and its major
      outer sheath protein (MSP) and lipooligosaccharide (LOS or glycolipid) were
      investigated. T. denticola cells and the MSP induced innate immune responses
      through TLR2-MyD88, whereas LOS induced a macrophage response through TLR4-MyD88.
      The presence of gamma interferon (IFN-gamma), or of high numbers of T. denticola,
      circumvented the requirement for TLR2 for the macrophage response to T.
      denticola, although the response was still dependent on MyD88. In contrast,
      synergy with IFN-gamma did not alter the TLR dependence of the response to the T.
      denticola surface components LOS and MSP, despite enhanced sensitivity. These
      data suggest that although there is flexibility in the requirements for
      recognition of T. denticola cells (TLR2 dependent or independent), MyD88 is a
      requirement for the downstream signaling events that lead to inflammation. We
      also demonstrate that both outer sheath molecules LOS and MSP induce macrophage
      tolerance to further stimulation with enterobacterial lipopolysaccharide.
      Tolerance induced by T. denticola components during mixed infections may
      represent a general mechanism through which bacteria evade clearance.

PMID- 19596769
TI  - Clinical chemistry of congenic mice with quantitative trait loci for predicted
      responses to Trypanosoma congolense infection.
AB  - Trypanosoma congolense is a protozoan parasite that causes severe diseases in
      livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control
      the survival time of mice after infection with T. congolense. Congenic mice
      carrying the C57BL/6 resistance alleles on the A/J background were developed for
      each of these loci. The congenic mice were used to physically map the regions
      containing the QTL gene(s) and to investigate the physiological effect of each
      locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were
      obtained for 15 analytes at five time points. Congenic mice were assessed for
      survival, parasitemia, and anemia as well as seven clinical-chemical analytes.
      The survival times were significantly increased in the Tir1 and Tir2 mice but not
      Tir3 congenic mice. The survival time of the parental inbred mice correlated
      negatively with parasitemia but positively with alanine aminotransferase
      activities in serum, suggesting that inflammatory reactions in the liver had a
      beneficial effect possibly associated with reduced parasitemia. However, there
      was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2
      congenic mice relative to their controls, showing that survival, parasitemia, and
      degree of liver damage are not associated with each other, despite the
      correlation in the parental lines. These data suggest that the congenic loci
      affect survival but do not affect control of parasite number. They may therefore
      act by limiting the pathological consequences of T. congolense infection.

PMID- 19596770
TI  - Toll-like receptor 5-dependent regulation of inflammation in systemic Salmonella
      enterica Serovar typhimurium infection.
AB  - Salmonella enterica, a gram-negative pathogen, causes a spectrum of human
      infections including enterocolitis and typhoid fever. We previously showed that
      Salmonella flagellin played a role in suppressing intestinal mucosal inflammation
      in a murine model of acute enterocolitis. In this study, we examined the role of
      flagellin in the typhoid-like systemic murine Salmonella infection by measuring
      bacterial proliferation, inflammation, leukocyte recruitment, and cellular
      apoptosis in Peyer's patches (PPs), mesenteric lymph node (MLN), and spleen. We
      found that relative to an isogenic wild-type (WT) strain, aflagellate Salmonella
      exhibited increased proliferation at 4 days postinfection in PPs and MLN but not
      spleen. The aflagellate mutant also elicited increased local and systemic
      secretion of inflammatory cytokines such as interleukin-1beta, gamma interferon,
      and tumor necrosis factor alpha and enhanced surface expression of ICAM-1 on
      macrophages and dendritic cells (DCs). Furthermore, the recruitment of
      macrophages and DCs in PPs and MLN, but not spleen, was enhanced upon infection
      with aflagellate Salmonella. The relative differences between WT and aflagellate
      Salmonella were highly attenuated in Toll-like receptor 5-deficient (TLR5(-/-))
      mice, indicating involvement of TLR5-dependent signaling. Interestingly,
      infection with the aflagellate mutant also resulted in decreased levels of T-cell
      apoptosis in PPs relative to infection with WT Salmonella. We postulate that the
      initial lack of detection of the aflagellate mutant in the mucosa permits
      increased proliferation within the host and enhances inflammatory signaling in
      nonepithelial cell types, which subsequently promotes leukocyte recruitment. In
      contrast, lack of difference in any disease parameter measured in the spleen
      likely reflects that Salmonella expression of flagellin is downregulated in this
      organ. Thus, the characteristic inflammatory pathology of Salmonella infection
      occurs only in PPs and to a lesser extent in MLN during the initial phases of
      infection and these early responses are dependent on TLR5.

PMID- 19596771
TI  - Anaplasma phagocytophilum dense-cored organisms mediate cellular adherence
      through recognition of human P-selectin glycoprotein ligand 1.
AB  - Anaplasma phagocytophilum is an obligate intracellular bacterium that infects
      granulocytes to cause human granulocytic anaplasmosis. The susceptibilities of
      human neutrophils and promyelocytic HL-60 cells to A. phagocytophilum are linked
      to bacterial usage of P-selectin glycoprotein ligand 1 (PSGL-1) as a receptor for
      adhesion and entry. A. phagocytophilum undergoes a biphasic developmental cycle,
      transitioning between a smaller electron dense-cored cell (DC), which has a dense
      nucleoid, and a larger, pleomorphic electron lucent reticulate cell (RC), which
      has a dispersed nucleoid. The pathobiological roles of each form have not been
      elucidated. To ascertain the role of each form, we used electron microscopy to
      monitor bacterial binding, entry, and intracellular development within HL-60
      cells. Only DCs were observed binding to and inducing uptake by HL-60 cells. By
      12 h, internalized DCs had transitioned to RCs, which had initiated replication.
      By 24 h, large RC numbers were observed within individual inclusions. Reinfection
      had occurred by 36 h, as individual, vacuole-enclosed DCs and RCs were again
      observed. The abilities of DC- and RC-enriched A. phagocytophilum populations to
      bind and/or infect HL-60 cells or Chinese hamster ovary cells transfected to
      express PSGL-1 (PSGL-1 CHO) were compared. Only DCs bound PSGL-1 CHO cells and
      did so in a PSGL-1-blocking antibody-inhibitable manner. These results
      demonstrate that the respective roles of A. phagocytophilum DCs and RCs are
      consistent with analogous forms of other obligate intracellular pathogens that
      undergo biphasic development and hint that the PSGL-1-targeting adhesin(s) may be
      upregulated or optimally posttranslationally modified on DCs.

PMID- 19596772
TI  - CT043, a protective antigen that induces a CD4+ Th1 response during Chlamydia
      trachomatis infection in mice and humans.
AB  - Despite several decades of intensive studies, no vaccines against Chlamydia
      trachomatis, an intracellular pathogen causing serious ocular and urogenital
      diseases, are available yet. Infection-induced immunity in both animal models and
      humans strongly supports the notion that for a vaccine to be effective a strong
      CD4(+) Th1 immune response should be induced. In the course of our vaccine
      screening program based on the selection of chlamydial proteins eliciting cell
      mediated immunity, we have found that CT043, a protein annotated as hypothetical,
      induces CD4(+) Th1 cells both in chlamydia-infected mice and in human patients
      with diagnosed C. trachomatis genital infection. DNA priming/protein boost
      immunization with CT043 results in a 2.6-log inclusion-forming unit reduction in
      the murine lung infection model. Sequence analysis of CT043 from C. trachomatis
      human isolates belonging to the most representative genital serovars revealed a
      high degree of conservation, suggesting that this antigen could provide cross
      serotype protection. Therefore, CT043 is a promising vaccine candidate against C.
      trachomatis infection.

PMID- 19596773
TI  - Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals
      defects in central metabolism and surface proteins.
AB  - Comparative genomic analysis of a wild-type strain of the ovine pathogen
      Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive,
      virulence-attenuated live vaccine derivative identified 22 single nucleotide
      polymorphisms unique to the mutant, including nine nonsynonymous mutations, one
      leading to a truncation of pmpG, which encodes a polymorphic membrane protein,
      and two intergenic mutations potentially affecting promoter sequences. Other
      nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding
      sequences encoding a putative lipoprotein, a sigma-54-dependent response
      regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases,
      and a putative serine hydroxymethyltransferase. One of the intergenic mutations
      putatively affects transcription of two divergent genes encoding pyruvate kinase
      and a putative SOS response nuclease, respectively. These observations suggest
      that the temperature-sensitive phenotype and associated virulence attenuation of
      the vaccine strain result from disrupted metabolic activity due to altered
      pyruvate kinase expression and/or alteration in the function of one or more
      membrane proteins, most notably PmpG and a putative lipoprotein.

PMID- 19596774
TI  - Shiga toxin 1-induced proinflammatory cytokine production is regulated by the
      phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling
      pathway.
AB  - Shiga toxin 1 (Stx1) transiently increases the expression of proinflammatory
      cytokines by macrophage-like THP-1 cells in vitro. Increased cytokine production
      is partly due to activation of the translation initiation factor eIF4E through a
      mitogen-activated protein kinase (MAPK)- and Mnk1-dependent pathway. eIF4E
      availability for translation initiation is regulated by association with eIF4E
      binding proteins (4E-BP). In this study, we showed that Stx1 transiently induced
      4E-BP hyperphosphorylation, which may release eIF4E for translation initiation.
      Phosphorylation of 4E-BP at priming sites T37 and T46 was not altered by Stx1 but
      was transiently increased at S65, concomitant with increased cytokine expression.
      Using kinase inhibitors, we showed that 4E-BP phosphorylation was dependent on
      phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin
      (mTOR) activation but did not require MAPKs. Stx1 treatment resulted in increased
      levels of cytosolic Ca(2+). PI3K and Akt activation led to the phosphorylation
      and inactivation of the positive cytokine regulator glycogen synthase kinase
      3alpha/beta (GSK-3alpha/beta). PI3K, Akt, and mTOR inhibitors and small
      interfering RNA knockdown of Akt expression all increased, whereas a GSK
      3alpha/beta inhibitor decreased, Stx1-induced soluble tumor necrosis factor alpha
      and interleukin-1beta production. Overall, these findings suggest that despite
      transient activation of 4E-BP, the PI3K/Akt/mTOR pathway negatively influences
      cytokine induction by inactivating the positive regulator GSK-3alpha/beta.

PMID- 19596776
TI  - Mechanistic science.

PMID- 19596775
TI  - The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation
      of caspase-1 via induction of potassium ion efflux in infected macrophages.
AB  - A genomic locus called "region of difference 1" (RD1) in Mycobacterium
      tuberculosis has been shown to contribute to the generation of host protective
      immunity as well as to the virulence of the bacterium. To gain insight into the
      molecular mechanism, we investigated the difference in the cytokine-inducing
      ability between H37Rv and a mutant strain deficient for RD1 (DeltaRD1). We found
      that RD1 is implicated in the production of caspase-1-dependent cytokines,
      interleukin-18 (IL-18) and IL-1beta, from infected macrophages. The expression of
      these cytokines was similarly induced after infection with H37Rv and DeltaRD1.
      However, the activation of caspase-1 was observed only in H37Rv-infected
      macrophages. The cytokine production and caspase-1 activation were induced
      independently of type I interferon receptor signaling events. We also found that
      the activation of caspase-1 was markedly inhibited with increasing concentrations
      of extracellular KCl. Furthermore, the production of IL-18 and IL-1beta and
      caspase-1 activation were induced independently of a P2X7 purinergic receptor,
      and the inability of DeltaRD1 in caspase-1 activation was compensated for by
      nigericin, an agent inducing the potassium ion efflux. Based on these results, we
      concluded that RD1 participates in caspase-1-dependent cytokine production via
      induction of the potassium ion efflux in infected macrophages.

PMID- 19596777
TI  - Staphylococcus aureus induces microglial inflammation via a glycogen synthase
      kinase 3beta-regulated pathway.
AB  - A proinflammatory role for glycogen synthase kinase 3beta (GSK-3beta) has been
      demonstrated. Here, we addressed its roles on heat-inactivated Staphylococcus
      aureus-induced microglial inflammation. Heat-inactivated S. aureus induced tumor
      necrosis factor alpha (TNF-alpha) and nitric oxide (NO) production, at least in
      part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-alpha
      largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus
      activated GSK-3beta, and inhibiting GSK-3beta reduced TNF-alpha production as
      well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF
      kappaB was essential for heat-inactivated S. aureus-induced TNF-alpha and NO,
      inhibiting GSK-3beta blocked heat-inactivated S. aureus-induced NF-kappaB p65
      nuclear translocation. Additionally, inhibiting GSK-3beta enhanced heat
      inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti
      inflammatory cytokine which inhibits TNF-alpha production). Neutralization of IL
      10 reduced TNF-alpha downregulation caused by GSK-3beta inhibition. These results
      suggest that GSK-3beta regulates heat-inactivated S. aureus-induced TNF-alpha and
      NO production in microglia mainly by activating NF-kappaB and probably by
      inhibiting IL-10.

PMID- 19596778
TI  - BAR domain proteins Rvs161 and Rvs167 contribute to Candida albicans endocytosis,
      morphogenesis, and virulence.
AB  - The Candida albicans plasma membrane plays critical roles in growth and virulence
      and as a target for antifungal drugs. Three C. albicans genes that encode Bin
      Amphiphysin-Rvs homology domain proteins were mutated to define their roles in
      plasma membrane function. The deletion of RVS161 and RVS167, but not RVS162,
      caused strong defects. The rvs161Delta mutant was more defective in endocytosis
      and morphogenesis than rvs167Delta, but both were strongly defective in
      polarizing actin patches. Other plasma membrane constituents were still properly
      localized, including a filipin-stained domain at the hyphal tips. An analysis of
      growth under different in vitro conditions showed that the rvs161Delta and
      rvs167Delta mutants grew less invasively in agar and also suggested that they
      have defects in cell wall synthesis and Rim101 pathway signaling. These mutants
      were also more resistant to the antimicrobial peptide histatin 5 but showed
      essentially normal responses to the drugs caspofungin and amphotericin.
      Surprisingly, the rvs161Delta mutant was more sensitive to fluconazole, whereas
      the rvs167Delta mutant was more resistant, indicating that these mutations cause
      overlapping but distinct effects on cells. The rvs161Delta and rvs167Delta
      mutants both showed greatly reduced virulence in mice. However, the mutants were
      capable of growing to high levels in kidneys. Histological analyses of infected
      kidneys revealed that these rvsDelta mutants grew in a large fungal mass that was
      walled off by leukocytes, rather than forming disseminated microabscesses as seen
      for the wild type. The diminished virulence is likely due to a combination of the
      morphogenesis defects that reduce invasive growth and altered cell wall
      construction that exposes proinflammatory components to the host immune system.

PMID- 19596779
TI  - Role of the type III secretion system in a hypervirulent lineage of Bordetella
      bronchiseptica.
AB  - Despite the fact that closely related bacteria can cause different levels of
      disease, the genetic changes that cause some isolates to be more pathogenic than
      others are generally not well understood. We use a combination of approaches to
      determine which factors contribute to the increased virulence of a Bordetella
      bronchiseptica lineage. A strain isolated from a host with B. bronchiseptica
      induced disease, strain 1289, was 60-fold more virulent in mice than one isolated
      from an asymptomatically infected host, strain RB50. Transcriptome analysis and
      quantitative reverse transcription-PCR showed that the type III secretion system
      (TTSS) genes were more highly expressed by strain 1289 than strain RB50. Compared
      to strain RB50, strain 1289 exhibited greater TTSS-mediated cytotoxicity of a
      mammalian cell line. Additionally, we show that the increase in virulence of
      strain 1289 compared to that of RB50 was partially attributable to the TTSS.
      Using multilocus sequence typing, we identified another strain from the same
      lineage as strain 1289. Similar to strain 1289, we implicate the TTSS in the
      increased virulence of this strain. Together, our data suggest that the TTSS is
      involved in the increased virulence of a B. bronchiseptica lineage which appears
      to be disproportionately associated with disease. These data are consistent with
      the view that B. bronchiseptica lineages can have different levels of virulence,
      which may contribute to this species' ability to cause different severities of
      respiratory disease.

PMID- 19596780
TI  - Cellular responses to mycobacterial antigens are present in bronchoalveolar
      lavage fluid used in the diagnosis of sarcoidosis.
AB  - Considerable evidence supports the concept that CD4(+) T cells are important in
      sarcoidosis pathogenesis, but the antigens responsible for the observed Th1
      immunophenotype remain elusive. The epidemiologic association with bioaerosols
      and the presence of granulomatous inflammation support consideration of
      mycobacterial antigens. To explore the role of mycobacterial antigens in
      sarcoidosis immunopathogenesis, we assessed the immune recognition of
      mycobacterial antigens, the 6-kDa early secreted antigenic protein (ESAT-6) and
      catalase-peroxidase (KatG), by T cells derived from bronchoalveolar lavage (BAL)
      fluid obtained during diagnostic bronchoscopy. We report the presence of antigen
      specific recognition of ESAT-6 and KatG in T cells from BAL fluid of 32/44
      sarcoidosis subjects, compared to 1/27 controls (P < 0.0001). CD4(+) T cells were
      primarily responsible for immune recognition (32/44 sarcoidosis subjects),
      although CD8(+) T-cell responses were observed (25/41 sarcoidosis subjects).
      Recognition was significantly absent from BAL fluid cells of patients with other
      lung diseases, including infectious granulomatous diseases. Blocking of Toll-like
      receptor 2 reduced the strength of the observed immune response. The presence of
      immune responses to mycobacterial antigens in cells from BAL fluid used for
      sarcoidosis diagnosis suggests a strong association between mycobacteria and
      sarcoidosis pathogenesis. Inhibition of immune recognition with monoclonal
      antibody against Toll-like receptor 2 suggests that induction of innate immunity
      by mycobacteria contributes to the polarized Th1 immune response.

PMID- 19596781
TI  - Regulation of aurora B expression by the bromodomain protein Brd4.
AB  - The bromodomain protein Brd4 plays critical roles in cellular proliferation and
      cell cycle progression. In this study, we investigated the involvement of Brd4 in
      cell cycle regulation and observed aberrant chromosome segregation and failures
      in cytokinesis in cancer cells as well as in primary keratinocytes in which Brd4
      has been knocked down by RNA interference. Suppression of Brd4 protein levels in
      proliferating cells decreased Aurora B protein and transcript levels and
      abolished its chromosomal distribution. In contrast, exogenous Brd4 expression
      stimulated Aurora B promoter reporter activity and upregulated endogenous Aurora
      B expression. Aurora B kinase is a chromosomal passenger protein that is
      essential for chromosome segregation and cytokinesis. Either overexpression of
      Aurora B or its inactivation can induce defects in centrosome function, spindle
      assembly, chromosome alignment, and cytokinesis in various cancer cells. The
      impaired regulation of Aurora B expression in human cells by Brd4 knockdown or
      overexpression coincided with mitotic catastrophe and multinucleation that are
      typically observed when Aurora B is inactivated or overexpressed. Overall, our
      data suggest that Brd4 is essential for the maintenance of the cell cycle
      progression mediated at least in part through the control of transcription of the
      Aurora B kinase cell cycle regulatory gene.

PMID- 19596783
TI  - The multiple endocrine neoplasia type 1 (MEN1) tumor suppressor regulates
      peroxisome proliferator-activated receptor gamma-dependent adipocyte
      differentiation.
AB  - Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor
      suppressor gene, is involved in activation of gene transcription as part of an
      MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which
      harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1
      patients frequently develop lipomas and peroxisome proliferator-activated
      receptor gamma (PPARgamma) is expressed in several MEN1-related tumor types, we
      investigated regulation of PPARgamma activity by menin. We found that menin is
      required for adipocyte differentiation of murine 3T3-L1 cells and PPARgamma
      expressing mouse embryonic fibroblasts. Menin augments PPARgamma target gene
      expression through recruitment of H3K4 methyltransferase activity. Menin
      interacts directly with the activation function 2 transcription activation domain
      of PPARgamma in a ligand-independent fashion. Ligand-dependent coactivation,
      however, is dependent on the LXXLL motif of menin and the intact helix 12 of
      PPARgamma. We propose that menin is an important factor in PPARgamma-mediated
      adipogenesis and that loss of PPARgamma function may contribute to lipoma
      development in MEN1 patients.

PMID- 19596782
TI  - Two GW repeat proteins interact with Tetrahymena thermophila argonaute and
      promote genome rearrangement.
AB  - In conjugating Tetrahymena thermophila, massive DNA elimination occurs upon the
      development of the new somatic genome from the germ line genome. Small,
      approximately 28-nucleotide scan RNAs (scnRNAs) and Twi1p, an Argonaute family
      member, mediate H3K27me3 and H3K9me3 histone H3 modifications, which lead to
      heterochromatin formation and the excision of the heterochromatinized germ line
      limited sequences. In our search for new factors involved in developmental DNA
      rearrangement, we identified two Twi1p-interacting proteins, Wag1p and CnjBp.
      Both proteins contain GW (glycine and tryptophan) repeats, which are
      characteristic of several Argonaute-interacting proteins in other organisms.
      Wag1p and CnjBp colocalize with Twi1p in the parental macronucleus early in
      conjugation and in the new developing macronucleus during later developmental
      stages. Around the time DNA elimination occurs, Wag1p forms multiple nuclear
      bodies in the developing macronuclei that do not colocalize with heterochromatic
      DNA elimination structures. Analyses of DeltaWAG1, DeltaCnjB, and double
      DeltaWAG1 DeltaCnjB knockout strains revealed that WAG1 and CnjB genes need to be
      deleted together to inhibit the downregulation of specific scnRNAs, the formation
      of DNA elimination structures, and DNA excision. Thus, Wag1p and CnjBp are two
      novel players with overlapping functions in RNA interference-mediated genome
      rearrangement in Tetrahymena.

PMID- 19596784
TI  - Arginine methylation regulates telomere length and stability.
AB  - TRF2, a component of the shelterin complex, functions to protect telomeres. TRF2
      contains an N-terminal basic domain rich in glycines and arginines, similar to
      the GAR motif that is methylated by protein arginine methyltransferases. However,
      whether arginine methylation regulates TRF2 function has not been determined.
      Here we report that amino acid substitutions of arginines with lysines in the
      basic domain of TRF2 induce telomere dysfunction-induced focus formation, leading
      to induction of cellular senescence. We have demonstrated that cells
      overexpressing TRF2 lysine mutants accumulate telomere doublets, indicative of
      telomere instability. We uncovered that TRF2 interacts with PRMT1, and its
      arginines in the basic domain undergo PRMT1-mediated methylation both in vitro
      and in vivo. We have shown that loss of PRMT1 induces growth arrest in normal
      human cells but has no effect on cell proliferation in cancer cells, suggesting
      that PRMT1 may control cell proliferation in a cell type-specific manner. We
      found that depletion of PRMT1 in normal human cells results in accumulation of
      telomere doublets, indistinguishable from overexpression of TRF2 lysine mutants.
      PRMT1 knockdown in cancer cells upregulates TRF2 association with telomeres,
      promoting telomere shortening. Taken together, these results suggest that PRMT1
      may control telomere length and stability in part through TRF2 methylation.

PMID- 19596785
TI  - The concerted action of Msh2 and UNG stimulates somatic hypermutation at A . T
      base pairs.
AB  - Mismatch repair plays an essential role in reducing the cellular mutation load.
      Paradoxically, proteins in this pathway produce A . T mutations during the
      somatic hypermutation of immunoglobulin genes. Although recent evidence
      implicates the translesional DNA polymerase eta in producing these mutations, it
      is unknown how this or other translesional polymerases are recruited to
      immunoglobulin genes, since these enzymes are not normally utilized in
      conventional mismatch repair. In this report, we demonstrate that A . T mutations
      were closely associated with transversion mutations at a deoxycytidine.
      Furthermore, deficiency in uracil-N-glycolase (UNG) or mismatch repair reduced
      this association. These data reveal a previously unknown interaction between the
      base excision and mismatch repair pathways and indicate that an abasic site
      generated by UNG within the mismatch repair tract recruits an error-prone
      polymerase, which then introduces A . T mutations. Our analysis further indicates
      that repair tracts typically are approximately 200 nucleotides long and that
      polymerase eta makes approximately 1 error per 300 T nucleotides. The concerted
      action of Msh2 and UNG in stimulating A . T mutations also may have implications
      for mutagenesis at sites of spontaneous cytidine deamination.

PMID- 19596786
TI  - ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing
      effects on the mammary epithelium in vivo.
AB  - Data concerning the prognostic value of ErbB4 in breast cancer and effects on
      cell growth have varied in published reports, perhaps due to the unknown
      signaling consequences of expression of the intracellular proteolytic ErbB4
      s80(HER4) fragment or due to differing signaling capabilities of alternatively
      spliced ErbB4 isoforms. One isoform (Cyt1) contains a 16-residue intracellular
      sequence that is absent from the other (Cyt2). We expressed s80(Cyt1) and
      s80(Cyt2) in HC11 mammary epithelial cells, finding diametrically opposed effects
      on the growth and organization of colonies in three-dimensional matrices. Whereas
      expression of s80(Cyt1) decreased growth and increased the rate of three
      dimensional lumen formation, that of s80(Cyt2) increased proliferation without
      promoting lumen formation. These results were recapitulated in vivo, using
      doxycycline-inducible, mouse breast-transgenic expression of s80(Cyt1) amd
      s80(Cyt2). Expression of s80(Cyt1) decreased growth of the mammary ductal
      epithelium, caused precocious STAT5a activation and lactogenic differentiation,
      and increased cell surface E-cadherin levels. Remarkably, ductal growth
      inhibition by s80(Cyt1) occurred simultaneously with lobuloalveolar growth that
      was unimpeded by s80(Cyt1), suggesting that the response to ErbB4 may be
      influenced by the epithelial subtype. In contrast, expression of s80(Cyt2) caused
      epithelial hyperplasia, increased Wnt and nuclear beta-catenin expression, and
      elevated expression of c-myc and cyclin D1 in the mammary epithelium. These
      results demonstrate that the Cyt1 and Cyt2 ErbB4 isoforms, differing by only 16
      amino acids, exhibit markedly opposing effects on mammary epithelium growth and
      differentiation.

PMID- 19596787
TI  - A Cds1-mediated checkpoint protects the MBF activator Rep2 from ubiquitination by
      anaphase-promoting complex/cyclosome-Ste9 at S-phase arrest in fission yeast.
AB  - Transcription of the MluI cell cycle box (MCB) motif-containing genes at G(1)
      phase is regulated by the MCB-binding factors (MBF) (also called DSC1) in
      Schizosaccharomyces pombe. Upon S-phase arrest, the MBF transcriptional activity
      is induced through the accumulation of the MBF activator Rep2. In this study, we
      show that the turnover of Rep2 is attributable to ubiquitin-mediated proteolysis.
      Levels of Rep2 oscillate during the cell cycle, with a peak at G(1) phase,
      coincident with the MBF activity. Furthermore, we show that Rep2 ubiquitination
      requires the function of the E3 ligase anaphase-promoting complex/cyclosome
      (APC/C). Ste9 can be phosphorylated by the checkpoint kinase Cds1 in vitro, and
      its inhibition/phosphorylation at S-phase arrest is dependent on the function of
      Cds1. Our data indicate that the Cds1-dependent stabilization of Rep2 is achieved
      through the inhibition/phosphorylation of APC/C-Ste9 at the onset of S-phase
      arrest. Stabilization of Rep2 is important for stimulating transcription of the
      MBF-dependent genes to ensure a sufficient supply of proteins essential for cell
      recovery from S-phase arrest. We propose that oscillation of Rep2 plays a role in
      regulation of periodic transcription of the MBF-dependent genes during cell cycle
      progression.

PMID- 19596788
TI  - The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic
      nutrient homeostasis.
AB  - We used a Cre-loxP approach to generate mice with varied expression of hepatic
      Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient
      homeostasis. While nutrient-sensitive transcripts were expressed nearly normally
      in liver lacking Irs2 (LKO2 mice), these transcripts were significantly
      dysregulated in liver lacking Irs1 (LKO1 mice) or Irs1 and Irs2 together (DKO
      mice). Similarly, a set of key gluconeogenic and lipogenic genes was regulated
      nearly normally by feeding in liver retaining a single Irs1 allele without Irs2
      (DKO/1 mice) but was poorly regulated in liver retaining one Irs2 allele without
      Irs1 (DKO/2 mice). DKO/2 mice, but not DKO/1 mice, also showed impaired glucose
      tolerance and insulin sensitivity-though both Irs1 and Irs2 were required to
      suppress hepatic glucose production during hyperinsulinemic-euglycemic clamp. In
      contrast, either hepatic Irs1 or Irs2 mediated suppression of HGP by
      intracerebroventricular insulin infusion. After 12 weeks on a high-fat diet,
      postprandial tyrosine phosphorylation of Irs1 increased in livers of control and
      LKO2 mice, whereas tyrosine phosphorylation of Irs2 decreased in control and LKO1
      mice. Moreover, LKO1 mice -- but not LKO2 mice -- that were fed a high-fat diet
      developed postprandial hyperglycemia. We conclude that Irs1 is the principal
      mediator of hepatic insulin action that maintains glucose homeostasis.

PMID- 19596789
TI  - The tumor suppressor functions of p27(kip1) include control of the
      mesenchymal/amoeboid transition.
AB  - In many human cancers, p27 downregulation correlates with a worse prognosis,
      suggesting that p27 levels could represent an important determinant in cell
      transformation and cancer development. Using a mouse model system based on v-src
      induced transformation, we show here that p27 absence is always linked to a more
      aggressive phenotype. When cultured in three-dimensional contexts, v-src
      transformed p27-null fibroblasts undergo a morphological switch from an elongated
      to a rounded cell shape, accompanied by amoeboid-like morphology and motility.
      Importantly, the acquisition of the amoeboid motility is associated with a
      greater ability to move and colonize distant sites in vivo. The reintroduction of
      different p27 mutants in v-src-transformed p27-null cells demonstrates that the
      control of cell proliferation and motility represents two distinct functions of
      p27, both necessary for it to fully act as a tumor suppressor. Thus, we highlight
      here a new p27 function in driving cell plasticity that is associated with its C
      terminal portion and does not depend on the control of cyclin-dependent kinase
      activity.

PMID- 19596790
TI  - Kinase-independent functions of TEL1 in telomere maintenance.
AB  - TEL1 is important in Saccharomyces cerevisiae telomere maintenance, and its
      kinase activity is required. Tel1p associates with telomeres in vivo, is enriched
      at short telomeres, and enhances the binding of telomerase components to short
      telomeres. However, it is unclear how the kinase activity and telomere
      association contribute to Tel1p's overall function in telomere length
      maintenance. To investigate this question, we generated a set of single point
      mutants and a double point mutant (tel1(KD)) of Tel1p that were kinase deficient
      and two Xrs2p mutants that failed to bind Tel1p. Using these separation-of
      function alleles in a de novo telomere elongation assay, we found, surprisingly,
      that the tel1(KD) allele and xrs2 C-terminal mutants were both partially
      functional. Combining the tel1(KD) and xrs2 C-terminal mutants had an additive
      effect and resembled the TEL1 null (tel1Delta) phenotype. These data indicate
      that Tel1p has two separate functions in telomere maintenance and that the Xrs2p
      dependent recruitment of Tel1p to telomeres plays an important role even in the
      absence of its kinase activity.

PMID- 19596791
TI  - Coupling phosphate homeostasis to cell cycle-specific transcription: mitotic
      activation of Saccharomyces cerevisiae PHO5 by Mcm1 and Forkhead proteins.
AB  - Cells devote considerable resources to nutrient homeostasis, involving nutrient
      surveillance, acquisition, and storage at physiologically relevant
      concentrations. Many Saccharomyces cerevisiae transcripts coding for proteins
      with nutrient uptake functions exhibit peak periodic accumulation during M phase,
      indicating that an important aspect of nutrient homeostasis involves
      transcriptional regulation. Inorganic phosphate is a central macronutrient that
      we have previously shown oscillates inversely with mitotic activation of PHO5.
      The mechanism of this periodic cell cycle expression remains unknown. To date,
      only two sequence-specific activators, Pho4 and Pho2, were known to induce PHO5
      transcription. We provide here evidence that Mcm1, a MADS-box protein, is
      essential for PHO5 mitotic activation. In addition, we found that cells
      simultaneously lacking the forkhead proteins, Fkh1 and Fkh2, exhibited a 2.5-fold
      decrease in PHO5 expression. The Mcm1-Fkh2 complex, first shown to transactivate
      genes within the CLB2 cluster that drive G(2)/M progression, also associated
      directly at the PHO5 promoter in a cell cycle-dependent manner in chromatin
      immunoprecipitation assays. Sds3, a component specific to the Rpd3L histone
      deacetylase complex, was also recruited to PHO5 in G(1). These findings provide
      (i) further mechanistic insight into PHO5 mitotic activation, (ii) demonstrate
      that Mcm1-Fkh2 can function combinatorially with other activators to yield late
      M/G(1) induction, and (iii) couple the mitotic cell cycle progression machinery
      to cellular phosphate homeostasis.

PMID- 19596792
TI  - Mechanoregulation of proliferation.
AB  - The proliferation of all nontransformed adherent cells is dependent upon the
      development of mechanical tension within the cell; however, little is known about
      the mechanisms by which signals regulated by mechanical tension are integrated
      with those regulated by growth factors. We show here that Skp2, a component of a
      ubiquitin ligase complex that mediates the degradation of several proteins that
      inhibit proliferation, is upregulated when increased mechanical tension develops
      in intact smooth muscle and that its upregulation is critical for the smooth
      muscle proliferative response to increased mechanical tension. Notably, whereas
      growth factors regulate Skp2 at the level of protein stability, we found that
      mechanical tension regulates Skp2 at the transcriptional level. Importantly, we
      demonstrate that the calcium-regulated transcription factor NFATc1 is a critical
      mediator of the effect of increased mechanical tension on Skp2 transcription.
      These findings identify Skp2 as a node at which signals from mechanical tension
      and growth factors are integrated to regulate proliferation, and they define
      calcium-NFAT-Skp2 signaling as a critical pathway in the mechanoregulation of
      proliferation.

PMID- 19596793
TI  - Corneodesmosin gene ablation induces lethal skin-barrier disruption and hair
      follicle degeneration related to desmosome dysfunction.
AB  - Corneodesmosin (CDSN) is specific to desmosomes of epithelia undergoing
      cornification, mainly the epidermis and the inner root sheath of the hair
      follicles. CDSN nonsense mutations are associated with hypotrichosis simplex of
      the scalp, a rare disease that leads to complete baldness in young adults. CDSN
      displays adhesive properties, mostly attributable to its N-terminal glycine-rich
      domain, and is sequentially proteolyzed as corneocytes migrate towards the skin
      surface. K14-promoter driven Cre-mediated deletion of Cdsn in mice resulted in
      neonatal death as a result of epidermal tearing upon minor mechanical stress.
      Ultrastructural analyses revealed a desmosomal break at the interface between the
      living and cornified layers. After grafting onto nude mice, knockout skin showed
      a chronic defect in the epidermal permeability barrier. The epidermis was first
      hyperproliferative with a thick cornified layer, then, both the epidermis and the
      hair follicles degenerated. In adults, Cdsn deletion resulted in similar
      histological abnormalities and in a lethal barrier defect. We demonstrate that
      Cdsn is not essential for skin-barrier formation in utero, but is vital
      throughout life to preserve this barrier by maintaining desmosome integrity. The
      strong adhesive function that the protein confers on corneodesmosomes also seems
      necessary for maintaining the architecture of the hair follicle.

PMID- 19596794
TI  - Nicotiana tabacum TTG1 contributes to ParA1-induced signalling and cell death in
      leaf trichomes.
AB  - Leaf trichomes serve as a physical barrier and can also secrete antimicrobial
      compounds to protect plants from attacks by insects and pathogens. Besides the
      use of the physical and chemical mechanisms, leaf trichomes might also support
      plant responses by communicating the extrinsic cues to plant intrinsic signalling
      pathways. Here we report a role of leaf trichomes in tobacco (Nicotiana tabacum)
      hypersensitive cell death (HCD) induced by ParA1, an elicitin protein from a
      plant-pathogenic oomycete. After localized treatment with ParA1, reactive oxygen
      species were produced first in the leaf trichomes and then in mesophylls.
      Reactive oxygen species are a group of intracellular signals that are crucial for
      HCD to develop and for cells to undergo cell death subsequent to chromatin
      condensation, a hallmark of HCD. These events were impaired when the production
      of hydrogen peroxide (H(2)O(2)) was inhibited by catalase or a NADPH-oxidase
      inhibitor applied to trichomes, suggesting the importance of H(2)O(2) in the
      pathway of HCD signal transduction from the trichomes to mesophylls. This pathway
      was no longer activated when leaf trichomes were treated with C51S, a ParA1
      mutant protein defective in its interaction with N. tabacum TTG1 (NtTTG1), which
      is a trichome protein that binds ParA1, rather than C51S, in vitro and in
      trichome cells. The ParA1-NtTTG1 interaction and the HCD pathway were also
      abrogated when NtTTG1 was silenced in the trichomes. These observations suggest
      that NtTTG1 plays an essential role in HCD signal transduction from leaf
      trichomes to mesophylls.

PMID- 19596795
TI  - FAM29A, a target of Plk1 regulation, controls the partitioning of NEDD1 between
      the mitotic spindle and the centrosomes.
AB  - We previously showed that FAM29A, a spindle-associated protein, promotes
      microtubule-dependent microtubule amplification through its interaction with and
      recruitment of NEDD1, the targeting subunit of the gamma-tubulin ring complex. We
      report here that FAM29A is regulated by Plk1, a kinase essential for spindle
      assembly and its bipolarity. Plk1, FAM29A and NEDD1 form three separate complexes
      in vivo, not one single complex. Plk1 recruits FAM29A to spindle microtubules,
      which, in turn, targets NEDD1 to the spindle. Plk1 also recruits NEDD1 to the
      centrosomes, probably through a Plk1-NEDD1 interaction, but this interaction does
      not contribute to targeting NEDD1 to the spindle. Altering intracellular levels
      of FAM29A changes the distribution of NEDD1 between the centrosomes and the
      spindle, indicating that FAM29A controls the partition of NEDD1 between these two
      mitotic structures. Thus, Plk1 promotes microtubule nucleation from the
      centrosomes through a FAM29A-independent pathway and from the spindle through a
      FAM29A-dependent pathway. FAM29A controls the relative contributions of these two
      pathways to microtubule polymerization during mitosis.

PMID- 19596796
TI  - Tssk6 is required for Izumo relocalization and gamete fusion in the mouse.
AB  - One of the most important processes in fertilization is the fusion of egg and
      sperm; however, the molecular mechanisms involved in this process are not well
      understood. So far, using genetic approaches, only two proteins have been
      demonstrated to be necessary for this process: Izumo in sperm and CD9 in the egg.
      Here we demonstrate that sperm produced by Tssk6 (Sstk)-null mice present defects
      that prevent the successful fertilization of eggs in vitro and the fusion to zona
      pellucida-free eggs. Tssk6 is a member of the testis-specific serine kinase
      family of proteins and is expressed postmeiotically in male germ cells. In order
      for fusion to occur, during the process known as acrosome reaction Izumo needs to
      relocate from the anterior head to other regions, including the postacrosomal
      compartment. Tssk6-null sperm fails to relocate Izumo during the acrosome
      reaction. Agents that interfere with actin dynamics blocked the acrosome-reaction
      associated translocation of Izumo that is required for fusion in wild-type sperm.
      Additionally, actin polymerization was compromised in Tssk6-null sperm. Taken
      together, our results indicate that Tssk6 is involved in sperm-egg fusion through
      the regulation of actin polymerization and changes in Izumo localization.

PMID- 19596798
TI  - Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor
      signaling during differentiation induction of 3T3-L1 preadipocytes.
AB  - The first stage of 3T3-L1 adipocyte differentiation is growth arrest, which is
      achieved by contact inhibition at confluence. In growth-arrested confluent 3T3-L1
      preadipocytes, alpha-tubulin acetylation and primary-cilium formation were
      induced. The blockade of primary-cilium formation by suppressing IFT88 or Kif3a
      inhibited 3T3-L1 adipocyte differentiation. IGF-1 (IGF-I)-receptor signaling,
      which is essential for differentiation induction, was sensitized by the formation
      of a primary cilium in confluent 3T3-L1 preadipocytes. The receptor located in
      primary cilium was more sensitive to insulin stimulation than that not located in
      cilia. During cilium formation, insulin receptor substrate 1 (IRS-1), one of the
      important downstream signaling molecules of the IGF-1 receptor, was recruited to
      the basal body at which it was phosphorylated on tyrosine by the receptor kinase
      in cilia. Akt-1, an important signal molecule of the IGF-1 receptor in adipocyte
      differentiation, was also activated at the basal body. These IGF-1-receptor
      signaling processes were all inhibited in IFT88- or Kif3a-knockdown cells. Thus,
      the primary cilium and its basal body formed an organized signaling pathway for
      the IGF-1 receptor to induce adipocyte differentiation in confluent 3T3-L1
      preadipocytes.

PMID- 19596797
TI  - Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM
      degradation.
AB  - Invadopodia are actin-based projections enriched with proteases, which invasive
      cancer cells use to degrade the extracellular matrix (ECM). The Phox homology
      (PX)-Src homology (SH)3 domain adaptor protein Tks5 (also known as SH3PXD2A)
      cooperates with Src tyrosine kinase to promote invadopodia formation but the
      underlying pathway is not clear. Here we show that Src phosphorylates Tks5 at
      Y557, inducing it to associate directly with the SH3-SH2 domain adaptor proteins
      Nck1 and Nck2 in invadopodia. Tks5 mutants unable to bind Nck show reduced matrix
      degradation-promoting activity and recruit actin to invadopodia inefficiently.
      Conversely, Src- and Tks5-driven matrix proteolysis and actin assembly in
      invadopodia are enhanced by Nck1 or Nck2 overexpression and inhibited by Nck1
      depletion. We show that clustering at the plasma membrane of the Tks5 inter-SH3
      region containing Y557 triggers phosphorylation at this site, facilitating Nck
      recruitment and F-actin assembly. These results identify a Src-Tks5-Nck pathway
      in ECM-degrading invadopodia that shows parallels with pathways linking several
      mammalian and pathogen-derived proteins to local actin regulation.

PMID- 19596799
TI  - FAK, PIP5KIgamma and gelsolin cooperatively mediate force-induced expression of
      alpha-smooth muscle actin.
AB  - During the development of pressure-induced cardiac hypertrophy, fibroblasts are
      activated to become myofibroblasts, which exhibit actin-cytoskeletal remodeling
      and express alpha-smooth muscle actin (SMA; encoded by ACTA2). Currently, the
      mechanosensing signaling pathways that regulate SMA expression are not defined.
      Because focal-adhesion complexes are putative mechanosensing organelles, we
      examined the role of focal adhesion kinase (FAK) and its interaction with
      gelsolin in the regulation of SMA expression. We subjected NIH3T3 cells to
      tensile forces (0.65 pN/mum(2)) by using collagen-coated magnetite beads attached
      to integrins. After stimulation by mechanical force, FAK and gelsolin were
      recruited to magnetite beads and there was increased phosphorylation of
      Tyr397FAK. Mechanical force enhanced SMA promoter activity by twofold; this
      increased activity was blocked by FAK knockdown using siRNA and by deletion of
      gelsolin. Force-induced nuclear translocation of MRTF-A, a transcriptional co
      activator of SMA that is regulated by actin filaments, was also reduced by FAK
      knockdown. Phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], which
      uncaps gelsolin from actin filaments, was enriched at sites of force application.
      Type-I phosphatidylinositol 4-phosphate 5 kinase-gamma (PIP5KIgamma), which
      generates PtdIns(4,5)P(2), associated with FAK and was required for force
      mediated SMA-promoter activity and actin assembly. Catalytically inactive
      PIP5KIgamma inhibited force-induced phosphorylation of FAK at Tyr397. These data
      suggest a novel pathway in which mechanosensing by FAK regulates actin assembly
      via gelsolin and the activity of PIP5KIgamma; actin assembly in turn controls SMA
      expression via MRTF-A.

PMID- 19596800
TI  - Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of
      the actin cytoskeleton.
AB  - Meckel-Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder
      caused by mutations in genes that encode components of the primary cilium and
      basal body. Here we show that two MKS proteins, MKS1 and meckelin, that are
      required for centrosome migration and ciliogenesis interact with actin-binding
      isoforms of nesprin-2 (nuclear envelope spectrin repeat protein 2, also known as
      Syne-2 and NUANCE). Nesprins are important scaffold proteins for maintenance of
      the actin cytoskeleton, nuclear positioning and nuclear-envelope architecture.
      However, in ciliated-cell models, meckelin and nesprin-2 isoforms colocalized at
      filopodia prior to the establishment of cell polarity and ciliogenesis. Loss of
      nesprin-2 and nesprin-1 shows that both mediate centrosome migration and are then
      essential for ciliogenesis, but do not otherwise affect apical-basal polarity.
      Loss of meckelin (by siRNA and in a patient cell-line) caused a dramatic
      remodelling of the actin cytoskeleton, aberrant localization of nesprin-2
      isoforms to actin stress-fibres and activation of RhoA signalling. These findings
      further highlight the important roles of the nesprins during cellular and
      developmental processes, particularly in general organelle positioning, and
      suggest that a mechanistic link between centrosome positioning, cell polarity and
      the actin cytoskeleton is required for centrosomal migration and is essential for
      early ciliogenesis.

PMID- 19596803
TI  - IL-9 as a mediator of Th17-driven inflammatory disease.
AB  - We report that like other T cells cultured in the presence of transforming growth
      factor (TGF) beta, Th17 cells also produce interleukin (IL) 9. Th17 cells
      generated in vitro with IL-6 and TGF-beta as well as purified ex vivo Th17 cells
      both produced IL-9. To determine if IL-9 has functional consequences in Th17
      mediated inflammatory disease, we evaluated the role of IL-9 in the development
      and progression of experimental autoimmune encephalomyelitis, a mouse model of
      multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor
      deficiency attenuates disease, and this correlates with decreases in Th17 cells
      and IL-6-producing macrophages in the central nervous system, as well as mast
      cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9
      as a Th17-derived cytokine that can contribute to inflammatory disease.

PMID- 19596804
TI  - Group B Streptococcus suppression of phagocyte functions by protein-mediated
      engagement of human Siglec-5.
AB  - Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections
      in human newborns. A key GBS virulence factor is its capsular polysaccharide
      (CPS), displaying terminal sialic acid (Sia) residues which block deposition and
      activation of complement on the bacterial surface. We recently demonstrated that
      GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig)
      superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed
      on the surface of leukocytes. We report the unexpected discovery that certain GBS
      strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via
      the cell wall-anchored beta protein, resulting in recruitment of SHP protein
      tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with
      Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS beta
      protein binding to Siglec-5 functions to impair human leukocyte phagocytosis,
      oxidative burst, and extracellular trap production, promoting bacterial survival.
      We conclude that protein-mediated functional engagement of an inhibitory host
      lectin receptor promotes bacterial innate immune evasion.

PMID- 19596805
TI  - S region sequence, RNA polymerase II, and histone modifications create chromatin
      accessibility during class switch recombination.
AB  - Immunoglobulin class switch recombination is governed by long-range interactions
      between enhancers and germline transcript promoters to activate transcription and
      modulate chromatin accessibility to activation-induced cytidine deaminase (AID).
      However, mechanisms leading to the differential targeting of AID to switch (S)
      regions but not to constant (C(H)) regions remain unclear. We show that S and
      C(H) regions are dynamically modified with histone marks that are associated with
      active and repressed chromatin states, respectively. Chromatin accessibility is
      superimposable with the activating histone modifications, which extend throughout
      S regions irrespective of length. High density elongating RNA polymerase II (RNAP
      II) is detected in S regions, suggesting that the transcription machinery has
      paused and stalling is abolished by deletion of the S region. We propose that
      RNAP II enrichment facilitates recruitment of histone modifiers to generate
      accessibility. Thus, the histone methylation pattern produced by transcription
      localizes accessible chromatin to S regions, thereby focusing AID attack.

PMID- 19596806
TI  - Cooperative regulation of Ca(v)1.2 channels by intracellular Mg(2+), the proximal
      C-terminal EF-hand, and the distal C-terminal domain.
AB  - L-type Ca(2+) currents conducted by Ca(v)1.2 channels initiate excitation
      contraction coupling in cardiac myocytes. Intracellular Mg(2+) (Mg(i)) inhibits
      the ionic current of Ca(v)1.2 channels. Because Mg(i) is altered in ischemia and
      heart failure, its regulation of Ca(v)1.2 channels is important in understanding
      cardiac pathophysiology. Here, we studied the effects of Mg(i) on voltage
      dependent inactivation (VDI) of Ca(v)1.2 channels using Na(+) as permeant ion to
      eliminate the effects of permeant divalent cations that engage the Ca(2+)
      dependent inactivation process. We confirmed that increased Mg(i) reduces peak
      ionic currents and increases VDI of Ca(v)1.2 channels in ventricular myocytes and
      in transfected cells when measured with Na(+) as permeant ion. The increased rate
      and extent of VDI caused by increased Mg(i) were substantially reduced by
      mutations of a cation-binding residue in the proximal C-terminal EF-hand,
      consistent with the conclusion that both reduction of peak currents and
      enhancement of VDI result from the binding of Mg(i) to the EF-hand (K(D)
      approximately 0.9 mM) near the resting level of Mg(i) in ventricular myocytes.
      VDI was more rapid for L-type Ca(2+) currents in ventricular myocytes than for
      Ca(v)1.2 channels in transfected cells. Coexpression of Ca(v)beta(2b) subunits
      and formation of an autoinhibitory complex of truncated Ca(v)1.2 channels with
      noncovalently bound distal C-terminal domain (DCT) both increased VDI in
      transfected cells, indicating that the subunit structure of the Ca(v)1.2 channel
      greatly influences its VDI. The effects of noncovalently bound DCT on peak
      current amplitude and VDI required Mg(i) binding to the proximal C-terminal EF
      hand and were prevented by mutations of a key divalent cation-binding amino acid
      residue. Our results demonstrate cooperative regulation of peak current amplitude
      and VDI of Ca(v)1.2 channels by Mg(i), the proximal C-terminal EF-hand, and the
      DCT, and suggest that conformational changes that regulate VDI are propagated
      from the DCT through the proximal C-terminal EF-hand to the channel-gating
      mechanism.

PMID- 19596807
TI  - A translational signature for nucleosome positioning in vivo.
AB  - In vivo nucleosomes often occupy well-defined preferred positions on genomic DNA.
      An important question is to what extent these preferred positions are directly
      encoded by the DNA sequence itself. We derive here from in vivo positions,
      accurately mapped by partial micrococcal nuclease digestion, a translational
      positioning signal that identifies the approximate midpoint of DNA bound by a
      histone octamer. This midpoint is, on average, highly A/T rich ( approximately
      73%) and, in particular, the dinucleotide TpA occurs preferentially at this and
      other outward-facing minor grooves. We conclude that in this set of sequences the
      sequence code for DNA bending and nucleosome positioning differs from the other
      described sets and we suggest that the enrichment of AT-containing dinucleotides
      at the centre is required for local untwisting. We show that this signature is
      preferentially associated with nucleosomes flanking promoter regions and suggest
      that it contributes to the establishment of gene-specific nucleosome arrays.

PMID- 19596808
TI  - Integrase-directed recovery of functional genes from genomic libraries.
AB  - Large population sizes, rapid growth and 3.8 billion years of evolution firmly
      establish microorganisms as a major source of the planet's biological and genetic
      diversity. However, up to 99% of the microorganisms in a given environment cannot
      be cultured. Culture-independent methods that directly access the genetic
      potential of an environmental sample can unveil new proteins with diverse
      functions, but the sequencing of random DNA can generate enormous amounts of
      extraneous data. Integrons are recombination systems that accumulate open reading
      frames (gene cassettes), many of which code for functional proteins with enormous
      adaptive potential. Some integrons harbor hundreds of gene cassettes and evidence
      suggests that the gene cassette pool may be limitless in size. Accessing this
      genetic pool has been hampered since sequence-based techniques, such as
      hybridization or PCR, often recover only partial genes or a small subset of those
      present in the sample. Here, a three-plasmid genetic strategy for the sequence
      independent recovery of gene cassettes from genomic libraries is described and
      its use by retrieving functional gene cassettes from the chromosomal integron of
      Vibrio vulnificus ATCC 27562 is demonstrated. By manipulating the natural
      activity of integrons, we can gain access to the caches of functional genes
      amassed by these structures.

PMID- 19596809
TI  - The role of deadenylation in the degradation of unstable mRNAs in trypanosomes.
AB  - Removal of the poly(A) tail is the first step in the degradation of many
      eukaryotic mRNAs. In metazoans and yeast, the Ccr4/Caf1/Not complex has the
      predominant deadenylase activity, while the Pan2/Pan3 complex may trim poly(A)
      tails to the correct size, or initiate deadenylation. In trypanosomes, turnover
      of several constitutively-expressed or long-lived mRNAs is not affected by
      depletion of the 5'-3' exoribonuclease XRNA, but is almost completely inhibited
      by depletion of the deadenylase CAF1. In contrast, two highly unstable mRNAs,
      encoding EP procyclin and a phosphoglycerate kinase, PGKB, accumulate when XRNA
      levels are reduced. We here show that degradation of EP mRNA was partially
      inhibited after CAF1 depletion. RNAi-targeting trypanosome PAN2 had a mild effect
      on global deadenylation, and on degradation of a few mRNAs including EP. By
      amplifying and sequencing degradation intermediates, we demonstrated that a
      reduction in XRNA had no effect on degradation of a stable mRNA encoding a
      ribosomal protein, but caused accumulation of EP mRNA fragments that had lost
      substantial portions of the 5' and 3' ends. The results support a model in which
      trypanosome mRNAs can be degraded by at least two different, partially
      independent, cytoplasmic degradation pathways attacking both ends of the mRNA.

PMID- 19596810
TI  - Differences between Ca2+ and Mg2+ in DNA binding and release by the SfiI
      restriction endonuclease: implications for DNA looping.
AB  - Many enzymes acting on DNA require Mg(2+) ions not only for catalysis but also to
      bind DNA. Binding studies often employ Ca(2+) as a substitute for Mg(2+), to
      promote DNA binding whilst disallowing catalysis. The SfiI endonuclease requires
      divalent metal ions to bind DNA but, in contrast to many systems where Ca(2+)
      mimics Mg(2+), Ca(2+) causes SfiI to bind DNA almost irreversibly. Equilibrium
      binding by wild-type SfiI cannot be conducted with Mg(2+) present as the DNA is
      cleaved so, to study the effect of Mg(2+) on DNA binding, two catalytically
      inactive mutants were constructed. The mutants bound DNA in the presence of
      either Ca(2+) or Mg(2+) but, unlike wild-type SfiI with Ca(2+), the binding was
      reversible. With both mutants, dissociation was slow with Ca(2+) but was in one
      case much faster with Mg(2+). Hence, Ca(2+) can affect DNA binding differently
      from Mg(2+). Moreover, SfiI is an archetypal system for DNA looping; on DNA with
      two recognition sites, it binds to both sites and loops out the intervening DNA.
      While the dynamics of looping cannot be measured with wild-type SfiI and Ca(2+),
      it becomes accessible with the mutant and Mg(2+).

PMID- 19596811
TI  - Stabilization of quadruplex DNA perturbs telomere replication leading to the
      activation of an ATR-dependent ATM signaling pathway.
AB  - Functional telomeres are required to maintain the replicative ability of cancer
      cells and represent putative targets for G-quadruplex (G4) ligands. Here, we show
      that the pentacyclic acridinium salt RHPS4, one of the most effective and
      selective G4 ligands, triggers damages in cells traversing S phase by interfering
      with telomere replication. Indeed, we found that RHPS4 markedly reduced BrdU
      incorporation at telomeres and altered the dynamic association of the telomeric
      proteins TRF1, TRF2 and POT1, leading to chromosome aberrations such as telomere
      fusions and telomere doublets. Analysis of the molecular damage pathway revealed
      that RHPS4 induced an ATR-dependent ATM signaling that plays a functional role in
      the cellular response to RHPS4 treatment. We propose that RHPS4, by stabilizing
      G4 DNA at telomeres, impairs fork progression and/or telomere processing
      resulting in telomere dysfunction and activation of a replication stress response
      pathway. The detailed understanding of the molecular mode of action of this class
      of compounds makes them attractive tools to understand telomere biology and
      provides the basis for a rational use of G4 ligands for the therapy of cancer.

PMID- 19596812
TI  - Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T
      segment navigation.
AB  - DNA gyrase is an indispensible marvelous molecular machine in manipulating the
      DNA topology for the prokaryotes. In the 'two-gate' mechanism of DNA
      topoisomerase, T-segment navigation from N- to DNA-gate is a critical step, but
      the structural basis supporting this scheme is unclear. The crystal structure of
      DNA gyrase B' subfragment from Mycobacterium tuberculosis reveals an intrinsic
      homodimer. The two subunits, each consisting of a Tail and a Toprim domain, are
      tightly packed one another to form a 'crab-like' organization never observed
      previously from yeast topo II. Structural comparisons show two orientational
      alterations of the Tail domain, which may be dominated by a 43-residue peptide at
      the B' module C-terminus. A highly conserved pentapeptide mediates large-scale
      intrasubunit conformational change as a hinge point. Mutational studies highlight
      the significant roles of a negatively charge cluster on a groove at dimer
      interface. On the basis of structural analysis and mutation experiments, a sluice
      like model for T-segment transport is proposed.

PMID- 19596813
TI  - LSM1 over-expression in Saccharomyces cerevisiae depletes U6 snRNA levels.
AB  - Lsm1 is a component of the Lsm1-7 complex involved in cytoplasmic mRNA
      degradation. Lsm1 is over-expressed in multiple tumor types, including over 80%
      of pancreatic tumors, and increased levels of Lsm1 protein have been shown to
      induce carcinogenic effects. Therefore, understanding the perturbations in cell
      process due to increased Lsm1 protein may help to identify possible therapeutics
      targeting tumors over-expressing Lsm1. Herein, we show that LSM1 over-expression
      in the yeast Saccharomyces cerevisiae inhibits growth primarily due to U6 snRNA
      depletion, thereby altering pre-mRNA splicing. The decrease in U6 snRNA levels
      causes yeast strains over-expressing Lsm1 to be hypersensitive to loss of other
      proteins required for production or function of the U6 snRNA, supporting a model
      wherein excess Lsm1 reduces the availability of the Lsm2-7 proteins, which also
      assemble with Lsm8 to form a complex that binds and stabilizes the U6 snRNA.
      Yeast strains over-expressing Lsm1 also display minor alterations in mRNA decay
      and demonstrate increased susceptibility to mutations inhibiting cytoplasmic
      deadenylation, a process required for both 5'-to-3' and 3'-to-5' pathways of
      exonucleolytic decay. These results suggest that inhibition of splicing and/or
      deadenylation may be effective therapies for Lsm1-over-expressing tumors.

PMID- 19596815
TI  - Conserved functional domains and a novel tertiary interaction near the pseudoknot
      drive translational activity of hepatitis C virus and hepatitis C virus-like
      internal ribosome entry sites.
AB  - The translational activity of the hepatitis C virus (HCV) internal ribosome entry
      site (IRES) and other HCV-like IRES RNAs depends on structured RNA elements in
      domains II and III, which serve to recruit the ribosomal 40S subunit, eukaryotic
      initiation factor (eIF) 3 and the ternary eIF2/Met-tRNA(i)(Met)/GTP complex and
      subsequently domain II assists subunit joining. Porcine teschovirus-1 talfan (PTV
      1) is a member of the Picornaviridae family, with a predicted HCV-like secondary
      structure, but only stem-loops IIId and IIIe in the 40S-binding domain display
      significant sequence conservation with the HCV IRES. Here, we use chemical
      probing to show that interaction sites with the 40S subunit and eIF3 are
      conserved between HCV and HCV-like IRESs. In addition, we reveal the functional
      role of a strictly conserved co-variation between a purine-purine mismatch near
      the pseudoknot (A-A/G) and the loop sequence of domain IIIe (GAU/CA). These
      nucleotides are involved in a tertiary interaction, which serves to stabilize the
      pseudoknot structure and correlates with translational efficiency in both the PTV
      1 and HCV IRES. Our data demonstrate conservation of functional domains in HCV
      and HCV-like IRESs including a more complex structure surrounding the pseudoknot
      than previously assumed.

PMID- 19596814
TI  - Silencing of microRNA-155 in mice during acute inflammatory response leads to
      derepression of c/ebp Beta and down-regulation of G-CSF.
AB  - microRNA-155 (miR-155) has been implicated as a central regulator of the immune
      system, but its function during acute inflammatory responses is still poorly
      understood. Here we show that exposure of cultured macrophages and mice to
      lipopolysaccharide (LPS) leads to up-regulation of miR-155 and that the
      transcription factor c/ebp Beta is a direct target of miR-155. Interestingly,
      expression profiling of LPS-stimulated macrophages combined with overexpression
      and silencing of miR-155 in murine macrophages and human monocytic cells
      uncovered marked changes in the expression of granulocyte colony-stimulating
      factor (G-CSF), a central regulator of granulopoiesis during inflammatory
      responses. Consistent with these data, we show that silencing of miR-155 in LPS
      treated mice by systemically administered LNA-antimiR results in derepression of
      the c/ebp Beta isoforms and down-regulation of G-CSF expression in mouse
      splenocytes. Finally, we report for the first time on miR-155 silencing in vivo
      in a mouse inflammation model, which underscores the potential of miR-155
      antagonists in the development of novel therapeutics for treatment of chronic
      inflammatory diseases.

PMID- 19596816
TI  - Improvement of RNA secondary structure prediction using RNase H cleavage and
      randomized oligonucleotides.
AB  - RNA secondary structure prediction using free energy minimization is one method
      to gain an approximation of structure. Constraints generated by enzymatic mapping
      or chemical modification can improve the accuracy of secondary structure
      prediction. We report a facile method that identifies single-stranded regions in
      RNA using short, randomized DNA oligonucleotides and RNase H cleavage. These
      regions are then used as constraints in secondary structure prediction. This
      method was used to improve the secondary structure prediction of Escherichia coli
      5S rRNA. The lowest free energy structure without constraints has only 27% of the
      base pairs present in the phylogenetic structure. The addition of constraints
      from RNase H cleavage improves the prediction to 100% of base pairs. The same
      method was used to generate secondary structure constraints for yeast tRNA(Phe),
      which is accurately predicted in the absence of constraints (95%). Although RNase
      H mapping does not improve secondary structure prediction, it does eliminate all
      other suboptimal structures predicted within 10% of the lowest free energy
      structure. The method is advantageous over other single-stranded nucleases since
      RNase H is functional in physiological conditions. Moreover, it can be used for
      any RNA to identify accessible binding sites for oligonucleotides or small
      molecules.

PMID- 19596821
TI  - Altering and assessing persistence of genetically modified E. coli MG1655 in the
      large bowel.
AB  - One of the primary factors limiting the efficacy of probiotic therapies is short
      persistence time. Utilizing a novel method for assessment of persistence in the
      large bowel independent of survival of the organisms in the upper GI tract, we
      tested whether overexpression of the type 1 pilus, a colonization factor, or the
      presence of secretory immunoglobulin A (sIgA) might increase the persistence time
      of a laboratory strain of E. coli in the gut. For this purpose, cecal ostomies
      were created in mice and bacteria were placed in the ostomies, with or without
      sIgA. The persistence of the bacteria was assessed by evaluating the length of
      time after placement in which the bacteria were found in fecal samples. E. coli
      MG1655 expressing pili with the mannose-specific adhesin persisted in vivo
      significantly longer [mean (hours) +/- SEM: 91.50 +/- 15.98, n = 12] than
      bacteria expressing pili without adhesin [43.67 +/- 8.22, n = 12] (P = 0.01) and
      significantly longer than bacteria expressing neither pili nor adhesin [22.00 +/-
      4.22, n = 12] (P = 0.0004). Although the persistence time of bacteria was not
      significantly affected by the presence of sIgA, the sIgA did cause a relative
      increase in retention of inert particles. These results, combined with an acute
      increase in stool production and stool water content in those animals not
      receiving sIgA following introduction of bacteria, suggest that sIgA might have
      anti-inflammatory properties in the gut when administered with enteric bacteria.
      Modifying expression of probiotic colonization factors may provide substantial
      benefit to patients with digestive tract diseases by virtue of increased
      persistence of the probiotic and, in the case of sIgA, an anti-inflammatory
      effect. This novel in vivo model may be useful in evaluating persistence time in
      a variety of current and future probiotic regimens.

PMID- 19596820
TI  - Engineering nanomaterial surfaces for biomedical applications.
AB  - Nanomaterials, possessing unique physical and chemical properties, have attracted
      much interest and generated wide varieties of applications. Recent investigations
      of functionalized nanomaterials have expanded into the biological area, providing
      a versatile platform in biomedical applications such as biomolecular sensing,
      biological imaging, drug delivery and disease therapy. Bio-functions and bio
      compatibility of nanomaterials are realized by introducing synthetic ligands or
      natural biomolecules onto nanomaterials, and combining ligand-receptor biological
      interactions with intrinsic nanomaterial properties. Common strategies of
      engineering nanomaterial surfaces involve physisorption or chemisorption of
      desired ligands. We developed a photochemically initiated surface coupling
      chemistry, bringing versatility and simplicity to nanomaterial functionalization.
      The method was applied to attach underivatized carbohydrates efficiently on gold
      and iron oxide nanoparticles, and the resulting glyconanoparticles were
      successfully used as a sensitive biosensing system probing specific interactions
      between carbohydrates and proteins as well as bacteria.

PMID- 19596822
TI  - Current perspectives on Akt Akt-ivation and Akt-ions.
AB  - The serine/threonine kinase Akt is an effector of PI3K-generated
      phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and is a principle
      mediator of growth factor-induced signal transduction. Akt is activated through
      phosphorylation by specific kinases, and its activity is reduced directly by
      phosphorylation-site-specific phosphatases. In addition, Akt activity is
      effectively reduced by the action of phosphatases which dephosphorylate
      PI(3,4,5)P3, thereby reducing the levels of the essential lipid activators of
      PDK1 and Akt. The functions of Akt are pleiotropic and include regulation of
      cellular proliferation, differentiation, protein synthesis, and survival. Akt
      stimulates protein synthesis through actions on mTOR/p70S6K, and promotes
      survival by phosphorylating and inactivating pro-apoptotic molecules such as
      Ask1, Bad, Bax, and FoxO3a. Furthermore, loss of Akt decreases the intracellular
      ATP:AMP ratio, thus establishing a role for Akt in energy regulation. Three
      isoforms of Akt have been identified, and although redundant functions between
      isoforms exist, recent investigations have enumerated unique functions for each.
      Therefore, targeting specific Akt isozymes in a tissue- and context-specific
      fashion may lead to a greater understanding of Akt-mediated processes.

PMID- 19596824
TI  - Comparison of isoflurane-, sevoflurane-, and desflurane-induced pre- and
      postconditioning against myocardial infarction in mice in vivo.
AB  - The murine in vivo model of acute myocardial infarction is increasingly used to
      investigate anesthetic-induced preconditioning (APC) and postconditioning
      (APOST). However, in mice the potency of different volatile anesthetics to reduce
      myocardial infarct size (IS) has never been investigated systematically nor in a
      head to head comparison with regard to ischemic preconditioning (IPC) and
      postconditioning (IPOST). Male C57BL/6 mice were subjected to 45 min of coronary
      artery occlusion (CAO) and 180 min of reperfusion. To induce APC, 1.0 MAC
      isoflurane (ISO), sevoflurane (SEVO) or desflurane (DES) was administered 30 min
      prior to CAO for 15 min. In an additional group, ISO was administered 45 min
      prior to CAO for 30 min. To induce APOST, 1.0 MAC ISO, SEVO or DES was
      administered for 18 min starting 3 min prior to the end of CAO. IPC was induced
      by 3 or 6 cycles of 5 min ischemia/reperfusion, 40 or 60 min prior to CAO,
      respectively. IPOST was induced by 3 cycles of 30 sec reperfusion/ischemia at the
      beginning of reperfusion. Area at risk (AAR) and IS were determined with Evans
      Blue and TTC staining, respectively. IS (IS/AAR) was 50 +/- 4% (mean +/- SEM) in
      the control group and was significantly (*P < 0.05) reduced by 3x5 IPC (26 +/-
      3%*), 6 x 5 IPC (26 +/- 4%*), IPOST (20 +/- 2%*), ISO APOST (19 +/- 1%*), SEVO
      APOST (15 +/- 1%*), DES APOST (14 +/- 2%*) and SEVO APC (27 +/- 6%*). ISO APC
      significantly reduced IS compared to control when administered 30 min (33 +/-
      4%*), but not when administered 15 min (48 +/- 6%). DES APC significantly reduced
      IS compared to control and to SEVO APC (7 +/- 1%*). Within the paradigm of
      preconditioning, the potency of volatile anesthetics to reduce myocardial infarct
      size in mice significantly increases from ISO over SEVO to DES, whereas within
      the paradigm of postconditioning the potency of these volatile anesthetics to
      reduce myocardial infarct size in mice is similar.

PMID- 19596825
TI  - Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in
      rats.
AB  - Protective effect of hydrogen (H(2)) gas on cardiac ischemia-reperfusion (I/R)
      injury has been demonstrated previously. This study was designed to test the
      hypothesis that hydrogen-rich saline (saline saturated with molecular hydrogen),
      which is easy to use, induces cardioprotection against ischemia (30 min) and
      reperfusion (24 h) injury in rats. Adult male Sprague-Dawley rats underwent 30
      min occlusion of the left anterior descending (LAD) coronary artery and 24-h
      reperfusion. Intraperitoneal injection of hydrogen-rich saline before reperfusion
      significantly decreased plasma and myocardium malondialdehyde (MDA)
      concentration, decreased cardiac cell apoptosis, and myocardial 8
      hydroxydeoxyguanosine (8-OHdG) in area at risk zones (AAR), suppressed the
      activity of caspase-3, and reduced infarct size. The heart function parameters
      including left ventricular systolic pressure (LVSP), left ventricular diastolic
      pressure (LVDP), +(dP/dt)(max) and -(dP/dt)(max) were also significantly improved
      24 h after reperfusion. It is concluded that hydrogen-rich saline is a novel,
      simple, safe, and effective method to attenuate myocardial I/R injury.

PMID- 19596823
TI  - Immature copper-zinc superoxide dismutase and familial amyotrophic lateral
      sclerosis.
AB  - Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited
      form of amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease, motor neuron
      disease). Insoluble forms of mutant SOD1 accumulate in neural tissues of human
      ALS patients and in spinal cords of transgenic mice expressing these
      polypeptides, suggesting that SOD1-linked ALS is a protein misfolding disorder.
      Understanding the molecular basis for how the pathogenic mutations give rise to
      SOD1 folding intermediates, which may themselves be toxic, is therefore of keen
      interest. A critical step on the SOD1 folding pathway occurs when the copper
      chaperone for SOD1 (CCS) modifies the nascent SOD1 polypeptide by inserting the
      catalytic copper cofactor and oxidizing its intrasubunit disulfide bond. Recent
      studies reveal that pathogenic SOD1 proteins coming from cultured cells and from
      the spinal cords of transgenic mice tend to be metal-deficient and/or lacking the
      disulfide bond, raising the possibility that the disease-causing mutations may
      enhance levels of SOD1-folding intermediates by preventing or hindering CCS
      mediated SOD1 maturation. This mini-review explores this hypothesis by
      highlighting the structural and biophysical properties of the pathogenic SOD1
      mutants in the context of what is currently known about CCS structure and action.
      Other hypotheses as to the nature of toxicity inherent in pathogenic SOD1
      proteins are not covered.

PMID- 19596826
TI  - Generation of expression clone set for functional proteomics of human gastric and
      liver cancers.
AB  - Two thousand sixty-eight multi-purpose expression clones for the 326 candidate
      genes related to gastric or liver cancers were constructed using the Gateway
      system. These clones can be expressed as His, Glutathione-S-transferase (GST) or
      Enhanced version of the green fluorescent protein (EGFP) fusion proteins in E.
      coli, insect cells or mammalian cells. For the 246 E. coli expression clones, the
      GST fusion proteins had greater expression efficiency and solubility than the His
      fusion proteins. Approximately 20% of the expressed proteins had unexpected
      molecular weights. A detailed sequence analysis of these clones revealed
      frameshift mutations resulting from insertion, deletion or substitution of
      nucleotides. The results indicate that these changes in the candidate genes may
      affect the occurrence of gastric or liver cancers. In addition, when 105
      proteins, which were expressed in E. coli at very low or undetectable levels,
      were expressed in insect cells, 76% of the proteins were expressed very well and
      most were soluble. We also found that most of the 30 proteins prepared using EGFP
      mammalian expression clones were localized to cellular compartments expected by
      Gene ontology (GO) and this localization was unaffected if the EGFP-fusion was at
      the N-terminal or C-terminal region of the protein. Antibody production and
      subcellular localization analysis of the candidate genes as well as a screen of
      genes involved in carcinogenesis pathways are currently in progress using these
      expression clones. These studies provide a valuable resource for developing a
      better understanding of the molecular mechanism of carcinogenesis in both gastric
      and liver cancer and would be very helpful in diagnosis and therapeutic
      predictions.

PMID- 19596827
TI  - Blockade of connexin 43 hemichannels reduces neointima formation after vascular
      injury by inhibiting proliferation and phenotypic modulation of smooth muscle
      cells.
AB  - Connexins 43 (Cx43) plays a key role in neointimal formation after vascular
      injury, but the mechanism still needs to be further explored. We hypothesized
      that the gap junction-dependent function of Cx43 to mediate intercellular
      communication has a crucial role in the development and progression of vascular
      diseases. The effect of intercellular communication mediated by Cx43 hemichannels
      on neointimal formation after vascular injury was investigated. Cx43 was
      overexpressed or knockdown in rat vascular smooth muscle cell (SMC) by
      transfection pcDNA-Cx43 plasmid or small interfering RNA (siRNA) against Cx43
      (siCx43). SMC proliferation and marker genes expression after Cx43 alteration and
      blockade of the Cx43 hemichannel were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,
      5-diphenyltetrazolium bromide assay and RT-PCR. The effect of carbenoxolone on
      neointimal formation was investigated in carotid artery injured rat model. We
      demonstrated that overexpression of Cx43 promoted SMC proliferation, meanwhile,
      mRNA expression level of smooth muscle alpha-actin and calponin, which were
      important markers of SMC in a contractile state, were down-regulated in smooth
      muscle. Knockdown of Cx43 inhibited SMC proliferation but increased SMC marker
      genes expression level. Carbenoxolone (50 muM) improved SMC contractile
      differentiation and inhibited its proliferation. Our data showed that
      carbenoxolone reduced neointimal formation after carotid artery injury. In
      summary, blockade of intercellular communication via Cx43 hemichannels reduces
      neointimal formation after vascular injury by inhibiting proliferation and
      phenotypic modulation of SMCs.

PMID- 19596828
TI  - Cell cycle arrest induced by hydrogen peroxide is associated with modulation of
      oxidative stress related genes in breast cancer cells.
AB  - Depending on the amounts present, reactive oxygen species can exert either
      beneficial or deleterious effect to cells. In the present study, we observed a
      decrease in cell viability concomitant with an increase of malondialdehyde
      concentration in hydrogen peroxide (H(2)O(2))-treated MCF-7 breast cancer cells.
      There was also a concurrent G1/S phase cell cycle arrest with increased apoptosis
      in H(2)O(2)-treated cells. Analysis of 84 oxidative stress related genes showed
      that five genes were significantly and differentially regulated, namely,
      Cytoglobin (CYGB), Forkhead box M1 (FOXM1), NADPH oxidase (NOX5), Nudix
      (nucleoside diphosphate linked moiety X)-type motif 1 (NUDT1) and Selenoprotein
      P1 (SEPP1) genes with H(2)O(2) treatment. It would seem that oxidative stress
      induces cell cycle arrest in the breast cancer by modulation of these genes.
      Manipulation of these genes, in particular FOXM1, a proliferation-specific gene
      associated with human malignancies, could stifle cancer progression and enhance
      the therapeutic efficacy of drugs which exert their effects by oxidative stress.

PMID- 19596829
TI  - Endothelin-converting enzyme inhibition in the rat model of acute heart failure:
      heart function and neurohormonal activation.
AB  - Endothelin-1 (ET-1) has been implicated in many cardiovascular diseases,
      including acute heart failure (AHF) due to myocardial ischemia. Previously we
      described the oral endothelin-converting enzyme (ECE) inhibitor, PP36, and in
      this study, we investigated its cardioprotective effect in more detail, and
      examined the role of PP36 in the neurohormonal activation in rats that had been
      subjected to acute myocardial ischemia due to the microsphere embolization of
      coronary microcirculation. PP36 treatment (3.5 x 10(-5) M/kg/day) led to a
      significant fourfold decrease in hypertensive response when big-ET-1 was
      administered to healthy, conscious rats. ECE inhibition did not affect mortality
      during the first 48 hours after ischemia initiation. Systemic hemodynamic, heart
      function, and neurohormonal activation were analyzed in the healthy control
      group, the AHF group, and the AHF+PP36 group two days after AHF induction. In
      conscious rats in the AHF+PP36 group, mean arterial pressure (MAP) was restored
      and became similar to that of the MAP of the control group. In anesthetized rats,
      in the AHF+PP36 group, MAP was not restored and was 22% lower than the MAP of the
      control group. Myocardial contractility was partially restored and cardiac
      relaxation significantly improved after PP36 application. Further analysis of
      cardiac output and peripheral resistance in anesthetized rats revealed no
      differences between the AHF group and the AHF+PP36 group. There were no
      differences in plasma ET-1 concentration, serum angiotensin converting enzyme
      activity, and in the adrenal glands' catecholamine content between the AHF group
      and the AHF+PP36 group. However, rats in the AHF+PP36 group demonstrated a 60%
      decrease in cardiac endothelial nitric oxide synthase (eNOS) protein expression,
      and a 56% reduction of myocardial norepinephrine release, when compared with the
      AHF group's animals. These results suggest that PP36 can preserve heart function
      during the recovery from acute ischemic injury, and may modulate the cardiac
      norepinephrine release and eNOS protein level.

PMID- 19596830
TI  - Effects of tumor necrosis factor-alpha and nitric oxide on prostaglandins
      secretion by the bovine oviduct differ in the isthmus and ampulla and depend on
      the phase of the estrous cycle.
AB  - To determine the possible roles of tumor necrosis factor-alpha (TNFalpha) and
      nitric oxide (NO) in the bovine oviduct, ampulla and isthmus collected during the
      estrous cycle were exposed for 18 h to TNFalpha, NO donor (NONOate), NO synthase
      inhibitors (L-NOARG, L-NAME and AMT) and oxytocin (OT) as a positive control.
      Prostaglandins (PGs) and NO(2)/NO(3) in conditioned media were measured. TNFalpha
      stimulated PGF(2alpha) secretion on Day 0 (onset of estrus = Day 0) and Days 2-3,
      in both the ampulla and isthmus, but on Days 18-20 only in ampulla. TNFalpha
      increased PGE(2) secretion in both fragments in each phase. NONOate did not
      affect PGF(2alpha) secretion on Days 18-20, whereas this NO donor stimulated
      PGF(2alpha) secretion in both fragments on Day 0 and Days 2-3. TNFalpha increased
      NO(2)/NO(3) production in every examined phase in the ampulla and on Days 2-3 in
      the isthmus. L-NAME lowered NO(2)/NO(3) production regardless of phase or
      fragment. L-NOARG and AMT lowered NO(2)/NO(3) production in both fragments on Day
      0 and Days 2-3. The possible role of TNFalpha, NO or PGs on the oviductal
      contractility during the early-luteal phase was also examined. Neither TNFalpha
      nor NONOate influenced contractility in either fragment. Although PGF(2alpha)
      stimulated the contraction in both fragments, PGE(2) decreased it. When taken
      together, TNFalpha seems to play some role as a modulator of PGF(2alpha) and
      PGE(2) production and for transferring the embryo from the oviduct to the uterus
      by stimulating NO production in the bovine oviduct.

PMID- 19596831
TI  - Enterovirus 71 infection of human dendritic cells.
AB  - Enterovirus 71 (EV71) causes death and long-term neurologic sequelae in hundreds
      of thousands of young children, but its pathogenesis remains elusive. Dendritic
      cells (DCs) play a crucial role in antiviral immunity by functioning as
      professional antigen-presenting cells to prime T cells and by secreting cytokines
      to modulate immune responses. Here, we show that EV71 productively infected human
      immature DCs and expressed viral antigen in DCs. EV71 entry into DCs was
      partially mediated by DC-SIGN. Further analyses revealed that EV71 increased the
      viability, activation, release of cytokines, interleukin-6, interleukin-12, and
      tumor necrosis factor-alpha in DCs. Moreover, EV71 enabled DCs to stimulate T
      cell proliferation. Collectively, these findings suggest that EV71 infection of
      human DCs in vivo is very likely to elicit protective immunity, because in
      infected mice, both T cells and IL-6 function to reduce mortality.

PMID- 19596832
TI  - Liver cyst cytokines promote endothelial cell proliferation and development.
AB  - Autosomal dominant polycystic kidney (ADPKD) is highly prevalent genetic disease.
      Liver cyst disease is the most common extrarenal manifestation in ADPKD and
      accounts for up to 10% of ADPKD morbidity and mortality. The clinical features of
      ADPKD liver disease arise from dramatic increases in liver cyst volumes. To
      identify mechanisms that promote liver cyst growth, the present study
      characterized the degree of vascularization of liver cyst walls and determined
      that cyst-specific cytokines and growth factors can drive endothelial cell
      proliferation and development. Microscopic techniques demonstrated liver cyst
      walls are well vascularized. A comparative analysis found the vascular density in
      free liver cyst walls was greater in mice than in humans. Treatment of human
      micro-vascular endothelial cells (HMEC-1) with human liver cyst fluid (huLCF)
      induced a rapid increase in vascular endothelium growth factor receptor 2
      (VEGFR2) phosphorylation that persisted for 45-60 min and was blocked by 20
      microM SU5416, a VEGFR tyrosine kinase inhibitor. Similarly, huLCF treatment of
      HMEC-1 cells induced an increase in the cell proliferation rate (131 +/- 6% of
      control levels; P > 0.05) and the degree of vascular development ('tube' diameter
      assay: 92 +/- 14 microm for huLCF vs. 12 +/- 7 microm for vehicle); P > 0.05).
      Both cell proliferation and vascular development were sensitive to SU5416. These
      studies indicate that factors secreted by liver cyst epithelia can activate VEGF
      signaling pathways and induce endothelial cell proliferation and differentiation.
      The present studies suggest that targeting VEGFR2-dependent angiogenesis may be
      an effective therapeutic strategy in blocking ADPKD liver cyst vascularization
      and growth.

PMID- 19596833
TI  - Folic acid supplementation modifies beta-adrenoceptor-mediated in vitro lipolysis
      of obese/diabetic (+db/+db) mice.
AB  - The effects of folic acid (5.7 and 71 microg/kg, 4 weeks) consumption on the beta
      adrenoceptors (beta-ARs)-elicited lipolysis in vitro of the abdominal adipocytes
      of lean/control (+m/+db) and obese/diabetic (+db/+db) mice (female) were
      investigated. beta-AR agonists (salbutamol, a beta(2)-AR agonist; BRL 37344 and
      CGP 12177, beta(3)-AR agonists; adrenaline, a beta-AR agonist)-mediated
      lipolysis, beta(2)-, and beta(3)-ARs protein expression of the adipose tissues
      after folic acid consumption were evaluated. Our results demonstrate that a
      smaller magnitude of the basal (spontaneous) and the beta-AR agonists-triggered
      lipolysis was observed in +db/+db mice, and folic acid supplementation (71
      microg/kg) resulted in an improvement of both the baseline and the beta-ARs
      mediated lipolysis. In controls, a lower beta(2)-and beta(3)-ARs protein
      expression of the adipose tissues was detected in +db/+db mice, compared to
      +m/+db mice. In both strains fed with folic acid (71 microg/kg), a reduction of
      beta(2)-AR protein expression was observed compared to the respective controls.
      In +db/+db mice, folic acid (5.7 and 71 microg/kg) consumption caused a dose
      dependent increase of beta(3)-AR protein expression compared to controls. We
      demonstrate that lipolysis elicited by beta-AR (beta(2)- and beta(3)-ARs)
      agonists was blunted in +db/+db mice. Folic acid consumption has significant
      modulatory effects on beta-ARs protein expression and lipolysis.

PMID- 19596834
TI  - Active consent in urban elementary schools: an examination of demographic
      differences in consent rates.
AB  - The consent process is an integral piece of research and evaluation studies,
      especially when conducted within a school setting. The challenge of reaching
      parents of students to obtain consent is an issue with which those conducting
      school-based studies grapple. The literature suggests that the success of the
      consent process can affect the representativeness of the sample. This study
      describes one consent approach and examines the demographic differences between
      the eligible population, the consenters and the refusers. Demographic differences
      were found between consenters and refusers and suggestions are offered for
      further research and for other researchers who conduct school-based projects.

PMID- 19596835
TI  - Photodynamic effects of steroid-conjugated fluorophores on GABAA receptors.
AB  - We have shown that fluorescent, 7-nitro-2,1,3-benzoxadiazol-4-yl amino (NBD)
      conjugated neurosteroid analogs photopotentiate GABA(A) receptor function. These
      compounds seem to photosensitize a modification of receptor function, resulting
      in long-lived increases in responses to exogenous or synaptic GABA. Here we
      extend this work to examine the effectiveness of different fluorophore positions,
      conjugations, steroid structures, and fluorophores. Our results are generally in
      agreement with the idea that steroids with activity at GABA(A) receptors are the
      most potent photopotentiators. In particular, we find that an unnatural
      enantiomer of an effective photopotentiating steroid is relatively weak,
      excluding the idea that membrane solubility alone, which is identical for
      enantiomer pairs, is solely responsible for potent photopotentiation.
      Furthermore, there is a significant correlation between baseline GABA(A) receptor
      activity and photopotentiation. Curiously, both sulfated steroids, which bind a
      presumed external neurosteroid antagonist site, and hydroxysteroids, which bind
      an independent site, are effective. We also find that a rhodamine dye conjugated
      to a 5beta-reduced 3alpha-hydroxy steroid is a particularly potent and effective
      photopotentiator, with minimal baseline receptor activity up to 10 muM. Steroid
      conjugated fluorescein and Alexa Fluor 546 also supported photopotentiation,
      although the Alexa Fluor conjugate was weaker and required 10-fold higher
      concentration to achieve similar potentiation to the best NBD and rhodamine
      conjugates. Filling cells with steroid-conjugated or free fluorophores via whole
      cell patch pipette did not support photopotentiation. FM1-43, another membrane
      targeted, structurally unrelated fluorophore, also produced photopotentiation at
      micromolar concentrations. We conclude that further optimization of fluorophore
      and carrier could produce an effective, selective, light-sensitive GABA(A)
      receptor modulator.

PMID- 19596837
TI  - Accounting for uncertainty about investigator bias: disclosure is informative.

PMID- 19596838
TI  - Addressing conflict in strategic literature reviews: disclosure is not enough.

PMID- 19596836
TI  - Signal transducer and activator of transcription 3 is required for abnormal
      proliferation and survival of TSC2-deficient cells: relevance to pulmonary
      lymphangioleiomyomatosis.
AB  - Tumor suppressor complex TSC1/TSC2 represents a key negative regulator of
      mammalian target of rapamycin (mTOR)-S6 kinase 1 signaling. Mutational
      inactivation of TSC1 or TSC2, linked to a rare lung disease,
      lymphangioleiomyomatosis (LAM), manifests as neoplastic growth of smooth-muscle
      (SM)-like cells and cystic destruction of the lungs that induces loss of
      pulmonary function. However, the precise mechanisms of abnormal cell growth in
      LAM remain uncertain. Here, we demonstrate increased signal transducer and
      activator of transcription (STAT) 3 expression, phosphorylation, and nuclear
      localization in SM-like cells in LAM lungs and in TSC2-null xenographic tumors.
      Treatment of TSC2-null tumors with mTOR inhibitor rapamycin attenuated STAT3
      expression and phosphorylation. Increased STAT3 level and activation were also
      observed in LAM-dissociated (LAMD) cell cultures compared with normal human
      bronchus fibroblasts (HBFs) from LAM patients. Although interferon (IFN)-gamma
      inhibited proliferation of HBFs, IFN-gamma treatment had little effect on
      proliferation of LAMD and TSC2-null cells. Re-expression of TSC2 or treatment
      with rapamycin inhibited IFN-gamma-induced STAT3 phosphorylation and synergized
      with IFN-gamma in inhibiting TSC2-null and LAMD cell proliferation. Reduction of
      STAT3 protein levels or activity using specific small interfering RNA or
      inhibitory peptide, respectively, decreased proliferation and induced apoptosis
      in TSC2-null and LAMD cells and sensitized cells to growth-inhibitory and
      proapoptotic effects of IFN-gamma. Collectively, our data demonstrate that STAT3
      activation is required for proliferation and survival of cells with TSC2
      dysfunction, that STAT3 impedes growth-inhibitory and proapoptotic effects of IFN
      gamma, and that TSC2- and rapamycin-dependent inhibition of STAT3 restores
      antiproliferative effects of IFN-gamma. Thus, STAT3 may provide a novel
      therapeutic target for diseases associated with TSC1/TSC2 dysfunction.

PMID- 19596839
TI  - Conflicts of interest. How could disclosure of interests work better in medicine,
      epidemiology and public health?

PMID- 19596840
TI  - Is disclosure of potential conflicts of interest in medicine and public health
      sufficient to increase transparency and decrease corruption?

PMID- 19596841
TI  - Regulatory reinforcement of journal conflict of interest disclosures: How could
      disclosure of interests work better in medicine, epidemiology and public health?

PMID- 19596842
TI  - How could disclosure of interests work better in medicine, epidemiology and
      public health: How do potential conflicts of interest confuse medicine and public
      health?

PMID- 19596843
TI  - Human biomonitoring programmes and activities in the European Union.

PMID- 19596845
TI  - Marian Walhout: transcriptional mapmaker. Interviewed by Ben Short.

PMID- 19596846
TI  - Neuronal activity moves protein palmitoylation into the synapse.
AB  - Many neuronal proteins undergo lipid modification that regulates their function
      and subcellular localization. One such modification is palmitoylation, which is
      mediated by a large class of protein palmitoyl acyltransferases (PATs). Now, a
      paper in this issue (Noritake et al. 2009. J. Cell Biol.
      doi:10.1083/jcb.200903101) demonstrates that the localization of the PAT DHHC2 is
      regulated by neuronal activity and thereby selectively controls the
      palmitoylation and subsequent accumulation of specific proteins in the synapse.

PMID- 19596847
TI  - The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle
      stability.
AB  - Myc-induced SUN domain-containing protein (Misu or NSun2) is a nucleolar RNA
      methyltransferase important for c-Myc-induced proliferation in skin, but the
      mechanisms by which Misu contributes to cell cycle progression are unknown. In
      this study, we demonstrate that Misu translocates from the nucleoli in interphase
      to the spindle in mitosis as an RNA-protein complex that includes 18S ribosomal
      RNA. Functionally, depletion of Misu caused multiple mitotic defects, including
      formation of unstructured spindles, multipolar spindles, and chromosome
      missegregation, leading to aneuploidy and cell death. The presence of both RNA
      and Misu is required for correct spindle assembly, and this process is
      independent of active translation. Misu might mediate its function at the spindle
      by recruiting nucleolar and spindle-associated protein (NuSAP), an essential
      microtubule-stabilizing and bundling protein. We further identify NuSAP as a
      novel direct target gene of c-Myc. Collectively, our results suggest a novel
      mechanism by which c-Myc promotes proliferation by stabilizing the mitotic
      spindle in fast-dividing cells via Misu and NuSAP.

PMID- 19596848
TI  - The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton
      to adherens junctions during apical constriction.
AB  - Cadherin-based adherens junctions (AJs) mediate cell adhesion and regulate cell
      shape change. The nectin-afadin complex also localizes to AJs and links to the
      cytoskeleton. Mammalian afadin has been suggested to be essential for adhesion
      and polarity establishment, but its mechanism of action is unclear. In contrast,
      Drosophila melanogaster's afadin homologue Canoe (Cno) has suggested roles in
      signal transduction during morphogenesis. We completely removed Cno from embryos,
      testing these hypotheses. Surprisingly, Cno is not essential for AJ assembly or
      for AJ maintenance in many tissues. However, morphogenesis is impaired from the
      start. Apical constriction of mesodermal cells initiates but is not completed.
      The actomyosin cytoskeleton disconnects from AJs, uncoupling actomyosin
      constriction and cell shape change. Cno has multiple direct interactions with AJ
      proteins, but is not a core part of the cadherin-catenin complex. Instead, Cno
      localizes to AJs by a Rap1- and actin-dependent mechanism. These data suggest
      that Cno regulates linkage between AJs and the actin cytoskeleton during
      morphogenesis.

PMID- 19596849
TI  - Different Rho GTPase-dependent signaling pathways initiate sequential steps in
      the consolidation of long-term potentiation.
AB  - The releasable factor adenosine blocks the formation of long-term potentiation
      (LTP). These experiments used this observation to uncover the synaptic processes
      that stabilize the potentiation effect. Brief adenosine infusion blocked
      stimulation-induced actin polymerization within dendritic spines along with LTP
      itself in control rat hippocampal slices but not in those pretreated with the
      actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven
      phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase
      (PAK). A search for the upstream origins of these effects showed that adenosine
      suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase
      (ROCK) inhibitor reproduced adenosine's effects on cofilin phosphorylation, spine
      actin polymerization, and LTP, whereas a Rac inhibitor did not. However,
      inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by
      latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction
      initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin
      polymerization, whereas the other (Rac-PAK) stabilizes the newly formed
      filaments.

PMID- 19596850
TI  - Ca(2+) signaling evoked by activation of Na(+) channels and Na(+)/Ca(2+)
      exchangers is required for GABA-induced NG2 cell migration.
AB  - NG2 cells originate from various brain regions and migrate to their destinations
      during early development. These cells express voltage-gated Na(+) channels but
      fail to produce typical action potentials. The physiological role of Na(+)
      channels in these cells is unclear. We found that GABA induces membrane
      depolarization and Ca(2+) elevation in NG2 cells, a process requiring activation
      of GABA(A) receptors, Na(+) channels, and Na(+)/Ca(2+) exchangers (NCXs), but not
      Ca(2+) channels. We have identified a persistent Na(+) current in these cells
      that may underlie the GABA-induced pathway of prolonged Na(+) elevation, which in
      turn triggers Ca(2+) influx via NCXs. This unique Ca(2+) signaling pathway is
      further shown to be involved in the migration of NG2 cells. Thus, GABAergic
      signaling mediated by sequential activation of GABA(A) receptors, noninactivating
      Na(+) channels, and NCXs may play an important role in the development and
      function of NG2 glial cells in the brain.

PMID- 19596851
TI  - Maturation of active zone assembly by Drosophila Bruchpilot.
AB  - Synaptic vesicles fuse at active zone (AZ) membranes where Ca(2+) channels are
      clustered and that are typically decorated by electron-dense projections.
      Recently, mutants of the Drosophila melanogaster ERC/CAST family protein
      Bruchpilot (BRP) were shown to lack dense projections (T-bars) and to suffer from
      Ca(2+) channel-clustering defects. In this study, we used high resolution light
      microscopy, electron microscopy, and intravital imaging to analyze the function
      of BRP in AZ assembly. Consistent with truncated BRP variants forming shortened T
      bars, we identify BRP as a direct T-bar component at the AZ center with its N
      terminus closer to the AZ membrane than its C terminus. In contrast, Drosophila
      Liprin-alpha, another AZ-organizing protein, precedes BRP during the assembly of
      newly forming AZs by several hours and surrounds the AZ center in few discrete
      punctae. BRP seems responsible for effectively clustering Ca(2+) channels beneath
      the T-bar density late in a protracted AZ formation process, potentially through
      a direct molecular interaction with intracellular Ca(2+) channel domains.

PMID- 19596852
TI  - Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting
      of PSD-95.
AB  - Protein palmitoylation is the most common posttranslational lipid modification;
      its reversibility mediates protein shuttling between intracellular compartments.
      A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein
      palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs
      in a physiological context remain unknown. In this study, we efficiently
      monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found
      that blocking synaptic activity rapidly induces PSD-95 palmitoylation and
      mediates synaptic clustering of PSD-95 and associated AMPA (alpha-amino-3-hydroxy
      5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically
      localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive
      palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic
      density to transduce this effect. These data demonstrate that individual DHHC
      members are differentially regulated and that dynamic recruitment of protein
      palmitoylation machinery enables compartmentalized regulation of protein
      trafficking in response to extracellular signals.

PMID- 19596854
TI  - Echinoderm phosphorylated matrix proteins UTMP16 and UTMP19 have different
      functions in sea urchin tooth mineralization.
AB  - Studies of mineralization of embryonic spicules and of the sea urchin genome have
      identified several putative mineralization-related proteins. These predicted
      proteins have not been isolated or confirmed in mature mineralized tissues.
      Mature Lytechinus variegatus teeth were demineralized with 0.6 N HCl after prior
      removal of non-mineralized constituents with 4.0 M guanidinium HCl. The HCl
      extracted proteins were fractionated on ceramic hydroxyapatite and separated into
      bound and unbound pools. Gel electrophoresis compared the protein distributions.
      The differentially present bands were purified and digested with trypsin, and the
      tryptic peptides were separated by high pressure liquid chromatography. NH2
      terminal sequences were determined by Edman degradation and compared with the
      genomic sequence bank data. Two of the putative mineralization-related proteins
      were found. Their complete amino acid sequences were cloned from our L.
      variegatus cDNA library. Apatite-binding UTMP16 was found to be present in two
      isoforms; both isoforms had a signal sequence, a Ser-Asp-rich extracellular
      matrix domain, and a transmembrane and cytosolic insertion sequence. UTMP19,
      although rich in Glu and Thr did not bind to apatite. It had neither signal
      peptide nor transmembrane domain but did have typical nuclear localization and
      nuclear exit signal sequences. Both proteins were phosphorylated and good
      substrates for phosphatase. Immunolocalization studies with anti-UTMP16 show it
      to concentrate at the syncytial membranes in contact with the mineral. On the
      basis of our TOF-SIMS analyses of magnesium ion and Asp mapping of the mineral
      phase composition, we speculate that UTMP16 may be important in establishing the
      high magnesium columns that fuse the calcite plates together to enhance the
      mechanical strength of the mineralized tooth.

PMID- 19596853
TI  - Rapid purification and high sensitivity analysis of heparan sulfate from cells
      and tissues: toward glycomics profiling.
AB  - Studies on glycosaminoglycans and proteoglycans (PGs) have been hampered by
      difficulties in isolation and analysis by traditional methods that are laborious
      and lack sensitivity and throughput. Here we demonstrate a simple method for
      rapid isolation of proteoglycans (RIP) employing phenol/guanidine/chloroform
      reagent to purify heparan sulfate (HS) PGs quantitatively from various tissues
      and cells. We further show that this generic purification methodology, when
      applied in concert with a BODIPY fluorescent label, permits structural analyses
      on RIP-purified HS at approximately 1,000-fold higher sensitivity than standard
      UV detection methods and approximately 10-100-fold higher sensitivity than
      previous fluorescence detection methods. The utility of RIP-BODIPY methodology
      was demonstrated by rapid profiling of HS structural composition from small
      tissue samples, multiple mouse organs, and as little as a few thousand cultured
      cells. It was also used to generate novel insights into in vivo structural
      changes in HS from Sulf1 knock-out mice for the first time that differed
      significantly from previous observations limited to tissue culture experiments.
      RIP was also applied to purify HS for bioassay testing, exemplified by cell
      assays of fibroblast growth factor signaling activation; this generated data from
      2-O-sulfotransferase knock-out mice and revealed an unexpected deficiency in
      fibroblast growth factor activation by HS from heterozygous mice. These data
      demonstrate that RIP will underpin emerging efforts to develop glycomics
      profiling strategies for HS and other glycosaminoglycans to explore their
      structure-function relationships in complex biological systems.

PMID- 19596855
TI  - A love affair with vitamins.

PMID- 19596856
TI  - Syndecan-1 is required for robust growth, vascularization, and metastasis of
      myeloma tumors in vivo.
AB  - Myeloma tumors are characterized by high expression of syndecan-1 (CD138), a
      heparan sulfate proteoglycan present on the myeloma cell surface and shed into
      the tumor microenvironment. High levels of shed syndecan-1 in the serum of
      patients are an indicator of poor prognosis, and numerous studies have implicated
      syndecan-1 in promoting the growth and progression of this cancer. In the present
      study we directly addressed the role of syndecan-1 in myeloma by stable knockdown
      of its expression using RNA interference. Knockdown cells that were negative for
      syndecan-1 expression became apoptotic and failed to grow in vitro. Knockdown
      cells expressing syndecan-1 at approximately 28% or approximately 14% of normal
      levels survived and grew well in vitro but formed fewer and much smaller
      subcutaneous tumors in mice compared with tumors formed by cells expressing
      normal levels of syndecan-1. When injected intravenously into mice (experimental
      metastasis model), knockdown cells formed very few metastases as compared with
      controls. This indicates that syndecan-1 may be required for the establishment of
      multi-focal metastasis, a hallmark of this cancer. One mechanism of syndecan-1
      action occurs via stimulation of tumor angiogenesis because tumors formed by
      knockdown cells exhibited diminished levels of vascular endothelial growth factor
      and impaired development of blood vessels. Together, these data indicate that the
      effects of syndecan-1 on myeloma survival, growth, and dissemination are due, at
      least in part, to its positive regulation of tumor-host interactions that
      generate an environment capable of sustaining robust tumor growth.

PMID- 19596858
TI  - Induced dimerization of the amyloid precursor protein leads to decreased amyloid
      beta protein production.
AB  - The amyloid precursor protein (APP) plays a central role in Alzheimer disease
      (AD) pathogenesis because sequential cleavages by beta- and gamma-secretase lead
      to the generation of the amyloid-beta (Abeta) peptide, a key constituent in the
      amyloid plaques present in brains of AD individuals. In several studies APP has
      recently been shown to form homodimers, and this event appears to influence Abeta
      generation. However, these studies have relied on APP mutations within the Abeta
      sequence itself that may affect APP processing by interfering with secretase
      cleavages independent of dimerization. Therefore, the impact of APP dimerization
      on Abeta production remains unclear. To address this question, we compared the
      approach of constitutive cysteine-induced APP dimerization with a regulatable
      dimerization system that does not require the introduction of mutations within
      the Abeta sequence. To this end we generated an APP chimeric molecule by fusing a
      domain of the FK506-binding protein (FKBP) to the C terminus of APP. The addition
      of the synthetic membrane-permeant drug AP20187 induces rapid dimerization of the
      APP-FKBP chimera. Using this system we were able to induce up to 70% APP dimers.
      Our results showed that controlled homodimerization of APP-FKBP leads to a 50%
      reduction in total Abeta levels in transfected N2a cells. Similar results were
      obtained with the direct precursor of beta-secretase cleavage, C99/SPA4CT-FKBP.
      Furthermore, there was no modulation of different Abeta peptide species after APP
      dimerization in this system. Taken together, our results suggest that APP
      dimerization can directly affect gamma-secretase processing and that dimerization
      is not required for Abeta production.

PMID- 19596857
TI  - Mechanisms of resistance to interferon-gamma-mediated cell growth arrest in human
      oral squamous carcinoma cells.
AB  - Interferon-gamma (IFNgamma) has an antiproliferative effect on a variety of tumor
      cells. However, many tumor cells resist treatment with IFNs. Here, we show that
      IFNgamma fails to inhibit the growth of some types of oral squamous cell
      carcinoma (OSCC) cells that possess a fully functional IFNgamma/STAT1 (signal
      transducer and activator of transcription-1) signaling pathway. IFNgamma
      inhibited the growth of the HSC-2, HSC-3, and HSC-4 OSCC cell lines. However, Ca9
      22 cells were resistant to IFNgamma despite having intact STAT1-dependent
      signaling, such as normal tyrosine phosphorylation, DNA binding activity, and
      transcriptional activity of STAT1. The growth inhibition of HSC-2 cells resulted
      from S-phase arrest of the cell cycle. IFNgamma inhibited cyclin A2 (CcnA2)
      associated kinase activity, which correlated with the IFNgamma-mediated down
      regulation of CcnA2 and Cdk2 expression at both the transcriptional and post
      transcriptional level in HSC-2 cells but not in Ca9-22 cells. RNAi-mediated
      knockdown of CcnA2 and Cdk2 resulted in growth inhibition in both cell lines.
      These results indicate that the resistance of OSCC to IFNgamma is not due simply
      to the deficiency in STAT1-dependent signaling but results from a defect in the
      signaling component that mediates this IFNgamma-induced down-regulation of CcnA2
      and Cdk2 expression at the transcriptional and post-transcriptional levels.

PMID- 19596859
TI  - The developmentally regulated osteoblast phosphodiesterase GDE3 is
      glycerophosphoinositol-specific and modulates cell growth.
AB  - The glycerophosphodiester phosphodiesterase enzyme family involved in the
      hydrolysis of glycerophosphodiesters has been characterized in bacteria and
      recently identified in mammals. Here, we have characterized the activity and
      function of GDE3, one of the seven mammalian enzymes. GDE3 is up-regulated during
      osteoblast differentiation and can affect cell morphology. We show that GDE3 is a
      glycerophosphoinositol (GroPIns) phosphodiesterase that hydrolyzes GroPIns,
      producing inositol 1-phosphate and glycerol, and thus suggesting specific roles
      for this enzyme in GroPIns metabolism. Substrate specificity analyses show that
      wild-type GDE3 selectively hydrolyzes GroPIns over glycerophosphocholine,
      glycerophosphoethanolamine, and glycerophosphoserine. A single point mutation in
      the catalytic domain of GDE3 (GDE3R231A) leads to loss of GroPIns enzymatic
      hydrolysis, identifying an arginine residue crucial for GDE3 activity. After
      heterologous GDE3 expression in HEK293T cells, phosphodiesterase activity is
      detected in the extracellular medium, with no effect on the intracellular GroPIns
      pool. Together with the millimolar concentrations of calcium required for GDE3
      activity, this predicts an enzyme topology with an extracellular catalytic
      domain. Interestingly, GDE3 ectocellular activity is detected in a stable clone
      from a murine osteoblast cell line, further confirming the activity of GDE3 in a
      more physiological context. Finally, overexpression of wild-type GDE3 in
      osteoblasts promotes disassembly of actin stress fibers, decrease in growth rate,
      and increase in alkaline phosphatase activity and calcium content, indicating a
      role for GDE3 in induction of differentiation. Thus, we have identified the GDE3
      substrate GroPIns as a candidate mediator for osteoblast proliferation, in line
      with the GroPIns activity observed previously in epithelial cells.

PMID- 19596860
TI  - Mutation of asparagine 76 in the center of glutamine transporter SNAT3 modulates
      substrate-induced conductances and Na+ binding.
AB  - The glutamine transporter SLC38A3 (SNAT3) plays an important role in the release
      of glutamine from brain astrocytes and the uptake of glutamine into hepatocytes.
      It is related to the vesicular GABA (gamma-aminobutyric acid) transporter and the
      SLC36 family of proton-amino acid cotransporters. The transporter carries out
      electroneutral Na+-glutamine cotransport-H+ antiport. In addition, substrate
      induced uncoupled cation currents are observed. Mutation of asparagine 76 to
      glutamine or histidine in predicted transmembrane helix 1 abolished all substrate
      induced currents. Mutation of asparagine 76 to aspartate rendered the transporter
      Na+-independent and resulted in a gain of a large substrate-induced chloride
      conductance in the absence of Na+. Thus, a single residue is critical for coupled
      and uncoupled ion flows in the glutamine transporter SNAT3. Homology modeling of
      SNAT3 along the structure of the related benzyl-hydantoin permease from
      Microbacterium liquefaciens reveals that Asn-76 is likely to be located in the
      center of the membrane close to the translocation pore and forms part of the
      predicted Na+ -binding site.

PMID- 19596861
TI  - Distinct structures of scrapie prion protein (PrPSc)-seeded versus spontaneous
      recombinant prion protein fibrils revealed by hydrogen/deuterium exchange.
AB  - The detailed structures of prion disease-associated, partially protease-resistant
      forms of prion protein (e.g. PrP(Sc)) are largely unknown. PrP(Sc) appears to
      propagate itself by autocatalyzing the conformational conversion and
      oligomerization of normal prion protein (PrP(C)). One manifestation of PrP(Sc)
      templating activity is its ability, in protein misfolding cyclic amplification
      reactions, to seed the conversion of recombinant prion protein (rPrP) into
      aggregates that more closely resemble PrP(Sc) than spontaneously nucleated rPrP
      amyloids in terms of proteolytic fragmentation and infrared spectra. The absence
      of posttranslational modifications makes these rPrP aggregates more amenable to
      detailed structural analyses than bona fide PrP(Sc). Here, we compare the
      structures of PrP(Sc)-seeded and spontaneously nucleated aggregates of hamster
      rPrP by using H/D exchange coupled with mass spectrometry. In spontaneously
      formed fibrils, very slow H/D exchange in region approximately 163-223 represents
      a systematically H-bonded cross-beta amyloid core structure. PrP(Sc)-seeded
      aggregates have a subpopulation of molecules in which this core region extends N
      terminally as far as to residue approximately 145, and there is a significant
      degree of order within residues approximately 117-133. The formation of tightly H
      bonded structures by these more N-terminal residues may account partially for the
      generation of longer protease-resistant regions in the PrP(Sc)-seeded rPrP
      aggregates; however, part of the added protease resistance is dependent on the
      presence of SDS during proteolysis, emphasizing the multifactorial influences on
      proteolytic fragmentation patterns. These results demonstrate that PrP(Sc) has a
      distinct templating activity that induces ordered, systematically H-bonded
      structure in regions that are dynamic and poorly defined in spontaneously formed
      aggregates of rPrP.

PMID- 19596862
TI  - Relevance of fatty acid covalently bound to Escherichia coli alpha-hemolysin and
      membrane microdomains in the oligomerization process.
AB  - alpha-Hemolysin (HlyA) is an exotoxin secreted by some pathogenic strains of
      Escherichia coli that causes lysis of several mammalian cells, including
      erythrocytes of different species. HlyA is synthesized as a protoxin, pro-HlyA,
      which is activated by acylation at two internal lysines Lys-563 and Lys-689. It
      has been proposed that pore formation is the mechanism of cytolytic activity for
      this toxin, as shown in experiments with whole cells, planar lipid membranes, and
      liposomes, but these experiments have yielded conflicting results about the
      structure of the pore. In this study, HlyA cysteine replacement mutant proteins
      of amino acids have been labeled with Alexa-488 and Alexa-546. Fluorescence
      resonance energy transfer measurements, employing labeled toxin bound to sheep
      ghost erythrocytes, have demonstrated that HlyA oligomerizes on erythrocyte
      membranes. As the cytotoxic activity is absolutely dependent on acylation, we
      have studied the role of acylation in the oligomerization, demonstrating that
      fatty acids are essential in this process. On the other hand, fluorescence
      resonance energy transfer and the hemolytic activity decrease when the
      erythrocyte ghosts are cholesterol-depleted, hence indicating the role of
      membrane microdomains in the clustering of HlyA. Simultaneously, HlyA was found
      in detergent-resistant membranes. Pro-HlyA has also been found in detergent
      resistant membranes, thus demonstrating that the importance of acyl chains in
      toxin oligomerization is the promotion of protein-protein interaction. These
      results change the concept of the main role assigned to acyl chain in the
      targeting of proteins to membrane microdomains.

PMID- 19596864
TI  - The choking game and YouTube: a dangerous combination.
AB  - PURPOSE: To study postings of partial asphyxiation by adolescents on YouTube and
      to increase awareness of this dangerous activity as well as the value of YouTube
      as a research tool. METHODS: Videos were searched on YouTube using many terms for
      recreational partial asphyxiation. Data were gathered on the participants and on
      the occurrence of hypoxic seizure. RESULTS: Sixty-five videos of the asphyxiation
      game were identified. Most (90%) participants were male. A variety of techniques
      were used. Hypoxic seizures were witnessed in 55% of videos, but occurred in 88%
      of videos that employed the "sleeper hold" technique. The videos were
      collectively viewed 173550 times on YouTube. CONCLUSIONS: YouTube has enabled
      millions of young people to watch videos of the "choking game" and other
      dangerous activities. Seeing videos may normalize the behavior among adolescents.
      Increased awareness of this activity may prevent some youths from participating
      and potentially harming themselves or others.

PMID- 19596865
TI  - Outcomes of late-preterm infants: a retrospective, single-center, Canadian study.
AB  - OBJECTIVE: To study the prevalence of major morbidities and mortality of inborn,
      late-preterm infants. Methods. A retrospective review was conducted from 2004 to
      2008. Descriptive outcomes were compared with predefined aggregate outcomes of
      term infants during the same period. RESULTS: Data on 1193 late-preterm and 8666
      term infants were compared. Majority of late-preterm infants were 36 weeks
      (43.6%), followed by 35 weeks (29.2%) and 34 weeks (27.2%), respectively. The
      prevalence of intensive care admission, respiratory support, pneumothorax, and
      mortality in late preterm infants was significantly higher compared with term
      infants. Mechanical ventilation and continuous positive airway pressure rates
      substantially decreased with increased gestational age. Although only 1.0% had
      positive cultures, 28.5% received parenteral antibiotics. The late-preterm group
      had a 12-fold higher risk of death with an overall mortality rate of 0.8%.
      CONCLUSION: This study confirmed the high-risk status of late-preterm infants
      with worse mortality and morbidities compared with term infants.

PMID- 19596863
TI  - Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory
      compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl.
AB  - The protozoan parasite Toxoplasma gondii relies on post-translational
      modification, including proteolysis, of proteins required for recognition and
      invasion of host cells. We have characterized the T. gondii cysteine protease
      cathepsin L (TgCPL), one of five cathepsins found in the T. gondii genome. We
      show that TgCPL is the primary target of the compound morpholinurea-leucyl
      homophenyl-vinyl sulfone phenyl (LHVS), which was previously shown to inhibit
      parasite invasion by blocking the release of invasion proteins from microneme
      secretory organelles. As shown by fluorescently labeled LHVS and TgCPL-specific
      antibodies, TgCPL is associated with a discrete vesicular structure in the apical
      region of extracellular parasites but is found in multiple puncta throughout the
      cytoplasm of intracellular replicating parasites. LHVS fails to label cells
      lacking TgCPL due to targeted disruption of the TgCPL gene in two different
      parasite strains. We present a structural model for the inhibition of TgCPL by
      LHVS based on a 2.0 A resolution crystal structure of TgCPL in complex with its
      propeptide. We discuss possible roles for TgCPL as a protease involved in the
      degradation or limited proteolysis of parasite proteins involved in invasion.

PMID- 19596866
TI  - Risk-taking behaviors among vertically HIV-infected adolescents in northern
      Thailand.
AB  - PURPOSE: To examine risk-taking behaviors and HIV self-disclosure among
      vertically HIV-infected adolescents in northern Thailand. METHODS: A quantitative
      survey was conducted from 2007 to 2008 at 2 pediatric HIV clinics in northern
      Thailand among vertically HIV-infected adolescents aged > or =13 years, with
      disclosed HIV status. The survey assessed sociodemographics, substance use,
      sexual behavior, peer behaviors, knowledge, and attitudes regarding HIV
      disclosure. RESULTS: Fifty-four adolescents (median age 14.6 years) participated;
      18.5% reported previous alcohol use but none reported drug use; 35.2% reported
      presexual activity, and 3.7% reported sexual activity. Nearly all (96.3%) knew
      that HIV could be transmitted sexually, but knowledge regarding other sexually
      transmitted infections (STIs) was poor. Nearly half (48.1%) had never disclosed
      their status to anyone. CONCLUSIONS: Rates of substance use and sexual activity
      were low in this population. STI knowledge was poor and diagnosis self-disclosure
      was infrequent. Improved sexual education and self-disclosure skills are needed
      among vertically HIV-infected adolescents in Thailand.

PMID- 19596867
TI  - Effects of categorizing continuous variables in decision-analytic models.
AB  - PURPOSE: When using continuous predictor variables in discrete-state Markov
      modeling, it is necessary to create categories of risk and assume homogeneous
      disease risk within categories, which may bias model outcomes. This analysis
      assessed the tradeoffs between model bias and complexity and/or data limitations
      when categorizing continuous risk factors in Markov models. METHODS: The authors
      developed a generic Markov cohort model of disease, defining bias as the
      percentage change in life expectancy gain from a hypothetical intervention when
      using 2 to 15 risk factor categories as compared with modeling the risk factor as
      a continuous variable. They evaluated the magnitude and sign of bias as a
      function of disease incidence, disease-specific mortality, and relative
      difference in risk among categories. RESULTS: Bias was positive in the base case,
      indicating that categorization overestimated life expectancy gains. The bias
      approached zero as the number of risk factor categories increased and did not
      exceed 4% for any parameter combinations or numbers of categories considered. For
      any given disease-specific mortality and disease incidence, bias increased with
      relative risk of disease. For any given relative risk, the relationship between
      bias and parameters such as disease-specific mortality or disease incidence was
      not always monotonic. CONCLUSIONS: Under the assumption of a normally distributed
      risk factor and reasonable assumption regarding disease risk and moderate values
      for the relative risk of disease given risk factor category, categorizing
      continuously valued risk factors in Markov models is associated with less than 4%
      absolute bias when at least 2 categories are used.

PMID- 19596868
TI  - High-throughput screening identifies three inhibitor classes of the telomere
      resolvase from the lyme disease spirochete.
AB  - Lyme disease, the most common vector-borne zoonosis in North America, is caused
      by the spirochetal pathogen Borrelia burgdorferi. The telomere resolvase encoded
      by this organism (ResT) promotes the formation of covalently closed hairpin ends
      on the linear DNA molecules of B. burgdorferi through a two-step
      transesterification. ResT is essential for survival and is therefore an
      attractive target for the development of highly specific antiborrelial drugs. To
      identify ResT inhibitors, a novel fluorescence-based high-throughput assay was
      developed and used to screen a library of 27,520 small-molecule drug-like
      compounds. Six confirmed inhibitors of ResT, with 50% inhibitory concentrations
      between 2 and 10 muM, were identified. The inhibitors were characterized further
      and were grouped into three distinct classes based on their inhibitory features.
      The high-throughput screening assay developed in this paper, along with the six
      inhibitory compounds identified, provides a starting point for the future
      development of novel antiborrelial drugs as well as small-molecule inhibitors
      that will be helpful for the further dissection of the reaction mechanism.

PMID- 19596869
TI  - Improved murine model of malaria using Plasmodium falciparum competent strains
      and non-myelodepleted NOD-scid IL2Rgammanull mice engrafted with human
      erythrocytes.
AB  - Murine models of Plasmodium falciparum malaria may become crucial tools in drug
      discovery. Here we show that non-myelodepleted NOD-scid IL2Rgamma(null) mice
      engrafted with human erythrocytes support an infectious burden up to tenfold
      higher than that supported by engrafted NOD-scid beta2microglobulin(null) mice.
      The new model was validated for drug discovery and was used to assess the
      therapeutic efficacy of 4-pyridones, selective inhibitors of P. falciparum
      cytochrome bc1.

PMID- 19596870
TI  - Identification of the aminoglycoside resistance determinants armA and rmtC among
      non-Typhi Salmonella isolates from humans in the United States.

PMID- 19596871
TI  - Diversity of beta-lactamases produced by ceftazidime-resistant Pseudomonas
      aeruginosa isolates causing bloodstream infections in Brazil.
AB  - A retrospective survey was conducted to characterize beta-lactamases in a
      collection of 43 ceftazidime-resistant Pseudomonas aeruginosa isolates recovered
      from patients with bloodstream infections hospitalized at a Brazilian teaching
      hospital between January and December 2005. Resistance rates for carbapenems,
      aminoglycosides, and quinolones were over 80%, with only colistin remaining
      active against all isolates. Pulsed-field gel electrophoresis analysis identified
      seven different genotypes. AmpC overproduction was found to be the sole beta
      lactamase-mediated mechanism responsible for ceftazidime resistance in four
      isolates (9.3%). Nine isolates (20.9%) produced an extended-spectrum beta
      lactamase (ESBL), either GES-1 (n = 7, 16.3%) or CTX-M-2 (n = 2, 4.6%).
      Carbapenemase activity was detected in 30 (70%) additional isolates. Among those
      isolates, two isolates (4.6%) produced the ESBL GES-5, possessing the ability to
      hydrolyze imipenem; a single isolate (2.3%) produced the metallo-beta-lactamase
      (MBL) IMP-1; and 27 isolates produced the MBL SPM-1 (62.8%). None of the isolates
      coproduced both ESBL and MBL. Insertion sequence elements ISCR4 and ISCR1 were
      associated with bla(SPM-1) and bla(CTX-M-2) genes, respectively, whereas the
      bla(GES-1) and bla(GES-5) genes were part of class 1 integron structures. This
      study underlines the spread of MBL- and ESBL-producing P. aeruginosa isolates as
      an important source of ceftazidime resistance in Brazil.

PMID- 19596872
TI  - In vitro trafficking and efficacy of core-shell nanostructures for treating
      intracellular Salmonella infections.
AB  - Nanostructures encapsulating gentamicin and having either amphiphilic (N1) or
      hydrophilic (N2) surfaces were designed. Flow cytometry and confocal microscopy
      studies demonstrated a higher rate of uptake for amphiphilic surfaces. A majority
      of N1 were localized in the cytoplasm, whereas N2 colocalized with the
      endosomes/lysosomes. Colocalization was not observed between nanostructures and
      intracellular Salmonella bacteria. However, significant in vitro reductions in
      bacterial counts (0.44 log10) were observed after incubation with N1, suggesting
      that the surface property of the nanostructure influences intracellular bacterial
      clearance.

PMID- 19596873
TI  - AI-2/LuxS is involved in increased biofilm formation by Streptococcus intermedius
      in the presence of antibiotics.
AB  - Bacteria utilize quorum-sensing communication to organize their behavior by
      monitoring the concentration of bacterial signals, referred to as autoinducers
      (AIs). The widespread detection of AI-2 signals and its enzymatic synthase (LuxS)
      in bacteria suggests that AI-2 is an inter- and intraspecies communication
      signal. We have previously shown that antibiotic susceptibility is affected by AI
      2 signaling in Streptococcus anginosus. Since chronic infections involve
      persistent biofilms resilient to antibiotic treatment, we explored the role of AI
      2/LuxS in Streptococcus intermedius biofilm formation and cell viability when the
      organism was exposed to sub-MICs of ampicillin, ciprofloxacin, or tetracycline.
      The S. intermedius wild type (WT) and its isogenic luxS mutant, strain SI006,
      were exposed to sub-MICs of ampicillin, ciprofloxacin, or tetracycline. Biofilms
      were formed on polystyrene discs in microtiter plates. To assess planktonic cell
      viability, the ATP microbial viability assay was performed and the numbers of CFU
      were determined. For complementation assays, the AI-2 precursor dihydroxy
      pentanedione (DPD) was used as a supplement for SI006. Relative luxS expression
      was quantified by real-time PCR. The sub-MICs of all three antibiotics increased
      biofilm formation in S. intermedius WT. However, biofilm formation by SI006 was
      either unaffected or reduced (P < or = 0.05). Bacterial viability tests of
      biofilm and planktonic cell cultures indicated that SI006 was more susceptible to
      antibiotics than the WT. DPD complemented the luxS mutant phenotype. Real-time
      PCR revealed modest yet significant changes in luxS expression in the presence of
      antibiotic concentrations that increased biofilm formation. In conclusion, in S.
      intermedius, AI-2/LuxS was involved in antibiotic susceptibility and increased
      biofilm formation at sub-MICs of antibiotic.

PMID- 19596874
TI  - Use of different inhibitory quotients to predict early virological response to
      tipranavir in antiretroviral-experienced human immunodeficiency virus-infected
      patients.
AB  - Information about the relationship between pharmacological parameters and an
      early virological response to tipranavir (TPV) is scarce. Human immunodeficiency
      virus (HIV)-infected patients who had received TPV as part of a salvage regimen
      were analyzed retrospectively. A virological response was defined as a decline in
      the HIV RNA level of > or = 1 log unit or to <50 copies/ml between weeks 4 and 12
      of therapy. The virtual inhibitory quotient (vIQ) was calculated as the ratio of
      the TPV plasma trough concentration (C(trough))/virtual change in the 50%
      inhibitory concentration. Three genotypic inhibitory quotients (gIQs) were
      calculated by using different TPV resistance mutation scores (from the
      International AIDS Society-USA [IAS-USA], Randomized Evaluation of Strategic
      Intervention in Multidrug-Resistant Patients with Tipranavir [RESIST], and Agence
      Nationale de Recherches sur le Sida et les Hepatites Virales [ANRS] trials). The
      sensitivities, specificities, positive predictive values (PPVs), negative
      predictive values (NPVs), and likelihood ratios for a positive result (LHR+) and
      a negative result (LHR-) [LHR+ = sensitivity/(1-specificity); LHR- = (1
      sensitivity)/specificity] were calculated. A total of 57 HIV-infected patients
      were analyzed. A virological response was achieved by 77% of the patients. TPV
      resistance mutations, TPV C(trough), vIQs, and gIQs were all significantly
      associated with a virological response. The vIQ had the best PPV and NPV (97% and
      78%, respectively). The values of the LHR+ were 7.8 for vIQ, 3.4 for the RESIST
      gIQ, 3.3 for the IAS-USA gIQ, 3.1 for the ANRS gIQ, 2.2 for TPV C(trough), and
      1.3 for the IAS-USA and RESIST scores. The values of LHR- were 0 for the RESIST
      score, 0.07 for vIQ, 0.09 for the IAS-USA score, 0.27 for the RESIST gIQ, 0.32
      for the IAS-USA gIQ, 0.37 for the ANRS gIQ, and 0.48 for TPV C(trough). HIV
      infected patients who initiate a salvage regimen based on TPV may benefit from
      baseline drug resistance testing and TPV plasma concentration determination, as
      vIQ is the best predictor of a virological response.

PMID- 19596875
TI  - Comparative efficacy and safety of vancomycin versus teicoplanin: systematic
      review and meta-analysis.
AB  - Vancomycin and teicoplanin are the glycopeptides currently in use for the
      treatment of infections caused by invasive beta-lactam-resistant gram-positive
      organisms. We conducted a systematic review and meta-analysis of randomized
      controlled trials that have compared vancomycin and teicoplanin administered
      systemically for the treatment of suspected or proven infections. A comprehensive
      search of trials without year, language, or publication status restrictions was
      performed. The primary outcome was all-cause mortality. Two reviewers
      independently extracted the data. Risk ratios (RRs) with 95% confidence intervals
      (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin).
      Twenty-four trials were included. All-cause mortality was similar overall (RR,
      0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In
      trials that used adequate allocation concealment, the results favored teicoplanin
      (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or
      inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to
      10.30). The latter trials might have recruited more severely ill patients. No
      other variable affected the RRs for mortality, including the assessment of
      glycopeptides administered empirically or for proven infections, neutropenia, the
      participant's age, and drug dosing. There were no significant differences between
      teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI,
      0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and
      other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure
      were observed with a lower risk of bias and when treatment was initiated for
      infections caused by gram-positive organisms rather than empirically. Total
      adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95%
      CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with
      teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy
      and is associated with a lower adverse event rate than vancomycin.

PMID- 19596876
TI  - In vivo characterization of the peptide deformylase inhibitor LBM415 in murine
      infection models.
AB  - LBM415 is an antibacterial agent belonging to the peptide deformylase inhibitor
      class of compounds. It has previously been shown to demonstrate good activity in
      vitro against a range of pathogens. In this study, the in vivo efficacy of LBM415
      was evaluated in various mouse infection models. We investigated activity against
      a systemic infection model caused by intraperitoneal inoculation of
      Staphylococcus aureus (methicillin [meticillin] susceptible [MSSA] and
      methicillin resistant [MRSA]) and Streptococcus pneumoniae (penicillin
      susceptible [PSSP] and multidrug resistant [MDRSP]), a thigh infection model
      caused by intramuscular injection of MRSA, and a lung infection produced by
      intranasal inoculation of PSSP. In the systemic MSSA and MRSA infections, LBM415
      was equivalent to linezolid and vancomycin. In the systemic PSSP infection,
      LBM415 was equivalent to linezolid, whereas against systemic MDRSP infection, the
      LBM415 50% effective dose (ED50) was 4.8 mg/kg (dosed subcutaneously) and 36.6
      mg/kg (dosed orally), compared to 13.2 mg/kg for telithromycin and >60 mg/kg for
      penicillin V and clarithromycin. In the MRSA thigh infection, LBM415
      significantly reduced thigh bacterial levels compared to those of untreated mice,
      with levels similar to those after treatment with linezolid at the same dose
      levels. In the pneumonia model, the ED50 to reduce the bacterial lung burden by
      >4 log10 in 50% of treated animals was 23.3 mg/kg for LBM415, whereas
      moxifloxacin showed an ED50 of 14.3 mg/kg. In summary, LBM415 showed in vivo
      efficacy in sepsis and specific organ infection models irrespective of resistance
      to other antibiotics. Results suggest the potential of peptide deformylase
      inhibitors as a novel class of therapeutic agents against antibiotic-resistant
      pathogens.

PMID- 19596877
TI  - Staphylococcus aureus mutant screen reveals interaction of the human
      antimicrobial peptide dermcidin with membrane phospholipids.
AB  - Antimicrobial peptides (AMPs) form an important part of the innate host defense.
      In contrast to most AMPs, human dermcidin has an anionic net charge. To
      investigate whether bacteria have developed specific mechanisms of resistance to
      dermcidin, we screened for mutants of the leading human pathogen, Staphylococcus
      aureus, with altered resistance to dermcidin. To that end, we constructed a
      plasmid for use in mariner-based transposon mutagenesis and developed a high
      throughput cell viability screening method based on luminescence. In a large
      screen, we did not find mutants with strongly increased susceptibility to
      dermcidin, indicating that S. aureus has no specific mechanism of resistance to
      this AMP. Furthermore, we detected a mutation in a gene of unknown function that
      resulted in significantly increased resistance to dermcidin. The mutant strain
      had an altered membrane phospholipid pattern and showed decreased binding of
      dermcidin to the bacterial surface, indicating that dermcidin interacts with
      membrane phospholipids. The mode of this interaction was direct, as shown by
      assays of dermcidin binding to phospholipid preparations, and specific, as the
      resistance to other AMPs was not affected. Our findings indicate that dermcidin
      has an exceptional value for the human innate host defense and lend support to
      the idea that it evolved to evade bacterial resistance mechanisms targeted at the
      cationic character of most AMPs. Moreover, they suggest that the antimicrobial
      activity of dermcidin is dependent on the interaction with the bacterial membrane
      and might thus assist with the determination of the yet unknown mode of action of
      this important human AMP.

PMID- 19596879
TI  - Pharmacodynamics of vancomycin at simulated epithelial lining fluid
      concentrations against methicillin-resistant Staphylococcus aureus (MRSA):
      implications for dosing in MRSA pneumonia.
AB  - Little is known regarding killing activity of vancomycin against methicillin
      (meticillin)-resistant Staphylococcus aureus (MRSA) in pneumonia since the extent
      of vancomycin penetration into epithelial lining fluid (ELF) has not been
      definitively established. We evaluated the impact of the extent of ELF
      penetration on bacterial killing and resistance by simulating a range of
      vancomycin exposures (24-h free drug area under the concentration-time curve
      [fAUC24]/MIC) using an in vitro pharmacodynamic model and population-based
      mathematical modeling. A high-dose, 1.5-g-every-12-h vancomycin regimen according
      to American Thoracic Society/Infectious Diseases Society of America guidelines
      (trough concentration, 15 mg/liter) with simulated ELF/plasma penetration of 0,
      20, 40, 60, 80, or 100% (fAUC24/MIC of 0, 70, 140, 210, 280, or 350) was
      evaluated against two agr-functional, group II MRSA clinical isolates obtained
      from patients with a bloodstream infection (MIC = 1.0 mg/liter) at a high
      inoculum of 10(8) CFU/ml. Despite high vancomycin exposures and 100% penetration,
      all regimens up to a fAUC24/MIC of 350 did not achieve bactericidal activity. At
      regimens of < or = 60% penetration (fAUC24/MIC < or = 210), stasis and regrowth
      occurred, amplifying the development of intermediately resistant subpopulations.
      Regimens simulating > or = 80% penetration (fAUC24/MIC > or = 280) suppressed
      development of resistance. Resistant mutants amplified by suboptimal vancomycin
      exposure displayed reduced rates of autolysis (Triton X-100) at 72 h. Bacterial
      growth and death were well characterized by a Hill-type model (r2 > or = 0.984)
      and a population pharmacodynamic model with a resistant and susceptible
      subpopulation (r2 > or = 0.965). Due to the emergence of vancomycin-intermediate
      resistance at a fAUC24/MIC of < or = 210, exceeding this exposure breakpoint in
      ELF may help to guide optimal dosage regimens in the treatment of MRSA pneumonia.

PMID- 19596878
TI  - The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium
      tuberculosis.
AB  - Ethambutol (EMB) is an antimycobacterial drug used extensively for the treatment
      of tuberculosis caused by Mycobacterium tuberculosis. EMB targets the
      biosynthesis of the cell wall, inhibiting the synthesis of both arabinogalactan
      and lipoarabinomannan (LAM), and is assumed to act via inhibition of three
      arabinosyltransferases: EmbA, EmbB, and EmbC. EmbA and EmbB are required for the
      synthesis of arabinogalactan, and at least one enzyme (M. tuberculosis EmbA
      [EmbA(Mt)]) is essential in M. tuberculosis. EmbC(Mt) is also essential for the
      viability of M. tuberculosis but is involved in the synthesis of LAM. We show
      that mutations in EmbC(Mt) that reduce its arabinosyltransferase activity result
      in increased sensitivity to EMB and the production of smaller LAM species in M.
      tuberculosis. Overexpression of EmbC(Mt) was not tolerated in M. tuberculosis,
      but overexpression of Mycobacterium smegmatis EmbC (EmbC(Ms)) led to EMB
      resistance and the production of larger LAM species in M. tuberculosis. Treatment
      of wild-type M. tuberculosis strains with EMB led to inhibition of LAM synthesis,
      resulting in the production of smaller species of LAM. In contrast, no change in
      LAM production was seen in EMB-resistant strains. Overexpression of EmbB(Ms) in
      M. tuberculosis also resulted in EMB resistance, but at a lower level than that
      caused by EmbC(Ms). Overexpression of EmbA(Mt) in M. tuberculosis had no effect
      on EMB resistance. Thus, there is a direct correlation between EmbC activity and
      EMB resistance, as well as between EmbC activity and the size of the LAM species
      produced, confirming that EmbC is one of the cellular targets of EMB action.

PMID- 19596880
TI  - Mechanisms of resistance in nontyphoidal Salmonella enterica strains exhibiting a
      nonclassical quinolone resistance phenotype.
AB  - Nontyphoidal Salmonella enterica strains with a nonclassical quinolone resistance
      phenotype were isolated from patients returning from Thailand or Malaysia to
      Finland. A total of 10 isolates of seven serovars were studied in detail, all of
      which had reduced susceptibility (MIC > or = 0.125 microg/ml) to ciprofloxacin
      but were either susceptible or showed only low-level resistance (MIC < or = 32
      microg/ml) to nalidixic acid. Phenotypic characterization included susceptibility
      testing by the agar dilution method and investigation of efflux activity.
      Genotypic characterization included the screening of mutations in the quinolone
      resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE by PCR and
      denaturing high-pressure liquid chromatography and the amplification of plasmid
      mediated quinolone resistance (PMQR) genes qnrA, qnrB, qnrS, qnrD, aac(6')-Ib-cr,
      and qepA by PCR. PMQR was confirmed by plasmid analysis, Southern hybridization,
      and plasmid transfer. No mutations in the QRDRs of gyrA, gyrB, parC, or parE were
      detected with the exception of a Thr57-Ser substitution within ParC seen in all
      but the S. enterica serovar Typhimurium strains. The qnrA and qnrS genes were the
      only PMQR determinants detected. Plasmids carrying qnr alleles were transferable
      in vitro, and the resistance phenotype was reproducible in Escherichia coli
      DH5alpha transformants. These data demonstrate the emergence of a highly mobile
      qnr genotype that, in the absence of mutation within topoisomerase genes, confers
      the nontypical quinolone resistance phenotype in S. enterica isolates. The qnr
      resistance mechanism enables bacteria to survive elevated quinolone
      concentrations, and therefore, strains carrying qnr alleles may be able to expand
      during fluoroquinolone treatment. This is of concern since nonclassical quinolone
      resistance is plasmid mediated and therefore mobilizable.

PMID- 19596881
TI  - Effect of beta-1,6-glucan inhibitors on the invasion process of Candida albicans:
      potential mechanism of their in vivo efficacy.
AB  - Beta-1,6-glucan is a fungus-specific cell wall component that is essential for
      the retention of many cell wall proteins. We recently reported the discovery of a
      small molecule inhibitor of beta-1,6-glucan biosynthesis in yeasts. In the course
      of our study of its derivatives, we found a unique feature in their antifungal
      profile. D21-6076, one of these compounds, exhibited potent in vitro and in vivo
      antifungal activities against Candida glabrata. Interestingly, although it only
      weakly reduced the growth of Candida albicans in conventional media, it
      significantly prolonged the survival of mice infected by the pathogen.
      Biochemical evaluation of D21-6076 indicated that it inhibited beta-1,6-glucan
      synthesis of C. albicans, leading the cell wall proteins, which play a critical
      role in its virulence, to be released from the cell. Correspondingly, adhesion of
      C. albicans cells to mammalian cells and their hyphal elongation were strongly
      reduced by the drug treatment. The results of the experiment using an in vitro
      model of vaginal candidiasis showed that D21-6076 strongly inhibited the invasion
      process of C. albicans without a significant reduction in its growth in the
      medium. These evidences suggested that D21-6076 probably exhibited in vivo
      efficacy against C. albicans by inhibiting its invasion process.

PMID- 19596882
TI  - Antimalarial activity of tigecycline, a novel glycylcycline antibiotic.
AB  - Tigecycline is a novel glycylcycline antibiotic with a broad antibacterial
      spectrum. Tigecycline was tested with 66 clinical isolates of Plasmodium
      falciparum from Bangladesh using the histidine-rich protein 2 in vitro drug
      susceptibility assay. The 50% and 90% inhibitory concentrations of tigecycline
      were 699 (95% confidence interval, 496 to 986) and 5,905 nM (4,344 to 8,028).
      Tigecycline shows no activity correlation with traditional antimalarials and has
      substantial antimalarial activity on its own.

PMID- 19596883
TI  - Lipoprotein processing is essential for resistance of Mycobacterium tuberculosis
      to malachite green.
AB  - Malachite green, a synthetic antimicrobial dye, has been used for over 50 years
      in mycobacterial culture medium to inhibit the growth of contaminants. The
      molecular basis of mycobacterial resistance to malachite green is unknown,
      although the presence of malachite green-reducing enzymes in the cell envelope
      has been suggested. The objective of this study was to investigate the role of
      lipoproteins in resistance of Mycobacterium tuberculosis to malachite green. The
      replication of an M. tuberculosis lipoprotein signal peptidase II (lspA) mutant
      (DeltalspA::lspAmut) on Middlebrook agar with and without 1 mg/liter malachite
      green was investigated. The lspA mutant was also compared with wild-type M.
      tuberculosis in the decolorization rate of malachite green and sensitivity to
      sodium dodecyl sulfate (SDS) detergent and first-line antituberculosis drugs. The
      lspA mutant has a 10(4)-fold reduction in CFU-forming efficiency on Middlebrook
      agar with malachite green. Malachite green is decolorized faster in the presence
      of the lspA mutant than wild-type bacteria. The lspA mutant is hypersensitive to
      SDS detergent and shows increased sensitivity to first-line antituberculosis
      drugs. In summary, lipoprotein processing by LspA is essential for resistance of
      M. tuberculosis to malachite green. A cell wall permeability defect is likely
      responsible for the hypersensitivity of lspA mutant to malachite green.

PMID- 19596884
TI  - Differential expression of ccrA in methicillin-resistant Staphylococcus aureus
      strains carrying staphylococcal cassette chromosome mec type II and IVa elements.
AB  - Excision of staphylococcal cassette chromosome mec (SCCmec) is mediated through
      the ccrA- and -B-encoded recombinases. We investigated the effects of different
      antimicrobial agents on ccrA expression by using a ccrA::lacZ fusion and reverse
      transcription-PCR with methicillin (meticillin)-resistant Staphylococcus aureus
      strains MW2 (SCCmec IVa) and N315 (SCCmec II). Upregulation of ccrA was observed
      upon exposure to beta-lactam antibiotics. Vancomycin increased ccrA expression in
      MW2 but had no effect on N315. Vancomycin may contribute to the transfer of
      SCCmec IVa but have no effect in SCCmec II.

PMID- 19596885
TI  - Anti-human immunodeficiency virus activity, cross-resistance, cytotoxicity, and
      intracellular pharmacology of the 3'-azido-2',3'-dideoxypurine nucleosides.
AB  - Although the approved nucleoside reverse transcriptase (RT) inhibitors (NRTI) are
      integral components of therapy for human immunodeficiency virus type 1 (HIV-1)
      infection, they can have significant limitations, including the selection of NRTI
      resistant HIV-1 and cellular toxicity. Accordingly, there is a critical need to
      develop new NRTI that have excellent activity and safety profiles and exhibit
      little or no cross-resistance with existing drugs. In this study, we report that
      the 3'-azido-2',3'-dideoxypurine nucleosides (ADPNs) 3'-azido-2',3'
      dideoxyadenosine (3'-azido-ddA) and 3'-azido-2',3'-dideoxyguanosine (3'-azido
      ddG) exert potent antiviral activity in primary human lymphocytes and HeLa and T
      cell lines (50% inhibitory concentrations [IC50s] range from 0.19 to 2.1 microM
      for 3'-azido-ddG and from 0.36 to 10 microM for 3'-azido-ddA) and that their
      triphosphate forms are incorporated as efficiently as the natural dGTP or dATP
      substrates by HIV-1 RT. Importantly, both 3'-azido-ddA and 3'-azido-ddG retain
      activity against viruses containing K65R, L74V, or M184V (IC50 change of <2.0
      fold) and against those containing three or more thymidine analog mutations (IC50
      change of <3.5-fold). In addition, 3'-azido-ddG does not exhibit cytotoxicity in
      primary lymphocytes or epithelial or T-cell lines and does not decrease the
      mitochondrial DNA content of HepG2 cells. Furthermore, 3'-azido-ddG is
      efficiently phosphorylated to 3'-azido-ddGTP in human lymphocytes, with an
      intracellular half-life of the nucleoside triphosphate of 9 h. The present data
      suggest that additional preclinical studies are warranted to assess the potential
      of ADPNs for treatment of HIV-1 infection.

PMID- 19596887
TI  - In vitro activities of trioxaquines against Schistosoma mansoni.
AB  - We report the in vitro activities of trioxaquines against larval and adult-stage
      schistosomes at 5 and 50 microg/ml, respectively. Such activities are equivalent
      to that of praziquantel, the major and rather unique drug currently used for the
      treatment of schistosomiasis. In this range of concentrations, artemisinin
      derivatives (artesunate and artemether) have no activity.

PMID- 19596886
TI  - DAS181 inhibits H5N1 influenza virus infection of human lung tissues.
AB  - DAS181 is a novel candidate therapeutic agent against influenza virus which
      functions via the mechanism of removing the virus receptor, sialic acid (Sia),
      from the adjacent glycan structures. DAS181 and its analogues have previously
      been shown to be potently active against multiple strains of seasonal and avian
      influenza virus strains in several experimental models, including cell lines,
      mice, and ferrets. Here we demonstrate that DAS181 treatment leads to
      desialylation of both alpha2-6-linked and alpha2-3-linked Sia in ex vivo human
      lung tissue culture and primary pneumocytes. DAS181 treatment also effectively
      protects human lung tissue and pneumocytes against the highly pathogenic avian
      influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given
      12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue
      culture. These findings support the potential value of DAS181 as a broad-spectrum
      therapeutic agent against influenza viruses, especially H5N1.

PMID- 19596888
TI  - Exploring the mode of action of antimicrobial peptide MUC7 12-mer by fitness
      profiling of Saccharomyces cerevisiae genomewide mutant collection.
AB  - The MUC7 12-mer (RKSYKCLHKRCR) is a cationic antimicrobial peptide derived from
      the human salivary mucin MUC7. To study its effect/mechanism of action on fungi,
      we performed a fitness screen of a tagged, diploid, homozygous gene deletion
      mutant pool of the yeast Saccharomyces cerevisiae grown in the presence of the
      MUC7 peptide. Forty-five strains exhibiting reduced fitness and 13 strains
      exhibiting increased fitness (sensitivity or resistance, respectively) were
      identified by hybridization intensities to tag arrays. The strongest fitness
      defects were observed with deletions in genes encoding elements of the RIM101
      signaling pathway (regulating response to alkaline and neutral pH and other
      environmental conditions) and of the endosomal sorting complex required for
      transport (ESCRT; functioning mainly in protein sorting for degradation, but also
      required for activation of the RIM101 pathway). Other deletions identified as
      conferring fitness defect or gain are in genes associated with a variety of
      functions, including transcription regulation, protein trafficking, transport,
      metabolism, and others. The results of the pool fitness screen were validated by
      a set of mutant strains tested individually in the presence of the MUC7 12-mer.
      All tested RIM101-related deletion strains showing fitness defects confirmed
      their sensitivities. Taken together, the results led us to conclude that
      deletions of genes associated with the RIM101 pathway confer sensitivity to the
      peptide by preventing activation of this pathway and that this stress response
      plays a major role in the protection of S. cerevisiae against damage inflicted by
      the MUC7 12-mer peptide.

PMID- 19596889
TI  - Genetic context of plasmid-carried blaCMY-2-like genes in Enterobacteriaceae.
AB  - Analysis of 15 European clinical Enterobacteriaceae isolates showed that
      differences in the genetic context of blaCMY-2-like genes reflected the replicon
      type, usually IncA/C or IncI1. These blaCMY-2 loci may originate from the same
      ISEcp1-mediated mobilization from the Citrobacter freundii chromosome as
      structures described in earlier studies.

PMID- 19596890
TI  - Anidulafungin in combination with amphotericin B against Aspergillus fumigatus.
AB  - We investigated the effects of anidulafungin alone and in combination with
      amphotericin B against Aspergillus fumigatus. Indifference was the only type of
      interaction observed in vitro. Anidulafungin at 1 and 5 mg/kg of body weight/day,
      amphotericin B at 1 mg/kg/day, and combination therapy prolonged the survival of
      mice with invasive aspergillosis. Anidulafungin at 5 mg/kg/day, alone and in
      combination with amphotericin B, reduced the kidney fungal burden. Overall, the
      combination was not superior to the most active single drug.

PMID- 19596891
TI  - The diarylquinoline R207910 is bactericidal against Mycobacterium leprae in mice
      at low dose and administered intermittently.
AB  - The diarylquinoline R207910 is profoundly bactericidal in a murine model of
      tuberculosis. Previously, R207910 was also found to be bactericidal for
      Mycobacterium leprae-infected mice during lag phase. Herein we evaluate the
      bactericidal efficacy of R207910 (1 to 120 mg/kg of body weight) when
      administered five times weekly, once weekly, and once monthly during logarithmic
      multiplication of M. leprae organisms. All treatments were found to be
      bactericidal, suggesting that both low and intermittent dosing with R207910 holds
      promise for leprosy patients.

PMID- 19596893
TI  - Effects of probiotics and commensals on intestinal epithelial physiology:
      implications for nutrient handling.
AB  - Eukaryotes and prokaryotes have developed mutually beneficial relationships over
      millennia of evolutionary adaptation. Bacteria in our gut rely on our diet and
      the protected environment of our bodies just as our health depends on byproducts
      of microbial metabolism. Microorganisms of the gut microbiota ferment
      carbohydrates into short-chain fatty acids, convert dietary and endogenous
      nitrogenous compounds into ammonia and microbial protein, and synthesize and
      activate B vitamins and vitamin K. The benefit from their activity is multiplex
      and translates into increased energy for the gut epithelial cells, balanced
      absorption of salt and water, nitrogen recycling, breakdown of complex lipids and
      cholesterol, and detoxification of waste compounds.

PMID- 19596892
TI  - Pyramidal cells of rodent presubiculum express a tetrodotoxin-insensitive Na+
      current.
AB  - Presubicular neurons are activated physiologically by a specific preferred head
      direction. Here we show that firing in these neurones is characterized by action
      potentials with a large overshoot and a reduced firing frequency adaptation
      during repetitive firing. We found that a component of the sodium current of
      presubicular cells was not abolished by tetrodotoxin (TTX, 10 mum) and was
      activated at more depolarized voltages than TTX-sensitive currents. This inward
      current was completely abolished by the removal of external sodium, suggesting
      that sodium is the charge carrier of this TTX-insensitive (TTX-I) current. The
      channels responsible for the TTX-I sodium current seemed to be expressed at sites
      distant from the soma, giving rise to a voltage-dependent delay in current
      activation. The voltage required for half-maximal activation was 21 mV, and 36 mV
      for inactivation, which is similar to that reported for Na(V)1.8 sodium channels.
      However, the kinetics were considerably slower, with a time constant of current
      decay of 1.4 s. The current was not abolished in pyramidal cells from animals
      lacking either the Na(V)1.8 or the Na(V)1.9 subunit. This, possibly novel, TTX-I
      sodium current could contribute to the coding functions of presubicular neurons,
      specifically the maintained firing associated with signalling of a stable head
      position.

PMID- 19596895
TI  - Substrate interactions of the electroneutral Na+-coupled inorganic phosphate
      cotransporter (NaPi-IIc).
AB  - The SLC34 solute carrier family comprises the electrogenic NaPi-IIa/b and the
      electroneutral NaPi-IIc, which display Na(+) : P(i) cotransport stoichiometries
      of 3 : 1 and 2 : 1, respectively. We previously proposed that NaPi-IIc lacks one
      of the three Na(+) interaction sites hypothesised for the electrogenic isoforms,
      but, unlike NaPi-IIa/b, its substrate binding order is undetermined. By
      expressing NaPi-IIc in Xenopus oocytes, isotope influx and efflux assays gave
      results consistent with Na(+) being the first and last substrate to bind. To
      further investigate substrate interactions, we applied a fluorometry-based
      technique that uses site-specific labelling with a fluorophore to characterize
      substrate-induced conformational changes. A novel Cys was introduced in the third
      extracellular loop of NaPi-IIc that could be labelled with a reporter fluorophore
      (MTS-TAMRA). Although labelling resulted in suppression of cotransport as
      previously reported for the electrogenic isoforms, changes in fluorescence were
      induced by changes in extracellular Na(+) concentration in the absence of P(i)
      and by changes in extracellular P(i) concentration in presence of Na(+). These
      data, combined with (32)P uptake data, also support a binding scheme in which
      Na(+) is the first substrate to interact. Moreover, the apparent P(i) affinity
      from fluorometry agreed with that from (32)P uptake, confirming the applicability
      of the fluorometric technique for kinetic studies of electroneutral carriers.
      Analysis of the fluorescence data showed that like the electrogenic NaPi-IIb, 2
      Na(+) ions interact cooperatively with NaPi-IIc before P(i) binding, which
      implies that only one of these is translocated. This result provides compelling
      evidence that SLC34 proteins share common motifs for substrate interaction and
      that cotransport and substrate binding stoichiometries are not necessarily
      equivalent.

PMID- 19596896
TI  - Energy turnover in relation to slowing of contractile properties during fatiguing
      contractions of the human anterior tibialis muscle.
AB  - Slowing and loss of muscle power are major factors limiting physical performance
      but little is known about the molecular mechanisms involved. The slowing might be
      a consequence of slow detachment of cross bridges and, if this were the case,
      then a reduction in the ATP cost of an isometric contraction would be expected as
      the muscle fatigued. The human anterior tibialis muscle was stimulated repeatedly
      under ischaemic conditions at 50 Hz for 1.6 s with a 50% duty cycle and muscle
      metabolites measured by (31)P magnetic resonance spectroscopy. Over the course of
      20 contractions the half-time of relaxation increased from 36.5 +/- 0.09 ms (mean
      +/- s.e.m.) to 113 +/- 17 ms and isometric force was reduced to 63 +/- 3% of the
      initial value. ATP turnover was determined from the change in high energy
      phosphates and lactate production, the latter estimated from the change of
      intracellular pH. ATP turnover over the first three contractions was 2.45 +/-
      0.09 mM s(1) and decreased to 1.8 +/- 0.06 mm s(1) over the last five tetani.
      However, when this latter value was normalised for the decrease in isometric
      force, it became 2.56 +/- 0.3 mM s(1), which is the same as the turnover of the
      fresh muscle. The data suggest that the rate of cross bridge detachment is
      unaffected by fatigue and are consistent the suggestion that it is the rate of
      attachment which is slowed rather than the rate of detachment. The present
      results focus attention on stages in the cross bridge cycle concerned with
      attachment and the transition from low to high force states that may be
      influenced by metabolic changes in the fatiguing muscle.

PMID- 19596897
TI  - Biaxial strain and variable stiffness in aponeuroses.
AB  - The elastic structures of many muscles include both an extramuscular free tendon
      as well as a sheet-like aponeurosis. An important distinguishing feature of
      aponeuroses is that these tendinous structures function as the attachment and
      insertion surfaces of muscle fascicles and therefore surround a substantial
      portion of the muscle belly. As a result, aponeuroses must expand both parallel
      (longitudinal) and perpendicular (transverse) to a muscle's line of action when
      contracting muscles bulge to maintain a constant volume. In this study, we use
      biplanar high-speed fluoroscopy to track the strain patterns of the turkey
      lateral gastrocnemius aponeurosis during active and passive force production in
      situ. We find that the behaviour of the aponeurosis during passive force
      production is consistent with uniaxial loading, as aponeuroses stretch only in
      the longitudinal direction. By contrast, our results show that aponeuroses are
      stretched in both longitudinal and transverse directions during active force
      production and that transverse strains are on average 4 times greater than
      longitudinal strains. Biaxial loading of aponeuroses appears to effectively
      modulate longitudinal stiffness, as we find the measured stiffness in the
      longitudinal direction varies in proportion to transverse strain. We conclude
      that biaxial strain during active force production distinguishes aponeuroses from
      free tendons and may function to dynamically modulate stiffness along the axis of
      muscle force production. It is likely that consideration of strains measured only
      in the longitudinal direction result in an underestimation of aponeurosis
      stiffness as well as its capacity for elastic energy storage.

PMID- 19596898
TI  - Multiple signalling pathways redundantly control glucose transporter GLUT4 gene
      transcription in skeletal muscle.
AB  - Increased glucose transporter GLUT4 expression in skeletal muscle is an important
      benefit of regular exercise, resulting in improved insulin sensitivity and
      glucose tolerance. The Ca(2+)-calmodulin-dependent kinase II (CaMKII),
      calcineurin and AMPK pathways have been implicated in GLUT4 gene regulation based
      on pharmacological evidence. Here, we have used a more specific genetic approach
      to establish the relative role of the three pathways in fast and slow muscles.
      Plasmids coding for protein inhibitors of CaMKII or calcineurin were co
      transfected in vivo with a GLUT4 enhancer-reporter construct either in normal
      mice or in mice expressing a kinase dead (KD) AMPK mutant. GLUT4 reporter
      activity was not inhibited in the slow soleus muscle by blocking either CaMKII or
      calcineurin alone, but was inhibited by blocking both pathways. GLUT4 reporter
      activity was likewise unchanged in the soleus of KD-AMPK mice, but was
      significantly reduced by incapacitation of either CaMKII or calcineurin in these
      mice. On the other hand, in the fast tibialis anterior (TA) muscle, calcineurin
      appears to exert a prominent role in the control of GLUT4 reporter activity,
      independent of CaMKII and AMPK. The results point to a muscle type-specific and
      redundant regulation of GLUT4 enhancer based on the interplay of multiple
      signalling pathways, all of which are known to affect myocyte enhancing factor 2
      (MEF2) transcriptional activity, a point of convergence of different pathways on
      muscle gene regulation.

PMID- 19596899
TI  - Influenza virus M2 protein inhibits epithelial sodium channels by increasing
      reactive oxygen species.
AB  - The mechanisms by which replicating influenza viruses decrease the expression and
      function of amiloride-sensitive epithelial sodium channels (ENaCs) have not been
      elucidated. We show that expression of M2, a transmembrane influenza protein,
      decreases ENaC membrane levels and amiloride-sensitive currents in both Xenopus
      oocytes, injected with human alpha-, beta-, and gamma-ENaCs, and human airway
      cells (H441 and A549), which express native ENaCs. Deletion of a 10-aa region
      within the M2 C terminus prevented 70% of this effect. The M2 ENaC down
      regulation occurred at normal pH and was prevented by MG-132, a proteasome and
      lysosome inhibitor. M2 had no effect on Liddle ENaCs, which have decreased
      affinity for Nedd4-2. H441 and A549 cells transfected with M2 showed higher
      levels of reactive oxygen species, as shown by the activation of redox-sensitive
      dyes. Pretreatment with glutathione ester, which increases intracellular reduced
      thiol concentrations, or protein kinase C (PKC) inhibitors prevented the
      deleterious effects of M2 on ENaCs. The data suggest that M2 protein increases
      steady-state concentrations of reactive oxygen intermediates that simulate PKC
      and decrease ENaCs by enhancing endocytosis and its subsequent destruction by the
      proteasome. These novel findings suggest a mechanism for the influenza-induced
      rhinorrhea and life-threatening alveolar edema in humans.

PMID- 19596900
TI  - Transcription independent insulation at TFIIIC-dependent insulators.
AB  - Chromatin insulators separate active from repressed chromatin domains. In yeast
      the RNA pol III transcription machinery bound to tRNA genes function with histone
      acetylases and chromatin remodelers to restrict the spread of heterochromatin.
      Our results collectively demonstrate that binding of TFIIIC is necessary for
      insulation but binding of TFIIIB along with TFIIIC likely improves the
      probability of complex formation at an insulator. Insulation by this
      transcription factor occurs in the absence of RNA polymerase III or polymerase II
      but requires specific histone acetylases and chromatin remodelers. This analysis
      identifies a minimal set of factors required for insulation.

PMID- 19596901
TI  - METT-10, a putative methyltransferase, inhibits germ cell proliferative fate in
      Caenorhabditis elegans.
AB  - Germ-line stem cells are unique because they either self-renew through mitosis
      or, at a certain frequency, switch to meiosis and produce gametes. The switch
      from proliferation to meiosis is tightly regulated, and aberrations in switching
      result in either too little or too much proliferation. To understand the genetic
      basis of this regulation, we characterized loss-of-function mutations and a novel
      tumorous allele of Caenorhabditis elegans mett-10, which encodes a conserved
      putative methyltransferase. We show that METT-10 is a nuclear protein that acts
      in the germ line to inhibit the specification of germ-cell proliferative fate.
      METT-10 also promotes vulva, somatic gonad, and embryo development and ensures
      meiotic development of those germ cells that do differentiate. In addition,
      phenotypic analysis of a mett-10 null allele reveals that METT-10 enables mitotic
      cell cycle progression. The finding that METT-10 functions to inhibit germ-cell
      proliferative fate, despite promoting mitotic cell cycle progression of those
      germ cells that do proliferate, separates the specification of proliferative fate
      from its execution.

PMID- 19596902
TI  - The action of purifying selection, mutation and drift on fitness epistatic
      systems.
AB  - For different fitness mutational models, with epistasis introduced, we simulated
      the consequences of drift (D scenario) or mutation, selection, and drift (MSD
      scenario) in populations at the MSD balance subsequently subjected to bottlenecks
      of size N = 2, 10, 50 during 100 generations. No "conversion" of nonadditive into
      additive variance was observed, all components of the fitness genetic variance
      initially increasing with the inbreeding coefficient F and subsequently
      decreasing to zero (D) or to an equilibrium value (MSD). In the D scenario,
      epistasis had no appreciable effect on inbreeding depression and that on the
      temporal change of variance components was relevant only for high rates of strong
      epistatic mutation. In parallel, between-line differentiation in mean fitness
      accelerated with F and that in additive variance reached a maximum at F
      approximately 0.6-0.7, both processes being intensified by strong epistasis. In
      the MSD scenario, however, the increase in additive variance was smaller, as it
      was used by selection to purge inbreeding depression (N > or = 10), and selection
      prevented between-line differentiation. Epistasis, either synergistic or
      antagonistic (this leading to multiple adaptive peaks), had no appreciable effect
      on MSD results nor, therefore, on the evolutionary rate of fitness change.

PMID- 19596904
TI  - Temperature-sensitive mutations made easy: generating conditional mutations by
      using temperature-sensitive inteins that function within different temperature
      ranges.
AB  - Reversible and easy to use, temperature-sensitive (TS) mutations are powerful
      tools for studying gene function. However, TS alleles are rare and difficult to
      generate and identify, and this has limited their use in most multicellular
      organisms. We have generated and characterized 41 intein switches, temperature
      sensitive Sce VMA mutations that splice only at the permissive temperatures to
      generate intact host proteins. At nonpermissive temperatures, they fail to
      splice, resulting in a loss of function of the proteins in which they reside. By
      inserting an intein switch into a protein of interest, one can turn on and off
      the activities of the engineered protein with a simple temperature shift. The 41
      TS inteins function in five different temperature ranges, with permissive
      temperatures ranging from 18 degrees to 30 degrees . This collection makes it
      possible to choose a TS-intein switch according to the optimal growth temperature
      of an organism or to suit a special experimental design.

PMID- 19596903
TI  - Conservation of domain structure in a fast-evolving heterochromatic SUUR protein
      in drosophilids.
AB  - Different genomic regions replicate at a distinct time during S-phase. The SuUR
      mutation alters replication timing and the polytenization level of intercalary
      and pericentric heterochromatin in Drosophila melanogaster salivary gland
      polytene chromosomes. We analyzed SuUR in different insects, identified conserved
      regions in the protein, substituted conserved amino acid residues, and studied
      effects of the mutations on SUUR function. SuUR orthologs were identified in all
      sequenced drosophilids, and a highly divergent ortholog was found in the mosquito
      genome. We demonstrated that SUUR evolves at very high rate comparable with that
      of Transformer. Remarkably, upstream ORF within 5' UTR of the gene is more
      conserved than SUUR in drosophilids, but it is absent in the mosquito. The domain
      structure and charge of SUUR are maintained in drosophilids despite the high
      divergence of the proteins. The N-terminal part of SUUR with similarity to the
      SNF2/SWI2 proteins displays the highest level of conservation. Mutation of two
      conserved amino acid residues in this region impairs binding of SUUR to polytene
      chromosomes and reduces the ability of the protein to cause DNA underreplication.
      The least conserved middle part of SUUR interacting with HP1 retains positively
      and negatively charged clusters and nuclear localization signals. The C terminus
      contains interlacing conserved and variable motifs. Our results suggest that SUUR
      domains evolve with different rates and patterns but maintain their features.

PMID- 19596905
TI  - C-terminal flap endonuclease (rad27) mutations: lethal interactions with a DNA
      ligase I mutation (cdc9-p) and suppression by proliferating cell nuclear antigen
      (POL30) in Saccharomyces cerevisiae.
AB  - During lagging-strand DNA replication in eukaryotic cells primers are removed
      from Okazaki fragments by the flap endonuclease and DNA ligase I joins nascent
      fragments. Both enzymes are brought to the replication fork by the sliding clamp
      proliferating cell nuclear antigen (PCNA). To understand the relationship among
      these three components, we have carried out a synthetic lethal screen with cdc9
      p, a DNA ligase mutation with two substitutions (F43A/F44A) in its PCNA
      interaction domain. We recovered the flap endonuclease mutation rad27-K325* with
      a stop codon at residue 325. We created two additional rad27 alleles, rad27-A358*
      with a stop codon at residue 358 and rad27-pX8 with substitutions of all eight
      residues of the PCNA interaction domain. rad27-pX8 is temperature lethal and
      rad27-A358* grows slowly in combination with cdc9-p. Tests of mutation avoidance,
      DNA repair, and compatibility with DNA repair mutations showed that rad27-K325*
      confers severe phenotypes similar to rad27Delta, rad27-A358* confers mild
      phenotypes, and rad27-pX8 confers phenotypes intermediate between the other two
      alleles. High-copy expression of POL30 (PCNA) suppresses the canavanine mutation
      rate of all the rad27 alleles, including rad27Delta. These studies show the
      importance of the C terminus of the flap endonuclease in DNA replication and
      repair and, by virtue of the initial screen, show that this portion of the enzyme
      helps coordinate the entry of DNA ligase during Okazaki fragment maturation.

PMID- 19596906
TI  - Multilocus patterns of nucleotide diversity and divergence reveal positive
      selection at candidate genes related to cold hardiness in coastal Douglas Fir
      (Pseudotsuga menziesii var. menziesii).
AB  - Forest trees exhibit remarkable adaptations to their environments. The genetic
      basis for phenotypic adaptation to climatic gradients has been established
      through a long history of common garden, provenance, and genecological studies.
      The identities of genes underlying these traits, however, have remained elusive
      and thus so have the patterns of adaptive molecular diversity in forest tree
      genomes. Here, we report an analysis of diversity and divergence for a set of 121
      cold-hardiness candidate genes in coastal Douglas fir (Pseudotsuga menziesii var.
      menziesii). Application of several different tests for neutrality, including
      those that incorporated demographic models, revealed signatures of selection
      consistent with selective sweeps at three to eight loci, depending upon the
      severity of a bottleneck event and the method used to detect selection. Given the
      high levels of recombination, these candidate genes are likely to be closely
      linked to the target of selection if not the genes themselves. Putative homologs
      in Arabidopsis act primarily to stabilize the plasma membrane and protect against
      denaturation of proteins at freezing temperatures. These results indicate that
      surveys of nucleotide diversity and divergence, when framed within the context of
      further association mapping experiments, will come full circle with respect to
      their utility in the dissection of complex phenotypic traits into their genetic
      components.

PMID- 19596909
TI  - Efficacy of dietary antioxidants combined with a chemotherapeutic agent on human
      colon cancer progression in a fluorescent orthotopic mouse model.
AB  - We report here the efficacy of dietary antioxidants in combination with
      chemotherapy on tumor growth in the orthotopic COLO-205-green fluorescent protein
      (GFP) human colon cancer mouse model. The orthotopically-transplanted nude mice
      used for the study were randomly divided into 5 groups (A-E) after surgical
      orthotopic implantation (SOI) of tumor tissue. The following diets were given:
      Diet A, modified AIN-93M mature rodent diet with 4% fish oil; Diet B, modified
      AIN-93M which contains added antioxidants vitamin A, vitamin E, and selenium at
      levels present in the standard AIN-93M diet; Diet C, Diet A without added
      antioxidants vitamin A, vitamin E, or selenium; Diet D, Diet A with 5 times the
      amount of added antioxidants vitamin A, vitamin E, and selenium present in Diet
      B. Cisplatin, 7 mg/kg, was administered intraperitoneally on day 16 after SOI.
      Throughout the course of treatment, noninvasive whole-body imaging, based on the
      GFP expression of the tumor, permitted visualization of tumor progression. At
      sacrifice, the mean tumor weights showed significant statistical differences in
      all of the treated groups compared to the negative control (no cisplatin
      treatment) (p <or=0.001). The mean tumor weight showed a significant statistical
      difference between the Diet D combined with the cisplatin group compared to Diet
      B combined with cisplatin (p=0.038). Thus, we have demonstrated that Diet D is
      effective against tumor growth in combination with cisplatin in the fluorescent
      mouse model of colon cancer COLO-205 GFP. The results of the present study
      therefore indicate enhancement of cisplatin efficacy by high-dose antioxidants in
      combination with fish oil for colon cancer progression and suggests the design of
      clinical trials for this regimen.

PMID- 19596907
TI  - Collaboration between the essential Esa1 acetyltransferase and the Rpd3
      deacetylase is mediated by H4K12 histone acetylation in Saccharomyces cerevisiae.
AB  - Histone modifications that regulate chromatin-dependent processes are catalyzed
      by multisubunit complexes. These can function in both targeting activities to
      specific genes and in regulating genomewide levels of modifications. In
      Saccharomyces cerevisiae, Esa1 and Rpd3 have opposing enzymatic activities and
      are catalytic subunits of multiple chromatin modifying complexes with key roles
      in processes such as transcriptional regulation and DNA repair. Esa1 is an
      essential histone acetyltransferase that belongs to the highly conserved MYST
      family. This study presents evidence that the yeast histone deacetylase gene,
      RPD3, when deleted, suppressed esa1 conditional mutant phenotypes. Deletion of
      RPD3 reversed rDNA and telomeric silencing defects and restored global H4
      acetylation levels, in addition to rescuing the growth defect of a temperature
      sensitive esa1 mutant. This functional genetic interaction between ESA1 and RPD3
      was mediated through the Rpd3L complex. The suppression of esa1's growth defect
      by disruption of Rpd3L was dependent on lysine 12 of histone H4. We propose a
      model whereby Esa1 and Rpd3L act coordinately to control the acetylation of H4
      lysine 12 to regulate transcription, thereby emphasizing the importance of
      dynamic acetylation and deacetylation of this particular histone residue in
      maintaining cell viability.

PMID- 19596908
TI  - Epistatic effects of the protease/chaperone HflB on some damaged forms of the
      Escherichia coli ammonium channel AmtB.
AB  - The Escherichia coli ammonium channel AmtB is a trimer in which each monomer
      carries a pore for substrate conduction and a cytoplasmic C-terminal extension of
      approximately 25 residues. Deletion of the entire extension leaves the protein
      with intermediate activity, but some smaller lesions in this region completely
      inactivate AmtB, as do some lesions in its cytoplasmic loops. We here provide
      genetic evidence that inactivation depends on the essential protease HflB, which
      appears to cause inactivation not as a protease but as a chaperone. Selection for
      restored function of AmtB is a positive selection for loss of the
      ATPase/chaperone activity of HflB and reveals that the conditional lethal
      phenotype for hflB is cold sensitivity. Deletion of only a few residues from the
      C terminus of damaged AmtB proteins seems to prevent HflB from acting on them.
      Either yields the intermediate activity of a complete C-terminal deletion. HflB
      apparently "tacks" damaged AmtB tails to the adjacent monomers. Knowing that HflB
      has intervened is prerequisite to determining the functional basis for AmtB
      inactivation.

PMID- 19596910
TI  - N-terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava
      F7(776-788)], aid differentiation of E75-TCR+CD8+ cells to perforin-positive
      cells.
AB  - The objective of this study was to discover whether the peptides LRMK and LRMK
      Ava linked to the N-terminus of peptides HER-2 (774-788) and HER-2 (776-788),
      respectively, help differentiation of E75-TCR(+)CD8(+) cells. Activation was
      quantified in terms of proliferation of E75-TCR(+)CD8(+) cells expressing high,
      medium and low density amounts of the specific TCR. Differentiation to functional
      CD8(+) cells was quantified as induction of Perforin (Perf), the lytic-enzyme
      which mediates the effector function of CD8(+) cells, in E75-TCR(+)CD8(+) cells.
      Peripheral blood mononuclear cells (PBMCs) of 3 patients activated with E75(+)AE
      37 and E75(+)AE-47 more greatly increased the number of E75-TCR(Hi) CD8(+)Perf(+)
      cells than PBMCs activated by AE-47 alone or AE-47(+) E75. E75 plus cytokines and
      cytokines alone activated more E75-TCR(Low) cells than did AE-37 and AE-47.
      E75(+) AE-37 and AE-37 also induced differentiation of small- and medium-size
      activated CD8(+) cells from BRC ascites, in allogeneic activation, to Perf(+)
      cells. Preferential differentiation of E75-TCR(+)CD8(+)Perf(+) cells in distinct
      patients by AE-37 and AE-47 indicates that cancer vaccines will benefit from such
      correct individual and disease-associated help. Additional studies using the
      natural peptides p776 and F7 are needed to understand whether the LRMK-(Ava)
      tetra-, or pentamer augments or inhibits differentiation of CD8(+) cells,
      compared with native, natural HER-2 peptides and/or protects CD8(+) cells
      activated by E75 and by other HLA-I bound peptides from death. Our findings also
      develop a model for uniform quantification of differentiated CD8(+) effectors.

PMID- 19596911
TI  - Anaplastic thyroid carcinoma exhibits intratumoral molecular homogeneity for a
      therapeutic target panel.
AB  - BACKGROUND: The objective of this work was to determine if molecular
      heterogeneity exists between different intratumoral histological subtype foci of
      anaplastic thyroid carcinoma (ATC). MATERIALS AND METHODS: A tissue microarray
      composed of 12 ATC specimens from 6 patients (two discrete histological subtype
      foci from each tumor) were evaluated for expression of 51 different molecular
      markers. Significant associations between marker staining and tumor focus
      (primary versus secondary) or subtype (epithelioid, giant cell, or spindled) were
      determined using contingency table statistics and samples and markers were
      clustered using a hierarchical clustering algorithm. Correlation between marker
      staining for the two tumor foci was also evaluated for each patient using a
      Spearman correlation. RESULTS: Significant correlations and clustering were
      observed for the overall staining patterns for paired anaplastic foci from the
      same patient. This suggests that the different intratumoral foci showed
      consistent or homogeneous staining. CONCLUSION: These results suggest that
      observed ATC phenotypic heterogeneity does not necessarily reflect heterogeneity
      for therapeutic target expression.

PMID- 19596912
TI  - The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast
      cancer.
AB  - BACKGROUND: The aim of the study was to assess the prognostic role of CD4 and CD8
      expression and the type, density, localization and distribution of tumor
      infiltrating lymphocytes (TILs) in patients with breast cancer. MATERIALS AND
      METHODS: Tissue samples were obtained from 88 breast cancer patients with
      operable disease and ductal histology. Forty-three women had pathologically
      confirmed axillary lymph node involvement. The TILs and expression of CD8
      (cytotoxic T-cells) and CD4 (T-helper cells) were evaluated in the tumor samples
      using mouse monoclonal antibodies. RESULTS: Thirteen patients relapsed; nine of
      them had strong expression of CD4 and CD8, which was statistically significant.
      The patients with high expression of CD4 or CD8 had distinctly worse cancer
      specific overall survival (OS). High correlations between CD4 and CD8 expression
      and lymph node status and intensity of lymphatic infiltrate as well as between
      both markers were found. CONCLUSION: The analysis of tumor-infiltrating immune
      cells may be a valuable prognostic tool and a marker of lymph node involvement.

PMID- 19596913
TI  - FEN1 is overexpressed in testis, lung and brain tumors.
AB  - Flap endonuclease 1 (FEN1) is a DNA replication/repair protein involved in
      Okazaki fragment processing, long-patch base excision repair, DNA double-strand
      break repair and stalled replication fork restart. FEN1 is also important for
      preservation of telomere stability and thus a key node in maintaining genomic
      stability. The aim of the present study was to elucidate the level of expression
      of FEN1 protein in cancer of testis, lung and brain. FEN1 protein expression was
      studied by Western blot analysis in specimens of tumor tissues compared with the
      normal tissue from the same patient or normal brain extract. In addition, FEN1
      was transiently down-regulated in the glioblastoma cell line LN308 by
      transfection with siRNA. The transfected cells were treated with cisplatin,
      temozolomide, nimustine and methyl methanesulfonate (MMS). Induced apoptosis
      (subG1 fraction) was analysed by flow cytometry. Our data show a clear
      overexpression of FEN1 in 19/25 samples from testicular tumors (mostly seminomas)
      and 4/4 samples from lung tumors (non-small cell lung cancer). For brain tumors,
      9/11 glioblastoma multiforme and 5/8 astrocytomas expressed FEN1 protein at a
      higher level than did normal brain tissue. Overall, the data demonstrate that
      FEN1 overexpression is common in testis, lung and brain tumors. Low-level
      expression of FEN1 by siRNA down-regulation increased sensitivity to methylating
      agents (temozolomide, MMS) and cisplatin in LN308 glioma cells, which indicates
      that altered FEN1 expression might impact the therapeutic response.

PMID- 19596914
TI  - Immunobiological and experimental aspects of malignant astrocytoma.
AB  - Today several findings indicate that a multifactorial strategy is the best
      strategy for treating cancer. Although radiotherapy, chemotherapy and surgery
      have been differently applied to treat human gliomas, no substantial improvement
      in life expectancy has been observed. Starting from 1992, the goal of our studies
      was to obtain new biological data on malignant astrocytomas to better understand
      the basic biology of the tumour and these are reviewed here. Immunotherapy may
      represent an available method in addition to the traditional therapeutic
      approaches. Starting from 1991, we set up a cellular model of lymphocytes
      obtained from peripheral blood of healthy patients treated with interleukin-2 (IL
      2) in order to study the role of IL-2 in regulating lymphocytes activation. The
      lymphocytes responding to IL-2 treatment, named lymphokine-activated killer (LAK)
      cells, have a killer non MHC restricted activity, and are able to kill autologous
      and allogenic glioma cells. The interaction of LAK cells with various normal and
      transformed targets indicates that LAK cells recognize surface structures present
      both on normal and transformed cells. However, only the interaction with
      transformed cells induces lytic events and LAK cells can act as "surgical
      weapons" against tumour cells independently from their cell cycle. Much recent
      effort has focused on identifying the immune escape mechanisms used by glioma
      cells, in particular the modulation of the human leukocyte antigen (HLA) and
      antigen processing machinery component expression. Finally, another interesting
      field of research that will be presented is that of new tumour biomarkers of
      proliferation and apoptosis, cytokine/chemokine release and cytokine/chemokine
      receptors.

PMID- 19596915
TI  - Expression of JNK-interacting protein JIP-1 and insulin-like growth factor II in
      Wilms tumour cell lines and primary Wilms tumours.
AB  - JNK-interacting protein 1 (JIP-1) is an important scaffolding protein in the JNK
      signalling pathway. It is also believed to play a role in the mediation of
      mitogenic messages from the plasma membrane to the cell interior. Previous
      studies suggest that the JIP-gene is co-regulated with the insulin-like growth
      factor II (IGF II) gene, thereby contributing to the growth stimulatory effects
      of this potent growth factor. The striking coexpression of these two genes was
      found in murine fetuses as well as in primary human embryonic tumours. When six
      primary Wilms tumours were examined, the two genes showed a high degree of co
      variation in the sense that high expression of IGF II was followed by high
      expression of JIP-1 and vice versa. However, when the human Wilms tumour cell
      line WCCS-1 was examined, a very modest intrinsic expression of IGF II was
      accompanied by a moderate expression of JIP-1. When exogenous IGF II was added,
      which has previously been shown to induce apoptosis in this cell line, the JIP-1
      expression increased. These data suggest that JIP-1 has a more complex role in
      the regulation of proliferation as well as programmed cell death.

PMID- 19596917
TI  - MYC insertions in diffuse-type gastric adenocarcinoma.
AB  - BACKGROUND: MYC is important in gastric carcinogenesis. A few studies reported
      MYC translocation or insertion associated with gastric cancer. MATERIALS AND
      METHODS: MYC copy number and its insertion, as well as the chromosomes in which
      MYC was inserted, were evaluated by fluorescence in situ hybridization assay in
      interphase and metaphase cells of 12 diffuse-type gastric cancer samples. MYC
      protein expression was evaluated by immunohistochemistry. RESULTS: The presence
      of 3 MYC signals was the most frequent alteration. All cases also presented 4 and
      5 MYC signals. In all samples, we observed chromosome 8 trisomy with MYC copies
      and MYC insertion into the chromosomes 2, 7, 14, 17, 18 and 22. All samples
      presented nucleic and cytoplasmic immunoreactivity. CONCLUSION: MYC cytoplasmic
      immunoreactivity can be the result of MYC insertion with the breakpoints within
      or close to the regions that are able to target the nucleus. MYC insertion and
      cytoplasmatic immunoreactivity may be a common characteristic of diffuse-type
      gastric cancer.

PMID- 19596916
TI  - Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer
      cells.
AB  - BACKGROUND: Toll-like receptors (TLRs) are involved in innate immunity.
      Overexpression of TLRs has been implicated in various types of cancer including
      colorectal cancer (CRC). The phosphatidylinositol-3'-kinase (PI3K)/Akt signaling
      pathway is involved in CRC growth and progression. In this study, we determined
      whether TLR4 signaling and PI3K/Akt pathway activation occur in CRCs. MATERIALS
      AND METHODS: Human CRCs and adjacent mucosa were evaluated for TLR4 expression.
      CRC cell lines were treated with lipopolysaccharide (LPS), endogenous TLR4
      ligand, to assess Akt phosphorylation. RESULTS: Human CRCs overexpressed TLR4
      compared to matched normal mucosa. Additionally, TLR4 was expressed in CRC cells
      and LPS treatment increased Akt phosphorylation of TLR4-positive CRCs in a time
      dependent manner. CONCLUSION: Our results identify TLR4 expression in human CRCs
      and activation of PI3K with LPS treatment. These findings suggest possible
      treatment strategies targeting TLR4 in CRC.

PMID- 19596918
TI  - Panaxanthone isolated from pericarp of Garcinia mangostana L. suppresses tumor
      growth and metastasis of a mouse model of mammary cancer.
AB  - BACKGROUND: The antitumor growth and antimetastatic activity of panaxanthone
      (approximately 80% alpha-mangostin and 20% gamma-mangostin) were studied in a
      mouse metastatic mammary cancer model that produces a metastatic spectrum similar
      to that seen in human breast cancer. MATERIALS AND METHODS: Mammary tumors,
      induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were
      subsequently treated with panaxanthone at 0, 2,500, or 5,000 ppm in their diet.
      In vitro studies were also conducted to evaluate the effects of alpha-mangostin,
      the main component of panaxanthone, on BJMC3879 cells. RESULTS: In the in vivo
      study, tumor volumes were significantly suppressed in mice treated with 2,500 and
      5,000 ppm panaxanthone in their diet. The multiplicity of lung metastasis was
      significantly lower in the 5,000 ppm group. Lymph node metastasis also tended to
      decrease in the 5,000 ppm group but not significantly. The antitumor effects of
      panaxanthone were associated with elevation of apoptotic cell death,
      antiproliferation (inhibition of PCNA) and antiangiogenesis (inhibition of
      microvessel density). The in vitro study demonstrated that alpha-mangostin
      induced apoptosis, as evidenced by increased numbers of TUNEL-positive cells,
      elevated activities of caspases and a decrease in mitochondrial membrane
      potential, cell cycle arrest in the G(1)-phase and decreases in the cell
      population in the S- and G(2)/M-phases. CONCLUSION: These results suggest that
      the observed antimetastatic activity of panaxanthone may be of clinical
      significance as adjuvant therapy in metastatic human breast cancer, and may also
      be useful as a chemopreventative of breast cancer development.

PMID- 19596919
TI  - Conversion of prostate cancer from hormone independency to dependency due to
      AMACR inhibition: involvement of increased AR expression and decreased IGF1
      expression.
AB  - Androgen-independent prostate cancer eventually develops metastasis, and radical
      treatment may not be possible for patients at this stage. In this study, we
      examined the gene-expression profiles of two prostate cancer cell lines, LNCaP
      (androgen-dependent) and C4-2 (androgen-independent), using cDNA-microarray
      hybridization. We focused on the expression of alpha-methylacyl-CoA racemase
      (AMACR), whose expression is much higher in C4-2 than in LNCaP, and investigated
      its biological role in acquisition of androgen-independent cancer growth.
      Immunohistochemistry and Western blot analysis of subcellular fractions revealed
      that AMACR expression was much stronger in C4-2 than in LNCaP. Inhibition of
      AMACR expression using AMACR-siRNA induced an increase in the expression of
      androgen receptor (AR) and B-cell translocation gene 1, along with a decrease in
      the expression of genes associated with cancer progression, including insulin
      like growth factor I and platelet-derived growth factor alpha, in C4-2 with
      compared to non-treated C4-2. BrdU analysis and MTT assay demonstrated that AMACR
      inhibition induced a significant decrease of cell viability in C4-2 when cultured
      in androgen-depleted serum, becoming consistent with that of LNCaP, suggesting
      that AMACR inhibition may induce an increase in the expression of AR and
      characteristic conversion of prostate cancer cells from hormone independency to
      hormone dependency. We suggest that AMACR inhibition may be a new strategy for
      treatment of patients with hormone-refractory prostate cancer.

PMID- 19596920
TI  - Doxorubicin and congo red effectiveness on prion infectivity in golden Syrian
      hamster.
AB  - The effect of doxorubicin and Congo Red on prion protein (PrP) infectivity in
      experimental scrapie was studied to better understand the effect of these
      compounds in prion diseases and to establish whether a dose-response correlation
      exists for Congo Red. This was performed in order to test the effectiveness of
      compounds that may easily be used in human prion diseases. Brain homogenate
      containing membrane bound PrPSc monomers was used as inoculum and was previously
      incubated with doxorubicin 10(-3) M and with increasing concentrations of Congo
      Red ranging from 10(-7) to 10(-2) M. This study shows for the first time that
      doxorubicin, and confirms that Congo Red, may interact with pathological PrP
      monomers modifying their infectious properties. Pre-incubation of infected brain
      homogenate with Congo Red resulted in prolonged incubation time and survival,
      independently of Congo Red concentration (p<0.05). Doxorubicin and Congo Red
      effects do not depend upon interaction with PrP amyloid material.

PMID- 19596921
TI  - Expression of MMP-7, MMP-9, TIMP-1 and TIMP-2 mRNA in lung tissue of patients
      with non-small cell lung cancer (NSCLC) and benign pulmonary disease.
AB  - The expression of matrix metallo-proteinases (MMP-7 and MMP-9) and tissue
      inhibitors of metalloproteinases (TIMP-1 and TIMP-2), which are involved in the
      degradation of the extracellular matrix (ECM) and tumor growth, was investigated
      in normal lung tissue, tissue of benign pulmonary diseases and non-small cell
      lung cancer (NSCLC) tissue. PATIENTS AND METHODS: Tumor tissue and surrounding
      carcinoma-free lung tissue samples were obtained from 91 patients with NSCLC who
      had undergone surgery in the years 2005-2007 as well as lung tissue from 12
      patients operated on for 'benign' bullous emphysema or interstitial lung disease.
      The mRNA was isolated from the tissues and the expression of mRNA was assessed
      using a real-time RT PCR method. RESULTS: Significantly higher expression of MMP
      7, MMP-9 and TIMP-1 mRNA was demonstrated in the NSCLC tissue in comparison with
      the normal lung tissue from the same patients (p=0.0003, p<0.0001 and p=0.0018,
      respectively). Similar results for MMP-7, MMP-9 and TIMP-1 were found in the
      histological subgroups: squamous cell lung cancer vs. normal tissue (p=0.0198,
      p=0.0015 and p=0.0366, respectively), and adenocarcinoma vs. normal tissue
      (p=0.0045, p<0.0001 and p=0.0140, respectively). The expression of MMP-7 was
      found to be significantly higher in tumor tissue vs. lung tissue of the benign
      diseases (p=0.0086) and similar results were also recorded in the histological
      subgroups: squamous cell lung cancer vs. benign tissue (p=0.0171) and
      adenocarcinoma vs. benign tissue (p=0.0135). The expression of MMP-9 was
      significantly higher only in the adenocarcinoma subgroup vs. the benign tissue
      (p=0.0412). No differences in the expression of mRNA between stage IA and stages
      IB-IIIB of NSCLC were recorded. CONCLUSION: Significantly higher expression of
      MMP-7 and MMP-9 in tumor tissue than in the surrounding tissue or in benign lung
      disease tissue supports the notion of an important role of these
      metalloproteinases in the growth of lung carcinoma. TIMP-1 expression is
      increased only in carcinoma, but not in benign lung disease.

PMID- 19596922
TI  - Role of L-MYC polymorphism in oral squamous cell carcinoma in Turkey.
AB  - BACKGROUND: An association between restriction fragment length polymorphism
      (RFLP) of known oncogenes and a predisposition to develop cancer has been
      postulated. Our aim was to test the hypothesis that there was an association
      between the L-MYC S allele in oral squamous cell carcinoma (OSCC) and a
      predisposition for the disease. PATIENTS AND METHODS: The distribution of L-MYC
      polymorphism in 80 patients with OSCC was determined by polymerase chain reaction
      based RFLP and compared with that of 60 healthy controls. RESULTS: There was no
      significant difference between patients with OSCC and healthy controls. Patients
      with the L-MYC S allele and a positive family history of cancer were found to be
      1.74 times more at risk for OSCC than those with any other genotype (95%
      confidence interval=0.88-3.45). Moreover, tumor recurrence was higher among
      individuals carrying a L-MYC S allele than those with any other allele type.
      CONCLUSION: L-MYC polymorphism was not a significant marker for predicting
      susceptibility to OSCC in this population but may be a useful marker for
      identifying patient susceptibility to tumor recurrence and to developing OSCC,
      especially in individuals having a family history of cancer.

PMID- 19596923
TI  - Expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in
      human breast carcinoma cells and tissues.
AB  - BACKGROUND: The therapeutic effects of oral capecitabine are proposed to be
      determined by the equilibrium of two intratumoral metabolizing enzymes, namely
      thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). The
      present study aims to evaluate this hypothesis by in vivo experiments and
      immunohistochemical analysis in 31 cases of human breast carcinoma. MATERIALS AND
      METHODS: The effects of capecitabine on two breast carcinoma cell lines were
      evaluated by the status of both cell proliferation and apoptosis and mRNA levels
      of TP and DPD were also determined. TP and DPD status was determined by
      immunohistochemistry in 31 cases of breast carcinoma tissues and the results were
      compared with their clinicopathological parameters. RESULTS: The therapeutic
      efficacy of capecitabine in two cell lines was not related to the levels of TP
      and DPD mRNA expression. No statistically significant association was detected
      between the status of these enzymes and the clinicopathological factors.
      CONCLUSION: In vitro study demonstrated that capecitabine was effective against
      the BT-483 and MB-MDA-231 breast carcinoma cell lines used but the significance
      of the status of intratumoral TP and DPD in determining its therapeutic efficacy
      needs further studies.

PMID- 19596924
TI  - Abnormal expression of fibrinogen gamma (FGG) and plasma level of fibrinogen in
      patients with hepatocellular carcinoma.
AB  - Abnormal expression of genes has been related to progression of hepatocellular
      carcinoma (HCC). The present study investigated the mRNA expression of fibrinogen
      gamma (FGG) in HCC and levels of plasma fibrinogen of patients with HCC.
      MATERIALS AND METHODS: Northern blot and semiquantitative RT-PCR were performed
      to determine the mRNA transcription of FGG. The plasma fibrinogen was measured
      quantitatively by the von Clauss method. RESULTS: FGG was significantly up
      regulated at the mRNA level in the SMMC-7721 and HepG2 HCC cell lines. FGG mRNA
      transcript was also up-regulated in HCC tissues when compared to non-cancerous
      adjacent tissues as control. The laboratory investigation of blood samples from
      114 HCC patients showed significantly higher levels of plasma fibrinogen compared
      to healthy persons as control (3.75+/-1.41 vs. 2.90+/-0.46 g l(-1)) (p<0.01).
      Moreover, plasma fibrinogen increased progressively with the tumor clinical stage
      of HCC patients. By multivariate logistic regression analysis, a positive level
      of plasma fibrinogen was found to have a significant correlation with the
      presence of tumor thrombosis. CONCLUSION: FGG mRNA was expressed abnormally in
      HCC and elevated plasma fibrinogen may serve as a useful predictor of clinical
      progression of HCC patients.

PMID- 19596925
TI  - O6-Methylguanine-DNA methyltransferase hypermethylation modulated by 17beta
      estradiol in lung cancer cells.
AB  - BACKGROUND: Our recent report indicated that MGMT hypermethylation is more common
      in squamous cell carcinomas (SCC) in males, and smokers than in adenocarcinomas
      (ADC) in females, and nonsmokers. More interestingly, MGMT hypermethylation in
      SCC and ADC was pronouncedly influenced by gender factor, not by smoking status.
      We questioned whether 17beta-estradiol could modulate the machinery of promoter
      methylation to cause the gender difference of MGMT hypermethylation in lung
      cancer. MATERIALS AND METHODS: Two MGMT hypermethylated Ch27 and H1355 lung
      cancer cell lines were treated with or without 17beta-estradiol and the status of
      hypermethylation was examined by methylated specific methylation (MSP) as
      compared with both cells treated with demethylating agents, 5-AZA-dC (AZA) or
      TSA. RESULTS: Our data showed that 17beta-estradiol, similar to AZA, diminished
      the MGMT hypermethylation and restored MGMT mRNA expression, which was not
      observed in the case of TSA. Western blotting showed that 17beta-estradiol
      markedly reduced DNMT1 expression in Ch27 and H1355 cells, but slightly reduced
      HDAC1 expression. Consequently, acetylated H3 and H4 histone levels were slightly
      increased by 17beta-estradiol in both cell types. In addition, ChIP analysis
      revealed that 17beta-estradiol simultaneously diminished the binding activity of
      both proteins on the MGMT promoter of both cell lines. CONCLUSION: 17beta
      Estradiol decreased DNMT1 and HDAC1 protein expressions and their binding
      activity on MGMT promoter, and this may partially contribute to the gender
      difference of MGMT hypermethylation in lung cancer.

PMID- 19596926
TI  - Development of a novel cell-based assay to evaluate the malignant potential of
      cancer in vitro.
AB  - BACKGROUND: Metastasis is a leading cause of cancer death. To evaluate the
      complex metastatic process in vitro, an attempt was made to develop a cell-based
      assay (Can kit) that could evaluate the late stages of metastasis. MATERIALS AND
      METHODS: Two membrane chambers were set up of which the upper membrane chamber
      with 8 mum pores was covered with normal cell layers. Cancer cells were
      introduced to the upper chamber and after passing through the normal cell layers
      dropped through onto the lower chamber membrane where cancer colonies formed and
      were evaluated based on the reduction of transepithelial electrical resistance
      (TEER) with a Madin-Darby canine kidney (MDCK) cell monolayer. RESULTS: When two
      pairs of cancer cell lines, with different metastatic potentials in vivo, were
      applied to the Can kit assay, differences in potentials between the two cell
      lines in vitro were demonstrated. The reduction in the TEER was correlated with
      the total area of the cancer colonies and the production of matrix
      metalloproteinases (MMPs). CONCLUSION: A cell-based assay able to evaluate the
      malignant potential of cancer in vitro was developed and is considered to be
      useful for research and the clinical examination of cancer metastatic potential.

PMID- 19596927
TI  - Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma.
AB  - BACKGROUND: The prognostic significance of S100A as potential biomarker for
      breast cancer was reported; however, this finding has recently been challenged.
      Here, the aim was to assess whether S100A4 could also be a prognostic biomarker
      of lung cancer. MATERIALS AND METHODS: A specific high-titer anti-S100A4
      monoclonal antibody was developed. The utility and specificity of this antibody
      was validated by immunostaining experiments. The antibody was tested against a
      newly developed high-density tissue microarray including 400 lung cancer tissues
      to examine the clinico-pathological and prognostic significance of S100A4 in lung
      cancer. RESULTS: The staining of S100A4 was significantly associated with
      patients' poor prognosis in lung squamous cell carcinoma but not lung
      adenocarcinoma. CONCLUSION: S100A4 seems to be a prognostic biomarker of lung
      squamous cell carcinoma (5-year survival rate of 38.5% versus 7.4%, p<0.01), but
      not of adenocarcinoma.

PMID- 19596928
TI  - Preoperative chemoradiotherapy for esophageal cancer: factors associated with
      clinical response and postoperative complications.
AB  - BACKGROUND: The factors associated with the clinical results of preoperative
      chemoradiotherapy (CRT) for esophageal cancer and its effect on postoperative
      complications are still unclear. PATIENTS AND METHODS: The 686 patients with
      esophageal cancer were classified into 376 who received preoperative CRT (group
      I) and 310 who received surgery alone (group II). RESULTS: A multivariate
      analysis for group I patients revealed pathologically complete response to be a
      favorable prognostic factor. Preoperative use of cisplatin was significantly
      associated with pathological effect and patients' prognosis. Both pulmonary
      complications and anastomotic leakage more frequently developed in group I (16.0
      and 27.9%) than in group II (10.0%, p<0.05 and 16.5%, p<0.01, respectively). A
      multivariate analysis revealed preoperative CRT to be an independent factor of
      postoperative complications. CONCLUSION: Although preoperative CRT for esophageal
      cancer may be associated with postoperative complications, a pathologically
      complete response, which is associated with a cisplatin-based regimen, is
      critical for improving patient prognosis.

PMID- 19596929
TI  - Chemotherapy response evaluation in metastatic colorectal cancer with FDG PET/CT
      and CT scans.
AB  - BACKGROUND: [18F]-fluorodeoxyglucose with positron-emission tomography (PET) and
      computed tomography (CT) scans were used to assess morphological and metabolic
      tumour response after chemotherapy in metastatic colorectal cancer. PATIENTS AND
      METHODS: Twenty-five patients were evaluated after 4 courses of chemotherapy (+/
      target therapy), and among them 20 patients after 2 courses. Response Evaluation
      Criteria In Solid Tumors (RECIST) and European Organisazion for Research and
      Treatment of Cancer (EORTC) criteria were used to evaluate CT and PET
      respectively. RESULTS: Discrepancies between the two procedures were noted after
      4 courses of chemotherapy in patient-based analysis. Two morphologically complete
      responses (CR) were correlated with metabolic response. Seven morphological
      partial responses (PR) were evaluated as 3 metabolic PR, 2 CR and 1 progressive
      disease (PD). Seventeen cases of morphologically stable disease (SD) were
      evaluated as 3 metabolic CR, 13 PR and 1 PD. These discrepancies were confirmed
      in lesion-based analysis. Perfect concordance was noted between metabolic
      responses obtained after 2 and 4 cycles. CONCLUSION: Morphological and metabolic
      imaging does not permit concordant therapeutic assessment in metastatic
      colorectal cancer.

PMID- 19596930
TI  - Anaemia and other predictors of fatigue among patients on palliative therapy for
      advanced cancer.
AB  - The association of anaemia and other predictors of fatigue was studied in cancer
      patients on palliative treatment. A cohort of 128 consecutive patients (61 men
      and 67 women, mean age 63.6 years; range 36-85) was interviewed using the
      Edmonton Symptom Assessment System (ESAS) questionnaire, with 11 items describing
      cancer-related symptoms in visual analogue scale (VAS). Routine haematological
      samples were analysed at the time of interview. Both univariate and multivariate
      analyses were used to assess the independent predictors of fatigue. Out of the 10
      symptoms recorded, fatigue was the single most frequent, reported by 91.3% of the
      patients, followed by pain (74.8%), sleeplessness (78.0%) and depression (74.2%).
      Anaemia was a significant determinant of fatigue (p=0.040)(OR=5.09; 95% CI 1.013
      25.647). Out of the symptoms recorded, fatigue was significantly associated with
      depression (p=0.035), loss of appetite (p=0.016), anxiety (p=0.050), and
      sleeplessness (p=0.016). Total wellbeing was negatively associated with fatigue
      (OR=0.48, 95% CI 0.011-0.020)(p=0.0001). In multivariate analysis, anaemia was
      the most powerful independent predictor of fatigue, with OR=38.27 (95% CI 2.62
      559.19)(p=0.008), followed by sleeplessness (OR=14.06 95% CI 1.44-137.02 p=0.023)
      and loss of appetite (OR=10.30 95% CI 1.04-101.10, p=0.045). Fatigue was
      unrelated to sex or age, or to the type of cancer, or the treatment category.
      Fatigue was common among cancer patients on palliative care. The single most
      powerful independent explanatory factor of fatigue was anaemia, implicating a
      need for interventional studies.

PMID- 19596931
TI  - Discrepancies in expression and prognostic value of tumor markers in
      adenocarcinoma and squamous cell carcinoma in cervical cancer.
AB  - The expression of 11 tumor markers in 129 women with squamous cell compared to 31
      women with adenomatous cervical cancer was investigated to detect differences in
      expression. There was a significantly higher expression of p53, CD4, epidermal
      growth factor receptor (EGFR), CD44 and stratifin in squamous cell, compared to
      adenocarcinoma, while there was a higher expression of c-myc in adenocarcinoma. P
      53, cyclooxygenase-2 (Cox-2) and c-myc significantly correlated to prognosis in
      squamous cell carcinoma, but none of the 11 investigated tumor markers had any
      prognostic value in adenocarcinomas. The prognostic value of individual tumor
      markers differs with the histological subtype in cervical cancer.

PMID- 19596932
TI  - Insulin-like growth factor-binding protein-3 in osteosarcomas and normal bone
      tissues.
AB  - BACKGROUND: To better understand the significance of local insulin-like growth
      factor-binding protein 3 (IGFBP-3) in the development of osteosarcoma, IGFBP-3
      levels and subcellular localization were compared in biopsies from osteosarcomas
      and unaffected normal bone tissues. PATIENTS AND METHODS: IGFBP-3 levels were
      analyzed by immunohistochemistry in 21 osteosarcomas and 5 unaffected bone
      tissues. IGFBP-3 levels were compared for patient outcome. RESULTS: Mature
      osteocytes of normal bone tissues contained high levels of predominantly nuclear
      IGFBP-3, whereas only 50% of osteosarcomas contained IGFBP-3-positive tumor
      cells, with predominantly cytoplasmic IGFBP-3 staining. Comparison of IGFBP-3
      levels for patient outcome resulted in two groups. Patients with a low level of
      IGFBP-3 in osteosarcoma experienced a trend for a shorter survival time than did
      patients with a high level of IGFBP-3. CONCLUSION: Our results suggest that the
      levels and subcellular localization of local IGFBP-3 play a role in osteosarcoma
      development. Further prospective evaluation with higher clinical sample numbers
      might reveal a prognostic role for IGFBP-3 level in local tumors in patients with
      osteosarcoma.

PMID- 19596934
TI  - Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms.
AB  - BACKGROUND: Neuropathy is a common adverse effect of chemotherapy. The tricyclic
      antidepressant, amitriptyline, is a gold standard in the treatment of neuropathic
      pain. This double-blind, randomized placebo-controlled trial assessed the
      efficacy of amitriptyline to prevent chemotherapy-induced neuropathic symptoms.
      PATIENTS AND METHODS: Patients without previous neuropathy, who started
      chemotherapy with vinca alcaloids, platina derivatives or taxanes, were
      randomized to receive amitriptyline (target dose, 100 mg daily) or placebo for
      the duration of their chemotherapy. Chemotherapy-induced neuropathic symptoms
      were evaluated with a patient diary and after every third chemotherapy cycle with
      clinical examination. The diary data were transformed to a neuropathy score. A
      total of 114 patients fulfilling the inclusion criteria were randomly assigned to
      the treatment or control arm. RESULTS: There was no difference in the appearance
      of chemotherapy-induced neuropathic symptoms between the groups. In general, the
      intensity of neuropathic symptoms was mild. CONCLUSION: Amitriptyline does not
      prevent chemotherapy-induced neuropathy.

PMID- 19596933
TI  - New markers and multivariate models for prostate cancer detection.
AB  - Specificity of PSA has been enhanced by using molecular forms of PSA and free PSA
      (fPSA) such as percent free PSA (% fPSA), proPSA, intact PSA or BPHA and/or new
      serum markers. Most of these promising new serum markers like EPCA2 or ANXA3
      still lack confirmation of outstanding initial results or show only marginal
      enhanced specificity at high sensitivity levels. PCA3, TMPRSS2-ERG, and other
      analytes in urine collected after digital rectal examination with application of
      mild digital pressure have potential to preferentially detect aggressive PCa and
      to decrease the rate of unnecessary repeat biopsies. The combination of these new
      urinary markers with new and established serum markers seems to be most promising
      to further increase specificity of tPSA. Multivariate models e.g. artificial
      neural networks (ANN) or logistic regression (LR)-based nomograms have been
      recently developed by incorporating these new markers in several studies. There
      is generally an advantage to including new markers and clinical data as
      additional parameters to PSA and % fPSA within ANN and LR models. The results and
      unexpected pitfalls of these studies are shown.

PMID- 19596935
TI  - Pseudoprogression and MGMT status in glioblastoma patients: implications in
      clinical practice.
AB  - Pseudoprogression (PsPD) is a pathological feature recently reported by some
      authors in malignant glioma patients treated with radiotherapy in combination
      with temozolomide. In radiological imaging, it is shown as an increase in the
      size of the tumor lesion and contrast enhancement occurring within a few months
      from the completion of radio-chemotherapy without worsening of the neurological
      signs and symptoms. In 21%-50% of the patients, the same lesion disappears a few
      months after its appearance. In 12 glioblastoma patients treated with radio
      chemotherapy, 4 cases of early radiological progression without discontinuation
      of temozolomide treatment are reported. At the sunsequent tumor assessment, 2
      cases (13%) were revealed to be PsPD. The two patients who experienced PsPD had
      the longest progression and survival times of all patients. In both patients with
      PsPD, the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was found to
      be methylated. The PsPD phenomenon opens the prospect of a new era for the
      management of glioblastoma patients undergoing radio-chemotherapy.

PMID- 19596936
TI  - Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan)
      for the treatment of advanced colorectal cancer.
AB  - BACKGROUND: Lentinan (LNT) is an immune adjuvant medicine for advanced gastric
      cancer in Japan. Recently, an oral formulation of superfine dispersed lentinan
      (SDL) has become clinically available. To investigate the safety and
      effectiveness of SDL, a multi center clinical study in patients with advanced
      colorectal cancer was conducted. PATIENTS AND METHODS: Adverse events were
      assessed and the patients' quality of life (QOL) and the binding ability of
      peripheral blood monocytes (PBM) to LNT were also evaluated. RESULTS: Four grade
      2 adverse events associated with SDL treatment were observed among the 80
      patients. Adverse events associated with chemotherapy were observed in 9 out of
      the 64 chemotherapy-treated patients. Among the 48 patients assessed for QOL, the
      patients with low QOL scores before SDL treatment (n=23) reported a significant
      improvement in their QOL scores after 12 weeks of SDL administration. The rates
      of LNT-binding PBM in the QOL-improved group were significantly higher than those
      in the QOL-not-improved group (p<0.05). CONCLUSION: SDL was safe and effective
      for suppressing the adverse effects of chemotherapy as well as improving QOL. The
      binding ability of PBM to LNT appears to be a promising predictor of QOL
      improvement after SDL administration.

PMID- 19596937
TI  - Quantitative analysis of tumor-derived methylated RUNX3 sequences in the serum of
      gastric cancer patients.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Using real-time quantitative methylation
      specific PCR (RTQ-MSP), methylated RUNX3 sequences were quantified and the
      fractional concentrations of circulating tumor DNA in serum were determined,
      along with peripheral blood cells collected preoperatively, intraoperatively and
      postoperatively from 65 patients with gastric cancer. RESULTS: RTQ-MSP was
      sufficiently sensitive to detect RUNX3 methylation. Quantitative MSP data were
      expressed in terms of the methylation index, which was defined as the relative
      amount of methylated RUNX3 sequences divided by the concentration of methylated
      actin. High levels of methylated RUNX3 sequences were detected in the peripheral
      circulation of 29% (19 of 65) of the gastric cancer patients. The RUNX3
      methylation index was concordant with cancer stage, histology, lymphatic and
      vascular invasion, and was more sensitive than carcinoembryonic antigen (CEA) as
      a biomarker. Twenty-nine percent (19 out of 65) of preoperative serum samples had
      methylated RUNX3 sequences, ranging from 5.2 to 1625955 (median quantity=43 m
      index, sensitivity 95.5%, specificity 62.5%, AUC 0.8651). After surgical
      resection, the median RUNX3 methylation index in serum significantly decreased.
      These results demonstrate the clinical usefulness and effectiveness of peripheral
      blood RTQ-MSP for detecting and monitoring gastric cancer after treatment.
      Furthermore, 5 out of the 30 preoperative control samples of benign disease
      (cases of panperitonitis due to acute appendicitis or cholecystitis) showed
      transient RUNX3 methylation which decreased after the operation in accordance
      with recovery. CONCLUSION: Quantification of epigenetic changes in serum RUNX3
      methylation using RTQ-MSP is useful for the detection and monitoring of gastric
      cancer.

PMID- 19596938
TI  - Definitive conformal radiotherapy for localized prostate cancer: a long-term
      follow-up study.
AB  - BACKGROUND: The present study analyzed the clinical long-term outcome of patients
      with localized prostate cancer after definitive conformal radiotherapy with and
      without accompanying androgen deprivation (AD). PATIENTS AND METHODS: From 1996
      to 2000, 210 patients (median age: 69 years; range: 54-82 years) with a localized
      prostate cancer (T1/T2: 72%; initial PSA <10: 39%; Gleason <7: 65%) were treated
      at Hannover Medical School. Fourteen percent of the patients were classified as
      low risk (LR), 40% as intermediate risk (IR) and 43% as high risk (HR) according
      to the ASTRO consensus definition. All patients received a conformal radiotherapy
      of the prostate with a median total dose of 70.2 Gy (<65 Gy: 5%; 65-70 Gy: 36%
      and >70 Gy: 59%), 177 patients (84%) in combination with temporary AD (median
      duration 4 month). Biochemical failure after irradiation was defined as three
      consecutive serum PSA elevations in accordance to the ASTRO consensus statement
      from 1997. Long-term side-effects were evaluated on the basis of a standardized
      questionnaire. RESULTS: The median follow-up was 5.2 years (0.94 to 9.41 years);
      54 events (28%) were registered, and 41 patients (20%) were lost to follow-up.
      The 7-year overall survival (OS) was 75.6% without significant differences in the
      results regarding the three risk groups (LR: 84.6% vs. IR: 77.2% vs. HR: 73.5%).
      The 5- and 7-year biochemical disease free survival (bDFS) were 78.3% and 70.0%
      (LR: 84.6% /84.6% vs. IR: 75.5% /66.7% vs. HR: 77.7% /66.1%). CONCLUSION: This
      study confirms the findings of other investigators and encourages the
      continuation of risk-adapted treatment policy for localized prostate cancer
      modified by using higher radiation doses and long-term AD for selected patients
      with higher risk tumors.

PMID- 19596939
TI  - VEGF in patients with non-small cell lung cancer during combination chemotherapy
      of carboplatin and paclitaxel.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic
      factor related to tumor growth and metastasis. However, little is known about the
      clinical significance of circulating VEGF in cancer patients. PATIENTS AND
      METHODS: Eighteen patients with non-small cell lung cancer received chemotherapy
      using carboplatin and paclitaxel. Plasma levels of VEGF were analyzed at baseline
      and after 2 cycles of chemotherapy. RESULTS: Partial remission was observed in 3
      patients (16.7%), stable disease in 10 patients (55.6%) and progressive disease
      in 5 patients (27.8%). Patients with partial remission or stable disease had
      significantly lower levels of plasma VEGF than did patients with progressive
      disease, both at baseline (p=0.0341) and after 2 cycles of chemotherapy
      (p=0.0265). There were no significant changes of plasma VEGF during chemotherapy.
      CONCLUSION: Pretreatment plasma levels of VEGF are a useful marker for predicting
      disease control by chemotherapy.

PMID- 19596940
TI  - Does distance to treatment centre influence the rate of palliative radiotherapy
      in adult cancer patients?
AB  - Previous reports suggest that age, household income and travel distance from
      residence to treatment facility are barriers which influence access to
      radiotherapy. The purpose of this study was to analyse the utilisation of
      palliative radiotherapy in a health care system where the main goal is equal
      access despite place of residence. The Authors collected prospective data on the
      use of palliative radiotherapy in adult cancer patients over a 12-month period in
      2007/2008. All patients were treated in northern Norway and had unlimited, rapid
      access to treatment. Efforts were made to account for potential overuse. The
      patients were divided into three groups according to travel distance. The
      majority of irradiated patients had bone metastases, followed by non-bony
      thoracic targets and brain metastases. No statistically significant differences
      in the utilisation rates were detected, the latter ranging from 129 annual
      treatment courses per 100,000 inhabitants in the region furthest away from the
      hospital to 142 courses in that closest to it. The median age of the irradiated
      patients in the three groups was similar. In conclusion, these data suggest that
      the utilisation of palliative radiotherapy in a health care system without
      financial barriers to treatment no longer varies with distance between residence
      and hospital.

PMID- 19596941
TI  - Prospective study on neck dissection after primary chemoradiation therapy in
      stage IV pharyngeal cancer.
AB  - BACKGROUND: Definitive chemoradiation is a well-established option in the
      treatment of locally advanced squamous cell carcinoma of the head and neck. The
      intention of this study was to evaluate its efficacy on cervical lymph node
      metastases in a prospective study after a standardized protocol for
      chemoradiation (CRT) and histopathological evaluation, respectively. PATIENTS AND
      METHODS: The data of 25 patients (10 oropharynx, 15 hypopharynx) who received
      planned neck dissection after definitive chemoradiation for UICC stage IV
      carcinomas of the pharynx were analyzed. All patients were sonomorphologically
      staged positive for lymph nodes (3 patients: N1; 2 patients N2a; 7 patients N2b;
      9 patients N2c and 4 patients N3). A neck dissection was carried out 8.9+/-1.5
      weeks (range 6-13) post treatment. The specimens obtained from the different neck
      levels were histologically examined for viable tumour cells. RESULTS: Local
      control was achieved in 100% of all patients on endoscopy 9 weeks after the
      chemoradiation. In 14/25 patients (56%), still viable tumour tissue was found in
      the neck dissection (ND) specimen. Only one of these 14 patients (7%) was deemed
      suspicious for residual lymphadenopathy from clinical and diagnostic findings at
      re-staging after chemoradiation, the others were staged yN0. Postsurgical
      complications occurred in six patients (24%) such as bleeding and prolonged wound
      healing in one patient each and functional deficits in an additional four
      patients. One patient developed a scar recurrence seven months after surgery.
      CONCLUSION: Based on these findings, the ultimate efficacy of primary CRT should
      not be judged 8-10 weeks after the treatment. Therefore planned neck dissection
      should be performed no earlier than 12 weeks after primary CRT.

PMID- 19596942
TI  - Giant Basal cell carcinoma: clinicopathological analysis of 51 cases and review
      of the literature.
AB  - BACKGROUND: Giant basal cell carcinoma (GBCC) is an aggressive malignant
      neoplasm. Because of the rarity of the tumor and its recognized high risk of
      recurrence, there are no guidelines for its treatment. PATIENTS AND METHODS:
      Published articles in PubMed Central were carefully reviewed. Data from 48
      patients obtained from 30 individual articles were added to our 3 cases,
      producing a total number of 51 cases of GBCC. A clinical database was established
      in order to define the behavior of this tumor, prognostic factors and optimal
      treatment. RESULTS: GBCC mostly occurs in elderly male patients, with a peak
      incidence in the seventh decade of life. It develops as long-standing dermal
      tumor with mean disease duration of 14.5 years and is most commonly located on
      the back, followed by the face and upper extremity. The most common histological
      subtype is nodular. The average size at presentation is 14.77 cm in its largest
      diameter. The presence of metastasis at the time of presentation represents the
      most significant adverse prognostic factor. Local recurrence or metastasis
      develops in 38.3% of patients despite optimal therapy. The overall reported cure
      rate is 61.7% by a mean follow-up of 2 years. Wide local excision of the tumor
      with or without postoperative radiochemotherapy represents the optimal treatment.
      CONCLUSION: Optimal management of GBCC consists of wide local excision with
      histologically confirmed tumor-free margins, frequently followed by adjuvant
      therapy. In cases of lymphatic spread, a regional lymphadenectomy is also
      necessary. In addition, consideration should be given to a close and long-term
      follow-up because of the high rate of locoregional recurrence.

PMID- 19596943
TI  - Novel strategy of anti-angiogenic therapy for uterine cervical carcinomas.
AB  - In uterine cervical carcinomas, lymph node metastasis, recognized as a common
      form of metastasis, and recurrence after curative resection are critical to
      patient prognosis. The growth of secondarily spreading and initial recurrent
      lesions must be suppressed to improve patient prognosis. Chemotherapy and
      radiation are often not very specific to cancer cells and produce severe effects
      on normal cells, especially bone marrow and renal cells. On the other hand, anti
      angiogenic therapy is specific to the rapidly growing vascular endothelial cells
      in tumors, without any effect on slow growing vascular endothelial cells and
      other normal cells. Therefore, anti-angiogenic therapy should be an excellent
      strategy to suppress the growth of secondarily spreading and initial recurrent
      lesions. However, if a particular angiogenic factor is suppressed by anti
      angiogenic therapy for a long period, another angiogenic factor may be induced by
      linked alternative angiogenic pathway, a process recognized as tolerance. The
      angiogenic factor expression and the effects of angiogenic transcription factors
      in uterine cervical carcinomas are herein reviewed and novel therapeutic trends
      are introduced.

PMID- 19596944
TI  - Impact of interstitial lung disease on survival for patients with non-small cell
      lung cancer.
AB  - BACKGROUND: Interstitial lung disease (ILD) and lung cancer are two of the most
      common respiratory diseases. The aim of this study was to demonstrate the
      prognostic significance of presence of ILD in patients with non-small cell lung
      cancer (NSCLC). PATIENTS AND METHODS: All the patients with NSCLC who were
      admitted to our hospitals over a 23-year period up to 2008 were retrospectively
      analyzed. RESULTS: During the study period, 2,165 NSCLC patients were
      consecutively admitted to our hospitals. Among them, 53 (2.4%) patients were
      diagnosed as having both NSCLC and ILD. In uni- and multivariate analysis, female
      gender, early stage, good PS, and surgery were favorable prognostic factors. The
      presence of ILD was confirmed as an unfavorable prognostic factor. CONCLUSION:
      Existing ILD adversely affects the outcome of NSCLC. When deciding whether or not
      to offer a standard therapy which may increase treatment-related mortality, the
      patient's medical condition, including ILD, should be taken into consideration.

PMID- 19596945
TI  - Side-effects of pre-operative epirubicin-paclitaxel therapy in primary breast
      cancer associated with tumor biology.
AB  - BACKGROUND: The objective of this analysis is to identify relationships between
      side-effects, tumor biological factors and response to pre-operative epirubicin
      and paclitaxel therapy in primary breast cancer. PATIENTS AND METHODS: The study
      was completed for 38 primary breast cancer patients (M0) who received pre
      operative epirubicin and paclitaxel chemotherapy. Anemia was controlled by
      epoetin alfa and did not cause deviations from the planned chemotherapy schedule.
      RESULTS: There were no severe adverse events, cardiotoxicity or neutropenia.
      Patients with negative estrogen or progesterone receptors, or high KI-67 suffered
      more alopecia, while HER2 overexpressing patients had less severe nausea.
      CONCLUSION: This pre-operative chemotherapy regimen was well tolerated on the
      whole; side-effect profiles were correlated with tumor biological factors and
      also with response.

PMID- 19596946
TI  - Cisplatin-Ifosfamide-gemcitabine as salvage chemotherapy in ovarian cancer
      patients pretreated with platinum compounds and Paclitaxel.
AB  - BACKGROUND: The role of combination chemotherapy regimens in the management of
      ovarian cancer patients with tumors previously exposed to platinum compounds and
      paclitaxel has not yet been defined. The present phase II study evaluated the
      activity and toxicity of a gemcitabine-ifosfamide-cisplatin combination in the
      aforementioned group of patients. Given the in vitro and in vivo synergism
      between the three agents, it was believed that using a three-drug combination
      would overcome tumor resistance to cisplatin. PATIENTS AND METHODS: Twenty-four
      patients were enrolled in the study. The median age was 56 years and the median
      performance status 1. Eight (34%) had potentially platinum-sensitive, 6 (24%) had
      primary platinum-resistant and 10 (42%) patients had secondary platinum-resistant
      tumors. Treatment consisted of gemcitabine 1 g/m(2) i.v. on days 1 and 8,
      cisplatin 75 mg/m(2) i.v. over 2 h fractionated over days 8 and 9, and ifosfamide
      5 mg/m(2) i.v. over 1 h fractionated on days 8-9 with mesna uroprotection.
      Courses were administered every 3 weeks on an outpatient basis. Granulocyte
      colony-stimulating factor (G-CSF) was given at a dose of 5 microg/kg/day on days
      10-14. A median of 4 cycles were administered with the delivered dose intensity
      at 85% of the planned dose for the three agents. RESULTS: Among 24 patients
      evaluable for response and toxicity, there were 8 partial responses with a
      response rate of 33% (95% confidence interval 16.4-55%). Stable disease was
      recorded in 6 (25.7) and progressive disease in 10 (42%) patients. Subgroup
      analysis revealed a response rate of 50% in potentially platinum-sensitive, 16.5%
      in primary platinum-resistant and 30% in secondary platinum-resistant tumors. The
      median response duration was 5 months (range 3-12 months), the median time to
      progression 6 months (range 3-16 months) and the median survival 12 months (range
      3-24 months). Myelotoxicity was significant, with neutropenia grade 3 and 4
      occurring in 35% and 20% of patients, respectively. Four episodes (3.5% of all
      cycles) of febrile neutropenia were documented and were well managed with oral
      antibiotics and G-CSF continuation until complete recovery. Grade 1, 2 and 3
      peripheral neuropathy developed in 40%, 30%, and 10% of patients, respectively.
      CONCLUSION: The three-drug combination demonstrated a significant effectiveness
      in potentially platinum-sensitive tumors and a moderate efficacy in platinum
      resistant tumors. The regimen, although myelotoxic, is tolerable with G-CSF
      support. Further investigation via comparative studies is required to define any
      superiority of the present regimen over doublets of the three agents in this
      group of patients.

PMID- 19596947
TI  - Preoperative leukocytosis, anemia and thrombocytosis are associated with poor
      survival in non-small cell lung cancer.
AB  - BACKGROUND: Previous studies have reported any prognostic impact of preoperative
      leukocytosis, anemia and thrombocytosis in non-small cell lung cancer (NSCLC).
      The significance of the combined use of these 3 abnormal blood cell counts was
      investigated. PATIENTS AND METHODS: Two hundred and eighty-nine consecutive NSCLC
      patients were reviewed retrospectively. RESULTS: The patients with leukocytosis,
      anemia and thrombocytosis had significantly worse prognosis. The 5-year survival
      of the patients with all three of these abnormal blood cell counts was 25.0%,
      which was significantly poorer compared with that of the patients without any of
      these abnormal cell counts (78.23%). The 5-year survival of the patients with 1
      or 2 out of the three abnormal blood cell counts was an intermediate value. Both
      univariate and multivariate analyses indicated the independent prognostic impact
      of the use of these three abnormal blood cell counts combined. CONCLUSION: The
      use of leukocytosis, anemia and thrombocytosis combined might be useful for
      predicting the prognosis of NSCLC patients.

PMID- 19596948
TI  - Biological and clinical features in predicting efficacy of epidermal growth
      factor receptor tyrosine kinase inhibitors: a systematic review and meta
      analysis.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs), developed for patients with advanced non-small cell lung cancer (NSCLC),
      give modest results similar to those with chemotherapy. There is evidence of a
      greater survival benefit from TKIs in patients with certain molecular and
      clinical features, but results are conflicting. To assess the role of these
      factors in predicting TKI efficacy, a pooled analysis was performed on data from
      randomized trials in NSCLC. MATERIALS AND METHODS: An electronic search of all
      randomized trials comparing the efficacy or activity of TKIs and a pooled
      analysis were performed. The hazard ratio (HR) with 95% confidence interval (CI)
      was calculated for each level of the factors and an interaction test was used to
      detect differences in treatment effect related to the different levels. RESULTS:
      Of ten randomized trials identified, five were considered for analysis. Smoking
      was shown to be the only clinical factor to have a predictive effect (non
      smokers: overall survival (OS) HR 0.53, 95% CI 0.42-0.67; smokers: HR 0.91, 95%
      CI 0.81-1.02; p-value for interaction <0.001). A negative predictive value was
      suggested for K-ras mutations (K-ras(+): HR 1.97 95% CI 1.16-3.33; K-ras(-): HR
      0.79, 95% CI 0.59-1.05; p-value for interaction 0.003). CONCLUSION: At the
      present time, none of the biological features which have been evaluated in
      patients who have undergone therapy using TKIs is proven to be of predictive
      value; only K-ras mutations and smoking habits can be considered as a possible
      criteria for selection. Results of prospective randomized trials on biological
      markers are awaited.

PMID- 19596949
TI  - Clinical characteristics of laryngeal cancer in BRCA-1 mutation carriers.
AB  - BACKGROUND: The aim of this study was to analyze the occurrence of clinical
      features characteristic of breast cancer type 1 susceptibility protein (BRCA-1)
      dependent tumors in a series of BRCA-1 mutation carriers with laryngeal cancer.
      PATIENTS AND METHODS: The clinical features of five laryngeal cancer patients
      with BRCA-1 mutations registered in our center were analyzed for: sex, age at
      diagnosis, age at operation, tumor size and localization, histopathological
      subtype and grading, lymph node and distant metastases, mode of treatment and
      long term results of the therapy. RESULTS: The five patients were all men, with
      an average age at diagnosis of 52.4 years. The majority of the patients had
      clinical features typical of BRCA-1-dependent tumors: four out of the five
      patients had advanced staging at the time of diagnosis and in three of them the
      disorder disseminated within one year of follow-up. CONCLUSION: Since laryngeal
      carcinomas in men with BRCA-1 mutations show clinical features characteristic of
      BRCA-1 dependent tumors, it is reasonable to consider treatment modifications
      appropriate for this sub-group of tumors.

PMID- 19596950
TI  - Altered calcium metabolism in patients on long-term bisphosphonate therapy for
      metastatic breast cancer.
AB  - BACKGROUND: Bisphosphonates (BPs) are considered the standard of care in
      metastatic breast cancer (MBC) patients with bone metastases. Because the
      survival for these patients may be prolonged compared with those patients with
      visceral metastases, they may be prescribed BPs for several years. The effects of
      this long-term BP use on calcium metabolism in MBC patients have not previously
      been described. OBJECTIVES: The main objective of this study was to evaluate the
      effect of long-term BP use on calcium homeostasis in MBC patients. The secondary
      objective was to assess Vitamin D levels in these patients. MATERIALS AND
      METHODS: An exploratory analysis of serum calcium, parathyroid (PTH), and 25
      hydroxycholecalsiferol (25-(OH)D) levels and their inter-relationships was
      undertaken in 46 MBC patients who had been on prolonged BP therapy. These results
      were compared to a historical control group of 420 patients without bone or
      mineral disease who were matched for gender, age, baseline renal function and
      season of seological testing. RESULTS: Patients were similar in the two groups
      with no significant difference in mean age, baseline creatinine or season of
      testing. Serum calcium was no different between the two groups. However, PTH was
      significantly higher in MBC patients, compared to controls (5.7 vs. 4.8 pmol/L,
      p=0.043). Linear regression analysis showed that PTH was significantly higher in
      the MBC group at lower serum calcium levels and fell sharply with increasing
      serum calcium levels (p=0.0001). Among the patients with MBC, 62% had suboptimal
      levels of vitamin D and 18% were found to have insufficient or deficient levels
      (25-(OH)D < 40 nM) despite taking dietary supplementation. CONCLUSION: In MBC
      patients with prolonged BP use, there appears to be a state of
      hyperparathyroidism similar to that seen with BP use in benign bone disease.
      Supplementation with 400 IU per day of Vitamin D per day was not sufficient to
      correct this metabolic abnormality.

PMID- 19596951
TI  - Decrease of E-cadherin expression in canine cutaneous histiocytoma appears to be
      related to its spontaneous regression.
AB  - BACKGROUND: Canine cutaneous histiocytoma (CCH) is an epidermotropic tumour of
      Langerhans cells, most frequent in young dogs, which undergoes spontaneous
      regression. MATERIALS AND METHODS: E-cadherin immunoexpression was analysed in
      ninety-three CCH, categorized according to Cockerell and Slauson (1976) criteria
      into four histological groups, representing different stages of tumour
      regression. RESULTS: All tumours expressed membranous E-cadherin both in
      keratinocytes, and in tumoural cells and no differences were noted among the
      histological groups analysed. However, the intensity of the E-cadherin
      immunolabeling decreased in the presence of lymphoid infiltration and varied
      significantly among the groups considered (p<0.0001). CONCLUSION: This study
      strongly suggests a down-regulation of E-cadherin expression in CCH pathogenesis
      and progression. The loss of E-cadherin expression might represent an activation/
      maturation process of the tumoural cells constituting a switch for CCH
      regression.

PMID- 19596952
TI  - Fifty-five minimally invasive Esophagectomies: a single centre experience.
AB  - BACKGROUND: Minimally invasive esophagectomy is an evolving alternative to the
      open technique with the goal of providing efficient oncological therapy while
      minimizing morbidity by diminishing surgical trauma. PATIENTS AND METHODS: Fifty
      five consecutive esophagectomies with a minimally invasive approach were included
      in the calculations. The patients' demography, surgical, histopathological and
      survival outcomes were analyzed, and surgical/ non-surgical morbidity rates
      calculated. RESULTS: In 47% of the patients, a laparoscopic-thoracoscopic
      approach, and in 53% minimally invasive hybrid procedures were performed. The
      overall conversion rate to open surgery was 5.5%. Major surgical complications
      occurred in 26% and major non-surgical morbidity in 13% of the patients. The
      curative resection rate was 87% with a median number of investigated lymph-nodes
      of 17.5. The 1-year disease-free survival and overall survival were 73% and 88%,
      respectively. No hospital mortality occurred. CONCLUSION: Minimally invasive
      oncological resection in patients with esophageal cancer is feasible and provides
      the potential of reducing postoperative morbidity and enhancing the oncological
      outcome even when a learning curve is included.

PMID- 19596953
TI  - Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors,
      mechanisms of carcinogenesis and prevention strategies.
AB  - Patients with long-standing ulcerative colitis and Crohn's disease have an
      increased risk of developing colorectal cancer and patients with small intestinal
      Crohn's disease are at increased risk of small bowel adenocarcinoma. Colorectal
      cancer appearing on the ground of inflammatory bowel disease is the result of a
      process which is believed to begin from no dysplasia progressing to indefinite
      dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive
      adenocarcinoma, although colorectal cancer can arise without proceeding through
      each of these steps. Ulcerative colitis patients with total proctocolectomy and
      ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal
      pouch, although the anal transition zone should be monitored periodically,
      especially if chronic pouchitis is present with associated severe villous
      atrophy. Concerning the risk factors predisposing to colorectal cancer in the
      setting of ulcerative colitis or Crohn's disease, it seems that the risk
      increases with longer duration and greater anatomic extent of colitis, the degree
      of inflammation, and the presence of primary sclerosing cholangitis and family
      history of colorectal cancer. Concerning the mechanisms of carcinogenesis, it is
      now well established that the molecular alterations responsible for sporadic
      colorectal cancer, namely chromosomal instability, microsatellite instability and
      hypermethylation, also play a role in colitis-associated colon carcinogenesis.
      Chemoprevention strategies include the administration of agents such as
      aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins, the
      exact role of which remains to be further elucitated.

PMID- 19596954
TI  - Individual patient based meta-analysis of lentinan for unresectable/recurrent
      gastric cancer.
AB  - BACKGROUND: In the present study, the effect of immunochemotherapy with lentinan
      compared with that of chemotherapy alone was evaluated in patients with advanced
      gastric cancer through individual patient data (IPD) meta-analysis. MATERIALS AND
      METHODS: Based on a computerized and manual search, all eligible centrally
      randomized controlled trials (RCT) which compared chemotherapy regimens with or
      without lentinan administration for advanced gastric cancer patients were
      included. RESULTS: In total, 650 IPD from 5 trials were available. Lentinan
      significantly prolonged the overall survival (stratified log-rank p=0.011). The
      overall hazard ratio (HR) was 0.80 (95% confidence interval=0.68-0.95) and there
      was no heterogeneity between trials. Additionally, lentinan was possibly more
      effective in patients with lymph-node metastasis than in non-node metastasis
      patients (P for interaction=0.077). CONCLUSION: The addition of lentinan to
      standard chemotherapy offers a significant advantage over chemotherapy alone in
      terms of survival for patients with advanced gastric cancer.

PMID- 19596955
TI  - Gefitinib plus paclitaxel after failure of gefitinib in non-small cell lung
      cancer initially responding to gefitinib.
AB  - BACKGROUND: New therapeutic modalities are needed for non-small cell lung cancer
      (NSCLC) patients whose tumors have become resistant to gefitinib. PATIENTS AND
      METHODS: Between 2005 and 2008, 16 NSCLC patients, who had been previously
      treated with gefitinib and evaluated as partial response or complete response
      according to the response evaluation criteria in solid tumors (RECIST), received
      gefitinib plus paclitaxel. Paclitaxel was administered at 60 mg/m(2) on days 1, 8
      and 15 every 4 weeks, and gefitinib was administered at 250 mg/day from the first
      day of administration of paclitaxel. RESULTS: The response rate and disease
      control rate were 13% and 75%, respectively. The median progression-free survival
      (PFS) and median overall survival were 4.3 months and 8.1 months, respectively.
      The toxicities were mild, and there were no treatment-related deaths.
      CONCLUSIONS: Gefitinib plus paclitaxel after failure of gefitinib exhibits
      activity and acceptable toxicity.

PMID- 19596956
TI  - DYRK2 expression may be a predictive marker for chemotherapy in non-small cell
      lung cancer.
AB  - BACKGROUND: The possibility of a dual-specificity tyrosine-(Y)-phosphorylation
      regulated kinase gene, DYRK2, predicting benefit from chemotherapy for patients
      with recurrent non-small cell lung cancer (NSCLC) was investigated. MATERIALS AND
      METHODS: Forty patients with recurrent disease after surgery received several
      combinations of platinum-based chemotherapy. The chemotherapy effectiveness was
      evaluated according to RECIST (response evaluation criteria in solid tumors).
      Immunohistochemical (IHC) analysis was used to determine the expression of DYRK2.
      RESULTS: Although the response rates between the two groups did not show
      statistical differences, the disease control rate of the DYRK2-positive group (15
      out of 17, 88%) was significantly different from the DYRK2-negative group (8 out
      of 23, 35%, p=0.001). The median time to the progression (TTP) of disease was
      significantly different between the two groups (310 days in the positive group,
      120 days in the negative, HR=2.12, 95% CI=[1.1-4.09], p=0.024). Multivariate
      analysis showed that negative DYRK2 expression was a strong predictor of disease
      progression (HR=3.01, 95% CI=[1.45-6.26], p=0.003). CONCLUSION: Patients with
      high DYRK2 expression could be good candidates for chemotherapy.

PMID- 19596958
TI  - Gastrointestinal stromal tumor with chondroid differentiation.
AB  - Gastrointestinal stromal tumors are mesenchymal neoplasms of the gastrointestinal
      tract that represent less than 1% of all GI tumors. Here the case of such a
      tumour that, in addition to the classical features, also displayed chondroid
      differentiation is reported. Chromosomal abnormalities were also investigated.

PMID- 19596957
TI  - Efficacy of a lumbo-peritoneal shunt for meningeal carcinomatosis refractory to
      gefitinib treatment.
AB  - A 51-year-old female presented with left facial palsy. She had adenocarcinoma of
      the lung with multiple brain metastases. The primary tumor regressed after
      treatment with gefitinib, however, neurological symptoms progressed rapidly
      because of meningeal carcinomatosis, when a deletion mutation in exon 19 of the
      epidermal growth factor receptor in cells from her cerebrospinal fluid was
      detected. After performing lumbo-peritoneal shunting, her symptoms improved
      dramatically and she had been well without peritoneal dissemination for 15
      months, continuing gefitinib treatment. Finally, she died 18 months after lumbo
      peritoneal shunting. A T790M acquired-resistance mutation in exon 20 of the
      epidermal growth factor receptor was found from her mesenteric lymph nodes and
      cerebrospinal fluid at autopsy. A lumbo-peritoneal shunt might be considered for
      meningeal carcinomatosis refractory to gefitinib treatment without an emergence
      of a T790M mutation.

PMID- 19596959
TI  - Dominance of EGFR and insignificant KRAS mutations in prediction of tyrosine
      kinase therapy for NSCLC patients stratified by tumor subtype and smoking status.
AB  - BACKGROUND: Therapy by tyrosine kinase inhibitors (TKI) has become inevitable in
      treatment of advanced NSCLC. Mutations in EGFR and KRAS genes have been
      identified as the main potential predictive and prognostic factors. Here the
      clinical implications of EGFR/KRAS mutations in patients from two separate trials
      treated with gefitinib or erlotinib are analysed. PATIENTS AND METHODS: A total
      of 360 patients (269 gefitinib and 91 erlotinib) were evaluated. Mutations in
      EGFR (exon 19 and 21) and KRAS (codons 12 and 13) and their impact on response
      and survival with respect to tumor subtype and smoking status were assessed.
      RESULTS: Adenocarcinomas revealed 399 days to progression (TTP) and 548 days
      overall survival (OS) for EGFR mutated vs. 119 days to progression and 137 days
      survival for non-mutated, p<0.0001 (TTP) and p=0.0001 (OS). No EGFR effect was
      recorded for squamous cell tumors. For smoking status, both EGFR-mutated smokers
      and non-smokers profited from TKI therapy. Smokers: 243 vs. 122 days (mutated vs.
      non-mutated), p=0.0284 (TTP) and 244 vs. 126 days, p=0.0396 (OS); non-smokers:
      390 vs. 71 days, p<0.0001, (TTP) and 548 vs. 135 days, p<0.0001 (OS). KRAS
      mutation in tumors did not result in a poorer prognosis in the subtype-selected
      groups, nor did it present as a negative factor in smokers. CONCLUSION: EGFR
      mutations possess statistical significance for a better therapy response and
      longer survival in all patients with adenocarcinomas (smokers as well as non
      smokers). KRAS does not seem an "a priori" negative factor for TKI-based
      treatment of NSCLC.

PMID- 19596960
TI  - Docetaxel and S-1 as a first-line treatment in patients with advanced or
      recurrent gastric cancer.
AB  - BACKGROUND: The safety and efficacy of docetaxel plus S-1 combination
      chemotherapy as a first-line treatment in patients with advanced or recurrent
      gastric cancer was verified retrospectively. PATIENTS AND METHODS: Eighteen
      patients with advanced or recurrent gastric cancer were enrolled. The regimen
      used was intravenous docetaxel, 40 mg/m(2), on day 1 and oral S-1, 80
      mg/m(2)/day, on days 1-14 every three weeks. RESULTS: In total 101 cycles were
      administered. One and 11 patients achieved complete and partial responses, while
      six and zero patients showed stable and progressive disease, respectively. The
      median time to progression (TTP) and median overall survival were 7.0 and 14.3
      months, respectively. Neutropenia was the most common grade 3/4 hematological
      toxicity. Nausea and stomatitis were the most common grade 3 nonhematological
      toxicities. No treatment-related death was observed. CONCLUSION: Docetaxel plus S
      1 combination is an active and tolerable regimen as a first-line treatment in
      patients with advanced or recurrent gastric cancer.

PMID- 19596961
TI  - Complete pelvic lymphadenectomy in patients with clinical early, grade I and II
      endometrioid corpus cancer.
AB  - AIM: To investigate the risk of pelvic lymph node metastasis in patients with a
      preoperative diagnosis of early endometrial cancer with favorable histological
      characteristics, assessed by complete pelvic lymphadenectomy. PATIENTS AND
      METHODS: A total of 108 patients with clinical early endometrioid grade I or II
      endometrial carcinoma underwent complete pelvic lymphadenectomy between 2001
      2007. Only cases with at least 15 nodes histologically examined were included.
      All operations were performed by the same team. The preoperative tumor histology
      was compared with the final pathological findings. The incidence of pelvic nodal
      involvement was estimated in relation to the final grade and depth of myometrial
      invasion in halves. RESULTS: The median age of patients was 63 years. In the
      final histology, 10 tumors (9.3%) of non-endometrioid histology were found. The
      discordance between pre- and postoperative tumor grade was 32.4%, with 24.1%
      being upgraded. Nine patients (8.3%) had poorly differentiated tumors and 23
      (21.3%) deep (>50%) myometrial invasion in the final pathology. A total of 11
      patients (10.2%) had pelvic nodal metastasis. The rate of lymph node metastasis
      in relation to final grade I and II and myometrial invasion was as follows: grade
      I, 1.8% (inner half 0%, outer half 14.3%); grade II, 15.9% (inner half 12.1%
      outer half 27.3%). Overall 19.4% of patients were upstaged at surgery.
      CONCLUSION: A significant proportion of patients presenting with early
      endometrial cancer of optimal characteristics will have a more advanced disease
      at surgical staging. Complete pelvic lymphadenectomy may increase the possibility
      of detecting metastatic disease in the lymph nodes.

PMID- 19596962
TI  - Prospective pilot-study of combined bipolar radiofrequency ablation and
      application of bone cement in bone metastases.
AB  - BACKGROUND: The purpose of this study was to determine the efficacy and safety of
      radiofrequency ablation (RFA) of bone metastases of breast cancer and to compare
      RFA alone and RFA with additional bone cement application. The primary objectives
      were to compare pain reduction and quality of life during long-term follow-up in
      a prospective pilot study. PATIENTS AND METHODS: Sixteen female patients with
      painful spinal bone metastases of human breast cancer were included in this
      prospective pilot study (mean age 59.5 years, range 52 - 69 years). RFA was
      performed with computed tomographic guidance and under local anesthesia. A
      bipolar and impedance-controlled radiofrequency system was used. Following RFA,
      bone cement was injected into the necrosis cavity in half of the patients (n=8).
      Pain, quality of life and complications were evaluated. Mean follow-up time was
      20.4 months (range 8-36). Paired comparison procedures were used for analysis of
      the results. A review of the literature was carried out. RESULTS: In both groups
      (RFA alone and RFA with additional bone cement application), pain was reduced
      significantly (mean reduction of pain 51.7%, p=0.0065). Quality of life was
      improved up to 61%. All procedures were performed without side-effects and
      complications. Imaging showed a complete ablation of the bone tumor in all
      patients. No local tumor progression was seen. CONCLUSION: RFA is a safe and
      effective option in the palliative therapy of bone tumors. Application of bone
      cement into the necrosis cavity has no significant additional effect on the
      reduction of pain and the improvement in quality of life. In selected cases with
      big bone defects, combining RFA and bone cement application is a useful option to
      stabilize the bone.

PMID- 19596963
TI  - Brain metastases from epithelial ovarian cancer: overview and optimal management.
AB  - Central nervous system involvement is a rare finding in the management of
      epithelial ovarian cancer with an incidence between 1-2%. A sharp rise in the
      incidence has been widely and repeatedly proclaimed for nearly two decades now,
      but has to be treated with scepticism after a careful review of the current
      literature. Brain metastases from ovarian cancer are known to be related to a
      very poor prognosis. Since brain imaging is not part of the routine follow-up
      care for ovarian cancer patients, and since CA-125--one of the standard tools-
      cannot be relied upon to detect central nervous system relapse, brain lesions are
      mostly traced by unspecific neurological symptoms only. Several prognostic
      factors are still being discussed today. But only a high performance status and
      the absence of an extra cranial disease at the time of CNS relapse have been
      accepted throughout the current literature as having a highly significant
      positive impact on survival. In the past, therapeutic efforts have focused on
      symptom palliation with corticosteroids and whole-brain radiation therapy (WBRT).
      During the last years several other therapy options have evolved from encouraging
      efforts made by several study groups, including chemotherapy, neurosurgery and
      radiosurgery. It has been shown that a multi-modal approach, combining these
      strategies, promises the best prolongation of survival and in some cases even
      resulted in long-term remissions. The present article gives an overview of brain
      metastases in epithelial ovarian cancer and discusses the current treatment
      options.

PMID- 19596964
TI  - Evidence-based perioperative management: strategic shifts in times of fast track
      surgery.
AB  - Changes in perioperative management is an ever evolving subject. The primary aim
      is to improve patient care and more recently to increase economic efficacy. Data
      from various randomized studies have caused a shift from traditional care
      concepts towards evidence based multimodal treatment strategies. They may lead to
      dramatic changes in perioperative patient care such as the routine use of
      nasogastric decompression, mechanical bowel preparation and established nutrition
      schemes. Further aspects of modern perioperative patient care include epidural
      analgesia, antibiotic prophylaxis, intraoperative fluid management and early
      mobilization. It has been generally accepted that these multimodal treatment
      concepts also known as "fast track surgery" show no differences in patient
      morbidity while significantly reducing patient discomfort and duration of
      hospitalization. However, despite the evidence-based superiority, widespread
      implementation has not yet occurred. The aim of this review is to highlight and
      discuss current changes and to show future perspectives of perioperative
      treatment strategies.

PMID- 19596965
TI  - Pros and cons of intraperitoneal chemotherapy in the treatment of epithelial
      ovarian cancer.
AB  - Development of the pros and cons of intraperitoneal (IP) chemotherapy in the
      treatment of epithelial ovarian cancer based on the most prominent data published
      on the evolution of IP chemotherapy and on experience with this therapeutic
      strategy in clinical routine. The literature published on IP chemotherapy in
      ovarian cancer between 1970 and 2008 was identified systematically by computer
      based searches in MEDLINE and the Cochrane Library. Furthermore, a preliminary
      analysis of data recorded during an observational nationwide multicenter study of
      the Austrian AGO on IP-IV chemotherapy using the GOG-172 treatment regimen was
      performed. The literature review unequivocally revealed a significantly greater
      toxicity for IP than for intravenous (IV) cisplatin-based chemotherapy. However,
      according to a Cochrane meta-analysis, IP-IV administration of chemotherapy is
      associated with a 21.6% decrease in the risk for death. In agreement with earlier
      reports, the most frequently mentioned side-effects in the Austria-wide
      observational study were long-lasting neurotoxicity, abdominal pain, fatigue,
      gastrointestinal and metabolic toxicities, and catheter-related complications.
      Most of these toxicities were identified as mirroring the toxicity profile of
      high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV
      regimen with cisplatin/paclitaxel was changed to an alternative schedule
      comprising carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15)
      completely administered via the IP route. This treatment was better tolerated and
      quality of life was significantly less compromised. However, neutropenia and
      thrombocytopenia were the limiting side-effects of this IP regimen. In cases
      where optimal cytoreduction with residual disease <or=1 cm was achieved during
      primary surgery and disease was confined to the peritoneal cavity, IP
      chemotherapy should be given serious consideration, even at the expense of
      significantly increased, but manageable toxicity.

PMID- 19596966
TI  - Surgical outcome and survival analysis of young patients with primary epithelial
      ovarian cancer.
AB  - OBJECTIVE: The mean age of diagnosis of epithelial ovarian cancer (EOC) is in the
      mid-fifties. Limited data exist about the clinical outcome of patients aged below
      35 years. The aim of the present study was to evaluate the cancer-related
      characteristics, intraoperative findings, surgical outcome and survival in this
      group of young women. PATIENTS AND METHODS: Within the period between 01/1989 and
      06/2008, all consecutive patients younger than 35 years with histologically
      proven EOC were enrolled into this study. All patients' characteristics,
      intraoperative and histological findings, as well as survival data were
      systematically analyzed using a validated prospective documentation tool for the
      intraoperative and postoperative data collection. RESULTS: Thirty-one patients
      younger than 35 years at primary diagnosis (mean age: 28.65 years; range: 15-35)
      were identified among 397 patients with primary EOC (7.8%). FIGO-stage III
      (45.2%) was the most common tumor stage and serous-papillary (54.8%) was the most
      frequent histological type. A complete tumor resection was achieved in 18
      patients (58.1%) with only few postoperative complications. In a mean follow-up
      period of 44.65 months, 9 patients (29%) died. Mean progression-free survival was
      74.72 months (95% CI: 34.22-115.22), whereas mean overall survival was 148.15
      months (95% CI: 91.63-204.68) and hence longer than the equivalent survival data
      of the total patient collective. CONCLUSION: Primary EOC in young patients
      (<or=35 years old) seems to be associated with a higher overall and progression
      free survival, higher platinum-sensitivity rate and a rather better clinical
      outcome than older patients. Further multicenter studies are warranted to
      evaluate the underlying reasons for these observations.

PMID- 19596967
TI  - Prognostic significance of CA-125 in the management of patients with recurrent
      epithelial ovarian carcinoma selected for secondary cytoreduction.
AB  - BACKGROUND: Despite radical surgical and chemotherapeutic treatment of ovarian
      cancer, the majority of patients develop recurrence and die due to progressive
      disease. Routine measurement of the tumor marker CA-125 is often used in the
      follow-up management. However, the role of preoperative CA-125 as a prognostic
      factor before secondary cytoreduction of relapsed ovarian cancer has not been
      determined. PATIENTS AND METHODS: CA-125 serum concentration and relevant clinico
      pathological variables were analyzed regarding their potential prognostic impact
      in patients selected for secondary cytoreduction of recurrent epithelial ovarian
      cancer. RESULTS: In total, 48 patients underwent secondary cytoreduction at the
      University Medical Center Hamburg-Eppendorf between 1996 and 2004 and 36 patients
      were evaluable for serum CA-125 concentration. Median age was 60 years (range 30
      78 years) and median relapse-free survival before secondary cytoreduction was 18
      months. The median time to progression after secondary surgery was 22 months
      (range 1-100 months), and median overall survival was 26 months (range 1-100
      months). Serum CA-125 at the time of secondary cytoreduction was elevated (>35
      kU/L) in 30 of 36 patients (81%) with a median of 212 kU/L (range 6-3866 kU/L).
      Multivariate analysis did not reveal a prognostic significance for preoperative
      CA-125. The only independent prognostic factors of improved survival were
      progression-free interval before secondary cytoreduction (p=0.047) and minimal
      residual disease after secondary cytoreduction (p=0.024). CONCLUSION: Although
      most patients had elevated serum CA-125 at the time of secondary cytoreductive
      surgery, CA-125 had no prognostic relevance.

PMID- 19596968
TI  - Surgical management of multiple bilateral fibroadenoma of the breast: the Ribeiro
      technique modified by Rezai.
AB  - BACKGROUND: Fibroadenomas are hyperplasia arising from the terminal ductulo
      lobular unit and adjacent tissue of the breast. As single fibroadenoma, even
      giant ones are easily manageable, however multiple fibroadenomas pose a
      particular challenge. CASE REPORT: In 1971, Liacyr Ribeiro described his new
      technique for reduction mammaplasty. Four years later, the first 20 cases were
      published. This technique was introduced by Rezai in oncoplastic surgery. With
      free hand design, preoperative marking is performed- and the inferior pedicle
      modulated. RESULTS: Selective resection of more than seventy fibroadenomas was
      performed on two patients. The technique allowed a modelling of the breast like a
      mastopexy through the inferior pedicle. CONCLUSION: Multiple fibroadenomas of the
      breast are safely removable with the Ribeiro technique modified by Rezai.

PMID- 19596969
TI  - Venous coupler for free-flap anastomosis.
AB  - Free-flap surgery has become a routine procedure in breast reconstruction. The
      microvascular surgical anastomosis remains one of the technically sensitive
      aspects of free-tissue transfers. Between December 2006 and September 2007, 12
      anastomoses were performed with a venous coupling device from Synovis. There were
      no free-flap failures. Venous congestion occurred in only one case and was
      managed successfully with leeches. No major complications were observed. The
      Synovis venous coupling device system allowed a time-efficient and safe venous
      anastomosis in breast reconstruction.

PMID- 19596970
TI  - Pros and cons for systemic therapy in recurrent ovarian cancer.
AB  - Due to the high recurrence rates of ovarian carcinoma, the treatment of recurrent
      disease is currently one of the most challenging topics in the clinical setting.
      Ovarian cancer patients who do not respond to initial chemotherapy or who relapse
      after achieving a response are generally incurable. Treatment goals after failure
      of first-line treatment for ovarian cancer include: (a) controlling or preventing
      disease-related symptoms, (b) maintaining quality of life by choosing an
      effective treatment with low toxicity potential, and (c) prolonging progression
      free survival. In contrast to the adjuvant situation in which prospective
      randomized phase III trials have established the current standard, only a few
      randomized trials are available for patients with recurrent disease. In addition,
      a series of agents has been shown to have clinical activity in recurrent ovarian
      cancer, including topotecan, pegylated liposomal doxorubicin, gemcitabine and
      oral etoposide. It has also been demonstrated that re-treatment with a platinum
      drug and taxane has been associated with a significant clinical activity in
      patients with "sensitive" (treatment-free interval >6 months) recurrent disease.
      The role of antihormonal therapy is still unclear. These possible treatments for
      recurrent ovarian cancer require prospective randomized trials comparing
      efficacy, toxicity and quality of life.

PMID- 19596971
TI  - Controversies in the management of ovarian cancer--pros and cons for lymph node
      dissection in ovarian cancer.
AB  - Up-front maximal surgical effort towards cytoreduction with the primary goal of
      maximum tumour resection is one of the cornerstones in the multimodal management
      of ovarian cancer. Despite the prognostic relevance of lymph node metastasis,
      there is a great debate about the role of pelvic and para-aortic lymph node
      dissection. In early-stage ovarian cancer, lymph node dissection is required to
      make an accurate clinical staging according to the FIGO classification and to
      select adequate adjuvant therapy. The effect of lymph node dissection on
      progression-free survival and overall survival in patients with advanced ovarian
      cancer is still unknown. There has only been one randomized trial which favoured
      systematic lymph node dissection instead of lymph node sampling due to
      significantly better progression-free survival, but there was no difference in
      overall survival. Patients with postoperative tumour residuals are unlikely to
      benefit from this procedure. The German AGO has now initiated the first study in
      advanced ovarian cancer (LION) which compares the value of systematic lymph node
      dissection with no lymph node resection in patients without any visible tumour
      residuals. Until these data are in fact available, patients with advanced ovarian
      cancer should be informed in detail about the pros and cons of systematic lymph
      node dissection.

PMID- 19596972
TI  - Circulating hTERT DNA in early breast cancer.
AB  - BACKGROUND: The objective of the study was to quantify the human telomerase
      reverse transcriptase (hTERT) gene in the circulating DNA of patients with
      primary breast cancer (BC) and to test its correlation with clinical parameters
      of the disease. PATIENTS AND METHODS: One hundred and twenty-one BC patients, 30
      patients with fibroadenoma (NBC) and 50 healthy women were enrolled. RESULTS: The
      level of hTERT in the plasma was significantly different in BC, NBC and controls
      (p<0.01), showing a sensitivity of 50% and specificity of 90% in the ability to
      detect malignancy. The circulating hTERT DNA was significantly different in the
      estrogen receptor (ER)(+)/progesterone receptor (PgR)(+) compared to the ER(
      )/PgR(-) patients (p=0.03). Higher hTERT levels were associated with higher human
      epidermal growth factor receptor (HER)-2/Neu expression: score 0-1 vs. score 2+
      (p=0.01) and vs. score 3+ (p=0.02). Finally, hTERT was significantly inversely
      correlated with the carbohydrate antigen (CA) 15.3 serum level (p=0.001).
      CONCLUSION: Circulating hTERT DNA has a better diagnostic value than CA 15.3 in
      early breast cancer disease and could be a possible candidate as a tumor marker
      in patients with infiltrating ductal carcinoma positive to steroid hormonal
      receptor and with amplification of HER-2/Neu.

PMID- 19596973
TI  - Salvage chemotherapy with oxaliplatin and capecitabine for breast cancer patients
      pretreated with anthracyclines and taxanes.
AB  - There is no standard treatment for breast cancer patients whose tumors have been
      exposed both to anthracyclines and taxanes. Oxaliplatin shows synergism with 5
      fluorouracil (5-FU) and capecitabine is an oral prodrug of 5-FU with known
      efficacy in pretreated patients. This phase II trial studied the efficacy and
      toxicity of the oxaliplatin-capecitabine combination as salvage treatment in
      breast cancer patients pretreated with anthracyclines and taxanes. Patients
      received oxaliplatin 80 mg/m(2) on day 1 followed by oral capecitabine 1800
      mg/m(2) divided in two doses for 7 days every two weeks for a maximum of twelve
      courses or until disease progression. Twenty-eight patients were evaluable for
      efficacy and toxicity. Objective responses (all partial) were documented in 9
      patients [32%; 95% confidence interval (CI): 13-51.2%]. Responses were documented
      at all metastatic sites. The median response duration was 5 months (range 3-9),
      median time to progression was 4.5 months (range 2-10) and median overall
      survival was 10 months (range 2-18). Myelotoxicity was minimal with grade 3
      thrombocytopenia as the main toxicity. Hand-foot syndrome was well tolerated. The
      present regimen was well tolerated with a rather moderate effectiveness but very
      significant for this group of patients. Further studies where the combination
      could be compared with single agent capecitabine are warranted.

PMID- 19596974
TI  - Impact of catechol-O-methyltransferase (COMT) gene polymorphism on promoter
      methylation status in gastric mucosa.
AB  - DNA methylation is one of the major events in the early process of gastric
      carcinogenesis and also occurs in non-neoplastic gastric mucosa. Catechol-O
      methyltransferase (COMT) catalyzes the methylation of various endobiotic and
      xenobiotic substances, and protects DNA from oxidative damage. The association
      between a common functional polymorphism of COMT Val158Met and DNA methylation
      status in the stomach was investigated. PATIENTS AND METHODS: One hundred and
      sixty-nine gastric mucosa samples from non-cancer patients were obtained by
      endoscopy. The promoter methylation status of p14 and p16 was determined by
      methylation-specific PCR (MSP). The COMT Val158Met polymorphism was detected by
      PCR-restriction fragment length polymorphism (RFLP). RESULTS: CpG island
      methylation was observed in 32.5% of the p14, and 37.9% of the p16. The
      methylation status of both p14 and p16 was not associated with gender or age,
      while p16 methylation was strongly associated with Helicobacter pylori infection
      (OR=4.71, 95% CI=2.35-9.46, p<0.0001). The Val/Val genotype held a significantly
      higher risk of p16 methylation (OR=3.27, 95% CI=1.05-10.25, p=0.0418).
      CONCLUSION: The COMT polymorphism may influence the susceptibility to gene
      methylation in the gastric mucosa. The promoter CpG island of p16 gene, but not
      of p14 may be one of the specific regions whose methylation is closely influenced
      by the COMT polymorphism.

PMID- 19596975
TI  - Phase II study of weekly paclitaxel as a second-line treatment for S-1-refractory
      advanced gastric cancer.
AB  - BACKGROUND: We retrospectively evaluated the efficacy of weekly paclitaxel
      therapy as second-line treatment for patients with advanced gastric cancer that
      was refractory to S-1. PATIENTS AND METHODS: In total, 33 patients received
      intravenous paclitaxel (80 mg m(-2)) on days 1, 8 and 15 as part of a 4-week
      cycle. RESULTS: Eight patients showed a partial response, 11 showed stable
      disease and 14 showed disease progression. In total, 171 courses (mean=5.2;
      range=3-16) were administered. Thirteen cases subsequently underwent third-line
      treatment. The median survival time and time to progression from the time of
      second-line treatment was 8.0 months and 4.2 months, respectively. The most
      common haematological toxicities were leukopenia and neutropenia. Non
      haematological toxicities were generally mild to moderate and controllable.
      CONCLUSION: This study showed favourable therapeutic outcomes for advanced
      gastric cancer patients. However, it will be necessary to confirm the advantages
      of paclitaxel treatment for S-1-refractory advanced gastric cancer in a larger
      population.

PMID- 19596976
TI  - Phase I study of capecitabine, carboplatin and intensity-modulated radiation
      therapy for head and neck cancer.
AB  - BACKGROUND: To determine the maximally tolerated dose (MTD) of capecitabine when
      given concomitantly with carboplatin and intensity-modulated radiation therapy
      (IMRT) for treatment of localized stage III/IV squamous cell carcinomas of the
      head and neck (HNSCC). PATIENTS AND METHODS: After six weeks of induction
      chemotherapy with capecitabine and carboplatin, patients received a second course
      with concomitant IMRT. The MTD for capecitabine during chemoradiation was
      determined by a standard phase I trial design. RESULTS: Nine out of the eleven
      patients qualified for chemoradiation. With weekly carboplatin AUC=1.5 and IMRT,
      the MTD of capecitabine was 850 mg/m(2)/day when given in divided doses on days 1
      14 and 22-35. The dose-limiting toxicity was myleosuppression and other adverse
      effects were modest. Eight patients experienced complete response after
      chemoradiation and seven remain relapse-free after 34 months. CONCLUSION:
      Capecitabine, carboplatin, and IMRT given as described were well tolerated by
      HNSCC patients and in this pilot study produced a promising rate of disease
      control.

PMID- 19596977
TI  - Every genome sequence needs a good map.

PMID- 19596978
TI  - IL-8 regulates mucin gene expression at the posttranscriptional level in lung
      epithelial cells.
AB  - Airway inflammation and mucus hypersecretion/overproduction/obstruction are
      pathophysiological characteristics of cystic fibrosis, asthma, and chronic
      obstructive pulmonary disease. Up-regulation of airway mucin genes by
      inflammatory/immune response mediators is one of the major contributors to mucin
      overproduction. IL-8, a potent proinflammatory mediator and neutrophil
      chemoattractant, is present at high levels in the airway secretions of such
      patients. In this study, the effects of IL-8 on expression of two major airway
      mucin genes, MUC5AC and MUC5B, were evaluated. IL-8 increased the mRNA abundance
      of both mucin genes in two human respiratory tract-derived cell lines (A549 and
      NCI-H292) in a time- and concentration-dependent manner. IL-8 also increased
      MUC5AC and MUC5B mRNA levels in primary normal differentiated human bronchial
      epithelial cells, with a high concentration of IL-8 required to increase MUC5B
      mRNA levels. IL-8 did not transcriptionally up-regulate MUC5AC gene expression,
      but rather increased the stability of the MUC5AC transcript, suggesting
      regulation at the posttranscriptional level. In addition, IL-8 altered the levels
      of RNA-binding proteins to specific domains in the 3'-untranslated region of the
      MUC5AC transcript. Taken together, these data indicate that the IL-8-induced
      binding of RNA-binding proteins to the 3'-untranslated region of MUC5AC is a
      potential mechanism for regulating MUC5AC gene expression at the
      posttranscriptional level, thus suggesting a new role whereby IL-8 sustains mucin
      gene expression in inflamed airways.

PMID- 19596979
TI  - Dying and necrotic neutrophils are anti-inflammatory secondary to the release of
      alpha-defensins.
AB  - Neutrophils are recruited to sites of injury but their timely removal is thought
      to be vital to prevent exacerbating inflammation. In addition, the recognition of
      apoptotic cells by cells of the innate immune system provides potent anti
      inflammatory and anti-immunogenic signals. In this article, we describe how human
      neutrophils dying by apoptosis or necrosis release anti-inflammatory peptides,
      the alpha-defensins. This family of small cationic peptides effectively inhibits
      the secretion of multiple proinflammatory cytokines and NO from macrophages, the
      main innate immune cell found at sites of chronic inflammation. In addition, the
      systemic administration of necrotic neutrophil supernatants and alpha-defensins
      protects mice from a murine model of peritonitis. Hence. their effects may be far
      reaching and serve to kill microbes while regulating a potentially tissue
      destructive inflammatory response.

PMID- 19596980
TI  - Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced
      arthritis.
AB  - Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate
      (S1P). S1P plays a critical role in angiogenesis, inflammation, and various
      pathologic conditions. To date, two mammalian isoenzymes, SphK1 and SphK2, have
      been identified. Although both SphK1 and SphK2 share overall homology and produce
      the common product, S1P, it has been proposed they display different unique and
      separate functions. In this study, we examined the role of SphK1 and SphK2 in a
      murine collagen-induced arthritis model by down-regulating each isoenzyme via
      specific small interfering RNA (siRNA). Prophylactic i.p. administration of SphK1
      siRNA significantly reduced the incidence, disease severity, and articular
      inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA
      also down-regulated serum levels of S1P, IL-6, TNF-alpha, IFN-gamma, and IgG2a
      anti-collagen Ab. Ex vivo analysis demonstrated significant suppression of
      collagen-specific proinflammatory/Th1 cytokine (IL-6, TNF-alpha, IFN-gamma)
      release in SphK siRNA-treated mice. Interestingly, mice received with SphK2 siRNA
      develop more aggressive disease; higher serum levels of IL-6, TNF-alpha, and IFN
      gamma; and proinflammatory cytokine production to collagen in vitro when compared
      with control siRNA recipients. Together, these results demonstrate the distinct
      immunomodulatory roles of SphK1 and SphK2 in the development of inflammatory
      arthritis by regulating the release of proinflammatory cytokines and T cell
      responses. These findings raise the possibility that drugs which specifically
      target SphK1 activity may play a beneficial role in the treatment of inflammatory
      arthritis.

PMID- 19596981
TI  - Flexible stereospecific interactions and composition within nucleoprotein
      complexes assembled on the TCR alpha gene enhancer.
AB  - During thymocyte maturation, enhancers of genes encoding for TCRdelta (Tcrd) and
      TCRalpha (Tcra), Edelta(8), and Ealpha, work as a developmental switch
      controlling transition from Tcrd to Tcra activity at the Tcrad locus. Previous
      experiments revealed that an Ealpha fragment, Talpha1-Talpha2, which constitutes
      a well-characterized compact nucleoprotein structure led to premature activation
      of V(D)J recombination compared with that observed for the entire Ealpha or
      Talpha1-Talpha4. These experiments indicated that Talpha3-Talpha4 collaborates
      with factors bound to Talpha1-Talpha2 for the strict developmental regulation of
      Tcra rearrangement. The compact enhanceosome created on Talpha1-Talpha2 explained
      the molecular basis for requirement of intact Talpha2 TCF/LEF and ets sites for
      enhancer function. We have created a mutant version of Ealpha, EalphaMC, in which
      Edelta myb and runx sites have been substituted for Talpha2 runx and ets sites,
      that argues against the notion of a requirement for strict Ealpha enhanceosome
      structure for function. EalphaMC resulted in a very potent enhancer indicating
      that stereospecific interactions among proteins that form an Ealpha enhanceosome
      are rather flexible. Activation of V(D)J recombination by EalphaMC during
      thymocyte development resulted, however, to be premature and indistinguishable
      from that of Talpha1-Talpha2. These results indicate that Talpha3-Talpha4 itself
      is not sufficient to impart a developmental delay to a chimeric "early" enhancer,
      and indicate the need for functional collaboration between Talpha2 runx/ets sites
      binding proteins and proteins bound to Talpha3-Talpha4 for proper developmental
      activation. The possibility of assembly of distinct sets of proteins on Ealpha
      might represent a more flexible form of information processing during thymocyte
      development.

PMID- 19596982
TI  - Cutting edge: Limiting MHC class II expression to dendritic cells alters the
      ability to develop Th2- dependent allergic airway inflammation.
AB  - In allergic airway inflammation, dendritic cells (DCs) are required for Th2
      generation, recruitment, and activation in the respiratory tract. DCs have been
      shown to be necessary and sufficient for the induction of Th1 immune responses.
      In Th2 immunity and allergic airway inflammation, the ability of a DC to function
      as the sole APC has not been tested. We show that CD11c/A(beta)(b) mice with MHC
      class II expression restricted to CD11c-expressing DCs develop airway
      neutrophilia rather than allergic airway inflammation. Although CD11c/A(beta)(b)
      mice are capable of Th2 recruitment and activation in the lung, Th2 priming in
      CD11c/A(beta)(b) mice results in IFN-gamma production. Effective Th2 generation
      and allergic airway inflammation was achieved in CD11c/A(beta)(b) mice after
      treatment with anti-IFN-gamma. These studies show that DCs alone cannot drive the
      development of Th2 cells but require an additional MHC class II signal to
      stimulate effective Th2 immunity.

PMID- 19596984
TI  - TREM-1 activation alters the dynamics of pulmonary IRAK-M expression in vivo and
      improves host defense during pneumococcal pneumonia.
AB  - Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of TLR
      mediated inflammation during bacterial infections. Thus far, TREM-1 is primarily
      associated with unwanted signs of overwhelming inflammation, rendering it an
      attractive target for conditions such as sepsis. Respiratory tract infections are
      the leading cause of sepsis, but the biological role of TREM-1 therein is poorly
      understood. To determine the function of TREM-1 in pneumococcal pneumonia, we
      first established TREM-1 up-regulation in infected lungs and human plasma
      together with augmented alveolar macrophage responsiveness toward Streptococcus
      pneumoniae. Mice treated with an agonistic TREM-1 Ab and infected with S.
      pneumoniae exhibited an enhanced early induction of the inflammatory response
      that was indirectly associated with lower levels of negative regulators of TLR
      signaling in lung tissue in vivo. Later in infection, TREM-1 engagement altered
      S. pneumoniae-induced IRAK-M (IL-1R-associated kinase-M) kinetics so as to
      promote the resolution of pneumonia and remarkably led to an accelerated
      elimination of bacteria and consequently improved survival. These data show that
      TREM-1 exerts a protective role in the innate immune response to a common
      bacterial infection and suggest that caution should be exerted in modulating TREM
      1 activity during certain clinically relevant bacterial infections.

PMID- 19596983
TI  - Maternal exposure to secondhand cigarette smoke primes the lung for induction of
      phosphodiesterase-4D5 isozyme and exacerbated Th2 responses: rolipram attenuates
      the airway hyperreactivity and muscarinic receptor expression but not lung
      inflammation and atopy.
AB  - Airway hyperreactivity (AHR), lung inflammation, and atopy are clinical signs of
      allergic asthma. Gestational exposure to cigarette smoke (CS) markedly increases
      the risk for childhood allergic asthma. Muscarinic receptors regulate airway
      smooth muscle tone, and asthmatics exhibit increased AHR to muscarinic agonists.
      We have previously reported that in a murine model of bronchopulmonary
      aspergillosis, maternal exposure to mainstream CS increases AHR after acute
      intratracheal administration of Aspergillus fumigatus extract. However, the
      mechanism by which gestational CS induces allergic asthma is unclear. We now show
      for the first time that, compared with controls, mice exposed prenatally to
      secondhand CS exhibit increased lung inflammation (predominant infiltration by
      eosinophils and polymorphs), atopy, and airway resistance, and produce
      proinflammatory cytokines (IL-4, IL-5, IL-6, and IL-13, but not IL-2 or IFN
      gamma). These changes, which occur only after an allergen (A. fumigatus extract)
      treatment, are correlated with marked up-regulated lung expression of M1, M2, and
      M3 muscarinic receptors and phosphodiesterase (PDE)4D5 isozyme. Interestingly,
      the PDE4-selective inhibitor rolipram attenuates the increase in AHR, muscarinic
      receptors, and PDE4D5, but fails to down-regulate lung inflammation, Th2
      cytokines, or serum IgE levels. Thus, the fetus is extraordinarily sensitive to
      CS, inducing allergic asthma after postnatal exposure to allergens. Although the
      increased AHR might reflect increased PDE4D5 and muscarinic receptor expression,
      the mechanisms underlying atopy and lung inflammation are unrelated to the PDE4
      activity. Thus, PDE4 inhibitors might ease AHR, but are unlikely to attenuate
      lung inflammation and atopy associated with childhood allergic asthma.

PMID- 19596986
TI  - Suplatast tosilate inhibits histamine signaling by direct and indirect down
      regulation of histamine H1 receptor gene expression through suppression of
      histidine decarboxylase and IL-4 gene transcriptions.
AB  - Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as
      sneezing, congestion, and rhinorrhea. Histamine plays important roles in
      eliciting AR symptoms. Up-regulation of the histamine H(1) receptor (H1R) and
      histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines
      are also involved in the pathogenesis of AR. We examined the effect of suplatast
      tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene
      2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R.
      Provocation with TDI increased nasal symptoms, HDC activity, the histamine
      content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in
      TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly
      suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs.
      Suplatast also suppressed HDC activity in the nasal mucosa and the histamine
      content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal
      cavity of normal rats up-regulated H1R mRNA, while intranasal application of
      histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation
      of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA
      elevation. These results suggest that suplatast alleviates nasal symptoms by
      inhibiting histamine signaling in TDI-sensitized rats through the suppression of
      histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL
      4 gene transcriptions, respectively.

PMID- 19596985
TI  - IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and
      limits intestinal inflammation in a murine model of colitis.
AB  - IL-27 limits CD4(+) T(H)17 cell development in vitro and during inflammatory
      responses in the CNS. However, whether IL-27-IL-27R interactions regulate the
      homeostasis or function of CD4(+) T cell populations in the intestine is unknown.
      To test this, we examined CD4(+) T cell populations in the intestine of wild-type
      and IL-27R(-/-) mice. Naive IL-27R(-/-) mice exhibited a selective decrease in
      the frequency of IFN-gamma producing CD4(+) T(H)1 cells and an increase in the
      frequency of T(H)17 cells in gut-associated lymphoid tissues. Associated with
      elevated expression of IL-17A, IL-27R(-/-) mice exhibited earlier onset and
      significantly increased severity of clinical disease compared with wild-type
      controls in a murine model of intestinal inflammation. Rag(-/-)/IL-27R(-/-) mice
      were also more susceptible than Rag(-/-) mice to development of dextran sodium
      sulfate-induced intestinal inflammation, indicating an additional role for IL-27
      IL-27R in the regulation of innate immune cell function. Consistent with this, IL
      27 inhibited proinflammatory cytokine production by activated neutrophils.
      Collectively, these data identify a role for IL-27-IL-27R interaction in
      controlling the homeostasis of the intestinal T cell pool and in limiting
      intestinal inflammation through regulation of innate and adaptive immune cell
      function.

PMID- 19596987
TI  - Microarray analysis of lymphatic tissue reveals stage-specific, gene expression
      signatures in HIV-1 infection.
AB  - Untreated HIV-1 infection progresses through acute and asymptomatic stages to
      AIDS. Although each of the three stages has well-known clinical, virologic, and
      immunologic characteristics, much less is known of the molecular mechanisms
      underlying each stage. In this study, we report lymphatic tissue microarray
      analyses, revealing for the first time stage-specific patterns of gene expression
      during HIV-1 infection. We show that although there is a common set of key genes
      with altered expression throughout all stages, each stage has a unique gene
      expression signature. The acute stage is most notably characterized by increased
      expression of hundreds of genes involved in immune activation, innate immune
      defenses (e.g., RIG-1, MDA-5, TLR7 and TLR8, PKR, APOBEC3B, 3F, 3G), adaptive
      immunity, and in the proapoptotic Fas-Fas ligand pathway. Yet, quite strikingly,
      the expression of nearly all acute stage genes return to baseline levels in the
      asymptomatic stage, accompanying partial control of infection. This transition
      from acute to asymptomatic stage is tied to increased expression of a diverse
      array of immunosuppressive genes (e.g., CLEC12B, ILT4, galectin-3, CD160, BCMA,
      FGL2, LAG3, GPNMB). In the AIDS stage, decreased expression of numerous genes
      involved in T cell signaling identifies genes contributing to T cell dysfunction.
      These common and stage-specific gene expression signatures identify potential
      molecular mechanisms underlying the host response and the slow, natural course of
      HIV-1 infection.

PMID- 19596988
TI  - Crystal-induced neutrophil activation: XI. Implication and novel roles of
      classical protein kinase C.
AB  - Monosodium urate (MSU) crystals are among the most potent proinflammatory
      stimuli, and an innate immune inflammatory response to the crystal surface is
      involved in the pathology of gouty arthritis. Furthermore, MSU crystals have
      recently been identified as danger signals able to induce the maturation of
      dendritic cells. Release of the crystals into the joint cavity promotes an acute
      inflammation characterized by a massive infiltration of neutrophils that leads to
      tissue damage. Protein kinase C (PKC) represents a family of serine/threonine
      kinases that play central signaling roles in multiple cellular responses. This
      family of kinases is divided into three subfamilies based on second messenger
      requirements: conventional (or classical), novel, and atypical. Despite their
      role in signal transduction, very little is known about the involvement of the
      PKC family in the inflammatory reaction induced by MSU crystals. In the present
      study, we show that MSU crystals activate conventional PKC isoforms, and that
      this activation is necessary for the MSU crystal-induced degranulation and
      generation of a chemotactic activity in the supernatants of MSU crystal
      stimulated human neutrophils. Evidence is also obtained that the tyrosine kinase
      Syk is a substrate of PKC and that the PKC-mediated serine phosphorylation of Syk
      is necessary to its interaction with the regulatory subunit of PI3K kinases (p85)
      and thus to the subsequent activation of these lipid kinases. These results
      suggest novel means of modulating neutrophil responses (through the specific
      regulation of PKC) during the acute phase of MSU crystal-induced inflammation.

PMID- 19596989
TI  - TNF-alpha preconditioning protects neurons via neuron-specific up-regulation of
      CREB-binding protein.
AB  - Despite being a proinflammatory cytokine, TNF-alpha preconditions neurons against
      various toxic insults. However, underlying molecular mechanisms are poorly
      understood. The present study identifies the importance of CREB-binding protein
      (CBP) in facilitating TNF-alpha-mediated preconditioning in neurons. Treatment of
      rat primary neurons with fibrillar amyloid beta1-42 (Abeta) resulted in the loss
      of CBP protein. However, this loss was compensated by TNF-alpha preconditioning
      as the expression of neuronal CBP was up-regulated in response to TNF-alpha
      treatment. The induction of CBP by TNF-alpha was observed only in neurons, but
      not in astroglia and microglia, and it was contingent on the activation of
      transcription factor NF-kappaB. Interestingly, antisense knockdown of CBP
      abrogated the TNF-alpha-mediated preconditioning of neurons against Abeta and
      glutamate toxicity. Similarly in vivo, preadministration of TNF-alpha in mouse
      neocortex prevented Abeta-induced apoptosis and loss of choline acetyltransferase
      positive cholinergic neurons. However, coadministration of cbp antisense, but not
      scrambled oligonucleotides, negated the protective effect of TNF-alpha against
      Abeta neurotoxicity. This study illustrates a novel biological role of TNF-alpha
      in increasing neuron-specific expression of CBP for preconditioning that may have
      therapeutic potential against neurodegenerative disorders.

PMID- 19596990
TI  - MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in
      macrophages by targeting TRAF6, IRAK1, and IRAK2.
AB  - Upon recognition of viral components by pattern recognition receptors, including
      TLRs and retinoic acid-inducible gene I (RIG-I)- like helicases, cells are
      activated to produce type I IFN and proinflammatory cytokines. These pathways are
      tightly regulated by host to prevent inappropriate cellular response, but viruses
      can down-regulate these pathways for their survival. Recently, identification of
      negative regulators for cytoplasmic RNA-mediated antiviral signaling, especially
      the RIG-I pathway, attract much attention. However, there is no report about
      negative regulation of RIG-I antiviral pathway by microRNAs (miRNA) to date. We
      found that vesicular stomatitis virus (VSV) infection up-regulated miR-146a
      expression in mouse macrophages in TLR-myeloid differentiation factor 88
      independent but RIG-I-NF-kappaB-dependent manner. In turn, miR-146a negatively
      regulated VSV-triggered type I IFN production, thus promoting VSV replication in
      macrophages. In addition to two known miR-146a targets, TRAF6 and IRAK1, we
      proved that IRAK2 was another target of miR-146a, which also participated in VSV
      induced type I IFN production. Furthermore, IRAK1 and IRAK2 participated in VSV
      induced type I IFN production by associating with Fas-associated death domain
      protein, an important adaptor in RIG-I signaling, in a VSV infection-inducible
      manner. Therefore, we demonstrate that miR-146a, up-regulated during viral
      infection, is a negative regulator of the RIG-I-dependent antiviral pathway by
      targeting TRAF6, IRAK1, and IRAK2.

PMID- 19596991
TI  - Trimer stabilization, oligomerization, and antibody-mediated cell surface
      immobilization improve the activity of soluble trimers of CD27L, CD40L, 41BBL,
      and glucocorticoid-induced TNF receptor ligand.
AB  - For many ligands of the TNF family, trimer stability and oligomerization status
      are crucial determinants of receptor activation. However, for the
      immunostimulatory ligands CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF
      receptor ligand (GITRL) detailed information regarding these requirements is
      lacking. Here, we comprehensively evaluated the effect of trimer stability and
      oligomerization on receptor activation by these ligands. Treatment with soluble
      Flag-tagged CD27L, 41BBL, and GITRL minimally activated receptor signaling, while
      Flag-CD40L was highly active. Oligomerization with anti-Flag Abs further enhanced
      the specific activity of Flag-CD40L 10-fold and of Flag-41BBL more than 200-fold,
      but it failed to activate Flag-CD27L and Flag-GITRL. We next investigated the
      relevance of trimer stability by introducing the tenascin-C (TNC) trimerization
      domain, yielding stabilized Flag-TNC-ligand trimers. Oligomerization with anti
      Flag Ab potently activated signaling by Flag-TNC-CD27L and Flag-TNC-GITRL and,
      albeit to a lesser extent, Flag-TNC-CD40L and Flag-TNC-41BBL. Forced
      hexamerization, by introducing an Ig Fc domain, revealed that hexameric
      derivatives of Flag-TNC-41BBL, Flag-CD40L, and Flag-TNC-GITRL all activate
      receptor signaling with high efficiency, whereas hexameric Flag-CD27L variant
      left inactive. Finally, we attempted to selectively activate receptor signaling
      on targeted cells, by using Ab fragment (single-chain fragment variable region,
      scFv)-ligand fusion proteins, an approach previously applied to other TNF
      ligands. Target cell surface Ag-selective activation was achieved for scFv-41BBL,
      scFv-CD40L, and scFv-GITRL, although the latter two displayed already significant
      activity toward Ag-negative cells. In conclusion, our data establish that
      trimeric CD40L is active, 41BBL requires hexamerization, GITRL requires trimer
      stabilization, and CD27L requires trimer stabilization and oligomerization.
      Furthermore, surface immobilization might be exploited to gain locally enhanced
      ligand activity.

PMID- 19596992
TI  - Novel MHC class I structures on exosomes.
AB  - Exosomes are nanometer-sized vesicles released by a number of cell types
      including those of the immune system, and often contain numerous immune
      recognition molecules including MHC molecules. We demonstrate in this study that
      exosomes can display a significant proportion of their MHC class I (MHC I)
      content in the form of disulfide-linked MHC I dimers. These MHC I dimers can be
      detected after release from various cell lines, human monocyte-derived dendritic
      cells, and can also be found in human plasma. Exosome-associated dimers exhibit
      novel characteristics which include 1) being composed of folded MHC I, as
      detected by conformational-dependent Abs, and 2) dimers forming between two
      different MHC I alleles. We show that dimer formation is mediated through
      cysteine residues located in the cytoplasmic tail domains of many MHC I
      molecules, and is associated with a low level of glutathione in exosomes when
      compared with whole cell lysates. We propose these exosomal MHC I dimers as novel
      structures for recognition by immune receptors.

PMID- 19596993
TI  - The p110delta isoform of phosphatidylinositol 3-kinase controls susceptibility to
      Leishmania major by regulating expansion and tissue homing of regulatory T cells.
AB  - Resistance to Leishmania major and most intracellular pathogens is usually
      associated with a strong T cell-mediated immunity, particularly a CD4(+) Th1
      response. Mice with an inactivating knock-in mutation in the p110delta isoform of
      PI3K (referred to as p110delta(D910A)) show severely impaired T cell responses.
      Because a strong T cell response is thought to mediate resistance to
      intracellular pathogens, we examined the outcome of L. major infection in
      p110delta(D910A) mice. Paradoxically, p110delta(D910A) mice on "resistant" and
      "susceptible" genetic backgrounds showed more robust resistance manifested as
      significantly reduced lesion size and accelerated parasite clearance. This
      enhanced resistance was associated with dramatically diminished immune responses,
      including impaired cell proliferation and effector cytokine (IFN-gamma and TNF)
      production. Interestingly, the ability of macrophages and dendritic cells from
      p110delta(D910A) mice to produce NO and destroy Leishmania parasites was similar
      to those of wild-type mice. We show that the enhanced resistance of
      p110delta(D910A) mice was due to impaired expansion and effector functions of
      regulatory T cells (Tregs). Adoptive transfer studies demonstrated that
      p110delta(D910A) mice lost their increased resistance when given enriched Tregs
      from wild-type mice. We suggest on the basis of these and further observations
      that the lack of this enzyme prominently affects Treg expansion and homing to
      infection sites, and that in the absence of Tregs, weak Th1 responses are capable
      of containing parasites and prevent pathology. We also suggest that temporary
      pharmacological inhibition of this enzyme may be a very effective form of
      treatment against cutaneous leishmaniasis.

PMID- 19596994
TI  - Cutting edge: Necrosis activates the NLRP3 inflammasome.
AB  - Cells undergoing necrosis release endogenous danger signals that possess
      proinflammatory potential. In this study we show that mature IL-1beta and IL-18
      are released by necrotic cells but not by apoptotic cells. We identify 7
      bromoindirubin-3'-oxime, an indirubin oxime derivative that induces necrosis, as
      a potent inducer of caspase-1 activation and release of mature IL-1beta and IL
      18. Inflammasome activation was triggered by other necrosis-inducing treatments
      but was not observed in response to apoptosis-inducing stimuli. Necrosis-induced
      inflammasome activation was mediated by the NLRP3 and ASC molecules. Release of
      IL-18 and IL-1beta in response to necrosis-inducing stimuli was observed in THP-1
      macrophages and the MSTO-211H human mesothelioma cell line independently of LPS
      priming. Using the in vivo model of naphthalene-induced airway epithelial cell
      injury, we showed that necrosis activates the ASC inflammasome in vivo. Our study
      identifies a new mechanism through which necrosis generates proinflammatory
      molecules that contributes to the sterile inflammatory response.

PMID- 19596995
TI  - Genetically detoxified pertussis toxin induces Th1/Th17 immune response through
      MAPKs and IL-10-dependent mechanisms.
AB  - Genetically detoxified pertussis toxin (dPT) maintains the protein structure and
      the immunological properties, but not the enzymatic activity. In search of an
      adjuvant able to direct polarization of T cells to induce/potentiate protective
      immune response to a variety of infectious disease, we investigated the role
      played by dPT on human dendritic cell-driven Th polarization and analyzed the
      intracellular signaling events. To reach these aims, we used a highly purified
      dPT preparation devoid of contamination and monocyte-derived dendritic cells, a
      well-characterized model to study ex vivo the polarization of the immune
      responses. First, we analyzed dPT-induced monocyte-derived dendritic cell
      maturation, longevity, and cytokine production and, in a second step, we analyzed
      TLR4/2 engagement by dPT, the connected signaling events, and their relevance to
      the skewing of Th cell polarization. These approaches allowed us to clarify some
      of the mechanisms that are responsible for dPT-driven regulation of T cell
      polarization. We demonstrated that dPT acts utilizing TLR4/TLR2 engagement, being
      the signaling induced by the former stronger. dPT, through a crucial role played
      by MAPK and IL-10, favors the expansion of the Th1/Th17 immunity. Indirect
      evidences indicated that dPT-induced Th17 expansion is counterregulated by the
      PI3K pathway. For its properties and being already used in humans as vaccine Ag
      in pertussis, dPT may represents a valid candidate adjuvant to foster immune
      protective response in vaccines against infectious diseases where Th1/Th17 are
      mediating host immunity.

PMID- 19596996
TI  - Selective expansion of the monocytic lineage directed by bacterial infection.
AB  - CCR2-mediated recruitment of Ly6C(high) monocytes is essential for defense
      against a range of microbial pathogens. Although our understanding of monocyte
      trafficking to inflammatory sites is increasing, how innate immune inflammation
      influences monocyte development and maturation during microbial infection remains
      undefined. Herein, we demonstrate that infection with the intracellular bacterial
      pathogen Listeria monocytogenes specifically and selectively promotes
      monopoiesis. Systemic infection with virulent L. monocytogenes induces marked
      proliferation of bone marrow monocyte precursors and results in depletion of
      myeloid progenitors. Proliferation of monocyte precursors correlates with the
      intensity of systemic infection and is unaffected by the density of monocytes in
      the bone marrow. Although MyD88/Trif-mediated signaling is not required for early
      emigration of the mature monocyte population from the bone marrow, replenishment
      of monocyte populations depends on MyD88/Trif. Our studies demonstrate that TLR
      mediated signals play an essential role in the maintenance of monocyte
      homeostasis during systemic bacterial infection.

PMID- 19596997
TI  - Cutting edge: SWI/SNF mediates antisense Igh transcription and locus-wide
      accessibility in B cell precursors.
AB  - The stepwise process of Ag receptor gene assembly, termed V(D)J recombination, is
      coordinated during lymphocyte development by sweeping changes in chromatin that
      permit or deny access to a single recombinase enzyme. We now show that
      switching/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes are
      recruited to the Igh locus by an enhancer-dependent process and that these
      complexes are essential for generating recombinase accessibility throughout the
      locus. Depletion of SWI/SNF in pro-B cells also inhibits antisense transcription
      through all clusters of Igh gene segments, a pioneering process that has been
      implicated in the initial opening of chromatin. We conclude that SWI/SNF
      complexes play multiple roles in Igh gene assembly, ranging from initial locus
      activation to the spreading and maintenance of chromatin accessibility over large
      V(H), D(H), and J(H) domains.

PMID- 19596998
TI  - Mycobacterium abscessus Glycopeptidolipids mask underlying cell wall phosphatidyl
      myo-inositol mannosides blocking induction of human macrophage TNF-alpha by
      preventing interaction with TLR2.
AB  - Mycobacterium abscessus causes disease in patients with structural abnormalities
      of the lung, and it is an emerging pathogen in patients with cystic fibrosis.
      Colonization of the airways by nontuberculous mycobacteria is a harbinger of
      invasive lung disease. Colonization is facilitated by biofilm formation, with M.
      abscessus glycopeptidolipids playing an important role. M. abscessus can
      transition between a noninvasive, biofilm-forming, smooth colony phenotype that
      expresses glycopeptidolipid, and an invasive rough colony phenotype that
      expresses minimal amounts of glycopeptidolipid and is unable to form biofilms.
      The ability of this pathogen to transition between these phenotypes may have
      particular relevance to lung infection in cystic fibrosis patients since the
      altered pulmonary physiology of these patients makes them particularly
      susceptible to colonization by biofilm-forming bacteria. In this study we
      demonstrate that rough variants of M. abscessus stimulate the human macrophage
      innate immune response through TLR2, while smooth variants do not. Temperature
      dependent loss or physical removal of glycopeptidolipid from the cell wall of one
      of the smooth variants leads to TLR2 stimulation. This response is stimulated in
      part through phosphatidyl-myo-inositol mannosides that are present in the cell
      wall of both rough and smooth variants. Mannose-binding lectins bind to rough
      variants, but lectin binding to an isogenic smooth variant is markedly reduced.
      This suggests that glycopeptidolipid in the outermost portion of the M. abscessus
      cell wall masks underlying cell wall lipids involved in stimulating the innate
      immune response, thereby facilitating colonization. Conversely spontaneous
      "unmasking" of cell wall lipids may promote airway inflammation.

PMID- 19596999
TI  - JAK3 inhibition significantly attenuates psoriasiform skin inflammation in CD18
      mutant PL/J mice.
AB  - JAK3, a member of the Janus kinase family, is predominantly expressed in
      hemopoietic cells and binds specifically to the common gamma chain of a subfamily
      of cytokine receptors that includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.
      Previous studies suggest that this tyrosine kinase plays key roles in mediating T
      cell functions, and inhibition of JAK3 has been shown to prevent graft rejection
      and decrease the severity of arthritis in rodent models. However, the functions
      of JAK3 in the development of skin immune responses and diseases such as
      psoriasis have not been determined. CD18 mutant PL/J mice develop spontaneous T
      cell-dependent psoriasiform skin disease with several similarities to human
      psoriasis. In this study, we treated mice with established skin disease with
      R348, a small molecule inhibitor of JAK3, and observed a marked attenuation of
      skin lesions following 6 wk of treatment. Histological analyses revealed major
      reductions of both epidermal and dermal lesion severity scores in R348-treated
      CD18-deficient PL/J mice compared with vehicle controls, which was associated
      with decreased CD4(+) T cell infiltration. In addition, systemic levels of IL-17,
      IL-22, IL-23, and TNF-alpha were significantly lower in mice receiving the
      compound, and T cells isolated from R348-treated mice also showed reduced
      phosphorylation of Stat5 after stimulation with IL-2. These findings suggest that
      small-molecule inhibitors of JAK3 may be useful in the treatment of inflammatory
      skin diseases such as psoriasis and strongly implicate JAK signaling events as
      important in the pathogenesis of this disease.

PMID- 19597000
TI  - Site-specific production of IL-6 in the central nervous system retargets and
      enhances the inflammatory response in experimental autoimmune encephalomyelitis.
AB  - IL-6 is crucial for the induction of many murine models of autoimmunity including
      experimental autoimmune encephalomyelitis (EAE), an animal model for multiple
      sclerosis. To establish the role of site-specific production of IL-6 in
      autoimmunity, we examined myelin oligodendrocyte glycoprotein immunization
      induced EAE in transgenic mice (GFAP-IL6) with IL-6 production restricted to the
      cerebellum. Myelin oligodendrocyte glycoprotein-immunized (Mi-) GFAP-IL6 mice
      developed severe ataxia but no physical signs of spinal cord involvement, which
      was in sharp contrast to Mi-wild type (WT) animals that developed classical EAE
      with ascending paralysis. Immune pathology and demyelination were nearly absent
      from the spinal cord, but significantly increased in the cerebellum of Mi-GFAP
      IL6 mice. Tissue damage in the cerebellum in the Mi-GFAP-IL6 mice was accompanied
      by increased total numbers of infiltrating leukocytes and increased proportions
      of both neutrophils and B-cells. With the exception of IL-17 mRNA, which was
      elevated in both control immunized and Mi-GFAP-IL6 cerebellum, the level of other
      cytokine and chemokine mRNAs were comparable with Mi-WT cerebellum whereas
      significantly higher levels of IFN-gamma and TNF-alpha mRNA were found in Mi-WT
      spinal cord. Thus, site-specific production of IL-6 in the cerebellum redirects
      trafficking away from the normally preferred antigenic site the spinal cord and
      acts as a leukocyte "sink" that markedly enhances the inflammatory cell
      accumulation and disease. The mechanisms underlying this process likely include
      the induction of specific chemokines, activation of microglia, and activation and
      loss of integrity of the blood-brain barrier present in the cerebellum of the
      GFAP-IL6 mice before the induction of EAE.

PMID- 19597001
TI  - Glucocorticoids induce protein S-dependent phagocytosis of apoptotic neutrophils
      by human macrophages.
AB  - During resolution of an inflammatory response, recruited neutrophil granulocytes
      undergo apoptosis and are removed by tissue phagocytes before induction of
      secondary necrosis without provoking proinflammatory cytokine production and
      release. Promotion of physiological neutrophil clearance mechanisms may represent
      a viable therapeutic strategy for the treatment of inflammatory or autoimmune
      diseases in which removal of apoptotic cells is impaired. The mechanism
      underlying enhancement of macrophage capacity for phagocytosis of apoptotic cells
      by the powerful anti-inflammatory drugs of the glucocorticoid family has remained
      elusive. In this study, we report that human monocyte-derived macrophages
      cultured in the presence of dexamethasone exhibit augmented capacity for
      phagocytosis of membrane-intact, early apoptotic cells only in the presence of a
      serum factor. Our results eliminate a role for a number of potential opsonins,
      including complement, pentraxin-3, and fibronectin. Using ion-exchange and gel
      filtration chromatography, we identified a high molecular mass serum fraction
      containing C4-binding protein and protein S responsible for the augmentation of
      phagocytosis of apoptotic neutrophils. Because the apoptotic neutrophils used in
      this study specifically bind protein S, we suggest that glucocorticoid treatment
      of macrophages induces a switch to a protein S-dependent apoptotic cell
      recognition mechanism. Consistent with this suggestion, pretreatment of
      macrophages with Abs to Mer tyrosine kinase, a member of the Tyro3/Axl/Mer family
      of receptor tyrosine kinases, prevented glucocorticoid augmentation of
      phagocytosis. Induction of a protein S/Mer tyrosine kinase-dependent apoptotic
      cell clearance pathway may contribute to the potent anti-inflammatory effects of
      glucocorticoids, representing a potential target for promoting resolution of
      inflammatory responses.

PMID- 19597002
TI  - Effects of low-dose aspirin on acute inflammatory responses in humans.
AB  - Aspirin is a unique nonsteroidal anti-inflammatory drug; at high doses
      (aspirin(high), 1g), it is anti-inflammatory stemming from the inhibition of
      cyclooxygenase and proinflammatory signaling pathways including NF-kappaB, but is
      cardioprotective at lower doses (aspirin(low), 75 mg). The latter arises from the
      inhibition of thromboxane (Tx) B(2), a prothrombotic eicosanoid also implicated
      in polymorphonuclear leukocyte trafficking. As a result, aspirin(low) is widely
      used as a primary and secondary preventative against vascular disease. Despite
      this and its ability to synthesize proresolution 15-epi-lipoxin A(4) it is not
      known whether aspirin(low) is anti-inflammatory in humans. To address this, we
      generated skin blisters by topically applying cantharidin on the forearm of
      healthy male volunteers, causing an acute inflammatory response including dermal
      edema formation and leukocyte trafficking. Although not affecting blister fluid
      volume, aspirin(low) (75 mg, oral, once daily/10 days) reduced polymorphonuclear
      leukocyte and macrophage accumulation independent of NF-kappaB-regulated gene
      expression and inhibition of conventional prostanoids. However, aspirin(low)
      triggered 15-epi-lipoxin A(4) synthesis and up-regulated its receptor (FPRL1,
      ALX). From complimentary in vitro experiments, we propose that 15-epi-lipoxin
      A(4) exerts its protective effects by triggering antiadhesive NO, thereby
      dampening leukocyte/endothelial cell interaction and subsequent extravascular
      leukocyte migration. Since similar findings were obtained from murine zymosan
      induced peritonitis, we suggest that aspirin(low) possesses the ability to
      inhibit mammalian innate immune-mediated responses. This highlights 15-epi
      lipoxin A(4) as a novel anti-inflammatory working through a defined receptor and
      suggests that mimicking its mode of action represents a new approach to treating
      inflammation-driven diseases.

PMID- 19597003
TI  - Obstacles to the successful development of an efficacious T cell-inducing HIV-1
      vaccine.
AB  - An efficacious vaccine to HIV-1 is direly needed to stem the global pandemic.
      Immunogens that elicit broadly cross-neutralizing antibodies to HIV-1 remain
      elusive, and thus, most HIV-1 vaccine efforts are focusing on induction of T
      cells. The notion that T cells can mediate protection against HIV-1 has been
      called into question by the failure of the STEP trial, which was designed to test
      this concept by the use of an E1-deleted Ad vaccine carrier. Lack of efficacy of
      the STEP trial vaccine underscores our limited knowledge about correlates of
      immune protection against HIV-1 and stresses the need for an enhanced commitment
      to basic research, including preclinical and clinical vaccine studies. In this
      review, we discuss known correlates of protection against HIV-1 and different
      vaccine strategies that have been or are being explored to induce such
      correlates, focusing on T cell-inducing vaccines and particularly on Ad vectors.

PMID- 19597004
TI  - Effect of dietary selenium and cigarette smoke on pulmonary cell proliferation in
      mice.
AB  - The objective of this study was to determine if dietary selenium could inhibit
      pulmonary cell proliferation in control and cigarette smoke-exposed female A/J
      mice. Selenium in the form of sodium selenite was supplemented to purified diets
      similar to the AIN-93M diet to yield 0.15, 0.5, or 2.0 mg selenium/kg diet. After
      3 weeks, mice in each dietary group were divided into two subgroups; one used as
      control, whereas the other was exposed to cigarette smoke for five consecutive
      days. Mice from both groups were euthanized 3 days later. Mice were administered
      bromodeoxyuridine in the drinking water starting 5 days before the initiation of
      the smoke exposure and continuing until they were euthanized. After euthanasia,
      the left lung lobe was processed for histology and cell proliferation analysis.
      Cigarette smoke increased cell proliferation in the terminal bronchioles and
      large airways, but not in alveoli. High-selenium diets inhibited cell
      proliferation in the alveoli, terminal bronchioles and large airways areas in
      both control and smoke-exposed mice. Increasing the dietary selenium level led to
      increased selenium levels in the blood and lung, and increased glutathione
      peroxidase (GPx) activity in the lung. Cytochrome P-450 1A1 protein levels in the
      lung were increased by cigarette smoke but were not affected by dietary selenium.
      It is concluded that dietary selenium inhibits pulmonary cell proliferation in
      both control and cigarette smoke-exposed mice, indicating that selenium is
      inhibiting cell proliferation independently of smoke exposure, and that this
      inhibition may be related to selenium concentration and GPx activity in the lung.

PMID- 19597005
TI  - Antibiotic treatment of animals infected with Borrelia burgdorferi.
AB  - Despite resolution of the objective manifestations of Lyme disease after
      antibiotic treatment, a minority of patients have fatigue, musculoskeletal pain,
      and/or difficulties with concentration or short-term memory of uncertain
      etiology; these are called post-Lyme disease symptoms or, in more severe cases,
      post-Lyme disease syndrome or "chronic Lyme disease." Several recent studies in
      which Borrelia burgdorferi-infected animals were treated with antibiotic therapy
      have demonstrated the presence of PCR positivity for B. burgdorferi DNA in the
      absence of culture positivity. In mice that were treated with antibiotic therapy,
      residual spirochetes could be taken up by ticks during a blood meal and could be
      transmitted to SCID mice. These spirochetes are attenuated; their presence is not
      associated with either inflammation or disease. In this review the methodology
      and findings of these studies are critically analyzed, and the significance of
      the results with regard to human Lyme disease is evaluated, with special emphasis
      on whether these studies provide useful insights into post-Lyme disease syndrome.
      A serious methodological concern is the failure to consider the pharmacokinetic
      pharmacodynamic properties of the antibiotic in choosing the dosage regimen used.
      We conclude that there is no scientific evidence to support the hypothesis that
      such spirochetes, should they exist in humans, are the cause of post-Lyme disease
      syndrome.

PMID- 19597006
TI  - Pathogenesis, diagnosis, and management of primary antibody deficiencies and
      infections.
AB  - Primary antibody deficiencies are the most common primary immunodeficiency
      diseases. They are a heterogeneous group of disorders with various degrees of
      dysfunctional antibody production resulting from a disruption of B-cell
      differentiation at different stages. While there has been tremendous recent
      progress in the understanding of some of these disorders, the etiology remains
      unknown for the majority of patients. As there is a large spectrum of underlying
      defects, the age at presentation varies widely, and the clinical manifestations
      range from an almost complete absence of B cells and serum immunoglobulins to
      selectively impaired antibody responses to specific antigens with normal total
      serum immunoglobulin concentrations. However, all of these disorders share an
      increased susceptibility to infections, affecting predominantly the respiratory
      tract. A delay of appropriate treatment for some diseases can result in serious
      complications related to infections, while timely diagnosis and adequate therapy
      can significantly decrease morbidity and increase life expectancy and quality of
      life.

PMID- 19597007
TI  - North American paragonimiasis (Caused by Paragonimus kellicotti) in the context
      of global paragonimiasis.
AB  - Paragonimus species are highly evolved parasites with a complex life cycle that
      involves at least three different hosts, i.e., snails, crustaceans, and mammals.
      The adult forms of Paragonimus species reside and mate in the lungs of a variety
      of permissive mammalian hosts, including humans. Although human paragonimiasis is
      uncommonly encountered in North America, both autochthonous and imported disease
      may be encountered. Paragonimus kellicotti, the species endemic to North America,
      is a well-known pathogen in wild and domestic animals. Five patients with North
      American paragonimiasis have been reported in the recent medical literature. The
      biologic, clinical, radiologic, and laboratory features of paragonimiasis are
      reviewed, with emphasis on North American paragonimiasis whenever possible.

PMID- 19597009
TI  - Food-borne trematodiases.
AB  - An estimated 750 million people are at risk of infections with food-borne
      trematodes, which comprise liver flukes (Clonorchis sinensis, Fasciola gigantica,
      Fasciola hepatica, Opisthorchis felineus, and Opisthorchis viverrini), lung
      flukes (Paragonimus spp.), and intestinal flukes (e.g., Echinostoma spp.,
      Fasciolopsis buski, and the heterophyids). Food-borne trematodiases pose a
      significant public health and economic problem, yet these diseases are often
      neglected. In this review, we summarize the taxonomy, morphology, and life cycle
      of food-borne trematodes. Estimates of the at-risk population and number of
      infections, geographic distribution, history, and ecological features of the
      major food-borne trematodes are reviewed. We summarize clinical manifestations,
      patterns of infection, and current means of diagnosis, treatment, and other
      control options. The changing epidemiological pattern and the rapid growth of
      aquaculture and food distribution networks are highlighted, as these developments
      might be associated with an elevated risk of transmission of food-borne
      trematodiases. Current research needs are emphasized.

PMID- 19597010
TI  - Gnathostomiasis, another emerging imported disease.
AB  - Gnathostomiasis is a food-borne zoonosis caused by the late-third stage larvae of
      Gnathostoma spp. It is being seen with increasing frequency in countries where it
      is not endemic and should be regarded as another emerging imported disease.
      Previously, its foci of endemicity have been confined to Southeast Asia and
      Central and South America, but its geographical boundaries appear to be
      increasing, with recent reports of infection in tourists returning from southern
      Africa. It has a complex life cycle involving at least two intermediate hosts,
      with humans being accidental hosts in which the larvae cannot reach sexual
      maturity. The main risks for acquisition are consumption of raw or undercooked
      freshwater fish and geographical exposure. Infection results in initial
      nonspecific symptoms followed by cutaneous and/or visceral larva migrans, with
      the latter carrying high morbidity and mortality rates if there is central
      nervous system involvement. We review the literature and describe the
      epidemiology, life cycle, clinical features, diagnosis, treatment, and prevention
      of gnathostomiasis.

PMID- 19597008
TI  - Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis.
AB  - Aspergillus species are globally ubiquitous saprophytes found in a variety of
      ecological niches. Almost 200 species of aspergilli have been identified, less
      than 20 of which are known to cause human disease. Among them, Aspergillus
      fumigatus is the most prevalent and is largely responsible for the increased
      incidence of invasive aspergillosis (IA) in the immunocompromised patient
      population. IA is a devastating illness, with mortality rates in some patient
      groups reaching as high as 90%. Studies identifying and assessing the roles of
      specific factors of A. fumigatus that contribute to the pathogenesis of IA have
      traditionally focused on single-gene deletion and mutant characterization. In
      combination with recent large-scale approaches analyzing global fungal responses
      to distinct environmental or host conditions, these studies have identified many
      factors that contribute to the overall pathogenic potential of A. fumigatus.
      Here, we provide an overview of the significant findings regarding A. fumigatus
      pathogenesis as it pertains to invasive disease.

PMID- 19597011
TI  - Advances and failures in preventing perinatal human immunodeficiency virus
      infection.
AB  - An estimated 2.5 million children are currently living with HIV, the vast
      majority as a result of mother-to-child transmission. Prevention of perinatal HIV
      infection has been immensely successful in developed countries. A comprehensive
      package of services, including maternal and infant antiretroviral therapy,
      elective cesarean section, and avoidance of breast-feeding, has resulted in
      transmission rates of less than 2%. However, in developing countries, access to
      such services is often not available, as demonstrated by the fact that the vast
      majority of children with HIV live in Africa. Over the past few years, many
      developing nations have made great strides in improving access to much-needed
      services. Notably, in eastern and southern Africa, the regions most affected by
      HIV, mother-to-child-transmission coverage rates for HIV-positive women increased
      from 11% in 2004 to 31% in 2006. These successes are deserving of recognition,
      while not losing sight of the fact that much remains to be done; currently, an
      estimated 75% of pregnant women worldwide have an unmet need for antiretroviral
      therapy. Further work is needed to determine the optimal strategy for reducing
      perinatal transmission among women in resource-poor settings, with a particular
      need for reduction of transmission via breast-feeding.

PMID- 19597013
TI  - Immortal person-time in studies of cancer outcomes.

PMID- 19597015
TI  - Induction chemotherapy in head and neck cancer.

PMID- 19597016
TI  - Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib.

PMID- 19597017
TI  - Ma-2 paraneoplastic encephalitis in the presence of bilateral testicular cancer:
      diagnostic and therapeutic approach.

PMID- 19597012
TI  - Resistance to therapies for infection by Plasmodium vivax.
AB  - The gravity of the threat posed by vivax malaria to public health has been poorly
      appreciated. The widely held misperception of Plasmodium vivax as being
      relatively infrequent, benign, and easily treated explains its nearly complete
      neglect across the range of biological and clinical research. Recent evidence
      suggests a far higher and more-severe disease burden imposed by increasingly drug
      resistant parasites. The two frontline therapies against vivax malaria,
      chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous
      use of these drugs, their respective mechanisms of activity, resistance, and
      toxicity remain unknown. Although standardized means of assessing therapeutic
      efficacy against blood and liver stages have not been developed, this review
      examines the provisional in vivo, ex vivo, and animal model systems for doing so.
      The rationale, design, and interpretation of clinical trials of therapies for
      vivax malaria are discussed in the context of the nuance and ambiguity imposed by
      the hypnozoite. Fielding new drug therapies against real-world vivax malaria may
      require a reworking of the strategic framework of drug development, namely, the
      conception, testing, and evaluation of sets of drugs designed for the cure of
      both blood and liver asexual stages as well as the sexual blood stages within a
      single therapeutic regimen.

PMID- 19597020
TI  - Surrogate response biomarkers in prevention research: do they point the way or
      lead us astray?

PMID- 19597019
TI  - Genetic basis of bilateral renal cancer: implications for evaluation and
      management.

PMID- 19597021
TI  - Merkel cell carcinoma: recent progress and current priorities on etiology,
      pathogenesis, and clinical management.
AB  - PURPOSE: To expedite improved understanding, diagnosis, treatment, and prevention
      of Merkel cell carcinoma (MCC), a rare malignancy of cutaneous neuroendocrine
      cells that has a 28% 2-year mortality rate. METHODS: This article summarizes a
      workshop that discussed the state-of-the-art research and priorities for research
      on MCC and on a new human polyomavirus (ie, MCPyV) recently discovered in 80% of
      MCC tumors. RESULTS: Normal Merkel cells are widely distributed in the epidermis
      near the end of nerve axons and may function as mechanoreceptors or
      chemoreceptors. Malignant MCC cells typically stain for cytokeratin 20 as well as
      for other epithelial and neuroendocrine markers. MCC subtypes, which are based on
      histology, on cell line growth properties, and on gene expression profiles, have
      been reported but have not been linked to prognosis. Clinical management has been
      empiric. MCPyV is clonally integrated at various sites in the human genome of MCC
      tumors, with truncating mutations in the viral, large T antigen gene that
      interrupt viral replication. MCPyV seroprevalence may be high, as with previously
      known human polyomaviruses. MCC risk is increased 11-fold with AIDS and with
      other cell-mediated immune deficiencies, B-cell neoplasms, and ultraviolet
      radiation exposure. CONCLUSION: Development and validation of a range
      quantitative polymerase chain reaction and serologic assays for detection of
      MCPyV, as well as an infectious clone of the virus, would clarify the fundamental
      biology, natural history, and epidemiology of the virus, of MCC, and of other
      diseases. Contingent on standardized histologic diagnosis and staging of MCC,
      consortia are needed to clarify the risks and benefits of sentinel lymph node
      biopsy, adjuvant radiation therapy, and salvage therapies; consortia are needed
      also for epidemiologic studies of MCC etiology.

PMID- 19597022
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors and depression.

PMID- 19597024
TI  - The forgotten spouse.

PMID- 19597023
TI  - Clinical trial designs for predictive biomarker validation: theoretical
      considerations and practical challenges.
AB  - PURPOSE: Biomarkers can add substantial value to current medical practice by
      providing an integrated approach to prediction using the genetic makeup of the
      tumor and the genotype of the patient to guide patient-specific treatment
      selection. We discuss and evaluate various clinical trial designs for the
      validation of biomarker-guided therapy. METHODS: Designs for predictive marker
      validation are broadly classified as retrospective (ie, using data from
      previously well-conducted randomized controlled trials [RCTs]) versus prospective
      (enrichment, unselected, hybrid, or adaptive analysis). We discuss the salient
      features of each design in the context of real trials. RESULTS: Well-designed
      retrospective analysis from well-conducted prospective RCTs can bring forward
      effective treatments to marker-defined subgroups of patients in a timely manner
      (eg, KRAS and colorectal cancer). Enrichment designs are appropriate when
      preliminary evidence suggest that patients with or without that marker profile do
      not benefit from the treatments in question; however, this may sometimes leave
      questions unanswered (eg, trastuzumab and breast cancer). An unselected design is
      optimal where preliminary evidence regarding treatment benefit and assay
      reproducibility is uncertain (eg, epidermal growth factor receptor and lung
      cancer). Hybrid designs are appropriate when preliminary evidence demonstrate the
      efficacy of certain treatments for a marker-defined subgroup, making it unethical
      to randomly assign patients with that marker status to other treatments (eg,
      multigene assay and breast cancer). Adaptive analysis designs allow for
      prespecified marker-defined subgroup analyses of data from an RCT. CONCLUSION:
      The implementation of these design strategies will lead to a more rapid clinical
      validation of biomarker-guided therapy.

PMID- 19597025
TI  - Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia:
      clinical results and prognostic marker analyses from the CLL2H study of the
      German Chronic Lymphocytic Leukemia Study Group.
AB  - PURPOSE: The phase II CLL2H trial evaluated safety and efficacy of subcutaneous
      alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia
      (CLL). Clinical and biologic markers were evaluated for their impacts on outcome.
      PATIENTS AND METHODS: One hundred nine patients were enrolled, and 103 received
      at least one dose of alemtuzumab. After dose escalation, alemtuzumab was
      administered subcutaneously at 30 mg three times weekly for up to 12 weeks.
      Response was assessed every 4 weeks during treatment and quarterly thereafter.
      RESULTS: The overall response rate was 34% (complete response, 4%; partial
      response, 30%). The median progression-free survival was 7.7 months, and the
      median overall survival (OS) was 19.1 months. Grades 3 to 4 neutropenia,
      thrombocytopenia, and anemia occurred in 56%, 57%, and 49% of patients,
      respectively. Grades 3 to 4 noncytomegalovirus and cytomegalovirus infections
      occurred in 29% and 8% of patients, respectively. Injection-site skin reactions
      were generally mild. Efficacy did not vary significantly in subgroups defined by
      genetic parameters (in particular, in 17p deletion, 11q deletion, mutated TP53,
      and unmutated VH), but efficacy was inferior in patients with increased beta2
      microglobulin (beta2-MG) and thymidine kinase (TK). In multivariate analysis of
      clinical and biologic variables, age, performance status, beta2-MG, and TK were
      independent prognostic factors for OS. CONCLUSION: Subcutaneous alemtuzumab
      appears as effective and safe as intravenous alemtuzumab in fludarabine
      refractory CLL. Subcutaneous administration should be the preferred delivery
      route because of its efficacy, convenience, improved adverse effect profile, and
      cost savings. In contrast to chemotherapy-based therapy, alemtuzumab treatment
      overcomes the adverse prognostic impact of VH mutation status, TP53 mutation, and
      genomic aberrations.

PMID- 19597026
TI  - Index to predict invasive mold infection in high-risk neutropenic patients based
      on the area over the neutrophil curve.
AB  - PURPOSE: Patients with prolonged and profound neutropenia are at high risk to
      develop invasive mold infections (IMIs). We developed an index (D-index) that
      combines duration and severity of neutropenia. The aim of this study was to test
      the D-index as a predictor of IMI. PATIENTS AND METHODS: The D-index was based on
      a graph plotting the absolute neutrophil counts during neutropenia and was the
      area over the neutrophil curve. We tested the D-index in 11 patients with acute
      myeloid leukemia (AML) who developed IMI during neutropenia and 33 AML patients
      without IMI (controls). We also calculated a cumulative D-index (c-D-index),
      defined as the cumulative D-index from the start of neutropenia until the date of
      the first clinical manifestation of IMI in patient cases. We compared the D-index
      and c-D-index with duration of neutropenia and defined a cutoff for IMI using the
      receiver operating characteristic (ROC) curve. RESULTS: The median duration of
      neutropenia and profound neutropenia of patient cases were significantly higher
      compared with controls (P = .002 and P = .001, respectively), as were the D-index
      (P < .001) and c-D-index (P = .02). The D-index and c-D-index performed better
      than duration of neutropenia in ROC curve analysis. For a cutoff point of 5,800
      of the c-D-index, the sensitivity and specificity were 91% and 58%, respectively,
      and for a prevalence of IMI of 5%, 10%, and 15%, the negative predictive values
      were 99%, 98%, and 97%, respectively. CONCLUSION: The high negative predictive
      value of the c-D-index may be of help in defining different risks for IMI in
      febrile neutropenic patients.

PMID- 19597027
TI  - Efficacy and safety of axitinib in patients with advanced non-small-cell lung
      cancer: results from a phase II study.
AB  - PURPOSE: This phase II study evaluated efficacy and safety of single-agent
      axitinib, an oral, potent, selective inhibitor of vascular endothelial growth
      factor receptors (VEGFR) -1, -2, and -3, in patients with advanced non-small-cell
      lung cancer (NSCLC). PATIENTS AND METHODS: This was an open-label, single-arm,
      multicenter, phase II study with a Simon two-stage minimax design. Patients
      received a starting dose of axitinib 5 mg orally BID. The primary end point was
      Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response
      rate. Secondary end points included safety and tolerability, overall survival
      (OS), and progression-free survival (PFS). RESULTS: Thirty-two patients were
      enrolled, with a median age of 66.5 years. The majority of patients (75%) had
      adenocarcinoma. Nine patients (28%) had received no prior chemotherapy for
      metastatic disease, and 23 (72%) had received > or = one regimen. Three patients
      (9%) had a RECIST investigator-assessed, confirmed partial response (PR); disease
      control rate (PR + stable disease) was 41%. Median PFS was 4.9 months overall
      (95% CI, 3.6 to 7.0 months). Median OS was 14.8 months (95% CI, 10.7 months to
      not estimable) overall and 14.8 months (95% CI, 12.5 months to not estimable) in
      patients receiving first-line axitinib. One-year survival rates for patients with
      or without prior therapy for metastatic disease were 57% and 78%, respectively.
      Grade 3 treatment-related adverse events in > or = 5% of patients comprised
      fatigue (22%), hypertension (9%), and hyponatremia (9%). CONCLUSION: Axitinib
      demonstrated single-agent activity in patients with advanced NSCLC. Therapy was
      well tolerated with manageable toxicities. Further investigation of this VEGFR
      inhibitor in NSCLC is of interest.

PMID- 19597028
TI  - Risk of bilateral renal cell cancer.
AB  - PURPOSE: The risk of developing bilateral kidney cancer has not been adequately
      defined in any large, population-based study with long-term follow-up to our
      knowledge. PATIENTS AND METHODS: We estimated the risk of metachronous bilateral
      renal cell cancer in patients diagnosed with unilateral kidney cancer, as
      recorded in the nationwide cancer registries of Norway and Sweden. Altogether
      28,642 patients were followed for an average of 4.4 years. The standardized
      incidence ratio--the ratio of the observed number of bilateral cancers to the
      number expected on the basis of the incidence in the Norwegian and Swedish
      population at large--was used as a measure of relative risk. We used multivariate
      Poisson regression to separate the effects of the explanatory variables. RESULTS:
      A synchronous bilateral renal cell cancer was reported in 86 patients. A total of
      112 metachronous bilateral cancers were recorded during 126,493 person-years of
      follow-up compared with 35.8 expected, yielding an overall relative risk (RR) of
      3.1 (95% CI, 2.6 to 3.8) and a cumulative incidence of 0.8% after 20 or more
      years of follow-up. In the multivariate analyses, risk increased monotonically
      with younger age at first diagnosis (P for trend < .001); compared with patients
      who were 60 years or older, those younger than 40 years were at a 17-fold higher
      risk (RR = 17.4; 95% CI, 10.1 to 29.8). We also found a modest but statistically
      significant decreasing trend with increasing duration of follow-up. CONCLUSION:
      The risk of metachronous bilateral renal cell cancer is drastically higher among
      patients first affected at a young age, suggesting a subset of early onset renal
      cell cancer with a strong genetic component.

PMID- 19597029
TI  - Risk of death from prostate cancer after brachytherapy alone or with radiation,
      androgen suppression therapy, or both in men with high-risk disease.
AB  - PURPOSE: We estimated the risk of prostate cancer (PC) -specific mortality (PCSM)
      after brachytherapy alone or in conjunction with androgen suppression therapy
      (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC.
      PATIENTS AND METHODS: The study cohort comprised 1,342 men with a prostate
      specific antigen level more than 20 ng/mL and clinical T3 or 4 and/or Gleason
      score 8 to 10 disease. Competing risks multivariable regression was performed to
      estimate the risk of PCSM in men treated with brachytherapy alone or with
      supplemental AST, EBRT, or both, adjusting for age, year of treatment, and known
      PC prognostic factors. RESULTS: Despite higher baseline probabilities of PCSM
      after a median follow-up of 5.1 years, there was a significant reduction in the
      risk of PCSM (adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006)
      in men treated with brachytherapy and both AST and EBRT as compared with neither.
      When compared with brachytherapy alone, a significant decrease in the risk of
      PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95%
      CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26).
      There was a near-significant reduction (AHR, 0.53; 95% CI, 0.27 to 1.07; P =
      .079) in the risk of PCSM in men treated with tri- as compared with bimodality
      therapy. CONCLUSION: Supplemental AST and EBRT but not either supplement compared
      with brachytherapy alone was associated with a decreased risk of PCSM in men with
      high-risk PC.

PMID- 19597030
TI  - Higher incidence of relapse with peripheral blood rather than marrow as a source
      of stem cells in adults with acute myelocytic leukemia autografted during the
      first remission.
AB  - PURPOSE: The cell source for autologous stem cell transplantation has shifted
      from bone marrow (BM) to peripheral blood (PB). In acute myelocytic leukemia
      (AML), for patients who receive transplants during first complete remission
      (CR1), no prospective randomized study has compared relapse incidence (RI) to
      cell source. PATIENTS AND METHODS: We analyzed 2,165 patients who received
      autografts (1,607 PB and 558 BM) from 1994 to 2006 and were reported to the
      European Cooperative Group for Blood and Marrow Transplantation with complete
      research data. Relative to the time of CR1, PB transplants were performed earlier
      than BM transplants. Because a poorer outcome was associated with a shorter
      interval from CR1 to transplantation, patients were divided into three groups:
      BM, early PB (< or = 80 days after CR1), and late PB (> 80 days after CR1)
      transplantation. RESULTS: In a multivariate analysis adjusted for differences
      between groups and center, RI was higher with both early PB (56% +/- 3%; hazard
      ratio [HR], 1.45; 95% CI, 1.11 to 1.9; P = .006) and late PB transplantation (46%
      +/- 2%; HR, 1.3; 95% CI, 1.06 to 1.59; P = .01) as compared with BM
      transplantation (39% +/- 2%). This translated into a significantly worse leukemia
      free survival (LFS) for early PB transplantation (36% +/- 3%; HR, 0.75; 95% CI,
      0.58 to 0.96; P = .02) and a trend for a poorer LFS for late PB (46% +/- 2%; HR,
      0.84; 95% CI, 0.7 to 1.01; P = .06) as compared with BM (52% +/- 2%). CONCLUSION:
      For patients with AML in CR1, risk of relapse is greater with PB transplantation
      rather than BM, independent of the interval from CR1 to transplantation.

PMID- 19597032
TI  - Introduction to the seventh international workshop on structure and function of
      the vascular system.

PMID- 19597031
TI  - Randomized double-blind 2 x 2 trial of low-dose tamoxifen and fenretinide for
      breast cancer prevention in high-risk premenopausal women.
AB  - PURPOSE: Tamoxifen and fenretinide are active in reducing premenopausal breast
      cancer risk and work synergistically in preclinical models. The authors assessed
      their combination in a two-by-two biomarker trial. PATIENTS AND METHODS: A total
      of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or
      intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk > or = 1.3% (n =
      54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d,
      their combination, or placebo. We report data for plasma insulin-like growth
      factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic
      events after 5.5 years. RESULTS: During the 2-year intervention, tamoxifen
      significantly lowered IGF-I and mammographic density by 12% and 20%,
      respectively, fenretinide by 4% and 10% (not significantly), their combination by
      20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased
      endometrial thickness principally in women becoming postmenopausal, whereas
      fenretinide decreased endometrial thickness significantly. The annual rate of
      breast neoplasms (n = 48) was 3.5% +/- 1.0%, 2.1% +/- 0.8%, 4.7% +/- 1.3%, and
      5.2% +/- 1.3% in the tamoxifen, fenretinide, combination, and placebo arms,
      respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95%
      CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen
      x fenretinide adverse interaction P = .03). There was no clear association with
      tumor receptor type. Baseline IGF-I and mammographic density did not predict
      breast neoplastic events, nor did change in mammographic density. CONCLUSION:
      Despite favorable effects on plasma IGF-I levels and mammographic density, the
      combination of low-dose tamoxifen plus fenretinide did not reduce breast
      neoplastic events compared to placebo, whereas both single agents, particularly
      fenretinide, showed numerical reduction in annual odds of breast neoplasms.
      Further follow-up is indicated.

PMID- 19597033
TI  - The cardioprotective effects of fish oil during pressure overload are blocked by
      high fat intake: role of cardiac phospholipid remodeling.
AB  - Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      from fish oil may prevent development of heart failure through alterations in
      cardiac phospholipids that favorably impact inflammation and energy metabolism. A
      high-fat diet may block these effects in chronically stressed myocardium.
      Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to
      pressure overload by constriction of the abdominal aorta. Animals were fed: (1)
      standard diet (10% of energy from fat), (2) standard diet with EPA+DHA (2.3% of
      energy intake as EPA+DHA), (3) high fat (60% fat); or (4) high fat with EPA+DHA.
      Pressure overload increased LV mass by approximately 40% in both standard and
      high-fat diets without fish oil. Supplementation with fish oil increased their
      incorporation into cardiac phospholipids, and decreased the proinflammatory fatty
      acid arachidonic acid and urine thromboxane B(2) with both the standard and high
      fat diet. Linoleic acid and tetralinoloyl cardiolipin (an essential mitochondrial
      phospholipid) were decreased with pressure overload on standard diet, which was
      prevented by fish oil. Animals fed high-fat diet had decreased linoleic acid and
      tetralinoloyl cardiolipin regardless of fish oil supplementation. Fish oil
      limited LV hypertrophy on the standard diet, and prevented upregulation of fetal
      genes associated with heart failure (myosin heavy chain-beta and atrial
      natriuetic factor). These beneficial effects of fish oil were absent in animals
      on the high-fat diet. In conclusion, whereas treatment with EPA+DHA prevented
      tetralinoloyl cardiolipin depletion, LV hypertrophy, and abnormal genes
      expression with pressure overload, these effects were absent with a high-fat
      diet.

PMID- 19597034
TI  - Is resveratrol the magic bullet for pulmonary hypertension?

PMID- 19597035
TI  - A risk score for risk factors: rationale and roadmap for preventing hypertension.

PMID- 19597036
TI  - [Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart:
      vasoactive mechanisms and inotropic action in disease.
AB  - Apelin receptors, present on vascular smooth muscle cells, endothelium, and
      cardiomyocytes, are activated by the family of apelin peptides to elicit
      cardiovascular effects in experimental animals, but functional activity in humans
      has not been studied in detail. We detected low levels of apelin immunoreactivity
      in plasma of volunteers consistent with an autocrine/paracrine action and
      detected apelin immunoreactivity in the supernatant from human cultured
      endothelial cells. We found that [Pyr(1)]apelin-13 was the predominant isoform in
      cardiac tissue from patients with coronary artery disease. We tested the
      hypothesis that apelins have vascular and cardiac actions in human tissues in
      vitro and compared responses to [Pyr(1)]apelin-13, apelin-13, and apelin-36. In
      endothelium-intact mammary artery, all 3 of the apelins induced concentration
      dependent vasodilatation with comparable potency (EC(50): 0.6 to 1.6 nM; maximum
      response: 40% to 50%). Vasodilatation was abolished after endothelial removal or
      preincubation with indomethacin but was unaffected by preincubation with N(G)
      nitro-L-arginine methyl ester, indicating involvement of prostanoids but not NO
      in dilatation by apelins in this patient group. Apelins were potent constrictors
      of endothelium-denuded saphenous vein (EC(50): 0.6 to 1.6 nM; maximum response:
      17% to 26%) and mammary artery ([Pyr(1)]apelin-13; EC(50): 0.2 nM; maximum
      response: 29%). In paced atrial strips, all 3 of the peptides increased the force
      of contraction with subnanomolar potencies (EC(50): 40 to 125 pM). For the first
      time, we demonstrate that the 3 principal forms of apelin have comparable potency
      and efficacy in human cardiovascular tissues. Apelins are potent endothelium
      dependent vasodilators acting via a prostanoid-dependent mechanism; however,
      removal of the endothelium revealed direct vasoconstrictor actions in both the
      artery and vein. Furthermore, in human cardiac tissue, the apelin peptides are
      among the most potent endogenous positive inotropic agents yet reported.

PMID- 19597037
TI  - Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor.
AB  - Recent advances in basic and clinical research have identified Rho kinase as an
      important target potentially implicated in a variety of cardiovascular diseases.
      Rho kinase is a downstream mediator of RhoA that leads to stress fiber formation,
      membrane ruffling, smooth muscle contraction, and cell motility. Increased Rho
      kinase activity is associated with vasoconstriction and elevated blood pressure.
      We identified a novel inhibitor of Rho kinase (SAR407899) and characterized its
      effects in biochemical, cellular, tissue-based, and in vivo assays. SAR407899 is
      an ATP-competitive Rho-kinase inhibitor, equipotent against human and rat-derived
      Rho-kinase 2 with inhibition constant values of 36 nM and 41 nM, respectively. It
      is highly selective in panel of 117 receptor and enzyme targets. SAR407899 is
      approximately 8-fold more active than fasudil. In vitro, SAR407899 demonstrated
      concentration-dependent inhibition of Rho-kinase-mediated phosphorylation of
      myosin phosphatase, thrombin-induced stress fiber formation, platelet-derived
      growth factor-induced proliferation, and monocyte chemotactic protein-1
      stimulated chemotaxis. SAR407899 potently (mean IC(50) values: 122 to 280 nM) and
      species-independently relaxed precontracted isolated arteries of different
      species and different vascular beds. In vivo, over the dose range 3 to 30 mg/kg
      PO, SAR407899 lowered blood pressure in a variety of rodent models of arterial
      hypertension. The antihypertensive effect of SAR407899 was superior to that of
      fasudil and Y-27632. In conclusion, SAR407899 is a novel and potent selective Rho
      kinase inhibitor with promising antihypertensive activity.

PMID- 19597038
TI  - Aliskiren enhances the protective effects of valsartan against cardiovascular and
      renal injury in endothelial nitric oxide synthase-deficient mice.
AB  - The protective effect of aliskiren, a direct renin inhibitor, against
      hypertensive cardiovascular and renal injury remains to be defined. This study
      was undertaken to examine the protective effects of the combination of aliskiren
      and valsartan, an angiotensin receptor blocker, against cardiovascular and renal
      injury. Endothelial NO synthase-deficient mice, subjected to cuff injury of
      femoral artery, were divided into 5 groups and were treated with the following:
      (1) vehicle; (2) aliskiren (25 mg/kg per day); (3) valsartan (8 mg/kg per day);
      (4) combined aliskiren (12.5 mg/kg per day) and valsartan (4 mg/kg per day); and
      (5) hydralazine (10 mg/kg per day) for 4 weeks. Aliskiren and valsartan alone
      markedly and similarly suppressed cardiac hypertrophy, inflammation and fibrosis,
      and coronary remodeling; prevented cuff injury-induced arterial intimal
      thickening; and reduced urinary albumin excretion, glomerular inflammation, and
      glomerulosclerosis in endothelial NO synthase-deficient mice. These beneficial
      effects of aliskiren and valsartan were associated with the significant
      attenuation of oxidative stress in these tissues. Hence, aliskiren and valsartan
      markedly exert the protective effects against cardiovascular and renal injury
      through the reduction of oxidative stress. Furthermore, compared with monotherapy
      with aliskiren or valsartan, the combination of a half dose of these drugs more
      greatly improved the above-mentioned cardiovascular and renal injuries of
      endothelial NO synthase-deficient mice, which were associated with greater
      attenuation of tissue oxidative stress by the combination therapy. Thus, the
      combination of aliskiren and valsartan exerts the synergistic organ-protective
      effects through synergistic attenuation of oxidative stress. The combination of
      aliskiren and valsartan seems to be a promising therapeutic strategy for
      hypertensive organ injury caused by endothelial NO synthase dysfunction.

PMID- 19597039
TI  - Tyrosine nitration of PA700 activates the 26S proteasome to induce endothelial
      dysfunction in mice with angiotensin II-induced hypertension.
AB  - The ubiquitin-proteasome system has been implicated in oxidative stress-induced
      endothelial dysfunction in cardiovascular diseases. However, the mechanism by
      which oxidative stress alters the ubiquitin-proteasome system is poorly defined.
      The present study was conducted to determine whether oxidative modifications of
      PA700, a 26S proteasome regulatory subunit, contributes to angiotensin II (Ang
      II)-induced endothelial dysfunction. Exposure of human umbilical vein endothelial
      cells to low concentrations of Ang II, but not vehicle, for 6 hours significantly
      decreased the levels of tetrahydro-l-biopterin (BH4), an essential cofactor of
      endothelial NO synthase, which was accompanied by a decrease in GTP
      cyclohydrolase I, the rate-limiting enzyme for de novo BH4 synthesis. In
      addition, Ang II increased both tyrosine nitration of PA700 and the 26S
      proteasome activity, which were paralleled by increased coimmunoprecipitation of
      PA700 and the 20S proteasome. Genetic inhibition of NAD(P)H oxidase or
      administration of uric acid (a peroxynitrite scavenger) or N(G)-nitro-l-arginine
      methyl ester (nonselective NO synthase inhibitor) significantly attenuated Ang II
      induced PA700 nitration, 26S proteasome activation, and reduction of GTP
      cyclohydrolase I and BH4. Finally, Ang II infusion in mice decreased the levels
      of both BH4 and GTP cyclohydrolase I and impaired endothelial-dependent
      relaxation in isolated aortas, and all of these effects were prevented by the
      administration of MG132, a potent inhibitor for 26S proteasome. We conclude that
      Ang II increases tyrosine nitration of PA700 resulting in accelerated GTP
      cyclohydrolase I degradation, BH4 deficiency, and consequent endothelial
      dysfunction in hypertension.

PMID- 19597040
TI  - Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats.
AB  - Proliferation of pulmonary arterial smooth muscle cells, endothelial dysfunction,
      oxidative stress, and inflammation promotes the development of pulmonary
      hypertension. Resveratrol is a polyphenolic compound that exerts antioxidant and
      anti-inflammatory protective effects in the systemic circulation, but its effects
      on pulmonary arteries remain poorly defined. The present study was undertaken to
      investigate the efficacy of resveratrol to prevent pulmonary hypertension. Rats
      injected with monocrotaline progressively developed pulmonary hypertension.
      Resveratrol treatment (25 mg/kg per day, PO, from day 1 postmonocrotaline)
      attenuated right ventricular systolic pressure and pulmonary arterial remodeling,
      decreased expression of inflammatory cytokines (tumor necrosis factor-alpha,
      interleukin 1beta, interleukin 6, and platelet-derived growth factor-alpha/beta),
      and limited leukocyte infiltration in the lung. Resveratrol also inhibited
      proliferation of pulmonary arterial smooth muscle cells. Treatment of rats with
      resveratrol increased expression of endothelial NO synthase, decreased oxidative
      stress, and improved endothelial function in small pulmonary arteries. Pulmonary
      hypertension was associated with an upregulation of NAD(P)H oxidase in small
      pulmonary arteries, which was significantly attenuated by resveratrol treatment.
      Our studies show that resveratrol exerts anti-inflammatory, antioxidant, and
      antiproliferative effects in the pulmonary arteries, which may contribute to the
      prevention of pulmonary hypertension.

PMID- 19597041
TI  - Validating the Framingham Hypertension Risk Score: results from the Whitehall II
      study.
AB  - A promising hypertension risk prediction score using data from the US Framingham
      Offspring Study has been developed, but this score has not been tested in other
      cohorts. We examined the predictive performance of the Framingham hypertension
      risk score in a European population, the Whitehall II Study. Participants were
      6704 London-based civil servants aged 35 to 68 years, 31% women, free from
      prevalent hypertension, diabetes mellitus, and coronary heart disease. Standard
      clinical examinations of blood pressure, weight and height, current cigarette
      smoking, and parental history of hypertension were undertaken every 5 years for a
      total of 4 times. We recorded a total of 2043 incident (new-onset) cases of
      hypertension in three 5-year baseline follow-up data cycles. Both discrimination
      (C statistic: 0.80) and calibration (Hosmer-Lemeshow chi(2): 11.5) of the
      Framingham hypertension risk score were good. Agreement between the predicted and
      observed hypertension incidences was excellent across the risk score
      distribution. The overall predicted:observed ratio was 1.08, slightly better
      among individuals >50 years of age (0.99 in men and 1.02 in women) than in
      younger participants (1.16 in men and 1.18 in women). Reclassification with a
      modified score on the basis of our study population did not improve the
      prediction (net reclassification improvement: -0.5%; 95% CI: -2.5% to 1.5%).
      These data suggest that the Framingham hypertension risk score provides a valid
      tool with which to estimate near-term risk of developing hypertension.

PMID- 19597043
TI  - Immunology in hypertension, preeclampsia, and target-organ damage.

PMID- 19597044
TI  - Mitral leaflet in functional regurgitation: passive bystander or active player?

PMID- 19597042
TI  - Blood pressure is a major risk factor for renal death: an analysis of 560 352
      participants from the Asia-Pacific region.
AB  - Chronic kidney disease is a major worldwide public health problem that causes
      substantial morbidity and mortality. Studies from the Asia-Pacific region have
      reported some of the highest chronic kidney disease prevalence rates in the
      world, but access to dialysis is limited in many countries, making it imperative
      to identify high-risk individuals. We performed a participant-level data overview
      of prospective studies conducted in the Asia-Pacific region to quantify the
      magnitude and direction of the associations between putative risk factors and
      renal death. Age- and sex-adjusted Cox proportional hazards models were applied
      to pooled data from 35 studies to calculate hazard ratios (95% CIs) for renal
      death associated with a standardized change in risk factors. Among 560 352
      participants followed for a median of 6.8 years, a total of 420 renal deaths were
      observed. Continuous and positive associations among systolic blood pressure,
      diastolic blood pressure, fasting blood glucose, and total cholesterol levels
      with renal death were observed, as well as a continuous but inverse association
      with high-density lipoprotein cholesterol. Systolic blood pressure was the
      strongest risk factor for renal death with each SD increase in systolic blood
      pressure (19 mm Hg) associated with >80% higher risk (hazard ratio: 1.84; 95% CI:
      1.60 to 2.12). Neither cigarette smoking nor excess weight was related to the
      risk of renal death (P>0.10). The results were similar for cohorts in Asia and
      Australia. These results suggest that primary prevention strategies for renal
      disease should focus on individuals with elevated blood pressure, diabetes
      mellitus, and dyslipidemia.

PMID- 19597045
TI  - Functional mitral regurgitation and transcatheter mitral annuloplasty: the
      Carillon Mitral Annuloplasty Device European Union Study in perspective.

PMID- 19597046
TI  - Heart malformation: what are the chances it could happen again?

PMID- 19597047
TI  - Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile
      dysfunction.
AB  - BACKGROUND: Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in
      insulin action and tumorigenesis. Myocyte contraction is initiated by an inward
      Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel
      (LTCC). The aim of this study was to evaluate whether p110alpha also controls
      cardiac contractility by regulating the LTCC. METHODS AND RESULTS: Genetic
      ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as
      Pik3cb), in cardiac myocytes of adult mice reduced I(Ca,L) and blocked insulin
      signaling in the heart. p110alpha-null myocytes had a reduced number of LTCCs on
      the cell surface and a contractile defect that decreased cardiac function in
      vivo. Similarly, pharmacological inhibition of p110alpha decreased I(Ca,L) and
      contractility in canine myocytes. Inhibition of p110beta did not reduce I(Ca,L).
      CONCLUSIONS: PI3K p110alpha but not p110beta regulates the LTCC in cardiac
      myocytes. Decreased signaling to p110alpha reduces the number of LTCCs on the
      cell surface and thus attenuates I(Ca,L) and contractility.

PMID- 19597048
TI  - Recurrence of congenital heart defects in families.
AB  - BACKGROUND: Knowledge of the familial contribution to congenital heart diseases
      (CHD) on an individual and population level is sparse. We estimated an
      individual's risk of CHD given a family history of CHD, as well as the
      contribution of CHD family history to the total number of CHD cases in the
      population. METHODS AND RESULTS: In a national cohort study, we linked all Danish
      residents to the National Patient Register, the Causes of Death Register, the
      Danish Central Cytogenetic Register, and the Danish Family Relations Database,
      yielding 1 763 591 persons born in Denmark between 1977 and 2005, of whom 18 708
      had CHD. Individuals with CHD were classified by phenotype. We estimated
      recurrence risk ratios and population-attributable risk. Among first-degree
      relatives, the recurrence risk ratio was 79.1 (95% confidence interval [CI] 32.9
      to 190) for heterotaxia, 11.7 (95% CI, 8.0 to 17.0) for conotruncal defects, 24.3
      (95% CI,12.2 to 48.7) for atrioventricular septal defect, 12.9 (95% CI, 7.48 to
      22.2) for left ventricular outflow tract obstruction, 48.6 (95% CI, 27.5 to 85.6)
      for right ventricular outflow tract obstruction, 7.1 (95% CI, 4.5 to 11.1) for
      isolated atrial septal defect, and 3.4 (95% CI, 2.2 to 5.3) for isolated
      ventricular septal defect. The overall recurrence risk ratio for the same defect
      was 8.15 (95% CI, 6.95 to 9.55), whereas it was 2.68 (95% CI, 2.43 to 2.97) for
      different heart defects. Only 2.2% of heart defect cases in the population (4.2%
      after the exclusion of chromosomal aberrations) were attributed to CHD family
      history in first-degree relatives. CONCLUSIONS: Specific CHDs showed highly
      variable but strong familial clustering in first-degree relatives, ranging from 3
      fold to 80-fold compared with the population prevalence, whereas the crossover
      risks between dissimilar cases of CHD were weaker. Family history of any CHD
      among first-degree relatives accounted for a small proportion of CHD cases in the
      population.

PMID- 19597050
TI  - Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest
      Survivors With Preserved Ejection Fraction Registry (CASPER).
AB  - BACKGROUND: Cardiac arrest without evident cardiac disease may be caused by
      subclinical genetic conditions. Provocative testing to unmask a phenotype is
      often necessary to detect primary electrical disease, direct genetic testing, and
      perform family screening. METHODS AND RESULTS: Patients with apparently
      unexplained cardiac arrest and no evident cardiac disease (normal cardiac
      function on echocardiogram, no evidence of coronary artery disease, and a normal
      ECG) underwent systematic evaluation that included cardiac magnetic resonance
      imaging, signal-averaged ECG, exercise testing, drug challenge, and selective
      electrophysiological testing. Diagnostic criteria were based on accepted criteria
      or provocation of the characteristic clinical features for long-QT syndrome,
      catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early
      repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm,
      and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0+/-13.4
      years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome
      in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic
      right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm
      in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing
      demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening
      of 64 family members of these patients identified 15 affected individuals who
      were treated (24%). The remaining 28 patients (44%) were considered to have
      idiopathic ventricular fibrillation. CONCLUSIONS: Systematic clinical testing,
      including drug provocation and advanced imaging, results in unmasking of the
      cause of apparently unexplained cardiac arrest in >50% of patients. This approach
      assists in directing genetic testing to diagnose genetically mediated arrhythmia
      syndromes, which results in successful family screening.

PMID- 19597049
TI  - Neuregulin-1 beta is associated with disease severity and adverse outcomes in
      chronic heart failure.
AB  - BACKGROUND: Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular
      endothelial cells that has cardioprotective effects in animal models of heart
      failure. However, circulating NRG-1 has not been studied in human heart disease.
      We used a novel immunoassay to test whether circulating NRG-1beta is associated
      with disease severity and clinical outcomes in chronic heart failure. METHODS AND
      RESULTS: Serum NRG-1beta was quantified in 899 outpatients in the Penn Heart
      Failure Study, a referral cohort representing a broad spectrum of systolic heart
      failure. Circulating NRG-1beta was significantly elevated in patients with worse
      disease severity (median, 6.2 ng/mL for New York Heart Association class IV
      versus 4.4 ng/mL for class I; P=0.002). In adjusted models, NRG-1beta was
      independently associated with an increased risk of death or cardiac
      transplantation over a median follow-up of 2.4 years (adjusted hazard ratio,
      1.58; 95% confidence interval, 1.04 to 2.39; P=0.03 comparing fourth versus first
      NRG-1beta quartile). Associations with outcome differed by heart failure cause
      and symptom severity, with the strongest associations observed in patients with
      ischemic cardiomyopathy (interaction P=0.008) and New York Heart Association
      class III/IV symptoms (interaction P=0.01). These findings were all independent
      of brain natriuretic peptide, and assessment of NRG-1beta and brain natriuretic
      peptide jointly provided better risk stratification than each biomarker
      individually in patients with ischemic or New York Heart Association class III/IV
      heart failure. CONCLUSIONS: Circulating NRG-1beta is independently associated
      with heart failure severity and risk of death or cardiac transplantation. These
      findings support a role for NRG-1/ErbB signaling in human heart failure and
      identify serum NRG-1beta as a novel biomarker that may have clinical
      applications.

PMID- 19597051
TI  - Percutaneous mitral annuloplasty for functional mitral regurgitation: results of
      the CARILLON Mitral Annuloplasty Device European Union Study.
AB  - BACKGROUND: Functional mitral regurgitation (FMR), a well-recognized component of
      left ventricular remodeling, is associated with increased morbidity and mortality
      in heart failure patients. Percutaneous mitral annuloplasty has the potential to
      serve as a therapeutic adjunct to standard medical care. METHODS AND RESULTS:
      Patients with dilated cardiomyopathy, moderate to severe FMR, an ejection
      fraction <40%, and a 6-minute walk distance between 150 and 450 m were enrolled
      in the CARILLON Mitral Annuloplasty Device European Union Study (AMADEUS).
      Percutaneous mitral annuloplasty was achieved through the coronary sinus with the
      CARILLON Mitral Contour System. Echocardiographic FMR grade, exercise tolerance,
      New York Heart Association class, and quality of life were assessed at baseline
      and 1 and 6 months. Of the 48 patients enrolled in the trial, 30 received the
      CARILLON device. Eighteen patients did not receive a device because of access
      issues, insufficient acute FMR reduction, or coronary artery compromise. The
      major adverse event rate was 13% at 30 days. At 6 months, the degree of FMR
      reduction among 5 different quantitative echocardiographic measures ranged from
      22% to 32%. Six-minute walk distance improved from 307+/-87 m at baseline to
      403+/-137 m at 6 months (P<0.001). Quality of life, measured by the Kansas City
      Cardiomyopathy Questionnaire, improved from 47+/-16 points at baseline to 69+/-15
      points at 6 months (P<0.001). CONCLUSIONS: Percutaneous reduction in FMR with a
      novel coronary sinus-based mitral annuloplasty device is feasible in patients
      with heart failure, is associated with a low rate of major adverse events, and is
      associated with improvement in quality of life and exercise tolerance.

PMID- 19597053
TI  - Children and adults with congenital heart disease lost to follow-up: who and
      when?
AB  - BACKGROUND: Many patients with congenital heart disease (CHD) require lifelong
      care. However, the duration of cardiology follow-up in children and adults with
      CHD is unknown. We sought to determine the proportion of children and young
      adults with CHD receiving outpatient cardiology care and to identify predictors
      of lack of follow-up. METHODS AND RESULTS: The study population consisted of
      individuals born in 1983 and alive at age 22 years who were diagnosed with CHD in
      Quebec, Canada, before 6 years of age (n=643). Patients and outpatient visits
      were identified with the use of the provincial physician's claims database. Three
      age groups were examined for the presence of outpatient cardiology follow-up: 6
      to 12, 13 to 17, and 18 to 22 years. CHD lesions were classified as severe (n=84;
      13%), simple shunts (n=390; 61%), and "other" lesions (n=169; 26%). Failure to
      receive cardiac follow-up after the 6th, 13th, and 18th birthday occurred in 28%,
      47%, and 61%, respectively. Among those with severe lesions, only 79% were seen
      after the 18th birthday. However, the majority of subjects visited primary care
      physicians in all age groups, and 93% remained in contact with the healthcare
      system into early adulthood. Predictors of lack of cardiology follow-up in
      adulthood included male sex, a nonsevere lesion, and a history of follow-up
      outside a university hospital setting. CONCLUSIONS: Lack of cardiology follow-up
      begins during childhood, even among those with severe lesions. This occurs
      despite patients being in contact with other healthcare providers. Improved
      communication with primary care physicians may reduce the proportion of patients
      lost to cardiac follow-up.

PMID- 19597052
TI  - Active adaptation of the tethered mitral valve: insights into a compensatory
      mechanism for functional mitral regurgitation.
AB  - BACKGROUND: In patients with left ventricular infarction or dilatation, leaflet
      tethering by displaced papillary muscles frequently induces mitral regurgitation,
      which doubles mortality. Little is known about the biological potential of the
      mitral valve (MV) to compensate for ventricular remodeling. We tested the
      hypothesis that MV leaflet surface area increases over time with mechanical
      stretch created by papillary muscle displacement through cell activation, not
      passive stretching. METHODS AND RESULTS: Under cardiopulmonary bypass, the
      papillary muscle tips in 6 adult sheep were retracted apically short of producing
      mitral regurgitation to replicate tethering without confounding myocardial
      infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional
      echocardiography over 61+/-6 days compared with 6 unstretched sheep MVs. Total
      diastolic leaflet area increased by 2.4+/-1.3 cm(2) (17+/-10%) from 14.3+/-1.9 to
      16.7+/-1.9 cm(2) (P=0.006) with stretch with no change in the unstretched valves
      despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal
      (1.18+/-0.14 versus 0.42+/-0.14 mm; P<0.0001) at 60 days with an increased
      spongiosa layer. Endothelial cells (CD31(+)) coexpressing alpha-smooth muscle
      actin were significantly more common by fluorescent cell sorting in tethered
      versus normal leaflets (41+/-19% versus 9+/-5%; P=0.02), indicating endothelial
      mesenchymal transdifferentiation. alpha-Smooth muscle actin-positive cells
      appeared in the atrial endothelium, penetrating into the interstitium, with
      increased collagen deposition. Thickened chordae showed endothelial and
      subendothelial alpha-smooth muscle actin. Endothelial-mesenchymal
      transdifferentiation capacity also was demonstrated in cultured MV endothelial
      cells. CONCLUSIONS: Mechanical stresses imposed by papillary muscle tethering
      increase MV leaflet area and thickness, with cellular changes suggesting
      reactivated embryonic developmental pathways. Understanding such actively
      adaptive mechanisms can potentially provide therapeutic opportunities to augment
      MV area and reduce ischemic mitral regurgitation.

PMID- 19597055
TI  - Spinal cord stimulation improves ventricular function and reduces ventricular
      arrhythmias in a canine postinfarction heart failure model.
AB  - BACKGROUND: Spinal cord stimulation (SCS) reduces the incidence of ventricular
      tachyarrhythmias in experimental models. This study investigated the effects of
      long-term SCS on ventricular function in a postinfarction canine heart failure
      model. METHODS AND RESULTS: In stage 1, dogs underwent implantable cardioverter
      defibrillator implantation and embolization of the left anterior descending
      artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce
      heart failure. In stage 2, 28 surviving animals were assigned to the SCS
      (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED;
      carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for
      the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors
      were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD),
      SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5
      weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent
      circumflex artery balloon occlusion for 1 hour. In the SCS group, left
      ventricular ejection fraction was 65+/-5% at baseline, 17+/-3% at the end of
      stage 1, and 47+/-7% at the end of stage 2. In the MED group, left ventricular
      ejection fraction was 61+/-4% at baseline, 18+/-3% at the end of stage 1, and
      34+/-4% at the end of stage 2. In the CTRL group, left ventricular ejection
      fraction was 64+/-5% at baseline, 19+/-5% at the end of stage 1, and 28+/-3% at
      the end of stage 2. Left ventricular ejection fraction was significantly improved
      in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean
      number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2
      and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also
      were significantly decreased in the SCS (27+/-17 and 27%, respectively; P<0.03)
      and MED (58+/-42 and 33%; P<0.05) versus CTRL (88+/-52 and 76%) group. After 10
      weeks in the phase 2 studies, the greatest recovery in ejection fraction was
      noted in the SCS (52+/-5%) and SCS+MEDS (46+/-4%) groups compared with the MEDS
      (38+/-2%) and CTRL (31+/-4%) groups. CONCLUSIONS: SCS significantly improved
      cardiac contractile function and decreased ventricular arrhythmias in canine
      heart failure.

PMID- 19597056
TI  - Suicide experiences among institutionalized older veterans in Taiwan.
AB  - PURPOSE: Institutionalized veterans in Taiwan are a high-risk group for
      completing suicide due to their institutionalization and social minority status.
      The purpose of this study was to understand the suicide experiences, especially
      the triggers of suicide in this group. DESIGN AND METHODS: Data about suicide
      experiences were collected from 19 older (> or =65 years) residents who had
      attempted suicide in four veterans' homes in Taiwan from 2006 to 2007.
      Transcripts from 26 tape-recorded interviews were analyzed by thematic analysis.
      RESULTS: Five major themes related to suicide triggers were identified: illness
      and pain, death of close relatives or friends, conflicts with family members,
      disputes with friends or workers, and difficulty adapting to institutional life.
      IMPLICATIONS: Illness and physical limitation issues were similar to suicidal
      findings on older people in Western culture. However, the suicidal behavior of
      these institutionalized, older Taiwanese veterans was influenced by expectations
      that did not match current social changes, money management issues, death of
      significant others, and changes in living environment. We suggest that money
      problems with paraprofessional institutional workers could be minimized among
      older institutionalized veterans by providing a convenient means for them to
      withdraw or manage money. Institutional staff should also be educated about
      communicating with older people and about death and dying; older residents should
      be educated about current social changes and money management. The study themes
      may be used to develop a new model for predicting suicide in this population and
      could be incorporated into current suicide prevention programs in clinical
      practice.

PMID- 19597057
TI  - Reforming long-term care in the United States: findings from a national survey of
      specialists.
AB  - PURPOSE: Theories of the policy process recognize that policy proposals are
      typically generated, debated, redrafted, and accepted for consideration through
      the gradual accumulation of knowledge within communities of specialists. Thus, to
      inform long-term care (LTC) reform efforts, we conducted a Web-based survey of
      1,147 LTC specialists nationwide. DESIGN AND METHODS: Survey respondents included
      consumer advocates, provider representatives, public officials, policy experts,
      and others with experience in LTC. Administration took place between September
      2007 and March 2008 and addressed prevailing challenges and options for reform.
      RESULTS: Although differences could be discerned, constituency group views
      converged in several areas. There was general agreement that LTC financing needed
      to be socialized more and that impediments to organizational change needed to be
      overcome. Respondents also felt that LTC needed to be rebalanced toward home- and
      community-based settings, though few supported doing so by limiting nursing home
      (NH) bed supply. Although virtually all felt that the federal government was
      doing a poor job regulating LTC providers, most believed that the approaches used
      to oversee NHs should also be applied to assisted living. Payment incentives were
      highlighted as the most effective strategy for improving quality even though it
      suffers from the same informational deficits compromising consumer reporting.
      IMPLICATIONS: By giving voice to those who know LTC very well, and identifying
      areas of agreement and disagreement, this study should prove useful in promoting
      LTC reform where it might otherwise remain politically intransigent.

PMID- 19597054
TI  - Alcohol consumption and risk of cardiovascular disease and death in women:
      potential mediating mechanisms.
AB  - BACKGROUND: Although an association between moderate alcohol consumption and
      decreased cardiovascular disease (CVD) and death has been reported, limited data
      are available on potential mediating mechanisms. We examined the association
      between alcohol and CVD and death in 26 399 women and estimated the proportion of
      reduced risk of CVD/death explained by a series of intermediate factors. METHODS
      AND RESULTS: Alcohol consumption was self-reported at baseline, and CVD events
      and deaths were ascertained via follow-up questionnaires and medical records.
      Baseline levels of hemoglobin A1c, inflammatory markers, hemostatic factors, and
      lipids were measured. Blood pressure and hypercholesterolemia and treatment for
      lipids were self-reported. During a mean follow up of 12.2 years, 1039 CVD events
      and 785 deaths (153 CVD deaths) occurred. There was a J-shaped relation between
      alcohol consumption and incident CVD and total and CVD deaths in a multivariable
      model. Compared with abstainers, alcohol intake of 5 to 14.9 g/d was associated
      with 26%, 35%, and 51% lower risk of CVD, total death, and CVD death,
      respectively, in a multivariable model. For CVD risk reduction, lipids made the
      largest contribution to the lower risk of CVD (28.7%), followed by hemoglobin
      A1c/diabetes (25.3%), inflammatory/hemostatic factors (5%), and blood pressure
      factors (4.6%). All these mediating factors together explained 86.3%, 18.7%, and
      21.8% of the observed lower risk of CVD, total death, and CVD death,
      respectively. CONCLUSIONS: These data suggest that alcohol effects on lipids and
      insulin sensitivity may account for a large proportion of the lower risk of
      CVD/death observed with moderate drinking under the assumption that the alcohol
      CVD association is causal.

PMID- 19597058
TI  - Primary care physicians' dementia care practices: evidence of geographic
      variation.
AB  - PURPOSE: This article explores primary care physicians' (PCPs) self-reported
      approaches and barriers to management of patients with dementia, with a focus on
      comparisons in dementia care practices between PCPs in 2 states. DESIGN AND
      METHODS: In this cross-sectional study, questionnaires were mailed to 600
      randomly selected licensed PCPs in Connecticut and to all 1,017 licensed PCPs in
      Maine. RESULTS: A total of 422 eligible PCPs responded. Nearly 90% of PCPs
      prescribed donepezil in the previous year for their dementia patients.
      Connecticut PCPs were more likely to prescribe several other therapeutics than
      their Maine counterparts. Connecticut PCPs were more likely to refer dementia
      patients to adult day care (85% vs. 59%) but less likely to refer to Area
      Agencies on Aging (21% vs. 44%; both ps < .05); referral rates to Alzheimer's
      Association chapters were low in both states (30%). A greater proportion of
      Connecticut PCPs reported barriers to optimal dementia care, including time
      constraints (54% vs. 31% of Maine PCPs), unfamiliarity with community resources
      (46% vs. 30%), and reimbursement constraints (45% vs. 23%; all ps <or= .05). Two
      thirds of PCPs were "very" or "somewhat" interested in using information
      technology to assist with dementia diagnosis and management; controlling for
      other variables, youngest PCPs were more than twice as likely as oldest to
      profess such interest (adjusted odds ratio = 2.04; 95% confidence interval [CI] =
      1.02-4.08). IMPLICATIONS: Geographic variations are evident in PCP medication
      prescription patterns, community resource referral patterns, and reported
      barriers to optimal dementia care. Younger PCPs are more likely to adopt
      information technology to assist in dementia diagnosis and management.

PMID- 19597059
TI  - Letter by Reeder and Anderson regarding article, "Heart failure is a risk factor
      for orthopedic fracture: a population-based analysis of 16 294 patients".

PMID- 19597060
TI  - Images in cardiovascular medicine. Live echocardiographic visualization of the
      migration of a voluminous left ventricular thrombus complicating an acute
      myocarditis.

PMID- 19597062
TI  - Adventures in cardiovascular research.
AB  - This article, derived from an invited Distinguished Scientist lecture presented
      at the American Heart Association Scientific Sessions in 2007, reviews 4 themes
      (adventures) in clinical cardiovascular research carried out over a period of 58
      years. It begins with the author's introduction to cardiovascular hemodynamics
      during a medical school elective in 1951. The 4 adventures include valvular heart
      disease, hypertrophic cardiomyopathy, heart failure (HF), and myocardial
      ischemia. In each of these adventures, the author describes briefly what was
      known when he entered each field, followed by the author's contribution to the
      field (the adventure), and ends with comments about the current status of the
      field. Of particular interest are the changes in the technologies used in
      clinical cardiovascular research over the past half century, commencing with
      pressure tracings in left heart chambers with the use of needle puncture in the
      operating room to genetic technologies designed to understand differences between
      drugs that inhibit platelet activation. The article ends with some general
      comments on conducting research and the rewards that can come with this activity.

PMID- 19597063
TI  - Images in cardiovascular medicine. Dynamic left main coronary artery obstruction
      associated with Williams syndrome.

PMID- 19597064
TI  - Multivitamin supplements, ageing, and loss of vision: seeing through the shadows.

PMID- 19597065
TI  - Channeling David E. Rogers, MD: the moral imperative for health care reform.

PMID- 19597066
TI  - Calcium scoring with computed tomography: what is the radiation risk?

PMID- 19597067
TI  - Coronary artery calcification screening: estimated radiation dose and cancer
      risk.
AB  - BACKGROUND: Multidetector computed tomography has been proposed as a tool for
      routine screening for coronary artery calcification in asymptomatic individuals.
      As proposed, such screening could involve tens of millions of individuals, but
      detailed estimates of radiation doses and potential risk of radiation-induced
      cancer are not currently available. We estimated organ-specific radiation doses
      and associated cancer risks from coronary artery calcification screening with
      multidetector computed tomography according to patient age, frequency of
      screening, and scan protocol. METHODS: Radiation doses delivered to adult
      patients were calculated from a range of available protocols using Monte Carlo
      radiation transport. Radiation risk models, derived using data from Japanese
      atomic bomb survivors and medically exposed cohorts, were used to estimate the
      excess lifetime risk of radiation-induced cancer. RESULTS: The radiation dose
      from a single coronary artery calcification computed tomographic scan varied more
      than 10-fold (effective dose range, 0.8-10.5 mSv) depending on the protocol. In
      general, higher radiation doses were associated with higher x-ray tube current,
      higher tube potential, spiral scanning with low pitch, and retrospective gating.
      The wide dose variation also resulted in wide variation in estimated radiation
      induced cancer risk. Assuming screening every 5 years from the age of 45 to 75
      years for men and 55 to 75 years for women, the estimated excess lifetime cancer
      risk using the median dose of 2.3 mSv was 42 cases per 100 000 men (range, 14-200
      cases) and 62 cases per 100 000 women (range, 21-300 cases). CONCLUSIONS: These
      radiation risk estimates can be compared with potential benefits from screening,
      when such estimates are available. Doses and therefore risks can be minimized by
      the use of optimized protocols.

PMID- 19597068
TI  - Angiotensin-converting enzyme inhibitors and cognitive decline in older adults
      with hypertension: results from the Cardiovascular Health Study.
AB  - BACKGROUND: Hypertension (HTN) is a risk factor for dementia, and animal studies
      suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors
      (those that cross the blood-brain barrier) may protect against dementia beyond
      HTN control. METHODS: Participants in the Cardiovascular Health Study Cognition
      Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054;
      mean age, 75 years) were followed up for a median of 6 years to determine whether
      cumulative exposure to ACE inhibitors (as a class and by central activity),
      compared with other anti-HTN agents, was associated with a lower risk of incident
      dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]),
      or incident disability in instrumental activities of daily living (IADLs).
      RESULTS: Among 414 participants who were exposed to ACE inhibitors and 640 who
      were not, there were 158 cases of incident dementia. Compared with other anti-HTN
      drugs, there was no association between exposure to all ACE inhibitors and risk
      of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15),
      difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability
      in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were
      similar. However, centrally active ACE inhibitors were associated with 65% less
      decline in 3MSE scores per year of exposure (P = .01), and noncentrally active
      ACE inhibitors were associated with a greater risk of incident dementia (adjusted
      HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability
      in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared
      with other anti-HTN drugs. CONCLUSIONS: While ACE inhibitors as a class do not
      appear to be independently associated with dementia risk or cognitive decline in
      older hypertensive adults, there may be within-class differences in regard to
      these outcomes. These results should be confirmed with a randomized clinical
      trial of a centrally active ACE inhibitor in the prevention of cognitive decline
      and dementia.

PMID- 19597069
TI  - Optimal level of oral anticoagulant therapy for the prevention of arterial
      thrombosis in patients with mechanical heart valve prostheses, atrial
      fibrillation, or myocardial infarction: a prospective study of 4202 patients.
AB  - BACKGROUND: Oral anticoagulant therapy is effective for the prevention of
      arterial thromboembolism in various patient groups. The increased risk of
      hemorrhage remains the major drawback to this therapy and is associated with the
      intensity of anticoagulation. Finding the optimal intensity at which the overall
      incidence rate of both bleeding and thromboembolic events is minimized represents
      a way to improve the safety of oral anticoagulant treatment. METHODS: We
      evaluated all patients visiting the Leiden Anticoagulation Clinic with mechanical
      heart valve prostheses, atrial fibrillation, or myocardial infarction from 1994
      to 1998. Untoward events were major thromboembolism and major hemorrhage. We
      calculated intensity-specific incidence rates of untoward events to assess the
      optimal intensity per indication of treatment. We enrolled 4202 patients for a
      total of 7788 patient-years. RESULTS: A total of 3226 hospital admissions were
      reported, 306 owing to an untoward event. Incidence rates of untoward events were
      around 4% per year for all indications: 4.3 (95% confidence interval [CI], 3.1
      5.6) for patients with mechanical heart valve prostheses, 4.3 (95% CI, 3.7-5.1)
      for patients with atrial fibrillation, and 3.6 per year (95% CI, 3.0-4.4) for
      patients treated after a myocardial infarction. The optimal intensity of
      anticoagulation for patients with mechanical heart valve prostheses was an
      international normalized ratio (INR) of 2.5 to 2.9; for patients with atrial
      fibrillation, an INR of 3.0 to 3.4; and for patients after myocardial infarction,
      an INR of 3.5 to 3.9. CONCLUSION: Our study suggests target INRs of 3.0 for
      patients with mechanical heart valve prostheses and atrial fibrillation and 3.5
      after myocardial infarction as a starting point in future clinical trials.

PMID- 19597070
TI  - Thrombomodulin as a marker for bleeding complications during warfarin treatment.
AB  - BACKGROUND: The major adverse effect of warfarin treatment is hemorrhage. Several
      risk factors for bleeding complications are also risk factors for thromboembolic
      events, making the clinical decision to initiate or withhold anticoagulant
      treatment difficult. Specific markers that solely identify patients at high risk
      of bleeding would have great clinical impact. This study aimed to test if
      thrombomodulin (TM) concentrations were associated with bleeding complications,
      cardiovascular events, or mortality in long-term anticoagulant-treated patients.
      METHODS: In a longitudinal cohort study we followed up 719 patients receiving
      warfarin treatment for a mean duration of 4.2 years. All bleeding complications
      causing hospitalization were registered and classified. Soluble TM antigen (sTM)
      concentration in plasma was measured with an enzyme-linked immunosorbent assay
      method. RESULTS: During the follow-up time, 113 clinically relevant bleeding
      events and 73 major bleeding events occurred. Increased concentration of sTM was
      associated with both clinically relevant bleeding and major bleeding events after
      adjustment for age. In the multivariable models, hazard ratios for the highest
      tertiles compared with the lowest were 2.29 (95% confidence interval, 1.35-3.89)
      and 2.33 (95% confidence interval, 1.21-4.48), respectively. No association
      between sTM concentration and nonfatal ischemic cardiovascular events or all
      cause mortality was found. CONCLUSIONS: Increased levels of sTM are associated
      with bleeding complications during warfarin treatment but not with cardiovascular
      events or all-cause mortality. Soluble TM antigen concentration has potential as
      a new specific marker to identify patients at high risk of bleeding during
      warfarin treatment.

PMID- 19597071
TI  - Active commuting and cardiovascular disease risk: the CARDIA study.
AB  - BACKGROUND: There is little research on the association of lifestyle exercise,
      such as active commuting (walking or biking to work), with obesity, fitness, and
      cardiovascular disease (CVD) risk factors. METHODS: This cross-sectional study
      included 2364 participants enrolled in the Coronary Artery Risk Development in
      Young Adults (CARDIA) study who worked outside the home during year 20 of the
      study (2005-2006). Associations between walking or biking to work (self-reported
      time, distance, and mode of commuting) with body weight (measured height and
      weight); obesity (body mass index [BMI], calculated as weight in kilograms
      divided by height in meters squared, >or= 30); fitness (symptom-limited exercise
      stress testing); objective moderate-vigorous physical activity (accelerometry);
      CVD risk factors (blood pressure [oscillometric systolic and diastolic]); and
      serum measures (fasting measures of lipid, glucose, and insulin levels) were
      separately assessed by sex-stratified multivariable linear (or logistic)
      regression modeling. RESULTS: A total of 16.7% of participants used any means of
      active commuting to work. Controlling for age, race, income, education, smoking,
      examination center, and physical activity index excluding walking, men with any
      active commuting (vs none) had reduced likelihood of obesity (odds ratio [OR],
      0.50; 95% confidence interval [CI], 0.33-0.76), reduced CVD risk: ratio of
      geometric mean triglyceride levels (trig(active))/(trig(nonactive)) = 0.88 (95%
      CI, 0.80 to 0.98); ratio of geometric mean fasting insulin
      (FI(active))/(FI(nonactive)) = 0.86 (95% CI, 0.78 to 0.93); difference in mean
      diastolic blood pressure (millimeters of mercury) (DBP(active)) -
      (DBP(nonactive)) = -1.67 (95% CI, -3.20 to -0.15); and higher fitness: mean
      difference in treadmill test duration (in seconds) in men (TT(active)) -
      (TT(nonactive)) = 50.0 (95% CI, 31.45 to 68.59) and women (TT(active)) -
      (TT(nonactive)) = 28.77 (95% CI, 11.61 to 45.92). CONCLUSIONS: Active commuting
      was positively associated with fitness in men and women and inversely associated
      with BMI, obesity, triglyceride levels, blood pressure, and insulin level in men.
      Active commuting should be investigated as a modality for maintaining or
      improving health.

PMID- 19597074
TI  - Effect of sample medication restrictions on prescribing at a private clinic.

PMID- 19597073
TI  - A pooled analysis of the effect of condoms in preventing HSV-2 acquisition.
AB  - BACKGROUND: The degree of effectiveness of condom use in preventing the
      transmission of herpes simplex virus 2 (HSV-2) is uncertain. To address this
      issue, we performed a large pooled analysis. METHODS: We identified prospective
      studies with individual-level condom use data and laboratory-defined HSV-2
      acquisition. Six studies were identified through a review of publications through
      2007: 3 candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational
      sexually transmitted infection (STI) incidence study, and a behavioral STI
      intervention study. Study investigators provided us individual-level data to
      perform a pooled analysis. Effect of condom use was modeled using a continuous
      percentage of sex acts during which a condom was used and, alternatively, using
      absolute numbers of unprotected sex acts. RESULTS: A total of 5384 HSV-2-negative
      people at baseline contributed 2 040 894 follow-up days; 415 persons acquired
      laboratory-documented HSV-2 during follow-up. Consistent condom users (used 100%
      of the time) had a 30% lower risk of HSV-2 acquisition compared with those who
      never used condoms (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.40
      0.94) (P = .01). Risk for HSV-2 acquisition increased steadily and significantly
      with each unprotected sex act (HR, 1.16; 95% CI, 1.08-1.25) (P < .001). Condom
      effectiveness did not vary by gender. CONCLUSIONS: To our knowledge, this is the
      largest analysis using prospective data to assess the effect of condom use in
      preventing HSV-2 acquisition. Although the magnitude of protection was not as
      large as has been observed with other STIs, we found that condoms offer moderate
      protection against HSV-2 acquisition in men and women.

PMID- 19597075
TI  - Improving the clinician-scientist pathway: a survey of clinician-scientists.

PMID- 19597076
TI  - Even more to do and even less time: resident education and the future of primary
      care.

PMID- 19597077
TI  - How efficient is procalcitonin-guided antibiotic use in acute respiratory tract
      infections in primary care?

PMID- 19597072
TI  - Modified directly observed antiretroviral therapy compared with self-administered
      therapy in treatment-naive HIV-1-infected patients: a randomized trial.
AB  - BACKGROUND: Success of antiretroviral therapy depends on high rates of adherence,
      but few interventions are effective. Our objective was to determine if modified
      directly observed therapy (mDOT) improves initial antiretroviral success.
      METHODS: In an open-label, randomized trial comparing mDOT (Monday-Friday for 24
      weeks) and self-administered therapy with lopinavir/ritonavir soft gel capsules
      (800 mg/200 mg), emtricitabine (200 mg), and either extended-release stavudine
      (100 mg) or tenofovir (300 mg), all taken once daily, 82 participants received
      mDOT and 161, self-administered therapy. Participant eligibility included a
      plasma human immunodeficiency virus RNA level higher than 2000 copies/mL and
      being naive to antiretroviral therapy. A total of 243 participants were
      predominantly male (79%) (median age, 38 years), with 84 Latinos (35%), 74 non
      Latino blacks (30%), and 79 non-Latino whites (33%). The study was conducted at
      23 AIDS Clinical Trials Group (ACTG) sites in the United States and 1 site in
      South Africa between October 2002 and January 2006. The primary outcome was
      virologic success at week 24 and secondary outcomes were virologic success,
      clinical progression, and adherence at week 48. RESULTS: Over 24 weeks, mDOT had
      greater virologic success (0.91; 95% confidence interval [CI], 0.81 to 0.95) than
      self-administered therapy (0.84; 95% CI, 0.77 to 0.89), but the difference (0.07;
      lower bound 95% CI, -0.01) did not reach the prespecified threshold of 0.075.
      Over 48 weeks, virologic success was not significantly different between mDOT
      (0.72; 95% CI, 0.61 to 0.81) and self-administered therapy (0.78; 95% CI, 0.70 to
      0.84) (difference, -0.06; 95% CI, -0.18 to 0.07 [P = .19]). CONCLUSIONS: The
      potential benefit of mDOT was marginal and not sustained after discontinuation.
      Modified DOT should not be incorporated routinely for care of treatment-naive
      human immunodeficiency virus type 1-infected patients.

PMID- 19597078
TI  - Tuberculosis and substance abuse.

PMID- 19597079
TI  - Treatment of type 2 diabetes: one extreme to another.

PMID- 19597080
TI  - Changing the diabetes treatment paradigm.

PMID- 19597081
TI  - Determinants of the timing of symptomatic treatment in early Parkinson disease:
      The National Institutes of Health Exploratory Trials in Parkinson Disease (NET
      PD) Experience.
AB  - OBJECTIVE: To assess the predictive value of baseline measures of impairment,
      disability, and quality of life for the timing of initiation of symptomatic
      treatment in early Parkinson disease (PD). DESIGN: Inception cohort analysis.
      SETTING: Ambulatory population from multiple sites in the United States and
      Canada. PARTICIPANTS: Four hundred thirteen patients with early, untreated PD who
      participated in 2 double-blind trials that assessed the potential of experimental
      drugs to serve as disease-modifying agents in PD. Intervention Participants were
      randomized into treatment groups: creatine (n = 67), minocycline (n = 66),
      coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). Main Outcome
      Measure Time between baseline assessment and need for the initiation of
      symptomatic treatment for PD. The following baseline variables were assessed for
      their relation to the main outcome measure, while adjusting for possible
      treatment effect: sex; age; level of education; race/ethnicity; disease duration;
      occupational status; and Unified Parkinson Disease Rating Scale (UPDRS), Medical
      Outcomes Study Short Form Survey, Modified Rankin Scale, Schwab and England
      Activities of Daily Living Scale, Total Functional Capacity Scale, 39-item
      Parkinson Disease Questionnaire, and Geriatric Depression Scale scores. Variables
      reaching statistical threshold in univariate analyses (alpha = .15) were entered
      into a multivariable Cox proportional hazards regression model using time to
      symptomatic treatment as the dependent variable. RESULTS: Approximately half
      (48.5%) of the participants reached end point within 12 months. Higher baseline
      impairment and disability, as determined by UPDRS III (motor section), UPDRS II
      (activities of daily living section, participant rating), and Modified Rankin
      Scale scores and level of education were independently associated with an earlier
      need for symptomatic treatment. CONCLUSIONS: In early PD, greater impairment and
      disability and higher level of education are independently associated with an
      earlier need for symptomatic treatment.

PMID- 19597082
TI  - Capturing the scope of stroke: silent, whispering, and overt.

PMID- 19597083
TI  - Emerging therapies for relapsing multiple sclerosis.
AB  - Six agents are currently approved by regulatory agencies to treat relapsing
      multiple sclerosis. Although these agents are effective and generally safe, some
      patients have continued disease activity or adverse effects. A sizable number of
      new agents are under investigation currently. This article reviews emerging
      agents that have shown promise in phase 2 trials.

PMID- 19597084
TI  - Neurobiological changes in the hippocampus during normative aging.
AB  - The number of individuals older than 65 years is projected to exceed 71.5 million
      in the year 2030, which is twice the number alive during the year 2000. While
      this dramatic increase in the number of individuals at risk for Alzheimer and
      vascular disease will pose a significant challenge to the health care industry,
      many older individuals will not actually die of these age-related dementias.
      Instead, a significant proportion of those older than 65 years will have to cope
      with alterations in memory function that are associated with normative aging. A
      clear understanding of the neurobiological mechanisms underlying normal age
      related changes will be essential in helping elderly populations maintain
      cognitive performance with increasing age. This review covers the major age
      related alterations in the hippocampus, a critical structure for learning and
      memory.

PMID- 19597085
TI  - Association between clinical conversion to multiple sclerosis in radiologically
      isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual
      evoked potential: follow-up of 70 patients.
AB  - BACKGROUND: Subclinical demyelinating lesions may occur in the brains of
      asymptomatic individuals. OBJECTIVE: To describe the clinical and magnetic
      resonance imaging (MRI) follow-up of patients with subclinical demyelinating
      lesions that fulfill the Barkhof/Tintore criteria. DESIGN: Prospective study.
      SETTING: University-affiliated teaching hospitals. PATIENTS: Fifty-three women
      and 17 men with subclinical demyelinating lesions (mean age, 35.63 years). MAIN
      OUTCOME MEASURES: Cerebrospinal fluid, MRI, and visual evoked potential
      measurements. METHODS: All patients underwent their first brain MRI for various
      medical problems that were not suggestive of multiple sclerosis (MS). The
      patients' physicians proposed that they undergo paraclinical studies (blood,
      cerebrospinal fluid, and visual evoked potential analysis) and follow-up with
      MRI. RESULTS: Twenty-three patients (33%) had clinical conversion: 6 to optic
      neuritis, 6 to myelitis, 5 to brainstem symptoms, 4 to sensitive symptoms, 1 to
      cerebellar symptoms, and 1 to cognitive deterioration. The mean time between the
      first brain MRI and the first clinically isolated syndrome was 2.3 years (range,
      0.8-5.0 years). Twelve patients had been treated with immunomodulators after a
      clinically isolated syndrome. Examination of pejorative markers for clinical
      conversion showed that sex, number of T2 lesions, presence of oligoclonal bands,
      and IgG index were not statistically different in patients with MS determined by
      MRI compared with clinically definite MS. Visual evoked potential abnormalities,
      young age, and gadolinium enhancement on follow-up MRI were more frequent in
      clinically definite MS than in MS determined by MRI. CONCLUSIONS: In this cohort,
      we determined the rate of clinical conversion (33%) during a mean follow-up of
      5.2 years. To our knowledge, this is the first clinically isolated syndrome
      cohort with preclinical follow-up. Early treatment of these patients with MS
      determined by MRI should be discussed.

PMID- 19597088
TI  - Frequency, characteristics, and risk factors for amiodarone neurotoxicity.
AB  - OBJECTIVE: To assess the incidence, severity, and spectrum of neurologic toxic
      effects associated with administration of amiodarone hydrochloride. DESIGN:
      Retrospective medical record analysis of cardiac patients treated with amiodarone
      between January 1, 1996, and July 31, 2008. SETTING: Residents of Olmsted County,
      Minnesota, treated at the Mayo Clinic. PATIENTS: The Mayo Clinic medical records
      of all adult Olmsted County residents prescribed amiodarone between January 1,
      1996, and July 31, 2008, were reviewed and all possible neurologic adverse
      effects that might be attributable to amiodarone were tabulated. MAIN OUTCOME
      MEASURES: Risk factors and clinical characteristics of patients developing
      neurologic problems were compared with those who did not. RESULTS: Over the 151
      months of analysis, 707 patients were treated with amiodarone. Among these
      patients, the cumulative incidence of likely amiodarone neurotoxic effects was
      2.8%; 1.6% of all amiodarone-treated patients were referred to Neurology for a
      neurotoxic reaction. Neurologic problems included tremor, gait ataxia, peripheral
      neuropathy, and cognitive impairment. The primary risk factor for amiodarone
      neurotoxic effects was duration of treatment, not age, drug dose, sex, or
      indication for therapy. Where this could be assessed, the adverse effects were
      usually but not always reversible. CONCLUSIONS: Amiodarone infrequently causes
      clinically significant neurologic toxic effects. Substantially higher estimates
      of neurotoxic effects in the early amiodarone era may be related to a much higher
      daily dose.

PMID- 19597086
TI  - Genomic susceptibility Loci for brain atrophy, ventricular volume, and
      leukoaraiosis in hypertensive sibships.
AB  - OBJECTIVE: To localize susceptibility genes for alterations in brain structure
      associated with risk of stroke and dementia. We conducted genomewide linkage
      analyses for magnetic resonance imaging (MRI) measures of brain atrophy,
      ventricular, and subcortical white matter hyperintensity (leukoaraiosis) in 689
      non-Hispanic white (673 sibling pairs; median age, 61 years) and 544 non-Hispanic
      black participants (503 sibling pairs; median age, 64 years) from sibships with
      at least 2 members with essential hypertension. DESIGN, SETTING, AND PATIENTS: We
      determined brain, ventricular, and leukoaraiosis volumes from axial fluid
      attenuated inversion recovery MRI; we calculated brain atrophy as the difference
      between total intracranial and brain volumes. Microsatellite markers (n = 451)
      distributed across the 22 autosomes were genotyped, and we used variance
      components methods to estimate heritability and assess evidence of genetic
      linkage for each MRI measure. MAIN OUTCOME MEASURES: Brain atrophy ventricular
      volume, and leukoaraiosis determined from fluid-attenuated inversion recovery
      MRI. RESULTS: In both races, the heritability of each MRI measure was
      statistically greater than 0 (P < .001), ranging in magnitude from 0.42 (for
      ventricular volume in blacks) to 0.69 (for brain atrophy in blacks). Based on
      multipoint logarithm of odds scores (MLS), the strongest evidence of genetic
      linkage was observed for brain atrophy on chromosomes 1 (MLS, 3.49 at 161 cM; P <
      .001) and 17 (MLS, 3.08 at 18 cM; P < .001) in whites; for ventricular volume on
      chromosome 12 (MLS, 3.67 at 49 cM; P < .001) in blacks and chromosome 10 (MLS,
      2.47 at 110 cM; P < .001) in whites; and for leukoaraiosis on chromosome 11 (MLS,
      2.21 at 118 cM; P < .001) in whites and chromosome 22 (MLS, 2.02 at 36 cM; P =
      .001) in blacks. CONCLUSIONS: The MRI measures of structural brain injury are
      heritable in non-Hispanic black and white sibships ascertained through
      hypertensive sibling pairs. The susceptibility loci for brain atrophy,
      ventricular volume, and leukoaraiosis identified by linkage analyses differ among
      MRI measures and between races.

PMID- 19597087
TI  - Smoking and disease progression in multiple sclerosis.
AB  - BACKGROUND: Although cigarette smokers are at increased risk of developing
      multiple sclerosis (MS), the effect of smoking on the progression of MS remains
      uncertain. OBJECTIVE: To establish the relationship between cigarette smoking and
      progression of MS using clinical and magnetic resonance imaging outcomes DESIGN:
      Cross-sectional survey and longitudinal follow-up for a mean of 3.29 years,
      ending January 15, 2008. SETTING: Partners MS Center (Boston, Massachusetts), a
      referral center for patients with MS. PATIENTS: Study participants included 1465
      patients with clinically definite MS (25.1% men), with mean (range) age at
      baseline of 42.0 (16-75) years and disease duration of 9.4 (0-50.4) years. Seven
      hundred eighty patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers,
      and 257 (17.5%) were current smokers. MAIN OUTCOME MEASURES: Smoking groups were
      compared for baseline clinical and magnetic resonance imaging characteristics as
      well as progression and sustained progression on the Expanded Disability Status
      Scale at 2 and 5 years and time to disease conversion to secondary progressive
      MS. In addition, the rate of on-study change in the brain parenchymal fraction
      and T2 hyperintense lesion volume were compared. RESULTS: Current smokers had
      significantly worse disease at baseline than never-smokers in terms of Expanded
      Disability Status Scale score (adjusted P < .001), Multiple Sclerosis Severity
      Score (adjusted P < .001), and brain parenchymal fraction (adjusted P = .004). In
      addition, current smokers were significantly more likely to have primary
      progressive MS (adjusted odds ratio, 2.41; 95% confidence interval, 1.09-5.34).
      At longitudinal analyses, MS in smokers progressed from relapsing-remitting to
      secondary progressive disease faster than in never-smokers (hazard ratio for
      current smokers vs never-smokers, 2.50; 95% confidence interval, 1.42-4.41). In
      addition, in smokers, the T2-weighted lesion volume increased faster (P = .02),
      and brain parenchymal fraction decreased faster (P = .02). CONCLUSION: Our data
      suggest that cigarette smoke has an adverse influence on the progression of MS
      and accelerates conversion from a relapsing-remitting to a progressive course.

PMID- 19597089
TI  - Elevated serum pesticide levels and risk of Parkinson disease.
AB  - BACKGROUND: Exposure to pesticides has been reported to increase the risk of
      Parkinson disease (PD), but identification of the specific pesticides is lacking.
      Three studies have found elevated levels of organochlorine pesticides in
      postmortem PD brains. OBJECTIVE: To determine whether elevated levels of
      organochlorine pesticides are present in the serum of patients with PD. DESIGN:
      Case-control study. SETTING: An academic medical center. PARTICIPANTS: Fifty
      patients with PD, 43 controls, and 20 patients with Alzheimer disease. MAIN
      OUTCOME MEASURES: Levels of 16 organochlorine pesticides in serum samples.
      RESULTS: beta-Hexachlorocyclohexane (beta-HCH) was more often detectable in
      patients with PD (76%) compared with controls (40%) and patients with Alzheimer
      disease (30%). The median level of beta-HCH was higher in patients with PD
      compared with controls and patients with Alzheimer disease. There were no marked
      differences in detection between controls and patients with PD concerning any of
      the other 15 organochlorine pesticides. Finally, we observed a significant odds
      ratio for the presence of beta-HCH in serum to predict a diagnosis of PD vs
      control (odds ratio, 4.39; 95% confidence interval, 1.67-11.6) and PD vs
      Alzheimer disease (odds ratio, 5.20), which provides further evidence for the
      apparent association between serum beta-HCH and PD. CONCLUSIONS: These data
      suggest that beta-HCH is associated with a diagnosis of PD. Further research is
      warranted regarding the potential role of beta-HCH as a etiologic agent for some
      cases of PD.

PMID- 19597090
TI  - Dysfunction of the default mode network in Parkinson disease: a functional
      magnetic resonance imaging study.
AB  - OBJECTIVE: To examine the integrity of the default mode network in patients with
      Parkinson disease (PD). Previous functional neuroimaging experiments have studied
      executive deficits in patients with PD with regard to task-related brain
      activation. However, recent studies suggest that executive performance also
      relies on the integrity of the default mode network (ie, medial prefrontal
      cortex, posterior cingulate cortex, precuneus, and lateral parietal and medial
      temporal cortices), characterized by a deactivation of these cortical areas
      during the performance of executive tasks. DESIGN: We used functional magnetic
      resonance imaging to investigate cortical deactivations during a card-sorting
      task (retrieval and manipulation of short-term memory contents) compared with a
      simple sensory-motor matching task. In addition, a functional connectivity
      analysis was performed. SETTING: Tertiary outpatient clinic. PARTICIPANTS: Seven
      patients with mild to moderate PD (not taking medication) and 7 healthy controls.
      MAIN OUTCOME MEASURE: Cortical deactivations. RESULTS: Both groups showed
      comparable deactivation of the medial prefrontal cortex but different
      deactivation in the posterior cingulate cortex and the precuneus. Compared with
      controls, patients with PD not only showed less deactivation of the posterior
      cingulate cortex and the precuneus, they even demonstrated a reversed pattern of
      activation and deactivation. Connectivity analysis yielded that in contrast to
      healthy individuals, medial prefrontal cortex and the rostral ventromedial
      caudate nucleus were functionally disconnected in PD. CONCLUSIONS: We describe
      specific malfunctioning of the default mode network during an executive task in
      PD. This finding is plausibly linked to dopamine depletion and may critically
      contribute to the understanding of executive deficits in PD.

PMID- 19597091
TI  - Neurological consequences of atrioesophageal fistula after radiofrequency
      ablation in atrial fibrillation.
AB  - BACKGROUND: Radiofrequency ablation for atrial fibrillation (RAF) is an
      increasingly performed procedure. It is performed during cardiac surgery or
      percutaneously by catheter. A dangerous complication of RAF is atrioesophageal
      fistula (AEF), which predominantly manifests neurologically owing to food
      embolism. Because neurologists may not be familiar with AEF and the prognosis is
      dependent on a prompt diagnosis, awareness of AEF by the neurologist may play a
      crucial role. OBJECTIVE: To summarize for the neurologist the knowledge about
      fistula between the left atrium and esophagus occurring after RAF. DESIGN,
      SETTING, AND PATIENTS: Using a MEDLINE search, we collected reports about AEF
      after RAF in 28 patients. MAIN OUTCOME MEASURES: From the collected reports, the
      description of symptoms, diagnostic investigations, therapy, and outcome of the
      28 patients were summarized. RESULTS: In 28 cases, AEF developed 3 to 38 days
      after RAF. Confusion, grand mal seizures, meningitis, focal cortical signs, and
      postprandial transient ischemic attacks associated with fever were the leading
      manifestations in 21 of 28 patients. Blood tests showed leukocytosis, elevated
      serum C-reactive protein levels, and thrombocytopenia. Blood cultures were
      frequently positive for bacteria. Lumbar puncture revealed pleocytosis, elevated
      protein levels, increased lactate levels, and bacteria. Diagnosis was established
      by thoracic contrast computed tomography. Endoscopy, insertion of nasogastric
      tubes, and transesophageal echocardiography were detrimental, leading to an
      increase in fistula size and food or air embolism. Therapy comprised surgery (n =
      11) or temporary esophageal stenting (n = 1). The remaining patients died before
      attempted surgery or confirmation of the diagnosis. A neurological deficit
      persisted in 3 of the 9 surviving patients. CONCLUSIONS: In patients with
      meningitis, stroke, seizures, or impaired consciousness and fever, it should be
      determined whether they have had a previous RAF. In cases with a history of
      recent RAF, AEF should be strongly considered, especially if there are also
      symptoms such as dysphagia or chest pain. After RAF, the patient, his or her
      family, and his or her treating physicians should be informed about the signs of
      AEF, which may occur even weeks after RAF.

PMID- 19597092
TI  - Apathy symptom profile and behavioral associations in frontotemporal dementia vs
      dementia of Alzheimer type.
AB  - BACKGROUND: Apathy is a common and significant problem in patients with dementia,
      regardless of its cause. Observations about frontosubcortical circuit syndromes
      indicate that apathy may have affective, behavioral, or cognitive manifestations.
      OBJECTIVES: To explore whether the apathy manifested in frontotemporal dementia
      (FTD), with its predominantly anterior brain neuropathologic features, differs
      from the apathy in dementia of Alzheimer type (DAT), with its predominantly
      hippocampal- and temporoparietal-based neuropathologic features, and to determine
      whether other behavioral disturbances reported in frontosubcortical circuit
      syndromes correlate with apathy. DESIGN: Analyses included individual items
      within Neuropsychiatric Inventory subscale items. Items of the
      apathy/indifference subscale were designated by consensus as affective (lacking
      in emotions), behavioral (inactive, chores abandoned), or cognitive (no interest
      in the activities of others). Proportions of correlated nonapathy
      Neuropsychiatric Inventory items were calculated. SETTING: Several neurology
      specialty clinics contributed to our data set. PARTICIPANTS: A total of 92
      participants with FTD and 457 with DAT. MAIN OUTCOME MEASURES: The
      Neuropsychiatric Inventory was analyzed. RESULTS: Apathy was more prevalent in
      patients with FTD than in those with DAT, but when present, the specific apathy
      symptoms associated with both types of dementia were rarely restricted to 1 of
      the 3 domains of apathy. Dysphoria concurrent with apathy was unique to the DAT
      group and negatively correlated in the FTD group. Participants with affective
      apathy more frequently copresented with an orbital frontosubcortical syndrome in
      FTD (impulsivity and compulsions). Affective apathy also copresented with
      uncooperative agitation, anger, and physical agitation in both types of dementia.
      CONCLUSIONS: Apathy is common in patients with FTD and DAT, although it is more
      common in those with FTD. When present, it usually involves changes in affect,
      behavior, and cognition. It is associated with behaviors that have previously
      been shown to affect patient safety, independence, and quality of life.

PMID- 19597094
TI  - Progressive myoclonus epilepsy with demyelinating peripheral neuropathy and
      preserved intellect: a novel syndrome.
AB  - BACKGROUND: The progressive myoclonic epilepsies (PMEs) are a disparate group of
      syndromes whose common features include disabling myoclonus, progressive
      cognitive decline, and seizures, typically with a relentless deterioration over
      time. OBJECTIVE: To report a novel PME syndrome. DESIGN: Case report. SETTING:
      Epilepsy service in a tertiary care urban medical center. PATIENT: A 24-year-old
      man with progressive myoclonus, seizures, and unique features of preserved
      intellect and demyelinating peripheral neuropathy. MAIN OUTCOME MEASURE: Detailed
      clinical assessment, electrophysiologic studies, and survey of the literature.
      RESULTS: We characterize an unusual PME phenotype with unique features of
      preserved intellect and electrophysiologic evidence of a generalized
      demyelinating peripheral neuropathic condition. An extensive diagnostic
      evaluation did not reveal an underlying cause, and a literature survey did not
      identify other, similar clinical reports. CONCLUSION: We describe a novel PME
      syndrome with preserved intellect and demyelinating peripheral neuropathy.

PMID- 19597093
TI  - Priapism in infantile transverse myelitis.
AB  - BACKGROUND: Transverse myelitis is an autoimmune neurological disorder of the
      spinal cord that affects individuals of all age groups, including infants.
      OBJECTIVE: To report priapism as a unique clinical manifestation of infantile
      transverse myelitis. DESIGN: Case series. SETTING: Transverse Myelitis Center at
      Johns Hopkins, Johns Hopkins Hospital, Baltimore, Maryland. PATIENTS: Three
      infants younger than 12 months. INTERVENTIONS: Intravenous corticosteroids,
      intravenous immunoglobulin, physical therapy, and rehabilitation. MAIN OUTCOME
      MEASURE: Clinical outcomes in infants with priapism and transverse myelitis.
      RESULTS: All 3 infants demonstrated rapidly progressive quadriplegia that
      resulted in substantial disability and proved fatal for 1 infant. CONCLUSION:
      Priapism in infants with transverse myelitis may be an indication of severe
      inflammation and neural injury that necessitates immediate and aggressive
      treatment.

PMID- 19597095
TI  - Diagnostic utility of ultrasound in posterior interosseous nerve syndrome.

PMID- 19597096
TI  - Polyradiculitis as a predominant symptom of tick-borne encephalitis virus
      infection.

PMID- 19597097
TI  - Vein of galen aneurysmal malformation treated with Onyx.

PMID- 19597098
TI  - APOE epsilon 2/epsilon 4 genotype a risk factor for primary progressive aphasia
      in women.

PMID- 19597099
TI  - Mediterranean dietary pattern, mild cognitive impairment, and progression to
      dementia.

PMID- 19597100
TI  - Parkinson disease: extranigral, multisystem, and {alpha}-synuclein "plus".

PMID- 19597101
TI  - Reversible autoimmune encephalopathy spectrum.

PMID- 19597102
TI  - Four-year follow-up of posterior chamber phakic intraocular lens implantation for
      moderate to high myopia.
AB  - OBJECTIVE: To assess the long-term clinical outcomes of implantation of a lens
      consisting of a biocompatible collagen copolymer (Visian implantable Collamer
      lens [ICL]; STAAR Surgical, Nidau, Switzerland) for moderate to high myopia.
      METHODS: We evaluated 56 eyes of 34 patients with myopic refractive errors of 
      4.00 to -15.25 diopters (D) who underwent ICL implantation and routine
      postoperative examinations. Before and 1, 3, and 6 months and 1, 2, and 4 years
      after surgery, we assessed the safety, efficacy, predictability, stability, and
      adverse events of the surgery. RESULTS: Mean (SD) logMAR uncorrected and best
      spectacle-corrected visual acuities were -0.03 (0.23) and -0.21 (0.09),
      respectively, at 4 years after surgery. The mean (SD) safety and efficacy indexes
      were 1.19 (0.25) and 0.83 (0.29), respectively. At 4 years, 44 (79%) and 52 (93%)
      of the eyes were within +/-0.5 and +/-1.0 D, respectively, of the targeted
      correction. Mean (SD) manifest refraction changes of -0.24 (0.57) D occurred from
      1 month to 4 years after surgery. No vision-threatening complications occurred
      during the observation period. CONCLUSION: Implantation of ICLs is safe and
      effective and provides predictable and stable refractive results in the treatment
      of moderate to high myopia during a 4-year observation period, suggesting its
      viability as a surgical option for the treatment of such eyes.

PMID- 19597103
TI  - Modalities to decrease stromal herpes simplex keratitis reactivation rates.
AB  - OBJECTIVE: To evaluate the efficacy of adjunctive treatments to decrease herpes
      simplex keratitis (HSK) recurrences in patients with simultaneous stromal HSK and
      dry eye disease. METHODS: This was a nonrandomized, single-center, retrospective,
      comparative analysis. Forty-two patients were diagnosed with unilateral HSK and
      dry eye disease. Of the 42 patients, 22 were treated with ipsilateral punctal
      occlusion by thermal cautery and 10 were treated with topical administration of
      cyclosporine, 0.05%, ophthalmic emulsion twice a day. Another group of 10
      patients had previously undergone punctal occlusion and had cyclosporine
      ophthalmic emulsion twice a day added. All patients continued the use of oral
      acyclovir or valacyclovir hydrochloride and topical steroids. The frequency and
      duration of HSK recurrences were monitored for 1 year after initiation of
      treatment, and the rates were compared with those in the prior year. RESULTS: The
      thermal cautery and topical cyclosporine groups experienced HSK recurrences for
      mean durations of 7.1 and 5.8 mo/y before treatment, respectively, and these were
      reduced to 1.1 mo/y after treatment in both groups. Topical administration of
      cyclosporine further reduced the duration of HSK recurrences in patients with
      prior thermal cautery from an average of 1.3 mo/y before the addition of
      cyclosporine to 0.8 mo/y after the addition of cyclosporine. CONCLUSION:
      Permanent punctal occlusion by thermal cautery and the use of topical
      cyclosporine independently reduced recurrences of stromal HSK.

PMID- 19597105
TI  - Further insight into West African crystalline maculopathy.
AB  - OBJECTIVE: To describe new features and ocular coherence tomographic scans of
      individuals with West African crystalline maculopathy (WACM). DESIGN: Prospective
      observational case series. PARTICIPANTS: All 14 patients with WACM identified in
      the medical retina clinic during a 6-month period. METHODS: Full ophthalmic
      examination and high-resolution ocular coherence tomographic imaging and
      fluorescein angiography where indicated. MAIN OUTCOME MEASURES: Ethnicity and
      dietary history of individuals, location of crystals, and associated retinal
      comorbidity. RESULTS: Patients originated from several West African countries.
      Two patients had unilateral WACM. The crystals were yellow-green in color,
      birefringent, and located in the layer of Henle of the fovea. Coexistent retinal
      pathology was present in all patients. CONCLUSIONS: Several new features of the
      condition are described. Breakdown of the blood retinal barrier may play a role
      in the formation of the crystals.

PMID- 19597104
TI  - Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve
      fiber layer and optic nerve appearance.
AB  - OBJECTIVE: To determine if panretinal photocoagulation (PRP) alters retinal nerve
      fiber layer (RNFL) thickness and optic nerve appearance. METHODS: Patients with
      diabetes who did and did not undergo PRP and nondiabetic control subjects were
      enrolled in a prospective study. Participants underwent optical coherence
      tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve
      photographs were graded in a masked fashion. RESULTS: Ninety-four eyes of 48
      healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and
      37 eyes of 24 subjects with diabetes who underwent PRP were included in this
      study. Eyes that had been treated with PRP had thinner peripapillary RNFL
      compared with the other groups; this was statistically significantly different in
      the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not
      increase with severity of disease classification, but the proportion of optic
      nerves graded as suspicious for glaucoma or as having nonglaucomatous optic
      neuropathy did (P = .008). These grading categories were associated with thinner
      RNFL measurements. CONCLUSIONS: Diabetic eyes that have been treated with PRP
      have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP
      are more likely to be graded as abnormal, but their appearance is not necessarily
      glaucomatous and may be related to thinning of the RNFL.

PMID- 19597106
TI  - Dr Thompson's Eye Water.

PMID- 19597107
TI  - Increased prevalence of autoimmunity in patients with white spot syndromes and
      their family members.
AB  - OBJECTIVE: To determine whether there is an increased prevalence of systemic
      autoimmune diseases in both patients with white spot syndromes (WSS) and their
      family members. METHODS: Patients with WSS at participating institutions were
      asked to complete a questionnaire reporting their own medical histories as well
      as any autoimmune diseases among their first- and second-degree relatives.
      RESULTS: As of January 1, 2008, 114 questionnaires had been collected, providing
      medical histories of 114 patients with WSS and 1098 family members. The number of
      patients with WSS with self-reported systemic autoimmune diseases was 26 (23%).
      Of 1098 relatives, 106 (10%) had at least 1 autoimmune disease. Systemic
      autoimmunity was more prevalent in female relatives (13%) as compared with male
      relatives (6%). In addition, the prevalence of autoimmunity was significantly
      higher among first-degree relatives (13%) than second-degree relatives (8%).
      Patients who themselves had systemic autoimmune diseases showed a greater
      prevalence of systemic autoimmunity among their families as compared with the
      families of patients without systemic autoimmune diseases. CONCLUSIONS: Our data
      indicate that there is an increased prevalence of systemic autoimmunity in both
      patients with WSS and their first- and second-degree relatives. This suggests
      that WSS occur in families with inherited immune dysregulation that predisposes
      to autoimmunity.

PMID- 19597109
TI  - Amelioration of murine dry eye disease by topical antagonist to chemokine
      receptor 2.
AB  - OBJECTIVE: To determine the effect of a topical antagonist to the chemokine
      receptor 2 (CCR2) in a murine model of dry eye disease. METHODS: The effects of a
      topical CCR2 antagonist and a vehicle control treatment were studied in murine
      dry eyes. A controlled environment chamber induced dry eye by exposing mice to
      high-flow desiccated air. Corneal fluorescein staining and enumeration of corneal
      CD11b(+) and conjunctival CD3(+) T cells were performed in the different groups.
      Real-time polymerase chain reaction was performed to quantify expression of
      different inflammatory cytokine transcripts in the cornea and conjunctiva.
      RESULTS: Eyes receiving the formulation containing CCR2 antagonist showed a
      significant decrease in corneal fluorescein staining and decreased infiltration
      of corneal CD11b(+) cells and conjunctival T cells compared with the vehicle
      treated and untreated dry eye groups. The CCR2 antagonist also significantly
      decreased messenger RNA expression levels of interleukins 1alpha and 1beta in the
      cornea, and tumor necrosis factor alpha and interleukin 1beta in the conjunctiva.
      CONCLUSION: Topical application of CCR2 antagonist is associated with significant
      improvement in dry eye disease and is reflected by a decrease in inflammation at
      the clinical, molecular, and cellular levels. Clinical Relevance Topical
      application of CCR2 antagonist may hold promise as a therapeutic modality in dry
      eye disease.

PMID- 19597108
TI  - Measurement of local retinal ganglion cell layer thickness in patients with
      glaucoma using frequency-domain optical coherence tomography.
AB  - OBJECTIVE: To explore the feasibility of obtaining a local measurement of the
      thickness of the retinal ganglion cell layer in patients with glaucoma using
      frequency-domain optical coherence tomography (fdOCT) and a computer-aided manual
      segmentation procedure. METHODS: The fdOCT scans were obtained from the
      horizontal midline for 1 eye of 26 patients with glaucoma and 20 control
      subjects. The thickness of various layers was measured with a manual segmentation
      procedure aided by a computer program. The patients were divided into low- and
      high-sensitivity groups based on their foveal sensitivity on standard automated
      perimetry. RESULTS: The RGC plus inner plexiform and the retinal nerve fiber
      layers of the low-sensitivity group were significantly thinner than those of the
      high-sensitivity group. While these layers were thinner in the patients than the
      controls, the thicknesses of inner nuclear layer and receptor layer were similar
      in all 3 groups. Further, the thinning of the retinal ganglion cell plus inner
      plexiform layer in 1 glaucoma-affected eye showed qualitative correspondence to
      the loss in 10-2 visual field sensitivity. CONCLUSIONS: Local measures of RGC
      layer thickness can be obtained from fdOCT scans using a manual segmentation
      procedure, and these measures show qualitative agreement with visual field
      sensitivity.

PMID- 19597110
TI  - Peripheral artery disease and glaucoma: the singapore malay eye study.
AB  - OBJECTIVE: To examine the relationship between peripheral artery disease (PAD)
      and glaucoma. METHODS: As part of a population-based study of 3280 persons of
      Malay descent (78.7% response) aged 40 to 80 years examined between August 1,
      2004, and June 30, 2006, the ankle-brachial index (ABI) was assessed in all
      persons with known diabetes mellitus and every fifth systematically sampled
      participant without diabetes. Peripheral artery disease was deemed present if the
      ABI was 0.9 or less. Glaucoma was diagnosed using International Society of
      Geographical and Epidemiological Ophthalmology criteria. RESULTS: Of the 922
      participants who had ABI measured, 79 (8.6%) had PAD and 42 (4.6%) had glaucoma.
      Persons with PAD were more likely to have glaucoma (11.4% vs 3.9%; age- and sex
      adjusted odds ratio [OR], 2.80; 95% confidence interval [CI], 1.26-6.24), higher
      intraocular pressure (age- and sex-adjusted mean, 16.4 vs 15.5; P = .05), and a
      larger vertical cup-disc ratio (age- and sex-adjusted mean, 0.45 vs 0.40; P =
      .02). The association of PAD with glaucoma persisted while controlling for
      hypertension, diabetes, body mass index, serum triglyceride levels, and beta
      blocker use (multivariable-adjusted OR, 2.55; 95% CI, 1.09-5.98) and was stronger
      in people with diabetes (multivariable-adjusted OR, 2.91; 95% CI, 1.14-7.44).
      CONCLUSIONS: Peripheral artery disease was related to glaucoma, supporting an
      association between large-vessel atherosclerotic disease and glaucoma. However,
      because the study sample included a high proportion of persons with diabetes,
      further research is needed to determine the relevance of these results to the
      general population.

PMID- 19597111
TI  - Population prevalence of tilted and torted optic discs among an adult Chinese
      population in Singapore: the Tanjong Pagar Study.
AB  - OBJECTIVE: To determine the prevalence of tilted and torted optic discs and
      associated risk factors among Chinese adults in Singapore. METHODS: As part of a
      population-based survey, optic disc stereophotographs of both eyes were obtained,
      and left eyes were analyzed using imaging software. A tilted optic disc was
      defined as an index of tilt (ratio of minimum to maximum optic disc diameter)
      less than 0.75. The angle of tilt was defined as the angle between the maximum
      and vertical optic disc diameter, and optic discs were graded as torted if the
      angle of tilt exceeded 15 degrees . RESULTS: Twenty-six of 739 subjects (3.5%)
      had tilted optic discs, and 478 (64.7%) had torted optic discs. Myopia was
      present in 23 of 26 eyes (88.5% [95% confidence interval, 69.9%-97.6%]) with
      tilted optic discs and in 211 of 661 eyes (31.9% [28.4%-35.6%]) without tilted
      optic discs (P < .001). On multivariate analysis, myopia (spherical equivalent)
      was a significant risk factor for tilted optic discs (P < .001). Index of tilt
      was not associated with corneal astigmatism or with cylindrical refractive error.
      Seventeen eyes (65.4%) with tilted optic discs had an optic disc morphologic
      abnormality, but none were glaucomatous. CONCLUSIONS: The prevalence of tilted
      optic discs among this Chinese population was 3.5%. Tilted optic discs were
      associated with myopia but not with glaucoma.

PMID- 19597112
TI  - Trends in annual medicare expenditures for glaucoma surgical procedures from 1997
      to 2006.
AB  - OBJECTIVE: To identify payments and changes in payments for glaucoma surgical
      procedures among Medicare beneficiaries in the United States and to evaluate
      trends in costs based on the types of procedures being performed. DESIGN:
      Retrospective analysis using 1997 through 2006 Part B Medicare Beneficiary
      Encrypted Files. The annual number of claims and payments for glaucoma surgical
      procedures were calculated, as were the rates per 100 000 beneficiaries. RESULTS:
      Overall, there were decreases in both the number of glaucoma surgical procedures
      and the amount of annual payments from 1997 to 2001 but an increase in the number
      of procedures in the following years. Trends in claims and payments vary
      according to procedure. Average payments for trabeculectomies decreased over
      time, while annual payments for cyclophotocoagulation and shunt-related
      procedures have increased. After an initial decline, there was a substantial
      increase in the number of trabeculoplasties in conjunction with advancements in
      technology and a change in the global period for reimbursement. Patterns of
      surgery rates were similar to volume of surgical procedures. CONCLUSIONS:
      Findings suggest that while the overall number of glaucoma surgical procedures is
      increasing, payments have been decreasing. Clinical and technological
      advancements and reimbursement decisions may influence surgeons' preferences and,
      therefore, costs to Medicare.

PMID- 19597113
TI  - Progression of retinal pigment epithelial alterations during long-term follow-up
      in female carriers of choroideremia and report of a novel CHM mutation.
AB  - OBJECTIVES: To report clinical and functional findings in 2 female carriers of
      choroideremia who were followed up for 11 and 17 years and who showed progression
      of fundus alterations; and to report a novel CHM mutation. METHODS: We performed
      follow-ups in 2 female carriers of choroideremia, including repeated clinical and
      electrophysiologic examinations and fundus autofluorescence. Molecular analysis
      of the CHM gene was done by direct sequencing of the coding exons. RESULTS:
      Follow-up of female carrier 327 took place during 17 years. A second female
      carrier (subject 869) with a novel gene mutation in CHM was followed up for 11
      years. The 2 carriers showed marked pigmentary alterations in the periphery of
      the retina. At the initial visit, carrier 869 had multiple small, yellowish
      flecks in the macula. Both carriers developed subnormal 30-Hz flicker responses
      on full-field electroretinography during follow-up, whereas electrooculography
      responses were normal. In both carriers, progression of fundus alterations was
      noted. Fundus autofluorescence images showed multiple small flecks with reduced
      autofluorescence. CONCLUSIONS: Over time, fundus alterations in female carriers
      of choroideremia are visible, and mild cone dysfunction might develop. Multiple
      yellowish flecks can exist in the macula. The typical mottled irregularity in
      fundus autofluorescence is a valuable diagnostic criterion that facilitates
      specific genetic testing. Clinical Relevance Fundus alterations in female
      carriers of choroideremia can progress over time and a mild generalized cone
      dysfunction can develop. Characteristic irregularities are seen in fundus
      autofluorescence imaging, which is helpful in identifying female carriers of
      choroideremia.

PMID- 19597114
TI  - Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1
      gene causing best macular dystrophy.
AB  - OBJECTIVE: To study the phenotypic characteristics of patients with a novel
      p.E292K mutation in BEST1. METHODS: Affected individuals underwent ophthalmic
      examination and testing that included photography, autofluorescence, optical
      coherence tomography, and electrophysiological testing. Their DNA was analyzed
      for BEST1 mutations. RESULTS: Five patients aged 5 to 59 years who expressed the
      p.E292K mutation in BEST1 were identified in 3 families. Electro-oculographic
      light-rise was subnormal in all probands and carriers. Carriers had normal
      findings from fundus examination, multifocal electroretinography, and visual
      acuity, and were emmetropic or myopic. Only probands had hyperopia and fundus
      findings typical of Best macular dystrophy. Optical coherence tomography of
      vitelliform lesions demonstrated retinal pigment epithelium elevation without
      subretinal fluid; atrophic lesions exhibited disruption of the hyperreflective
      outer retina-retinal pigment epithelium complex. Intense hyperautofluorescence
      correlated with the vitelliform lesion. CONCLUSIONS: Patients with the Glu292Lys
      variation in BEST1 exhibit intrafamilial and interfamilial phenotypic
      variability. A disproportionate fraction (26%) of Best disease-causing mutations
      occurs in exon 8, suggesting that the portion of protein encoded by this exon
      (amino acids 290-316) may be especially important to bestrophin's function.
      Relatively good visual acuity with vitelliform lesions can be explained by
      preservation of the outer retina, demonstrated by optical coherence tomography.
      Clinical Relevance A novel mutation in this region of BEST1 carries implications
      for disease pathogenesis.

PMID- 19597115
TI  - The Charles L. Schepens Lecture: sustaining a vision.

PMID- 19597116
TI  - The evolution of retinal surgery: a personal story.

PMID- 19597117
TI  - Medication costs matter.

PMID- 19597118
TI  - From the operating room to the board room: an oculoplastic surgeon's perspective
      on health care in America: the 2008 Wendell Hughes Lecture.

PMID- 19597119
TI  - Introduction of epithelial cells in the flap-graft interface during descemet
      stripping automated endothelial keratoplasty.

PMID- 19597120
TI  - Congenital melanocytoma manifesting as proptosis with multiple cutaneous
      melanocytic nevi and oculodermal melanosis.

PMID- 19597121
TI  - Evaluating patient discomfort, anxiety, and fear before and after ranibizumab
      intravitreous injection for wet age-related macular degeneration.

PMID- 19597122
TI  - Transconjunctival orbital invasion by methicillin-resistant Staphylococcus
      aureus.

PMID- 19597123
TI  - Potential causes of altered autofluorescence in diabetic persons.

PMID- 19597125
TI  - The Cogan Ophthalmic History Society celebrates its 22nd year.

PMID- 19597126
TI  - Impaired interleukin-8 chemokine secretion by staphylococcus aureus-activated
      epithelium and T-cell chemotaxis in cystic fibrosis.
AB  - Staphylococcus aureus is frequently isolated from lungs of patients with cystic
      fibrosis (CF). Upon lung infection with S. aureus, airway epithelial cells (AEC)
      produce high levels of chemokines that enhance T-cell chemotaxis. Although the
      number of lymphocytes is increased in the airways and bronchoalveolar lavage
      fluid of patients with CF, the mechanisms responsible for their accumulation and
      the role of S. aureus in this process are largely unknown. This study
      investigated early S. aureus impact on chemokine secretion by CF epithelial cells
      and chemotaxis of CF T cells. CF and non-CF AEC were grown in a cell culture
      model and apically stimulated with S. aureus. Supernatants were quantified for
      chemokine secretions and assayed for T-cell chemotaxis. CF AEC secreted
      constitutively larger amounts of IL-8, GROalpha, MIG, MIP-3beta, and MCP-1 than
      non-CF epithelial cells. S. aureus interaction with epithelial cells increased
      chemokine production by non-CF cells but had no effect on CF cells. Chemotaxis of
      T cells derived from patients with CF was greater than that of T cells from
      subjects without CF. Moreover, there were more CF T cells expressing CXCR1 as
      compared with non-CF T cells. Under our experimental conditions, inhibition of IL
      8 or its receptor CXCR1 resulted in a considerable decrease in T-cell chemotaxis
      (up to 80%). These data suggest that IL-8 and its receptor CXCR1 are key players
      in the chemotaxis of CF T cells and could be used as targets to develop therapies
      for CF.

PMID- 19597127
TI  - Transcription factor GATA-6 is expressed in quiescent myofibroblasts in
      idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial
      pneumonia [UIP]) is a progressive disease with poor prognosis. Characteristic
      features of IPF/UIP include fibroblastic foci, which are patchy lesions of focal,
      disarranged myofibroblasts. GATA-6 is a transcription factor linked with cell
      differentiation. Its role in the development of IPF has not previously been
      investigated. We hypothesized that GATA-6 participates in the differentiation of
      fibroblasts into myofibroblasts in IPF/UIP lungs. The expression patterns of GATA
      6, the mesenchymal marker alpha-smooth muscle actin (alpha-SMA), and markers for
      proliferation (Ki67) and apoptosis (caspase-3) were analyzed in human IPF/UIP
      tissue samples. The effects of GATA-6 overexpression and silencing were studied
      in cell cultures. The results show that the alpha-SMA-positive fibroblastic foci
      in IPF/UIP lungs are positive for GATA-6, but negative for Ki67 and caspase-3.
      Cultured human IPF/UIP fibroblasts expressed GATA-6 mRNA, whereas cells from the
      normal adult lung did not. In cultured A549 lung epithelial cells, the induction
      of GATA-6 by transforming growth factor-beta1 resulted in simultaneous expression
      of alpha-SMA and decrease of E-cadherin. The inhibition of GATA-6 expression in
      fibroblasts showed that GATA-6 mediates the alpha-SMA-inducing signal of
      transforming growth factor-beta1. In conclusion, the hallmark of IPF/UIP
      histopathology, the fibroblast focus, consists of differentiated, quiescent cells
      that prominently express GATA-6.

PMID- 19597129
TI  - Pearls & oy-sters: distal subclavian artery: a source of cerebral embolism.

PMID- 19597130
TI  - Right brain: my first tPA.

PMID- 19597128
TI  - Oxidative stress enhances toll-like receptor 3 response to double-stranded RNA in
      airway epithelial cells.
AB  - Virus infections are a major cause of chronic obstructive pulmonary disease
      (COPD) exacerbations. Recently, Toll-like receptor 3 (TLR3) has been demonstrated
      to react to double-stranded RNA (dsRNA) and to be involved in the immune
      responses after viral infections. In the present study, we examined whether
      oxidative stress, which is involved in the pathogenesis of COPD, enhances the
      responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide
      (H(2)O(2)) on the release of IL-8 from BEAS-2B cells and primary human bronchial
      epithelial cells after stimulation with polyinosine-polycytidylic acid
      [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the
      signal transduction were examined. One hundred to 150 muM H(2)O(2) significantly
      potentiated the release of IL-8 from the epithelial cells after stimulation with
      10 microg/ml poly(I:C). The H(2)O(2)-augmented IL-8 release was inhibited by
      treatment with N-acetylcysteine. One hundred micromoles of H(2)O(2) enhanced the
      translocation of nuclear factor (NF)-kappaB p65, but not that of interferon
      regulatory factor-3 (IRF-3), into the nucleus and the NF-kappaB DNA binding
      activity after poly(I:C) stimulation, which effect was inhibited not by the
      silencing of IRF-3 but by MG132, a proteasome inhibitor, or dexamethasone. One
      hundred micromoles of H(2)O(2) potentiated the TLR3 expression on the airway
      epithelial cells treated with poly(I:C). These data suggest that oxidative stress
      augments the response of TLR3 in airway epithelial cells via NF-kappaB and that
      this effect might be partly mediated by the enhancement of TLR3 expression.
      Modulation of this pathway may be a therapeutic target for viral-induced
      exacerbations of COPD.

PMID- 19597133
TI  - Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in
      Parkinson disease.
AB  - BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced
      dyskinesia (LID) are still partially obscure. LID can be considered the
      consequence of an abnormal pattern or code of activity that originates and is
      conveyed from the basal ganglia to the thalamus and the cortical motor areas.
      However, not only striatothalamocortical motor circuits but also other
      interconnected pathways could be implicated in its pathogenesis. METHODS: In a
      series of experiments, we applied repetitive transcranial magnetic stimulation
      (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson
      disease, to investigate whether modulation of cerebellothalamocortical circuits
      by means of rTMS may result in a modification of a dyskinetic state induced by
      levodopa ingestion. RESULTS: We found that a single session of cerebellar
      continuous theta burst stimulation (cTBS) was capable of transiently reducing
      LID. In the same patients, we observed that cerebellar cTBS changed the profile
      of activation of intracortical circuits in the contralateral primary motor
      cortex. Cerebellar cTBS reduced short intracortical inhibition and increased long
      intracortical inhibition, inducing a cortical reorganization that is associated
      with a reduction of LID. Furthermore, in another experiment, we observed that a 2
      week course of bilateral cerebellar cTBS induced persistent clinical beneficial
      effects, reducing peak-dose LID for up to 4 weeks after the end of the daily
      stimulation period. CONCLUSIONS: Our study demonstrates that cerebellar
      continuous theta burst stimulation has an antidyskinetic effect in Parkinson
      disease patients with levodopa-induced dyskinesia, possibly due to modulation of
      cerebellothalamocortical pathways.

PMID- 19597132
TI  - Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy
      body dementia.
AB  - BACKGROUND: Experimental studies indicate that dopaminergic neurons in the
      ventral periaqueductal gray matter (PAG) are involved in maintenance of
      wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of
      multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement
      of these neurons has not yet been explored. METHODS: We sought to determine
      whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB.
      We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female,
      age 61 +/- 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1
      female, age 79 +/- 4) with diagnosis of DLB and limbic or neocortical Lewy body
      disease, and 12 controls (7 male, 5 female, ages 67 +/- 4). Fifty-micron sections
      were immunostained for tyrosine hydroxylase (TH) or alpha-synuclein and costained
      with thionin. Cell counts were performed every 400 mum throughout the ventral PAG
      using stereologic techniques. RESULTS: Compared to the total estimated cell
      numbers in controls (21,488 +/- 8,324 cells), there was marked loss of TH neurons
      in the ventral PAG in both MSA (11,727 +/- 5,984; p < 0.01) and DLB (5,163 +/-
      1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were
      characteristic alpha-synuclein inclusions in the ventral PAG in both MSA and DLB.
      CONCLUSIONS: There is loss of putative wake-active ventral periaqueductal gray
      matter dopaminergic neurons in both multiple system atrophy and dementia with
      Lewy bodies, which may contribute to excessive daytime sleepiness in these
      conditions.

PMID- 19597136
TI  - Long-term superiority of subthalamic nucleus stimulation over pallidotomy in
      Parkinson disease.

PMID- 19597135
TI  - Seropositive myasthenia gravis: a nationwide epidemiologic study.

PMID- 19597137
TI  - Reflections: neurology and the humanities. The case of the misguided Squire.

PMID- 19597134
TI  - Cognitive impairment risk: white matter hyperintensity progression matters.
AB  - OBJECTIVE: To determine whether white matter hyperintensity (WMH) progression
      rate is a better predictor of cognitive impairment risk than baseline WMH volume
      in healthy elderly individuals. METHOD: Ninety-eight cognitively intact elderly
      subjects were followed in the Oregon Brain Aging Study. Forty-nine had at least 3
      brain MRIs and annual cognitive and neurologic assessments until diagnosed with
      persistent cognitive impairment (PCI). Brain, ventricular CSF (vCSF),
      intracranial volume (ICV), hippocampus, total WMH, periventricular (PV) WMH, and
      subcortical WMH volumes were measured. Cox proportional hazards survival analyses
      were used to assess cognitive impairment risk. RESULTS: After adjusting for age,
      apolipoprotein E4 status, incident hypertension, ICV, entry Mini-Mental State
      Examination, baseline hippocampus, and both baseline vCSF volume and rate of vCSF
      volume change, increased progression of total WMH volume (hazard ratio [HR] 1.84,
      95% confidence interval [CI] 1.3-2.7, p = 0.0007) and PV WMH volume (HR 1.94, 95%
      CI 1.3-3.1, p = 0.001) conferred higher risk of PCI, whereas baseline WMH volumes
      did not. Every 1 mL/y increase in PV WMH volume was associated with a 94%
      increased risk of PCI. CONCLUSION: Progression of total and periventricular (PV)
      white matter hyperintensity (WMH) volumes are better predictors of persistent
      cognitive impairment (PCI) than baseline WMH burden. Greater PV WMH burden
      progression is associated with the development of PCI, a potential precursor to
      Alzheimer or vascular dementia. Identification of factors that decrease WMH
      accumulation over time is needed to maintain cognitive health in our growing
      elderly population.

PMID- 19597138
TI  - Idiopathic sphenoidal defects detected by 3D computed tomography.

PMID- 19597139
TI  - Pronouncing brain death: contemporary practice and safety of the apnea test.

PMID- 19597140
TI  - Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial
      neurosurgery.

PMID- 19597141
TI  - Gastrointestinal bleeding after acute ischemic stroke.

PMID- 19597142
TI  - The genetic architecture of Down syndrome phenotypes revealed by high-resolution
      analysis of human segmental trisomies.
AB  - Down syndrome (DS), or trisomy 21, is a common disorder associated with several
      complex clinical phenotypes. Although several hypotheses have been put forward,
      it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are
      sufficient to cause DS and its associated features. Here we present a high
      resolution genetic map of DS phenotypes based on an analysis of 30 subjects
      carrying rare segmental trisomies of various regions of HSA21. By using state-of
      the-art genomics technologies we mapped segmental trisomies at exon-level
      resolution and identified discrete regions of 1.8-16.3 Mb likely to be involved
      in the development of 8 DS phenotypes, 4 of which are congenital malformations,
      including acute megakaryocytic leukemia, transient myeloproliferative disorder,
      Hirschsprung disease, duodenal stenosis, imperforate anus, severe mental
      retardation, DS-Alzheimer Disease, and DS-specific congenital heart disease
      (DSCHD). Our DS-phenotypic maps located DSCHD to a <2-Mb interval. Furthermore,
      the map enabled us to present evidence against the necessary involvement of other
      loci as well as specific hypotheses that have been put forward in relation to the
      etiology of DS-i.e., the presence of a single DS consensus region and the
      sufficiency of DSCR1 and DYRK1A, or APP, in causing several severe DS phenotypes.
      Our study demonstrates the value of combining advanced genomics with cohorts of
      rare patients for studying DS, a prototype for the role of copy-number variation
      in complex disease.

PMID- 19597143
TI  - Modeling oxygen transport in surgical tissue transfer.
AB  - Reconstructive microsurgery is a clinical technique used to transfer large
      amounts of a patient's tissue from one location used to another in order to
      restore physical deformities caused by trauma, tumors, or congenital
      abnormalities. The trend in this field is to transfer tissue using increasingly
      smaller blood vessels, which decreases problems associated with tissue harvest
      but increases the possibility that blood supply to the transferred tissue may not
      be adequate for healing. It would thus be helpful to surgeons to understand the
      relationship between the tissue volume and blood vessel diameter to ensure
      success in these operations. As a first step towards addressing this question, we
      present a simple mathematical model that might be used to predict successful
      tissue transfer based on blood vessel diameter, tissue volume, and oxygen
      delivery.

PMID- 19597144
TI  - A plant-specific calreticulin is a key retention factor for a defective
      brassinosteroid receptor in the endoplasmic reticulum.
AB  - Mammalian calreticulin (CRT) is a multifunctional Ca(2+)-binding protein involved
      in more than 40 cellular processes in various subcellular compartments, such as
      Ca(2+) storage and protein folding in the endoplasmic reticulum (ER). CRT
      homologues were discovered in plants almost 15 years ago, and recent studies
      revealed that many plant species contain 2 or more CRTs that are members of 2
      distinct families, the CRT1/2 family and the plant-specific CRT3 family. However,
      little is known about their physiological functions. Here we report ebs2 (EMS
      mutagenized bri1 suppressor 2) as an allele-specific suppressor of bri1-9, a
      dwarf Arabidopsis mutant caused by retention of a defective brassinosteroid
      receptor in the ER. EBS2 encodes the Arabidopsis CRT3 that interacts with ER
      localized bri1-9 in a glycan-dependent manner. Loss-of-function ebs2 mutations
      compromise ER retention of bri1-9 and suppress its dwarfism, whereas EBS2 over
      expression enhances its dwarf phenotype. In contrast, mutations of 2 other CRTs
      or their membrane-localized homologues calnexins had little effect on bri1-9. A
      domain-swapping experiment revealed that the positively charged C-terminal tail
      of CRT3 is crucial for its "bri1-9-retainer" function. Our study revealed not
      only a functional role for a plant-specific CRT, but also functional diversity
      among the 3 Arabidopsis CRT paralogues.

PMID- 19597145
TI  - Wild birds of declining European species are dying from a thiamine deficiency
      syndrome.
AB  - Wild birds of several species are dying in large numbers from an idiopathic
      paralytic disease in the Baltic Sea area. Here, we demonstrate strong
      relationships between this disease, breeding failure, and thiamine (vitamin B(1))
      deficiency in eggs, pulli, and full-grown individuals. Thiamine is essential for
      vertebrates, and its diphosphorylated form functions as a cofactor for several
      life sustaining enzymes, whereas the triphosphorylated form is necessary for the
      functioning of neuronal membranes. Paralyzed individuals were remedied by
      thiamine treatment. Moreover, thiamine deficiency and detrimental effects on
      thiamine-dependent enzymes were demonstrated in the yolk, liver, and brain. We
      propose that the mortality and breeding failure are part of a thiamine deficiency
      syndrome, which may have contributed significantly to declines in many bird
      populations during the last decades.

PMID- 19597146
TI  - A unified and universal explanation for Levy laws and 1/f noises.
AB  - Levy laws and 1/f noises are shown to emerge uniquely and universally from a
      general model of systems which superimpose the transmissions of many independent
      stochastic signals. The signals are considered to follow, statistically, a common
      -yet arbitrary--generic signal pattern which may be either stationary or
      dissipative. Each signal is considered to have its own random transmission
      amplitude and frequency. We characterize the amplitude-frequency randomizations
      which render the system output's stationary law and power-spectrum universal-
      i.e., independent of the underlying generic signal pattern. The classes of
      universal stationary laws and power spectra are shown to coincide, respectively,
      with the classes of Levy laws and 1/f noises--thus providing a unified and
      universal explanation for the ubiquity of these classes of "anomalous statistics"
      in various fields of science and engineering.

PMID- 19597148
TI  - Warfare rather than agriculture as a critical influence on fires in the late
      Holocene, inferred from northern Vietnam.
AB  - Fire has played an essential role in the development of human civilization. Most
      previous research suggests that frequent-fire regimes in the late Holocene were
      associated with intensification of human activities, especially agriculture
      development. Here, we analyze fire regimes recorded in the Song Hong delta area
      of Vietnam over the past 5,000 years. In the prehistoric period, 2 long-term, low
      charcoal abundance periods have been linked to periods of low humidity and cool
      climate, and 5 short-term fire regimes of 100-150 years in duration occurred at
      regular intervals of approximately 700 years. However, over the last 1,500 years,
      the number, frequency, and intensity of fire regimes clearly increased. Six
      intensified-fire regime periods in northern Vietnam during this time coincided
      with changes of Vietnamese dynasties and associated warfare and unrest. In
      contrast, agricultural development supported by rulers of stable societies at
      this time does not show a positive correlation with intensified-fire regime
      periods. Thus, warfare rather than agriculture appears to have been a critical
      factor contributing to fire regimes in northern Vietnam during the late Holocene.

PMID- 19597149
TI  - MIWI-independent small RNAs (MSY-RNAs) bind to the RNA-binding protein, MSY2, in
      male germ cells.
AB  - The germ cell-specific DNA/RNA-binding protein MSY2 binds small RNAs (MSY-RNAs)
      that are approximately 25-31 nt in length, often initiate with a 5' adenine, and
      are expressed in both germ cells and somatic cells. MSY-RNA levels do not
      decrease in Miwi or Msy2 null mice. Most MSY-RNAs map within annotated genes, but
      some are PIWI-interacting RNA (piRNA)-like and map to piRNA clusters. MSY-RNAs
      are in both nuclei and cytoplasm. In nuclei, MSY-RNAs are enriched in chromatin,
      and in the cytoplasm they are detected in both ribonucleoproteins and polysomes.

PMID- 19597150
TI  - Influence of paced maternal breathing on fetal-maternal heart rate coordination.
AB  - Pregnant mothers often report a special awareness of and bonding with their
      unborn child. Little is known about this relationship although it may offer
      potential for the assessment of the fetal condition. Recently we found evidence
      of short epochs of fetal-maternal heart rate synchronization under uncontrolled
      conditions with spontaneous maternal breathing. Here, we examine whether the
      occurrence of such epochs can be influenced by maternal respiratory arrhythmia
      induced by paced breathing at several different rates (10, 12, 15, and 20 cycles
      per minute). To test for such weak and nonstationary synchronizations among the
      fetal-maternal subsystems, we apply a multivariate synchronization analysis
      technique and test statistics based on twin surrogates. We find a clear increase
      in synchronization epochs mostly at high maternal respiratory rates in the
      original but not in the surrogate data. On the other hand, fewer epochs are found
      at low respiratory rates both in original and surrogate data. The results suggest
      that the fetal cardiac system seems to possess the capability to adjust its rate
      of activation in response to external--i.e., maternal--stimulation. Hence, the
      pregnant mothers' special awareness to the unborn child may also be reflected by
      fetal-maternal interaction of cardiac activity. Our approach opens up the chance
      to examine this interaction between independent but closely linked physiological
      systems.

PMID- 19597151
TI  - Maximum-entropy network analysis reveals a role for tumor necrosis factor in
      peripheral nerve development and function.
AB  - Gene regulatory interactions that shape developmental processes can often can be
      inferred from microarray analysis of gene expression, but most computational
      methods used require extensive datasets that can be difficult to generate. Here,
      we show that maximum-entropy network analysis allows extraction of genetic
      interactions from limited microarray datasets. Maximum-entropy networks indicated
      that the inflammatory cytokine TNF-alpha plays a pivotal role in Schwann cell
      axon interactions, and these data suggested that TNF mediates its effects by
      orchestrating cytoplasmic movement and axon guidance. In vivo and in vitro
      experiments confirmed these predictions, showing that Schwann cells in TNF(-/-)
      peripheral sensory bundles fail to envelop axons efficiently, and that
      recombinant TNF can partially correct these defects. These data demonstrate the
      power of maximum-entropy network-based methods for analysis of microarray data,
      and they indicate that TNF-alpha plays a direct role in Schwann cell-axon
      communication.

PMID- 19597152
TI  - Dating the emergence of pandemic influenza viruses.
AB  - Pandemic influenza viruses cause significant mortality in humans. In the 20th
      century, 3 influenza viruses caused major pandemics: the 1918 H1N1 virus, the
      1957 H2N2 virus, and the 1968 H3N2 virus. These pandemics were initiated by the
      introduction and successful adaptation of a novel hemagglutinin subtype to humans
      from an animal source, resulting in antigenic shift. Despite global concern
      regarding a new pandemic influenza, the emergence pathway of pandemic strains
      remains unknown. Here we estimated the evolutionary history and inferred date of
      introduction to humans of each of the genes for all 20th century pandemic
      influenza strains. Our results indicate that genetic components of the 1918 H1N1
      pandemic virus circulated in mammalian hosts, i.e., swine and humans, as early as
      1911 and was not likely to be a recently introduced avian virus. Phylogenetic
      relationships suggest that the A/Brevig Mission/1/1918 virus (BM/1918) was
      generated by reassortment between mammalian viruses and a previously circulating
      human strain, either in swine or, possibly, in humans. Furthermore, seasonal and
      classic swine H1N1 viruses were not derived directly from BM/1918, but their
      precursors co-circulated during the pandemic. Mean estimates of the time of most
      recent common ancestor also suggest that the H2N2 and H3N2 pandemic strains may
      have been generated through reassortment events in unknown mammalian hosts and
      involved multiple avian viruses preceding pandemic recognition. The possible
      generation of pandemic strains through a series of reassortment events in mammals
      over a period of years before pandemic recognition suggests that appropriate
      surveillance strategies for detection of precursor viruses may abort future
      pandemics.

PMID- 19597147
TI  - Genomewide SNP variation reveals relationships among landraces and modern
      varieties of rice.
AB  - Rice, the primary source of dietary calories for half of humanity, is the first
      crop plant for which a high-quality reference genome sequence from a single
      variety was produced. We used resequencing microarrays to interrogate 100 Mb of
      the unique fraction of the reference genome for 20 diverse varieties and
      landraces that capture the impressive genotypic and phenotypic diversity of
      domesticated rice. Here, we report the distribution of 160,000 nonredundant SNPs.
      Introgression patterns of shared SNPs revealed the breeding history and
      relationships among the 20 varieties; some introgressed regions are associated
      with agronomic traits that mark major milestones in rice improvement. These
      comprehensive SNP data provide a foundation for deep exploration of rice
      diversity and gene-trait relationships and their use for future rice improvement.

PMID- 19597154
TI  - Redefining the p53 response element.
AB  - The tumor suppressor p53 is a master transcriptional regulator that affects a
      diverse range of cellular events. Surprisingly, even with >100 validated p53
      response element (RE) sequences available, the effect of p53 binding on
      transcriptional behavior is seldom predictable and no functional rules have been
      described. Here, we report a systematic study on the role of specific nucleotides
      within the p53RE by using p21, a well-known target for p53 activation and
      contrasting it with Lasp1, a gene recently identified to be repressed by p53.
      Functional assays revealed a specific dinucleotide core combination within the
      CWWG motif of the p53RE to be the key factor that determines whether p53
      transcriptionally activates or represses a target gene. The triplet RRR and YYY
      sequences flanking the core CWWG motif were also shown to play an important role
      in modulating the transcriptional behavior of p53. With the establishment of a
      set of predictive rules, we were able to reassess 162 published p53REs and showed
      that the attributed function for 20/162 p53REs studied were in fact erroneous. A
      significant proportion of p53REs (39/162) were found to be repressive, which is
      substantially higher than what is currently thought. Hence this clearer
      definition of the transcriptional behavior of p53 interaction with its RE will
      provide better insight toward the understanding of its fundamental role in
      cellular networks.

PMID- 19597153
TI  - MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never
      smokers.
AB  - Fifteen percent of lung cancer cases occur in never-smokers and show
      characteristics that are molecularly and clinically distinct from those in
      smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are
      correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are
      more frequent in never-smoker lung cancers. In this study, microRNA (miRNA)
      expression profiling of 28 cases of never-smoker lung cancer identified
      aberrantly expressed miRNAs, which were much fewer than in lung cancers of
      smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and
      unidentified (e.g., down-regulated miR-138) in those smoker cases. The changes in
      expression of some of these miRNAs, including miR-21, were more remarkable in
      cases with EGFR mutations than in those without these mutations. A significant
      correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung
      carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478,
      suggest that the EGFR signaling is a pathway positively regulating miR-21
      expression. In the never-smoker-derived lung adenocarcinoma cell line H3255 with
      mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21
      enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell
      line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive
      effect with AG1478 but also induced apoptosis by itself. These results suggest
      that aberrantly increased expression of miR-21, which is enhanced further by the
      activated EGFR signaling pathway, plays a significant role in lung carcinogenesis
      in never-smokers, as well as in smokers, and is a potential therapeutic target in
      both EGFR-mutant and wild-type cases.

PMID- 19597155
TI  - Distinct opioid circuits determine the palatability and the desirability of
      rewarding events.
AB  - It generally is assumed that a common neural substrate mediates both the
      palatability and the reward value of nutritive events. However, recent evidence
      suggests this assumption may not be true. Whereas opioid circuitry in both the
      nucleus accumbens and ventral pallidum has been reported to mediate taste
      reactivity responses to palatable events, the assignment of reward or inventive
      value to goal-directed actions has been found to involve the basolateral
      amygdala. Here we found that, in rats, the neural processes mediating
      palatability and incentive value are indeed dissociable. Naloxone infused into
      either the ventral pallidum or nucleus accumbens shell blocked the increase in
      sucrose palatability induced by an increase in food deprivation without affecting
      the performance of sucrose-related actions. Conversely, naloxone infused into the
      basolateral amygdala blocked food deprivation-induced changes in sucrose-related
      actions without affecting sucrose palatability. This double dissociation of
      opioid-mediated changes in palatability and incentive value suggests that the
      role of endogenous opioids in reward processing does not depend on a single
      neural circuit. Rather, changes in palatability and in the incentive value
      assigned to rewarding events seem to be mediated by distinct neural processes.

PMID- 19597156
TI  - Legumes regulate Rhizobium bacteroid development and persistence by the supply of
      branched-chain amino acids.
AB  - One of the largest contributions to biologically available nitrogen comes from
      the reduction of N(2) to ammonia by rhizobia in symbiosis with legumes. Plants
      supply dicarboxylic acids as a carbon source to bacteroids, and in return they
      receive ammonia. However, metabolic exchange must be more complex, because
      effective N(2) fixation by Rhizobium leguminosarum bv viciae bacteroids requires
      either one of two broad-specificity amino acid ABC transporters (Aap and Bra). It
      was proposed that amino acids cycle between plant and bacteroids, but the model
      was unconstrained because of the broad solute specificity of Aap and Bra. Here,
      we constrain the specificity of Bra and ectopically express heterologous
      transporters to demonstrate that branched-chain amino acid (LIV) transport is
      essential for effective N(2) fixation. This dependence of bacteroids on the plant
      for LIV is not due to their known down-regulation of glutamate synthesis, because
      ectopic expression of glutamate dehydrogenase did not rescue effective N(2)
      fixation. Instead, the effect is specific to LIV and is accompanied by a major
      reduction in transcription and activity of LIV biosynthetic enzymes. Bacteroids
      become symbiotic auxotrophs for LIV and depend on the plant for their supply.
      Bacteroids with aap bra null mutations are reduced in number, smaller, and have a
      lower DNA content than wild type. Plants control LIV supply to bacteroids,
      regulating their development and persistence. This makes it a critical control
      point for regulation of symbiosis.

PMID- 19597159
TI  - Social inequalities in grip strength, physical function, and falls among
      community dwelling older men and women: findings from the Hertfordshire Cohort
      Study.
AB  - Objectives. To explore social inequalities in grip strength, SF-36 physical
      functioning (PF), and falls among older people. Methods. We analyzed data from
      3,225 men and women (age 59-73 years) who participated in the Hertfordshire
      Cohort Study, United Kingdom. Car availability and home ownership were used as
      markers of material deprivation. Results. A total of 6.4% of men (17.7% women)
      had no car and 19.3% of men (23.1% women) did not own their home. Having fewer
      cars was associated with lower grip and poorer PF among men and women (p < .001),
      and increased falls among men (p < .001). Not owning one's home was associated
      with lower grip in men and women (p < .001) and poorer PF in men (p < .001).
      Lower social class was associated with falls among women only (p = .01).
      Discussion. There are social inequalities in grip strength, PF, and falls among
      older people. Interventions should consider the contribution of social
      inequalities to the problem.

PMID- 19597157
TI  - A basal ganglia-forebrain circuit in the songbird biases motor output to avoid
      vocal errors.
AB  - In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for
      the learning and production of complex motor behaviors; however, the precise role
      of these circuits remains unknown. It has recently been shown that a basal
      ganglia-forebrain circuit in the songbird, which projects directly to vocal-motor
      circuitry, has a premotor function driving exploration necessary for vocal
      learning. It has also been hypothesized that this circuit, known as the anterior
      forebrain pathway (AFP), may generate an instructive signal that improves
      performance in the motor pathway. Here, we show that the output of the AFP
      directly implements a motor correction that reduces vocal errors. We use
      disruptive auditory feedback, contingent on song pitch, to induce learned changes
      in song structure over the course of hours and find that reversible inactivation
      of the output of the AFP produces an immediate regression of these learned
      changes. Thus, the AFP is involved in generating an error-reducing bias, which
      could increase the efficiency of vocal exploration and instruct synaptic changes
      in the motor pathway. We also find that learned changes in the song generated by
      the AFP are incorporated into the motor pathway within 1 day. Our observations
      support a view that basal ganglia-related circuits directly implement behavioral
      adaptations that minimize errors and subsequently stabilize these adaptations by
      training premotor cortical areas.

PMID- 19597158
TI  - Quantification of nano-scale intermembrane contact areas by using fluorescence
      resonance energy transfer.
AB  - Nanometer-scale intermembrane contact areas (CAs) formed between single small
      unilamellar lipid vesicles (SUVs) and planar supported lipid bilayers are
      quantified by measuring fluorescence resonance energy transfer (FRET) between a
      homogenous layer of donor fluorophores labeling the supported bilayer and
      acceptor fluorophores labeling the SUVs. The smallest CAs detected in our setup
      between biotinylated SUVs and dense monolayers of streptavidin were approximately
      20 nm in radius. Deformation of SUVs is revealed by comparing the quenching of
      the donors to calculations of FRET between a perfectly spherical shell and a flat
      surface containing complementary fluorophores. These results confirmed the
      theoretical prediction that the degree of deformation scales with the SUV
      diameter. The size of the CA can be controlled experimentally by conjugating
      polyethylene glycol polymers to the SUV or the surface and thereby modulating the
      interfacial energy of adhesion. In this manner, we could achieve secure
      immobilization of SUVs under conditions of minimal deformation. Finally, we
      demonstrate that kinetic measurements of CA, at constant adhesion, can be used to
      record in real-time quantitative changes in the bilayer tension of a nano-scale
      lipid membrane system.

PMID- 19597160
TI  - Help-seeking behaviors and reasons for help seeking reported by a representative
      sample of women victims of intimate partner violence in New Zealand.
AB  - Efforts to understand and support the process of help seeking by victims of
      intimate partner violence are of considerable urgency if we are to design systems
      and responses that are capable of actively and appropriately meeting the needs of
      victims. Using data from the New Zealand Violence Against Women Study, which drew
      from a representative general population sample of women aged 18 to 64 years, the
      authors report on the help-seeking behaviors of the women who had ever in their
      lifetime experienced physical and/or sexual violence by an intimate partner (n =
      956). More than 75% of respondents reported that they had told someone about the
      violence, indicating that it is not necessarily a "secret and private" problem.
      However, more than 40% of women indicated that no one had helped them. Informal
      sources of support (family and friends) were most frequently told about the
      violence but not all provided helpful responses. Fewer women told formal sources
      of help such as police, health care providers, and not all provided helpful
      responses. Women's reasons for seeking help and for leaving violent relationships
      were similar and included "could not endure more," being badly injured, fear or
      threat of death, and concern for children. Women's reasons for staying in or
      returning to violent relationships included perception of the violence as
      "normal/not serious," her emotional investment in the relationship, or staying
      for the sake of the children. The findings suggest that broader community
      outreach is required to ensure that family and friends are able to provide
      appropriate support for women in abusive relationships who are seeking help.
      Continued improvement in institutional responses is also required.

PMID- 19597161
TI  - Phylogenetic-signal dissection of nuclear housekeeping genes supports the
      paraphyly of sponges and the monophyly of Eumetazoa.
AB  - The relationships at the base of the metazoan tree have been difficult to
      robustly resolve, and there are several different hypotheses regarding the
      interrelationships among sponges, cnidarians, ctenophores, placozoans, and
      bilaterians, with each hypothesis having different implications for the body plan
      of the last common ancestor of animals and the paleoecology of the late
      Precambrian. We have sequenced seven nuclear housekeeping genes from 17 new
      sponges, bringing the total to 29 species analyzed, including multiple
      representatives of the Demospongiae, Calcarea, Hexactinellida, and
      Homoscleromorpha, and analyzed a data set also including six nonmetazoan
      outgroups and 36 eumetazoans using a variety of phylogenetic methods and
      evolutionary models. We used leaf stability to identify rogue taxa and
      investigate their effect on the support of the nodes in our trees, and we
      identified clades most likely to represent phylogenetic artifacts through the
      comparison of trees derived using different methods (and models) and through site
      stripping analyses. Further, we investigated compositional heterogeneity and
      tested whether amino acid composition bias affected our results. Finally, we used
      Bayes factors to compare our results against previously published phylogenies.
      All our maximum likelihood (ML) and Bayesian analyses find sponges to be
      paraphyletic, with all analyses finding three extant paraphyletic sponge
      lineages, Demospongiae plus Hexactinellida, Calcarea, and Homoscleromorpha. All
      but one of our ML and Bayesian analyses support the monophyly of Eumetazoa (here
      Cnidaria + Bilateria) and a sister group relationship between Placozoa (here
      Trichoplax adhaerens) and Eumetazoa. Bayes factors invariably provide decisive
      support in favor of poriferan paraphyly when compared against either a sister
      group relationship between Porifera and Cnidaria or with a monophyletic Porifera
      with respect to a monophyletic Eumetazoa. Although we were able to recover sponge
      monophyly using our data set, this was only possible under unrealistic
      evolutionary models, if poorly performing phylogenetic methods were used, or in
      situations where the potential for the generation of tree reconstruction
      artifacts was artificially exacerbated. Everything considered, our data set does
      not provide any support for a monophyletic Diploblastica (here Placozoa +
      Cnidaria + Porifera) and suggests that a monophyletic Porifera may be better seen
      as a phylogenetic artifact.

PMID- 19597162
TI  - Structural determinants of protein evolution are context-sensitive at the residue
      level.
AB  - Structural properties of a protein residue's microenvironment have long been
      implicated as agents of selective constraint. Although these properties are
      inherently quantitative, structure-based studies of protein evolution tend to
      rely upon coarse distinctions between "surface" and "buried" residues and between
      "interfacial" and "noninterfacial" residues. Using homology-mapped yeast protein
      structures, we explore the relationships between residue evolution and continuous
      structural properties of the residue microenvironment, including solvent
      accessibility, density and distribution of residue-residue contacts, and burial
      depth. We confirm the role of solvent exposure as a major structural determinant
      of residue evolution and also identify a weak secondary effect arising from
      packing density. The relationship between solvent exposure and evolutionary rate
      (d(N)/d(S)) is found to be strong, positive, and linear. This reinforces the
      notion that residue burial is a continuous property with quantitative fitness
      implications. Next, we demonstrate systematic variation in residue-level
      structure-evolution relationships resulting from changes in global physical and
      biological contexts. We find that increasing protein-core size yields a more
      rapid relaxation of selective constraint as solvent exposure increases, although
      solvent-excluded residues remain similarly constrained. Finally, we analyze the
      selective constraint in protein-protein interfaces, revealing two fundamentally
      different yet separable components: continuous structural constraint that scales
      with total residue burial and a more surprising fixed functional constraint that
      accompanies any degree of interface involvement. These discoveries serve to
      elucidate and unite structure-evolution relationships at the residue and whole
      protein levels.

PMID- 19597163
TI  - Genes within genes: multiple LAGLIDADG homing endonucleases target the ribosomal
      protein S3 gene encoded within an rnl group I intron of Ophiostoma and related
      taxa.
AB  - In some ascomycete fungi, ribosomal protein S3 (Rps3) is encoded within a group I
      intron (mL2449) that is inserted in the U11 region of the mitochondrial large
      subunit rDNA (rnl) gene. Previous characterization of the mL2449 intron in
      strains of Ophiostoma novo-ulmi subspecies americana (Dutch Elm Disease) revealed
      a complex genes-within-genes arrangement whereby a LAGLIDADG homing endonuclease
      gene (HEG) is inserted into the RPS3 gene near the 3' terminus, creating a hybrid
      Rps3-LAGLIDADG fusion protein. Here, we examined 119 additional strains of
      Ophiostoma and related taxa representing 85 different species by a polymerase
      chain reaction- based survey and detected both short (approximately 1.6 kb) and
      long (>2.2 kb) versions of the mL2449 intron in 88 and 31 strains, respectively.
      Among the long versions encountered, 21 were sequenced, revealing the presence of
      either intact or degenerated HEG-coding regions inserted within the RPS3 gene.
      Surprisingly, we identified two new HEG insertion sites in RPS3; one near the
      original C-terminal insertion site and one near the N-terminus of RPS3. In all
      instances, the HEGs are fused in-frame with the RPS3-coding sequences to create
      fusion proteins. However, comparative sequence analysis showed that upon
      insertion, the HEGs displaced a portion of the RPS3-coding region. Remarkably,
      the displaced RPS3-coding segments are duplicated and fused in-frame to the 3'
      end of RPS3, restoring a full-length RPS3 gene. We cloned and expressed the
      LAGLIDADG portion of two Rps3-HEG fusions, and showed that I-OnuI and I-LtrI
      generate 4 nucleotide (nt), 3' overhangs, and cleave at or 1 nt upstream of the
      HEG insertion site, respectively. Collectively, our data indicate that RPS3 genes
      are a refuge for distinct types of LAGLIDADG HEGs that are defined by the
      presence of duplicated segments of the host gene that restore the RPS3 gene, thus
      minimizing the impact of the HEG insertion on Rps3 function.

PMID- 19597164
TI  - Annals transitions.

PMID- 19597166
TI  - Call for papers: clinical research.

PMID- 19597165
TI  - The paradox of primary care.

PMID- 19597167
TI  - Elements of the patient-centered medical home in family practices in Virginia.
AB  - PURPOSE: The patient-centered medical home (PCMH) is a widely accepted theory of
      a practice model to improve quality of care, patient satisfaction, and access to
      primary care services. This study explores existing elements of the PCMH and
      characteristics of family practices in Virginia. METHOD: We developed and
      administered a survey questionnaire to capture information on practice
      characteristics and PCMH elements. We randomly sampled 700 family medicine
      offices in Virginia from a population of practices derived from the Virginia
      Board of Medicine Practitioner Information Database. We used a mixed-mode survey,
      allowing practices in the sample to respond by mail or Internet or at a regional
      family medicine conference. RESULTS: The survey resulted in a response rate of
      56%, with 342 office locations participating in the study. Most practices
      reported continuity-of-care processes (87%) and clinical guidelines (77%). Fewer
      reported use of patient surveys (48%), electronic medical record for internal
      coordination (38%), community linkages for care (31%), and clinical performance
      measurement (28%). A small number reported patient registries for multiple
      diseases (19%). Very few practices exhibited all elements outlined in the PCMH
      model (1%). Practice size (number of physicians) is significantly related to PCMH
      model alignment. CONCLUSIONS: Most family practices in Virginia exhibit some
      elements of the PCMH model. Full implementation of the PCMH model is low.
      Baseline information on practice characteristics, prevalence of PCMH, and
      challenges of small practices should be considered in guiding efforts, evaluating
      progress, and developing policies for care model reform.

PMID- 19597168
TI  - Managing chronic disease in ontario primary care: the impact of organizational
      factors.
AB  - PURPOSE: New approaches to chronic disease management emphasize the need to
      improve the delivery of primary care services to meet the needs of chronically
      ill patients. This study (1) assessed whether chronic disease management differed
      among 4 models of primary health care delivery and (2) identified which practice
      organizational factors were independently associated with high-quality care.
      METHODS: We undertook a cross-sectional survey with nested qualitative case
      studies (2 practices per model) in 137 randomly selected primary care practices
      from 4 delivery models in Ontario Canada: fee for service, capitation, blended
      payment, and community health centers (CHCs). Practice and clinician surveys were
      based on the Primary Care Assessment Tool. A chart audit assessed evidence-based
      care delivery for patients with diabetes, congestive heart failure, and coronary
      artery disease. Intermediate outcomes were calculated for patients with diabetes
      and hypertension. Multiple linear regression identified those organizational
      factors independently associated with chronic disease management. RESULTS:
      Chronic disease management was superior in CHCs. Clinicians in CHCs found it
      easier than those in the other models to promote high-quality care through longer
      consultations and interprofessional collaboration. Across the whole sample and
      independent of model, high-quality chronic disease management was associated with
      the presence of a nurse-practitioner. It was also associated with lower patient
      family physician ratios and when practices had 4 or fewer full-time-equivalent
      family physicians. CONCLUSIONS: The study adds to the literature supporting the
      value of nurse-practitioners within primary care teams and validates the
      contributions of Ontario's CHCs. Our observation that quality of care decreased
      in larger, busier practices suggests that moves toward larger practices and
      greater patient-physician ratios may have unanticipated negative effects on
      processes of care quality.

PMID- 19597170
TI  - Does diabetes double the risk of depression?
AB  - PURPOSE: In this study, we compared the rate of depression diagnoses in adults
      with and without diabetes mellitus, while carefully controlling for number of
      primary care visits. METHODS: We matched adults with incident diabetes (n =
      2,932) or prevalent diabetes (n = 14,144) to nondiabetic control patients based
      on (1) age and sex, or (2) age, sex, and number of outpatient primary care
      visits. Logistic regression analysis was used to assess the association between
      various predictors and a diagnosis of depression in each diabetes cohort relative
      to matched nondiabetic control patients. RESULTS: With matching for age and sex
      alone, patients with prevalent diabetes having few primary care visits were
      significantly more likely to have a new depression diagnosis than matched control
      patients (odds ratio [OR] = 1.46, 95% confidence interval [CI], 1.19-1.80), but
      this relationship diminished when patients made more than 10 primary care visits
      (OR = 0.95, 95% CI, 0.77-1.17). With additional matching for number of primary
      care visits, patients with prevalent diabetes mellitus with few primary care
      visits were more likely to have a new diagnosis of depression than those in
      control group (OR = 1.32, 95% CI, 1.07-1.63), but this relationship diminished
      and reversed when patients made more than 4 primary care visits (OR = 0.99, 95%
      CI, 0.80-1.23). Similar results were observed in the subset of patients with
      incident diabetes and their matched control patients. CONCLUSIONS: Patients with
      diabetes have little or no increase in the risk of a new diagnosis of depression
      relative to nondiabetic patients when analyses carefully control for the number
      of outpatient visits. Studies showing such an association may have inadequately
      adjusted for comorbidity or for exposure to the medical care system.

PMID- 19597169
TI  - Home-based, peer-led chronic illness self-management training: findings from a 1
      year randomized controlled trial.
AB  - PURPOSE: Studies suggest peer-led self-management training improves chronic
      illness outcomes by enhancing illness management self-efficacy. Limitations of
      most studies, however, include use of multiple outcome measures without
      predesignated primary outcomes and lack of randomized follow-up beyond 6 months.
      We conducted a 1-year randomized controlled trial of Homing in on Health (HIOH),
      a Chronic Disease Self-Management Program variant, addressing these limitations.
      METHODS: We randomized outpatients (N = 415) aged 40 years and older and who had
      1 or more of 6 common chronic illnesses, plus functional impairment, to HIOH
      delivered in homes or by telephone for 6 weeks or to usual care. Primary outcomes
      were the Medical Outcomes Study 36-ltem short-form health survey's physical
      component (PCS-36) and mental component (MCS-36) summary scores. Secondary
      outcomes included the EuroQol EQ-5D and visual analog scale (EQ VAS),
      hospitalizations, and health care expenditures. RESULTS: Compared with usual
      care, HIOH delivered in the home led to significantly higher illness management
      self-efficacy at 6 weeks (effect size = 0.27; 95% CI, 0.10-0.43) and at 6 months
      (0.17; 95% CI, 0.01-0.33), but not at 1 year. In-home HIOH had no significant
      effects on PCS-36 or MCS-36 scores and led to improvement in only 1 secondary
      outcome, the EQ VAS (1-year effect size = 0.40; CI, 0.14-0.66). HIOH delivered by
      telephone had no significant effects on any outcomes. CONCLUSIONS: Despite
      leading to improvements in self-efficacy comparable to those in other CDSMP
      studies, in-home HIOH had a limited sustained effect on only 1 secondary health
      status measure and no effect on utilization. These findings question the cost
      effectiveness of peer-led illness self-management training from the health system
      perspective.

PMID- 19597171
TI  - Promise of professionalism: personal mission statements among a national cohort
      of medical students.
AB  - PURPOSE: While historic medical oaths and numerous contemporary medical
      organizations offer guidelines for professionalism, the nature of the
      professional aspirations, commitments, and values of current medical students is
      not well known. We sought to provide a thematic catalogue of individual mission
      statements written by medical students nationally. METHODS: In the Healer's Art
      elective course, students write a personal mission statement about their highest
      professional values. In 2006-2007, we randomly selected 100 student mission
      statements from 10 representative schools nationally. Three researchers coded
      content using a team-based qualitative approach and categorized the codes into
      major themes. Student mission statements were compared with classic medical oaths
      and contemporary professionalism guidelines. RESULTS: The mission statements were
      similar across different schools. Three major themes emerged, comprised of codes
      identified in 20% or more of the mission statements. The first theme,
      professional skills, includes dealing with the negatives of training, listening
      and empathy, growth and development. The second theme, personal qualities,
      includes wholeness, humility, and constancy/perfectionism. The third theme, scope
      of professional practice, includes physician relationships, positive emotions,
      healing, service, spirituality, and balance. Unlike the content of classic oaths
      and contemporary professionalism statements, the students' statements dealt with
      fears, personal-professional balance, love, nonhierachical relationships, self
      care, healing, and awe as key to being a physician. CONCLUSIONS: In their
      personal mission statements, this national cohort of medical students described
      an expanded view of physicianhood that includes such elements as presence, love,
      and awe. Medical school curricula may require adaptation to support the personal
      aspirations of those now entering the profession.

PMID- 19597172
TI  - Management of test results in family medicine offices.
AB  - PURPOSE: We wanted to explore test results management systems in family medicine
      offices and to delineate the components of quality in results management.
      METHODS: Using a multimethod protocol, we intensively studied 4 purposefully
      chosen family medicine offices using observations, interviews, and surveys. Data
      analysis consisted of iterative qualitative analysis, descriptive frequencies,
      and individual case studies, followed by a comparative case analysis. We assessed
      the quality of results management at each practice by both the presence of and
      adherence to systemwide practices for each results management step, as well as
      outcomes from chart reviews, patient surveys, and interview and observation
      notes. RESULTS: We found variability between offices in how they performed the
      tasks for each of the specific steps of results management. No office
      consistently had or adhered to office-wide results management practices, and only
      2 offices had written protocols or procedures for any results management steps.
      Whereas most patients surveyed acknowledged receiving their test results (87% to
      100%), a far smaller proportion of patient charts documented patient notification
      (58% to 85%), clinician response to the result (47% to 84%), and follow-up for
      abnormal results (28% to 55%). We found 2 themes that emerged as factors of
      importance in assessing test results management quality: safety awareness-a
      leadership focus and communication that occurs around quality and safety,
      teamwork in the office, and the presence of appropriate policies and procedures;
      and technological adoption-the presence of an electronic health record, digital
      connections between the office and testing facilities, use of technology to
      facilitate patient communication, and the presence of forcing functions (built-in
      safeguards and requirements). CONCLUSION: Understanding the components of safety
      awareness and technological adoption can assist family medicine offices in
      evaluating their own results management processes and help them design systems
      that can lead to higher quality care.

PMID- 19597173
TI  - Musculoskeletal problems in overweight and obese children.
AB  - PURPOSE: The obesity epidemic in children is spreading at alarming rates. Because
      musculoskeletal problems can influence physical activity, we compared the
      frequency of musculoskeletal problems in overweight and obese children with that
      in normal-weight children. METHODS: We performed a cross-sectional database and
      face-to-face interview study that included 2,459 children aged 2 to 17 years from
      Dutch family practices. We collected data on self-reported height and weight
      (body mass index), self-reported musculoskeletal problems in the 2 weeks before
      the interview, number of family physician consultations for musculoskeletal
      problems in 1 year, and age (2 age-groups were analyzed: 2 to 11 years and 12 to
      17 years, because of the proxy interview in the youngest age-group). We
      calculated the odds ratio (OR) and 95% confidence interval (CI) for
      musculoskeletal problems in overweight and obese children, compared with normal
      weight children. RESULTS: Overweight and obese children in both age-groups (2 to
      11 years and 12 to 17 years) reported significantly more musculoskeletal problems
      (OR = 1.86; 95% CI, 1.18-2.93; and OR = 1.69; 95% CI, 1.08-2.65, respectively)
      than normal-weight children. The total group of children who were overweight or
      obese reported more lower extremity problems than did the normal-weight children
      (OR = 1.62; 95% CI, 1.09-2.41); furthermore, they reported more ankle and foot
      problems than children who were of normal weight (OR = 1.92; 95% CI, 1.15-3.20).
      Overweight and obese children aged 12 to 17 years consulted their family
      physicians more often with lower extremity problems than did the normal-weight
      children (OR = 1.92; 95% CI, 1.05-3.51). CONCLUSION: This study shows that
      overweight and obese children more frequently experience musculoskeletal problems
      than do normal-weight children.

PMID- 19597174
TI  - Defining comorbidity: implications for understanding health and health services.
AB  - Comorbidity is associated with worse health outcomes, more complex clinical
      management, and increased health care costs. There is no agreement, however, on
      the meaning of the term, and related constructs, such as multimorbidity,
      morbidity burden, and patient complexity, are not well conceptualized. In this
      article, we review definitions of comorbidity and their relationship to related
      constructs. We show that the value of a given construct lies in its ability to
      explain a particular phenomenon of interest within the domains of (1) clinical
      care, (2) epidemiology, or (3) health services planning and financing. Mechanisms
      that may underlie the coexistence of 2 or more conditions in a patient (direct
      causation, associated risk factors, heterogeneity, independence) are examined,
      and the implications for clinical care considered. We conclude that the more
      precise use of constructs, as proposed in this article, would lead to improved
      research into the phenomenon of ill health in clinical care, epidemiology, and
      health services.

PMID- 19597175
TI  - Importance of evidence grading for guideline implementation: the example of
      asthma.
AB  - The goal of evidence-based clinical guidelines is to improve the value of health
      care by recommending treatments with favorable benefit/harm ratios. Achieving
      this goal requires use of evidence-grading systems that explicitly address
      strength of evidence in terms of external validity (generalizability), internal
      validity, and patient-oriented outcomes. To be clinically useful, guidelines
      should also incorporate patient preferences, particularly when evidence is weak.
      The National Heart, Lung and Blood Institute recently published Expert Panel
      Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR-3). This
      special report addresses the extent to which current guidelines adhere to the
      principles enunciated above by using EPR-3 as the prime example. EPR-3 used an
      unconventional evidence-grading system that emphasized precision and consistency
      (statistical significance, large sample sizes, and/or consistency of results) at
      the expense of patient-oriented outcomes and generalizability (applicability to
      the general population). EPR-3 did not report information on numbers needed to
      treat or numbers needed to harm, which are useful in eliciting patient
      preferences via shared decision making. Asthma guidelines (and others) are
      limited by lack of a generalizable research base, 3 awed evidence grading, and
      lack of attention to patient preferences. An evidence-grading system based on
      applicable populations, patient-oriented outcomes, and shared decision making
      might improve physician and patient guideline adherence and improve asthma
      outcomes.

PMID- 19597176
TI  - fmCASES: Collaborative Development of Online Cases to Address Educational Needs.

PMID- 19597177
TI  - Vision, voice, leadership: ADFM's next phase.

PMID- 19597178
TI  - Advocacy: the time is now.

PMID- 19597179
TI  - Academy launches comprehensive patient-centered medical home resources.

PMID- 19597180
TI  - NAPCRG congratulates AAFP national research network on its 10th anniversary.

PMID- 19597181
TI  - American board of family medicine in-training examination.

PMID- 19597182
TI  - Cytokine-mediated increases in fetal hemoglobin are associated with globin gene
      histone modification and transcription factor reprogramming.
AB  - Therapeutic regulation of globin genes is a primary goal of translational
      research aimed toward hemoglobinopathies. Signal transduction was used to
      identify chromatin modifications and transcription factor expression patterns
      that are associated with globin gene regulation. Histone modification and
      transcriptome profiling were performed using adult primary CD34(+) cells cultured
      with cytokine combinations that produced low versus high levels of gamma-globin
      mRNA and fetal hemoglobin (HbF). Embryonic, fetal, and adult globin transcript
      and protein expression patterns were determined for comparison. Chromatin
      immunoprecipitation assays revealed RNA polymerase II occupancy and histone tail
      modifications consistent with transcriptional activation only in the high-HbF
      culture condition. Transcriptome profiling studies demonstrated reproducible
      changes in expression of nuclear transcription factors associated with high HbF.
      Among the 13 genes that demonstrated differential transcript levels, 8
      demonstrated nuclear protein expression levels that were significantly changed by
      cytokine signal transduction. Five of the 8 genes are recognized regulators of
      erythropoiesis or globin genes (MAFF, ID2, HHEX, SOX6, and EGR1). Thus, cytokine
      mediated signal transduction in adult erythroid cells causes significant changes
      in the pattern of globin gene and protein expression that are associated with
      distinct histone modifications as well as nuclear reprogramming of erythroid
      transcription factors.

PMID- 19597183
TI  - B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative
      disorders.
AB  - Stromal elements present within the tumor microenvironment may suppress host
      immunity and promote the growth of malignant lymphocytes in B cell-derived non
      Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's
      role in T cell-derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of
      costimulatory/co-inhibitory ligands expressed by both malignant cells and stromal
      cells within the tumor microenvironment, has emerged as an important immune
      modulator capable of suppressing host immunity. Therefore, B7-H1 expression and
      function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was
      expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor
      microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and
      promote the induction of FoxP3(+) regulatory T cells. Collectively, the data
      presented provide the first evidence implicating B7-H1 in the suppression of host
      immunity in T-cell lymphoproliferative disorders and suggest that the targeting
      of B7-H1 may represent a novel therapeutic approach.

PMID- 19597184
TI  - Lymphomas with concurrent BCL2 and MYC translocations: the critical factors
      associated with survival.
AB  - BCL2 and MYC are oncogenes commonly deregulated in lymphomas. Concurrent BCL2 and
      MYC translocations (BCL2(+)/MYC(+)) were identified in 54 samples by karyotype
      and/or fluorescence in situ hybridization with the aim of correlating clinical
      and cytogenetic characteristics to overall survival. BCL2(+)/MYC(+) lymphomas
      were diagnosed as B-cell lymphoma unclassifiable (BCLU; n = 36) with features
      intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL);
      DLBCL (n = 17), or follicular lymphoma (n = 1). Despite the presence of a
      t(14;18), 5 cases were BCL2 protein-negative. Nonimmunoglobulin gene/MYC (non
      IG/MYC) translocations occurred in 24 of 54 cases (44%) and were highly
      associated with DLBCL morphology (P < .001). Over a median follow-up of 5.3
      years, 6 patients remained in remission and 32 died within 6 months of the MYC(+)
      rearrangement, irrespective of whether MYC(+) occurred at diagnosis (31 of 54) or
      transformation (23 of 54; P = .53). A non-IG/MYC translocation partner, absent
      BCL2 protein expression and treatment with rituximab-based chemotherapy, were
      associated with a more favorable outcome, but a low International Prognostic
      Index score and DLBCL morphology were independent predictors of overall survival.
      A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive
      lymphomas may identify a group of high-risk patients who may benefit from
      chemotherapeutic regimens that include rituximab and/or BCL2-targeted therapy.

PMID- 19597185
TI  - The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients
      and its activation affects myeloma bone disease and tumor growth.
AB  - Myeloma bone disease is caused by uncoupling of osteoclastic bone resorption and
      osteoblastic bone formation. Bidirectional signaling between the cell-surface
      ligand ephrinB2 and its receptor, EphB4, is involved in the coupling of
      osteoblastogenesis and osteoclastogenesis and in angiogenesis. EphrinB2 and EphB4
      expression in mesenchymal stem cells (MSCs) from myeloma patients and in bone
      cells in myelomatous bones was lower than in healthy counterparts. Wnt3a induced
      up-regulation of EphB4 in patient MSCs. Myeloma cells reduced expression of these
      genes in MSCs, whereas in vivo myeloma cell-conditioned media reduced EphB4
      expression in bone. In osteoclast precursors, EphB4-Fc induced ephrinB2
      phosphorylation with subsequent inhibition of NFATc1 and differentiation. In
      MSCs, EphB4-Fc did not induce ephrinB2 phosphorylation, whereas ephrinB2-Fc
      induced EphB4 phosphorylation and osteogenic differentiation. EphB4-Fc treatment
      of myelomatous SCID-hu mice inhibited myeloma growth, osteoclastosis, and
      angiogenesis and stimulated osteoblastogenesis and bone formation, whereas
      ephrinB2-Fc stimulated angiogenesis, osteoblastogenesis, and bone formation but
      had no effect on osteoclastogenesis and myeloma growth. These chimeric proteins
      had similar effects on normal bone. Myeloma cells expressed low to undetectable
      ephrinB2 and EphB4 and did not respond to the chimeric proteins. The
      ephrinB2/EphB4 axis is dysregulated in MM, and its activation by EphB4-Fc
      inhibits myeloma growth and bone disease.

PMID- 19597187
TI  - Ethics and advance care planning in a culturally diverse society.
AB  - Emerging international research suggests that in multicultural countries, such as
      Australia and the United States, there are significant disparities in end-of-life
      care planning and decision making by people of minority ethnic backgrounds
      compared with members of mainstream English-speaking background populations.
      Despite a growing interest in the profound influence of culture and ethnicity on
      patient choices in end-of-life care, and the limited uptake of advance care plans
      and advance directives by ethnic minority groups in mainstream health care
      contexts, there has been curiously little attention given to cross-cultural
      considerations in advance care planning and end-of-life care. Also overlooked are
      the possible implications of cross-cultural considerations for nurses, policy
      makers, and others at the forefront of planning and providing end-of-life care to
      people of diverse cultural and language backgrounds. An important aim of this
      article is to redress this oversight.

PMID- 19597186
TI  - Correlates of heavy smoking among alcohol-using methadone maintenance clients.
AB  - This cross-sectional study examines predictors of heavy smoking among 256 male
      and female methadone maintenance therapy (MMT) clients from five MMT clinics in
      the Los Angeles area. The authors find that women report lower rates of heavy
      smoking than men (47% vs. 54%, respectively), in concordance with current
      literature pointing to gender differences in smoking behaviors. In particular,
      men who report heavy drinking, fair or poor health, and recent heroin use are
      more likely to report heavy smoking compared with men not reporting these
      factors. Women who report recent heroin use, a lifetime history of sex trade, and
      who have been ill enough to require a blood transfusion also have greater odds of
      reporting heavy cigarette smoking. Findings from this study may aid not only in
      designing gender-based smoking cessation programs for MMT clients but also in
      addressing the gender-based issues related to smoking in such a population.

PMID- 19597188
TI  - Intestinal redox status of major intracellular thiols in a rat model of chronic
      alcohol consumption.
AB  - BACKGROUND: Alcohol consumption is associated with oxidative stress in multiple
      tissues in vivo, yet the effect of chronic alcohol intake on intestinal redox
      state has received little attention. In this study, we investigated the redox
      status of 2 major intracellular redox regulating couples: glutathione
      (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) in a rat
      model of chronic alcohol ingestion. METHODS: Sprague-Dawley rats were fed the
      liquid Lieber-DeCarli diet consisting of 36% ethanol of total calories for 6
      weeks. Control rats were pair-fed with an isocaloric, ethanol-free liquid diet.
      Defined mucosal samples from the jejunum, ileum, and colon were obtained and
      analyzed by high-performance liquid chromatography (HPLC) for GSH and Cys pool
      redox status. Mucosal free malondialdehyde (MDA) was measured as an indicator of
      lipid peroxidation. RESULTS: In the ethanol-fed rats, Cys and mixed disulfide
      (GSH-Cys) were significantly decreased in all 3 segments of intestinal mucosa.
      Free MDA was increased in jejunal but not in ileal or colonic mucosa. Chronic
      ethanol ingestion significantly increased mucosal GSH concentration in
      association with a more reducing GSH/GSSG redox potential in the jejunum, but
      these indices were unchanged in the ileum. In the colon, chronic ethanol
      ingestion increased oxidant stress as suggested by decreased GSH and oxidized
      GSH/GSSG redox potential. CONCLUSIONS: Chronic alcohol intake differentially
      alters the mucosal redox status in proximal to distal intestinal segments in
      rats. Such changes may reflect different adaptability of these intestinal
      segments to the oxidative stress challenge induced by chronic ethanol ingestion.

PMID- 19597189
TI  - Synthesis, calorimetric studies, and crystal structures of N, O
      diacylethanolamines with matched chains.
AB  - Recent studies show that N-, O-diacylethanolamines (DAEs) can be derived by the O
      acylation of N-acylethanolamines (NAEs) under physiological conditions. Because
      the content of NAEs in a variety of organisms increases in response to stress, it
      is likely that DAEs may also be present in biomembranes. In view of this, a
      homologous series of DAEs with matched acyl chains (n = 10-20) have been
      synthesized and characterized. Transition enthalpies and entropies obtained from
      differential scanning calorimetry show that dry DAEs with even and odd acyl
      chains independently exhibit linear dependence on the chainlength. Linear least
      squares analyses yielded incremental values contributed by each methylene group
      to the transition enthalpy and entropy and the corresponding end contributions. N
      , O-Didecanoylethanolamine (DDEA), N-, O-dilauroylethanolamine (DLEA), and N-, O
      dimyristoylethanolamine (DMEA) crystallized in the orthorhombic space group
      Pbc(21) with four symmetry-related molecules in the unit cell. Single-crystal X
      ray diffraction studies show that DDEA, DLEA, and DMEA are isostructural and
      adopt an L-shaped structure with the N-acyl chain and the central ethanolamine
      moiety being essentially identical to the structure of N-acylethanolamines,
      whereas the O-acyl chain is linear with all-trans conformation. In all three
      DAEs, the lipid molecules are organized in a bilayer fashion wherein the N-acyl
      and O-acyl chains from adjacent layers oppose each other.

PMID- 19597191
TI  - The devilish details of delivering on global health.

PMID- 19597193
TI  - A global subsidy: key to affordable drugs for malaria?
AB  - The global fight against malaria has been continually challenged by poor access
      to affordable, effective medicine. Growing resistance to chloroquine, the
      traditional treatment, has worsened the situation. Artemisinins, the successor
      therapy to chloroquine, are at least ten times more costly than the older drug.
      In developing countries, most malaria medicines are purchased in the private
      sector, where traditional aid mechanisms do not reach. So a new aid approach was
      needed. The Affordable Medicines Facility-malaria (AMFm) will efficiently supply
      publicly subsidized drugs to meet public- and private-sector demand in malaria
      endemic countries. If artemisinins are priced more competitively, resistance to
      them will be delayed.

PMID- 19597194
TI  - Creating access to health technologies in poor countries.
AB  - Many people in developing countries lack access to health technologies. We
      present seven findings about processes that shape access, based on analysis of
      six case histories: praziquantel to treat schistosomiasis (a parasitic worm
      disease), hepatitis B vaccine, the Norplant contraceptive, malaria rapid
      diagnostic tests, vaccine vial monitors, and the female condom. Each case study
      is assessed with a comprehensive framework that examines the effects of
      architecture, availability, affordability, and adoption on creating access. The
      analysis shows that access to health technology in poor countries is difficult to
      achieve because of multiple obstacles, but it can be created under certain
      conditions.

PMID- 19597195
TI  - Improving health r&d financing for developing countries: a menu of innovative
      policy options.
AB  - New drugs, vaccines, and diagnostics for the diseases of the developing world
      could save millions of lives and prevent enormous suffering and economic loss.
      Despite substantial new funding from the Gates Foundation and other donors,
      financing for the development of these new health technologies remains
      inadequate. New approaches are needed to generate more resources, make funding
      more stable and flexible, and further engage the expertise of the pharmaceutical
      industry. Several new financing mechanisms have been launched recently, and
      others are being proposed. This paper summarizes some of the most promising new
      ideas and offers a framework for evaluating them.

PMID- 19597190
TI  - In vitro grown human ovarian follicles from cancer patients support oocyte
      growth.
AB  - BACKGROUND: Young female adult and adolescent cancer patients facing life
      preserving but fertility-threatening chemo- or radiation-therapy are increasingly
      seeking options to protect their reproductive potential. Ovarian tissue
      cryopreservation with transplantation is a promising technique to safeguard
      fertility in cancer patients. However, this method may risk re-introduction of
      the original cancer to the survivor of the disease. Thus, developing a method for
      in vitro growth of immature follicles may provide a method for fertility
      restoration in the future. METHODS: Human secondary follicles were isolated from
      ovarian tissues obtained from cancer patients and grown in vitro within a bio
      engineered culture system for 30 days. RESULTS: Human ovarian follicles became
      steroidogenically active, and developed from the early secondary to antral stage
      in vitro. The follicles contained healthy, growing oocytes that were connected by
      transzonal projections between the somatic cells and oocyte. CONCLUSIONS: Our
      data support the notion that human follicle development can be achieved in vitro
      in a bio-engineered culture system. More studies are required to investigate
      whether the fully sized oocytes obtained from in vitro grown follicle are
      competent to resume meiosis and be fertilized.

PMID- 19597196
TI  - Pathways of health technology diffusion: the United States and low-income
      countries.
AB  - In the United States, the complex process of getting health care technologies
      into practice takes place in a competitive health system that is driven by
      technological innovation. Federal, state, and local governments' roles in the
      diffusion process are limited. In low-income countries, where competitive markets
      are not as prominent, diffusing medical innovations requires an alternative
      understanding of how new technologies are adopted. This paper describes how, in
      low-income countries, the lack of functioning markets serves as a barrier to the
      transfer of necessary health technologies, and why governments must act as
      stewards in promoting technologies there.

PMID- 19597198
TI  - Dying to give birth: fighting maternal mortality in Peru.

PMID- 19597199
TI  - The rural hospital in Ecuador.
AB  - Over a period of twelve years, the author's vision of improving the health of
      rural Ecuadorians has evolved from an initial emphasis on primary health care to
      secondary care. The local community convinced him of the critical need for an
      efficiently managed, high-quality, and affordable rural secondary care hospital.
      Exploring a variety of funding options, the hospital ultimately achieved
      financial sustainability, principally through Ecuadorian public sources. Now, in
      partnership with the Ministry of Public Health (MOH), the rural hospital model
      that evolved in Pedro Vicente Maldonado is being adapted as a pilot project in an
      existing MOH rural hospital.

PMID- 19597200
TI  - Innovations in health services delivery from transition economies in Eastern
      Europe and Central Asia.
AB  - During the past fifteen years, the countries of the former Eastern Bloc
      transformed their centrally planned, supply-driven health care systems.
      Modernization of service delivery required innovations in financing and insurance
      and the restructuring of primary care and hospital networks. This review of
      experiences from Central and Southeast Europe, the Baltic States, Central Asia,
      and the Caucasus spot lights innovative health reforms in low- and middle-income
      countries, including contributions to improved service delivery, access to care,
      evidence-based medicine, and overall improvement in health system performance.

PMID- 19597201
TI  - An unhealthy public-private tension: pharmacy ownership, prescribing, and
      spending in the Philippines.
AB  - Physicians' links with pharmacies may create perverse financial incentives to
      overprescribe, prescribe products with higher profit margins, and direct patients
      to their pharmacy. Interviews with pharmacy customers in the Philippines show
      that those who use pharmacies linked to public-sector physicians had 5.4 greater
      odds of having a prescription from such physicians and spent 49.3 percent more
      than customers using other pharmacies. For customers purchasing brand-name
      medicines, switching to generics would reduce drug spending by 58 percent.
      Controlling out-of-pocket spending on drugs requires policies to control
      financial links between doctors and pharmacies, as well as tighter regulation of
      nongeneric prescribing.

PMID- 19597203
TI  - Does funding from donors displace government spending for health in developing
      countries?
AB  - The notable increases in funding from various donors for health over the past
      several years have made examining the effectiveness of aid all the more
      important. We examine the extent to which donor funding for health substitutes
      for--rather than complements--health financing by recipient governments. We find
      evidence of a strong substitution effect. The proportionate decrease in
      government spending associated with an increase in donor funding is largest in
      low-income countries. The results suggest that aid needs to be structured in a
      way that better aligns donors' and recipient governments' incentives, using
      innovative approaches such as performance-based aid financing.

PMID- 19597204
TI  - Borrowing and selling to pay for health care in low- and middle-income countries.
AB  - Many families around the world make sizable out-of-pocket payments for health
      care. We calculated the frequency of borrowing money or selling assets to buy
      health services in forty low- and middle-income countries and estimated how
      various factors are associated with these coping strategies. The data represented
      a combined population of 3.66 billion, or 58 percent of the world's population.
      On average, 25.9 percent of households borrowed money or sold items to pay for
      health care. The risk was higher among the poorest households and in countries
      with less health insurance. Health systems in developing countries are failing to
      protect families from the financial risks of seeking health care.

PMID- 19597205
TI  - Public views of health system issues in four Asian countries.
AB  - To elicit the public's views on health system issues, we conducted an opinion
      poll survey in Bangladesh, Mongolia, Nepal, and Sri Lanka. We focused on health
      inequalities. The results show high levels of dissatisfaction with government
      health services in all four of the countries. Access to government health
      services was an important concern. A sizable number of respondents reported that
      their governments did not consider their views at all in shaping health care
      services. The policy implications of the study findings are discussed.

PMID- 19597207
TI  - Polio eradication: strengthening the weakest links.
AB  - Polio eradication, like all eradication efforts, is a gamble. If it fails, much
      of the money spent will have been wasted. If it succeeds, the world will reap a
      dividend. Success or failure and the magnitude of the dividend depend on a long
      chain of "weakest links." In this paper I identify these links and explain how
      the chain can be strengthened. A crucial vulnerability is the current plan to
      halt vaccination using the live-attenuated oral polio vaccine in the post
      eradication era. This weakest link can be strengthened by efforts that lower the
      cost to poor countries of vaccinating with the inactivated poliovirus vaccine.

PMID- 19597208
TI  - Diplomacy and the polio immunization boycott in Northern Nigeria.
AB  - The boycott of polio vaccination in three Northern Nigerian states in 2003
      created a global health crisis that was political in origin. This paper traces
      the diplomatic actions that were taken by the Global Polio Eradication
      Initiative, the United Nations, and the U.S. government, to restart polio
      vaccination and resolve the crisis. The polio vaccination boycott in Northern
      Nigeria provides a useful case study of the practice of global health diplomacy.

PMID- 19597210
TI  - AIDS treatment in Brazil: impacts and challenges.
AB  - Brazil has one of the developing world's largest, and arguably most successful,
      AIDS treatment programs. In this paper we review the treatment program, including
      controversial policies that Brazil has used to promote widespread local and
      global access to AIDS treatment. We also examine the lessons learned from this
      program and highlight the challenges Brazil faces, including the rising costs of
      AIDS treatment and changes in donors' funding priorities. Finally, we explore the
      relevance of Brazil's treatment program for other countries and its broad
      implications for global AIDS and health policy.

PMID- 19597211
TI  - Public-private partnerships and public hospital performance in Sao Paulo, Brazil.
AB  - Public hospitals that are directly managed by government perform poorly in many
      developing countries. Approaches to improving them through internal managerial
      reforms have failed, and effective alternatives are much needed. Policymakers are
      considering reforms through public-private partnerships (PPPs)--a promising but
      so far unevaluated approach. We present results of a successful reform in Sao
      Paulo, Brazil. The PPP model gave facility managers latitude to manage human
      resources--a factor critical to success. Given the prevalence of direct
      management of public hospitals in developing countries, the Sao Paulo experience
      has implications for policymakers seeking to improve hospital performance.

PMID- 19597212
TI  - The health effects of decentralizing primary care in Brazil.
AB  - A renewed focus on primary health care could lead to improved health outcomes in
      developing countries. Moving more control to local authorities, or
      decentralization, is one approach to expanding primary care's reach. Proponents
      argue that it increases responsiveness to local needs and helps local resources
      reach those in need. Critics argue that it might increase fragmentation and
      disparities and provide opportunities for local economic and political gains that
      do not improve population health. We explore questions surrounding
      decentralization using the example of infant mortality in Brazil. Our study of
      two programs identified positive effects on health outcomes in the context of
      infant mortality.

PMID- 19597213
TI  - The political economy of U.S. primary care.
AB  - Compelling evidence suggests that the United States lags behind other developed
      nations in the health of its population and the performance of its health care
      system, partly as a result of a decades-long decline in primary care. This paper
      outlines the political, economic, policy, and institutional factors behind this
      decline. A large-scale, multifaceted effort--a new Charter for Primary Care--is
      required to overcome these forces. There are grounds for optimism for the success
      of this effort, which is essential to achieving health outcomes and health system
      performance comparable to those of other industrialized nations.

PMID- 19597214
TI  - High-deductible health insurance plans: efforts to sharpen a blunt instrument.
AB  - High deductible-based health insurance plans require consumers to pay for care
      until reaching the deductible amount. However, information is limited on how well
      consumers understand their benefits and how they respond to these costs. In
      telephone interviews, we found that consumers had limited knowledge about their
      deductibles yet frequently reported changing their care-seeking behavior because
      of the cost. Poor knowledge limited the effects of the deductible design, with
      some consumers avoiding care for services that were exempt from the deductible.
      Consumers need more information and decision support to understand their benefits
      and to differentiate when care is necessary, discretionary, or unnecessary.

PMID- 19597215
TI  - Outlier payments for cardiac surgery and hospital quality.
AB  - In 2002, several hospitals in the Tenet system were accused of overbilling
      Medicare for cardiac surgery. This led to increased scrutiny of so-called outlier
      payments, which are used to compensate hospitals when actual costs far exceed
      those anticipated under prospective payment. Since then, the overall proportion
      of coronary artery bypass graft (CABG) procedures associated with outlier
      payments has fallen from 13 percent in 2000-02 to 8 percent in 2003-06. Still,
      there is variation across U.S. hospitals, with some hospitals experiencing much
      higher rates. These findings imply that there is potential for quality
      improvement to reduce costs while improving morbidity and mortality.

PMID- 19597216
TI  - Narrative matters turns ten. Preface.

PMID- 19597217
TI  - On the southern front.

PMID- 19597218
TI  - In the midst of sickness.

PMID- 19597219
TI  - A touch of sense.

PMID- 19597220
TI  - Still closing the gap.

PMID- 19597221
TI  - Composite measures for predicting surgical mortality in the hospital.
AB  - Although payers increasingly report information on hospital volume and mortality
      from surgery, the value of these data is uncertain. Using national Medicare data
      for six surgical operations (covering the years 2003-2006), we created a
      composite measure based on these two quality indicators. We found that this
      simple measure was a strong predictor of future performance for all six
      operations. In this regard, it was more effective than the individual measures.
      Such measures would be useful for helping patients and payers identify low
      mortality hospitals for major surgery.

PMID- 19597222
TI  - Use of beta-blockers during aortic aneurysm repair: bridging the gap between
      evidence and effective practice.
AB  - The Leapfrog Group aims to improve patient safety and outcomes in hospitals
      through promoting the routine use of evidence-based medicine (EBM) practices such
      as the perioperative use of beta-blocker medications during elective abdominal
      aortic aneurysm (AAA) repair. The emergence of recent evidence, however, has
      sparked debate about the benefits of this practice. We found that implementation
      of the Leapfrog Group's beta-blocker standard in California hospitals has led to
      an estimated 50 percent decrease in mortality following open AAA repair over
      time. The efficacy and effectiveness of specific EBM practices must be
      continually reexamined, to ensure that objectives are being met.

PMID- 19597223
TI  - What do we really know about foundations' funding of mental health?
AB  - This paper examines mental health giving by foundations and points to a
      continuing downward trend in philanthropic giving to mental health, relative to
      overall and health giving. The authors reviewed data and interviewed staff from
      foundations that accounted for the majority of mental health funding in 2006.
      Using this quantitative and qualitative information, the authors identify
      important unanswered questions about foundation funding for mental health and
      suggest that the lack of precision in how mental health funding is defined and
      measured is symptomatic of the mental health field in general and may contribute
      to grantmakers' low level of attention to it.

PMID- 19597227
TI  - PhRMA's patient assistance programs.

PMID- 19597228
TI  - Medical team training in the VA system.

PMID- 19597229
TI  - Effects of mental health parity.

PMID- 19597230
TI  - Data on Thailand: a different perspective.

PMID- 19597232
TI  - Measuring the report card: the validity of P4P.

PMID- 19597234
TI  - Computerized order entry.

PMID- 19597236
TI  - Improved models of health care delivery.

PMID- 19597238
TI  - National health care policy: key to reform.

PMID- 19597239
TI  - [Pain, analgesia, and sex].
AB  - There is a large volume of data regarding sex differences in pain sensitivity and
      analgesia in both animals and in humans. It is difficult to analyze all the
      complex observations and find new aims for future studies. The main aspects of
      sex differences in sensitivity to and analgesia of experimental and clinical pain
      are described in this paper. The most important parameters which influence sex
      differences in pain perception are also presented.

PMID- 19597240
TI  - [Role of stellate cells in alcoholic liver fibrosis].
AB  - Many different diseases and toxins can cause liver damage, which is difficult to
      treat and often leads to the development of liver fibrosis or even cirrhosis. The
      key event in this process is the activation of hepatic stellate cells (HSCs).
      During such activation, HSCs undergo a dramatic transformation in morphology and
      behavior, changing from a neuronal-like to a fibroblast-like morphology. After
      activation, HSCs increase their proliferation rate and extracellular matrix
      (ECM)production. Overproduction of ECM, which contains mainly collagen type I, is
      a direct cause of liver disruption. HSCs also produce substances which inhibit
      protease activities, such as TIMPs,which enhance ECM deposition in the liver. On
      the molecular level, HSCs are activated by cytokines,growth factors, and
      oxidative stress, which are abundant in afflicted liver. These factors induce
      intracellular signals transmitted by many kinases, the most important of which
      are JNK,ERK1/2, p38, TAK-1, PKC, FAK, and P3IK. Signals transmitted via these
      pathways change the activities of transcription factors such as Smad, AP-1, and
      NF-kB. This in turn causes changes in gene transcription and ultimately alters
      the whole cell's behavior and morphology. The cell begins the production collagen
      type I, TIMP-1, and alphaSMA. Activated HSCs can sustain their own activation by
      producing growth factors such as PDGF and TGF-beta. Despite the vast knowledge
      about the mechanisms causing liver fibrosis and cirrhosis, there is still no
      effective cure. Further studies are therefore needed to solve this problem.

PMID- 19597241
TI  - [Seladin-1/DHCR24: a key protein of cell homeostasis and cholesterol
      biosynthesis].
AB  - Seladin-1 is a multifunctional protein encoded by DHCR24 gene and due to its
      enzymatic, antioxidant,and anti-apoptotic activities, it is considered as
      neuroprotective agent. Seladin-1 was identified as a gene down-regulated in brain
      regions selectively degenerated in Alzheimer's disease. Mutations of DHCR24 gene
      result in inhibition of the enzymatic activity of seladin-1, causing an
      accumulation of desmosterol and leading to a lethal disorder called
      desmosterolosis. Asan enzyme of cholesterol biosynthesis, seladin-1 enhances the
      formation of lipid rafts and caveoles.These membrane structures are involved in
      the maintenance of signaling pathways and metabolic processes, such as the
      degradation of amyloid precursor protein, which is especially significant in the
      pathophysiology of Alzheimer's disease. Independently of its enzymatic activity
      in cholesterol biosynthesis, seladin-1 acts as a caspase-3 inhibitor, a mediator
      of response to oxidative and oncogenic stress, and a reactive oxygen species
      scavenger. However, the effects of these activities seem to be indirectly
      modulated by membrane cholesterol level, which in turn gives priority to seladin
      1's enzymatic function in cholesterol biosynthesis, among its other functions.
      Seladin-1 is ubiquitously expressed, with the highest expression level in the
      brain and adrenal glands. Differences in seladin-1 expression profile were
      reported in transformed cells originating from many tissue types. Although the
      mechanisms of the regulation of seladin-1 activity demand further elucidation, it
      has already been shown that DHCR24 gene was activated byLXRa/RXRa in skin, by ERa
      in neurons, and by AR in prostate. Apart from estrogens and androgens,thyroid
      hormones, and IGF-1 also take part in the stimulation of seladin-1 expression.

PMID- 19597242
TI  - Field emission characteristics of point emitters fabricated by a multiwalled
      carbon nanotube yarn.
AB  - We fabricated point emitters using a multiwalled carbon nanotube (MWCNT) yarn
      which was treated by ethylene glycol. The point emitter showed a very high
      emission current of 3.01 mA (current density of 1.1 x 10(8) A cm(-2)) and good
      emission stability of over 20 h. We attributed the excellent field emission
      properties to a large field enhancement factor caused by the large aspect ratio
      of the sharp tip of the point emitter and the tight bonding of neighboring MWCNTs
      due to the ethylene glycol treatment. We investigated the field enhancement
      factor according to the gap between the anode and the emitter tip at a
      macroscopic gap regime. The measured field enhancement factor of the MWCNT point
      emitter was in good agreement with theoretical models.

PMID- 19597243
TI  - Multi-silicon ridge nanofabrication by repeated edge lithography.
AB  - We present a multi-Si nanoridge fabrication scheme and its application in
      nanoimprint lithography (NIL). Triple Si nanoridges approximately 120 nm high and
      40 nm wide separated by 40 nm spacing are fabricated and successfully applied as
      a stamp in nanoimprint lithography. The fabrication scheme, using a full-wet
      etching procedure in combination with repeated edge lithography, consists of hot
      H(3)PO(4) acid SiN(x) retraction etching, 20% KOH Si etching, 50% HF SiN(x)
      retraction etching and LOCal Oxidation of Silicon (LOCOS). Si nanoridges with
      smooth vertical sidewalls are fabricated by using Si 110 substrates and KOH
      etching. The presented technology utilizes a conventional photolithography
      technique, and the fabrication of multi-Si nanoridges on a full wafer scale has
      been demonstrated.

PMID- 19597244
TI  - In vitro photothermal destruction of neuroblastoma cells using carbon nanotubes
      conjugated with GD2 monoclonal antibody.
AB  - Despite aggressive multimodality therapy, most neuroblastoma-bearing patients
      relapse and survival rate remains poor. Exploration of alternative therapeutic
      modalities is needed. Carbon nanotubes (CNTs), revealing optical absorbance in
      the near-infrared region, warrant their merits in photothermal therapy. In order
      to specifically target disialoganglioside (GD2) overexpressed on the surface of
      neuroblastoma stNB-V1 cells, GD2 monoclonal antibody (anti-GD2) was conjugated to
      acidified CNTs. To examine the fate of anti-GD2 bound CNTs after incubation with
      stNB-V1 cells, rhodamine B was labeled on carboxylated CNTs functionalized with
      and without anti-GD2. Our results illustrated that anti-GD2-linked CNTs were
      extensively internalized by neuroblastoma cells via GD2-mediated endocytosis. In
      addition, we showed that anti-GD2 bound CNTs were not ingested by PC12 cells
      without GD2 expression. After anti-GD2 conjugated CNTs were incubated with
      neuroblastoma cells for 6 h and endocytosed by the cells, CNT-laden neuroblastoma
      cells were further irradiated with an 808 nm near-infrared (NIR) laser with
      intensity ramping from 0.6 to 6 W cm(-2) for 10 min which was then maintained at
      6 W cm(-2) for an additional 5 min. Post-NIR laser exposure, and after being
      examined by calcein-AM dye, stNB-V1 cells were all found to undergo necrosis,
      while non-GD2 expressing PC12 cells all remained viable. Based on the in vitro
      study, CNTs bound with anti-GD2 have the potential to be utilized as a
      therapeutic thermal coupling agent that generates heat sufficient to selectively
      kill neuroblastoma cells under NIR laser light exposure.

PMID- 19597245
TI  - Brilliant molecular nanocrystals emerging from sol-gel thin films: towards a new
      generation of fluorescent biochips.
AB  - To develop highly sensitive biosensors, we made directly available to biological
      aqueous solutions organic nanocrystals previously grown in the pores of sol-gel
      films. Through the controlled dissolution of the sol-gel surface, we obtained
      emerging nanocrystals that remained strongly anchored to the sol-gel coating for
      good mechanical stability of the final sensing device. We demonstrated that in
      the presence of a solution of DNA functionalized with a molecular probe, the
      nanocrystal fluorescence is strongly quenched by Forster resonance energy
      transfer thus opening the way towards very sensitive fluorescent biosensors
      through biomolecules grafted onto fluorescent nanocrystals. Finally, this
      controlled dissolution, involving weak concentrated NaOH solution, is a generic
      process that can be used for the thinning of any kind of sol-gel layer.

PMID- 19597246
TI  - Minimal cross-sensitivity to humidity during ethanol detection by SnO2-TiO2 solid
      solutions.
AB  - A nanocomposite material is presented that optimally combines the excellent gas
      sensitivity of SnO2 and the selectivity of TiO2. Nanostructured, rutile titanium
      tin oxide solid solutions up to 81.5% Ti, as determined by x-ray diffraction, are
      made by scalable spray combustion (flame spray pyrolysis) of organometallic
      precursor solutions, directly deposited and in situ annealed onto sensing
      electrodes in one step. Above that content, segregation of anatase TiO2 takes
      place. It was discovered that at low titanium contents (less than 5 Ti%), these
      materials exhibit higher sensitivity to ethanol vapor than pure SnO2 and, in
      particular, limited cross-sensitivity to relative humidity, a long standing
      challenge for metal oxide gas sensors. These solid solutions are aggregated
      nanoparticles with an enhanced presence of Ti on their surface as indicated by
      Raman and IR-spectroscopy. The presence of such low Ti-content in the SnO2
      lattice drastically reduces the band gap of these solid solutions, as determined
      by UV-vis absorption, almost to that of pure TiO2. Furthermore, titania reduces
      the number of rooted and terminal OH species (that are correlated to the cross
      sensitivity of tin oxide to water) on the particle surface as determined by IR
      spectroscopy. The present material represents a new class of sensors where
      detection of gases and organic vapors can be accomplished without pre-treatment
      of the gas mixture, avoiding other semiconducting components that require more
      heating power and that add bulkiness to a sensing device. This is attractive in
      developing miniaturized sensors especially for microelectronics and medical
      diagnostics.

PMID- 19597247
TI  - The construction of Si 2 Sb 2 Te 5 electrical probe storage based on UV
      nanoimprint lithography.
AB  - The Si(2)Sb(2)Te(5) (SST) storage array with a density of 2.4 Gbit inch(-2) was
      fabricated by UV nanoimprint lithography (UV-NIL) and filling semiconductor
      technology. The area of the SST storage cell contacted with electrodes was 0.031
      microm(2). Structural transformation of SST during heating was in situ studied by
      time-resolved x-ray diffraction (XRD). An electrical probe storage system was
      constructed by SST combining with a conductive atomic force microscope (C-AFM)
      with a nanoprobe. Switching of the SST electrical probe storage cell from the
      high resistance state to the low resistance state had been achieved, and the rate
      of these two resistance states was 37.71. The current increased apparently when
      the applied voltage exceeded 1.79 V.

PMID- 19597248
TI  - A simple and effective approach towards biomimetic replication of photonic
      structures from butterfly wings.
AB  - A general sonochemical process is reported for the replication of photonic
      structures from Morpho butterfly wings in several hours. By selecting appropriate
      precursors, we can achieve exact replications of photonic structures in a variety
      of transparent metal oxides, such as titania, tin oxide and silica. The exact
      replications at the micro- and nanoscales were characterized by a combination of
      FE-SEM, TEM, EDX and Raman measurements. The optical properties of the replicas
      were investigated by using reflectance spectroscopy, and it was found that the
      interesting chromaticity of the reflected light could be adjusted simply by
      tuning the replica materials. An ultrasensitive SnO(2)-based chemical sensor was
      prepared from the SnO(2) replica. The sensor has a sensitivity of 35.3-50 ppm
      ethanol at 300 degrees C, accompanied by a rapid response and recovery (around 8
      15 s), owing to its large surface area and photonic structure. Thus, this process
      could be developed to produce photonic structural ceramics which could be used in
      many passive and active infrared devices, especially high performance optical
      components and sensors.

PMID- 19597249
TI  - Localized surface plasmon resonance detection of layered biointeractions on
      metallic subwavelength nanogratings.
AB  - Enhanced detection of multiple targets such as self-assembled monolayer (SAM)
      formation, DNA hybridization, and ethanol ambient changes was explored using
      localized surface plasmon resonance (LSPR) excited by metallic surface
      nanogratings. The sensitivity enhancement depends on the target as well as the
      nanostructure with a maximum at 242% over a conventional structure when detecting
      an 11-mercaptoundecanoic acid SAM with an LSPR structure of 200 nm period. The
      measured enhancement shows smaller target-dependent variance when detecting
      various layered biointeractions, while structure-dependent variance was much
      larger. The result suggests the feasibility of the efficient detection of
      multiple biointeractions at enhanced sensitivity and extends the applicability of
      a nanostructured LSPR biosensor for diverse biomolecular events.

PMID- 19597250
TI  - Patterned carbon nanotube growth using an electron beam sensitive direct writable
      catalyst.
AB  - This paper reports the use of spin coatable Fe naphthenate (Fe(C(11)H(7)O(2))(2))
      as an electron beam sensitive direct writable catalyst suitable for growing high
      quality carbon nanotubes (CNTs). Vertically aligned, densely packed, equal in
      height, three- to four-walled and 5-7 nm inner diameter CNTs were grown on the
      nanoscale stripe patterns by water-assisted chemical vapor deposition. The
      correlation between electron beam dosage and the growth characteristics of CNTs
      is also discussed.

PMID- 19597252
TI  - Direct imaging of the visible emission bands from individual ZnO nanowires by
      near-field optical spectroscopy.
AB  - Room-temperature photoluminescence (PL) measurements have been performed on
      single-crystal ZnO nanowires grown on SiO2/Si and quartz substrates by the vapor
      transport method using Au as a catalyst. Two emission bands are apparent, one in
      the UV spectral region around 380 nm (3.26 eV) associated with exciton
      recombination processes and a much broader structure in the visible range from
      420 to 700 nm, which exhibits two distinct peak-like features around 520 and 590
      nm (2.38 and 2.10 eV). Spectrally resolved scanning near-field optical microscopy
      (SNOM) of single ZnO nanowires have been performed for a direct imaging of the PL
      emission with spatial resolution below 100 nm. SNOM results provide evidence that
      the yellow emission band observed at 590 nm is a unique property of the ZnO
      nanowires, being most likely related to radiative recombination processes
      associated with Au impurities introduced during the catalytic growth.

PMID- 19597251
TI  - Measurement of the thermal conductivity of a water-based single-wall carbon
      nanotube colloidal suspension with a modified 3- omega method.
AB  - A modified 3-omega method applied to a suspended platinum microwire was employed
      to measure the thermal conductivity and convective heat transfer coefficient of a
      water-based single-walled carbon nanotube (CNT) solution (metallic single-wall
      nanotubes with 1.33 nm diameter and 1.14 wt% concentration), and an expression
      for calculating the convective heat transfer coefficient in such a free
      convective fluid was introduced. The measurement technique was validated for
      three model systems including vacuum, air and deionized water. It is found that
      there is excellent agreement between these three model systems with theoretical
      predictions. In addition, the frequency dependence on the third harmonic response
      measured in deionized water reveals the existence of a very low working frequency
      below 60 mHz. The thermal conductivity and convective heat transfer coefficient
      of the nanofluid (water-based single-wall CNT solution) were determined to be
      0.73 +/- 0.013 W m(-1) K(-1) and 14 900 +/- 260 W m(-2) K(-1), respectively,
      which correspond to an enhancement of 19.4% in thermal conductivity and 18.9% in
      convective heat transfer as compared to water.

PMID- 19597253
TI  - A simple route to enhance the interface between graphite oxide nanoplatelets and
      a semi-crystalline polymer for stress transfer.
AB  - This report shows that thermal treatment is a simple and effective approach to
      create a polymer crystalline layer on the surface of graphite oxide nanoplatelets
      (GONPs) in polycaprolactone (PCL) melts. It was found that the crystallization
      temperature of the PCL increased significantly by nearly 9 degrees C with the
      incorporation of 2 wt% GONPs. As the composite melts isothermally crystallized at
      the temperature that was 14 degrees C higher than the crystallization
      temperature, the polymer crystalline layer was optimized on the surface of the
      GONPs. At 2 wt% GONPs, the Young's modulus of the composite was nearly 1.5 times
      greater than for the pure PCL. In comparison with untreated composites, the
      improvement in the Young's modulus of treated composites nearly doubled. It
      confirmed that a non-covalent interface for stress transfer can be enhanced by
      the formation of the polymer crystalline layer bridging the GONPs and the polymer
      matrix.

PMID- 19597254
TI  - Hydrothermal synthesis of ultrafine barium hexaferrite nanoparticles and the
      preparation of their stable suspensions.
AB  - The hydrothermal treatment of an appropriate suspension of Ba and Fe hydroxides
      in the presence of a large excess of OH(-) results in the formation of Ba
      hexaferrite at temperatures as low as 150 degrees C. This low formation
      temperature enables the synthesis of uniform, ultrafine Ba hexaferrite
      nanoparticles. These nanoparticles have a disc-like shape, approximately 10 nm
      wide, but only approximately 3 nm thick. When the temperature of the hydrothermal
      treatment is increased, large platelet Ba hexaferrite crystals appear as a
      consequence of secondary re-crystallization (Ostwald ripening). In this work,
      this undesired process of secondary re-crystallization has been evaluated. We
      show that the secondary re-crystallization can be totally suppressed with the use
      of an oleic acid surfactant. The addition of oleic acid enabled the synthesis of
      uniform, ultrafine nanoparticles at temperatures up to 240 degrees C. The
      nanoparticles were hydrophobic and could be suspended in nonpolar liquids to form
      relatively concentrated ferrofluids. Such stable suspensions of hexaferrite
      nanoparticles will be technologically important, especially as precursors for the
      preparation of new nanostructured materials, for example nanocomposites or
      nanostructured ceramic films.

PMID- 19597255
TI  - Solution-processable phosphorescent to organic light-emitting diodes based on
      chromophoric amphiphile/silica nanocomposite.
AB  - We report the synthesis of a tris-cyclometalated iridium complex which emits sky
      blue light and its potential use in phosphorescent light-emitting devices. The
      hybrid meso-structured nanocomposites by sol-gel co-assembly with tetraethyl
      ortho-silicate and corresponding molecular interactions within mesopores were
      also demonstrated. Electroluminescent devices were fabricated using carbazole
      based monomers and iridium complex as the active layer, acting as a host/guest
      system through a co-assembled sol-gel process. Devices based on this
      nanocomposite showed improved luminescent efficiencies several times higher than
      that of similar chromophores elaborated in the literature. A triple-layer
      electroluminescence device with the configuration of ITO/PEDOT/
      Ir(F2OC11ppy)(3):CA-C11:PBD nanocomposite/TPBI/Ca/Al showed a maximum brightness
      of 1389 cd m(-2) at 12 V and a maximum efficiency of 3.29 cd A(-1).

PMID- 19597256
TI  - The influence of a compatibilizer on the thermal and dynamic mechanical
      properties of PEEK/carbon nanotube composites.
AB  - The effect of polyetherimide (PEI) as a compatibilizing agent on the morphology,
      thermal, electrical and dynamic mechanical properties of poly(ether ether ketone)
      (PEEK)/single-walled carbon nanotube (SWCNT) nanocomposites, has been
      investigated for different CNT loadings. After a pre-processing step based on
      ball milling and pre-mixing under mechanical treatment in ethanol, the samples
      were prepared by melt extrusion. A more homogeneous distribution of the CNTs
      throughout the matrix is found for composites containing PEI, as revealed by
      scanning electron microscopy. Thermogravimetric analysis demonstrates an increase
      in the matrix degradation temperatures under dry air and nitrogen atmospheres
      with the addition of SWCNTs; the level of thermal stability of these
      nanocomposites is maintained when PEI is incorporated. Both differential scanning
      calorimetry and synchrotron x-ray scattering studies indicate a slight decrease
      in the crystallization temperatures of the compatibilized samples, and suggest
      the existence of reorganization phenomena during the heating, which are favoured
      in the composites incorporating the compatibilizer, due to their smaller crystal
      size. Dynamic mechanical studies show an increase in the glass transition
      temperature of the nanocomposites upon the addition of PEI. Furthermore, the
      presence of PEI causes an enhancement in the storage modulus, and hence in the
      rigidity of these systems, attributed to an improved interfacial adhesion between
      the reinforcement and the matrix. The electrical and thermal conductivities of
      these composites decrease with the incorporation of PEI. Overall, the
      compatibilized samples exhibit improved properties and are promising for their
      use in industrial applications.

PMID- 19597257
TI  - Synthesis of anti-aggregation silver nanoparticles based on inositol
      hexakisphosphoric micelles for a stable surface enhanced Raman scattering
      substrate.
AB  - We report a novel method of synthesizing a kind of silver nanoparticles aided by
      the inositol hexakisphosphoric micelle as a soft template and stabilizer. By
      controlling the reaction time, UV-vis and TEM observations of the size growth of
      the nanoparticles are performed. Careful examinations of surface enhanced Raman
      scattering (SERS) spectra of 2-mercaptopyridine (2-Mpy) on the as-produced silver
      nanoparticles exhibit very stable and reproducible Raman signals within about 4
      months.

PMID- 19597258
TI  - The synthesis of biocompatible and SERS-active gold nanoparticles using chitosan.
AB  - In this study we present a clean, nontoxic, environmentally friendly synthesis
      procedure to generate a large variety of gold nanoparticles (GNPs) by using
      chitosan, a biocompatible, biodegradable, natural polymer, as reducing and
      stabilizing agent. The formation of gold-chitosan nanocomposites was
      characterized by UV-vis absorption spectroscopy, transmission electron microscopy
      (TEM), x-ray diffraction (XRD) and Raman spectroscopy. The results show that the
      reaction temperature plays a crucial role in controlling the size, shape and
      crystalline structure of GNPs. In addition, it is demonstrated that chitosan can
      perform as a scaffold for the assembly of GNPs, which were successfully applied
      as substrate for surface-enhanced Raman scattering (SERS). To test the SERS
      activity, a relevant biological molecule--tryptophan--was adopted as the analyte.

PMID- 19597259
TI  - Optical control of phase transformation in Fe-doped TiO2 nanoparticles.
AB  - A series of anatase phase Fe-doped TiO2 nanoparticles are prepared by a modified
      sol-gel method. Spontaneous Raman spectroscopy is utilized to characterize the
      crystal structures of these nanoparticles and investigate their structural
      transformation under the exposure of a 532 nm green laser. The anatase phase of
      TiO2 can be effectively converted into the rutile phase with the assistance of Fe
      doping. It is found that the critical laser intensity for phase transformation
      decreases with increasing the Fe content. We ascribe this tendency to the
      enhanced optical absorption and the photo-induced thermal heating effect, which
      can be associated with the defect structure within the bandgap of Fe- TiO2
      nanoparticles. Our study demonstrates an all-optical approach to pump and probe
      the phase transformation of metal-doped TiO2 nanoparticles.

PMID- 19597260
TI  - The structure, energetics and thermal evolution of SiGe nanotubes.
AB  - The structure, energetics and thermal behavior of all the SiGe nanotubes in
      armchair and zigzag structures (n = 4-10) and two atomic arrangement types are
      investigated using the ab initio method and classical molecular dynamics
      simulations. Gearlike and puckering configurations of SiGe nanotubes are
      obtained. The simulation results indicate that large-diameter nanotubes are more
      stable than small-diameter ones. Moreover, the type 1 (alternating atom
      arrangement type) zigzag nanotubes are always more energetically favorable than
      the type 2 (layered atom arrangement type) zigzag nanotubes. During the melting
      process, the melting-like structural transformations from the initial nanotube to
      the compact nanowire take place first, and then the compact nanowires are changed
      into agglomerate structures at higher temperature. It is also found that the
      melting-like temperatures of Ge-substituted silicon nanotubes decrease with
      increase of the Ge concentration.

PMID- 19597261
TI  - The three-dimensional morphology of nickel nanodots in amorphous silica and their
      role in high-temperature permselectivity for hydrogen separation.
AB  - We report the development of technologically important nickel (Ni) nanodots
      (nanoparticles) dispersed in amorphous silica (SiO2) for high-temperature
      permselectivity for hydrogen separation membranes, crucial in hydrocarbon
      reactions and H(2) production, and present the systematic reconstruction of the
      three-dimensional (3D) structures of the nanodots using electron nano-tomography.
      3D structures using cryogenic high-angle annular dark field scanning transmission
      electron microscopy (Cryo-HAADF-STEM), which is a more accurate method for
      nanoparticle morphology than conventional chemisorption, are correlated with
      experimental reversible hydrogen adsorption properties. The correlations provide
      the first direct evidence of very high activity on the nanoparticle surface and
      the nature of adsorption sites. The results have important implications in
      general for the use of electron nano-tomography in the design of supported
      metallic nanoparticles for hydrogen separation membranes.

PMID- 19597262
TI  - Dislocations in Si nanocrystals embedded in SiO2.
AB  - Si nanocrystals (Si nc) were formed by the implantation of Si(+) into a SiO2 film
      on (100) Si, followed by high-temperature annealing. High-resolution transmission
      electron microscopy has been used to investigate the dislocations in the Si nc
      produced by a high-dose (ion fluence of 3 x 10(17) cm(-2)) implantation. Three
      different kinds of dislocations, namely perfect, extended and mismatch
      dislocations, have been observed in some Si nc. The possible formation mechanism
      for these dislocations has been discussed. The dislocations in the Si nc are
      expected to have a great influence on the photoluminescence from Si nc embedded
      in SiO2.

PMID- 19597263
TI  - Tailoring the physical properties of thiol-capped PbS quantum dots by thermal
      annealing.
AB  - We show that the thermal annealing of thiol-capped PbS colloidal quantum dots
      provides a means of narrowing the nanoparticle size distribution, increasing the
      size of the quantum dots and facilitating their coalescence preferentially along
      the 100 crystallographic axes. We exploit these phenomena to tune the
      photoluminescence emission of an ensemble of dots and to narrow the optical
      linewidth to values that compare with those reported at room temperature for
      single PbS quantum dots. We probe the influence of annealing on the electronic
      properties of the quantum dots by temperature dependent studies of the
      photoluminescence and magneto-photoluminescence.

PMID- 19597264
TI  - Hierarchical plasticity from pair distance fluctuations.
AB  - Observations, experiments and simulations often generate large numbers of
      snapshots of configurations of complex many-body systems. It is important to find
      methods of extracting useful information from these ensembles of snapshots in
      order to document the motion as the system evolves in time. Some of the most
      interesting information is contained in the relative motion of individual
      constituents, rather than their absolute motion. We present a novel statistical
      method for identifying hierarchies of plastically connected objects in a system
      from a series of two or more snapshot configurations. These plastic clusters are
      distinctive in that although their members tend to remain loosely connected, the
      clusters may be deformed plastically. This method is demonstrated for a number of
      systems, including an exactly soluble freely jointed polymer chain model, a two
      dimensional simulation of two species of interacting bodies and a protein. These
      concepts are implemented as TIMME, the Tool for Identifying Mobility in
      Macromolecular Ensembles.

PMID- 19597265
TI  - Tug of war in motility assay experiments.
AB  - The dynamics of two groups of molecular motors pulling in opposite directions on
      a rigid filament is studied theoretically. To this end we first consider the
      behavior of one set of motors pulling in a single direction against an external
      force using a new mean-field approach. Based on these results we analyze a
      similar setup with two sets of motors pulling in opposite directions in a tug of
      war in the presence of an external force. In both cases we find that the
      interplay of fluid friction and protein friction leads to a complex phase diagram
      where the force-velocity relations can exhibit regions of bistability and
      spontaneous symmetry breaking. Finally, motivated by recent work, we turn to the
      case of motility assay experiments where motors bound to a surface push on a
      bundle of filaments. We find that, depending on the absence or the presence of
      bistability in the force-velocity curve at zero force, the bundle exhibits
      anomalous or biased diffusion on long-time and large-length scales.

PMID- 19597266
TI  - Dorsiflexor muscle-group thickness in children with cerebral palsy: relation to
      cross-sectional area.
AB  - If the thickness and cross-sectional area of the dorsiflexor muscle group are
      related in children with cerebral palsy, measurements of muscle thickness may be
      used to monitor changes in muscle size due to training or immobilisation in these
      patients. We assessed the validity and reliability of measurements of dorsiflexor
      muscle-thickness using the cross-sectional area of the muscle group as the
      criterion-related muscle-size variable. Muscle thickness was measured using
      ultrasound, and cross-sectional area using MRI in nine children with spastic
      cerebral palsy (eight with hemiplegia). Test-retest reliability of the muscle
      thickness measurements was assessed in six healthy subjects. All measurements
      were made on both legs at 35% lower leg length. In the children with cerebral
      palsy, dorsiflexor muscle-thickness and cross-sectional area were well correlated
      (r(2) = 0.778, P < 0.001), and the reliability of the muscle-thickness
      measurements was high in the healthy subjects (ICC(2.1) = 0.94, standard error of
      measurement = 0.04 cm). The dorsiflexor muscle-thickness was 22% less in the
      affected compared to the non-affected leg in children with hemiplegic cerebral
      palsy (P < 0.001). Accordingly, the dorsiflexor cross-sectional area was 32% less
      in the affected compared to the non-affected leg (P = 0.002). Measurements of
      dorsiflexor muscle-thickness can be reliably obtained, and they reflect
      dorsiflexor cross-sectional area in children with cerebral palsy.

PMID- 19597267
TI  - Effects of task-oriented training on mobility function in children with cerebral
      palsy.
AB  - BACKGROUND/PURPOSE: Improvement in mobility function has been the primary goal in
      the rehabilitation of children with cerebral palsy. Few studies have examined the
      effectiveness of task-oriented strength training for children with cerebral
      palsy. The purpose of this study was to examine the effects of task-oriented
      strength training on mobility function in children with cerebral palsy. STUDY
      DESIGN: A single-blind, randomized controlled trial with pre-training and post
      training evaluations. MATERIALS AND METHODS: Ten children with cerebral palsy
      (GMFCS levels I-III) were randomly assigned to an experimental group (N = 5) or
      control group (N = 5). Mobility function was assessed using the Gross Motor
      Function Measure (GMFM) and the Timed "Up and Go" (TUG) test. Participants in the
      control group received conventional physical therapy focused on improving walking
      and balance through facilitation and normalization of movement patterns.
      Participants in the experiment group received task-oriented strength training
      focused on strengthening the lower extremities and practicing functional tasks
      similar to those the child performs during daily activities. RESULTS: After the 5
      week training period there were significant improvements in the experimental
      group for dimension D (p = 0.009), and dimension E (p = 0.009) of the GMFM. The
      experimental group significantly reduced the time taken to complete the TUG (p =
      0.017). CONCLUSION/SIGNIFICANCE: This study supports the efficacy of task
      oriented strength training for improving mobility function in children with
      cerebral palsy. The findings demonstrate that the application of a task-oriented
      strength training program is linked to positive functional outcomes. The results
      suggest that children with cerebral palsy may benefit from a task-oriented
      strength training program. Further studies with a larger randomized sample and
      longer post-intervention follow-up are necessary to document the long-term
      effects of participation in task-oriented strength training programs in the
      cerebral palsy population.

PMID- 19597268
TI  - A review of the ipsilateral motor pathway as a recovery mechanism in patients
      with stroke.
AB  - The ipsilateral motor pathway is a normal motor control pathway and is accepted
      as one of the recovery mechanisms after stroke. Among the motor recovery
      mechanisms following stroke, the ipsilateral motor pathway from the unaffected
      motor cortex to the affected extremities has been the most actively researched.
      This mechanism is important clinically because it contributes to motor recovery
      in the early stages after the onset of stroke, and is related to poor motor
      outcome. In addition, the ipsilateral motor pathway can be manipulated by various
      rehabilitative interventions. We have reviewed the literature on the ipsilateral
      motor pathway in stroke patients in relation to the methods of evaluation,
      previous studies, the underlying pathophysiologic mechanism, clinical
      characteristics, and rehabilitative aspects.

PMID- 19597269
TI  - Predictors of functional outcome in first-ever ischemic stroke: a special
      interest to ischemic subtypes, comorbidity and age.
AB  - OBJECTIVES: Most cardiovascular abnormalities are associated not only with
      increased risk of certain ischemic stroke subtypes but also with markedly greater
      disability in stroke patients. We aimed to investigate the associations between
      age, comorbidity, cardiovascular problems, site and size of ischemic lesions and
      functional outcome in inpatient first-ever ischemic stroke patients. SUBJECTS: A
      total of 129 first-ever ischemic stroke admissions to a university affiliated
      rehabilitation centre were involved. METHODS: Demographic data, brain
      computerized tomography or magnetic resonance imaging reports of the patients
      were recorded. Cardiovascular parameters consisted of electrocardiographic,
      echocardiographic and carotid Doppler ultrasonographic findings. Location and
      size of ischemic lesions was determined by using the Oxfordshire Community Stroke
      Project classification. Charlson Comorbidity index adjusted for ischemic stroke
      was used to assess associated health problems. Functional recovery was defined as
      the improvements made on Functional Independence Measure. RESULTS: Our data
      indicated that the presence of chronic atrial fibrillation and carotid stenosis
      had significant associations with total anterior circulation infarcts.
      Multivariate analyses revealed that age, Charlson Comorbidity index adjusted for
      ischemic stroke, total anterior circulation infarcts, Functional Independence
      Measure on admission were associated with rehabilitation outcomes. CONCLUSIONS:
      Advanced age, high comorbidity, large anterior circulation infarcts and poor
      functional level on admission were independent indicators of unfavorable
      functional outcome. Hemodynamic comorbidities had significant impact on
      localization and extend of ischemic lesions.

PMID- 19597270
TI  - Effect of a 4-week period of unloaded leg cycling exercise on spasticity in
      multiple sclerosis.
AB  - We conducted a small pilot study that examined the effect of a 4-week period of
      unloaded leg cycling on spasticity in individuals with multiple sclerosis (MS).
      The sample included 22 individuals with MS who were assigned using a quasi
      experimental method into either exercise (n = 12) or control (n = 10) conditions.
      The exercise condition consisted of unloaded leg cycling for 30 minutes per
      session, 3 times per week, across a 4-week period. The control condition served
      as a control for passage of time and instrumentation effects. The H-reflex,
      modified Ashworth scale (MAS), and Multiple Sclerosis Spasticity Scale (MSSS-88)
      were collected before, 1-day after, and 1 and 4 weeks after the 4-week period.
      The 4-week period of unloaded leg cycling exercise was not associated with
      reductions in the H-reflex or MAS, whereas the exercise condition was associated
      with a reduction in MSSS-88 scores. This pattern of results suggests that
      chronic, unloaded leg cycling exercise is associated with improvements in
      spasticity from the participant's perspective, but neither improves nor worsens
      spasticity from electrophysiological and clinical perspectives.

PMID- 19597271
TI  - A pilot study of a comparison between a patient scored numeric rating scale and
      clinician scored measures of spasticity in multiple sclerosis.
AB  - OBJECTIVE: To assess the validity and reliability of a Numeric Rating Scale (NRS)
      for the measurement of spasticity in multiple sclerosis. DESIGN: Longitudinal
      study with multiple comparators over two clinic visits. SETTING: Rehabilitation
      Centre in the North East of England, UK. SUBJECTS: A total of thirty-five
      patients, with a diagnosis of multiple sclerosis (MS) that were attending a
      rehabilitation clinic. RESULTS: The test/re-test reliability of the NRS showed
      there was a high correlation between the two visits (r = 0.672). Construct
      validity was assessed by examining the relationship between the mean spasticity
      NRS and each of the other spasticity assessment tools. There was a statistically
      significant correlation between subject's mean NRS diary scores and the Modified
      Ashworth Scale scores at both visits (Visit 1, r = 0.459, p = 0.0056; Visit 2, r
      = 0.446, p = 0.0106). There was a moderate, statistically significant correlation
      between the mean NRS diary scores and the Tardieu Scale (Visit 1, r = 0.429, p =
      0.0113; Visit 2, r = 0.407, p = 0.0209). CONCLUSIONS: The spasticity NRS has been
      shown to be a valid and reliable tool in the assessment of spasticity with a
      moderate to high level of correlation with other clinician rated instruments used
      to assess spasticity.

PMID- 19597272
TI  - Evaluation of patients with spinal operation according to functional mobility.
AB  - OBJECTIVE: The aim of our study is to determine the effect of age, BMI (Body Mass
      Index: kg/m(2)), gender, level of lumbar disc operation and standardized
      physiotherapy of the patients during hospitalization on the Physiotherapy
      Functional Mobility Profile (PFMP). DESIGN: A retrospective study. PATIENTS:
      Eighty three patients who had undergone surgery with lumbar disc hernia were
      included in the study. Data were separately interpreted considering such
      parameters as age, BMI, gender, and level of operation which we believe might
      have affected the associated consequences. METHODS: PFMP was used in the
      assessment of the patients. Evaluations were made on the days when they were
      referred and discharged. RESULTS AND CONCLUSION: Increases were observed in
      totals and subheadings of PFMP scores during the early period of the inpatients
      exposed to lumbar disc operations to whom we applied standardized physiotherapy
      programs, with increases in subheadings involving ambulation being found
      significant. It follows from the conclusions of grouping our patients that
      functionality was positively influenced by 4th decade muscularity and by one
      level operation in the early period.

PMID- 19597273
TI  - Review of motor recovery in patients with traumatic brain injury.
AB  - Detailed information about motor recovery is essential for brain rehabilitation
      because it enables us to establish scientific rehabilitative strategies and
      predict motor outcome. For this review, we summarized the literature on motor
      recovery of patients with traumatic brain injury (TBI) in relation to the
      following: epidemiology of motor weakness, mechanisms of injury that cause motor
      weakness, course of motor recovery, and mechanisms underlying motor recovery. The
      motor weakness in patients with TBI is characterized by a low incidence,
      decreased severity, long recovery time, and good motor outcome when comparing
      with cognitive or behavior problems following TBI or the motor weakness affecting
      stroke patients. However, there are few studies describing the course of motor
      recovery and the underlying mechanisms of motor recovery. Knowledge in the course
      of recovery and the mechanisms of recovery can alert clinicians to obtain the
      salient information about the critical period for rehabilitation and the
      rehabilitative strategies respectively. Therefore, we suggest that further
      research should focus on these topics.

PMID- 19597274
TI  - Treating underlying attention deficits as a means for improving conversational
      discourse in individuals with closed head injury: a preliminary study.
AB  - BACKGROUND: It is documented that individuals with closed head injury (CHI)
      demonstrate difficulty with narrative and conversational discourse. Effective
      conversational discourse requires a complex interaction of linguistic, cognitive,
      and social abilities [6]. Reduced attention and concentration are among the most
      common cognitive sequela following CHI [39]. AIMS: The present study investigated
      whether treatment of attention would facilitate conversational discourse for
      individuals with CHI. Two treatment protocols were investigated, the first social
      skills-based, and the second attention-based. It was hypothesized that attention
      training would improve not only attentional skills but also conversation, however
      social skills training, would only facilitate conversational skills. METHODS AND
      PROCEDURES: A single subject multiple treatments comparison design was employed
      with two individuals who were post-onset of CHI. Treatment effects on
      conversational performance were calculated using the f statistic [18] for
      measures of response appropriateness during conversations. OUTCOMES AND RESULTS:
      Effect sizes suggested that both treatments were active; however, the
      participants' performances were variable reducing the magnitude of change
      observed. Results indicated minimal change from baselines, only partially
      supporting the research hypotheses. CONCLUSIONS: Although the two treatment
      regimens had some effect on the participants' conversational performances it was
      not to the extent anticipated. The issues of candidacy for such treatments as
      well as the importance of incorporating natural contingencies into interventions
      for conversation training are discussed.

PMID- 19597275
TI  - Do clients with acquired brain injury use the splints prescribed by occupational
      therapists? A descriptive study.
AB  - Clients with acquired brain injury often demonstrate hypertonicity and decreased
      function in their upper limbs, requiring appropriate intervention. Splinting is
      one of the intervention methods that is widely used to address these issues.
      Literature shows that some clients are not using splints following fabrication.
      However, there is a paucity of research about the factors that influence clients
      to use or not use splints. This study aims to investigate these influential
      factors for clients with upper limb hypertonicity. Two survey tools including
      therapist and client questionnaires were developed and completed by both
      therapists and clients. Six therapists and 14 clients participated in this study
      and completed the relevant questionnaires. The results illustrate that most
      clients (13 out of 14) were continuing to use their splints four weeks following
      discharge from hospital. The main goals of choosing splints for both therapists
      and clients were prevention of contracture and deformity. The most indicated
      client reasons for adhering to the splint wearing program were therapist-related
      factors including clients' trust and reliance on their therapists. Further
      reasons for clients implementing the recommended splint-wearing program and
      clinical implications are discussed.

PMID- 19597276
TI  - Analysis of intensive outpatient neuro-rehabilitation outcomes using FIM+FAM(UK).
AB  - OBJECTIVE: To analyse the functional outcomes of adults following acquired brain
      injury attending an intensive outpatient neuro-rehabilitation programme relative
      to a comprehensive TBI day programme service in the United States. METHOD: 
      DESIGN: Retrospective audit of all admissions over a two-year period (2001-2003)
      to an outpatient neuro-rehabilitation service utilising an interdisciplinary team
      model. SETTING: Outpatient neuro-rehabilitation service. PARTICIPANTS: 89
      patients in receipt of 2+ therapies attending for intensive day neuro
      rehabilitation programme. MAIN OUTCOME MEASURES: Routine FIM+FAM(UK) scores were
      compiled on admission and discharge. The FIM+FAM(UK) is a widely employed outcome
      measure of activity and participation comprising 30 items across a range of
      domains including self care, domestic skills, mobility, communication, cognitive
      and social abilities. The scale is divided into two broad domains of functioning
      (motor and cognitive). DATA ANALYSIS: Descriptive analysis of demographic,
      patient diagnosis, referral patterns and time since injury to attendance was
      undertaken. Analysis of FIM+FAM(UK) admission and discharge scores was performed.
      RESULTS: Complete admission and discharge scores were available for 65 patients.
      Significant mean improvements in motor (12.0 point change), cognitive (7.3 point
      change) and composite FIM+FAM(UK) (19.3 point change) scores were observed
      indicating reduced functional dependence following an intensive period of
      outpatient neuro-rehabilitation. CONCLUSION: The FIM+FAM(UK) measure demonstrated
      sensitivity to change across functional domains relevant to goal directed
      intensive outpatient interdisciplinary neuro-rehabilitation.

PMID- 19597277
TI  - Improvement of hand sensibility after selective temporary anaesthesia in
      combination with sensory re-education.
AB  - PURPOSE: The results of nerve repair in adults are often poor. The study aim was
      to investigate the effect of repeated sessions of cutaneous forearm anaesthesia
      of the injured limb, in combination with sensory re-education on the recovery of
      the tactile discrimination and perception of touch/pressure in the injured hand
      after median or ulnar nerve repair. METHODS: A prospective, randomized, double
      blind clinical trial was designed. During a 2-week period, a topical anaesthetic
      cream (Lidocaine-PTC, n = 6) or placebo (n = 7) was applied repeatedly (twice a
      week) with occlusive bandage for 1 hour on the flexor aspect of the forearm of
      the same side of the nerve injury and combined with sensory re-education.
      Assessments of sensory function were performed prior to the experiment and after
      the fourth application of Lidocaine-PTC/placebo. The patients were evaluated
      again 4 weeks after the last Lidocaine-PTC/placebo session. RESULTS: Touch
      perception measured with Semmes-Weinstein Monofilaments (SWM), improved
      significantly in the Lidocaine-PTC group (p = 0.005). In placebo group, no
      significant changes were seen. Two{-}point discrimination improved significantly
      only in the Lidocaine-PTC group (p = 0.005). CONCLUSION: This finding suggests
      that forearm deafferentation of injured limb in combination with sensory re
      education can enhance sensory recovery after nerve repair.

PMID- 19597280
TI  - Job strain and older workers: Can a reduction in job strain help to eliminate the
      social security drain?
AB  - Job strain is the psychological and physiological response to a lack of control
      or support in the work environment. It appears to be an important risk factor for
      continued employment throughout the lifespan. Reducing job strain earlier in a
      workers life has the potential to have substantial beneficial health effects
      throughout a workers life. Early screening for job strain should be implemented
      in known high risk or high strain jobs. This is particularly important since
      there a fewer younger workers entering the labor force and there will be a
      growing need for older workers to remain in the workforce. Furthermore, healthier
      workers will require less medical care and are likely to work longer if they are
      willing and able. Healthier older workers who are willing and able to work longer
      will defer receipt of retirement benefits while continuing to pay into the Social
      Security System. Further investigation of older individuals (1) willingness and
      motivation to work past the normal retirement age, (2) career and employment
      security, skills development, and reconciliation of working and non-working life,
      and (3) job strain and effects of reducing job strain is needed. The current job
      strain literature has been expanded to the Social Security System arena and
      suggests that reducing job strain has the potential to help eliminate the Social
      Security drain by increasing older worker labor force retention.

PMID- 19597281
TI  - How do employees and managers perceive depression: a worksite case study.
AB  - BACKGROUND: The impact of depression in the workplace is significant. If managers
      and employees understood depression better they could assist those with
      depression to achieve optimal work performance. METHOD: The case study was a
      medium-sized, privately owned forest products company located in western Canada.
      Individual interviews were used to explore the views of employees and managers
      about depression and its impact on work performance. FINDINGS: Suggest that how
      one perceives workplace support for depression is influenced by the interaction
      of the following factors: a) knowledge and understanding of depression, b) roles
      and responsibilities within the work environment, and c) perceptions of work role
      boundaries. CONCLUSION: Better links are needed between employees and managers to
      enhance workplace collaborations and achieve optimal work performance. The
      implementation of mental health support programs and the vocational role of
      occupational therapy in addressing the impact of depression in the workplace are
      discussed.

PMID- 19597282
TI  - Identifying modifiable causes of fall-related injury: an analysis of U.S. Army
      safety data.
AB  - Details on fall-related circumstances, a leading cause of occupational injury,
      are scarce. This study aimed to identify modifiable causes of falls using data
      from safety reports. Coded and narrative data on injured persons, event
      locations, and circumstances associated with falls sustained by U.S. Army
      personnel were obtained from safety reports dated September 1994-September 2002.
      Descriptive statistics are presented for injury outcomes and risk factors, with a
      focus on falls from elevation. On average, 59 fall-related injuries/100,000
      person-years were reported. Higher rates occurred among whites, single persons,
      and 20-24 year-olds. Falls from elevation resulted in more severe outcomes,
      longer hospitalizations, and more lost work time compared to falls from the same
      level. Most falls from elevation occurred in training (32%) and housing (18%)
      areas. Leading causes included routine activities (e.g., walking,
      entering/exiting vehicles) (35%), physical training (12%), and sports (12%).
      Interventions to prevent falls from elevation in this population should focus on
      reducing risks from routine activities, specifically in training and housing
      areas. Safety reports provided details necessary for prioritizing and planning
      fall prevention efforts that are not available from other sources.

PMID- 19597283
TI  - Why has a woman with mental illness been fired? Discourses on fairness and
      diversity management.
AB  - Being fired can be perceived as a form of unfair treatment and as a personal and
      social defeat. It can generate feelings of anger, outrage and resentment that can
      elicit a desire for retribution. This qualitative study focuses on a case of
      failed integration of a person with a mental illness at the workplace. Texts were
      analysed from a rhetorical perspective, considering how the company leaders and
      the employee re-constructed and gave meaning to the events that lead to the
      firing, trying to justify them. Policies dealing with workplace diversity and the
      hiring of people with disabilities, power relations, fit between organizational
      goals and ideal models of behaviour in the company on one hand, and personal
      needs of the employee on the other, seem to be determinant in influencing the
      perception the parties have of interactional and procedural justice.

PMID- 19597284
TI  - The associations between perceived distributive, procedural, and interactional
      organizational justice, self-rated health and burnout.
AB  - AIM: The aim of the present study was to examine the cross-sectional and 2-year
      longitudinal associations between perceived organizational justice, self-rated
      health and burnout. METHODS: The study used questionnaire data from 428 Swedish
      employment officers and the data was analyzed with Structural Equation Modeling,
      SEM. Two different models were tested: a global organizational justice model
      (with and without correlated measurement errors) and a differentiated
      (distributive, procedural and interactional organizational justice) justice model
      (with and without correlated measurement errors). RESULTS: The global justice
      model with autocorrelations had the most satisfactory goodness-of-fit indices.
      Global justice showed statistically significant (p < 0.01) cross-sectional (0.80
      {mle 0.84) and longitudinal positive associations (0.76 mle 0.82) between
      organizational justice and self-rated health, and significant (p < 0.01) negative
      associations between organizational justice and burnout (cross-sectional: mle = 
      0.85, longitudinal -0.83 mle -0.84). CONCLUSION: The global justice construct
      showed better goodness-of-fit indices than the threefold justice construct but a
      differentiated organizational justice concept could give valuable information
      about health related risk factors: if they are structural (distributive justice),
      procedural (procedural justice) or inter-personal (interactional justice). The
      two approaches to study organizational justice should therefore be regarded as
      complementary rather than exclusive.

PMID- 19597285
TI  - Goal clarity as an instrument for improved organizational wellbeing in the Church
      of Sweden.
AB  - Lack of goal clarity is known to have negative effects on organizational as well
      as individual wellbeing. This study assesses effects of goal clarity on
      organizational wellbeing in the Church of Sweden. Data was based on
      questionnaires from a random sample of 501 parishes and 1002 individuals from the
      upper parish management. The response rate was 62%. The results showed
      significantly more positive experiences of effects of goal clarity on
      organizational wellbeing for those having former experience with of this type of
      work and among those representing larger parishes. Older employees reported a
      higher degree of engagement in the work while younger employees expressed a
      higher degree of influence. The results suggest that work with goal clarity has a
      positive impact on organizational wellbeing, which in turn is expected to have
      positive effects on employee wellbeing. Further research is required to examine
      the relationships between goal clarity work and organizational as well as
      individual wellbeing.

PMID- 19597286
TI  - Empowerment variables for rehabilitation clients on perceived beliefs concerning
      work quality of life domains.
AB  - This article describes and presents an initial analysis of variables generally
      associated with empowerment towards perceived beliefs concerning quality of life
      work domains for individuals with disabilities. The model examines the domains of
      importance, satisfaction, control and degree of interference of disability that
      an individual feels towards work. The internet based study used results from 70
      individuals with disabilities in varying aspects of work. The variables composing
      empowerment that correlated strongly with the work domains include: self
      advocacy, self-efficacy, perceived stigma, and family resiliency as measured
      through coping. Quality of Life concerning work was measured through the DSC-C a
      domain specific QOL instrument.

PMID- 19597287
TI  - Predictors of competitive employment among persons with physical and sensory
      disabilities: an evidence-based model.
AB  - Persons with physical and sensory disabilities continue to face difficulty
      securing and maintaining employment. Despite all of the efforts of individuals
      providing assistance to job seekers, family members, friends and colleagues, the
      employment deficit of people with disabilities has remained nearly static for
      years. This study examined factors salient to the attainment of competitive
      employment among people with physical and sensory disabilities served by the
      state-federal rehabilitation system. Employing a series of logistic regression
      analyses measured against national rehabilitation data, the results support the
      need for provision of job placement services to improve potential for competitive
      employment. Predictors of competitive employment, job placement service provision
      implications, the need for vocational evaluation and appropriate planning are
      discussed. An evidence-based service model designed to address the predictors of
      competitive employment among persons with physical and sensory disabilities is
      presented.

PMID- 19597288
TI  - A systematic review of preventive interventions regarding mental health issues in
      organizations.
AB  - The most recent review of the workplace prevention literature was published two
      decades ago. Since then, interest has been growing in the business and research
      communities in preventive workplace interventions. At the same time, there has
      been an increasing recognition of the complexity of developing workplace
      interventions. This study's purpose is to assess the literature from 2001 to 2006
      using Cottrell's conceptualization to: 1) conduct a systematic review of the most
      recent literature, 2) describe the preventive psychological interventions for
      workers, 3) summarize the significant work- and health-related outcomes
      associated with these interventions, and 4) identify where the significant gaps
      still exist. Twenty-four studies on primary and secondary interventions regarding
      mental health issues in organizations were included and analyzed in this
      systematic review. Eight studies were identified as primary interventions, 14
      were identified as secondary interventions, and 2 included both. There was a
      predominance of studies utilizing skills training. One-third of studies used a
      combination of individual, group and organization level interventions, most often
      supported by psychosocial intervention or participatory research. These
      components brought positive and significant results with regard to work and
      mental health outcomes to workers.

PMID- 19597289
TI  - Job characteristics and work organization factors associated with patient
      handling injury among nursing personnel.
AB  - The aim of this cross-sectional study was to explore the association of worker
      characteristics and work organization factors with prevalence of patient-handling
      injury among nursing personnel in an acute-care inpatient setting. Self
      administered questionnaires (n = 585) captured worker characteristics and patient
      handling injuries within the previous 6 months. Karasek's Job Content
      Questionnaire measured work organization factors, including job strain (high
      psychological demand, low decision latitude). We created a novel measure (job
      strain(PHYSICAL)) reflecting high physical demand and low decision latitude,
      providing a more direct physiologic link to our outcome. Log-binomial regression
      was used to calculate prevalence ratios (PR) and 95% confidence intervals (CI).
      Patient-handling injuries were prevalent (35%), and incident reports were filed
      infrequently for injuries receiving medical care. Prevalence of injury was higher
      among aides compared to nurses [adjusted PR 1.4, 95%CI (1.1-1.8)] as well as
      among those with high [adjusted PR 1.6, 95%CI (1.2-2.4)] or mid [adjusted PR 1.9,
      95%CI (1.4-2.7)] levels of job dissatisfaction. The novel definition of job
      strain (job strain(PHYSICAL): high physical demand, low decision latitude) was
      more strongly associated with patient-handling injury than the traditional
      definition of job strain (high psychological demand, low decision latitude).
      These findings add to a growing body of literature on the highly contextual
      nature of work organization factors.

PMID- 19597290
TI  - Cost of future care determinations: ethical and professional challenges.

PMID- 19597291
TI  - Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical
      carcinoma.
AB  - Due to the highly glycolytic metabolism of solid tumours, there is an increased
      acid production, however, cells are able to maintain physiological pH through
      plasma membrane efflux of the accumulating protons. Acid efflux through MCTs
      (monocarboxylate transporters) constitutes one of the most important mechanisms
      involved in tumour intracellular pH maintenance. Still, the molecular mechanisms
      underlying the regulation of these proteins are not fully understood. We aimed to
      evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT
      expression in cervical cancer lesions and the clinico-pathological significance
      of CD147 expression, alone and in combination with MCTs. The series included 83
      biopsy samples of precursor lesions and surgical specimens of 126 invasive
      carcinomas. Analysis of CD147 expression was performed by immunohistochemistry.
      CD147 expression was higher in squamous and adenocarcinoma tissues than in the
      non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more
      frequently expressed in CD147 positive cases. Additionally, co-expression of
      CD147 with MCT1 was associated with lymph-node and/or distant metastases in
      adenocarcinomas. Our results show a close association between CD147 and MCT1 and
      MCT4 expressions in human cervical cancer and provided evidence for a prognostic
      value of CD147 and MCT1 co-expression.

PMID- 19597293
TI  - A splice variant of GNB3 and peripheral polyneuropathy in type 1 diabetes.
AB  - Abnormalities in G protein-mediated signal transduction could be involved in the
      pathogenesis of diabetic polyneuropathy (DPN). Here we test whether the GNB3
      C825T variant confers susceptibility to DPN in type 1 diabetes (T1D) mellitus.
      The C825T marker of GNB3 was genotyped in genomic DNA from blood isolated from a
      total of 213 Russian T1D patients 100 of whom had DPN. Compared to carriers of
      the wild-type genotype C/C, diabetic subjects with genotypes T/T had
      significantly increased risk to develop DPN (Odds Ratio (OR) of 4.4 (p = 0.001).
      The adjustment for confounders (age, sex, body mass index, cigarette smoking, and
      level of reduced glutathione) resulted in increase of the OR value up to 4.72 (p
      = 8.9 x 10<formula>;{-3}</formula>). The further adjustment for hypertension
      abolished the association between the GNB3 C825T variant and DPN (OR = 1.95, p =
      0.18). Non-complicated subjects homozygous for T/T showed decreased levels of
      reduced glutathione (T/T: 69 +/- 19 vs. C/T: 74 +/- 19 vs. C/C: 77 +/- 17
      micromol/l, p = 0.009). Compared to other GNB3 variants, carriers of the T/T
      genotype had elevated systolic blood pressure (SBP) in complicated (T/T: 115.8 +/
      9.1 vs. C/T: 113.3 +/- 8.2 vs. C/C: 109.5 +/- 8.7 mm/Hg, p = 0.036) and non
      complicated T1D patients (T/T: 118.1 +/- 8.4 vs. C/T: 116.9 +/- 7.9 vs. C/C:
      112.1 +/- 7.2 mm/Hg, p = 0.02). However, the significance of association between
      the C825T polymorphism was lost after adjustment for confounding risk factors. In
      conclusion, the 825T allele of GNB3 is likely to accelerate the development of
      DPN through primary effects to SBP and hypertension in subgroups of diabetic
      patients with impaired neurovascular function and advanced oxidative stress.

PMID- 19597292
TI  - HLA-DR in Brazilian patients with polyarteritis nodosa (PAN) and microscopic
      polyangiitis (MPA).
AB  - The aim of this study was to evaluate the frequency and clinical associations of
      HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or
      microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with
      vasculitis classified as PAN or MPA according to the American College of
      Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC)
      nomenclature for vasculitis and EULAR recommendations for conducting clinical
      studies in systemic vasculitis. HLA-DR alleles were typed using polymerase chain
      reaction-amplified DNA, hybridized with sequence-specific low resolution primers.
      DNA obtained from 59 Caucasian healthy blood donors were used as control. In
      order to evaluate if a specific HLA may have influence on the clinical profile of
      those diseases, we also divided the patients according to Birmingham vasculitis
      score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased
      frequency of HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in
      patients with higher disease activity at the time of diagnosis (BVAS >/=22).
      Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03
      (p = 0.011). Patients with gastrointestinal tract involvement had significantly
      increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and B3
      (p = 0.008). In contrast, patients with renal disease, had higher frequency of
      DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of patients
      with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS
      >/=22 (p = 0.038) and FFS >/=1 (p = 0.039) suggesting that this allele is
      associated with more aggressive disease. Antineutrophil cytoplasmic antibodies
      (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11
      or DRB1*12 when compared to ANCA positive patients (p = 0.023). Our results
      suggest that HLA-DR alleles may influence PAN and MPA clinical expression and
      outcome and that in MPA they participate in the mechanisms involved in the
      development to ANCA.

PMID- 19597294
TI  - Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical
      activity. Association with genetic polymorphisms.
AB  - To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1
      1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA
      patients and 60 healthy non-related subjects (HS) matched for age and sex were
      recruited. Soluble adhesion molecules were determined by ELISA technique.
      Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte
      sedimentation rate (ESR) were measured by routine methods. Disability and
      clinical activity was measured with Spanish-HAQ-DI and DAS28 scores,
      respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP
      procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1
      in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA
      group, significant correlations between sVCAM-1 and RF (r = 0.402), ESR (r =
      0.426), Spanish-HAQ-DI (r = 0.276), and DAS28 (r = 0.342) were found, whereas
      sICAM-1 only correlated with RF (r = 0.445). In RA patients, a significant
      association with the 721A allele of ICAM1 polymorphism (p = 0.04), was found. In
      addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p =
      0.038, OR = 2.3, C.I. 1.1-5.0). sVCAM-1 and sICAM-1 serum levels reflected the
      clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism.
      However, the ICAM1 721A allele could be a genetic marker to RA susceptibility.

PMID- 19597295
TI  - Emerging role of endothelial and inflammatory markers in preeclampsia.
AB  - OBJECTIVES: Endothelial disturbance and excess inflammatory response are
      pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical
      diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI
      1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6)
      as inflammatory markers when tested independently or in combinations. MATERIALS
      AND METHODS: We conducted a retrospective study in a cohort of 185 women grouped
      as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma
      levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent
      assays. RESULTS: Median levels and the positivity rates for the investigated
      markers were higher in PE as compared to the other groups (P < 0.0001). Using
      linear regression analysis, the investigated markers were significantly
      correlated regarding healthy non-pregnant vs PE or normotensive pregnant vs PE.
      The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers.
      Combination between the investigated markers revealed absolute sensitivity (100%)
      and reliable specificity especially when PAI-1 was combined with CRP at 83%
      specificity. CONCLUSIONS: Investigated endothelial and inflammatory markers
      revealed sensitive diagnostic test for PE. However, coupled combination between
      PAI-1 with CRP showed superior both sensitivity and specificity which represent a
      promising new approach for detection of PE.

PMID- 19597296
TI  - Retinol binding protein-4 is associated with TNF-alpha and not insulin resistance
      in subjects with type 2 diabetes mellitus and coronary heart disease.
AB  - We studied the association between RBP4 and various markers related to insulin
      resistance and diabetic complications as well as inflammatory markers in Saudi
      population suffering from type 2 diabetes and coronary heart disease. Patients
      with type 2 diabetes were divided into 3 groups according to the type of
      treatment and involvement of coronary artery disease. Serum RBP4, TNF-alpha,
      insulin, CRP, resistin, leptin and adiponectin were analysed in all samples. RBP4
      levels increased significantly in the group of diabetic subjects treated with
      oral hypoglycemic agents and diabetic patients with coronary heart disease (30.2
      +/- 11.8; 33.4 +/- 13.6 respectively), while there was no significant change in
      the other group for diabetic subjects on low-carbohydrate diet (25.1 +/- 10.9)
      compared to control group (22.6 +/- 9.5). RPB4 levels were positively correlated
      with TNF-alpha in the group of diabetic subjects on oral hypoglycemic agents and
      diabetic patients with coronary heart disease (r = 0.52, P < 0.05; r = 0.58, P <
      0.05 respectively). No correlations were found between RBP4 levels and insulin
      resistance in all studied groups. Our findings suggest that serum RBP4 levels is
      associated with pro-inflammatory cytokine (TNF-alpha) and is not associated with
      insulin resistance among patients with type 2 diabetes and coronary heart
      disease.

PMID- 19597297
TI  - Serum cystatin C is a determinant of paraoxonase activity in hemodialyzed and
      renal transplanted patients.
AB  - BACKGROUND: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis,
      and possesses lactonase activity. Decreased PON1 activity was found in
      hemodialyzed and renal transplanted patients. Cystatin C plays a protective role
      in atherosclerosis, and is a new, sensitive marker of renal function. The
      relationship between these two markers in renal failure has not been
      investigated. AIMS: The goal of this study was to clarify the relationship
      between PON1 activity, cystatin C and homocysteine in chronic renal failure. We
      also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric
      acid reactive substances (TBARS) to characterize lipid peroxidation. PATIENTS AND
      METHODS: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110
      healthy controls (C) were involved in the study. PON1 activity and TBARS levels
      were measured spectrophotometrically. OxLDL level was determined with sandwich
      ELISA. RESULTS: There was a negative correlation between PON1 activity and
      cystatin C level. Homocysteine level correlated negatively with PON1 activity,
      and positively with cystatin C level. OxLDL and TBARS levels were significantly
      higher in the HD and TRX groups compared to C. CONCLUSIONS: Cystatin C may be a
      good predictive factor not only for homocysteine levels but for the antioxidant
      status in patients with renal failure and renal transplantation.

PMID- 19597298
TI  - Prognostic significance of cystatin C in patients with ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Cystatin C is reportedly a better endogenous marker of glomerular
      filtration rate than serum creatinine, so the prognostic value of cystatin C in
      patients with ST-elevation myocardial infarction (MI) was evaluated in the
      present study. METHODS AND RESULTS: A total of 71 patients who underwent
      percutaneous coronary intervention for ST-segment elevation MI <24 h from symptom
      onset were included. According to cystatin C level, patients were classified into
      2 groups: (1) higher cystatin C group (n=33) and (2) lower cystatin C group
      (n=38). There was a trend toward more in-hospital deaths in patients with the
      higher cystatin C level compared with the lower cystatin C level group (15.2% vs
      2.6%, P=0.06). Mean duration of clinical follow-up was 5.6 +/-2.8 months. There
      was no significant difference in death, reinfarction, disabling stroke or target
      lesion revascularization between the 2 groups. However, a higher incidence of
      rehospitalization for congestive heart failure was observed in patients with the
      higher cystatin C level than in those with the lower cystatin C level (15.2% vs
      0%, P=0.01). CONCLUSIONS: Cystatin C may be associated with more cardiovascular
      events, mainly rehospitalization for congestive heart failure, after percutaneous
      coronary intervention in patients with ST-elevation MI.

PMID- 19597299
TI  - Role of the phosphatidylinositol 3-kinase/protein kinase B pathway in regulating
      alternative splicing of tissue factor mRNA in human endothelial cells.
AB  - BACKGROUND: Tissue factor (TF) is the primary initiator of blood coagulation. In
      response to tumor necrosis factor (TNF)-alpha human umbilical vein endothelial
      cells (HUVECs) express 2 TF isoforms: a soluble alternatively spliced isoform
      (asHTF) and membrane-bound "full length" (fl)TF. How the differential TF isoform
      expression is regulated is still unknown. This study compared the impact of
      PI3K/Akt pathway inhibition on alternative splicing of TF in HUVECs, to the
      influence of transcriptional regulation by inhibiting nuclear factor kappa B
      (NFkappaB). METHODS AND RESULTS: The mRNA expression of TF isoforms was assessed
      by real-time PCR, the thrombogenic activity was measured by a chromogenic TF
      activity assay and the phosphorylation state of serine/arginine-rich (SR)
      proteins was analyzed by western blotting. Transfection of HUVECs was done 72 h
      before the inhibition experiments were performed. PI3K/Akt pathway inhibition
      reduced the mRNA expression of asHTF but not flTF. Inhibition of NFkappaB reduced
      the expression of both isoforms. Moreover, the PI3K/Akt pathway inhibition, but
      not that of NFkappaB, modified the phosphorylation of the SR proteins SRp75,
      SRp55 and SF2/ASF. Additionally, overexpression of SF2/ASF and SRp75 influenced
      the differential TF-isoform expression in HUVECs. CONCLUSIONS: The PI3K/Akt
      pathway modulates alternative splicing of TF in HUVECs, distinct from
      transcriptional regulation.

PMID- 19597300
TI  - Age-dependent clinical characteristics of micturition syncope.
AB  - BACKGROUND: Clinical features of micturition syncope (MS) seem to be differ
      according to age and the present study sought to clarify this. METHODS AND
      RESULTS: The 37 consecutive patients (mean age: 52.2 +/-16.8 years, 26 men) with
      MS were divided into 2 groups by median age of 55: younger group (YG) consisting
      of 18 patients <55 years (average 38.2) and an older group (OG) consisting of 19
      patients >or=55 years (average 65.5). Alcohol-related MS was significantly more
      frequent in the YG than in the OG (78% vs 42%, P=0.027). Daily distribution of MS
      was significantly different (P=0.0009): 85% of the MS in the YG occurred before
      midnight (PM), whereas 75% of the MS in the OG occurred after midnight (AM).
      Although overall positive responses of head-up tilt testing were more common in
      the OG (P=0.046), gender, number of syncope, and association with vasovagal
      syncope or cardiovascular disease were not different between both groups.
      CONCLUSIONS: In the YG, MS tended to occur in the evening or nighttime before
      midnight, whereas MS in the OG tended to occur after midnight or early in the
      morning. Alcohol intake may be an important precipitating factor for MS in young
      subjects.

PMID- 19597301
TI  - Relationship of maximum rate of pressure rise between aorta and left ventricle in
      pediatric patients. Implication for ventricular-vascular interaction with the
      potential for noninvasive determination of left ventricular contractility.
AB  - BACKGROUND: The maximum rate of the ventricular pressure rise (dp/dt(max))
      provides a reliable measure of ventricular contractility. However, its estimation
      requires invasive measurement of left ventricular (LV) pressure, limiting its
      bedside clinical applicability. In the present study, 2 hypotheses were tested:
      (1)that the ratio of dp/dt(max) between the aorta (Ao) and LV is consistent among
      patients despite marked differences in underlying cardiac disease, contractile
      state and heart rate when vascular mechanical and loading properties are taken
      into account, and (2)that using such a relationship, LV dp/dt(max) can be
      estimated from Ao dp/dt(max), potentially providing a method of noninvasive
      determination of LV contractility. METHODS AND RESULTS: Data from 30 control
      children and 45 pediatric patients with various cardiovascular diseases revealed
      that the characteristic impedance (Zc) and mean arterial pressure were
      significant determinants of the Ao-LV dp/dt(max) relationship in both control and
      disease groups. LV dp/dt(max) estimated using the regression obtained in the
      control children (Ao dp/dt(max/)LV dp/dt(max) = 0.64+1.45*10(-4)*Zc-3.73*10(
      3)*MAP, r=0.87) correlated well with the measured LV dp/dt(max) in the disease
      group, including measurements taken after dobutamine and atrial pacing (r=0.89).
      CONCLUSIONS: Ao dp/dt(max) and LV dp/dt(max) are closely correlated through the
      vascular loading properties and LV dp/dt(max) can be derived from Ao dp/dt(max),
      which has potential as a noninvasive method of determining LV contractility.

PMID- 19597302
TI  - Successful treatment of crush syndrome complicated with multiple organ
      dysfunction syndrome using hybrid continuous renal replacement therapy.
AB  - BACKGROUND: The M8.1 'Wenchuan' earthquake occurred on May 12th 2008 causing many
      injuries and casualties. We report a case with crush syndrome and multiple organ
      dysfunction syndrome (MODS) successfully treated with hybrid continuous renal
      replacement therapy (CRRT). METHOD: The patient is a 16-year-old female who was
      rescued from a collapsed building after 17 h. Emergency amputation was performed.
      Infections and crush syndrome caused sepsis, acute respiratory distress syndrome,
      acute renal failure, heart failure, liver dysfunction and disseminated
      intravascular coagulation in a short time. Hybrid CRRT including high volume
      hemofiltration, low temperature blood purification, hemoperfusion using endotoxin
      adsorbent as well as plasmapheresis was performed. RESULT: After the hybrid CRRT
      treatment, the patient's condition improved progressively. Functions of lung,
      heart, liver and kidney recovered. Sepsis was controlled. CRRT treatment
      continued for 550 h without stop. She was followed up for 6 months without any
      sign of residual organ dysfunction. CONCLUSION: Hybrid CRRT is an effective
      treatment for patients with severe crush syndrome complicated with MODS.

PMID- 19597303
TI  - Regulation of cytokine signaling by the SOCS and Spred family proteins.
AB  - Various cytokines are involved in the regulation of the immune system and of
      hematopoiesis. Most cytokines utilize the so-called JAK-STAT pathway, but others
      activate the Ras-ERK pathway, which is more important than the STAT pathway for
      the proliferation of hematopoietic cells. Dysregulation of cytokine signaling can
      cause a variety of diseases, including allergy, inflammation, and cancer. We have
      identified two important regulator families involved in cytokine signaling: the
      SOCS proteins and the Spred proteins. Suppressors of cytokine signaling (SOCS)
      proteins bind to JAK and to certain receptors, thereby suppressing further
      signaling events. Spred family proteins interact with Ras and Raf, thereby
      suppressing ERK activation. Studies have shown that SOCS and Spred proteins are
      key physiological regulators of immunity, hematopoiesis, and angiogenesis.
      Evidence is also emerging for the involvement of these proteins in human
      diseases.

PMID- 19597304
TI  - Perspectives in medical education 7. Observations on clinical training at a "US
      style" residency program at Teine Keijinkai Hospital in Sapporo, Japan.
AB  - The residency program at Teine Keijinkai Hospital in Sapporo has successfully
      implemented a training philosophy that is focused on the development of clinical
      skills and critical thinking in Japanese residents. Several elements contribute
      to its success. The first and foremost is visionary physician leadership,
      beginning with the pioneers who implemented the philosophy, and continuing
      through the current leadership, which has sustained the original vision. A close
      second is the administrative and financial commitment to invest in producing more
      clinically accomplished Japanese physicians, long before that need was officially
      recognized. Third is the program's explicit aim of adhering to international
      norms by requiring three years of training, promulgating a benevolent, not
      paternalistic teaching philosophy and encouraging an interactive and
      interrogatory learning ethic. Fourth is the year-round presence of a US-trained
      Physician-in-Residence, to sustain the focus on clinical skills and international
      norms. Fifth is a long-term relationship with the Internal Medicine Training
      Program at the University of Pittsburgh, providing a conduit for ongoing academic
      exchange and programmatic advice. Last, but not least, is its avowed intention of
      being viewed as an "American-style program" with a preference for English fluent
      applicants, which acts as a magnet for trainees motivated to acquire clinical
      skills and competencies, with an eye to future training in the US. All these
      elements contribute to the program's unique focus on teaching clinical skills and
      critical thinking. Others who are striving with varying degrees of success to
      implement a similar philosophy in Japan may benefit from studying its example.

PMID- 19597305
TI  - Suicide in adolescents: a worldwide preventable tragedy.
AB  - The tragedy of suicide in adolescents is experienced by all countries of the
      world with as many as 200,000 youth and young adults ending their life in the
      prime of their life because of self-murder each year. Such a tragedy should be
      unacceptable to clinicians of the world and this article examines factors leading
      to such death in our youth with recommendations on how to prevent such a
      worldwide carnage. A major issue in suicide prevention is to screen all children
      and adolescents for depression and other factors that may trigger suicide in
      adolescence.

PMID- 19597306
TI  - Pancreatectomy for pancreatic cancer with reference to combined resection of the
      vessels, twenty nine year experience by a single surgeon.
AB  - Between 1978 and 2007 one hundred and seven patients consecutively underwent
      resection for primary pancreatic adenocarcinoma. There were 28 pN0 patients, 41
      pN1 and 37 pN2 or more (one unknown). Combined resection of the portal vein was
      performed in 62 out of 107 patients (58%). The hepatic artery in 10 patients,
      superior mesenteric artery in 8 patients and celiac trunk in 7 patients were also
      resected additionally to the portal vein. The 5-year survival rate and 10-year
      survival rate of all 107 cases were 12.1% and 2.8% respectively. The 5-year
      survival rate of the pN0 group was 37%, significantly better than the 14% 5-year
      survival rate in the pN1 group (p=0.043). Of 69 patients with pN0 or pN1, 38
      patients underwent combined resection of the portal vein. There was not
      significant difference between the 24% 5-year survival rate in the group without
      the portal vein resection and the 19% 5-year survival rate in the group with
      portal vein resection. The 20% 5-year survival rate of the portal vein only group
      and the 5-year survival rate of both the portal vein and hepatic artery group
      were the same. The groups of the further resection of the superior mesenteric
      artery and of the celiac trunk showed no long-term survival. It is concluded that
      aggressive combined resection of the portal vein or additional resection of the
      hepatic artery be feasible for a survival benefit in pN0 and pN1 diseases.

PMID- 19597307
TI  - An inquiry about clinical death--considering spiritual pain.
AB  - According to a paper published by the International Work Group on Death, Dying
      and Bereavement, "Each person has a spiritual dimension." That means each person
      has spiritual energy and spiritual needs. In facing death, a patient suffers
      spiritual pain and needs spiritual care. This paper describes what spirituality
      and spiritual pain mean. It identifies nine types of fears and anxieties about
      death which become a source of spiritual pain: 1. Fear of pain; 2. Fear of
      loneliness; 3. Fear of unpleasant experiences; 4. Fear of becoming a burden to
      the family and to society; 5. Anxiety towards the unknown; 6. Fear of death
      resulting from fear of life; 7. Fear of death as a feeling that one's life task
      is still incomplete; 8. Fear of death as fear of personal extinction; 9. Fear of
      death as fear of judgment and punishment after death. Five types of spiritual
      pain that seem to be frequent among patients facing death are discussed: 1. Loss
      of self-determination; 2. Loss of meaning; 3. Guilt feelings; 4. Loneliness and
      isolation; 5. Loss of hope. Three ways of preventing or reducing excessive fear
      of death and of lowering the various types of spiritual pain are suggested: 1.
      Death education; 2. Presence at the bedside; 3. Humor as an expression of love.

PMID- 19597308
TI  - Stereotactic radiosurgery with an upper partial denture.
AB  - A 54-year-old male with partial denture underwent stereotactic radiosurgery with
      an infrared camera-guided system for a metastatic brain tumor arising from lung
      cancer. Although this method utilizes a biteplate mounted on the upper jaw to
      detect head movement, the patient only had four teeth in his upper jaw. In order
      to stabilize the biteplate, the maxillary denture was fixed to the biteplate with
      an autopolymerizing resin. In addition, the rest-occlusal position of the lower
      jaw was impressed on the inferior surface of the biteplate with an
      autopolymerizing resin. To assess reproducibility and stability, the distance
      between the left and right incus and left and right markers was measured during
      pre-planning, as well as before and after stereotactic irradiation. Wearing the
      biteplate ensures the accuracy of radiotherapy planning for the implementation of
      radiosurgery in patients who have many maxillary teeth missing. However, a large
      degree of error was observed when the biteplate was removed.

PMID- 19597309
TI  - Selective sterilization of Vibro parahaemolyticus from a bacterial mixture by low
      amperage electric current.
AB  - The objective of this study was to investigate the possibility of using low
      amperage electrical treatment (LAET) as a selective bacteriocide. Mixtures
      containing Escherichia coli, Staphylococcus aureus, and Vibrio parahaemolyticus
      were treated with different electric current intensities and for different times.
      The results showed that at 263 mA, treating bacteria for 100 ms eliminated all V.
      parahaemolyticus colonies. Although LAET reduced the populations of the three
      microorganisms, V. parahaemolyticus was more injured by LAET than S. aureus and
      E. coli when treated at the same processing conditions.

PMID- 19597310
TI  - Ecotype-dependent genetic regulation of bolting time in the Arabidopsis mutants
      with increased number of leaves.
AB  - Leaves are the major biomass-producing organs in herbaceous plants and mainly
      develop during vegetative stage by activities of shoot apical meristem. There is
      a strong correlation between leaf number and bolting, a characteristic phenotype
      during the transition to reproductive phase in Arabidopsis thaliana. In order to
      study interactions between leaf number and bolting, we isolated a Landsberg
      erecta-derived mutant named multifolia1 (mfo1) that produces increased number of
      leaves and bolts at the same time as the wild type. Through positional cloning
      and allelism test, mfo1 was found to be an allele of a previously reported
      mutant, altered meristem program1-1 (amp1-1) that is defective in a glutamate
      carboxypeptidase and bolts earlier than its wild type, Columbia ecotype, with the
      increased number of leaves. The bolting time differences between mfo1 and amp1,
      despite the same phenotype of many leaves, suggest the existence of genetic
      factor(s) differently function in each ecotype in the presence of mfo1/amp1
      mutation.

PMID- 19597311
TI  - Nanoscopic morphological changes in yeast cell surfaces caused by oxidative
      stress: an atomic force microscopic study.
AB  - Nanoscopic changes in the cell surface morphology of the yeasts Saccharomyces
      cerevisiae (strain NCYC 1681) and Schizosaccharomyces pombe (strain DVPB 1354),
      due to their exposure to varying concentrations of hydrogen peroxide (oxidative
      stress), were investigated using an atomic force microscope (AFM). Increasing
      hydrogen peroxide concentration led to a decrease in cell viabilities and mean
      cell volumes, and an increase in the surface roughness of the yeasts. In
      addition, AFM studies revealed that oxidative stress caused cell compression in
      both S. cerevisiae and Schiz. pombe cells and an increase in the number of aged
      yeasts. These results confirmed the importance and usefulness of AFM in
      investigating the morphology of stressed microbial cells at the nanoscale. The
      results also provided novel information on the relative oxidative stress
      tolerance of S. cerevisiae and Schiz. pombe.

PMID- 19597312
TI  - NF-kappaB Activation by compounds found in Platycodon grandiflorum extract.
AB  - Compounds extracted from Platycodon grandiflorum were evaluated for an activation
      effect on nuclear factor-kappa B (NF-kappaB). In its active state, NF-kappaB
      turns on the expression of genes related to cell proliferation or death. NF
      kappaB activators promote growth of neuron cells and can be used to control
      neurodegenerative diseases. The biological activity of P. grandiflorum extracts
      toward NF-kappaB had not yet been studied. Although the biological activity of
      several compounds extracted from P. grandiflorum was evaluated, only three
      exhibited any significant activation effect on NF-kappaB.

PMID- 19597313
TI  - Gibberellin production and plant growth enhancement by newly isolated strain of
      Scolecobasidium tshawytschae.
AB  - We isolated nine endophytic fungi from the roots of saltstressed soybean cultivar
      Daewonkong and screened them for growth-promoting secondary metabolites. Of all
      fungal isolates, P-4-3 induced maximum growth promotion of waito-c rice and
      soybean. Analysis of the culture filtrate of P-4-3 showed the presence of
      physiologically active gibberellins GA1, GA3, GA4, and GA7, along with
      physiologically inactive GA15 and GA24. The plant growth promotion and
      gibberellinproducing capacity of P-4-3 was much higher than wildtype Gibberella
      fujikuroi, which was taken as the control during the present study. The fungal
      isolate P-4-3 was identified as a new strain of Scolecobasidium tshawytschae
      through the morphological characteristics and phylogenetic analysis of 18S rDNA
      sequence. Gibberellins production and plant growth promoting ability of genus
      Scolecobasidium was reported for the first time in the present study.

PMID- 19597314
TI  - Study on immunostimulating activity of macrophage treated with purified
      polysaccharides from liquid culture and fruiting body of Lentinus edodes.
AB  - Lentinus edodes is a well-known edible and medicinal mushroom used in Oriental
      cultures. Recently, L. edodes has attracted a lot of attention owing to its
      antifungal activity, antibacterial activity, antiviral activity, hepatoprotective
      effect, antitumor activities, and immunomodulatory and cytotoxic effects. In this
      study, the water-soluble crude polysaccharides, CPF and CPB, which were obtained
      from the fruiting body and culture cell-free broth of L. edodes by hot-water
      extraction and ethanol precipitation, were fractionated by DEAE cellulose and
      Sepharose CL-6B column chromatography, resulting in six polysaccharide fractions,
      CPFN-G-I, CPFN-G-II, CPFN-G-III, CPFA-G, CPBN-G, and CPBA-G. Among these
      fractions, CPFN-GI, CPBN-G, and CPBA-G were shown to stimulate the functional
      activation of macrophages including NO production cytokine expression and
      phagocytosis.

PMID- 19597315
TI  - Plant cell wall degradation with a powerful Fusarium graminearum enzymatic
      arsenal.
AB  - The complex enzyme pool secreted by the phytopathogenic fungus Fusarium
      graminearum in response to glucose or hop cell wall material as sole carbon
      sources was analyzed. The biochemical characterization of the enzymes present in
      the supernatant of fungal cultures in the glucose medium revealed only 5
      different glycosyl hydrolase activities; by contrast, when analyzing cultures in
      the cell wall medium, 17 different activities were detected. This dramatic
      increase reflects the adaptation of the fungus by the synthesis of enzymes
      targeting all layers of the cell wall. When the enzymes secreted in the presence
      of plant cell wall were used to hydrolyze pretreated crude plant material, high
      levels of monosaccharides were measured with yields approaching 50% of total
      sugars released by an acid hydrolysis process. This report is the first
      biochemical characterization of numerous cellulases, hemicellulases, and
      pectinases secreted by F. graminearum and demonstrates the usefulness of the
      described protein cocktail for efficient enzymatic degradation of plant cell
      wall.

PMID- 19597316
TI  - Production of acrylic acid from Acrylonitrile by immobilization of Arthrobacter
      nitroguajacolicus ZJUTB06-99.
AB  - Immobilized cells of Arthrobacter nitroguajacolicus ZJUTB06-99 capable of
      producing nitrilase was used for biotransformation of acrylonitrile to acrylic
      acid. Six different entrapment matrixes were chosen to search for a suitable
      support in terms of nitrilase activity. Ca-alginate proved to be more
      advantageous over other counterparts in improvement of the biocatalyst activity
      and bead mechanical strength. The effects of sodium alginate concentration, CaCl2
      concentration, bead diameter, and ratio by weight of cells to alginate, on
      biosynthesis of acrylic acid by immobilized cells were investigated. Maximum
      activity was obtained under the conditions of 1.5% sodium alginate concentration,
      3.0% CaCl2 concentration, and 2-mm bead size. The beads coated with 0.10%
      polyethylenimine (PEI) and 0.75% glutaraldehyde (GA) could tolerate more
      phosphate and decrease leakage amounts of cells from the gel. The beads treated
      with PEI/ GA could be reused up to 20 batches without obvious decrease in
      activities, which increased about 100% compared with the untreated beads with a
      longevity of 11 batches.

PMID- 19597317
TI  - Screening and identification of a Streptomyces platensis YK-2, a new
      transglutaminase producer.
AB  - A bacterial strain, YK-2, was isolated as a producer of transglutaminase from a
      forest soil sample of Daegu, Korea. The isolate showed a G+C content of 72.7
      mol%, contained meso-A(2)pm as the cell-wall amino acid, and possessed
      menaquinone MK-9 (H(6)) and menaquinone MK-9 (H8) at a ratio of 6:4. The
      chemotaxonomic analysis, as well as phylogenetic analysis based on the 16S rDNA
      sequence, identified the isolate as a member of Streptomyces platensis. For
      transglutaminase production, the optimum medium composition was determined to be
      2% glucose, 1% polypeptone, 1% soytone, and 0.1% MnCl(2). The transglutaminase
      was stable within the pH range of 5.0- 9.0 and 30-45 degrees , and the optimum pH
      and temperature were pH 8.0 and 45 degrees, respectively, without any requirement
      for Ca(2+).

PMID- 19597318
TI  - Enhancement of hyaluronic acid production by batch culture of Streptococcus
      zooepidemicus with n-dodecane as an oxygen vector.
AB  - This study aimed to examine the influence of adding an oxygen vector, n-dodecane,
      on hyaluronic acid (HA) production by batch culture of Streptococcus
      zooepidemicus. Owing to the high viscosity of culture broth, microbial HA
      production during 8-16 h was limited by the oxygen transfer coefficient K(L)a,
      which could be enhanced by adding n-dodecane. With the addition of n-dodecane to
      the culture medium to a final concentration of 5% (v/v), the average value of
      K(L)a during 8-16 h was increased to 36+/-2 h(-1), which was 3.6 times that of
      the control without n-dodecane addition. With the increased K(L)a and dissolved
      oxygen (DO) by adding 5% (v/v) of n-dodecane, a 30% increase of HA production was
      observed compared with the control. Furthermore, the comparison of the oxygen
      mass transfer in the absence and presence of n-dodecane was conducted with two
      proposed mathematical models. The use of n-dodecane as an oxygen vector, as
      described in this paper, provides an efficient alternative for the optimization
      of other aerobic biopolymer productions,where K(L)a is usually a limiting factor.

PMID- 19597319
TI  - Potential application of the recombinant Escherichia coli-synthesized heme as a
      bioavailable iron source.
AB  - To investigate the potential use of microbial heme as an iron source, recombinant
      Escherichia coli coexpressing ALA synthase (HemA) as well as the NADP-dependent
      malic enzyme (MaeB) and dicarboxylic acid transporter (DctA) were cultured. The
      typical red pigment extracted from the recombinant E. coli after 38 h showed
      highest absorbance at 407 nm, and the amount of iron in 38.4 mg of microbial heme
      extract derived from 6-l fermentation broth was 4.1 mg. To determine the
      commercial potential of the recombinant E.coli-synthesized iron-associated heme
      as an iron source, mice were fed the iron-free provender with the microbial heme
      extract. The average body weight reduction of mice fed non-iron provender was
      2.3%, whereas no detectable weight loss was evident in mice fed microbial heme
      addition after 15 days. The heme content of the blood from microbial heme fed
      mice was 4.2 mg/ml whereas that of controls was 2.4 mg/ml, which implies that the
      microbial heme could be available for use as an animal iron source.

PMID- 19597320
TI  - A technique of segment expression and RNA interference (SERI) reveals a specific
      physiological function of a cysteine-rich protein gene encoded in cotesia
      plutellae bracovirus.
AB  - As a provirus, polydnavirus has a segmented DNA genome on chromosome(s) of host
      wasp. It contains several genes in each segment that presumably play critical
      roles in regulating physiological processes of target insect parasitized by the
      wasp. A cysteine-rich protein 1 (CRP1) is present in the polydnavirus Cotesia
      plutellae bracovirus (CpBV) genome, but its expression and physiological function
      in Plutella xylostella parasitized by the viral host C. plutellae is not known.
      This CpBV-CRP1 encoding 189 amino acids with a putative signal peptide (20
      residues) was persistently expressed in parasitized P. xylostella with gradual
      decrease at the late parasitization period. Expression of CpBV-CRP1 was tissue
      specific in the fat body/epidermis and hemocyte, but not in the gut. Its
      physiological function was analyzed by inducing transient expression of a CpBV
      segment containing CpBV-CRP1 and its promoter, which caused significant reduction
      in hemocyte -spreading and delayed larval development. When the treated larvae
      were co-injected with double-stranded RNA of CpBV-CRP1, the expression of CpBV
      CRP1 disappeared,whereas other genes encoded in the CpBV segment was expressed.
      These co-injected larvae significantly recovered the hemocyte-spreading capacity
      and larval development rate. This study reports that CpBV-CRP1 is expressed in
      P.xylostella parasitized by C.plutellae and its physiological function is to
      alter the host immune and developmental processes.

PMID- 19597321
TI  - Glycosaminoglycan degradation-inhibitory lactic acid bacteria ameliorate 2,4,6
      trinitrobenzenesulfonic acid-induced colitis in mice.
AB  - To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel
      diseases (IBD), we measured the inhibitory effect of several LAB isolated from
      intestinal microflora and commercial probiotics against the glycosaminoglycan
      (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and
      Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB
      inhibited colon shortening and myeloperoxidase production in 2,4,6-
      trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB
      also blocked the expression of the proinflammatory cytokines, IL-1beta and TNF
      alpha, as well as of COX-2, in the colon. LAB also blocked activation of the
      transcription factor, NF-kappaB, and expression of TLR-4 induced by TNBS. In
      addition, LAB reduced the TNBS-induced bacterial degradation activities of
      chondroitin sulfate and hyaluronic acid. These findings suggest that GAG
      degradation-inhibitory LAB may improve colitis by inhibiting inflammatory
      cytokine expression via TLR-4-linked NF-kB activation and by inhibiting
      intestinal bacterial GAG degradation.

PMID- 19597322
TI  - Efficacy of bacteriophage treatment in murine burn wound infection induced by
      klebsiella pneumoniae.
AB  - In the present study, the therapeutic potential of purified and well
      characterized bacteriophages was evaluated in thermally injured mice infected
      with Klebsiella pneumoniae B5055. The efficacy of five Klebsiella phages (Kpn5,
      Kpn12, Kpn13, Kpn17, and Kpn22) was evaluated on the basis of survival rate,
      decrease in bacterial counts in different organs of phage-treated animals, and
      regeneration of skin cells as observed by histopathological examination of phage
      treated skin. Toxicity studies performed with all the phages showed them to be
      non-toxic, as no signs of morbidity and mortality were observed in phage-treated
      mice. The results of the study indicate that a single dose of phages,
      intraperitoneally (i.p.) at an MOI of 1.0, resulted in significant decrease in
      mortality, and this dose was found to be sufficient to completely cure K.
      pneumoniae infection in the burn wound model. Maximum decrease in bacterial
      counts in different organs was observed at 72 h post infection. Histopathological
      examination of skin of phage-treated mice showed complete recovery of burn
      infection. Kpn5 phage was found to be highly effective among all the phages and
      equally effective when compared with a cocktail of all the phages. From these
      results, it can be concluded that phase therapy may have the potential to be used
      as stand-alone therapy for K.pneumoniae induces burn wound infection, especially
      in situations where multiple antibiotic-resistant organisms are encountered.

PMID- 19597323
TI  - Suppression of metastasis of human breast cancer cells by chitosan
      oligosaccharides.
AB  - The present study investigated the antimetastatic property of chitosan
      oligosaccharides (COS) by evaluating motility, invasion, and the amount and
      activity of MMP-9 in MDA-MB-231 human breast carcinoma cells. Treatment of MDA-MB
      231 cells with increasing concentrations of COS led to a concentration-dependent
      decrease in cell migration. COS significantly inhibited the invasion of MDA-MB
      231 cells through a Matrigel-coated membrane. The treatment of MDA-MB-231 cells
      with COS reduced the amounts of secreted MMP-9. The activity and amount of MMP-9
      protein in MDA-MB-231 cells were decreased by treatment with COS and occurred in
      a concentration-dependent manner. Our data indicated that COS can serve as a
      potential novel therapeutic candidate for the treatment of metastatic breast
      cancer.

PMID- 19597328
TI  - Role of the protein kinase Kin1 and nuclear centering in actomyosin ring
      formation in fission yeast.
AB  - Cytokinesis is the last step of the cell cycle, producing two daughter cells
      inheriting equal genetic information. This process involves the assembly of an
      actomyosin ring during mitosis. In the fission yeast Schizosaccharomyces pombe,
      cytokinesis occurs at the geometric cell centre, a position which is defined by
      the interphase nucleus and the anilin-related Mid1 protein. The pom1Delta,
      tea1Delta and tea4Delta mutants are defective in restricting Mid1 as a band
      around the nucleus and misplace the division site. We previously reported that
      inhibition of the protein kinase Kin1 promoted failure of cytokinesis in
      pom1Delta and tea1Delta cells but the mechanism involving Kin1 remained elusive.
      Here we investigated the contribution of Kin1 in cytokinesis. We show that Kin1
      GFP has a dynamic cell cycle regulated distribution. Like pom1Delta and
      tea1Delta, tea4Delta exhibits a strong genetic interaction with kin1Delta. Using
      a conditional repressible kin1 allele that only alters interphase nuclear
      centering, we observed that Kin1 downregulation severely compromised actomyosin
      ring formation and septum synthesis in tea4Delta cells. In addition, nuclear
      displacement induced either by overexpression of a putative catalytically
      inactive Kin1 mutant, by chemically mediated microtubule depolymerization or by
      mutation in the par1Delta gene impaired cytokinesis in tea4Delta but not tea4(+)
      cells. We propose that nuclear mispositioning exacerbates the tea4Delta,
      pom1Delta and tea1Delta cell division phenotype. Our work reveal that nuclear
      centering becomes essential when Pom1/Tea1/Tea4 function is compromised and that
      Kin1 expression level is a key regulatory element in this situation. Our results
      suggest the existence of distinct overlapping control mechanisms to ensure
      efficient cell division.

PMID- 19597327
TI  - The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but
      distinct pathways to control cell cycle quiescence during C. elegans development.
AB  - Cyclin-dependent kinase inhibitors (CKIs) are major contributors to the decision
      to enter or exit the cell cycle. The Caenorhabditis elegans genome encodes two
      CKIs belonging to the Cip/Kip family, cki-1 and cki-2. cki-1 has been shown to
      act as a canonical negative regulator of cell cycle entry, while the role of cki
      2 remains unclear. We identified cki-2 in a genome-wide RNAi screen to reveal
      genes essential for developmental cell cycle quiescence. Examination of cki-2
      knockout animals revealed extra rounds of cell divisions, verifying a role in
      establishing or maintaining the temporary cell cycle arrest. Despite the
      overlapping defects, the pathways mediated by cki-1 and cki-2 are discrete since
      the extra cell phenotype conferred by a putative cki-2(null) mutation is enhanced
      upon additional loss of cki-1 activity. Moreover, the extra cell division defect
      of cki-2 is not increased with the additional loss of lin-35 Rb, as is seen with
      cki-1. Thus, both cki-1 and cki-2 mediate cell cycle quiescence, but our genetic
      and phenotypic analyses demonstrate that they act within distinct pathways to
      exert control over the cell cycle machinery.

PMID- 19597329
TI  - Structural polymorphism of Alzheimer Abeta and other amyloid fibrils.
AB  - Deposits of amyloid fibrils characterize a diverse group of human diseases that
      includes Alzheimer's disease, Creutzfeldt-Jakob disease and type II diabetes.
      Amyloid fibrils formed from different polypeptides contain a common cross-beta
      spine. Nevertheless, amyloid fibrils formed from the same polypeptide can occur
      in a range of structurally different morphologies. The heterogeneity of amyloid
      fibrils reflects different types of polymorphism: (i) variations in the
      protofilament number, (ii) variations in the protofilament arrangement and (iii)
      different polypeptide conformations. Amyloid fibril polymorphism implies that
      fibril formation can lead, for the same polypeptide sequence, to many different
      patterns of inter- or intra-residue interactions. This property differs
      significantly from native, monomeric protein folding reactions that produce, for
      one protein sequence, only one ordered conformation and only one set of inter
      residue interactions.

PMID- 19597330
TI  - Cap in hand: targeting eIF4E.
AB  - Recognition of the mRNA cap structure by the translation initiation factor eIF4E
      is central to protein synthesis in general and eIF4E activity is especially
      important for the production of many of the proteins that give rise to the
      hallmarks of cancer. Because transformed cells have a heightened requirement for
      the expression of prosurvival factors, targeting translation appears to be an
      attractive anticancer strategy and proof-of-concept studies in which oncogenic
      eIF4E function is suppressed in various different ways show that tumour cells are
      selectively sensitive to inhibition of protein synthesis at the level of eIF4E.
      The emerging understanding of the functions, regulation, and structural biology
      of eIF4E now makes possible the pharmacological targeting of this key translation
      initiation factor.

PMID- 19597331
TI  - Making cortex in a dish: in vitro corticopoiesis from embryonic stem cells.
AB  - The cerebral cortex is arguably the most complex structure in the mammalian
      brain. It develops through the coordinated generation of dozens of neuronal
      subtypes, but the mechanisms involved in this daunting process of cell
      diversification remain poorly understood. We recently described a novel pathway
      by which mouse embryonic stem (ES) cells, cultured in the absence of any added
      morphogen but in the presence of a Sonic Hedgehog inhibitor, can recapitulate the
      major milestones of cortical development observed in vivo. In this system
      cortical-like progenitors seem to follow an intrinsic pathway to generate a
      surprisingly diverse repertoire of neurons that display most salient features of
      bona fide cortical pyramidal neurons. When grafted into the cerebral cortex in
      vivo, these neuronal populations develop patterns of axonal projections highly
      similar to those of native cortical neurons. The discovery of intrinsic
      corticogenesis, from stem cells to cortical circuits, sheds new light on the
      mechanisms of neuronal specification, and may open new venues for the modelling
      of cortical development and diseases, and for the rational design of brain repair
      strategies.

PMID- 19597333
TI  - Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac).
AB  - We studied effects of tetrac (tetraiodothyroacetic acid) on survival of GL261, a
      murine brain tumor cell line, following single doses of 250 kVp x-rays and on
      repair of damage (sublethal and potentially lethal damage repair; SLDR, PLDR) in
      both exponential and plateau phase cells. Cells were exposed to 2 muM tetrac (1 h
      at 37 degrees C) prior to x-irradiation. At varying times after irradiation,
      cells were re-plated in medium without tetrac. Two weeks later, colonies were
      counted and results analyzed using either the linear-quadratic (LQ) or single
      hit, multitarget (SHMT) formalisms. Tetrac sensitized both exponential and
      plateau phase cells to x-irradiation, as shown by a decrease in the quasi
      threshold dose (Dq), leading to an average tetrac enhancement factor (ratio of
      SF2 values) of 2.5. Tetrac reduced SLDR in exponential cells by a factor of 1.8.
      In plateau phase cells there was little expression of SLDR, but tetrac produced
      additional cell killing at 1-4 h after the first dose. For PLDR expression in
      exponential cells, tetrac inhibited PLDR by a factor of 1.9, and in plateau phase
      cells, tetrac decreased PLDR expression by a factor of 3.4. These data show that
      the decreased Dq value seen after single doses of x-rays with tetrac treatment is
      also accompanied by a significant decrease in recovery from sublethal and
      potentially lethal damage.

PMID- 19597334
TI  - Unlike p53, p27 failed to exhibit an anti-tumor genetic interaction with Ku80.
AB  - Ku80 is often referred to as a tumor suppressor since it maintains the genome by
      repairing DNA double-strand breaks (DSBs) via the nonhomologous end joining
      (NHEJ) pathway. Even though Ku80 deletion causes hypersensitivity to gamma
      radiation, DNA damage and chromosomal rearrangements, Ku80-mutant mice exhibit
      very low cancer levels. We previously hypothesized these low cancer levels were
      caused by enhanced cell cycle checkpoints that responded to inefficiently
      repaired DNA damage because Ku80-mutant fibroblasts exhibit premature cellular
      senescence that was dependent on a p53-mediated DNA damage response. In addition,
      Ku80 and p53 show a genetic interaction to suppress pro-B cell lymphoma and
      medulloblastoma. Here we tested for a similar anti-tumor genetic interaction
      between Ku80 and the cyclin kinase inhibitor, p27(Kip1) (p27) since p27 mutant
      mice showed elevated levels of pituitary adenoma that were exacerbated by gamma
      radiation-induced DNA damage (damage repaired by Ku80). We found that deleting
      both Ku80 and p27 did not exacerbate cancer as compared to either single mutant.
      In addition, fibroblasts deleted for both exhibited premature cellular senescence
      similar to Ku80-mutant fibroblasts. Thus, p27 did not exhibit an obvious genetic
      interaction with Ku80 to suppress tumors. This observation suggests that DNA
      damage (or DNA damage responses) induced by either gamma-radiation or Ku80
      deletion are not equivalent since gamma-radiation exacerbates oncogenesis in mice
      deleted for either p53 or p27 while Ku80 deletion exacerbates oncogenesis for
      only the former genotype.

PMID- 19597332
TI  - The Akt kinases: isoform specificity in metabolism and cancer.
AB  - The Akt (PKB) protein kinases are critical regulators of human physiology that
      control an impressive array of diverse cellular functions, including the
      modulation of growth, survival, proliferation and metabolism. The Akt kinase
      family is comprised of three highly homologous isoforms: Akt1 (PKBalpha), Akt2
      (PKBbeta) and Akt3 (PKBgamma). Phenotypic analyses of Akt isoform knockout mice
      documented Akt isoform specific functions in the regulation of cellular growth,
      glucose homeostasis and neuronal development. Those studies establish that the
      functions of the different Akt kinases are not completely overlapping and that
      isoform-specific signaling contributes to the diversity of Akt activities.
      However, despite these important advances, a thorough understanding about the
      specific roles of Akt family members and the molecular mechanisms that determine
      Akt isoform functional specificity will be essential to elucidate the complexity
      of Akt regulated cellular processes and how Akt isoform-specific deregulation
      might contribute to disease states. Here, we summarize recent advances in
      understanding the roles of Akt isoforms in the regulation of metabolism and
      cancer, and possible mechanisms contributing to Akt isoform functional
      specificity.

PMID- 19597335
TI  - Atg101, a novel mammalian autophagy protein interacting with Atg13.
AB  - Autophagy is a major route by which cytoplasmic contents are delivered to the
      lysosome for degradation. Many autophagy-related (ATG) genes have been identified
      in yeast. Although most of them are conserved in human, the molecular composition
      of the Atg1 complex appears to differ between yeast and mammals. In yeast, Atg1
      forms a complex with Atg11, Atg13, Atg17, Atg29 and Atg31, whereas mammalian Atg1
      (ULK1/2) interacts with Atg13 and FIP200. Here, we identify a novel mammalian
      Atg13 binding protein, named Atg101. Atg101 shows no homology with other Atg
      proteins, and is conserved in various eukaryotes, but not in Saccharomyces
      cerevisiae. Atg101 associates with the ULK-Atg13-FIP200 complex, most likely
      through direct interaction with Atg13. In Atg13 siRNA-treated cells, Atg101 is
      present solely as a monomer. Interaction between Atg101 and the ULK-Atg13-FIP200
      complex is stable, and is not regulated by nutrient conditions. GFP-Atg101
      localizes to the isolation membrane/phagophore. GFP-LC3 dot formation is
      suppressed and endogenous LC3-I accumulates in Atg101 siRNA-treated cells,
      suggesting that Atg101 is a critical factor for autophagy. Furthermore, Atg101 is
      important for the stability and basal phosphorylation of Atg13 and ULK1. These
      data suggest that Atg101 is a novel Atg protein that functions together with ULK,
      Atg13 and FIP200.

PMID- 19597336
TI  - CD13+CD4+CD25hi regulatory T cells exhibit higher suppressive function and
      increase with tumor stage in non-small cell lung cancer patients.
AB  - Regulatory T cells (Tregs) in peripheral blood and tumor infiltrating lymphocytes
      (TILs) play crucial roles in suppressing anti-tumor immune responses in cancer
      patients, and correlate with clinical outcomes. We identified an important
      subpopulation, CD13+CD4+CD25hiTreg cells, among CD4+CD25hiTreg cells in the
      peripheral blood of non-small cell lung cancer (NSCLC) patients. Peripheral blood
      mononuclear cells (PBMCs) were isolated from patients with NSCLC (n = 72) or from
      healthy donors (n = 30). Flow cytometric analyses were performed to study the
      expression of cell-surface or intracellular markers on the CD4+CD25hiTreg cells.
      The immune suppressive function of CD13+CD4+CD25hiTreg cells was evaluated by co
      culturing with CD4+CD25-T cells that were activated by PHA. Our data showed that,
      compared with CD4+CD25(Low/-)T cells, CD13 expression was enriched on
      CD4+CD25hiTreg cells. The CD13+CD4+CD25hiTreg cells also expressed higher levels
      of Foxp3, CTLA-4, membrane-bound transforming growth factor beta1 (mTGFbeta1) and
      B7-H1, and are more suppressive to CD25 expression and proliferation of CD4+CD25
      T cells. Additionally, we showed that the expression of Foxp3, CTLA-4, B7-H1,
      mTGFbeta1 and the secretion of TGFbeta1 and IL-10 on CD13+CD4+CD25hiTreg cells
      was significantly suppressed by anti-CD13 mAb (WM15), and the ability of these
      cells to suppress CD25 expression and proliferation of CD4+CD25-T cells was
      inhibited by WM15 as well. Interestingly, the percentage of CD13+CD4+CD25hiTreg
      cells among the CD4+CD25hiTreg population increased significantly and correlated
      with pathological stage in NSCLC: healthy donor (9.84% +/- 2.23%) <stage I
      (21.64% +/- 2.78%) <stage II (31.86% +/- 3.01%) <stage III (45.64% +/- 6.12%)
      <stage IV (58.78% +/- 12.89%). Moreover, the percentage of CD13+CD4+CD25hiTreg
      cells decreased dramatically after surgical removal of tumors. CD13 is a new
      surface molecule for identifying a CD4+CD25hiTreg cell subpopulation with higher
      suppressive ability. The percentage of CD13+CD4+CD25hiTreg cells among the
      CD4+CD25hiTreg cell population correlated with the pathological stage in NSCLC
      and tumor burden. CD13 represents a potential target to suppress Treg cells in
      anti-tumor therapy.

PMID- 19597337
TI  - The COMA complex is required for Sli15/INCENP-mediated correction of defective
      kinetochore attachments.
AB  - Before anaphase, kinetochores of sister chromatid (SC) pairs must be attached to
      microtubules emanating from opposing spindle poles. The conserved Aurora B kinase
      Ipl1 and its adaptor INCENP/Sli15 correct defective attachments and promote SC bi
      orientation. Ame1 and Okp1 are essential components of the COMA sub-complex of
      the budding yeast central kinetochore, and Ame1 has been demonstrated to
      physically interact with Sli15. Here, we examine the significance of the Ame1
      Sli15 interaction in vivo. We find Sli15 localization at kinetochores is reduced
      in the absence of Ame1. We demonstrate a role for Ame1 in the correction of
      defective attachments. While overexpression of OKP1 restores kinetochore
      localization of the mutant Ame1-4 protein, Sli15 localization is not restored and
      defective attachments are not corrected. Our findings reveal a new role for the
      central kinetochore in promoting Sli15 function, and suggest functional Ame1 is
      required for the correction of defective attachments by promoting the
      localization of Sli15/INCENP at kinetochores.

PMID- 19597338
TI  - Implications of the nucleosome code in regulatory variation, adaptation and
      evolution.
AB  - Despite its importance in transcriptional regulation, only recently has
      epigenetics attracted attention in the research of genomic expression variation
      and evolution. Recent studies suggested that positioned nucleosomes in a specific
      region of the promoter are associated with regulatory variation, regardless of
      being stochastic, environmental, genetic or evolutionary. Further, this
      intrinsically variable transcriptional pattern was proposed to be hardwired in
      the underlying promoter sequences that govern nucleosome organization. It seems
      that this nucleosome code for intrinsic variation is essential in the regulatory
      control of stress response. Stochastic remodeling of cis-encoded nucleosomes
      could provide transcriptional plasticity and resilience to transient
      environmental stresses. In response to long-term environmental challenges,
      however, genetic adaptation of the nucleosome code might lead to a converged
      epigenetic state, translating short-term adaptation into evolutionary adaptation.
      This is supported by the observation that the relevant nucleosome codes in the
      genomes of yeast species reflect their phylogenetic relationships.

PMID- 19597339
TI  - Effects of cell number on teratoma formation by human embryonic stem cells.
AB  - Teratoma formation is a critical obstacle to safe clinical translation of human
      embryonic stem (ES) cell-based therapies in the future. As current methods of
      isolation are unable to yield 100% pure population of differentiated cells from a
      pluripotent donor source, potential development of these tumors is a significant
      concern. Here we used non-invasive reporter gene imaging to investigate the
      relationship between human ES cell number and teratoma formation in a xenogenic
      model of ES cell transplantation. Human ES cells (H9 line) were stably transduced
      with a double fusion (DF) reporter construct containing firefly luciferase and
      enhanced green fluorescent protein (Fluc-eGFP) driven by a human ubiquitin
      promoter. Immunodeficient mice received intramyocardial (n = 35) or skeletal
      muscle (n = 35) injection of 1 x 10(2), 1 x 10(3), 1 x 10(4), 1 x 10(5) or 1 x
      10(6) DF positive ES cells suspended in saline for myocardium and Matrigel for
      skeletal muscle. Cell survival and proliferation were monitored via
      bioluminescence imaging (BLI) for an 8 week period following transplantation.
      Mice negative for Fluc signal after 8 weeks were followed out to day 365 to
      confirm tumor absence. Significantly, in this study, a minimum of 1 x 10(5) ES
      cells in the myocardium and 1 x 10(4) cells in the skeletal muscle was observed
      to be requisite for teratoma development, suggesting that human ES cell number
      may be a critical factor in teratoma formation. Engraftment and tumor occurrence
      were also observed to be highly dependent on ES cell number. We anticipate these
      results should yield useful insights to the safe and reliable application of
      human ES cell derivatives in the clinic.

PMID- 19597340
TI  - IDO inhibits T-cell function through suppressing Vav1 expression and activation.
AB  - PURPOSE: Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme, plays
      an important role in immune escape through suppressing T-cell function. Since
      Vav1 signaling pathway regulates T cell homeostasis, this study was designed to
      test the hypothesis that IDO induces T-cell immunosuppression through inhibiting
      Vav1 signaling. RESULTS: We found that IDO produced by IDO stably expressing CHO
      cells significantly inhibited interleukin (IL)-2 expression and proliferative
      response in T cells and increased apoptosis of T cells. IDO suppressed Vav1 mRNA
      and protein production in T cells. Furthermore, IDO inhibited TCR activation
      induced Vav1 phosphorylation, which represents Vav1's activation state in T
      cells. These effects on T-cells induced by co-culture of CHO/IDO with T cells
      were attenuated by 1-MT. MATERIALS AND METHODS: Chinese hamster ovary (CHO) cells
      were stably transfected with human IDO (CHO/IDO). CD3(+) T cells were isolated
      from human peripheral blood monouclear cells. After co-culture of CHO/IDO cells
      with T cells in the presence or absence of an anti-CD3 antibody to activate T
      cell receptor (TCR) and/or 1-methyl-L-tryptophan (1-MT) to inhibit IDO activity,
      T cell proliferation and apoptosis were determined. T cell total RNA and cellular
      protein samples were isolated for detecting Vav1 gene and protein expression and
      activation state. CONCLUSIONS: The inhibitory effects of IDO on T cell immune
      responses may be through downregulation of Vav1 protein expression and
      activation. These studies provide insight into understanding the mechanisms of
      immune escape induced by IDO and therapeutic application of IDO inhibitors for
      cancer treatment.

PMID- 19597342
TI  - Divergent transcription: a new feature of active promoters.
AB  - Divergent transcription is common of many promoters in organisms as diverse as
      mammals and yeast. Many independent experiments indicate that RNA polymerase II
      is frequently initiated but paused in the sense direction downstream from the
      promoter. Similarly a second peak of transcriptionally-engaged polymerase is
      paused in the anti-sense direction upstream of the promoter. Chromatin
      modifications that are associated with active promoters reside in nucleosomes
      immediately flanking this pair of paused polymerases. The nucleosome-free region
      associated with most promoters could in part be defined by this divergent
      transcription. The potential implications of divergent transcription on gene
      regulation and possible mechanisms that give rise to this phenomenon are
      discussed.

PMID- 19597343
TI  - Functional similarities and uniqueness of p27 and p57: insight from a knock-in
      mouse model.
AB  - The cyclin-dependent kinase inhibitors (CKIs) p27 and p57 are structurally
      similar, and their biochemical and cellular functions have been thought to be
      equivalent. However, mice deficient in either p27 or p57 exhibit markedly
      different phenotypes, suggesting that the in vivo roles of these two proteins
      might differ. To address this apparent discrepancy, we have generated a knock-in
      mouse model in which the endogenous p57 gene is replaced by the p27 gene, with
      p27 thus being expressed instead of p57. This mouse model has provided evidence
      that p57 functions as a bona fide CKI in vivo and that most of its roles can be
      performed by p27. Our findings also highlight and provide insight into the
      question of what determines the distinct cellular responses to abnormal cell
      cycling induced by the loss of CKIs.

PMID- 19597341
TI  - FAS-associated factor 1 (FAF1): diverse functions and implications for
      oncogenesis.
AB  - FAS-associated factor 1, FAF1, is an evolutionarily conserved protein that has
      several protein interaction domains. Although FAF1 was initially identified as a
      member of the FAS death-inducing signaling complex, subsequent work has revealed
      that FAF1 functions in diverse biological processes. FAF1 has been shown to play
      an important role in normal development and neuronal cell survival, whereas FAF1
      downregulation may contribute to multiple aspects of tumorigenesis. In
      particular, there is compelling evidence implicating FAF1 as a tumor suppressor
      involved in the regulation of apoptosis and NFkappaB activity, as well as in
      ubiquitination and proteasomal degradation. Here, we highlight FAF1's role in
      NFkappaB signaling and postulate that this pathway has critical connotations for
      the pathogenesis and treatment of human cancers.

PMID- 19597344
TI  - Evolution, biogenesis and function of promoter-associated RNAs.
AB  - Transcription initiation is a tightly controlled process that involves chromatin
      modifications and nucleosome remodelling, transcription factor binding, and the
      assembly and recruitment of the RNA Polymerase II (RNAPII) complex. Recent
      studies have reported a diversity of long and short RNAs derived from eukaryotic
      promoters, which may be involved in transcription regulation. Here we review
      these species with particular attention to the features and biogenesis of
      transcription initiation RNAs (tiRNAs), a class of 18 nucleotide small RNA
      conserved from insects to mammals. We also report and discuss the observation
      that tiRNAs are not present in plants and are not clearly expressed in the
      nematode C. elegans. We suggest that tiRNAs may be intimately connected RNAPII
      backtracking, nucleosome marking, and gene regulation.

PMID- 19597345
TI  - Atg26-mediated pexophagy and fungal phytopathogenicity.
AB  - Colletotrichum orbiculare is a plant pathogenic fungus that causes disease on
      cucumber plants. A homologue of ATG26 (CoATG26) was identified as the gene
      involved in pathogenesis. The peroxisomes are degraded via pexophagy during
      formation of an infection structure called the appressorium of C. orbiculare. The
      Coatg26 mutant developed appressoria but exhibited a specific defect in the
      subsequent host invasion step. Importantly, the autophagic degradation of
      peroxisomes was significantly delayed in the appressoria of the Coatg26 mutant.
      Domain and localization analysis of CoAtg26 also demonstrated a strong
      correlation of functional pexophagy with pathogenicity. Furthermore, in contrast
      to the Coatg26 mutant, the Coatg8 mutant, defective in the entire autophagic
      pathway, could not form normal appressoria in the earlier steps of morphogenesis.
      These results indicate that CoAtg26-mediated pexophagy plays critical roles in
      host plant invasion.

PMID- 19597346
TI  - New perspectives on APC control of cell fate and proliferation in colorectal
      cancer.
AB  - Aberrant Wnt/beta-catenin signaling following loss of the tumor suppressor
      adenomatous polyposis coli (APC) is thought to initiate colon adenoma formation.
      Considerable evidence for this model has come from mouse models of Apc truncation
      where nuclear beta-catenin is detectable soon after loss of Apc. However,
      examination of tumors from familial adenomatous polyposis coli (FAP) patients has
      failed to confirm the presence of nuclear beta-catenin in early lesions following
      APC loss despite robust staining in later lesions. This observation presents the
      possibility that colon adenomas arise through a beta-catenin-independent function
      of APC. Additionally, there is a well established role for inflammation and
      specifically COX-2 and prostaglandin E2 in the progression of colorectal cancer.
      Here we review the current literature regarding the functions of APC in
      regulating WNT/beta-catenin signaling as well as its control of intestinal cell
      fate and differentiation. Further, we provide a brief commentary on our current
      understanding of the role that inflammation plays in colorectal tumorigenesis and
      how it fits in with APC dysfunction. Though there are currently contrasting
      models to explain colon tumorigenesis, our goal is to begin to reconcile data
      from multiple different model systems and provide a functional view into the
      initiation and progression of colon cancer.

PMID- 19597347
TI  - DNA ligase I and Nbs1 proteins associate in a complex and colocalize at
      replication factories.
AB  - DNA ligase I is the main DNA ligase activity involved in eukaryotic DNA
      replication acting in the joining of Okazaki fragments. This enzyme is also
      implicated in nucleotide excision repair and in the long-patch base excision
      repair while its role in the recombinational repair pathways is poorly
      understood. DNA ligase I is phosphorylated during cell cycle at several serine
      and threonine residues that regulate its participation in different DNA
      transactions by modulating the interaction with different protein partners. Here
      we use an antibody-based array method to identify novel DNA ligase-interacting
      partners. We show that DNA ligase I participates in several multiprotein
      complexes with proteins involved in DNA replication and repair, cell cycle
      control, and protein modification. In particular we demonstrate that DNA ligase I
      complexes with Nbs1, a core component of the MRN complex critical for detection,
      processing and repair of double-stranded DNA breaks. The analysis of epitope
      tagged DNA ligase I mutants demonstrates that the association is mediated by the
      catalytic fragment of the enzyme. DNA ligase I and Nbs1 colocalize at replication
      factories during unperturbed replication and after treatment with DNA damaging
      agents. Since MRN complex is involved in the repair of double-stranded DNA breaks
      by homologous recombination at stalled replication forks our data support the
      notion that DNA ligase I participates in homology dependent pathways that deal
      with replication-associated lesions generated when replication fork encounters
      DNA damage.

PMID- 19597348
TI  - Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell
      motility, proliferation and enhances cell sensitivity to chemotherapeutic
      reagents.
AB  - Results from tissue microarray in this study and our previous reports revealed
      that stomatin-like protein 2 (SLP-2) is notably associated with tumorigenesis and
      metastasis. Many members of stomatin family are involved in tumor as
      mitochondrial component, and recent study has revealed that SLP-2 may also
      function in mitochondria. To further investigate the function of SLP-2, we used
      siRNA target SLP-2. Data showed that knock-down of SLP-2 potently inhibited cell
      motility, proliferation and slightly altered cell cycle without any significant
      change of apoptosis. Moreover, by combined application with different
      chemotherapeutic reagents, we observed the enhancement of cell chemosensitivity
      by SLP-2 depletion. We also confirmed that, SLP-2 localizes in mitochondria,
      affects mitochondrial membrane potential (MMP) and ATP production. We conclude
      that, SLP-2 is a mitochondrial protein and therefore, functions in energy process
      by MMP maintenance, and subsequently affecting cell motility, proliferation and
      chemosensitivity.

PMID- 19597350
TI  - The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability.

PMID- 19597349
TI  - Therapy for prion diseases: Insights from the use of RNA interference.
AB  - Insights into the molecular basis and the temporal evolution of neurotoxicity in
      prion disease are increasing, and recent work in mice leads to new avenues for
      targeting treatment of these disorders. Using lentivirally mediated RNA
      interference (RNAi) against native prion protein (PrP), White et al. report the
      first therapeutic intervention that results in neuronal rescue, prevents symptoms
      and increases survival in mice with established prion disease.(1) Both the target
      and the timing of treatment here are crucial to the effectiveness of this
      strategy: the formation of the neurotoxic prion agent is prevented at a point
      when diseased neurons can still be saved from death. But the data also give new
      insights into the timing of treatment in the context of the pattern of spread of
      prion infection throughout the brain, with implications for developing the most
      effective treatments.

PMID- 19597351
TI  - Exploring Rak tyrosine kinase function in breast cancer.
AB  - Protein tyrosine kinases have been implicated in the regulation of many cellular
      events such as cellular proliferation, differentiation and development.
      Deregulation of protein tyrosine kinase activity has been shown to result in
      human cancer. The majority of the protein tyrosine kinases studied to date
      localize to the cell membrane, where they function as components of signal
      transduction pathways. However, small group of nuclear tyrosine kinases has been
      identified that includes Rak. Our recent investigations demonstrated that Rak
      functions as a potent tumor suppressor by regulating PTEN protein stability and
      function. Rak also effectively suppresses phenotypes associated with in vitro
      transformation in breast cancer cells and tumorigenicity in vivo. Moreover,
      depletion of Rak is sufficient to induce tumorigenicity in mammary epithelial
      cells. However, the mechanisms by which Rak and its substrates function in cancer
      remain largely unexplored, leaving many potential therapeutic targets yet
      undiscovered. Therefore, fully elucidating the biological functions of Rak may
      contribute to effective therapeutic approaches for Rak-defective cancers.

PMID- 19597353
TI  - Performance-based and subjective measures of functioning in middle-aged and older
      adults with bipolar disorder.
AB  - Performance-based measures may be useful in quantifying functional impairment
      associated with bipolar disorder, particularly among older adults. Among 30
      outpatients with bipolar disorder and 31 normal comparison subjects (NCs), we
      administered the UCSD Performance-Based Skills Assessment (UPSA) and 2 subjective
      measures of functioning. The UPSA simulates real-world everyday tasks, such as
      financial management. We compared UPSA scores between groups and, within the
      bipolar group, examined associations between UPSA scores and subjective
      functioning, cognitive functioning, and depressive, and manic symptoms. By large
      effect sizes, the bipolar disorder group had lower scores on the UPSA and its
      subscales compared with NCs. Within the bipolar group, UPSA scores correlated
      strongly with Quality of Well-Being Scale but not SF-36 scores, and the UPSA was
      not related to depressive or manic symptoms, but was associated with cognitive
      functioning. Given its relative independence from symptoms, the UPSA may be
      useful in gauging the effectiveness of rehabilitation for bipolar disorder.

PMID- 19597352
TI  - A role for p53 in the regulation of extracellular matrix metalloproteinase
      inducer in human cancer cells.
AB  - EMMPRIN, a transmembrane glycoprotein known to promote survival, invasion and
      metastasis of tumor cells through multiple pathways and mechanisms, has been
      found to be overexpressed in various types of cancer cells. Here we report that
      loss of the function of p53, a tumor suppressor protein that is mutated in
      approximately 50% of human cancers, contributes to the upregulation of EMMPRIN
      protein. We observed an inverse association between the activity of p53 and the
      level of EMMPRIN protein in several cancer cell lines. We further demonstrated
      that p53 is able to negatively regulate EMMPRIN protein, but downregulation of
      EMMPRIN by p53 is independent of repression of the EMMPRIN transcription.
      Furthermore, downregulation of EMMPRIN by p53 can be rescued by chloroquine, a
      lysosome inhibitor, but not by MG132, a proteasome inhibitor, suggesting an
      involvement of the lysosomal pathway in the p53-regulated degradation of EMMPRIN.
      Downregulation of EMMPRIN by p53 leads to a decrease in the activity of MMP-9 and
      an inhibition of tumor cell invasion. Our study suggests that the upregulation of
      EMMPRIN seen in many cancers can be attributed to, at least in part, the
      dysfunction of p53 and thus provides new evidence for the roles of p53 in tumor
      development and progression.

PMID- 19597355
TI  - Interpersonal and emotional experiences of social interactions in borderline
      personality disorder.
AB  - GENERAL AIM: We examined interpersonal experiences of patients with borderline
      personality disorder (BPD) using a time-contingent diary procedure to collect
      information about social interactions for 7 days. METHOD: We examined the (1)
      quantity of social interactions and (2) interpersonal and emotional experiences
      during social interactions for patients with BPD (BPD; N = 42) compared with
      those with another personality disorder (OPD; N = 46) and those without
      significant personality pathology (NOPD; N = 23). RESULTS: Results suggested that
      BPD patients have fewer social contacts compared with those in the NOPD group.
      Additionally, the BPD patients characterized their social interactions as more
      disagreeable, ambivalent, angry, empty, and sad compared with the OPD and NOPD
      groups. BPD patients reported experiencing more anxiety and less positive affect
      compared with the NOPD but not the OPD group. CONCLUSION: These findings
      highlight aspects of day-to-day interpersonal functioning that are specific to
      BPD.

PMID- 19597354
TI  - Independent associations between personality traits and clinical characteristics
      of depression.
AB  - Few studies have examined age of onset and chronicity of depression in the same
      subject sample. The present study sought to determine whether personality traits
      related to early onset depression were different from those related to chronic
      depression. We tested the associations between personality self-reports and
      clinical characteristics of depression by conducting multiple and logistic
      regression analyses to determine whether personality uniquely predicted clinical
      characteristics and whether clinical characteristics uniquely predicted
      personality, after adjusting for depression severity. We also analyzed data at 6
      month follow-up to determine whether age of onset and chronicity maintained their
      associations with personality. The study found that low levels of positive
      personality traits had unique associations with chronicity of depression, whereas
      elevated levels of negative personality traits had unique associations with an
      earlier onset of depression. Furthermore, associations were generally maintained
      over time, suggesting that associations between personality and these depression
      subtypes are stable.

PMID- 19597357
TI  - Prevalence, correlates, and predictors of depersonalization experiences in the
      German general population.
AB  - The survey aimed to investigate the prevalence of depersonalization (DP)
      experiences, its sociodemographic characteristics and its associations with
      medical conditions, illness behavior, and potential etiologic factors. A
      representative face-to-face household survey was conducted. The sample consists
      of n = 1,287 participants aged 14 to 90 years. Sociodemographic variables,
      medical conditions, current mental disorders, health care utilization, and
      childhood adversities were assessed. A total of 1.9% participants scored in the
      range of clinically significant DP (DP-C) and 9.7% reported at least some
      impairment through DP (DP-I). DP-C/DP-I were strongly associated with depression
      and anxiety. After adjustment for depression and anxiety, DP-C and DP-I were
      independently associated with hypertension, diabetes mellitus, chronic pulmonary
      disease, severe pain, and childhood adversities. We conclude that DP is common,
      it can not be reduced to a negligible variant of depression or anxiety and that
      more awareness about DP with respect to detection and research is urgently
      required.

PMID- 19597356
TI  - Alexithymia, absorption, and cognitive failures in depersonalization disorder: a
      comparison to posttraumatic stress disorder and healthy volunteers.
AB  - Alexithymia, absorption, and cognitive failures are traits that have been
      implicated in dissociative psychopathology. Forty-six participants with
      depersonalization disorder (DPD), 21 with posttraumatic stress disorder, and 35
      healthy controls completed measures of dissociation, alexithymia, absorption,
      cognitive failures, and childhood trauma. The DPD and posttraumatic stress
      disorder groups had significantly and comparably elevated absorption and
      cognitive failures scores. Only the DPD group had significantly elevated
      alexithymia scores, specifically in "difficulty identifying feelings." Regression
      analyses revealed that "alexithymia-difficulty identifying feelings" was
      predictive of both DPD diagnosis and depersonalization scores. In contrast,
      amnesia scores were predicted by childhood trauma and absorption. In conclusion,
      the link between depersonalization and alexithymia appeared to be specific rather
      than broadly related to early trauma or to trauma-spectrum psychopathology.

PMID- 19597358
TI  - Does the form or the amount of exposure make a difference in the cognitive
      behavioral therapy treatment of social phobia?
AB  - Exposure is considered to be an essential ingredient of cognitive-behavioral
      therapy treatment of social phobia and of most anxiety disorders. To assess the
      impact of the amount of exposure on outcome, 30 social phobic patients were
      randomly allocated to 1 of 2 group treatments of 8 weekly sessions: Self-Focused
      Exposure Therapy which is based essentially on prolonged exposure to public
      speaking combined with positive feedback or a more standard cognitive and
      behavioral method encompassing psychoeducation, cognitive work, working through
      exposure hierarchies of feared situations for exposure within and outside the
      group. The results show that the 2 methods led to significant and equivalent
      symptomatic improvements which were maintained at 1-year follow-up. There was a
      more rapid and initially more pronounced decrease in negative cognitions with the
      Self-Focused Exposure Therapy, which included no formal cognitive work, than with
      the more standard approach in which approximately a third of the content was
      cognitive. In contrast, decrease in social avoidance was more persistent with
      standard cognitive-behavior therapy which involved less exposure. The results
      indicate that positive cognitive change can be achieved more rapidly with non
      cognitive methods while avoidance decreases more reliably with a standard
      approach rather than an approach with an exclusive focus on exposure.

PMID- 19597359
TI  - Temperament and character dimensions in patients with schizophrenia, relatives,
      and controls.
AB  - Studies of patients with schizophrenia or schizophrenia spectrum disorders and
      general population control groups consistently show differences regarding
      personality dimensions. However, the profile of personality dimensions in first
      degree relatives of those patients is not well understood. We used Temperament
      and Character Inventory to explore personality dimensions in 61 clinically stable
      patients with schizophrenia or schizophrenia spectrum disorders, 59 of their
      first-degree relatives, and 64 healthy controls. Patients scored significantly
      higher than controls in harm avoidance and self-transcendence and lower in self
      directedness and cooperativeness. First-degree relatives showed a tendency to
      lower novelty seeking and self-transcendence than controls. Interpretations of
      these findings include the possibility that lower novelty seeking and lower self
      transcendence provide a protective influence in the relatives. Further studies
      are needed to go into this issue in greater depth.

PMID- 19597360
TI  - Awareness of stigma among persons with schizophrenia: marking the contexts of
      lived experience.
AB  - This article investigates the subjective experience of stigma attached to
      schizophrenia-related disorders. We examine data from anthropological interviews
      from a community sample of 90 out-patients residing in a metropolitan area of the
      United States. Patients were under treatment with atypical antipsychotic
      medication, and their symptoms were for the most part relatively well controlled.
      Overall, 96% of participants reported an awareness of stigma that permeated their
      daily life. Based on an understanding of stigma as a product of interpersonal,
      reciprocal social processes, we identify 6 types of social relations and 5
      identity domains in which social stigma is routinely encountered by participants.
      We describe the experience of stigma in each of these 11 subcategories, and
      suggest that taken together they constitute a framework of social and personal
      factors involved in the struggle to recover from psychotic illness. Among types
      of social relations, anonymous social interactions most commonly generated an
      awareness of stigma. Among identity domains, being a person who regularly takes
      medication was most commonly associated with an awareness of stigma. The finding
      that multiple forms of stigma are encountered irrespective of substantial
      symptomatic, functional, and subjectively perceived improvement creates a complex
      situation of stigma despite recovery.

PMID- 19597361
TI  - Diagnosis of schizophrenia in latino populations: a comparison of direct
      interview and consensus based multi-source methods.
AB  - We determined the rates of agreement between diagnoses, using the Diagnostic
      Interview for Genetic Studies (DIGS) and diagnoses arrived at, using additional
      sources of information, to establish whether there are differences in agreement
      between direct interview diagnoses at US and non-US sites in comparison best
      estimate consensus process and to identify diagnoses that could increase
      diagnostic error when only the DIGS is used. DIGS diagnoses were compared with
      consensus diagnoses that used the same DIGS interview, plus Family Interview for
      Genetic Studies (FIGS) and review of medical records in 342 psychotic subjects.
      We found similar numbers of subjects diagnosed with schizophrenia (225 by direct
      interview, and 232 by consensus process). The majority of those "misdiagnosed" by
      direct interview had mood disorder by the consensus. Over 10% of the total
      subjects diagnosed by direct interview as not meeting criteria for schizophrenia
      had schizophrenia by consensus. There were no statistically significant
      differences between countries (US vs. non-US sites) in the agreement rate between
      direct interview diagnosis and consensus diagnosis. In conclusion, a final best
      estimate process is essential to make diagnostic distinctions and to reduce
      diagnostic misclassifications for both research studies and in clinical practice.

PMID- 19597362
TI  - Shame, guilt, and posttraumatic stress disorder in adult survivors of childhood
      sexual abuse at risk for human immunodeficiency virus: outcomes of a randomized
      clinical trial of group psychotherapy treatment.
AB  - This study evaluated the effectiveness of group psychotherapy in reducing levels
      of shame and guilt in adult survivors of childhood sexual abuse at risk for HIV,
      and whether such reductions would mediate the effects of treatment on
      posttraumatic stress disorder (PTSD) symptoms. One hundred sixty-six women were
      randomized into 3 conditions: a trauma-focused group, a present-focused group,
      and a waitlist group. Women received 6 months of treatment and were assessed at
      pretreatment (T1), immediately posttreatment (T2), and 6 months posttreatment
      (T3). Both treatment conditions resulted in reduced shame and guilt. The
      treatment effect on PTSD symptoms was mediated by changes in shame, but it was
      not associated with changes in guilt. These findings suggest that, when treating
      childhood sexual abuse survivors' PTSD, it is important to address the negative
      self-appraisals, such as shame, that commonly accompany such symptoms.

PMID- 19597363
TI  - Psychological and relationship distress among partners of civilian PTSD patients.
AB  - Significant others of individuals with posttraumatic stress disorder (PTSD) may
      experience both intrapersonal and interpersonal distress as caregivers. The aim
      of the present study is 3-fold: (1) to examine symptoms of psychological and
      relationship distress (anxiety, depression, and dyadic adjustment) among partners
      of civilian patients with PTSD, (2) to investigate the links between partners'
      distress and PTSD patients' symptoms (severity; intrusion, avoidance, and arousal
      subscales), and (3) to explore the perception of mental and physical health,
      types of trauma and compare partners and PTSD patients' measures. Fifty-seven
      PTSD patients and their partners filled out 4 questionnaires: Marital Adjustment
      Test, Beck Anxiety Inventory, Beck Depression Inventory-II, and Medical Outcome
      Survey-Short Form-12. Results showed that only a minority of partners presented
      clinical levels of depression (16.7%), anxiety (14.8%), and relationship distress
      (37%). Pearson correlations analyses revealed an absence of statistically
      significant relationship between partners' distress and PTSD patients' symptoms.
      In conclusion, although our study is not a direct validation of the secondary
      traumatic stress model, our findings fail to provide strong support to the
      secondary traumatic stress hypothesis among partners of civilian PTSD patients.

PMID- 19597364
TI  - Defense style changes with the addition of psychodynamic group therapy to
      clonazepam in social anxiety disorder.
AB  - Psychodynamic Group Therapy (PGT) and clonazepam are strategies to reduce
      symptoms of generalized social anxiety disorder (GSAD). The addition of PGT might
      lead to changes in defense styles. The objective of this study is to examine
      changes in defense styles when comparing clonazepam to psychodynamic group
      therapy plus clonazepam in GSAD during 12 weeks. Fifty-seven patients that met
      DSM-IV criteria for GSAD participated. social anxiety disorder symptoms were
      evaluated with the Liebowitz Social Anxiety Scale, and defense styles with the
      Defense Style Questionnaire. All defense styles changed overtime for both groups,
      especially mature defense style, which increased independently of the treatment
      allocation group. Regression analyses found that overtime there was a reduction
      in neurotic defenses in the combined group, whereas there was an increase in the
      clonazepam group. Neurotic defense style can change toward greater adaptiveness
      with the addition of PGT to clonazepam in GSAD, even in 12 weeks.

PMID- 19597366
TI  - Neurohormonal regulation of cardiac ion channels in chronic heart failure.
AB  - Alteration of neurohormonal homeostasis is a hallmark of the pathophysiology of
      chronic heart failure (CHF). In particular, overactivation of the renin
      angiotensin-aldosterone system and the sympathetic catecholaminergic system is
      consistently observed. Chronic overactivation of these hormonal pathways leads to
      a detrimental arrhythmogenic remodeling of cardiac tissue due to dysregulation of
      cardiac ion channels. Sudden cardiac death resulting from ventricular arrhythmias
      is a major cause of mortality in patients with CHF. All the drug classes known to
      reduce mortality in patients with CHF are neurohormonal blockers. The aim of this
      review was to provide an overview of how cardiac ion channels are regulated by
      hormones known to play a central role in the pathogenesis of CHF.

PMID- 19597365
TI  - Gender differences, anger expression, and cardiovascular risk.
AB  - Research has established the influence of serum cholesterol and anger management
      style as cardiovascular risk factors. However, mixed and sometimes contradictory
      results have created uncertainty with respect to contributions of anger. Some
      incongruities may be accounted for on the basis of gender differences since a
      number of studies have employed male samples rather than female samples or mixed
      samples. The present study examined both gender and anger management style in
      relation to cardiovascular risk. One hundred three (72 men and 31 women) midlevel
      executives completed questionnaires and a blood draw during a week long,
      succession training program within a large international organization. Gender,
      anger expression, and anger expressed outward were significant predictors for
      levels of high-density lipids, low-density lipids/very low-density lipids, and
      triglycerides, and cardiovascular risk ratios. Results replicate and extend
      previous research. Anger held inward and anger control were significant for men
      but not women, contrary to earlier gender-specific findings.

PMID- 19597367
TI  - Channeling a new focus for heart failure: insights into ion channels.

PMID- 19597368
TI  - Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in
      hypertriglyceridemic subjects.
AB  - BACKGROUND/RATIONALE: Treatment of severe hypertriglyceridemia is indicated to
      reduce the risk of pancreatitis in patients with triglyceride (TG) levels > or
      =500 mg/dL. Hypertriglyceridemia is also a risk factor for atherosclerotic
      coronary heart disease. Prescription omega-3 fatty acids (P-OM3) and fenofibrate
      (FENO) are among the most effective lipid-altering agents that reduce TG levels.
      Given that some patients may not achieve optimal TG levels with a single agent,
      we hypothesized that concomitant use of P-OM3 or addition of P-OM3 to FENO would
      result in a TG reduction greater than that with FENO alone. METHODS: This
      randomized, 8-week, double-blind, placebo-controlled study was designed to
      compare the safety and efficacy of P-OM3 4 g QD plus concomitant FENO 130 mg with
      FENO 130 mg QD plus placebo in subjects with very high TG levels (> or =500
      mg/dL). Subjects who completed the double-blind study were given the option to
      continue into an open-label, 8-week extension study, wherein they all received P
      OM3 4 g plus FENO 130 mg QD. On completion of the first extension study, subjects
      were eligible to continue into an open-label 24-month extension of the treatment
      with P-OM3 4 g plus FENO 130 mg QD. RESULTS: Concomitant P-OM3 + FENO (n = 81)
      and FENO monotherapy (n = 82) reduced median TG values from 649.5 to 267.5 mg/dL
      (60.8%) and from 669.3 to 310 mg/dL (53.8%), respectively (P = 0.059). When
      subjects who had received 8 weeks of stable FENO monotherapy were given P-OM3
      during the 8-week, open-label extension study (n = 58), TG levels were reduced
      17.5% (P = 0.003) over the course of the extension. The second extension phase
      was terminated early (n = 93)-not because of a safety signal but because of the
      lack of a substantial incremental change in the primary endpoint lipid values
      above that reached in either the original study or the first extension in
      subjects receiving the combination of fenofibrate and P-OM3. CONCLUSIONS: Both
      FENO monotherapy and P-OM3 + FENO significantly reduced TGs in subjects with very
      high TGs, with a trend to greater reduction in the P-OM3 + FENO group. The
      addition of P-OM3 to stable FENO therapy in the same subjects in an open-label
      extension study resulted in a statistically significant reduction in TG levels.
      Subjects who received P-OM3 + FENO for 16 weeks and subjects in which P-OM3 was
      added to FENO monotherapy during the open-label phase of the study did not differ
      in their final lipid responses. In the second open-label extension, within the
      combined group taking P-OM3 and FENO, analysis of change from the second
      extension baseline to end of treatment revealed no clinically important change.

PMID- 19597369
TI  - Short- and long-term cardioprotective effect of darbepoetin-alpha: role of Bcl-2
      family proteins.
AB  - The purpose of this study was to assess the short- and long-term cardioprotective
      effects of darbepoetin-alpha (DA) in a rat myocardial ischemia and reperfusion
      model and to investigate the signaling pathway through which DA limits
      cardiomyocytes apoptosis. Rats were subjected to 40 minutes of coronary artery
      ligation followed by 72 hours or 4 weeks reperfusion and received either DA (3 or
      30 microg/kg, DA3 and D30 groups) or vehicle (control) prior to ischemia. In the
      DA groups reperfused for 72 hours, left ventricular shortening fraction and left
      ventricular ejection fraction were higher than that in the control rats (P <
      0.05), in agreement with a smaller left ventricular (LV) infarct size. DA
      treatment activated the JAK2/Akt signaling pathway, lowered cleaved caspase-3,
      and increased both phosphorylated-Bad and phosphorylated-GSK-3beta proteins. This
      was consistent with the decrease of reactive oxygen species production and the
      lowered binding of Bad to Bcl-xL and Bcl-2 in a DA30 group of rats. Similarly, in
      the DA-4-week group, LV function was greater compared to the control. Histology
      alterations implicated lower LV cardiac fibrosis and greater capillary density;
      furthermore, both Bcl-xL and Bcl-2 were upregulated. In conclusion, DA afforded
      short- and long-term cardioprotective effects. Antiapoptotic effects, through the
      activation of Akt that regulates the Bcl-2 family proteins and activates GSK
      3beta, are central in the DA cardioprotective mechanism.

PMID- 19597370
TI  - CARDIAC role of the mitochondrial Ca2+ transporters in the high-[K+](o)
      cardioprotection of rat hearts under ischemia and reperfusion: a mechano
      energetic study.
AB  - The role of mitochondrial transporters in the cardioprotection of rat hearts
      exposed to high [K+]-low [Ca2+]-cardioplegia (CPG) and ischemia and reperfusion
      (I/R) was studied through the mechano-energetic consequences of target drugs. The
      total heat rate (Ht) and the left intraventricular pressure (LVP) were
      simultaneously measured in isolated perfused hearts (30 degrees C and 1 Hz)
      inside a flow-calorimeter during 45 minutes of no-flow I and 45 minutes of R.
      After stabilization (C) they were pretreated with CPG and 100 microM 5
      hydroxidecanoate (5HD, selective mKATP blocker) without and with 10 or 30 microM
      clonazepam (Clzp, mNCX inhibitor), 30 microM diazoxide (Dzx, selective mKATP
      opener), 1 microM Ru360 (selective Ca-uniporter blocker), and 0.2 microM
      cyclosporine-A, (mPTP inhibitor, before I and during R). Before I, 5
      hydroxydecanoate in CPG increased the resting heat rate (17.83 +/- 3.55 mW/g)
      without changing the stunning. Clzp 30 microM + CPG + 5-hydroxydecanoate reduced
      the postischemic P with diastolic contracture and high Ht. Dzx protected C-hearts
      from stunning but increased it in CPG hearts with low economy (P/Ht) as well as
      Ru360. Cyclosporine-A did not modify the stunning of C or CPG ischemic hearts,
      suggesting that the mPTP was not opened. CONCLUSIONS: Mitochondria have a precise
      role for determining cardioprotection or stunning in high-K+ cardioplegic rat
      hearts under I/R. Known protective drugs, such as Dzx and Ru360, which reduce the
      mitochondrial Ca2+-uptake, increased the stunning of CPG-rat hearts and reduced
      muscle economy, whereas 5-hydroxydecanoate and Clzp together increased the
      stunning by inducing mitochondrial Ca2+ overload.

PMID- 19597372
TI  - Relationship between quality of care and functional decline in hospitalized
      vulnerable elders.
AB  - BACKGROUND: Although process of care is a valuable dimension of quality, process
      of-care-based quality indicators (POC-QIs) are ideally associated with meaningful
      patient outcomes. The relationship between POC-QIs for hospitalized older
      patients and functional decline, a relevant outcome for older patients, is
      unknown. OBJECTIVE: To assess the relationship between POC-QIs for hospitalized
      elders and functional decline. RESEARCH DESIGN: Observational cohort study.
      SUBJECTS: Hospitalized vulnerable elder patients age 65 or older admitted to a
      general medicine inpatient service from June 1, 2004 to June 1, 2007. MEASURES:
      POC-QIs received by hospitalized patients (measured by Assessing Care of
      Vulnerable Elders QIs) and functional decline (increased activities of daily
      living impairments postdischarge). RESULTS: For 898 vulnerable elder patients,
      mean adherence to 6 universally applied quality indicators was 57.8%. After
      adjustment for factors likely associated with functional decline (comorbidity,
      vulnerability, baseline functional limitation, number of POC-QIs triggered,
      length of stay, code status, and interaction between frailty and QI adherence),
      there was no association higher quality of care (using the composite score) and
      increased risk of functional decline. Patients who received a mobility plan were
      1.48 (95% CI: 1.07-2.05; P = 0.017) times more likely to suffer functional
      decline after discharge. Patients who received an assessment of nutritional
      status had a lower odds of suffering functional decline after discharge (OR:
      0.37, [95% CI: 0.21-0.64; P < 0.001]). CONCLUSIONS: Hospitalized vulnerable
      elders who receive higher quality of care, as measured by Assessing Care of
      Vulnerable Elders QIs, are not less likely to suffer decline after discharge.

PMID- 19597371
TI  - Mechanosensitive channels in striated muscle and the cardiovascular system: not
      quite a stretch anymore.
AB  - Stretch-activated or mechanosensitive channels transduce mechanical forces into
      ion fluxes across the cell membrane. These channels have been implicated in
      several aspects of cardiovascular physiology including regulation of blood
      pressure, vasoreactivity, and cardiac arrhythmias, as well as the adverse
      remodeling associated with cardiac hypertrophy and heart failure. This review
      discusses mechanosensitive channels in skeletal muscle and the cardiovascular
      system and their role in disease pathogenesis. We describe the regulation of
      gating of mechanosensitive channels including direct mechanisms and indirect
      activation by signaling pathways, as well as the influence on activation of these
      channels by the underlying cytoskeleton and scaffolding proteins. We then focus
      on the role of transient receptor potential channels, several of which have been
      implicated as mechanosensitive channels, in the pathogenesis of adverse cardiac
      remodeling and as potential therapeutic targets in the treatment of heart
      failure.

PMID- 19597373
TI  - External validity of the cardiovascular health study: a comparison with the
      Medicare population.
AB  - BACKGROUND: The Cardiovascular Health Study (CHS), a population-based prospective
      cohort study, has been used to identify major risk factors associated with
      cardiovascular disease and stroke in the elderly. OBJECTIVE: To assess the
      external validity of the CHS. RESEARCH DESIGN: Comparison of the CHS cohort to a
      national cohort of Medicare beneficiaries and to Medicare beneficiaries residing
      in the CHS geographic regions. SUBJECTS: CHS participants and a 5% sample of
      Medicare beneficiaries. MEASURES: Demographic and administrative characteristics,
      comorbid conditions, resource use, and mortality. RESULTS: Compared with both
      Medicare cohorts, the CHS cohort was older and included more men and African
      American participants. CHS participants were more likely to be enrolled in
      Medicare managed care than beneficiaries in the national Medicare cohort.
      Compared with the Medicare cohorts, mortality in the CHS was more than 40% lower
      at 1 year, approximately 25% lower at 5 years, and approximately 15% lower at 10
      years. There were minimal differences in comorbid conditions and health care
      resource use. CONCLUSION: The CHS cohort is comparable with the Medicare
      population, particularly with regard to comorbid conditions and resource use, but
      had lower mortality. The difference in mortality may reflect the CHS recruitment
      strategy or volunteer bias. These findings suggest it may not be appropriate to
      project absolute rates of disease and outcomes based on CHS data to the entire
      Medicare population. However, there is no reason to expect that the relative
      risks associated with physiologic processes identified by CHS data would differ
      for nonparticipants.

PMID- 19597374
TI  - Calcineurin contributes to spatial memory impairment induced by rapid eye
      movement sleep deprivation.
AB  - Recent evidence suggests that rapid eye movement (REM) sleep deprivation (REMSD)
      causes learning and memory deficits. However, the mechanism of REMSD-induced
      memory impairment remains unclear. Calcineurin (CaN) is involved in synaptic
      plasticity and is known as a negative constraint on learning and memory. Here we
      report that 72 h REMSD by the modified multiple platform method in rats resulted
      in spatial memory impairment in the Morris water maze and elevated hippocampal
      cytosolic CaN activity, both of which were reversed after 18 h sleep recovery.
      CaN expression in the whole-tissue homogenate of the hippocampus was not altered
      by REMSD. The results suggest that elevated hippocampal CaN activity is involved
      in REMSD-induced spatial memory impairment.

PMID- 19597375
TI  - Duration-sensitive neurons in the auditory cortex.
AB  - The aim of this study was to determine whether there is a difference in the
      neural encoding of tones and complex sounds. Obligatory cortical auditory evoked
      potentials were obtained from normal hearing adults using tones and complex
      sounds with two stimulus durations and two inter-stimulus intervals. The response
      was smaller in amplitude for all of the long duration stimuli when using a short
      inter-stimulus interval. The difference in amplitude between the short and long
      duration tones disappeared when using the longer inter-stimulus interval but
      persisted for the complex sounds. The results provide evidence for duration
      sensitive neurons in the auditory cortex as well as evidence for differences in
      the neural encoding of tones and complex sounds.

PMID- 19597376
TI  - Center-surround organization of face-space: evidence from contrast-based face
      priming.
AB  - 'Face-space' is an abstract concept of the multidimensional representation of
      faces. Faces of similar appearance are closer in face-space than dissimilar
      faces; however, it is not clear how representations interact. Examining contrast
      thresholds for facial recognition, we show that a 200 ms preview of a face
      facilitates recognition of the same face, but inhibits recognition of other
      faces, more so for the same ethnic group than for a different ethnic group. This
      suggests a center-surround organization in which facial representations close to
      the priming stimulus are more suppressed than those that are distant.

PMID- 19597377
TI  - Unions warn against back door revolution.

PMID- 19597378
TI  - An overview of suprapubic catheter care in community practice.
AB  - This paper gives a broad overview of suprapubic catheterization. Community nurses
      can often feel they lack experience with suprapubic catheter general care and
      routine changes. This paper sets out the advantages and disadvantages of
      suprapubic catheters, the procedure for routine change and the golden rules for
      general care. The paper contains an introduction on trouble shooting.

PMID- 19597379
TI  - Managing type 2 diabetes: new policy and interventions.
AB  - This paper presents a critical discussion of the recent developments in diabetes
      services and concurrent patient care, which have a significant impact on the way
      that community nurses provide care to people with diabetes. The current
      prevalence and rising incidence of type 2 diabetes is discussed, mentioning how
      this trend will impact on community nursing practice. New interventions and
      management guidelines are presented and discussed, with a focus on patient
      centred care as the main driver for these changes. New pharmacological
      interventions (Byetta) and biochemical outcome measures are discussed which will
      have an impact on patient care, delivered by nurses working in the community.

PMID- 19597380
TI  - The role of the community nurse in hepatitis C diagnosis and treatment.
AB  - Hepatitis C is a common cause of liver disease and many infected individuals
      remain undiagnosed. Patients may be asymptomatic or have non-specific symptoms,
      and community nurses can help to identify those at risk and arrange testing.
      Community nurses can also encourage and support infected individuals to attend
      specialist hospital clinics for assessment and treatment by giving clear and
      accurate information about infection and therapy, including common side-effects.
      Treatment lasts for 6-12 months and patients require regular monitoring with good
      support. This paper provides an overview of the diagnosis and management of
      hepatitis C and aims to educate community nurses about this viral infection.

PMID- 19597381
TI  - Partnership working with independent providers.
AB  - The Department of Health in England want to see NHS commissioners and providers
      capitalize upon the expertise of the independent sector for the benefit of NHS
      patients. In preparing for the future what does the sector have to offer NHS
      nurses and how will this benefit patient care? This paper examines the role of
      independent providers and the way they are helping NHS commissioners and
      providers to break new ground in delivering more accessible and convenient care
      for NHS patients at home.

PMID- 19597382
TI  - Transition for adolescents with long-term conditions: event to process.
AB  - This paper maps out the evidence relating to quality and user experience of
      transition services for young people with long-term conditions. The review
      identified that good quality transition was universally seen as a process as
      opposed to a single event, supported by effective interagency communication and
      coordination, with the young person occupying a central place in the decision
      making process. Conversely, poor communication and an absence of a designated
      professional to support the transition were barriers to an effective process.
      Gaps in the evidence base were most notable when concerned with the relationship
      between general practice, secondary care and social care. Overall, greater shared
      learning of the generic components of an effective transition process needs to
      occur across long-term conditions.

PMID- 19597384
TI  - Understanding the Safeguarding Vulnerable Groups Act 2006.
AB  - The Safeguarding Vulnerable Groups Act 2006 was enacted as a result of the
      Government adopting the recommendations of the Bichard Inquiry (2004), that
      looked into the circumstances surrounding the death of two children in Soham in
      2002. The 2006 Act provides a new vetting and barring scheme to replace the
      existing arrangements for safeguarding children and vulnerable adults from harm,
      or the risk of harm, by employees and volunteers whose work gives them
      significant access to these vulnerable groups. The Act extends statutory vetting
      and barring schemes to the health service as well as the social care sector. It
      is therefore important that district nurses are aware of the provisions of the
      Act and the timetable for implementation. This will enable them to better
      understand their legal duties, in order to protect themselves from liability and
      to protect their patients from abuse.

PMID- 19597383
TI  - Raising awareness of elder abuse in the community practice setting.
AB  - In 2000 the Department of Health published No Secrets: Guidance on developing and
      implementing multi-agency policies and procedures to protect vulnerable adults
      from abuse. This has laid the foundation for multi-agency policy development for
      the prevention of abuse of vulnerable adults at the national and local level.
      Recognition and appropriate action by community practitioners is essential to
      safeguard the welfare of older people. This paper aims to provide an overview of
      the key policy and research initiatives surrounding elder abuse, and to provide
      clear guidance in terms of identifying and reporting possible cases of abuse.

PMID- 19597385
TI  - The future role of the nurse.

PMID- 19597386
TI  - What is the optimal surgical therapeutic target in functional ischemic mitral
      regurgitation: annulus, chord, ventricle, or papillary muscle?

PMID- 19597388
TI  - A unique milieu for perioperative care of adult congenital heart disease patients
      at a single institution.
AB  - PURPOSE: Adult patients with congenital heart disease presenting for
      cardiothoracic operation pose special demands for the arrangement of their
      perioperative care. This study describes the distinctive perioperative setup for
      adult congenital heart patients. MATERIALS AND METHODS: A retrospective review of
      48 adult congenital heart disease cases that received operative intervention from
      July 2000 to October 2005. Operative procedures and postoperative care were all
      exercised in the same unit by the same staff handling adult and pediatric
      cardiothoracic surgery cases. RESULTS: Forty-two patients underwent definitive
      biventricular repair, and the remainder were subjected to palliative procedures.
      There were 2 cases of operative mortality: 1 patient died as a result of
      arrhythmia after Glenn procedure, and 1 died as a result of multiorgan failure
      secondary to sepsis after ventricular septal defect repair. Complications that
      prolonged intensive care stay for more than 72 hours were extracorporeal support
      for systemic right ventricular dysfunction (n = 1); reoperation for ventricular
      septal patch endocarditis after ventricular septal defect repair (n = 1);
      respiratory failure (n = 4); renal failure (n = 3); sepsis (n = 2); junctional
      tachycardia (n = 1); pulmonary hypertension (n = 2); and reperfusion injury of
      the lung (n = 2). Patients subjected to the Fontan operation had a longer
      hospital stay (mean = 33 days) as a result of pleural effusions. Forty-six
      patients were discharged home. CONCLUSION: This distinctive environment allows
      our group to provide the appropriate care for our adult congenital heart disease
      patients in a well-integrated discipline. The frequent clinical exposure to both
      adult and pediatric cardiothoracic procedures has helped in facilitating the
      provision of optimum care to the patients with adult congenital heart disease.

PMID- 19597387
TI  - Individualized adjuvant chemotherapy for surgically resected lung cancer and the
      roles of biomarkers.
AB  - Several prospective randomized trials for patients with completely resected
      stages II and IIIA nonsmall cell lung cancer have confirmed a survival benefit
      with cisplatin-based adjuvant chemotherapy. The Lung Adjuvant Cisplatin
      Evaluation, which is based on pooled analyses of five randomized trials, has
      demonstrated a 4.2% absolute survival benefit at 5 years. The stage is the
      benchmark standard used to decide the indication for adjuvant chemotherapy;
      however, it is important to identify and select the patients who would benefit
      from adjuvant chemotherapy and to choose the optimal regimen for each case. The
      translational research was performed using specimens obtained in the above
      adjuvant trials also to obtain information concerning biomarkers and subsets of
      patients who would benefit from adjuvant chemotherapy. The extent to which
      individualized treatment of lung cancer can be provided, especially adjuvant
      chemotherapy, is discussed in this manuscript.

PMID- 19597389
TI  - Individualized off-pump all internal thoracic artery revascularization.
AB  - OBJECTIVE: We developed an individualized off-pump approach in an all internal
      thoracic artery (AITA) composite graft revascularization (AITACR) program to
      minimize postoperative neurological complications and to obtain the best long
      term results possible. Early results of the individualized approach are reported.
      PATIENTS AND METHODS: The operative method (on-pump or off-pump) was determined
      based on institutional selection criteria. Early neurological outcomes were
      evaluated in 157 men and 42 women; the mean age was 67.3 +/- 9.3 years. RESULTS:
      Fifty-nine underwent off-pump procedures and 140 on-pump. The off-pump patients
      were older than the on-pump patients. The prevalence of diabetes mellitus,
      history of previous cerebral infarction, and atherosclerotic disease in the
      ascending aorta was more frequent in the off-pump group than in the on-pump
      group. The total number of distal anastomoses was 3.2 +/- 0.9 per patient. There
      was no operative mortality. Three patients (1 in the off-pump group and 2 in the
      on-pump group) had postoperative cerebral infarctions possibly related to
      postoperative atrial fibrillation. CONCLUSIONS: When patients were allocated to
      the on-pump group or the off-pump group based on our criteria, excellent results
      were achieved with acceptable morbidity. An individualized off-pump approach in
      an AITACR program appears reasonable and safe with excellent early neurological
      outcomes.

PMID- 19597390
TI  - Mitral valve repair for 52 patients with severe left ventricular dysfunction.
AB  - BACKGROUND: Mitral valve (MV) repair is considered to provide more favorable
      results than MV replacement. MV repair in a patient with severe left ventricular
      (LV) dysfunction could be associated with higher early and late mortality.
      Surgical indication of MV repair for those with low LV ejection fraction (LVEF)
      is still controversial. PATIENTS AND METHODS: Fifty-two patients with severe
      mitral regurgitation (MR) and severe LV dysfunction (EF < 35%) underwent MV
      repair with or without concomitant procedure. The commonest etiology of MV
      disease was ischemic origin (78.8%), which underwent annuloplasty alone. Their
      pre- and perioperative parameters were analyzed to identify the risk factor for
      mortality. The follow-up data of hospital survivors were collected. RESULTS:
      Early mortality was 9.6%. The cause of all deaths was low cardiac output
      syndrome. Actuarial survival was 81.6% at 2 years and 76.5% at 5 years.
      Multivariate analyses revealed chronic hemodialysis and EF < 25% to be the risk
      factors for early and late mortality. Among hospital survivors, significant
      improvement of LVEF (29.9 to 37.4%) and reduction of LV diastolic dimension (62.8
      to 57.9 mm) were observed during follow-up. CONCLUSION: MV repair is effective to
      improve long-term prognosis of high-risk patients of severe MR with severe LV
      dysfunction.

PMID- 19597391
TI  - Left ventricular reconstruction with or without mitral annuloplasty.
AB  - OBJECTIVES: The aim of this study was to review characteristics of patients
      undergoing left ventricular reconstruction (LVR) with or without mitral
      annuloplasty (MAP) for postinfarction ventricular remodeling. PATIENTS AND
      METHODS: Forty-seven patients were divided into two groups: LVR (LVR group, n =
      22) and LVR with MAP (LVRM group, n = 25). Echocardiographic parameters including
      left ventricular (LV) dimensions, LV end-diastolic and end-systolic volume
      indexes, and LV ejection fraction (LVEF) at immediate and midterm postoperative
      stages were evaluated. The perioperative contributing factors to all deaths and
      death from congestive heart failure (CHF) were analyzed in all 47 patients.
      RESULTS: Patients in the LVRM group had greater preoperative LV dimension and
      volume, and significantly lower LVEF, with notably frequent use of intra-aortic
      balloon pumping. All postoperative deaths occurred within 1 year from surgery.
      The LV end-diastolic volume > 110 ml/m2 and creatinine > 1.2 mg/dl were
      significant preoperative contributing factors to all deaths, and the latter was
      to CHF deaths. CONCLUSIONS: The coexistence of ischemic mitral regurgitation with
      LV dilatation required more aggressive surgical approaches for the patients with
      more impaired LV function. More intensive postoperative management is required
      for patients with enlarged hearts and renal dysfunctions.

PMID- 19597392
TI  - Chronic expanding hematoma with bronchopleural fistula and empyema space.
AB  - Chronic expanding hematoma of the thorax is not typically accompanied by a
      bronchopleural fistula or purulent lesion. We report an extremely rare case of
      chronic expanding hematoma with a bronchopleural fistula and empyema space in a
      66-year-old man with a history of tuberculous pleurisy admitted because of fever
      and bloody sputa. Computed tomography and a magnetic resonance imaging revealed a
      huge mass and an air space in the right thorax. A fiber-optic bronchoscope
      examination showed hemorrhagic effusion from the apical bronchus of the right
      lower lobe. First, open-window thoracostomy was undertaken to control the septic
      state and to prevent aspiration of infected pleural fluid. At operation, air
      leakage was found at the most superior portion in the rear of the thoracic
      empyema space; this was thought to be from the bronchopleural fistula.
      Enterococcus casseliflavus was detected in cultures for bacteria of the effusion
      from the empyema space. After an improvement of his general condition, a radical
      operation, including the complete extirpation of the hematoma and intrathoracic
      muscle transposition using the latissimus dorsi muscle, was successfully
      performed.

PMID- 19597393
TI  - Squamous cell carcinoma presenting as a solitary growing cyst in lung: a
      diagnostic pitfall in daily clinical practice.
AB  - Gradually growing cystic lesion of the lung is commonly encountered in daily
      clinical practice. Thin-walled cavitary lung cancer is a rare entity; however, it
      could be a pitfall in the diagnosis of such radiographically benign-looking
      lesions, especially without an obvious solid, nodular, or tumorous appearance in
      the lesion. We herein report a rare case of lung cancer successfully treated by
      surgical resection that appeared as a gradually growing cystic lesion mimicking
      benign emphysematous disease, with a review of the literature. A 68-year-old man
      with a 24-year history of hypothyroidism presented with an abnormal cystic shadow
      in the left lung on routine chest X-ray. Twelve months later, occasional bloody
      sputa had started and was gradually getting worse. The patient was then referred
      to our department for surgical intervention. He received clarithromycin by daily
      oral administration, and the bloody sputa soon disappeared. However, a malignancy
      was still suspected because the wall was slightly thickened unevenly in
      comparison with the previous chest X-ray and computed tomography findings. Thus
      we performed a left lower lobectomy followed by mediastinal dissection because a
      squamous cell carcinoma was diagnosed by intraoperative frozen section. The
      patient postoperatively received 4 courses of paclitaxel-carboplatin therapy.
      Twelve months after surgery, he survives without recurrence.

PMID- 19597394
TI  - A case of recurrence and rapid growth of pleural solitary fibrous tumor 8 years
      after initial surgery.
AB  - A 69-year-old woman underwent resection of a solitary fibrous tumor (SFT) of the
      left pleura in April 1997 and of locally recurrent SFT in the left thoracic
      cavity in September 2003. A postoperative follow-up chest CT scan in March 2005
      revealed pleural thickening at two sites of the left thoracic cavity. A further
      chest CT scan performed in September of the same year showed the enlarging
      tendency of the lesions, suggesting SFT recurrence, for which surgery was
      performed in January 2006. The two resected tumors were benign SFT, and were
      diagnosed as locally recurrent SFT in the left thoracic cavity. It has been
      reported that despite its benign histopathology, pleural SFT recurs more than
      once after surgery, and the interval between recurrences tends to shorten from
      the second recurrence. In this patient, the tumor recurred twice and showed a
      rapidly enlarging tendency at the time of the second recurrence, suggesting the
      need for careful follow-up at short intervals.

PMID- 19597395
TI  - Surgical resection and reconstruction for primary malignant sternal tumor.
AB  - We report a very rare and successful surgery for primary malignant tumor of the
      sternum. A 73-year-old male, previously healthy, was admitted to our hospital
      because a chest computed tomography scan detected an abnormal shadow that
      suggested a sternal tumor destroying part of the sternum body. Aspiration needle
      biopsy demonstrated a primary sternal chondrosarcoma measuring 3 x 4 cm in
      diameter. The sternum below the second intercostal space was resected along with
      a 1-cm width of cartilage below the third rib on each side. Sternal
      reconstruction was performed with Composix mesh, titanium mesh, and Marlex mesh,
      using a right pectoralis major muscle flap translation. The patient was extubated
      just after surgery, and the postoperative course was uneventful. This procedure
      may be useful for repairing the detect after wide sternotomy.

PMID- 19597396
TI  - Primary lung cancer with growth into the lumen of the pulmonary artery.
AB  - We describe a 68-year-old man with primary lung cancer, misdiagnosed as pulmonary
      thromboembolism, with growth into the lumen of the pulmonary artery (PA). The
      tumor was surgically unresectable because of difficulty with the bronchoplasty;
      however, it was progressing rapidly and obstructing the main PA. We urgently
      performed a partial resection of this tumor and occluded the left PA ostium with
      autologous pericardium to avoid spread into the main PA.

PMID- 19597397
TI  - Pulmonary metastasis from renal cell carcinoma 17 years after nephrectomy: report
      of two cases.
AB  - We herein report two cases of pulmonary metastasis from renal cell carcinoma with
      17-year disease-free intervals. Despite long disease-free intervals, their
      clinical course after pulmonary resection was different. An 82-year-old man (case
      1) and a 73-year-old man (case 2), with histories of having undergone left
      nephrectomy for clear-cell-type renal cell carcinoma 17 years ago, were found to
      have right pulmonary nodules, which were detected incidentally by chest
      roentgenograms. A chest computed tomography revealed the presence of nodules in
      the right lung. They underwent surgical pulmonary resection 17 years after
      nephrectomy. These tumors were diagnosed as metastatic renal cell carcinoma.
      Currently, the case 1 patient is doing well with no signs of recurrence 42 months
      after pulmonary metastasectomy; however, the case 2 patient was found to have
      multiple tumor recurrences 11 months after metastasectomy. Their clinical courses
      indicate that a longer disease-free interval does not always imply a favorable
      prognosis.

PMID- 19597398
TI  - Large subpectoral hematoma: possible complication of sternotomy post-cardiac
      surgery.
AB  - A 62-year-old female patient developed a significantly enlarged left breast 6
      hours after sternotomy for a coronary artery bypass graft operation. This was the
      result of subpectoral bleeding caused by a sternal wire.

PMID- 19597399
TI  - Surgical repair for a coronary-pulmonary artery fistula with a saccular aneurysm
      of the coronary artery.
AB  - The patient, a 69-year-old woman, had been diagnosed with a heart murmur. A chest
      X-ray at a local clinic had shown an abnormal shadow. Since CT revealed a 3-cm
      diameter mass close to the pulmonary artery, we performed a coronary angiography
      and diagnosed her as having a coronary artery aneurysm associated with a coronary
      pulmonary artery fistula. We incised the aneurysm under cardiac arrest, the wall
      of which had three openings that were suture closed from the inside and outside.
      The coronary-pulmonary artery fistula was suture closed. A postoperative
      angiography confirmed the disappearance of the coronary artery aneurysm and the
      abnormal blood vessels. The patient had an uneventful postoperative course and
      was discharged on postoperative day 15. We report a rare case of coronary
      pulmonary artery fistula with a coronary artery aneurysm for which surgery was
      followed by an uneventful postoperative course.

PMID- 19597400
TI  - Surgical treatment of coronary artery aneurysm with coronary artery fistula.
AB  - Coronary artery aneurysm (CAA) is an uncommon disease with an incidence of 1%-5%
      in evaluated patients. Atherosclerosis is its most common etiology in adults,
      occurring in 50% of cases. Also, CAA is associated with predisposing factors such
      as Kawasaki disease, stent-angioplasty, and notably, coronary artery fistula.
      Most CAAs are asymptomatic but occasionally lead to life-threatening conditions,
      such as rupture, infection, and myocardial ischemia. Thus caution is urged for
      cardiac surgeons. We here report on seven surgical cases of CAA with coronary
      artery fistula in our institute, focusing on their surgical treatment.

PMID- 19597401
TI  - Unruptured, isolated giant aneurysm of the sinus of valsalva resulting from
      medial mucoid degeneration.
AB  - We report a quite rare case of unruptured, isolated giant aneurysm of the sinus
      of Valsalva resulting from medial mucoid degeneration in a young adult woman. A
      29-year-old Japanese female diagnosed as having an aneurysm of the sinus of
      Valsalva and severe aortic regurgitation with no clinical findings of Marfan's
      syndrome or Ehlers-Danlos syndrome. A modified Bentall's operation was performed
      successfully, and she was discharged with no complications. A pathological
      examination revealed marked medial mucoid degeneration of the aneurismal wall. In
      the literature, most giant aneurysms resulting from mucoid degeneration were
      found in African young adult females. In this case, there was much mucoid
      degeneration in the media with no focal destruction of elastic fibers, which was
      distinct from cystic medial necrosis in Marfan's syndrome. A careful follow-up
      will be required to detect any other aneurysmal formation in the future.

PMID- 19597402
TI  - Endotracheal surgery for leiomyoma of the trachea.
AB  - A 61-year-old male was found to have a tracheal tumor, which was noted at the
      time of screening by a chest X-ray study. The tumor arose from the membranous
      portion 4 cm above the carina and was proven by biopsy to be a leiomyoma. Because
      the disease is a benign tumor, all methods for resection, including bronchoscopic
      techniques, were thus considered. We performed an endotracheal operation via a
      window made by an incision of the cartilagenous portion, and removed the tumor
      through an anterior approach. This type of endotracheal operation is one of the
      surgical procedures for the removal of benign tracheal tumors.

PMID- 19597403
TI  - New concepts and new roles for vascular medicine/angiology and vascular surgery.
      A developing role for vascular specialists: from the hospital, to the community,
      to the enviroment. The example of environmental estrogens.

PMID- 19597404
TI  - Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy
      individuals and in hypertensive patients.
AB  - This study was conducted with the aim of showing the effects of Pycnogenol on
      controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7
      days starting 2 days prior to the flight was used. The study was divided into two
      separate parts. In study 1 the most common complaints of patients with jet-lag
      were evaluated with a rating scale consisting in of a scoring system. In study 2
      a brain CT scan was performed after the flight in order to assess minimal brain
      edema (MBE) in association with typical signs and symptoms, observed in previous
      published flight studies. Study one included 38 subjects treated with Pycnogenol
      and 30 controls. The symptomatic jet-lag related total score was significantly
      lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average
      duration of any jet lag symptom following the flight was significantly reduced
      from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the
      Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol
      and 31 controls. The main observation was the brain CT scan performed within 28
      hours after the end of the flight. The difference between the Pycnogenol and the
      control groups was statistically significant (P<0.05) for all items assessed
      including the cerebral edema score obtained by CT scan. The short-term memory was
      significantly altered in the control group and associated to edema and swelling
      of the lower limbs. The score (and the level of edema) was comparatively higher
      in a subgroup of hypertensive subjects in the control group. Minor alterations of
      cardiac function were observed in association with de-stabilisation of blood
      pressure. Fatigue was also significantly higher in the control group in
      comparison with the Pycnogenol group. A number of spontaneously reported symptoms
      was also scored and there was a statistically significant difference (P<0.05)
      between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to
      control jet-lag and minimal brain edema.

PMID- 19597406
TI  - Fingerprints and cardiovascular risk. The San Valentino fingerprint vascular
      screening project (SanVal/FP).
AB  - Fingerprints (FP), characteristic of humans, are impressions due to skin marks
      (ridges) on fingertips. Ridges are present on fingers/hands forming curved lines
      of different sizes/patterns. The point where a line stops or splits is defined
      typica' (their number/amount constitute identification patterns). FP are
      permanent and unique. This study compared FP patterns with cardiovascular risk
      factors: 7 main types of FP were used: 1. Arch: lines form waves from one site to
      the other side. 2. Tentarch: like arches but with a rising stick in the middle.
      3. Loop: lines coming from one site returning in the middle to the same site. 4.
      Double loop: like loops but with two loops inside: one standing, one hanging. 5.
      Pocked loop: like the loop but with a small circle in the turning point. 6.
      Whorl: lines make circles. 7. Mixed figure: composed of different figures. There
      are two kinds of real typica: A. Ending line; B. Splitting lines (bifurcations).
      Several combinations may result. Ultrasound evaluation of carotid/femoral
      arteries in asymptomatic subjects. Arteries were evaluated with high-resolution
      ultrasound at the bifurcations. Four classes were defined: 1: normal intima-media
      (IMT) complex; 2: IMT thickening; 3: non-stenosing plaques (<50% stenosis); 4:
      stenosing plaque (>50%). Subjects in classes 1, 2, 3 were included into the
      analysis made comparing FP patterns and ultrasound. RESULTS: For each FP pattern:
      A. the main proportion of subjects with cardiovacular risk factors (91%) had
      arches (41.2%) and loops (either single, 38.2% or double 11.7% for a total of
      49.9%). B. The remaining classes were statistically less important. C. The number
      of ridges per square mm was comparable in all pattern classes. D. The analysis of
      typica and other ridges characteristics requires a more elaborated system. Future
      research must define simple, low cost screening methods for preselection of
      subjects at higher cardiovascular risk or for exclusion of low risk subjects. The
      evaluation of fingerprint pattern may be useful to define risk groups.

PMID- 19597405
TI  - [NPT (near patient test) in the pharmacy: document and practice guidelines 2008].
AB  - NPT tests in the pharmacy. Blood testing can be made with NPT (near patient
      testing) directly in the pharmacy. Most tests can be made with a single drop of
      blood (i.e. from a finger) and results are comparable with results from blood
      test obtained with standard vein blood samples. NPT is basically used for: 1 -
      evaluating the risk of a disease. 2 evaluating or confirming the presence of a
      disease. 3 to manage and monitor treatments. The social role of the pharmacy in
      NPT (particularly in cardiovascular screening) is very important as the pharmacy
      is an institution with capillary diffusion in the territory. The pharmacy often
      constitutes an important, first-level consultancy point for the population,
      particularly where health institutions are far away (small villages) or not
      easily accessible. Rules for NPT. Guidelines for NPT testing in the pharmacy have
      been proposed and discussed in a consensus meeting (Spoleto, 2007). NPT
      guidelines suggest operating management and technical procedures and indicate
      prospective lines of action defining new roles for the pharmacy. Coagulation
      tests can be now made in the pharmacy at a very low cost and with an efficacy
      comparable to blood tests obtained with a vein sample. Results can be read in
      seconds. This test is also available for personal use and home testing. NPT: The
      Clinical Study. The evaluation of the results of a clinical study (patients with
      venous thrombosis/pulmonary embolisation, patients with fibrillation and patients
      with artificial cardiac valves) indicates that costing is very favourable for NPT
      which may reduce costs and improve management of many clinical conditions and
      their monitoring. Training and control systems help NPT testing to be reliable
      and useful to screen and manage most clinical and risk conditions. The clinical
      study also shows the positive correlation between NPT tests and standard' tests.
      In conclusion NPT tests are now very reliable and cost-effective and can be used
      for screening, diagnosis and to monitor treatments.

PMID- 19597408
TI  - Spontaneous recanalization of occluded internal carotid artery after minor
      stroke. The role of surgical treatment.
AB  - Late spontaneous recanalization of internal carotid artery is a very rare event.
      We describe three cases which came to our observation in which the occlusion was
      demonstrated both by angiography and Doppler ultrasound. Two of them had surgical
      treatment and the histological exam of the plaque showed multiple recanalization
      foci. Our experience confirmed the possibility of a successful surgical treatment
      that offers a good patency in the short and medium term.

PMID- 19597407
TI  - Carotid endarterectomy: comparing anesthesia in awakened and intubated patients
      with general anesthesia.
AB  - AIM: The purpose of this study was to determine utility and efficacy of
      anesthesia with remifentanil in awakened and intubated patients in comparison
      with general anesthesia and routine shunting. METHODS: Hundred patients were
      randomized for general anesthesia (group A) or anesthesia with remifentanil
      (group B). The two groups were compared in terms of postoperative outcome,
      neurological complications, arterial pressure during intervention and in during
      the following 36 hours. Group B patients answered a proposed questionnaire about
      intraoperative and postoperative degree of comfort, fear, pain and discomfort for
      the orotracheal tube. RESULTS: The two groups differed significantly only for age
      (group B>A); 10% of patients was not considered fit for the anesthesia with
      remifentanil (initial experience only). The two groups did not differ in terms of
      central neurologic complications (0%), general complications or technical
      problems in terms of intra-operative arterial pressure problems (the anesthesia
      with remifentanil caused less hypertensive problems (P>0,19) and (not technique
      dependent) peripheral neurologic deficits. All patients accepted the method and
      did not report fear or discomfort. Only 3 patients (6.6%) described light pain
      during the intervention. In 2 cases (4.4%) the surgeon complained about the
      restlessness of the patient; this did not cause a change in procedure.
      CONCLUSIONS: General anesthesia with remifentanil produces an association between
      the advantage of locoregional anesthesia and those of general anesthesia,
      probably lowering the risk for the patients.

PMID- 19597409
TI  - Treatment of ankle sprain in patients with vascular diseases of the lower limbs.
AB  - Patients (with venous or arterial disease) are particularly affected by even
      minor sprains as edema, swelling are more disabling and cause a more severe
      clinical picture. In such vulnerable population, it is imperative to rehabilitate
      the patient in shortest possible time to regain the functionality of the injured
      joint and thus assure ambulation. The aim of the present study was to compare the
      efficacy of locally applied and orally administered ketoprofen in a group of 41
      patients with vascular diseases of lower limbs with accidental grade I ankle
      sprain. Forty one patients were included in this study and divided into in three
      treatment groups: ketoprofen 10% spray gel* (360 mg/die), oral ketoprofen
      (tablets, 25 mg t.i.d. and control group (no pharmacological treatment). The
      duration of treatment was one week. The three groups of patients were comparable
      for age and sex distribution and for the clinical characteristics at inclusion.
      After seven days of treatment all patients experienced reduction of symptoms
      (pain at rest and on active movement, swelling) which was significant only in
      patients treated by topical, local application of ketoprofen. The effects of oral
      treatment were not significantly different from those observed in untreated
      controls. The minimal effort treadmill testing showed significant increase in
      pain-free walking distance in patients who applied the medication locally in
      comparison to the other groups. The tolerability of locally applied ketoprofen
      was good and no side effects were noted. The observed clinical outcomes of the
      patients included in this small, pilot study indicated that locally applied
      ketoprofen 10% spray gel is effective in relieving the pain and other symptoms of
      ankle sprain in vascular patients.

PMID- 19597410
TI  - Management of uncomplicated ankle sprains with topical or oral ketoprofen
      treatment. A registry study.
AB  - Ankle sprains mainly caused by accidents or strenuous sport activities can often
      be quite painful and impair motility. If not treated immediately and correctly,
      sprains may lead to severe complications. The aim of the present study was to
      compare the efficacy and safety of topically applied ketoprofen versus orally
      administered ketoprofen in 20 patients with grade I ankle sprain and 34 patients
      with grade II sprain. The patients were divide into in two treatment groups and
      received either topically applied ketoprofen treatment (ketoprofen 10% spray-gel;
      Prontoflex; 360 mg/die) or orally administered ketoprofen treatment (ketoprofen
      tablets; 3x50 mg/die). Treatment duration was one week. After 3 and 7 days of
      treatment, reduction of spontaneous pain and pain on active movement in the
      Prontoflex group was significantly bigger greater in the oral treatment group,
      irrespective of sprain severity. Regarding secondary parameters as mobility
      impairment and ankle swelling topically applied ketoprofen treatment turned out
      to be significantly superior to orally administered ketoprofen treatment.
      Additionally, Prontoflex was well tolerated, whereas ketoprofen tablets caused
      gastrointestinal side effects in some patients. The good efficacy in pain
      reduction and absence of side effects in the present study distinguished the
      topically applied ketoprofen as a favorable treatment for patients with
      accidental or sport soft tissue injuries.

PMID- 19597411
TI  - Deep vein thrombosis: a mininvasive locoregional thrombolytic treatment.
AB  - AIM: Locoregional thrombolytic therapy has emerged in the last years as the
      treatment of choise for iliofemoral deep vein thrombosis, preserving the
      structural and functional integrity of vein walls. We studied the efficacy and
      complication rates of direct regional thrombolytic therapy in acute venous
      thrombosis of lower extremities. METHODS: Between January 2002 and March 2007, 8
      selected patients with acute extensive and symptomatic iliofemoral or femoral
      popliteal venous thrombosis were treated with flow-direct regional thrombolytic
      therapy. We used a direct regional infusion of urokinase into the deep venous
      system ( 100.000 U al presentation, then 75.000 U/ h) from an ipsilateral dorsal
      foot vein . Simultaneously the superficial venous system was collapsed with
      elastic limb compression while administering subtherapeutic heparin doses of 300
      400 U/h. All patients underwent routine venous duplex imaging at day 1, 2, 30 and
      after 3, 6 and 12 months. Data including clinical conditions and laboratory
      values (fibrinogen, hematocrit, haemoglobin, platlets and prothrombin time) were
      obtained throughout the infusion time. Results. Procedural success was achieved
      in all patients (100%). Complete recanalization, patency and continence of venous
      system documented at the echocolorDoppler control, were obtained in 48 hours,
      with symptom remission. Mean infusion time was 37.5 hours (28-48 hours). Neither
      major bleeding complications nor pulmonary embolisms occurred during the
      treatment. At day 30 venous patency and incontinence and long-term symptom
      resolution were achieved in all patients, as well as at 3, 6 and 12 months.
      CONCLUSIONS: Loco-regional thrombolytic therapy is safe and effective in selected
      patients and may become a well-founded alternative in the treatment of acute deep
      vein thrombosis of lower extremities and in the prevenction of its complications
      .

PMID- 19597412
TI  - Use of polyglucosamine and physical activity to reduce body weight and
      dyslipidemia in moderately overweight subjects.
AB  - AIM: A low molecular weight chitosan (polyglucosamine, PG) was studied in
      overweight hyperlipemic patients under physical training. A double blind study
      was conducted in two groups of 30 patients (M/F; from 25 to 59 years). METHODS:
      Tablets containing PG (2 g/day) or placebo were given for a 4-month period during
      a physical training (+8 MET-hours/week). Anthropometric measures, caloric intake,
      blood pressure, LDL and HDL cholesterol, blood glucose and triacylglycerol were
      measured before and after the treatment. The groups were similar for the caloric
      intake and expenditure and ended up with positive results in most of the
      parameters examined. RESULTS: In PG group compared to placebo a more significant
      (P<0.05, t test) reduction was found for body weight (respectively 6.9+/-1.87 vs
      3.0+/-1.61 kg), waist circumference (7.3+/-2.49 vs 3.1+/-4.21 cm), LDL
      cholesterol (44+/-14.7 vs 12.5+/-12.6 mg/dL), triacylglycerol (52+/-29.3 vs 39+/
      15.2 mg/dL); HDL increase was also higher (6+/-3.6 vs and 3+/-4.2 mg/dL). At
      baseline metabolic syndrome (MS) according to ATP III was present in 15 and 14
      patients respectively in the group PG and placebo. CONCLUSIONS: Unexpectedly, at
      the end of the treatment MS was reduced in 12 cases of the PG group and in 3
      cases only of the placebo group (P<0.05). Results indicate that PG may improve
      the effect of the physical training in moderately overweight patients with
      dyslipidemia and may be of some help in the treatment of MS.

PMID- 19597413
TI  - LINFAVENIX: improvement of signs and symptoms of chronic venous insufficiency and
      microangiopathy.
AB  - The aim of this independent study was to demonstrate the rapidity of the efficacy
      of an oral venotropic compound (Linfavenix, including natural elements) in
      patients with chronic venous insufficiency (CVI). Two groups of patients with
      chronic venous insufficiency (CVI) ankle swelling) were treated with Linfavenix
      or with below-knee elastic compression. The average ambulatory venous pressure
      (AVP) at inclusion (both groups)was 56.2 (range 48-55) with a refilling time (RT)
      shorter than 10 seconds. These parameters indicated a severe level of venous
      hypertension. There were no significant differences in AVP and RT between the two
      groups. The two groups of subjects with CVI were comparable; in the Linfavenix
      group there were 14 patients (age 44.5; sd 4; range 34-55; 7 females); in the
      elastic compression group there were 12 patients (45.4;5; range 36-56; 7
      females). The clinical picture and microcirculatory parameters at inclusion were
      comparable. RF was comparable at inclusion in the two groups. At two weeks, the
      differences in RF (between goups) were not significant (the flux decreased in
      both groups, indicating improvement) while at 4 weeks the difference was larger
      (but non significant between the two groups) with a significant decrease in RF in
      the Linfavenix group. The RAS was also comparable at inclusion. Both groups had a
      significant decrease at 2 and 4 weeks. The decrease produced by Linfavenix after
      4 weeks in RF was larger and significant (p<0.05) in comparison with the elastic
      compression group. Also the differences observed in ASLS were significant in both
      groups with an important, significant difference in favour of Linfavenix at 4
      weeks (op<0.05) visibile as edema reduction. The decrease in edema was relevant
      in both groups at 2 (p<0.05) and 4 weeks (p<0.05) with a minimal but significant
      difference (p<0.05) between the Linfavenix and the elastic compression group.
      These variations in microcirculatory parameters indicate that the treatment with
      Linfavenix is, in its microcirculatory efficacy, at least comparable than elastic
      compression with is considered a standard therapeutic option in these patients. A
      significant level of improvement was reached with Linfavenix, in most patients
      (10/14) at 2 weeks for RF, at 7 days for the RAS and also at 2 weeks in almost
      all patients (13/14) considering ASLS and edema. No side effects due to treatment
      were observed. Compliance and tolerability were very good (no patient had to stop
      treatment; there were no drop-outs). In conclusion venous microangiopathy and
      edema were improved by the treatment with Linfavenix (better in comparison with
      compression) in a few days.

PMID- 19597414
TI  - An in vitro skin irritation test (SIT) using the EpiDerm reconstructed human
      epidermal (RHE) model.
AB  - The EpiDerm Skin Irritation test (EpiDerm SIT) was developed and validated for in
      vitro skin irritation testing of chemicals, including cosmetic and pharmaceutical
      ingredients. The EpiDerm SIT utilizes the 3D in vitro reconstructed human
      epidermal (RHE) model EpiDerm. The procedure described in this protocol allows
      for discrimination between irritants of GHS category 2 and non-irritants. The
      test is performed over the course of a 4 day time period, consisting of pre
      incubation, 60 minute exposure, 42 hour post-incubation and MTT viability assay.
      After tissue receipt and overnight pre-incubation (Day 0), tissues are topically
      exposed to the test chemicals (Day 1), which can be liquid, semisolid, solid or
      waxy. Three tissues are used for each test chemical, as well as for the positive
      control (5% aq. SDS solution), and a negative control (DPBS). Chemical exposure
      lasts for 60 minutes, 35 min of which the tissues are kept in an incubator at 37
      degrees C. The test substances are then removed from the tissue surface by an
      extensive washing procedure. The tissue inserts are blotted and transferred to
      fresh medium. After a 24 hr incubation period (Day 2), the medium is exchanged.
      The medium can be saved for further analysis of cytokines or other endpoints of
      interest. After the medium exchange, tissues are incubated for an additional 18
      hours. At the end of the entire 42 h post-incubation (day 3), the tissues are
      transferred into yellow MTT solution and incubated for 3 hours. The resultant
      purple-blue formazan salt, formed mainly by mitochondrial metabolism, is
      extracted for 2 hours using isopropanol. The optical density of the extracted
      formazan is determined using a spectrophotometer. A chemical is classified as an
      irritant if the tissue viability relative to the negative control treated tissues
      is reduced below 50%. This procedure can be used as full replacement of the in
      vivo rabbit skin irritation test for hazard identification and labeling of
      chemicals in line with EU regulations.

PMID- 19597415
TI  - Novel mechanism of rapamycin in GVHD: increase in interstitial regulatory T
      cells.
AB  - Rapamycin (RAPA) is an immunosuppressive drug that prevents and treats graft
      versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT).
      One possible mechanism for its efficacy is induction of tolerance, through
      increased number or enhanced survival of regulatory T cells. In our experiments,
      B10.D2 BM and splenocytes were injected into lethally irradiated BALB/cJ
      recipients. The mice received i.p. injections of either RAPA or vehicle control
      on days 1-28. There was a significant survival advantage in RAPA-treated mice.
      Evaluation of the skin biopsies showed a dense cellular infiltrate in RAPA
      treated mice. Further characterization of these cells revealed a higher
      percentage of regulatory T cells characterized by FoxP3-positive cells in high
      dose RAPA-treated mice as compared with controls on day 30. This effect appears
      to be dose dependent. When peripheral blood analysis for FoxP3-positive cells was
      performed, there was no significant difference observed in the RAPA-treated mice
      as compared with control mice. These data show a novel mechanism of rapamycin in
      GVHD, accumulation of regulatory T cells in the GVHD target tissue: the skin.

PMID- 19597416
TI  - Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma:
      retrospective analysis of the experience of the Fukuoka BMT group.
AB  - Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis
      after conventional chemotherapy compared with aggressive B-cell lymphoma. To
      elucidate the role of high-dose chemotherapy (HDCT) with auto-SCT, we
      retrospectively analyzed the outcomes of 39 patients with PTCL who received HDCT
      and auto-SCT between 1990 and 2005. Eleven patients were histologically typed as
      angioimmunoblastic, nine as anaplastic large-cell lymphoma, seven as natural
      killer/T-cell lymphoma and twelve as PTCL unspecified. Clinical conditions at
      transplantation were complete response (CR) in 27 patients and non-CR in 12
      patients. Thirty-two patients received a pre-transplant conditioning regimen
      (MCEC) comprising ranimustine, carboplatin, etoposide and CY, and seven did other
      TBI-based regimens. Rapid engraftment was obtained in all cases, and transplant
      related death was not seen. An estimated 5-year OS was 62.1% with a median follow
      up of 78 months. The 5-year OS was significantly higher in patients transplanted
      during complete response than in those during other disease status (71.4% vs
      27.3%, P=0.046). HDCT supported by auto-SCT may therefore be effective as
      consolidation in CR for PTCL treatment.

PMID- 19597417
TI  - Barriers to mental health service use among hematopoietic SCT survivors.
AB  - This study examined barriers to mental health service use and the demographic,
      medical and psychosocial correlates of these barriers among hematopoietic SCT
      (HSCT) survivors. A sample of 253 HSCT survivors who were 1 to 3 years
      posttransplant completed measures of demographic, physical, psychological and
      social characteristics as well as a newly modified measure of barriers to mental
      health service use. Only 50% of distressed HSCT survivors had received mental
      health services. An exploratory factor analysis of the barriers to mental health
      service use scale yielded four factors: scheduling barriers, knowledge barriers,
      emotional barriers and illness-related barriers. Patients with higher social
      constraints (perceived problems discussing the illness experience with
      significant others) reported higher levels of all four types of barriers. General
      distress and transplant-related posttraumatic stress symptoms were positively
      associated with emotional, knowledge and illness-related barriers to mental
      health service use, whereas physical and functional well-being were inversely
      associated with these barriers. Having more knowledge barriers and more emotional
      barriers predicted a lower likelihood of receiving mental health services, as did
      lower levels of education and general distress. Results suggest that a
      significant number of HSCT survivors may benefit from education about mental
      health services that is tailored to individual barriers.

PMID- 19597418
TI  - A controlled randomized study examining the effects of exercise therapy on
      patients undergoing haematopoietic stem cell transplantation.
AB  - A haematopoietic SCT (HSCT) can cause severe side effects, which may have a
      profound impact on a patient's life both physically and psychologically. Some
      studies have shown that physical activity has positive effects for inpatients
      after an HSCT. Therefore, the question arises whether a controlled exercise
      programme right from the beginning of the conditioning phase could help
      contribute to a patient's physical and psychological recovery. To evaluate the
      different effects of specific, moderate physical activities on the physical and
      psychological condition of HSCT patients we performed a controlled randomized
      study with 64 inpatients undergoing an allogeneic or autologous HSCT. The
      patients were randomly assigned to two groups. Although the training group took
      part in a specific programme of exercise therapy twice a day throughout the
      entire hospitalization phase, patients in the control group were offered the
      hospital's standard mobilization programme. The results of this study showed
      significant differences in favour of the training group regarding strength,
      endurance, lung function and quality of life. However, further studies are needed
      to confirm these results.

PMID- 19597419
TI  - Severe pulmonary toxoplasmosis after allo-SCT in two patients: from Toxoplasma
      genotyping to clinical management.

PMID- 19597421
TI  - Hematopoietic stem cell transplantation for pediatric autoimmune disease: where
      we stand and where we need to go.
AB  - In children, autoimmune diseases and their therapies cause significant morbidity,
      especially in those with severe or refractory disease. The constant development
      of new immunosuppressants and targeted biological therapies leads to a unique
      'moving target' with regard to the gold standard of treatment for these patients.
      However, incidental findings of cure after hematopoietic stem cell transplant
      (HSCT) in patients with concomitant benign or malignant hematologic disorders and
      autoimmune disease raise the question of whether HSCT can be used as upfront
      therapy for patients with severe autoimmune diseases. Animal data have been
      helpful in investigating both the efficacy of this modality and the mechanisms
      underlying cure. The potential for a therapeutic 'graft vs autoimmunity' (GVA)
      effect with an allogeneic approach highlights the already acknowledged need for
      clinical trials of allogeneic vs autologous transplant in these diseases where an
      autologous transplant would be the 'intuitive' albeit potentially erroneous
      choice. We critically review the data generated in the field thus far, and
      emphasize the need for an organized, interdisciplinary approach to conduct
      prospective clinical trials to answer these and other questions and advance the
      field.

PMID- 19597420
TI  - Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized
      evaluation of early vs late administration of recombinant human G-CSF.
AB  - The optimal timing for recombinant human (rh)G-CSF administration after
      chemotherapy for PBSC mobilization has not yet been determined. In this study, we
      compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late),
      in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC
      mobilization with CE (CY 4 g/m(2) on day 1 and etoposide 200 mg/m(2) on days 1
      3). The rhG-CSF dose was 10 microg/kg/day for all patients. Both groups were
      comparable in terms of sex, age and number of previously given different
      chemotherapy regimens. Duration of neutropenia, CD34(+) cell count on the first
      day of apheresis and numbers of aphereses were not statistically different
      between the two arms. However, the number of doses of rhG-CSF up to the first
      cycle of apheresis procedures was significantly lower in the late group than in
      the early group (P=0.005). The median number of total CD34(+) cells collected was
      10.54 x 10(6)/kg (range 0.11-37.27) in the early group and 10.81 x 10(6)/kg
      (range 0.17-49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC
      mobilization after late use of rhG-CSF is an effective approach and therefore, in
      routine clinical practice, late rhG-CSF may be used for PBSC collections after
      chemotherapy-based mobilization regimens in this cost-conscious era.

PMID- 19597423
TI  - Pituitary apoplexy complicating auto-SCT.

PMID- 19597422
TI  - Mobilization of peripheral blood stem cells for autologous transplant in non
      Hodgkin's lymphoma and multiple myeloma patients by plerixafor and G-CSF and
      detection of tumor cell mobilization by PCR in multiple myeloma patients.
AB  - This report describes the first investigational use of plerixafor in Europe and
      the determination of tumor cell mobilization by polymerase chain-reaction after
      plerixafor treatment in a subset of patients with multiple myeloma (MM). Thirty
      five patients (31 MM and 4 NHL) received granulocyte colony-stimulating factor (G
      CSF) (10 microg/kg) each morning for 4 days. Starting the evening of Day 4,
      patients recieved plerixafor 0.24 mg/kg. Apheresis was initiated 10-11 h later,
      in the morning of Day 5. This regimen of G-CSF treatment each morning before
      apheresis and plerixafor treatment in the evening was repeated for up to 5
      consecutive days. Mobilization with plerixafor and G-CSF resulted in a median 2.6
      fold increase in peripheral blood (PB) CD34+ cell count compared with before
      plerixafor treatment. All patients collected > or =2 x 10(6) CD34+ cells/kg and
      32 of 35 patients collected > or =5 x 10(6) CD34+ cells/kg. After plerixafor
      treatment, 3 of 7 patients had a small increase and 4 of 7 patients had a small
      decrease in PB tumor cells. No G-CSF was given post transplant. The median number
      of days to polymorphonuclear leukocyte and platelet engraftment was 14.0 and
      11.0, respectively. There were no reports of graft failure. Plerixafor was
      generally well tolerated. Mobilization of PB CD34+ cells was consistent with
      previous clinical trials. The addition of plerixafor did not significantly
      increase the relative number of PB MM tumor cells.

PMID- 19597424
TI  - CR with lenalidomide in del(5)(q13q33) AML relapsing after allogeneic
      hematopoietic SCT.

PMID- 19597425
TI  - Long-term outcome after allo-SCT: close follow-up on a large cohort treated with
      myeloablative regimens.
AB  - We analyzed the late outcomes of 429 long-term survivors post allogeneic
      hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981
      and 2002, and were free of their primary disease for > or =2 years after allo
      HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was
      the primary cause of late death. A total of 37 (8.6%) patients died of non
      relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The
      major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy
      and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence
      (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term
      allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6
      years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The
      endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients,
      osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism
      in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%),
      renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction
      in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as
      treatment for hematological malignancy and who are free of their original disease
      2 years post transplant, mortality is low and the probability of durable
      remission is high. Lifelong surveillance is recommended.

PMID- 19597426
TI  - A case of severe cutaneous, GI and liver GVHD in a patient with multiple myeloma,
      status-post-second auto-SCT.

PMID- 19597427
TI  - Long-term follow-up of patients with diffuse large B-cell non-Hodgkin's lymphoma
      receiving purged autografts after induction failure.
AB  - Patients with diffuse large B-cell lymphoma (DLBCL) who do not achieve a complete
      response to front-line combination chemotherapy are often offered high-dose
      therapy and autologous hematopoietic cell transplantation (AHCT). However, the
      efficacy of this therapy in this patient population has been addressed in only a
      few published reports. We retrospectively analyzed the outcomes of patients with
      a diagnosis of de novo DLBCL who underwent AHCT at our center between 1988 and
      2002, and identified 43 consecutive patients who had not achieved a CR before
      AHCT, although most showed at least a partial response (PR) to either induction
      or subsequent salvage chemotherapy. A total of 15 patients received a
      conditioning regimen that included high-dose chemotherapy with fractionated TBI
      (FTBI), whereas 28 patients received high-dose chemotherapy only. All autografts
      were treated ex vivo with MoAbs and complement in an effort to remove any
      residual malignant B cells. A total of 33 (77%) patients achieved a CR after
      AHCT. With a median follow-up of 7.3 years, the 5-year OS was 69% and EFS was
      59%. Four patients died from non-relapse mortality. By univariate analyses, the
      following characteristics did not significantly impact OS: disease stage at
      diagnosis, age-adjusted IPI (International Prognostic Index) score, age > or =40
      years, earlier radiotherapy and the use of FTBI in the conditioning regimen.
      These results confirm the long-term efficacy of AHCT for patients with DLBCL
      after induction failure.

PMID- 19597428
TI  - Mannose-binding lectin levels and infections in children after allogeneic
      hematopoietic SCT.
AB  - Mannose-binding lectin (MBL) is an activator of the lectin pathway of the C'
      system and hence an important component of the innate immune system. Although
      reports are conflicting, MBL deficiency has been reported to influence the
      infection susceptibility in hematology/oncology patients or recipients of
      allogeneic hematopoietic SCT (HSCT). MBL levels and the occurrence of infections
      were retrospectively analyzed in 98 pediatric HSCT patients. MBL deficiency in
      recipients was not corrected by HSCT using a donor with normal MBL production. In
      addition, low serum MBL concentrations were not associated with increased
      susceptibility to any type of infections post-HSCT in this cohort of pediatric
      HSCT recipients.

PMID- 19597429
TI  - Successful allo-SCT in a Fanconi anemia patient with renal impairment using
      reduced doses of CY and fludarabine.

PMID- 19597430
TI  - The association between diet and physical activity and subsequent excess weight
      gain and obesity assessed at 5 years of age or older: a systematic review of the
      epidemiological evidence.

PMID- 19597445
TI  - Medication-associated diethylene glycol mass poisoning: a review and discussion
      on the origin of contamination.
AB  - Diethylene glycol (DEG), an extremely toxic chemical, has been implicated as the
      etiologic agent in at least 12 medication-associated mass poisonings over the
      last 70 years. Why DEG mass poisonings occur remains unclear. Most reports do not
      contain detailed reports of trace-back investigations into the etiology. The
      authors, therefore, conducted a systematic literature review on potential
      etiologies of these mass poisonings. The current available evidence suggests that
      substitution of DEG or DEG-containing compounds for pharmaceutical ingredients
      results from: (1) deception as to the true nature of certain ingredients by
      persons at some point in the pharmaceutical manufacturing process, and (2)
      failure to adhere to standardized quality control procedures in manufacturing
      pharmaceutical products intended for consumers. We discuss existing guidelines
      and new recommendations for prevention of these incidents.

PMID- 19597446
TI  - Assessing lung function and respiratory health in schoolchildren as a means to
      improve local environmental conditions.
AB  - In response to the World Health Organization Children's Environment and Health
      Action Plan for Europe (CEHAPE), a town near Vienna initiated a health survey of
      schoolchildren. To create recommendations for the community's decision makers,
      the health survey tried to identify the environmental factors influencing the
      respiratory health of children. The survey consisted of a questionnaire and
      spirometry. For 186 of 207 children of first and second grade, parents consented
      to include their children and answered a questionnaire. Spirometry was performed
      in 177 children. Results of lung function testing revealed that lung function was
      significantly reduced in children with visible mould infestation at home and
      living on a street with frequent lorry traffic. Larger family size and living in
      a rural area had positive effects on lung function. Our study provides an example
      for a feasible strategy to provide local decision makers with recommendations
      based on scientific evidence and actual observations and to help them implement
      measures in accordance with CEHAPE.

PMID- 19597447
TI  - Protecting our children's health: The ultimate government 'stimulus package'.
AB  - The Children's Environment and Health Action Plan for Europe has established four
      Regional Priority Goals (RPG) for the protection of the health of children.
      Hutter et al (JPHP 2009) have developed and tested an accessible method for
      addressing one aspect of RPG III: indoor and outdoor air pollution. The study
      provides an accessible method for use by communities to access effects of air
      pollution in and around the home on the respiratory health of children. This
      Commentary reviews that study, as well as other evidence in the scientific
      literature of effects of indoor and outdoor air pollution on children's
      respiratory health. In addition, this Commentary discusses the importance of air
      quality in schools to children's respiratory health and to school attendance and
      performance, citing supportive dat and urging action on this front.

PMID- 19597448
TI  - Against unjust global distribution of power and money: the report of the WHO
      commission on the social determinants of health: global inequality and the future
      of public health policy.
AB  - In 2008, the World Health Organization (WHO) released the report of its
      Commission on Social Determinants of Health--Closing the Gap in a Generation. We
      describe how the report was initially received, what went into shaping the report
      during the months of its preparation and what more can be done now to realize the
      ultimate goal: population-level reduction in inequalities. As we find the Report
      to be strong in its presentation of evidence but weak in its policy
      recommendations, we present our own recommendations for research and action. From
      our perspectives within the increasingly visible field of social determinants of
      health research, we address this question: how can research improve the ability
      of public health policymakers to implement the Report's suggestions, plus develop
      new and better ones?

PMID- 19597449
TI  - Equity and health services.
AB  - The Commission on Social Determinants of Health recognized the important role of
      health services as a determinant of health. While asserting that health was not a
      tradable commodity but rather a right, the Commission missed an opportunity to
      address how such a concept might remove a health care system from market forces.
      Examples include ensuring universal access to health care, not just universal
      insurance, severely limiting or eliminating profit-making in the delivery of
      health care services, and aggressive price regulations for the public good. While
      the Commission was appropriately sceptical of privileging efficiency as a
      principle for prioritization, it missed an opportunity to address how equity
      concerns can be incorporated into resources allocation decision making. A social
      justice orientation to the delivery of health care could serve as an important
      catalyst for equity-oriented health service change but the process is more
      complicated and political than that outlined in the Commission's report.

PMID- 19597450
TI  - Closing the gap in urban health inequities.

PMID- 19597451
TI  - Social inequalities in health and closing the gap in a generation.

PMID- 19597452
TI  - Labor markets and social determinants of health.

PMID- 19597454
TI  - The tobacco excise system in Indonesia: hindering effective tobacco control for
      health.
AB  - Comprehensive tobacco control policies include high taxes. This paper describes
      the tobacco excise structure in Indonesia from 2007 to 2009. The design of the
      tobacco excise system contributes to neutralizing the effect of a tax increase on
      consumption. Wide gaps in tax rates allow for the availability of low-priced
      products, and consumers can substitute to cheaper products in response to price
      increases. There has been no systematic increase in the tax rates, which promotes
      affordable of tobacco products. Firms can reduce their prices at point of sale
      and absorb the tax increase instead of passing it onto consumers. Tiered tax
      rates by production scale allow firms to evade paying the highest tax brackets
      legally, thereby increasing profit margins while reducing prices at point of
      sale. Increases in tobacco excise rates in Indonesia may not have a large health
      impact under the current system of tax administration.

PMID- 19597455
TI  - Motorcycle helmets and rider safety: a legislative crisis.
AB  - Over the past four decades, motorcycle helmet laws within the United States have
      been in a state of flux and have been shaped by the conflicting influences of the
      federal government's initiatives to shape state policies and motorcycle
      advocates' persistent lobbying efforts. Examination of individual state
      experiences with motorcycle helmet legislation demonstrates that universal
      motorcycle helmet laws effectively promote helmet use compliance, reduce
      morbidity and mortality in motorcycle crashes, and lower the health care costs
      and associated societal burdens of these crash victims. Motorcycle advocates have
      challenged the implementation of these laws and directly influenced the weakening
      or frank repeal of these laws to negative consequence. We offer this review as an
      educational resource to encourage and facilitate health care worker participation
      in legislative efforts to support implementation and maintenance of universal
      motorcycle helmet laws.

PMID- 19597453
TI  - Bringing health and social policy together: the case of the earned income tax
      credit.
AB  - The principal objective of our research is to examine whether the earned income
      tax credit (EITC), a broad-based income support program that has been shown to
      increase employment and income among poor working families, also improves their
      health and access to care. A finding that the EITC has a positive impact on the
      health of the American public may help guide deliberations about its future at
      the federal, state, and local levels. The authors contend that a better
      understanding of the relationship between major socioeconomic policies such as
      the EITC and the public's health will inform the fields of health and social
      policy in the pursuit of improving population health.

PMID- 19597456
TI  - Minimizing the health impacts of the global financial crisis.

PMID- 19597458
TI  - Global health training is not only a developed-country duty.

PMID- 19597459
TI  - International, transnational, and global health; do they differ?

PMID- 19597460
TI  - A new p63-deficient mouse model or a fresh look at an old one?

PMID- 19597461
TI  - International EMBO Workshop on 'Model Organisms in Cell Death Research',
      Obergurgl (Austria).

PMID- 19597462
TI  - Redox regulation in acute and chronic inflammation.

PMID- 19597464
TI  - 5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression
      network sensing actin dynamics.
AB  - Complete loss or interstitial deletions of chromosome 5 are the most common
      karyotypic abnormality in myelodysplastic syndromes (MDSs). Isolated del(5q)/5q-
      MDS patients have a more favorable prognosis than those with additional
      karyotypic defects, who tend to develop myeloproliferative neoplasms (MPNs) and
      acute myeloid leukemia. The frequency of unbalanced chromosome 5 deletions has
      led to the idea that 5q harbors one or more tumor-suppressor genes that have
      fundamental roles in the growth control of hematopoietic stem/progenitor cells
      (HSCs/HPCs). Cytogenetic mapping of commonly deleted regions (CDRs) centered on
      5q31 and 5q32 identified candidate tumor-suppressor genes, including the
      ribosomal subunit RPS14, the transcription factor Egr1/Krox20 and the
      cytoskeletal remodeling protein, alpha-catenin. Although each acts as a tumor
      suppressor, alone or in combination, no molecular mechanism accounts for how
      defects in individual 5q candidates may act as a lesion driving MDS or
      contributing to malignant progression in MPN. One candidate gene that resides
      between the conventional del(5q)/5q- MDS-associated CDRs is DIAPH1 (5q31.3).
      DIAPH1 encodes the mammalian Diaphanous-related formin, mDia1. mDia1 has critical
      roles in actin remodeling in cell division and in response to adhesive and
      migratory stimuli. This review examines evidence, with a focus on mouse gene
      targeting experiments, that mDia1 acts as a node in a tumor-suppressor network
      that involves multiple 5q gene products. The network has the potential to sense
      dynamic changes in actin assembly. At the root of the network is a
      transcriptional response mechanism mediated by the MADS-box transcription factor,
      serum response factor (SRF), its actin-binding myocardin family coactivator, MAL,
      and the SRF-target 5q gene, EGR1, which regulate the expression of PTEN and p53
      family tumor-suppressor proteins. We hypothesize that the network provides a
      homeostatic mechanism balancing HPC/HSC growth control and differentiation
      decisions in response to microenvironment and other external stimuli.

PMID- 19597463
TI  - Cancer targeted gene therapy of BikDD inhibits orthotopic lung cancer growth and
      improves long-term survival.
AB  - Lung cancer is a leading cause of cancer death due to the high incidence of
      metastasis; therefore, novel and effective treatments are urgently needed. A
      current strategy is cancer-specific targeted gene therapy. Although many
      identified that cancer-specific promoters are highly specific, they tend to have
      low activity compared with the ubiquitous cytomegalovirus (CMV) promoter,
      limiting their application. We developed a targeted gene therapy expression
      system for lung cancer that is highly specific with strong activity. Our
      expression vector uses the survivin promoter, highly expressed in many cancers
      but not normal adult tissues. We enhanced the survivin promoter activity
      comparable to the CMV promoter in lung cancer cell lines using an established
      platform technology, whereas the survivin promoter remained weak in normal cells.
      In mouse models, the transgene was specifically expressed in the lung tumor
      tissue, compared with the CMV promoter that was expressed in both normal and
      tumor tissues. In addition, the therapeutic gene BikDD, a mutant form of pro
      apoptotic Bcl2 interacting killer, induced cell killing in vitro, and inhibited
      cell growth and prolonged mouse survival in vivo. Importantly, there was
      virtually no toxicity when BikDD was expressed with our expression system. Thus,
      the current report provides a therapeutic efficacy and safe strategy worthy of
      development in clinical trials treating lung cancer.

PMID- 19597465
TI  - Loss of Nkx3.1 leads to the activation of discrete downstream target genes during
      prostate tumorigenesis.
AB  - The expression of NKX3.1, a transcriptional regulator and tumor suppressor gene
      in prostate cancer, is downregulated during early stages of prostate
      tumorigenesis. However, little is known of the alterations in gene expression
      that occur as a result of this event. We combined laser capture microdissection
      and gene expression profiling to analyse the molecular consequences of Nkx3.1
      loss during prostate cancer initiation using Nkx3.1-deficient mice. This analysis
      identified a cohort of genes (loss-of-Nkx3.1 signature) that are aberrantly
      overexpressed during loss-of-Nkx3.1-driven tumor initiation. We studied the
      expression of these genes in independent loss-of-Pten and c-myc overexpression
      prostate adenocarcinoma mouse models. Nkx3.1 expression is lost in prostate
      epithelial proliferation in both of these mouse models. However, Nkx3.1 loss is
      an early event of tumor development in the loss-of-Pten model, whereas it occurs
      at later stages in c-myc transgenic mice. A number of genes of the loss-of-Nkx3.1
      signature, such as clusterin and quiescin Q6, are highly expressed in prostatic
      hyperplasia and intraepithelial neoplasia (PIN) lesions that also lack Nkx3.1 in
      the Pten-deficient prostate, but not in similar lesions in the c-myc transgenic
      model. Meta-analysis of multiple prostate cancer gene expression data sets,
      including those from loss-of-Nkx3.1, loss-of-Pten, c-myc overexpression and
      constitutively active Akt prostate cancer models, further confirmed that genes
      associated with the loss-of-Nkx3.1 signature integrate with PTEN-AKT signaling
      pathways, but do not overlap with molecular changes associated with the c-myc
      signaling pathway. In human prostate tissue samples, loss of NKX3.1 expression
      and corresponding clusterin overexpression are co-localized at sites of prostatic
      inflammatory atrophy, a possible very early stage of human prostate
      tumorigenesis. Collectively, these results suggest that the molecular
      consequences of NKX3.1 loss depend on the epithelial proliferative stage at which
      its expression is lost, and that alterations in the PTEN-AKT-NKX3.1 axis are
      important for prostate cancer initiation.

PMID- 19597466
TI  - Lithium suppresses motility and invasivity of v-src-transformed cells by
      glutathione-dependent activation of phosphotyrosine phosphatases.
AB  - Lithium has long been used for the treatment and prophylaxis of bipolar mood
      disorder. However, nerve cells are not the sole targets of lithium. Indeed,
      lithium was reported to target numerous cell types, and affect cell
      proliferation, differentiation and death. Thus, the idea has been raised that
      lithium may act on signaling pathways involved in neoplastic transformation.
      Indeed, the effect of lithium on tumor progression is currently being tested in a
      limited number of clinical trials. However, the molecular mechanisms by which
      lithium affects neoplastic transformation remain to be characterized. Here, using
      mouse fibroblasts transformed by the v-src oncogene as a model, we show that
      lithium drastically inhibits cell motility and compromises the invasive phenotype
      of v-src-transformed cells. In addition, we show that this effect is mediated by
      the activation of phosphotyrosine phosphatases, but not by the direct inhibition
      of the v-Src tyrosine kinase. Finally, we show that lithium activates
      phosphotyrosine phosphatases by the modulation of the redox status of the cell,
      independently of the Wnt and the inositol phosphate canonical pathways. Thus,
      this study supports the idea that lithium, acting similar to an antioxydizer, may
      have antimetastatic properties in vivo.

PMID- 19597467
TI  - Genetic predisposition to human disease: allele-specific expression and low
      penetrance regulatory loci.
AB  - The two alleles of a gene can be expressed at different levels, the extreme
      example being imprinting, a condition in which one allele is totally suppressed.
      Recently, subtle differences in the expression of the two alleles have been
      detected in numerous human genes and in a few cases, have been associated with a
      genetic predisposition to disease. The underlying mechanisms are largely
      unexplored.

PMID- 19597469
TI  - Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in
      endothelial cells.
AB  - Angiogenesis is a key step in tumor growth and metastasis. The mechanism by which
      osteopontin (OPN) induces the angiogenesis of endothelial cells remains unclear.
      Here, we show that OPN confers cytoprotection through the activation of the
      PI3K/Akt pathway with subsequent upregulation of Bcl-xL and activation of nuclear
      factor-kappaB. OPN enhances the expression of vascular endothelial growth factor
      (VEGF) through the phosphorylation of AKT and extracellular signal-regulated
      kinase (ERK). In turn, OPN-induced VEGF activates PI3K/AKT and the ERK1/2 pathway
      as a positive feedback signal. Blocking the feedback signal by anti-VEGF
      antibody, PI3-kinase inhibitor or ERK inhibitor can partially inhibit the OPN
      induced human umbilical vein endothelial cell (HUVEC) motility, proliferation and
      tube formation, while blocking the signal by anti-OPN or anti-alphavbeta3
      antibody completely abrogates the biological effects of OPN on HUVECs. In
      addition, blood vessel formation is also investigated in vivo. The
      antiangiogenesis efficacy of anti-OPN antibody in vivo is more effective than
      that of anti-VEGF antibody, which only blocks the feedback signals. These data
      show that OPN enhances angiogenesis directly through PI3K/AKT- and ERK-mediated
      pathways with VEGF acting as a positive feedback signal. The results suggest that
      OPN might be a valuable target for developing novel antiangiogenesis therapy for
      treatment of cancer.

PMID- 19597470
TI  - MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer
      cells through E2F1-mediated suppression of Akt phosphorylation.
AB  - MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as
      oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes.
      A recent study that analysed a large number of human cancer cell lines showed
      that miR-330 is a potential tumor-suppressor gene. However, the function and
      molecular mechanism of miR-330 in determining the aggressiveness of human
      prostate cancer has not been studied. Here, we show that miR-330 is significantly
      lower expressed in human prostate cancer cell lines than in nontumorigenic
      prostate epithelial cells. Bioinformatics analyses reveal a conserved target site
      for miR-330 in the 3'-untranslated region (UTR) of E2F1 at nucleotides 1018-1024.
      MiR-330 significantly suppressed the activity of a luciferase reporter containing
      the E2F1-3'-UTR in the cells. This activity could be abolished with the
      transfection of anti-miR-330 or mutated E2F1-3'-UTR. In addition, the expression
      level of miR-330 and E2F1 was inversely correlated in cell lines and prostate
      cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was
      suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing
      apoptosis. Collectively, this is the first study to show that E2F1 is negatively
      regulated by miR-330 and also show that miR-330 induces apoptosis in prostate
      cancer cells through E2F1-mediated suppression of Akt phosphorylation.

PMID- 19597468
TI  - Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin.
AB  - The development of pulmonary metastasis is the major cause of death in
      osteosarcoma, and its molecular basis is poorly understood. In this study, we
      show that beta4 integrin is highly expressed in human osteosarcoma cell lines and
      tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased
      levels of beta4 integrin. Suppression of beta4 integrin expression by shRNA and
      disruption of beta4 integrin function by transfection of dominant-negative beta4
      integrin was sufficient to revert this highly metastatic phenotype in the MNNG
      HOS model without significantly affecting primary tumor growth. These findings
      suggest a role for beta4 integrin expression in the metastatic phenotype in human
      osteosarcoma cells. In addition, we identified a previously uncharacterized
      interaction between beta4 integrin and ezrin, a membrane-cytoskeletal linker
      protein that is implicated in the metastatic behavior of osteosarcoma. The beta4
      integrin-ezrin interaction appears to be critical for maintenance of beta4
      integrin expression. These data begin to integrate ezrin and beta4 integrin
      expression into a model of action for the mechanism of osteosarcoma metastases.

PMID- 19597472
TI  - Histone deacetylase inhibitors cooperate with IFN-gamma to restore caspase-8
      expression and overcome TRAIL resistance in cancers with silencing of caspase-8.
AB  - Evasion of apoptosis can be caused by epigenetic silencing of caspase-8, a key
      component of the extrinsic apoptosis pathway. Loss of caspase-8 correlates with
      poor prognosis in medulloblastoma, which highlights the relevance of strategies
      to upregulate caspase-8 to break apoptosis resistance. Here, we develop a new
      combinatorial approach, that is treatment using histone deacetylase inhibitors
      (HDACI) together with interferon (IFN)-gamma, to restore caspase-8 expression and
      to overcome resistance to the death-receptor ligand TNF-related apoptosis
      inducing ligand (TRAIL) in medulloblastoma in vitro and in vivo. HDACI, for
      example, valproic acid (VA), suberoylanilide hydroxamic acid (SAHA) and MS-275,
      cooperate with IFN-gamma to upregulate caspase-8 in cancer cells lacking caspase
      8, thereby restoring sensitivity to TRAIL-induced apoptosis. Molecular studies
      show that VA promotes histone acetylation and acts in concert with IFN-gamma to
      stimulate caspase-8 promoter activity. The resulting increase in caspase-8 mRNA
      and protein expression leads to enhanced TRAIL-induced activation of caspase-8 at
      the death-inducing signaling complex, mitochondrial outer-membrane
      permeabilization and caspase-dependent cell death. Intriguingly, pharmacological
      or genetic inhibition of caspase-8 also abolishes the VA/IFN-gamma-mediated
      sensitization for TRAIL-induced apoptosis. It is important to note that VA and
      IFN-gamma restore caspase-8 expression and sensitivity to TRAIL in primary
      medulloblastoma samples and significantly potentiate TRAIL-mediated suppression
      of medulloblastoma growth in vivo. These findings provide the rationale for
      further (pre)clinical evaluation of VA and IFN-gamma to restore caspase-8
      expression and apoptosis sensitivity in cancers with caspase-8 silencing and open
      new perspectives to overcome TRAIL resistance.

PMID- 19597471
TI  - Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that
      target FGF-2-cell binding and signaling.
AB  - Enhanced RAS signaling and decreased androgen dependence of prostate cancer cells
      accompany poor clinical outcomes. Elevated autocrine fibroblast growth factors 2
      (FGF-2) signaling promotes prostate cancer cell growth and survival. Expression
      of lysyl oxidase (LOX) inhibits RAS transforming activity. LOX is secreted as 50
      kDa pro-LOX protein and then undergoes extracellular proteolytic processing to
      form approximately 30 kDa LOX enzyme and approximately 18 kDa propeptide (LOX
      PP). We have previously shown that LOX-PP inhibits breast cancer cell
      transformation and tumor formation, but mechanisms of action of LOX-PP have not
      been fully elucidated. Here we report that LOX expression is reduced in prostate
      cancer cell lines and that recombinant LOX-PP protein inhibits serum-stimulated
      DNA synthesis and MEK/ERK and PI3K/AKT pathways in DU 145 and PC-3 androgen
      independent cell lines. In DU 145 cells, treatment with a pharmacologic FGF
      receptor inhibitor or a neutralizing anti-FGFR1 antibody mimicked LOX-PP
      inhibition of serum-stimulated DNA synthesis. FGF-2-stimulated DNA synthesis,
      ERK1/2, AKT and FRS2alpha activation were found all to be inhibited by LOX-PP in
      DU 145 cells. LOX-PP reduced specific binding of FGF-2 to DU 145 cells,
      suggesting that LOX-PP targets FGF signaling at the receptor. Interestingly, PC-3
      cells did not respond to FGF-2, consistent with previous reports. We conclude
      that LOX-PP inhibits proliferation of DU 145 cells by interfering with FGFR(s)
      binding and signaling, and that LOX-PP has other mechanisms of action in PC-3
      cells.

PMID- 19597473
TI  - Counterbalance between RB inactivation and miR-17-92 overexpression in reactive
      oxygen species and DNA damage induction in lung cancers.
AB  - Small-cell lung cancer (SCLC) is a highly aggressive disease that exhibits rapid
      growth and genetic instability. We found earlier frequent overexpression of the
      miR-17-92 microRNA cluster, and showed that SCLC cells were addicted to continued
      expressions of miR-17-5p and miR-20a, major components of this microRNA cluster.
      In this study, we identified the frequent presence of constitutively
      phosphorylated H2AX (gamma-H2AX), which reflects continuing DNA damage,
      preferentially in SCLC. Knockdown of RB induced gamma-H2AX foci formation in non
      small cell lung cancer (NSCLC) cells with wild-type RB, in association with
      growth inhibition and reactive oxygen species (ROS) generation, which was
      canceled by overexpression of miR-17-92. Conversely, induction of gamma-H2AX was
      observed in a miR-17-92-overexpressing SCLC cell line with miR-20a antisense
      oligonucleotides. These findings suggest that miR-17-92 overexpression may serve
      as a fine-tuning influence to counterbalance the generation of DNA damage in RB
      inactivated SCLC cells, thus reducing excessive DNA damage to a tolerable level
      and consequently leading to genetic instability. Therefore, miR-17-92 may be an
      excellent therapeutic target candidate to elicit excessive DNA damage in
      combination with DNA-damaging chemotherapeutics.

PMID- 19597474
TI  - The role of SPARC in the TRAMP model of prostate carcinogenesis and progression.
AB  - SPARC (Secreted Protein Acidic and Rich in Cysteine), is a matricellular
      glycoprotein that is produced by tumor and/or neighboring stroma. In human
      prostate cancer, SPARC immunoreactivity is highest in metastatic lesions but
      distinct contributions of tumoral and stromal SPARC to tumorigenesis and
      progression are unclear. To determine the role of SPARC in primary prostate
      tumorigenesis, we crossed SPARC-null (SP(-/-)) with TRAMP (Transgenic
      Adenocarcinoma of Mouse Prostate) mice. TRAMP(+)/SP(-/-) mice exhibited
      accelerated cancer development and progression. Compared to their TRAMP(+)/SP(-/
      ) counterparts, TRAMP(+)/SP(+/+) tumors had fewer proliferating cells, and
      decreased cyclins A and D1 with increased p21(Cip) and p27(Kip). Similar effects
      on proliferation and cell-cycle regulators were observed in human prostate cancer
      cell lines, transiently transfected with pSPARC. TRAMP(+)/SP(-/-) tumors
      exhibited decreased stromal collagen, enhanced matrix metalloproteinase activity
      and increased vascular endothelial growth factor, proinflammatory cytokines. To
      determine the contribution of stromal SPARC, we evaluated subcutaneous tumor
      growth of TRAMP cell lines in syngeneic SP(+/+) and SP(-/-) mice. Enhanced
      growth, decreased stromal collagen and increased proteolysis were noted in SP(-/
      ) mice. Our findings demonstrate that both tumor and stromal SPARC are limiting
      for primary prostate tumorigenesis and progression, through effects on the cell
      cycle and the creation of a less favorable tumor microenvironment.

PMID- 19597476
TI  - Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1
      and thereby modulates the transcription factor activity.
AB  - Heat shock protein 27 (HSP27) accumulates in stressed cells and helps them to
      survive adverse conditions. We have already shown that HSP27 has a function in
      the ubiquitination process that is modulated by its
      oligomerization/phosphorylation status. Here, we show that HSP27 is also involved
      in protein sumoylation, a ubiquitination-related process. HSP27 increases the
      number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3 but
      this effect shows some selectivity as it neither affects all proteins nor
      concerns SUMO-1. Moreover, no such alteration in SUMO-2/3 conjugation is
      achievable by another HSP, such as HSP70. Heat shock factor 1 (HSF1), a
      transcription factor responsible for HSP expression, is one of the targets of
      HSP27. In stressed cells, HSP27 enters the nucleus and, in the form of large
      oligomers, binds to HSF1 and induces its modification by SUMO-2/3 on lysine 298.
      HSP27-induced HSF1 modification by SUMO-2/3 takes place downstream of the
      transcription factor phosphorylation on S303 and S307 and does not affect its DNA
      binding ability. In contrast, this modification blocks HSF1 transactivation
      capacity. These data show that HSP27 exerts a feedback inhibition of HSF1
      transactivation and enlighten the strictly regulated interplay between HSPs and
      HSF1. As we also show that HSP27 binds to the SUMO-E2-conjugating enzyme, Ubc9,
      our study raises the possibility that HSP27 may act as a SUMO-E3 ligase specific
      for SUMO-2/3.

PMID- 19597475
TI  - PML involvement in the p73-mediated E1A-induced suppression of EGFR and induction
      of apoptosis in head and neck cancers.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase is commonly overexpressed
      in human cancers; however, the cellular mechanisms regulating EGFR expression
      remain unclear. p53, p63 and p73 are transcription factors regulating many
      cellular targets involved in controlling the cell cycle and apoptosis. p53
      activates EGFR expression, whereas TAp63 represses EGFR transcription. The
      involvement of p73 in the regulation of EGFR has not been reported. Here, a
      strong correlation between EGFR overexpression and increased levels of the
      oncogenic DeltaNp73 isoform in head and neck squamous cell carcinoma (HNSCC) cell
      lines was observed. Ectopic expression of TAp73, particularly TAp73beta, resulted
      in suppression of the EGFR promoter, significant downregulation of EGFR protein
      and efficient induction of cell death in all six EGFR-overexpressing HNSCC cell
      lines. EGFR overexpression from a heterologous LTR promoter protected lung cancer
      cells from TAp73beta-induced EGFR suppression and apoptosis. Expression of
      TAp73beta efficiently induced promyelocytic leukaemia (PML) protein expression
      and PML knockdown by shRNA attenuated the downregulation of EGFR and induction of
      apoptosis by p73 in HNSCC cells. Furthermore, PML was found to be important for
      E1A-induced suppression of EGFR and subsequent killing of HNSCC cells. Our data
      therefore suggest a novel pathway involving PML and p73 in the regulation of EGFR
      expression.

PMID- 19597477
TI  - Pelvic claspers confirm chondrichthyan-like internal fertilization in
      arthrodires.
AB  - Recent finds demonstrate that internal fertilization and viviparity (live birth)
      were more widespread in the Placodermi, an extinct group of armoured fishes, than
      was previously realized. Placoderms represent the sister group of the crown group
      jawed vertebrates (Gnathostomata), making their mode(s) of reproduction
      potentially informative about primitive gnathostome conditions. An ossified
      pelvic fin basipterygium discovered in the arthrodire Incisoscutum ritchiei was
      hypothesized to be identical in males and females, with males presumed to have an
      additional cartilaginous element or series forming a clasper. Here we report the
      discovery of a completely ossified pelvic clasper in Incisoscutum ritchiei (WAM
      03.3.28) which shows that this interpretation was incorrect: the basipterygium
      described previously is in fact unique to females. The male clasper is a slender
      rod attached to a square basal plate that articulates directly with the pelvis.
      It carries a small cap of dermal bone covered in denticles and small hooks that
      may be homologous with the much larger dermal component of the ptyctodont
      clasper.

PMID- 19597478
TI  - EBI2 mediates B cell segregation between the outer and centre follicle.
AB  - B cell follicles are specialized microenvironments that support events necessary
      for humoral immunity. After antigen encounter, activated B cells initially seek T
      cell help at the follicle-T-zone boundary and then move to interfollicular and T
      zone distal (outer) regions of the follicle. Subsequently, some cells move to the
      follicle centre, become germinal centre B cells and undergo antibody affinity
      maturation. Although germinal centres within follicles were described in 1885
      (ref. 12), the molecular cues mediating segregation of B cells between the outer
      and centre follicle have remained undefined. Here we present a role for the
      orphan G-protein-coupled receptor, Epstein-Barr virus induced molecule-2 (EBI2,
      also known as GPR183), in this process. EBI2 is expressed in mature B cells and
      increases in expression early after activation, before being downregulated in
      germinal centre B cells. EBI2 deficiency in mice led to a reduction in the early
      antibody response to a T-dependent antigen. EBI2-deficient B cells failed to move
      to the outer follicle at day 2 of activation, and instead were found in the
      follicle centre, whereas EBI2 overexpression was sufficient to promote B cell
      localization to the outer follicle. In mixed bone marrow chimaeras, EBI2
      deficient B cells phenocopied germinal centre B cells in preferentially
      localizing to the follicle centre. When downregulation of EBI2 in wild-type B
      cells was antagonized, participation in the germinal centre reaction was
      impaired. These studies identify an important role for EBI2 in promoting B cell
      localization in the outer follicle, and show that differential expression of this
      receptor helps position B cells appropriately for mounting T-dependent antibody
      responses.

PMID- 19597479
TI  - Switch in FGF signalling initiates glial differentiation in the Drosophila eye.
AB  - The formation of a complex nervous system requires the intricate interaction of
      neurons and glial cells. Glial cells generally migrate over long distances before
      they initiate their differentiation, which leads to wrapping and insulation of
      axonal processes. The molecular pathways coordinating the switch from glial
      migration to glial differentiation are largely unknown. Here we demonstrate that,
      within the Drosophila eye imaginal disc, fibroblast growth factor (FGF)
      signalling coordinates glial proliferation, migration and subsequent axonal
      wrapping. Glial differentiation in the Drosophila eye disc requires a succession
      from glia-glia interaction to glia-neuron interaction. The neuronal component of
      the fly eye develops in the peripheral nervous system within the eye-antennal
      imaginal disc, whereas glial cells originate from a pool of central-nervous
      system-derived progenitors and migrate onto the eye imaginal disc. Initially,
      glial-derived Pyramus, an FGF8-like ligand, modulates glial cell number and
      motility. A switch to neuronally expressed Thisbe, a second FGF8-like ligand,
      then induces glial differentiation. This switch is accompanied by an alteration
      in the intracellular signalling pathway through which the FGF receptor channels
      information into the cell. Our findings reveal how a switch from glia-glia
      interactions to glia-neuron interactions can trigger formation of glial membrane
      around axonal trajectories. These results disclose an evolutionarily conserved
      control mechanism of axonal wrapping, indicating that Drosophila might serve as a
      model to understand glial disorders in humans.

PMID- 19597480
TI  - Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human
      cell extracts.
AB  - Expansion of CAG/CTG trinucleotide repeats is associated with certain familial
      neurological disorders, including Huntington's disease. Increasing evidence
      suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA
      metabolism contributes to their expansion. However, the molecular mechanism(s) by
      which cells remove CAG/CTG hairpins remain unknown. Here we demonstrate that
      human cell extracts can catalyze error-free repair of CAG/CTG hairpins in a nick
      directed manner. The repair system specifically targets CAG/CTG tracts for
      incisions in the nicked DNA strand, followed by DNA resynthesis using the
      continuous strand as a template, thereby ensuring CAG/CTG stability.
      Proliferating cell nuclear antigen (PCNA) is required for the incision step of
      the hairpin removal, which uses distinct endonuclease activities for individual
      CAG/CTG hairpins depending on their strand locations and/or secondary structures.
      We discuss the implications of these data for understanding the etiology of
      neurological diseases and trinucleotide repeat instability.

PMID- 19597481
TI  - Structural and functional analyses of minimal phosphopeptides targeting the polo
      box domain of polo-like kinase 1.
AB  - Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is
      considered a potential target for anticancer therapy. The noncatalytic polo-box
      domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein
      interaction. Here, we report the identification of minimal phosphopeptides that
      specifically interact with the PBD of human PLK1, but not those of the closely
      related PLK2 and PLK3. Comparative binding studies and analyses of crystal
      structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed
      that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas
      the N-terminal residues are crucial for providing specificity and affinity to the
      interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was
      sufficient to induce mitotic arrest and apoptotic cell death. The mode of
      interaction between the minimal peptide and PBD may provide a template for
      designing therapeutic agents that target PLK1.

PMID- 19597483
TI  - Translation factors direct intrinsic ribosome dynamics during translation
      termination and ribosome recycling.
AB  - Characterizing the structural dynamics of the translating ribosome remains a
      major goal in the study of protein synthesis. Deacylation of peptidyl-tRNA during
      translation elongation triggers fluctuations of the pretranslocation ribosomal
      complex between two global conformational states. Elongation factor G-mediated
      control of the resulting dynamic conformational equilibrium helps to coordinate
      ribosome and tRNA movements during elongation and is thus a crucial mechanistic
      feature of translation. Beyond elongation, deacylation of peptidyl-tRNA also
      occurs during translation termination, and this deacylated tRNA persists during
      ribosome recycling. Here we report that specific regulation of the analogous
      conformational equilibrium by translation release and ribosome recycling factors
      has a critical role in the termination and recycling mechanisms. Our results
      support the view that specific regulation of the global state of the ribosome is
      a fundamental characteristic of all translation factors and a unifying theme
      throughout protein synthesis.

PMID- 19597482
TI  - Diversity of chemical mechanisms in thioredoxin catalysis revealed by single
      molecule force spectroscopy.
AB  - Thioredoxins (Trxs) are oxidoreductase enzymes, present in all organisms, that
      catalyze the reduction of disulfide bonds in proteins. By applying a calibrated
      force to a substrate disulfide, the chemical mechanisms of Trx catalysis can be
      examined in detail at the single-molecule level. Here we use single-molecule
      force-clamp spectroscopy to explore the chemical evolution of Trx catalysis by
      probing the chemistry of eight different Trx enzymes. All Trxs show a
      characteristic Michaelis-Menten mechanism that is detected when the disulfide
      bond is stretched at low forces, but at high forces, two different chemical
      behaviors distinguish bacterial-origin from eukaryotic-origin Trxs. Eukaryotic
      origin Trxs reduce disulfide bonds through a single-electron transfer reaction
      (SET), whereas bacterial-origin Trxs show both nucleophilic substitution (S(N)2)
      and SET reactions. A computational analysis of Trx structures identifies the
      evolution of the binding groove as an important factor controlling the chemistry
      of Trx catalysis.

PMID- 19597484
TI  - Differential requirements for actin during yeast and mammalian endocytosis.
AB  - Key features of clathrin-mediated endocytosis have been conserved across
      evolution. However, endocytosis in Saccharomyces cerevisiae is completely
      dependent on a functional actin cytoskeleton, whereas actin appears to be less
      critical in mammalian cell endocytosis. We reveal that the fundamental
      requirement for actin in the early stages of yeast endocytosis is to provide a
      strong framework to support the force generation needed to direct the
      invaginating plasma membrane into the cell against turgor pressure. By providing
      osmotic support, pressure differences across the plasma membrane were removed and
      this reduced the requirement for actin-bundling proteins in normal endocytosis.
      Conversely, increased turgor pressure in specific yeast mutants correlated with a
      decreased rate of endocytic patch invagination.

PMID- 19597485
TI  - The CDK4-pRB-E2F1 pathway controls insulin secretion.
AB  - CDK4-pRB-E2F1 cell-cycle regulators are robustly expressed in non-proliferating
      beta cells, suggesting that besides the control of beta-cell number the CDK4-pRB
      E2F1 pathway has a role in beta-cell function. We show here that E2F1 directly
      regulates expression of Kir6.2, which is a key component of the K(ATP) channel
      involved in the regulation of glucose-induced insulin secretion. We demonstrate,
      through chromatin immunoprecipitation analysis from tissues, that Kir6.2
      expression is regulated at the promoter level by the CDK4-pRB-E2F1 pathway.
      Consistently, inhibition of CDK4, or genetic inactivation of E2F1, results in
      decreased expression of Kir6.2, impaired insulin secretion and glucose
      intolerance in mice. Furthermore we show that rescue of Kir6.2 expression
      restores insulin secretion in E2f1(-/-) beta cells. Finally, we demonstrate that
      CDK4 is activated by glucose through the insulin pathway, ultimately resulting in
      E2F1 activation and, consequently, increased expression of Kir6.2. In summary we
      provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose
      homeostasis, defining a new link between cell proliferation and metabolism.

PMID- 19597486
TI  - A two-step model for senescence triggered by a single critically short telomere.
AB  - Telomeres protect chromosome ends from fusion and degradation. In the absence of
      a specific telomere elongation mechanism, their DNA shortens progressively with
      every round of replication, leading to replicative senescence. Here, we show that
      telomerase-deficient cells bearing a single, very short telomere senesce earlier,
      demonstrating that the length of the shortest telomere is a major determinant of
      the onset of senescence. We further show that Mec1p-ATR specifically recognizes
      the single, very short telomere causing the accelerated senescence. Strikingly,
      before entering senescence, cells divide for several generations despite complete
      erosion of their shortened telomeres. This pre-senescence growth requires RAD52
      (radiation sensitive) and MMS1 (methyl methane sulfonate sensitive), and there is
      no evidence for major inter-telomeric recombination. We propose that, in the
      absence of telomerase, a very short telomere is first maintained in a pre
      signalling state by a RAD52-MMS1-dependent pathway and then switches to a
      signalling state leading to senescence through a Mec1p-dependent checkpoint.

PMID- 19597487
TI  - The DNA damage response at eroded telomeres and tethering to the nuclear pore
      complex.
AB  - The ends of linear eukaryotic chromosomes are protected by telomeres, which serve
      to ensure proper chromosome replication and to prevent spurious recombination at
      chromosome ends. In this study, we show by single cell analysis that in the
      absence of telomerase, a single short telomere is sufficient to induce the
      recruitment of checkpoint and recombination proteins. Notably, a DNA damage
      response at eroded telomeres starts many generations before senescence and is
      characterized by the recruitment of Cdc13 (cell division cycle 13), replication
      protein A, DNA damage checkpoint proteins and the DNA repair protein Rad52 into a
      single focus. Moreover, we show that eroded telomeres, although remaining at the
      nuclear periphery, move to the nuclear pore complex. Our results link the DNA
      damage response at eroded telomeres to changes in subnuclear localization and
      suggest the existence of collapsed replication forks at eroded telomeres.

PMID- 19597488
TI  - Persistent DNA damage signalling triggers senescence-associated inflammatory
      cytokine secretion.
AB  - Cellular senescence suppresses cancer by stably arresting the proliferation of
      damaged cells. Paradoxically, senescent cells also secrete factors that alter
      tissue microenvironments. The pathways regulating this secretion are unknown. We
      show that damaged human cells develop persistent chromatin lesions bearing
      hallmarks of DNA double-strand breaks (DSBs), which initiate increased secretion
      of inflammatory cytokines such as interleukin-6 (IL-6). Cytokine secretion
      occurred only after establishment of persistent DNA damage signalling, usually
      associated with senescence, not after transient DNA damage responses (DDRs).
      Initiation and maintenance of this cytokine response required the DDR proteins
      ATM, NBS1 and CHK2, but not the cell-cycle arrest enforcers p53 and pRb. ATM was
      also essential for IL-6 secretion during oncogene-induced senescence and by
      damaged cells that bypass senescence. Furthermore, DDR activity and IL-6 were
      elevated in human cancers, and ATM-depletion suppressed the ability of senescent
      cells to stimulate IL-6-dependent cancer cell invasiveness. Thus, in addition to
      orchestrating cell-cycle checkpoints and DNA repair, a new and important role of
      the DDR is to allow damaged cells to communicate their compromised state to the
      surrounding tissue.

PMID- 19597489
TI  - Prolyl isomerase Pin1 acts as a switch to control the degree of substrate
      ubiquitylation.
AB  - Pin1, a conserved eukaryotic peptidyl-prolyl cis/trans isomerase, has important
      roles in cellular regulation. Because of its activity to switch the conformation
      of peptidyl-proline bonds in polypeptide chains, Pin1 operates as a binary
      switch, often in fate-determining pathways. Pin1 activity is usually controlled
      by substrate phosphorylation, but how Pin1 switches protein fates has been
      unclear. Here we show that Pin1 controls the degree of substrate ubiquitylation
      and thereby protein functions. We found that yeast Pin1 (Ess1) is essential for
      viability because it controls the NF-kappaB-related Spt23 transcription factor
      involved in unsaturated fatty-acid synthesis. High Pin1 activity results in low
      ubiquitylation of Spt23, which triggers Spt23 precursor processing and hence
      transcription factor activation. By contrast, decreased Pin1 activity leads to
      robust Spt23 polyubiquitylation and subsequent proteasomal degradation.
      Inhibition of Pin1 in mammalian cells changes the ubiquitylation status of the
      tumour suppressor protein p53 from oligoubiquitylation, which is known to trigger
      nuclear export, to polyubiquitylation, which causes nuclear p53 degradation. This
      suggests that the Pin1 activity is often translated into a fate-determining
      ubiquitylation switch, and that Pin1 may affect the degree of substrate
      ubiquitylation in other pathways as well.

PMID- 19597490
TI  - A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated
      epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is
      triggered during carcinoma progression to an invasive state. Transforming growth
      factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt,
      to induce EMT, but the molecular mechanisms are not clear. Here, we report that
      SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional
      repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the
      gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta
      driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors
      of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells.
      Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR
      and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with
      nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma
      and at the invasive fronts of human breast cancer. We propose that activation of
      a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene
      repression during EMT.

PMID- 19597491
TI  - A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and
      ischemic stroke.
AB  - We expanded our genome-wide association study on atrial fibrillation (AF) in
      Iceland, which previously identified risk variants on 4q25, and tested the most
      significant associations in samples from Iceland, Norway and the United States. A
      variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated
      significantly with AF (odds ratio OR = 1.21, P = 1.4 x 10(-10)). This variant
      also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic
      stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.

PMID- 19597493
TI  - De novo copy number variants identify new genes and loci in isolated sporadic
      tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF), the most common severe congenital heart malformation,
      occurs sporadically, without other anomaly, and from unknown cause in 70% of
      cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected
      parents, we identified 11 de novo copy number variants (CNVs) that were absent or
      extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent
      TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at
      chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic
      TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs
      in a single subject with TOF occurred at six loci, two that encode known (NOTCH1,
      JAG1) disease-associated genes. Our findings predict that at least 10% (4.5
      15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de
      novo CNVs and suggest that mutations within these loci might be etiologic in
      other cases of TOF.

PMID- 19597492
TI  - Variants in ZFHX3 are associated with atrial fibrillation in individuals of
      European ancestry.
AB  - We conducted meta-analyses of genome-wide association studies for atrial
      fibrillation (AF) in participants from five community-based cohorts. Meta
      analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337
      referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio
      RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent
      cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined
      RR = 1.25; combined P = 1.8 x 10(-15)).

PMID- 19597494
TI  - Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations
      in the NAc.
AB  - Addictive drugs hijack mechanisms of learning and memory that normally underlie
      reinforcement of natural rewards and induce synaptic plasticity of glutamatergic
      transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental
      area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor
      dependent synaptic plasticity in DA neurons, whereas plasticity in the nucleus
      accumbens (NAc) occurs only after repeated injections. Whether these two forms of
      plasticity are independent or hierarchically organized remains unknown. We
      combined ex vivo electrophysiology in acute brain slices with behavioral assays
      modeling drug relapse in mice and found that the duration of the cocaine-evoked
      synaptic plasticity in the VTA is gated by mGluR1. Overriding mGluR1 in vivo made
      the potentiation in the VTA persistent. This led to synaptic plasticity in the
      NAc, which contributes to cocaine-seeking behavior after protracted withdrawal.
      Impaired mGluR1 function in vulnerable individuals could represent a first step
      in the recruitment of the neuronal network that underlies drug addiction.

PMID- 19597495
TI  - Sensory transformations and the use of multiple reference frames for reach
      planning.
AB  - The sensory signals that drive movement planning arrive in a variety of
      'reference frames', and integrating or comparing them requires sensory
      transformations. We propose a model in which the statistical properties of
      sensory signals and their transformations determine how these signals are used.
      This model incorporates the patterns of gaze-dependent errors that we found in
      our human psychophysics experiment when the sensory signals available for reach
      planning were varied. These results challenge the widely held ideas that error
      patterns directly reflect the reference frame of the underlying neural
      representation and that it is preferable to use a single common reference frame
      for movement planning. We found that gaze-dependent error patterns, often cited
      as evidence for retinotopic reach planning, can be explained by a transformation
      bias and are not exclusively linked to retinotopic representations. Furthermore,
      the presence of multiple reference frames allows for optimal use of available
      sensory information and explains task-dependent reweighting of sensory signals.

PMID- 19597496
TI  - A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in
      Mycobacterium tuberculosis-induced macrophage apoptosis.
AB  - Apoptosis is central to the interaction between pathogenic mycobacteria and host
      macrophages. Caspase-8-dependent apoptosis of infected macrophages, which
      requires activation of the mitogen-activated protein (MAP) kinase p38, lowers the
      spread of mycobacteria. Here we establish a link between the release of tumor
      necrosis factor (TNF) and mycobacteria-mediated macrophage apoptosis. TNF
      activated a pathway involving the kinases ASK1, p38 and c-Abl. This pathway led
      to phosphorylation of FLIP(S), which facilitated its interaction with the E3
      ubiquitin ligase c-Cbl. This interaction triggered proteasomal degradation of
      FLIP(S), which promoted activation of caspase-8 and apoptosis. Our findings
      identify a previously unappreciated signaling pathway needed for Mycobacterium
      tuberculosis-triggered macrophage cell death.

PMID- 19597497
TI  - Themis is a member of a new metazoan gene family and is required for the
      completion of thymocyte positive selection.
AB  - T cell antigen receptor (TCR) signaling in CD4(+)CD8(+) double-positive
      thymocytes determines cell survival and lineage commitment, but the genetic and
      molecular basis of this process is poorly defined. To address this issue, we used
      ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific
      gene, Themis, which is critical for the completion of positive selection. Themis
      contains a tandem repeat of a unique globular domain (called 'CABIT' here) that
      includes a cysteine motif that defines a family of five uncharacterized
      vertebrate proteins with orthologs in most animal species. Themis-deficient
      thymocytes showed no substantial impairment in early TCR signaling but did show
      altered expression of genes involved in the cell cycle and survival before and
      during positive selection. Our data suggest a unique function for Themis in
      sustaining positive selection.

PMID- 19597498
TI  - Themis, a T cell-specific protein important for late thymocyte development.
AB  - During positive selection, thymocytes transition through a stage during which T
      cell antigen receptor (TCR) signaling controls CD4-versus-CD8 lineage 'choice'
      and subsequent maturation. Here we describe a previously unknown T cell-specific
      protein, Themis, that serves a distinct function during this stage. In Themis(-/
      ) mice, thymocyte selection was impaired and the number of transitional
      CD4(+)CD8(int) thymocytes as well as CD4(+) or CD8(+) single-positive thymocytes
      was lower. Notably, although we detected no overt TCR-proximal signaling
      deficiencies, Themis(-/-) CD4(+)CD8(int) thymocytes showed developmental defects
      consistent with attenuated signaling that were reversible by TCR stimulation. Our
      results identify Themis as a critical component of the T cell developmental
      program and suggest that Themis functions to sustain and/or integrate signals
      required for proper lineage commitment and maturation.

PMID- 19597500
TI  - A general phase-transfer protocol for metal ions and its application in
      nanocrystal synthesis.
AB  - Nanocrystals prepared in organic media can be easily self-assembled into close
      packed hexagonal monolayers on solvent evaporation for various applications.
      However, they usually rely on the use of organometallic precursors that are
      soluble in organic solvents. Herein we report a general protocol to transfer
      metal ions from an aqueous solution to an organic medium, which involves mixing
      the aqueous solution of metal ions with an ethanolic solution of dodecylamine
      (DDA), and extracting the coordinating compounds formed between the metal ions
      and DDA into toluene. This approach could be applied towards transferring a wide
      variety of transition-metal ions with an efficiency of >95%, and enables the
      synthesis of a variety of metallic and semiconductor nanocrystals to be carried
      out in an organic medium using relatively inexpensive water-soluble metal salts
      as starting materials. This protocol could be easily extended to synthesize a
      variety of heterogeneous semiconductor/noble-metal hybrids and to nanocomposites
      with multiple functionalities.

PMID- 19597499
TI  - Themis controls thymocyte selection through regulation of T cell antigen receptor
      mediated signaling.
AB  - Themis (thymocyte-expressed molecule involved in selection), a member of a family
      of proteins with unknown functions, is highly conserved among vertebrates. Here
      we found that Themis had high expression in thymocytes between the pre-T cell
      antigen receptor (pre-TCR) and positive-selection checkpoints and low expression
      in mature T cells. Themis-deficient thymocytes showed defective positive
      selection, which resulted in fewer mature thymocytes. Negative selection was also
      impaired in Themis-deficient mice. A greater percentage of Themis-deficient T
      cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory
      phenotypes than did wild-type T cells. In support of the idea that Themis is
      involved in TCR signaling, this protein was phosphorylated quickly after TCR
      stimulation and was needed for optimal TCR-driven calcium mobilization and
      activation of the kinase Erk.

PMID- 19597501
TI  - Global discovery of adaptive mutations.
AB  - Although modern DNA sequencing enables rapid identification of genetic variation,
      characterizing the phenotypic consequences of individual mutations remains a
      labor-intensive task. Here we describe array-based discovery of adaptive
      mutations (ADAM), a technology that searches an entire bacterial genome for
      mutations that contribute to selectable phenotypic variation between an evolved
      strain and its parent. We found that ADAM identified adaptive mutations in
      laboratory-evolved Escherichia coli strains with high sensitivity and
      specificity.

PMID- 19597502
TI  - Dereplication and de novo sequencing of nonribosomal peptides.
AB  - Nonribosomal peptides (NRPs) are of great pharmacological importance, but there
      is currently no technology for high-throughput NRP 'dereplication' and
      sequencing. We used multistage mass spectrometry followed by spectral alignment
      algorithms for sequencing of cyclic NRPs. We also developed an algorithm for
      comparative NRP dereplication that establishes similarities between newly
      isolated and previously identified similar but nonidentical NRPs, substantially
      reducing dereplication efforts.

PMID- 19597503
TI  - Metabolic network analysis integrated with transcript verification for sequenced
      genomes.
AB  - With sequencing of thousands of organisms completed or in progress, there is a
      growing need to integrate gene prediction with metabolic network analysis. Using
      Chlamydomonas reinhardtii as a model, we describe a systems-level methodology
      bridging metabolic network reconstruction with experimental verification of
      enzyme encoding open reading frames. Our quantitative and predictive metabolic
      model and its associated cloned open reading frames provide useful resources for
      metabolic engineering.

PMID- 19597504
TI  - Imaging transforming growth factor-beta signaling dynamics and therapeutic
      response in breast cancer bone metastasis.
AB  - Although the transforming growth factor-beta (TGF-beta) pathway has been
      implicated in breast cancer metastasis, its in vivo dynamics and temporal-spatial
      involvement in organ-specific metastasis have not been investigated. Here we
      engineered a xenograft model system with a conditional control of the TGF-beta
      SMAD signaling pathway and a dual-luciferase reporter system for tracing both
      metastatic burden and TGF-beta signaling activity in vivo. Strong TGF-beta
      signaling in osteolytic bone lesions is suppressed directly by genetic and
      pharmacological disruption of the TGF-beta-SMAD pathway and indirectly by
      inhibition of osteoclast function with bisphosphonates. Notably, disruption of
      TGF-beta signaling early in metastasis can substantially reduce metastasis burden
      but becomes less effective when bone lesions are well established. Our in vivo
      system for real-time manipulation and detection of TGF-beta signaling provides a
      proof of principle for using similar strategies to analyze the in vivo dynamics
      of other metastasis-associated signaling pathways and will expedite the
      development and characterization of therapeutic agents.

PMID- 19597505
TI  - Sex differences in the Toll-like receptor-mediated response of plasmacytoid
      dendritic cells to HIV-1.
AB  - Manifestations of viral infections can differ between women and men, and marked
      sex differences have been described in the course of HIV-1 disease. HIV-1
      infected women tend to have lower viral loads early in HIV-1 infection but
      progress faster to AIDS for a given viral load than men. Here we show substantial
      sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1.
      pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in
      response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived
      from men, resulting in stronger secondary activation of CD8(+) T cells. In line
      with these in vitro studies, treatment-naive women chronically infected with HIV
      1 had considerably higher levels of CD8(+) T cell activation than men after
      adjusting for viral load. These data show that sex differences in TLR-mediated
      activation of pDCs may account for higher immune activation in women compared to
      men at a given HIV-1 viral load and provide a mechanism by which the same level
      of viral replication might result in faster HIV-1 disease progression in women
      compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a
      new approach to reduce HIV-1-associated pathology.

PMID- 19597506
TI  - Noninvasive optical imaging of apoptosis by caspase-targeted activity-based
      probes.
AB  - Imaging agents that enable direct visualization and quantification of apoptosis
      in vivo have great potential value for monitoring chemotherapeutic response as
      well as for early diagnosis and disease monitoring. We describe here the
      development of fluorescently labeled activity-based probes (ABPs) that covalently
      label active caspases in vivo. We used these probes to monitor apoptosis in the
      thymi of mice treated with dexamethasone as well as in tumor-bearing mice treated
      with the apoptosis-inducing monoclonal antibody Apomab (Genentech). Caspase ABPs
      provided direct readouts of the kinetics of apoptosis in live mice, whole organs
      and tissue extracts. The probes produced a maximum fluorescent signal that could
      be monitored noninvasively and that coincided with the peak in caspase activity,
      as measured by gel analysis. Overall, these studies demonstrate that caspase
      specific ABPs have the potential to be used for noninvasive imaging of apoptosis
      in both preclinical and clinical settings.

PMID- 19597507
TI  - A new glucagon and GLP-1 co-agonist eliminates obesity in rodents.
AB  - We report the efficacy of a new peptide with agonism at the glucagon and GLP-1
      receptors that has potent, sustained satiation-inducing and lipolytic effects.
      Selective chemical modification to glucagon resulted in a loss of specificity,
      with minimal change to inherent activity. The structural basis for the co-agonism
      appears to be a combination of local positional interactions and a change in
      secondary structure. Two co-agonist peptides differing from each other only in
      their level of glucagon receptor agonism were studied in rodent obesity models.
      Administration of PEGylated peptides once per week normalized adiposity and
      glucose tolerance in diet-induced obese mice. Reduction of body weight was
      achieved by a loss of body fat resulting from decreased food intake and increased
      energy expenditure. These preclinical studies indicate that when full GLP-1
      agonism is augmented with an appropriate degree of glucagon receptor activation,
      body fat reduction can be substantially enhanced without any overt adverse
      effects.

PMID- 19597508
TI  - Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast
      and animal models.
AB  - Phage display has demonstrated the utility of cyclic peptides as general protein
      ligands but cannot access proteins inside eukaryotic cells. Expanding a new
      chemical genetics tool, we describe the first expressed library of head-to-tail
      cyclic peptides in yeast (Saccharomyces cerevisiae). We applied the library to
      selections in a yeast model of alpha-synuclein toxicity that recapitulates much
      of the cellular pathology of Parkinson's disease. From a pool of 5 million
      transformants, we isolated two related cyclic peptide constructs that
      specifically reduced the toxicity of human alpha-synuclein. These expressed
      cyclic peptide constructs also prevented dopaminergic neuron loss in an
      established Caenorhabditis elegans Parkinson's model. This work highlights the
      speed and efficiency of using libraries of expressed cyclic peptides for forward
      chemical genetics in cellular models of human disease.

PMID- 19597509
TI  - Are RAS mutations predictive markers of resistance to standard chemotherapy?
AB  - KRAS mutations may be predictive of resistance to anti-EGFR monoclonal-based
      therapy in patients with colorectal cancer (CRC). Screening for KRAS mutations in
      patients with CRC and non-small-cell lung cancer (NSCLC) may provide additional
      information on optimizing treatment options with targeted therapies. Only limited
      studies, however, have assessed the predictive value of KRAS mutations in
      response to conventional chemotherapy. We reviewed all relevant papers
      investigating the association of KRAS mutations and conventional chemotherapy
      related outcome in NSCLC, CRC, and other solid tumors, both in the adjuvant and
      advanced settings. Our Review strongly suggests that KRAS mutations have no value
      in response prediction to conventional chemotherapy in NSCLC, CRC and other solid
      tumors. Therefore, KRAS mutations should not be used as molecular predictors of
      response to conventional chemotherapy.

PMID- 19597510
TI  - Endoscopy for upper gastrointestinal bleeding: how urgent is it?
AB  - Early endoscopy has been advocated for the management of upper gastrointestinal
      bleeding, but the optimal timing for early endoscopy is still uncertain. The aim
      of this Review is to evaluate the optimal timing of early endoscopy by examining
      the findings of randomized clinical trials and retrospective cohort studies that
      used comparable outcome measures and have been reported in the literature.
      Outcome measurements included recurrent bleeding, surgery, mortality, length of
      hospital stay, and blood transfusion. Studies were categorized into those in
      which endoscopy was performed within 2-3 h, 6-8 h, 12 h or 24 h of the patient's
      presentation to hospital. We conclude that early endoscopy aids risk
      stratification of patients and reduces the need for hospitalization. However, it
      may also expose additional cases of active bleeding and hence increase the use of
      therapeutic endoscopy. No evidence exists that very early endoscopy (within a few
      hours of presentation) can reduce the risk of rebleeding or improve survival.

PMID- 19597511
TI  - Sensors of the innate immune system: their mode of action.
AB  - The discovery of molecular sensors that enable eukaryotes to recognize microbial
      pathogens and their products has been a key advance in our understanding of
      innate immunity. A tripartite sensing apparatus has developed to detect danger
      signals from infectious agents and damaged tissues, resulting in an immediate but
      short-lived defense response. This apparatus includes Toll-like receptors,
      retinoid acid-inducible gene-I-like receptors and other cytosolic nucleic acid
      sensors, and nucleotide-binding and oligomerization domain-like receptors;
      adaptors, kinases and other signaling molecules are required to elicit effective
      responses. Although this sensing is beneficial to the host, excessive activation
      and/or engagement by self molecules might induce autoimmune and other
      inflammatory disorders.

PMID- 19597512
TI  - Ureteral stent symptoms and associated infections: a biomaterials perspective.
AB  - Ureteral stents are commonly used in the field of urology, and, given their
      indwelling nature, are often a nidus for infection and a cause of discomfort. To
      minimize symptoms, the urologic surgeon should first consider whether a stent
      needs to be placed at all. Softer stents do not seem to improve patient comfort.
      Stents that are too long, specifically those that cross the midline of the
      bladder, significantly increase the frequency of stent-related symptoms.
      Administering alpha blockers while the stent is indwelling can reduce these
      symptoms. Antibiotic prophylaxis or concomitant antibiotic administration does
      not seem to reduce the incidence of stent-related urinary tract infection. At
      present, drug-eluting stents have shown the most promise for inhibiting bacterial
      adhesion and biofilm formation. Future stent designs that maintain drainage of
      the kidney and ureter while minimizing inflammation and contact with the
      urothelium will improve patient outcomes. By better understanding the basic
      pathways of bacterial adhesion to biomaterials, new stents and medications that
      target these mechanisms can be developed to eliminate bacterial adhesion and
      infection in patients with ureteral stents.

PMID- 19597513
TI  - A guide to disorders causing transient loss of consciousness: focus on syncope.
AB  - Episodes of transient loss of consciousness (TLOC) events pose diagnostic
      difficulties, as the causes are diverse, carry vastly different risks, and span
      various specialties. An inconsistent terminology contributes to the confusion.
      Here, we present a classification scheme for TLOC, based on ongoing
      multidisciplinary efforts including those of the Task Force on Syncope of the
      European Society of Cardiology. We also discuss the pathophysiology of TLOC and
      the key clinical features that aid diagnosis. TLOC is defined as an apparent loss
      of consciousness with an abrupt onset, a short duration, and a spontaneous and
      complete recovery. Syncope is defined as TLOC due to cerebral hypoperfusion, and
      is divided into reflex syncope (synonymous with neurally mediated syncope),
      syncope due to orthostatic hypotension, and cardiac syncope (arrhythmic or
      associated with structural cardiac disease). The other major groups of TLOC are
      generalized epileptic seizures, functional TLOC (psychogenic TLOC mimicking
      either epilepsy or syncope), and a further group of miscellaneous disorders. The
      management of patients who experience TLOC requires the recognition of the
      defining features of each of the major groups, and cooperation between different
      clinical specialties.

PMID- 19597515
TI  - Migraine during pregnancy: is it more than a headache?
AB  - Migraine headaches have a female predominance with a peak in prevalence in the
      third and fourth decades of life. Women of reproductive age are liable to develop
      their first migraine while pregnant or exhibit changes in the character,
      frequency or severity of their headaches during pregnancy and the puerperium. The
      purpose of this Review is to examine the pathophysiology underlying the
      development of migraine headaches and the association of this pathophysiology
      with pregnancy-related complications. We also discuss the diagnosis and
      management of migraine headaches that precede pregnancy or develop de novo during
      pregnancy, placing an emphasis on the distinction between primary migraine
      headache and headache secondary to pre-eclampsia--a relatively frequent
      complication of pregnancy and the puerperium. We present the case of a woman with
      a history of migraine headaches before pregnancy, whose symptoms progressed
      during pregnancy in part because of increasing exposure to narcotic medications.
      We also review the options for migraine evaluation and treatment, and provide an
      overview of the risks associated with the different treatment options.

PMID- 19597516
TI  - Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of
      action and unanswered questions.
AB  - Rimonabant and taranabant are two extensively studied cannabinoid-1 receptor
      (CB1R) inverse agonists. Their effects on in vivo peripheral tissue metabolism
      are generally well replicated. The central nervous system site of action of
      taranabant or rimonabant is firmly established based on brain receptor occupancy
      studies. At the whole-body level, the mechanism of action of CB1R inverse
      agonists includes a reduction in food intake and an increase in energy
      expenditure. At the tissue level, fat mass reduction, liver lipid reduction and
      improved insulin sensitivity have been shown. These effects on tissue metabolism
      are readily explained by CB1R inverse agonist acting on brain CB1R and indirectly
      influencing the tissue metabolism through the autonomic nervous system. It has
      also been hypothesized that rimonabant acts directly on adipocytes, hepatocytes,
      pancreatic islets or skeletal muscle in addition to acting on brain CB1R,
      although strong support for the contribution of peripherally located CB1R to in
      vivo efficacy is still lacking. This review will carefully examine the published
      literature and provide a perspective on what new tools and studies are required
      to address the peripheral site of action hypothesis.

PMID- 19597514
TI  - Advances in the genetics of glioblastoma: are we reaching critical mass?
AB  - Glioblastoma is the most common and highest-grade brain tumor, causing over
      10,000 deaths each year in the US alone. Given the resistance of this tumor to
      standard surgery, radiation and chemotherapy, an understanding of the underlying
      genetic lesions is vital. Recent efforts to comprehensively profile glioblastomas
      using the latest technologies, both by The Cancer Genome Atlas (TCGA) project and
      by other groups, are addressing this need. Some genetic aberrations in
      glioblastoma have been known for decades, but early output from the new profiling
      initiatives has further illuminated the relevant genetics in this disease. Some
      genetic lesions, such as TP53 mutation, NF1 deletion or mutation, and ERBB2
      amplification, have been found to be more common than was previously reported.
      New and unexpected discoveries have also been made, such as frequent mutations of
      the IDH1 and IDH2 genes in secondary glioblastoma. We might be tempted to
      speculate that we are approaching a comprehensive knowledge of the genetic
      lesions involved in glioblastoma, although other major discoveries doubtless
      remain to be made. In addition, the complex task of incorporating our updated
      knowledge into new--and possibly personalized--therapies for patients with
      glioblastoma still lies ahead.

PMID- 19597519
TI  - The effects of green tea on weight loss and weight maintenance: a meta-analysis.
AB  - INTRODUCTION: Different outcomes of the effect of green tea on weight loss (WL)
      and weight maintenance (WM) have been reported in studies with subjects differing
      in ethnicity and habitual caffeine intake. PURPOSE: To elucidate by meta-analysis
      whether green tea indeed has a function in body weight regulation. METHODS:
      English-language studies about WL and WM after green tea supplementation were
      identified through PubMed and based on the references from retrieved articles.
      Out of the 49 studies initially identified, a total of 11 articles fitted the
      inclusion criteria and provided useful information for the meta-analysis. Effect
      sizes (mean weight change in treatment versus control group) were computed and
      aggregated based on a random-effects model. The influence of several moderators
      on the effect sizes was examined. RESULTS: Catechins significantly decreased body
      weight and significantly maintained body weight after a period of WL (microcirc=
      1.31 kg; P<0.001). Inhibition of this effect by high habitual caffeine intake
      (>300 mg per day) failed to reach significance (microcirc=-0.27 kg for high and
      microcirc=-1.60 kg for low habitual caffeine intake; P=0.09). Also, the seemingly
      smaller effect of catechins in Caucasian (microcirc=-0.82 kg) subjects compared
      with Asians (microcirc=-1.51 kg; P=0.37) did not reach significance. Interaction
      of ethnicity and caffeine intake was a significant moderator (P=0.04).
      CONCLUSIONS: Catechins or an epigallocatechin gallate (EGCG)-caffeine mixture
      have a small positive effect on WL and WM. The results suggest that habitual
      caffeine intake and ethnicity may be moderators, as they may influence the effect
      of catechins.

PMID- 19597517
TI  - Expression profile of mRNAs encoding core circadian regulatory proteins in human
      subcutaneous adipose tissue: correlation with age and body mass index.
AB  - OBJECTIVE: Circadian mechanisms underlie the physiology of mammals as an
      adaptation to the earth's rotation on its axis. Highly conserved core circadian
      regulatory proteins (CCRPs) maintain an oscillatory expression profile in the
      central and peripheral tissues. The CCRP include both a positive and negative
      arm, as well as downstream transcriptional regulators. Recent studies in murine
      models have determined that the mRNAs encoding the CCRP are present in multiple
      adipose tissue depots and exhibit a robust oscillatory expression profile. This
      study set out to examine the expression of CCRP mRNAs in human subcutaneous
      adipose tissues. DESIGN: Retrospective analysis of total RNA isolated from
      subcutaneous adipose tissue. SUBJECTS: A total of 150 healthy female and male
      lean (body mass index (BMI) <25), overweight (BMI between 25 and 29.99) or obese
      (BMI >30) subjects of varied ethnic backgrounds undergoing elective liposuction
      or surgical procedures. RESULTS: The expression of the CCRP mRNAs displayed a
      significant correlation between each other and mRNAs representative of adipogenic
      biomarkers. Hierarchical cluster analyses of mRNAs isolated from the cohort of
      female Caucasian subjects (n=116) identified three major clusters based on
      expression of downstream CCRP mRNAs. The mRNAs encoding D site of albumin
      promoter-binding protein (DBP), E4 promoter-binding protein 4 (E4BP4), PPARgamma
      coactivator-1beta (PGC-1beta) and Rev-erbalpha were negatively correlated with
      BMI in a lean cluster (n=66), positively correlated with BMI in a younger
      overweight/obese cluster (n=19), and not significantly correlated with BMI in an
      older, overweight/obese cluster (n=31). CONCLUSIONS: These data confirm and
      extend findings that link the CCRP and circadian mechanisms to the risk of
      obesity.

PMID- 19597520
TI  - Training unsupported sitting in people with chronic spinal cord injuries: a
      randomized controlled trial.
AB  - STUDY DESIGN: Randomized, assessor-blinded trial. OBJECTIVES: To evaluate the
      effectiveness of a 6-week task-specific training programme on the abilities of
      people with chronic spinal cord injuries to sit unsupported. SETTING: NSW,
      Australia. METHODS: Thirty adults with spinal cord injuries of at least 1-year
      duration were recruited. Participants in the training group (n=15) performed up
      to 1 h of task-specific training three times a week for 6 weeks. Participants in
      the control group (n=15) did not receive any training or additional therapy.
      Primary outcome measures were the Canadian Occupational Performance Measure
      (COPM), and tests of Upper Body Sway, Maximal Balance Range and donning and
      doffing a T-shirt (the T-shirt test). RESULTS: The between-group mean difference
      (95% confidence interval) for the maximal balance range was 64 mm (95% confidence
      interval 20 to 108 mm; P=0.006). There were no significant between-group mean
      differences for the COPM and the Upper Body Sway and T-shirt tests. CONCLUSIONS:
      This trial shows initial support for intensive task-specific training for
      improving the abilities of people with chronic spinal cord injuries to sit
      unsupported, although the real-world implications of the observed treatment
      effects are yet to be determined.

PMID- 19597521
TI  - Life satisfaction, appraisals and functional outcomes in spinal cord-injured
      people living in the community.
AB  - STUDY DESIGN: Multi-centre, single cohort. OBJECTIVES: To assess the relationship
      between cognitive appraisals in a spinal cord-injured population living in the
      community, and examine how these factors affect social participation, life
      satisfaction and functional outcomes. SETTING: The National Spinal Injuries
      Centre, Stoke Mandeville, UK; Princess Royal Spinal Injuries Centre, Sheffield
      UK; Midlands Centre for Spinal Injuries, Oswestry, UK. METHOD: Participants
      (n=81) sustaining injury aged 18 or above were recruited from one of three spinal
      cord injuries units 3-18 months after discharge. Postal packs containing
      questionnaires, consent forms and information were distributed and a 2-week
      reminder sent. RESULTS: Participation was found to be strongly related to life
      satisfaction, negative appraisals of disability were found to explain 12.9% of
      the variance in total participation scores. The variance in scores on Life
      Satisfaction Questionnaires was explained by appraisals, participation and
      secondary complications to a total of 69.6%. Functional Independence Scores were
      explained by negative perceptions of disability, growth and resilience and total
      secondary complication scores, explaining 49.4% of the variance in this measure.
      CONCLUSION: Participation, functional independence and life satisfaction were
      significantly related to appraisal styles in this population. Negative
      perceptions of disability, fearful despondency and overwhelming disbelief were
      themes that impacted on the likelihood of participation and independence and
      involved in expressed levels of life satisfaction. Our results suggest the need
      to tackle cognitive styles of SCI patients before discharge to improve the
      rehabilitation process.

PMID- 19597522
TI  - A review of published reports on neuroprotection in spinal cord injury.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To review the main published current
      neuroprotection research trends and results in spinal cord injury (SCI). SETTING:
      This paper is the result of a collaboration between a group of European
      scientists. METHODS: Recent studies, especially in genetic, immune, histochemical
      and bio (nano)-technological fields, have provided new insight into the cellular
      and molecular mechanisms occurring within the central nervous system (NS),
      including SCIs. As a consequence, a new spectrum of therapies aiming to
      antagonize the 'secondary injury' pathways (that is, to provide neuroprotection)
      and also to repair such classically irreparable structures is emerging. We
      reviewed the most significant published works related to such novel, but not yet
      entirely validated, clinical practice therapies. RESULTS: There have been
      identified many molecules, primarily expressed by heterogenous glial and neural
      subpopulations of cells, which are directly or indirectly critical for tissue
      damaging/sparing/re-growth inhibiting, angiogenesis and neural plasticity, and
      also various substances/energy vectors with regenerative properties, such as MAG
      (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI
      (synthetic: Lysine-Asparagine-Isoleucine 'gamma-1 of Laminin Kainat Domain'),
      Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho
      signaling pathway (superfamily of 'Rho-dopsin gene-including neurotransmitter
      receptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different
      subtypes of serotonergic and glutamatergic receptors, antigens, antibodies,
      immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes,
      hormones, collagen scar inhibitors, remyelinating agents and
      neurogenetic/plasticity inducers, all aiming to preserve/re-establish the
      morphology and functional connections across the lesion site. Accordingly, modern
      research and experimental SCI therapies focus on several intricate, rather
      overlapping, therapeutic objectives and means, such as neuroprotective,
      neurotrophic, neurorestorative, neuroreparative, neuroregenerative,
      neuro(re)constructive and neurogenetic interventions. CONCLUSION: The first three
      of these therapeutical directions are generically assimilated as neuroprotective,
      and are synthetically presented and commented in this paper in an attempt to
      conceptually systematize them; thus, the aim of this article is, by emphasizing
      the state-of-the art in the domain, to optimize theoretical support in selecting
      the most effective pharmacological and physical interventions for preventing, as
      much as possible, paralysis, and for maximizing recovery chances after SCI.

PMID- 19597518
TI  - Association of objectively assessed physical activity with total and central body
      fat in Spanish adolescents; the HELENA Study.
AB  - OBJECTIVES: To examine the association of objectively assessed physical activity
      (PA) with markers of total and central body fat in adolescents, and to determine
      whether meeting the current PA recommendations (> or = 60 min day(-1) of at least
      moderate intensity PA) is associated with reduced levels of total and central
      body fat. SUBJECTS/METHODS: A total of 365 Spanish adolescents aged 12.5-17.5
      years participated in this cross-sectional study. PA was assessed by
      accelerometry and expressed as average PA (counts per minute), and min day(-1) of
      light, moderate, moderate to vigorous (MVPA) and vigorous PA. MVPA was
      dichotomized into < 60 min day(-1) and > or = 60. Total body fat was measured by
      DXA, BodPod and the sum of six skinfolds. Central body fat was measured by DXA at
      three regions (R1, R2 and R3), and waist circumference. RESULTS: All markers of
      central body fat were negatively associated with vigorous PA (P < 0.01) after
      controlling for sex, age and pubertal status. Abdominal adiposity measured at R1,
      R2 and R3 was also negatively associated with MVPA (P < or = 0.001), and with
      average PA (P < 0.01). All markers of total body fat were negatively associated
      with vigorous PA (P < 0.01), MVPA (P < 0.01) and average PA (P < 0.05).
      Adolescents engaged on at least 60 min day(-1) MVPA presented lower levels of
      total (P < 0.05) and central body fat (P < or = 0.01). CONCLUSIONS: The results
      suggest that vigorous PA may have a greater effect on preventing obesity in
      adolescents than does PA of lower intensity, whereas both average PA and at least
      moderate PA may have an impact on total and central body fat in youth.

PMID- 19597523
TI  - Discovery of potent inhibitors for phosphodiesterase 5 by virtual screening and
      pharmacophore analysis.
AB  - AIM: To explore the potent inhibitor from one of the Traditional Chinese medicine
      (TCM), Epimedium sagittatum. METHODS: We predicted the potent compound, ES03b, de
      novo evolution from the four Epimedium sagittatum components were verified by
      molecular docking, pharmacophore analysis, and analysis of quantitative structure
      activity relationship (QSAR) model, which was constructed by multiple linear
      regression. RESULTS: ES03b was chosen to undergo drug modification via de novo
      evolution. By analyzing the pharmacophore features, we found that the hydrophobic
      core in the binding site and the hydrogen bond generated at Asn663 played key
      roles in designing PDE5 inhibitors. ES03b generated 49 diversities (Evo01-49).
      Evo48 had high activity in prediction. Although the value of prediction was
      overestimated, Evo48 was suggested as the potent lead. CONCLUSION: In this study,
      we showed that the hydrophobic core in the binding site and hydrogen bond
      production on Asn663 played key roles to design PDE5 inhibitors. From several
      require validation analysis, Evo48 was suggested to be a potent inhibitor.

PMID- 19597524
TI  - Isoproterenol disperses distribution of NADPH oxidase, MMP-9, and pPKCepsilon in
      the heart, which are mitigated by endothelin receptor antagonist CPU0213.
AB  - AIM: Spatial dispersion of bioactive substances in the myocardium could serve as
      pathological basis for arrhythmogenesis and cardiac impairment by beta
      adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein
      kinase Cepsilon (PKCepsilon), early response gene (ERG), and matrix
      metalloproteinase 9(MMP-9) across the heart by isoproterenol (ISO) medication
      might be mediated by the endothelin (ET) - ROS pathway. We aimed to verify if ISO
      induced spatially heterogeneous distribution of pPKCepsilon, NAPDH oxidase, MMP-9
      and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS
      inhibitor aminoguanidine. METHODS: Rats were treated with ISO (1 mg/kg sc) for 10
      days, and drug interventions (mg/kg) either CPU0213 (30 sc) or aminoguanidine
      (100 ip) were administered on days 8-10. Expression of NADPH oxidase, MMP-9, ERG,
      and PKCepsilon in the left and right ventricle (LV, RV) and septum (S) were
      measured separately. RESULTS: Ventricular hypertrophy was found in the LV, S, and
      RV, in association with dispersed QTc and oxidative stress in ISO-treated rats.
      mRNA and protein expression of MMP-9, PKCepsilon, NADPH oxidase and ERG in the
      LV, S, and RV were obviously dispersed, with augmented expression mainly in the
      LV and S. Dispersed parameters were re-harmonized by either CPU0213, or
      aminoguanidine. CONCLUSION: We found at the first time that ISO-induced dispersed
      distribution of pPKCepsilon, NADPH oxidase, MMP-9, and ERG in the LV, S, and RV
      of the heart, which were suppressed by either CPU0213 or aminoguanidine. It
      indicates that the ET-ROS pathway plays a role in the dispersed distribution of
      bioactive substances following sustained beta-receptor stimulation.

PMID- 19597525
TI  - Protective effects of betaglucin on myocardial tissue during myocardial
      infarction in rats and dogs.
AB  - AIM: To test the protective effects of betaglucin, a novel beta-glucan, on models
      of myocardial infarction (MI) in rats and dogs. METHODS: The left anterior
      descending (LAD) coronary artery occlusion model was used to induce an MI in rats
      and dogs. Three doses of betaglucin (10, 30 and 100 mg/kg), propranolol (positive
      control, 1 mg/kg) and vehicle alone (5% glucose solution) were administered
      before LAD occlusion, and characteristics of the resulting MI were subsequently
      assessed. In anesthetized dogs, blood pressure, heart rate, ventricular function,
      coronary artery blood flow and myocardial oxygen consumption were determined
      before and after the drug administration. RESULTS: The MI mass in both rats and
      dogs was significantly reduced by betaglucin (30 and 100 mg/kg, P<0.01) and
      propranolol (P<0.01). In anesthetized dogs, coronary artery blood flow was
      increased significantly by betaglucin (30 and 100 mg/kg, P<0.01), but blood
      pressure, heart rate and ventricular function were not changed (P>0.05). High
      dose betaglucin (100 mg/kg) increased myocardial oxygen consumption, but not to a
      statistically significant level (P>0.05). The hemodynamic indexes were
      significantly changed by propranolol. CONCLUSION: Betaglucin has protective
      effects on myocardial tissue during MI in rats and dogs and has no influence on
      hemodynamic parameters at a therapeutic dose. The increase in coronary artery
      blood flow induced by betaglucin might be beneficial in the treatment of patients
      with MI.

PMID- 19597527
TI  - Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing
      IL-17 production and inhibits differentiation of Th17 cells.
AB  - AIM: The aim of this study was to determine the therapeutic effect of
      Periplocoside A (PSA), a natural product isolated from the traditional Chinese
      herbal medicine Periploca sepium Bge, in MOG(35-55) (myelin oligodendrocyte
      glycoprotein 35-55)-induced experimental autoimmune encephalomyelitis (EAE).
      METHODS: Female C57BL/6 mice immunized with MOG(35-55) were treated with (50
      mg/kg or 25 mg/kg) or without PSA following immunization and continuously
      throughout the study. The degree of CNS inflammation was evaluated by H&E
      staining. Anti-MOG-specific recall responses were analyzed by [3H]-Thymidine
      incorporation, ELISA, and RT-PCR. The proportion of IL-17-producing T cells was
      measured by flow cytometry. RESULTS: Oral administration of PSA significantly
      reduced the incidence and severity of EAE, which closely paralleled the
      inhibition of MOG(35-55)-specific IL-17 production. Importantly, PSA inhibited
      the transcription of IL-17 mRNA and RORgammat. Further studies examining
      intracellular staining and adoptive transfer EAE validated the direct suppressive
      effect of PSA on Th17 cells. In vitro studies also showed that PSA significantly
      inhibited the differentiation of Th17 cells from murine purified CD4+ T cells in
      a dose-dependent manner. CONCLUSION: PSA ameliorated EAE by suppressing IL-17
      production and inhibited the differentiation of Th17 cells in vitro. Our results
      provide new insight into the potential mechanisms underlying the
      immunosuppressive and anti-inflammatory effects of PSA.

PMID- 19597526
TI  - Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in
      diabetic rats via the PKC signaling pathway.
AB  - AIM: To investigate the influence of breviscapine on high glucose-induced
      hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo.
      METHODS: Cultured neonatal cardiomyocytes were divided into i) control; ii) high
      glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high
      glucose+breviscapine; or v) high glucose+NF-kappaB inhibitor BAY11-7082. Cellular
      contraction frequency and volumes were measured; the expression of protein kinase
      C (PKC), NF-kappaB, TNF-alpha, and c-fos were assessed by Western blot or reverse
      transcription-polymerase chain reaction (RT-PCR). Diabetic rats were induced by a
      single intraperitoneal injection of streptozotocin, and randomly divided into i)
      control rats; ii) diabetic rats; or iii) diabetic rats administered with
      breviscapine (10 or 25 mg x kg(-1) x d(-1)). After treatment with breviscapine
      for six weeks, the echocardiographic parameters were measured. All rats were then
      sacrificed and heart tissue was obtained for microscopy. The expression patterns
      of PKC, NF-kappaB, TNF-alpha, and c-fos were measured by Western blot or RT-PCR.
      RESULTS: Cardiomyocytes cultured in a high concentration of glucose showed an
      increased pulsatile frequency and cellular volume, as well as a higher expression
      of PKC, NF-kappaB, TNF-alpha, and c-fos compared with the control group.
      Breviscapine could partly prevent these changes. Diabetic rats showed relative
      cardiac hypertrophy and a higher expression of PKC, NF-kappaB, TNF-alpha, and c
      fos; treatment with breviscapine could ameliorate these changes in diabetic
      cardiomyopathy. CONCLUSION: Breviscapine prevented cardiac hypertrophy in
      diabetic rats by inhibiting the expression of PKC, which may have a protective
      effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-kappaB/c-fos
      signal transduction pathway.

PMID- 19597528
TI  - Effect of adrenotensin on cell proliferation is mediated by angiotensin II in
      cultured rat mesangial cells.
AB  - AIM: Both adrenomedullin (ADM) and adrenotensin (ADT) are derived from the same
      propeptide precursor, and both act as circulating hormones and local paracrine
      mediators with multiple biological activities. Compared with ADM, little is known
      about how ADT achieves its functions. In the present study, we investigated the
      effect of ADT on cell proliferation and transforming growth factor-beta (TGF
      beta) secretion in cultured renal mesangial cells (MCs) and determined whether
      angiotensin II (Ang II) was involved in mediating this process. METHODS: Cell
      proliferation was measured by bromodeoxyuridine (BrdU) incorporation assay, Ang
      II levels were assayed using an enzyme immunoassay, and real time PCR was used to
      measure Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor,
      angiotensinogen (AGT), renin, angiotensin converting enzyme (ACE) and TGF-beta1
      mRNA levels. TGF-beta1 and collagen type IV protein levels in cell media were
      measured using enzyme-linked immunoassays. RESULTS: ADT treatment induced cell
      proliferation in a concentration-dependent manner; it also increased the levels
      of TGF-beta1 mRNA and protein as well as collagen type IV excretion by cultured
      MCs. ADT treatment increased renin and AGT mRNAs as well as Ang II protein, but
      did not affect the ACE mRNA level. ADT up-regulated angiotensin AT1 receptor
      mRNA, but not that of the AT2 receptor. The angiotensin AT1 receptor antagonist
      losartan blocked the effects of ADT-induced cell proliferation, TGF-beta1 and
      collagen type IV synthesis and secretion. CONCLUSION: ADT has a stimulating role
      in cell proliferation in cultured MCs. Increases in the levels of Ang II and the
      AT1 receptor after ADT treatment mediate the stimulating effects of ADT on cell
      proliferation and extracellular matrix synthesis and secretion.

PMID- 19597529
TI  - All-trans retinoic acid potentiates the antibody response in mice to a
      lipopeptide antigen adjuvanted with liposomal lipid A.
AB  - Retinoic acid (RA), the bioactive metabolite of retinol, is essential for robust
      humoral immunity in animals and humans. Recent interest in RA as a vaccine
      adjuvant has been encouraged by reports showing cooperative enhancement of
      antibody responses to tetanus toxin in rodents by all-trans RA (ATRA) and a Toll
      like receptor-3 agonist. We hypothesized that RA would augment the antibody
      response to a co-delivered lipopeptide immunogen derived from the membrane
      proximal region (MPR) of HIV-1 gp41. The MPR is weakly immunogenic and could
      benefit from potent new humoral adjuvants. When co-formulated in liposomes and
      administered to BALB/C mice, ATRA alone did not elicit serum anti-peptide
      antibodies to an MPR-derived lipopeptide. However, addition of ATRA, but not 13
      cis RA, to a liposomal formulation containing the Toll-like receptor-4 agonist
      monophosphoryl lipid A resulted in a fourfold enhancement of serum anti-peptide
      IgG titers as compared with a formulation containing lipid A alone (P=0.00039).
      The difference did not arise from biophysical changes in the liposome
      formulation, including vesicle size, vesicle charge and liposome association of
      antigen. Thus, ATRA warrants further study as a vaccine adjuvant.

PMID- 19597531
TI  - Measuring therapeutic efficacy in the changing paradigm of castrate-resistant
      prostate cancer.
AB  - One of the current challenges in the evaluation of novel agents for the treatment
      of advanced prostate cancer is the identification of a surrogate end point for
      overall survival (OS). Prostate-specific antigen (PSA) levels have been used as a
      screening tool and a biomarker of response to both hormonal and cytotoxic agents.
      However, PSA levels do not seem to be a suitable surrogate end point for OS in
      trials of targeted agents for castrate-resistant prostate cancer (CRPC). These
      findings suggest the need for adopting measures of efficacy that more accurately
      reflect the mechanisms of action of these agents in phase II trials, in order to
      realize improvements in OS in the phase III setting. The Prostate Cancer Clinical
      Trials Working Group (PCWG2) have recently made recommendations for the design of
      future trials and advised that PSA levels should not be the sole criterion on
      which to base clinical decisions. Here, we appraise the end points that have been
      used in phase II and III trials in patients with CRPC, and highlight the need for
      the adoption of the PCWG2 guidelines, the recommendations of which include
      radiographic imaging, in addition to bone scintigraphy, and symptomatic or
      radiographic disease progression criteria.

PMID- 19597532
TI  - Isoflavone supplements stimulated the production of serum equol and decreased the
      serum dihydrotestosterone levels in healthy male volunteers.
AB  - The aim of this study was to evaluate the effect of supplementing healthy men
      with soy isoflavones on the serum levels of sex hormones implicated in prostate
      cancer development. A total of 28 Japanese healthy volunteers (18 equol producers
      and 10 equol non-producers) between 30 and 59 years of age were given soy
      isoflavones (60 mg daily) supplements for 3 months, and the changes in their sex
      hormone levels were investigated at the baseline and after administration. The
      serum and urine concentrations of daidzein, genistein, and the levels of equol in
      the fasting blood samples and 24-h stored urine samples were also measured. All
      28 volunteers completed the 3-month supplementation with isoflavone. No changes
      in the serum levels of estradiol and total testosterone were detected after 3
      month supplementation. The serum levels of sex hormone-binding globulin
      significantly increased, and the serum levels of free testosterone and
      dihydrotestosterone (DHT) decreased significantly after 3-month supplementation.
      Among the 10 equol non-producers, equol became detectable in the serum of two
      healthy volunteers after 3-month supplementation. This study revealed that short
      term administration of soy isoflavones stimulated the production of serum equol
      and decreased the serum DHT level in Japanese healthy volunteers. These results
      suggest the possibility of converting equol non-producers to producers by
      prolonged and consistent soy isoflavones consumption.

PMID- 19597533
TI  - Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects
      TMPRSS2-ERG fusion status.
AB  - TMPRSS2-ERG fusion is the most common oncogenic rearrangement in prostate cancer
      (CaP). Owing to this chromosomal rearrangement one TMPRSS2 allele loses its
      promoter, and one of the ETS-related gene (ERG) alleles gains that promoter
      leading to its overexpression in these tumor cells. Some studies suggest that
      TMPRSS2, an androgen-regulated type II transmembrane serine protease, may have an
      effect on CaP progression. We hypothesized that a difference in TMPRSS2
      expression may be present in vivo between CaP cells with and without TMPRSS2-ERG
      fusion, or a compensatory mechanism for the allelic loss of TMPRSS2 may balance
      that expression difference. Therefore, TMPRSS2 mRNA expression was evaluated in
      microdissected CaP cells with and without TMPRSS2-ERG fusion in 132 CaP patients
      and analyzed for its correlation with other androgen receptor (AR)-regulated
      genes and clinicopathological features. In vivo TMPRSS2 expression correlated
      with that of other AR-regulated genes, including PSA/KLK3 and PMEPA1, offering
      potential as AR surrogates. A significantly reduced expression of TMPRSS2 was
      evident in malignant cells harboring TMPRSS2-ERG fusion, but not in CaP cells
      without TMPRSS2-ERG fusion, further defining these two genetically distinct types
      of CaP.

PMID- 19597530
TI  - Mechanisms of change in gene copy number.
AB  - Deletions and duplications of chromosomal segments (copy number variants, CNVs)
      are a major source of variation between individual humans and are an underlying
      factor in human evolution and in many diseases, including mental illness,
      developmental disorders and cancer. CNVs form at a faster rate than other types
      of mutation, and seem to do so by similar mechanisms in bacteria, yeast and
      humans. Here we review current models of the mechanisms that cause copy number
      variation. Non-homologous end-joining mechanisms are well known, but recent
      models focus on perturbation of DNA replication and replication of non-contiguous
      DNA segments. For example, cellular stress might induce repair of broken
      replication forks to switch from high-fidelity homologous recombination to non
      homologous repair, thus promoting copy number change.

PMID- 19597534
TI  - From molecules and cells to diseases: West meets East for medical research in
      Tianjin.

PMID- 19597535
TI  - PrPC-related signal transduction is influenced by copper, membrane integrity and
      the alpha cleavage site.
AB  - The copper-binding, membrane-anchored, cellular prion protein (PrP(C)) has two
      constitutive cleavage sites producing distinct N- and C-terminal fragments (N1/C1
      and N2/C2). Using RK13 cells expressing either human PrP(C), mouse PrP(C) or
      mouse PrP(C) carrying the 3F4 epitope, this study explored the influence of the
      PrP(C) primary sequence on endoproteolytic cleavage and one putative PrP(C)
      function, MAP kinase signal transduction, in response to exogenous copper with or
      without a perturbed membrane environment. PrP(C) primary sequence, especially
      that around the N1/C1 cleavage site, appeared to influence basal levels of
      proteolysis at this location and extracellular signal-regulated kinase 1/2
      (ERK1/2) phosphorylation, with increased processing demonstrating an inverse
      relationship with basal ERK1/2 activation. Human PrP(C) showed increased N1/C1
      cleavage in response to copper alone, accompanied by specific p38 and JNK/SAPK
      phosphorylation. Combined exposure to copper plus the cholesterol-sequestering
      antibiotic filipin resulted in a mouse PrP(C)-specific substantial increase in
      signal protein phosphorylation, accompanied by an increase in N1/C1 cleavage.
      Mouse PrP(C) harboring the human N1/C1 cleavage site assumed more human-like
      profiles basally and in response to copper and altered membrane environments. Our
      results demonstrate that the PrP(C) primary sequence around the N1/C1 cleavage
      site influences endoproteolytic processing at this location, which appears linked
      to MAP kinase signal transduction both basally and in response to copper.
      Further, the primary sequence appears to confer a mutual dependence of N1/C1
      cleavage and membrane integrity on the fidelity of PrP(C)-related signal
      transduction in response to exogenous stimuli.

PMID- 19597536
TI  - Predicting intrinsic disorder in proteins: an overview.
AB  - The discovery of intrinsically disordered proteins (IDP) (i.e., biologically
      active proteins that do not possess stable secondary and/or tertiary structures)
      came as an unexpected surprise, as the existence of such proteins is in
      contradiction to the traditional "sequence-->structure-->function" paradigm.
      Accurate prediction of a protein's predisposition to be intrinsically disordered
      is a necessary prerequisite for the further understanding of principles and
      mechanisms of protein folding and function, and is a key for the elaboration of a
      new structural and functional hierarchy of proteins. Therefore, prediction of
      IDPs has attracted the attention of many researchers, and a number of prediction
      tools have been developed. Predictions of disorder, in turn, are playing major
      roles in directing laboratory experiments that are leading to the discovery of
      ever more disordered proteins, and thereby leading to a positive feedback loop in
      the investigation of these proteins. In this review of algorithms for intrinsic
      disorder prediction, the basic concepts of various prediction methods for IDPs
      are summarized, the strengths and shortcomings of many of the methods are
      analyzed, and the difficulties and directions of future development of IDP
      prediction techniques are discussed.

PMID- 19597537
TI  - Cost-effectiveness of interventions to promote physical activity: a modelling
      study.
AB  - BACKGROUND: Physical inactivity is a key risk factor for chronic disease, but a
      growing number of people are not achieving the recommended levels of physical
      activity necessary for good health. Australians are no exception; despite
      Australia's image as a sporting nation, with success at the elite level, the
      majority of Australians do not get enough physical activity. There are many
      options for intervention, from individually tailored advice, such as counselling
      from a general practitioner, to population-wide approaches, such as mass media
      campaigns, but the most cost-effective mix of interventions is unknown. In this
      study we evaluate the cost-effectiveness of interventions to promote physical
      activity. METHODS AND FINDINGS: From evidence of intervention efficacy in the
      physical activity literature and evaluation of the health sector costs of
      intervention and disease treatment, we model the cost impacts and health outcomes
      of six physical activity interventions, over the lifetime of the Australian
      population. We then determine cost-effectiveness of each intervention against
      current practice for physical activity intervention in Australia and derive the
      optimal pathway for implementation. Based on current evidence of intervention
      effectiveness, the intervention programs that encourage use of pedometers
      (Dominant) and mass media-based community campaigns (Dominant) are the most cost
      effective strategies to implement and are very likely to be cost-saving. The
      internet-based intervention program (AUS$3,000/DALY), the GP physical activity
      prescription program (AUS$12,000/DALY), and the program to encourage more active
      transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high
      probability of being under a AUS$50,000 per DALY threshold. GP referral to an
      exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if
      high time and travel costs for patients in screening and consulting an exercise
      physiologist are considered. CONCLUSIONS: Intervention to promote physical
      activity is recommended as a public health measure. Despite substantial
      variability in the quantity and quality of evidence on intervention
      effectiveness, and uncertainty about the long-term sustainability of behavioural
      changes, it is highly likely that as a package, all six interventions could lead
      to substantial improvement in population health at a cost saving to the health
      sector. Please see later in the article for Editors' Summary.

PMID- 19597538
TI  - Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating
      mechanism.
AB  - The acid-sensing ion channel 1 (ASIC1) is a key receptor for extracellular
      protons. Although numerous structural and functional studies have been performed
      on this channel, the structural dynamics underlying the gating mechanism remains
      unknown. We used normal mode analysis, mutagenesis, and electrophysiological
      methods to explore the relationship between the inherent dynamics of ASIC1 and
      its gating mechanism. Here we show that a series of collective motions among the
      domains and subdomains of ASIC1 correlate with its acid-sensing function. The
      normal mode analysis result reveals that the intrinsic rotation of the
      extracellular domain and the collective motions between the thumb and finger
      induced by proton binding drive the receptor to experience a deformation from the
      extracellular domain to the transmembrane domain, triggering the channel pore to
      undergo "twist-to-open" motions. The movements in the transmembrane domain
      indicate that the likely position of the channel gate is around Leu440. These
      motion modes are compatible with a wide body of our complementary mutations and
      electrophysiological data. This study provides the dynamic fundamentals of ASIC1
      gating.

PMID- 19597540
TI  - A 73-year-old man with long-term immobility presenting with abdominal pain.

PMID- 19597539
TI  - The role of anorexia in resistance and tolerance to infections in Drosophila.
AB  - Most infections induce anorexia but its function, if any, remains unclear.
      Because this response is common among animals, we hypothesized that infection
      induced diet restriction might be an adaptive trait that modulates the host's
      ability to fight infection. Two defense strategies protect hosts against
      infections: resistance, which is the ability to control pathogen levels, and
      tolerance, which helps the host endure infection-induced pathology. Here we show
      that infected fruit flies become anorexic and that diet restriction alters
      defenses, increasing the fly's tolerance to Salmonella typhimurium infections
      while decreasing resistance to Listeria monocytogenes. This suggests that
      attempts to extend lifespan through diet restriction or the manipulation of
      pathways mimicking this process will have complicated effects on a host's ability
      to fight infections.

PMID- 19597541
TI  - Drug discovery for schistosomiasis: hit and lead compounds identified in a
      library of known drugs by medium-throughput phenotypic screening.
AB  - BACKGROUND: Praziquantel (PZQ) is the only widely available drug to treat
      schistosomiasis. Given the potential for drug resistance, it is prudent to search
      for novel therapeutics. Identification of anti-schistosomal chemicals has
      traditionally relied on phenotypic (whole organism) screening with adult worms in
      vitro and/or animal models of disease-tools that limit automation and throughput
      with modern microtiter plate-formatted compound libraries. METHODS: A partially
      automated, three-component phenotypic screen workflow is presented that utilizes
      at its apex the schistosomular stage of the parasite adapted to a 96-well plate
      format with a throughput of 640 compounds per month. Hits that arise are
      subsequently screened in vitro against adult parasites and finally for efficacy
      in a murine model of disease. Two GO/NO GO criteria filters in the workflow
      prioritize hit compounds for tests in the animal disease model in accordance with
      a target drug profile that demands short-course oral therapy. The screen workflow
      was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of
      which 821 are drugs already approved for human use. This affords a unique
      starting point to 'reposition' (re-profile) drugs as anti-schistosomals with
      potential savings in development timelines and costs. FINDINGS: Multiple and
      dynamic phenotypes could be categorized for schistosomula and adults in vitro,
      and a diverse set of 'hit' drugs and chemistries were identified, including anti
      schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits
      prioritized for tests in the animal disease model, a number of leads were
      identified, one of which compares reasonably well with PZQ in significantly
      decreasing worm and egg burdens, and disease-associated pathology. Data arising
      from the three components of the screen are posted online as a community
      resource. CONCLUSIONS: To accelerate the identification of novel anti
      schistosomals, we have developed a partially automated screen workflow that
      interfaces schistosomula with microtiter plate-formatted compound libraries. The
      workflow has identified various compounds and drugs as hits in vitro and leads,
      with the prescribed oral efficacy, in vivo. Efforts to improve throughput,
      automation, and rigor of the screening workflow are ongoing.

PMID- 19597542
TI  - The heme biosynthetic pathway of the obligate Wolbachia endosymbiont of Brugia
      malayi as a potential anti-filarial drug target.
AB  - BACKGROUND: Filarial parasites (e.g., Brugia malayi, Onchocerca volvulus, and
      Wuchereria bancrofti) are causative agents of lymphatic filariasis and
      onchocerciasis, which are among the most disabling of neglected tropical
      diseases. There is an urgent need to develop macro-filaricidal drugs, as current
      anti-filarial chemotherapy (e.g., diethylcarbamazine [DEC], ivermectin and
      albendazole) can interrupt transmission predominantly by killing microfilariae
      (mf) larvae, but is less effective on adult worms, which can live for decades in
      the human host. All medically relevant human filarial parasites appear to contain
      an obligate endosymbiotic bacterium, Wolbachia. This alpha-proteobacterial
      mutualist has been recognized as a potential target for filarial nematode life
      cycle intervention, as antibiotic treatments of filarial worms harboring
      Wolbachia result in the loss of worm fertility and viability upon antibiotic
      treatments both in vitro and in vivo. Human trials have confirmed this approach,
      although the length of treatments, high doses required and medical counter
      indications for young children and pregnant women warrant the identification of
      additional anti-Wolbachia drugs. METHODS AND FINDINGS: Genome sequence analysis
      indicated that enzymes involved in heme biosynthesis might constitute a potential
      anti-Wolbachia target set. We tested different heme biosynthetic pathway
      inhibitors in ex vivo B. malayi viability assays and report a specific effect of
      N-methyl mesoporphyrin (NMMP), which targets ferrochelatase (FC, the last step).
      Our phylogenetic analysis indicates evolutionarily significant divergence between
      Wolbachia heme genes and their human homologues. We therefore undertook the
      cloning, overexpression and analysis of several enzymes of this pathway alongside
      their human homologues, and prepared proteins for drug targeting. In vitro enzyme
      assays revealed a approximately 600-fold difference in drug sensitivities to
      succinyl acetone (SA) between Wolbachia and human 5'-aminolevulinic acid
      dehydratase (ALAD, the second step). Similarly, Escherichia coli hemH (FC)
      deficient strains transformed with human and Wolbachia FC homologues showed
      significantly different sensitivities to NMMP. This approach enables functional
      complementation in E. coli heme deficient mutants as an alternative E. coli-based
      method for drug screening. CONCLUSIONS: Our studies indicate that the heme
      biosynthetic genes in the Wolbachia of B. malayi (wBm) might be essential for the
      filarial host survival. In addition, the results suggest they are likely
      candidate drug targets based upon significant differences in phylogenetic
      distance, biochemical properties and sensitivities to heme biosynthesis
      inhibitors, as compared to their human homologues.

PMID- 19597543
TI  - Interference with hemozoin formation represents an important mechanism of
      schistosomicidal action of antimalarial quinoline methanols.
AB  - BACKGROUND: The parasitic trematode Schistosoma mansoni is one of the major
      causative agents of human schistosomiasis, which afflicts 200 million people
      worldwide. Praziquantel remains the main drug used for schistosomiasis treatment,
      and reliance on the single therapy has been prompting the search for new
      therapeutic compounds against this disease. Our group has demonstrated that heme
      crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme
      detoxification route with lipid droplets involved in this process and acting as a
      potential chemotherapeutical target. In the present work, we investigated the
      effects of three antimalarial compounds, quinine (QN), quinidine (QND) and
      quinacrine (QCR) in a murine schistosomiasis model by using a combination of
      biochemical, cell biology and molecular biology approaches. METHODOLOGY/PRINCIPAL
      FINDINGS: Treatment of S. mansoni-infected female Swiss mice with daily
      intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11(th) to
      17(th) day after infection caused significant decreases in worm burden (39%-61%)
      and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%)
      in female worms recovered from QN- and QND-treated mice and correlated with
      reduction in the female worm burden. We also observed that QN treatment promoted
      remarkable ultrastructural changes in male and female worms, particularly in the
      gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in
      the liver. Microarray gene expression analysis indicated that QN treatment
      increased the expression of transcripts related to musculature, protein synthesis
      and repair mechanisms. CONCLUSIONS: The overall significant reduction in several
      disease burden parameters by the antimalarial quinoline methanols indicates that
      interference with Hz formation in S. mansoni represents an important mechanism of
      schistosomicidal action of these compounds and points out the heme
      crystallization process as a valid chemotherapeutic target to treat
      schistosomiasis.

PMID- 19597545
TI  - New Information about Albert Einstein's Brain.
AB  - In order to glean information about hominin (or other) brains that no longer
      exist, details of external neuroanatomy that are reproduced on endocranial casts
      (endocasts) from fossilized braincases may be described and interpreted. Despite
      being, of necessity, speculative, such studies can be very informative when
      conducted in light of the literature on comparative neuroanatomy, paleontology,
      and functional imaging studies. Albert Einstein's brain no longer exists in an
      intact state, but there are photographs of it in various views. Applying
      techniques developed from paleoanthropology, previously unrecognized details of
      external neuroanatomy are identified on these photographs. This information
      should be of interest to paleoneurologists, comparative neuroanatomists,
      historians of science, and cognitive neuroscientists. The new identifications of
      cortical features should also be archived for future scholars who will have
      access to additional information from improved functional imaging technology.
      Meanwhile, to the extent possible, Einstein's cerebral cortex is investigated in
      light of available data about variation in human sulcal patterns. Although much
      of his cortical surface was unremarkable, regions in and near Einstein's primary
      somatosensory and motor cortices were unusual. It is possible that these atypical
      aspects of Einstein's cerebral cortex were related to the difficulty with which
      he acquired language, his preference for thinking in sensory impressions
      including visual images rather than words, and his early training on the violin.

PMID- 19597544
TI  - Local suppression of T cell responses by arginase-induced L-arginine depletion in
      nonhealing leishmaniasis.
AB  - The balance between T helper (Th) 1 and Th2 cell responses is a major determinant
      of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses
      are not sufficient to account for healing or nonhealing. Here we show that high
      arginase activity, a hallmark of nonhealing disease, is primarily expressed
      locally at the site of pathology. The high arginase activity causes local
      depletion of L-arginine, which impairs the capacity of T cells in the lesion to
      proliferate and to produce interferon-gamma, while T cells in the local draining
      lymph nodes respond normally. Healing, induced by chemotherapy, resulted in
      control of arginase activity and reversal of local immunosuppression. Moreover,
      competitive inhibition of arginase as well as supplementation with L-arginine
      restored T cell effector functions and reduced pathology and parasite growth at
      the site of lesions. These results demonstrate that in nonhealing leishmaniasis,
      arginase-induced L-arginine depletion results in impaired T cell responses. Our
      results identify a novel mechanism in leishmaniasis that contributes to the
      failure to heal persistent lesions and suggest new approaches to therapy.

PMID- 19597546
TI  - In-group and out-group membership mediates anterior cingulate activation to
      social exclusion.
AB  - FUNCTIONAL MAGNETIC RESONANCE IMAGING WAS EMPLOYED TO EXAMINE SENSITIVITY TO
      SOCIAL EXCLUSION IN THREE CONDITIONS: same-race, other-race, and self-resembling
      faces. The anterior cingulate cortex (ACC), specifically the dorsal ACC, has been
      targeted as a key substrate in the physical and social pain matrix and was
      hypothesized to regulate activation response to various facial conditions. We
      show that participants demonstrated greatest ACC activation when being excluded
      by self-resembling and same-race faces, relative to other-race faces.
      Additionally, participants expressed greater distress and showed increased ACC
      activation as a result of exclusion in the same-race condition relative to the
      other-race condition. A positive correlation between implicit racial bias and
      activation in the amygdala was also evident. Implicit attitude about other-race
      faces partly explains levels of concern about exclusion by out-group individuals.
      These findings suggest that individuals are more distressed and their brain (i.e.
      neural alarm system) responds with greater activation when being excluded by
      individuals whom they are more likely to share group membership with.

PMID- 19597547
TI  - Towards a neuroscience of love: olfaction, attention and a model of
      neurohypophysial hormone action.

PMID- 19597548
TI  - Assessment of yellow fever epidemic risk: an original multi-criteria modeling
      approach.
AB  - BACKGROUND: Yellow fever (YF) virtually disappeared in francophone West African
      countries as a result of YF mass vaccination campaigns carried out between 1940
      and 1953. However, because of the failure to continue mass vaccination campaigns,
      a resurgence of the deadly disease in many African countries began in the early
      1980s. We developed an original modeling approach to assess YF epidemic risk
      (vulnerability) and to prioritize the populations to be vaccinated. METHODS AND
      FINDINGS: We chose a two-step assessment of vulnerability at district level
      consisting of a quantitative and qualitative assessment per country. Quantitative
      assessment starts with data collection on six risk factors: five risk factors
      associated with "exposure" to virus/vector and one with "susceptibility" of a
      district to YF epidemics. The multiple correspondence analysis (MCA) modeling
      method was specifically adapted to reduce the five exposure variables to one
      aggregated exposure indicator. Health districts were then projected onto a two
      dimensional graph to define different levels of vulnerability. Districts are
      presented on risk maps for qualitative analysis in consensus groups, allowing the
      addition of factors, such as population migrations or vector density, that could
      not be included in MCA. The example of rural districts in Burkina Faso show five
      distinct clusters of risk profiles. Based on this assessment, 32 of 55 districts
      comprising over 7 million people were prioritized for preventive vaccination
      campaigns. CONCLUSION: This assessment of yellow fever epidemic risk at the
      district level includes MCA modeling and consensus group modification. MCA
      provides a standardized way to reduce complexity. It supports an informed public
      health decision-making process that empowers local stakeholders through the
      consensus group. This original approach can be applied to any disease with
      documented risk factors.

PMID- 19597549
TI  - Detection of cancer with serum miRNAs on an oligonucleotide microarray.
AB  - Micro RNAs (miRNAs) are a class of small, non-coding RNA species that play
      critical roles throughout cellular development and regulation. miRNA expression
      patterns taken from various tissue types often point to the cellular lineage of
      an individual tissue type, thereby being a more invariant hallmark of tissue
      type. Recent work has shown that these miRNA expression patterns can be used to
      classify tumor cells, and that this classification can be more accurate than the
      classification achieved by using messenger RNA gene expression patterns. One
      aspect of miRNA biogenesis that makes them particularly attractive as a biomarker
      is the fact that they are maintained in a protected state in serum and plasma,
      thus allowing the detection of miRNA expression patterns directly from serum.
      This study is focused on the evaluation of miRNA expression patterns in human
      serum for five types of human cancer, prostate, colon, ovarian, breast and lung,
      using a pan-human microRNA, high density microarray. This microarray platform
      enables the simultaneous analysis of all human microRNAs by either fluorescent or
      electrochemical signals, and can be easily redesigned to include newly identified
      miRNAs. We show that sufficient miRNAs are present in one milliliter of serum to
      detect miRNA expression patterns, without the need for amplification techniques.
      In addition, we are able to use these expression patterns to correctly
      discriminate between normal and cancer patient samples.

PMID- 19597550
TI  - Xeno-free defined conditions for culture of human embryonic stem cells, neural
      stem cells and dopaminergic neurons derived from them.
AB  - BACKGROUND: Human embryonic stem cells (hESCs) may provide an invaluable resource
      for regenerative medicine. To move hESCs towards the clinic it is important that
      cells with therapeutic potential be reproducibly generated under completely
      defined conditions. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a four-step
      scalable process that is readily transferable to a Good Manufacture Practice
      (GMP) facility for the production of functional dopaminergic neurons from hESCs
      for potential clinical uses. We show that each of the steps (propagation of ESC-
      >generation of neural stem cells (NSC)-->induction of dopaminergic precursors-
      >maturation of dopaminergic neurons) could utilize xeno-free defined media and
      substrate, and that cells could be stored at intermediate stages in the process
      without losing their functional ability. Neurons generated by this process
      expressed midbrain and A9 dopaminergic markers and could be transplanted at an
      appropriate time point in development to survive after transplant.
      CONCLUSIONS/SIGNIFICANCE: hESCs and NSCs can be maintained in xeno-free defined
      media for a prolonged period of time while retaining their ability to
      differentiate into authentic dopaminergic neurons. Our defined medium system
      provides a path to a scalable GMP-applicable process of generation of
      dopaminergic neurons from hESCs for therapeutic applications, and a ready source
      of large numbers of neurons for potential screening applications.

PMID- 19597551
TI  - Cellular contractility requires ubiquitin mediated proteolysis.
AB  - BACKGROUND: Cellular contractility, essential for cell movement and
      proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA
      dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II
      Light Chain (MLC) Ser19, thereby activating actomyosin contractions. Microtubules
      are upstream inhibitors of contractility and their depolymerization or depletion
      cause cells to contract by activating RhoA. How microtubule dynamics regulates
      RhoA remains, a major missing link in understanding contractility. PRINCIPAL
      FINDINGS: We observed that contractility is inhibited by microtubules not only,
      as previously reported, in adherent cells, but also in non-adhering interphase
      and mitotic cells. Strikingly we observed that contractility requires ubiquitin
      mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of
      proteolysis, ubiquitination and neddylation all led to complete cessation of
      contractility and considerably reduced MLC Ser19 phosphorylation. CONCLUSIONS:
      Our results imply that cells express a contractility inhibitor that is degraded
      by ubiquitin mediated proteolysis, either constitutively or in response to
      microtubule depolymerization. This degradation seems to depend on a Cullin-RING
      ubiquitin ligase and is required for cellular contractions.

PMID- 19597552
TI  - A novel and efficient gene transfer strategy reduces glial reactivity and
      improves neuronal survival and axonal growth in vitro.
AB  - BACKGROUND: The lack of axonal regeneration in the central nervous system is
      attributed among other factors to the formation of a glial scar. This cellular
      structure is mainly composed of reactive astrocytes that overexpress two
      intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and
      vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin
      were shown to be the substrate for increased neuronal plasticity. Moreover,
      double knockout mice lacking both GFAP and vimentin presented lower levels of
      glial reactivity in vivo, significant axonal regrowth and improved functional
      recovery in comparison with wild-type mice after spinal cord hemisection. From
      these results, our objective was to develop a novel therapeutic strategy for
      axonal regeneration, based on the targeted suppression of astroglial reactivity
      and scarring by lentiviral-mediated RNA-interference (RNAi). METHODS AND
      FINDINGS: In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv
      shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous
      GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes,
      the use of these vectors resulted in a specific, stable and highly significant
      decrease in the corresponding protein levels. In a second model -- scratched
      primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM,
      decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic
      coculture model, cortical neurons displayed higher survival rates and increased
      neurite growth when cultured with astrocytes in which GFAP and vimentin had been
      invalidated by lentiviral-mediated RNAi. CONCLUSIONS: Lentiviral-mediated
      knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for
      modulating reactive gliosis and monitoring neuron/glia interactions. Thus,
      manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a
      promising therapeutic strategy for increasing glial permissiveness and permitting
      axonal regeneration after central nervous system lesions.

PMID- 19597553
TI  - The structural dilemma of bulk polyethylene: an intermediary structure.
AB  - BACKGROUND: The Fourier space (reciprocal space) image of bulk polyethylene
      consists of lines superimposed on the coherent diffuse background. The mixed
      character of the image indicates the complex nature of these compounds. The
      inability in detecting full images of reciprocal space of polymeric substances
      without Compton radiation and the other undesirable diffuse scatterings has
      misled the structural analysis (structural characterisation) of these materials.
      PRINCIPAL FINDINGS: We propose the use of anomalous diffractometry where, it is
      possible to obtain a real image of reciprocal space without Compton radiation and
      other undesirable scatterings. By using classical diffractometry techniques this
      procedure is not possible. This methodology permitted us to obtain the "Direct
      Delta function", in the case of polycrystalline substances that was not
      previously detected. A new procedure was proposed to interpret the image of
      reciprocal space of bulk polyethylene. The results show the predominance of the
      geometry of local order determination compared to the crystal unit cell. The
      analysis of x-ray diffraction images illustrates that the elementary structural
      unit is a tetrahedron. This structural unit illustrates the atoms in the network
      scatter in a coherent diffuse manner. Moreover, the interference function derived
      from the coherent diffuse scattering dampens out quickly and the degree of
      randomness is superior to a liquid state. The radial distribution function
      derived from this interference function shows bond shortening in the tetrahedron
      configuration. It is this particular effect, which stabilises polyethylene.
      CONCLUSION: Here we show by anomalous diffractometry that the traditional concept
      of the two-phase or the crystal-defect model is an oversimplification of the
      complex reality. The exploitation of anomalous diffractometry has illustrated
      that polyethylene has an intermediate ordered structure.

PMID- 19597557
TI  - A stable enol from a 6-substituted benzanthrone and its unexpected behaviour
      under acidic conditions.
AB  - Treatment of benzanthrone (1) with biphenyl-2-yl lithium leads to the
      surprisingly stable enol 4, which is converted by dehydrogenation into the
      benzanthrone derivative 7. Under acidic conditions 4 isomerises to the spiro
      compound 11 and the bicyclo[4.3.1]decane derivative 12. Furthermore, the
      formation of 7 and the hydrogenated compound 13 is observed. A mechanism for the
      formation of the reaction products is proposed and supported by DFT calculations.

PMID- 19597554
TI  - In vivo colocalisation of oskar mRNA and trans-acting proteins revealed by
      quantitative imaging of the Drosophila oocyte.
AB  - Efficient mRNA transport in eukaryotes requires highly orchestrated relationships
      between nuclear and cytoplasmic proteins. For oskar mRNA, the Drosophila
      posterior determinant, these spatio-temporal requirements remain opaque during
      its multi-step transport process. By in vivo covisualization of oskar mRNA with
      Staufen, its putative trafficking protein, we find oskar mRNA to be present in
      particles distinct from Staufen for part of its transport. oskar mRNA stably
      associated with Staufen near the posterior pole. We observe oskar mRNA to
      oligomerize as hundreds of copies forming large particles which are necessary for
      its long range transport and localization. We show the formation of these
      particles occurs in the nurse cell nucleus in an Hrp48-dependent manner. We
      present a more refined model of oskar mRNA transport in the Drosophila oocyte.

PMID- 19597555
TI  - A comparative proteomic analysis of the simple amino acid repeat distributions in
      Plasmodia reveals lineage specific amino acid selection.
AB  - BACKGROUND: Microsatellites have been used extensively in the field of
      comparative genomics. By studying microsatellites in coding regions we have a
      simple model of how genotypic changes undergo selection as they are directly
      expressed in the phenotype as altered proteins. The simplest of these tandem
      repeats in coding regions are the tri-nucleotide repeats which produce a repeat
      of a single amino acid when translated into proteins. Tri-nucleotide repeats are
      often disease associated, and are also known to be unstable to both expansion and
      contraction. This makes them sensitive markers for studying proteome evolution,
      in closely related species. RESULTS: The evolutionary history of the family of
      malarial causing parasites Plasmodia is complex because of the life-cycle of the
      organism, where it interacts with a number of different hosts and goes through a
      series of tissue specific stages. This study shows that the divergence between
      the primate and rodent malarial parasites has resulted in a lineage specific
      change in the simple amino acid repeat distribution that is correlated to A-T
      content. The paper also shows that this altered use of amino acids in SAARs is
      consistent with the repeat distributions being under selective pressure.
      CONCLUSIONS: The study shows that simple amino acid repeat distributions can be
      used to group related species and to examine their phylogenetic relationships.
      This study also shows that an outgroup species with a similar A-T content can be
      distinguished based only on the amino acid usage in repeats, and suggest that
      this might be a useful feature for proteome clustering. The lineage specific use
      of amino acids in repeat regions suggests that comparative studies of SAAR
      distributions between proteomes gives an insight into the mechanisms of expansion
      and the selective pressures acting on the organism.

PMID- 19597558
TI  - Highly thermosensitive Ca dynamics in a HeLa cell through IP(3) receptors.
AB  - Intracellular Ca(2+) distribution and its dynamics are essential for various
      cellular functions. We show with single HeLa cells that a microscopic heat pulse
      induces Ca(2+) uptake into intracellular stores during heating and Ca(2+) release
      from them at the onset of recooling, and the overshoot of Ca(2+) release occurs
      above the critical value of a temperature change, which decreases from 1.5 to 0.2
      degrees C on increasing the experimental temperature from 22 to 37 degrees C.
      This highly thermosensitive Ca(2+) dynamics is probably attributable to the
      altered balance between Ca(2+) uptake by endoplasmic reticulum Ca(2+)-ATPases and
      Ca(2+) release via inositol 1,4,5-trisphosphate receptors. These results suggest
      that Ca(2+) signaling is extremely sensitive to temperature changes, especially
      around body temperature, in cells expressing inositol 1,4,5-trisphosphate
      receptors.

PMID- 19597556
TI  - Use of an EZ-Tn5-based random mutagenesis system to identify a novel toxin
      regulatory locus in Clostridium perfringens strain 13.
AB  - BACKGROUND: Although useful for probing bacterial pathogenesis and physiology,
      current random mutagenesis systems suffer limitations for studying the toxin
      producing bacterium Clostridium perfringens. METHODOLOGY/PRINCIPAL FINDINGS: An
      EZ-Tn5-based random mutagenesis approach was developed for use in C. perfringens.
      This mutagenesis system identified a new regulatory locus controlling toxin
      production by strain 13, a C. perfringens type A strain. The novel locus,
      encoding proteins with homology to the AgrB and AgrD components of the Agr quorum
      sensing system of Staphylococcus aureus and two hypothetical proteins, was found
      to regulate early production of both alpha toxin and perfringolysin O (PFO) by
      strain 13. PFO production by the strain 13 DeltaagrB mutant could be restored by
      genetic complementation or by physical complementation, i.e. by co-culture of the
      strain 13 DeltaagrB mutant with a pfoA mutant of either strain 13 or C.
      perfringens type C CN3685. A similar AgrB- and AgrD-encoding locus is
      identifiable in all sequenced C. perfringens strains, including type B, C, D, and
      E isolates, suggesting this regulatory locus contributes to toxin regulation by
      most C. perfringens strains. In strain 13, the agrB and agrD genes were found to
      be co-transcribed in an operon with two upstream genes encoding hypothetical
      proteins. CONCLUSIONS/SIGNIFICANCE: The new Tn5-based random mutagenesis system
      developed in this study is more efficient and random than previously reported C.
      perfringens random mutagenesis approaches. It allowed identification of a novel
      C. perfringens toxin regulatory locus with homology to the Agr system of S.
      aureus and which functions as expected of an Agr-like quorum sensing system.
      Since previous studies have shown that alpha toxin and perfringolysin O are
      responsible for strain 13-induced clostridial myonecrosis in the mouse model, the
      new agr regulatory locus may have importance for strain 13 virulence.

PMID- 19597559
TI  - Neuropathology of the Guillain-Mollaret Triangle (Dentato-Rubro-Olivary Network)
      in Sudden Unexplained Perinatal Death and SIDS.
AB  - The present study was undertaken to evaluate the possible alterations of the
      triangle of Guillain and Mollaret (G-Mt), a neuronal brainstem/cerebellum network
      (from the dentate nucleus to red nucleus and inferior olivary nucleus) already
      known for its involvement in the pathogenesis of the palatal myoclonus, in sudden
      unexplained perinatal and infant death. In 44 cases of perinatal and infant death
      victims, aged from 26 gestational weeks to 10 months of life, we investigated,
      besides the histological morphology of the three nuclei, the c-fos and apoptotic
      expression, as well as the possible effects elicited by maternal cigarette
      smoking.A significant increase of lesions (hypoplasia and/or increased c-fos and
      apoptotic neuronal immunopositivity) of the three nuclei was found in unexplained
      death victims, compared with age-matched controls. These alterations were related
      to maternal cigarette smoking habit.We postulated that the G-Mt is an important
      network involved in the pathogenesis of a wide spectrum of pathological
      manifestations and that maternal smoking during pregnancy can exert an adverse
      influence on this complex, even leading to sudden death in vulnerable periods of
      perinatal or infant development.

PMID- 19597560
TI  - Morning glory syndrome associated with posterior lenticonus.
AB  - The clinical features of the morning glory syndrome (MSG) are demonstrated in a
      12-year-old male patient with the posterior lenticonus in the left eye. This
      patient had retinal detachment in the left eye. A complete ocular examination was
      performed and the patient underwent a pars plana vitrectomy of the left eye. Slit
      lamp examination revealed the posterior lenticonus with the posterior subcapsular
      opacities in the left eye. The fundus showed the symptoms of MGS. The discs were
      pink and deeply excavated, surrounded by a ring of chorioretinal pigmentary
      disturbance. The retina has remained reattached for six months after surgery.
      Although most cases of MGS present with retinal and vitrea abnormalities, it may
      also occur in association with the lens anomalies, including the posterior
      lenticonus and subcapsular cataract. This association may be helpful to explore
      the pathogenesis of MGS.

PMID- 19597561
TI  - Myelination and isochronicity in neural networks.
AB  - Our brain contains a multiplicity of neuronal networks. In many of these,
      information sent from presynaptic neurons travels through a variety of pathways
      of different distances, yet arrives at the postsynaptic cells at the same time.
      Such isochronicity is achieved either by changes in the conduction velocity of
      axons or by lengthening the axonal path to compensate for fast conduction. To
      regulate the conduction velocity, a change in the extent of myelination has
      recently been proposed in thalamocortical and other pathways. This is in addition
      to a change in the axonal diameter, a previously identified, more accepted
      mechanism. Thus, myelination is not a simple means of insulation or acceleration
      of impulse conduction, but it is rather an exquisite way of actively regulating
      the timing of communication among various neuronal connections with different
      length.

PMID- 19597562
TI  - Eight different types of dopaminergic neurons innervate the Drosophila mushroom
      body neuropil: anatomical and physiological heterogeneity.
AB  - We examined tyrosine hydroxylase (TH-GAL4) expression and anti-TH
      immunoreactivity in the Drosophila protocerebrum and characterized single cell
      clones of the TH-GAL4 neurons. Eight clusters of putative dopaminergic neurons
      were characterized. Neurons in three of the clusters project to the mushroom body
      neuropil: PAM neurons project to the medial portion of the horizontal lobes; PPL1
      neurons project to the vertical lobes, the junction area, the heel and distal
      peduncle; and PPL2ab neurons project to the calyx. Five types of PPL1 neurons
      were discovered that innervate different zones of the mushroom body lobes.
      Functional imaging experiments showed that the dopaminergic processes in four of
      the zones differ in response properties to odor, electric shock, or following the
      pairing of odor and electric shock. These results indicate that distinct
      dopaminergic neurons define separate zones of the mushroom body lobes and are
      probably involved in different functions. Differences in functional response
      properties of these neurons suggest that they are involved in different
      behavioral processes.

PMID- 19597565
TI  - Energetics of (Dis)Assembly of the Ternary SNARE Complex.

PMID- 19597563
TI  - Climbing fiber signaling and cerebellar gain control.
AB  - The physiology of climbing fiber signals in cerebellar Purkinje cells has been
      studied since the early days of electrophysiology. Both the climbing fiber-evoked
      complex spike and the role of climbing fiber activity in the induction of long
      term depression (LTD) at parallel fiber-Purkinje cell synapses have become
      hallmark features of cerebellar physiology. However, the key role of climbing
      fiber signaling in cerebellar motor learning has been challenged by recent
      reports of forms of synaptic and non-synaptic plasticity in the cerebellar cortex
      that do not involve climbing fiber activity, but might well play a role in
      cerebellar learning. Moreover, cerebellar LTD does not seem to strictly require
      climbing fiber activity. These observations make it necessary to re-evaluate the
      role of climbing fiber signaling in cerebellar function. Here, we argue that
      climbing fiber signaling is about adjusting relative probabilities for the
      induction of LTD and long-term potentiation (LTP) at parallel fiber synapses.
      Complex spike-associated, dendritic calcium transients control postsynaptic LTD
      and LTP induction. High calcium transients, provided by complex spike activity,
      do not only favor postsynaptic LTD induction, but simultaneously trigger
      retrograde cannabinoid signaling, which blocks the induction of presynaptic LTP.
      Plasticity of the climbing fiber input itself provides additional means to fine
      tune complex spike associated calcium signaling and thus to adjust the gain of
      heterosynaptic climbing fiber control. In addition to dendritic calcium
      transients, climbing fiber activity leads to the release of the neuropeptide
      corticotropin-releasing factor (CRF), which facilitates LTD induction at both
      parallel fiber and climbing fiber synapses.

PMID- 19597566
TI  - A model for transient oxygen delivery in cerebral cortex.
AB  - Popular hemodynamic brain imaging methods, such as blood oxygen-level dependent
      functional magnetic resonance imaging (BOLD fMRI), would benefit from a detailed
      understanding of the mechanisms by which oxygen is delivered to the cortex in
      response to brief periods of neural activity. Tissue oxygen responses in visual
      cortex following brief visual stimulation exhibit rich dynamics, including an
      early decrease in oxygen concentration, a subsequent large increase in
      concentration, and substantial late-time oscillations ("ringing"). We introduce a
      model that explains the full time-course of these observations made by Thompson
      et al. (2003). The model treats oxygen transport with a set of differential
      equations that include a combination of flow and diffusion in a three-compartment
      (intravascular, extravascular, and intracellular) system. Blood flow in this
      system is modeled using the impulse response of a lumped linear system that
      includes an inertive element; this provides a simple biophysical mechanism for
      the ringing. The model system is solved numerically to produce excellent fits to
      measurements of tissue oxygen. The results give insight into the dynamics of
      cerebral oxygen transfer, and can serve as the starting point to understand BOLD
      fMRI measurements.

PMID- 19597567
TI  - Molecular analysis of CYP1B1 in Omani patients with primary congenital glaucoma:
      a pilot study.
AB  - PURPOSE: To screen cytochrome P4501B1 (CYP1B1) for causative mutations in Omani
      patients with a clinical diagnosis of primary congenital glaucoma (PCG) METHODS:
      Nine PCG families were recruited for the study. All patients underwent detailed
      clinical examinations to confirm the diagnosis of PCG. The families of index
      patients were also examined. Genealogical information was obtained by pedigree
      analysis. The primary candidate gene, CYP1B1, was amplified from genomic DNA,
      sequenced, and analyzed in patients to identify the disease-causing mutations.
      RESULTS: Eight of the nine PCG families were consanguineous (89%). Molecular
      analysis of CYP1B1 showed three distinct mutations, p.G61E, p.D374N, and p.R368H,
      in seven of nine unrelated PCG index patients (78%). Six patients had homozygous
      mutations and one had a compound heterozygous mutation. Causative mutations were
      not identified in two families. In family 4, the index patient was found to be
      heterozygous for the p.E229K variant. In family 6, although affected individuals
      were found to be homozygous in the CYP1B1 region, no mutation could be
      identified. CONCLUSIONS: This study indicates that CYP1B1 could be the
      predominant cause of PCG in the Omani population (78%). Omani PCG patients show
      allelic heterogeneity. Further studies are needed to delineate the spectrum of
      CYP1B1mutations in Omani PCG families and to identify new or modifier genes
      contributing to the manifestations of PCG in this region.

PMID- 19597569
TI  - A novel mutation in CRYAB associated with autosomal dominant congenital nuclear
      cataract in a Chinese family.
AB  - PURPOSE: To identify the genetic defects associated with autosomal dominant
      congenital nuclear cataract in a Chinese family. METHODS: Clinical data were
      collected, and the phenotypes of the affected members in this family were
      recorded by slit-lamp photography. Genomic DNA was isolated from peripheral
      blood. Mutations were screened in cataract-associated candidate genes through
      polymerase chain reaction (PCR) analyses and sequencing. Structural models of the
      wild-type and mutant alphaB-crystallin were generated and analyzed by SWISS
      MODEL. RESULTS: Mutation screening identified only one heterozygous G-->A
      transition at nucleotide 32 in the first exon of alphaB-crystallin (CRYAB),
      resulting in an amino acid change from arginine to histidine at codon 11 (R11H).
      This mutation segregated in all available affected family members but was not
      observed in any of the unaffected persons of the family. The putative mutation
      disrupted a restriction site for the enzyme, Fnu4HI, in the affected family
      members. The disruption, however, was not found in any of the randomly selected
      ophthalmologically normal individuals or in 40 unrelated senile cataract
      patients. Computer-assisted prediction suggested that this mutation affected the
      biochemical properties as well as the structure of alphaB-crystallin.
      CONCLUSIONS: These results supported the idea that the novel R11H mutation was
      responsible for the autosomal dominant nuclear congenital cataract in this
      pedigree.

PMID- 19597568
TI  - Genome-wide transcription analysis of histidine-related cataract in Atlantic
      salmon (Salmo salar L).
AB  - PURPOSE: Elevated levels of dietary histidine have previously been shown to
      prevent or mitigate cataract formation in farmed Atlantic salmon (Salmo salar L).
      The aim of this study was to shed light on the mechanisms by which histidine
      acts. Applying microarray analysis to the lens transcriptome, we screened for
      differentially expressed genes in search for a model explaining cataract
      development in Atlantic salmon and possible markers for early cataract diagnosis.
      METHODS: Adult Atlantic salmon (1.7 kg) were fed three standard commercial salmon
      diets only differing in the histidine content (9, 13, and 17 g histidine/kg diet)
      for four months. Individual cataract scores for both eyes were assessed by slit
      lamp biomicroscopy. Lens N-acetyl histidine contents were measured by high
      performance liquid chromatography (HPLC). Total RNA extracted from whole lenses
      was analyzed using the GRASP 16K salmonid microarray. The microarray data were
      analyzed using J-Express Pro 2.7 and validated by quantitative real-time
      polymerase chain reaction (qRT-PCR). RESULTS: Fish developed cataracts with
      different severity in response to dietary histidine levels. Lens N-acetyl
      histidine contents reflected the dietary histidine levels and were negatively
      correlated to cataract scores. Significance analysis of microarrays (SAM)
      revealed 248 significantly up-regulated transcripts and 266 significantly down
      regulated transcripts in fish that were fed a low level of histidine compared to
      fish fed a higher histidine level. Among the differentially expressed transcripts
      were metallothionein A and B as well as transcripts involved in lipid metabolism,
      carbohydrate metabolism, regulation of ion homeostasis, and protein degradation.
      Hierarchical clustering and correspondence analysis plot confirmed differences in
      gene expression between the feeding groups. The differentially expressed genes
      could be categorized as "early" and "late" responsive according to their
      expression pattern relative to progression in cataract formation. CONCLUSIONS:
      Dietary histidine regimes affected cataract formation and lens gene expression in
      adult Atlantic salmon. Regulated transcripts selected from the results of this
      genome-wide transcription analysis might be used as possible biological markers
      for cataract development in Atlantic salmon.

PMID- 19597570
TI  - Investigation of parent-of-origin effect in comitant strabismus using MOD score
      analysis.
AB  - PURPOSE: Comitant strabismus is a common pediatric ophthalmic disorder with both
      genetic and non-genetic factors contributing to its etiology. The aim of the
      current study is to investigate the phenomenon of a parent-of-origin effect,
      genomic imprinting, as a possible mode of inheritance in comitant strabismus.
      METHODS: We performed parametric genome-wide MOD score (model-maximized LOD
      score) linkage analysis, incorporating imprinting effects, for 382 microsatellite
      markers in a sample of 258 individuals (117 males and 141 females) from 55
      Japanese families with comitant strabismus. We included individuals as affected
      patients if they presented with comitant esotropia or exotropia based on
      ophthalmic examination, history taking, or analysis of medical records. RESULTS:
      Significant or suggestive linkage to comitant strabismus with evidence of
      maternal or paternal imprinting was detected at D4S1575 (4q28.3), D7S486
      (7q31.2), D11S1320 (11q24.2), D12S324 (12q24.32), and D19S420 (19q13.11). Using
      the MOD score approach, we found new evidence of linkage to comitant strabismus
      at three loci on chromosomes 6q26 (MOD(imp)=MOD(reg)=3.75), 12q24.32
      (MOD(imp)=3.36), and 19q13.11 (MOD(imp)=3.79). CONCLUSIONS: The results suggest
      that the parent-of-origin effect may play a role in the etiology of comitant
      strabismus.

PMID- 19597571
TI  - Function of the tryptophan metabolite, L-kynurenine, in human corneal endothelial
      cells.
AB  - PURPOSE: Penetrating keratoplasty has been the mainstay for the treatment of
      blindness and is the most common form of tissue transplantation worldwide. Due to
      significant rates of rejection, treatment of immunological transplant reactions
      is of wide interest. Recently in a mouse model, the overexpression of
      indoeleamine 2,3 dioxigenase (IDO) was led to an extension in corneal allograft
      survival. L-kynurenine is a tryptophan metabolite, which may render activated T
      cells apoptotic and therefore might modulate an allogenous transplant reaction.
      The function of L-kynurenine in the human cornea remains unclear. We analyzed the
      expression levels of IDO in human corneal endothelial cells (HCECs) and
      downstream tryptophan/kynurenine mechanisms in cell culture. METHODS: An
      immunological activation profile was determined in proliferation assays of
      monocytes from healthy donors. Reversed-phase high pressure liquid chromatography
      (HPLC), western blot, real time polymerase chain reaction (PCR), and microarray
      analyses were used. The expression of IDO and immunological infiltration of
      rejected human corneal allografts (n=12) were analyzed by immunohistochemistry.
      RESULTS: We found IDO and an associated tryptophan/kynurenine transporter protein
      exchange mechanism upregulated by inflammatory cytokines in HCECs. The inhibition
      of T-cell proliferation might depend on rapid delivery of the tryptophan
      metabolite, L-kynurenine, to the local corneal environment. Microarray analysis
      gives evidence that the large amino acid transporter 1 (LAT1) transporter protein
      is responsible for this mechanism. CONCLUSIONS: Our data support that adequate
      levels of functional L-kynurenine might contribute to the maintenance of a
      relative immune privilege in the ocular anterior chamber, thereby contributing to
      the preservation of corneal allogeneic cells.

PMID- 19597572
TI  - Matrix metalloproteinase inhibitors (MMPIs) from marine natural products: the
      current situation and future prospects.
AB  - Matrix metalloproteinases (MMPs) are a family of more than twenty five secreted
      and membrane-bound zinc-endopeptidases which can degrade extracellular matrix
      (ECM) components. They also play important roles in a variety of biological and
      pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been
      identified as potential therapeutic candidates for metastasis, arthritis, chronic
      inflammation and wrinkle formation. Up to present, more than 20,000 new compounds
      have been isolated from marine organisms, where considerable numbers of these
      naturally occurring derivatives are developed as potential candidates for
      pharmaceutical application. Eventhough the quantity of marine derived MMPIs is
      less when compare with the MMPIs derived from terrestrial materials, huge
      potential for bioactivity of these marine derived MMPIs has lead to large number
      of researches. Saccharoids, flavonoids and polyphones, fatty acids are the most
      important groups of MMPIs derived from marine natural products. In this review we
      focus on the progress of MMPIs from marine natural products.

PMID- 19597573
TI  - Fibrinolytic compounds isolated from a brown alga, Sargassum fulvellum.
AB  - Two of bioactive natural products were founded in a brown alga, Sargassum
      fulvellum. After isolation and purification, the molecular structures of these
      two products were investigated by NMR spectroscopy and GC-mass spectroscopy. The
      two compounds were identified to be 1-O-palmitoyl-2-O-oleoyl-3-O-(alpha-D
      glucopyranosyl)-glycerol (POGG) and 1-O-myristoyl-2-O-oleoyl-3-O-(alpha-D
      glucopyranosyl)-glycerol (MOGG) which were obtained from Sargassum fulvellum for
      the first time. POGG and MOGG showed fibrinolytic activity in the reaction system
      of pro-u-PA and plasminogen.

PMID- 19597575
TI  - Broad-spectrum antimicrobial epiphytic and endophytic fungi from marine
      organisms: isolation, bioassay and taxonomy.
AB  - In the search for new marine derived antibiotics, 43 epi- and endophytic fungal
      strains were isolated from the surface or the inner tissue of different marine
      plants and invertebrates. Through preliminary and secondary screening, 10 of them
      were found to be able to produce broad-spectrum antimicrobial metabolites. By
      morphological and molecular biological methods, three active strains were
      characterized to be Penicillium glabrum, Fusarium oxysporum, and Alternaria
      alternata.

PMID- 19597576
TI  - Advances in marine microbial symbionts in the china sea and related
      pharmaceutical metabolites.
AB  - Marine animals and plants such as sponges, sea squirts, corals, worms and algae
      host diverse and abundant symbiotic microorganisms. Marine microbial symbionts
      are possible the true producers or take part in the biosynthesis of some
      bioactive marine natural products isolated from the marine organism hosts.
      Investigation of the pharmaceutical metabolites may reveal the biosynthesis
      mechanisms of related natural products and solve the current problem of supply
      limitation in marine drug development. This paper reviews the advances in
      diversity revelation, biological activity and related pharmaceutical metabolites,
      and functional genes of marine microbial symbionts from the China Sea.

PMID- 19597577
TI  - Marine antimalarials.
AB  - Malaria is an infectious disease causing at least 1 million deaths per year, and,
      unfortunately, the chemical entities available to treat malaria are still too
      limited. In this review we highlight the contribution of marine chemistry in the
      field of antimalarial research by reporting the most important results obtained
      until the beginning of 2009, with particular emphasis on recent discoveries.
      About 60 secondary metabolites produced by marine organisms have been grouped
      into three structural types and discussed in terms of their reported antimalarial
      activities. The major groups of metabolites include isonitrile derivatives,
      alkaloids and endoperoxide derivatives. The following discussion evidences that
      antimalarial marine molecules can efficiently integrate the panel of lead
      compounds isolated from terrestrial sources with new chemical backbones and,
      sometimes, with unique functional groups.

PMID- 19597578
TI  - Chemopreventive effects of sarcophine-diol on ultraviolet B-induced skin tumor
      development in SKH-1 hairless mice.
AB  - Sarcophine-diol (SD), one of the structural modifications of sarcophine, has
      shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O
      tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1
      mice. The objective of this study was to determine the chemopreventive effects of
      SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more
      relevant to human skin cancer, and to determine the possible mechanisms of
      action. Carcinogenesis was initiated and promoted by UVB radiation. Female
      hairless SKH-1 mice were divided into two groups having 27 mice in each group:
      control and SD treatment. The control group was topically treated with 100 microL
      acetone and SD treatment group was topically treated with SD (30 microg/100
      microL in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts
      were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of
      caspases were investigated to elucidate the possible mechanism of action. The
      proteins from epidermal homogenates of experimental mice were used for SDS-PAGE
      and Western blotting using specific antibodies against caspase-3, caspase-8 and
      caspase-9 respectively. TUNEL assay was used for determining DNA fragmented
      apoptotic cells in situ. Results showed that at the end of experiment, tumor
      multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per
      mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented
      apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8.
      This study clearly suggested that SD could be an effective chemopreventive agent
      for UVB-induced skin cancer by inducing caspase dependent apoptosis.

PMID- 19597579
TI  - Aplysinopsins--marine indole alkaloids: chemistry, bioactivity and ecological
      significance.
AB  - Aplysinopsins are tryptophan-derived marine natural products isolated from
      numerous genera of sponges and scleractinian corals, as well as from one sea
      anemone and one nudibranch. Aplysinopsins are widely distributed in the Pacific,
      Indonesia, Caribbean, and Mediterranean regions. Up to date, around 30 analogues
      occurring in Nature have been reported. Natural aplysinopsins differ in the
      bromination pattern of the indole ring, variation in the structure of the C ring,
      including the number and position of N-methylation, the presence and
      configuration of the C-8-C-1' double bond, and the oxidation state of the 2
      aminoimidazoline fragment. Aplysinopsins can also occur in the form of dimers.
      This review summarizes 30 years' research on aplysinopsins. The origin, isolation
      sources, chemistry, bioactivity, and ecological functions of aplysinopsins are
      comprehensively reviewed.

PMID- 19597580
TI  - Sphaeroane and neodolabellane diterpenes from the red alga Sphaerococcus
      coronopifolius.
AB  - Investigation of minor metabolites in the extracts of the red alga Sphaerococcus
      coronopifolius collected from the rocky coasts of Corfu Island in the Ionian Sea
      yielded two new diterpene alcohols, sphaerollanes I, and II (1, 2) featuring
      neodolabellane skeletons, and the new sphaeroane diterpene alcohol 16-hydroxy-9S*
      acetoxy-8-epi-isosphaerodiene-2 (3), along with two previously reported
      metabolites 4, 5. The structures of the new natural products, as well as their
      relative stereochemistry, were elucidated on the basis of extensive spectral
      analysis, including 2D-NMR experiments.

PMID- 19597581
TI  - Deoxyamphimedine, a pyridoacridine alkaloid, damages DNA via the production of
      reactive oxygen species.
AB  - Marine pyridoacridines are a class of aromatic chemicals that share an 11H
      pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse
      biological activities including cytotoxicity, fungicidal and bactericidal
      properties, production of reactive oxygen species (ROS) and topoisomerase
      inhibition. These activities are often dependent on slight modifications to the
      pyridoacridine skeleton. Here we demonstrate that while structurally similar to
      neoamphimedine and amphimedine, the biological activity of deoxyamphimedine
      differs greatly. Deoxyamphimedine damages DNA in vitro independent of
      topoisomerase enzymes through the generation of reactive oxygen species. Its
      activity was decreased in low oxygen, with the removal of a reducing agent and in
      the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in
      cells sensitive to single or double strand DNA breaks, consistent with the in
      vitro activity.

PMID- 19597584
TI  - Expression, purification and bioactivities analysis of recombinant active peptide
      from shark liver.
AB  - The Active Peptide from Shark Liver (APSL) was expressed in E. coli BL21 cells.
      The cDNA encoding APSL protein was obtained from shark regenerated hepatic tissue
      by RT-PCR, then it was cloned in the pET-28a expression vector. The expressed
      fusion protein was purified by Ni-IDA affinity chromatography. SDS-PAGE and HPLC
      analysis showed the purity of the purified fusion protein was more than 98%. The
      recombinant APSL (rAPSL) was tested for its biological activity both in vitro, by
      its ability to improve the proliferation of SMMC7721 cells, and in vivo, by its
      significant protective effects against acute hepatic injury induced by CCl(4) and
      AAP (acetaminophen) in mice. In addition, the rAPSL could decrease the blood
      glucose concentration of mice with diabetes mellitus induced by alloxan. Paraffin
      sections of mouse pancreas tissues showed that rAPSL (3 mg/kg) could effectively
      protect mouse islets from lesions induced by alloxan, which indicated its
      potential application in theoretical research and industry.

PMID- 19597583
TI  - New azaphilones, seco-chaetomugilins A and D, produced by a marine-fish-derived
      Chaetomium globosum.
AB  - Seco-chaetomugilins A and D were isolated from a strain of Chaetomium globosum
      that was originally isolated from the marine fish Mugil cephalus, and their
      absolute stereostructures were elucidated on the basis of spectroscopic analyses,
      including 1D and 2D NMR techniques, along with the chemical transformation from
      known chaetomugilins A and D. Seco-chaetomugilin D exhibited growth inhibitory
      activity against cultured P388, HL-60, L1210, and KB cells.

PMID- 19597588
TI  - New generation of metal string complexes: strengthening metal-metal interaction
      via naphthyridyl group modulated oligo-alpha-pyridylamido ligands.
AB  - To design new metal string complexes, several naphthyridyl group modulated oligo
      alpha-pyridylamido ligands have been synthesized in the past five years. Because
      these ligands are less anionic than pyridylamido ligands, the resulting metal
      string complexes tend to form reduced mixed-valence [Ni(2)(napy)(4)](3+)
      dinuclear units which contain a delocalized unpaired electron and thus
      significantly enhance the conductance of metal string complexes. Furthermore, the
      asymmetric naphthyridyl group modulated oligo-alpha-pyridylamido ligands can
      stabilize the central heteronuclear or charge disproportionational metal
      frameworks, providing a plausible strategy to build inorganic molecular
      rectifiers.

PMID- 19597589
TI  - Aggregation-induced emission: phenomenon, mechanism and applications.
AB  - It is textbook knowledge that chromophore aggregation generally quenches light
      emission. In this feature article, we give an account on how we observed an
      opposite phenomenon termed aggregation-induced emission (AIE) and identified the
      restriction of intramolecular rotation as a main cause for the AIE effect. Based
      on the mechanistic understanding, we developed a series of new fluorescent and
      phosphorescent AIE systems with emission colours covering the entire visible
      spectral region and luminescence quantum yields up to unity. We explored high
      tech applications of the AIE luminogens as, for example, fluorescence sensors
      (for explosive, ion, pH, temperature, viscosity, pressure, etc.), biological
      probes (for protein, DNA, RNA, sugar, phospholipid, etc.), immunoassay markers,
      PAGE visualization agents, polarized light emitters, monitors for layer-by-layer
      assembly, reporters for micelle formation, multistimuli-responsive nanomaterials,
      and active layers in the fabrication of organic light-emitting diodes.

PMID- 19597590
TI  - A four-shell, 136-metal 3d-4f heterometallic cluster approximating a rectangular
      parallelepiped.
AB  - A nanosized heterometallic cluster containing 60 La(III) and 76 Ni(II) ions,
      which are arranged into a four-shell, nest-like framework structure, was obtained
      by the hydrolytic reaction of the mixed La(NO(3))(3)-Ni(NO(3))(2) system using
      iminodiacetate as an ancillary ligand to control the hydrolysis.

PMID- 19597591
TI  - Remarkable regioselectivity in the preparation of the first heterotrimetallic
      Mo[quadruple bond]W...Cr chain.
AB  - Addition of CrCl(2) to the dinuclear synthon MoW(dpa)(4) yields a
      regioselectively formed heterotrimetallic Mo[quadruple bond]W...Cr chain;
      computational studies suggest that the polarization of the Mo[quadruple bond]W
      quadruple bond partially accounts for this unexpected selectivity.

PMID- 19597582
TI  - Antitumor compounds from marine actinomycetes.
AB  - Chemotherapy is one of the main treatments used to combat cancer. A great number
      of antitumor compounds are natural products or their derivatives, mainly produced
      by microorganisms. In particular, actinomycetes are the producers of a large
      number of natural products with different biological activities, including
      antitumor properties. These antitumor compounds belong to several structural
      classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides,
      macrolides, non-ribosomal peptides and others, and they exert antitumor activity
      by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II
      inhibition, mitochondria permeabilization, inhibition of key enzymes involved in
      signal transduction like proteases, or cellular metabolism and in some cases by
      inhibiting tumor-induced angiogenesis. Marine organisms have attracted special
      attention in the last years for their ability to produce interesting
      pharmacological lead compounds.

PMID- 19597592
TI  - Organic conducting wire formation on a TiO2 nanocrystalline structure: towards
      long-lived charge separated systems.
AB  - Conjugated polymer monolayers have successfully been fabricated on a TiO(2)
      nanocrystalline electrode by a lateral intermonomer charge transfer process,
      extending the photo-induced charge separated state lifetime by a factor of 50-70.

PMID- 19597593
TI  - Single-molecule magnet Fe9 supramolecular dimers: a theoretical approach to
      intramolecular and intermolecular exchange interactions.
AB  - A theoretical study using methods based on density functional theory makes it
      possible to study the intramolecular and intermolecular exchange interactions in
      Fe(9) supramolecular dimers.

PMID- 19597594
TI  - A facile approach to hexanary chalcogenoborate featuring a 3-D chiral honeycomb
      like open-framework constructed from rare-earth consolidating thiogallate-closo
      dodecaborate.
AB  - A novel chiral open-framework structural hexanary chalcogenoborate,
      (K(3)I)[SmB(12)(GaS(4))(3)] (1), was obtained by a facile approach using boron as
      the reducing reagent; it shows weak SHG-activity and is transparent in the mid-IR
      region.

PMID- 19597595
TI  - A tailored spirooxazine dimer as a photoswitchable binding tool.
AB  - A uniquely angled spirooxazine dimer was synthesized as a smart photoswitch for
      sensing and delivery applications; the dimer showed reversible binding and
      release ability towards a palladium catalyst.

PMID- 19597596
TI  - Stable diarylnitroxide diradical with triplet ground state.
AB  - Nitroxide diradical , the first isolated diarylnitroxide diradical, is stable in
      the solid state at room temperature and it possesses triplet ground state with
      strong ferromagnetic coupling.

PMID- 19597597
TI  - Formation of linear main-chain polypseudorotaxanes with supramolecular polymer
      backbones via two self-sorting host-guest recognition motifs.
AB  - Based on two self-sorting host-guest recognition motifs, novel linear main-chain
      polypseudorotaxanes with supramolecular polymer backbones have been constructed
      from three components in solution at high concentrations.

PMID- 19597598
TI  - Octahedral Fe3O4 nanoparticles and their assembled structures.
AB  - Octahedral Fe(3)O(4) nanoparticles, showing ferrimagnetic behavior, were
      synthesised by a facile route and due to their monodispersity and anisotropic
      shape the nanoparticles self-assemble to superlattices with well-defined
      orientation.

PMID- 19597599
TI  - A micrometer-size TiO2 single-crystal photocatalyst with remarkable 80% level of
      reactive facets.
AB  - A micro-sheet anatase TiO(2) single crystal photocatalyst with a remarkable 80%
      level of reactive {001} facets was synthesized via a microwave-assisted
      hydrothermal route involving titanium tetrafluoride and a tetrafluoroborate-based
      ionic liquid.

PMID- 19597600
TI  - Monolithic aerogels of silver modified cadmium sulfide colloids.
AB  - Monolithic mesoporous aerogels comprising cadmium sulfide nanoparticles partially
      coated with metallic silver (CdS-Ag) are synthesized, and it is determined that
      the concentration of silver has a significant impact on the resultant CdS-Ag
      aerogel morphology and porosity.

PMID- 19597601
TI  - First structurally characterized mono- and dinuclear ruthenium complexes derived
      from zwitterionic quinonoid ligands.
AB  - Electron transfer and delocalization of the pi systems were investigated in mono-
      and dinuclear Ru complexes with the zwitterionic ligand L = N,N'-diisopropyl-2
      amino-5-alcoholate-1,4-benzoquinonemonoiminium.

PMID- 19597602
TI  - Optical detection of glucose by CdS quantum dots immobilized in smart microgels.
AB  - Reversible fluorescence quenching and anti-quenching of CdS quantum dots
      immobilized in boronic acid-based microgels can be used for the optical detection
      of glucose.

PMID- 19597603
TI  - Ag nanowires enhanced upconversion emission of NaYF4:Yb,Er nanocrystals via a
      direct assembly method.
AB  - Enhanced upconversion emission of NaYF(4):Yb,Er nanocrystals with Ag nanowires
      was observed; the enhancement factor of red emission is larger than that of green
      emission, and it can be further increased with Ag islands composed of larger Ag
      particles.

PMID- 19597605
TI  - Two-directional ring-opening cross-metathesis.
AB  - Two-directional ring-opening cross-metathesis of a range of cyclic alkenes with a
      variety of electron deficient alkenes has been accomplished; it was found that
      the process is quite general and gives complete selectivity for the E,E-dienes,
      making this a very useful and high-yielding protocol for two-directional chain
      synthesis.

PMID- 19597604
TI  - Asymmetric autocatalysis induced by meteoritic amino acids with hydrogen isotope
      chirality.
AB  - Achiral meteoritic amino acids, glycine and alpha-methylalanine, with hydrogen
      isotope (D/H) chirality, acted as the source of chirality in asymmetric
      autocatalysis with amplification of ee to afford highly enantioenriched 5
      pyrimidyl alkanols.

PMID- 19597606
TI  - Direct synthesis of large-pore ethane-bridged mesoporous organosilica
      functionalized with carboxylic groups.
AB  - Carboxylic groups have been incorporated in ethane-bridged PMO by one-pot
      synthesis using a triblock copolymer as template; their pK(a) measured by
      titration is higher than that of same groups incorporated in SBA-15.

PMID- 19597607
TI  - Amino-functionalized carbon nanotubes as solid basic catalysts for the
      transesterification of triglycerides.
AB  - Multiwalled carbon nanotubes grafted with various amino groups show high activity
      and stability when used as basic catalysts for the transesterification of
      triglycerides.

PMID- 19597608
TI  - Use of 4-piperidones in one-pot syntheses of novel, high-molecular-weight linear
      and virtually 100%-hyperbranched polymers.
AB  - 4-Piperidone and 4-alkyl piperidones react selectively with aromatic hydrocarbons
      in a mixture of trifluoromethanesulfonic acid (TFSA) and CH(2)Cl(2) to give
      linear polymers, while N-(2-phenethyl)piperidone undergoes self-polymerization to
      yield virtually 100%-hyperbranched polymer.

PMID- 19597609
TI  - A novel biodegradable and thermosensitive polymer with PEG-analogue
      macromolecular structure.
AB  - A non-toxic PEG-analogue designed with polyester backbone and oligo(ethylene
      glycol) pendant chains combines well-defined reversible thermosensitivity with
      controlled bio-degradation and anti-immunogeneity properties.

PMID- 19597610
TI  - Zirconocene-mediated ligand-switched selective cleavage of active and inert
      carbon-carbon bonds in allylcyclopropanes.
AB  - Selective cleavage of both active and inert C-C bonds in substituted
      allylcyclopropanes was realized via a novel ligand-controlled approach using
      zirconocene(II)-1-butene or zirconocene(II)-benzyne complexes.

PMID- 19597611
TI  - A cryptand based chemodosimetric probe for naked-eye detection of mercury(II) ion
      in aqueous medium and its application in live cell imaging.
AB  - A cryptand-rhodamine conjugated chemodosimeter can detect Hg(II) ion in aqueous
      medium selectively at ppb level in the presence of other biologically relevant
      metal ions and also shows a good viability to the HEK 293 cell line.

PMID- 19597612
TI  - Photoisomerization of an azobenzene gel by pulsed laser irradiation.
AB  - A decalin gel consisting of a 3,3'-bis[{(octylamino)carbonyl}propoxy]azobenzene
      derivative with H-aggregation showed a photon-density dependent E-Z
      isomerization, indicating the cooperating isomerization of each module.

PMID- 19597613
TI  - Solubility adjustable nanoparticles stabilized by a novel PVP based family:
      synthesis, characterization and catalytic properties.
AB  - Systematic fabrication of nanoparticle stabilizers can substantially modify the
      properties of prepared nanoparticles; here the synthesis of solubility adjustable
      nanoparticles is achieved by employing a family of polarity modulated
      stabilizers.

PMID- 19597614
TI  - Blue to green shifted fluorescence in inter- and intramolecular hydrogen bonded
      di(benzimidazol-2-yl)benzene.
AB  - Interconversion of intermolecular H-bonded di(benzimidazol-2-yl)benzene to an
      intramolecular H-bonded isomer shows a strong blue to green shifted fluorescence.

PMID- 19597615
TI  - Remarkable effect of 2,2'-bipyridyl: mild and highly chemoselective deprotection
      of methoxymethyl (MOM) ethers in combination with TMSOTf (TESOTf)-2,2'-bipyridyl.
AB  - The remarkable effect of 2,2'-bipyridyl led to the successful development of the
      mild and highly chemoselective deprotection method of methoxymethyl (MOM) ethers
      using the combination of TMSOTf (or TESOTf) and 2,2'-bipyridyl; this method can
      be applied to the direct conversion of the MOM group to other ethereal protective
      groups (e.g. benzyloxymethyl) with the corresponding alcohols.

PMID- 19597616
TI  - Bonding mode of a new bis-phosphine-borane alkyl ligand to a Rh(I) species.
AB  - The stoichiometric reaction of [Rh(COD)Cl](2) with the anion resulting from the
      deprotonation of dppm(BH(3))(2) yielded a new alkyl Rh(I) complex; the
      coordination modes of the BH(3) groups are discussed on the basis of X-ray data,
      variable temperature multinuclear NMR experiments and DFT studies.

PMID- 19597617
TI  - The organocatalytic addition of bis(arylsulfonyl)methane to alpha,beta
      unsaturated aldehydes and the synthesis of optically-enriched 3-methyl-alkanols.
AB  - An indirect organocatalytic method for the beta-methylation of alpha,beta
      unsaturated aldehydes that involves the addition of bis(arylsulfonyl)methane
      catalyzed by prolinol derivatives and further elimination of the chameleonic
      sulfonyl groups is presented.

PMID- 19597618
TI  - Hydrodechlorination of chlorophenols at low temperature on a novel Pd catalyst.
AB  - Pd/mesoporous silica-carbon nanocomposites with 3.2 nm Pd particles, prepared by
      a simple wetness impregnation method, have demonstrated high activity at 258 K
      for the hydrodechlorination of chlorophenols with a high selectivity.

PMID- 19597619
TI  - Structure-energy relations in hen egg white lysozyme observed during refolding
      from a quenched unfolded state.
AB  - We use infrared spectroscopy to study the evolution of protein folding
      intermediate structures on arbitrarily slow time scales by rapidly quenching
      thermally unfolded hen egg white lysozyme in a glassy matrix, followed by
      reheating of the protein to refold; upon comparison with differential scanning
      calorimetric experiments, low-temperature structural changes that precede the
      formation of energetic native contacts are revealed.

PMID- 19597620
TI  - A DNA-binding Gd chelate for the detection of cell death by MRI.
AB  - GadoTO, a MR contrast agent for the detection of cell death, consists of a
      nucleic acid-binding fluorophore attached to a gadolinium chelate.

PMID- 19597621
TI  - Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles
      as lymphatic targeted drug delivery vehicles.
AB  - Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles
      were readily taken up into lymph vessels and delivered gemcitabine to lymph nodes
      with high efficiency under the guidance of a magnetic field.

PMID- 19597622
TI  - Iron-catalyzed thioetherification of thiols with aryl iodides.
AB  - FeCl(3) in combination with bisphosphine ligands represents an efficient catalyst
      system for the cross-coupling of aryl- and alkyl thiols with aryl iodides, a
      broad spectrum of functional groups can be tolerated during the catalysis.

PMID- 19597623
TI  - An easily prepared hypersensitive water-soluble fluorescent probe for mercury(II)
      ions.
AB  - A hypersensitive water-soluble fluorescent probe, dansyl-L-tryptophan methyl
      ester (1), was easily prepared for the detection of Hg(2+) with a significantly
      improved detection limit (5 nM vs. 500 nM) in buffered aqueous solution.

PMID- 19597624
TI  - Surface mediated synthesis of 2D covalent organic frameworks: 1,3,5-tris(4
      bromophenyl)benzene on graphite(001), Cu(111), and Ag(110).
AB  - The on surface synthesis of a two-dimensional (2D) covalent organic framework
      from a halogenated aromatic monomer under ultra-high vacuum conditions is shown
      to be dependent on the choice of substrate.

PMID- 19597626
TI  - A limited surgical approach for pastern arthrodesis in horses with severe
      osteoarthritis.
AB  - Osteoarthritis of the proximal interphalangeal joint (PIPJ) is a common cause of
      chronic lameness in the horse that requires surgical arthrodesis when medical
      management is no longer able to alleviate pain. Surgical principles for
      successful PIPJ arthrodesis include articular cartilage debridement and rigid
      fixation. To completely debride articular cartilage, the collateral ligaments and
      extensor tendon are transected, disarticulating the joint. The purpose of this
      study was to demonstrate that in chronically lame horses with periarticular new
      bone formation and osteoarthritis, successful arthrodesis occurs without joint
      disarticulation and complete articular cartilage debridement. We hypothesised
      that complete articular debridement is not necessary, thus allowing for a less
      invasive surgical approach that decreases surgical time and hospitalisation with
      comparable success rates to previous reports. Medical records from 2000-2007 were
      reviewed for PIPJ disease. Information regarding lameness, surgical time and
      hospitalisation were retrieved from 11 horses (12 limbs). Follow-up information
      was obtained via a telephone interview and a re-evaluation. Average hospital and
      surgery times were shorter than previous reports at 19 days and 111 minutes
      respectively. Lameness decreased at least one grade in 92% of limbs. 73% of
      owners would elect to operate again. The data suggests that successful
      arthrodesis occurs without joint disarticulation and complete articular cartilage
      debridement.

PMID- 19597627
TI  - Does a fabella-tibial suture alter the outcome for dogs with cranial cruciate
      ligament insufficiency undergoing arthrotomy and caudal pole medial meniscectomy?
AB  - OBJECTIVES: The objective of this study was to evaluate the effects of fabella
      tibial suture (FTS) on long-term outcome in dogs with cranial cruciate ligament
      (CCL) insufficiency and concurrent medial meniscal tear (MMT) that were managed
      by an open, caudal pole medial meniscectomy (CPMM). METHODS: A retrospective
      review was performed of the clinical records of dogs treated for CCL
      insufficiency with concurrent MMT by open CPMM, with or without the non-random
      addition of a nylon FTS according to surgeon preference, during the period of
      2001 to 2004. The Bristol Osteoarthritis in Dogs questionnaire was modified for
      owner assessment of outcome using a visual analogue scale based on several
      criteria: level of activity, disability, severity of lameness and frequency of
      lameness before and after surgery. RESULTS: Completed questionnaires from 31 dog
      owners were received. A FTS was used after CPMM in 22 dogs (FTS group), but in
      nine dogs (control group) only a CPMM was performed. The median time to follow up
      was longer in the FTS group (25 months) than the control group (16 months)
      (P=0.03). There were not any significant differences between the two groups
      before and after surgery for the following: disability, activity, frequency of
      lameness, severity of lameness, ability to climb stairs and ability to sit down.
      CLINICAL SIGNIFICANCE: The placement of a FTS following stifle joint arthrotomy
      and CPMM in dogs with CCL deficiency and concurrent MMT may not be a significant
      factor affecting the ultimate surgical outcome, although our study is limited by
      the non-randomised study design.

PMID- 19597628
TI  - The cranial instrument port in arthroscopy of the canine shoulder joint.
AB  - We describe the creation of a cranial instrument portal for shoulder joint
      arthroscopy in the dog using a target device that has been successfully employed
      for the caudal access. We compared the method with a conventional triangulation
      technique. The shoulder joints of 60 dog cadavers were investigated by
      arthroscopy and the two methods were compared on the basis of pre-defined
      parameters of outcome. Time, the number of trials, success, damage to cartilage
      and the accessibility of intra-articular structures were assessed. The anatomical
      localisation of the working cannula in muscles was also documented. In general,
      the new method permitted more successful insertion of the working cannula. This
      was achieved in a shorter period of time and was associated with fewer insertion
      attempts as well as less damage to joint cartilage. Intra-articular structures
      could be readily approached through the working cannula with both methods.
      Predetermined, clinically relevant points were comparatively more accessible with
      the new technique. Independent of the method, in only a few cases, the working
      cannula perforated neither muscles nor tendons when accessing the joint. It may
      be concluded that the new method using a target device is simpler and safer and
      offers a standardised technique to establish a cranial instrument port.

PMID- 19597629
TI  - A biomechanical comparison of 3.5 locking compression plate fixation to 3.5
      limited contact dynamic compression plate fixation in a canine cadaveric distal
      humeral metaphyseal gap model.
AB  - 3.5 locking compression plate (LCP) fixation was compared to 3.5 limited contact
      dynamic compression plate (LC-DCP) fixation in a canine cadaveric, distal humeral
      metaphyseal gap model. Thirty paired humeri from adult, large breed dogs were
      separated into equal groups based on testing: static compression, cyclic
      compression, and cyclic torsion. Humeral constructs stabilised with LCP were
      significantly stiffer than those plated with LC-DCP when loaded in static axial
      compression (P = 0.0004). When cyclically loaded in axial compression, the LCP
      constructs were significantly less stiff than the LC-DCP constructs (P = 0.0029).
      Constructs plated with LCP were significantly less resistant to torsion over 500
      cycles than those plated with LC-DCP (P<0.0001). The increased stiffness of LCP
      constructs in monotonic loading compared to constructs stabilised with non
      locking plates may be attributed to the stability afforded by the plate-screw
      interface of locking plates. The LCP constructs demonstrated less stiffness in
      dynamic testing in this model, likely due to plate-bone offset secondary to non
      anatomic contouring and occasional incomplete seating of the locking screws when
      using the torque-limiting screw driver. Resolution of these aspects of LCP
      application may help improve the stiffness of fixation in fractures modeled by
      the experimental set-up of this investigation.

PMID- 19597630
TI  - Pressure distribution between the deep digital flexor tendon and the navicular
      bone, and the effect of raising the heels in vitro.
AB  - The objectives of this study were to topographically map pressure distribution
      across the palmar surface of the navicular bone in response to forces applied by
      the deep digital flexor tendon (DDFT), and evaluate the effect of raising the
      heels in vitro . A rig was constructed to hold an equine cadaver limb and apply
      controlled pressure to the navicular bone from the DDFT. Pressure-sensitive paper
      was used to quantify and map the resultant pressure. Changes in response to heel
      wedges (5 degrees and 10 degrees ) were recorded. The areas subject to maximum
      pressure from the DDFT were: the central ridge, the paired symmetrical areas
      adjacent to the ridge and the distal edge of the palmar bone surface. These
      regions correspond to the known sites of navicular pathology. Heel wedges
      redistributed the pressure exerted on the palmar surface of the navicular bone,
      with measurements varying depending on fetlock angle and wedge angle. These in
      vitro results support the hypothesis that inappropriate forces exerted via the
      DDFT on the bone cause navicular disease. However, they throw doubt on the
      practice of shoeing such horses with heel wedges as the redistribution of
      pressure may increase the force exerted on regions predisposed to disease.

PMID- 19597631
TI  - Appendicular fracture repair in dogs using the locking compression plate system:
      47 cases.
AB  - The locking compression plate (LCP) has combination screw holes, making it
      possible to use the implant in three different ways; as a pure internal fixator
      using locking head screws, as a conventional compression plate using compression
      screws, or as a hybrid of the two. The experience with the LCP system in
      veterinary fracture repair is limited. The objective of this study was to
      evaluate the outcome of appendicular fractures in dogs, which were repaired with
      the LCP system combined with less invasive surgical techniques. Medical records
      and radiographs from 47 dogs were studied retrospectively. Thirty-four percent of
      the fractures were simple, six percent wedge and 60% comminuted fractures of the
      humerus (11 %), radius and ulna (30 %), femur (34 %) and of the tibia and fibula
      (25 %). The fractures were treated using the LCP as an internal fixator; in some
      cases as a plate and rod construct. Forty-six of 47 fractures reached
      radiographic union. Mean healing time of the fractures was seven weeks (95%
      confidence interval from 5.8 to 8.3 weeks). There were statistically significant
      differences in healing time between juvenile (age under one year) and adults.
      Complications in the form of implant failures and infections were encountered in
      approximately 11% of the cases. All implant failures were due to surgical errors.
      The LCP system in combination with a less invasive surgical approach was found
      advantageous in comminuted fractures where the LCP was used as a bridging plate,
      in situations when exact plate contouring was difficult, and when other implants
      prevented the use of bi-cortical screws.

PMID- 19597632
TI  - Effect of bending direction on the mechanical behaviour of interlocking nail
      systems.
AB  - OBJECTIVES: To compare the mechanical properties of various interlocking nail
      constructs in medio-lateral (ML) and cranio-caudal (CC) bending. METHODS:
      Synthetic bone models simulating a severely comminuted tibial fracture were
      treated with either screwed or bolted, 6 or 8 mm standard interlocking nails
      (ILN), or an angle-stable ILN (AS-ILN), after which they were then sequentially
      tested in ML and CC bending. Construct compliance, maximum angular deformation
      (MaxDef) and slack were statistically compared (p<0.05). RESULTS: The compliance
      of all constructs was significantly greater in CC than in ML bending. However,
      due to the presence of a greater slack in the ML plane, standard ILN constructs
      sustained significantly more deformation in that plane. Maximum deformation of
      the novel AS-ILN constructs was the smallest of all constructs and consistently
      occurred without slack regardless of bending direction. CLINICAL SIGNIFICANCE:
      This study suggested that standard ILN construct overall deformation and acute
      instability (slack) may be more critical in ML than in CC bending. Conversely,
      the small MaxDef and the absence of slack in both bending planes seen in novel
      angle-stable AS-ILN may provide optimal construct stability and in turn may be
      more conducive to bone healing.

PMID- 19597633
TI  - A preliminary retrospective survey of injuries occurring in dogs participating in
      canine agility.
AB  - OBJECTIVES: Little is known about the risks of injury to dogs participating in
      the relatively new sport of canine agility. The purpose of this study was to
      identify the factors that put the participating dog at risk as well as determine
      the anatomical sites that were most commonly injured. METHODS: A retrospective
      survey using a paper and web-based data collection instrument was used to
      evaluate dogs participating in the sport of canine agility. RESULTS: Of the 1627
      dogs included in the study, 33% were injured, and of those 58% were injured in
      competition. Most injuries occurred on dry outdoor surfaces. Border Collies were
      the most commonly injured, and injuries were in excess of what would be expected
      from their exposure. For all dogs, soft tissue injuries were most common. The
      shoulders and backs of dogs were most commonly injured. Dogs were most commonly
      injured by contact with an obstacle. The A-frame, dogwalk and bar jump obstacles
      were responsible for nearly two-thirds of injuries that resulted from contact
      with the obstacle. CONCLUSIONS: Border Collies are at higher risk for injury than
      would be expected from their exposure. The A-frame, dogwalk and bar jump
      obstacles put the shoulders and backs of dogs at risk. CLINICAL RELEVANCE: For
      the first time, this study gives us insight into injuries occurring in dogs
      participating in canine agility. This will help direct prospective studies that
      evaluate the safety of individual obstacles, direct rule changes and enable
      practitioners to understand the risks of the sport.

PMID- 19597634
TI  - Does Osgood-Schlatter disease exist in the dog?
AB  - Osgood-Schlatter disease (OSD) is a condition affecting human adolescents in
      which there is partial separation of bone fragments from the tibial tuberosity at
      the site of insertion of the patellar ligament to the tibial tuberosity. Tensile
      trauma seems to be the most likely aetiology. Clinical signs in people consist of
      swelling and pain at the proximal part of the tibial tuberosity and around the
      distal end of patellar ligament. Radiographs frequently show small ossicles at
      the patellar ligament insertion. Conservative treatment is usually curative. The
      term OSD has also been used for the canine patient. However, radiographs of these
      patients typically show an enlarged radiolucent line at the apophyseal plate of
      the tibial tuberosity. This finding is consistent with a mild avulsion fracture
      of the canine tibial tuberosity. Based on the radiographic differences between
      the two species, it seems more appropriate to use the term OSD only for people.
      The purpose of this paper is to review the literature on OSD in people and the
      reports of injuries to the proximal tibial tuberosity in dogs. In addition, a new
      classification system for tibial tuberosity avulsion injuries in the immature dog
      is proposed, with an algorithm for management of this injury.

PMID- 19597635
TI  - Surgical approaches for minimally invasive plate osteosynthesis in dogs.
AB  - Fracture stabilisation techniques continue to evolve and to provide approaches
      which minimise the iatrogenic trauma associated with surgery. Minimally invasive
      plate osteosynthesis (MIPO) is a recently described method of biological internal
      fixation performed by introducing a bone plate via small insertional incisions
      that are made remote to the fracture site. The plate is slid adjacent to the bone
      in an epiperiosteal tunnel connecting the two insertional incisions. Screws are
      placed in the plate through the insertional incisions or via additional stab
      incisions made over the holes in the plate. In this paper we describe the
      surgical approaches used to perform MIPO in humeral, radial, femoral and tibial
      fractures in dogs. We found that these approaches allowed safe insertion of the
      plate without grossly damaging neuro-vascular structures. Further studies are
      needed to evaluate the clinical outcome of MIPO in dogs.

PMID- 19597636
TI  - Feline shoulder arthroscopy using a caudolateral portal, a cadaveric study.
AB  - The aim of this cadaveric study was to determine the normal arthroscopic anatomy
      of the feline shoulder from a caudolateral arthroscope portal, to compare this
      with the gross anatomy evident upon dissection, and to determine the degree of
      iatrogenic trauma caused by the arthroscopy. A 1.9 mm, 30 degrees fore oblique
      arthroscope via a caudolateral portal, and a 21-gauge needle via a craniolateral
      egress portal were used to assess intra-articular structures in eight feline
      cadaveric shoulders. The medial glenohumeral ligament was shown to be a single
      banded structure in the craniomedial compartment, and the subscapularis muscle
      tendon of insertion was visible in all eight shoulders. The biceps brachii tendon
      and sheath could be examined, although the transverse humeral ligament was not
      evident arthroscopically from this portal. The lateral glenohumeral ligament was
      not demonstrated arthroscopically, although a well-defined capsular thickening
      was present on dissection. No significant neurovascular trauma was evident after
      arthroscopy.

PMID- 19597637
TI  - Traumatic fragmented medial coronoid process in a Chihuahua.
AB  - Fragmented medial coronoid process (FMCP) is a disease process that has not
      previously been reported in toy-breed dogs. This report describes a presumptive
      case of FMCP in a 14-month-old Chihuahua that was presented for evaluation
      approximately four weeks following acute onset of moderate lameness in the left
      forelimb. Definitive diagnosis of a fragmented medial coronoid process was based
      upon computed tomography (CT) scan. A CT scan also demonstrated moderate joint
      incongruity in the affected elbow. Surgical removal of the fragment and subtotal
      coronoidectomy were performed via a medial arthrotomy. An ulnar ostectomy was
      also performed to address joint incongruity. Histology of specimens removed at
      surgery did not demonstrate evidence of microdamage as characteristic of FMCP in
      large breed dogs, and instead, suggested that the fracture was acute and
      traumatic in nature. Rapid return to function was observed following surgery.

PMID- 19597638
TI  - Conservative management for complete loss of a metatarsal pad in a dog.
AB  - A three-year-old intact, male Siberian Husky was presented for complete loss of
      its left metatarsal pad. The wound was managed as an open wound and left to be
      closed by second intention healing. Conservative management consisted of regular
      lavage and bandage changes along with oral antibiotic administration and exercise
      restriction. Thirty days after referral conservative management was discontinued,
      as the wound was closed with minimal scar tissue formation and the dog was
      allowed to take walks wearing a protective boot for another month. The animal was
      then allowed to return to its previous activity. Four years of follow-up did not
      reveal any signs of lameness.

PMID- 19597639
TI  - Tibial plateau levelling osteotomy in an alpaca.
AB  - In this report, a case of cranial cruciate ligament (CrCL) rupture treated by
      tibial plateau levelling osteotomy (TPLO), in a 36-month-old male breeding
      alpaca, is described. The alpaca was presented with the complaint of acute onset
      of right pelvic limb lameness. The findings of our clinical and radiographic
      examinations were consistent with CrCL insufficiency of the right stifle joint.
      The right tibial plateau angle measured prior to surgery was 19 degrees . A TPLO
      was performed and this eliminated cranial tibial thrust. Culture of a swab taken
      from the surgical site prior to wound closure was positive for Pseudomonas
      aeruginosa . Enrofloxacin was administered parenterally for two weeks
      postoperatively. There were not any clinical signs of infection noted. Outcome
      assessments included veterinary examination (two and six weeks) and owner
      assessment (28 months). At two weeks the animal walked with a grade 2/5 lameness,
      and at six weeks radiographic examination showed progression of bone healing at
      the site of tibial osteotomy. A return to full breeding fitness occurred by eight
      weeks after the surgery. The alpaca remained free from lameness 28 months later,
      according to the owner.

PMID- 19597640
TI  - Human papillomavirus, genital warts, and vaccines.
AB  - Human papillomavirus (HPV)-related diseases, including cancers, low-grade
      neoplasia, genital warts, and recurrent respiratory papillomatosis, have a
      substantial impact on public health. The increasing incidence of HPV infection
      and genital warts highlights the need for an effective strategy for the
      management of this disease. Immunization holds the promise of reducing the
      overall burden of clinical HPV-related diseases. A prophylactic quadrivalent HPV
      6/11/16/18 vaccine is highly effective for reducing the risk of HPV 6-, 11-, 16-,
      and 18-associated cervical cancer, precancerous cervical lesions, and external
      genital lesions, including genital warts.

PMID- 19597641
TI  - Induction of resistance to respiratory tract infection with Klebsiella pneumoniae
      in mice fed on a diet supplemented with tulsi (Ocimum sanctum) and clove (Syzgium
      aromaticum) oils.
AB  - BACKGROUND AND PURPOSE: The impact of diet and specific food groups on
      respiratory tract infections has been widely recognized in recent years. This
      study was conducted to study the effect of tulsi (Ocimum sanctum) oil and clove
      (Syzgium aromaticum) oil on the susceptibility of experimental mice to
      respiratory tract infection. METHODS: The effect of 2 different regimens of short
      term (15 days) and long-term (30 days) feeding with tulsi oil and clove oil on
      the course of Klebsiella pneumoniae American Type Culture Collection 43816
      infection in the lungs of mice was analyzed. The operative mechanisms of lipid
      peroxidation/nitrite production were studied by estimating their levels in
      bronchoalveolar lavage fluid (BALF). Bacterial colonization, malondialdehyde
      (MDA) and nitrite production in BALF, and tumor necrosis factor-alpha level in
      serum were assessed. RESULTS: The results showed that there was a significant
      decrease in bacterial colonization after short-term feeding with clove oil
      compared with the controls (p < 0.05). For tulsi oil-fed mice, the decrease in
      bacterial load was significant with long-term feeding (p < 0.01). The maximum
      decrease in MDA levels and increase in nitrite levels were noted with long-term
      feeding. CONCLUSION: Dietary supplementation with tulsi and clove oils protects
      against bacterial colonization of the lungs.

PMID- 19597642
TI  - Outbreak of influenza A and B among military recruits: evidence from viral
      culture and polymerase chain reaction.
AB  - BACKGROUND AND PURPOSE: Influenza is an important cause of acute respiratory
      illness among military recruits, and pneumonia is the most frequent complication.
      This study was performed to categorize the clinical manifestations of influenza
      infections among military recruits. METHODS: In this retrospective chart review,
      epidemiologic investigation of patients who met the definitions of acute
      respiratory illness, influenza-like illness, and pneumonia was conducted.
      Surveillance of influenza by viral culture and polymerase chain reaction was
      performed weekly from a random selection of 4 patients with influenza-like
      illness of less than 3 days duration. RESULTS: 2074 and 2046 men recruited to the
      Substitute Service Training Center in Taiwan, from November 30 to December 31,
      2006 (outbreak 1), and January 11 to February 12, 2007 (outbreak 2), respectively
      were enrolled. During outbreak 2, 1182 men (57.7%) were identified to have acute
      respiratory illness, including 607 (29.6%) with influenza-like illness and 19
      (0.9%) with pneumonia. During outbreaks 1 and 2, sixty two nasal and throat swabs
      were obtained, 15 of which were influenza A and 6 were influenza B. All the
      influenza A isolates were A/Wisconsin/67(H3N2) viruses. Haemophilus influenzae
      was isolated from 9 of 19 patients with pneumonia (47.3%); 8 from sputum
      specimens and 1 from a blood specimen. H. influenzae was the primary identifiable
      bacterium. CONCLUSIONS: The 2 outbreaks consisted of concurrent infection of
      influenza A and B, with subsequent pneumonia. These results have implications for
      outbreak management and treatment of influenza among military recruits.
      Surveillance of influenza-like illness enables early detection of an outbreak and
      better understanding of the epidemiology of influenza in this setting.

PMID- 19597643
TI  - Hepatitis B virus and hepatitis C virus dual infection among patients with
      chronic liver disease.
AB  - BACKGROUND AND PURPOSE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual
      infection accounts for a substantial proportion of liver diseases worldwide.
      Although the exact prevalence is not known, these viral infections are common
      among patients with chronic liver disease (CLD). This study was performed to
      determine the prevalence of HBV and HCV dual infection among patients with CLD in
      Chennai, India. METHODS: 251 patients were tested for the presence of hepatitis B
      surface antigen (HBsAg), immunoglobulin (Ig)-M/IgG antibody to hepatitis B core
      antigen (anti-HBc) and anti-HCV antibodies, and HBV-DNA and HCV-RNA by
      qualitative polymerase chain reaction. RESULTS: Coinfection with HCV and HBV was
      detected in 15 patients (5.9%), 12 of whom (80.0%) were positive for HCV-RNA and
      IgG anti-HBc with no evidence of HBV-DNA, while 3 HBsAg-negative patients (20.0%)
      were positive for HBV-DNA in addition to HCV-RNA. Liver function test profiles
      were significantly altered for HCV-positive patients compared with HBV-positive
      and HBV/HCV coinfected patients (p = 0.001). Bilirubin and alanine
      aminotransferase levels were significantly raised in coinfected patients compared
      with non-HBV, non-HCV patients (p = 0.001). CONCLUSIONS: The results demonstrated
      that HBV was predominantly associated with underlying CLD among this group of
      patients in India and suggest that HBV coinfection in HCV-infected patients
      should not be excluded by negative HBsAg status alone.

PMID- 19597645
TI  - Protection with bacteriophage KO1 against fatal Klebsiella pneumoniae-induced
      burn wound infection in mice.
AB  - BACKGROUND AND PURPOSE: Bacteriophages, viruses that cause lysis of bacteria, can
      serve as an effective tool for the control of infections, especially those caused
      by multiple drug-resistant organisms. Klebsiella pneumoniae is one of the most
      predominant pathogens associated with burn wound infections, causing considerable
      morbidity and mortality. This study investigated the protective effect of K.
      pneumoniae-specific bacteriophage KO1 isolated from the environment in a mouse
      model of burn wound infection induced by K. pneumoniae. METHODS: The toxicity of
      the bacteriophage and its in vivo survival and stability in mice was assessed.
      The fatal dose of K. pneumoniae was ascertained in third-degree burn wound
      infection. The protective effect of the bacteriophage administered via the
      subcutaneous or intraperitoneal route was investigated. RESULTS: A substantial
      decrease in the bacterial load of blood, peritoneal lavage, and lung tissue was
      noted following treatment with the bacteriophage preparation. The decrease in
      microbial count was evident when the bacteriophage was administered either via
      the subcutaneous or intraperitoneal route. CONCLUSION: These results suggest that
      bacteriophages have the potential to modulate the course of burn wound infection
      caused by K. pneumoniae.

PMID- 19597644
TI  - Resistance to extended-spectrum beta-lactams by the emergence of SHV-12 and the
      loss of OmpK35 in Klebsiella pneumoniae and Escherichia coli in Malaysia.
AB  - BACKGROUND AND PURPOSE: In addition to beta-lactamase production, loss of porins
      confers resistance to extended-spectrum beta-lactams in Klebsiella pneumoniae and
      Escherichia coli infection. This study describes the detection of SHV-12 extended
      spectrum beta-lactamase (ESBL) subtype and the loss of OmpK35 porin in 4 strains
      of K. pneumoniae and E. coli. METHODS: Isoelectric focusing was performed to
      detect beta-lactamases in 4 strains of K. pneumoniae and E. coli. The presence of
      the SHV gene in the 4 isolates was characterized by polymerase chain reaction,
      DNA sequencing, and DNA hybridization. Loss of porin in these strains was
      analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western
      blot analysis. RESULTS: The strains of K. pneumoniae and E. coli were confirmed
      to be ESBL producers and were resistant to cefoxitin, with minimal inhibitory
      concentration values of 512 microg/mL. All 4 strains had beta-lactamases with an
      isoelectric value of 8.2. The SHV gene from these strains was characterized to be
      the SHV-12 subtype and was plasmid-borne. The deduced amino acid sequence showed
      that the SHV-12 beta-lactamase was a derivative of the more common ESBL, SHV-5
      subtype. All the strains showed absence of the OmpK35 porin. CONCLUSION:
      Resistance of the strains towards extended-spectrum beta-lactams was a result of
      a dual-mechanism - the production of SHV-12 enzymes and loss of the OmpK35 porin.

PMID- 19597647
TI  - Disk diffusion test and E-test with enriched Mueller-Hinton agar for determining
      susceptibility of Candida species to voriconazole and fluconazole.
AB  - BACKGROUND AND PURPOSE: A simplified antifungal disk diffusion test using Mueller
      Hinton agar containing 2% glucose and methylene blue 5 microg/mL (GM-MH, Clinical
      and Laboratory Standards Institute [CLSI] M44-A) has proved to correlate well
      with the standard reference test. A new azole, voriconazole, has recently been
      approved for clinical therapy in Taiwan. This study investigated the reliability
      of the disk diffusion test with GM-MH agar and compared the results with those of
      the E-test using GM-MH agar to determine the voriconazole and fluconazole
      susceptibility of Candida isolates. METHODS: The antimicrobial susceptibility of
      Candida isolates were evaluated by E-test and disk diffusion test in accordance
      with the guidelines of the CLSI, and compared with the reference antifungal
      macrodilution susceptibility test (CLSI M27-A). RESULTS: The antifungal disk
      diffusion test and the E-test using GM-MH agar plate provided a sufficiently
      accurate, time-efficient, and cost-effective way to determine the susceptibility
      of 182 Candida spp. to voriconazole and fluconazole. There was a high correlation
      between the test results of the E-test using the GM-MH agar plate and those
      obtained by the reference antifungal macrodilution susceptibility test (CLSI M27
      A). The results of the E-test and those of the 1-microg voriconazole disk
      diffusion test on the GM-MH agar plate at 24 h had a high correlation. All the
      minimal inhibitory concentrations of voriconazole for all Candida spp. were <8
      microg/mL. The positive predictive value of the susceptible disk test of
      voriconazole on the GM-MH agar plate was 100% at 24 h for C. albicans and other
      Candida spp. CONCLUSION: The disk diffusion test and the E-test using the GM-MH
      agar plate can be performed quickly, simply, and cost-effectively, and are
      practicable methods for the initial testing of the susceptibility of Candida spp.
      to voriconazole and fluconazole.

PMID- 19597646
TI  - Cefepime monotherapy is as effective as ceftriaxone plus amikacin in pediatric
      patients with cancer and high-risk febrile neutropenia in a randomized
      comparison.
AB  - BACKGROUND AND PURPOSE: The empirical use of antibiotic therapy is widely
      accepted for patients with fever and neutropenia during cancer chemotherapy. The
      use of intravenous monotherapy with broad-spectrum antibiotics in patients at
      high risk for complications is an appropriate alternative. However, few data are
      available for pediatric patients. The aim of this study was to compare the
      efficacy and safety of cefepime (CFP) monotherapy with ceftriaxone plus amikacin
      (CFT+AK) in children and adolescents with febrile neutropenia (FN). METHODS: A
      prospective randomized open study of patients with lymphoma or leukemia who had
      fever and neutropenia during chemotherapy was conducted. Patients were randomized
      to receive CFP or CFT+AK. The randomization was based on number lists. RESULTS:
      Fifty seven patients with 125 episodes of fever and neutropenia were evaluated
      (CFP, 62 episodes; CFT+AK, 63 episodes). The mean neutrophil count at admission
      to hospital was 118.6 cells/mm(3) for patients in the CFP group and 107
      cells/mm(3) for patients in the CFT+AK group. The mean duration of neutropenia
      was 9 days for the CFP group and 8 days for the CFT+AK group. Analysis of only
      the first episodes for each patient showed that CFP treatment was successful for
      65.5% of episodes and CFT+AK was successful for 64.3% of episodes. The overall
      rates of success with modification were 90% for the CFP group and 89% for the
      CFT+AK group. No major treatment-emergent toxicity was reported. CONCLUSION:
      Monotherapy with CFP seems to be as effective and safe as CFT+AK for initial
      empirical therapy in children and adolescents with FN.

PMID- 19597648
TI  - Comparison of the clinical manifestations of infective endocarditis between
      elderly and young patients - a 3-year study.
AB  - BACKGROUND AND PURPOSE: Infective endocarditis (IE) is associated with high
      morbidity and mortality. This study investigated the clinical manifestations and
      outcomes of IE and compared them between old and young patients. METHODS: In this
      retrospective study, data for patients with IE who were treated from November 1,
      2003 to October 30, 2006 were collected. Patients were identified as having IE if
      they met the modified Duke criteria for definitive IE. RESULTS: Seventy two
      patients were included. The most common symptoms were fever (81%) and dyspnea
      (50%). Fifty four patients (75%) had culture-positive IE. Staphylococcus aureus
      (35%) was the most common organism isolated, followed by Streptococcus spp.
      (26%). Vegetations were detected in 60 patients (83%): mitral valve (MV; 40%),
      aortic valve (AV; 24%), tricuspid valve (TV; 14%), MV and AV (4%), and pulmonary
      valve (1%). Thirty nine patients (54%) had embolic complications - 26 older
      patients (79%) and 13 younger patients (33%). Twenty two patients (31%) died in
      hospital. There were significant differences in clinical features between older
      and younger patients. Diabetes mellitus (p <or= 0.01), MV vegetation (p <or=
      0.01), emboli (p <or= 0.01), and mortality (p = 0.01) were more common among
      older patients, while male sex (p <or= 0.01), intravenous drug use (p <or= 0.01),
      S. aureus endocarditis (p <or= 0.01), and TV vegetation (p = 0.01) were more
      common in younger patients. CONCLUSION: While this study showed significant
      differences between older and younger patients, further investigation will be
      necessary to more precisely characterize the clinical spectrum of IE.

PMID- 19597649
TI  - Microbiologic spectrum and susceptibility pattern of clinical isolates from the
      pediatric intensive care unit in a single medical center - 6 years' experience.
AB  - BACKGROUND AND PURPOSE: Nosocomial infection contributes to the morbidity and
      mortality of patients in hospital. Timely microbiologic surveillance and
      assessment of antimicrobial resistance is important for dealing with nosocomial
      infections. This retrospective review was conducted to evaluate the microbiologic
      spectrum and susceptibility pattern in the pediatric intensive care unit from
      2001 to 2006. METHODS: The microbiologic data and antimicrobial susceptibility of
      all clinical isolates in the pediatric intensive care unit between 2001 and 2006
      were reviewed. The incidence and distribution of nosocomial infections and the
      associated pathogens were also analyzed. RESULTS: 1163 clinical isolates were
      analyzed. The frequencies of Gram-positive and Gram-negative bacteria were 30.4%
      and 56.2%, respectively. Staphylococcus aureus was the most common isolate among
      the Gram-positive organisms, while Pseudomonas aeruginosa, Escherichia coli, and
      Klebsiella pneumoniae were the 3 leading Gram-negative isolates. The proportion
      of methicillin-resistant S. aureus (MRSA) to all S. aureus was 65.2%. Six
      vancomycin-resistant enterococci were isolated in 2003. Extended-spectrum beta
      lactamase (ESBL)-producing K. pneumoniae accounted for 20% of K. pneumoniae
      isolates since 2005. Carbapenem-resistant P. aeruginosa accounted for 34% of P.
      aeruginosa isolates. The nosocomial infection rate was not reduced after moving
      to a new hospital building in 2003. Urinary tract infection (30.2%) was the most
      common nosocomial infection, followed by bloodstream infection (26.5%) and lower
      respiratory tract infection (25.3%). CONCLUSIONS: MRSA, carbapenem-resistant P.
      aeruginosa, and ESBL-producing K. pneumoniae were the major concerns in this
      study. Good hand hygiene and strict aseptic procedures remain the most important
      factors for infection control.

PMID- 19597650
TI  - Subcutaneously implanted central venous access device infection in pediatric
      patients with cancer.
AB  - BACKGROUND AND PURPOSE: Subcutaneously implanted central venous access devices
      (SICVADs) are a common route of intravascular access for pediatric patients with
      cancer. This study was performed to evaluate the risk for SICVAD-related
      infection in a large consecutive series of unselected children with cancer in a
      single medical center. METHODS: The medical charts of 209 pediatric patients with
      cancer who received a SICVAD from January 1, 2001 to December 31, 2005 were
      retrospectively reviewed, and the patients were followed-up until June 30, 2006.
      The demographics, clinicopathologic features, and infectious complications were
      collected for analysis. RESULTS: There were 137,924 SICVAD days (median, 660
      days; range, 16-1962 days). The rate of SICVAD-related infections was 0.15
      episodes/1000 SICVAD days. There were 21 episodes of SICVAD-related infection
      among 17 patients, 18 were bloodstream infection among 14 patients and the other
      3 were local infection among 3 patients. Sixteen SICVADs were removed, 13 were
      associated with bloodstream infection and 3 with local infection. Young age (<2
      years) was associated with a high risk for SICVAD-related infection.
      Staphylococcal spp. and fungi were the most common pathogens associated with
      SICVADs. CONCLUSIONS: The rate of SICVAD-related infection in children with
      cancer was low. Children younger than 2 years had a higher risk for SICVAD
      related infection than older children. Fungi play an important role in SICVAD
      related infection.

PMID- 19597651
TI  - Effect of amino acids on tannase biosynthesis by Bacillus licheniformis KBR6.
AB  - BACKGROUND AND PURPOSE: Microbial tannase (tannin acyl hydrolase, EC 3.1.1.20), a
      hydrolysable tannin-degrading enzyme, has gained importance in various industrial
      processes, and is used extensively in the manufacture of instant tea, beer, wine,
      and gallic acid. Tannase is an inducible enzyme, and hydrolysable tannin,
      especially tannic acid, is the sole inducer. This study is of the effect of
      various amino acids and their analogues on tannase biosynthesis by Bacillus
      licheniformis KBR6 to ascertain the mode of action of these growth factors on
      tannase biosynthesis from microbial origin. METHODS: Enzyme production was
      carried out in enriched tannic acid medium through submerged fermentation for 20
      h at 35 degrees C. Different amino acids at a concentration of 0.05 g% (w/v) were
      added to the culture medium immediately after sterilization. Culture supernatant
      was used as the source of the enzyme and the quantity of tannase was estimated by
      the colorimetric assay method. Growth of the organism was estimated according to
      biomass dry weight. RESULTS: Maximum tannase (2.87-fold that of the control) was
      synthesized by B. licheniformis KBR6 when alanine was added to the culture
      medium. Other amino acids, such as DL-serine, L-cystine, glycine, L-ornithine,
      aspartic acid, L-glutamic acid, DL-valine, L-leucine and L-lysine, also induced
      tannase synthesis. L-Cysteine monohydrochloride and DL-threonine were the most
      potent inhibitors. CONCLUSIONS: Regulation of tannase biosynthesis by B.
      licheniformis in the presence of various amino acids is shown. This information
      will be helpful for formulating an enriched culture medium for industrial-scale
      tannase production.

PMID- 19597653
TI  - The social role of research in nursing.

PMID- 19597652
TI  - Complicated intra-abdominal infection caused by extended drug-resistant
      Achromobacter xylosoxidans.
AB  - Achromobacter xylosoxidans (formerly Alcaligenes xylosoxidans) is a rare but
      important nosocomial pathogen. Antibiotic resistance has been increasing during
      the past decade. A. xylosoxidans may be confused with Pseudomonas spp. but,
      unlike Pseudomonas spp., this organism has peritrichous flagella. Complicated
      intra-abdominal infection with A. xylosoxidans has rarely been reported in the
      literature. This report is of an immunocompetent patient with acute cholecystitis
      complicated by an intra-abdominal abscess after surgery. Culture of both blood
      and ascites yielded extended drug-resistant A. xylosoxidans, which was only
      sensitive to colistin. The clinical and laboratory characteristics of A.
      xylosoxidans are presented.

PMID- 19597654
TI  - [Frequent nursing diagnoses and interventions for women under critical care].
AB  - This study aimed at identifying the most frequent Nursing Diagnoses and propose
      interventions for women under critical care into a maternal intensive care unit
      in a public hospital in Fortaleza, CE, Brazil. Retrospective study conducted with
      women's hospital health records. Ten Nursing Diagnoses were elaborated, being
      four risk: risk of infection, risk of unbalance of liquids volume, risk of
      aspiration, risk of damaged skin integrity and six real: altered maternity,
      impaired physical mobility, anxiety and impaired verbal communication. For the
      referred Nursing Diagnoses, nursing interventions are proposed according to the
      link between NANDA, NIC and NOC. It was concluded that the use of ND is a
      necessary technology for the Nursing reality, as it makes possible the integral
      care.

PMID- 19597655
TI  - [Humanization of nursing care: what is it?].
AB  - The study was conducted with the purpose of identifying how nursing professionals
      understand the expression 'humanized care'. This is a qualitative research,
      accomplished according to the historic oral thematic method. Seven nurses of a
      major Sao Paulo hospital were chosen to partake on this study. According to the
      analysis and understanding of the meanings expressed on the different speeches it
      was possible to identify that the expression 'humanized care' has been used with
      the intension of expressing dehumanization, associated both with nursing
      professionals dehumanization, from the patient's perspective, and with
      dehumanization associated with the institution from the nursing professionals
      point of view. It was identified that this term has been used without the full
      understanding of its meaning.

PMID- 19597656
TI  - [The adolescent mother and the care of her child in the first week of life].
AB  - This study aims at understanding the experience of adolescent mothers in taking
      care of her child in the first week after birth by domiciliary accompaniment. Six
      adolescents participated, accompanied between February and October 2007. Data
      collection was accomplished through semi structured interviews and participant
      observation. Culture Care Diversity in Nursing Practice was adopted as
      theoretical reference. The results had disclosed that the experience of
      caretaking is lived deeply of diverse ways. For some of the adolescents care was
      developed with assurance; others were frightened and insecure and did not
      immediately take on. The mothers of the adolescents served as support, showing
      how to develop care, thus gradually inserting the daughters into practice, making
      them integrally assume the attention.

PMID- 19597657
TI  - [Continuing education in nursing: a methodological proposal].
AB  - The aim of this paper is to present a study on the Continuing Education Program
      of a Teaching Hospital in the city of Sao Paulo, aiming to raise subsidies for
      its improvement from an interdisciplinary point of view. Data were collected with
      the program coordinators by means of a semi-structured interview and the
      questionnaire consisted of open and multiple-choice questions applied to 100
      nurses into the Hospital. The results suggested some thoughts on the development
      of nursing educational processes, identifying challenges to be exceeded by the
      group. It was concluded that to change the nursing professional education into a
      continuous process, it must be considered the daily work as a support of the
      educational process, source of knowledge and object of transformation, which will
      favor a collective and interdisciplinary participation.

PMID- 19597658
TI  - [Healthcare needs of the aged: perspectives for nursing].
AB  - This study has as central thematic the healthcare need of the aged. It was
      established as aims: to understand the expectations of the aged one who
      experiences nursing actions in primary health care and to point out at healthcare
      need of the aged one in this context. It was developed through the theoretical
      and methodological approach of the phenomenological sociology of Alfred Schutz.
      It was used a phenomenology interview with aged persons having as question: which
      are your expectations about the nursing professionals? Two lived categories
      emerged: to find the other (human) in the nursing professional attitude and to
      establish relationships with other persons. The study points out at the
      importance of the named none-technical nursing actions as health needs.

PMID- 19597659
TI  - [Feminine group of care: research-care strategy to the woman].
AB  - Qualitative research that aimed at implementing a Discussion Group that could be
      research strategy and woman assistance. The subjects were eighteen women from a
      Health Unit. The method was the convergent and assistance research. The thematic
      analyzes was applied to the generated content from the discussion. The results
      indicated that the women referred the strategy of the Group establishing the
      dialogue, hearing their own voices and the other's, developing the self
      perception about the learning in the co-construction of the knowledge that
      contributes to the self-care. The Discussion Group had configured itself as
      opportunity and stimulation of the clientele in the fortification of the health
      promotion.

PMID- 19597660
TI  - [Understanding care dimensions in an emergency hospital unit].
AB  - The objective of this qualitative study was to comprehend the meaning of the
      nursing care relationships in an emergency unit from the perception of the human
      receiving care and to provide theoretical subsidies in order to think about the
      care relationships established in day-to-day nursing work. Nineteen (19) subjects
      were interviewed in an emergency hospital unit in Santa Catarina, Brazil. The
      data was submitted to content analysis and interpreted according to complex
      thought. The care dimensions, presented in six categories, mobilize and
      articulate the multiple human competencies and techniques of/by caring beings in
      the comprehension of the nursing care process, from the perspective of those who
      receive care, including rethinking nursing practice itself and the multiple
      conditions of the environment as a space for care.

PMID- 19597661
TI  - [The dimensions of prenatal care embodied in nursing consultation].
AB  - This study aimed at analyzing the social representation of pregnant women about
      pregnancy, regarding care provided in nursing consultations during the prenatal
      period. A qualitative study conducted by semi-structured interviews, with fifteen
      pregnant women at the nursing consultations of the prenatal program regarding the
      care provided, analyzed by the ALCEST software. Three thematic axes were
      identified: the experience of pregnancy, constituted by the classes: the impact
      and the changes due to pregnancy; the orientations provided about pregnancy, with
      the classes: perception of the nursing consultation and family planning; and the
      approaches baby care, with the classes: how to take care of the new-born and how
      to assure good breastfeeding. A nursing consultation covers different dimensions
      psychosocial to pregnancy and to the newborn.

PMID- 19597662
TI  - [Determinatives of the tension of the dependent elderly's family caregiver].
AB  - This study had as objective investigate the determinatives of the tension of the
      dependent elderly's family caregiver. Its accomplish happened in the domestic
      scenery, involving thirty principal caregivers. The data were collected by a
      recorded and structured interview. The analyses of the objective data was made by
      means of a quantitative approach. The discursive data, for being collected
      through a structured instrument, dispensed analytic procedure, being distribute
      between questions that referee in the way of amply your comprehension. The
      results appoint that the investigated phenomenon starts from determinatives
      related to the caregiver, to the elderly's deficits, to the interection
      elderly/caregiver, to the environment, and related to the care demands.

PMID- 19597663
TI  - [The trajectory of a nurse: Neuza Aparecida Ramos].
AB  - This historical-social study aims at: contributing to the data bank of the
      Historical-Cultural Center of Iberian-American Nursing through incorporating
      another recorded interview with a nurse as well as rescuing a portion of the
      State of Parana Nursing History; and helping in its dissemination. Life oral
      history was utilized as this has facilitated to know the trajectory followed by
      the nurse Neuza Aparecida Ramos, as a person and as a professional. Her life oral
      history was collected through an interview which has captured her living and
      working experiences as well as her leadership in the educational field. Data
      collected were classified into the following categories: professional trajectory,
      the work in Curitiba, carried out activities, challenges, assignments received
      and her personal vision on the future of the profession. This paper has allowed
      to rescue the life history of an ocular witness of important facts of the
      Brazilian Nursing History and that of Parana.

PMID- 19597664
TI  - [The genogram and the eco-map in family health nursing care].
AB  - The nursing needs to observe the importance of the family, because if the family
      is present and oriented for cared, it contributes more effectively to the healthy
      life of its members. The study aimed at learning the coping behaviour of six
      families with chronic diseases, through three home visits, using interviews, form
      of identification, genogram and eco-map. In general, families face satisfactorily
      the chronic stress situations. It was needed to full fill the difficult task of
      exercising the broader view, required the nurse to understand that the process of
      work is not restricted to acting on diseases and disorders, but give the family
      conditions to earn health in all its dimensions.

PMID- 19597665
TI  - [The education in graduate nursing in the State of Parana, Brazil].
AB  - We approach the implementation of the Curricular Guidelines of degree in nursing
      in Parana identifying the curricular changes triggered, analyzing changes made
      and identifying pedagogical principles that were effectively materialized with
      the new proposals. We found a growth around 80% of private courses/schools of
      nursing. We analyze 9 political pedagogical projects showing that some courses
      have their own constructions from the curricular guidelines. Others are suited to
      them literally. The data relating to education focused on the student; the role
      of the professor; the pedagogy of skills; the learning to learn; the Unified
      Health System as a focus of the training; a licenciature/education in nursing;
      the research in the graduation; the times in training and the methodological
      approach of the course testify this assertion.

PMID- 19597666
TI  - [Do the practices developed in Family Health Program contribute to transform the
      present model of health care].
AB  - This study aimed to identify and analyze the main primary health care practices
      developed in the Family Health Care Program. Qualitative case study was carried
      out in the region of Sao Sebastiao, DF. Data were collected through semi
      structured interviews with team workers and observation of the work process. The
      author concluded that diverse basic practices are developed in primary health
      care, but others practices focused in health care promotion are necessary in
      order to transform the health care model.

PMID- 19597667
TI  - [Promoting citizenship through nursing care].
AB  - This study is the result of the project: networks care and social
      entrepreneurship: the autonomy and social commitment of nurses. The purpose of
      this qualitative study is to comprehend the meaning of nursing care as a social
      enterprising practice. The Grounded Theory was used as a methodological reference
      and the interview, conducted with 35 participants as technique of data
      collection. Data codification led to the central theme: Viewing Nursing Care as a
      Social Enterprising Practice. This theme is complemented by the category,
      characterized the cause condition: the social integration through the creation a
      political identity that expresses your involvement. The results showed that is
      necessary to learn and have a deep dialogic knowledge. In order to consolidate
      popular participation as a citizenship ideal, a critical professional attitude,
      base don the combination of care with liberty, participation end autonomy.

PMID- 19597668
TI  - [Vital signs and facial expression of patients in coma].
AB  - The objective was to check music and voice message influence on the vital signals
      and facial expressions of patients in physiological or induced comas. A
      randomized controlled clinical trial was done. The sample was consisted of 30
      patients from Intensive Care Unit, being divided in 2 groups: Group Control
      (without auditory stimuli) and Experimental Group (with auditory stimuli). The
      patients were submitted to 3 sessions for consecutive days. Significant
      statistical alterations of the vital signs were noted (oxygen saturation -
      session 1; oxygen saturation - session 3; respiratory frequency - session 3)
      during the message playback and with facial expression, session 1, during both
      music and message. Apparently, the voice message is a stronger stimulus than the
      music in relation to the capacity of producing suggestive physiological auditory
      responses.

PMID- 19597669
TI  - [Ethnonursing as research methodology for the congruence of care].
AB  - Etnonursing, as a research methodology, is applied to approach the cultural
      context and of care in health of one specific culture. Aiming at demonstrating
      the process of application of this methodology in nursing, from what is proposed
      by Leininger, four steps of observation are presented, one of interview and for
      steps of analysis of data, covering specific and congruent criteria with the
      qualitative paradigm. These steps are not isolated, they relate to one another in
      an intricate way. It is considered that the knowledge produced can contribute
      largely for the subjects of the research as well as for the practice of the
      health workers, developing nursing as a science and providing new paths for the
      health care, for performing their jobs, through ethics, diversity of workers;
      complementing the theory of Leininger.

PMID- 19597670
TI  - [Information systems supporting the management work in health].
AB  - The article presents some aspects on the relevance of the information systems as
      tool of support to the management of the work of the health professionals, a time
      that is a computational resource capable to potential the knowledge search. Know
      that the information systems available of fast form, easy and insurance the
      information, allowing that the professionals of the health search knowledge and
      if become able, creative and competent to inside act with the complexity of the
      work in health of the Brazilian system of health aiming at to consolidate the
      politics of the National Health System. It is reflected on what it is the
      management of the work in health and as the information systems they come
      contribute for the fortify of action and processes of health in this area.

PMID- 19597671
TI  - [Nurses' speeches on death and to die: truth or will].
AB  - We consider looking at the death and dying as a social, historical and cultural
      construction. Thus, in we approach them to the Cultural Studies to know nurses
      speeches on the subject. The research is periodic articles of two national ones
      of nursing. In the analyses we use tools proposals for Michel Foucault that they
      make possible to constitute four categories: the silenced and occulted death;
      stopping one it fights against the death; the death in scene: multiplicity of
      faces and the palliative death and cares: paradigm change. The study detaches the
      way as the publications operate in the production of knowing on the death and
      dying to them and subjectiving the nurses.

PMID- 19597672
TI  - [Treatment of open wounds using Mosqueta Rose: a review].
AB  - This article is about a literature revision concerning to the main published
      scientific works in the last two decades about the medicinal properties of the
      Mosqueta Rose, especially in the treatment of open wounds. The objective is to
      congregate information demonstrating, by means of scientific and empirical
      evidences, the importance of the traditional medicine related to the use of the
      Mosqueta Rose in many clinical applications. This study is characterized as a
      compilation of significant information about the composition, indications and
      empirical uses of the extract of Mosqueta Rose, in order to make easier posterior
      researches, since the production about this subject is scarce. The
      bibliographical research was carried through the data base Bireme, SciELO, Capes
      and sites related to the subject in the Internet.

PMID- 19597673
TI  - [Incubate of learning in nursing: an innovation in teaching the care].
AB  - This study had as objective to reflect about incubate of learning in the nursing
      as an innovation in the teaching of the care. The incubate can be considered a
      strategy to create conditions for the incubation, the development of innovative
      ideas and the wakening of new enterprising ideas for the growth up of people,
      businesses and institutions. When using the critical, reflective thought
      associated when making in nursing, propitious environment, the incubate points
      with respect to methodological innovation at learning of the care.

PMID- 19597674
TI  - [The teaching of oncology in nurse's education].
AB  - The aim of the present study was to think the Oncology Course in the
      baccalaureate nursing curriculum pointing relevant issues about its introduction,
      considering professional training and qualification, labor market demand and a
      critical reflection about nurse's professional competences. Score is also the
      role of technology in helping training and education of new health professionals.

PMID- 19597675
TI  - [The Brazilian Nursing Congress: sixty years of history].
AB  - This study objective is to describe the issues associated to the origin of the
      Brazilian Nursing Congress and its course between 1947 and 2007; and to discuss
      the implementation of this strategy by the Brazilian Nursing Association (ABEn).
      It is a historical survey with documentary research. The documentary analysis
      allowed reaching the following categories: the origin of the Brazilian Nursing
      Congress and the congresses as the political nursing arena. We have concluded
      that the Brazilian Nursing Congresses have reflected the construction of the
      Brazilian Nursing history, aiming at stimulating the critical consideration on
      the professional problems and investing in the production of knowledge,
      addressing the growing complexity and quality of the professional practice.

PMID- 19597676
TI  - [Eating act and people with Down Syndrome].
AB  - This is en experience report lived in the Health and Nursing Assistance Projects
      of the Post-Graduate Nursing Master Degree of the Federal University of Santa
      Catarina as an interdisciplinary subject, and it was done with Down's Syndrome
      people, concentrating in their rationality and imaginary. We tried to build with
      these people and their families an individualized nutritional systematization
      that contributes to their personal independence in the daily practice of the act
      of eating. The postulates of symbolic interactionism guided this practice and
      established a connection with the methodological instruments of sensible
      listening and observation, besides playful activities. It was evident that the
      first meaning of the act of eating is built in the family and reinforced in the
      social life.

PMID- 19597678
TI  - Evidence-based health technology assessments for the Brazilian National Health
      System (Sistema Unico de Saude, SUS) and for all.

PMID- 19597679
TI  - Screening, diagnosing and treating deafness: the knowledge and conduct of doctors
      serving in neonatology and/or pediatrics in a tertiary teaching hospital.
AB  - CONTEXT AND OBJECTIVE: Infant hearing deficiency is a human disorder with
      devastating effects and serious implications for the development of speech and
      language. Early diagnosis of hearing loss should be the objective of a
      multidisciplinary team, and early-intervention programs should immediately follow
      this. The aim of this study was to investigate the knowledge and conduct of
      pediatricians and pediatric residents in a tertiary teaching hospital regarding
      deafness. DESIGN AND SETTING: Cross-sectional study in a tertiary hospital in the
      state of Sao Paulo, Brazil. METHODS: Eighty-eight questionnaires were randomly
      distributed to pediatricians and pediatric residents. RESULTS: Thirty-six
      questionnaires were analyzed. Most respondents (61.1%) were residents in
      pediatrics and/or neonatology. Eighty-three percent of them performed special
      procedures on babies presenting a high risk of deafness, and 55% reported that
      they had no knowledge of techniques for screening hearing. Most of them were
      unaware of the classifications of level and type of hearing loss. According to
      47.2% of them, infants could begin to use a hearing aid at six months of age.
      Most of them reported that infants could undergo hearing rehabilitation during
      the first six months of life, and all respondents stated 's responsibilities.
      CONCLUSIONS: Even though most of the participants followed special procedures
      with babies presenting a high risk of deafness, they did not routinely
      investigate hearing. All respondents believed that it is a doctor's
      responsibility to be concerned about child communication.

PMID- 19597680
TI  - Prevalence of c-myc expression in breast lesions associated with
      microcalcifications detected by routine mammography.
AB  - CONTEXT AND OBJECTIVE: Genetic abnormalities in cell proliferation-regulating
      genes have been described in premalignant lesions. The aims here were to evaluate
      c-myc protein expression in non-palpable breast lesions associated with
      microcalcifications, detected by screening mammography, and to compare these
      results with histopathological, clinical and epidemiological variables. DESIGN
      AND SETTING: Analytical cross-sectional study, with retrospective data
      collection, in a university hospital in Sao Paulo. METHODS: Seventy-nine female
      patients who underwent routine mammography between 1998 and 2004 were studied.
      Lesions classified by the Breast Imaging Reporting and Data System (BI-RADS) as 4
      or 5 underwent percutaneous biopsy using a large-core needle. Ninety-eight
      lesions were studied anatomopathologically. Paraffin blocks properly representing
      the lesions were selected for immunohistochemical analyses using the streptavidin
      biotin-peroxidase technique with monoclonal mouse c-myc antibodies. RESULTS:
      Among the 98 lesions, 29 (29.6%) contained malignant neoplasia; 40 (40.8%) had a
      positive immunohistochemical reaction for c-myc. When the groups were divided
      between lesions without atypias versus atypical lesions plus malignant lesions,
      31.03% of the 58 lesions without atypias were positive for c-myc and 55% of the
      40 malignant and atypical lesions (P = 0.018). Comparing the atypical lesions
      with ductal carcinoma in situ versus the benign lesions without atypias, c-myc
      was present in 51.61% of the 31 atypical lesions and 31.03% of the benign lesions
      without atypias (P = 0.057). CONCLUSION: C-myc protein was more frequently
      expressed in atypical and malignant lesions than in benign lesions without
      atypias. C-myc expression correlated with the presence of atypias (P = 0.018).

PMID- 19597681
TI  - Prevalence of radiological findings among cases of severe secondary
      hyperparathyroidism.
AB  - CONTEXT AND OBJECTIVE: Patients with end stage renal disease (ESRD) and secondary
      hyperparathyroidism (HPT2) are prone to develop heterotopic calcifications and
      severe bone disease. Determination of the sites most commonly affected would
      decrease costs and patients' exposure to X-ray radiation. The aim here was to
      determine which skeletal sites produce most radiographic findings, in order to
      evaluate hemodialysis patients with HPT2, and to describe the most prevalent
      radiographic findings. DESIGN AND SETTING: This study was cross-sectional,
      conducted in one center, the Hospital Universitario Clementino Fraga Filho
      (HUCFF), in Rio de Janeiro, Brazil. METHODS: Whole-body radiographs were obtained
      from 73 chronic hemodialysis patients with indications for parathyroidectomy due
      to severe HPT2. The regions studied were the skull, hands, wrists, clavicles,
      thoracic and lumbar column, long bones and pelvis. All the radiographs were
      analyzed by the same two radiologists, with great experience in bone disease
      interpretation. RESULTS: The most common abnormality was subperiosteal bone
      resorption, mostly at the phalanges and distal clavicles (94% of patients, each).
      'Rugger jersey spine' sign was found in 27%. Pathological fractures and
      deformities were seen in 27% and 33%, respectively. Calcifications were presented
      in 80%, mostly at the forearm fistula (42%), abdominal aorta and lower limb
      arteries (35% each). Brown tumors were present in 37% of the patients, mostly on
      the face and lower limbs (9% each). CONCLUSION: The greatest prevalence of bone
      findings were found on radiographs of the hands, wrists, lateral view of the
      thoracic and lumbar columns and femurs. The most prevalent findings were bone
      resorption and ectopic calcifications.

PMID- 19597682
TI  - Prevalence of reduced respiratory muscle strength in institutionalized elderly
      people.
AB  - CONTEXT AND OBJECTIVES: Respiratory muscle strength is relevant to the clinical
      situation of elderly patients, particularly those presenting with respiratory or
      cardiac diseases. The objectives of this study were to evaluate the respiratory
      muscle strength of institutionalized elderly women, compare this with predicted
      values for the Brazilian population and calculate the correlation with age and
      anthropometric characteristics. DESIGN AND SETTING: Cross-sectional study at the
      Department of Physiotherapy of Universidade Camilo Castelo Branco. METHODS: The
      participants were 56 institutionalized elderly women (74.87 +/- 10.55 years of
      age), evaluated in eight institutions in three cities in the central region of
      the State of Sao Paulo, between January 2005 and March 2006. They were separated
      into three subgroups according to age: 60-69 years (n = 20), 70-79 (n = 18) and
      80-89 years (n = 18). Maximal respiratory pressures were obtained using a
      manovacuometer. The values obtained were compared between subgroups and with
      predicted values. Correlation analysis was used to evaluate age, weight, height
      and body mass index in relation to maximal respiratory pressures. The
      significance level was P < 0.05. RESULTS: No significant differences in maximal
      respiratory pressures were seen between the three subgroups. The maximal
      respiratory pressures were significantly lower in the three subgroups, compared
      with predicted values. Negative correlations between maximal respiratory
      pressures and age and positive correlations in relation to weight, height and
      body mass index were found. CONCLUSIONS: Respiratory muscle strength was markedly
      reduced in institutionalized 60 to 89-year-old women and the values demonstrated
      correlations with age and anthropometric characteristics.

PMID- 19597684
TI  - Mullerian duct anomalies: review of current management.
AB  - The aim of this paper was to discuss the embryological aspects of Mullerian duct
      anomalies and to analyze the current diagnostic methods and therapy. Mullerian
      anomalies are congenital defects of the female reproductive tract resulting from
      failure in the development of the Mullerian ducts and their associated
      structures. Their cause has yet to be fully clarified, and it is currently
      believed to be multifactorial. Symptoms appear principally during adolescence or
      early adulthood, and affect the reproductive capacity of these women. When
      clinically suspected, investigations leading to diagnosis include imaging methods
      such as hysterosalpingography, ultrasonography and magnetic resonance. The
      classification of these malformations relates to their embryogenesis, and defines
      the therapy and prognosis. Mullerian anomalies consist of a wide range of defects
      that may vary from patient to patient. Therefore, their management must also be
      individual, taking anatomical and clinical characteristics into consideration, as
      well as the patient's wishes.

PMID- 19597683
TI  - Bevacizumab for ocular neovascular diseases: a systematic review.
AB  - CONTEXT AND OBJECTIVE: Many eye diseases involve increased local levels of
      vascular endothelial growth factor (VEGF), and there are several therapeutic
      strategies for them. Thus, the aim of this study was to evaluate the
      effectiveness and safety of bevacizumab for treating eye diseases involving
      increased local levels of VEGF, as the assumed pathophysiological mechanism. DATA
      SOURCES: The following databases were systematically searched for evidence:
      PubMed, CENTRAL (Cochrane Library), Literatura Latino-Americana e do Caribe em
      Ciencias da Saude (Lilacs) and reference lists, without language restrictions.
      Only randomized controlled trials were included. The primary outcome of interest
      was visual acuity, irrespective of the evaluation method. DATA SYNTHESIS: A total
      of 667 eyes in nine randomized trials were included. Meta-analysis showed that
      the proportion of patients with age-related macular degeneration who presented
      improvements from baseline regarding best-corrected visual acuity was higher
      among those treated with bevacizumab than among those in the photodynamic therapy
      group (risk ratio, RR, 0.49; 95% confidence interval, CI, 0.31 to 0.78; P =
      0.01). CONCLUSIONS: The evidence available demonstrates that bevacizumab alone or
      combined with other treatments is more effective than other options, including
      photodynamic therapy, focal photocoagulation and triamcinolone. The use of
      bevacizumab instead of photodynamic therapy could reduce treatment costs by more
      than 99% and could significantly increase access to treatment. However, long-term
      studies are still needed in order to reduce uncertainty concerning the safety of
      this medication for all ocular neovascular diseases in which bevacizumab has the
      potential to improve visual acuity.

PMID- 19597686
TI  - Medical learning in a private hospital: patients' and companions' perspectives.
AB  - CONTEXT AND OBJECTIVE: Contact with patients has important implications for
      medical students' education. Previous studies have shown that patients in
      teaching hospitals have positive views about medical education. The aim here was
      to assess the acceptability of medical education among patients and their
      companions in a non-teaching private hospital that is planning to implement a
      medical teaching program in the near future. DESIGN AND SETTING: Cross-sectional
      study conducted in a 200-bed tertiary-care private hospital in Brasilia. METHODS:
      Between March and April 2005, patients and their companions in three different
      sections of the hospital (intensive care unit, ward and emergency waiting room)
      were surveyed using a questionnaire. RESULTS: The questionnaire was completed by
      209 volunteers. The majority of the volunteers (178; 85%) said that they would
      allow a student to be present during consultations. Of these, 102 (57%) said that
      they would like to have a student present. Acceptance of the presence of students
      was higher among males (males 93%; females 81%; P = 0.026). Intensive care unit
      respondents said that they would like medical students to be present more
      frequently than the other two groups said this (ward 48%; emergency room 49%;
      intensive care unit 74%; P = 0.011). CONCLUSIONS: Not only were medical students
      well accepted but also their presence during consultations was desired by many
      patients and their companions. These findings may be of great value for plans to
      implement medical teaching programs in private hospitals.

PMID- 19597685
TI  - Artificial oxygen carriers as a possible alternative to red cells in clinical
      practice.
AB  - Fluid resuscitation is intended to eliminate microcirculatory disorders and
      restore adequate tissue oxygenation. The safety limits for a restrictive
      transfusion policy are given by patients' individual tolerance of acute
      normovolemic anemia. Artificial oxygen carriers based on perfluorocarbon or
      hemoglobin are attractive alternatives to allogenic red blood cells. There are
      many risks involved in allogenic blood transfusions and they include transmission
      of infections, delayed postoperative wound healing, transfusion reactions,
      immunomodulation and cancer recurrence. Regardless of whether artificial oxygen
      carriers are available for routine clinical use, further studies are needed in
      order to show the safety and efficacy of these substances for clinical practice.

PMID- 19597688
TI  - Suicide attempt using pure methanol with hospitalization of the patient soon
      after ingestion: case report.
AB  - CONTEXT: Most patients with methanol poisoning typically show up one to several
      days after ingestion, presenting severe acidosis, visual disorders, or both.
      Reports of hospitalization less than 6 h after exposure are unusual. We describe
      a case of attempted suicide using methanol admitted 3 h after ingestion. CASE
      REPORT: A 52-year-old male was hospitalized 3 h after intentional ingestion of
      150 ml of 99.9% methanol with no co-ingestion of ethanol. He was alert and
      cooperative, presenting nausea and vertigo, and reporting six episodes of
      vomiting. Physical examination showed no remarkable features. A blood sample for
      methanol and ethanol determination was obtained 4 h after ingestion. The result
      (available 10 h after ingestion) showed 70 mg/dl of methanol, without detectable
      ethanol. He was treated with a loading dose of 10% ethanol solution (7 ml/kg,
      intravenously), followed by a maintenance dose of 0.9-1.0 ml/kg/h intravenously
      (10 to 51 h); hemodialysis (19 to 27 h, together with 2.1 ml/kg/h of 10% ethanol
      intravenously); and folinic acid intravenously (50 mg every 6 h, from 4 to 51 h).
      He developed mild/moderate metabolic acidosis without acidemia and was discharged
      on day four after ophthalmological evaluation and cerebral computed tomography
      scan, without abnormalities. Follow-up revealed no sequelae. CONCLUSION: This
      could be classified as a potentially severe case of methanol poisoning, according
      to the amount and concentration of methanol ingested, and blood methanol
      concentration at 4 h. The good outcome was attributable to early hospitalization
      and early antidotal therapy with hemodialysis, starting at 10 and 19 h,
      respectively.

PMID- 19597687
TI  - Microinvasive carcinoma of the uterine cervix in a 14-year-old adolescent: case
      report and literature review.
AB  - CONTEXT: Cancer of the uterine cervix is rare during adolescence. The reported
      rates are 0/100,000 adolescents aged 10 to 19 years and 1.7/100,000 women aged 20
      to 24 years. However, several studies have shown increasing incidence of
      preneoplastic lesions at increasingly early ages. CASE REPORT: This paper reports
      a case of microinvasive carcinoma of the uterine cervix in a 14-year-old patient
      with menarche at 10 years of age and first coitus at 12 years of age. The
      objective of the present report was to alert gynecologists and pediatricians
      regarding the need for cervical carcinoma prevention among sexually active
      adolescents, based on educational programs that explain the purpose of
      colpocytological examinations and encourage their use, along with condom use and
      limitation of the number of sexual partners.

PMID- 19597690
TI  - A feasible lifestyle program for early intervention in patients with chronic
      obstructive pulmonary disease (COPD): a pilot study in primary care.
AB  - AIM: To evaluate the feasibility of a lifestyle program for early intervention in
      patients with COPD in a primary care population. METHODS: The study was performed
      in a Primary Health Care Centre in Western Sweden. During a four-week period, all
      smokers between 40-70 years of age were invited to answer a questionnaire and to
      perform spirometry. The intervention program included a specially designed
      smoking cessation program and programs for physical activity and diet. RESULTS:
      84 smokers were included. 42% fulfilled the criteria for COPD. All of the COPD
      patients were in GOLD stage I and II. Among the COPD subjects, 38% were
      underweight and 56% had a low fat-free mass - both together indicating
      malnutrition and the need for nutritional treatment. By the end of the
      intervention program, 47% of the COPD patients had stopped smoking. CONCLUSIONS:
      The intervention program was feasible and effective with a very high smoking
      cessation rate.

PMID- 19597691
TI  - Re: Pain and depression influence outcome 5 years after knee replacement surgery.

PMID- 19597692
TI  - Effects of dopaminergic medication on objective tasks of deftness,  bradykinesia
      and force control.
AB  - At least one small report has suggested the possibility that limb kinetic apraxia
      (a deficit in deftness) was not dopamine responsive and independent of
      bradykinesia and rigidity in PD. Quencer et al. (Neurology 68:150-151, 2007)
      observed that speed of finger tapping (bradykinesia) in optimally medicated
      persons with PD was largely comparable to healthy controls, yet their ability to
      manipulate and rotate a coin (deftness) was impaired. The authors concluded that
      deftness was independent of parkinsonian features. In this study, we measured
      tasks of deftness in a more objective way in both the ON and OFF dopaminergic
      state. Further, we evaluated whether finger-thumb force control was compromised
      in persons with PD. Eleven PD fluctuators (mean age 68 +/- 9 years) and ten
      healthy age-matched controls (68 +/- 8 years) were included. The bradykinesia
      items in the UPDRS and performance on the large box and block (LBB) tests were
      used to measure bradykinesia. A small box and block test (SBB), small coin
      rotation task (SCR) and small lock rotation task (SLR) were used as measures of
      deftness. Statistical analyses revealed a significant improvement in performance
      for the LBB, SBB, SLR and the bradykinesia items of the UPDRS following
      medication. Furthermore, our PD cohort's scores were comparable to controls on
      tests of bradykinesia and deftness (SLR, SBB and LBB) in the ON state, but they
      performed statistically worse than controls in the OFF state. On the other hand,
      analyses of the force control tasks revealed no significant difference between
      the groups. In summary, the improvement in deftness and bradykinesia in the ON
      state among our PD cohorts (and their comparable performance in the ON but not
      OFF state compared to healthy controls) suggests the possibility of a more
      uniform response of these motor features to dopaminergic therapy in PD.

PMID- 19597693
TI  - Tremor in Klinefelter's syndrome improved by testosterone administration.
AB  - Tremor in Klinefelter's syndrome is believed to be essential tremor since the
      publication of "Klinefelter's syndrome and essential tremor" in 1969. However,
      the author also stated that tremor in Klinefelter's syndrome might differ from
      essential tremor. A 71-year-old man with Klinefelter's syndrome who suffers from
      postural hand tremor is described. The electromyogram indicated lower motor
      neuron disturbance and chronic neurogenic change. The muscle biopsy indicated
      neurogenic muscle atrophy. Upon testosterone administration, the amplitude of
      tremor was reduced and a gradual improvement in handwriting was observed. The
      tremor in this patient was different from essential tremor. The foresight by
      Baughman in 1969 proved to be true in this patient. This case report provides new
      insights into the pathogenesis and treatment of tremor in Klinefelter's syndrome,
      which would benefit patients who suffer from the tremor.

PMID- 19597694
TI  - Melandrium yellow fleck bromovirus infects Arabidopsis thaliana and has genomic
      RNA sequence characteristics that are unique among bromoviruses.
AB  - Melandrium yellow fleck bromovirus (MYFV) systemically infected Arabidopsis
      thaliana, although the susceptibility of several A. thaliana accessions to MYFV
      differed from their susceptibility to the other two bromoviruses infecting A.
      thaliana. We constructed full-length cDNA clones of MYFV genomic RNAs 1, 2, and 3
      and determined their complete nucleotide sequences. Similar to Broad bean mottle
      bromovirus, (1) the 5'-terminal nucleotide of the MYFV genomic RNAs was adenine,
      and (2) the "D-arm" was absent from the tRNA-like structure in the 3'
      untranslated regions (UTRs) of MYFV RNAs. As unique characteristics, MYFV RNA3
      lacked the poly(A) tract in the intercistronic region and contained a directly
      repeated sequence of about 200 nucleotides and polypyrimidine tracts of
      heterogeneous lengths in the 5' UTR. Co-infection experiments using RNA3 clones
      with or without the duplicated sequence demonstrated that the duplication
      contributed to the competitive fitness of the virus in Nicotiana benthamiana.

PMID- 19597695
TI  - Molecular characterization and detection of recombinant isolates of potato virus
      Y from China.
AB  - Although potato virus Y (PVY) is one of the most economically important pathogens
      of potatoes in China, few studies have been carried out to characterize the virus
      in that country. Using reverse transcription-polymerase chain reaction (RT-PCR)
      based genotyping developed previously, two types of recombinant PVY were
      identified in China for the first time. One resembled the European (Eu) type of
      potato tuber necrosis strain (Eu-PVY(NTN)), possessing three widely recognized
      recombinant joints (RJs 1-3) of the common strain (PVY(O)) and the Eu- type
      tobacco veinal necrosis strain (Eu-PVY(N)). The other, on the other hand,
      appeared to have only RJ1 and RJ2. The complete genome of a representative
      isolate, PVY-HN2, from the second type was subsequently sequenced. Comparison of
      the sequence of 'HN2' with those of PVY(O) and Eu-PVY(N) not only confirmed the
      recombinant nature of 'HN2' but also revealed the existence of three recombinant
      events in the isolate, similar to that in PVY(NTN)-Hun. However, the two isolates
      differed significantly at RJ1 (PVY(NTN)-Hun vs. HN2, nt 2419 vs. nt 2521) and RJ3
      (PVY(NTN)-Hun vs. HN2, nt 9183 vs. nt 8572) and slightly at RJ2 (PVY(NTN)-Hun vs.
      HN2, nt 5844 vs. nt 5867). A primer pair was developed to facilitate the
      detection of the alternative RJ3. Using the newly and previously designed RJ
      primers, all targeted RJs were detected. Interestingly, tests of the available
      PVY samples indicated that two were doubly infected with both types of
      recombinant PVY, further confirming the effectiveness of the detection. Further
      analysis of these samples using enzyme-linked immunosorbent assay and bioassay
      revealed that 'HN2' possesses a PVY(O) serotype, a PVY(N) pathotype in tobacco
      and a PVY(NTN) pathotype in potato.

PMID- 19597696
TI  - Molecular diversity and catalytic activity of Thermus DNA polymerases.
AB  - Thermus aquaticus DNA polymerase (Taq polymerase) made the polymerase chain
      reaction feasible and led to a paradigm shift in genomic analysis. Other Thermus
      polymerases were reported to have comparable performance in PCR and there was an
      analysis of their properties in the 1990s. We re-evaluated our earlier phylogeny
      of Thermus species on the basis of 16S rDNA sequences and concluded that the
      genus could be divided into eight clades. We examined 22 representative isolates
      and isolated their DNA polymerase I genes. The eight most diverse polymerase
      genes were selected to represent the eight clades and cloned into an expression
      vector coding for a His-tag. Six of the eight polymerases were expressed so that
      there was sufficient protein for purification. The proteins were purified to
      homogeneity and examination of the biochemical characteristics showed that
      although they were competent to perform PCR, none was as thermostable as
      commercially available Taq polymerase; all had similar error-frequencies to Taq
      polymerase and all showed the expected 5'-3' exonuclease activity. We conclude
      that the initial selection of T. aquaticus for DNA polymerase purification was a
      far-reaching and fortuitous choice but simple mutagenesis procedures on other
      Thermus-derived polymerases should provide comparable thermostability for the PCR
      reaction.

PMID- 19597698
TI  - IgG subclass serum levels in systemic lupus erythematosus patients.
AB  - IgG subclass levels of sera from 105 patients with systemic lupus erythematosus
      (SLE) were determined by immunonephelometric assay. Patients were divided into
      two groups according to clinical activity of the disease: active disease and
      remission. Forty-five normal controls were also measured. We found a significant
      increase of IgG1 (p = 0.000), IgG2 (p = 0.000), and IgG3 (p = 0.000) in SLE sera,
      while IgG4 (p = 0.494) values did not differ significantly from those of
      controls. When patients were divided according to clinical activity, decrease of
      IgG3 concentration was observed in the patients in remission. In contrast, the
      concentrations of IgG1, IgG2, and IgG4 subclass were similar between the two
      groups (p > 0.05). Our data suggest that differential increase of IgG subclasses
      during the course of SLE may be of relevance to the pathogenesis of the disease.

PMID- 19597697
TI  - Microbial activity and diversity during extreme freeze-thaw cycles in periglacial
      soils, 5400 m elevation, Cordillera Vilcanota, Peru.
AB  - High-elevation periglacial soils are among the most extreme soil systems on Earth
      and may be good analogs for the polar regions of Mars where oligotrophic mineral
      soils abut with polar ice caps. Here we report on preliminary studies carried out
      during an expedition to an area where recent glacial retreat has exposed porous
      mineral soils to extreme, daily freeze-thaw cycles and high UV fluxes. We used in
      situ methods to show that inorganic nitrogen (NO(3) (-) and NH(4) (+)) was being
      actively cycled even during a period when diurnal soil temperatures (5 cm depth)
      ranged from -12 to 27 degrees C and when sub-zero, soil cooling rates reached 1.8
      degrees C h(-1) (the most rapid soil cooling rates recorded to date).
      Furthermore, phylogenetic analyses of microbial phylotypes present at our highest
      sites (5410 m above sea level) showed the presence of nitrifying bacteria of the
      genus Nitrospira and newly discovered nitrite-oxidizing Betaproteobacteria. These
      soils were overwhelmingly dominated (>70% of phylotypes) by photosynthetic
      bacteria that were related to novel cyanobacteria previously found almost
      exclusively in other plant-free, high-elevation soils. We also demonstrated that
      soils from our highest sites had higher potential for mineralizing glutamate and
      higher microbial biomass than lower elevation soils that had been more recently
      covered by ice. Overall, our findings indicate that a diverse and robustly
      functioning microbial ecosystem is present in these previously unstudied high
      elevation soils.

PMID- 19597699
TI  - Autoantibodies and other serological markers in rheumatoid arthritis: predictors
      of disease activity?
AB  - The description of potential serological markers of rheumatoid arthritis (RA)
      activity can be quite useful in optimizing RA treatment, since the laboratory
      markers currently used, namely erythrocyte sedimentation rate and C-reactive
      protein, are not specific for RA and are influenced by several other variables.
      The markers proposed for assessing RA activity include rheumatoid factor, anti
      citrullinated protein/peptide antibodies, immunoglobulin M (IgM) anti-IgG
      advanced glycation end products, markers of bone/cartilage metabolism, mannose
      binding lectin, E-selectin, interleukin-6, and leptin. Various studies have
      investigated the correlation between some of these markers and other variables
      that might indicate disease activity, e.g., inflammatory activity tests and
      disease activity scores. However, there is as yet insufficient evidence that any
      of these markers, in isolation or in combination, are useful in the assessment of
      RA activity.

PMID- 19597701
TI  - Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial
      tumor gene expression.
AB  - Oligodendroglial tumors presenting loss of heterozygosity (LOH) at 1p and 19q
      have been shown to be sensitive to chemotherapy, thus making 1p-19q status
      testing a key aspect in oligodendroglioma diagnosis and prognosis. Twenty-nine
      tumor samples (19 oligodendrogliomas, 10 oligoastrocytomas) were analyzed in
      order to obtain a molecular profile identifying those bearing 1p-19q LOH. Other
      genomic anomalies usually present in gliomas, such as EGFR amplification,
      CDKN2A/ARF deletion, 10q LOH and TP53 mutation, were also studied. Tumors with 1p
      19q LOH overexpressed genes related to neurogenesis. Genes linked to immune
      response, proliferation and inflammation were overexpressed in the group with
      intact 1p-19q; this group could in turn be further divided in two subgroups: one
      overexpressing genes involved in immune response and inflammation that did not
      show major genetic aberrations other than the TP53 mutation and EGFR trisomy in a
      few cases, and another overexpressing genes related to immune response and
      proliferation that had a predominance of samples carrying several anomalies and
      presenting worse outcomes. This molecular signature was validated by analyzing a
      set of ten tumor samples (three oligodendrogliomas, seven oligoastrocytomas); all
      ten samples were correctly assigned. LOH at 1p-19q results in haploinsufficiency
      and copy number reduction of several genes, including NOTCH 2; this phenomenon
      produces a global change in gene expression inducing a pro-neural status that
      results in restrictions to cell migration and proliferation. Tumors without LOH
      at 1p-19q exhibit the opposite characteristics, explaining their more aggressive
      behavior.

PMID- 19597700
TI  - Diversity in arrestin function.
AB  - The termination of heptahelical receptor signaling is a multilevel process
      coordinated, in large part, by members of the arrestin family of proteins.
      Arrestin binding to agonist-occupied receptors promotes desensitization by
      interrupting receptor-G protein coupling, while simultaneously recruiting
      machinery for receptor endocytosis, vesicular trafficking, and receptor fate
      determination. By simultaneously binding other proteins, arrestins also act as
      ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase,
      phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein
      'signalsome' complexes. Arrestin-binding thus 'switches' receptors from a
      transient G protein-coupled state to a persistent arrestin-coupled state that
      continues to signal as the receptor transits intracellular compartments. While it
      is clear that signalsome assembly has profound effects on the duration and
      spatial characteristics of heptahelical receptor signals, the physiologic
      functions of this novel signaling mechanism are poorly understood. Growing
      evidence suggests that signalsomes regulate such diverse processes as endocytosis
      and exocytosis, cell migration, survival, and contractility.

PMID- 19597702
TI  - Low level alcohol intake, cigarette smoking and risk of breast cancer in Asian
      American women.
AB  - Studies have shown that breast cancer incidence rates among Asian migrants to the
      United States approach US incidence rates over several generations, implicating
      potentially modifiable exposures such as moderate alcohol use that has been
      linked to excess breast cancer risk in other populations. The goal of this study
      was to investigate the effect of alcohol intake, primarily low levels, on breast
      cancer risk in Asian-American women and explore whether smoking and alcohol
      contributed to the breast cancer incidence rates observed among Asian migrants to
      the United States. Study subjects in this population-based case-control study
      included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino
      ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966
      population controls frequency matched on age, ethnicity, and area of residence.
      The fraction of smokers and drinkers was significantly higher in women born in
      Western compared with Eastern countries. However, breast cancer risk was not
      significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence
      interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in
      this population of low consumers of alcohol (median intake among drinkers in
      grams per day was 0.48 for cases and 0.40 for controls). These data suggest that
      low alcohol intake is not related to increased breast cancer risk in Asian
      American women and that neither alcohol nor cigarette use contributed to the
      elevated risks in Asian-American women associated with migration patterns and
      Westernization.

PMID- 19597704
TI  - Correlation of HER2 status between primary tumors and corresponding circulating
      tumor cells in advanced breast cancer patients.
AB  - Biocharacterization of circulating tumor cells (CTCs) in the peripheral blood of
      advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We
      assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were
      separated and stained using the CellSearch System((R)). HER2 status was assessed
      by immunofluorescence and, when technically feasible, by fluorescence in situ
      hybridization. Blood samples were obtained from 66 ABC patients. Forty patients
      had a positive CTC sample (61%) and of these, 15 (37%) had HER2 + CTCs. We found
      non-concordant results in 32% of cases: 29% (8/28) of HER2-negative primary
      tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had
      HER2-negative CTCs (k = 0.278). Our study suggests that a subset of patients with
      HER2-negative primary tumors develops HER2-positive CTCs during disease
      progression.

PMID- 19597703
TI  - Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4:
      response and biomarkers in tamoxifen users.
AB  - Retrospective studies suggest that single nucleotide polymorphisms in the
      cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better
      tolerance and worse treatment outcome. We hypothesized that women with this
      genotype lack tamoxifen-induced endometrial and biochemical changes in follicle
      stimulating hormone (FSH) and sex hormone-binding globulin (SHBG). We identified
      56 breast cancer patients attending the follow-up clinic with a homozygous mutant
      (HM) status for the CYP2D6*4 null variant. Here, we report a detailed assessment
      of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen
      either for metastatic (n = 5) or for early disease (n = 14). We assessed response
      to tamoxifen in metastatic disease. Endometrial appearances and serum levels of
      FSH and SHBG were assessed from retrospective and prospective testing. Our
      findings do suggest that the presence of two CYP2D6*4 alleles does not exclude a
      durable response of tamoxifen in metastatic breast cancer. The transvaginal
      ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on
      tamoxifen is similar as seen in the normal population of tamoxifen users. The
      endometrium is increased in thickness with subepithelial cysts and endometrial
      polyps. Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the
      range of what would be expected during tamoxifen treatment in the general
      population. Our findings do show CYP2D6*4/*4 carriers to have activity of
      tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. They
      support clinical trials prospectively testing the effect of CYP2D6 genetic
      variability in response to tamoxifen before denying this drug to breast cancer
      patients only based on their CYP2D6*4 status.

PMID- 19597705
TI  - Adult human mesenchymal stem cells enhance breast tumorigenesis and promote
      hormone independence.
AB  - Adult human mesenchymal stem cells (hMSCs) have been shown to home to sites of
      breast cancer and integrate into the tumor stroma. We demonstrate here the effect
      of hMSCs on primary breast tumor growth and the progression of these tumors to
      hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary
      tumor growth of the estrogen receptor-positive, hormone-dependent breast
      carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige
      mice. We also show hormone-independent growth of MCF-7 cells when co-injected
      with hMSCs. These effects were found in conjunction with increased
      immunohistochemical staining of the progesterone receptor in the MCF-7/hMSC
      tumors as compared to MCF-7 control tumors. This increase in PgR expression
      indicates a link between MCF-7 cells and MSCs through ER-mediated signaling.
      Taken together, our data reveal the relationship between tumor microenvironment
      and tumor growth and the progression to hormone independence. This tumor stroma
      cell interaction may provide a novel target for the treatment of estrogen
      receptor-positive, hormone-independent, and endocrine-resistant breast carcinoma.

PMID- 19597706
TI  - Vanadium pentoxide effects on stress responses in wine Saccharomyces cerevisiae
      strain UE-ME3.
AB  - Vanadium pentoxide mainly used as catalyst in sulphuric acid, maleic anhydride
      and ceramics industry, is a pollutant watering redistributed around the
      environment. Research on biological influence of vanadium pentoxide has gained
      major importance because it exerts toxic effects on a wide variety of biological
      systems. In this work we intent to evaluate the effects of vanadium pentoxide
      ranging from 0 to 2 mM in culture media on a wine wild-type Saccharomyces
      cerevisiae from Alentejo region of Portugal. Our results show that 2.0 mM
      vanadium pentoxide in culture medium induced a significant increase of
      malonaldehyde level and Glutathione peroxidase activity, a slightly increase of
      Catalase A activity as well as a decrease of wet weight and mitochondrial NADH
      cit c reductase of S. cerevisiae UE-ME(3). Also our results show that
      cycloheximide prevent cell death when cells grows 30 min in presence of 1.5 mM of
      vanadium pentoxide.

PMID- 19597707
TI  - Ecotoxicological evaluation for the screening of areas polluted by mining
      activities.
AB  - The aim of this study was to evaluate the applicability of three bioassays
      representing multiple trophic levels, for the preliminary ecotoxicological
      screening of sediments from sites contaminated by mining activities. Of the
      bioassays used in this study, the ostracod test was the most responsive. Vibrio
      fischeri luminescence inhibition assay was less sensitive to the toxicants in the
      sediments than the phytotoxicity assays. The general trend observed was an
      increase in toxicity values measured by the bioassays with increasing metal
      mobilization in sediment samples. Therefore, the test battery can be used as a
      rapid and sensitive tool to evaluate the heavy metal contamination in sediments.

PMID- 19597708
TI  - Cyclooxygenase-2 immunoreactivity and protein level in the gerbil hippocampus
      during normal aging.
AB  - Cyclooxygenases-2 (COX-2) is not only related to inflammation but also plays
      critical roles in brain development and synaptic signaling. In the present study,
      we investigated age-related changes in COX-2 immunoreactivity and protein levels
      in the gerbil hippocampus. In the hippocampal CA1 region (CA1) and dentate gyrus
      (DG), weak COX-2 immunoreactivity was observed at postnatal month 1 (PM 1), and
      COX-2 immunoreactivity was markedly increased at PM 18 and 24. In the CA2/3, COX
      2 immunoreactivity was strong at PM 1. COX-2 immunoreactivities in the PM 3, 6
      and 12 groups were decreased compared to that in the PM 1 group, and it was
      increased at PM 18 and 24. In addition, age-related changes in COX-2 levels were
      similar with immunohistochemical results in the CA2/3. These results suggest that
      COX-2 immunoreactivity and levels were high in the hippocampus of aged gerbils.

PMID- 19597710
TI  - Hydroxamate siderophores of Scedosporium apiospermum.
AB  - Scedosporium apiospermum is an emerging pathogen colonizing the airways of
      patients with cystic fibrosis and causing severe infections in immunocompromised
      hosts. In order to improve our knowledge on the pathogenic mechanisms of this
      fungus, we investigated the production of siderophores. Cultivation on CAS medium
      and specific assays for different classes of siderophores suggested the secretion
      of hydroxamates. A maximal production was obtained by cultivation of the fungus
      at alkaline pH in an iron-restricted liquid culture medium. Siderophores were
      then extracted from the culture filtrate by liquid/liquid extraction, and
      separated by reverse phase high performance liquid chromatography. Two
      siderophores, dimerumic acid and Nalpha-methyl coprogen B, were identified by
      electrospray ionization-mass spectrometry and MS-MS fragmentation. Finally,
      comparison of various strains suggested a higher production of Na-methyl coprogen
      B by clinical isolates of respiratory origin. Studies are initiated in order to
      determine the potential usefulness of these siderophores as diagnostic markers of
      scedosporiosis.

PMID- 19597709
TI  - Mechanism of post-translational modification by tyrosine phosphorylation of
      apoptotic proteins during hypoxia in the cerebral cortex of newborn piglets.
AB  - The present study aims to investigate the mechanism of phosphorylation of
      apoptotic proteins and tests the hypothesis that the hypoxia-induced increased
      tyrosine phosphorylation of apoptotic proteins Bcl-2 and Bcl-xl is Ca(2+)-influx
      dependent. Piglets were divided in normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and
      hypoxic-pretreated with clonidine (Clo + Hx, n = 4) groups. Hypoxic animals were
      exposed to an FiO(2) of 0.06 for 1 h. Clonidine (12.5 microg/kg, IV) was
      administered to piglets 30 min prior to hypoxia. Hypoxia was confirmed by ATP and
      phosphocreatinine (PCr) levels. Cytosol was isolated and separated by 12% SDS
      PAGE and probed with tyrosine phosphorylated (p) -Bax, Bad, Bcl-2 and Bcl-xl
      antibodies and bands were detected. The ATP levels (micromol/g brain) in the Nx,
      Hx, Clo + Hx were 4.3 +/- 1.0 (P < 0.05 vs. Hx, Clo-Hx), 0.9 +/- 0.8 and 1.5 +/-
      0.3, respectively. The PCr levels in the Nx, Hx, Clo + Hx were 2.7 +/- 0.7 (P <
      0.05 vs. Hx, Clo-Hx), 0.9 +/- 0.2 and 0.9 +/- 0.9, respectively. Ca(2+)-influx
      (pmoles/mg protein) was 4.96 +/- 0.94 in Nx, 11.11 +/- 2.38 in Hx, and 6.23 +/-
      2.07 in Clo + Hx (P < 0.05 Nx vs. Hx and Hx vs. Clo + Hx). p-Bcl-2 density was
      21.1 +/- 1.1 Nx, 58.9 +/- 9.6 Hx and 29.5 +/- 6.4 Clo + Hx (P < 0.05 vs. Hx). p
      Bcl-xl density was 29.6 +/- 1.5 Nx, 50.6 +/- 7.4 Hx and 32.1 +/- 0.1 Clo + Hx (P
      < 0.05 vs. Hx). p-Bax density was 38.6 +/- 16.2 Nx, 46.1 +/- 5.5 Hx and 41.6 +/-
      1.9 Clo + Hx groups (P = NS). p-Bad was 66.7 +/- 12.8 Nx, 71.2 +/- 6.8 Hx and
      78.7 +/- 22.5 Clo + Hx groups (P = NS). Results showed that clonidine
      administration prior to hypoxia prevents the hypoxia-induced increased nuclear
      Ca(2+)-influx and increased phosphorylation of Bcl-2 and Bcl-xl while
      phosphorylation of Bad and Bax was not altered. We conclude that post
      translational modification of anti-apoptotic proteins Bcl-2 and Bcl-xl during
      hypoxia is nuclear Ca(2+)-influx-dependent. We propose that blockade of nuclear
      Ca(2+)-influx that prevents phosphorylation of antiapoptotic proteins may become
      a neuroprotective strategy.

PMID- 19597712
TI  - Assessment of heavy metal pollution in river water of Hanoi, Vietnam using
      multivariate analyses.
AB  - Concentrations of heavy metals in water of the Nhue River (a suburban/rural
      river) and one of its tributaries, the To Lich River (an urban river), in Hanoi,
      Vietnam had been monitored, and spatial and seasonal variations in their
      composition were evaluated by means of principal component analysis and cluster
      analysis. Heavy metal concentrations in water of the two rivers were generally
      lower than the surface water quality standard in Vietnam, except for manganese in
      several sites, although they were higher than the median values in freshwater of
      the world by 0.42-43 times in Nhue and 0.13-32 times in To Lich. The two
      multivariate analyses represented that the composition of heavy metals in river
      water of To Lich was distinctly different from that of Nhue. It was also
      suggested that metal concentrations and their composition in Nhue river water
      would be affected by inflowing water of To Lich and wastewater discharged from
      the up- and middle-stream basin, and that they gradually recovered along the
      direction of water flow in the downstream area in rainy season.

PMID- 19597711
TI  - The association between vitamin D status and circulating adiponectin independent
      of adiposity in subjects with abnormal glucose tolerance.
AB  - Vitamin D status assessed by serum 25-hydroxyvitamin D levels (25(OH)D) has been
      shown to be inversely associated with insulin resistance. The underlying basis
      for such association is less clear. In the present study, we assessed the
      prevalence of inadequate vitamin D levels and its relationship to glucose
      tolerance status and circulating adiponectin in healthy Thai population. The
      cohort of 246 subjects was classified into two groups according to 75 g oral
      glucose tolerance test (OGTT) results. There were 86 subjects and 160 subjects in
      normal glucose tolerance group (NGT) and abnormal glucose tolerance group (AGT),
      respectively. Anthropometric variables were recorded for each individual. Fasting
      blood samples were assayed for 25(OH)D, adiponectin, glucose, and insulin levels.
      Insulin resistance (HOMA-IR) and insulin secretion index (HOMA-B) were calculated
      by the homeostasis model assessment. Pearson and partial correlation analyses
      were performed. There were 35 males and 211 females with a mean age of 62.4 +/-
      7.2 years in this study. The mean levels of 25(OH)D were 21.4 +/- 6.6 ng/ml. The
      prevalence of vitamin D deficiency defined by 25(OH)D levels less than 20 ng/ml
      and vitamin D inadequacy defined by 25(OH)D levels less than 30 ng/ml were 44.3
      and 91.9%, respectively. The mean levels of 25(OH)D obtained from samples
      collected in the rainy season (19.4 +/- 4.6 ng/ml) were significantly lower than
      those collected in the winter (22.6 +/- 8.3 ng/ml) and summer period (23.1 +/-
      4.6 ng/ml). AGT subjects had slightly lower average 25(OH)D levels than the NGT
      group (21.0 +/- 6.8 vs. 22.1 +/- 6.2 ng/ml, P = 0.09). 25(OH)D levels were
      positively associated with adiponectin levels (r = 0.20, P < 0.05) and negatively
      associated with HOMA-IR and BMI (r = -0.22, P < 0.01 and r = -0.22, P < 0.01,
      respectively) only in AGT subjects. An independent association between 25(OH)D
      and adiponectin levels was demonstrated after controlling for BMI (r = 0.17, P <
      0.05). High prevalence of vitamin D inadequacy and seasonal variation of vitamin
      D status are found in Thai population. We demonstrated an association between
      insufficient vitamin D status and lower circulating adiponectin in subjects with
      abnormal glucose tolerance independently of adiposity which may indicate the role
      of adiponectin as a link between vitamin D status and insulin resistance.

PMID- 19597713
TI  - Content of lead and cadmium in barred hogfish, Bodianus scrofa, island grouper,
      Mycteroperca fusca, and Portuguese dogfish, Centroscymnus coelolepis, from Canary
      Islands, Spain.
AB  - Concentration of lead and cadmium has been analyzed in Bodianus scrofa and
      Mycteroperca fusca captured in the Canary Islands coast. Concentration of Pb
      ranged from 2.53 to 306.40 and 4.97 to 792.00 microg kg(-1) respectively, while
      that of Cd ranged from 1.75 to 1854.50 and 6.78 to 656.00 microg kg(-1). The same
      metals have been analyzed in muscles, liver and skin of Centroscymnus coelolepis
      from Canary Islands, with contents of Pb and Cd ranged between 24.18-96.12 microg
      kg(-1) and 32.00-3266.58 microg kg(-1) respectively, and in the Azores
      Archipelago, with concentrations of Pb and Cd ranged as follow: 18.41-38.99
      microg kg(-1) and 5.23-4179.87 microg kg(-1) respectively. Percentage of
      contribution of both metals to the PTWIs, has also been calculated for both
      fishes.

PMID- 19597714
TI  - Outside-in transobturator midurethral sling and the dorsal nerve of the clitoris.
AB  - INTRODUCTION AND HYPOTHESIS: An anatomical study on fresh cadavers was done to
      determine the vulnerability of the dorsal nerve of the clitoris to injury during
      "outside-in" transobturator sling procedures. METHODS: The dorsal nerve of the
      clitoris was identified bilaterally in ten fresh cadavers. Transfixing needles
      marked the inferomedial border of the obturator foramen. The distance between the
      foramen border and the nerve was measured. RESULTS: The nerve ran medially in
      close approximation to the ischiopubic ramus and inferior to the obturator
      foramen in all specimens. In no instance did the nerve follow an aberrant course
      traversing the obturator foramen. The mean distance between the inferomedial
      border of the obturator foramen and the nerve was 9.3 mm, range 3-14 mm.
      CONCLUSIONS: When the "outside-in" technique is used, the introducer cannot come
      into contact with the dorsal nerve of the clitoris because the introducer would
      have to pass through the ischio-pubic ramus. This is not anatomically possible.

PMID- 19597715
TI  - Incontinence and detrusor dysfunction associated with pelvic organ prolapse:
      clinical value of preoperative urodynamic evaluation.
AB  - INTRODUCTION AND HYPOTHESIS: We examined how preoperative urodynamic findings are
      related to the urinary problems following surgical repair of pelvic organ
      prolapse (POP). METHODS: The clinical records of 87 women who underwent surgery
      for POP were reviewed retrospectively. Preoperatively, cough stress test and
      urodynamic testing, including pressure-flow study, were performed with prolapse
      reduction. Postoperative evaluation included uroflowmetry, postvoid residuals,
      and symptom assessment using questionnaires. RESULTS: A cough stress test with
      simple filling was sufficient for diagnosis of occult stress urinary incontinence
      (SUI). The presence of detrusor overactivity was a good predictor of
      postoperative persistence of urgency and urge urinary incontinence. Postvoid
      residuals (PVR) largely increased immediately after surgery, but usually
      recovered within 1 month. Poor detrusor contractility was the best predictor of
      large PVR occurrence. CONCLUSIONS: Preoperative urodynamic evaluation of SUI and
      detrusor function was useful for predicting postoperative urinary conditions in
      POP patients. Its cost-effectiveness remains to be examined.

PMID- 19597716
TI  - Blind hemibladder, ectopic ureterocele, or Gartner's duct cyst in a woman with
      Mullerian malformation and supposed unilateral renal agenesis: a case report.
AB  - Genital anomalies associated with unilateral renal agenesis are generally due to
      agenesis or hypoplasia of the entire urogenital ridge or distal mesonephric
      aberrations. However, renal adysplasia could also occur in association with
      anomalies of the ventral urogenital sinus. The patient presented didelphys uterus
      in the superior uterine segment, a septate cervix, and a simple vagina. After
      transvaginal puncture and injection of a contrast agent into the bulge observed
      in the right vaginal wall, a filled sac or cavity was detected, possibly a
      hemibladder. This structure continued upward with a possible dilated tortuous
      ureter that filled retrogradely. Magnetic resonance imaging also showed the
      presence of the right blind paravaginal sac. Right hemitrigone and ureteral
      orifice were absent in the cystourethroscopy. No right kidney was found, despite
      the use of multiple imaging techniques. Blind hemibladder, ectopic ureterocele,
      and Gartner's duct cyst seem to be a possible diagnosis associated to Mullerian
      malformations and supposed unilateral renal agenesis. Therefore, Mullerian
      anomalies without combined mesonephric alteration could be associated with
      conditions of the ventral urogenital sinus, including blind hemibladder or
      ectopic ureterocele with secondary renal dysplasia.

PMID- 19597717
TI  - Tension-free vaginal tape bowel perforation.
AB  - A 73-year-old para 3 white female with posthysterectomy pelvic organ prolapse and
      stress urinary incontinence underwent pelvic reconstructive surgery and placement
      of tension-free vaginal tape. On postoperative day 4, she underwent exploratory
      laparotomy for small bowel obstruction. She was found to have an injury to the
      small bowel secondary to a through-and-through perforation by tension-free
      vaginal tape. The entire tape was removed. Partial small bowel resection and
      primary anastomosis were performed. Her subsequent recovery was uneventful.

PMID- 19597718
TI  - TVT-O versus Monarc after a 2-4-year follow-up: a prospective comparative study.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare outcome and
      quality of life of tension-free vaginal tape "inside-out" (TVT-O) and Monarc
      transobturator tapes after 2-4 years. METHODS: The method used was a prospective
      comparative study. Participants (n = 191) were assigned to either a TVT-O (n =
      93) or a Monarc (n = 98) procedure. Cure of stress urinary incontinence (SUI) was
      defined as the statement of the woman of not experiencing any loss of urine upon
      physical exercise. RESULTS: Cure rates after 2-4 years were 72% for TVT-O and 65%
      for Monarc, while improvement was observed in, respectively, 12% and 21% (p =
      0.3). There was a statistically significant improvement in quality of life but no
      differences were found between both procedures. CONCLUSIONS: After a 2-4-year
      follow-up period, both procedures were equally safe and effective in curing SUI.

PMID- 19597719
TI  - Symptoms of pelvic floor dysfunction are poorly correlated with findings on
      clinical examination and dynamic MR imaging of the pelvic floor.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to determine whether
      patients' symptoms agree with findings on clinical examination and dynamic MR
      imaging of the pelvic floor. METHODS: Symptoms of pelvic organ dysfunction were
      measured with the use of three validated questionnaires. The domain scores were
      compared with POP-Q and dynamic MR imaging measurements. The Spearman's rank
      correlation coefficient (r(s)) was used to assess agreement. RESULTS: Only the
      domain score genital prolapse was significantly correlated in the positive
      direction with the degree of pelvic organ prolapse as assessed by POP-Q and
      dynamic MR imaging (r(s) = 0.64 and 0.27, respectively), whereas the domain score
      urinary incontinence was inversely correlated (r(s) = -0.32 and -0.35,
      respectively). CONCLUSIONS: The sensation or visualization of a bulge in the
      vagina was the only symptom which correlated positively with the degree of pelvic
      organ prolapse, and clinical examination and dynamic MR imaging showed similar
      correlation in this respect.

PMID- 19597720
TI  - Effect of zinc supplementation on antioxidant activity in young wrestlers.
AB  - This study aims to examine the effect of zinc supplementation on free-radical
      formation and antioxidant system in individuals who are actively engaged in
      wrestling as a sport. The study registered a total of 40 male subjects, of whom
      20 were wrestlers and 20 were sedentary individuals. The subjects were equally
      allocated to four groups: group 1, zinc-supplemented sportsmen group; group 2,
      sportsmen group without supplementation; group 3, zinc-supplemented sedentary
      group; group 4, sedentary group without supplementation. Blood samples were
      collected from all subjects twice, once at the beginning of the study and once
      again at the end of 8-week procedures. The blood samples collected were analyzed
      to determine the levels of malondialdehyde (MDA), serum glutathione (GSH), serum
      glutathione peroxidase (GPx) activity, serum superoxide dismutase (SOD) activity
      (ELISA colorimetric method) and zinc (colorimetric method). No difference was
      found between MDA levels of the study groups in the beginning of the study. The
      highest MDA value at the end of the study was obtained in group 4 (p < 0.01). MDA
      levels in group 2 were established to be significantly higher than those in
      groups 1 and 3 (p < 0.01). GSH level, GPx, and SOD activities and zinc level
      measured in the beginning of the study were not different between groups.
      Measurements performed at the end of the study showed that groups 1 and 3 (zinc
      supplemented groups) had the highest GSH level, GPx, and SOD activities and zinc
      level (p < 0.01). These parameters were not different in the groups without
      supplementation (groups 2 and 4). Results obtained at the end of the study
      indicate that zinc supplementation prevents production of free radicals by
      activating the antioxidant system. In conclusion, physiologic doses of zinc
      supplementation to athletes may beneficially contribute to their health and
      performance.

PMID- 19597721
TI  - Distribution and speciation of arsenic by transplacental and early life exposure
      to inorganic arsenic in offspring rats.
AB  - The amount of arsenic compounds was determined in the liver and brain of pups and
      in breast milk in the pup's stomach in relation to the route of exposure:
      transplacental, breast milk, or drinking water. Forty-eight pregnant rats were
      randomly divided into four groups, each group was given free access to drinking
      water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6)
      until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the
      same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs),
      monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic
      acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast
      milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride
      generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and
      DMA in the breast milk, the brain, and the liver of the pups increased with the
      concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to
      the liver or brain, breast milk had the lowest arsenic concentrations. There was
      a significant decrease in the levels of arsenic species on PND 15 compared to PND
      0, 28, or 42. It was confirmed that arsenic species can pass through the
      placental barrier from dams to offspring and across the blood-brain barrier in
      the pups, and breast milk from dams exposed to arsenic in drinking water contains
      less arsenic than the liver and brain of pups.

PMID- 19597722
TI  - Selenoenzymes, laboratory parameters, and trace elements in different types of
      thyroid tumor.
AB  - This study was performed to investigate selenoenzyme activities and trace element
      concentrations in thyroid tissues, with reference to other parameters routinely
      used to characterize thyroid function. This was to reveal relevant parameters as
      possible additional markers of tumor grade, clinical course, and prognosis of
      thyroid disorders. The tissue samples were obtained during surgical treatment
      (total or near total thyroidectomy) of 122 patients with different types of
      thyroid tumor. For most of the investigated parameters in different groups of
      patients, we did not find statistically significant differences. In the majority
      of cases, thyroid benign or malignant tumors were not accompanied by significant
      derangement of the gland selenoenzymes and of either intrathyroidal or plasma
      concentration of selenium. Nevertheless, types I and II iodothyronine deiodinases
      were the most promising (among selenoenzymes) targets for diagnoses and possibly
      therapy of thyroid tumors. Higher activities of both enzymes in cases with
      Graves' disease, as compared with other thyroid lesions, suggest their
      involvement in the pathogenesis of this condition. Patients with struna nodosa
      had higher levels of thyroid Zn, Cu, and Pb as compared with papillary carcinoma
      subjects and also a higher level of Cu than follicular carcinoma cases. The above
      diagnostics may play a similar role to some of the general thyroid function
      indices, TSH, anti-TG, anti-TPO, and calcitonin, which can partially distinguish
      between various thyroid tumors. In conclusion, some of selenium status markers,
      when accompanied with general parameters, and trace elements can serve as factors
      with pathophysiologic relevance and be helpful in the identification of malignant
      disease. Multivariate statistical methods should be employed to tackle a broad
      array of thyroid tumor diagnostic data in a short time. Partial least squares
      model and other pattern recognition methods seem to be the most appropriate
      methods for that task. The miniaturization of all the steps of complex analytical
      procedure should be developed in a way to allow its completion as sensitive,
      robust, and efficient for use of the small quantity of material provided by fine
      needle biopsy.

PMID- 19597723
TI  - The effects of copper sulfate on liver histology and biochemical parameters of
      term Ross broiler chicks.
AB  - Copper is an essential trace element that is extremely toxic to organisms and
      organs at high doses. We have investigated the histological and biochemical
      effects of a toxic dose of copper sulfate on the liver of term Ross broiler
      chicks. Fertilized eggs were divided into three groups: experimental, injected
      with 50 mcg/0.1 ml copper sulfate in the air chambers on day 1; sham, injected
      with 0.1 ml saline; and control, no injection. Term chicks were killed and their
      livers investigated histologically, with hematoxylin-eosin-stained sections
      examined under light microscopy, and biochemically, for malondialdehyde and
      glutathione levels. Histological examinations showed copper-treated samples with
      granular degeneration and necrosis of hepatocytes and impairment to the cell
      lining of the remark cords. The samples had a congestive appearance, with blood
      in the vena centralis and sinusoids, slight connective tissue increase, and
      lymphocyte infiltration. Control and sham group sections had normal appearances.
      As oxidative damage parameters, in the copper-treated group, malondialdehyde
      levels were increased and glutathione levels decreased. In the sham and control
      groups, there were no significant differences. At this toxic dose, copper sulfate
      shows oxidative damage according to the histology of term chick liver that are
      confirmed biochemically by the changes in malondialdehyde and glutathione levels.

PMID- 19597724
TI  - Autonomous innervation in renal inflammatory disease-innocent bystander or active
      modulator?
AB  - Increasing evidence suggests a significant interrelation between the autonomic
      nervous system and the immune system. The kidney is innervated by efferent
      sympathetic nerves as well as by peptidergic sensory afferent nerve fibers.
      Inflammation in the kidney may be affected by both types of fibers. Peptidergic
      "sensory" neurons might play a particularly important role: These fibers can
      induce local neurogenic inflammation via paracrine effects of their transmitters
      and evoke increased efferent sympathetic nerve outflow via their projections to
      the central nervous system. Several reports support the notion that renal
      innervation does indeed contribute to inflammation and sclerosis in kidney
      diseases. Hence, receptor antagonists interfering with the interaction of
      innervation and the immune system may prove useful to mitigate inflammatory
      processes in the kidney.

PMID- 19597725
TI  - Development and assessment of simple PCR markers for SNP genotyping in barley.
AB  - Simple molecular marker assays underpin routine plant breeding and research
      activities in many laboratories worldwide. With the rapid growth of single
      nucleotide polymorphism (SNP) resources for many important crop plants, the
      availability of routine, low-tech marker assays for genotyping SNPs is of
      increased importance. In this study, we demonstrate that temperature-switch PCR
      (TSP) supports the rapid development of robust, allele-specific PCR markers for
      codominant SNP genotyping on agarose gel. A total of 87 TSP markers for assessing
      gene diversity in barley were developed and used to investigate the efficacy for
      marker development, assay reliably and genotyping accuracy. The TSP markers
      described provide good coverage of the barley genome, are simple to use, easy to
      interpret and score, and are amenable to assay automation. They provide a
      resource of informative SNP markers for assessing genetic relationships among
      individuals, populations and gene pools of cultivated barley (Hordeum vulgare L.)
      and its wild relative H. spontaneum K. Koch. TSP markers provide opportunities to
      use available SNP resources for marker-assisted breeding and plant genetic
      research, and to generate information that can be integrated with SNP data from
      different sources and studies. TSP markers are expected to provide similar
      advantages for any animal or plant species.

PMID- 19597727
TI  - Solution to Mendeleyev vodka challenge.

PMID- 19597726
TI  - Drought stress and tropical maize: QTL-by-environment interactions and stability
      of QTLs across environments for yield components and secondary traits.
AB  - A recombinant inbred line (RIL) population was evaluated in seven field
      experiments representing four environments: water stress at flowering (WS) and
      well-watered (WW) conditions in Mexico and Zimbabwe. The QTLs were identified for
      each trait in each individual experiment (single-experiment analysis) as well as
      per environment, per water regime across locations and across all experiments
      (joint analyses). For the six target traits (male flowering, anthesis-to-silking
      interval, grain yield, kernel number, 100-kernel fresh weight and plant height)
      81, 57, 51 and 34 QTLs were identified in the four step-wise analyses,
      respectively. Despite high values of heritability, the phenotypic variance
      explained by QTLs was reduced, indicating epistatic interactions. About 80, 60
      and 6% of the QTLs did not present significant QTL-by-environment interactions
      (QTL x E) in the joint analyses per environment, per water regime and across all
      experiments. The expression of QTLs was quite stable across years at a given
      location and across locations under the same water regime. However, the stability
      of QTLs decreased drastically when data were combined across water regimes,
      reflecting a different genetic basis of the target traits in the drought and well
      watered trials. Several clusters of QTLs for different traits were identified by
      the joint analyses of the WW (chromosomes 1 and 8) and WS (chromosomes 1, 3 and
      5) treatments and across water regimes (chromosome 1). Those regions are clear
      targets for future marker-assisted breeding, and our results confirm that the
      best approach to breeding for drought tolerance includes selection under water
      stress.

PMID- 19597728
TI  - A sphingosine kinase inhibitor induces cell death in temozolomide resistant
      glioblastoma cells.
AB  - PURPOSE: Sphingosine kinase is an oncogene that is up-regulated in several solid
      tumors. The product of the sphingosine kinase activity, sphingosine-1-phosphate
      is a potent mitogen involved in diverse cell processes such as cell survival and
      migration. Current standard therapy in the treatment of glioblastoma multiforme
      (GBM) is a combination of surgery, radiation, and chemotherapy using the drug
      temozolomide (TMZ). However, virtually all tumors become resistant to TMZ.
      Therefore, new drug targets are necessary. In this study, we investigated whether
      inhibiting sphingosine kinase could induce cell death in TMZ-resistant GBM cells.
      METHODS: To study TMZ resistance in vitro, we have generated TMZ-resistant cell
      lines from established GBM cells. We used a potent inhibitor of sphingosine
      kinase to study its effect on colony formation and cell growth in GBM cells with
      a limited dilution and WST assay. Moreover, cell death was determined by
      measuring caspase-3 activity using flow cytometry. RESULTS: A sphingosine kinase
      inhibitor reduced cell colony formation and activated caspase-3 in both TMZ
      sensitive and resistant GBM cells. CONCLUSION: Addition of a sphingosine kinase
      inhibitor to the standard chemotherapy regimen against GBM may be beneficial.

PMID- 19597729
TI  - A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with
      previously treated advanced melanoma.
AB  - PURPOSE: Although much focus has been placed on immunotherapy for melanoma,
      further development of chemotherapy approaches is needed. Melanoma is responsive
      to platinum compounds and taxanes, but there is limited experience with
      combinations of these agents. Oxaliplatin has been reported to have detectable
      activity in melanoma, and a phase I study has identified a tolerable dose and
      schedule of oxaliplatin in combination with docetaxel and hematopoietic growth
      factor support. GM-CSF has a theoretical advantage of immune potentiation. These
      considerations supported the study of oxaliplatin, docetaxel, and GM-CSF in
      patients with advanced melanoma. METHODS: Eligibility included adequate organ
      function, PS<or=2, at most one prior chemotherapy and one prior immunotherapy, no
      prior treatment with oxaliplatin or taxanes and no chremophor allergy. After
      premedication, docetaxel was administered day 1 at 75 mg/m2, then oxaliplatin on
      day 2 at 85 mg/m2. GM-CSF (250 mcg/m2) was administered s.c. days 3-12. Cycles
      were 21 days in length, and disease reevaluation was performed every two cycles
      by RECIST criteria. RESULTS: Nineteen patients received at least one cycle, eight
      with one prior systemic therapy, five with two prior systemic therapies. Five
      patients did not complete two cycles and were not formally evaluable for
      response. Five patients had stable disease (SD), including one who failed two
      prior therapies and went on to receive ten cycles. The remaining nine patients
      displayed progressive disease (PD) after two cycles. Notable toxicities included
      seven cases (37%) of grade III/IV neutropenia and two (11%) hypersensitivity
      reactions. CONCLUSIONS: This combination of oxaliplatin, docetaxel, and GM-CSF
      has limited clinical activity in previously treated patients with advanced
      melanoma. Exploration in treatment-naive patients may still be warranted.

PMID- 19597730
TI  - Renal cell carcinoma presenting as Henoch-Schonlein purpura with leukocytoclastic
      vasculitis, hematuria, proteinuria and abdominal pain.
AB  - Some infectious, rheumatic, allergic diseases, and malignancies have been
      associated with leucocytoclastic vasculitis (LCV). LCV and cancer occur most
      frequently in patients with hematological malignancies such as lymphomas and
      leukemias. There have been a few prior cases reported of LCV associated with
      renal cell carcinoma (RCC). A 25-year-old male patient was referred from the
      department of dermatology and nephrology because of recurrent petechiae on both
      lower legs for several months; the patient also had a tumor of the left kidney.
      The findings on the skin biopsy were compatible with the diagnosis of LCV. The
      patient was diagnosed as having Henoch-Schonlein purpura (HSP) with LCV. A CT
      scan performed due to abdominal pain revealed a mass on the upper pole of the
      left kidney. A partial nephrectomy of the left kidney including the tumor was
      performed. The pathology report was consistent with a clear cell type of renal
      cell carcinoma, Fuhrman's grade 2; the tumor measured 0.9 x 0.8 cm and focal
      segmental glomerulosclerosis was noted in non-neoplastic regions. Here, we report
      a case of LCV associated with RCC presenting as HSP. This case illustrates the
      importance of evaluating patients for an underlying malignancy when HSP or LCV is
      diagnosed.

PMID- 19597731
TI  - Gynecomastia associated with low-dose methotrexate therapy for rheumatoid
      arthritis ameliorated by folate supplement.
AB  - A 62-year-old male with a 10-year history of seropositive rheumatoid arthritis
      (RA) developed gynecomastia 8 months after beginning oral low-dose methotrexate
      (MTX) therapy. Two months after folate supplementation, the gynecomastia symptoms
      improved. Gynecomastia associated with low-dose MTX is a rare occurrence, with
      only nine cases previously reported in the literature. This is the first report
      showing folate supplementation to be effective against gynecomastia following low
      dose MTX. Although it occurs infrequently, gynecomastia associated with low-dose
      MTX therapy should be considered in male patients with RA.

PMID- 19597732
TI  - Are anti-citrulline autoantibodies better serum markers for rheumatoid arthritis
      than rheumatoid factor in Thai population?
AB  - The aim of the study is to evaluate the prevalence of anti-citrulline antibodies
      (anti-CCP) versus rheumatoid factor (RF) in a cohort of Thai patients with
      rheumatoid arthritis (RA), a variety of rheumatic diseases other than RA and
      healthy controls. The association between anti-CCP and RA disease activity was
      also examined. Serum from 125 RA patients, 60 from other rheumatic diseases (non
      RA) and 60 from healthy controls were tested for IgM RF and second generation
      anti-CCP. The association between anti-CCP, RF, the Disease Activity Score (DAS
      28) and other relevant laboratory tests (CBC, ESR and CRP) were assessed. The
      sensitivity and specificity of anti-CCP antibody were 58.7 and 100% when compared
      with 63.5 and 98.3% for RF. These differences were not statistically significant.
      The anti-CCP outperformed RF in terms of the positive-predictive values (100 vs.
      97.6%); however, the negative-predictive values were 72.4% for RF and 69.6% for
      anti-CCP. The sensitivity when either anti-CCP or RF was positive increased to
      71.2%. Nine out of 45 RF-negative patients had a positive anti-CCP test. Anti-CCP
      was significantly correlated with parameters of inflammation, but not with DAS
      28. In conclusion, although anti-CCP is better than RF in distinguishing RA from
      other rheumatic diseases, its cost, which is 3.3 times higher than the RF test
      precludes it from replacing RF as a serum marker for Thai patients with RA. The
      treatment decisions cannot be based on the test alone, as it has no correlation
      with DAS 28. Its usefulness is in patients with suspected RA who have had a
      negative RF test.

PMID- 19597734
TI  - TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in Henoch
      Schonlein purpura with and without renal involvement.
AB  - Infections may trigger or aggravate glomerulonephritidis and renal vasculitis
      like Henoch Schonlein purpura (HSP). HSP is seen more frequently in patients with
      familial Mediterranean fever in which TLR-2 Arg753Gln polymorphism frequency is
      increased. Although renal involvement is the most important factor affecting the
      prognosis in HSP, it is not known which patients will have renal disease or why
      some patients have severe renal involvement while some others have mild renal
      disease. We investigated the role of TLR-2 and TLR-4 polymorphisms on the
      incidence and severity of renal involvement in HSP patients. We studied HSP
      patients with and without nephritis (n = 15 for each group) and healthy controls
      (n = 100). TLR-2 Arg753Gln and TLR-4 Asp299Gly/Thr399Ile polymorphisms were
      analyzed with polymerase chain reaction-restriction fragment length polymorphism
      method. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile
      polymorphisms in healthy controls were 1, 3, and 2%, respectively. The
      frequencies of these polymorphisms were not different in HSP patients with or
      without nephritis compared to healthy controls. TLR-2 Arg753Gln, TLR-4 Asp299Gly,
      and Thr399Ile polymorphisms are not increased in HSP or HSP nephritis patients.

PMID- 19597733
TI  - Adiponectin and leptin serum concentrations in patients with rheumatoid
      arthritis.
AB  - Adipose tissue is regarded as an active metabolic and endocrine organ producing
      adipokines. The purpose of the study was to evaluate adiponectin and leptin
      concentrations in rheumatoid arthritis (RA) patients (pts) in relation to disease
      duration and activity. The study group consisted of 80 RA pts. Serum adiponectin
      and leptin concentrations remained within normal ranges. Adiponectin
      concentration correlated positively both with the age and disease duration. Both
      adipokines levels correlated negatively with glomerular filtration rate. There
      were significant positive correlations between adipokines' concentrations and
      lipid profile components (between adiponectin and HDL-cholesterol, leptin and
      total cholesterol and LDL-cholesterol). In pts with long-standing RA, there was a
      negative correlation between adiponectin and numbers of tender, swollen joints
      and a positive relationship between leptin level and DAS28. The results confirm
      adipokines' involvement in the process of inflammation and atherosclerosis:
      protective and antiinflammatory adiponectin effect and proatherogenic and
      proinflammatory leptin function.

PMID- 19597735
TI  - Lymphovascular invasion in radical cystectomy specimen: is it an independent
      prognostic factor in patients without lymph node metastases?
AB  - PURPOSE: To determine the prognostic significance of lymphovascular invasion
      (LVI) in patients with urothelial carcinoma of the bladder undergoing radical
      cystectomy (RC) and bilateral pelvic lymph node dissection. METHODS: From 1992 to
      2008, 526 patients underwent RC and pelvic lymphadenectomy at our institution by
      a single surgical team. All relevant data were entered into a database and
      analyzed. LVI was defined as "the presence of tumor cells within an endothelial
      lined space." The exclusion criteria were non-TCC histology, salvage cystectomy,
      neoadjuvant chemotherapy, and unknown LVI status. RESULTS: A total of 357
      patients met the inclusion criteria. Overall prevalence of LVI was 29%. LVI was
      significantly associated with higher T stage, lymph node (LN) metastases, and
      higher grade. Patients with LVI had significantly higher recurrence rate (P <
      0.001) and decreased long-term survival (P < 0.001). In patients without LN
      metastases, LVI in the primary led to a significantly decreased recurrence-free
      (P = 0.003) and disease-specific survival (P = 0.001). In the presence of LN
      metastases, LVI did not significantly alter the recurrence-free or disease
      specific survival. On multivariate analysis, T stage (P < 0.0001) and LN
      metastases (P = 0.01) were significant independent prognostic factors influencing
      disease-specific survival. LVI did not have independent prognostic value. T stage
      was the only significant prognostic factor in the lymph node negative group.
      CONCLUSIONS: Although, the presence of LVI in node-negative patients is an
      adverse prognostic factor on univariate analysis of disease-specific survival, it
      is not an independent prognostic factor on multivariate analysis. Pathological
      stage is the only independent prognostic factor for survival.

PMID- 19597736
TI  - Antiphonal call timing in marmosets is behaviorally significant: interactive
      playback experiments.
AB  - Studies of primate vocal communication systems have generally focused on
      vocalizations and the information they convey to conspecifics. But the
      vocalizations are not the only sources of information. Aspects of each species
      vocal behaviors are likely to be communicatively rich as well. During vocal
      interactions, for example, the latency delay between the calls could communicate
      an important message to the signal receiver, such as an interest and willingness
      to socialize. Here we employed novel, interactive playback software to address
      this issue in the antiphonal calling behavior of common marmosets. In these
      experiments, we parametrically varied the latency delay of antiphonal call
      stimuli and measured its effects on subjects' resultant vocal behavior. Results
      showed that marmosets produced successively fewer antiphonal call responses
      during test conditions with increasing latency delays. Moreover, although
      subjects produced significantly more antiphonal than spontaneous calls in
      conditions with antiphonal call timing delays up to 9 s, a longer delay resulted
      in a significant decline in calling. These data suggest that antiphonal call
      timing is a salient cue for maintaining antiphonal calling interactions and may
      be used by marmosets to determine whether a subsequent call is produced in
      response to or independently of their own.

PMID- 19597737
TI  - The common pig: a possible model for teaching ear surgery.
AB  - Anatomical dissection of the human temporal bone is an essential element in the
      education of ear surgeons. Unfortunately, the acquisition of human temporal bones
      can be difficult. As an alternative, temporal bones of animals might help. The
      temporal bones of ten common pigs taken out of a butcher's daily routine were
      drilled and dissected under clinical aspects. The resulting anatomy was analyzed
      and measured. Especially, the mastoid, the external ear canal and the middle ear
      were incorporated. The preparation was done following a strict order of steps
      relevant to typical work of an ENT surgeon. Our results were compared with known
      data of the human temporal bone and effectiveness concerning surgical training
      was verified. We could see that the temporal bone of the pig had a totally
      different appearance compared to the human one, especially regarding the length
      and location of the external ear canal. Also, the mastoid is difficult to
      identify. It is hidden by the atlanto-occipital joint and has no pneumatization.
      The anatomical landmarks as the arcades and the facial nerve are congruent to the
      human anatomy although not all structures are accessible via the mastoid. The
      pigs' middle ear showed to be very similar to the human one. The incus showed a
      shortened long process. This study showed that the temporal bone of the pig might
      be an alternative regarding some aspects of surgical training in ENT education. A
      complete replacement is not possible. After some modification, it might be an
      efficient model for endaural techniques and ossicular manipulation.

PMID- 19597738
TI  - The effect of active sonar for the protection of moored and anchored warships on
      the human hearing.
AB  - This study wants to show the effects of active middle frequency sonar on a
      selected group of Italian Navy divers. Ten male divers with normal hearing were
      exposed to active sonar of the Italian Navy for more than 100 exposures, each of
      at least 1-h duration, in the course of 6 months. Before, at the end, and six
      months after the end of noise exposure, we performed pure-tone audiometry,
      Carhart test, Peyser test, thresholds of discomfort test (TDT), tympanometry,
      transient evoked otoacoustic emissions (TEOAE), distortion product otoacoustic
      emissions (DPOAE), and auditory brainstem response (ABR). At the end of the noise
      exposure, the audiological tests showed a worsening of the mean air and bone
      audiometric thresholds at the 2,000 (1/10), 4,000 (7/10), and 8,000 Hz (6/10); a
      fail status of the TEOAE and DPOAE, which were previously present, in all the
      divers; temporary threshold shift, at the Peyser test, in 9/10 divers; discomfort
      for pulse tone presented at the TDT test, in all the divers; no post exposure
      significant differences at the Carhart and ABR tests, in any of the divers. Six
      months after the end of noise exposure, all the divers presented a complete
      recovery of their audio-vestibular functions. Our results show the temporary
      negative effects of repeated and lasting exposure to active sonar (Hull MF) on
      the divers; the last control demonstrate the absence of permanent noise-induced
      hearing loss in divers exposed to active sonar.

PMID- 19597739
TI  - Interaction of ion tracks in spatial and temporal proximity.
AB  - In the present work, a systematic analysis of the impact of spatial and temporal
      proximity of ion tracks on the yield of higher-order radiolytic species as well
      as of DNA damage patterns is presented. This potential impact may be of concern
      when laser-driven particle accelerators are used for ion radiation therapy. The
      biophysical Monte Carlo track structure code PARTRAC was used and, to this end,
      extended in two aspects: first, the temporal information about track evolution
      has been included in the track structure module and, second, the simulation code
      has been modified to enable parallel multiple track processing during simulation
      of subsequent modelling stages. Depending on the spatial and temporal separation
      between ion-track pairs, the yield of chemical species has been calculated for
      incident protons with start energies of 20 MeV, for He(2+) ions with start
      energies of 1 and 20 MeV, and for 60 MeV C(6+) ions. Provided the overlap of the
      considered ion tracks is sufficient in all four dimensions (space and time), the
      yield of hydroxyl radicals was found to be reduced compared to that of single
      tracks, for all considered ion types. The biological endpoints investigated were
      base damages, single-strand breaks, double-strand breaks, and clustered lesions
      for incident pairs of protons and He(2+) ions, each with start energies of 20
      MeV. The yield of clustered lesions produced by 20 MeV protons turned out to be
      influenced by the spatial separation of the proton pair; in contrast, no
      influence was found for different start times of the protons. The yield of single
      strand breaks and base hits was found neither to depend on the spatial separation
      nor on the temporal separation between the incident protons. For incident 20 MeV
      He(2+) ions, however, a dependence on the spatial and temporal separation of the
      ion pair was found for all considered biological endpoints. Nevertheless, spatial
      proximity conditions where such intertrack effects were obtained are not met in
      the case of tumour radiation therapy; thus, no impact on radiation effects due to
      short pulse duration of laser-driven accelerators can be expected from
      alterations during the chemical stage.

PMID- 19597740
TI  - Different properties of VEGF-antagonists: Bevacizumab but not Ranibizumab
      accumulates in RPE cells.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) antagonists are currently
      the therapy of choice for age-related macular degeneration. Here we compared the
      effects of FDA-approved Ranibizumab and off-label used Bevacizumab on RPE cells,
      investigating their respective uptake by RPE cells over time. METHODS: Primary
      porcine RPE cells were treated with Bevacizumab or Ranibizumab, respectively.
      Uptake of the respective VEGF-antagonists was assessed with confocal laser
      scanning microscopy and flow cytometry. Cell death was assessed with MTT assay
      and VEGF secretion was measured with ELISA. RESULTS: When clinical doses were
      applied for 1 h, Bevacizumab was taken up by RPE cells as assessed by confocal
      laser scanning microscopy and flow cytometry. After 24 h of incubation, and
      further assessed after 1d, 5d, and 7d, Bevacizumab was detected in RPE cells
      where it accumulated over time. The presence of Bevacizumab within RPE cells
      after 7d was confirmed by flow cytometry. While some Ranibizumab was found in RPE
      cells after 1 h of incubation when assessed with confocal laser microscopy but
      not by flow cytometry, no signal above control was detected after 1d, 5d, or 7d.
      Neither substance induced significant cell death after 7 days and no inhibitory
      effect on VEGF secretion was observed after day 3 of culture. CONCLUSIONS:
      Bevacizumab, but not Ranibizumab, accumulates in RPE cells over time, implying
      substantial differences between these two drugs.

PMID- 19597741
TI  - Relationship between muscle coordination and racket mass during forehand drive in
      tennis.
AB  - This study aimed at investigating the relationship between the trunk and upper
      limb muscle coordination and mass of the tennis racket during forehand drive. A
      total of 15 male tennis players performed seven series of ten crosscourt forehand
      drives, both with their personal racket and six rackets with increased mass
      ranging from 6 to 16% (step = 2%) of their personal racket mass. The
      electromyographic (EMG) activity was recorded from nine trunk and upper limb
      muscles. The onset before impact and EMGrms values of the bursts were
      individually calculated. Results showed that the ball speed and the muscle
      activation temporal sequences were similar, whatever the increase in racket mass.
      Interestingly, in all participants, the activation level of the pectoralis major,
      latissimus dorsi and biceps brachii decreased when the racket mass increased,
      while the variations in the anterior deltoid activation level were correlated to
      the individual personal racket mass. These findings strongly suggest that the
      study of muscle activity during tennis practice should be considered as a
      complementary technique to determine a better adequacy of the racket
      characteristics to those of the player.

PMID- 19597743
TI  - Competing discourses in palliative care.
AB  - BACKGROUND: Palliative care focuses on early identification as well as prevention
      and alleviation of suffering. Previous studies have established that palliative
      care is a disciplinary area in a state of transformation due to the involvement
      of different professional categories and that nursing care in the palliative
      context is influenced by the dominance of the medical perspective. AIM: This
      study aimed to describe palliative care from a nursing perspective prior to the
      implementation of a palliative care programme. PATIENTS AND METHODS: The approach
      was inspired by the ethnographic method and a constructionist perspective was
      used as a theoretical framework, as the focus was on existing palliative care
      discourses. Field studies were conducted on a ward where palliative care was
      provided to patients at the end of life. Approval for the study was granted by
      the Ethics Committee at Sahlgrenska Academy. Data were collected by means of
      participant field studies, informal deliberations and other relevant documents.
      MAIN RESULTS: Four different discourses were discerned: caring, non-caring,
      curing and the organisation. CONCLUSIONS: The ethos on the ward was strongly
      linked to the medical discourse. We consider that a prerequisite for the
      organisation of palliative care is an expressed caring perspective based on the
      patients' experiences of suffering, which perspective is lacking in the curing
      and organisational discourses.

PMID- 19597742
TI  - Production and characterization of monoclonal antibody and its recombinant single
      chain variable fragment specific for a food-born mycotoxin, fumonisin B1.
AB  - Fumonisin B(1) (FMB(1)) is a food-born mycotoxin produced by Fusarium
      moniliforme. Monoclonal antibody against FMB(1) (anti-FMB(1) mAb) was produced in
      the hybridoma DV9, which was established from a BALB/c mouse immunized with
      bovine serum albumin conjugated FMB(1) (FMB(1)-BSA). A competitive direct enzyme
      linked immunosorbent assay (ELISA) showed that anti-FMB(1) mAb has about 10 ppb
      of minimum FMB(1) detection concentration and 220 ppb of 50% inhibition
      concentration (IC(50)). Much lower cross-reactivity of anti-FMB(1) mAb on
      ochratoxin A, aflatoxin B(1) and deoxynivalenol provided that anti-FMB(1) mAb was
      specific for FMB(1). The gene coding single chain variable fragment against
      FMB(1) (anti-FMB(1) scFv) was cloned from the hybridoma DV9 and was expressed in
      recombinant Escherichia coli. Insoluble anti-FMB(1) scFv required optimization of
      its refolding condition, and hence functional scFv was obtained. By using
      indirect ELISA, about 12-fold lower binding activity of anti-FMB(1) scFv on
      FMB(1)-BSA was obtained in comparison with that of the parental mAb.

PMID- 19597744
TI  - An experimental and theoretical approach to the molecular structure of 2-(4-[3
      (2,5-dimethylphenyl)-3-methylcyclobutyl]thiazol-2-yl)isoindoline-1,3-dione.
AB  - The title compound, 2-{4-[3-(2,5-dimethylphenyl)-3-methylcyclobutyl]thiazol-2
      yl}isoindoline-1,3-dione (C(24)H(22)N(2)O(2)S), was synthesized and characterized
      by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound
      crystallizes in the monoclinic space group P2(1)/c with a = 19.7799(13) A, b =
      6.7473(4) A, c = 15.7259(9) A and beta = 103.416(5) degrees . In addition, the
      molecular geometry, vibrational frequencies and gauge including atomic orbital
      (GIAO) (1)H and (13)C chemical shift values of the title compound in the ground
      state have been calculated by using the Hartree-Fock (HF) and density functional
      method (DFT/B3LYP) with 6-31G(d), 6-31 + G(d,p) and LANL2DZ basis sets, and
      compared with the experimental data. To determine conformational flexibility,
      molecular energy profile of the title compound was obtained by semi-empirical
      (AM1) calculations with respect to two selected degrees of torsional freedom,
      which were varied from -180 degrees to +180 degrees in steps of 5 degrees .
      Besides, molecular electrostatic potential, frontier molecular orbitals (FMO)
      analysis and thermodynamic properties of the title compound were investigated by
      theoretical calculations.

PMID- 19597745
TI  - Safety and bio-effects of ultrasound contrast agents.
AB  - The use of gas-filled microbubbles as ultrasound contrast agents raises potential
      safety concerns for diagnostic ultrasound imaging. A number of biological effects
      have been seen in experimental systems, including the induction of physiological
      response to cardiac exposures (premature ventricular contractions) and damage at
      a microvascular level (microvascular rupture and petechial haemorrhage). The
      literature indicates that a mechanical index (MI) of 0.4 represents the threshold
      above which microvascular bio-effects are seen in in vivo studies. Above this
      value, the extent of biological effects appears to increase rapidly with both
      increasing in situ peak negative acoustic pressure amplitude and with contrast
      agent concentration. While there is no proven evidence of harm resulting from
      clinical use of these agents, caution is recommended when contrast-enhanced
      imaging is undertaken.

PMID- 19597746
TI  - Who initiates emergency commitments?
AB  - Florida's Mental Health Act was amended in 2005 and 2006 to include licensed
      mental health counselors and licensed marriage and family therapists,
      respectively, to the list of professionals authorized to initiate emergency
      commitments. The present study evaluates the volume of involuntary emergency
      commitments by type of initiator for a 5 year period. The results indicate that
      allowing licensed mental health counselors and licensed marriage and family
      therapist to initiate emergency commitments has not been related to increased
      numbers of emergency commitments or a higher proportion of emergency commitments
      being initiated by mental health professionals. Potential policy and fiscal
      implications, as well as future directions for research, are discussed.

PMID- 19597749
TI  - Coffee and black tea consumption and risk of breast cancer by estrogen and
      progesterone receptor status in a Swedish cohort.
AB  - BACKGROUND: Coffee and tea consumption has been inconsistently associated with
      the risk of breast cancer. We examined the associations of caffeinated coffee and
      black tea consumption with the incidence of breast cancer, overall and by
      estrogen receptor (ER) and progesterone receptor (PR) status of the tumor, in the
      Swedish Mammography Cohort. METHODS: We prospectively followed up 61,433 women
      who were cancer free at baseline in 1987-1990. Coffee and tea consumption was
      assessed with a food-frequency questionnaire administered at baseline and in
      1997. Incident invasive breast cancer cases were ascertained by linkage with
      Swedish Cancer registers. RESULTS: Over a mean follow-up of 17.4 years, through
      December 2007, there were 2,952 incident cases of invasive breast cancer
      identified. Coffee consumption was not associated with risk of overall breast
      cancer (multivariate relative risk (RR) for >= 4 cups/day versus <1 cup/day =
      1.02; 95% CI, 0.87-1.20) or with any subtype defined by ER and PR status. Black
      tea consumption was significantly positively associated with risk of overall
      breast cancer and ER+/PR+ tumors. The multivariate RRs comparing >= 2 cups/day of
      tea with no consumption were 1.22 (95% CI, 1.05-1.42) for overall breast cancer
      and 1.36 (95% CI, 1.09-1.69) for ER+/PR+ tumors. CONCLUSION: Findings from this
      prospective study do not support a role of coffee consumption in the development
      of breast cancer but suggest that black tea consumption may be positively
      associated with risk of ER+/PR+ tumors.

PMID- 19597750
TI  - Cancer risk factors associated with insulin-like growth factor (IGF)-I and IGF
      binding protein-3 levels in healthy women: effect modification by menopausal
      status.
AB  - Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) appear
      to influence breast cancer risk and are hypothesized to mediate the effects of
      several cancer risk factors that depend on menopausal status. We investigated
      associations among cancer risk factors and plasma IGF-I and IGFBP-3 in 882
      healthy control women (426 premenopausal, 456 postmenopausal) from two population
      based breast cancer case-control studies. Interactions with menopausal status
      were statistically tested. We observed associations with non-modifiable (age,
      benign breast disease) and modifiable factors [body mass index (BMI), physical
      activity, smoking habits, alcohol consumption]. Furthermore, we demonstrated
      statistical interactions with menopausal status. Premenopausal IGFBP-3 levels
      increased and postmenopausal levels decreased with age (p-interaction = 0.001).
      Overweight postmenopausal women had higher IGF-I (p = 0.049) and IGFBP-3 (p =
      0.005) levels than women with lower BMI. Postmenopausal IGF-I levels were
      positively associated with physical activity (p-trend = 0.012, p-interaction =
      0.050). Postmenopausal current smokers had lower IGF-I (p = 0.014) and IGFBP-3
      levels (p = 0.011). Increasing alcohol consumption was associated with lower
      premenopausal IGF-I (p-trend = 0.002, p-interaction = 0.004) and higher
      postmenopausal IGFBP-3 levels (p = 0.019). Benign breast disease was associated
      with higher premenopausal (p = 0.044) and postmenopausal (p = 0.002) IGF-I
      levels. IGF-I and/or IGFBP-3 potentially mediate changes in breast cancer risk
      associated with BMI, benign breast disease, and perhaps alcohol consumption.
      Other observed associations suggest that neither IGF-I nor IGFBP-3 alone acts as
      mediator. Consideration of menopausal status may help disentangle carcinogenic
      pathways involving IGF proteins.

PMID- 19597748
TI  - Dose and timing effect of etomidate on motor evoked potentials elicited by
      transcranial electric or magnetic stimulation in the monkey and baboon.
AB  - OBJECTIVE: Etomidate has been shown to both enhance and depress the cortical
      amplitude of somatosensory evoked potentials (SSEP) depending on the dose used.
      Similar amplitude increases with etomidate and motor evoked potentials resulting
      from cortical magnetic (tcMMEP) and electric (tcEMEP) stimulation have not been
      consistent. We used a primate model to elucidate the time and dose
      characteristics of the effect. METHODS: tcMMEP and tcEMEP were characterized
      during bolus injections of 0.1-1.8 mg/kg etomidate in 10 adult cynomologous
      monkeys during a baseline anesthesia with a continuous ketamine infusion.
      Responses were assessed by measuring the amplitude and onset latency of the
      hypothenar compound action potential response. In a second experiment the
      epidural and hypothenar response to tcEMEP was recorded under 0.3% isoflurane
      anesthesia and following intravenous injection of 0.05-0.35 mg/kg etomidate.
      Cortical stimulation was accomplished using a Cadwell MES-10 (tcMMEP) and
      Digitimer D180 (tcEMEP). RESULTS: The amplitude of the hypothenar muscle response
      was increased for tcEMEP and tcMMEP at 20 min following 0.1 mg/kg etomidate in
      the monkey. The amplification of the tcMMEP response was significantly greater
      than the tcEMEP response (1.95 + 0.62 SD vs. 1.43 + 0.68 SD, P = 0.023).
      Responses at higher doses were all below baseline. The tcMMEP response was
      significantly smaller than the tcEMEP at doses above 0.9 mg/kg (all P<0.001). The
      onset latency values were not significantly increased at any dose or time. The
      epidural recording demonstrated a large increase in the number of I waves
      compared to the isoflurane baseline. CONCLUSIONS: This study demonstrates that a
      low dose (0.1 mg/kg) of etomidate increases the com- pound muscle action
      potential (CMAP) amplitude for tcEMEP and tcMMEP in the monkey whereas higher
      doses decrease the amplitude. Epidural recordings demonstrate a marked increase
      in the number of I waves consistent with a cortical effect similar to the
      postulated effect that results in amplification of the cortical SSEP. This
      suggests the amplitude loss in the hypothenar muscles may be due to depression of
      the spinal cord by etomidate. The CMAP response amplification at low doses was
      greater in tcMMEP than tcEMEP and the depression at higher doses was more with
      the tcMMEP technique consistent with the greater dependence of the tcMMEP
      technique on synaptic activation.

PMID- 19597747
TI  - Exploring predictors of outcome in the psychosis prodrome: implications for early
      identification and intervention.
AB  - Functional disability is a key component of many psychiatric illnesses,
      particularly schizophrenia. Impairments in social and role functioning are linked
      to cognitive deficits, a core feature of psychosis. Retrospective analyses
      demonstrate that substantial functional decline precedes the onset of psychosis.
      Recent investigations reveal that individuals at clinical-high-risk (CHR) for
      psychosis show impairments in social relationships, work/school functioning and
      daily living skills. CHR youth also demonstrate a pattern of impairment across a
      range of cognitive domains, including social cognition, which is qualitatively
      similar to that of individuals with schizophrenia. While many studies have sought
      to elucidate predictors of clinical deterioration, specifically the development
      of schizophrenia, in such CHR samples, few have investigated factors relevant to
      psychosocial outcome. This review integrates recent findings regarding cognitive
      and social-cognitive predictors of outcome in CHR individuals, and proposes
      potential directions for future research that will contribute to targeted
      interventions and improved outcome for at-risk youth.

PMID- 19597751
TI  - Small ruminant production in Turkey: highlighting in goat production.
AB  - This paper deals with the effects of structural, governmental and socio-economic
      conditions linked to small ruminant production, especially goat production. The
      number of small ruminants in Turkey fell from almost 51,530 in 1990, to 31,761 in
      2007. In 1990, the number of small ruminants started to decrease due to
      structural, genetic and economic reasons such as a lack of state support
      policies, high costs of inputs, poor performance of local breeds, socio-economic
      conditions, and migration. In Turkey, the socio-economic and geographical
      structure make small ruminant production an important profession; it is also a
      significant source of income in rural regions. 35% of red meat and 12% of milk
      production is obtained from small ruminants. Although, Turkey has the highest
      goat population among its border and EU countries, ranks low with milk
      production. Reasons for the present situation are well evaluated; changes and
      tendencies in sheep and goat production as well as milk and meat production that
      are examined and associated with the population of Turkey are widely discussed.
      In addition, in order to improve the present situation, some technical and
      structural suggestions are mentioned.

PMID- 19597752
TI  - Exogenous cMHM regulates the expression of DMRT1 and ER alpha in avian testes.
AB  - The male hypemethylated (MHM) region, associated with sex-specific DNA
      methylation and histone acetylation, encodes non-coding RNAs that are expressed
      exclusively on Z chromosome in female chickens. The function of the MHM non
      coding RNAs is unclear yet. In order to analyze the regulation effect of MHM on
      mRNA expression of sex-dependent genes, exogenous plasmid containing chicken MHM
      (cMHM) was constructed and injected into left testes of 13-week-old roosters.
      Comb color of the roosters in the pEGFP-N1-cMHM group became much paler, an
      indication of change in sex hormones, as compared with that of the negative
      control groups at the 10 days after injection. Real-time PCR was used to
      determine mRNA expression of sex-dependent genes in testes tissue. Transcription
      of ER alpha gene was significantly up-regulated in the pEGFP-N1-cMHM group
      compared with that of the pEGFP-N1 and normal saline groups (P < 0.01), while
      expression of DMRT1 mRNA declined severely in the pEGFP-N1-cMHM group compared
      with that of normal saline groups (P < 0.05). Nevertheless, expression of other
      candidate genes, such as AMH, FOXL2, SOX9, and P450arom did not change after
      injection of exogenous cMHM. In conclusion, down-regulation of DMRT1 and up
      regulation of ER alpha in rooster testes treated with exogenous pEGFP-N1-cMHM
      plasmid might indicate a novel cMHM non-coding RNA-mediated mechanism in avian
      sex differentiation.

PMID- 19597753
TI  - Computerized preoperative planning for correction of sagittal deformity of the
      spine.
AB  - PURPOSE: Various methods of preoperative planning have been described for the
      correction of spinal sagittal deformities. They are reliable on condition that
      the thoracolumbar spine is totally fused and enable only the simulation of
      pedicle subtraction osteotomy (PSO). In this study, a new theoretical planning
      that can be used regardless of the etiology of the deformity and the type of
      osteotomy is described and assessed. METHODS: The spino-pelvic sagittal balance
      can be expressed by two parameters: pelvic tilt (PT) and center of both acoustic
      meati (CAM) overhang. These two parameters vary according to the type, number,
      level, and angulation of osteotomies. The general principle of the planning is to
      define the surgical program in order to obtain PT and CAM overhang as close as
      possible to the normal values. The theoretical planning is based on a
      trigonometric construction which depends on numerous factors and is challenging
      to use in daily practice without the aid of a software tool. Modifications are
      proposed if the spine cannot be modeled as a solid beam due to unfused disks
      allowing relative motion. The SpineView software, which enables analysis and
      quick visualization of different correction possibilities, is presented. The
      planning method is assessed in a prospective cohort of 11 patients by comparing
      planned values of spino-pelvic parameters to postoperative values. RESULTS: In
      all, 8 preoperative plans out of 11 were concordant with the postoperative
      results. CONCLUSIONS: The preoperative planning enables the surgeon to estimate
      the clinical effects of the different surgical techniques in order to choose the
      best procedure for a given patient.

PMID- 19597754
TI  - Neurovascular details about forearm muscles: applications in their clinical use
      in functional muscular transfer.
AB  - PURPOSE: The concept of muscle subunits has been introduced for limb
      reconstruction and functional conservation of donor site, yet it requires
      thorough understanding of neurovascular anatomy of muscles. The present study
      provides neurovascular details of forearm skeletal muscles. METHODS: Twenty-eight
      forearms were dissected totally, ten for observing extramuscular nerve
      distribution, ten for observing intramuscular nerve distribution by modified
      Sihler's technique, and the other eight for observing intramuscular artery
      distribution by aqueous barium sulfate infusion. The forearm muscles were
      classified into three different types according to Lym's classification. Numbers
      of extramuscular and intramuscular nerves were counted and compared between the
      types. Intramuscular vascular distribution was also classified into three
      different types according to Mathes' method. Intramuscular vascular distribution
      was compared with nerve distribution as well. RESULTS: There were also some
      variations in the composition of muscular branches. Numbers of intramuscular
      nerve branches were significantly higher in muscle types IIa and III. Morphology
      and intramuscular neurovascular distribution of type II muscles are easy to split
      into two independent parts for functional muscular flap transfer according to
      morphology and intramuscular neurovascular distribution. CONCLUSIONS: The present
      study elucidated that flexor carpi ulnaris and radialis, extensor carpi ulnaris,
      and carpi radialis brevis were suitable for functional muscular transfer from
      several different insights, but the roles of pronator teres and supinator
      remained to be controversial. This study might be very helpful to plastic
      surgeons and anatomists.

PMID- 19597755
TI  - Clinical implications of the echocardiographic assessment of left ventricular
      long axis function.
AB  - The assessment of the left and right ventricular long axis function by Doppler
      echocardiography was started many years ago with the use of M-mode. Two
      dimensional echocardiography was subsequently used to study the longitudinal
      function of the left ventricle. The studies of that era led to useful
      conclusions. However, tissue Doppler imaging, a relatively new echocardiographic
      technique, recently became the first choice for such an assessment. Moreover, the
      advances of tissue tracking and strain rate also have an important contribution.
      New studies were conducted and new data derived for left and right ventricular
      function in various cardiac diseases. The aim of this review was to present the
      accumulated knowledge of the Doppler echocardiography study of the left
      ventricular long axis function and the relevant clinical implications.

PMID- 19597756
TI  - In-hospital outcomes after elective and non-elective percutaneous coronary
      interventions in hospitals with and without on-site cardiac surgery backup.
AB  - BACKGROUND: Guidelines recommend on-site surgery backup (SB) when elective
      percutaneous coronary intervention (PCI) is performed. The evidence for this
      recommendation is however weak. OBJECTIVES: The objective of the present study
      was to compare clinical outcomes in patients undergoing PCI in hospitals with SB
      or without surgery backup (non-SB). METHODS: Prospective German PCI registry in
      36 hospitals throughout Germany. Consecutive procedures were collected and
      analyzed centrally. RESULTS: In 2006, a total of 23,148 patients were included;
      12,465 patients (53.8%) in 11 hospitals with SB and 10,683 patients (46.2%) in 25
      hospitals without on-site cardiac SB. Both patient groups were well-balanced with
      regard to age and gender. SB hospitals had more patients with ACS (OR 1.29; 95%CI
      1.23-1.36) and less patients with stable angina (OR 0.78; 95%CI 0.74-0.82) than
      non-SB hospitals. There was no indication of a clinically relevant differential
      outcome for in-hospital death, MACE, non-fatal MI, non-fatal stroke/TIA, or
      emergency CABG between SB and non-SB hospitals for neither patients with ACS nor
      stable angina except for emergency CABG in ACS patients (more frequent in SB
      hospitals, OR 2.29; 95%CI 1.02-5.13). CONCLUSIONS: There was no evidence of an
      excess risk associated with PCI-procedures performed in non-SB hospitals.

PMID- 19597757
TI  - Attenuation of myocardial injury by postconditioning: role of hypoxia inducible
      factor-1alpha.
AB  - Postconditioning (PostC) has regenerated interest as a mechanical intervention
      against myocardial ischemia/reperfusion injury, but its molecular mechanisms
      remain elusive. This study tested the hypothesis that hypoxia inducible factor
      1alpha (HIF-1alpha) plays a role in PostC-induced cardioprotection. Male Wistar
      rats were subjected to 30 min ischemia followed by 3 h of reperfusion (Control).
      PostC with 3 cycles of 10 s reperfusion and 10 s re-occlusion was applied at the
      onset of reperfusion. Relative to the Sham group, HIF-1alpha protein level was
      increased by 2.9-fold in the Control group, but its level was enhanced by 5.8
      fold with PostC (P < 0.01 vs. Control). However, HIF-1alpha protein level was
      further augmented by 2.0-fold and 3.3-fold, respectively, when the prolyl
      hydroxylase inhibitor, dimethyloxalylglycine (DMOG, 40 mg/kg, i.p.) was given at
      24 h before ischemia in both Control and PostC groups. PostC reduced infarct size
      by 24% compared with the Control (27 +/- 4.2% vs. 36 +/- 5.2%, P < 0.01),
      consistent with significant lower levels of plasma creatine kinase activity,
      index of cardiomyocyte apoptosis and caspase-3 activity. Although pretreatment
      with DMOG significantly reduced infarct size relative to the Control, the infarct
      sparing effect of PostC was remarkably enhanced when DMOG was given before PostC
      (18 +/- 2.0% vs. 27 +/- 4.2% in PostC alone, P < 0.05). There was a significant
      linear inverse relationship between HIF-1alpha protein level and infarct size (r
      = -0.799, P < 0.01) among all groups. Furthermore, along with up-regulated HIF
      1alpha expression, the levels of iNOS mRNA and protein were significantly
      increased in the PostC alone and DMOG plus PostC groups. In conclusion, these
      data suggest that HIF-1alpha is involved in cardioprotection by PostC and
      pharmacological augmentation of HIF-1alpha expression that enhances the infarct
      sparing effect of PostC; iNOS, the downstream gene of HIF-1alpha, may participate
      in signaling pathways in mediating PostC's protection.

PMID- 19597758
TI  - Comparison between emergency and elective endoscopic sphincterotomy in patients
      with acute cholangitis due to choledocholithiasis: is emergency endoscopic
      sphincterotomy safe?
AB  - PURPOSE: We retrospectively assessed post-EST complications and examined whether
      combination therapy comprising endoscopic biliary drainage (EBD) plus endoscopic
      sphincterotomy (EST) as the initial treatment is safe in patients with acute
      cholangitis due to choledocholithiasis. METHODS: Among the 363 consecutive
      patients with acute cholangitis due to choledocholithiasis who were treated in
      our hospital between December 1992 and December 2006, the subjects comprised 127
      patients with moderate acute cholangitis for whom EBD and EST were carried out.
      Factors influencing risk factors for post-EST pancreatitis, hemorrhage and
      hospitalization were determined by multivariate analysis. RESULTS: Multivariate
      analysis revealed that only precut sphincterotomy (PST) was a significant risk
      factor for post-EST pancreatitis, and the incidence of pancreatitis in patients
      who underwent PST was significantly higher than that in those who did not (P =
      0.041). Only age was a significant risk factor for post-EST hemorrhage, and
      younger patients were likely to experience hemorrhage after EST (P = 0.021).
      Total bilirubin and the timing of EST were significant factors associated with
      hospitalization. Hospitalization in patients who underwent EBD plus EST as the
      initial treatment (emergency EST) was significantly shorter than that in those
      who palliatively underwent EST after EBD (elective EST; 11.8 vs. 16.2 days, P =
      0.001). CONCLUSIONS: Combination therapy comprising EBD plus EST as the initial
      treatment for patients with moderate acute cholangitis due to choledocholithiasis
      was safe and did not prolong the period of hospitalization.

PMID- 19597759
TI  - Apoptotic effect of sonodynamic therapy mediated by hematoporphyrin monomethyl
      ether on C6 glioma cells in vitro.
AB  - PURPOSE: Sonodynamic therapy (SDT) is a new method for treating cancer by
      inducing cell necrosis and/or apoptosis. However, the molecular mechanisms of
      cell apoptosis after SDT treatment remain unclear. In this study we investigated
      the apoptotic effect and mechanisms of SDT mediated by hematoporphyrin monomethyl
      ether (HMME) on C6 glioma cells in vitro. METHODS: The time of ultrasound
      irradiation was optimized by MTT. The apoptotic rate, generation of ROS (reactive
      oxygen species), and mitochondrial membrane potential (MMP) were detected by flow
      cytometry, and expressions of apoptosis proteins were measured by Western blot
      after SDT treatment. RESULTS: The results displayed that treatment of C6 glioma
      cells with SDT resulted in the occurrence of apoptosis, which was associated with
      the production of ROS and loss of MMP. The results also showed that protein
      expression of Bax, caspase-9, and caspase-3 significantly increased, protein
      expression of Bcl-2 and Fas-L significantly decreased, and Fas protein expression
      was unchanged after SDT treatment. CONCLUSIONS: Our results suggested that the
      mitochondrial signal pathway may play a pivotal role in the apoptosis induced by
      SDT in C6 glioma cells.

PMID- 19597760
TI  - Intra-osseous ultrasound for pedicle screw positioning in the subaxial cervical
      spine: an experimental study.
AB  - BACKGROUND: In contrast to other regions of the human spine, dorsal fixation with
      rods and pedicle screws is comparatively rarely performed in the cervical spine.
      Although this technique provides a higher mechanical strength than the more
      frequently used lateral mass screws, many surgeons fear the relatively high rate
      of misplacements. This higher incidence is mainly due to the complex vertebral
      anatomy in this spinal segment. For correct screw placement, the availability of
      an immediate and efficient intra-operative imaging tool to ascertain the accuracy
      of the pedicle screw hole position would be beneficial. We have previously
      investigated the usefulness of an intraspinal, specifically, intra-osseous
      ultrasound technique in the lumbar spine. In this study its accuracy as a means
      of controlling intrapedicular screw hole positioning has been evaluated in the
      cervical spine. METHODS: An endovascular ultrasound transducer was used for the
      intra-luminal scanning of 54 pedicle screw holes in cadaveric human spine
      specimens. Twenty-three of these had been intentionally misplaced (cortex
      breached). The resulting image files were assessed by three investigators blinded
      to both the procedure and the corresponding CT findings. FINDINGS: The
      investigators differentiated correctly between adequately and poorly placed
      pedicle screw holes in 96% of cases. False negatives and false positives both
      occurred in no more than 1.8% of cases. CONCLUSIONS: Intrapedicular
      ultrasonography of pedicle screw holes in the cervical spine is a promising
      technique for the intra-operative assessment of bore hole placement and may
      increase operative safety and postoperative outcome in posterior cervical fusion
      surgery.

PMID- 19597761
TI  - Assessment of endocrine abnormalities in severe traumatic brain injury: a
      prospective study.
AB  - OBJECTIVE: The frequency and pattern of endocrine abnormalities among patients
      with traumatic brain injury have been the subject matter of very few studies.
      This study was intended to assess the pattern of endocrine dysfunction following
      severe head injury. METHODS: Severe head injury patients admitted to the
      Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi,
      from January to December in 1 year formed the study group. Apart from clinical
      assessment, NCCT of the head was performed on all patients on admission. A
      complete anterior pituitary hormone analysis was performed within 24 h of injury
      and was repeated at 2 weeks, 3 months and 6 months amongst patients who survived.
      RESULTS: A total of 99 patients were included in the study. Forty of our patients
      succumbed in the hospital. Rest of the patients were followed up for 6 months.
      Elevations of cortisol followed by prolactin were the most common hormonal
      derangements at admission. Midline shift on CT scans was inversely related to
      cortisol elevation and directly related to GH elevation. Infarct on CT scans was
      inversely related to cortisol and LH elevation. A significant alteration was
      found in the decreasing trend of the mean T4 values and normalisation or a
      decreasing trend from initially elevated mean cortisol and GH levels during
      follow-up (p < 0.05). CONCLUSIONS: This study reveals that abnormalities in
      hormonal profiles appear to be relatively common in severe traumatic brain injury
      and fluctuate significantly over at least 6 months; there is a correlation with
      age and radiological findings. Performance of hormonal analysis evaluation should
      be considered in patients with severe brain injury so that appropriate hormonal
      replacement can be done to optimise the clinical outcome.

PMID- 19597762
TI  - Development of chronic encapsulated intracerebral hematoma after radiosurgery for
      a cerebral arteriovenous malformation.
AB  - BACKGROUND: We report a rare case of chronic encapsulated intracerebral hematoma
      (CEIH) after radiosurgery for a cerebral arteriovenous malformation (AVM).
      METHODS: Seven years after radiosurgery, magnetic resonance imaging revealed a
      high-intensity mass in the right basal ganglia with a peripheral low signal ring
      and fluid level on both T1- and T2-weighted images, which was compatible with
      CEIH. RESULTS: Stereotactic evacuation and placement of an Ommaya reservoir were
      performed. CONCLUSION: The concentration of vascular endothelial growth factor
      was high in the hematoma, suggesting that CEIH may be similar to chronic subdural
      hematoma.

PMID- 19597763
TI  - Creutzfeldt-Jakob disease with E200K PRNP mutation: a case report and revision of
      the literature.
AB  - Creutzfeldt-Jakob disease (CJD) is typically characterized by rapidly progressive
      dementia and myoclonus, and it is caused by a conformational change of the prion
      protein. The heritable forms are associated with mutation in the gene encoding
      the prion protein (PRNP). We report a 63-year-old Italian woman harboring the
      E200K PRNP mutation. Electroencephalogram, cerebrospinal fluid analysis, PRNP
      gene sequencing, histopathologic examination, immunohistochemical studies, and
      Western blotting analysis confirmed the diagnosis of CJD. Pyramidal involvement
      was the first sign and the prominent clinical feature. Later on, she developed
      also myoclonus, ataxia, spastic tetraplegia, and at last dementia with akinetic
      mutism. Usually, signs of degeneration of the pyramidal tracts occur in a small
      number of patients as the disease advances. Our report supports the variability
      of the clinical expression of the E200K genetic CJD. Further studies are needed
      to understand the molecular basis underlying the phenotypic variability among
      patients carrying this mutation.

PMID- 19597765
TI  - Extracellular recombinant protein production from Escherichia coli.
AB  - Escherichia coli is the most commonly used host for recombinant protein
      production and metabolic engineering. Extracellular production of enzymes and
      proteins is advantageous as it could greatly reduce the complexity of a
      bioprocess and improve product quality. Extracellular production of proteins is
      necessary for metabolic engineering applications in which substrates are polymers
      such as lignocelluloses or xenobiotics since adequate uptake of these substrates
      is often an issue. The dogma that E. coli secretes no protein has been challenged
      by the recognition of both its natural ability to secrete protein in common
      laboratory strains and increased ability to secrete proteins in engineered cells.
      The very existence of this review dedicated to extracellular production is a
      testimony for outstanding achievements made collectively by the community in this
      regard. Four strategies have emerged to engineer E. coli cells to secrete
      recombinant proteins. In some cases, impressive secretion levels, several grams
      per liter, were reached. This secretion level is on par with other eukaryotic
      expression systems. Amid the optimism, it is important to recognize that
      significant challenges remain, especially when considering the success cannot be
      predicted a priori and involves much trials and errors. This review provides an
      overview of recent developments in engineering E. coli for extracellular
      production of recombinant proteins and an analysis of pros and cons of each
      strategy.

PMID- 19597764
TI  - The evolution, complex structures and function of septin proteins.
AB  - The septin family is a conserved GTP-binding protein family and was originally
      discovered through genetic screening for budding yeast mutants. Septins are
      implicated in many cellular processes in fungi and metazoa. The function of
      septins usually depends on septin assembling into oligomeric complexes and highly
      ordered polymers. The expansion of the septin gene number in vertebrates
      increased the complex diversity of septins. In this review, we first discuss the
      evolution, structures and assembly of septin proteins in yeast and metazoa. Then,
      we review the function of septin proteins in cytokinesis, membrane remodeling and
      compartmentalization.

PMID- 19597766
TI  - Catheter thrombosis and percutaneous coronary intervention: fundamental
      perspectives on blood, artificial surfaces and antithrombotic drugs.
AB  - Recent reports of catheter thrombosis among patients undergoing percutaneous
      coronary intervention (PCI) have had a significant impact on the development of
      new antithrombotic therapies. The overall incidence of this complication is
      unknown, mainly because of underreporting in contemporary clinical trials of
      coronary intervention. The etiology and pathophysiology of catheter thrombosis is
      also poorly understood. Introduction of a catheter or guidewire may not provoke
      the intense thrombotic response that follows angioplasty or stenting, but factors
      such as catheter materials and device size, equipment surface properties, flow
      conditions, procedural time and complexity, as well as the antiplatelet and
      anticoagulant drugs administered during the procedure influence the likelihood,
      rate and clinical impact of thrombosis. The crucial role of cellular interactions
      involving tissue-factor bearing cells and platelets in the process of thrombosis
      also needs to be critically explored when considering blood contact with an
      exogenous material. Focusing on the inherently prothrombotic environment of
      percutaneous coronary intervention, we review the physiologic underpinnings of
      catheter and guidewire thrombosis, and explore the effect of antithrombotic drugs
      at the interface between blood and material surfaces. We also propose a clinical
      classification for the diagnosis and investigation of catheter thrombosis in
      clinical trials of anticoagulant therapy and PCI.

PMID- 19597767
TI  - Avian influenza virus A/chicken/Hubei/489/2004 (H5N1) induces caspase-dependent
      apoptosis in a cell-specific manner.
AB  - The economic damage caused by H5N1 avian influenza virus outbreak in domestic
      poultry and the threat of this virus to human health make the research of this
      virus highly significant. During the 2004 outbreak of avian influenza in Hubei
      province, People's Republic of China, we isolated a new H5N1 subtype avian
      influenza virus named as A/chicken/Hubei/489/2004(H5N1) (shorten as AIVHubei489
      here). In this study, the infectivity and apoptosis-inducing characteristics of
      AIVHubei489 were studied. We demonstrated that AIVHubei489 could infect MDCK
      cells and the infection induced apoptosis. Our data also showed that the
      apoptosis induced by this virus in MDCK cells was caspase activity dependent.
      Moreover, we proved that caspase 8 but not caspase 9 was involved in this
      apoptosis. The infectivity and apoptosis-inducing activity of AIVHubei489 in Vero
      and HeLa cells were also studied. Our results showed that AIVHubei489 could
      replicate in Vero and HeLa cells, but the infection did not cause apoptosis in
      either of the two cell lines. Thus, AIVHubei489 induced apoptosis through a
      caspase-dependent pathway in a cell-specific manner.

PMID- 19597768
TI  - [Perioperative myocardial damage in patients undergoing non-cardiac surgery. More
      questions than answers?].

PMID- 19597769
TI  - [Fibre optic-assisted endotracheal intubation through the laryngeal mask in
      children].
AB  - Fibre optic-assisted tracheal intubation through the laryngeal mask airway is a
      simple and safe procedure for securing the airway in the paediatric patient with
      unexpected and known difficult tracheal intubation. Therefore, fibre optic
      assisted tracheal intubation through the laryngeal mask airway represents a
      standard airway technique and must be part of clinical education and also regular
      training. However, the removal of the laryngeal mask airway over the tracheal
      tube is impaired by the short length of the tracheal tube, easily resulting in
      tube dislocation from the trachea. Among several techniques to overcome this
      problem, the Cook airway exchange catheter offers a reliable method not only for
      safe removal of the laryngeal mask over the tracheal tube but also for insertion
      of an adequate tracheal tube, particularly in paediatric patients. This is
      particularly important for cuffed tubes as the pilot balloon of the cuffed tube
      is too large to pass through laryngeal mask airway tubes size 2.5 and smaller.
      This presentation demonstrates fibre optic-assisted tracheal intubation through
      the laryngeal mask airway in children step-by-step and discusses its clinical
      implications. A list with compatible sizes of laryngeal mask airways, tracheal
      tubes and airway exchange catheters is also provided.

PMID- 19597770
TI  - [Randomized clinical trials in trauma surgery: decision-making in an area of
      conflict between eminence and evidence].
AB  - Well-designed, prospective, multicenter, randomized clinical trials (RCTs) define
      the gold standard of evidence-based medicine. The results of such trials
      represent the most solid rationale for therapeutic recommendations in the S3
      guideline of medical societies (http://www.leitlinie.de). The performance of
      studies according to good clinical practice (GCP) guidelines (Guidelines of the
      International Conference on Harmonization on Good Clinical Practice) is extremely
      demanding. The findings can shake long established principles and practices to
      the core. For more than 20 years now, the management of femoral shaft fractures
      in critically injured patients has been controversially discussed. There are two
      different concepts competing against each other: Early total care (ETC) aiming at
      definitive care by immediate femoral nailing and damage control orthopedics
      (DCO), where nailing is performed at a later time point after initial retention
      by the use of external fixation. In order to answer this still unresolved
      question, the Damage Control Study is currently under way involving 25 trauma
      centers throughout Germany. This study is funded by the Deutsche
      Forschungsgemeinschaft (DFG, German Research Association), it is endorsed by the
      board of Deutschen Gesellschaft fur Unfallchirurgie (DGU, German Society for
      Casualty Surgery) and it is embedded in a joint program of the DFG and the
      Federal Ministry of Education and Research (BMBF) to support clinical studies in
      Germany. Moreover, the study is supported by the ChirNet Site at Witten/Herdecke
      Koln (http://www.chir-net.de). Without a doubt, this RCT is one of the most
      important studies carried out in the field of care for the critically injured
      patient, because the results will have a profound influence on the future
      management of femoral shaft fractures in multiple trauma patients and because
      successful completion of this study will underline the high scientific competence
      and skills claimed by German trauma surgeons. At the same time, ironically, the
      success of this study is endangered by the dilemma of an as yet insufficient
      recruitment of suitable patients to be enrolled into the trial. In this article
      possible explanations for this problem will be discussed based on a case report
      and the specific challenges in performing RCTs that scrutinize questions in the
      field of surgery will be analyzed.

PMID- 19597771
TI  - [Treatment results of pertrochanteric and subtrochanteric femoral fractures: a
      retrospective comparison of PFN and PFNA].
AB  - BACKGROUND: Can the helical blade in proximal femur nailing antirotation (PFNA)
      reach a better bony fixation than proximal femur nailing (PFN), thereby
      decreasing complication rates and improving clinical outcomes especially in
      osteoporotic bone? MATERIALS AND METHODS: In a retrospective study complications
      and clinical treatment results of pertrochanteric and subtrochanteric femoral
      fractures were analyzed. For this purpose a group of patients stabilized with PFN
      (n=65) were compared to a patient group treated with PFNA (n=66). Objective and
      subjective parameters were acquired and analyzed by clinical follow-up studies
      using the Merle d'Aubigne score and X-ray evaluation. Individual bone quality was
      analyzed radiologically by determining the Singh index. The mean follow-up time
      was 7 months in each group. RESULTS: The PFNA showed a decrease in postoperative
      implant-associated complications especially in osteoporotic bone and unstable
      fracture types. CONCLUSION: The philosophy of the PFNA blade with better fixation
      through an increased implant-bone-interface and smaller cross-section, compaction
      of cancellous bone as well as an antirotational fixation, seems to show
      advantages compared to the double screw system of the PFN.

PMID- 19597772
TI  - [The challenge of auditing by medical health insurance inspectors: development of
      individual case inspections according to 275ff SGB V].
AB  - BACKGROUND: The German DRG (diagnosis-related groups) system has changed since
      the inauguration in 2005, whereby written inquiries and on-site auditing have
      been carried out by the medical inspection service for health insurance companies
      (MDK). Modifications in the G-DRG system are reflected in changes in the MDK
      visitations. This article describes exactly how these examinations have changed
      over time. In order to achieve this all auditing reports were evaluated. RESULTS:
      In the beginning correct coding and documentation were the most interesting items
      for the health insurance fund inspectors. Nowadays, length of in-patient
      treatment and specific points relating to current changes in the G-DRG system are
      being questioned. All areas of the hospital have now been examined during this
      period. There was no change in the loss resulting from the regular examinations
      over the years. However, the effort and input of manpower are extremely high.
      CONCLUSIONS: To cope with the changes in the German DRG system hospitals have to
      be flexible. The experiences with the regular MDK visitations can positively
      influence hospital organizational structures.

PMID- 19597773
TI  - [Volar locking compression plating versus dorsal plating for fractures of the
      distal radius: a prospective, randomized study].
AB  - INTRODUCTION: This study investigated the radiographic and functional outcomes of
      two different methods for treating fractures of the distal part of the radius.
      PATIENTS AND METHODS: In a prospective controlled study patients with forearm
      fractures were randomized by age, handedness, and fracture type. RESULTS: The
      study included 120 patients, with a mean age of 66 years. Forty-nine percent of
      the fractures were extraarticular, and 51% were intraarticular. In the group
      treated with volar locking compression plates, six patients needed operative
      decompression of the median nerve and one needed reconstruction of the extensor
      pollicis longus (EPL) tendon. The group with dorsal plating had three
      complications requiring operative treatment: one deep infection, one dislocation
      of the plate, and one reconstruction of the EPL tendon. The radiological results
      for the Stewart 1 score showed 68% excellent results in volar locking compression
      plating compared with 57% in dorsal plating. Regarding functional outcome, 48%
      with volar plating showed excellent results compared with 22% with dorsal
      plating, as measured by the Stewart 2 score. CONCLUSION: Despite significant
      advantages of the volar locked compression plating, subjective satisfaction did
      not differ between the two groups.

PMID- 19597774
TI  - Characterization and identification of gastric hyperplastic polyps and adenomas
      by confocal laser endomicroscopy.
AB  - BACKGROUND: Management of gastric polyps depends on their histologic composition.
      A real-time in vivo histologic diagnosis would be valuable to an "on table"
      management decision. Confocal laser endomicroscopy (CLE), a new diagnostic tool,
      allows real-time in vivo histologic evaluations of gastrointestinal lesions. This
      study aimed to assess the feasibility and practicability of using CLE to identify
      and differentiate gastric hyperplastic polyps and adenomas. METHODS: A total of
      66 patients with previously diagnosed polyps were recruited for this study
      between January 2007 and August 2008 at Qilu Hospital, Shandong University,
      China. The CLE imaging of hyperplastic polyps and adenomas was performed, and the
      CLE diagnosis was compared with the gold standard of histopathologic diagnosis.
      RESULTS: Imaging by CLE was successfully performed for 60 lesions of gastric
      hyperplastic polyps and 27 lesions of gastric adenomas. Compared with the
      surrounding background mucosa, gastric hyperplastic polyps and adenomas showed
      typical distinct appearances, respectively, by CLE. The overall accuracy of the
      in vivo CLE diagnosis of gastric hyperplastic polyps and adenomas during ongoing
      endoscopy was 90% (95% confidence interval [CI], 83-96%), and the overall
      accuracy of differentiating gastric hyperplastic polyps and adenomas by CLE was
      97% (95% CI, 90-99%) after endoscopy. Intraobserver agreement was perfect (kappa
      = 0.92; 95% CI, 0.82-0.99), and interobserver agreement was also good (kappa =
      0.83, 95% CI, 0.70-0.96). CONCLUSIONS: This study characterized confocal images
      of gastric hyperplastic polyps and adenomas as well as the high accuracy of
      differentiating hyperplastic polyps and adenomas using CLE.

PMID- 19597777
TI  - Mining protein-protein interactions from published literature using Linguamatics
      I2E.
AB  - Natural language processing (NLP) technology can be used to rapidly extract
      protein-protein interactions from large collections of published literature. In
      this chapter we will work through a case study using MEDLINE biomedical abstracts
      (1) to find how a specific set of 50 genes interact with each other. We will show
      what steps are required to achieve this using the I2E software from Linguamatics
      ( www.linguamatics.com (2)).To extract protein networks from the literature,
      there are two typical strategies. The first is to find pairs of proteins which
      are mentioned together in the same context, for example, the same sentence, with
      the assumption that textual proximity implies biological association. The second
      approach is to use precise linguistic patterns based on NLP to find specific
      relationships between proteins. This can reveal the direction of the relationship
      and its nature such as "phosphorylation" or "upregulation". The I2E system uses a
      flexible text-mining approach, supporting both of these strategies, as well as
      hybrid strategies which fall between the two. In this chapter we show how
      multiple strategies can be combined to obtain high-quality results.

PMID- 19597775
TI  - Effectiveness of a team participation training course for laparoscopy-assisted
      gastrectomy.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for stomach cancer is
      increasingly performed in Japan and Korea. However, the procedure still is
      considered to be complicated, and the optimal education system for trainees has
      not been established to date. METHODS: The authors organized a 1-day professional
      training course termed the LADG Basic Lab Course for LADG beginners. The
      participants were required to apply as a team of two surgeons and two operating
      nurses. The training course consisted of lectures and a live porcine lab
      emphasizing use of the ultrasonically activated device and the flexible
      laparoscope as well as team cooperation. The quality and effectiveness of the
      course were evaluated 6-10 months (mean, 8.2 +/- 2.2 months) after the course
      using a survey form sent to a representative surgeon of each institution.
      RESULTS: From May 2007 to July 2008, a total of 80 colleagues (47 surgeons and 33
      nurses) from 20 different centers in Japan participated in the training course.
      These surgeons represented 12.4 +/- 6.2 postgraduate years of education and had
      performed 2.7 +/- 4.9 LADGs before taking the course. In the follow-up
      evaluation, 12 institutions (60%) completed the survey forms. The mean operation
      time was reduced for eight respondents (66.7%). The number of LADGs performed per
      month increased in 50% of the respondents' institutions. The degree of lymph node
      dissection in LADG was extended for 66.7% of the respondents. The respondents
      answered that 100% of the first operators showed improvement in skills, as did
      59.5% of the scope operators and 59.5% of the nurses. CONCLUSIONS: The training
      course was an effective means of introducing LADG to each institution. Training
      courses emphasizing explanations of key devices and teamwork may be effective for
      the introduction of advanced laparoscopic surgeries.

PMID- 19597776
TI  - Factors associated with the long-term outcome of a self-expandable colon stent
      used for palliation of malignant colorectal obstruction.
AB  - BACKGROUND: The placement of self-expanding metal stents (SEMS) is a safe and
      effective definitive procedure for the palliation of malignant colorectal
      obstruction. In this study, the clinical outcomes, including the technical and
      clinical success rates, and the risk factors associated with the long-term
      outcomes of palliative SEMS were evaluated. METHODS: From February 2002 to April
      2008, 39 patients (18 men and 21 women) with malignant colorectal obstruction
      underwent placement of uncovered or covered stents under fluoroscopic or
      endoscopic guidance. The mean age of the patients was 64.5 +/- 14.6 years (range,
      37-96 years). RESULTS: The technical success rate was 100% (39/39), and the
      clinical success rate was 87.2% (34/39). Five cases had failed relief of the
      obstruction due to the development of migration in two patients, two
      malfunctions, and one perforation. Four patients experienced late complications:
      migration managed with a palliative colostomy in two patients, tumor ingrowth
      managed successfully with a second stent in one patient, perforation with an
      intraabdominal abscess at the upper margin of the stent 4 months after stenting
      in one patient. The location of the obstruction and the length of the stent were
      significant factors associated with a good outcome. Shorter stents (<10 cm) had
      better outcomes than longer stents (>or=10 cm; p = 0.008), and patients with a
      distal colorectal obstruction had better outcomes than those with a proximal
      colorectal obstruction (p = 0.015). CONCLUSION: Patients with bowel obstruction
      involving a short segment and those with a distal obstruction had better stent
      outcomes.

PMID- 19597778
TI  - Relative avidity, specificity, and sensitivity of transcription factor-DNA
      binding in genome-scale experiments.
AB  - One of the most crucial problems with genome-wide experimental analysis is how to
      extract meaningful biological phenomena from the resulting large data sets. Here,
      we present modeling and prediction techniques that are applied to genome-wide
      identification of in vivo protein-DNA binding sites from ChIP-based data sets. We
      develop a simple mixture probabilistic model of occurrence of non-specific and
      specific TF-DNA binding events for transcription factor binding to any site in
      the genome. We calculated the statistical significance of specific and non
      specific random binding events using Kolmogorov-Waring and exponential functions,
      respectively. The binding events in the chromosome regions associated with non
      specific, non-random binding loci were also identified and filtered out. The
      mixture model fits equally well to five different TFs (ERE, CREB, STAT1, Nanog,
      Oct4) data provided by ChIP-PET, SACO, and ChIP-Seq methods included in this
      study. We present a uniform methodology for estimating specificity, total number
      of binding sites, and sensitivity of data sets detected by these ChIP-based
      genome-wide experimental systems. We demonstrate strong heterogeneity of specific
      TF-DNA binding sites in terms of their avidity and by correlation between
      observed relative binding avidity of specific TF-DNA binding site and the level
      of mRNA transcription of the nearest gene target. Finally, we conclude that the
      sensitivity problem has not been resolved by current ChIP-based methods,
      including ChIP-Seq.

PMID- 19597779
TI  - Curation of inhibitor-target data: process and impact on pathway analysis.
AB  - The past decade has seen a significant emergence in the availability and use of
      pathway analysis tools. The workflow that is supported by most of the pathway
      analysis tools is limited to either of the following: a. a network of genes based
      on the input data set, or b. the resultant network filtered down by a few
      criteria such as (but not limited to) i. disease association of the genes in the
      network; ii. targets known to be the target of one or more launched drugs; iii.
      targets known to be the target of one or more compounds in clinical trials; and
      iv. targets reasonably known to be potential candidate or clinical biomarkers.
      Almost all the tools in use today are biased towards the biological side and
      contain little, if any, information on the chemical inhibitors associated with
      the components of a given biological network. The limitation resides as follows:
      The fact that the number of inhibitors that have been published or patented is
      probably several fold (probably greater than 10-fold) more than the number of
      published protein-protein interactions. Curation of such data is both expensive
      and time consuming and could impact ROI significantly. The non-standardization
      associated with protein and gene names makes mapping reasonably non
      straightforward. The number of patented and published inhibitors across target
      classes increases by over a million per year. Therefore, keeping the databases
      current becomes a monumental problem. Modifications required in the product
      architectures to accommodate chemistry-related content. GVK Bio has, over the
      past 7 years, curated the compound-target data that is necessary for the addition
      of such compound-centric workflows. This chapter focuses on identification,
      curation and utility of such data.

PMID- 19597780
TI  - Profiling protein interaction networks with functional protein microarrays.
AB  - The word protein is derived from the Greek "prota" meaning "of primary
      importance", a designation which appropriately acknowledges the central role
      proteins play in biological systems. Following translation and folding into a
      remarkable array of three-dimensional structures, individual proteins achieve
      added complexity and functionality through the addition of modifications
      including glycosylation, acetylation, methylation, and phosphorylation. This
      complexity is further expanded through the non-covalent interactions that occur
      between proteins, and it is these interactions that form the foundation for many
      of the exquisitely regulated cellular processes essential to life. As a result,
      protein-protein interactions comprise an important class of targets for drug
      discovery, and modulation of protein-protein binding represents an emerging
      therapeutic paradigm. Protein microarrays are an important tool to identify and
      characterize protein interactions, providing the ability to rapidly develop
      binding profiles between thousands of proteins in a simple multiplex assay. These
      assays are highly reproducible, sensitive, and scalable and provide an enabling
      technology for proteomic research within the rubric of systems biology.

PMID- 19597781
TI  - Manual annotation of protein interactions.
AB  - Protein interactions are the basic building blocks for assembly of pathways and
      networks. Almost any biologically meaningful functionality (for instance, linear
      signaling pathways, chains of metabolic reactions, transcription factor dimmers,
      protein complexes of transcriptosome, gene-disease associations) can be
      represented as a combination of binary relationships between "network objects"
      (genes, proteins, RNA species, bioactive compounds). Naturally, the assembled
      pathways and networks are only as good as their "weakest" link (i.e., a wrongly
      assigned interaction), and the errors multiply in multi-step pathways. Therefore,
      the utility of "systems biology" is fundamentally dependent on quality and
      relevance of protein interactions. The second important parameter is the sheer
      number of interactions assembled in the database. One needs a "critical mass" of
      species-specific interactions in order to build cohesive networks for a gene
      list, not a constellation of non-connected proteins and protein pairs. The third
      issue is semantic consistency between interactions of different types. Transient
      physical signal transduction interactions, reactions of endogenous metabolism,
      transcription factor-promoter binding, and kinetic drug-target interactions are
      all very different in nature. Yet, they have to fit well into one database format
      and be consistent in order to be useful in reconstruction of cellular
      processes.High-quality protein interactions are available in peer-reviewed "small
      experiment" literature and, to a much smaller extent, patents. However, it is
      very challenging to find the interactions, annotate with searchable (and
      computable) parameters, catalogue in the database format in computer readable
      form, and assemble into a database. There are hundreds of thousands of mammalian
      interactions scattered in tens of thousands of papers in a few thousands of
      scientific journals. There are no widely used standards for reporting the
      interactions in scientific texts and, therefore, text-mining tools have only
      limited applicability. In order to generate a meaningful database of protein
      interactions, one needs a well-developed technology of manual curation, equipped
      with computational solutions, managerial procedures, quality control, and users'
      feedback. Here we describe our ever-evolving annotation approach, the important
      annotation issues and our solutions, and the mammalian protein interactions
      database MetaBase which we have been working on for over 8 years.

PMID- 19597782
TI  - Gene set enrichment analysis.
AB  - Set enrichment analytical methods have become commonplace tools applied to the
      analysis and interpretation of biological data. The statistical techniques are
      used to identify categorical biases within lists of genes, proteins, or
      metabolites. The goal is to discover the shared functions or properties of the
      biological items represented within the lists. Application of these methods can
      provide great biological insight, including the discovery of participation in the
      same biological activity or pathway, shared interacting genes or regulators,
      common cellular compartmentalization, or association with disease. The methods
      require ordered or unordered lists of biological items as input, understanding of
      the reference set from which the lists were selected, categorical classifiers
      describing the items, and a statistical algorithm to assess bias of each
      classifier. Due to the complexity of most algorithms and the number of
      calculations performed, computer software is almost always used for execution of
      the algorithm, as well as for presentation of the results. This chapter will
      provide an overview of the statistical methods used to perform an enrichment
      analysis. Guidelines for assembly of the requisite information will be presented,
      with a focus on careful definition of the sets used by the statistical
      algorithms. The need for multiple test correction when working with large
      libraries of classifiers is emphasized, and we outline several options for
      performing the corrections. Finally, interpreting the results of such analysis
      will be discussed along with examples of recent research utilizing the
      techniques.

PMID- 19597783
TI  - PANTHER pathway: an ontology-based pathway database coupled with data analysis
      tools.
AB  - The availability of whole genome sequences from various model organisms and
      increasing experimental data and literatures stimulated the evolution of a
      systems approach for biological research. The development of computational tools
      and algorithms to study biological pathway networks has made great progress in
      helping analyze research data. Pathway databases become an integral part of such
      an approach. This chapter first discusses how biological knowledge is
      represented, particularly the importance of ontologies or standards in systems
      biology research. Next, we use PANTHER Pathway as an example to illustrate how
      ontologies and standards play a role in data modeling, data entry, and data
      display. Last, we describe the usage of such systems. We also describe the
      computational tools that utilize PANTHER Pathway information to analyze gene
      expression experimental data.

PMID- 19597784
TI  - Prioritizing genes for pathway impact using network analysis.
AB  - Prioritization, or ranking, of gene lists is becoming increasingly important for
      analyzing data generated from high-throughput assays like expression profiling
      and RNAi-based screening. This is especially the case when specific genes in a
      list need to be further validated using low-throughput experiments. In addition
      to gene set overlap enrichment methods, a complementary approach is to examine
      molecular interaction networks. These can provide putative functional insights
      based on gene connectivity, especially when many genes contain little or no
      annotation. For bench and computational biologists alike, using networks requires
      an informed selection of interaction data for network construction and strategies
      for managing network complexity. Moreover, graph theory and social network
      analysis methods can be used to isolate critical subnetworks and quantify network
      properties. Here, I discuss the basic components of networks, implications of
      their structure for functional interpretation, and common metrics used for
      prioritization. Although this is still an ongoing area of research, networks are
      providing new ways for gauging pathway impact in large-scale data sets.

PMID- 19597785
TI  - Discovering biological networks from diverse functional genomic data.
AB  - Recent advances in biotechnology have produced a wealth of genomic data, which
      capture a variety of complementary cellular features. While these data promise to
      yield key insights into molecular biology, much of the available information
      remains underutilized because of the lack of scalable approaches for integrating
      signals across large, diverse data sets. A proper framework for capturing these
      numerous snapshots of complementary phenomena under a variety of conditions can
      provide the holistic view necessary for developing precise systems-level
      hypotheses. Here we describe bioPIXIE, a system for combining information from
      diverse genomic data sets to predict biological networks. bioPIXIE utilizes a
      Bayesian framework for probabilistic integration of several high-throughput
      genomic data types including gene expression, protein-protein interactions,
      genetic interactions, protein localization, and sequence data to predict
      biological networks. The main purpose of the system is to support user-driven
      exploration through the inferred functional network, which is enabled by a
      public, web-based interface. We describe the features and supporting methods of
      this integration and discovery framework and present case examples where bioPIXIE
      has been used to generate specific, testable hypotheses for Saccharomyces
      cerevisiae, many of which have been confirmed experimentally.

PMID- 19597786
TI  - Functional analysis of OMICs data and small molecule compounds in an integrated
      "knowledge-based" platform.
AB  - Analysis of microarray, SNPs, proteomics, and other high-throughput (OMICs) data
      is challenging because of its biological complexity and high level of technical
      and biological noise. One way to deal with both problems is to perform analysis
      with a high-fidelity annotated knowledge base of protein interactions, pathways,
      and functional ontologies. This knowledge base has to be structured in a computer
      readable format and must include software tools for managing experimental data,
      analysis, and reporting. Here we present MetaDiscovery, an integrated platform
      for functional data analysis which is being developed at GeneGo for the past 8
      years. On the content side, MetaDiscovery encompasses a comprehensive database of
      protein interactions of different types, pathways, network models and 10
      functional ontologies covering human, mouse, and rat proteins. The analytical
      toolkit includes tools for gene/protein list enrichment analysis, statistical
      "interactome" tool for identification of over- and under-connected proteins in
      the data set, and a network module made up of network generation algorithms and
      filters. The suite also features MetaSearch, an application for combinatorial
      search of the database content, as well as a Java-based tool called MapEditor for
      drawing and editing custom pathway maps. Applications of MetaDiscovery include
      identification of potential biomarkers and drug targets, pathway hypothesis
      generation, analysis of biological effects for novel small molecule compounds,
      and clinical applications (analysis of large cohorts of patients and
      translational and personalized medicine).

PMID- 19597787
TI  - Kinetic modeling as a tool to integrate multilevel dynamic experimental data.
AB  - The metabolic networks are the most well-studied biochemical systems, with an
      abundance of in vitro and in vivo data available for quantitative estimation of
      its kinetic parameters. In this chapter, we present our approach to developing
      mathematical description of metabolic pathways. The model-based integration of
      reaction kinetics and the utilization of different types of experimental data
      including temporal dependencies have been described in detail. Software package
      DBSolve7 which allows us to develop kinetic model of the biochemical system and
      integrate experimental data has been presented.

PMID- 19597789
TI  - Semantic data integration and knowledge management to represent biological
      network associations.
AB  - The vast quantities of information generated by academic and industrial research
      groups are reflected in a rapidly growing body of scientific literature and
      exponentially expanding resources of formalized data including experimental data
      from "-omics" platforms, phenotype information, and clinical data. For
      bioinformatics, several challenges remain: to structure this information as
      biological networks enabling scientists to identify relevant information; to
      integrate this information as specific "knowledge bases"; and to formalize this
      knowledge across multiple scientific domains to facilitate hypothesis generation
      and validation and, thus, the generation of new knowledge. Risk management in
      drug discovery and clinical research is used as a typical example to illustrate
      this approach. In this chapter we will introduce techniques and concepts (such as
      ontologies, semantic objects, typed relationships, contexts, graphs, and
      information layers) that are used to represent complex biomedical networks. The
      BioXM Knowledge Management Environment is used as an example to demonstrate how a
      domain such as oncology is represented and how this representation is utilized
      for research.

PMID- 19597788
TI  - Cytoscape: a community-based framework for network modeling.
AB  - Cytoscape is a general network visualization, data integration, and analysis
      software package. Its development and use has been focused on the modeling
      requirements of systems biology, though it has been used in other fields.
      Cytoscape's flexibility has encouraged many users to adopt it and adapt it to
      their own research by using the plugin framework offered to specialize data
      analysis, data integration, or visualization. Plugins represent collections of
      community-contributed functionality and can be used to dynamically extend
      Cytoscape functionality. This community of users and developers has worked
      together since Cytoscape's initial release to improve the basic project through
      contributions to the core code and public offerings of plugin modules. This
      chapter discusses what Cytoscape does, why it was developed, and the extensions
      numerous groups have made available to the public. It also describes the
      development of a plugin used to investigate a particular research question in
      systems biology and walks through an example analysis using Cytoscape.

PMID- 19597790
TI  - Solutions for complex, multi data type and multi tool analysis: principles and
      applications of using workflow and pipelining methods.
AB  - Analytical workflow technology, sometimes also called data pipelining, is the
      fundamental component that provides the scalable analytical middleware that can
      be used to enable the rapid building and deployment of an analytical application.
      Analytical workflows enable researchers, analysts and informaticians to integrate
      and access data and tools from structured and non-structured data sources so that
      analytics can bridge different silos of information; compose multiple analytical
      methods and data transformations without coding; rapidly develop applications and
      solutions by visually constructing analytical workflows that are easy to revise
      should the requirements change; access domain-specific extensions for specific
      projects or areas, for example, text extraction, visualisation, reporting,
      genetics, cheminformatics, bioinformatics and patient-based analytics;
      automatically deploy workflows directly into web portals and as web services to
      be part of a service-oriented architecture (SOA). By performing workflow
      building, using a middleware layer for data integration, it is a relatively
      simple exercise to visually design an analytical process for data analysis and
      then publish this as a service to a web browser. All this is encapsulated into
      what can be referred to as an 'Embedded Analytics' methodology which will be
      described here with examples covering different scientifically focused data
      analysis problems.

PMID- 19597791
TI  - High-throughput siRNA screening as a method of perturbation of biological systems
      and identification of targeted pathways coupled with compound screening.
AB  - High-throughput RNA interference (HT-RNAi) is a powerful research tool for
      parallel, 'genome-wide', targeted knockdown of specific gene products. Such
      perturbation of gene product expression allows for the systematic query of gene
      function. The phenotypic results can be monitored by assaying for specific
      alterations in molecular and cellular endpoints, such as promoter activation,
      cell proliferation and survival. RNAi profiling may also be coupled with drug
      screening to identify molecular correlates of drug response. As with other
      genomic-scale data, methods of data analysis are required to handle the unique
      aspects of data normalization and statistical processing. In addition, novel
      techniques or knowledge-mining strategies are required to extract useful
      biological information from HT-RNAi data. Knowledge-mining strategies involve the
      novel application of bioinformatic tools and expert curation to provide
      biological context to genomic-scale data such as that generated from HT-RNAi
      data. Pathway-based tools, whether text-mining based or manually curated, serve
      an essential role in knowledge mining. These tools can be applied during all
      steps of HT-RNAi screen experiments including pre-screen knowledge gathering,
      assay development and hit confirmation and validation. Most importantly, pathway
      tools allow the interrogation of HT-RNAi data to identify and prioritize pathway
      based biological information as a result of specific loss of gene function.

PMID- 19597792
TI  - Pathway and network analysis with high-density allelic association data.
AB  - Network and pathway analysis tools are traditionally used to interrogate gene
      expression data in order to understand the biological processes affected by a
      particular manipulation or disease/condition of interest. A systems-level
      understanding of the biological processes affected in particular disease states
      can allow one to identify candidates not only for pharmaceutical intervention but
      also for potential prognostic and diagnostic markers for the disease. However,
      network and pathway analyses are currently underutilized in the interpretation of
      large-scale genetic association study results. While simple monogenic, overtly
      Mendelian diseases are easily understood in the context of a single genetic
      aberration, the vast majority of diseases follow more complex patterns of
      inheritance and are influenced by a large number of genes and environmental
      stimuli. Genetic association studies investigating complex diseases that exploit
      network and pathway analysis tools can shed light on the genetic networks
      affected by particular genetic variations and sequence polymorphisms, just as
      gene expression studies can reveal genes dysregulated in a particular disease
      state. In this chapter, we describe the steps required to undertake network
      analysis of large-scale genetic association data - in particular single
      nucleotide polymorphism (SNP)-based genetic association data - in terms of data
      organization/preparation, SNP weighting schemes, and pathway analysis methods. We
      provide two illustrative examples that demonstrate the application of this
      approach: one involving the analysis of cancer tumor resequencing studies and
      another involving a genome-wide association study (GWAS).

PMID- 19597793
TI  - miRNAs: from biogenesis to networks.
AB  - In eukaryotes, besides alternative splicing and promoter regulation of
      "classical" genes, there is also another level of genetic regulation based on non
      coding RNAs (ncRNAs). The most famous group of ncRNAs is microRNAs, probably the
      biggest number of genome regulators. Here, we summarize the knowledge that has
      been accumulated about the microRNA field, focusing our attention on brief
      history, biogenesis, regulated mechanism, computational methods of miRNA finding
      and miRNA target sites, miRNAs and diseases, and miRNAs and network analysis.

PMID- 19597794
TI  - MetaMiner (CF): a disease-oriented bioinformatics analysis environment.
AB  - MetaMiner (CF) is a data analysis platform for a broad range of CF researchers
      including wet lab biologists, bioinformaticians, clinicians, and chemists. To
      understand disease mechanisms and gain insight into complex biological actions,
      analysis of even simple gene interactions often requires integration of a variety
      of separate data resources such as literature, 3D molecular models, metabolic
      pathways, ontologies, small molecules, and drugs. Large-scale data sets from high
      throughput screening assays, microarrays, and other data intensive procedures
      present an even greater challenge in data handling and analysis which now
      requires interdisciplinary teams of scientists with strikingly diverse
      backgrounds including computer scientists, statisticians, biologists, and
      clinicians. To address the issues raised by the complexity of analysis and
      resource limitations of many research laboratories, MetaMiner (CF) was developed
      by GeneGo under direction and funding of Cystic Fibrosis Foundation Therapeutics.
      The platform was designed to provide the CF community with a single tool for
      analyzing experimental data in a disease-centered environment. To that end, the
      most important biological and chemical experimental data available today in
      cystic fibrosis research have been assembled and integrated with data analysis
      and visualization tools to highlight the key pathways leading to and perturbed by
      the disease. GeneGo developers assembled and edited CF-specific content and
      designed the disease-specific interface under the guidance and review of a team
      of leading cystic fibrosis experts. Updates and revisions will be processed
      quarterly under the direction of the CF Foundation Therapeutics.

PMID- 19597795
TI  - Translational research and biomedical informatics.
AB  - A critical need exists to address real issues that appear when a physician is
      faced with a patient and the need to make clinical decisions that will impact the
      patient, their quality life, and those of the patient's family. Bridging this gap
      between the clinical need and the available technologies, clinical data, and
      clinician input is the role that Biomedical Informatics can play in driving the
      evolution of patient care in the post-genome era.

PMID- 19597796
TI  - ArrayTrack: an FDA and public genomic tool.
AB  - A robust bioinformatics capability is widely acknowledged as central to realizing
      the promises of toxicogenomics. Successful application of toxicogenomic
      approaches, such as DNA microarrays, inextricably relies on appropriate data
      management, the ability to extract knowledge from massive amounts of data, and
      the availability of functional information for data interpretation. At the FDA's
      National Center for Toxicological Research (NCTR), we are developing a public
      microarray data management and analysis software, called ArrayTrack, that is also
      used in the routine review of genomic data submitted to the FDA. ArrayTrack
      stores a full range of information related to DNA microarrays and clinical and
      non-clinical studies as well as the digested data derived from proteomics and
      metabonomics experiments. In addition, ArrayTrack provides a rich collection of
      functional information about genes, proteins, and pathways drawn from various
      public biological databases for facilitating data interpretation. Many data
      analysis and visualization tools are available with ArrayTrack for individual
      platform data analysis, multiple omics data integration, and integrated analysis
      of omics data with study data. Importantly, gene expression data, functional
      information, and analysis methods are fully integrated so that the data analysis
      and interpretation process is simplified and enhanced. Using ArrayTrack, users
      can select an analysis method from the ArrayTrack tool box, apply the method to
      selected microarray data, and the analysis of results can be directly linked to
      individual gene, pathway, and Gene Ontology analysis. ArrayTrack is publicly
      available online (
      http://www.fda.gov/nctr/science/centers/toxicoinformatics/ArrayTrack/index.htm )
      and the prospective user can also request a local installation version by
      contacting the authors.

PMID- 19597797
TI  - [Autism and autistic disorders. Historical and current aspects].
AB  - Since its first use in medical literature the meaning of the term autism has
      constantly changed. An historical overview indicates that in both adult and child
      psychiatry autism was first used to refer to a symptom of schizophrenia. Later on
      the use of the term in child psychiatry took a different independent course,
      which led to present-day conceptualization of autism, mainly due to the work of
      Leo Kanner and Hans Asperger. Currently autism and autistic disorders are
      regarded as severe developmental disorders and, due to their stable nature, have
      gained considerable attention in adult psychiatry. In order to better understand
      this development, the path from onset to reception is traced via Kanner and
      Asperger. In the search for central characteristics of autism, one finds
      restrictions in social communication and interaction, which can be explained by
      fundamental deficits in social cognition. These restrictions in social cognition
      can be considered the central characteristic of autism - one which has been a
      constant since the phenomenon was first described. Our historical review
      considers to what extent experimental psychopathological research can deepen our
      understanding of the disorder.

PMID- 19597798
TI  - Impact of depth of pedigree and inclusion of historical data on the estimation of
      additive variance and breeding values in a sugarcane breeding program.
AB  - Sugarcane breeders in Australia combine data across four selection programs to
      obtain estimates of breeding value for parents. When these data are combined with
      full pedigree information back to founding parents, computing limitations mean it
      is not possible to obtain information on all parents. Family data from one
      sugarcane selection program were analysed using two different genetic models to
      investigate how different depths of pedigree and amount of data affect the
      reliability of estimating breeding value of sugarcane parents. These were the
      parental and animal models. Additive variance components and breeding values
      estimated from different amounts of information were compared for both models.
      The accuracy of estimating additive variance components and breeding values
      improved as more pedigree information and historical data were included in
      analyses. However, adding years of data had a much larger effect on the
      estimation of variance components of the population, and breeding values of the
      parents. To accurately estimate breeding values of all sugarcane parents, a
      minimum of three generations of pedigree and 5 years of historical data were
      required, while more information (four generations of pedigree and 7 years of
      historical data) was required when identifying top parents to be selected for
      future cross pollination.

PMID- 19597799
TI  - Does diabetes therapy influence the risk of cancer?

PMID- 19597800
TI  - Nitrative stress and poly(ADP-ribose) polymerase activation in healthy and
      gestational diabetic pregnancies.
AB  - AIMS/HYPOTHESIS: Increased oxidative-nitrosative stress, poly(ADP-ribose)
      polymerase (PARP) activation and subsequent cellular damage play important roles
      in the complications of both diabetes mellitus and pregnancy. Our aim was to
      investigate nitrative stress and PARP activity levels during normal and
      gestational diabetic (GDM) pregnancy in both maternal and fetal tissues. METHODS:
      Blood samples were collected during pregnancy (weeks 16-29 and 36-40), and
      placental and umbilical cord tissues were harvested after delivery from healthy
      volunteers and GDM patients subjected to a carbohydrate-restricted diet or
      insulin treatment. Immunohistochemical staining was performed on leucocytes and
      tissue sections using anti-nitrotyrosine (NT), anti-poly(ADP-ribose) (PAR) and
      anti-apoptosis inducing factor antibodies. RESULTS: In healthy pregnancies the
      intensity of NT and PAR staining of leucocytes correlated positively with
      gestational week (R (2) = 0.43, p < 0.01 and R (2) = 0.49, p < 0.001,
      respectively). In patients on a carbohydrate-restricted diet PAR staining was
      already strong in weeks 16-29 (p < 0.001 vs control) and did not increase
      further. In weeks 16-29 there was a correlation between PAR staining and the 2 h
      value of the oral glucose tolerance test (R (2) = 0.49, p < 0.001). Patients with
      the highest level of leucocyte PARP activity later required insulin therapy,
      which decreased the intensity of NT and PAR staining. Placental and umbilical
      cord tissues also had a higher level of nitrative stress markers in GDM
      pregnancies, but the highest level of PARP activity was observed after insulin
      therapy. CONCLUSIONS/INTERPRETATION: Continuous elevation of tyrosine nitration
      and PARP activation may be considered physiological during pregnancy. However,
      the high level of PARP activity in early pregnancy may signal the subsequent
      development of severe GDM.

PMID- 19597802
TI  - Photonic sensor devices for explosive detection.
AB  - For the sensitive online and in situ detection of gaseous species, optical
      methods are ideally suited. In contrast to chemical analysis, no sample
      preparation is necessary and therefore spectroscopic methods should be favorable
      both in respect of a fast signal recovery and economically because no disposal is
      needed. However, spectroscopic methods are currently not widely used for security
      applications. We review photonic sensor devices for the detection of explosives
      in the gas phase as well as the condensed phase and the underlying spectroscopic
      techniques with respect to their adaptability for security applications, where
      high sensitivity, high selectivity, and a low false-alarm rate are of importance.
      The measurements have to be performed under ambient conditions and often remote
      handling or even operation in standoff configuration is needed. For handheld and
      portable equipment, special attention is focused on the miniaturization and
      examples for already-available sensor devices are given.

PMID- 19597803
TI  - Passive standoff detection of RDX residues on metal surfaces via infrared
      hyperspectral imaging.
AB  - Hyperspectral images of galvanized steel plates, each containing a stain of
      cyclotrimethylenetrinitramine (RDX), were recorded using a commercial long-wave
      infrared imaging spectrometer. Demonstrations of passive RDX chemical detection
      at areal dosages between 16 and 90 microg/cm(2) were carried out over practical
      standoff ranges between 14 and 50 m. Anomaly and target detection algorithms were
      applied to the images to determine the effect of areal dosage and sensing
      distance on detection performance for target RDX. The anomaly detection
      algorithms included principal component analysis, maximum autocorrelation
      factors, and principal autocorrelation factors. Maximum difference factors and
      principal difference factors are novel multivariate edge detection techniques
      that were examined for their utility in detection of the RDX stains in the
      images. A target detection algorithm based on generalized least squares was
      applied to the images, as well, to see if the algorithm can identify the compound
      in the stains on the plates using laboratory reflection spectra of RDX,
      cyclotetramethylenetetranitramine (HMX), and 2,4,6-trinitrotoluene (TNT) as the
      target spectra. The algorithm could easily distinguish between the nitroaromatic
      (TNT) compound and the nitramine (RDX, HMX) compounds, and, though the
      distinction between RDX and HMX was less clear, the mean weighted residuals
      identified RDX as the stain on the plate. Improvements that can be made in this
      detection technique are discussed in detail. As expected, it was found that
      detection was best for short distances and higher areal dosages. However, the
      target was easily detected at all distances and areal dosages used in this study.

PMID- 19597801
TI  - Psychotropic drug-induced locomotor hyperactivity and prepulse inhibition
      regulation in male and female aromatase knockout (ArKO) mice: role of dopamine D1
      and D2 receptors and dopamine transporters.
AB  - RATIONALE AND OBJECTIVES: The aim of the present study was to investigate the
      possible role of oestrogen in schizophrenia by comparing aromatase knockout
      (ArKO) mice, which are unable to produce oestrogen, with wild-type controls using
      two behavioural animal models with relevance to the illness, psychotropic drug
      induced locomotor hyperactivity and prepulse inhibition (PPI). RESULTS: Baseline
      PPI was not different between ArKO and controls. Treatment with apomorphine, MK
      801 and amphetamine caused disruption of PPI in all groups. However, in female
      but not male ArKO mice, the effect of both apomorphine and amphetamine was
      reduced. In female ArKO mice, amphetamine-induced hyperlocomotion was markedly
      reduced, but in male mice, the genotype difference was far smaller. Female but
      not male ArKO mice also showed a reduction of phencyclidine-induced locomotor
      hyperactivity. The density of dopamine transporters, but not D1 and D2 receptors,
      was significantly increased in the caudate putamen of male but not female ArKO
      mice compared to wild-type mice. This could represent a compensatory dopaminergic
      upregulation in male ArKO mice. CONCLUSION: Because of their lack of oestrogen
      production, it was anticipated that ArKO mice would display enhanced effects of
      amphetamine on locomotor activity and PPI. Instead, in these animals, aromatase
      knockout appeared to be 'protective'. This may represent limitations in the
      ability to model a complex illness such as schizophrenia in a constitutive
      knockout model, such as ArKO mice. Moreover, the current results may point at the
      involvement of other sex steroids, which are also altered in ArKO mice, in
      dopaminergic control of behaviour.

PMID- 19597804
TI  - Auditory dominance over vision in the perception of interval duration.
AB  - The "ventriloquist effect" refers to the fact that vision usually dominates
      hearing in spatial localization, and this has been shown to be consistent with
      optimal integration of visual and auditory signals (Alais and Burr in Curr Biol
      14(3):257-262, 2004). For temporal localization, however, auditory stimuli often
      "capture" visual stimuli, in what has become known as "temporal ventriloquism".
      We examined this quantitatively using a bisection task, confirming that sound
      does tend to dominate the perceived timing of audio-visual stimuli. The dominance
      was predicted qualitatively by considering the better temporal localization of
      audition, but the quantitative fit was less than perfect, with more weight being
      given to audition than predicted from thresholds. As predicted by optimal cue
      combination, the temporal localization of audio-visual stimuli was better than
      for either sense alone.

PMID- 19597805
TI  - Antidepressants and cardiovascular outcomes in patients without known
      cardiovascular risk.
AB  - PURPOSE: To identify a cohort of subjects without treatment for any
      cardiovascular risk and analyze the potential causative role of treatment for
      depression on the development of major cardiovascular outcomes during 2 years of
      follow-up. METHODS: We carried out a record-linkage analysis of hospital
      discharge records, prescription databases and vital statistics for all
      consecutive patients aged 30 years or older in one Italian region during a 4-year
      period. Depression was defined in terms of exposure to at least three
      prescriptions of antidepressant drugs within 1 year. Patients had no history of
      treatment with cardiovascular or antidiabetic agents and had not been
      hospitalized with a diagnosis of any cardiovascular condition in the preceding
      year. Follow-up was extended up to 2 years or to time to occurrence of major
      outcomes defined as either all-cause mortality, hospitalization for any
      cardiovascular cause or chronic exposure to cardiovascular drugs
      (antihypertensive, statins, antidiabetics). The results are expressed hazard
      ratios (HRs) and 95% confidence intervals (CIs) within age categories (30-49, 50
      59, > or = 60 years). RESULTS: A total of 105,573 persons without treated
      cardiovascular risk at baseline were identified, among whom 1,129 (1.1%) had been
      chronically exposed to antidepressant treatment. Treated depression determined an
      increased risk of all cause-mortality (HR 1.88, 95% CI 1.33-2.66, p < 0.001) and
      of subsequent treatment with antidiabetic agents (HR 0.89, 95% CI 1.34-2.66, p <
      0.001), statins (HR 1.87, 95% CI 1.53-2.29, p < 0.001) and antihypertensive drugs
      (HR 1.25, 95% CI 1.07-1.47, p = 0.006). CONCLUSION: Among the general population
      without treated cardiovascular risk, pharmacologic treatment for depression was
      associated with an increase in all-cause mortality and major cardiovascular
      outcomes.

PMID- 19597806
TI  - Prognostic value of the quality indicator "concurrent use of three or more
      psychotropic drugs" among residents of long-term-care facilities.

PMID- 19597807
TI  - Comparison of two different running models for the shock wave lithotripsy machine
      in Taipei City Hospital: self-support versus outsourcing cooperation.
AB  - To compare two different running models including self-support and outsourcing
      cooperation for the extracorporeal shock wave lithotripsy (SWL) machine in Taipei
      City Hospital, we made a retrospective study. Self-support means that the
      hospital has to buy an SWL machine and get all the payment from SWL. In
      outsourcing cooperation, the cooperative company provides an SWL machine and
      shares the payment with the hospital. Between January 2002 and December 2006, we
      used self-support for the SWL machine, and from January 2007 to December 2008, we
      used outsourcing cooperation. We used the method of full costing to calculate the
      cost of SWL, and the break-even point was the lowest number of treatment sessions
      of SWL to make balance of payments every month. Quality parameters including
      stone-free rate, retreatment rate, additional procedures and complication rate
      were evaluated. When outsourcing cooperation was used, there were significantly
      more treatment sessions of SWL every month than when utilizing self-support (36.3
      +/- 5.1 vs. 48.1 +/- 8.4, P = 0.03). The cost of SWL for every treatment session
      was significantly higher using self-support than with outsourcing cooperation
      (25027.5 +/- 1789.8 NT$ vs. 21367.4 +/- 201.0 NT$). The break-even point was 28.3
      (treatment sessions) for self-support, and 28.4 for outsourcing cooperation, when
      the hospital got 40% of the payment, which would decrease if the percentage
      increased. No significant differences were noticed for stone-free rate,
      retreatment rate, additional procedures and complication rate of SWL between the
      two running models. Besides, outsourcing cooperation had lower cost (every
      treatment session), but a greater number of treatment sessions of SWL every month
      than self-support.

PMID- 19597808
TI  - Pediatric littoral cell angioma of the spleen: multimodality imaging including
      diffusion-weighted imaging.
AB  - Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating
      from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in
      children. We present the US, CT, and MRI findings including diffusion-weighted
      imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous
      studies on liver lesions have shown that DWI allows differentiation of vascular
      tumors from primary neoplasms and metastatic disease. The current case indicates
      that increased ADC values within the splenic lesions suggest a vascular etiology,
      which might help narrow the differential diagnosis.

PMID- 19597809
TI  - Identification of natural killer cell receptor clusters in the platypus genome
      reveals an expansion of C-type lectin genes.
AB  - Natural killer (NK) cell receptors belong to two unrelated, but functionally
      analogous gene families: the immunoglobulin superfamily, situated in the
      leukocyte receptor complex (LRC) and the C-type lectin superfamily, located in
      the natural killer complex (NKC). Here, we describe the largest NK receptor gene
      expansion seen to date. We identified 213 putative C-type lectin NK receptor
      homologs in the genome of the platypus. Many have arisen as the result of a
      lineage-specific expansion. Orthologs of OLR1, CD69, KLRE, CLEC12B, and CLEC16p
      genes were also identified. The NKC is split into at least two regions of the
      genome: 34 genes map to chromosome 7, two map to a small autosome, and the
      remainder are unanchored in the current genome assembly. No NK receptor genes
      from the LRC were identified. The massive C-type lectin expansion and lack of Ig
      domain-containing NK receptors represents the most extreme polarization of NK
      receptors found to date. We have used this new data from platypus to trace the
      possible evolutionary history of the NK receptor clusters.

PMID- 19597810
TI  - The role of anaerobic digestion in controlling the release of tetracycline
      resistance genes and class 1 integrons from municipal wastewater treatment
      plants.
AB  - In this study, the abilities of two anaerobic digestion processes used for sewage
      sludge stabilization were compared for their ability to reduce the quantities of
      three genes that encode resistance to tetracycline (tet(A), tet(O), and tet(X))
      and one gene involved with integrons (intI1). A two-stage,
      thermophilic/mesophilic digestion process always resulted in significant
      decreases in the quantities of tet(X) and intI1, less frequently in decreases of
      tet(O), and no net decrease in tet(A). The thermophilic stage was primarily
      responsible for reducing the quantities of these genes, while the subsequent
      mesophilic stage sometimes caused a rebound in their quantities. In contrast, a
      conventional anaerobic digestion process rarely caused a significant decrease in
      the quantities of any of these genes, with significant increases occurring more
      frequently. Our results demonstrate that anaerobic thermophilic treatment was
      more efficient in reducing quantities of genes associated with the spread of
      antibiotic resistance compared to mesophilic digestion.

PMID- 19597811
TI  - Characterization of novel thermostable dextranase from Thermotoga lettingae TMO.
AB  - Biochemical properties of a putative thermostable dextranase gene from Thermotoga
      lettingae TMO were determined in a recombinant protein (TLDex) expressed in
      Escherichia coli and purified to sevenfold apparent homogeneity. The 64-kDa
      protein displayed maximum activity at pH 4.3, and enzyme activity was stable from
      pH 4.3-10. The optimal temperature was 55-60 degrees C during 15 min incubation,
      and the half-life of the enzyme was 1.5 h at 65 degrees C. The enzyme showed
      higher activity against alpha-(1 --> 6) glucan and released isomaltose and
      isomaltotriose as main products from dextran T2000. An unusual kinetic feature of
      TLDex was the negative cooperative behavior on the reaction of dextran T2000
      cleavage. Enzyme activity was not significantly affected by the presence of metal
      ions, except for the strong inhibited by 1 mM Fe(2+) and Ag(2+). TLDex may prove
      useful as an enzyme for high temperature sugar milling processes.

PMID- 19597812
TI  - Purification and characterization of a multienzyme complex produced by
      Paenibacillus curdlanolyticus B-6.
AB  - Paenibacillus curdlanolyticus B-6 showed effective degradation activities for
      xylan and cellulose and produced an extracellular multienzyme complex
      (approximately 1,450 kDa) containing several xylanases and cellulases. To
      characterize the multienzyme complex, we purified the complex from culture
      supernatants by four kind of chromatography. The purified multienzyme complex was
      composed of a 280-kDa protein with xylanase activity, a 260-kDa protein that was
      a truncated form on the C-terminal side of the 280-kDa protein, two xylanases of
      40 and 48 kDa, and 60 and 65 kDa proteins having both xylanase and carboxymethyl
      cellulase activities. The 280-kDa protein resembled the scaffolding proteins of
      cellulosomes based on its migratory behavior in polyacrylamide gels and as a
      glycoprotein. Cloning of the 40-kDa major xylanase subunit named Xyn11A revealed
      that Xyn11A contained two functional domains which belonged to glycosyl hydrolase
      family-11 and to carbohydrate-binding module family-36, respectively, and a
      glycine- and asparagine-rich linker. However, an amino acid sequence similar to a
      dockerin domain, which is crucial to cellulosome assembly, was not found in
      Xyn11A. These results suggest that the multienzyme complex produced by P.
      curdlanolyticus B-6 should assemble by a mechanism distinct from the cohesin
      dockerin interactions known in cellulosomes.

PMID- 19597813
TI  - D-lactic acid production from cellooligosaccharides and beta-glucan using L-LDH
      gene-deficient and endoglucanase-secreting Lactobacillus plantarum.
AB  - In order to achieve direct fermentation of an optically pure D: -lactic acid from
      cellulosic materials, an endoglucanase from a Clostridium thermocellum (CelA)
      secreting plasmid was introduced into an L: -lactate dehydrogenase gene (ldhL1)
      deficient Lactobacillus plantarum (ldhL1) bacterial strain. CelA expression and
      its degradation of beta-glucan was confirmed by western blot analysis and enzyme
      assay, respectively. Although the CelA-secreting ldhL1 assimilated
      cellooligosaccharides up to cellohexaose (although not cellotetraose), the main
      end product was acetic acid, not lactic acid, due to the conversion of lactic
      acid to acetic acid. Cultivation under anaerobic conditions partially suppressed
      this conversion resulting in the production of 1.27 g/l of D: -lactic acid with a
      high optical purity of 99.5% from a medium containing 2 g/l of cellohexaose.
      Subsequently, D: -lactic acid fermentation from barley beta-glucan was carried
      out with the addition of Aspergillus aculeatus beta-glucosidase produced by
      recombinant Aspergillus oryzae and 1.47 g/l of D: -lactic was produced with a
      high optical purity of 99.7%. This is the first report of direct lactic acid
      fermentation from beta-glucan and a cellooligosaccharide that is a more highly
      polymerized sugar than cellotriose.

PMID- 19597814
TI  - Regulation of hydantoin-hydrolyzing enzyme expression in Agrobacterium
      tumefaciens strain RU-AE01.
AB  - Optically pure D-: amino acids, like D-: hydroxyphenylglycine, are used in the
      semi-synthetic production of pharmaceuticals. They are synthesized industrially
      via the biocatalytic hydrolysis of p-hydroxyphenylhydantoin using enzymes derived
      from Agrobacterium tumefaciens strains. The reaction proceeds via a three-step
      pathway: (a) the ring-opening cleavage of the hydantoin ring by a D-:
      hydantoinase (encoded by hyuH), (b) conversion of the resultant D-: N
      carbamylamino acid to the corresponding amino acid by a D-: N-carbamoylase
      (encoded by hyuC), and (c) chemical or enzymatic racemization of the un-reacted
      hydantoin substrate. While the structure and biochemical properties of these
      enzymes are well understood, little is known about their origin, their function,
      and their regulation in the native host. We investigated the mechanisms involved
      in the regulation of expression of the hydantoinase and N-carbamoylase enzyme
      activity in A. tumefaciens strain RU-AE01. We present evidence for a complex
      regulatory network that responds to the growth status of the cells, the presence
      of inducer, and nitrogen catabolite repression. Deletion analysis and site
      directed mutagenesis were used to identify regulatory elements involved in
      transcriptional regulation of hyuH and hyuC expression. Finally, a comparison
      between the hyu gene clusters in several Agrobacterium strains provides insight
      into the function of D-: selective hydantoin-hydrolyzing enzyme systems in
      Agrobacterium species.

PMID- 19597815
TI  - Influence of inoculum density on population dynamics and dauer juvenile yields in
      liquid culture of biocontrol nematodes Steinernema carpocapsae and S. feltiae
      (Nematoda: Rhabditida).
AB  - For improvement of mass production of the rhabditid biocontrol nematodes
      Steinernema carpocapsae and Steinernema feltiae in monoxenic liquid culture with
      their bacterial symbionts Xenorhabdus nematophila and Xenorhabdus bovienii,
      respectively, the effect of the initial nematode inoculum density on population
      development and final concentration of dauer juveniles (DJs) was investigated.
      Symbiotic bacterial cultures are pre-incubated for 1 day prior to inoculation of
      DJs. DJs are developmentally arrested and recover development as a reaction to
      food signals provided by their symbionts. After development to adults, the
      nematodes produce DJ offspring. Inoculum density ranged from 1 to 10 x 10(3) DJ
      per milliliter for S. carpocapsae and 1 to 8 x 10(3) DJs per milliliter for S.
      feltiae. No significant influence of the inoculum density on the final DJ yields
      in both nematode species was recorded, except for S. carpocapsae cultures with a
      parental female density <2 x 10(3) DJs per milliliter, in which the yields
      increased with increasing inoculation density. A strong negative response of the
      parental female fecundity to increasing DJ inoculum densities was recorded for
      both species with a maximum offspring number per female of >300 for S.
      carpocapsae and almost 200 for S. feltiae. The compensative adaptation of
      fecundity to nematode population density is responsible for the lack of an
      inoculum (or parental female) density effect on DJ yields. At optimal inoculation
      density of S. carpocapsae, offspring were produced by the parental female
      population, whereas S. feltiae always developed a F1 female population, which
      contributed to the DJ yields and was the reason for a more scattered distribution
      of the yields. The F1 female generation was accompanied by a second peak in X.
      bovienii density. The optimal DJ inoculum density for S. carpocapsae is 3-6 x
      10(3) DJs per milliliter in order to obtain >10(3) parental females per
      milliliter. Density-dependent effects were neither observed on the DJ recovery
      nor on the sex ratio in the parental adult generation. As recovery varied between
      different batches, assessment of the recovery of inoculum DJ batches is
      recommended. S. feltiae was less variable in DJ recovery usually reaching >90%.
      The recommended DJ inoculum density is >5 x 10(3) DJs per milliliter to reach >2
      x 10(3) parental females per milliliter. The mean yield recorded for S.
      carpocapsae was 135 x 10(3) and 105 x 10(3) per mililiter for S. feltiae.

PMID- 19597817
TI  - Cutaneous myeloma and bortezomib.

PMID- 19597816
TI  - Somatostatin receptor scintigraphy might be useful for detecting skeleton
      abnormalities in patients with multiple myeloma and plasmacytoma.
AB  - PURPOSE: Somatostatin receptor expression has been demonstrated on a number of
      plasma cell lines. Therefore, we questioned whether somatostatin receptor
      scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM)
      activity. METHODS: SRS was performed in newly diagnosed (n = 9) or relapsing (n =
      18) MM patients or in patients with localized plasmacytoma (n = 2). The results
      were compared with radiographic findings. RESULTS: A positive SRS was
      demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed
      patients and in both patients with plasmacytoma. The SRS findings corresponded
      with radiographic abnormalities in 40% of the patients. However, in relapsed
      patients 60% demonstrated increased SRS uptake in areas without new radiographic
      abnormalities. The positive SRS corresponded with histologically proven disease
      activity and responded upon treatment. Moreover, immunohistochemical staining of
      MM material demonstrated concordant somatostatin receptor sst3 staining in five
      of six patients. CONCLUSION: These results demonstrate that SRS is a valuable
      tool to detect disease activity, especially in relapsing MM patients.

PMID- 19597818
TI  - Inclusion complexes of noscapine in beta-cyclodextrin offer better solubility and
      improved pharmacokinetics.
AB  - PURPOSE: Noscapine (NOS) is a unique class of tubulin-binding anticancer agents.
      Their potential usefulness as anticancer drugs is however limited by the poor
      bioavailability, thus necessitating administration of a higher dose regime in the
      range of 300-600 mg/kg for tumor growth inhibition. To augment bioavailability,
      we prepared an inclusion complex of NOS in beta-cyclodextrin (beta-CD) and
      evaluated its physico-chemical characteristics. METHOD AND RESULTS: Our phase
      solubility analysis shows a 1:1-complexation (Kc approximately 0.454 mM(-1)) of
      NOS with beta-CD that offers better dissolution properties. We confirmed complex
      formation in solid state by differential scanning calorimetry, powder X-ray
      diffractometry, Fourier-transform infrared spectroscopy, 1H nuclear magnetic
      resonance spectroscopy, rotating frame Overhauser enhancement spectroscopy and by
      molecular modeling methods. Based upon theoretical calculations in gas phase, we
      propose O-CH2-O- in orientation of NOS in the beta-CD cavity. The thermal
      behavior data also provides complementary evidences of complex formation. The
      pharmacokinetic studies showed a 1.87-fold increase in bioavailability of NOS
      upon complexation in the beta-CD inclusion complex state as compared to free NOS.
      Furthermore, the complex retains the anticancer attributes of NOS. CONCLUSION:
      Our studies propose for the first time a stable NOS-beta-CD inclusion complex as
      an effective approach to enhance the solubility and bioavailability of NOS for
      anticancer therapy.

PMID- 19597819
TI  - Bronchial diverticula in smokers on thin-section CT.
AB  - The objective was to determine the prevalence of bronchial diverticula in smokers
      on thin-section CT and the relationship to clinical and other morphological
      features on CT. Thin-section CT images of 503 cigarette smokers were assessed for
      the profusion and location of diverticula in the major airways. The extent of the
      bronchial diverticula was recorded as follows: grade 0, none; grade 1, one to
      three diverticula; grade 2, more than three diverticula. The extent of emphysema,
      bronchial wall thickness, clinical features, and pulmonary function were compared
      in the sub-groups stratified according to the extent of bronchial diverticula. A
      total of 229/503 (45.5%) smokers had bronchial diverticula, with 168/503 (33.3%)
      and 61/503 (12.2%) having grade 1 and 2 bronchial diverticula respectively.
      Subjects with grade 2 bronchial diverticula were heavier smokers, reported a
      history of coughing more frequently, and showed more severe functional
      impairment, greater extent of emphysema and more severe bronchial wall thickening
      compared with subjects with grade 1 and those individuals without bronchial
      diverticula (P < 0.05). Multivariate regression analysis revealed that only
      bronchial wall thickness predicted the extent of the bronchial diverticula (P <
      0.0001). Bronchial diverticula are a frequent finding in the major airways of
      smokers, and they are associated with other markers of smoking-related damage.

PMID- 19597821
TI  - Integrated teaching of anatomy and radiology using three-dimensional image post
      processing.
AB  - This article presents a new way of teaching by integrating both anatomy and
      radiology using three-dimensional image post-processing tools. One preclinical
      and one clinical module were developed for integrated teaching of anatomy and
      radiology. Potential benefits were assessed by anonymous evaluation among the 176
      participating students. The students highly appreciated the new approach,
      especially the high degree of interactivity with the post-processing software and
      the possibility to correlate the real dissection with the virtual dissection.
      Students agreed that three-dimensional imaging and postprocessing improved their
      understanding of difficult anatomical topics and topographical relations. We
      consider the new approach to provide great additional benefits for participating
      students regarding preparation for everyday clinical practice. In particular, it
      imparts familiarity with imaging and image post-processing techniques and may
      improve anatomical understanding, radiological diagnostic skills and three
      dimensional appreciation.

PMID- 19597822
TI  - The role of arterial stimulation and simultaneous venous sampling in addition to
      cross-sectional imaging for localisation of biochemically proven insulinoma.
AB  - Insulinomas, although rare, cause considerable morbidity but are frequently
      amenable to surgical cure. Laparoscopic surgery can now be considered if the
      tumour is localised pre-operatively, but the optimal imaging approach has not
      been determined. The objective of this study was to evaluate the ability of
      different imaging investigations, including CT, MRI, endoscopic ultrasound,
      octreotide scintigraphy and arterial stimulation with simultaneous venous
      sampling (ASVS), to localise insulinomas. All patients with biochemically proven
      insulinoma at our institution underwent ASVS along with other imaging
      investigations as part of their routine investigation. The results of these
      investigations were compared with histological findings. Twenty-eight patients
      with biochemically proven insulinoma confirmed by histology were identified.
      Ultimately ASVS localised a lesion in all patients. Seventeen patients (61%) had
      laparoscopic surgery. Tumor-detection rates for other imaging investigations
      included 43.5% of cases using CT, 71% using MRI, 86% using endoscopic ultrasound
      and 33% using octreotide scintigraphy. In four patients, the ASVS was the only
      test to correctly localise the lesion. ASVS should be considered routinely before
      surgery to ensure accurate localisation of insulinomas.

PMID- 19597820
TI  - "In-house" pharmacological management for computed tomography coronary
      angiography: heart rate reduction, timing and safety of different drugs used
      during patient preparation.
AB  - We retrospectively evaluated the effect, timing and safety of different
      pharmacological strategies during 64-slice CT coronary angiography (CT-CA). From
      the institutional database of CT-CAwe enrolled 560 consecutive patients with
      suspected coronary artery disease. The type of drug preparation (group 1 = no
      treatment; group 2 = oral metoprolol; group 3 = other; group 4 = intravenous (IV)
      atenolol; group 5 = IV atenolol + nitrates; NR = non-responders), timing, and
      adverse effects were recorded. Heart rate (HR) during different preparation
      phases was recorded. Four adverse effects were recorded, none of which was
      attributable to pharmacological treatment. In all groups, except group 1, the HR
      on arrival was significantly reduced by the pharmacological treatment (p<0.01).
      Group 4 showed the best (-16+/-8 bpm) HR reduction. There was no significant
      effect on HR due to nitrates (p = 0.49), while a slight increase due to contrast
      material was noted (p<0.05). Average time required for preparation was 44+/
      25min. Groups 4 and 5 showed the most effective timing (8+/-9 min and 8+/-8 min,
      respectively; p<0.01). Pharmacological preparation in patients undergoing CT-CA
      is safe and effective. Best results in terms of HR reduction and fast preparation
      are obtained with IV administration of beta-blockers.

PMID- 19597823
TI  - [Volume overload from hydrogel expander after treatment for enophthalmos].
AB  - In the subject of this case report, a self-inflating hydrogel expander was
      implanted as a treatment for posttraumatic enophthalmos in a fully sighted eye.
      The intervention caused hypertropia with diplopia, restriction of eye movements,
      visual field defects, and colour desaturation as a result of excessive swelling
      of the expander. Once the expander volume was adjusted, clinical signs regressed,
      and the aesthetic results were excellent. Following the implantation of self
      inflating orbit expanders, it is advisable to carry out immediate follow-up
      during the expander's swelling period, and long-term follow-up is also advised to
      rule out late sequelae, as a position-dependent secondary glaucoma could occur.

PMID- 19597824
TI  - [A stochastic test for validity control of visual acuity statements].
AB  - BACKGROUND: When a patient's statement of reduced visual acuity (VA) does not
      correspond to the ophthalmologic findings, the validity of the statement should
      be checked before intensive diagnostics are initiated, because the statement may
      be untrue or may overstate a factual reduction in VA. A primary question is
      whether the patient's statement differs from his or her true VA, and if so, by
      how much. Especially in examinations for medical opinion, individuals may be well
      informed on how to check the validity of VA statements. Thus, modifications of
      standard test strategies are required. We examined a new test that was designed
      to allow probabilistic evaluation. PATIENTS AND METHODS: The optotype board has
      the form of a poster measuring 150 cm in height and 125 cm in width. It contains
      16 lines corresponding to the logarithmic VA levels from 0.12 up to 4.0 at a
      distance of 5 m. Each line consists of nine Landolt-Cs with four alternative
      orientations. VA was determined by a 1/1 criterion for each single measurement at
      each of the nine optotype columns. In cases of low vision (VA <0.25), the test
      distance was reduced accordingly. The test was given to 100 patients (VA 0.012
      2.75), 20 healthy subjects (VA >1.0) who were requested to simulate a VA of 0.1,
      and 13 individuals who were examined for medical opinion, nine of whom were
      suspected (by results of other testing) of stating nonorganic visual
      deterioration. The mean and the individual distribution of the nine single values
      were analyzed and compared with the distribution within a typical psychometric
      function as determined by a Monte Carlo simulation on 100,000 single
      measurements. RESULTS: None of the 100 normally cooperative patients yielded more
      than seven idential single values, and only one yielded seven. The single values
      scattered by one to three lines. Of the 20 pseudomalingerers (examined at a
      distance of 2.5 m), in seven subjects (35%) we found an atypical pattern of
      single values (seven or nine identical values). VA results of those 10 subjects
      who could read the calibration column on the board (reference distance 5 m)
      scattered around 0.06. Results of those 10 subjects who were examined after the
      calibration column had been replaced with lower values (reduced by a factor of 4)
      scattered around 0.13. Of the nine individuals examined for medical opinion who
      were suspect of stating too low a VA, six (67%) showed an atypical distribution
      of single values. CONCLUSION: This convenient test is a practical tool both for
      regular determination of visual acuity and for detection of false statements by
      means of an atypical psychometric function. It also allows for application of
      further validity checks. Intentionally false statements can be influenced by
      misleading calibration values.

PMID- 19597825
TI  - pRb2/p130 protein in relation to clinicopathological and biological variables in
      rectal cancers with a clinical trial of preoperative radiotherapy.
AB  - BACKGROUND: pRb2/p130 plays a key role in cell proliferation and is a
      considerable progress about expression patterns of pRb2/p130 in number of
      malignancies. However, pRb2/p130 expression and its significance in rectal cancer
      remain unknown. The purpose of the present study was to investigate pRb2/p130
      protein patterns and their correlations with clinicopathological and biological
      factors in rectal cancer patients with or without preoperative radiotherapy (RT).
      PATIENT/METHODS: pRb2/p130 protein was examined by immunohistochemistry in 130
      primary tumors, along with the corresponding 61 distant normal mucosa specimens,
      85 adjacent normal mucosa specimens, 34 lymph node metastases, and 93 primary
      tumor biopsies from rectal cancer patients who participated in a Swedish clinical
      trial of preoperative RT. RESULTS: The pRb2/p130 protein was mainly localized in
      the cytoplasm of tumor cells. In nonradiated cases, the lack of pRb2/p130 was
      related to advanced tumor-node-metastases stage, poorer differentiation, weak
      fibrosis, less inflammatory infiltration, higher Ki-67, and positive Cox-2
      expression (p < 0.05). In radiated cases, the lack of pRb2/p130 was related to
      nonstaining of Cox-2 and survivin (p < 0.05). pRb2/p130 protein in primary tumors
      tended to be increased after RT (27% vs 16%, p = 0.07). CONCLUSION: pRb2/p130 was
      mainly localized in the cytoplasm rather than in the nucleus in rectal cancer.
      After RT, pRb2/p130 protein seems to be increased in primary tumors, and further
      the relationship of the pRb2/p130 with the clinicopathological and biological
      variables changed compared to the nonradiated cases. However, we did not find
      that the pRb2/p130 was directly related to RT, tumor recurrence, and patients'
      survival.

PMID- 19597826
TI  - Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using
      immunoproteomics analysis.
AB  - BACKGROUND AND AIMS: Sera from cancer patients contain tumor-specific
      autoantibodies directly against antigenic proteins. The identification of tumor
      autoantigens may have utility in cancer diagnosis, prognosis, and therapy. In
      this study, we used immunoproteomics analysis to identify tumor proteins that
      elicit humoral response in colorectal cancer (CRC). MATERIALS AND METHODS: The
      CRC cell line HCT116 was used as a source of proteins for two-dimensional
      polyacrylamide gel electrophoresis and subsequent Western blot analysis in which
      individual serum from patients with CRC was analyzed for autoantibodies. Proteins
      that specifically react with sera from cancer patients were identified by matrix
      assisted laser desorption ionization time-of-flight mass spectrometric analysis.
      In addition, the selected protein expression in tumor tissues collected from 40
      patients with CRC were assessed by immunohistochemistry. RESULTS: An autoantibody
      against inosine monophosphate dehydrogenase II (IMPDH2) identified by mass
      spectrometry was detected in eight out of 25 patients with CRC. However, none of
      the 15 healthy controls demonstrated autoantibody to IMPDH2.The expression of
      IMPDH2 in tumor tissue was significantly higher in patients with CRC than that in
      healthy subjects. CONCLUSIONS: The result confirmed that the immunoproteomics
      analysis holds considerable promise for the discovery of tumor-associated
      antigens. IMPDH2 may be a protein biomarker and novel therapeutic target in CRC.

PMID- 19597827
TI  - Oxidative stress damage and oxidative stress responses in the choroid plexus in
      Alzheimer's disease.
AB  - Choroid plexus homogenates from 27 cases with Alzheimer disease-related pathology
      (AD), stages I/0 (n = 5), III-IV/0-B (n = 15) and V-VI/B-C (n = 7) and 3 age
      matched controls (no clinical symptoms, no neuropathological lesions) were
      processed for gel electrophoresis and western blotting for oxidation markers
      carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL). Increased CEL and CML
      expression was seen in AD cases stages IVB, and V-VI/B-C when compared to
      controls and cases with AD-related pathology classified as I/0 and III/0.
      Variable stress damage was seen in stage III/B. Although lower stages of AD did
      not show beta-amyloid deposition in the choroid plexus, the amount of beta
      amyloid was very variable at stages V/VI as revealed by western blotting,
      suggesting that other factors in addition to local fibrillar beta-amyloid were
      associated with oxidative damage in the choroid plexus. Two-dimensional gel
      electrophoresis and western blotting to CEL and CML in combination with mass
      spectrometry disclosed increased intensity of variable spots in AD cases leading
      to the identification of tyrosine 3/tryptophan 5-monooxygenase activation
      protein, zeta polypeptide, tropomyosin 3 isoform, and apolipoprotein A-II (ApoA
      II) as targets of increased oxidative damage in AD. Oxidation of these proteins
      may result in impaired protein interactions, protein folding and protein kinase
      activity; abnormal function of endothelial and vascular smooth muscle cells; and
      impaired HDL-cholesterol metabolism in the choroid plexus in advanced stages of
      AD.

PMID- 19597828
TI  - Llama VHH antibody fragments against GFAP: better diffusion in fixed tissues than
      classical monoclonal antibodies.
AB  - Camelids produce antibodies made of homodimeric heavy chains, and the antigen
      binding region being composed of a single domain called VHH. These VHHs are much
      smaller than complete IgG. They are also more thermostable and more soluble in
      water; they should, therefore, diffuse more readily in the tissues. VHHs,
      expressed in bacteria, are easier to produce than conventional monoclonal
      antibodies. Because of these special characteristics, these antibody fragments
      could have interesting developments in immunohistochemistry and in the
      development of biomarkers. To test the possibility of their use in
      immunohistochemistry (IHC), we selected the glial fibrillary acidic protein
      (GFAP), a well-known marker of astrocytes. One alpaca (Lama pacos) was immunized
      against GFAP. Lymphocytes were isolated; the DNA was extracted; the VHH-coding
      sequences were selectively amplified. Three VHHs with a high affinity for GFAP
      and their corresponding mRNA were selected by ribosome display. Large quantities
      of the recombinant VHHs coupled with different tags were harvested from
      transfected bacteria. One of them was shown to immunolabel strongly and
      specifically to GFAP of human astrocytes in tissue sections. The quality of the
      IHC was comparable or, in some aspects, superior to the quality obtained with
      conventional IgG. The VHH was shown to diffuse on a longer distance than
      conventional monoclonal antibodies in fixed cortical tissue: a property that may
      be useful in immunolabeling of thick sections.

PMID- 19597830
TI  - Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with
      cumulative effect with epigallocatechin-3-gallate.
AB  - In skin inflammation, vascular endothelial growth factor (VEGF) and CXCL-8/IL-8
      play an important role and are produced by activated keratinocytes. Extracts from
      Ginkgo biloba leaves (GBE), widely used in phytotherapy, have been reported to
      exert antioxidant and anti-inflammatory properties in the skin. We therefore
      evaluated the effects of GBE on the release of VEGF and CXCL8/IL-8 by normal
      human keratinocytes (NHKs) activated by tumor necrosis factor alpha (TNFalpha).
      Moreover, as we previously showed that epigallocatechin-3-gallate (EGCG) reduces
      VEGF and CXCL8/IL-8 secretion in TNFalpha-activated NHKs, we also tested its
      effect in association with GBE. Our results showed that GBE exerted a potent
      inhibition on VEGF and CXCL8/IL-8 levels in activated cells. In association with
      EGCG, GBE down-regulated VEGF and CXCL8/IL-8 levels in a cumulative manner in
      TNFalpha-stimulated NHKs. These results suggest that GBE, alone or in association
      with EGCG may contribute to moderate inflammatory processes in skin diseases
      associated with angiogenesis.

PMID- 19597831
TI  - Malign mural nodules associated with serous ovarian tumor of borderline
      malignancy: a case report and literature review.
AB  - BACKGROUND: Cystic tumors of ovary, whether benign, borderline, or malignant may
      be associated with mural nodule of various types, including sarcomas, sarcoma
      like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous
      borderline ovarian tumor with mural nodules of mixed type are very rare. CASE: A
      54-year-old woman referred with abdominal swelling. Imaging studies revealed a
      huge mass localized in pelvis and lower abdomen and grade 1-2 left renal
      hydronephrosis. Preoperative Ca-125 was 798 U/ml. In exploratory laparotomy there
      was a 16 cm mass adherent to lateral abdominal wall and intestines. Adhesiolysis
      and de-bulking surgery were performed including bilateral pelvic, para-aortic
      lymphadenectomy, appendectomy and omentectomy. Left ureter was found to be
      dilated because of the infiltration of distal part by the tumor, so distal
      ureteral resection and neoureterocystostomy were performed. Final pathology
      revealed borderline serous ovarian tumor with mural nodules which were consisted
      of SLMNs, multiple and sharply demarcated from the adjacent tumor, and
      sarcomatous nodules showing infiltrative appearance in metastatic regions. Mural
      nodules showed a positive reaction for vimentin and SMA but were negative for
      cytokeratin and also necrosis, hemorrhage, and 10-15 mitoses in 10 high power
      fields were noted. She had postoperative chemotherapy and follow-up is going on
      without metastases in her first year. CONCLUSION: The existence of sarcomatous
      nodules combined with the SLMN necessitates a careful histologic analysis for
      treatment and the determination of prognosis. However, too few cases of mixed
      type mural nodules have been published to warrant a conclusion regarding their
      prognosis.

PMID- 19597832
TI  - Acute abdomen due to rupture of Sertoli cell tumor.
AB  - PURPOSE: To present a rare case of Sertoli cell tumor that presents with acute
      abdomen. CASE: A 28-year-old patient with symptoms of acute abdomen has presented
      to our emergency department. Her examinations revealed a 12 x 10 cm heterogeneous
      mass in the right ovarian fossa. Laparotomy was carried out immediately. Frozen
      pathological study revealed a low-grade sex-cord stromal cell tumor. Right
      salpingo-oopherectomy was performed. During 2 years of follow-up, there was no
      evidence of disease. CONCLUSION: Although rupture of a malignant ovarian tumor is
      an infrequent cause of acute abdomen, it should be considered in the differential
      diagnosis of acute abdomen.

PMID- 19597833
TI  - Restriction analysis of otosclerosis-associated CD46 splicing variants.
AB  - Otosclerosis is a primary bone remodeling disorder of the human otic capsule and
      is associated with persistent measles virus infection. The human cellular
      receptor of measles virus is the membrane cofactor protein (MCP, CD46), which has
      14 well-described splicing variants. Unique CD46 expression pattern of the otic
      capsule and the stapes footplate may determine the susceptibility for persistent
      measles virus infection. A total of 51 surgically removed ankylotic stapes
      footplates were analyzed by histopathological and molecular biological methods,
      respectively. Nucleic acids were extracted. Measles virus sequences were detected
      by nucleoprotein RNA-specific reverse transcriptase polymerase chain reaction (RT
      PCR). Alternatively spliced RNA of CD46 isoforms was amplified by RT-PCR; cDNA
      amplimers were separated by SDS poly-acrylamide gel electrophoresis and were
      purified from the gel. Complementary DNA of CD46 isoforms was restricted by
      endonuclease enzymes having CD46-specific recognition sites. The presence of
      viral RNA was associated exclusively with the histopathological diagnosis of
      otosclerosis; the stapes specimens with negative measles virus belonged to non
      otosclerotic stapes fixations. All specimens (N = 51) were characterized by the
      consecutive expression of five CD46 variants (c, d, e, f and one shorter
      unidentified isoform). Histologically confirmed ostosclerotic specimens (N = 21)
      were characterized by increased expression levels of variant "f" and the unknown
      isoform. Increased expression levels of these isoforms and special CD46
      expression pattern of the human otic capsule might produce modified or
      pathological intracellular signalization that could create the possibility of
      persistent measles virus infection.

PMID- 19597829
TI  - The ubiquitin proteasome system in neuropathology.
AB  - The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable
      cellular proteins. In the process of ubiquitination the small protein ubiquitin
      is attached to a target protein by a peptide bond. The ubiquitinated target
      protein is subsequently shuttled to a protease complex known as the 26S
      proteasome and subjected to degradative proteolysis. The UPS facilitates the
      turnover of proteins in several settings. It targets oxidized, mutant or
      misfolded proteins for general proteolytic destruction, and allows for the
      tightly controlled and specific destruction of proteins involved in development
      and differentiation, cell cycle progression, circadian rhythms, apoptosis, and
      other biological processes. In neuropathology, alteration of the UPS, or
      mutations in UPS target proteins may result in signaling abnormalities leading to
      the initiation or progression of tumors such as astrocytomas, hemangioblastomas,
      craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of
      the UPS may also contribute to tumor progression by perturbation of DNA
      replication and mitotic control mechanisms, leading to genomic instability. In
      neurodegenerative diseases caused by the expression of mutant proteins, the
      cellular accumulation of these proteins may overload the UPS, indirectly
      contributing to the disease process, e.g., sporadic Parkinsonism and prion
      diseases. In other cases, mutation of UPS components may directly cause
      pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and
      spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie
      cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and
      muscle and nerve diseases, e.g., inclusion body myopathy and giant axon
      neuropathy. This paper describes the basic biochemical mechanisms comprising the
      UPS and reviews both its theoretical and proven involvement in neuropathological
      diseases. The potential for the UPS as a target of pharmacological therapy is
      also discussed.

PMID- 19597834
TI  - The root and development of otorhinolaryngology in traditional Chinese medicine.
AB  - There is an increasing trend in society to look beyond conventional medicine to
      find answers to problems in health. Traditional Chinese medicine (TCM) is one of
      the most popular alternative, complementary therapies worldwide. It is becoming a
      popular alternative in otorhinolaryngology where its use in the treatment of
      sinusitis, tinnitus, deafness and Meniere's disease is growing. Despite the
      general awareness of TCM, the literature relating specifically to
      otorhinolaryngology is relatively scarce. In this review, we have traced the
      origin and development of otorhinolaryngology with respect to TCM and have
      provided a few interesting insights into otorhinolaryngology, as it used to be
      practised. Archaeological sources have shown that diseases affecting the ear,
      nose and throat were of medical concern as early as the 18th century BC. The
      first practising otorhinolaryngologist can be traced back to the 5th century BC.
      Acupuncture, moxibustion, herbal therapy and massage were amongst his treatments.
      Otorhinolaryngology was recognised as a major specialty when formal medical
      education began in the 7th century AD. Therapeutic measures since then expanded
      to include exercise, food therapy and surgery. References to using oesophageal
      speech as a substitute voice generator, the use of copper wire to excise nasal
      polyps, procedures for removal of sharp foreign bodies in the oropharynx, repair
      of lacerated trachea and treatment of cancer of lips can be found in historical
      notes. In conclusion, from its primitive roots, TCM has developed into a distinct
      branch of health care system in China today that works alongside Western
      medicine.

PMID- 19597835
TI  - Globus jugularis and dysphagia in patients with hiatus hernia.
AB  - The aim of the article was to study if there is any relationship between globus
      sensation in the jugular fossa (GJ), intermittent esophageal dysphagia (IED), and
      the presence of a hiatus hernia, and if GJ can be relieved after hiatus hernia
      repair. 167 patients with a hiatus hernia (Group A) and 61 other patients with
      hiatus hernia and gastroesophageal reflux disease who were surgically treated
      with Nissen fundoplication (Group B), filled in a symptom questionnaire on GJ and
      IED. GJ was found in 66% and IED in 68% of patients in group A. In group B, 49%
      had GJ and 64% IED before surgery. At surgical follow-up 16% (P < 0.005) and 43%
      (P < 0.05) had GJ and IED, respectively. The combination of GJ and IED was found
      in 28% of IED patients before operation and in 31% at surgical follow-up. The
      high frequency of GJ in patients with hiatus hernia and the significant relief of
      GJ after hiatus hernia repair imply that GJ most likely is a referred sensation
      from the esophagus. IED and GJ are two parallel phenomena in patients with hiatus
      hernia, but do not seem to have any causal relationship.

PMID- 19597836
TI  - An animal model for the analysis of cochlear blood flow [corrected] disturbance
      and hearing threshold in vivo.
AB  - Impairment of cochlear blood flow (CBF) is considered to be important in inner
      ear pathology. However, direct measurement of CBF is difficult and has not been
      investigated in combination with hearing function. Six guinea pigs were used to
      show feasibility of an animal model for the analysis of cochlear microcirculation
      by intravital microscopy in combination with investigation of the hearing
      threshold by brainstem response audiometry (ABR). By the application of sodium
      nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of
      measurements was shown by retest measurements. Mean baseline velocity of CBF was
      109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean
      hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased
      significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly
      to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a
      minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly
      increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity
      was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to
      157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in
      blood flow velocity occurred in spite of substantial hypotension as induced by a
      vasodilator. This may explain the fact that ABR threshold remained unchanged
      reflecting a maintained blood supply in this part of the brain. This technique
      can be used to evaluate effects of treatments aimed at cochlear microcirculation
      in inner ear pathologies.

PMID- 19597838
TI  - Comparison of different excimer laser ablation frequencies (50, 200, and 500 Hz).
AB  - PURPOSE: The aim of this study was to compare the influence of different excimer
      laser (193 nm) ablation frequencies (50, 200, and 500 Hz) on porcine cornea.
      METHODS: For this study, fresh porcine cadaver eyes were obtained from the
      butcher. PRK and LASIK were performed using a WaveLight Concept System 500
      excimer laser. Various repetition rates (50, 200, and 500 Hz) and intended
      corrections (between -3 and -9 D) were used. Corneal endothelium was investigated
      pre- and post-operatively with the endothelial cell microscope EM 1000 Tomey.
      Post-operatively, the corneas were embedded for light microscopic (HE,
      Picrosirius Red) and electron microscopic evaluation. RESULTS: The mean pre
      operative cell count was 2,953 (SD 149) and the mean post-operative cell count
      was 2,974 (SD 156). There was no difference between the pre- and post-operative
      cell count and the different ablation frequencies. The distribution of collagen
      fibers and keratocytes was comparable in all different ablation frequencies.
      Also, the ultrastructural evaluation of keratocytes and fibers, assessed with
      transmission electron microscopy, was equal in all three different ablation
      frequencies. CONCLUSIONS: The endothelial cell density and structural and ultra
      structural evaluation of the different ablation frequencies (50, 200, 500 Hz)
      showed no specific side-effects that could be associated with higher repetition
      rates. The quality of the ablation was comparable in all three different laser
      ablation frequencies. The 500-Hz excimer laser can provide the same ablation
      quality as slower platforms, but can also offer the advantage of requiring less
      treatment time than other laser platforms with lower repetition rates.

PMID- 19597837
TI  - Current trends in initial management of laryngeal cancer: the declining use of
      open surgery.
AB  - The role of open surgery for management of laryngeal cancer has been greatly
      diminished during the past decade. The development of transoral endoscopic laser
      microsurgery (TLS), improvements in delivery of radiation therapy (RT) and the
      advent of multimodality protocols, particularly concomitant chemoradiotherapy
      (CCRT) have supplanted the previously standard techniques of open partial
      laryngectomy for early cancer and total laryngectomy followed by adjuvant RT for
      advanced cancer. A review of the recent literature revealed virtually no new
      reports of conventional conservation surgery as initial treatment for early stage
      glottic and supraglottic cancer. TLS and RT, with or without laser surgery or
      CCRT, have become the standard initial treatments for T1, T2 and selected T3
      laryngeal cancer. Photodynamic therapy (PDT) may have an emerging role in the
      treatment of early laryngeal cancer. Anterior commissure involvement presents
      particular difficulties in application of TLS, although no definitive conclusions
      have been reached with regard to optimal treatment of these lesions. Results of
      TLS are equivalent to those obtained by conventional conservation surgery, with
      considerably less morbidity, less hospital time and better postoperative
      function. Oncologic results of TLS and RT are equivalent for glottic cancer, but
      with better voice results for RT in patients who require more extensive
      cordectomy. The preferred treatment for early supraglottic cancer, particularly
      for bulkier or T3 lesions is TLS, with or without postoperative RT. The Veterans
      Administration Study published in 1991 established the fact that the response to
      neoadjuvant CT predicts the response of a tumor to RT. Patients with advanced
      tumors that responded either partially or completely to CT were treated with RT,
      and total laryngectomy was reserved for non-responders. This resulted in the
      ability to preserve the larynx in a significant number of patients with locally
      advanced laryngeal cancer, while achieving local control and overall survival
      results equivalent to those achieved with initial total laryngectomy. Following
      this report, similar "organ preservation" protocols were employed in many
      centers. By 2003, results of the RTOG 93-11 trial, utilizing CCRT as initial
      treatment, were published, demonstrating a higher rate of laryngeal preservation
      with this protocol. Surgery was reserved for treatment failures. This concept
      changed the paradigm for management of advanced laryngeal cancer, greatly
      reducing the number of laryngectomies performed. While supracricoid laryngectomy
      has been employed for selected patients, total laryngectomy is the usual
      procedure for salvage of failure after non-surgical treatment.

PMID- 19597839
TI  - Effects of the multiple polyadenylation signal AAUAAA on mRNA 3'-end formation
      and gene expression.
AB  - Polyadenylation (poly(A)) of eukaryotic mRNA is a critical step for gene
      expression. In plants, poly(A) signals leading to the formation of polyadenosine
      tails after mRNAs include the far upstream elements, the AAUAAA-like signals, and
      the mRNA cleavage sites for poly(A). Multiple AAUAAA signals leading to
      alternative polyadenosine formation have been found in many genes, but the
      effects of each AAUAAA signal on gene expression remain to be uncovered. A DNA
      fragment, whose transcript contains two canonical AAUAAA signals from the 3'
      untranslation region of endochitinase gene of tobacco (Nicotiana tabacum L. cv.
      W38), was mutated and constructed into the downstream of beta-glucuronidase (GUS)
      coding region. Transient expression of GUS gene from these constructs indicated
      that the distal AAUAAA signal from the stop codon was more important than the
      proximal one in stimulating gene expression. Also, the sequence rather than the
      distance between the stop codon and the AAUAAA signal region was critical for
      gene expression. Transgenic tobaccos with these constructs were also generated,
      and the position of the polyadenosine tail formation in this region was mapped.
      Results revealed that both AAUAAA signals were functional, and that polyadenosine
      tails of most transcripts were directed by the distal AAUAAA signal. Finally, the
      RNA stabilities of these variants in transgenic plants were measured. RNAs from
      the variants with the functional distal AAUAAA signal were more stable than those
      with the functional proximal one only. The possible secondary structure in this
      poly(A) signal region was predicted and discussed.

PMID- 19597840
TI  - A volumetric study of the corpus callosum in 20s and 40s Korean people.
AB  - The purpose of this study was to measure the average corpus callosum volume of
      normal Koreans (aged in their 20s or 40s) and to analyze the effects of gender,
      age, and body parameters, such as height and weight on corpus callosum size.
      Magnetic resonance brain images were recorded for 68 people in their 20s (29 men,
      39 women) and 91 in their 40s (36 men, 55 women). Intracranial volume was
      calculated using cerebral size and corpus callosum volume was normalized by
      covariance method. To investigate the effect of gender and age on corpus callosum
      volume, two-way analysis of variance, which used gender (two levels) and age (two
      levels) as independent variables, was employed. Multiple regression analysis was
      carried out to investigate the effect of body parameters, such as height and
      weight, according to the age and gender on the changes in corpus callosum volume.
      The average corpus callosum volume of Korean men (11.09 cm(3)) was larger than
      that of Korean women (9.61 cm(3)). There was no significant difference in corpus
      callosum volume between 20s (10.43 cm(3)) and 40s (10.12 cm(3)). There was a
      positive relationship between body weight and corpus callosum volume for 20s, but
      not for 40s.

PMID- 19597841
TI  - Tentative identification of glycerol dehydrogenase as Escherichia coli K1
      virulence factor cglD and its involvement in the pathogenesis of experimental
      neonatal meningitis.
AB  - Escherichia coli (E. coli) is the most common gram-negative organism causing
      meningitis during the neonatal period. The mechanism involved in the pathogenesis
      of E. coli meningitis remains unclear. We previously identified a pathogenicity
      island GimA (genetic island of meningitic E. coli containing ibeA) from the
      genomic DNA library of E. coli K1, which may contribute to the E. coli invasion
      of the blood-brain barrier (BBB). CglD is one of the genes in GimA, and its
      function remains unknown. In order to characterize the role of cglD in the E.
      coli meningitis, an isogenic in-frame cglD deletion mutant of E. coli K1 was
      generated. The results showed that the median lethal dose of the cglD deletion
      mutant strain was significant higher than that of parent E. coli K1 strain, and
      the cglD deletion in E. coli K1 prolonged survival of the neonatal rats in
      experimental meningitis. However, deletion of cglD has no effect on the
      penetration of E. coli K1 through BBB in vitro and in vivo. Furthermore, our
      results showed that deletion of cglD in E. coli K1 attenuated cerebrospinal fluid
      changes, meningeal thickening, and neutrophil infiltration in the cerebral cortex
      in the neonatal rats with experimental meningitis. Additional results showed that
      the role of CglD in neonatal meningitis may be associated with its activity of
      glycerol dehydrogenase. Taken together, our study suggested that CglD is a
      virulence factor of E. coli K1 contributed to the development of neonatal
      meningitis.

PMID- 19597842
TI  - Fat and fat-free mass in Nepalese children: an assessment of nutritional status.
AB  - The aims of the present study were to determine the body composition and to
      assess the nutritional status on the basis of body composition parameters in
      Nepalese children. Body fat percentage (BF%), fat mass (FM), and fat-free mass
      (FFM) of 1,988 (1,016 boys and 972 girls) Nepalese children aged 6 to 10 years
      were calculated from triceps and subscapular skinfolds. FM and FFM were then
      divided by height-squared in meter to determine the fat mass index (FMI) and fat
      free mass index (FFMI), respectively. Growth curves of BF% and FFM for Nepalese
      children remained at a low level compared to international data. BF%, FM, and FMI
      of Nepalese girls were significantly (p < 0.001) higher than Nepalese boys,
      whereas FFM and FFMI of Nepalese boys were significantly (p < 0.001) higher than
      Nepalese girls of all age groups. BF%, FM, and FFM were significantly correlated
      with almost all anthropometric parameters in both sexes. Growth curves of BF% and
      FFM showed that the undernutrition prevailed in Nepalese children. BF% and FFM
      were good indicators for measuring nutritional status in Nepalese children.
      Sexual dimorphism of fat patterning was present in Nepalese children.

PMID- 19597843
TI  - Kinetic analysis of antibody responses to Blastocystis hominis in sera and
      intestinal secretions of orally infected mice.
AB  - The kinetics of antibody production against Blastocystis hominis, an emerging
      infectious protozoan parasite which causes intestinal disorder in humans and
      animals, was studied. Sera and intestinal secretions were collected from B.
      hominis-immunized Balb/C mice for 8 weeks. Flow cytometry was used to monitor the
      levels of immunoglobulins A (IgA), G (IgG), and M (IgM) from both types of
      biological samples. The kinetic profile derived from flow cytometry analysis
      revealed that IgM led the early immune action against B. hominis infection in
      immune sera while IgA was the predominant antibody isotype in intestinal
      secretions. Western blotting revealed an array of antigens recognized by both
      serum and intestinal secretion antibodies. Immunoreactive B. hominis soluble
      proteins with molecular weights ranging from 28.2 to 77.6 kDa were detected by
      serum antibodies and 15.1 to 117.5 kDa by secretory antibodies. These antigens
      may be cytoplasmic or membrane-bound as determined through indirect fluorescent
      antibody test. Moreover, two immunogens (39.8 and 77.6 kDa) were commonly
      recognized by serum antibodies, one (70.8 kDa) by secretory antibodies and two
      (55.0 and 56.2 kDa) by both serum and secretory antibodies, suggesting a possible
      target in the further understanding of B. hominis pathogenicity, discovery of
      virulence factors, and development of immunology-based diagnostic protocols and
      alternative modes of treatment.

PMID- 19597846
TI  - Syndecans as receptors and organizers of the extracellular matrix.
AB  - Syndecans are type I transmembrane proteins having a core protein modified with
      glycosaminoglycan chains, most commonly heparan sulphate. They are an ancient
      group of molecules, present in invertebrates and vertebrates. Among the plethora
      of molecules that can interact with heparan sulphate, the collagens and
      glycoproteins of the extracellular matrix are prominent. Frequently, they do so
      in conjunction with other receptors, most notably the integrins. For this reason,
      they are often referred to as "co-receptors". However, just as with integrins,
      syndecans can interact with actin-associated proteins and signalling molecules,
      such as protein kinases. Some aspects of syndecan signalling are understood but
      much remains to be learned. The functions of syndecans in regulating cell
      adhesion and extracellular matrix assembly are described here. Evidence from null
      mice suggests that syndecans have roles in postnatal tissue repair, inflammation
      and tumour progression. Developmental deficits in lower vertebrates in which
      syndecans are eliminated are also informative and suggest that, in mammals,
      redundancy is a key issue.

PMID- 19597844
TI  - Clear and independent associations of several HLA-DRB1 alleles with differential
      antibody responses to hepatitis B vaccination in youth.
AB  - To confirm and refine associations of human leukocyte antigen (HLA) genotypes
      with variable antibody (Ab) responses to hepatitis B vaccination, we have
      analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(
      )) enrolled into prospective studies. In univariate analyses that focused on HLA
      DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and
      DRB1*0701 were negatively associated with the responder phenotype (serum Ab
      concentration > or = 10 mIU/mL) (P = 0.026 and 0.043, respectively).
      Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non
      responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum
      Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000
      mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with
      the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These
      immunogenetic relationships were all independent of non-genetic factors,
      including HIV-1 infection status and immunodeficiency. Alternative analyses
      confined to HIV(+) youth or Hispanic youth led to similar findings. In contrast,
      analyses of more than 80 non-coding, single nucleotide polymorphisms within and
      beyond the three HLA class II genes revealed no clear associations. Overall,
      several HLA-DRB1 alleles were major predictors of differential Ab responses to
      hepatitis B vaccination in youth, suggesting that T-helper cell-dependent
      pathways mediated through HLA class II antigen presentation are critical to
      effective immune response to recombinant vaccines.

PMID- 19597845
TI  - Familial autosomal dominant reflex epilepsy triggered by hot water maps to 4q24
      q28.
AB  - Hot water epilepsy is a reflex or sensory epilepsy in which seizures are
      triggered by the stimulus of bathing in hot water. Although there is evidence of
      a genetic basis to its etiology, no gene associated with this disorder has so far
      been found. In order to identify the genetic locus involved in the
      pathophysiology of hot water epilepsy, we performed a genome-wide linkage
      analysis in a four-generation family manifesting the disorder in an autosomal
      dominant manner. Significant linkage was detected on chromosome 4q24-q28, with
      the highest two-point LOD score of 3.50 at recombination value (theta) of 0 for
      the marker D4S402. Centromere-proximal and centromere-distal boundaries of this
      locus were defined by the markers D4S1572 and D4S2277, respectively. The critical
      genetic interval spans 22.5 cM and corresponds to about 24 megabases of DNA. The
      genes NEUROG2, ANK2, UGT8 and CAMK2D, which are known to be expressed in human
      brain, are strong positional candidates and we propose to examine these and other
      genes in the locus to identify the causative gene for this intriguing form of
      epilepsy.

PMID- 19597848
TI  - Solar ultraviolet radiation alters alder and birch litter chemistry that in turn
      affects decomposers and soil respiration.
AB  - Solar ultraviolet (UV)-A and UV-B radiation were excluded from branches of grey
      alder (Alnus incana) and white birch (Betula pubescens) trees in a field
      experiment. Leaf litter collected from these trees was used in microcosm
      experiments under laboratory conditions. The aim was to evaluate the effects of
      the different UV treatments on litter chemical quality (phenolic compounds, C, N
      and lignin) and the subsequent effects of these changes on soil fauna and
      decomposition processes. We measured the decomposition rate of litter, growth of
      woodlice (Porcellio scaber), soil microbial respiration and abundance of
      nematodes and enchytraeid worms. In addition, the chemical quality of woodlice
      feces was analyzed. The exclusion of both UV-A and UV-B had several effects on
      litter chemistry. Exclusion of UV-B radiation decreased the C content in litter
      in both tree species. In alder litter, UV exclusion affected concentration of
      phenolic groups variably, whereas in birch litter there were no significant
      differences in phenolic compounds. Moreover, further effects on microbial
      respiration and chemical quality of woodlice feces were apparent. In both tree
      species, microbial CO(2) evolution was lower in soil with litter produced under
      exclusion of both UV-A and UV-B radiation when compared to soil with control
      litter. The N content was higher in the feces of woodlice eating alder litter
      produced under exclusion of both UV-A and UV-B compared to the control. In
      addition, there were small changes in the concentration of individual phenolic
      compounds analyzed from woodlice feces. Our results demonstrate that both UV-A
      and UV-B alter litter chemistry which in turn affects decomposition processes.

PMID- 19597847
TI  - Experimental evolution of resistance against a competing fungus in Drosophila
      melanogaster.
AB  - Competition between microorganisms and arthropods has been shown to be an
      important ecological interaction determining animal development and spatial
      distribution patterns in saprophagous communities. In fruit-inhabiting
      Drosophila, variation in insect developmental success is not only determined by
      species-specific effects of various noxious filamentous fungi but, as suggested
      by an earlier study, also by additive genetic variation in the ability to
      successfully withstand the negative impact of the fungi. If this variation
      represents a direct adaptive response to the degree to which insect breeding
      substrates are infested with harmful fungi, genetic variation for successful
      development in the presence of fungi could be maintained by variation in
      infestation of resource patches with fungi. We selected for the ability to resist
      the negative influence of mould by maintaining replicated Drosophila melanogaster
      populations on substrates infested with Aspergillus nidulans. After five cycles
      of exposure to the fungus during the larval stage, the selected populations were
      compared with unselected control populations regarding adult survival and
      reproduction to reveal an evolved resistance against the fungal competitor. On
      fungus-infested larval feeding substrates, emerged adults from mould-selected
      populations had higher survival rates and higher early fecundity than the control
      populations. In the unselected populations, females had higher mortality rates
      than males, and a high proportion of both females and males appeared to be unable
      to lay eggs or fertilise eggs, respectively. When larvae developed on non
      infested food we found indications of a loss of resistance to abiotic and
      starvation stress in the adult stage in flies from the selected populations. This
      suggests that there are costs associated with an increase in resistance against
      the microbial competitor. We discuss the underlying mechanisms that might have
      selected for increased resistance against harmful fungi.

PMID- 19597849
TI  - How do beetle assemblages respond to cyclonic disturbance of a fragmented
      tropical rainforest landscape?
AB  - There are surprisingly few studies documenting effects of tropical cyclones
      (including hurricanes and typhoons) on rainforest animals, and especially
      insects, considering that many tropical forests are frequently affected by
      cyclonic disturbance. Consequently, we sampled a beetle assemblage inhabiting 18
      upland rainforest sites in a fragmented landscape in north-eastern Queensland,
      Australia, using a standardised sampling protocol in 2002 and again 12 months
      after the passage of Severe Tropical Cyclone Larry (March 2006). The spatial
      configuration of sites allowed us to test if the effects of a cyclone and those
      from fragmentation interact. From all insect samples we extracted 12,568 beetles
      of 382 species from ten families. Beetle species composition was significantly
      different pre-and post-cyclone although the magnitude of faunal change was not
      large with 205 species, representing 96% of all individuals, present in both
      sampling events. Sites with the greatest changes to structure had the greatest
      changes in species composition. At the site level, increases in woody debris and
      wood-feeding beetle (Scolytinae) counts were significantly correlated but changes
      in the percent of ground vegetation were not mirrored by changes in the abundance
      of foliage-feeding beetles (Chrysomelidae). The overall direction of beetle
      assemblage change was consistent with increasing aridity, presumably caused by
      the loss of canopy cover. Sites with the greatest canopy loss had the strongest
      changes in the proportion of species previously identified in the pre-cyclone
      study as preferring arid or moist rainforest environments. The magnitude of
      fragmentation effects was virtually unaltered by the passage of Cyclone Larry. We
      postulate that in the short-term the effects of cyclonic disturbance and forest
      fragmentation both reduce the extent of moist, interior habitat.

PMID- 19597850
TI  - [Desire for early retirement and chronic back pain therapy].

PMID- 19597851
TI  - The single transoral approach for Os odontoideum with irreducible atlantoaxial
      dislocation.
AB  - We report a 52-year-old female patient with a 2-year history of local neck pain,
      decreased cervical spine rotation, progressive numbness and weakness of both
      arms. Preoperative, dynamic X-rays, computed tomography, three-dimensional
      computed tomography demonstrated a displaced Os odontoideum with irreducible
      Subluxation of C1/2. We used a single transoral approach release, reduction using
      an assistance of skull traction, bone fusion and stabilization in the treatment
      of Os odontoideum with irreducible alantoaxial dislocation. Postoperative, the
      patient was free of all symptoms and X-rays taken showed a stable fusion of C1/2
      at 6th postoperative month. This technique in the treatment of Os odontoideum
      with irreducible alantoaxial dislocation is atraumatic and effective. And
      preoperative dynamic X-rays, computed tomography, three-dimensional computed
      tomography and MRI scans provided an invaluable aid to select this operative
      procedure.

PMID- 19597852
TI  - Expression profile and synthesis of different collagen types I, II, III, and V of
      human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate
      treatment.
AB  - Bisphosphonates (BP) are used in the treatment of malignant osteolytic processes
      and postmenopausal osteoporosis. There have been a number of incidents in
      patients treated with BP. The incidents are described as an osteonecrosis of the
      jaw (ONJ). The main medications associated with these reports are zoledronic acid
      (ZOL) and pamidronate (PAM). The clinical presentations describe a deterioration
      of the jaw bones and surrounding tissues. The purpose of this study was to
      investigate expression of collagen types I, II, III, and V in human gingival
      fibroblasts, osteoblasts, and osteosarcoma cells (SaOS-2 cells) by ELISA and
      reverse transcription PCR (RT-PCR) with constant exposure (28 days) to ZOL and
      PAM. The real-time PCR indicates that ZOL inhibited gene expression below 16% at
      any concentration used. Hence, an amplification of extracellular matrix was only
      possible for PAM at concentrations of 1 microM. The following expression levels
      were for fibroblasts at a maximum of 31%, exceptionally high for the osteoblasts
      at 56%, and for SaOS-2 cells the peak was 14%. Principally, a decreased
      production of collagen was measured. With this in vitro study, we demonstrated
      how negatively influencing a long exposure to ZOL and PAM can be. Therefore, a
      reduction in extracellular matrix production of these cell lines under BP
      exposure could be a possible clinical indication as to why patients experience
      ONJ and have wound healing problems. However, it remains uncertain as to why an
      osteonecrosis is mainly found in the jaws and not other bones. As there are many
      influencing factors, further investigation needs to be pursued.

PMID- 19597853
TI  - Long-tailed macaques display unexpected waiting abilities in exchange tasks.
AB  - The ability of animals to delay gratification is crucial for complex goal
      directed action. It may help them in making effective decisions when facing a
      choice. We tested the ability of nine long-tailed macaques (Macaca fascicularis)
      to delay gratification in several experiments. In exchange tasks, subjects had to
      keep a small piece of cookie before returning it to an experimenter in order to
      get a larger food amount. Results showed that animals could wait between 10 s and
      10 min depending on individual and sizes of reward. In another experiment,
      subjects could immediately give back the initial piece of cookie then wait for
      the return. Their performances more than doubled, demonstrating the role of
      consumption inhibition in postponing gratification. Such achievements underscore
      delays of gratification which until now were not thought possible in monkeys.
      Finally, subjects were presented with an accumulation of food pieces added at
      short intervals until they seized them. They mostly waited between 30 s and 1
      min, which points at the consistency of our data, compared to those of other
      studies. Our results indicate that long-tailed macaques anticipated the duration
      of delays. We may account for their remarkable performances by their achievements
      in the social context.

PMID- 19597854
TI  - Signals use by leaders in Macaca tonkeana and Macaca mulatta: group-mate
      recruitment and behaviour monitoring.
AB  - Animals living in groups have to make consensus decisions and communicate with
      each other about the time, or the direction, in which to move. In some species,
      the process relies on the proposition of a single individual, i.e. a first
      individual suggests a movement and the other group members decide whether or not
      to join this individual. In Tonkean (Macaca tonkeana) and rhesus macaques (Macaca
      mulatta), it has been observed that this first individual displays specific
      signals at departure. In this paper, we aimed to explore the function of such
      behaviours, i.e. if these behaviours were recruitment signals or only cues about
      the motivation of the first departed individual. We carried out temporal analyses
      and studied the latencies of the first departed individual's behaviours and of
      the joining of other group members. We also assessed whether the social style of
      a species in terms of dominance and kinship relationships influenced the patterns
      of signal emissions. We then analyzed how the first departed individual decided
      to make a pause or to stop it according to the identities of group members that
      joined the collective movement. Results showed that Tonkean macaques and rhesus
      macaques seemed to use back-glances to monitor the joining of other group members
      and pauses to recruit such individuals. This was especially the case for highly
      socially affiliated individuals in Tonkean macaques and kin-related individuals
      in rhesus macaques. Moreover, back-glances and pauses disappeared when such
      individuals joined the first departed individual. From these results, we
      suggested that such behaviour could be considered intentional. Such findings
      could not be highlighted without temporal analyses and accurate observations on
      primate groups in semi-free ranging conditions.

PMID- 19597855
TI  - The equivocal appendix at CT: prevalence in a control population.
AB  - The purpose of the study was to determine the prevalence of appendices with an
      equivocal appearance at computed tomography (CT) in a control population. We
      retrospectively identified a control population of 150 patients who underwent CT
      of the abdomen and pelvis for evaluation of hematuria (without abdominal pain,
      fever, or colonic disease). One reader measured the diameter of the appendix and
      noted if the appendix was either isodense in appearance or airless and fluid
      filled. Sixty-seven of 150 cases (44.6%) demonstrated appendiceal diameter
      greater than 6 mm. The appendix was collapsed or isodense in 34/150 cases
      (22.7%). Only ten of 150 or 6.6% of cases were isodense in combination with
      diameter greater than 6 mm, and none had diameter greater than 10 mm. Only one of
      150 cases (0.67%) demonstrated airless fluid within the lumen, and the appendix
      measured less than 6 mm. While the diameter of the normal appendix is frequently
      greater than 6 mm, none measured greater than 10 mm in combination with ambiguous
      morphology. Furthermore, in the normal appendix, airless fluid filling the lumen
      is a rare appearance with a prevalence of less than 1%. While appendicitis could
      undoubtedly occur in an isodense appendix between 6 and 10 mm in diameter, such
      an appearance can occur in up to 6.6% of the normal population.

PMID- 19597856
TI  - Porcine muscle sensory attributes associate with major changes in gene networks
      involving CAPZB, ANKRD1, and CTBP2.
AB  - Principal component analysis of traits related to carcass and meat properties
      were combined with microarray expression data for the identification of
      functional networks of genes and biological processes taking place during the
      conversion of muscle to meat. Principal components (PCs) with high loadings of
      meat quality traits were derived from phenotypic data of 572 animals of a porcine
      crossbreed population. Microarray data of 74 M. longissimus dorsi samples were
      correlated with PC datasets. Lists of significantly correlated genes were
      analyzed for enrichment of functional annotation groups as defined in the Gene
      Ontology and Kyoto Encyclopedia of Genes and Genomes databases as well as the
      Ingenuity Pathways Analysis library. Ubiquitination, phosphorylation,
      mitochondrion dysfunction, actin, integrin, platelet-derived growth factor,
      epidermal growth factor, vascular endothelial growth factor, and Ca signaling
      pathways are correlated with meat quality. Among the significantly trait
      associated genes, CAPZB, ANKRD1, and CTBP2 are promoted as candidate genes for
      meat quality that provide a link between the highlighted pathways. Knowledge of
      the relevant biological processes and the differential expression of members of
      the pathway will provide tools that are predictive for traits related to meat
      quality and that may also be diagnostic for many muscle defects or damages
      including muscle atrophy, dystrophy, and hypoxia.

PMID- 19597858
TI  - Phytoextraction of Pb and Cd by the Mediterranean saltbush (Atriplex halimus L.):
      metal uptake in relation to salinity.
AB  - BACKGROUND, AIM, AND SCOPE: The success of phytoextraction depends upon the
      identification of suitable plant species that hyperaccumulate heavy metals and
      produce large amounts of biomass using established agricultural techniques. In
      this study, the Mediterranean saltbush Atriplex halimus L., which is a C4
      perennial native shrub of Mediterranean basin with an excellent tolerance to
      drought and salinity, is investigated with the main aim to assess its
      phytoremediation potential for Pb and Cd removal from contaminated soils. In
      particular, the influence of soil salinity in metal accumulation has been studied
      as there is notable evidence that salinity changes the bioavailability of metals
      in soil and is a key factor in the translocation of metals from roots to the
      aerial parts of the plant. MATERIALS AND METHODS: Three pot experiments were
      conducted under greenhouse conditions for a 10-week period with A. halimus grown
      in soil artificially polluted with 20 ppm of Cd and/or 800 ppm of Pb and
      irrigated with three different salt solutions (0.0%, 0.5%, and 3.0% NaCl). Soil
      measurements for soil characterization were performed with the expiration of the
      first week of plant exposure to metals and NaCl, and at the end of the
      experimental period, chlorophyll content, leaf protein content, leaf specific
      activity of guaiacol peroxidase (EC 1.11.1.7), shoot water content, biomass, and
      Cd and Pb content in the plant tissues were determined. Additionally, any
      symptoms of metal or salt toxicity exhibited by the plants were visually noted
      during the whole experimental period. RESULTS: The experimental data suggest that
      increasing salinity increases cadmium uptake by A. halimus L. while in the case
      of lead there was not a clear effect of the presence of salt on lead accumulation
      in plant tissues. A. halimus developed no visible signs of metal toxicity; only
      salt toxicity symptoms were observed in plants irrigated with 3% NaCl solutions.
      Chlorophyll content, leaf protein content, shoot water content, and biomass were
      not negatively affected by the metals; instead, there was even an increase in the
      amount of photosynthetic pigments in plants treated with both metals and
      salinity. The specific activity of guaiacol peroxidase seems to have a general
      tendency for increase in plants treated with the metals in comparison with the
      respective controls but a statistically significant difference exists only in
      plants treated with the metal mixture and saline conditions. DISCUSSION: The data
      revealed that lead and cadmium accumulation in plant tissues was kept generally
      at low levels. Salinity was found to have a positive effect on cadmium uptake by
      the plant and this may be related to a higher bioavailability of the metal in
      soil due to decreased Cd sorption on soil particles. On the other hand, salinity
      did not influence in a clear way the uptake of Pb by the plant probably because
      of lead's limited mobility in soils and plant tissues. Cd and Pd usually decrease
      the chlorophyll content and biomass and change water relations in plants;
      however, A. halimus was found not to be affected indicating that it is a Cd- and
      Pb-tolerant plant. Guaiacol peroxidase activity as one of the parameters
      expressing oxidative damage and extent of stress in plants was not generally
      found to be significantly affected under the presence of metals in most plants
      suggesting that the extent of stress in plants was minimal, while only for plants
      treated with the metal mixture and low salinity the enzyme activity was elevated
      confirming that this enzyme serves as an antioxidative tool against the reactive
      oxygen species produced by the metals. CONCLUSIONS: Atriplex halimus L. is a Pb-
      and Cd-tolerant plant but metal concentrations achieved in plant tissues were
      kept generally at low levels; however, metal accumulation in shoots, especially
      for Cd, considered together with its high biomass production, rapid growth, and
      deep root system able to cope with poor structure and xeric characteristics of
      several polluted soils suggest that this plant deserves further investigation.
      RECOMMENDATIONS AND PERSPECTIVES: Phytoextraction by halophytes is a promising
      alternative for the remediation of heavy metal contaminated sites affected by
      salinity since saline depressions often indicate sites of industrial effluents
      accumulation, contaminated by heavy metals, including Pb and Cd. Halophytes are
      also promising candidates for the removal of heavy metals from non-saline soils.
      Furthermore, the use of such plants can be potentially viewed as an alternative
      method for soil desalination where salt is removed from the soil instead of being
      washed downwards by water or other solutions.

PMID- 19597857
TI  - Enhanced expression of engineered ACA-less beta-1, 6-N-acetylglucosaminidase
      (dispersin B) in Escherichia coli.
AB  - beta-1,6-N-Acetylglucosaminidase (dispersin B), which cleaves poly-ss-(1,6)
      linked N-acetylglucosamine, is encoded by dspB of Aggregatibacter
      actinomycetemcomitans. To enhance the production of dispersin B, we engineered
      dspB to transcribe mRNAs devoid of the trinucleotide ACA. Transcription and
      translation levels of ACA-less and wild-type dspB expressed in Escherichia coli
      (E. coli) under T5 and T7 promoters were analyzed by real-time RT-PCR and protein
      quantification, respectively. The ACA-less dspB mRNA level was significantly
      higher (P < 0.01) and produced 77.6 and 34.9% more dispersin B than wild-type
      dspB expressed under T7 and T5 promoters, respectively. Dispersin B expression
      under T7 promoter caused a 98-99.5% drop in the glyceraldehyde-3-phosphate
      dehydrogenase (gapA) mRNA level, which was not observed with T5 promoter. Fusion
      of green fluorescent protein (GFP) with dispersin B allowed rapid quantification
      of dispersin B production by measuring fluorescence intensity in culture broth.
      Although the cultures containing 0.1% glucose showed sustained increase in
      dispersin B-GFP production until 12 h, no significant increase in dispersin B
      activity was observed beyond 4 and 6 h after induction when expressed under T7
      and T5 promoters, respectively. This study demonstrates the effectiveness of ACA
      less mRNA and the advantage of GFP tagging for enhanced dispersin B production
      and quantification, which could be adapted for improving the production of other
      commercially important proteins in E. coli.

PMID- 19597859
TI  - Accuracy of different reduced versions of a validated food-frequency
      questionnaire in italian men and women.
AB  - This study aimed to explore how possible it would be to reduce the length of a
      food-frequency questionnaire (FFQ) while maintaining adequate accuracy. This FFQ
      was validated in women in a previous study by our group, whereas the validation
      in men was one of the aims of the present study. A 15-item FFQ was administered
      to 136 men and 211 women (age range 25-75 years) recruited by proportional age
      stratified sampling, who agreed to fill in a 14-day diet diary. For the
      intermediate version of the FFQ we considered only eight items in women and 10 in
      men. For the very short version we considered only three items. The positive
      likelihood ratio was markedly lower for the very short version (men = 1.2 and
      women = 1.5) with respect to the intermediate version (men = 6 and women = 6.3)
      and the 15-item version (men = 19.6 and women = 19.9). The specificity of the
      very short version was low (22.2% for men and 35.2% for women). The area under
      ROC curve of the three-item FFQ was significantly lower with respect to the other
      two versions. In conclusion, our study suggests that the shortest version of the
      FFQ could be usefully employed only in those clinical settings where the main
      objective is the identification of individuals who do not have a low calcium
      intake. ROC analysis and posttest probability calculated by positive likelihood
      ratio may represent an optimal method for assessing the accuracy of FFQs.

PMID- 19597860
TI  - A neonate with cyanosis and tortuous great arteries.
AB  - This report describes an unusual case with tortuosity of the great vessels in a
      neonate who presented at birth with cyanosis. The diagnosis was made with
      magnetic resonance imaging (MRI), then confirmed by genetic analysis.

PMID- 19597861
TI  - Scoliosis in patients with aortic coarctation and patent ductus arteriosus: does
      standard posterolateral thoracotomy play a role in the development of the lateral
      curve of the spine?
AB  - The aim of this study was to determine the influence of lateral thoracotomy on
      the development of scoliosis in subjects undergoing repair of coarctation of the
      aorta (CoA) and patent ductus arteriosus (PDA). A group of 133 patients with CoA
      and PDA was evaluated. Forty-five patients with CoA and 38 with PDA underwent
      surgery using standard posterolateral thoracotomy (operative group), whereas 12
      patients with CoA and 31 with PDA were treated using balloon dilatation and stent
      or coil implantation (nonoperative group). A spinal examination, together with
      the evaluation of chest and spinal roentgenograms, was conducted. Among the
      operated patients, 62% of those with CoA and 55% of those with PDA had clinical
      scoliosis. In the nonoperated patients, scoliosis was present in only 25% of
      those with CoA and 16% of those with PDA. Scoliosis ranged between 10 degrees and
      42 degrees . In 89% of the operated patients with CoA and 76% of those with PDA
      the curve was thoracic; in 46% of the CoA group and 57% of the PDA group the
      curve was left-sided. All curves were right-sided in nonoperated subjects.
      Scoliosis in the operated group was higher in male than in female subjects (63%
      vs. 60% in CoA and 86% vs. 37% in PDA). The prevalence of scoliosis after
      standard posterolateral thoracotomy was significantly higher than after
      nonsurgical treatment methods in the CoA and PDA groups as well as in the general
      population. The rate of single thoracic and the rate of left-sided thoracic
      curves in patients after thoracotomy is higher than in nonoperated patients or in
      those with idiopathic scoliosis. The rate of scoliosis after thoracotomy is
      higher in male than female patients, especially after thoracotomy for PDA.

PMID- 19597862
TI  - The occurrence of multidrug-resistant Pseudomonas aeruginosa on hydrocarbon
      contaminated sites.
AB  - The main aim of this paper was the comprehensive estimation of the occurrence
      rate and the antibiotic-resistance conditions of opportunistic pathogen
      Pseudomonas aeruginosa in hydrocarbon-contaminated environments. From 2002 to
      2007, 26 hydrocarbon-contaminated sites of Hungary were screened for the
      detection of environmental isolates. Altogether, 156 samples were collected and
      examined for the determination of appearance, representative cell counts, and
      antibiotic-resistance features of P. aeruginosa. The detected levels of minimal
      inhibitory concentrations of ten different drugs against 36 environmental strains
      were compared to the results of a widely used reference strain ATCC 27853 and
      four other clinical isolates of P. aeruginosa. Based on our long-term experiment,
      it can be established that species P. aeruginosa was detectable in case of 61.5%
      of the investigated hydrocarbon-contaminated sites and 35.2% of the examined
      samples that shows its widespread occurrence in polluted soil-groundwater
      systems. In the course of the antibiotic-resistance assay, our results determined
      that 11 of the examined 36 environmental strains had multiple drug-resistance
      against several clinically effective antimicrobial classes: cephalosporins, wide
      spectrum penicillins, carbapenems, fluoroquinolones, and aminoglycosides. The
      fact that these multiresistant strains were isolated from 8 different hydrocarbon
      contaminated sites, mainly from outskirts, confirms that multiple drug-resistance
      of P. aeruginosa is widespread not only in clinical, but also in natural
      surroundings as well.

PMID- 19597863
TI  - Transaxillary breast augmentation: a prospective comparison of subglandular,
      subfascial, and submuscular implant insertion.
AB  - BACKGROUND: During the last decades transaxillary breast augmentation (TBA) has
      gained worldwide acceptance. Breast augmentation via transaxillary access
      endoscopically assisted in the subglandular, subfascial, and submuscular planes
      has been previously described. Although TBA is a well-studied procedure, few
      reports exist concerning the subfascial plane of implant insertion and none exist
      comparing the three different planes of insertion by TBA. METHODS: A perspective
      study to evaluate the outcomes, complications, and patient satisfaction of TBA
      using the three different planes of implant insertion was performed during 2004
      2005. Fifty-three patients fulfilled the inclusion criteria. They were randomly
      divided into three groups corresponding to the three planes of silicone
      insertion. All patients had a silicone texturized implant that ranged from 190 to
      300 cc. Overall satisfaction with the breast appearance after TBA was rated on a
      scale of 1-5, where 1 is poor, 2 is fair, 3 is good, 4 is very good, and 5 is
      excellent. The evaluation was made at the follow-up times of 6 months and 3
      years. RESULTS: There were 18 patients enrolled for the subcutaneous TBA (Group
      A), 18 for the subfascial TBA (Group B), and 17 for the submuscular TBA (Group
      C). Axillary incision-related complications occurred in 9% of the patients and
      included formation of a hypertrophic scar and small-wound dehiscence. There was
      no hematoma formation and no case of infection. There was one patient from Group
      A who developed seroma and was treated conservatively. Twenty-seven months
      postoperatively the same patient developed Baker III capsule contracture, which
      required silicone implant replacement in the subfascial plane. One case of
      stretch marks in a young nulliparous woman from Group B did not need treatment.
      One patient from Group A underwent implant exchange because of implant size
      dissatisfaction. Three patients in Group C had mild distortion of the implant
      during pectoral contracture. A meta-analysis of patient satisfaction 6 months and
      3 years after TBA is presented. CONCLUSION: Transaxillary breast augmentation
      provides consistent, satisfactory results with ease of dissection, when properly
      indicated. Although the subfascial augmentation mammaplasty has all the
      advantages of the subpectoral and subglandular augmentation mammaplasties and
      eliminates the disadvantages of increased postoperative discomfort, implant
      visibility, and distortion, patients of all three groups had similar rates of
      satisfaction. Further follow-up is needed in order to compare the long-term
      effects of the three different planes of insertion.

PMID- 19597864
TI  - Aesthetic quality of the nipple-areola complex in breast reconstruction with a
      new local graft technique.
AB  - BACKGROUND: Reconstruction of the nipple-areola complex (NAC) is the last stage
      of breast reconstruction and represents the search for symmetry in regard to the
      contralateral breast. The objective of this study was to present an areola
      reconstruction technique with local skin graft to improve the texture and aspect
      of the reconstructed areola, searching for a natural look. METHODS: This
      technique was performed on 122 patients who in the period from January 2000 to
      December 2005 were submitted to nipple and areola reconstruction. Once the
      position of the new nipple was determined, markings were made for the
      reconstruction of the areola. Then the external limit of the new areola was
      incised and the skin was centripetally deepidermized up to 85% of its diameter.
      After this procedure the detached skin was repositioned in its bed as a graft and
      sutured with 4.0 mononylon thread. Incisions with an 11-blade scalpel were then
      made in V and C forms associated with the detachment of this skin of the receptor
      area along the local graft so that at the end of the healing process they would
      determine alterations in the areolar texture mimicking the texture of a normal
      areola. All patients underwent tattooing 3 months after reconstruction of the NAC
      taking into account the different shades of the contralateral areola and nipple
      colors. RESULTS: The use of a local skin graft associated with C and V incisions
      allowed alteration in the texture of the reconstructed areola. The use of
      different ink shades for tattooing helped to give a tridimensional aspect to this
      areola. These factors determined a good aesthetic result in these patients.
      CONCLUSION: This areola reconstruction using a local skin graft allows change in
      the areola texture and a tridimensional aspect similar to that of a normal areola
      without the inconvenience of grafting from a distance.

PMID- 19597865
TI  - Abdominal fascial flaps for providing total implant coverage in one-stage breast
      reconstruction: an autologous solution.
AB  - BACKGROUND: Silicone implants are often used in immediate breast reconstruction.
      Complications associated with silicone-based implant reconstruction, such as
      capsular contracture, implant palpability, and visibility, are best avoided by
      placing the implant under a reliable soft-tissue cover such as the pectoralis
      major muscle. This muscle, however, is not always sufficient for complete
      coverage of the silicone implant. This is especially true for large implants. By
      including the fascia of the upper abdominal muscles in the reconstruction, this
      problem can be overcome. We describe our experience with one-stage breast
      reconstruction utilizing the fascia of the upper abdominal muscles to provide
      adequate soft-tissue coverage of the implant. METHODS: This technique was used in
      the reconstructions of ten patients over 4 years (2005-2009). This method was
      selected by the operating surgeon at the time of surgery if the pectoralis major
      muscle was felt to be of inadequate size to provide adequate implant coverage.
      The pectoralis major muscle was released from its sternal and caudal attachments
      to the chest wall. The rectus abdominis fascia and external oblique fascia were
      elevated as a combined cephalic-based flap. This fascial flap was advanced
      cranially and sutured to the released pectoralis major muscle after insertion of
      the implant. RESULTS: The mean size of the silicone implant was 448.2 cc and mean
      follow-up was 19.7 months. All implants were adequately covered with soft tissue
      at the end of each case. Complications included one patient with a hematoma, one
      patient with skin necrosis at the suture line, and one patient with an implant
      infection necessitating removal. CONCLUSION: There are many ways to provide soft
      tissue coverage of silicone breast implants in breast reconstruction. These
      include acellular dermis slings, polyglycolic mesh, deepithelialized skin, and
      muscle. The ideal soft-tissue cover would be supple, easily harvested, of minimal
      morbidity, of minimal cost, and preferably autologous. We feel that the technique
      described here has these qualities and allows for complete coverage of silicone
      implants. An additional benefit of this technique is that it helps to increase
      the definition of the inframammary sulcus. This method is a good alternative in
      providing implant coverage during breast reconstruction, especially when there is
      a large implant or small pectoralis major muscle.

PMID- 19597866
TI  - Predicting sustained fire spread in Tasmanian native grasslands.
AB  - Fire is widely used in conservation management of native grasslands. Burning is
      often carried out under conditions that are marginal for sustained fire spread,
      and therefore it would be useful to be able to predict fire sustainability. There
      is currently no model allowing such prediction in temperate grasslands. This
      study aims to identify the environmental variables that determine whether fires
      will sustain in native grasslands in Tasmania, Australia, and develop a model for
      predicting fire sustainability in this vegetation. Fuel characteristics and
      weather conditions were recorded for 111 test fires. Logistic regression modeling
      identified dead fuel moisture content, fuel load, and percentage dead fuel as
      predictors of fire sustainability. Classification tree modeling identified dead
      fuel moisture and fuel load threshold values for sustaining fires. There was also
      evidence indicating a percentage dead fuel threshold. The logistic regression
      model and a model combining the results of the classification tree and the
      percentage dead fuel threshold accurately predicted the outcomes of a small set
      of experimental fires. These models are likely to have utility in predicting fire
      sustainability in Tasmanian grasslands and are also likely to be applicable to
      similar grasslands elsewhere.

PMID- 19597867
TI  - The relative importance of road density and physical watershed features in
      determining coastal marsh water quality in Georgian Bay.
AB  - We used a GIS-based approach to examine the influence of road density and
      physical watershed features (watershed size, wetland cover, and bedrock type) on
      water quality in coastal marshes of Georgian Bay, Ontario. We created a GIS that
      included landscape information and water-quality data from a 9-year synoptic
      survey of 105 coastal marshes covering 28 quaternary watersheds. Multiple
      regressions and partial correlations were used to discern confounding effects of
      human-induced (road density) versus natural physical watershed determinants of
      water quality. Road density was the dominant factor influencing many water
      quality variables, showing positive correlations with specific conductivity
      (COND), total suspended solids (TSS), and inorganic suspended solids (ISS) and a
      negative correlation with overall Water Quality Index scores. Road density also
      showed positive correlations with total nitrate nitrogen (TNN) and total
      phosphorus (TP). By comparison, larger watershed area was the main factor leading
      to elevated TP concentrations. The proportion of the watershed occupied by
      wetlands explained the largest amount of variation in TNN concentrations
      (negative correlation) and was also negatively correlated with COND and
      positively correlated with TSS and ISS when we controlled for road density.
      Bedrock type did not have a significant effect in any of the models. Our findings
      suggest that road density is currently the overriding factor governing water
      quality of coastal marshes in Georgian Bay during the summer low-flow period. We
      recommend that natural variation in physical watershed characteristics be
      considered when developing water quality standards and management practices for
      freshwater coastal areas.

PMID- 19597868
TI  - The role of disaggregation of asset values in flood loss estimation: a comparison
      of different modeling approaches at the Mulde River, Germany.
AB  - In loss estimation there is a spatial mismatch of hazard data that are commonly
      modeled on an explicit raster level and exposure data that are often available
      only for aggregated administrative units. Usually disaggregation methods that use
      ancillary information to distribute lumped exposure data in a finer spatial
      resolution help to bridge this gap. However, the actual influence of different
      mapping techniques and ancillary data on the final loss estimation has not been
      analyzed yet. In this paper three methods are applied to disaggregate residential
      building assets using two kinds of land use/land cover (LULC) data. The resulting
      disaggregated assets are validated and compared using census data of the
      residential building number on the community and constituency level. In addition,
      the disaggregated assets are taken to estimate residential building losses due to
      the flood in August 2002 in 21 municipalities on the River Mulde in Saxony,
      Germany. Losses are calculated with the help of four loss models. In general,
      disaggregation helps to decrease the error variance within the loss estimation.
      It must, however, be stated that the application of sophisticated disaggregation
      methods does not lead to significant improvements compared to the straightforward
      binary method. Therefore more effort should instead be put into the provision of
      high-resolution LULC data. Finally, the remaining uncertainties in loss
      estimation are high and demand further improvements in all modeling aspects.

PMID- 19597869
TI  - Observations of atmospheric nitrogen and phosphorus deposition during the period
      of algal bloom formation in northern Lake Taihu, China.
AB  - Cyanobacterial blooms in Lake Taihu occurred at the end of April 2007 and had
      crucial impacts on the livelihood of millions of people living there. Excessive
      nutrients may promote bloom formation. Atmospheric nitrogen (N) and phosphorus
      (P) deposition appears to play an important role in algal bloom formation. Bulk
      deposition and rain water samples were collected respectively from May 1 to
      November 30, 2007, the period of optimal algal growth, to measure the bulk
      atmospheric deposition rate, wet deposition rate, and dry deposition rate for
      total nitrogen (TN; i.e., all species of nitrogen), and total phosphorus (TP;
      i.e., all species of phosphorus), in northern Lake Taihu, China. The trends of
      the bulk atmospheric deposition rate for TN and the wet deposition rate for TN
      showed double peaks during the observation period and distinct influence with
      plum rains and typhoons. Meanwhile, monthly bulk atmospheric deposition rates for
      TP showed little influence of annual precipitation. However, excessive rain may
      lead to high atmospheric N and P deposition rates. In bulk deposition samples,
      the average percentage of total dissolved nitrogen accounting for TN was 91.2%
      and changed little with time. However, the average percentage of total dissolved
      phosphorus accounting for TP was 65.6% and changed substantially with time.
      Annual bulk atmospheric deposition rates of TN and TP during 2007 in Lake Taihu
      were estimated to be 2,976 and 84 kg km(-2) a(-1), respectively. The results
      showed decreases of 34.4% and 78.7%, respectively, compared to 2002-2003. Annual
      bulk deposition load of TN for Lake Taihu was estimated at 6,958 t a(-1) in 2007
      including 4,642 t a(-1) of wet deposition, lower than the values obtained in 2002
      2003. This may be due to measures taken to save energy and emission control
      regulations in the Yangtze River Delta. Nevertheless, high atmospheric N and P
      deposition loads helped support cyanobacterial blooms in northern Lake Taihu
      during summer and autumn, the period of favorable algal growth.

PMID- 19597870
TI  - Situating hazard vulnerability: people's negotiations with wildfire environments
      in the U.S. southwest.
AB  - This article is based on a multimethod study designed to clarify influences on
      wildfire hazard vulnerability in Arizona's White Mountains, USA. Findings reveal
      that multiple factors operating across scales generate socially unequal wildfire
      risks. At the household scale, conflicting environmental values, reliance on fire
      insurance and firefighting institutions, a lack of place dependency, and social
      vulnerability (e.g., a lack of financial, physical, and/or legal capacity to
      reduce risks) were found to be important influences on wildfire risk. At the
      regional-scale, the shift from a resource extraction to environmental amenity
      based economy has transformed ecological communities, produced unequal social
      distributions of risks and resources, and shaped people's social and
      environmental interactions in everyday life. While working-class locals are more
      socially vulnerable than amenity migrants to wildfire hazards, they have also
      been more active in attempting to reduce risks in the aftermath of the disastrous
      2002 Rodeo-Chediski fire. Social tensions between locals and amenity migrants
      temporarily dissolved immediately following the disaster, only to be exacerbated
      by the heightened perception of risk and the differential commitment to hazard
      mitigation displayed by these groups over a 2-year study period. Findings suggest
      that to enhance wildfire safety, environmental managers should acknowledge the
      environmental benefits associated with hazardous landscapes, the incentives
      created by risk management programs, and the specific constraints to action for
      relevant social groups in changing human-environmental context.

PMID- 19597871
TI  - Stream discharge and riparian land use influence in-stream concentrations and
      loads of phosphorus from central plains watersheds.
AB  - Total annual nutrient loads are a function of both watershed characteristics and
      the magnitude of nutrient mobilizing events. We investigated linkages among land
      cover, discharge and total phosphorus (TP) concentrations, and loads in 25 Kansas
      streams. Stream monitoring locations were selected from the Kansas Department of
      Health and Environment stream chemistry long-term monitoring network sites at or
      near U.S. Geological Survey stream gauges. We linked each sample with concurrent
      discharge data to improve our ability to estimate TP concentrations and loads
      across the full range of possible flow conditions. Median TP concentration was
      strongly linked (R (2) = 76%) to the presence of cropland in the riparian zones
      of the mostly perennial streams. At baseflow, discharge data did not improve
      prediction of TP, but at high flows discharge was strongly linked to
      concentration (a threshold response occurred). Our data suggest that on average
      88% of the total load occurred during the 10% of the time with the greatest
      discharge. Modeled reductions in peak discharges, representing increased
      hydrologic retention, predicted greater decreases in total annual loads than
      reductions of ambient concentrations because high discharge and elevated
      phosphorus concentrations had multiplicative effects. No measure of land use
      provided significant predictive power for concentrations when discharge was
      elevated or for concentration rise rates under increasing discharge. These
      results suggest that reductions of baseflow concentrations of TP in streams
      without wastewater dischargers may be managed by reductions of cropland uses in
      the riparian corridor. Additional measures may be needed to manage TP annual
      loads, due to the large percentage of the TP load occurring during a few high
      flow events each year.

PMID- 19597872
TI  - Long-term effects of changing land use practices on surface water quality in a
      coastal river and lagoonal estuary.
AB  - The watershed of the Neuse River, a major tributary of the largest lagoonal
      estuary on the U.S. mainland, has sustained rapid growth of human and swine
      populations. This study integrated a decade of available land cover and water
      quality data to examine relationships between land use changes and surface water
      quality. Geographic Information Systems (GIS) analysis was used to characterize
      26 subbasins throughout the watershed for changes in land use during 1992-2001,
      considering urban, agricultural (cropland, animal as pasture, and densities of
      confined animal feed operations [CAFOs]), forested, grassland, and wetland
      categories and numbers of wastewater treatment plants (WWTPs). GIS was also used
      together with longitudinal regression analysis to identify specific land use
      characteristics that influenced surface water quality. Total phosphorus
      concentrations were significantly higher during summer in subbasins with high
      densities of WWTPs and CAFOs. Nitrate was significantly higher during winter in
      subbasins with high numbers of WWTPs, and organic nitrogen was higher in
      subbasins with higher agricultural coverage, especially with high coverage of
      pastures fertilized with animal manure. Ammonium concentrations were elevated
      after high precipitation. Overall, wastewater discharges in the upper,
      increasingly urbanized Neuse basin and intensive swine agriculture in the lower
      basin have been the highest contributors of nitrogen and phosphorus to receiving
      surface waters. Although nonpoint sources have been emphasized in the
      eutrophication of rivers and estuaries such as the Neuse, point sources continue
      to be major nutrient contributors in watersheds sustaining increasing human
      population growth. The described correlation and regression analyses represent a
      rapid, reliable method to relate land use patterns to water quality, and they can
      be adapted to watersheds in any region.

PMID- 19597873
TI  - Climate change and river ecosystems: protection and adaptation options.
AB  - Rivers provide a special suite of goods and services valued highly by the public
      that are inextricably linked to their flow dynamics and the interaction of flow
      with the landscape. Yet most rivers are within watersheds that are stressed to
      some extent by human activities including development, dams, or extractive uses.
      Climate change will add to and magnify risks that are already present through its
      potential to alter rainfall, temperature, runoff patterns, and to disrupt
      biological communities and sever ecological linkages. We provide an overview of
      the predicted impacts based on published studies to date, discuss both reactive
      and proactive management responses, and outline six categories of management
      actions that will contribute substantially to the protection of valuable river
      assets. To be effective, management must be place-based focusing on local
      watershed scales that are most relevant to management scales. The first priority
      should be enhancing environmental monitoring of changes and river responses
      coupled with the development of local scenario-building exercises that take land
      use and water use into account. Protection of a greater number of rivers and
      riparian corridors is essential, as is conjunctive groundwater/surface water
      management. This will require collaborations among multiple partners in the
      respective river basins and wise land use planning to minimize additional
      development in watersheds with valued rivers. Ensuring environmental flows by
      purchasing or leasing water rights and/or altering reservoir release patterns
      will be needed for many rivers. Implementing restoration projects proactively can
      be used to protect existing resources so that expensive reactive restoration to
      repair damage associated with a changing climate is minimized. Special attention
      should be given to diversifying and replicating habitats of special importance
      and to monitoring populations at high risk or of special value so that management
      interventions can occur if the risks to habitats or species increase
      significantly over time.

PMID- 19597874
TI  - Surgical management of infected pseudoaneurysms in intravenous drug abusers:
      single institution experience and a proposed algorithm.
AB  - BACKGROUND: Vascular complications from intravenous drug abuse pose significant
      challenges to vascular surgeons. No formalized policies have been reached on
      surgical management of the resultant infected pseudoaneurysm. METHODS: A
      retrospective review of all patients who underwent surgery for pseudoaneurysms
      due to chronic intravenous drug abuse from July 2005 to February 2008 was
      performed. RESULTS: A total of 15 patients with infected pseudoaneurysms from
      chronic intravenous drug abuse were operated on during the study period. The
      sites of involvement were restricted to the femoral (86.7%) and brachial (13.3%)
      areas. The drug involved was buprenorphine (Subutex) in all cases. Pain over the
      limb swelling (100%), pulsatility (60%), and symptoms suggestive of septicemia
      (46.7%) were the most common symptoms. Staphylococcus aureus was present in
      93.3%. Diagnosis was achieved clinically in 26.7%, by duplex ultrasonography in
      60.0%, and by computed tomography (CT) angiography in 13.3%. In the two patients
      with brachial pseudoaneurysms, the brachial artery was ligated in one, and a
      basilic vein patch was used in the other. In the 13 patients with femoral
      pseudoaneurysms, the pseudoaneurysm was ligated and excised in 8 (61.5%), and
      immediate reconstructive bypass surgery was performed in 5 (38.5%). Two patients
      had critical ischemia after ligation and required reconstructive bypass surgery a
      few weeks later. Postoperative complications included claudication, digital
      gangrene, localized wound infection, and rebleeding. There was no associated
      mortality. CONCLUSIONS: Pseudoaneurysm from intravenous drug abuse continues to
      pose significant challenges to surgeons worldwide, ranging from an accurate
      diagnosis to the choice of surgery. The aims of surgery must be to achieve
      adequate debridement and control infection and hemorrhage. Any associated
      postoperative complications must be identified and dealt with.

PMID- 19597876
TI  - Technique of antroduodenectomy without ulcer excision as a safe alternative
      treatment for bleeding chronic duodenal ulcers.

PMID- 19597875
TI  - Technical standardization of laparoscopic herniorraphy in pediatric patients.
AB  - BACKGROUND: Laparoscopic inguinal hernia repair is rarely reported in pediatric
      patients. We report our experience on this topic to show the standardization of
      the technique. METHODS: In a 3-year period we operated 315 patients for
      unilateral inguinal hernia using laparoscopy. Fifty of the 315 patients (15.9%)
      were younger than 1 year old. The age ranged from 1 month to 8 years (median 3.2)
      with a median body weight of 14.3 kg. We always used three trocars, and we used
      the modified laparoscopic herniorraphy according to Montupet. After sectioning
      the sac distally to the ring, the periorificial peritoneum was closed with a
      purse-string suture of nonresorbable suture material. RESULTS: The operating time
      averaged 25 min. All the procedures were performed in a day-hospital setting. In
      123/315 patients (39%), at operation we found a contralateral patency of the
      processus vaginalis. In these 123 cases we performed a bilateral herniorraphy. In
      one girl (0.3%) we found a coexistence of oblique external hernia and a direct
      hernia, and both orifices were sutured in laparoscopy. We recorded only 1 minor
      complication: a problem with needle extraction. With a minimum follow-up of 1
      year, there were 2 recurrences (0.6%). CONCLUSIONS: We believe that laparoscopic
      repair of inguinal hernia in expert hands is a safe and effective procedure. It
      makes it possible to repair all forms of inguinal hernia simultaneously, together
      with contralateral patencies, which has cemented its role as an alternative to
      conventional repair.

PMID- 19597877
TI  - Epidemiology of injuries at a tertiary care center in Malawi.
AB  - BACKGROUND: Injury surveillance is an ongoing process required for primary,
      secondary, and tertiary injury prevention. In Malawi, hospital-based injury data
      are not available. METHODS: From February to June 2008 we collected data on
      injured patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi. The
      sample (n = 1,474) was predominantly male (75.7%), and age distribution was
      bimodal (peak age groups <5 years and 26-30 years). Road-traffic injury (RTI) was
      the most common reason for treatment (43.4%), followed by assault (24.0%), which
      was more common than expected. The most common injuries were lacerations,
      contusions, and abrasions. We observed both gender- and age-specific patterns in
      injury mechanism: Injured females were more likely than injured males to have
      suffered an injury as a passenger in a car or on a bicycle, or to have suffered
      from falls, foreign bodies, and burns; injured males were more likely than
      injured females to have suffered an injury as an automobile driver or bicyclist,
      or from an assault. Falls, burns, and foreign bodies affected younger victims,
      whereas bicyclists, automobile drivers, and motorcycle operators were generally
      older persons. RESULTS: The hospital admission rate was 26.8%. Most patients
      arrived by private vehicle (43.8%), which was also the fastest means of
      transportation. There were 25 mass casualties leading to 102 admissions; all but
      one were due to RTIs, and seven were associated with at least one fatality.
      CONCLUSIONS: This study elucidated injury epidemiology in Malawi and identified
      questions for future research. Other developing countries should conduct such
      prospective data collection to identify region-specific injury patterns and to
      promote injury prevention.

PMID- 19597879
TI  - Stabilized infective endocarditis and altered heparin responsiveness during
      cardiopulmonary bypass.
AB  - BACKGROUND: Although active infective endocarditis (IE) is known as a risk factor
      for decreased heparin responsiveness during cardiopulmonary bypass (CPB),
      evidence is lacking in patients with stabilized IE. We investigated whether
      heparin responsiveness was still altered in stabilized IE patients undergoing
      cardiac surgery in a prospective, controlled trial. METHODS: A total of 16
      patients with stabilized IE without signs of active inflammation (IE group) and
      48 patients without systemic infection (control group) undergoing valve surgery
      were included. Heparin responsiveness was assessed using the heparin sensitivity
      index (HSI), whereas heparin resistance was defined as an activated clotting time
      (ACT) occurring less than 400 s after the initial heparinization. RESULTS:
      Preoperative antithrombin III activity was lower and fibrinogen level was higher
      in the IE group. ACT after initial heparinization was shorter in the IE group.
      The HSI was lower and the number of patients with HSI <1.0 was greater in the IE
      group. Heparin resistance occurred more frequently in the IE group. CONCLUSIONS:
      Heparin responsiveness during CPB was significantly reduced in the IE group, and
      it seems to be associated with preoperative hypercoagulability and reduced
      antithrombin III activity. Therapeutic measures such as the administration of
      antithrombin III concentrate should be considered in these patients even when
      they are in a stabilized condition without active inflammation.

PMID- 19597880
TI  - Broken esophageal stent successfully treated by interventional radiology
      technique.
AB  - Esophageal stent fractures occur quite rarely. A 61-year-old male patient was
      previously treated for rupture of benign stenosis, occurring after dilatation, by
      implanting an esophageal stent. However, a year after implantation, the patient
      suffered from dysphagia caused by the broken esophageal stent. He was treated
      with the interventional radiology technique, whereby a second implantation of the
      esophageal stent was carried out quite successfully.

PMID- 19597878
TI  - Three-port versus four-port laparoscopic cholecystectomy: meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: Since the first laparoscopic cholecystectomy was reported, the four
      trocar laparoscope has become the golden standard procedure. Some surgeons,
      however, thought that the three-port technique may be safe, effective, and
      economic. Our meta-analysis compared the three-port technique to the four-port
      technique. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE, and
      Chinese Biomedical Literature Database. Quality assessment and data extraction
      were done by two reviewers independently. The statistical analysis was performed
      by RevMan4.2.10 software. RESULTS: A total of five publications comprising 591
      patients met the inclusion criteria. The result showed that three-port technique
      could not reduce the analgesia requirements: the sample mean difference (SMD) and
      95% confidence interval (CI) were -0.28 (-0.66, 0.10). There were no significant
      differences between the two groups in terms of operating time [weighted mean
      difference (WMD) = 2.08, 95% CI (-3.63, 7.79)], success rate [odds ratio (OR) =
      0.99,95% CI (0.31, 3.12)], or postoperative hospital stay [OR = -0.52,95% CI (
      1.22, 0.17)]. CONCLUSIONS: The current evidence showed that the two groups had
      similar operating times, success rates, analgesia requirements, and postoperative
      hospital stays. The methodological qualities of studies are not high, so more
      high-quality studies are needed for further analysis.

PMID- 19597881
TI  - Percutaneous ablation of a mesenteric cyst using ethanol: is it feasible?
AB  - A huge mesenteric cyst in a 61-year-old female was treated by percutaneous
      ablation using ethanol. Marked shrinkage was achieved and regrowth was not seen
      16 months after ablation. Resection is the standard therapy for mesenteric cysts,
      but it may be valuable to discuss the feasibility of percutaneous ablation before
      resection if the lesion wall is smooth and thin, and if solid nodules are not
      depicted on imaging.

PMID- 19597882
TI  - Iatrogenic portobiliary fistula treated by stent-graft placement.
AB  - Stent-graft exclusion of an ischemic, hilar portobiliary fistula after liver
      transplantation has not been reported. Isolated reports have described peripheral
      or nonischemic fistulas, and alternative treatment options have ranged from
      balloon tamponade to surgical repair. We present a unique case of a hilar
      portobiliary fistula successfully treated to resolution by unilateral placement
      of a stent-graft.

PMID- 19597883
TI  - Cone-beam computed tomography-guided percutaneous radiologic gastrostomy.
AB  - The purpose of this study was to investigate the feasibility of a flat-detector C
      arm-guided radiographic technique (cone-beam computed tomography [CBCT]) for
      percutaneous radiologic gastrostomy (PRG) insertion. Eighteen patients (13 men
      and 5 women; mean age 62 years) in whom percutaneous endoscopic gastrostomy (PEG)
      had failed underwent CBCT-guided PRG insertion. PEG failure or unsuitability was
      caused by upper gastrointestinal tract obstruction in all cases. Indications for
      gastrostomy were esophageal and head and neck malignancies, respectively. Before
      the PRG procedure, initial C-arm CBCT scans were acquired. Three- and 2
      dimensional soft-tissue reconstructions of the epigastrium region were generated
      on a dedicated workstation. Subsequently, gastropexy was performed with T
      fasteners after CBCT-guided puncture of the stomach bubble, followed by insertion
      of an 14F balloon-retained catheter through a peel-away introducer. Puncture of
      the stomach bubble and PRG insertion was technically successful in all patients
      without alteration of the epigastric region. There was no malpositioning of the
      tube or other major periprocedural complications. In 2 patients, minor
      complications occurred during the first 30 days of follow-up (PRG malfunction: n
      = 1; slight infection: n = 1). Late complications, which were mainly tube
      disturbances, were observed in 2 patients. The mean follow-up time was 212 days.
      CBCT-guided PRG is a safe, well-tolerated, and successful method of gastrostomy
      insertion in patients in whom endoscopic gastrostomy is not feasible. CBCT
      provides detailed imaging of the soft tissue and surrounding structures of the
      epigastric region in one diagnostic tour and thus significantly improves the
      planning of PRG procedures.

PMID- 19597884
TI  - Endovascular management of posttraumatic arteriovenous fistulae.
AB  - Surgery is considered to be the treatment of choice for vascular injuries caused
      by trauma. However, endovascular techniques are emerging as an alternative means
      of treatment. In this article, we describe three patients with posttraumatic
      arteriovenous fistulae in different body regions that were managed using
      endovascular techniques. Each case had its unique set of associated problems
      requiring innovative methods and a multidisciplinary approach. While the short
      term results are encouraging, long-term follow-up of posttraumatic arteriovenous
      fistulae that have been treated with endovascular techniques is still required.

PMID- 19597885
TI  - Benzoate catabolite repression of the phenol degradation in Acinetobacter
      calcoaceticus PHEA-2.
AB  - Acinetobacter calcoaceticus PHEA-2 exhibited a delayed utilization of phenol in
      the presence of benzoate. Benzoate supplementation completely inhibited phenol
      degradation in a benzoate 1,2-dioxygenase knockout mutant. The mphR encoding the
      transcriptional activator and mphN encoding the largest subunit of multi
      component phenol hydroxylase in the benA mutant were significantly downregulated
      (about 7- and 70-fold) on the basis of mRNA levels when benzoate was added to the
      medium. The co-transformant assay of E. coli JM109 with mphK::lacZ fusion and the
      plasmid pETR carrying mphR gene showed that MphR did not activate the mph
      promoter in the presence of benzoate. These results suggest that catabolite
      repression of phenol degradation by benzoate in A. calcoaceticus PHEA-2 is
      mediated by the inhibition of the activator protein MphR.

PMID- 19597890
TI  - Percutaneous CT-guided treatment of lumbar facet joint synovial cysts.
AB  - Symptomatic intraspinal lumbar facet joint synovial cysts can be managed both
      conservatively and surgically. Diagnosis of the lumbar facet joint cyst is made
      through cross-sectional imaging of the spine, either by computerized tomography
      (CT) scan, myelography, or most commonly magnetic resonance imaging. Conservative
      treatment by facet joint injection can be performed under fluoroscopic or CT
      guidance, although only CT guidance provides direct visualization of the cyst
      confirming accurate needle placement. This case report illustrates the use of
      percutaneous CT-guided facet joint cyst treatment as a temporizing measure or
      alternative to surgical treatment in the proper clinical scenario.

PMID- 19597889
TI  - Immediate repair of major abdominal wall defect after extensive tumor excision in
      patients with abdominal wall neoplasm: a retrospective review of 27 cases
      [corrected].
AB  - BACKGROUND: The treatment of abdominal wall neoplasm continues to present a
      challenging problem because it is not easy to repair the giant defect which is
      resulted from extensive tumor excision. Some techniques and materials have been
      reported, but most report a certain technique or material for abdominal wall
      reconstruction. Therefore, we retrospectively reviewed the treatment of such
      patients in our department and assessed the reconstruction algorithm in such a
      situation. METHODS: We studied 27 patients undergoing immediate abdominal wall
      reconstruction between 1999 and 2008 who sought care for major defects after
      extensive tumor excision of malignancy. We categorized the defects into three
      types: type I, defects involving only the loss of skin (15 cases); type II,
      myofascial defects with intact skin coverage (6 cases); and type III, myofascial
      defects without skin coverage (6 cases). Different techniques and materials were
      used. Postoperative morbidities, sign of herniation, and other follow-up data
      were recorded. RESULTS: The immediate abdominal wall reconstruction was
      successful in all patients. There was no severe morbidity after the operation.
      Only one patient developed hernia. CONCLUSIONS: Most type I defects can be
      corrected with primary suture. For type II defects, a prosthetic or biological
      mesh, or alternatively an autologous fascial substitute, may be used. For type
      III defects, the resulting full-thickness defect will require a myocutaneous
      flap, such as the tensor fascia lata flap, with or without a mesh for abdominal
      wall reconstruction. Human acellular dermal matrix, a biological mesh, is an
      ideal alternative for synthetic mesh, especially in situations of infection or
      contamination.

PMID- 19597886
TI  - Allelic imbalance at p53 and microsatellite instability are predictive markers
      for resistance to chemotherapy in gastric carcinoma.
AB  - BACKGROUND: Combined treatment with 5-fluorouracil and cisplatin (FP
      chemotherapy) is an effective neoadjuvant regimen for gastric carcinoma. However,
      it is ineffective in half of all patients. This study tests the hypothesis that
      genetic markers might identify those patients with gastric cancer who would
      respond to neoadjuvant FP chemotherapy. MATERIALS AND METHODS: A total of 23
      patients with gastric carcinoma were treated with neoadjuvant chemotherapy.
      Pretreatment biopsy specimens before neoadjuvant chemotherapy were obtained from
      15 of 23 patients, and resected tumors were obtained from all 23. Genetic studies
      were performed to detect allelic imbalance (AI), microsatellite instability
      (MSI), and K-ras mutation. RESULTS: A clinical response was observed in 13 of 23
      patients. Kaplan-Meier survival curve showed that clinical responder group had a
      significantly higher likelihood of overall survival (P = 0.0165), compared with
      nonresponder group. In 23 resection specimens, 10 of 23 tumors presented AI at
      the p53 locus and/or MSI; 8 of the 10 tumors were nonresponders, while 12 of 13
      tumors without p53 AI or MSI were responders (P = 0.0007). In 15 pretreatment
      biopsy specimens, 8 tumors had p53 AI and/or MSI; 7 of the 8 tumors were
      nonresponders, while 6 of 7 tumors without p53 AI or MSI were responders to
      preoperative chemotherapy (P = 0.008). Tumors with AI at the p53 locus and/or MSI
      were significantly more resistant to neoadjuvant chemotherapy. No relationship
      was found between K-ras mutations and responses. CONCLUSIONS: Analysis for p53 AI
      and MSI might represent a clinically useful approach to predicting the response
      to neoadjuvant FP chemotherapy in gastric carcinoma.

PMID- 19597892
TI  - Predictors of outcome after exacerbation of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The outcome after hospitalization for an exacerbation of chronic
      obstructive pulmonary disease (COPD) is unfavorable and uncertainty exists about
      factors predicting short and long-term prognosis. OBJECTIVE: To identify clinical
      predictors of length of hospital stay (LOS) and three-year mortality after COPD
      exacerbations requiring hospitalization. DESIGN: Retrospective analysis of
      prospectively collected data. PARTICIPANTS AND METHODS: All consecutive patients
      hospitalized with COPD exacerbation were enrolled. Disease severity was estimated
      by FEV(1,) body mass index (BMI), Medical Research Council (MRC) chronic dyspnoea
      scale, previous hospitalizations, need for long-term oxygen treatment (LTOT),
      arterial oxygen and carbon dioxide partial pressures (PaO(2) and PaCO(2)), pH and
      respiratory rate. Outcome was assessed by LOS and three-year mortality. MAIN
      RESULTS: Out of 81 patients enrolled, three-year mortality data were available
      for 61. LOS was related to BMI, MRC scale and respiratory rate. Three-year
      mortality was related to FEV(1), BMI, MRC scale, LTOT, and PaCO(2). Multiple
      logistic regression analysis demonstrated that MRC scale was the only independent
      determinant of LOS, [p = 0.001, odds ratio (OR) 7.67 (95% CI 2.50-23.41)],
      whereas MRC scale and BMI predicted three-year mortality, [p = 0.001, OR 8.28
      (95% CI 2.25-30.47) and p = 0.006, OR 6.91 (95% CI 1.74-27.48), respectively].
      Cox regression analysis demonstrated identical results. Using receiver-operator
      optimized thresholds for these variables (MRC > 2 and BMI < 25 kg/m(2)), we
      propose a prediction model that accurately determines three-year mortality risk.
      CONCLUSIONS: In this study, MRC scale and BMI predicted outcome after COPD
      hospitalization. Pending further validation, this predictive model may contribute
      to identify patients with poor outcome even when spirometric data are
      unavailable.

PMID- 19597894
TI  - Aligning physician and hospital incentives: the approach at hospital for special
      surgery.
AB  - Healthcare administrators and physicians alike are navigating an increasingly
      complex and highly regulated healthcare environment. Unlike in the past,
      institutions now require strong collaboration among physician and administrative
      leaders. As providers and managers are trained and work differently, new methods
      are needed to provide the infrastructure and resources necessary to create,
      nurture, and sustain alignment between them. We describe four initiatives by
      administrators and physicians at Hospital for Special Surgery to work together in
      mutually beneficial relationships that help us achieve the highest level of
      patient care, satisfaction and safety. These initiatives include improving
      management efficiency through an orthopaedic service line structure, helping
      individual physicians grow their practices through the demand-office-operating
      room initiative of the Physicians Service Department, controlling costs through
      the supply effectiveness policy, and promoting teamwork in innovation through the
      technology transfer program.

PMID- 19597893
TI  - The role of primary care physicians in cancer care.
AB  - BACKGROUND: The demand for oncology services in the United States (US) is
      increasing, whereas a shortage of oncologists looms. There is the need for a
      better understanding of the involvement of primary care physicians (PCPs) in
      cancer care. OBJECTIVE: To characterize the role of PCPs in cancer care, compare
      it with that of oncologists, and identify factors explaining greater PCP
      involvement in cancer care. DESIGN: National survey of physicians caring for
      cancer patients conducted by the Cancer Care Outcomes Research and Surveillance
      Consortium. PARTICIPANTS: 1694 PCPs; 1621 oncologists. MEASUREMENTS:
      Questionnaires mailed during 2005 and 2006 examined the participation of
      physicians in 12 aspects of care for cancer patients. MAIN RESULTS: Over 90% of
      PCPs fulfilled general medical care roles for patients with cancer such as
      managing comorbid conditions, chronic pain, or depression; establishing do-not
      resuscitate status; and referring patients to hospice. Oncologists were less
      involved in these roles. Determining the treatment preferences of individual
      patients and deciding on the use of surgery were the only cancer care roles in
      which > or =50% of PCPs participated. Twenty-two percent of PCPs reported no
      direct involvement in cancer care roles while 19% reported heavy involvement.
      PCPs who were aged > or =50 years, were internists or geriatricians, taught
      medical students, saw more cancer patients, or experienced referral barriers
      fulfilled more roles. Rural practice location was not associated with greater PCP
      involvement in cancer care. CONCLUSIONS: PCPs across the US have an active role
      in cancer patient management. Determining the optimal interface between PCPs and
      oncologists in delivering and coordinating cancer care is an important area for
      future research.

PMID- 19597895
TI  - Levels of expression for BMP-7 and several BMP antagonists may play an integral
      role in a fracture nonunion: a pilot study.
AB  - Delays in bone healing or even the development of a nonunion could be related to
      the concentrations and/or functions of the bone morphogenetic proteins (BMPs).
      The RNA expression profile of the BMPs within fracture nonunion tissue is
      unknown. This preliminary descriptive study was performed to define the RNA
      profiles of the BMPs, their receptors, and their inhibitors within human fracture
      nonunion tissue and correlate them to matched healing bone. All patients had
      hypertrophic nonunions. Tissue samples taken from the nonunion site of 15
      patients undergoing surgical treatment for an established nonunion were analyzed.
      The RNA expression patterns of BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8; BMP
      receptor Types IA, IB, and II; and the BMP inhibitors chordin, Noggin, Drm
      (Gremlin), and follistatin were determined in the nonunion (fibrous tissue) and
      healing bone (callus tissue) using quantitative real-time PCR. Comparison between
      the nonunion and healing bone samples revealed substantially elevated
      concentrations of BMP-4, Drm/Gremlin, follistatin, and Noggin in nonunion tissue
      when compared to healing bone. In contrast, BMP-7 concentration was higher in the
      healing bone. Our data suggest inhibition of BMP-7, by Drm (Gremlin),
      follistatin, and Noggin and upregulation of BMP-4 may play an integral role in
      the development of nonunions.

PMID- 19597896
TI  - Association of osteonecrosis and failure of hip resurfacing arthroplasty.
AB  - Osteonecrosis (ON) has been reported in femoral remnants removed after failure of
      hip resurfacing arthroplasty. Experimental and clinical studies have further
      described thermal effects of the cementation technique, damage of extraosseous
      blood vessels, and intraoperative hypoxemia as possible causative factors. We
      analyzed histologically a series of 123 retrieved specimens with a preoperative
      diagnosis other than ON to investigate the incidence and extent of advanced ON.
      ON was found in 88% of cases and associated with 60% (51 of a total of 85) of
      periprosthetic fractures. The fracture incidence correlated with the extent of
      ON. Collapse of necrotic tissue in three (2%) cases resulted in disconnection of
      the bone stock-femoral component. We observed smaller regions of superficial ON
      in the majority of the remaining femoral remnants with periprosthetic fractures
      and in hips that failed for reasons other than fracture.

PMID- 19597897
TI  - Asymmetry in quadriceps rate of force development as a functional outcome measure
      in TKA.
AB  - Quadriceps muscle strength is an important predictor of functional abilities in
      patients having TKA. However, because several daily activities are characterized
      by a limited time to generate force, it has been suggested that rate of force
      development (RFD) could better predict functional difficulties than maximal
      strength. We therefore hypothesized the side-to-side asymmetry would be larger
      for RFD than for maximal strength, and RFD asymmetry relates to subjective
      symptoms and/or functional daily living activities. We studied 31 subjects (17
      women, 14 men) 6 +/- 1 months after undergoing TKA for unilateral osteoarthritis.
      Symptoms and limitations during activities of daily living were quantified using
      the knee outcome survey-activities of daily living scale (KOS-ADLS). Quadriceps
      maximal strength and RFD at different times (50 to 200 ms from contraction onset)
      were quantified during unilateral maximal voluntary isometric actions. Side-to
      side asymmetries (involved versus uninvolved side) were larger for RFD
      (approximately 36%) than for maximal strength (approximately 24%). Subjective
      knee function related to all RFD asymmetry variables, but not to maximal strength
      asymmetry. In addition to maximal strength, quadriceps RFD in the first 100 to
      200 ms from contraction onset provides an alternative functional outcome measure
      for individuals undergoing TKA.

PMID- 19597898
TI  - Does bearing design influence midterm survivorship of unicompartmental
      arthroplasty?
AB  - Medial unicompartmental arthroplasties (UKA) are available with mobile- and fixed
      bearing designs, with the advantages of one bearing over another unproven. We
      questioned whether the bearing design influenced clinical outcome, survivorship,
      the reason for revision, or the timing of failures. We retrospectively reviewed
      179 patients (229 knees) who had medial unicompartmental knee arthroplasties
      between 1990 and 2007; of these 79 knees had a mobile-bearing design and 150
      knees a fixed-bearing design. Patients with mobile-bearing UKA had a minimum
      followup of 1 year (mean, 3.6 years; range, 1-11.3 years); those with fixed
      bearing UKA a minimum followup of 1 year (mean, 8.1 years; range, 1-17.8 years).
      Patients were evaluated with clinical outcome scores and radiographically using
      the Knee Society rating system. Seven of 79 (9%) mobile-bearing knees underwent
      revision at a mean of 2.6 years, and 22 of 150 (15%) fixed-bearing knees
      underwent revision at a mean of 6.9 years. The 5-year cumulative survival rates
      were 88% (SE +/- 0.47, 95% CI 0.7229-1) and 96% (SE +/- 0.16, 95% CI 0.93-0.9979)
      for the mobile- and fixed-bearing designs respectively using the endpoint of
      revision surgery. We observed no differences in the indications or complexity of
      revision surgery between the groups and none in midterm survivorship. LEVEL OF
      EVIDENCE: Level III, comparative study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19597899
TI  - Should one consider primary surgical reconstruction in charcot arthropathy of the
      feet?
AB  - Charcot neuroosteoarthropathy of the feet can induce severe instability and
      deformity with subsequent plantar ulceration leading to substantial disability or
      even amputation. Traditionally, nonoperative treatment is regarded as the primary
      option of treatment while surgery is restricted to treating complications or
      failure of nonoperative treatment. Failed nonoperative treatment essentially
      prolongs treatment period. We retrospectively reviewed 22 patients (26 feet) with
      midfoot (n = 9) or hindfoot (n = 17) neuropathy who underwent primary surgical
      reconstruction and reorientation arthrodesis due to manifest instability,
      nonplantigrade foot position, and deformity with overt (n = 8) or what we judged
      was impending ulceration (n = 9). The minimum followup was 0.5 years (mean, 2.7
      years; range 0.5-7 years). All eight ulcers healed without recurrence of
      ulceration or manifestation of new ulcers during the followup period. We observed
      complications leading to further surgery in nine patients: five with
      perioperative hematoma and four with instability. AOFAS scores rose from a
      preoperative mean of 39 to 70 points (hindfoot cases) and from 51 points to 84
      (midfoot cases). Early surgical reconstruction in high-risk patients can provide
      timely restoration of a plantigrade and stable foot and improved quality of life
      of the patient at complication rates comparable to those after secondary surgery
      following failed nonoperative treatment; however we emphasize we had no control
      group in this small case series for which we could compare nonoperative
      treatment. LEVEL OF EVIDENCE: Level IV, therapeutic study (case series). See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 19597900
TI  - Metastatic giant cell tumor of bone: are there associated factors and best
      treatment modalities?
AB  - Giant cell tumors of bone are sometimes locally aggressive and may metastasize,
      although uncommonly. We attempted to identify associations of clinical and
      histopathologic parameters with metastasis, the long-term outcome with
      metastases, and the best treatment. We identified distant metastases in 24 of 470
      patients with giant cell tumors during a 20-year period. The median age of these
      24 patients at presentation was 26 years (range, 16-76 years), and the
      male:female ratio was 1.6:1, with no predilection for primary site. Metastasis
      occurred at a mean of 2 years (range, 4 months-11 years) after initial diagnosis.
      Sites for distant metastases were the lung (21 of 24 patients), scalp, calf
      muscle, and regional lymph nodes. The 24 patients had a mean followup of 3.5
      years (range, 0-16 years). Thirteen of the 24 patients has local recurrence
      before or at the time of metastasis. Two patients refused treatment, eight
      underwent metastasectomy, and 14 were inoperable (four had chemotherapy, 10 were
      treated symptomatically). We observed disease progression with hemoptysis in one
      of 14 patients. None of the patients died of their metastatic disease. None of
      the risk factors we studied was associated with metastasis in giant cell tumors.
      Although the overall outcome was favorable, metastasectomy is recommended where
      feasible. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 19597901
TI  - Biopsy of soft tissue masses: evidence-based medicine for the musculoskeletal
      tumor society.
AB  - The literature contains a number of controversies regarding key questions: (1)
      When is a biopsy indicated? (2) How should the biopsy be placed? (3) How should
      the biopsy be performed and which has the greatest diagnostic accuracy? (4) Who
      should perform the biopsy? (5) What clinical parameters present the greatest
      diagnostic difficulty? Using PubMed and Google Scholar we performed English
      language literature searches of clinical studies reporting biopsy of soft tissue
      masses. Thirty-two studies met the inclusion criteria but were only able to
      address three of the five questions the authors had hoped to evaluate. Available
      evidence suggests open biopsy has the highest diagnostic accuracy over core
      needle biopsy, which was higher than fine needle aspiration. There was no
      evidence to address who is best suited to perform the biopsy (general surgeon,
      orthopaedic surgeon, radiologist, pathologist) in terms of accuracy of diagnosis.
      Frozen section at the time of biopsy may improve diagnostic accuracy. Diagnostic
      difficulty was associated with myxoid and round cell neoplasms, infections, and
      tumors located in the paraspinal region. The limited number of references
      addressing these issues demonstrated the need for more Level I research in the
      area of biopsy of soft tissue masses. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19597903
TI  - Lentiviral-mediated transgene expression can potentiate intestinal mesenchymal
      epithelial signaling.
AB  - Mesenchymal-epithelial signaling is essential for the development of many organs
      and is often disrupted in disease. In this study, we demonstrate the use of
      lentiviral-mediated transgene delivery as an effective approach for ectopic
      transgene expression and an alternative to generation of transgenic animals. One
      benefit to this approach is that it can be used independently or in conjunction
      with established transgenic or knockout animals for studying modulation of
      mesenchymal-epithelial interactions. To display the power of this approach, we
      explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme
      and demonstrate its functional influence on the adjacent epithelium. Our findings
      highlight the efficient use of lentiviral-mediated transgene expression for
      modulating mesenchymal-epithelial interactions in vivo.

PMID- 19597904
TI  - Segmentation of extrapulmonary tuberculosis infection using modified automatic
      seeded region growing.
AB  - In the image segmentation process of positron emission tomography combined with
      computed tomography (PET/CT) imaging, previous works used information in CT only
      for segmenting the image without utilizing the information that can be provided
      by PET. This paper proposes to utilize the hot spot values in PET to guide the
      segmentation in CT, in automatic image segmentation using seeded region growing
      (SRG) technique. This automatic segmentation routine can be used as part of
      automatic diagnostic tools. In addition to the original initial seed selection
      using hot spot values in PET, this paper also introduces a new SRG growing
      criterion, the sliding windows. Fourteen images of patients having extrapulmonary
      tuberculosis have been examined using the above-mentioned method. To evaluate the
      performance of the modified SRG, three fidelity criteria are measured: percentage
      of under-segmentation area, percentage of over-segmentation area, and average
      time consumption. In terms of the under-segmentation percentage, SRG with average
      of the region growing criterion shows the least error percentage (51.85%).
      Meanwhile, SRG with local averaging and variance yielded the best results (2.67%)
      for the over-segmentation percentage. In terms of the time complexity, the
      modified SRG with local averaging and variance growing criterion shows the best
      performance with 5.273 s average execution time. The results indicate that the
      proposed methods yield fairly good performance in terms of the over- and under
      segmentation area. The results also demonstrated that the hot spot values in PET
      can be used to guide the automatic segmentation in CT image.

PMID- 19597902
TI  - Biapigenin modulates the activity of the adenine nucleotide translocator in
      isolated rat brain mitochondria.
AB  - In this study, we investigated the effects of biapigenin, a biflavone present in
      the extracts of Hypericum perforatum, in rat brain mitochondrial bioenergetics
      and calcium homeostasis. We found that biapigenin significantly decreased
      adenosine diphosphate (ADP)-induced membrane depolarization and increased
      repolarization (by 68 and 37%, respectively). These effects were blocked by
      atractyloside and bongkrekic acid, but not oligomycin. In the presence of
      biapigenin, an ADP-stimulated state 3 respiration was still noticeable, which did
      not happen in the presence of adenine nucleotide translocator (ANT) inhibitors.
      Taking in consideration the relevance of the ANT in the modulation of the
      mitochondrial permeability transition pore (mPTP), mitochondrial calcium
      homeostasis was evaluated alone or in the presence of biapigenin. We found that
      biapigenin reduces mitochondrial calcium retention by increasing calcium efflux,
      an effect that was blocked by ADP plus oligomycin, an efficient blocker of the
      mPTP in brain mitochondria. Taken together, the results in this article suggest
      that biapigenin modulates mPTP opening, possibly by modulating ANT function,
      contributing for enhanced mitochondrial calcium efflux, thereby reducing calcium
      burden and contributing for neuroprotection against excitotoxicity.

PMID- 19597905
TI  - Height loss in elderly women is preceded by osteoporosis and is associated with
      digestive problems and urinary incontinence.
AB  - SUMMARY: This study explores risk factors for height loss and consequences in
      terms of health and wellbeing, in older women. Osteoporosis, low body-mass index,
      being born in Europe and using medications for both sleep and anxiety were risk
      factors for height loss. Height loss was associated with digestive problems;
      excessive height loss was also associated with urinary stress-incontinence and a
      decline in self-rated health. INTRODUCTION: Height loss is associated with
      osteoporosis, but little is known about its consequences. We aimed to examine the
      risk factors for height loss and the symptoms associated with height loss.
      METHODS: Elderly participants of the Australian Longitudinal Study on Women's
      Health (aged 70-75 in 1996) who provided data on height at any two consecutive
      surveys (held in 1996, 1999, 2002, and 2005) were included (N = 9,852). A
      regression model was fitted with height loss as the outcome and
      sociodemographics, osteoporosis, and other risk factors as explanatory variables.
      Symptoms related to postural changes or raised intra-abdominal pressure were
      analyzed using height loss as an explanatory variable. RESULTS: Over 9 years,
      average height loss per year was -0.12% (95% confidence intervals [95% CI] = 
      0.13 to -0.12) of height at baseline. Height loss was greater among those with
      osteoporosis and low body mass index and those taking medications for sleep and
      anxiety. After adjusting for confounders, symptoms associated with height loss of
      > or =2% were heartburn/indigestion (odds ratio [OR] = 1.19, 95% CI = 1.01 to
      1.40), constipation (OR = 1.18, 95% CI = 1.01 to 1.37), and urinary stress
      incontinence (OR = 1.20, 95% CI = 1.02 to 1.41). CONCLUSION: These findings
      highlight the importance of monitoring height among the elderly in general
      practice and targeting associated symptoms.

PMID- 19597906
TI  - Comment on review by Nordin: "the effect of calcium supplementation on bone loss
      in 32 controlled trials in postmenopausal women".

PMID- 19597907
TI  - Risk factors for hip fracture in older adults: a case-control study in Taiwan.
AB  - We conducted a matched case-control study of hip fracture in older adults. Our
      findings suggest that hip fracture risk was determined by multiple factors. Older
      women characterized by low consumption of milk, peak flow rate, grip strength,
      and bone mineral density (BMD) had increased risk of hip fracture. Older men with
      impaired cognitive function and low BMD were also at higher risk of hip fracture.
      INTRODUCTION: Multiple factors contribute to low-trauma hip fracture in older
      adults. The aim of this study was to determine important characteristics of hip
      fracture in older population. METHODS: A total of 228 patients with first low
      trauma hip fracture were matched with 497 controls. All 77 potential risk factors
      of hip fracture organized into 13 groups were analyzed using conditional logistic
      regression. RESULTS: Low milk intake, peak flow rate, hand grip strength, and
      bone mineral density in women and low mini-mental state examination score and
      bone mineral density in men were further identified to be independently
      associated with elevated hip fracture risk. CONCLUSIONS: The factors found in our
      study may help understand the etiology of hip fracture and be further adopted to
      evaluate the risk of hip fracture in community and clinical setting.

PMID- 19597908
TI  - A survey of bone mineral density of healthy Han adults in China.
AB  - A recent survey of bone mineral density (BMD) in China recruited 7,042 healthy
      Han Chinese aged 20 years and older. The mean BMDs were different in gender, age,
      and region; the proportions of men and women older than 50 years with a high risk
      of osteoporosis were estimated as 10.4% and 31.2%, respectively INTRODUCTION: A
      survey of BMD was completed during 2002-2006 in China. By three-stage sampling, a
      total of 7,042 healthy Han Chinese aged 20 years and older were recruited in ten
      cities: 2,694 subjects from Beijing, Tianjin, Haerbin, Lanzhou, and Yantai of
      northern China and 4,348 from Shanghai, Changsha, Chengdu, Haikou, and Foshan of
      southern China. METHODS: Two dual X-ray absorptiometry (DXA) systems (Hologic and
      Lunar) were used with parallel measurements of the European spine phantoms in
      each center. The mean BMDs in age groups older than 50 and the peak bone mineral
      density (pBMD) at femoral neck and that at greater trochanter were higher for men
      than women, and the pBMDs for northern China were higher than those for southern
      China, ranging from 1% to 4%. DISCUSSION AND CONCLUSION: This work has provided
      two useful references for the first time: one is the estimation of the proportion
      and number of individuals older than 50 years with a high risk of osteoporosis,
      10.4% and 12.5 million men, 31.2% and 37.2 million women, which is important for
      health care planning and marketing projections, and another is the conversion
      equations for cross-calibration among different types of DXA instruments
      frequently used in China.

PMID- 19597909
TI  - Association of TWIST1 gene polymorphisms with bone mineral density in
      postmenopausal women.
AB  - A novel polymorphism (+1871A>G) in the 3' flanking region and haplotypes were
      significantly associated with reduced osteoporosis risk and enhanced bone mineral
      density (BMD). These results suggest that TWIST1 may be a useful genetic marker
      for osteoporosis. Our results provide preliminary evidence supporting an
      association of TWIST1 with osteoporosis in postmenopausal women. INTRODUCTION:
      TWIST1, a basic helix-loop-helix (bHLH) transcription factor, has been implicated
      in cell lineage determination and differentiation. METHODS: To address the
      genetic variations in the TWIST1 gene associated with osteoporosis, we
      investigated the potential involvement of three TWIST1 single-nucleotide
      polymorphisms (SNPs) in osteoporosis in 729 postmenopausal women. BMD was
      measured using dual-energy X-ray absorptiometry. RESULTS: A novel polymorphism in
      the 3' flanking region (+1871A>G) was significantly associated with osteoporosis
      risk (p = 0.007-0.008) and also in multiple comparison (p = 0.02). Consistent
      with these results, haplotype analysis showed that Block1_ht2 had protective
      effects in the dominant and additive model (p = 0.006-0.007). Specifically, the
      +1871A>G polymorphism was overdominantly associated with higher BMD values of the
      femoral neck (p = 0.039). CONCLUSION: These results suggest that TWIST1 may be a
      useful genetic marker for osteoporosis and may have a role on bone metabolism in
      humans. Our results provide preliminary evidence supporting an association of
      TWIST1 with osteoporosis in postmenopausal women.

PMID- 19597911
TI  - Of mice and men: divergent risks of teriparatide-induced osteosarcoma.
AB  - SUMMARY: Since approval by the U.S. Food and Drug Administration (FDA) in
      December 2002, teriparatide (recombinant 1-34 PTH; Forteo) has been safely used
      by more than 430,000 patients. Prior to FDA approval, however, there was concern
      that teriparatide might increase the risk for patients to develop osteosarcoma,
      as almost 45% of the rats treated with this drug at the highest-tested dose level
      developed this aggressive form of bone cancer. Balancing the proven benefits of
      teriparatide shown by clinical trials with the theoretical risk for teriparatide
      induced human osteosarcoma, the FDA mandated both a 'black-box' warning of this
      potential side-effect and a company-sponsored postmarketing surveillance program.
      As a participating institute of that surveillance program, we report upon the
      second person with potential teriparatide-induced osteosarcoma, in this case,
      complicated by a history of pelvic radiation. INTRODUCTION: Given the theoretic
      risk of the drug teriparatide and the known risk of radiation in inducing
      osteosarcoma, we raise the issue of whether teriparatide magnified the risk of
      radiation-induced osteosarcoma in our patient and try to determine which factor
      played the predominant role in the development of his disease. METHODS: We
      analyzed preclinical rat data, human clinical experience with teriparatide, and
      our patient's clinical history to assess the human risk of teriparatide and
      radiation exposure. RESULTS: After the first case of suspected osteosarcoma was
      reported in December 2005, we encountered a second possible teriparatide-induced
      osteosarcoma less than a year later. Review of the preclinical animal data would
      suggest that teriparatide is safe for human use when used as recommended by the
      manufacturer. Given the location of the sarcoma within the field of radiation and
      the limited exposure to teriparatide before diagnosis, it is unlikely that
      teriparatide played the predominant role in the emergence of this patient's
      osteosarcoma. We cannot, however, exclude the possibility that teriparatide
      magnified the carcinogenic effect of radiation therapy to induce the
      osteosarcoma. CONCLUSION: Of more than 430,000 persons who have received
      teriparatide for treatment of severe osteoporosis, we report the second patient
      to develop osteosarcoma. Although teriparatide reduces osteoporosis-related
      fractures in select patient populations, important contraindications, such as
      prior radiation exposure, should be considered before use.

PMID- 19597910
TI  - In osteoporotic women treated with strontium ranelate, strontium is located in
      bone formed during treatment with a maintained degree of mineralization.
AB  - In postmenopausal osteoporotic women and up to 3 years of treatment with
      strontium ranelate, strontium was present only in recently deposited bone tissue
      resulting from formation activity during the period of treatment. Strontium was
      shown to be dose-dependently deposited into this newly formed bone with
      preservation of the mineralization. INTRODUCTION: Interactions between strontium
      (Sr) and bone mineral and its effects on mineralization were investigated in
      women treated with strontium ranelate. METHODS: Bone biopsies from osteoporotic
      women were obtained over 5-year strontium ranelate treatment from phases II and
      III studies. Bone samples obtained over 3-year treatment were investigated by X
      ray microanalysis for bone Sr uptake and focal distribution, and by quantitative
      microradiography for degree of mineralization. On some samples, Sr distribution
      (X-ray cartography) was analyzed on whole sample surfaces and the percentage of
      bone surface containing Sr was calculated. Bone Sr content was chemically
      measured on whole samples. RESULTS: In treated women, Sr was exclusively present
      in bone formed during treatment; Sr deposition depended on the dose with higher
      focal content in new bone structural units than in old ones constantly devoid of
      Sr, even after 3-year treatment. A plateau in global bone Sr content was reached
      after 3 years of treatment. Cartography illustrated the extent of surfaces
      containing Sr, and formation activity during strontium ranelate treatment was
      higher in cancellous than in cortical bone. Mineralization was maintained during
      treatment. CONCLUSION: The quality of bone mineral was preserved after treatment
      with strontium ranelate, supporting the safety of this agent at the bone tissue
      level.

PMID- 19597912
TI  - Estimation of serum osteocalcin and telopeptide-C in postmenopausal osteoporotic
      females.
AB  - A negative correlation of serum C-terminal telopeptide of type I collagen
      (telopeptide-C) was observed with bone mass density (BMD) in postmenopausal
      control (r = -0.70, p < 0.05) and osteoporotic females (r = -0.46, p < 0.05)
      indicating increased bone resorption in these subjects. Since telopeptide-C is a
      significant determinant of bone loss, it can be used, in combination with bone
      mass measurement, for the assessment of postmenopausal females. INTRODUCTION: The
      aim of this study was to find out the significance of serum osteocalcin, a marker
      of bone formation, and C-terminal telopeptide of type I collagen, a marker of
      bone resorption, in evaluating osteoporotic patients and to find out their
      relationship with bone mass density. METHODS: One hundred and fifty (150)
      females; 50 premenopausal (age=31.13 +/- 1.29), 50 postmenopausal (age = 54.36 +/
      0.81) and 50 postmenopausal osteoporotic patients (age = 58.6 +/- 0.701) were
      included in this study. The postmenopausal subjects, with and without
      osteoporosis, were selected from different osteoporotic clinics and healthy
      premenopausal females were selected from general population. Height, weight, BMI,
      waist/hip ratio, age at menarche, years since menopause in case of postmenopausal
      women, history of disease, and fracture, if any, were recorded. BMD assessment
      was done on calcaneous by peripheral ultrasound bone densitometery on Sahara
      Clinical Bone Sonometer and T-scores were calculated. Serum levels of osteocalcin
      and C-terminal telopeptide of type I collagen and calcium were measured. RESULTS:
      A lower BMD in postmenopausal subjects, with and without osteoporosis (p <
      0.001), indicating increased bone loss with aging and menopause, was observed. A
      negative correlation was found between age and BMD (r = -0.67, p < 0.05). No
      correlation was found between osteocalcin and BMD among these groups, suggesting
      heterogeneity of osteocalcin fragments in serum that limits its significance in
      the evaluation of osteoporosis. A positive correlation was found between
      osteocalcin and telopeptide-C (r = 0.26, p < 0.05). A positive correlation of
      telopeptide-C with age (r = 0.45, p < 0.05) and a negative correlation with BMD
      (r = -0.46, p < 0.05) was observed indicating increased bone resorption in
      postmenopausal control and postmenopausal osteoporotic patients. CONCLUSION: C
      terminal telopeptide of type I collagen appears to be a significant determinant
      of bone loss and may be used as a valuable tool in the assessment of
      postmenopausal osteoporotic patients.

PMID- 19597913
TI  - Efficacy and safety of diacerein in early knee osteoarthritis: a randomized
      placebo-controlled trial.
AB  - The objective of this study was to evaluate the efficacy and safety of diacerein
      in early, symptomatic knee osteoarthritis in Indian population. Sixty-four
      patients of knee osteoarthritis fulfilling American College of Rheumatology
      Criteria were randomized to receive either diacerein or placebo for 8 weeks,
      followed by 4 weeks "treatment-free" follow-up in this single-blind, parallel
      group, post-marketing trial. Primary efficacy variable was visual analogue scale
      (VAS) assessment of pain on movement; secondary efficacy variables included
      Western Ontario and Mc Master Universities Osteoarthritis Index (WOMAC) subscores
      for stiffness and physical function, rescue medication use and physician's
      clinical global impression (CGI). Compared to placebo, diacerein showed highly
      significant (p < 0.01) reductions in VAS pain scores, significant (p < 0.05)
      reductions in WOMAC physical function scores, significantly lower requirement for
      rescue medication, and significantly better CGI grades. Incidence of adverse
      events were significantly (p < 0.01) higher in diacerein arm with urine
      discoloration and soft stool being the most common ones. However, most events
      were of mild to moderate intensity. In Indian patients with knee osteoarthritis,
      diacerein effectively reduces pain and improves physical function, and despite
      frequent adverse events, overall tolerability seemed to be good.

PMID- 19597914
TI  - Topical imiquimod in conjunction with Nd:YAG laser for tattoo removal.
AB  - The purpose of this study is to evaluate the efficacy of tattoo removal using
      topical imiquimod 5% cream in conjunction with the 1,064-nm Nd:YAG laser. This
      procedure for tattoo removal will be compared to laser treatment alone, which is
      the standard for cosmetic removal of tattoos. Previous studies have linked
      partial tattoo removal to imiquimod application in a guinea pig model. METHODS:
      This was a small-sized, double-blinded, placebo-controlled trial with patients
      with Fitzpatrick skin types I-IV (light skin) who were 18-65 years of age. The
      patients were required to have had two tattoos of similar age and dark blue or
      black in color in areas that can be covered by clothing. There were four visits
      in total, with laser treatment and photography being performed on the first
      visit. Laser settings were with 1,064-nm Nd:YAG with a 10-ns pulse, 3-mm spot
      size, and 4 J of energy, a standard laser used for tattoo removal. During the
      second visit, tattoos were randomized and chosen to receive either the laser
      imiquimod treatment course or laser-vehicle cream treatment. The patients
      returned 1 month after the completion of cream application (week #10) and 2
      months after the completion of treatment with cream (week #14) for final
      evaluation and photographing. RESULTS: Three patients were enrolled in this
      study. All of them are Fitzpatrick skin type IV. All of the patients were
      compliant with the drug application and have good tolerability with only mild
      pruritus without changing of vascularity or pigmentation. None of the patients
      had ulceration or scar development during the cream application. CONCLUSIONS:
      imiquimod plus laser therapy demonstrated a more favorable outcome when evaluated
      by the investigators or subjects. The mean scores for tattoo clearance from
      baseline to 2 months after completion of treatment with 5% imiquimod cream versus
      placebo cream were 4.3 versus 2.7 as rated by investigators and 4.7 versus 2.3 as
      rated by subjects. No textural changes were observed after therapy and were not
      shown to be different between the two groups. Further large-scale studies are
      important in developing a role for the use of imiqumod in laser-assisted tattoo
      removal.

PMID- 19597915
TI  - Novel predictive tools for Irish radical prostatectomy pathological outcomes:
      development and validation.
AB  - AIMS: We developed and validated prostate cancer predictive models for Irish
      patients, allowing individualised predictions of radical prostatectomy
      pathological outcomes. METHODS: Retrospective review of the Irish Prostate Cancer
      Research Consortium database from 2003 to 2008 was performed. Two predictive
      models were formulated: a replica of the Partin tables (n = 169) and a look-up
      table based on PSA and biopsy Gleason Score (n = 253). Clinico-pathological
      parameters were compared to the Partin data set. Internal validation was
      performed. RESULTS: In total, 70% of patients were at clinical stage T1c. 5.8%
      had a PSA less than 4.1 ng/ml, whereas 25% of the Partin patients had a PSA in
      this range. Maximal predictive accuracy was seen for seminal vesicle invasion
      (area under the curve = 72%). Prediction of extra-prostatic extension and lymph
      node involvement was only equivalent to that of a chance phenomenon. CONCLUSIONS:
      Our current results do not support the introduction of the formulated predictive
      models into routine clinical practice.

PMID- 19597916
TI  - MR imaging features of a retro-odontoid disc herniation.

PMID- 19597918
TI  - The linea arcuata hernia: a report of two cases.
AB  - Two male patients presented to the surgical outpatient clinic with a paramedian
      abdominal bulge. In the first patient, the hardly known diagnosis linea arcuata
      hernia (LAH) had been missed at a previous exploration 8 years ago. In the second
      patient, pre-operative imaging showed an abdominal wall hernia. Diagnostic
      laparoscopy revealed an LAH. In both cases, the hernia was repaired with a mesh
      graft.

PMID- 19597917
TI  - Concurrent cocaine and alcohol use in individuals presenting to an addiction
      treatment program.
AB  - BACKGROUND: National population surveys and information from the National Drug
      Treatment Reporting System indicate cocaine use is increasing. There is a paucity
      of studies focusing on comorbid cocaine and alcohol use in Ireland. AIMS: The
      aims of the study are to examine comorbid cocaine and alcohol use patterns in
      those under 45 years, presenting to a national addiction treatment unit for
      alcohol and drug dependence. METHODS: A retrospective review of the substance
      misuse behavior of 465 individuals participating in an addiction rehabilitation
      programme for alcohol dependence. RESULTS: Cocaine use among this population rose
      significantly between 1995 (8%) and 2006 (37.9%). There was a significant
      association between lifetime reported cocaine use and both psychotic disorders
      and deliberate self harm. Overall, the use was highest among younger age group
      and this declined steadily with age. CONCLUSIONS: Cocaine use among the alcohol
      dependent population is an increasing problem in the Republic of Ireland, and
      poses a problem of higher toxicity associated with concurrent cocaine and alcohol
      use.

PMID- 19597919
TI  - Prospective study on long-term treatment with oxcarbazepine in pediatric
      epilepsy.
AB  - Following a previous preliminary report on a group of children suffering from
      partial epilepsies, we present the final considerations on the same group in
      order to evaluate the long-term efficacy, tolerability and safety of
      oxcarbazepine (OXC). We enrolled 36 patients (mean age 8.5), between January 2003
      and December 2004, with new diagnosis of partial epilepsy: 25 patients were
      affected by idiopathic partial epilepsy, eight by symptomatic epilepsy and three
      by cryptogenic epilepsy. Each patient was scheduled to attend the center four
      times after the initial examination: 3 months (T1), 12 months (T2), 24 (T3)
      months and 36 (T4) months after the beginning of OXC-monotherapy (T0). At the end
      of our study, 20 patients were seizure free (SF): nine stopped OXC because of SF
      for at least 2 years, 11 were still on therapy. One patient showed a reduction of
      seizure frequency >or=50%, three were non responders (but still on therapy), nine
      stopped OXC due to a non-responder condition during follow-up before T4 and one
      because of adverse effects. At the end of the study no EEG focal abnormalities
      became generalized because of treatment. Normalization of EEG was observed in ten
      patients. Our preliminary findings have been confirmed. OXC can be considered an
      effective and well tolerated first line drug for long-term monotherapy in
      children with epilepsy, both for idiopathic and symptomatic/cryptogenic forms.

PMID- 19597920
TI  - When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism
      spectrum disorders in primary school-aged children?
AB  - The aims of this study were, firstly, to study the association between parents'
      and teachers' ratings for the Finnish version of the Autism Spectrum Screening
      Questionnaire (ASSQ), secondly, to find out whether the original cut-off scores
      of the ASSQ identify primary school-aged children with Asperger syndrome (AS) or
      autism by using the Finnish ASSQ, and thirdly, to evaluate the validity of the
      ASSQ. Parents and/or teachers of higher-functioning (full-scale intelligence
      quotient > or = 50) 8-year-old total population school children (n = 4,408) and 7
      12-year-old outpatients with AS/autism (n = 47) completed the Finnish version of
      the ASSQ. Agreement between informants was slight. In the whole total population,
      low positive correlation was found between parents' and teachers' ratings, while
      in the sample of high-scoring children the correlation turned out to be negative.
      A cut-off of 30 for parents' and teacher's summed score and 22 for teachers'
      single score is recommended. A valid cut-off for parents' single score could not
      been estimated. The clinicians are reminded that the ASSQ is a screening
      instrument, not a diagnosing instrument. The importance of using both parents'
      and teachers' ratings for screening in clinical settings is underlined.

PMID- 19597921
TI  - Colchicine versus placebo in Behcet's disease: randomized, double-blind,
      controlled crossover trial.
AB  - The effect of colchicine was evaluated in a large cohort of Behcet's disease (BD)
      patients and compared to placebo. In a randomized, double-blind, controlled
      crossover trial, 169 patients without major organ involvement were selected
      consecutively. They fulfilled the International Criteria for Behcet's Disease.
      Patients were randomly assigned to colchicine or placebo. At 4 months, they were
      swapped over (colchicine to placebo, placebo to colchicine) for another 4 months.
      The primary outcome was the overall disease activity index, the IBDDAM. The
      secondary outcome was the responses of the individual symptoms. A Student's
      paired t test was used to evaluate results within each group, and an ANOVA to
      check for differences between colchicine and placebo. Analysis was performed
      using the "intention to treat" method. For placebo, IBDDAM worsened from 3.17 to
      3.63 (t = 1.750, P = 0.08). For colchicine, IBDDAM improved from 3.35 to 2.75 (t
      = 4.143, P < 0.0001). Oral aphthosis, genital aphthosis, pseudofolliculitis, and
      erythema nodosum improved significantly with colchicine but not with placebo.
      According to the ANOVA, the difference in IBDDAM between colchicine and placebo
      was highly significant (F = 14.674, P = 0.00016). The difference between the
      results for males and females was not significant (F = 0.181, P = 0.67). In
      conclusion, colchicine, but not placebo, significantly improved the overall
      disease activity index. The difference between the results for colchicine and
      placebo was also statistically significant.

PMID- 19597922
TI  - Tailor-made virtual lung: prevailing clinical application.

PMID- 19597923
TI  - Surgical strategy for pulmonary atresia with intact ventricular septum: initial
      management and definitive surgery.
AB  - Pulmonary atresia with intact ventricular septum is difficult to manage, and the
      surgical procedures are associated with high mortality and morbidity. The lesion
      is morphologically heterogeneous, with varying degrees of right ventricular and
      tricuspid valve hypoplasia. Aberrations of the coronary circulation are common. A
      single approach is impractical because the wide spectrum of right heart
      morphology makes a uniform surgical approach impossible. Anatomical criteria,
      such as the degree of tricuspid valve or right ventricular hypoplasia or whether
      a right ventricular infundibulum is present, have been used to assign the infants
      to single-ventricular or biventricular repair tracks. If the patient is
      considered a candidate for biventricular repair, right ventricular decompression,
      either alone or combined with a systemic-pulmonary artery shunt, is performed,
      whereas only a systemic-pulmonary artery shunt is performed in a candidate for
      single-ventricular repair. Several authors reported that the Z-value of the
      tricuspid valve diameter could be a guide to the initial procedure; however, poor
      interobserver reproducibility and wide normal ranges are serious limitations.
      Definitive operations, including biventricular repair, one-and-a-half ventricular
      repair, or Fontan-type operation, are performed to eliminate cyanosis. The most
      important problem when planning a strategy for a definitive repair is the fact
      that right ventricular growth and its contribution to pulmonary flow is difficult
      to predict before the operation. The management protocol should be determined by
      the precisely estimated morphology of the right ventricle and tricuspid valve,
      and the adequacy of the protocol should be analyzed based on surgical outcomes.

PMID- 19597925
TI  - Prediction of postoperative hepatic dysfunction after cardiac surgery in patients
      with chronic congestive heart failure.
AB  - OBJECTIVE: Chronic congestive liver dysfunction in advanced valvular disease
      remains an important co-morbidity in open heart surgery. The objective of this
      study was to explore the prognostic value in patients with severe valvular
      disease associated with congestive liver dysfunction. METHODS: From 1997 to 2004,
      a total of 63 patients who had valvular disease with moderate or severe tricuspid
      regurgitation were studied. In addition to the indocyanine green retention rate
      at 15 min (ICG15) and the Child-Pugh score, we measured serum total bilirubin (T
      bil), asparate aminotransferase (AST), alanine aminotransferase (ALT),
      cholinesterase (ChE), albumin (Alb) concentration, and prothrombin time. We
      compared these preoperative factors with postoperative liver dysfunction and
      mortality and attempted to develop a new liver function score. RESULTS: There
      were eight in-hospital deaths (13%). Seventeen patients had postoperative liver
      dysfunction. The univariate analysis indicated there were significant differences
      in preoperative T-bil, Alb, ChE, ICG15, and Child-Pugh score between the patients
      with and without liver dysfunction. Multivariate logistic regression analysis
      also identified preoperative T-bil as a significant indicator of postoperative
      liver dysfunction and preoperative ChE as a predictor of mortality. Based on
      these findings, we introduced a liver function score to predict postoperative
      dysfunction and death. CONCLUSION: In addition to preoperative ChE, T-bil and Alb
      appeared to be valuable for producing obtainable prognostic information regarding
      postoperative liver dysfunction in patients with severe valvular disease. A new
      liver score, including T-bil, ChE, and Alb, is proposed for predicting
      postoperative hepatic dysfunction and outcome.

PMID- 19597924
TI  - cDNA microarray analysis of esophageal cancer: discoveries and prospects.
AB  - Recent progress in molecular biology has revealed many genetic and epigenetic
      alterations that are involved in the development and progression of esophageal
      cancer. Microarray analysis has also revealed several genetic networks that are
      involved in esophageal cancer. However, clinical application of microarray
      techniques and use of microarray data have not yet occurred. In this review, we
      focus on the recent developments and problems with microarray analysis of
      esophageal cancer.

PMID- 19597927
TI  - Imaging aid for thoracic surgery: multidetector-row computed tomography
      evaluation of the tracheobronchial structure and bronchial tube selection for one
      lung anesthesia.
AB  - OBJECTIVE: The tracheobronchial structures were evaluated by multidetector-row
      computed tomography (MDCT), which provided imaging information for one-lung
      anesthesia during thoracic surgery. METHODS: The subjects consisted of 100
      patients. Three-dimensional (3D) images of the tracheobronchial structures and
      the bronchial tubes were created. RESULTS: Individual differences were found in
      the tracheobronchial structures in 100 patients. The length and the diameter of
      the right main bronchus were measured with 3D images and were not related to the
      patient's physical appearance, such as body height. Problematic intubation cases
      included a short right main bronchus <10 mm, an anomaly of the right bronchus,
      and tracheal stenosis. CONCLUSION: The 3D images demonstrated problematic areas
      of the tracheobronchial structure and helped the anesthesiologists select the
      most appropriate bronchial tube suitable for the tracheobronchial structure
      variations. Therefore, this technique is considered to contribute to safer
      performance of one-lung anesthesia.

PMID- 19597928
TI  - Surgical approach to left subclavian artery aneurysm in Marfan syndrome.
AB  - We present a case of left subclavian artery aneurysm in a 48-year-old man with
      Marfan syndrome. Aneurysmectomy and interposition with an artificial graft were
      successfully performed through an infraclavicular incision by dividing the
      clavicle at its midshaft. The clavicle bone was reconstructed with a steel plate,
      and the postoperative course was uneventful. Because the arterial wall is fragile
      in cases of connective tissue disorders such as Marfan syndrome, our surgical
      approach was considered to be helpful for gentle maneuvering in an adequate
      operative field.

PMID- 19597926
TI  - Cisplatin-based chemotherapy followed by surgery for malignant nonseminomatous
      germ cell tumor of mediastinum: one institution's experience.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
      cisplatin-based chemotherapy followed by surgery for patients with a malignant
      nonseminomatous germ cell tumor (NSGCT) of the mediastinum. METHODS: Ten patients
      with malignant NSGCTs received cisplatin-based induction chemotherapy and then
      underwent surgery. The clinicopathological characteristics of these 10 patients
      were examined retrospectively. RESULTS: A partial response to induction
      chemotherapy was noted in eight patients and no response in two. The induction
      chemotherapy was tolerated well by all the patients. Each patient underwent
      complete surgical resection of the residual tumor following chemotherapy. A yolk
      sac tumor was detected in one patient and malignant teratoma along with a yolk
      sac tumor in one patient postoperatively. The overall survival of the 10 patients
      was 67% at 60 months of follow-up. The survival rate at 60 months was poorer for
      the patients whose resected specimens exhibited the presence of viable cells than
      for those whose specimens were free of viable cells. CONCLUSION: Postchemotherapy
      surgical resection of the residual tumor plays an integral role in the management
      of patients with NSGCT. The presence of viable tumor cells in the resected
      specimens is associated with poor survival.

PMID- 19597929
TI  - Aortopulmonary fistula caused by penetrating atherosclerotic ulcer and intramural
      hematoma.
AB  - A 75-year-old woman presented with chronic cough and hemoptysis. Chest computed
      tomography (CT) and aortography revealed a small, contrast-filled outpouching in
      the wall of the descending aorta, which was thought to be the source of bleeding.
      At thoracotomy, there were firm adhesions between the descending aorta and the
      left S6. The aorta was clamped and the adhesions were removed revealing a defect
      in the aortic wall with thrombus. The defect was sutured. A penetrating
      atherosclerotic ulcer and intramural hematoma were diagnosed based on the
      radiological and operative findings.

PMID- 19597930
TI  - Solitary fibrous tumors of the pleura presenting satellite tumors.
AB  - A 29-year-old man presented with a mass in the left lower lung field on a chest
      radiograph obtained during a medical checkup. Computed tomography revealed a
      tumor adjacent to the diaphragm. A sessile tumor measuring 10.5 x 8.5 x 4.5 cm
      arising from the parietal pleura was resected. The tumor was accompanied by
      several little tumors on the nearby diaphragm. Pathologically, the major tumor
      consisted of typical spindle-shaped cells with myxoid degeneration. There was no
      increased cellularity, cellular pleomorphism, or a high mitotic count. In
      immunohistochemical studies, the spindle cells showed positive staining for CD34
      and were negative for bcl-2. The smaller tumors also consisted of myxoid
      degeneration. We diagnosed benign solitary fibrous tumor of the pleura with
      satellite tumors. We must be aware of the possibility of satellite tumors when we
      treat patients with a benign solitary fibrous tumor.

PMID- 19597931
TI  - Surgery for multiple and diffuse pulmonary arteriovenous fistulas during
      childhood.
AB  - We report an uncommon clinical case of multiple, diffuse pulmonary arteriovenous
      fistulas that occurred during childhood. A 15-year-old Japanese girl with
      multiple pulmonary arteriovenous fistulas presented with moderate hypoxemia and
      was treated by left lower lobectomy for complete resection of the arteriovenous
      fistulas. Clinical and radiographic features are presented.

PMID- 19597932
TI  - Life-threatening giant mediastinal cystic teratoma in a 4-month-old male baby.
AB  - Cystic teratomas of the mediastinum are rare and present with severe respiratory
      distress during childhood. Aspiration of the cyst is indicated to reduce the cyst
      volume, alleviate the patient's symptoms, and secure an operative field. This
      report describes a 4-month-old male baby with a large anterior mediastinal
      teratoma presenting with severe respiratory distress. The cystic teratoma was
      large enough to cause pectus carinatum. Respiratory distress secondary to airway
      obstruction was markedly reduced by percutaneous aspiration of the cyst. Surgical
      excision is indicated for a malignant or benign well-demarcated mass in any part
      of the mediastinum. In our patient, total surgical excision was performed.
      Preoperatively, percutaneous aspiration was performed twice, with the symptoms
      being reduced after each aspiration. Surgical excision is the best means of
      diagnosing and treating a benign teratoma. Percutaneous cyst aspiration not only
      improved ventilation but also facilitated easy excision of the cyst during
      surgical management.

PMID- 19597934
TI  - Quantitative estimation of plum pox virus targets acquired and transmitted by a
      single Myzus persicae.
AB  - The viral charge acquired and inoculated by single aphids in a non-circulative
      transmission is estimated using plum pox virus (PPV). A combination of electrical
      penetration graph and TaqMan real-time RT-PCR techniques was used to establish
      the average number of PPV RNA targets inoculated by an aphid in a single probe
      (26,750), approximately half of the acquired ones. This number of PPV targets is
      responsible for a systemic infection of 20% on the inoculated receptor plants. No
      significant differences were found between the number of PPV RNA targets acquired
      after one and after five intracellular punctures (pd), but the frequency of
      infected receptor plants was higher after 5 pd. The percentage of PPV-positive
      leaf discs after just 1 pd of inoculation probe (28%/4,603 targets) was lower
      than after 5 pd (45.8%/135 x 10(6) targets). The methodology employed could be
      easily extended to other virus-vector-host combinations to improve the accuracy
      of models used in virus epidemiology.

PMID- 19597933
TI  - Acute intrastriatal administration of quinolinic acid affects the expression of
      the coat protein AP-2 and its interaction with membranes.
AB  - Clathrin-coated vesicle endocytosis is thought to be crucial for the maintenance
      of synaptic transmission and for the cell plasticity at the nervous system. In
      this study, we demonstrated that acute intrastriatal administration of quinolinic
      acid (QUIN), an agonist of the N-methyl-D: -aspartate receptor, induces a
      decrease of the coat protein AP-2 expression and affects their interaction with
      membranes. By western blot analysis we observed that at 24 h after QUIN
      intrastriatal injection, alpha1 subunit of AP-2 and alpha2, at lesser extent,
      were reduced in the striatal membranes. The decrease of both subunits expression
      was extended to 48 h after treatment, although the soluble proteins were mostly
      affected. Other areas of the brain were not affected by the treatment, except the
      cerebellum, where a significant increase of soluble AP-2 (both subunits) was
      observed at 48 h after injection. Another coat protein, as the phosphoprotein AP
      180, was not affected by the injection of QUIN. We also confirmed that QUIN
      injection causes increasing loss of striatal neurons after the administration of
      the toxin. We concluded that QUIN may affect the endocytotic machinery of the
      striatum, by inducing changes in the AP-2 behaviour. Consequently, the
      internalization of NMDAR and/or AMPAR may be affected, by QUIN, contributing to
      the excitotoxic effect of the drug.

PMID- 19597935
TI  - Cystatin like thiol proteinase inhibitor from pancreas of Capra hircus:
      purification and detailed biochemical characterization.
AB  - A thiol proteinase inhibitor from Capra hircus (goat) pancreas (PTPI) isolated by
      ammonium sulphate precipitation (20-80%) and gel filtration chromatography on
      Sephacryl S-100HR, with 20.4% yield and 500-fold purification, gave molecular
      mass of 44 kDa determined by its electrophoretic and gel filtration behavior,
      respectively. The stokes radius, diffusion and sedimentation coefficients of PTPI
      were 27.3 A, 7.87 x 10(-7) cm(2) s(-1) and 3.83 s, respectively. It was stable in
      pH range 3-10 and up to 70 degrees C (critical temperature, E (a) = 21 kJ mol(
      1)). Kinetic analysis revealed reversible and competitive mode of inhibition with
      PTPI showing the highest inhibitory efficiency against papain (K ( i ) = 5.88
      nM). The partial amino acid sequence analysis showed that it shared good homology
      with bovine parotid and skin cystatin C. PTPI possessed 17.18% alpha helical
      content assessed by CD spectroscopy. The hydropathy plot of first 24 residues
      suggested that most amino acids of this stretch might be in the hydrophobic core
      of the protein.

PMID- 19597936
TI  - Sushi-roll wrap of Seprafilm for ileostomy limbs facilitates ileostomy closure.
AB  - BACKGROUND: Sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm)
      reduced postoperative intraabdominal adhesion. In this study, we examined whether
      Seprafilm reduces operative difficulties in ileostomy closure. PATIENTS AND
      METHODS: During the creation of the ileostomy, Seprafilm was cut in half and used
      to wrap both the ileum and mesentery. Patients who underwent ileostomy closure
      before February 2008 (without Seprafilm, Group T, n = 18) and after March (with
      Seprafilm, Group S, n = 18) were enrolled in this study. All operations were
      performed by surgical residents. Operative time and perioperative complications
      were analyzed. RESULTS: The mean operative time of Group S (106.88 min) was
      significantly less than that of Group T (120.6 min). The amount of intraoperative
      bleeding in Groups S and T was not significantly different and there were no
      major complications. CONCLUSION: Seprafilm applied to the two limbs of the
      ileostomy and mesentery facilitate ileostomy closure done by non-expert surgeons.

PMID- 19597937
TI  - Perirectal abscess following procedure for prolapsed haemorrhoids successfully
      managed with a combination of VAC sponge and Redivac systems.
AB  - Active drains, which work from negative pressure effect, are commonly used to
      drain closed airtight wounds. Higher negative pressure is used in vacuum assisted
      wound closure (VAC) (usually -125 mmHg) dressings and in Redivac system (usually 
      300 mmHg). As far as we know, combinations of Redivac and VAC have not been used.
      The authors describe a novel combination using the sponge of the VAC dressing and
      sealed Redivac system to drain an open rectal wound, consequence of a perforation
      after stapled haemorrhoidopexy.

PMID- 19597938
TI  - A new flap technique to treat pilonidal sinus.
AB  - BACKGROUND: Failures of flap rotation, flap necrosis, recurrence of the disease,
      maceration at the incisional line and insufficient or late healing of flap
      corners which can be associated with ischemia appear to be the main problems
      associated with the closing techniques during the surgical treatment of this
      disease. We describe a simple, effective and incision protective repair method
      for excision of the pilonidal cyst. METHODS: Data from 17 (12 males and 5
      females) consecutive patients who had elective surgery for chronic pilonidal
      sinus disease with wide excision of all the sinuses and a new flap technique
      closure with adipo-fascio-cutaneous flaps which was used in our series for the
      treatment of pilonidal sinus disease were retrospectively analyzed. RESULTS:
      Satisfactory results were achieved with this flap rotation technique in 17
      patients. There were no flap rotation failures, flap necrosis, disease
      recurrence, incisional line maceration, or delayed wound healing. CONCLUSION: As
      a result, presented technique provides avoidance of flap necrosis, maceration on
      the incision and insufficient or late healing of the flap. We describe a
      technique which has a minimal amount of scar across the midline natal cleft and
      fewer flap corners resulting in a lower chance of margin necrosis.

PMID- 19597939
TI  - Headache, cardiac arrest, and intracranial hemorrhage.
AB  - Headache is one of the most common manifestations of non-traumatic intracranial
      hemorrhage, which is an uncommon, but not rare, cause of cardiac arrest in
      adults. History of a sudden headache preceding collapse may be a helpful clue to
      estimate the cause of out-of-hospital cardiac arrest (OHCA). Medical records of
      witnessed OHCA patients were reviewed to identify those who complained of a
      sudden headache preceding collapse, and the incidence of intracranial hemorrhage
      among them as well as their clinical characteristics was investigated
      retrospectively. During the 12-month period, 124 patients who sustained a
      witnessed OHCA were treated. Among them, 74 (60%) collapsed without any pain
      complaint, and only 6 (5%) complained of a sudden headache preceding collapse.
      All of the six patients were resuscitated: four had a severe subarachnoid
      hemorrhage (SAH), while the other two had a massive cerebellar hemorrhage. By
      contrast, 39 of the 74 patients who collapsed without any pain were resuscitated.
      Among them, another six patients were found to harbor an SAH. Thus, a total of 12
      among the 124 witnessed OHCA (10%) sustained a fatal intracranial hemorrhage.
      While OHCA patients who collapse complaining of a sudden headache are uncommonly
      seen in the emergency room, they have a high likelihood of harboring a severe
      intracranial hemorrhage. It should also be reminded that approximately half of
      patients whose cardiac arrest is due to an intracranial hemorrhage may collapse
      without complaining of a headache. The prognosis of those with cerebral origin of
      OHCA is invariably poor, although they may relatively easily be resuscitated
      temporarily. Focus needs to be directed to avoid sudden death from a potentially
      treatable cerebral lesion, and public education to promote the awareness for the
      symptoms of potentially lethal hemorrhagic stroke is warranted.

PMID- 19597940
TI  - Chronic inflammation as a manifestation of defects in immunoregulatory networks:
      implications for novel therapies based on microbial products.
AB  - Based on a unifying theory presented here, it is predicted that the immune
      defects resulting in chronic inflammation rather than effective immune responses
      could be rectified by the therapeutic use of agents prepared from micro
      organisms. With appropriate molecular patterns, these should be able to induce
      protective immunoregulatory networks or to reprogramme defective ones. In
      contrast to acute inflammation, chronic inflammation appears to have no
      beneficial role, but is a state of sustained immune reactivity in the presence or
      progression of a disease process. This results in an escalating cycle of tissue
      damage followed by unproductive tissue repair, breaks in self-tolerance,
      malignant transformation or deleterious changes in tissue morphology and
      function. Such inappropriate immune reactivity is an underlying characteristic,
      either in initiation or maintenance, of a diverse range of disease states
      including chronic infection, autoimmunity, allergy, cancer, vascular disease and
      metabolic alterations. Evidence is presented that the inappropriate immune
      reactivity is due, at least to some extent, to failures in the establishment of
      immunoregulatory networks as a result of hygiene-related factors. Such networks
      are the result of activation of antigen-presenting cells, principally dendritic
      cells, by molecular patterns of micro-organisms encountered sequentially during
      life and establishing the 'biography' of the immune system.

PMID- 19597941
TI  - Molecular dynamics simulation of S100B protein to explore ligand blockage of the
      interaction with p53 protein.
AB  - As a tumor suppressor, p53 plays an important role in cancer suppression. The
      biological function of p53 as a tumor suppressor is disabled when it binds to
      S100B. Developing the ligands to block the S100B-p53 interaction has been
      proposed as one of the most important approaches to the development of anti
      cancer agents. We screened a small compound library against the binding interface
      of S100B and p53 to identify potential compounds to interfere with the
      interaction. The ligand-binding effect on the S100B-p53 interaction was explored
      by molecular dynamics at the atomic level. The results show that the ligand bound
      between S100B and p53 propels the two proteins apart by about 2 A compared to the
      unligated S100B-p53 complex. The binding affinity of S100B and p53 decreases by
      ~8.5-14.6 kcal/mol after a ligand binds to the interface from the original
      unligated state of the S100B-p53 complex. Ligand-binding interferes with the
      interaction of S100B and p53. Such interference could impact the association of
      S100B and p53, which would free more p53 protein from the pairing with S100B and
      restore the biological function of p53 as a tumor suppressor. The analysis of the
      binding mode and ligand structural features would facilitate our effort to
      identify and design ligands to block S100B-p53 interaction effectively. The
      results from the work suggest that developing ligands targeting the interface of
      S100B and p53 could be a promising approach to recover the normal function of p53
      as a tumor suppressor.

PMID- 19597942
TI  - Automated NMR structure determination of stereo-array isotope labeled ubiquitin
      from minimal sets of spectra using the SAIL-FLYA system.
AB  - Stereo-array isotope labeling (SAIL) has been combined with the fully automated
      NMR structure determination algorithm FLYA to determine the three-dimensional
      structure of the protein ubiquitin from different sets of input NMR spectra. SAIL
      provides a complete stereo- and regio-specific pattern of stable isotopes that
      results in sharper resonance lines and reduced signal overlap, without
      information loss. Here we show that as a result of the superior quality of the
      SAIL NMR spectra, reliable, fully automated analyses of the NMR spectra and
      structure calculations are possible using fewer input spectra than with
      conventional uniformly 13C/15N-labeled proteins. FLYA calculations with SAIL
      ubiquitin, using a single three-dimensional "through-bond" spectrum (and 2D HSQC
      spectra) in addition to the 13C-edited and 15N-edited NOESY spectra for
      conformational restraints, yielded structures with an accuracy of 0.83-1.15 A for
      the backbone RMSD to the conventionally determined solution structure of SAIL
      ubiquitin. NMR structures can thus be determined almost exclusively from the
      NOESY spectra that yield the conformational restraints, without the need to
      record many spectra only for determining intermediate, auxiliary data of the
      chemical shift assignments. The FLYA calculations for this report resulted in 252
      ubiquitin structure bundles, obtained with different input data but identical
      structure calculation and refinement methods. These structures cover the entire
      range from highly accurate structures to seriously, but not trivially, wrong
      structures, and thus constitute a valuable database for the substantiation of
      structure validation methods.

PMID- 19597943
TI  - A refinement protocol to determine structure, topology, and depth of insertion of
      membrane proteins using hybrid solution and solid-state NMR restraints.
AB  - To fully describe the fold space and ultimately the biological function of
      membrane proteins, it is necessary to determine the specific interactions of the
      protein with the membrane. This property of membrane proteins that we refer to as
      structural topology cannot be resolved using X-ray crystallography or solution
      NMR alone. In this article, we incorporate into XPLOR-NIH a hybrid objective
      function for membrane protein structure determination that utilizes solution and
      solid-state NMR restraints, simultaneously defining structure, topology, and
      depth of insertion. Distance and angular restraints obtained from solution NMR of
      membrane proteins solubilized in detergent micelles are combined with backbone
      orientational restraints (chemical shift anisotropy and dipolar couplings)
      derived from solid-state NMR in aligned lipid bilayers. In addition, a
      supplementary knowledge-based potential, E (z) (insertion depth potential), is
      used to ensure the correct positioning of secondary structural elements with
      respect to a virtual membrane. The hybrid objective function is minimized using a
      simulated annealing protocol implemented into XPLOR-NIH software for general use.

PMID- 19597946
TI  - Isolation and characterization of rice straw degrading Streptomyces griseorubens
      C-5.
AB  - To reutilize rice straw generated during the agricultural production process, the
      actinomycete strain C-5 was isolated from soil that was under the stook for
      several years in the Heilongjiang province of China by using multiple selective
      culture media. Strain C-5 was identified as Streptomyces griseorubens by China
      General Microbiological Culture Collection Center (CGMCC) through morphological
      and physiological characterization combined with the result of 16S rRNA gene
      sequence and data analysis. This strain has simultaneous cellulase, laccase,
      peroxidase, xylanase and pectinase activity. The various chemical composition of
      rice straw were determined during fermentation process. Simultaneously the
      biodegradation process of rice straw stem was observed by scanning electron
      microscope (SEM). It is predicted that strain C-5 could decompose rice straw
      effectively and had promising prospects of being applied in improving the
      resource utilization of rice straw.

PMID- 19597944
TI  - Arabidopsis thaliana encodes a bacterial-type heterodimeric isopropylmalate
      isomerase involved in both Leu biosynthesis and the Met chain elongation pathway
      of glucosinolate formation.
AB  - The last steps of the Leu biosynthetic pathway and the Met chain elongation cycle
      for glucosinolate formation share identical reaction types suggesting a close
      evolutionary relationship of these pathways. Both pathways involve the
      condensation of acetyl-CoA and a 2-oxo acid, isomerization of the resulting 2
      malate derivative to form a 3-malate derivative, the oxidation-decarboxylation of
      the 3-malate derivative to give an elongated 2-oxo acid, and transamination to
      generate the corresponding amino acid. We have now analyzed the genes encoding
      the isomerization reaction, the second step of this sequence, in Arabidopsis
      thaliana. One gene encodes the large subunit and three encode small subunits of
      this enzyme, referred to as isopropylmalate isomerase (IPMI) with respect to the
      Leu pathway. Metabolic profiling of large subunit mutants revealed accumulation
      of intermediates of both Leu biosynthesis and Met chain elongation, and an
      altered composition of aliphatic glucosinolates demonstrating the function of
      this gene in both pathways. In contrast, the small subunits appear to be
      specialized to either Leu biosynthesis or Met chain elongation. Green fluorescent
      protein tagging experiments confirms the import of one of the IPMI small subunits
      into the chloroplast, the localization of the Met chain elongation pathway in
      these organelles. These results suggest the presence of different heterodimeric
      IPMIs in Arabidopsis chloroplasts with distinct substrate specificities for Leu
      or glucosinolate metabolism determined by the nature of the different small
      subunit.

PMID- 19597945
TI  - Sexual selection and the rodent baculum: an intraspecific study in the house
      mouse (Mus musculus domesticus).
AB  - The rapid divergence of genitalia is a pervasive trend in animal evolution,
      thought to be due to the action of sexual selection. To test predictions from the
      sexual selection hypothesis, we here report data on the allometry, variation,
      plasticity and condition dependence of baculum morphology in the house mouse (Mus
      musculus domesticus). We find that that baculum size: (a) exhibits no consistent
      pattern of allometric scaling (baculum size being in most cases unrelated to body
      size), (b) exhibits low to moderate levels of phenotypic variation, (c) does not
      exhibit phenotypic plasticity in response to differences in perceived levels of
      sexual competition and (d) exhibits limited evidence of condition dependence.
      These patterns provide only limited evidence in support of the sexual selection
      hypothesis, and no consistent support for any particular sexual selection
      mechanism; however, more direct measures of how genital morphology influences
      male fertilization success are required.

PMID- 19597947
TI  - Can microbially-generated hydrogen sulfide account for the rates of U(VI)
      reduction by a sulfate-reducing bacterium?
AB  - In situ remediation of uranium contaminated soil and groundwater is attractive
      because a diverse range of microbial and abiotic processes reduce soluble and
      mobile U(VI) to sparingly soluble and immobile U(IV). Often these processes are
      linked. Sulfate-reducing bacteria (SRB), for example, enzymatically reduce U(VI)
      to U(IV), but they also produce hydrogen sulfide that can itself reduce U(VI).
      This study evaluated the relative importance of these processes for Desulfovibrio
      aerotolerans, a SRB isolated from a U(VI)-contaminated site. For the conditions
      evaluated, the observed rate of SRB-mediated U(VI) reduction can be explained by
      the abiotic reaction of U(VI) with the microbially-generated H(2)S. The presence
      of trace ferrous iron appeared to enhance the extent of hydrogen sulfide-mediated
      U(VI) reduction at 5 mM bicarbonate, but had no clear effect at 15 mM. During the
      hydrogen sulfide-mediated reduction of U(VI), a floc formed containing uranium
      and sulfur. U(VI) sequestered in the floc was not available for further
      reduction.

PMID- 19597948
TI  - The literature on forensic acarology. Preface.

PMID- 19597949
TI  - Multi-channel electrical bioimpedance: a non-invasive method to simultaneously
      measure cardiac output and individual arterial limb flow in patients with
      cardiovascular disease.
AB  - BACKGROUND: Cardiac output is the fundamental determinant of peripheral blood
      flow however; optimal regional tissue perfusion is ultimately dependant on the
      integrity of the arterial conduits that transport flow. A complete understanding
      of tissue perfusion requires knowledge of both cardiac and peripheral blood flow.
      Existing noninvasive devices do not simultaneously assess the cardiac and
      peripheral circulations. Multi-channel electrical bioimpedance (MEB) measures
      cardiac output and peripheral flow simultaneously. OBJECTIVES: Assessment of the
      accuracy of MEB to measure cardiac output in patients with clinical heart failure
      (group 1) and to measure regional arterial limb flow in patients with exertional
      leg pain clinically thought to have peripheral arterial disease (group 2).
      METHODS: Cardiac output was measured by MEB in 44 patients with moderate to
      severe clinical heart failure (group 1) and was compared to a cardiac output
      measured by 2D-Echo Doppler. Peripheral blood flow (regional ankle and arm flow)
      was measured by MEB in another group of 25 patients with exertional leg pain
      clinically thought to be claudication (group 2). The MEB ankle/arm flow ratio
      (AAI index) was then compared to a conventional ankle/brachial pressure ratio
      (ABI index). RESULTS: There was excellent correlation between the mean cardiac
      index by MEB (2.01 l/min/m(2)) and by 2D-Echo Doppler (2.06 l/min/m(2)) and bias
      and precision was 0.05 (2.4%) and +/-0.48 l/min/m(2) (+/-23%), respectively. The
      correlation was maintained for each measurement over a wide range of cardiac
      indices. There was good correlation between AAI and ABI measurements (P < 0.05).
      CONCLUSIONS: MEB accurately measures cardiac output in patients with moderate to
      severe clinical heart failure and accurately measures regional arterial limb flow
      in patients with peripheral arterial disease.

PMID- 19597951
TI  - Evaluation of geochemical associations as a screening tool for identifying
      anthropogenic trace metal contamination.
AB  - Geochemical association plots are used as a screening tool for environmental site
      assessments and use empirical log-log relationships between total trace metal
      concentrations and concentrations of a major (i.e., reference) soil metal
      constituent, such as iron (Fe), to discern sites with naturally elevated trace
      metal levels from sites with anthropogenic contamination. Log-log relationships
      have been consistently observed between trace metal and reference metal
      concentrations and are often considered constant. Consequently, we used a
      regional geochemistry data set to evaluate background trace metal/Fe log-log
      associations across soils with highly diverse composition. Our results indicate
      that, although geochemical associations may be proportional, they significantly
      differ across predominant United States Department of Agriculture (USDA) soil
      orders. This suggests that highly complex interactions between soil-forming
      factors and variable secondary clay mineral composition affect the ratio of trace
      metals to Fe concentrations in soils. Also, intra-order variability in trace
      metal/Fe ratios generally ranged multiple orders of magnitude which suggest that
      the order level of the USDA soil taxonomic system is insufficient to reasonably
      classify background trace metal concentrations. Consequently, geochemical
      association plots are a useful screening tool for environmental site assessments,
      but ubiquitous application of generic background metal data sets could result in
      erroneous conclusions. Because significantly different ratios were observed
      across predominant USDA soil orders, an agglomerative clustering technique was
      used to elucidate hierarchical patterns of association. We present these results
      as a mechanism to aid environmental assessors in screening candidate background
      metal data sets for their applicability to site-specific soil composition;
      although site-specific background metal data should be utilized if ample pristine
      reference sites with similar (i.e., sub-order) soil composition can be identified
      and sampled.

PMID- 19597950
TI  - Jasmine tea consumption and upper gastrointestinal cancer in China.
AB  - INTRODUCTION: Epidemiological data on green/jasmine tea and esophageal as well as
      gastric cancer are limited and inconclusive. METHODS: In order to study the
      effect of jasmine tea in upper gastrointestinal (UGI) cancers, we evaluated 600
      esophageal squamous cell carcinoma (ESCC), 598 gastric cardia cancer (GCA), and
      316 gastric non-cardia cancer (GNCA) cases and 1,514 age-, gender-, and
      neighborhood-matched controls. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were estimated from logistic regression adjusted for matching factors and
      potential confounders. RESULTS: Among controls, 35% of males and 8% of females
      reported consumption of jasmine tea; other tea consumption was rare. Consumption
      of jasmine tea (ever vs. never) was not associated with risk of ESCC (OR = 1.15,
      95% CI 0.92-1.44), GCA (OR = 1.14, 95% CI 0.88-1.37), or GNCA (OR = 0.85, 95% CI
      0.64-1.15) in males and females combined. Among males, cumulative lifetime
      consumption showed a significant positive dose-response relation with ESCC risk,
      but not for GCA and GNCA. In exploratory analyses, occupation affected the
      relation between tea and ESCC such that consumption in males was associated with
      increased risk only in non-office workers. CONCLUSION: Overall, we found no
      evidence for a protective effect of tea in esophageal or gastric cancer. Further
      studies of the potential effects of thermal damage, tea quality, and water
      quality on UGI cancers are suggested.

PMID- 19597952
TI  - Antimicrobial resistance in Clostridium perfringens isolates from broilers in
      Belgium.
AB  - The antimicrobial susceptibility of Clostridium perfringens strains isolated from
      Belgian broilers between May and September 2007 was investigated. All 39 tested
      isolates were sensitive to enrofloxacin, erythromycin, tylosin, florfenicol and
      bacitracin. Twenty-six (66%) and 24 (61%) out of the 39 tested isolates showed
      acquired resistance to tetracycline and lincomycin, respectively. The C.
      perfringens isolates were also screened by PCR for the presence of the resistance
      genes tet(K), tet(L), tet(M), tetB(P), tet(O), tet(W), lnu(A) and lnu (B). In
      22/26 tetracycline resistant strains and 7/24 lincomycin resistant strains,
      resistance could be attributed to one or more of these genes. An extended
      frequency distribution range of MICs was seen for ampicillin. These data are
      consistent with data derived from studies carried out in 1980 and in 2004,
      indicating that no changes in antimicrobial resistance patterns have taken place
      during time in C. perfringens isolates from broilers in Belgium.

PMID- 19597954
TI  - Dexmedetomidine chemical restraint of two raptor species undergoing inhalation
      anaesthesia.

PMID- 19597953
TI  - Alteration of gene expression in muscle tissue and mammary gland from recombinant
      somatotropin treated animals: searching for biomarkers.

PMID- 19597955
TI  - Reconstruction of calf oocytes by germinal vesicle transfer in mature bovine
      oocytes: preliminary results.

PMID- 19597956
TI  - From eco-sustainability to risk assessment of aquaculture products.
AB  - The increasing demand for fishery products and the technical and commercial
      opportunities now available make the development of aquaculture an important
      subject for the policy of the fishery sector, in particular concerning aspects of
      its environmental and ecological sustainability. The latest studies show that it
      is possible to apply an ecological approach to the aquaculture sector and hence
      increase the interactions between fisheries and other activities such as
      fish/molluscs, fish/seaweed, rice-growing/fish. In this way we take part in the
      improvement of the environment thanks to the recycling of organic food, the
      reduction of pesticide use and the control of environmental euthrophication. In
      order to support and facilitate trade, but at the same time ensure the safety and
      quality of products, a harmonization of the policies for food safety protecting
      the products throughout the whole food chain is required (from the sea to the
      table). The above mentioned policy, based on scientific knowledge, relies on the
      analysis of risks from the competent Authorities and on the proper application of
      HACCP from the industries of the sector.

PMID- 19597957
TI  - LXII Annual Meeting of the Italian Society for Veterinary Sciences (SISVET), San
      Benedetto del Tronto (Ascoli Piceno) 2008. Preface.

PMID- 19597958
TI  - Clinical characteristics and outcomes of rural patients with ESRD in Guangxi,
      China: one dialysis center experience.
AB  - OBJECTIVES: End-stage renal disease (ESRD) is a serious public health problem in
      Guangxi, a province of south China. This prospective study evaluated the
      characteristics and outcome of rural patients with ESRD in a dialysis center of
      Guangxi, compared with urban patients in the same period. METHODS: A total of 238
      patients (96 rural and 142 urban) who enrolled in 2007 was included in this study
      and followed up for 1 year. Clinical data including patient basic information,
      clinical parameters, laboratory tests, data associated with dialysis and
      prognosis were evaluated and compared between rural and urban groups. RESULTS:
      Glomerulonephritis was found to be the most common cause of ESRD in all the
      cohorts studied, with similar rates of 47.9 and 46.5% in the rural and urban
      patients, respectively. Compared to urban patients, the rural patients had
      significantly lower prevalence of diabetic nephropathy (8.3 vs. 24.6%, P < 0.001)
      and higher prevalence of obstructive uropathy (20.8 vs. 3.5%, P < 0.001); the
      rural patients were overall younger, with poorer financial supports, but with
      higher rates of late referrals, poorer renal functions as indicated by related
      laboratory tests including lower levels of GFR, serum hemoglobin, bicarbonate and
      Kt/V, but higher prevalence of very low GFR, severe metabolic acidosis, severe
      anemia and hyperkalemia, higher rate of not initiating dialysis, radial artery
      puncture and mortality. The cardiovascular events were found to be the most
      common cause of death in both rural and urban groups. CONCLUSIONS:
      Glomerulonephritis was found to be the most common cause of ESRD in all the
      studied patients. The rural patients with ESRD in Guangxi had kidney disease in
      more advanced stage at the time of first visit to a nephrologist and higher rates
      of mortality after dialysis initiation, compared to urban patients.

PMID- 19597959
TI  - Caenorhabditis elegans lifespan extension caused by treatment with an orally
      active ROS-generator is dependent on DAF-16 and SIR-2.1.
AB  - In Caenorhabditis elegans pretreatment with juglone, a generator of reactive
      oxygen species (ROS) provides a subsequently increased ROS-resistance. We
      investigated whether juglone at low or high concentrations when provided via the
      oral route in a liquid axenic medium affects normal lifespan of C. elegans. High
      juglone concentrations led to premature death, low concentrations were tolerated
      well and caused a prolongation of lifespan. Lifespan extension under moderate
      oxidative stress was associated with increased expression of small heat-shock
      protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF
      16. Silencing or deletion of DAF-16 prevented the juglone-induced adaptations.
      RNA-interference for SIR-2.1 had the same effects as the deletion of DAF-16 but
      did not affect nuclear accumulation of DAF-16. Our studies demonstrate that DAF
      16- and SIR-2.1-dependent alterations in gene expression after a ROS challenge
      lead to a lifespan extension in C. elegans as long as the stressor concentration
      does not exceed the saturable protective capacity.

PMID- 19597961
TI  - Isolation and characterization of a novel EAR-motif-containing gene GmERF4 from
      soybean (Glycine max L.).
AB  - Transcriptional repressors are emerging as central regulators of development and
      stress responses in different organisms. The ERF-associated amphiphilic
      repression (EAR) motif was identified as essential for transcriptional
      repression. To gain a better understanding of this type of protein, we reported
      here a novel GmERF4 protein from soybean. Sequence alignment showed that GmERF4
      contains one AP2/ERF domain, two putative nuclear localization signal regions and
      one EAR motif. The GmERF4 protein was preferentially localized to the nucleus of
      onion epidermis cells and bound specifically to the GCC box and DRE/CRT element
      in vitro. Furthermore, the expression of GmERF4 was induced by ethylene, JA, SA,
      cold, salt, drought, and soybean mosaic virus, and repressed by ABA. Constitutive
      expression of GmERF4 in transgenic tobacco plants increased tolerance to salt and
      drought stresses compared with wild-type plants, but did not exhibit detectable
      resistance against bacterial infection.

PMID- 19597960
TI  - Mortality and cause of death in mucopolysaccharidosis type II-a historical review
      based on data from the Hunter Outcome Survey (HOS).
AB  - Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a progressive,
      multisystemic disease caused by a deficiency of iduronate-2-sulfatase. Patients
      with the severe form of the disease have cognitive impairment and typically die
      in the second decade of life. Patients with the less severe form do not
      experience significant cognitive involvement and may survive until the fifth or
      sixth decade of life. We studied the relationship of both severity of MPS II and
      the time period in which patients died with age at death in 129 patients for whom
      data were entered retrospectively into HOS (Hunter Outcome Survey), the only
      large-scale, multinational observational study of patients with MPS II. Median
      age at death was significantly lower in patients with cognitive involvement
      compared with those without cognitive involvement (11.7 versus 14.1 years; p =
      0.024). These data indicate that cognitive involvement is indicative of more
      severe disease and lower life expectancy in patients with MPS II. Median age at
      death was significantly lower in patients who died in or before 1985 compared
      with those who died after 1985 (11.3 versus 14.1 years; p alpha 0.001). The
      difference in age at death between patients dying in or before, relative to
      after, the selected cut-off date of 1985 may reflect improvements in patient
      identification, care and management over the past two decades. Data from patients
      who died after 1985 could serve as a control in analyses of the effects of enzyme
      replacement therapy with idursulfase on mortality in patients with MPS II.

PMID- 19597962
TI  - A microarray study of altered gene expression in colorectal cancer cells after
      treatment with immunomodulatory drugs: differences in action in vivo and in
      vitro.
AB  - Thalidomide and lenalidomide are FDA approved for the treatment of multiple
      myeloma, and along with pomalidomide are being investigated in a variety of other
      cancers. Although these agents display immunomodulatory, anti-angiogenic and anti
      apoptotic effects, little is known about the primary mode of therapeutic action
      in patients with cancer. This paper describes a microarray study of the in vitro
      and in vivo effects of these drugs, and contrasts the difference in gene profiles
      achieved in the two models. In the current study, Agilent whole mouse genome
      oligonucleotide microarrays (44 K) were used to examine alterations in gene
      expression of colorectal cancer cells after treatment. Venn analysis revealed a
      divergence of gene signature for pomalidomide and lenalidomide, which although
      similar in vitro, different in vivo. Several clusters of genes involved in
      various cellular processes such as immune response, cell signalling and cell
      adhesion were altered by treatment, and common to the three drugs. Notably, the
      expressions of linked genes within the Notch/Wnt signalling pathway, including
      kremen2 and dtx4, highlighted a possible novel mechanistic pathway for these
      drugs. This study also showed that gene signatures were not greatly divergent in
      the models, and recapitulated the complex nature of these drugs. Overall, these
      microarray studies highlighted the diversity of this class of drug, which have
      effects ranging from cell signalling to translation initiation.

PMID- 19597963
TI  - The bifunctional role of LiuE from Pseudomonas aeruginosa, displays additionally
      HIHG-CoA lyase enzymatic activity.
AB  - Pseudomonas aeruginosa is able to utilize leucine/isovalerate and acyclic
      terpenes as sole carbon sources. Key enzymes which play an important role in
      these catabolic pathways are 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) lyase
      (EC 4.1.3.4; HMG-CoA lyase) and the 3-hydroxy-3-isohexenylglutaryl-CoA lyase (EC
      4.1.2.26; HIHG-CoA lyase), respectively. HMG-CoA lyase is encoded by the liuE
      gene while the gene for HIHG-CoA lyase remains unidentified. A mutant in the liuE
      gene was unable to utilize both leucine/isovalerate and acyclic terpenes
      indicates an involvement of liuE in both catabolic pathways (Chavez-Aviles et al.
      2009, FEMS Microbiol Lett 296:117-123). The LiuE protein was purified as a His
      tagged recombinant protein and in addition to show HMG-CoA lyase activity (Chavez
      Aviles et al. 2009, FEMS Microbiol Lett 296:117-123), also displays HIHG-CoA
      lyase activity, indicating a bifunctional role in both the leucine/isovalerate
      and acyclic terpenes catabolic pathways.

PMID- 19597965
TI  - Temporal indiscriminateness: the case of cluster bombs.
AB  - This paper argues that the current stock of anti-personnel cluster bombs are
      temporally indiscriminate, and, therefore, unjust weapons. The paper introduces
      and explains the idea of temporal indiscriminateness. It argues that to honor non
      combatant immunity-in addition to not targeting civilians-one must adequately
      target combatants. Due to their high dud rate, cluster submunitions fail to
      target combatants with sufficient temporal accuracy, and, thereby, result in
      avoidable serious harm to non-combatants. The paper concludes that non-combatant
      immunity and the principle of discrimination require a moratorium on the use of
      current cluster munitions.

PMID- 19597966
TI  - Analysis of citations to biomedical articles affected by scientific misconduct.
AB  - We describe the ongoing citations to biomedical articles affected by scientific
      misconduct, and characterize the papers that cite these affected articles. The
      citations to 102 articles named in official findings of scientific misconduct
      during the period of 1993 and 2001 were identified through the Institute for
      Scientific Information Web of Science database. Using a stratified random
      sampling strategy, we performed a content analysis of 603 of the 5,393 citing
      papers to identify indications of awareness that the cited articles affected by
      scientific misconduct had validity issues, and to examine how the citing papers
      referred to the affected articles. Fewer than 5% of citing papers indicated any
      awareness that the cited article was retracted or named in a finding of
      misconduct. We also tested the hypothesis that affected articles would have fewer
      citations than a comparison sample; this was not supported. Most articles
      affected by misconduct were published in basic science journals, and we found
      little cause for concern that such articles may have affected clinical equipoise
      or clinical care.

PMID- 19597964
TI  - Psychometric validation of two patient-reported outcome measures to assess
      symptom severity and changes in symptoms in hereditary angioedema.
AB  - PURPOSE: Hereditary angioedema (HAE) is a rare disorder characterized by highly
      variable, acute attacks of swelling at various anatomical locations. Clinical
      measures do not adequately assess the diversity of symptoms characteristic of an
      attack. Two disease-specific, patient-reported outcome measures were developed to
      comprehensively capture symptom severity and change: the Treatment Outcome Score
      (TOS) and the Mean Symptom Complex Severity (MSCS) score. METHODS: This study
      comprised a secondary analysis of pooled data from a randomized controlled trial
      to evaluate the psychometric properties, including reliability and validity, and
      minimally important difference (MID) of the TOS and MSCS score. RESULTS: HAE
      patients (n = 73) had a mean age of 33 years, and 60% were female. Test-retest
      evaluation demonstrated moderate to substantial agreement (ICCs = 0.53 for TOS;
      0.62 for MSCS score). The TOS and change in MSCS score were moderately to highly
      correlated with a Global Improvement Measure at 4 h (TOS: r = 0.90; MSCS: r = 
      0.59). Anchor- and distribution-based analyses suggested that conservative
      estimates for MID are 30 points for TOS and -0.30 points for 4-h change in MSCS
      score. CONCLUSIONS: The psychometric tests performed here provide evidence of the
      reliability and validity of the TOS and MSCS for evaluating symptom severity and
      change in HAE patients. The TOS and MSCS score provide an example of measurement
      methodology that may be used to precisely capture symptom severity and change in
      a disease characterized by acute attacks.

PMID- 19597967
TI  - Mobile-centric ambient intelligence in health- and homecare-anticipating ethical
      and legal challenges.
AB  - Ambient Intelligence provides the potential for vast and varied applications,
      bringing with it both promise and peril. The development of Ambient Intelligence
      applications poses a number of ethical and legal concerns. Mobile devices are
      increasingly evolving into tools to orientate in and interact with the
      environment, thus introducing a user-centric approach to Ambient Intelligence.
      The MINAmI (Micro-Nano integrated platform for transverse Ambient Intelligence
      applications) FP6 research project aims at creating core technologies for mobile
      device based Ambient Intelligence services. In this paper we assess five
      scenarios that demonstrate forthcoming MINAmI-based applications focusing on
      healthcare, assistive technology, homecare, and everyday life in general. A legal
      and ethical analysis of the scenarios is conducted, which reveals various
      conflicting interests. The paper concludes with some thoughts on drafting ethical
      guidelines for Ambient Intelligence applications.

PMID- 19597968
TI  - A rhetorical analysis of apologies for scientific misconduct: do they really mean
      it?
AB  - Since published acknowledgements of scientific misconduct are a species of image
      restoration, common strategies for responding publicly to accusations can be
      expected: from sincere apologies to ritualistic apologies. This study is a
      rhetorical examination of these strategies as they are reflected in choices in
      language: it compares the published retractions and letters of apology with the
      letters that charge misconduct. The letters are examined for any shifts in
      language between the charge of misconduct and the response to the charge in order
      to assess whether the apology was sincere or ritualistic. The results indicate
      that although most authors' published acknowledgments of scientific misconduct
      seem to minimize culpability by means of the strategic use of language, their
      resulting ritualistic apologies often still satisfy in some way the accusers'
      (and thus their community's) concerns.

PMID- 19597969
TI  - The Engineering and Science Issues Test (ESIT): a discipline-specific approach to
      assessing moral judgment.
AB  - To assess ethics pedagogy in science and engineering, we developed a new tool
      called the Engineering and Science Issues Test (ESIT). ESIT measures moral
      judgment in a manner similar to the Defining Issues Test, second edition, but is
      built around technical dilemmas in science and engineering. We used a quasi
      experimental approach with pre- and post-tests, and we compared the results to
      those of a control group with no overt ethics instruction. Our findings are that
      several (but not all) stand-alone classes showed a significant improvement
      compared to the control group when the metric includes multiple stages of moral
      development. We also found that the written test had a higher response rate and
      sensitivity to pedagogy than the electronic version. We do not find significant
      differences on pre-test scores with respect to age, education level, gender or
      political leanings, but we do on whether subjects were native English speakers.
      We did not find significant differences on pre-test scores based on whether
      subjects had previous ethics instruction; this could suggest a lack of a long
      term effect from the instruction.

PMID- 19597970
TI  - Effect of preparation conditions on the properties of bioactive glasses for
      testing SBF.
AB  - A simulated body fluid (SBF) with ion concentrations similar to body fluid,
      proposed by Kokubo et al., is widely used to evaluate bone-bonding potential
      through the formation of an apatite layer. To be confident of the evaluation of
      the potential for the apatite formation in SBF, standard substrates are required.
      Although Na(2)O-CaO-SiO(2) glasses have been focused upon as candidate standard
      substrates, it has not been clarified whether the preparation conditions of the
      glasses affect their apatite formation potential in SBF. In this study, Na(2)O
      CaO-SiO(2) glasses were prepared by a conventional melting-quenching method with
      different melting periods and annealing processes to examine their properties,
      including apatite formation in SBF. The Na(2)O-CaO-SiO(2) glasses show
      reproducible apatite-forming ability when prepared using moderate melting and
      annealing processes, and can be useful substrates to test the reproducibility of
      SBF.

PMID- 19597971
TI  - Degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate and
      polyethylenimine as a gene carrier: molecular weight of PEI affects transfection
      efficiency.
AB  - The aim of the research is to study the effect of polyethylenimine (PEI)
      molecular weight on the gene transfection efficiency of degradable poly(amino
      ester) based on poly(ethylene glycol) dimethacrylate (PEGDMA) and
      polyethylenimine (PEG-cr-PEI) as a gene carrier. Various low molecular weight
      (LMW) branched PEI based PEG-cr-PEI was synthesized via Michael addition. The
      degradation half-life of PEG-cr-PEI was longer at pH 5.6 than that at pH 7.4. The
      plasmid condensation and protection ability of the PEG-cr-PEI were confirmed by
      agarose gel electrophoresis assay. PEG-cr-PEI/DNA nanoparticles showed high
      positive zeta potential (>+20 mV), narrow size distribution, and spherical shapes
      with size below 250 nm when N/P ratios of PEG-cr-PEI to DNA were above 10,
      suggesting that they have endocytosis potential. The cytotoxicity of PEG-cr
      PEI/DNA complexes was lower than that of PEI 25K/DNA complexes, and the
      transfections mediated by PEG-cr-PEI were checked in 293T, HeLa and HepG2 cell
      lines. The report gene expression was increased with increasing the molecular
      weight of LMW PEI. The "proton sponge effect" was proposed as the mechanism of
      PEG-cr-PEI mediated gene transfection.

PMID- 19597972
TI  - Tumor characterization with dynamic contrast enhanced magnetic resonance imaging
      and biodegradable macromolecular contrast agents in mice.
AB  - PURPOSE: To investigate the efficacy of polydisulfide-based biodegradable
      macromolecular contrast agents of different degradability and molecular weight
      for tumor characterization based on angiogenesis using dynamic contrast enhanced
      MRI (DCE-MRI). METHODS: Biodegradable macromolecular MRI contrast agents, Gd-DTPA
      cystamine copolymers (GDCC) and Gd-DTPA cystine copolymers (GDCP), with molecular
      weight of 20 and 70 KDa were evaluated for tumor characterization. Gd(DTPA-BMA)
      and a prototype of macromolecular contrast agent, albumin-(Gd-DTPA), were used as
      controls. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and
      PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters
      including endothelium transfer coefficient (K(trans)) and fractional tumor plasma
      volume (f(PV)) were calculated from the DCE-MRI data using a two-compartment
      model and compared between the two different tumor models for each contrast
      agent. RESULTS: There was no significant difference in the f(PV) values between
      two tumor models estimated with the same agent except for GDCC-70. The K(trans)
      values in both tumor models decreased with the increase of molecular weight of
      contrast agents. With the same high molecular weight (70 KDa), GDCC-70 showed a
      higher K(trans) values than GDCP-70 due to high degradability of the former in
      both tumor models (p < 0.05). The K(trans) values of MDA PCa 2b tumors were
      significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC
      20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05). CONCLUSIONS: The
      polydisulfide-based biodegradable macromolecular MRI contrast agents are
      promising in tumor characterization and differentiation with dynamic contrast
      enhanced MRI.

PMID- 19597973
TI  - Depression among injured workers receiving vocational rehabilitation:
      contributions of work values, pain, and stress.
AB  - INTRODUCTION: Work-related injuries or disabilities result in significant
      negative consequences to physical, economic, social, and psychological well
      being. Depression has been shown to increase post-injury and to contribute to
      poor return to work outcomes. The primary goals of the study were to test known
      correlates of depression in a sample of injured workers receiving vocational
      rehabilitation and to assess the unique contribution of work values in injured
      worker depression. METHOD: Scores on depression, stress, pain, work values, and
      demographic information were obtained from an archived sample of 253 injured
      workers receiving vocational rehabilitation. RESULTS: Hierarchical multiple
      linear regression was used for analyses, resulting in a final model with a
      "large" effect size (R (2) = 0.42). The accepting vs. investigative work value
      dimension accounted for variance in depression scores beyond that accounted for
      by covariates and other significant correlates. Of the study variables,
      significant regression coefficients were found for pain, psychosocial stress, an
      interaction between pain and stress, and having an accepting work value.
      CONCLUSIONS: Injured workers experiencing higher levels of pain and stress and
      who prefer to avoid workplace challenges may be vulnerable to experiencing
      depression. Results suggest that the presence of pain, stress, and the accepting
      work value dimension should be monitored in injured workers, and that the role of
      work values in injured worker depression may be a fruitful area for further
      research.

PMID- 19597974
TI  - Extremely frequent behavior in consumer research: theory and empirical evidence
      for chronic casino gambling.
AB  - The present study informs understanding of customer segmentation strategies by
      extending Twedt's heavy-half propositions to include a segment of users that
      represent less than 2% of all households-consumers demonstrating extremely
      frequent behavior (EFB). Extremely frequent behavior (EFB) theory provides
      testable propositions relating to the observation that few (2%) consumers in many
      product and service categories constitute more than 25% of the frequency of
      product or service use. Using casino gambling as an example for testing EFB
      theory, an analysis of national survey data shows that extremely frequent casino
      gamblers do exist and that less than 2% of all casino gamblers are responsible
      for nearly 25% of all casino gambling usage. Approximately 14% of extremely
      frequent casino users have very low-household income, suggesting somewhat
      paradoxical consumption patterns (where do very low-income users find the money
      to gamble so frequently?). Understanding the differences light, heavy, and
      extreme users and non-users can help marketers and policymakers identify and
      exploit "blue ocean" opportunities (Kim and Mauborgne, Blue ocean strategy,
      Harvard Business School Press, Boston, 2005), for example, creating effective
      strategies to convert extreme users into non-users or non-users into new users.

PMID- 19597975
TI  - Thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me-gamma
      cyclodextrin: fluorescence, molecular mechanics and molecular dynamics.
AB  - The thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me
      gamma-cyclodextrin (XmgammaCD) in aqueous solution was studied by fluorescence
      techniques, Molecular Mechanics and Molecular Dynamics. Lifetime averages <tau>,
      obtained from fluorescence decay profiles upon excitation of the xylylene
      appended group, were used as the property sensitive to the association process.
      The dimerization equilibrium constants (K(D)) were obtained from non-linear
      regression analysis of the plots of <tau> against [XmgammaCD] at several
      temperatures and they were compared with the values obtained for the counterparts
      Xmalpha- and XmbetaCDs. The van't Hoff plot allows us to obtain the DeltaH and
      DeltaS showing that the dimerization process was also entropically disfavoured.
      Molecular Mechanics as well as Molecular Dynamics calculations in the presence of
      water were also employed to study the conformational behaviour of isolated
      XmgammaCDs, the possible structure of the dimers formed and the driving forces
      involved in such association processes. Results indicate that those conformations
      where Xy moiety does not block the cavity entrance are favoured. Dimers are
      preferably formed by head-to-head CD approaching. However, the formation of
      stable head-to-tail is not dismissed.

PMID- 19597978
TI  - Pharmacological preconditioning in type 2 diabetic rat hearts: the roles of
      mitochondrial ATP-sensitive potassium channels and the phosphatidylinositol 3
      kinase-Akt pathway.
AB  - PURPOSE: The authors examined whether olprinone, a phosphodiesterase type 3
      inhibitor, or isoflurane, a volatile anesthetic, could protect the heart against
      myocardial infarction in type 2 diabetic rats and whether the underlying
      mechanisms involve protein kinase C (PKC), mitochondrial ATP-sensitive potassium
      (m-K(ATP)) channels, or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway.
      METHODS: All rats underwent 30 min of coronary artery occlusion followed by 2 h
      of reperfusion. Wistar rats received isoflurane or olprinone before ischemia with
      or without the PKC inhibitor chelerythrine (CHE), the m-K(ATP) channel blocker 5
      hydroxydecanoic acid (5HD), or the PI3K-Akt inhibitor LY294002 (LY). Goto
      Kakizaki (GK) rats were randomly assigned to receive isoflurane or olprinone. In
      another group, GK rats received LY before the olprinone. RESULTS: In the Wistar
      rats, both isoflurane (38 +/- 11%) and olprinone (40 +/- 11%) reduced infarct
      size as compared to the control group (59 +/- 8%). In the GK rats, olprinone (41
      +/- 9%) but not isoflurane (53 +/- 11%) reduced infarct size as compared to the
      GK control group (58 +/- 14%). The beneficial effects of olprinone were blocked
      by LY (58 +/- 14%). In the Wistar rats, CHE, 5HD, and LY prevented isoflurane
      induced reductions of infarct size. On the other hand, LY but not CHE or 5HD
      prevented olprinone-induced reductions of infarct size. CONCLUSIONS: Olprinone
      but not isoflurane protects the heart against myocardial infarction in type 2
      diabetic rats. The olprinone-induced cardioprotective effect is mediated by the
      PI3K-Akt pathway but not PKC or m-K(ATP) channels.

PMID- 19597976
TI  - "Maybe I made up the whole thing": placebos and patients' experiences in a
      randomized controlled trial.
AB  - Patients in the placebo arms of randomized controlled trials (RCT) often
      experience positive changes from baseline. While multiple theories concerning
      such "placebo effects" exist, peculiarly, none has been informed by actual
      interviews of patients undergoing placebo treatment. Here, we report on a
      qualitative study (n = 27) embedded within a RCT (n = 262) in patients with
      irritable bowel syndrome. Besides identical placebo acupuncture treatment in the
      RCT, the qualitative study patients also received an additional set of interviews
      at the beginning, midpoint, and end of the trial. Interviews of the 12
      qualitative subjects who underwent and completed placebo treatment were
      transcribed. We found that patients (1) were persistently concerned with whether
      they were receiving placebo or genuine treatment; (2) almost never endorsed
      "expectation" of improvement but spoke of "hope" instead and frequently reported
      despair; (3) almost all reported improvement ranging from dramatic psychosocial
      changes to unambiguous, progressive symptom improvement to tentative impressions
      of benefit; and (4) often worried whether their improvement was due to normal
      fluctuations or placebo effects. The placebo treatment was a problematic
      perturbation that provided an opportunity to reconstruct the experiences of the
      fluctuations of their illness and how it disrupted their everyday life. Immersion
      in this RCT was a co-mingling of enactment, embodiment and interpretation
      involving ritual performance and evocative symbols, shifts in bodily sensations,
      symptoms, mood, daily life behaviors, and social interactions, all accompanied by
      self-scrutiny and re-appraisal. The placebo effect involved a spectrum of factors
      and any single theory of placebo--e.g. expectancy, hope, conditioning, anxiety
      reduction, report bias, symbolic work, narrative and embodiment--provides an
      inadequate model to explain its salubrious benefits.

PMID- 19597977
TI  - Direct measurement of energy fluxes from mitochondria into cytoplasm in
      permeabilized cardiac cells in situ: some evidence for Mitochondrial
      Interactosome.
AB  - The aim of this study was to measure energy fluxes from mitochondria in isolated
      permeabilized cardiomyocytes. Respiration of permeabilized cardiomyocytes and
      mitochondrial membrane potential were measured in presence of MgATP, pyruvate
      kinase - phosphoenolpyruvate and creatine. ATP and phosphocreatine concentrations
      in medium surrounding cardiomyocytes were determined. While ATP concentration did
      not change in time, mitochondria effectively produced phosphocreatine (PCr) with
      PCr/O(2) ratio equal to 5.68 +/- 0.14. Addition of heterodimeric tubulin to
      isolated mitochondria was found to increase apparent Km for exogenous ADP from 11
      +/- 2 microM to 330 +/- 47 microM, but creatine again decreased it to 23 +/- 6
      microM. These results show directly that under physiological conditions the major
      energy carrier from mitochondria into cytoplasm is PCr, produced by mitochondrial
      creatine kinase (MtCK), which functional coupling to adenine nucleotide
      translocase is enhanced by selective limitation of permeability of mitochondrial
      outer membrane within supercomplex ATP Synthasome-MtCK-VDAC-tubulin,
      Mitochondrial Interactosome.

PMID- 19597979
TI  - Twins with KBG syndrome and autism.

PMID- 19597980
TI  - Characterization of a newly emerged genetic cluster of H1N1  and H1N2 swine
      influenza virus in the United States.
AB  - H1 influenza A viruses that were distinct from the classical swine H1 lineage
      were identified in pigs in Canada in 2003-2004; antigenic and genetic
      characterization identified the hemagglutinin (HA) as human H1 lineage. The
      viruses identified in Canadian pigs were human lineage in entirety or double
      (human-swine) reassortants. Here, we report the whole genome sequence analysis of
      four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four
      isolates were characterized as triple reassortants with an internal gene
      constellation similar to contemporary U.S. swine influenza virus (SIV), with HA
      and neuraminidase (NA) most similar to human influenza virus lineages. A 2007
      human-like H1N1 was evaluated in a pathogenesis and transmission model and
      compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The
      2007 isolate induced disease typical of influenza virus and was transmitted to
      contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1
      SIV. This study indicates that the human-like H1 SIV can efficiently replicate
      and transmit in the swine host and now co-circulates with contemporary SIVs as a
      distinct genetic cluster of H1 SIV.

PMID- 19597981
TI  - Expansion of CAG repeats in the spinocerebellar ataxia type 1 (SCA1) gene in
      idiopathic oligozoospermia patients.
AB  - PURPOSE: The lengths of CAG repeats in two spinocerebellar ataxia genes, SCA1 and
      SCA3, were analyzed to determine whether such repeats exist in higher numbers in
      infertile males. METHODS: Blood samples were collected from healthy controls,
      oligozoospermia patients, and azoospermia patients. DNA fragments containing
      target CAG repeats were amplified by PCR with template DNA purified from the
      blood samples. CAG repeats in PCR fragments were determined, using ABI PRISM 310
      Gene Analyzer. RESULTS: In SCA1, the distribution of CAG repeats in
      oligozoospermic males was different from that of the control group: More alleles
      had a repeat number that exceeded 32. Conversely, for SCA3, the examined
      oligozoospermia and azoospermia patients exhibited no differences in distribution
      of CAG repeats in comparison with the control group. CONCLUSIONS: SCA1 in a
      subset of oligozoospermia patients has an increased number of CAG repeats.

PMID- 19597982
TI  - A theoretical model for single blastocyst transfer.
AB  - OBJECTIVE: To elucidate the relationship between embryo grade and ART outcomes
      and determine how to decrease multiple pregnancy rates by assigning patients to
      single embryo transfer (SET) instead of dual embryo transfer (DET) according to
      embryo grade and/or availability. DESIGN: Retrospective medical record review.
      SETTING: IVF fertility center. PATIENTS: 247 women undergoing day 5 DET after in
      vitro fertilization or intracytoplasmic sperm injection treatment. METHODS: We
      retrospectively investigated embryo grade and outcomes on day 5 DET and
      calculated theoretical multiple pregnancy rates by assigning patients to SET
      instead of DET according to a combination of embryo grades and availability. MAIN
      OUTCOMES MEASURES: Implantation, pregnancy, multiple pregnancy, expected
      pregnancy and expected multiple pregnancy rates. RESULTS: Embryo grade affects
      implantation rates so that embryo transfer of at least one embryo with grade > or
      = 3BB resulted in high multiple pregnancy rates as well as high pregnancy rates.
      By performing DET, the clinical pregnancy rate was 39.9% with a multiple
      pregnancy rate of 33.3%; however, had SET been performed with an embryo graded
      3BB or better, theoretical calculated pregnancy rates would have dropped to 35.8%
      but with a multiple pregnancy rate of 7.2%. CONCLUSIONS: Our model showed that
      cases having at least one embryo with grade > or = 3BB might serve as suitable
      candidates for SET.

PMID- 19597984
TI  - Addressing the challenges faced by early adolescents: a mixed-method evaluation
      of the benefits of peer support.
AB  - In this article, we describe a mixed-methods study used to examine the
      effectiveness of a widely-used peer support program designed to facilitate the
      transition to adolescence and high school by enhancing self-concept and other
      desirable outcomes. For the quantitative component, a longitudinal design was
      employed (930 Grade 7 students, 3 schools, 2 years), with control group and
      baseline (i.e., pre-program) data against which to compare the effects. Using a
      multilevel approach, the results provide evidence to suggest that the program was
      largely successful in achieving its aims of enhancing students' school self
      concept, school citizenship, sense of self and possibility, connectedness, and
      resourcefulness. A sub-sample of students from the experimental group
      participated in the qualitative component, which included open-ended survey
      results (n = 408 Grade 7 students, n = 75 peer support leaders) and focus groups
      (n = 119 Grade 7 students, n = 44 peer support leaders) to identify students'
      personal perspectives of the program. The qualitative results confirmed the
      quantitative findings that the program has important benefits for Grade 7
      students and provided rich and valuable insights into students' views of the
      intervention. The findings of this research have important implications and
      suggest that the provision of peer support has the potential to a make
      significant contribution to schools' efforts to orchestrate positive outcomes for
      adolescents.

PMID- 19597983
TI  - Allele frequency distribution data for D8S1132, D8S1779, D8S514, and D8S1743 in
      four ethnic groups in relation to metabolic syndrome: Tehran Lipid and Glucose
      Study.

PMID- 19597985
TI  - Impact of obesity on diagnosis and treatment of breast cancer.
AB  - In this population-based study, we evaluated the impact of obesity on
      presentation, diagnosis and treatment of breast cancer. Among all women diagnosed
      with invasive breast cancer in the canton Geneva (Switzerland) between 2003 and
      2005, we identified those with information on body mass index (BMI) and
      categorized them into normal/underweight (BMI <25 kg/m(2)), overweight (BMI > or
      =-<30 kg/m(2)) and obese (BMI > or =30 kg/m(2)) women. Using multivariate
      logistic regression, we compared tumour, diagnosis and treatment characteristics
      between groups. Obese women presented significantly more often with stage III-IV
      disease (adjusted odds ratio [OR(adj)]: 1.8, 95% CI: 1.0-3.3). Tumours > or =1 cm
      and pN2-N3 lymph nodes were significantly more often impalpable in obese than in
      normal/underweight patients (OR(adj) 2.4, [1.1-5.3] and OR(adj) 5.1, [1.0-25.4],
      respectively). Obese women were less likely to have undergone ultrasound (OR(adj)
      0.5, [0.3-0.9]) and MRI (OR(adj) 0.3, [0.1-0.6]) and were at increased risk of
      prolonged hospital stay (OR(adj) 4.7, [2.0-10.9]). This study finds important
      diagnostic and therapeutic differences between obese and lean women, which may
      impair survival of obese women with breast cancer. Specific strategies are needed
      to optimize the care of obese women with or at risk of breast cancer.

PMID- 19597987
TI  - An integrated approach to determine sediment quality in areas above CO2 injection
      and storage in agreement with the requirements of the international conventions
      on the protection of the marine environment.
AB  - The urgent need to reduce the greenhouse emissions to the atmosphere has leaded
      to study new systems to capture and store carbon dioxide (CO(2)). The
      sequestration of CO(2) in marine geological formations is one of these systems
      proposed at the international level to effectively reduce the concentration of
      atmospheric CO(2). Although permanent containment is expected, it is necessary to
      determine the risk of leakage to the marine environment. The integrated model for
      the evaluation of the environmental quality of the marine environment will
      contribute to determine the potential environmental pathways and effects that are
      relevant to the consideration of the potential consequences of the leakage of
      CO(2) and incidental associated substances from the geological formations to the
      marine environment. In addition, this model will satisfy the requirements for a
      safe CO(2) storage in sub-seabed geological formations set in the international
      conventions on the protection of the marine environment (1992 OSPAR Convention
      and 1996 London Protocol). The objective of this paper is to show how to adapt
      classical methodologies based on a weight-of-evidence approach to establish the
      impact of CO(2) leaks in the sediment quality. It is described how the classical
      methods should modify their application when acidification occurs related to
      CO(2) leaks being the main potential impact in these areas.

PMID- 19597986
TI  - Oral contraceptives and postmenopausal hormones and risk of contralateral breast
      cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study.
AB  - The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH)
      use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation
      carriers with a history of breast cancer. We investigated the association between
      OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE
      (Women's Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study
      is a population-based case-control study of 705 women with asynchronous CBC and
      1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation
      carriers. Risk-factor information was assessed by telephone interview. Mutation
      status was measured using denaturing high-performance liquid chromatography
      followed by direct sequencing in all participants. Outcomes, treatment, and tumor
      characteristics were abstracted from medical records. Ever use of OCs was not
      associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66-1.15) or BRCA2
      carriers (RR = 0.82; 95% CI = 0.21-3.13). BRCA1 carriers who used OCs had a
      nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72-7.83). Total
      duration of OC use and at least 5 years of use before age 30 were associated with
      a nonsignificant increased risk among mutation carriers but not among
      noncarriers. Few women had ever used PMH and we found no significant associations
      between lifetime use and CBC risk among carriers and noncarriers. In conclusion,
      the association between OC/PMH use and risk of CBC does not differ significantly
      between carriers and noncarriers; however, because carriers have a higher
      baseline risk of second primaries, even a potential small increase in risk as a
      result of OC use may be clinically relevant.

PMID- 19597988
TI  - Toxicity of copper in natural marine picoplankton populations.
AB  - Standard microalgae toxicity tests should be able to establish responses in real
      ecosystems. Natural marine picoplankton samples collected during the months of
      March, June, August, October 2007 and January 2008, where exposed to 72 h copper
      toxicity tests. Results analysed by flow cytometry distinguished two groups, with
      different cytometric characteristics that can match with two of Synechococcus
      populations. EC(50) values for these two populations resulted low, ranging from
      0.62 to 26.28 microg L(-1), this converts copper in a very powerful contaminant
      and Synechococcus in one of the most sensitive groups of phytoplankton.
      Differences in EC(50) values for a same population can be related to the month of
      collection including different initial cellular densities and oceanographic
      parameters that can affect the picoplankton's tolerance and distribution.

PMID- 19597989
TI  - Ecological risk assessment of sediment management areas: application to Sado
      Estuary, Portugal.
AB  - The purpose of this work was to integrate different methodologies to assess the
      potential ecological risk of estuarine sedimentary management areas, using the
      Sado Estuary in Portugal as case study. To evaluate the environmental risk of
      sediment contamination, an integrative and innovative approach was used involving
      assessment of sediment chemistry, sediment toxicity, benthic community structure,
      human driving forces and pressures and management areas organic load levels. The
      basis for decision-making for overall assessment was a statistical multivariate
      analysis appended into a score matrix tables, using a best expert judgment. The
      integrated approach allowed to identify from the 19 management areas analyzed,
      three with no risk but other three with high risk to cause adverse effects in the
      biota, related with the contaminants analyzed. The methodologies used showed to
      be effective as a support for decision making leading to future estuarine
      management recommendations.

PMID- 19597990
TI  - Influence of Pseudomonas putida AF7 inoculation on soil enzymes.
AB  - There has been some concern about the environmental impact of microbial agents.
      Pseudomonas may be used as bioremediator and as biopesticide. In this study, we
      report the use of soil enzyme assays as biological indicator of possible negative
      effects in soil functioning after the P. putida AF7 inoculation. For that, P.
      putida AF7 was originally isolated from the rizosphere of rice and was inoculated
      on three soil types: Rhodic Hapludox (RH), Typic Hapludox (TH); and Arenic
      Hapludult (AH). The acid phosphatase, beta-glucosidase and protease enzymes
      activities were measured for three period of evaluation (7, 14 and 21 days). In
      general, the enzymatic activities presented variation among the tested soils. The
      highest activities of beta-glucosidase and acid phosphatase were observed in the
      RH and AH soils, while the protease activity was higher in the TH soil. Also, the
      soil characteristics were measured for each plot. The activity of enzymes from
      the carbon cycle was positively correlated with the N and the P and the enzyme
      from the nitrogen cycle was negatively correlated with N and C.org. The presented
      data indicate that soil biochemical properties can be an useful tool for use as
      an indicator of soil perturbations by microbial inoculation in a risk assessment.

PMID- 19597991
TI  - Stress responses of Erica andevalensis Cabezudo & Rivera plants induced by
      polluted water from Tinto River (SW Spain).
AB  - The effects of Tinto River water on Erica andevalensis growth, biochemical
      indicators and elemental concentration and distribution were investigated under
      laboratory conditions. High levels of toxic elements such as B, Fe and S and
      acidic pH characterized the river water. Plant analysis revealed that the
      concentration of Al, B, S and Fe increased in all plant organs reaching in some
      cases values in the toxicity range. Plants transferred into river water stopped
      growing and stress was manifested by plant water loss, increase in peroxidase
      activity and decrease of chlorophyll a concentration. Significant decreases of
      free amino acid concentration were found in shoots and roots of plants grown in
      diluted river water. The results indicated that Tinto River water acidity and its
      excess in soluble elements produced altogether severe alterations in roots
      affecting plant water and nutrient uptake and leading to the massive entry of
      some metals (e.g. Fe, Al) with toxic effects. Scanning-electron microscopy
      (cryoSEM and ESEM) observations showed that E. andevalensis had not exclusion
      mechanisms of Cu, Fe and S therefore it was not able to reduce translocation to
      aerial parts.

PMID- 19597992
TI  - Comorbidity between psychiatric and general medical disorders in homeless
      veterans.
AB  - Homeless veterans have numerous co-occurring medical and behavioral health
      problems. Identification of common patterns of comorbid conditions may help
      providers to determine severity of medical conditions and triage health care more
      effectively. In this study we identify such patterns of comorbid medical and
      psychiatric disorders using cluster analysis and we evaluate relationships
      between these patterns and sociodemographic factors. We used data from a survey
      of 3,595 veterans in a regional VA network who were presently or recently
      homeless assessing nine major medical disorder and six psychiatric disorder
      categories. Diagnostic ratings of presence or absence of these disorders were
      placed into the same cluster analysis to determine whether separable clusters
      emerged reflecting differing diagnostic profiles. There are recognizable patterns
      of comorbidity involving several psychiatric and general medical disorders, as
      well as disorders of both types that exist independently. Cluster membership was
      associated with various sociodemographic indices. Mental and general medical
      health problems in homeless veterans often occur in association with each other
      and form identifiable patterns that vary on sociodemographic factors.

PMID- 19597993
TI  - Analysis of surface atrial signals: time series with missing data?
AB  - Uncovering of the atrial signal for patients undergoing episodes of atrial
      fibrillation is usually obtained from surface ECG by removing waves induced by
      ventricular activities. Once earned the atrial signal, the detection of the
      dominant fibrillation frequency is often the main (and only) goal. In this work
      we verified if subtraction of the ventricular activity might be avoided by
      performing spectral analysis on those ECG segments where ventricular activity is
      absent, (i.e. the T-Q intervals). While the approach might seem crude, in here
      the question was recast into a problem of missing data in a long time series and
      proper methods were applied: the Lomb periodogram and the iterative Singular
      Spectrum Analysis. The two methods were tested on both simulated signals and
      "realistic" atrial signals constructed using the ECG recordings provided by the
      2004 Computers in Cardiology competition. The results obtained showed that both
      techniques were able to provide a reliable quantification of the dominant
      oscillation, with a slightly superior performance of the iterative Singular
      Spectrum Analysis. Absolute errors larger than 1.0 Hz were unlikely (p < 0.05) up
      to 130-140 bpm. Such level of agreement is consistent with similar comparative
      works where techniques for separating the atrial signal from ventricular waves
      were considered.

PMID- 19597994
TI  - Finger-actuated, self-contained immunoassay cassettes.
AB  - The building blocks for an inexpensive, disposable, luminescence-based
      microfluidic immunoassay cassette are described, and their integration in a point
      of-care diagnostic system is demonstrated. Fluid motion in the cassette is driven
      by depressing finger-actuated pouches. All reagents needed for the immunoassay
      can be stored in the cassette in liquid form. Prior to use, the cassette consists
      of two separate parts. A top storage component contains pouches, sealed storage
      chambers, a metering chamber, and needle seats. The bottom processing component
      contains connection needles, a mixing chamber, and a detection chamber with
      immobilized proteins. Subsequent to sample introduction, the storage and
      processing components are mated. The needles form hydraulic connections between
      the two parts and, in some cases, close valves. The pouches are then actuated
      sequentially to induce flow of various reagents and facilitate process
      operations. The cassette is compatible with different detection modalities. Both
      a cassette with immunochromatographic-based detection and a cassette with
      microbead-based detection were constructed and evaluated. The
      immunochromatographic cassette was used to detect antibodies to HIV in saliva
      samples. The bead-based cassette was used to detect the proinflammatory chemokine
      IL-8. The experimental data demonstrates good repeatability and reasonable
      sensitivity.

PMID- 19597995
TI  - Cancer prevention behaviors in low-income urban whites: an understudied problem.
AB  - Low-income urban whites in the United States have largely gone unexamined in
      health disparities research. In this study, we explored cancer prevention
      behaviors in this population. We compared data on whites with low socioeconomic
      status (SES) from the 2003 Exploring Health Disparities in Integrated Communities
      Study in Southwest Baltimore, Maryland (EHDIC-SWB) with nationally representative
      data for low SES white respondents from the 2003 National Health Interview Survey
      (NHIS). Rates for health behaviors and health indicators for whites from the
      EHDIC-SWB study as compared to NHIS prevalence estimates were as follows: current
      cigarette smoking, 59% (31% nationally); current regular drinking, 5% (5%
      nationally); overweight, 26% (32% nationally); obesity, 30% (22% nationally);
      mammography in the past 2 years, 50% (57% nationally); Pap smear in the past 2
      years, 64% (68% nationally); screening for colon cancer in the past 2 years, 41%
      (30% nationally); and fair or poor self-reported health, 37% (22% nationally).
      Several cancer prevention behaviors and health indicators for white EHDIC-SWB
      respondents were far from the Healthy People 2010 objectives. This study provides
      rare estimates of cancer-related health and health care measures in an
      understudied population in the United States. Findings illustrate the need for
      further examination of health behaviors in low SES white urban populations who
      may share health risks with their poor minority urban counterparts.

PMID- 19597996
TI  - Worldwide stress: different problems, similar solutions? Cultural adaptation and
      evaluation of a standardized stress management program in Hungary.
AB  - BACKGROUND: Chronic stress is an important risk factor for morbidity and
      premature mortality at the individual and societal level. PURPOSE: Our aim was to
      describe the process of adapting and testing the effectiveness of a structured
      stress management skills training program in a culture different from the one in
      which it was first developed. METHOD: We translated an internationally used
      standardized behavioral intervention program into Hungarian and adapted it for
      use in a Hungarian cultural setting. We evaluated the changes in stress level and
      stress-related symptom scores among distressed voluntary participants on the
      basis of self-reported questionnaires completed before, immediately after, and 4
      to 6 months after the 12-h intervention. The following measures were included:
      PSS-10, STAI-T, BDI-S, PHQ-15, and WBI-5. For statistical analyses, paired sample
      t test and Cohen's d value for effect size were used. RESULTS: In a sample of 107
      distressed individuals, after the training, stress level, psychological and
      somatic symptoms decreased and well-being increased (p < 0.0001). These positive
      changes were maintained at follow-up in a subsample of 42 persons tested 4-6
      months later. CONCLUSION: These results confirm the long-term positive effects of
      this standardized behavioral intervention in a different cultural context and in
      real-world settings, which encourages further dissemination of the program in
      various community settings.

PMID- 19597997
TI  - Concordance between self-reported and objective wakeup times in ambulatory
      salivary cortisol research.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis functioning has
      implications for physical and mental health. One important indicator of HPA axis
      functioning, the salivary cortisol awakening response (CAR), is sensitive to
      whether participants provide their samples at the requested times after waking.
      PURPOSE: To examine the extent to which adolescents report morning wakeup times
      accurately, test the impact of inaccurate waketime reporting on compliance with a
      salivary cortisol sampling protocol designed to estimate the CAR, and to examine
      the implications of non-compliance for CAR estimates. METHOD: In a sample of 91
      late adolescents, objective waketimes determined using actigraphy were compared
      to self-reported waketimes. Associations between accuracy of waketimes and
      compliance with requested morning cortisol sampling timings (wakeup and 30 min
      post-awakening) were examined, as were implications of non-compliance for the
      size of the CAR. RESULTS: In terms of accuracy, 72% of self-reported waketimes
      were within 5 min and 90% were within 15 min of objective waketimes. Individuals
      who were more than 5 min discrepant in their waketime reporting, however, had a
      90% decrease in their likelihood of being compliant-taking both morning cortisol
      samples within the requested time frames after waking. However, CARs were
      significantly lower only among individuals whose subjective and objective
      waketimes differed by more than 15 min. CONCLUSIONS: Self-reported waketimes were
      reasonably accurate when compared to objective estimates of time of waking. When
      available, however, estimates of compliance are improved by knowledge of
      objective waketimes, resulting in increased accuracy of CAR estimates.

PMID- 19597999
TI  - Single-chain Fv antibody fragments retain binding properties of the monoclonal
      antibody raised against peptide P1 of the human prion protein.
AB  - Prion diseases are incurable neurodegenerative diseases that affect both humans
      and animals. The infectious agent is a pathogenic form of the prion protein that
      accumulates in brain as amyloids. Currently, there is neither cure nor reliable
      preclinical diagnostics on the market available. The growing number of reports
      shows that passive immunisation is one of the most promising strategies for prion
      disease therapy, where antibodies against prions may prevent and even cure the
      infection. Since antibodies are large molecules and, thus, might not be suitable
      for the therapy, different antibody fragments are a good alternative. Therefore,
      we have designed and prepared single-chain antibody fragments (scFvs) derived
      from the PrP(Sc)-specific murine monoclonal antibody V5B2. Using a new expression
      vector pMD204, we produced scFvs in two opposing chain orientations in the
      periplasm of Escherichia coli. Both recombinant antibody fragments retained the
      specificity of the parent antibody and one of these exhibited binding properties
      comparable to the corresponding murine Fab fragments with the affinity in nM
      range. Our monovalent antibody fragments are of special interest in view of
      possible therapeutic reagents for prion diseases as well as for development of a
      new generation of diagnostics.

PMID- 19597998
TI  - The contribution of direct TLR signaling to T cell responses.
AB  - It is well established that Toll-like receptors (TLRs) play a critical role in
      the generation of innate immune responses and thereby also play an important,
      indirect role in the initiation of subsequent adaptive T cell responses. However,
      T cells also express certain TLRs, and we have focused on the physiological
      importance of direct TLR signaling in T cells. TLRs can function as co
      stimulatory receptors that complement TCR-induced signals to enhance effector T
      cell proliferation, survival and cytokine production. We also found that TLR
      signaling pathways in T cells are required for the effective clonal expansion of
      antigen-specific T cells during infection in vivo. Thus, the importance of TLRs
      in T cell-mediated immunity reflects both T cell-extrinsic and T cell-intrinsic
      components, which warrants a reconsideration of the dogma that restricts germ
      line encoded pattern recognition to cells of the innate immune system.

PMID- 19598000
TI  - L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP
      production in vitro.
AB  - L-PGDS is the most abundant protein present in the cerebrospinal fluid (CSF).
      Although CSF was believed to be homogenous in content, a previous study has
      showed that a marked concentration gradient of L-PGDS exists between the spinal
      CSF and the CSF in the subarachnoid space of patients with optic nerve disease
      (papilledema and normal-tension glaucoma). Astrocytes play a critical role in
      maintaining the integrity of axon function in the central nervous system and
      specifically in the optic nerve, and we therefore investigated the biochemical
      effects of L-PGDS on the proliferation of astrocytes and on the production of
      adenosine triphosphate (ATP) by astrocyte mitochondria. We found an inhibitory
      effect of L-PGDS on both proliferation of astrocytes and production of astrocyte
      ATP. The concentrations that inhibited astrocyte proliferation and ATP production
      were in the range measured in patients with idiopathic intracranial hypertension
      and in patients with normal-tension glaucoma. As the CSF is in contact with axons
      and mitochondria of the optic nerve (Bristow et al. Archives of Ophthalmology,
      120, 791-796, 2002), we postulate that a change in the concentration of CSF
      protein such as L-PGDS could exercise a harmful effect on these structures.

PMID- 19598001
TI  - Extra-adrenal composite paraganglioma with ganglioneuroma component presenting as
      a pancreatic mass.
AB  - Paragangliomas may have composite forms in which they combine features of a
      typical paraganglioma with those of a neural component consisting of either
      neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. These variants are rare
      and generally located in the adrenal. Herein, we describe a retroperitoneal,
      extra-adrenal composite paraganglioma-ganglioneuroma of a 57-year-old woman.
      Radiological evaluation revealed a nodular mass with apparent pancreatic
      location, with findings suggestive of an endocrine tumor, yielding the diagnosis
      of a pancreatic endocrine tumor. At histology the neoplasm, strictly adhering to
      the external surface of the pancreatic gland but well demarcated, displayed a
      main central region with typical paraganglioma features and cells arranged in
      cords and in a nesting "zellballen" pattern, positive for neuroendocrine markers,
      and a distinct peripheral area consisting of dense bundles of wavy spindled
      Schwann cells, with scattered ganglionic cells.

PMID- 19598003
TI  - Ectopic mediastinal parathyroid adenoma: a cause of acute pancreatitis.
AB  - A 38-year-old male was admitted to our hospital with epigastric pain, and he was
      confirmed to have acute exudative pancreatitis. After the episode of acute
      pancreatitis subsided, laboratory investigation revealed increased serum calcium
      (12.0 mg/dl), decreased serum phosphorus (2.7 mg/dl), and increased serum
      parathyroid hormone (intact) levels (131 pg/ml). A computed tomography (CT) scan
      of the neck did not reveal any mass lesions in the parathyroid gland. However,
      (99m)Tc sestamibi scintigraphy revealed that there was one functioning
      parathyroid gland in the upper mediastinum. Combined (99m)Tc sestamibi
      scintigraphy and CT scan confirmed the diagnosis of primary hyperparathyroidism
      in the mediastinum. Microscopic examination revealed the presence of a
      parathyroid adenoma (1.3 x 0.4 cm(2)) adjacent to the atrophic parathyroid gland
      in right thymus gland. We report the case of a patient diagnosed with primary
      hyperparathyroidism due to an ectopic mediastinal parathyroid adenoma. An ectopic
      mediastinal parathyroid adenoma may manifest as an episode of acute pancreatitis.
      Preoperative investigation to determine the exact location of an adenoma should
      include two types of imaging studies, preferably (99m)Tc sestamibi scintigraphy
      and CT of the neck and chest.

PMID- 19598002
TI  - MicroRNAs in adult and embryonic neurogenesis.
AB  - Neurogenesis is defined as a process that includes the proliferation of neural
      stem/progenitor cells (NPCs) and the differentiation of these cells into new
      neurons that integrate into the existing neuronal circuitry. MicroRNAs (miRNAs)
      are a recently discovered class of small non-protein coding RNA molecules
      implicated in a wide range of diverse gene regulatory mechanisms. More and more
      data demonstrate that numerous miRNAs are expressed in a spatially and temporally
      controlled manners in the nervous system, which suggests that miRNAs have
      important roles in the gene regulatory networks involved in both brain
      development and adult neural plasticity. This review summarizes the roles of
      miRNAs-mediated gene regulation in the nervous system with focus on neurogenesis
      in both embryonic and adult brains.

PMID- 19598004
TI  - Association of arterial stiffness with HbA1c in 1,000 type 2 diabetic patients
      with or without hypertension.
AB  - The objective is to evaluate the association of arterial stiffness [brachial
      ankle pulse wave velocity (ba-PWV)] with glycemic control and duration of type 2
      diabetes in diabetic subjects with or without hypertension. One thousand Chinese
      diabetic patients (562 with hypertension, 438 without hypertension) were included
      in this study. All patients underwent ba-PWV and biochemical measurements. Ba-PWV
      was significantly higher in diabetic subjects with hypertension than those
      without hypertension (1779 +/- 341 vs. 1691 +/- 342 cm/s, P < 0.0001), and these
      subjects were under similar glycemic control (6.9 +/- 1.5 vs. 6.9 +/- 1.3, P =
      0.86). In diabetic and hypertensive subjects, ba-PWV was positively associated
      with HbA1c (1715 +/- 314 vs. 1851 +/- 335 cm/s, in subjects with HbA1c < 6.5% and
      with HbA1c > 7.0%, respectively, P < 0.0001), as well as duration of diabetes
      (1671 +/- 342 vs. 1791 +/- 313 vs. 1861 +/- 338 cm/s, in subjects with duration
      of diabetes <5 years, 5-10 years, and >10 years, respectively, P all < 0.05). In
      diabetic subjects without hypertension, ba-PWV was not associated with HbA1c (P =
      0.47), but associated with duration of diabetes (1503 +/- 272 vs. 1692 +/- 354
      cm/s, in subjects with duration of diabetes <5 years and >10 years, respectively,
      P = 0.0013). Ba-PWV was higher in diabetic subjects with hypertension than in
      diabetic subjects without hypertension, suggesting the independent effect of
      hypertension on arterial stiffness in diabetic subjects. Ba-PWV positively
      correlated with HbA1c and duration of diabetes in subjects with diabetes and
      hypertension, suggesting the importance of early glycemic control in the
      prevention of arterial stiffness and vascular complications.

PMID- 19598005
TI  - Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as
      a novel risk factor for diabetic nephropathy.
AB  - Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction
      and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a
      significant increase at plasma homocysteine levels. In this study we aimed to
      evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia
      on the development of diabetic microvascular complications in comparison with the
      other defined risk factors. Diabetic patients without a history of macrovascular
      complication or overt nephropathy enrolled into the study. The presence of MTHFR
      677 C-T point mutation was evaluated by Real-Time PCR technique by using a
      LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52.
      Patients with diabetes were divided into two groups according to the presence of
      MTHFR gene mutation. Both groups were well matched regarding age and diabetes
      duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic
      acid, and vitamin B12 levels were also studied. Presence of neuropathy and
      retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic
      and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not
      different between the two groups. Plasma homocysteine (12.89 +/- 1.74 and 8.98 +/
      1.91 micromol/l; P < 0.0001) and microalbuminuria levels (73.40 +/- 98.15 and
      29.53 +/- 5.08 mg/day; P = 0.021) were significantly higher in the group with
      MTHFR gene mutation while creatinine clearance levels (101.1 +/- 42.6 and 136.21
      +/- 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of
      the patients with diabetic nephropathy had MTHFR gene mutation, while this was
      only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a
      significant correlation of plasma homocysteine level with microalbuminuria (r =
      0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T
      polymorphism. We did not find any specific association of MTHFR gene mutation and
      hyperhomocysteinemia with retinopathy or neuropathy.

PMID- 19598007
TI  - Comparison of composite whole body insulin sensitivity index derived from mixed
      meal test and oral glucose tolerance test in insulin resistant obese subjects.
AB  - Apart from fasting blood glucose (FBG) and insulin (FBI), oral glucose tolerance
      test (OGTT) is also used in calculating insulin sensitivity. During OGTT, insulin
      secretion may not reflect normal physiological insulin secretion. Based on this
      idea, hepatic and whole body insulin sensitivity rates were tested during OGTT
      and mixed meal test (MMT) in obese subjects. Thirty-one women with Quantitative
      Insulin Sensitivity Check Index (QUICKI) values below 0.350 and body mass index
      (BMI) >or=30 were included into the study. OGTT with 75-g glucose and MMT 300
      kcal were applied to all cases. Data obtained from OGTT and MMT were used in the
      assessment of insulin sensitivity with Hemostasis of Model Assessment-Insulin
      Resistance (HOMA-IR) and Matsuda's Composite Whole Body Insulin Sensitivity Index
      (Matsuda's ISI). Mean BMI, FBG, and FBI were 36.8 +/- 3.9 kg/m(2), 100.5 +/- 0.10
      mg/dl, 16.2 +/- 5.3 microg/ml, respectively. QUICKI was 0.31 +/- 0.01 and HOMA-IR
      was 3.71 +/- 0.88. Matsuda's ISI derived from OGTT was 6.96 +/- 3.35 and from MMT
      was 11.32 +/- 6.61. In analysis, it was demonstrated that there was a correlation
      between HOMA-IR, QUICKI, and Matsuda's ISIs derived from OGTT and MMT. Comparing
      the time periods separately, it was detected that despite similar increment in
      insulin levels, glucose levels were higher in OGTT than MMT at 15 and 30 min.
      Consequently, Matsuda's ISI was demonstrated to be effectively used with the data
      of MMT, as used with OGTT. Moreover, MMT was shown to be in parallel to
      physiologic insulin secretion and reflect pancreatic functions better compared to
      OGTT.

PMID- 19598006
TI  - Uncoupling protein-3 as a molecular determinant of the action of 3,5,3'
      triiodothyronine on energy metabolism.
AB  - Thyroid hormones are known to stimulate thermogenesis in rodents by exerting a
      permissive effect on norepinephrine that affects uncoupling protein-1 (UCP1)
      expression in brown adipose tissue (BAT). The aim of this study was to identify
      new targets of the thermogenic effects of T3 in tissues other than the BAT, such
      as skeletal muscle. In beta(1)/beta(2)/beta(3)-adrenoceptor knockout (beta-less)
      mice, that are dramatically cold intolerant, a normal body temperature was
      maintained throughout 48 h of cold exposure by T3 administration. In these mice,
      BAT UCP1 protein expression was not modified either by cold exposure or by T3
      administration. To test the possibility that T3 might act via muscle uncoupling
      protein-3 (UCP3), an UCP3 knockout (KO) model was used. This model exhibited a
      normal phenotype except that, upon T3 administration, stimulated oxygen
      consumption of the UCP3KO mice was significantly lower by 6% than that of the
      wild-type (WT) mice. This difference was observed only during the dark period
      (between 7.00 p.m. and 7.00 a.m.), i.e. when the mice are the most active at
      consuming food. Therefore, UCP3 might participate in the correction by T3 of the
      dramatic cold intolerance of the beta-less mice. These results reactivate the
      idea that UCP3 might play a role in the control of energy balance.

PMID- 19598008
TI  - Biochemical effects of calcifediol supplementation in mild, asymptomatic,
      hyperparathyroidism with concomitant vitamin D deficiency.
AB  - It has been proposed to cautiously supplement with vitamin D to any patient with
      asymptomatic primary hyperparathyroidism (PHTP) and a plasma 25-hydroxyvitamin D
      [25(OH)D] concentration <50 nmol/l. Evidence about the safeness of this
      intervention is limited to two studies. Our aim was to prospectively assess the
      biochemical effects of one-year 25(OH)D supplementation in this context. Twenty
      seven patients were included in this study. Calcifediol was started at a dose of
      480-960 IU/24 h (8-16 microg/24 h) and adjusted up to a maximum of 960 IU/24 h
      (16 microg/24 h). Basal calcium, phosphate, albumin, total alkaline phosphatase
      (ALP), creatinine, 24 h calcium urinary excretion, intact PTH (iPTH) and 25(OH)D
      were measured before and during vitamin D supplementation. The mean basal 25(OH)D
      was 28.7 +/- 8.0 nmol/l, and at 12 months was 71.5 +/- 32.5 nmol/l (P = 0.00 vs.
      baseline). After 3, 6 and 12 months iPTH levels were 141.7 +/- 108.4 ng/l (P =
      0.00 vs. baseline), 131.1 +/- 95.7 ng/l (P = 0.03 vs. baseline) and 162.2 +/-
      139.3 ng/l (P = ns vs. baseline). Mean calcium did not change. Mean urinary
      calcium excretion increased significantly (basal: 5.7 +/- 2.9 mmol/24 h, 12
      months: 7.9 +/- 4.9 mmol/24 h, P = 0.02). Cautious calcifediol supplementation
      significantly increased mean 25(OH)D and temporarily reduced mean iPTH. It did
      not change mean serum calcium, but urinary calcium excretion increased
      significantly. We suggest that serum calcium and 24 h calciuria be measured at
      regular intervals in patients with PHTP, while on calcifediol supplementation.

PMID- 19598009
TI  - Gene delivery efficiency in bone marrow-derived dendritic cells: comparison of
      four methods and optimization for lentivirus transduction.
AB  - Many gene delivery methods have been used to transduce or transfect bone marrow
      derived dendritic cells (BMDCs) for genetic engineered DC vaccine research. The
      present study, for the first time, evaluated the efficiencies of four methods
      (lipofection, DNA electroporation, recombinant adeno-associated virus type 2
      (rAAV2) transduction, and recombinant lentivirus (rLV) transduction) using EGFP
      as a report gene in the same BMDC culture system. Our data demonstrate that rLV
      transduction is the most effective method; both lipofection and DNA
      electroporation transfect BMDCs at lower efficiencies; rAAV2 can hardly transduce
      BMDCs. Furthermore, our results, for the first time, demonstrate that rLV
      transduction efficiency on BMDCs can be improved significantly by co
      centrifugation and repeated transduction.

PMID- 19598010
TI  - Down-regulation of miR-31 expression in gastric cancer tissues and its clinical
      significance.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target
      mRNAs. Altered expression of specific miRNAs in several tumor types has been
      reported. However, the expression levels of miR-31 in gastric cancers are
      unclear. The objective of the present study was to compare the expression profile
      of miR-31 between gastric cancer tissues and non-tumor tissues. Real-time
      quantitative reverse transcription-polymerase chain reaction technology was used
      to detect the levels of miR-31 expression. The expression levels of miR-31 in
      gastric cancer tissues were significantly lower than those in non-tumor tissues.
      This new information may help to clarify the molecular mechanisms involved in
      gastric carcinogenesis and to indicate that miR-31 may be a novel diagnostic
      biomarker of gastric cancer.

PMID- 19598013
TI  - [Prognostic analysis of 669 liver metastasis of colorectal cancer cases].
AB  - OBJECTIVE: To evaluate the relation between different therapy and survival rate
      of liver metastasis of colorectal cancer (LMCC). METHODS: Clinical data of 669
      LMCC patients,collected from Fudan University Zhongshan Hospital from January
      2000 to July 2008, were analyzed retrospectively. RESULTS: Of the 669 cases, 379
      cases were synchronous liver metastases(SLM) and 290 cases were metachronous
      liver metastases(MLM). There were no significant differences in age, gender and
      position of primary tumor between SLM and MLM groups(P>0.05), but as to liver
      metastasis characteristics(liver lobe involved, focus number and maximal focus
      diameter) and CEA, CA19-9 before therapy,there were significant
      differences(P<0.05). Two hundred and fifty-three cases underwent curative hepatic
      resection, including 123 cases in SLM and 130 cases in MLM. Until October 31,
      2008, all the cases were followed up. The median survival time of SLM was(11+/-1)
      months and of MLM(23+/-2) months(P<0.01). Five-year survival rate of SLM was 6.4%
      and of MLM 11.4%(P<0.01). As to different treatments, median survival time and 5
      year survival rate of curative hepatic resection group were 37 months and 35.6%,
      and of non-operation groups(i.e. intervention, chemotherapy, radiofrequency
      therapy and percutaneous ethanol injection) were 5 to 26 months and 0 to 3.6%
      respectively(P<0.05). CONCLUSIONS: Curative hepatic resection is the first choice
      of liver metastasis of colorectal cancer, which can improve the survival rate.
      Resection rate and survival of MLM are better than those of SLM.

PMID- 19598014
TI  - [Impact of width of hepatectomy margin on survival after simultaneous liver and
      colorectal resection for colorectal cancer liver metastasis].
AB  - OBJECTIVE: To elucidate an adequate hepatectomy margin for simultaneous liver and
      colorectal resection in colorectal cancer liver metastasis. METHODS: Clinical
      data of 39 patients, undergone simultaneous liver and colorectal resection for
      colorectal cancer liver metastasis from August 1994 to December 2004, were
      analyzed retrospectively. Two groups were divided according to the width of
      hepatectomy margin:less than 1 cm in group A, and equal or more than 1 cm in
      group B. The data were analyzed and compared between the 2 groups using Kaplan
      Meier survival analysis and Log-rank test. RESULTS: There were 14 patients in
      group A and 25 patients in group B. No significant differences in gender, age,
      primary tumor invasion, lymph node metastasis, the number, distribution and size
      of liver metastasis, duration and blood lose of surgery were found between two
      groups. The median survival time was 17 months in group A, and 37 months in group
      B, and the overall 5-year survival rate in group B was much better than that in
      group A (19.8% vs 0, P<0.01). CONCLUSION: Simultaneous liver and colorectal
      resection in colorectal cancer liver metastasis should be performed with a
      hepatectomy margin equal or more than 1 cm.

PMID- 19598012
TI  - Intimate partner homicide.
AB  - Intimate partner homicides represent the most severe outcome of intimate partner
      violence, and constitute more than a quarter (26%) of all homicides in adults
      over 15 years of age in Southern Denmark. In our experience the victims of
      partner homicides are primarily women, often from socially disadvantaged
      families, and that these homicides usually are the result of an impulsive act,
      with the perpetrator often committing suicide after the act. The aim of this
      study was to investigate these hypotheses further, and to provide an up-to-date
      overview of intimate partner homicides in Southern Denmark.

PMID- 19598011
TI  - Physiological effects of the TASER C2 conducted energy weapon.
AB  - In previous studies, exposure to conducted energy weapons (CEWs) (such as TASER
      International's Advanced TASER X26 device) resulted in leg muscle contraction,
      acidosis, increased blood electrolytes, and other biochemical and physiological
      changes. In the current study, experiments were performed to examine the effects
      of exposures to TASER International's "C2" CEW, which is specifically marketed to
      civilian rather than law-enforcement users. Ten pigs (Sus scrofa) were sedated
      with an intramuscular injection of Telezol (tiletamine HCl and zolazepam HCl) and
      intubated. General anesthesia was maintained with an IV propofol infusion.
      Applications of the C2 device for 30 s resulted in extensive muscle contraction
      and significant increases in heart rate and hematocrit, and in blood levels of
      pCO2, lactate, glucose, and potassium, sodium, and calcium ions. Significant
      decreases were observed in blood oxygen saturation, pO2, and pH. Qualitatively,
      many of these changes were consistent with previous reports in the literature
      dealing with studies of muscle stimulation or exercise. The changes in blood
      pCO2, pO2, electrolytes, lactate, and pH, however, were greater than in a
      previous study of three repeated 5-s exposures to the X26 CEW commonly used by
      law-enforcement personnel. On the basis of the results, potential detrimental
      effects due to use of the "citizen-version" TASER C2 CEW may be more likely than
      limited intermittent applications of the X26 CEW.

PMID- 19598015
TI  - [Association between expressions of HSP70, HSP90 and efficacy of chemotherapy in
      colorectal cancer patients with unresectable liver metastasis].
AB  - OBJECTIVE: To investigate the association between expressions of HSP70, HSP90 and
      efficacy of chemotherapy in colorectal cancer patients with unresectable liver
      metastasis. METHODS: Data of 52 colorectal cancer cases, whose primary colorectal
      focuses were resected but hepatic metastatic tumors were unresectable, were
      reviewed retrospectively. All the patients underwent FOLFOX4 regimen well.
      Immunohistochemistry assay was applied to determine the expressions of HSP70 and
      HSP90 in primary focus tissues. The number and size of hepatic metastatic tumors
      pre- and post-chemotherapy were compared by CT scanning. RESULTS: Partial
      remission(PR) rate was 33.3% in cases with up-regulated expression of HSP70,
      while 64.5% in cases with down-regulated expression of HSP70, whose difference
      was significant. PR rate was 50% in cases with up-regulated expression of HSP90,
      and 53.1% in the others with down-regulated expression of HSP90, whose difference
      was not significant. CONCLUSIONS: FOLFOX4 regimen has advantages in cases with
      lower HSP70 expression over those with higher HSP70 expression. HSP90 expression
      level is not associated with the efficacy of FOLFOX4 regimen.

PMID- 19598016
TI  - [Characteristics of lymph node metastasis and prognostic analysis in 157 early
      gastric cancer patients].
AB  - OBJECTIVE: To explore the pattern of lymph node metastasis and its influence on
      the prognosis of early gastric cancer(EGC). METHODS: The pattern of lymph node
      metastasis and the 3-,5-year survival rates in 157 EGC patients undergone surgery
      from October 1995 to October 2005 were analyzed retrospectively. The SPSS 11.5
      statistics software was used to perform univariate and multivariate analysis.
      RESULTS: Twenty-two cases had lymph node metastasis among 157 EGC patients(14%).
      Two mucous cancers(2.4%) and 20 submucosal tumors(27.0%) had lymph node
      metastases (P<0.01). Lymph node metastasis was not seen in minute gastric
      cancer(diameter < or =0.5 cm). Lymph node metastasis rates were 6.4% in the
      cancers with diameter 1.1-2.0 cm and 21.5% in the cancers with the diameter >2.0
      cm(P<0.01). Besides, lymph node metastasis rate of well-differentiated EGC was 0,
      of moderate differentiated EGC 11.1%, and poor-differentiated EGC 0.9%(P<0.01).
      Of 9 cases with vascular cancer embolus, 4 had lymph node metastases. Logistic
      regression analysis showed that tumor size, vascular cancer embolus,
      histopathological type and depth of invasion were independent factors of lymph
      node metastasis in EGC. The 3- and 5-year survival rates of EGC patients with
      lymph node metastasis were 81.6 % and 79.5% respectively, which were much lower
      than those without lymph node metastasis(95.7% and 93.2%, P<0.01). CONCLUSIONS:
      Lymph node metastasis in EGC is mainly correlated with depth of infiltration,
      tumor size, vascular cancer embolus and differentiation. For EGC treatment,
      choice should be made reasonably based on the risk of lymph node metastasis.

PMID- 19598017
TI  - [Pathologic characteristics of residual carcinoma at incisal edge after
      gastrectomy for gastric cancer].
AB  - OBJECTIVE: To explore the reason, features and preventive measures of residual
      carcinoma at incisal edge after gastric cancer operation. METHODS: Clinical data
      of 108 cases with positive incisal margin(6.47%) from December 1964 to December
      2004 in Cancer Center of Sun Yat-sen were summarized and analyzed
      retrospectively. RESULTS: Positive incisal margin patients accounted for
      6.5%(108/1670) of total gastric carcinoma cases during above period. There were
      62 men and 46 women with median age of 54 years(ranged from 23 to 82). The
      residual carcinoma rates of incisal edge were 3.6%(48/1333) in radical resection
      group and 17.8%(60/337) in palliative resection group respectively(P=0.000).
      Also, the residual carcinoma rates were 2.3%(3/129) in early group, 6.8(105/1541)
      in advanced group(P=0.046), 4.5%(37/815) in distal gastrectomy group and
      8.0%(55/689) in proximal group respectively(P=0.000). Residual carcinomas were
      related with pTNM stage, Borrmann type, tumor size, differentiation and invasion
      depth(P<0.05). CONCLUSIONS: Superior gastric carcinoma, Borrmann III(, IIII( type
      advanced cancer, tumor diameter > or =5 cm, poor differentiation or
      undifferentiated type and serosa invaded easily result in residual carcinoma at
      incisal edge. The radical preventive measure is to ensure that incisal edge ought
      to exceed 5 cm apart from the tumor.

PMID- 19598018
TI  - [Effect of laparoscopic-assisted resection of rectal carcinoma on C-reactive
      protein and humoral immunity].
AB  - OBJECTIVE: To investigate the effect of laparoscopic-assisted resection of rectal
      carcinoma on perioperative levels of C-reactive protein (CRP),
      immunoglobulins(Ig) and complements. METHODS: Fifty-four patients with rectal
      carcinoma were divided into laparoscopic group (n=26) and open operation
      group(n=28) according to the patients' will. C-reactive protein (CRP), IgG, IgA,
      IgM, C(3), C(4) and CH(50) of peripheral blood were assayed preoperatively and on
      the 1st, 2nd, 3rd and 7th day postoperatively. RESULTS: Compared with the
      preoperative period, the CRP levels in both groups were significantly increased
      on the 1st, 2nd, and 3rd day(P<0.01) and peaked on the 2nd day postoperatively.
      The postoperative CRP levels were significantly lower in the laparoscopic group
      than those in the open operation group(P<0.01). After operation, the
      immunoglobulin levels were significantly decreased in both groups(P<0.01), and
      there were no significant differences in IgG and IgM. The levels of C(3), C(4)
      and CH(50) were significantly decreased after operation in both groups(P<0.05)
      and returned to the preoperative levels during postoperative 48-72 hours in
      laparoscopic group. CONCLUSION: Laparoscopic-assisted resection of rectal
      carcinoma results in less wound, lower levels of stress response, and less effect
      on immune function compared to open surgery, which recovers the immune function
      of patients more rapidly after operation.

PMID- 19598019
TI  - [Effect of different position and CO(2) pneumoperitoneum on deep vein
      hemodynamics of lower limb].
AB  - OBJECTIVE: To study the effect of laparoscopic surgery position and CO(2)
      pneumoperitoneum on deep vein hemodynamics of lower limb. METHODS: Color Doppler
      ultrasound was adopted to evaluate the diameter, blood velocity and the amount of
      the blood flow in the lower extremity of 37 gastric cancer patients undergone
      laparoscopic surgery from November 2007 to August 2008 in our hospital. Three
      kinds of position(prostration, head-down tilt position and feet-down tilt
      position) before the establishment of pneumoperitoneum and three different
      pressure of CO(2) pneumoperitoneum( 8 mm Hg, 12 mm Hg, 16 mm Hg ) after the
      establishment of pneumoperitoneum were applied during laparoscopic surgery.
      RESULTS: Compared with the stage of prostration before the pneumoperitoneum, the
      femoral vein diameter decreased (P<0.05), the velocity and the amount of blood
      flow increased (P<0.01, P<0.05) in head-down tilt position; the femoral vein
      diameter increased(P<0.01), the velocity and the amount of blood flow
      decreased(P<0.01, P<0.05) in feet-down tilt position or the establishment of
      pneumoperitoneum. Furthermore, with the increase of pneumoperitoneum pressure,
      the femoral vein diameter increased, the velocity and the amount of blood flow
      decreased(P<0.05). CONCLUSIONS: The head-down tilt position is conducive for the
      blood to recirculate, which will degrade the risk of deep vein thrombosis after
      the laparoscopy. The feet-down tilt position and CO(2) pneumoperitoneum can
      interfere the recirculation of blood, and increase the risk of deep vein
      thrombosis after the laparoscopy.

PMID- 19598021
TI  - [Clinical efficacy comparison between laparoscopy and open radical resection for
      191 advanced colorectal cancer patients].
AB  - OBJECTIVE: To evaluate the feasibility, the radicalness and efficacy of
      laparoscopy for advanced colorectal cancer. METHODS: From June 2006 to December
      2007, laparoscopic surgery and open radical resection were performed in 191 cases
      of colorectal cancer. The curative effect and clinical data were collected and
      analyzed. RESULTS: The patients were randomized to two groups, 98 patients
      underwent laparoscopic surgery and 93 open operation. Five cases(5.1%) were
      converted to open surgery in laparoscopic surgery group. The average
      intraoperative blood loss of open surgery group was(279.5+/-189.4) ml, while that
      of laparoscopic surgery group was(87.2+/-27.1) ml, the difference between the two
      groups was statistically significant(P=0.011). Within postoperative 48 hours, the
      intestinal function and early mobile physical activity were restored in 37.8%
      (37/98) and 30.6% (30/98) patients of laparoscopic surgery group, while in
      6.5%(6/93, P=0.000) and 3.2% (3/93, P=0.000) patients of open surgery group, the
      differences between two groups were statistically significant. The average
      hospital stay of laparoscopic surgery group was (8.9+/-5.9) d, whereas open
      surgery group(12.1+/-7.6) d, the difference was statistically
      significant(P=0.036). No significant differences were found between the two
      groups in gender, age, tumor location, resection range of surgery, TNM staging,
      post-operative complication and lymph node harvest(P>0.05). CONCLUSIONS:
      Laparoscopic surgery is feasible for the patients with advanced colorectal
      cancer. The radicalness of laparoscopic surgery is similar to that of open
      surgery, and laparoscopic surgery can provide less intraoperative blood loss,
      better intestinal function restoration, early mobile physical activity and
      shorter hospital stay.

PMID- 19598020
TI  - [Efficacy evaluation of intersphincteric resection during anus-preserving
      operation for ultralow rectal carcinoma].
AB  - OBJECTIVE: To evaluate anorectal dynamics, function and efficacy of ultralow
      rectal carcinoma patients undergone intersphincteric resection(ISR). METHODS:
      From January 2004 to August 2007, 30 patients with ultralow rectal carcinoma(2.5
      4.0 cm distance from anal edge) underwent ISR. All the patients received
      anorectal manometry before and after operation. The postoperative anal function
      was evaluated by Williams continence standard and the treatment outcome was
      followed up. RESULTS: After ISR operation, anal resting pressure, maximum squeeze
      pressure and maximum tolerance volume of the rectum decreased significantly (all
      P<0.01) and restored gradually, but not to normal. The rectal anal inhibitory
      reflex disappeared in 27 patients(90.0%) and was not improved. According to
      Williams continence standard, 86.7%, 93.3% and 96.7% of patients obtained
      acceptable anal function in 3, 6, and 12 months after operation respectively.
      During follow-up of 12 to 44 months, all the patients were still alive and no
      patient developed pelvis or local recurrence, distant metastasis and anastomotic
      leakage. Fecal eczema of anus occurred in 10 patients, colonic mucosa prolapse in
      2 patients and stenosis of anal canal in one patient. CONCLUSION: ISR for
      ultralow rectal carcinoma can not only attain radical treatment outcome, but also
      preserve anal sphincter.

PMID- 19598022
TI  - [Study on radiation sensitivity of colorectal cancer cells using gene expression
      profile].
AB  - OBJECTIVE: To screen the radiosensitivity-related genes of colorectal cancer
      cells. METHODS: Gene expression profiles of two different radiosensitivity
      cells(colorectal cancer cell line Lovo and SW480) were obtained by cDNA array and
      the differences of gene expression profiles between the two cells were analyzed.
      RESULTS: Genes of more than 2-fold expressive differentiation were screened. In
      Lovo cells, 908 up-regulated genes were found, including higher expression genes
      CEACAM5, THBS1, SERPINE2, ARL7, HPGD, while 1312 genes were down-regulated. In
      SW480 cells, higher expression genes were SCD, NQ01, LYZ, KRT20 and ATP1B1.
      CONCLUSION: Gene profiles can reflect the radiosensitivity of colorectal cancer
      cells, which will provide the choice for the further study of radiosensitivity in
      colorectal cancer.

PMID- 19598023
TI  - [Clinical research of bevacizumab in combination with irinotecan, fluorouracil
      and leucovorin for advanced metastatic colorectal cancer].
AB  - OBJECTIVE: To evaluate the efficacy of bevacizumab in combination of
      irinotecan,fluorouracil and leucovorin for metastatic colorectal cancer treated
      by failed prior oxaliplatin -based regiment. METHODS: Sixty-two patients were
      randomly divided into two groups, group A of 30 patients received bevacizumab
      plus irinotecan, fluorouracil and leucovorin, group B of 32 patients received
      irinotecan, fluorouracil and leucovorin. The response rate,change of tumor
      markers,one year survival rate and safety were observed. RESULTS: Tumor response
      rate was 30% in group A, 21.8% in group B respectively. Disease control
      rate(CR+PR+SD) was 80% in group A, 50% in group B. The obvious change of
      concentration of tumor markers was observed between pre-treatment and post
      treatment, which was significantly different in group A(P<0.05). One year
      survival rate, median of time to progression and median duration of survival
      between group A and group B were 26.7% vs 18.8%, 5.9 months vs 3.9 months, 10.9
      months vs 8.9 months(P<0.05). The adverse effect in group A was the same as group
      B. Bevacizumab was associated with hypertension and bradycardia. CONCLUSIONS: The
      chemotherapy of bevacizumab combined with irinotecan, fluorouracil and leucovorin
      results in better efficacy in patients with progressive metastatic colorectal
      cancer.

PMID- 19598024
TI  - [Clinical study of gastrointestinal stromal tumors].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics, surgical
      treatment and prognosis of gastrointestinal stromal tumors(GIST). METHODS: The
      clinicopathological data of 84 patients with GIST undergone resection between
      April 1997 and June 2008 were analyzed retrospectively, and the prognosis was
      evaluated. RESULTS: Out of 84 cases, 42 tumors located in stomach, 24 in small
      intestine, 18 in other sites. Tumor sizes ranged from 0.5 to 25 cm(average 5.6
      cm). Positive rate of CD117 expression determined by immunohistochemical methods
      was 96.4%. Seventy-nine cases underwent complete tumor resection, while 5 cases
      received palliative resection or biopsy. Seventy-eight patients were followed up
      and their 1-, 3-, 5-year survival rates were 92.0%, 79.2%, 72.0% respectively.
      The Fletcher's classification of malignancy risk groups for GIST was related to
      the survival rates(P=0.001). The differences of survival rate among very low risk
      group, low risk group and high-risk group were significant(P=0.003, P=0.000).
      CONCLUSIONS: Complete tumor resection in the initial operation of GIST should be
      emphasized. The Fletcher's classification of malignancy risk groups for GIST is
      related to the survival rate. Extended surgical resection is required for GIST of
      higher malignancy risk.

PMID- 19598025
TI  - [Comparison of long-term efficacy on severe hemorrhoids between procedure for
      prolapse and hemorrhoids and Milligan-Morgan hemorrhoidectomy].
AB  - OBJECTIVE: To compare the long-term results of procedure for prolapse and
      hemorrhoids(PPH) and Milligan-Morgan(MM) hemorrhoidectomy in the treatment of
      third- and fourth-degree hemorrhoids. METHODS: Ninety-one patients in PPH group
      and 120 patients in MM group, treated in our hospital from May 2001 to May 2005,
      were followed up. All the patients suffered with third- or fourth-degree
      hemorrhoids. The data including symptoms relief, complication and recurrence were
      compared between two groups. RESULTS: PPH and MM both significantly relieved
      bleeding (95.6% vs 92.7%), pain (93.1% vs 94.3%) and prolapse (93.4% vs 93.1%).
      There were no significant differences between two groups(P >0.05). PPH
      significantly relieved constipation compared with MM(60.0% vs 32.1%, P <0.05). No
      significant differences of complete relief rates between PPH group and MM group
      according to different degrees, types and prolapses of hemorrhoids were found(P
      >0.05). There were no significant differences in the overall complication
      rate(14.3% vs 12.7%), recurrence rates(12.1% vs 8.8%) and satisfactory degree
      (85.1 vs 88.2) between two groups as well. CONCLUSION: The long-term outcomes of
      PPH in the treatment of third and fourth-degree hemorrhoids are similar to
      Milligan-Morgan hemorrhoidectomy.

PMID- 19598026
TI  - [Study on specific metabonomic profiling of serum from colorectal cancer patients
      by gas chromatography-mass spectrometry].
AB  - OBJECTIVE: To study the specific metabonomic profiling of serum from colorectal
      cancer patients to find out the low molecule metabolites associated intimately
      with colorectal cancer,and to establish specific metabolic model for the
      diagnosis of colorectal cancer. METHODS: The metabonomic profiles of the serum
      samples from colorectal cancer(CRC) patients(n =31) and healthy adults(n =8) were
      investigated by gas chromatography-mass spectrometry (GC-MS) technique combined
      with a commercial mass spectral library for the peak clustering based on
      metabolites. RESULTS: Thirty-four endogenous metabolites including some amino
      acids, carbohydrates, fatty acids and other intermediate metabolites were
      identified. By t test statistics with P<0.05, P<0.01 respectively, L-valine, L
      threonine, 1-deoxyglucose, glycine and ribitol levels were decreased
      significantly, but 3-hydroxybutyric acid level was increased significantly in the
      CRC patient group as compared with healthy adult group. PLS-DA based on these
      metabolites discriminated two groups for each other. Hierarchical clustering
      based on above 6 significant differential metabolites revealed that the
      prediction accuracy of colorectal cancer group was 93.5%. CONCLUSION: GC-MS
      technique is an alternative tool for the metabonomic study and would be certainly
      beneficial to the pathological research, early diagnosis and therapy evaluation
      of CRC.

PMID- 19598027
TI  - [Expression of AIF and caspase-3 in colorectal carcinoma, adenoma, and normal
      mucosa and its correlation].
AB  - OBJECTIVE: To investigate the expression differences of apoptosis-inducing factor
      (AIF) and caspase-3 among colorectal carcinoma, adenoma and normal mucosa, and to
      identify the relationship between AIF and caspase-3 expression in colorectal
      adenoma-carcinoma sequence. METHODS: Formalin-fixed paraffin embedded colorectal
      tissues from 174 cases, including 84 adenomas, 72 carcinomas, and 18 normal
      mucosa, were examined for expression of AIF and caspase-3 by streptavidin
      peroxidase (SP) immunohistochemistry. RESULTS: The positive rates of AIF and
      caspase-3 in colorectal adenoma were higher than those in normal mucosa (P
      <0.05). The positive rate of AIF in adenoma showed no significant difference
      compared to colorectal carcinoma (P >0.05). However, caspase-3 expression in
      adenomas was significantly higher than that in carcinoma (P <0.05). The positive
      rate of AIF in tubular adenoma was significantly higher than that in villous
      adenoma (P <0.05), while the positive expression rate of caspase-3 in the two
      types of adenoma showed no significant difference (P >0.05). AIF expression had
      no prominent correlation with the caspase-3 expression (P >0.05). CONCLUSIONS:
      The dysregulation of caspase-independent pathway of apoptosis may be an early
      event in the development of colorectal carcinogenesis, while the dysregulation of
      the caspase-dependent pathway of apoptosis may be one of contributing factors of
      colorectal carcinogenesis. The caspase-independent pathway of apoptosis and the
      caspase-dependent pathway of apoptosis are two relatively independent pathways in
      colorectal carcinogenesis.

PMID- 19598028
TI  - [Relationship between the protein expression of P53, c-erbB-2, vascular
      endothelial growth factor and CD44 and the survival rates of stage II( colorectal
      cancer patients without radiochemotherapy after radical resection].
AB  - OBJECTIVE: To investigate the relation between protein expression of 4 genes
      [P53,c-erbB-2,vascular endothelial factors(VEGF) and CD44]and survival rate in
      stage II( colorectal cancer(CRC) patients without radiochemotherapy after radical
      resection. METHODS: One hundred and fifty-nine cases of stage II(CRC without
      radiochemotherapy were enrolled in this study. The clinicopathological date and 5
      year follow-up data were reviewed. Streptavidin-peroxidase immunohistochemical
      technique was used to detect the expression of P53, c-erbB-2, VEGF and CD44 in
      formalin-fixed, paraffin embedded sections of CRC tissues from above 159
      patients. RESULTS: The 5-year survival rate was 82.4%. The rates of positive
      expression of P53, c-erbB-2, VEGF and CD44 were 58.5%(93/159), 26.4%(42/159),
      57.9%(92/159) and 40.0%(54/159) respectively. The 5-year survival rates of
      positive expression patients were not significantly different with those of
      negative expression. chi(2) analysis showed that the positive expressions of 4
      genes had no relationships with the prognosis. CONCLUSION: The expression of 4
      gene proteins has no relationship with the prognosis of stage II( CRC patients
      without radiochemotherapy after radical resection.

PMID- 19598029
TI  - [Apoptosis induction effect of siRNA recombinant expression vector targeting
      Livin and Survivin gene simultaneously on human colon cancer cells].
AB  - OBJECTIVE: To investigate the effect of siRNA targeting Livin and Survivin gene
      simultaneously on the proliferation and apoptosis of human colon cancer cells.
      METHODS: SiRNA recombinant expression vectors targeting Livin and Survivin gene
      simultaneously were constructed and transfected into human colon cancer cell line
      Lovo. The effects of siRNA recombinant expression vector on Lovo cells were
      detected by RT-PCR, Western blot, MTT reduction assay and flow cytometry.
      RESULTS: It was confirmed by restriction endonuclease and sequence analysis that
      siRNA recombinant expression vector targeting Livin and Survivin gene
      simultaneously was constructed successfully. The suppressive rates of siRNA
      targeting Livin and Survivin gene simultaneously on Livin mRNA and protein
      expression were 27.9% and 22.3% respectively, and those on Survivin mRNA and
      protein expression were 32.2% and 40.9% respectively. The survival rate of cancer
      cells was decreased whereas the apoptotic rate was increased, but the coordinate
      repression was weaker than Livin and Survivin RNA interference alone.
      CONCLUSIONS: siRNA targeting Livin and Survivin gene simultaneously can decrease
      the expression of Livin and Survivin gene, suppress cell proliferation and induce
      cell apoptosis in human colon cancer. The coordinate repression was weaker than
      Livin and Survivin RNA interference alone.

PMID- 19598030
TI  - [Effect of CD8(+)CD28(-) suppressor T cells induced by dendritic cell with major
      histocompatibility complex 1 expression RNA interference on immune tolerance in
      rat intestinal transplantation].
AB  - OBJECTIVE: To investigate the effect of CD8(+)CD28(-) suppressor T cells(Ts)
      induced by dendritic cell(DC) with major histocompatibility complex 1(MHC-1)
      expression RNA interference on immune tolerance in rat intestinal
      transplantation. METHODS: The expression level of CD8(+)CD28(-)Ts were
      successfully induced by DC with MHC-1 expression interfered by RNA interference
      technique under the stimulator of allograft antigen. Orthotopic intestinal
      transplantation was performed in 36 rats by modified three cuffs method. The
      recipients were randomly divided into three groups(12 rats in each group):group A
      was experimental group with CD8(+)CD28(-) Ts being administrated, mixed T cells
      were injected in group B, while in group C, NS were administrated. On the first
      day and the seventh day posttransplant, the 36 rats of the 3 groups were
      administrated through vena dorsalis penis respectively. Six rats were selected
      randomly from each group and the animals were sacrificed on the 14 th day
      postoperatively, serum levels of TGF-beta, IFN-gamma and the values of Na(+)-K(+)
      ATPase activity of the intestinal graft were assayed and the intestinal
      pathologic morphology, intestinal allograft survival were observed concerning the
      remainders. RESULTS: On the 14 th day after operation, the expression levels of
      TGF-beta and IFN-gamma in group A were significantly up-regulated as compared
      with those in group B and group C(P<0.05). Na(+)-K(+)-ATPase activity in group A
      was(6.3+/-1.0) kU/g, much higher than the levels of group B(3.6+/-0.9)kU/g and
      group C(2.9+/-1.3) kU/g and the differences were significant(P<0.05). The data
      suggested preliminarily that pathological scores of intestinal graft in group A
      were lower than those in group B and group C. The survival time of the recipients
      in group A was 32.0 days, much longer than that in group B (17.5 days, P<0.05)
      and group C(21.0 days, P<0.05). CONCLUSION: CD8(+)CD28(-) Ts induced by DC with
      MHC-1 expression RNA interference can alleviate acute rejection and lead to
      immune tolerance in rat intestinal transplantation.

PMID- 19598031
TI  - [Pathological monitoring of intestinal graft acute rejection in auxiliary en-bloc
      liver-small bowel transplantation].
AB  - OBJECTIVE: To investigate the pathologic monitoring of intestinal graft rejection
      in auxiliary en-bloc liver-small bowel transplantation in pigs. METHODS: Fifty
      outbred long-white pigs were randomized into three groups, and the auxiliary
      composite liver-small bowel allotransplantations were undertaken in 10 pigs in
      group A and group B while segment small bowel allotransplantations were
      undertaken in 10 pigs in group C. Group A and C were not treated with
      immunosuppressive drugs while group B was treated with cyclosporine A and
      methylprednisolone. The postoperative intestinal graft rejections were monitored
      by biopsy through the jejunostomy or ileuostomy on 1, 3, 5, 7, 14, 21 and 30 days
      after operation. Through routine management, the specimens were directly examined
      via optical and electronic microscope respectively. RESULTS: As shown from
      pathological data, the median initial time of postoperative rejection in group A
      was 8 days (ranged from 7 to 12), later than that in group C (5 days:ranged from
      3 to 5), P<0.05). On the 7th day postoperatively, the rejection scores in group A
      was 1.11+/-0.20, lower than that in group C(2.56+/-0.18, P<0.05), but higher than
      that in group B(0.20+/-0.13, P<0.05). Ultrastructure also showed more severe
      intestinal graft rejection in intestinal transplantation than that in combined
      transplantation. The median survival time was 9 days(ranged from 7 to 25) in
      group A and 12 days(ranged from 7 to 20) in group C, while all the pigs in group
      B lived longer than 30 days. CONCLUSION: The pathological assessment through the
      jejunostomy or ileuostomy biopsy is a convenient method to monitor the
      postoperative graft rejections in intestinal related transplantation.

PMID- 19598032
TI  - [Regulation of immune suppressive cytokines by TLR4 activation in colon cancer
      cells].
AB  - OBJECTIVE: To investigate the regulation of Toll-like receptors (TLRs) on immune
      suppressive cytokines in situ colon cancer cells. METHODS: The mRNA and protein
      expression spectrum of TLRs in HT-29 cells were determined by RT-PCR and Western
      blot respectively. The cytokines and chemokines levels of supernant of HT-29
      stimulated by lipoplysaccharide(LPS) were detected with ELISA. RESULTS: TLR1-9
      were expressed in HT-29 cells on mRNA level. After LPS stimulation, TLR4 mRNA and
      protein expressions were up-regulated in HT-29 cells, and TGF-beta, VEGF, IL-8,
      CCL20 and IL-6 levels increased significantly(all P<0.01). Except IL-6, up
      regulation of the other cytokines was not suppressed by NF-kappa B inhibitor.
      CONCLUSION: TLRs expressed on colon cancer cells may elevate the immune
      suppressive cytokines and chemokines, which promote the immune escape of cancer
      cells.

PMID- 19598033
TI  - [Experimental study of human colon cell line Lovo transfected with soluble
      vascular endothelial growth factor receptor 1 gene].
AB  - OBJECTIVE: To investigate the effect of transfection with human soluble vascular
      endothelial growth factor receptor-1(sFlt-1) gene on cell growth and vascular
      endothelial growth factor (VEGF) concentration of the culture supernatant in
      human colon cancer cell line Lovo. METHODS: The recombinant plasmid pcDNA3-sFlt-1
      containing sFlt-1 gene was transfected into Lovo cells by Lipofectamine 2000,
      which was identified by RT-PCR and ELISA. The effect of sFlt-1 protein on cell
      growth and VEGF expression in Lovo cells were investigated by MTT and ELISA.
      RESULTS: The recombinant plasmid pcDNA3-sFlt-1 was successfully transfected into
      Lovo cells. The sFlt-1 expression was identified by RT-PCR and ELISA, which
      inhibited the growth of Lovo cells and reduced the VEGF concentration in the
      culture supernatant compared with control. The inhibitory rates of proliferation
      of Lovo cells via MTT assay after 2,14,21 and 28 days were(23.92+/-9.16)%,
      (13.98+/-10.21)%,(22.54+/-11.92)% and (33.43+/-9.34)% respectively. Compared with
      the control groups, the differences were significant (P<0.05, P<0.01).
      CONCLUSION: Transfection with sFlt-1 gene into Lovo cells results in the
      expression of sFlt-1 protein, which possesses high biological activity and
      inhibits the growth of cancer cells.

PMID- 19598034
TI  - Abstracts of the 2009 Meeting of the Society for Free Radical Research-Europe.
      August 26-29, 2009. Rome, Italy.

PMID- 19598035
TI  - Special symposium on gender-based violence in global health. Introduction.

PMID- 19598036
TI  - Metabolic syndrome and cardiovascular risk factors in the menopausal transition.

PMID- 19598038
TI  - Treatment of scars with flexion contracture using carbon dioxide laser and
      fractional photothermolysis.
AB  - Scars with flexion contracture of various origins are challenging problems which
      may cause not only cosmetic concerns, but also severe functional restriction. In
      this report, we describe a case presenting scars with flexion contracture: a 23
      year-old Korean female with surgical scars on both axillae, which were treated by
      laser-cision (incision using carbon dioxide laser) with second intention wound
      healing followed by a non-ablative fractional photothermolysis system.

PMID- 19598039
TI  - Unmet needs and depressive symptoms among low--income older adults.
AB  - Previous studies have found that declining health, decreased social interaction,
      and inadequate financial resources were significant risk factors for late-life
      depression, and social support from families and friends and religiosity were
      significant protective factors. In this study, we examined if low-income older
      adults' perceived unmet need for home- and community-based services for many
      aging-associated problems would be independently associated with their depressive
      symptoms, controlling for these known risk and protective factors. We interviewed
      a total of 213 community-residing older adults to assess their depressive
      symptoms, using the Geriatric Depression Scale (GDS), and unmet needs in the
      areas of personal assistance, instrumental and environmental support, emotional
      support, and other facilitative/enabling services. We found that the number of
      unmet needs was significantly positively associated with these older adults'
      depressive symptoms, although it explained only a small proportion of the
      variance of the GDS scores. Future research and practice implications are
      discussed.

PMID- 19598040
TI  - Supporting the labor force participation of older adults: an international survey
      of policy options.
AB  - The unprecedented aging of the world's population challenges many institutions,
      including labor markets and public pension programs. This study was conducted to
      survey expert opinions regarding conditions and policies that affect employment
      of older adults. Eighty-nine respondents from 26 nations responded to an Internet
      survey regarding their own experiences with the aging labor force; factors that
      encouraged or discouraged labor force participation of older adults; and
      government responses to these issues. Respondents identified barriers to
      employment of older adults and described their governments' responses. Findings
      illuminate a range of current policy options and suggest possible opportunities
      for innovation.

PMID- 19598041
TI  - Korean american family postcaregivers on dementia caregiving: a phenomenological
      inquiry.
AB  - The purpose of this article is to understand dementia caregiving and
      postcaregiving experience from the Korean-American family caregiver perspective.
      In this transcendental phenomenological study, I analyzed both in-depth
      interviews from 8 caregivers and field notes with the procedure of Moustakas'
      (1994) modification of the Van Kaam method. Five core themes characterized
      participants' experiences: understanding elderly patients with Alzheimer's by
      accepting it as a disease; self-defining and self-appraising of caregivers;
      caregiving as a family affair while examining transgenerational continuity of
      filial piety; returning caregiving to caregivers in turn as a mode of mourning;
      and reviewing dissatisfying experiences with the formal care system. Based on a
      small but relatively heterogeneous sample, this study advances the understanding
      of the underlying, dynamic context of Korean-American family dementia caregiving
      and addresses certain implications of geriatric social work intervention for
      postcaregivers.

PMID- 19598042
TI  - Understanding older men and their male friendships: a comparison of african
      american and white men.
AB  - Friendships can lead to longer and healthier lives. Yet little is known about how
      older men, particularly African American men, define and carry out their
      friendships with other men. This article presents the findings from qualitative
      interviews with 23 African American and 23 White older men who were part of a
      larger study. The subjects were asked whether friendships are important; if they
      have enough male friends; how they define, carry out, and maintain their
      friendships; and the nature of their fathers' friendships. Comparisons are drawn
      between the African American and White men. Implications for social work practice
      are included.

PMID- 19598043
TI  - Unique challenges of transgender aging: implications from the literature.
AB  - Transgender elders are both underserved and understudied. Neither the etiology
      nor prevalence of transgender is well understood. Because sex, gender, and
      sexuality are at the very core of individual identity, it is difficult to
      dislodge one's ideas and feelings about them. Unlike biological sex and sexual
      orientation, gender has several aspects: gender identity, gender expression, and
      gender classification. A discussion of the terminology of transgender is
      presented, and the issues facing aging transgender individuals are identified.
      Although the challenges of adequate healthcare, social support, and legal
      obstacles are faced by many elderly individuals, the way they are presented and
      managed are unique to this often invisible group.

PMID- 19598045
TI  - In/visible bodies: lesbian sexualities and sporting spaces: introduction.

PMID- 19598046
TI  - The qBody project: from lesbians in physical education to queer bodies in/out of
      school.
AB  - The qBody project is a qualitative research study that aims to understand how
      students with "queer bodies" are impacted by heterosexism, transphobia, ableism,
      and fat phobia in Canadian physical education. Approximately 40 adults, who self
      identified as a sexual minority, gender minority, having a physical disability,
      and/or socially undervalued body shape/size were interviewed about how physical
      education impacts their participation in, and alienation from, physical cultures
      later in life. This article situates the theoretical approach of the qBody
      project within the historical development of research into homophobia and
      lesbians in physical education and sport. Specifically, the article traces how
      postmodern theories of embodiment are transforming "lesbian studies in sport"
      into multidimensional studies of marginalization and normalcy-an area that might
      be referred to as "postmodern body studies."

PMID- 19598047
TI  - Girlfight and Bend it Like Beckham: screening women, sport, and sexuality.
AB  - In this article, sport film is taken as a social and cultural space where women's
      bodies are made publicly in/visible. Two films-Girlfight and Bend it Like Beckham
      provide the focus for critical discussion. Moreover, a queer-feminist analysis
      explores the links between participation in boxing and football, and women's
      sexuality as represented in the films. Lesbian sexualities are considered in a
      critique of the erasure of the lesbian sport [film] star. Sexual subjectivity is
      also discussed in relation to the heterosexual heroic and to patriarchy. In this
      way I interrogate heterosexuality. I also consider links between ethnicity,
      women's bodies, and sexuality. In the final instance, I show that the films work
      to reproduce heterosexual hegemony and depict heteronormative assimilation.

PMID- 19598048
TI  - Homonormativity and the politics of race: reading Sheryl Swoopes.
AB  - This article analyzes print media coverage of Sheryl Swoopes' October 2005
      announcement that she is a lesbian. An examination of five key themes that
      emerged in the mainstream, lesbian and gay, and Black press reveals that
      homonormative and White racial discourses were pervasive. Specifically, the
      erasure of Swoopes' racial identity was enabled by narratives about the coming
      out process and the lesbian and gay market. Although there were some disruptions
      to dominant discourses, the coverage overall served to rearticulate Whiteness and
      economic individualism as queer norms.

PMID- 19598049
TI  - "Family-friendly" without the double entendre: a spatial analysis of normative
      game spaces and lesbian fans.
AB  - In this article, I demonstrate the importance of employing a feminist geographic
      framework in order to both read WNBA game spaces and to understand lesbian fan
      participation within these spaces. I argue that attending to the production of
      WNBA game spaces makes visible the ways that normative cultural politics become
      manifest, and brings to the fore the ways that dominant relations are naturalized
      and rarely questioned. Further, attention to the production of these leisure
      spaces compels an examination of the relationship between spatialized normativity
      and claims to, and performances of, lesbian identity. By understanding social
      space as a productive force, it is possible to conduct a critical reading of the
      materiality of WNBA game spaces and the implications for the reproduction of
      naturalized (hetero)normativity. In addition, it illustrates that lesbian fan
      experiences and interpretations of normative WNBA game spaces must be examined in
      a framework that takes seriously the factors that inhibit critical engagement
      with (hetero)normativity, as well as the central role that lesbian fans play in
      the co-production of these spaces.

PMID- 19598050
TI  - Queering lesbian sexualities in collegiate sporting spaces.
AB  - This article utilizes cultural studies praxis, queer theory, and feminist
      poststructuralism to explore the ways in which eight collegiate-level coaches who
      self-identify with non-normative sexualities transgress heteronormative
      boundaries by being "out" or visible in sporting spaces. Data were collected
      through semi-structured qualitative interviews and analyzed within a queer
      feminist hybrid framework (Sykes, 1998). I found that compulsory heterosexuality
      continually worked to silence female coaches with non-normative sexualities
      despite their efforts to change heterosexist sport cultures. Many of these women
      engaged in necessary practical strategies for historically silenced groups
      (Sedgewick, 1990) to create change, such as changing language in athletic
      department policy, and using a politics of difference to challenge the status quo
      on several fronts (e.g., gender, race, ethnicity, sexuality). However, in spite
      of conscientious efforts to do otherwise, poststructuralist and queer
      deconstructions of the transcripts illustrated how forced norms and discursive
      practices inherent in sport regulated both silence and speech for many of the
      interviewees.

PMID- 19598051
TI  - The 2002 Sydney Gay Games: re-presenting "lesbian" identities through sporting
      space.
AB  - In this article poetic representation in qualitative research is explored in
      relation to researching "lesbian" lives. Set within the context of The 2002
      Sydney Gay Games the article considers how poetry can bring to light experiences
      at the intersection of sexuality, sport, and place. The article details three
      aspects to this process. First, by asking what queer theory could do for
      particular research subjects, a robust, malleable, and transportable theoretical
      concept of "queer" is proposed that is responsive to the participants' lives and
      experiences. Second, this concept is applied methodologically in order to
      unsettle more traditional academic modes of representing interview data through
      the use of poetic forms of representation. Finally, a poem constructed from the
      Opening Ceremony of The Gay Games is presented and analyzed. Poetic
      representation is thus offered as a distinct methodology that permits a
      particular kind of "queer" analysis when researching "lesbian" lives.

PMID- 19598052
TI  - Lesbian erotics at women's hockey: fans, flashing, and the Booby Orrs.
AB  - This article analyzes a public breast flashing event that occurred during the
      women's ice hockey tournament at the OutGames/Western Cup Lesbigay athletic event
      in 2007. Employing a postfoundational perspective, I first contextualize the ice
      hockey subculture of the team called the Booby Orrs, outlining some of our
      history, norms, and context. I then tell the particular story that leads to our
      fans flashing their breasts as we finally scored some goals. I end with my
      analysis of this event: how a public nude display of sexualized women's breasts
      in a lesbian-coded public space prompted a resistant sporting moment, at least
      contingently.

PMID- 19598054
TI  - Performance of an N95 filtering facepiece particulate respirator and a surgical
      mask during human breathing: two pathways for particle penetration.
AB  - The protection level offered by filtering facepiece particulate respirators and
      face masks is defined by the percentage of ambient particles penetrating inside
      the protection device. There are two penetration pathways: (1) through the
      faceseal leakage, and the (2) filter medium. This study aimed at differentiating
      the contributions of these two pathways for particles in the size range of 0.03-1
      microm under actual breathing conditions. One N95 filtering facepiece respirator
      and one surgical mask commonly used in health care environments were tested on 25
      subjects (matching the latest National Institute for Occupational Safety and
      Health fit testing panel) as the subjects performed conventional fit test
      exercises. The respirator and the mask were also tested with breathing manikins
      that precisely mimicked the prerecorded breathing patterns of the tested
      subjects. The penetration data obtained in the human subject- and manikin-based
      tests were compared for different particle sizes and breathing patterns. Overall,
      5250 particle size- and exercise-specific penetration values were determined. For
      each value, the faceseal leakage-to-filter ratio was calculated to quantify the
      relative contributions of the two penetration pathways. The number of particles
      penetrating through the faceseal leakage of the tested respirator/mask far
      exceeded the number of those penetrating through the filter medium. For the N95
      respirator, the excess was (on average) by an order of magnitude and
      significantly increased with an increase in particle size (p < 0.001):
      approximately 7-fold greater for 0.04 microm, approximately 10-fold for 0.1
      microm, and approximately 20-fold for 1 microm. For the surgical mask, the
      faceseal leakage-to-filter ratio ranged from 4.8 to 5.8 and was not significantly
      affected by the particle size for the tested submicrometer fraction. Facial/body
      movement had a pronounced effect on the relative contribution of the two
      penetration pathways. Breathing intensity and facial dimensions showed some
      (although limited) influence. Because most of the penetrated particles entered
      through the faceseal, the priority in respirator/mask development should be
      shifted from improving the efficiency of the filter medium to establishing a
      better fit that would eliminate or minimize faceseal leakage.

PMID- 19598055
TI  - Methods for tracking athletes' competitive performance in skeleton.
AB  - In many sports, changes in performance time between races arising from
      differences in venues and weather far exceed changes in an athlete's true
      ability. Here we compare three methods to track performance of individual
      athletes in one such sport, skeleton. We developed the methods with official
      times of 33 male and 34 female athletes competing in three or more of 26 World
      Cup races over 4 years leading up to, but not including, the 2006 Winter
      Olympics. For two methods accessible to coaches, we fitted simple quadratic
      trajectories to each athlete's race placing and to percent behind the winning
      time. For a more sensitive method, we fitted similar quadratic trajectories to
      race time using a mixed model to adjust for mean race times. Correlations between
      predicted and observed performance in the races used to develop the methods were
      all similar ( approximately 0.7). Correlations between predicted and observed
      performance in the Olympics clearly favoured race placing (0.78) over race time
      (0.65) and percent behind the winner (0.63) for women, whereas race placing was
      clearly inferior (0.14) to percent behind the winner (0.30) and race time (0.46)
      for men. All three methods are potentially useful and need further investigation
      in skeleton and other sports.

PMID- 19598056
TI  - Implementing intentions to drink a carbohydrate-electrolyte solution during
      exercise.
AB  - In this study, we examined the effectiveness of a theory-based psychological
      implementation intention strategy on the volume and frequency of intake of a
      carbohydrate-electrolyte solution by participants engaged in submaximal exercise.
      Thirty-five participants were randomly assigned to an implementation intention or
      control condition. Participants assigned to the implementation intention
      condition were required to write down when and where they would carry out their
      intention to drink a sports drink in the upcoming exercise trial. Participants
      completed self-report measures of intentions, the psychological antecedents of
      intentions, and past behaviour for sports drink use and physical activity before
      and after receiving the experimental manipulation. Participants then engaged in a
      one-hour submaximal exercise trial on a cycle ergometer and had free access to a
      carbohydrate-electrolyte solution throughout. The frequency and volume of sports
      drink consumed by participants over the course of the trial was recorded.
      Participants also provided pre- and post-trial urine samples, which were tested
      for osmolality. Experimental participants imbibed a significantly greater volume
      of sports drink and had significantly higher urine osmolality than controls. The
      intervention had no effects on psychological variables. Results support the use
      of implementation intentions to effectively promote sports drink intake among
      sports participants.

PMID- 19598057
TI  - Examining the life story account of the reminiscence bump: why we remember more
      from young adulthood.
AB  - The reminiscence bump is a robust finding demonstrated mostly with the cue-word
      method in Western cultures. The first aim of the study was to replicate the
      reminiscence bump using a life history timeline method and to extend reminiscence
      bump research to a Turkish sample. The second aim was to empirically examine the
      recently proposed life story account (Gluck & Bluck, 2007) for the reminiscence
      bump. The sample consisted of 40 women and 32 men aged 52 to 66 years.
      Participants' lives were divided into 5-year intervals and they verbally reported
      as many memories as possible in a standard timeframe from each interval (in
      random order) and provided ratings of several memory characteristics. As
      expected, the lifespan distribution of the resulting 6373 memories demonstrated a
      reminiscence bump. In support of the life story account, bump memories were found
      to be more novel, more important for identity development, more distinct, and
      more likely to involve developmental transitions than memories from other age
      periods. Findings are discussed in terms of the life story account, which
      synthesises lifespan developmental theory and life story theory.

PMID- 19598058
TI  - The contributions of encoding, retention, and recall to the Hebb effect.
AB  - The article reports an experiment testing whether the Hebb repetition effect-the
      gradual improvement of immediate serial recall when the same list is repeated
      several times-depends on overt recall of the repeated lists. Previous reports
      which suggest that recall is critical confound the recall manipulation with
      retention interval. The present experiment orthogonally varies retention interval
      (0 or 9 s) and whether the list is to be recalled after the retention interval.
      Hebb repetition learning is assessed in a final test phase. A repetition effect
      was obtained in all four experimental conditions; it was larger for recalled than
      non-recalled lists, whereas retention interval had no effect. The results show
      that encoding is sufficient to generate cumulative long-term learning, which is
      strengthened by recall. Rehearsal, if it takes place in the retention interval at
      all, does not have the same effect on long-term learning as overt recall.

PMID- 19598059
TI  - A clinician's perspective of emerging P2Y(12)-directed pharmacotherapies, ex vivo
      measurement tools, and clinical outcomes.
AB  - Platelet-initiated acute thrombosis and coronary embolization are fundamental to
      the pathophysiology of acute coronary syndromes. Pharmacotherapies aimed at
      disrupting platelet function via the P2Y(12) receptor have been successful at
      reducing the incidence of vascular events in randomized clinical trials. However,
      with the emergence of third and fourth generation drugs, several important
      considerations remain, including metabolism, timing of onset, variability in
      platelet response or "resistance", monitoring ability, and off-target effects.
      These fundamental properties and distinct profiles may shape the future of
      cardiovascular therapeutics. Investigation of practical ex vivo platelet
      performance measurement tools is actively proceeding and may provide important
      information for patient management.

PMID- 19598062
TI  - Rare bleeding disorders.

PMID- 19598063
TI  - Introduction. Rare bleeding disorders: general aspects of clinical features,
      diagnosis, and management.
AB  - Rare bleeding disorders (RBDs) are autosomal recessive diseases including the
      inherited deficiencies of coagulation factors such as fibrinogen, factor (F) II,
      FV, FV + FVIII, FVII, FX, FXI, FXIII, and multiple deficiency of vitamin K
      dependent factors, with clinical manifestations ranging from mild to severe. They
      represent 3 to 5% of all the inherited coagulation deficiencies with a prevalence
      in the general population varying between 1 in 500,000 and 1 in 2 million, being
      higher in areas where consanguineous marriages are diffuse. Despite the progress
      made in past years, as a consequence of the rarity of these deficiencies, the
      type and severity of bleeding symptoms, the underlying molecular defects, the
      actual management of bleeding episodes and particularly the prophylactic
      treatment in patients affected with RBDs are not well established. In this
      introductory article, the main features, diagnosis, available treatment options,
      and treatment complications of RBDs will be discussed.

PMID- 19598064
TI  - Congenital fibrinogen disorders.
AB  - Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and
      hypofibrinogenemia) or the quality (dysfibrinogenemia) of the circulating
      fibrinogen or both (hypodysfibrinogenemia). Most often, patients with congenital
      fibrinogen disorders suffer from a bleeding diathesis but paradoxically may
      undergo severe thrombotic episodes. Pregnancy loss is another common clinical
      complication. Even in specialized laboratories, the precise diagnosis of some
      fibrinogen disorders may be challenging. Characterization of the molecular
      defect(s) is important as it provides a more accurate diagnosis, may enable
      prenatal diagnosis, will help elaborate a diagnostic strategy, and may
      distinguish in some cases those patients at risk of thrombosis rather than
      bleeding. However, the phenotype-genotype correlation is not easy to establish,
      and global hemostasis assays may provide a better evaluation of the patient's
      hemostatic state. Replacement therapy is effective in treating bleeding episodes,
      but it is important to tailor individual treatments because the pharmacokinetics
      of fibrinogen after replacement therapy is highly variable among patients.
      Although the number of cases studied and identified mutations are already quite
      substantial, the collection and comparison of molecular, biochemical, and
      clinical data will continue to yield valuable information on the development and
      course of these diseases, as well as on the choice of the most appropriate
      treatments.

PMID- 19598065
TI  - Congenital prothrombin deficiency.
AB  - Prothrombin deficiency is among the rarest inherited coagulation disorders, with
      a prevalence of approximately 1:2,000,000. Two main phenotypes can be
      distinguished: (1) hypoprothrombinemia (type I deficiency), characterized by
      concomitantly low levels of activity and antigen; and (2) dysprothrombinemia
      (type II deficiency), characterized by the normal or near-normal synthesis of a
      dysfunctional protein. In some cases, hypoprothrombinemia associated with
      dysprothrombinemia was also described in compound heterozygous defects. No living
      patient with undetectable plasma prothrombin has been reported to date.
      Prothrombin is encoded by a gene of approximately 21 kb located on chromosome 11
      and containing 14 exons. Forty different mutations have been identified and
      characterized in prothrombin deficiency. Many of them surround the catalytic
      site, whereas another "hot spot" is localized in the recognition domain called
      anion binding exosite I, also called fibrinogen recognition site. Recently,
      mutations were identified also in the Na (+)-binding loop and in the light A
      chain of thrombin. Most hypoprothrombinemia-associated mutations are missense,
      but there are also nonsense mutations leading to stop codons and one single
      nucleotide deletion. Finally, the main aspects of clinical manifestations and
      therapy of congenital prothrombin deficiency are presented and discussed.

PMID- 19598066
TI  - Factor V deficiency.
AB  - Congenital factor V (FV) deficiency is a bleeding disorder associated with mild
      to severe hemorrhagic symptoms and a prevalence in the general population of 1 in
      1,000,000 in the homozygous form. Patients with FV deficiency and clinically
      significant manifestations (mainly involving mucosal tracts) show very low or
      unmeasurable plasma FV levels and are usually homozygous or compound heterozygous
      for mutations located in the FV gene ( F5). Heterozygous carriers have
      approximately half-normal levels of FV and are usually asymptomatic. Replacement
      therapy for FV-deficient patients can only rely on administration of fresh-frozen
      plasma because specific FV concentrates are unavailable and FV is not present in
      cryoprecipitate or prothrombin complex concentrates. A total of 56 mutations have
      been published to date as being responsible for severe or moderately severe FV
      deficiency; more than two thirds of these are null mutations (mainly decreasing
      FV expression), with the remaining being missense mutations (usually impairing FV
      secretion). This article will provide a concise description of the FV protein and
      gene and will review the molecular, clinical, and therapeutic aspects of FV
      deficiency.

PMID- 19598067
TI  - Combined Factor V and Factor VIII Deficiency.
AB  - Combined deficiency of factor V (FV) and factor VIII (FVIII) (F5F8D, or FV+FVIII)
      is a autosomal recessive bleeding disorder caused by mutations in genes encoding
      two components of the endoplasmic reticulum (ER)-Golgi intermediate compartment
      (ERGIC-53), that is, lectin mannose binding protein ( LMAN1) and multiple
      coagulation factor deficiency 2 ( MCFD2), involved in the FV and FVIII
      intracellular transport rather than by DNA defects in the genes that encode the
      corresponding coagulation factors. F5F8D is estimated to be extremely rare
      (1:1,000,000) in the general population, but an increased frequency is observed
      in regions where consanguineous marriages are practiced. F5F8D is characterized
      by concomitantly low levels (usually between 5% and 20%) of both FV and FVIII and
      is associated with a mild to moderate bleeding tendency. Treatment of bleeding
      episodes requires a source of both FV and FVIII; replacement of FV is achieved
      only through use of fresh-frozen plasma (FFP) and replacement of FVIII by FFP and
      desmopressin or specific FVIII concentrates (plasma-derived or recombinant FVIII
      products).

PMID- 19598068
TI  - Factor VII Deficiency.
AB  - The complex formed between the procoagulant serine protease activated factor VII
      (FVII) and the membrane protein tissue factor, exposed on the vascular lumen upon
      injury, triggers the initiation of blood clotting. This review describes the
      clinical picture of FVII deficiency and provides information on diagnosis and
      management of the disease. FVII deficiency, the most common among the rare
      congenital coagulation disorders, is transmitted with autosomal recessive
      inheritance. Clinical phenotypes range from asymptomatic condition, even in
      homozygotes, to severe disease characterized by life-threatening and disabling
      symptoms (central nervous system and gastrointestinal bleeding and hemarthrosis),
      with early age of presentation and the need for prophylaxis. In females,
      menorrhagia is prevalent and affects two thirds of the patients of fertile age.
      Although FVII gene mutations are extremely heterogeneous, several recurrent
      mutations have been reported, a few of them relatively frequent. The study of
      genotype-phenotype relationships indicates that modifier (environmental and/or
      inherited) components modulate expressivity of FVII deficiency, as reflected by
      patients with identical FVII mutations and discordant clinical phenotypes.
      Several treatment options are available for FVII deficiency: the most effective
      are plasma-derived FVII concentrates and recombinant activated FVII (rFVIIa).
      Treatment-related side effects are rare.

PMID- 19598069
TI  - Factor X deficiency.
AB  - Factor X (FX) deficiency is a rare, recessively inherited bleeding disorder
      representing 10% of all rare bleeding diseases and affecting 1 in every 1,000,000
      people. Its clinical presentation places FX deficiency among the most severe of
      the rare coagulation defects, typically including hemarthroses, hematomas, and
      umbilical cord, gastrointestinal, and central nervous system bleeding. Phenotype
      diagnosis is based on the concomitant prolongation of the prothrombin time and
      activated partial thromboplastin time. Through the measurement of plasma level of
      FX antigen and its coagulant activity, two main types of deficiency can be
      distinguished: type I (concomitantly low levels of activity and antigen) and type
      II (low coagulant activity, but normal or borderline antigen levels). FX protein
      is mainly synthesized by the liver and is encoded by a gene ( F10) of 27 kb
      located on chromosome 13, containing 8 exons. One hundred five mutations on F10
      have been identified to date, 78% being missense mutations, with no hot-spot
      regions. There is no specific FX concentrate available, and current treatment
      includes the administration of fresh-frozen plasma or prothrombin complex
      concentrates (PCCs) containing FX in addition to other vitamin K-dependent
      factors. Administration of PCCs is associated with the risk of thromboembolic
      complication due to the unknown concentrations of other coagulant factors;
      however, to overcome this problem, a concentrate containing well-defined amounts
      of FX (and FIX) has recently been developed.

PMID- 19598070
TI  - Factor XI Deficiency.
AB  - Severe factor XI (FXI) deficiency is an injury-related bleeding disorder common
      in Ashkenazi Jews and rare worldwide. In the past two decades, more than 180
      mutations in the FXI gene have been reported in patients with FXI deficiency,
      five of which show a founder effect (Cys38Arg, Gln88Stop, Cys128Stop, Glu117stop,
      and Phe283Leu, the last two largely prevalent among Ashkenazi Jews). Inhibitors
      to FXI after exposure to plasma, FXI concentrates, or Rh immunoglobulin were
      described in patients with mutations resulting in null alleles. Treatment with
      low-dose recombinant activated factor VII in these patients appears promising.
      Survival advantages to patients with severe FXI have been recently reported.
      Herein, we present new observations related to clinic presentation, genotype
      phenotype correlation, and treatment problems in patients with FXI deficiency.

PMID- 19598071
TI  - Factor XIII Deficiency.
AB  - Factor XIII (FXIII) is a tetrameric zymogen (FXIII-A (2)B (2)) that is converted
      into an active transglutaminase (FXIIIa) by thrombin and Ca (2+) in the terminal
      phase of the clotting cascade. By cross-linking fibrin chains and alpha (2)
      plasmin inhibitor to fibrin, FXIIIa mechanically stabilizes fibrin and protects
      it from fibrinolysis. Severe deficiency of the potentially active A subunit
      (FXIII-A) is a rare but severe hemorrhagic diathesis. Delayed umbilical stump
      bleeding is characteristic, and subcutaneous, intramuscular, and intracranial
      bleeding occurs with a relatively high frequency in nonsupplemented patients. In
      addition, impaired wound healing and spontaneous abortion in women are also
      features of FXIII deficiency. The extremely rare B subunit deficiency results in
      milder bleeding symptoms. FXIII concentrate is now available for on-demand
      treatment and primary prophylaxis. A quantitative FXIII activity assay is
      recommended as a screening test for the diagnosis of FXIII deficiency. For
      classification purposes, FXIII-A (2)B (2) antigen in the plasma is first
      determined, and if decreased, further measurement of the individual subunits is
      recommended in the plasma and FXIII-A in platelet lysate. Analytical aspects of
      FXIII activity and antigen assays are discussed in this article. There are no hot
      spot mutations in the F13A1 and F13B genes, and the majority of causative
      mutations are missense/nonsense point mutations.

PMID- 19598072
TI  - Vitamin K-dependent coagulation factors deficiency.
AB  - All vitamin K-dependent coagulation factors require normal function of gamma
      glutamyl carboxylase and vitamin K epoxide reductase enzyme complex (VKORC1).
      Heritable dysfunction of gamma-glutamyl carboxylase or of the VKORC1 complex
      results in the secretion of poorly carboxylated vitamin K-dependent proteins that
      play a role in coagulation. The following review will summarize the clinical
      manifestations of vitamin K-dependent coagulation factors deficiency I and II and
      will provide a detailed explanation about the gene and protein structure, the
      function of the protein, and an analysis of the previously reported mutations.
      Laboratory assays used for diagnosis will be discussed, and treatment for various
      clinical settings will be recommended.

PMID- 19598074
TI  - Whole-body magnetic resonance imaging of healthy volunteers: pilot study results
      from the population-based SHIP study.
AB  - PURPOSE: Approximately 4000 volunteers will undergo whole-body magnetic resonance
      imaging (WB-MRI) within the next 3 years in the population-based Study of Health
      in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the
      feasibility of adding a WB-MRI protocol to a large-scale population-based study,
      (b) to evaluate the reliability of standardized MRI interpretation, and (c) to
      establish an approach for handling pathological findings. MATERIALS AND METHODS:
      The institutional review board approved the study, and oral and written informed
      consent was obtained from each participant. Two hundred healthy volunteers (99
      women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol.
      The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic
      resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography
      in 44 women (44.4%). MR scans were evaluated independently by two readers.
      Abnormalities were discussed by an advisory board and classified according to the
      need for further clinical work-up. RESULTS: One hundred ninety-four (97.0%) WB
      MRI examinations were successfully completed in a mean scan time per subject of
      90 minutes. There were 431 pathological findings in 176 (88%) of the
      participants. Of those 45 (10.4%) required further clinical work-up and 386
      (89.6%) characterized as benign lesions did not. The interobserver agreement for
      the detection of pathological findings was excellent (kappa = 0.799). CONCLUSION:
      The preliminary results presented here indicate that a large prospective,
      population-based study using WB-MRI is feasible and that the results of image
      analysis are reproducible. A variety of positive findings provide valuable
      information regarding disease prevalence in a general adult population.

PMID- 19598075
TI  - Transcripts of calcium/calmodulin-dependent kinases are changed after forskolin-
      or IBMX-induced insulin secretion due to melatonin treatment of rat insulinoma
      beta-cells (INS-1).
AB  - The objective of the present study was to examine the effects of melatonin on
      transcripts of isoforms of calcium/calmodulin-dependent protein kinases in rat
      insulinoma beta-cells INS-1. Investigations show that calcium/calmodulin
      dependent kinase IV and calcium/calmodulin-dependent kinase 2d are expressed in
      human and rat pancreatic islets and INS-1 cells. By application of either
      forskolin or 3-isobutyl-1-methylxanthine for 6 hours, calcium spiking was evoked
      and the release of insulin was increased. The expression of the
      calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d
      transcripts was significantly increased due to forskolin or 3-isobutyl-1
      methylxanthine. Acute melatonin treatment (6 h) in the presence of either
      forskolin or 3-isobutyl-1-methylxanthine caused a significant decrease in insulin
      release and induced significant downregulation of calcium/calmodulin-dependent
      kinase IV and calcium/calmodulin-dependent kinase 2d transcripts in INS-1 batch
      cultures. The attenuating effect of melatonin on transcripts could be almost
      completely reversed by preincubation with the melatonin receptor antagonist
      luzindole. Thus, the insulin-inhibiting effect of melatonin in INS-1 cells is
      associated with significant changes in transcripts of calcium-signaling
      components suggesting that melatonin influences gene expression of components,
      which are known to be involved in insulin secretion or insulin gene expression.

PMID- 19598076
TI  - Effect of L-acetylcarnitine on body composition in HIV-related lipodystrophy.
AB  - This study examined the impact of L-acetylcarnitine treatment on metabolic
      parameters and body composition in patients with lipodystrophy syndrome secondary
      to antiretroviral treatment in human immunodeficiency virus (HIV) infection. A
      total of 9 HIV-1 infected patients with lipodystrophy syndrome (4F/5M, age 41+/-5
      years, HIV duration 8+/-2 years, BMI 23.7+/-3.4 kg/m(2), on protease inhibitors
      and nucleoside analogue Reverse Transcriptase inhibitors) were evaluated before
      and after 8 months of therapy with L-acetylcarnitine (2 g/die) and 9 matched
      healthy subjects served as control subjects. In all patients fasting plasma
      glucose, insulin concentrations (for evaluation of surrogate indexes of insulin
      sensitivity), lipid profile, lipid oxidation (by indirect calorimetry), body
      composition (by DEXA), and intramyocellular triglyceride (IMCL) content of the
      calf muscles (by (1)H NMR spectroscopy) were assessed. After this therapy, in HIV
      1 patients, the IMCL content of the soleus had significantly decreased (p=0.03).
      Plasma FFAs (0.79+/-0.31 to 0.64+/-0.25; p<0.05) and Respiratory Quotient (0.83+/
      0.18 to 0.72+/-0.16; p<0.03) also decreased. Insulin sensitivity was
      significantly lower prior (HOMA-IS 0.56+/-0.30) and nonstatistically different
      than controls after therapy (0.72+/-0.49 vs. 0.78+/-0.42) whilst the percentage
      of fat in the legs increased (p=0.05). Eight months of L-acetylcarnitine
      treatment increased lipid oxidation, decreased intramyocellular triglyceride
      content, and induced a more physiological distribution of fat deposits.

PMID- 19598077
TI  - In vivo knockdown of p85alpha with an antisense oligonucleotide improves insulin
      sensitivity in Lep(ob/ob) and diet-induced obese mice.
AB  - Phosphoinositide 3-kinase is a key signaling intermediate necessary for the
      metabolic actions of insulin. In this study, we assessed the effects of in vivo
      knockdown of the p85alpha subunit of phosphoinositide 3-kinase on insulin
      sensitivity, using an antisense oligonucleotide, in lean mice, diet-induced obese
      mice, and obese leptin-deficient Lep (ob/ob) mice. Mice were injected with either
      p85alpha-targeted antisense oligonucleotide or saline twice weekly for 4 weeks.
      Fasting levels of glycemia and insulinemia and insulin and glucose tolerance
      tests were used to determine insulin sensitivity. Western blot analysis and real
      time polyacrylamide chain reaction were used to assess p85alpha protein and mRNA
      expression. IN VIVO administration of antisense oligonucleotide resulted in 50
      and 60% knockdown of liver p85alpha protein and mRNA, respectively, in the lean,
      diet-induced obese and Lep (ob/ob) mice. This was associated with increased
      phosphoinositide 3-kinase activity and improved insulin sensitivity in diet
      induced obese and Lep (ob/ob) mice. Thus, p85alpha could be an important
      therapeutic target to ameliorate insulin resistance.

PMID- 19598078
TI  - Neuroprotective effect of defatted sesame seeds extract against in vitro and in
      vivo ischemic neuronal damage.
AB  - Sesame (Sesamum indicum L.) is an important oilseed crop that possesses a wide
      spectrum of pharmacological activities. Many studies have been conducted to
      investigate its health-promoting effects. Compared to other plant oils, sesame
      seed oil is highly stable to oxidation and has been demonstrated to have
      protective effects against ischemia-reperfusion injury in the rat brain. However;
      the effects of defatted sesame seeds extract (DSE) have not been studied yet. The
      purpose of this study was to evaluate the protective effect of DSE against
      ischemia models. For in vitro ischemia, oxygen-glucose deprivation followed by
      reoxygenation (OGD-R, 4 h OGD followed by 24 h reoxygenation) in HT22 cells was
      used to investigate the protective effects on cell death and the inhibitory
      effects on lipid peroxidation. For in vivo ischemia, the middle cerebral artery
      occlusion (MCAo, 2 h of MCAo followed by 22 h of reperfusion) rat model was used.
      Twenty-two h after occlusion the rats were assessed for neurobehavioral deficit
      and infarct volume. DSE (0.1-10 microg/mL) significantly reduced the cell death
      and inhibited lipid peroxidation induced by OGD-R. DSE (30, 100 and 300 mg/kg,
      p.o.) given twice at 0 h and 2 h after onset of ischemia reduced brain infarct
      volume dose-dependently and improved sensory-motor function. The therapeutic time
      window of DSE (300 mg/kg, p.o.) was 2 h after MCAo in rats. In conclusion, our
      results show that DSE may be effective in ischemia models by an antioxidative
      mechanism.

PMID- 19598079
TI  - Effects of natural phenolic acids on the skeletal system of ovariectomized rats.
AB  - Recent reports indicate the possibility of antiresorptive and/or bone formation
      increasing activity of natural phenolic acids, commonly present in plants which
      are normally consumed in the diet. The effects of 4 natural phenolic acids
      (ferulic, caffeic, P-coumaric or chlorogenic, 10 mg/kg P. O. daily for 4 weeks)
      on the skeletal system of ovariectomized (estrogen-deficient) rats were
      investigated. Bone mass, mineral and calcium content, macrometric and
      histomorphometric parameters, and mechanical properties were examined. Phenolic
      acids differentially affected the skeletal system of rats with osteoporotic
      changes induced by the ovariectomy. Caffeic acid decreased bone mass, whereas P
      coumaric acid increased the bone mass/body mass ratio and bone mineral mass/body
      mass ratio in the long bones, in comparison with the ovariectomized control rats.
      The phenolic acids improved some bone histomorphometric parameters, impaired by
      estrogen deficiency. However, they did not increase the ratio of bone mineral
      mass to bone mass, decreased by estrogen deficiency, and did not significantly
      affect bone mechanical properties. In conclusion, different natural phenolic
      acids exert differential effects on the skeletal system of ovariectomized rats,
      both favourable and deleterious.

PMID- 19598080
TI  - Effects of magnesium lithospermate B and its analogues on Ca(2+) homeostasis in
      cultured rat thoracic aorta vascular smooth muscle cells.
AB  - Magnesium lithospermate B (MLB), sodium rosmarinate (SR), and magnesium
      lithospermate (ML) are biologically active components isolated from aqueous
      extracts of the Chinese medicine Danshen, the dried root and rhizome of SALVIA
      MILTIORRHIZA Bunge (Labiatae). These compounds share similar chemical structures
      of polyphenols and oligomer condensates with caffeic acid. In this study, we
      compared the effects of MLB, ML, and SR on intracellular Ca (2+) concentrations
      ([Ca (2+)] (i)) in cultured rat thoracic aorta vascular smooth muscle cells
      (VSMCs), using the Ca (2+)-sensitive dye, Fluo-3, as an indicator. In our
      experiments, MLB, ML, and SR did not affect the basal value of [Ca (2+)] (i) in
      VSMCs. In the absence of extracellular Ca (2+), the [Ca (2+)] (i) increase in
      VSMCs induced by 20 microM ATP was attenuated by MLB, ML, and SR in a dose
      dependent manner. Moreover, under this condition, MLB suppressed the increase in
      [Ca (2+)] (i) in VSMCs induced by 1 microM thapsigargin, but not ML or SR. In the
      presence of extracellular Ca (2+), the [Ca (2+)] (i) increase in VSMCs induced by
      60 mM KCl was attenuated by MLB and SR in a dose-dependent manner, but not by ML.
      These results suggest that MLB, ML and SR regulate Ca (2+) homeostasis in VSMCs
      via different pathways. Our findings should aid in elucidating the mechanisms of
      the vasodilator action of aqueous extracts of SALVIA MILTIORRHIZA.

PMID- 19598081
TI  - Two new cytotoxic triterpene glycosides from the sea cucumber Holothuria scabra.
AB  - Two new triterpene glycosides, scabraside A (1) and B (2), and a structurally
      known compound (3), were isolated from the sea cucumber Holothuria scabra
      (Holothuriidae) collected from the South China Sea. Structure of these compounds
      was elucidated by spectroscopic and chemical methods. The glycosides 1 and 2
      exhibit the same common structural features, i. e., the presence of 12- and 17
      hydroxy groups in the holostane-type triterpene aglycone with a 9(11)-ene bond,
      but are different in the side chains of the triterpene aglycone. The glycosides 1
      and 2 had significant in vitro cytotoxicity against four human tumor cell lines
      in comparison to 10-hydroxycamptothecin.

PMID- 19598082
TI  - [50th Congress of the German Society for Pneumology and Respiratory Medicine].

PMID- 19598083
TI  - [Interview -- medical malpractice --medical treatment errors: rehearsed behavior
      ].

PMID- 19598085
TI  - In vitro activity of Arbutus unedo against Leishmania tropica promastigotes.
AB  - Pentavalent antimonials are the first choice for the treatment of anthroponotic
      cutaneous leishmaniasis (ACL) in health centers in Turkey, however in rural
      areas, traditional plants may be preferred for the treatment of lesions. In
      recent years a number of papers are published related to the natural products
      especially plant derivates. Our aim is to investigate the antileishmanial effect
      of Arbutus unedo which is a wild plant mainly grown in maquis and rocky places of
      the seabord in South Europe. In the present study, the ethanolic, water and n
      hexane extracts from the leaves of Arbutus unedo were originally tested in vitro
      against Leishmania tropica promastigotes. The ethanol extract of Arbutus unedo
      leaves at the concentrations of 100, 250, 500 microg/ml were found to be more
      effective than the other extracts (p:0.000). Our study showed that the ethanolic
      extract of Arbutus unedo leaves can be a promising antileishmanial agent and
      further experiments are needed.

PMID- 19598084
TI  - [The serological and entomological survey of zoonotic visceral leishmaniasis in
      Ayvacik Region of Canakkale Province, Turkey].
AB  - The field studies were carried out in Ilyasfaki village belonging to Ayvacik
      town, Kalabakli village and center of Kepez town belonging to Canakkale province
      to determine the epidemiological situation of visceral leishmaniasis between June
      and August 2007. A total of 27 blood samples were taken from the dogs which are
      known as reservoir of Leishmania infantum causing visceral leishmaniasis in human
      and dogs. The dogs were also examined physically for clinical symptoms of the
      disease. A total of 789 sand fly specimens were collected using CDC miniature
      light traps and examined. Six Phlebotomus and one Sergentomyia species were
      identified as: Phlebotomus negletus, P. tobbi, P. simici, P. papatisi, P.
      perfiliewi, P. halepensis and S. theodori. Among these species P. neglectus, was
      found to be a dominant species in Ilyasfaki village by the rate of 94.4%, while
      P. tobbi was also found to be a dominant species in city center (including Kepez)
      and Kalabaki village by the rate of 50% and 48.1%, respectively. No seropositive
      dogs were found by IFA test. Seropositivity below cut-off level was only observed
      in two dogs from Kepez, in dilutions of 1/16 and 1/64. The risk level for human
      and canine visceral is found to be high and it requires more field studies on
      canine leishmaniasis in and around the area.

PMID- 19598086
TI  - Seroprevalence of Neospora caninum and coexistence with Toxoplasma gondii in
      dogs.
AB  - Neospora caninum is a protozoal agent causing abortion and infertility problems
      in dairy cattle. The objective of the present study was to detect the
      seroprevalence of N.caninum in dogs and its co-existence with Toxoplasma gondii
      in some rural and urban regions of Kirikka-le province. A total of 121 blood
      samples were examined with indirect immunoflorescent antibody test to detect the
      presence of N.caninum IgG antibodies. The seropositivity of N.caninum was 28.9%
      in dogs. The seropositivity rate was higher in male dogs than that of females (p
      < 0.05). The seropositivity rate of N.caninum was 36.5% and 20.7% for pure breed
      and mongrel dogs, respectively (p > 0.05). There was no significant difference
      amongst the age groups and location of the dogs (rural or urban) (p > 0.05). The
      N.caninum positive serum samples were also examined for the presence of
      antibodies for T.gondii by Sabin-Feldman Dye test in order to identify the
      possible serological co-infection, 1/16 and higher titres were evaluated as
      positive. According to test results, 19 out of 35 N.caninum seropositive dogs
      (54.3%) showed T.gondii seropositivity.

PMID- 19598087
TI  - [The molecular diagnosis of cryptosporidiosis in fresh and formalin preserved
      fecal samples].
AB  - The acid-fast staining method is widely used in the diagnosis of
      cryptosporidiosis, a disease causing diarrhea in humans. However in this
      technique, some of Cryptosporidium spp oocysts can not be stained and seen as
      formed "ghost-like bodies" and which can only be evaluated by experienced
      microscopists. In the recent years, PCR technique which is proven to be also
      highly sensitive in diagnosis and genotyping, is used as an alternative method.
      In our study we aimed to evaluate the efficacy of PCR in diagnosis of
      cryptosporodiosis. Thirty-three stool samples, belonging to 22 patients who
      applied to Ege University Hospital, Parasitology Clinic between August 2001 -
      August 2003 and microscopically diagnosed as cryptosporodiosis has been included
      in the study. Twenty-three of these 33 samples were processed immediately, while
      ten samples were stored in 10% formalin. As the control group, 11 stool samples
      including 8 specimens with different parasites and 3 negative samples were
      selected. Nested-PCR is applied to all samples. The sensitivity and specifity of
      the method for fresh and formalin preserved samples were found to be 100% and
      50%, respectively. As a conclusion, PCR technique is found to be useful for
      diagnosis in cryptosporodiosis patients with especially those including few
      oocysts in their fresh feces.

PMID- 19598088
TI  - [Determination of the incidence of toxoplasmosis and cystic echinococcosis in
      Kocaeli].
AB  - We determined the incidence of toxoplasmosis and cystic echinococcosis (CE) in
      388 healthy high school students who reside in Kocaeli region and were not
      previously diagnosed as toxoplasmosis and CE positive. The collected serum
      samples were tested with ELISA for the presence of toxoplasmosis and CE.
      Toxoplasmosis serology was positive at 61 people (18%). Among them, 90% had the
      raw meat consumption habit and 81.7% had the history of close contact with cats.
      There was a statistically positive correlation between the raw-meat-consuming
      females and toxoplasmosis seropositivity (p < 0.05). The serology of CE was
      positive in 30 (8.9%) samples. Eighty percent of these, eozinophili was detected
      and a positive correlation was observed with CE (p < 0.05). Also, a positive
      relationship was detected between CE and males who had close contact with dogs (p
      < 0.05). Two students who were serologically positive with high titrations and
      one of them had the ultrasound test. A cyst with a diameter of 4-cm was observed
      in his liver. The results of this study led us conclude that the real incidence
      of the parasitic diseases and the endemic sites should be determined with
      seroepidemiological studies and the citizens, especially students should be
      informed about the contagion ways and precautions.

PMID- 19598089
TI  - [The investigation of malaria cases in Bursa between 2006-2008].
AB  - Malaria caused by Plasmodium parasites is one of the most common infectious
      diseases and an enormous public health problem. In this study, malaria cases
      detected and reported by the Malaria Control Dispensary of the Infectious Disease
      Division of Bursa Health Directory from October 2006 through December 2008 have
      been reported. The cases were evaluated according to age, gender, occupation and
      localization of the cases (indigenous or imported cases). A total of 23.416 blood
      smears were examined during this 26-month period and malaria parasite was found
      in 9 cases (0.038%). Of the 9 positive cases, 8 (88.9%) were male and 1 (11.1%)
      was female. Of these, 4 (44.5%) were acquired in Azarbajcan; 1 (1.1%) in
      Pakistan; 1 (1.1%) in Ghana; 1 (1.1%) in Sudan; 1 (1.1%) in an unknown Africa
      country; and 1 (1.1%) in the southeastern of Turkey. Except for three cases of
      foreign origin infected with Plasmodium falciparum, all the other cases were
      caused by Plasmodium vivax. The 0.05% decrease in malaria cases during the last
      26-month, compared with prior data of malaria prevalence in Bursa, resulted
      primarily from a decrease in the number of cases acquired in Turkey.

PMID- 19598091
TI  - [Antigen detection methods in diagnosis of amebiasis, giardiasis and
      cryptosporidiosis].
AB  - Amebiasis is a significant health problem in developing countries. Humans are
      infected by two morphologically identical species of Entamoeba. Entamoeba
      histolytica causes amebic colitis and liver abscess, and Entamoeba dispar is
      noninvasive. Giardia intestinalis infection is seen worldwide and in all age
      groups. But giardiasis is especially prevalent in countries with poor sanitation
      and unsafe water, where it's responsible for most cases of childhood diarrhea.
      Cryptosporidium parvum, a protozoon, is an obligate intracellular parasite which
      can cause fatal diarrheal disease in immunocompromised individuals. Generally,
      the diagnosis of human intestinal protozoa depends on microscopic detection.
      Microscopic detection is inexpensive, but it is very labor-intensive and requires
      a skilled microscopist. Antigen detection methods (direct fluorescent antibody,
      enzyme immunoassay, and rapid, dipstick-like tests) can be performed quickly and
      do not require an experienced and skilled microscopist. Recently, commercially
      available diagnostic kits for the intestinal parasites E. histolytica,
      G.intestinalis and Cryptosporidium spp. use the laboratory diagnosis. In this
      review, we aimed to discuss the diagnosis of these three intestinal parasites
      using the antigen tests.

PMID- 19598090
TI  - [The role of protozoan parasites in etiology of urticaria].
AB  - In order to investigate a possible link between parasites and chronic urticaria,
      the prevalence of intestinal protozoans in stool samples of individuals with
      chronic urticaria (n=55) and healthy controls (n=43) were evaluated with native
      lugol, formol-ethyl acetate concentration and trichrom dye, modified acid fast.
      In the case of Giardia intestinalis (G. intestinalis) ELISA was also used. In the
      study 29.1% of the patients were found to have protozoan (Blastocystis hominis +
      G.intestinalis) infections. On the other hand, only 11.6% of the patients in
      healthy group were having a protozoon infection, all of which were B. hominis.
      There was no statistically significant difference between the patient group and
      control group regarding the frequency of B. hominis presence. Also, the number of
      G.intestinalis positive patients were also statistically different in patient
      group from those of healthy controls. In patients whom were positive for
      protozoan infections, agent specific therapy was used. In 7 of these patients
      symptoms of the disease were subsided with this therapy while six continued to
      have relapses. Three patients had missed the control visits therefore the course
      of the disease was not evaluated. As a conclusion, protozoans should be
      considered in the etiology of chronic urticaria and stool examination should be
      done in these patients routinely.

PMID- 19598092
TI  - Mesenteric Doppler ultrasonography findings of Echinococcus multilocularis
      infection: an experimental study.
AB  - The diagnosis of alveolar echinococcosis, caused by the larval stage of
      Echinococcus multilocularis, is often difficult and almost always possible only
      in the later stages of the disease. In this study, we aimed to evaluate the
      findings of Doppler ultrasonography images for the diagnosis of intraabdominal
      non-visceral alveolar echinococcosis in Meriones unguiculatus. Six infected
      animals were studied. Abdominal Doppler ultrasonography examinations were
      performed 20-25 days after the implantation. Then, animals were sacrificed and
      infected specimens were histopathologically examined. The sonographic
      examinations of the infected animals revealed lobulated, heterogeneous cystic
      intraabdominal masses. There were echogenic solid areas with hypoechoic and
      anechoic cystic areas within the lesions. Doppler ultrasound examination revealed
      vascular islands within those heterogeneous cystic lesions. Color mode showed
      multiple vascular coding areas within the solid part of the lesions, most of them
      were venous structures but there were also arterial vessels showing dominant flow
      with low resistive indices. Vascular structures were supposed to be the invaded
      native mesenteric vessels within the infiltrating inflammatory mass lesions. We
      consider that the Doppler ultrasound finding of irregular mesenteric vascular
      structures within intraabdominal heterogenous mass lesions may be an important
      sign for the diagnosis of experimental non-visceral alveolar echinococcosis in
      Meriones unguiculatus.

PMID- 19598093
TI  - [The investigation of frequency of cystic echinococcosis in the autopsies
      committed in the Speciality Department of Istanbul Forensic Medicine Institute].
AB  - Cystic echinococcosis, which is caused by a parasite called Echinococcus
      granulosus, is a disease frequently find in the liver and in the lungs. In many
      countries, it is an important public-health problem. This study was done to find
      out the prevalence of Cystic echinococcosis in forensic autopsies performed for
      sudden death cases. This investigation was realized between July 2003-January
      2004 at Istanbul Forensic Medicine Institution. During this six month period,
      total of 1687 autopsies were performed. Of those, 56 autopsy cases had
      macroscopic unknown cysts. The sera obtained from these 56 autopsy cases were
      examined by IgG Enzyme-linked Immunosorbent assay (ELISA) and IgG Indirect
      Hemaglutination (IHA) methods. In the end of the serologic evaluation, of 56
      cases with macroscopic unknown etiology cysts, 34 cases (60.7%) were
      serologically positive for cystic echinococcosis, of those 8 were females (14.2%)
      and 26 were males (46.4%). This study shows that cyst echinococcosis may be find
      frequently in postmortem cases. The fact that the people who perform autopsies
      must work carefully and in hygienic conditions is another important lesson
      obtained from the study.

PMID- 19598094
TI  - What is the importance of Demodex folliculorum in Behcet's disease?
AB  - Demodex folliculorum is an obligate parasite and commonly detected in patients
      with immune system deprivation. This study is planned to document the Demodex
      folliculorum prevalence among patients with Behcet's disease (BD). The patients
      who referred to the ophthalmology clinic were included in the study. Fourty
      patients with BD and 131 patients with refractive errors without any ocular and
      systemic disease were included. For parasite detection, 3 eyelashes from each
      inferior eyelid were epilated. Standardized skin surface biopsy (SSSB) was
      performed for detection of parasite at cheeks of patients. Samples were prepared
      with Hoyer's solution and investigated under the light microscope. There were 15
      female and 25 male in BD group and 61 female and 70 male patients ine control
      group. Mean ages were 37.62 and 38.38 for BD and control groups, respectively.
      Demodex folliculorum prevalence at eyelashes was 65% for BD and 10% for control
      group. SSSB of cheek revealed 7.5% positivity for BD and 10% for control group
      patients. Statistical analysis documented a significant difference for eyelashes
      (p < 0.05) which could not be detected for skin results. Investigation of Demodex
      folliculorum in BD may be useful, even in patients without any complaint, for the
      treatment of ocular and eyelid discomforts of these patients.

PMID- 19598095
TI  - [Determination of parasite fauna of chicken in the Van region].
AB  - The aim of this study was to determine the parasite fauna of the chicken in Van
      Province in 2002 and 2003. The material of the present study included
      endoparasites and ectoparasites determined by rutine parasitological
      examinations. Direct, flotation and sedimentation techniques for endoparasites
      were used. The total of endoparasites and ectoparasites were determined as 85%
      and 76% respectively. The ratios of endoparasites obtained from the chicken were
      coccidial oocystis 65%, Echinostoma spp. 2%, Davania proglottina 8%, Raillietina
      spp. 10%, Trichostrongylus tenuis 4%, Dispharynx nasuta 1%, Ascaridia galli 13%,
      Heterakis gallinarum 15%, Capillaria spp. 30% whereas ratios of ectoparasites
      were Goniocotes hologaster 32%, Lipeurus heteragraphus 6%, Eomenacanthus
      stramineus 42%, Menacanthus cornutus 11%, Menopon gallinae 22%.

PMID- 19598096
TI  - Distribution of Nosema phyllotretae (Microspora, Nosematidae) Weiser, 1961 in
      populations of Phyllotreta atra (Coleoptera, Chrysomelidae) in Turkey.
AB  - The distribution of Nosema phyllotretae infection of Phyllotreta atra populations
      in Turkey is reported for the first time. In total, 48 of the 1668 beetles from
      24 samples collected in five localities were infected by the parasite. Nosema
      infection was found in P. atra adults from only one of the five localities
      studied. The infection average was 2.8% and it reached 42.5% in some samples. The
      results showed that N. phyllotretae infection occurs in P. atra populations in
      restricted localities within Turkey.

PMID- 19598097
TI  - [The occurrence of the hindgut ciliate Blepharocorys curvigula (Ciliophora:
      Blepharocorythidae) from horses (Equus caballus Linnaeus, 1758) in the vicinity
      of Izmir].
AB  - Blepharocorys curvigula Gassovsky, 1919 found in the intestine of domestic horses
      (Equus caballus Linnaeus, 1758), living in the vicinity of Izmir was
      investigated. It was seen in nine of the thirteen horses examined (69%). This
      study reports the presence of Blepharocorys curvigula in the intestine of Equids
      for the first time in Turkey. Specimens were found to be similar to the original
      descriptions on the basis of morphological characters and biometric data.

PMID- 19598098
TI  - [Case report: two Plasmodium vivax malaria cases in the Van Province].
AB  - Malaria is an important parasitic infection which is endemic in the Eastern
      Mediterranean and Southeastern Anatolia regions and sporadic in other regions of
      Turkey, while Plasmodium vivax is the most common cause. Two patients who were
      admitted to our hospital in October with complaints of high fever, chills, nausea
      vomiting, generalized body pain and fatigue and diagnosed as P. Vivax malaria are
      presented, because they were two brothers with no history of travel outside of
      Van city.

PMID- 19598099
TI  - [Case report: primary localization of a hydatid cyst in the adductor brevis
      muscle].
AB  - We present a rare case of primary muscular hydatidosis in the left thigh of a 20
      year-old man, who presented with painless mass. Ultrasound and magnetic resonance
      imaging examinations revealed a multilocular intramuscular cyst in the
      posteromedial compartment of the left thigh mainly occupying the adductor brevis
      muscle. This site of localization has not been reported previously. The patient
      was treated successfully by preoperative and postoperative dual treatment of
      albendazole together with surgery. Hydatid disease should be included in the
      differential diagnosis of muscular masses, regardless of its location, especially
      in endemic areas.

PMID- 19598101
TI  - Case report: mediastinal hydatid cysts.
AB  - Although the intrathoracic location is common for hydatid cyst, chest-wall,
      mediastinal, pericardial, myocardial, fissural and pleural-space locations have
      been reported. The incidence of mediastinal involvement is 0.1-0.5%. Here in this
      paper, two cases of mediastinal hydatid cysts are reported. Both of them had
      anterior mediastinal hydatidosis, while one of the patients had also additional
      three pericardial hydatid cysts. They have undergone thoracotomy for the removal
      of cystic lesions. Hydatid cysts should be considered in the differential
      diagnosis of mediastinal cystic lesions especially in the endemic regions.
      Surgical removal is the treatment of choice for mediastinal hydatid cysts, and
      additional medical therapy may avoid recurrence.

PMID- 19598100
TI  - [Case report: secondary pleural hydatidosis].
AB  - Hydatid cyst has a predilection to locate in liver, lungs, and brain.
      Intrathoracic extrapulmonary locations are generally the mediastinum, pleura,
      pericardium and chest wall. Pleural involvement usually follows the rupture of a
      pulmonary or hepatic cyst inside the pleural space causing secondary pleural
      hydatidosis. Radiological investigations of a patient suffering from cough and
      dyspnea revealed multiple cysts located in the posterior lower right hemithorax,
      and implanted in the diaphragmatic pleura and parietal pleura lining the chest
      wall. He had undergone two hepatic hydatid cystectomy operations. These multiple
      cysts were removed by thoracotomy. The possibility of secondary pleural
      dissemination should be considered in patients with lobulated cystic masses as
      well as a previous hepatic cystic hydatid disease.

PMID- 19598102
TI  - [Case report: hookworm infection in a patient with severe anemia].
AB  - In this study, a patient who was hospitalized with a severe anemia in the
      Internal Medicine Clinic of the Health Research and Application Hospital of
      Yuzuncu Yil University for one week is presented. The patient had fatigue,
      paleness and dizziness for one month and approximately 12 kg weight lost for four
      mounts previous to admission.. Severe iron deficiency anemia was diagnosed in the
      patient by laboratory analyses. Because there were no hematologic factors
      associated with severe anemia, the stool examination was also performed. In the
      Parasitology Laboratory, stool microscopy of the patient revealed numerous ova of
      hookworm. General condition of the patient well improved with anti-parasitic and
      anti-anemia treatment. It was concluded that patients with iron deficiency anemia
      diagnosed in health centers should be also examined for the intestinal parasitic
      diseases encountered rarely, and physicians should consider non-endemic parasitic
      diseases in their provinces.

PMID- 19598103
TI  - [Case report: an intestinal obstruction due to ascariasis].
AB  - Ascaris lumbricoides (A. lumbricoides) with which one billion people around the
      world is infected is also widely seen in Turkey. This case report presents an
      ascariasis infection which displayed typical radiological findings in Kocaeli, a
      non-endemic region of Turkey. The patient was admitted to hospital with symptoms
      of heavy abdominal pain, nausea-vomiting and weakness. The symptoms had started
      weakly three weeks earlier and the patient had applied to a private health care
      center. After a through examination with several appropriate tests including a
      barium small-bowel enema, a morphological finding similar to helminth was
      observed filling the lumen of the jejunum. When rectal swabs were examined A.
      lumbricoides oocytes were discovered. The patient was treated for two days with
      nasogastric drainage, piperazine (3.5 gr/day) in addition to a supportive
      therapy. The patient was surgically diagnosed to have a jejunal obstruction due
      to ascariasis.

PMID- 19598104
TI  - [Ceratothoa oestroides (Risso, 1826) (Isopoda: Cymothoidae) in black seabream
      from the Northern Aegean Sea].
AB  - Ceratothoa oestroides (Risso, 1826), is an ectoparasite found in a variety of
      fish species. This parasite was detected on caudal pedoncule of black seabram
      (Spondyliosoma cantharus) hunted in Balikesir. This is the first report of C.
      oestroides in the black seabram (Spondyliosoma cantharus).

PMID- 19598105
TI  - XRASGRP2 is essential for blood vessel formation during Xenopus development.
AB  - Ras guanyl nucleotide-releasing protein 2 (RASGRP2), one of the Ras guanine
      exchange factors, is implicated as a critical regulator of inside-out integrin
      activation in human lymphocytes, neutrophils and platelets. However, the
      activities of this protein in endothelial cells remain unclear. In the current
      study, we identify a physiological function in blood vessel formation for
      XRASGRP2, which is the Xenopus ortholog of mammalian RASGRP2. XRASGRP2 over
      expression induced ectopic vascular formation, and XRASGRP2-knockdown embryos
      showed delayed vascular development. We also investigated the upstream signaling
      of XRASGRP2 in endothelium formation. XRASGRP2 expression was up-regulated in the
      presence of VEGF-A and down-regulated following VEGF-A depletion. XRASGRP2
      knockdown abolished the ectopic induction of endothelial cells by VEGF-A in the
      posterior ventral blood island. These results suggest that XRASGRP2 is essential
      for vascular formation during Xenopus development.

PMID- 19598106
TI  - Ectophosphodiesterase/nucleotide phosphohydrolase (Enpp) nucleotidases: cloning,
      conservation and developmental restriction.
AB  - Ectonucleotidase proteins occupy a central role in purine signalling regulation
      by sequentially hydrolysing ATP to ADP and to adenosine. The ENPP ( or PDNP) gene
      family, which encodes ectophosphodiesterase/nucleotide phosphohydrolases, is a
      subfamily of these enzymes, which consists of 7 members in mammals. These
      proteins catalyse the generation of bioactive lipids, placing the ENPP enzymes as
      key regulators of major physiological signalling pathways and also important
      players in several pathological conditions. Here we report the cloning of all the
      members, except enpp5, of the enpp family in Xenopus laevis and tropicalis.
      Phylogenetic analyses demonstrate the high level of conservation of these
      proteins between amphibian and other vertebrate species. During development and
      in the adult frog, each gene displays a distinct specific expression pattern,
      suggesting potentially different functions for these proteins during amphibian
      embryogenesis. This is the first complete developmental analysis of gene
      expression of this gene family in vertebrates.

PMID- 19598107
TI  - Increased cellular turnover in response to fluoxetine in neuronal precursors
      derived from human embryonic stem cells.
AB  - Previous reports have shown that antidepressants increase neuronal cell
      proliferation and enhance neuroplasticity both in vivo and in vitro. This study
      investigated the direct effects of one such antidepressant, fluoxetine , on cell
      proliferation and on the production of neurotrophic factors in neuronal
      precursors derived from human embryonic stem cells (hESCs; H9). Fluoxetine
      induced the differentiation of neuronal precursors, strongly enhancing neuronal
      characteristics. The rate of proliferation was higher in fluoxetine -treated
      cells than in control cells, as determined by MTT [3(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide] assay. The CPDL (cumulative population doubling
      level) of the fluoxetine-treated cells was significantly increased in comparison
      to that of control cells (p<.001). Bromodeoxyuridine incorporation and
      staurosporine-induced apoptosis assays were elevated in fluoxetine-treated cells.
      Quantitative RT-PCR analysis revealed no significant differences in the
      expression of neurotrophic factors, brain-derived neurotrophic factor
      (BDNF);glial-derived neurotrophic factor (GDNF) and cAMP-responsive element
      binding protein (CREB) between cells treated with fluoxetine for two weeks and
      their untreated counterparts. These results may help elucidate the mechanism of
      action of fluoxetine as a therapeutic drug for the treatment of depression. Data
      presented herein provide more evidence that, in addition to having a direct
      chemical effect on serotonin levels, fluoxetine can influence hESC-derived
      neuronal cells by increasing cell proliferation, while allowing them to maintain
      their neuronal characteristics.

PMID- 19598109
TI  - XIV workshop on the development and function of reproductive organs.
AB  - The XIV Workshop on the Development and Function of Reproductive Organs was held
      in Rome, from 14-17 September, 2008, at the Congress Centre of the University of
      Tor Vergata of Villa Mondragone (Rome, Italy). The Workshop was conceived to be a
      survey of the events from the formation of the gamete precursors, the primordial
      germ cells, to the development of the preimplantation embryo through female and
      male gametogenesis in the mouse experimental model. It was divided into six
      topics including classic and highly-debated current subjects in the field of the
      biology of reproduction: mammalian primordial germ cells, the formation of the
      gonads, stem cells and germ cells, gametogenesis from birth to adult (male),
      gametogenesis from birth to adult (female), and finally fertilization and
      preimplantation embryo.

PMID- 19598108
TI  - A novel role for Glucocorticoid-Induced TNF Receptor Ligand (Gitrl) in early
      embryonic zebrafish development.
AB  - Tumour necrosis factor ligand and receptor superfamily (TNFSF and TNFRSF) members
      have diverse and well-studied functions in the immune system. Additional, non
      immunological roles, such as in the morphogenesis of bone, tooth, hair and skin
      have also been described for some members. GITRL and its receptor GITR are well
      described as co-regulators of the mammalian immune response. Here, we describe
      the identification and cloning of their zebrafish homologues and demonstrate a
      novel role for the ligand, but not the receptor, in early vertebrate development.
      The assignment of zebrafish Gitrl and Gitr was supported by homology and
      phylogenetic analysis. The ligand exhibited an oscillating pattern of mRNA
      expression during the first 36 hours post fertilization, during which time gitr
      mRNA was not detected, and morpholino oligonucleotide-mediated knock-down of
      gitrl, but not of gitr, resulted in disruption of early embryogenesis, most
      clearly revealed during gastrulation, which corresponded to the earliest peak in
      gitrl mRNA expression (5.25-10 hpf). We found Stat3 signalling to be altered in
      the gitrl-morphants, suggesting that one possible role for Gitrl during
      embryogenesis may be modulation of Jak/Stat signalling.

PMID- 19598110
TI  - Primordial germ cell biology at the beginning of the XXI century.
AB  - At the XIV Workshop on the Development and Function of the Reproductive Organs
      held at the Congress Centre of the University of Rome Tor Vergata, Monteporzio
      Catone, Rome, Italy, the introduction to the first session entitled Mammalian
      primordial germ cells dedicated to the memory of Anne McLaren, was the occasion
      for a concise review of the state of art of research on the biology of primordial
      germ cells (PGCs). This great, unforgettable scientist, who died in a car
      accident in July 2007, dedicated most of her studies to this field over the last
      25 years. Topics briefly reviewed in this Meeting Report are: 1) how the germ
      line is determined; 2) what are the mechanisms underlying PGC migration; 3) to
      what extent PGC survival, proliferation and differentiation are cell autonomous
      or environmentally controlled processes and 4) how the potential for totipotency
      is retained in PGCs.

PMID- 19598111
TI  - Cell cycle control of Notch signaling and the functional regionalization of the
      neuroepithelium during vertebrate neurogenesis.
AB  - A critical feature of vertebrate neural precursors is the to-and-fro displacement
      of their nuclei as cell cycle progresses, thus giving rise to a pseudostratified
      epithelium. This nuclear behavior, referred to as interkinetic nuclear migration
      (INM), is translated into the disposition of the cell somas at different
      orthogonal levels depending on the cell cycle stage they are. The finding that
      important regulators of neurogenesis, such as the proneural and neurogenic genes,
      undergo cyclic changes of expression and function in coordination with the cell
      cycle and the INM, and that the neurogenic process correlates with a particular
      window of the cell cycle, in coincidence with the apical localization in the
      neuroepithelium of neural precursors, is a novel concept that facilitates our
      understanding of the neurogenic process in vertebrates. As such, recent data
      support the notion that the three-dimensional structure of the neuroepithelium is
      crucial for proper neuronal production. In this review, we describe current
      knowledge of the molecular mechanisms involved in the differential expression and
      function of the proneural and neurogenic gene products along the cell cycle, and
      we discuss important consequences for vertebrate neurogenesis derived from this
      observation.

PMID- 19598112
TI  - Revisiting old vaginal topics: conversion of the Mullerian vagina and origin of
      the "sinus" vagina.
AB  - Vaginal development has been a longstanding controversy, which hampers studies on
      vaginal diseases as well as cervical and uterine diseases. Most concerns center
      on: why is the vaginal epithelium different from the uterine epithelium; and
      where does the vagina originate from? It is commonly held that the rodent vagina
      has a dual origin: the cranial part is derived from the Mullerian duct (Mullerian
      vagina) and the caudal part derived from the urogenital sinus (sinus vagina).
      This concept was deduced from morphological observations. However, it cannot
      explain the difference between the Mullerian vagina and the uterus. Moreover,
      accumulating new data from genetic and molecular studies contradicts the
      urogenital sinus origin of the sinus vagina. The present review summarizes
      previous morphological observations and new findings from genetic and molecular
      studies, and addresses molecular mechanisms underlying the origin and
      organogenesis of the vagina in rodents. It provides evidence to show that the
      whole vagina is derived the Mullerian duct. BMP4 reshapes the intermediate
      mesoderm-derived Mullerian duct into the vaginal primordium. The latter thus
      exhibits different features from the uterus, including the stratified squamous
      epithelium and insensitivity to anti-Mullerian hormone. The sinus vagina is
      formed by extrinsic BMP4-mediated caudal extension of the Mullerian duct. The
      present review thus shows how a century of controversy over the origin and
      organogenesis of the vagina has been resolved. This new understanding will
      provide additional insight into genetic diseases and tumors of the female
      reproductive tract.

PMID- 19598114
TI  - Proteomics analysis of regenerating amphibian limbs: changes during the onset of
      regeneration.
AB  - During amphibian epimorphic limb regeneration, local injury produces metabolic
      changes that lead to cellular dedifferentiation and formation of a blastema, but
      few details of these changes have been elucidated. Here we report the first
      global proteomic analysis of epimorphic regeneration comparing the profiles of
      abundant proteins in larval limbs of the anuran Xenopus laevis (stage 53) at the
      time of amputation (0dPA) and 3 days post-amputation when the regeneration
      blastema is developing (3dPA). We identified and quantified 1517 peptides, of
      which 1067 were identified with high peptide ID confidence. Of these 1067
      proteins, 489 showed significant changes in quantity between the two groups.
      Taking into account identical peptides whose fold changes were within 20%, and
      not including peptides whose fold changes were below the observed fold changes of
      peptides for the internal standard (chicken lysozyme), we were able to identify
      145 peptides elevated in 3dPA relative to 0dPA and 220 peptides in 0dPA relative
      to 3dPA. In this report, we focus on those proteins that were elevated in the
      3dPA tissue relative to 0dPA. In this class were members of the annexin family
      (e.g. ANXA1, ANXA2, ANXA5) and the ANXA2-binding partner S100A10, which have
      important immunoregulatory roles in other systems and were also shown to be
      differentially expressed in stage 53 and 57 3dPA and 5dPA blastemas in our
      previous microarray studies. Besides elucidating the possible modulation of
      inflammation during amphibian limb regeneration, our proteomic study also
      provides insight into dedifferentiation by revealing up-regulation of proteins
      known to characterize many stem cells.

PMID- 19598115
TI  - On the role of Eph signalling in thymus histogenesis; EphB2/B3 and the organizing
      of the thymic epithelial network.
AB  - In the current study, we extend our own previous results on the thymocyte
      phenotype of EphB2 and/or EphB3 deficient mice by analyzing the phenotype and the
      histological organization of their thymic epithelial stroma. All studied adult
      EphB-deficient thymi showed profound alterations with respect to the wild-type
      (WT) ones. Each mutant exhibited a specific phenotype, but also showed common
      features including occurrence of K5+K8+MTS10+ immature medullary epithelial
      cells, numerous K5-K8-MTS20+ cells and K5+K8+ cells in the thymic cortex and
      cortical and medullary K5-K8- areas devoid of epithelial cell markers. In
      addition, comparative analysis of WT and EphB-deficient embryonic and newborn
      thymi demonstrated that the observed adult phenotype was a consequence of the
      gradual accumulation of early phenotypic and morphological defects, becoming more
      severe at the end of embryonic life and in newborn animals. Together, these
      results confirm a role for EphB2 and EphB3 in thymus morphogenesis. The obtained
      data are discussed from the point of view of the recognized role played by these
      two Ephs in the homeostasis of other epithelia and their possible relationships
      with molecules known to be involved in thymic epithelial cell development.

PMID- 19598113
TI  - Identification of regulatory elements in the Isl1 gene locus.
AB  - Isl1 is a LIM/homeodomain transcription factor with critical roles for the
      development of the heart, the nervous system and the pancreas. Both deficiency
      and mis-expression of Isl1 cause profound developmental defects, demonstrating
      the importance of proper regulation of Isl1 gene expression during development.
      In order to understand the mechanisms that control Isl1 expression during
      embryogenesis and in tissue differentiation, we initiated a screen for gene
      regulatory elements in the Isl1 locus using a novel dual reporter gene vector
      that allows screens of large genomic regions through reporter gene assays in
      vitro and in vivo. We identified regions from the Isl1 gene locus that confer
      transcriptional activity in pancreatic cell lines in vitro. Using transgenic
      mice, we furthermore discovered an enhancer with in vivo specificity for the
      developing heart, as well as visceral and posterior mesoderm. Our findings
      further suggest that Foxo1 as well as Gata4 contribute to the activity of this
      enhancer in the developing embryo. We conclude that Isl1 gene expression is
      controlled in modular fashion by several elements with distinct functionality.
      Embryonic Isl1 expression in several tissues of mesodermal origin is driven by a
      specific enhancer that is located 3-6kb downstream of the gene.

PMID- 19598117
TI  - Distribution of p53 binding protein 1 (53BP1) and phosphorylated H2A.X during
      mouse preimplantation development in the absence of DNA damage.
AB  - The cells in the preimplantation mammalian embryo undergo several rounds of fast
      cell division. Whether the known DNA repair pathways are active during these
      early stages of development where cell division is of primary importance, has not
      been fully established. Because of the important role of phosphorylated H2A.X
      (gammaH2A.X) in the DNA damage response as well as its putative role in assembly
      of embryonic chromatin, we analysed its distribution in the preimplantation mouse
      embryo. We found that H2A.X is highly phosphorylated throughout preimplantation
      development in the absence of any induced DNA damage. Moreover, gammaH2A.X levels
      vary significantly throughout the cell cycle. Interestingly, after the 4-cell
      stage, we detected high levels of H2A.X phosphorylation in mitosis, where
      telomeres appeared focally enriched with gammaH2A.X. In contrast, 53BP1, which is
      known to be recruited to DNA damage sites, is undetectable at mitotic chromosomes
      at these stages and its localisation changes upon blastocyst formation from
      mainly nuclear to cytoplasmic. We also show that 53BP1 and gammaH2A.X rarely
      colocalise, suggesting that the high levels of phosphorylation of H2A.X in the
      embryo might not be directly linked to the DNA damage response in the embryo. Our
      data suggest that phosphorylation of H2A.X is an important event in the fast
      dividing cells of the early embryo in the absence of any induced DNA damage. We
      discuss the possible consequences of these findings on the genome-wide chromatin
      remodelling that ocurs in the preimplantation mammalian embryo.

PMID- 19598116
TI  - S. macrurus myogenic regulatory factors (MRFs) induce mammalian skeletal muscle
      differentiation; evidence for functional conservation of MRFs.
AB  - The current-producing cells of the electric organ, i.e., electrocytes, in
      Sternopygus macrurus derive from skeletal muscle fibers. Mature electrocytes are
      not contractile, but they do retain some muscle proteins, are multinucleated, and
      receive cholinergic innervation. Electrocytes express the myogenic regulatory
      factors (MRFs) MyoD, myogenin, Myf5 and MRF4 despite their incomplete muscle
      phenotype. Although S. macrurus MRFs share functional domains which are highly
      conserved and their expression is confined to the myogenic lineage, their
      capability to induce the muscle phenotype has not been determined. To test the
      functional conservation of S. macrurus MRFs to transcriptionally activate
      skeletal muscle gene expression and induce the myogenic program, we transiently
      over-expressed S. macrurus MyoD (SmMyoD) and myogenin (SmMyoG) in mouse
      C3H/10T1/2 and NIH3T3 embryonic cells. RT-PCR and immunolabeling studies showed
      that SmMyoD and SmMyoG can efficiently convert these two cell lines into
      multinucleated myotubes which expressed differentiated muscle markers. The levels
      of myogenic induction by SmMyoD and SmMyoG were comparable to those obtained with
      mouse MRF homologs. Furthermore, SmMyoD and SmMyoG proteins were able to induce
      mouse MyoD and myogenin in C3H/10T1/2 cells. We conclude that S. macrurus MRFs
      are functionally conserved as they can transcriptionally activate skeletal muscle
      gene expression and induce the myogenic program in mammalian non-muscle cells.
      Hence, these data suggest that the partial muscle phenotype of electrocytes is
      not likely due to differences in the MRF-dependent transcriptional program
      between skeletal muscle and electric organ.

PMID- 19598118
TI  - A novel role of the glial fate determinant glial cells missing in hematopoiesis.
AB  - Glial cell deficient/Glial cells missing (Glide/Gcm) transcription factor is
      expressed in all glial precursors of the Drosophila embryo. Gcm is necessary and
      sufficient to induce glial differentiation but also plays a role in other cell
      types, by interacting with specific factors. To find potential partners of Gcm
      which trigger these other pathways, we performed a yeast two-hybrid screen and
      identified dpias, a gene involved in post-embryonic hematopoiesis. dpias larvae
      show melanotic tumors due to excess of lamellocytes, a hemocyte lineage that is
      involved in non-self recognition. We here show that blocking Gcm activity also
      triggers melanotic tumors and that gcm interacts genetically with dpias.
      Moreover, the members of the Janus Kinase (JAK)/ Signal Transducer and Activator
      of Transcription (STAT) pathway, which are known for their role in the vertebrate
      and invertebrate immune system and are required for dpias-dependent tumor
      formation, act downstream of Gcm. Altogether, this study identifies an
      unpredicted role of Gcm, dictated by its cofactor dpias, allowing Gcm to act in a
      specific pathway. Together with the recent finding that glia act as scavengers
      during development and in pathological conditions, our data open new perspectives
      onto the cellular and molecular pathways involved in non-self recognition within
      and outside the nervous system.

PMID- 19598119
TI  - The surface ectoderm of the chick embryo exhibits dynamic variation in its
      response to neurogenic signals.
AB  - The epibranchial placodes are specialized areas of surface ectoderm that make a
      vital contribution to the peripheral nervous system, producing sensory neurons of
      the cranial ganglia. They have long been characterized as a series of patches of
      thickened ectoderm in the vicinity of each pharyngeal cleft. We have previously
      demonstrated that Sox3 is not only expressed in these structures but also marks a
      larger, earlier domain. Here we demonstrate that neurons are produced from the
      Sox3-positive ectoderm that lies outside of the classically-defined epibranchial
      placodes. Our data show that these regions contribute neurons to the cranial
      ganglia, but then cease producing neurons as they lose Sox3 expression. We
      further demonstrate that the ectoderm in these regions is responsive to
      extracellular or intracellular stimuli that initiate aspects of neuronal
      differentiation. This response to neurogenic stimuli is lacking in regions of
      ectoderm distant from the normal sites of neurogenesis and the response to
      constitutively active Bmp receptor in particular, disappears coincident with loss
      of Sox3 expression. Finally, we show that a dominant repressor form of Sox3
      blocks the ability of the ectoderm to undergo neurogenesis. Thus, Sox3 appears to
      be essential for the neurogenic capacity of surface ectoderm exhibited by the
      epibranchial placodes.

PMID- 19598120
TI  - The spatio-temporal pattern of testis organogenesis in mammals - insights from
      the mole.
AB  - Some cellular events are crucial in testis organogenesis, including Sertoli and
      Leydig cell differentiation, mesonephric cell migration and testis cord
      formation. These processes are controlled by transcription factors, paracrine
      signalling and hormones. Using the mole species Talpa occidentalis as an
      alternative animal model, we report the expression patterns of nine genes during
      testis differentiation and analyse their implications in the above-mentioned
      cellular processes. We show that: 1) Sertoli cell differentiation occurs very
      early and precedes mesonephric cell migration, indicating that the latter is not
      needed for the endocrine cytodifferentiation of Sertoli cells; 2) the time of
      Leydig cell differentiation is consistent with the participation of PDGFR-alpha
      in promoting the migration and/or proliferation of Leydig cell precursors, and
      with that of WNT4 signalling in inhibiting Leydig cell differentiation and 3) the
      formation of the tunica albuginea involves intragonadal cell migration/movement.
      These results demonstrate that testicular organogenesis in the mole differs from
      that in the mouse in some particular aspects, thus providing evidence that the
      spatio-temporal pattern of testis development is not highly conserved during
      mammalian evolution.

PMID- 19598121
TI  - Essential validation of gene trap mouse ES cell lines: a test case with the gene
      Ttrap.
AB  - Gene trapping in mouse embryonic stem (ES) cells enables near-saturation vector
      based insertional mutagenesis across the genome of this model organism. About
      135,000 trapped ES cell lines are made available to the scientific community by
      the International Gene Trap Consortium (IGTC; www.genetrap.org). A search of one
      of its databases identified an ES cell line (RRS512) with a betaGeo-based gene
      trap (gt) vector insertion in intron 5 of Ttrap, a gene that encodes an
      intracellular signalling protein, which is implicated in gastrulation movement
      and left-right asymmetry in zebrafish embryos. We have determined the exact gt
      insertion point in the mutant ES cell clone RRS512 and confirmed the production
      of a chimaeric transcript consisting of the upstream Ttrap exons and the gene
      trap vector encoded marker/selection fusion sequences. This ES cell line was used
      to generate heterozygous Ttrap mutant mice, which were further crossed to obtain
      Ttrap(gt/gt) mice. In contrast to Ttraps documented essential role during nodal
      and Smad3 controlled zebrafish early embryogenesis, Ttrap(gt/gt) mice were born
      with a normal Mendelian distribution. However, subsequent analysis of these
      Ttrap(gt/gt) mice has revealed a duplication of the wild-type Ttrap allele that
      was already present in the RRS512 cell line. Based on our detailed analysis
      presented here, we suggest an extensive procedure for the characterization of
      gene trap ES cell lines prior to generating gene trap mice with these.

PMID- 19598122
TI  - A novel method for microinjection into Xenopus eggs and embryos supported in
      methylcellulose solution.
AB  - We have developed a novel method for microinjection into Xenopus eggs and
      embryos. Microinjection was performed into eggs or embryos that were placed in
      wells (ca. 2.5 mm x 2.5 mm x 0.8 mm for each well) at the bottom of a
      commercially available hybridoma dish, which was filled with 1.5% methylcellulose
      solution. Eggs or embryos, rotated to a desired orientation in the viscous
      methylcellulose solution with a hair loop, could remain in the orientation for
      more than twenty minutes. Accordingly, samples such as mRNAs, DNAs, proteins and
      antisense morpholino oligonucleotides could be easily and efficiently
      microinjected into any part (animal, vegetal, dorsal, lateral or ventral) of more
      than five hundred eggs and embryos in one day. In addition, methylcellulose did
      not interfere with the development of the injected eggs and embryos.

PMID- 19598124
TI  - Expression of CAP2 during early Xenopus embryogenesis.
AB  - We have cloned and characterized a second member of the Xenopus CAP (cyclase
      associated protein) gene family. xCAP2 demonstrates greater restriction of
      expression than its homolog, xCAP1, and is differentially expressed throughout
      early embryogenesis. Although present as a maternal transcript, CAP2 comes to be
      expressed in the anterior-most mesoderm/endoderm during late gastrulation, in
      paraxial mesoderm during late neurula stages, and later expresses in lens,
      cardiac primordia, somites, otic vesicles, retina, and in the optic and
      craniofacial musculature. The gene is also expressed in the leading edge of
      myotome.

PMID- 19598123
TI  - Cloning and functional characterization of the intersex homologous gene in the
      pest lepidopteron Maruca vitrata.
AB  - The intersex (ix) gene works in concert with doublesex (dsx) at the bottom of the
      sex-determination hierarchy to control somatic sexual differentiation in
      Drosophila melanogaster females. Here we report the isolation and
      characterization of the Drosophila intersex (ix) homologue in the pest
      lepidopteron Maruca vitrata (Mvix). The Mvix gene exhibits major complexity with
      respect to the Drosophila homolog. It is expressed in males and females and its
      pre-mRNA is subject to differential splicing events which affect both the protein
      coding and the non-coding regions. Moreover, Northern blot experiments revealed
      the presence of a female-specific transcript in pupae RNA, which appears to be
      the first described sex specific transcript of ix homologs characterized to date.
      The expression of Mvix cDNA in D.melanogaster transgenic flies indicates that the
      MvIX product, which shares a relatively high degree of homology with the
      D.melanogaster IX protein, is able to partially rescues the Drosophila mutant
      phenotype.

PMID- 19598125
TI  - Dynamic expression pattern of distinct genes in the presomitic and somitic
      mesoderm during Xenopus development.
AB  - Whole-mount and sectioned in situ hybridization was used to identify genes with
      restricted expression pattern in the presomitic and somitic mesoderm during
      Xenopus early development. Here we report the dynamic expression pattern of six
      distinct genes differentially expressed in these regions. These include Xenopus
      homologues of purine nucleoside phosphorylase, acetylcholine receptor, aspartate
      aminotransferase, glycine amidinotransferase and brain and muscle isoform
      creatine kinases. Purine nucleoside phosphorylase was initially expressed in the
      marginal zone at gastrula stage and then localized to the tail bud. Although the
      other genes showed no significantly localized expression at gastrula or neurula
      stages, they are progressively restricted in the somitic mesoderm as development
      proceeds. A common feature for these genes is that their deficiency in humans
      leads to an impairment of several tissue or cell functions. An analysis of their
      expression pattern could provide information regarding their implication in early
      development.

PMID- 19598126
TI  - Expression of prohormone convertase 2 and the generation of neuropeptides in the
      developing nervous system of the gastropod Haliotis.
AB  - Prohormone convertase 2 (PC2) belongs to a family of enzymes involved in the
      proteolytic maturation of neuropeptide precursors into mature peptides that act
      as neurotransmitters, neuromodulators or neurohormones. Here we show that a gene
      encoding a PC2-like enzyme (HasPC2) is expressed during larval development and in
      the adult ganglia of the vetigastropod Haliotis asinina. HasPC2 exhibits high
      sequence identity to other gastropod PC2s and thus is likely to function in
      peptide processing. Analysis of HasPC2 expression indicates that it is activated
      early in nervous system development. During trochophore and early veliger larval
      stages, HasPC2 is expressed in the vicinity of the forming ganglia of the central
      nervous system and parts of the putative peripheral nervous system. Later in
      larval development, at the time the veliger becomes competent to interact with
      the external environment and initiate metamorphosis, HasPC2 expression largely
      restricts to cells of the major ganglia and their commissures. Profiling of
      veliger larvae by bioinformatic approaches suggests the expression of a variety
      of peptides. Direct MALDI-MS-based peptide profiling of juvenile Haliotis
      cerebral ganglia (brain) reveals an abundance of neuropeptides, including
      FMRFamide-related peptides and APGWamide, compatible with PC2 functioning in
      neuropeptide processing in these regions. These results are consistent with PC2
      regulating neuropeptide generation in the earliest functioning of the gastropod
      nervous system.

PMID- 19598127
TI  - Expression of a Prrxl1 alternative splice variant during the development of the
      mouse nociceptive system.
AB  - BACKGROUND: Gene expression can be differentially regulated by alternatively
      spliced transcription factors, providing a mechanism for precise control of
      diverse morphogenetic events. The paired-type homedomain transcription factor
      Prrxl1 (formerly known as Drg11) was described as a key regulator of the
      differentiation of the spinal cord neuronal circuit dedicated to the processing
      of nociceptive information. Here, we report the characterization of a Prrxl1
      alternative splice variant that we termed Prrxl1-b. METHODS: Mouse Prrxl1 isoform
      mRNA sequences were obtained by Rapid Amplification cDNA Ends (RACE) analysis.
      The distribution and the amount of Prrxl1-b at different developmental ages were
      analyzed by in situ hybridization and quantitative real-time PCR, and compared
      with those of Prrxl1. RESULTS: The amount of Prrxl1 was higher than that of the
      Prrxl1-b isoform both in the DRG and the spinal cord. Prrxl1-b contains the N
      terminal homeodomain but differs from the previously identified Prrxl1 in the C
      terminal part due to alternative mRNA processing. This results in the lack of the
      OAR domain in the Prrxl1-b primary structure. Prrxl1-b is exclusively localized
      in neurons primarily involved in the processing of the pain somatosensory
      modality. Prrxl1-b presents the same regional distribution pattern as Prrxl1, but
      differs as to the qualitative and quantitative expression profile at distinct
      developmental ages in the dorsal root ganglion and spinal cord. CONCLUSION: We
      suggest that the tissue-specific role of the Prrxl1 gene may be sustained by an
      accurate balance in the ratio between the amount of Prrxl1 and its OAR-lacking
      variant, Prrxl1-b, which may be critical during nociceptive circuit development.

PMID- 19598128
TI  - CBP/p300 and associated transcriptional co-activators exhibit distinct expression
      patterns during murine craniofacial and neural tube development.
AB  - Mutations in each of the transcriptional co-activator genes - CBP, p300, Cited2,
      Cart1 and Carm1 - result in neural tube defects in mice. The present study thus
      furnishes a complete and comparative temporal and spatial expression map of
      CBP/p300 and associated transcriptional co-activators, Cited2, Cart1 and Carm1
      during the period of murine neural tube development (embryonic days 8.5 to 10.5).
      Each co-activator except Cart1 was expressed in the dorsal neural folds on E8.5.
      Although CBP and p300 are functionally interchangeable in vitro, their respective
      expression patterns diverge during embryogenesis before neural fold fusion is
      complete. CBP gene expression was lost from the neural folds by E8.75 and was
      thereafter weakly expressed in the maxillary region and limb buds, while p300
      exhibited strong expression in the first branchial arch, limb bud and
      telencephalic regions on E9.5. Cart1 exhibited strong expression in the forebrain
      mesenchyme from E9.0 through E10.5. Although CBP, p300, Carm1 and Cited2 share
      temporal expression on E8.5, these co-activators have different spatial
      expression in mesenchyme and/or the neuroepithelium. Nevertheless, co
      localization to the dorsal neural folds on E8.5 suggests a functional role in
      elevation and/or fusion of the neural folds. Target genes, and pathways that
      promote cranial neural tube fusion that are activated by
      CBP/p300/Carm1/Cited2/Cart1-containing transcriptional complexes await
      elucidation.

PMID- 19598129
TI  - Expression of Wnts in the developing murine secondary palate.
AB  - Morphogenesis of the mammalian secondary palate requires coordination of cell
      migration, proliferation, differentiation, apoptosis and synthesis of
      extracellular matrix molecules by numerous signal transduction pathways. Recent
      evidence suggests a role for members of the Wnt family of secreted cytokines in
      orofacial development. However, no study has systematically or comprehensively
      examined the expression of Wnts in embryonic orofacial tissue. We thus conducted
      a survey of the expression of all known Wnt genes in the developing murine
      secondary palate. Using an RT-PCR strategy to assay gene expression, 12 of the 19
      known members of the Wnt family were found to be expressed in embryonic palatal
      tissue during key phases of its development. The expression of 5 Wnt family
      members was found to be temporally regulated. Moreover, these Wnts had unique
      spatio-temporal patterns of expression which suggested possible roles in palatal
      ontogeny.

PMID- 19598130
TI  - Heterologous expression of DsRed2 in young sponges (Porifera).
AB  - Sponges (Porifera) are currently considered to be the first branch off the
      Urmetazoa, common ancestors of all multicellular animals or metazoa. Research in
      the field of the developmental biology of sponges was restricted to morphological
      observations. Nowadays, research is mainly concentrated on larval development,
      primarily dealing with tissue formation. Already since 1907, methods for
      developing functional sponges from stem cells have been at hand. Functional
      freshwater sponges can be grown from stem cell populations originating from
      gemmulae. A number of poriferan sequences with high similarity to regulative
      genes in higher metazoa have already been found. We have now succeeded in
      heterologously expressing the red fluorescent protein DsRedN1 under the control
      of the cytomegalovirus promoter in young specimens of the freshwater sponge
      Spongilla lacustris. The protein folded correctly, polymerized and subsequently
      was detected by fluorescence microscopy. Reporting this expression system, we now
      consider this appealing system for early meatazoan development to be ready for
      molecular developmental biology and functional genetics research.

PMID- 19598131
TI  - Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan
      synthesis and expression of growth factor-related genes in human nucleus pulposus
      cell line.
AB  - Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to effect
      differentiation and activation of human chondrocytes. A study involving
      stimulation of rabbit disc cells with LIPUS revealed upregulation of cell
      proliferation and proteoglycan (PG) synthesis. However, the effect of LIPUS on
      human nucleus pulposus cells has not been investigated. In the present study,
      therefore, we investigated whether LIPUS stimulation of a human nucleus pulposus
      cell line (HNPSV-1) exerted a positive effect on cellular activity. HNPSV-1 cells
      were encapsulated in 1.2% sodium alginate solution at 1x10(5) cells/ml and
      cultured at 10 beads/well in 6-well plates. The cells were stimulated for 20 min
      each day using a LIPUS generator, and the effects of LIPUS were evaluated by
      measuring DNA and PG synthesis. Furthermore, mRNA expression was analyzed by cDNA
      microarray using total RNA extracted from the cultured cells. Our study revealed
      no significant difference in cell proliferation between the control and the
      ultrasound treated groups. However, PG production was significantly upregulated
      in HNPSV cells stimulated at intensities of 15, 30, 60, and 120 mW/cm(2) compared
      with the control. The results of cDNA array showed that LIPUS significantly
      stimulated the gene expression of growth factors and their receptors (BMP2, FGF7,
      TGFbetaR1 EGFRF1, VEGF). These findings suggest that LIPUS stimulation
      upregulates PG production in human nucleus pulposus cells by the enhancement of
      several matrix-related genes including growth factor-related genes. Safe and non
      invasive stimulation using LIPUS may be a useful treatment for delaying the
      progression of disc degeneration.

PMID- 19598132
TI  - [Analysis: impact factor and scientific communication].

PMID- 19598133
TI  - [The clinical relevance of FDG-PET imaging in severe traumatic brain injuries].
AB  - AIM: To evaluate the usefulness of positron emission tomography (PET) as a
      predictor of long-term disability after a severe traumatic brain injury (TBI).
      PATIENTS AND METHODS: Fifty-six patients who had sustained a severe TBI were
      assessed with a broad battery of cognitive and functional scales at baseline and
      6-months after inclusion in a multidisciplinary rehabilitation program. All
      patients underwent a FDG-PET at baseline. A physician blind to clinical data
      performed a semiquantitative analysis (normal vs altered) of functional
      neuroimaging (PET), including four cortical and three subcortical areas. The
      total number of lesions (cortical, subcortical and total) was correlated to the
      intensity of the TBI and to clinical data at admission and at follow-up. RESULTS:
      All patients showed changes in cerebral metabolism, being the thalamus the area
      most frequently affected. The degree of cerebral hypometabolism showed a
      significant correlation with TBI severity, functional disability, global outcome
      and cognitive impairment not only at baseline but also at follow-up. CONCLUSIONS:
      According to our results, FDG-PET may be a useful tool when studying brain
      dysfunction after severe TBI. FDG-PET findings correlate with the TBI severity,
      and with the level of patients' disability, as well as with the degree of memory
      and intelligence impairment. However, clinical variables related to the severity
      of the TBI, still are the best predictors of functional outcome after TBI.

PMID- 19598135
TI  - [Psychomotor profile of children between 5 and 12 years of age, clinically
      diagnosed with attention deficit hyperactivity disorder in Colombia].
AB  - INTRODUCTION: One of the comorbid alterations of attention deficit hyperactivity
      disorder (ADHD) affects motricity, to the point where the quality of motor
      performance during the first 5-6 years of life could constitute a predictor of
      the later appearance of symptoms of the disorder. Moreover, the association
      between motor clumsiness and ADHD results in a poorer prognosis of the condition.
      Nevertheless, few studies have examined the evolution of motricity in children
      affected with this pathology. AIM: To characterise the psychomotor profile of
      children between 5 and 12 years of age who were clinically diagnosed with ADHD in
      the town of Manizales (Colombia) and to compare it with healthy children of the
      same age. SUBJECTS AND METHODS: A cross-sectional descriptive study was conducted
      with a sample of 846 children (422 diagnosed with ADHD and 424 healthy controls).
      RESULTS: Although the values for all the motricity factors were within ranges
      that are considered to be normal, they were significantly poorer (p < 0.000) in
      diagnosed children at all ages. CONCLUSIONS: The psychomotor profile of children
      diagnosed with ADHD was eupraxic and is classified within the same category as
      the healthy children, although quantitatively it was lower.

PMID- 19598134
TI  - [The effectiveness of gravitational valves in the prevention of over-drainage in
      adult patients with hydrocephalus].
AB  - AIM: To evaluate the effect of gravitational valves on over-drainage in
      hydrocephalus in adults. PATIENTS AND METHODS: We performed a retrospective study
      of the shunt systems placed in patients over the age of 18 years between 1998 and
      2006. Patients were divided into two groups: non-GV group (without gravitational
      valve) and GV group (with a gravitational valve, Aesculap-Miethke 5/35). The
      complications that occurred during the first year following the placement of the
      shunt system were recorded. RESULTS: Of a total of 137 patients, 91 were from the
      non-GV group and 46 belonged to the GV group. Mean age: non-GV group, 62.1 years;
      and GV group, 64.2 years, without any significant differences. In 80 patients the
      aetiology was chronic adult hydrocephalus, 19 were due to expansive processes, 15
      due to vascular causes, eight pseudo tumours, six post-traumatic injuries and
      nine were due to other causes. In the non-GV group, 9.89% presented over
      drainage, whereas there were no cases in the GV group; the difference was
      statistically significant (p = 0.029). In the rest of the complications there
      were no significant differences between the two groups. The total complications
      in the non-GV group were 25.27% and in the GV group, 6.52%, and there were
      significant differences (p = 0.01), although, above all, at the expense of over
      drainage, because if this complication was excluded, then the differences were no
      longer significant (p = 0.175). CONCLUSIONS: In our series, the use of
      gravitational valves in the prevention of over-drainage in adult hydrocephalus
      proved to be more effective than employing valves without the gravitational
      device.

PMID- 19598136
TI  - [PANDAS with a chorea-like clinical presentation and associated autoimmune
      pathology: a case report].
AB  - INTRODUCTION: The disorder known as 'PANDAS syndrome' (paediatric autoimmune
      neuro-psychiatric disorders associated with Streptococci) consists in an abrupt
      onset of obsessive-compulsive symptoms and/or movement disorders, a pre-puberal
      onset, and an episodic course. Antibiotic therapy has been postulated as a first
      choice therapeutic option. A summarised review of main literature on this topic
      is presented. CASE REPORT: A girl, 10 years and 6 months old, with a dramatic
      clinical onset of a chorea-like and obsessive-compulsive symptomathology with a
      remarkable improvement after 10 days penicillin p.o. intake. She has a positive
      family history of autoimmune disorders, with elevated anti-phospholipidic
      antibodies. CONCLUSION: The implications of the case follow-up with many
      relapses, the development of a diabetes after corticoid therapy and the elevated
      anti glutamic dexcarboxilasa (anti-GAD) are discussed regarding a common
      underlying autoimmune mechanism.

PMID- 19598137
TI  - [Diseases caused by triplet expansion].
AB  - INTRODUCTION: Today we know of a group of mutations caused by the expansion of
      nucleotide triplets, which are very unstable in meiosis and mitosis. Four types
      of triplets have the capacity for pathogenic expansion in human beings (CGG/ GCC,
      CAG/GTC, CTG/GAC and GAA/CTT) and maybe located both in coding sequences
      (bulbospinal muscular atrophy, Huntington's disease and certain spinocerebellar
      ataxias) and non-coding sequences (fragile X syndrome, Friedreich's ataxia,
      myotonic dystrophy). Trinucleotide expansion may lead to gains or losses in gene
      functioning and seems to be associated to a variety of factors, some of which are
      directly related with the expansive process (cis-acting) and others whose
      interaction with the triplets helps to make them increasingly more unstable
      (trans-acting). Medium-sized expansions (pre-mutations), although clinically
      silent, do show a marked tendency to expand into complete mutations during the
      transition along the germinal line. The models that have been proposed to explain
      triplet expansion involve gene recombination and replication processes; however,
      they have not fully succeeded in explaining the phenomena related to mutation or
      phenotypic expression in these diseases. DEVELOPMENT: This work examines the most
      recent concepts related to the dynamic mutation processes that give rise to human
      diseases; it also reviews the most important clinico-biological aspects observed
      in those diseases. CONCLUSIONS: Dynamic mutation processes represent a new
      concept in the molecular biology of gene mutations. An ever increasing number of
      pathologies are caused by this type of DNA alterations, which, as a whole,
      display very interesting clinico-biological characteristics.

PMID- 19598138
TI  - [Lipoprotein-associated phospholipase A(2) and stroke].
AB  - INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme
      member of A2 phosholipases superfamily. The 80% circulates bound to LDL
      cholesterol and levels of both parameters are positively correlated. The main
      function of this enzyme is to hydrolyze oxidized phospholipids contained in LDL
      cholesterol forming pro-inflammatory products in atheroma plaque. Several studies
      related raised Lp-PLA2 and vascular risk. AIM: To review available data relating
      Lp-PLA2 and stroke. DEVELOPMENT: Different cohorts and cases and controls studies
      showed an association between higher levels of Lp-PLA2 and the risk of suffering:
      first cardiovascular event (coronary heart disease, ischemic stroke) or its
      recurrence; progression of coronary damage evaluated using cardiac computed
      tomography; or death of cardiovascular cause. Published risk measurements are
      less than 2 and it has been demonstrated that raised levels of enzyme are risk
      factor independent of classic cardiovascular risk factors and non-HDL cholesterol
      and C-reactive protein levels. The clinical data and the knowledge of the role of
      Lp-PLA2 in plaque destabilization justified the development of inhibitor drugs.
      CONCLUSIONS: According to current evidence, patients in the higher range of Lp
      PLA2 may be considerate at higher risk of suffering a vascular event. The
      application to stroke needs a better definition of the pathophysiologic role and
      the knowledge of phase II clinical trials currently under development in coronary
      heart disease.

PMID- 19598139
TI  - [The beginnings of neuroscience in Spain. 'Neural circulation' in the work of the
      illustrious novator Martin Martinez (1684-1734)].
AB  - INTRODUCTION: During the 'scientific revolution' that took place in the 18th
      century, a complex and poorly completed theory on the functioning of the nervous
      system, neural circulation, was to draw the attention of the European vanguards
      and, although it came up against a number of important obstacles, it also
      attempted to renew the traditional gallenic knowledge that had prevailed until
      then. In Spain, the field of medical knowledge was to flourish and the
      neurosciences presented their credentials with the introduction and development
      of the concept of neural circulation by the novator Martin Martinez. DEVELOPMENT:
      This work attempts to evoke that historic time and to summarise the elements that
      go to make up the neural or 'spirituous' circulation, as well as reviewing the
      figure of Martin Martinez. CONCLUSIONS: Neural circulation was a speculative
      theoretical deviation that tried, unsuccessfully, to offer a better explanation
      for empirical facts. In Spain, led by Martin Martinez, it was at least an attempt
      to modernise thinking by introducing the new ideas about neurological anatomy
      that were going round Europe.

PMID- 19598140
TI  - [Radiological findings in intracranial hypotension syndrome].

PMID- 19598142
TI  - [Lesion in the basal ganglia and brain stem compatible with neuro-Behcet's
      disease].

PMID- 19598143
TI  - [Cooking in dreams: a peculiar side effect of zolpidem].

PMID- 19598144
TI  - [18q syndrome associated with blepharospasm].

PMID- 19598145
TI  - Performance of new gellan gum hydrogels combined with human articular
      chondrocytes for cartilage regeneration when subcutaneously implanted in nude
      mice.
AB  - Gellan gum is a polysaccharide that has been recently proposed by our group for
      cartilage tissue-engineering applications. It is commonly used in the food and
      pharmaceutical industry and has the ability to form stable gels without the use
      of harsh reagents. Gellan gum can function as a minimally invasive injectable
      system, gelling inside the body in situ under physiological conditions and
      efficiently adapting to the defect site. In this work, gellan gum hydrogels were
      combined with human articular chondrocytes (hACs) and were subcutaneously
      implanted in nude mice for 4 weeks. The implants were collected for histological
      (haematoxylin and eosin and Alcian blue staining), biochemical [dimethylmethylene
      blue (GAG) assay], molecular (real-time PCR analyses for collagen types I, II and
      X, aggrecan) and immunological analyses (immunolocalization of collagen types I
      and II). The results showed a homogeneous cell distribution and the typical round
      shaped morphology of the chondrocytes within the matrix upon implantation.
      Proteoglycans synthesis was detected by Alcian blue staining and a statistically
      significant increase of proteoglycans content was measured with the GAG assay
      quantified from 1 to 4 weeks of implantation. Real-time PCR analyses showed a
      statistically significant upregulation of collagen type II and aggrecan levels in
      the same periods. The immunological assays suggest deposition of collagen type II
      along with some collagen type I. The overall data shows that gellan gum hydrogels
      adequately support the growth and ECM deposition of human articular chondrocytes
      when implanted subcutaneously in nude mice.

PMID- 19598147
TI  - Non-pecuniary returns to higher education: the effect on smoking intensity in the
      UK.
AB  - This paper investigates whether higher education (HE) produces non-pecuniary
      returns via a reduction in the intensity of consumption of health-damaging
      substances. In particular, it focuses on current smoking intensity of the British
      individuals sampled in the 29-year follow-up survey of the 1970 British Cohort
      Study. We estimate endogenous dummy ordinal response models for cigarette
      consumption and show that HE is endogenous with respect to smoking intensity and
      that even when endogeneity is accounted for, HE is found to have a strong
      negative effect on smoking intensity. Moreover, pecuniary channels, such as
      occupation and income, mediate only a minor part of the effect of HE. Our results
      are robust to modelling individual self-selection into current smoking
      participation (at age 29) and to estimating a dynamic model in which past smoking
      levels affect current smoking levels.

PMID- 19598148
TI  - Estimating incubation period distributions with coarse data.
AB  - The incubation period, the time between infection and disease onset, is important
      in the surveillance and control of infectious diseases but is often coarsely
      observed. Coarse data arises because the time of infection, the time of disease
      onset or both are not known precisely. Accurate estimates of an incubation period
      distribution are useful in real-time outbreak investigations and in modeling
      public health interventions. We compare two methods of estimating such
      distributions. The first method represents the data as doubly interval-censored.
      The second introduces a data reduction technique that makes the computation more
      tractable. In a simulation study, the methods perform similarly when estimating
      the median, but the first method yields more reliable estimates of the
      distributional tails. We conduct a sensitivity analysis of the two methods to
      violations of model assumption and we apply these methods to historical
      incubation period data on influenza A and respiratory syncytial virus. The
      analysis of reduced data is less computationally intensive and performs well for
      estimating the median under a wide range of conditions. However for estimation of
      the tails of the distribution, the doubly interval-censored analysis is the
      recommended procedure.

PMID- 19598149
TI  - Increments of alpha-dystroglycan expression in liver metastasis correlate with
      poor survival in gastric cancer.
AB  - BACKGROUND: Dystroglycan (DG) is a recently focused adhesion molecule with
      possible roles in cancer development and progression. We investigated
      correlations between alpha-DG expression and prognosis in gastric carcinoma with
      liver metastasis. METHODS: For 40 patients with gastric adenocarcinoma and liver
      only metastasis, alpha-DG expression was determined by immunohistochemistry in
      paraffin-embedded surgical specimens of resected stomach tumor, resected liver
      metastasis, and their normal counterpart tissues. Correlations between alpha-DG
      expression and prognosis were retrospectively analyzed. RESULTS: alpha-DG
      expression was higher in primary gastric cancer (P = 0.006) and lower in liver
      metastasis (P = 0.002) than in each normal counterpart. In primary stomach
      cancer, patients who had lower alpha-DG expression in tumors than in normal
      counterparts showed poor overall survival (OS) (P = 0.028). In contrast, in the
      liver, patients who had higher alpha-DG expression in tumors than in normal
      counterparts showed poor OS (P = 0.022). Also, higher alpha-DG expression in
      liver metastasis than in stomach tumors led to poor recurrence-free survival (P =
      0.023) and OS (P = 0.056). CONCLUSIONS: This approach may be used to further
      understanding of the pathogenesis of liver metastasis from gastric cancer.
      Further studies are warranted to reveal the mechanisms of alpha-DG dysregulation
      in liver metastasis.

PMID- 19598150
TI  - Technical feasibility and safety of laparoscopy-assisted total gastrectomy in
      gastric cancer: a comparative study with laparoscopy-assisted distal gastrectomy.
AB  - BACKGROUND AND OBJECTIVE: Only a few surgeons with much experience of
      laparoscopic surgery perform laparoscopy-assisted total gastrectomy (LATG),
      because of its technical difficulty and concern about subsequent complications.
      The aim of this study was to evaluate the technical feasibility and safety of
      LATG as compared with laparoscopy-assisted distal gastrectomy (LADG) in gastric
      cancer. METHODS: From January 2002 to December 2007, LADG was performed in 473
      patients and LATG in 67 patients at the Korean National Cancer Center. Surgical
      procedures and short-term surgical outcomes of LATG were analyzed. RESULTS: D2
      lymph node dissection was performed in 35 LATG (52.2%) cases and in 274 LADG
      (57.9%) cases (P = 0.378). Mean blood losses during operation were 156.8 +/-
      158.0 ml and 190.7 +/- 176.2 ml, respectively (P = 0.114). The open conversion
      rate for LATG was higher than LADG without significance (4.3% vs. 1.7%, P =
      0.153). Complications occurred in 18 LATG cases (26.9%) and 38 LADG cases (8.0%)
      (P < 0.001). The most common postoperative complication of LATG was anastomotic
      stricture after esophagojejunostomy. CONCLUSIONS: LATG is a technically feasible
      procedure as compared with LADG. However, its postoperative complication rate is
      higher than that of LADG, especially that of anastomotic stricture. A more
      effective anastomotic method during LATG is required to prevent stricture.

PMID- 19598151
TI  - Prominent system of RFamide immunoreactive neurons in the rhopalia of box
      jellyfish (Cnidaria: Cubozoa).
AB  - The four visual sensory structures of a cubomedusa, the rhopalia, display a
      surprisingly elaborate organization by containing two lens eyes and four
      bilaterally paired pigment cup eyes. Peptides containing the peptide sequence Arg
      Phe-NH2 (RFamide) occur in close association with visual structures of
      cnidarians, including the rhopalia and rhopalial stalk of cubomedusae, suggesting
      that RFamide functions as a neuronal marker for certain parts of the visual
      system of medusae. Using immunofluorescence we give a detailed description of the
      organization of the RFamide-immunoreactive (ir) nervous system in the rhopalia
      and rhopalial stalk of the cubomedusae Tripedalia cystophora and Carybdea
      marsupialis. The bilaterally symmetric RFamide-ir nervous system contains four
      cell groups and three morphologically different cell types. Neurites spread
      throughout the rhopalia and occur in close vicinity of the pigment cup eyes and
      the lower lens eye. Two commissures connect the two sides of the system and
      neurites of one rhopalial cell group extend into the rhopalial stalk. The RFamide
      ir nervous system in the rhopalia of cubomedusae is more widespread and comprises
      more cells than earlier discerned. We suggest that the system might not only
      integrate visual input but also signals from other senses. One of the RFamide-ir
      cell groups is favorably situated to represent pacemaker neurons that set the
      swimming rhythm of the medusa.

PMID- 19598157
TI  - Protein nitration during defense response in Arabidopsis thaliana.
AB  - Nitric oxide and reactive oxygen species play a key role in the plant
      hypersensitive disease resistance response, and protein tyrosine nitration is
      emerging as an important mechanism of their co-operative interaction. Up to now,
      the proteins targeted by this post-translational modification in plants are still
      totally unknown. In this study, we analyzed for the first time proteins
      undergoing nitration during the hypersensitive response by analyzing via 1D- and
      2D-western blot the protein extracts from Arabidopsis thaliana plants challenged
      with an avirulent bacterial pathogen (Pseudomonas syringae pv. Tomato). We show
      that the plant disease resistance response is correlated with a modulation of
      nitration of proteins involved in important cellular process, such as
      photosynthesis, glycolysis and nitrate assimilation. These findings shed new
      light on the signaling functions of nitric oxide and reactive oxygen species,
      paving the way on studies on the role of this post-translational modification in
      plants.

PMID- 19598158
TI  - Effective elimination of nucleic acids from bacterial protein samples for
      optimized blue native polyacrylamide gel electrophoresis.
AB  - Nucleic acids remaining within bacterial protein samples from Streptomyces
      lividans and Escherichia coli were found to interfere significantly with blue
      native polyacrylamide gel electrophoresis (BN-PAGE), a technique used frequently
      for analyzing bacterial protein complexes in proteomics studies. We have used
      ultracentrifugation and/or precipitation of cell lysates with streptomycin
      sulfate to eliminate nucleic acids from total and/or membrane protein samples.
      Nucleic acid-binding proteins were first enriched by precipitation with
      streptomycin sulfate, and contaminating nucleic acids were then eliminated by
      precipitation by adding polyethyleneimine. The performance of BN-PAGE was found
      to be dramatically improved by these sample preparation steps.

PMID- 19598160
TI  - Resistive switching and metallic-filament formation in Ag(2)S nanowire
      transistors.

PMID- 19598161
TI  - Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic
      therapy.
AB  - Near-infrared (NIR)-to-visible up-conversion fluorescent nanoparticles have
      potential to be used for photodynamic therapy (PDT) in deep tissue because NIR
      light can penetrate thick tissue due to weak absorption in the optical window.
      Here a uniform layer of mesoporous silica is coated onto NaYF(4) up-converting
      nanocrystals, with a large surface area of approximately 770 m(2) g(-1) and an
      average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is
      incorporated into the mesoporous silica. Upon excitation by a NIR laser, the
      nanocrystals convert NIR light to visible light, which further activates the
      photosensitizer to release reactive singlet oxygen to kill cancer cells. The
      photosensitizer encapsulated in mesoporous silica is protected from degradation
      in the harsh biological environment. It is demonstrated that the photosensitizers
      loaded into the porous silica shell of the nanoparticles are not released out of
      the silica while they continuously produce singlet oxygen upon excitation by a
      NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in
      the silica are removed by soaking in ethanol.

PMID- 19598162
TI  - Stretching the stamp: a flexible approach to the fabrication of miniaturized DNA
      arrays.

PMID- 19598163
TI  - Glycin-bonded silica monolithic column as zwitterionic stationary phase for
      hydrophilic interaction pressurized capillary electrochromatography.
AB  - A novel zwitterionic monolith was prepared by in situ covalent attachment of
      glycin to a gamma-glycidoxypropyltrimethoxysilane-modified silica monolith. The
      monolith possessing in its structure bonded secondary amine groups and carboxylic
      acid groups was evaluated in pressurized CEC (pCEC) system using small neutral
      and charged solutes. Owing to the zwitterionic nature of the resulting stationary
      phase, the direction and magnitude of EOF in this column could be manipulated by
      adjusting the pH values of the mobile phase. Typical hydrophilic interaction was
      observed when the ACN content exceeded 45%. Separations of acidic and basic
      compounds were performed on the prepared column in weakly anodic and cathodic EOF
      modes, respectively. The organic solvent composition, the salt concentration, and
      the pH of the mobile phase have effects on the electrochromatographic retention.
      Besides the hydrophilic interaction and electrophoretic mechanism, electrostatic
      interactions are also involved in the separations of acids and bases on the
      zwitterionic column.

PMID- 19598164
TI  - Monolithic poly(1,2-bis(p-vinylphenyl)ethane) capillary columns for simultaneous
      separation of low- and high-molecular-weight compounds.
AB  - Monolithic poly(1,2-bis(p-vinylphenyl)ethane (BVPE)) capillary columns were
      prepared by thermally initiated free radical polymerisation of 1,2-bis(p
      vinylphenyl)ethane in the presence of inert diluents (porogens) and alpha,alpha'
      azoisobutyronitrile (AIBN) as initiator. Polymerisations were accomplished in 200
      microm ID fused silica capillaries at 65 degrees C and for 60 min. Mercury
      intrusion porosimetry measurements of the polymeric RP support showed a broad
      bimodal pore-size-distribution of mesopores and small macropores in the range of
      5-400 nm and flow-channels in the mum range. N(2)-adsorption (BET) analysis
      resulted in a tremendous enhancement of surface area (101 m(2)/g) of BVPE
      stationary phases compared to typical organic monoliths (approximately 20
      m(2)/g), indicating the presence of a considerable amount of mesopores.
      Consequently, the adequate proportion of both meso- and (small) macropores
      allowed the rapid and high-resolution separation of low-molecular-weight
      compounds as well as biomolecules on the same monolithic support. At the same
      time, the high fraction of flow-channels provided enhanced column permeability.
      The chromatographic performance of poly(1,2-bis(p-vinylphenyl)ethane) capillary
      columns for the separation of biomolecules (proteins, oligonucleotides) and small
      molecules (alkyl benzenes, phenols, phenons) are demonstrated in this article.
      Additionally, pressure drop versus flow rate measurements of novel poly(1,2-bis(p
      vinylphenyl)ethane) capillary columns confirmed high mechanical robustness, low
      swelling in organic solvents and high permeability. Due to the simplicity of
      monolith fabrication, comprehensive studies of the retention and separation
      behaviour of monolithic BVPE columns resulted in high run-to-run and batch-to
      batch reproducibilities. All these attributes prove the excellent applicability
      of monolithic poly(1,2-bis(p-vinylphenyl)ethane) capillary columns for micro-HPLC
      towards a huge range of analytes of different chemistries and molecular sizes.

PMID- 19598165
TI  - Comparison between monolithic and particle-packed platinum C18 columns in HPLC
      determination of acidic and basic test mixtures.
AB  - Herein we report the results of a comparative study on the performance of
      Monolithic RP-18e and Platinum C(18) 3 mum columns for isocratic separation of
      acidic and basic test compounds. The inter- and intraday precision of different
      practical parameters including number of theoretical plates (N), capacity factor
      (K'), tailing factor (T(0.05)), and resolution (R(s)) were determined for both
      columns. Two different production batches were used for each column and batch to
      batch reproducibility of both columns was evaluated. The column backpressure drop
      over flow rate range 0.5-2 mL/min at the monolithic columns was two- to three
      times lower than that on the platinum column without loss of the column
      efficiency. The plate heights were used to estimate the columns efficiency using
      Van Deemter plots. Both types of columns were able to separate the tested
      compounds well with sufficient resolution and peak symmetry but they differ in
      the analysis time and column backpressure, significantly. Monolithic column was
      more convenient as it enables the analytical run under low backpressure at
      shorter time with sufficient separation efficiency.

PMID- 19598167
TI  - Calpain inhibitors prevent p38 MAPK activation and germ cell apoptosis after heat
      stress in pubertal rat testes.
AB  - Testicular injuries like torsion or cryptorchidism can cause massive germ cell
      death, which could have great impact on male reproductive health. In addition, it
      has been proposed that modern life style, in the form of underwear or sedentary
      work position, could increase the testicular temperature, induce germ cell
      apoptosis, reduce spermatozoa quality and promote male infertility. In this work
      we showed that a heat stress stimulus induced massive germ cells apoptosis, which
      was associated with p38 mitogen-activated protein kinase (MAPK) phosphorylation
      along with an increase in the levels of mRNA encoding calpain 2. Synthetic
      calpain inhibitors prevented heat stress-induced germ cell apoptosis through
      inhibition of p38 MAPK phosphorylation. Thus, our results indicate that the
      blockage of calpains suppresses p38 MAPK phosphorylation, and identifies calpain
      activation (most likely calpain 2) as an early event in heat stress-induced male
      germ cell apoptosis.

PMID- 19598166
TI  - Purification of large plasmids with methacrylate monolithic columns.
AB  - The rapid evolution of gene therapy and DNA vaccines results in an increasing
      interest in producing large quantities of pharmaceutical grade plasmid DNA. Most
      current clinical trials involve plasmids of 10 kb or smaller in size, however,
      future requirements for multigene vectors including extensive control regions may
      require the production of larger plasmids, e. g., 20 kb and bigger. The objective
      of this study was to examine certain process conditions for purification of large
      plasmids with the size of up to 93 kb. Since there is a lack of knowledge about
      production and purification of bigger plasmid DNA, cell lysis and storage
      conditions were investigated. The impact of chromatographic system and
      methacrylate monolithic column on the degradation of plasmid molecules under
      nonbinding conditions at different flow rates was studied. Furthermore, capacity
      measurements varying salt concentration in loading buffer were performed and the
      capacities up to 13 mg of plasmid per mL of the monolithic column were obtained.
      The capacity flow independence in the range from 130 to 370 cm/h was observed.
      Using high resolution monolithic column the separation of linear and supercoiled
      isoforms of large plasmids was obtained. Last but not least, since the baseline
      separation of RNA and pDNA was achieved, the one step purification on larger CIM
      DEAE 8 mL tube monolithic column was performed and the fractions were analyzed by
      CIM analytical monolithic columns.

PMID- 19598168
TI  - Mass defect filter technique and its applications to drug metabolite
      identification by high-resolution mass spectrometry.
AB  - Identification of drug metabolites by liquid chromatography/mass spectrometry
      (LC/MS) involves metabolite detection in biological matrixes and structural
      characterization based on product ion spectra. Traditionally, metabolite
      detection is accomplished primarily on the basis of predicted molecular masses or
      fragmentation patterns of metabolites using triple-quadrupole and ion trap mass
      spectrometers. Recently, a novel mass defect filter (MDF) technique has been
      developed, which enables high-resolution mass spectrometers to be utilized for
      detecting both predicted and unexpected drug metabolites based on narrow, well
      defined mass defect ranges for these metabolites. This is a new approach that is
      completely different from, but complementary to, traditional molecular mass- or
      MS/MS fragmentation-based LC/MS approaches. This article reviews the mass defect
      patterns of various classes of drug metabolites and the basic principles of the
      MDF approach. Examples are given on the applications of the MDF technique to the
      detection of stable and chemically reactive metabolites in vitro and in vivo.
      Advantages, limitations, and future applications are also discussed on MDF and
      its combinations with other data mining techniques for the detection and
      identification of drug metabolites.

PMID- 19598169
TI  - Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone
      forming effect via differential mitogen activated protein kinase (MAPK)
      signaling.
AB  - Following a lead obtained from stem-bark extract of Butea monosperma, two
      structurally related methoxyisoflavones; cajanin and isoformononetin were studied
      for their effects in osteoblasts. Cajanin had strong mitogenic as well as
      differentiation-promoting effects on osteoblasts that involved subsequent
      activation of MEK-Erk and Akt pathways. On the other hand, isoformononetin
      exhibited potent anti-apoptotic effect in addition to promoting osteoblast
      differentiation that involved parallel activation of MEK-Erk and Akt pathways.
      Unlike genistein or daidzein, none of these two compounds appear to act via
      estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30
      consecutive days was given to recently weaned female Sprague-Dawley rats with
      each of these compounds at 10.0 mg kg(-1) day(-1) dose. Cajanin increased bone
      mineral density (BMD) at all skeletal sites studied, bone biomechanical strength,
      mineral apposition rate (MAR) and bone formation rate (BFR), compared with
      control. BMD levels at various anatomic positions were also increased with
      isoformononetin compared with control however, its effect was less potent than
      cajanin. Isoformononetin had no effect on the parameters of bone biomechanical
      strength although it enhanced MAR and BFR compared with control. Isoformononetin
      had very mild uterotrophic effect, whereas cajanin was devoid of any such effect.
      Our data suggest that cajanin is more potent than isoformononetin in accelerating
      peak bone mass achievement. To the best of our knowledge, this work represents
      the first attempt to elucidate structure-activity relationship between the two
      methoxylated isoflavones regarding their effects in osteoblasts and bone
      formation.

PMID- 19598170
TI  - Compartmentalization in the triceps brachii motoneuron nucleus and its relation
      to muscle architecture.
AB  - Each fascicle of the triceps brachii (TB) can be independently recruited during
      movement execution. To investigate the anatomical basis of this selective control
      and to gain insight into its functional role in adult rats, we carried out a
      triple retrograde tracing of the motoneurons (MNs) innervating each TB head, and
      performed muscle ATPase histochemistry and histology to correlate the size of the
      MN pools with the number and type of muscle fibers innervated. No double-labeled
      MNs were found, demonstrating that each TB head is innervated by a completely
      independent MN subnucleus. Absolute cell counts determined that the long fascicle
      had the largest MN subnucleus, followed by the medial and the lateral fascicles.
      MNs of the three fascicles intermingled extensively in the rostral part of the
      spinal motor column, while the caudal part of the column comprised mostly MNs
      innervating the long fascicle. Muscle histology and average innervation ratios
      estimated from absolute MN counts showed that the medial head was predominantly
      formed by small type I fibers and motor units (69 fibers/MN). In contrast, the
      lateral fascicle comprised a great quantity of large type IIb fibers and motor
      units (179 fibers/MN), whereas the long head consisted of a more balanced mixture
      of fiber types and motor units (99 fibers/MN). Taking into account the mechanical
      and physiological heterogeneity of the TB, our findings suggest that each
      fascicle may be considered an independent muscle with specific functional roles.

PMID- 19598171
TI  - Optical coherence tomography in biophotonics.

PMID- 19598174
TI  - Ex vivo [11C]-(+)-PHNO binding is unchanged in animal models displaying increased
      high-affinity states of the D2 receptor in vitro.
AB  - Dopamine (DA) D2 receptor supersensitivity has been linked to an increase in the
      density of the D2 high-affinity state as measured in vitro. The two- affinity
      state model of the D2 receptor predicts that the ex vivo specific binding of
      [11C]-(+)-PHNO, an agonist radiotracer thought to bind selectively to the high
      affinity state in vivo, should be increased in animal models that display in
      vitro increases in the proportion of receptors in the D2 high-affinity state.
      Here, we test this hypotheses by comparing the ex vivo SBR of [11C]-(+)-PHNO with
      that of the antagonist radiotracer [3H]-raclopride in three dopaminergically
      supersensitive rat models-AMPH-sensitized rats, rats withdrawn from chronic
      ethanol, and unilaterally 6-OHDA-lesioned rats-using ex vivo dual-radiotracer
      biodistribution studies. We find that in AMPH-sensitized rats and rats withdrawn
      from chronic ethanol treatment, models that exhibited approximately 4-fold
      increases in the D2 high-affinity state in vitro, the SBRs of [11C]-(+)-PHNO and
      [3H]-raclopride are unchanged relative to control rats. In unilaterally 6-OHDA
      lesioned rats, we find that the increase in [11C]-(+)-PHNO SBR is no different
      than that observed for the antagonist radiotracer [3H]-raclopride (54% +/- 16%
      and 52% +/- 14%, respectively). In addition, the effect of acute AMPH
      pretreatment (4 mg/kg, i.v.) on the SBRs of [11C]-(+)-PHNO and [3H]-raclopride is
      equivalent in AMPH-sensitized (-38% +/- 12% and -36% +/- 8%, respectively) and in
      control rats (-40% +/- 11% and -38% +/- 7%). These data emphasize a significant
      discrepancy between in vitro and in vivo measures of D2 agonist binding,
      indicating that the two-affinity-state model of the D2 receptor may not apply
      veridically to living systems. The potential implications of this discrepancy are
      discussed.

PMID- 19598175
TI  - Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are
      prevented in mice lacking dopamine D4 receptors.
AB  - The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal
      cortex, a brain area that integrates motor, rewarding, and cognitive information.
      Because participation of D4Rs in executive learning is largely unknown, we
      challenged D4R knockout mice (Drd4(-/-)) and their wild-type (WT) littermates,
      neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant
      learning paradigms. A continuous reinforcement task, in which one food-pellet was
      delivered after every lever press, showed that 6-OHDA-treated mice
      (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than
      normodopaminergic WT mice. In contrast, Drd4(-/-) mice displayed increased lever
      pressing rates, regardless of their dopamine content. In another study, mice were
      trained to solve an operant two-choice task in which a first showing lever was
      coupled to the delivery of one food pellet only after a second lever emerged.
      Interval between presentation of both levers was initially 12 s and progressively
      shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet
      reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic
      WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs
      was not detrimental in this task. Moreover, hypodopaminergic Drd4(-/-) mice were
      as efficient as their normodopaminergic Drd4(-/-) siblings in selecting the
      reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments
      to retrieve rewards in two operant positive reinforcement tasks, but these
      deleterious effects are totally prevented in the absence of functional D4Rs.

PMID- 19598176
TI  - A practical approach for exploration and modeling of the design space of a
      bacterial vaccine cultivation process.
AB  - A licensed pharmaceutical process is required to be executed within the validated
      ranges throughout the lifetime of product manufacturing. Changes to the process,
      especially for processes involving biological products, usually require the
      manufacturer to demonstrate that the safety and efficacy of the product remains
      unchanged by new or additional clinical testing. Recent changes in the
      regulations for pharmaceutical processing allow broader ranges of process
      settings to be submitted for regulatory approval, the so-called process design
      space, which means that a manufacturer can optimize his process within the
      submitted ranges after the product has entered the market, which allows flexible
      processes. In this article, the applicability of this concept of the process
      design space is investigated for the cultivation process step for a vaccine
      against whooping cough disease. An experimental design (DoE) is applied to
      investigate the ranges of critical process parameters that still result in a
      product that meets specifications. The on-line process data, including near
      infrared spectroscopy, are used to build a descriptive model of the processes
      used in the experimental design. Finally, the data of all processes are
      integrated in a multivariate batch monitoring model that represents the
      investigated process design space. This article demonstrates how the general
      principles of PAT and process design space can be applied for an undefined
      biological product such as a whole cell vaccine. The approach chosen for model
      development described here, allows on line monitoring and control of cultivation
      batches in order to assure in real time that a process is running within the
      process design space.

PMID- 19598177
TI  - Clinical optical coherence tomography combined with multiphoton tomography of
      patients with skin diseases.
AB  - We report on the first clinical study based on optical coherence tomography (OCT)
      in combination with multiphoton tomography (MPT) and dermoscopy. 47 patients with
      a variety of skin diseases and disorders such as skin cancer, psoriasis,
      hemangioma, connective tissue diseases, pigmented lesions, and autoimmune bullous
      skin diseases have been investigated with (i) state-of-the-art OCT systems for
      dermatology including multibeam swept source OCT, (ii) the femtosecond laser
      multiphoton tomograph, and (iii) dermoscopes. Dermoscopy provides two-dimensional
      color images of the skin surface. OCT images reflect modifications of the
      intratissue refractive index whereas MPT is based on nonlinear excitation of
      endogenous fluorophores and second harmonic generation. A stack of cross
      sectional OCT "wide field" images with a typical field of view of 5 x 2 mm(2)
      gave fast information on the depth and the volume of the lesion. Multiphoton
      tomography provided 0.36 x 0.36 mm(2) horizontal/diagonal optical sections within
      seconds of a particular region of interest with superior submicron resolution
      down to a tissue depth of 200 mum. The combination of OCT and MPT provides a
      unique powerful optical imaging modality for early detection of skin cancer and
      other skin diseases as well as for the evaluation of the efficiency of
      treatments.

PMID- 19598178
TI  - Differential corticosteroid receptor regulation of mesoaccumbens dopamine efflux
      during the peak and nadir of the circadian rhythm: a molecular equilibrium in the
      midbrain?
AB  - Corticosteroid receptor modulation of mesoaccumbens dopamine neurotransmission is
      believed to be a key neurobiological mechanism mediating the effects of stress in
      addiction. Importantly, nucleus accumbens (NAc) subregions (core and shell) are
      reported to respond differentially to fluctuating basal levels of
      glucocorticoids, with dopaminergic responses in the core of the NAc being
      somewhat impervious to fluctuating levels of glucocorticoids relative to the
      shell. To investigate the corticosteroid receptor mechanisms mediating basal
      dopamine efflux in the core of the NAc, we have used chronoamperometry in
      combination with stearate-modified graphite paste electrodes in urethane
      anesthetized male Long-Evans rats during the peak and nadir of the circadian
      cycle. Blockade of ventral tegmental area low-affinity glucocorticoid (GR) or
      high-affinity mineralocorticoid (MR) receptors with mifepristone (1
      microg/microl) or spironolactone (0.2 microg/microl), respectively, indicated
      that endogenous phase-dependent corticosteroid receptor activation (GRs during
      peak; MRs during nadir) facilitated extracellular NAc dopamine efflux.
      Conversely, the alternate receptor's actions appeared inhibitory at these time
      points (MRs during peak; GRs during nadir). Pharmacological activation of either
      the GR or MR with corticosterone (2 microg/microl) or aldosterone (0.2
      microg/microl), respectively, potentiated NAc dopamine efflux, irrespective of
      circadian phase. Together, these data suggest that dominant corticosteroid
      receptor activation stimulates tonic mesoaccumbens dopamine transmission,
      enabling MRs and GRs to differentially maintain basal NAc dopamine release over
      the course of the circadian cycle. This points to an important molecular
      mechanism through which relatively stable NAc core dopamine extracellular levels
      could be maintained in the face of fluctuating corticosterone circadian rhythms.

PMID- 19598179
TI  - Cardiac phenotyping in ex vivo murine embryos using microMRI.
AB  - Microscopic MRI (microMRI) is an emerging technique for high-throughput
      phenotyping of transgenic mouse embryos, and is capable of visualising
      abnormalities in cardiac development. To identify cardiac defects in embryos, we
      have optimised embryo preparation and MR acquisition parameters to maximise image
      quality and assess the phenotypic changes in chromodomain helicase DNA-binding
      protein 7 (Chd7) transgenic mice. microMRI methods rely on tissue penetration
      with a gadolinium chelate contrast agent to reduce tissue T(1), thus improving
      signal-to-noise ratio (SNR) in rapid gradient echo sequences. We investigated
      15.5 days post coitum (dpc) wild-type CD-1 embryos fixed in gadolinium-diethylene
      triamine pentaacetic acid (Gd-DTPA) solutions for either 3 days (2 and 4 mM) or 2
      weeks (2, 4, 8 and 16 mM). To assess penetration of the contrast agent into heart
      tissue and enable image contrast simulations, T(1) and T(*) (2) were measured in
      heart and background agarose. Compared to 3-day, 2-week fixation showed reduced
      mean T(1) in the heart at both 2 and 4 mM concentrations (p < 0.0001), resulting
      in calculated signal gains of 23% (2 mM) and 29% (4 mM). Using T(1) and T(*) (2)
      values from 2-week concentrations, computer simulation of heart and background
      signal, and ex vivo 3D gradient echo imaging, we demonstrated that 2-week fixed
      embryos in 8 mM Gd-DTPA in combination with optimised parameters
      (TE/TR/alpha/number of averages: 9 ms/20 ms/60 degrees /7) produced the largest
      SNR in the heart (23.2 +/- 1.0) and heart chamber contrast-to-noise ratio (CNR)
      (27.1 +/- 1.6). These optimised parameters were then applied to an MRI screen of
      embryos heterozygous for the gene Chd7, implicated in coloboma of the eye, heart
      defects, atresia of the choanae, retardation of growth, genital/urinary
      abnormalities, ear abnormalities and deafness (CHARGE) syndrome (a condition
      partly characterised by cardiovascular birth defects in humans). A ventricular
      septal defect was readily identified in the screen, consistent with the human
      phenotype.

PMID- 19598180
TI  - BOLD-specific cerebral blood volume and blood flow changes during neuronal
      activation in humans.
AB  - To understand and predict the blood-oxygenation level-dependent (BOLD) fMRI
      signal, an accurate knowledge of the relationship between cerebral blood flow
      (DeltaCBF) and volume (DeltaCBV) changes is critical. Currently, this
      relationship is widely assumed to be characterized by Grubb's power-law, derived
      from primate data, where the power coefficient (alpha) was found to be 0.38. The
      validity of this general formulation has been examined previously, and an alpha
      of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism
      change (DeltaCMRo(2)) using calibrated BOLD. However, the direct use of this
      relationship has been the subject of some debate, since it is well established
      that the BOLD signal is primarily modulated by changes in 'venous' CBV
      (DeltaCBV(v), comprising deoxygenated blood in the capillary, venular, and to a
      lesser extent, in the arteriolar compartments) instead of total CBV, and yet
      DeltaCBV(v) measurements in humans have been extremely scarce. In this work, we
      demonstrate reproducible DeltaCBV(v) measurements at 3 T using venous refocusing
      for the volume estimation (VERVE) technique, and report on steady-state
      DeltaCBV(v) and DeltaCBF measurements in human subjects undergoing graded visual
      and sensorimotor stimulation. We found that: (1) a BOLD-specific flow-volume
      power-law relationship is described by alpha = 0.23 +/- 0.05, significantly lower
      than Grubb's constant of 0.38 for total CBV; (2) this power-law constant was not
      found to vary significantly between the visual and sensorimotor areas; and (3)
      the use of Grubb's value of 0.38 in gradient-echo BOLD modeling results in an
      underestimation of DeltaCMRo(2).

PMID- 19598181
TI  - The association between socioeconomic status and exposure to mobile
      telecommunication networks in children and adolescents.
AB  - A potential association between socioeconomic status (SES) and self-reported use
      of mobile phones has been investigated in a few studies. If measured exposure to
      mobile phone networks differs by SES in children, it has not yet been studied.
      Interview data of 1,481 children and 1,505 adolescents on participants' mobile
      phone use, socio-demographic characteristics and potential confounders were taken
      from the German MobilEe-study. Sociodemographic data was used to stratify
      participants into three "status groups" (low, middle, high). Using a personal
      dosimeter, we obtained an exposure profile over 24 h for each of the
      participants. Exposure levels during waking hours were expressed as mean
      percentage of the reference level. Children with a low SES were more likely to
      own a mobile phone (OR 2.1; 95% CI: 1.1-3.9) and also reported to use their
      mobile phone longer per day (OR 2.4; 95% CI: 1.1-5.4) than children with a high
      SES. For adolescents, self-reported duration of mobile phone use per day was also
      higher with a low SES (OR: 3.4; 95% CI: 1.4-8.4) compared with a high SES. No
      association between SES and measured exposure to mobile telecommunication
      networks was seen for children or adolescents. Mobile phone use may differ
      between status groups with higher use among disadvantaged groups. However, this
      does not result in higher overall exposure to mobile telecommunication networks.
      Whether short duration of own mobile phone use or the small numbers of
      participants with a low SES are causal, have to be investigated in further
      studies.

PMID- 19598182
TI  - Design of potent 9-mer antimicrobial peptide analogs of protaetiamycine and
      investigation of mechanism of antimicrobial action.
AB  - Protaetiamycine is an insect defensin, a naturally occurring 43-amino-acid
      residue antimicrobial peptide derived from the larvae of the beetle Protaetia
      brevitarsis. In a previous work that aimed at developing short antibiotic
      peptides, we designed 9-mer peptide analogs of protaetiamycine. Among them,
      RLWLAIGRG-NH2 showed good antifungal activity against Candida albicans. In this
      study, we designed four 9-mer peptide analogs based on the sequence of RLWLAIGRG
      NH2, in which Gly or Ile was substituted with Arg, Lys, or Trp to optimize the
      balance between the hydrophobicity and cationicity of the peptides and to
      increase bacterial cell selectivity. We measured their toxicity to bacteria and
      mammalian cells as well as their ability to permeabilize model phospholipid
      membranes. Substitution of Arg for Gly9 at the C-terminus (9Pbw1) resulted in two
      to fourfold improvement in antibacterial activity. Further substitution of Gly7
      with Lys (9Pbw2 and 9Pbw4) caused four- to eightfold improvement in the
      antibacterial activity without increase in cytotoxocity, while substitution of
      Gly7 with Trp (9Pbw3) increased cytotoxicity as well as antibacterial activity.
      The peptides 9Pbw2 and 9Pbw4 with the highest bacterial cell selectivity were not
      effective in depolarizing the membrane of Staphylococcus aureus cytoplasmic
      membranes and showed almost no leakage of a fluorescent dye entrapped within the
      vesicles. Gel-retardation experiments indicated that 9Pbw2 and 9Pbw4 inhibited
      the migration of DNA at concentrations >20 microM. Three positively charged
      residues at the C-terminus in 9Pbw2 and 9Pbw4 may facilitate effective
      penetration into the negatively charged phospholipid membrane of bacteria. The
      results obtained in this study suggest that the bactericidal action of our potent
      antibacterial peptides, namely 9Pbw2 and 9Pbw4, may be attributed to the
      inhibition of the functions of intracellular components after penetration of the
      bacterial cell membrane.

PMID- 19598183
TI  - Estimating variance parameters from multivariate normal variables subject to
      limit of detection: MLE, REML, or Bayesian approaches?
AB  - Likelihood-based approaches, which naturally incorporate left censoring due to
      limit of detection, are commonly utilized to analyze censored multivariate normal
      data. However, the maximum likelihood estimator (MLE) typically underestimates
      variance parameters. The restricted maximum likelihood estimator (REML), which
      corrects the underestimation of variance parameters, cannot be easily extended to
      analyze censored multivariate normal data. In the light of the connection between
      the REML and a Bayesian approach discovered in 1974 by Dr Harville, this paper
      describes a Bayesian approach to censored multivariate normal data. This Bayesian
      approach is justified through its link to the REML via Laplace's approximation
      and its performance is evaluated through a simulation study. We consider the
      Bayesian approach as a valuable alternative because it yields less biased
      variance parameter estimates than the MLE, and because a solid REML is
      technically difficult when data are left censored.

PMID- 19598184
TI  - Structural studies on the reaction of isopenicillin N synthase with a sterically
      demanding depsipeptide substrate analogue.
AB  - Isopenicillin N synthase (IPNS) is a nonheme iron(II)-dependent oxidase that
      catalyses the central step in penicillin biosynthesis, conversion of the
      tripeptide delta-L-alpha-aminoadipoyl-L-cysteinyl-D-valine (ACV) to isopenicillin
      N (IPN). This report describes mechanistic studies using the analogue delta-(L
      alpha-aminoadipoyl)-(3S-methyl)-L-cysteine D-alpha-hydroxyisovaleryl ester
      (A(S)mCOV), designed to intercept the catalytic cycle at an early stage. A(S)mCOV
      incorporates two modifications from the natural substrate: the second and third
      residues are joined by an ester, so this analogue lacks the key amide of ACV and
      cannot form a beta-lactam; and the cysteinyl residue is substituted at its beta
      carbon, bearing a (3S)-methyl group. It was anticipated that this methyl group
      will impinge directly on the site in which the co-substrate dioxygen binds. The
      novel depsipeptide A(S)mCOV was prepared in 13 steps and crystallised with IPNS
      anaerobically. The 1.65 A structure of the IPNS-Fe(II)-A(S)mCOV complex reveals
      that the additional beta-methyl group is not oriented directly into the oxygen
      binding site, but does increase steric demand in the active site and increases
      disorder in the position of the isovaleryl side chain. Crystals of IPNS-Fe(II)
      A(S)mCOV were incubated with high-pressure oxygen gas, driving substrate turnover
      to a single product, an ene-thiol/C-hydroxylated depsipeptide. A mechanism is
      proposed for the reaction of A(S)mCOV with IPNS, linking this result to previous
      crystallographic studies with related depsipeptides and solution-phase
      experiments with cysteine-methylated tripeptides. This result demonstrates that a
      (3S)-methyl group at the substrate cysteinyl beta-carbon is not in itself a block
      to IPNS activity as previously proposed, and sheds further light on the steric
      complexities of IPNS catalysis.

PMID- 19598185
TI  - A new type of pyrrolidine biosynthesis is involved in the late steps of
      xenocoumacin production in Xenorhabdus nematophila.

PMID- 19598187
TI  - Probing liquid-liquid interfaces with spatially resolved NMR spectroscopy.

PMID- 19598186
TI  - Amyloids go genomic: insights regarding the sequence determinants of prion
      formation from genome-wide studies.

PMID- 19598188
TI  - A ferromagnetic [Cu3(OH)2]4+ cluster formed inside a tritopic
      nonaazapyridinophane: crystal structure and solution studies.

PMID- 19598189
TI  - The transmembrane structure of integrin alphaIIbbeta3: significance for signal
      transduction.

PMID- 19598190
TI  - Chemical and physical solutions for hydrogen storage.
AB  - Hydrogen is a promising energy carrier in future energy systems. However, storage
      of hydrogen is a substantial challenge, especially for applications in vehicles
      with fuel cells that use proton-exchange membranes (PEMs). Different methods for
      hydrogen storage are discussed, including high-pressure and cryogenic-liquid
      storage, adsorptive storage on high-surface-area adsorbents, chemical storage in
      metal hydrides and complex hydrides, and storage in boranes. For the latter
      chemical solutions, reversible options and hydrolytic release of hydrogen with
      off-board regeneration are both possible. Reforming of liquid hydrogen-containing
      compounds is also a possible means of hydrogen generation. The advantages and
      disadvantages of the different systems are compared.

PMID- 19598191
TI  - Highly stereoselective one-pot synthesis of bicyclic isoxazolidines with five
      stereogenic centers by an organocatalytic process.

PMID- 19598192
TI  - Rhodium-catalyzed enantioselective and diastereoselective hydrogenation of beta
      ketoenamides: efficient access to anti 1,3-amino alcohols.

PMID- 19598193
TI  - Phase transition induced adhesion of giant unilamellar vesicles.
AB  - Cell and vesicle adhesion is believed to be dictated by the balance between a
      local interaction potential, which represents the sum of all attractive and
      repulsive forces and the elastic energy. Changing the mechanical properties of
      the membrane therefore offers a sensitive tool to control vesicle adhesion. Here,
      we take advantage of the dramatic changes in area per molecule, fluidity and
      compressibility during lipid phase transition to alter vesicle adhesion. We
      demonstrate that driving a giant unilamellar vesicle (GUV) through its phase
      transition by increasing the temperature leads to a wetting transition of the
      vesicle onto a pure glass substrate. Analysing vesicle shape and the adhesion
      area shows that the vesicle is strongly adhered and that the wetting process
      follows exactly the melting transition of the lipid membrane. We provide evidence
      that the linear relationship between change in area and enthalpy during lipid
      phase transition can be applied to individual vesicles as its application
      correctly extracts the heat capacity profile of DPPC vesicles from our adhesion
      experiments. It clearly demonstrates that this wetting process is driven by the
      coupling of mechanical and thermodynamic properties in lipid membranes.

PMID- 19598194
TI  - Phospholipid bilayers supported on thiolate-covered nanostructured gold: in situ
      Raman spectroscopy and electrochemistry of redox species.
AB  - Thiol-covered nanostructured gold has been tested as a platform for the
      preparation of high-area phospholipid bilayer systems suitable for optical and
      electrochemical sensing. In situ and ex situ Raman spectroscopy and
      electrochemical measurements are made to study methylene blue (MB) and flavin
      adenine dinucleotide (FAD) incorporation into dimyristoylphosphatidylcholine
      (DMPC) bilayers prepared by vesicle fusion on dithiothreitol (DTT)-covered
      nanostructured gold. Results show that lipophilic positively charged MB molecules
      are incorporated in the bilayer reaching the DTT-gold interface. On the other
      hand, the negatively charged FAD molecules are immobilized at the outer part of
      the phospholipid bilayer and cannot be electrochemically detected. Our results
      demonstrate that DTT-covered nanostructured gold provides a suitable high-area
      platform for phospholipid membranes that are able to separate and sense different
      kinds of molecules and biomolecules.

PMID- 19598195
TI  - A comparative study of the structural, electronic, and vibrational properties of
      NH3BH3 and LiNH2BH3: theory and experiment.
AB  - Herein, we systematically investigate the structural, electronic, and vibrational
      properties of ammonia borane (NH(3)BH(3), AB) and lithium amidoborane
      (LiNH(2)BH(3,) LAB) through both density functional calculations and experiments.
      AB and LAB samples are generated and their vibrational spectra are obtained by
      using Fourier transformed infrared spectroscopy (FTIR). The measured vibrational
      spectra are in good agreement with the calculated ones. Our calculations show
      that the Li-related vibration modes are primarily found in the low-frequency
      region (<1000 cm(-1)), and that the intermolecular interactions significantly
      influence the vibrational spectra. Electronic structure calculations provide
      insights into the differences between the binding natures of AB and LAB and their
      influence on the vibrational properties of these compounds.

PMID- 19598196
TI  - Towards x-ray absorption spectroscopy in real time.

PMID- 19598197
TI  - Benzo- and naphthoborepins: blue-emitting boron analogues of higher acenes.

PMID- 19598198
TI  - Indium-based perovskites: a new class of near-room-temperature multiferroics.

PMID- 19598200
TI  - Carbohydrate-derived 1,3-diphosphite ligands as chiral nanoparticle stabilizers:
      promising catalytic systems for asymmetric hydrogenation.
AB  - Metallic Ru, Rh, and Ir nanoparticles were prepared by the decomposition of
      organometallic precursors under H(2) pressure in the presence of 1,3-diphosphite
      ligands, derived from carbohydrates, as stabilizing agents. Structural
      modifications to the diphosphite backbone were found to influence the
      nanoparticles' size, dispersion, and catalytic activity. In the hydrogenation of
      o- and m-methylanisole, the Rh nanoparticles showed higher catalytic activity
      than the corresponding Ru nanoparticles. The Ir nanoparticles presented the
      lowest catalytic activity of the series. In all cases, the hydrogenation of o
      methylanisole gave total selectivity for the cis-product, however, the ee of the
      product was always less than 6 %. A maximum of 81 % cis-selectivity was obtained
      for the hydrogenation of m-methylanisole, however, no asymmetric induction was
      observed. These results show that the catalytic activity is affected by a
      combination of influences from the substrate, the diphosphite ligands, and the
      metallic nanoparticles.

PMID- 19598201
TI  - Tuning the composition of guest molecules in clathrate hydrates: NMR
      identification and its significance to gas storage.
AB  - Gas hydrates represent an attractive way of storing large quantities of gas such
      as methane and carbon dioxide, although to date there has been little effort to
      optimize the storage capacity and to understand the trade-offs between storage
      conditions and storage capacity. In this work, we present estimates for gas
      storage based on the ideal structures, and show how these must be modified given
      the little data available on hydrate composition. We then examine the hypothesis
      based on solid-solution theory for clathrate hydrates as to how storage capacity
      may be improved for structure II hydrates, and test the hypothesis for a
      structure II hydrate of THF and methane, paying special attention to the
      synthetic approach used. Phase equilibrium data are used to map the region of
      stability of the double hydrate in P-T space as a function of the concentration
      of THF. In situ high-pressure NMR experiments were used to measure the kinetics
      of reaction between frozen THF solutions and methane gas, and (13)C MAS NMR
      experiments were used to measure the distribution of the guests over the cage
      sites. As known from previous work, at high concentrations of THF, methane only
      occupies the small cages in structure II hydrate, and in accordance with the
      hypothesis posed, we confirm that methane can be introduced into the large cage
      of structure II hydrate by lowering the concentration of THF to below 1.0 mol %.
      We note that in some preparations the cage occupancies appear to fluctuate with
      time and are not necessarily homogeneous over the sample. Although the tuning
      mechanism is generally valid, the composition and homogeneity of the product vary
      with the details of the synthetic procedure. The best results, those obtained
      from the gas-liquid reaction, are in good agreement with thermodynamic
      predictions; those obtained for the gas-solid reaction do not agree nearly as
      well.

PMID- 19598199
TI  - Nucleotide-catalyzed conversion of racemic zeolite-type zincophosphate into
      enantioenriched crystals.

PMID- 19598202
TI  - Observation of the properties of a single unit of a limited CDW structure in a
      Pt(II)/Pt(IV) host-guest binary system based on a square-shaped complex.
AB  - A macrocyclic tetranuclear platinum(II) complex [Pt(en)(4,4'-bpy)](4)(NO(3))(8)
      (1(NO(3))(8); en = ethylenediamine, 4,4'-bpy = 4,4'-bipyridine) and a mononuclear
      platinum(IV) complex [Pt(en)(2)Br(2)]Br(2) (2Br(2)) formed two kinds of
      Pt(II)/Pt(IV) mixed valence assemblies when reacted: a discrete host-guest
      complex 12Br(10) (3) and an extended 1-D zigzag sheet 1(2)(3)Br(8)(NO(3))(6) (4).
      Single crystal X-ray analysis showed that the dimensions of the assemblies could
      be stoichiometrically controlled. Resonance Raman spectra suggested the presence
      of an intervalence interaction, which is typically observed for quasi-1-D halogen
      bridged M(II)/M(IV) complexes. The intervalence interaction indicates the
      presence of an isolated {Pt(II)X-Pt(IV)-XPt(II)} moiety in the structure of 4. On
      the basis of electronic spectra and polarized reflectance measurements, we
      conclude that 4 exhibits intervalence charge transfer (IVCT) bands. A Kramers
      Kronig transformation was carried out to obtain an optical conductivity spectrum,
      and two sub-bands corresponding to slightly different Pt(II)-Pt(IV) distances
      were observed.

PMID- 19598203
TI  - Conjugated polyelectrolytes as new platforms for drug screening.
AB  - In recent years, conjugated polyelectrolytes (CPEs) have attracted increasing
      attention for their applications in highly sensitive biosensors by taking
      advantage of their unique optical amplification properties. In comparison to
      previous applications tailored for highly sensitive biomacromolecule detection,
      this Focus Review highlights recent research efforts in the development of water
      soluble CPEs as a new class of optical platforms for the screening of potential
      drugs. Three types of biological targets for the search of small-molecule active
      drugs are described: nucleic acids, enzymes, and RNA-protein complexes. Future
      research directions for drug screening based on CPEs are also presented.

PMID- 19598204
TI  - Cell encapsulation within PVA-based hydrogels via freeze-thawing: a one-step
      scaffold formation and cell storage technique.
AB  - Cryogelation is a physical hydrogel formation method for certain polymers,
      notably polyvinyl alcohol (PVA). The hypothesis of this study is that a PVA-based
      solution with the necessary intracellular cryoprotectant and nutrient supply can
      be used, first for storage of vascular smooth muscle cells, and subsequently to
      form a suitable tissue-engineering scaffold during the thawing process. Bovine
      arterial smooth muscle cells were encapsulated within PVA-gelatin hydrogels over
      a wide range of serum, DMSO and cell culture medium concentrations. Several
      parameters expected to affect gelation and cell viability (PVA viscosity, DMSO
      concentration, serum presence) were assessed with experimental designs and the
      optimal conditions for cell survival were determined. Cell viability can be
      improved by increasing concentration of DMSO and serum without compromising the
      gelation process. An additional crosslinking step using a coagulation bath was
      beneficial for hydrogel stability but caused peripheral accumulation of cells. In
      conclusion, a freeze-thaw process can be utilized to prepare and store cell-laden
      hydrogels with adjustable mechanical properties.

PMID- 19598205
TI  - Anatomical education: a team effort.

PMID- 19598206
TI  - A review of current applications of mass spectrometry for neuroproteomics in
      epilepsy.
AB  - The brain is unquestionably the most fascinating organ, and the hippocampus is
      crucial in memory storage and retrieval and plays an important role in stress
      response. In temporal lobe epilepsy (TLE), the seizure origin typically involves
      the hippocampal formation. Despite tremendous progress, current knowledge falls
      short of being able to explain its function. An emerging approach toward an
      improved understanding of the complex molecular mechanisms that underlie
      functions of the brain and hippocampus is neuroproteomics. Mass spectrometry has
      been widely used to analyze biological samples, and has evolved into an
      indispensable tool for proteomics research. In this review, we present a general
      overview of the application of mass spectrometry in proteomics, summarize
      neuroproteomics and systems biology-based discovery of protein biomarkers for
      epilepsy, discuss the methodology needed to explore the epileptic hippocampus
      proteome, and also focus on applications of ingenuity pathway analysis (IPA) in
      disease research. This neuroproteomics survey presents a framework for large
      scale protein research in epilepsy that can be applied for immediate epileptic
      biomarker discovery and the far-reaching systems biology understanding of the
      protein regulatory networks. Ultimately, knowledge attained through
      neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the
      burden of epilepsy on society.

PMID- 19598208
TI  - The search for meaning-symptoms and transvaginal sonography screening for ovarian
      cancer: silent no more.

PMID- 19598207
TI  - Acetylation of cellulose nanowhiskers with vinyl acetate under moderate
      conditions.
AB  - A novel and straightforward method for the surface acetylation of cellulose
      nanowhiskers by transesterification of vinyl acetate is proposed. The reaction of
      vinyl acetate with the hydroxyl groups of cellulose nanowhiskers obtained from
      cotton linters was examined with potassium carbonate as catalyst. Results
      indicate that during the first stage of the reaction, only the surface of the
      nanowhiskers was modified, while their dimensions and crystallinity remained
      unchanged. With increasing reaction time, diffusion mechanisms controlled the
      rate, leading to nanowhiskers with higher levels of acetylation, smaller
      dimensions, and lower crystallinity. In THF, a solvent of low polarity, the
      suspensions from modified nanowhiskers showed improved stability with increased
      acetylation.

PMID- 19598209
TI  - Prenatal magnetic resonance imaging: towards optimized patient information.
AB  - OBJECTIVES: To investigate the perception of fetal magnetic resonance imaging
      (MRI) by women confronted with the necessity of a targeted prenatal examination
      because of suspicion of an abnormality, in order to develop a pre-scan
      information leaflet tailored to the information requirements of these women.
      METHODS: Sixty-two women were assessed by qualitative interview immediately
      before and after scanning. Data were analyzed by means of a qualitative content
      analysis. The transcribed interviews were coded within established categories,
      including knowledge of the purpose of the exam, understanding of the procedure,
      expectation of the baby's reaction, satisfaction with pre-information, experience
      of fetal MRI, distressing conditions during scanning, anxiety and suggestions for
      improvement of the scanning procedure. RESULTS: Pre-scan interviews indicated 66%
      of our sample to be well-informed about the purpose of fetal MRI. A realistic,
      detailed description of the examination was given by 37%. Only 32% expected the
      scanning to be safe for their baby. Despite the overall good tolerance of fetal
      MRI (63%), post-scan interviews revealed that 58% of women had experienced
      anxiety during MRI, which was partly due to the fearful perception of intensified
      fetal body movements during scanning. The quality of the pre-information leaflet
      was rated as sufficiently informative by 68% of the women. Suggestions for
      improvement were centered on physical conditions, the presence of the partner
      during scanning, and the availability of pre-scan briefings. CONCLUSIONS: Based
      on women's needs, detailed information about the fetal MRI procedure should be
      provided, containing clear-cut explanations about the purpose, course, method and
      possible distressing conditions. A leaflet describing these details should be
      given to women by the referring physician well in advance of the examination, and
      the woman given the opportunity to discuss unclear points.

PMID- 19598211
TI  - Does annual temperature influence the prevalence of otolaryngologic respiratory
      diseases?
AB  - OBJECTIVES/HYPOTHESIS: Determine if increasing annual temperature is associated
      with an increase in the prevalence of otolaryngologic respiratory diseases. STUDY
      DESIGN: Cross-sectional study. METHODS: Patients and disease variables were
      extracted from the National Health Interview Survey for the calendar years 1998
      to 2006 adult sample. Corresponding average annual temperature statistics were
      obtained from the National Climatic Data Center. The disease prevalences of hay
      fever, sinusitis, chronic bronchitis, and jaw/face pain (control group) were
      determined and tabulated according to mean annual temperature and compared
      graphically. Regression analysis for disease prevalence according to mean annual
      temperature was conducted. RESULTS: A total of 851,584 adults were sampled with a
      mean age of 35.7 years and a male:female ratio of 0.93:1. The overall disease
      prevalences for the disease conditions across all years of the study were (+/-95%
      confidence interval): hay fever (9.2% +/- 0.1%), sinusitis (15.0% +/- 0.2%),
      chronic bronchitis (4.5% +/- 0.1%) and pain in jaw/front of ear (4.5% +/- 0.1%).
      Regression analysis did not find a significant relationship between average
      annual temperature and the prevalence of disease for hay fever, jaw pain, or
      chronic bronchitis. A statistically significant but small regression coefficient
      (0.004) was noted for an increasing prevalence of sinusitis with increasing
      annual temperature (P = .031). CONCLUSIONS: Changes in mean annual temperature
      did not influence the prevalence of hay fever but did influence the prevalence of
      sinusitis over a 9-year period. Given the strong prevalence of hay fever and
      sinusitis, the effect of global warming on the otolaryngologic disease deserves
      continued epidemiologic surveillance.

PMID- 19598210
TI  - Alcohol consumption, finasteride, and prostate cancer risk: results from the
      Prostate Cancer Prevention Trial.
AB  - BACKGROUND: Current research is inconclusive regarding the relation between
      alcohol consumption and prostate cancer risk. In this study, the authors examined
      the associations of total alcohol, type of alcoholic beverage, and drinking
      pattern with the risk of total, low-grade, and high-grade prostate cancer.
      METHODS: Data for this study came from the 2129 participants in the Prostate
      Cancer Prevention Trial (PCPT) who had cancer detected during the 7-year trial
      and 8791 men who were determined by biopsy to be free of cancer at the trial end.
      Poisson regression was used to calculate relative risks (RRs) and 95% confidence
      intervals (95% CIs) for associations of alcohol intake with prostate cancer risk.
      RESULTS: Associations of drinking with high-grade disease did not differ by
      treatment arm. In combined arms, heavy alcohol consumption (> or =50 g of alcohol
      daily) and regular heavy drinking (> or =4 drinks daily on > or =5 days per week)
      were associated with increased risks of high-grade prostate cancer (RR, 2.01 [95%
      CI, 1.33-3.05] and 2.17 [95% CI, 1.42-3.30], respectively); less heavy drinking
      was not associated with risk. Associations of drinking with low-grade cancer
      differed by treatment arm. In the placebo arm, there was no association of
      drinking with risk of low-grade cancer. In the finasteride arm, drinking > or =50
      g of alcohol daily was associated with an increased risk of low-grade disease
      (RR, 1.89; 95% CI, 1.39-2.56); this finding was because of a 43% reduction in the
      risk of low-grade cancer attributable to finasteride treatment in men who drank
      <50 g of alcohol daily and the lack of an effect of finasteride in men who drank
      > or =50 g of alcohol daily (P(interaction) = .03). CONCLUSIONS: Heavy, daily
      drinking increased the risk of high-grade prostate cancer. Heavy drinking made
      finasteride ineffective for reducing prostate cancer risk.

PMID- 19598212
TI  - Electrogustometric assessment of taste after otologic surgery in children.
AB  - OBJECTIVES/HYPOTHESIS: Long term taste dysfunction after otologic surgery has
      never been characterized in children. The aim of this study is to determine the
      rates of gustatory dysfunction in normal and postotologic surgery in children.
      STUDY DESIGN: Cross-sectional study. METHODS: One hundred sixty children visiting
      a tertiary pediatric otolaryngology clinic, 4 to 18 years of age, were recruited.
      Surgical groups included patients who had undergone tympanoplasty, combined
      approach mastoidectomy, modified radical mastoidectomy, and unilateral and
      bilateral cochlear implantation. They were then tested using a Rion TR-06
      electrogustometer (Sensonics, Inc., Haddon Heights, NJ) using a standardized
      protocol to assess chorda tympani nerve function. An abnormal gustometry result
      was defined as any recording of > or =16 dB or a difference of 6 dB between ears.
      RESULTS: The control group had a 9% (5/61) abnormal electrogustometric threshold
      rate. Rates of dysfunction after surgery were: tympanoplasty (27%, 4/15),
      combined approach mastoidectomy (30%, 11/29), modified radical mastoidectomy
      (50%, 4/8). Unilateral cochlear implantation yielded a 26% (7/27) per ear risk of
      dysfunction, whereas bilateral cochlear implantation had a 5% (2/40) per ear
      risk. CONCLUSIONS: There is a 9% baseline level of electrogustometric abnormality
      in the pediatric population, which suggests a subclinical level of gustatory
      dysfunction. Normal electrogustometry was found in 50% of children after modified
      radical mastoidectomy, suggesting a degree of neural regenerative capacity.
      Finally, cochlear implantation, using newer surgical techniques (in the bilateral
      cochlear implant group) has a low risk for causing gustatory dysfunction,
      reducing concerns over the safety profile of bilateral cochlear implantation.

PMID- 19598214
TI  - Some statistics in bioinformatics: the fifth Armitage Lecture.
AB  - The spirit and content of the 2007 Armitage Lecture are presented in this paper.
      To begin, two areas of Peter Armitage's early work are distinguished: his
      pioneering research on sequential methods intended for use in medical trials and
      the comparison of survival curves. Their influence on much later work is
      highlighted, and motivate the proposal of several statistical 'truths' that are
      presented in the paper. The illustration of these truths demonstrates biology's
      new morphology and its dominance over statistics in this century. An overview of
      a recent proteomics ovarian cancer study is given as a warning of what can happen
      when bioinformatics meets epidemiology badly, in particular, when the study
      design is poor. A statistical bioinformatics success story is outlined, in which
      gene profiling is helping to identify novel genes and networks involved in mouse
      embryonic stem cell development. Some concluding thoughts are given.

PMID- 19598213
TI  - Parathyroid surgery and methylene blue: a review with guidelines for safe
      intraoperative use.
AB  - Methylene blue has been used to help facilitate parathyroid surgery for over 30
      years. Its use has been widely considered both safe and cost effective. Twenty
      six cases of a toxic metabolic encephalopathy, however, have been reported with
      its use. As a result, some surgeons have stopped using this technique altogether.
      It is now known that methylene blue is a monoamine oxidase inhibitor. When
      combined with drugs that increase central serotonin neurotransmission, serotonin
      toxicity results. This is the cause of the encephalopathy described in the
      literature. A case report, review of the literature, and guidelines as to its
      proper use are presented so as to allow for safe parathyroid surgery.

PMID- 19598215
TI  - Safe and rapid approach to the deviated nasal septum in children.

PMID- 19598216
TI  - Update on endoscopic management of lingual thyroglossal duct cysts.
AB  - OBJECTIVES/HYPOTHESIS: Thyroglossal duct cysts (TGDC) are uncommon congenital
      midline neck masses arising from tubal remnants of embryologic thyroid descent. A
      rare variant of TGDC can present in the central tongue base and is named lingual
      TGDC (LTGDC). Left untreated, LTGDC may present with life-threatening airway
      obstruction. TGDC require surgery for cure; however, the surgical approach to
      LTGDC has not been discussed fully. This study was designed to examine the
      incidence, clinical features, and surgical management of LTGDC. STUDY DESIGN:
      Retrospective chart review. METHODS: Retrospective chart review of patients from
      a pediatric tertiary care institution diagnosed with lingual TGDC from 1997 to
      2008. RESULTS: One hundred eighty-nine patients underwent surgical excision of
      TGDC, of which 16 (8.5%; mean age, 3 years) presented with lingual TGDC alone.
      Most lingual TGDC were discovered incidentally, although seven patients (44%)
      presented with moderate to severe upper airway obstruction. Endoscopic transoral
      excision was performed in each case. This included suspension laryngoscopy with
      electrocautery, electrocautery, and cold dissection, or a combination of
      microdebridement and electrocautery. Most patients were intubated electively
      overnight for airway protection. All patients recovered without complication and
      have shown no evidence of recurrence (median follow-up, 3.7 years). Two LTGDC
      cases were revisions of prior surgeries (marsupialization and an open procedure)
      performed at outside hospitals. CONCLUSIONS: Although rare, LTGDC frequently
      present as a prominent tongue base mass with the potential of life-threatening
      airway obstruction. Herein we described the typical presentation, workup, and
      ideal surgical approach of these lesions. Complete surgical extirpation can be
      performed successfully with endoscopic techniques and minimal risk of
      complication or recurrence.

PMID- 19598217
TI  - Molecular resonance vs. coblation tonsillectomy in children.
AB  - BACKGROUND: Quantum molecular resonance coagulation is an innovative technology
      that uses molecular resonance to cut and coagulate precisely, cleanly, and
      hemostatically at low tissue temperature levels. This technology offers a new
      possibility for tonsillectomy. OBJECTIVES: To compare molecular resonance (MRT)
      with coblation (CAT) devices for pediatric tonsillectomy. STUDY DESIGN:
      Prospective, two-group, randomized trial in a tertiary care pediatric
      institution. One hundred fifty-seven children for whom tonsillectomy was
      indicated were randomly assigned to receive MRT (n = 79) or CAT (n = 78). Main
      outcome measures included intraoperative time, blood loss, postoperative pain,
      and weight loss. Histopathologic examination was performed on all excised
      tonsils. Patients, parents, and pathologist were blinded to surgical modality.
      RESULTS: Histopathologic evaluation revealed significantly reduced thermal injury
      with MRT than with CAT (43 microns vs. 126, respectively, P < .001), and was
      statistically associated with reduced muscular, blood vessel, and nerve fiber
      damage. No intraoperative blood loss was observed in patients following MRT.
      Statistically significant reduced pain scores were related to the MRT (P < .002).
      In addition, the MRT method showed a quick return to normal diet with even weight
      gain during the 10-day postoperative period. One child in the CAT group
      experienced delayed bleeding and required readmission. CONCLUSIONS: Molecular
      resonance for pediatric tonsillectomy resulted in significantly reduced
      histopathologic thermal injury and lower pain scores compared with coblation.
      Further studies are advised to support these data.

PMID- 19598218
TI  - In reference to Impact of Second Primary Tumors on Survival in Head and Neck
      Cancer: An Analysis of 2,063 Cases.

PMID- 19598219
TI  - Successful treatment with daclizumab of refractory anaplastic lymphoma.
AB  - Anaplastic large cell lymphoma (ALCL) is a relatively rare and highly malignant
      form of non-Hodgkin lymphoma (NHL) which accounts for 10-15% of these childhood
      lymphomas. Current treatment protocols for ALCL in children consist of a short
      course of high intensity polychemotherapy. Here we describe an 8-year-old female
      with relapsed ALCL who achieved good response with anti-CD25 monoclonal antibody
      daclizumab. Daclizumab appears to offer a safe treatment option, but further
      research needs to be conducted in order to define its role in children with ALCL
      who do not respond to intensive chemotherapy.

PMID- 19598220
TI  - Racial differences in colorectal cancer survival in the Detroit Metropolitan
      Area.
AB  - BACKGROUND: Colorectal carcinoma is the second most common cause of cancer death
      with African Americans having lower survival compared with White Americans. The
      purpose of this study was to investigate the effect of demographics, clinical
      factors, and socioeconomic status (SES) on racial disparities in colorectal
      cancer survival in the Detroit Metropolitan Area. METHODS: The study population
      included 9078 individuals with primary invasive colorectal cancer identified
      between 1988 and 1992 through the Surveillance, Epidemiology, and End Results
      (SEER) program. Demographics, clinical information, and survival were obtained
      through SEER. SES was categorized using occupation, educational level, and
      poverty status at the census tract level. Kaplan-Meier survival curves and Cox
      proportional hazards regression were used to compare overall survival by race.
      RESULTS: African Americans were more likely to be diagnosed with stage IV disease
      (P < .001), and to reside within poor census tracts (P < .001) compared with
      White Americans. Unadjusted analysis showed that African Americans had a
      significantly higher risk of death compared with their White American
      counterparts (hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.07-1.20).
      After adjusting for age, marital status, sex, SES group, TNM stage, and
      treatment, race was no longer significantly associated with overall survival (HR,
      1.00; 95% CI, 0.92-1.09). Similar results were seen with colorectal cancer
      specific survival. CONCLUSIONS: Racial disparities in colorectal cancer survival
      dissipate after adjusting for other demographic and clinical factors. These
      results can potentially affect medical guidelines regarding screening and
      treatment, and possibly influence public health policies that can have a positive
      impact on equalizing racial differences in access to care.

PMID- 19598221
TI  - Increasing incidence of differentiated thyroid cancer in the United States, 1988
      2005.
AB  - BACKGROUND: Studies have reported an increasing incidence of thyroid cancer since
      1980. One possible explanation for this trend is increased detection through more
      widespread and aggressive use of ultrasound and image-guided biopsy. Increases
      resulting from increased detection are most likely to involve small primary
      tumors rather than larger tumors, which often present as palpable thyroid masses.
      The objective of the current study was to investigate the trends in increasing
      incidence of differentiated (papillary and follicular) thyroid cancer by size,
      age, race, and sex. METHODS: Cases of differentiated thyroid cancer (1988-2005)
      were analyzed using the National Cancer Institute's Surveillance Epidemiology and
      End Results (SEER) dataset. Trends in incidence rates of papillary and follicular
      cancer, race, age, sex, primary tumor size (<1.0 cm, 1.0-2.9 cm, 3.0-3.9 cm, and
      >4 cm), and SEER stage (localized, regional, distant) were analyzed using
      joinpoint regression and reported as the annual percentage change (APC). RESULTS:
      Incidence rates increased for all sizes of tumors. Among men and women of all
      ages, the highest rate of increase was for primary tumors <1.0 cm among men (1997
      2005: APC, 9.9) and women (1988-2005: APC, 8.6). Trends were similar between
      whites and blacks. Significant increases also were observed for tumors > or =4 cm
      among men (1988-2005: APC, 3.7) and women (1988-2005: APC, 5.70) and for distant
      SEER stage disease among men (APC, 3.7) and women (APC, 2.3). CONCLUSIONS: The
      incidence rates of differentiated thyroid cancers of all sizes increased between
      1988 and 2005 in both men and women. The increased incidence across all tumor
      sizes suggested that increased diagnostic scrutiny is not the sole explanation.
      Other explanations, including environmental influences and molecular pathways,
      should be investigated.

PMID- 19598222
TI  - Vigilance in ursine black and white colobus monkeys (Colobus vellerosus): an
      examination of the effects of conspecific threat and predation.
AB  - Vigilance is thought to have evolved as an antipredator defense but, in primates,
      conspecific threat often better explains this behavior. We examined vigilance in
      one group of Colobus vellerosus inhabiting the Boabeng-Fiema Monkey Sanctuary in
      Ghana. We aimed to (1) describe factors affecting vigilance in this population,
      and (2) examine the importance of predation avoidance and conspecific threat in
      explaining vigilance patterns. Because of a male takeover preceding the study,
      our focal group (B2) consisted of six adult males and three adult females. We
      collected 490 10-min focal samples (82 hr) from all adults in the group (N=9)
      from July to November, 2001. To avoid predators, individuals should be more
      vigilant (i) with fewer neighbors, and (ii) in areas of the canopy with higher
      predation risks. Conspecific threats can be divided into extra- and intra-group
      threats. Extra-group threats should lead to higher vigilance levels (iii) during
      intergroup encounters, and (iv) in areas where the home range overlaps with other
      groups of colobus. Intra-group threats should lead to greater vigilance (v) in
      the presence of neighbors and (vi) while feeding or occupying food patches (if
      resources are limiting). Our results best support the hypothesis that vigilance
      functions primarily to detect extra-group, conspecific threats. Individuals were
      most vigilant during intergroup encounters and in areas of range overlap, and
      monthly vigilance rates were associated with monthly encounter rates. Individuals
      tended to scan less in proximity to familiar vs. unfamiliar group mates,
      suggesting that relationship quality may affect colobus vigilance. Finally,
      predation pressures or anthropogenic disturbances might have influenced
      vigilance, as individuals were more vigilant low in the canopy. However, this
      last result could also be due to the lower visibility because of dense foliage or
      to the fact that the monkeys have access to fewer escape routes when ranging
      lower in the canopy.

PMID- 19598223
TI  - Effects of larval density on hematological stress indices in salamanders.
AB  - In animals with complex life cycles, the quality of juvenile environments is
      important in shaping the longer-term fitness of individuals. Larval density is a
      major factor governing quality of larval environments in amphibians, with high
      densities leading to reduced growth rates, smaller size at metamorphosis, and
      potentially long-lasting postmetamorphic effects. A little-studied effect of
      larval density is its impact on physiological stress of postmetamorphic
      individuals. We used a hematological approach, involving counts of specific white
      blood cells types (neutrophils and lymphocytes) that covary with corticosterone,
      to estimate stress levels in recently metamorphosed spotted salamanders
      (Ambystoma maculatum) that were reared in three different larval densities in
      outdoor mesocosms. In replicated treatments consisting of 12, 25, or 50 larvae,
      survival was, as expected, lowest and size at metamorphosis smallest in the
      highest density mesocosms. In addition, surviving salamanders from high-density
      treatments had significantly higher neutrophil to lymphocyte ratios, indicative
      of high levels of stress hormones (corticosterone). This trend was not a result
      of density-related differences in body condition as these did not vary with
      density. Further, estimated stress levels were similar regardless of whether the
      salamanders metamorphosed early or late, suggesting that the density effect on
      stress is long-lasting even once realized density has been reduced through
      mortality or early metamorphosis. These results may be important in understanding
      amphibian population dynamics, since research on other vertebrate taxa
      demonstrates that high hematological stress indicators lead to reduced growth,
      survival, and increased disease susceptibility in vertebrate animals.

PMID- 19598224
TI  - Accurate and precise determination of isotopic ratios by MC-ICP-MS: a review.
AB  - For many decades the accurate and precise determination of isotope ratios has
      remained a very strong interest to many researchers due to its important
      applications in earth, environmental, biological, archeological, and medical
      sciences. Traditionally, thermal ionization mass spectrometry (TIMS) has been the
      technique of choice for achieving the highest accuracy and precision. However,
      recent developments in multi-collector inductively coupled plasma mass
      spectrometry (MC-ICP-MS) have brought a new dimension to this field. In addition
      to its simple and robust sample introduction, high sample throughput, and high
      mass resolution, the flat-topped peaks generated by this technique provide for
      accurate and precise determination of isotope ratios with precision reaching
      0.001%, comparable to that achieved with TIMS. These features, in combination
      with the ability of the ICP source to ionize nearly all elements in the periodic
      table, have resulted in an increased use of MC-ICP-MS for such measurements in
      various sample matrices. To determine accurate and precise isotope ratios with MC
      ICP-MS, utmost care must be exercised during sample preparation, optimization of
      the instrument, and mass bias corrections. Unfortunately, there are
      inconsistencies and errors evident in many MC-ICP-MS publications, including
      errors in mass bias correction models. This review examines "state-of-the-art"
      methodologies presented in the literature for achievement of precise and accurate
      determinations of isotope ratios by MC-ICP-MS. Some general rules for such
      accurate and precise measurements are suggested, and calculations of combined
      uncertainty of the data using a few common mass bias correction models are
      outlined.

PMID- 19598226
TI  - The effect of the side chain length of Asp and Glu on coordination structure of
      Cu(2+) in a de novo designed protein.
AB  - Metal ions in proteins are important not only for the formation of the proper
      structures but also for various biological activities. For biological functions
      such as hydrolysis and oxidation, metal ions often adopt unusual coordination
      structures. We constructed a stable scaffold for metal binding to create
      distorted metal coordination structures. A stable four stranded alpha-helical
      coiled-coil structure was used as the scaffold, and the metal binding site was in
      the cavity created at the center of the structure. Two His residues and one Asp
      or Glu residue were used to coordinate the metal ions, AM2D and AM2E,
      respectively. Cu(2+) bound to AM2D with an equatorial planar coordination
      structure with two His, one Asp, and H(2)O as detected by electron spin resonance
      and UV spectral analyzes. On the other hand, Cu(2+) had a slightly distorted
      square planar structure when it bound two His and Glu in AM2E, due to the longer
      side-chain of the Glu residue as compared to the Asp residue. Computational
      analysis also supported the distorted coordination structure of Cu(2+) in AM2E.
      This construct should be useful to create various coordinations of metal ions for
      catalytic functions.

PMID- 19598227
TI  - A statistical thermodynamic approach for predicting the sequence-dependent
      nucleosome positioning along genomes.
AB  - Nucleosomes are the fundamental repeating unit of chromatin and constitute the
      structural building blocks of the eukaryotic genome. The distribution of
      nucleosomes along the genome is a significant aspect of chromatin structure and
      influences gene regulation through modulation of DNA accessibility. For this
      reason, an increasing interest is arising in models capable of predicting the
      nucleosome positioning along genomes. Toward this goal, we propose a theoretical
      model for predicting nucleosome thermodynamic stability in terms of DNA sequence.
      The model, based on a statistical mechanical approach allows the calculation of
      the canonical ensemble free energy involved in nucleosome formation. The
      theoretical free energies were evaluated for about one hundred nucleosome DNA
      tracts and successfully compared with those obtained in different laboratories
      with nucleosome competitive reconstitution (correlation coefficient equal to
      0.92). We extended these results to the nucleosome positioning along genomes. To
      test our model, the theoretical nucleosome distribution was compared with that of
      yeast genome experimentally determined. The results are comparable with those
      obtained by different authors adopting models based on identifying some recurrent
      sequence features obtained from the statistical analysis of a very large pool of
      nucleosomal DNA sequences provided by the positioning maps of genomes.

PMID- 19598228
TI  - Misinterpreted signals during guarantee volume ventilation in the newborn.

PMID- 19598229
TI  - The disease burden caused by pediatric pneumonia.

PMID- 19598230
TI  - Successful weaning of nitric oxide facilitated by a single dose of sildenafil in
      a baby with persistent pulmonary hypertension of the newborn.

PMID- 19598231
TI  - Influence of ventilatory settings on exhaled nitric oxide during high frequency
      oscillatory ventilation.
AB  - Nitric oxide (NO), which is produced in the lower airways, diffuses from cells
      into the air space and can be measured in exhaled air. The influence of high
      frequency oscillatory ventilation on the production of exhaled NO (eNO) has not
      been thoroughly studied. The objectives of this study are to establish an animal
      model for evaluation of lower airway NO and to evaluate settings in terms of
      frequency, mean airway pressure (MAP), amplitude pressure (amplitude), and
      inspiratory time ratio (t(I)/t(E)) during high frequency oscillatory ventilation
      on the production of eNO. An observational animal study was performed on 12
      female New Zealand White rabbits, which were anesthetized, tracheotomized and
      ventilated using a SensorMedics 3100A HFOV ventilator (SM3100A). The
      concentration of NO in exhaled gas was measured by chemiluminescence continuously
      from the nose and the side hole of the adaptor of endotracheal tube. The
      individual effects of the respiratory settings were evaluated. The results were
      analyzed by paired t-test or by the generalized estimating equation method. We
      found that the lower airway was the main source of the eNO, that amplitude, MAP,
      and t(I)/t(E) were positively correlated with the level of eNO and that frequency
      was negatively correlated with the level of eNO. These findings fit the stretch
      theory for the production of endogenous NO. Monitoring of eNO during HFOV may
      provide insights into lung mechanics and ventilation efficiency and be used in
      the future as a guide during clinical practice.

PMID- 19598232
TI  - Adenovirus infections within a family cohort in Iran.
AB  - BACKGROUND: Adenovirus is one of the most frequent viruses associated with acute
      respiratory infections (ARI). There is limited information of its transmission
      within the community. METHODS: Cohorts of 50 families with > or =two children
      were visited weekly for 2 months to ascertain the presence ARI in Rasht, Iran.
      Nasopharyngeal swabs were obtained from symptomatic participants and at 3-4-day
      intervals to assess the duration of adenovirus shedding. Adenoviruses were
      identified by PCR and adenovirus positive amplicons were subjected to DNA
      sequencing. RESULTS: Thirty-three (35%) of 94 ARI episodes in children and 8
      (27%) of 30 episodes in adults were due to adenovirus (not significant, NS).
      25/50 (50%) families had adenovirus infections. Children had more infections than
      adults, were more likely to develop symptoms if there was a symptomatic case
      within the household and episodes had a longer duration (P < 0.05). Adenoviruses
      were recovered for a median of 11 (interquartile range 5-26) days of follow up in
      children and 7 (2-20) days in adults (NS). Adenovirus-7 was the most frequent
      serotype (12 families), followed by adenovirus-6 (5 families), adenovirus-1 and 2
      (4 families each), and adenovirus-5 (3 families). Both adenovirus-5 and 7
      amplicons fell into two clusters. No mutations were observed during transmission
      within a family. CONCLUSION: A substantial proportion of ARI in the community are
      due to adenovirus with further transmission within the family. Children > or =2
      years experienced a higher proportion of infections than younger children and
      adults. Viral shedding was more prolonged in children and adenovirus-7 and 5
      predominated with several clusters co-circulating in the same season.

PMID- 19598233
TI  - Native like structure in the unfolded state of the villin headpiece helical
      subdomain, an ultrafast folding protein.
AB  - The villin headpiece subdomain, HP36, is the smallest naturally occurring protein
      that folds cooperatively. Its small size, rapid folding, and simple three-helix
      topology have made it an extremely popular system for computational studies of
      protein folding. The role of unfolded state structure in rapid folding is an area
      of active investigation, but relatively little is known about the properties of
      unfolded states under native conditions. A peptide fragment, HP21, which contains
      the first and second helices of HP36 has been shown to be a good model for
      structure in the unfolded state of the intact domain but a detailed description
      of the conformational propensities of HP21 is lacking and the balance between
      native and nonnative interactions is not known. A series of three-dimensional NMR
      experiments were performed on (13)C, (15)N-labeled HP21 to investigate in detail
      its conformational propensities. Analysis of (13)C(alpha), (13)C(beta), (13)CO
      chemical shifts, Deltadelta(13)C(alpha) - Deltadelta(13)C(beta) secondary shifts,
      the secondary structure propensity scores, NOEs, (15)N R(2) values and comparison
      of experimental chemical shifts with those of HP36 and with chemical shifts
      calculated using the SHIFTS and SHIFTX programs all indicate that there is
      significant native like structure in the HP21 ensemble, and thus by implication
      in the unfolded state of HP36.

PMID- 19598234
TI  - Conformational changes in redox pairs of protein structures.
AB  - Disulfides are conventionally viewed as structurally stabilizing elements in
      proteins but emerging evidence suggests two disulfide subproteomes exist. One
      group mediates the well known role of structural stabilization. A second redox
      active group are best known for their catalytic functions but are increasingly
      being recognized for their roles in regulation of protein function. Redox-active
      disulfides are, by their very nature, more susceptible to reduction than
      structural disulfides; and conversely, the Cys pairs that form them are more
      susceptible to oxidation. In this study, we searched for potentially redox-active
      Cys Pairs by scanning the Protein Data Bank for structures of proteins in
      alternate redox states. The PDB contains over 1134 unique redox pairs of
      proteins, many of which exhibit conformational differences between alternate
      redox states. Several classes of structural changes were observed, proteins that
      exhibit: disulfide oxidation following expulsion of metals such as zinc; major
      reorganisation of the polypeptide backbone in association with disulfide redox
      activity; order/disorder transitions; and changes in quaternary structure. Based
      on evidence gathered supporting disulfide redox activity, we propose disulfides
      present in alternate redox states are likely to have physiologically relevant
      redox activity.

PMID- 19598235
TI  - Genes related to sex steroids, neural growth, and social-emotional behavior are
      associated with autistic traits, empathy, and Asperger syndrome.
AB  - Genetic studies of autism spectrum conditions (ASC) have mostly focused on the
      "low functioning" severe clinical subgroup, treating it as a rare disorder.
      However, ASC is now thought to be relatively common ( approximately 1%), and
      representing one end of a quasi-normal distribution of autistic traits in the
      general population. Here we report a study of common genetic variation in
      candidate genes associated with autistic traits and Asperger syndrome (AS). We
      tested single nucleotide polymorphisms in 68 candidate genes in three functional
      groups (sex steroid synthesis/transport, neural connectivity, and social
      emotional responsivity) in two experiments. These were (a) an association study
      of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum
      Quotient (AQ)) in a population sample (n=349); and (b) a case-control association
      study on a sample of people with AS, a "high-functioning" subgroup of ASC
      (n=174). 27 genes showed a nominally significant association with autistic traits
      and/or ASC diagnosis. Of these, 19 genes showed nominally significant association
      with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the
      neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio
      responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes
      showed nominally significant association with AS. In the sex steroid group, this
      included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this
      included OXT. Six genes were nominally associated in both experiments, providing
      a partial replication. Eleven genes survived family wise error rate (FWER)
      correction using permutations across both experiments, which is greater than
      would be expected by chance. CYP11B1 and NTRK1 emerged as significantly
      associated genes in both experiments, after FWER correction (P<0.05). This is the
      first candidate-gene association study of AS and of autistic traits. The most
      promising candidate genes require independent replication and fine mapping.

PMID- 19598237
TI  - Mutagen structure and transcriptional response: induction of distinct
      transcriptional profiles in Salmonella TA100 by the drinking-water mutagen MX and
      its homologues.
AB  - The relationship between chemical structure and biological activity has been
      examined for various compounds and endpoints for decades. To explore this
      question relative to global gene expression, we performed microarray analysis of
      Salmonella TA100 after treatment under conditions of mutagenesis by the drinking
      water mutagen MX and two of its structural homologues, BA-1, and BA-4.
      Approximately 50% of the genes expressed differentially following MX treatment
      were unique to MX; the corresponding percentages for BA-1 and BA-4 were 91 and
      80, respectively. Among these mutagens, there was no overlap of altered Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways or RegulonDB regulons. Among
      the 25 Comprehensive Microbial Resource functions altered by these mutagens, only
      four were altered by more than one mutagen. Thus, the three structural homologues
      produced distinctly different transcriptional profiles, with none having a single
      altered KEGG pathway in common. We tested whether structural similarity between a
      xenobiotic and endogenous metabolites could explain transcriptional changes. For
      the 830 intracellular metabolites in Salmonella that we examined, BA-1 had a high
      degree of structural similarity to 2-isopropylmaleate, which is the substrate for
      isopropylmalate isomerase. The transcription of the gene for this enzyme was
      suppressed twofold in BA-1-treated cells. Finally, the distinct transcriptional
      responses of the three structural homologues were not predicted by a set of
      phenotypic anchors, including mutagenic potency, cytotoxicity, mutation spectra,
      and physicochemical properties. Ultimately, explanations for varying
      transcriptional responses induced by compounds with similar structures await an
      improved understanding of the interactions between small molecules and the
      cellular machinery.

PMID- 19598238
TI  - Watson's analytical approach for immunofluorescence histogram analysis.
AB  - In this short note, the key points of the histogram analysis method proposed by
      Watson (Cytometry 2001;43:55-68) were examined. The complete relationship among
      the mean values of the distributions on which that method is based was derived
      analytically. It was shown that the symmetry assumption is not necessary, and
      that the assumption of equal variances of the unlabeled and labeled cell
      distributions cannot be verified a posteriori. Moreover, a possible shift between
      the unlabeled cell distribution in the test and the negative control may greatly
      influence the estimation of the labeled cell percentage. Finally, by using an
      experimental set of histograms, it was shown that the assumptions underlying
      Watson's analytical method are likely not to be fulfilled in real
      immunofluorescence data.

PMID- 19598239
TI  - QASI, an international quality management system for CD4 T-cell enumeration
      focused to make a global difference.
AB  - BACKGROUND: A significant worldwide mobilization effort to treat people with HIV
      disease began in 2003. Most guidelines for initiating antiretroviral therapy
      require reliable and reproducible CD4 T-cell counting. Therefore, any effort that
      improves global availability of quality managed assessment schemes for CD4 T-cell
      enumeration is a positive achievement for the clinical management of AIDS on a
      worldwide scale. METHODS: The Canadian QASI-Quality Management System (QMS) has
      been in operation for over a decade. More recently, QMS has fine-tuned its
      strategy to optimize its global impact in the fight against the HIV/AIDS
      pandemic. Three modifications were implemented: (1) introduction of skills and
      knowledge transfer workshops pertaining to the initiation of national quality
      management programs for CD4 counting, (2) introduction of a road map to establish
      domestic EQAP for countries that are ready, and (3) introduction of a statistical
      analysis package which permits continuous monitoring of global impact of the QASI
      QMS. RESULTS: Based on QASI-QMS distribution of specimens over four consecutive
      participation cycles, there was decreased interlaboratory variation for both low
      and medium CD4 T-cell levels. After three cycles of consecutive participation,
      there is an average of 38 and 26% error reduction reported for the mid and low
      CD4 levels, respectively. CONCLUSION: The program improvements mentioned earlier
      appear to have had a profound effect with regard to enhancing the performance of
      laboratories participating in the QASI-QMS. Specifically, there is a significant
      reduction in interlaboratory variability of CD4 T-cell counts resulting from
      continuous participation in the QASI-QMS.

PMID- 19598236
TI  - The heel and toe of the cell's foot: a multifaceted approach for understanding
      the structure and dynamics of focal adhesions.
AB  - Focal adhesions (FAs) are large clusters of transmembrane receptors of the
      integrin family and a multitude of associated cytoplasmic "plaque" proteins,
      which connect the extracellular matrix-bound receptors with the actin
      cytoskeleton. The formation of nearly stationary FAs defines a boundary between
      the dense and highly dynamic actin network in lamellipodium and the sparser and
      more diverse cytoskeletal organization in the lamella proper, creating a template
      for the organization of the entire actin network. The major "mechanical" and
      "sensory" functions of FAs; namely, the nucleation and regulation of the
      contractile, myosin-II-containing stress fibers and the mechanosensing of
      external surfaces depend, to a major extent, on the dynamics of molecular
      components within FAs. A central element in FA regulation concerns the positive
      feedback loop, based on the most intriguing feature of FAs; that is, their
      dependence on mechanical tension developing by the growing stress fibers. FAs
      grow in response to such tension, and rapidly disassemble upon its relaxation. In
      this article, we address the mechanistic relationships between the process of FA
      development, maturation and dissociation and the dynamic molecular events, which
      take place in different regions of the FA, primarily in the distal end of this
      structure (the "toe") and the proximal "heel," and discuss the central role of
      local mechanical forces in orchestrating the complex interplay between FAs and
      the actin system.

PMID- 19598240
TI  - Initial findings on visual acuity thresholds in an African elephant (Loxodonta
      africana).
AB  - There are only a few published examinations of elephant visual acuity. All
      involved Asian elephants (Elephas maximus) and found visual acuity to be between
      8' and 11' of arc for a stimulus near the tip of the trunk, equivalent to a 0.50
      cm gap, at a distance of about 2 m from the eyes. We predicted that African
      elephants (Loxodonta africana) would have similarly high visual acuity, necessary
      to facilitate eye-trunk coordination for feeding, drinking and social
      interactions. When tested on a discrimination task using Landolt-C stimuli, one
      African elephant cow demonstrated a visual acuity of 48' of arc. This represents
      the ability to discriminate a gap as small as 2.75 cm in a stimulus 196 cm from
      the eye. This single-subject study provides a preliminary estimate of the visual
      acuity of African elephants.

PMID- 19598241
TI  - Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and
      spine morphology in central nervous system neurons.
AB  - Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting
      of brain-derived neurotrophic factor (BDNF) to the regulated pathway for activity
      dependent secretion from CNS neurons. CPE knockout (CPE-KO) mice have many
      neurological deficits, including deficits in learning and memory. Here, we
      analyzed the dendritic arborization and spine morphology of CPE-KO mice to
      determine a possible correlation of defects in such structures with the
      neurological deficits observed in these animals. Analysis of pyramidal neurons in
      layer V of cerebral cortex and in hippocampal CA1 region in 14-week-old CPE-KO
      mice showed more dendritic complexity compared with wild type (WT) mice. There
      were more dendritic intersections and more branch points in CPE-KO vs. WT
      neurons. Comparison of pyramidal cortical neurons in 6- vs. 14-week-old WT mice
      showed a decrease in dendritic arborization, reflecting the occurrence of normal
      dendritic pruning. However, this did not occur in CPE-KO neurons. Furthermore,
      analysis of spine morphology demonstrated a significant increase in the number of
      D-type spines regarded as nonfunctional in the cortical neurons of CPE-KO
      animals. Our findings suggest that CPE is an important, novel player in mediating
      appropriate dendritic patterning and spine formation in CNS neurons.

PMID- 19598242
TI  - Leukemia inhibitory factor regulates the timing of oligodendrocyte development
      and myelination in the postnatal optic nerve.
AB  - Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes both
      in vitro and in an animal model of multiple sclerosis, but the possible role of
      LIF signaling in myelination during normal development has not been investigated.
      We find that LIF(-/-) mice have a pronounced myelination defect in optic nerve at
      postnatal day 10. Myelin basic protein (MBP)- and proteolipid protein (PLP)
      positive myelin was evident throughout the optic nerve in the wild-type mice, but
      staining was present only at the chiasmal region in LIF(-/-) mice of the same
      age. Further experiments suggest that the myelination defect was a consequence of
      a delay in maturation of oligodendrocyte precursor cell (OPC) population. The
      number of Olig2-positive cells was dramatically decreased in optic nerve of LIF(
      /-) mice, and the distribution of Olig2-positive cells was restricted to the
      chiasmal region of the nerve in a steep gradient toward the retina. Gene
      expression profiling and cell culture experiments revealed that OPCs from P10
      optic nerve of LIF(-/-) mice remained in a highly proliferative immature stage
      compared with littermate controls. Interestingly, by postnatal day 14, MBP
      immunostaining in the LIF(-/-) optic nerve was comparable to that of LIF(+/+)
      mice. These results suggest that, during normal development of mouse optic nerve,
      there is a defined developmental time window when LIF is required for correct
      myelination. Myelination seems to recover by postnatal day 14, so LIF is not
      necessary for the completion of myelination during postnatal development.

PMID- 19598244
TI  - Effect of tannic acid on iron absorption in straw-colored fruit bats (Eidolon
      helvum).
AB  - Excessive absorption and subsequent storage of dietary iron has been found in a
      variety of captively held birds and mammals, including fruit bats. It is thought
      that feeding a diet that is low in iron can prevent the onset of this disease;
      however, manufacturing a diet with commonly available foodstuffs that contains a
      sufficiently low iron concentration is difficult. An alternative is to feed
      captive animals that may be susceptible to this disease potential iron chelators
      such as tannins that may bind to iron and block its absorption. Using stable
      isotope methods established in humans, we measured iron bioavailability in straw
      colored fruit bats (Eidolon helvum) and tested whether tannic acid significantly
      reduced the extent of iron absorption. Regardless of dose, tannic acid
      significantly reduced iron absorption (by 40%) and in the absence of tannic acid,
      iron absorption was extensive in this species (up to 30%), more so than in
      humans. Species susceptible to iron storage disease may efficiently absorb iron
      in the gut regardless of iron status, and supplementing these species with tannic
      acid in captivity may provide an alternative or additional means of preventing
      the development of this disease.

PMID- 19598243
TI  - O-linked beta-N-acetylglucosaminylation in mouse embryonic neural precursor
      cells.
AB  - In neural stem cells (NSCs), glycoconjugates and carbohydrate antigens are known
      not only to serve as excellent cell surface biomarkers for cellular
      differentiation and development but also to play important functional roles in
      determining cell fate. O-linked beta-N-acetylglucosamine (O-GlcNAc), which
      modifies nuclear and cytoplasmic proteins on the serine and threonine residues,
      is also expected to play an important regulatory role. It is not known, however,
      whether O-GlcNAc is expressed in NSCs or what the function of this expression is.
      In this study, we evaluated the patterns and possible functions of O
      GlcNAcylation in mouse embryonic neuroepithelial cells (NECs), which are known to
      be rich in NSCs. We confirmed the expression of O-GlcNAc transferase, O
      GlcNAcase, and several O-GlcNAcylated proteins in NECs. Treatment of NECs with O
      GlcNAcase inhibitors, PUGNAc and streptozotocin, induced robust accumulation of O
      GlcNAc in NECs and reduction of number of NECs. In O-GlcNAcase inhibitor-treated
      NECs, the Ras-mitogen-activated protein kinase pathway and the
      phosphatidylinositol 3-kinase-Akt pathway, important for proliferation and
      survival, respectively, were intact, but caspase-3, an executioner for cell
      death, was activated. These results suggest the possibility that O-GlcNAc is
      involved in cell death signaling in NECs. Furthermore, in NECs, we identified an
      O-GlcNAc-modified protein, Sp1 transcription factor. Our study is the first to
      evaluate expression and functions of O-GlcNAc in NECs.

PMID- 19598245
TI  - Involvement of GATA transcription factors in the regulation of endogenous bovine
      interferon-tau gene transcription.
AB  - Expression of interferon-tau (IFNT), necessary for pregnancy establishment in
      ruminant ungulates, is regulated in a temporal and spatial manner. However,
      molecular mechanisms by which IFNT gene transcription is regulated in this manner
      have not been firmly established. In this study, DNA microarray/RT-PCR analysis
      between bovine trophoblast CT-1 and Mardin-Darby bovine kidney (MDBK) cells was
      initially performed, finding that transcription factors GATA2, GATA3, and GATA6
      mRNAs were specific to CT-1 cells. These mRNAs were also found in Days 17, 20,
      and 22 (Day 0 = day of estrus) bovine conceptuses. In examining other bovine cell
      lines, ovary cumulus granulosa (oCG) and ear fibroblast (EF) cells, GATA2 and
      GATA3, but not GATA6, were found specific to the bovine trophoblast cells. In
      transient transfection analyses using the upstream region (-631 to +59 bp) of
      bovine IFNT gene (bIFNT, IFN-tau-c1), over-expression of GATA2/GATA3 did not
      affect the transcription of bIFNT-reporter construct in human choriocarcinoma
      JEG3 cells. Transfection of GATA2, GATA3, ETS2, and/or CDX2, however, was
      effective in the up-regulation of the bIFNT construct transfected into bovine oCG
      and EF cells. One Point mutation studies revealed that among six potential GATA
      binding sites located on the upstream region of the bIFNT gene, the one next to
      ETS2 site exhibited reduced luciferase activity. In CT-1 cells, endogenous bIFNT
      gene transcription was up-regulated by over-expression of GATA2 or GATA3, but
      down-regulated by siRNA specific to GATA2 mRNA. These data suggest that GATA2/3
      is involved in trophoblast-specific regulation of bIFNT gene transcription.

PMID- 19598246
TI  - Notch-Hes1 pathway contributes to the cochlear prosensory formation potentially
      through the transcriptional down-regulation of p27Kip1.
AB  - The Notch signaling pathway has a crucial role in the differentiation of hair
      cells and supporting cells by mediating "lateral inhibition" via the ligands
      Delta-like1 (Dll1) and Jagged2 (Jag2) and the effectors Hes1 and Hes5 during
      mammalian inner ear development. Recently, another Notch ligand, Jagged1 (Jag1)
      dependent Notch activation, has been revealed to be important for the
      determination of the prosensory region in the earlier stage before cell
      differentiation. However, little is known about the effectors of the Notch
      pathway in this context. P27(Kip1), a cyclin-dependent kinase inhibitor, is also
      known to demarcate the prosensory region in the cochlear primordium, which
      consists of the sensory progenitors that have completed their terminal mitoses.
      Hes1 reportedly promotes precursor cell proliferation through the transcriptional
      down-regulation of p27(Kip1) in the thymus, liver, and brain. In this study, we
      observed Hes1 as a mediator between the Notch signaling pathway and the
      regulation of proliferation of sensory precursor cells by p27(Kip1) in the
      developing cochlea. We showed that Hes1, but not Hes5, was weakly expressed at
      the time of onset of p27(Kip1). The expression pattern of Hes1 prior to cell
      differentiation was similar to that of activated Notch1. P27(Kip1) was up
      regulated and BrdU-positive S-phase cells were reduced in the developing cochlear
      epithelium of Hes1 null mice. These results suggest that the Notch-Hes1 pathway
      may contribute to the adequate proliferation of sensory precursor cells via the
      potential transcriptional down-regulation of p27(Kip1) expression and play a
      pivotal role in the correct prosensory determination.

PMID- 19598248
TI  - Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence
      in mice.
AB  - Microsomal epoxide hydrolase (mEH) and cytochrome P-450 (CYP) ensure the rapid
      detoxification of epoxides generated during the oxidative metabolism of
      xenobiotics. Although CYP has been demonstrated to modulate methamphetamine
      (METH)-induced behavioral effects, little is known about the role of the mEH gene
      on these effects. We examined the role of mEH gene expression in METH-induced
      conditioned place preference and behavioral sensitization by using mEH(-/-) and
      wild-type (WT) mice. Extracellular dopamine (DA) levels and DA uptake into
      synaptosomes were assessed by using an in vivo microdialysis and [(3)H]DA uptake
      assay. We applied double-label immunocytochemistry to characterize mEH-positive
      cellular types. METH-induced behavioral responses paralleled striatal c-Fos-like
      immunoreactivity. METH treatment resulted in increased extracellular DA levels in
      the nucleus accumbens but decreased synaptosomal DA uptake in the striatum. These
      behavioral and neurochemical changes were more pronounced in the mEH(-/-) mice
      than in WT mice. In WT mice, mEH-like immunoreactivity was expressed in
      astrocytes labeled by GFAP or S100B after METH treatment. The results suggest
      that epoxide intermediates mediate METH drug dependence and that astrocytic
      reactions of mEH protein are important in the endogenous modulation in response
      to METH drug dependence.

PMID- 19598247
TI  - Expression of alpha5 integrin rescues fibronectin responsiveness in NT2N CNS
      neuronal cells.
AB  - The extracellular matrix protein fibronectin is implicated in neuronal
      regeneration in the peripheral nervous system. In the central nervous system
      (CNS), fibronectin is up-regulated at sites of penetrating injuries and stroke;
      however, CNS neurons down-regulate the fibronectin receptor alpha5beta1 integrin
      during differentiation and generally respond poorly to fibronectin. NT2N CNS
      neuron-like cells (derived from NT2 precursor cells) have been used in
      preclinical and clinical studies for treatment of stroke and a variety of CNS
      injury and disease models. Here we show that, like primary CNS neurons, NT2N
      cells down-regulate alpha5beta1 integrin during differentiation and respond
      poorly to fibronectin. The poor neurite outgrowth by NT2N cells on fibronectin
      can be rescued by transducing NT2 precursors with a retroviral vector expressing
      alpha5 integrin under the control of the murine stem cell virus 5' long terminal
      repeat. Sustained alpha5 integrin expression is compatible with the CNS-like
      neuronal differentiation of NT2N cells and does not prevent robust neurite
      outgrowth on other integrin ligands. Thus, alpha5 integrin expression in CNS
      neuronal precursor cells may provide a strategy for enhancing the outgrowth and
      survival of implanted cells in cell-replacement therapies for CNS injury and
      disease.

PMID- 19598249
TI  - Inactivation of fibroblast growth factor receptor signaling in myelinating glial
      cells results in significant loss of adult spiral ganglion neurons accompanied by
      age-related hearing impairment.
AB  - Hearing loss has been attributed to many factors, including degeneration of
      sensory neurons in the auditory pathway and demyelination along the cochlear
      nerve. Fibroblast growth factors (FGFs), which signal through four receptors
      (Fgfrs), are produced by auditory neurons and play a key role in embryonic
      development of the cochlea and in neuroprotection against sound-induced injury.
      However, the role of FGF signaling in the maintenance of normal auditory function
      in adult and aging mice remains to be elucidated. Furthermore, the contribution
      of glial cells, which myelinate the cochlear nerves, is poorly understood. To
      address these questions, we generated transgenic mice in which Fgfr1 and Fgfr2
      were specifically inactivated in Schwann cells and oligodendrocytes but not in
      neurons. Adult mutant mice exhibited late onset of hearing impairment, which
      progressed markedly with age. The hearing impairment was accompanied by
      significant loss of myelinated spiral ganglion neurons. The pathology extended
      into the cochlear nucleus, without apparent loss of myelin or of the deletion
      bearing glial cells themselves. This suggests that perturbation of FGF receptor
      mediated glial function leads to the attenuation of glial support of neurons,
      leading to their loss and impairment of auditory functions. Thus, FGF/FGF
      receptor signaling provides a potentially novel mechanism of maintaining
      reciprocal interactions between neurons and glia in adult and aging animals.
      Dysfunction of glial cells and FGF receptor signaling may therefore be implicated
      in neurodegenerative hearing loss associated with normal aging.

PMID- 19598250
TI  - Tissue kallikrein alleviates glutamate-induced neurotoxicity by activating ERK1.
AB  - Glutamate-induced neurotoxicity consequent to N-methyl-D-aspartic acid (NMDA) and
      2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propionic acid (AMPA) receptor
      activation underlies the pathogenesis of a wide range of central nervous system
      disorders, including brain ischemia. Prevention of ischemia/reperfusion (I/R)
      induced neuronal injury has long been regarded as an effective therapeutic
      strategy for ischemia. Human tissue kallikrein (TK) gene transfer has been shown
      to protect neurons against cerebral I/R-induced apoptosis and oxidative stress,
      via activation of the brandykinin B2 receptor (B2R). However, little is known
      about the role of TK on glutamate-induced neurotoxicity. Here we report that
      pretreatment of cultured cortical neurons with TK largely prevented glutamate
      induced morphological changes and cell death. We found that TK pretreatment
      alleviated glutamate-induced oxidative stress by inhibiting neuronal nitric oxide
      synthase (nNOS) activity, thereby reducing the generation of nitric oxide (NO)
      and reactive oxygen species (ROS). Blockage of NMDA and AMPA receptors by their
      specific antagonists MK801 and CNQX had effects similar to those of TK
      administration. Furthermore, we found that the extracellular signal-regulated
      kinase 1/2 cascade (ERK1/2), particularly ERK1, and nuclear factor-kappaB (NF
      kappaB) were involved in TK neuroprotection against glutamate-induced
      neurotoxicity. TK pretreatment activated ERK1 and NF-kappaB, leading to enhanced
      expression of brain-derived neurotrophic factor (BDNF) mRNA and antiapoptotic
      gene Bcl-2 protein. Collectively, these findings demonstrate that TK attenuates
      glutamate-induced apoptosis through an intracellular signaling pathway including
      activation of B2R, ERK1/2, and NF-kappaB and up-regulation of BDNF and Bcl-2
      expression. Thus, TK represents a promising therapeutic strategy for ischemic
      stroke.

PMID- 19598251
TI  - Apoptosis and autophagy in rat cerebellar granule neuron death: Role of reactive
      oxygen species.
AB  - Programmed cell death (PCD) has been defined as an active, controlled process in
      which cells participate in their own demise. Apoptosis, or type I PCD, has been
      widely characterized, both morphologically and biochemically. More recently,
      autophagy, the self-digesting mechanism involved in the removal of cytoplasmic
      long-lived proteins, has been involved in cell death, and type II PCD is defined
      as cell death occurring with autophagic features. Neurons can undergo more than
      one type of PCD as a backup mechanism when the traditional death pathway is
      inhibited or in response to a particular death-inducing stimulus. Reactive oxygen
      species (ROS) have been shown to be important signaling molecules in the
      execution of apoptosis and, more recently, in the autophagic pathway. In this
      work, we characterize apoptotic and autophagic cell death in rat cerebellar
      granule neuron (CGN) culture, a widespread model for the study of neuronal death.
      Potassium deprivation (K5) and staurosporine (STS) were used for death induction.
      We found apoptotic and autophagic features under both conditions. Caspase
      inhibition as well as autophagy inhibition by 3-methyl adenine decreased cell
      death. Moreover, CGN can undergo the alternative type of cell death when the
      other one is inhibited. An antioxidant or NADPH oxidase inhibitors delayed
      apoptosis and had no effect in autophagic features. Thus, we found that autophagy
      plays a role in cell death of CGN and that, when cells are treated with K5 or
      STS, both autophagy and ROS seem to promote apoptosis by independent mechanisms.

PMID- 19598252
TI  - Atrophy and neuron loss: effects of a protein-deficient diet on sympathetic
      neurons.
AB  - Protein deficiency is one of the biggest public health problems in the world,
      accounting for about 30-40% of hospital admissions in developing countries.
      Nutritional deficiencies lead to alterations in the peripheral nervous system and
      in the digestive system. Most studies have focused on the effects of protein
      deficient diets on the enteric neurons, but not on sympathetic ganglia, which
      supply extrinsic sympathetic input to the digestive system. Hence, in this study,
      we investigated whether a protein-restricted diet would affect the quantitative
      structure of rat coeliac ganglion neurons. Five male Wistar rats (undernourished
      group) were given a pre- and postnatal hypoproteinic diet receiving 5% casein,
      whereas the nourished group (n = 5) was fed with 20% casein (normoproteinic
      diet). Blood tests were carried out on the animals, e.g., glucose, leptin, and
      triglyceride plasma concentrations. The main structural findings in this study
      were that a protein-deficient diet (5% casein) caused coeliac ganglion (78%) and
      coeliac ganglion neurons (24%) to atrophy and led to neuron loss (63%).
      Therefore, the fall in the total number of coeliac ganglion neurons in protein
      restricted rats contrasts strongly with no neuron losses previously described for
      the enteric neurons of animals subjected to similar protein-restriction diets.
      Discrepancies between our figures and the data for enteric neurons (using very
      similar protein-restriction protocols) may be attributable to the counting method
      used. In light of this, further systematic investigations comparing 2-D and 3-D
      quantitative methods are warranted to provide even more advanced data on the
      effects that a protein-deficient diet may exert on sympathetic neurons. (c) 2009
      Wiley-Liss, Inc.

PMID- 19598254
TI  - Insulin adsorption into porous charged membranes: effect of the electrostatic
      interaction.
AB  - Insulin adsorption into a series of porous charged membranes was investigated by
      batch adsorption experiments, and the experimental results were analyzed by the
      homogeneous diffusion model. The membranes used in this study were prepared by
      pore-surface modification of porous poly(acrylonitrile) (PAN) membranes by
      grafting with weak acidic and basic functional groups. The amount of insulin
      adsorbed into the membrane was determined from the material balance of insulin.
      The insulin partition coefficient K between the membrane and solution was
      estimated from the equilibrium adsorption amount, and the effective diffusion
      coefficient D was estimated by matching the model with the experimental data as a
      fitting parameter. The dependence of K and D on the charge properties of the
      insulin and membrane is observed and discussed. The partition coefficient K
      increased when the insulin and the membrane carried opposite charges, on the
      other hand, the effective diffusion coefficient D was reduced. These results
      indicate that the electrostatic interaction between the insulin and the membranes
      played an important role in the insulin adsorption.

PMID- 19598253
TI  - Feeding live prey to zoo animals: response of zoo visitors in Switzerland.
AB  - In summer 2007, with the help of a written questionnaire, the attitudes of more
      than 400 visitors to the zoological garden of Zurich, Switzerland, toward the
      idea of feeding live insects to lizards, live fish to otters, and live rabbits to
      tigers were investigated. The majority of Swiss zoo visitors agreed with the idea
      of feeding live prey (invertebrates and vertebrates) to zoo animals, both off-
      and on-exhibit, except in the case of feeding live rabbits to tigers on-exhibit.
      Women and frequent visitors of the zoo disagreed more often with the on-exhibit
      feeding of live rabbits to tigers. Study participants with a higher level of
      education were more likely to agree with the idea of feeding live invertebrates
      and vertebrates to zoo animals off-exhibit. In comparison to an earlier study
      undertaken in Scotland, zoo visitors in Switzerland were more often in favor of
      the live feeding of vertebrates. Feeding live prey can counter the loss of
      hunting skills of carnivores and improve the animals' well-being. However,
      feeding enrichments have to strike a balance between optimal living conditions of
      animals and the quality of visitor experience. Our results show that such a
      balance can be found, especially when live feeding of mammals is carried out off
      exhibit. A good interpretation of food enrichment might help zoos to win more
      support for the issue, and for re-introduction programs and conservation.

PMID- 19598258
TI  - Heat-shock pretreatment inhibits sorbitol-induced apoptosis in K562, U937 and
      HeLa cells.
AB  - The aim of this study was to determine whether heat-shock pretreatment exerted a
      protective effect against sorbitol-induced apoptotic cell death in K562, U937 and
      HeLa cell lines and whether such protection was associated with a decreased
      cytochrome c release from mithocondria and a decreased activation of caspase-9
      and -3. Following heat-shock pretreatment (42 +/- 0.3 degrees C for 1 hr), these
      cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA
      fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat
      shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced
      apoptosis in these different cell lines with a marked activation of caspase-9 and
      caspase-3, whereas heat-shock pretreatment before sorbitol exposure, induced
      expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and
      subsequent activation of caspase-9 and caspase-3. Similarly, overexpression of
      HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation
      as well as cell death. Furthermore, we showed that the mRNA expression of iNOS
      decreased during both the heat-shock treatment and heat-shock pretreatment before
      sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase
      (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before
      sorbitol exposure. We conclude that, heat-shock pretreatment protects different
      cell lines against sorbitol-induced apoptosis through a mechanism that is likely
      to involve SOD family members.

PMID- 19598259
TI  - CD44-positive cells are responsible for gemcitabine resistance in pancreatic
      cancer cells.
AB  - Accumulating evidence suggests that tumors are composed of a heterogeneous cell
      population with a small subset of cancer stem cells (CSCs) that sustain tumor
      formation and growth. Recently, there have been efforts to explain drug
      resistance of cancer cells based on the concept of CSCs having an intrinsic
      detoxifying mechanism. In the present study, to investigate the role of CSCs in
      acquiring chemoresistance in pancreatic cancer, gemcitabine-resistant cells were
      established by exposure to serially escalated doses of gemcitabine in HPAC and
      CFPAC-1 cells. Gemcitabine-resistant cells were more tumorigenic in vitro and in
      vivo, and had greater sphere-forming activity than parental cells. After high
      dose gemcitabine treatment to eliminate most of the cells, CD44(+) cells
      proliferated and reconstituted the population of resistant cells.
      CD44(+)CD24(+)ESA(+) cells remained as a small subset in the resistant cell
      population. Among ATP-binding cassette (ABC) transporters, which are known as the
      mechanism of drug resistance in CSCs, ABCB1 (MDR1) was significantly augmented
      during the acquisition of drug resistance. ABC transporter inhibitor verapamil
      resensitized the resistant cells to gemcitabine in a dose-dependent manner and
      RNA interference of CD44 inhibited the clonogenic activity of resistant cells. In
      human pancreatic cancer samples, CD44 expression was correlated with histologic
      grade and the patients with CD44-positive tumors showed poor prognosis. These
      data indicate that cancer stem-like cells were expanded during the acquisition of
      gemcitabine resistance and in therapeutic application, targeted therapy against
      the CD44 or ABC transporter inhibitors could be applied to overcome drug
      resistance in the treatment of pancreatic cancer.

PMID- 19598260
TI  - Drug-regulatable cancer cell death induced by BID under control of the tissue
      specific, lung cancer-targeted TTS promoter system.
AB  - Gene therapy and virotherapy are among the approaches currently being used to
      treat lung cancer. The success of cancer gene therapy depends on treatments where
      different types of tumors can be selectively targeted and destroyed without
      affecting normal cells and tissue. Previously, we described a promoter system
      (TTS) that we designed that is specifically targeted to lung cancer cells but
      which does not affect other types of cells including stem cells. In our study, we
      have enhanced the utility of the TTS system by inserting the pro-apoptotic gene
      BH3 domain interacting death agonist (Bid) into the TTS promoter system (TTS/Bid)
      to create a drug regulatable lung cancer-specific gene therapy. A recombinant
      adenoviral vector was used to introduce TTS/Bid (Ad-TTS/Bid) into lung cancer
      cells. BID expression and apoptosis occurred in A549 pulmonary adenocarcinoma
      cells but little Bid expression or apoptosis occurred in MCF7 breast cancer cells
      or in normal human lung fibroblasts. The use of cisplatin enhanced the processing
      of full length BID to t-BID which significantly increased lung cancer-specific
      cell death. In in vivo experiments, intraperitonal injection of cisplatin
      enhanced the antitumor effects of the vector in a lung cancer xeno-graft mouse
      model. Moreover, dexamethasone effectively suppressed exogenous BID expression
      and the antitumor effect of Ad-TTS/Bid both in vitro and in vivo. Here, we
      describe the efficacy of the use of cisplatin and dexamethasone with the anti
      lung cancer promoter system (Ad-TTS/Bid) for a safe and effective gene therapy
      against advanced lung cancer.

PMID- 19598261
TI  - Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      in smokers from 3 populations with different risks of lung cancer.
AB  - Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower
      risk of lung cancer (LC), compared with white smokers, even after accounting for
      smoking history. Because variation in carcinogen exposure/metabolism may occur
      separately of smoking amount, we compared urinary biomarkers of uptake and
      detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-a potent
      lung carcinogen-among 578 smokers in these ethnic/racial groups in Hawaii. We
      measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
      and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL + NNAL-Gluc) and
      the NNAL detoxification ratio (NNAL-Gluc:NNAL). Native Hawaiians and Japanese
      Americans had lower age- and sex-adjusted mean total NNAL, compared with whites.
      When further adjusting for urinary nicotine equivalents (the sum of nicotine,
      cotinine, trans-3'-hydroxycotinine and their respective glucuronides), only the
      difference between Japanese-Americans and whites was eliminated. Therefore,
      consistent with their lower LC risk, a lower cigarette smoke exposure explains
      the lower NNK dose of Japanese-Americans, but it does not explain that of Native
      Hawaiians. The mean detoxification ratio was also lower in Native Hawaiians and
      Japanese-Americans, compared with whites, even after adjusting for nicotine
      equivalents (p < 0.0001). Lower NNAL glucuronidation in Native Hawaiians might
      contribute to their increased LC risk; however, this is inconsistent with the low
      glucuronidation ratio similarly observed in the low-risk Japanese-American group
      and because Native Hawaiians had lower total NNAL levels. Thus, exposure and
      detoxification of NNK are unlikely to explain, by themselves, the differences in
      LC risk among the 3 populations studied.

PMID- 19598262
TI  - Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its
      association with chemoresistance to carboplatin.
AB  - Clear cell carcinoma (CCC) of the ovary is known to be highly resistant to
      platinum-based chemotherapy. The purpose of our study was to identify a candidate
      protein that is associated with chemoresistance of CCC and to investigate the
      specific mechanism of chemoresistance conferred by the identified protein.
      Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells
      using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx
      A4 levels were elevated in CCC cells compared with non-CCC cells as determined by
      real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx
      A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated
      significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors
      compared with ovarian serous and endometrioid tumors (p < 0.01). Anx A4
      transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42
      microM) compared with control cells (IC50 = 23 microM) as determined by modified
      MTT assay. Intracellular platinum levels were significantly lower in Anx A4
      transfected cells compared with control cells after carboplatin treatment (p =
      0.0020) and after an additional 360 min of carboplatin-free incubation (p =
      0.0004), as measured by atomic absorption spectrophotometry. Expression of Anx A4
      is elevated in ovarian CCC tumors and is associated with chemoresistance in
      cultured ovarian cancer cells. These results demonstrate that Anx A4 confers
      chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus,
      Anx A4 may represent a novel therapeutic target of chemoresistance in patients
      with ovarian CCC.

PMID- 19598263
TI  - Modified heparins inhibit integrin alpha(IIb)beta(3) mediated adhesion of
      melanoma cells to platelets in vitro and in vivo.
AB  - The adhesion of tumor cells with platelets is important in the process of tumor
      metastasis. A huge work has indicated that anti-adhesion is an effective strategy
      for metastasis inhibition. In this article, we assess the role of platelet
      integrin alpha(IIb)beta(3) in adhesion of melanoma cells to platelets and the
      effects of heparin and modified heparins on the adhesion in vitro and in vivo. We
      show that platelet integrin alpha(IIb)beta(3) is involved in the interaction of
      human melanoma A375 cells with platelets, and the high affinity epitope resides
      on the alpha(IIb) subunit rather than beta(3) subunit. Heparin sulfate-like
      proteoglycans on tumor cell surface are implicated in the adhesion of A375 cells
      to integrin alpha(IIb)beta(3). We also show that RO-heparin, CR-heparin, N-2,3-DS
      heparin and 2,3-O-DS-heparin can significantly inhibit A375 cells binding to the
      CHO cells expressing integrin alpha(IIb)beta(3) under static and flow conditions,
      and remarkably inhibit the adhesion of A375 cells to the immobilized platelet
      layers under flow conditions. We find that A375 cells and B16F10 cells are
      arrested in the pulmonary vessels and adhered to platelets, and the initial
      interaction of tumor cells with platelets in lung vessel and long-term
      establishment of metastatic foci can be inhibited by heparin as well as CR
      heparin and N-2,3-DS-heparin. These data suggest that modified heparins can
      inhibit tumor cell-platelet interaction mediated by platelet integrin
      alpha(IIb)beta(3) and modified heparins may be a potential substitute for heparin
      in inhibiting tumor metastasis.

PMID- 19598264
TI  - Cytosolic accumulation of HPV16 E7 oligomers supports different transformation
      routes for the prototypic viral oncoprotein: the amyloid-cancer connection.
AB  - E7 is the major transforming activity in human papillomaviruses, a causal agent
      for cervical cancer. HPV16 E7 is a small protein with a natively unfolded domain
      for which dozens of specific cellular targets were described, and represents a
      prototypical oncoprotein among small DNA tumor viruses. The protein can form
      spherical oligomers with amyloid-like properties and chaperone activity.
      Conformation specific antibodies locate endogenous oligomeric E7 species in the
      cytosol of 3 model cell lines, strongly co-localizing with amyloid structures and
      dimeric E7 localizes to the nucleus. The cytosolic oligomeric E7 appear as the
      most abundant species in all cell systems tested. We show that nuclear E7 levels
      are replenished dynamically from the cytosolic pool and do not result from
      protein synthesis. Our results suggest that long-term events related to de
      repression of E7 would cause accumulation of excess E7 into oligomeric species in
      the cytosol. These, together with the known target promiscuity of E7, may allow
      interactions with many of the non-pRb dependent targets described. This
      hypothesis is further supported by the detection of E7 oligomers in the cytosol
      of cancerous cells from tissue biopsies.

PMID- 19598265
TI  - How to obtain statistically converged MM/GBSA results.
AB  - The molecular mechanics/generalized Born surface area (MM/GBSA) method has been
      investigated with the aim of achieving a statistical precision of 1 kJ/mol for
      the results. We studied the binding of seven biotin analogues to avidin, taking
      advantage of the fact that the protein is a tetramer with four independent
      binding sites, which should give the same estimated binding affinities. We show
      that it is not enough to use a single long simulation (10 ns), because the
      standard error of such a calculation underestimates the difference between the
      four binding sites. Instead, it is better to run several independent simulations
      and average the results. With such an approach, we obtain the same results for
      the four binding sites, and any desired precision can be obtained by running a
      proper number of simulations. We discuss how the simulations should be performed
      to optimize the use of computer time. The correlation time between the MM/GBSA
      energies is approximately 5 ps and an equilibration time of 100 ps is needed. For
      MM/GBSA, we recommend a sampling time of 20-200 ps for each separate simulation,
      depending on the protein. With 200 ps production time, 5-50 separate simulations
      are required to reach a statistical precision of 1 kJ/mol (800-8000 energy
      calculations or 1.5-15 ns total simulation time per ligand) for the seven avidin
      ligands. This is an order of magnitude more than what is normally used, but such
      a number of simulations is needed to obtain statistically valid results for the
      MM/GBSA method.

PMID- 19598267
TI  - Absorption and fluorescence emission spectroscopic characters of naphtho
      homologated yy-DNA bases and effect of methanol solution and base pairing.
AB  - A comprehensive theoretical study of electronic transitions of naphtho
      homologated base analogs, namely, yy-T, yy-C, yy-A, and yy-G, was performed. The
      nature of the low-lying excited states is discussed, and the results are compared
      with those from experiment and also with those of y-bases. Geometrical
      characteristics of the lowest excited singlet pipi* and npi* states were explored
      using the CIS method, and the effects of methanol solution and paring with their
      complementary natural bases on the relevant absorption and emission spectra of
      these modified bases were examined. The calculated excitation and emission
      energies agree well with the measured data, where experimental results are
      available. In methanol solution, the fluorescence from yy-A and yy-G would be
      expected to occur around 539 and 562 nm, respectively, suggesting that yy-A is a
      green-colored fluorophore, whereas yy-G is a yellow-colored fluorophore. The
      methanol solution was found to red-shift both the absorption and emission maxima
      of yy-A, yy-T, and yy-C, but blue-shift those for yy-G. Generally, though base
      pairing has no significant effects on the absorption and fluorescence maxima of
      yy-A, yy-C, and yy-T, it blue-shifts those for yy-G.

PMID- 19598266
TI  - Using electronic polarization from the internal continuum (EPIC) for
      intermolecular interactions.
AB  - Recently, the vacuum-phase molecular polarizability tensor of various molecules
      has been accurately modeled (Truchon et al., J Chem Theory Comput 2008, 4, 1480)
      with an intramolecular continuum dielectric model. This preliminary study showed
      that electronic polarization can be accurately modeled when combined with
      appropriate dielectric constants and atomic radii. In this article, using the
      parameters developed to reproduce ab initio quantum mechanical (QM) molecular
      polarizability tensors, we extend the application of the "electronic polarization
      from internal continuu" (EPIC) approach to intermolecular interactions. We first
      derive a dielectric-adapted least-square-fit procedure similar to RESP, called
      DRESP, to generate atomic partial charges based on a fit to a QM abinitio
      electrostatic potential (ESP). We also outline a procedure to adapt any existing
      charge model to EPIC. The ability of this to reproduce local polarization, as
      opposed to uniform polarization, is also examined leading to an induced ESP
      relative root mean square deviation of 1%, relative to ab initio, when averaged
      over 37 molecules including aromatics and alkanes. The advantage of using a
      continuum model as opposed to an atom-centered polarizable potential is
      illustrated with a symmetrically perturbed atom and benzene. We apply EPIC to a
      cation-pi binding system formed by an atomic cation and benzene and show that the
      EPIC approach can accurately account for the induction energy. Finally, this
      article shows that the ab initio electrostatic component in the difficult case of
      the H-bonded 4-pyridone dimer, a highly polar and polarized interaction, is well
      reproduced without adjusting the vacuum-phase parameters.

PMID- 19598269
TI  - A whisper from the silent lung zone.
AB  - Multiple breath inert gas washout (MBW) is now regarded as "an insightful, sound,
      and useful tool to explore the lung and its response to injury in all of its
      compartments". We describe the important finding of pronounced intra-acinar
      airways response to indirect challenge testing, detected using MBW but missed by
      spirometry, in an adolescent with evidence of airway inflammation, and a
      background of severe respiratory syncytial virus (RSV) infection as an infant.
      These tests were performed as part of an 18-year follow up of a cohort with
      severe RSV infection (requiring hospitalization) in the first year of life, and
      has previously reported significantly higher rates of symptoms of allergic asthma
      and other features of atopic disease at 13 years in comparison to age matched
      controls. Small airway dysfunction and ventilation inhomogeneity have emerged as
      important features of early respiratory disease processes, and this case report
      provides further evidence supporting its important role in reactive airways
      disease.

PMID- 19598268
TI  - Mechanism of pH-sensitive polymer-assisted protein refolding and its application
      in TGF-beta1 and KGF-2.
AB  - Refolding of proteins at high concentrations often results in non-productive
      aggregation. This study, through a unique combination of spectroscopic and
      chromatographic analyzes, provides biomolecular evidence to demonstrate the
      ability of Eudragit S-100, a pH-responsive polymer, to enhance refolding of
      denatured-reduced lysozyme at high concentrations. The addition of Eudragit in
      the refolding buffer significantly increases lysozyme refolding yield to 75%,
      when dilution refolding was conducted at 1 mg/mL lysozyme. This study shows
      evidence of an electrostatic interaction between oppositely charged lysozyme and
      the Eudragit polymer during refolding. This ionic complexing of Eudragit and
      lysozyme appears to shield exposed hydrophobic residues of the lysozyme refolding
      intermediates, thus minimizing hydrophobic-driven aggregation of the molecules.
      Importantly, results from this study show that the Eudragit-lysozyme
      bioconjugation does not compromise refolded protein structure, and that the
      polymer can be readily dissociated from the protein by ion exchange
      chromatography. The strategy was also applied to refolding of TGF-beta1 and KGF
      2.

PMID- 19598270
TI  - Validity and utility of subtyping anorexia nervosa.
AB  - OBJECTIVE: The purpose of this article is to review the available literature that
      addresses the predictive validity and utility of subtyping patients with anorexia
      nervosa (AN) into binge/purge and restrictor subtypes. METHOD: Literature was
      reviewed including studies that compared individuals with subtype diagnoses on
      clinical and outcome variables as well as more recent research examining the
      frequency of diagnostic crossover. RESULTS: Several studies found that in general
      the binge/purge subtype patients have more psychopathology, tend to be older, and
      tend to have a worse outcome. More recent studies which have examined diagnostic
      crossover suggest that the rate of crossover from the restrictor subtype to the
      binge/purge subtype is substantial. Crossover from the binge/purge to the
      restrictor subtype appears to occur less commonly. There is also literature
      documenting crossover from AN to bulimia nervosa (BN) and a small literature
      looking at crossover from BN to AN. DISCUSSION: The results of this article
      suggest that although there is generally progression from restrictor AN to
      binge/purge AN to BN in a sizeable number of patients, other crossover patterns
      can be seen as well and the amount of crossover is quite large. This suggests a
      lack of predictive validity for subtypes.

PMID- 19598271
TI  - Using index of ventilation to assess response to treatment for acute pulmonary
      exacerbation in children with cystic fibrosis.
AB  - BACKGROUND: The use of alternative more sensitive measures has become a focus of
      research in CF. The utility of indexes of ventilation, Lung Clearance Index (LCI)
      and peak aerobic capacity (peak VO(2)), were studied as assessment tools in
      gauging response to intravenous (IV) therapy in acute pulmonary exacerbation, in
      comparison to the more commonly used index of forced expiratory volume in 1 sec
      (FEV(1)). The utility of a previously published clinical score was further
      explored. METHODS: Patients aged 8-18 years admitted for IV antibiotic treatment
      of a pulmonary exacerbation were recruited. Spirometry, plethysmography, multiple
      breath nitrogen washout, exercise testing, and Cystic Fibrosis Clinical Score
      (CFCS) were performed on admission and prior to discharge. RESULTS: Twenty-eight
      patients were recruited, with a mean (range) age of 13.7 (8; 17) years, 16 female
      and 12 male. Mean (range) admission FEV(1) was 61.4 (28; 92)% predicted, or z
      score -3.09 (-6.15; -0.52), FVC 83.0 (38; 120)% predicted, or z-score -1.71 (
      5.66; -1.17), and Shwachman-Kulczycki 68.9 (50; 90). FEV(1) increased by 7.0% (P
      < 0.01) from admission to discharge. Mean (range) admission LCI, 10.10 (6.87;
      14.83), decreased by 3.8% (P = 0.03). Mean (range) admission peak VO(2)
      (ml/kg/min), 31.2 (23.4; 45.4), increased on discharge by 6.6% (P < 0.01).
      Proposed clinical thresholds, based on the available variability data,
      highlighted the heterogeneity of response in lung function tests. Mean (range)
      admission CFCS, 26.5 (19; 39), decreased to 19.9 (13; 31) on discharge, a 25.2%
      improvement (P < 0.01). CFCS demonstrated improvement in 27 of 28 patients.
      Changes in peak VO(2) (r = -0.50, P = 0.02) and LCI (r = 0.48, P = 0.01)
      correlated with CFCS change. CONCLUSIONS: In children with mild-to-moderate CF,
      whilst statistically significant improvement in both LCI and peak VO(2) were
      seen, heterogeneity of response was evident. The most consistent improvement was
      seen in CFCS. Correlation of LCI and peak VO(2) with change in clinical score
      (CFCS) was seen. The full clinical significance of these changes in LCI and peak
      VO(2) needs to be evaluated further with additional variability data. The CFCS
      may be useful in the assessment of response to treatment in CF but requires
      formal validation.

PMID- 19598273
TI  - Inter-observer agreement between physicians, nurses, and respiratory therapists
      for respiratory clinical evaluation in bronchiolitis.
AB  - Care providers for children with bronchiolitis use various tools to evaluate
      respiratory status. The use of a single tool by different types of care provider
      requires a high level of inter-observer agreement, an aspect rarely studied. This
      study, involving 82 physicians, nurses, and respiratory therapists aimed to
      evaluate inter-observer agreement for clinical evaluations in children
      hospitalized for a first episode of bronchiolitis. Respiratory evaluation
      included three frequently reported parameters of respiratory status: respiratory
      rate, retraction signs, and wheezing. The frequency of concordance for observers
      from the same and from different care provider groups was assessed using a
      weighted kappa statistic and considering all possible combinations of care
      providers. We also calculated inter-provider agreement as a function of patient
      age, regardless of care provider type. Overall inter-observer agreement for all
      provider pairs was 93.1%, with a weighted kappa statistic of 0.72 (95% CI, 0.66
      0.78), indicating substantial agreement, with no difference as a function of pair
      composition. Inter-observer agreements for the various age groups ranged from 87%
      to 93%, with kappa scores ranging from 0.62 to 0.78. We conclude that a simple
      clinical evaluation for respiratory status assessment has a high level of inter
      observer agreement within and between physicians, nurses and respiratory
      therapists. Thus, once the validity of this test has been confirmed in a large
      population sample, it should be possible to use this test to monitor children
      hospitalized with bronchiolitis and as an endpoint in clinical trials.

PMID- 19598272
TI  - 'Difficult asthma': can symptoms be controlled in a structured environment?
AB  - OBJECTIVE: Difficult asthma implies persistent asthma symptoms despite therapy
      with high doses of inhaled corticosteroids. The objective was to evaluate
      children with difficult asthma in a setting that excludes aggravating factors
      such as poor treatment adherence and adverse environmental influences. PATIENTS
      AND METHODS: Sixty children (> or =6 years) had been referred because of
      difficult asthma to the rehabilitation centre over a period of 10 years. The
      diagnosis of poor asthma symptom control was confirmed if exacerbations continued
      during stay in the centre or if symptoms interfered with daily activities at
      least 3 times a week. RESULTS: The median stay at the centre was 5 months. In
      four patients a diagnosis other than asthma was made. In five patients symptom
      control remained difficult. In the remaining 51 children, asthma symptoms became
      well controlled. Many factors contributed to poor asthma control in the home
      setting: poor treatment adherence (n = 32), parental smoking (n = 22), allergen
      exposure (n = 10). Psychosocial problems occurred in 36 children. Contributing
      factors often co-existed. During stay at the centre, lung function improved in
      the group with well controlled asthma symptoms (P < 0.001) but not in the group
      with continued poor symptom control. In the majority of children who obtained
      good symptom control, this persisted in the years following discharge.
      CONCLUSION: Of 60 children referred with a diagnosis of difficult asthma, optimal
      medical management in a structured environment resulted in good symptom control
      in 51 patients; symptom control remained poor in 5 patients, a diagnosis other
      than asthma was made in 4 patients.

PMID- 19598274
TI  - An unusual case of traumatic pneumatocele in a nine-year-old girl: a bronchial
      tear with clear bronchial laceration.
AB  - Post-traumatic pneumatoceles (traumatic pulmonary pseudocysts) after blunt
      thoracic trauma are not frequently observed. It is widely accepted that
      pneumatoceles are caused by compression of the lung resulting in bursting
      parenchyma, followed by decompression of the chest with negative intrathoracic
      pressure. We present a case of post-traumatic pneumatocele in a nine-year-old
      girl who was crushed under the tailboard of a horse hamper. A multislice CT of
      the thorax clearly demonstrated a bronchial laceration pointing to bronchial
      disruption as an additional causative mechanism.

PMID- 19598276
TI  - Relations between depressive and anxious symptoms and quality of life in
      caregivers of children with cystic fibrosis.
AB  - Little is known about depressive and anxious symptoms and quality of life (QOL)
      in caregivers of children with cystic fibrosis (CF). The aims of this study were
      to: (1) assess rates of female and male caregiver depressive and anxious
      symptoms, and (2) evaluate relations between depressive and anxious symptoms,
      caregiver QOL, and health outcomes. PATIENTS AND METHODS: Eligible participants
      were caregivers of children with CF who completed three questionnaires assessing
      depressive and anxious symptoms and caregiver QOL during routine CF Clinic
      appointments. RESULTS: Rates of depressive and anxious symptoms were elevated in
      female and male caregivers of children with CF. Rates were higher for anxious
      (51% for females, 43% for males) than depressive symptoms (20-28% for females; 14
      31% for males). Female caregiver depressive symptoms increased as child lung
      functioning decreased. As depressive and anxious symptoms increased, caregiver
      QOL decreased. In addition, female caregiver depressive and anxious symptoms were
      positively correlated with male caregiver anxious and depressive symptoms in a
      small subsample of couples. CF disease severity and caregiver depressive symptoms
      predicted caregiver QOL. CONCLUSION: Rates of depressive and anxious symptoms are
      high among caregivers of children with CF. The results of this study highlight
      the need to screen for female and male caregiver depressive and anxious symptoms
      in the CF Clinic as CF Team members are well positioned to provided assistance
      around solving CF-related challenges. In addition, alleviation of depressive and
      anxious symptoms could potentially lead to improvements in the psychological
      functioning and well-being of caregivers of children with CF.

PMID- 19598277
TI  - Congenital chylothorax: clinical course and prognostic significance.
AB  - OBJECTIVE: To determine the underlying etiology, associated malformations,
      clinical course, and prognostic significance of congenital chylothorax. STUDY
      DESIGN: A retrospective analysis of 11 neonates admitted to our neonatal
      intensive care unit with congenital chylothorax between January 2000 and June
      2008. The post-discharge clinical and developmental course was evaluated by a
      telephone survey performed in July 2008. RESULTS: Antenatal diagnosis was
      established in 9 out of 11 infants by ultrasound examination; 5 had intrauterine
      pleural drainage. Eight infants had either structural or chromosomal
      abnormalities. The postnatal treatment included mechanical ventilation, drainage
      of pleural fluid and feeding with enriched medium chain triglyceride formula.
      Somatostatin was administered in one case. Six patients developed nosocomial
      infections. Two patients died after resolution of the chylothorax from
      deteriorating renal failure. Seven patients were traced for follow up and six of
      them achieved age appropriate developmental milestones. CONCLUSION: The recovery
      from chylothorax and future prognosis were dependent on the underlying etiology.
      Chylothorax was often a secondary event, with apparently favorable clinical and
      developmental prognosis when the underlying or/and associated condition was
      treatable.

PMID- 19598278
TI  - Effect of mutator P. aeruginosa on antibiotic resistance acquisition and
      respiratory function in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis patients suffer from recurrent bacterial infections
      that result in progressive deterioration of their respiratory function. Despite
      intensive antibiotic treatment, Pseudomonas aeruginosa is the main cause of such
      infections, with clones progressively developing multiple antibiotic resistance.
      We determined the relationship between the presence of P. aeruginosa mutator
      strains and cystic fibrosis clinical characteristics. METHODS: We analyzed 136
      strains of P. aeruginosa isolated from the expectorations of 36 CF patients. On
      all strains, mutation frequencies were determined by the mutation rate to
      rifampicin, and antibiotic susceptibility was determined by the disk diffusion
      method. The epidemiological relatedness of these 136 P. aeruginosa strains was
      studied by pulsed-field gel electrophoresis. The appearance of new antibiotic
      resistance by sequential analysis of genotypically identical strains was
      determined. Lung function test results, that is, forced expiratory volume in 1
      sec and vital capacity, were also recorded from these patients. RESULTS: We
      showed that bacteria with an enhanced mutation rate increase the rate of
      acquisition of new antibiotic resistance threefold and are associated with the
      deterioration of lung function. CONCLUSIONS: This study demonstrates the effect
      of mutator bacteria on the efficiency of patient treatment and on their
      respiratory function. Given the consequence of antibiotic treatment failure and
      lung deterioration on the prognosis of CF patients, antibiotic treatment
      strategies may need to be optimized to prevent the emergence of mutator clones.

PMID- 19598279
TI  - Overexpression of Zip-2 mRNA in the leukocytes of asthmatic infants.
AB  - The increase in prevalence of asthma is strongly dependent on environmental
      factors, including foods. Significant decreases in the intake of dietary zinc may
      be an important contributing factor to the increasing incidence of asthma. As
      zinc can not passively diffuse across cell membranes, specific zinc transporters
      are required for zinc influx and efflux. There are two identified gene families
      involved in zinc homeostasis, ZnT transporters and ZIP transporters. In this
      study, we aimed to investigate the expression of these zinc transporters mRNA in
      the leukocytes of asthmatic infants. Asthmatic infants (n = 9) and healthy
      infants (n = 9) were included in this study. Five zinc transporters were chosen:
      ZnT-1, ZnT-3, ZnT-5, ZIP-1, and ZIP-2. Levels of zinc were determined in serum
      and expression of zinc transporters mRNA were measured. Serum zinc levels were
      significantly lower in asthmatic infants (P < 0.01); Expression of ZnT-1, ZnT-3,
      ZnT-5, ZIP-1 mRNA were not significantly different between two groups, but
      expression of ZIP-2 mRNA was significantly higher (P < 0.01) in the asthmatic
      group than the control group. In conclusion, overexpression of ZIP-2 mRNA was
      found in the leukocytes of asthmatic infants.

PMID- 19598280
TI  - Ionic determinants of exhaled breath condensate pH before and after exercise in
      adolescent athletes.
AB  - BACKGROUND: The pH of exhaled breath condensate (EBC) of adolescent athletes
      engaged in vigorous physical activity is low compared to healthy controls;
      however, the ionic determinants of EBC pH and the acute effects of exercise on
      those determinants have not been definitively established. OBJECTIVES: This study
      had two purposes: (1) to identify the ionic composition of EBC before and after
      exercise, and (2) to examine the effects of sample deaeration on EBC pH and
      composition. METHODS: EBC ionic composition was determined by ion chromatography
      and correlated with pH measured before and after deaeration. Bicarbonate
      concentration was calculated from the ion balance of other measured species and
      pH. RESULTS: EBC pH displayed a bimodal distribution, included values lower than
      expected for healthy individuals, and was correlated exclusively with volatile
      species, namely ammonia (mean concentration = 215 microM) and acetic (31.7
      microM) and propionic acids (10.0 microM). Following exercise, raw EBC pH and
      ammonia concentration increased while propionic acid concentration fell.
      Following deaeration, EBC pH increased by one unit on average; however, the pH of
      samples with unusually low pH did not change significantly, and the
      concentrations of several ionic species were altered in a manner that cannot be
      explained in terms of volatility. CONCLUSIONS: We conclude that in healthy
      adolescents, exercise results in an acute increase in raw EBC pH in association
      with an increase in ammonium and a decrease in propionate concentration. Since
      exercise increases systemic ammonia and urea (which is hydrolyzed by oral
      bacteria to form ammonia), we propose that the likely source of these changes is
      gas-phase diffusion from epithelial and oral surface liquids and to a lesser
      extent, from pulmonary circulation.

PMID- 19598281
TI  - The effects of racemic albuterol versus levalbuterol in very low birth weight
      infants.
AB  - Bronchodilators have been used in premature infants. Levalbuterol (LEV) an R
      isomer of Albuterol has fewer hemodynamic side effects than Racemic Albuterol
      (RAC) in adults and children. In a retrospective study we sought to investigate
      the effects of LEV (0.31 mg) versus RAC (1.25 mg) in very low-birth weight
      infants (VLBW) who were treated with a beta-2 agonist for > or =2 weeks. Medical
      records (between January 2001 and December 2006) were reviewed for patients'
      demographics, medications use, hemodynamic and respiratory parameters,
      hypokalemia and hyperglycemia. Among 811 VLBW infants who were admitted to our
      NICU, 16 infants received RAC and 31 infants received LEV for > or =2 weeks.
      Infants who received RAC were younger, smaller, and received less Ipratropium
      Bromide (IB) than infants who received LEV [26.1 +/- 1.2 weeks vs. 28.1 +/- 3.7
      weeks (P = 0.01), 817 +/- 211 g vs. 1,127 +/- 589 g (P = 0.01) and 2/16 (12%) vs.
      15/31 (48%; P = 0.01); respectively]. In infants treated exclusively with RAC or
      LEV without IB, mean arterial blood pressures were lower in the RAC (n = 14) than
      the LEV group (n = 16, P = 0.05 by general linear model with repeated measures);
      however there were no differences in daily heart rates, oxygen supplementations,
      oxygen saturations, or respiratory rates. Also there were no differences between
      the two groups in hypokalemia or hyperglycemia. We conclude that LEV at a dose of
      0.31 mg might have an indication in VLBW infants who are at risk for hemodynamic
      instability.

PMID- 19598282
TI  - Olfactory and amygdalar structures of the chicken ventral pallium based on the
      combinatorial expression patterns of LIM and other developmental regulatory
      genes.
AB  - We compared the combinatorial expression patterns of several LIM domain
      containing regulatory genes in the ventrolateral pallium of mouse and chicken, in
      order to identify the homologues of the ventral pallial amygdala and other
      olfactory structures in birds. Lmo3, Lmo4, Lhx2, and Lhx9 showed comparable
      expression patterns in the telencephalon of mouse and chicken, which allowed
      distinction of the ventrolateral pallium and, particularly, the ventral pallial
      amygdala and entorhinal cortex. Lmo3 was expressed in most of the ventrolateral
      pallium in both species, including, in chicken, the piriform cortex and dorsal
      ventricular ridge (mesopallium, nidopallium, and arcopallium) and, in mouse, the
      piriform cortex, most of the claustral complex, and the pallial amygdala. Lhx9
      was differentially expressed in the ventral pallium, where it was restricted to
      its rostral (olfactory bulb) and caudal (amygdalar and entorhinal) poles. In the
      caudal pole, expression of Lhx9 overlapped that of its paralog Lhx2. According to
      these expression patterns, the chicken ventral pallial amygdala appears to
      include the caudal dorsolateral pallium, the caudal nidopallium, and the whole
      arcopallium, and each one relates to a distinct ventricular sector. Finally, the
      combinatorial expression patterns of Lmo3, Lhx9, and Lmo4 distinguished four
      distinct subdivisions in the superficial, olfactorecipient area of the chicken
      ventral pallium, which appear comparable to the piriform, entorhinal,
      amygdalopiriform, and amygdalar cortices of mammals. The results are discussed in
      the context of the two existing, opposite views on the homology of the dorsal
      ventricular ridge of sauropsids and in terms of the evolution of pallial
      derivatives.

PMID- 19598283
TI  - Sequential onset of presynaptic molecules during olfactory sensory neuron
      maturation.
AB  - Differentiated olfactory sensory neurons express specific presynaptic proteins,
      including enzymes involved in neurotransmitter transport and proteins involved in
      the trafficking and release of synaptic vesicles. Studying the regulation of
      these presynaptic proteins will help to elucidate the presynaptic differentiation
      process that ultimately leads to synapse formation. It has been postulated that
      the formation of a synapse between the axons of the sensory neurons and the
      dendrites of second order neurons in the olfactory bulb is a critical step in the
      processes of sensory neuron maturation. One approach to study the relationship
      between synaptogenesis and sensory neuron maturation is to examine the expression
      patterns of synaptic molecules through the olfactory neuron lineage. To this end
      we designed specific in situ hybridization probes to target messengers for
      proteins involved in presynaptic vesicle release. Our findings show that, as they
      mature, mouse olfactory neurons sequentially express specific presynaptic genes.
      Furthermore, the different patterns of expression of these presynaptic genes
      suggest the existence of discrete steps in presynaptic development: genes
      encoding proteins involved in scaffolding show an early onset of expression,
      whereas expression of genes encoding proteins involved in the regulation of
      vesicle release starts later. In particular, the signature molecule for
      glutamatergic neurons vesicle glutamate transporter 2 shows the latest onset of
      expression. In addition, contact with the targets in the olfactory bulb is not
      controlling presynaptic protein gene expression, suggesting that olfactory
      sensory neurons follow an intrinsic program of development.

PMID- 19598284
TI  - Dendritic synthesis and release of the neuropeptide galanin: morphological
      evidence from studies on rat locus coeruleus neurons.
AB  - Dendritic synthesis and release of neuropeptides have been demonstrated in
      hypothalamic neurosecretory neurons. Here we tested whether this mechanism may be
      applicable to galanin in rat locus coeruleus (LC) neurons. Light and electron
      microscopic immunocytochemistry demonstrated the occurrence of galanin peptide in
      secretory granules within dendritic processes. In situ hybridization at the light
      and electron microscopic level showed galanin mRNA in these LC processes.
      Moreover, the levels of the transcript and its extension into the dendrites were
      significantly increased by reserpine treatment. Finally, evidence for exocytotic
      release from large dense-core vesicles in LC dendrites was obtained by using
      tannic acid-treated slices. Taken together, these results indicate that galanin
      can be synthesized in, and possibly released from, LC. These data support a key
      function of the neuropeptide galanin as an auto-paracrine local modulator in a
      major, strongly divergent monoaminergic regulatory system.

PMID- 19598286
TI  - Novel lbeta-methylcarbapenems having cyclic sulfonamide moieties: synthesis and
      evaluation of in-vitro biological activity - part II.
AB  - The synthesis of a new series of 1beta-methylcarbapenems having cyclic
      sulfonamide moieties is described. Their in-vitro antibacterial activities
      against both Gram-positive and Gram-negative bacteria were tested and the effect
      of a substituent on the pyrrolidine ring was investigated. One particular
      compound IIIe having a [1,2,5]thiadiazolidin 1,1-dioxide moiety showed the most
      potent antibacterial activity.

PMID- 19598285
TI  - Vagal gustatory reflex circuits for intraoral food sorting behavior in the
      goldfish: cellular organization and neurotransmitters.
AB  - The sense of taste is crucial in an animal's determination as to what is edible
      and what is not. This gustatory function is especially important in goldfish, who
      utilize a sophisticated oropharyngeal sorting mechanism to separate food from
      substrate material. The computational aspects of this detection are carried out
      by the medullary vagal lobe, which is a large, laminated structure combining
      elements of both the gustatory nucleus of the solitary tract and the nucleus
      ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers
      via a simple reflex arc. Details of this reflex circuit were investigated with
      histology and calcium imaging. Biocytin injections into the motor layer labeled
      vagal reflex interneurons that have radially directed dendrites ramifying within
      the layers of primary afferent terminals. Axons of reflex interneurons extend
      radially inward to terminate onto both vagal motoneurons and small, GABAergic
      interneurons in the motor layer. Functional imaging shows increases in
      intracellular Ca++ of vagal motoneurons following electrical stimulation in the
      sensory layer. These responses were suppressed under Ca(++)-free conditions and
      by interruption of the axons bridging between the sensory and motor layers.
      Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3
      hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic
      acid (NMDA) receptors mediate neurotransmission between reflex interneurons and
      vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory
      complex is linked to branchiomotor neurons of the pharynx via a glutamatergic
      interneuronal system.

PMID- 19598287
TI  - 3-imidazolyl-substituted flavans as potential antifungal agents: synthesis,
      stereochemical properties, and antifungal activity.
AB  - A new series of 3-imidazolyl-substituted flavan derivatives being equipped with a
      N-(phenethyl)-azole scaffold as the common pharmacophore of azole antifungals,
      were synthesized. The stereochemical and conformational properties of compounds
      were also characterized by (1)H-NMR data. The results of the antifungal
      evaluation of trans-3-imidazolyl-substituted flavan-4-ones and (Z)-trans-3
      imidazolyl-substituted flavan-4-one oximes in comparison with the reference drug
      fluconazole indicated that most target compounds possessed significant in-vitro
      antifungal activities against the tested fungi, comparable or superior to
      fluconazole.

PMID- 19598288
TI  - Synthesis of (1R,2R)- and (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonates as
      analogues of fosfomycin.
AB  - Cyclohexylammonium (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonate was conveniently
      synthesized from dibenzyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3
      trihydroxypropylphosphonate by a reaction sequence including mesylation,
      hydrolysis of acetal, intramolecular Williamson reaction, and hydrogenation in
      the presence of cyclohexylamine. For dibenzyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3
      trihydroxypropylphosphonates the same approach was not successful, since prior
      the epoxide-ring closure tritylation of HO-C3 in dibenzyl (1R,2R)-2,3-dihydroxy-1
      mesyloxypropylphosphonate was necessary and the hydrogenolysis of dibenzyl
      (1S,2R)-1,2-epoxy-3-trityloxypropylphosphonate yielded a complex reaction
      mixture.

PMID- 19598289
TI  - 6-substituted indolo[1,2-c]quinazolines as new antimicrobial agents.
AB  - A series of 2-o-arylidineaminophenylindoles and their cyclic derivatives
      (indolo[1,2-c]quinazolines) were synthesized. The reactions occurred under
      relatively mild conditions and afforded the desired product in good yields.
      Molecular structures of the synthesized compounds were confirmed by IR, (1)H
      NMR,( 13)C-NMR, MS spectra, and elemental analyses. Furthermore, all the final
      products were screened for in-vitro antibacterial activity against three Gram
      positive and three Gram-negative bacteria and also tested for their inhibitory
      action against three strains of fungi. Compound IIc showed potent activity
      against all the bacterial (except S. typhimurium) and fungal strains. Especially,
      compounds IIi and IIj which have isoquinolyl and pyridyl substituents displayed
      potent antibacterial as well as antifungal activities compared to those of the
      respective standard drugs Ampicillin and Ketoconazole.

PMID- 19598290
TI  - Synthesis and characterization of new liver targeting 5-fluorouracil-cholic acid
      conjugates.
AB  - The objective of this work was to develop a liver-specific antihepato carcinoma
      agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid
      conjugates) were prepared and tested for their chemical characteristics and bio
      distribution properties. The in-vitro stability trial showed 5-FU-cholic acid
      conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic
      solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds
      could be compatible with a fast separation and analysis method to shorten the
      analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in
      different organs of mice at several time points after oral administration were
      evaluated by measuring the concentrations of regenerated 5-FU in organ tissue.
      The results were compared with those of the controls, which was a group of mice
      orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were
      remarkably increased after oral administration of the prodrugs, and were much
      larger than if only orally administered 5-FU. The results suggested the
      feasibility to improve therapeutic efficiency of liver targeting treatments by
      using cholic acid as the vector of drugs.

PMID- 19598291
TI  - Comparing ceramic-metal to metal-metal total hip replacements--a simulator study
      of metal wear and ion release in 32- and 38-mm bearings.
AB  - Our 32 and 38 mm alumina ceramic-on-metal (COM) bearings were run in a hip
      simulator study for comparison with 32 mm metal-on-metal (MOM) controls. The 32
      mm MOM bearings demonstrated an overall wear rate of 1.58 mm(3)/million cycles
      (Mc) that was comparable to previous simulator studies. The peak run-in MOM wear
      rates (10, 15.7 mm(3)/Mc) were higher than in previous simulator studies. There
      was a noticeable graying in color of serum lubricants with MOM wear rates of 2-3
      mm(3)/Mc and with wear rates of 10-15 mm(3)/Mc the serum became much darker. The
      COM lubricants darkened during two "break-away" wear events with wear-rates 5.8
      6.7 mm(3)/Mc. The 32 and 38 mm COM bearings demonstrated overall wear-rates of
      0.38 and 0.29 mm(3)/Mc, approximately four-fold reduced compared to MOM controls.
      The COM wear-rates were also much higher than in the one previous COM study.
      There may be methodological reasons that could explain this discrepancy. Our ion
      concentrations assessed from serum lubricants had Cobalt (Co) 68% and Chromium
      (Cr) 32% for average ratio of metal ion composition (i.e. averaging Co/Cr ratios:
      2.26) in the parent alloy. Comparing Co ion concentrations during run-in, the COM
      bearings represented a 35-fold reduction compared to MOM. At 3.0 Mc, the COM
      represented a 33-fold reduction compared to MOM. Overall, our simulator study
      confirmed previously published advantages of low wear and reduced metal ions with
      the ceramic-metal coupling compared to standard metal-metal bearings.

PMID- 19598292
TI  - Predictors of change in unmet supportive care needs in cancer.
AB  - OBJECTIVE: Patient Reported Outcome (PRO) assessments can assist health
      professionals to tailor their health practices to the individual needs of
      patients and improve patient care over time. The present study assessed
      prospective predictors of unmet supportive care needs in cancer patients over a
      six-month period. METHODS: Participants were recruited from a regional cancer
      treatment centre in Australia and completed the Supportive Care Needs Survey
      (SCNS) at recruitment (n=439; 61.4% response rate) and six months follow-up
      (n=396). Hierarchical logistic regression was used to identify predictors of
      change in unmet needs across each supportive care domain. Predictor variables
      were socio-demographic, treatment and psychosocial factors including depression,
      anxiety, social support, and patient satisfaction. RESULTS: Unmet needs were
      reported by approximately two-thirds of patients at baseline and half of patients
      at six months follow-up. Having unmet needs at baseline was the strongest
      predictor of unmet needs at six months. Longer time since diagnosis was a
      consistent predictor of greater unmet needs, associated with change in
      physical/daily living, psychological and health system and information unmet
      needs over time. By contrast, a complex relationship was found in that patient
      satisfaction, psychosocial and treatment characteristics predicted higher needs
      in some domains and lower needs in others. CONCLUSIONS: Unmet supportive care
      needs persist over time and psychological needs may emerge later in the illness
      continuum. Interventions to meet the needs of longer term cancer survivors are
      needed and should closely articulate with reported supportive care needs.

PMID- 19598293
TI  - First degree relatives of women with breast cancer: who's providing information
      and support and who'd they prefer.
AB  - INTRODUCTION: Mothers, sisters, and daughters of women diagnosed with breast
      cancer have an increased need for factual information, counseling, and emotional
      support. The purpose of this exploratory, descriptive study was to identify the
      information and support needs of Israeli women with a family history of breast
      cancer; discover whether these needs have been met, by whom, and who is the
      preferred source for them. METHODS: 128 healthy Israeli women, aged 18-65, with a
      first degree relative with breast cancer completed the adapted Information and
      Support Needs Questionnaire (ISNQ). RESULTS: Information needs were ranked above
      support needs, especially information about disease prevention. The degree to
      which the needs were met was generally ranked as low, with response to the
      information needs ranking higher than the response to the support needs. The
      doctor was the prime source of choice for the information and support needs.
      CONCLUSION: This study contributes to the understanding of the needs of patients'
      families, provides a framework for the improvement of methods of communication,
      and a basis for constructing information and support systems. In addition, it
      highlights the need for a multidisciplinary, proactive approach in health
      promotion for cancer patients' families.

PMID- 19598294
TI  - What every gastroenterologist needs to know about common anorectal disorders.
AB  - Anorectal complaints are very common and are caused by a variety of mostly benign
      anorectal disorders. Many anorectal conditions may be successfully treated by
      primary care physicians in the outpatient setting, but patients tend not to seek
      medical attention due to embarrassment or fear of cancer. As a result, patients
      frequently present with advanced disease after experiencing significant decreases
      in quality of life. A number of patients with anorectal complaints are referred
      to gastroenterologists. However, gastroenterologists' knowledge and experience in
      approaching these conditions may not be sufficient. This article can serve as a
      guide to gastroenterologists to recognize, evaluate, and manage medically or non
      surgically common benign anorectal disorders, and to identify when surgical
      referrals are most prudent. A review of the current literature is performed to
      evaluate comprehensive clinical pearls and management guidelines for each topic.
      Topics reviewed include hemorrhoids, anal fissures, anorectal fistulas and
      abscesses, and pruritus ani.

PMID- 19598295
TI  - Current management strategy of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) still remains a considerable challenge for
      surgeons. Surgery, including liver transplantation, is the most important
      therapeutic approach for patients with this disease. HCC is frequently diagnosed
      at advanced stages and has a poor prognosis with a high mortality rate even when
      surgical resection has been considered potentially curative. This brief report
      summarizes the current status of the management of this malignancy and includes a
      short description of new pharmacological approaches in HCC treatment.

PMID- 19598297
TI  - Perfusion computed tomography in colorectal cancer: protocols, clinical
      applications and emerging trends.
AB  - Perfusion computed tomography (CT) has emerged as a novel functional imaging
      technique with gradually increasing importance in the management of colorectal
      cancer (CRC). By providing the functional tumor microvasculature, it also helps
      the assessment of therapeutic response of anti-angiogenic drugs as it may reflect
      tumor angiogenesis. Perfusion CT has been applied in clinical practice to
      delineate inflammatory or neoplastic lymph nodes irrespective of their size,
      identify micro-metastases and to predict metastases in advance of their
      development. It is of increasing significance for preoperative adjuvant therapies
      and avoidance of unnecessary interventions. Despite controversies regarding the
      techniques employed, its validity and reproducibility, it can be advantageous in
      the management of CRCs in which the prognosis is dependent on preoperative
      staging. With recent advances in the perfusion CT techniques, and incorporation
      to other modalities like positron emission tomography, perfusion CT will be a
      novel tool in the overall management of CRCs. This article aims at reviewing the
      existing clinical applications and recent advances of perfusion CT with a
      reference to future development in the management of CRCs.

PMID- 19598296
TI  - Characteristics of common solid liver lesions and recommendations for diagnostic
      workup.
AB  - Due to the widespread clinical use of imaging modalities such as ultrasonography,
      computed tomography and magnetic resonance imaging (MRI), previously unsuspected
      liver masses are increasingly being found in asymptomatic patients. This review
      discusses the various characteristics of the most common solid liver lesions and
      recommends a practical approach for diagnostic workup. Likely diagnoses include
      hepatocellular carcinoma (the most likely; a solid liver lesion in a cirrhotic
      liver) and hemangioma (generally presenting as a mass in a non-cirrhotic liver).
      Focal nodular hyperplasia and hepatic adenoma should be ruled out in young women.
      In 70% of cases, MRI with gadolinium differentiates between these lesions. Fine
      needle core biopsy or aspiration, or both, might be required in doubtful cases.
      If uncertainty persists as to the nature of the lesion, surgical resection is
      recommended. If the patient is known to have a primary malignancy and the lesion
      was found at tumor staging or follow up, histology is required only when the
      nature of the liver lesion is doubtful.

PMID- 19598298
TI  - Cystic echinococcosis of the liver and lung treated by radiofrequency thermal
      ablation: an ex-vivo pilot experimental study in animal models.
AB  - AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic
      echinococcosis in animal models (explanted organs). METHODS: Infected livers and
      lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts
      were photographed, and their volume, cyst content, germinal layer adhesion
      status, wall calcification and presence of daughter or adjacent cysts were
      evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80 degrees C,
      7 min. Temperature was monitored inside and outside the cyst. A second needle was
      placed inside the cyst for pressure stabilization. After treatment, all cysts
      were sectioned and examined by histology. Cysts were defined as alive if a
      preserved germinal layer at histology was evident, and as successfully treated if
      the germinal layer was necrotic. RESULTS: The subjects of the study were 17 cysts
      (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed
      100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume
      reduction of at least 65%; layer of host tissue necrosis outside the cyst, with
      average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst
      attached to the pericystium both in hepatic and lung cysts with small and focal
      de novo endocyst detachment in just 3/9 hepatic cysts. CONCLUSION: RTA appears to
      be very effective in killing hydatid cysts of explanted liver and lung. Bile duct
      and bronchial wall necrosis, persistence of endocyst attached to pericystium,
      should help avoid or greatly decrease in vivo post-treatment fistula occurrence
      and consequent overlapping complications that are common after surgery or
      percutaneous aspiration, injection and reaspiration. In vivo studies are required
      to confirm and validate this new therapeutic approach.

PMID- 19598299
TI  - Prophylaxis with carnosol attenuates liver injury induced by intestinal
      ischemia/reperfusion.
AB  - AIM: To investigate the possible protective effects of carnosol on liver injury
      induced by intestinal ischemia reperfusion (I/R). METHODS: Rats were divided
      randomly into three experimental groups: sham, intestinal I/R and carnosol
      treatment (n = 18 each). The intestinal I/R model was established by clamping the
      superior mesenteric artery for 1 h. In the carnosol treatment group, surgery was
      performed as in the intestinal I/R group, with intraperitoneal administration of
      3 mg/kg carnosol 1 h before the operation. At 2, 4 and 6 h after reperfusion,
      rats were killed and blood, intestine and liver tissue samples were obtained.
      Intestine and liver histology was investigated. Serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and interleukin (IL)-6
      were measured. Liver tissue superoxide dismutase (SOD) and myeloperoxidase (MPO)
      activity were assayed. The liver intercellular adhesion molecule-1 (ICAM-1) and
      nuclear factor kappaB (NF-kappaB) were determined by immunohistochemical analysis
      and western blot analysis. RESULTS: Intestinal I/R induced intestine and liver
      injury, characterized by histological changes, as well as a significant increase
      in serum AST and ALT levels. The activity of SOD in the liver tissue decreased
      after I/R, which was enhanced by carnosol pretreatment. In addition, compared
      with the control group, carnosol markedly reduced liver tissue MPO activity and
      serum IL-6 level, which was in parallel with the decreased level of liver ICAM-1
      and NF-kappaB expression. CONCLUSION: Our results indicate that carnosol
      pretreatment attenuates liver injury induced by intestinal I/R, attributable to
      the antioxidant effect and inhibition of the NF-kappaB pathway.

PMID- 19598300
TI  - Insulin-like growth factor binding protein-7 induces activation and
      transdifferentiation of hepatic stellate cells in vitro.
AB  - AIM: To investigate the role of insulin-like growth factor binding protein-7
      (IGFBP-7) in the activation and transdifferentiation of hepatic stellate cells
      (HSC) in vitro. METHODS: Rat HSC-T6 cells were cultured in separate dishes and
      treated with various concentration of transforming growth factor (TGF)-beta(1),
      IGFBP-7 or anti-IGFBP-7 antibody for 24 h. The supernatant or a cytoplasm
      suspension was obtained from cultured HSC, followed by transfer of cells to form
      cell-coated dishes. Immunocytochemistry and Western blotting were used to analyze
      the expression of IGFBP-7 induced by TGF-beta(1) and the level of fibronectin,
      collagen I and alpha-smooth muscle actin (SMA). The pro-apoptotic effect of anti
      IGFBP-7 antibody was determined by flow cytometry. RESULTS: Immunocytochemistry
      and Western blotting revealed that the expression of IGFBP-7 in TGF-beta(1)
      treated HSC was significantly up-regulated compared to that in the control group.
      In addition, fibronectin, collagen I and alpha-SMA also showed enhanced
      expression in accordance with the transdifferentiation process in a dose
      dependent manner to some extent. Moreover, flow cytometry suggested that anti
      IGFBP-7 antibody induced apoptosis of activated HSC, which is responsible for the
      development of liver fibrosis, and may represent a novel pathway and target for
      therapeutic intervention. CONCLUSION: IGFBP-7 showed increased expression in
      activated HSC and played an important role in the activation and
      transdifferentiation process of HSC. Anti-IGFBP-7 antibody may ameliorate liver
      fibrogenesis.

PMID- 19598301
TI  - Thermal hypersensitivity in a subset of irritable bowel syndrome patients.
AB  - AIM: To characterize thermal hypersensitivity in patients with constipation- and
      diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Thermal pain
      sensitivity was tested among patients with diarrhea-predominant IBS (D-IBS) and
      constipation-predominant IBS (C-IBS) compared to healthy subjects. A total of 42
      patients (29 female and 13 male; mean age 27.0 +/- 6.4 years) with D-IBS; 24
      patients (16 female and eight male; mean age 32.5 +/- 8.8 years) with C-IBS; and
      52 control subjects (34 female and 18 male; mean age 27.3 +/- 8.0 years)
      participated in the study. Thermal stimuli were delivered using a Medoc Thermal
      Sensory Analyzer with a 3 cm x 3 cm surface area. Heat pain threshold (HPTh) and
      heat pain tolerance (HPTo) were assessed on the left ventral forearm and left
      calf using an ascending method of limits. The Functional Bowel Disease Severity
      Index (FBDSI) was also obtained for all subjects. RESULTS: Controls were less
      sensitive than C-IBS and D-IBS (both at P < 0.001) with no differences between C
      IBS and D-IBS for HPTh and HPTo. Thermal hyperalgesia was present in both groups
      of IBS patients relative to controls, with IBS patients reporting significantly
      lower pain threshold and pain tolerance at both test sites. Cluster analysis
      revealed the presence of subgroups of IBS patients based on thermal hyperalgesia.
      One cluster (17% of the sample) showed a profile of heat pain sensitivity very
      similar to that of healthy controls; a second cluster (47% of the sample) showed
      moderate heat pain sensitivity; and a third cluster (36% of the sample) showed a
      very high degree of thermal hyperalgesia. CONCLUSION: A subset of IBS patients
      had thermal hypersensitivity compared to controls, who reported significantly
      lower HPTh and HPTo. All IBS patients had a higher score on the FBDSI than
      controls. Interestingly, the subset of IBS patients with high thermal sensitivity
      (36%) had the highest FBDSI score compared to the other two groups of IBS
      patients.

PMID- 19598302
TI  - Specific probiotics alleviate allergic rhinitis during the birch pollen season.
AB  - AIM: To investigate whether birch pollen allergy symptoms are linked with gut
      microbiota changes and whether probiotics have an effect on these. METHODS: Forty
      seven children with confirmed birch pollen allergy were randomized to receive
      either a probiotic combination of Lactobacillus acidophilus (L. acidophilus) NCFM
      (ATCC 700396) and Bifidobacterium lactis (B. lactis) Bl-04 (ATCC SD5219) or
      placebo in a double-blind manner for 4 mo, starting prior to onset of the birch
      pollen season. Symptoms were recorded in a diary. Blood samples were taken for
      analysis of cytokines and eosinophils. Fecal samples were analysed for microbiota
      components, calprotectin and IgA. Nasal swabs were taken for analysis of
      eosinophils. RESULTS: The pollen season induced a reduction in Bifidobacterium,
      Clostridium and Bacteroides which could not be prevented by the probiotic
      intervention. During the intervention, significantly higher numbers of B. lactis
      11.2 x 10(7) +/- 4.2 x 10(7) vs 0.1 x 10(7) +/- 0.1 x 10(7) bacteria/g feces (P <
      0.0001) and L. acidophilus NCFM 3.5 x 10(6) +/- 1.3 x 10(6) vs 0.2 x 10(6) +/-
      0.1 x 10(6) bacteria/g feces (P < 0.0001) were observed in the probiotic group
      compared to the placebo group. During May, there was a tendency for fewer
      subjects, (76.2% vs 95.2%, P = 0.078) to report runny nose, while during June,
      fewer subjects, 11.1% vs 33.3%, reported nasal blocking in the probiotics group
      (P = 0.101). Concomitantly, fewer subjects in the probiotic group had
      infiltration of eosinophils in the nasal mucosa compared to the placebo group,
      57.1% vs 95% (P = 0.013). Eye symptoms tended to be slightly more frequent in the
      probiotic group, 12.5 d [interquartile range (IQR) 6-18] vs 7.5 d (IQR 0-11.5) (P
      = 0.066) during May. Fecal IgA was increased in the placebo group during the
      pollen season; this increase was prevented by the probiotics (P = 0.028).
      CONCLUSION: Birch pollen allergy was shown to be associated with changes in fecal
      microbiota composition. The specific combination of probiotics used was shown to
      prevent the pollen-induced infiltration of eosinophils into the nasal mucosa, and
      indicated a trend for reduced nasal symptoms.

PMID- 19598303
TI  - Color Doppler sonography and angioscintigraphy in hepatic Hodgkin's lymphoma.
AB  - AIM: To estimate the characteristics of Color Doppler findings and the results of
      hepatic radionuclide angiography (HRA) in secondary Hodgkin's hepatic lymphoma.
      METHODS: The research included patients with a diagnosis of Hodgkin's lymphoma
      with metastatic focal lesions in the liver and controls. Morphologic
      characteristics of focal liver lesions and hemodynamic parameters were examined
      by pulsed and Color Doppler in the portal, hepatic and splenic veins were
      examined. Hepatic perfusion index (HPI) estimated by HRA was calculated. RESULTS:
      In the majority of patients, hepatomegaly was observed. Lesions were mostly
      hypoechoic and mixed, solitary or multiple. Some of the patients presented with
      dilated splenic veins and hepatofugal blood flow. A pulse wave was registered in
      the centre and at the margins of lymphoma. The average velocity of the pulse wave
      was higher at the margins (P > 0.05). A continuous venous wave was found only at
      the margins of lymphoma. There was no linear correlation between lymphoma size
      and velocity of pulse and continuous wave (r = 390, P < 0.01). HPI was
      significantly lower in patients with lymphomas than in controls (P < 0.05),
      pointing out increased arterial perfusion in comparison to portal perfusion.
      CONCLUSION: Color Doppler ultrasonography is a sensitive method for the detection
      of neovascularization in Hodgkin's hepatic lymphoma and estimation of its
      intensity. Hepatic radionuclide angiography can additionally help in the
      assessment of vascularisation of liver lesions.

PMID- 19598304
TI  - Impact of fecal incontinence on quality of life.
AB  - AIM: To explore the impact of fecal incontinence (FI) on quality of life (QOL) of
      patients attending urogynecology and colorectal clinics (CCs). METHODS: Cross
      sectional study of 154 patients (27 male) with FI, who attended the clinics at a
      regional hospital in North Queensland, Australia in 2003 and 2004, and completed
      the Fecal Incontinence Quality of Life Scale (FIQL: 1 = very affected; 4 = not
      affected). RESULTS: More than 22% of patients had their QOL affected severely by
      FI. Patients reported that they had not previously been asked about FI by a
      medical practitioner nor did they voluntarily disclose its presence. The median
      FIQL scores for all participants were: lifestyle = 3.24; coping = 2.23;
      depression = 2.42; and embarrassment = 2.33. Increasing frequency of soiling had
      a negative effect on all four FIQL scales (P < 0.001) as did the quantity of
      soiling (P < 0.01). Female CC patients had poorer FIQL scores than urogynecology
      clinic patients for lifestyle (P = 0.015), coping (P = 0.004) and embarrassment
      (P = 0.009), but not depression (P = 0.062), despite having experienced FI for a
      shorter period. CONCLUSION: Failure to seek treatment for FI degrades the quality
      of patients' lives over time. FI assessment tools should incorporate the quantity
      of fecal loss.

PMID- 19598306
TI  - Psychometrics of the chronic liver disease questionnaire for Southern Chinese
      patients with chronic hepatitis B virus infection.
AB  - AIM: To test the psychometric properties of a Chinese [(Hong Kong) HK]
      translation of the chronic liver disease questionnaire (CLDQ). METHODS: A Chinese
      (HK) translation of the CLDQ was developed by iterative translation and cognitive
      debriefing. It was then administered to 72 uncomplicated and 78 complicated
      chronic hepatitis B (CHB) patients in Hong Kong together with a structured
      questionnaire on service utilization, and the Chinese (HK) SF-36 Health Survey
      Version 2 (SF-36v2). RESULTS: Scaling success was > or = 80% for all but three
      items. A new factor assessing sleep was found and items of two (Fatigue and
      Systemic Symptoms) subscales tended to load on the same factor. Internal
      consistency and test-retest reliabilities ranged from 0.58-0.90 for different
      subscales. Construct validity was confirmed by the expected correlations between
      the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly
      lower in complicated compared with uncomplicated CHB, supporting sensitivity in
      detecting differences between groups. CONCLUSION: The Chinese (HK) CLDQ is valid,
      reliable and sensitive for patients with CHB. Some modifications to the scaling
      structure might further improve its psychometric properties.

PMID- 19598305
TI  - Is ERCP really necessary in case of suspected spontaneous passage of bile duct
      stones?
AB  - AIM: To investigate the usefulness of magnetic resonance cholangiopancreatography
      (MRCP) and the need for endoscopic retrograde cholangiopancreatography (ERCP) in
      cases of suspected spontaneous passage of stones into the common bile duct.
      METHODS: Thirty-six patients with gallbladder stones were clinically suspected of
      spontaneous passage of stones into the common bile duct because they presented
      with clinical symptoms such as abdominal pain and fever, and showed signs of
      inflammatory reaction and marked rise of hepatobiliary enzymes. These symptoms
      resolved and they showed normalized values of blood biochemical parameters after
      conservative treatment without evidence of stones in the common bile duct on
      MRCP. All these patients were subjected to ERCP within 3 d of MRCP to check for
      the presence of stones. RESULTS: No stones were detected by ERCP in any patient,
      confirming the results of MRCP. CONCLUSION: When clinical symptoms improve, blood
      biochemical parameters have normalized, and MRCP shows there are no stones in the
      common bile duct, it can be considered the stone has spontaneously passed and
      thus ERCP is not necessary.

PMID- 19598307
TI  - Liver and spleen volume variations in patients with hepatic fibrosis.
AB  - AIM: To study the liver and spleen volume variations in hepatic fibrosis patients
      at different histopathological stages. METHODS: Multidetector computed tomography
      (MDCT) scan was performed in 85 hepatic fibrosis patients. Liver volume (LV) and
      spleen volume (SV) were measured. Fifteen healthy individuals served as a control
      group (S0). The patients were divided into stage 1 (S1) group (n = 34), stage 2
      (S2) group (n = 25), stage 3 (S3) group (n = 16), and stage 4 (S4) group (n = 10)
      according to their histopathological stage of liver fibrosis. RESULTS: The LV and
      standard LV(SLV)had a tendency to increase with the severity of fibrosis, but no
      statistical difference was observed in the 5 groups (LV: F = 0.245, P = 0.912;
      SLV: F = 1.902, P = 0.116). The SV was gradually increased with the severity of
      fibrosis, and a statistically significant difference in SV was observed among the
      5 groups (P < 0.01). The LV/SV ratio and SLV/SV ratio were gradually decreased
      with the aggravation of hepatic fibrosis, and statistically significant
      differences in both LV/SV and SLV/SV were found among the 5 groups (P < 0.01).
      CONCLUSION: The absence of obvious LV reduction in patients with chronic liver
      disease may be a morphological index of patients without liver cirrhosis. The SV
      is related to the severity of fibrosis, and the spleen of patients with advanced
      fibrosis is enlarged evidently. The LV/SV ratio and SLV/SV ratio are of a
      significant clinical value in the diagnosis of advanced liver fibrosis.

PMID- 19598308
TI  - Adult intussusception: a retrospective review of 41 cases.
AB  - AIM: To optimize the preoperative diagnosis and surgical management of adult
      intussusception (AI). METHODS: A retrospective review of the clinical features,
      diagnosis, management and pathology 41 adult patients with postoperative
      diagnoses of intussusception was conducted. RESULTS: Forty-one patients with 44
      intussusceptions were operated on, 24.4% had acute symptoms, 24.4% had subacute
      symptoms, and 51.2% had chronic symptoms. 70.7% of the patients presented with
      intestinal obstruction. There were 20 enteric, 15 ileocolic, eight colocolonic
      and one sigmoidorectal intussusceptions. 65.9% of intussusceptions were diagnosed
      preoperatively using a computed tomography (CT) scan (90.5% accurate) and
      ultrasonography (60.0% accurate, rising to 91.7% for patients who had a palpable
      abdominal mass). Coloscopy located the occupying lesions of the lead point of
      ileocolic, colocolonic and sigmoidorectal intussusceptions. Four intussusceptions
      in three patients were simply reduced. Twenty-one patients underwent resection
      after primary reduction. There was no mortality and anastomosis leakage
      perioperatively. Except for one patient with multiple small bowel adenomas, which
      recurred 5 mo after surgery, no patients were recurrent within 6 mo.
      Pathologically, 54.5% of the intussusceptions had a tumor, of which 27.3% were
      malignant. 9.1% comprised nontumorous polyps. Four intussusceptions had a
      gastrojejunostomy with intestinal intubation, and four intussusceptions had no
      organic lesion. CONCLUSION: CT is the most effective and accurate diagnostic
      technique. Colonoscopy can detect most lead point lesions of non-enteric
      intussusceptions. Intestinal intubation should be avoided.

PMID- 19598309
TI  - Unexplainable development of a hydatid cyst.
AB  - Echinococcosis is a cyclozoonosis characterized by cystic lesions usually
      situated inside or outside the liver. We discuss the case of a 77-year-old woman
      with a recurrent hydatidosis with a cyst arising from the liver, growing through
      the lateral right abdomen wall, and reaching the subcutaneous tissue of the
      lumbar region. In the literature, rare subcutaneous or muscular localizations of
      hydatid cysts are described, however, there is no mention of a cyst growing over
      the abdominal wall muscles, shaped like an hourglass, partially in the liver and
      partially in the subcutaneous tissue, as in our case. We have not found any
      pathogenetic explanation for this growth pattern which is not typical of the
      biological behaviour of a hydatid cyst.

PMID- 19598310
TI  - Excision of a large abdominal wall lipoma improved bowel passage in a Proteus
      syndrome patient.
AB  - Proteus syndrome is an extremely rare congenital disorder that produces
      multifocal overgrowth of tissue. This report presents a surgical case of a large
      lipoma in the abdominal wall of a patient with Proteus syndrome. She was
      diagnosed with Proteus syndrome based on certain diagnostic criteria. The
      neoplasm increased in size gradually, producing hemihypertrophy of her left lower
      extremity and trunk, and spread to her retroperitoneum and her left abdominal
      wall. She experienced gradually progressive constipation, nausea, vomiting, and
      abdominal pain. Computed tomography (CT) of the abdomen demonstrated a large mass
      in the subcutaneous adipose tissue of the left lower abdominal wall which
      measured 12 cm x 8 cm x 6 cm in diameter and encased the left colon. This mass in
      the abdominal wall was excised. The weight of the excised mass was 1550 g. The
      histopathological diagnosis of this mass was lipoma. After surgery, the
      encasement of the left colon was improved, and the patient was able to move her
      bowels twice per day. The excision of the large lipoma in the abdominal wall
      contributed to the improved bowel passage in this patient with Proteus syndrome.

PMID- 19598312
TI  - Large cavernous hemangioma in the cecum treated by laparoscopic ileocecal
      resection.
AB  - A cavernous hemangioma of the cecum is a rare vascular malformation but is
      clinically important because of the possibility of massive bleeding. We report a
      case of a large cavernous hemangioma with pericolic infiltration in the cecum
      which was removed successfully using minimally invasive surgery.

PMID- 19598311
TI  - Granular cell tumor of the cecum with extensive hyalinization and calcification:
      a case report.
AB  - A granular cell tumor (GCT) is a benign neoplasm of unclear histogenesis that is
      generally believed to be of nerve sheath origin. GCT is not common and most often
      affects the tongue, skin and soft tissue, although it may occur anywhere in the
      body. We experienced a case of GCT that arose in the cecum of a 55-year-old man.
      The GCT was removed by laparoscopic resection. In addition to the tumor,
      endoscopic examination revealed the presence of a 5-mm-polyp in the descending
      colon and multiple tiny polyps in the sigmoid colon and rectum. Histological
      examination demonstrated a cecal tumor 1.5 cm x 1.0 cm x 0.7 cm with a hard
      consistency; in cut sections, mixed cells with yellowish and whitish portions
      were seen. The tumor was located between the mucosa and subserosa, and was
      composed of plump histiocyte-like tumor cells with abundant granular eosinophilic
      cytoplasm, which were immunoreactive for S-100 protein, vimentin, neuron-specific
      enolase, inhibin-alpha and calretinin. The tumor showed extensive hyalinization
      and focal dystrophic calcification. Immunohistochemical profiles did not confirm
      any particular cell type for the histogenetic origin of the GCT, including a
      nerve sheath origin. Extensive hyalinization and calcification showing involution
      of tumor cells suggest benign clinical behavior of GCT.

PMID- 19598313
TI  - Different modalities of arterial reconstruction in hepatic retransplantation
      using right partial graft.
AB  - Though split-liver and living-related transplantation are routinely performed,
      they are done almost exclusively for primary liver transplantation because of
      potential surgical difficulties. These difficulties are generally related to
      arterial revascularization, particularly if there is hepatic artery thrombosis.
      According to UNOS data, of the hepatic retransplantations performed between 1996
      and 2007, only 8.7% were done using right or extended right grafts from deceased
      donors, and 14.3% using right grafts from live donors. Here we report our
      experience with 5 hepatic retransplantations in which right partial grafts
      resulting from conventional in situ splits, and one right lobe resulting from an
      adult-to-adult living-related transplant, were successfully used with different
      modalities of graft arterialization.

PMID- 19598314
TI  - Fingertip replantations: importance of venous anastomosis and the clinical
      results.
AB  - Overall survival rate for 143 digits with complete amputation of the distal
      phalanx was 78%. Replanted digits that underwent venous anastomosis showed a very
      high survival rate of 93%. Loss of the distal interphalangeal joint function in
      subzone IV was significantly inferior to that in subzones II and III. Protective
      sensation was achieved in 96% of replanted digits. Sensory recovery in the
      absence of nerve repair was significantly worse for avulsion injury than for
      crush injury. Nail deformity tended to be increased for replanted digits in
      subzone III or with crush-type injury. Successful venous anastomosis appears to
      offer the best way to promote survival of replanted digits. If venous anastomosis
      is infeasible, a replanted digit can survive with any methods for venous drainage
      in subzones II and III, but does not survive in subzone IV. To minimise nail
      deformity, repair of the germinal matrix is necessary.

PMID- 19598315
TI  - Mycobacterium chelonae hand infection: a review.
AB  - Six cases of culture-proven Mycobacterium chelonae tenosynovitis were identified
      through retrospective chart review. Fifteen cases were identified using
      computerised Medline search. Clinical features, treatment and outcome were
      described. Infection control was achieved in our patients with an average of 3.2
      surgeries each and antibiotic treatment for six months to one year. Eleven
      published cases were managed by combined surgery and systemic antibiotics, with
      an average of 1.73 surgeries per patient and seven weeks to 24 months of
      antibiotics. All our patients were disease free on final follow-up. Thirteen
      cases were resolved. Functional outcomes were reported for eight cases.
      Comparison of functional outcome was not possible because different parameters
      were used in different reports. Aggressive debridement, susceptibility-guided
      antibiotics, and supervised rehabilitation resulted in infection control and
      acceptable hand function for our patients. Standardised data collection on
      subsequent cases would facilitate outcome monitoring and formulation of a
      treatment guideline for this disease.

PMID- 19598317
TI  - Simultaneous metacarpophalangeal joint ulnar collateral ligament injury and
      carpometacarpal dislocation of the thumb in a football player: a case report.
AB  - An unusual case of ulnar collateral ligament avulsion in association with
      carpometacarpal dislocation of thumb is described. Symptoms and deformity caused
      by dislocation can mask the presence of injuries such as damage to the ulnar
      collateral ligament of thumb. This may lead to long term disability. A high index
      of suspicion and good clinical examination allows correct diagnosis and
      management of these uncommon injuries leading to a good clinical outcome.

PMID- 19598316
TI  - Radiolunate fusion with distraction using corticocancellous bone graft for
      minimizing decrease of wrist motion in rheumatoid wrists.
AB  - Radiolunate fusion is a limited carpal fusion procedure used for patients with
      rheumatoid arthritis. However, this procedure inevitably causes decreases in
      range of motion, especially wrist flexion. Linscheid and Dobyns described the
      possibility of minimizing the decrease in motion at the radiocarpal joint by
      slight distraction of the joint. We hypothesized for our modified procedure that
      a corticocancellous bone graft was inserted between the radius and the lunate
      with a small amount of over-correction could provide slight distraction of
      radioscaphoid joint and protect the joint from decreased range of motion after
      arthrodesis. Twelve wrists in ten patients with rheumatoid arthritis underwent
      radiolunate fusion. Mean age at operation was 53 years old and mean follow-up
      period was 5.7 years. Clinical evaluation and radiological assessment showed that
      decrease in range of motion was minimized compared with other procedures. Because
      our modified procedure can minimize decrease in motion, it is recommended.

PMID- 19598318
TI  - Revision metacarpophalangeal joint replacement 30 years after primary swanson
      flexible silicone implant arthroplasty in a rheumatoid patient: a case report.
AB  - We report a case of a patient with rheumatoid arthritis undergoing revision
      surgery 30 years after primary metacarpophalangeal joint arthroplasty using a
      Swanson implant. Removal and replacement of the implant were successfully
      performed, and the patient was satisfied with the revision surgery.

PMID- 19598319
TI  - In situ rotational dislocation of the trapezoid associated with carpal-metacarpal
      dislocations.
AB  - A rare case of in situ rotational dislocation of the trapezoid was described
      after dislocation of the index and long carpal-metacarpal joints. Due to the
      difficulty in visualising the trapezoid on plain radiographs, there was a delay
      in assessing the full extent of the injury. However, after further imaging, the
      case required open reduction and internal fixation. Therefore, in cases involving
      high energy dislocations of the second and third metacarpal CMC joints, injury to
      the peri-trapezoid ligaments should be considered. A pre-operative CT scan or, if
      not available, open fixation of the CMC joints and trapezoid, is recommended.

PMID- 19598320
TI  - Flexor digitorum profundus tendon rupture associated with distal radius fracture
      malunion: a case report.
AB  - We present a case of subcutaneous flexor tendon rupture of the index finger
      following malunion of a distal radius fracture. The cause of the tendon rupture
      was mechanical attrition due to a bony prominence at the palmar joint rim in the
      distal radius due to malunion. Corrective osteotomy and the Sauve-Kapandji
      procedure were carried out for the wrist pain and forearm rotation disability and
      a tendon graft was carried out for the flexor tendon rupture. Recovery was
      satisfactory.

PMID- 19598321
TI  - Irreducible simultaneous dislocation of both interphalangeal joints in the little
      finger: a case report.
AB  - We present a case with irreducible simultaneous dislocation of both the distal
      interphalangeal (DIP) and proximal interphalangeal (PIP) joints in the little
      finger. A combination of the delay from injury to closed reduction and the
      entrapped flexor digitorum profundus (FDP) tendon at the PIP joint prevented
      closed reduction from being performed. To our knowledge, this is the first report
      of such a condition.

PMID- 19598322
TI  - De Quervain disease caused by abductor pollicis longus tenosynovitis: a report of
      three cases.
AB  - De Quervain disease is caused by a stenosing tenosynovitis in the first dorsal
      compartment, and the main aetiology is extensor pollicis brevis (EPB)
      tenosynovitis. We encountered three cases in which EPB tenosynovitis was absent
      and abductor pollicis longus (APL) tenosynovitis was confirmed during operation.
      In the treatment of de Quervain disease, APL tenosynovitis should be paid as much
      attention as EPB tenosynovitis.

PMID- 19598323
TI  - Ulnar-sided wrist pain after four-corner fusion in a previously-asymptomatic
      ulnar positive wrist: a case report.
AB  - Scaphoid excision and four-corner fusion is one of the treatment choices for
      patients who have stage II or III SLAC (scapholunate advanced collapse)/SNAC
      (scaphoid non-union advanced collapse) wrist arthritis. We report a case of ulnar
      sided wrist pain which occurred after four-corner fusion for stage II SNAC wrist
      with a previously-asymptomatic ulnar positive variance, and was successfully
      treated by ulnar shortening osteotomy. This case highlights a possible
      coincidental pathology of the ulnocarpal joint in the setting of post-traumatic
      radiocarpal arthrosis.

PMID- 19598324
TI  - A case of venous varix of the volar digit and review of the literature.
AB  - Venous varix of the volar digit (VVVD) is a rare condition that is usually
      described as a firm, blue, and painful mass. However, the clinical features of
      VVVD are still unclear. We treated a patient who had a firm, normal-skin-colored,
      and painless mass on the volar aspect of a digit. The mass was removed and was
      diagnosed as VVVD by histological examination. Magnetic resonance imaging was
      useful for assisting with the pre-operative diagnosis. We also review 11
      previously reported cases.

PMID- 19598325
TI  - Closing radial wedge osteotomy for Preiser's combined with Kienbock's disease:
      two case reports.
AB  - Avascular necrosis involving more than one carpal bone is rare, and the
      appropriate treatment for this condition has not yet been established. In this
      report, two patients with concomitant Preiser's and Kienbock's disease who also
      had severe wrist pain without obvious traumas were treated by closing radial
      wedge osteotomy (CRWO). Clinical evaluation showed that CRWO was effective
      against both conditions and indicated that it is more suitable for early stage
      than stage II diseases of the Hebert and Lichtman classifications.

PMID- 19598327
TI  - Dupuytren's disease confined to the interphalangeal joints: a case report.
AB  - A typical case of Dupuytren's contracture confined to the interphalangeal joints
      of the right little finger, occurred in a 79-year-old man. No past history of
      risk factors or family history of Dupuytren's disease could be detected.
      Excisions of the abnormal cords lead to good clinical outcome.

PMID- 19598326
TI  - A Blauth IIIB hypoplastic thumb reconstructed with a vascularised metatarso
      phalangeal joint transfer: a case report with 28 years of follow up.
AB  - We reconstructed the Blauth-IIIB hypoplastic right thumb of a 16-year-old girl
      with a vascularised metatarso-phalangeal (MTP) joint from her second toe combined
      with a dorsalis-pedis flap. Abduction was provided with an abductor policis long
      tendon advancement, and adduction, with an extensor indicis proprius tendon
      transfer. Opponoplasty was performed one year later using the flexor sublimis
      (IV) tendon. The transferred joint remained functional and non-osteoarthritic 28
      years later. Radial and palmar abduction of the reconstructed thumb was 45
      degrees and 75 degrees respectively. The index, middle, and ring fingers could
      oppose the thumb, however she grasped small objects between her index and middle
      fingertips. If a pollicisation using the index finger is not accepted, the
      reconstruction described here is one of the surgical options. However donor-foot
      morbidity is not negligible. Currently, we use a proximal-interphalangeal joint
      transfer with an opponoplasty using an abductor digiti minimi as a first choice,
      when planning a reconstruction of preserved hypoplasic thumb.

PMID- 19598329
TI  - Colonic adenoma patients have higher incidence of  hyperplastic polyps on
      surveillance colonoscopy.
AB  - OBJECTIVES: To determine the incidence of hyperplastic polyps in patients
      undergoing surveillance colonoscopy and to compare with the prevalence in
      individuals undergoing index colonoscopy. PATIENTS AND METHODS: This prospective
      observational study included patients with index colonoscopy findings of
      adenomas, adenoma with concomitant hyperplastic polyps and advanced neoplasia who
      subsequently underwent surveillance colonoscopy. Patient characteristics,
      indications for colonoscopy, interval between examinations and findings were
      recorded. These findings were compared with our control group that comprised of
      patients who underwent index colonoscopy during the same period. RESULTS: Study
      group consisted of 108 patients (median age 61.5 years) who underwent index
      colonoscopy for indications including, weight loss, rectal bleeding, altered
      bowel habits and anaemia. On index colonoscopy, adenomas, adenoma with
      concomitant hyperplastic polyps and advanced neoplasia were present in 61, 35 and
      12 patients, respectively. Surveillance colonoscopy was performed after a mean
      follow-up period of 29 +/- 17 months. Findings on surveillance examination
      included hyperplastic polyps in 35 and 57% of patients with past adenomas and
      adenoma with concomitant hyperplastic polyps, respectively. Control group
      included 3852 symptomatic patients who had index colonoscopy (median age, 65
      years). Hyperplastic polyps, adenomas and advanced neoplasia were found in 155
      (4%), 388 (10%) and 60 (1.5%) of patients, respectively. Hyperplastic polyps and
      adenoma were significantly higher in study group as compared with control group
      (P >0.5). CONCLUSION: Incidence of hyperplastic polyps is significantly higher on
      surveillance colonoscopy as compared with the prevalence on index colonoscopy.
      This may signify a continuous spectrum of biological evolution between
      hyperplastic polyps and adenomas.

PMID- 19598328
TI  - Endoscopic surveillance for Barrett's oesophagus: the patients' perspective.
AB  - OBJECTIVE: Barrett's oesophagus (BO) is associated with the development of
      oesophageal adenocarcinoma and endoscopic surveillance is commonly practised. In
      view of the clinical, psychological and economic implications of BO, we have
      studied patients' attitudes towards surveillance, their levels of anxiety and
      quality of life. METHODS: Patients with BO undergoing endoscopic surveillance
      were asked to complete a questionnaire,including seven questions on their
      experience of surveillance, the Hospital Anxiety and Depression Scale,the Trust
      in Physician Scale (TIPS) and the Short Form-36 quality of life questionnaire.
      RESULTS: Of the 250 patients invited, 178 responded (71%).One hundred and fifty
      one (60%) completed the questionnaire sufficiently for analysis [median age 66
      (range 41-79) years, 101 male]. Twenty-nine percent of patients had received too
      little information concerning surveillance of BO and 22% no information at all.
      Information was deemed difficult to understand by 24%. Hospital Anxiety and
      Depression Scale anxiety score: 14%abnormal, 25% borderline. Quality of life was
      lower than the general population in seven of eight Short Form-36 parameters.
      Increasing TIPS score correlated with having received (r= 0.33, P <0.001) and
      understood (r = 0.2, P= 0.037) BO information, and negatively with the belief
      that endoscopic surveillance reduced oesophageal adenocarcinoma risk (r= - 0.19,
      P =0.025). Increasing TIPS score was associated with less anxiety (P= 0.015) and
      depression (P =0.001), and better quality of life. CONCLUSION: Patients
      undergoing endoscopic surveillance for BO suffer anxiety and have impaired
      quality of life. As trust in their physicians is correlated with receiving
      sufficient BO information, we surmise that ensuring BO patients understand their
      condition is likely to improve quality of life, anxiety and depression.

PMID- 19598330
TI  - Gallbladder wall variceal haemorrhage with associated  rupture: a rare cause of
      mortality in the cirrhotic patient.
AB  - Gallbladder wall varices are unusual ectopic varices, which occur in the setting
      of portal hypertension, usually but not universally associated with portal vein
      thrombosis. Rupture of these varices may lead to life-threatening intra abdominal
      haemorrhage and is associated with a high mortality rate. We report a case of
      gallbladder wall variceal haemorrhage in a cirrhotic patient with patent
      transjugular intrahepatic portosystemic shunt, which resulted in death.

PMID- 19598331
TI  - Findings of scientific misconduct.

PMID- 19598332
TI  - Findings of scientific misconduct.

PMID- 19598333
TI  - Women have increased rates of cartilage loss and progression of cartilage defects
      at the knee than men: a gender study of adults without clinical knee
      osteoarthritis.
AB  - OBJECTIVE: Women have an increased risk of knee osteoarthritis (OA). However,
      little is known about gender differences in cartilage health before the onset of
      clinical knee OA. The aim of this study was to examine whether there are
      longitudinal gender differences in knee cartilage in a cohort of healthy,
      asymptomatic adults with no clinical knee disease. METHODS: Two hundred seventy
      one participants (169 women) aged between 50 and 79 years with no clinical
      history of knee pain or pathology were examined using magnetic resonance imaging
      at baseline and 2.3 years later. From these images, changes in tibial and patella
      cartilage volume and progression of cartilage defects were determined. RESULTS:
      In multivariate analyses, after adjustment for potential confounders, the average
      annual percentage loss of total tibial cartilage volume was significantly greater
      in women (1.6% [95% CI, 1.1-2.2]) than in men (0.4%[95% CI, -0.4 to 1.2]) (P =
      0.05 for difference). Likewise, the female gender was also associated with an
      increased risk for the progression of tibiofemoral cartilage defects (odds ratio,
      3.0; 95% CI, 1.1-8.1; P = 0.03). At the patella,the average annual percentage
      loss of cartilage volume was significantly greater in women (2.3% [95% CI, 1.7
      2.8]) than in men (0.8% [95% CI, 0.1-1.6]) (P = 0.02 for difference).
      CONCLUSIONS: The female predisposition toward knee OA may, at least in part, be
      due to gender differences in cartilage health, even before the onset of clinical
      knee disease. Understanding the mechanism for these gender differences may
      provide a means to reduce the risk of knee OA in women.

PMID- 19598334
TI  - [A new method to obtain right-to-left shunt index of the lung using 99mTc-MAA
      pulmonary perfusion scintigraphy and first-pass dynamic data acquisition].
AB  - Generally a right-to-left shunt index in pulmonary area was calculated from total
      body and pulmonary area by scintillations count using 9mTc-MAA pulmonary
      perfusion scintigraphy. In this study, we devised a newly calculation method for
      right-to-left shunt index in pulmonary area from 9mTc-MAA pulmonary perfusion
      scintigraphy by first-pass dynamic data. We compared the proposed method with the
      conventional method in 26 patients (9 men and 17 women; 3-26 years old): 23
      patients with congenital biliary atresia (CBA) post operation and the other 3
      patients with right-to-left shunt from hepatopulmonary syndrome. As a result,
      there was a positive correlation of the index values between the proposed method
      and the conventional method (r = 0.929). Thus, the present method should be
      clinically useful.

PMID- 19598335
TI  - The intersection of psychiatric diagnosis and inherited metabolic disease.

PMID- 19598336
TI  - Prospective Randomized Study of Marsupialization versus Silver Nitrate
      Application in the Management of Bartholin Gland Cysts and Abscesses.
AB  - STUDY OBJECTIVE: To prospectively compare the efficacy of marsupialization or
      silver nitrate application in the treatment of Bartholin gland cysts abscesses,
      both of which are widely used as outpatient procedures. DESIGN: Prospective
      randomized trial. Design classification I. SETTING: Teaching and research
      hospital, a tertiary center. PATIENTS: A total of 212 patients admitted to our
      gynecology clinic with symptomatic Bartholin gland cysts/abscesses.
      INTERVENTIONS: Marsupialization and silver nitrate application in Bartholin gland
      cysts/abscesses. MEASUREMENTS AND MAIN RESULTS: In all, the 212 patients were
      randomly allocated to either marsupialization (group I) or silver nitrate
      application (group II) from March 2005 through March 2007. A total of 159 women
      were eligible for reevaluation at the end of the sixth month. In all, 83 were
      randomized to group I and 76 to group II. The patients were called for revisits
      at day 3, day 7, month 1, and month 6 of treatment. The 2 groups were compared
      for recurrence rates as primary outcome and duration of procedures,
      complications, size of scar tissues, and presence of dyspareunia as secondary
      outcomes. Comparisons of 2 groups were evaluated by Pearson X(2) test and Mann
      Whitney U test, as appropriate. The 2 groups were comparable with regard to age,
      parity, and diameter of cyst or abscess. The recurrence rates were similar: 24.1%
      in group I and 26.3% in group II at 6 months (p =.67). No statistically
      significant differences were found in respect to duration of procedures or
      presence of dyspareunia. Complete healing without scar formation was observed in
      31.3% and 55.7% of patients in groups I and II, respectively, and this was
      statistically significant (p =.007). CONCLUSION: Marsupialization and silver
      nitrate application seem to be equally effective management methods in Bartholin
      cyst and abscesses, however, silver nitrate favors complete healing with less
      scar formation.

PMID- 19598337
TI  - Editorial: a handle with care.

PMID- 19598338
TI  - Monitoring of the ambulatory patient under general anesthesia.

PMID- 19598339
TI  - Indications for endotracheal intubation and a practical technique.

PMID- 19598340
TI  - Presidential perceptions.

PMID- 19598342
TI  - Correction: component roll call.

PMID- 19598341
TI  - The psychological preparation of the child for dental surgery (part I).

PMID- 19598343
TI  - A moscow experience with intravenous amnesia.

PMID- 19598345
TI  - From precedent to doctrine.

PMID- 19598344
TI  - Fear of a child.

PMID- 19598346
TI  - First anesthesia site made national shrine.

PMID- 19598347
TI  - U.s. Government release.

PMID- 19598348
TI  - Dr. Timmons Heads "AFDE Month".

PMID- 19598349
TI  - Hospital de occidente.

PMID- 19598350
TI  - Drug warning.

PMID- 19598351
TI  - Evaluating your office: resuscitation program.

PMID- 19598352
TI  - Letter to the editor.

PMID- 19598353
TI  - Editorial: "doctor evaluation".

PMID- 19598354
TI  - Case report: facial anesthesia and paralysis due to intra-arterial injection of
      local anesthesia.

PMID- 19598355
TI  - Necrology.

PMID- 19598356
TI  - Public health for the public good.

PMID- 19598357
TI  - President's Report.

PMID- 19598358
TI  - Patient management-psychologic.

PMID- 19598359
TI  - Summation.

PMID- 19598360
TI  - Blood pressure monitoring-new device.

PMID- 19598361
TI  - Intravenous sedation.

PMID- 19598363
TI  - Guest editorial: "the common goal".

PMID- 19598362
TI  - Pain control: trigeminal neuralgia-a review of etiology and treatment.

PMID- 19598364
TI  - "In defence of controversy".

PMID- 19598365
TI  - Guest Editorial: "... for and by".

PMID- 19598366
TI  - Will it Hurt?

PMID- 19598368
TI  - What's Needed?

PMID- 19598367
TI  - Office physical evaluation.

PMID- 19598372
TI  - Tell It How It is.

PMID- 19598371
TI  - The dental student: 1987.

PMID- 19598369
TI  - Tranquilizers and anesthesia.

PMID- 19598370
TI  - Current concepts: shock.

PMID- 19598373
TI  - Dear dr. Greenfield.

PMID- 19598374
TI  - Emergency airway, ventilation, and cardiac resuscitation.

PMID- 19598376
TI  - Eight months after anesthesiology residency.

PMID- 19598375
TI  - Loma linda plans for new anesthesia chief.

PMID- 19598377
TI  - Thank you-dick weaver.

PMID- 19598378
TI  - "On General Anesthesia"-revisited.

PMID- 19598379
TI  - "On General Anesthesia"-revisited.

PMID- 19598380
TI  - "On General Anesthesia"-revisited.

PMID- 19598381
TI  - "On General Anesthesia"-revisited.

PMID- 19598382
TI  - ... And rebuttal.

PMID- 19598384
TI  - Stability of brevital sodium.

PMID- 19598383
TI  - Letter to the editor.

PMID- 19598385
TI  - Incremental brevital.

PMID- 19598386
TI  - Joint commission bulletin.

PMID- 19598387
TI  - U.s. Department of health, education and welfare.

PMID- 19598389
TI  - British association of oral surgeons.

PMID- 19598388
TI  - A muscle relaxant causes respiratory sequellae.

PMID- 19598390
TI  - Methoxyflurane and renal toxicity.

PMID- 19598392
TI  - Hypnosis called effective for dentally handicapped.

PMID- 19598391
TI  - Re: joint commission bulletin.

PMID- 19598394
TI  - Medicaid as it relates to the limited practice of restorative dentistry under
      general anesthesia.

PMID- 19598393
TI  - Use and abuse of antibiotics.

PMID- 19598396
TI  - U.s. Department of health, education and welfare.

PMID- 19598398
TI  - American fund for dental education.

PMID- 19598399
TI  - "The Jorgensen Technique"-a Tribute to Neils Bjorn Jorgensen.

PMID- 19598402
TI  - American Society of Oral Surgeons - President's Message.

PMID- 19598403
TI  - Correspondence... And reply.

PMID- 19598407
TI  - Evaluation of levoprome and demerol as pre-operative medications.

PMID- 19598411
TI  - Gentlemen This is no Humbug!

PMID- 19598412
TI  - Alert.

PMID- 19598410
TI  - Letters to the editor.

PMID- 19598413
TI  - The enigma of air dilution.

PMID- 19598414
TI  - The use and effects of general anesthetic agents on patients with pre-existing
      diseases.

PMID- 19598415
TI  - Hidden Hazards of the McKesson Narmatic Anesthesia Machine.

PMID- 19598416
TI  - Battle of britain.

PMID- 19598417
TI  - Amnesia-analgesia for special-care patients: a technique of intravenous sedation
      and supplemental analgesia.

PMID- 19598418
TI  - Phenol neurolysis as an alternative to avulsion of the mandibular nerve: a case
      report.

PMID- 19598419
TI  - Profile-william R. Wallace, second vice president.

PMID- 19598420
TI  - Why not change?

PMID- 19598421
TI  - Letters to the editor.

PMID- 19598422
TI  - Comments on the total spectrum of pain control in dentistry.

PMID- 19598423
TI  - Letters to the editor.

PMID- 19598424
TI  - Letter to the editor.

PMID- 19598425
TI  - Letter to the editor.

PMID- 19598426
TI  - A think-pause.

PMID- 19598428
TI  - Letter to the editor.

PMID- 19598427
TI  - Pain and Prejudice: Why do we doubt that the patient is in pain?

PMID- 19598429
TI  - Dental anesthesia institute.

PMID- 19598430
TI  - On conceptual growth.

PMID- 19598432
TI  - Acupuncture and dentistry.

PMID- 19598433
TI  - Letters to the editor.

PMID- 19598431
TI  - Educating for pain control.

PMID- 19598434
TI  - Halothane-legal action.

PMID- 19598435
TI  - Letters to the editor.

PMID- 19598436
TI  - Methadone in the management of heroin addiction.

PMID- 19598437
TI  - ADSA Vice President Honored-"The Privilege to Recognize".

PMID- 19598438
TI  - Letters to the editor.

PMID- 19598439
TI  - Letters to the editor.

PMID- 19598440
TI  - Letters to the editor.

PMID- 19598442
TI  - Letters to the editor.

PMID- 19598441
TI  - Letters to the editor.

PMID- 19598444
TI  - Anesthesiology externship.

PMID- 19598443
TI  - "This is No Humbug... Gentlemen!!".

PMID- 19598446
TI  - I.v. Sedation - education.

PMID- 19598445
TI  - Inhalation sedation in dental practice.

PMID- 19598447
TI  - Letter to the editor.

PMID- 19598448
TI  - Research foundation and fellowship.

PMID- 19598449
TI  - Letters to the editor.

PMID- 19598450
TI  - Letters to the editor.

PMID- 19598451
TI  - Progress in pain control?

PMID- 19598452
TI  - Abrupt changes take time.

PMID- 19598453
TI  - From the schools.

PMID- 19598454
TI  - The current status of halothane.

PMID- 19598455
TI  - Letters to the editor.

PMID- 19598456
TI  - Letters to the editor.

PMID- 19598457
TI  - Adverse interactions of drugs.

PMID- 19598458
TI  - Postgraduate training in amnesia/analgesia.

PMID- 19598459
TI  - Guidelines for postgraduate courses.

PMID- 19598460
TI  - Letters to the editor.

PMID- 19598461
TI  - Letters to the editor.

PMID- 19598462
TI  - The Time to Act is Now.

PMID- 19598464
TI  - Guidelines for postgraduate and continuing education in pain and anxiety control.

PMID- 19598463
TI  - Where are our guidelines today?

PMID- 19598466
TI  - Questionnaire revisited.

PMID- 19598465
TI  - Letters to the editor.

PMID- 19598468
TI  - "... Gathers no moss".

PMID- 19598467
TI  - Letters to the editor.

PMID- 19598470
TI  - New continuing education course at tufts.

PMID- 19598469
TI  - The discovery of anesthesia.

PMID- 19598471
TI  - Letter to the editor.

PMID- 19598472
TI  - Pulmonary embolus after diazepam sedation.

PMID- 19598473
TI  - The influence of the semisupine position on silent regurgitation.

PMID- 19598475
TI  - Part two: teaching of pain control and management of related complications at the
      advanced education level.

PMID- 19598474
TI  - Nitrous oxide psychosedation in the dental treatment of patients with psychiatric
      disorders: a survey of psychiatrists' opinions.

PMID- 19598477
TI  - Editorial.

PMID- 19598476
TI  - UMKC School of Dentistry Organizes New Department.

PMID- 19598478
TI  - Enflurane ambulatory anesthesia: recovery compared to intravenous anesthesia.

PMID- 19598479
TI  - Intravenous narcotic antagonists in ambulatory oral surgery.
AB  - Results of a study indicate that significant respiratory depression can be
      produced by the intravenous administration of narcotics in the anesthetic
      management of oral surgery patients. Naloxone hydrochloride reversed this
      reaction in all instances. Naloxone is a unique narcotic antagonist in that it
      does not possess agonistic properties of its own, it is effective in reversing
      respiratory depression resulting from all commonly used narcotics and narcotic
      antagonists, it causes no undesirable side effects, and it acts as a placebo when
      administered to a patient who has not had a narcotic. The use of naloxone should
      be considered when a potent narcotic is administered to an ambulatory patient.

PMID- 19598480
TI  - The archaic barbiturate hypnotics.

PMID- 19598482
TI  - Guidelines for the teaching of pain and anxiety control and management of related
      complications in a continuing education program - part three.

PMID- 19598481
TI  - Anesthetic techniques in pennsylvania.

PMID- 19598484
TI  - Self-evaluation.

PMID- 19598485
TI  - Antidepressant drugs.

PMID- 19598483
TI  - New regulations-ohio state dental board.

PMID- 19598486
TI  - Topical anesthesia for periodontal procedures.

PMID- 19598487
TI  - Dental anesthesia training: the harbor general hospital program.

PMID- 19598488
TI  - Recovery from nitrous sedation.

PMID- 19598490
TI  - Successful cardiopulmonary resuscitation following sudden unexpected death-a case
      report.

PMID- 19598489
TI  - The influence of analeptics on central nervous system recovery.

PMID- 19598491
TI  - Letter to the editor.

PMID- 19598492
TI  - The cervical collar-use for posture control in dental anaesthesia.

PMID- 19598493
TI  - Propanolol withdrawal.

PMID- 19598494
TI  - Hepatitis B: risk of infection from antigen-positive medical personnel and
      patients.

PMID- 19598495
TI  - Letters to the editor.

PMID- 19598496
TI  - Letters to the editor.

PMID- 19598497
TI  - Letters to the editor.

PMID- 19598499
TI  - Why monitor?

PMID- 19598498
TI  - Medical-legal update.

PMID- 19598500
TI  - Pharmacology of sedatives for outpatient dentistry.

PMID- 19598501
TI  - S. L. Drummond-jackson memorial fund.

PMID- 19598502
TI  - A new method facilitating nasotracheal intubation.

PMID- 19598503
TI  - A survey of the teaching of pain control at the predoctoral level.

PMID- 19598505
TI  - Letters to the editor.

PMID- 19598504
TI  - Medical-legal update.

PMID- 19598506
TI  - McKesson Issues Alert.

PMID- 19598507
TI  - The 5th conference on pain & anxiety control.

PMID- 19598508
TI  - Letters to the editor.

PMID- 19598510
TI  - Letters to the editor.

PMID- 19598509
TI  - Letters to the editor.

PMID- 19598511
TI  - Chloral hydrate sedation for handicapped children: a double blind study.

PMID- 19598512
TI  - Medical-legal update.

PMID- 19598513
TI  - Letters to the editor.

PMID- 19598514
TI  - Letters to the editor.

PMID- 19598515
TI  - Letters to the editor.

PMID- 19598516
TI  - Dr. William R. Wallace and the ASOS.

PMID- 19598517
TI  - Dr. Daniel f. Lynch - statesman.

PMID- 19598519
TI  - Letters to the editor.

PMID- 19598520
TI  - Letters to the editor.

PMID- 19598518
TI  - Letters to the editor.

PMID- 19598521
TI  - Letters to the editor.

PMID- 19598522
TI  - Letters to the editor.

PMID- 19598523
TI  - Letters to the editor.

PMID- 19598524
TI  - Medical-legal update.

PMID- 19598525
TI  - Cheerfully, SAAD.

PMID- 19598526
TI  - Medical-legal update.

PMID- 19598527
TI  - Letters to the editor.

PMID- 19598528
TI  - Letters to the editor.

PMID- 19598530
TI  - Letters to the editor.

PMID- 19598529
TI  - Letters to the editor.

PMID- 19598531
TI  - Medical-legal update.

PMID- 19598533
TI  - A time to sew and a time to grow.

PMID- 19598532
TI  - Letter to the editor.

PMID- 19598534
TI  - Medical-legal update.

PMID- 19598535
TI  - Letter to the editor.

PMID- 19598537
TI  - Specific cardiac indications for routine lidocaine use.

PMID- 19598536
TI  - The pursuit of excellence.

PMID- 19598539
TI  - Letters to the editor.

PMID- 19598538
TI  - Dentist loses license in child death case.

PMID- 19598540
TI  - Letters to the editor.

PMID- 19598541
TI  - Letters to the editor.

PMID- 19598542
TI  - Medical-legal update.

PMID- 19598543
TI  - Part III - Guidelines for the Teaching of Pain and Anxiety Control and Management
      of Related Complications In a Continuing Education Program.

PMID- 19598544
TI  - International dateline.

PMID- 19598545
TI  - Medical-legal update.

PMID- 19598546
TI  - Letters to the editor.

PMID- 19598547
TI  - Letters to the editor.

PMID- 19598548
TI  - Hypoxemia from sublingual nitroglycerin.

PMID- 19598550
TI  - International dateline.

PMID- 19598549
TI  - Medical-legal update.

PMID- 19598552
TI  - Letters to the editor.

PMID- 19598551
TI  - Letters to the editor.

PMID- 19598553
TI  - Unreasonable insurance premiums.

PMID- 19598554
TI  - Alcohol-drug interactions.

PMID- 19598555
TI  - International dateline.

PMID- 19598556
TI  - Solving the Epinephrine Problem through Plain Arithmetic.

PMID- 19598557
TI  - Medical-legal update.

PMID- 19598558
TI  - Adverse effects of cimetidine.

PMID- 19598559
TI  - Consultation request.

PMID- 19598561
TI  - "Guidelines and the road ahead".

PMID- 19598560
TI  - Letter to the editor.

PMID- 19598562
TI  - International dateline - london.

PMID- 19598564
TI  - Letter to the editor.

PMID- 19598563
TI  - Medical-legal update.

PMID- 19598566
TI  - Dentist anesthesiologist rescues cardiac victim.

PMID- 19598565
TI  - Medical-legal update.

PMID- 19598567
TI  - Anesthesia regulations for dentists for california.

PMID- 19598568
TI  - International dateline.

PMID- 19598569
TI  - Editorial: "Not better nor worse, just different.

PMID- 19598570
TI  - Consultation request.

PMID- 19598571
TI  - Consultant's Response.

PMID- 19598572
TI  - Medical-legal update.

PMID- 19598573
TI  - Letter to the editor.

PMID- 19598574
TI  - Letter to the editor.

PMID- 19598575
TI  - Medical-legal update.

PMID- 19598576
TI  - Shedding some light on the halothane controversy.

PMID- 19598577
TI  - The role of behavioral scientists in the teaching of pain and anxiety control.

PMID- 19598578
TI  - New Concepts in CPR.

PMID- 19598579
TI  - Monitoring Microvascular Reactivity: (II) - Short-Term Effect of Nitrous-Oxide on
      the Peripheral Microcirculation in Humans.
AB  - A study was carried out to monitor directly the short-term effects of N(2)O/O(2)
      inhalation-sedation on the peripheral microcirculation in healthy human subjects
      in a simulated dental setting. The inhalation of 40% N(2)O and 60% O(2) led to a
      small but significant mean percent decrease (-6.89 +/- 1.2 SEM) in relative
      vessel diameter in the nailfold capillaries, for the entire N(2)O-breathing
      period. Individual vessels showed a marked constriction (-31.7% +/- 4.4 SEM, mean
      maximal decrease); the time to this maximum constriction varied with the
      individual vessels. This constriction could not be attributed to changes in
      oxygen or carbon dioxide levels in the alveolar gas, or to changes in heart rate,
      systolic blood pressure, respiratory rate or temperature. Further studies are
      indicated to determine whether this effect is sustained with long term
      administration, and whether it is clinically significant, especially in those
      patients with acquired cardiac disease or those taking vasoactive drugs.

PMID- 19598580
TI  - Medical-legal update.

PMID- 19598581
TI  - Letters to the editor.

PMID- 19598582
TI  - Letters to the editor.

PMID- 19598584
TI  - Letters to the editor.

PMID- 19598583
TI  - Letters to the editor.

PMID- 19598585
TI  - When "mind drugs" also affect the heart.
AB  - Tranquilizers, whether antianxiety or antipsychotic agents, and antidepressants
      have effects on the cardiovascular system that are often overlooked by
      physicians. These effects can range from beneficial mildly antiarrhythmic actions
      to ECG changes that mimic those seen in MI, to heart block, ventricular
      fibrillation, and even death. Knowing which drugs are likely to produce which
      effects is the key to safe prescribing of these widely used and beneficial
      agents.Tranquilizers, including both antianxiety and antipsychotic agents, and
      antidepressants are among the most frequently prescribed drugs in the United
      States today. Yet it is not widely enough appreciated that many of these agents
      have significant cardiovascular effects, some favorable and some adverse. This
      article will serve as a brief review of our knowledge concerning these
      psychotropic agents' effects on the cardiovascular system.

PMID- 19598586
TI  - Teaching intravenous sedation in a general practice residency.

PMID- 19598587
TI  - Conscious sedation: an advanced program in nitrous oxide and an introduction to
      I.v. Techniques for the general practice resident.

PMID- 19598588
TI  - Midazolam: second generation benzodiazepine.

PMID- 19598589
TI  - Letters to the editor.

PMID- 19598590
TI  - Letters to the editor.

PMID- 19598591
TI  - Nitrous oxide hazard.

PMID- 19598592
TI  - Medical-legal update.

PMID- 19598593
TI  - Editorial.

PMID- 19598595
TI  - International dateline.

PMID- 19598594
TI  - Complications of Intravenous Diazepam - Adverse Psychological Reactions. (An
      assessment of 16,000 cases).

PMID- 19598596
TI  - Medical-legal update.

PMID- 19598597
TI  - Letters to the editor.

PMID- 19598598
TI  - Letters to the editor.

PMID- 19598600
TI  - Review of Selected AHA Papers.

PMID- 19598599
TI  - Letters to the editor.

PMID- 19598602
TI  - CPR for Dental Care Providers.

PMID- 19598601
TI  - What's in a Name?

PMID- 19598603
TI  - Medical-legal update.

PMID- 19598605
TI  - Letters to the editor.

PMID- 19598604
TI  - Letters to the editor.

PMID- 19598606
TI  - Letters to the editor.

PMID- 19598607
TI  - Letters to the editor.

PMID- 19598608
TI  - Letters to the editor.

PMID- 19598609
TI  - Letters to the editor.

PMID- 19598610
TI  - Letters to the editor.

PMID- 19598612
TI  - The trigeminal nuclei and selective analgesic drugs.

PMID- 19598614
TI  - Letters to the editor.

PMID- 19598613
TI  - The mechanism of placebo analgesia in postoperative dental pain.

PMID- 19598615
TI  - Letter to the editor.

PMID- 19598616
TI  - "The more things change...".

PMID- 19598617
TI  - Commentary.

PMID- 19598618
TI  - Medical-legal update.

PMID- 19598619
TI  - Letters to the editor.

PMID- 19598620
TI  - Letters to the editor.

PMID- 19598622
TI  - "Itami no kanri".

PMID- 19598621
TI  - Dentist, Officer, CPR Combine to Save Man's Life.

PMID- 19598623
TI  - Washington state adopts new standards for dental administration of anesthesia.

PMID- 19598624
TI  - Letters to the editor.

PMID- 19598625
TI  - Conduction Block Analgesia in the Mandible: A comparative investigation of the
      techniques of Fischer and Gow-Gates.
AB  - An investigation has been made in order to compare two different intraoral
      methods for mandibular block analgesia. The first method (according to Fischer)
      anesthetizes the inferior alveolar and lingual nerves just above the level of the
      mandibular foramen and the other method (according to Gow-Gates) anesthetizes the
      mandibular nerve just after leaving the ovale foramen. The latter method should,
      with only one injection, give complete analgesia within the entire distribution
      zone of the sensory components of the mandibular nerve.The investigation has been
      performed on 12 test subjects, who each have achieved mandibular block analgesia
      according to the two methods mentioned above. 1.8 ml lidocaine-adrenaline (20 mg
      per ml + 12.5 mug per ml) has been used and the analgesic effect has been tested
      in the pulps and in the vestibular and lingual mucosa at different time
      intervals. The investigation shows that the onset of analgesia and complete
      analgesia was more rapid with the first method than with Gow-Gates
      method.Furthermore Gow-Gates' method shows no superiority in anesthetizing the
      long buccal nerve without separate injection for this nerve.However, regarding
      the analgesic effect only, there has been no statistically significant difference
      between the two methods with this small number of test subjects.

PMID- 19598626
TI  - October 1982 preview.

PMID- 19598627
TI  - Medical-legal update.

PMID- 19598628
TI  - Midazolam premedication and lack of recall.

PMID- 19598630
TI  - "Patient Selection is the Key".

PMID- 19598629
TI  - California's New Anesthesia Law.

PMID- 19598632
TI  - Informed consent - the need for standard office procedures.

PMID- 19598631
TI  - Medical-legal update.

PMID- 19598633
TI  - Letter to the editor.

PMID- 19598634
TI  - Medical-legal update.

PMID- 19598635
TI  - From london times - "why dentists go on practising after deaths of patients".

PMID- 19598636
TI  - Editorial.

PMID- 19598637
TI  - Medical-legal update.

PMID- 19598638
TI  - Dear mr. Goulding.

PMID- 19598639
TI  - The changing fellowship exam.

PMID- 19598640
TI  - "Your passport, please".

PMID- 19598641
TI  - Medical-legal update - "potpourri".

PMID- 19598642
TI  - Letters to the editor.

PMID- 19598643
TI  - Letters to the editor.

PMID- 19598644
TI  - Letters to the editor.

PMID- 19598645
TI  - Letters to the editor.

PMID- 19598647
TI  - Naproxen reactions in aspirin sensitive patients.

PMID- 19598646
TI  - Letters to the editor.

PMID- 19598649
TI  - Letter to the editor.

PMID- 19598648
TI  - A case of sick sinus syndrome.

PMID- 19598650
TI  - Medical-legal update.

PMID- 19598651
TI  - Recession in anesthesia training?

PMID- 19598652
TI  - A fresh infusion.

PMID- 19598654
TI  - Medical-legal update.

PMID- 19598653
TI  - ...Dr. Allison responds-.

PMID- 19598655
TI  - Letters to the editor.

PMID- 19598657
TI  - Report of the California Board of Dental Examiners: State of California vs. Tony
      Protopoppas.

PMID- 19598656
TI  - Technical bulletin for malignant hyperthermia.

PMID- 19598658
TI  - Jorgensen memorial lecture: drug interactions.

PMID- 19598659
TI  - The role of the dental anesthesiologist within a major teaching hospital.

PMID- 19598661
TI  - Palatal ulceration: a complication of regional anesthesia of the oral cavity - a
      case report.

PMID- 19598660
TI  - Anaphylaxis following the intravenous administration of methylprednisolone - a
      case report.

PMID- 19598662
TI  - Medical-legal update.

PMID- 19598663
TI  - Response to 20/20 program.

PMID- 19598664
TI  - Anesthesiology residency training for dentists.

PMID- 19598666
TI  - Syncope versus loss of consciousness.

PMID- 19598665
TI  - Establishment of a specialty of dental anesthesiology.

PMID- 19598667
TI  - Response to protopoppas case.

PMID- 19598668
TI  - Response to "20/20" program.

PMID- 19598669
TI  - Response to "20/20" program.

PMID- 19598671
TI  - Use of f.a.d.s.a. Credential.

PMID- 19598672
TI  - Response to "20/20" program.

PMID- 19598670
TI  - Sedation versus General Anesthesia.

PMID- 19598673
TI  - Response to "20/20" program.

PMID- 19598674
TI  - The guidelines for teaching the comprehensive control of pain and anxiety in
      dentistry and the problems confronting the dental profession.

PMID- 19598675
TI  - Professional Liability Insurance for IV Sedation.

PMID- 19598677
TI  - Standards for outpatient anesthesia.

PMID- 19598676
TI  - General Anesthesia versus IV Sedation.

PMID- 19598678
TI  - Standards for outpatient anesthesia.

PMID- 19598679
TI  - Standards for outpatient anesthesia.

PMID- 19598680
TI  - Narcotic sedation for children.

PMID- 19598682
TI  - Narcotic sedation for children.

PMID- 19598681
TI  - Narcotic sedation for children.

PMID- 19598683
TI  - The specialty of anesthesiology in dentistry.

PMID- 19598684
TI  - The introduction of nitrous oxide to clinical practice.

PMID- 19598685
TI  - Inexpensive Outpatient ECG Monitoring.

PMID- 19598686
TI  - Intravenous use of vistaril.

PMID- 19598687
TI  - Revised guidelines for teaching the comprehensive control of pain and anxiety in
      dentistry.

PMID- 19598688
TI  - Dental anesthesiology - the policies of the american dental association in the
      past and its plans for the future.

PMID- 19598690
TI  - EKG Monitoring for Conscious-Sedation.

PMID- 19598689
TI  - Intravenous vistaril.

PMID- 19598691
TI  - Heart block following syncope.

PMID- 19598693
TI  - The need for drug information education in dentistry.

PMID- 19598692
TI  - Proposed Revision, Guidelines for Teaching the Comprehensive Control of Pain and
      Anxiety in Dentistry, Part II.

PMID- 19598694
TI  - Verbal descriptor measures of pain clarify mechanisms of analgesia due to
      narcotics, brain stimulation, and placebo.

PMID- 19598695
TI  - Mechanisms of pain and analgesia.
AB  - An opportunity to develop a new generation of methods for pain relief has arisen
      from recent advances in the neurobiology of pain. A variety of sensitive and
      reliable pain assessment methods are now available to facilitate clinical trials.
      Assessment tools that are suitable for young children are being developed, making
      analgesic research feasible in this group of patients.New analgesic methods may
      either block the action of neurochemical mediators of pain or promote endogenous
      pain-relieving systems. Treatments aimed at preventing peripheral nerve
      sensitization by inflammatory products avoid the side effects of centrally acting
      narcotic analgesics. Endogenous opioid systems are involved in the body's
      analgesic response to acute pain and stress. Pituitary beta-endorphin release is
      a likely component of this response and may be manipulated by pharmacological
      interventions. Noradrenergic and serotonergic pain-inhibiting systems may mediate
      the specific analgesia produced by amitriptyline in neuropathic pain states.

PMID- 19598696
TI  - Assessment and treatment of pain in children with cancer.

PMID- 19598697
TI  - Peripheral pain mechanisms: suppression of postsurgical dental pain with
      antiinflammatory analgesics.

PMID- 19598698
TI  - Neuroendocrine modulation of pain.

PMID- 19598700
TI  - Sensibility threshold in depressive and nondepressive patients with chronic
      orofacial pain.
AB  - Sensibility threshold was measured in patients with depressive and nondepressive
      psychiatric disorders, where both groups were suffering from chronic orofacial
      pain. The control patients had no pain and no signs of mental disturbance.
      Patients with major depressive disorders had a significantly lower sensibility
      threshold than patients with milder depressive disorders, while patients with
      milder depressive disorders had a significantly lower sensibility threshold than
      patients with nondepressive mental disorders. The controls had the highest
      sensibility threshold. Plasma, beta-endorphin, cortisol and prolactin levels were
      also measured. The depressed patients were found to have a lower serum beta
      endorphin level than the nondepressive patients and the controls, although the
      difference was not statistically significant.

PMID- 19598701
TI  - Ohmeda pulse oximeters.

PMID- 19598699
TI  - Endogenous monoamine analgesic systems: amitriptyline in painful diabetic
      neuropathy.

PMID- 19598702
TI  - History of the international Federation of dental anesthesiology societies.

PMID- 19598703
TI  - New approaches to differential diagnosis of chronic orofacial pain.

PMID- 19598704
TI  - Anatomical basis for opening the airway.

PMID- 19598705
TI  - Introduction: evolution in pain and anxiety control.

PMID- 19598706
TI  - A bit of history.

PMID- 19598707
TI  - Editorial.

PMID- 19598708
TI  - The changing relationship of oral and maxillofacial surgery to anesthesia.

PMID- 19598709
TI  - Editorial.

PMID- 19598710
TI  - Editorial.

PMID- 19598711
TI  - Editorial.

PMID- 19598712
TI  - The training of operator-anesthetists.

PMID- 19598713
TI  - Regulation of pediatric oral conscious sedation.

PMID- 19598714
TI  - The lifeblood of this journal.

PMID- 19598715
TI  - Influence of Minor Dental Surgery with and without Intravenous Sedation on Levels
      of Hormones Responsible for Volume Homeostasis in Elderly Hypertensive Patients.
AB  - Changes in the hormones responsible for volume homeostasis were observed before,
      during, and after minor dental surgery in 25 elderly hypertensive patients. These
      patients were divided into two groups. Group L patients were operated on using
      local anesthesia alone. Group LS patients were operated on using local anesthesia
      and intravenous sedation together. We found that plasma renin activity and
      aldosterone and vasopressin levels did not change intraoperatively in either
      group. We also found that intraoperative plasma human atrial natriuretic peptide
      (HANP) levels and systolic blood pressure were significantly elevated in group L
      and significantly decreased in group LS. Before local anesthesia was
      administered, HANP levels in both groups were already higher than the normal
      range in healthy adults. Therefore, these results suggest that increased HANP
      levels represent a compensatory response to offset further elevation of blood
      pressure. However, these increases did not seem to be sufficient to actually
      cause a decrease in blood pressure.

PMID- 19598716
TI  - A clinical evaluation of the analgesic efficacy of preoperative administration of
      ketorolac and dexamethasone following surgical removal of third molars.
AB  - The purpose of this study was to compare the postoperative analgesic efficacy of
      the presurgical intravenous administration of a steroid (dexamethasone), a
      nonsteroidal anti-inflammatory drug (ketorolac), and a combination of the two
      medications. These drugs were administrated preoperatively, and their analgesic
      effects were assessed following the removal of four third molars using
      intravenous sedation (Fentany/Midazolam) and local anesthetic (2% lidocaine with
      1:100,000 epinephrine). Thirty-four patients were randomly assigned to one of
      four groups: Group I (control), saline; Group II, 30 mg ketorolac; Group III, 8
      mg dexamethasone; and Group IV, 30 mg ketorolac + 8 mg dexamethasone. Pain was
      assessed with the Heft-Parker graphic pain rating scale; the initial survey was
      completed preoperatively. The teeth were surgically removed by one of four oral
      and maxillofacial surgeons. Following surgery and initial recovery, the patients
      completed the second survey and were then admitted for overnight observation. The
      patients completed the remaining pain rating scales at 2-hr intervals for 12 hr.
      The last survey was completed at discharge (24 hr postoperatively). A
      postoperative narcotic analgesic was provided upon request (Tylenol 3). Pain data
      were assessed using one-way analysis of variance and the Duncan multiple range
      test (alpha = 0.05). At all postoperative intervals, the greatest pain scores
      were recorded in the control group. Statistically significant differences in pain
      scores were found at the 4-, 6-, 8-, and 10-hr postoperative intervals. At the 2
      hr postoperative interval, pain had increased in all groups, but no differences
      were found among the groups. At the 4- and 6-hr interval, pain levels in Group I
      were significantly greater than those in Group II and Group IV, with Group III
      and IV not significantly different from Group II. At 10 hr, pain levels in the
      saline group were significantly greater than those in all the other groups. At
      all intervals, the only significant differences detected were found between the
      control group and the experimental groups; no significant differences were found
      at any point among any of the experimental groups. The relationship between the
      number of doses of narcotic medication taken postoperatively, and the
      preoperative intravenous regimen was assessed with a Kruskal-Wallis test. No
      significant difference was found among groups with respect to the need for
      postoperative pain medication (P > 0.05). Postoperative analgesia following third
      molar surgery was enhanced in the first 10 hr with the preoperative
      administration of ketorolac. The addition of dexamethasone did not improve the
      analgesic effect.

PMID- 19598718
TI  - How good are your anesthesia records?

PMID- 19598717
TI  - Patient-controlled sedation.
AB  - Patient-controlled sedation was utilized in patients aged 15 to 85 yr who were
      undergoing surgery under local or regional anesthesia. Midazolam, propofol, and
      methohexitone were used, either by themselves or in combination with fentanyl or
      alfentanil. Sedation was mild to moderate in the majority of patients, and
      operating conditions were good. The sedation method provided patients the ability
      to control the sedation and to vary the degree of sedation according to the
      environment and to the stress of the procedure. Sedation of the elderly, which
      tends to be problematic, was made easy using this method, and the elderly
      patients appeared to enjoy the option. The problems encountered were
      oversedation, respiratory depression, pain during injection, and postural
      hypotension.

PMID- 19598719
TI  - Plasma levels of 2% lidocaine with 1:100,000 epinephrine with young children
      undergoing dental procedures.
AB  - Lidocaine levels were determined for 12 children, aged 55 to 150 mo, who received
      routine dental treatment, including multiple intraoral injections of 2% lidocaine
      (2.6 to 6.4 mg/kg) with 1:100,000 epinephrine. Peak plasma concentrations of
      lidocaine ranged from 0.7 to 3.8 mug/ml at 5 to 15 min postinjection. Generally
      accepted threshold concentrations for the onset of central nervous system
      toxicity are 5 to 10 mug/ml. In this study, no child approached these levels when
      given local anesthesia for dental procedures.

PMID- 19598720
TI  - A survey of local anesthesia course directors.
AB  - This study was designed to present local anesthesia course directors with
      detailed information that can be used in assessing and improving their courses. A
      questionnaire was mailed to the directors of local anesthesia courses in all
      dental schools in the United States and Puerto Rico. The results indicate that
      oral surgery/oral and maxillofacial surgery departments are involved in 89% of
      predoctoral local anesthesia courses and that a typical course has 15 hr of
      didactic and 5 hr of clinical instruction, with a 1:4 faculty:student ratio
      during the portion of clinical instruction that involves administering injections
      to classmates. Although an average course content can be derived from the data,
      the survey revealed quite a bit of diversity in terms of programs of instruction.
      The program designs, injections covered, instructional materials used, and
      protocols followed in the event of ineffective anesthetization all warrant
      consideration by those interested in the way in which instruction in local
      anesthesia occurs.

PMID- 19598721
TI  - Flunitrazepam versus placebo premedication for anxiety control in general dental
      practice.
AB  - Our objective was to examine the performance of sublingual administration of the
      short- to intermediate-acting benzodiazepine flunitrazepam on patients with
      dental anxiety. The study was designed as a randomized double-blind, placebo
      controlled crossover trial with nearly identical dental interventions performed
      on two separate occasions in 24 adult patients. Flunitrazepam (1 mg)
      significantly reduced anxiety and was well tolerated. With few exceptions, both
      the patients and the dentist clearly favored the session with flunitrazepam. Most
      patients also preferred the remaining part of the day when they had been
      premedicated with flunitrazepam. They were apparently not particularly troubled
      by being somewhat drowsy. Dizziness was not reported as a problem. Flunitrazepam
      appears to be an effective, safe, and recommendable alternative for premedication
      of anxious dental patients.

PMID- 19598723
TI  - 9th international dental congress on modern pain control: a new millennium in
      analgesia, sedation and anesthesia jerusalem, Israel, may 2-5, 2000.

PMID- 19598722
TI  - Treatment of local anesthetic toxicity.

PMID- 19598724
TI  - Who will be administering dental office anesthesia in the 21st century?

PMID- 19598726
TI  - Charles K. Teter, D.D.S.

PMID- 19598725
TI  - A Re-evaluation of Guedel's Stages of Anesthesia: With particular reference to
      the ambulatory dental general anesthetic patient.

PMID- 19598727
TI  - Do You Know?: Fires and Explosions.

PMID- 19598728
TI  - The Dentist and the Hospital Operating Room, An Editorial.

PMID- 19598729
TI  - A Patient's Misinterpretation of a Commonly-Used Word (A Case Report).

PMID- 19598731
TI  - Letters to the Editor.

PMID- 19598730
TI  - The Importance of Teaching Dentists the Technic of Intravenous Injection.

PMID- 19598733
TI  - In the Beginning.

PMID- 19598732
TI  - Letters to the Editor.

PMID- 19598734
TI  - The Dentist-Anesthesiologist in Civil Defense.

PMID- 19598735
TI  - The Management of Anesthetic Problems in Dentistry.

PMID- 19598736
TI  - General Anesthesia - Training and Teaching.

PMID- 19598737
TI  - The Stress Phenomenon in Anesthesiology.

PMID- 19598738
TI  - Needed in Dentistry - More Post Postgraduate Courses.

PMID- 19598739
TI  - Cooperation between Medicine and Dentistry.

PMID- 19598740
TI  - Survey of Anesthetic Fatalities in Oral Surgery and a Review of the Etiological
      Factors in Anesthetic Deaths.

PMID- 19598741
TI  - Premedication for the Ambulatory General Anesthetic Patient.

PMID- 19598742
TI  - Premedication Prior to General Anesthesia.

PMID- 19598744
TI  - Premedication.

PMID- 19598743
TI  - The Psychology of Premedication.

PMID- 19598746
TI  - A Plea for Disposable Anesthetic Carpules with Attached Sterile Needles.

PMID- 19598745
TI  - "Overspecialization" in Dentistry.

PMID- 19598747
TI  - Reducing the Fear of General Anesthesia.

PMID- 19598748
TI  - Premedication of Children for Ambulatory General Anesthesia.

PMID- 19598749
TI  - Anesthesia Limited Practice in Dentistry: The Gross and Net in Office Anesthesia.

PMID- 19598750
TI  - Neraval, Evipal, Pentothal, Surital: A Clinical Evaluation.

PMID- 19598751
TI  - Do You Know?: Fires and Explosions.

PMID- 19598752
TI  - Short Courses in Hypnosis.

PMID- 19598753
TI  - "Fellowship" in the International Association of Anesthesiologists.

PMID- 19598754
TI  - The Physiology and Pharmacology of Mandibular Block Anesthesia.

PMID- 19598756
TI  - Cooperation Between the Obstetrician and the Dentist.

PMID- 19598755
TI  - The Use of Promethazine for Premedication.

PMID- 19598757
TI  - Letters to the Editor.

PMID- 19598758
TI  - Dental Anesthesia for the Cerebral Palsied.

PMID- 19598759
TI  - Cardiac Arrest, Tracheotomy, Aspiration-Why All the Fuss?

PMID- 19598760
TI  - Thinking Positively.

PMID- 19598761
TI  - Outline of Course in Anesthesiology at the University of Pittsburgh.

PMID- 19598762
TI  - Duocaine-A New Local Anesthetic Agent - A Clinical Research Report.

PMID- 19598763
TI  - Nisentil and Lorfan in Dentistry.

PMID- 19598764
TI  - Patient Refractive to Lidocaine Anesthesia - Case Report.

PMID- 19598765
TI  - Our Responsibility to Anesthesiology in Dentistry.

PMID- 19598766
TI  - A.D.S.A. House of Delegates.

PMID- 19598767
TI  - Who Discovered General Anesthesia?

PMID- 19598769
TI  - Use of Hypnosis in Dentistry: (A Condensation).

PMID- 19598768
TI  - Relaxation Through Hypnosis, a Valuable Adjunct to Chemo-Anesthesia.

PMID- 19598770
TI  - Insurance Notes: Professional Liability Insurance.

PMID- 19598772
TI  - Disposable Needles Again Urged for Dental Local Anesthesia.

PMID- 19598771
TI  - Clinical and Laboratory Studies in Plasma Cholinesterases.

PMID- 19598773
TI  - Letters to the Editor.

PMID- 19598774
TI  - Letters to the Editor.

PMID- 19598776
TI  - Our Greater Responsibility.

PMID- 19598775
TI  - Insurance Notes.

PMID- 19598777
TI  - Civil Defense Training for Dentists.

PMID- 19598778
TI  - Comparative Study of Pentothal, Surital and Neraval in Ambulatory Anesthesia.

PMID- 19598779
TI  - Research in Anesthesiology.

PMID- 19598780
TI  - Medicine and the Law: National Interprofessional Code for Physicians and
      Attorneys.

PMID- 19598781
TI  - Fluothane for Ambulatory Dental Procedures: A Brief Research Report.

PMID- 19598782
TI  - The Use of the Cardiac Monitor in Anesthesia for Dental Procedures - A Brief
      Research Report.

PMID- 19598783
TI  - A.D.A. Centennial Year Begins.

PMID- 19598784
TI  - Anesthesia Abstracts Section Starts.

PMID- 19598785
TI  - Why Does the Anesthesiologist Sit on a Stool?

PMID- 19598787
TI  - Semantics in Anesthesiology in Dentistry.

PMID- 19598786
TI  - Prevention of Medical Emergencies in Patients with Pre-Existing Medical Disease.

PMID- 19598788
TI  - "Is Heat Sterilization of Local Anesthetic Drugs a Necessity?".

PMID- 19598789
TI  - Editorial Comments: The Fund for Dental Education - Its Relationship to the
      Future of Dental Education and Dentistry.

PMID- 19598790
TI  - Negligence of Anesthetist Causing Patient to Swallow False Teeth Held Question
      for Jury.

PMID- 19598791
TI  - A Study of Analgesia and Anesthesia with Special Reference to Trichlorethylene.

PMID- 19598792
TI  - Pediatric General Anesthesia in a Private Practice.

PMID- 19598793
TI  - New Horizons in the Field of Hypnosis Education.

PMID- 19598794
TI  - Welcome! Journal of Oral Surgery, Anesthesia and Hospital Dental Service.

PMID- 19598795
TI  - Generalizations About Dentists Who Use General Anesthesia.

PMID- 19598796
TI  - Editorial Comments.

PMID- 19598797
TI  - Letters to the Editor.

PMID- 19598799
TI  - Mendel Nevin, D.D.S.

PMID- 19598798
TI  - Emergency Tracheotomy.

PMID- 19598800
TI  - "Doctor's Day" and the Discovery of Anesthesia.

PMID- 19598801
TI  - The George Washington Bridge and the A.D.S.A. Visit to New York.

PMID- 19598803
TI  - Short Courses in General Anesthesia.

PMID- 19598802
TI  - The Anesthesia of the Future - General and Local Analgesia.

PMID- 19598804
TI  - I Attended a Short Course in Hypnosis.

PMID- 19598805
TI  - Hypnosis is Easy but Psychodynamics Comes First.

PMID- 19598806
TI  - Curriculum Survey of the Teaching of Anesthesiology in American Dental Schools.

PMID- 19598807
TI  - Malpractice as Related to the Anesthesiologist.

PMID- 19598808
TI  - Dentists in Medical Anesthesiology.

PMID- 19598809
TI  - The Relationship of the Fund for Dental Education to the Future of Anesthesiology
      in Dentistry.

PMID- 19598810
TI  - Another Forward Step in Dental Education.

PMID- 19598811
TI  - Refutation of Letter on Hypnosis.

PMID- 19598812
TI  - Proposed Changes in the Society's Constitution and By-Laws.

PMID- 19598813
TI  - Report of the Council on Legislation of the American Dental Association on the
      Use of Anesthetics by Dentists.

PMID- 19598814
TI  - American Dental Association.

PMID- 19598815
TI  - The Florida Society of Anesthesiologists.

PMID- 19598816
TI  - Letters to the Editor.

PMID- 19598818
TI  - Letters to the Editor.

PMID- 19598817
TI  - The Florida Society of Anesthesiologists.

PMID- 19598820
TI  - Balanced Anesthesia.

PMID- 19598819
TI  - Experimentation in Man.

PMID- 19598821
TI  - Is American Dentistry a Specialty of Medicine?

PMID- 19598823
TI  - A.S.A. Undertakes Building Program.

PMID- 19598822
TI  - What Are We Talking About?

PMID- 19598824
TI  - Recruitment for Dentistry.

PMID- 19598825
TI  - Thiopental Sodium in Ambulatory Anesthesia.

PMID- 19598826
TI  - Ambulatory Endotracheal Anesthesia with Trichlorethylene Supplement for Operative
      Dentistry.

PMID- 19598828
TI  - Rebuttal to Editorial "Dentists in Medical Anesthesiology".

PMID- 19598827
TI  - Succinylcholine Chloride as a Supplemental Agent in Ambulatory Dental Anesthesia.

PMID- 19598829
TI  - Hospital Dentistry and the General Practitioner.

PMID- 19598830
TI  - Kurt H. Thoma, M.D.

PMID- 19598831
TI  - An Urgent Need in Radiological Research.

PMID- 19598832
TI  - Disagreement with Editorial "Dentists in Medical Anesthesiology".

PMID- 19598833
TI  - Highlights of the Sixth Annual Convention.

PMID- 19598834
TI  - Pittsburgh, Pennylvania Mecca of Anesthesiology in Dentistry.

PMID- 19598835
TI  - The Relationship of the Postanesthetic Period to an Appraisal of Modern
      Ambulatory Anesthesia Technics.

PMID- 19598836
TI  - The Start of an Adventure in Japan.

PMID- 19598838
TI  - A Cursory Glance at Japanese Dentistry and Anesthesiology.

PMID- 19598837
TI  - Cardiac Resuscitation Course.

PMID- 19598839
TI  - Teaching of Anesthesia, and Its Relation to Dental Education.

PMID- 19598840
TI  - An Aid to Stabilization of the Anesthesia Inhaler.

PMID- 19598841
TI  - Letter from Japan.

PMID- 19598842
TI  - Newer Drugs in General Anesthesia.

PMID- 19598843
TI  - The History of General Anesthesia: Published in the Hartford (Conn.) Courant,
      Dec. 9, 1846.

PMID- 19598844
TI  - The Anesthesia Literature and Dental Anesthesia.

PMID- 19598845
TI  - Editorial Comments.

PMID- 19598846
TI  - Sidelines of a Mission.

PMID- 19598847
TI  - How Dentist Anesthesiologists can Assist Physician Anesthesiologists.

PMID- 19598848
TI  - The Confusion and Unscientific Attitude in the "Hypnosis Movement".

PMID- 19598849
TI  - Editorial Comment.

PMID- 19598851
TI  - Dental Anaesthetic Progress in Britain.

PMID- 19598850
TI  - Visiting Japanese Dentistry.

PMID- 19598852
TI  - The American Society of Oral Surgeons and the A.D.S.A.

PMID- 19598853
TI  - The Need for Regulation of Specialty Training Programs.

PMID- 19598854
TI  - Editorial Comment: From the News Bulletin of the New Jersey Dental Society of
      Anesthesiology.

PMID- 19598856
TI  - A Visit to a Japanese Leprosarium.

PMID- 19598855
TI  - Report on Anesthesia Activities in England.

PMID- 19598857
TI  - Hypoxia: Its Causes and Symptoms.

PMID- 19598859
TI  - A New Philosophy of Artificial Resuscitation.

PMID- 19598858
TI  - History of General Anesthesia (Part II).

PMID- 19598861
TI  - The Department of Oral Surgery and Anesthesia of the College of Dentistry of Ohio
      State University.

PMID- 19598860
TI  - The Brain Wave Synchronizer.

PMID- 19598863
TI  - Resuscitation Equipment for Use in Dental Offices.

PMID- 19598862
TI  - Congratulations to Ohio Chemical.

PMID- 19598864
TI  - Two Maga-Tamas for a General Anesthetic.

PMID- 19598865
TI  - Sidelights on Japan's No. 1 City.

PMID- 19598866
TI  - Resuscitation in the Dental Office.

PMID- 19598868
TI  - A Dental Intern's Reaction to the Hospital.

PMID- 19598867
TI  - History of General Anesthesia - Part III: Address by Gardner Q. Colton at the
      Wells Memorial Celebration in Hartford, 1894.

PMID- 19598870
TI  - To All Dental Interns.

PMID- 19598869
TI  - The Importance of Recent Changes in the Pennsylvania State Dental Practice Act to
      Anesthesiology in Dentistry.

PMID- 19598871
TI  - The Far-Reaching Implications of the Changes in the Pennsylvania Dental Practice
      Act, Particularly in Regard to Conducting a Physical Evaluation.

PMID- 19598872
TI  - Hospital Dentistry and General Anesthesia.

PMID- 19598873
TI  - Responses to Hypnosis Editorial from March J.A.D.S.A: The Confusion and
      Unscientific Attitude in the "Hypnosis Movement".

PMID- 19598874
TI  - Responses to Hypnosis Editorial from March J.A.D.S.A: The Confusion and
      Unscientific Attitude in the "Hypnosis Movement".

PMID- 19598875
TI  - Responses to Hypnosis Editorial from March J.A.D.S.A: The Confusion and
      Unscientific Attitude in the "Hypnosis Movement".

PMID- 19598876
TI  - Responses to Hypnosis Editorial from March J.A.D.S.A: The Confusion and
      Unscientific Attitude in the "Hypnosis Movement".

PMID- 19598878
TI  - Profile of a Japanese "Park Avenue Dentist".

PMID- 19598877
TI  - The Dilemma of Postgraduate Anesthesiology Education and Clinical Application.

PMID- 19598879
TI  - Ambulatory Patient Screening for General Anesthesia.

PMID- 19598881
TI  - JADSA to Offer Free Reprints to Contributors.

PMID- 19598880
TI  - Commonly Used Hospital Abbreviations.

PMID- 19598882
TI  - Component Representation in Los Angeles.

PMID- 19598883
TI  - California Plays Host to the A.D.S.A.

PMID- 19598884
TI  - Component Anonymity.

PMID- 19598885
TI  - Oral Surgeons Can Attend Two Conventions.

PMID- 19598886
TI  - New Journal of Clinical Pharmacology and Therapeutics Appears.

PMID- 19598887
TI  - Welcome to the City of Angels.

PMID- 19598888
TI  - Letter to the Editor.

PMID- 19598889
TI  - A Brief Research Report on the Use of "Amnalgesia" for Oral Surgery.

PMID- 19598890
TI  - The Importance of an Open Vein During General Anesthesia.

PMID- 19598891
TI  - House of Delegates Meeting in Los Angeles.

PMID- 19598892
TI  - "Anesthesia is Awfully Simple or Simply Awful".

PMID- 19598893
TI  - Editorial Comment.

PMID- 19598895
TI  - Itinerant Anesthesia - A New Problem in Dental Anesthesiology.

PMID- 19598894
TI  - Itinerant Anesthesia - A New Problem in Dental Anesthesiology.

PMID- 19598896
TI  - Editorial: Board of Directors Resolution on Limitation of the Use of
      Anesthesiology by Dentists.

PMID- 19598898
TI  - Hypnosis in Dentistry.

PMID- 19598897
TI  - A Preliminary Study on Carbocaine.

PMID- 19598899
TI  - Audio-Analgesia May Be Hazardous.

PMID- 19598901
TI  - When Is a General Anesthesia Patient Ready to be Dismissed?

PMID- 19598900
TI  - Precaution in Premedication.

PMID- 19598902
TI  - Dental Abstracts - A Journal Every Dentist Should Read.

PMID- 19598903
TI  - Pro-Anesthetic Instructions.

PMID- 19598905
TI  - Premature Advertising Claims Made for Audio-Analgesia.

PMID- 19598904
TI  - Editorial Comment: Closed-Chest Cardiac Massage.

PMID- 19598906
TI  - Dentistry in Hospitals.

PMID- 19598907
TI  - Sterilization of Dental Equipment with Particular Reference to Local Anesthetic
      Materials.

PMID- 19598909
TI  - In the Future of Anesthesiology.

PMID- 19598908
TI  - New Information on the Mechanism of Peripheral Nerve Block with Local
      Anesthetics.

PMID- 19598910
TI  - A Projection of Trends in Dental Education.

PMID- 19598911
TI  - Letters to the Editor.

PMID- 19598912
TI  - Anesthesia with Fluothane.

PMID- 19598914
TI  - Problems of Contamination and the Advantages of the Disposable Dental Needle.

PMID- 19598913
TI  - A Brief Clinical Report of the Use of Brevital, 1/2 Per Cent, for General
      Anesthesia in Oral Surgery.

PMID- 19598915
TI  - Anesthesia for Handicapped Children.

PMID- 19598917
TI  - Letters to the Editor.

PMID- 19598916
TI  - The Sad Story of Johnny Commonsense.

PMID- 19598918
TI  - Fluothane for Out-Patient Dentistry.

PMID- 19598919
TI  - "Elephant Gun" Anesthesia.

PMID- 19598920
TI  - The F.D.I.-1961.

PMID- 19598921
TI  - Anesthesia in Dentistry.

PMID- 19598922
TI  - Use of Hostacain-Spezial, A New Local Anesthetic Agent, in Oral Surgery: (A
      preliminary brief research report).

PMID- 19598924
TI  - A Controversial Editorial - Seven Years Later.

PMID- 19598923
TI  - Anyone for a Symposium?

PMID- 19598926
TI  - Methohexital Anaesthesia.

PMID- 19598925
TI  - Publishing Scientific Talks.

PMID- 19598928
TI  - "Dental Anesthesia" - A Potentially Harmful Term.

PMID- 19598927
TI  - Pain.

PMID- 19598929
TI  - The Ideal Anesthetic Agent.

PMID- 19598930
TI  - Final Observations of Japanese Dentistry.

PMID- 19598931
TI  - Letter to the Editor.

PMID- 19598933
TI  - A Fond Farewell.

PMID- 19598932
TI  - An Intra-Nasal Insufflator - A Supplementary Device for Dental Out-Patient
      Anesthesia.

PMID- 19598934
TI  - International Conference on Oral Surgery.

PMID- 19598935
TI  - Anesthesia is Ever Changing.

PMID- 19598936
TI  - Ambulatory Anesthesia for Dental Patients.

PMID- 19598938
TI  - Editorial.

PMID- 19598937
TI  - Current Court Cases with Comment.

PMID- 19598939
TI  - Another Dimension.

PMID- 19598940
TI  - Dr. Bruno H. Harms, of Omaha, Nebraska, Recipient of the Eighth Annual Heidbrink
      Award.

PMID- 19598941
TI  - Considerations in Determining Preoperative Medication for Children.

PMID- 19598944
TI  - Dues.

PMID- 19598943
TI  - Guest Editorial.

PMID- 19598945
TI  - Anesthesia of the 5th Nerve and its Branches by the Extra-Oral Approach.

PMID- 19598946
TI  - The Use of Sodium Brevital in 1/2 Per Cent Solution.

PMID- 19598947
TI  - The Dentist and Civil Defense.

PMID- 19598948
TI  - How Big Are We?

PMID- 19598949
TI  - Management of Certain Poor Risk Dental Patients.

PMID- 19598951
TI  - Editorial - Dental Anaesthesia.

PMID- 19598950
TI  - Public Relation in Dentistry.

PMID- 19598952
TI  - Letters to the Editor.

PMID- 19598954
TI  - Safe Anesthesia.

PMID- 19598953
TI  - Management of Medical-Dental Problems in Patients with Cardiovascular Diseases.

PMID- 19598956
TI  - Restoration of Life via Closed-Chest Cardiac Resuscitation.

PMID- 19598955
TI  - Considerations in Resuscitation.

PMID- 19598957
TI  - Cardiovascular Responses to Local Dental Anesthesia with Epinephrine in
      Normotensive and Hypertensive Subjects.

PMID- 19598958
TI  - Editorial.

PMID- 19598960
TI  - Letters to the Editor.

PMID- 19598959
TI  - Letters to the Editor.

PMID- 19598961
TI  - An Evaluation of 2-Chloroprocaine HCl as a Local Anesthetic Agent in the Dental
      Office.

PMID- 19598962
TI  - Purpose of a Dental Journal.

PMID- 19598963
TI  - Answer to Mr. Arnold Newman, Cardiac Division Manager, The Birtcher Corporation.

PMID- 19598964
TI  - Answer to Mr. Arnold Newman, Cardiac Division Manager, The Birtcher Corporation.

PMID- 19598965
TI  - Restorative Dentistry Under General Anesthesia Utilizing a Non-Intubation
      Technique.

PMID- 19598966
TI  - The Teaching of Specialties in Dental Schools.

PMID- 19598967
TI  - Letters to the Editor.

PMID- 19598968
TI  - Justice Reversed?

PMID- 19598970
TI  - Where are the Members?

PMID- 19598969
TI  - Case Reports: Case of Death by Subcutaneous Injection of Oxygen.

PMID- 19598972
TI  - A.D.S.A. Announces Workshop.

PMID- 19598971
TI  - The Universal Anesthesia Stand.

PMID- 19598973
TI  - Anesthesia in the Hospital versus the Dental Office.

PMID- 19598974
TI  - Letters to the Editor.

PMID- 19598975
TI  - Premedication and Local Anesthesia in Pediatric Dentistry.

PMID- 19598976
TI  - Case Reports.

PMID- 19598977
TI  - Cardiac Resuscitation.

PMID- 19598978
TI  - The Future of Local Anesthesia.

PMID- 19598979
TI  - A Hand for the Handicapped.

PMID- 19598980
TI  - Teaching Workshop a Reality.

PMID- 19598982
TI  - Case Report Section.

PMID- 19598981
TI  - Letters to the Editor.

PMID- 19598983
TI  - The Need to Improve Scientific Writing.

PMID- 19598984
TI  - Comparative Results of Methohexital Sodium and Thiopental Sodium Used During Out
      Patient General Anesthesia (A Double-Blind Study).

PMID- 19598985
TI  - Study on the General Anesthesia of Dental Out-patients in Japan: with Particular
      Reference to Fluothane Nitrous Oxide and Oxygen Anesthesia.

PMID- 19598987
TI  - Avoiding Malpractice Suits.

PMID- 19598986
TI  - Administration of an Anesthetic.

PMID- 19598988
TI  - A New Survey on the Teaching of Anesthesiology in Dental Education.

PMID- 19598989
TI  - Case Reports.

PMID- 19598990
TI  - The American Dental Society of Anesthesiology.

PMID- 19598991
TI  - A Dream Come True.

PMID- 19598992
TI  - Operative Dentistry Under General Anesthesia for the Non-Handicapped.

PMID- 19598993
TI  - Case Reports.

PMID- 19598994
TI  - Utilization of Research by the Practitioner.

PMID- 19598995
TI  - Pyrrocaine HCl - A Preliminary Clinical Study of Its Uses in Oral Surgery.

PMID- 19598996
TI  - Death by Anesthesia.

PMID- 19598997
TI  - Case Reports.

PMID- 19598999
TI  - Bruce L. Douglas, President of the A.D.S.A.

PMID- 19598998
TI  - Report of the President to the House of Delegates.

PMID- 19599000
TI  - Case Reports.

PMID- 19599001
TI  - Letter to the Editor.

PMID- 19599002
TI  - The A.D.S.A. After a Decade.

PMID- 19599004
TI  - The Halothane Controversy.

PMID- 19599003
TI  - The American Dental Society of Anesthesiology.

PMID- 19599006
TI  - The New Look.

PMID- 19599005
TI  - Guest Editorial.

PMID- 19599007
TI  - Halothane: Special Survey of Current Reports.

PMID- 19599008
TI  - Basic Physiology of Local Anesthesia.

PMID- 19599009
TI  - Case Reports.

PMID- 19599010
TI  - Guest Editorial: The American Dental Society of Anesthesiology.

PMID- 19599012
TI  - November 22-24 Dallas, Texas.

PMID- 19599011
TI  - Letters to the Editor.

PMID- 19599013
TI  - Letters to the Editor.

PMID- 19599015
TI  - Case Report No. 8.

PMID- 19599014
TI  - The Use of Dexamethasone-21-Phosphate for the Reduction of Laryngeal Edema in
      Intubation Anesthesia.

PMID- 19599016
TI  - Medical and Dental Instrumentation in the Treatment of Viral Hepatitis.

PMID- 19599017
TI  - Society for the Advancement of Anaesthesia in Dentistry.

PMID- 19599018
TI  - Letter to the Editor.

PMID- 19599020
TI  - Editorial: Student Contributions to A.D.S.A.

PMID- 19599019
TI  - The Evolution of Pain Control in Dentistry.

PMID- 19599021
TI  - Workshop Proceedings to be Published.

PMID- 19599022
TI  - Letters to the Editor.

PMID- 19599023
TI  - Progress Notes in Anesthesiology in Dentistry.

PMID- 19599024
TI  - The Use of Mouth Protectors in General Anesthesia.

PMID- 19599025
TI  - Postoperative Hepatic Necrosis.

PMID- 19599026
TI  - Pre-Registration Required for Annual Meeting.

PMID- 19599027
TI  - Synergestic Anesthesia.

PMID- 19599028
TI  - Case Report.

PMID- 19599029
TI  - The Case for Atropine in the Prevention of Cardiac Arrest.

PMID- 19599030
TI  - Case Report.

PMID- 19599031
TI  - Use of Vasoconstrictors in Local Anesthetic Solutions for Patients with
      Cardiovascular Disease.

PMID- 19599032
TI  - "I Have Returned".

PMID- 19599033
TI  - A Trip to Pennsylvania.

PMID- 19599034
TI  - Where To Train in Anesthesiology?

PMID- 19599035
TI  - Anesthesiology in the Hospital.

PMID- 19599036
TI  - Case Reports.

PMID- 19599037
TI  - Editorials.

PMID- 19599038
TI  - San Francisco - 1964.

PMID- 19599039
TI  - A.D.A. Section on Anesthesiology.

PMID- 19599041
TI  - Journal of Oral Surgery Resumes Original Name.

PMID- 19599040
TI  - Society To Meet with Chicago Midwinter Meeting.

PMID- 19599042
TI  - Legislative Bills on Dentist's Right To Give I.V. Injection.

PMID- 19599043
TI  - A Quarter Century Anniversary for Anesthesiology.

PMID- 19599044
TI  - General Anesthesia Coverage in Dental Prepayment Plans.

PMID- 19599046
TI  - Letters to the Editor.

PMID- 19599045
TI  - Notes on the Management of Emergencies.

PMID- 19599048
TI  - The Dentist and the Hospital.

PMID- 19599047
TI  - Dentistry in Accredited Hospitals.

PMID- 19599049
TI  - Briefing Component Societies.

PMID- 19599050
TI  - Just Plain Arithmetic.

PMID- 19599051
TI  - Pain That is Real.

PMID- 19599053
TI  - Sample Consent Forms.

PMID- 19599052
TI  - Special Issue on the Law.

PMID- 19599054
TI  - Dr. Timmons Urges Dentists To "Step Up and Be Counted".

PMID- 19599055
TI  - Second Conference on Teaching of Pain Control.

PMID- 19599056
TI  - Solving the Epinephrine Problem.

PMID- 19599058
TI  - The President's Page.

PMID- 19599057
TI  - Hospital Dentistry.

PMID- 19599059
TI  - Dentistry Under General Anesthesia.

PMID- 19599060
TI  - Dr. Norman Trieger, A Profile.

PMID- 19599061
TI  - The Case of the Itinerant Anesthesiologist.

PMID- 19599062
TI  - Who Belongs?

PMID- 19599063
TI  - Profile-Donald B. Giddon.

PMID- 19599065
TI  - Editorial.

PMID- 19599064
TI  - Extrapyramidal Syndrome from Prolixin.

PMID- 19599066
TI  - Wanted: Oral Surgeons.

PMID- 19599067
TI  - Observations Regarding The Recovery Phase Of Intravenous Methohexital Sodium
      Anesthesia.

PMID- 19599068
TI  - Derangements Of Cerebral Physiology By Anesthetic Agents Or Techniques.

PMID- 19599070
TI  - Extrapyramidal Syndrome Due to Phenothiazines.

PMID- 19599069
TI  - Meperidine Idiosyncrasy.

PMID- 19599071
TI  - Anesthesiologists - World Federation.

PMID- 19599073
TI  - Patient Management.

PMID- 19599072
TI  - Is Nitrous Oxide Teratogenic?

PMID- 19599074
TI  - Editorial.

PMID- 19599075
TI  - Derangements of Cerebral Physiology by Anesthetic Agents or Techniques.

PMID- 19599076
TI  - Presidential Perceptions.

PMID- 19599077
TI  - Drug Abuse Law Effective Feb. 1.

PMID- 19599078
TI  - Contact Lenses - A Hazard Under General Anesthesia In the Dental Office.

PMID- 19599079
TI  - A Planned Public Relations.

PMID- 19599080
TI  - Volume 3 Issue 10, November, 1956.

PMID- 19599081
TI  - Volume 3 Issue 11, December, 1956.

PMID- 19599082
TI  - Anesthesia for the General Practitioner.

PMID- 19599083
TI  - Ethyl Chloride Anesthesia.

PMID- 19599084
TI  - Notes and Quotes from the Literature.

PMID- 19599085
TI  - Trends of General Anesthesia in Dentistry.

PMID- 19599086
TI  - Mechanical Aids in Dental Anesthesiology.

PMID- 19599087
TI  - Anesthetic Terminology.

PMID- 19599090
TI  - Mechanical Aids in Dental Anesthesiology.

PMID- 19599088
TI  - The Discovery of General Anesthesia.

PMID- 19599092
TI  - Letters to the Editor.

PMID- 19599093
TI  - Letters to the Editor.

PMID- 19599089
TI  - Research-The Basis of Scientific Progress.

PMID- 19599094
TI  - Anesthesia for the Patient with Cardiovascular Disease for Ambulatory Oral
      Surgery.

PMID- 19599091
TI  - The Clinical Significance of Anesthetic Terminology.

PMID- 19599095
TI  - Mechanical Aids in Dental Anesthesiology: Conversion of Patient Controlled
      Analgesic Apparatus to a Combination of Patient and Operator Control.

PMID- 19599096
TI  - The Use of Epinephrine in Local Anesthetic Solutions for the Patient with Cardiac
      and Circulatory Disturbances.

PMID- 19599097
TI  - Anesthetic Terminology: Spasm.

PMID- 19599098
TI  - Hearing Aid Monitors Breathing of Unconscious Patients.

PMID- 19599100
TI  - Notes and Quotes from the Literature.

PMID- 19599101
TI  - Memoirs.

PMID- 19599099
TI  - Dentistry Has Reached Maturity.

PMID- 19599102
TI  - Memoirs (Continued from March Issue).

PMID- 19599104
TI  - The Challenge of the Hospital to Dental Education.

PMID- 19599103
TI  - The Training of Dentists in the Field of General Anesthesia.

PMID- 19599106
TI  - Memoirs, (continued from April issue).

PMID- 19599105
TI  - Safety in the Use of Small Quantities of Local Anesthetics.

PMID- 19599107
TI  - Letters to the Editor.

PMID- 19599109
TI  - Fire and Explosion Hazards in Anesthetizing Locations.

PMID- 19599108
TI  - Section on Anesthesiology of the Council on Scientific Session.

PMID- 19599111
TI  - A.D.S.A. Membership.

PMID- 19599110
TI  - Letters to the Editor.

PMID- 19599113
TI  - Are You Interested in the Definition of Oral Surgery?

PMID- 19599112
TI  - Specialization and Anesthesiology in Dentistry.

PMID- 19599114
TI  - The Experts' Column.

PMID- 19599115
TI  - Random Thoughts on Anesthesiology from the Rural Dental Practice.

PMID- 19599116
TI  - Letters to the Editor.

PMID- 19599118
TI  - The Importance of the Basic Sciences.

PMID- 19599117
TI  - Cooperation Between Medicine and Dentistry.

PMID- 19599119
TI  - Aspirating Technics in Local Anesthesia for Dental Procedures.

PMID- 19599120
TI  - Notes and Quotes from the Literature.

PMID- 19599121
TI  - Regional Anesthesiology.

PMID- 19599122
TI  - An Historical Sketch on Local Anesthesia.

PMID- 19599123
TI  - The Value of Having a Vasoconstrictor in Local Anesthetic Solutions.

PMID- 19599124
TI  - The Importance of the Basic Sciences in Local Anesthesia.

PMID- 19599125
TI  - Would You Do It to Yourself?

PMID- 19599126
TI  - Do You Know?: Fires and Explosions.

PMID- 19599127
TI  - Post Thiopental Tremors.

PMID- 19599128
TI  - A Declaration of Interdependence.

PMID- 19599129
TI  - The American Dental Society of Anesthesiology: The Past, the Present and the
      Future.

PMID- 19599130
TI  - Sterilization in Local Anesthesia.

PMID- 19599131
TI  - Milk Supplies.

PMID- 19599132
TI  - Plumbing Reform.

PMID- 19599133
TI  - Pseudo-filtration.

PMID- 19599135
TI  - The Effect of Noise upon Weak and Nervous People.

PMID- 19599134
TI  - Death Rate Fallacies.

PMID- 19599136
TI  - "Some Considerations Concerning City Noises.".

PMID- 19599137
TI  - Preventive Therapeutics.

PMID- 19599138
TI  - Veterinary Sanitation.

PMID- 19599139
TI  - Municipal Sanitation.

PMID- 19599140
TI  - Vital Statistics.

PMID- 19599141
TI  - Canadian Notes.

PMID- 19599142
TI  - Sanitary Engineering.

PMID- 19599143
TI  - Laboratory Work.

PMID- 19599144
TI  - Dirt and Disease.

PMID- 19599145
TI  - Individual Hygiene.

PMID- 19599146
TI  - Cerebro-Spinal Meningitis.

PMID- 19599147
TI  - Powers of Health Boards.

PMID- 19599148
TI  - Veterinary Sanitation.

PMID- 19599149
TI  - Municipal Sanitation.

PMID- 19599150
TI  - Sanitary Engineering.

PMID- 19599151
TI  - Canadian Notes.

PMID- 19599153
TI  - American Public Health Association.

PMID- 19599152
TI  - Preventive Therapeutics.

PMID- 19599154
TI  - Reporting of Ophthalmia.

PMID- 19599155
TI  - The Brown-Tail Moth.

PMID- 19599156
TI  - Preventive Therapeutics.

PMID- 19599158
TI  - Sanitary Engineering.

PMID- 19599157
TI  - Municipal Sanitation.

PMID- 19599159
TI  - Vital Statistics.

PMID- 19599160
TI  - Laboratory Work.

PMID- 19599161
TI  - The Writing of Health Reports.

PMID- 19599163
TI  - Rabies.

PMID- 19599162
TI  - American Public Health Association.

PMID- 19599164
TI  - Recent Outbreak of Typhoid Fever at Springfield.

PMID- 19599165
TI  - Municipal Sanitation.

PMID- 19599166
TI  - Sanitary Engineering.

PMID- 19599167
TI  - Laboratory Notes.

PMID- 19599168
TI  - Veterinary Hygiene.

PMID- 19599170
TI  - Executive Sanitarians as Specialists.

PMID- 19599169
TI  - Canadian Notes.

PMID- 19599171
TI  - The Relations of Executive to Technical Men.

PMID- 19599172
TI  - Chicago Vital Statistics.

PMID- 19599173
TI  - What is the Relation of Human and Bovine Tuberculosis, and How Does It Affect
      Inmates of Public Institutions?

PMID- 19599174
TI  - Causes of Deaths in Providence, 1856-1905.

PMID- 19599175
TI  - Municipal Sanitation.

PMID- 19599176
TI  - Sanitary Engineering Notes.

PMID- 19599178
TI  - Preventive Therapeutics.

PMID- 19599177
TI  - Laboratory Notes.

PMID- 19599180
TI  - Some Personal Experiences with the Gypsy and Brown-tail Moths.

PMID- 19599179
TI  - Veterinary Sanitation.

PMID- 19599181
TI  - The Work of Suppressing the Gypsy and Brown-tail Months.

PMID- 19599183
TI  - Sanitary Engineering Notes.

PMID- 19599182
TI  - Municipal Sanitation.

PMID- 19599184
TI  - Laboratory Notes.

PMID- 19599185
TI  - Preventive Therapeutics.

PMID- 19599186
TI  - Chicago Vital Statistics Again.

PMID- 19599187
TI  - The Real Significance of Bacterial Standards (Counts) for Milk.

PMID- 19599188
TI  - Some of the Advantages of Certified Milk.

PMID- 19599189
TI  - The Projected Work of the Milk Commissioners of the Suffolk District Medical
      Society.

PMID- 19599191
TI  - Municipal Sanitation.

PMID- 19599190
TI  - National Pure Food Law and Its Possible and Probable Effect upon the Food Supply
      of Massachusetts.

PMID- 19599192
TI  - Veterinary Sanitation.

PMID- 19599194
TI  - The Method of Release of Diphtheria patients in Providence.

PMID- 19599193
TI  - The Value of Two Consecutive Negative Cultures as a Method of Releasing
      Diphtheria Patients.

PMID- 19599196
TI  - New Managing Editor.

PMID- 19599195
TI  - Statement concerning Journal.

PMID- 19599197
TI  - Municipal Sanitation.

PMID- 19599198
TI  - Sanitary Engineering Notes.

PMID- 19599199
TI  - Laboratory Notes.

PMID- 19599200
TI  - The Sanitary Conference.

PMID- 19599201
TI  - Terminal Disinfection-Reasons and Methods.

PMID- 19599202
TI  - Municipal Sanitation.

PMID- 19599203
TI  - Sanitary Engineering Notes.

PMID- 19599204
TI  - Laboratory Notes.

PMID- 19599205
TI  - Books and Pamphlets Reviewed.

PMID- 19599206
TI  - Tropical Medicine, with Special Reference to the West Indies, Central America,
      Hawaii and the Philippines.

PMID- 19599207
TI  - The Advance of Sanitation in Mexico.

PMID- 19599209
TI  - Leprosy in Massachusetts-Its Diagnosis and Segregation.

PMID- 19599208
TI  - The Mexico City Meeting of the American Public Health Association.

PMID- 19599210
TI  - Rabies in Massachusetts-Symptoms, Importance of early Diagnosis and Practical
      Methods for its Suppression.

PMID- 19599212
TI  - Reorganization of the Health Dept. of Indianapolis.

PMID- 19599211
TI  - Milk Commissions of the United States-A Synopsis of their Work.

PMID- 19599213
TI  - Present Status of Morphological Types of B. diphtheriae.

PMID- 19599214
TI  - Pasteurization of Milk.

PMID- 19599215
TI  - Pasteurization of Milk for Public Sale.

PMID- 19599216
TI  - Finger Prints and Vital Statistics.

PMID- 19599217
TI  - Chemical Laboratory Notes.

PMID- 19599218
TI  - Personal Hygiene.

PMID- 19599219
TI  - Veterinary Hygiene.

PMID- 19599220
TI  - Preventive Therapeutics.

PMID- 19599222
TI  - Sanitary Engineering Notes.

PMID- 19599221
TI  - Municipal Sanitation.

PMID- 19599223
TI  - The Trained Nurse as a Special Domestic Sanitary Supervisor.

PMID- 19599225
TI  - Diphtheria, Sewer Gas and Infection.

PMID- 19599224
TI  - The American Public Health Association.

PMID- 19599226
TI  - Recent Public Health Legislation.

PMID- 19599227
TI  - Recent Public Health Legislation.

PMID- 19599228
TI  - Communications.

PMID- 19599229
TI  - Chemical Laboratory Notes.

PMID- 19599230
TI  - Personal Hygiene.

PMID- 19599232
TI  - Municipal Sanitation.

PMID- 19599231
TI  - Veterinary Hygiene.

PMID- 19599233
TI  - Sanitary Engineering Notes.

PMID- 19599234
TI  - Time Limit versus Culture Limit in Diphtheria Release.

PMID- 19599235
TI  - Chairman's Address, The Laboratory Section of the American Public Health
      Association.

PMID- 19599236
TI  - The Possibilities of a Clinical Laboratory in a Country Town in Relation to
      Public Health Work.

PMID- 19599237
TI  - Observations on the Present-Day Milk Situation.

PMID- 19599238
TI  - Biological Laboratory Notes.

PMID- 19599239
TI  - Chemical Laboratory Notes.

PMID- 19599240
TI  - Personal Hygiene.

PMID- 19599241
TI  - Municipal Sanitation.

PMID- 19599243
TI  - The Diagnosis of Rabies.

PMID- 19599242
TI  - Sanitary Engineering Notes.

PMID- 19599244
TI  - Communications.

PMID- 19599245
TI  - The Determination of Intestinal Bacteria in Milk.

PMID- 19599246
TI  - The Relative Value of Dextrose Broth, Phenol Broth and Lactose-Bile as Enrichment
      Media for the Isolation of B. Coli.

PMID- 19599247
TI  - Time Limit versus Culture Limit in Diphtheria Release.

PMID- 19599248
TI  - Preservatives in Food and the Effect thereof on the Public Health.

PMID- 19599249
TI  - The Ophthalmo-Tuberculin Test.

PMID- 19599250
TI  - A Few Remarks on the Prevalence of Venereal Disease.

PMID- 19599251
TI  - Impression Preparations and the Van Gieson Stain for Negri Bodies.

PMID- 19599252
TI  - What Should Be the Attitude of Boards of Health toward Venereal Diseases.

PMID- 19599254
TI  - Chemical Laboratory Notes.

PMID- 19599253
TI  - Biological Laboratory Notes.

PMID- 19599255
TI  - Personal Hygiene.

PMID- 19599256
TI  - Veterinary Hygiene.

PMID- 19599257
TI  - Municipal Sanitation.

PMID- 19599259
TI  - Canadian Notes.

PMID- 19599258
TI  - Sanitary Engineering Notes.

PMID- 19599260
TI  - Preservation of Foods by Cold.

PMID- 19599261
TI  - Federal Supervision of Biologic Therapeutic Products.

PMID- 19599262
TI  - Some Factors in the Spread of Typhoid Fever.

PMID- 19599263
TI  - Notes on the Use of Smith's Solution and Bile Media.

PMID- 19599265
TI  - Normal Waters of Illinois.

PMID- 19599264
TI  - A Method of Calculating the Numbers of B. Coli from the Results of Dilution
      Tests.

PMID- 19599267
TI  - The Specific Nature of Anaphylaxis.

PMID- 19599266
TI  - The Antiseptic and Germicidal Properties of Solutions of Formaldehyde and their
      Action upon Toxins.

PMID- 19599268
TI  - Note on Method of Determining Total and Volatile Suspended Matter in Sewage.

PMID- 19599269
TI  - The Transmission and Methods for Control of Measles.

PMID- 19599270
TI  - The Function of Health Boards in the Control of Tuberculosis.

PMID- 19599271
TI  - Personal Hygiene.

PMID- 19599272
TI  - Municipal Sanitation.

PMID- 19599273
TI  - Sanitary Engineering Notes.

PMID- 19599275
TI  - Preventive Therapeutics.

PMID- 19599274
TI  - Vital Statistics.

PMID- 19599277
TI  - Communications.

PMID- 19599276
TI  - Miscellaneous Notes.

PMID- 19599279
TI  - How can Psychiatry assist Preventive Medicine?

PMID- 19599278
TI  - A Federal Department of Health.

PMID- 19599280
TI  - School Hygiene.

PMID- 19599281
TI  - The Determination of Oxygen Consumed in Waters.

PMID- 19599282
TI  - Effect of Heating upon the Determination of Leucocytes in Milk.

PMID- 19599283
TI  - Diphtheria Diagnosis.

PMID- 19599284
TI  - The Mathematics of the Bacterial Count.

PMID- 19599285
TI  - The House-Fly as an Agent in the Dissemination of Infectious Diseases.

PMID- 19599287
TI  - Sex Hygiene for Young Men, Circular No. 1.

PMID- 19599286
TI  - The Disinfection of Books.

PMID- 19599288
TI  - Sex Hygiene for Young Men, Circular No. 2.

PMID- 19599289
TI  - Chemical Laboratory Notes.

PMID- 19599290
TI  - Personal Hygiene.

PMID- 19599292
TI  - Municipal Sanitation.

PMID- 19599291
TI  - Veterinary Hygiene.

PMID- 19599293
TI  - Sanitary Engineering Notes.

PMID- 19599294
TI  - Vital Statistics.

PMID- 19599295
TI  - It is Time to Act.

PMID- 19599296
TI  - Personal versus Public Hygiene.

PMID- 19599297
TI  - President's Address.

PMID- 19599298
TI  - Improvement of the Municipal Sanitary Inspection Service.

PMID- 19599299
TI  - The Rural Health Officer.

PMID- 19599300
TI  - Communications.

PMID- 19599302
TI  - Veterinary Hygiene.

PMID- 19599301
TI  - Personal Hygiene.

PMID- 19599303
TI  - Municipal Sanitation.

PMID- 19599304
TI  - Sanitary Engineering Notes.

PMID- 19599305
TI  - Vital Statistics.

PMID- 19599306
TI  - A Personal Word.

PMID- 19599307
TI  - Disposal of Municipal Refuse.

PMID- 19599308
TI  - Address of the Chairman.

PMID- 19599309
TI  - The Mortality from Industrial Diseases.

PMID- 19599310
TI  - The Need of Greater Uniformity and Accuracy in Statistical Expression.

PMID- 19599311
TI  - Notification and Morbility Returns in Cuba with Special Reference to Yellow Fever
      and Other Major Infectious Diseases.

PMID- 19599313
TI  - The Survival of B. Typhosus in Milk when Used in Ordinary Breakfast-Table Coffee
      and Tea.

PMID- 19599312
TI  - Protection of Public Milk Supplies from Specimens Contaminated with Pus
      Organisms.

PMID- 19599314
TI  - The Work of the State Inspectors of Health and its Relation to the Work of Local
      Boards of Health.

PMID- 19599315
TI  - The American Health League.

PMID- 19599316
TI  - The Practice of Exposikg Food Stuffs to the Street Dust and its Effect upon the
      Public Health.

PMID- 19599317
TI  - The Revival of Field Inspection.

PMID- 19599318
TI  - Personal Hygiene.

PMID- 19599319
TI  - Veterinary Hygiene.

PMID- 19599321
TI  - Sanitary Engineering Notes.

PMID- 19599320
TI  - Municipal Sanitation.

PMID- 19599322
TI  - Biological Laboratory Notes.

PMID- 19599323
TI  - A Simple Procedure for the Disinfection of Passenger Coaches, and to Kill Vermin
      in Them.

PMID- 19599324
TI  - Measures to Promote the Health of School Children.

PMID- 19599326
TI  - Some Aspects of the Alcohol Question.

PMID- 19599325
TI  - Measures to Promote the Health of School Children.

PMID- 19599327
TI  - Health Problems of Provinces.

PMID- 19599329
TI  - Sociology of the Middle and Far West.

PMID- 19599328
TI  - Health Problems in Alberta.

PMID- 19599331
TI  - The Rat as a Factor in Disease.

PMID- 19599330
TI  - Social and Public Health Development of the Northwestern States and of the
      Western Central Provinces of Canada.

PMID- 19599332
TI  - Yellow Fever in Mexico.

PMID- 19599333
TI  - The Relation of State or Provincial Boards to Municipal Boards and Local Health
      Officers.

PMID- 19599334
TI  - Study of Diphtheria Observed in Guadalajara, Mexico, from the 1st of January,
      1904, Until June 30, 1908, from a Hygienic Standpoint.

PMID- 19599335
TI  - Tuberculosis and Poverty.

PMID- 19599336
TI  - Some Remarks upon the Result of the Preventive Treatment of Rabies and its
      Present State.

PMID- 19599337
TI  - The Best Method of Vaccinating with Humanized Lymph.

PMID- 19599338
TI  - The Determination of the Typhoid Bacillus in Infected Water and Milk.

PMID- 19599339
TI  - A Method of Determining the Number of Dust Particles in Air.

PMID- 19599340
TI  - Abstract of Report of the Committee on Standard Methods for the Bacterial
      Diagnosis of Typhoid Fever.

PMID- 19599341
TI  - Abstract of Report of the Committee on Standard Methods for the Diagnosis of
      Rabies.

PMID- 19599342
TI  - Abstract of the Report of the Committee on Standard Methods for the
      Bacteriological Diagnosis of Tuberculosis.

PMID- 19599343
TI  - Committee on Standard Methods for the Bacterial Diagnosis of Glanders.

PMID- 19599344
TI  - Public Health, A New Profession.

PMID- 19599346
TI  - Harmony in Public Health Work.

PMID- 19599345
TI  - Training for Public Health Service.

PMID- 19599347
TI  - Notes on the Voges and Proskauer Reaction.

PMID- 19599348
TI  - Typhoid Fever in the Province of Manitoba with Special Regard to the City of
      Winnipeg.

PMID- 19599349
TI  - Characteristics of Typhoid Fever in the Middle West.

PMID- 19599351
TI  - Typhoid Bacilli Carriers.

PMID- 19599350
TI  - The Differentiation of Outbreaks of Typhoid Fever Due to Water, Milk, Flies and
      Contact.

PMID- 19599352
TI  - Investigation of Typhoid Fever Epidemic at Sheboygan, Wisconsin.

PMID- 19599353
TI  - Morbidity and Mortality Statistics of Typhoid Fever in the Middle West.

PMID- 19599354
TI  - The Epidemiological Diagnosis and Treatment of Typhoid Outbreaks.

PMID- 19599355
TI  - Certain Conclusions Concerning Typhoid Fever in the South, as Deduced from a
      Study of Typhoid Fever in Richmond, Va.

PMID- 19599357
TI  - Dextrose vs Lactose for Determining Colon Bacilli.

PMID- 19599356
TI  - Methods of Determining Nitrates in Sewages and Waters of High Chlorine Content.

PMID- 19599359
TI  - Co-ordination of Laboratory Work and Inspection in Supervising Milk Supplies.

PMID- 19599358
TI  - A Method for Staining Negri Bodies.

PMID- 19599360
TI  - Experiments on Putrescibility Tests for Sewage and Sewage Effluent.

PMID- 19599362
TI  - Plural Deaths as Index of Fatality.

PMID- 19599361
TI  - The Result of Reincubation and Reinoculation of Diphtheria Cultures.

PMID- 19599363
TI  - Limitations of the Application of Crude Death Rates.

PMID- 19599364
TI  - Mortality Statistics in Canada.

PMID- 19599365
TI  - Problems of Quarantine in Contagious Disease Work.

PMID- 19599366
TI  - Management of Infectious Diseases in Rural Municipalities.

PMID- 19599367
TI  - Disinfection of Rooms.

PMID- 19599368
TI  - Pleasures and Hopes of the Health Officer.

PMID- 19599370
TI  - Diseased Meat and its Relation to Meat Inspection.

PMID- 19599369
TI  - Cow Faeces as a Source of Tubercle Bacilli in Milk.

PMID- 19599371
TI  - Personal Hygiene.

PMID- 19599372
TI  - Veterinary Hygiene.

PMID- 19599373
TI  - Municipal Sanitation.

PMID- 19599374
TI  - Biological Laboratory Notes.

PMID- 19599375
TI  - Chemical Laboratory Notes.

PMID- 19599376
TI  - Telling the Truth to the Health Officer.

PMID- 19599377
TI  - Relation of Health Officer to Medical Profession.

PMID- 19599378
TI  - Inductive Public Hygiene.

PMID- 19599379
TI  - The Principles of Smokeless Combustion.

PMID- 19599380
TI  - Pollution of the Great Lakes.

PMID- 19599381
TI  - State Control of Public Water Supplies.

PMID- 19599382
TI  - Water Problems of Illinois and Neighboring States.

PMID- 19599383
TI  - Water Problems of the Middle West.

PMID- 19599384
TI  - Diseases of the North West of Canada: Sanitary Precautions and Results.

PMID- 19599385
TI  - The Commercial Pasteurization of Milk.

PMID- 19599386
TI  - Routine Counts of Bacteria in Water Supplies.

PMID- 19599387
TI  - Determination of Nitrates by Reduction with Alum.

PMID- 19599388
TI  - A Study of Certain Paracolon Forms Found in Polluted Deep Wells.

PMID- 19599390
TI  - Aesculin Bile Salt Media for Milk Analysis.

PMID- 19599389
TI  - Aesculin Bile Salt Media for Water Analysis.

PMID- 19599392
TI  - Some Freak Results from Animal Inoculations.

PMID- 19599391
TI  - Relative Proportion of Bacteria in Top and Bottom Milk.

PMID- 19599393
TI  - The Most Economical Ratio of Permanganate to Formaldehyde in Practical
      Disinfection.

PMID- 19599394
TI  - Longevity of B. Tuberculosis in Sputum.

PMID- 19599396
TI  - Typhoid Fever: Incidence of the Disease as Contracted within the Mass. General
      Hospital from 1899 to 1908.

PMID- 19599395
TI  - The Maryland Biometer.

PMID- 19599397
TI  - Protective Inoculation against Typhoid Fever.

PMID- 19599398
TI  - Bacteria in Sewer Air.

PMID- 19599399
TI  - Personal Hygiene.

PMID- 19599400
TI  - Municipal Sanitation.

PMID- 19599401
TI  - Vital Statistics.

PMID- 19599403
TI  - Death of Dr. Quitman N. Kohnke.

PMID- 19599402
TI  - Veterinary Hygiene.

PMID- 19599404
TI  - Public Health and the American Public Health Association.

PMID- 19599405
TI  - Some of the Present Needs of the American Public Health Association.

PMID- 19599406
TI  - Public Laboratories Vs. Private Laboratories.

PMID- 19599408
TI  - Sanitary Supervision of Communicable Diseases by the Department of Public Health.

PMID- 19599407
TI  - The Prevention of Infant Mortality.

PMID- 19599409
TI  - Results of Federal Control of Viruses, &c.

PMID- 19599410
TI  - Scope of Public Health Work Vs. Dependence.

PMID- 19599411
TI  - Care of Phthisis in Out-Door Schools.

PMID- 19599412
TI  - Day Camp Treatment for Tuberculosis.

PMID- 19599413
TI  - Educational Measures for Prevention of Tuberculosis.

PMID- 19599414
TI  - Home Management of Consumptives.

PMID- 19599415
TI  - Personal Hygiene.

PMID- 19599416
TI  - Veterinary Hygiene.

PMID- 19599417
TI  - Municipal Sanitation.

PMID- 19599418
TI  - Sanitary Engineering Notes.

PMID- 19599419
TI  - Chemical Laboratory Notes.

PMID- 19599420
TI  - Biological Laboratory Notes.

PMID- 19599422
TI  - The Importance of Population Vital Statistics and Their Treatment Actuarially.

PMID- 19599421
TI  - The Economist and His Relation to the Problem of Conservation of Human Resources.

PMID- 19599423
TI  - American Birth Registration.

PMID- 19599424
TI  - The Budapest System of Death Classification.

PMID- 19599425
TI  - Trade Mortality Statistics.

PMID- 19599426
TI  - Smallpox in the United States.

PMID- 19599428
TI  - Insanity in Immigrants.

PMID- 19599427
TI  - Report of an Epidemic of Probable Paratyphoid Fever.

PMID- 19599430
TI  - The Importance of Registration and Control of Cases of Laryngeal and Pulmonary
      Tuberculosis.

PMID- 19599429
TI  - An Improved Bubbling Drinking Fountain.

PMID- 19599431
TI  - Ophthalmia Neonatorum-Facts Concerning Its Prevention.

PMID- 19599432
TI  - Personal Hygiene.

PMID- 19599433
TI  - Veterinary Hygiene.

PMID- 19599434
TI  - Municipal Sanitation.

PMID- 19599435
TI  - Sanitary Engineering Notes.

PMID- 19599436
TI  - Biological Laboratory Notes.

PMID- 19599437
TI  - The Prevention of Typhoid Fever in City and Country Districts.

PMID- 19599438
TI  - The Management of Milk Borne Outbreaks of Typhoid Fever.

PMID- 19599439
TI  - The Relation of Typhoid Fever to the Water Supplies of Illinois.

PMID- 19599441
TI  - Utility of the Domiciliary Visit in the Campaign against Yellow Fever.

PMID- 19599440
TI  - The Saloon and the Health Officer.

PMID- 19599442
TI  - The Campaign against Yellow Fever on the Isthmus of Tehuantepec.

PMID- 19599443
TI  - Report on Yellow Fever in the Mexican Republic from the 16th of August, 1909, to
      Date.

PMID- 19599444
TI  - A Limited Outbreak of Typhoid Fever Due to a Double Water Supply.

PMID- 19599445
TI  - Methods of Control of Communicable Disease by Boards of Health, Especially in
      Small Communities.

PMID- 19599446
TI  - The Arrangement and Phrasing of Public Health Regulations.

PMID- 19599447
TI  - The Prevention of the Spread of Contagious Diseases Particularly among Children.

PMID- 19599448
TI  - Preliminary Report on the Tuberculin Test as Applied to a City's Milk Supply.

PMID- 19599449
TI  - The Clean Milk Campaign in Hamilton.

PMID- 19599450
TI  - The Problem of Ventilation.

PMID- 19599451
TI  - Damage Suits for Typhoid Fever.

PMID- 19599452
TI  - Is Housing Reform Worth While?

PMID- 19599453
TI  - County Officers of Health.

PMID- 19599454
TI  - A Method of Sealing Test Tubes to Prevent Evaporation of Culture Media.

PMID- 19599455
TI  - Age Problems in Industrial Hygiene.

PMID- 19599456
TI  - The Protection of Factory Employees against Dust Arising from Certain
      Occupations.

PMID- 19599457
TI  - The Ventilation of Industrial Establishments.

PMID- 19599458
TI  - The Sex Problems in Industrial Hygiene.

PMID- 19599459
TI  - The Relation of Life Insurance to Public Hygiene.

PMID- 19599460
TI  - The Physiological Aspects of Ventilation.

PMID- 19599461
TI  - Incineration of Municipal Wastes with Utilization.

PMID- 19599462
TI  - Disposal of City Wastes and Consideration of Nuisances in Edmonton, Alberta,
      Canada.

PMID- 19599463
TI  - The School Nurse as an Aid to Medical Inspection of Schools.

PMID- 19599464
TI  - The Control of a Large Milk Supply.

PMID- 19599465
TI  - The Relation of Public Water Supplies to General and Specific Mortalities in
      Cities.

PMID- 19599466
TI  - The Need of Quantitative Methods in Epidemiological Work.

PMID- 19599467
TI  - Period of Incubation of Inoculation Rabies.

PMID- 19599468
TI  - Franklin C. Robinson.

PMID- 19599469
TI  - Dry Air and Its Effect on Health.

PMID- 19599470
TI  - Boston and Chicago Death Rates.

PMID- 19599471
TI  - Condensed Milk and Its Value for General Use and for Infant Feeding.

PMID- 19599472
TI  - Personal Hygiene.

PMID- 19599473
TI  - Veterinary Hygiene.

PMID- 19599476
TI  - Reporting Outbreaks of Animal Diseases.

PMID- 19599474
TI  - Sanitary Engineering Notes.

PMID- 19599477
TI  - Saving Time in Work of Local Boards of Health.

PMID- 19599479
TI  - The Teaching of Hygiene and Sanitation in the Schools.

PMID- 19599478
TI  - The Improvement of Public Health through Teaching of Hygiene in the Elementary
      Schools.

PMID- 19599480
TI  - Teaching of Hygiene in Normal Schools.

PMID- 19599481
TI  - Organization of the Public School Hygiene Service in the Federal District of
      Mexico.

PMID- 19599482
TI  - Instructive Inspection.

PMID- 19599484
TI  - Sanitary Education in California by Means of a Traveling Railroad Exhibit.

PMID- 19599483
TI  - The Value and Scope of Exhibitions and Museums.

PMID- 19599485
TI  - Scope and Nature of Publicity as a Factor in Popular Educational Movements in
      Public Health.

PMID- 19599487
TI  - The Necessity of Isolating Prostitutes Who Suffer from Syphilis.

PMID- 19599486
TI  - The Necessity of Some Efficient Means of Checking Syphilitic and Gonorrheal
      Contamination.

PMID- 19599488
TI  - Some Considerations on Vaccinal Syphilis.

PMID- 19599490
TI  - Co-operative Efforts in the Supervision and Control of Milk Supplies.

PMID- 19599489
TI  - The Second Decennial Revision of the International Classification of Causes of
      Death.

PMID- 19599491
TI  - How an Enlarged and More Uniform National Health Administration May be Secured.

PMID- 19599492
TI  - Some Observations Regarding the Maritime Prophylaxis of Pulmonary Tuberculosis.

PMID- 19599493
TI  - Prophylactic Measures in Exanthematic Typhus.

PMID- 19599494
TI  - Relations between the Sanitary and Politico-Administrative Authorities in the
      Mexican Republic.

PMID- 19599495
TI  - Some Facts Indicating That Malaria May be Spread through Other Agencies Than the
      Anopheles Mosquito.

PMID- 19599496
TI  - An Investigation of the Extent of the Bacterial Pollution of the Atmosphere by
      Mouth-Spray.

PMID- 19599497
TI  - The Sanitary Requirements of Ventilation.

PMID- 19599498
TI  - The Sanitary Education of the People.

PMID- 19599499
TI  - Reply on Behalf of the United States.

PMID- 19599500
TI  - Utilization of Bacteriologic and Microscopic Methods in the Inspection of Milk.

PMID- 19599501
TI  - The Organization of the Municipal Health Department at Vera Cruz.

PMID- 19599502
TI  - What May be Done to Improve the Hygiene of the City Dweller.

PMID- 19599503
TI  - Police Health Census of the City of Baltimore, 1906.

PMID- 19599504
TI  - How Shall the Registration of Vital Statistics be Obtained in the South.

PMID- 19599505
TI  - Studies on Inhibition, Attenuation and Rejuvenation of B. Coli.

PMID- 19599506
TI  - Contribution to the Microscopical Investigation of Haematozoon Malariae.

PMID- 19599507
TI  - Bacteriological Methods for Air Analysis.

PMID- 19599508
TI  - Longevity of B. Diphtheriae on Swabs.

PMID- 19599509
TI  - A Standard Fumigating Outfit for a Single Room.

PMID- 19599510
TI  - Importance of Standard Methods for Testing Disinfectants.

PMID- 19599512
TI  - The Control of Algal Pollution in the Reservoirs of the Canal Zone.

PMID- 19599511
TI  - An Analytical and Epidemiological Study of Farm Water Supplies.

PMID- 19599513
TI  - A Comparative Study of Fecal Streptococci from the Horse, the Cow and Man.

PMID- 19599515
TI  - Artificial Milk: A Substitute for Ordinary Milk as a Laboratory Medium.

PMID- 19599514
TI  - The Determination of the Number of Body Cells in Milk by a Direct Method.

PMID- 19599516
TI  - The Bacterial Flora of Milk Held at Low Temperatures.

PMID- 19599517
TI  - The Bacteremia Theory of Tuberculosis: A Refutation.

PMID- 19599519
TI  - Pancreatin-Bile Salt Medium for the Detection of B. Coli in Water.

PMID- 19599518
TI  - Note on an Organism Isolated from Washington Tap Water, Aggluginated Readily by
      the Serum of Typhoid Fever Patients.

PMID- 19599520
TI  - A Biochemical Reaction for Detecting Pollution in Water Supplies.

PMID- 19599522
TI  - Titles of Papers Appearing on Section Programs.

PMID- 19599521
TI  - An Opinion Upon the Outbreak of Typhoid Fever at St. Vincent's Infant Asylum,
      Baltimore County, Md., During July and August, 1909.

PMID- 19599523
TI  - The Importance of Contact Infection.

PMID- 19599524
TI  - Modern Methods of Quarantine.

PMID- 19599525
TI  - Personal Hygiene.

PMID- 19599526
TI  - Veterinary Hygiene.

PMID- 19599527
TI  - Sanitary Engineering Notes.

PMID- 19599530
TI  - The Journal of the American Public Health Association-An Announcement.

PMID- 19599528
TI  - Biological Laboratory Notes.

PMID- 19599531
TI  - Correlation of Public Health Movements. The California Plan.

PMID- 19599532
TI  - The Real Reason for State and Municipal Meat Inspection.

PMID- 19599533
TI  - Some Recent Progress in Sewage Disposal.

PMID- 19599534
TI  - The Hygiene of the Swimming Pool.

PMID- 19599535
TI  - The Spread of Scarlet Fever and Diphtheria in Schools.

PMID- 19599536
TI  - Water Analysis and the Public Health.

PMID- 19599537
TI  - The Functions of a Public Health Laboratory.

PMID- 19599538
TI  - A Comparison of the Germicidal Value of a Few Coal-Tar Disinfectants.

PMID- 19599539
TI  - A New Form of Anaerobic Jar.

PMID- 19599541
TI  - The International Hygiene Exhibition.

PMID- 19599540
TI  - Social Economics and Public Health.

PMID- 19599543
TI  - Infantile Paralysis.

PMID- 19599542
TI  - Cholera.

PMID- 19599544
TI  - Municipal Sanitation.

PMID- 19599545
TI  - Biological Laboratory Notes.

PMID- 19599546
TI  - Sanitary Engineering Notes.

PMID- 19599548
TI  - Veterinary Hygiene.

PMID- 19599547
TI  - Personal Hygiene.

PMID- 19599550
TI  - EDITORIALS: ANNOUNCEMENT OF COMMITTEE ON JOURNAL.

PMID- 19599551
TI  - PRESIDENT'S ADDRESS.

PMID- 19599552
TI  - THE INTER-RELATION OF NATIONAL ORGANIZATIONS WORKING IN THE INTEREST OF HEALTH.

PMID- 19599553
TI  - ON THE PROPER CORRELATION OF PHYSICIANS, ENGINEERS AND OTHER SPECIALISTS, IN
      PUBLIC HEALTH WORK.

PMID- 19599554
TI  - Section of Municipal Health Officers: THE VALUE OF TERMINAL DISINFECTION.

PMID- 19599555
TI  - MODERN METHODS OF CONTROLLING THE SPREAD OF ASIATIC CHOLERA.

PMID- 19599556
TI  - Section on Vital Statistics: THE IMPORTANCE OF BIRTH REGISTRATION TO DETERMINE
      INFANT MORTALITY.

PMID- 19599557
TI  - Laboratory Section: CHAIRMAN'S ADDRESS: THE PAST PERFORMANCES OF THE LABORATORY
      SECTION WITH SOME SUGGESTIONS FOR THE FUTURE.

PMID- 19599558
TI  - THE EFFECT OF VACUUM DESSICATION UPON THE VIRUS OF RABIES WITH REMARKS UPON A NEW
      METHOD.

PMID- 19599559
TI  - Notes and Reviews : WATER PURIFICATION PLANT NOTES.

PMID- 19599560
TI  - PERSONAL HYGIENE NOTES: Dreams as Tokens of Condition.

PMID- 19599561
TI  - MUNICIPAL SANITATION NOTES.

PMID- 19599563
TI  - SANITARY ENGINEERING NOTES.

PMID- 19599562
TI  - A "SCORE SYSTEM" FOR DETERMINING THE REAL RELATIVE IMPORTANCE OF THE DIFFERENT
      INFECTIOUS DISEASES.

PMID- 19599564
TI  - VITAL STATISTICS NOTES.

PMID- 19599565
TI  - SANITATION OF BAKERIES AND RESTAURANT KITCHENS.

PMID- 19599566
TI  - SAVING CHILDREN FROM MILK-BORNE DISEASES.

PMID- 19599567
TI  - Section of Municipal Health Officers: THE TRAINING OF JANITORS IN SANITARY CARE
      OF SCHOOL PREMISES.

PMID- 19599568
TI  - Laboratory Section: ELECTROLYTIC PRODUCTION OF SODIUM HYPOCHLORITE.

PMID- 19599569
TI  - AN EMERGENCY HYPOCHLORITE PLANT.

PMID- 19599570
TI  - A REPORT ON THE HYPOCHLORITE TREATMENT OF WATER AT MINNEAPOLIS.

PMID- 19599572
TI  - Notes and Reviews : MUNICIPAL SANITATION NOTES.

PMID- 19599571
TI  - THE RESISTANCE OF CERTAIN BACTERIA TO CALCIUM HYPOCHLORITE.

PMID- 19599574
TI  - SANITARY ENGINEERING NOTES.

PMID- 19599573
TI  - PERSONAL HYGIENE.

PMID- 19599575
TI  - WATER PURIFICATION PLANT NOTES.

PMID- 19599576
TI  - EDITORIALS: EDUCATIONAL OPPORTUNITIES OF THE HEALTH DEPARTMENT.

PMID- 19599577
TI  - PELLAGRA.

PMID- 19599578
TI  - PREVENTIVE PRINCIPLES IN THE FIELD OF MENTAL MEDICINE.

PMID- 19599579
TI  - THE PREVENTION OF FEEBLE-MINDEDNESS.

PMID- 19599580
TI  - EDITORIALS: DISPOSAL OF GARBAGE AND OTHER REFUSE.

PMID- 19599581
TI  - REPORT OF COMMITTEE ON EDUCATION OF THE PUBLIC AS TO THE COMMUNICABILITY AND
      PREVENTION OF GONORRHOEA AND SYPHILIS.

PMID- 19599582
TI  - A CONSIDERATION OF VENEREAL PROPHYLAXIS IN THE U. S. NAVY FOR THE BENEFIT OF
      PUBLIC HEALTH OFFICIALS.

PMID- 19599583
TI  - VENEREAL DISEASES AMONG SEAMEN OF THE MERCHANT MARINE.

PMID- 19599584
TI  - A PLEA FOR APPLYING THE USUAL METHODS OF PREVENTIVE MEDICINE TO VENEREAL
      DISEASES.

PMID- 19599585
TI  - Laboratory Section: THE BACTERIAL CONTENT OF SEPARATOR CREAM AND SEPARATOR MILK.

PMID- 19599586
TI  - Section of Municipal Health Officers: EPIDEMIOLOGY OF DIPHTHERIA, SCARLET FEVER
      AND MEASLES.

PMID- 19599587
TI  - Section on Vital Statistics: THE IMPORTANCE OF THE REGISTRATION OF MARRIAGE
      CERTIFICATES.

PMID- 19599588
TI  - WATER PURIFICATION PLANT NOTES.

PMID- 19599589
TI  - SPECIAL ARTICLE: A FURTHER CONTRIBUTION TO OUR KNOWLEDGE OF INSECTICIDES.

PMID- 19599590
TI  - ORGANIZATION OF THE PENNSYLVANIA STATE DEPARTMENT OF HEALTH.

PMID- 19599591
TI  - EXECUTIVE METHODS IN PREVENTIVE MEDICINE.

PMID- 19599592
TI  - THE RELATION BETWEEN STATE AND MUNICIPAL BOARDS OF HEALTH.

PMID- 19599594
TI  - REPORT OF THE COMMITTEE ON STANDARD METHODS FOR THE BACTERIOLOGICAL DIAGNOSIS OF
      TUBERCULOSIS.

PMID- 19599593
TI  - Laboratory Section: THE PRESERVATION OF SEWAGE BY THE AID OF CHLOROFORM AND COLD
      STORAGE.

PMID- 19599595
TI  - Section of Municipal Health Officers: REPORT OF COMMITTEE ON FOODS.

PMID- 19599597
TI  - Notes and Reviews : MUNICIPAL SANITATION NOTES.

PMID- 19599596
TI  - Section on Vital Statistics: THE NEED OF EXACT ACCOUNTING FOR STILL-BIRTHS.

PMID- 19599599
TI  - WATER PURIFICATION PLANT NOTES.

PMID- 19599598
TI  - PERSONAL HYGIENE NOTES.

PMID- 19599600
TI  - SANITARY ENGINEERING NOTES.

PMID- 19599602
TI  - THE PREVENTION OF BLINDNESS.

PMID- 19599601
TI  - SPECIAL ARTICLE: SOME EXPERIMENTS UPON THE REMOVAL OF OYSTERS FROM POLLUTED TO
      UNPOLLUTED WATERS.

PMID- 19599603
TI  - THE AMERICAN CIVIC ASSOCIATION AND ITS RELATION TO PUBLIC HEALTH.

PMID- 19599604
TI  - CHILD LABOR AND PUBLIC HEALTH.

PMID- 19599605
TI  - THE AMERICAN MEDICAL ASSOCIATION AND ITS RELATION TO PUBLIC HEALTH WORK.

PMID- 19599607
TI  - THE NATIONAL ASSOCIATION FOR THE STUDY AND PREVENTION OF TUBERCULOSIS.

PMID- 19599606
TI  - THE NATIONAL HOUSING ASSOCIATION AND ITS RELATION TO PUBLIC HEALTH.

PMID- 19599608
TI  - Laboratory Section: HISTORY AND CHEMISTRY OF DISINFECTANTS.

PMID- 19599609
TI  - THE TESTING OF LIQUID DISINFECTANTS.

PMID- 19599610
TI  - SECOND PROGRESS REPORT OF THE COMMITTEE ON STANDARD METHODS FOR THE BACTERIAL
      DIAGNOSIS OF DIPHTHERIA.

PMID- 19599611
TI  - Section of Municipal Health Officers: QUARANTINE OR ISOLATION IN DIPHTHERIA?

PMID- 19599613
TI  - MODERN BOARD OF HEALTH METHODS IN A SMALL TOWN.

PMID- 19599612
TI  - Section on Vital Statistics: REGISTRATION OF BIRTHS.

PMID- 19599614
TI  - MODERN BOARD OF HEALTH METHODS IN SMALL CITIES.

PMID- 19599615
TI  - THE RELATION OF ILLUMINATING GAS TO PUBLIC HEALTH.

PMID- 19599616
TI  - EDITORIALS: IS A SANITARY INSTITUTE FOR AMERICA NEEDED?

PMID- 19599618
TI  - THE CANADIAN COMMISSION OF CONSERVATION AND PUBLIC HEALTH.

PMID- 19599617
TI  - THE PRESENT ORGANIZATION AND WORK FOR THE PROTECTION OF PUBLIC HEALTH IN CANADA.

PMID- 19599619
TI  - ORGANIZATION OF THE SANITARY SERVICE IN THE FEDERAL DISTRICT, TERRITORIES,
      SEAPORTS, AND PRINCIPAL FRONTIER CITIES OF THE MEXICAN REPUBLIC.

PMID- 19599620
TI  - THE PRESENT ORGANIZATION AND WORK FOR THE PROTECTION OF HEALTH IN CUBA.

PMID- 19599621
TI  - STUDIES ON THE SELF-PURIFICATION OF STREAMS.

PMID- 19599622
TI  - Laboratory Section: THE RESISTANCE OF SMALLPOX VACCINE TO THE COAL TAR
      DISINFECTANTS.

PMID- 19599623
TI  - REPORT OF COMMITTEE ON STANDARD METHODS FOR THE DIAGNOSIS OF RABIES.

PMID- 19599624
TI  - Section of Municipal Health Officers: QUARANTINE OR ISOLATION IN SCARLET FEVER,
      WHICH?

PMID- 19599625
TI  - Section on Vital Statistics: TUBERCULOSIS IN IMMIGRANTS.

PMID- 19599626
TI  - VENEREAL DISEASE AND ITS INFLUENCE.

PMID- 19599627
TI  - OPHTHALMIA NEONATORUM: PROGRESS IN PREVENTION.

PMID- 19599628
TI  - WATER PURIFICATION PLANT NOTES.

PMID- 19599629
TI  - PERSONAL HYGIENE.

PMID- 19599630
TI  - ANTI-TYPHOID VACCINATION IN THE AMERICAN ARMY.

PMID- 19599632
TI  - VITAL STATISTICS IN THE PROMOTION OF PUBLIC HEALTH.

PMID- 19599631
TI  - MAYORS AND MUNICIPAL HEALTH.

PMID- 19599633
TI  - Laboratory Section: REPORT OF THE JOINT COMMITTEE ON MAILING INFECTIOUS MATERIAL.

PMID- 19599634
TI  - REPORT OF THE COMMITTEE ON STANDARD METHODS FOR THE BACTERIAL DIAGNOSIS OF
      GLANDERS.

PMID- 19599636
TI  - Section of Municipal Health Officers: GARBAGE RECEPTACLES.

PMID- 19599635
TI  - Section on Vital Statistics: OCCUPATIONAL STATISTICS FOR TUBERCULOSIS IN
      WISCONSIN.

PMID- 19599638
TI  - CLIPPINGS.

PMID- 19599637
TI  - Notes and Reviews : EPIDEMIOLOGY AND PREVENTIVE THERAPEUTICS.

PMID- 19599639
TI  - William Bailey.

PMID- 19599640
TI  - EDITORIALS: THE CHOLERA SITUATION.

PMID- 19599641
TI  - THE CHOLERA SITUATION.

PMID- 19599642
TI  - SPECIAL ARTICLES: THE BACTERIOLOGICAL EXAMINATION OF FECES FOR VIBRIO CHOLERAE.

PMID- 19599643
TI  - A BACTERIOLOGICAL INVESTIGATION OF COMMERCIAL ICE CREAM IN THE CITY OF BOSTON.

PMID- 19599644
TI  - THE RELATION OF UNIVERSITIES TO PUBLIC HEALTH WORK.

PMID- 19599645
TI  - THE ADVANTAGES OF CO-OPERATION BETWEEN STATE BOARDS OF HEALTH AND STATE
      UNIVERSITIES.

PMID- 19599646
TI  - THE RELATION OF THE STATE UNIVERSITY OF NORTH DAKOTA TO THE STATE BOARD OF
      HEALTH.

PMID- 19599647
TI  - THE RELATION OF STATE UNIVERSITIES TO PUBLIC HEALTH WORK.

PMID- 19599649
TI  - HYPOCHLORITE TREATMENT OF PUBLIC WATER SUPPLIES: ITS ADAPTIBILITY AND
      LIMITATIONS.

PMID- 19599648
TI  - THE PURIFICATION OF THE WATER SUPPLY OF RICHMOND, VIRGINIA, BY SEDIMENTATION AND
      COAGULATION, WITHOUT FILTRATION.

PMID- 19599650
TI  - Laboratory Section: PRELIMINARY REPORT OF THE COMMITTEE ON STANDARD METHODS OF
      SHELL-FISH EXAMINATION.

PMID- 19599652
TI  - Section on Vital Statistics: REPORT OF THE COMMITTEE ON UNIFORM TABLES FOR
      STATISTICAL REPORTS AND BULLETINS.

PMID- 19599651
TI  - PRACTICAL TESTS OF CERTAIN FACTORS IN STATE WORK AFFECTING THE ACCURACY OF
      DIPHTHERIA CULTURE DIAGNOSIS.

PMID- 19599653
TI  - SPECIAL ARTICLE: HOW TO GET AND KEEP COMPETENT HEALTH OFFICERS.

PMID- 19599655
TI  - THE VENTILATION OF EMIGRANT SHIPS.

PMID- 19599654
TI  - SOME OF THE LARGER ASPECTS OF THE WORK OF THE METROPOLITAN SEWERAGE COMMISSION OF
      NEW YORK.

PMID- 19599656
TI  - THE CHEMICAL DISINFECTION OF WATER AND SEWAGE; RECENT DEVELOPMENT AND PRESENT
      STATUS.

PMID- 19599657
TI  - Laboratory Section: THE BACTERIOLOGICAL EXAMINATIONS OF SHUCKED AND SHELL
      OYSTERS.

PMID- 19599658
TI  - THE SOURCE, MANUFACTURE AND COMPOSITION OF COMMERCIAL AGAR AGAR.

PMID- 19599659
TI  - SOME RESULTS OBTAINED FROM THE DIGESTION OF SUSPECTED TUBERCULAR SPUTUM.

PMID- 19599660
TI  - Section of Municipal Health Officers: SOME PRELIMINARY NOTES ON THE USE OF
      STREPTOCOCCUS VACCINE AS A MEANS OF PROPHYLAXIS AGAINST SCARLET FEVER.

PMID- 19599661
TI  - THE SCORE CARD SYSTEM OF DAIRY INSPECTION FROM THE NATIONAL STANDPOINT.

PMID- 19599662
TI  - STERILIZING STATIONS IN DAIRY DISTRICTS.

PMID- 19599663
TI  - PASTEURIZATION OF MILK IN THE SEALED AND FINAL PACKAGE.

PMID- 19599664
TI  - WATER PURIFICATION PLANT NOTES.

PMID- 19599666
TI  - YELLOW FEVER HAS DISAPPEARED FROM THE MEXICAN REPUBLIC.

PMID- 19599665
TI  - SPECIAL ARTICLE: AN ISOLATION HOSPITAL BUILT AND OPERATED BY A CITY DEPARTMENT OF
      HEALTH.

PMID- 19599667
TI  - THE EFFECT OF A HIGH TAX ON THE STRUGGLE AGAINST ALCOHOLISM.

PMID- 19599669
TI  - Section of Municipal Health Officers: DIPHTHERIA AND ITS PROPHYLAXIS.

PMID- 19599668
TI  - Laboratory Section: THE INFLUENCE OF STORAGE AND VARIOUS PRESERVATIVES UPON THE
      DISSOLVED OXYGEN IN WATERS.

PMID- 19599670
TI  - SANITARY ENGINEERING NOTES.

PMID- 19599671
TI  - PERSONAL HYGIENE.

PMID- 19599672
TI  - EDITORIALS: PUBLIC HEALTH AND PUBLIC HYSTERIA.

PMID- 19599674
TI  - PRACTICAL MUNICIPAL MILK EXAMINATIONS.

PMID- 19599673
TI  - SPECIAL ARTICLES: EXPERIMENTS IN BOOK DISINFECTION.

PMID- 19599675
TI  - THE PURIFICATION OF WATER BY ANHYDROUS CHLORINE.

PMID- 19599676
TI  - A REVIEW OF PRACTICAL METHODS FOR SUPERVISING THE MILK SUPPLY OF CITIES.

PMID- 19599677
TI  - THE ANTI-RABIC INSTITUTE OF THE BOARD OF HEALTH OF GUADALAJARA.

PMID- 19599678
TI  - Laboratory Section: METHODS OF COLLECTION, TRANSMISSION AND RECORD IN THE ROUTINE
      EXAMINATION OF SPINAL FLUIDS.

PMID- 19599680
TI  - THE QUANTITATIVE DETERMINATION OF B. COLI IN HEAVILY POLLUTED WATERS: A STUDY OF
      THE PRESUMPTIVE TESTS.

PMID- 19599679
TI  - A RESUME OF DIPHTHERIA EXAMINATIONS MADE IN THE BOSTON BOARD OF HEALTH
      BACTERIOLOGICAL LABORATORY IN 1909.

PMID- 19599681
TI  - THE VALUE OF THE ESCULIN TEST.

PMID- 19599682
TI  - THE LABORATORY DIAGNOSIS OF GLANDERS.

PMID- 19599683
TI  - A SUMMARY OF MILK REGULATIONS IN THE UNITED STATES.

PMID- 19599684
TI  - Notes and Reviews : PERSONAL HYGIENE.

PMID- 19599685
TI  - EPIDEMIOLOGY AND PREVENTIVE THERAPEUTICS.

PMID- 19599686
TI  - Dr. Walter Wyman.

PMID- 19599688
TI  - PRACTICAL SUGGESTIONS FOR RAISING THE STANDARD OF MUNICIPAL HEALTH OFFICERS.

PMID- 19599687
TI  - EDITORIALS: NATIONAL HEALTH LEGISLATION.

PMID- 19599691
TI  - PUBLIC HEALTH A PUBLIC SERVICE, NOT A POLITICAL FOOTBALL.

PMID- 19599689
TI  - THE ADVANCE OF PUBLIC HYGIENE IN CUBA.

PMID- 19599690
TI  - THE RELATION OF THE NURSE TO PUBLIC HEALTH PROBLEMS.

PMID- 19599692
TI  - SPECIAL ARTICLES: A COUNTING APPARATUS FOR LITMUS PLATES WITH A COLD COUNTING
      PLATE FOR USE WITH GELATIN PLATES.

PMID- 19599693
TI  - THE REPORT OF THE MINNEAPOLIS VICE COMMISSION.

PMID- 19599694
TI  - METHOD EMPLOYED AT NEW YORK QUARANTINE FOR THE DETECTION OF CHOLERA CARRIERS.

PMID- 19599695
TI  - A SIMPLIFIED BACTERIOLOGICAL TECHNIQUE FOR DETECTING CHOLERA CARRIERS.

PMID- 19599696
TI  - MODERN PRACTICE IN THE DISPOSAL OF REFUSE.

PMID- 19599698
TI  - CONTRIBUTION TO THE STUDY OF BERIBERI.

PMID- 19599697
TI  - A STUDY OF THE VENTILATION OF SLEEPING CARS.

PMID- 19599699
TI  - Laboratory Section: LIVER BROTH.

PMID- 19599701
TI  - Notes and Reviews : PERSONAL HYGIENE.

PMID- 19599700
TI  - CLASSIFICATION OF THE B. COLI GROUP.

PMID- 19599702
TI  - Sewage and Sewage Disposal: With a Description of the Sewage Works at Worcester,
      Mass.

PMID- 19599704
TI  - Rabies: Its Prevalence and Suppression.

PMID- 19599703
TI  - The Disposal of Garbage.

PMID- 19599705
TI  - Progress in Ventilating School-Houses.

PMID- 19599706
TI  - Rabies: With an Account of Pasteur's Work and Methods.

PMID- 19599707
TI  - Observations on the Suppression of Infectious Diseases.

PMID- 19599708
TI  - The Old Oaken Bucket.

PMID- 19599709
TI  - The Boston Main Drainage Works.

PMID- 19599711
TI  - "The Simonin Process for Treatment of Infected Articles.".

PMID- 19599710
TI  - The Metropolitan System of Sewerage: Its Present Status and Condition.

PMID- 19599712
TI  - The Destruction of Town Waste by Fire.

PMID- 19599714
TI  - Warren Ventilating and Sanitary Construction.

PMID- 19599713
TI  - School-Room Ventilation.

PMID- 19599715
TI  - The Value of Disinfectants.

PMID- 19599716
TI  - Pure Water.

PMID- 19599717
TI  - The Blue Hill Mineral Spring.

PMID- 19599718
TI  - The Davidson Ventilating Fan.

PMID- 19599719
TI  - Nobscot Mountain Spring Water.

PMID- 19599720
TI  - A Plain Right and a Plain Duty.

PMID- 19599722
TI  - Address of Walter H. Chapin, M. D.

PMID- 19599721
TI  - Address of Prof. W. T. Sedgwick.

PMID- 19599723
TI  - Certain Needed Legislation.

PMID- 19599724
TI  - Index Value of Curves Representing Percentage of Deaths from Phthisis in Deaths
      from All Causes: Omitted from Report of a Previous Meeting.

PMID- 19599725
TI  - English Regulations for Closing Schools by Order of Boards of Health.

PMID- 19599726
TI  - Death Certificates.

PMID- 19599727
TI  - Anti-Toxine.

PMID- 19599728
TI  - Physicians' Return of Death: Omitted from Report of October, 1894, Quarterly
      Meeting.

PMID- 19599729
TI  - Progress of Plumbing.

PMID- 19599730
TI  - Sewage Filtration and Municipal Sanitation.

PMID- 19599731
TI  - Purification of Sewage-Polluted Waters by Sand Filtration.

PMID- 19599733
TI  - The Disinfection of Farm Buildings, Stables, and Similar Places.

PMID- 19599732
TI  - Disease in Carpetings: A Method which Disinfects, Cleanses, and does not Harm.

PMID- 19599735
TI  - Report of the Committee on Certificates of Death.

PMID- 19599734
TI  - The Best Methods of Garbage Disposal for Large and Small Cities.

PMID- 19599736
TI  - Efficient Disinfection.

PMID- 19599738
TI  - The Authority of Local Boards of Health over Public Institutions.

PMID- 19599737
TI  - Culture Diagnosis of Diphtheria.

PMID- 19599739
TI  - On the Protection of Public Milk Supplies from Pollution.

PMID- 19599740
TI  - The Disposal of Garbage.

PMID- 19599741
TI  - Remarks, "Lamp and Generator for the Production of Formic Aldehyde.".

PMID- 19599742
TI  - Report of the Committee.

PMID- 19599743
TI  - Bacteria and Acidity of the Milk Supply of Boston: A Familiar Talk.

PMID- 19599744
TI  - Experiments with Formaldehyde Gas as a Disinfectant.

PMID- 19599745
TI  - The Use of Formaldehyde in House Disinfection.

PMID- 19599746
TI  - Proper Isolation of Infectious Diseases.

PMID- 19599747
TI  - A Model Dairy Farm.

PMID- 19599748
TI  - Quarantine Department, City of Boston.

PMID- 19599749
TI  - On the Regulation Requiring Two Consecutive Negative Cultures for the Release of
      Diphtheria Cases.

PMID- 19599750
TI  - Disposal of Sewage of Small Villages, Public Institutions, Factories, etc.

PMID- 19599751
TI  - Infant Mortality in Massachusetts.

PMID- 19599752
TI  - Advantages of Hospitals for Infectious Diseases and of Anti-Toxine in Diphtheria.

PMID- 19599753
TI  - The Branching Form of Bacillus Diphtheriae as an Aid in Bacteriological
      Diagnosis.

PMID- 19599754
TI  - Rabies in Boston.

PMID- 19599755
TI  - The Refuse Disposal Plant of Boston.

PMID- 19599756
TI  - A Simple and Accurate Method of Carbon Dioxide Determination, with Demonstration.

PMID- 19599757
TI  - Anti-Rabic Institutions.

PMID- 19599758
TI  - The Inspection of Milk.

PMID- 19599759
TI  - Anti-Rabic Institution for Massachusetts.

PMID- 19599760
TI  - On the Presence of the Typhoid Bacillus in the Urine, and its Relation to the
      Public Health.

PMID- 19599761
TI  - Some Questions Relating to the Bacteriological Diagnosis of Diphtheria.

PMID- 19599762
TI  - The Incubation and Infective Periods of Some of the Infectious Disease.

PMID- 19599763
TI  - Address of Welcome by Mr. Charles C. Cook, Chairman of the Board of Selectmen.

PMID- 19599764
TI  - Rapid Diagnosis of Diphtheria by Direct Swab Examinations.

PMID- 19599765
TI  - Food Infection by the Typhoid Bacillus.

PMID- 19599766
TI  - Address of Mr. Keith.

PMID- 19599767
TI  - A Diphtheria Outbreak Believed to be due to Infected Milk.

PMID- 19599768
TI  - Lead Poisoning as a Public Health Question.

PMID- 19599769
TI  - Prize Essay.

PMID- 19599770
TI  - Service Pipes for Water Supplies Which Corrode Lead and Other Metals.

PMID- 19599772
TI  - Glanders.

PMID- 19599771
TI  - The Cesspool.

PMID- 19599773
TI  - The Necessity for More Thorough Inspection of Sanitary Conditions in
      Massachusetts.

PMID- 19599774
TI  - The Results of One Year's Use of the Swab Method in the Rapid Diagnosis of
      Diphtheria.

PMID- 19599775
TI  - Address of the Chairman of the Committee on Diphtheria Bacilli in Well Persons.

PMID- 19599776
TI  - On the Drainage, Reclamation, and Sanitary Improvement of Certain Marsh Lands in
      the Immediate Vicinity of Boston.

PMID- 19599777
TI  - Report of Committee on Diphtheria Bacilli in Well Persons.

PMID- 19599778
TI  - Address by Mayor O'Connell of Worcester.

PMID- 19599779
TI  - Results Accomplished at Worcester Isolation Hospital.

PMID- 19599780
TI  - The Sewage Disposal Works at Worcester, Massachusetts.

PMID- 19599781
TI  - Report of the Committee on "Diphtheria Bacilli in Well Persons" in Regard to
      Teaching Cleanliness among School-Children.

PMID- 19599782
TI  - An Apparent Case of Diphtherial Infection from Well Persons Carrying Diphtheria
      Bacilli.

PMID- 19599783
TI  - Survival of Typhoid Bacilli in Bodies of Cooked Shell-Fish.

PMID- 19599784
TI  - The Etiology of Malaria, with Special Reference to the Mosquito as an
      Intermediate Host.

PMID- 19599785
TI  - The Purification of Water by Freezing.

PMID- 19599786
TI  - Small-Pox and Vaccination.

PMID- 19599787
TI  - Remarks on "Opposition to Vaccination.".

PMID- 19599788
TI  - The Result of Imperfect Combustion of Fuel.

PMID- 19599789
TI  - Report on Diphtheria Bacilli in Well Persons.

PMID- 19599790
TI  - Sanitation in the Schools.

PMID- 19599791
TI  - Sanitary Inspection.

PMID- 19599793
TI  - A Note on Paratyphoid Fever from the Public Health Standpoint.

PMID- 19599792
TI  - Abatement of the Mosquito Nuisance in Brookline.

PMID- 19599794
TI  - The Action of Vaporized Formaldehyde and Vaporized Carbolic Acid as Gaseous
      Disinfectants.

PMID- 19599795
TI  - The Present Outbreak of Foot-and-Mouth Disease in the New England States.

PMID- 19599796
TI  - Educational Sanitary Inspection.

PMID- 19599798
TI  - The Recent Smallpox Epidemic in Massachusetts.

PMID- 19599797
TI  - Inspection of Tenement Houses.

PMID- 19599799
TI  - The Milk Supply of Large Cities.

PMID- 19599800
TI  - A Comparison of Some of the More Common Liquid Disinfectants.

PMID- 19599801
TI  - The Mosquito Nuisance and How to Deal with it.

PMID- 19599802
TI  - The Etiology of Dysentery.

PMID- 19599803
TI  - The Metropolitan Water Supply.

PMID- 19599805
TI  - The Typhoid Fever Epidemic at Butler, Pa.

PMID- 19599804
TI  - The Etiology and Treatment of the Summer Diarrhoea in Infants.

PMID- 19599806
TI  - Some of the Ways in Which Infection is Disseminated.

PMID- 19599807
TI  - The Physiologist, Bayliss, vs. Coleridge, the Antivivisectionist.

PMID- 19599808
TI  - Sources Effects and Prevention of Dirty Milk.

PMID- 19599809
TI  - Mr. Coleridge in a New Role.

PMID- 19599810
TI  - The Efficiency of Public Prophylaxis against Tuberculosis.

PMID- 19599811
TI  - The Transmission of Infection by Means of Footwear.

PMID- 19599813
TI  - The United States Society for the Study of Tuberculosis.

PMID- 19599812
TI  - Sanitary Engineering Notes.

PMID- 19599814
TI  - Uniform Standards in Public Health Administration.

PMID- 19599815
TI  - Medical Inspection of Schools.

PMID- 19599817
TI  - The Sanitary Dangers of Certain Occupations.

PMID- 19599816
TI  - Typhoid Fever Epidemic at Columbus, O.

PMID- 19599819
TI  - Copper Sulphate vs. Algae.

PMID- 19599818
TI  - Scarlet Fever Isolation.

PMID- 19599820
TI  - A Paradox in the Death-Rate in Various Districts in New York.

PMID- 19599821
TI  - Sanitary Engineering.

PMID- 19599822
TI  - Preventive Therapeutics.

PMID- 19599823
TI  - Veterinary Sanitation.

PMID- 19599824
TI  - Municipal Sanitation.

PMID- 19599826
TI  - The Fate of Typhoid Bacilli in Beer.

PMID- 19599825
TI  - Milk and Foods.

PMID- 19599827
TI  - Meat Poisoning and Paratyphoid.

PMID- 19599828
TI  - Laboratory Work.

PMID- 19599829
TI  - Leprosy.

PMID- 19599830
TI  - The Present Status of Mortality Registration in the United States.

PMID- 19599831
TI  - The Value of Restrictive Measures in the Contagious Diseases.

PMID- 19599832
TI  - Dr. Samuel Warren Abbott.

PMID- 19599834
TI  - Bacterial Counts of Boston's Milk Supply.

PMID- 19599833
TI  - The New Laboratory of the Massachusetts State Board of Health for the Preparation
      of Diphtheria Antitoxin and Vaccine.

PMID- 19599835
TI  - Two Recent Outbreaks of Typhoid Fever in Boston.

PMID- 19599836
TI  - Milk and Foods.

PMID- 19599837
TI  - Preventive Therapeutics.

PMID- 19599838
TI  - Veterinary Sanitation.

PMID- 19599839
TI  - Municipal Sanitation.

PMID- 19599840
TI  - Vital Statistics.

PMID- 19599841
TI  - Canadian Notes.

PMID- 19599842
TI  - On the Limitations and Modifying Conditions of Human Longevity, the Basis of
      Sanitary Work.

PMID- 19599844
TI  - On the Relative Influence of City and Country Life on Morality, Health,
      Fecundity, Longevity, and Mortality.

PMID- 19599843
TI  - Remarks upon One of the First Principles of Hospital Hygiene.

PMID- 19599845
TI  - Sanitary Science in its Relations to Public Instruction.

PMID- 19599846
TI  - A Report upon Sanitary Relations to Health Principles of Architecture.

PMID- 19599847
TI  - Report upon "Non-Periodic Changes of Heat as an Element in Sanitary
      Climatology.".

PMID- 19599848
TI  - Relations of Water to the Propagation of Fever.

PMID- 19599849
TI  - Report on the Practical Lessons of the Recent Prevalence of Small-Pox, with
      Reference to its Prevention in the Future.

PMID- 19599850
TI  - The Relations of Race and Nationality to Mortality in the United States.

PMID- 19599852
TI  - Report of Cholera in New Orleans.

PMID- 19599851
TI  - Plan of a Hospital and Cleansing Establishment for the Treatment of Cholera, and
      Guarding against its Introduction at Ports and Places of Entrance.

PMID- 19599853
TI  - An Account of the Epidemic of Cholera during the Summer of 1873, in Eighteen
      Counties of the State of Kentucky.

PMID- 19599855
TI  - Cholera in Chattanooga, Tenn., and Cities South of Nashville, during the Summer
      of 1873.

PMID- 19599854
TI  - Report upon the Course of Cholera through Two Hundred Towns and Cities in the
      Mississippi Valley.

PMID- 19599856
TI  - Cholera in Little Rock, Arkansas.

PMID- 19599857
TI  - Cholera as it Prevailed in Chicago, in 1873.

PMID- 19599858
TI  - Note upon the Results of Microscopic Examination of the Choleraic Discharges.

PMID- 19599859
TI  - Cholera in Wheeling, West Va., in 1873.

PMID- 19599860
TI  - Report upon Epidemic Cholera as it Appeared at Jonesborough, Tenn.

PMID- 19599861
TI  - Cholera in Knoxville, Tenn., and Vicinity.

PMID- 19599862
TI  - Cholera in Cincinnati, Ohio.

PMID- 19599863
TI  - Report on Asiatic Cholera.

PMID- 19599865
TI  - What We can Do against Cholera: Practical Instructions concerning what to Do to
      Prevent an Epidemic as Well as How to Guard against it during its Prevalence.

PMID- 19599864
TI  - Local Measures of Prevention and Relief to be Adopted during the Prevalence of
      Epidemic Cholera.

PMID- 19599866
TI  - The Origin and Spread of Asiatic or Bengal Cholera.

PMID- 19599867
TI  - Practical Conclusions concerning Cholera. Evidence respecting Causes and
      Preventive Measures.

PMID- 19599868
TI  - The Distribution and Natural History of Yellow Fever as it has Occurred at
      Different Times in the United States.

PMID- 19599870
TI  - A Report on Yellow Fever as it Appeared in Memphis, Tenn., in 1873.

PMID- 19599869
TI  - Perfection of Structure in the Human Body, as a Leading Element of Hygiene.

PMID- 19599871
TI  - An Account of Yellow Fever as it Prevailed in Mobile and Vicinity in 1873.

PMID- 19599872
TI  - What to Do against Yellow Fever.

PMID- 19599873
TI  - General Principles Affecting the Organization and Practice of Quarantine.

PMID- 19599874
TI  - Principles and Practice of Quarantine at the Port of Charleston, S. C.

PMID- 19599875
TI  - Some Account of Yellow Fever as it Appeared in New Orleans in 1873.

PMID- 19599876
TI  - Effectual External Regulations without Delay to Commerce.

PMID- 19599878
TI  - Sailors as Propagators of Disease: Abstract of a Paper Entitled "The Hygiene of
      the Forecastle.".

PMID- 19599877
TI  - Some Defects in the Immigration Service: Suggestions of Remedy therefor, with
      Reference to the Sanitary Interests of the Country.

PMID- 19599879
TI  - A Report upon the Sanitary Care and Utilization of the Refuse of Cities.

PMID- 19599880
TI  - Report on Disinfection and Disinfectants.

PMID- 19599881
TI  - The General Causes of Disease.

PMID- 19599883
TI  - A Report on a Uniform System of Registration of Causes of Death throughout the
      United States.

PMID- 19599882
TI  - General Health Laws and Local Ordinances, Considered with Reference to State and
      Local Sanitary Organization.

PMID- 19599884
TI  - The Need of Sanitary Organization in Villages and Rural Districts.

PMID- 19599885
TI  - Boards of Health in the United States.

PMID- 19599886
TI  - A Report upon the Necessity for a National Sanitary Bureau.

PMID- 19599887
TI  - Report upon the Sanitary Chemistry of Waters, and Suggestions with Regard to the
      Selection of the Water Supply of Towns and Cities.

PMID- 19599888
TI  - The Longevity of Brain-Workers.

PMID- 19599889
TI  - The Germ Theory of Disease and its Relations to Hygiene.

PMID- 19599890
TI  - History and Course of the Epizootic among Horses upon the North American
      Continent in 1872-73.

PMID- 19599891
TI  - The Leading Public Health Questions in the United States.

PMID- 19599892
TI  - Health of Tenement Populations,-Sanitary Requirements of their Dwellings.

PMID- 19599893
TI  - Report on the Death-Rate of Each Sex in Michigan, and a Comparison with Dr.
      Farr's Life-Tables of Healthy Districts of England.

PMID- 19599894
TI  - Influence of the High Altitudes and Climate of the Table-Land Country of the
      Rocky Mountain Region upon Health and Disease.

PMID- 19599895
TI  - Abstract of Special Reports by Army Medical Officers on the Effect of Mountain
      Climates upon Health.

PMID- 19599896
TI  - Report on the Public Health Service in the Principal Cities, and Sanitary Works
      in the United States.

PMID- 19599897
TI  - The Reciprocal Relations of an Efficient Public Health Service and the Highest
      Educational Qualifications of the Medical Profession.

PMID- 19599898
TI  - Health and the Higher Culture.

PMID- 19599899
TI  - Infant Mortality in Cities.

PMID- 19599900
TI  - Influence of Hereditary Defects on Health. Their Prevention and Eradication.

PMID- 19599901
TI  - Hereditary Entailments in Domestic Animals and in the Human Family.

PMID- 19599902
TI  - Relations of Excessive Use of Alcoholic Drinks to the Public Health.

PMID- 19599903
TI  - Alcoholic Drinks in Relation to Life-Insurance.

PMID- 19599904
TI  - Perils of the School-Room.

PMID- 19599905
TI  - Certain Relations of Geology to the Water-Supplies of the Country.

PMID- 19599906
TI  - Building-Ground and Dwelling-Houses in their Relations to Health.

PMID- 19599907
TI  - Sanitary Principles in Home Architecture.

PMID- 19599908
TI  - Principles and Practice of Drainage and Sewerage, in connection with Water
      Supplies.

PMID- 19599909
TI  - The Drowned Lands of Orange County, N. Y., and Sussex County, N. J.-their
      Drainage.

PMID- 19599910
TI  - Geological and Sanitary Relations of Drainage and Water-Supply in North Carolina.

PMID- 19599912
TI  - Sewer-Gas as a Cause of Diphtheria and Typho-Malarial Diseases.

PMID- 19599911
TI  - Soil Drainage and Atmospheric Humidity.

PMID- 19599913
TI  - A Plea for Sanitary Engineering.

PMID- 19599914
TI  - The Sanitary Relations of Hospitals.

PMID- 19599915
TI  - Notes on Hospital Construction.

PMID- 19599917
TI  - Hospitalism and Hospital Construction.

PMID- 19599916
TI  - Location, Plan, and Management of Hospitals.

PMID- 19599918
TI  - The Factors of Disease and Death after Injuries, Parturition, and Surgical
      Operations.

PMID- 19599919
TI  - Report of Committee on a Sanitary Survey of the United States.

PMID- 19599920
TI  - Does Small-Pox Become Epidemic, or Spread Only by its Own Contagion?

PMID- 19599921
TI  - Cost of a Great Epidemic to a Great City.

PMID- 19599922
TI  - Advantages of Small Hospitals or Infirmaries for Manufacturing and Mining Towns.

PMID- 19599923
TI  - Relations of Syphilis to the Public Health.

PMID- 19599925
TI  - Yellow Fever in Pensacola, Fla., in 1873-4-5.

PMID- 19599924
TI  - Report on Malignant Anthrax in Herds and Malignant Pustule in Man, (on the
      Wadsworth Estate).

PMID- 19599926
TI  - Yellow Fever on the Dry Tortugas.

PMID- 19599927
TI  - Pharmacy in its Sanitary Relations.

PMID- 19599928
TI  - Essential Conditions of Good Sanitary Administration.

PMID- 19599930
TI  - Record of Proceedings and Papers.

PMID- 19599929
TI  - A Sanitary View of the Question,-"Am I my Brother's Keeper?".

PMID- 19599932
TI  - The Gathering, Packing, and and Free Marketing of Fresh Vegetables and Fruits.

PMID- 19599931
TI  - Report on Sanitary Conditions of Watering-Places.

PMID- 19599933
TI  - Report on Poisons as Insecticides in Agriculture, and Tests of their Effects on
      Food-Vegetables.

PMID- 19599934
TI  - Influence of City Life and Occupations in Developing Pulmonary Consumption.

PMID- 19599935
TI  - Food in its Relations to Personal and Public Health.

PMID- 19599936
TI  - Relations of Topographical Surveys and Maps to Public Health Studies.

PMID- 19599937
TI  - Report on the Preparation of a Plan for a Sanitary Survey of the United States.

PMID- 19599938
TI  - Water-Supplies for Large Institutions and Small Communities.

PMID- 19599939
TI  - The Sanitary Appointments and Outfitting of Dwelling-Houses.

PMID- 19599940
TI  - The Sanitary Condition of Country-Houses and Grounds.

PMID- 19599941
TI  - Laws, Provisions, and Methods for Securing the Benefits of General Vaccination
      throughout the Country.

PMID- 19599942
TI  - Disinfection in Yellow Fever, as Practiced in New Orleans: Evidence of its
      Efficacy.

PMID- 19599943
TI  - Sanitary Regulations Relating to Abattoirs.

PMID- 19599945
TI  - Ancient and Modern Hygiene Contrasted.-Influence of Civilization on the Duration
      of Life.

PMID- 19599944
TI  - Scarlatina in Baltimore and Belair, Md.

PMID- 19599946
TI  - Health Interests in the Preservation of Certain Primeval Forests and the
      Cultivation of Trees.

PMID- 19599947
TI  - Privy Vaults and Cesspools.

PMID- 19599948
TI  - Summer Resorts for the Debilitated Children of our Cities.

PMID- 19599950
TI  - The Gases of Decay and the Harm they Cause in Dwellings, etc.

PMID- 19599949
TI  - A Report on Methods of Ventilation.

PMID- 19599951
TI  - A New Profession in the Service of Hygiene.

PMID- 19599952
TI  - The Popularization of Sanitary Science in Schools.

PMID- 19599953
TI  - Florida as a Health Resort.

PMID- 19599955
TI  - Expert Testimony and the Public Service of Experts.

PMID- 19599956
TI  - Expert Supervision in Construction of Public Institutions.

PMID- 19599954
TI  - Abattoirs and the Slaughtering Business in New York.

PMID- 19599957
TI  - Rights, Duties and Privileges of the Community in Relation to those of the
      Individual in Regard to Health.

PMID- 19599959
TI  - Illuminating Gas in its Relations to Health.

PMID- 19599958
TI  - The Influence of Private Dwellings and other Habitations on Public Hygiene: The
      Relations of Sanitary Authority to them.

PMID- 19599960
TI  - Sanitary Requirements in Factories.-Injurious Effects of Cotton Factories upon
      the Health of Operatives.

PMID- 19599961
TI  - The Safety of Ships and of those who Travel in them.

PMID- 19599963
TI  - Marine Hygiene on Board Passenger Vessels: Practical Conclusions Based upon the
      Experience of Ocean Lines in Communication with New York.

PMID- 19599962
TI  - The Need of Sanitary Reform in Ship-Life.

PMID- 19599964
TI  - Public Economy of Sanitary Measures: An Address of Welcome.

PMID- 19599965
TI  - Air and Moisture on Shipboard: A Fragment of Applied Physiology.

PMID- 19599966
TI  - Public Holidays and Public Health.

PMID- 19599967
TI  - Sanitary Safety in Railway Traveling. Suggestions in the Interest of Travelers
      and Carriers.

PMID- 19599969
TI  - Report on Plans for Complete and Authentic Records of Deaths and the Causes of
      Death in the United States.

PMID- 19599968
TI  - Sanitary Problems: The Proper and Rational Method in which Municipal Boards of
      Health should be Organized.

PMID- 19599970
TI  - Address of Welcome.

PMID- 19599971
TI  - Address.

PMID- 19599972
TI  - Significance of the Recent Epidemic. Duties of the American Public Health
      Association.

PMID- 19599973
TI  - Address.

PMID- 19599974
TI  - An Address on the Objects of the Association, and its Claims upon the People for
      Sympathy and Support.

PMID- 19599975
TI  - How to Study an Epidemic.

PMID- 19599976
TI  - The Drainage and Sewerage of Chicago.

PMID- 19599977
TI  - History of the Importation of Yellow Fever into the United States, from 1693 to
      1878.

PMID- 19599979
TI  - Yellow Fever as it Existed in Chattanooga, Tenn. Its Origin, Progress, and the
      Probable Remedy for its Abatement in the Future.

PMID- 19599978
TI  - Report of the Delegation from the Mississippi State Board of Health to the
      American Public Health Association.

PMID- 19599980
TI  - The Quarantine at Little Rock, Arkansas, during August, September, and October,
      1878, against the Yellow Fever Epidemic in Memphis and the Mississippi Valley.

PMID- 19599981
TI  - On the Geographical Element in the Etiology of Yellow Fever, and its Bearing upon
      Prevention.

PMID- 19599982
TI  - The Epidemic of 1839.

PMID- 19599983
TI  - Is Efficient Quarantine Possible or Practicable?

PMID- 19599984
TI  - Memorandum concerning the Refugee Cases of Yellow Fever in Philadelphia, 1878.

PMID- 19599985
TI  - Report on the Yellow Fever in Nashville, Tenn., September and October, 1878.

PMID- 19599987
TI  - A Study of the Yellow Fever Epidemic of 1876, as it Affected the State of
      Georgia.

PMID- 19599986
TI  - History of the Epidemic in Baltimore in 1876.

PMID- 19599988
TI  - Report on a Sanitary Survey of the United States.

PMID- 19599990
TI  - Propositions Relative to the Etiology of Yellow Fever.

PMID- 19599989
TI  - Views on the Subject of Prevention of Yellow Fever.

PMID- 19599991
TI  - Epidemic of 1864.

PMID- 19599992
TI  - Disinfection of Sewers by Ozone.

PMID- 19599993
TI  - The Prophylactic Treatment of Individuals as a Means of Preventing Epidemics of
      Yellow Fever or other Infective Diseases.

PMID- 19599994
TI  - The Sanitary Problems of Chicago: An Introductory Discourse.

PMID- 19599995
TI  - Note concerning the Omitted Papers, Reports, and Discussions Relating to Work of
      the Commission to Investigate Yellow Fever.

PMID- 19599997
TI  - Practical Suggestions concerning Tree-Planting for Sanitary Effects.

PMID- 19599996
TI  - The Sanitary Value of Forests.

PMID- 19599998
TI  - Hygiene at Amherst College: Experience of the Department of Physical Education
      and Hygiene in Amherst College for the past Sixteen Years.

PMID- 19599999
TI  - Hygiene and Higher Education.

PMID- 19600000
TI  - The Removal and Utilization of Domestic Excreta.

PMID- 19600001
TI  - The Work of Hygiene in the Education of Children in the Common Schools, and in
      the Families and Society in which they Live.

PMID- 19600002
TI  - A Review of the Present State of Exact Knowledge regarding the Causation of
      Epidemic Infectious Diseases.

PMID- 19600003
TI  - Annual Address.

PMID- 19600004
TI  - How to Deal with a First Case and Early Cases of Yellow Fever, when, in Spite of
      Precautions, it has Made its Appearance.

PMID- 19600005
TI  - Yellow Fever Epidemic in Memphis, 1879.

PMID- 19600006
TI  - Quarantine, and its Results in the State of Arkansas, 1879.

PMID- 19600007
TI  - The Inefficiency of Quarantine in the State of Arkansas during the Year 1879.

PMID- 19600008
TI  - The Yellow Fever Quarantine of the Future, as Organized upon the Portability of
      Atmospheric Germs and upon the Non-Contagiousness of the Disease.

PMID- 19600009
TI  - International Quarantine.

PMID- 19600010
TI  - Etiology of Yellow Fever, with Remarks on Quarantine.

PMID- 19600011
TI  - Camps; Depopulation of Memphis; Epidemics, 1878 and 1879.

PMID- 19600013
TI  - Method Introduced by the Auxiliary Sanitary Association for Disposing of the
      Garbage of New Orleans.

PMID- 19600012
TI  - City Scavengering in Boston.

PMID- 19600015
TI  - Underground Sewers.

PMID- 19600014
TI  - The Sewerage and Drainage of Cities.

PMID- 19600016
TI  - Remarks upon Necessity for the Filing in a Public Office of Plans and Statements
      about Certain Matters of House Construction. Upon the Study of the Origin of
      Contagious Diseases, and the Liability to Error in this Direction. Upon the
      Necessity for Uniformity in the Publication of Vital Statistics.

PMID- 19600017
TI  - On the Protection of the Innocent and Helpless Members of the Community from
      Venereal Diseases and their Consequences.

PMID- 19600018
TI  - On Rotting Wood.

PMID- 19600019
TI  - Action of Vegetable Acids on Tin.

PMID- 19600021
TI  - Cotton as a Fomite.

PMID- 19600020
TI  - On Post Mortem Examinations and their Relations to Public Health.

PMID- 19600023
TI  - History of the Association.

PMID- 19600022
TI  - May not Yellow Fever Originate in the United States?: An Etiological Study of the
      Epidemic at Savannah in 1876.

PMID- 19600024
TI  - The President's Address.

PMID- 19600026
TI  - Addresses of Gov. Louis A. Wiltz of Louisiana.

PMID- 19600025
TI  - The Relations of Schools to Diphtheria, etc.

PMID- 19600027
TI  - The Domestic Pestilences Viewed with Reference to the Sanitary Warfare against
      them.

PMID- 19600028
TI  - Dengue.

PMID- 19600029
TI  - Address of Hon. I. W. Patton, Mayor of New Orleans.

PMID- 19600030
TI  - Address of Dr. J. P. Davidson, Vice-President Louisiana State Medical Society.

PMID- 19600031
TI  - The Relations of Certain Filth Diseases to Cold Weather.

PMID- 19600032
TI  - The Condition of the Mexican Population of Western Texas in Relation to Public
      Health.

PMID- 19600033
TI  - A Brief Synopsis of "Break-Bone" or Dengue Fever as prevailing in Charleston,
      S.C., in the Summer of 1880.

PMID- 19600034
TI  - Dengue or Dandy Fever.

PMID- 19600035
TI  - The Hygiene of Emigrant Ships.

PMID- 19600036
TI  - The Prevention of Certain Contagious Diseases by Local Boards of Health.

PMID- 19600037
TI  - Municipal Sanitation as Practised in Mobile for Preventing the Spread of Yellow
      Fever.

PMID- 19600038
TI  - The Results of Attempting to Check the Spread of Small-Pox in Chicago.

PMID- 19600039
TI  - Memphis Sanitation and Quarantine 1879 and 1880.

PMID- 19600041
TI  - Sanitary Protection in Newport.

PMID- 19600040
TI  - The Sanitary Association of Lynn, Mass.

PMID- 19600043
TI  - How Abattoirs Improve the Sanitary Condition of Cities.

PMID- 19600042
TI  - Abattoirs.

PMID- 19600044
TI  - Disease among Texas Cattle.

PMID- 19600046
TI  - The Value of Sanitation from an Economic Stand-Point.

PMID- 19600045
TI  - Sanitation and Education.

PMID- 19600048
TI  - What the State Owes the People.

PMID- 19600047
TI  - A Consideration of the Objections Urged by Some Evolutionists against Sanitary
      Laws, etc.

PMID- 19600049
TI  - The Tenement-House Reform in the City of New York.

PMID- 19600050
TI  - The Disposal of Our Dead.

PMID- 19600051
TI  - Storm-Water and House-Drainage in Sewers.

PMID- 19600053
TI  - Some Suggestions in Regard to Sanitation and the Drainage of Small Cities and
      Towns.

PMID- 19600052
TI  - Strom-Water in Town Sewerage.

PMID- 19600054
TI  - On the Action of Muddy Water on Sewage.

PMID- 19600056
TI  - Numerical Sanitation: A Calculus of Subsoil Drainage in New Orleans.

PMID- 19600055
TI  - The Sanitary Urgency of the Florida Ship-Canal.

PMID- 19600057
TI  - Yellow-Fever Recognition and Isolation.

PMID- 19600058
TI  - Yellow Fever and Quarantine.

PMID- 19600059
TI  - A New Method of Investigation into the Causes of Yellow Fever upon the Basis of
      Similar Densities.

PMID- 19600060
TI  - Report on Yellow Fever in Key West, Fla., in 1880.

PMID- 19600061
TI  - Nature, Cause, Extension, and Relations of Dengue or Break-Bone Fever in South
      Carolina, Summer of 1880; also Contrasted with Yellow and Malarial Fevers.

PMID- 19600062
TI  - The Report of the Advisory Council on National Sanitary Legislation.

PMID- 19600063
TI  - The Report of the Committee on the Prevention of Venereal Diseases.

PMID- 19600064
TI  - The Report of the New Orleans Medical and Surgical Association on Propositions
      Submitted by the Executive Committee upon Questions Relating to Prevention of the
      Spread of Diphtheria, Scarlet Fever, Yellow Fever, Measles, Small-Pox, etc.

PMID- 19600065
TI  - The Management of Contagious and Infectious Diseases in Milwaukee.

PMID- 19600066
TI  - Our Present and Our Needed Knowledge of Epidemics.

PMID- 19600067
TI  - The President's Address.

PMID- 19600069
TI  - Disease among Texas Cattle.

PMID- 19600068
TI  - Address of Capt. George A. Mercer, of Savannah.

PMID- 19600071
TI  - A Report of the Examination of Hogs at the New Orleans Abattoir, with Reference
      to Trichinae Spiralis.

PMID- 19600070
TI  - Address of Dr. Richard J. Nunn, of Georgia.

PMID- 19600072
TI  - Trichinae Spiralis: Its History, Pathology, and Diagnosis.

PMID- 19600074
TI  - The Contagious Diseases of Domestic Animals.

PMID- 19600073
TI  - Report of Examinations for Trichinae, of Hogs Killed at San Antonio, Texas.

PMID- 19600076
TI  - Malaria in New England.

PMID- 19600075
TI  - The Rise and Progress of International Hygiene.

PMID- 19600077
TI  - Malaria in Connecticut.

PMID- 19600078
TI  - Observations on the Potomac Marshes at Washington, D. C.

PMID- 19600079
TI  - The Yellow Fever Epidemic at New Orleans in 1878.

PMID- 19600081
TI  - Memorandum of Probable Cause of an Epidemic of Diarrhoeal Diseases in Buffalo, N.
      Y., in 1881.

PMID- 19600082
TI  - The Atmospheric Element in Epidemics.

PMID- 19600080
TI  - Practical Experiences in Regard to the Infection of Vessels with Yellow Fever at
      Havana.

PMID- 19600084
TI  - The Control of Defective Vision on Land and Sea.

PMID- 19600083
TI  - Railroad Sanitation, its Objects and Advantages.

PMID- 19600085
TI  - Effects of Tobacco on Youths.

PMID- 19600086
TI  - School Hygiene.

PMID- 19600087
TI  - Suicides in New York City.

PMID- 19600089
TI  - Inside Sources of Disease.

PMID- 19600088
TI  - The Comparative Vital Movement of the White and Colored Races in the United
      States.

PMID- 19600091
TI  - Impure Water and its Dangers.

PMID- 19600090
TI  - "The Kankakee": A Sanitary Problem of Indiana.

PMID- 19600092
TI  - Scarlet Fever in Charleston, S. C.

PMID- 19600093
TI  - The Sunstroke Epidemic of Cincinnati, Ohio, during the Summer of 1881.

PMID- 19600094
TI  - Two Suggestions concerning Healthy Buildings.

PMID- 19600096
TI  - National and International Sanitary Jurisprudence.

PMID- 19600095
TI  - The Disposal of the Dead.

PMID- 19600097
TI  - What the People Owe to the State.

PMID- 19600098
TI  - Health, the True Nobility.

PMID- 19600099
TI  - The Sanitary Significance of the International Medical Congress of 1881.

PMID- 19600100
TI  - Report of the Committee on Venereal Diseases.

PMID- 19600102
TI  - Report of the Committee on the Management of Epidemics.

PMID- 19600101
TI  - Minority Report of above Committee.

PMID- 19600103
TI  - Report of the Committee on Vital Statistics.

PMID- 19600105
TI  - Report of the Committee on Necrology.

PMID- 19600104
TI  - Report of the Committee on Compulsory Vaccination.

PMID- 19600106
TI  - Maritime Sanitary Service.

PMID- 19600108
TI  - History of the New Orleans Auxiliary Association.

PMID- 19600107
TI  - The Prevention of Insanity.

PMID- 19600109
TI  - The Municipal Organization of the American Public Health Service.

PMID- 19600110
TI  - The President's Address.

PMID- 19600111
TI  - The Immigrant Inspection Service of the National Board of Health at Port Huron,
      Michigan, and its Bearing on the Public Health of the West and North-West.

PMID- 19600113
TI  - Small-Pox in Bethlehem, Pennsylvania, and Vicinity, in 1881-82.

PMID- 19600112
TI  - A Summer Epidemic of Small-Pox Caused by Direct Importation from Germany.

PMID- 19600114
TI  - Uses and Abuses of Animal Vaccination.

PMID- 19600115
TI  - Propositions concerning Vaccination.

PMID- 19600116
TI  - Observations on Texas Cattle. Age, Weight, Temperature, Liver, and Spleen.

PMID- 19600117
TI  - Stock Transportation.

PMID- 19600118
TI  - Address of Governor A. G. Porter, of Indiana.

PMID- 19600119
TI  - Life on Wheels. Its Sanitary Needs.

PMID- 19600120
TI  - Large Combined Sewers Dangerous to Public Health.

PMID- 19600121
TI  - Address of Mayor D. W. Grubbs, of Indianapolis.

PMID- 19600122
TI  - The Cremation of Excreta and Household Refuse.

PMID- 19600125
TI  - Laws Requiring Medical Men to Report Deaths and Cases of Infectious Diseases to
      the Public Authorities.

PMID- 19600124
TI  - Is Tubercular Consumption a Contagious and Parasitic Disease?

PMID- 19600123
TI  - The Sanitary, Physical, and Educational Advantages of Interior Open-Air Areas in
      Large Cities.

PMID- 19600126
TI  - The Negro Mortality of Memphis.

PMID- 19600127
TI  - Sanitary Government-Principles and Facts.

PMID- 19600128
TI  - Report of Committee on National Museum of Hygiene.

PMID- 19600129
TI  - Report of Committee on Venereal Disease.

PMID- 19600131
TI  - Report of Committee on Management of Epidemics.

PMID- 19600130
TI  - Minority Report of above Committee.

PMID- 19600133
TI  - Sanitary Inspection.

PMID- 19600132
TI  - Report of Committee on Vital Statistics.

PMID- 19600134
TI  - Report of Committee on Compulsory Vaccination.

PMID- 19600135
TI  - Report of Committee on Necrology.

PMID- 19600137
TI  - The Newport (Edinburgh) System of Sanitary Protection.

PMID- 19600136
TI  - The Relations of Health Associations to the Practice of Medicine.

PMID- 19600138
TI  - A History of Health-Work in Indiana.

PMID- 19600139
TI  - Work of the State Board of Health of New York.

PMID- 19600140
TI  - A Review of the Operations of the National Board of Health.

PMID- 19600141
TI  - President's Address-Hygiene: Its Scope, its Progress, and its Leading Aims.

PMID- 19600142
TI  - "Swell-Head" in Cattle.

PMID- 19600143
TI  - Physical Training.

PMID- 19600144
TI  - Physical Training.

PMID- 19600145
TI  - School Hygiene.

PMID- 19600146
TI  - The Sanitary Control of the Food Supply.

PMID- 19600147
TI  - The Adulteration of Foods.

PMID- 19600149
TI  - Vital Statistics as Sanitary Monitors.

PMID- 19600148
TI  - The Eminent Domain of Sanitary Science, and the Usefulness of State Boards of
      Health in Guarding the Public Welfare.

PMID- 19600150
TI  - Essential Features of House Drainage, and Practical Points regarding its Design
      and Construction.

PMID- 19600151
TI  - House Sanitation.

PMID- 19600152
TI  - Preventable Contagious Diseases.

PMID- 19600154
TI  - The Overhead Ventilation of Sewers.

PMID- 19600155
TI  - Report of the Committee on Compulsory Vaccination; also, a Supplementary Report
      on the Efficiency and Safety of Vaccination.

PMID- 19600153
TI  - Address.

PMID- 19600156
TI  - Address.

PMID- 19600157
TI  - Address.

PMID- 19600158
TI  - Pullman from a State Medicine Point of View.

PMID- 19600159
TI  - Typhus Fever in New York City.

PMID- 19600160
TI  - The Pensacola Yellow Fever Epidemic of 1882.

PMID- 19600162
TI  - The Increase of Insanity in the United States: Its Causes and its Sources.

PMID- 19600161
TI  - Malaria.

PMID- 19600164
TI  - Address.

PMID- 19600163
TI  - Swine Plague, or Hog Cholera.

PMID- 19600166
TI  - Reports of the Committee on Publication.

PMID- 19600165
TI  - Report of the Committee on Cattle Diseases.

PMID- 19600167
TI  - Report of the Committee on Management of Epidemics.

PMID- 19600169
TI  - Report of the Committee on the Museum of Hygiene.

PMID- 19600168
TI  - Report on Vital Statistics.

PMID- 19600170
TI  - The Etiological Association of Organic Matter with Malaria.

PMID- 19600171
TI  - On the Prevention of Malarial Diseases.

PMID- 19600172
TI  - The Changes of Type which Malarial Fevers have Undergone in Sumter County,
      Alabama, from 1833 to 1883.

PMID- 19600173
TI  - The Clinical Thermometer in the Prevention of Malarial (Paludal) Fever,
      especially that Form of it to which Seamen Sailing out of South Atlantic and Gulf
      Ports are Liable.

PMID- 19600174
TI  - Interrogatories on Malarial Fever.

PMID- 19600175
TI  - Texas Cattle Fever: Is it a Chimera, or a Reality?

PMID- 19600176
TI  - Observations on Texas Cattle: Age, Weight, Temperature, Liver, and Spleen.

PMID- 19600177
TI  - President's Address-The Sanitary Responsibilities of the Citizen.

PMID- 19600179
TI  - Adulteration of Beer.

PMID- 19600178
TI  - Glucose in its Sanitary Aspects.

PMID- 19600180
TI  - The Ultimate of Sanitation by Fire.

PMID- 19600181
TI  - Cremation as a Safeguard against Epidemics.

PMID- 19600182
TI  - The Squalid Dwellings of the Poor-A Social and Sanitary Reproach.

PMID- 19600184
TI  - The Sanitary Survey of a House.

PMID- 19600183
TI  - Hygiene of the Habitations of the Poor.

PMID- 19600185
TI  - The Hygiene of Occupations.

PMID- 19600187
TI  - The Disposal of Sewage.

PMID- 19600186
TI  - Address.

PMID- 19600188
TI  - The Relation between Underground Sewerage and Filth Diseases.

PMID- 19600189
TI  - The Relation of the Depth of Water in Wells to the Causation of Typhoid Fever.

PMID- 19600190
TI  - Sanitation of the Mississippi Valley.

PMID- 19600192
TI  - The Food We Eat, the Liquids We Drink, and the Adulterations We Submit to.

PMID- 19600191
TI  - Address of Welcome.

PMID- 19600193
TI  - Address.

PMID- 19600194
TI  - Adulterations of Food and Drugs.

PMID- 19600195
TI  - The Use of Cotton-Seed Oil as Food, and for Medicinal Purposes.

PMID- 19600197
TI  - The Milk-Supply of Our Large Cities: The Extent of Adulteration and its
      Consequences: Methods of Prevention.

PMID- 19600196
TI  - Poisonous or "Sick" Cheese.

PMID- 19600199
TI  - On Heating and Ventilation of Dwellings and School-Rooms.

PMID- 19600200
TI  - On Protective Spectacles for Working-Men.

PMID- 19600198
TI  - Address.

PMID- 19600202
TI  - Public Health and Legislation.

PMID- 19600201
TI  - The Chemical Disposition of Sewage.

PMID- 19600203
TI  - On Physical Training in the United States.

PMID- 19600204
TI  - Hardships of the Coasting Trade, and Particularly of the Chesapeake Bay
      Oystermen.

PMID- 19600205
TI  - Sanitary Care in Stock Transportation, in the Prevention and Control of Texas
      Cattle Fever.

PMID- 19600206
TI  - On the Duration of Infectiousness in Scarlet Fever.

PMID- 19600207
TI  - Protection against Hydrophobia.

PMID- 19600208
TI  - The Situation, Surroundings, and Soil of St. Louis, considered from a Hygienic
      Stand-Point.

PMID- 19600210
TI  - Organization of Health Department, Sanitary Legislation, and the Abatement of
      Nuisances.

PMID- 19600209
TI  - The Mean Temperature and Climatic Conditions of St. Louis.

PMID- 19600211
TI  - Sewerage and House Drainage in St. Louis.

PMID- 19600213
TI  - Street and Alley Paving in St. Louis.

PMID- 19600212
TI  - The Public Water-Supply of St. Louis.

PMID- 19600215
TI  - The Leading Local Productive Industries, and their Effect on the Health and Lives
      of their Operatives.

PMID- 19600214
TI  - The Local Milk-Supply-Its Sources and Quality.

PMID- 19600216
TI  - The Chief Local Factors in the Causation of Disease and Death.

PMID- 19600217
TI  - The Manufacture of Soda-Water from Polluted Well-Water.

PMID- 19600218
TI  - The Sanitary Management of Railway Cars and Stations.

PMID- 19600219
TI  - Notes upon the History of Cholera in St. Louis.

PMID- 19600220
TI  - School Hygiene.

PMID- 19600221
TI  - Address from the Provincial Board of Health to the American Public Health
      Association.

PMID- 19600222
TI  - Report of Committee on the Management of Epidemics.

PMID- 19600223
TI  - Report of Committee on "Cattle Diseases".

PMID- 19600224
TI  - Report of Committee on School Hygiene.

PMID- 19600226
TI  - Report of Sub-Committee on Incorporation.

PMID- 19600225
TI  - Report of Committee on Compulsory Vaccination.

PMID- 19600227
TI  - In Memory of Dr. Elisha Harris.

PMID- 19600228
TI  - Deterioration of Vision in School Children.

PMID- 19600229
TI  - Report of Committee on Necrology.

PMID- 19600231
TI  - Disease Germs.

PMID- 19600230
TI  - Sanitary Survey of the School-Houses in Indiana.

PMID- 19600233
TI  - Pollution of the Upper Ohio, and the Water-Supply of the Cities and Chief Towns
      within the First Hundred Miles of its Course.

PMID- 19600232
TI  - On the Present and Future of Sanitary Water Analysis.

PMID- 19600234
TI  - The True Value of Chemical Analysis in Determining the Hygienic Purity of Potable
      Water.

PMID- 19600236
TI  - Experiments in Disinfecting Sewers.

PMID- 19600235
TI  - The President's Address.

PMID- 19600237
TI  - Observations upon the Cape Fear River as a Source of Water-Supply.

PMID- 19600238
TI  - Random Notes for Promoting the Hygiene of the Dwelling.

PMID- 19600239
TI  - Coast Defences against Asiatic Cholera: Report of an Inspection of the
      Quarantines Maintained upon the Atlantic and Gulf Coasts from the St. Lawrence to
      the Rio Grande.

PMID- 19600240
TI  - Notes on the Relations of Rain-fall and Water-Supply to Cholera.

PMID- 19600241
TI  - Small-Pox in Canada, and the Methods of Dealing with it in the Different
      Provinces.

PMID- 19600242
TI  - Physical Training in Germany.

PMID- 19600244
TI  - Report of the Committee on Disinfectants: Part II.

PMID- 19600243
TI  - Report of the Committee on Disinfectants: Part I.

PMID- 19600245
TI  - Address of Welcome.

PMID- 19600246
TI  - Address of Welcome.

PMID- 19600247
TI  - The Debit and Credit Account of the Plymouth Epidemic.

PMID- 19600248
TI  - Letter from President Cleveland.

PMID- 19600249
TI  - Sanitary Nomenclature.

PMID- 19600251
TI  - Report of the Committee on State Boards of Health.

PMID- 19600250
TI  - An Epidemic of Typhoid Fever.

PMID- 19600252
TI  - Report of the Committee on Incorporation.

PMID- 19600253
TI  - Report of the Committee on Necrology.

PMID- 19600255
TI  - Statistics of Consumption in Rhode Island.

PMID- 19600254
TI  - Report of the Committee on School Hygiene.

PMID- 19600256
TI  - Methods of Tabulating and Publishing Records of Death.

PMID- 19600257
TI  - Impure Air and Unhealthy Occupations as Predisposing Causes of Pulmonary
      Consumption.

PMID- 19600258
TI  - The Virus of Hog Cholera.

PMID- 19600259
TI  - The Proper Disposal of the Dead.

PMID- 19600260
TI  - The Sanitary Protection of New Orleans, Municipal and Maritime.

PMID- 19600262
TI  - The President's Address.

PMID- 19600261
TI  - Maritime Sanitation.

PMID- 19600263
TI  - Six Years' Sanitary Work in Memphis.

PMID- 19600265
TI  - Our Inland Lakes and Rivers, the Disposal of Sewage, and the Spread of Infectious
      Diseases.

PMID- 19600264
TI  - Destruction of Night Soil and Garbage by Fire.

PMID- 19600266
TI  - Decomposition of Albuminoid Substances, and some Sanitary Problems connected
      therewith.

PMID- 19600267
TI  - Sanitation in Street Paving.

PMID- 19600268
TI  - Food in its Relation to the Distribution of Wealth.

PMID- 19600269
TI  - The Influence of Sewerage on Health.

PMID- 19600270
TI  - An Experimental Study in Relation to the Removal from the Air of the Dust or
      Particulate Material supposed to produce Yellow Fever, Small-Pox, and other
      Infectious Diseases.

PMID- 19600271
TI  - Report of the Committee on Disinfection of Rags.

PMID- 19600272
TI  - Report of Committee on Disinfectants for 1886.

PMID- 19600273
TI  - Address of Welcome.

PMID- 19600274
TI  - Address.

PMID- 19600275
TI  - Address.

PMID- 19600276
TI  - Report of the Advisory Council.

PMID- 19600277
TI  - Report of Committee on State Boards of Health.

PMID- 19600278
TI  - Reports of the Committees of Award on the Lomb Prize Essays.

PMID- 19600279
TI  - Report of Committee on Disposal of the Dead.

PMID- 19600280
TI  - Address.

PMID- 19600281
TI  - Report of Committee on Animal Diseases and Animal Food.

PMID- 19600282
TI  - Report of Committee on Necrology.

PMID- 19600283
TI  - Recent Progress in Investigation of Hog Cholera.

PMID- 19600284
TI  - Toronto Sewers.

PMID- 19600285
TI  - Medical Science on the Abuse of Alcoholics by the Healthy.

PMID- 19600286
TI  - The Relations Between Sanitary Science and the Medical Profession.

PMID- 19600288
TI  - The President's Address.

PMID- 19600287
TI  - The Best Methods and Apparatus Necessary for the Teaching of Hygiene in the
      Public Schools, as well as the Means for Securing Uniformity in such Instruction.

PMID- 19600289
TI  - Report of Committee on Disinfectants, 1887: Part II.

PMID- 19600290
TI  - Report of Committee on Disinfectants, 1887: Part III.

PMID- 19600291
TI  - On some Forms of Tables of Vital Statistics, with Special Reference to the Needs
      of the Health Department of a City.

PMID- 19600292
TI  - Address.

PMID- 19600293
TI  - The Malarial Germ of Laveran.

PMID- 19600295
TI  - Cholera and Quarantine.

PMID- 19600294
TI  - The Destruction of Garbage.

PMID- 19600297
TI  - Report of Committee on Pollution of Water-Supply.

PMID- 19600296
TI  - Address.

PMID- 19600298
TI  - Water Pollution in Massachusetts.

PMID- 19600300
TI  - Notes on the Pollution of Streams.

PMID- 19600299
TI  - River Pollution in Connecticut.

PMID- 19600302
TI  - Prime Requisites and Suggested Improvements in the Construction and Method of
      Laying Sewers and Drains for House Drainage.

PMID- 19600301
TI  - The Prevention of Microphytic Diseases by Individual Prophylaxis.

PMID- 19600303
TI  - The Necessity of Inspection of Animals required for Food.

PMID- 19600304
TI  - The Meat Food-Supply of the Nation, and its Future.

PMID- 19600305
TI  - Report of the Committee on Necrology.

PMID- 19600306
TI  - The Necessity of Burial Permits and Inspection of the Bodies of Deceased Persons.

PMID- 19600307
TI  - The Origin of some Diseases.

PMID- 19600308
TI  - Sanitary Work by the Health Department of Brooklyn, N. Y.

PMID- 19600309
TI  - Report of Committee on Disinfectants, 1887: Part I.

PMID- 19600310
TI  - The President's Address.

PMID- 19600312
TI  - The Canadian System of Maritime Sanitation.

PMID- 19600311
TI  - The Louisiana Quarantine System and its Contemplated Improvement.

PMID- 19600314
TI  - The Boston Quarantine.

PMID- 19600313
TI  - History of Quarantine in the State of Texas from 1878 to 1888.

PMID- 19600315
TI  - Yellow-Fever Panics and Useless Quarantines-Limitation by Temperature and
      Altitude.

PMID- 19600316
TI  - Garbage Furnaces and the Destruction of Organic Matter by Fire.

PMID- 19600317
TI  - Some Observations on the Origin and Sources of Pathogenic Bacteria.

PMID- 19600318
TI  - Meteorological Observations as respects Disease Prevalence.

PMID- 19600319
TI  - "New Orleans to be Saved must be Drained and Cleaned".

PMID- 19600320
TI  - The Flushing Tunnel at Milwaukee.

PMID- 19600321
TI  - On Pullman, Illinois.

PMID- 19600322
TI  - Report of Committee on Resolutions in Relation to Commissioner of Health.

PMID- 19600323
TI  - Report of Committee on State Boards of Health.

PMID- 19600324
TI  - Report of the Committee to Consider and Report upon such Sanitary and Medical
      Services on Board Emigrant Passenger Vessels as may be subject to Congress.

PMID- 19600325
TI  - Report of the Special Committee on the Transportation of Dead Bodies.

PMID- 19600326
TI  - Report of Committee on the Lomb Prizes.

PMID- 19600327
TI  - Report of the Advisory Council.

PMID- 19600328
TI  - Report of the Committee on Necrology.

PMID- 19600330
TI  - Remarks on the Classification of Disease.

PMID- 19600329
TI  - Address of Welcome.

PMID- 19600331
TI  - Sanitation in St. Paul.

PMID- 19600332
TI  - Proposed Plan for the Disposition of Night-Soil, Garbage, etc., at St. Paul,
      Minn.

PMID- 19600333
TI  - Problems in Regard to Yellow-Fever and the Prevention of Yellow-Fever Epidemics.

PMID- 19600335
TI  - Some Observations on Yellow-Fever and its Habitudes, as opposed to the Fallacies
      and Dangers of Personal Quarantine.

PMID- 19600334
TI  - The Outbreak of Yellow-Fever at Jackson, Miss., in September, 1888.

PMID- 19600336
TI  - Report of Committee on Pollution of Water-Supplies.

PMID- 19600337
TI  - Report of Special Committee to Examine the Southside Water-Supply.

PMID- 19600338
TI  - The Origin and Prevention of Tuberculosis.

PMID- 19600339
TI  - Memoranda of Visits to the Quarantine Stations of the Middle Atlantic Coast, made
      during the Summer of 1888.

PMID- 19600340
TI  - The President's Address.

PMID- 19600341
TI  - The Oleomargarine Law in the United States.

PMID- 19600343
TI  - Certain Provisions of Continental Legislation Concerning Food Adulterations.

PMID- 19600342
TI  - American Methods of Manufacturing Oleomargarine.

PMID- 19600344
TI  - On the Prevention and Restriction of Tuberculosis in Man.

PMID- 19600345
TI  - Notes on the Prevention of Pulmonary Consumption.

PMID- 19600346
TI  - The Prevention of Phthisis Pulmonalis, and Methods for Its Limitation.

PMID- 19600347
TI  - Water-Supply for Drinking Purposes and Water-Closets on Railroads.

PMID- 19600348
TI  - The Art of Cooking.

PMID- 19600349
TI  - Recent Researches Relating to the Etiology of Yellow-Fever.

PMID- 19600351
TI  - Some General Remarks on the Subject of Texas Fever.

PMID- 19600350
TI  - The Necessity for a More Rigorous Inspection of Meat-Producing Animals at the
      Time of Slaughter.

PMID- 19600352
TI  - Preliminary Observations on the Micro-Organism of Texas Fever.

PMID- 19600353
TI  - Sanitary Entombment: The Ideal Disposition of the Dead.

PMID- 19600354
TI  - Address.

PMID- 19600355
TI  - The New York Quarantine Establishment.

PMID- 19600356
TI  - Food and Health.

PMID- 19600357
TI  - Address.

PMID- 19600359
TI  - Address.

PMID- 19600358
TI  - Address.

PMID- 19600360
TI  - Report of Committee on Animal Diseases and Animal Foods.

PMID- 19600361
TI  - Report of the Advisory Council.

PMID- 19600362
TI  - Report of the Committee on Necrology.

PMID- 19600363
TI  - Address.

PMID- 19600364
TI  - The Overshading of Our Homes.

PMID- 19600365
TI  - The United States Census in Its Relations to Sanitation.

PMID- 19600366
TI  - Do the Sanitary Interests of the United States Demand the Annexation of Cuba?

PMID- 19600368
TI  - Statistics of River Pollution, with Observations upon the Destruction of Garbage
      and Refuse Matter.

PMID- 19600367
TI  - A Suggested Minimum Basis of Compensation to Local Heath Officers.

PMID- 19600369
TI  - Disposal of Garbage at Milwaukee.

PMID- 19600371
TI  - The Dwellings of the Laboring Classes in Their Relation to Infant Mortality.

PMID- 19600370
TI  - Disinfection of Dwellings by Means of Sulphur Dioxide.

PMID- 19600372
TI  - Causes and Prevention of Infant Mortality.

PMID- 19600374
TI  - Clothing in Its Relation to Hygiene.

PMID- 19600373
TI  - The Causes of Infant Mortality.

PMID- 19600375
TI  - The President's Address.

PMID- 19600376
TI  - Maritime Sanitation at Ports of Arrival.

PMID- 19600377
TI  - Some Notes on Chemical Disinfection.

PMID- 19600378
TI  - Treatment of Sewage by Chlorine, Precipitation, and Sedimentation.

PMID- 19600379
TI  - Railroad Hygiene: Railroad Cars-Proper Ventilation as a Sanitary Measure to
      Prevent the Transmission of Disease and to Promote the Comfort of Travellers.

PMID- 19600380
TI  - Report of the Committee on Animal Diseases and Animal Foods.

PMID- 19600381
TI  - The Relation of Land Monopoly to Population Health.

PMID- 19600382
TI  - The Federal District in the Republic of Mexico as a Suitable Residence for
      Persons Predisposed to Tuberculous Affections, and for Relief of Pulmonary
      Consumption.

PMID- 19600383
TI  - Swine Red-Disease in Mexico.

PMID- 19600384
TI  - Leprosy and its Management in Minnesota.

PMID- 19600385
TI  - Report from the South Carolina State Board of Health.

PMID- 19600386
TI  - Address of Welcome.

PMID- 19600387
TI  - Local Boards of Health.

PMID- 19600388
TI  - The Hygienic Value of Rational Irregularities in Habits of Living.

PMID- 19600389
TI  - Address.

PMID- 19600390
TI  - Records of Fifty Examples of Defective Plumbing in New York City and Vicinity.

PMID- 19600391
TI  - Sulphuring or Bleaching Dried Fruit a Mistake, if not a Crime.

PMID- 19600392
TI  - The Sanitary Advantages of the Turkish Bath to the Individual.

PMID- 19600394
TI  - The Relation of the Mechanical Arts to Preventive Medicine, Particularly
      Illustrated by the Artesian Wells and Tidal Drains of Charleston, S. C.

PMID- 19600395
TI  - Address.

PMID- 19600393
TI  - Underground Waters as Sources of Public Water-Supplies in Ontario.

PMID- 19600397
TI  - The Microscopical, Spectroscopical, and Chemical Analysis of Black Vomit as an
      Aid to Health Officers in the Differential Diagnosis of Yellow-Fever and Malarial
      Fevers.

PMID- 19600396
TI  - Tidal Drain System of Charleston, S. C.

PMID- 19600398
TI  - Experiments on Trap Siphonage.

PMID- 19600399
TI  - Address.

PMID- 19600400
TI  - What Constitutes a Filth Disease?

PMID- 19600401
TI  - Report of the Committee on Necrology.

PMID- 19600402
TI  - Report of the Mexican Delegates.

PMID- 19600403
TI  - Report of Committee on Sanitary and Medical Service on Emigrant Ships.

PMID- 19600404
TI  - The Vaccinal Protection of Passengers from Europe.

PMID- 19600405
TI  - The Sanitary Improvement of Stagnant Lakes by the Sea-Shore, as Exemplified at
      Virginia Beach, Va.

PMID- 19600406
TI  - The Prevention of Tuberculosis-A Century's Experience in Italy under the
      Influence of the Preventive Laws of the Kingdom of Naples, Enacted in 1782.

PMID- 19600407
TI  - Ventilation and Impure Air as Prophylactic or Causative of Disease.

PMID- 19600409
TI  - Report of the Committee on the Cause and Prevention of Diphtheria.

PMID- 19600408
TI  - On the Prevention of Phthisis.

PMID- 19600410
TI  - The President's Address.

PMID- 19600411
TI  - Address.

PMID- 19600412
TI  - The Present Position of the Milk-Supply Problem from the Public Health Stand
      Point, and some Practical Methods for Securing Safe Public Supplies.

PMID- 19600414
TI  - Animal Diseases.

PMID- 19600413
TI  - Rabies-Its Prevention and Treatment.

PMID- 19600415
TI  - Address.

PMID- 19600417
TI  - The Bath-Its Necessity and Adaptations.

PMID- 19600416
TI  - Vaccine and Vaccination:-Observations and Bacteriological Investigations.

PMID- 19600418
TI  - Considerations upon the Endemical Character of Yellow-Fever upon the Coast of the
      Gulf of Mexico.

PMID- 19600419
TI  - Heights and Weights of Children.

PMID- 19600420
TI  - Some Hints on Diphtheria in the Mexican Highlands.

PMID- 19600421
TI  - Address.

PMID- 19600422
TI  - Arsenical Papers and Fabrics.

PMID- 19600424
TI  - Glanders in Man, with the Report of a Case.

PMID- 19600425
TI  - Algunas Consideraciones Sobre los Progresos de la Higiene en la Republica de
      Mexico.

PMID- 19600423
TI  - Arsenic in Paper and Fabrics.

PMID- 19600426
TI  - The Necessity for More Stringent Legislation to Repress Empiricism.

PMID- 19600427
TI  - Report of the Committee on Necrology.

PMID- 19600428
TI  - Report of the Advisory Council.

PMID- 19600429
TI  - Notes on the Hygiene of Rice Culture.

PMID- 19600430
TI  - New Organization of the Supreme Board of Health of the Mexican Republic.

PMID- 19600431
TI  - The Sewer System of Kansas City, Missouri, and General Comparative Sanitation.

PMID- 19600432
TI  - The Relations of the Plumbers and the Physicians.

PMID- 19600433
TI  - The Drainage of Mexico City.

PMID- 19600434
TI  - Report of the Committee on Car Sanitation.

PMID- 19600435
TI  - Water-Supply and Public Health.

PMID- 19600437
TI  - On the Propagation of Diseases among Chinch-Bugs.

PMID- 19600436
TI  - Land Liberation as a Public Health Measure.

PMID- 19600439
TI  - The President's Address.

PMID- 19600438
TI  - Report of the Committee on Disposal of Waste and Garbage.

PMID- 19600440
TI  - Observations on the Hygienic Conditions of the Territory of Tepic and the Pacific
      Coast of Mexico.

PMID- 19600442
TI  - The Collection, Removal, and Disposal of Garbage and Dead Animals at St. Paul,
      Minnesota, U. S. A.

PMID- 19600441
TI  - A Few Words on Tampico and its Marshes.

PMID- 19600443
TI  - Drinking Waters from the City of Chilpancingo and Hygienic Rules for Using Them.

PMID- 19600444
TI  - In Countries under a Federal Regimen, Can and Should the Union Exercise any
      Intervention on Sanitary Matters? In Which Cases, and How Far, Can This
      Intervention Be Exercised?

PMID- 19600445
TI  - To What an Extent is the Mexican Typhus a Communicable Disease?

PMID- 19600446
TI  - Prophylaxis of Hydrophobia in Mexico.

PMID- 19600447
TI  - The Fundamental Conditions of Public Health in Civilization.

PMID- 19600448
TI  - The Extension of the Use of Live Steam to Municipal and Household Disinfection.

PMID- 19600450
TI  - The Memphis System of Sewerage at Memphis and Elsewhere.

PMID- 19600451
TI  - Project for Strainers for Rain Water in the Streets.

PMID- 19600449
TI  - Address.

PMID- 19600452
TI  - A Personal Experience with Scarlet-Fever, Diphtheria, and Measles in Hospital
      Practice.

PMID- 19600453
TI  - Prevention of Ophthalmia Neonatorum.

PMID- 19600455
TI  - Typhus.

PMID- 19600454
TI  - Epidemic and Endemic Diseases Observed in the Ports of Entry of the Mexican Gulf.

PMID- 19600456
TI  - Observations on the Importance of the American Association of Public Health, and
      its Relations to the Science of Hygiene.

PMID- 19600458
TI  - Phthisis in Guadalajara, Mexico.

PMID- 19600457
TI  - Memoranda Respecting the Palustric Infection in Monterey.

PMID- 19600459
TI  - The City of Tuxpan.

PMID- 19600460
TI  - A Few General Remarks Regarding Yellow-Fever in the State of Tabasco.

PMID- 19600461
TI  - A Case of Yellow-Fever, Observed in the City of Puebla, during the Month of
      November, 1892.

PMID- 19600462
TI  - Streets and Squares in Towns.

PMID- 19600463
TI  - Immunity of the Capital of the State of Mexico from Palustral Complaints.

PMID- 19600464
TI  - Defence of the Ports and Frontier Cities of Mexico against the Epidemic of
      Cholera that Invaded Europe and was on the Point of Invading the United States in
      1892.

PMID- 19600465
TI  - Address of Welcome.

PMID- 19600466
TI  - The Disposal of Garbage in the City of Providence, Rhode Island.

PMID- 19600468
TI  - The Ground of Safety.

PMID- 19600467
TI  - Some Considerations on Parasitism in Yellow-Fever.

PMID- 19600470
TI  - Yellow-Fever in Veracruz.

PMID- 19600469
TI  - Protective Inoculations in Infectious Diseases.

PMID- 19600471
TI  - The Relation of Recent Bacteriological Studies to the Etiology of Typhoid Fever.

PMID- 19600472
TI  - Malarious Localities-How they may be Rendered Salubrious.

PMID- 19600473
TI  - The Quarantine of the Future.

PMID- 19600474
TI  - Contagious Diseases on the Rio Grande Border.

PMID- 19600475
TI  - A Modification of Inner Quarantine Regulations, as Especially Applied to
      Epidemics of Yellow-Fever.

PMID- 19600476
TI  - The Sanitary Relations of Texas and Mexico, and the Official Correspondence
      Relating Thereto.

PMID- 19600477
TI  - Medical Demography.

PMID- 19600478
TI  - Measures Taken by the United States Marine Hospital Service to Prevent the
      Introduction of Cholera.

PMID- 19600479
TI  - Quarantine and the United States Marine Hospital Service.

PMID- 19600480
TI  - Germicidal Value of Steam Heat in Maritime Sanitation.

PMID- 19600481
TI  - Climate of the City of Mexico.

PMID- 19600482
TI  - The Relations of the Official Weather Service to Sanitary Science.

PMID- 19600483
TI  - Note on Herpes-Tonsurans.

PMID- 19600484
TI  - Statistics of Mortality in the City of Mexico.

PMID- 19600485
TI  - The Infectious Diseases Most Frequent in Saltillo and their Hygienic Prophylaxis.

PMID- 19600486
TI  - Sanitary Treatment of Garbage and Infected Materials by the "Simonin Process.".

PMID- 19600487
TI  - Report of Standing Committee on National Health Legislation.

PMID- 19600488
TI  - Report of the Committee on the Disposal of Waste and Garbage.

PMID- 19600489
TI  - Report of Committee on Service on Emigrant Ships.

PMID- 19600490
TI  - Influence of Climate on the Progress and Severity of Pulmonary Tuberculosis in
      the United States of Mexico.

PMID- 19600491
TI  - General Considerations on the Importance of Public Hygiene.

PMID- 19600493
TI  - Zacatecas as a Sanitary Station for Phthisical Patients.

PMID- 19600492
TI  - Contributions to the Bacteriological Study of the Drinking Waters of the City of
      Mexico.

PMID- 19600494
TI  - Notes on Croup in the City of Mexico, and Prophylactic Measures against its
      Growth.

PMID- 19600495
TI  - Etiology and Prophylaxis of Exanthematic Typhus.

PMID- 19600497
TI  - The Mechanical Filtration of Water as a Method of Purification. Based on the
      Investigations Being Made at the Museum of Hygiene, Washington, D. C.

PMID- 19600496
TI  - Notes on the Communication of Disease in Public Places.

PMID- 19600498
TI  - The President's Address.

PMID- 19600499
TI  - Difficulties and Dangers that have Presented Themselves in the Quarantines of
      Several Ports of the Mexican Republic.

PMID- 19600500
TI  - Quarantine.

PMID- 19600501
TI  - The Quarantine System of Texas.

PMID- 19600502
TI  - Conservation of Nerve Forces.

PMID- 19600503
TI  - Report of the International Committee on Yellow-Fever.

PMID- 19600504
TI  - Contribution to the Study of Yellow-Fever from a Medico-Geographical and
      Prophylactic Point of View in the Mexican Republic.

PMID- 19600505
TI  - Vice-President's Address.

PMID- 19600506
TI  - Explanation of the Scientific Principles, and the Data Acquired through
      Experience, on which the Ordinances of the International Maritime Police were
      Founded.

PMID- 19600507
TI  - Report of the Committee "on Sanitary and Medical Service on Board Emigrant
      Ships.".

PMID- 19600508
TI  - The Water-Supply of Chicago: Its Source and Sanitary Aspects.

PMID- 19600509
TI  - Address of Welcome.

PMID- 19600510
TI  - On the Removal of Pathogenic Bacteria from Drinking Water by Sand Filtration.

PMID- 19600511
TI  - Prophylactic and Therapeutic Value of Food.

PMID- 19600513
TI  - The Progress of Sanitary Knowledge among the Women of England.

PMID- 19600512
TI  - Municipal Hygiene and Sanitation.

PMID- 19600514
TI  - Voluntary Public Health and Sanitary Organizations.

PMID- 19600516
TI  - Remarks.

PMID- 19600515
TI  - How Can Women Best Promote Public Sanitation?

PMID- 19600518
TI  - Importance of Civil Public Hygiene to the State.

PMID- 19600517
TI  - Brief Notice of the Climate and Diseases of Brazil, Especially of the City of Rio
      de Janeiro.

PMID- 19600519
TI  - Remarks.

PMID- 19600521
TI  - Tuberculosis and the Food Supply.

PMID- 19600520
TI  - Report of the Committee on the Pollution of Water-Supplies.

PMID- 19600522
TI  - Remarks.

PMID- 19600523
TI  - Some Considerations About the Influence of Habitation in the Development of
      Tuberculosis.

PMID- 19600524
TI  - Can Syphilitic Contagion Form the Vehicle for the Transmission of Tuberculosis as
      Well?

PMID- 19600525
TI  - Report of the Committee on Restriction and Prevention of Tuberculosis.

PMID- 19600526
TI  - An Experiment in Disinfection-How an Epidemic of Pneumonia was Checked.

PMID- 19600527
TI  - Overwork and Unrest.

PMID- 19600529
TI  - Los Ejercicios Fisicos: La Higiene.

PMID- 19600528
TI  - Apuntes Sobre la Escarlatina en la Ciudad de Puebla, Mexico.

PMID- 19600530
TI  - Los Carros Dormitorios no Lleman las Condiciones que la Higiene Exige.

PMID- 19600531
TI  - La Gripa, sus Formas y Complicaciones en Orizaba-su Profilaxia.

PMID- 19600532
TI  - Las Aguas Potables de los Campos Presentan Muchos Peligros.

PMID- 19600533
TI  - The Origin and Dissemination of Typhoid Fever.

PMID- 19600534
TI  - Municipal Sanitation.

PMID- 19600535
TI  - How Shall our Lepers be Cared For?

PMID- 19600536
TI  - Notes on Cholera, and its Management in Hull.

PMID- 19600537
TI  - El Tifo de Enero de 1889 a Junio de 1893 en el Hospital Juarez.

PMID- 19600538
TI  - Algunas Reflexiones Acerca de la Infeccion y el Contagio del Tifo Exantematico.

PMID- 19600539
TI  - Report on Necrology.

PMID- 19600540
TI  - Tropical Diarrhoea.

PMID- 19600541
TI  - Cholera Infantum: Its Treatment.

PMID- 19600542
TI  - The Sewage Disposal Problem in American Cities.

PMID- 19600543
TI  - The Collection and Disposal of Animal and Vegetable Waste in the City of
      Milwaukee.

PMID- 19600544
TI  - The Disposal of the Garbage and Waste of the World's Columbian Exposition.

PMID- 19600545
TI  - National Registration a Necessity.

PMID- 19600546
TI  - Importance of Sanitary Bureaus; Their Economic Organism.

PMID- 19600547
TI  - Objects of the National Health Society of London.

PMID- 19600549
TI  - Hygiene of Hair-Dressers' and Barbers' Shops.

PMID- 19600548
TI  - Influence of Inebriety on Public Health.

PMID- 19600550
TI  - Animal Vaccine-Why it Should be Preferred to Human Vaccine.

PMID- 19600552
TI  - The Canadian Quarantine System.

PMID- 19600551
TI  - Yellow Coloration of Persons Attacked by "Vomito Prieto.".

PMID- 19600553
TI  - Introduction.

PMID- 19600555
TI  - Discussion on the Three Preceding Papers.

PMID- 19600554
TI  - Des Inoculations Preventives Dans Les Maladies Contagieuses.

PMID- 19600556
TI  - Innocuous Transportation of the Dead.

PMID- 19600557
TI  - The Restriction and Prevention of Tuberculosis.

PMID- 19600559
TI  - Should the Marriage of Consumptives be Discouraged?

PMID- 19600558
TI  - Tuberculosis: Its Restriction and Prevention.

PMID- 19600560
TI  - The Climatic Segregation of Consumptives.

PMID- 19600561
TI  - Examination of the Milk-Supply for Tuberculosis in the State of New York.

PMID- 19600562
TI  - Address.

PMID- 19600563
TI  - Discussion of Papers on Tuberculosis.

PMID- 19600564
TI  - Vaccine and Vaccination.

PMID- 19600565
TI  - On the Culture and Collection of Vaccine Virus.

PMID- 19600566
TI  - A Plea for Aseptic Vaccination.

PMID- 19600567
TI  - The Domestic Disposal of Garbage.

PMID- 19600569
TI  - Remarks on Disposal of Garbage and Household Refuse.

PMID- 19600568
TI  - Address.

PMID- 19600570
TI  - The Collection and Disposal of the Refuse of Large Cities.

PMID- 19600571
TI  - Report of the Committee on the Disposal of Garbage and Refuse.

PMID- 19600572
TI  - Prevention of the Spread of Yellow Fever.

PMID- 19600573
TI  - Address.

PMID- 19600574
TI  - Report of the International Committee on the Prevention of the Spread of Yellow
      Fever.

PMID- 19600575
TI  - Address.

PMID- 19600576
TI  - Contribution to the Study of Yellow Fever.

PMID- 19600577
TI  - Car Sanitation.

PMID- 19600578
TI  - Report of the Committee on Car Sanitation.

PMID- 19600579
TI  - Instruction in Hygiene in Schools and Colleges.

PMID- 19600580
TI  - The Hygiene of Vision in Schools.

PMID- 19600581
TI  - Teaching of Hygiene in the Elementary Schools.

PMID- 19600582
TI  - Hygienic Notes Made on a Short Journey Through Italy in 1894.

PMID- 19600583
TI  - On Teaching the Principles of Hygiene to the Young.

PMID- 19600584
TI  - Some Points in the Hygiene of the Young in Schools.

PMID- 19600586
TI  - A Few Remarks on School Hygiene.

PMID- 19600585
TI  - Necesidad de Ensenar la Higiene en las Escuelas de Instruccion Primaria por el
      Metodo Objectivo.

PMID- 19600587
TI  - Discussion on School Hygiene.

PMID- 19600588
TI  - Ventilation of School-Houses.

PMID- 19600589
TI  - Myopia in its Relations with Scholastic Hygiene.

PMID- 19600590
TI  - Discussion on Myopia and Scholastic Hygiene.

PMID- 19600591
TI  - Hygiene in Medical Education.

PMID- 19600593
TI  - Drainage of Montreal.

PMID- 19600592
TI  - The Present State of Sanitation in Montreal.

PMID- 19600594
TI  - Modern Difficulties in Bacteriological Diagnosis.

PMID- 19600596
TI  - Plumbing in Sanitation.

PMID- 19600595
TI  - The Evolutionary Developments of Domestic Plumbing During the Past Thirty-Five
      Years.

PMID- 19600597
TI  - The Condition of the Children's Teeth of the Present Day, and the Effects of
      Decayed Teeth on the Health of the Children.

PMID- 19600598
TI  - The Cart Before the Horse.

PMID- 19600599
TI  - Quarantine Appliances Illustrated.

PMID- 19600601
TI  - Discussion on Influence of Inebriety on Public Health.

PMID- 19600600
TI  - Influence of Inebriety on Public Health.

PMID- 19600603
TI  - Report of the Committee on Water Supplies.

PMID- 19600602
TI  - Infection by the Bacillus Pyocyaneus a Cause of Infantile Mortality.

PMID- 19600604
TI  - Notes Concerning the Nourishment of Children in their Earliest Infancy, Exclusive
      of Nursing at the Breast.

PMID- 19600605
TI  - A Few Observations Upon Sedimentation in Water.

PMID- 19600606
TI  - On the Proper Reaction of Nutrient Media for Bacterial Cultivation.

PMID- 19600607
TI  - What Method Shall Be Adopted by Which Full Benefit May Be Derived From
      Morphological Characteristics?

PMID- 19600608
TI  - Nomenclature of Colors for Bacteriologists.

PMID- 19600610
TI  - The Long Island Water Basin-Brooklyn's Reservoir.

PMID- 19600609
TI  - On the Peculiar Method of Branching in the Genus Cladothrix, and the Value of the
      Same in Systematic Bacteriology.

PMID- 19600611
TI  - What Shall Be the Methods Followed in Determining the Relation of Bacteria to
      Temperature?

PMID- 19600612
TI  - How is Variability in Bacteria to be Regarded?

PMID- 19600614
TI  - On the Nature of the Flagella and Their Value in the Systematic Classification of
      Bacteria.

PMID- 19600613
TI  - Opening Discussion on "What New Methods Can be Suggested for the Separation of
      Bacteria Into Groups and for the Identification of Species?".

PMID- 19600615
TI  - The Well Waters of Our Farm Homesteads.

PMID- 19600616
TI  - On Grouping Water Bacteria.

PMID- 19600617
TI  - On the Influence of Variations in the Composition of Nutrient Gelatin Upon the
      Development of Water Bacteria.

PMID- 19600618
TI  - Pure Water vs. Purified Water for Public Water Supplies.

PMID- 19600619
TI  - The President's Address.

PMID- 19600620
TI  - Report of the Committee on Nomenclature and Forms of Statistics.

PMID- 19600621
TI  - Water Supply for Towns.

PMID- 19600622
TI  - A Provisional Arrangement of Causes of Death.

PMID- 19600623
TI  - Las Cuarentenas Aplicadas a la Viruela.

PMID- 19600624
TI  - Some Deductions from Bacteriological Work on the Water of Lake Ontario.

PMID- 19600625
TI  - Sand Filtration of Water, With Special Reference to Results Obtained, at
      Lawrence, Massachusetts.

PMID- 19600627
TI  - Discussion on the Foregoing Group of Papers From "The Cart Before the Horse" to
      the "Report of the Committee on the Pollution of Water Supplies," Inclusive.

PMID- 19600626
TI  - Report of the Committee on Pollution of Water Supplies.

PMID- 19600628
TI  - Management of Diphtheria Epidemics in Rural Districts.

PMID- 19600629
TI  - Practical Difficulties of Medical Health Officers and Physicians in Dealing With
      Suspected Cases of Diphtheria.

PMID- 19600630
TI  - President's Address.

PMID- 19600632
TI  - Editorial Notes.

PMID- 19600631
TI  - Remarks.

PMID- 19600633
TI  - Report of the Committee on Animal Diseases and Animal Foods.-Necessity for
      Cooperation in the Inspection of Metas.

PMID- 19600634
TI  - The Special Influence of Altitude upon Health, Disease, and Sanitation.

PMID- 19600635
TI  - Suggestions as to Ocular Hygiene in the Schools.

PMID- 19600637
TI  - Bacteriological Results from Mechanical Filtration.

PMID- 19600636
TI  - Medical Inspection of Schools.

PMID- 19600639
TI  - Prophylaxis of Yellow Fever.

PMID- 19600638
TI  - Contribution to the Study of Yellow Fever in Connection with its Medical
      Geography and Prophylaxis in the Mexican Republic.

PMID- 19600640
TI  - Means of Correcting the Abuse of Alcoholic Drinks.

PMID- 19600641
TI  - Report of the Committee on the Disposal of the Dead.

PMID- 19600642
TI  - The Microscopical Diagnosis of Diphtheria by a New Staining Method.

PMID- 19600643
TI  - The Disposal of the Dead, with Especial Reference to the Prevalent Practice of
      Embalming.

PMID- 19600644
TI  - Cremation or Earth Burial, which?

PMID- 19600645
TI  - Disinfection in American Cities.

PMID- 19600647
TI  - Municipal Steam Disinfection.

PMID- 19600646
TI  - The Mississippi River as a Sewer.

PMID- 19600648
TI  - The Outlook for a General System of Registration of Vital Statistics in the
      United States.

PMID- 19600650
TI  - Baths-Their Necessity, their Influence in Economy, the Dangers they Present, and
      the Manner to Prevent them.

PMID- 19600649
TI  - Degenerative Heredity, or Some Degenerative Influences of Modern Civilization
      upon Health.

PMID- 19600652
TI  - Small-Pox in Wisconsin from January, 1894, to June, 1895.

PMID- 19600651
TI  - Necessity and Desirability of Popularizing the Study of Hygiene.

PMID- 19600653
TI  - Some Remarks as to Abortions and Still Births, and their Relation to Hygiene.

PMID- 19600655
TI  - The Part which Pauperism Plays in Cities. Its Extinction is the Best Prophylactic
      Means against Typhus.

PMID- 19600654
TI  - The Necessity of Establishing Sanitariums for Treating Young Ladies Afflicted
      with Chlorosis. They Would be the Best Prophylactic Means against Tuberculosis in
      Particular, and Constitutional Diseases in General.

PMID- 19600656
TI  - Report of the Committee on Car Sanitation.

PMID- 19600658
TI  - The Contagion of Venereal Diseases on Railroads.

PMID- 19600657
TI  - Observations on the Cleaning of Railroad Passenger Cars.

PMID- 19600659
TI  - Report of the Committee on Steamship and Steamboat Sanitation.

PMID- 19600660
TI  - Report of Chairman of Committee on Pollution of Water-Supplies.

PMID- 19600661
TI  - Report of the Committee on River Conservancy Boards of Supervision.

PMID- 19600662
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19600663
TI  - The Composition and Infectiousness of Milk.

PMID- 19600664
TI  - Rivers Conservancy Boards.-From the International Standpoint.

PMID- 19600665
TI  - A Formic Aldehyde: Its Practical Use.

PMID- 19600666
TI  - A Convenient Lamp for the Generation of Formaldehyde Gas, and a Method of
      Determining the Amount of this Gas in a Given Space.

PMID- 19600668
TI  - Upon the Operation of Foreign Methods of Sewage Disposal by Treating it upon
      Land.

PMID- 19600667
TI  - Industrial Hygiene.

PMID- 19600669
TI  - Vaccination.

PMID- 19600670
TI  - Vital Statistics.

PMID- 19600671
TI  - The Softening of Hard Water.

PMID- 19600672
TI  - Notes on the Soil Factor in the Development and Prevention of Infectious
      Diseases.

PMID- 19600673
TI  - Report of the Committee on Car Sanitation.

PMID- 19600674
TI  - Address of Welcome.

PMID- 19600675
TI  - On the Ventilation of Railway Coaches.

PMID- 19600676
TI  - Address.

PMID- 19600677
TI  - Contribution to the Discussion of Railroad Hygiene.

PMID- 19600678
TI  - Report of the Committee "On the Abuse of Alcoholic Drinks from a Sanitary
      Standpoint".

PMID- 19600679
TI  - Measures which Ought to be Adopted for Limiting the Consumption of Impure Alcohol
      as a Beverage.

PMID- 19600680
TI  - The President's Address.

PMID- 19600682
TI  - Report of the Committee on the Disposal of Garbage and Refuse.

PMID- 19600681
TI  - Vital Statistics.

PMID- 19600683
TI  - The Disposal of Garbage and Waste in the Household.

PMID- 19600685
TI  - Report of the Committee on Nomenclature of Diseases and Forms of Statistics.

PMID- 19600684
TI  - Filth Deposits with Regard to Public Health.

PMID- 19600687
TI  - Address of Welcome.

PMID- 19600686
TI  - Necessity of Uniformity in the Meaning of the Term Still-Birth.

PMID- 19600688
TI  - Discussion of the Report on Nomenclature and Forms of Statistics.

PMID- 19600689
TI  - Report of the Committee on the Transportation and Disposal of the Dead.

PMID- 19600690
TI  - Obiter Dicta concerning Sanitary Organization.

PMID- 19600691
TI  - Some Thoughts Relative to Sanitary Legislation.

PMID- 19600692
TI  - Sanitary Administration in Unincorporated Districts.

PMID- 19600693
TI  - An Address.

PMID- 19600694
TI  - Necessity of the Study by Sanitary Congresses of Measures for the Prevention of
      Blindness.

PMID- 19600695
TI  - Report of Committee on Yellow Fever.

PMID- 19600696
TI  - Contribution to the Study of Yellow Fever from a Medico-Geographical Point of
      View.

PMID- 19600697
TI  - Contribution to the Study of Yellow Fever in Relation to Epidemics in Cordova.

PMID- 19600698
TI  - Contribution to the Study of the Pathogeny, Etiology, and Prophylaxis of Typhus.

PMID- 19600699
TI  - The Quick or the Dead.

PMID- 19600700
TI  - Public Bathing Establishments, with a Description of the New Public Bath in
      Brookline, Massachusetts.

PMID- 19600701
TI  - Pertaining to Public Health in Tabasco, Mexico.

PMID- 19600702
TI  - Remarks.

PMID- 19600703
TI  - Dengue.

PMID- 19600704
TI  - Municipal Cattle and Meat Inspection.

PMID- 19600705
TI  - Remarks.

PMID- 19600706
TI  - Isolation Hospitals.

PMID- 19600707
TI  - Prophylaxis of Paludism.

PMID- 19600708
TI  - Paludism in the State of Morelos and its Prophylaxis by Sanitary Measures.

PMID- 19600709
TI  - Discussion on the Papers of Drs. Erdozain and Gavino.

PMID- 19600710
TI  - Sanitation in Hospitals for the Insane.

PMID- 19600711
TI  - The Protection of the Innocent from Gonorrhoea.

PMID- 19600712
TI  - Drunkenness a Vice-It should be so Treated.

PMID- 19600713
TI  - On the Application of the Serum Diagnosis of Typhoid Fever to the Requirements of
      Public Health Laboratories.

PMID- 19600715
TI  - Discussion on the Papers of Drs. Johnston and Woodbridge.

PMID- 19600714
TI  - The Prophylaxis of Typhoid Fever.

PMID- 19600716
TI  - Racial Deterioration: The Relation between Phthisis and Insanity.

PMID- 19600717
TI  - Pulque as a Prophylaxis of Scurvy in Prisons.

PMID- 19600718
TI  - Miasmatic Fevers in the State of Sonora.

PMID- 19600719
TI  - Should Measles be Quarantined?

PMID- 19600720
TI  - Summary of Sanitary Legislation in the State of Mexico.

PMID- 19600721
TI  - Mortality of Children-Its Causes, and Means of Diminishing it.

PMID- 19600723
TI  - Report of the Committee on the Transportation of Diseased Tissues by Mail.

PMID- 19600722
TI  - Ventilation-The Necessity of Isolating the Beds in Hospitals by Means of Windows
      Placed between the Beds.

PMID- 19600724
TI  - Statistics of Vaccination and of Small Pox in the City of Mexico from 1872 to
      1895.

PMID- 19600725
TI  - The Bicycle as a Sanitary Measure.

PMID- 19600726
TI  - Report of the Committee on the Cause and Prevention of Diphtheria.

PMID- 19600727
TI  - Bacteriological Diagnosis as Governing the Admission and Discharge of Patients in
      Diphtheria Hospitals.

PMID- 19600728
TI  - Diphtheria in Chihuahua.

PMID- 19600729
TI  - Discussion on the Papers of Drs. Kinyoun, Marquez, and Shuttleworth.

PMID- 19600731
TI  - Municipal Responsibility for Healthful School-Houses.

PMID- 19600730
TI  - A Plea for the Domestic Disposal of Garbage.

PMID- 19600733
TI  - Anthrax in London.

PMID- 19600734
TI  - Infectious Diseases.

PMID- 19600732
TI  - Importance of Attention to Health.

PMID- 19600737
TI  - Food and Drug Inspection.

PMID- 19600735
TI  - Infectious Disease Hospital Accommodation.

PMID- 19600736
TI  - The Spread of Diphtheria.

PMID- 19600738
TI  - Summary.

PMID- 19600739
TI  - Sewage Farms.

PMID- 19600740
TI  - Milk Standard.

PMID- 19600741
TI  - The President's Address.

PMID- 19600742
TI  - Report of the Committee on Disinfectants.

PMID- 19600743
TI  - Fumigation with Formaldehyde.

PMID- 19600744
TI  - Some Experiments with Formaldehyde Gas.

PMID- 19600746
TI  - Disinfection by the Fumes from Burning Coffee; an Experimental Study.

PMID- 19600745
TI  - The Amount of Formaldehyde Gas Yielded by Different Lamps and Generators.

PMID- 19600748
TI  - The Serum Diagnosis of Typhoid Fever from the Public Health Laboratory Point of
      View.

PMID- 19600747
TI  - Discussion of the Report and Papers on Disinfection.

PMID- 19600749
TI  - A Statistical Summary of Results Obtained in the Laboratory of the Board of
      Health of Philadelphia in the Diagnosis of Typhoid Fever by Widal's Blood
      Reaction.

PMID- 19600750
TI  - Discussion on Diagnosis of Typhoid Fever.

PMID- 19600751
TI  - How to Prevent Typhoid Fever in Rural Districts.

PMID- 19600752
TI  - Typhoid Infection.

PMID- 19600754
TI  - The Arid Atmosphere of our Homes in Winter.

PMID- 19600753
TI  - The Present Mortality Rate in Diphtheria; upon what its further Reduction by the
      Serum Treatment will Depend.

PMID- 19600755
TI  - Air Moisteners.

PMID- 19600756
TI  - Discussion of paper.

PMID- 19600757
TI  - Investigations of Water Supply by the United States Geological Survey.

PMID- 19600758
TI  - A Brief Review of the Work of the Sand Filters at Lawrence, Mass.

PMID- 19600759
TI  - An Apparatus for the Collection of Samples of Water.

PMID- 19600761
TI  - The Origin of Free and Albuminoid Ammonias in Polluted Waters.

PMID- 19600760
TI  - The City of Mexico after the Drainage of the Valley and the Sanitation Works.

PMID- 19600762
TI  - Report of the Committee on the Disposal of Garbage and Refuse.

PMID- 19600763
TI  - Discussion on Disposal of Garbage and Refuse.

PMID- 19600764
TI  - Report on Laboratory Diagnosis in Twenty Cases of Suspected Rabies.

PMID- 19600766
TI  - Discussion on Steamship and Steamboat Sanitation.

PMID- 19600765
TI  - Report of the Committee on Steamship and Steamboat Sanitation.

PMID- 19600767
TI  - Report of Committee on Car Sanitation.

PMID- 19600769
TI  - Discussion on Car Sanitation.

PMID- 19600768
TI  - Report of the Committee on Car Sanitation.

PMID- 19600771
TI  - Address of Welcome.

PMID- 19600770
TI  - Consumption; an Indoor Disease.

PMID- 19600772
TI  - The Place of the State in Dealing with Tuberculosis.

PMID- 19600773
TI  - Address of Welcome.

PMID- 19600774
TI  - Tuberculosis and Milk Supply.

PMID- 19600775
TI  - The Urgent Need of Sanitation for the Consumptive Poor of our Large Cities.

PMID- 19600776
TI  - Bovine Tuberculosis in its Relation to the Public Health.

PMID- 19600777
TI  - Discussion on the Papers on Tuberculosis.

PMID- 19600778
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19600779
TI  - Methods of Meat Inspection.

PMID- 19600781
TI  - Necessity of Adopting an International Classification for the Professions.

PMID- 19600780
TI  - Report of the Committee on the Nomenclature of Diseases and Forms of Statistics.

PMID- 19600782
TI  - Nomenclature of Professions.

PMID- 19600783
TI  - Discussion on the Paper of Dr. Monjaras.

PMID- 19600784
TI  - Michigan's New System of Registration of Deaths.

PMID- 19600785
TI  - A Uniform Sanitary Law.

PMID- 19600786
TI  - Uniform and Co-operative Health Laws.

PMID- 19600787
TI  - Discussion on Uniform and Co-operative Health Laws.

PMID- 19600789
TI  - Discussion on the Report of the Committee on Public Health Legislation.

PMID- 19600788
TI  - Report of the Committee on Public Legislation.

PMID- 19600791
TI  - House Sanitation, with Reference to Drainage, Plumbing, and Ventilation.

PMID- 19600790
TI  - Report of the Committee on Sanitation with Special Reference to Drainage,
      Plumbing, and Ventilation of Public and Private Buildings.

PMID- 19600792
TI  - Discussion of Papers on Drainage, Plumbing, and Ventilation of Public and Private
      Buildings.

PMID- 19600794
TI  - The Relation between Woman's Health Protective Associations and the Public
      Health.

PMID- 19600793
TI  - Report of the Committee on Transportation of Diseased Tissues by Mail.

PMID- 19600796
TI  - Recent Researches Relating to the Etiology and Specific Treatment of Yellow
      Fever.

PMID- 19600795
TI  - Contribution to the Study of Yellow Fever from a Medico-Geographical Point of
      View.

PMID- 19600797
TI  - The Barber Shop as a Menace to the Public Health.

PMID- 19600798
TI  - Preliminary Report of the Chairman of the Committee Appointed "To Examine into
      the Existing Sanitary Municipal Organizations of the Countries Represented in the
      Association, with a view to Report upon those Most Successful in Practical
      Results.".

PMID- 19600799
TI  - Report of the Committee on the Transportation and Disposal of the Dead.

PMID- 19600800
TI  - How to Practice Isolation from the Contagious Diseases.

PMID- 19600802
TI  - Some Considerations on the Hygienic Influence of Forests.

PMID- 19600801
TI  - The Diagnosis of Small-Pox.

PMID- 19600803
TI  - A New Contribution to the Study of the Etiology of the Typhus Prevailing in the
      Mexican Central Plateau.

PMID- 19600804
TI  - The Disabilities and Mortality of Children under Five Years of Age.

PMID- 19600805
TI  - Eye-Strain from Poor Window-Glass, its Importance and Prevention.

PMID- 19600806
TI  - Report of a Committee of Bacteriologists to the Committee of the American Public
      Health Association on the Pollution of Water Supplies.

PMID- 19600807
TI  - President's Address.

PMID- 19600809
TI  - Theatre Sanitation.

PMID- 19600810
TI  - Report of the Committee on the Etiology of Yellow Fever.

PMID- 19600808
TI  - The Urgent Need of Sanitary Education in the Public Schools.

PMID- 19600811
TI  - Etiology of Yellow Fever.

PMID- 19600812
TI  - Seventh Report on Yellow Fever.

PMID- 19600814
TI  - Report of the Committee on the Cause and Prevention of Infant Morality.

PMID- 19600813
TI  - Address of Welcome.

PMID- 19600815
TI  - Some Observations on Bovine Tuberculosis in New Hampshire.

PMID- 19600817
TI  - Address of Welcome.

PMID- 19600816
TI  - A New Stain for Bacillus Tuberculosis.

PMID- 19600819
TI  - Report of the Committee on Demography and Statistics in their Sanitary Relations.

PMID- 19600818
TI  - Compulsory Vaccination Ought to be Imposed as a Paramount Necessity.

PMID- 19600820
TI  - Ought We to Reopen the Leper Asylums?

PMID- 19600821
TI  - Leprosy in Minnesota.

PMID- 19600822
TI  - Address of Welcome.

PMID- 19600823
TI  - Report of the Committee on Sanitation, with Special Reference to Drainage,
      Plumbing and Ventilation of Public and Private Buildings.

PMID- 19600825
TI  - On the Working of the Food and Drug Adulteration Act in Canada.

PMID- 19600824
TI  - Illuminating Gas More Dangerous to Health than Sewer Gas.

PMID- 19600827
TI  - Report of the Committee on Car Sanitation.

PMID- 19600826
TI  - Rough Notes on the Etiology of Typhus Fever.

PMID- 19600828
TI  - Address of Welcome.

PMID- 19600830
TI  - Some Standard Disinfectants and the Conditions for their Greatest Efficiency.

PMID- 19600829
TI  - Dermatosis as Commonly Transmitted to the Pupils of Public Schools by Contagion,
      and Means of Prevention.

PMID- 19600831
TI  - Address of Welcome.

PMID- 19600832
TI  - A Method of Preparing Test Objects for Disinfection Experiments.

PMID- 19600833
TI  - Methods of Testing Disinfection.

PMID- 19600835
TI  - Disinfectants in Quarantine Work.

PMID- 19600834
TI  - Disinfection in Cities.

PMID- 19600836
TI  - The Diptera from a Hygienic Point of View.

PMID- 19600837
TI  - Response to the Addresses of Welcome.

PMID- 19600838
TI  - The Spread of Typhoid and Dysenteric Diseases by Flies.

PMID- 19600840
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19600839
TI  - Report of the Committee on the Transportation of Diseased Tissues by Mail.

PMID- 19600841
TI  - A Short History of Sewage Disposal at the Asylum for Insane, London, Ontario.

PMID- 19600842
TI  - Report of the Committee on "The Duties and Responsibilities of the Healthy Man
      for his Own and Others Health.".

PMID- 19600843
TI  - Infected Milk Supply.

PMID- 19600845
TI  - The Treatment of Inebriates.

PMID- 19600844
TI  - Preventive Antirabic Inoculation Service in Mexico.

PMID- 19600846
TI  - Garbage Reduction by Steam.

PMID- 19600848
TI  - Anthrax: The Effect of Tanneries in Spreading the Disease.

PMID- 19600847
TI  - Report of the Committee on Public Health Legislation.

PMID- 19600849
TI  - Remarks on the Disposal of Refuse in Some European Cities.

PMID- 19600850
TI  - The Most Recent Methods of Sewage Disposal in the United States, with Remarks
      upon their Adaptability to Cities in Canada.

PMID- 19600851
TI  - The Filtration of Sewage.

PMID- 19600853
TI  - An Outbreak of Typhoid Fever Due to an Infected Public Water Supply.

PMID- 19600852
TI  - The Farm Well.

PMID- 19600854
TI  - Report of the Committee on Cause and Prevention of Contagious Diseases.

PMID- 19600855
TI  - Typhus Fever in San Luis Potosi.

PMID- 19600856
TI  - Diphtheria: Suggestions for its Prevention and Limitation.

PMID- 19600858
TI  - What Constitutes an Epidemic?

PMID- 19600857
TI  - Remarks upon Scarlet Fever.

PMID- 19600859
TI  - President's Address.

PMID- 19600860
TI  - Some Remarks on the Etiologie and Prophylaxis of the Transmissible Diseases.

PMID- 19600861
TI  - Report of Committee on Infant Mortality.

PMID- 19600862
TI  - Formaldehyd as a Milk Preservative.

PMID- 19600863
TI  - Address of Welcome on Behalf of the State.

PMID- 19600864
TI  - Food Adulteration in its Relation to the Public Health.

PMID- 19600865
TI  - The Transmission of Typhoid by Sewage Polluted Oysters.

PMID- 19600866
TI  - An Epidemic of Typhoid Fever Due to an Infected Water Supply.

PMID- 19600868
TI  - Report on Typhoid Fever-Newark, N. J.-1898-99.

PMID- 19600867
TI  - Address of Welcome on Behalf of the City of Minneapolis.

PMID- 19600869
TI  - A Report of a Four Months' Test of a Mechanical Filter Plant at East Providence,
      R. I.

PMID- 19600870
TI  - The Bacterial Purification of Sewage.

PMID- 19600871
TI  - Address of Welcome on Behalf of the Medical Profession.

PMID- 19600873
TI  - Address.

PMID- 19600872
TI  - Report of the Committee to Examine into the Existing Sanitary Municipal
      Organizations.

PMID- 19600874
TI  - Rural Sanitation in England.

PMID- 19600875
TI  - History of Vaccination.

PMID- 19600876
TI  - The Accidents of Vaccination.

PMID- 19600877
TI  - A Cause for Unsuccessful Vaccinations.

PMID- 19600878
TI  - Report of Committee on the Etiology of Yellow Fever.

PMID- 19600879
TI  - Report of Committee to Define what Constitutes an Epidemic.

PMID- 19600880
TI  - The Official Definition of Diphtheria.

PMID- 19600881
TI  - The Nature Treatment of Tuberculosis.

PMID- 19600882
TI  - Instructions to Persons Suffering from Diseases of the Chest, and to Their
      Attendants and for Preventing the Diffusion of Such Diseases.

PMID- 19600883
TI  - Electrozone.

PMID- 19600884
TI  - Sixteen Years' Experience in Food and Drug Inspection.

PMID- 19600885
TI  - Report of a Committee on a National Home for Lepers in the United States.

PMID- 19600886
TI  - The Leper Home of Louisiana.

PMID- 19600887
TI  - The Treatment of Garbage and Excreta in Military Camps.

PMID- 19600888
TI  - Waste Disposal and its Advances.

PMID- 19600889
TI  - The Next Step in the Work of Refuse and Garbage Disposal.

PMID- 19600891
TI  - A Report of Work with Antitoxin and Formaldehyd against Diphtheria.

PMID- 19600890
TI  - Arrangement of the Sanitary Stations which the Board of Health Proposes to
      Establish to Prevent the Propagation of Yellow Fever.

PMID- 19600892
TI  - Report of the Committee on Demography and Statistics in Their Sanitary Relation.

PMID- 19600893
TI  - Report of the Commission of Revision of the Bertillon Classification of Causes of
      Death.

PMID- 19600894
TI  - Methods of Compilation Used in Preparing Census and Registration Reports.

PMID- 19600895
TI  - Representative Mortality Statistics.

PMID- 19600897
TI  - Contribution to the Study of the Contagiousness of Paludism and Prophylaxia of
      the Same.

PMID- 19600896
TI  - Eighth Report Presented to the Committee on the Etiology of Yellow Fever.

PMID- 19600899
TI  - Report of the Committee on Car Sanitation.

PMID- 19600898
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19600900
TI  - Dangers to the Public Health from Illuminating and Fuel Gas.

PMID- 19600902
TI  - Some Preventive Measures to Diminish the Number of Abortions and Still-Births.

PMID- 19600901
TI  - Disinfection in Yellow Fever.

PMID- 19600903
TI  - Notes on the Frequency of Certain Diseases through Defects in Oxidation at High
      Altitude.

PMID- 19600904
TI  - The Prevention of Blindness by the Adoption of Laws Compelling Hygienic
      Precautions.

PMID- 19600905
TI  - Remarks on the Dairies in the Capital of the Mexican Republic.

PMID- 19600907
TI  - Yellow Fever is a Preventable Disease.

PMID- 19600906
TI  - Relations of Laboratories to Public Health.

PMID- 19600908
TI  - Studies on the Distribution of Certain Varieties of the Diphtheria Bacillus.

PMID- 19600909
TI  - Branching Diphtheria Bacilli.

PMID- 19600911
TI  - A Streptothrix Form Isolated from Water and Resembling the Diphtheria Bacillus.

PMID- 19600910
TI  - Influence of Forests on Public Health.

PMID- 19600912
TI  - Notes on Bacterial Water Analysis.

PMID- 19600913
TI  - The Significance of Certain Gas-Producing Bacteria of Non-Colon Type in Sanitary
      Water Analysis.

PMID- 19600914
TI  - On the Question of Standard Methods for the Determination of the Numbers of
      Bacteria in Waters.

PMID- 19600915
TI  - Some Points on the Differentiation and Classification of Water Bacteria.

PMID- 19600916
TI  - The Observation of Odor as an Essential Part of Water Analysis.

PMID- 19600917
TI  - Synopsis of a Paper upon "The Action of Water upon Lead, Tin and Zinc, with
      Especial Reference to the Use of Lead Pipes with Massachusetts Water Supplies.".

PMID- 19600918
TI  - The Iodometric Determination of Small Quantities of Carbon Monoxide.

PMID- 19600919
TI  - The Making of Agar-Agar.

PMID- 19600920
TI  - Outline of the Work Carried on in the New York State Pathological Laboratory on
      the Etiology of Cancer.

PMID- 19600921
TI  - Modifications of the Postal Regulations Recommended by the Colorado State Board
      of Health.

PMID- 19600922
TI  - Notes on the Reaction at which the Maximum Growth of Bacteria Occurs in Liquid
      Media.

PMID- 19600923
TI  - Disinfection and Individual Prophylaxis against Infectious Diseases.

PMID- 19600924
TI  - The Relation of Forests to Public Health.

PMID- 19600925
TI  - University Laboratories in Relation to the Investigation of Public Health
      Problems and to Commercial Work.

PMID- 19600927
TI  - Report of the Committee on the Cause and Prevention of Contagious Diseases.

PMID- 19600926
TI  - Some Personal Experiences in Disinfection.

PMID- 19600928
TI  - Prevention of Contagious Diseases.

PMID- 19600930
TI  - Report of the Committee on Car Sanitation.

PMID- 19600929
TI  - President's Address.

PMID- 19600931
TI  - Supplementary Report on Car Sanitation.

PMID- 19600932
TI  - Report of the Committee on the Pollution of Public Water Supplies.

PMID- 19600933
TI  - Report of the Committee on Disposal of Refuse Materials.

PMID- 19600935
TI  - A Scheme for Preventive Medicine.

PMID- 19600934
TI  - Report of Committee on Teaching of Hygiene and Granting Degrees of Doctor of
      Public Health.

PMID- 19600936
TI  - Remarks Concerning the Vice of Smoking Among Youths, and Suggestions As to the
      Means of Overcoming It.

PMID- 19600937
TI  - Necessity of the Hygienic Analysis of Milk when Used for the Artificial Feeding
      of Infants and Method of doing so with Rapidity and Certainty.

PMID- 19600938
TI  - Report of Section Committee on Bacteriology of Milk in its Sanitary Relations.

PMID- 19600939
TI  - Report of Committee on Disinfectants.

PMID- 19600940
TI  - Woman's Sanitary Work in Indianapolis.

PMID- 19600942
TI  - Are National Leprosaria in the United States Desirable?

PMID- 19600941
TI  - Report of Committee to Define "What Constitutes an Epidemic.".

PMID- 19600944
TI  - Investigation of Stream Pollution by the United States Geological Survey.

PMID- 19600943
TI  - Report of Committee on Animal Diseases and Animal Food.

PMID- 19600945
TI  - Our Domain's Most Threatening Danger.

PMID- 19600946
TI  - Pages from a Sanitarian's Note Book.

PMID- 19600947
TI  - A Resume of the Recent Foreign Work of the Marine Hospital Service.

PMID- 19600948
TI  - Report of Committee on Transportation of Diseased Tissues by Mail.

PMID- 19600949
TI  - Report of Committee on the Etiology of Yellow Fever.

PMID- 19600950
TI  - Varieties of Colon Bacilli Isolated from Man and Animals.

PMID- 19600952
TI  - Variations of the Colon Bacillus in Relation to Public Health.

PMID- 19600951
TI  - Some Observations on Methods for the Detection of B. Coli Communis in Water.

PMID- 19600953
TI  - Preliminary Report of the Committee on Standard Methods of Water Analysis.

PMID- 19600954
TI  - The Rapid Diagnosis of Rabies.

PMID- 19600955
TI  - A Note on the Disinfectant and Deodorant Properties of Ammonium Persulphate.

PMID- 19600956
TI  - An Inquiry into the Role of the Domestic Animals in the Causation of Typhoid
      Fever.

PMID- 19600957
TI  - Recent Work on Tuberculosis.

PMID- 19600958
TI  - Thermal Death Point of the Tubercle Bacillus and its Relation to Commercial
      Pasteurization of Milk.

PMID- 19600959
TI  - Ninth Report on the Yellow Fever on the Coast of the Mexican Gulf.

PMID- 19600961
TI  - Report of the Committee on Steamship and Steamboat Sanitation.

PMID- 19600960
TI  - The Etiology of Yellow Fever-A Preliminary Note.

PMID- 19600962
TI  - New Quarantine Methods and Changes which are Called for in Marine Sanitation.

PMID- 19600964
TI  - Report of Committee on Cause and Prevention of Infectious Diseases.

PMID- 19600963
TI  - Elements of Defense against Infectious-Contagious Diseases, Possessed by the Port
      of Veracruz.

PMID- 19600965
TI  - Influence of Temperature on Vaccine Virus.

PMID- 19600966
TI  - The Only Certain Prophylaxis Against Smallpox Is Human Vaccine Which, If Well
      Inoculated, Does Not Transmit Infectious-Contagious Nor Diathetic Disease.

PMID- 19600967
TI  - Human Vaccine as a Prophylactic of Smallpox: Its Advantages and Disadvantages.

PMID- 19600969
TI  - Newark's (N. J.) Antitoxine Plant-Its Results and Cost.

PMID- 19600968
TI  - The Jenner Vaccine Well Preserved and Carefully Propagated is a Permanent
      Preservative against Smallpox.

PMID- 19600970
TI  - President's Address.

PMID- 19600972
TI  - The Legal Aspects of Water Pollution.

PMID- 19600971
TI  - Typhoid Fever Death Rates in American Cities.

PMID- 19600974
TI  - The Results of Yellow Fever Sanitation in Havana, Cuba, for the Year 1901 up to
      September 1st, Carried on upon the Basis that the Stegomyia Mosquito is the Sole
      Means of its Transmission.

PMID- 19600973
TI  - The Prevention of Yellow Fever.

PMID- 19600975
TI  - Practical Discussion of Yellow Fever.

PMID- 19600977
TI  - Fomites and Yellow Fever.

PMID- 19600976
TI  - Address of Welcome.

PMID- 19600979
TI  - A Brief Statement of the Sanitary Work So Far Accomplished in the Philippine
      Islands, and of the Present Shape of Their Sanitary Administration.

PMID- 19600978
TI  - Tenth Report on Yellow Fever in Mexico.

PMID- 19600980
TI  - Sanitation in Porto Rico.

PMID- 19600981
TI  - Response of the President to the Address of Welcome.

PMID- 19600982
TI  - Vaccinal Immunization from the Health Officer's Standpoint.

PMID- 19600983
TI  - Remarks Intended to Show the Innocuous Character of Humanized Vaccine as a
      Preventative of Smallpox.

PMID- 19600984
TI  - Report of the Committee on Disposal of Refuse Materials.

PMID- 19600985
TI  - Refuse Disposal in Boston.

PMID- 19600987
TI  - Refuse Disposal in the District of Columbia.

PMID- 19600986
TI  - On the Progress of Public Health Organizations in the United States.

PMID- 19600988
TI  - The Bacterial Purification of Water by Freezing.

PMID- 19600990
TI  - Circular of the American Public Health Association Issued by the Committee on Car
      Sanitation.

PMID- 19600989
TI  - Report of the Committee on the Relation of Forestry to the Public Health.

PMID- 19600991
TI  - Report of the Committee on Cause, Prevention and Duration of Infectious Diseases.

PMID- 19600992
TI  - Present Status of Diphtheria.

PMID- 19600993
TI  - Typhoid Fever.

PMID- 19600995
TI  - Report of Sub-Committee on Standard Cultures and the Method of Using them.

PMID- 19600994
TI  - Report of Committee on Disinfectants and Disinfection.

PMID- 19600997
TI  - Report of the Committee on Public Health Legislation.

PMID- 19600996
TI  - Observations on the Practice of Disinfection in the Federal District of Mexico.

PMID- 19600998
TI  - Report of Committee on School Hygiene.

PMID- 19600999
TI  - Report of Committee on Transportation of Diseased Tissue by Mail.

PMID- 19601000
TI  - Notes on the Necessity of Attending to the Hygiene of the Mouth Amongst the
      Pupils of Schools.

PMID- 19601001
TI  - The Influence of School Life over Health.

PMID- 19601002
TI  - A Summary of a Paper on the Advisability of Entrusting to Physicians, and not to
      Teachers, the Medical Supervision of Pupils.

PMID- 19601003
TI  - Report of the Committee on Demography and Statistics in their Sanitary Relation.

PMID- 19601005
TI  - Summary of a Paper on Cremation in Relation to Sanitary Legislation.

PMID- 19601004
TI  - Some of the Causes of Infant Mortality in Nurseries and Asylums, and their
      Prevention.

PMID- 19601006
TI  - Some Results of the Army Canteen or post Exchange from the Standpoint of
      Discipline and Hygiene.

PMID- 19601007
TI  - Anti-Rabic Department of the Supreme Board of Health of Mexico.

PMID- 19601008
TI  - Report of the Committee on National Leper Homes.

PMID- 19601009
TI  - Report of Committee on Standard Methods of Water Analysis.

PMID- 19601010
TI  - Studies of Media for the Quantitative Estimation of Bacteria in Water and Sewage.

PMID- 19601011
TI  - Is the Colon Bacillus a Normal Inhabitant of the Intestines of Fishes?

PMID- 19601012
TI  - Some Common Bacteria in American Streams, Including Some New Species Isolated at
      New Orleans, Louisiana.

PMID- 19601013
TI  - The Significance of the Presence and Amount of Carbon Di-oxide in Potable Waters.

PMID- 19601014
TI  - Refined and Improved Antitoxin Preparations.

PMID- 19601015
TI  - Antitoxins and Agglutinins.

PMID- 19601016
TI  - Some Work on a Curative Serum for Typhoid Fever.

PMID- 19601017
TI  - Methods of Diagnosis in Glanders.

PMID- 19601018
TI  - The Viability of the Plague Bacillus in its Relations to the Public Health.

PMID- 19601019
TI  - Report of Committee on Animal Diseases and Animal Food.

PMID- 19601021
TI  - The Bacterial Contamination of City Milk-Is It Harmful? Should It Be Controlled
      by Health Authorities?

PMID- 19601020
TI  - Cultivation of the Bacillus Influenza.

PMID- 19601022
TI  - The Non-Nitrification of Septic Sewage in Contact Filters.

PMID- 19601023
TI  - Some Points in the Life History and in the Decomposition of Blue-Green Algae as
      Illustrated by Oscillaria Prolifica (with Samples).

PMID- 19601024
TI  - Hydrocyanic-Acid Gas in Public Health Work.

PMID- 19601025
TI  - Air Testing for Engineers.

PMID- 19601026
TI  - An Engineer's Kit for Water Inspection.

PMID- 19601027
TI  - Summary of a Paper Giving Some Facts Which Tend to Show That Bovine Tuberculosis
      Can Be the Source of the Same Disease in Man.

PMID- 19601028
TI  - Tuberculosis: Heredity.

PMID- 19601029
TI  - Summary of a Paper on Sanatoria for Consumptives.

PMID- 19601030
TI  - Report of Committee on Teaching of Hygiene and Granting of Diploma of Doctor of
      Public Health.

PMID- 19601031
TI  - Instruction in Hygiene for Architects and Engineers.

PMID- 19601033
TI  - Instruction in Hygiene for Veterinary Students.

PMID- 19601032
TI  - University Teaching in Hygiene.

PMID- 19601035
TI  - Sanitary Measures Proposed to the Mexican Railway Companies.

PMID- 19601034
TI  - President's Address.

PMID- 19601036
TI  - Report of the Committee on the Cause, Prevention, Period of Incubation and
      Duration of Infectious Diseases: A General Review.

PMID- 19601038
TI  - A Note Concerning the Transmission of Pathogenic Fungus by Flies and Mosquitoes.

PMID- 19601037
TI  - Period during which Contagious Diseases are Transmissible and Sick Persons are
      Dangerous to Healthy Persons Near Them.

PMID- 19601039
TI  - Report of Committee on Public Health Legislation.

PMID- 19601040
TI  - Report of the Committee on National Leper Homes.

PMID- 19601041
TI  - Report of Committee on "Dangers to the Public Health from Illuminating and Fuel
      Gas".

PMID- 19601042
TI  - Report of Committee on the Relative Immunizing Value of Human and Bovine Vaccine
      Virus.

PMID- 19601043
TI  - Address of Welcome.

PMID- 19601044
TI  - Results of Revaccination in Mexico.

PMID- 19601045
TI  - The Asepsis of Vaccine.

PMID- 19601046
TI  - Report of Committee on Sanitary Aid Societies.

PMID- 19601047
TI  - Response of President to Address of Welcome.

PMID- 19601048
TI  - Report of Committee on the Teaching of Hygiene and Granting a Diploma of Doctor
      of Public Health.

PMID- 19601049
TI  - Vital Statistics: A Plea for Actuarial Administration and Control of the Great
      Resources of Preventive Medicine.

PMID- 19601050
TI  - Opening Address.

PMID- 19601051
TI  - Co-Operation Essential to Progress in Vital Statistics.

PMID- 19601052
TI  - Joint Resolution in re Registration of Vital Statistics.

PMID- 19601053
TI  - Report of Committee on Disinfection and Disinfectants.

PMID- 19601054
TI  - The Distribution of B. Diphtheriae and B. Tuberculosis in Rooms Occupied by
      Patients Suffering from these Diseases.

PMID- 19601056
TI  - Experiments in Disinfection with Formaldehyd Gas.

PMID- 19601055
TI  - Report of Committee on Disposal of Refuse Materials.

PMID- 19601057
TI  - The Method of Transmission of Yellow Fever from Man to Man.

PMID- 19601058
TI  - Reasons for Believing that the Only Way in Nature for Yellow Fever to be
      Contracted by Man is from the Mosquito.

PMID- 19601059
TI  - Report on Yellow Fever in the Republic of Mexico from October 31, 1901, to
      September 30, 1902.

PMID- 19601060
TI  - Reports on the Orizaba (Mexico) Yellow Fever Epidemics.

PMID- 19601061
TI  - The Disinfection of Railroad Cars as a Precautionary Measure against the
      Propagation of Yellow Fever by Mosquitoes.

PMID- 19601062
TI  - An Official Examination of the Waters of the United States.

PMID- 19601064
TI  - On the Relative Importance of Public Water Supplies and Other Factors in the
      Causation of Typhoid Fever.

PMID- 19601063
TI  - The Water Supply of New Orleans and its Improvement.

PMID- 19601066
TI  - Dirt, Disease and the Health Officer.

PMID- 19601065
TI  - Refuse Disposal in Montreal.

PMID- 19601067
TI  - Tuberculosis and Agricultural Colonies.

PMID- 19601069
TI  - Wet Nurses-Their Hygienic Importance.

PMID- 19601068
TI  - Causes and Preventives of Infant Mortality.

PMID- 19601071
TI  - Report of the Committee on Standard Methods of Water Analysis. Third Report of
      Progress.

PMID- 19601070
TI  - Hygiene of the Sight.

PMID- 19601072
TI  - Bacillus Coli Communis.

PMID- 19601074
TI  - On Certain Precautions Required in Making and Interpreting the So-Called "Colon
      Test" for Potable Waters.

PMID- 19601073
TI  - Notes on B. Coli and Allied Forms, with Special Reference to the Neutral-Red
      Reaction.

PMID- 19601075
TI  - The Colon Bacillus in Ground Waters.

PMID- 19601076
TI  - On the Practical Value of Presumptive Tests for Bacillus Coli in Water.

PMID- 19601077
TI  - Experiments with the Neutral-Red Test for Bacillus Coli in the Examination of
      Water Supplies.

PMID- 19601078
TI  - The Use of Immune Serum in the Separation of Typhoid Fever from Colon Bacilli.

PMID- 19601079
TI  - Laboratory Methods Used during the New Orleans Water Purification Investigation.

PMID- 19601080
TI  - A Study of the Methods Employed for Determining the Amount of Oxygen Consumed
      from Permanganate by the Impurities in Water and Sewage.

PMID- 19601081
TI  - The Occurrence of Tubercle Bacilli of Exalted Virulence in Man.

PMID- 19601082
TI  - The Collection and Disposal of Garbage in Providence, R. I.

PMID- 19601083
TI  - A Report of the Bacteriological and Pathological Findings in a Fatal Case of
      Dysentery at Tuckahoe, with Additional Notes upon the Serum Reactions Obtained
      with the Blood from a Number of the Dysentery Cases.

PMID- 19601085
TI  - Notes on Morphology.

PMID- 19601084
TI  - Observations on the Morphology of B. Diphtheriae, B. Pseudo-diphtheriae and B.
      Xerosis.

PMID- 19601086
TI  - A Proposed Classification and Method of Graphical Tabulation of the Characters of
      Bacteria.

PMID- 19601087
TI  - On the Classification and Identification of Bacteria with a Description of the
      Card System in Use at the Lawrence Experiment Station for Records of Species.

PMID- 19601089
TI  - Notes on Formaldehyde.

PMID- 19601088
TI  - An Examination into the Value of Certain Antiseptics Used for the Preservation of
      Antitoxic and Other Immune Serums.

PMID- 19601090
TI  - Disposal of Refuse in the City of Buffalo, New York.

PMID- 19601091
TI  - Air Testing in Tunnel Construction.

PMID- 19601092
TI  - A Simple Method for Rapid and Accurate Weighing.

PMID- 19601094
TI  - On the Germination of the Spores of B. Subtilis and B. Megatherium.

PMID- 19601093
TI  - Collodion Sacs.

PMID- 19601095
TI  - The Supposed Identity of Human and Avian Diphtheria.

PMID- 19601096
TI  - Demonstration of a Method for Capping Bottles Containing Certified Milk.

PMID- 19601097
TI  - Report upon the Disposal of Refuse Materials in Cincinnati, Ohio.

PMID- 19601099
TI  - Street Hygiene in Veracruz and City of Mexico.

PMID- 19601098
TI  - Report on the Disposal of the Refuse of New York City.

PMID- 19601100
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19601102
TI  - Report of the Committee on the Causes and Prevention of Infant Mortality.

PMID- 19601101
TI  - President's Address.

PMID- 19601104
TI  - Report of Committee on Sanitary Aid Societies.

PMID- 19601105
TI  - Report of the Committee on Disposal of Garbage and Refuse.

PMID- 19601103
TI  - Report of the Committee on the Teaching of Hygiene and the Conferring of a Degree
      in Public Health.

PMID- 19601107
TI  - The Sanitary Disposal of Municipal and Institutional Waste by Cremation.

PMID- 19601106
TI  - Address of Welcome.

PMID- 19601108
TI  - Some Statistics of Garbage Disposal for the Larger American Cities in 1902.

PMID- 19601109
TI  - Report of Committee on Disposal of Industrial Wastes.

PMID- 19601110
TI  - Report of the Committee on Car Sanitation.

PMID- 19601112
TI  - Transportation of Persons Sick with Transmissible Diseases.

PMID- 19601111
TI  - Address of Welcome.

PMID- 19601113
TI  - On Car Sanitation in the Republic of Mexico.

PMID- 19601115
TI  - Report of the Committee on Animal Diseases and Animal Food.

PMID- 19601114
TI  - Pertaining to the Transportation of the Dead.

PMID- 19601117
TI  - Some Indications that may Serve for the Better Utilization of the Results Derived
      from a Comparison of the Principal Causes of Death in the Cities that Apply the
      International Nomenclature.

PMID- 19601116
TI  - Report of Committee on Demography and Statistics in their Sanitary Relation.

PMID- 19601118
TI  - Report of Committee on Disinfection and Disinfectants.

PMID- 19601119
TI  - Disinfection in Mexico.

PMID- 19601120
TI  - Experimental Study of Hydrocyanic Acid as an Insecticide.

PMID- 19601122
TI  - Immigration and the Public Health.

PMID- 19601121
TI  - Remarks on the Preparation of Vaccine Virus.

PMID- 19601123
TI  - Factors Operative in the Spread of a Cholera Epidemic and the Management of the
      Same from a Quarantine Standpoint.

PMID- 19601124
TI  - A National Institute of Hygiene.

PMID- 19601125
TI  - Measures for Restraining the Propagation of Venero-Syphilitic Diseases.

PMID- 19601126
TI  - The Floors of Hospital Wards, considered from the Standpoint of Asepsis and
      Antisepsis.

PMID- 19601127
TI  - Hygiene of the Eyes in the Mexican Schools.

PMID- 19601128
TI  - Something about the Bacteriology and Clinical History of Plague.

PMID- 19601129
TI  - The Relation between Human and Bovine Tuberculosis.

PMID- 19601130
TI  - The Development of American Bacteriology.

PMID- 19601131
TI  - Four Years' Experience in an Attempt to Make a Bacterial Count of 100,000
      Bacteria per CC., a Standard for Municipal Milk Supply.

PMID- 19601132
TI  - The Release of Quarantine in Diphtheria.

PMID- 19601133
TI  - Report of Committee on Laboratory Tests of the Efficiency of Water Filters.

PMID- 19601134
TI  - The Effect of Lemon Juice in the Mixture Known as Lemonade upon Typhoid-Polluted
      Water.

PMID- 19601136
TI  - A Simple Method for the Routine Detection of the Colon Bacillus in Water.

PMID- 19601135
TI  - Report of the Committee on the Significance of B. Coli in Water Supplies.

PMID- 19601138
TI  - A Differential Test for Typhoid and Colon Bacilli.

PMID- 19601137
TI  - The Bacterial Examination of 104 Samples of Water, together with a Detailed Study
      of the Colon Bacillus.

PMID- 19601139
TI  - On Some Cultural Relations and Antagonisms of Bacillus Coli and Houston's Sewage
      Streptococci; with a Method for the Detection and Separation of these Micro
      Organisms in Polluted Water.

PMID- 19601140
TI  - On the Value of Tests for Bacteria of Specific Types as an Index of Pollution.

PMID- 19601141
TI  - Report of Committee on Etiology of Yellow Fever.

PMID- 19601142
TI  - Report of Committee on Bacillus Tuberculosis in Man and Animals.

PMID- 19601143
TI  - A Test of the Immunity of Cattle Inoculated with Tuberculosis Over-Against a
      Natural Exposure.

PMID- 19601145
TI  - Report of the Committee on Resolutions on the Death of Dr. Wyatt Johnston.

PMID- 19601144
TI  - The Passage of Tubercle Bacilli through the Normal Intestinal Wall. A Preliminary
      Report.

PMID- 19601146
TI  - Reflections on the Desirability of an Agreement between the Sanitary Authorities
      of Adjoining Countries for Mutual Defense against Transmissible Diseases.

PMID- 19601147
TI  - Comments on the Report of the Committee on the Etiology of Yellow Fever.

PMID- 19601148
TI  - Some Characteristics of the Stegomyia Fasciata which Affect its Conveyance of
      Yellow Fever.

PMID- 19601150
TI  - New Aspects of Yellow Fever Etiology Arising from Experimental Findings of the
      Last Three Years.

PMID- 19601149
TI  - Period of the Disease in Man during which Yellow Fever can be Transmitted to the
      Mosquito.

PMID- 19601151
TI  - Concerning the Geographic Distribution of the Yellow Fever Mosquito.

PMID- 19601153
TI  - Quarantine Regulations should be Based against Yellow Fever upon the Doctrine
      that it is Only Conveyed by the Mosquito.

PMID- 19601152
TI  - The Mosquitoes in Mexico City.

PMID- 19601155
TI  - Report of Committee on Canteens in Armies.

PMID- 19601154
TI  - Report of Committee on the Purification of Water Supplies.

PMID- 19601156
TI  - President's Address.

PMID- 19601158
TI  - Report of the Committee on Tuberculosis.

PMID- 19601157
TI  - Upon the Practical Utility of a Medical Board to Aid Local Sanitary Authorities
      in the Investigation of Infectious Diseases.

PMID- 19601159
TI  - Supplemental Report of Committee on Tuberculosis.

PMID- 19601160
TI  - Measures to be Adopted in the Struggle against Tuberculosis.

PMID- 19601161
TI  - The Anti-Tuberculosis League of Havana and its Work.

PMID- 19601162
TI  - Report of the Committee on the Bacillus Tuberculosis in Man and Animals.

PMID- 19601163
TI  - Report of Committee on Demography and Statistics in their Sanitary Relation.

PMID- 19601164
TI  - The Teaching of Hygiene in Colleges and Normal Schools.

PMID- 19601166
TI  - Report of Committee on Hygiene of Dress.

PMID- 19601165
TI  - Report of Committee on Purification and Preservation of Public Water Supplies.

PMID- 19601167
TI  - Social Hygiene.

PMID- 19601168
TI  - Report of Committee on Control of Milk Supplies in Large Cities.

PMID- 19601169
TI  - The Need of a Good Distribution and Inspection of Milk.

PMID- 19601170
TI  - Infantile Alimentation. Parallel between the Lactation by Nurses and by
      Artificial Means.

PMID- 19601171
TI  - Federal Control of Vaccine Virus.

PMID- 19601172
TI  - Experiment and Experience in the Production of Animal Vaccine.

PMID- 19601173
TI  - On the Necessity of Vaccination and Revaccination of Individuals who have
      Suffered from Smallpox.

PMID- 19601174
TI  - New Facts that Tend to Demonstrate the Superiority of Humanized over Animal
      Vaccine, for the Prophylaxis of Smallpox.

PMID- 19601175
TI  - Yellow Fever in Mexico.

PMID- 19601176
TI  - Experimental Study on the Acclimation of the Stegomyia Fasciata Mosquito in
      Mexico City.

PMID- 19601177
TI  - The Bubonic Plague in the Port of Mazatlan, State of Sinaloa, Republic of Mexico.

PMID- 19601179
TI  - Hygienic Conditions of Vera Cruz; Present and Future.

PMID- 19601178
TI  - The Actual Sanitary Conditions in Havana and the Further Requirements for their
      Improvement.

PMID- 19601180
TI  - A Practical Test of the Copper Sulphate Method for the Removal of Micro-Organisms
      from Water.

PMID- 19601181
TI  - Chairman's Address, Laboratory Section.

PMID- 19601183
TI  - Report of Committee on the Relation of Protozoa to Disease; in Particular "Amoeba
      Coli.".

PMID- 19601182
TI  - Emil Alexander de Schweinitz, Born 1864, Died 1904.

PMID- 19601184
TI  - Results of Studies of Variola in Cleveland, Ohio.

PMID- 19601185
TI  - An Unusual Channel of Infection with the Bacillus Shigae.

PMID- 19601186
TI  - Purification of the St. Louis Water Supply by Using Ferrous Sulphate and Calcium
      Hydroxide as a Coagulant, followed by Plain Sedimentation.

PMID- 19601187
TI  - The Use of Sulphate of Copper Alone, and in Combination with Lime for the
      Destruction of Mosquito Larvae-as a Deodorant, and as a Disinfectant.

PMID- 19601188
TI  - Report of the Committee on Disinfection and Disinfectants.

PMID- 19601190
TI  - The Disinfection of Palm Leaf and Other Huts.

PMID- 19601189
TI  - The Disinfection of School Books.

PMID- 19601191
TI  - Report of Committee on the Infectious Period of Communicable Diseases.

PMID- 19601193
TI  - The Sources of Infection.

PMID- 19601192
TI  - A Tribute to Carlos J. Finlay for his Distinguished Services to Science and
      Humanity in the Discovery of the Mode of Propagation of Yellow Fever.

PMID- 19601194
TI  - Diphtheria Infection in Minnesota-Recent Experiences with the Disease in School
      Children and in Institutional Epidemics.

PMID- 19601195
TI  - Co-ordinated Specialism in Public Health Work.

PMID- 19601196
TI  - The Distribution of B. Coli in the Waters of Lake Erie, near Cleveland.

PMID- 19601198
TI  - The Readjustment of Education and Research in Hygiene and Sanitation.

PMID- 19601197
TI  - The Ground Waters of Vermont from a Chemical and Bacteriological Standpoint.

PMID- 19601199
TI  - Education of and Co-operation with the General Public in Health Work.

PMID- 19601201
TI  - Present Regulations or Laws as to Qualifications and Methods of Appointment for
      (a) Executive, and (b) Technical Health Officials.

PMID- 19601200
TI  - The Double Allegiance of the Medical Officer of Health.

PMID- 19601202
TI  - Laws concerning Teaching Hygiene.

PMID- 19601203
TI  - Sanitary Conferences and Schools of Instruction.

PMID- 19601204
TI  - The Work of the Health Education League of Boston.

PMID- 19601205
TI  - Graduate and Undergraduate Instruction in Hygiene in Universities and Medical
      Colleges-Special Diplomas in Public Health.

PMID- 19601206
TI  - Teaching of Hygiene in Elementary Schools.

PMID- 19601207
TI  - Experiments on the Purification of Boston Sewage.

PMID- 19601209
TI  - Physical Exercises in the Schools.

PMID- 19601208
TI  - Methods for Securing Greater Uniformity in the Instruction and Co-operation
      toward Public Health by Means of the Teaching of Hygiene to the Children in
      School.

PMID- 19601210
TI  - Influence of Different Kinds of Handwriting on the Hygienic Posture and
      Deformities of School Children.

PMID- 19601211
TI  - The Dissemination of Tuberculosis as Affected by Railway Travel.

PMID- 19601212
TI  - A Few Points Relating to Car Sanitation.

PMID- 19601214
TI  - Some General Considerations on the Pathology of Smallpox.

PMID- 19601213
TI  - On Car Sanitation in Mexico.

PMID- 19601215
TI  - The Pathology and Etiology of Human Vaccinia.

PMID- 19601216
TI  - Further Experiments with Vaccine Virus.

PMID- 19601217
TI  - Preservation and Method of Administering Humanized Vaccine in Mexico.

PMID- 19601219
TI  - Quarantine, the Delirium Ferox of American Sanitation.

PMID- 19601218
TI  - The Restriction of Contagious Diseases in Cities.

PMID- 19601220
TI  - Modification of Present Port Inspection.

PMID- 19601221
TI  - Review of Disinfection for 1904-1905.

PMID- 19601222
TI  - Lessons to be Learned from the Present Outbreak of Yellow Fever in Louisiana.

PMID- 19601223
TI  - Some New Points in the Etiology and Symptomatology of Yellow Fever.

PMID- 19601224
TI  - Yellow Fever in Mexico.

PMID- 19601225
TI  - The Cause, Course, Prevention, and Treatment of Beriberi.

PMID- 19601226
TI  - Industrial Wastes and Their Sanitary Significance.

PMID- 19601227
TI  - Boston Day Camp for Tuberculosis.

PMID- 19601228
TI  - The Relation of Milk to Typhoid Fever in New York City.

PMID- 19601230
TI  - The Relation of Animal Life to Human Disease.

PMID- 19601229
TI  - A Study of Associative Action of Bacteria in the Souring of Milk.

PMID- 19601232
TI  - A Disease of Cattle in Mexico.

PMID- 19601231
TI  - The Federal Meat-inspection Service.

PMID- 19601233
TI  - A Consideration of Some of the Problems and Difficulties of Bacteriological
      Diagnosis.

PMID- 19601234
TI  - The Communicability of Cerebro-spinal Meningitis.

PMID- 19601235
TI  - Prevention of Dampness in Houses.

PMID- 19601236
TI  - The Preservation of Food with Antiseptics.

PMID- 19601237
TI  - Disposition of Municipal Refuse: American Conditions Illustrated by Data from
      Representative Cities.

PMID- 19601238
TI  - Report of Committee on Necrology.

PMID- 19601240
TI  - Sanitary Inspection versus Sanitary Analysis.

PMID- 19601239
TI  - The Pollution of Oysters.

PMID- 19601241
TI  - Upon the Use of Copper Sulphate in Water Supplies.

PMID- 19601243
TI  - The Effect of Copper Sulphate upon the Bacteriological and Chemical Constituents
      of Large Bodies of Water.

PMID- 19601242
TI  - Experiments on the Storage of Typhoid Infected Water in Copper Canteens.

PMID- 19601244
TI  - Some Observations upon the Agglutination of Bacteria.

PMID- 19601245
TI  - Comparative Studies of Diplococci Decolorized by Gram's Method, Obtained from the
      Spinal Fluid and from the Nares of Cases of Epidemic Cerebro-Spinal Meningitis.

PMID- 19601247
TI  - The Practical Advantages of the Gooch Crucible in the Determination of the Total
      and Volatile Suspended Matter in Sewage.

PMID- 19601246
TI  - A Method for the Direct Determination of Organic Nitrogen by the Kjeldahl
      Process.

PMID- 19601248
TI  - The Resistance to Decomposition of Certain Organic Matters in Sewage.

PMID- 19601249
TI  - The Collection and Preservation of Samples of Sewage for Analysis.

PMID- 19601250
TI  - A Ready Method for Preparing a Silica Turbidity Standard.

PMID- 19601252
TI  - Experience with the Use of a Nonbasic Alum in Connection with Mechanical
      Filtration.

PMID- 19601251
TI  - The Solubility of Calcium Carbonate and of Magnesium Hydroxide and the
      Precipitation of these Salts with Lime Water.

PMID- 19601253
TI  - The Use of Copper Sulphate in Water Filtration.

PMID- 19601254
TI  - On the Bactericidal Action of Copper.

PMID- 19601255
TI  - Notes in Regard to the Determination of Copper in Water.

PMID- 19601256
TI  - The Frequent Occurrence of Meningococci in the Nasal Cavities of Meningitis
      Patients and of those in Direct Contact with them.

PMID- 19601257
TI  - A Notable Source of Error in Testing Gaseous Disinfectants.

PMID- 19601258
TI  - Methods of Bacteriological Examination of Milk.

PMID- 19601260
TI  - A Device for Filtering Toxins, etc., by the Use of Water Pressure.

PMID- 19601259
TI  - Suggestions for Changes in the Schedules for Making Broth, Gelatin, and Agar,
      Recommended in the Last Report of the Committee on Standard Methods of Water
      Analysis.

PMID- 19601261
TI  - The Fermentation Tube in the Study of Anaerobic Bacteria with Special Reference
      to Gas Production and the Use of Milk as a Culture Medium.

PMID- 19601262
TI  - Source and Significance of Nitrites in Streams.

PMID- 19601263
TI  - The Use of Histological Methods in the Rapid and Certain Diagnosis of Smallpox.

PMID- 19601264
TI  - A Field Kit for Preliminary Water Survey.

PMID- 19601265
TI  - The Need for Uniform Methods in the Sanitary Examination of Milk.

PMID- 19601266
TI  - Discussion of Papers.

PMID- 19601267
TI  - Constitution of the Laboratory Section of the American Public Health Association.

PMID- 19601268
TI  - Temporary Alteration of Character of an Organism Belonging to the Colon Group.

PMID- 19601269
TI  - The Longevity of Bacillus Typhosus in Natural Waters and in Sewage.

PMID- 19601271
TI  - The Relative Applicability of Current Methods for the Determination of
      Putrescibility in Sewage Effluents.

PMID- 19601270
TI  - On the Relation between Oxygen in Water and the Longevity of the Typhoid
      Bacillus.

PMID- 19601272
TI  - A Comparative Review of Current Methods for the Determination of Organic Matter
      in Sewage.

PMID- 19601274
TI  - The Way to Stamp out Malarial Fevers.

PMID- 19601273
TI  - Address of the President.

PMID- 19601275
TI  - Something about the Etiology of Malarial Disease.

PMID- 19601276
TI  - Prophylaxis of Paludic Diseases.

PMID- 19601277
TI  - Action of the State against Tuberculosis.

PMID- 19601278
TI  - Organized Sanitary Work in Dealing with Overcrowding and Pauperism, Due to
      Immigration.

PMID- 19601279
TI  - The Essentials of the Crusade against Tuberlosis.

PMID- 19601280
TI  - The Relation of the Physician to the Tuberculosis Problem.

PMID- 19601281
TI  - The Spread of Tuberculosis through Factory Skim Milk.

PMID- 19601282
TI  - The Problem of City Milk Supplies.

PMID- 19601283
TI  - The Dairy Industry in its Relation to the Gastro-Intestinal Organs of Young
      Children and Convalescents from Certain Affections of the Same Organs.

PMID- 19601284
TI  - The Water Supply of Cities.

PMID- 19601285
TI  - Drinking Water in Relation to Typhoid Fever in Rural Communities.

PMID- 19601287
TI  - A Few Bacteriological Notes that will Confirm the Existence of Typhoid Fever in
      Mexico: Work of the National Institute of Bacteriology.

PMID- 19601286
TI  - Notes on the Determination of Iron.

PMID- 19601288
TI  - Result of Revaccination in Mexico.

PMID- 19601289
TI  - The Jenner Vaccine: It is Necessary to Establish Obligatory Revaccination in
      Mexico.

PMID- 19601290
TI  - Anchylostomiasis in Mexico.

PMID- 19601291
TI  - The Prophylaxis of Typhus.

PMID- 19601292
TI  - The Rains and Typhus.

PMID- 19601293
TI  - The Bubonic Plague: Rules for Defense against its Importation and for its
      Suppression if Developed in the Form of an Epidemic.

PMID- 19601294
TI  - The "Mal del Pinto" from a Hygienic Point of View.

PMID- 19601295
TI  - Ametropia in its Relations to Ocular Hygiene.

PMID- 19601296
TI  - Trachoma in Mexico.

PMID- 19601297
TI  - A Case of Recurrent Fever Observed in Havana.

PMID- 19601298
TI  - Program of Sanitary Health Works in the Valley and City of Mexico.

PMID- 19601300
TI  - Public Health and Prophylaxis of Diseases.

PMID- 19601299
TI  - Evolution of the Hygienic Conditions of the City of Mexico during the Last
      Fifteen Years.

PMID- 19601301
TI  - The New School Buildings in the City of Mexico.

PMID- 19601302
TI  - Sanitary Inspection of Dwelling Houses in the City of Mexico.

PMID- 19601303
TI  - The Problems of Car Sanitation.

PMID- 19601304
TI  - Report on the Condition and Prospects of Vital Statistics in the United States.

PMID- 19601305
TI  - Contribution to the Study of Problems of National and International Sanitary
      Legislation.

PMID- 19601306
TI  - Observations on the Census and Mortality Tables of the City of Mexico.

PMID- 19601308
TI  - Veterinary Hygiene: Applied to the Protection of Man against Zoonosis.

PMID- 19601307
TI  - Notes on Preventive Measures against Hydrophobia.

PMID- 19601309
TI  - Yellow Fever.

PMID- 19601311
TI  - A Short Account of the Sanitary Department of the Isthmian Canal Commission.

PMID- 19601310
TI  - To what Extent are Infected Mosquitoes Present on Shipboard?

PMID- 19601312
TI  - The Diagnosis and Prevention of Yellow Fever.

PMID- 19601313
TI  - Brief Notes on the Propagation of Yellow Fever.

PMID- 19601314
TI  - The Origin of Sporadic Cases of Yellow Fever at Long Periods.

PMID- 19601315
TI  - The Yellow Fever Epidemic of 1905 in New Orleans.

PMID- 19601316
TI  - Notes on Yellow Fever.

PMID- 19601317
TI  - Notes on the Hygiene of Yellow Fever.

PMID- 19601318
TI  - Geography of Malaria in the Mexican Republic.

PMID- 19601319
TI  - On the Use of Methylene Blue in Testing Sewage Effluents.

PMID- 19601320
TI  - Liberation of Formaldehyde through the Agency of Calcium Carbide.

PMID- 19601321
TI  - The Liberation of Formaldehyde Gas from Solution by Means of Potassium
      Permanganate.

PMID- 19601322
TI  - 1. Sputum Shaking and Sedimenting Apparatus. 2. A Rabies Collecting Outfit.

PMID- 19601323
TI  - A New Mosquito Cage.

PMID- 19601324
TI  - The Action of Sunlight upon Bacteria with Special Reference to B. tuberculosis.

PMID- 19601325
TI  - The Application to a Soft-Water Sewage of Direct Processes for the Determination
      of Kjeldahl Nitrogen and Nitrogen as Free Aminonia.

PMID- 19601326
TI  - Some Data in Regard to the Comparative Disposition of Organic Matter by Sand,
      Contact and Sprinkling Filters.

PMID- 19601327
TI  - Dissolved Oxygen in Water: Some Preliminary Work on a Colorimetric Process.

PMID- 19601328
TI  - Observed Relations between Dissolved Oxygen, Carbonic Acid and Algae Growths in
      Weequahic Lake, Newark, N. J.

PMID- 19601329
TI  - The Pathogenicity of Streptococcus Lacticus.

PMID- 19601331
TI  - Air Supply Examination.

PMID- 19601332
TI  - Trypanasoma Lewisi in Mexico.

PMID- 19601330
TI  - The Excretion of Boric Acid from the Human Body.

PMID- 19601333
TI  - Notes on an Epizootical Disease in Rabbits.

PMID- 19601334
TI  - Diphtheria Bacilli in Well Persons in Mexico City.

PMID- 19601335
TI  - Experiments with Methods for the Rapid Detection of Gelatin Liquefaction in the
      Determination of B. Coli.

PMID- 19601336
TI  - A Study of House Disinfection and Reinfection.

PMID- 19601337
TI  - The Use of Lactose-Bile Medium in Water Analysis.

PMID- 19601339
TI  - Comparative Results Obtained by the Use of Lactose-Bile and Dextrose-Broth Media
      for the Detection of B. coli in Water.

PMID- 19601340
TI  - Sanitary Chemical Examination of Water Bacteria.

PMID- 19601338
TI  - Experience with Lactose-Bile Medium for the Detection of B. coli in Water.

PMID- 19601341
TI  - The Relative Importance of Streptococci and Leucocytes in Milk.

PMID- 19601343
TI  - The Comparative Value of Bacterial and Temperature Regulations for a City's Milk
      Supply.

PMID- 19601344
TI  - Comparison between Bacteriological Analysis of Air by the Plate Method and by
      Filters.

PMID- 19601342
TI  - Leucocyte Standards and the Leucocyte Content of Milks from Apparently Healthy
      Cows.

PMID- 19601345
TI  - The Agglutination Method of Diagnosis in the Control of Glanders.

PMID- 19601346
TI  - The Growth and Toxin Production of Bacillus diphtheriae upon Proteid-Free Media.

PMID- 19601347
TI  - President's Address.

PMID- 19601348
TI  - Water as One of the Principal Conveyors of "Mountain Fever", Typhus.

PMID- 19601349
TI  - The Prevention of Tuberculosis in the Primary Schools.

PMID- 19601350
TI  - The Outlook for a General System of Registration of Vital Statistics in the
      United States.

PMID- 19601351
TI  - The Action of a High Dry Climate in the Cure of Tuberculosis.

PMID- 19601352
TI  - Uncinariasis in Florida.

PMID- 19601353
TI  - Yellow Fever.

PMID- 19601354
TI  - Sanitary Records of Dwellings.

PMID- 19601355
TI  - Measures Relative to Immigration Adopted in Mexico.

PMID- 19601357
TI  - Immigration in Relation to Public Health.

PMID- 19601356
TI  - Social Ethics as Influenced by Immigration.

PMID- 19601358
TI  - Trachoma and Immigration.

PMID- 19601359
TI  - Ophthalmia Neonatorum: A Problem in Public Health.

PMID- 19601360
TI  - Leucocytes in Milk.

PMID- 19601361
TI  - Judging the Sanitary Condition of Dairies with the Aid of a Score Card.

PMID- 19601362
TI  - Construction and Care of Streets, from a Public Health Standpoint.

PMID- 19601363
TI  - The Public Road in its Relation to the Public Health.

PMID- 19601364
TI  - The Sanitarian's Responsibility to Embalmers.

PMID- 19601365
TI  - The Relation of Health Budgets to Health Efficiency.

PMID- 19601366
TI  - Meat Inspection of the Federal District.

PMID- 19601367
TI  - Report of Committee on Organization of a Section on Vital Statistics.

PMID- 19601369
TI  - Resolutions on the Death of Dr. Felix Formento.

PMID- 19601368
TI  - Report of Committee to Investigate and Report upon the Formation of a Section
      Composed of Municipal Health Officers.

PMID- 19601370
TI  - Resolutions on the Death of Dr. James Carroll.

PMID- 19601371
TI  - Report of the Advisory Council.

PMID- 19601372
TI  - Report of Committee on the Establishment of an Association Journal.

PMID- 19601373
TI  - Report of Committee on a National Department of Health for the Four Countries
      Represented in the Association.

PMID- 19601374
TI  - The Sources of Error in Bacterial Diphtheria Diagnosis.

PMID- 19601375
TI  - Diphtheria in the State of Jalisco, Mexico.

PMID- 19601376
TI  - Control of the Minor Infectious Diseases.

PMID- 19601377
TI  - A Few Measures for the Control of the So-called Minor Infectious Diseases.

PMID- 19601378
TI  - Contact Infection.

PMID- 19601379
TI  - Typhoid Fever at Knoxville, Tenn., and its Relation to the Water Supply.

PMID- 19601380
TI  - Majusi's observations and instructions on medicine and public health.

PMID- 19601381
TI  - The physician-surgeon Al-Zahrawi and the natural origins and manufacture of
      drugs.

PMID- 19601382
TI  - Arabic medicine and its impact on teaching and practice of the healing arts in
      the west.

PMID- 19601384
TI  - [On the occasion of the 155th anniversary of Michael Idvorsky Pupin's birth].

PMID- 19601383
TI  - Hermes Drug in La Grange: a pioneer Texas store.

PMID- 19601385
TI  - Staving off death: a case study of the pharmaceutical industry's strategies to
      protect blockbuster franchises.

PMID- 19601387
TI  - Using Medicare administrative data to conduct postmarketing surveillance of
      follow-on biologics: issues and opportunities.

PMID- 19601386
TI  - Is three a crowd or company?: Behind-the-counter drugs.

PMID- 19601388
TI  - Defending substantial equivalence: an argument for the continuing validity of the
      510(k) premarket notification process.

PMID- 19601389
TI  - FDA's dietary supplement CGMPs: standards without standardization.

PMID- 19601390
TI  - Revisiting Factor VIII cases: is it time for an agency adjudication system?

PMID- 19601391
TI  - Effect of garlic (Allium sativum) on nickel II or chromium VI induced alterations
      of glucose homeostasis and hepatic antioxidant status under sub-chronic exposure
      conditions.
AB  - Garlic (Allium sativum) has a profound effect in reducing plasma glucose and
      increasing serum insulin in diabetic rats. We studied the effect of a garlic
      extract on nickel- or chromium-induced alteration of plasma glucose and hepatic
      glycogen levels and anti-oxidant status in rats. Adult male albino rats (n=36)
      divided into six groups of six animals each were treated as follows: Group I,
      untreated controls; Group II, fresh aqueous homogenate of garlic; Group III,
      nickel sulfate; Group IV, nickel sulfate + garlic; Group V, potassium dichromate;
      Group VI, potassium dichromate + garlic. In Groups IV and VI, the simultaneous
      administration of garlic abrogated a significant nickel- or chromium-induced
      increase in plasma glucose and decrease in liver glycogen. Nickel and chromium
      alone also increased lipid peroxide (LPO) and decreased glutathione levels, as
      well as the activity of superoxide dismutase (SOD), catalase, and glutathione
      peroxidase. Simultaneous garlic administration significantly reduced the LPO
      level and remarkably improved SOD activity. Hence, we postulate that the
      administration of garlic can prevent nickel II- or chromium VI-induced
      alterations in blood glucose homeostasis while exerting a hepatoprotective effect
      on glycogen levels and antioxidant status in male albino rats.

PMID- 19601392
TI  - Antihyperlipidemic effect of carvacrol on D-galactosamine-induced hepatotoxic
      rats.
AB  - Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic
      phenol occuring in many essential oils of the family Labiatae including,
      Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. The present study
      was designed to investigate the effect of carvacrol on D-galactosamine (D-GalN)
      induced hepatotoxicity in rats. D-GalN-hepatotoxic rats exhibited elevation in
      the serum bilirubin level and the activities of the hepatic marker enzymes
      aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and
      gamma glutamyl transpeptidase. In the plasma, increased levels of very low
      density lipoprotein cholesterol and low density lipoprotein cholesterol and
      decreased high density lipoprotein cholesterol were observed. Further, an
      increase in the levels of total cholesterol, phospholipids, triglycerides, and
      free fatty acids in the plasma and tissues of liver and kidney were observed in
      hepatotoxic rats. The administration of carvacrol for 21 days prevented and
      improved these parameters toward normalcy. The results suggest that carvacrol
      affords a significant hepatoprotective and hypolipidemic effect against D-GalN
      induced-rats.

PMID- 19601393
TI  - Effect of benzene extract of Ocimum sanctum leaves on cauda epididymis of albino
      rats.
AB  - In the present study, an attempt has been made to assess the effect of benzene
      extract of Ocimum sanctum leaves on ultrastructural changes in epithelial cells
      of the cauda epididymis and fertility of male albino rats. Wistar strain male
      albino rats were orally administered 250 mg/kg body weight of O. sanctum leaves
      followed by maintaining suitable controls for 48 days. The results indicate, in
      cauda epididymis, a significant reduction in epithelial height and nuclei
      diameter of epithelial cells. Cells showed vacuolization exhibiting of signs of
      degeneration. An ultra study revealed that, in general, the cauda epididymis was
      affected and in particular, the principal, clear and basal cells were highly
      disturbed. Further, the size of lipid droplets, mitochondria, Golgi complex,
      endoplasmic reticulum decreased, with an accumulation of lysosomal bodies. The
      fertility performance test showed no implantation in female rats mated with O.
      sanctum-treated male rats. The results suggest a probable dwindling of an
      androgen status/direct effect on the above observations.

PMID- 19601394
TI  - Role of the calcium channel in blastocyst implantation: a novel contraceptive
      target.
AB  - The proinflammatory blastocyst implantation cascade involves important mediators
      like prostaglandins (PG). The influx of calcium via the calcium channel acts as a
      trigger for the activation of the PG synthesis pathway. Hence, it was
      hypothesized that calcium channel blockers that are known to possess anti
      inflammatory activity may interfere with normal implantation. Pregnant Swiss
      albino mice (Mus musculus) were treated with diltiazem (1) 4 mg/kg, po on days 1
      6 of pregnancy, n=6/day) or (2) at the implantation site (25 microg/animal) via
      intrauterine injection in the right horn at 5:00 pm on day 4. The intact uterus
      was used to assay lipid peroxidation and superoxide dismutase activity as markers
      of membrane fluidity or to observe the day 15 fetus. Oral diltiazem treatment in
      therapeutic dosage before and during the implantation period did not cause any
      change in normal uterine milieu during the window of implantation. When injected
      into the uterine lumen 12-14 h before the average implantation time, however, a
      complete failure in implantation was observed. Thus, the site specific action of
      diltiazem may be blocking prostaglandin synthesis, hence causing implantation
      failure. Oral diltiazem treatment did not mimic this action, indicating that
      although orally safe in pregnancy in therapeutic dosage, calcium channel blockers
      may provide a new and yet unknown target in female contraceptive research.

PMID- 19601395
TI  - Respiratory distress and behavioral changes induced by sodium cyanide in the
      fresh water TELEOST, Cyprinus carpio (Linnaeus).
AB  - An acute toxicity (LC50) test using a static renewal bioassay method was
      conducted to determine the toxicity of sodium cyanide in freshwater exotic carp,
      Cyprinus carpio exposed for 96 h to different concentrations of sodium cyanide.
      The acute toxicity value was found to be 1 mg/L; one third of the LC50 (0.33
      mg/L) was selected as the sublethal concentration for subacute studies.
      Behavioral patterns were observed in lethal (1, 2, 3, and 4 d) and sublethal
      concentrations (1, 5, 10, and 15 d). Cyprinus carpio in toxic media exhibited
      irregular, erratic, and darting swimming movements, hyperexcitability, loss of
      equilibrium, and sinking to the bottom, which might be due to inhibition of
      cytochrome c oxidase activity and decreased blood pH. The combination of
      cytotoxic hypoxia with lactate acidosis depresses the central nervous system and
      myocardium, the most sensitive critical sites for anoxia, resulting in
      respiratory arrest and death. A decrease in oxygen consumption (-28.36 to 
      78.28%; -14.22 to -47.25%) was observed at both lethal and sublethal
      concentrations of sodium cyanide respectively. Fish at the sublethal
      concentration were found under stress, but that was not fatal.

PMID- 19601396
TI  - The role of mast cells in the genesis of acute manifestations following the
      intravenous injection of meperidine in dogs.
AB  - The effects of intravenous (iv) administration of the synthetic opioid analgesic
      meperidine in conscious dogs and their relation to histamine stored in mast cells
      were studied in comparison with those induced by compound 48/80, potent mast cell
      degranulator. When 48/80 (0.5 mg/ kg) and meperidine (10 mg/kg) were injected iv
      into conscious dogs, an acute brief period of yelling, flare reaction,
      scratching, hypersalivation, urination, defecation, and tachypnea occurred after
      a latency of 30-35 sec. In addition, meperidine-treated dogs showed marked
      sedation. Dogs whose histamine stores were depleted by 48/80 manifested none of
      those effects induced by meperidine except sedation. Likewise, pretreatment with
      meperidine prevented the effects of a subsequent injection of 48/80. Sedation
      appeared to be independent of the histamine-releasing effect of meperidine,
      whereas other effects elicited by its intravenous injection of the drug were
      suppressed by 48/80 and thus were probably mediated via released histamine. We
      concluded that the peripheral effects of meperidine show histamine dependency and
      mast cells are a potential important site for the peripheral actions of
      meperidine as well.

PMID- 19601397
TI  - Wound healing activity of flower extract of Calendula officinalis.
AB  - The effects of oral and topical application of Calendula officinalis flower
      extract on excision wounds made in rats were checked. The parameters assessed
      were the days needed for re-epithelization and percentage of wound closure. The
      hydroxy proline and hexosamine content in the granuloma tissue of the wound was
      also measured. The percentage of wound closure was 90.0% in the extract-treated
      group, whereas the control group showed only 51.1% on the eighth day of wounding
      (p < .01). The days needed for re-epithelization were 17.7 for the control
      animals; extract treatment at a dose of 20 or 100 mg/kg b.wt reduced the period
      to 14 and 13 days, respectively. A significant increase was observed in the
      hydroxy proline and hexosamine content in the extract-treated group compared with
      the untreated animals. The data indicate potent wound healing activity ofC.
      officinalis extract.

PMID- 19601398
TI  - Physical influences on right ventricular infarction and cardiogenic shock in
      acute myocardial infarction.
AB  - AIM: To determine if complicated acute myocardial infarction (AMI) is related to
      specific cosmophysical activities. METHODS: The study group included 1170
      patients who had undergone primary percutaneous coronary intervention (PCI) for
      AMI in 2000-2006. Geomagnetic and cosmic ray (neutron) activity (GMA, CRA) on the
      day of PCI were derived from international observatories. The findings were
      compared among patients with right ventricular infarction (RVI), cardiogenic
      shock, and uncomplicated AMI. RESULTS: Relative to the whole study period, the
      mean CRA was higher on days on which PCI was performed for RVI (n=123, 10.5%) (p
      = .0003) and cardiogenic shock (n=102, 8.72%) (p = .018). When the same artery
      was involved (LAD, RCA, CRX), CRA was significantly higher for complicated than
      for uncomplicated AMI (RVI group: p = .006, p = .00027, p = .014, c ardiogenic
      shock: p = .009, p = .029, p = .089, respectively). At the highest levels of GMA,
      more RVI cases were seen than cases of cardiogenic shock (p = .06). CONCLUSION:
      RVI and cardiogenic shock were associated with higher CRA than uncomplicated AMI.
      RVI occurred more often on days of high GMA than cardiogenic shock. Higher CRA
      may induce more myocardial damage in patients predisposed to AMI.

PMID- 19601399
TI  - Determination of sensitivity among various cardiovascular autonomic function
      tests in diabetic patients of Bijapur.
AB  - Eleven diagnosed diabetic patients and fifteen healthy age-matched controls were
      subjected to six standardized cardiovascular autonomic reflex function tests. The
      aim of the study was to identify the best sympathetic and parasympathetic
      autonomic function tests in diabetic patients and to determine their sensitivity.
      Several diabetic patients showed an abnormal response to various autonomic
      function tests. Among the three sympathetic tests studied, the coefficient of
      variation of all tests was found to vary and hence most sensitive test could not
      be determined. The heart-rate response to standing was found to be the most
      sensitive as it showed the lowest coefficient of variation. More parasympathetic
      than sympathetic tests showed abnormal responses in diabetics, particularly for
      heart rate responses to a deep breathing test. The results indicate that all
      autonomic function tests have to be performed for a proper evaluation/diagnosis
      of diabetic autonomic neuropathy.

PMID- 19601400
TI  - [Publish or perish: the scientific productivity of academics in the field of
      occupational medicine].
AB  - INTRODUCTION: A new Italian law aiming at improving and supporting research
      productivity establishes that evaluation of academic products is a requisite for
      accessing research funds,for acting as examiner for recruitments and for
      individual financial benefits. AIM: To analyse the scientific products of full
      professors of Occupational Medicine in Italian Universities in order to provide a
      framework for discussing a standard of productivity with objective metric
      parameters. POPULATION AND METHODS: Research products of the 40 full professors
      of Occupational Medicine indexed in the National Library of Medicine PubMed
      database were identified. By means of l0 different indicators, including the
      total number of papers, the papers published in journals included in the Journal
      Citation Reports (JCR), total Impact Factor (IF), the individual productivity of
      the last 5 years was measured. RESULTS: In the last 5 years 503 scientific
      products were published, 231 of which in JCR-indexed journals, with a mean
      individual IF = 16.741. The total number of papers indexed in PubMed, the number
      of papers included in JCR-indexed journals and the number of papers included in
      JCR-indexed journal of Public, Environmental & Occupational Health were
      associated with the overall number of authors (p < 0.001). This observation
      accounts for the relevance of the research group as a resource predicting
      qualitative and quantitative outputs. The total number of papers is inversely
      associated with age (p < 0.03). CONCLUSION: High productivity authors have an
      elevated number of products both in JCR-indexed journals (targeted to a small
      number of specialists in the field) and in PubMed-indexed journal (addressed to
      the broad audience of occupational health professionals). The productivity
      standard of academics of Occupational Medicine should take into account the
      overall research products within the Public Health field. In addition, the
      standard should be shared with that of academics of Hygiene and of Forensic
      medicine in order to address the recruitment policy in the Public Health field

PMID- 19601402
TI  - Risk of occupational radiation-induced cataract in medical workers.
AB  - BACKGROUND: ionizing radiation on the lens of the eye can produce a progressive
      cataract. Small cumulative doses, over a long time period, can produce adverse
      effects on the professional capabilities of health workers in the ionizing
      radiation zone. OBJECTIVES: The aim of this study was to ascertain whether
      occupational exposure to low levels of ionizing radiation can cause an increase
      in prevalence of cataract. METHOD: We compared a group with occupational
      cataract, consisting of 115 health workers in the ionizing radiation zone, and
      two control groups: a group of 100 health-care workers in the ionizing radiation
      zone, with a higher incidence of chromosomal aberrations, but without cataract;
      and another control group of 26 health-care workers with cataract, outside the
      zone; all risk factors for the development of cataract were considered: age, sex,
      diference in profession, duration of occupational exposure, years of service,
      level of blood sugar, blood pressure, arrhythmias, etc. RESULTS: A more
      significant incidence of cataract was found in workers in the ionizing radiation
      zone, where the relative risk was 4.6; p < 0.01. Radiology technicians showed the
      highest prevalence (63.5%), while physicians-radiologists and pneumologists were
      second (15.7%) and third (10.3%) respectively; nurses showed a 3.5% incidence and
      nuclear medicine department workers showed an incidence of only 1.7%. Other risk
      factors had an effect on the development of cataract (p < 0.05). CONCLUSIONS:
      Occupational exposure to low doses of ionizing radiation, together with other
      risk factors, is a significant cofactor in the occurrence of cataract as an
      occupational disease among x-ray exposed health care workers. The categories most
      at risk are radiology technicians,followed by radiologists.

PMID- 19601401
TI  - Digestive endoscopy and risk of upper limb biomechanical overload.
AB  - BACKGROUND: For several years the literature has reported a high prevalence of
      upper limb musculoskeletal disorders among medical staff carrying out digestive
      endoscopy. OBJECTIVES: The EPM research unit, in cooperation with the Italian
      Society of Digestive Endoscopy (SIED) and with the patronage of the Italian
      Society of Ergonomics (SIE), undertook research that would permit assessment of
      upper limb biomechanical overload using the OCRA method during gastroscopy and
      colonoscopy and, via a pilot study, collect health data on 179 workers employed
      in endoscopy services. RESULTS: Risk analysis showed slight exposure levels for
      the arm bearing the instrument and a medium-to-high exposure for the other arm.
      However, the study of diseases in this sample showed a higher prevalence than in
      the reference population not exposed to risk for the upper limbs and in
      particular in the hand-wrist area. CONCLUSIONS: Risk analysis highlighted
      possible ergonomic measures that would be easy to implement and which would
      significantly reduce the risk.

PMID- 19601403
TI  - [Improvement of a sedimentation method for measuring dispersion of fibres from
      asbestos cement roofs].
AB  - BACKGROUND: The present article is a follow-up of previous research, in which a
      sedimentation method was proposed to measure the dispersion of fibre bundles
      (primary pollution) from asbestos-cement roofs. OBJECTIVES: The aim of this study
      was to improve and standardize a screening method to evaluate asbestos bundle
      release from asbestos-containing materials. METHODS: An appropriate instrument
      (deposimetro) was used to passively sample asbestos on microscope slides by
      direct sedimentation. The microscopic analysis of samples was improved by the
      dispersion staining method, combined with the calculation of weight
      concentrations of asbestos per surface and time unit. The sampling efficiency was
      improved by introducing a new adhesive treatment of the microscope slides (85%
      stearyl alcohol, 15% octyldodecan) and a size cut-off restricting the counting
      method only to fibre bundles with diameters larger than 2 pm. RESULTS: The
      optimal sampling time was defined as 25-30 days without rain, extending the
      sampling time established in the previous investigation, and the optimal
      instrument position was defined at distances of 50 cm (vertical) and 0 cm
      (horizontal) from the roof edge. The effect of wind direction and velocity on
      asbestos release was also assessed, showing that wind gusts with a velocity of
      more than 10 m/s are mostly associated with dispersion peaks. CONCLUSIONS: A
      simple algorithm was proposed on the basis of field data (n=32) and 5 hazard
      classes were defined as a function of weight concentrations and asbestos type.
      The passive sampler is low in cost and is intended for use in large-scale surveys
      to identifY removal priorities.

PMID- 19601405
TI  - [Are teachers at risk for psychiatric disorders? Stereotypes, physiology and
      perspectives of a job prevalently done by women].
AB  - BACKGROUND: Teachers are one of the so-called helping professions which are
      strongly exposed to the "Burnout syndrome". Nonetheless, public opinion is still
      convinced teachers enjoy a privileged status and physicians most often ignore
      psychiatric disorders following burnout due to teaching-related stress. Indeed,
      although France recently issued a suicide warning among teachers, and psychiatric
      diagnosis among this profession almost doubled in Japan in ten years, only few
      studies have been published on the subject in peer-reviewed journals. OBJECTIVE
      AND METHODS: The present study was carried out by administering a questionnaire
      to 1295 teachers from ten different Italian regions aimed at evaluating teachers'
      conditions as well as their perception of work-related health risks. RESULTS AND
      CONCLUSIONS: The outcome showed that teachers are mostly unaware of work-related
      health risks, they are discouraged by their employers, perceive union support as
      highly insufficient and feel under attack by the mass media as well as by the
      public. Further, any attempt by the head teacher to protect teacher's health-
      mandatory according to recent Italian legislation--is frequently misinterpreted
      as mobbing, due to the lack of appropriate legal knowledge. Interestingly, the
      study population believed that investigating the link between menopause and
      depressive disorders among teachers was extremely useful. In fact, over 82% of
      teachers are women with a median age of approximately 50. Social stress among
      women has in fact increased greatly given the triple role played by fifty-year
      old teachers (mother of adolescents, care-giver for elderly parents and teacher).
      Lastly, general practitioners and psychiatrists need to be educated on
      psychiatric disorders due to teaching-related stress in order to achieve a
      correct diagnosis and treatment.

PMID- 19601404
TI  - [Work-related carpal tunnel syndrome. Motivations and results of a surveillance
      system].
AB  - BACKGROUND: Current statistics show that work-related carpal tunnel syndrome
      (CTS) has been increasing constantly over the last ten years. Nevertheless,
      available data on the incidence of CTS in the general population and on the
      occupational proportion of the aetiology of this disease suggest considerable
      underreporting of work-related cases, which reflects on the number of cases
      reported to INAIL (National Insurance Institute for Industrial Accidents) and
      does not give an accurate epidemiological picture of their origin and
      distribution. For this reason, in the course of a prevention programme of upper
      limb disorders due to biomechanical overload, a second experiment concerning CTS
      surveillance system was carried out by collecting self-reported information via
      postal questionnaires. The aim of this study was to estimate the prevalence of
      work-related cases in the selected group of the general population and to
      identify work tasks and factories with significant risk of CTS clusters. METHODS:
      From the hospital discharge lists of the Province of Brescia for 2001 and 2005,
      1558 surgical cases were selected, aged 18-65 years, excluding housewives (nearly
      25% of the total); thus 637 surgical cases were included in the study (68.6%
      female and 31.4% male). RESULTS AND CONCLUSIONS: Obesity frequency was observed
      to be higher in the sample than in the general population. This was not the case
      for diabetes. The probability of surgical CTS cases attributable to occupational
      exposure was estimated by dividing the 637 cases into three exposure
      categories:probable, possible and improbable with results of respectively 44.4%,
      36.6% and 19%; in the first category, the frequency among females was 78.8%. The
      CTS cases among females less than 40 years old was 40% in the probable exposure
      category versus 10% into the improbable exposure category. In the latter
      category, the prevalence of concomitant hand tendinitis was 11% versus 22% in the
      probable exposure category. Obese patients fell into the three occupational risk
      groups in the same proportion. Among the 283 STC cases considered as probable
      occupational exposure cases, only 11 were reported as required by law to the
      Occupational Health Service. Whereas a number of work tasks and work sectors with
      high risk factors were confirmed, there were relatively few factories with a
      possible presence of clusters, probably due to the small sample size compared to
      the general population and to the density of the factories potentially at risk.
      The epidemiological surveillance thus carried out provided more evidence
      confirming the serious underreporting of the work-related STC cases in a highly
      industrialised province and also provided useful information on the local
      situation regarding high-risk occupations, which need to be addressed via
      interventions of primary prevention should, possibly with greater involvement of
      the occupational physicians.

PMID- 19601407
TI  - [Are the operational directions presented in the consensus document "Workers with
      alcohol and drug addiction problems" practical?].

PMID- 19601406
TI  - [Comparative analysis of occupational health physician's duties based upon
      legislative decree 81/2008 art. 25 and upon the Ethics Code of the International
      Commission on Occupational Health].
AB  - INTRODUCTION: Ethical behaviour consists ofindividual choices inspired by
      knowledge and professional experience derived from the universally acknowledged
      ethical principles of beneficience/nonmaleficience, autonomy and justice.
      However, in spite of the unanimous consent on their universal importance, such
      principles do not usually have the strength of a law. AIM: The recently
      introduced Italian law on the protection of workers' health represents a novelty
      because it gives the Ethics Code of the International Commission on Occupational
      Health legal strength. This paper aims at examining article 25 of legislative
      decree 81/2008 by comparing the points of the Ethics Code and the Deontology Code
      of the Italian medical profession. RESULTS: The relationships between the 12
      points of paragraph 1 of article 25, the 26 points ofthe Code ofEthics and the 75
      articles of the Deontology Code are described with regard to the occupational
      health physician's duties (i) of collaboration with other occupational health
      professionals, (ii) of organization and execution of health surveillance, (iii)
      of recording, securing, transmitting of medical files on workers' health and (iv)
      of employee and employer information on the importance and meaning of health
      surveillance.

PMID- 19601408
TI  - You are the winners. Study finds association members more successful than
      nonmembers.

PMID- 19601409
TI  - 10 critical growth strategies healthcare executives must know.

PMID- 19601411
TI  - Achieving financial success through improved physician engagement: revenue
      enhancements can be realized with stronger relationships.

PMID- 19601410
TI  - Plugging revenue leaks: strengthening financial processes can lead to a better
      bottom line.

PMID- 19601412
TI  - The use and misuse of incentives. Incentives should always be carefully designed
      to avoid unintended consequences.

PMID- 19601413
TI  - Service recovery. The art of making things right when things go wrong.

PMID- 19601414
TI  - Should we fund this program? How to select the right community program to
      support.

PMID- 19601415
TI  - 2009: time sensitive healthcare issues await. SCHIP, Medicaid and Medicare
      payment reductions on lawmakers' to-do list for the new year.

PMID- 19601416
TI  - Managing your career in a difficult economy.

PMID- 19601417
TI  - Evaluating the board chair. Creating a process for assessing leaders reinforces a
      commitment to governance accountability and continuous improvement.

PMID- 19601418
TI  - The Triple Aim. Optimizing health, care and cost.

PMID- 19601419
TI  - Approaches to influencing physician behavior. Seek to be a servant leader when
      building partnerships with your physicians.

PMID- 19601420
TI  - Communication: working with remote teams.

PMID- 19601421
TI  - Management: is workplace conflict good?

PMID- 19601422
TI  - Modeling integrated fixed-film activated sludge and moving-bed biofilm reactor
      systems I: mathematical treatment and model development.
AB  - A mathematical model for integrated fixed-film activated sludge (IFAS) and moving
      bed biofilm reactor wastewater treatment processes was developed. The model is
      based on theoretical considerations that include simultaneous diffusion and Monod
      type reaction kinetics inside the biofilm, competition between aerobic
      autotrophic nitrifiers, non-methanol-degrading facultative heterotrophs, methanol
      degrading heterotrophs, slowly biodegradable chemical oxygen demand, and inert
      biomass for substrate (when appropriate) and space inside the biofilm; and
      biofilm and suspended biomass compartments, which compete for both the electron
      donor and electron acceptor. The model assumes identical reaction kinetics for
      bacteria within suspended biomass and biofilm. Analytical solutions to a 1
      dimensional biofilm (assuming both zero- and first-order kinetics) applied to
      describe substrate flux across the biofilm surface are integrated with a revised
      and expanded matrix similar to that presented as the International Water
      Association (London, United Kingdom) Activated Sludge Model Number 2d (ASM2d)
      stoichiometric and kinetic matrix. The steady-state mathematical model describes
      a continuous-flow stirred-tank reactor.

PMID- 19601423
TI  - Modeling integrated fixed-film activated sludge and moving-bed biofilm reactor
      systems II: evaluation.
AB  - A steady-state model presented by Boltz, Johnson, Daigger, and Sandino (2009)
      describing integrated fixed-film activated sludge (IFAS) and moving-bed biofilm
      reactor (MBBR) systems has been demonstrated to simulate, with reasonable
      accuracy, four wastewater treatment configurations with published operational
      data. Conditions simulated include combined carbon oxidation and nitrification
      (both IFAS and MBBR), tertiary nitrification MBBR, and post denitrification IFAS
      with methanol addition as the external carbon source. Simulation results
      illustrate that the IFAS/MBBR model is sufficiently accurate for describing
      ammonia-nitrogen reduction, nitrate/nitrite-nitrogen reduction and production,
      biofilm and suspended biomass distribution, and sludge production.

PMID- 19601424
TI  - Inhibition kinetics of phenolic compounds in aerobic degradation of organic
      wastewaters.
AB  - This study proposed a kinetic model for the aerobic degradation of high strength
      organic wastewaters with high concentrations of phenolic compounds. The model was
      based on the conventional Monod kinetic equation incorporating phenols'
      inhibition. Furthermore, a methodology for determining biokinetic constants was
      proposed. Olive-mill wastewater (OMWW) was used for the case study. The model and
      proposed methodology were fitted on the experimental data and it was proved that
      the aerobic degradation of OMWW was described satisfactorily. The following
      kinetic constants were determined: maximum specific substrate removal rate, 1.35
      h(-1); minimum microorganisms decay rate, 0.01 h(-1); inhibition coefficient of
      phenolic compounds, 373 mg L(-1); half-saturation concentration in carbon units,
      1004 mg L(-1); and decay acceleration coefficient of phenolic compounds, 231 mg
      L(-1). Finally, the biomass yield coefficient was found to be equal to 0.36.
      Thus, it was determined that the proposed methodology would be a useful tool for
      determining biokinetic constants of similar substrates.

PMID- 19601425
TI  - Catalytic ozonation for degradation of 2, 4, 6-trichloroanisole in drinking water
      in the presence of gamma-AlOOH.
AB  - Results show that catalytic ozonation with gamma-AlOOH can substantially enhance
      the removal effectiveness of 2, 4, 6-trichloroanisole (TCA) in drinking water.
      Scavenging of radicals tests reveals that the improved 2, 4, 6-trichloroanisole
      degradation is due to the enhanced generation of hydroxyl radicals. The uncharged
      surface hydroxyl groups on gamma-AlOOH in water can induce aqueous ozone
      decomposition to generate hydroxyl radicals. The catalytic activity of gamma
      AlOOH decreased as thermal treatment temperature increased.

PMID- 19601426
TI  - Adsorption of lead(II) from water by carbon nanotubes: equilibrium, kinetics, and
      thermodynamics.
AB  - Adsorption of lead(II) from water on carbon nanotubes (CNTs) was investigated
      using a series of batch adsorption experiments. The adsorption rate was studied
      experimentally at various temperatures, contact times, and initial pH and
      lead(II) concentrations. It was observed that a considerable amount of lead(II)
      was adsorbed during the first 5 minutes of contact time. The pH of the solution
      strongly influenced the amount of adsorption, and the best results were obtained
      when pH value was approximately 6. For the adsorption isotherm, the experimental
      data were analyzed by three two-parameter isotherms (Langmuir, Freundlich, and
      Temkin) and four three-parameter isotherms (Redhich-Peterson, Sips, Toth, and
      Khan). The three kinetic models used to test the experimental data were Lagergren
      first-order, second-order, and the Elovich equation. The results obtained from
      the study of the thermodynamic parameters showed that the adsorption of lead(II)
      onto CNTs was a spontaneous and endothermic process.

PMID- 19601428
TI  - Chromium fate in constructed wetlands treating tannery wastewaters.
AB  - Nine experimental wetlands were built to determine chromium partitioning inside
      systems treating tannery wastewaters. Results showed 5-day biochemical oxygen
      demand and chromium removals of 95 to 99% and 90 to 99%, respectively. The
      majority of chromium was found in association with media (96 to 98%), followed by
      effluents (2.9 to 3.9%), and the least was found in plant parts (0.1%). Chemical
      speciation modeling of solutions and scanning electron microscope analysis
      suggest two potential chromium removal mechanisms--sorption/coprecipitation with
      iron hydroxides or oxyhydroxides and biomass sorption. The release of the
      majority of chromium in the iron- and organic-bound phases during sequential
      extractions supports the proposed dominant removal mechanisms. The use of a
      mixture of peat and gravel resulted in lower removal efficiencies and stronger
      partitioning in organic phases during sequential extractions. Chromium was
      efficiently removed by wetlands, retained through chemical and biological
      processes. Future research will focus on further exploring removal mechanisms and
      proposing management strategies for the chromium-containing wetland media.

PMID- 19601427
TI  - Quantification of the inert chemical oxygen demand of raw wastewater and
      evaluation of soluble microbial product production in demo-scale upflow anaerobic
      sludge blanket reactors under different operational conditions.
AB  - This paper investigates the production of soluble microbial products (SMPs) in
      demonstration-scale upflow anaerobic sludge blanket reactors operated under
      different conditions and fed with raw wastewater. The results showed that 9.2 +/-
      1.3% of the influent soluble chemical oxygen demand (COD) could be considered
      inert to anaerobic treatment and that the amount of COD produced by biomass
      varied from 30 to 70 mg x L(-1), accounting for 45 to 63% of the soluble effluent
      COD. The accumulation of SMP appeared to be dependent on the hydraulic retention
      time (HRT) applied to the reactors, with a larger accumulation of SMP observed at
      the lowest HRT (5 hours); this may have been due to stress conditions caused by
      high upflow velocity (1.1 m x h(-1)). In terms of residual COD characterization,
      ultrafiltration results showed that higher amounts of high molecular weight
      compounds were found when HRT was the lowest (5 hours), and that the molecular
      weight distribution depended on the operational condition of the reactors.
      Biodegradability tests showed that the low and high molecular weight SMPs were
      only partially degraded anaerobically (10 to 60%) and that the high molecular
      weight SMPs were difficult to degrade aerobically.

PMID- 19601429
TI  - Identification and application of physical and chemical parameters to predict
      indicator bacterial concentration in a small Californian creek.
AB  - This study of Aliso Creek in California aimed to identify physical and chemical
      parameters that could be measured instantly to be used in a model to serve as
      surrogates for indicator bacterial concentrations during dry season flow. In this
      study, a new data smoothing technique and ranking/categorizing analysis was used
      to reduce variation to allow better delineation of the relationships between
      adopted variables and concentrations of indicator bacteria. The
      ranking/categorizing approach clarified overall trends between physico-chemical
      data and the indicators and suggested sources of the bacteria. This study also
      applied a principle component regression model to the data. Although the model
      was promising for predicting concentrations of total and fecal coliforms, it was
      somewhat weaker in predicting enteroccocci.

PMID- 19601430
TI  - Adsorptive removal of phenol from contaminated water and wastewater by activated
      carbon, almond, and walnut shells charcoal.
AB  - The adsorption process is gaining interest as an effective process for advanced
      water and wastewater treatment. Phenol, as a toxic material in industrial
      effluents, should be removed because of its environmental and health effects. The
      present study involves an investigation of the use of three carbonaceous
      materials--activated carbon laboratory-grade (ACL), almond shell charcoal (ASC),
      and walnut shell charcoal (WSC)--as adsorbents for the removal of phenol from
      aqueous solutions. For the first time, the adsorptive removal of phenol using ASC
      and WSC was investigated. Findings have been compared with (ACL) results. Batch
      experiments were carried out to obtain adsorption equilibrium isotherms with
      phenol-spiked synthetic solutions. The effects of adsorbent amounts, pHo, initial
      concentration, and contact time on the adsorption of phenol were studied. Maximum
      removals of phenol from contaminant water with ACL, ASC, and WSC were 99.87,
      91.36, and 78.17%, respectively, and from industrial wastewater were 99.71,
      85.54, and 65.49%, respectively.

PMID- 19601431
TI  - Poor KSF uptake to be focus of review.

PMID- 19601432
TI  - Has nursing been freed?

PMID- 19601433
TI  - Good communication helps to build a therapeutic relationship.

PMID- 19601434
TI  - Sitting and pressure ulcers. 1: Risk factors, self-repositioning and other
      interventions.
AB  - This is the first in a two-part unit on continuous unrelieved sitting and its
      role in pressure ulcer development. The unit highlights points from new Tissue
      Viability Society (2009) guidelines. This part examines risk factors and
      interventions involving self-repositioning in vulnerable patients.

PMID- 19601435
TI  - Exploring how the development of a nurse-led vascular access service has
      benefited patients.
AB  - The management and care of patients in Greater Glasgow and Clyde needing long
      term vascular access has changed markedly over the past six years. A nurse-led
      vascular access service has been introduced to reduce waiting times for patients
      requiring long-term venous access for treatments such as chemotherapy, long-term
      antibiotics, renal dialysis and feeding. Nurses in the service now insert
      tunnelled central venous catheters (TCVCs) and also educate and train other
      healthcare professionals. This service has led to a reduction in complications
      and provided a source of expert advice for both patients and healthcare
      professionals.

PMID- 19601436
TI  - Exploring patients' experiences of a community matron service using storybooks.
AB  - BACKGROUND: Several Department of Health policy documents outline a vision for
      services to be designed around patients. The community matron service was
      introduced across NHS South of Tyne and Wear PCTs in 2005 and has developed over
      the last four years to offer a seven-day service to patients, delivered by 52
      community matrons. METHOD: A project in 2008 to gather patients' views of the
      service led to the development of service 'storybooks'. These are a rich source
      of data, captured through in-depth, semi-structured interviews. RESULTS AND
      CONCLUSION: The data shows the service is well regarded and beneficial. The most
      important factors for patients included: an assurance of the service being there;
      reliable/supportive staff; effective communication skills; and matron
      availability. The storybooks reveal high levels of patient satisfaction and the
      importance the service gives to patient involvement.

PMID- 19601438
TI  - On how to design a leadership programme to boost quality.

PMID- 19601437
TI  - Productive Ward. 1: Implementing the initiative across a large university
      teaching hospital.
AB  - The first in a two-part series on how to implement the Productive Ward
      initiative, this article looks at its implementation across a large teaching
      hospital.

PMID- 19601439
TI  - Accuracy is the key element of a public health agenda.

PMID- 19601440
TI  - An opportunity to transform patients' lives.

PMID- 19601441
TI  - Promoting oral health care: more than just lip service.

PMID- 19601442
TI  - New drug information: Toviaz.

PMID- 19601443
TI  - A spreading, chronically itchy rash.

PMID- 19601444
TI  - A day in the life.

PMID- 19601445
TI  - How to perform a comprehensive examination of the knee.

PMID- 19601446
TI  - Sudden onset of substernal chest pain in a college student at rest.

PMID- 19601447
TI  - A role in trauma care for advanced practice clinicians.
AB  - Advanced practice clinicians (APCs) are increasingly being utilized to care for
      patients on trauma services, but the quality of care provided by these alternate
      delivery models has been questioned. We hypothesized that APCs could safely
      administer trauma care that had traditionally been provided by surgical
      residents. Outcomes from an APC trauma-care delivery model were compared with
      those reported in the National Trauma Data Bank (NTDB). Parameters included in
      the comparison were mechanism of injury (MOI), length of hospital stay (LOS),
      injury severity score (ISS), and mortality. When MOI was used as the basis of
      comparison, the percentage of patients treated at the trauma center and the
      percentage of patients with information in the NTDB were similar. Despite having
      more seriously injured patients, the APC-staffed trauma center demonstrated a
      shorter LOS for all ISS categories; comparisons of patients with ISS >24 did not
      reach statistical significance. In addition, the APC-staffed trauma center had a
      statistically lower overall combined mortality rate when categorized by ISS. We
      conclude that an APC trauma-care delivery model provides outcomes at least as
      good as those reported by the NTDB.

PMID- 19601448
TI  - Spinal cord astrocytomas: rare but life-threatening tumors in children.

PMID- 19601449
TI  - Erythema infectiosum: recognizing the many faces of fifth disease.

PMID- 19601450
TI  - A simple new blood test for allergy triggers.

PMID- 19601451
TI  - Is continuity of care a victim of progress?

PMID- 19601452
TI  - Unusual vascular structures in the chest cavity.

PMID- 19601453
TI  - Face to face: glimpsing the man behind the mask.

PMID- 19601454
TI  - A classic case of median rhomboid glossitis.

PMID- 19601455
TI  - [Laparoscopic training--the guarantee of a future in pediatric surgery].
AB  - Laparoscopy is considered today the highlight of modern surgery, the forerunner
      of the fascinating world of video and robotic surgery, both of them derived from
      the sophisticated areas of aeronautic industry. Remarkably, Romanian specialists
      keep up with the pace of worldwide technological developments, assimilating one
      by one each and every video endoscopic procedure. In the early 90s, the Romanian
      laparos-copic school was founded with the contribution of many important
      personalities; their activities and achievements have been an inspiration for the
      following generation of laparoscopic surgeons. In this last decade, the newest
      branch of laparoscopic surgery in our country, pediatric laparoscopy, managed to
      evolve from its "shy" beginnings to become an important method of improving the
      quality of surgical procedures, to the benefit of our "small patients". The
      purpose of this article is to encourage and promote minimally invasive video
      endoscopic surgery training, emphasizing its crucial role in the education and
      professional development of the next generation of pediatric surgeons, and not
      only. The modem concept of laparoscopic training includes experimental scientific
      practices, as well as the newest technical acquisitions such as virtual reality
      video-electronic simulation.

PMID- 19601456
TI  - [Anesthesia for experimental surgery in swine].
AB  - New surgical techniques cannot be safely and widely performed in human subjects
      unless they are first applied to large animal models. Experimental model using
      swine as surgical practice subject is one of the most reliable and widely
      practiced, taking into consideration the similarity between human and swine
      anatomy. Based on our large experience (around 100 pigs) we hereby present
      important aspects of handling and anesthesia procedures for pigs. Our goal is to
      share our experience with young surgical and anesthesia investigators who are
      planning investigations using pig as an experimental animal.

PMID- 19601457
TI  - MELD exceptions and new predictive score of death on long waiting lists for liver
      transplantation.
AB  - BACKGROUND: Cirrhosis related complications, considered MELD exceptions, proved
      to add prognostic value to the MELD score in predicting waiting list mortality.
      AIM: To identify the predictive value for death on a long waiting list (WL) for
      the complications of liver disease. METHODS: During 2004-2007, 372 consecutive
      adult patients were listed for liver transplantation (LT). To identify the
      potential predictors of patient death, univariate and multivariate Cox's
      proportional hazards regression model was used. RESULTS: In the univariate
      survival analysis the following variables were significant: spontaneous bacterial
      peritonitis, refractory ascites, hyponatremia, hepatic encephalopathy,
      hepatorenal syndrome, initial and current MELD score, initial and current Child
      Pugh score. The independent predictors of death on our WL were: refractory
      ascites (p=0.002) and hepatorenal syndrome (p=0.002). Based on a logistic
      regression analysis a new score has been developed: Score = 1/(1+ exp(-(-4.38 +
      1.34 x Refractory ascites + 0.9 x Hepatorenal syndrome + 0.15 x Current MELD).
      The c-statistic for the new score for prediction of death on the WL was 0.85
      compared to 0.80 for current MELD score. CONCLUSION: Refractory ascites and
      hepatorenal syndrome should add valuable points to the current MELD in order to
      better prioritize for LT patients included on long WL. ABBREVIATIONS: Liver
      transplantation (LT), Model for End-Stage Liver Disease (MELD), waiting list
      (WL), United Network for Organ Sharing (UNOS), standard deviation (SD), receiver
      operating characteristic (ROC), hepatitis B virus (HBV), hepatocellular carcinoma
      (HCC), positive predictive value (PPV), negative predictive value (NPV), Child
      Turcotte-Pugh (CTP), hepatic venous pressure gradient (HVPG).

PMID- 19601458
TI  - [Liver resection for benign hepatic lesion: mortality, morbidity and risk factors
      for postoperative complications].
AB  - The aim of this study was to evaluate the result of liver resection for benign
      hepatic lesion and to determine the risk factors for postoperative complication.
      Between January 2001 and December 2006 (6 years), a total of 50 patients with
      benign hepatic lesion underwent hepatic resection and were retrospectively
      reviewed. The sex ratio was M/F=31/19 with a mean age of 44 years (range 2-74).
      The diagnosis was: hydatid cyst in 24 patients (48%); hemangioma in 14 patients
      (28%), focal nodular hyperplasia (FNH) in 6 (12%), hepatic adenoma in 3 cases
      (6%), and hepatoblastoma in 3 patients (6%). Fourty patients (80%) had symptoms
      prior to surgery (mainly abdominal pain). The abnormalities were located in 34
      cases on the left liver (II-IV Couinaud segments) and in 16 cases on the right
      liver (V-VIII Couinaud segments). Twenty-nine patients (58%) underwent atypical
      resections, 4 underwent left hemihepatectomy (8%), 16 underwent left lobectomy
      (32%) and 1 patient was treated by segmentectomy (2%). Median operating time was
      108 minutes (range 60-220) and the median blood lost was 310 ml range (30- 1500).
      The morbidity rate was 18% (9 patients). Independent risk factors associated with
      the development of postoperative complication were intraoperative blood lost more
      than 1200 ml (p=0,015; OR=1,7) and the operating time more than 150 minutes
      (p=0,048; OR=1,09). There was no mortality. The mean postoperative
      hospitalization was 7,86 days with the range 3-23 days. CONCLUSION: 1. Liver
      resections for benign hepatic lesion performed in specialized centers are safe
      and efficient, with low morbidity and mortality. 2. Postoperative morbidity was
      related to the intraoperative blood lost more than 1200 ml and to the operating
      time more than 150 minutes.

PMID- 19601459
TI  - [Esophago-digestive anastomosis dehiscence].
AB  - This paper aim is to discuss the main etiopathogenic aspects responsible for eso
      digestive anastomotic leakage, as well as prophylactic and therapeutic measures
      of this postoperative complication. There were studied 173 consecutive eso
      digestive anastomosis: 103 anastomosis performed for malignancy and 70
      anastomosis for benign conditions. Surgical operations followed by an eso
      digestive anastomosis were: esophageal reconstruction for benign esophageal
      caustic strictures (n=67); total gastrectomy (n=55); total esophagectomy (n=13);
      total esophagectomy plus total gastrectomy (one case); eso-gastrectomies (n=34);
      upper gastric pole resection (n=2); distal esophageal resection (n=1). Eso
      digestive anastomosis topography were cervical (n=81), intrathoracic (n=37) and
      abdominal (n=57). There were 30 eso-gastrostomies, 81 eso-jejunostomies, and 62
      eso-colostomies. There were recorded 24 eso-digestive anastomotic dehiscences
      (13.8%): 14 in the cervical region (17.2% out of 81 cervical anastomosis); 5
      intrathoracic leakages (14.2% out of 35 anastomosis); 5 intraabdominal
      anastomotic dehiscences (8.7% out of 57 intraabdominal anastomosis). Four
      patients died as an anastomotic leakage consequence: two patients died after
      cervical eso-gastrostomy dehiscences, one patient died after an intrathoracic eso
      jejunostomy leakage, and one patient died after intraabdominal eso-gastrostomy
      leakage. In conclusion, we analyze postoperative results, emphasizing the role of
      discovering and removal of predisposing factors which may lead to an eso
      digestive anastomotic leakage.

PMID- 19601461
TI  - Electrosurgical loop excision/conisation for cervical intraepithelial neoplasia
      in an algorithm that excludes punch biopsy--a study of 210 cases.
AB  - This study aims to evaluate the use of LLETZ/conisation in an algorithm that
      excludes the colposcopically guided biopsy. MATERIAL AND METHODS: The study was
      carried out on 210 patients with LLETZ/conisation, performed in our service in 2
      years. They were selected by pap smear, colposcopy, HPV genotyping, without punch
      biopsy. RESULTS: The pathological results on the excision specimen showed: benign
      lesion 10%, CIN 1/condyloma 58%, CIN 2 18%, CIN 3/CIS 11%, microinvasion 2% and
      invasion 1%. The Pap test showed: HGSIL 27%, LGSIL 56%, ASCUS 13%, and
      normal/benign in 4%. The therapeutic efficiency of the excisional treatment
      showed that there was a 9.5% excessive treatment, 14.8 residual lesions, 3 cases
      of hemorrhage, 2 cervical stenosis, and 7 cases with specimen alteration that
      made the pathological diagnostic difficult or impossible. In conclusion, the
      LLETZ/conisation are ambulatory procedures with an acceptable rate of over
      treatment and residual lesions, and reduced rate of complication.

PMID- 19601460
TI  - Could serologic and ultrasonographic indexes be useful for therapeutic decisions
      in patients with ovarian cancer?
AB  - The objective of this study is to assess and quantify a relationship between
      different categories of prognostic factors in ovarian cancer, to establish
      patterns that explain the aggressiveness of some tumors, as well as to consider
      the above mentioned issues with regard to therapy decisions. MATERIAL AND
      METHODS: This prospective observational and analytical research comprised 124
      cases. The following were calculated: descriptive statistics, statistical
      comparisons, linear and multiple regressions, survival calculations, for
      clinical, serological, ultrasonographic, biological and temporal variables. In
      addition, new prognostic indexes were introduced. RESULTS: A significant
      difference was found between well known predictors for evolution of ovarian
      cancer in the malignant and benign groups: Platelet Derived Endothelial Cell
      Growth Factor (PDECGF) p=0.0001; CA125 p=0.0027. Potential ultrasonographic and
      serologic predictors for malignity of ovarian masses were identified. Only two
      ultrasonographic predictors: Multilocular Solid Masses insight the tumor and
      Diastolic Notch fulfilled the required values in order to be considered
      independent predictors for disease free interval. High level correlation between
      serologic and ultrasonographic predictors was calculated; significant correlation
      between preoperative and postoperative vascular indexes was demonstrated.
      DISCUSSIONS: The results suggest the possibility of therapy in ovarian cancer
      patients adjusted also to the angiogenic component of the disease.

PMID- 19601462
TI  - [Endoscopic surgery for benign rhino-sinusal tumors].
AB  - OBJECTIVES: Evaluation of the efficiency for endoscopical transnasal surgical
      techniques of rhino-sinusal benign tumors. MATERIAL AND METHOD: Retrospective
      study underwent between January 2005 - January 2006 in ENT&HNS Department "Sf.
      Maria" Bucharest, including 31 consecutive patients diagnosed with rhino-sinusal
      benign tumors. The patients underwent endoscopical surgical resections, with a
      follow-up period ranging between 14-26 months (average of 17,2 months). RESULTS:
      We present the results achieved during the study over a group of patients with
      benign tumors from which 14 cases were inverted papillomas (45,16%), 7 cases of
      haemangiomas (22,58%), 3 cases of neurofibromas, and 3 cases of juvenile
      angiofibromas (each representing 9,67%), 2 cases of ossifying fibromas, and 2
      cases of ameloblastomas (each representing 6,45%). The surgical procedures were
      performed under general anesthesia by the same surgeon. In the follow-up period,
      the patients were evaluated endoscopically and radiologicaly. The recurrence rate
      was 12,90% (4 cases) that required combined endoscopic and open approach: 2 cases
      of inverted papillomas and 2 cases of ossifying fibromas. CONCLUSIONS: Endoscopic
      transnasal approach of benign rhino-sinusal tumors is a successful surgical
      method, with the advantage of no esthetics impairments, reduced hospitalization,
      and preservation of the patient's quality of life, with medium and long term
      results comparable with open surgery.

PMID- 19601463
TI  - [The pig model for the laparoscopic antireflux surgery training].
AB  - The laparoscopic treatment of the Gastroesophageal Reflux Disease (GERD) includes
      antireflux surgery (AR) procedure which may be performed in an optimal functional
      manner. To achieve this target adequate training is mandatory for the surgical
      team. In the "Sf. John" Laparoscopic Training Center (Bucharest, Romania) we have
      studied the advantages and disadvantages of a pig model for training in
      laparoscopic antireflux surgery. 16 pigs (20-25 kg) were included in this study.
      The results of this study included: 1. a complete description of the laparoscopic
      Nissen fundoplication in pigs and 2. the evaluation of the pig model for
      laparoscopic AR surgery. The use of pigs with anesthesia as a training model for
      laparoscopic AR surgery present certain advantages for the trainees: clear and
      humans similar anatomy, real surgical conditions (OR, equipment, instruments,
      lived animals).

PMID- 19601464
TI  - [Clinical and therapeutical considerations regarding odontogenic acute
      mediastinitis].
AB  - Odontogenic acute mediastinitis is an polymicrobial infections caused in most
      cases by gram negative and anaerobic germs. The odontogenic origin of the cases
      in this study was based on anamnestic inquiry of the patients, which reveales a
      dental treatment 7-15 days before the diagnosis of acute mediastinitis was
      established. Clinical features are often nonspecific at the debut of this
      affection; septic shock could appear suddenly associated with multiple systems
      and organs failure. This is the explication why, some of these patients presented
      septic shock when are diagnosed. In this situations, when acute mediastinitis is
      suspected, based on clinical and imaging findings, it must be confirmed by
      surgical exploration and perioperative bacteriological evaluations. Positive
      diagnosis is based on clinical features associated with labs and imaging studies.
      Surgery plays an important role in therapy of acute mediastinitis: debridement
      and drainage of mediastinum with subsequently lavage of it, using antiseptic
      solutions. Broad spectrum antibiotherapy should be administrated immediately,
      before antibiogram is ready.

PMID- 19601465
TI  - [Pleurotomy--an operation by the general surgeon].
AB  - The authors present the newest data of a minimal thoracic technique: the
      pleurotomy. In our times this technique requires the modem chest tubes, the
      complete pleurotomy sets for different emergent situations. The authors presents
      the indications, the possible complications, their own technique of pleurotomy
      and the actual management of pleural drainage.

PMID- 19601466
TI  - [I. Left-sided appendicitis and immobile uterine retroversion. 1931].

PMID- 19601467
TI  - [II. Left-sided appendicitis. 1937].

PMID- 19601468
TI  - [Voluminous complicated epigastric hernia].
AB  - Epigastric hernia, apparently minor injury, neglected can reach impressive sizes,
      with major un-esthetic effect. In an unfavorable clinically context (morbid
      obesity, chronic respiratory failure, ground cancer, diabetes, heart failure)
      complications occur (incarceration, strangulation) with a complex picture. We
      present three clinical observations, including a low occlusion by fixed
      transverse colon necrosis in a strangulated epigastric hernia with pyo-stercoral
      phlegmon.

PMID- 19601469
TI  - Laparoscopic repair of post-traumatic diaphragmatic hernia: a case report.
AB  - In a large number of cases, post-traumatic diaphragmatic hernias (PTDH) are a
      consequence of occult diaphragmatic injuries associated with penetrating
      abdominal trauma. We present a case of a 26-year-old male patient who, 2 months
      prior to the current admission, sustained a non-penetrating stab wound to the
      left anterior chest below the nipple. Upon presentation the patient complained of
      epigastric pain radiated to the left shoulder, and nausea and vomiting. The chest
      X-ray, and abdominal and thoracic CT scan were inconclusive. The patient was
      sutured and discharged. The laparoscopic approach was selected as a diagnostic
      and minimally invasive therapeutic method. The suspected diagnosis of PTDH was
      confirmed. The herniated organs (transverse colon, small bowel loops, and greater
      omentum) were reduced, and the diaphragmatic defect was sutured by placing 3 non
      resorbable 2.0 knots. The suture was reinforced with a composite mesh affixed
      with resorbable clips. Postoperative period was uneventful, and the patient was
      discharged 4 days later.

PMID- 19601470
TI  - [Complications in morbid obesity treatment--pylorus obstruction caused by a
      deflated intragastric balloon].
AB  - An aggressive array of new treatments and improvements of existing approaches for
      addressing morbid obesity were developed during the last two decades in response
      to the recognition that a new pandemic affects humanity, i.e. obesity. Initially
      used as a temporizing solution for other specific interventions used for obesity
      treatment, the endoscopic placement of an intragastric balloons has currently
      became in certain cases a complete therapeutic solution. Multiple studies
      emphasize the efficiency of this new therapeutic method, in some cases resulting
      in a 45 kg weight loss at the end of the monitoring period. The intragastric
      balloon, after endoscopic placement can be kept into position for an average
      period of 4-6 months. After this period, balloon extraction is recommended
      because of the complications that can occur with prolonged intragastric
      placement. This paper presents a case of pyloric obstruction by an intragastric
      balloon kept for 14 months. In this case, the initial approach was endoscopic,
      but the surgical approach offered the definitive therapeutic solution.

PMID- 19601473
TI  - Granular cell tumor of the penis shaft: case report and literature review.
AB  - INTRODUCTION: Granular cell tumors (GCT) are uncommon soft tissue neoplasms of
      presumed neural origin that rarely involve the male external genitalia. Penile
      lesions are distinctly uncommon with less than 20 cases reported till now.
      OBJECTIVE: In the present paper we describe the clinicopathological and
      immunohistochemical findings in a case of GCT of the penis shaft in a 31-years
      old man. RESULTS AND CONCLUSIONS: On physical examination the patient was found
      to have a small ovoid mass, 20 x 10 mm in diameter, at the left postero-lateral
      area of the penis' base. The mass was firm on palpation with no fixation on the
      neighboring tissues. The lesion was completely excised under loco-regional
      anesthesia. The surgical specimen was an ovoid, gray-white, elastic mass, of 10 x
      5 mm. Microscopically, the tumor was moderately cellular and was composed of
      polygonal-shaped cells with abundant granular eosinophilic cytoplasm. Tumor cells
      were disposed in nests, cords, and trabeculae and showed perineural invasion. The
      tumor presented bland cytological features with only focal slight nucleo-megaly.
      Mitotic activity was undetectable. The tumor cells showed diffuse
      immunohistochemical expression for S100 protein. At 6 month after surgery the
      patient was free of persistent/recurrent disease or metastatic spread of the
      tumor. We discuss the clinical, histo-immunohistochemical and therapeutical
      features of this unusual penile tumor, the single one encountered in the
      Department of Pathology from Timisoara County Hospital and, to our knowledge, the
      only one reported in the Romanian medical literature.

PMID- 19601472
TI  - Atypical ductal adenocarcinoma of the prostate with endometrioid
      immunohistological features.
AB  - We present the case of a 52-year-old Caucasian male, admitted to our institution
      for a verumontanum adenocarcinoma, partially resected endoscopically, a month
      earlier at another urological clinic. The prior pathological examination wasn't
      able to give diagnosis. The extensive assessment by clinical workup, ultrasound,
      flexible cystoscopy, CT scan, and MRI revealed a prostatic tumor extending from
      the verumontanum to the left lobe and seminal vesicle. The patient underwent
      radical prostatectomy. The pathological examination revealed a ductal like
      adenocarcinoma, positive on immunohistochemistry for pan cytokeratin (AE1/AE3),
      CD10, endomysial antibody EMA and progesterone receptors (PR) and negative for
      prostate specific antibody (PSA), prostatic specific acid phosphatase (PSAP) and
      androgen receptors (AR). Ductal like adenocarcinoma of the prostate with
      endometrioid immunohistological features in the absence of prostate markers is an
      unusual condition.

PMID- 19601471
TI  - [Right atrial thrombosis with acute abdominal onset].
AB  - Intracardiac masses are detected more frequently due to the availability of
      echocardiography. Right atrial thrombosis is rare comparatively with that of the
      left atrium. The clinical presentation of the patient with right atrial
      thrombosis is linked with a misleading association between cardiovascular signs
      and digestive signs (acute abdominal pain, vomiting and marmorated skin of
      flanks). Initial clinical suspicions of acute pancreatitis, entero-mesenteric
      infarction and complicated gastro-duodenal ulcer were invalidated by imagistic
      investigations -- echocardiography and CT. The massive thrombus located in the
      right atrium, prolapsing during diastole through the tricuspid valve, was
      associated with the increase in plasmatic D-dimers and new ECG modifications type
      right bundle block (hemodynamic straining of the right ventricle). The evolution
      was favorable, after heparin-therapy by infusing pump, with relief of
      cardiovascular and digestive symptoms after the first 6 hours; after 36 h from
      the beginning of the treatment the thrombus was lysed. Sudden death likelihood
      through complete obstruction of the tricuspid ostium was prevented due to the
      early diagnosis offered by imagistic methods.

PMID- 19601474
TI  - [Difficulties in diagnosis and surgical treatment of a giant retroperitoneal
      lipoma].
AB  - Primary retroperitoneal tumors are relatively rare and the histological
      characters vary. We present the case of a retroperitoneal lipoma in a 51-year-old
      male patient, whose main complain was enlarging of the abdomen in the last 2
      months. The CT of the abdomen and pelvis revealed a giant retroperitoneal tumor.
      The patient suffered a surgical intervention that revealed a giant
      retroperitoneal tumor, 40/35 cm, weighting 14 Kg. The pathology exam established
      the diagnosis: retroperitoneal lipoma with areas of necrosis and
      lipogranulomatosis. The postoperative evolution was simple.

PMID- 19601475
TI  - Integrating health promotion into national health policy.

PMID- 19601476
TI  - Looking at research consent forms through a participant-centered lens: the PRISM
      readability toolkit.
AB  - Communicating in lay language is an underdeveloped skill among many researchers-a
      limitation that contributes to low readability among research consent forms and
      may hinder participant understanding of study procedures and risks. We present
      the Project to Review and Improve Study Materials (PRISM) and its centerpiece,
      the PRISM Readability Toolkit. The toolkit provides strategies for creating study
      materials that are readable and participant centered, focusing on consent forms
      but also addressing other participant materials. Based on plain language
      principles, this free resource includes a flexible menu of tools, such as an
      editing checklist, before and after examples, easy-to-read template language, and
      a list of alternative words. Among PRISM's ongoing goals is to test the toolkit
      with populations groups.

PMID- 19601477
TI  - Connecting children to recreational activities: results of a cluster randomized
      trial.
AB  - PURPOSE: Identify if outreach support increases school-aged children's
      participation in recreational activities. DESIGN: Cluster randomized trial.
      SETTING: Sixteen schools in economically vulnerable neighborhoods were randomized
      to either an intervention or control group. SUBJECTS: Children in grades 3 to 5
      and their families were invited to participate. INTERVENTION: Children in
      intervention schools were assigned a "connector" (outreach worker) to facilitate
      participation in recreation activities. MEASURES: The Children's Assessment of
      Participation and Enjoyment (CAPE) was the primary measure at baseline, middle,
      and end of 1 year. Demographics, body mass index, child physical and psychosocial
      health, coordination, and self-esteem were measured. ANALYSIS: A generalized
      linear model was used to test differences between intervention and control
      groups. RESULTS: Three hundred and sixty children enrolled, and 306 (85%)
      completed the study. A greater proportion of children in the intervention group
      compared with the control group increased participation in physical activity (21%
      vs. 10%, p = .02). Children who increased their activity were more likely to have
      higher levels of contact with the connectors (31% vs. 8%, p = .001). Study
      limitations included (1) 29% of eligible families participated, (2) first use of
      the CAPE instrument as a longitudinal measure, and (3) connectors were not
      blinded to group assignment. CONCLUSION: Children living in vulnerable
      neighborhoods benefit from outreach workers to connect them with physical
      activity programs.

PMID- 19601478
TI  - Physical activity patterns of American Indian and Alaskan Native people living in
      Alaska and the Southwestern United States.
AB  - PURPOSE: Assessment of self-reported physical activity (PA) and effects on health
      measures. DESIGN: Cross-sectional analysis of baseline data from a cohort study.
      SETTING: Education and Research Towards Health study participants from Alaska and
      the Southwestern United States enrolled from 2004 to 2007. SUBJECTS: Total of
      10,372 American Indian and Alaskan Native people (AI/AN) of at least 18 years.
      MEASURES: Participants completed computer-assisted, self-administered
      questionnaires, and anthropometric and health measurements were taken of each
      participant. ANALYSIS: Analysis of variance, chi2 tests, and multiple linear
      regressions were used. RESULTS: Almost 23% of participants reported less than 30
      minutes per week of moderate or vigorous activities. Half (49%) reported no
      vigorous activities. Characteristics associated with more time spent performing
      vigorous activity were male gender, age less than 40 years, higher income and
      education levels, and living in a rural area. Almost 70% of Alaskan participants
      and 36% of Southwest participants engaged in wild food-harvesting activities.
      Participants with higher levels of activity had significantly better clinical
      characteristics (high-density lipoprotein cholesterol, triglycerides, body mass
      index, and waist circumference). CONCLUSION: AI/AN people engage in many
      different physical activities, including traditional harvesting activities. Women
      had lower levels of PA than men, and participation in vigorous PA was associated
      with better clinical characteristics. These data can be used to guide health
      promotion efforts in AI/AN populations.

PMID- 19601480
TI  - Encouraging young Western Australians to be smarter than smoking.
AB  - PURPOSE: Smarter than Smoking is a multistrategy statewide youth smoking
      intervention. This article describes key strategies and results from its
      inception in 1995 to 2005. DESIGN: Comprehensive evaluation included formative
      research and baseline and follow-up surveys. Triennial national surveys provided
      independent monitoring of adolescent smoking prevalence. SETTING: Western
      Australia. SUBJECTS: 10- to 15-year-olds. INTERVENTION: A multipronged strategy
      mix, including mass media, the Internet, sponsorship, school initiatives,
      publications, and advocacy. MEASURES: Smoking prevalence, media awareness, and
      attitudes toward smoking and campaign messages. ANALYSIS: Trend comparisons
      across the first decade of the project, along with descriptive statistics.
      RESULTS: Significant attitudinal and behavioral shifts were observed following
      media waves and over time. There was a steady increase in the proportion who had
      never smoked (from 40% in 1996 to 61% in 2005). Results also showed a significant
      decrease in smoking prevalence from 1996 to 2005, down from 28% to 7% among 14
      year-olds and from 43% to 14% among 15-year-olds. CONCLUSIONS: Smarter than
      Smoking was effective in achieving positive shifts in awareness, attitudes,
      intentions, and behavior. Effectiveness appeared to have been enhanced by
      sustained long-term funding, youth involvement in strategy development, and a
      strong research and evaluation base.

PMID- 19601479
TI  - The Animadora Project: identifying factors related to the promotion of physical
      activity among Mexican Americans with diabetes.
AB  - PURPOSE: There is a dearth of information about factors related to physical
      activity among Mexican-Americans with diabetes. Self-efficacy and social support
      are associated with physical activity; however, little is known about their roles
      within different cultural groups. DESIGN: Focus groups were used to identify
      factors that motivated walking. SETTING: Two Mexican-American communities located
      in Tucson, Arizona. SUBJECTS: Individuals who attended diabetes education.
      INTERVENTION: A community-based provider organized walking groups with people who
      previously attended diabetes classes. Walkers participated in focus groups
      exploring themes related to their experiences. MEASURES: Self-efficacy, social
      support, and collective efficacy. Grounded theory was used to analyze focus group
      results using two rounds of analysis; the first identified references to self
      efficacy and social support, and the second added collective efficacy as a
      theoretic basis for walking. RESULTS: Among 43 eligible participants, 20
      participated in focus groups. Social support was expressed as commitment and
      companionship. Walkers demonstrated a high level of self-efficacy for walking.
      Development of group identity/social cohesion was also a motivator to walk.
      Collective efficacy emerged as an applicable theoretic model encompassing these
      themes and their interrelationship. CONCLUSION: Collective efficacy, or the
      belief that the group can improve their lives through collective effort, is a
      viable theoretic construct in the development of physical activity interventions
      targeting Mexican-Americans with diabetes.

PMID- 19601481
TI  - Potential health benefits and medical cost savings from calorie, sodium, and
      saturated fat reductions in the American diet.
AB  - PURPOSE: Model the potential national health benefits and medical savings from
      reduced daily intake of calories, sodium, and saturated fat among the U.S. adult
      population. DESIGN: Simulation based on secondary data analysis; quantitative
      research. Measures include the prevalence of overweight/obesity, uncontrolled
      hypertension, elevated cholesterol, and related chronic conditions under various
      hypothetical dietary changes. SETTING: United States. SUBJECTS: Two hundred
      twenty-four million adults. MEASURES: Findings come from a Nutrition Impact Model
      that combines information from national surveys, peer-reviewed studies, and
      government reports. ANALYSIS: The simulation model predicts disease prevalence
      and medical expenditures under hypothetical dietary change scenarios. RESULTS: We
      estimate that permanent 100-kcal reductions in daily intake would eliminate
      approximately 71.2 million cases of overweight/obesity and save $58 billion
      annually. Long-term sodium intake reductions of 400 mg/d in those with
      uncontrolled hypertension would eliminate about 1.5 million cases, saving $2.3
      billion annually. Decreasing 5 g/d of saturated fat intake in those with elevated
      cholesterol would eliminate 3.9 million cases, saving $2.0 billion annually.
      CONCLUSIONS: Modest to aggressive changes in diet can improve health and reduce
      annual national medical expenditures by $60 billion to $120 billion. One use of
      the model is to estimate the impact of dietary change related to setting public
      health priorities for dietary guidance. The findings here argue that emphasis on
      reduction in caloric intake should be the highest priority.

PMID- 19601482
TI  - Predicted national productivity implications of calorie and sodium reductions in
      the American diet.
AB  - PURPOSE: To model the potential long-term national productivity benefits from
      reduced daily intake of calories and sodium. DESIGN: Simulation based on
      secondary data analysis; quantitative research. Measures include absenteeism,
      presenteeism, disability, and premature mortality under various hypothetical
      dietary changes. SETTING: United States. SUBJECTS: Two hundred twenty-five
      million adults. MEASURES: Findings come from a Nutrition Impact Model that
      combines information from national surveys, peer-reviewed studies, and government
      reports. ANALYSIS: We compare current estimates of national productivity loss
      associated with overweight, obesity, and hypertension to estimates for
      hypothetical scenarios in which national prevalence of these risk factors is
      lower. Using the simulation model, we illustrate how modest dietary change can
      achieve lower national prevalence of excess weight and hypertension. RESULTS: We
      estimate that permanent 100-kcal reductions in daily intake among the
      overweight/obese would eliminate approximately 71.2 million cases of
      overweight/obesity. In the long term, this could increase national productivity
      by $45.7 billion annually. Long-term sodium reductions of 400 mg in those with
      uncontrolled hypertension would eliminate about 1.5 million cases, potentially
      increasing productivity by $2.5 billion annually. More aggressive diet changes of
      500 kcal and 1100 mg of sodium reductions yield potential productivity benefits
      of $133.3 and $5.8 billion, respectively. CONCLUSIONS: The potential long-term
      benefit of reduced calories and sodium, combining medical cost savings with
      productivity increases, ranges from $108.5 billion for moderate reductions to
      $255.6 billion for aggressive reductions. These findings help inform public
      health policy and the business case for improving diet. (AmJ Health Promot
      2009;23[6]:423-430.)

PMID- 19601483
TI  - Adapting physical activity interventions to prevent obesity in culturally diverse
      populations.

PMID- 19601484
TI  - Physical activity and health equity: evolving the science.

PMID- 19601486
TI  - Systematic review of interventions to increase physical activity and physical
      fitness in African-Americans.
AB  - OBJECTIVE: To identify characteristics of effective interventions designed to
      increase physical activity (PA) or fitness among African-Americans. DATA SOURCES:
      Articles published between 1985 and 2006. STUDY INCLUSION CRITERIA: Studies
      reporting PA or fitness change data in African-American participants were
      included. DATA EXTRACTION: Information on study design, intervention, data
      collection methods, and outcomes was extracted using a standardized form. DATA
      SYNTHESIS: Studies were ranked on quality and were summarized separately for
      adults and children. RESULTS: We identified 29 studies in adults and 14 studies
      in children. Most were randomized controlled trials. All but six specifically
      targeted African-Americans; comparisons of effectiveness in African-Americans vs.
      others were not possible. Methodological heterogeneity limited comparisons of
      findings across studies. In adults, most studies showed significant within-group
      pre-post improvements in PA, but only 10 studies found differences between
      intervention and comparison groups. Most studies in children were null.
      CONCLUSIONS: Effective programs in adults were from randomized controlled trials
      and involved structured exercise programs. Studies with explicit cultural
      adaptations did not necessarily result in better PA outcomes. Additional studies
      are needed with larger sample sizes, longer follow-up, attention controls,
      strategies informed by proven behavior change theories, and objective PA
      assessment.

PMID- 19601485
TI  - Systematic review of physical activity interventions implemented with American
      Indian and Alaska Native populations in the United States and Canada.
AB  - OBJECTIVE: To describe physical activity (PA) interventions implemented in
      American Indian/Alaska Native (AI/AN) populations in the United States and
      Canada. DATA SOURCES: MEDLINE, PubMed, ERIC, and Sociological Abstracts were used
      to identify peer-reviewed journal articles. Dissertation abstracts, Web sites,
      and conference proceedings were searched to identify descriptions within the gray
      literature from 1986 to 2006. STUDY INCLUSION AND EXCLUSION CRITERIA: The target
      population had to be described as AI/ AN, aboriginal, native Hawaiian, and/or
      native U.S. Samoan. PA interventions among indigenous populations of Latin
      America were not included. DATA EXTRACTION: Descriptions of 64 different AI/AN PA
      interventions (28 peer-reviewed journal articles and 36 in the gray literature)
      were identified. DATA SYNTHESIS: Data were synthesized by geographic region,
      intervention strategy, target audience, activities, and sustainability. RESULTS:
      Most interventions were conducted in the southwest United States (35.4%), in
      reservation communities (72%), and among participants 18 years and younger
      (57.8%). Forty-one percent of the 27 interventions with evaluation components
      reported significant changes in health, behavior, or knowledge. CONCLUSIONS:
      Effective AI/AN PA interventions demonstrated impact on individual health and
      community resources. Program sustainability was linked to locally trained
      personnel, local leadership, and stable funding. Culturally acceptable and
      scientifically sound evaluation methods that can be implemented by local
      personnel are needed to assess the health and social impact of many long-running
      AI/AN PA interventions.

PMID- 19601488
TI  - Closing thoughts. Field of health promotion.

PMID- 19601487
TI  - Proactive health consumerism: an important new tool for worksite health
      promotion.
AB  - Consumerism in health care has taken on the form of a major innovation among
      employers and health plans. Yet many of our efforts to enhance the skills and
      attitudes that enable consumerism have met with limited success. Proactive Health
      Consumerism is proposed as an approach that utilizes many of the hard-won lessons
      from health promotion research. Along with prerequisites that create the
      motivation and framework for increased health consumerism, this article provides
      a theory-driven example of a new tool for health promotion professionals to
      employ when enhancing the health consumer skills of working populations.
      Strategies for maximization of effectiveness and integration with supporting
      resources are also described.

PMID- 19601489
TI  - The issue of corrosion in dental implants: a review.
AB  - Pure titanium or titanium alloys, and to a lesser extent, zirconium, are metals
      that are often used in direct contact with host tissues. These metallic
      biomaterials are highly reactive, and on exposure to fluid media or air, quickly
      develop a layer of titanium dioxide (TiO2) or zirconium dioxide (ZrO2). This
      layer of dioxide forms a boundary at the interface between the biological medium
      and the metal structure, determining the degree of biocompatibility and the
      biological response of the implant. Corrosion is the deterioration a metal
      undergoes as a result of the surrounding medium (electrochemical attack), which
      causes the release of ions into the microenvironment. No metal or alloy is
      entirely inert in vivo. Corrosion phenomena at the interlace are particularly
      important in the evolution of both dental and orthopedic implants and one of the
      possible causes of implant failure after initial success. This paper comprises a
      review of literature and presents results of our laboratory experiments related
      to the study of corrosion, with special emphasis on dental implants. In situ
      degradation of a metallic implant is undesirable because it alters the structural
      integrity of the implant. The issue of corrosion is not limited to a local
      problem because the particles pmduced as a result could migrate to distant sites,
      whose evolution would require further studies.

PMID- 19601490
TI  - Effect of chewing gums on the production of volatile sulfur compounds (VSC) in
      vivo.
AB  - The aim of the present study was to evaluate the effect of two chewing gums on
      the production of volatile sulfur-containing compounds (VSC) in vivo. Fourteen
      periodontally healthy participants (20-35 years old) were included in the test
      panel. Test gum 1 (TG1) contained sucrose and Test gum 2 (TG2) contained xylitol
      and zinc citrate. Two series of tests were conducted with a double-blind cross
      over design. Following an overnight refrain from oral hygiene, VSC was measured
      before and at 5, 15, 30, 45 and 60 minutes of chewing the test gums. In the
      second series, VSC production was monitored prior to and up to 30 minutes after a
      rinse with cysteine 6 mM alone or after a rinse followed by chewing the test
      gums. For the first test, the results were analyzed by repeated measurements
      ANOVA for intra-group and paired sample t test for intergroup comparisons. In the
      second series, percent reduction of VSC was compared by Friedman and Wilcoxon
      tests (p < .05). The test gums did not differ in terms of VSC production, with
      values ranging from 146 ppb after 5 minutes to 86 ppb after 60 minutes. Similar
      reductions in VSC production following cysteine were observed for both test gums,
      with the largest reductions (71% to 52%) observed after 5 and 15 minutes. It can
      be concluded that VSC production is diminished after chewing gum and that the use
      of chewing gums reduces temporarily the VSC production enhanced by cysteine
      rinses.

PMID- 19601491
TI  - Frequency and distribution of Mutans Streptococci in dental plaque from caries
      free and caries-affected Venezuelan children.
AB  - Mutans Streptococci, in particular S. mutans and S. sobrinus, are generally
      considered to be the prime etiological bacteria of human dental caries. The aim
      of this study was to determine the frequency of mutans streptococci in dental
      plaque in three groups of caries-free and caries-affected Venezuelan children
      aged 2-6, 7-12, 13-19 years, and their possible association with dental caries.
      The frequency of mutans streptococci was determined in samples of pooled dental
      plaque collected from all detectable sources of 30 (62.5%) caries-affected and 18
      (37.5%) caries-free children. The samples were collected from all available tooth
      sites using a Hollenbak probe and immediately suspended in Ringer's solution,
      serially diluted and cultured in Mitis Salivarius (MS) agar for total
      streptococci determination and Mitis Salivarius Bacitracin (MSB) for isolation of
      mutans streptococci. The bacterial identification procedure was done using the
      API Rapid Strep System. The criteria used to determine dmft and DMFT was
      established by Klein and Palmer (1941). Mean dmft and DMFT were 6.4 +/- 3.2 and
      4.4 +/- 2.9, respectively. Ten (33%) out of 30 caries-affected children harbored
      mutans streptococci. The species most frequently found were S. mutans (20%), S.
      sobrinus (10%) and S. rattus (3.3%). Meanwhile, in the caries-free group only 6
      out of 18 children (33%) harbored mutans streptococci, specifically S. mutans and
      S. sobrinus, both at 17%, with no significant difference between the two groups.
      These results indicate that the percentage of children that harbored mutans
      streptococci was similar in both groups, suggesting that other acidogenic species
      may be responsible for caries development.

PMID- 19601492
TI  - Clinical evaluation of the use of three anesthetics in endodontics.
AB  - This study compared three anesthetics widely used in endodontics and analyzed the
      following variables: amount necessary to achieve adequate anesthesia; anesthetic
      efficacy, defined as no sensation during endodontic treatment; anesthetic
      duration; and cost-benefit. Sixty patients diagnosed with irreversible pulpitis
      of a mandibular molar were selected at the Dental Emergency Center of
      Universidade de Fortaleza, Brazil. Patients were randomly divided into three
      groups of 20 and were administered one of three anesthetic solutions for
      conventional regional block: 2% lidocaine with 1:2500 phenylephrine; 2%
      mepivacaine with 1:100,000 adrenaline and 4% articaine with 1:100,000
      epinephrine. The following variables were studied: number of cartridges necessary
      to obtain anesthetic success; anesthetic efficacy, defined as no sensation during
      endodontic procedures; anesthetic duration; cost-benefit ratio for each
      anesthetic. Mean number of cartridges necessary to obtain anesthetic success was
      2.76, and there was no statistically significant difference between the
      anesthetics used. Lidocaine had the best cost-benefit ratio. All anesthetics used
      were clinically efficient and had equivalent results for endodontic treatment.

PMID- 19601493
TI  - Effect of storage temperature on pH of in-office and at-home dental bleaching
      agents.
AB  - The aim of this study was to determine the pH of several commercially available
      in-office and at-home dental bleaching products stored at room temperature and
      refrigerated. The products were divided into in-office (n=09) and at-home (n=12)
      bleaching gels and submitted to two different temperatures, namely, room
      temperature (23 degrees C +/- 1 degree C) and refrigeration temperature (4
      degrees C +/- 1 degree C). The pH was measured using a portable pH meter with a
      direct electrode, which was calibrated with standard buffer solutions at pH 4.0
      and 7.0 and recalibrated for each new product. The pH of the dental bleaching
      products tested ranged from 2.39 +/- 0.10 to 6.52 +/- 0.09, and was found to vary
      significantly both with temperature and between bleaching agents. Most of the
      bleaching gels were found to be acidic, especially the in-office bleaching
      products, and the refrigerated at-home gels had the highest pH values. Thus, we
      conclude that the storage temperature affected the pH of the products tested.

PMID- 19601494
TI  - Influence of nutritional state on radiographic variables in upper canine teeth.
AB  - Permanent upper canine tooth impaction is related to both genetic causes and
      nutritional and local causes. Based on radiographic studies of children,
      Haavikko, 1974, calculated the median of the degree of calcification for each
      tooth according to age. The aim of our study was to establish associations
      between certain radiographic variables with respect to upper canine tooth buds
      and nutritional state in a population of schoolchildren. Thirty-three children of
      chronological ages 3 to 9 years from a population of rural schoolchildren took
      part in the study. The children were classified into three groups: malnourished,
      control and overweight. For the radiographic study we used a systematized
      technique using DSJ 70 kV radiographic equipment with 8 mA and Insight intraoral
      film (E F speed; Eastman Kodak, Rochester, NY). The images obtained from the 66
      radiographic studies were scanned. The program Image tool for Windows was used to
      measure: (a) distance from the canine cusp to the intermaxillary suture, (b)
      outer angle formed between the aris of the canine tooth and the plane that cuts
      the intermaxillary suture perpendicularly, (c) degree of calcification (d)
      presence of supernumerary teeth. The values of these variables were analyzed
      statistically with the Kruskal-Wallis test of the SPSS program. The results were:
      (a) For the distance variable there is no significant difference between the
      malnourished and control groups (p > 0.05), although there are differences (p <
      0.001) between the control and overweight groups; (b) There is no significant
      difference between nutritional states for the angle variable; (c) For the ratio
      between chronological age and dental age calculated according to degree of
      calcification, significant differences were found between the malnourished and
      overweight groups (p < 0.01), while the control group showed no difference
      regarding Haavikko's values (p > 0.05). Both the distance of the canine tooth bud
      and its degree of calcification vary in patients with nutritional disorders,
      therefore it would be useful to conduct a radiographic study at school age to
      detect tooth anomalies and reduce their consequences.

PMID- 19601495
TI  - Influence of desensitizing agents on the microshear bond strength of adhesive
      systems to dentin.
AB  - The aim of this study was to evaluate the effect of desensitizing agents on the
      micro-shear bond strength of adhesive systems to dentin. Forty bovine teeth were
      divided into 8 groups (n=5): G1--Single Bond (SB); G2--GH.F + SB; G3--
      Desensibilize + SB; G4--essensiv + SB; G5 --ingle Bond 2 (SB2); G6--H.E + SB2; G7
      -esensibilize + SB2; G8--Dessensiv + SB2. In all of the groups, the desensitizing
      agents were applied after phosphoric acid etching and before the dentin adhesive
      application. Z250 composite resin tubes were bonded on the treated surface. After
      24 hours, the teeth were tested in a universal machine. Data were submitted to
      ANOVA and Tukey's test (5%). The results showed that the groups where
      Desensibilize and Dessensiv were applied exhibited smaller bond strength values.

PMID- 19601496
TI  - Comparative study of the microtensile bond strength of three different total etch
      adhesives with different solvents to wet and dry dentin (in vitro test).
AB  - The aim of this study was to compare the microtensile bond strength of three
      different total etch adhesives: XP Bond (Caulk-Dentsply) versus Excite
      (Ivoclar/Vivadent) and Prime & Bond NT (Caulk-Dentsply). Forty two (42) third
      human molars were cut to expose the dentinal surface. They were divided into
      three groups of 14 teeth (GI: XP Bond, G2: Excite, G3: Prime & Bond NT) and two
      groups of seven teeth for each moisture condition: moist dentin (GM) and dry
      dentin, (GD). The total-etch technique was used with each moisture variation. The
      adhesives and composites A3 (Ceram Duo GI, G3 and Tetric Ceram G2) were applied
      according to manufacturer's instructions. Teeth were cut with an ISOMET 1000
      (Buehler Ltd.) to obtain 1 mm2 x 10 mm bars, which were subject to a traction
      test at 5 mm/min in a universal testing machine (Adamel Lhomargy DY 36). The
      collected data were recorded and analyzed using an experimental design for
      studying two factors offixed effrcts with software Statgraphics version 5.1. For
      the variable type of adhesive, we found p = 0.000, for the variable substrate
      condition, p = 0.0012, and for interaction between both factors, p = 0.0457,
      which indicates significant statistical differences. The values for microtensile
      bond strength were G1M = 55.0642 MPa Standard deviation (SD) 3.09768; G1D 39.115
      MPa SD 2.86789; G2M 34.1607 MPa SD 2.86789; G2D = 32.7373 MPa SD 2.77065; G3M 3
      7.3407 MPa SD 2.86789 and G3D = 31.0593 MPa SD 2.77065. XP Bond showed the
      greatest values of micmtensile bond strength under both conditions. Moist
      substrate increases the values of micmtensile bond stren gth]br the adhesives
      tested; howeve, Excite shows lower susceptibility to variation of dentinal
      moisture.

PMID- 19601497
TI  - In vitro analysis of bond strength of self-etching adhesives applied on
      superficial and deep dentin.
AB  - The purpose of this study was to evaluate the bond strength of three adhesive
      systems to superficial and deep dentine using the microtensile bond strength test
      (microTBS). The occlusal enamel of thirty human third molars was removed to
      expose a flat surface of superficial or deep dentin. For each type of surface,
      the test specimens were randomly divided into three groups which underwent the
      application of a conventional two-step adhesive system [Single Bond (SB)] as the
      control group (n=10), a two-bottle self-etching system [One Coat SE Bond (OCSE)]
      (n=10) and a one bottle one-step system [Clearfil S3 Bond (CFS3)] (n=10).
      Adhesives were applied, a 5-mm high "crown" as built-up with resin composite Z250
      (3M) and the specimens with a cross-sectional area of 0.7 +/- 0.1 mm2 were tested
      in tension (0.5 mm/min). Four fractured sticks from each tooth were randomly
      selected and the dentin side was gently abraded with a 1200-grit SiC paper etched
      with 35% phosphoric acid for 15 s and air dried. SEM micrographs at 70X and 2400X
      magnification were taken using scanning electron microscopy (SEM) to calculate
      the area of tubular dentin (ATD) and tubular density (TD) with Image Pro Plus 5.
      Two-way ANOVA (dentin depth-adhesive) showed higher bond strength values for SB.
      However the values did not depend on dentin depth. Linear regression showed a
      significant relationship between bond strength and area of intertubular dentin
      for SB (p = 0.004), and a significant inverse relationship between tubular
      density and bond strength for CFS3 (p = 0.009). OCSE exhibited a tendency that
      was similar to SB and opposite to CFS3, but was not statistically significant.
      The conventional two-step adhesive had higher bond strength values. The use of
      digital image analysis facilitates the manipulation of data and contributes to
      the interpretation of the behavior of new adhesive systems.

PMID- 19601498
TI  - Evaluation of hardness and color stability in the soft lining materials after
      thermocycling and chemical polishing.
AB  - The aim of this study was to evaluate the Shore A hardness and color stability of
      two soft lining materials after thermocycling and when chemical polishing was
      used or omitted. Two acrylic-based soft lining materials were tested: Coe-Soft
      and Soft Confort, 14 specimens were made for each material. They were distributed
      in four groups according to the treatment performed. The specimens were
      thermocycled (1000 cycles) and half of the group submitted to chemical polishing
      (methyl methacrylate). Shore A hardness was determined and color stability was
      calculated by means of Commission International de l'Eclairage Lab uniform color
      scale using a spectrophotometer, the measurements were made immediately after
      deflasked, chemical polishing and thermocycling. Analysis of variance (ANOVA) and
      Tukey's tests were performed at p < 0.01. Color changes (deltaE) were observed
      after thermocycling in both soft lining materials: Soft Confort (10.60) showed
      significantly higher values than Coe-Soft (4.57). Coe-Soft (26.42) showed higher
      Shore A hardness values than Soft Confort (19.42). Chemical polishing did not
      influence in the color stability of both materials; however, influenced in the
      hardness values of Coe-Soft.

PMID- 19601499
TI  - Screening for infectious diseases at international airports: the Frankfurt model.
AB  - Historically, ships brought infectious diseases to the continents of the world,
      but in this modern era, infectious diseases and pandemics are primarily spread
      through aviation as a mode of travel. This is a significant issue in the realm of
      infection control because of the increased potential for the rapid worldwide
      transmission and spread of disease. Although the transmission of infectious
      diseases to airline passengers inside an aircraft is a rare occurrence, it is
      essential to implement entry and exit screening procedures at airports within the
      context of the International Health Regulations (IHR) in order to slow down the
      spread of infection, especially during the early phases of a pandemic event.
      Currently, there are no standardized procedures for health screening at airports,
      thus allowing individual regional authorities to determine what they deem to be
      appropriate screening measures for implementation. In this paper, we will discuss
      a new pragmatic approach for entry and exit screening procedures at international
      airports, propose a new classification system for contacts within the aircraft,
      and discuss changing the fixed enforcement of standardized community mitigation
      measures to the implementation of measures that correspond to specific
      characteristics of individual pathogenic agents. The proposed catalog of
      screening measures is aimed at attaining the goals of the IHR, which states that
      the measures should be reasonable while avoiding inconvenience or harm to
      passengers and should not be any more disruptive to the smooth handling of
      passenger traffic than is necessary.

PMID- 19601500
TI  - Prevention of spread of communicable disease by air travel.
AB  - Mathematical modeling suggests that travel restrictions are likely to have only a
      limited effect on minimizing the spread of disease. Nevertheless, medical
      screening of travelers remains an option to be considered in a risk-reduction
      strategy. Screening of departing and/or arriving travelers are possibilities,
      although the World Health Organization (WHO) favors the former as it is normally
      easier to geographically contain a disease prior to its transmission outside the
      outbreak area. Apart from airport screening, several other related issues require
      consideration, including: transmission of disease on board aircraft; transmission
      of disease in airport terminal buildings; and contact tracing. A major challenge
      is to ensure adequate resources are devoted to pandemic preparedness planning in
      the aviation sector, which may not be fully considered in a national preparedness
      plan. This is because the prevention of accidents occupies most of the attention
      of regulatory aviation authorities, and public health authorities do not always
      see aviation as a priority area. Chief medical officers of regulatory authorities
      may be in a position to facilitate collaboration between the many stakeholders
      involved in preparedness planning for aviation.

PMID- 19601501
TI  - Torso heating of divers in cold water.
AB  - INTRODUCTION: Cold water immersion could compromise both the effectiveness and
      safety of a diver. This paper reports an evaluation of the utility of providing
      external heating to divers in cold water. METHODS: Seven U.S. Navy divers wearing
      semidry suits were submerged in 7.2 degrees C water for 2 h. In the heated
      condition, a total of 35 W was delivered to each of four heating pads (total area
      2477 cm2) placed on the torso of the divers. In the unheated condition, the
      participants received no external heating. RESULTS: The participants believed
      they were more comfortable in the heated, than the unheated condition. However,
      objective data did not support this perception. In fact, heating the torso had a
      significantly detrimental effect on the body's thermoregulatory ability, and
      lacked a positive effect on manual dexterity. Cognitive test performance was not
      affected by the exposure. DISCUSSION: Heating the torso did not have a positive
      effect on diver performance. Moreover, heating the torso of a diver may actually
      increase susceptibility to hypothermia.

PMID- 19601502
TI  - Growth hormone levels after flywheel ergometer exercise: correlation with
      independent variables.
AB  - INTRODUCTION: In-flight muscle mass and strength losses are likely exacerbated by
      low growth hormone (GH) concentrations. Factors associated with exercise may
      foretell resultant GH levels and thereby help blunt future mass and strength
      losses. METHODS: To assess the ability of variables to predict GH variance from
      resistive exercise done on a flywheel ergometer (FE) designed for in-flight
      exercise, subjects (N=17) performed three types of workouts on the device. With a
      randomized design, subjects performed the workouts with the intent to determine
      if changes in post-exercise GH concentrations are impacted by contractile mode
      and workload. Body mass, blood lactate (BLa-) concentrations, and peak angular
      velocity (PAV), average power (AP), and total work (TW) from workouts attempted
      to predict GH variance. Pre-exercise blood draws, and at 1 and 30 min after
      workouts, were used to determine GH concentrations. BLa- levels were measured
      before workouts and at 5 min post-exercise. Delta (8, post-pre) and 30-min post
      workout GH levels served as criterion variables. RESULTS: Multivariate regression
      with an alpha < or = 0.05 yielded the following significant prediction equation:
      deltaGH = 13.64 - 0.014 (body mass) - 0.607 (post-exercise BLa-) + 0.659
      (deltaBLa-) - 0.624(PAV) + 0.653(TW) + 0.147(AP). DISCUSSION: Univariate
      correlations show body mass, deltaBLa-, and TW were the best predictors of
      deltaGH variance. Future research should also attempt to identify additional
      variables that account for the unexplained GH variance from FE workouts.

PMID- 19601503
TI  - Serum hormones in soldiers after basic training: effect of added strength or
      endurance regimens.
AB  - INTRODUCTION: Military personnel are often exposed to training programs and
      operational situations that involve multiple stressors such as caloric deficit,
      sleep deprivation, and prolonged physical effort, which may disturb body
      homeostasis, as indicated by hormonal responses.Therefore, we investigated the
      effects of three training regimens on serum basal hormone concentrations before
      and after the 8-wk basic training (BT) period, and whether possible changes in
      serum basal concentrations are related to changes in endurance and strength
      performance. METHODS: Serum hormone levels were measured in 3 groups of 24 male
      military conscripts before and after 3 different types of training programs:
      normal basic training (NT); BT with added strength training (ST); and BT with
      added endurance training (ET). RESULTS: ET and ST increased their maximal
      strength by 12.9% and 9.1%, respectively, and their VO2max increased by 12.0% and
      8.5%, but the changes did not differ significantly between the groups. Increases
      in serum basal testosterone concentration were observed in all groups (BT by
      16.6%, ST by 16.3%, and ET by 26.6%). Serum basal cortisol concentration
      increased in ST by 11.1%. Serum basal thyroxine concentration decreased by 9.2%
      in NT, 11.9% in ST, and 10.5% in ET. CONCLUSIONS: The increases in strength,
      aerobic capacity, and testosterone after training indicate that the regimens were
      adequate to create positive training responses, especially in the ST and ET
      groups. On the other hand, unexpectedly low strength gains in the ST group during
      BT may be a consequence of too high an amount of endurance-based military
      training.

PMID- 19601504
TI  - Ejection injury to the spine in small aviators: sled tests of manikins vs. post
      mortem specimens.
AB  - INTRODUCTION: This study presents the results of seven aerospace manikin and
      three post mortem human surrogate (PMHS) horizontal deceleration sled tests. The
      objective of this study was to establish a body of baseline data that examines
      the ability of small (fifth percentile) manikins to predict whole-body kinematics
      associated with aircraft ejection, and whether currently available head and neck
      injury criteria are applicable in these situations. METHODS: Subjects were
      exposed to a short-duration local z-axis sled pulse while horizontally seated and
      restrained in an ejection seat. Test subjects included instrumented fifth
      percentile female and male manikins, and two small (163.8 cm, 48.3 kg; 143.5 cm,
      48.6 kg) female and one small (166.2 cm, 54.3 kg) male PMHS. RESULTS: The
      anterior (local x-axis) translations of the PMHS heads were less than those
      observed in the manikin tests, but the local z-axis translations of the PMHS
      heads were greater than those of the manikins. Z-axis translations of the
      manikins' T1 were generally similar to those of the PMHS T1, but the anterior x
      axis translations of T1 were greater in the PMHS. The neck injury criterion (Nij)
      tended to under-predict observed injury (primarily ruptures of the posterior
      ligaments at C4-5, T2-3), and the Beam Criterion (BC) tended to over-predict
      observed injury for small occupants. The USN/USAF neck injury criteria (NIC)
      performed best in predicting the observed injuries. DISCUSSION: Present manikin
      designs do not predict the kinematics of PMHS in ejection tests. Further
      refinement of existing injury criteria is required to accurately predict location
      and severity of ejection-induced injuries.

PMID- 19601505
TI  - Cognitive function and mood during acute cold stress after extended military
      training and recovery.
AB  - INTRODUCTION: Acute cold stress is often accompanied by exposure to other adverse
      factors, such as sleep loss, under-nutrition, and psychological stress that
      singly and together may affect cognitive function. METHODS: The effect of
      moderate cold stress on cognitive function was investigated in 15 male volunteers
      exposed to cold air (10 degrees C) for 4 h after they had completed an intense,
      61-d regimen (U.S. Army Ranger training). The single cohort of volunteers was
      tested on three separate occasions: (1) immediately after completing Ranger
      training; (2) 2 d later when they had partially recovered from training; (3) 108
      d later after full recovery. Documented training stressors included limited sleep
      (approximately 4 h sleep/night), caloric deficit (approximately 850 kcal x d(-1),
      intense physical activity, and psychological stress. RESULTS: Baseline rectal
      temperature fell significantly due to training alone (from 36.6 degrees C +/- 0.1
      to 36.3 degrees C +/- 0.1) and was lower still with acute cold exposure (35.9
      degrees C +/- 0.2). Cognitive function was affected by training alone, as
      indicated by significant decreases in vigilance, four-choice reaction time,
      pattern recognition, symbol-digit substitution, word-list learning, grammatical
      reasoning, and mood prior to exposure to acute cold stress. Mood states were also
      adversely affected, including tension, depression, anger, fatigue, confusion, and
      vigor. Acute cold exposure itself significantly degraded vigilance, overall mood,
      and increased tension. DISCUSSION: Chronic multifactorial stress impaired
      cognitive function and mood; the addition of moderate, acute cold stress further
      degraded vigilance and mood. When such circumstances occur, such as during
      disasters or military operations, measures to prevent adverse cognitive and
      physiological outcomes are recommended.

PMID- 19601506
TI  - Crashes of sightseeing helicopter tours in Hawaii.
AB  - INTRODUCTION: Crashes of sightseeing helicopter flights in Hawaii and the
      resulting tourist deaths prompted the FAA to issue regulations in 1994 specific
      to air tours in Hawaii. Research was undertaken to examine the effect of the 1994
      Rule and to describe the circumstances of such crashes. METHOD: From National
      Transportation Safety Board data, 59 crashes of helicopter air tour flights in
      Hawaii during 1981-2008 were identified; crash investigation reports were read
      and coded. Crashes in 1995-2008 were compared with those in 1981-1994. RESULTS:
      The 1994 Rule was followed by a 47% decrease in the crash rate, from 3.4 to
      1.8/100,000 flight hours. The number of crashes into the ocean decreased from
      eight before the Rule to one afterwards. VFR-IMC crashes increased from 5 to 32%
      of crashes. There were 46 tourists and 9 pilots who died in 16 fatal crashes.
      Aircraft malfunctions, primarily due to poor maintenance, precipitated 34 (58%)
      of the crashes and persisted throughout the 28-yr period. Pilot errors were
      apparent in 23 crashes (39%). Flight from visual to instrument conditions
      occurred in two cases before the Rule and seven cases after. Terrain unsuitable
      for landing was cited in 37 crashes (63%). CONCLUSION: Decreases occurred in the
      overall number and rate of crashes and in ocean crash landings. The increase in
      VFR-IMC crashes may be related to the requirement that tour helicopters fly at
      least 1500 ft. above terrain. Attention is still needed to maintenance, pilot
      training, and restricting flights to operating areas and conditions that enable
      safe emergency landings.

PMID- 19601507
TI  - Ondansetron for the prevention of seasickness in susceptible sailors: an
      evaluation at sea.
AB  - BACKGROUND: Seasickness is a common problem, causing a significant decrement in
      performance among naval crew. In about 20-60% of crewmembers, symptoms appear
      with varying intensity depending on the sea state and the duration of the voyage.
      Recent studies have suggested antiemetic 5HT3 blockers as a possible treatment
      for motion sickness, emphasizing their minor clinical and cognitive side effects.
      The purpose of the present study was to evaluate the 5HT3 blocker ondansetron in
      the prevention of seasickness. METHODS: There were 16 volunteers with a normal
      otoneurologic examination and no previous medical history of inner ear disease or
      vertigo who took part in a double blind, randomized, crossover study. During an
      initial learning phase, the participants practiced on a battery of computerized
      performance tests until their results stabilized. Ondansetron 8 mg or placebo was
      administered 2 h before sailing aboard a 500-ton naval vessel in mild sea
      conditions. Participants did the performance tests and completed a questionnaire
      evaluating their seasickness symptoms 4 h into the voyage. RESULTS: No
      statistically significant reduction of seasickness symptoms was demonstrated
      between ondansetron treatment and placebo (a Wiker score of 2.69 +/- 1.78 and
      2.81 +/- 1.97, respectively). There was no statistically significant difference
      in side effects or the results of the performance tests. CONCLUSION: In this
      study, ondansetron was not found to be beneficial in the treatment of
      seasickness. It could be speculated that the mechanism of nausea in seasickness
      is different from that of toxin-induced nausea.

PMID- 19601509
TI  - Cycle ergometer exercise to counteract muscle atrophy during unilateral lower
      limb suspension.
AB  - INTRODUCTION: Atrophy of the leg muscles is a serious consequence of disuse and
      occurs with prolonged exposure to microgravity. We investigated whether intense
      interval training on a cycle ergometer would prevent muscle changes during
      unilateral lower limb suspension (ULLS). METHODS: This study involved 11 healthy
      men who were divided into 2 groups, one with training on a cycle ergometer (TRN,
      N=6) and the other a control group (CON, N=5). TRN performed intense interval
      training (up to 90% of maximum heart rate) on alternate days during 20 d of
      unloading. Maximum voluntary contraction (MVC) of the quadriceps femoris and
      volume of the thigh muscle were measured before and after unloading. Muscle
      functional magnetic resonance imaging (mfMRI), which reflects the contractile
      activity of the activating muscle, were acquired during submaximal dynamic knee
      extension exercises. RESULTS: The MVC was significantly decreased in TRN (-11.1%)
      and CON (-18.7%). The total volume of the thigh muscles was maintained in TRN (
      0.2%); however, a significant decrease was found in CON (-6.9%). The mfMRI signal
      increase for submaximal exercise did not change for TRN; however, it
      significantly increased for CON. CONCLUSIONS: Although the power of this study
      was limited, these results suggest that training on a cycle ergometer counteracts
      some of the effects of unloading and merits further study as a potential
      countermeasure for muscle changes in microgravity.

PMID- 19601508
TI  - Pilot age and error in air taxi crashes.
AB  - INTRODUCTION: The associations of pilot error with the type of flight operations
      and basic weather conditions are well documented. The correlation between pilot
      characteristics and error is less clear. This study aims to examine whether pilot
      age is associated with the prevalence and patterns of pilot error in air taxi
      crashes. METHODS: Investigation reports from the National Transportation Safety
      Board for crashes involving non-scheduled Part 135 operations (i.e., air taxis)
      in the United States between 1983 and 2002 were reviewed to identify pilot error
      and other contributing factors. Crash circumstances and the presence and type of
      pilot error were analyzed in relation to pilot age using Chi-square tests.
      RESULTS: Of the 1751 air taxi crashes studied, 28% resulted from mechanical
      failure, 25% from loss of control at landing or takeoff, 7% from visual flight
      rule conditions into instrument meteorological conditions, 7% from fuel
      starvation, 5% from taxiing, and 28% from other causes. Crashes among older
      pilots were more likely to occur during the daytime rather than at night and off
      airport than on airport. The patterns of pilot error in air taxi crashes were
      similar across age groups. Of the errors identified, 27% were flawed decisions,
      26% were inattentiveness, 23% mishandled aircraft kinetics, 15% mishandled wind
      and/or runway conditions, and 11% were others. CONCLUSIONS: Pilot age is
      associated with crash circumstances but not with the prevalence and patterns of
      pilot error in air taxi crashes. Lack of age-related differences in pilot error
      may be attributable to the "safe worker effect."

PMID- 19601510
TI  - Tuberous sclerosis in a military pilot.
AB  - Tuberous sclerosis (TS) is a multisystem disorder characterized by hamartomas in
      various organs. It usually manifests itself during infancy or childhood with
      neurological features, including mental retardation and seizures. We present the
      case of a military pilot who was diagnosed with TS at 22 yr. of age after he had
      completed flight training. Suspicion of TS arose from evaluation of a chronic
      rash around the pilot's nose, and diagnosis was confirmed based on the presence
      of multiple calcified nodules on CT imaging of the brain. No neurological
      abnormalities were found. The primary aeromedical concerns were the risk of
      seizures or development of tumors at sites that might lead to sudden
      incapacitation. Hamartomas can be reliably detected at an early stage by means of
      annual history, physical examination, and imaging of tumor-prone organs. After
      review of the literature and consultation with medical specialists, we assessed
      the risk of adult-onset seizures in a TS patient without preexisting neurological
      findings as scarce. The pilot was therefore granted a waiver limited to flying a
      two-pilot helicopter with a program of tight medical follow-up.

PMID- 19601511
TI  - Endoscopic frontal sinus drillout for recurrent barotrauma: a procedure to save a
      pilot's career.
AB  - INTRODUCTION: Complete sphenoethmoidectomy with a Draf IIA frontal dissection is
      the standard of care surgical management for medically resistant diffuse
      recurrent sinus barotrauma. Surgical failures still occur with this technique
      mainly due to the propensity of the frontal outflow tract to stenose. Endoscopic
      frontal revisions are notoriously prone to failure and historically represented
      the only option for aircrew afflicted by this career-ending complication of
      surgery. The frontal sinus drillout or endoscopic modified Lothrop procedure
      (EMLP) offers a highly successful salvage surgery for postoperative frontal
      ostium stenosis and is particularly suited to the physiologic requirements of the
      aviator. CASE: A high-performance aircraft pilot developed frontal stenosis after
      extensive sinus surgery for recurrent sinus barotrauma. Multiple failed
      endoscopic attempts to rehabilitate his sinuses finally gave way to success using
      the EMLP. He was returned permanently to flight duty at 6 wk post-op. DISCUSSION:
      This case report represents the first published successful application of the
      modified endoscopic Lothrop procedure to a pilot with recurrent frontal sinus
      barotrauma.

PMID- 19601512
TI  - Leisure pilot license proposed for Europe: do you want such pilots crossing your
      flight path?
AB  - In a Notice of Proposed Amendment, the European Aviation Safety Agency proposes
      to introduce a Leisure Pilot License (LPL). Holders of a LPL for airplanes will
      be allowed to fly single-engine piston airplanes with a maximum takeoff mass of
      2000 kg or less, carrying a maximum of three passengers. In this commentary
      paper, we express significant concern about the flight safety consequences of the
      proposed aeromedical requirements of the LPL. We argue that the proposed minimum
      age, validity period of the medical certificate, and issuance of certificates by
      general practitioners may increase the flight safety risk. Major revision of the
      proposed LPL regulation is recommended.

PMID- 19601513
TI  - Hyperstereopsis associated with helmet-mounted sighting and display systems for
      helicopter pilots.

PMID- 19601515
TI  - Vishniac W. Extraterrestrial microbiology. Aerosp Med 1960; 31:678-80.

PMID- 19601514
TI  - You're the flight surgeon. Prostate cancer, erectile dysfunction, and seizure.

PMID- 19601516
TI  - Humans in the air and space--looking beyond 2020.

PMID- 19601517
TI  - [The effectiveness of measurement of nasal resistance in patients with sleep
      disordered breathing].
AB  - Nasal breathing disorder has been associated with the condition and treatment of
      sleep disordered breathing (SDB). In the current study, we investigated the
      utility of measurement of nasal resistance in patients with SDB. We examined the
      relationship between nasal symptoms and nasal resistance in 219 patients, and how
      the results affected the administration of nasal continuous positive airway
      pressure (nCPAP) in 34 SDB patients. Total nasal resistance was not significantly
      different between patients who were divided into two groups: those with nasal
      symptoms, and those without. The left-right ratio of nasal flow in the group with
      nasal symptoms was higher than in the group without nasal symptoms (p < 0.01).
      The mean percentage of nCPAP use was not significantly different between two
      groups divided by total nasal resistance. The mean percentage of nCPAP use > or =
      4 hours was lower in the group in which total nasal resistance was more than
      0.25Pa/cm3/sec (p < 0.05). The left-right ratio of nasal flow does not affect
      nCPAP use. We conclude that measurement of nasal resistance for confirming nasal
      breathing disorder is effective in patients with SDB, whether a patient complains
      of nasal symptoms or not.

PMID- 19601518
TI  - [Clinical case study of lung cancer accompanied by pulmonary aspergillosis].
AB  - We retrospectively studied clinical cases of lung cancer complicated by pulmonary
      aspergillosis. A total of 19 cases with average age of 69.5 years were
      encountered over the last 9 years. All had a history of smoking and 18 were men.
      In 2 cases, pulmonary aspergillosis and lung cancer were diagnosed concurrently.
      Pulmonary aspergillosis was diagnosed first in 4 cases and lung cancer was
      diagnosed first in 13 cases, in 11 of which pulmonary aspergillosis developed
      after surgery for lung cancer. In the non-operated group 5 cases had
      complications at the same site and 3 had complications at a different site. In
      the operated group, 10 cases subsequently had ipsilateral pulmonary aspergillosis
      and 1 case had contralateral pulmonary aspergillosis. Thirteen cases received
      antifungal medication. Lung cancer therapy is a risk factor for pulmonary
      aspergillosis. Careful medication is recommended.

PMID- 19601519
TI  - [Qualitative analysis of interns' decision-making process of selecting
      respiratory medicine as their specialty].
AB  - BACKGROUND: Because there is a shortage of pulmonologists in Japan, it is crucial
      to understand interns' decision-making process of selecting respiratory medicine
      as their specialty. OBJECTIVE: The objectives of the study were to illustrate the
      process in which residents pursue the specialty of respiratory medicine and to
      establish a strategic springboard that may encourage more residents to select
      respiratory medicine as their specialty. METHODS: A qualitative study using semi
      structured interviews was performed. Eleven doctors who had selected respiratory
      medicine were recruited. We measured categories which constitute the process of
      career choice. RESULTS: The present analysis of 11 interviews produced three main
      categories that influenced residents' career decision. Those were "ambiguous
      preference for respiratory medicine", "triggers for interests on respiratory
      medicine", and "comparisons and contemplations among specialties". "Triggers for
      interests" were as follows: experiencing effectual mentorship in respiratory
      medicine, being impressed with pulmonologists' daily practice, taking an interest
      in anatomy and physiology, and exposing themselves to clinical practice
      repeatedly. Through "comparisons and contemplations among specialties", the
      interviewees recognized respiratory medicine as attractive, because of its close
      association with other internal medicine disciplines, the comprehensive
      diagnostic process, and the diversity of respiratory diseases. CONCLUSION:
      Experiencing enthusiastic mentorship, being impressed with pulmonologists' daily
      practice, and realizing profoundness of respiratory medicine influenced the
      decision-making process.

PMID- 19601520
TI  - [A case of pulmonary dirofilariasis diagnosed by biopsy, immunological tests and
      the clinical course without operation].
AB  - A 52-year-old woman who was a pet trimmer by occupation and had four cats,
      presented with cold-like symptoms. Her chest radiograph and CT scan on admission
      showed a tumor about 4cm in size with spicula and ground-glass opacity in the
      right middle lobe. We performed fiberoptic bronchoscopy and CT-guided
      percutaneous needle lung biopsy on the suspicion of lung cancer, but the tissue
      consisted largely of granulation tissue with eosinophilic infiltration and no
      findings of malignancy. The cold-like symptoms subsided and C-reactive protein
      became within the normal range. Because of the histological findings, her
      occupation and her pets, we suspected pulmonary dirofilariasis. We asked the
      National Institute for Infectious Diseases for specific IgG antibody assays to
      various parasite antigens, which showed positive finding for pulmonary
      dirofilariasis. We therefore diagnosed pulmonary dirofilariasis and did not
      perform an operation.

PMID- 19601521
TI  - [A case of fulminant Mycoplasma pneumoniae pneumonia despite adequate antibiotic
      treatment].
AB  - A 35-year-old woman complaining of fever and cough consulted a local clinic. She
      did not recover despite treatment with oral azithromycin, and a chest X-ray
      demonstrated infiltrates in both lungs. She was then admitted to our hospital and
      treated with intravenous pazufloxacin and oral clarithromycin. However, she did
      not respond to the treatment and her respiratory condition deteriorated.
      Thereafter, she was treated with high doses of corticosteroids, and her condition
      rapidly improved radiologically and clinically. The diagnosis was confirmed to be
      Mycoplasma pneumoniae pneumonia by the increased antibody-titer and positive M.
      pneumoniae PCR of bronchoalveolar lavage. In summary, we encountered a case of
      severe M. pneumoniae pneumonia, which induced acute respiratory failure even
      though the patient was receiving appropriate antibiotic treatment. The patient
      was recovered with steroid pulse therapy.

PMID- 19601522
TI  - [A case of Candida glabrata empyema].
AB  - A 72-year-old man was admitted to our hospital because of a low grade fever and
      malaise. He had received a middle to lower esophagectomy and proximal gastrectomy
      with reconstruction of a gastric conduit for esophageal cancer 12 years
      previously. Chest X-ray and CT scan revealed massive pleural effusion and
      consolidations on the right side. Candida glabrata was isolated 4 times from
      pleural fluid specimens. Candida antigen was negative in both serum and pleural
      effusion. However, while serum beta-D-glucan was negative, the level of beta-D
      glucan in pleural effusion was extremely elevated. Thus, the patient was
      diagnosed as having C. glabrata empyema. He was treated with insertion of a
      thoracostomy tube followed by intrapleural instillation of amphotericin B and
      intravenous administration of micafungin. Pleural effusion was reduced and the
      repeated culture of the pleural effusion became negative after 27 days of
      treatment. Empyema with C. glabrata is rare and the present case is the second
      report of the disease in the Japanese literature.

PMID- 19601523
TI  - [A case of severe radiation pneumonitis--a trial of plasma exchange].
AB  - A 77-year-old man underwent radiotherapy for the squamous cell carcinoma of the
      right lung. Two months after the 60Gy/30fr irradiation was completed, he
      complained of dyspnea and his chest X-ray showed ground glass opacities and
      reticular shadows in both lung fields. Severe radiation pneumonitis was
      diagnosed. Two grams of methylprednisolone did not improve his symptoms and on
      the next day his hypoxemia worsened. We then tried plasma exchange because of his
      critical status. His respiratory status improved rapidly after plasma exchange
      and his chest X-ray showed remarkable improvement 10 days later. We think this
      case suggests the effectiveness of plasma exchange for severe radiation
      pneumonitis.

PMID- 19601524
TI  - [A case of Sjogren syndrome with nifedipine-induced pneumonia].
AB  - A 54-year-old woman started to take nifedipine orally for hypertension on
      February 18, 2006. From April 10, 2007, fever, tachycardia and chest pain
      appeared. Chest radiography showed a consolidation shadow in the right upper
      lobe. Administration of antibiotics was started because bacterial pneumonia was
      suspected. After the administration of antibiotics, the condition of the patient
      was aggravated and the consolidation shadow in the chest radiograph increased.
      Consequently, she was hospitalized for examination. Transbronchial lung biopsy
      was carried out on April 27, 2008. Pathological analysis revealed organization
      and inflammatory cell infiltration was observed in alveoli. Eosinophils were
      increased in the bronchial washing fluid. After halting administration of all
      drugs, the fever was alleviated. Since nifedipine was positive in DLST, drug
      induced pneumonia caused by nifedipine was diagnosed. Salivary-gland biopsy was
      carried out on May 25, 2008 on the suspicion of Sjogren syndrome, because she
      continued to complain of dryness in the mouth and eyes. The pathological findings
      were consistent with Sjogren syndrome. To the best of our knowledge, there has
      been no report of drug-induced pneumonia caused by nifedipine. Since the case was
      complicated with Sjogren syndrome, some immunological dysregulation might have
      been a factor. In cases of lung impairment caused by a drug, it is necessary to
      consider the possibility of a immunologic disorder.

PMID- 19601526
TI  - [A case of multicentric Castleman's disease with pulmonary involvement].
AB  - A 46-year-old man with polyclonal hypergammaglobulinemia was admitted to our
      hospital because of an abnormality on his chest radiograph findings. His chest CT
      showed a localized ground-glass opacity 21 mm in size in the right upper lobe,
      and some small nodules in all lung fields. He underwent video-assisted
      thoracoscopic surgery to establish a diagnosis. The histopathologic findings of
      the surgical specimens revealed the infiltration of lymphocytes and plasma cells.
      We diagnosed multicentric Castleman's disease. He did not wish to be treated
      because he had no symptoms. We took a wait-and-see approach and carefully
      followed him up. Multicentric Castleman's disease is extremely rare.

PMID- 19601525
TI  - [A case of Legionella pneumonia with diabetic ketoacidosis rescued despite the
      development of acute renal failure and ARDS].
AB  - A 57-year-old man was admitted to our hospital complaining of general fatigue and
      appetite loss. The initial chest radiograph showed infiltration in the left upper
      lung field. Cefozopran was administered. Concomitant diabetic ketoacidosis was
      treated with hydration and rapid-acting insulin. However he was intubated and
      ventilated because of deteriorated respiratory condition and ketoacidosis on the
      3rd hospital day. Urinary legionella antigen was detected the same day, therefore
      ciprofloxacin and imipenem were initiated. On the 4th hospital day, he developed
      acute renal failure and was treated with continuous hemodiafiltration. In
      addition, he developed adult respiratory distress syndrome on the 6th hospital
      day, therefore siveletat sodium was given. The patient gradually began to improve
      and was extubated on the 17th hospital day. After that he was transferred to the
      metabolic ward on the 24th hospital day for control of his diabetes mellitus.
      Despite the severe complications in his clinical course, including diabetic
      ketoacidosis, acute renal failure and ARDS, detection of Legionella pneumophila
      by a urinary antigen test, Gimenez stain and sputum culture made prompt and
      proper administration of antibiotics possible, finally yielding a desirable
      outcome.

PMID- 19601527
TI  - [Sarcoidosis presenting after successful treatment for Cushing syndrome].
AB  - A 37-year-old woman was referred to our department because of an abnormal shadow
      on her chest radiograph as well as multiple subcutaneous nodules on both her
      lower legs. She had had a history of Cushing syndrome due to right adrenal
      adenoma, which was successfully treated by unilateral adrenalectomy two years
      before her admission to our department; however, the chest radiographic
      abnormalities and the skin lesions were not apparent at that time. According to
      our findings, her chest CT showed bilateral hilar and mediastinal
      lymphadenopathy, irregular thickening of bronchovascular bundles, interlobular
      septal thickening, and centrilobular micronodules. Skin biopsy specimens
      demonstrated noncaseating epithelioid cell granuloma, which was consistent with
      the diagnosis of sarcoidosis. An elevated angiotensin-converting enzyme level and
      increased accumulation of gallium-67 citrate in the pulmonary parenchyma and
      hilar lymph nodes also supported the diagnosis. She received no further steroid
      therapy for the sarcoidosis, and the clinical findings have been improving. In
      this case, we speculate that sarcoidosis might have been exacerbated by a
      reduction in the endogenous steroid levels after the unilateral adrenalectomy for
      Cushing syndrome. We should be aware of the possibility of the condition that
      steroid-responsive immune diseases such as sarcoidosis might be unmasked and
      develop after successful treatment for Cushing syndrome.

PMID- 19601528
TI  - [Pleomorphic carcinoma of the lung with uncommon initial manifestation of
      intestinal perforation].
AB  - A 47-year-old woman suddenly developed abdominal pain and visited the emergency
      room of our hospital. Chest and abdominal CT scan revealed free air in the
      abdominal cavity and a bulky pulmonary tumor in the right middle lobe. The
      perforated sigmoid colon was removed in an emergency operation. Histological
      examination of the resected tissue revealed undifferentiated carcinoma, but the
      histological differentiation could not be determined. We used immunohistochemical
      staining to distinguish primary non-small cell lung cancer from colon cancer; the
      resected tumor was positive for TTF-1 and CK7, but negative for CK20. Therefore,
      by using immunohistochemical staining we could diagnose the tumor of the large
      intestine as metastasis from non-small cell lung cancer. After the operation,
      systemic chemotherapy with carboplatin and docetaxel was repeated, but the lung
      tumor did not regress and the patient died. Autopsy examination confirmed the
      histology of the lung tumor as pleomorphic carcinoma. Morphological
      characteristics and the immunohistochemical staining pattern of the pulmonary
      tumor were consistent with that of the colon tumor. In Japan, this is the first
      report in which the initial manifestation of lung cancer was perforation of the
      large intestine due to metastasis.

PMID- 19601530
TI  - [An autopsy case of pulmonary tumor thrombotic microangiopathy complicated with
      interstitial pneumonia and lipoid pneumonia].
AB  - A 67-year-old woman was admitted to our hospital because of progressive dyspnea,
      cough, bloody sputum, and backache. Chest radiography and CT scans showed
      bilateral diffuse interstitial shadows, bilateral pleural effusion and dilatation
      of the pulmonary artery. Echocardiography indicated pulmonary hypertension, and
      the serum tumor marker levels were elevated. We performed right cardiac
      catheterization, and withdrew some blood from a pulmonary artery catheter in the
      wedge position. We confirmed moderate pulmonary hypertension, and adenocarcinoma
      like malignant cells were seen in the aspirated blood. The patient died of
      progressive respiratory failure despite supportive care. In addition to PTTM and
      lymphangiosis carcinomatosa, autopsy of the right lung revealed interstitial
      pneumonia and lipoid pneumonia, both of which were not reported before to be
      associated with PTTM.

PMID- 19601529
TI  - [An autopsied case of mucinous bronchioloalveolar carcinoma associated with
      multiple thin-walled cavities].
AB  - A 82-year-old man was found to have mucinous bronchioloalveolar carcinoma
      associated with a cavity 10-cm in size in the right lower lobe, and he underwent
      a surgical lobectomy in April 2005 (pT2N0M0). Seven months after the surgery,
      chest images showed multiple metastases with thick-walled cavities in bilateral
      lung fields. The serial HRCT showed that thick-walled cavity lesions transformed
      into thin-walled cystic cavities associated with decreasing serum CEA levels. The
      patient's condition was good with best supportive care for 24 months from the
      time of recurrence. Subsequent progression of the thick-walled cavities into thin
      walled cavities, was acompanied by re-elevation of serum CEA levels, and he died
      of respiratory failure 5 months after re-exacerbation. Macroscopic findings at
      autopsy showed multiple cavities in both lungs. Microscopic findings of the right
      lung showed desquamative mucinous bronchioloalveolar carcinoma cells lining the
      thick-walled cavity surface, and a single layer of tumor cells proliferating in
      the thin-walled cavity surface. Tumor cells with excessive mucus and necrosis
      were observed in the thick-walled cavities. It is suggested that thick-walled
      cavities were formed as a result of avascular necrosis and destruction of the
      pulmonary alveoli by excessive mucus, and thin-walled cavities were formed as a
      result of a check-valve mechanism.

PMID- 19601531
TI  - [A case of MALT lymphoma simultaneously associated with gastric and pulmonary
      involvement].
AB  - A 52-year-old man had been treated by hemodialysis because of IgA nephropathy
      since 1994. Gastric MALT lymphoma was diagnosed in January 2007. Radiation
      therapy was performed for 4 weeks (40Gy) and the response was complete remission
      (CR) by September 2007. He was admitted to our hospital in February 2008 because
      of an abnormal chest shadow. Chest CT showed multiple cystic lesions with
      calcification and consolidation. Transbronchial lung biopsy from the area of
      consolidation (left S5) showed pulmonary invasion of small lymphoid cells. PCR
      analysis showed clonal rearrangement of the heavy chain of the immunoglobulin
      gene. Accordingly, MALT lymphoma was diagnosed. Rituximab infusion was performed,
      because CD20 immunostaining was positive and he had been treated by hemodialysis.
      The abnormal chest shadow was presented since gastric MALT lymphoma was
      diagnosed. We considered that MALT lymphoma occurred simultaneously in the
      stomach and lung.

PMID- 19601532
TI  - [A case of pleural sarcoidosis with bilateral pleural effusion].
AB  - A 25-year-old man was referred to our hospital because of cough and an abnormal
      shadow on chest X-ray film showing bilateral hilar lymphadenopathy accompanied by
      multiple nodules in both lung fields. A transbronchial lung biopsy demonstrated
      non-caseating epithelioid cell granulomas, and we diagnosed sarcoidosis. He was
      observed without medication for 18 months, however, his chest X-ray film findings
      gradually worsened, and bilateral pleural effusion appeared. The pleural effusion
      consisted of exudative fluid with prominent lymphocytes, and ADA level was
      elevated to 57.0U/l. Thoracoscopy demonstrated multiple whitish granulations on
      the parietal and visceral pleura. The pleural biopsy specimens exhibited non
      caseating epithelioid cell granulomas, and there was no evidence of acid-fast
      bacilli. Based on these findings, pleural sarcoidosis was diagnosed. He was
      treated with 30 mg oral prednisolone daily, and both pleural effusion and nodules
      of lung fields on chest X-ray film subsided. Sarcoidosis with bilateral pleural
      effusions is rare, and we discuss this condition in relation to the pertinent
      literature.

PMID- 19601534
TI  - [A case of mesalazine-induced lung injury improved by only discontinuation of
      mesalazine].
AB  - We reported a case of drug-induced lung injury associated with mesalazine. A 50
      year-old woman was diagnosed as having ulcerative colitis and treated with
      mesalazine. After administration for 1 month, the patient developed dry cough,
      fever and bilateral pulmonary infiltrates. A bronchoalveolar lavage showed 6.5 x
      10(5) cells/ml, with 58% lymphocytes and 20% eosinophils. Improvement in clinical
      symptoms and radiological abnormalities occurred spontaneously after
      discontinuation of mesalazine. Even though the signs and symptoms of mesalazine
      induced lung injury are similar to those of the pulmonary involvement of
      inflammatory bowel disease, it is important to distinguish them differences.

PMID- 19601533
TI  - [A case of primary pulmonary nocardiosis with multiple pulmonary nodules
      successfully treated with moxifloxacin].
AB  - A 18-year-old man was admitted with fever. His chest radiograph and CT scan
      showed consolidation shadow in the right middle lobe and multiple nodules in both
      lungs. He was treated with meropenem and minocycline. After this antibiotic
      therapy, the consolidation shadow disappeared and the multiple nodules were
      slightly reduced in their size. Since filamentous bacteria suspicious of Nocardia
      grew transiently in the initial sputum culture, we started to treat him with oral
      sulfametoxazole-trimethoprim. However, because agranulocytosis was caused by
      sulfametoxazole-trimethoprim therapy, we had to change the anti-bacterial therapy
      to minocycline. Minocycline was not effective, and the nodules enlarged. For
      accurate diagnosis, we employed video-assisted thoracic surgery (VATS) to
      investigate the histological and bacterial analyses of the pulmonary nodules.
      Histological findings of the pulmonary nodule obtained by VATS revealed granuloma
      with central necrosis associated with neutrophilic micro-abscess. Filamentous
      gram-positive bacteria in pulmonary nodule tissue was stained positively with
      both Grocott and Ziehl-Neelsen staining. Taking these findings together, we
      diagnosed primary pulmonary nocardiosis. Three months after initiating
      moxifloxacin, the size of the multiple pulmonary nodules was markedly reduced.
      Our experience with this case suggests that moxifloxacin can be recommended for
      the treatment of pulmonary nocardiosis.

PMID- 19601536
TI  - [Main events I have experienced as chairman of Japanese Society for Clinical
      Toxicology].

PMID- 19601535
TI  - [Primary pulmonary cryptococcosis with multiple infiltrative shadows complicated
      by obstructive sleep apnea syndrome].
AB  - In November 2007, a 30-year-old obese woman was admitted to our hospital with a
      complaint of persistent dry cough. Her chest-X-ray and computed tomography
      revealed multiple infiltrative shadows with air bronchograms in all lung fields.
      The bronchoalveolar lavage fluid revealed small bodies of Cryptococcus species.
      Cryptococcal serum antigen was also positive. To examine the cause of her
      snoring, polysomnography was done and revealed obstructive sleep apnea syndrome.
      The patient was given a diagnosis of primary pulmonary cryptococcosis with
      obstructive sleep apnea syndrome. After 12 months of treatment with fluconazole,
      the infiltrative shadows disappeared. Pulmonary cryptococcosis should be
      considered in the differential diagnosis of pulmonary multiple infiltrated
      shadows in patients without immunological abnormalities.

PMID- 19601537
TI  - [Remembering to my period of chairman, board of directors, Japanese Society for
      Clinical Toxicology].

PMID- 19601538
TI  - [Review of the course during last 6 years as a secretary general for Japanese
      Society for Clinical Toxicology].

PMID- 19601539
TI  - [As a chairperson of our association's 30th memorial round-table talk].

PMID- 19601540
TI  - [Analysis of bialaphos and its active metabolite L-glufosinate in biological
      specimens by HPLC].
AB  - The symptoms of acute poisoning caused by ingestion of bialaphos (BIAL), an
      ingredient of herbicide, are supposed to be due to the L-glufosinate (L-GLUF),
      which is formed by the degradation of bialaphos. To elucidate the
      pharmacokinetics of BIAL and L-GLUF, we attempted a simultaneous analysis of BIAL
      and L-GLUF in biological samples by exploiting a reversed phase HPLC method. The
      derivatization reaction of BIAL and L-GLUF using (+) -1- (9-fluorenyl) ethyl
      chloroformate was completed in 30 min at 40 degrees C and both derivatives were
      stable for 48 hr at 25 degrees C. A fluorescence detector were used for HPLC; the
      exicitation wavelength was set at 265 nm and the emission wavelength at 315 nm.
      Respective calibration curves prepared by adding BIAL and L-GLUF to serum were
      linear within ranges of 0.01-10.0 and 0.005-10.0 microg/mL in derivatived liquid
      samples for introducing into HPLC. The lower limits of detection for BIAL and L
      GLUF were 0.005 and 0.001 microg/mL, respectively. An 83-year old male who
      ingested approximately 350 mL of Herby Liquid, a herbicide containing 18% BIAL
      and 82% surfactant, in an attempt to commit suicide developed delayed respiratory
      depression and seizures. L-GLUF was detected in the serum of the patient 2.7 hr
      after ingestion, but BIAL was not. The change in serum L-GLUF concentration
      measured over time was consistent with a 2-compartment model, with a distribution
      half-life of 1.70 hr and an elimination half-life of 6.03 hr.

PMID- 19601541
TI  - [Suicide case of carbon dioxide poisoning using dry ice].
AB  - We had a suicide case suspected to result in death from carbon dioxide poisoning
      by dry ice in the car. A clay cooking stove with charcoal was in the car, but the
      charcoal had no burning sign. CO hemoglobin saturation degree of the suicide
      victim's blood was 0%. Moreover, there were signs that 50 kg of dry ice was
      brought in the car. To clarify the cause of death, reproducibility testing was
      carried out by using a car under the same conditions. CO2 concentration in it
      increased to 22% and O2 concentration decreased to 16% within 20 minutes. From
      these observations, his death was considered to be caused by hypoxia and CO2
      narcosis. CO2 in the suicide victim's blood was higher than those in the blood of
      healthy persons, and the same range was visible in the blood of fire victims.
      These data might support above supposition concerned with the cause of death.
      Blood analysis will be helpful in clearing the cause of death by CO2 poisoning.

PMID- 19601542
TI  - [Current topics and problems in toxicology laboratories--4].

PMID- 19601543
TI  - [Iizuka Hospital Central Laboratory Toxic Drugs and Chemicals Analysis Team].

PMID- 19601544
TI  - [Department of Forensic Medicine, Graduate School of Biomedical Sciences,
      Hiroshima University].

PMID- 19601545
TI  - [Etiology of essential hypertension: role of the kidney].

PMID- 19601546
TI  - [Extrarenal mechanisms for essential hypertension].

PMID- 19601547
TI  - [Novel evidence for sodium sensitivity and renal impairment].

PMID- 19601549
TI  - [Sympathetic activity and nephropathy].

PMID- 19601548
TI  - [Development of hypertension and RAAS].

PMID- 19601551
TI  - [Contribution of diuretics to the treatment of hypertension in patients with
      CKD].

PMID- 19601550
TI  - [Principal entity of hypertension version of CKD guide].

PMID- 19601552
TI  - [Efficacy of calcium channel blocker in hypertensive patients with chronic kidney
      disease].

PMID- 19601553
TI  - [Points at issue in the Japanese Society of Hypertension's Guidelines for the
      Management of Hypertension (JSH2009)].

PMID- 19601554
TI  - [Positioning of CKD in risk stratification].

PMID- 19601555
TI  - [Perfect 24-hr blood pressure control using self-measured blood pressure and
      ambulatory blood pressure monitoring in chronic kidney disease].

PMID- 19601556
TI  - [Treatment of elderly hypertension].

PMID- 19601557
TI  - [Analysis of metabolic syndrome and pulse wave velocity in hemodialysis patients:
      diagnosis of obesity by bioelectrical impedance analysis and a novel risk factor
      for atherosclerosis].
AB  - PURPOSE: Metabolic syndrome (Met S) is one of the risk factors of atherosclerotic
      vascular diseases related to visceral fat accumulation. However, it is well known
      that morbidity and mortality of hemodialysis (HD) patients are associated with
      malnutrition and emaciation rather than obesity, representing "reverse
      epidemiology". The risk of visceral fat accumulation or Met S in HD patients
      remains unclear. Therefore, we evaluated atherosclerosis and Met S in HD patients
      using various markers of obesity by means of bioelectrical impedance analysis
      (BIA) and brachial-ankle PWV(baPWV). METHODS: The subjects comprised 52 patients
      who were undergoing maintenance dialysis. In addition to a general physical
      examination and routine blood tests, immunoreactive insulin (IRI), homeostasis
      model assessment for insulin resistance (HOMA-R), serum adiponectin (ADPN) and C
      reactive protein (CRP)were measured before dialysis. Furthermore, we measured
      various body fluid components, such as the ratio of extracellular water to total
      body water (ECW/TBW), body fat mass (BFM), percent body fat(PBF) and visceral fat
      accumulation (BIA-VFA), using a body composition analyzer (InBody S20)and baPWV
      as a marker of atherosclerosis. RESULTS: There was no significant difference
      between HD patients with and without Met S for baPWV. baPWV was positively
      correlated with age, systolic BP and ECW/TBW, and negatively correlated with
      serum albumin level, BMI and serum ADPN. However, no significant correlations
      were observed between baPWV and the durations of HD, Ca x P product, BIA-VFA,
      PBF, HOMA-R and CRP. The serum ADPN level was significantly lower in Met S than
      in non-Met S. In addition, the ADPN level was positively correlated with HDL
      cholesterol, and negatively correlated with TG, HbA1c, CRP and various markers of
      obesity (Waist, BIA-VFA, BFM and PBF). In a multiple regression analysis for
      baPWV, the ECW/TBW ratio and serum ADPN level, as well as age and systolic BP,
      were independent predictors for the enhancement of baPWV in HD patients.
      CONCLUSION: The present study demonstrated that the ECW/TBW ratio and low serum
      ADPN level, but not Met S or obesity, could be risk factors for the acceleration
      of atherosclerosis in HD patients. In addition, the results showed that the
      relationship between ADPN,as an anti-atherosclerotic factor, and body fat or
      lipid metabolism were also maintained in HD patients.

PMID- 19601558
TI  - [Case of Henoch-Schonlein purpura nephritis successfully treated with
      tonsillectomy and steroid pulse therapy].
AB  - A 30-year-old Japanese man was admitted to our hospital because of fever, sore
      throat, abdominal pain, purpura skin lesion of the lower legs, and
      macrohematuria. On admission, his urine was positive (++) for protein; the
      sediment contained 100 red blood cells per high-power field, and the daily
      proteinuria level was 1.7 g. Renal biopsy was performed, and we diagnosed Henoch
      Schonlein purpura nephritis (HSPN). Six months after the renal biopsy, the
      patient underwent a tonsillectomy. The pathological diagnosis of the resected
      tonsils was chronic tonsillitis. After tonsillectomy, the daily proteinuria had
      decreased to 0.1 g and the sediment contained only 10-19 red blood cells per high
      power field. High-dose methylprednisolone therapy (500 mg/day for 3 days for
      three courses) was started two weeks after the tonsillectomy, followed by oral
      prednisolone at the initial dose of 30 mg on alternate days. The oral
      prednisolone was tapered gradually over 1 year. Antiplatelet drug (dipyridamole,
      300 mg/day) and angiotensin II receptor antagonist (olmesartan, 10 mg/day) were
      also administered. This combination therapy resulted in a significant decrease in
      proteinuria and disappearance of microhematuria. The patient finally achieved
      clinical remission. Recent reports have shown that in patients with IgA
      nephropathy, combined tonsillectomy and methylprednisolone pulse therapy have an
      effect on clinical remission. In addition, it has been suggested that HSPN and
      IgA nephropathy represent a spectrum of clinical presentations of similar
      disorders. The result of this case indicated that this combination therapy had a
      favorable effect on clinical remission in adult patients with HSPN.

PMID- 19601559
TI  - [Case of rapidly progressive glomerulonephritis with anti-glomerular basement
      membrane antibody in the course of MPO-ANCA-associated pachymeningitis].
AB  - A 56-year-old female developed rapidly progressive glomerulonephritis in the
      course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)
      associated pachymeningitis that had been found four years previously. On
      admission, her serum creatinine increased from 0.8 mg dL to 1.84 mg dL and to
      3.66 mg dL every 3 to 4 weeks. Urinalysis revealed that urinary protein excretion
      was 1.25 g day and 3+ hematuria. MPO-ANCA titer was found to be 50 EU and anti
      glomerular basement membrane (GBM) antibody was also elevated to as high as 174
      EU. Renal pathology revealed cellular to fibrocellular crescents in 21 out of 23
      glomeruli with interstitial inflammation and fibrosis. Immunohistochemistry with
      anti IgG antibody showed linear staining along the glomerular capillary walls.
      Following plasma exchange and methylprednisolone pulse therapy, oral prednisolone
      at a dose of 50 mg day was instituted, but without significant effect. Subsequent
      cyclophosphamide pulse therapy was effective, resulting in the stabilization of
      serum creatinine at 2 mg dL and disappearance of urine abnormalities. In
      addition, the MPO-ANCA titer and anti-GBM antibody titer of the patient decreased
      to within the normal range in one month and three months, respectively. Pulmonary
      lesions were not found throughout the course. Recently the emergence of anti-GBM
      antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA
      associated vasculitis has increasingly been reported. Accumulation of such cases
      may unravel the pathogenesis of these diseases. one month and three months,
      respectively. Pulmonary lesions were not found throughout the course. Recently
      the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in
      the course of MPO-ANCA-associated vasculitis has increasingly been reported.
      Accumulation of such cases may unravel the pathogenesis of these diseases.

PMID- 19601561
TI  - Quantitative studies of the interactions of metalloproteins with gold
      nanoparticles: identification of dominant properties of the protein that
      underlies the spectral changes.
AB  - The interaction of cytochrome C and a number of its components such as the apo
      protein, heme and a coordinated iron with gold nanospheres, has been
      investigated. The role of the heme group and its effect on the observed
      spectroscopic properties following binding of cytochrome C to the gold surface
      has been evaluated. Binding of the heme group directly to the gold is not
      observed, but the presence of the heme group and its effect on the interaction
      with the metal surface is shown to be influential. Other factors such as the
      metal oxidation state and the metal-free heme are also studied. A comparison to
      serum albumin binding as a nonmetallic protein provides further insight into the
      interaction characteristics.

PMID- 19601560
TI  - [Case of fibromuscular dysplasia revealed by the emergence of severe hypertension
      in the early phase of pregnancy].
AB  - A 25-year-old female at 10 weeks of her first pregnancy abruptly developed severe
      hypertension as high as 230/160 mmHg and thus was referred to our hospital. Her
      past history was unremarkable and no medication or supplement was prescribed. The
      laboratory findings revealed that plasma renin activity was 59.0 ng mL hr and
      plasma aldosterone concentration was 1700 pg mL together with serum creatinine of
      0.42 mg dL and serum potassium of 2.8 mEq L. Urinalysis revealed insignificant
      findings. Her hypertension was extremely resistant to antihypertensive agents,
      including hydralazine, alpha-methyldopa, and alpha beta blocker, leading to
      suspicion of secondary hypertension as a cause. Adrenal tumor was not detected
      but Doppler ultrasonography suggested the constriction of the right renal artery
      consistent with renovascular hypertension. Considering the following imaging test
      and medications, the patient and her family decided to abort the pregnancy. 3D-CT
      and MR angiography showed stenosis of the right renal artery, therefore,
      percutaneous transcatheter renal angioplasty was performed, resulting in
      normalization of the blood pressure without antihypertensives. Two years later
      she successfully gave birth uneventfully. Her hypertension was presumably
      irrelevant to preeclampsia because it occurred at 10 weeks of pregnancy and
      proteinuria was not associated. The stenosis of the right renal artery was
      probably due to fibromuscular dysplasia, which is one of the major causes of
      renal artery stenosis in young women. This patient was such a case and presented
      a difficult decision on how to treat and whether or not to abort. We will discuss
      the mechanism of hypertension in pregnancy and the advantages and disadvantages
      of available treatments for such cases.

PMID- 19601562
TI  - Stable amorphous cobalt nanoparticles formed by an in situ rapidly cooling
      microfluidic process.
AB  - The controlled synthesis of nanoparticles (NPs) with stable crystal structures
      and stable physical and chemical properties is a key issue for commercial
      applications. The use of a microfluidic reactor (MR) process has proven to be a
      flexible approach to control the fine crystal structures and the magnetic
      properties during the ripening and aging of the NPs. We have developed an in situ
      rapidly cooling microfluidic process (IRCMP) in which Co NPs with stable crystal
      structures and magnetic properties are synthesized by using elevated reaction
      temperatures followed by rapid quenching of the colloids to reduced temperatures.
      The Co NPs that are obtained by this process demonstrate stable crystal
      structures and stable magnetic properties for a much longer period of time (at
      least 3 months) than for Co NPs obtained by performing the reaction and the
      quenching processes at room temperature or under sonication.

PMID- 19601563
TI  - EXAFS and HRTEM evidence for As(III)-containing surface precipitates on
      nanocrystalline magnetite: implications for As sequestration.
AB  - Arsenic sorption onto iron oxide spinels such as magnetite could contribute to
      immobilization of arsenite (AsO3(3-)), the reduced, highly toxic form of arsenic
      in contaminated anoxic groundwaters, as well as to putative remediation
      processes. Nanocrystalline magnetite (<20 nm) is known to exhibit higher
      efficiency for arsenite sorption than larger particles, sorbing as much as
      approximately 20 micromol/m2 of arsenite. To improve our understanding of this
      process, we investigated the molecular level structure of As(III)-containing
      sorption products on two types of fine-grained magnetite: (1) a biogenic one with
      an average particle diameter of 34 nm produced by reduction of lepidocrocite
      (gamma-FeOOH) by Shewanella putrefaciens and (2) a synthetic, abiotic,
      nanocrystalline magnetite with an average particle diameter of 11 nm. Results
      from extended X-ray absorption spectroscopy (EXAFS) for both types of magnetite
      with As(III) surface coverages of up to 5 micromol/m2 indicate that As(III) forms
      dominantly inner-sphere, tridentate, hexanuclear, corner-sharing surface
      complexes (3C) in which AsO3 pyramids occupy vacant tetrahedral sites on
      octahedrally terminated {111} surfaces of magnetite. Formation of this type of
      surface complex results in a decrease in dissolved As(III) concentration below
      the maximum concentration level recommended by the World Health Organization (10
      microg/L), which corresponds to As(III) surface coverages of 0.16 and 0.19
      micromol/m2 in our experiments. In addition, high-resolution transmission
      electron microscopy (HRTEM) coupled with energy dispersive X-ray spectroscopy
      (EDXS) analyses revealed the occurrence of an amorphous As(III)-rich surface
      precipitate forming at As(III) surface coverages as low as 1.61 micromol/m2. This
      phase hosts the majority of adsorbed arsenite at surface coverages exceeding the
      theoretical maximum site density of vacant tetrahedral sites on the magnetite
      {111} surface (3.2 sites/nm2 or 5.3 micromol/m2). This finding helps to explain
      the exceptional As(III) sorption capacity of nanocrystalline magnetite particles
      (>10 micromol/m2). However, the higher solubility of the amorphous surface
      precipitate compared to the 3C surface complexes causes a dramatic increase of
      dissolved As concentration for coverages above 1.9 micromol/m2.

PMID- 19601564
TI  - Covalent layer-by-layer assembled superhydrophobic organic-inorganic hybrid
      films.
AB  - Using the concept of covalent layer-by-layer assembly (covalent LbL), used until
      now for the elaboration of films from polymers or dendrimers, we have constructed
      hybrid organic/inorganic surfaces by alternating different layers of amino
      functionalized silica nanoparticles (295 nm diameter) and epoxy-functionalized
      smaller silica nanoparticles (20 nm diameter). The so-realized macromolecular
      edifice leads to a hierarchical integration of nanoscale textures. Then
      hydrophobization of the last layer of amino-functionalized silica particles was
      carried out by grafting a new designed highly fluorinated aldehyde, creating a
      monomolecular layer via the formation of an imine function. Five highly
      fluorinated surfaces were built, and their water-repellent abilities were
      directly correlated to the surface topologies (i.e., the number of layers of
      silica nanoparticles and their organization on the glass support). The
      hydrophobicity increased with the number of layers and stable highly water
      repellent surfaces (static contact angle with water of 150+/-3 degrees and a
      contact angle hysteresis of 12 degrees) were obtained with the alternation of
      nine layers. This result demonstrates the possibility to construct covalent LbL
      edifices with functionalized silica nanoparticles of different sizes and open
      this field for the elaboration of responsive, sensing, and therapeutic surfaces
      with improved film stability.

PMID- 19601566
TI  - Layer-by-layer grafting of titanium phosphate onto mesoporous silica SBA-15
      surfaces: synthesis, characterization, and applications.
AB  - Metal phosphates have many applications in catalysis, separation, and proton
      conduction, but their small surface areas and/or constrained pore structures
      limit their utilization. Here, we report two new methods for the liquid-phase
      grafting of titanium phosphate onto mesoporous silica (SBA-15) surfaces: (1)
      alternate grafting of Ti(OPr(i))(4) and then POCl(3) and (2) one-pot grafting of
      titanium phosphate formed in situ by employing Ti(OPr(i))(4) (a base) and POCl(3)
      (an acid) as an appropriate "acid-base pair". Both the size of mesopores and the
      content of titanium phosphate can be changed by increasing the number of
      modification cycles in a stepwise (or layer-by-layer) fashion. The obtained
      products were characterized by inductively coupled plasma optical emission
      spectroscopy, X-ray diffraction, N(2) adsorption-desorption, transmission
      electron microscopy, (31)P and (29)Si magic-angle spinning NMR, and NH(3)
      temperature-programmed desorption, and their performance in acid catalysis and
      metal ion adsorption was investigated. This work provides new methodologies for
      the general synthesis of supported metal phosphates with large surface areas,
      ordered nanoporous structures, and acid properties.

PMID- 19601565
TI  - Direct biophotolithographic method for generating substrates with multiple
      overlapping biomolecular patterns and gradients.
AB  - We describe an approach to generate multicomponent surface-immobilized patterns
      and gradients on the basis of the photochemically controlled covalent coupling of
      solution-phase biomolecules to benzophenone-modified substrates. Gradients were
      simply achieved by continuously varying the exposure to nondamaging UV light
      across the surface with the gradient profile controlled by biomolecule
      concentration and the spatial and temporal illumination of the surface.
      Sequential exposure of the same surface in the presence of different biomolecules
      resulted in overlapping patterns and gradients of proteins and carbohydrates.
      Finally, we preliminarily demonstrate that the resulting surfaces are suitable
      for generating model substrates to probe cell-substrate interactions.

PMID- 19601567
TI  - Nanoscale multiple gaseous layers on a hydrophobic surface.
AB  - The nanoscale gas state at the interfaces of liquids (water, acid, and salt
      solutions) and highly oriented pyrolytic graphite (HOPG) was investigated via
      tapping-mode atomic force microscopy (AFM). For the first time, we report that
      the interfacial gases could form bilayers and trilayers, i.e., on the top of a
      flat gas layer, there are one or two more gas layers. The formation of these gas
      layers could be induced by a local supersaturation of gases, which can be
      achieved by (1) temperature difference between the liquids and the HOPG
      substrates or (2) exchange ethanol with water. Furthermore, we found that the gas
      layers were less stable than spherical bubbles. They could transform to bubbles
      with time or under the perturbation of the AFM tip.

PMID- 19601568
TI  - Vibrational and electronic characterization of ethynyl derivatives grafted onto
      hydrogenated Si(111) surfaces.
AB  - Covalent grafting of ethynyl derivatives (-C triple bond C-H, -C triple bond C
      CH3, -C triple bond C-aryl) onto H-terminated Si(111) surfaces was performed by a
      one-step anodic treatment in Grignard electrolytes. The electrochemical grafting
      of such ethynyl derivatives, which tends to form ultrathin polymeric layers, can
      be controlled by the current and charge flow passing through the Si electrode.
      The prepared ultrathin layers cover the Si surface and had a thickness up to 20
      nm, as investigated by the scanning electron microscopy (SEM) technique.
      Exchanging Cl for Br in the ethynyl Grignard reagent leads to very thin layers,
      even under the same electrochemical conditions. However, for all ethynyl
      derivatives, high-resolution synchrotron X-ray photoelectron spectroscopy (SXPS)
      investigations reveal the incorporation of halogen atoms in the organic layers
      obtained. Moreover, it was observed that the larger the end group of the ethynyl
      derivative, the thinner the thickness of the ultrathin polymeric layers as
      measured by both SXPS and SEM techniques after low and high current flow
      respectively. For the first time, these new types of ultrathin organic layers on
      Si surfaces were investigated using infrared spectroscopic ellipsometry (IRSE).
      The different possible reaction pathways are discussed.

PMID- 19601569
TI  - Nonsynchronous change in the head and tail of dioctadecyldimethylammonium bromide
      molecules during the liquid crystalline to coagel phase transformation process.
AB  - Dioctadecyldimethylammonium bromide (DODAB) is known to self-assemble into
      several lamellar structures in water, existing as either liquid crystalline, gel,
      or coagel phases. In this work, by using differential scanning calorimetry,
      Fourier transform infrared spectroscopy, and X-ray diffraction techniques, we
      have characterized the details of the phase transition mechanisms of the DODAB
      aqueous dispersions. It was found that the liquid crystalline converts to the
      coagel phase via a two-step mechanism: first to the gel phase upon cooling and
      then to the stable coagel phase. Although significant conformational changes in
      the hydrocarbon tails were observed in both steps, changes in the headgroups of
      DODAB were only detected in the second step. More interestingly, we found that
      the lipid tails change prior to the headgroups during the overall liquid
      crystalline to coagel phase transformation process. This is regarded as a
      nonsynchronicity phenomenon, which reflects the regional (head/tail) imbalance in
      molecular interactions. Such a nonsynchronicity phenomenon in the self-assembled
      aggregates composed of the medium-sized DODAB molecules will shed light on our
      understanding of the polymorphism and reversibility of amphiphiles including both
      surfactants and biomembrane phospholipids.

PMID- 19601570
TI  - Kinetic resolution of rac-1-phenylethanol with immobilized lipases: a critical
      comparison of microwave and conventional heating protocols.
AB  - The lipase-catalyzed kinetic resolution of rac-1-phenylethanol with vinyl acetate
      as acyl donor and cyclohexane as solvent has been investigated applying both
      microwave dielectric heating and conventional thermal heating in order to probe
      the existence of nonthermal microwave effects. All transformations were conducted
      at 40 degrees C in a dedicated reactor setup that allowed accurate internal
      reaction temperature measurements with use of fiber-optic probes. Quartz reaction
      vessels that allow higher levels of microwave power to be administered to the
      reaction mixture were used for all experiments. For all five studied immobilized
      lipases, the observed reactivities and enantioselectivities in microwave and oil
      bath experiments were identical and thus not related to the presence of the
      microwave field. The effect of magnetic stirring proved critical as too rapid
      stirring in some instances destroyed the enzyme support structure and led to
      altered reactivities and selectivities.

PMID- 19601571
TI  - Diastereoselective synthesis of a spironoraristeromycin using an acylnitroso
      Diels-Alder reaction.
AB  - The tert-butyl N-hydroxycarbamate-derived nitroso reagent 1 reacted with N-Cbz
      protected spirocyclic diene 2 to provide spirocycloadduct 3. Here we describe the
      efficient conversion of 3 into the novel carbocyclic nucleoside
      spironoraristeromycin 4.

PMID- 19601572
TI  - Enantiodiscrimination of flexible cyclic solutes using NMR spectroscopy in
      polypeptide chiral mesophases: investigation of cis-decalin and THF.
AB  - The conformational dynamics and orientational behavior of two model cyclic
      molecules, cis-decalin (cis-dec) and tetrahydrofurane (THF), dissolved in weakly
      ordering, polypeptidic chiral liquid crystals (CLCs) are theoretically discussed
      and experimentally investigated using deuterium and carbon-13 NMR spectroscopies.
      The analysis of enantiomeric and enantiotopic discriminations in these compounds
      is shown to depend on the rate of conformational exchange regime, slow or fast.
      The slow exchange regime is illustrated through the case of cis-dec at low
      temperature (243 K). We show that the deuterium NMR spectra in this regime can be
      qualitatively and quantitatively interpreted by restricting the conformational
      pathway of cis-dec to two enantiomeric conformers of C(2)-symmetry. The
      orientational order parameters of these interconverting enantiomers are
      calculated by matching the (2)H quadrupolar splittings with calculated conformer
      structures. The fast exchange regime is investigated through the examples of cis
      dec at high temperature (356 K) and THF at room temperature (300 K). The (2)H NMR
      spectra above the coalescence temperature are analyzed by introducing the concept
      of "average molecular structure". This fictitious structure allows easily
      identifying NMR equivalences of solutes dissolved in CLC. However, it cannot be
      applied to determine consistent orientational order parameters. This study
      emphasizes that enantiotopic discriminations observed for flexible molecules in
      the fast exchange regime can be quantitatively interpreted only by considering
      the orientational order of each conformer.

PMID- 19601573
TI  - Colloidal stability influenced by inhomogeneous surfactant assemblies in confined
      spaces.
AB  - Recently, a molecular-level self-consistent field approach was used to show that
      some surfactants assemblies (with local cylindrical structure) can bridge between
      two surfaces that in turn are covered by surfactant bilayers. The stability of
      such a connection is related to a higher end-cap (free) energy of the worm-like
      micelle (in solution) than the connection (free) energy of the micelle with the
      surface layer. This preliminary study has been extended here to know the
      viability of this connection as a function of different parameters related to the
      surfactant structure and the interaction between the surfaces and the different
      moieties composing the surfactant. The effect of such parameters on the structure
      of the connection, the thermodynamic stability of such a formation, and the
      interaction curve between such surfaces has been analyzed in case the connection
      was possible. A secondary minimum has been found, which could give rise to
      surfactant-induced flocculation. This minimum is strongly affected by the
      surfactant properties. Other interesting surfactant structures have been
      predicted to form in confined spaces under certain parameter regimes.

PMID- 19601574
TI  - Thermo-induced aggregation behavior of poly(ethylene oxide)-b-poly(N
      isopropylacrylamide) block copolymers in the presence of cationic surfactants.
AB  - Low-molecular-weight cationic surfactants, dodecyltrimethylammonium bromide
      (DTAB) and cetyltrimethylammonium bromide (CTAB), were introduced to dilute
      aqueous solutions of thermosensitive poly(ethylene oxide)-b-poly(N
      isopropylacrylamide) (PEO-b-PNIPAM) block copolymers at concentrations (C(s))
      either lower or higher than the critical micelle concentrations (cmc) of the
      surfactants. The copolymer/surfactant mixtures were investigated by dynamic and
      static light scattering at different temperatures. At temperature lower than the
      aggregation temperature (T(agg)), the disaggregation of the copolymers from the
      loose associations was observed upon addition of the surfactants(.) The thermo
      induced aggregation behavior was found to be profoundly influenced with the
      cooperation of cationic surfactants in terms of T(agg) and the structural
      characteristics of the aggregates formed at high temperature. In general, T(agg)
      was increased together with the decrease in the size and molecular weight of the
      aggregates. These were attributed to the copolymer/surfactant interactions and
      the electrostatic repulsion coming from the ionic head groups of the surfactants
      within the mixed aggregates. These changes were much more pronounced at higher
      C(s). CTAB, which has a longer hydrophobic tail, displayed higher influences
      compared to DTAB. The formation of vesicles, by one of the copolymers, was
      suppressed in the presence of CTAB. At the higher CTAB concentration, only small
      mixed aggregates with very low mass were observed even at the highest temperature
      investigated.

PMID- 19601576
TI  - Asymmetric synthesis of (+)-polyanthellin A.
AB  - A concise and convergent route to (+)-polyanthellin A is presented. This
      synthesis features a diastereoselective cyclopropane/aldehyde [3+2] cycloaddition
      to install the hydroisobenzofuran core. The use of MADNTf(2) as a potent, bulky
      Lewis acid was essential to allow a labile beta-silyloxy aldehyde to be used in
      the cycloaddition. Other key steps include a ring-closing metathesis and a
      selective olefin oxidation.

PMID- 19601575
TI  - Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core
      promoter with implications for inhibition of telomerase by G-quadruplex
      interactive ligands.
AB  - The hTERT core promoter contains a G-rich region of 12 consecutive G-tracts,
      embracing 3 Sp1 binding sites, and has the potential to form multiple G
      quadruplexes. From the 12 runs of guanines, 9 putative hTERT G-quadruplex-forming
      sequences were selected to assay for G-quadruplex formation and stability using
      circular dichroism and a Taq polymerase stop assay. Results from biophysical and
      chemical assays demonstrate an approximate inverse correlation between total loop
      size and structure stability. Investigation of the full-length hTERT G-rich
      sequence using a Taq polymerase stop assay and dimethyl sulfate footprinting
      revealed the formation of a unique end-to-end stacked G-quadruplex structure from
      this sequence. This structure consists of an all parallel G-quadruplex, formed by
      four consecutive G-tracts, linked to another, atypical G-quadruplex, formed by
      two pairs of consecutive G-tracts separated by a 26-base loop. This 26-base loop
      likely forms a stable hairpin structure, which would explain the unexpected
      stability of this G-quadruplex. Significantly, the formation of this tandem G
      quadruplex structure in the full-length sequence masks all three Sp1 binding
      sites, which is predicted to produce significant inhibition of hTERT promoter
      activity. Furthermore, our study implies that inhibition of telomerase activity
      by some G-quadruplex ligands is not only produced by targeting telomeric G
      quadruplexes but also by stabilization of the hTERT promoter G-quadruplexes.

PMID- 19601577
TI  - Thiosemicarbazones from the old to new: iron chelators that are more than just
      ribonucleotide reductase inhibitors.

PMID- 19601578
TI  - X-ray crystal structure of human heme oxygenase-1 with (2R,4S)-2-[2-(4
      chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2
      yl)thio)methyl]-1,3-dioxolane: a novel, inducible binding mode.
AB  - The crystal structure of human heme oxygenase-1 (HO-1) in complex with (2R,4S)-2
      [2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5
      trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane (4) reveals a novel,
      inducible binding mode. Inhibitor 4 coordinates the heme iron, with its
      chlorophenyl group bound in a distal hydrophobic pocket, as seen in previous
      structures. However, accommodation of the 5-trifluoromethylpyridin-2-yl group
      requires a significant shift in the proximal helix, inducing the formation of a
      hydrophobic pocket. This is the first example of an induced binding pocket
      observed in HO-1.

PMID- 19601579
TI  - Oxidation of the dihydrochalcone aspalathin leads to dimerization.
AB  - Aspalathin and nothofagin are typical ingredients of unfermented rooibos
      (Krafczyk, N.; Glomb, M. A. J. Agric. Food Chem. 2008, 56, 3368). During
      oxidation these dihydrochalcones were degraded to higher molecular weight
      browning products under aerated and nonenzymatic conditions. In the early stages
      of browning reactions aspalathin formed two dimers. These two compounds were
      unequivocally established as atropisomers stemming from oxidative A to B ring
      coupling. Multilayer countercurrent chromatography (MLCCC) and preparative high
      performance liquid chromatography (HPLC) were applied to obtain pure substances.
      The purity and identity of isolated dimers were confirmed by different NMR
      experiments, HPLC-DAD-MS, and HR-MS. In parallel to the formation of chromophores
      during the fermentation of black tea, the formation of aspalathin dimers implies
      an important mechanistic channel for the generation of color during the
      processing of rooibos.

PMID- 19601580
TI  - Three-component assembly of amines, boronic acids, and a polyfunctionalized
      furanose: a concise entry to furanose-based carbohydrate templates.
AB  - A highly functionalyzed furanose derivative, accessible in five steps from D
      mannose, comprising a halo-alkenyl allylic-oxirane system, undergoes a palladium
      catalyzed one-pot, three component, assembly with boronic acids (or alkyl
      boranes) and amines to give, in a complete regio- and stereocontrolled manner, a
      sugar based derivative with two sites of molecular diversity.

PMID- 19601581
TI  - Luminescent metal complexes within polyelectrolyte layers: tuning electron and
      energy transfer.
AB  - The electrochemical and photophysical properties of a luminescent metal center,
      [Os(bpy)(3)](2+), are significantly modified by encapsulation within a conducting
      polymer composite film. Cyclic voltammetry reveals that the encapsulation in an
      inherently conducting polymer, polyaniline (Pani) or polypyrrole (PPy), can
      dramatically influence the charge-transfer rates between the metal centers. The
      increased electron transport, most likely mediated through the conducting polymer
      backbone, significantly enhances the electrochemiluminescence (ECL) efficiency.
      The increased communication between adjacent metal centers can also result in
      other interesting properties, such as photoinduced electron-transfer processes.
      In situ electron spin resonance (ESR) spectroscopy has been used to probe the
      photo-oxidation of an osmium metal center encapsulated in a PPy composite film.
      The irradiation of PPy in the presence of the osmium metal center resulted in the
      photo-oxidation of the Os(2+) to Os(3+) state and the consequent reduction of the
      PPy polyelectrolyte. The degree of communication between luminescent metal
      centers allows the composite properties to be tuned for various applications
      including ECL sensor devices and light-switching and light-harvesting systems.

PMID- 19601582
TI  - Design of a novel heme protein with a non-heme globin scaffold.
AB  - A binding site for iron protoporphyrin IX (heme) was designed and embedded in a
      photosynthetic non-heme protein, phycocyanin, which forms a globin-like backbone
      structure, called a globin fold, but lacks sequence similarity to the globin
      family containing myoglobins and hemoglobins. Based on the structural alignment
      of the phycocyanin and myoglobin molecules, the proximal and distal His residues
      were repositioned in the phycocyanin sequence for heme ligation. The heme-binding
      pocket was created around the His residues by several residue replacements in the
      phycocyanin core. The synthesized phycocyanin variant, designated as HPY, bound
      one heme per protein molecule and showed spectroscopic features characteristic of
      six-coordinated heme proteins. The heme-binding HPY exhibited redox activity with
      an electrochemical midpoint potential of -130 mV against the standard hydrogen
      electrode, which was approximately 200 mV lower than the potential of natural
      myoglobins but 50 mV higher than the typical values of designed heme proteins
      with four-helix bundle or globin scaffolds. HPY also displayed native-like
      folding properties, in contrast to these designed heme proteins. However, the
      bound ferrous heme of HPY was quickly reoxidized by air and did not stably bind
      O(2), unlike the natural globins. The present results demonstrated that the
      globin fold of a non-globin protein is suitable for binding heme but is not
      sufficient for the reversible O(2) binding and myoglobin functions. The
      comparison of HPY with the natural globins may yield new insights into the
      essential features for realizing the natural heme protein functions.

PMID- 19601583
TI  - The photochemical C2-C6 cyclization of enyne-allenes: interception of the fulvene
      diradical with a radical clock ring opening.
AB  - The mechanism of the photochemical C(2)-C(6) cyclization of enyne-allenes has
      been studied through radical clock, intramolecular kinetic isotope effect, and
      laser flash photolysis (LFP) experiments as well as density functional theory
      (DFT) and ab initio computations. While the photochemical cyclization of enyne
      allenes 1 and 2 furnished ene and Diels-Alder products without any cyclopropyl
      ring opening, that of 3 carrying the ultrafast diphenylcyclopropylcarbinyl
      radical clock afforded products derived from cyclopropyl ring opening. Laser
      flash photolysis (LFP) studies on enyne-allene 3 point to an allene triplet
      excited state (transient A) as a primarily formed short-lived (tau = 430 ns)
      intermediate. In addition, we have obtained evidence for the formation of a
      diphenylmethyl-type diradical (transient C, tau = 1.0 micros) resulting from ring
      opening of a diphenylcyclopropane ring. C subsequently undergoes a surprisingly
      slow (tau = 1.0 micros) 1,6-hydrogen shift leading to the stable 1,3-diene 6.

PMID- 19601585
TI  - Mechanistic investigations of the reaction of an iron(III) octa-anionic porphyrin
      complex with hydrogen peroxide and the catalyzed oxidation of diammonium-2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonate).
AB  - A detailed study of the effect of pH, temperature, and pressure on the reaction
      of hydrogen peroxide with [Fe(III)(P(8-))](7-), where P(8-) represents the octa
      anionic porphyrin, was performed using stopped-flow techniques. Depending on the
      pH, different high valent iron-oxo species were formed. At pH < 9 formation of a
      two-electron oxidized species [(porphyrin(+*))Fe(IV)=O] was observed. In
      contrast, at pH > 9 only the one electron oxidized species [(porphyrin)Fe(IV)=O]
      was found to be present in solution. Under selected conditions at pH 8 it was
      possible to determine rate constants for both the coordination of hydrogen
      peroxide and subsequent heterolytic cleavage of the O-O bond. At pH 11 a
      composite rate constant for coordination of H(2)O(2) and homolytic cleavage of
      the O-O bond could be measured. In addition, it was possible to determine the
      activation parameters for the overall reaction sequence leading to the formation
      of [(porphyrin)Fe(IV)=O]. Careful analysis of the obtained data supports an
      associatively activated mechanism for the coordination of hydrogen peroxide. The
      catalytic properties of [Fe(III)(P(8-))](7-) in the presence of H(2)O(2) were
      also investigated. Both high valent iron-oxo species turned out to be able to
      oxidize diammonium-2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) to
      the radical cation ABTS(+*). At higher hydrogen peroxide concentrations a reduced
      yield of ABTS(+*) was observed because of increased catalase activity of
      [Fe(III)(P(8-))](7-). At high pH disproportionation of ABTS(+*) to ABTS and
      ABTS(2+) occurred, which could be suppressed by an excess of unreacted ABTS. In
      slightly basic to acidic solutions this reaction did not play a role.

PMID- 19601586
TI  - Biomimetic model featuring the NH proton and bridging hydride related to a
      proposed intermediate in enzymatic H(2) production by Fe-only hydrogenase.
AB  - Iron azadithiolate phosphine-substituted complex and its protonated species
      featuring the NH proton and/or bridging Fe hydride, [Fe(2)(mu
      S(CH(2))(2)N(n)Pr(H)(m)(CH(2))(2)S)(mu-H)(n)(CO)(4)(PMe(3))(2)](2)((2m+2n)+) (1,
      m = n = 0; [1-2H(N)](2+), m = 1, n = 0; [1-2H(N)2H(Fe)](4+), m = n = 1), are
      prepared to mimic the active site of Fe-only hydrogenase. X-ray crystallographic
      analyses of these three complexes reveal that two diiron subunits are linked by
      two azadiethylenethiolate bridges to construct a dimer-of-dimer structure. (31)P
      NMR spectroscopy confirms two trimethylphosphine ligands within the diiron moiety
      are arranged in the apical/basal configuration, which is consistent with the
      solid-state structural characterization. Deprotonation of the NH proton in [1
      2H(N)](2+) and [1-2H(N)2H(Fe)](4+) occurs in the presence of triethanolamine
      (TEOA), which generates 1 and [1-2H(Fe)](2+), respectively. Deprotonation of the
      Fe hydride is accomplished by addition of bistriphenylphosphineimminium chloride
      ([PPN]Cl). It is observed that the Fe hydride species, [1-2H(Fe)](2+), is a
      kinetic product which converts to its thermodynamically stable tautomer, [1
      2H(N)](2+), in solution, as evidenced by IR and NMR spectroscopy. The pK(a)
      values of the aza nitrogen and the diiron sites are estimated to be 8.9-15.9 and
      <8.9, respectively. [1-2H(N)2H(Fe)](4+) has been observed to evolve H(2)
      electrocatalytically at a mild potential (-1.42 V vs Fc/Fc(+)) in CH(3)CN
      solution. Catalysis of [1-2H(N)2H(Fe)](4+) is found to be as efficient as that of
      the related diiron azadithiolate complexes. In the absence of a proton source, [1
      2H(N)2H(Fe)](4+) undergoes four irreversible reduction processes at -1.26, -1.42,
      -1.82, and -2.43 V, which are attributed to the reduction events from [1
      2H(N)2H(Fe)](4+), [1-2H(Fe)](2+), [1-2H(N)](2+), and 1, respectively, according
      to bulk electrolysis and voltammetry in combination of titration experiments with
      acids.

PMID- 19601587
TI  - Closo versus hypercloso metallaboranes: A DFT study.
AB  - The structures and electronic relationship of 9-, 10-, 11-, and 12-vertex closo
      and hypercloso (isocloso) metallaboranes are explored using DFT calculations. The
      role of the transition metal in stabilizing the hypercloso borane structures is
      explained using the concept of orbital compatibility. The hypercloso structures,
      C(6)H(6)MB(n-1)H(n-1) (n = 9-12; M = Fe, Ru, and Os) are taken as model
      complexes. Calculations on metal free polyhedral borane B(n)H(n) suggest that n
      vertex hypercloso structures need only n skeleton electron pairs (SEPs), but the
      structure will have one or more six-degree vertices, whereas the corresponding
      closo structures with n + 1 SEPs have only four- and five-degree vertices. This
      high-degree vertex of hypercloso structures can be effectively occupied by
      transition metal fragments with their highly diffused orbitals. Calculations
      further show that a heavy transition metal with more diffused orbitals prefers
      over a light transition metal to form hypercloso geometry. This is in accordance
      with the fact that there are more experimentally characterized hypercloso
      structures with the heavy transition metals. The size of the exohedral ligands
      attached to the metal atom also plays a role in deciding the stability of the
      hypercloso structure. The interaction between the borane and the metal fragments
      in the hypercloso geometry is analyzed using the fragment molecular orbital
      approach. The interconversion of the closo and hypercloso structures by the
      addition and removal of the electrons is also discussed in terms of the
      correlation diagrams.

PMID- 19601588
TI  - Influence of the cobalt particle size in the CO hydrogenation reaction studied by
      in situ X-ray absorption spectroscopy.
AB  - The influence of particle size in the carbon monoxide hydrogenation reaction has
      been studied using cobalt nanoparticles (NPs) with narrow size distribution
      prepared from colloidal chemistry. The surfactant covering the NPs after
      synthesis could be removed by heating to 200-270 degrees C in H(2). Soft X-ray
      absorption spectroscopy was performed using a gas flow cell under reaction
      conditions of H(2) and CO at atmospheric pressure. Flow of pure hydrogen at 350
      degrees C removed the protecting surfactant layer and reduced the NPs from
      oxidized to metallic. The NPs remained metallic during the methanation reaction
      with their surface covered by CO. The methanation turnover frequency of silica
      supported NPs was found to decrease with diameter below 10 nm, whereas the
      reaction activation energy was found to be independent of NP size. H-D exchange
      experiments indicated that it is the dissociation of H(2) that is responsible for
      the observed decrease in activity with size.

PMID- 19601584
TI  - Structure and function of the influenza A M2 proton channel.
AB  - The M2 protein of influenza A viruses forms a tetrameric pH-activated proton
      selective channel that is targeted by the amantadine class of antiviral drugs.
      Its ion channel function has been extensively studied by electrophysiology and
      mutagenesis; however, the molecular mechanism of proton transport is still
      elusive, and the mechanism of inhibition by amantadine is controversial. We
      review the functional data on proton channel activity, molecular dynamics
      simulations of the proton conduction mechanism, and high-resolution structural
      and dynamical information of this membrane protein in lipid bilayers and lipid
      mimetic detergents. These studies indicate that elucidation of the structural
      basis of M2 channel activity and inhibition requires thorough examination of the
      complex dynamics and conformational plasticity of the protein in different lipid
      bilayers and lipid-mimetic environments.

PMID- 19601589
TI  - Different role of the Jalpha helix in the light-induced activation of the LOV2
      domains in various phototropins.
AB  - Phototropins (phot) are blue light receptors in plants which are involved in
      phototropism, stomatal opening, and chloroplast movements. Phototropin has two
      LOV domains (LOV1 and LOV2), and the LOV2 domain is responsible for activation of
      Ser/Thr kinase. There is an alpha-helix at the C-terminal side of the LOV2
      domain, which is called the Jalpha helix. The functional importance of the Jalpha
      helix has been established for Arabidopsis phot1, where light-induced structural
      perturbation takes place in the Jalpha helix during the photocycle of LOV2
      domains. However, the present FTIR study reports a different role of the Jalpha
      helix in light-induced signal transduction of LOV2 domains. Here we construct
      LOV2 domains with (LOV-Jalpha) and without (LOV-core) the Jalpha helix for
      Arabidopsis phot1 and phot2 and Adiantum neochrome 1 and compare their light
      induced difference FTIR spectra. Light-induced protein structural changes differ
      significantly between LOV-Jalpha and LOV-core for Arabidopsis phot1 [Yamamoto,
      A., Iwata, T., Sato, Y., Matsuoka, D., Tokutomi, S., and Kandori, H. (2009)
      Biophys. J. 96, 2771-2778]. In contrast, the difference spectra are identical
      between LOV-Jalpha and LOV-core for Adiantum neochrome 1. In Arabidopsis phot2,
      the protein structural changes are intermediate between Arabidopsis phot1 and
      Adiantum neochrome 1. These results suggest that the conformational changes of
      the Jalpha helix and the interaction between the LOV-core and the Jalpha helix
      are different among phototropins. The role of the Jalpha helix for signal
      transduction in phototropins is discussed.

PMID- 19601590
TI  - Kinetic and thermodynamic stability of the group 13 trihydrides.
AB  - The kinetic and thermodynamic stabilities of the group 13 hydrides EH(3) (E = B,
      Al, Ga, In, Tl, E113) are investigated by relativistic density functional and
      wave function based theories. The unimolecular decomposition of EH(3) --> EH +
      H(2) becomes energetically more favorable going down the Group 13 elements, with
      the H(2)-abstraction of InH(3), TlH(3), and (E113)H(3) (E113: element with
      nuclear charge 113) being exothermic. In accordance with the Hammond-Leffler
      postulate, the activation barrier for the dissociation process decreases
      accordingly going down the group 13 elements in the periodic table shifting to an
      early transition state, with activation energies ranging from 88.4 kcal/mol for
      BH(3) to 41.3 kcal/mol for TlH(3) and only 21.6 kcal/mol for (E113)H(3) at the
      scalar relativistic coupled cluster level of theory. For both TlH(3) and
      (E113)H(3) we investigated spin-orbit effects using Dirac-Hartree-Fock and second
      order Moller-Plesset theory to account for electron correlation. For (E113)H,
      spin-orbit coupling results in a chemically inert closed 7p(1/2)-shell, thus
      reducing the stability of the higher oxidation state even further. We also
      investigated the known organothallium compound Tl(CH(3))(3), which is
      thermodynamically unstable similar to TlH(3), but kinetically very stable with an
      activation barrier of 57.1 kcal/mol.

PMID- 19601591
TI  - Reaction dynamics of O((1)D,(3)P) + OCS studied with time-resolved Fourier
      transform infrared spectroscopy and quantum chemical calculations.
AB  - Time-resolved infrared emission of CO(2) and OCS was observed in reactions
      O((3)P) + OCS and O((1)D) + OCS with a step-scan Fourier transform spectrometer.
      The CO(2) emission involves Deltanu(3) = -1 transitions from highly vibrationally
      excited states, whereas emission of OCS is mainly from the transition (0, 0
      degrees , 1) --> (0, 0 degrees , 0); the latter derives its energy via near
      resonant V-V energy transfer from highly excited CO(2). Rotationally resolved
      emission lines of CO (v <or= 4 and J <or= 30) were also observed in the reaction
      O((1)D) + OCS. For O((3)P) + OCS, weak emission of CO(2) diminishes when Ar is
      added, indicating that O((3)P) is translationally hot to overcome the barrier for
      CO(2) formation. The band contour of CO(2) agrees with a band shape simulated on
      the basis of a Dunham expansion model of CO(2); the average vibrational energy of
      CO(2) in this channel is 49% of the available energy. This vibrational
      distribution fits with that estimated through a statistical partitioning of
      energy E* congruent with 18,000 +/- 500 cm(-1) into all vibrational modes of
      CO(2). For the reaction of O((1)D) + OCS, approximately 51% of the available
      energy is converted into vibrational energy of CO(2), and a statistical
      prediction using E* congruent with 30,000 +/- 500 cm(-1) best fits the data. The
      mechanisms of these reactions are also investigated with the CCSD(T)/6
      311+G(3df)//B3LYP/6-311+G(3df) method. The results indicate that the triplet
      O((3)P) + OCS(X(1)Sigma(+)) surface proceeds via direct abstraction and
      substitution channels with barriers of 27.6 and 36.4 kJ mol(-1), respectively, to
      produce SO(X(3)Sigma(-)) + CO(X(1)Sigma(+)) and S((3)P) + CO(2)(X(1)A(1)),
      whereas two intermediates, OSCO and SC(O)O, are formed from the singlet O((1)D) +
      OCS(X(1)Sigma(+)) surface without barrier, followed by decomposition to
      SO(a(1)Delta) + CO(X(1)Sigma(+)) and S((1)D) + CO(2)(X(1)A(1)), respectively. For
      the ground-state reaction O((3)P) + OCS(X(1)Sigma(+)), the singlet-triplet curve
      crossings play important roles in the observed kinetics and chemiluminescence.

PMID- 19601592
TI  - Kinetics of bromine-magnesium exchange reactions in heteroaryl bromides.
AB  - Competition experiments are reported which compare the relative reactivities of
      bromoheteroarenes toward i-PrMgCl x LiCl in THF at 0 degrees C.

PMID- 19601595
TI  - Polarized luminescence of non-mesogenic europium(III) complexes doped into a
      nematic liquid crystal.
AB  - The luminescence spectra of europium(III) complexes dissolved in the liquid
      crystal 4'-pentyl-4-cyanobiphenyl (5CB) were investigated. Upon alignment of the
      europium(III)-doped nematic liquid-crystal host in a liquid-crystal cell with
      alignment layers, polarization effects were observed in the emission spectra.
      These polarization effects were visible as differences in the relative
      intensities of the crystal-field components of the transitions. Although the
      europium(III) complexes do not need to be liquid-crystalline themselves, some
      structural anisotropy is required for good alignment in the liquid crystal host
      and for the generation of linearly polarized light.

PMID- 19601593
TI  - Ternary complexes of iron, amyloid-beta, and nitrilotriacetic acid: binding
      affinities, redox properties, and relevance to iron-induced oxidative stress in
      Alzheimer's disease.
AB  - The interaction of amyloid-beta (Abeta) and redox-active metals, two important
      biomarkers present in the senile plaques of Alzheimer's disease (AD) brain, has
      been suggested to enhance the Abeta aggregation or facilitate the generation of
      reactive oxygen species (ROS). This study investigates the nature of the
      interaction between the metal-binding domain of Abeta, viz., Abeta(1-16), and the
      Fe(III) or Fe(II) complex with nitrilotriacetic acid (NTA). Using electrospray
      ionization mass spectrometry (ESI-MS), the formation of a ternary complex of
      Abeta(1-16), Fe(III), and NTA with a stoichiometry of 1:1:1 was identified. MS
      also revealed that the NTA moiety can be detached via collision-induced
      dissociation. The cumulative dissociation constants of both Abeta-Fe(III)-NTA and
      Abeta-Fe(II)-NTA complexes were deduced to be 6.3 x 10(-21) and 5.0 x 10(-12)
      M(2), respectively, via measurement of the fluorescence quenching of the sole
      tyrosine residue on Abeta upon formation of the complex. The redox properties of
      these two complexes were investigated by cyclic voltammetry. The redox potential
      of the Abeta-Fe(III)-NTA complex was found to be 0.03 V versus Ag/AgCl, which is
      negatively shifted by 0.54 V when compared to the redox potential of free
      Fe(III)/Fe(II). Despite such a large potential modulation, the redox potential of
      the Abeta-Fe(III)-NTA complex is still sufficiently high for a range of redox
      reactions with cellular species to occur. The Abeta-Fe(II)-NTA complex
      electrogenerated from the Abeta-Fe(III)-NTA complex was also found to catalyze
      the reduction of oxygen to produce H(2)O(2). These findings provide significant
      insight into the role of iron and Abeta in the development of AD. The binding of
      iron by Abeta modulates the redox potential to a level at which its redox cycling
      occurs. In the presence of a biological reductant (antioxidant), redox cycling of
      iron could disrupt the redox balance within the cellular milieu. As a
      consequence, not only is ROS continuously produced, but oxygen and biological
      reductants can also be depleted. A cascade of biological processes can therefore
      be affected. In addition, the strong binding affinity of Abeta toward Fe(III) and
      Fe(II) indicates Abeta could compete for iron against other iron-containing
      proteins. In particular, its strong affinity for Fe(II), which is 8 orders of
      magnitude stronger than that of transferrin, would greatly interfere with iron
      homeostasis.

PMID- 19601594
TI  - New arylthioindoles and related bioisosteres at the sulfur bridging group. 4.
      Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling
      studies.
AB  - New arylthioindoles along with the corresponding ketone and methylene compounds
      were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells,
      sulfur derivatives were superior or sometimes equivalent to the ketones, while
      methylene derivatives were substantially less effective. Esters 24, 27-29, 36,
      39, and 41 showed approximately 50% of inhibition on human HeLa and HCT116/chr3
      cells at 0.5 microM, and these compounds inhibited the growth of HEK, M14, and
      U937 cells with IC(50)'s in the 78-220 nM range. While murine macrophage J744.1
      cell growth was significantly less affected (20% at higher concentrations), four
      other nontransformed cell lines remained sensitive to these esters. The effect of
      drug treatment on cell morphology was examined by time-lapse microscopy. In a
      protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild
      type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39
      also showed significant inhibition.

PMID- 19601596
TI  - Model of autocrine/paracrine signaling in epithelial layer: geometrical
      regulation of intercellular communication.
AB  - An autocrine/paracrine signaling model in epithelial layers is described. The
      axially symmetric model of the epithelial layer explicitly considers the
      microvilli of the epithelial cells and the gaps between nearest neighbor
      microvilli. Ligand trapping site distribution functions and probability of
      autocrine signaling are calculated for different epithelial geometries and ligand
      sources by numerically solving the inhomogeneous stationary diffusion equation,
      the Poisson equation. In general, the global characteristics of the trapping site
      distribution curves are similar to the ones obtained for a planar epithelial
      model, and the superimposed small periodical changes of the curves reflect the
      details of the epithelial geometry. However, when ligands are emitted into a
      narrow gap between nearest neighbor microvilli the probability of local trapping
      is particularly high, causing a locally large deviation from the overall behavior
      of the trapping site distribution curves. If the microvilli of the cell are
      closely packed, then the probability of paracrine signaling is about 0.2.
      However, this probability jumps to about 0.5 if the cell is able to slightly
      loosen the tight packing, for example, by decreasing the diameter of the
      microvilli by only 2%. On the basis of our calculations, alteration of
      microvillus geometry represents a mechanism by which epithelial cells can
      efficiently regulate intercellular signaling.

PMID- 19601597
TI  - Thermal decomposition of hydrazines from reactive dynamics using the ReaxFF
      reactive force field.
AB  - We report reactive dynamics (RD) studies on: the decomposition of bulk hydrazine
      (N(2)H(4)); the decomposition of bulk monomethyl-hydrazine (CH(3)N(2)H(3)),
      hereafter referred to simply as methyl-hydrazine; the decomposition of hydrazine
      in the presence of hydrogen peroxide (H(2)O(2)); and decomposition hydrazine on
      catalytic surfaces Pt[100] and Pt[111] under various conditions. These studies
      use the ReaxFF reactive force field to describe the multitude of chemical
      reactions in these systems for a variety of reaction conditions in order to show
      that this approach leads to realistic decomposition mechanisms and rates. In
      particular, we determined how the decomposition of hydrazine is affected by
      temperature, pressure, and heating rate. We analyzed chemical reaction mechanism
      of the decomposition of hydrazine at the studied conditions and found that at
      lower temperatures the initial product from hydrazine decomposition is NH(3),
      whereas at higher temperatures H(2) and N(2) are the dominant early products.
      Prominent intermediates observed during these decompositions include N(2)H(3),
      N(2)H(2,) and NH(2), in agreement with quantum mechanical studies (7.3 ps at 3000
      K). As the heating rate is decreased, the onset for hydrazine decomposition
      shifts to lower temperatures. Using a constant heating rate, we found that higher
      pressure (increased density) favors formation of NH(3) over N(2) and H(2). In
      studies of the catalytic decomposition of hydrazine on surfaces Pt[100] and
      Pt[111], we found that the presence of a Pt-catalyst reduces the initial
      decomposition temperature of hydrazine by about 50%. We found that the Pt[100]
      surface is 20 times more active for hydrazine decomposition than the Pt[111]
      surface, in qualitative agreement with experiments. These studies indicate how
      ReaxFF RD can be useful in understanding the chemical processes involved in bulk
      and catalytic decomposition and in oxidation of reactive species under various
      reaction conditions.

PMID- 19601598
TI  - Structural organization and transport properties of novel pyrrolidinium-based
      ionic liquids with perfluoroalkyl sulfonylimide anions.
AB  - Room-temperature ionic liquids (RTILs) based on the N-butyl-N-methyl
      pyrrolidinium cation (PYR(14)(+)) combined with three different fluorinated
      anions have been prepared and characterized by NMR, conductivity, and rheological
      measurements. The anions are
      (trifluoromethanesulfonyl)(nonafluorobutanesulfonyl)imide (IM(14)(-)),
      bis(pentafluoroethanesulfonyl)imide (BETI(-)), and
      bis(trifluoromethanesulfonyl)imide (TFSI(-)). Intermolecular anion-cation nuclear
      Overhauser enhancements (NOEs) have been experimentally observed in all titled
      compounds. These findings indicate the formation of long-lived aggregates in the
      bulk liquids. The NOE patterns show marked selectivity and can be rationalized
      assuming that the perfluorinated moieties of the anions tend to adopt a
      preferential orientation with respect to the cations, with possible formation of
      mesoscopic fluorous domains. Self-diffusion coefficients D for the anion and the
      cation have been measured by DOSY NMR. Diffusion data show similar but not
      identical values for cation and anion, consistent with local ordering at the
      molecular level. The observed trend in diffusion coefficients, D(cation) >
      D(anion) for all compounds, is compatible with a higher degree of intermolecular
      organization of the anions. This nanoscale organization is connected to rather
      strong deviations of the experimental conductivities from those estimated from
      the ion diffusion coefficients through the Nernst-Einstein relationship. The
      measured viscosities and ion diffusion coefficients in PYR(14)IM(14) and in
      PYR(14)TFSI have similar temperature dependencies, leading to very close values
      of the activation energies for these processes. Ab initio density functional
      calculations on models of a PYR(14)TFSI ion pair lead to the identification of
      several local minima, whose structure and energy can be qualitatively related to
      the experimental NOE signals and activation energies.

PMID- 19601599
TI  - Asymmetric total synthesis of (-)-plicatic acid via a highly enantioselective and
      diastereoselective nucleophilic epoxidation of acyclic trisubstitued olefins.
AB  - The first total synthesis of (-)-plicatic acid has been achieved by a concise and
      enantioselective route. In this synthesis, a conceptually new strategy featuring
      an asymmetric epoxidation-intramolecular epoxy-ring-opening Friedel-Crafts
      reaction sequence was developed for the stereoselective construction of the 2,7'
      cyclolignane skeleton bearing contiguous quaternary-quaternary-tertiary
      stereocenters. The implementation of this strategy was enabled by the development
      of a modified protocol for the Seebach epoxidation with TADOOH, which affords an
      unprecedented, highly enantioselective and diastereoselective epoxidation with a
      range of alpha-carbonyl-beta-substituted acrylates 3.

PMID- 19601600
TI  - New palladium(II) complex of P,S-containing hybrid calixphyrin. Theoretical study
      of electronic structure and reactivity for oxidative addition.
AB  - The palladium complex of P,S-containing hybrid calixphyrin 1 was investigated
      with the DFT method. There are two kinds of valence tautomer in 1: one is a
      Pd(II) form in which the calixphyrin moiety possesses -2 charges and the Pd
      center takes +2 oxidation state, and the other is a Pd(0) form in which the
      calixphyrin is neutral and the Pd center takes zero oxidation state. Complex 1
      takes the Pd(II) form in the ground state. Though the Pd center takes +2
      oxidation state, DFT computations clearly show that the oxidative addition of
      phenyl bromide (PhBr) to 1 occurs with moderate activation enthalpy, as
      experimentally proposed. The first step of the oxidative addition is the
      coordination of PhBr with the Pd center to form intermediate 1INTa, in which the
      Pd center and the calixphyrin moiety are neutral; in other words, the valence
      tautomerization from the Pd(II) form to the Pd(0) form occurs in the palladium
      calixphyrin moiety. The activation enthalpy is 22.5 kcal/mol, and the enthalpy
      change of reaction is 20.3 kcal/mol. The next step is the C-Br sigma-bond
      cleavage of PhBr, which occurs with activation enthalpy of 2.0 kcal/mol relative
      to 1INTa. On the other hand, the oxidative additions of PhBr to palladium complex
      of P,S-containing hybrid porphyrin 2 and that of conventional porphyrin 3 need
      much larger activation enthalpies of 49.1 and 74.4 kcal/mol, respectively. The
      differences in the reactivity among 1, 2, and 3 were theoretically investigated;
      in 1, the valence tautomerization occurs with moderate activation enthalpy to
      afford the Pd(0) form which is reactive for the oxidative addition. In 2, the
      tautomerization from the Pd(II) form to the Pd(0) form needs very large
      activation enthalpy (43.3 kcal/mol). In 3, such valence tautomerization does not
      occur at all, indicating that the Pd(II) must change to the Pd(IV) in the
      oxidative addition of PhBr to 3, which is a very difficult process. These
      differences are interpreted in terms of the pi* orbital energies of P,S
      containing hybrid calixphyrin, hybrid porphyrin, and conventional porphyrin and
      the flexibility of their frameworks.

PMID- 19601601
TI  - Large metal ions in a relatively small fullerene cage: the structure of
      Gd3N@C2(22010)-C78 departs from the isolated pentagon rule.
AB  - An isomerically pure sample of Gd(3)N@C(78) has been extracted from the carbon
      soot formed in the electric-arc generation of fullerenes using hollow graphite
      rods packed with Gd(2)O(3) and graphite powder under an atmosphere of helium and
      dinitrogen. Purification has been achieved by chromatographic methods and the
      product has been characterized by mass spectrometry, UV/vis absorption
      spectroscopy, and cyclic voltammetry. Although a number of endohedral fullerenes
      have been found to utilize the D(3h)(5)-C(78) cage, comparison of the
      spectroscopic and electrochemical properties of the previously characterized
      Sc(3)N@D(3h)(5)-C(78) with those of Gd(3)N@C(78) reveals significant differences
      that indicate that these two endohedrals do not possess the same cage structure.
      A single crystal X-ray diffraction study indicates that the fullerene cage does
      not follow the isolated pentagon rule (IPR) but has two equivalent sites where
      two pentagons abut. The endohedral has been identified as Gd(3)N@C(2)(22010)
      C(78). Two of the gadolinium atoms of the planar Gd(3)N unit are located within
      the pentalene folds formed by the adjacent pentagons. The third gadolinium atom
      resides at the center of a hexagonal face of the fullerene.

PMID- 19601603
TI  - Multiconfiguration Dirac-Hartree-Fock adjusted energy-consistent pseudopotential
      for uranium: spin-orbit configuration interaction and Fock-space coupled-cluster
      study of U4+ and U5+.
AB  - In order to assess the accuracy of a recently adjusted relativistic energy
      consistent small-core pseudopotential for uranium, the U(5+) (5f(1)
      subconfiguration) spin-orbit splitting as well as the fine structure of the U(4+)
      (5f(2) subconfiguration) spectrum have been calculated. The pseudopotential has
      been adjusted to four-component all-electron data, i.e., at the
      multiconfiguration Dirac-Hartree-Fock level using the Dirac-Coulomb Hamiltonian
      with a Fermi nucleus charge distribution and perturbatively including the Breit
      interaction. Its performance in a dressed effective Hamiltonian spin-orbit
      configuration interaction framework is compared to that of an older scalar
      relativistic Wood-Boring adjusted pseudopotential, supplemented by a valence spin
      orbit term, as well as to all-electron calculations using the Douglas-Kroll-Hess
      Hamiltonian. Electron correlation is accounted for by the multireference
      configuration interaction method with and without the Davidson correction and
      with different frozen-orbital spaces. Our best calculations show satisfactory
      agreement with experimental data; i.e., the mean absolute (relative) deviations
      amount to 183 (2.4%) and 948 cm(-1) (5.1%) for the U(5+) and the U(4+) fine
      structure energy levels, respectively. Even better agreement, comparable to the
      one for rigorous highly correlated four-component all-electron data, is obtained
      in intermediate Hamiltonian Fock-space coupled-cluster calculations applying the
      new pseudopotential.

PMID- 19601605
TI  - An intersection inequality sharper than the tanimoto triangle inequality for
      efficiently searching large databases.
AB  - Bounds on distances or similarity measures can be useful to help search large
      databases efficiently. Here we consider the case of large databases of small
      molecules represented by molecular fingerprint vectors with the Tanimoto
      similarity measure. We derive a new intersection inequality which provides a
      bound on the Tanimoto similarity between two fingerprint vectors and show that
      this bound is considerably sharper than the bound associated with the triangle
      inequality of the Tanimoto distance. The inequality can be applied to other
      intersection-based similarity measures. We introduce a new integer representation
      which relies on partitioning the fingerprint components, for instance by taking
      components modulo some integer M and reporting the total number of 1-bits falling
      in each partition. We show how the intersection inequality can be generalized
      immediately to these integer representations and used to search large databases
      of binary fingerprint vectors efficiently.

PMID- 19601604
TI  - Gaussia luciferase variant for high-throughput functional screening applications.
AB  - Gaussia luciferase (Gluc) is a sensitive reporter for studying different
      biological processes such as gene expression, promoter activity, protein-protein
      interactions, signal transduction, as well as tumor cell growth and response to
      therapy. Since Gluc is naturally secreted, the kinetics of these processes can be
      monitored in real-time by measuring an aliquot of conditioned medium in culture
      or a few microliters of blood in vivo at different time points. Gluc catalyzes
      light emission with a short half-life which is unfavorable for certain
      applications. We isolated a Gluc mutant that catalyzes enhanced light stability
      in the presence of a detergent, in combination with high sensitivity, making it
      an attractive luciferase for high-throughput functional screening applications.

PMID- 19601606
TI  - Synthesis of binuclear complexes bound in an enlarged tetraphosphamacrocycle: two
      diphosphine metal units linked in front-to-front style.
AB  - A large-hole tetraphosphamacrocycle 2, with four phosphorus centers separated at
      the corners of a 3.7 A wide and 9.7 A long rectangle, was synthesized by a
      stepwise cyclization reaction between PCl-bridged [1.1]ferrocenophane and
      bisphenol A in a 2:2 ratio. The macrocycle 2 could incorporate two Ag(+) or Pt(0)
      fragments in the hole to provide binuclear complexes, which were identified as mu
      2-[Ag(NCMe)(2)](2)(BF(4))(2) (3) and mu-2-[Pt(PhCCPh)](2) (5), respectively,
      using X-ray and spectroscopic analysis. The X-ray structure of 3 demonstrates
      that the macrocycle 2 serves as a framework in which two diphosphine silver units
      are aligned in a front-to-front style, while that of 5 indicates that 2 can also
      bind two bulky Pt(PhCCPh) fragments by the flexible change of its conformation.

PMID- 19601607
TI  - Bioactive diterpene derivatives from the marine sponge Spongionella sp.
AB  - Three new compounds of the rare classes trisnorditerpenes, bisnorditerpenes, and
      norditerpenes, gracilins J-L (1, 2, 6), and a new diterpene, 3'-norspongiolactone
      (8), were isolated from the extract of the marine sponge Spongionella sp. using
      NMR- and bioassay-guided fractionation, in addition to three known gracilins (3
      5) as well as the known diterpenoid tetrahydroaplysulphurin-1 (7). The structures
      were elucidated using NMR spectroscopic techniques and mass spectrometric
      analysis. The structure of gracilin H (3) was confirmed by single-crystal X-ray
      analysis. All compounds were tested for their cytotoxicity and for their
      potential to inhibit EGF-R tyrosine kinase.

PMID- 19601608
TI  - An interrupted Fischer indolization approach toward fused indoline-containing
      natural products.
AB  - An efficient method to access the fused indoline ring system present in a
      multitude of bioactive molecules has been developed. The strategy involves the
      condensation of hydrazines with latent aldehydes to ultimately deliver indoline
      containing products by way of an interrupted Fischer indolization sequence. Our
      studies show that the approach will likely be amenable to the synthesis of
      complex targets, such as the communesin natural products.

PMID- 19601610
TI  - Photobleaching of the "Raman spectroscopic signature of life" and mitochondrial
      activity in rho- budding yeast cells.
AB  - Raman spectra of mitochondria in single living budding yeast (zygote of
      Saccharomyces cerevisiae and Saccharomyces bayanus) cells have been measured and
      compared for two types of tetraploid strains, the wild-type strain and the rho-
      strain. The "Raman spectroscopic signature of life", a strong Raman band at 1602
      cm(-1) that sharply reflects the mitochondrial activity, has been found in both
      of the two strains with similar intensities. This signature showed photobleaching
      under irradiation of the 632.8 nm line of a He-Ne laser, only for the rho-
      strain. The photobleaching recovered by keeping the cell in the dark for two
      hours without laser irradiation. These findings indicate that the molecular
      species that gives rise to the 1602 cm(-1) band is an intermediate formed and
      accumulated during the metabolic cycle and that it absorbs at 632.8 nm to undergo
      photodecomposition. We also found a number of weak Raman bands in the 400-1200
      cm(-1) region that show the same temporal behaviors as that of the 1602 cm(-1)
      band by an SVD analysis of time-resolved Raman spectra. Several new pieces of
      information on the origin of the "Raman spectroscopic signature of life" have
      thus been obtained.

PMID- 19601609
TI  - Taking advantage of electrostatic interactions to grow Langmuir-Blodgett films
      containing multilayers of the phospholipid dipalmitoylphosphatidylglycerol.
AB  - The use of phospholipids as mimetic systems for studies involving the cell
      membrane is a well-known approach. In this context, the Langmuir and Langmuir
      Blodgett (LB) methods are among the main techniques used to produce ordered
      layers of phospholipids structured as mono- or bilayers on water subphase and
      solid substrates. However, the difficulties of producing multilayer LB films of
      phospholipids restrict the application of this technique depending on the
      sensitivity of the experimental analysis to be conducted. Here, an alternative
      approach is used to produce LB films containing multilayers of the negative
      phospholipid dipalmitoylphosphatidylglycerol (DPPG). Inspired by the
      electrostatic layer-by-layer (LbL) technique, DPPG multilayer LB films were
      produced by transferring the DPPG Langmuir monolayers from the water subphase
      containing low concentrations of the cationic polyelectrolyte poly(allylamine
      hydrochloride) (PAH) onto solid substrates. Fourier transform infrared (FTIR)
      absorption spectroscopy revealed that the interactions between the NH(3)(+) (PAH)
      and PO(4)(-) (DPPG) groups might be the main driving forces that allow growth of
      these LB films. Besides, ultraviolet-visible (UV-vis) absorption spectroscopy
      showed that the multilayer LB films can be grown in a controlled way in terms of
      thickness at nanometer scale. Cyclic voltammetry showed that DPPG and PAH are
      more packed in the LB than LbL films. The latter finding is related to the
      distinct molecular architecture of the films since DPPG is structured as
      monolayers in the LB films and multilamellar vesicles in the LbL films. Despite
      the interaction with PAH, cyclic voltammetry also showed that DPPG retains its
      biological activity in LB films, which is a key factor since this makes DPPG a
      suitable material in sensing applications. Therefore, multilayer LB films were
      deposited onto Pt interdigitated electrodes forming sensing units, which were
      applied in the detection of a phenothiazine compound [methylene blue (MB)] using
      impedance spectroscopy. The performance of DPPG in single-layer and multilayer LB
      films was compared to the performance of sensing unities composed of DPPG in
      single-layer and multilayer LbL films, showing the importance of both the
      thickness and the molecular architecture of the thin films. As found in a
      previous work for LbL films, the high sensitivity reached by these sensing units
      is intimately related to changes in the morphology of the film as evidenced by
      the micro-Raman technique. Finally, the interaction between MB and the (DPPG+PAH)
      LB films was complemented by pi-A isotherms and surface-enhanced resonance Raman
      scattering (SERRS).

PMID- 19601611
TI  - Molecular dynamics simulations on the stability and assembly mechanisms of
      quadruple and double helical aromatic amide foldamers.
AB  - The polymer of 7-amino-8-fluoro-2-quinoline carboxylic acid (abbreviated as
      QF(n), n denotes polymerization degree, where n = 4 or 8) can form artificial
      helices that do not exist in nature. The crystal structures of the quadruplex of
      QF(4) and the duplex of QF(8) (abbreviated as QP_4 and DP_8, respectively) have
      been unveiled by some researchers recently. In this paper, QP_4 and DP_8 were
      built based on their crystal structures. Though the quadruplex of QF(8) and the
      duplex of QF(4) (abbreviated as QP_8 and DP_4, respectively) were not observed in
      experiments, they were built using molecular modeling tools. The molecular
      dynamics (MD) method was used to study the stabilities and assembly mechanisms of
      these helices at different temperatures. In MD simulations, the disassembled QP_4
      was observed above 480 K. The results indicate that these oligoamide helices
      showed slippage of strands to some extent and that double-helical oligoamides act
      as a basic block in the slippage during the formation of the quadruple-helical
      structure. DP_4 and QP_4 showed dynamical features with helix-handedness
      inversion and following slippage of strands at higher temperatures. In addition,
      the pi-pi conjugations between the different chains are supposed to be
      responsible for the stability of the helices.

PMID- 19601612
TI  - Solvatochromic fluorescence of piperazine-modified bipyridazines for an organic
      solvent-sensitive film.
AB  - Bipyridazines were modified with heterocyclic amines such as piperazine to give
      symmetric quadrupolar (SPBP) and asymmetric dipolar (APBP) bipyridazine. The
      fluorescence of SPBP and APBP was highly sensitive to solvent polarity, giving a
      synthetic rainbow of emission in different organic solvents. The solvent-induced
      changes in the Stokes shift of the bipyridazines resulted in positive
      solvatochromism. The symmetric bipyridazine showed higher solvatochromic
      sensitivity than that of the asymmetric bipyridazine and diazines. The positive
      solvatochromic fluorescence properties were reproduced in a binary system of
      toluene/dimethyl sulfoxide (DMSO) mixture, which showed a synthetic rainbow of
      emission by varying the DMSO content in toluene. An organic sensitive poly(methyl
      methacrylate) film containing SPBP exhibited a visible sensitivity for the
      detection of solvents by their polarity upon exposure to organic solvent
      molecules.

PMID- 19601613
TI  - Ruthenium(II) terpyridyl complexes exhibiting DNA photocleavage: the role of the
      substituent on monodentate ligand.
AB  - Five ruthenium(II) complexes, [Ru(II)(tpy)(dppz)(py-R)](2+) (tpy = 2,2':6',2''
      terpyridine; dppz = dipyrido[3,2-a:2',3'-c]phenazine; py-R = 4-substituted
      pyridine; R = N(CH(3))(2), NH(2), OCH(3), H, NO(2)), were synthesized; and the
      substituent effects on the photophysical property, electrochemical property, DNA
      binding, and DNA photocleavage of the complexes were examined carefully.
      Increasing the electron-donating ability of the substituent R from NO(2) to
      N(CH(3))(2) leads to a cathodic shift of Ru-based oxidation potential, a red
      shift of the (1)MLCT absorption at room temperature and the (3)MLCT emission at
      77 K, and enhancement of the DNA photocleavage ability. DNA photocleavage control
      experiments and the EPR spin-trapping technique confirm that the photocleavage
      abilities of the complexes originate from (1)O(2) production. Time-resolved
      absorption spectra suggest that the (3)MLCT lifetime plays an important role in
      the photosensitized (1)O(2) generation of these complexes, which in turn depends
      strongly on the electron-donating ability of the substituent R. By changing the
      substituent of pyridine from the electron-withdrawing to the electron-donating
      group, the photocleavage abilities of the complexes varied from inactive to
      active, providing a new strategy for the development of DNA photocleavers of tpy
      based Ru(II) complexes.

PMID- 19601614
TI  - Matrix infrared spectroscopic and computational investigation of late lanthanide
      metal hydride species MH(x)(H(2))(y) (M = Tb-Lu, x = 1-4, y = 0-3).
AB  - Laser-ablated late lanthanide metal atoms were condensed with pure hydrogen at 4
      K, and new infrared absorptions are assigned to binary metal hydrides on the
      basis of deuterium substitution and density functional theory frequency
      calculations. The dominant absorptions in the 1330-1400 cm(-1) region are
      identified as LnH(3) complexes with very weak ligand bands near 3900 cm(-1). With
      ytterbium, YbH and YbH(2) were the major initial products, but YbH(3) increased
      at their expense upon sample irradiation. Evidence is also presented for the LuH
      and ErH molecules and the tetrahydride anions in solid hydrogen.

PMID- 19601615
TI  - Oxidation of copper(I) hexaaza macrocyclic dinuclear complexes.
AB  - DFT calculations give insight into the formation of peroxo intermediates 1-8 from
      a series of Cu(I) complexes bearing N-hexadentated macrocyclic dinucleating
      ligands, suffering an oxidation by their interaction with molecular oxygen. The
      discussion is thus based on the side-on peroxo cores, omitting the case of
      complex 8 for which the most favored structure is the trans-peroxo due to para
      substitution and the steric encumbrance produced by the methylation of the aminic
      N atoms. The frontier molecular orbital theory explains deeply the O2 binding to
      the Cu(I) complexes, giving key relationships between the energy of particular
      orbitals of the copper complex before the O2 binding and the corresponding ones
      for the free O2. On the other hand, tools such as the energy decomposition
      analysis and Mayer bond orders reveal the slight differences due to the different
      types of ligands.

PMID- 19601616
TI  - A convenient synthesis of tetrabenzo[de,hi,mn,qr]naphthacene from readily
      available 1,2-di(phenanthren-4-yl)ethyne.
AB  - We report here a convenient synthesis of tetrabenzo[de,hi,mn,qr]naphthacenes from
      1,2-di(phenanthren-4-yl)ethynes through initial Bronsted acid-catalyzed
      hydroarylation, followed by FeCl(3)-oxidative coupling reactions. This new method
      is applicable to tetrabenzo[de,hi,mn,qr]naphthacenes bearing various alkyl
      substituents.

PMID- 19601617
TI  - Mass cytometry: technique for real time single cell multitarget immunoassay based
      on inductively coupled plasma time-of-flight mass spectrometry.
AB  - A novel instrument for real time analysis of individual biological cells or other
      microparticles is described. The instrument is based on inductively coupled
      plasma time-of-flight mass spectrometry and comprises a three-aperture plasma
      vacuum interface, a dc quadrupole turning optics for decoupling ions from neutral
      components, an rf quadrupole ion guide discriminating against low-mass dominant
      plasma ions, a point-to-parallel focusing dc quadrupole doublet, an orthogonal
      acceleration reflectron analyzer, a discrete dynode fast ion detector, and an 8
      bit 1 GHz digitizer. A high spectrum generation frequency of 76.8 kHz provides
      capability for collecting multiple spectra from each particle-induced transient
      ion cloud, typically of 200-300 micros duration. It is shown that the transients
      can be resolved and characterized individually at a peak frequency of 1100
      particles per second. Design considerations and optimization data are presented.
      The figures of merit of the instrument are measured under standard inductively
      coupled plasma (ICP) operating conditions (<3% cerium oxide ratio). At mass
      resolution (full width at half-maximum) M/DeltaM > 900 for m/z = 159, the
      sensitivity with a standard sample introduction system of >1.4 x 10(8) ion counts
      per second per mg L(-1) of Tb and an abundance sensitivity of (6 x 10(-4))-(1.4 x
      10(-3)) (trailing and leading masses, respectively) are shown. The mass range
      (m/z = 125-215) and abundance sensitivity are sufficient for elemental
      immunoassay with up to 60 distinct available elemental tags. When <15 elemental
      tags are used, a higher sensitivity mode at lower resolution (M/DeltaM > 500) can
      be used, which provides >2.4 x 10(8) cps per mg L(-1) of Tb, at (1.5 x 10(-3))
      (5.0 x 10(-3)) abundance sensitivity. The real-time simultaneous detection of
      multiple isotopes from individual 1.8 microm polystyrene beads labeled with
      lanthanides is shown. A real time single cell 20 antigen expression assay of
      model cell lines and leukemia patient samples immuno-labeled with lanthanide
      tagged antibodies is presented.

PMID- 19601618
TI  - Potential-dependent characterization of bombesin adsorbed states on roughened Ag,
      Au, and Cu electrode surfaces at physiological pH.
AB  - This paper reports the direct surface-enhanced Raman spectroscopic (SERS) and
      generalized two-dimensional correlation analysis observations of the different
      orientations of the neurotransmitter bombesin (BN) chemisorbed on
      electrochemically roughened Ag, Au, and Cu electrode surfaces at different
      applied electrode potentials and at physiological pH. The presence of the indole
      ring of Trp(8) and the amide bond between Gln(7) and Trp(8) of BN on these
      surfaces generates a specific SERS profile of BN adsorbed on the roughened Ag and
      Au electrodes that is affected by the electrode potential. Furthermore, for BN on
      Au, slight changes are observed in the band enhancement in comparison to what is
      observed for this neurotransmitter immobilized on Ag. In addition, there are
      larger changes in the spectra triggered by the substitution of Ag with Au
      electrodes and Ag with Cu electrodes than by substitution of Au with Cu
      electrodes.

PMID- 19601619
TI  - Directional surface plasmon coupled luminescence for analytical sensing
      applications: which metal, what wavelength, what observation angle?
AB  - The ability of luminescent species in the near-field to both induce and couple to
      surface plasmons has been known for many years, with highly directional emission
      from films (Surface Plasmon Coupled Luminescence, SPCL) facilitating the
      development of sensitive near-field assay sensing platforms, to name but just one
      application. Because of the near-field nature of the effect, only luminescent
      species (fluorescence, chemiluminescence and phosphorescence) within a few
      hundred nanometers from the surface play a role in coupling, which in terms of
      biosensing, provides for limited penetration into optically dense media, such as
      in whole blood. Another attractive feature is the highly polarized and angular
      dependent emission which allows both fixed angle and wavelength dependent
      emission angles to be realized at high polarization ratios. In this paper, a
      generic procedure based on theoretical Fresnel calculations, which outlines the
      step-by-step selection of an appropriate metal for SPCL applications is
      presented. It is also shown that 11 different metals have differing properties in
      different spectral regions and offer either fixed angle or wavelength-dependent
      angular shifts in emission. In addition, it is shown that both chemiluminescence
      and phosphorescence can also be observed in a highly directional manner similar
      to coupled fluorescence.

PMID- 19601620
TI  - Protein quantification in complex mixtures by solid phase single-molecule
      counting.
AB  - Here we present a procedure for quantifying single protein molecules affixed to a
      surface by counting bound antibodies. We systematically investigate many of the
      parameters that have prevented the robust single-molecule detection of surface
      immobilized proteins. We find that a chemically adsorbed bovine serum albumin
      surface facilitates the efficient detection of single target molecules with
      fluorescent antibodies, and we show that these antibodies bind for lengths of
      time sufficient for imaging billions of individual protein molecules. This
      surface displays a low level of nonspecific protein adsorption so that bound
      antibodies can be directly counted without employing two-color coincidence
      detection. We accurately quantify protein abundance by counting bound antibody
      molecules and perform this robustly in real-world serum samples. The number of
      antibody molecules we quantify relates linearly to the number of immobilized
      protein molecules (R(2) = 0.98), and our precision (1-5% CV) facilitates the
      reliable detection of small changes in abundance (7%). Thus, our procedure allows
      for single, surface-immobilized protein molecules to be detected with high
      sensitivity and accurately quantified by counting bound antibody molecules.
      Promisingly, we can probe flow cells multiple times with antibodies, suggesting
      that in the future it should be possible to perform multiplexed single-molecule
      immunoassays.

PMID- 19601621
TI  - Convenient method for modifying poly(dimethylsiloxane) with poly(ethylene glycol)
      in microfluidics.
AB  - This report describes a convenient and reproducible method for the covalent
      modification of poly(dimethylsiloxane) (PDMS) with poly(ethylene glycol) (PEG)
      chains to suppress nonspecific protein adsorption. PEG additives terminated with
      a vinyl group are added into the PDMS prepolymer; when the PDMS is thermally
      cured, the vinyl group reacts with the silane groups on the PDMS, which
      covalently link the PEG group to the PDMS network. The PEG-modified PDMS surfaces
      are characterized with FT-IR, X-ray photoelectron spectroscopy (XPS), and contact
      angle measurement. We also examined the modified PDMS for on-chip capillary
      electrophoresis and its capability of resisting nonspecific protein adsorption
      using bovine serum albumin (BSA) as a model. Based on our study, a molecular
      mechanism is given to successfully explain the surface properties of the modified
      PDMS surfaces.

PMID- 19601622
TI  - Femtosecond spectroscopy from the perspective of a global multidimensional
      response function.
AB  - At the microscopic level, multidimensional response functions, such as the
      nonlinear optical susceptibility or the time-ordered response function, are
      commonly used tools in nonlinear optical spectroscopy for determining the
      nonlinear polarization resulting from an arbitrary excitation. In this Account,
      we point out that the approach successfully developed for the nonlinear
      polarization can also be used in the case of a directly observable macroscopic
      quantity. This observable can be, for example, the electric field radiated in a
      nonlinear mixing experiment, the rate of fluorescence resulting from one- or two
      photon absorption, or the rate of a photochemical reaction. For each of these
      physical processes, perturbation theory can be used to expand the measured
      quantity in a power series of the exciting field, and an appropriate global
      response function can be introduced for each order of perturbation. At order n,
      the multidimensional response function will depend on n variables (either time or
      frequency) and have the same general properties as the nonlinear susceptibility
      resulting, for example, from time invariance or causality. The global response
      function is introduced in this Account in close analogy with the nonlinear
      susceptibility or the time-ordered microscopic response. We discuss various
      applications of the global response function formalism. For example, it can be
      shown that in the weak field limit, a stationary signal induced in a time
      invariant system is independent of the spectral phase of the exciting field.
      Although this result had been demonstrated previously, the global response
      function enables its derivation in a more general way because no specific
      microscopic model is needed. Multidimensional spectroscopy is obviously ideally
      suited to measure the global multidimensional response function. It is shown that
      the second (or third)-order response can be exactly measured with 2D (or 3D)
      spectroscopy by taking into account the exact shape of the exciting pulses. In
      the case of a 2D measurement of the third-order response, a particular projection
      of the complete 3D response function is actually measured. This projection can be
      related to a mixed time and frequency representation of the response function
      when the pulses are assumed to be infinitely short. We thus show that the global
      response function is a useful tool for deriving general results and that it
      should help in designing future experimental schemes for femtosecond
      spectroscopy.

PMID- 19601623
TI  - Solid-phase-microextraction measurement of 62 polychlorinated biphenyl congeners
      in milliliter sediment pore water samples and determination of K(DOC) values.
AB  - Determining dissolved concentrations of polychlorinated biphenyls (PCBs) in
      sediment pore (interstitial) water with conventional solvent extraction methods
      is problematic because obtaining large (liter) quantities of pore water,
      separating it from the sediment, and removing the influence of colloids can be
      very difficult. However, solid-phase-microextraction (SPME) can achieve similar
      detection limits using milliliter water samples as achieved with organic solvent
      extraction requiring a liter of pore water. Five different SPME sorbents were
      evaluated for their ability to yield the best detection limits for di- to
      octachlorobiphenyl congeners, both with GC/ECD and with GC/MS (both positive ion
      EI and negative ion CI). SPME using the 7 microm PDMS fiber with GC/MS (positive
      ion EI) yielded the best combination of signal-to-noise and selectivity using a
      30 min extraction, although ECD was also suitable. Pore water was obtained by
      centrifuging wet sediment followed by flocculation to remove colloids.
      Quantitative calibration was simplified by adding dichloro- to hexachlorobiphenyl
      internal standards chosen to be compatible with either ECD or MS detection.
      Calibration curves and relative response factors (including the SPME and GC
      steps) were determined for all 62 PCB congeners that are present in above-trace
      quantities in commercial Aroclors. Calibrations were linear (r(2) typically
      >0.995) from low pg/mL to ng/mL concentrations, with near zero intercepts.
      Detection limits for all individual PCB congeners ranged from <1 to 3 pg/mL using
      1.5 mL water samples. Dissolved organic matter (DOM) had no measurable effect on
      dichloro- and trichlorobiphenyls, but did contain about 10 to 25% of the
      tetrachlorobiphenyls and up to 60% of the hexachlorobiphenyl congeners. Log
      DOC/water partitioning coefficients (log K(DOC)) ranged from 3.6 to 4.6 for
      2,3,5,6-tetrachlorobiphenyl and from 4.2 to 5.5 for 3,3',4,4',5,5'
      hexachlorobiphenyl.

PMID- 19601624
TI  - Flash reduction and patterning of graphite oxide and its polymer composite.
AB  - Graphite oxide (GO) is a promising precursor for the bulk production of graphene
      based materials due to its relatively low cost of synthesis. The superior solvent
      processability of GO makes it particularly attractive for making composites by
      premixing with other materials. Typically, the reduction of GO has relied on
      either chemical agents or high temperature treatment. Here we report a room
      temperature, chemical-free flash reduction process where a photographic camera
      flash instantaneously triggers the deoxygenation reaction of GO by photothermal
      heating. Flash irradiation also rapidly creates a fused polymer composite from a
      random mixture of GO and polymer particles. Using a photomask, conducting
      patterns such as interdigitated electrode arrays can be readily made on flexible
      substrates.

PMID- 19601625
TI  - Isolated seven-coordinate Ru(IV) dimer complex with [HOHOH](-) bridging ligand as
      an intermediate for catalytic water oxidation.
AB  - With the inspiration from an oxygen evolving complex (OEC) in Photosystem II
      (PSII), a mononuclear Ru(II) complex with a tetradentate ligand containing two
      carboxylate groups has been synthesized and structurally characterized. This
      Ru(II) complex showed efficient catalytic properties toward water oxidation by
      the chemical oxidant cerium(IV) ammonium nitrate. During the process of catalytic
      water oxidation, Ru(III) and Ru(IV) species have been successfully isolated as
      intermediates. To our surprise, X-ray crystallography together with HR-MS
      revealed that the Ru(IV) species is a seven-coordinate Ru(IV) dimer complex
      containing a [HOHOH](-) bridging ligand. This bridging ligand has a short O...O
      distance and is hydrogen bonded to two water molecules. The discovery of this
      very uncommon seven-coordinate Ru(IV) dimer together with a hydrogen bonding
      network may contribute to a deeper understanding of the mechanism for catalytic
      water oxidation. It will also provide new possibilities for the design of more
      efficient catalysts for water oxidation, which is the key step for solar energy
      conversion into hydrogen by light-driven water splitting, the ultimate challenge
      in artificial photosynthesis.

PMID- 19601626
TI  - Electrocatalytic responses at mediator modified electrodes with several cyclic
      step and cyclic sweep potential techniques. Application to the oxidation of
      ascorbate at a ferrocene-monolayer modified gold electrode.
AB  - Analytical expressions for the current-potential and charge-potential curves of
      an electrocatalytic process taking place at redox mediator modified electrodes
      corresponding to the application of cyclic staircase or cyclic sweep potentials
      are presented. Simple equations for cyclic voltammetry and cyclic voltcoulometry
      curves have been also deduced for the usual experimental case corresponding to
      high catalytic rate constants, showing that whereas the current reach an
      stationary behavior, the charge always depend on time. The value of the rate
      constant of the chemical step can be easily determined from the plateau of the
      voltammogram or from the linear anodic region of the charge potential curves. The
      theoretical predictions have been tested with the electrocatalytic oxidation of
      ascorbate mediated by a mixed 6-(ferrocenyl)hexanethiol-butanethiol monolayer at
      a disk gold electrode, with an excellent agreement between theory and
      experiments. A catalytic rate constant 3440 M(-1) s(-1) has been obtained, which
      is higher than those previously reported for this system with longer alkanethiol
      chains.

PMID- 19601627
TI  - Aroma release from wines under dynamic conditions.
AB  - Aroma release from wines and model ethanolic solutions during dynamic headspace
      dilution was measured in real time using atmospheric pressure chemical ionization
      mass spectrometry. Model ethanolic solutions maintained the headspace
      concentration of volatile compounds close to equilibrium values during gas phase
      dilution over 10 min. Wine samples (with the same ethanol content) did not
      maintain the headspace concentration of volatiles to the same extent. Wine
      components and acidity ((+)-catechin, glycerol; pH 3.6) in model ethanolic
      solutions (120 mL/L) had no effect on the volatile headspace concentration during
      dynamic headspace dilution. However, in the presence of certain proteins (beta
      lactoglobulin, beta-casein, bovine serum albumin), the model ethanolic solutions
      failed to maintain their volatile headspace concentration upon headspace
      dilution, but other proteins (thaumatin, mucin, lysozyme) had no effect. Thermal
      imaging of the model ethanolic samples (with and without beta-casein) under
      dynamic headspace dilution conditions showed differences in surface temperatures.
      This observation suggested perturbation of the ethanol monolayer at the air
      liquid interface and disruption of the Marangoni effect, which causes bulk
      convection within ethanolic solutions. Convection carries volatile compounds and
      warm liquid from the bulk phase to the air-liquid interface, thus replenishing
      the interfacial concentration and maintaining the gas phase concentration and
      interfacial surface temperature during headspace dilution. It is postulated that
      certain proteins may exert a similar effect in wine.

PMID- 19601628
TI  - (-)-Epigallocatechin-3-gallate induces apoptosis of human hepatoma cells by
      mitochondrial pathways related to reactive oxygen species.
AB  - The aim of this study was to investigate the effects of (-)-epigallocatechin-3
      gallate (EGCG) on the induction of apoptosis in hepatocarcinoma cell lines in
      vitro and further examine the molecular mechanisms of EGCG-induced apoptosis. In
      the present study, it was observed that EGCG rapidly induced apoptosis in
      hepatocarcinoma SMMC7721 cells. EGCG-induced apoptosis was in association with
      the attenuation of mitochondrial transmembrane potentials (Deltapsi(m)), the
      alteration of Bcl-2 family proteins, the release of cytochrome c from
      mitochondria into the cytosol, and the activation of caspase-3 and caspase-9.
      Elevation of intracellular reactive oxygen species (ROS) production was also
      shown during EGCG-induced apoptosis of hepatocarcinoma SMMC7721 cells. The
      antioxidant N-acetyl-l-cysteine (NAC) significantly reduced ROS production and
      EGCG-induced apoptosis, suggesting that ROS plays a key role in EGCG-induced
      apoptosis in hepatocarcinoma SMMC7721 cells. In summary, EGCG-induced apoptosis
      through mitochondrial pathways, and ROS affected EGCG-induced apoptosis in
      hepatocarcinoma SMMC7721 cells.

PMID- 19601629
TI  - Chemical characteristics of Salvia miltiorrhiza (Danshen) collected from
      different locations in China.
AB  - The chemical characteristics of Salvia miltiorrhiza , also called "danshen" in
      China, were investigated on the basis of the simultaneous quantitative
      determination of 13 hydrophilic and lipophilic compounds, namely, protocatechuic
      acid, protocatechuic aldehyde, caffeic acid, ferulic acid, isoferulic acid,
      rosmarinic acid, salvianolic acid B, salvianolic acid A, dihydrotanshinone I,
      przewalskin, cryptotanshinone, tanshinone I, and tanshinone IIA, in 74 samples
      collected from different locations using ultraperformance liquid chromatography
      (UPLC). Hierarchical clustering analysis based on 13 investigated compounds and
      the similarity of the entire chromatographic pattern showed that S. miltiorrhiza
      was significantly different from Salvia przewalskii , an adulterant of danshen.
      The chemical characteristics of S. miltiorrhiza collected from different
      locations in China were revealed, and salvianolic acid B, rosmarinic acid,
      cryptotanshinone, and tanshinones I and IIA were optimized as markers for the
      evaluation, which is helpful in the quality control of S. miltiorrhiza.

PMID- 19601630
TI  - Structural and emulsifying properties of soy protein isolate subjected to acid
      and alkaline pH-shifting processes.
AB  - Structural unfolding of soy protein isolate (SPI) as induced by holding (0, 0.5,
      1, 2, and 4 h) in acidic (pH 1.5-3.5) and alkaline (pH 10.0-12.0) pH solutions,
      followed by refolding (1 h) at pH 7.0, was analyzed. Changes in emulsifying
      properties of treated SPI were then examined. The pH-shifting treatments resulted
      in a substantial increase in protein surface hydrophobicity, intrinsic tryptophan
      fluorescence intensity, and disulfide-mediated aggregation, along with the
      exposure of tyrosine. After the pH-shifting processes, soy protein adopted a
      molten globule-like conformation that largely maintained the original secondary
      structure and overall compactness but lost some tertiary structure. These
      structural modifications, consequently, led to markedly improved emulsifying
      activity of SPI as well as the emulsion stability.

PMID- 19601631
TI  - Bioaerosol analysis with Raman chemical imaging microspectroscopy.
AB  - Raman chemical imaging microspectroscopy is evaluated as a technology for
      waterborne pathogen and bioaerosol detection. Raman imaging produces a three
      dimensional data cube consisting of a Raman spectrum at every pixel in a
      microscope field of view. Binary and ternary mixtures including combinations of
      polystyrene beads, gram-positive Bacillus anthracis, B. thuringiensis, and B.
      atrophaeus spores, and B. cereus vegetative cells were investigated by Raman
      imaging for differentiation and characterization purposes. Bacillus spore aerosol
      sizes were varied to provide visual proof for corroboration of spectral
      assignments. Conventional applications of Raman imaging consist of
      differentiating relatively broad areas of a sample in a microscope field of view.
      The spectral angle mapping data analysis algorithm was used to compare a library
      spectrum with experimental spectra from pixels in the microscope field of view.
      This direct one-to-one matching is straightforward, does not require a training
      set, is independent of absolute spectral intensity, and only requires univariate
      statistics. Raman imaging is expanded in its capabilities to differentiate and
      distinguish between discrete 1-6 microm size bacterial species in single
      particles, clusters of mixed species, and bioaerosols with interference
      background particles.

PMID- 19601632
TI  - Analysis of RP-HPLC loading conditions for maximizing peptide identifications in
      shotgun proteomics.
AB  - Substantial energy and resources have been invested in improving mass
      spectrometry (MS) instrumentation, upstream sample preparation protocols, and
      database search strategies to maximize peptide and protein identifications. The
      role of HPLC sample loading methods in maximizing MS identifications has been
      largely overlooked, and there exists an immense heterogeneity in the methods
      employed in the proteomics literature. We sought to optimize loading methods by
      testing multiple loading conditions (buffer composition, resin, initial gradient)
      using tryptic digests of an 18 protein mixture and whole yeast lysate. The
      loading buffer acetonitrile (ACN) concentration greatly affected peptide
      identifications: up to a 26% increase in peptide identifications was observed by
      decreasing the ACN concentration from 5 to 2% during sample loading. Hydrophilic
      peptides were the main contributors to the increase in peptide identifications
      and, at higher ACN concentrations, were washed from the precolumn during
      desalting. Sampling of the hydrophilic peptides was enhanced by using a shallow
      initial ACN gradient. The results were found to be resin-specific and not
      generalizable. Our investigation demonstrates the often unappreciated importance
      of optimizing sample loading conditions to reflect the aims of the research and
      the characteristics of the LC configurations employed.

PMID- 19601633
TI  - Indole adsorption to a lipid monolayer studied by optical second harmonic
      generation.
AB  - Adsorption of indole from an aqueous subphase to a lipid (DPPC) monolayer at the
      air/water interface is studied by nonresonant second harmonic generation (SHG)
      with lambda = 800 nm and by observation of compression isotherms with a Langmuir
      trough. The nonlinear susceptibilities of the monolayers have been carefully
      measured, including corrections for the contributions of the lipid monolayer and
      subphase, calibration of absolute values by comparison with a quartz reference,
      and measurement of absolute phase by comparison with a clean air/water interface.
      Details of the calibrations involving z-cut quartz and the clean air/water
      interface are presented. The number density of adsorbed indole molecules has been
      estimated by comparison of nonlinear susceptibilities with a reference monolayer
      of hexadecyl 3-indoleacetate. The extent of adsorption of indole to the lipid
      monolayer is maximum at low surface pressure, decreasing from an indole/DPPC
      ratio near 2:1 as the monolayer is compressed. The free energy change for
      adsorption of indole to the monolayer is estimated as -8.1 kcal/mol, which is
      similar to a result reported previously for a lipid bilayer. Information on the
      orientation of adsorbed indole is derived by comparison of observed ratios of
      nonlinear susceptibilities with calculated ratios for model indole monolayers
      with assumed orientational distributions. Measurement and analysis procedures are
      described in detail for effective nonlinear susceptibilities in a s/p
      polarization basis. The calculations use as input the molecular
      hyperpolarizability tensor of indole, which is obtained by using several
      computational approaches including sum-over-states calculations and time
      dependent Hartree-Fock and density functional methods. The analysis shows that
      the pyrrole ring of indole points toward the water subphase, and the tilt angle
      of the long axis of indole increases from near 50 degrees to near 60 degrees as
      the monolayer is compressed. The analysis also suggests that the plane of indole
      lies more nearly parallel than perpendicular to the plane of the interface.

PMID- 19601634
TI  - Photoelectron spectrum of ammonia, a test case for the calculation of Franck
      Condon factors in molecules undergoing large geometrical displacements upon
      photoionization.
AB  - The vibrational structure of the photoelectron spectrum of ammonia, the simplest
      molecule undergoing a large displacement of its equilibrium geometry upon
      photoionization, is analyzed by evaluating the Franck-Condon integrals at the
      anharmonic level of approximation. It is shown that if the rectilinear Cartesian
      representation of normal modes is adopted Duschinsky's transformation yields a
      too large displacement of the bond distance coordinate, with the appearance of
      several progressions which are not observed in the experimental spectrum. This
      apparent failure is completely corrected by the inclusion of anharmonic couplings
      between the principal active mode, the out of plane bending of the planar cation,
      and the totally symmetric stretching mode, leading to a satisfying reproduction
      of the observed spectrum and to a more convincing assignment of the weaker
      progression observed in the high-resolution spectrum.

PMID- 19601635
TI  - A general procedure to functionalize agglomerating nanoparticles demonstrated on
      nanodiamond.
AB  - Upon reduction of particle size to the nanometer range, one has to deal with the
      general issue of spontaneous agglomeration, which often obstructs postsynthesis
      modification of nanoparticle surfaces. A technique to cope with this phenomenon
      is required to realize a wide variety of applications using nanoparticles in
      solvents or as refined assemblies. In this article, we report on a new technique
      to facilitate surface chemistry of nanoparticles in a conventional glassware
      system. A beads-assisted sonication (BASD) process was examined to break up
      persistent agglomerates of nanodiamonds in two different reactions for
      simultaneous surface functionalization. The chosen reactions are the silanization
      with an acrylate-modified silane and the arylation using diazonium salts. The
      BASD process can be successfully applied even where the original material is not
      dispersible in the reaction solvent at all, as the formation of ever smaller,
      increasingly functionalized agglomerates is improving their solubility. We have
      confirmed that the presence of ceramic beads enables functionalization of each
      primary particle, while conventional magnetic stirring or beadless sonication can
      reach primary particles only when agglomeration is loose. Additionally,
      mechanical surface modification of nanodiamond was found to take place by BASD
      with high energy density, leading to sp(2)-hybridized surface patches on
      nanodiamond. This allowed for the efficient grafting of aryl groups to the
      surface of primary diamond nanoparticles. Stable, homogeneously functionalized
      nanodiamond particles in colloidal solution can be obtained by this method.

PMID- 19601636
TI  - Colloidal silicon nanorod synthesis.
AB  - The colloidal synthesis of crystalline silicon (Si) nanorods with diameters of 5
      to 10 nm and lengths of 15 to 75 nm is demonstrated. Trisilane was decomposed in
      a hot solvent in the presence of dodecylamine and gold (Au) nanocrystals.
      Nanorods form by Au-seeded solution-liquid-solid growth with dodecylamine serving
      as capping ligands that stabilize the nanorod dispersion. Post-synthesis etching
      of the Au seeds from the nanorod tips is also demonstrated.

PMID- 19601637
TI  - 50 nm DNA nanoarrays generated from uniform oligonucleotide films.
AB  - One of the most challenging but potentially rewarding goals in nanoscience is the
      ability to direct the assembly of nanoscale materials into functional
      architectures with high yields, minimal steps, and inexpensive procedures.
      Despite their unique physical properties, the inherent difficulties of
      engineering wafer-level arrays of useful devices from nanoscale materials in a
      cost-effective manner have provided serious roadblocks toward technological
      impact. To address nanoscale features while still maintaining low fabrication
      costs, we demonstrate here an inexpensive printing method that enables repeated
      patterning of large-area arrays of nanoscale materials. DNA strands were
      patterned over 4 mm areas with 50 nm resolution by a soft-lithographic
      subtraction printing process, and DNA hybridization was used to direct the
      assembly of sub-20 nm materials to create highly ordered two-dimensional
      nanoparticle arrays. The entire printing and assembly process was accomplished in
      as few as three fabrication steps and required only a single lithographically
      templated silicon master that could be used repeatedly. The low-cost procedures
      developed to generate nanoscale DNA patterns can be easily extended toward roll
      to-roll assembly of nanoscale materials with sub-50 nm resolution and fidelity.

PMID- 19601638
TI  - The methoxylated flavones eupatorin and cirsiliol induce CYP1 enzyme expression
      in MCF7 cells.
AB  - Flavonoids have often been associated with cancer prevention and activity of the
      human cytochrome P450 enzymes CYP1A1 and CYP1B1 with the occurrence of cancer.
      The flavones eupatorin (1) and cirsiliol (2) enhanced CYP1 enzyme activity in a
      concentration-dependent manner in MCF7 human breast adenocarcinoma cells. In the
      range of 0-2.5 microM, 2 caused a dose-dependent increase in CYP1B1 mRNA levels
      and an increase in CYP1A1 mRNA. Compound 1 caused an increase in CYP1A1 and
      CYP1B1 mRNA at higher doses (approximately 5 microM). Both CYP1B1 and CYP1A1
      catalyzed the conversion of 2 into an as yet unidentified compound. Application
      of the CYP1 family inhibitor, acacetin, significantly increased the IC(50) value
      of 2 in MCF7 cells, but did not significantly affect the action of 1. The data
      suggest that 2 induces CYP1 enzyme expression in cancer cells and is subsequently
      converted by CYP1B1 or CYP1A1 into an antiproliferative agent.

PMID- 19601639
TI  - A simple method to determine electrospray response factors of noncovalent
      complexes.
AB  - The quantitative study of noncovalent complexes by electrospray mass spectrometry
      requires the determination of the relative response of each species. The method
      proposed here to determine the electrospray response factors is based on the use
      of (1) an internal standard and (2) the mass balance equation applied to one
      binding partner M, for which different complexes M(x)L(y) are detected in the
      electrospray mass spectra. A set of experiments providing various ratios between
      the complexes (e.g., different ligand concentrations in a titration experiment or
      different time points in a kinetics experiment) is used to generate a set of
      independent linear equations that can be solved using simple matrix algebra to
      find the response factors of each M(x)L(y) complex relative to that of the
      internal standard. The response factors can then be used to determine equilibrium
      dissociation constants or for the quantitative monitoring of reaction kinetics.
      The first is illustrated with a study of DNA-ligand complexes, where we show that
      neither minor groove binding nor intercalation dramatically affects the DNA
      response factor. The second is illustrated with a study of the association
      kinetics of the telomeric G-quadruplex dGGG(TTAGGG)(3) with its complementary
      strand, where the response factors allow correcting for the relative response of
      the quadruplex and the long duplex and obtaining reproducible association rate
      constants independently of the source tuning potentials.

PMID- 19601640
TI  - TAT peptide and its conjugates: proteolytic stability.
AB  - The proteolytic cleavage of TATp, TATp-PEG(1000)-PE conjugate (TATp-conjugate),
      and TATp as TATp-conjugate in mixed micelles made of TATp-conjugate and PEG(5000)
      PE (2.5% mol of TATp-conjugate, TATp-Mic) were studied by HPLC with fluorescent
      detection using fluorenylmethyl chloroformate (FMOC) labeling and by MALDI-TOF MS
      analysis. The cleavage kinetics were analyzed in human blood plasma and in
      trypsin-containing phosphate buffered saline (PBS), pH 7.4, to simulate the
      proteolytic activity of human plasma. The trypsinolysis of free TATp, TATp
      conjugate, and TATp-Mic revealed that the main initial fragmentation is an
      endocleavage at the carboxyl terminus resulting in an Arg-Arg (RR) dimer. The
      trypsinolysis followed pseudo-first-order kinetics. The cleavage of the free TATp
      was relatively fast with a half-life of a few minutes (t(1/2) ~ 3.5 min). The
      TATp-conjugate showed more stability with about a 3-fold increase in half-life
      (t(1/2) ~ 10 min). TATp in TATp-Mic was highly protected against proteolysis with
      an over 100-fold increase in half-life (t(1/2) ~ 430 min). The shielding of TATp
      by PEG moieties in the proposed TATp-Mic is of great importance for its potential
      use as a cell-penetrating moiety for multifunctional "smart" drug delivery
      systems with detachable PEG.

PMID- 19601641
TI  - Byproduct with altered fluorescent properties is formed during standard
      deprotection step of hexachlorofluorescein labeled oligonucleotides.
AB  - HEX-labeled oligonucleotides obtained via typical synthetic protocols may contain
      more than 15% of material with altered spectral characteristics. We discovered
      hexachlorofluorescein residue transformation unknown earlier for standard DNA
      ammonolysis step. HEX residue reacts with ammonium hydroxide yielding acridine
      derivative, which has differed UV-VIS and fluorescent properties compared to HEX.
      Therefore, for critical bioassays where sensitivity and/or fluorescent signal
      differentiation (e.g., in quantitative or multiplexed assays) are essential, the
      careful RP-HPLC purification step is required.

PMID- 19601642
TI  - Immobilization and release of the redox mediator ferrocene monocarboxylic acid
      from within cross-linked p(HEMA-co-PEGMA-co-HMMA) hydrogels.
AB  - Cross-linked hydrogels are synthesized from hydroxyethylmethacrylate (HEMA),
      polyethyleneglycol methacrylate (PEGMA), and N-[tris(hydroxymethyl)methyl]
      acrylamide (HMMA) [p(HEMA-co-PEGMA-co-HMMA) hydrogels] containing 1, 3, 5, 7, 9,
      or 12 M % of the cross-linker tetraethyleneglycol diacrylate (TEGDA) and are
      loaded during synthesis with the well-known redox mediator, ferrocene
      monocarboxylic acid (FcCOOH). In the absence of FcCOOH, the M% TEGDA in deionized
      (DI) water (48%; 1 mol % TEGDA to 32%; 12 mol % TEGDA) scales with the cross-link
      density in accordance with Flory-Huggins-Rehner theory. The release profiles of
      FcCOOH from hydrogel slabs (43.0 mM) into 0.1 M HEPES/0.1 M KCl buffer are
      determined from the oxidation peak current of FcCOOH via cyclic voltammetry (100
      mV/s) and are decidedly Fickian with overall diffusion coefficients that range
      from 2.64 x 10(-8) cm(2)/s (1 mol % TEGDA) to 4.87 x 10(-9) cm(2)/s (12 mol %
      TEGDA) and with n parameters that approximated 0.5 but nonetheless linearly
      declined from 0.49 (1 mol %) to 0.42 (12 mol %). Diffusion coefficients, like
      hydration, strongly correlate with the M% TEGDA and hence with the cross-link
      density or the molecular weight (MW) between cross-links. The temperature
      dependence of the release profiles measured at 10, 15, 20, 25, 30, 35, 40, and 45
      degrees C reveal thermally activated transport with activation energies that are
      30 kJ/mol (3 mol %), 36 kJ/mol (5 mol %), 45 kJ/mol (7 mol %), 47 kJ/mol (9 mol
      %) and 57 kJ/mol (12 mol %). Covalent tethering of the FcCOOH via the UV
      polymerizable monomers ferrocene monomethacrylate (Fc-AEMA) and ferrocene
      polyethylene glycol monomethacrylate (Fc-PEG(3500)-AEMA) to produce pendant redox
      moieties is shown to eliminate or attenuate release of Fc. While, Fc-AEMA showed
      no evidence of release (0%) from the hydrogel, its PEG-conjugated equivalent, Fc
      PEG(3500)-AEMA, shows release of 16% Fc after 5 days of immersion. These
      hydrogels will serve as the immobilization matrix for oxidoreductase enzymes of
      biosensors and the parameters obtained used in the modeling of such systems.

PMID- 19601643
TI  - 4'-Demethylnobiletin, a bioactive metabolite of nobiletin enhancing PKA/ERK/CREB
      signaling, rescues learning impairment associated with NMDA receptor antagonism
      via stimulation of the ERK cascade.
AB  - The biochemical and pharmacological activities of nobiletin, including
      neurotrophic and memory-enhancing action, in both in vitro and in vivo systems
      are well established. However, whether its metabolites do have such beneficial
      effects like nobiletin remains to be examined. Here we, for the first time,
      report that 2-(4-hydroxy-3-methoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one (4'
      demethylnobiletin), a major metabolite of nobiletin identified in the urine of
      rats and mice, stimulates the phosphorylation of ERK and CREB and enhances CRE
      mediated transcription by activating a PKA/MEK/ERK pathway, like nobiletin, in
      cultured hippocampal neurons. Since NMDA receptor-mediated ERK signaling is
      involved in memory processing, including associative memories, we also examined
      whether 4'-demethylnobiletin, by activating ERK signaling, could restore learning
      impairment. Chronic intraperitoneal (ip) treatment of the mice with 10 or 50 mg
      of 4'-demethylnobiletin/kg rescued the NMDA receptor antagonist MK-801-induced
      learning impairment, accompanied by improvement of the MK-801-induced decrease in
      the level of ERK phosphorylation in the hippocampus of the animals. Consistently,
      4'-demethylnobiletin also restored MK-801-induced inhibition of NMDA-stimulated
      phosphorylation of not only ERK but also PKA substrates in cultured rat
      hippocampal neurons. Moreover, we actually detected 4'-demethylnobiletin in the
      brain of mice following acute ip administration, demonstrating that the
      metabolite can cross the blood-brain barrier to reach the brain and thereby exert
      its effects to reverse learning impairment. Therefore, these results suggest that
      4'-demethylnobiletin, a bioactive metabolite of nobiletin, may serve as a
      potential therapeutic agent, at least, for memory disorders associated with a
      dysregulated NMDA receptor ERK signaling, like nobiletin.

PMID- 19601644
TI  - Hydrogels cross-linked by native chemical ligation.
AB  - We describe the use of native chemical ligation (NCL) reaction to covalently
      cross-link soluble polymers into hydrogels. Macromonomers consisting of a four
      armed poly(ethylene glycol) (PEG) core end-functionalized with either thioester
      or N-terminal cysteine peptide were designed and synthesized. Upon mixing aqueous
      solutions of the thioester and N-terminal cysteine macromonomers, rigid hydrogels
      formed within minutes. The gelation time was affected by choice of buffer, pH,
      polymer concentration, reaction temperature, and chemical composition of the N
      terminal cysteine conjugate. The kinetics of gel formation and the viscoelastic
      behavior of selected hydrogels were further studied by oscillatory rheology,
      which demonstrated a minimum gel formation time of approximately two minutes and
      the formation of an elastic cross-linked hydrogel via the NCL reaction. A useful
      feature of this hydrogel strategy is the regeneration of thiol functional groups
      as a result of the NCL reaction, thereby allowing functionalization of the
      polymer hydrogel with biomolecules. This was demonstrated by conjugation of a
      maleimide-GRGDSPG-NH(2) peptide to an NCL hydrogel, permitting the attachment of
      human mesenchymal stem cells (hMSCs) on the hydrogel. Due to the mild reaction
      conditions, chemoselectivity, and potential for biological functionalization, our
      approach may prove useful as a general method for hydrogel formation, including
      hydrogels intended for biomedical applications.

PMID- 19601645
TI  - Biosynthesis of salinosporamides from alpha,beta-unsaturated fatty acids:
      implications for extending polyketide synthase diversity.
AB  - A new series of coenzyme A-tethered polyketide synthase extender units were
      discovered in relation to the biosynthesis of the salinosporamide family of
      anticancer agents from the marine bacterium Salinispora tropica. In vivo and in
      vitro experiments revealed that the crotonyl-CoA reductase/carboxylase SalG has
      broad substrate tolerance toward 2-alkenyl-CoAs that give rise to the
      salinosporamide C-2 substitution pattern.

PMID- 19601647
TI  - Structural basis of serine/threonine phosphatase inhibition by the archetypal
      small molecules cantharidin and norcantharidin.
AB  - The inhibition of a subgroup of human serine/threonine protein phosphatases is
      responsible for the cytotoxicity of cantharidin and norcantharidin against tumor
      cells. It is shown that the anhydride rings of cantharidin and norcantharidin are
      hydrolyzed when bound to the catalytic domain of the human serine/threonine
      protein phosphatases 5 (PP5c), and the high-resolution crystal structures of PP5c
      complexed with the corresponding dicarboxylic acid derivatives of the two
      molecules are reported. Norcantharidin shows a unique binding conformation with
      the catalytically active Mn2PP5c, while cantharidin is characterized by a double
      conformation in its binding mode to the protein. Different binding modes of
      norcantharidin are observed depending of whether the starting ligand is in the
      anhydride or in the dicarboxylic acid form. All these structures will provide the
      basis for the rational design of new cantharidin-based drugs.

PMID- 19601648
TI  - Synthesis and preliminary in vitro biological evaluation of 4-[(4
      hydroxyphenyl)sulfanyl]but-3-en-2-one, a 4-mercaptophenol derivative designed as
      a novel bifunctional antimelanoma agent.
AB  - We report the synthesis and preliminary in vitro biological evaluations of 4-[(4
      hydroxyphenyl)sulfanyl]but-3-en-2-one, a compound designed as a potential
      bifunctional antimelanoma agent, bearing both a tyrosinase-activatable phenolic
      moiety and a GSH-reactive alpha,beta-unsaturated carbonyl group. Both the E (1)
      and Z (2) isomers of the synthesized compound proved to be very good substrates
      of mushroom tyrosinase, reacted quickly with GSH at physiological pH, and showed
      a significant cytotoxic activity against B16F1 murine melanoma cells.

PMID- 19601649
TI  - Protein hydrogen exchange measured at single-residue resolution by electron
      transfer dissociation mass spectrometry.
AB  - Because of unparalleled sensitivity and tolerance to protein size, mass
      spectrometry (MS) has become a popular method for measuring the solution hydrogen
      (1H/2H) exchange (HX) of biologically relevant protein states. While incorporated
      deuterium can be localized to different regions by pepsin proteolysis of the
      labeled protein, the assignment of deuteriums to individual residues is typically
      not obtained, thereby limiting a detailed understanding of HX and the dynamics of
      protein structure. Here we use gas-phase fragmentation of peptic peptides by
      electron transfer dissociation (ETD) to measure the HX of individual amide
      linkages in the amyloidogenic protein beta2-microglobulin. A comparison of the
      deuterium levels of 60 individual backbone amides of beta2-microglobulin measured
      by HX-ETD-MS analysis to the corresponding values measured by NMR spectroscopy
      shows an excellent correlation. The deuterium labeling pattern of beta2
      microglobulin is retained in the gaseous fragment ions by employing mild
      declustering conditions for electrospray ionization. A recently developed model
      peptide is used to arrive at such ion source declustering conditions that prevent
      the occurrence of intramolecular gas-phase hydrogen (1H/2H) migration (i.e.,
      hydrogen scrambling). This article demonstrates that ETD can be implemented in a
      mass spectrometric method to monitor the conformational dynamics of proteins in
      solution at single-residue resolution.

PMID- 19601650
TI  - Near-infrared spectroscopic study on guest-host interactions among G0-G7 amine
      terminated poly(amidoamine) dendrimers and porous silica materials for
      simultaneously determining the molecular weight and particle diameter by
      multivariate calibration techniques.
AB  - The guest-host interactions of poly(amidoamine) (PAMAM) dendrimers and porous
      silica surfaces were investigated by near-infrared (NIR) diffuse reflection
      spectroscopy. G0-G7 of amine-terminated PAMAM (PAMAM-NH2) dendrimers were
      analyzed comprising early, mid, and late generations. For early stages, the
      adsorption process of the partly protonated dendrimers to the negatively charged
      silica surface strongly depends on the size/shape characteristics of the guest
      (PAMAM-NH2 dendrimers) and host (porous silica) materials. G0-G4 (15-45 A) show
      smaller particle sizes than the pore diameter of the silica (60 A) and thus have
      access to the interior surface of the host material. For mid and later stages (G5
      G7; 54-81 A) only low amounts of the dendrimers adsorb to the silica surface due
      to the inaccessibility to the interior surface. The loading capacity of the
      silica material with adsorbed PAMAM-NH(2) was evaluated by means of capillary
      zone electrophoresis (CZE), whereas deviations from the theoretical to the
      effective particle size and molecular weight (MW) was determined by gas-phase
      electrophoretic mobility molecular analysis (GEMMA) and matrix-assisted laser
      desorption/ionization linear time-of-flight mass spectrometry (MALDI-lin TOF-MS).
      Deviations from the theoretical to the actual values showed a maximum of 13.8%
      and 28.0% for the particle size and MW, respectively. The NIR absorption spectra
      show a distinct band at 4932 cm(-1) (nu(sym) (NH) + amide II) due to the adsorbed
      dendrimers. It was found that the absorbance tends to increase with decreasing
      generation number. On this basis multivariate calibration was performed with the
      theoretical data and the data obtained by GEMMA and MALDI-lin TOF-MS. All in all,
      the calculated partial least-squares regression (PLSR) model containing the
      GEMMA/MALDI-lin TOF-MS reference values showed better results than the models
      exclusively calculated from the theoretical values. This indicates that the
      theoretical values do not imply the structural imperfections arising during the
      synthesis that may be present in the PAMAM-NH2 dendrimers.

PMID- 19601651
TI  - Writing droplets of molecularly imprinted polymers by nano fountain pen and
      detecting their molecular interactions by surface-enhanced Raman scattering.
AB  - Molecularly imprinted polymer (MIP) droplets were printed using a pipet or a nano
      fountain pen on surface-enhanced Raman scattering (SERS)-active surfaces, to
      directly monitor the uptake and release of a template molecule, the beta-blocking
      drug propranolol, by SERS. The monitored SERS bands can be related to the
      template, allowing for its detection but also identification in the MIP. This is
      an advantage if the technique is to be used during the development phase of MIPs
      as microstructures, but equally for the readout of MIP-based biochips.

PMID- 19601652
TI  - Macroporous materials as novel catalysts for efficient and controllable
      proteolysis.
AB  - A novel nanopore based digestion strategy has been developed by directly adding a
      macroporous material as catalyst to the conventional in-solution reaction system.
      Without increasing the enzyme or protein concentrations, this simple digestion
      approach exhibits high proteolysis efficiency and selectivity due to the in situ
      fast adsorption of both enzymes and proteins from bulk solution into the
      macropores of the catalysts, where the target substrates and enzymes are greatly
      concentrated and confined in the nanospace to realize a quick digestion. Based on
      the electrostatic interaction matching between the biomolecules and catalysts,
      selective extraction and digestion of proteins with different isoelectric points
      can be achieved by adjusting the surface charge of the catalysts. This nanoporous
      reaction system has been successfully applied to the analysis of a complex
      biological sample, where 293 proteins are identified, while only 100 proteins are
      obtained by the standard overnight in-solution digestion. The present nanospace
      confined digestion strategy will lead to promising advances not only in
      proteomics but also in other applications where enzymatic reactions are involved.

PMID- 19601654
TI  - Novel approach to the elemental analysis of crude and diesel oil.
AB  - A novel approach to the elemental analysis of crude and diesel oil permitted
      preconcentration of trace elements is presented. An oil sample is continuously
      pumped through the rotating coil column as a mobile phase while an aqueous nitric
      acid solution is retained as a stationary phase. Two phases are kept well mixed
      and agitated but there is no emulsion on the interface at chosen conditions.
      Preliminary investigation of features of stationary phase retention of two-phase
      liquid systems (oil/oil products-aqueous solution) in rotating coil column has
      been shown. Special features of CCC give an opportunity to vary the volume of oil
      samples to be analyzed from 10 mL to 1 L or more. Trace metals are
      preconcentrated into 10 mL of stationary aqueous acidic phase which pumped out of
      the column for analysis can be easily determined with inductively coupled plasma
      mass spectrometry (ICP-MS) without additional sample preparation. Optimal
      concentration in the stationary phase of nitric acid for preconcentration of
      elements from oil by CCC has been investigated. Combination of CCC with ICP-MS
      gives the possibility to develop a rapid, reliable and accurate method of trace
      metal including rare earth elements (REE) determination in crude oils and oil
      products. Combination of preconcentration method by CCC and highly sensitive
      determination method (ICP-MS) for quantitative detection of the trace elements
      (without any additional sample preparation) has been suggested for the first
      time.

PMID- 19601653
TI  - Product length, dye choice, and detection chemistry in the bead-emulsion
      amplification of millions of single DNA molecules in parallel.
AB  - The amplification of millions of single molecules in parallel can be performed on
      microscopic magnetic beads that are contained in aqueous compartments of an oil
      buffer emulsion. These bead-emulsion amplification (BEA) reactions result in
      beads that are covered by almost-identical copies derived from a single template.
      The post-amplification analysis is performed using different fluorophore-labeled
      probes. We have identified BEA reaction conditions that efficiently produce
      longer amplicons of up to 450 base pairs. These conditions include the use of a
      Titanium Taq amplification system. Second, we explored alternate fluorophores
      coupled to probes for post-PCR DNA analysis. We demonstrate that four different
      Alexa fluorophores can be used simultaneously with extremely low crosstalk.
      Finally, we developed an allele-specific extension chemistry that is based on
      Alexa dyes to query individual nucleotides of the amplified material that is both
      highly efficient and specific.

PMID- 19601655
TI  - Culturing aerobic and anaerobic bacteria and mammalian cells with a microfluidic
      differential oxygenator.
AB  - In this manuscript, we report on the culture of anaerobic and aerobic species
      within a disposable multilayer polydimethylsiloxane (PDMS) microfluidic device
      with an integrated differential oxygenator. A gas-filled microchannel network
      functioning as an oxygen-nitrogen mixer generates differential oxygen
      concentration. By controlling the relative flow rate of the oxygen and nitrogen
      input gases, the dissolved oxygen (DO) concentration in proximal microchannels
      filled with culture media are precisely regulated by molecular diffusion. Sensors
      consisting of an oxygen-sensitive dye embedded in the fluid channels permit
      dynamic fluorescence-based monitoring of the DO concentration using low-cost
      light-emitting diodes. To demonstrate the general utility of the platform for
      both aerobic and anaerobic culture, three bacteria with differential oxygen
      requirements (E. coli, A. viscosus, and F. nucleatum), as well as a model
      mammalian cell line (murine embryonic fibroblast cells (3T3)), were cultured.
      Growth characteristics of the selected species were analyzed as a function of
      eight discrete DO concentrations, ranging from 0 ppm (anaerobic) to 42 ppm (fully
      saturated).

PMID- 19601656
TI  - Determination of potassium in red blood cells using unmeasured volumes of whole
      blood and combined sodium/potassium-selective membrane electrode measurements.
AB  - Recent studies suggest that the measurement of intracellular potassium
      concentrations in red blood cells (RBC-K) can be a marker for assessing the risk,
      development, and treatment of hypertension. In this work, the combined use of
      miniature potassium- and sodium-selective membrane electrodes is evaluated as a
      simple means to determine RBC-K. The proposed method requires two separate sets
      of electrode measurements: (i) potassium and sodium concentrations in the plasma
      phase of an unmeasured volume of a whole blood sample, and (ii) determination of
      potassium and sodium concentrations in the same sample of blood after complete
      hemolysis by ultrasonic disruption of the RBC membranes. The dilution of sodium
      concentration after hemolysis can be used to determine hematocrit (Hct) (volume
      of red cells per unit volume of blood) of the blood. The concentration of
      potassium within the red blood cells (RBCs) is then calculated using the measured
      change in potassium levels before and after RBCs lysis and the hematocrit level
      determined from the sodium electrode measurements and/or a conventional
      centrifugation method. Good correlation for RBC-K between the proposed method and
      traditional flame photometry is observed for animal blood samples that possess
      the range of potassium levels found within human RBCs (80-120 mM). However, when
      potassium is much lower than that found in human RBCs (known to occur for certain
      animal species), the Hct measured by the sodium electrode method is falsely low,
      compared to traditional spun hematocrit values, because of an increased level of
      sodium within the RBCs, necessitating use of spun Hct levels to assess RBC-K
      accurately. It is envisioned that this new approach could be further miniaturized
      into a single-use disposable cartridge type electrode system that would enable
      rapid point-of-care screening of RBC-K levels in human subjects.

PMID- 19601659
TI  - Comparison of major phenolic constituents and in vitro antioxidant activity of
      diverse Kudingcha genotypes from Ilex kudingcha, Ilex cornuta, and Ligustrum
      robustum.
AB  - A total of seven Kudingcha genotypes from three plant species (Ilex kudingcha,
      Ilex cornuta, and Ligustrum robustum) with different geographic origins in China
      were investigated for their major phenolic compounds, individual and total
      phenolics contents, and in vitro antioxidant properties (ABTS, DPPH, FRAP, and OH
      assays). LC-PDA-APCI-MS analysis showed that Kudingcha genotypes from Ilex and
      Ligustrum had entirely different phenolic profiles. Major phenolics in Kudingcha
      genotypes from two Ilex species were mono- and dicaffeoylquinic acids, whereas
      those in a Kudingcha genotype from Ligustrum were phenylethanoid and
      monoterpenoid glycosides. All Kudingcha genotypes of Ilex exhibited significantly
      stronger antioxidant capacities than that of Ligustrum. Within six Ilex
      genotypes, great variation existed in their composition of individual phenolic
      compounds and their antioxidant properties. The comparative data and LC
      fingerprints obtained in this study may provide useful information for screening
      and breeding of better Kudingcha genotypes and also for their authentication and
      quality control.

PMID- 19601658
TI  - Release of liposomal contents by cell-secreted matrix metalloproteinase-9.
AB  - Liposomes have been widely used as a drug delivery vehicle, and currently, more
      than 10 liposomal formulations are approved by the Food and Drug Administration
      for clinical use. However, upon targeting, the release of the liposome
      encapsulated contents is usually slow. We have recently demonstrated that
      contents from appropriately formulated liposomes can be rapidly released by the
      cancer-associated enzyme matrix metalloproteinase-9 (MMP-9). Herein, we report
      our detailed studies to optimize the liposomal formulations. By properly
      selecting the lipopeptide, the major lipid component, and their relative amounts,
      we demonstrate that the contents are rapidly released in the presence of cancer
      associated levels of recombinant human MMP-9. We observed that the degree of
      lipid mismatch between the lipopepides and the major lipid component profoundly
      affects the release profiles from the liposomes. By utilizing the optimized
      liposomal formulations, we also demonstrate that cancer cells (HT-29) which
      secrete low levels of MMP-9 failed to release a significant amount of the
      liposomal contents. Metastatic cancer cells (MCF7) secreting high levels of the
      enzyme rapidly release the encapsulated contents from the liposomes.

PMID- 19601657
TI  - The influence of repair pathways on the cytotoxicity and mutagenicity induced by
      the pyridyloxobutylation pathway of tobacco-specific nitrosamines.
AB  - Tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and
      N'-nitrosonornicotine, are considered to be human carcinogens. Both compounds are
      metabolized to pyridyloxobutylating intermediates that react with DNA to form
      adducts such as 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine, O(2)-[4-(3-pyridyl)-4
      oxobut-1-yl]cytosine, O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxythymidine (O(2)
      pobdT), O(6)-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine (O(6)-pobdG), and 4
      hydroxy-1-(3-pyridyl)-1-butanone-releasing adducts. The role of specific DNA
      adducts in the overall genotoxic activity of the pyridyloxobutylation pathway is
      not known. One adduct, O(6)-pobdG, is mutagenic. To characterize the mutagenic
      and cytotoxic properties of pyridyloxobutyl DNA adducts, the impact of DNA repair
      pathways on the cytotoxic and mutagenic properties of the model
      pyridyloxobutylating agent, 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNKOAc), was investigated in Chinese hamster ovary cell lines proficient or
      deficient in O(6)-alkylguanine DNA alkyltransferase (AGT), deficient in both AGT
      and base excision repair (BER), or deficient in both AGT and nucleotide excision
      repair (NER). The repair of the four pyridyloxobutyl DNA adducts was determined
      in the same cell lines via sensitive LC-MS/MS methods. NNKOAc was more cytotoxic
      in the cell lines lacking AGT, BER, and NER repair pathways. It also induced more
      mutations in the hprt gene in the BER- and NER-deficient cell lines. However, AGT
      expression did not influence NNKOAc's mutagenicity despite efficient repair of
      O(6)-pobdG. Analysis of the hprt mutational spectra indicated that NNKOAc
      primarily caused point mutations at AT base pairs. GC to AT transition mutations
      were a minor contributor to the overall mutation spectrum, providing a rationale
      for the observation that AGT does not protect against the overall mutagenic
      properties of NNKOAc in this model system. The only adduct affected by the
      absence of effective NER was O(2)-pobdT. Slower repair of O(2)-pobdT in NER
      deficient cells was associated with increased AT to TA transversion mutations,
      supporting the hypothesis that these mutations are caused by O(2)-pobdT.
      Together, these data support a hypothesis that the pyridyloxobutylation pathway
      generates multiple mutagenic and toxic adducts.

PMID- 19601660
TI  - Attenuation of renoinflammatory cascade in experimental model of diabetic
      nephropathy by sesamol.
AB  - Diabetes has become the most common single cause of end-stage renal disease
      (ESRD) in the United States and Europe. Approximately 30-40% of patients with
      type I and 15% with type II diabetes mellitus develop end ESRD. The study was
      designed to evaluate the impact of sesamol on renal function and renoinflammatory
      cascade in streptozotocin (STZ)-induced diabetes. STZ-induced diabetic rats were
      treated with sesamol (2, 4, and 8 mg/kg/day; po) or with vehicle from the fifth
      to eighth weeks. After 8 weeks, urine albumin excretion, urine output, serum
      creatinine, blood urea nitrogen, creatinine, and urea clearance were measured.
      Cytoplasmic and nuclear fractions of kidney were prepared for the quantification
      of oxidative-nitrosative stress (lipid peroxidation, superoxide dismutase,
      catalase, nonprotein thiols, total nitric oxide), tumor necrosis factor-alpha
      (TNF-alpha), tissue growth factor-1 beta (TGF-beta1), p65 subunit of NFkappabeta,
      and caspase-3. After 8 weeks of STZ injection, the rats produced significant
      alteration in renal function, increased oxidative-nitrosative stress, TNF-alpha,
      TGF-beta1, caspase-3 activity in cytoplasmic lysate, and active p65 subunit of
      NFkappabeta in nuclear lysate of kidney of diabetic rats. Interestingly, co
      administration of sesamol significantly and dose-dependently prevented
      biochemical and molecular changes associated with diabetes. Moreover, diabetic
      rats treated with insulin-sesamol combination produced more pronounced effect on
      molecular parameters as compared to their respective groups. The data reveal that
      sesamol modulates the release of profibrotic cytokines, oxidative stress, ongoing
      chronic inflammation, and apoptosis and thus exerts a marked renoprotective
      effect.

PMID- 19601661
TI  - A green process for producing biodiesel from feather meal.
AB  - This paper describes a new and environmentally friendly process for developing
      biodiesel from commercial feather meal, a waste product of the poultry industry.
      Currently, feather meal is used as an animal feed, given its high protein
      content, and also as a fertilizer because of its high nitrogen content. In this
      work, we have extracted fat from the feather meal in boiling water (70 degrees C)
      and then transesterified the fat into biodiesel using KOH and methanol; 7-11%
      biodiesel (on a dry basis) is produced in this process. ASTM analysis of the
      prepared feather meal biodiesel confirmed that the biodiesel is of good quality
      and comparable to other biodiesels made from other common feedstocks. Given the
      amount of feather meal produced by the poultry industry, it is estimated that
      this process can create 150-200 million gallons of biodiesel in the United States
      and 593.2 million gallons worldwide.

PMID- 19601662
TI  - Supramolecular structure and conformation of a (1-->3)(1-->2)-beta-D-glucan from
      Lactobacillus suebicus CUPV221 as observed by tapping mode atomic force
      microscopy.
AB  - Tapping mode atomic force microscopy (TM-AFM) has been used to analyze the
      supramolecular structure and conformation of the (1-->3)(1-->2)-beta-D-glucan
      produced by Lactobacillus suebicus CUPV221 isolated from cider. Solutions for TM
      AFM observation were prepared by dispersing the solid glucan in distilled water
      and in alkaline aqueous solutions. It was found that from the distilled water at
      10 mg/L or higher concentrations, the (1-->3)(1-->2)-beta-D-glucan forms
      networks. The heat resistance of the networks depends on the concentration. From
      the alkaline aqueous solutions, different supramolecular structures were observed
      depending on the pH. From the weakest alkaline solution, a fairly rough
      morphology with a high density of spikelike growth features was revealed. As the
      ionic force of the medium increased, the sizes of the spikelike growth features
      diminished, and even many disaggregated fibers could be found. At 0.4 M NaOH (pH
      13.16), the aggregates had disappeared almost totally. NaOH aqueous solutions
      (0.1 and 0.4 M) were used to carry out the study of conformation. At 0.1 M NaOH,
      the aggregates were partially detached, and many free microfibers were found to
      which a helical conformation could be assigned due to their stiffness and rodlike
      character. At 0.4 M NaOH, the beginning of the dissociation of the helical
      structures was seen.

PMID- 19601664
TI  - Clp and RpfF up-regulate transcription of pelA1 gene encoding the major pectate
      lyase in Xanthomonas campestris pv. campestris.
AB  - Exopolysaccharide and several extracellular enzymes of Xanthomonas campestris pv.
      campestris (Xcc), the causative agent of black rot in crucifers, are virulence
      determinants. In this study, two Xcc annotated extracellular pectate lyase genes,
      pelA1 and pelA2, belonging to family 1 of the polysaccharide lyase, were
      characterized. Sequence and mutational analyses have demonstrated that pelA1
      encodes the major pectate lyase, whereas pelA2 is not transcribed. Using the 5'
      RACE method, the pelA1 transcription initiation site was mapped at nucleotide G,
      103 nt upstream of the pelA1 start codon. Promoter analysis demonstrated that
      polygalacturonic acid and CaCl(2) induce the expression of pelA1. Transcriptional
      fusion assays also indicated that Clp (cAMP receptor protein-like protein) and
      RpfF (an enoyl-CoA hydratase homologue that is required for the synthesis of cis
      11-methyl-2-dodecenoic acid, a low molecular weight diffusible signal factor,
      DSF) positively regulate pelA1 transcription. Gel retardation assays showed that
      Clp exerts a positive control over expression of pelA1 by direct binding to the
      upstream Clp-binding site. In conclusion, the present research demonstrated that
      pelA1 codes for the major pectate lyase in Xcc strain Xc17 and that its
      expression is up-regulated by Clp and RpfF. This is the first study to
      characterize pectate lyase gene expression in Xcc.

PMID- 19601663
TI  - Expression analysis identifies FAD2-2 as the olive oleate desaturase gene mainly
      responsible for the linoleic acid content in virgin olive oil.
AB  - The effect of ripening stage and water regimen on oleate desaturase gene
      expression levels in the fruit of different olive ( Olea europaea L.) varieties
      was investigated to elucidate the contribution of each to the linoleic acid
      content in virgin olive oil. To this end, fatty acid analysis and quantitative
      real time PCR were performed using distinct olive tissues and different
      developmental stages from the Picual and Arbequina cultivars. The results showed
      that the olive FAD2-1, FAD2-2, and FAD6 genes were spatial and temporally
      regulated. In addition, the data indicated that FAD2-2 seems to be the main gene
      responsible for the linoleic acid content in the olive fruit mesocarp tissue.
      This conclusion was also confirmed when the study was extended to Hojiblanca,
      Picudo, and Manzanilla varieties. With regard to the water regimen, unlike the
      Picual cultivar, a small increase of linoleic acid was observed in the Arbequina
      variety cultivated with irrigation, which correlated well with the increase
      detected for the FAD2-2 gene expression level. All of these data strongly suggest
      that FAD2-2 is the main gene that determines the linoleic acid content in the
      virgin olive oil.

PMID- 19601665
TI  - Production and physicochemical properties of recombinant Lactobacillus plantarum
      tannase.
AB  - Tannase is an enzyme with important biotechnological applications in the food
      industry. Previous studies have identified the tannase encoding gene in
      Lactobacillus plantarum and also have reported the description of the
      purification of recombinant L. plantarum tannase through a protocol involving
      several chromatographic steps. Here, we describe the high-yield production of
      pure recombinant tannase (17 mg/L) by a one-step affinity procedure. The purified
      recombinant tannase exhibits optimal activity at pH 7 and 40 degrees C. Addition
      of Ca(2+) to the reaction mixture greatly increased tannase activity. The
      enzymatic activity of tannase was assayed against 18 simple phenolic acid esters.
      Only esters derived from gallic acid and protocatechuic acid were hydrolyzed. In
      addition, tannase activity was also assayed against the tannins tannic acid,
      gallocatechin gallate, and epigallocatechin gallate. Despite L. plantarum tannase
      representing a novel family of tannases, which shows no significant similarity to
      tannases from fungal sources, both families of enzymes shared similar substrate
      specificity range. The physicochemical characteristics exhibited by L. plantarum
      recombinant tannase make it an adequate alternative to the currently used fungal
      tannases.

PMID- 19601666
TI  - Technological steps and yeast biomass as factors affecting the lipid content of
      beer during the brewing process.
AB  - Knowledge of lipid content and composition in the brewing process enables the
      quality control of the final product. Lipids have a beneficial effect on yeast
      growth during fermentation as well as deleterious effects on end-product quality.
      The lipid content of a beer affects its ability to form a stable head of foam and
      plays an important role in beer staling. Lipid oxidation during wort production
      is of great interest because of its effect on beer quality: both lipids and their
      oxidation products are known to have adverse effects on beer flavor, whereas
      interactions between lipids and protein films stabilizing the gas bubbles are
      thought to cause the collapse of foam. In this background, the aim of this
      research was the characterization of the lipid content during a brewing process
      for evaluating the influence of both technological steps and yeast biomass in the
      lipid composition of beer. Lipid contents and their fatty acid profile were
      evaluated in brewing raw materials, wort, and beer. A high-resolution gas
      chromatography-flame ionization detector (HRGC-FID) system was used for fatty
      acid determination in lipid extracts. The results of the present study
      highlighted that the main technological steps influencing the lipid content in
      brewing byproduct and beer were clarification in a whirlpool and filtration.
      Moreover, the presence of metabolically active yeast cells (used as starter
      culture) were found to have a great influence on the fatty acids composition of
      lipids.

PMID- 19601667
TI  - Influence of genetic and environmental factors on selected nutritional traits of
      Triticum monococcum.
AB  - To evaluate the effect of genotype, year, and location on protein, lipid, tocol,
      and lutein content and on fatty acids composition of wholemeal flour, five
      einkorns (Triticum monococcum L. ssp. monococcum) and one control bread wheat
      were cropped in Italy for two years in four different locations. Genotype and
      year exerted major effects on protein, tocotrienol, and lutein contents, while
      tocopherol and lipid contents were influenced only by the genotype. The
      concentrations of linoleic, oleic, and palmitic acids (the most abundant among
      the 14 fatty acids identified), as well as of saturated (SFA), monosaturated
      (MUFA), and polyunsaturated (PUFA) fatty acids, differed between einkorns and
      control and, to some extent, years were constant across locations.
      Notwithstanding the environmental variation, all einkorns consistently showed
      higher protein (on average, +59%), lipid (+50%), tocotrienol (+88%), total tocol
      (+46%), lutein (+483%), and MUFA (+53%) content, along with lower SFA (-21%) and
      PUFA (-8%) than the bread wheat control.

PMID- 19601668
TI  - Design, synthesis, and bioactivity study of novel benzoylpyridazyl ureas.
AB  - A series of novel benzoylpyridazyl ureas were designed and synthesized from
      maleic anhydride and hydrazine monohydrate. These benzoylureas were identified by
      (1)H NMR spectroscopy and element analysis. The bioactivities of the new
      compounds were evaluated. These compounds exhibited larvicidal activities against
      oriental armyworm, and in particular, compound 13 displayed comparable activity
      to the commercial insecticide Hexaflumuron. Most of these compounds also had some
      larvicidal activities against mosquito. Interestingly, some compounds showed good
      plant growth regulatory activities.

PMID- 19601669
TI  - Volatile compounds of red wines macerated with Spanish, American, and French oak
      chips.
AB  - The volatile composition of a red wine aged for 2 months with three different
      Spanish oak chips (Quercus pyrenaica and Quercus petraea) from different regions
      of Castilla y Leon was compared with that of wines aged with American and French
      chips. In general, the extraction kinetics showed that the maximum concentration
      of the volatile compounds extracted from wood can be reached in only 1 month. In
      the final wines, the levels of furanic aldehydes and eugenol were higher in the
      wines macerated with Spanish chips, whereas cis-whiskey-lactone, vanillin, and
      methyl vanillate showed higher levels in wines treated with American chips. Among
      the wines treated with the different Spanish chips, the differences observed in
      the volatile composition were more related to the geographical origin of the
      forest than to the botanical species. In general, the wines macerated with
      Spanish chips showed levels of oak-related volatile compounds that were more
      similar to those macerated with French chips than to those macerated with
      American chips.

PMID- 19601670
TI  - Influence of growth regulators in biomass production and volatile profile of in
      vitro plantlets of Thymus vulgaris L.
AB  - In vitro shoots of thyme (Thymus vulgaris L.) were established, and the effects
      of the auxin indole-3-acetic (IAA) acid and the cytokinins benzyladenine (BA),
      zeatin (ZEA), and kinetin (KIN) at 1.0, 5.0, and 10.0 microM on rooting, biomass
      production, and volatile compounds production by these plants were investigated.
      The volatiles were extracted by solid phase microextraction (SPME) and analyzed
      by gas chromatography. The highest biomass shoot growth was obtained with BA at
      5.0 microM, while IAA at all concentrations tested achieved 100% rooting
      frequency. The three major compounds were gamma-terpinene (22.8-38.8%), p-cymene
      (13.8-27.9%), and thymol (6.5-29.0%). Quantitative changes of these compounds
      were observed in response to the effect of varying growth regulators
      concentrations in the culture medium. Growing Thymus vulgaris L. plants in media
      supplemented with IAA at 1.0 microM increased volatile compounds such as thymol
      by 315%. Nevertheless, the same major compounds were produced in all treatments
      and no qualitative changes were observed in the volatile profile of thyme plants.

PMID- 19601671
TI  - Synergy effect of sodium acetate and glycosidically bound volatiles on the
      release of volatile compounds from the unscented cut flower (Delphinium elatum L.
      "Blue Bird").
AB  - Many modern floricultural varieties have lost their scent during traditional
      breeding programs. The factors that result in the nonscent emission of some cut
      flowers remain unclear. The objective of this study was to investigate whether
      the nonscent emission is due to one of the factors, the lack of suitable
      substrates (or precursors of scent compounds). Using solid-phase microextraction
      and dynamic headspace volatile sampling techniques, the supplement of nonvolatile
      compounds such as 2-coumaric acid glucoside to the unscented cut flower such as
      Delphinium elatum L. "Blue Bird" enhanced the emission of scent from the flower,
      which was sufficient for detection by the human olfaction. Interestingly,
      compared with feeding with each compound, the combination of sodium acetate and 2
      coumaric acid glucoside showed the synergy effect on enhancement of coumarin, a
      cherry leaf-like scent emission from the flower, which is due to one of factors
      that sodium acetate enhanced the activity of beta-glucosidase being involved in
      the formation of the scent compound. These results suggest that some enzymes
      responsible for the formation of floral scents indeed occur in the unscented
      flowers such as Delphinium elatum L. "Blue Bird", and the non- or low-scent
      emission of the flowers are due to the lack of suitable substrates.

PMID- 19601672
TI  - Effects of phenolic compounds on the browning of cooked barley.
AB  - Barley grain products undergo browning when cooked. To evaluate effects of
      phenolic compounds on browning, various amounts of (+)-catechin,
      proanthocyanidins, or related phenolic compounds were added to aqueous barley
      extracts or barley pastes, which were heated at 90 degrees C for 1 or 2 h,
      respectively. In barley extract, (+)-catechin, procyanidin B3 (PCB3),
      prodelphinidin B3 (PDB3), and a trimer of gallocatechin-gallocatechin-catechin
      (PDT1) dose-dependently elevated absorbance at 420 nm after heating. PDB3 caused
      browning faster than PCB3 and (+)-catechin. In barley paste, PDB3 and PDT1
      decreased the L* value and increased the a* and b* values of the paste dose
      dependently after heating and PCB3 and (+)-catechin did so to a lesser extent.
      Caffeic acid promoted the browning in both of the extract and paste, while
      protocatechuic acid, eriodictyol, and (+)-taxifolin promoted it in the extract
      and myricetin and quercetin promoted it in the paste. Compounds promoting
      browning have catechol or pyrogallol structures in common.

PMID- 19601673
TI  - Metabolite profiling of two novel low phytic acid (lpa) soybean mutants.
AB  - A GC-based approach was applied to compare the metabolite profiles of two low
      phytic acid (lpa) soybean mutants and their respective wild-types. The lpa
      mutants (Gm-lpa-TW75-1 and Gm-lpa-ZC-2) were grown together with the wild-types
      (Taiwan 75 and Zhechun no. 3) in three and four field trials, respectively. HPLC
      analysis revealed a phytic acid reduction of -53% for Gm-lpa-TW75-1 and of -46%
      for Gm-lpa-ZC-2. For Gm-lpa-TW75-1, no accumulation of lower inositol phosphates
      was observed, whereas Gm-lpa-ZC-2 exhibited significantly increased contents of
      the lower inositol phosphates InsP(3), InsP(4), and InsP(5) compared to the
      corresponding wild-type. The metabolite profiling revealed that compared to the
      wild-types, 40% (Gm-lpa-TW75-1) and 21% (Gm-lpa-ZC-2) of the detected peaks were
      statistically significantly different in the lpa mutants grown at one field
      trial. However, the majority of these differences were shown to be related to
      environmental impact and natural variability rather than to the mutation event.
      Identification of consistent metabolic changes in the lpa mutants revealed
      decreased contents of myo-inositol, galactinol, raffinose, stachyose, and the
      galactosyl cyclitols galactopinitol A, galactopinitol B, and fagopyritol B1
      compared to the wild-type. These consistently pronounced changes in Gm-lpa-TW75-1
      confirmed the suggested mutation target. Consideration of the metabolic changes
      observed for Gm-lpa-ZC-2 (accumulation of lower inositol phosphates and increased
      myo-inositol contents) indicated a mutation event affecting the latter
      biosynthetic steps leading to phytic acid. The study demonstrated the
      applicability of metabolite profiling for the detection of changes in the
      metabolite phenotype induced by mutation breeding and its power in assisting in
      the elucidation of mutation events.

PMID- 19601674
TI  - Chiral separation of catechins in buckwheat groats and the effects of phenolic
      compounds in mice subjected to restraint stress.
AB  - This paper investigates the stereochemistry of catechin and epicatechin compounds
      in buckwheat ( Fagopyrum esculentum Moench) groats and then examines the effects
      of an orally administered mixture of the phenolic compounds isolated from the
      groats in restrained mice. Phenolic compounds separated by Sephadex LH-20
      chromatography contained catechin and epicatechin compounds with a sugar moiety
      or esterified with phenolic acid derivatives along with rutin. Other unidentified
      major compounds in the HPLC chromatogram were also deduced on the basis of the
      spectrometric data with LC-MS/MS analysis to be catechin or epicatechin
      compounds. A chiral HPLC separation technique under normal-phase conditions
      showed that catechin and its derivative compounds in buckwheat groats were (+)
      isomers, whereas epicatechin and its derivative compounds were (-)-isomers.
      Propylene glycol (PPG) or buckwheat groats phenolic compounds (BGP) in PPG (10 or
      100 mg/kg of body weight) were administered intragastrically once per day for 3
      days to mice, which were then restrained for 24 h. Unrestrained mice were given
      PPG solution with or without free access to feed and water. Restraint stress
      induced an elevation in plasma arteriosclerotic index, hepatic total cholesterol,
      and the amount of thiobarbituric acid-reactive substances (TBARS) in plasma and
      liver tissues. In contrast, these variables were suppressed in the restrained
      mice that were given BGP. These results suggest that BGP has in vivo antistress
      effects against the reactions induced by immobilization in mice.

PMID- 19601675
TI  - Lack of evidence for antiatherogenic effects of wheat bran or corn bran in
      apolipoprotein E-knockout mice.
AB  - Epidemiological studies have suggested that intake of whole grains is inversely
      associated with coronary artery disease. The mechanisms, however, are not
      completely clear. We tested the hypothesis that intake of wheat bran or corn bran
      would (1) increase the plasma concentration of phenolic antioxidants and (2)
      reduce atherosclerosis in apo E-knockout mice. Apo E-knockout (E-KO) mice were
      fed for 18 weeks with a 0.1% cholesterol-supplemented diet in the absence of
      grain brans or the presence of 1.7% yellow dent corn bran or 3.3% hard red spring
      wheat bran. The concentration of antioxidant ferulic acid in plasma and urine was
      measured by HPLC to monitor the bioavailability of grain phenolics. Plasma
      lipoprotein profiles were determined by a combination of HPLC and online
      enzymatic methods. Urinary 15-isoprostane F(2t), an in vivo LDL oxidation
      biomarker, and atherosclerotic lesions were analyzed by ELISA and histological
      methods, respectively. Dietary supplementation with corn or wheat bran resulted
      in a 4- and 24-fold increase, respectively, in urinary excretion of ferulic acid.
      The urinary recovery rate of ferulic acid from the two brans in apo E-KO mice was
      approximately 1.9-2.9%. Dietary corn bran but not wheat bran also significantly
      increased the concentration of total ferulic acid in plasma. Nevertheless, the
      supplementation with either bran product for 18 weeks did not significantly alter
      the urinary excretion of 15-isoprostane F(2t), change the lipoprotein profiles,
      nor reduce the atherosclerotic lesion development in this animal model. The
      results suggest that phenolic antioxidants from the two types of bran may not be
      sufficient to reduce atherosclerosis in this animal model.

PMID- 19601676
TI  - Preventive effect of a melon extract rich in superoxide scavenging activity on
      abdominal and liver fat and adipokine imbalance in high-fat-fed hamsters.
AB  - Studies showed that dietary antioxidants could be a therapy against obesity that
      is associated with a state of oxidative stress. Thus, this paper investigates
      whether a dietary ingredient, a melon juice extract rich in superoxide dismutase,
      would prevent the development of such obesity in hamsters. Five groups received a
      standard diet or a high-fat diet (HF) plus a daily gavage with water (control) or
      extract at 0.7, 2.8, or 5.6 mg/day. After 84 days, the higher dose lowered
      triglyceridemia (68%), production of liver superoxide anion (12%), mitochondrial
      cytochrome c oxidase activity (40%), lipid and protein oxidation products (35 and
      35%, respectively), and leptinemia (99%) and increased adiponectinemia (29%),
      leading to a concomitant reduction in insulinemia (39%), insulin resistance
      (41%), and abdominal lipids (25%). The extract triggered a remarkable decrease of
      liver lipids (73%) and fully prevented the steatohepatitis induced by the HF
      diet. Chronic consumption of this melon extract may represent a new alternative
      to reduce obesity induced by a high-fat diet.

PMID- 19601677
TI  - Apoptotic effects of protocatechuic acid in human breast, lung, liver, cervix,
      and prostate cancer cells: potential mechanisms of action.
AB  - Apoptotic effects of protocatechuic acid (PCA) at 1, 2, 4, 8 micromol/L on human
      breast cancer MCF7 cell, lung cancer A549 cell, HepG2 cell, cervix HeLa cell, and
      prostate cancer LNCaP cell were examined. Results showed that PCA concentration
      dependently decreased cell viability, increased lactate dehydrogenase leakage,
      enhanced DNA fragmentation, reduced mitochondrial membrane potential, and lowered
      Na(+)-K(+)-ATPase activity for these cancer cells (P < 0.05). PCA also
      concentration-dependently elevated caspase-3 activity in five cancer cells (P <
      0.05), but this agent at 2-8 micromol/L significantly increased caspase-8
      activity (P < 0.05). PCA concentration-dependently decreased intercellular
      adhesion molecule level in test cancer cells (P < 0.05) but significantly
      inhibited cell adhesion at 2-8 micromol/L (P < 0.05). PCA also concentration
      dependently lowered the levels of interleukin (IL)-6 and IL-8 in five cancer
      cells (P < 0.05), but this agent at 2-8 micromol/L significantly suppressed
      vascular endothelial growth factor production (P < 0.05). These findings suggest
      that PCA is a potent anticancer agent to cause apoptosis or retard invasion and
      metastasis in these five cancer cells.

PMID- 19601678
TI  - Formation of [Ru(NHC)4(eta(2)-O2)H]+: an unusual, high frequency hydride chemical
      shift and facile, reversible coordination of O2.
AB  - Reaction of the purple tetrakiscarbene ruthenium cation
      [Ru(I(i)Pr(2)Me(2))(4)H](+) (1, I(i)Pr(2)Me(2) = 1,3-diisopropyl-4,5
      dimethylimidazol-2-ylidene) with oxygen affords the pink eta(2)-O(2) hydride
      species [Ru(I(i)Pr(2)Me(2))(4)(eta(2)-O(2))H](+) (2). 2 displays (i) a very
      facile, reversible O(2) coordination and (ii) an unexpectedly positive hydride
      chemical shift, and both these features can be predicted and explained by density
      functional theory (DFT) calculations.

PMID- 19601680
TI  - Metal-directed synthesis of enantiomerially pure dimetallic lanthanide
      luminescent triple-stranded helicates.
AB  - The synthesis and photophysical evaluation of two enatiomerially pure dimetallic
      lanthanide luminescent triple-stranded helicates is described. The two systems,
      formed from the chiral (R,R) ligand 1 and (S,S) ligand 2, were produced as single
      species in solution, where the excitation of either the naphthalene antennae or
      the pyridiyl units gave rise to Eu(III) emission in a variety of solvents.
      Excitation of the antennae also gave rise to circularly polarized Eu(III)
      luminescence emissions for Eu(2):1(3) and Eu(2):2(3) that were of equal intensity
      and opposite sign, confirming their enantiomeric nature in solution providing a
      basis upon which we were able to assign the absolute configurations of Eu(2):1(3)
      and Eu(2):2(3).

PMID- 19601679
TI  - Formation of protocell-like vesicles in a thermal diffusion column.
AB  - Many of the properties of bilayer membranes composed of simple single-chain
      amphiphiles seem to be well-suited for a potential role as primitive cell
      membranes. However, the spontaneous formation of membranes from such amphiphiles
      is a concentration-dependent process in which a significant critical aggregate
      concentration (cac) must be reached. Since most scenarios for the prebiotic
      synthesis of fatty acids and related amphiphiles would result in dilute solutions
      well below the cac, the identification of mechanisms that would lead to increased
      local amphiphile concentrations is an important aspect of defining reasonable
      conditions for the origin of cellular life. Narrow, vertically oriented channels
      within the mineral precipitates of hydrothermal vent towers have previously been
      proposed to act as natural Clusius-Dickel thermal diffusion columns, in which a
      strong transverse thermal gradient concentrates dilute molecules through the
      coupling of thermophoresis and convection. Here we experimentally demonstrate
      that a microcapillary acting as a thermal diffusion column can concentrate a
      solution of oleic acid. Upon concentration, self-assembly of large vesicles
      occurs in regions where the cac is exceeded. We detected vesicle formation by
      fluorescence microscopy of encapsulated dye cargoes, which simultaneously
      concentrated in our channels. Our findings suggest a novel means by which simple
      physical processes could have led to the spontaneous formation of cell-like
      structures from a dilute prebiotic reservoir.

PMID- 19601681
TI  - Preparation and crystal growth of Na24Si136.
AB  - The synthesis and single crystal growth of clathrate-II Na(24)Si(136) is
      performed in one step applying the spark plasma treatment to the precursor
      Na(4)Si(4). The reported results demonstrate a new route to intermetallic
      compounds facilitated by the electric field and current. SPS is revealed to offer
      significant opportunities as a novel preparatory method for synthesis and crystal
      growth of solid state materials.

PMID- 19601682
TI  - Resonance chemical imaging of polythiophene/fullerene photovoltaic thin films:
      mapping morphology-dependent aggregated and unaggregated C=C Species.
AB  - Resonance Raman spectroscopic imaging is introduced as a physical probe to
      identify and spatially map morphology-dependent variations of intra- and
      interchain interactions and order in poly-3-hexylthiophene (P3HT) and [6,6]
      phenyl-C(61)-butyric acid methyl ester (PCBM) photovoltaic blend thin films.
      Absorption spectra and C=C symmetric stretching Raman modes of P3HT/PCBM blend
      films show contributions from two distinct species that are assigned as
      aggregated and unaggregated P3HT chains with characteristic Raman frequencies of
      approximately 1450 (I(C=C)(agg)) and approximately 1470 cm(-1) (I(C=C)(un)),
      respectively. Upon thermal annealing of blend films, the relative concentrations
      of I(C=C)(agg) and I(C=C)(un) species (R = I(C=C)(agg)/I(C=C)(un)) changes on
      average from 0.79 +/- 0.20 (as-cast) to 2.45 +/- 0.77 (annealed). It is proposed
      that R values report on the relative densities of states (DOS) of aggregated and
      unaggregated species, and resonance Raman imaging is then used to spatially map
      morphology-dependent variations of R values and uncover subclassifications of
      these species. From both R and frequency dispersion resonance Raman images of
      I(C=C)(agg) and I(C=C)(un) species, four distinct types of P3HT chains are
      identified and mapped in annealed P3HT/PCBM blend thin films: (i) highly
      aggregated/crystalline, (ii) partially aggregated, (iii) interfacial, and (iv)
      unaggregated/PCBM rich. The change in aggregation upon annealing is attributed to
      an increase in planarity of the P3HT chains that is determined from the ratios of
      C=C/C-C symmetric stretching mode intensities.

PMID- 19601683
TI  - Characterization of dispersed heteropoly Acid on mesoporous zeolite using solid
      state 31P NMR spin-lattice relaxation.
AB  - Dispersion and quantitative characterization of supported catalysts is a grand
      challenge in catalytic science. In this paper, heteropoly acid H(3)PW(12)O(40)
      (HPA) is dispersed on mesoporous zeolite silicalite-1 derived from hydrothermal
      synthesis using carbon black nanoparticle templates, and the catalytic activity
      is studied for 1-butene isomerization. The HPAs supported on conventional zeolite
      and on mesoporous zeolite exhibit very different activities and thus provide good
      model systems to investigate the structure dependence of the catalytic
      properties. The HPA on mesoporous silicalite-1 shows enhanced catalytic activity
      for 1-butene isomerization, while HPA on conventional silicalite-1 exhibits low
      activity. To elucidate the structural difference, supported HPA catalysts are
      characterized using a variety of techniques, including (31)P magic angle spinning
      nuclear magnetic resonance, and are shown to contain a range of species on both
      mesoporous and conventional zeolites. However, contrary to studies reported in
      the literature, conventional NMR techniques and chemical shifts alone do not
      provide sufficient information to distinguish the dispersed and aggregated
      surface species. The dispersed phase and the nondispersed phase can only be
      unambiguously and quantitatively characterized using spin-lattice relaxation NMR
      techniques. The HPA supported on mesoporous zeolite contains a fast relaxation
      component related to the dispersed catalyst, giving a much higher activity, while
      the HPA supported on conventional zeolite has essentially only the slow
      relaxation component with very low activity. The results obtained from this work
      demonstrate that the combination of spinning sideband fitting and spin-lattice
      relaxation techniques can provide detailed structural information on not only the
      Keggin structure for HPA but also the degree of dispersion on the support.

PMID- 19601685
TI  - Homoconjugation/homoaromaticity in main group inorganic molecules.
AB  - Quantum chemical computations show that three groups of inorganic ions and
      neutral molecules, whose structures have long been known and characterized, are
      aromatic due to through-space homoconjugation: (i) I(4)(2+), S(6)N(4)(2+), and
      S(2)I(4)(2+) dications and the (O(2))(4) cluster with pericyclic transition-state
      like (PTS-like) homoaromaticity; (ii) the bishomoaromatic Te(6)(2+) and 1,5
      diphosphadithiatetrazocines; and (iii) the spherically homoaromatic Te(6)(4+).
      The S(2)I(4)(2+) dication has an unusually high S-S bond order (approximately
      2.3) and dual PTS-like aromaticity arising from two separate sets of four-center,
      six-electron (4c-6e) in-plane through-space conjugation. The diamagnetic
      (O(2))(4) structural unit recently observed in epsilon-phase oxygen solid has
      quadruple PTS-like aromaticity, each arising from 4c-6e in-plane through-space
      conjugation within an O(2)-O(2) plane. Finally, we note that the lighter S(6)(4+)
      and Se(6)(4+) homologues of Te(6)(4+) also are spherically homoaromatic and might
      be observable in complexes.

PMID- 19601684
TI  - Structure-activity relationships among random nylon-3 copolymers that mimic
      antibacterial host-defense peptides.
AB  - Host-defense peptides are natural antibiotics produced by multicellular organisms
      to ward off bacterial infection. Since the discovery of these molecules in the
      1980s, a great deal of effort has been devoted to elucidating their mechanisms of
      action and to developing analogues with improved properties for possible
      therapeutic use. The vast majority of this effort has focused on materials
      composed of a single type of molecule, most commonly a peptide with a specific
      sequence of alpha-amino acid residues. We have recently shown that sequence
      random nylon-3 copolymers can mimic favorable properties of host-defense
      peptides, and here we document structure-activity relationships in this polymer
      family. Although the polymers are heterogeneous in terms of subunit order and
      stereochemistry, these materials display structure-activity relationships
      comparable to those that have been documented among host-defense peptides and
      analogous synthetic peptides. Previously such relationships have been interpreted
      in terms of a specific and regular folding pattern (usually an alpha-helix), but
      our findings show that these correlations between covalent structure and
      biological activity do not require the adoption of a specific or regular
      conformation. In some cases our observations suggest alternative interpretations
      of results obtained with discrete peptides.

PMID- 19601686
TI  - Coordination assemblies of [Mn4] single-molecule magnets linked by photochromic
      ligands: photochemical control of the magnetic properties.
AB  - To achieve reversible photoswitching of the magnetic properties of single
      molecule magnets (SMMs), coordination assemblies of a mixed valence tetranuclear
      [Mn(II)(2)Mn(III)(2)] complex linked by open- and closed-ring isomers of a
      photochromic diarylethene ligand were synthesized: [Mn(4)(hmp)(6)(dae
      o)(2)(ClO(4))(2)] x 6 H(2)O (open-ring form; 1o) and [Mn(4)(hmp)(6)(dae
      c)(2)(H(2)O)(2)](ClO(4))(2) x CH(3)CN x 4 H(2)O (closed-ring form; 1c), where
      Hhmp is 2-hydroxymethylpyridine, and H(2)dae-o and H(2)dae-c are open- and closed
      ring isomers of 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene
      (H(2)dae), respectively. From X-ray crystallographic analyses, 1o and 1c have one
      dimensional (1-D) chain structures with a repeating unit of [-{Mn(4)}-(dae)-], in
      which the [Mn(4)] units are bridged by the diarylethene ligands coordinated to
      the Mn(II) sites via carboxylate groups. Magnetic measurements involving direct
      current (dc) and alternating-current (ac) techniques showed that each [Mn(4)]
      cluster in the 1-D chains had an S(T) = 9 ground state due to two kinds of
      intracluster ferromagnetic exchange interactions and behaved as SMMs. Both 1o and
      1c underwent photochromic reactions in the crystalline phase, and their colors
      reversibly changed between reddish-brown and blue upon irradiation with
      ultraviolet (UV) and visible light. For 1o, no significant change in the magnetic
      properties was observed after the photocyclization of the dae-o moiety by UV
      irradiation. In contrast, the photocycloreversion of the dae-c moiety by visible
      irradiation enhanced inter-[Mn(4)] unit interactions in 1c, which was triggered
      by the geometrical change in the diarylethene moiety during the photoreaction and
      the subsequent change in the inter-[Mn(4)] arrangement between the neighboring 1
      D chains. This work illustrates the usefulness of photochromic molecules for
      photoswitching the magnetic behavior of complexes, even superparamagnetic
      systems, with SMM units.

PMID- 19601687
TI  - Contemporary management strategies for fibromyalgia.
AB  - A roundtable meeting that comprised clinical, patient advocacy, and managed care
      experts discussed issues regarding the diagnosis and management of fibromyalgia.
      The panel agreed that earlier diagnosis and treatment, additional education for
      the medical community, and appropriate management by health plans, including
      patient access to US Food and Drug Administration-approved fibromyalgia
      medications, are needed. In addition, physicians, payers, and patient advocates
      must work to improve clinical, economic, and quality-of-life outcomes for
      fibromyalgia patients. Finally, treatment and diagnostic guidelines must be
      updated as advances in disease management are made (including approvals of 3 new
      pharmacologic agents), and development of a therapeutic category for
      "fibromyalgia" on payer formularies is needed.

PMID- 19601688
TI  - Clinical considerations for the diagnosis and treatment of ADHD in the managed
      care setting.
AB  - Although symptoms of attention-deficit/ hyperactivity disorder (ADHD) are
      certainly most visible in children, the syndrome persists into adolescence in 40%
      to 70% of cases and into adulthood in 50% or more of cases. Accurate recognition
      of the disorder is clouded by the frequent presence of psychiatric comorbidities.
      Contributing to these challenges, managed care providers in primary care are
      often inexperienced in identifying and treating ADHD in adults because of a lack
      of formalized training. As such, special consideration must be given to each
      individual age group and includes identifying common clinical presentations,
      characterizing the disorder and its comorbidities, applying validated rating
      scales as screening and treatment outcome measures, and individually assessing
      patients' optimal response to determine the best course of therapy.
      Pharmacotherapy is often initiated to target ADHD symptoms with either a
      stimulant medication or nonstimulants. In addition, behavioral interventions are
      often applied to treat comorbidities and associated impairments of ADHD.

PMID- 19601689
TI  - The role of pharmacotherapy and managed care pharmacy interventions in the
      treatment of ADHD.
AB  - Pharmacotherapy plays a primary role in the management of attention
      deficit/hyperactivity disorder (ADHD), despite the availability of effective
      behavioral interventions. Psychostimulants are the most commonly prescribed form
      of pharmacotherapy for patients with ADHD and their benefits in managed care are
      severalfold, leading not only to symptom resolution and improved quality of life
      for patients, but also reduced costs for payers and purchasers. The use of these
      agents requires careful consideration and management by health plan stakeholders
      for optimal effectiveness. Concerns regarding medication adherence, in addition
      to the potential for diversion and abuse of psychostimulants, highlight the
      importance of effective pharmacotherapy management in patients with ADHD.
      Initiatives promoting medication adherence, such as patient/parent education,
      provider follow-up, and adverse effect management, are crucial for ensuring
      treatment success. Once-daily, extended-release formulations of stimulants may
      also contribute to improving medication adherence, as may managed care pharmacy
      interventions such as pharmacy database monitoring.

PMID- 19601690
TI  - ADHD in managed care: an assessment of the burden of illness and proposed
      initiatives to improve outcomes.
AB  - Attention-deficit/hyperactivity disorder (ADHD) often results in persistent
      problems with attention and impulsivity; these problems, in turn, contribute to
      impairments in a wide range of functions that affect academic, social, and
      workplace performance. The chronic and cumulative effects of these difficulties
      can be overwhelming and outline the significant burden of illness associated with
      ADHD, which is realized in diminished quality of life for patients and their
      families and increasing costs or loss of revenue for payers and employers. This
      burden warrants significant consideration and action from managed care
      stakeholders to foster sound clinical practice and optimal care. For example,
      educational interventions and evidence-based tools can be implemented to assist
      providers with accurate diagnosis and more effective treatment. Furthermore,
      extensive data documenting the benefits of pharmacotherapy and provider follow-up
      have demonstrated that initiatives designed to encourage treatment adherence may
      be the best investment for managed care plans seeking to improve outcomes in
      patients with ADHD.

PMID- 19601691
TI  - Stroke prevention: much can be done.

PMID- 19601692
TI  - An examination of economic outcomes associated with misdiagnosis or
      undertreatment of TIA.
AB  - Transient ischemic attack (TIA) is a common cerebrovascular event that is
      associated with a high risk for secondary stroke, possibly higher than stroke
      itself. Nevertheless, a TIA is often described as a "mini-stroke," implying a
      less serious event requiring less urgent treatment. In reality, TIA and
      subsequent secondary stroke are associated with a very high economic burden.
      Cerebrovascular disease is the most financially costly of all major disease
      states, while morbidity and mortality risk is highly elevated in TIA patients.
      TIA is also associated with a very severe quality-of-life burden, which manifests
      both in terms of diminished functional independence and high rates of depression.
      Furthermore, TIA is commonly misdiagnosed and underdiagnosed, often leading to
      inappropriate treatment. More than half of patients who experience TIA are
      undiagnosed, while those who do receive a diagnosis are often offered neither
      diagnostic imaging nor hospital admission. Much of the morbidity and mortality
      associated with TIA and secondary stroke might be avoided by the application of
      timely and appropriate treatment. Clinical data have shown that accelerated
      treatment of TIA during its acute phase is associated with an 80% reduction of
      secondary stroke risk for the following 3 months, the period of greatest risk.

PMID- 19601693
TI  - The burden and management of TIA and stroke in government-funded healthcare
      programs.
AB  - Transient ischemic attack (TIA) and stroke are a common public health problem.
      Stroke is a leading cause of death in the United States, and TIA occurs
      frequently. In the United States it is estimated that there are 780,000 strokes
      and 240,000 TIAs annually. Many TIAs and strokes, however, may go unreported, and
      subclinical ("silent") strokes and undiagnosed stroke and TIA symptoms in the
      community are common. This is of concern because TIA and stroke have evidence
      based treatments to prevent subsequent or recurrent stroke, and access to rapid
      diagnostic and treatment facilities for these conditions has been shown to be
      highly effective to reduce the risk of stroke. Government-funded and managed care
      health initiatives play an important role in the prevention of stroke in TIA and
      stroke patients. Evidence-based guidelines should be incorporated into
      organizational treatment paradigms for these patients. We will discuss general
      concepts about TIA and stroke, emphasize specific issues in relation to TIA and
      stroke in Medicare and Medicaid populations, and provide examples of government
      funded initiatives to improve TIA and stroke diagnosis and treatment.

PMID- 19601694
TI  - The burden and management of TIA and stroke in the Veterans Administration and
      Department of Defense.
AB  - Transient ischemic attack (TIA) and stroke are commonly occurring cerebrovascular
      events that require prompt and appropriate treatment to reduce the risk of
      secondary stroke. The US Department of Veterans Affairs (VA) and the Department
      of Defense constitute 2 large medical systems treating military personnel, both
      active and retired, as well as many of their dependents. In the area of stroke
      and TIA management, the VA in particular has instituted far-reaching measures,
      including those to ensure adherence to clinical treatment guidelines shown to
      produce optimal outcomes in stroke. The result of these measures has been that VA
      patients experience lower morbidity and mortality risk, as well as lower rates of
      stroke-related rehospitalization, than comparable patients treated through
      Medicare and Medicaid and in university hospitals. These successes in part may be
      an advantage derived from a relatively closed system with sufficient
      administrative discipline to maintain clinical guidelines treatment standards. It
      may also be the case that continuity of care in these systems produces better
      outcomes than more fragmentary treatment that may be experienced in the civilian
      realm. In addition, the VA system avoids incentivizing physicians for performing
      medical services, and instead incentivizes quality of care, which may provide a
      further advantage for patients treated within that system.

PMID- 19601696
TI  - Fabrication of porous extracellular matrix scaffolds from human adipose tissue.
AB  - Adipose tissue is found over the whole body and easily obtained in large
      quantities with minimal risk by a common surgical operation, liposuction.
      Although liposuction was originally intended for the removal of undesired adipose
      tissue, it may provide an ideal material for tissue engineering scaffolds. Here
      we present novel, porous scaffolds prepared from human adipose tissues. The
      scaffolds were fabricated in a variety of macroscopic shapes such as round
      dishes, squares, hollow tubes, and beads. The microscopic inner porous structure
      was controlled by the freezing temperature, with a decrease in pore size as the
      freezing temperature decreased. The scaffold prepared from human adipose tissue
      contains extracellular matrix components including collagen. Preliminary in vitro
      studies showed that human adipose-derived stem cells attached to a human
      extracellular matrix scaffold and proliferated. This scaffold based on human
      adipose tissue holds great promise for many clinical applications in regenerative
      medicine, particularly in patients requiring soft-tissue regeneration.

PMID- 19601695
TI  - A three-dimensional gel bioreactor for assessment of cardiomyocyte induction in
      skeletal muscle-derived stem cells.
AB  - Skeletal muscle-derived stem cells (MDSCs) are able to differentiate into
      cardiomyocytes (CMs). However, it remains to be investigated whether
      differentiated CMs contract similar to native CMs. Here, we developed a three
      dimensional collagen gel bioreactor (3DGB) that induces a working CM phenotype
      from MDSCs, and the contractile properties are directly measured as an engineered
      cardiac tissue. Neonate rat MDSCs were isolated from hind-leg muscles via the
      preplate technique. Isolated MDSCs were approximately 60% positive to Sca-1 and
      negative to CD34, CD45, or c-kit antigens. We sorted Sca-1(-) MDSCs and
      constructed MDSC-3DGBs by mixing MDSCs with acid soluble rat tail collagen type-I
      and matrix factors. MDSC-3DGB exhibited spontaneous cyclic contraction by culture
      day 7. MDSC-3DGB expressed cardiac-specific genes and proteins. Histological
      assessment revealed that cardiac-specific troponin-T and -I expressed in a
      typical striation pattern and connexin-43 was expressed similar to the native
      fetal ventricular papillary muscle. beta-Adrenergic stimulation increased MDSC
      3DGB spontaneous beat frequency. MDSC-3DGB generated contractile force and
      intracellular calcium ion transients similar to engineered cardiac tissue from
      native cardiac cells. Results suggest that MDSC-3DGB induces a working CM
      phenotype in MDSCs and is a useful 3D culture system to directly assess the
      contractile properties of differentiated CMs in vitro.

PMID- 19601697
TI  - Switching from concomitant latanoprost 0.005% and timolol 0.5% to a fixed
      combination of travoprost 0.004%/timolol 0.5% in patients with primary open-angle
      glaucoma and ocular hypertension: a 6-month, multicenter, cohort study.
AB  - PURPOSE: To assess the usefulness and tolerability of systematically switching
      glaucoma patients from latanoprost 0.005% and timolol 0.5% (Lat + Tim) to a fixed
      combination of travoprost 0.004%/timolol 0.5% (TTFC), and to record the effects
      of this switch on tear-film break-up time (TBUT). MAIN OUTCOME MEASURES:
      Intraocular pressure (IOP) reduction, patients reaching IOP < 18 mmHg; the rate
      of discontinuation; TBUT; and the onset of adverse events (AEs). METHODS:
      Multicenter, observational cohort, 6-month study: 309 patients on concomitant Lat
      + Tim were switched to TTFC (evening dosage). IOP, TBUT, and AEs were recorded at
      baseline and after 1 and 6 months. RESULTS: IOP was significantly decreased (from
      18.3 +/- 2.9 to 16.6 +/- 2.7 mmHg) after substitution (p < 0.0001). Many patients
      (82%) reached an IOP < 18 mmHg (p < 0.0001). TBUT improved significantly (from
      8.4 +/- 3.6 to 9.2 +/- 3.8 s, p < 0.0001). A few patients reported AEs (8.7%),
      which caused discontinuation in a low percentage (4.5%). CONCLUSION: TTFC
      appeared useful in this selected population. In this study, patients who
      underwent a regimen modification to TTFC obtained further reduction in IOP with a
      lower exposition to preservative toxicity. The low discontinuation rate at 6
      months indicates a good tolerability profile.

PMID- 19601698
TI  - Evidence-based treatment of chronic immune-mediated neuropathies.
AB  - Immune-mediated neuropathies are treatable disorders that can result in
      considerable disability in some cases. Chronic immune-mediated neuropathies
      include chronic inflammatory demyelinating polyradiculoneuropathy, multifocal
      motor neuropathy and neuropathy associated with monoclonal gammopathy. In recent
      years, therapeutic strategies for these disorders have become clearer as a result
      of large, randomized controlled trials. However, the treatments used can have
      serious adverse effects and at least 30% of patients do not respond to
      conventional therapies. The aim of this paper is to review available data on
      evidence-based immunotherapy of chronic immune-mediated neuropathies and to
      summarize recent findings and results obtained with new innovative therapies,
      such as new immunosuppressants and monoclonal antibodies.

PMID- 19601699
TI  - The pharmacological treatment of nystagmus: a review.
AB  - Nystagmus is an involuntary, to-and-fro movement of the eyes that can result in a
      reduction in visual acuity and oscillopsia. Mechanisms that cause nystagmus are
      better understood in some forms, such as acquired periodic alternating nystagmus,
      than in others, for example acquired pendular nystagmus, for which there is
      limited knowledge. Effective pharmacological treatment exists to reduce
      nystagmus, particularly in acquired nystagmus and, more recently, infantile
      nystagmus. However, as there are very few randomized controlled trials in the
      area, most pharmacological treatment options in nystagmus remain empirical.

PMID- 19601700
TI  - The value of irbesartan in the management of hypertension.
AB  - Elevated blood pressure levels are highly prevalent and are a major reason for
      cardiovascular events and thus place a significant financial burden on healthcare
      systems worldwide. Guidelines recommend five first-line anti-hypertensive drug
      classes, but compelling indications may indicate favoring one drug class over
      another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure
      lowering efficacy which is at least comparable with other drug classes, including
      ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics.
      They have, in addition, a lower side effect profile than other drug classes and
      patients on ARBs are more persistent with therapy. Compelling indications for the
      use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy,
      proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation,
      metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a
      high efficacy in lowering blood pressure, which has been shown to be at least
      comparable with ACE-Is and superior to other ARBs such as losartan and valsartan.
      This translated into a better cost-effectiveness for irbesartan than for
      valsartan and losartan in the treatment of hypertension. In addition, irbesartan
      has been shown to be effective in both early and late stage diabetic nephropathy.
      It has further demonstrated considerable cost savings over standard therapy
      including beta-blockers, diuretics and non-dihydropyridine calcium channel
      blockers at all stages of kidney disease. Based on efficacy data from the
      Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non
      insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan
      Study, it has also demonstrated cost savings over losartan in late stage renal
      disease. While both losartan and irbesartan are registered for the treatment of
      late stage diabetic nephropathy, irbesartan is also registered for early stage
      diabetic nephropathy in the EU. In summary, the data from randomized clinical
      trials on the efficacy of antihypertensive drugs provides an indication of their
      real value to patients. In addition observational data from clinical practice and
      proven end-organ protection in diabetic nephropathy provides further evidence of
      the true value of irbesartan compared to other ARBs in the treatment of
      hypertension.

PMID- 19601701
TI  - Ambrisentan, an endothelin receptor type A-selective endothelin receptor
      antagonist, for the treatment of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature
      characterized by vasoconstriction and vascular proliferation, which leads to
      right heart failure and death. Prostacyclin, NO and endothelin are felt to be key
      mediators in the development of PAH. We present the available published and
      presented data about ambrisentan, an ET(A)-selective endothelin receptor
      antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment
      of PAH in patients with WHO functional class II and III symptoms. Randomized,
      placebo-controlled trials have demonstrated a significant improvement in exercise
      capacity and decrease in time to clinical worsening, along with evidence to
      support an improvement in WHO functional class and quality of life for patients
      receiving ambrisentan. Long-term data have shown a 1-year survival of 95%; of the
      survivors, 94% remained on ambrisentan monotherapy. Endothelin receptor
      antagonists as a drug class have previously been associated with peripheral
      edema, aminotransferases abnormalities and a teratogenic risk to a developing
      fetus. Peripheral edema was observed in patients receiving ambrisentan; however,
      a greater percentage was experienced in patients aged > 65 years. In contrast,
      significant aminotransferase abnormalities were not observed with ambrisentan
      treatment in the placebo-controlled trials, and in all clinical trials combined
      the 1-year risk seems to be low (< 3%). Despite these data, the FDA requires
      monthly liver function tests monitoring. As with other ERAs, monthly pregnancy
      testing is required in all women of child bearing potential.

PMID- 19601702
TI  - In vivo acceleration of skin growth using a servo-controlled stretching device.
AB  - Tension is a principal force experienced by skin and serves a critical role in
      growth and development. Optimal tension application regimens may be an important
      component for skin tissue engineering and dermatogenesis. In this study, we
      designed and tested a novel servo-controlled skin-stretching device to apply
      predetermined tension and waveforms in mice. The effects of static and cyclical
      stretching forces were compared in 48 mice by measuring epidermal proliferation,
      angiogenesis, cutaneous perfusion, and principal growth factors using
      immunohistochemistry, real-time reverse transcriptase-polymerase chain reaction,
      and hyperspectral imaging. All stretched samples had upregulated epidermal
      proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain
      reaction of epidermal growth factor, transforming growth factor beta1, and nerve
      growth factor demonstrated greater expression in cyclically stretched skin when
      compared to static stretch. Hypoxia-induced factor 1alpha was significantly
      upregulated in cyclically stretched skin, but poststretch analysis demonstrated
      well-oxygenated tissue, collectively suggesting the presence of transient
      hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by
      mechanotransduction and as a result of repeated cycles of temporary hypoxia.
      Further analysis of mechanotransduction signaling pathways may provide additional
      insight to improve skin tissue engineering methods and optimize our device.

PMID- 19601703
TI  - Opioid switching and rotation in primary care: implementation and clinical
      utility.
AB  - BACKGROUND: Opioid therapy is the standard treatment for moderate-to-severe
      cancer pain and is becoming a more frequent treatment for moderate-to-severe
      chronic noncancer pain. Response to opioids varies significantly between patients
      and even within the individual patient at different stages of treatment. Finding
      an opioid at a dose that provides adequate long-term analgesia with minimal
      adverse effects can be difficult. Opioid switching and opioid rotation, at
      different stages of therapy, represent two clinical strategies used to optimize
      opioid response for patients with moderate-to-severe pain. OBJECTIVES: Review the
      theoretical and clinical evidence supporting the concepts of opioid switching and
      rotation, outline the conditions under which these practices should be
      considered, and briefly suggest practical steps for their implementation. SCOPE:
      Clinical literature, clinical practice and guideline databases, and professional
      society websites were searched for articles or reports describing opioid
      switching or opioid rotation in chronic pain therapy; variability in patient
      response to opioid therapy; physiologic, pharmacologic, and genetic factors that
      affect clinical response to opioids; and practical approaches to maximizing
      analgesia and minimizing adverse effects in opioid therapy. It is outside the
      scope of this review to evaluate the pharmacoeconomic aspects that affect changes
      in opioid therapy. FINDINGS: The variability in de novo clinical response to
      opioids likely represents the interaction of the varying properties of the
      individual opioids with the variability in individual patient biology. This
      interaction forms the rationale for opioid switching and explains its clinical
      utility. As with opioid switching, success with opioid rotation is related to the
      myriad of factors determining an individual patient's response to a specific
      opioid. However, the benefits of opioid rotation also derive from a partial
      reversal of tolerance at the mu-opioid receptor and the response of different
      micro-opioid receptor subtypes to the different opioids.

PMID- 19601704
TI  - Effects of tolterodine ER on patient-reported outcomes in sexually active women
      with overactive bladder and urgency urinary incontinence.
AB  - OBJECTIVE: To assess the effects of tolterodine extended release (ER) on patient
      reported outcomes (PROs) in sexually active women with overactive bladder (OAB)
      and urgency urinary incontinence (UUI). RESEARCH DESIGN AND METHODS: This
      multicenter, double-blind, placebo controlled trial included 411 women aged > or
      =18 years reporting OAB symptoms for > or =3 months; > or =8 micturitions per 24
      hours (including > or =0.6 UUI episodes and > or =3 OAB micturitions) in 5-day
      bladder diaries at baseline, and being in a sexually active relationship for > or
      =6 months. Subjects randomized to placebo or tolterodine ER completed validated
      OAB- or incontinence-specific questionnaires, including the Patient Perception of
      Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency
      Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at
      baseline and week 12, as well as the Perception of Treatment Benefit and
      Treatment Satisfaction questions at week 12. This study is registered with
      ClinicalTrials.Gov (identifier: NCT00143481). RESULTS: The mean age of enrolled
      women was approximately 48 years. Compared with placebo, the tolterodine ER group
      reported significant baseline to week 12 improvements in PPBC responses (p =
      0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and
      HRQL domain scores (all p < 0.05); IIQ Emotional Health domain scores (p < 0.05);
      proportions of subjects reporting treatment benefit (79 vs. 54%; p < 0.0001) and
      satisfaction (78 vs. 59%; p < 0.0001). Improvements on the UPS were not
      significantly different. CONCLUSIONS: Tolterodine ER treatment was associated
      with improvements in multiple OAB- and incontinence-specific PROs in a sexually
      active, relatively young, and racially diverse population of women. The findings
      provide clinicians with new insights into the impact of OAB and its treatment on
      HRQL in this population, which has been underrepresented in previous OAB studies.
      Study limitations include a potential underestimation of the impact of OAB
      symptoms resulting from the exclusion of women who may not be sexually active
      because of their urinary symptoms.

PMID- 19601705
TI  - Predictors of heartburn resolution and erosive esophagitis in patients with GERD.
AB  - OBJECTIVES: The primary objective was to assess gastroesophageal reflux disease
      (GERD) symptom resolution rates with esomeprazole by erosive esophagitis (EE)
      status, and the secondary objective was to evaluate potential predictors of the
      presence of EE and heartburn resolution. BACKGROUND: Patients with GERD who have
      EE have higher reported symptom resolution rates than those with nonerosive
      reflux disease (NERD) when treated with proton pump inhibitors (PPIs). STUDY:
      This open-label multicenter study included adults with GERD symptoms. Patients
      were stratified by EE status after endoscopy and received once-daily esomeprazole
      40 mg for 4 weeks. Questionnaires determined symptom response rates, and baseline
      predictors of EE or heartburn resolution were evaluated. Potential predictors,
      including years with GERD, history of EE, and time to relief with antacids, were
      examined. RESULTS: Heartburn resolution rates at 4 weeks were higher for patients
      with EE than NERD (69% [124/179] vs. 48% [85/177]; p < 0.0001). Multivariate
      models had moderate predictive ability for EE (c-index, 0.76) and poor predictive
      ability (c-index, 0.57) for heartburn resolution. However, faster heartburn
      relief with antacid use, particularly within 15 min, was predictive of EE and
      heartburn resolution. CONCLUSIONS: Patients with EE have higher heartburn
      resolution rates than patients with NERD after treatment, although recall bias
      may be possible. Fast relief with antacid use is predictive of EE and heartburn
      resolution with a PPI and suggests that a history of antacid relief may provide
      corroborative evidence to empiric PPI therapy in determining whether patients
      with heartburn have acid reflux disease. ClinicalTrials.Gov IDENTIFIER:
      NCT00242736.

PMID- 19601706
TI  - Injectable hyaluronan for the treatment of carpometacarpal osteoarthritis: open
      label pilot trial.
AB  - OBJECTIVE: Carpometacarpal osteoarthritis (CMC OA) is highly prevalent in older
      adults, and is often unresponsive to medical treatment. Intra-articular Hylan G-F
      20 has been shown to improve pain and function in patients with knee OA; however,
      its effectiveness in CMC OA is less clear. METHODS: 32 patients with CMC OA were
      injected with Hylan G-F 20, once weekly for three consecutive weeks. Patients
      were assessed 4, 12, 20 and 26 weeks after the first injection. A last-value
      carried forward analysis was performed. RESULTS: Average age was 64 years, (range
      46-79), 69% were female and 97% Caucasian. Fifty-three percent had at least one
      previous corticosteroid injection in the affected CMC joint. At 26 weeks, mean
      visual analogue scale (VAS) for pain had improved significantly (15.2 mm; p-value
      = 0.006). Disabilities of the arm, shoulder and hand questionnaire (DASH) scores
      also improved significantly (12.6; p-value < 0.001). A DASH change of 10-14 is
      considered clinically meaningful. Neither key strength nor opposition grip
      strength improved. VAS scores for pain at 26 weeks showed good correlation with
      patient satisfaction (Spearman r = 0.52, p-value < 0.01). Adverse events
      potentially related to the injections included three episodes of post-injection
      pain and swelling, and one case of crystal proven pseudogout. CONCLUSION: Intra
      articular Hylan G-F 20 injections reduced pain and improved function in patients
      with CMC OA at 26 weeks in this small open label study. Limitations of this study
      include its small, open label design. Larger randomized controlled trials are
      needed to confirm these results, and to determine predictors of response to
      treatment. CLINICAL TRIAL REGISTRATION: This study was approved by the
      Institutional Review Board at the Hospital for Special Surgery, New York, NY, USA
      and registered at (www.ClinicalTrials.Gov)# NCT00198029.

PMID- 19601707
TI  - Antipsychotic switching: results from a one-year prospective, observational study
      of patients with schizophrenia.
AB  - OBJECTIVE: The Health Outcomes of a Canadian Community Cohort (HOCCC) study is a
      1-year prospective observational study of outpatients with schizophrenia or
      related psychotic disorders. The purpose of the study was to compare
      effectiveness of antipsychotic treatment as measured by 1-year treatment
      completion rates. DESIGN AND METHODS: Patients (N = 929) were enrolled if in the
      course of usual clinical practice they switched to a second-generation
      antipsychotic (SGA). Observational data were collected for up to 1 year. The
      primary analysis compared 1-year treatment-completion rates for the olanzapine
      cohort with the other SGA cohort (quetiapine, risperidone, clozapine), using a
      chi-squared test. RESULTS: Of 929 patients enrolled, 64.8% (516/796) of evaluable
      patients completed 1 year of treatment. There was no statistically significant
      difference in the proportion of treatment completers between the olanzapine
      cohort (67.4%, 256/380) and the other SGA cohort (62.5%, 260/416). Treatment
      completion rates were risperidone 62.0% (127/205), quetiapine 63.7% (123/193) and
      clozapine 55.6% (10/18). Antipsychotic polypharmacy was common. Patients treated
      with olanzapine or risperidone had significantly higher increases in BMI than
      quetiapine-treated patients. There were no major differences between olanzapine
      monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal
      symptoms from baseline to endpoint. CONCLUSIONS: Olanzapine and other SGAs
      exhibited similar rates of 1-year treatment completion. Further study of
      medication combinations is needed, given their perceived clinical value, and the
      high frequency of antipsychotic polypharmacy in clinical practice. LIMITATIONS:
      As most patients received several psychotropics and power was reduced in
      monotherapy analyses, comparisons between cohorts must be interpreted cautiously.
      Comparisons between individual antipsychotics were post hoc and not powered a
      priori. Accuracy and completeness of adverse event information for drugs other
      than olanzapine is limited.

PMID- 19601708
TI  - Unpredictability of glaucoma progression.
AB  - BACKGROUND: Glaucoma is a chronic, progressive ocular neuropathy that leads to
      the loss of retinal ganglion cells and varying degrees of visual impairment or
      blindness. MANAGEMENT: There are three major factors to consider in the
      management of patients with glaucoma. First, extensive damage to retinal ganglion
      cells often can occur before the appearance of any functional deficits is
      detected by perimetry. Second, the rate of glaucoma progression varies
      considerably among different patients and even for the same patient at different
      times. Third, the lack of correspondence between structural and functional change
      may reflect the limitations of current assays in measuring each. Given the
      variability of disease progression, early detection and continued vigilance of
      both structure and function in the form of regular patient monitoring are
      essential. CONCLUSION: This review presents six case histories that demonstrate
      the differing rates of progression that may be observed in the clinic and the
      importance of early detection and treatment in controlling the disease. In
      addition, major lessons from randomised clinical trials are summarised, including
      the likelihood of progression from diagnosed ocular hypertension to the
      development of glaucoma, the risks of progression of established glaucoma and the
      effectiveness of therapy.

PMID- 19601709
TI  - Randomized, double-blind, placebo-controlled trial of every-3-week darbepoetin
      alfa 300 micrograms for treatment of chemotherapy-induced anemia.
AB  - OBJECTIVE: Darbepoetin alfa is effective in treating chemotherapy-induced anemia
      (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could
      simplify treatment through synchronization with common Q3W chemotherapy regimens.
      We report results from a multicenter, randomized, double-blind, placebo
      controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W
      darbepoetin alfa in patients with a wide variety of tumor types who experienced
      CIA. RESEARCH DESIGN AND METHODS: Patients aged > or = 18 years with anemia
      (hemoglobin <11 g/dL) being treated for nonmyeloid malignancy were randomized 1:1
      to receive darbepoetin alfa 300 microg (n = 193) or placebo (n = 193)
      subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be
      adjusted per prespecified rules. MAIN OUTCOME MEASURES: The primary endpoint was
      the proportion of patients who received > or =1 red blood cell (RBC) transfusion
      between week 5 and the end of the treatment period (EOTP). The study also
      analyzed the proportions of patients achieving a hemoglobin concentration > or
      =11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL, and the
      change in hemoglobin concentration over time. RESULTS: The proportion of patients
      requiring RBC transfusions between week 5 and EOTP was significantly lower in the
      darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of
      patients, a 16.3% difference, p < 0.001). There were no differences between the
      two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic
      adverse events were uncommon and were not associated with increases in hemoglobin
      levels. Study limitations suggest caution in the interpretation of these results:
      transfusions, the primary endpoint, were recommended but not required if
      hemoglobin concentrations were < or =8.0 g/dL, and protocol deviations (primarily
      dosing errors) occurred in approximately one-half of the patients in both
      treatment groups. CONCLUSIONS: In this study, fixed-dose Q3W darbepoetin alfa
      appeared to be well-tolerated and effective for the treatment of CIA. TRIAL
      REGISTRATION: Study 20030232; ClinicalTrials.Gov Identifier: NCT00110955.

PMID- 19601711
TI  - Estimating the economic impact of a half-day reduction in length of hospital stay
      among patients with community-acquired pneumonia in the US.
AB  - BACKGROUND: A recent study suggested that levofloxacin significantly reduces the
      hospital length of stay (LOS), by 0.5 days (p = 0.02), relative to moxifloxacin
      in patients with community-acquired pneumonia (CAP). The current analysis
      evaluated the potential economic impact of this half-day reduction in LOS.
      METHODS: A cost model was developed to estimate the impact of a half-day
      reduction in LOS for CAP hospitalizations in the US. CAP incidence,
      hospitalization rate, and costs were obtained from published studies in PubMed
      and from publicly available government sources. The average daily cost of
      hospitalization was estimated for fixed costs, which comprise 59% of total
      inpatient costs. Costs from prior years were inflated to 2007 US dollars using
      the consumer price index. A range of cost savings, calculated using inpatient CAP
      costs from several studies, was extrapolated to the US CAP population. RESULTS:
      Using the Centers for Disease Control National Hospital Discharge estimate of 5.3
      days LOS for CAP, and an average cost (2007 $US) of $13,009 per CAP
      hospitalization, a daily fixed cost of $1448 was estimated. The resultant half
      day reduction in costs associated with LOS was $724/hospitalization (range $457
      to $846/hospitalization). When fixed and variable costs were considered, the
      estimated savings were $1227.27/episode. The incidence of CAP was estimated to be
      1.9% (5.7 million cases/year based on current population census), and the
      estimated rate of CAP hospitalization was 19.6% (1.1 million annual
      hospitalizations). At $13,009/CAP-related hospitalization, total fixed inpatient
      costs of $8.6 billion annually were projected. The half-day reduction in LOS
      would therefore generate potential annual savings of approximately $813 million
      (range $513 million to $950 million). When total costs (fixed plus variable) were
      estimated, the mean savings for a half-day reduction would be approximately
      $1227/episode (range of $775 to $1434) or $1.37 billion annually in the US CAP
      population (range of $871 million to $1.6 billion). Limitations include the use
      of a single study for the estimation of fixed costs but a diversity of sources
      used for estimates of other variables, and lack of data with respect to the
      effects on costs of diagnostic-related groups, discounted contracts, and
      capitated payments. CONCLUSIONS: A relatively small decrease in LOS in CAP can
      have a substantial cost impact, with estimated savings of $457 to $846 per
      episode or $500-$900 million annually. Additional evaluation is warranted for
      interpreting these cost-savings in the context of current antibiotic prescribing
      patterns.

PMID- 19601710
TI  - Potential concerns about generic substitution: bioequivalence versus therapeutic
      equivalence of different amlodipine salt forms.
AB  - BACKGROUND AND SCOPE: Whether generic drug products are truly therapeutically
      identical and interchangeable with their innovator counterparts is still a matter
      of debate. This review discusses the controversies related to the criteria for
      bioequivalence and therapeutic equivalence. These concerns are illustrated by
      using the calcium antagonist amlodipine besylate (innovator drug) versus
      amlodipine maleate (generic), indicated for the treatment of hypertension and
      angina pectoris, as an example. METHODS: English-language publications were
      searched in Medline and EMBASE to retrieve all references on amlodipine maleate
      and literature related to the regulatory guidelines for bioequivalence and
      therapeutic equivalence to August 2008. Websites from the European and US
      regulatory authorities were also consulted. FINDINGS: According to regulatory
      definitions, generic drug products need to be identical to their reference with
      respect to the active substance, the route of administration as well as quality
      standards. In contrast to innovator drugs, which have to demonstrate their
      clinical efficacy and safety, generics are considered therapeutically equivalent
      based on simple bioequivalence testing. In addition, bioequivalence is
      established with a disputable study method (single dose in a small group of
      healthy subjects) and statistics (broad acceptance intervals). Consequently, a
      potential negative impact of alternative salt forms or excipients on the clinical
      profile of a drug may remain undetected. To exemplify this, although amlodipine
      maleate is known to contain (degradation) impurities with (potential) biological
      activity, it is found per definition bioequivalent to its innovator drug,
      amlodipine besylate. However, only two clinical studies compared the
      antihypertensive and safety profiles of both drugs up to 3 months, without CV
      event endpoints. CONCLUSIONS: The validity of the current criteria for
      interchangeability of generic and innovator drugs remains controversial and may
      compromise the response and/or safety of patients. In the case of amlodipine,
      thorough long-term clinical investigations of commercial amlodipine maleate salt
      preparations including hard endpoints may be needed to justify their use.

PMID- 19601712
TI  - Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory
      factor (MIF): regulatory role of TRX on MIF internalization and signaling.
AB  - Thioredoxin-1 (TRX) is a small (14 kDa) multifunctional protein with the redox
      active site Cys-Gly-Pro-Cys. Macrophage migration inhibitory factor (MIF) is a 12
      kDa cytokine belonging to the TRX family. Historically, when we purified TRX from
      the supernatant of ATL-2 cells, a 12 kDa protein was identified along with TRX,
      which was later proved to be MIF. Here, we show that TRX and MIF form a complex
      in the cell and the culture supernatant of ATL-2 cells. Using a BIAcore assay, we
      confirmed that TRX has a specific affinity with MIF. We also found that
      extracellular MIF was more effectively internalized into the ATL-2 cells
      expressing TRX on the cell surface, than the Jurkat T cells which do not express
      surface TRX. Moreover, anti-TRX antibody blocked the MIF internalization,
      suggesting that the cell surface TRX is involved in MIF internalization into the
      cells. Furthermore, anti-TRX antibody inhibited MIF-mediated enhancement of TNF
      alpha production from macrophage RAW264.7 cells. These results suggest that the
      cell surface TRX serves as one of the MIF binding molecules or MIF receptor
      component and inhibits MIF-mediated inflammatory signals.

PMID- 19601713
TI  - Potential existence of stem cells with multiple differentiation abilities to
      three different germ lineages in mouse neurospheres.
AB  - Neural stem cells (NSCs) are tissue-specific stem cells with self-renewal
      potential in brain, and are committed cells of the central nervous system.
      Recently, some reports have suggested the possibility of the NSCs to
      differentiate into non-CNS mesodermal derivatives, such as blood cells and
      skeletal muscle cells. Here we isolated NSCs as neurospheres from a neonatal
      mouse brain using serum replacement medium, and demonstrated that the stem cell
      population expressing pluripotent-related genes such as Oct-4, Sox-2, and Nanog
      possess multiple differentiation potentials to ectodermal, mesodermal, and
      endodermal lineages, that is, some neural cells, beating cardiomyocytes,
      adipocytes, and insulin-producing cells. The results of the present study partly
      provide further evidence for multiple differentiation properties of NSCs and
      suggest common characteristics between NSCs and other pluripotent stem cells.

PMID- 19601715
TI  - Aim of this special issue.

PMID- 19601716
TI  - Importance of knowledge on drug metabolism for the safe use of drugs in humans.

PMID- 19601717
TI  - Therapeutic management of allergic diseases.
AB  - Allergic diseases are characterized by the activation of inflammatory cells and
      by a massive release of mediators. The aim of this chapter was to describe
      succinctly the modes of action, indications, and side effects of the major
      antiallergic and antiasthmatic drugs. When considering the ideal pharmacokinetic
      characteristics of a drug, a poorly metabolized drug may confer a lower
      variability in plasma concentrations and metabolism-based drug interactions,
      although poorly metabolized drugs may be prone to transporter-based disposition
      and interactions. The ideal pharmacological properties of a drug include high
      binding affinity, high selectivity, and appropriate association and dissociation
      rates. Finally, from a patient perspective, the frequency and route of
      administration are important considerations for ease of use.

PMID- 19601718
TI  - Drug metabolism and pharmacokinetics.
AB  - In this article, aspects of absorption, distribution, metabolism, and excretion
      have been described bearing in mind the pathogenesis of allergic diseases and
      their possible therapeutic opportunities. The importance of the routes of
      administration of the different therapeutic groups has been emphasized. The
      classical aspects of drug metabolism and disposition related to oral
      administration have been reviewed, but special emphasis has been given to
      intranasal, cutaneous, transdermal, and ocular administration as well as to the
      absorption and the subsequent bioavailability of drugs. Drug-metabolizing enzymes
      and transporters present in extrahepatic tissues, such as nasal mucosa and the
      respiratory tract, have been particularly discussed. As marketed antiallergic
      drugs include both racemates and enantiomers, aspects of stereoselective
      absorption, distribution, metabolism, and excretion have been discussed. Finally,
      a new and promising methodology, microdosing, has been presented, although it has
      not yet been applied to drugs used in the treatment of allergic diseases.

PMID- 19601719
TI  - Physiologically based pharmacokinetics (PBPK).
AB  - Allometric scaling is widely used to predict human pharmacokinetic parameters
      from preclinical species, and many different approaches have been proposed over
      the years to improve its predictive performance. Nevertheless, prediction errors
      are commonly observed in the practical application of simple allometry, for
      example, in cases where the hepatic metabolic clearance is mainly determined by
      enzyme activities, which do not scale allometrically across species. Therefore,
      if good correlation was noted for some drugs, poor correlation was observed for
      others, highlighting the need for other conceptual approaches. Physiologically
      based pharmacokinetic (PBPK) models are now a well-established approach to
      conduct extrapolations across species and to generate simulations of
      pharmacokinetic profiles under various physiological conditions. While
      conventional pharmacokinetic models are defined by drug-related data themselves,
      PBPK models have richer information content and integrate information from
      various sources, including drug-dependent, physiological, and biological
      parameters as they vary in between species, subjects, or with age and disease
      state. Therefore, the biological and mechanistic bases of PBPK models allow the
      extrapolation of the kinetic behavior of drugs with regard to dose, route, and
      species. In addition, by providing a link between tissue concentrations and
      toxicological or pharmacological effects, PBPK modeling represents a framework
      for mechanistic pharmacokinetic-pharmacodynamic models.

PMID- 19601720
TI  - Gender and interindividual variability in pharmacokinetics.
AB  - Like any other drugs, antiallergic medications can be associated with large inter
      and intraindividual variability in their disposition. The best-documented
      examples belong to the H1 antihistamines. Variable drugs are more likely to show
      unpredictable therapeutic response with both increased risks of side effects and
      subtherapeutic dosing in individual subjects. This article will review the main
      factors contributing to intervariability in pharmacokinetics with a special
      emphasis on gender differences, genetic polymorphism, and food habits.

PMID- 19601721
TI  - Pharmacokinetics in special populations.
AB  - Pharmacokinetics are typically dependent on a variety of physiological variables
      (e.g., age, ethnicity, or pregnancy) or pathological conditions (e.g., renal and
      hepatic insufficiency, cardiac dysfunction, obesity, etc.). The influence of some
      of these conditions has not always been thoroughly assessed in the clinical
      studies of antiallergic drugs. However, the knowledge of the physiological
      grounds of the pharmacokinetics can provide some insight for predicting the
      potential alterations and guiding the initial prescription strategies. It is
      important to recognize that both pharmacokinetic and pharmacodynamic differences
      between populations should be considered. The available information on drugs used
      for the therapy of allergic diseases is reviewed in this chapter.

PMID- 19601722
TI  - From pharmacokinetics to therapeutics.
AB  - Whilst pharmacokinetics describe the relationship between dose levels and
      concentration-time profiles of a drug in the body and pharmacodynamics describe
      the concentration-response relationships, pharmacokinectics-pharmacodynamics(PK
      PD) models link these two items providing a framework for modelling the time
      course of drug response. In this chapter, PK-PD models, describing the
      therapeutic effects of drugs used for the therapy of allergic diseases have been
      reviewed. Emphasis was given also to the description of the receptor occupancy,
      which is tightly related to the downstream clinical response. PK - PD models
      describing unwanted effects were also commented. An integrated use of these
      models allows choosing appropriate dosing regimens and providing an objective
      evaluation of the benefit/risk balance.

PMID- 19601723
TI  - Population pharmacokinetic and pharmacodynamic analysis in allergic diseases.
AB  - In this chapter, we introduce the concepts and methodologies of population
      analysis as applied to analyzing pharmacokinetic and pharmacodynamic data. One of
      the key determining characteristics of the population approach is that through
      it, one seeks not only to characterize deterministic trends in the data, but also
      to identify and estimate the magnitudes of the important sources of variability
      within the data. The first section of this chapter provides an introduction to
      the primary concepts of, and motivation for, population modeling by way of a
      hypothetical case study. Then, the various methodologies that have been employed
      throughout the history of population analysis are described in further detail. Of
      these, the most commonly employed today is nonlinear mixed-effects (NLME)
      modeling. Finally, notable examples of the application of population PK and PK/PD
      modeling to treatments for allergies and asthma are discussed. Population PK
      models have frequently been used to extrapolate exposures to special populations,
      such as pediatrics, as well as to optimize treatment regimens and trial designs
      for these populations. Population PK/PD models have most frequently been applied
      to analyzing and interpreting data from wheal and flare trials, but are also
      becoming increasingly important in the analysis of PD data from monoclonal
      antibodies.

PMID- 19601725
TI  - General conclusions.

PMID- 19601724
TI  - Drug interactions.
AB  - Drugs for allergy are often taken in combination with other drugs, either to
      treat allergy or other conditions. In common with many pharmaceuticals, most such
      drugs are subject to metabolism by P450 enzymes and to transmembrane transport.
      This gives rise to considerable potential for drug-drug interactions, to which
      must be added consideration of drug-diet interactions. The potential for
      metabolism-based drug interactions is increasingly being taken into account
      during drug development, using a variety of in silico and in vitro approaches.
      Prediction of transporter-based interactions is not as advanced. The clinical
      importance of a drug interaction will depend upon a number of factors, and it is
      important to address concerns quantitatively, taking into account the therapeutic
      index of the compound.

PMID- 19601726
TI  - Chemical structures of the most cited drugs discussed in this special issue.

PMID- 19601727
TI  - Combined hepatitis A and B vaccine: providing a bright future for preventing
      hepatitis.
AB  - The first combined hepatitis A and B vaccine has been available in the United
      States since 2001. The vaccine provides protection against viral hepatitis with
      rapid seroprotection and lasting immunogenicity. This review outlines the
      product's components, clinical efficacy and opportunities for use in special
      circumstances. The vaccine has a good safety profile and has good tolerability.
      The combined hepatitis A and B vaccine is a well studied vaccine that provides
      rapid seroconversion with a good safety profile.

PMID- 19601730
TI  - Foodborne illness levels off in past several years. CDC report states overall
      progress stopped in 2004.

PMID- 19601728
TI  - Development of an allergen extract for sublingual immunotherapy--evaluation of
      Staloral.
AB  - BACKGROUND: Specific immunotherapy (IT) is an effective treatment for rhinitis
      and asthma caused by aeroallergens sensitization. Sublingual IT (SLIT) was
      introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT)
      and developed to represent an actual treatment option. It is now generally
      accepted that allergen doses much higher than those administered by SCIT must be
      used to achieve clinical efficacy on allergic symptoms. OBJECTIVE: To evaluate
      the characteristics of Staloral, an allergen extract produced by Stallergenes
      (Antony, France) in terms of practical administration, efficacy, safety and
      mechanism of action. METHODS: Data were obtained from 20 double-blind, placebo
      controlled studies using Staloral in patients sensitized to pollens and house
      dust mites, and also from open studies concerning practical administration and
      the mechanism of action. RESULTS/CONCLUSION: Efficacy and safety of Staloral, as
      demonstrated by the revision of the studies, which used doses up to 1125 times
      those administered with SCIT, are very satisfactory and confer to this allergen
      extract optimal characteristics for treating patients with seasonal allergies due
      to pollens or with perennial symptoms induced by dust mites. The main mechanism
      of action is the interaction with dendritic cells of the oral mucosa and the
      subsequent tolerance induced in T cells.

PMID- 19601731
TI  - Thoughts on mandatory spay/neuter programs.

PMID- 19601732
TI  - What is your diagnosis? Osteochondritis dissecans.

PMID- 19601733
TI  - Pathology in practice. Histoplasma capsulatum infections.

PMID- 19601734
TI  - Characterization of animals with microchips entering animal shelters.
AB  - OBJECTIVE: To characterize animals with microchips entering animal shelters and
      the process used to find owners. DESIGN: Cross-sectional study. ANIMALS: 7,704
      microchipped animals entering 53 animal shelters between August 2007 and March
      2008. PROCEDURES: Data for animals with microchips were recorded by participating
      animal shelters and reported monthly. RESULTS: Of 7,704 animals, strays accounted
      for slightly more than half (4,083 [53.0%]), with the remainder classified as
      owner-relinquished animals (3,225 [41.9%]) and other (396 [5.1%]). Of 3,425 stray
      animals for which animal shelters reported that the owner was found, a higher
      percentage of dog owners (2,191/2,956 [74.1%]) than cat owners (298/469 [63.5%])
      was found. For 876 animals for which the owners could not be found, the main
      reasons were incorrect or disconnected telephone number (310 [35.4%]), owner did
      not return telephone calls or respond to a letter (213 [24.3%]), and animal was
      registered to another group (151 [17.2%]). Of 1,943 animals for which animal
      shelters contacted a microchip registry, 1,129 (58.1%) were registered in the
      database. Purebred neutered dogs whose owner information was in the shelter
      database registry or microchip registry had a higher likelihood that the owners
      would be found. CONCLUSIONS AND CLINICAL RELEVANCE: The high rate for return of
      microchipped dogs and cats to their owners supported microchipping as a valuable
      permanent pet identification modality; however, issues related to registration
      undermined its overall potential. Bundling of microchip implantation and
      registration, point-of-implantation data registration, use of annual compliance
      and update reminders, and providing access to all registries are potential
      solutions.

PMID- 19601736
TI  - Use of a selective serotonin reuptake inhibitor for treatment of episodes of
      hypertonia and kyphosis in a young adult Scottish Terrier.
AB  - CASE DESCRIPTION: A 2.5-year-old 12.4-kg (27.3-lb) castrated male Scottish
      Terrier was evaluated because of episodes of hypertonia and kyphosis for which a
      presumptive diagnosis of so-called Scottie cramp had been made when the dog was a
      puppy. CLINICAL FINDINGS: Findings of general physical, orthopedic, and
      neurologic examinations were within reference limits. Pelvic limb hypertonicity
      and kyphosis without signs of pain were induced with minimal exercise; ambulation
      returned to normal after a period of rest. TREATMENT AND OUTCOME: Fluoxetine, a
      selective serotonin reuptake inhibitor, was administered orally at a dosage of
      1.2 mg/kg (0.55 mg/lb) once daily for 1 month. After this period of treatment,
      clinical signs of the disease were greatly reduced; the dosage of fluoxetine was
      changed to 0.8 mg/kg (0.36 mg/lb) twice daily, and response to treatment
      continued. CLINICAL RELEVANCE: Administration of benzodiazepines, vitamin E, or
      phenothiazines has been recommended for treatment of episodes of hypertonicity,
      but often does not result in control of clinical signs. It has been suggested
      that the pathogenesis of this disease is related to deficiencies in concentration
      or function of serotonin in the CNS; thus, a logical choice for treatment is
      administration of a serotonin reuptake inhibitor. In the dog of this report,
      fluoxetine resulted in good control of clinical signs. The use of an effective
      medication (other than a controlled substance) that is administered once or twice
      daily, has minimal adverse effects on the patient's mental status, and is
      inexpensive may lead to better owner compliance and an improved quality of life
      for affected dogs.

PMID- 19601738
TI  - Severe polymyositis and neuritis in a cat.
AB  - CASE DESCRIPTION: A 4-year-old domestic shorthair cat was evaluated for a 1-week
      history of shifting limb lameness that progressed to tetraparesis. CLINICAL
      FINDINGS: Physical examination revealed generalized muscle atrophy and signs of
      discomfort when the muscles of the appendicular skeleton were palpated.
      Neurologic examination revealed diminished myotatic and withdrawal reflexes in
      all 4 limbs. Results of a CBC indicated mild neutrophilia, and serum biochemical
      analysis revealed mild hyperalbuminemia and high creatine kinase activity. The
      cat was anesthetized, and an electromyogram (EMG), CSF sample, and nerve and
      muscle biopsy specimens were obtained. The EMG revealed positive sharp waves and
      fibrillation potentials, CSF analysis revealed albuminocytologic dissociation,
      and histologic examination of muscle and nerve specimens revealed severe myositis
      and neuritis. Immune-mediated polymyositis and neuritis were suspected. TREATMENT
      AND OUTCOME: With physical therapy and long-term corticosteroid drug treatment,
      the cat recovered complete motor nerve function. CLINICAL RELEVANCE: The severity
      and rapid progression of clinical signs, combined with the EMG abnormalities and
      histologic findings, could have led to inappropriate euthanasia for this cat.
      Veterinarians should be aware that immune-mediated polymyositis and neuritis in
      cats can have an excellent prognosis with appropriate, long-term treatment.

PMID- 19601739
TI  - Factors predictive of abnormal results for computed tomography of the head in
      horses affected by neurologic disorders: 57 cases (2001-2007).
AB  - OBJECTIVE: To determine neurologic indications associated with abnormal results
      for computed tomography (CT) imaging of the head of horses affected by neurologic
      disorders. DESIGN: Retrospective case series. ANIMALS: 57 horses. PROCEDURES:
      Signalment, history, clinical abnormalities, and clinicopathologic findings were
      obtained from medical records of horses examined because of neurologic disorders,
      and precontrast and postcontrast CT images of the head were reviewed. Data were
      analyzed by use of univariate and multivariate logistic regression. RESULTS: For
      a horse with abnormal mentation, odds of having abnormal results for CT imaging
      of the head was 30 times (95% confidence interval [CI], 2.36 to 374.63) the odds
      for a similar horse without abnormal mentation. For a horse with cranial nerve
      deficits, odds of having abnormal results for CT imaging of the head was 11 times
      (95% CI, 1.00 to 127.96) the odds for a similar horse without cranial nerve
      deficits. For a horse with seizure-like activity, odds of having abnormal results
      for CT imaging of the head was 0.05 times (95% CI, 0 to 0.90) the odds for a
      similar horse without seizures. CONCLUSIONS AND CLINICAL RELEVANCE: These results
      suggested that alterations in consciousness and cranial nerve deficits were
      strong predictors of abnormal CT findings for the head of affected horses. Thus,
      CT can be a useful complementary diagnostic test in horses with these neurologic
      deficits. In contrast, alternative diagnostic tests (eg, electroencephalography
      and magnetic resonance imaging) should be considered in horses with seizure-like
      activity that do not have head trauma or cranial nerve deficits.

PMID- 19601740
TI  - Pneumocephalus secondary to removal of an osteoma from the paranasal sinuses of a
      horse.
AB  - CASE DESCRIPTION: A 2-year-old Quarter Horse was evaluated because of a
      progressive left-sided facial deformity and unilateral nasal and ocular
      discharge. CLINICAL FINDINGS: Physical examination revealed convexity of the left
      frontonasal region, left-sided nasal and ocular discharge, and decreased air flow
      through the left nares. Radiography and computed tomography revealed an
      extensively mineralized mass occupying most of the left paranasal sinuses.
      TREATMENT AND OUTCOME: The mass was surgically debulked, but complete removal was
      precluded because the mass was tightly adhered to the frontal and maxillary
      bones. Results of histologic examination of the mass were consistent with a
      diagnosis of osteoma. The horse developed transient pyrexia and colic following
      surgery, and postoperative radiography revealed gas opacities in the lateral
      ventricles of the brain, consistent with iatrogenic pneumocephalus. However, the
      horse did not develop any neurologic signs and was performing normally 2 years
      after surgery. CLINICAL RELEVANCE: Findings reinforce concerns that paranasal
      sinus surgery in horses can be associated with intracranial complications such as
      pneumocephalus. In horses with a mass involving the paranasal sinuses, computed
      tomography may be helpful in determining the boundaries of the mass and
      formulating a surgical treatment plan.

PMID- 19601741
TI  - Treatment of acute epistaxis secondary to guttural pouch mycosis with
      transarterial nitinol vascular occlusion plugs in three equids.
AB  - CASE DESCRIPTION: 2 horses and 1 pony were evaluated for right-sided (1 horse and
      the pony) and left-sided (1 horse) acute epistaxis of 1 day's to 1 month's
      duration. CLINICAL FINDINGS: Endoscopic examination of the 3 equids revealed that
      the hemorrhage originated from the right maxillary artery in 2 equids and from
      the left internal carotid artery in the third. Mycosis of the auditory tube
      diverticulum (guttural pouch) was detected in all 3 equids. TREATMENT AND
      OUTCOME: All 3 equids underwent surgery, and transarterial nitinol intravascular
      plugs were placed to occlude affected blood vessels. All equids survived for a
      long period (ie, a minimum of 1 to 2 years) and returned to their previous use.
      All had complete regression of clinical signs of guttural pouch mycosis without
      additional medical treatment. CLINICAL RELEVANCE: The use of transarterial
      nitinol intravascular plugs appeared to be an effective alternative to other
      techniques for the treatment of epistaxis secondary to guttural pouch mycosis,
      including transarterial occlusion devices such as embolization coils.

PMID- 19601742
TI  - Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload.
AB  - CASE DESCRIPTION: 3 adult (24- to 43-year-old) Atlantic bottlenose dolphins
      (Tursiops truncatus) with chronic episodic malaise and inappetence associated
      with high serum aminotransferase (alanine aminotransferase and aspartate
      aminotransferase) activities, high serum iron concentration, and serum
      transferrin saturation > 80% were evaluated. CLINICAL FINDINGS: Results of
      histologic examination of liver biopsy specimens revealed hemosiderosis in all 3
      dolphins. Except for chronic lymphocytosis in 1 dolphin, results of extensive
      diagnostic testing revealed no other abnormalities. For each dolphin, a diagnosis
      of iron overload of unknown origin was made. TREATMENT AND OUTCOME: Phlebotomy
      treatment was implemented to reduce body stores of iron. Each phlebotomy
      procedure removed 7% to 17% (1 to 3 L) of estimated blood volume. Treatment
      consisted of an induction phase of weekly phlebotomy procedures for 22 to 30
      weeks, which was complete when serum iron concentration and aminotransferase
      activities were within reference ranges and serum transferrin saturation was < or
      = 20% or Hct was < or = 30%. Total amount of iron removed from each dolphin was
      53 to 111 mg/kg (24.1 to 50.5 mg/lb) of body weight. One dolphin required
      maintenance procedures at 8- to 12-week intervals when high serum iron
      concentration was detected. CLINICAL RELEVANCE: Although the cause of the iron
      overload and high serum aminotransferase activities remained unknown, phlebotomy
      treatment successfully resolved the clinicopathologic abnormalities, supporting a
      role of iron overload in the hepatopathy of the 3 dolphins.

PMID- 19601743
TI  - Protein targets in the treatment of cancers.

PMID- 19601744
TI  - Estrone sulfatase and its inhibitors.
AB  - A high proportion (approximately 40%) of breast cancers are hormone-dependent and
      it is the female hormone estradiol (E2) that is believed to play a key role in
      the initiation, promotion and progression of this disease. In the fight against
      this disease, compounds which are potent inhibitors of the cytochrome P-450
      enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the
      C18 estrogens) have been the major target. However, the administration of AR
      inhibitors alone does not prevent the localised biosynthesis of estrone (E1) (and
      therefore the subsequent synthesis of E2) within breast tumour cells via
      alternative non-AR routes. This has therefore been the major impetus for the
      development of steroid sulfatase (E1STS) inhibitors. The E1STS enzyme regulates
      the formation of E1 from estrone sulfate (E1S), a steroid conjugate present in
      high concentrations in tissue and blood in women with breast cancer. The STS
      enzyme has also been shown to catalyse the formation of dehydroepiandrosterone
      (DHEA) from DHEA-sulfate (DHEAS). This is important since DHEA can be converted
      to 5-androstene-3beta,17beta-diol, which has been shown to possess weak
      estrogenic properties, however, due to the high concentration of this steroid, it
      is able to stimulate the growth of breast cancer cells in vitro and in vivo.
      Considerable progress has been made in recent years in the development of a
      number of potent E1STS inhibitors, as such both steroidal and non-steroidal
      compounds have been considered and a number of highly potent inhibitors have been
      produced and evaluated against what is now considered a crucial enzyme in the
      fight against hormone-dependent breast cancer. The review therefore summarises
      the work that has been undertaken todate.

PMID- 19601745
TI  - 17alpha-hydroxylase/17,20-lyase (p450(17alpha)) inhibitors in the treatment of
      prostate cancer: a review.
AB  - Prostate cancer is an age-related disease and a major cause of death in Western
      countries. A large proportion of prostate cancers have been found to be dependent
      on androgens for growth and various therapeutic approaches have aimed at either
      decreasing androgen levels or blocking their action. One method of decreasing
      androgen levels is through inhibition of enzymes involved in the biosynthetic
      pathway, for example, the P450 enzyme complex 17alpha-hydroxylase/C17,20-lyase
      (P450(17alpha)), which catalyses the conversion of pregnenolone and progesterone
      into the androgen precursors dehydroepiandrosterone and androstenedione
      respectively. A number of researchers have targeted this enzyme and have produced
      potent steroidal and non-steroidal inhibitors. This review looks at the various
      inhibitors that have been developed, focussing mainly on more recent inhibitors
      reported over the last ten years. Some mention is also given to structural
      requirements suggested to be important for potent activity.

PMID- 19601746
TI  - Aromatase: the enzyme and its inhibition.
AB  - The genetic control, mechanism of action and inhibition of aromatase for
      potential therapeutic benefits in the arena of hormone dependent illness
      continues to be of considerable interest. The work presented here concentrates on
      recent advances in the mechanistic aspects of the aromatase enzyme and the nature
      of the chemical entities that lead to its inhibition.

PMID- 19601747
TI  - Advances in development of inhibitors of 17beta hydroxysteroid dehydrogenases.
AB  - The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the
      regulation of estrogens and androgens by catalyzing the reduction of 17
      ketosteroids or the oxidation of 17beta hydroxysteroids. The enzyme activities
      associated with the different 17beta-HSD isoforms are widespread in human
      tissues, not only in classic steroidogenic tissues but also in a large series of
      peripheral intracrine tissues. Being involved at the end of steroidogenesis, the
      numerous members of 17beta-HSD family constitute interesting therapeutic targets
      for controlling the concentration of estrogens and androgens. Thus, inhibitors of
      reductive 17beta-HSD isoforms are attractive to block the formation of
      hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian,
      and endometrium cancers) and androgeno-sensitive pathologies (prostate cancer,
      benign prostatic hyperplasia, acne, and hirsutism). The inhibitors could be used
      to block the degradation of estradiol, an attractive strategy for treating
      osteoporosis and Alzheimer's disease. In addition to their classical use as anti
      cancer agents and therapeutic agents, inhibitors of 17beta-HSDs are also useful
      tools to elucidate the role of these enzymes in particular biological systems.
      The present review article gives a description of novel inhibitors of 17beta-HSDs
      that were published in 2003-2006.

PMID- 19601748
TI  - Histone deacetylase inhibitors: design, structure-activity relationships and
      therapeutic implications for cancer.
AB  - Histone deacetylases (HDACs) remove acetyl groups from the tails of lysine
      residues of histone protein in nuclear chromatin and also from acetylated sites
      in non-histone proteins. HDACs and histone acetyltransferases (HATs) are major
      influences on the level of cellular protein acetylation, and an imbalance in
      acetylation levels, particularly under-acetylated (hypoacetylated) histone
      protein has been associated with precancerous or malignant states. Consequently,
      small molecule inhibitors of HDACs have been synthesised and some now form a
      newly emerging class of anti-cancer agents that can regulate transcription and
      inhibit proliferation of cancer cells by inducing cell cycle arrest,
      differentiation and/or apoptosis, among other major biological phenomena. The
      different mechanism(s) of action of HDAC inhibitors compared to conventional anti
      neoplastic agents provides a possibility that HDAC inhibitors may be effective
      for refractory cancers. Accordingly, a number of programs for the development of
      HDAC inhibitors as anti-cancer drugs have been initiated. This review highlights
      recent developments in the design, synthesis and biological properties of HDAC
      inhibitors in the context of potential cancer therapy.

PMID- 19601749
TI  - Inhibition of carbonic anhydrase IX: a new strategy against cancer.
AB  - Of the thirteen active carbonic anhydrase (CA) isozymes, the transmembrane
      isoform CA IX has been shown to be linked with carcinogenesis. CA IX presents an
      ectopic expression in a multitude of carcinomas derived from cervix, uteri,
      kidney, lung, oesophagus, breast, colon, etc., contrasting with its restricted
      expression in normal tissues, namely in the epithelia of the gastrointestinal
      tract. It has been demonstrated that this membrane-bound CA is strongly
      overexpressed in hypoxic tumors, participating in tumor cell environment acidosis
      and contributing to malignant progression and poor treatment outcome. Targeting
      CA IX could thus be an important means of controlling cancer disease. Modulation
      of extracellular tumor pH via inhibition of CA IX activity represents a promising
      approach to novel anticancer therapies. Much attention has recently been paid to
      the CA IX inhibitors drug design, and efforts have been made to obtain isozyme IX
      inhibitors, with putative applications as antitumor drugs/diagnostic agents. This
      review will focus on the different CA IX inhibitors described in the literature
      which could represent excellent potential as candidate therapeutic agents in
      cancer chemotherapy.

PMID- 19601751
TI  - Combinatorial and high throughput screening of cell response to biomaterials
      (part 1).

PMID- 19601750
TI  - The epidermal growth factor receptor as a therapeutic target in glioblastoma
      multiforme and other malignant neoplasms.
AB  - The epidermal growth factor receptor (EGFR) is dysregulated in various tumour
      types such as glioblastoma multiforme (GBM), breast cancer, ovarian carcinoma,
      non-small cell lung cancer and other cancers. As the intracellular tyrosine
      kinase of the EGFR activates signalling cascades leading to cell proliferation,
      angiogenesis and inhibition of apoptosis, the EGFR represents an attractive
      target in cancer therapy. In GBM which is the most common primary central nervous
      system tumour in adults, the EGFR is overexpressed in about 40 to 50% of cases,
      and almost half of these co-express the mutant receptor subtype EGFRvIII. This
      EGFR variant is constitutively activated, and thereby may contribute to the
      aggressive and refractory course of GBM which is associated with a median
      survival of only 40 to 60 weeks from diagnosis. Various trials are ongoing
      focusing on EGFR and EGFRvIII as new therapeutic targets in GBM. Anti-EGFR
      monoclonal antibodies (MAbs), e.g. cetuximab, and tyrosine kinase inhibitors
      (TKIs), e.g. erlotinib and gefitinib, are the most advanced in clinical
      development. Several trials are investigating MAbs or TKIs in combination with
      other agents such as inhibitors of the mammalian target of rapamycin. Other still
      preliminary approaches targeting the EGFR are small interfering RNA, antisense
      RNA and ribozymes, which lead to degradation of EGFR mRNA. Further studies are
      needed to define their clinical potential, to identify biological predictors of
      response and thus to characterize subgroups of patients who will benefit from
      treatment with these new agents.

PMID- 19601752
TI  - Cell interactions with biomaterials gradients and arrays.
AB  - Gradients and arrays have become very useful to the fields of tissue engineering
      and biomaterials. Both gradients and arrays make efficient platforms for
      screening cell response to biomaterials. Graded biomaterials also have functional
      applications and make useful substrates for fundamental studies of cell phenomena
      such as migration. This article will review the use of gradients and arrays in
      tissue engineering and biomaterials research, with a focus on cellular and
      biologic responses.

PMID- 19601754
TI  - Combinatorial approaches to controlling cell behaviour and tissue formation in 3D
      via rapid-prototyping and smart scaffold design.
AB  - The understanding of fundamental phenomena involved in tissue engineering and
      regenerative medicine is continuously growing and leads to the demand for three
      dimensional (3D) models that better represent tissue architecture and direct
      cells into the proper lineage for specific tissue repair. Porous 3D scaffolds are
      used in tissue engineering as templates to allow cell attachment and tissue
      formation. Scaffold design plays a central role in guiding cells to synthesize
      and maintain new tissues. While a number of techniques have been developed and
      are now in use for high-throughput screening of combinatorial factors involved in
      biotechnology in two-dimensions, high-throughput screening in 3D is still in its
      infancy. There is a broad interest in developing similar techniques to assess
      which variables are critical in designing 3D scaffolds to achieve proper and
      lasting tissue regeneration. We describe, herein, a number of studies adopting
      smart scaffold design and in vitro and in vivo analysis as the basis for 3D model
      systems for evaluating combinatorial factors influencing cell differentiation and
      tissue formation.

PMID- 19601755
TI  - Assays for eukaryotic cell chemotaxis.
AB  - Chemotaxis is essential for many biological processes. Much of our understanding
      of the mechanisms underlying chemotaxis is based on a variety of in vitro assays.
      We review these assays, dividing them into groups depending on the process used
      to generate the gradient. We describe how each method works, its strengths and
      limitations, and provide some information about the kinds of cells that have been
      studied with each assay.

PMID- 19601753
TI  - High throughput optimization of stem cell microenvironments.
AB  - Stem cells have great potential as cell sources for regenerative medicine due to
      both their self-renewal and multi-lineage differentiation capacity. Despite
      advances in the field of stem cell biology, major challenges remain before stem
      cells can be widely used for therapeutic purposes. One challenge is to develop
      reproducible methods to control stem cell growth and differentiation. The niche
      in which stem cells reside is a complex, multi-factorial environment. In contrast
      to using cells alone, biomaterials can provide initial structural support, and
      allow cells to adhere, proliferate and differentiate in a three-dimensional
      environment. Researchers have incorporated signals into the biomaterials that can
      promote desired cell functions in a spatially and temporally controlled manner.
      Despite progress in biomaterial design and methods to modulate cellular behavior,
      many of the complex signal networks that regulate cell-material interactions
      remain unclear. Due to the vast numbers of material properties to be explored and
      the complexity of cell-surface interactions, it is often difficult to optimize
      stem cell microenvironments using conventional, iterative approaches. To address
      these challenges, high throughput screening of combinatorial libraries has
      emerged as a novel approach to achieve rapid screening with reduced materials and
      costs. In this review, we discuss recent research in the area of high throughput
      approaches for characterization and optimization of cellular interactions with
      their microenvironments. In contrast to conventional approaches, screening
      combinatorial libraries can result in the discovery of unexpected material
      solutions to these complex problems.

PMID- 19601756
TI  - Biomimetic stratified scaffold design for ligament-to-bone interface tissue
      engineering.
AB  - The emphasis in the field of orthopaedic tissue engineering is on imparting
      biomimetic functionality to tissue engineered bone or soft tissue grafts and
      enabling their translation to the clinic. A significant challenge in achieving
      extended graft functionality is engineering the biological fixation of these
      grafts with each other as well as with the host environment. Biological fixation
      will require re-establishment of the structure-function relationship inherent at
      the native soft tissue-to-bone interface on these tissue engineered grafts. To
      this end, strategic biomimicry must be incorporated into advanced scaffold
      design. To facilitate integration between distinct tissue types (e.g., bone with
      soft tissues such as cartilage, ligament, or tendon), a stratified or multi
      phasic scaffold with distinct yet continuous tissue regions is required to pre
      engineer the interface between bone and soft tissues. Using the ACL-to-bone
      interface as a model system, this review outlines the strategies for stratified
      scaffold design for interface tissue engineering, focusing on identifying the
      relevant design parameters derived from an understanding of the structure
      function relationship inherent at the soft-to-hard tissue interface. The design
      approach centers on first addressing the challenge of soft tissue-to-bone
      integration ex vivo, and then subsequently focusing on the relatively less
      difficult task of bone-to-bone integration in vivo. In addition, we will review
      stratified scaffold design aimed at exercising spatial control over heterotypic
      cellular interactions, which are critical for facilitating the formation and
      maintenance of distinct yet continuous multi-tissue regions. Finally, potential
      challenges and future directions in this emerging area of advanced scaffold
      design will be discussed.

PMID- 19601757
TI  - Haptotactic gradients for directed cell migration: stimulation and inhibition
      using soluble factors.
AB  - A recently developed technique for the measurement of cell migration on surface
      bound gradients was used to assay the behavior of microvascular endothelial cells
      on a range of fibronectin gradient slopes in the presence of soluble promoters
      and inhibitors of chemotaxis. Directional microvascular endothelial cell
      migration was shown to increase with increasing gradient slope with no
      significant change in cellular persistence time or random cell speed. Uniformly
      distributed soluble chemotactic factor in the hMEC growth media enhanced
      directional migration. The addition of migration-inhibiting LY294002 eliminated
      the directional component of cell migration at a 5 microM dosing. These
      experiments broaden the understanding of the directional nature of cell motion
      and present a reliable system for the quantitative study of cell migration in
      complex conditions in vitro.

PMID- 19601758
TI  - Inkjet printing of growth factor concentration gradients and combinatorial arrays
      immobilized on biologically-relevant substrates.
AB  - Current methods for engineering immobilized, 'solid-phase' growth factor patterns
      have not addressed the need for presentation of the growth factors in a
      biologically-relevant context. We developed an inkjet printing methodology for
      creating solid-phase patterns of unmodified growth factors on native biological
      material substrates. We demonstrate this approach by printing gradients of
      fluorescently labeled bone morphogenetic protein-2 (BMP-2) and insulin-like
      growth factor-II (IGF-II) bio-inks on fibrin-coated surfaces. Concentration
      gradients were created by overprinting individual substrate locations using a
      dilute bio-ink to modulate the surface concentration of deposited growth factor.
      Persistence studies using fluorescently-labeled BMP-2 verified that the gradients
      retained their shape for up to 7 days. Desorption experiments performed with
      (125)I-BMP-2 and (125)I-IGF-II were used to quantify the surface concentration of
      growth factor retained on the substrate for up to 10 days in serum containing
      media after rinsing of the unbound growth factor. The inkjet method is
      programmable so the gradient shape can be easily modified as demonstrated by
      printed linear gradients with varying slopes and exponential gradients. In
      addition, the versatility of this method enabled combinatorial arrays of multiple
      growth factors to be created by printing overlapping patterns. The overlapping
      printing method was used to create a combinatorial square pattern array
      consisting of various surface concentrations of BMP-2 and fibroblast growth
      factor-2 (FGF-2). C2C12 myogenic precursor cells were seeded on the arrays and
      alkaline phosphatase staining was performed to determine the effect of FGF-2 and
      BMP-2 surface concentration on guiding C2C12 cells towards an osteogenic lineage.
      These results demonstrate the utility of inkjet printing for creating orthogonal
      growth factor gradients to investigate how combinations of immobilized growth
      factors influence cell fate.

PMID- 19601759
TI  - Quantification of cell response to polymeric composites using a two-dimensional
      gradient platform.
AB  - A simple and straightforward screening process to assess the toxicity and
      corresponding cell response of dental composites would be useful prior to
      extensive in vitro or in vivo characterization. To this end, gradient composite
      samples were prepared with variations in filler content/type and in degree of
      conversion (DC). The DC was determined using near infrared spectroscopy (NIR),
      and the surface morphology was evaluated by laser scanning confocal microscopy
      (LSCM). RAW 264.7 macrophage-like cells were cultured directly on the composite
      gradient samples, and cell viability, density, and area were measured at 24 h.
      All three measures of cell response varied as a function of material properties.
      For instance, compositions with higher filler content had no reduction in cell
      viability or cell density, even at low conversions of 52%, whereas significant
      decreases in viability and density were present when the filler content was 35%
      or below (by mass). The overall results demonstrate the complexity of the cell
      material interactions, with properties including DC, filler type, filler mass
      ratio, and surface morphology influencing the cell response. The combinatorial
      approach described herein enables simultaneous screening of multiple compositions
      and material properties, providing a more thorough characterization of cell
      response for the improved selection of biocompatible composite formulations and
      processing conditions.

PMID- 19601761
TI  - Developmental genes and cancer.

PMID- 19601760
TI  - Local histogram analysis: detecting cell-microstructure interactions on
      combinatorial biomaterial libraries.
AB  - Increasingly, combinatorial libraries are used to screen large numbers of complex
      chemically- and physically-patterned polymers against cell response. There is a
      strong need to extract meaningful relationships between cell function and
      material surface features from these experiments. A novel high-throughput cell
      material screening strategy, based upon local cell-feature analysis (LCFA) was
      applied to screen osteoblast proliferation behavior on combinatorial libraries of
      phase-separated PLGA and PCL. Traditional factor importance analysis, which uses
      summary statistical inference to identify significant variables, indicated that
      one controlling material surface feature was PCL diameter. However, the summary
      statistic analysis was unable to uncover more subtle relationships. The LCFA
      method, based on histograms of distances between cells and microstructures, was
      able to identify non-linear, discrete relationships between proliferation, PCL
      diameter, and cell-PCL distance. LCFA provides an advantage in that a
      distribution function is not assumed, but rather is developed from the data.
      Using these results, we propose a model for classifying the material
      microstructure interactions, in which small PCL islands far from the cell nucleus
      act as holders for attachment and large islands close to cells act to shape the
      cell.

PMID- 19601763
TI  - Myc--what we have learned from flies.
AB  - The Myc family proteins are key regulators of animal growth and development.
      dMyc, the only Drosophila member of the Myc gene family, is orthologous to the
      mammalian c-Myc oncoprotein. Extensive studies have revealed much about both
      upstream regulators and downstream target genes in the sphere of Myc regulation.
      Here, we review some of the critical discoveries made using the Drosophila model,
      in particular those studies that have explored the essential role of the Myc
      family in growth and cell cycle progression and identified many of the upstream
      signals and downstream targets common to both c-Myc and dMyc.

PMID- 19601762
TI  - The rb pathway and cancer therapeutics.
AB  - The retinoblastoma gene, Rb, was originally identified as the tumor suppressor
      gene mutated in a rare childhood cancer called retinoblastoma (reviewed in [1]).
      Subsequent studies showed that Rb functions in a pathway that is often
      functionally inactivated in a large majority of human cancers. Interestingly,
      recent studies showed that in certain types of cancers, Rb function is actually
      required for cancer development. The intimate link between the Rb pathway and
      cancer development suggests that the status of Rb activity can potentially be
      used to develop targeted therapy. However, a prerequisite will be to understand
      the role of Rb and its interaction with other signaling pathways in cancer
      development. In this review, we will discuss the roles of Rb in proliferation,
      apoptosis and differentiation by reviewing the recent findings in both mammalian
      systems and different model organisms. In addition, we will discuss strategies
      that can be employed that specifically target cancer cells based on the status of
      the Rb pathway.

PMID- 19601765
TI  - Semaphorins at the interface of development and cancer.
AB  - Semaphorins (Semas), a family of evolutionarily conserved secreted and
      transmembrane proteins, were initially identified as axon guidance regulators and
      have since been implicated in the development of a number of other tissues. Sema
      signaling also regulates a variety of processes that are linked to cancer (i.e.
      metastasis, cell migration, cell growth). The mechanisms by which Sema signaling
      regulates axonogenesis and tumorigenesis are strikingly similar, making advances
      in either field applicable to the alternate discipline. Here, recent advances in
      understanding the roles of Semas in development and cancer, as well as the
      therapeutic potential for targeting this signaling pathway in human cancers, are
      reviewed.

PMID- 19601766
TI  - Functional genomic approaches targeting the wnt signaling network.
AB  - The sequencing of whole genomes, including those of model organisms, has provided
      an unprecedented resource to the research community to make sense of the genetic
      code. However, it is the advent of novel functional genomic technologies that
      have been truly instrumental in bridging the gap between gene sequence and gene
      function. The past few years have witnessed a rapid growth in the development and
      implementation of high-throughput screening (HTS) technologies that researchers
      are now using to discover "gene-function" in an unbiased, systematic, time and
      cost-efficient manner. One of the most promising functional genomic approach that
      has emerged in the past few years is based on RNA-interference (RNAi) in which
      the introduction of double-stranded RNA (dsRNA) or short-interfering RNA (siRNA)
      into cells or whole organisms can effectively suppress endogenous gene
      expression. The RNAi-based screening technology has made it feasible to query the
      function of whole genomes in the regulation of conserved cell-signaling pathways
      and the crosstalk between them in "signaling networks" that are known to
      influence important cell biological functions, such as cell proliferation and
      growth, cell morphology, cell adhesion and cell death. In this review we discuss
      the application, advantages and limitations of RNAi and other post-genomic
      technologies in the identification of novel modulators of cell-signaling
      pathways, with a focus on the Wnt signaling pathway. We also discuss the future
      scope and utility of designing additional variants of these genome-scale screens.

PMID- 19601764
TI  - Netrin and DCC: axon guidance regulators at the intersection of nervous system
      development and cancer.
AB  - In recent years, a number of axon guidance genes, including Netrin (Net) and
      Deleted in Colorectal Cancer (DCC), have been implicated in human cancers. Many
      of the hallmarks of human cancer, such as cell growth, invasion, evasion of
      apoptosis, and formation of a blood supply to the tumor, involve cellular
      processes that are critical during nervous system development. Here, the roles of
      Net-DCC in the regulation of these cellular processes in tumors and developing
      neurons are discussed. The advantages of using Drosophila to study the function
      of Net-DCC and other axon guidance molecules in these cellular processes, as well
      as the potential for cancer therapeutics targeting Net-DCC are highlighted.

PMID- 19601767
TI  - Fibroblast growth factors in development and cancer: insights from the mammary
      and prostate glands.
AB  - The fibroblast growth factor (FGF) family is comprised of 22 ligands that bind
      and activate several FGF receptor (FGFR) isoforms. Critical roles for FGFs and
      FGFRs have been well-established during embryonic development. For example, the
      FGF10/FGFR2IIIb axis has been linked to embryonic development of both the mammary
      and prostate glands, which are the subject of this review. Furthermore, recent
      studies using novel mouse models have suggested that this pathway also
      participates in postnatal development in the mammary and prostate glands. These
      studies have provided novel insights into the mechanisms by which FGFs and FGFRs
      promote ductal outgrowth and branching morphogenesis. In addition to the
      established roles of FGFs in development, aberrant activation of the FGF pathway
      has been linked to tumor progression in both breast and prostate cancer. Recent
      studies have linked FGFR1 expression and single nucleotide polymorphisms in FGFR2
      to breast cancer. Furthermore, novel pre-clinical models have demonstrated the
      ability of FGFRs to promote numerous aspects of breast and prostate cancer.
      Understanding the roles of FGFs in development will provide insights into the
      mechanisms by which deregulation of the FGF pathway leads to tumorigenesis,
      ultimately leading to the development of novel therapeutic strategies designed to
      target this pathway in cancer patients.

PMID- 19601768
TI  - Defining the role of integrin alphavbeta6 in cancer.
AB  - Integrins are a large family of heterodimeric transmembrane receptors that
      mediate cell-substratum adhesion. alphavbeta6 is an epithelial-specific integrin
      that is a receptor for the extracellular matrix (ECM) proteins fibronectin,
      vitronectin, tenascin and the latency associated peptide (LAP) of TGF-beta.
      Integrin alphavbeta6 is not expressed in healthy adult epithelia but is
      upregulated during wound healing and in cancer. alphavbeta6 has been shown to
      modulate invasion, inhibit apoptosis, regulate the expression of matrix
      metalloproteases (MMPs) and activate TGF-beta1. There is increasing evidence,
      primarily from in vitro studies, that suggest that alphavbeta6 may actually
      promote carcinoma progression. In this review we summarize what has been learnt
      in the past few years about the role of alphavbeta6 in cancer progression.

PMID- 19601770
TI  - Medication assisted treatment in the treatment of drug abuse and dependence in
      HIV/AIDS infected drug users.
AB  - Drug use and HIV/AIDS are global public health issues. The World Health
      Organization (WHO) estimates that up to 30% of HIV infections are related to drug
      use and associated behaviors. The intersection, of the twin epidemics of HIV and
      drug/alcohol use, results in difficult medical management issues for the health
      care providers and researchers who work in the expanding global HIV prevention
      and treatment fields. Access to care and treatment, medication adherence to
      multiple therapeutic regimens, and concomitant drug -drug interactions of
      prescribed treatments are difficult barriers for drug users to overcome without
      directed interventions. Injection drug users are frequently disenfranchised from
      medical care and suffer sigma and discrimination creating additional barriers to
      care and treatment for their drug abuse and dependence as well as HIV infection.
      In an increasing number of studies, medication assisted treatment of drug abuse
      and dependence has been shown to be an important HIV prevention intervention.
      Controlling the global transmission of HIV will require further investment in
      evidence-based interventions and programs to enhance access to care and treatment
      of individuals who abuse illicit drugs and alcohol. In this review, we present
      the cumulative evidence of the importance of medication assisted treatment in the
      prevention, care, and treatment of HIV infected individuals who also abuse drugs
      and alcohol.

PMID- 19601769
TI  - Neurodegeneration in Niemann-Pick Type C disease and Huntington's disease: impact
      of defects in membrane trafficking.
AB  - Although neurodegenerative diseases exhibit distinct pathologies, such as
      affected neuronal cell population, age of onset, and pathological symptoms,
      overlapping characteristics can be observed at the cellular level. In particular,
      several neurodegenerative diseases display defects in intracellular vesicular
      trafficking. Here we discuss the range of cellular phenotypes observed in two
      rare neurodegenerative diseases, Niemann-Pick Type C and Huntington's Disease,
      both of which involve vesicular trafficking defects that may contribute to
      neuronal cell death. In NPC, the primary defect is cholesterol and
      glycosphingolipid accumulation, but NPC mutant cells display widespread
      trafficking alterations. In HD, protein aggregates are a hallmark feature, but HD
      cells also exhibit changes in vesicular traffic, including axonal transport and
      early endosomal trafficking, that likely impact neuronal cell viability. Here we
      discuss current therapies that seek to address cellular defects in NPC and HD and
      describe areas of investigation that may lead to new therapeutic treatment.

PMID- 19601771
TI  - The changing face of HIV/AIDS in treated patients.
AB  - The spectrum of complications emerging in successfully treated HIV-infected
      patients has dramatically changed since the advent of HAART. Typical AIDS
      defining illnesses have been substituted by new comorbid conditions that threaten
      even those patients who maintain virologic suppression. Proper management of
      cardiovascular risk, and early diagnosis of AIDS-related and, particularly, non
      AIDS-related malignancies (including papilomavirus-related neoplasms) must be
      introduced into the routine of care. Hot areas of investigation include HIV
      associated neurocognitive disorders, hepatitis B and C coinfection, non-alcoholic
      fatty liver disease, progressive multifocal leukoencephalopathy and tuberculosis.
      Bone and kidney long-term toxicities and lipoatrophy remain as issues of
      paramount importance. The identification and early treatment of immune
      reconstitution disease is also of major interest, specially in those patients
      starting their antiretroviral treatment with severe CD4 cell depletion. The
      present review focuses on these twelve areas of increasing interest for
      physicians currently facing successfully treated HIV+ patients.

PMID- 19601772
TI  - Immunoglobulin G-reactive antibodies from sera of healthy individuals enriched in
      IgG2--therapeutic potential in HIV-1 infection.
AB  - OBJECTIVE: To characterize the functional properties of natural autoantibodies
      capable of preventing in vitro infection by HIV-1, present in normal human serum
      (NHS), and denoted as IgG-reactive antibodies. METHODS: IgG-reactive antibodies
      were affinity purified both from normal human serum (NHS) and from a GammaBind G
      Sepharose Flowthrough (GBF) fraction of NHS by affinity chromatography on IgG
      coupled to CNBr-activated Sepharose (IgG-Sepharose). RESULTS: The GBF fraction
      was shown, by Capture ELISA relative to isotype-matched standards, to contain in
      addition to IgM and IgA isotypes, a low but constant level of IgG isotype. About
      15% of the GBF fraction's IgG, compared to only about 0.3% of the NHS IgG, was
      affinity purified on IgG-Sepharose. On IgG subclass analysis, in contrast to the
      characteristic dominance of IgG1 in pooled NHS, the IgG-reactive antibodies
      obtained from NHS and from the GBF fraction each showed a dominance of IgG2.
      Western blot analysis confirmed the abundance of IgG2, a major IgG subclass
      reactive against carbohydrate antigens, and showed the presence of IgG2 dimers.
      The IgG-reactive antibodies separated from the GBF fraction were able to
      neutralize HIV-1(BaL) strain with approaching 100% and 80% effectiveness at 2
      microg/ml and 0.6 microg/ml, respectively, as well as the primary isolates HIV
      1(NDK) (X4-tropic isolate) and HIV-1(JR-CSF) (R5-tropic isolate) with an IC50
      between 0.4 microg/ml and 1.8 microg/ml for two different preparations.
      CONCLUSION: These findings further support our previous proposal for IgG-reactive
      antibody preparations to be used in the treatment of HIV-1 infected individuals.

PMID- 19601773
TI  - Molecular phenotype of CXCL12beta 3'UTR G801A polymorphism (rs1801157) associated
      to HIV-1 disease progression.
AB  - OBJECTIVE: To investigate the molecular phenotype of the AIDS-onset delaying
      polymorphism in CXCL12beta 3'UTR (rs1801157). METHODS: The 3 UTRs of the
      CXCL12beta isoform containing the A or G polymorphic variants were cloned
      downstream of the Luciferase gene under the control of the CXCL12 promoter. The
      plasmids were transfected in U373 and LC5 cells and the polymorphism phenotype
      was evaluated in terms of Luciferase activity and mRNA stability. RESULTS: The
      3'A genotype compared to 3'G leads to an increased luciferase activity in
      unstimulated and PMA+Ionomycin treated cells both in astrocytes (p = 0,0002, p =
      0,02) and fibroblasts (p = 0,002, p = 0,03). The mRNA containing the 3'A variant
      have two-fold longer half-life compared to the 3'G variant (p = 6,99E(-7)).
      CONCLUSIONS: CXCL12beta 3'A polymorphism, previously associated with resistance
      to AIDS progression and other diseases, leads to increased levels of CXCL12 mRNA,
      the results presented here demonstrate that this effect is a consequence of an
      enhanced mRNA stability. Our data contribute to characterize the CXCL12 as a
      potential pharmacological target in AIDS, autoimmune diseases and cancer.

PMID- 19601775
TI  - Pre-screening HIV-1 reverse transcriptase resistance mutations in subtype B
      patients using a novel multiplex primer extension assay.
AB  - Antiretroviral therapy is standard treatment for HIV-infected patients. Such
      therapy has decreased mortality and morbidity, but treatment success is often
      jeopardized by the emergence of viral drug resistance. Moreover, in recent years
      there has been a reported rise in the incidence of transmitted drug resistance,
      highlighting the importance of pre-treatment resistance screening. In this
      report, we describe the development and utility of a sensitive multiplex approach
      for detecting mutations conferring drug resistance to HIV-1 reverse transcriptase
      inhibitors. This protocol, termed HIV-SNaPshot, utilizes a multiplex primer
      extension assay with capillary electrophoresis reporting altered nucleotides at
      nine important drug resistance mutation positions. Mutations were successfully
      detected to levels of 5% in viral quasispecies populations. Furthermore, although
      developed and optimised for HIV-1 subtype B, drug resistance mutations could also
      be detected in most non-B subtypes. Comparison of the HIV-SNaPshot with the
      commercial Viroseq genotyping system in 10 patients gave similar results, but
      importantly, additional resistance mutations were identified in several patients
      by the HIV-SNaPshot assay. Thus, the HIV-SNaPshot is a method capable to support
      standard genotyping for the determination of minority HIV-1 resistance mutations,
      with equivalent and perhaps greater sensitivity than Viroseq.

PMID- 19601774
TI  - Projecting dynamic trends for HIV/AIDS in a highly endemic area of China:
      estimation models for Liangshan Prefecture, Sichuan Province.
AB  - This study describes the current situation and projects dynamic trends for HIV
      prevalence in a highly endemic area of China, Liangshan Prefecture, Sichuan
      Province. Epidemiological, behavioral, and population census data from multiple
      sources were analyzed to extract input for an Asian Epidemic Model (AEM). Fitting
      curves to historical trends in HIV prevalence were used as a baseline, and future
      intervention scenarios were explored using the AEM. For 2007, modeled data
      suggested approximately 0.5% adult HIV prevalence in Liangshan, with an estimated
      17,450 people living with HIV/AIDS and 3,400 new infections. With current high
      risk behaviors, the model predicts that adult prevalence will rise to 1.5% by
      2020. Increased condom use and clean needle exchange among injection drug users
      (IDUs) have slowed the epidemic. The source of new HIV infections will change
      from a preponderance of IDU-related infections in 2007 (65.9%) to a mixed
      epidemic in 2020 (general population heterosexuals 45.2%, IDU 38.6%, homosexual
      transmission between men 12.7%, female sex workers and their clients 3.5%). We
      anticipate rising prevalence, stable incidence, and higher representation of
      sexual transmission over time. Prevention investments should target specific
      interventions toward sub-groups at highest risk, given that both IDUs and men who
      have sex with men will likely represent a majority of cases and serve as a bridge
      population.

PMID- 19601776
TI  - Trends and economic stress: a challenge to universal access to antiretroviral
      treatment in India.
AB  - The prospects for expanded access to antiretroviral therapy (ART) in resource
      poor settings have greatly improved as a result of global and national efforts to
      reduce the cost of antiretroviral drugs (ARV), growing availability of cheaper
      generics, and increased financing available from the Global Funds like Medicines
      Sans Frontieres. Indian health set-up provides drugs free-of-cost to HIV infected
      patients through government network and also through open-market to those who
      intend to have personalized care. Post-2005, implementation of WTO agreement on
      TRIPS is expected to have a significant impact on pricing and availability of
      generic ARV. The study has been planned to explore the trends and gaps in
      availability & accessibility of ARV in India. The trends in per-patient-per-year
      (PPPY) cost of individual ARV and treatment regimes were also explored. The
      epidemiological data demonstrated stabilization of the epidemic in India. Most
      ARV are available in India by the generic manufacturers with a median drug lag
      period of 2.05 years (Range 0.75-6.51 years). There is a significant price
      difference in drugs available from generic and originator companies. Prices for
      patented and generic ARV in India reflect price negotiations that have taken
      place since the introduction of drugs in the country, still most of the ARVs are
      available at a much higher cost in the market [median 2.6 times (range 1-7)]. The
      per-patient per year (PPPY) cost of providing first-line regime in 2008 has
      decreased 2.75 times from that in 2003. The analysis shows the stabilization of
      prices of all drugs after 2006. HIV spending in India has seen a growth of 26
      percent and 28 percent in 2005-06 and 2006-07 respectively. Still, the expected
      expenditure to cover the whole patient population needing therapy is considerably
      higher than the actual expenditure incurred for providing ARV. Despite the price
      reductions and availability of ARV at a lower cost through agencies like MSF,
      there is a large gap in the expenditure incurred and patient population covered.
      These trends may foreshadow future AIDS treatment cost trends in the country as
      more people start treatment, AIDS patients live longer and move from first-line
      to second and third-line treatment, AIDS treatment becomes more complex, generic
      competition emerges, and newer patented drugs become available.

PMID- 19601777
TI  - Presence of HIV-1 DNA in spermatozoa from HIV-positive patients: changes in the
      semen parameters.
AB  - Although very inefficient, sexual transmission of HIV-1 is responsible for more
      than 80% of infections worldwide. Yet, the presence of HIV in spermatozoa has
      been a matter of debate. The aim of this study was to evaluate the presence of
      HIV nucleic acids and the distribution of mannose receptors in sperm cells, and
      to determine the semen parameters and cytokine levels in ejaculates from HIV
      positive patients. The presence of non-seminal cells in purified sperm was
      revealed by light microscopy, flow cytometry and RT-PCR. HIV nucleic acids were
      evaluated by nested PCR; the distributions of mannose receptors on the surface of
      the sperm and cytokine levels in ejaculates were determined by fluorescence
      microscopy and flow cytometry respectively. Sperm characteristics were determined
      by conventional methods. HIV DNA was detected in 69.2% of purified sperm from HIV
      positive men; in contrast all purified sperm were negative for HIV RNA. The
      distribution of mannose receptors and cytokine levels in HIV-1-positive men were
      similar to uninfected individuals. Using the Principal Component Analysis (PCA)
      method, it was possible to determine that semen parameters of HIV-positive men
      exhibit different distributions compared to HIV-negative individuals. Finally,
      these results indicate that viral DNA is present in purified sperm from HIV
      positive men and that HIV infection of spermatozoa could be associated with lower
      seminal parameters as demonstrated by the PCA method. The similar distribution of
      mannose receptors between infected and uninfected individuals suggests that sperm
      cells from infected individuals interact normally with oocytes.

PMID- 19601778
TI  - Clinical validation and applicability of different tipranavir/ritonavir genotypic
      scores in HIV-1 protease inhibitor-experienced patients.
AB  - Tipranavir, a non-peptidic protease inhibitor which shows in vitro efficacy
      against some HIV-1-resistant strains, can be used in salvage therapies for multi
      experienced HIV patients due to its peculiar resistance profile including 21
      mutations at 16 protease positions according to International AIDS Society (IAS).
      Other genotypic scores, however, which attribute a different weight to single
      amino-acid substitutions, have been recently proposed. To validate the clinical
      utility of four different genotypic scores for selecting tipranavir responders,
      the baseline resistance pattern of 176 HIV heavily experienced patients was
      correlated with virological success (HIV-RNA<50 copies/ml) after 24 weeks of a
      new treatment based on tipranavir/ritonavir. Virological suppression after 24
      weeks was reached by 42.5% of patients. With univariate analysis, genotypic
      scores were all associated with outcome but showed a low accuracy with ROC
      analysis, with the weighted score (WS) by Scherer et al. demonstrating the best
      performance with an AUC of 68%. Only 52% of patients classified as susceptible
      (WS< or =3) responded to the new therapy. The following variables were
      significantly associated (p<0.05) to failure with multivariate analysis: WS, log
      peak of HIV-RNA, IAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES.
      On the contrary, the use of T20 in T20-naive patients and the V82AFSI and F53LY
      non-IAS mutations were associated with virological success. The study suggests
      that even if the "weighted" scores are able to interpret correctly the
      antiretroviral resistance profile of multi-experienced patients, it is difficult
      to individuate a cut-off which can be easily applied to this population for
      discriminating responders.

PMID- 19601779
TI  - Successfully resuscitated sudden cardiac death in a young homosexual male with
      HIV myocarditis.
AB  - Successfully treated sudden cardiac death due to malignant arrhythmia related to
      HIV myocarditis in a young male with favorable clinical and virological profile
      is not described in current literature. HIV myocarditis as a possible cause of
      malignant ventricular arrhythmia and sudden cardiac death is discussed.

PMID- 19601780
TI  - CD8+ cell noncytotoxic antiviral response in long-term HIV-1 infected former
      blood donors in China.
AB  - Most of the HIV-infected long term survivors show strong CD8+ cell noncytotoxic
      antiviral response (CNAR) that plays as an important factor for maintaining the
      relative healthy state of infected individuals. HIV infected former blood donors
      (FBDs) in Anhui, China are the unique population that considered infected by the
      same or a related HIV strain by the same exposure route, and is better to be
      studied for viral and host immunological factors associated with disease
      progression, such as CNAR. We examined CNAR in 63 asymptomatic untreated HIV
      infected FBDs with different CD4+ cell counts and plasma viral loads. The average
      CD8+ : CD4+ cell ratio to reach 90% suppression of HIV replication in the groups
      with CD4+ cell counts of >500, 300-500 and <300 cells/microl were 0.85 : 1, 1.47
      : 1 and 1.88 : 1 respectively (P<0.0001). The average CD8+ : CD4+ cell ratio to
      reach 90% suppression of HIV replication was 1.07 : 1 and 1.66 : 1 in the group
      with plasma viral load of <30,000 and >30,000 RNA copy/ml respectively
      (P=0.0002). The results indicated that CNAR activity in long-term HIV-1 infected
      FBDs correlates directly with CD4+ cell counts, and correlates reversely with
      plasma viral loads. Our findings in long term infected FBDs confirm the clinical
      relevancy of CNAR and suggest that CNAR could be an additional marker to help
      determine the optimal time for starting therapy in HIV infected person.

PMID- 19601781
TI  - Impact of prior HAART use on clinical outcomes in a large Kenyan HIV treatment
      program.
AB  - BACKGROUND: HIV treatment programs in Africa typically approach all enrolling
      patients uniformly. Growing numbers of patients are antiretroviral experienced.
      Defining patients on the basis of antiretroviral experience may inform enrollment
      practices, particularly if medical outcomes differ. METHODS: Baseline and follow
      up measures (CD4, weight change, and survival) were compared in a retrospective
      analysis between antiretroviral-naive (ARV-N) and antiretroviral experience (ARV
      E) patients enrolled at the Coptic Hope Center for Infectious Diseases in
      Nairobi, Kenya and followed between January 2004 and August 2006. RESULTS: 1,307
      ARV-N and 962 ARV-E patients receiving highly active antiretroviral therapy
      (HAART) were followed for median of 9 months (interquartile range: 4-16 months).
      Compared to ARV-N, ARV-E had substantially higher CD4 count (median cells/mm(3),
      193 versus 95, P < 0.001) and weight (median kg, 62 versus 57, P < 0.001) at
      baseline, and lower rates of change in CD4 (-9.2 cells/mm(3)/month; 95% CI, -11.4
      -7.0) and weight (-0.24 kg/month; 95% CI, -0.35 - -0.14) over 12 months.
      Mortality was significantly higher in ARV-N than ARV-E (P = 0.001). CONCLUSIONS:
      ARV-E patients form a growing group that differs significantly from ARV-N
      patients and requires a distinct approach from ARV-N clients. Systematic
      approaches to streamline care of ARV-E patients may allow focused attention on
      early ARV-N clients whose mortality risks are substantially higher.

PMID- 19601783
TI  - Dietary intake in HIV-infected men with lipodystrophy: relationships with body
      composition, visceral fat, lipid, glucose and adipokine metabolism.
AB  - Highly active antiretroviral therapy (HAART) for HIV-infection is associated with
      lipodystrophy, insulin resistance, increased prevalence of disturbances in
      glucose tolerance and diabetes, hyperlipidemia and increased cardiovascular risk.
      Whether dietary intake influences total body fat, visceral fat, insulin
      resistance, glucose metabolism, lipid metabolism and circulating inflammatory
      markers in HIV-infected subjects with lipodystrophy is unclear and the focus of
      this report. We examined the dietary intake of 106 male HIV-infected HAART
      recipients with lipodystrophy, enrolled in a study of the effects of
      rosiglitazone. All subjects had normal glucose tolerance. Dietary intakes were
      determined at study entry using Food Frequency Questionnaires and examined cross
      sectionally against body composition by dual-energy Xray absorptiometry, visceral
      obesity by computed tomography, fasting glucose, insulin, lipids, adiponectin,
      leptin, insulin resistance (by HOMA). Energy underreporters were identified and
      excluded. After exclusion of underreporters (n = 22) we found no relationships
      between diet composition (% dietary fat, %carbohydrate) and BMI, %body fat and
      visceral adiposity (p>0.3). Only modest relationships were found between BMI and
      fat subtypes: polyunsaturated fats (g/day) (r = 0.14, p = 0.007), monounsaturated
      fat (g/d) (r = 0.06, p = 0.001), saturated fat (g/d) (r = 0.02, p<0.0001). Only
      saturated fat related to % total body fat (g/d: r = 0.08, p<0.0001, %energy
      intake: r = 0.16, p<0.0001). No nutrient related to visceral adiposity by CT.
      Dietary fat intake (expressed as a % of energy intake) was not related to total
      cholesterol, HDL cholesterol, triglycerides, fasting insulin, glucose, leptin,
      adiponectin or HOMA-IR (p>0.4). Fat subtype did not relate to fasting insulin,
      insulin resistance, total cholesterol, HDL, triglycerides, glucose, adiponectin.
      In conclusion, there are weak relationships between saturated fat intake and
      adiposity in HIV-infected subjects with lipodystrophy, using gold standard
      measures of body fat. There were no relationships between nutrient intake and
      visceral adiposity, any measure of glucose metabolism, insulin resistance or
      adipokines. Only interventional, prospective studies will determine whether any
      nutritional strategy can assist in ameliorating the metabolic complications
      associated with HIV lipodystrophy.

PMID- 19601782
TI  - Predictability of sustained virological response to pegylated interferon alpha-2b
      Plus ribavirin therapy by week-8 viral response in HIV-positive patients with
      chronic hepatitis C virus infection.
AB  - Chronic hepatitis C is frequent and aggressive in HIV-positive patients.
      Identification of early predictors of response to anti-HCV therapy is needed for
      a lower rate of response and higher discontinuations, compared to HCV mono
      infected subjects. The aim of our study was to evaluate the predictive value of
      virological response (VR) at week 4-8-12 of Pegylated interferon alpha-2b (PEG
      IFN) plus ribavirin (RBV) on sustained virological response (SVR) in HIV-HCV co
      infected patients. 100 patients were treated with PEG-IFN (1.5 mcg/Kg/w) plus RBV
      (> or =10.6 mg/kg/d) and randomized for 24-48 or 48-72 weeks, respectively for
      genotype 2-3 and 1-4, in case of response (HCV-RNA PCR negativity) at the end of
      standard therapy (24 weeks for genotype 2-3, 48 weeks for genotype 1-4).
      Transcription-Mediated Amplification (TMA) assay for HCV-RNA was also applied. 27
      patients reached end-of-treatment response (9 genotype 1-4, 18 genotype 2-3), 21
      achieved SVR (8 genotype 1-4, 13 genotype 2-3). 35 patients dropped, 15 due to
      side-effects. SVR was statistically related to lower baseline HCV-RNA and to VR
      at week 4-8-12, with PPV 64%, 53% and 58%, and NPV 81%, 96% and 88%,
      respectively. In 27 patients, TMA was performed and confirmed standard PCR,
      except in two cases of relapse, who were PCR negative but TMA positive at week
      12. In conclusion, VR at week 8 showed the highest NPV on SVR (96%). The study of
      viral kinetics requires further investigations in HIV-positive patients to
      guarantee a cost-effective therapy and to guide individually the duration of
      treatment. In this setting, TMA might be useful.

PMID- 19601785
TI  - Strategies to improve the efficacy of platinum compounds.
AB  - Platinum drugs are widely used in antitumour therapy and are a cornerstone of the
      treatment of different solid tumours. The pharmacological interest of cisplatin
      has led to the design of many analogues to broaden the spectrum of activity,
      reduce side effects, and overcome resistance. Although the cis configuration was
      initially identified as the only active one, trans-platinum complexes have shown
      significant antitumour activity in preclinical models. In addition to mononuclear
      platinum compounds, multinuclear platinum complexes have been generated that are
      characterised by a different mode of interaction with DNA. Since a major
      limitation to the clinical efficacy of platinum compounds is drug resistance, the
      most important feature of nonconventional platinum drugs should be the capability
      of overcoming cellular resistance. However, due to the multifactorial nature of
      clinical resistance, which also involves pharmacological factors, the
      optimisation of current platinum-based therapy also includes the development of
      drug delivery approaches. The present review focuses on recent studies on the
      molecular alterations of tumour cells that are associated with resistance to
      platinum drugs, the development of novel platinum drugs, and approaches that may
      contribute to improve the efficacy of platinum-based therapy.

PMID- 19601784
TI  - How do HIV-infected smokers react to cigarette price increases? Evidence from the
      APROCO-COPILOTE-ANRS CO8 Cohort.
AB  - BACKGROUND: Smoking prevalence is very high among people living with HIV/AIDS,
      and smoking is riskier for them than for HIV-seronegative people. Promoting
      smoking cessation among HIV-infected people is therefore an emerging public
      health priority. Raising cigarette prices is usually considered as one of the
      most effective ways to reduce smoking, but its effectiveness has never been
      studied among HIV-infected smokers. METHODS: We studied the impact of cigarette
      price increases among HIV-infected smokers, with data extracted from the French
      cohort study APROCO-COPILOTE conducted between 1997 and 2007 among 1,146
      patients. Data regarding respondents' smoking status was collected every 8 months
      over the first 5 years, and every 12 months thereafter. RESULTS: We found
      striking differences across transmission groups regarding socio-demographic
      background and smoking prevalence. The Intravenous Drug Use (IDU) group was
      characterised by a lower socioeconomic status, a higher smoking prevalence and a
      smaller decrease in this prevalence over the period 1997-2007. The homosexual
      group had a higher socioeconomic status, an intermediate smoking prevalence in
      1997, and the highest rate of smoking decrease. In the dynamic multivariate
      analysis, smoking remained correlated with indicators of socioeconomic
      disadvantage and with infection through IDU. Aging and cigarette price increase
      had a negative impact on smoking among the homosexual group, but not for the IDU
      group. CONCLUSION: Among seropositive people, just as for the general population,
      poor smokers are poor quitters. Public health authorities should consider
      interventions which are not smoking-specific, but which contribute to improve the
      living conditions of the most deprived HIV-infected smokers.

PMID- 19601786
TI  - Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism
      that triggers anti-inflammatory action.
AB  - Shock waves (SW), defined as a sequence of single sonic pulses characterised by
      high peak pressure (100 MPa), a fast rise in pressure (< 10 ns) and a short
      lifecycle (10 micros), are conveyed by an appropriate generator to a specific
      target area at an energy density ranging from 0.03 to 0.11 mJ/mm(2).
      Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up
      kidney stones. During the last ten years, this technique has been successfully
      employed in orthopaedic diseases such as pseudoarthosis, tendinitis, calcarea of
      the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon
      diseases. In particular, treatment of the tendon and muscle tissues was found to
      induce a long-time tissue regeneration effect in addition to having a more
      immediate anthalgic and anti-inflammatory outcome. In keeping with this, an
      increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks
      of ESW treatment. Furthermore, clinical observations indicate an immediate
      increase in blood flow around the treated area. Nevertheless, the biochemical
      mechanisms underlying these effects have yet to be fully elucidated. In the
      present review, we briefly detail the physical properties of ESW and clinical
      cases treated with this therapy. We then go on to describe the possible molecular
      mechanism that triggers the anti-inflammatory action of ESW, focusing on the
      possibility that ESW may modulate endogenous nitric oxide (NO) production either
      under normal or inflammatory conditions. Data on the rapid enhancement of
      endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that
      increased NO levels and the subsequent suppression of NF-kappaB activation may
      account, at least in part, for the clinically beneficial action on tissue
      inflammation.

PMID- 19601787
TI  - Recent advances on the roles of NO in cancer and chronic inflammatory disorders.
AB  - Nitric oxide (NO) is a short-life molecule produced by the enzyme known as the
      nitric oxide synthase (NOS), in a reaction that converts arginine and oxygen into
      citrulline and NO. There are three isoforms of the enzyme: neuronal NOS (nNOS,
      also called NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or
      NOS3). It is now known that each of these isoforms may be expressed in a variety
      of tissues and cell types. This paper is a review of the current knowledge of
      various functions of NO in diseases. We discuss in more detail its role in
      Cancer, the role of NO in myocardial pathophysiology, in central nervous system
      (CNS) pathologies. Other diseases such as inflammation, asthma, in chronic liver
      diseases, inflammatory bowel disease (IBD), arthritis, are also discussed. This
      review also covers the role of NO in cardiovascular, central nervous, pancreas,
      lung, gut, kidney, myoskeletal and chronic liver diseases (CLD). The ubiquitous
      role that the simple gas nitric oxide plays in the body, from maintaining
      vascular homeostasis and fighting infections to acting as a neurotransmitter and
      its role in cancer, has spurred a lot of interest among researchers all over the
      world. Nitric oxide plays an important role in the physiologic modulation of
      coronary artery tone and myocardial function. Nitric oxide from iNOS appears to
      be a key mediator of such glial-induced neuronal death. The high sensitivity of
      neurons to NO is partly due to NO causing inhibition of respiration, rapid
      glutamate release from both astrocytes and neurons, and subsequent excitotoxic
      death of the neurons.

PMID- 19601788
TI  - Progress towards the identification of new aggrecanase inhibitors.
AB  - Degenerative diseases are still a challenging issue in clinical therapy; even
      though in several cases it is possible to treat symptoms, drugs able to block
      disease progression are lacking at present. Osteoarthritis (OA) and Rheumatoid
      Arthritis (RA) are degenerative diseases leading to serious cartilage
      destruction, affecting joint functions and giving rise to restricted movement,
      pain and chronic disability. Current clinical treatment for arthritis is confined
      to Non Steroidal Anti-Inflammatory Drugs (NSAIDs), which are effective in
      treating symptoms but fail to block the progression of the disease. Matrix
      Metalloproteases (MMPs) inhibitors have been clinically studied as possible drugs
      for cartilage degradation prevention. However, their clinical use has been
      limited by severe side-effects. Aggrecan, which plays a fundamental role in
      maintaining the structural and mechanical properties of cartilage, has recently
      been found to be specifically cleaved by "aggrecanases". Aggrecanases are
      multidomain zinc metalloproteases, different from MMPs, which cleave the aggrecan
      within the interglobular domain (IGD). Aggrecan breakdown at this site has been
      found to be crucial for cartilage degradation. These new findings re-addressed
      the interest of the research for new arthritis therapeutic agents focusing on
      aggrecanases rather than on MMPs. This review is meant to provide a critical
      appraisal of the ongoing developments of Zn-chelating and non chelating
      aggrecanase inhibitors, with a particular emphasis on the related structure
      activity relationships (SARs), in the light of the protein structural information
      recently made available.

PMID- 19601789
TI  - Iron chelators in medicinal applications - chemical equilibrium considerations in
      pharmaceutical activity.
AB  - Iron chelators are being examined as a potential class of pharmaceutical agents
      to battle different types of cancer as well as iron overload diseases. In recent
      studies, iron binding species such as desferrioxamine, triapine, tachpyridine,
      Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using
      published chemical equilibrium values (stability constants, equilibrium
      constants), it is argued that an iron chelator cannot competitively remove iron
      from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a
      cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] -->
      [Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using
      circumstantial evidence. It is argued that iron chelators can potentially
      interact with iron from ferritin or iron that has precipitated or flocculated as
      oxyhydroxide under physiological pH's. It is argued that chelators can interfere
      with various physiological processes by binding cations such as Ca(2+), Zn(2+) or
      K(+). A number of siderophores and natural products that have the ability to bind
      Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential
      pharmaceutical activity as chelators. Chemical equilibria between cations and
      pharmaceutical agents, which are rarely quantitated in explaining medicinal
      mechanisms, are used to show that chelators can bind and remove iron and other
      cations from physiologically important systems required for cell survival and
      propagation.

PMID- 19601790
TI  - 2-Arylbenzothiazole as a privileged scaffold in drug discovery.
AB  - Substituted 2-arylbenzothiazoles have emerged in recent years as an important
      pharmacophore in a number of diagnostic and therapeutic settings. Attractive
      features of drug candidates based on this benzothiazole scaffold include their
      synthetic accessibility, and synthetic approaches to 2-arylbenzothiazole-based
      compounds will be reviewed here. Examples of 2-arylbenzothiazoles endowed with
      diagnostic/therapeutic activity include the 2-(4-aminophenyl)benzothiazole
      series, which has a remarkable activity profile in both the potential non
      invasive diagnosis of Alzheimer's disease and as antitumour agents.

PMID- 19601791
TI  - An overview on benzylisoquinoline derivatives with dopaminergic and serotonergic
      activities.
AB  - Dopamine and serotonin are important neurotransmitters in the mammalian central
      nervous system (CNS) involved in numerous physiological and behavioural disorders
      such as schizophrenia, major depression, anxiety, Parkinson's and Huntington's
      diseases, and attention deficit hyperactivity disorder. Several natural and
      synthetic benzylisoquinoline derivatives have displayed affinity for dopamine and
      serotonin receptors in nanomolar or micromolar ranges. This review covers the
      last three decades of dopaminergic and serotonergic activities, and especially
      focuses on structure-activity relationships of natural and synthetic
      benzylisoquinoline derivatives. We have included aporphines, 1
      benzyltetrahydroisoquinolines, bis-benzylisoquinolines, protoberberines,
      cularines and other structural analogues. Further molecular modelling
      calculations have been considered as important tools to not only obtain
      structural information of both neurotransmitter receptors, but to also identify
      their pharmacophore features. The development of selective potential ligands like
      benzylisoquinoline derivatives may help in the therapy of diseases related to CNS
      dysfunction.

PMID- 19601792
TI  - Fentanyl analogs: structure-activity-relationship study.
AB  - Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid
      analgesics. This study was aimed to review the structure-activity-relationship
      (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine
      ring. Pharmacological results show that the groups in position 3 of the
      piperidine ring, which are larger than methyl, severely reduce the analgesic
      potency compared to fentanyl. It is likely that the steric factor alone (i.e.
      voluminosity of the group and cis/trans isomerism), rather than the polarity
      and/or chemical reactivity, plays a crucial role in the analgesic potency of this
      series. Although the duration of action, in general, does not depend on the
      stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such
      as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by
      pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that
      the introduction of a functional group such as 3-carbomethoxy reduces the
      duration of action by altering pharmacokinetic properties. SAR findings obtained
      by evaluating the neurotoxic effects of fentanyl analogs substituted in the
      position 3 of the piperidine ring parallel the SAR findings on analgesia in
      regard to potency and duration of action. This might suggest that similar
      receptors are involved in producing both antinociceptive and neurotoxic effects
      of these drugs. It appears that both the potency and the duration of action in
      the series of fentanyl analogs substituted in position 4 of the piperidine ring
      is influenced only by the steric requirement and not by the chemical nature of
      the substituent.

PMID- 19601794
TI  - Antiviral and virucidal activities of natural products.
AB  - Virus infection is one of the major threats to human health and can be avoided by
      minimizing exposure to infectious viruses. Viral clearance of pharmaceutical
      products and sanitization of skin and mucosal surfaces would reduce such
      exposures. Even with such care, virus infection does occur, requiring effective
      treatments by antiviral or virucidal agents. Natural products, in particular
      ingredients of foods and drinks we normally consume or metabolites present in
      human body at low concentrations, would have advantage over synthetic drugs as
      antiviral agents for safety concerns. For this reason, we have been studying
      natural products for their effects on virus inactivation and growth. Such natural
      products, which we have been focusing, include gallate derivatives, caffeine
      present in coffee, caffeic acid present in coffee and various fruits, ascorbic
      and dehydroascorbic acids and a cell metabolite, arginine. Here we will review
      our work on antiviral and virucidal activities of these compounds and the
      mechanism of their antiviral and virucidal effects.

PMID- 19601793
TI  - Current evaluation of the millennium phytomedicine--ginseng (I): etymology,
      pharmacognosy, phytochemistry, market and regulations.
AB  - The dawning of this millennium broke new ground in life science and technology,
      presented us genomic and proteomic revolution, nanotechnology innovation, and
      high performance liquid chromatography coupled with tandem mass spectrometry
      (LC/MS/MS) used for separating and identifying new chemical entities at pico-, or
      even femto-concentrations. Applications of these high technologies to the
      traditional Chinese medicine (TCM) opened a new chapter in the ancient medicine,
      and prompted us to re-evaluate the thousand-year-old phytomedicine- ginseng from
      current perspectives. We, therefore, collected the latest information (mostly
      within 10 years) on ginseng, and condensed the information into two parts of this
      review serial. The present part covers etymology of ginseng, its pharmacognosy
      (natural origin, physical appearance, chemical properties, and specie
      identification), its cultivation and processing-related metabolic changes in
      active ingredients, standardized analytical methods used for quality control of
      various ginseng products, modern analytical methods used to identify and classify
      more than 100 chemical entities (many were recently unfolded) derived from
      ginseng species and their metabolites. The global markets and production of
      ginseng and relevant government regulations are herein updated to exchange
      information and understandings about current people's uses and cultivation of
      ginseng. The second part of the review serial will classify all these 100
      chemical entities separated from various ginseng species into different groups
      based on their structural similarities, and summarize bioactivities of these
      entities. The second part of the review serial will also focus on recent findings
      of ginseng pharmacology and its clinical trials for various diseases, and brief
      side effects of ginseng.

PMID- 19601795
TI  - Cerebral amyloid angiopathy: a common cause of cerebral hemorrhage.
AB  - Amyloid is a term used to describe protein deposits with circumscript physical
      characteristics: beta-pleated sheet configuration, apple green birefringence
      under polarized light after Congo red staining, fibrillary structure and high
      insolubility. Cerebral amyloid angiopathy (CAA) defines a clinicopathological
      phenomenon characterized by amyloid deposition in the walls of leptomeningeal and
      cortical arteries, arterioles, and, less often capillaries and veins of the
      central nervous system. CAAs are currently classified according to the protein
      deposited including amyloid beta peptide (Abeta), cystatin C (ACys C), prion
      protein (PrP(Sc)), ABri/ADan, transthyretin (ATTR), and gelsolin (AGel). Most
      often amyloid deposition occurs in sporadic forms. In less common hereditary
      forms, a mutated variant protein or precursor protein is abnormally metabolized
      by proteolytic pathways in consequence of specific gene mutations, and
      accumulates as amyloid. The spectrum of clinical phenotypes associated with CAA
      related vasculopathic changes includes both ischemic and hemorrhagic
      presentations, primary intracerebral hemorrhage (PICH) being probably the most
      well-recognized. However, in spite of accumulating data and recent progress in
      understanding the pathogenesis of CAA-related hemorrhage, the exact mechanisms
      leading to vessel rupture in these cases are yet to be established. This
      represents, at present, a major limitation to the identification of reliable
      biomarkers and the development of disease-specific treatment options. The present
      paper summarizes epidemiologic and clinical aspects of CAA, and highlights the
      presumed pathomechanisms of amyloid deposition in both sporadic and hereditary
      forms.

PMID- 19601796
TI  - Preclinical drug discovery for new anti-pneumocystis compounds.
AB  - Pneumocystis remains an important cause of fatal pneumonia (PCP) in HIV patients
      and other immunocompromised hosts. Preclinical drug discovery for agents active
      against PCP has been hindered in large part by the lack of a continuous in vitro
      growth system. Since approval in 1978, the combination of the folic acid
      synthesis inhibitor combination trimethoprim-sulfamethoxazole has been the
      primary agent for prophylaxis and therapy. Short term in vitro assays using cell
      monolayer-based and cell free systems in combination with in vivo studies in
      rodent models of infection have been the mainstay of candidate screening methods.
      These systems and their applications are reviewed here. Most strategies have
      focused on testing compounds already in clinical use, such as dapsone or
      atovaquone, for activity against Pneumocystis alone or in combination, and as
      parent compounds for chemical derivation, such as pentamidine and its analogues.
      Other successes from the bench include primaquine-clindamycin for moderate
      pneumonia and the family of Beta-glucan synthase inhibitors, which hold promise
      for clinical use against PCP. Despite the significant obstacles for drug
      discovery, progress in identifying novel agents has been made with current
      systems and the promise of future new targets is expected with the annotation of
      the Pneumocystis genome.

PMID- 19601797
TI  - Solid phase synthesis of biologically important indoles.
AB  - Combinatorial chemistry has become an important tool in the area of modern drug
      discovery and its success is partly dependent on further advances of solid phase
      organic synthesis (SPOS). Indoles are an important class of compounds with a
      broad spectrum of biological activities. Therefore, considerable attention is
      given for the development of effective methodology for the substituted indoles
      not only in solution phase but also on solid phase. In this review, indole
      forming classical reactions such as Fisher, Nenitzescu, Bartoli, Modified
      Madelung, Modified Bischler, and Wittig type reactions on solid support are
      summarized. In addition, metal mediated cyclizations such as palladium, and
      rhodium catalyzed cyclizations along with microwave-assisted solid phase
      synthesis of indoles have been discussed. Also, the most relevant biological
      properties of indoles have been reported.

PMID- 19601798
TI  - DD-ligases as a potential target for antibiotics: past, present and future.
AB  - DD-ligases catalyze the synthesis of the D-Ala-D-Ala and D-Ala-D-Ser dipeptides
      or the D Ala-D-Lac depsipeptide in an early step of peptidoglycan synthesis.
      Their function is essential for bacterial growth and specific to bacteria, making
      them attractive targets for the development of novel antibiotics. This review
      examines the biochemical and structural features of these enzymes and presents
      the main families of inhibitors described so far. Over the last 20 years, 7
      structures of DD-ligases have been solved by X-ray crystallography, giving a
      detailed view of the general topology of the active site and of the residues in
      the catalytic pocket that play a central role in substrate recognition. This has
      paved the way to the rational design of inhibitors, which can be classified as
      (i) analogues of substrates, (ii) analogues of the product of the reaction, (iii)
      analogues of the transition state, and (iv) original scaffolds discovered by
      screening or by rational computer-aided design. The three first strategies have
      led to molecules that are polar by nature and have therefore poor access to their
      cytosolic target. The fourth one is potentially most promising as it yields more
      diverse structures. The most active molecules show affinity constants in the
      microM range, but microbiological evaluation remains scarce (typical MIC 1-8 mg/L
      for the tested compounds). These data strongly suggest targeting DD-ligases is a
      promising approach for discovery of new antibiotics. Future research should,
      however, aim at finding more potent inhibitors endowed with the appropriate
      pharmacokinetic properties that ensure access to their intracellular target.

PMID- 19601799
TI  - Naturally occurring xanthones; latest investigations: isolation, structure
      elucidation and chemosystematic significance.
AB  - In this review, an updated literature survey covering the reports of naturally
      occurring xanthones in the period of 2005-2008 is presented. In some 143 studies,
      the isolation of 264 different xanthones from 36 plant species (representing 15
      genera in 6 families of higher plants), 7 species of fungi, and 1 lichen species
      were reported. Of these, 122 compounds were isolated for the first time from
      nature. We discuss plant origin, the way of separation, and spectral analysis
      done for structure elucidation, along with a brief discussion of the
      chemosystematic significance.

PMID- 19601800
TI  - p53-Induced apoptosis and inhibitors of p53.
AB  - Protein p53 is a key player in mitochondrial mediated apoptotic cell death and
      excess p53 activity has been implicated in many disease states such
      athrosclerosis, diabetes, osteoarthritis, Alzheimer's disease, Parkinson's
      disease, Huntington's disease, AIDS, P. falciparum and S. typhimurium infections.
      Thus, chemical inhibitors of p53 activation might prove effective in suppressing
      diseases associated with excess p53 activity. Diverse chemical compounds are
      being synthesized and evaluated as potent inhibitors of p53 in many cell types.
      In this review, we have focused on the effects of apoptosis, which is involved in
      p53 protein and inhibition of p53 induced apoptosis. Peculiar features of p53
      protein and its roles in various diseases are summarized along with important
      inhibitors developed in recent years.

PMID- 19601801
TI  - Lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in atherogenesis:
      a brief review.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger
      receptor that primarily binds and regulates oxidized low-density lipoprotein
      (LDL). Expression of LOX-1 is regulated by a feed-forward system stimulated by
      oxidized LDL (oxLDL), a major component of atherosclerosis. LOX-1 is a homodimer
      with a reactive backbone that can bind to a host of different ligands, including
      small molecules, and whole cells. LOX-1 is involved in many intercellular,
      intracellular, and molecular processes that are atherogenic. LOX-1 levels are
      elevated within atherosclerotic plaques and its expression is induced by
      proinflammatory cytokines. The ability of LOX-1 to bind many different ligands
      and control several atherogenic processes makes this receptor a likely vascular
      disease biomarker as well as an ideal choice for drug therapy aimed at preventing
      cardiovascular disease.

PMID- 19601802
TI  - The expression of endotoxic activity in the Limulus test as compared to cytokine
      production in immune cells.
AB  - Lipopolysaccharides (LPS, endotoxins) belong to the strongest elicitors of the
      mammalian immune system due to the induction of a series of cytokines such as
      tumor-necrosis-factor-alpha (TNFalpha) in immunocompetent cells like mononuclear
      cells. Since the effects of LPS on human health may be pathologically at too high
      concentrations (e.g., septic shock syndrome), it is of uttermost importance to
      have a reliable assay for measuring the concentrations of endotoxins in vitro and
      in vivo (human body fluids). The activation of the clotting cascade from the
      horseshoe crab (Limulus polyphemus), the Limulus amoebocyte lysate test (LAL),
      has been the standard and most sensitive assay to detect bacterial endotoxins.
      However, there are restrictions with this test. It was found in some clinical
      trials that the results from the LAL test did not correlate with the presence of
      bacteremia due to Gram-negative organisms or with the mortality but correlated
      with the presence of fungal bloodstream infections. This resulted from the fact
      that the LAL assay does not only respond to bacterial endotoxins but is activated
      also by (1-->3)-beta-D-glucan. Furthermore, in extensive studies the structural
      requirements for activation of the LAL test were analyzed, and it was found that
      the LAL activity correlated with pyrogenicity but not with activation of the
      complement cascade. Furthermore, there was no correlation of the LAL activity
      with cytokine expression (for example tumor-necrosis-factor-alpha and
      interleulkins-1 and 6) in mononuclear cells when the 4/2 acyl chain pattern of
      enterobacterial lipid A was changed, or when the cytokine production induced by
      LPS from various different species in the whole blood assay was compared with the
      response from the LAL test. To clarify the questions raised by the different
      experimental findings, data from literature are summarized to get a more closer
      insight where the Limulus test confidentially monitors the endotoxicity of LPS
      and other compounds and where this is not the case, and which are the decisive
      epitopes for recognition of the LPS molecules. These data are very crucial for
      example in clinical tests, whether the LAL assay can reliably describe the
      effectivity of an antibacterial therapy.

PMID- 19601803
TI  - Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and
      implications in drug development.
AB  - CYP2D6 accounts for only a small percentage of total hepatic CYPs (<2%), but it
      metabolizes approximately 25% of clinically used drugs (>100) with significant
      polymorphisms. A number of drugs acting on the central nervous system and
      cardiovascular system are substantially metabolized by CYP2D6. The enzyme also
      utilizes hydroxytryptamines and neurosteroids as endogenous substrates. In
      addition, CYP2D6 metabolizes procarcinogens and neurotoxins such as 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and
      indolealkylamines. Typical CYP2D6 substrates are usually lipophilic bases with a
      planar hydrophobic aromatic ring and a nitrogen atom which can be protonated at
      physiological pH, but several atypical substrates such as spirosulfonamide and
      pactimibe do not contain a basic nitrogen atom. The structure of human CYP2D6 has
      been recently determined and shows the characteristic CYP fold as observed in
      other members of the CYP superfamily, with a well-defined active site cavity
      above the heme group with a volume of approximately 540 A(3). CYP2D6 is largely
      uninducible by prototypical CYP inducers such as phenobarbital, rifampin and
      dexamethasone, but it is regulated by hepatocyte nuclear factor-4alpha, a nuclear
      receptor. CYP2D6 is subject to inhibition by a number of drugs and this may
      provide an explanation for numerous clinical drug interactions. CYP2D6 has an
      important role in drug development and it is a common practice for pharmaceutical
      industry nowadays to a great extent screen drug candidates early in development
      as possible CYP2D6 substrates and/or inhibitors and drop such candidates where
      they have alternatives. This candidate selection might eventually lead to a less
      prominent role of this enzyme in the future for drug metabolism and less
      interindividual variability in drug exposure and minimize potentially adverse
      drug interactions. Further studies are warranted to delineate the molecular
      mechanisms involved in the function and regulation of CYP2D6.

PMID- 19601804
TI  - The role of toll pathways in viral respiratory disease during early childhood.
AB  - Virus-induced respiratory disease accounts for the majority of hospitalizations
      of young children during the winter months. The major viral causes of lower
      respiratory tract disease in infants and children are respiratory syncytial virus
      (RSV), rhinovirus, metapneumovirus (hMPV), parainfluenza virus 3 (PIV-3), and
      influenza. The primary antiviral mechanism involves the activation of cytotoxic T
      cells and the clearance of virus-infected epithelial cells, and Toll-like
      receptors that recognize microbial molecular patterns are thought to initiate and
      orchestrate the immune response. Here, we review the role of Toll-like receptors
      in modulating the immune response to respiratory viral disease, including the
      role of maturation of the TLR system in early life.

PMID- 19601805
TI  - Heterotrimeric G proteins and apoptosis: intersecting signaling pathways leading
      to context dependent phenotypes.
AB  - Apoptosis, a programmed cell death mechanism, is a fundamental process during the
      normal development and somatic maintenance of all multicellular organisms and
      thus is highly conserved and tightly regulated through numerous signaling
      pathways. Apoptosis is of particular clinical importance as its dysregulation
      contributes significantly to numerous human diseases, primarily through changes
      in the expression and activation of key apoptotic regulators. Each of the four
      families of heterotrimeric G proteins (G(s), G(i/o), G(q/11) and G(12/13)) has
      been implicated in numerous cellular signaling processes, including
      proliferation, transformation, migration, differentiation, and apoptosis.
      Heterotrimeric G protein signaling is an important but not widely studied
      mechanism regulating apoptosis. G protein Signaling and Apoptosis broadly cover
      two large bodies of literature and share numerous signaling pathways. Examination
      of the intersection between these two areas is the focus of this review. Several
      studies have implicated signaling through each of the four heterotrimeric G
      protein families to regulate apoptosis within numerous disease contexts, but the
      mechanism(s) are not well defined. Each G protein family has been shown to
      stimulate and/or inhibit apoptosis in a context-dependent fashion through
      regulating numerous downstream effectors including the Bcl-2 family, NF-kappaB,
      PI3 Kinase, MAP Kinases, and small GTPases. These cell-type specific and G
      protein coupled receptor dependent effects have led to a complex body of
      literature of G protein regulation of apoptosis. Here, we review the literature
      and summarize apoptotic signaling through each of the four heterotrimeric G
      protein families (and the relevant G protein coupled receptors), and discuss
      limitations and future directions for research on regulating apoptosis through G
      protein coupled mechanisms. Continued investigation in this field is essential
      for the identification of important targets for pharmacological intervention in
      numerous diseases.

PMID- 19601807
TI  - Role of lipoxins and resolvins as anti-inflammatory and proresolving mediators in
      colon cancer.
AB  - Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense
      interest because of expanding views of their action, particularly in chronic
      disorders where unresolved inflammation is a key factor leading to colon
      carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic
      acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX
      2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation,
      peritonitis, dendritic cell migration, and interleukin production. This explains
      that dietary supplementation of omega-3 fatty acids generates potent local
      endogenous mediators that control inflammation. LXs are biosynthesized from COX
      2/LOX pathways. Metabolites of 15-LOX-1 and 2 are anti-tumorigenic; similarly, 15
      epi-LXA(4) synthesized during COX-2 acetylation by low doses of aspirin too
      possesses anti-tumorigenic effects. Acetylating nonsteroidal anti-inflammatory
      drugs (NSAIDs), like aspirin, switches COX-2 from forming PGE(2) (promoting
      tumorigenesis) to 15-epi-LXA(4) (antitumorigenesis). LXs and Rvs are endogenously
      generated during the spontaneous resolution phase. These newly identified LXs and
      Rvs have proved to be potent regulators of both leukocytes and cytokine
      productions, thereby regulating the events of interest in inflammation and
      resolution. In light of existing knowledge on interconnected pathways of pro
      inflammatory mediators (leukotrienes, chemokines (IL8, SDF-1 alpha, MIP-1 alpha,
      MCP-1,2 etc), and cytokines (IL3, IL6, IL12, IL-1 beta, GM-CSF, B94, TNF-alpha
      etc)), the anti-inflammatory properties of pro-resolving mediators in preventing
      chronic inflammation which leads to carcinogenesis needs further understanding.
      In this review, we explore the mechanisms that trigger formation of LXs and Rvs,
      to highlight the relative importance of LXs and Rvs in carcinogenesis in relation
      to pro-inflammatory mediators.

PMID- 19601806
TI  - Function and expression pattern of nonsyndromic deafness genes.
AB  - Hearing loss is the most common sensory disorder, present in 1 of every 500
      newborns. To date, 46 genes have been identified that cause nonsyndromic hearing
      loss, making it an extremely heterogeneous trait. This review provides a
      comprehensive overview of the inner ear function and expression pattern of these
      genes. In general, they are involved in hair bundle morphogenesis, form
      constituents of the extracellular matrix, play a role in cochlear ion homeostasis
      or serve as transcription factors. During the past few years, our knowledge of
      genes involved in hair bundle morphogenesis has increased substantially. We give
      an up-to-date overview of both the nonsyndromic and Usher syndrome genes involved
      in this process, highlighting proteins that interact to form macromolecular
      complexes. For every gene, we also summarize its expression pattern and impact on
      hearing at the functional level. Gene-specific cochlear expression is summarized
      in a unique table by structure/cell type and is illustrated on a cochlear cross
      section, which is available online via the Hereditary Hearing Loss Homepage. This
      review should provide auditory scientists the most relevant information for all
      identified nonsyndromic deafness genes.

PMID- 19601809
TI  - Genetic and molecular approaches to the immunopathogenesis of multiple sclerosis:
      an update.
AB  - Although the aetiology of MS remains elusive, several genetic approaches have
      provided clues to the underlying molecular pathogenesis. In addition to the well
      known association to HLA class II alleles, weak but highly significant
      association to the interleukin-7 receptor and interleukin-2 receptor genes has
      recently been established. A series of other promising candidate genes identified
      in large genome screens are under evaluation. The genetic predisposition to MS is
      so far shown to be mediated by common polymorphisms in genes encoding molecules
      involved in T cell activation and homeostasis, but only a small proportion of the
      potential susceptibility genes have yet been identified. Analyses of transcribed
      immune receptor genes have revealed evidence of antigen-driven clonal expansion
      of lymphocytes, and may also provide tools for charting their specificites.
      Recently, attempts to identify disease-associated genes through transcriptional
      profiling have revealed new candidate players in MS pathogenesis. Whereas genetic
      studies in humans may identify individual molecular players, transgenic animal
      models allow detailed examination of molecular pathways. These studies have shown
      that in addition to altered protein function, alteration of gene expression may
      contribute to disease development. We here review how different genetic
      approaches can be combined to elucidate the immuno-pathogenesis of MS.

PMID- 19601808
TI  - STAT3 regulation of glioblastoma pathogenesis.
AB  - Malignant gliomas are the most common primary brain tumors. Despite efforts to
      find effective treatments, these tumors remain incurable. The failure of
      malignant gliomas to respond to conventional cancer therapies may reflect the
      unique biology of these tumors, underscoring the need for new approaches in their
      investigation. Recently, progress has been made in characterization of the
      molecular pathogenesis of glioblastoma using a developmental neurobiological
      perspective, by exploring the role of signaling pathways that control the
      differentiation of neural stem cells along the glial lineage. The transcription
      factor STAT3, which has an established function in neural stem cell and astrocyte
      development, has been found to play dual tumor suppressive and oncogenic roles in
      glial malignancy depending on the mutational profile of the tumor. These findings
      establish a novel developmental paradigm in the study of glioblastoma
      pathogenesis and provide the rationale for patient-tailored therapy in the
      treatment of this devastating disease.

PMID- 19601810
TI  - Mouse models to decipher the PI3K signaling network in human cancer.
AB  - Deregulation of the PI3K pathway is common in human cancer. The basic players in
      this pathway are the kinases PI3K and AKT and the phosphatase PTEN. This review
      will summarize some of the key animal models that have helped us understand this
      signaling network and its contribution to tumorigenesis. Recently, great advances
      in cancer mouse models have been achieved [1]. While germline deletion often
      affects the development of the organism and can result in embryonic lethality,
      conditional knockout mouse models offer the possibility of inducing gene deletion
      in the adult organism. Another useful strategy involves the inactivation of
      enzyme function by introducing small mutations in the gene sequence, thereby
      maintaining the protein in an inactivated state and mimicking protein inhibition
      with drugs. Combining tissue-specific expression of PI3K and AKT with a secondary
      oncogenic event, for example, leads to the development of specific tumors. Such
      models are more accurate for growth studies of human tumors than those involving
      xenograft tumors, due to the interconnection of the tumors with blood vessels.
      These studies will improve the pharmacological analysis of drug candidates. With
      the discovery of oncogenic mutations in members of the PI3K pathway, mouse lines
      harboring these mutations are being developed in order to imitate the molecular
      features of a human tumor. Using these models for drug testing may enable more
      accurate prediction of the effects that a specific drug will have on a patient.

PMID- 19601811
TI  - STAT3 as a central regulator of tumor metastases.
AB  - Metastasis is a major cause of morbidity and mortality in patients with cancer.
      The molecular mechanisms that control metastasis are related to alterations in
      various oncogenes, tumor suppressor genes, metastasis suppressor genes, and
      growth factors and their receptors. These abnormalities affect the downstream
      signal transduction pathways involved in the control of cell growth and other
      malignant properties. One of the most recognized signal transduction pathways
      involves the signal transducer and activator of transcription 3 (STAT3) protein.
      STAT3, known to be activated by numerous cytokines, growth factors, and oncogenic
      proteins, is constitutively phosphorylated in several clinical cancer specimens
      and cell lines, leading to cell transformation and tumorigenesis. STAT3 target
      genes are involved in multiple steps of metastasis, including invasion, cell
      survival, self-renewal, angiogenesis, and tumor-cell immune evasion. Furthermore,
      the inhibition of STAT3 by a variety of mechanisms can exert anti-tumor and anti
      metastasis effects. These findings suggest that STAT3 might be an excellent
      target for therapeutic intervention in tumor metastases. This review highlights
      the pivotal role of STAT3 in tumor metastases and in therapeutic strategies to
      target the STAT3 signaling pathway for the inhibition of metastases.

PMID- 19601812
TI  - Developmental abnormalities and cancer predisposition in neurofibromatosis type
      1.
AB  - Neurofibromatosis type 1 (NF1) is a developmental and cancer predisposing
      syndrome resulting from haploinsufficiency or alteration in neurofibromin, a
      multifunctional protein that acts in various signaling pathways affecting
      morphogenetic processes and cell proliferation. Neurofibromin deficiency
      deregulates Ras/Raf/MEK/ERK and Ras/PI3K/AKT/PKB/mTOR signaling networks and
      intersected pathways including the cAMP-dependent protein kinase A (PKA) and the
      Rho-cofillin which acts on actin cytoskeleton reorganization, cell motility and
      adhesion. As the neurofibromin-mediated pathways are associated with biological
      effects depending on the cell lineage, deregulation induced by NF1 mutation
      clearly has cell type-specific effects. This review summarizes our increasing
      knowledge of NF1 as a disease rooted in defective developmental mechanisms that
      can also influence the potential for malignant growth. The cardinal features of
      NF1 patients, at birth and during life involve the cardiovascular,
      connective/skeletal and central nervous systems, as they reflect the NF1 mutation
      sensitivity of cell lineages committed to specifying these systems during
      embryonic development. A switch to neoplastic transformation may also occur in
      both the prenatal and postnatal life in cancer initiating cells of defined
      lineages, with the cooperation of a genetically and epigenetically modified tumor
      microenvironment. We emphasize how much of our current knowledge of the
      pathomechanisms of NF1 clinical signs and cancer has come from engineered mouse
      models and in vitro primary cells and cell lines exposed to inhibitors of
      signaling molecules. Advances in our knowledge of the developmental defects
      primed by the loss neurofibromin should reveal further associations between given
      NF1 mutations and tissue-specific symptoms, thus improving the clinical
      management of the patients.

PMID- 19601813
TI  - 17 AAG for HSP90 inhibition in cancer--from bench to bedside.
AB  - Heat shock protein 90 (HSP90) family of proteins are ubiquitous molecular
      chaperones that are involved in folding, activation, maturation and assembly of
      many proteins that include essential mediators of signal transduction and cell
      cycle progression. They are abundant in eukaryotic cells and localized to the
      cytoplasm, mitochondria as well as the endoplasmic reticulum under normal
      conditions, making up 1-2% of all cellular proteins. HSP90 proteins have
      increased expression in a number of malignancies. A large number of HSP90 client
      proteins have been shown to be necessary for the development, proliferation and
      survival of specific types of cancers. HSP90 inhibition can affect multiple
      oncogenic pathways and involved proteins, therefore make it an attractive target
      for drug development. This article serves as an overview of the pre-clinical data
      and clinical trial data on HSP90 inhibitor 17-AAG in different malignancies. 17
      AAG has shown significant anti-tumor activity against a spectrum of cancers in
      the pre-clinical studies and information from various phases of clinical trials
      is growing. The potential indication of 17-AGG for the treatment of refractory
      multiple myeloma now awaits for the results of two phase III studies. More work
      needs to be done before the broader oncological use of HSP90 inhibitors in the
      area of defining HSP90 client proteins, understanding the mechanism of HSP90
      actions, identifying reliable surrogate markers for HSP90 inhibition in vivo and
      optimizing drug delivery and efficacy.

PMID- 19601814
TI  - Treatment of multiple sclerosis.
AB  - Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system, with highly variable clinical course that most typically
      exhibits a relapsing-remitting pattern. Neuroimaging, pathological findings and
      response to available therapies are also not uniform. It commonly affects young
      adults and is usually characterized in the early years by acute relapses followed
      by partial or complete remission; in later years progressive and irreversible
      disability develops. The clinical course of MS is defined as relapsing-remitting
      (RRMS), primary progressive (PPMS), progressive relapsing (PRMS) and secondary
      progressive (SPMS). The treatment of RRMS is based on the use of
      immunosuppressive and immune-modulating therapy. Immunosuppressive agents have
      been used in multiple sclerosis for decades. Intravenous methylprednisolone is
      currently the treatment of choice for the relapses. The currently approved
      treatments for MS are disease-modifying agents, which only reduce the attack rate
      and delay progression in some patients and are believed to be effective only for
      the inflammatory component of the disease. Immunomodulating and immunosuppressive
      treatments are directed against the inflammatory process and are only partially
      effective. In RRMS, positive effects on disease activity have slowed disability
      progression, but in PPMS the same degree of effect of immunotherapies on relapses
      and active MRI lesions had little or no effects on the progression of disability.
      This partial failure could be explained by mechanisms of axonal damage at least
      partially independent from acute or chronic inflammation. This suggests that
      there is a need for better use of available treatments and the necessity of
      alternative new therapeutic options to stop disease progression and improve
      recovery mechanisms. The practicing neurologist must understand the MS spectrum
      and evaluate patient-specific factors to determine the best strategy for therapy.

PMID- 19601815
TI  - Neuromodulators and therapeutic targets in neuropathic pain: from molecules to
      man.
AB  - Neuropathic pain is a phenomenon characterized by a high population prevalence by
      possessing several etiologies. In contrast to nociceptive pain, painful signals
      in neuropathic pain are originated in the nervous system, present poor responses
      to conventional treatments and may worsen the quality of life. Antiepileptic
      drugs are increasingly used for different purposes including migraine,
      neuropathic pain, tremor or psychiatric disorders and they have started to be
      called neuromodulators. These drugs may act on very different targets such as
      sodium, potassium or calcium channels, purinergic, GABAergic, glutamatergic or
      vanilloid receptors and different cytokines including IL-6 or TNF, each if which
      may be important in managing some aspects of neuropathic pain. Antiepileptic
      drugs have demonstrated effectiveness in the treatment of this pathology, and
      owing to the important development of these drugs in the last years, they may
      become a very effective tool. On the other hand, the increasing knowledge of the
      pathophysiology of nociception is leading to new channels and receptors as
      potential targets for treatment. In this paper we try to review the different
      potential therapeutic targets and role of antiepileptic drugs in the treatment of
      this pathology.

PMID- 19601816
TI  - Antiangiogenic therapy for high-grade gliomas.
AB  - BACKGROUND: Gliomas and in particular high-grade gliomas (HGG) demonstrate when
      compared to other non-neural solid cancers amongst the highest levels of tumor
      angiogenesis (the formation of new blood vessels from pre-existing vasculature).
      METHODS: Angiogenesis is a common theme in cancer biology and reflects the
      requirement of a vascular network to support continued uncontrolled cancer
      growth. Early recognition of this paradigm suggested a potential and novel cancer
      treatment target that led to the discovery and implementation of antiangiogenic
      therapies. Two basic strategies of cancer antiangiogenic therapy have emerged,
      one targeting vascular endothelial growth factor, VEGF (growth factor ligand
      based antagonists) and the second targeting the vascular endothelial growth
      factor receptor, VEGFR (receptor-based antagonists, small molecule tyrosine
      kinase inhibitors). Emerging literature suggests efficacy of antiangiogenic
      therapy for recurrent HGG. RESULTS: Notwithstanding the limited literature
      regarding the treatment of recurrent HGG with antiangiogenic therapy
      (predominantly ligand-based and administered in conjunction with cytotoxic
      chemotherapy), this therapy has become the de facto standard of care for many.
      Response rates vary from 30-60% and 6-month progression free survival varies from
      25-50%. Problematic however are new antiangiogenic class side effects
      (hypertension, fatigue, proteinuria, intratumoral hemorrhage, arterial thrombosis
      and wound dehiscence), timing in relationship to surgery, measurements of
      response, lack of established dose response relationships and pharmacoeconomics
      and a possible change in tumor biology. CONCLUSIONS: Ligand-based antiangiogenic
      therapy (in particular bevacizumab) is a compelling new targeted therapy for HGG
      and will continue to emerge as an important novel anti-glioma therapy. Further
      studies are required to define the population of patients with HGG in whom this
      therapy is of benefit, identify the optimal dose and schedule, better
      characterize the value of co-administered (cytotoxic and targeted) therapies and
      establish validated response measures.

PMID- 19601817
TI  - Blood-brain barrier transport of drugs for the treatment of brain diseases.
AB  - The central nervous system is a sanctuary protected by barriers that regulate
      brain homeostasis and control the transport of endogenous compounds into the
      brain. The blood-brain barrier, formed by endothelial cells of the brain
      capillaries, restricts access to brain cells allowing entry only to amino acids,
      glucose and hormones needed for normal brain cell function and metabolism. This
      very tight regulation of brain cell access is essential for the survival of
      neurons which do not have a significant capacity to regenerate, but also prevents
      therapeutic compounds, small and large, from reaching the brain. As a result,
      various strategies are being developed to enhance access of drugs to the brain
      parenchyma at therapeutically meaningful concentrations to effectively manage
      disease.

PMID- 19601818
TI  - Polymer-based drug delivery devices for neurological disorders.
AB  - Polymer based therapies offer many potential advantages in the treatment of
      diseases of the nervous system, and would allow delivery of therapeutic agents
      directly to the relevant area of brain, circumventing obstacles presented by the
      blood brain barrier, avoiding the side-effects often associated with systemic
      medication administration, and permitting much smaller doses of medication. As
      improvements in diagnostic procedures, particularly imaging, now provide very
      accurate localization of therapeutic targets in many of these conditions, it is
      technically feasible to deliver such agents precisely to the relevant brain
      region. Combined with advances in polymer sciences, there is renewed interest in
      focal drug delivery systems, particularly around intelligent or controlled
      release systems which would extend the life-span of these devices considerably.
      Major obstacles remain, however, particularly around the safety and
      biocompatibility of such materials, and the complexity of testing in clinical
      scenarios. We review here the current status of animal and human studies in this
      rapidly evolving area, addressing some of the practical obstacles and examining
      the range of potential applications in chronic neurological disease.

PMID- 19601819
TI  - Neuroprotective effects of tetracyclines: molecular targets, animal models and
      human disease.
AB  - Tetracyclines are a class of antibiotics which could play a therapeutic role in
      several neurological disorders. Minocycline, extensively studied in animal
      models, decreased the size of ischaemic and haemorrhagic infarct. In Parkinson's
      disease models minocycline protected the nigrostriatal pathway, and in
      Huntington's disease and motoneuron disease models delayed the progression of
      disease extending the lifespan. Finally, in human diseases such as stroke and
      multiple sclerosis tetracyclines seem to play some neuroprotective role. The main
      biological effects of tetracyclines are the inhibition of microglial activation,
      the attenuation of apoptosis, and the suppression of reactive oxygen species
      production. These mechanisms are involved in the pathogenesis of several
      neurodegenerative disorders. Several reports showed that minocycline reduced
      mitochondrial Ca(2+) uptake, stabilized mitochondrial membranes, and reduced the
      release into the cytoplasm of apoptotic factors. Other effects include up
      regulation of mitochondrial bcl-2 (an antiapoptotic protein), direct scavenging
      of reactive oxygen species, and inhibition of mitogen activated protein kinases.
      It is still unclear which of these mechanisms plays the pivotal role in
      neuroprotective properties of tetracyclines. The anti-apoptotic effect of
      tetracyclines probably involves the mitochondrion. The major target for
      tetracyclines in neurodegeneration could lie within the complex network that
      links mitochondria, oxidative stress, poly (ADP-ribose) polymerase-1 and
      apoptosis. Here, we review the neuroprotective effects of tetracyclines in animal
      models and in human disease, and we focus on their possible mechanism(s) of
      action, with special regard to mitochondrial dysfunction in neurodegeneration.

PMID- 19601820
TI  - Perspectives of pharmacokinetics and metabolism in drug design.

PMID- 19601821
TI  - Drug metabolism and pharmacokinetics in support of drug design.
AB  - Pharmacokinetics has been recognized as one of the elements determining the
      probability of success in pharmaceutical research. As a result, compounds are
      routinely evaluated in drug discovery for their absorption, distribution,
      metabolism and elimination properties. The primary objective of these studies is
      to eliminate "flawed" molecules or a structural class based on preset selection
      criteria, while building a knowledge base for compilation of structure-activity
      relationships to guide chemistry synthesis efforts. This article is intended to
      provide a brief overview combined with critical evaluation on several strategies
      employed during lead optimization processes, and the analyses are supported by
      case studies. Future directions are discussed in the context of overcoming
      deficiencies in the current practice by developing tools enabling better
      prediction of clinical outcomes.

PMID- 19601822
TI  - Drug-like property concepts in pharmaceutical design.
AB  - The pharmaceutical industry is facing an ever increasing challenge to deliver
      safer and more effective medicines. Traditionally, drug discovery programs were
      driven solely by potency, regardless of the properties. As a result, the
      development of non-drug-like molecules was costly, had high risk and low success
      rate. To meet the challenges, the bar has been rising higher for drug candidates.
      They not only need to be active, but also drug-like to be advanced to clinical
      development. Drug-like properties, such as solubility, permeability, metabolic
      stability and transporter effects are of critical importance for the success of
      drug candidates. They affect oral bioavailability, metabolism, clearance,
      toxicity, as well as in vitro pharmacology. Insoluble and impermeable compounds
      can result in erroneous biological data and unreliable SAR in enzyme and cell
      based assays. Rapid metabolism by enzymes and high efflux by transporters can
      lead to high clearance, short half-life, low systemic exposure and inadequate
      efficacy. Early property information helps teams make informed decisions and
      avoids wasting precious resources. Structure-property relationships are essential
      to guide structural modification to improve properties. High throughput ADME/TOX
      assays have been implemented and are being widely used to drive drug discovery
      projects in parallel with activity screening. Property design has become an
      integrated and inseparable part of the modern drug discovery paradigm. The
      approach has been proven to be a winning strategy.

PMID- 19601823
TI  - Comprehensive assessment of ADMET risks in drug discovery.
AB  - The high attrition rate in drug development and the deteriorated drug ability as
      a result of the shifted chemical space of new therapeutic target for unmet
      medical needs have posed drastic challenges in current drug discovery. It has
      triggered the strategic transition in the past decade into parallel assessment of
      efficacy and comprehensive ADMET (absorption, distribution, metabolism,
      elimination and toxicity) properties of new chemical entities (NCEs) in the lead
      selection and optimization stages, to convert chemically a problematic NCE to an
      "all-around" candidate. This review summarizes multiple in silico, in vitro and
      in vivo ADMET filters developed and implemented in various stages of drug
      discovery to flag potential ADMET issues in the clinic. The full awareness of the
      benefits and limitations of each tool assures right questions to be answered
      using right tools at right time. The integrated ADMET risk assessment will allow
      project teams to have a clear vision in terms of the competitive position of own
      NCEs against comparable marketed drugs.

PMID- 19601824
TI  - Metabolite identification and profiling in drug design: current practice and
      future directions.
AB  - Drug metabolism and pharmacokinetics (DMPK) represents a critical component in
      support of drug discovery and development. This is because the therapeutic
      efficacy of a drug is dependent on its exposure which in turn is dictated in part
      by metabolic stability of the molecule. In addition, drug metabolism may lead to
      the formation of metabolites that can either be pharmacologically active or
      elicit adverse effect. On this basis, metabolite identification and profiling
      have become a routine exercise during lead optimization and subsequent
      development processes. The current communication provides an overview on the
      account of metabolite identification and profiling in support of drug design with
      an additional emphasis on the commonly used analytical techniques. The discussion
      is supported by case studies. Future directions are discussed in the context of
      newer platforms of technology and bioanalytical approaches enabling better
      operation efficiency in pharmaceutical research.

PMID- 19601825
TI  - Current prodrug design for drug discovery.
AB  - Prodrugs are inactive compounds which are metabolized either chemically or
      enzymatically in a controlled or predictable manner to the parent active drug
      inside the body. Prodrugs can enhance the therapeutic efficacy and/or reduce
      adverse effects via different mechanisms, including increased solubility,
      improved permeability and bioavailability, prolonged half-life, and tissue
      targeted delivery. Besides the prodrug itself, optimization of vehicles and other
      enhancement techniques is important as well. Strategies to improve the oral
      bioavailability and achieve tumor-specific targeting have been the most important
      developments in prodrug design during the last 5 years. This review describes
      recent developments in orally administered and tumor-targeted prodrugs.
      Pharmacokinetic and pharmacodynamic evaluations of these prodrugs are
      systematically introduced in this review.

PMID- 19601826
TI  - The role of hyphenated chromatography-mass spectrometry techniques in exploratory
      drug metabolism and pharmacokinetics.
AB  - The advances in high-speed synthesis technologies have produced a large number of
      biologically active new chemical entities (NCEs) for developability assessment.
      Current drug discovery efforts have been focused on identifying drug metabolism
      and pharmacokinetic (DMPK) issues at the earliest possible stage in order to
      reduce the attrition rate of drug candidates during the development phase. Mass
      spectrometry (MS) has proven a powerful tool in providing rapid qualitative and
      quantitative measurements of drug molecules for DMPK studies in both drug
      discovery and development. Although mass spectrometers can serve as separation
      devices, for most pharmaceutical applications, some form of chromatography is
      combined with MS. For most MS-based methods, tandem mass spectrometry (MS/MS)
      utilizes atmospheric pressure ionization (API) and chromatographic techniques.
      This review describes the major hyphenated chromatography-mass spectrometry
      techniques and their applications in supporting exploratory DMPK studies
      including various in vitro and in vivo PK and metabolite identification profiles.

PMID- 19601827
TI  - The role of exploratory drug metabolism and pharmacokinetics in new drug
      research: case study-selection of a thrombin receptor antagonist for development.
AB  - The rising costs and time associated with bringing new medicines to the market
      have created a need for a new paradigm for reducing the attrition rates of drug
      candidates in both preclinical and clinical development stages. Early appraisal
      of drug metabolism and pharmacokinetic (DMPK) parameters is now possible due to
      several higher throughput in vitro and in vivo screens. This knowledge of DMPK
      properties should not only shorten the timelines for the selection of drug
      candidates but also enhance the probability of their success for development. The
      role of DMPK researchers in the drug research paradigm should not be limited to
      screening a large array of compounds during the lead optimization process but
      should include a strive for an understanding of the absorption, distribution,
      metabolism, excretion, and potential drug-related toxicities of a chemical
      series. As an example, in this article we present a specific DMPK research
      screening paradigm and describe a case study using the Thrombin Receptor
      Antagonist program. This screening paradigm followed by the extensive lead
      optimization process culminated in the selection of SCH 530348, a potent,
      selective and orally active thrombin receptor antagonist for the treatment of
      thrombosis.

PMID- 19601828
TI  - ADAMs: targets for drug discovery.

PMID- 19601829
TI  - ADAM8/MS2/CD156, an emerging drug target in the treatment of inflammatory and
      invasive pathologies.
AB  - While it is highly accepted that ADAM family members with ubiquitous expression
      patterns, such as ADAM10 and ADAM17 have major roles in homoeostasis and
      pathology, ADAM8 was initially considered as an immune-specific ADAM with a cell
      specific expression pattern. Therefore, ADAM8 had a "sleeping beauty" existence
      for many years, and has recently come back into focus as it was detected under
      several pathological conditions. These were found to typically involve
      inflammation and remodelling of the extracellular matrix, including cancers and
      serious respiratory diseases such as asthma. In these diseases, induced
      expression of ADAM8 by different stimuli results in cleavage of various
      substrates, including cell adhesion molecules, cytokine receptors, and ECM
      components. Involvement of ADAM8 in individual diseases indicates its usefulness
      as both a diagnostic and prognostic marker. Even more strikingly, as ADAM8
      progressively emerges as a key effector in pathological processes, so does its
      attractiveness as a therapeutic target rather than being a mere indicator of
      disease and its progression. This is encouraged by analysis of ADAM8 null mice,
      identifying no adverse phenotype in the absence of functional ADAM8. Thus, ADAM8
      potentially is an attractive drug target in a variety of diseases. In this
      review, the current knowledge on ADAM8 in diseases and avenues for specific
      inhibition based on unique biochemical features of ADAM8 will be presented.

PMID- 19601830
TI  - ADAM9 as a potential target molecule in cancer.
AB  - ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in
      the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged
      as critical regulators of cell-cell signaling during development and homeostasis,
      and are believed to contribute to pathologies, such as cancer, where their
      regulation is altered. ADAM9 is consistently overexpressed in various human
      cancers, and plays a role in tumorigenesis in mouse models. ADAM9 cleaves and
      releases a number of molecules with important roles in tumorigenesis and
      angiogenesis, such as EGF, FGFR2iiib, Tie-2, Flk-1, EphB4, CD40, VCAM-1, and VE
      cadherin, and could represent a potential therapeutic target in tumors where it
      is highly expressed. This review provides an overview of ADAM9 with a major focus
      on its contribution to tumorigenesis. Its role in the shedding of cell surface
      molecules will be discussed along with emerging aspects of regulation and
      possible functions in cancer development.

PMID- 19601831
TI  - ADAM10 as a therapeutic target for cancer and inflammation.
AB  - Both cancer and chronic inflammatory diseases are often marked by homeostatic
      signal transduction pathways run amok. Cleavage of membrane-bound substrates by
      extracellular metalloproteinases is frequently the rate limiting step in
      activating many of these pathways, resulting either in liberation of active
      ligands (shedding) or initiating further processing into bioactive cytoplasmic
      domains (regulated intramembrane proteolysis or RIP). ADAM10 is a member of the
      ADAM (A Disintegrin And Metalloproteinase) family of transmembrane
      metalloproteinases implicated in the RIPing and shedding of dozens of substrates
      that drive cancer progression and inflammatory disease, including Notch, E
      cadherin, EGF, ErbB2 and inflammatory cytokines. ADAM10's emerging role as a
      significant contributor to these pathologies has led to intense interest in it as
      a potential drug target for disease treatment. Here we discuss some of the
      established functions of ADAM10 and the implications of its inhibition in disease
      progression.

PMID- 19601832
TI  - Targeting ADAM12 in human disease: head, body or tail?
AB  - ADAM12/meltrin alpha is a type I transmembrane multidomain protein involved in
      tumor progression and other severe diseases, including osteoarthritis, and as
      such could be considered as a potential drug target. In addition to protease
      activity, ADAM12 possesses cell binding and cell signaling properties. This
      functional trinity is reflected in the structure of ADAM12, which can be divided
      into head, body, and tail. The head of the protein (consisting of the pro and
      catalytic domains) mediates processing of growth factors and cytokines and has
      been implicated in epidermal growth factor (EGF) and insulin-like growth factor
      receptor signaling. The body of the protein (consisting of the disintegrin,
      cysteine-rich, and EGF-like domains) is involved in contacts with the
      extracellular matrix and other cells through interactions with integrins and
      syndecans. Finally, the tail of the protein (consisting of the cytoplasmic
      domain) is engaged in interactions with intracellular signaling molecules. In
      many studies, ADAM12 overexpression has been correlated with disease, and ADAM12
      has been shown to promote tumor growth and progression in cancer. On the other
      hand, protective effects of ADAM12 in disease have also been reported. Future
      investigations should address the precise mechanisms of ADAM12 in disease and
      biology in order to counterbalance the benefits from targeting ADAM12
      therapeutically with possible side effects. This review describes the biology of
      ADAM12, its association with disease, and evaluates the possible approaches to
      targeting ADAM12 in human disease.

PMID- 19601833
TI  - The therapeutic potential of ADAM15.
AB  - ADAM15 is a widely expressed multi-domain protease that has been implicated in
      the pathogenesis of many human diseases. Given the diversity of the ADAM15
      functional domains, this protease is thought to affect several important cellular
      processes, including cell adhesion, degradation of extracellular matrix
      components, and ectodomain shedding of membrane-bound growth factors that are
      intrinsic to cancer and various inflammatory conditions. The multiple levels by
      which the activity of ADAM15 can be regulated include signal transduction,
      modulation of catalytic function, spatial regulation, and post-translational
      modifications. Taken together, this multi-functional disintegrin protease not
      only offers a variety of potential targets for therapeutic intervention, but also
      represents an attractive target for pharmaceutical consideration due to its
      involvement in key cellular processes and various disease states. Modalities
      aimed at inhibiting protease activation, metalloproteinase activity, or integrin
      binding capability could prove beneficial for the treatment of cancer and
      inflammatory diseases.

PMID- 19601834
TI  - ADAM17 as a therapeutic target in multiple diseases.
AB  - As a metalloproteinase specialized in releasing membrane-tethered proteins, A
      Disintegrin and A Metalloproteinase 17 (ADAM17), also known as Tumor necrosis
      factor-alpha Converting Enzyme (TACE) or less commonly CD156q, has received more
      than its share of attention. This is mainly because major contemporary
      pathologies like cancer, inflammatory and vascular diseases seem to be connected
      to its cleavage abilities. The involvement in such a broad spectrum of diseases
      is due to the large variety of substrates that ADAM17 is able to cut. ADAM17 can
      activate growth factors or inactivate receptors by shedding their extracellular
      domain from the cell membrane. Similarly, it can detach cells by cleaving cell
      adhesion molecules. Some of these proteolytic events are part of cleavage
      cascades known as Regulated Intramembrane Proteolysis and lead to intracellular
      signaling. It is therefore clear that ADAM17 literally fulfills a key role in
      diverse processes and pathologies, making it a prime target for developing
      therapies. Here we review the role of ADAM17 in health and disease and highlight
      the problems to overcome for ADAM17 to mature towards a therapeutically valuable
      target.

PMID- 19601835
TI  - ADAM19/adamalysin 19 structure, function, and role as a putative target in tumors
      and inflammatory diseases.
AB  - A disintegrin and metalloproteinase 19 (ADAM19, or adamalysin 19) is a cell
      surface glycoprotein with a signal sequence, a prodomain, a metalloproteinase
      domain, a disintegrin domain, a cysteine-rich domain, a epidermal growth factor
      like domain, a transmembrane domain, and a cytoplasmic domain. It is an
      endopeptidase that cleaves extracellular matrix proteins and sheds growth factors
      and cytokines such as neuregulins, heparin-binding epidermal growth factor, tumor
      necrosis factor (TNF)-alpha, and TNF-related activation-induced cytokine. The
      ADAM19 gene was cloned from human, monkey, and mouse. It is expressed in multiple
      organs and tissues including heart, lung, bones, brain, spleen, liver, skeletal
      muscle, kidney, and testes. ADAM19 plays essential roles in embryo implantation,
      cardiovascular morphogenesis, neurogenesis, and other developmental processes. It
      has constitutive alpha-secretase activity associated with processing Alzheimer's
      disease amyloid precursor protein (APP) to non-amyloidogenic fragments; thus, it
      is neuroprotective. Those observations indicate that inhibition of ADAM19
      activity is undesirable during embryo development and morphogenesis, and during
      the development of Alzheimer's disease. On the contrary, in adults, ADAM19 is
      upregulated in human brain tumors such as astrocytoma and glioblastoma and is
      correlated with the invasiveness of glioma. It is also over-expressed by many
      human cancerous cell lines including cancers of the colon, ovary, lung, and
      brain. Abnormally high expression of ADAM19 is also linked to inflammation and
      fibrosis of the lung and kidney. Targeted inhibition of ADAM19 may be crucial for
      the treatment of certain types of tumors and inflammatory diseases.

PMID- 19601836
TI  - ADAM28 as a target for human cancers.
AB  - ADAM28 is a member of the ADAM (a disintegrin and metalloproteinase) gene family
      and consists of two isoforms, prototype membrane-type form and short secreted
      form. The metalloproteinase domain of ADAM28 has the zinc-binding consensus
      sequence, and ADAM28 exhibits catalytic activity to a few substrates such as
      insulin-like growth factor binding protein-3. The disintegrin domain interacts
      with integrins alpha4beta1, alpha4beta7 and alpha9beta1. In human non-small cell
      lung carcinomas and breast carcinomas, ADAM28 is overexpressed predominantly by
      carcinoma cells, and the expression correlates with carcinoma cell proliferation
      and lymph node metastasis. In this review we present our data on the activation
      of proADAM28, the tissue localization in human cancers and the interaction
      molecules, and discuss the regulation of ADAM28 activity and gene expression, the
      functions of ADAM28 in human cancers and the possibility of ADAM28 as a target
      for cancers.

PMID- 19601837
TI  - A review of the ADAMTS family, pharmaceutical targets of the future.
AB  - The disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family
      of metalloproteases consists of 19 members. These enzymes play an important role
      in the turnover of extracellular matrix proteins in various tissues and their
      altered regulation has been implicated in diseases such as cancer, arthritis and
      atherosclerosis. Unlike other metalloproteinases, ADAMTS members demonstrate a
      narrow substrate specificity due to the various exosites located in the C
      terminal regions of the enzymes, which influence protein recognition and matrix
      localization. The tight substrate specificity exhibited by ADAMTS enzymes makes
      them potentially safe pharmaceutical targets, as selective inhibitors designed
      for each member will result in the inhibition or cleavage of only a limited
      number of proteins. With the recent elucidation of crystal structures for ADAMTS
      1, -4 and -5, the design of potent and selective small molecule inhibitors is
      underway and will lead to drug candidates for evaluation in clinical trials in
      the next 5-10 years.

PMID- 19601839
TI  - Multifunctional antimicrobial proteins and peptides: natural activators of immune
      systems.
AB  - In addition to the physical barrier of the stratum corneum, cutaneous innate
      immunity also includes the release of various humoral mediators, such as
      cytokines and chemokines, recruitment and activation of phagocytes, and the
      production of antimicrobial proteins/peptides (AMPs). AMPs form an innate
      epithelial chemical shield, which provides a front-line component in innate
      immunity to inhibit microbial invasion; however, this might be an
      oversimplification of the diverse functions of these molecules. In fact, apart
      from exhibiting a broad spectrum of microbicidal properties, it is increasingly
      evident that AMPs display additional activities that are related to the
      stimulation and modulation of the cutaneous immune system. These diverse
      functions include chemoattraction and activation of immune and/or inflammatory
      cells, the production and release of cytokines and chemokines, acceleration of
      angiogenesis, promotion of wound healing, neutralization of harmful microbial
      products, and bridging of both innate and adaptive immunity. Thus, better
      understanding of the functions of AMPs in skin and identification of their
      signaling mechanisms may offer new strategies for the development of potential
      therapeutics for the treatment of infection- and/or inflammation-related skin
      diseases. Here, we briefly outline the structure, regulation of expression, and
      multifunctional roles of principal skin-derived AMPs.

PMID- 19601840
TI  - Peptides targeting angiogenesis related growth factor receptors.
AB  - Growth factors (GFs) are extracellular signaling polypeptides regulating cell
      proliferation, differentiation and survival. They exert a wide spectrum of
      biological activities selectively binding to and activating specific membrane
      receptors which then transfer the message to cell interior inducing specific
      biochemical pathways. GFs are especially involved in the regulation of
      angiogenesis, a physiological process underlining several pathologies. Molecules
      able to modulate angiogenesis, interfering with the molecular recognition between
      a GF and its receptor, have a big pharmacologic interest. Either GF and the
      receptor are potential drug target. Peptides are useful molecules to develop new
      lead compounds disrupting protein-protein interface for pharmacological
      applications. In this review we describe peptides targeting the receptors of the
      pro-angiogenic growth factors FGF, PDGF and VEGF. The biological function and the
      structure of each growth factor/receptor system are discussed, as well as the
      molecular interaction between peptides and the receptors. Finally, we highlight
      the pharmacological and diagnostic applications of these peptides in angiogenesis
      related diseases.

PMID- 19601841
TI  - Naturally occurring and synthetic peptides acting on nicotinic acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane-bound proteins
      belonging to the large family of ligand-gated ion channels. nAChRs possess
      various binding sites which interact with compounds of different chemical nature,
      including peptides. Historically first peptides found to act on nAChR were
      synthetic fragments of snake alpha-neurotoxins, competitive receptor antagonists.
      Later it was shown that fragments of glycoprotein from rabies virus, having
      homology to alpha-neurotoxins, and polypeptide neurotoxins waglerins from the
      venom of Wagler's pit viper Trimeresurus (Tropidolaemus) wagleri bind in a
      similar way, waglerins being efficient blockers of muscle-type nAChRs.
      Neuropeptide substance P appears to interact with the channel moiety of nAChR.
      beta-Amyloid, a peptide forming senile plaques in Alzheimer's disease, also can
      bind to nAChR, although the mode of binding is still unclear. However, the most
      well-studied peptides interacting with the ligand-binding sites of nAChRs are so
      called alpha-conotoxins, peptide neurotoxins from marine snails of Conus genus.
      First alpha-conotoxins were discovered in the late 1970s, and now it is a rapidly
      growing family due to isolation of peptides from multiple Conus species, as well
      as to cloning, and chemical synthesis of new analogues. Because of their unique
      selectivity towards distinct nAChR subtypes, alpha-conotoxins became valuable
      tools in nAChR research. Recent X-ray structures of alpha-conotoxin complexes
      with acetylcholine-binding protein, a model of nAChR ligand-binding domains,
      revealed the details of the nAChR ligand-binding sites and provided the basis for
      design of novel ligands.

PMID- 19601843
TI  - Peptide inhibitors targeting protein kinases.
AB  - Phosphorylation by protein kinases is a central theme in biological systems.
      Aberrant protein kinase activity has been implicated in a variety of human
      diseases, therefore, modulation of kinase activity represents an attractive
      therapeutic approach for the treatment of human illnesses. Development and design
      of specific inhibitors for protein kinases thus became a major strategy in many
      drug discovery programs. Inhibition of protein kinase activity may be achieved by
      blocking the phosphorylation activity or by disrupting protein-protein
      interactions. Peptides that can mimic most truly these regulatory modes are
      favorite choice for protein kinase-targeting. Here we focus on important motifs
      regulating the protein kinase signaling network and described how they may be
      exploited for peptide drug design. Protein kinases are important regulators of
      most, if not all, biological processes. Their abnormal activity has been
      implicated as causal factors in many human diseases, including cancer, diabetes
      and neurodegenerative disorders [1-3]. Protein kinases are thus attractive
      targets for drug design and compounds that manipulate their cellular activity are
      of enormous therapeutic potential. With a target in hand, medicinal chemists can
      generate low molecular weight compounds that bind the target with high affinity
      and alter its biological behavior. In many cases, however, drugs fail as they
      lack appropriate pharmaceutical properties and are of limited specificity
      resulting in unfavorable side effects. Under these circumstances, the use of
      peptides, which copy 'natural' motifs that specifically influence kinase activity
      and/or its intracellular interactions with cognate partners, may be a promising
      approach for selective inhibition of protein kinases. In this review we focus on
      the strategies to design such peptide inhibitors, focusing mainly on the
      serine/threonine protein kinase family.

PMID- 19601842
TI  - Current status and perspectives in peptide receptor radiation therapy.
AB  - Regulatory peptide receptors are overexpressed in numerous human cancers. The
      specific receptor binding property of peptides can be exploited by their
      labelling with a radionuclide and their use as carriers to guide the
      radioactivity to the tissues expressing their specific receptors. During the past
      decade, radiolabelled receptor-binding peptides have emerged as an important
      class of radiopharmaceuticals for tumour diagnosis and therapy. The first and
      most successful imaging agents to date are somatostatin analogues which are
      routinely used for somatostatin receptor scintigraphy. Peptide receptor
      radionuclide therapy (PRRT) with (90)Y-DOTA-octreotide and (177)Lu-DOTA
      octreotate in neuroendocrine tumours (NETs) results in symptomatic improvement,
      prolonged survival, and enhanced quality of life. The results in terms of tumour
      regression are very encouraging with few and mostly mild side effects when
      patients are carefully selected and kidney protective agents are given.
      Nevertheless much profit can be gained from improving the available receptor
      targeting strategies and developing new strategies. In this review, the current
      state of clinical use of radiolabelled peptides for diagnosis and therapy of NETs
      is presented. In addition, potential directions for optimization and future
      developments are discussed. These include the optimization of peptide analogues
      or derivatives, increasing the access and binding on specific receptors on the
      tumour sites, increasing radiotoxicity profile and multimodality strategies.
      Other peptides such as minigastrin, glucagon-like peptide-1 (GLP-1),
      cholecystokinin (CCK), bombesin (BN)/gastrin-releasing peptide (GRP), substance
      P, neurotensin (NT), neuropeptide Y (NPY) and RGD peptides are promising for PRRT
      and currently under preclinical and clinical development.

PMID- 19601844
TI  - Peptides as signaling inhibitors for mammalian MAP kinase cascades.
AB  - Mammalian MAPK cascades are essential for cellular signaling in response to
      mitogenic signals and stress-stimuli to regulate proliferation, differentiation
      and apoptosis. The three major MAPK cascades, ERK1/2-, JNK- and p38, maintain
      signaling specificity by scaffolding proteins and by specific docking
      interactions between pathway components. The structures mediating these
      interactions include the domain of versatile docking (DVD) responsible for MAP3K
      MAP2K-interaction and the common docking (CD)-domain and the ED
      (glutamate/aspartate)-site of MAPKs together with the various docking (D) motifs
      in MAP2Ks, MAPK substrates and MAPK-phosphatases. Several of these interactions
      have been studied in great detail. First approaches to use this knowledge to
      develop peptides that specifically inhibit MAPK signaling in disease models have
      been reported. It becomes obvious that specificity of peptides competing with
      kinase-docking is comparable to or even superior to small molecule ATP
      competitive inhibitors. In addition to specifically targeting protein-protein
      interactions, the ultimate efficacy of these peptide inhibitors in vivo also
      depends on their delivery, stability and toxicity in living cells and in the
      whole organism.

PMID- 19601845
TI  - Targeting rho GTPases by peptidic structures.
AB  - Rho GTPases represent a family of small GTP-binding proteins that are involved in
      many important cellular functions relevant to cancer including cell cytoskeleton
      organization, migration, transcription, and proliferation. Since deregulation of
      members of Rho GTPase family is often found associated with many disease states,
      targeting of Rho GTPases and related signaling pathways for potential therapeutic
      benefits has been extensively pursued. Recent progress in this field of studies
      by peptide and peptidomemic inhibitors has provided important validations to this
      principle. The possibility to design and synthesize specific peptides that can
      bind to specific surface of the targeting proteins to elicit transient and
      specific blockade of the signal flows that require defined protein-protein
      interactions makes peptide inhibitors an attractive approach. In this review we
      summarize the recent advances in the design and application of a number of
      polypeptide and peptidomimetic structures that specifically target individual
      members of Rho GTPases and their up- or down-stream signaling
      regulators/effectors with an emphasis on cancer, inflammation and
      neurodegenerative diseases. The principle derived from the peptidic inhibitors
      has led to discoveries of the first generation of small molecule inhibitors of
      Rac GTPase of the Rho family. The implication of these studies in the
      pathobiology of various human diseases makes targeting Rho GTPases a valid
      strategy for future therapies.

PMID- 19601838
TI  - The roles of antimicrobial peptides in innate host defense.
AB  - Antimicrobial peptides (AMPs) are multi-functional peptides whose fundamental
      biological role in vivo has been proposed to be the elimination of pathogenic
      microorganisms, including Gram-positive and -negative bacteria, fungi, and
      viruses. Genes encoding these peptides are expressed in a variety of cells in the
      host, including circulating phagocytic cells and mucosal epithelial cells,
      demonstrating a wide range of utility in the innate immune system. Expression of
      these genes is tightly regulated; they are induced by pathogens and cytokines as
      part of the host defense response, and they can be suppressed by bacterial
      virulence factors and environmental factors which can lead to increased
      susceptibility to infection. New research has also cast light on alternative
      functionalities, including immunomodulatory activities, which are related to
      their unique structural characteristics. These peptides represent not only an
      important component of innate host defense against microbial colonization and a
      link between innate and adaptive immunity, but also form a foundation for the
      development of new therapeutic agents.

PMID- 19601846
TI  - Modulating proteostasis: peptidomimetic inhibitors and activators of protein
      folding.
AB  - Protein folding in the cell is a complex process with a fine balance between
      productive and non-productive folding. To modulate, either up-regulating or down
      regulating, the level of one specific protein with multiple approaches is
      possible, including the modulation of catalysed protein folding, the use of
      chemical and pharmacological chaperones, alteration of natural protein-protein
      interactions, the regulation of degradative pathways and manipulation of natural
      control mechanisms, such as the heat shock response and the unfolded protein
      response. Errors in proteostasis are linked to a wide range of disease states and
      many examples exist of the successful manipulation of proteostasis for the
      partial or complete elimination of the disease phenotype, including for many
      amyloid based diseases such as Parkinson's and Alzheimer's as well as for 'loss
      of-function' diseases such as Fabry's and Gaucher's diseases. This review takes
      an overview of the different approaches that can be used to alter proteostasis
      with an emphasis on peptidomimetic inhibitors and activators of protein folding.
      It covers the modulators available, their mechanisms of action and potential
      limitations, including the problems of specificity in altering proteostasis.

PMID- 19601847
TI  - Therapeutic potential of peptide motifs against HIV-1 reverse transcriptase and
      integrase.
AB  - Multiple clinical benefits have been obtained thanks to the combination of drugs
      targeting several steps of the HIV-1 replication. However, despite such
      combination therapy, complete eradication of the virus cannot be attained.
      Moreover, emergence of resistance observed under treatment and the lengthening
      life expectancy of treated patients highlight the need for new anti-HIV agents.
      Peptide-based compounds that exhibit anti RT and anti integrase activities were
      particularly described. Active peptides have been obtained from several ongoing
      approaches. The study of interaction between viral proteins inside the
      preintegration complex, and the growing knowledge of interactions between viral
      proteins and cellular partners, have generated a useful source of data for the
      development of peptide inhibitors. Recent data were also obtained from the
      observation that viral enzymes such as RT and integrase are fully active when
      they are in a dimeric (RT) or oligomeric state. Peptides derived from the
      interface of dimers are also of interest. The obtention of efficient small
      molecules as competitive oligomerization inhibitors is problematic, but anyway,
      improved cellular uptake and chemical modifications that were obtained in the
      past ten years allowed numerous peptide drugs to reach the clinic. Finally, a new
      promising class of peptide inhibitors is emerging called "shiftides", which
      interfere with the ability of IN to adopt an oligomeric active state.

PMID- 19601848
TI  - Cyclin dependent kinases as attractive targets to prevent transcription from
      viral genomes.
AB  - Most viral treatments target the virus itself, providing very specific effects
      and limiting side-effects on uninfected cells. However, this strategy of drug
      design often results in resistant viruses, especially among RNA viruses.
      Therefore, the focus has turned to drugs that target cellular proteins that are
      essential for viral replication, but not for cellular viability. Pharmacological
      CDK inhibitors are a prime example of this type of approach. Reviewed within are
      the various functions of CDKs, their role in the life cycle of selected
      Retroviruses and Herpesviruses, and the pharmacological CDK inhibitors that have
      been focused on in terms of viral inhibition.

PMID- 19601850
TI  - Statins and cardiovascular events in patients with end-stage renal disease on
      hemodialysis. The AURORA results suggest the need for earlier intervention.
AB  - The recently published Assessment of Survival and Cardiovascular Events (AURORA)
      trial showed that rosuvastatin (10 mg/d) compared with placebo did not result in
      a significant reduction in vascular events despite a 43% fall in low density
      lipoprotein cholesterol (LDL-C) levels in patients with end-stage renal disease
      (ESRD). The reasons for this and previous negative findings are discussed. In
      contrast, there is evidence that statins exert a nephroprotective action in less
      advanced chronic kidney disease (CKD). There is need for further trials to
      establish if patients at various stages of CKD will benefit from statin treatment
      in terms of both nephroprotection and reduction in vascular events.

PMID- 19601849
TI  - Therapeutic potential of peptide motifs--part II.

PMID- 19601852
TI  - Future challenges for microsomal transport protein inhibitors.
AB  - Atherosclerosis is a leading cause of morbidity and mortality worldwide. Statins
      are established as first choice drugs for the management of hyperlipidaemia and
      cardiovascular risk. However, a residual cardiovascular risk, partially
      attributable to lipids, remains even after statin treatment. This risk appears to
      be associated with both high-density lipoprotein cholesterol and triglyceride
      lipid fractions. Several novel therapeutic approaches have been proposed to
      reduce lipid levels. Microsomal transfer protein (MTP) is involved in the
      assembly of very-low-density lipoprotein and chylomicron lipoprotein particles in
      the liver and the gut, respectively. In the preclinical setting, various agents
      that affect activity of MTP have shown that inhibition can result in profound
      reductions in blood triglycerides and cholesterol. Similarly, evidence of
      efficacy using the target has been confirmed in man with small molecule
      inhibitors and antisense oligonucleotides. Unfortunately, despite their efficacy
      in reducing lipids, the clinical utility of small molecule inhibitors has been
      restricted by their potential to induce hepatic steatosis. Continuing attempts to
      utilise this clinical target (to decrease cholesterol, triglycerides and weight)
      have involved the use of lower doses or non systemically absorbed MTP inhibitors.

PMID- 19601851
TI  - Expression and function of anti-inflammatory interleukins: the other side of the
      vascular response to injury.
AB  - Common to multiple vascular diseases, including atherosclerosis, interventional
      restenosis, and transplant vasculopathy, is a localized inflammatory reaction.
      Activated vascular smooth muscle cells (VSMC) respond to local inflammation and
      migrate from the media into the lumen of the vessel where they proliferate and
      synthesize cytokines which they respond to in an autocrine fashion, sustaining
      the progression of the lesion. The deleterious effects of pro-inflammatory
      cytokines, particularly immunomodulatory interleukins, on vascular
      pathophysiology and development of these maladaptive processes have been the
      subject of intense study. Although a great deal of attention has been given to
      the negative effects of pro-inflammatory cytokines and interleukins, relatively
      little has been reported on the potentially beneficial paracrine and autocrine
      effects of anti-inflammatory interleukins on the vascular response to injury. The
      vast majority of emphasis on secretion and function of anti-inflammatory
      mediators has been placed on leukocytes. Consequently, the role of non-immune
      cells, and direct effects of anti-inflammatory interleukins on vascular cells is
      poorly understood. We will review the molecular mechanisms whereby anti
      inflammatory interleukins inhibit signal transduction and gene expression in
      inflammatory cells. We will review studies in which beneficial "indirect" effects
      of anti-inflammatory interleukins on progression of vascular disease are achieved
      by modulation of immune function. We will also present the limited studies in
      which "direct" effects of these interleukins on VSMC and endothelial cells dampen
      the vascular response to injury. We propose that expression of immunomodulatory
      cytokines by activated vasculature may represent an auto-regulatory feed back
      mechanism to promote resolution of the vascular response to injury.

PMID- 19601853
TI  - The complement cascade: new avenues in stroke therapy.
AB  - Recent evidence has shown that after the initial occlusion, a large portion of
      stroke patients achieve some degree of reperfusion either through collateral
      circulation or clot dissolution. However, it appears that this reperfusion may
      lead to increased inflammation-induced damage. Even though the exact mechanism of
      this secondary injury is unclear, several experimental studies have indicated an
      intimate connection between complement and this secondary form of damage. We
      review the available literature and attempt to identify promising clinical
      therapeutic targets.

PMID- 19601855
TI  - Pharmacological agents in the treatment of venous disease: an update of the
      available evidence.
AB  - Varicose veins and the complications of venous disease are thought to affect over
      a quarter of the adult population and the management of these conditions are a
      major cause of health service expense. Advances in the understanding of venous
      pathophysiology have highlighted numerous potential targets for pharmacotherapy.
      This review considers the evidence for pharmacological agents used for the
      treatment of chronic venous disease. A literature search using Pubmed, Embase and
      Cinahl databases was performed. The initial search terms 'varicose vein', 'venous
      ulcer' and 'venous disease' were used with appropriate search limits to identify
      prospective studies of pharmacotherapy in venous disease. A wide range of
      venoactive and non-venoactive drugs have been studied in patients with venous
      disease. The use of micronized purified flavonoid fraction (Daflon) can reduce
      symptoms of pain, heaviness and oedema in patients with venous reflux and a
      recent meta-analysis concluded that Daflon improves healing in patients with
      venous ulceration treated with compression. Pentoxifylline may be a useful
      adjunct to compression therapy for patients with venous ulceration. Oxerutins and
      calcium dobesilate may be of benefit in reducing oedema and rutosides may help to
      relieve the symptoms of varicose veins in pregnancy. The clinical benefits of
      other medications remain unproven. Although numerous pharmacological agents have
      been proposed and studied, Daflon has demonstrated the greatest clinical benefits
      in patients with venous disease. Further research is needed to define the role of
      venoactive drugs in clinical care and improve our understanding of the
      pathophysiology of venous disease to help identify new therapeutic avenues.

PMID- 19601856
TI  - New anticoagulants: focus on venous thromboembolism.
AB  - Anticoagulation is recommended for prophylaxis and treatment of venous
      thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) and/or
      arterial thromboembolism. The therapeutic arsenal of anticoagulants available to
      clinicians is mainly composed by unfractionated heparin (UFH), low-molecular
      weight heparin (LMWH), fondaparinux and oral vitamin K antagonists (VKA) (i.e.
      warfarin and acenocumarol). These anticoagulants are effective, but they require
      parenteral administration (UFH, LMWH, fondaparinux) and/or frequent anticoagulant
      monitoring (intravenous UFH, oral VKA). Novel anticoagulants in clinical testing
      include orally active direct factor II inhibitors [dabigatran etexilate (BIBR
      1048), AZD0837)], parenteral direct factor II inhibitors (flovagatran sodium),
      orally active direct factor X inhibitors [rivaroxaban (BAY 59-7939), apixaban,
      betrixaban, YM150, DU-176b, LY-517717, GW813893, TAK-442, PD 0348292] and new
      parenteral FXa inhibitors [idraparinux, idrabiotaparinux (biotinilated
      idraparinux; SSR 126517), ultra-low-molecular-weight heparins (ULMWH: AVE5026, RO
      14)]. These new compounds have the potential to complement heparins and
      fondaparinux for short-term anticoagulation and/or to replace VKA for long-term
      anticoagulation in most patients. Dabigatran and rivaroxaban have been the firsts
      of the new oral anticoagulants to be licensed for the prevention of VTE after hip
      and knee replacement surgery. In the present review, we discuss the pharmacology
      of new anticoagulants, the key points necessary for interpreting the results of
      studies on VTE prophylaxis and treatment, the results of clinical trials testing
      these new compounds and their potential advantages and drawbacks over existing
      therapies.

PMID- 19601854
TI  - Ginseng compounds: an update on their molecular mechanisms and medical
      applications.
AB  - Ginseng is one of the most widely used herbal medicines and is reported to have a
      wide range of therapeutic and pharmacological applications. Ginsenosides, the
      major pharmacologically active ingredients of ginseng, appear to be responsible
      for most of the activities of ginseng including vasorelaxation, antioxidation,
      anti-inflammation and anti-cancer. Approximately 40 ginsenoside compounds have
      been identified. Researchers now focus on using purified individual ginsenoside
      to reveal the specific mechanism of functions of ginseng instead of using whole
      ginseng root extracts. Individual ginsenosides may have different effects in
      pharmacology and mechanisms due to their different chemical structures. Among
      them the most commonly studied ginsenosides are Rb1, Rg1, Rg3, Re, Rd and Rh1.
      The molecular mechanisms and medical applications of ginsenosides have attracted
      much attention and hundreds of papers have been published in the last few years.
      The general purpose of this update is to provide information of recently
      described effects of ginsenosides on antioxidation, vascular system, signal
      transduction pathways and interaction with receptors. Their therapeutic
      applications in animal models and humans as well as the pharmacokinetics and
      toxicity of ginsenosides are also discussed in this review. This review concludes
      with some thoughts for future directions in the further development of ginseng
      compounds as effective therapeutic agents.

PMID- 19601857
TI  - Omega-3 polyunsaturated fatty acids: their potential role in blood pressure
      prevention and management.
AB  - Omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) from fish and fish oils
      appear to protect against coronary heart disease: their dietary intake is in fact
      inversely associated with cardiovascular disease morbidity/mortality in
      population studies. Recent evidence suggests that at least a part of this
      protective effect is mediated by a relatively small but significant decrease in
      blood pressure (BP) level. In fact, omega-3 PUFAs exhibit wide-ranging biological
      actions that include regulating both vasomotor tone and renal sodium excretion,
      partly competing with omega-6 PUFAs for common metabolic enzymes and thereby
      decreasing the production of vasoconstrictor rather than vasodilator and anti
      inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme (ACE)
      activity, angiotensin II formation, Tumor Growth Factor-beta (TGF-beta)
      expression, enhance endothelial nitric oxide (NO) generation and activate the
      parasympathetic nervous system. The final results are improved vasodilation and
      arterial compliance of both small and large arteries. Preliminary clinical trials
      involving normotensive and hypertensive dyslipidaemic patients, diabetics and
      elderly subjects, confirm this working hypothesis: 3 meta-analyses suggest that
      PUFAs are able to slightly, but significantly improve arterial hypertension.
      Future research will clarify if PUFA supplementation could improve the
      antihypertensive action of specific BP lowering drug classes and of statins.

PMID- 19601858
TI  - Adverse bioeffects of ultrasound contrast agents used in echocardiography: true
      safety issue or "much ado about nothing"?
AB  - Ultrasound contrast agents, consisting of gas-filled microbubbles, have long been
      used to enhance ultrasonographic imaging of various organs and in several
      settings. In echocardiography, after their first use for Doppler signal
      enhancement, their applications have expanded and several studies, combining a
      range of stress modalities with myocardial contrast echocardiography have shown
      the clinical utility of these agents. In experimental isolated heart animal
      models, the interaction of ultrasound with echo-contrast microbubbles was shown
      to have significant biologic effects when the acoustic energy of the beam
      exceeded a threshold, leading them to rupture and causing cavitation phenomena;
      the observed consequences in the experimental setting included microvascular
      damage, transient decrease of contractile performance and increased lactate
      production. From the clinical point of view, the reporting of a number of serious
      adverse events - whose association with the echo-contrast agents was debated -
      has led to the addition of warning boxes in the prescribing documentation of
      these preparations. On the other hand, clinical studies including high numbers of
      patients have shown good safety and tolerance of contrast use during stress
      echocardiography, both for left ventricle opacification and myocardial perfusion
      imaging. The present review aims at presenting a balanced account of the existing
      data regarding the mechanisms and clinical implications of echo-contrast
      bioeffects, in order to make an informed assessment of their safety in clinical
      practice.

PMID- 19601859
TI  - Blockade of neoangiogenesis, a new and promising technique to control the growth
      of malignant tumors and their metastases.
AB  - Neoangiogenesis, the development of new blood vessels from a pre-existing
      vasculature involves the migration behavior, proliferation and differentiation of
      endothelial cells. This process is an important aspect to both the growth and
      metastasis of solid tumors. In growing tumors, the development of a sufficient
      vascular supply is a highly complex event, which is controlled by many factors.
      An interaction between tumor cells, endothelial cells, macrophages, fibroblasts,
      and the extracellular matrix, all of which are capable of releasing factors
      influencing the angiogenic mechanisms is necessary for the building of new
      sufficient vascular structures. The increased understanding of the balance of
      angiogenesis and mechanisms of vascular control allowed the development of new
      therapeutic substances that influence that process in different ways. For
      example, work done over the last decade has elucidated the central role of
      vascular endothelial growth factor (VEGF) in the regulation of normal and
      pathological angiogenesis. Therefore, the blockade of VEGF signaling is currently
      a major part of strategies for the therapy of malignant tumors. Several studies
      tested neutralizing antibodies against mature VEGF protein or its isoforms,
      blockade of VEGF receptors by VEGF receptor antibodies, soluble VEGF receptor
      mutants or fusion-proteins and finally, intracellular interference with VEGF mRNA
      or signaling in the target cell. In this review, we present strategies and
      substances for the blockade of neoangiogenesis that are already in clinical use
      or in pre-clinical trials. Also the combination of these approaches with
      conventional chemotherapy or radiotherapy will be discussed.

PMID- 19601860
TI  - Role of pharmacotherapy in cardiac ion channelopathies.
AB  - In the last decade there have been considerable advances in the understanding of
      the pathophysiology of malignant ventricular tachyarrhythmias (VA) and Sudden
      Cardiac Death (SCD). Over 80% of SCD occurs in patients with organic heart
      disease. However, approximately 10-15% of SCD occurs in the presence of
      structurally normal heart and the majority of those patients are young. In this
      group of patients, changes in genes encoding cardiac ion channels produce
      modification of the function of the channel resulting in an electrophysiological
      substrate of VA and SCD. Collectively these disorders are referred to as Cardiac
      Ion Channelopathies. The 4 major syndromes in this group are: The Long QT
      Syndrome (LQTS), the Brugada Syndrome (BrS), the Short QT Syndrome (SQTS), and
      the Catecholaminergic Polymorphic VT (CPVT). Each of these syndromes includes
      multiple subtypes with different and sometimes complex genetic abnormalities of
      cardiac ion channels. Many are associated with other somatic and neurological
      abnormalities besides the risk of VA and SCD. The current management of cardiac
      ion channelopathy could be summarized as follows: 1) in symptomatic patients, the
      implantable cardioverter defibrillator (ICD) is the only viable option; 2) in
      asymptomatic patients, risk stratification is necessary followed by the ICD,
      pharmacotherapy, or a combination of both. A genotype-specific approach to
      pharmacotherapy requires a thorough understanding of the molecular-cellular basis
      of arrhythmogenesis in cardiac ion channelopathies as well as the specific drug
      profile.

PMID- 19601861
TI  - Clinical aspects of melatonin in the acute coronary syndrome.
AB  - This review considers the actions of an endogenously produced molecule,
      melatonin, on heart diseases. Recent research has shown that inflammation plays a
      key role in coronary heart disease (CHD) and other manifestations of
      atherosclerosis. Immune cells dominate early atherosclerotic lesions, their
      effector molecules accelerate progression of the lesions and activation of
      inflammation can elicit acute coronary syndromes (ACS). Scientific evidence from
      the last 15 years has suggested that melatonin has positive effects on the
      cardiovascular system. The presence of vascular melatoninergic receptor binding
      sites has been demonstrated; these receptors are functionally linked to
      vasoconstrictor or vasodilatory effects of melatonin. It has been shown that
      patients with CHD have a low melatonin production rate, especially those with
      higher risk of cardiac infarction and /or sudden death. Similarly to other organs
      and systems, the cardiovascular system exhibits diurnal and seasonal rhythms,
      including those in the heart rate, cardiac output and blood pressure. The
      suprachiasmatic nuclei of hypothalamus and, possibly, the melatoninergic system
      modulate the cardiovascular rhythms. The melatonin attenuates molecular and
      cellular damages resulting from cardiac ischemia/reperfusion in which destructive
      free radicals are involved. Anti-inflammatory and antioxidative properties of
      melatonin are also involved in the protection against vascular disease, i.e.
      atherosclerosis. The current brief summary of the literature provides an overview
      on the role of melatonin in the ACS.

PMID- 19601862
TI  - Arterial accelerated aging in dialysis patients: the clinical impact of vascular
      calcification.
AB  - Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) is a systemic disorder
      of mineral and bone metabolism that occurs in Chronic Kidney Disease (CKD). In
      addition to abnormalities in serum calcium (Ca) and phosphate (P) profile, CKD
      MBD is characterized by abnormalities of bone turnover, mineralization, volume
      and growth as well as vascular calcification (VC). Indeed, the co-localization of
      bone markers such as Osteopontin, Alkaline Phosphatase and Osteocalcin along with
      osteoblast-like cells in the contest of the arterial wall of uremic patients,
      indicate that VC is an active biological process with peculiar analogies with
      bone mineralization. Thus, VC represents a plausible link between Ca and P
      derangements and the increased mortality associated with CKD-MBD. The process of
      VC starts in early stages of CKD and patients with CKD-3, -4 and -5 not
      undergoing haemodialysis may present a significant burden of calcification in the
      coronaries. Considering that presence and extent of VC in CKD portend poor
      prognosis, many efforts have been made to shed light on this complicated
      phenomenon to prevent VC deposition and progression. Indeed, careful control of
      calcium load, serum P and parathyroid hormone along with the use of calcium-free
      P binders and vitamin D analogs represent our current armamentarium to improve
      quality of life and reduce mortality in CKD. We herein summarize the current
      understanding and evidence supporting strategies available for VC treatment.

PMID- 19601863
TI  - Mesenchymal stem cells: a good candidate for restenosis therapy?
AB  - Restenosis is a pathophysiological phenomenon that can occur in patients
      submitted to revascularization procedures (bypass, endarterectomy, angioplasty),
      possibly resulting in new narrowing of injured vessels. Vascular restenosis
      remains a pressing clinical problem, despite the therapeutic strategies and
      devices developed so far. Stem cells hold a great potential for the regeneration
      of damaged tissues in cardiovascular diseases. Recent studies clearly indicated
      that different stem cell populations contribute to vascular remodeling after
      injury. Nevertheless, the exact role of vascular cell precursors in restenosis
      pathophysiology is not yet well defined, as heterogeneous and contrasting data
      are currently available. Mesenchymal stromal/stem cells (MSCs) are non
      hematopoietic multi-potent stem-like cells able of differentiating into both
      mesenchymal and non-mesenchymal lineages. MSCs offer a series of advantages: a)
      they can be isolated from a small aspirate of bone marrow; b) extensively
      proliferate in vitro while preserving a normal karyotype and telomerase activity
      on several passages; c) express low immunogenicity and hence their use should not
      require a pharmacological immunosuppression. MSCs have an intrinsic ability to
      differentiate into functional cell types able to repair the diseased or injured
      tissue in which they are localised. For this reason, MSCs are currently under
      scrutiny for treatment of different cardiovascular diseases. Nevertheless, it has
      not yet been clearly determined whether MSCs can substantially contribute to a
      positive resolution of restenosis after vascular injury. This review will provide
      information about the mechanisms at the basis of vascular restenosis and the
      current knowledge of the role, positive or negative, played by MSCs in restenosis
      progression as highlighted by recent experimental protocols.

PMID- 19601864
TI  - Current management of intermittent claudication: the role of pharmacological and
      nonpharmacological symptom-directed therapies.
AB  - Lower extremity peripheral arterial disease (PAD) is a manifestation of
      atherosclerosis, with a prevalence ranging from 4% to 12% in the adult population
      and increasing up to 20% in older individuals. Intermittent claudication (IC) may
      markedly impair walking ability, overall functional status and quality of life.
      PAD is a marker of systemic atherosclerosis and is associated with increased
      cardiovascular morbidity and mortality. However, leg disease usually runs a
      rather benign course in claudicant patients, with only about 1% to 3% of them
      ever requiring a major amputation over a 5-year period. The goals of treatment
      for claudication are to relieve exertional symptoms, and improve walking capacity
      and quality of life. Therapeutic strategies aimed at reducing systemic
      cardiovascular risk burden and prolonging survival, including intensive risk
      factor modification and antiplatelet therapy, should be implemented in all
      patients with PAD. Supervised exercise training has proven the most effective
      conservative treatment for symptomatic relief of IC. Current evidence for drug
      therapy of IC supports the use of cilostazol as a first-line drug. Other drugs
      with more limited evidence of benefit for claudication include pentoxifylline and
      naftidrofuryl. Endovascular or surgical revascularization is indicated for
      selected patients with vocation- or lifestyle-limiting claudication who are
      unresponsive to exercise and pharmacotherapy. New drug candidates for managing
      claudication symptoms include propionyl-L-carnitine and statins. Preliminary
      studies suggest that therapeutic angiogenesis holds promise for future treatment
      of IC.

PMID- 19601865
TI  - Vitamin D and cardiovascular disease.
AB  - Cardiovascular disease (CVD) is a major cause of morbidity and mortality
      worldwide. Recently vitamin D deficiency has been identified as a potential risk
      factor for many diseases not traditionally associated with vitamin D, such as
      cancer and CVD. This review discusses the evidence suggesting an association
      between low 25-hydroxyvitamin D levels and CVD and the possible mechanisms
      mediating it. Vitamin D deficiency has been associated with CVD risk factors such
      as hypertension and diabetes mellitus, with markers of subclinical
      atherosclerosis such as intima-media thickness and coronary calcification as well
      as with cardiovascular events such as myocardial infarction and stroke as well as
      congestive heart failure. It could be suggested that vitamin D deficiency
      contributes to the development of CVD through its association with risk factors,
      such as diabetes and hypertension. However, direct effects of vitamin D on the
      cardiovascular system may also be involved. Vitamin D receptors are expressed in
      a variety of tissues, including cardiomyocytes, vascular smooth muscle cells and
      endothelial cells and vitamin D has been shown to affect inflammation and cell
      proliferation and differentiation. While much evidence supports a potential
      antiatherosclerotic effect of vitamin D, prospective, placebo-controlled
      randomized as well as mechanistic studies are needed to confirm this association.
      Since vitamin D deficiency is easy to screen for and treat, the confirmation of
      such an association could have important implications for both, patient care and
      health policy.

PMID- 19601866
TI  - Differences in lopinavir plasma concentrations comparing Kaletra film coated
      tablets and soft gelatine capsules that result in various lipid abnormalities.
AB  - Changes in lipids and lopinavir plasma concentrations were examined in 40 HIV
      patients exposed to lopinavir/ritonavir 400/100 mg BID, formulated as tablets and
      as capsules. Triglycerides and total/HDL-cholesterol ratio were significantly
      lower with tablets than with capsules. Lopinavir concentrations were higher with
      tablets than with capsules.

PMID- 19601867
TI  - Esterase activities in the blood, liver and intestine of several preclinical
      species and humans.
AB  - Species and tissue differences in the activity of three major classes of
      esterases, carboxylesterase (CE), butyrylcholinesterase (BChE) and paraoxonase
      (PON), were studied. Substantial species differences in activity of these
      esterases were observed between the mouse, rat, dog monkey and human. Such
      species differences must be considered when using these preclinical species to
      optimize the pharmacokinetic properties of ester compounds intended for human
      use.

PMID- 19601868
TI  - High throughput quantitative assessment of CYP inactivation using 2 concentration
      points.
AB  - To provide a fast and quantitative assessment of CYP inactivation in the drug
      discovery stage, a mathematical model was derived to calculate enzyme
      inactivation parameters, k(inact) and K(I), based on experimental data obtained
      from 2 concentrations of enzyme inactivator. With CYP3A4 inactivators across a
      range of inactivation potencies, this novel method provided expected rank
      ordering of CYP3A4 inactivation. Furthermore, the k(inact) and K(I) values
      obtained in the two-concentration format correlate generally well with the
      parameters obtained in the six-concentration format.

PMID- 19601869
TI  - Inhibition of human aromatase by myosmine.
AB  - Myosmine, a minor tobacco alkaloid widely occurring in food products of plant and
      animal origin, inhibits the conversion of testosterone to estradiol by human
      aromatase (IC(50): 33+/-2 microM) sevenfold more potent than nicotine (IC(50):
      223+/-10 microM) and may have implications for sexual hormone homoeostasis.

PMID- 19601870
TI  - Electronic and structural aspects of p450-mediated drug metabolism.
AB  - From a consideration of first principles for enzymes kinetics, we have employed
      theoretical methods which enable one to analyse the kinetics of cytochrome P450
      mediated reactions which have been based on the known physicochemical principles
      underlying the majority of chemical or enzymatic reactions. A comparison is made
      between the correlation equations produced from the QSAR analysis of experimental
      P450 reaction rate data and those obtained from first principles, where there
      appears to be a generally satisfactory concordance between the two procedures. In
      this respect, we have developed expressions based on standard reaction kinetics
      theory which incorporate the Eyring and Marcus relationships. The analysis of
      P450-catalyzed reaction rates is elaborated to encompass a treatment of metabolic
      clearance, and satisfactory correlations are obtained with literature values for
      both intrinsic clearance and whole body clearance in terms of compound
      lipophilicity derived from log P data, where P is the octanol/water partition
      coefficient. The importance of ionization potential as a factor in the overall
      catalytic turnover of P450-mediated reactions is noted, especially in combination
      with the lipophilicity parameter, log P.

PMID- 19601871
TI  - Glucuronidation of buprenorphine and norbuprenorphine by human liver microsomes
      and UDP-glucuronosyltransferases.
AB  - We investigated the enzyme kinetics of buprenorphine and norbuprenorphine
      glucuronidation in human liver microsomes and UDP-glucuronosyltransferase (UGT)
      Supersomes. The involvement of UGT 1A1, 1A3 and 2B7 in buprenorpine and 1A3 in
      norbuprenorphine glucuronidation were confirmed. Novel involvement of 2B17 with
      buprenorphine and 1A1 with norbuprenorphine were demonstrated. Scaling of
      buprenorphine clearance with, or without, correction for the nonspecific
      microsomal protein binding of buprenorphine (f(u) = 0.42) suggested
      glucuronidation was a significant route for hepatic clearance of buprenorphine.

PMID- 19601872
TI  - High-throughput evaluation of CYP1A1 and 2B1 induction in rat liver slices using
      a semi-automated system.
AB  - Drug candidates with the propensity to induce rat CYP1A1 or 2B1 isoforms are
      believed to possess a greater tendency to induce hepatic tumors in oncogenicity
      studies. We have previously published on a manual rat liver slice assay that
      showed a satisfactory relationship between in vitro CYP2B1 m-RNA induction using
      real time PCR and the ex vivo pentoxyresorufin O-dealkylase (PROD) activity in
      liver microsomes prepared from rats treated daily via the oral route for 14
      consecutive days with inducers or non-inducers. We now describe this automated in
      vitro high throughput liver slice technique to screen out drug candidates that
      are potent rodent CYP1A1 and/or CYP2B1 inducers. A good concordance between in
      vitro and in vivo data was observed for both CYP1A1 (100 %) and CYP2B1 (90%)
      isoforms. Automation of key steps has enabled us to increase the annual screening
      throughput from 200 (manual) to 1500 compounds. The increase in throughput
      allowed the quick development of structure-induction relationships (SIR's) for
      multiple drug discovery programs in a facile manner.

PMID- 19601873
TI  - A comparative study on the stability of silybin and that in silymarin in buffers
      and biological fluids.
AB  - Pure silybin was found to be unstable whilst silybin in silymarin was stable in
      buffers from pH 1.0 to 7.8. The metabolism of silybin was more severe when in its
      pure form as compared to silybin in silymarin, as tested in a range of biological
      fluids including plasma, intestinal fluid and liver homogenates. It would appear
      that components in silymarin have a stabilization effect on its main component
      silybin.

PMID- 19601874
TI  - Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate
      treated albino mice.
AB  - Anabolic androgenic steroids are the xenobiotic substrates that are metabolized
      in the body by the protective enzyme systems. Mixed function oxygenase enzymes
      include a group of enzymes which play an essential role in the metabolism of a
      broad range of xenobiotics including endogenous and exogenous substrates.
      Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an
      important role in oxidative metabolism of drugs and xenobiotics entering human
      body. Various anabolic steroids are found either to increase or decrease the
      activity of cytochrome P-450. However, effect of nandrolone decanoate, most
      commonly abused anabolic steroid, on cytochrome P-450 activity is still
      fragmentary. In the present study, albino mice were administered intramuscular
      2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450
      activity is determined by following the method of Omura and Sato (1964) in liver
      and kidney tissues of both normal and experimental groups upto 90 days.
      Investigation shows a significant (p <0.01) increase of cytochrome P-450
      (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A
      tissue specific and dose specific increase of cytochrome P-450 activity is
      observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day
      whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From
      the above observation, nandrolone decanoate can be suggested as a potent inducer
      of cytochrome P-450 activity like other anabolic steroids.

PMID- 19601875
TI  - Inhibitory properties of trapping agents: glutathione, potassium cyanide, and
      methoxylamine, against major human cytochrome p450 isoforms.
AB  - In the early stages of drug discovery, the formation of reactive metabolites is
      often assessed by co-incubating the drug in liver microsomes with a trapping
      agent in the presence of NADPH. Our group assessed the capability of commonly
      used trapping agents to reversibly inhibit major cytochrome P450 (CYP) isoforms.
      Glutathione and cyanide did not inhibit the enzymes at concentrations up to 10
      mM; however methoxylamine did show inhibition, with IC(50) values of 0.53 mM for
      CYP1A2, 4.12 mM for CYP2C9, 2.04 mM for CYP2C19, 9.72 mM for CYP2D6, and 1.26 and
      >10 mM for CYP3A4/5 (for testosterone and midazolam, respectively, as
      substrates).

PMID- 19601876
TI  - Controversial effects of non-steroidal anti-inflammatory drugs on bone: a review.
AB  - Bone turnover is much important in normal homeostasis of body skeleton.
      Medications, nutritional status, and systemic illnesses may affect bone
      metabolism by altering biochemical mediators. Prostaglandins, especially of E and
      F series are much important in bone physiology by affecting osteoclastic activity
      and osteoblastic differentiation. In bone fracture, production of prostaglandins
      affects fracture healing. There is the possibility that non-steroidal anti
      inflammatory drugs (NSAIDs) affect bone health by inhibiting cyclooxygenase (COX)
      enzymes which reduce synthesis of prostaglandins. The aim of this paper is to
      review the effects of NSAIDs on bone by evaluating both animal and human studies.
      Using key words such as bone, bone marker, bone mineral density, NSAIDs, COX
      inhibitor, bone metabolism and search engines like Web of sciences, Scopus,
      Pubmed, and Google scholar, all relevant studies were collected. Although NSAIDs
      showed anti-resorptive properties in animal studies and some few human studies,
      to date no conclusive result has been observed in bone formation. Some limited
      studies reported higher bone mineral density in daily users of NSAIDs.

PMID- 19601877
TI  - The airway neurogenic inflammation: clinical and pharmacological implications.
AB  - Bronchial airway microvasculature consists in a developed network of vessels,
      which plays an important role in normal homeostasis as well as in inflammatory
      airway processes. Its airway autonomic neural control includes cholinergic and
      adrenergic innervation, as well as nonadrenergic noncholinergic system. The
      nerve/vessel interplay is complex and not yet completely clarified. In response
      to inspired air conditions, the sensory nerves can recruit appropriate reflexes,
      which can induce different vascular processes, such as vasodilatation,
      vasoconstriction, plasma extravasation and exudation. Additionally, the
      stimulation of C fibres may result in an axon local reflex with antidromic
      conduction down afferent nerve collaterals and release of sensory neuropeptides,
      which in turn may act on the mucosal vasculature to promote vasodilatation and
      microvascular leakage. The neurogenic inflammation may play a key role in
      allergic diseases, such as asthma, as well as in COPD, a smoking-related disease.
      This review deals with the interactions of vessels and nerves within the airway
      mucosa under healthy conditions and in inflammatory diseases. The clinical and
      pharmacological implications are also described.

PMID- 19601878
TI  - Platelet activating factor/platelet activating factor receptor pathway as a
      potential therapeutic target in autoimmune diseases.
AB  - Platelet activating factor (PAF) is a phospholipid mediator of inflammation that
      is released early in inflammation by a variety of cell types. PAF acts largely by
      binding to its receptor, PAF-R, a G-protein coupled receptor found on a variety
      of cells, including cells of the immune system. PAF has been implicated in the
      pathogenesis of asthma and allergic conditions, but its role in autoimmune
      conditions has been less extensively investigated. Here, we review the
      accumulating evidence for the role of PAF/PAF-R pathway in autoimmune diseases.
      We describe studies showing up-regulation of PAF-R in inflammatory bowel disease,
      rheumatoid arthritis and multiple sclerosis and review the evidence from the use
      of PAF-R antagonists. We describe results of experimental models of inflammatory
      diseases that point to a role for PAF/PAF-R pathway including those using PAF-R
      antagonists and those employing PAF-R knockout mice and knockout mice for
      cytosolic phospholipase2. Recent experiments from our laboratory show that
      PAF/PAF-R pathway may influence T cell responses and favour the Th17 phenotype
      (in which T cells produce tissue destructive proinflammatory cytokine IL-17). The
      PAF/PAF-R pathway is a promising target for pharmacological intervention in
      autoimmune diseases.

PMID- 19601879
TI  - Toll-like receptors and kidney diseases.
AB  - Toll like receptors (TLRs) have been extensively studied since their discovery in
      1997, and an increasingly detailed picture is emerging about their role in health
      and disease. TLRs, the first identified family of pattern recognition receptors,
      can recognize invaders through the exogenous pathogen-associated molecular
      patterns (PAMPs) and tissue injury through the endogenous danger-associated
      molecular patterns (DAMPs). In addition to immunocytes, TLRs are widely
      distributed in various cell types, including renal cells where they are thought
      to play a significant role in immune activation to pathogens, as well as the
      development and course of various kidney pathologies. This review summarizes the
      present data about the important role TLRs play in kidney diseases focusing on
      the specific role of PAMPs versus DAMPs and of local versus systemic TLR
      activation.

PMID- 19601880
TI  - Respiratory syncytial virus bronchiolitis and asthma - insights from recent
      studies and implications for therapy.
AB  - Infection with respiratory syncytial virus (RSV) is a leading cause of upper and
      lower respiratory tract infection in infants. It is accompanied by a considerably
      disease burden and a hospitalisation rate of up to 3% in infected infants.
      Besides, it is still a matter of intensive discussion whether severe RSV
      infection in early infancy causes the development of asthma later in live or
      whether RSV bronchiolitis just chronologically precedes asthma in children who
      are susceptible to asthma. The latter could be due to a common genetic background
      of both diseases predisposing to an exaggerated inflammatory response of the
      lungs to allergens and pathogens. Genetic studies might help to elucidate the
      mechanisms leading to both diseases and to highlight common as well as diverse
      pathways. The results of such investigations will influence the current
      understanding of the diseases and might even change our therapeutical approaches
      to both disorders. This review summarizes current findings in the genetics of
      bronchial asthma and severe RSV bronchiolitis. The question whether a
      relationship exists between severe RSV bronchiolitis in infancy and childhood
      asthma will also be discussed by taking recent epidemiological studies in
      account. A special focus is laid on the implications of these findings for a
      targeted drug therapy of both diseases.

PMID- 19601881
TI  - CD44 and its role in inflammation and inflammatory diseases.
AB  - The cell adhesion molecule CD44 is expressed on the majority of immune cells and
      is responsible for mediating adhesion to the extracellular matrix
      glycosaminoglycan, hyaluronan. The binding of CD44 to hyaluronan is induced on T
      lymphocytes after activation by antigen and on monocytes after stimulation by
      inflammatory agents. Under inflammatory conditions, CD44 on endothelial cells
      presents hyaluronan to CD44 on activated T lymphocytes and mediates a rolling
      interaction under flow conditions. This rolling interaction together with
      chemokine signaling upregulates integrin-mediated adhesion, which induces cell
      arrest and leads to subsequent migration to the inflammatory site. Studies with
      monoclonal antibodies against CD44 in mouse models of chronic inflammatory
      disease showed reduced disease severity attributed to reduced leukocyte
      recruitment. More recent investigations, taking advantage of the availability of
      CD44 null mice, further established a role for CD44 in leukocyte recruitment to
      inflammatory sites. These studies also revealed a role for CD44 in limiting the
      inflammatory response and resolving inflammation in models of lung injury and
      hepatitis. Here we describe the contributions of CD44 and hyaluronan to an
      inflammatory response and discuss the role of CD44 in both promoting and
      resolving inflammation in various mouse models of inflammatory disease.

PMID- 19601882
TI  - Migration and function of Th17 cells.
AB  - T cells play central roles in regulation of the immune system in mammals. T cell
      receptor alphabeta T cells that can produce the cytokine IL-17 are called Th17
      cells and form a lineage of effector T cells that are distinct from Th1, Th2 and
      FoxP3(+) T cells. The primary function of Th17 cells is to fight infection by
      bacterial and fungal pathogens. Autoreactive Th17 cells are implicated in
      mediating inflammation in the central nerves system, joints and other tissues.
      Th17 cells express a number of chemokine receptors including a secondary lymphoid
      tissue homing receptor (CCR7), the B follicle homing receptor (CXCR5), and non
      lymphoid tissue homing receptors (CCR4, CCR5, and CXCR6). While these receptors
      are heterogeneously expressed by Th17 cells and have the potential to guide the
      migration of Th17 cell subsets into various tissues, CCR6 is uniformly expressed
      by most Th17 cells regardless of their tissue tropism. CCR6 plays an important
      role in migration of Th17 cells to inflamed tissues. Another function of CCR6 is
      to localize Th17 cells close to CCL20 expressing cells in the intestine, which
      would be important for the homeostasis of Th17 cells. Thus, chemokine receptors
      appear to play complex roles in the biology of Th17 cells.

PMID- 19601883
TI  - Mechanism of action of flavonoids as anti-inflammatory agents: a review.
AB  - Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a
      variety of biological effects both in vitro and in vivo. They have been found to
      have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic,
      mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic,
      antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical
      effects, which inhibit a number of enzymes such as aldose reductase, xanthine
      oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They
      also have a regulatory role on different hormones like estrogens, androgens and
      thyroid hormone. They have been found to have anti-inflammatory activity in both
      proliferative and exudative phases of inflammation. Several mechanisms of action
      have been proposed to explain anti-inflammatory action of flavonoids. The aim of
      the present review is to give an overview of the mechanism of action of potential
      anti-inflammatory flavonoids.

PMID- 19601884
TI  - The role of anaphylatoxins C3a and C5a in regulating innate and adaptive immune
      responses.
AB  - C3a and C5a, the small (approximately 10KDa) cleavage fragments released by
      complement activation, are potent mediators of inflammation. They are
      anaphylatoxins and act as cell activators with nanomolar affinity, exerting their
      functions through binding to specific receptors (C3aR and C5aR or C5L2
      respectively). Recent studies suggest that locally generated complement effector
      molecules including C3a and C5a contribute to pathological processes in
      inflammatory and immunological diseases as well as adaptive immune response
      besides its host defence mechanism. Targeting the receptors and/or their ligands
      can reduce undesired inflammatory responses and tissue damage in certain
      pathological conditions. In this article we describe the recent developments in
      this important area and focus on the role of C3a/C5a in inflammatory and
      autoimmune diseases and in adaptive immune responses.

PMID- 19601885
TI  - HIV/AIDS: recent advances in antiretroviral agents.
AB  - Despite the considerable progress in antiretroviral therapy, the eradication of
      HIV-1 remains unfeasible. Therefore, novel agents are under investigation. The
      aim of this review is to summarize the conventional compounds, to describe the
      recently approved agents, and to take a comprehensive look at the clinically
      relevant findings of current research.

PMID- 19601886
TI  - Pharmacological and lifestyle factors modulating serum paraoxonase-1 activity.
AB  - Paraoxonase-1 is a lactonase and an esterase and it plays a protective role in
      toxicity as well as in diseases involving oxidative stress. Recently, insights
      into how it may be modulated by environmental factors have acquired clinical
      relevance. This article reviews the state-of-the-art evidence regarding PON1
      modulation by pharmacological products as well as nutritional and lifestyle
      factors.

PMID- 19601887
TI  - MicroRNA regulatory network in human colorectal cancer.
AB  - Epigenetic modifications include DNA methylation, histone modifications, and
      noncoding RNAs containing microRNAs (miRNA). miRNAs are small noncoding RNAs that
      are 21 to 25 nt in length; they downregulate gene expression during cell
      development, cell proliferation, cell differentiation, and apoptosis. They play a
      critical role in human carcinogenesis. Presently, evidences show that miRNAs
      participate as oncogenic miRNAs or tumor suppressors in the developmental and
      physiological processes of human colorectal cancer (CRC). Disturbed miRNA
      expression may be attributable to a mechanism involving multiple factors. In this
      review, we focus on the colorectal miRNA expression profile and further discuss
      the miRNA regulatory network involved in the tumorigenesis of human CRC. We,
      thus, hope to open up new avenues for anticancer therapy based on the epigenetic
      regulation of miRNA.

PMID- 19601888
TI  - Human- and virus-encoded microRNAs as potential targets of antiviral therapy.
AB  - It has recently been demonstrated that short RNA molecules, called microRNAs, are
      one of the major factors regulating the expression of human genes. There are
      several lines of evidence that microRNAs also play a key role in host-virus
      interactions. It is believed that both human- and virus-encoded miRNA will, in
      the nearest future, become very attractive targets of antiviral therapy.

PMID- 19601891
TI  - From fragment screening to potent binders: strategies for fragment-to-lead
      evolution.
AB  - To be an effective medicine a drug has to possess many attributes to ensure
      target potency and specificity, lack of toxicity, bioavailability and duration of
      action. Discovering a compound with these properties is invariably an
      evolutionary process. Fragment based drug discovery sets out to identify a
      starting compound by screening a library of small molecules representing
      fragments which cover the chemical space of drug like matter. Fragment based
      screening is increasingly used in the pharmaceutical industry in the early stages
      of lead identification and optimization. We will provide an introduction into
      this approach and discuss a number of examples which show how fragment based drug
      discovery has been used in the discovery of starting points for drug discovery
      programs and in their optimization.

PMID- 19601889
TI  - Antimicrobial development in the era of emerging resistance.
AB  - Antibiotics currently under study by the Food and Drugs Administration include:
      faropenem (for treatment of sinusitis, bronchitis, and community-acquired
      pneumonia), dalbavancin (for catheter infections), telavancin (for treatment of
      nosocomial pneumonia), oritavancin (for bacteremia), ceftobiprole and iclaprim
      (for pneumonias). Moreover, all of them would be useful for skin and soft tissue
      infections.

PMID- 19601890
TI  - A new strategy to destroy antibiotic resistant microorganisms: antimicrobial
      photodynamic treatment.
AB  - Photodynamic activity of chemical compounds towards microorganisms was first
      published at the turn of 20th century and it is based on the concept that a
      chemical compound, known as the photosensitizer, is localized preferentially in
      the microorganism and subsequently activated by low doses of visible light of an
      appropriate wavelength to generate reactive oxygen species that are toxic to the
      target microorganisms. Processes, in which absorption of light by a
      photosensitizer induces chemical changes in another molecule, are defined as
      photosensitizing reactions. Since the middle of the last century, antibacterial
      photosensitizing reactions were forgotten because of the discovery and the
      beginning of the Golden Age of antibiotics. Certainly, in the last decades the
      worldwide rise in antibiotic resistance has driven research to the development of
      new anti-microbial strategies. Different classes of molecules including
      phenothiazine, porphyrines, phthalocyanines, and fullerenes have demonstrated
      antimicrobial efficacy against a broad spectrum of antibiotic resistant
      microorganisms upon illumination. Due to their extended pi-conjugated system
      these molecules absorb visible light, have a high triplet quantum yield and can
      generate reactive oxygen species upon illumination. This mini-review will focus
      on some major advances regarding physical and chemical properties of
      photosensitizers and light sources that appear to be suitable in the field of
      antimicrobial photodynamic therapy. Currently, topical application of a
      photosensitizer on infected tissues and subsequent illumination seems to be the
      most promising feature of antimicrobial photodynamic therapy, thereby not harming
      the surrounding tissue or disturbing the residual bacteria-flora of the tissue.

PMID- 19601892
TI  - Involvement of MAPK signalling in human villous trophoblast differentiation.
AB  - Human villous trophoblast differentiation is a complex and highly regulated
      process essential for the well-being of the pregnancy and fetal development. In
      this review, we present an overview of the role of MAPKs signalling in
      morphological and functional differentiation of villous trophoblast.

PMID- 19601893
TI  - Structural and physicochemical profiling of morphine and related compounds of
      therapeutic interest.
AB  - A concise account of the physicochemical properties of morphine and its
      derivatives of therapeutic interest is provided. Such properties include
      macroscopic and microscopic acid/base parameters, lipophilicity, solubility,
      permeability that all influence the fate of drugs in the body. The dependence of
      these parameters on pH is discussed and subsequent implications in drug
      administration and formulation are presented.

PMID- 19601894
TI  - Antiviral properties of glycyrrhizic acid and its semisynthetic derivatives.
AB  - Some natural triterpenes exert a definite antiviral activity on several human
      viruses. New synthetic derivatives of glycyrrhizic acid (GL) are even more active
      than the parental molecule. GL can alter the expression of viral genes involved
      in cell transformation, thus opening a new window for speculating on viral
      cancerogenesis.

PMID- 19601895
TI  - ABAD: a potential therapeutic target for Abeta-induced mitochondrial dysfunction
      in Alzheimer's disease.
AB  - Amyloid-beta-peptide (Abetabinding to mitochondrial Abeta-binding alcohol
      dehydrogenase (ABAD) enzyme triggers a series of events leading to mitochondrial
      dysfunction characteristic of Alzheimer's disease (AD). Thus this interaction may
      represent a novel target for treatment strategy against AD. In this review we
      summarize current findings regarding the ABAD-Abeta interaction, namely
      structural and biophysical data, available inhibitors and more recent data from
      proteomic studies.

PMID- 19601896
TI  - Cellular efflux of cAMP and cGMP - a question about selectivity.
AB  - The present paper reviews and discusses selectivity of ABCC4 (MRP4), ABCC5 (MRP5)
      and ABCC11 (MRP8) as cellular efflux pumps for cAMP and cGMP. These transporters
      are potential drug targets for selective modulation of cyclic nucleotide action.

PMID- 19601898
TI  - Editorial: Developments in membrane fusion.

PMID- 19601897
TI  - Sulfanyltriazole/tetrazoles: a promising class of HIV-1 NNRTIs.
AB  - There is an urgent need for the design and development of new and safer drugs for
      the treatment of human immunodeficiency virus (HIV) infection, specifically
      active against drug-resistant viral strains. Recently, sulfanyltriazole/tetrazole
      derivatives were reported as potent HIV-1 non-nucleoside reverse transcriptase
      inhibitors (NNRTIs), with low nanomolar intrinsic activity against RT and
      submicromolar antiviral activity in HIV infected cells. In this review, the
      structural modifications, SAR analysis and docking studies of
      sulfanyltriazole/tetrazoles HIV-1 NNRTIs are discussed, and other interesting
      NNRTIs with the same or similar pharmacophore as the sulfanyltriazole/tetrazole
      derivatives are also presented and analyzed for their in SAR.

PMID- 19601899
TI  - Membrane fusion: role of SNAREs and calcium.
AB  - Life processes are governed at the chemical level, and therefore knowledge of how
      single molecules interact, provides a fundamental understanding of nature. The
      molecular mechanism of membrane fusion essential to vital cellular activities
      such as intracellular transport, hormone secretion, enzyme release, or
      neurotransmission, involve the assembly and disassembly of a specialized set of
      proteins present in opposing bilayers. Target membrane proteins at the cell
      plasma membrane SNAP-25 and syntaxin termed t-SNAREs, and secretory vesicle
      associated protein VAMP or v-SNARE, are part of the conserved protein complex
      involved in fusion of opposing membranes. It has been demonstrated that in the
      presence of Ca2+, t-SNAREs and v-SNARE in opposing bilayers interact and self
      assemble in a circular pattern, to form conducting channels. Such self-assembly
      of t-/v-SNAREs in a ring conformation occurs only when the respective SNAREs are
      in association with membrane. X-ray diffraction measurements further demonstrate
      that t-SNAREs in the target membrane and v-SNARE in the vesicle membrane overcome
      repulsive forces to bring opposing membranes close to within a distance of 2.8 A.
      Studies suggest that calcium bridging of the opposing bilayers, lead to release
      of water from hydrated Ca2+ ions as well as the loosely coordinated water at PO
      lipid head groups, leading to membrane destabilization and fusion. The t-/v-SNARE
      is a tight complex, who's disassembly requires an ATPase called NSF, which
      functions as a right-handed molecular motor.

PMID- 19601901
TI  - Characterization of peptide-induced morphological alterations in membranes by
      fluorescence resonance energy transfer.
AB  - Interaction of fusogenic or membrane-perturbing peptides with lipid bilayers
      often involves drastic rearrangements of the membrane structure, with
      redistribution of lipids, inducement of bilayer curvature, or formation of non
      bilayer or multibilayer structures. Fluorescence (or Forster) Resonance Energy
      Transfer (FRET) is a photophysical technique which has an acute sensitivity to
      distances in the nanometer range, and, as such, is particularly suited to probe
      alterations in membrane organization in this length scale. This article reviews
      methods and selected applications of FRET in this field, from the now classic
      (fusion induced) lipid-mixing assay to examples where kinetic modeling of FRET
      enables the recovery of topological information.

PMID- 19601900
TI  - The "Tilted Peptide Theory" links membrane insertion properties and fusogenicity
      of viral fusion peptides.
AB  - Class I fusion glycoproteins of viruses are involved in the fusion between viral
      envelope and cell membrane. A region located in the N-terminal domain of these
      glycoproteins, called the fusion peptide, is essential for fusion. Fusion
      peptides are able to induce by themselves in vitro membrane fusion. In this
      paper, we review the properties of those peptides related to their fusogenicity,
      in particular the correlation existing between their ability to insert obliquely
      in membranes and fusogenicity. This relation notably allows predicting
      successfully the minimal region of some fusion peptides sufficient to induce
      significant in vitro fusion. The notion of obliquity and fusogenicity is
      discussed in terms of the existing proposed mechanisms for viral fusion.

PMID- 19601902
TI  - Membrane permeabilization by multivalent anti-microbial peptides.
AB  - Antimicrobial peptides (AMP's) are promising compounds in the battle against
      antibiotic resistant pathogens. Many AMP's function by interacting with the
      bacterial membrane and selectively permeabilizing it. Improvements are desired in
      the potency and the in vivo stability of the AMP's. Both aspects have been
      approached by the preparation of multivalent versions of AMP's that contain
      several copies of the peptide attached to a scaffold or core molecule. Both short
      and long sequences have been used and in selected cases major increases in
      antibacterial activity, membrane permeabilization potency and in vivo stability
      have been obtained.

PMID- 19601903
TI  - Antimicrobial peptides and viral fusion peptides: how different they are?
AB  - Similarly to antimicrobial peptides (AMPs), viral fusion peptides (FPs) are
      membrane-active peptides. This minireview emphasizes the common properties of
      AMPs and FPs with a special focus on the intrinsic flexibility and structural
      adaptability of these peptides that are responsible for different mode of
      interaction with the membrane bilayers. The potential use of AMPs as
      multifunctional drugs with both antibacterial and antiviral properties is
      discussed.

PMID- 19601904
TI  - Membrane fusion and fission: enveloped viruses.
AB  - Membrane fusion and fission are two key processes that occur during the
      replication of enveloped viruses, namely access to the interior of the host-cell
      (entry, which requires fusion of the viral envelope with the target cell
      envelope) and dissemination of viral progeny after replication (egress, which
      involves budding and fission). These dynamic processes are mediated by
      specialized proteins that modify and bend the lipid bilayer transiently and
      locally. This review focuses on fusion and fission reactions and on the
      hypothetical shared mechanism that generates their driving force.

PMID- 19601905
TI  - The role of glycoprotein H in herpesvirus membrane fusion.
AB  - The mechanism by which herpesviruses fuse with cellular membranes to permit virus
      entry is still relatively poorly understood. This process is proving difficult to
      unravel, largely due to the fact that multiple viral envelope proteins appear to
      function in concert to mediate the fusion event. For Herpes Simplex Virus Type 1
      (HSV1), glycoproteins B, D and the gHL heterodimer are all required for fusion,
      and gHL counterparts are involved in the fusion process of all other members of
      the herpesvirus family. An understanding of the functional domains of gH that are
      critical for fusion may offer the possibility of designing specific peptide
      inhibitors of virus entry, and recent progress has highlighted the potential
      usefulness of this approach. This review discusses these advances and outlines
      some of the similarities and differences between gH homologues of the different
      members of this diverse family of viruses.

PMID- 19601906
TI  - Composition and functions of the influenza fusion peptide.
AB  - Fusion of the influenza virus envelope with the endosomal membrane of host cells
      is mediated by the hemagglutinin glycoprotein (HA). The most conserved region of
      HA is at the N-terminus of the HA2 subunit, a relatively hydrophobic sequence of
      amino acids referred to as the fusion peptide. This domain is critical both for
      setting the trigger for fusion and for destabilizing target membranes during the
      fusion process. The "trigger" is set by cleavage of the HA precursor polypeptide,
      when the newly-generated HA2 N-terminal fusion peptide positions itself into the
      trimer interior and makes contacts with ionizable residues to generate a fusion
      competent neutral pH structure. This essentially "primes" the HA such that
      subsequent acidification of the endosomal environment can induce the irreversible
      conformational changes that result in membrane fusion. A key component of these
      acid-induced structural rearrangements involves the extrusion of the fusion
      peptide from its buried position and its relocation to interact with the target
      membrane. The role of the fusion peptide for both priming the neutral pH
      structure and interacting with cellular membranes during the fusion process is
      discussed.

PMID- 19601907
TI  - Viral inactivation based on inhibition of membrane fusion: understanding the role
      of histidine protonation to develop new viral vaccines.
AB  - Membrane fusion is an essential step in the entry of enveloped viruses into their
      host cells, what makes it a potentially attractive target for viral inactivation
      approaches. Fusion is mediated by viral surface glycoproteins that undergo
      conformational changes triggered by interaction with specific cellular receptors
      or by the exposition to low pH of endossomal medium. Here we review how several
      studies on the structural rearrangements of vesicular stomatitis virus (VSV)
      glycoprotein G during cellular recognition and fusion led us to propose a crucial
      role of the protonation of His residues for G protein activity. Moreover, we
      demonstrated that using diethylpyrocarbonate (DEPC), a histidine-modifying
      compound, it was possible to abolish viral infectivity and pathogenicity in mice,
      and to elicit neutralizing antibodies that confer protection in these animals
      against challenge using lethal doses of the virus. The presence of conserved His
      residues in a wide range of viral fusion proteins and the use of DEPC as a more
      general means for vaccine development will be also discussed.

PMID- 19601908
TI  - Inhibition of viral-induced membrane fusion by peptides.
AB  - Enveloped animal viruses fuse their membrane with a host cell membrane in order
      to deliver their genome into the cytoplasm of the cell and thus initiating
      infection. This crucial step is mediated by virally encoded transmembrane
      proteins that, following an appropriate triggering, insert their fusion peptides
      into the target membrane and, through a cascade of conformational changes, drive
      the merging of the two apposing membranes. The battle against viruses is ongoing
      with the constant threat of viruses developing resistance to present drugs and
      emerging viruses, therefore there is a continuous challenge to improve our
      defence strategies. Entry inhibitors are currently in development for diverse
      human and animal viral pathogens, and advances in our understanding on how viral
      entry proteins undergo conformational changes that lead to entry offer a huge
      potential for the development of novel therapeutics. This review describes recent
      advances on viral-mediated fusion mechanisms concentrating on the development of
      peptidic inhibitors of membrane fusion.

PMID- 19601909
TI  - Describing evolution of hemagglutinins from influenza A viruses using a
      differential equation.
AB  - Since 1999 we have developed three approaches to quantifying each amino acid in a
      protein as well as a protein in whole based on random mechanisms. With our
      approaches, we can reliably describe the evolution of a protein family, for
      example, the hemagglutinins from influenza A viruses along the time course in a 2
      dimensional graph, and then we use the fast Fourier transform to find the
      mutation periodicity in order to time the mutation. In this study, we realize
      that the changes in quantified randomness in a hemagglutinin family over time is
      the difference between randomness associated with mutant amino acids and
      randomness associated with original amino acids. This is a standard mass-balance
      relationship, by which we can build a differential equation for a hemagglutinin
      family or a system of differential equations for all hemagglutinins in the
      family. In this context, the randomness defined by us actually is the entropy,
      thus we have a general model to describe the evolution, namely, the evolution is
      the exchange of entropy between protein family and environment through mutations
      quantified using our approaches.

PMID- 19601910
TI  - The use of tripeptides for lead discovery of 5-HT4 receptor ligands.
AB  - A series of 30 tripeptides were synthesized and tested as novel 5-HT4 receptor
      ligands. Receptor binding assays showed that a subset of compounds had reasonable
      potency relative to the agonists serotonin and 5-methoxytryptamine. Structure
      activity analyses and molecular docking have highlighted avenues for further
      synthetic work.

PMID- 19601911
TI  - Efficient manual Fmoc solid-phase synthesis of the N-terminal segment of
      surfactant protein B (SP-B(1-25)).
AB  - The N-terminal 25 residue segment of human surfactant protein B (SP-B(1-25)) was
      synthesised in 26% yield by manual Fmoc solid-phase peptide synthesis (Fmoc SPPS)
      using low-loading Fmoc-Gly-Wang resin. Substantial oxidation of Met(21) occurred
      during the synthesis, and the addition of Bu(4)NBr to a TFA/water/EDT/TIS
      cleavage cocktail enabled facile reduction of Met(O)(21)-SP-B(1-25) to SP-B(1
      25). The methods described herein are generally applicable to the Fmoc SPPS of
      difficult sequences containing methionine.

PMID- 19601913
TI  - Improving the classification of nuclear receptors with feature selection.
AB  - Nuclear receptors are involved in multiple cellular signaling pathways that
      affect and regulate processes. Because of their physiology and pathophysiology
      significance, classification of nuclear receptors is essential for the proper
      understanding of their functions. Bhasin and Raghava have shown that the
      subfamilies of nuclear receptors are closely correlated with their amino acid
      composition and dipeptide composition [29]. They characterized each protein by a
      400 dimensional feature vector. However, using high dimensional feature vectors
      for characterization of protein sequences will increase the computational cost as
      well as the risk of overfitting. Therefore, using only those features that are
      most relevant to the present task might improve the prediction system, and might
      also provide us with some biologically useful knowledge. In this paper a feature
      selection approach was proposed to identify relevant features and a prediction
      engine of support vector machines was developed to estimate the prediction
      accuracy of classification using the selected features. A reduced subset
      containing 30 features was accepted to characterize the protein sequences in view
      of its good discriminative power towards the classes, in which 18 are of amino
      acid composition and 12 are of dipeptide composition. This reduced feature subset
      resulted in an overall accuracy of 98.9% in a 5-fold cross-validation test,
      higher than 88.7% of amino acid composition based method and almost as high as
      99.3% of dipeptide composition based method. Moreover, an overall accuracy of
      93.7% was reached when it was evaluated on a blind data set of 63 nuclear
      receptors. On the other hand, an overall accuracy of 96.1% and 95.2% based on the
      reduced 12 dipeptide compositions was observed simultaneously in the 5-fold cross
      validation test and the blind data set test, respectively. These results
      demonstrate the effectiveness of the present method.

PMID- 19601912
TI  - Conservation of hydrophobicity within viral envelope glycoproteins reveals a
      putative hepatitis C virus fusion peptide.
AB  - The mechanism(s) by which hepatitis C virus (HCV) enters and infects cells
      remains unknown. Identifying the HCV fusion peptide(s) and understanding the
      early stages of infection may provide new opportunities for improved antiviral
      therapy. The HCV envelope glycoprotein E2 is thought to be a class II fusion
      protein. Class II fusion proteins are exemplified by the E protein of the tick
      borne encephalitis virus (TBEV) and the E1 protein of the Semliki Forest virus
      (SFV). Analysis of the hydrophobicity profiles of four HCV E2 envelope
      glycoproteins revealed a region with a conserved three-pronged pattern of
      hydrophobicity, termed the tridentate (TD) region. The primary sequence of the TD
      region is highly conserved in all 490 HCV strains currently reported. The known
      fusion peptide loops of TBEV and SFV share the characteristic TD region
      hydrophobicity profile and significant sequence conservation in the TD region was
      identified in the E and E1 glycoproteins of members of the Flaviviridae and
      Togaviridae families, respectively. The HCV TD region peptides have
      membranotropic activity; in molecular dynamics (MD) simulations, the HCV TD
      region peptides insert into in a biomimetic bilayer in a similar manner to the
      TBEV fusion peptide and the peptides induce effective mixing of lipid membranes
      in a liposome fusion assay. Together these results indicate that the highly
      conserved TD region of the HCV E2 protein is a fusion peptide candidate and may
      be an important factor in the class II fusion mechanism.

PMID- 19601914
TI  - Plasma ghrelin levels in patients with Familial Mediterranean Fever.
AB  - Familial mediterranean fever (FMF) is a familial disease characterized by
      recurrent episodes of febrile serositis, peritonitis, arthritis and pleuritis.
      Many studies have been performed is an attempt to understand the basis of the
      inflammatory attacts in FMF. Ghrelin, a recently described orexigene peptide is
      predominantly produced by stomach. Ghrelin also exerts multiple regulatory
      effects on immune system. It has reported that grelin has anti-inflammatory
      effects. There is currently no published evidence demonstrating a role for anti
      inflammatory effects of ghrelin in FMF. For this reason, we investigated the role
      of plasma ghrelin levels in patients with FMF. Thirty seven patients with FMF and
      10 healthy controls (5 female, 5 male; mean age 35.4 +/- 5.6 years) were enrolled
      in this study. Twenty-one patients were in active stage (10 female, 11 male, mean
      age; 31.0 +/- 5.4 years, mean disease duration 7.2 +/- 3.3 years) and 16 patients
      were in inactive stage (7 female,9 male, mean age; 33.0 +/- 6.0 years, mean
      disease duration; 8.7 +/- 3.2 years). Plasma ghrelin levels were determined by
      EIA. The mean plasma ghrelin levels were 158.4 +/- 52.9 pg/ml in patients with
      FMF and 56.7 +/- 7.5 pg/ml in healthy controls. The mean plasma ghrelin levels
      were 190.5 +/- 49.4 pg/ml in the active patients and 116.2 +/- 11.7 pg/ml in the
      inactive patients. Plasma ghrelin levels were significantly high in patients with
      FMF compared to healthy controls (p<0.001). Plasma ghrelin levels were
      significantly high in the active patients compared to in the inactive patients
      and healthy controls (p<0.001 and p<0.001 respectively). There was significantly
      difference between in active and inactive patients with FMF (p<0.001). As a
      results; Plasma ghrelin levels were high both in active and inactive patients
      with FMF. It is showed that ghrelin may play significant role of the pathogenesis
      of FMF.

PMID- 19601915
TI  - Investigation of folding of purified recombinant GRA1 protein using web based
      protein disorder servers and trypsin digestion.
AB  - The successful folding of a recombinant protein after expression and purification
      is essential for structural, biochemical and vaccination studies. Toxoplasma
      gondii recombinant GRA1 protein is a promising vaccine candidate against
      toxoplasmosis. In the present study, the folding of recombinant GRA1 protein has
      been evaluated by web based bioinformatics tools that predict protein folding.
      Subsequently, trypsin digestion, which is a simple indication of proper protein
      folding, has been used to determine whether recombinant GRA1 protein is likely to
      be folded. The results indicate that the recombinant GRA1 protein is predicted to
      be folded by most of the web based bioinformatics predictors. Moreover, in
      protease digestion experiments, the recombinant GRA1, which was purified to
      homogeneity without the use of denaturants, gives rise to a discrete band pattern
      that is indicative of a folded protein. Together, the results suggest that
      recombinant GRA1 protein is in a folded conformation, suitable for structural,
      biochemical and vaccination studies.

PMID- 19601916
TI  - Polytope DNA vaccine development against hepatitis C virus: a streamlined
      approach from in silico design to in vitro and primary in vivo analyses in BALB/c
      mice.
AB  - For chronic viral infections like Hepatitis C, CD8-CTLs have emerged as important
      protective tools. Hence, isolated dominant epitopes arranged as polytope DNA or
      peptide vaccines represent a promising approach. However, because of
      controversial rules governing the polytope construction and epitope processing,
      proper design and primary analysis of such vaccines are prior to the costly
      transgenic animal studies. In this study, based on in silico epitope selection,
      four HLA-A2 (C132, E614 and N1406) and H-2d (E405 and C132) immunodominant CD8
      epitopes of HCV were selected. The codon optimized nucleotide sequences of the
      epitopes were assembled by overlap extension PCR in three different sequential
      tandems for the best proteasomal cleavage predictions and cloned into pcDNA3.1
      vector. In addition, to enhance particulate formation, three other plasmids
      containing the fusion of polytopes with hepatitis B surface antigen gene (HBsAg)
      were also constructed. Proper expression of all constructs in transfected Cos-7
      cells was verified by RT-PCR, immunofluorescence, Western-blot, ELISA and dot
      blot techniques. Moreover, particle formation of HBsAg-fused polytopes was
      manifested by their secretion to the culture media albeit in lesser amounts
      compared to sole HBsAg protein. Finally, the positive delayed-type
      hypersensitivity (DTH) response of vaccinated mice indicated the in vivo
      expression of all constructs and efficient stimulation of immune response, which
      was stronger for HBsAg fusion constructs. In addition, proper processing of the
      epitopes was evidenced by the DTH response towards H-2d epitopic peptides. These
      data provide enough support and merit for the further evaluation of the designed
      constructs in HLA-A2 transgenic mice.

PMID- 19601917
TI  - Synergistic activation of leukocytes by bacterial chemoattractants: potential
      drug targets.
AB  - Accumulating evidence demonstrates that bacterial chemoattractants not only
      attract leukocytes (chemotaxis) but also contribute directly to inflammation by
      activation of leukocytes to produce a variety of pro-inflammatory cytokines.
      Recent studies have shown that mixtures of the bacterial chemoattractant fMLP (N
      formyl-Met-Leu-Phe) and other bacterial products/components such as LPS
      (lipopolysaccharide) behave synergistically in activating leukocytes. These
      results suggest that inflammatory responses are induced by multiple inducers that
      operate synergistically through multiple signaling pathways. This synergy is
      likely to play a significant role in the induction of host defense to bacterial
      infections and in the pathogenesis of inflammatory disorders. These results also
      demonstrate that the control of inflammation is likely best understood at the
      level of synergistic regulation of intracellular signaling. The use of
      pharmacological inhibitors to modulate synergistic molecules is therefore an
      attractive possibility for the treatment of inflammatory disease. In this review,
      we will provide a brief summary of recent studies on the regulation of leukocyte
      functioning by bacterial chemoattractants.

PMID- 19601918
TI  - A current update on the use of alpha lipoic acid in the management of type 2
      diabetes mellitus.
AB  - Type 2 Diabetes Mellitus (T2DM) which is characterised by insulin resistance, is
      closely linked to the triad of glucolipotoxicity, inflammation and oxidative
      stress. Increased adiposity, leading to increased free fatty acids (FFAs),
      contributes to insulin resistance by disrupting the signal transduction pathway
      of insulin mediated glucose disposal, and causes impaired insulin secretion.
      Hyperglycaemia and dyslipidaemia driven oxidative stress resulting from enhanced
      free-radical formation and/or defects in antioxidant defence is implicated in the
      pathogenesis of diabetic neuropathy (DN). This and other inflammatory pathways
      account for a complex network of interacting metabolic factors responsible for
      causing diabetes and her complications. There is growing evidence that Alpha
      Lipoic Acid (ALA) has beneficial effects on the treatment of T2DM and some of its
      complications. It represents an attractive pharmacological target in the
      treatment of T2DM by modulating the signal transduction pathways in insulin
      resistance and antagonizing the oxidative and inflammatory stresses, which are
      major players in the pathogenesis of this disorder. A potent anti-oxidant and
      free radical scavenger, ALA also targets cellular signal transduction pathways
      which increases glucose uptake and utilization, thus providing specific targeted
      therapy in the treatment of insulin resistance and diabetic neuropathy. Apart
      from the rare risk of Insulin Autoimmune Syndrome (IAS), ALA has shown to be
      relatively safe, even in patients with renal and liver failure. This review
      focuses and summarises the molecular mechanisms of T2DM, and underlines the
      therapeutic value of ALA in this globally significant disease.

PMID- 19601919
TI  - Stem cell patents: an innovative approach to anti-cancer drug discovery.
AB  - Over the last decade, improvements in cancer therapies have prolonged the lives
      of cancer patients. Despite dramatic advances in imaging technology, surgical
      techniques, and adjuvant radio- and chemotherapy, the overall prognosis of this
      disease remains dismal. In light of this, there is an urgent need for the
      development of more effective therapies that can target residual disseminated
      tumor burden. Given the heterogeneity of tumors in general, no one strategy is
      likely to provide a satisfactory treatment regimen. Until the middle of the 20th
      century, medical treatments were limited to options like drugs, surgery,
      antibiotics, and radiation, but in the last years stem cells, due to their
      pathotropism, have become particularly attractive candidates not only to replace
      damaged tissue in degenerative pathologies, but also to deliver therapeutic
      molecules in patients with disseminated metastatic cancer. Worldwide there have
      been over 2000 patent applications involving human and non-human stem cells, of
      which one quarter refer to embryonic stem cells. Over one third of all stem cell
      applications and one quarter of all embryonic stem cell applications have been
      granted. The aim of this review is primarily to focus on the recent development
      of stem cell patents in cancer treatments.

PMID- 19601920
TI  - Anti-angiogenic therapy in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is one of the most common cancers in the United
      States. Recent achievements in translational research have lead to significant
      developments in treatment strategies for this malignancy. RCC is a richly
      vascular neoplasm. A better understanding of its biology has helped in the
      development of antiangiogenic therapy. Vascular endothelial growth factor (VEGF)
      is the most important molecular target in the treatment of RCC. Patents have been
      filed for anti-VEGF and other molecular pathways involved in the pathogenesis of
      RCC.

PMID- 19601921
TI  - Endovascular repair of thoracic aortic aneurysms.
AB  - A thoracic aortic aneurysm is a potentially life-threatening condition that
      involves a structural weakness of the aortic wall, which can lead to aneurysm,
      rupture, or dissection. Optimal treatment strategies for lesions of the thoracic
      aorta are still controversial. Open surgery is complex and is associated with
      significant morbidity and mortality. Endovascular stenting has emerged as an
      alternative to open repair in patients requiring surgery for thoracic aortic
      pathology. Endovascular treatment of vascular disease involving the descending
      thoracic aorta can be performed safely. It is an alternative option to open
      repair, less invasive, and carries a relatively low risk. Due to the low
      morbidity and mortality of endovascular repair, this option has become attractive
      to many surgeons lately. Stent grafting has become the first-line approach to
      traumatic thoracic aortic transections in some trauma centers. However, the
      challenges of accurate placement within an angulated arch, size of the delivery
      system, and uncertainty regarding long-term durability have been cited as reasons
      for caution. Major challenges are the technical aspects of the procedure and the
      learning curve to handle the delivery system and the variability in the anatomy
      of the aorta. The goal of this article is to review endovascular repair of the
      thoracic aorta in the current literature outlining some recent patents.

PMID- 19601922
TI  - Microbubbles as drug delivery systems in cerebrovascular diseases.
AB  - The field of neurovascular ultrasound is growing rapidly with new applications.
      While ultrasound contrast agents were initially used to overcome poor
      transcranial bone windows for identification of cerebral arteries, newgeneration
      microbubbles in combination with innovative contrast-specific ultrasound
      techniques now enable potential therapeutic procedures. This article will provide
      a review of recent and emerging developments along with patents in ultrasound
      technology and contrast-specific therapeutic techniques for cerebrovascular
      patients.

PMID- 19601923
TI  - Expression sequence tag and QTL/MAS of goat/sheep in China.
AB  - Goats/sheep are important in the animal agriculture of China. Distribution of
      these animals in China is closely related to the economic performance and
      ecological conditions in the specific regions. Comparative genome study is
      popular in China although the sheep and goat genome information are not well
      sequenced. Expression Sequence Tags (EST) are well developed in skin and ovary
      organ. Transgenic productions are focused on goat milk chiefly. Microsatellite
      DNA and mtDNA polymorphism were used to analyze the genetic structure mainly and
      some of them were used to detect the Quantitative Trait Loci(QTL) of goat and
      sheep. Only the candidate gene markers are used as Marker Assisted Selection
      (MAS) and integrated into Best Linear Unbiased Prediction (BLUP) selection
      strategy in goat and sheep nucleus breeding flock according to different breeds.
      Although some studies have proposed direct selection on the individual gene loci
      responsible for the genetic variation in some traits, there are 20 goat/sheep
      gene patents in the past decade. Some patents on gene with extremely broad claims
      will shadow over the commercialization of these gene and fill the blank of the
      gene patents in goat/sheep fields.

PMID- 19601924
TI  - Recent patents on PCSK9: a new target for treating hypercholesterolemia.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9), the ninth member of the
      proprotein convertase (PC)family, has emerged as a potential target for reducing
      plasma low-density lipoprotein cholesterol (LDL-c) levels. PCSK9post
      transcriptionally downregulates the low-density lipoprotein receptor (LDLR) in
      the liver by binding to the epidermalgrowth factor-like repeat A (EGF-A) domain
      of the LDLR and thereby controls the level of LDL-c in plasma. Some of its
      natural mutations called gain-of-function mutations cause hypercholesterolemia
      and coronary heart disease (CHD), whereas loss-of-function mutations in the PCSK9
      gene are associated with hypocholesterolemia. This review summarizes the current
      understanding of PCSK9 and recently published patent and patent applications on
      methods and techniques that may efficiently reduce plasma LDL-c levels through
      inhibiting PCSK9 expression by antisense oligonucleotides, small interference
      RNAs (siRNAs), specific antibodies, or other small molecules.

PMID- 19601927
TI  - Homocysteine and stroke: another brick in the wall.
AB  - After a long debate, due to conflicting data from clinical studies, homocysteine
      is now largely accepted as a risk factor for cardiovascular diseases including
      stroke. To date, the role of elevated homocysteine levels in stroke recurrences
      has not been evaluated. In the present issue of Clinical Science, Zhang and co
      workers prove that Chinese patients with high homocysteine levels have an
      increased risk of stroke recurrence and of all-cause mortality with respect to
      patients with lower levels. Remarkably, in their study, high homocysteine levels
      were associated with an increased risk of stroke recurrence for atherothrombotic
      stroke and intracerebral haemorrhage, but not lacunar stroke. The study by Zhang
      and co-workers provides important information for clinical practice and
      represents the basis for further investigations, as it raises questions referring
      to the puzzling relationship between homocysteine and cardiovascular disease.
      Moreover, the results support the hypothesis that, for undisclosed reasons, the
      relationship between homocysteine and cardiovascular disease may not be
      homogeneous for all the conditions encompassed in the category of cardiovascular
      disease, being peculiar for stroke patients. The finding of an association
      between high homocysteine levels and a risk of recurrent stroke or all-cause
      mortality in patients with intracerebral haemorrhage should be taken with caution
      until this same result is confirmed in other case series with different
      ethnicity.

PMID- 19601928
TI  - EDHF: an update.
AB  - The endothelium controls vascular tone not only by releasing NO and prostacyclin,
      but also by other pathways causing hyperpolarization of the underlying smooth
      muscle cells. This characteristic was at the origin of the term 'endothelium
      derived hyperpolarizing factor' (EDHF). However, this acronym includes different
      mechanisms. Arachidonic acid metabolites derived from the cyclo-oxygenases,
      lipoxygenases and cytochrome P450 pathways, H(2)O(2), CO, H(2)S and various
      peptides can be released by endothelial cells. These factors activate different
      families of K(+) channels and hyperpolarization of the vascular smooth muscle
      cells contribute to the mechanisms leading to their relaxation. Additionally,
      another pathway associated with the hyperpolarization of both endothelial and
      vascular smooth muscle cells contributes also to endothelium-dependent
      relaxations (EDHF-mediated responses). These responses involve an increase in the
      intracellular Ca(2+) concentration of the endothelial cells, followed by the
      opening of SK(Ca) and IK(Ca) channels (small and intermediate conductance Ca(2+)
      activated K(+) channels respectively). These channels have a distinct subcellular
      distribution: SK(Ca) are widely distributed over the plasma membrane, whereas
      IK(Ca) are preferentially expressed in the endothelial projections toward the
      smooth muscle cells. Following SK(Ca) activation, smooth muscle hyperpolarization
      is preferentially evoked by electrical coupling through myoendothelial gap
      junctions, whereas, following IK(Ca) activation, K(+) efflux can activate smooth
      muscle Kir2.1 and/or Na(+)/K(+)-ATPase. EDHF-mediated responses are altered by
      aging and various pathologies. Therapeutic interventions can restore these
      responses, suggesting that the improvement in the EDHF pathway contributes to
      their beneficial effect. A better characterization of EDHF-mediated responses
      should allow the determination of whether or not new drugable targets can be
      identified for the treatment of cardiovascular diseases.

PMID- 19601930
TI  - The metabolic syndrome, testosterone deficiency and erectile dysfunction never
      come alone.

PMID- 19601929
TI  - Structural basis of transport of lysophospholipids by human serum albumin.
AB  - Lysophospholipids play important roles in cellular signal transduction and are
      implicated in many biological processes, including tumorigenesis, angiogenesis,
      immunity, atherosclerosis, arteriosclerosis, cancer and neuronal survival. The
      intracellular transport of lysophospholipids is through FA (fatty acid)-binding
      protein. Lysophospholipids are also found in the extracellular space. However,
      the transport mechanism of lysophospholipids in the extracellular space is
      unknown. HSA (human serum albumin) is the most abundant carrier protein in blood
      plasma and plays an important role in determining the absorption, distribution,
      metabolism and excretion of drugs. In the present study, LPE
      (lysophosphatidylethanolamine) was used as the ligand to analyse the interaction
      of lysophospholipids with HSA by fluorescence quenching and crystallography.
      Fluorescence measurement showed that LPE binds to HSA with a Kd (dissociation
      constant) of 5.6 microM. The presence of FA (myristate) decreases this binding
      affinity (Kd of 12.9 microM). Moreover, we determined the crystal structure of
      HSA in complex with both myristate and LPE and showed that LPE binds at Sudlow
      site I located in subdomain IIA. LPE occupies two of the three subsites in Sudlow
      site I, with the LPE acyl chain occupying the hydrophobic bottom of Sudlow site I
      and the polar head group located at Sudlow site I entrance region pointing to the
      solvent. This orientation of LPE in HSA suggests that HSA is capable of
      accommodating other lysophospholipids and phospholipids. The study provides
      structural information on HSA-lysophospholipid interaction and may facilitate our
      understanding of the transport and distribution of lysophospholipids.

PMID- 19601931
TI  - Human sperm DNA integrity in normal and abnormal semen samples and its
      correlation with sperm characteristics.
AB  - Reports indicate an increase in the incidence of DNA fragmentation in male factor
      infertility and its role in the outcome of assisted reproductive techniques
      (ART). However, reports are conflicting between the relationships of sperm DNA
      integrity with conventional semen parameters. We examined the relationship
      between conventional sperm parameters and DNA integrity using acridine orange
      (AO) test. The study included 373 patients and 28 fertile volunteers. DNA
      normality was compared with semen parameters between the patient and donor
      populations. Significant correlations were noted between DNA normality and sperm
      concentration (r = 0.18, P = 0.000), motility (r = 0.21, P = 0.0001), rapid
      motility (0.19, P = 0.000), normal morphology by World Health Organization (r =
      0.15, P = 0.019) and head defects (r = -0.15, P = 0.023). A significant
      difference was noted in AO levels between donors and patients with
      asthenozoospermia (P = 0.002) and oligoasthenozoospermia (P = 0.001). A
      significant difference in DNA integrity was noted in samples having <30% and >30%
      normal morphology. A wide range of % DNA normality was observed in the patient
      group. Sperm assessment for DNA status using AO is reliable and shows good
      correlation with sperm count, motility and morphology. Assessment of sperm DNA
      status with AO staining may be helpful prior to ART.

PMID- 19601932
TI  - Experimental ischaemia-reperfusion injury induces vascular endothelial growth
      factor expression in the rat testis.
AB  - Testicular torsion causes ischaemia-reperfusion (I-R) injury of testis and might
      lead to male infertility. Its injury initiates a pathophysiological cascade,
      including an activation of inflammatory cytokines and generation of nitric oxide
      and other reactive oxygen species. Vascular endothelial growth factor (VEGF)
      mediates angiogenesis and promotes endothelial cell survival. The aim of our
      study was to investigate the time course expression of VEGF, VEGF-receptor (R)1,
      VEGF-R2, nitric oxide synthases (NOS) in experimental I-R injury of rat testis.
      In torsion side testis, the expression of VEGF protein and mRNA significantly
      increased in a time-dependent manner (P < 0.001 and P < 0.001, respectively).
      Although the expression of VEGF-R1 mRNA was increased in a similar way (P <
      0.001), VEGF-R2 mRNA expression was not detected. In immunohistochemistry, the
      increase in VEGF protein staining was observed in testicular vascular endothelial
      cells and germ cells at 24 h after reperfusion. Significant activation of
      inducible NOS and endothelial NOS was investigated at 12 and 24 h after
      reperfusion (P < 0.01 and P < 0.001, respectively). This is the first report to
      show the time course expression of VEGF in experimental I-R rat testis.

PMID- 19601933
TI  - Effect of long-term administration of zinc after scrotal heating on mice
      spermatozoa and subsequent offspring quality.
AB  - This study was set to investigate whether the adverse effects of heat on
      spermatozoa and subsequent foetuses could be prevented by long-term zinc
      administration. The scrotums of animals were immersed in water at either 43
      degrees C (heat group) or 23 degrees C (control group). Half of the heat and
      control mice were given 10 mg kg(-1) zinc every other day for 60 days and the
      others received sterile saline instead of zinc. Heat stress significantly reduced
      sperm motility, concentration, hypoosmotic swelling-water test (HOS-WT) positive
      and chromomycin A(3) (CMA(3)) negative spermatozoa at the first 15 days, and the
      greatest decrease occurred at 30 days (P < 0.05). Sperm motility, concentration
      and HOS-WT positive spermatozoa were also reduced initially in the zinc
      administered group, but we did not observe any further decrease in the above
      mentioned parameters on day 30 (P < 0.05). The weight of foetuses obtained from
      the females mated with paternal heat treatment males was significantly lower than
      that of the control group (P < 0.05) and long-term zinc therapy caused a partial
      recovery (P > 0.05). This study demonstrates that the adverse effects of
      hyperthermia on semen parameters may be prevented by zinc therapy. Likewise, long
      term administration of zinc could improve quality of litter obtained from the
      females mated with scrotal heat treatment males.

PMID- 19601934
TI  - Effects of date seed oil on testicular antioxidant enzymes and epididymal sperm
      characteristics in male mice.
AB  - The aim of this study was to evaluate the effect of date seed oil (DSO) on
      epididymal sperm characteristics and testicular antioxidant enzymes in male mice.
      DSO was diluted into isotonic saline solution (0.9%) and different doses (5, 10,
      15 and 20%) were prepared. Fifty male mice were divided into five groups; in four
      groups DSO was given by intraperitoneal injection of oil solution for 28 days.
      The control group was injected by isotonic saline solution without DSO. Body and
      reproductive organ weights, sperm characteristics (count, motility, viability and
      morphology) were assessed. In addition, levels of malondialdehyde (MDA),
      activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in
      testes. A significant increase in sperm count, motility and viability of all
      treated animal groups was observed when compared with the control group (P <
      0.05). Unlike, the percentage of abnormal sperm was significantly lower in all
      treated groups than in the control group (P < 0.05). A significant decrease in
      MDA levels and marked increase in SOD and CAT activities in mice treated with
      high doses of DSO (15 and 20%) were also noted. We suggest that DSO can improve
      the epididymal sperm quality and could ameliorate the testicular strategy
      defences.

PMID- 19601936
TI  - Preserved testicular artery at varicocele repair.
AB  - Whether or not varicocele causes infertility is a contentiously debated issue.
      This study aimed to compare semen parameters and pregnancy rate in infertile
      males who underwent varicocelectomy with preserved or accidentally ligated
      testicular artery. Ninety-five infertile oligoasthenozoospermic patients with
      left-sided varicocele were subjected to subinguinal varicocelectomy with trial of
      preserving testicular artery. According to absence or presence of testicular
      artery in the histological excised pedicle the cases were divided into two
      groups; group 1 (n = 60) with preserved testicular artery and group 2 (n = 35)
      where the artery was accidentally ligated being not defined or injured. Semen
      analysis was carried out after 4, 8 and 12 months and post-operative pregnancy
      rate was assessed after 1 year. Serum follicle-stimulating hormone (FSH),
      luteinising hormone (LH) and total testosterone (T) were estimated pre- and post
      operatively. Semen parameters (total sperm count, sperm concentration and sperm
      motility) showed significant increase post-operatively compared with pre
      operative parameters but were comparable in both groups with no significant
      difference. Serum FSH, LH, T hormones and pregnancy rate (23.3% versus 22.9%) 1
      year post-operatively showed no significant difference. It is concluded that
      accidental ligation of testicular artery has no deleterious effect on semen
      parameters during primary varicocele repair if the testicular arterial supply was
      not compromised.

PMID- 19601935
TI  - Examination of the semen quality of patients with uraemia and renal transplant
      recipients in comparison with a control group.
AB  - To examine the semen quality of patients with uraemia and renal transplant
      recipients, 40 patients with uraemia and 40 renal transplant recipients were
      included. According to their interval of post-transplantation, renal transplant
      recipients were subdivided into group A (22) < or =2 years and group B (18) >2
      years. A total of 40 healthy men with normal fertility were included as the
      controls. Semen samples from all subjects were collected and analysed. The
      fertility index (FI) value was calculated. The FI value of the normal fertility
      men was 13.02 (14.26), that of the renal transplant recipient groups A and B were
      5.53 (8.30) and 9.27 (22.49) respectively, while the FI of the patients with
      uraemia was 0.23 (0.76). Compared with the uraemia group, the FI values of renal
      transplant recipient group either group A or group B were significantly better (P
      < 0.01). However, compared with the normal control group, the FI values of renal
      transplant recipient group A were lower (P < 0.01), while there was no
      significant difference between group B and the control group (P > 0.05). In
      conclusion, the FI of renal transplant recipients was recovered close to the
      level of healthy men with normal fertility 2 years after transplantation.

PMID- 19601937
TI  - Controlled freezing studies on boar sperm cryopreservation.
AB  - Boar spermatozoa from different males were frozen at a number of cooling rates
      using a controlled-rate freezing machine designed to minimise thermal variables
      involved in the cooling process, to see whether inter-boar sperm cryosurvival may
      be improved by changing cooling rate. Four cooling rates in the range 3 degrees C
      min(-1) to 24 degrees C min(-1) from +5 degrees C to -5 degrees C and five
      cooling rates in the range 5 degrees C min(-1) to 80 degrees C min(-1) from -5
      degrees C to -80 degrees C were tested. Motile spermatozoa were assessed by CASA,
      plasma membrane integrity by fluorescent probes (SYBR14/propidium iodide) and
      flow cytometry, and acrosome membrane integrity by lectins (PSA-rhodamine) and
      fluorescent microscopy. Cooling rate affected sperm cryosurvival from different
      boars in different ways; that is, spermatozoa from some individuals were less
      susceptible than those from others. For some individuals, sperm cryosurvival was
      poor regardless of cooling rate, but for others it was better with faster rates.
      This confirms cooling rate effects on sperm cryosurvival depend on inter
      individual boar differences more than on the cooling process itself.

PMID- 19601938
TI  - Clinical significance of reactive oxygen species in semen of infertile Indian
      men.
AB  - Reactive oxygen species (ROS) levels in semen are believed to play both
      physiological and pathological roles in male fertility. The study was aimed to
      find the clinical significance of ROS levels in infertile Indian men. This pilot
      study included 33 idiopathic infertile men and 18 proven fertile controls. ROS
      levels in the washed sperm were measured using chemiluminescence assay and
      expressed as 10(6) cpm per 20 million spermatozoa. Sperm count, percent sperm
      motility, and percent normal sperm morphology were found to be significantly (P <
      0.0001) reduced in infertile men compared with the controls. Median (minimum,
      maximum range) ROS levels of the infertile group [24.90 (6.89, 44.71)] were found
      to be significantly (P < 0.0001) elevated compared with the fertile controls
      [0.167(0.15, 2.78)]. No significant correlation was seen between ROS levels and
      semen parameters. Elevated ROS levels in the idiopathic Indian infertile men may
      be one of the underlying reasons for impaired fertility. Therefore measurement of
      seminal ROS levels may be used in Indian infertile men for better understanding
      of the aetiology and selection of antioxidant regimen in the treatment of male
      infertility. However, large studies may be urgently warranted to find out the
      role of antioxidants in ROS elevated Indian infertile men through randomised,
      controlled clinical study.

PMID- 19601939
TI  - Phenotype, hormonal profile and genotype of subjects with partial androgen
      insensitivity syndrome: report of a family with four adult males and one child
      with disorder of sexual differentiation.
AB  - There is little information on the molecular basis of intrafamilial and inter
      familial phenotypic heterogeneity with the same androgen receptor (AR) mutation
      in patients with partial androgen insensitivity syndrome. A genetic analysis was
      performed in a large kindred with ambiguous genitalia and the genotype-phenotype
      correlations were analysed. The index case was brought for sex assignment. Family
      history revealed four other affected members who had hypospadias and varying
      degrees of virilisation. All the affected males had hemizygous mutations in the
      third exon of the AR gene (A596T). One was also found to have a heterozygous
      mutation in the fourth exon of the 5 alpha reductase type 2 gene (G196S). This
      affected male with double mutations was better virilised compared with the other
      affected members with a single mutation. The degree of virilisation correlated
      with serum testosterone levels. Gynaecomastia was not present in any of these
      subjects. It is concluded that the subject with dual gene defects also had higher
      levels of testosterone and pubertal virilsation. Testosterone levels possibly
      govern the degree of pubertal virilisation in subjects with A596T gene defects.
      It is not clear whether the better pubertal virilsation and higher testosterone
      are in any way causally related to the SRD5A2 gene defect.

PMID- 19601940
TI  - Primary anastomosis of the traumatically amputated penis.
AB  - Penile amputation is an uncommon condition for which immediate surgical
      replantation is warranted. This work aimed to represent intervention and
      management for an amputated penis by replantation and reconstruction. A 23-year
      old man presented with traumatic penile amputation for 2 h where the penile
      proximal part was 1 cm far from the pubis. Replantation included end-to-end
      anastomosis of the urethral mucosa over a catheter, approximation of the corpus
      cavernosum and tunica albuginea, anastomosis of the deep dorsal vein, dorsal
      nerve, both dorsal arteries and superficial dorsal vein. At day 5 post
      operatively, the replanted penis had preserved capillary filling. The catheter
      was removed at day 11, where the patient urinated smoothly. The preliminary
      cosmetic appearance was satisfactory with frequent morning erection, reported
      night emission twice within the first month post-operatively. Sensation was
      preserved in the distal anastomosed stump. It is concluded that meticulous
      microsurgical technique decreases the possibility of skin loss and increases the
      chance of erectile function.

PMID- 19601942
TI  - Correlation between quantified breast densities from digital mammography and 18F
      FDG PET uptake.
AB  - To correlate breast density quantified from digital mammograms with mean and
      maximum standardized uptake values (SUVs) from positron emission tomography
      (PET). This was a prospective study that included 56 women with a history of
      suspicion of breast cancer (mean age 49.2 +/- 9.3 years), who underwent 18F
      fluoro-2-deoxyglucose (FDG)-PET imaging of their breasts as well as digital
      mammography. A computer thresholding algorithm was applied to the contralateral
      nonmalignant breasts to quantitatively estimate the breast density on digital
      mammograms. The breasts were also classified into one of four Breast Imaging
      Reporting and Data System categories for density. Comparisons between SUV and
      breast density were made using linear regression and the Student's t-test. Linear
      regression of mean SUV versus average breast density showed a positive
      relationship with a Pearson's correlation coefficient of R(2) = 0.83. The
      quantified breast densities and mean SUVs were significantly greater for
      mammographically dense than nondense breasts (p < 0.0001 for both). The average
      quantified densities and mean SUVs of the breasts were significantly greater for
      premenopausal than postmenopausal patients (p < 0.05). 8/51 (16%) of the patients
      had maximum SUVs that equaled 1.6 or greater. There is a positive linear
      correlation between quantified breast density on digital mammography and FDG
      uptake on PET. Menopausal status affects the metabolic activity of normal breast
      tissue, resulting in higher SUVs in pre- versus postmenopausal patients.

PMID- 19601943
TI  - A novel treatment for postoperative mondor's disease: manual axial distraction.
AB  - Mondor's disease is an uncommon complication of breast and axillary surgery.
      Although self-limiting, the subcutaneous cords may be both painful and
      functionally limiting for the patient. Numerous pharmacologic approaches have
      been tried, but without widespread success, and we wished to evaluate the non
      invasive technique of manual axial distraction in such patients. Thirty
      consecutive patients with axillary Mondor's disease following surgery were
      treated solely with this technique by the senior author (RJS) over a 24-month
      period. Mean age was 45 years (range 32-72) with 27 having undergone formal
      axillary dissection and three sentinel node biopsy. 25 (83.3%) were successfully
      treated with a single procedure, three (10%) with two and two (6.7%) with three
      procedures. we present the initial results of the novel technique of manual axial
      distraction that has been found to be efficacious and without adverse effect. It
      provides a rapid and definitive cure in postoperative Mondor's disease.

PMID- 19601944
TI  - Long-term role of external breast prostheses after total mastectomy.
AB  - After total mastectomy, many women choose to wear external breast prosthesis
      rather than undergo breast reconstruction. The purpose of this study was to
      evaluate long-term satisfaction among external breast prosthesis wearers and the
      impact of satisfaction on prosthesis use. A questionnaire was designed to assess
      demographic information, prosthesis information provision, prosthesis use, and
      satisfaction with prosthesis. Fifty-nine women who had undergone total mastectomy
      without breast reconstruction completed the questionnaire. The majority of women
      (68%) were at least 5 years out from mastectomy. Approximately half (49%) of the
      women had received information about breast prostheses prior to mastectomy; 29%
      received information from the surgeon performing the operation. Frequent and
      prolonged prosthesis use was prevalent with 64% of participants reporting
      prosthesis use all the time, 6-7 days/week. Participants showed high rates (83%)
      of overall satisfaction. However, women who wore their prosthesis out in public
      only were less satisfied than more frequent wearers (50% versus 89%, chi(2) =
      8.83, d.f. = 1, alpha = 0.05). Satisfaction increased over time, as women who
      were greater than 5 years out from mastectomy were more satisfied than women less
      that 5 years post-mastectomy (90% versus 67%, chi(2) = 4.43, d.f. = 1, alpha =
      0.05). The vast majority of women are satisfied with their external breast
      prosthesis several years after mastectomy. Most women used their prosthesis all
      the time and overall satisfaction contributed to higher levels of prosthesis use.
      Given the long-term importance of external breast prostheses for women who have
      undergone mastectomy, a greater effort to inform patients about external breast
      prostheses prior to surgery is needed.

PMID- 19601945
TI  - Toker cells revisited.
AB  - Toker cells are inconspicuous cytokeratin 7 positive cells that should be
      distinguished from intraepidermal involvement by malignant cells seen in Paget's
      disease (PD) of the nipple. The aim of our study was to quantitatively assess the
      number and pattern of distribution of Toker cells in nipples without PD in
      mastectomy specimens. Sequential sections from the nipple of 173 mastectomies
      were evaluated using HE and immunohistochemistry. Two breast pathologists
      reviewed the stains and recorded the number and pattern of distribution of CK7
      positive cells (CK7+) and their HER2/neu, ER and PR status. There were 152/173
      (88.4%) cases with CK7+ cells. The mean number of CK7+ cells per section was 22
      (range 0-200) and the mean number of CK7+ cells per field at 10x was 10 (range 0
      106). 10/37 (27%) of nipples from prophylactic mastectomies and 15/136 (11.1%) of
      mastectomies for cancer displayed over 10 CK7+ cells in an area of 10x. In 32/173
      (18.5%) CK7+ cells formed small groups or clusters. Notably these cells were not
      restricted to the basal part of the epidermis. None of the groups/clusters of
      Toker cells were appreciated on HE stain and all were HER2/neu, ER and PR
      negative. The absence of any CK7+ cells in 20 cases occurred in hyperpigmented
      epidermis, possibly obscuring rare positive cells. Toker cells are frequently
      present in the epidermis of the nipple and are more prevalent than appreciated on
      routine HE stain. These cells can be present in clusters and can have pagetoid
      pattern of distribution. They occur in nipples of cancer patients with or without
      PD and in prophylactic mastectomies performed for high risk patients. The
      substantial number and the clustering of Toker cells should not be mistaken for
      PD of the nipple. Unlike PD, Toker cells have small bland nuclei and are
      characterized by CK7+ and HER2/neu ER and PR negative immunoprofile.

PMID- 19601946
TI  - Primary basaloid carcinoma of the nipple with associated squamous cell carcinoma
      in situ.
AB  - Basaloid carcinomas have been documented in various anatomic locations. We
      describe a primary invasive adenocarcinoma of the nipple with extensive basaloid
      features that was also associated with squamous cell carcinoma (SCC) in situ and
      an aggressive behavior. A 69-year-old woman without a history of breast neoplasia
      presented with right nipple pain. Biopsy of the nipple revealed SCC in situ. One
      year later, she returned with nipple ulceration. An excisional specimen showed a
      1.7 cm nodule composed of invasive sheets and ribbons of basaloid cells with
      numerous mitoses, extensive tumor necrosis and evidence of glandular
      differentiation. SCC in situ was present in the overlying epidermis. The
      differential diagnosis included a primary basaloid adenocarcinoma of the nipple,
      basal cell carcinoma of the nipple, neuroendocrine carcinoma, melanoma, basaloid
      variant of adenoid cystic carcinoma and metastatic disease. Immunohistochemical
      profile of this tumor supported a primary basaloid adenocarcinoma of the nipple.
      Although the initial sentinel lymph node biopsy was negative, within a year of
      diagnosis, the patient developed ipsilateral axillary node and pulmonary
      metastases. To the best of our knowledge, this is the first case of basaloid
      carcinoma to be documented in this anatomic site.

PMID- 19601947
TI  - A case of benign schwannoma of the breast: mammographic, ultrasonographic and
      color Doppler ultrasonographic findings.

PMID- 19601948
TI  - Pigmented mammary Paget's disease presenting as an enlarged areola.

PMID- 19601949
TI  - Primary leiomyosarcoma of the breast.

PMID- 19601950
TI  - Premenopausal breast cancer: estrogen receptor status and insulin-like growth
      factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and
      leptin.

PMID- 19601951
TI  - High proportion of inflammatory breast cancer in the Population-based Cancer
      Registry of Gharbiah, Egypt.

PMID- 19601952
TI  - Intraoperative ultrasound in excision of breast nonpalpable lesions: the
      experience of the breast unit of San Giovanni Hospital in Rome.

PMID- 19601953
TI  - Cross-trial comparison of different AIs.

PMID- 19601954
TI  - Hierarchical partitioning of evolutionary and ecological patterns in the
      organization of phylogenetically-structured species assemblages: application to
      rockfish (genus: Sebastes) in the Southern California Bight.
AB  - Phylogenetic divergences have recently been included in analyses that aim to
      elucidate patterns of biodiversity in space and time. We introduce a generalized
      framework for two widely used phylogenetic diversity (PD) indices: Raos quadratic
      entropy (QE) and Faiths PD. We demonstrate how this framework can be used to
      partition diversity simultaneously across evolutionary periods and spatial (e.g.
      local communities in a region) and / or time units (e.g. a community investigated
      yearly). From a study of rockfish hotspot diversity from the Southern California
      Bight, the analysis of PD revealed a recent decrease in the amount of fish caught
      from six evolutionary deep lineages, with implications for the community
      structure of this speciose group. This approach, which can also be applied to
      trees assembled from functional traits, contributes to our understanding of the
      mechanisms that underpin community organization and to the description of the
      consequences of human-driven impacts in the environment.

PMID- 19601955
TI  - OmpA influences Escherichia coli biofilm formation by repressing cellulose
      production through the CpxRA two-component system.
AB  - Previously we discovered that OmpA of Escherichia coli increases biofilm
      formation on polystyrene surfaces (Gonzalez Barrios et al., Biotechnol Bioeng,
      93:188-200, 2006a). Here we show OmpA influences biofilm formation differently on
      hydrophobic and hydrophilic surfaces since it represses cellulose production
      which is hydrophilic. OmpA increased biofilm formation on polystyrene,
      polypropylene, and polyvinyl surfaces while it decreased biofilm formation on
      glass surfaces. Sand column assays corroborated that OmpA decreases attachment to
      hydrophilic surfaces. The ompA mutant formed sticky colonies, and the
      extracellular polysaccharide that caused stickiness was identified as cellulose.
      A whole-transcriptome study revealed that OmpA induces the CpxRA two-component
      signal transduction pathway that responds to membrane stress. CpxA phosphorylates
      CpxR and results in reduced csgD expression. Reduced CsgD production represses
      adrA expression and results in reduced cellulose production since CsgD and AdrA
      are responsible for 3,5-cyclic diguanylic acid and cellulose synthesis. Real-time
      polymerase chain reaction confirmed csgD and adrA are repressed by OmpA. Biofilm
      and cellulose assays with double deletion mutants adrA ompA, csgB ompA, and cpxR
      ompA confirmed OmpA decreased cellulose production and increased biofilm
      formation on polystyrene surfaces through CpxR and AdrA. Further evidence of the
      link between OmpA and the CpxRA system was that overproduction of OmpA disrupted
      the membrane and led to cell lysis. Therefore, OmpA inhibits cellulose production
      through the CpxRA stress response system, and this reduction in cellulose
      increases biofilm formation on hydrophobic surfaces.

PMID- 19601957
TI  - In situ measurement of methane fluxes and analysis of transcribed particulate
      methane monooxygenase in desert soils.
AB  - Aerated soils are a biological sink for atmospheric methane. However, the
      activity of desert soils and the presence of methanotrophs in these soils have
      hardly been studied. We studied on-site atmospheric methane consumption rates as
      well as the diversity and expression of the pmoA gene, coding for a subunit of
      the particulate methane monooxygenase, in arid and hyperarid soils in the Negev
      Desert, Israel. Methane uptake was only detected in undisturbed soils in the arid
      region (approximately 90 mm year(-1)) and vertical methane profiles in soil
      showed the active layer to be at 0-20 cm depth. No methane uptake was detected in
      the hyperarid soils (approximately 20 mm year(-1)) as well as in disturbed soils
      in the arid region (i.e. agricultural field and a mini-catchment). Molecular
      analysis of the methanotrophic community using terminal restriction fragment
      length polymorphism (T-RFLP) and cloning/sequencing of the pmoA gene detected
      methanotrophs in the active soils, whereas the inactive ones were dominated by
      sequences of the homologous gene amoA, coding for a subunit of the ammonia
      monooxygenase. Even in the active soils, methanotrophs (as well as in situ
      activity) could not be detected in the soil crust, which is the biologically most
      important layer in desert soils. All pmoA sequences belonged to yet uncultured
      strains. Transcript analysis showed dominance of sequences clustering within the
      JR3, formerly identified in Californian grassland soils. Our results show that
      although active methanotrophs are prevalent in arid soils they seem to be absent
      or inactive in hyperarid and disturbed arid soils. Furthermore, we postulate that
      methanotrophs of the yet uncultured JR3 cluster are the dominant atmospheric
      methane oxidizers in this ecosystem.

PMID- 19601958
TI  - Towards the human intestinal microbiota phylogenetic core.
AB  - The paradox of a host specificity of the human faecal microbiota otherwise
      acknowledged as characterized by global functionalities conserved between humans
      led us to explore the existence of a phylogenetic core. We investigated the
      presence of a set of bacterial molecular species that would be altogether
      dominant and prevalent within the faecal microbiota of healthy humans. A total of
      10 456 non-chimeric bacterial 16S rRNA sequences were obtained after cloning of
      PCR-amplified rDNA from 17 human faecal DNA samples. Using alignment or
      tetranucleotide frequency-based methods, 3180 operational taxonomic units (OTUs)
      were detected. The 16S rRNA sequences mainly belonged to the phyla Firmicutes
      (79.4%), Bacteroidetes (16.9%), Actinobacteria (2.5%), Proteobacteria (1%) and
      Verrumicrobia (0.1%). Interestingly, while most of OTUs appeared individual
      specific, 2.1% were present in more than 50% of the samples and accounted for
      35.8% of the total sequences. These 66 dominant and prevalent OTUs included
      members of the genera Faecalibacterium, Ruminococcus, Eubacterium, Dorea,
      Bacteroides, Alistipes and Bifidobacterium. Furthermore, 24 OTUs had cultured
      type strains representatives which should be subjected to genome sequence with a
      high degree of priority. Strikingly, 52 of these 66 OTUs were detected in at
      least three out of four recently published human faecal microbiota data sets,
      obtained with very different experimental procedures. A statistical model
      confirmed these OTUs prevalence. Despite the species richness and a high
      individual specificity, a limited number of OTUs is shared among individuals and
      might represent the phylogenetic core of the human intestinal microbiota. Its
      role in human health deserves further study.

PMID- 19601960
TI  - The role of antibiotics and antibiotic resistance in nature.
AB  - Investigations of antibiotic resistance from an environmental prospective shed
      new light on a problem that was traditionally confined to a subset of clinically
      relevant antibiotic-resistant bacterial pathogens. It is clear that the
      environmental microbiota, even in apparently antibiotic-free environments,
      possess an enormous number and diversity of antibiotic resistance genes, some of
      which are very similar to the genes circulating in pathogenic microbiota. It is
      difficult to explain the role of antibiotics and antibiotic resistance in natural
      environments from an anthropocentric point of view, which is focused on clinical
      aspects such as the efficiency of antibiotics in clearing infections and
      pathogens that are resistant to antibiotic treatment. A broader overview of the
      role of antibiotics and antibiotic resistance in nature from the evolutionary and
      ecological prospective suggests that antibiotics have evolved as another way of
      intra- and inter-domain communication in various ecosystems. This signalling by
      non-clinical concentrations of antibiotics in the environment results in adaptive
      phenotypic and genotypic responses of microbiota and other members of the
      community. Understanding the complex picture of evolution and ecology of
      antibiotics and antibiotic resistance may help to understand the processes
      leading to the emergence and dissemination of antibiotic resistance and also help
      to control it, at least in relation to the newer antibiotics now entering
      clinical practice.

PMID- 19601961
TI  - Metal reduction by spores of Desulfotomaculum reducens.
AB  - The bioremediation of uranium-contaminated sites is designed to stimulate the
      activity of microorganisms able to catalyze the reduction of soluble U(VI) to the
      less soluble mineral UO(2). U(VI) reduction does not necessarily support growth
      in previously studied bacteria, but it typically involves viable vegetative cells
      and the presence of an appropriate electron donor. We characterized U(VI)
      reduction by the sulfate-reducing bacterium Desulfotomaculum reducens strain MI-1
      grown fermentatively on pyruvate and observed that spores were capable of U(VI)
      reduction. Hydrogen gas - a product of pyruvate fermentation - rather than
      pyruvate, served as the electron donor. The presence of spent growth medium was
      required for the process, suggesting that an unknown factor produced by the cells
      was necessary for reduction. Ultrafiltration of the spent medium followed by
      U(VI) reduction assays revealed that the factor's molecular size was below 3 kDa.
      Pre-reduced spent medium displayed short-term U(VI) reduction activity,
      suggesting that the missing factor may be an electron shuttle, but neither
      anthraquinone-2,6-disulfonic acid nor riboflavin rescued spore activity in fresh
      medium. Spores of D. reducens also reduced Fe(III)-citrate under experimental
      conditions similar to those for U(VI) reduction. This is the first report of a
      bacterium able to reduce metals while in a sporulated state and underscores the
      novel nature of the mechanism of metal reduction by strain MI-1.

PMID- 19601962
TI  - A small population of planktonic Flavobacteria with disproportionally high growth
      during the spring phytoplankton bloom in a prealpine lake.
AB  - Bacterioplankton growth in temperate Lake Zurich (Switzerland) was studied during
      the spring phytoplankton bloom by in situ techniques and short-term dilution
      bioassays. A peak of chlorophyll a (Chl a) concentrations was followed by a rise
      of bacterial cell numbers and leucine assimilation rates, of the proportions of
      cells incorporating 5-bromo-2-deoxyuridine (BrdU), and of community net growth
      rates in dilution cultures. Incorporation of BrdU was low in Betaproteobacteria
      (2 +/- 1%), indicating that these bacteria did not incorporate the tracer.
      Pronounced growth of Betaproteobacteria in the enrichments was only observed
      after the decline of the phytoplankton bloom. An initial peak in the proportions
      of BrdU-positive Actinobacteria (30%) preceded a distinct rise of their cell
      numbers during the period of the Chl a maximum. Cytophaga-Flavobacteria (CF)
      changed little in numbers, but featured high proportions of BrdU-positive cells
      (28 +/- 12%). Moreover, CF represented > 90% of all newly formed cells in
      dilution cultures before and during the phytoplankton bloom. One phylogenetic
      lineage of cultivable Flavobacteria (FLAV2) represented a small (0.5-1%) but
      highly active population in lake plankton. The growth rates of FLAV2 in dilution
      cultures doubled during the period of the Chl a maximum, indicating stimulation
      by phytoplankton exudates. Thus, CF, and specifically Flavobacteria, appeared to
      be substantially more important for carbon transfer in Lake Zurich spring
      bacterioplankton than was suggested by their standing stocks. The high in situ
      growth potential of these bacteria might have been counterbalanced by top-down
      control.

PMID- 19601956
TI  - Microbial diversity in modern marine stromatolites, Highborne Cay, Bahamas.
AB  - Living marine stromatolites at Highborne Cay, Bahamas, are formed by microbial
      mat communities that facilitate precipitation of calcium carbonate and bind and
      trap small carbonate sand grains. This process results in a laminated structure
      similar to the layering observed in ancient stromatolites. In the modern marine
      system at Highborne Cay, lamination, lithification and stromatolite formation are
      associated with cycling between three types of microbial communities at the
      stromatolite surface (Types 1, 2 and 3, which range from a leathery microbial mat
      to microbially fused sediment). Examination of 923 universal small-subunit rRNA
      gene sequences from these communities reveals that taxonomic richness increases
      during transition from Type 1 to Type 3 communities, supporting a previous model
      that proposed that the three communities represent different stages of mat
      development. The phylogenetic composition also changes significantly between
      these community types and these community changes occur in concert with variation
      in biogeochemical rates. The dominant bacterial groups detected in the
      stromatolites include Alphaproteobacteria, Planctomycetes, Cyanobacteria and
      Bacteroidetes. In addition, the stromatolite communities were found to contain
      novel cyanobacteria that may be uniquely associated with modern marine
      stromatolites. The implications of these findings are discussed in the context of
      current models for stromatolite formation.

PMID- 19601959
TI  - Ammonia-oxidizing Archaea in the Arctic Ocean and Antarctic coastal waters.
AB  - We compared abundance, distributions and phylogenetic composition of
      Crenarchaeota and ammonia-oxidizing Archaea (AOA) in samples collected from
      coastal waters west of the Antarctic Peninsula during the summers of 2005 and
      2006, with samples from the central Arctic Ocean collected during the summer of
      1997. Ammonia-oxidizing Archaea and Crenarchaeota abundances were estimated from
      quantitative PCR measurements of amoA and 16S rRNA gene abundances. Crenarchaeota
      and AOA were approximately fivefold more abundant at comparable depths in the
      Antarctic versus the Arctic Ocean. Crenarchaeota and AOA were essentially absent
      from the Antarctic Summer Surface Water (SSW) water mass (0-45 m depth). The
      ratio of Crenarchaeota 16S rRNA to archaeal amoA gene abundance in the Winter
      Water (WW) water mass (45-105 m depth) of the Southern Ocean was much lower
      (0.15) than expected and in sharp contrast to the ratio (2.0) in the Circumpolar
      Deep Water (CDW) water mass (105-3500 m depth) immediately below it. We did not
      observe comparable segregation of this ratio by depth or water mass in Arctic
      Ocean samples. A ubiquitous, abundant and polar-specific crenarchaeote was the
      dominant ribotype in the WW and important in the upper halocline of the Arctic
      Ocean. Our data suggest that this organism does not contain an ammonia
      monooxygenase gene. In contrast to other studies where Crenarchaeota populations
      apparently lacking amoA genes are found in bathypelagic waters, this organism
      appears to dominate in well-defined, ammonium-rich, near-surface water masses in
      polar oceans.

PMID- 19601963
TI  - The response of the marine bacterium Sphingopyxis alaskensis to solar radiation
      assessed by quantitative proteomics.
AB  - The adaptive response of the marine bacterium Sphingopyxis alaskensis RB2256 to
      solar radiation (both visible and ultraviolet) was assessed by a quantitative
      proteomic approach using iTRAQ (isobaric tags for relative and absolute
      quantification). Both growth phase (mid-log and stationary phase) and duration
      (80 min or 8 h) of different light treatments (combinations of visible light, UV
      A and UV-B) were assessed relative to cultures maintained in the dark. Rates of
      total protein synthesis and viability were also assessed. Integrating knowledge
      from the physiological experiments with quantitative proteomics of the 12
      conditions tested provided unique insight into the adaptation biology of UV and
      visible light responses of S. alaskensis. High confidence identifications were
      obtained for 811 proteins (27% of the genome), 119 of which displayed significant
      quantitative differences. Mid-log-phase cultures produced twice as many proteomic
      changes as stationary-phase cultures, while extending the duration of irradiation
      exposure of stationary-phase cultures did not increase the total number of
      quantitative changes. Proteins with significant quantitative differences were
      identified that were characteristic of growth phase and light treatment, and
      cellular processes, pathways and interaction networks were determined. Key
      factors of the solar radiation adaptive response included DNA-binding proteins
      implicated in reducing DNA damage, detoxification of toxic compounds such as
      glyoxal and reactive oxygen species, iron sequestration to minimize oxidative
      stress, chaperones to control protein re/folding, alterations to nitrogen
      metabolism, and specific changes to transcriptional and translational processes.

PMID- 19601964
TI  - Diversity and evolution of repABC type plasmids in Rhodobacterales.
AB  - The repABC operon is the prevalent replication unit of alphaproteobacterial
      plasmids. Their semi-autonomy is ensured by the essential replicase gene repC as
      well as the repAB partitioning cassette. While conserved repAB modules are
      widespread among bacterial plasmids and homologues are even responsible for
      chromosome partitioning, repC genes are exclusively present in
      Alphaproteobacteria. RepABC operons contain two strong incompatibility regions,
      namely a small regulative antisense RNA gene (inc alpha) and a palindromic
      centromere region (inc beta), which were previously used to classify these
      replicons. The present survey pursued a complementary strategy essentially
      following the rationale that all plasmids identified from a single bacterium are
      per se compatible. We established a novel classification scheme for plasmids
      based on comprehensive phylogenetic analyses of repC, repA and repB genes. Our
      case study is focused on the Roseobacter clade (Rhodobacterales), one of the most
      successful lineages of the marine bacterioplankton. Its global significance was
      shown in several studies and the interest in these organisms is reflected by more
      than 40 upcoming genome projects. Based on phylogenetic RepC analyses we
      identified nine compatibility groups that are expected to stably coexist within
      the same cell. This prediction is supported by RepA and RepB phylogenies,
      moreover independent evidence is delivered by the group specificity of highly
      conserved palindromes (inc beta).

PMID- 19601965
TI  - Very high prevalence of thyroid nodules detected by high frequency (13 MHz)
      ultrasound examination.
AB  - BACKGROUND: The prevalence of thyroid nodules in a healthy population is high: in
      the German Papillon study, nationwide ultrasound screening of more than 90 000
      people using 7.5 MHz scanners revealed the presence of thyroid nodules in 33% of
      the normal population. A study employing more sensitive 13 MHz scanners has not
      been conducted so far. MATERIALS AND METHODS: Six hundred and thirty-five
      consecutive patients (33% female, 67% male, mean 56.7 years) presenting for a
      preventive health check up underwent ultrasound screening of the thyroid gland
      (Siemens Acuson Antares, 13 MHz-linear scanner, B-mode and Power mode) and
      measurement of the basal TSH (thyroid stimulating hormone) value. Size and degree
      of vascularization of the thyroid gland and of nodules were determined and
      analysed retrospectively. RESULTS: In 432 of 635 patients, thyroid nodules could
      be detected with an increasing incidence with age, in 338 without goiter. Mean
      thyroid size was 12.3 mL for women and 20.5 mL for men correlating strongly with
      body weight. Fifty-three percentage of the nodules were smaller than 5 mm.
      Incidence of thyroid dysfunction was only 4%. No cancerous lesions could be
      found. CONCLUSIONS: Using the 13 MHz technology, we found a substantially higher
      prevalence of thyroid nodules (68%) than the Papillon study (33%). Even if our
      population is older than in Papillon, the difference remains in comparable age
      groups. This is due to the higher sensitivity of 13 MHz scanning. Our study
      underlines the clinical significance of iodine deficiency and should renew the
      discussion on routine iodine supplementation.

PMID- 19601968
TI  - Patterns and consequences of vertebrate Emx gene duplications.
AB  - We have cloned and analyzed two Emx genes from the lamprey Petromyzon marinus and
      our findings provide insight into the patterns and developmental consequences of
      gene duplications during early vertebrate evolution. The Emx gene family presents
      an excellent case for addressing these issues as gnathostome vertebrates possess
      two or three Emx paralogs that are highly pleiotropic, functioning in or being
      expressed during the development of several vertebrate synapomorphies. Lampreys
      are the most primitive extant vertebrates and characterization of their
      development and genomic organization is critical for understanding vertebrate
      origins. We identified two Emx genes from P. marinus and analyzed their phylogeny
      and their embryological expression relative to other chordate Emx genes. Our
      phylogenetic analysis shows that the two lamprey Emx genes group independently
      from the gnathostome Emx1, Emx2, and Emx3 paralogy groups. Our expression
      analysis shows that the two lamprey Emx genes are expressed in distinct spatial
      and temporal patterns that together broadly encompass the combined sites of
      expression of all gnathostome Emx genes. Our data support a model wherein large
      scale regulatory evolution of a single Emx gene occurred after the
      protochordate/vertebrate divergence, but before the vertebrate radiation. Both
      the lamprey and gnathostome lineages then underwent independent gene duplications
      followed by extensive paralog subfunctionalization. Emx subfunctionalization in
      the telencephalon is remarkably convergent and refines our understanding of
      lamprey forebrain patterning. We also identify lamprey-specific sites of
      expression that indicate either neofunctionalization in lampreys or sites
      specific nonfunctionalization of all gnathostome Emx genes. Overall, we see only
      very limited correlation between Emx gene duplications and the acquisition of
      novel expression domains.

PMID- 19601967
TI  - A sensitized genetic background reveals evolution near the terminus of the
      Caenorhabditis germline sex determination pathway.
AB  - Caenorhabditis elegans and Caenorhabditis briggsae are both self-fertile
      hermaphroditic nematodes that evolved independently from male/female ancestors.
      In C. elegans, FEM-1, FEM-2, and FEM-3 specify male fates by promoting
      proteolysis of the male-repressing transcription factor, TRA-1. Phenotypes of tra
      1 and fem mutants are consistent with this simple linear model in the soma, but
      not in the germline. While both XX and XO tra-1(lf) mutants have functional male
      somas, they produce both sperm and oocytes. Further, all three tra-1; fem double
      mutants retain the expected male soma, but make only oocytes (the germline fem
      phenotype). Thus, a poorly characterized tra-1 activity is important for
      sustained male spermatogenesis, and the fem genes affect germline sexual fate
      independently of their role in regulating TRA-1. C. briggsae tra-1 mutants are
      phenotypically identical to their C. elegans counterparts, while the fem mutants
      differ in the germline: XX and XO C. elegans fem mutants are true females, but in
      C. briggsae they are self-fertile hermaphrodites. To further explore how C.
      briggsae hermaphrodites regulate germline sex, we analyzed Cb-tra-1/Cb-fem
      interactions. Cb-tra-1 is fully epistatic to Cb-fem-2 in the germline, unlike the
      orthologous C. elegans combination. In contrast, Cb-fem-3 shifts the Cb-tra-1(lf)
      germline phenotype to that of a nearly normal hermaphrodite in the context of a
      male somatic gonad. This suggests that Cb-fem-3 is epistatic to Cb-tra-1(lf) (as
      in C. elegans), and that the normal control of C. briggsae XX spermatogenesis
      targets Cb-tra-1-independent factors downstream of Cb-fem-3. The effect of Cb-fem
      3(lf) on Cb-tra-1(lf) is not mediated by change in the expression of Cb-fog-3, a
      likely direct germline target of Cb-tra-1. As Cb-fem-2 and Cb-fem-3 have
      identical single mutant phenotypes, Cb-tra-1 provides a sensitized background
      that reveals differences in how they promote male germline development. These
      results represent another way in which C. briggsae germline sex determination is
      incongruent with that of the outwardly similar C. elegans.

PMID- 19601969
TI  - Developmental expression of apterous/Lhx2/9 in the sepiolid squid Euprymna
      scolopes supports an ancestral role in neural development.
AB  - The transcription factors Apterous/Lhx2/9 play many pivotal roles in the
      development of protostomes and deuterostomes, most notably limb patterning, eye
      morphogenesis, and brain development. Full-length apterous/lhx2/9 homologs have
      been isolated from several invertebrate species, but hitherto not from a
      lophotrochozoan. Here, we report the isolation, characterization, and spatio
      temporal expression of apterous in the sepiolid squid Euprymna scolopes. The
      isolated composite cDNA encodes a hypothetical protein of 448 amino acid residues
      with a typical LIM-homeodomain (LIM-HD) structure and the greatest overall
      sequence similarity to vertebrate Lhx2/9 proteins. The Euprymna scolopes apterous
      (Es-ap) expression patterns provided no indication of a role in the early
      dorso/ventral patterning or growth of the arm crown that showed expression only
      in two ventral cords running in parallel inside the arms and tentacles and at the
      base of the suckers, a region rich in nerve endings and chemosensory neurons. The
      Es-ap hybridization signal was also conspicuous in the eyes, olfactory organs,
      optic lobes, and in several lobes of the supraesophageal mass, among these the
      olfactory and vertical lobes, and paravertical bodies. The observed expression
      patterns suggest gene involvement in eye morphogenesis and neural wiring of
      sensory structures, including those for olfaction and vision.

PMID- 19601970
TI  - Characterization of the tammar wallaby (Macropus eugenii) whey acidic protein
      gene: new insights into the function of the protein.
AB  - Whey acidic protein (WAP) belongs to a family of four disulfide core (4-DSC)
      proteins rich in cysteine residues and is the principal whey protein found in
      milk of a number of mammalian species. Eutherian WAPs have two 4-DSC domains,
      whereas marsupial WAPs are characterized by the presence of an additional domain
      at the amino terminus. Structural and expression differences between marsupial
      and eutherian WAPs have presented challenges to identifying physiological
      functions of the WAP protein. We have characterized the genomic structure of
      tammar WAP (tWAP) gene, identified its chromosomal localization and investigated
      the potential function of tWAP. We have demonstrated that tWAP and domain III
      (DIII) of the protein alone stimulate proliferation of a mouse mammary epithelial
      cell line (HC11) and primary cultures of tammar mammary epithelial cells (Wall
      MEC), whereas deletion of DIII from tWAP abolishes this proliferative effect.
      However, tWAP does not induce proliferation of human embryonic kidney (HEK293)
      cells. DNA synthesis and expression of cyclin D1 and cyclin-dependent kinase-4
      genes were significantly up-regulated when Wall-MEC and HC11 cells were grown in
      the presence of either tWAP or DIII. These data suggest that DIII is the
      functional domain of the tWAP protein and that evolutionary pressure has led to
      the loss of this domain in eutherians, most likely as a consequence of adopting a
      reproductive strategy that relies on greater investment in development of the
      newborn during pregnancy.

PMID- 19601971
TI  - Bindin from a sea star.
AB  - The genetic basis for the evolution of development includes genes that encode
      proteins expressed on the surfaces of sperm and eggs. Previous studies of the
      sperm acrosomal protein bindin have helped to characterize the adaptive evolution
      of gamete compatibility and speciation in sea urchins. The absence of evidence
      for bindin expression in taxa other than the Echinoidea has limited such studies
      to sea urchins, and led to the suggestion that bindin might be a sea urchin
      specific molecule. Here we characterize the gene that encodes bindin in a
      broadcast-spawning asterinid sea star (Patiria miniata). We describe the sequence
      and domain structure of a full-length bindin cDNA and its single intron. In
      comparison with sea urchins, P. miniata bindin is larger but the two molecules
      share several general features of their domain structure and some sequence
      features of two domains. Our results extend the known evolutionary history of
      bindin from the Mesozoic (among the crown group sea urchins) into the early
      Paleozoic (and the common ancestor of eleutherozoans), and present new
      opportunities for understanding the role of bindin molecular evolution in sexual
      selection, life history evolution, and speciation among sea stars.

PMID- 19601973
TI  - Postembryonic development of the posterior lateral line in the zebrafish.
AB  - The posterior lateral line (PLL) of zebrafish comprises seven to eight sense
      organs at the end of embryogenesis, arranged in a single antero-posterior line
      that extends along the horizontal myoseptum from the ear to the tip of the tail.
      At the end of larval life, four antero-posterior lines extend on the trunk and
      tail, comprising together around 60 sense organs. The embryonic pattern is
      largely conserved among teleosts, although adult patterns are very diverse. Here
      we describe the transition from embryonic to juvenile pattern in the zebrafish,
      to provide a framework for understanding how the diversity of adult patterns
      comes about. We show that the four lines that extend over the adult body
      originate from latent precursors laid down by migrating primordia that arise
      during embryogenesis. We conclude that, in zebrafish, the entire development of
      the PLL system up to adulthood can be traced back to events that took place
      during the first 2 days of life. We also show that the transition from embryonic
      to adult pattern involves few distinct operations, suggesting that the diversity
      of patterns among adult teleosts may be due to differential control of these few
      operations acting upon common embryonic precursors.

PMID- 19601972
TI  - A phylogenetic approach to gene expression data: evidence for the evolutionary
      origin of mammalian leukocyte phenotypes.
AB  - The evolution of multicellular organisms involved the evolution of specialized
      cell types performing distinct functions; and specialized cell types presumably
      arose from more generalized ancestral cell types as a result of mutational event,
      such as gene duplication and changes in gene expression. We used characters based
      on gene expression data to reconstruct evolutionary relationships among 11 types
      of lymphocytes by the maximum parsimony method. The resulting phylogenetic tree
      showed expected patterns including separation of the lymphoid and myeloid
      lineages; clustering together of granulocyte types; and pairing of phenotypically
      similar cell types such as T-helper cells type 1 and T-helper cells type 2 (Th1
      and Th2). We used phylogenetic analyses of sequence data to determine the time of
      origin of genes showing significant expression difference between Th1 and Th2
      cells. Many such genes, particularly those involved in the regulation of gene
      expression or activation of proteins, were of ancient origin, having arisen by
      gene duplication before the most recent common ancestor (MRCA) of tetrapods and
      teleosts. However, certain other genes with significant expression difference
      between Th1 and Th2 arose after the tetrapod-teleost MRCA, and some of the latter
      were specific to eutherian (placental) mammals. This evolutionary pattern is
      consistent with previous evidence that, while bony fishes possess Th1 and Th2
      cells, the latter differ phenotypically in important respects from the
      corresponding cells of mammals. Our results support a gradualistic model of the
      evolution of distinctive cellular phenotypes whereby the unique characteristics
      of a given cell type arise as a result of numerous independent mutational changes
      over hundreds of millions of years.

PMID- 19601974
TI  - Morphometric integration and modularity in configurations of landmarks: tools for
      evaluating a priori hypotheses.
AB  - Identifying the modular components of a configuration of landmarks is an
      important task of morphometric analyses in evolutionary developmental biology.
      Modules are integrated internally by many interactions among their component
      parts, but are linked to one another only by few or weak interactions.
      Accordingly, traits within modules are tightly correlated with each other, but
      relatively independent of traits in other modules. Hypotheses concerning the
      boundaries of modules in a landmark configuration can therefore be tested by
      comparing the strength of covariation among alternative partitions of the
      configuration into subsets of landmarks. If a subdivision coincides with the true
      boundaries between modules, the correlations among subsets should be minimal.
      This article introduces Escoufier's RV coefficient and the multi-set RV
      coefficient as measures of the correlation between two or more subsets of
      landmarks. These measures can be compared between alternative partitions of the
      configuration into subsets. Because developmental interactions are tissue bound,
      it is sensible to require that modules should be spatially contiguous. I propose
      a criterion for spatial contiguity for sets of landmarks using an adjacency
      graph. The new methods are demonstrated with data on shape of the wing in
      Drosophila melanogaster and the mandible of the house mouse.

PMID- 19601976
TI  - Demonstration of a heritable component of the variation in segment number in the
      centipede Strigamia maritima.
AB  - Here we address the question of how arthropod segment number may evolve by
      reporting the results of further work on the model system Strigamia maritima.
      Recently, we showed that there was a plastic component of the variation in
      segment number within this species; now we demonstrate that there is also a
      heritable component. This is important because it enables a connection to be made
      between the known latitudinal trend among species of geophilomorph centipedes
      (more segments at lower latitudes) and the parallel trend within them. This
      latter trend is best documented in S. maritima but is also known in several other
      species. However, while a general connection between the inter- and intraspecific
      trends can now be made, deciding upon a specific hypothesis of the nature of the
      selection involved is still problematic. We provide two alternative hypotheses,
      one based on the temperature-related plasticity in segment number being adaptive,
      the other based on it being nonadaptive.

PMID- 19601975
TI  - Heterochronic shifts explain variations in a sequentially developing repeated
      pattern: palatal ridges of muroid rodents.
AB  - Metazoans are largely made of repeated parts, and metazoan evolution is marked by
      changes in the number of these parts, called meristic evolution. Understanding
      the mechanisms associated with meristic changes is thus a critical issue to
      evolutionary developmental biology. Palatal rugae are sensory ridges regularly
      arranged on the hard palate of mammals. They develop sequentially following mesio
      distal growth of the palate, and activation-inhibition mechanisms very likely
      control spacing and timing of this sequential addition. In this study, we
      characterized trends in rugae number evolution among muroid rodents, showing that
      most species display 8+/-1 rugae, changes by one being very frequent in the
      phylogeny. We then compared development of three muroid species: mouse (nine
      rugae), rat (eight), and golden hamster (seven). We showed that palatal growth
      rate, spacing, and addition rate in mouse/rat were remarkably similar (with
      respect to the embryo size difference), and that increase to nine rugae in mouse
      is achieved by postponing the end of the addition process (hypermorphosis). Such
      a heterochronic shift may be typical of +/-1 variations observed among muroid
      rodents. In contrast, decrease to seven rugae in golden hamster is attributed to
      early growth termination (progenesis) of the palate, which correlates with the
      severe shortening of gestation in this species. Our results provide an
      experimental support to the intuitive view that heterochronies are especially
      relevant to meristic evolution of traits that rely on a sequential addition
      process. We also interpret our results in the light of developmental constraints
      specifically linked to this kind of process.

PMID- 19601977
TI  - Post-embryonic development of the Furongian (late Cambrian) trilobite Tsinania
      canens: implications for life mode and phylogeny.
AB  - The current concept of the order Asaphida was proposed to accommodate some
      Cambrian and Ordovician trilobite clades that are characterized by the possession
      of a ventral median suture. The family Tsinaniidae was recently suggested to be a
      member of the order Asaphida on the basis of its close morphological similarity
      to Asaphidae. Postembryonic development of the tsinaniid trilobite, Tsinania
      canens, from the Furongian (late Cambrian) Hwajeol Formation of Korea, reveals
      that this trilobite had an adult-like protaspis. Notable morphological changes
      with growth comprise the effacement of dorsal furrows, sudden degeneration of
      pygidial spines, regression of genal spines, and loss of a triangular rostral
      plate to form a ventral median suture. Programmed cell death may be responsible
      for degenerating the pygidial and genal spines during ontogeny. Morphological
      changes with growth, such as the loss of pygidial spines, modification of pleural
      tips, and effacement of dorsal furrows, suggest that T. canens changed its life
      mode during ontogeny from benthic crawling to infaunal. The protaspid morphology
      and the immature morphology of T. canens retaining genal and pygidial spines
      suggest that tsinaniids bear a close affinity to leiostegioids of the order
      Corynexochida. Accordingly, development of a ventral median suture in T. canens
      demonstrates that the ventral median suture could have evolved polyphyletically,
      and thus the current concept of the order Asaphida needs to be revised.

PMID- 19601979
TI  - Effector pathways during eczematous dermatitis: where inflammation meets cell
      death.
AB  - During eczematous skin inflammation, the main constituents of the skin,
      keratinocytes (KC), play an important role in inducing and shaping the
      immunological response to environmental stimuli. This review focuses on the
      epidermal inflammation caused by keratinocyte-T cell interactions arising from a
      disturbed barrier function of the skin. In eczematous dermatitis, activated
      dermis- and epidermis-infiltrating T cells target KC for apoptosis. In turn,
      damaged KC respond by secreting inflammatory mediators, thus effecting further
      recruitment of immunocytes to inflamed skin. Further advances will come from
      identification of the immunoregulatory mechanisms involved in the pathogenesis of
      eczematous dermatitis. Potential therapeutic interventions are discussed.

PMID- 19601981
TI  - Leptin and the skin: a new frontier.
AB  - Here, we examine the currently available information which supports that the
      adipokine, leptin, is a major player in the biology and pathology of mammalian
      skin and its appendages. Specifically, the potent metabolic effects of leptin and
      its mimetics may be utilized to improve, preserve and restore skin regeneration
      and hair cycle progression, and may halt or even partially reverse some aspects
      of skin ageing. Since leptin can enhance mitochondrial activity and biogenesis,
      this may contribute to the wound healing-promoting and hair growth-modulatory
      effects of leptin. Leptin dependent intracellular signalling by the Janus kinase
      2 dependent signal transducer and activator of transcription 3, adenosine
      monophosphate kinase, and peroxisome proliferator-activated receptor (PPAR) gamma
      coactivator/PPAR converges to mediate mitochondrial metabolic activation and
      enhanced cell proliferation which may orchestrate the potent developmental,
      trophic and protective effects of leptin. Since leptin and leptin mimetics have
      already been clinically tested, investigative dermatology is well-advised to
      place greater emphasis on the systematic exploration of the cutaneous dimensions
      and dermatological potential of this pleiotropic hormone.

PMID- 19601980
TI  - Keratinocytes efficiently process endogenous antigens for cytotoxic T-cell
      mediated lysis.
AB  - The generation of a robust CD8(+) cytotoxic T lymphocyte (CTL) response is a key
      feature of many immunotherapeutic strategies against epithelial tumors and
      virally infected epithelial tissue. However, surprisingly few studies have
      addressed whether primary epithelial cells, expressing defined endogenous
      antigens, are good targets for CTL-mediated lysis. Here, we show that primary
      keratinocytes (KCs), expressing endogenous ovalbumin (OVA) as a transgene,
      present measurable H-2K(b)/SIINFEKL complexes at the cell surface and are killed
      by OVA-specific CTL. Target cell lysis was comparable with a more traditional CTL
      target cell, EL4, and was enhanced by KC pretreatment with interferon-gamma.
      These results suggest that primary KCs will be susceptible to CTL-mediated
      apoptosis when endogenous KC antigens are targeted during immunotherapy.

PMID- 19601982
TI  - MAP17 is associated with the T-helper cell cytokine-induced down-regulation of
      filaggrin transcription in human keratinocytes.
AB  - In the meta-analysis of public microarray databases for different skin diseases,
      we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2,
      SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may
      be potentially associated with the abnormal keratinocyte differentiation. To
      demonstrate this postulation, we alternatively evaluated whether the genes of
      interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in
      normal human epidermal keratinocytes (NHEK). We found that MAP17 was
      significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4),
      IL-6, IL-17A or IL-22 in NHEK. Interestingly, MAP17 was originally reported to
      interact with PDZK1; in turn, the PDZK1 gene is localized within the atopic
      dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate
      whether MAP17 regulates the expression of cornified envelope-associated genes at
      the 1q21 locus, such as filaggrin, loricrin and involucrin, we found that the
      over-expression of MAP17 in HaCaT keratinocytes significantly decreased the
      expression of filaggrin. Taken together, the Th cell cytokine-induced up
      regulation of MAP17 expression may be linked to the down-regulation of filaggrin
      in NHEK, which may be associated with the abnormal epidermal differentiation
      observed in the dermatological diseases.

PMID- 19601984
TI  - Extrinsic ageing in the human skin is associated with alterations in the
      expression of hyaluronic acid and its metabolizing enzymes.
AB  - Extrinsic skin ageing or 'photoageing', as opposed to intrinsic skin ageing, is
      the result of exposure to external factors, mainly ultraviolet irradiation.
      Glycosaminoglycans (GAG) and particularly hyaluronic acid (HA) are major
      components of the cutaneous extracellular matrix involved in tissue repair.
      However, their involvement in extrinsic skin ageing remains elusive. In this
      study, we investigated the expression of HA and its metabolizing enzymes in
      photoexposed and photoprotected human skin tissue specimens, obtained from the
      same patient. Total GAG were isolated, characterized using specific GAG-degrading
      enzymes and separated by electrophoresis on cellulose acetate membranes and
      polyacrylamide gels. Quantitation of HA in total GAG was performed using ELISA.
      Gene expression of hyaluronan synthases (HAS), hyaluronidases (HYAL) and HA
      receptors CD44 and receptor for HA-mediated motility (RHAMM) was assessed by RT
      PCR. We detected a significant increase in the expression of HA, of lower
      molecular mass, in photoexposed skin as compared with photoprotected skin. This
      increase was associated with a significant decrease in the expression of HAS1 and
      an increase in the expression of HYAL1-3. Furthermore, the expression of HA
      receptors CD44 and RHAMM was significantly downregulated in photoexposed as
      compared with photoprotected skin. These findings indicate that extrinsic skin
      ageing is characterized by distinct homoeostasis of HA. The elucidation of the
      role of HA homoeostasis in extrinsic skin ageing may offer an additional approach
      in handling cutaneous ageing.

PMID- 19601985
TI  - Misleading one-stage coagulation factor assay during rFVIIa treatment in lupus
      patient.

PMID- 19601983
TI  - MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer.
AB  - The squamous cell cancers (SCC) of renal transplant recipients are more
      aggressive and metastasize earlier than those of the non-immunocompromised
      population. Matrix metalloproteinases (MMPs) have a central role in tumor
      initiation, invasion and metastasis. Our aim was to compare the expression of
      MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and
      the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5
      Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs,
      nine of Bowen's disease and timed back skin biopsies of mice with selective
      inhibition of Rel/NF-kappaB signalling were performed. Semiquantitatively
      assessed stromal MMP-10 expression was higher (P = 0.009) in the control group
      when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression
      did not differ between the groups but stromal fibroblasts of the control SCCs
      tended to express MMP-21 more abundantly. MMP-10 expression was observed already
      in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in
      inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and
      invasive cancer were negative. Our results suggest that MMP-10 may be important
      in the initial stages of SCC progression and induced in the stroma relating to
      the general host-response reaction to skin cancer. MMP-21 does not associate with
      invasion of SCC but may be involved in keratinocyte differentiation.

PMID- 19601986
TI  - Clinical variability of haemophilia A and B in Mexican families by factor V
      Leiden G1691A, prothrombin G20210A and MTHFR C677T/A1298C.

PMID- 19601987
TI  - Using a minigene approach to characterize a novel splice site mutation in human
      F7 gene causing inherited factor VII deficiency in a Chinese pedigree.
AB  - Factor VII deficiency which transmitted as an autosomal recessive disorder is a
      rare haemorrhagic condition. The aim of this study was to identify the molecular
      genetic defect and determine its functional consequences in a Chinese pedigree
      with FVII deficiency. The proband was diagnosed as inherited coagulation FVII
      deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%).
      All nine exons and their flanking sequence of F7 gene were amplified by
      polymerase chain reaction (PCR) for the proband and the PCR products were
      directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572
      1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's
      F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A,
      ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes,
      spanning from intron 4 to intron 7 and carrying either an A or a G at position -1
      of intron 5, were constructed and transiently transfected into human embryonic
      kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts
      from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription
      study. Sequencing of the RT-PCR products from the mutant transfectant
      demonstrated the production of an erroneously spliced mRNA with exon 6 skipping,
      whereas a normal splicing occurred in the wide type transfectant. The aberrant
      mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor
      VII deficiency in this pedigree.

PMID- 19601988
TI  - Haemophilia gene therapy: the patients' perspective.

PMID- 19601989
TI  - Monthly recombinant tissue plasminogen activator administration to implantable
      central venous access devices decreases infections in children with haemophilia.
AB  - Central venous access devices (CVAD) have been effectively used in the care of
      haemophilia patients. This is particularly true in children, who often have
      difficult venous access. CVAD complications (infection and thrombosis), risk
      factors, and complication rates, have been well-documented. However, effective
      interventions which decrease complication rates have not been identified. In this
      study, we review our experience with the use of monthly recombinant tissue
      plasminogen activator (rtPA) administration in haemophilia patients with fully
      implanted CVADs. Data on 19 haemophilia patients with 24 CVADs were available for
      analysis, with a total of 24 520 CVAD days. An infection rate of 0.04 infections
      per 1000 CVAD days and a thrombosis rate of 0.04 thrombi per 1000 CVAD days was
      observed. The observed infectious complication rate is at least one logarithm
      lower than many published CVAD infection rates in haemophilia patients who have
      not received rtPA administration. No bleeding complications were noted. Monthly
      rtPA is safe and appears to be effective in decreasing CVAD infection rates.
      Larger, randomized controlled studies are indicated to validate this finding.

PMID- 19601990
TI  - The mutation spectrum associated with type 3 von Willebrand disease in a cohort
      of patients from the north west of England.
AB  - Type 3 von Willebrand disease (VWD) is a severe autosomal recessive inherited
      bleeding disorder. In affected individuals the underlying von Willebrand factor
      gene (VWF) mutations frequently remain uncharacterized. The aim of this study was
      to investigate the molecular basis of type 3 VWD in patients (11 Caucasians and 9
      of Asian origin) attending the haemophilia centres at Central Manchester NHS
      Trust. A combination of DNA sequencing of VWF genomic and complementary DNA was
      performed to identify mutations in the patient cohort. Fifteen different VWF
      mutations were identified at the genomic DNA level: two gene conversion events,
      three nonsense, three frameshift, one missense, two splice site, one insertion
      deletion and three deletion mutations. Homozygosity or compound heterozygosity
      for mutations was present in 15 of the 20 patients. In the remaining five
      individuals, heterozygosity for a single VWF mutation was identified in four
      cases and one patient had no detectable VWF mutation. Analysis of platelet
      derived VWF RNA from these five individuals revealed heterozygosity for a
      deletion of exons 4 and 5 in four cases. The remaining patient was heterozygous
      for a three base deletion which had already been identified at the DNA level.
      Overall the observed VWF genotype explained the phenotype in 18 of the 20
      patients investigated. In genetic studies in type 3 VWD, if VWF mutations are not
      detected at the DNA level, RNA analysis should be performed to search for
      intronic mutations, heterozygous deletions or aberrant splicing/post
      transcriptional events. However, this may still not explain all cases of
      previously phenotypically diagnosed type 3 VWD.

PMID- 19601991
TI  - Why are some care homes better than others? An empirical study of the factors
      associated with quality of care for older people in residential homes in Surrey,
      England.
AB  - This paper reports an empirical study that investigated associations between the
      quality of care received by older people in residential settings and features of
      the care homes in which they live. Data were gathered from the first announced
      inspection reports (2002-2003) of all 258 care homes for older people in one
      county of England (Surrey). The number of inspected standards failed in each home
      was used as the main indicator of quality of care. Independent variables (for
      each home) were: size, type, specialist registration, on-site nursing, ownership,
      year registered, location, maximum fee, vacancies, resident dependency, whether
      the home took publicly funded residents, care staff qualifications and managerial
      quality. Quality of care was modelled using a Poisson count maximum likelihood
      method based on 245 (91%) of the inspected homes for which relevant data were
      available. The results showed that quality of care (as defined by failures on
      national standards) was statistically associated with features of care homes and
      their residents. A higher probability of failing a standard was significantly
      associated with being a home that: was a for-profit small business (adjusted risk
      ratio (RR) = 1.17); was registered before 2000 (adj. RR = 1.22), accommodated
      publicly funded residents (adj. RR = 1.12); was registered to provide nursing
      care (adj. RR = 1.12). Fewer failures were associated with homes that were
      corporate for-profit (adj. RR = 0.82); held a specialist registration (adj. RR =
      0.91); charged higher maximum fees (adj. RR = 0.98 per 100 pound sterling unit).
      A secondary analysis revealed a stronger model: higher scores on managerial
      standards correlated with fewer failures on other standards (r = 0.65, P <
      0.001). The results of this study may help inform future policy. They are
      discussed in the context of alternative approaches to measuring quality of
      residential care, and in terms of their generalisability.

PMID- 19601992
TI  - A randomized double-blind pilot study of serum phosphorus normalization in
      chronic kidney disease: a new paradigm for clinical outcomes studies in
      nephrology.

PMID- 19601994
TI  - Laryngeal squamous cell carcinoma in HIV-positive patients: lack of association
      with human papillomavirus infection.
AB  - OBJECTIVES: Neoplasms associated with human papillomavirus (HPV) infection occur
      at increased frequency in patients with HIV infection/AIDS. Although laryngeal
      squamous cell carcinomas (LSCCs) in HIV-positive patients are uncommon, a higher
      incidence of this malignancy in HIV-positive patients than in the general
      population has been reported. As a proportion of LSCCs are associated with HPV in
      the general population, the clinicopathological features of a series of LSCCs
      developing in HIV-positive patients were evaluated to investigate the possible
      relationship with HPV infection, and infection with other oncogenic viruses.
      METHODS: All HIV-positive patients with LSCC diagnosed at a single institution
      from 1998 to 2007 were retrospectively evaluated. The clinicopathological
      features were analysed and tissues were tested by polymerase chain reaction
      (PCR), using the short PCR fragment 10 (SPF10) primer, a highly sensitive method
      for HPV DNA detection. Immunohistochemical studies for HIV p24, p16(INK4a) and
      p53 were performed. Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8)
      were also investigated. RESULTS: Six out of 4987 HIV-infected patients seen in
      this period in the Infectious Diseases Department developed LSCC (median age 41.5
      years; male to female ratio 1:1). All patients were heavy smokers and the tumours
      presented at an advanced clinical stage. HPV was not detected in any tumour, not
      even in two patients with coexisting HPV-associated gynaecological neoplasm.
      Staining for HIV p24 and p16(INK4a) was negative, whereas p53 was positive in
      half the cases. EBV and HHV-8 were also negative. CONCLUSION: LSCC developing in
      HIV-positive patients is an infrequent neoplasm, not usually associated with HPV
      infection. It develops in young, heavy smokers and presents at an advanced
      clinical stage.

PMID- 19601995
TI  - Identification of new genotypic cut-off levels to predict the efficacy of
      lopinavir/ritonavir and darunavir/ritonavir in the TITAN trial.
AB  - BACKGROUND: Genotypic algorithms used to predict the clinical efficacy of
      lopinavir/ritonavir (LPV/r) have included a range of mutation lists and efficacy
      endpoints. Normally, HIV clinical trials are powered to detect a difference
      between treatment arms of 10-12% for the endpoint of viral load suppression <50
      HIV-1 RNA copies/mL. The TITAN trial evaluated LPV/r vs. darunavir/ritonavir
      (DRV/r) in treatment-experienced patients with viral load >1000 copies/mL. This
      analysis aimed to re-evaluate resistance algorithms for LPV/r in the TITAN trial.
      METHODS: Baseline genotype data were classified using seven genotypic resistance
      algorithms: International AIDS Society USA (IAS-USA) LPV mutations (current cut
      off=6), Abbott 2007 mutation list (cut-off=3), ANRS mutations (cut-off=4), FDA
      mutations (cut-off=3), Stanford, REGA and IAS-USA major protease inhibitor (PI)
      mutations. Efficacy in the TITAN trial (HIV-1 RNA <50 copies/mL at week 48) was
      correlated with the number of mutations from each list, to show the 'efficacy
      advantage cut-off level': the number of mutations from each list associated with
      a difference in efficacy between treatment arms of at least 12%. RESULTS:
      Multivariate logistic regression analysis identified lower genotypic cut-off
      levels than previously reported where there was at least 12% lower efficacy for
      LPV/r vs. DRV/r. These efficacy advantage cut-off levels were: IAS-USA LPV
      mutations, cut-off=3; Abbott 2007, cut-off=2; ANRS LPV, cut-off=3; FDA LPV
      mutations, cut-off=2; major IAS-USA PI mutations, cut-off=1; Stanford algorithm,
      cut-off=low-level LPV resistance; REGA algorithm, cut-off=intermediate-level LPV
      resistance. There were linear falls in HIV-1 RNA suppression rates with rising
      mutation counts in the TITAN, French LPV ATU, BMS-045 and RESIST trials.
      CONCLUSIONS: The analysis identified more sensitive cut-off levels for LPV
      genotypic algorithms, below those currently used.

PMID- 19601996
TI  - Depression in patients with HIV is under-diagnosed: a cross-sectional study in
      Denmark.
AB  - BACKGROUND: International studies suggesting that 20-37% of HIV-positive patients
      have diagnosable depression may underestimate the prevalence of this condition.
      The aim of this study was to investigate the prevalence of depression among HIV
      positive patients in an out-patient clinic in Denmark and to detect factors of
      importance for the development of depression. METHODS: In 2005, a population of
      205 HIV-positive patients was included in a questionnaire-based study. The Beck
      Depression Inventory II (BDI-II) was used to assess the prevalence and severity
      of depressive symptoms. Patients with a BDI score of 20 or above were offered a
      clinical evaluation by a consultant psychiatrist. RESULTS: Symptoms of depression
      (BDI>14) were observed in 77 (38%) patients and symptoms of major depression
      (BDI>or=20) in 53 (26%). Eighteen patients subsequently started treatment with
      anti-depressants. In a reduced logistic regression model, self-reported stress,
      loneliness, constant thoughts about HIV and being in a difficult financial
      situation were associated with risk of depression. Patients at risk of major
      depression were nearly six times more likely to have missed at least one dose of
      highly active antiretroviral therapy (HAART) in the 4 days prior to assessment
      (odds ratio 5.7, 95% confidence interval 1.7-18.6). There was a dose-response
      trend in relation to unsafe sex (P=0.03). CONCLUSIONS: The study found that
      depression was under-diagnosed among HIV-positive patients and was associated
      with stress, loneliness, a difficult financial situation, low adherence and
      unsafe sex. Screening for depression should be conducted regularly to provide
      full evaluation and relevant psychiatric treatment. This is particularly
      important at the time of diagnosis and before initiating HAART.

PMID- 19601993
TI  - Deferred modification of antiretroviral regimen following documented treatment
      failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD).
AB  - OBJECTIVE: The aim of the study was to examine the rates and predictors of
      treatment modification following combination antiretroviral therapy (cART)
      failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational
      Database (TAHOD). METHODS: Treatment failure (immunological, virological and
      clinical) was defined by World Health Organization criteria. Countries were
      categorized as high or low income by World Bank criteria. RESULTS: Among 2446
      patients who initiated cART, 447 were documented to have developed treatment
      failure over 5697 person-years (7.8 per 100 person-years). A total of 253
      patients changed at least one drug after failure (51.6 per 100 person-years).
      There was no difference between patients from high- and low-income countries
      [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for
      Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38,
      P=0.040], a lower CD4 count (>or=51 cells/microL vs. <or=50 cells/microL;
      adjusted HR 0.61, P=0.022) and a higher HIV viral load (>or=400 HIV-1 RNA
      copies/mL vs. <400 copies/mL; adjusted HR 2.69, P<0.001) were associated with a
      higher rate of treatment modification after failure. Compared with patients from
      low-income countries, patients from high-income countries were more likely to
      change two or more drugs (67%vs. 49%; P=0.009) and to change to a protease
      inhibitor-containing regimen (48%vs. 16%; P<0.001). CONCLUSIONS: In a cohort of
      Asian patients with HIV infection, nearly half remained on the failing regimen in
      the first year following documented treatment failure. This deferred modification
      is likely to have negative implications for accumulation of drug resistance and
      response to second-line treatment. There is a need to scale up the availability
      of second-line regimens and virological monitoring in this region.

PMID- 19601998
TI  - Variation in genes of the epidermal differentiation complex in German atopic
      dermatitis patients.
AB  - The filaggrin (FLG) gene is one of the most widely replicated susceptibility
      genes for atopic dermatitis (AD) so far. Yet, FLG mutations cannot fully account
      for the original linkage peak on chromosome 1q21, a region comprising the so
      called epidermal differentiation complex (EDC). Since the EDC contains numerous
      genes relevant for epidermal differentiation, we sought to evaluate variation in
      other genes located in this region in a German AD case-control cohort. Thirty-two
      single nucleotide polymorphisms (SNPs) in 21 genes across the EDC were genotyped
      in 402 unrelated AD patients and 325 non-atopic controls by means of restriction
      enzyme digestion or TaqMan assays. Allele and genotype frequencies were tested
      for differences between patients and controls by logistic regression. Haplotype
      frequencies were evaluated using the famhap software. Except for the already
      known association with FLG, we did not identify any additional significant
      associations of EDC genes with AD. Thus, in this German cohort, there is no
      evidence that additional genes in the EDC region apart from FLG contribute
      substantially to AD pathogenesis.

PMID- 19601997
TI  - Higher risk of AIDS or death in patients with lower CD4 cell counts after virally
      suppressive HAART.
AB  - BACKGROUND: The clinical implications of a failure to achieve high CD4 cell
      counts while receiving virally suppressive highly active antiretroviral therapy
      (HAART) are uncertain. METHODS: We analysed data from HIV-infected men
      participating in the Multicenter AIDS Cohort Study (MACS) to elucidate
      associations between CD4 cell counts achieved during virally suppressive HAART
      and risks of AIDS or death. Inclusion criteria were: CD4 cell count <200
      cells/microL before HAART initiation; >or=2 viral load (VL) determinations after
      HAART initiation; and sustained viral suppression, defined as all VL <50 HIV-1
      RNA copies/mL, but allowing a single VL of 50-1000 copies/mL. RESULTS: One
      hundred and twenty-one men were included; median age was 42 years. After first VL
      <50 copies/mL, six participants had a new AIDS diagnosis and seven died. The
      median CD4 cell count change/year (cells/microL) after first VL <50 copies/mL was
      zero among patients who either developed AIDS or died vs. 39 among those who did
      not meet either endpoint (P=0.119). After controlling for time from HAART
      initiation to first VL <50 copies/mL, age at first VL <50 copies/mL, history of
      AIDS and antiretroviral therapy (ART) experience before HAART, the hazard ratio
      for AIDS or death at CD4 cell count of <or=200 vs. >350 cells/microL was 10.7
      (P=0.013), and at CD4 cell count of 201-350 vs. >350 cells/microL was 8.54
      (P=0.014). CONCLUSION: In this cohort, lower CD4 cell count at the time of viral
      suppression was associated with increased risk of AIDS or death.

PMID- 19601999
TI  - A genetic polymorphism in transforming growth factor beta receptor-2 is
      associated with serum osteopontin.
AB  - Osteopontin (OPN) is a secreted glycoprotein demonstrated to play an important
      role in inflammation. Transforming growth factor beta and a related signalling
      pathway have been implicated in control of OPN secretion. We examined the
      relationship between transforming growth factor beta receptor-1 and -2 (TGFBR1
      and 2) single nucleotide polymorphisms (SNP) and serum OPN in 296 men from the
      Health in Men Study. Serum concentrations of OPN and 58 SNPs for TGFBR1 and 2
      were assessed. One SNP in TGFBR2 was associated with serum OPN (TGFBR2
      g.20690C>T, SNP ID rs4522809, P = 0.0007) after adjusting for multiple testing.
      This study suggests that polymorphism in TGFBR2 are associated with altered
      secretion of OPN, supporting a role for transforming growth factor beta in OPN
      production.

PMID- 19602000
TI  - CTLA-4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus
      erythematosus patients.
AB  - Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing
      a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to
      be related with genetic susceptibility to various autoimmune diseases, including
      systemic lupus erythematosus (SLE). However, the effects of this polymorphism on
      clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49
      A/G polymorphisms in patients with SLE by using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and investigated the effect
      of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated
      Turkish SLE patients, all fulfilling the American College of Rheumatology
      criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype
      was a predominant genotype in the Turkish population and genotype frequencies of
      CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls
      (47%) (P = 0.015). There was a statistically significant difference in the AA
      genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P =
      0.014] distribution among patients and controls. There was also an increase in A
      allele frequency in SLE and controls, but the difference was not statistically
      significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly,
      mean age and mean age of onset disease was higher in AA homozygote SLE patients
      compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31,
      P = 0.046, respectively). There was no association between genotype and the other
      clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might
      be a risk factor for the development of SLE in Turkish population and G allele
      might be involved in early development of SLE. No association with clinical
      features was found for polymorphism of the promoter region in CTLA-4 +49.

PMID- 19602001
TI  - Filaggrin null mutations in childhood atopic dermatitis among the Chinese.
AB  - Atopic dermatitis (AD) is associated with loss or reduced expression of filaggrin
      (FLG). We evaluated five FLG null mutations, namely R501X, 2282del4, R2447X,
      S2554X, and S2889X, in 174 Chinese children with AD and 191 matched controls.
      2282del4, R2447X, S2554X and S2889X mutations were not found in these patients.
      Heterozygous carriage of R501X was only found in four male patients, and
      associated with long-term disease severity. FLG mutations prevalent in Caucasian
      and other Asian populations are rarely found in our series.

PMID- 19602002
TI  - Editorial comments to Comparison of photoselective vaporization and standard
      transurethral resection of the prostate on urodynamics in patients with benign
      prostatic hyperplasia.

PMID- 19602003
TI  - Comparison of photoselective vaporization and standard transurethral resection of
      the prostate on urodynamics in patients with benign prostatic hyperplasia.
AB  - OBJECTIVES: To compare photoselective vaporization of the prostate (PVP) and
      transurethral resection of the prostate (TURP) in patients with benign prostatic
      hyperplasia. METHODS: Patients were enrolled in a prospective non-randomized
      trial and underwent PVP (n = 78) and TURP (n = 51). Primary outcome variables
      included: International Prostate Symptom Score, quality-of-life score, urinary
      peak flow and post-void residual urine volume at 3, 6 and 12 months
      postoperatively. Secondary outcomes were urodynamic variables, including the
      index of bladder outlet obstruction (BOO) and detrusor contractility. RESULTS:
      Improvement in all outcome variables after PVP was comparable to that after TURP
      within 12 months. Outcome based on urodynamic parameters was also similar.
      Pre/post median value of the BOO index was 63/2 in the PVP group and 61/5 in the
      TURP group. Pre/post rate of detrusor overactivity was 49%/27% in the PVP and
      53%/29% in the TURP group. There was minimal change in detrusor contractility.
      Overall, morbidity was comparable in the two groups. CONCLUSIONS: The 12-month
      outcome after PVP is similar to that of TURP with an effective relief from BOO
      and detrusor overactivity and minimal change in detrusor contractility.

PMID- 19602004
TI  - Perineural invasion is a prognostic factor for biochemical failure after radical
      prostatectomy.
AB  - OBJECTIVES: To identify the prognostic significance of lymphovascular invasion
      (LVI) and perineural invasion (PNI) in patients undergoing radical prostatectomy
      for prostate cancer. METHODS: Overall, 237 patients who had undergone radical
      prostatectomy for prostate cancer between 1995 and 2004 were analyzed for all
      clinical and pathological factors. The influence of these two pathological
      features on biochemical failure-free survival was evaluated by univariate and
      multivariate analysis. RESULTS: Lymphovascular and perineural invasion were
      identified in 41 (17.2%) and 100 (42.0%) patients, respectively. LVI and PNI were
      significantly associated with the preoperative prostate-specific antigen (PSA)
      level, a higher PSA density, a higher pathological stage, a higher Gleason score,
      a higher frequency of extracapsular extension, a higher frequency of seminal
      vesicle invasion, and a higher frequency of a positive resection margin. Positive
      resection margins (P = 0.001) and perineural invasion (P = 0.011) were identified
      as independent factors associated with biochemical failure-free survival by the
      multivariate analysis. CONCLUSIONS: In this series, PNI was associated with
      established parameters of biologically aggressive disease, and was an important
      prognostic factor for biochemical failure-free survival in patients undergoing
      radical prostatectomy. This finding supports routine evaluation of the PNI status
      in radical prostatectomy specimens and suggests that patients with PNI should be
      more closely followed after surgery.

PMID- 19602005
TI  - Evaluation of docetaxel plus estramustine in the treatment of patients with
      hormone-refractory prostate cancer.
AB  - OBJECTIVES: To investigate the feasibility and efficacy of docetaxel-based
      chemotherapy in patients with hormone-refractory prostate cancer (HRPC). METHODS:
      Forty-six consecutive HRPC patients treated between January 2003 and March 2008
      were included in this analysis. Docetaxel was given at a dose of 35 mg/m(2) twice
      every 3 weeks and oral estramustine concurrently for three consecutive days
      during weeks 1 and 2 of each cycle. During each treatment week, the dose of
      estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on
      the third day. Patients were premedicated with 4 mg twice a day of oral
      dexamethasone for three consecutive days. Treatment was continued until evidence
      of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA)
      levels were evaluated at least once every 4 weeks. RESULTS: Patients received a
      median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%)
      had a >or=50% PSA decline and 12 (26%) had a >or=75% PSA decline. Median time to
      PSA progression and overall survival time were 10.1 and 27.0 months,
      respectively. Median follow-up was 15.0 months. Major severe toxicities were
      grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1
      or 2 nausea in eight (17%) patients. Two patients could not continue the
      treatment because of interstitial pneumonitis and a gastric hemorrhage,
      respectively. CONCLUSIONS: Docetaxel plus estramustine chemotherapy represents an
      active and well tolerated treatment for Japanese HRPC patients.

PMID- 19602006
TI  - Obesity does not increase the risk of lymph node metastases in patients with
      clinically localized prostate cancer undergoing radical prostatectomy and
      extended pelvic lymph node dissection.
AB  - OBJECTIVES: Several studies have shown that obesity is associated with more
      aggressive prostate cancer (PCa) variants. We hypothesized that obesity,
      quantified as body mass index (BMI), is associated with a higher risk of lymph
      node invasion (LNI) in patients undergoing extended pelvic lymph node dissection
      (ePLND). METHODS: Clinical and pathological data were available for 994
      consecutive men with PCa treated with radical prostatectomy (RP) and ePLND at a
      single European tertiary academic centre. Univariable and multivariable logistic
      regression analyses addressed the rate of LNI. Covariates consisted of pre
      treatment prostate specific antigen (PSA), biopsy Gleason sum, clinical stage
      history of diabetes mellitus as well as BMI coded as either continuous or
      categorized (<25, 25.0-29.9, 30 kg/m(2) or more) variable. Predictive accuracy
      was assessed with area under curve estimates. RESULTS: Overall LNI was diagnosed
      in 105 patients (10.6%). Mean number of removed lymph nodes was 18.3 (range 7
      60). Of all 994 patients, 372 (37.4%) were normal weight, 518 (52.1%) overweight,
      and 104 (10.5%) were clinically obese. Prevalence of LNI did not significantly
      differ across different BMI categories (<25, 25.0-29.9 and 30 kg/m(2) or more;
      9.9, 10.6 and 12.5%, respectively; P = 0.75). In logistic regression models,
      neither continuously coded nor categorized BMI was a significant predictor of LNI
      at univariable or multivariable analyses (all P-values >or=0.1). Moreover,
      inclusion of BMI with PSA, clinical stage, biopsy Gleason sum and presence of DM
      did not increase the ability of these variables to predict LNI (82.2% without BMI
      vs 82.5% and 82.9% with BMI coded as continuous and categorized variable,
      respectively; all P >or= 0.4). CONCLUSIONS: In men undergoing RP and ePLND,
      increased BMI was not associated with increased risk of lymph node metastases.
      Therefore, routinely considering patient BMI in risk stratification schemes or
      prognostic LNI models may not be warranted.

PMID- 19602007
TI  - Failing to achieve a nadir prostate-specific antigen after combined androgen
      blockade: predictive factors.
AB  - OBJECTIVES: To determine the optimal cut-off of a nadir prostate-specific antigen
      (PSA) for prediction of progression within 24 months after combined androgen
      blockade (CAB) and to analyze predictive factors of failing to achieve the nadir
      PSA. METHODS: We retrospectively reviewed the medical records of 343 patients
      with prostate cancer treated with CAB from 2000 to 2005. We determined the nadir
      PSA level that predicts progression to hormone refractory prostate cancer (HRPC)
      at 24 months after CAB. Predictive factors for failing to achieve a determined
      nadir PSA were analyzed. RESULTS: Mean age was 74.0 years. Mean follow up was
      42.1 month. Seventy-seven patients experienced progression to HRPC. A nadir PSA
      of 1.0 ng/mL predicts progression to HRPC at 24 months. Predictive factors for
      failing to achieve a nadir PSA of 1.0 ng/mL or less include pretreatment PSA,
      percentage positive biopsy core, Gleason score, serum hemoglobin, stage, and
      extent of bone metastasis in univariate analysis. Pretreatment PSA (>50 ng/mL)
      and serum hemoglobin (<12 g/dL) were significant factors to predict failing to
      achieve a nadir PSA of 1.0 ng/mL or less in logistic regression analysis.
      CONCLUSIONS: A nadir PSA of 1.0 ng/mL can predict progression to HRPC after CAB.
      Pretreatment PSA and serum hemoglobin are significant predictors of failing to
      achieve a nadir PSA of 1.0 ng/mL or less.

PMID- 19602008
TI  - Effect of nicotine on the pelvic afferent nerve activity and bladder pressure in
      rats.
AB  - OBJECTIVES: To record afferent nerve activity and bladder pressure in
      anesthetized male rats and to investigate whether increased afferent nerve
      activity induced by nicotine is able to evoke reflex bladder contractions.
      METHODS: Using continuous infusion cystometrography, bladder pressure was
      measured via a bladder cannula. Afferent activity was recorded in the uncut L6
      dorsal root. Nicotine was injected intra-arterially through a cannula placed near
      the bifurcation of the internal iliac artery a few minutes after micturition.
      RESULTS: Nicotine (0.15-1.5 micromol) evoked a marked elevation of afferent
      discharge without a simultaneous increase in bladder pressure. Bladder
      contractions appeared about 43 and 19 s after bolus injection of nicotine at 0.45
      and 1.5 micromol, respectively. Firing rates of afferent nerves were reduced when
      the contraction appeared. Continuous infusion of nicotine at 0.75 micromol/min
      for 20 min evoked marked elevation of afferent discharge, which was maintained
      during infusion of nicotine and after it had been withdrawn. Repetitive
      contractions were observed thereafter and disappeared when the L6 dorsal roots
      were bilaterally resected. CONCLUSIONS: A transient increase in afferent
      discharges induced by bolus injection of nicotine was unable to evoke reflex
      bladder contraction. Repetitive bladder contractions after withdrawal of
      continuous nicotine infusion were induced in a reflex manner by the increased
      afferent activity.

PMID- 19602009
TI  - Cultural variation in nursing: opportunities and challenges.

PMID- 19602011
TI  - First-time mothers and changes in personality in relation to mode of delivery.
AB  - AIM: This paper is a report of a study conducted to examine changes in
      personality from late pregnancy to early motherhood in primiparas having vaginal
      or caesarean deliveries. BACKGROUND: Birth of the first child is a major life
      event, possibly influencing personality. The physiological and emotional
      processes that start in pregnant women have a major impact on the evolving mother
      child relationship. Knowledge about changes in personality during pregnancy and
      motherhood is scarce. METHOD: A prospective, group-comparative cohort study
      including 314 healthy primiparas having either 'caesarean section on maternal
      request' (n = 74) or 'spontaneous vaginal delivery group' (n = 240). The self
      report inventory Karolinska Personality Scales was mailed to participants at 37
      39 gestational weeks in pregnancy and 9 months after delivery. Data were
      collected from January 2003 to June 2006. RESULTS: All mean values of the
      personality variables were within the normal range. There was a statistically
      significant increase in Impulsivity (P = 0.046) and decrease in Socialization (P
      = 0.004). The scores developed differently depending on mode of delivery. Thus,
      women in the vaginal delivery group increased their scores on the Psychic anxiety
      and Guilt scales, while those in the caesarean delivery group decreased their
      scores. Although women in both groups became more impulsive and less socialized,
      personality remained comparatively stable in the transition from late pregnancy
      to motherhood. CONCLUSION: As interactive therapeutic midwife/client
      relationships and maternal/social role preparation have been shown to have a
      great effect on progress in becoming a mother, knowledge about how personality
      may affect this process is important so that healthcare professionals can attempt
      to reduce women's anxiety levels during pregnancy.

PMID- 19602012
TI  - Creating context for critical thinking in practice: the role of the preceptor.
AB  - AIM: This paper is a report of a study to determine the impact of the preceptor
      coaching component of a reflective contextual learning intervention on novice
      nurses' critical thinking skills during the first 6 months of their practice.
      BACKGROUND: The use of preceptors to develop novice nurses' clinical skills has
      been well documented in the literature. However, there is little literature
      focused on preceptor involvement to develop novice nurses' critical thinking.
      METHOD: This small case study was conducted in the United States of America in
      2004 with six nurse/preceptor dyads. Stake's qualitative instrumental case study
      design was used to evaluate the preceptor component of the contextual learning
      intervention. Stories of preceptor experiences were analyzed using Stake's phases
      of data analysis (i.e. description, categorical aggregation, establishing
      patterns, naturalistic generalizations). Specific questions (e.g. nature of
      coaching used by the preceptor) guided the analysis. Repeating patterns were
      coded and isolated and later collapsed as the analysis moved forward. FINDINGS:
      Preceptors use of the contextual learning intervention created a context that
      stimulated novice nurses' critical thinking. Two main themes describe the novice
      nurses' critical thinking skills relative to the preceptor coaching: 1) critical
      thinking as organizing and carrying out tasks; and 2) critical thinking as
      intentional, reflective thinking. CONCLUSION: Preceptor education should
      incorporate the following components: understanding the impact of power and
      anxiety on critical thinking of novice nurses transitioning into practice;
      creating dialogue that invites questions in a reflective and critical manner; and
      challenging thinking through sharing of perspectives.

PMID- 19602013
TI  - In response to: Burkhart P.V., Svavarsdottir E.K., Rayens M.K., Oakley M.G.,
      Orlygsdottir B. (2009) Adolescents with asthma: predictors of quality of life.
      Journal of Advanced Nursing 65(4), 860-866.

PMID- 19602014
TI  - In response to: Anthony, S. & Jack, S. (2009) Qualitative case study methodology
      in nursing research: an integrative review. Journal of Advanced Nursing 65(6),
      1171-1181.

PMID- 19602017
TI  - Coronary angiography is a simple and reliable method to identify which aortic
      cusp is being mapped.

PMID- 19602015
TI  - The microbial signature of aerosols produced during the thermophilic phase of
      composting.
AB  - AIMS: The microbial diversity of bioaerosols released during operational
      activities at composting plants is poorly understood. Identification of bacteria
      and fungi present in such aerosols is the prerequisite for the definition of
      microbial indicators that could be used in dispersal and exposure studies.
      METHODS AND RESULTS: A culture-independent analysis of composting bioaerosols
      collected at five different industrial open sites during the turning of
      composting piles in fermentation was performed by building 16S rDNA and 18S rDNA
      libraries. More than 800 sequences were analysed. Although differences in the
      phylotypes distribution were observed from one composting site to another,
      similarities in the structure of microbial diversity were remarkable. The same
      phyla dominated in the five bioaerosols: Ascomycota among fungi, Firmicutes and
      Actinobacteria among bacteria. For each phylum, some dominant phylotypes were
      common to at least four bioaerosols. These common phylotypes belonged to
      Thermomyces, Aspergillus, Penicillium, Geobacillus, Planifilum,
      Thermoactinomyces, Saccharopolyspora, Thermobifida and Saccharomonospora.
      CONCLUSIONS: The microbial signature of aerosols produced during the thermophilic
      phase of composting was determined. The similarities observed may be explained by
      the selection of thermophilic and sporulating species. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Several bacteria and fungi identified in this study may represent
      potential indicators of composting bioaerosols in air.

PMID- 19602018
TI  - Cryoballoon pulmonary vein isolation with real-time recordings from the pulmonary
      veins.
AB  - INTRODUCTION: Cryoballoon (CB) ablation represents a novel technology for
      pulmonary vein isolation (PVI). We investigated feasibility and safety of CB-PVI,
      utilizing a novel spiral catheter (SC), thereby obtaining real-time PV potential
      registration. METHODS: Following double transseptal puncture, a Lasso catheter
      (Biosense Webster, Diamond Bar, CA, USA) and the 28 mm CB were positioned within
      the left atrium. A novel SC (Promap, ProRhythm Inc., Ronkonkoma, NY, USA) was
      inserted through the lumen of the CB allowing PV signal registration during
      treatment. Time to PV conduction block was analyzed. If no stable balloon
      position was obtained, the SC was exchanged for a regular guide wire and PV
      conduction was assessed after treatment by Lasso catheter. RESULTS: In 18
      patients, 39 of 72 PVs (54%) were successfully isolated using the SC. The
      remaining 33 PVs were isolated switching to the regular guide wire. Time to PV
      conduction block was significantly shorter in PVs in which sustained PVI was
      achieved as compared to PVs in which PV conduction recovered within 30 minutes
      (33 +/- 21 seconds vs 99 +/- 65 seconds). In 40 PVs, time to PV conduction block
      was not obtained because of: (1) PVI not being achieved during initial treatment;
      (2) a distal position of the SC; or (3) isolation with regular guide wire. No
      procedural complications occurred. CONCLUSION: Visualization of real-time PV
      conduction during CB PVI is safe, feasible, and allows accurate timing of PVI
      onset in a subset of PVs. Time to PV conduction block predicts sustained PVI.
      However, mechanical properties of the SC need to be improved to further simplify
      CB PVI.

PMID- 19602019
TI  - Electrical storm after CRT implantation treated by AV delay optimization.
AB  - We present a case of symptomatic ischemic heart failure with an indication for
      cardiac resynchronization and implantable cardiac defibrillator therapy in
      primary prevention. After implantation, the patient developed a severe electrical
      storm with multiple shocks. Hemodynamic improvement based only on AV delay,
      guided by echocardiography and ECG, brought about a dramatic improvement in the
      situation. We discuss the pathophysiology of electrical storm occurring
      immediately after LV pacing.

PMID- 19602020
TI  - Interatrial mechanical dyssynchrony worsened atrial mechanical function in sinus
      node disease with or without paroxysmal atrial fibrillation.
AB  - INTRODUCTION: Atrial electromechanical dysfunction might contribute to the
      development of atrial fibrillation (AF) in patients with sinus node disease
      (SND). The aim of this study was to investigate the prevalence and impact of
      atrial mechanical dyssynchrony on atrial function in SND patients with or without
      paroxysmal AF. METHODS: We performed echocardiographic examination with tissue
      Doppler imaging in 30 SND patients with (n = 11) or without (n = 19) paroxysmal
      AF who received dual-chamber pacemakers. Tissue Doppler indexes included atrial
      contraction velocities (Va) and timing events (Ta) were measured at midleft
      atrial (LA) and right atrial (RA) wall. Intraatrial synchronicity was defined by
      the standard deviation and maximum time delay of Ta among 6 segments of LA
      (septal/lateral/inferior/anterior/posterior/anterospetal). Interatrial
      synchronicity was defined by time delay between Ta from RA and LA free wall.
      RESULTS: There were no differences in age, P-wave duration, left ventricular
      ejection fraction, LA volume, and ejection fraction between with or without AF.
      Patients with paroxysmal AF had lower mitral inflow A velocity (70 +/- 19 vs 91
      +/- 17 cm/s, P = 0.005), LA active empting fraction (24 +/- 14 vs 36 +/- 13%, P =
      0.027), mean Va of LA (2.6 +/- 0.9 vs 3.4 +/- 0.9 cm/s, P = 0.028), and greater
      interatrial synchronicity (33 +/- 25 vs 12 +/- 19 ms, P = 0.022) than those
      without AF. Furthermore, a lower mitral inflow A velocity (Odd ratio [OR]= 1.12,
      95% Confidence interval [CI] 1.01-1.24, P = 0.025) and prolonged interatrial
      dyssynchrony (OR = 1.08, 95% CI 1.01-1.16, P = 0.020) were independent predictors
      for the presence of AF in SND patients. CONCLUSION: SND patients with paroxysmal
      AF had reduced regional and global active LA mechanical contraction and increased
      interatrial dyssychrony as compared with those without AF. These findings suggest
      that abnormal atrial electromechanical properties are associated with AF in SND
      patients.

PMID- 19602021
TI  - The impact of left atrial size on long-term outcome of catheter ablation of
      chronic atrial fibrillation.
AB  - BACKGROUND: The left atrial (LA) size is an important predictor of atrial
      fibrillation (AF) procedural termination and the long-term outcome. We sought to
      evaluate the long-term outcome in regard to the LA size and procedural
      termination. METHODS: Eighty-seven consecutive chronic AF patients (72 males, 53
      +/- 10 years) underwent 3D mapping (NavX) and ablation. A stepwise approach
      including circumferential pulmonary vein (PV) isolation, linear ablation, and
      continuous complex-fractionated electrogram (CFE) ablation (targeting
      fractionation intervals of < 50 ms). Electrical cardioversion was applied to
      those without any procedural termination. The freedom from AF was defined as the
      maintenance of sinus rhythm without the use of any class I or III antiarrhythmic
      drugs after the blanking period. RESULTS: Among the 87 patients, all received a
      circumferential PV isolation, 93% a linear ablation, and 59% a continuous CFE
      ablation. Those with AF procedural termination (n = 30) had a better long-term
      outcome when compared with those without termination during a follow-up of 21 +/-
      12 months. Moreover, a Kaplan-Meier analysis showed that in those with an LA
      diameter of less than 45 mm (n = 49), the freedom from AF rate was higher when
      procedural termination was achieved (P = 0.004). On the contrary, the outcome was
      comparable in those with an LA diameter of >or= 45 mm (n = 38), whether AF
      procedural termination occurred or not (P = 0.658). CONCLUSIONS: AF procedural
      termination was related to the long-term success during chronic AF ablation,
      especially in those with an LA diameter of less than 45 mm. The favorable effect
      of termination decreased when the LA diameter was >or= 45 mm.

PMID- 19602022
TI  - Percutaneous microwave ablation with a long side-firing antenna array can
      successfully treat a nonsurgical chronic ovine atrial flutter model.
AB  - INTRODUCTION: Long side-firing microwave (MW) arrays can deliver energy uniformly
      over its length without the need for intimate endocardial contact. We hypothesize
      that a novel 6 Fr 20 mm long percutaneous high-efficiency MW antenna array
      ablation catheter can rapidly create long, continuous, and transmural linear
      ablation lesions. METHODS AND RESULTS: Cavotricuspid isthmus (CTI)-dependent
      atrial flutter (AFL) was created in 11 sheep by a line of radiofrequency ablation
      lesions in the posterior right atrium (RA) linking the venae cavae. After 4-6
      weeks recovery, CTI-dependent AFL was still inducible in all 11 sheep (cycle
      length 178 +/- 13 ms). MW ablation of the CTI at 100 W for 30 seconds was then
      performed with an endpoint of AFL noninducibility. AFL was not inducible in all
      11 sheep after 4.3 +/- 3.3 MW applications (129 +/- 99 seconds). The last 6
      animals needed fewer ablations (2.2 +/- 1.5) and 3 of these sheep required only a
      single ablation. Although conduction times from proximal coronary sinus to
      lateral RA and vice versa increased postablation (51 +/- 14 ms to 118 +/- 31 ms
      [P = 0.0002] and 60 +/- 13 ms to 119 +/- 28 ms [P = 0.0001], respectively), AFL
      was still inducible in 2 sheep and further ablation was needed to reach the
      endpoint. CONCLUSIONS: High-efficiency side-firing MW array ablation can rapidly
      create long linear and electrically intact lesions in an ovine AFL model. AFL
      noninducibility may be a more reliable indicator than CTI conduction times of an
      intact line of ablation in this animal model.

PMID- 19602023
TI  - Percutaneous epicardial radiofrequency ablation of ventricular arrhythmias after
      failure of endocardial approach: a 9-year experience.
AB  - INTRODUCTION: Management of recurrent ventricular tachycardia (VT) remains
      difficult. Neither medical treatments nor conventional endocardial radiofrequency
      (RF) ablation are efficient to prevent some recurrences. In these cases, a
      percutaneous pericardial approach may be required. METHODS: Among all the
      patients referred to our center between 1998 and 2007 for a VT ablation, 276
      endocardial and 35 epicardial procedures were performed, the latter in case of
      failure of the conventional approach. We report in this study the efficacy and
      the safety of these 35 interventions analyzed retrospectively. RESULTS: Thirty
      five epicardial procedures were attempted in 32 patients. An electric storm was
      present in 5 of 32 (16%) patients, with other individuals presenting with a
      recurrent VT despite drug therapy and a previous endocardial ablation.
      Pericardial space was reached in 28 of 32 patients by a xyphoidian puncture. An
      immediate success of RF on clinical VT was obtained in 22 of 29 (76%) cases.
      During a mean follow-up of 384 +/- 405 days, only 9 patients (26%) experienced a
      recurrence of a sustained VT. One patient died from tamponade during the
      procedure despite surgical drainage. Other complications had no significant
      consequences. CONCLUSION: Percutaneous epicardial puncture is feasible and
      relatively safe in patients with recurrent VT in whom conventional endocardial RF
      ablation failed. Epicardial RF ablation offers a high success rate in these
      challenging patients with only few severe complications.

PMID- 19602024
TI  - Home monitoring in patients with implantable cardiac devices: is there a
      potential reduction of stroke risk? Results from a computer model tested through
      monte carlo simulations.
AB  - INTRODUCTION: Patients with pacemakers and implantable defibrillators (ICD) may
      experience asymptomatic atrial fibrillation (AF), detected with a delay depending
      on the in-person follow-up schedule. Home monitoring (HM) remote control with
      automatic alerts for AF may drive early anticoagulation, potentially reducing
      stroke risk. METHODS AND RESULTS: A sample of 136 pacemaker (103) and ICD (33)
      patients with or without cardiac resynchronization therapy not taking
      anticoagulation at implant were monitored remotely with HM. Upon HM alerts for
      AF, patients were recalled to update therapy. Two-year data were entered in a
      computer Monte Carlo model, simulating 4,000 virtual subjects with the same AF
      and CHADS(2) stroke risk distribution of our real population. Simulations
      reproduced a 2-year follow-up. Two thousand subjects were supposed to be followed
      with HM (HM group) and 2,000 with standard in-person follow-up (SF group) at 3,
      6, 9, or 12 months. Two-year Kaplan-Meier cumulative probability of >/=24-hour AF
      was 15.6% (95%CI 8.5-23.3%); the AF-related symptom rate was 27% and the median
      CHADS(2) score was 2. As a result of simulations, stroke incidence in case of AF
      was 2.3 +/- 1.1% in the HM group and 2.4 +/- 1.1%, 2.5 +/- 1.2%, 2.7 +/- 1.2%,
      and 2.9 +/- 1.3% in the SF group with 3-, 6-, 9-, and 12-month follow-up
      programs, with odds ratios of 0.97 (95%CI 0.93-1.01), 0.91 (0.88-0.95), 0.87
      (0.84-0.90), and 0.82 (0.79-0.85) (HM better if odds ratios <1), respectively.
      CONCLUSIONS: Daily HM potentially reduces the stroke risk by 9% to 18% with
      respect to SF with intervisit intervals of 6 to 12 months.

PMID- 19602025
TI  - Prevention of thromboembolic stroke in patients undergoing catheter-based
      ablation for atrial fibrillation: has it been optimized?

PMID- 19602026
TI  - Postoperative atrial flutter: circuit in the right or left atrium?

PMID- 19602027
TI  - The relationship between endocardial voltage and regional volume in
      electroanatomical remodeled left atria in patients with atrial fibrillation:
      comparison of three-dimensional computed tomographic images and voltage mapping.
AB  - BACKGROUND: Long-standing atrial fibrillation (AF) changes left atrial (LA)
      morphology, and the LA size is related to recurrence after radiofrequency
      catheter ablation (RFCA). We hypothesize that LA morphology, based on
      embryological origin, affects the outcome of RFCA. METHODS: We analyzed 3D
      computed tomographic (CT) images of LA in 70 patients with AF (54 males, 55.6 +/-
      10.5 years old, paroxysmal AF (PAF):persistent AF (PeAF) = 32:38) who underwent
      RFCA. Each LA image was divided into venous atrium (VA), anterior LA (ALA), LA
      appendage (LAA), and both antrum. Absolute and relative volumes were calculated,
      and the lengths of linear ablation sites were measured. RESULTS: (1) In patients
      with the mean LA voltage < or = 2.0 mV, LA volume, especially ALA, was larger (P
      < 0.01) compared to those with LA voltage > 2.0 mV. (2) The total LA volume was
      significantly larger (P < 0.01) and LAA voltages (P < 0.05) and conduction
      velocities (P < 0.05) were lower in patients with PeAF than in those with PAF.
      (3) In patients with recurrence, LA volume was generally larger (P < 0.01) than
      in those without recurrence. In PAF patients with recurrence, the relative volume
      of ALA was significantly larger (P < 0.01) than those without recurrence.
      CONCLUSIONS: Morphologically remodeled LA has low endocardial voltage, and
      enlargement of ALA is more significant in electroanatomically remodeled LA. The
      disproportional enlargement of ALA was observed more often in PAF patients with
      recurrence after ablation than those without recurrence.

PMID- 19602028
TI  - Synchronous ventricular pacing without crossing the tricuspid valve or entering
      the coronary sinus--preliminary results.
AB  - BACKGROUND: Right ventricular apical (RVA) pacing promotes tricuspid
      regurgitation (TR), electromechanical dyssynchrony, and ventricular dysfunction.
      We tested a novel intramyocardial bipolar lead to assess whether stimulation of
      the atrioventricular septum (AVS) produces synchronous ventricular activation
      without crossing the tricuspid valve (TV). METHODS: A lead with an active
      external helix and central pin was placed on the AVS and the RVA in three dogs.
      High-density electroanatomic (EA) mapping was performed of both ventricles
      endocardially and epicardially. Intracardiac echocardiography was used to access
      ventricular synchrony. RESULTS: The lead was successfully deployed into the AVS
      in all cases with consistent capture of the ventricular myocardium without atrial
      capture or sensing. The QRS duration was less with AVS compared with RVA pacing
      (89 +/- 4 ms vs. 100 +/- 11 ms [P < 0.0001, GEE P = 0.03]). There was decreased
      delay between color Doppler M-mode visualized peak contraction of the septum and
      the mid left ventricular free wall with AVS compared with RVA pacing (89 +/- 91
      ms vs. 250 +/- 11 ms [P < 0.0001, GEE P = 0.006]). Activation time between the
      mid septum and mid free wall was shorter with AVS versus RVA pacing (20.4 +/- 7.7
      vs. 30.8 +/- 11.6 [P = 0.01, GEE P = 0.07]). The interval between QRS onset to
      earliest free wall activation was shorter with AVS vs. RVA pacing (19.2 +/- 6.4
      ms vs. 31.1 +/- 11.7 ms [P = 0.005, GEE P = 0.02]). CONCLUSION: The AVS was
      successfully paced in three dogs resulting in synchronous ventricular activation
      without crossing the TV.

PMID- 19602029
TI  - Is performance of routine transesophageal echocardiography justified prior to
      catheter ablation for atrial fibrillation?

PMID- 19602030
TI  - Scar-related right ventricular tachycardia: part of the spectrum of
      arrhythmogenic right ventricular cardiomyopathy?

PMID- 19602031
TI  - Time to cardioversion of recurrent atrial arrhythmias after catheter ablation of
      atrial fibrillation and long-term clinical outcome.
AB  - INTRODUCTION: It is unclear whether early restoration of sinus rhythm in patients
      with persistent atrial arrhythmias after catheter ablation of atrial fibrillation
      (AF) facilitates reverse atrial remodeling and promotes long-term maintenance of
      sinus rhythm. The purpose of this study was to determine the relationship between
      the time to restoration of sinus rhythm after a recurrence of an atrial
      arrhythmia and long-term maintenance of sinus rhythm after radiofrequency
      catheter ablation of AF. METHODS AND RESULTS: Radiofrequency catheter ablation
      was performed in 384 consecutive patients (age 60 +/- 9 years) for paroxysmal
      (215 patients) or persistent AF (169 patients). Transthoracic cardioversion was
      performed in all 93 patients (24%) who presented with a persistent atrial
      arrhythmia: AF (n = 74) or atrial flutter (n = 19) at a mean of 51 +/- 53 days
      from the recurrence of atrial arrhythmia and 88 +/- 72 days from the ablation
      procedure. At a mean of 16 +/- 10 months after the ablation procedure, 25 of 93
      patients (27%) who underwent cardioversion were in sinus rhythm without
      antiarrhythmic therapy. Among the 46 patients who underwent cardioversion at < or
      =30 days after the recurrence, 23 (50%) were in sinus rhythm without
      antiarrhythmic therapy. On multivariate analysis of clinical variables, time to
      cardioversion within 30 days after the onset of atrial arrhythmia was the only
      independent predictor of maintenance of sinus rhythm in the absence of
      antiarrhythmic drug therapy after a single ablation procedure (OR 22.5; 95% CI
      4.87-103.88, P < 0.001). CONCLUSION: Freedom from AF/flutter is achieved in
      approximately 50% of patients who undergo cardioversion within 30 days of a
      persistent atrial arrhythmia after catheter ablation of AF.

PMID- 19602032
TI  - First in human validation of impedance-based catheter tip-to-tissue contact
      assessment in the left atrium.
AB  - BACKGROUND: In this study, a new method of contact assessment based on the
      measurement of the local electrical properties at the catheter tip-to-tissue
      interface was validated in a blinded fashion in vivo in the human left atrium.
      METHODS: Using a 3-terminal circuit model, local resistance and reactance between
      catheter tip and tissue surface were measured and combined in an electrical
      coupling index (ECI). Twelve patients undergoing atrial fibrillation (AF)
      catheter ablation were included in this study. The catheter was placed in the
      left atrium at various levels of contact. Blinded to the physician, measurements
      of electrogram amplitudes, pacing thresholds, and impedances at the catheter tip
      to-tissue interface were performed. RESULTS: As the catheter went from noncontact
      to contact, ECI increased from 118 +/- 15 to 145 +/- 24 (P < 0.0001), electrogram
      amplitudes increased from 0.14 +/- 0.16 to 2.0 +/- 1.9 mV (P < 0.0001), and
      pacing thresholds decreased from 13.9 +/- 3.1 to 3.1 +/- 2.0 mA (P < 0.0001). ECI
      was significantly higher in vascular tissue as compared with trabeculated and
      smooth myocardium. Patch orientation, operator, body mass index, or clinical type
      of AF had no influence on ECI values. On a patient-by-patient analysis, true
      contact/noncontact locations showed a mean ECI difference of 32.7 +/- 11.6 units
      (95% CI 25.8-39.6). A cut-off value of 5 ECI units was able to separate contact
      from noncontact with 97% sensitivity and 95% specificity. CONCLUSION: Measurement
      of local impedances between catheter tip and tissue is feasible to reproducibly
      describe electrical catheter contact within the left atrium in a clinical setting
      of AF catheter ablation.

PMID- 19602033
TI  - Clinical relevance and functional implications for human leucocyte antigen-g
      expression in non-small-cell lung cancer.
AB  - HLA-G has been documented both in establishment of anti-tumour immune responses
      and in tumour evasion. To investigate the clinical relevance of HLA-G in non
      small-cell lung cancer (NSCLC), expression status and potential significance of
      HLA-G in NSCLC were analysed. In this study, HLA-G expression in 101 NSCLC
      primary lesions and plasma soluble HLA-G (sHLA-G) from 91 patients were analysed
      with immunohistochemistry and ELISA, respectively. Correlations between HLA-G
      status and various clinical parameters including survival time were evaluated.
      Meanwhile, functional analysis of transfected cell surface HLA-G expression and
      plasma sHLA-G form NSCLC patients on natural killer (NK) cell cytolysis were
      performed. Data revealed that HLA-G was expressed in 41.6% (42/101) NSCLC primary
      lesions, while undetectable in adjacent normal lung tissues. HLA-G expression in
      NSCLC lesions was strongly correlated to disease stages (P= 0.002). Plasma sHLA-G
      from NSCLC patients was markedly higher than that in normal controls (P= 0.004),
      which was significantly associated with the disease stages (I versus IV, P=
      0.025; II versus IV, P= 0.029). Patient plasma sHLA-G level (>=median, 32.0 U/ml)
      had a significantly shorter survival time (P= 0.044); however, no similar
      significance was observed for the lesion HLA-G expression. In vitro data showed
      that both cell surface HLA-G and patient plasma sHLA-G could dramatically
      decrease the NK cell cytolysis. Our findings indicated that both lesion HLA-G
      expression and plasma sHLA-G in NSCLC is related to the disease stage and can
      exert immunosuppression to the NK cell cytolysis, indicating that HLA-G could be
      a potential therapeutic target. Moreover, plasma sHLA-G in NSCLC patients could
      be used as a prognosis factor for NSCLC.

PMID- 19602035
TI  - EORTC trial 11001: distribution of two 10B-compounds in patients with squamous
      cell carcinoma of head and neck, a translational research/phase 1 trial.
AB  - Boron neutron capture therapy (BNCT) provides highly targeted delivery of
      radiation through the limited spatial distribution of its effects. This
      translational research/phase I clinical trial investigates whether BNCT might be
      developed as a treatment option for squamous cell carcinoma of head and neck
      (SCCHN) relying upon preferential uptake of the two compounds, sodium
      mercaptoundecahydro-closo-dodecaborate (BSH) or L-para-boronophenylalanine (BPA)
      in the tumour. Before planned tumour resection, three patients received BSH and
      three patients received BPA. The (10)B-concentration in tissues and blood was
      measured with prompt gamma ray spectroscopy. Adverse effects from compounds did
      not occur. After BPA infusion the (10)B-concentration ratio of tumour/blood was
      4.0 +/- 1.7. (10)B-concentration ratios of tumour/normal tissue were 1.3 +/- 0.5
      for skin, 2.1 +/- 1.2 for muscle and 1.4 +/- 0.01 for mucosa. After BSH infusion
      the (10)B-concentration ratio of tumour/blood was 1.2 +/- 0.4. (10)B
      concentration ratios of tumour/normal tissue were 3.6 +/- 0.6 for muscle, 2.5 +/-
      1.0 for lymph nodes, 1.4 +/- 0.5 for skin and 1.0 +/- 0.3 for mucosa. BPA and BSH
      deliver (10)B to SCCHN to an extent that might allow effective BNCT treatment.
      Mucosa and skin are the most relevant organs at risk.

PMID- 19602034
TI  - Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine.
AB  - Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone
      marrow and many other tissues can be easily isolated and expanded in vitro. They
      are capable of differentiating into different cell types such as osteoblasts,
      chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and
      neuronal cells. Such immense plasticity coupled with their ability to modulate
      the activity of immune cells makes them attractive for stem cell-based therapy
      aimed at treating previously incurable disorders. Preclinical studies have
      reported successful use of MSCs for delivering therapeutic proteins and repairing
      defects in a variety of disease models. These studies highlighted the in vivo
      potential of MSCs and their ability to home to injury sites and modify the
      microenvironment by secreting paracrine factors to augment tissue repair. Their
      therapeutic applicability has been widened by genetic modification to enhance
      differentiation and tissue targeting, and use in tissue engineering. Clinical
      trials for diseases such as osteogenesis imperfecta, graft-versus-host disease
      and myocardial infarction have shown some promise, demonstrating the safe use of
      both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour
      and responses in vitro and in vivo force the need for basic and animal studies
      before heading to the clinic. Contrasting reports on immunomodulatory functions
      and tumorigenicity along with issues such as mode of cell delivery, lack of
      specific marker, low survival and engraftment require urgent attention to harness
      the potential of MSC-based therapy in the near future.

PMID- 19602038
TI  - Intraplaque injection of Ad5-CMV.p53 aggravates local  inflammation and leads to
      plaque instability in rabbits.
AB  - This study aims to develop a new animal model of vulnerable plaques and
      investigate the potential mechanisms of exogenous p53-induced plaque instability.
      Forty rabbits underwent aortic balloon injury, were fed a 1% cholesterol diet for
      10 weeks and then normal chow for 6 weeks. Rabbits were divided into Ad5-CMV.p53
      treated group (n = 16), Ad5-CMV.lac Z-treated group (n = 16) and blank control
      group (n = 8). Under the guidance of intravascular ultrasound, a 50-microl
      suspension of adenovirus containing p53 or lac Z was injected into the largest
      plaque of the first two groups, respectively, and these rabbits received
      pharmacological triggering 2 weeks later. In 76.9% of rabbits with p53
      transfection, plaque rupture was found, which was significantly (P < 0.05) higher
      than that in the Ad5-CMV.lac Z-treated plaques (23.1%), or blank controls plaques
      (0%). Increased apoptotic cells, and subsequently, decreased vascular smooth
      muscle cells and collagen content, enhanced intima macrophage accumulation,
      increased C-reactive protein (CRP) and matrix metalloproteinases staining and
      high serum levels of high sensitive CRP (hs-CRP) and monocyte chemoattractant
      protein-1 (MCP-1) were observed in Ad5-CMV.p53-treated rabbits. However, a binary
      logistic regression model revealed that hs-CRP concentration rather than
      apoptosis rate played an independent role in plaque rupture with an odds ratio as
      1.314 (95% CI: 1.041-1.657, P = 0.021), and there were high positive correlations
      between inflammatory biomarkers (hs-CRP or MCP-1) and apoptosis (R(2) = 0.761,
      and R(2) = 0.557, respectively, both P < 0.01). Intraplaque injection of p53 gene
      provides a safe and effective method for inducing plaque vulnerability in
      rabbits. The destabilizing effect of p53 overexpression is mediated mainly
      through apoptosis-enhanced inflammation rather than cell apoptosis itself.

PMID- 19602036
TI  - Epigenetic programming of mu-opioid receptor gene in mouse brain is regulated by
      MeCP2 and Brg1 chromatin remodelling factor.
AB  - The pharmacological action of morphine as a pain medication is mediated primarily
      through the mu-opioid receptor (MOR). With few exceptions, MOR is expressed in
      brain regions where opioid actions take place. The basis for this unique spatial
      expression of MOR remains undetermined. Recently, we reported that DNA
      methylation of the MOR promoter plays an important role in regulating MOR in P19
      cells. In this study, we show that the differential expression of MOR in
      microdissected mouse brain regions coincides with DNA methylation and histone
      modifications. MOR expression could be induced by a demethylating agent or a
      histone deacetylase inhibitor in MOR-negative cells, suggesting that the MOR gene
      can be silenced under epigenetic control. Increases in the in vivo interaction of
      methyl-CpG-binding protein 2 (MeCP2) were observed in the cerebellum, in which
      the MOR promoter was hypermethylated and MOR expression was the lowest among all
      brain regions tested. MeCP2 is associated closely with Rett syndrome, a
      neurodevelopmental disorder. We also established novel evidence for a functional
      role for MeCP2's association with the chromatin-remodelling factor Brg1 and DNA
      methyltransferase Dnmt1, suggesting a possible role for MeCP2 in chromatin
      remodelling during MOR gene regulation. We conclude that MOR gene expression is
      epigenetically programmed in various brain regions and that MeCP2 assists the
      epigenetic program during DNA methylation and chromatin remodelling of the MOR
      promoter.

PMID- 19602037
TI  - A prospective study of macrophage migration inhibitory factor as a marker of
      inflammatory detection.
AB  - This study was to evaluate whether macrophage migration inhibitory factor (MIF)
      can be used as a better marker of inflammatory detection through the
      biodistribution and inflammatory imaging study with (131)I-labelled anti-MIF McAb
      and control antibody in inflammatory model mice. The mRNA and protein expression
      of MIF in inflammatory lesions were proved by RT-PCR and immunohistochemistry.
      The model mice were injected with 3.7 MBq of each agent and killed at 24, 48 and
      72 hrs after injection. Whole-body images were obtained with storage phosphor
      screen. The organs, blood, abscesses muscles were removed, weighed and counted
      with a gamma counter. The percentage of uptake by organs and per gram tissues and
      abscess/normal tissue (%ID/g) concentration ratios were calculated. The abscesses
      in mice were well visualized from 24 hrs. The target-to-non-target (T/NT) ratios
      were 6.71 +/- 1.09 (24 hrs), 8.57 +/- 0.81 (48 hrs) and 11.41 +/- 0.37 (72 hrs)
      for (131)I-labelled anti-MIF McAb group; while in control group of (131)I-IgG,
      T/NT ratios were 4.65 +/- 0.63 (24 hrs), 6.44 +/- 0.60 (48 hrs) and 8.23 +/- 0.35
      (72 hrs) (P < 0.05). MIF mRNA expression was threefold increased in inflammatory
      tissues at 24 hrs compared with normal tissues, and twofold increased at 48 hrs.
      MIF protein expression was stronger in the inflammatory tissues at 48 hrs after
      focal inflammation occurred. Our findings suggest that the (131)I-labelled anti
      MIF McAb appears to be more specific and suitable than (131)I-labelled IgG for
      targeting focal inflammation, which means MIF can be used as a better marker of
      inflammatory detection.

PMID- 19602039
TI  - Osteopontin promotes gastric cancer metastasis by augmenting  cell survival and
      invasion through Akt-mediated HIF-1alpha up-regulation and MMP9 activation.
AB  - Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated
      glycoprotein. OPN has been shown to facilitate the progression and metastasis of
      malignancies and has prognostic value in several types of cancer, including
      gastric cancer. However, the functional mechanism of OPN mediated metastatic
      growth in gastric cancer remains unclear. Here, using multiple in vitro and in
      vivo models, we report that OPN strongly promoted the progression and metastasis
      of gastric cancer. Immunohistochemical staining revealed that OPN, matrix
      metalloproteinase (MMP)9 and hypoxia-inducible factor (HIF)-1alpha have
      statistically significant different expression patterns between well- and poorly
      differentiated tissue samples (P < 0.05). Correlations existed between OPN and
      MMP9, and between OPN and HIF-1 (r(1) = 0.872, p(1) < 0.01 and r(2) = 0.878, p(2)
      < 0.01). Furthermore, OPN dramatically increased colony formation and invasion of
      gastric cancer cells in vitro and promoted tumour growth and metastasis in vivo.
      In addition, OPN potently protected gastric cancer cells from serum depletion
      induced apoptosis. Further study shows that OPN activated phosphoinositide 3
      kinase/Akt survival pathway and up-regulated HIF-1alpha via binding to v3
      integrins in gastric cancer cells. Moreover, we found that OPN could activate
      MMP9 and upregulate MMP2. Taken together, our results suggest that the survival
      promoting function is crucial for OPN to promote the development of gastric
      cancer, and HIF-1 and MMP9 may play key roles during this process. Thus,
      targeting OPN and its related signalling network may develop an effective
      therapeutic approach for the management of gastric cancer.

PMID- 19602040
TI  - Let-7 repression leads to HMGA2 overexpression in uterine leiomyosarcoma.
AB  - Overexpression of HMGA2 is common in uterine leiomyomas (ULM). The expression of
      HMGA2 in its malignant counterpart - uterine leiomyosarcomas (ULMS) remains
      undetermined. Recently it has been shown that repression of HMGA2 by microRNA let
      7s is a critical molecular regulatory mechanism associated with tumour growth in
      many tumours and cell types, including leiomyomas. To test whether HMGA2 and let
      7s play a role in ULMS, we examined the levels of endogenous HMGA2 and let-7
      expression and found a significant correlation between these two molecules in a
      case-matched cohort of human ULMS. We found that overexpression of HMGA2 and let
      7-mediated HMGA2 repression is a relevant molecular alteration in ULMS.
      Disrupting the control of HMGA2 and let-7 pairs promotes ULMS cell growth in
      vitro.

PMID- 19602041
TI  - The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and
      immunoregulatory effects.
AB  - The interferon (IFN)-gamma-inducible tryptophan degrading enzyme indoleamine 2,3
      dioxygenase (IDO) has not only been recognized as a potent antimicrobial effector
      molecule for the last 25 years but was recently found also to have potent
      immunoregulatory properties. In this study, we provide evidence that both
      tryptophan starvation and production of toxic tryptophan metabolites are involved
      in the immunoregulation mediated by IDO, whereas tryptophan starvation seems to
      be the only antibacterial effector mechanism. A long-studied controversy in the
      IDO research field is the seemingly contradictory effect of IDO in the defence
      against infectious diseases. On the one hand, IFN-gamma-induced IDO activity
      mediates an antimicrobial effect, while at the same time IDO inhibits T-cell
      proliferation and IFN-gamma production. Here, we suggest that both effects,
      dependent on the threshold for tryptophan, cooperate in a reasonable coherence.
      We found that the minimum concentration of tryptophan required for bacterial
      growth is 10-40-fold higher than the minimum concentration necessary for T-cell
      activation. Therefore, we suggest that during the first phase of infection the
      IDO-mediated tryptophan depletion has a predominantly antimicrobial effect
      whereas in the next stage, and with ongoing tryptophan degradation, the minimum
      threshold concentration of tryptophan for T-cell activation is undercut,
      resulting in an inhibition of T-cell growth and subsequent IDO activation.

PMID- 19602042
TI  - The polyubiquitin Ubc gene modulates histone H2A monoubiquitylation in the R6/2
      mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disease caused by the
      expansion of a polyglutamine tract in the protein huntingtin (htt). HD brains are
      characterized by the presence of ubiquitin-positive neuronal inclusion bodies,
      suggesting that disturbances in the distribution of cellular ubiquitin may
      contribute to disease pathology. The fact that several neurodegenerative diseases
      are caused by mutations in ubiquitin-processing enzymes and that the
      polyubiquitin genes are required for resistance to cellular stress led us to
      investigate the effect of perturbing the ubiquitin system in HD. We crossed R6/2
      transgenic HD mice with heterozygous polyubiquitin Ubc knockout mice (Ubc+/-) and
      assessed the effect on the R6/2 neurological phenotype. Although the R6/2
      phenotype was largely unaffected, surprisingly we observed some subtle
      improvements in various behavioural activities correlating with heterozygous Ubc
      knockout. Interestingly, immunoblot analysis revealed that the levels of
      monoubiquitylated histone H2A (uH2A), a modification associated with gene
      repression, were significantly increased in the brains of R6/2 mice. Furthermore,
      the reduction of Ubc expression in R6/2; Ubc+/- mice largely prevented this
      increase in uH2A levels. However, we were not able to show by the use of a
      limited number of quantitative RT-PCR assays that changes in the amount of uH2A
      in the R6/2-Ubc mice had an effect on disease-associated transcriptional
      abnormalities. These results suggest that the expression of aggregation-prone
      mutant htt causes disturbances to the ubiquitin system, which may contribute to
      disease due to the diverse and important roles of ubiquitin.

PMID- 19602043
TI  - Nutritional channels in breast cancer.
AB  - Breast cancers increase glucose uptake by increasing expression of the
      facilitative glucose transporters (GLUTs), mainly GLUT1. However, little is known
      about the relationship between GLUT1 expression and malignant potential in breast
      cancer. In this study, expression and subcellular localization of GLUT1 was
      analysed in vivo in breast cancer tissue specimens with differing malignant
      potential, based on the Scarff-Bloom-Richardson (SBRI, II, III) histological
      grading system, and in vitro in the breast cancer cell lines, MDA-MB-468 and MCF
      7, and in MDA-MB-468 cells grown as xenografts in nude athymic BALB/c male mice.
      In situ hybridization analyses demonstrated similar levels of GLUT1 mRNA
      expression in tissue sections from breast cancers of all histological grades.
      However, GLUT1 protein was expressed at higher levels in grade SBRII cancer,
      compared with SBRI and SBRIII, and associated with the expression of the
      proliferation marker PCNA. Immunolocalization analyses in SBRII cancers
      demonstrated a preferential localization of GLUT1 to the portions of the cellular
      membrane that faced neighbouring cells and formed 'canaliculi-like structures',
      that we hypothesize could have a potential role as 'nutritional channels'. A
      similar pattern of GLUT1 localization was observed in confluent cultures of MDA
      MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts, but not in the
      normal breast epithelial cell line HMEC. However, no relationship between GLUT1
      expression and malignant potential of human breast cancer was observed.
      Preferential subcellular localization of GLUT1 could represent a physiological
      adaptation of a subset of breast cancer cells that form infiltrative tumours with
      a nodular growth pattern and that therefore need a major diffusion of glucose
      from blood vessels.

PMID- 19602044
TI  - Statin-induced calcification in human mesenchymal stem cells is cell death
      related.
AB  - Statins are widely used in clinics to lower cholesterol levels. Recently, they
      have been shown to positively affect bone formation and bone mass in a rat model.
      The aim of this study was to investigate the effect of pravastatin, simvastatin
      and lovastatin on the osteoblastic differentiation of human mesenchymal stem
      cells (MSCs) in vitro. Cell number, alkaline phosphatase (ALP) activity, matrix
      mineralization and gene expression pattern were determined. Pravastatin did not
      affect cell differentiation. Simvastatin and lovastatin enhanced bone
      morphogenetic protein 2 (BMP-2) mRNA levels. In contrast, ALP activity and mRNA
      levels were suppressed by statins, as well as the DNA content and cell activity
      (MTT). An increase in apoptotic events was observed at high concentrations of
      statins, along with high Ca-45 incorporation. Lower concentrations of statins did
      not increase apoptotic staining, but also failed to induce calcification. When
      statin-induced calcification did occur, the morphology of the deposits was very
      different from the conventional nodule formation; the calcium was laid down along
      the membranes of the rounded cells suggesting it was as a result of cell death.
      Our results indicate that statins are not able to differentiate human MSCs into
      osteoblasts and that high concentrations of statins (>1 microM) have a cytotoxic
      effect.

PMID- 19602047
TI  - Transcriptional regulation of survivin by c-Myc  in BCR/ABL-transformed cells: 
      implications in anti-leukaemic strategy.
AB  - BCR/ABL can cause chronic myelogenous leukaemia (CML) in part by altering the
      transcription of specific genes with growth- and/or survival-promoting functions.
      Recently, BCR/ABL has been shown to activate survivin, an important regulator of
      cell growth and survival, but the precise molecular mechanisms behind its
      expression and consequences thereof in CML cells remain unclear. Here, we
      reported that BCR/ABL promotes survivin expression and its cytoplasmic
      accumulation. The increase of survivin was largely controlled at the
      transcriptional level through a mechanism mediated by JAK2/PI3K signal pathways
      that activated c-Myc, leading to transactivation of survivin promoter. Dynamic
      down-regulation of survivin was a key event involved in imatinib-induced cell
      death while forced expression of survivin partially counteracted imatinib's
      effect on cell survival. Additionally, shRNA-mediated silencing of survivin or c
      Myc eradicated colony formation of K562 cells in semi-solid culture system,
      implying an essential role for this transcriptional network in BCR/ABL-mediated
      cell transformation and survival. Finally, interruption of c-Myc activity by
      10058-F4 exerted an anti-leukaemia effect with a synergistic interaction with
      imatinib and overcame the anti-apoptosis rescued by IL-3 supplement. In
      conclusion, we have identified JAK2/PI3K-mediated and c-Myc-dependent
      transactivation of survivin as a novel pathway in the transcriptional network
      orchestrated by BCR/ABL. These results suggest that the interference with this
      circuitry might be a potential utility for CML treatment.

PMID- 19602045
TI  - Advanced glycation endproduct (AGE) accumulation  and AGE receptor (RAGE) up
      regulation contribute  to the onset of diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy is manifested by compromised systolic and diastolic
      function. This study was designed to examine the role of advanced glycation
      endproduct (AGE) and AGE receptor (RAGE) in diabetic cardiomyopathy. Heart
      function was assessed in isolated control and streptozotocin-induced diabetic
      hearts following in vivo RAGE gene knockdown using RNA interference.
      Cardiomyocyte mechanical properties were evaluated including peak shortening
      (PS), time-to-PS (TPS) and time-to-90% relengthening (TR(90)). RAGE was assayed
      by RT-PCR and immunoblot. Diabetes significantly enhanced cardiac MG, AGE and
      RAGE levels accompanied with colocalization of AGE and RAGE in cardiomyocytes.
      Diabetes-elicited increase in RAGE was inhibited by in vivo siRNA interference.
      The AGE formation inhibitor benfotiamine significantly attenuated diabetes
      induced elevation in MG, AGE, RAGE and collagen cross-linking without affecting
      hypertriglyceridaemia and hypercholesterolaemia in diabetes. Diabetes markedly
      decreased LV contractility, as evidenced by reduced +/-dP/dt and LV developed
      pressure (LVDP), which were protected by RAGE gene knockdown. In addition, MG
      derived AGE (MG-AGE) up-regulated cardiac RAGE mRNA and triggered cardiomyocyte
      contractile dysfunction reminiscent of diabetic cardiomyopathy. The MG-AGE
      elicited prolongation of TPS and TR(90) was ablated by an anti-RAGE antibody in
      cardiomyocytes. Interestingly, MG-AGE-induced cardiomyocyte dysfunction was
      associated with mitochondrial membrane potential (MMP) depolarization and reduced
      GSK-3beta inactivation in control cardiomyocytes, similar to those from in vivo
      diabetes. Treatment with siRNA-RAGE ablated diabetes-induced MMP depolarization
      and GSK-3beta inactivation. Collectively, our result implicated a role of AGE
      RAGE in the pathogenesis of diabetic cardiomyopathy.

PMID- 19602048
TI  - Ginkgolide B preconditioning protects neurons against ischaemia-induced
      apoptosis.
AB  - Ischaemic preconditioning (IP) has been reported to protect the brain against
      subsequent lethal ischaemia, but it has not been used clinically to prevent
      ischaemic injury because of safety concerns. The aim of the present study was to
      see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect
      neurons against ischaemic injury; if so, which mechanism is involved. Cultured
      mouse cortical neurons at day 8 were pre-treated with GB (120 micromol/l) for 24
      hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to
      induce IP before being treated with severe ischaemia (5 hrs). GB and IP
      significantly increased cell viability, expression of hypoxia-inducible factor-1
      alpha (HIF-1alpha), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p
      Bad) and phosphorylated glycogen synthase kinase- 3beta at serine 9 (p-GSK
      3beta), and decreased the percentage of apoptotic cells and the level of active
      caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific
      inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the
      enhanced expression of HIF-1alpha, EPO and 136p-Bad induced by GB and IP. These
      results suggest that GB, like IP in neurons, is capable of preconditioning
      against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K
      signalling pathway.

PMID- 19602049
TI  - Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival
      during resuscitation.
AB  - Severe haemorrhage is a common cause of death despite the recent advances in
      critical care. Conventional resuscitation fluids are designed to re-establish
      tissue perfusion, but they fail to prevent inflammatory responses during
      resuscitation. Our previous studies indicated that the vagus nerve can modulate
      systemic inflammation via the alpha7 nicotinic acetylcholine receptor
      (alpha7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains
      systemic inflammation and improves survival during resuscitation. Resuscitation
      with GTS rescued all the animals from lethal haemorrhage in a concentration
      dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the
      production of characteristic inflammatory and cardiodepressant factors including
      tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1).
      Resuscitation with GTS was particularly effective in restraining systemic TNF
      responses and inhibiting its production in the spleen. At the molecular level,
      GTS inhibited p65RelA but not RelB NF-kappaB during resuscitation. Unlike non
      specific nicotinic agonists, GTS inhibited serum protein TNF levels in both
      normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited
      poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that
      GTS provides significant advantages as compared with non-specific nicotinic
      agonists, and it could be a promising anti-inflammatory supplement to improve
      survival during resuscitation.

PMID- 19602050
TI  - Quantitative proteomic analysis of the cerebrospinal fluid of patients with
      multiple sclerosis.
AB  - The diagnosis of multiple sclerosis (MS) is challenging for the lack of a
      specific diagnostic test. Recent researches in quantitative proteomics, however,
      offer new opportunities for biomarker discovery and the study of disease
      pathogenesis. To find more potential protein biomarkers, we used two
      technologies, 2-dimensional fluorescence difference in-gel electrophoresis (2D
      DIGE), followed by matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) and ultra-performance liquid chromato-graph
      coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS), to
      quantitatively analyse differential proteomic expression in the cerebrospinal
      fluid (CSF) between patients with MS (the experiment group) and patients with
      other neurological diseases (ONDs; the control group). Analysis by the former
      technology identified more than 43 different protein spots (39 proteins), of
      which 17 spots (13 proteins) showed more than 1.5-fold difference in abundance as
      analysed by DeCyder software (GE Healthcare, Piscataway. NJ, USA) between the MS
      and the ONDs groups. The expression of five protein spots was elevated and the
      expression of 12 protein spots was decreased in the MS group. Meanwhile, the
      latter method, UPLC/Q-TOF MS showed 68 different proteins. There were 45 proteins
      with a difference of more than 1.5 folds between the two groups, in which the
      expression of 20 proteins was elevated and the expression of 25 proteins was
      decreased in the MS group. Data provided by the two methods indicated that the
      proteins overlapped ratio was 27% in the 26 significant proteins that had the
      same regulation tendency. The differential CSF proteins were analysed further by
      biological network and it revealed interaction of them. The subsequent ELISA
      measuring the concentration of cystatin C (P < 0.01), which was one of the
      proteins discovered simultaneously with the two technologies, confirmed the
      results of the two quantitative proteomic analysis. The combination of the two
      quantitative proteomic technologies was helpful in discovering differentially
      expressed proteins that may have a connection with MS disease physiology and
      serve as useful biomarkers for diagnosis and treatment of MS diseases.

PMID- 19602052
TI  - Explant-derived human dental pulp stem cells enhance differentiation and
      proliferation potentials.
AB  - Numerous stem cell niches are present in the different tissues and organs of the
      adult human body. Among these tissues, dental pulp, entrapped within the 'sealed
      niche' of the pulp chamber, is an extremely rich site for collecting stem cells.
      In this study, we demonstrate that the isolation of human dental pulp stem cells
      by the explants culture method (hD-DPSCs) allows the recovery of a population of
      dental mesenchymal stem cells that exhibit an elevated proliferation potential.
      Moreover, we highlight that hD-DPSCs are not only capable of differentiating into
      osteoblasts and chondrocytes but are also able to switch their genetic programme
      when co-cultured with murine myoblasts. High levels of MyoD expression were
      detected, indicating that muscle-specific genes in dental pulp cells can be
      turned on through myogenic fusion, confirming thus their multipotency. A
      perivascular niche may be the potential source of hD-DPSCs, as suggested by the
      consistent Ca(2+) release from these cells in response to endothelin-1 (ET-1)
      treatment, which is also able to significantly increase cell proliferation.
      Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in
      DPSCs, probably due to the isolation method that promotes release of
      stem/progenitor cells from perivascular structures. The ability to isolate,
      expand and direct the differentiation of hD-DPSCs into several lineages, mainly
      towards myogenesis, offers an opportunity for the study of events associated with
      cell commitment and differentiation. Therefore, hD-DPSCs display enhanced
      differentiation abilities when compared to DPSCs, and this might be of relevance
      for their use in therapy.

PMID- 19602053
TI  - Transtactin: a universal transmembrane delivery system for Strep-tag II-fused
      cargos.
AB  - The delivery of molecules into cells poses a critical problem that has to be
      solved for the development of diagnostic tools and therapeutic agents acting on
      intracellular targets. Cargos which by themselves cannot penetrate cellular
      membranes due to their biophysical properties can achieve cell membrane
      permeability by fusion to protein transduction domains (PTDs). Here, we
      engineered a universal delivery system based on PTD-fused Strep-Tactin, which we
      named Transtactin. Biochemical characterization of Transtactin variants bearing
      different PTDs indicated high thermal stabilities and robust secondary
      structures. Internalization studies demonstrated that Transtactins facilitated
      simple and safe transport of Strep-tag II-linked small molecules, peptides and
      multicomponent complexes, or biotinylated proteins into cultured human cells.
      Transtactin-introduced cargos were functionally active, as shown for horseradish
      peroxidase serving as a model protein. Our results demonstrate that Transtactin
      provides a universal and efficient delivery system for Strep-tag II-fused cargos.

PMID- 19602051
TI  - PKR, the double stranded RNA-dependent protein kinase as a critical target in
      Alzheimer's disease.
AB  - Amyloid beta-peptide (Abeta) deposits and neurofibrillary tangles are key
      hallmarks in Alzheimer's disease (AD). Abeta stimulates many signal transducers
      involved in the neuronal death. However, many mechanisms remain to be elucidated
      because no definitive therapy of AD exists. Some studies have focused on the
      control of translation which involves eIF2 and eIF4E, main eukaryotic factors of
      initiation. The availability of these factors depends on the activation of the
      double-stranded RNA-dependent protein kinase (PKR) and the mammalian target of
      rapamycin (mTOR), respectively. mTOR positively regulates the translation while
      PKR results in a protein synthesis shutdown. Many studies demonstrated that the
      PKR signalling pathway is up-regulated in cellular and animal models of AD and in
      the brain of AD patients. Interestingly, our results showed that phosphorylated
      PKR and eIF2alpha levels were significantly increased in lymphocytes of AD
      patients. These modifications were significantly correlated with cognitive and
      memory test scores performed in AD patients. On the contrary, the mTOR signalling
      pathway is down-regulated in cellular and animal models of AD. Recently, we
      showed that p53, regulated protein in development and DNA damage response 1 and
      tuberous sclerosis complex 2 could represent molecular links between PKR and mTOR
      signalling pathways. PKR could be an early biomarker of the neuronal death and a
      critical target for a therapeutic programme in AD.

PMID- 19602055
TI  - Cell and molecular mechanisms of insulin-induced angiogenesis.
AB  - Angiogenesis, the development of new blood vessel from pre-existing vessels, is a
      key process in the formation of the granulation tissue during wound healing. The
      appropriate development of new blood vessels, along with their subsequent
      maturation and differentiation, establishes the foundation for functional wound
      neovasculature. We performed studies in vivo and used a variety of cellular and
      molecular approaches in vitro to show that insulin stimulates angiogenesis and to
      elucidate the signalling mechanisms by which this protein stimulates microvessel
      development. Mice skin injected with insulin shows longer vessels with more
      branches, along with increased numbers of associated alpha-smooth muscle actin
      expressing cells, suggesting the appropriate differentiation and maturation of
      the new vessels. We also found that insulin stimulates human microvascular
      endothelial cell migration and tube formation, and that these effects occur
      independently of VEGF/VEGFR signalling, but are dependent upon the insulin
      receptor itself. Downstream signalling pathways involve PI3K, Akt, sterol
      regulatory element-binding protein 1 (SREBP-1) and Rac1; inhibition of these
      pathways results in elimination of endothelial cell migration and tube formation
      and significantly decreases the development of microvessels. Our findings
      strongly suggest that insulin is a good candidate for the treatment of ischaemic
      wounds and other conditions in which blood vessel development is impaired.

PMID- 19602057
TI  - Role of EG-VEGF in human placentation: Physiological  and pathological
      implications.
AB  - Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is
      thought to be caused by shallow invasion of the maternal decidua by extravillous
      trophoblasts (EVT). Data suggest that a fine balance between the expressions of
      pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we
      showed that the expression of the new growth factor endocrine gland-derived
      vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls
      after 11 weeks, suggesting an essential role for this factor in early pregnancy.
      Using human villous explants and HTR-8/SVneo, a first trimester extravillous
      trophoblast cell line, we showed differential expression of EG-VEGF receptors,
      PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT
      migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on
      invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP
      9 production. Interference with PKR2 expression, using specific siRNAs, reversed
      the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF
      circulating levels in normal and PE patients. Our results showed that EG-VEGF
      levels were highest during the first trimester of pregnancy and decreased
      thereafter to non-pregnant levels. More important, EG-VEGF levels were
      significantly elevated in PE patients compared with age-matched controls. These
      findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion.
      We speculate that a failure to correctly down-regulate placental expression of EG
      VEGF at the end of the first trimester of pregnancy might lead to PE.

PMID- 19602056
TI  - Mutations in p53, p53 protein overexpression and breast cancer survival.
AB  - p53 is an important tumour suppressor gene that encodes p53 protein, a molecule
      involved in cell cycle regulation and has been inconsistently linked to breast
      cancer survival. Using archived tumour tissue from a population-based sample of
      859 women diagnosed with breast cancer between 1996 and 1997, we determined p53
      mutations in exons 5-8 and p53 protein overexpression. We examined the
      association of p53 mutations with overexpression and selected tumour clinical
      parameters. We assessed whether either p53 marker was associated with survival
      through 2002, adjusting for other tumour markers and prognostic factors. The
      prevalence of protein overexpression in the tumour was 36% (307/859) and of any
      p53 mutation was 15% (128/859). p53 overexpression was positively associated with
      the presence of any p53 mutation (odds ratio [OR]= 2.2, 95% confidence interval
      [CI]= 1.5-3.2), particularly missense mutations (ER = 7.0, 95% CI = 3.6-13.7).
      Negative oestrogen and progesterone receptor (ER/PR) status was positively
      associated with both p53 protein overexpression (= 2.6, 95% CI = 1.7-4.0) and p53
      mutation (OR = 3.9, 95% CI = 2.4-6.5). Any p53 mutation and missense mutations,
      but not p53 protein overexpression, were associated with breast cancer-specific
      mortality (hazard ratio [HR]= 1.7, 95% CI = 1.0-2.8; HR = 2.0, 95% CI = 1.1-3.6,
      respectively) and all-cause mortality (HR = 1.5, 95% CI = 1.0-2.4; HR = 2.0, 95%
      CI = 1.2-3.4, respectively); nonsense mutations were associated only with breast
      cancer-specific mortality (HR = 3.0, 95% CI = 1.1-8.1). These associations
      however did not remain after adjusting for ER/PR status. Thus, in this population
      based cohort of women with breast cancer, although p53 protein overexpression and
      p53 mutations were associated with each other, neither independently impacted
      breast cancer-specific or all-causing mortality, after considering ER/PR status.

PMID- 19602059
TI  - Molluscum contagiosum involving an epidermoid cyst with xanthogranuloma-like
      reaction in an HIV-infected patient.
AB  - BACKGROUND: Molluscum contagiosum (MC) causes characteristic cutaneous lesions
      that occur mainly in children, sexually active adults, and immunocompromised
      individuals, especially those with human immunodeficiency virus (HIV) infection.
      Patients infected with HIV, particularly those with advanced disease, have an
      increased incidence, up to 33.3%, of MC in non-anogenital areas. MC has been
      rarely found to be associated with epidermoid cysts. CASE REPORT: A 44-year-old
      male with HIV infection presented with the complaint of a-3-month history of a
      tender nodule on the left neck. H&E stained sections showed a ruptured cyst,
      lined with squamous epithelium showing cytopathic changes of MC, and a
      xanthogranuloma-like inflammatory reaction with characteristic Touton-type giant
      cells. CONCLUSION: MC infections are common, however MC associated with
      epidermoid cysts is infrequent. A few cases of MC occurring in epidermoid cysts
      have previously been reported. We are presenting a case of MC involving an
      epidermoid cyst in an AIDS patient, with a unique xanthogranuloma-like reaction.
      Xanthogranulomatous (XG) reactions have been infrequently reported in association
      with other viral infections, however, poxvirus-associated XG reaction has only
      been observed in animals. This is the first reported case of MC-associated XG
      reaction in humans.

PMID- 19602060
TI  - White sponge nevus presenting as genital lesions in a 28-year-old female.
AB  - A case is presented of white plaques occurring predominantly on the vulvar mucosa
      of a 28-year-old female diagnosed as white sponge nevus (WSN). WSN is a rare,
      autosomal dominant disorder involving mucous membranes. It predominantly affects
      the oral mucosa; however, it has been reported to rarely involve extraoral
      mucosal sites. In this case, histology and family history were key features
      leading to the correct diagnosis. WSN is an extremely rare cause of vulvar
      leukoplakia, yet it is important to recognize to allow for appropriate genetic
      counseling of this autosomal dominant disorder and to avoid misdiagnosis and the
      potential for subsequent exposure to ineffective treatment modalities.

PMID- 19602061
TI  - Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis.
AB  - The author reports a very rare case of cutaneous metastasis of sarcomatoid
      carcinoma of the lung. The skin metastasis was an initial presentation. A 67-year
      old man consulted our hospital because of left chest skin mass. An excisional
      biopsy was performed, and it showed proliferation of malignant sarcomatoid
      spindle and polygonal cells in the deep dermis and subcutis remote from the
      epidermis and appendages. Immunohistochemically, the tumor cells were positive
      for pancytokeratins, cytokeratin (CK) 7, CK 18, vimentin, p53, Ki-67 (95%) and
      PDGFRA. They were negative for high molecular weight CK, CK 5/6, CK 14, CK 19, CK
      20, epithelial membrane antigen, TTF-1, CEA, desmin, S100 protein, alpha-smooth
      muscle actin, p63, CD34, surfactant apoprotein A, chromogranin, synaptophysin,
      neuron-specific enolase, CD68, CD56, D2-40, calretinin and KIT. A pathological
      diagnosis of metastatic sarcomatoid carcinoma probably originating from the lung
      was made. Then, the patient was admitted to our hospital, and imaging modalities
      including computed tomography (CT) and magnetic resonance imaging (MRI) revealed
      a tumor in the left lung. No other tumors were detected in the imaging
      techniques. Lung biopsy was planned, but the patient suddenly died; the cause of
      death was unclear. Autopsy was not performed. The present report suggests that
      sarcomatoid carcinoma of the lung should be considered in cutaneous metastatic
      lesions.

PMID- 19602054
TI  - Oxidative stress induced lung cancer and COPD: opportunities for epigenetic
      therapy.
AB  - Reactive oxygen species (ROS) form as a natural by-product of the normal
      metabolism of oxygen and play important roles within the cell. Under normal
      circumstances the cell is able to maintain an adequate homeostasis between the
      formation of ROS and its removal through particular enzymatic pathways or via
      antioxidants. If however, this balance is disturbed a situation called oxidative
      stress occurs. Critically, oxidative stress plays important roles in the
      pathogenesis of many diseases, including cancer. Epigenetics is a process where
      gene expression is regulated by heritable mechanisms that do not cause any direct
      changes to the DNA sequence itself, and disruption of epigenetic mechanisms has
      important implications in disease. Evidence is emerging that histone deacetylases
      (HDACs) play decisive roles in regulating important cellular oxidative stress
      pathways including those involved with sensing oxidative stress and those
      involved with regulating the cellular response to oxidative stress. In particular
      aberrant regulation of these pathways by HDACs may play critical roles in cancer
      progression. In this review we discuss the current evidence linking epigenetics
      and oxidative stress and cancer, using chronic obstructive pulmonary disease and
      non-small cell lung cancer to illustrate the importance of epigenetics on these
      pathways within these disease settings.

PMID- 19602062
TI  - Co-existing basal cell carcinoma and blue nevus in an African-American woman.
AB  - A 67-year-old African-American woman presented with an enlarging darkly pigmented
      plaque on her scalp. Histopathologic examination revealed a basal cell carcinoma
      juxtaposed to a blue nevus. Interestingly, the most common types of cutaneous
      collision tumors include melanocytic nevus and basal cell carcinoma. Whether
      these combinations are simply because of chance or may have a pathophysiologic
      mechanism is contentious. This is the first documented case of a basal cell
      carcinoma co-existing alone with a blue nevus.

PMID- 19602063
TI  - Superficial morphea: 20-year follow up in a patient with concomitant psoriasis
      vulgaris.
AB  - Superficial morphea, a newly described variant of morphea, manifests clinically
      with hypopigmented or hyperpigmented patches that lack induration. The lesions
      show on biopsy dermal sclerosis in the superficial to mid-reticular dermis. So
      far, all cases reported in the literature were skin limited. In this report, we
      describe a 24-year-old female patient who developed at the age of 4 years plaques
      characteristic, both clinically and histologically, of superficial morphea. The
      patient developed later on psoriasis vulgaris. Although the association of
      scleroderma and psoriasis is rarely reported in the literature, most reports
      describe a progressive systemic course of scleroderma whenever the two diseases
      co-exist. This is the first report to describe superficial morphea in association
      with psoriasis and to provide a 20-year follow-up period during which the
      superficial morphea remained relatively stable with no evidence of systemic
      involvement.

PMID- 19602065
TI  - Symplastic glomus tumor - a rare but distinct benign histological variant with
      analogy to other 'ancient' benign skin neoplasms.
AB  - A 78-year-old woman presented with a nail deformity of the index finger of the
      left hand associated with paroxysmal pain upon cold exposure. Histologically, a
      well-circumscribed tumor of 3 mm diameter was found in the dermis. The neoplastic
      cells in some areas were of pronouncedly variable size and cytomorphology, mostly
      epithelioid in shape, with eosinophilic cytoplasm and indistinctly defined cell
      borders. Pronounced nuclear pleomorphism and atypia were striking features, but
      no mitotic figures were noted. Multinuclear cells were present as were numerous
      small-to-medium vessels throughout the tumor. The tumor stroma showed myxoid
      areas. Immunohistochemistry showed cytoplasmic and membranous expression of
      smooth muscle actin and vimentin. The histological features and immunoprofile
      were consistent with the diagnosis of symplastic glomus tumor, a rare
      histological variant, which has been defined as a glomus tumor exhibiting marked
      nuclear atypia, in the absence of any other criteria for malignancy. The
      biological behavior of the tumor is benign. It is essential to differentiate this
      entity from malignant glomus tumor, which has metastatic potential. Even
      prominent cellular atypia and nuclear pleomorphism in a glomus tumor as in our
      case is not a marker of malignancy in the absence of additional criteria.

PMID- 19602064
TI  - A finding of granuloma faciale associated with basal cell carcinoma.
AB  - The clinical differential diagnosis of violaceous plaques on the face is broad
      and includes both neoplasms and inflammatory dermatoses. We report the first case
      of a basal cell carcinoma (BCC) superficial to an underlying granuloma faciale
      (GF). This is a single case report with clinicopathological correlation.
      Histological examination of a skin biopsy from the cheek revealed superficial BCC
      and GF. This case constitutes the first reported finding of coincident GF and
      BCC.

PMID- 19602066
TI  - D2-40 highlights lymphatic vessel proliferation of angiolymphoid hyperplasia with
      eosinophilia.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign, uncommon
      idiopathic condition, characterized by cutaneous papules or nodules, whose
      etiopathogenesis is still unclear. It has been considered an angioproliferating
      lesion (epithelioid hemangioma) since histologically it is marked by a
      proliferation of blood vessels, accompanied by an inflammatory infiltrate,
      consisting mainly of lymphocytes and eosinophils. We present a case of ALHE
      assessed immunohistochemically for D2-40-a new marker for lymphatic endothelial
      cells. A biopsy specimen obtained from the same anatomical area of a healthy
      individual served as a normal control. The ALHE specimen showed increased number
      of lymphatic vessels when stained for D2-40, whereas the endothelial cells lining
      blood vessels were negative. The specificity of D2-40 for lymphatic vessels was
      further substantiated by studying Factor VIII-related antigen expression in
      consecutive sections of both ALHE and the control specimen. A reverse pattern was
      appreciated-blood vessels showed Factor VIII positive labeling, whereas lymphatic
      endothelial cells remained unlabeled. We therefore assume that apart from the
      lymphocytic infiltrate in the lesion, the recognized lymphoid component in ALHE
      is due to lymphatic vessel proliferation as well. Hence, this condition may be
      considered as possibly derived from lymphatic endothelium.

PMID- 19602067
TI  - PRP with subcorneal acantholysis: case report and review.
AB  - Although the clinical findings of pityriasis rubra pilaris (PRP) are striking,
      the microscopic diagnosis can be difficult because changes can be subtle and can
      overlap with other skin diseases. Suprabasal acantholysis can be seen in PRP,
      mimicking pemphigus vulgaris. We report a patient with PRP whose initial biopsies
      demonstrated subcorneal acantholysis mimicking pemiphigus foliaceus.

PMID- 19602068
TI  - Indolent CD8+ lymphoid proliferation of the ear: a phenotypic variant of the
      small-medium pleomorphic cutaneous T-cell lymphoma?
AB  - BACKGROUND: Recently, Petrella et al. described four patients with an unusual
      CD8+ lymphoid proliferation arising on the ear. These cases do not correspond
      clearly to any recognized category of cutaneous T-cell lymphoma (CTCL) described
      in the World Health Organization (WHO)/European Organization for Research and
      Treatment of Cancer (EORTC) 2005 classification. METHODS AND RESULTS: Three
      patients (all men; median age 64; range: 61-69) presented with plaques or small
      tumors localized on the ears. All lesions showed histopathologically a dense,
      diffuse infiltration of lymphocytes within the entire dermis without
      epidermotropism. Cytomorphology revealed predominance of medium-sized pleomorphic
      lymphocytes. Immunohistochemistry showed a cytotoxic phenotype (CD3 + /CD4 -/CD8
      +). Polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR)-gamma
      gene revealed a monoclonal rearrangement in two of three patients. Follow-up data
      of two patients were available; one is alive without skin or systemic
      manifestations of the disease after 28 months, whereas the other is alive with
      persistent skin disease after 7 months. CONCLUSIONS: Our observation confirms
      that some patients present with a peculiar lymphoid proliferation of small-medium
      pleomorphic cytotoxic lymphocytes located on the ear, probably representing a
      phenotypic variant of the cutaneous small/medium pleomorphic T-cell lymphoma
      (CSMPTCL). These cases should not be misinterpreted as a high-grade cytotoxic
      lymphoma.

PMID- 19602069
TI  - Acantholytic tumor of the nail: acantholytic dyskeratotic acanthoma.
AB  - Acantholytic dyskeratotic acanthomas of the skin have been recently described in
      several publications. They differ from acantholytic acanthomas by the presence of
      dyskeratosis. However these tumors have never been described in nails. We report
      three cases localized on the thumb nail.

PMID- 19602070
TI  - Histiocyte-rich pleomorphic mastocytoma: an uncommon variant mimicking juvenile
      xanthogranuloma and Langerhans cell histiocytosis.
AB  - An 11-year old Caucasian female with a remote history of urticaria pigmentosa
      presented with a neck mass. A biopsy demonstrated a large intradermal nodule
      composed of unusually large epithelioid mast cells, including a prominent subset
      with bi-lobed and multi-lobed nuclei. By immunohistochemistry, the cells
      expressed CD117 (C-Kit), mast cell tryptase, CD68, and CD25, and were negative
      for CD163, CD1a, and S-100, confirming the diagnosis of mastocytoma. Equally
      prominent was an admixed infiltrate of CD68 and CD163-positive xanthomatous
      histiocytes that included Touton-type giant cells. Eosinophils were abundant. At
      7 months follow-up, there was no recurrence of the lesion following complete
      excision. However, given the unusual cytologic features, close clinical
      observation is warranted, as the long-term biologic potential of mastocytoma with
      this degree of cytologic atypia is uncertain. Awareness of this unusual
      morphologic variant is also important as the histologic features may mimic such
      childhood neoplasms as juvenile xanthogranuloma and Langerhans cell
      histiocytosis.

PMID- 19602071
TI  - Effectiveness of imiquimod limited to dermal melanoma metastases, with
      simultaneous resistance of subcutaneous metastasis.
AB  - Successful management of epithelial skin cancers with imiquimod 5% cream
      (Aldara), an immunomodulatory agent, led to speculation that it may promote an
      immune response against melanoma. Studies, mostly case reports, have assessed the
      value of imiquimod as a topical treatment for dermal melanoma metastases that
      prove difficult to manage surgically. The precise value of imiquimod, however, in
      treatment of dermal and subcutaneous metastases remains unclear. A case at our
      institution elucidates histopathologically that subcutaneous metastases may
      progress despite excellent treatment of superficial dermis in the same location.
      In preparation for a clinical trial using imiquimod to treat patients with dermal
      melanoma metastases, we have treated several patients off protocol. We present a
      case report in which the observed changes are documented photographically and
      histologically. The patient experienced dramatic improvement in the locally
      treated dermis with concurrent regional treatment failure in the subcutaneous
      space. Our experience supports growing evidence that imiquimod for some provides
      an effective option for dermal disease. The unique histological documentation we
      provide regarding the differential effectiveness of imiquimod in treating various
      tissue components may help guide future investigations regarding optimal clinical
      application of imiquimod therapy for melanoma metastases.

PMID- 19602073
TI  - Gadolinium-induced nephrogenic systemic fibrosis is associated with insoluble Gd
      deposits in tissues: in vivo transmetallation confirmed by microanalysis.
AB  - BACKGROUND: Nephrogenic systemic fibrosis (NSF) is an extremely debilitating
      systemic fibrosing disorder affecting renal failure patients. The association of
      NSF with gadolinium (Gd) containing magnetic resonance contrast agents was noted
      in 2006. Gd deposition in skin biopsies was demonstrated shortly thereafter.
      METHODS: We used automated scanning electron microscopy (SEM)/energy dispersive x
      ray spectroscopy for in situ quantitative analysis of insoluble Gd-containing
      deposits, recording multi-elemental composition and spatial distribution of
      detected features. RESULTS: Gd was detected in all 29 patients (53 of 57 skin
      biopsies) with NSF, biopsied from 2 weeks to 3 years after Gd exposure. Gd
      concentration ranged from 1 to 2270 cps/mm(2) and was detected predominantly in
      the deep dermis and subcutaneous fibrous septa. Gd was found associated with Ca,
      P and sometimes Fe or Zn. Patients with sequential biopsies showed persistence or
      increase of Gd in tissues (6 of 11). Transmission electron microscopy (TEM)
      identified the intracellular deposits in fibrocytes and macrophages. CONCLUSIONS:
      The demonstration of insoluble tissue deposits of Gd with co-associated elements
      clearly confirms in vivo transmetallation and dissociation of soluble Gd
      chelates. Toxic Gd(3+) may trigger fibrosis under permissive conditions, e.g., in
      renal insufficiency. Pathologists and clinicians need to be aware of this serious
      but preventable disease.

PMID- 19602072
TI  - Diagnosis of mycosis fungoides with different algorithmic approaches.
AB  - BACKGROUND: Algorithmic scoring approaches for evaluating early cases of mycosis
      fungoides (MF) provide a degree of diagnostic standardization. At the UWMC,
      biopsies from clinically concerning cases for MF are individually reviewed by a
      panel of pathologists and an average score is assigned to each biopsy reflecting
      the degree of suspicion for a diagnosis of MF; however, such an approach may not
      be practical outside of an academic center. METHODS: 78 cases characterized in
      our institution, with the diagnosis confirmed by clinicopathologic
      correlation/clinical follow-up were evaluated with two different algorithms,
      based entirely on histologic evaluation (Guitart algorithm) and partial
      implementation of the ISCL algorithm evaluating histology, immunohistochemistry
      and T-cell clonality. RESULTS: A receiver operating characteristic curve
      comparing the results of the two approaches in early MF cases showed no
      statistical difference between the areas under the two curves. Increased stages
      of MF showed variable loss of T-cell antigens by immunohistochemistry and higher
      rates of detectable clonality. CONCLUSION: We could not document a statistically
      significant advantage of adding ancillary immunohistochemical and molecular
      testing to careful histologic evaluation in the workup of suspected cases of
      early MF. A systemic approach to histologic diagnosis by a single pathologist
      correlated favorably to the MF panel diagnosis.

PMID- 19602074
TI  - The histopathological characteristics of livedo reticularis.
AB  - BACKGROUND: Livedo reticularis (LR) is a skin disorder characterized by a reddish
      blue mottling of the skin in a "fishnet" reticular pattern. The aim of this study
      was to investigate the major histopathological characteristics of LR and
      determine whether the histopathology of LR is more common in whitish areas or in
      the erythematous areas. METHODS: A clinical survey was carried out that included
      16 patients with LR. The histopathological features were investigated with
      immunostains for factor VIII-related antigen, as well as routine hematoxylin
      eosin. RESULTS: There were no significant differences in thrombi, arterial
      obliteration, or RBC aggregates between the central blanched area and the
      peripheral erythematous areas. The computer-assisted image analyses of factor
      VIII-related antigen-stained sections revealed no significant difference in the
      number of dermal blood vessels and telangiectasia between the areas studied.
      There were nine cases that showed one or more of the histopathological features
      of LR in either the central blanched areas or the peripheral erythematous areas.
      CONCLUSION: Our findings suggest that multiple punch biopsies should be performed
      in patients suspected of LR including both the peripheral erythematous and
      central whitish areas to increase the diagnostic yield.

PMID- 19602075
TI  - Is plexiform fibro-histiocytic tumor a deep form of cellular neurothekeoma?

PMID- 19602076
TI  - Morphology, phylogeny, and diversity of Trichonympha (Parabasalia:
      Hypermastigida) of the wood-feeding cockroach Cryptocercus punctulatus.
AB  - Trichonympha is one of the most complex and visually striking of the
      hypermastigote parabasalids-a group of anaerobic flagellates found exclusively in
      hindguts of lower termites and the wood-feeding cockroach Cryptocercus-but it is
      one of only two genera common to both groups of insects. We investigated
      Trichonympha of Cryptocercus using light and electron microscopy (scanning and
      transmission), as well as molecular phylogeny, to gain a better understanding of
      its morphology, diversity, and evolution. Microscopy reveals numerous new
      features, such as previously undetected bacterial surface symbionts, adhesion of
      post-rostral flagella, and a distinctive frilled operculum. We also sequenced
      small subunit rRNA gene from manually isolated species, and carried out an
      environmental polymerase chain reaction (PCR) survey of Trichonympha diversity,
      all of which strongly supports monophyly of Trichonympha from Cryptocercus to the
      exclusion of those sampled from termites. Bayesian and distance methods support a
      relationship between Trichonympha species from termites and Cryptocercus,
      although likelihood analysis allies the latter with Eucomonymphidae. A
      monophyletic Trichonympha is of great interest because recent evidence supports a
      sister relationship between Cryptocercus and termites, suggesting Trichonympha
      predates the Cryptocercus-termite divergence. The monophyly of symbiotic bacteria
      of Trichonympha raises the intriguing possibility of three-way co-speciation
      among bacteria, Trichonympha, and insect hosts.

PMID- 19602077
TI  - Photosynthetic eukaryotes of freshwater wetland biofilms: adaptations and
      structural characteristics of the extracellular matrix in the green alga,
      Cosmarium reniforme (Zygnematophyceae, Streptophyta).
AB  - Cosmarium reniforme (Zygnematophyceae, Streptophyta) is a green alga that is
      commonly found in biofilms of wetlands of the Adirondack region, NY (USA). Two
      distinctive characteristics that are critical to this alga's survival in a
      benthic biofilm are its elaborate cell morphology and extracellular matrix (ECM).
      In this study, ultrastructural, immunocytochemical, and experimental
      methodologies were employed in order to elucidate the cellular characteristics
      that are critical for survival in a biofilm. The ECM consists of a thick,
      outwardly lobed cell wall (CW), which contains a patterned network of
      structurally complex pores. Each pore consists of a narrow channel, terminating
      internally at a bulb that invaginates localized regions of the plasma membrane.
      The outer region of the pore contains arabinogalactan protein-like and extensin
      epitopes that are likely involved in adhesion mechanisms of the cell. External to
      the CW is the extracellular polymeric substance that is employed in ensheathment
      of the cell to the substrate and in gliding motility. The architectural
      design/biochemical make-up of the CW and a secretory system that encompasses the
      coordinated activities of the endomembrane and cytomotile/cytoskeletal systems
      provide the organism with effective mechanisms to support life within the biofilm
      complex.

PMID- 19602078
TI  - Phylogeny and systematic position of Zosterodasys (Ciliophora, Synhymeniida): a
      combined analysis of ciliate relationships using morphological and molecular
      data.
AB  - The Synhymeniida is characterized both by a band of somatic dikinetids, the
      synhymenium, extending across the surface of the cell and by a ventral cell mouth
      lacking specialized feeding cilia but subtended by a well-developed cyrtos. The
      synhymeniids have been hypothesized to be members of the class Nassophorea but
      our previous ultrastructural study of the synhymeniid genus Zosterodasys did not
      show any clear synapomorphies that would permit definitive placement in the
      Nassophorea or as a sister taxon to any of the other ciliate groups possessing a
      cyrtos. In the present study, simultaneous analysis of morphological and small
      subunit rDNA molecular data indicates that the Synhymeniida are sister to the
      class Phyllopharyngea and that this clade is, in turn, sister to the remaining
      Nassophorea, although this result is sensitive to dataset inclusion and alignment
      parameters. While this suggests that taxa with a ventral cyrtos might be united
      into a named taxon (e.g. resurrecting the Hypostomata), additional data are
      needed to reach a definitive conclusion.

PMID- 19602079
TI  - Small subunit rRNA phylogenies show that the class nassophorea is not
      monophyletic (Phylum Ciliophora).
AB  - The hypostome ciliates have been generally classified into two classes,
      Phyllopharyngea and Nassophorea. The status of Nassophorea and its relationship
      with Phyllopharyngea is one of the most controversial issues in ciliate
      systematics. Here we focus on the phylogenetic interrelationships of Nassophorea
      and Phyllopharyngea based on small subunit ribosomal RNA gene sequences. The
      three nassophorean subgroups, synhymeniids, microthoracids, and nassulids, each
      emerged as monophyletic, with synhymeniids as a sister group of Phyllopharyngea,
      and microthoracids as a sister of the synhymeniids+Phyllopharyngea clade in all
      phylogenies. The exact placement of the nassulids, however, remains uncertain.
      Following a detailed analysis of phenotypic characters, we hypothesize that: (1)
      the Phyllopharyngea could have evolved from synhymeniids, with the further
      development of their subkinetal microtubules as one of the major events; and (2)
      the development of monokinetid structures, as well as the reduction and
      specialization of the cyrtos and cortex, might have occurred during the
      diversifications of the microthoracids, synhymeniids, and Phyllopharyngea from a
      common ancestor. Expanding the class Phyllopharyngea to include the synhymeniids
      as a subclass, and designating a new subclass Subkinetalia n. subcl. for the
      group comprising cyrtophorians, chonotrichians, rhynchodians, and suctorians, are
      proposed.

PMID- 19602080
TI  - The RAB family GTPase Rab1A from Plasmodium falciparum defines a unique paralog
      shared by chromalveolates and rhizaria.
AB  - The RAB GTPases, which are involved in regulation of endomembrane trafficking,
      exhibit a complex but incompletely understood evolutionary history. We elucidated
      the evolution of the RAB1 subfamily ancestrally implicated in the endoplasmic
      reticulum-to-Golgi traffic. We found that RAB1 paralogs have been generated over
      the course of eukaryotic evolution, with some duplications coinciding with the
      advent of major eukaryotic lineages (e.g. Metazoa, haptophytes). We also
      identified a unique, derived RAB1 paralog, orthologous to the Plasmodium Rab1A,
      that occurs in stramenopiles, alveolates, and Rhizaria, represented by the
      chlorarachniophyte Gymnochlora stellata. This finding is consistent with the
      recently documented existence of a major eukaryotic clade ("SAR") comprising
      these three lineages. We further found a Rab1A-like protein in the cryptophyte
      Guillardia theta, but it exhibits unusual features among RAB proteins: absence of
      a C-terminal prenylation motif and an N-terminal extension with two MSP domains;
      and its phylogenetic relationships could not be established convincingly due to
      its divergent nature. Our results nevertheless point to a unique membrane
      trafficking pathway shared by at least some lineages of chromalveolates and
      Rhizaria, an insight that has implications towards interpreting the early
      evolution of eukaryotes and the endomembrane system.

PMID- 19602082
TI  - The distribution of Elongation Factor-1 Alpha (EF-1alpha), Elongation Factor-Like
      (EFL), and a non-canonical genetic code in the ulvophyceae: discrete genetic
      characters support a consistent phylogenetic framework.
AB  - The systematics of the green algal class Ulvophyceae have been difficult to
      resolve with ultrastructural and molecular phylogenetic analyses. Therefore, we
      investigated relationships among ulvophycean orders by determining the
      distribution of two discrete genetic characters previously identified only in the
      order Dasycladales. First, Acetabularia acetabulum uses the core translation
      GTPase Elongation Factor 1alpha (EF-1alpha) while most Chlorophyta instead
      possess the related GTPase Elongation Factor-Like (EFL). Second, the nuclear
      genomes of dasycladaleans A. acetabulum and Batophora oerstedii use a rare non
      canonical genetic code in which the canonical termination codons TAA and TAG
      instead encode glutamine. Representatives of Ulvales and Ulotrichales were found
      to encode EFL, while Caulerpales, Dasycladales, Siphonocladales, and Ignatius
      tetrasporus were found to encode EF-1alpha, in congruence with the two major
      lineages previously proposed for the Ulvophyceae. The EF-1alpha of I. tetrasporus
      supports its relationship with Caulerpales/Dasycladales/Siphonocladales, in
      agreement with ultrastructural evidence, but contrary to certain small subunit
      rRNA analyses that place it with Ulvales/Ulotrichales. The same non-canonical
      genetic code previously described in A. acetabulum was observed in EF-1alpha
      sequences from Parvocaulis pusillus (Dasycladales), Chaetomorpha coliformis, and
      Cladophora cf. crinalis (Siphonocladales), whereas Caulerpales use the universal
      code. This supports a sister relationship between Siphonocladales and
      Dasycladales and further refines our understanding of ulvophycean phylogeny.

PMID- 19602081
TI  - Paravahlkampfia francinae n. sp. masquerading as an agent of primary amoebic
      meningoencephalitis.
AB  - Paravahlkampfia francinae n. sp., a new species of the free-living amoeba genus
      Paravahlkampfia, designated as CDC:V595, was isolated from the cerebrospinal
      fluid of a patient with headache, sore throat, and vomiting, typical symptoms of
      primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri. The
      isolate grew at 33 degrees C, 37 degrees C, 40 degrees C, and 42 degrees C and
      destroyed mammalian cell cultures. However, it did not kill young mice upon
      intranasal inoculation. P. francinae does not produce flagellates and does not
      grow on agar plates coated with Gram-negative bacteria such as Escherichia coli,
      the usual food source of Paravahlkampfia ustiana, the type species of the genus.
      The trophozoite at light microscopy exhibited eruptive locomotion and possessed a
      single vesicular nucleus. Ultrastructurally, the trophozoites had numerous
      mitochondria with discoidal cristae but did not have a Golgi apparatus. The
      trophozoites differentiated into cysts after consuming most of the monolayer. The
      cyst had an inner well-differentiated endocyst and an outer thin, wrinkled, and
      wavy ectocyst with no pores. During excystation trophozoites ruptured the cyst
      wall and emerged from the cysts. A unique feature seen in the cysts was the
      presence of bacterial endosymbionts, both in the endoplasm and within the cyst
      wall. Full-length sequencing analysis of the 18S and 5.8S RNA genes of P.
      francinae showed that they were distinct from those of other Paravahlkampfia
      species. The patient recovered within a few days indicating that some of the
      previously reported cases of PAM that survived may have been due to P. francinae.

PMID- 19602083
TI  - Light microscopic observations, ultrastructure, and molecular phylogeny of
      Hicanonectes teleskopos n. g., n. sp., a deep-branching relative of diplomonads.
AB  - We describe Hicanonectes teleskopos n. g., n. sp., a heterotrophic flagellate
      isolated from low-oxygen marine sediment. Hicanonectes teleskopos has a ventral
      groove and two unequal flagella, and rapidly rotates during swimming. At the
      ultrastructural level H. teleskopos is a "typical excavate": it displays
      flagellar vanes, a split right microtubular root, "I,""B," and "C" fibres, a
      singlet microtubular root, and a possible composite fibre. Small subunit rRNA
      (SSU rRNA) gene phylogenies and an "arched" B fibre demonstrate that H.
      teleskopos belongs to Fornicata (i.e. diplomonads, retortamonads, and relatives).
      It forms a clade with the deep-branching fornicate Carpediemonas, with moderate
      to-strong bootstrap support, although their SSU rRNA gene sequences are quite
      dissimilar. Hicanonectes differs from Carpediemonas in cell shape, swimming
      behaviour, number of basal bodies (i.e. 4 vs. 3), number of flagellar vanes (i.e.
      2 vs. 3), anterior root organization, and by having a cytopharynx. Like
      Carpediemonas and Dysnectes, Hicanonectes has conspicuous mitochondrion-like
      organelles that lack cristae and superficially resemble the hydrogenosomes of
      parabasalids, rather than the mitosomes of their closer relatives the diplomonads
      (e.g. Giardia).

PMID- 19602084
TI  - First record of the peritrich Trichodina diaptomi Basson and Van As, 1991
      (Protozoa: Ciliophora) on a South American calanoid Notodiaptomus deitersi
      (Poppe, 1890) (Crustacea: Copepoda).
AB  - The ciliate Trichodina was recorded on the calanoid Notodiaptomus deitersi in a
      shallow, eutrophic reservoir, located in the centre-west of Brazil. The species
      was confirmed as Trichodina diaptomi, a species widely distributed in Europe,
      Africa, Asia and Australia. It was observed moving freely over the carapace of
      the copepod, and using its adhesive disc. This is the first record for the
      species in the Americas.

PMID- 19602085
TI  - In vitro physiological responses of Fusarium oxysporum f. sp. niveum to
      exogenously applied syringic acid.
AB  - Plant-microbe interactions are often accompanied by allelochemicals, such as
      syringic acid, released from the host plant. To explore the role of phenolic
      acids released from crop host plants in response to pathogen invasion, we
      examined the allelopathic effect of an artificially applied syringic acid on
      Fusarium oxysporum f. sp. niveum. We demonstrated that the growth and the
      conidial germination rate of F. oxysporum f. sp. niveum were stimulated at lower
      concentrations of syringic acid, though inhibited by higher dosage compared with
      control. The yield of fungus mycotoxin was increased from 60.9% to 561.5%. We
      conclude that syringic acid can be considered as a allelochemical inducer,
      stimulating the relative virulence factors of invading pathogens.

PMID- 19602086
TI  - Characterization of genotypes of Enterocytozoon bieneusi in immunosuppressed and
      immunocompetent patient groups.
AB  - A retrospective phylogenetic analysis was performed on isolates of Enterocytozoon
      bieneusi to characterize the genotypes in different patient cohorts. Fifty-seven
      isolates, collected from patients living in Malawi and the Netherlands, were
      classified by age and immune status of the hosts. Sequence analysis of the
      internal transcribed spacer (ITS) region identified 16 genotypes; nine have not
      previously been described. Genotypes K and D were most prevalent among patient
      groups, whereas genotype C was restricted to transplantation patients receiving
      immunosupressives and genotype B showed a predisposition toward patients living
      with HIV/AIDS. Different genotypes showed more dispersion among isolates from
      Malawi compared with those from the Netherlands. A constructed map estimating the
      genealogy of the ITS region reveals a dynamic evolutionary process between the
      genotypes.

PMID- 19602088
TI  - Seasonal abundances of naked amoebae in biofilms on shells of zebra mussels
      (Dreissena polymorpha) with comparative data from rock scrapings.
AB  - In North America, zebra mussels (Dreissena polymorpha) are notoriously known as
      invasive species. The abundance of naked amoebae sampled from the shells of zebra
      mussels was compared with abundances from rock scrapings at approximately monthly
      intervals for 1 year. The sites were 2 km apart along the same shoreline. No
      significant difference in abundance of naked amoebae (F = 1.44; P <or= 0.270) was
      detected for the two sampling sites. The combined data showed a minimum density
      of naked amoebae in winter, followed by peaks in early spring. The percent
      encysted increased from a low of 1% in the summer to 80% in early winter.

PMID- 19602087
TI  - Revisiting the phylogenetic position of Synchroma grande.
AB  - Two new classes Synchromophyceae and Picophagea, belonging to the heterokonts,
      have been proposed recently in separate studies of 18S rRNA phylogenies. Here we
      revise the 18S phylogeny of these classes by including all available sequenced
      species and applying Bayesian and maximum likelihood methods; Synchroma grande
      groups with the photophagotrophic Chlamydomyxa labyrinthuloides with high
      statistical support. This clade is sister to Chrysophyceae, together they share a
      common ancestry. Our results show that the creation of class Synchromophyceae by
      Horn et al. was premature, because they did not include data from the closely
      related C. labyrinthuloides and Picophagus flagellatus species. A revision of
      these classes should include additional species and most likely multigene
      phylogenies.

PMID- 19602089
TI  - In memoriam: Frederick L. Schuster (1934-2009).

PMID- 19602090
TI  - Development and characterization of a monoclonal antibody against Taura syndrome
      virus.
AB  - We produced a panel of monoclonal antibodies (MAbs) from the fusion of Taura
      syndrome virus variants from Belize (TSV-BZ) immunized BALB/cJ mouse spleen cells
      and non-immunoglobulin secreting SP2/0 mouse myeloma cells. One antibody, 2C4,
      showed strong specificity and sensitivity for TSV in dot-blot immunoassay and
      immunohistochemistry (IHC) analysis. The MAb reacted against native TSV-BZ, TSV
      variants from Sinaloa, Mexico (TSV-SI) and TSV variants from Hawaii (TSV-HI) in
      dot-blot immunoassay. By IHC, the antibody identified the virus in a pattern
      similar to the digoxigenin-labelled TSV-cDNA probe for the TSV-BZ, TSV-HI and TSV
      SI variants, but not for the TSV variants from Venezuela (TSV-VE) and the TSV
      variants from Thailand (TSV-TH). MAb 2C4 did not react against other shrimp
      pathogens or with normal shrimp tissue. Western blot analysis showed a strong
      reaction against CP2, a region of high antigenic variability amongst TSV
      variants. This antibody has potential diagnostic application in detection and
      differentiation of certain TSV biotypes.

PMID- 19602092
TI  - Melanomacrophages in three species of free-ranging sharks from the northwestern
      Atlantic, the blue shark Prionacae glauca (L.), the shortfin mako, Isurus
      oxyrhinchus Rafinesque, and the thresher, Alopias vulpinus (Bonnaterre).
AB  - The melanomacrophage aggregates or cells (MMC) are commonly used as biomarkers of
      exposure to pollution in fish, albeit their numbers and morphological
      characteristics can be influenced not only by environmental toxins but also by a
      range of physiological parameters and pathological conditions. Accordingly,
      before we can use MMC as biomarkers in any fish species, their normal,
      'background' characteristics have to be established in apparently healthy fish.
      The knowledge of MMC in sharks is minimal. The aim of this study was to
      characterize MMC from 51 free-ranging, large pelagic sharks from the northwestern
      Atlantic, including shortfin mako, Isurus oxyrhinchus, thresher, Alopias vulpinus
      and blue shark, Prionacae glauca. The rationale of this study was twofold. First,
      because, sharks have life histories predisposing them to the accumulation of
      environmental toxins they constitute good sentinel species of the health of the
      global marine ecosystem. Second, because many shark populations are in decline or
      threatened by extinction, we need to expand our understanding of their health
      status in order to develop appropriate protective measures. All sharks were
      collected by sports fishing gear between June and August in 2007. Their health
      condition was assessed by necropsy, morphometrics, and by microscopic examination
      of gonads, livers, spleens and kidneys. Routine, haematoxylin and eosin and/or
      Pearl's reagent-stained paraffin embedded sections were studied by light
      microscopy. Our results provide the first data on the morphometric and
      morphological characteristics of MMC in viscera of apparently healthy free
      ranging sharks from the northwestern Atlantic.

PMID- 19602093
TI  - Identification and pathogenicity to rainbow trout, Oncorhynchus mykiss (Walbaum),
      of some aeromonads.
AB  - Twelve strains of fish pathogenic aeromonads were identified by 16S rRNA
      sequencing as Aeromonas bestiarum, A. hydrophila, A. hydrophila subsp. dhakensis,
      A. salmonicida subsp. salmonicida, A. sobria biovar sobria and A. veronii biovar
      sobria. Following intramuscular injection, A. hydrophila subsp. dhakensis caused
      dark liquefying, raised furuncle-like lesions in rainbow trout within 48 h.
      Extracellular products of all cultures contained gelatinase and lecithinase, and
      most revealed lipase. Congo red absorption and siderophore production was
      recorded, but not so the suicide phenomenon or slime production. Sodium dodecyl
      sulphate polyacrylamide gel electrophoresis profile of the outer membrane
      proteins (OMP) revealed 10-25 bands, of which major bands were seen in the region
      of 32.5-47.5 and 62-83 kDa. Marked heterogenicity of the OMP and whole cell
      protein (WCP) profiles within and among the species was observed. Polypeptides of
      83-173 kDa were detected in the WCP profile of the cultures, but they were not
      expressed in OMP fractions.

PMID- 19602091
TI  - Increased survival by feeding tetradecylthioacetic acid during a natural outbreak
      of heart and skeletal muscle inflammation in S0 Atlantic salmon, Salmo salar L.
AB  - We have previously documented increased survival by feeding tetradecylthioacetic
      acid (TTA) during a natural outbreak of infectious pancreatic necrosis in post
      smolt S1 Atlantic salmon. The aim of the present study was to test the effects of
      dietary TTA in S0 smolt at a location where fish often experience natural
      outbreaks of heart and skeletal muscle inflammation (HSMI) during their first
      spring at sea. The experimental groups were fed a diet supplemented with 0.25%
      TTA for a 6-week period prior to a natural outbreak of HSMI in May 2007. Relative
      percent survival for the groups fed TTA was 45% compared with control diets,
      reducing mortality from 4.7% to 2.5%. Expression of genes related to lipid
      oxidation was higher in cardiac ventricles from salmon fed TTA compared with
      controls. In addition, salmon fed TTA had periodically reduced levels of plasma
      urea, and increased cardiosomatic index and growth. Reduced mortality and
      increased growth after administration of TTA may be related to a combination of
      anti-inflammatory effects, and an altered metabolic balance with better protein
      conservation because of increased lipid degradation.

PMID- 19602094
TI  - In vitro efficacy of praziquantel against the cercariae of Diplostomum sp.,
      Rhipidocotyle fennica and R. campanula.

PMID- 19602095
TI  - Molecular differentiation of infectious pancreatic necrosis virus isolates from
      farmed and wild salmonids in Ireland.
AB  - This study investigated the genotypes and sub-groups of infectious pancreatic
      necrosis virus (IPNV) present in farmed and wild salmonid fish in Ireland. An
      1100-bp portion of the VP2 region of segment A from each of 55 IPNV isolates
      collected over 2003-2007 was amplified by reverse-transcription-polymerase chain
      reaction and the product directly sequenced. The nucleotide sequences of each
      isolate were aligned and compared with each other and with the corresponding
      sequences of a number of reference isolates. All the 55 sequenced isolates
      belonged to genogroup 5 (Sp serotype) and could be divided into two subgroups.
      Irish subgroup 1 consisted of isolates from farmed salmon originating from an
      Irish salmon broodstock. Irish subgroup 2 consisted of isolates from imported
      farmed stock and all reported clinical outbreaks of IPN were associated with
      isolates from subgroup 2. Isolates from wild fish were identical to some isolates
      from subgroup 2, and therefore are believed to have originated from infected
      farms. These results highlight the importance of import risk analysis for
      diseases not listed under current legislation.

PMID- 19602096
TI  - Caspase-dependent induction of apoptosis in barramundi, Lates calcarifer (Bloch),
      muscle cells by grouper iridovirus.
AB  - We recently reported that grouper iridovirus (GIV) can induce apoptosis in
      barramundi, Lates calcarifer, muscle (BM) and swim bladder (BSB) cell lines. In
      this paper, we further characterize the molecular mechanism underlying apoptotic
      death in BM cells triggered by GIV. DNA-laddering and apoptotic cells were
      observed in BM cells infected with UV-irradiated or untreated GIV but was absent
      in cells infected with heat-inactivated GIV, indicating the involvement of viral
      protein in the apoptosis event. In GIV-infected BM cells, the conversion of
      procaspase-3 to caspase-3 was evident and the level of caspase-8 and -9 increased
      as early as 30 min post-infection. When treated with a pancaspase inhibitor, the
      GIV-induced apoptosis event was abolished. These observations indicate that GIV
      induced apoptosis is caspase-dependent, and that both the external and internal
      routes in the caspase-dependent pathway are likely involved in the apoptosis
      process.

PMID- 19602097
TI  - Comparison of the resistance of selected families of common carp, Cyprinus carpio
      L., to koi herpesvirus: preliminary study.

PMID- 19602099
TI  - Calibration of T-Scan sensors for recording bite forces in denture patients.
AB  - Although measurement of maximum voluntary biting force is an important indicator
      of health of the masticatory system, few commercially available transducers have
      been validated for routine clinical use. The T-Scan III system records
      distribution of relative forces around the tooth row during clenching, but not
      absolute forces. This study assesses the reliability of T-Scan sensors with and
      without protection materials and develops calibration curves that allow
      measurement of absolute forces with the T-Scan III.

PMID- 19602098
TI  - Organ and gestational age effects of maternal nutrient restriction on global
      methylation in fetal baboons.
AB  - BACKGROUND: A sub-optimal intrauterine environment alters the trajectory of fetal
      development with profound effects on life-time health. Altered methylation, a
      proposed epigenetic mechanism responsible for these changes, has been studied in
      non-primate species but not nonhuman primates. We tested the hypotheses that
      global methylation in fetal baboon demonstrates organ specificity, gestational
      age specificity, and changes with maternal nutritional status. METHODS: We
      measured global DNA methylation in fetuses of control fed (CTR) and nutrient
      restricted mothers fed 70% of controls (MNR) for brain, kidney, liver and heart
      at 0.5 and 0.9 gestation (G). RESULTS: We observed organ and gestation specific
      changes that were modified by maternal diet. Methylation in CTR fetuses was
      highest in frontal cortex and lowest in liver. MNR decreased methylation in 0.5G
      kidney and increased methylation in 0.9G kidney and frontal cortex. CONCLUSION:
      These results demonstrate a potential epigenetic mechanism whereby reduced
      maternal nutrition has long-term programming effects on fetal organ development.

PMID- 19602100
TI  - Use of sonographic elastography of the masseter muscles for optimizing massage
      pressure: a preliminary study.
AB  - To examine the stiffness of the masseter muscle using sonographic elastography
      and to investigate its relationship with the most comfortable massage pressure in
      the healthy volunteers. In 16 healthy volunteers (10 men and 6 women), the
      Masseter Stiffness Index (MSI) was measured using EUB-7000 real-time tissue
      elastography. They underwent massages at three kinds of pressures using the Oral
      Rehabilitation Robot (WAO-1). A subjective evaluation regarding the comfort of
      each massage was recorded on the visual analogue scale. Elastography was also
      performed in two patients with temporomandibular joint dysfunction with the
      myofascial pain. The mean MSI of the right and left muscles in the healthy
      volunteers were 0.85 +/- 0.44 and 0.74 +/- 0.35 respectively. There was no
      significant difference between the right and left MSI in the healthy volunteers.
      The MSI was related to massage pressure at which the healthy men felt most
      comfortable. The two temporomandibular disorder patients had a large laterality
      in the MSI. The MSI was related to the most comfortable massage pressure in the
      healthy men. The MSI can be one index for determining the massage pressure.

PMID- 19602101
TI  - A glucocorticoid sensitive biphasic rhythm of testosterone secretion.
AB  - Studies of the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic
      pituitary-testicular (HPT) axis have revealed a reciprocal relationship between
      these two endocrine pathways. In rats, for example, disruption of the HPT axis
      alters the circadian secretion of corticosterone. Stress, on the other hand, can
      have varying effects on testosterone secretion in both rats and humans.
      Furthermore, in contrast to humans, where several pulses of testosterone
      secretion can be detected across the 24-h period with the largest in the morning,
      rats appear to exhibit a diurnal rhythm of testosterone secretion. In the present
      study, we used an automated blood sampling system to investigate the true
      circadian pattern of testosterone secretion under basal conditions and
      investigated how this responds to changes in levels of circulating
      corticosteroids. Analysis of plasma testosterone revealed the expected bimodal
      pattern of basal testosterone secretion. The two secretory episodes were 12.59 h
      +/- 41 min apart and 4.04 h +/- 16 min long, with one in the light phase and the
      other in the dark phase of the cycle. Interestingly, when both testosterone and
      corticosterone diurnal profile were compared, we found that the circadian rise in
      plasma corticosterone levels falls neatly between the two testosterone secretory
      episodes. Treatment of rats with the synthetic glucocorticoid methylprednisolone
      in their drinking water abolished the normal bimodal profile of testosterone
      secretion. These rats show transient pulses of testosterone throughout the 24 h,
      but no circadian pattern. By contrast, adrenalectomised rats maintain their
      bimodal circadian pattern, suggesting that an intact HPA axis is not necessary
      for generation of the endogenous HPT rhythm. Thus, although the circadian rhythm
      of testosterone does not depend on normal HPA function, increased levels of
      glucocorticoids can abolish normal HPT rhythmicity.

PMID- 19602102
TI  - Hypothalamic-pituitary-adrenal axis abnormalities in response to deletion of
      11beta-HSD1 is strain-dependent.
AB  - Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis
      activity underlie differential vulnerability to neuropsychiatric and metabolic
      disorders, although the basis of this variation is poorly understood. 11beta
      Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has previously been shown to
      influence HPA axis activity. 129/MF1 mice null for 11beta-HSD1 (129/MF1 HSD1(-/
      )) have greatly increased adrenal gland size and altered HPA activity, consistent
      with reduced glucocorticoid negative feedback. On this background, concentrations
      of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in
      unstressed mice, and showed a delayed return to baseline after stress in HSD1
      null mice with reduced sensitivity to exogenous glucocorticoid feedback compared
      to same-background genetic controls. In the present study, we report that the
      genetic background can dramatically alter this pattern. By contrast to HSD1(-/-)
      mice on a 129/MF1 background, HSD1(-/-) mice congenic on a C57Bl/6J background
      have normal basal plasma corticosterone and ACTH concentrations and exhibit
      normal return to baseline of plasma corticosterone and ACTH concentrations after
      stress. Furthermore, in contrast to 129/MF1 HSD1(-/-) mice, C57Bl/6J HSD1(-/-)
      mice have increased glucocorticoid receptor expression in areas of the brain
      involved in glucocorticoid negative feedback (hippocampus and paraventricular
      nucleus), suggesting this may be a compensatory response to normalise feedback
      control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1(-/-) mice
      show increased sensitivity to dexamethasone-mediated suppression of peak
      corticosterone. Thus, although 11beta-HSD1 appears to contribute to regulation of
      the HPA axis, the genetic background is crucial in governing the response to (and
      hence the consequences of) its loss. Similar variations in plasticity may
      underpin inter-individual differences in vulnerability to disorders associated
      with HPA axis dysregulation. They also indicate that 11beta-HSD1 inhibition does
      not inevitably activate the HPA axis.

PMID- 19602104
TI  - Comparison of the differences in cephalometric parameters after active
      orthodontic treatment applying mini-screw implants or transpalatal arches in
      adult patients with bialveolar dental protrusion.
AB  - The purpose of this study was to compare the differences in cephalometric
      parameters after active orthodontic treatment applying mini-screw implants (G1)
      or transpalatal arches (G2) as anchorage in adult patients with bialveolar dental
      protrusion needing extraction of four premolars. A total of 34 Chinese patients
      (18-33 years) with bialveolar dental protrusion were randomly assigned to G1 and
      G2. Sliding mechanics and en-masse retraction of anterior teeth were applied to
      close extraction spaces. The changes in skeletal, dental and soft tissues were
      analyzed in both groups on lateral cephalograms before and after active
      orthodontic treatment. Independent samples and paired-samples t-tests were
      utilized to analyze the morphological changes in both groups. ANB angle was
      decreased in G1 and remained unchanged in G2 (P < 0.05). Upper incisors were
      retracted more in G1 than in G2 (P < 0.01). Upper incisors and molars were
      intruded in G1, but extruded in G2 (P < 0.01). Although the upper molars were
      found with no significant distalization (P > 0.05), there existed molars
      distalization in some patients. However, the maxillary molars in G2 were
      mesialized (P < 0.01). The intrusion of upper molars in G1 resulted in
      counterclockwise rotation of the mandible and decrease of SN-MP angle (P < 0.01).
      Upper lip linear measurements including UL-Y and UL-E were decreased more in G1
      than in G2 (P < 0.05). Mini-screw implants provide absolute anchorage in vertical
      and sagittal directions. Better dental, skeletal and soft tissue changes could be
      achieved by mini-screw implants especially in hyperdivergent patients. Skeletal
      anchorage should be routinely recommended in patients with bialveolar dental
      protrusion.

PMID- 19602103
TI  - Huntington's disease does not appear to increase the risk of diabetes mellitus.
AB  - Huntington's disease (HD) is an autosomal, dominantly inherited,
      neurodegenerative disorder characterised by neurological, cognitive and
      psychiatric symptoms. HD has been associated with diabetes mellitus, which is, to
      some extent, supported by studies in transgenic HD mice. In transgenic mice, the
      severity of the diabetic phenotype appears to correlate with the length of a
      polyglutamine expansion in the protein huntingtin. In the present study, we
      investigated the association between diabetes mellitus and HD by performing an
      oral glucose-tolerance test (OGTT) to evaluate the glucose-tolerance status and
      OGTT-related insulin release in 14 HD patients. Furthermore, we expressed N
      terminal huntingtin fragments with different polyglutamine lengths in an
      insulinoma-cell line (INS-1E) to investigate how mutant huntingtin influences
      glucose-stimulated insulin release in vitro. We found no difference between a
      group of early- and middle-stage HD patients and a large group of control
      individuals in any of the assessed variables. However, the glucose-stimulated
      induction of insulin release was significantly reduced in the insulinoma-cell
      line expressing highly expanded huntingtin compared to cells expressing
      huntingtin with modestly elongated polyglutamine stretches. These data indicate
      that insulin release from beta-cells expressing mutant huntingtin appears to be
      polyglutamine length-dependent, and that polyglutamine lengths within the range
      normally found in adult onset HD do not influence insulin release. This
      challenges the assumption of an increased risk of diabetes among HD patients,
      although our results do not exclude a changed glucose tolerance in end-stage HD
      patients or in patients with juvenile onset HD. It also raises the question of
      which extent transgenic mice models reflect the pathology of human HD in this
      regard.

PMID- 19602106
TI  - A quinol peroxidase inhibitor prevents secretion of a leukotoxin from
      Aggregatibacter actinomycetemcomitans.
AB  - BACKGROUND AND OBJECTIVE: Quinol peroxidase (QPO) catalyzes peroxidase activity
      using quinol in the respiratory chain as a substrate. Quinol peroxidase is
      essential for the secretion of leukotoxin (LtxA), which destroys leukocytes and
      erythrocytes in humans and is one of the major virulence factors of
      Aggregatibacter actinomycetemcomitans, which is associated with localized
      aggressive periodontitis. In the present study, we aimed to find a highly potent
      QPO inhibitor to attenuate the virulence of A. actinomycetemcomitans. MATERIAL
      AND METHODS: For screening of QPO inhibitors, QPO activity was measured
      kinetically by SpectraMax Plus with 96-well UV plates. Three hundred compounds in
      the Kitasato Institute for Life Sciences Chemical Library were screened.
      Secretion of LtxA in the culture supernatant was examined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Cytotoxicity against human
      promyelocytic leukemia cell line (HL-60) cells from the culture supernatant was
      measured by Trypan Blue exclusion test. RESULTS: The present study characterized
      ascofuranone as a highly potent inhibitor of QPO (K(i) = 9.557 +/- 0.865 nm).
      Ascofuranone inhibited secretion of LtxA by A. actinomycetemcomitans in a dose
      dependent manner, making A. actinomycetemcomitans less pathogenic to HL-60 cells.
      CONCLUSION: Quinol peroxidase inhibitors are promising candidates as alternative
      drugs for the treatment and prevention of the onset of localized aggressive
      periodontitis. Using ascofuranone as a seed compound, further study of QPO
      inhibitors could provide novel chemotherapeutic strategies for controlling
      localized aggressive periodontitis.

PMID- 19602105
TI  - Effects of topical application of lipopolysaccharide and proteases on hepatic
      injury induced by high-cholesterol diet in rats.
AB  - BACKGROUND AND OBJECTIVE: Topical application of lipopolysaccharide and proteases
      to the gingival sulcus induced not only periodontal inflammation but also
      detectable liver changes in rats fed a normal diet. However, these changes in the
      liver were not sufficient to induce pathological consequences. The purpose of the
      present study was to investigate whether gingival inflammation-induced liver
      change would have more dramatic pathological consequences in rats fed a high
      cholesterol diet compared with the effect of the high-cholesterol diet alone.
      MATERIAL AND METHODS: Twenty-four male Wistar rats were divided into four groups.
      During an 8 week experimental period, two groups were fed a normal diet and the
      other two were fed a high-cholesterol diet containing 1% cholesterol (w/w) and
      0.5% cholic acid (w/w). Four weeks prior to the end of the experimental period,
      one of each of the dietary groups received daily topical application of
      lipopolysaccharide and proteases to the gingival sulcus, while the other was
      treated with pyrogen-free water. RESULTS: In the rats without application of
      lipopolysaccharide and proteases, the serum level of hexanoyl-lysine, scores of
      steatosis and inflammation, and concentration of 8-hydroxydeoxyguanosine in liver
      of rats fed a high-cholesterol diet were higher than in those fed a normal diet.
      In rats fed a high-cholesterol diet, the scores of steatosis and inflammation and
      the concentration of 8-hydroxydeoxyguanosine in the liver of rats with
      application of lipopolysaccharide and proteases were higher than in those
      without. CONCLUSION: In a rat model, application of lipopolysaccharide and
      proteases to the gingival sulcus augmented the effect of a high-cholesterol diet
      on steatosis, inflammation and oxidative damage in the liver.

PMID- 19602107
TI  - Periodontitis-associated up-regulation of systemic inflammatory mediator level
      may increase the risk of coronary heart disease.
AB  - BACKGROUND AND OBJECTIVE: Although an elevation in the concentration of high
      sensitivity C-reactive protein (hs-CRP) as a result of periodontal infection may
      account for an increased risk of developing coronary heart disease (CHD), the
      effect of periodontal infection on the level of hs-CRP in an otherwise healthy
      Japanese population has not yet been reported. The aim of the present study was
      to confirm, on a larger scale, our previous pilot study findings that both
      chronic periodontitis and subsequent periodontal treatment alter the serum levels
      of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha). MATERIAL AND METHODS: The concentrations of serum hs-CRP, IL-6 and
      TNF-alpha were measured in 78 periodontitis patients at baseline and at re
      assessment, and in 40 periodontally healthy subjects at the time of examination.
      RESULTS: The concentrations of hs-CRP and IL-6 in the sera of periodontitis
      patients were significantly higher than those in control subjects. By contrast,
      the concentration of TNF-alpha was significantly lower in periodontitis patients
      than in control subjects. Whereas periodontal treatment decreased the levels of
      serum hs-CRP and IL-6, no such effect was observed for TNF-alpha. When the
      patients were subdivided into four groups according to their initial
      concentration of hs-CRP, only the CRP and IL-6 concentrations of the highest
      quartile group showed a significant reduction following periodontal treatment. No
      significant difference in the initial clinical parameters was observed in any
      quartile. CONCLUSION: Although periodontal infection does affect the
      concentration of hs-CRP and IL-6 in serum, a subgroup of patients exist who are
      highly susceptible to an increased risk of CHD associated with periodontitis,
      suggesting that there may be subjects who have an elevated risk of CHD
      independent of susceptibility to periodontal tissue destruction per se.

PMID- 19602108
TI  - Effect of matrix metalloproteinase-1 promoter genotype on interleukin-1beta
      induced matrix metalloproteinase-1 production in human periodontal ligament
      cells.
AB  - BACKGROUND AND OBJECTIVE: Our previous studies have shown that a single
      nucleotide polymorphism at nucleotide -1607 of the human matrix metalloproteinase
      1 (MMP-1) promoter is associated with the severity of periodontal disease. The
      purpose of this study was to evaluate the effect of different MMP-1 promoter
      genotypes on interleukin-1beta-induced MMP-1 production in human periodontal
      ligament cells. MATERIAL AND METHODS: Periodontal ligament cells from 16
      different subjects were cultured. Restriction fragment length polymorphism
      polymerase chain reaction was used to identify the MMP-1 promoter genotype of
      periodontal ligament cells. Periodontal ligament cells were stimulated with
      phorbol 12-myristate 13-acetate/interleukin-1beta. Reverse transcription
      polymerase chain reaction amplifications and enzyme linked immunosorbent assays
      were then utilized to determine the MMP-1 mRNA levels and to assess the
      concentration of MMP-1 protein, respectively. RESULTS: The results showed that
      cells with the 1G/2G and the 2G/2G genotype produced higher amounts of MMP-1
      protein than cells with the 1G/1G genotype. Induction of MMP-1 mRNA as a result
      of stimulation with interleukin-1beta was significantly increased in cells with a
      1G/2G or a 2G/2G genotype compared with cells homozygous for the 1G allele.
      CONCLUSION: The results of the present study suggest that the single nucleotide
      polymorphism at nucleotide -1607 of the human MMP-1 promoter might influence the
      interleukin-1beta-induced expression of MMP-1 in periodontal ligament cells.

PMID- 19602110
TI  - Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer
      cardioprotection and improve recovery of the electrically induced intracellular
      calcium transient during ischemia and reperfusion.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis lipopolysaccharide (LPS) is a
      ligand for cell surface toll-like receptors (TLR), TLR2 and TLR4 while
      stimulation of either leads to cardioprotection. We hypothesized that: (1)
      pretreatment with P. gingivalis LPS at appropriate concentrations would induce
      cardioprotection against injury induced by ischemia and reperfusion; and (2) P.
      gingivalis LPS pretreatment at cardioprotective concentrations may reduce Ca(2+)
      overload, which is a precipitating cause of injury, and improve recovery of
      contractile function. MATERIAL AND METHODS: Male Sprague-Dawley rats were
      randomly selected to receive intraperitoneal saline or hot phenol-water-extracted
      P. gingivalis LPS at 0.2, 0.5, 1.0, 2.0 or 4.0 mg/kg 24 h before the experiment.
      The hearts were isolated and subjected to regional ischemia by coronary artery
      ligation followed by reperfusion. In isolated rat ventricular myocytes, the
      cytosolic Ca(2+) level and the electrically induced intracellular calcium
      (E[Ca(2+)](i)) transient, which reflects contractile function, were determined
      after pretreatment with a cardioprotective dose of P. gingivalis LPS. RESULTS:
      Pretreatment with 0.5 mg/kg P. gingivalis LPS significantly reduced, while
      pretreatment with 1.0-4.0 mg/kg significantly increased infarct size. The Ca(2+)
      overload induced by ischemia-reperfusion was attenuated in myocytes from rats
      pretreated with 0.5 mg/kg P. gingivalis LPS. Pretreated myocytes also showed an
      increased amplitude of the E[Ca(2+)](i) transient, no prolongation of the time to
      reach the peak E[Ca(2+)](i) transient and shorter 50% decay time during
      reperfusion. CONCLUSION: At a dosage of 0.5 mg/kg, P. gingivalis LPS confers
      cardioprotection against ischemia-reperfusion-induced injury and improved
      intracellular E[Ca(2+)](i) transient recovery, hence improving myocyte
      contractile recovery.

PMID- 19602109
TI  - A novel murine model for chronic inflammatory alveolar bone loss.
AB  - BACKGROUND AND OBJECTIVE: Chronic inflammatory bowel disease (IBD) demonstrates
      some similarities to the dysregulated chronic immunoinflammatory lesion of
      periodontitis. Trinitrobenzene sulphonic acid (TNBS) and dextran sodium sulphate
      (DSS) administered to rodents have been shown to elicit inflammatory responses
      that undermine the integrity of the gut epithelium in a similar manner to IBD in
      humans. The objective of this study was to evaluate the ability of these
      chemicals to elicit periodontal inflammation as a novel model for alveolar bone
      loss. MATERIAL AND METHODS: Mice were treated by oral application of TNBS twice a
      week, or with DSS in the diet over a period of 18 weeks. Alveolar bone loss was
      assessed on the defleshed skull using morphometric measures for area of bone
      resorption. RESULTS: The TNBS-treated animals tolerated oral administration with
      no clinical symptoms and gained weight at a similar rate to normal control
      animals. In contrast, DSS exerted a systemic response, including shortening of
      colonic tissue and liver enzyme changes. Both TNBS and DSS caused a localized
      action on periodontal tissues, with alveolar bone loss observed in both maxilla
      and mandibles, with progression in a time-dependent manner. Bone loss was
      detected as early as week 7, with more severe periodontitis increasing over the
      18 weeks (p < 0.001). Young (7-month-old) and old (12-month-old) mice with severe
      combined immunodeficiency were treated with TNBS for a period of 7 weeks and did
      not develop significant bone loss. CONCLUSION: These data show that oral
      administration of TNBS or DSS provokes alveolar bone loss in concert with the
      autochthonous oral microbiota.

PMID- 19602111
TI  - Epidermal growth factor released from platelet-rich plasma promotes endothelial
      cell proliferation in vitro.
AB  - BACKGROUND AND OBJECTIVE: The therapeutic benefits of platelet-rich plasma (PRP)
      for the promotion of healing and regeneration of periodontal tissues are thought
      to result from enrichment in growth factors released from platelets. The aim of
      this study was to evaluate the effects of specific growth factors released from
      PRP on endothelial cell proliferation. MATERIAL AND METHODS: The levels of
      vascular endothelial growth factor (VEGF), platelet-derived growth factor BB
      (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor
      (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five
      donors were quantified by enzyme-linked immunosorbent assay. Supernatants were
      treated with neutralizing antibodies specific to each growth factor, and the
      effects of these treatments on human umbilical vein endothelial cell (HUVEC)
      proliferation in vitro were determined. The effect of removing EGF from PRP
      supernatants with antibody-coated beads on HUVEC proliferation was also tested.
      RESULTS: Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP
      supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of
      EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC
      proliferation (up to 40%), while such an inhibition was not observed following
      neutralization of the other growth factors. Removal of EGF from PRP supernatants
      by treatment with antibody-coated beads also resulted in a significant decrease
      in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in
      a dose-dependent manner. CONCLUSION: This study showed that PRP supernatants are
      highly mitogenic for endothelial cells and provided evidence that this effect may
      be due, at least in part, to the presence of EGF. In vivo experiments are needed
      to confirm the roles of specific growth factors released from PRP in the healing
      of oral surgical and/or periodontal wounds.

PMID- 19602112
TI  - A multiplex immunoassay demonstrates reductions in gingival crevicular fluid
      cytokines following initial periodontal therapy.
AB  - BACKGROUND AND OBJECTIVE: Cytokines and chemokines play an important role in the
      pathogenesis of periodontal diseases. The objective of this study was to
      quantitatively assess the effect of initial periodontal therapy on gingival
      crevicular fluid levels of a comprehensive panel of cytokines and chemokines,
      including several less extensively studied mediators. MATERIAL AND METHODS:
      Clinical examinations were performed and gingival crevicular fluid samples
      obtained from six subjects with generalized severe chronic periodontitis prior to
      initial periodontal therapy and at re-evaluation (6-8 weeks). Four diseased and
      two healthy sites were sampled in each subject. Twenty-two gingival crevicular
      fluid mediators were examined using a multiplex antibody capture and detection
      platform. Statistical analyses were performed by fitting mixed effects linear
      models to log-transformed gingival crevicular fluid values. RESULTS: Gingival
      crevicular fluid interleukin (IL)-1alpha and IL-1beta were the only cytokines to
      differ in initially diseased vs. initially healthy sites. Following initial
      therapy, 13 of the 16 detectable cytokines and chemokines decreased significantly
      in diseased sites, including IL-1alpha, IL-1beta, IL-2, IL-3, IL-6, IL-7, IL-8,
      IL-12 (p40), CCL5/regulated on activation, normally T cell expressed and secreted
      (RANTES), eotaxin, macrophage chemotactic protein-1, macrophage inflammatory
      protein-1alpha and interferon-gamma. At healthy sites, only three of the 16
      mediators were significantly altered following therapy. CONCLUSION: This is the
      first study, to our knowledge, to evaluate such an extensive panel of gingival
      crevicular fluid mediators within the same sample prior to and following initial
      therapy. The results confirm that periodontal therapy effectively reduces pro
      inflammatory cytokines and chemokines, including less well-described mediators
      that may be important in initiation and progression of periodontitis. The
      multiplex assay will prove useful for future gingival crevicular fluid studies.

PMID- 19602113
TI  - Shosaikoto increases calprotectin expression in human oral epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: Oral epithelial cells help to prevent against bacterial
      infection in the oral cavity by producing antimicrobial peptides (AMPs). A broad
      spectrum AMP, calprotectin (a complex of S100A8 and S100A9 proteins), is
      expressed by oral epithelial cells and is up-regulated by interleukin-1alpha (IL
      1alpha). Shosaikoto (SST) is a traditional Japanese herbal medicine that has
      immunomodulatory effects and is reported to enhance the levels of IL-1alpha in
      epithelial cells. The purpose of this study was to investigate the effect of SST
      on the expression of calprotectin and other AMPs through the regulation of IL
      1alpha in oral epithelial cells. MATERIAL AND METHODS: Human oral epithelial
      cells (TR146) were cultured with SST (at concentrations ranging from 10 to 250
      microg/mL) in the presence or absence of anti-IL-1alpha or IL-1 receptor
      antagonist. The expression of S100A8- and S100A9-specific mRNAs was examined by
      northern blotting. Calprotectin expression and IL-1alpha secretion were
      investigated by immunofluorescent staining or ELISA. The expression of other AMPs
      and IL-1alpha was analyzed by RT-PCR and by quantitative real-time PCR. RESULTS:
      Shosaikoto (25 microg/mL) significantly increased the expression of S100A8- and
      S100A9-specific mRNAs and calprotectin protein. Shosaikoto increased S100A7
      expression, but had no effect on the expression of other AMPs. The expression of
      IL-1alpha-specific mRNA and its protein were slightly increased by SST. A
      neutralizing antibody against IL-1alpha or IL-1 receptor antagonist inhibited SST
      up-regulated S100A8/S100A9 mRNA expression. CONCLUSION: These results suggest
      that SST increases the expression of calprotectin and S100A7 in oral epithelial
      cells. In response to SST, up-regulation of calprotectin may be partially induced
      via IL-1alpha.

PMID- 19602114
TI  - Hydrogen sulfide induces apoptosis in human periodontium cells.
AB  - BACKGROUND AND OBJECTIVE: The existence of hydrogen sulfide (H(2)S) at high
      concentrations in periodontal pockets is a characteristic feature of
      periodontitis. Periodontal pathogens play a key role in the production of H(2)S
      under these etiology conditions. This study was designed to examine the
      cytotoxicity of H(2)S in periodontium cells, including human periodontal ligament
      (PDL) cells and human gingival fibroblasts (HGFs), as well as the role of H(2)S
      in apoptosis induction. MATERIAL AND METHODS: Human PDL cells and HGFs were
      cultured in the presence of Na(2)S/HCl or in the presence of H(2)S produced
      enzymatically by the action of Treponema denticola cystalysin (l-cysteine
      desulfhydrase) on l-cysteine. Apoptosis was assessed morphologically after
      nuclear staining with DAPI or was quantified by flow cytometry after staining
      with annexin V. Caspase activation was measured by an enzymatic assay using DEVD
      AMC, a synthetic caspase substrate. RESULTS: Among the three products obtained
      following degradation of l-cysteine by T. denticola cystalysin, only H(2)S
      induced significant apoptosis in HGF cells. Hydrogen sulfide also induced typical
      apoptotic morphology in cultured PDL cells. The changes were dependent on the
      H(2)S dose and on the treatment time with H(2)S. Hydrogen sulfide-induced
      apoptosis was also confirmed by staining with annexin V and propidium iodide. In
      addition, treatment with H(2)S led to caspase activation in these cells.
      CONCLUSION: These results showed that physiological concentrations of H(2)S can
      induce apoptosis of PDL cells and HGFs in periodontitis, suggesting that H(2)S
      may play an important role in periodontal tissue damage in periodontal diseases.

PMID- 19602115
TI  - Oral malodorous compound triggers mitochondrial-dependent apoptosis and causes
      genomic DNA damage in human gingival epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: Volatile sulfur compounds are the main compounds
      causing halitosis. One of these compounds, hydrogen sulfide (H(2)S), which is
      responsible for physiological halitosis, is reported also to have periodontal
      pathogenic activities. Hydrogen sulfide has been shown to activate the apoptotic
      process in different tissues. Apoptosis plays an important role in the
      development of periodontitis. The aim of this study was to determine whether
      H(2)S causes apoptosis in human gingival epithelial cells and to examine the
      cellular signaling pathway initiating the process. MATERIAL AND METHODS: Human
      gingival epithelial cells were incubated with 50 ng/mL H(2)S in air contining 5%
      CO(2) for 24, 48 or 72 h. To detect apoptosis, the cells were stained with
      annexin V and 7-amino actinomycin D, and analyzed using flow cytometry. Reactive
      oxygen species, mitochondrial membrane depolarization and release of cytochrome C
      into the cytosol were assessed using flow cytometry and enzyme-linked
      immunosorbent assay. Activity levels for the key apoptotic enzymes caspase-9, -8
      and -3 were also determined. Genomic DNA damage was detected using single-cell
      gel electrophoresis. RESULTS: Apoptosis was significantly increased to 24.5 +/-
      5.7 at 24 h and 41.5 +/- 8.9% at 48 h (p < 0.01). Reactive oxygen species were
      enhanced and mitochondrial membrane depolarization was collapsed. Cytochrome C
      release was dramatically increased (0.12 +/- 0.02 vs. 0.02 +/- 0.01 at 24 h and
      0.21 +/- 0.02 vs. 0.02 +/- 0.01 ng/mL at 48 h; p < 0.05). Caspase-9 and -3 were
      strongly activated, while caspase-8 activity remained low. The percentage of DNA
      strand breaks increased, especially at 48 h. CONCLUSION: Hydrogen sulfide induces
      apoptosis in human gingival epithelial cells by activating the mitochondrial
      pathway.

PMID- 19602117
TI  - Host beta-globin gene fragments in crevicular fluid as a biomarker in periodontal
      health and disease.
AB  - BACKGROUND AND OBJECTIVE: Leukocytes and epithelium are the first line of defense
      in preventing bacterial invasion into periodontium. Some of these cells die in
      gingival crevicular fluid, whereupon their DNA is spilled out. The present study
      was designed to investigate the profile of host beta-globin gene fragments in the
      gingival crevicular fluid of various periodontal conditions. MATERIAL AND
      METHODS: Gingival crevicular fluid from 40 teeth with chronic periodontitis, 30
      with gingivitis and 22 that were clinically healthy were centrifuged (3,000 g, 10
      min). The supernatant (cell-free gingival crevicular fluid) was centrifuged again
      (13,000 g, 10 min), resulting in the pellet and the supernatant as debris and
      debris-free fractions, respectively. Specific primers for amplifying 110 bp, 536
      bp and 2 kb amplicons of human beta-globin gene were used to investigate host DNA
      by quantitative and qualitative polymerase chain reaction. RESULTS: The
      periodontitis group showed the largest amount of host beta-globin gene fragments,
      while the healthy group had the lowest. In the debris and debris-free fractions,
      the 536 bp and 2 kb amplicons were more often detected in the periodontitis group
      than in the other groups. Interestingly, the presence of 2 kb amplicon in the
      debris fraction could be used to discriminate periodontitis from gingivitis and
      healthy groups because we found it in 85% of periodontitis samples but only in
      13% of gingivitis samples, and it was absent in the healthy group. CONCLUSION:
      This study shows the different DNA profiles of cell-free gingival crevicular
      fluid in periodontal health and disease. It suggests that the quantity and
      quality of host DNA are dependent on the disease conditions. Therefore, the beta
      globin gene fragments in cell-free gingival crevicular fluid may be a potential
      biomarker of periodontal disease progression.

PMID- 19602116
TI  - Green tea catechin inhibits lipopolysaccharide-induced bone resorption in vivo.
AB  - BACKGROUND AND OBJECTIVE: Bone resorption is positively regulated by receptor
      activator of nuclear factor-kappaB ligand (RANKL). Pro-inflammatory cytokines,
      such as interleukin (IL)-1beta, promote RANKL expression by stromal cells and
      osteoblasts. Green tea catechin (GTC) has beneficial effects on human health and
      has been reported to inhibit osteoclast formation in an in vitro co-culture
      system. However, there has been no investigation of the effect of GTC on
      periodontal bone resorption in vivo. We therefore investigated whether GTC has an
      inhibitory effect on lipopolysaccharide (LPS)-induced bone resorption. MATERIAL
      AND METHODS: Escherichia coli (E. coli) LPS or LPS with GTC was injected a total
      of 10 times, once every 48 h, into the gingivae of BALB/c mice. Another group of
      mice, housed with free access to water containing GTC throughout the experimental
      period, were also injected with LPS in a similar manner. RESULTS: The alveolar
      bone resorption and IL-1beta expression induced by LPS in gingival tissue were
      significantly decreased by injection or oral administration of GTC. Furthermore,
      when GTC was added to the medium, decreased responses to LPS were observed in
      CD14-expressing Chinese hamster ovary (CHO) reporter cells, which express CD25
      through LPS-induced nuclear factor-kappaB (NF-kappaB) activation. These findings
      demonstrated that GTC inhibits nuclear translocation of NF-kappaB activated by
      LPS. In addition, osteoclasts were generated from mouse bone marrow macrophages
      cultured in a medium containing RANKL and macrophage colony-stimulating factor
      with or without GTC. The number of osteoclasts was decreased in dose-dependent
      manner when GTC was added to the culture medium. CONCLUSION: These results
      suggest that GTC suppresses LPS-induced bone resorption by inhibiting IL-1beta
      production or by directly inhibiting osteoclastogenesis.

PMID- 19602118
TI  - Immunohistochemical localization of elastin, fibrillins and microfibril
      associated glycoprotein-1 in the developing periodontal ligament of the rat
      molar.
AB  - BACKGROUND AND OBJECTIVE: Elastic system fibers are a major component of the
      periodontal ligament, but little information is available about their detailed
      composition or the mechanism of elastogenesis in the developing periodontal
      ligament. The purpose of this study was to investigate immunolocalization of
      elastin, fibrillins and microfibril-associated glycoprotein-1 (MAGP-1) in the
      developing periodontal ligament of the rat molar. MATERIAL AND METHODS: Frozen
      sections of demineralized as well as non-demineralized periodontal ligament of
      Wistar rats of various ages from 19 days to 7 weeks were incubated with anti
      elastin, anti-fibrillin-1 and -2 and anti-MAGP-1 antibodies followed by
      peroxidase-conjugated secondary antibodies. After incubation with
      diaminobenzidine solution, immunoreaction products were observed with a light
      microscope. RESULTS: In the developing periodontal ligament of 19-day-old rats,
      fibers immunopositive to elastin were not present, but fibers positively stained
      for fibrillin-2 and MAGP-1 were widely distributed throughout the ligament. The
      latter fibers were arranged in the apico-occlusal direction along with blood
      vessels. In 3-week-old rats, fibers stained for elastin were observed for the
      first time in the apical region of the ligament. The number and distribution
      pattern of these elastin-positive fibers was basically the same as those in rats
      aged 5 and 7 weeks. In contrast, fibrillin-2- and MAGP-1-positive fibers were
      more extensively distributed in the ligament, and their pattern of distribution
      was comparable to that of reported oxytalan fibers. Fibrillin-1 was, however, not
      detected either in demineralized sections or in non-demineralized sections,
      indicating its absence in periodontal ligament. CONCLUSION: Elastin expressed in
      the periodontal ligament assembled into elaunin fibers in the vicinity of blood
      vessels. Both fibrillin-2 and MAGP-1 are structural components not only of the
      elastin-associated microfibrils but also of elastin-free microfibrils, with
      possible roles in elastogenesis and in periodontal ligament homeostasis.

PMID- 19602120
TI  - The association of psychosocial factors and smoking with periodontal health in a
      community population.
AB  - BACKGROUND AND OBJECTIVE: The association between psychosocial factors and
      periodontal disease has been widely reported and might be modified by smoking
      status. This study investigated the association of periodontal status with
      psychosocial factors and smoking in a community population. MATERIAL AND METHODS:
      A structured questionnaire was administered to a total of 1,764 civilian
      noninstitutional (general population excluding from nursing homes, sanitariums
      and hospitals) Taiwanese individuals to assess the presence and severity of
      psychosocial factors [using the 12-item Chinese health questionnaire (CHQ-12)],
      smoking habits and other related factors. Periodontal status was established
      using the community periodontal index and by measuring clinical loss of
      attachment. RESULTS: Psychological factors and smoking were significantly
      associated with loss of attachment (odds ratio = 1.69, 95% confidence interval =
      1.01-2.77, comparing the CHQ-12 score of >or= 6 with the CHQ-12 score of 0-2 and
      p = 0.032 for linear trend; odds ratio = 2.21, 95% confidence interval = 1.45
      3.37, comparing smokers with nonsmokers) but not with community periodontal
      index. The association was found to be stronger among smokers than among
      nonsmokers. Smokers with a CHQ-12 score of >or= 6 had a higher odds ratio of loss
      of attachment (odds ratio = 2.49, 95% confidence interval = 0.91-6.49) than
      nonsmokers (odds ratio = 1.43, 95% confidence interval = 0.76-2.58). For
      periodontal health measured using the community periodontal index, married and
      divorced/widowed subjects tended to have poorer periodontal health (odds ratio =
      3.38, 95% confidence interval = 1.26-10.81 and odds ratio = 3.83, 95% confidence
      interval = 1.21-13.83, respectively) than single subjects among nonsmokers but
      not among smokers. CONCLUSION: Poor mental health had a stronger association with
      periodontal disease among smokers than among nonsmokers, especially in
      accumulative attachment loss. Our findings suggest that mental health and smoking
      might have a synergistic effect on the risk of developing periodontal disease.

PMID- 19602119
TI  - Effects of mechanical stimulation by a powered toothbrush on the healing of
      periodontal tissue in a rat model of periodontal disease.
AB  - BACKGROUND AND OBJECTIVE: Elimination of pathogens is the main aim of periodontal
      treatment; however, modulation of the host immune response should also be
      considered. This study aimed to evaluate the effects of mechanical stimulation on
      periodontal healing in rats. MATERIAL AND METHODS: Before starting the
      experiment, lipopolysaccharide and proteases were applied once a day, for 4 wk,
      to both maxillary first molars of 30 rats to induce periodontal disease, and the
      application was stopped at the end of the 4-wk period. The experiment started
      immediately following this pretreatment. In the experiment, the left palatal
      gingiva was stimulated once daily using a powered toothbrush and the right
      gingiva served as a control (no mechanical stimulation). Pathological changes,
      and proliferation and cell death in periodontal tissues, were evaluated
      histometrically and immunohistochemically at baseline (0 wk), and at 1 and 3 wk
      of stimulation. RESULTS: The control showed a reduction of polymorphonuclear
      leukocyte infiltration in connective tissue and an increase in the numbers of
      gingival and periodontal ligament fibroblasts. Mechanical stimulation reduced
      polymorphonuclear leukocyte infiltration and the area of destroyed collagen in
      connective tissue, and increased the number of gingival fibroblasts; however, it
      had no effect on alveolar bone and root resorption or on the number of
      periodontal ligament fibroblasts. CONCLUSION: Mechanical stimulation accelerated
      the healing of gingival inflammation by reducing the infiltration of
      polymorphonuclear leukocytes and enhancing fibroblast proliferation and collagen
      synthesis.

PMID- 19602121
TI  - Effect of cyclic mechanical loading on osteoclast recruitment in periodontal
      tissue.
AB  - BACKGROUND AND OBJECTIVE: It is well accepted that cyclic mechanical loading
      induces osteoclastogenesis in periodontal tissue, but its molecular mechanisms
      are not well understood, in part because of a lack of appropriate models. In this
      study, we investigated a novel device that allows cyclic mechanical loading to be
      performed in a well-controlled manner. Furthermore, by employing this model, the
      effect of cyclic loading on osteoclast recruitment in the periodontal tissue was
      described. MATERIAL AND METHODS: By using a newly developed device, the cyclic
      loading of 20 n (reference loading corresponding to the fracture hardness of
      dietary pellets) and two excessive loadings (i.e. 30 and 40 n) were applied to
      maxillary right molars in rats for up to 7 d, and osteoclast recruitment in the
      periodontal tissue was evaluated by analyzing relevant marker proteins using
      immunohistochemistry. RESULTS: Osteoclastogenesis was induced by day 3 within
      alveolar bone subjected to a compression force of 30 n. With both 30 and 40 n
      loadings, cells that were positive to for tartrate-resistant acid phosphate,
      receptor activator of nuclear factor-kappaB ligand and osteoprotegerin were
      significantly increased in the alveolar bone/periodontal ligament in a time
      dependent manner. CONCLUSION: A new device was developed that allows various
      levels of cyclic mechanical loading to be exerted. By using this device in rats,
      early events of osteoclast recruitment in the periodontal tissues were observed
      with excessive loadings in a time-dependent manner, indicating the usefulness of
      this model.

PMID- 19602122
TI  - Regulation of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinases by basic fibroblast growth factor and dexamethasone in
      periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVES: In this study, we investigated the effect of basic
      fibroblast growth factor (bFGF) and dexamethasone (Dex) on mRNA expressions of
      collagen (COL) type I, III and X, matrix metalloproteinases (MMP)-1, -2, -3 and 
      9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2, and also on
      mineralization and morphology of periodontal ligament (PDL) cells. MATERIAL AND
      METHODS: Periodontal ligament cells were obtained from premolar teeth extracted
      for orthodontic reasons. Periodontal ligament cells were cultured with Dulbecco's
      modified Eagle's medium containing: (1) 5% fetal bovine serum (FBS); (2) 5% FBS +
      ascorbic acid (AA, 50 microg/mL); (3) 5% FBS + Dex (10(-7) m) + AA; (4) 5% FBS +
      bFGF (10 ng/mL) + AA; or (5) 5% FBS + Dex (10(-7) m) + bFGF + AA. Cells within
      each group were evaluated for gene expression profile using semi-quantitative
      reverse transcriptase-polymerase chain reaction for COL I, III and X, MMP-1, -2, 
      3 and -9 and TIMP-1 and -2 on days 14 and 21 and for biomineralization by von
      Kossa stain in vitro on day 21. Images of PDL cells were examined using a phase
      contrast microscope. RESULTS: Basic fibroblast growth factor stimulated MMP-1,
      MMP-3 and MMP-9 mRNA expressions and inhibited TIMP-2 mRNA expression. Treatment
      of cells with Dex + bFGF led to downregulation of MMP-1, MMP-3 and MMP-9
      transcripts. Whilst AA alone and Dex alone induced biomineralization of PDL
      cells, bFGF blocked the mineralization activity of the cells. In the Dex + bFGF
      group, more mineral nodules were noted when compared to AA alone and Dex alone
      groups. CONCLUSION: The addition of Dex to culture reversed bFGF-mediated
      inhibition of mineralization. Use of combined bFGF and Dex to regulate PDL cell
      function may be a good therapeutic option to obtain periodontal regeneration.

PMID- 19602123
TI  - Expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and
      extracellular metalloproteinase inducer in human periodontal ligament cells
      stimulated with interleukin-1 beta.
AB  - BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMPs), produced by both
      infiltrating and resident cells of the periodontium, play important roles in
      physiologic and pathologic events. Both interleukin-1 beta and extracellular MMP
      inducer can stimulate the expression of MMPs, which in turn leads to breakdown of
      the periodontium. However, it is currently unknown whether interleukin-1 beta up
      regulates MMPs through stimulating the expression of extracellular MMP inducer.
      The aims of this study were to investigate the effect of interleukin-1 beta on
      the expression of MMP-1, MMP-2 and extracellular MMP inducer in human periodontal
      ligament cells and to evaluate whether the regulation of MMP-1 and MMP-2 by this
      cytokine occurred through an effect on extracellular MMP inducer expression.
      MATERIAL AND METHODS: Cultured human periodontal ligament cells were treated with
      varying concentrations (0.01-10 ng/mL) of interleukin-1 beta at for 6, 12 and 24
      h. Reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent
      assay, gelatin zymography and western blotting were performed to measure the mRNA
      and protein levels of MMP-1, MMP-2 and extracellular MMP inducer. RESULTS: Basal
      levels of mRNA and protein for MMP-1, MMP-2 and extracellular MMP inducer were
      detected in untreated human periodontal ligament cells. Interleukin-1 beta
      significantly up-regulated the expression of MMP-1 and MMP-2 mRNA and protein (p
      < 0.05); however, the levels of mRNA and protein for extracellular MMP inducer
      were not significantly different (p > 0.05). In the culture medium, the
      concentration of MMP-1 was also increased significantly, but the concentration of
      MMP-1 was not related to the concentration of extracellular MMP inducer (R(2) =
      0.2538, p > 0.05). CONCLUSION: Interleukin-1 beta up-regulated the levels of MMP
      1 and MMP-2, but it did not alter the expression of extracellular MMP inducer.
      Expression of MMP-1 and MMP-2 might be elevated by interleukin-1 beta and
      extracellular MMP inducer via two different signal pathways.

PMID- 19602124
TI  - Osteoprotegerin induces osteopontin via syndecan-1 and phosphoinositol 3
      kinase/Akt in human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Our previous study found that thrombin induced
      osteoprotegerin synthesis in human periodontal ligament cells. As elevated levels
      of osteoprotegerin can exert biological effects on various cell types, in the
      present study we investigated the effect of osteoprotegerin on the expression of
      osteopontin in human periodontal ligament cells. MATERIAL AND METHODS: Cultured
      human periodontal ligament cells were treated with recombinant human
      osteoprotegerin (0-100 ng/mL) for 24-48 h. The expression of osteopontin mRNA and
      protein was analyzed using reverse transcription-polymerase chain reaction and
      western blot analyses, respectively. Phosphoinositol 3-kinase inhibitor, Akt
      inhibitor, heparinase, neutralizing antibody against receptor activator of
      nuclear factor-kappaB ligand (RANKL) and syndecan-1, and small interfering RNA
      against syndecan-1, were used to determine the mechanism involved. RESULTS:
      Osteoprotegerin up-regulated the mRNA and protein expression of osteopontin in
      human periodontal ligament cells in a dose-dependent manner. Addition of
      neutralizing antibody against RANKL attenuated the inductive effect of
      osteoprotegerin on osteopontin expression. In addition, the inductive effect of
      osteoprotegerin was abolished by phosphoinositol 3-kinase and Akt inhibitors, as
      well as by syndecan-1 antibody or syndecan-1 small interfering RNA. None of the
      inhibitors had any effect on the background level of osteopontin expression.
      CONCLUSION: An increased level of osteoprotegerin can generate signals via a
      RANKL/syndecan-1/phosphoinositol 3-kinase/Akt pathway. The results also suggest
      that osteopontin is one of the downstream targets of the pathway mediated by
      osteoprotegerin in human periodontal ligament cells. Thus, in addition to
      counteracting RANKL in the RANKL-osteoprotegerin system, osteoprotegerin may play
      a role in periodontal tissue remodeling through modulation of the extracellular
      matrix.

PMID- 19602125
TI  - Up-regulation of osteolytic mediators in human osteosarcoma cells stimulated with
      nicotine.
AB  - BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor in the
      development and further progression of periodontal diseases. However, little is
      known about how nicotine influences the expression of osteolytic mediators in
      cigarette smoking-associated periodontal diseases. The aim of this study was to
      investigate the expression of interleukin-1, interleukin-8, receptor activator of
      nuclear factor-kappaB ligand (RANKL), gelatinases and tissue-type plasminogen
      activator in U2OS cells (from the human osteosarcoma cell line) stimulated with
      nicotine. MATERIAL AND METHODS: Differences in the expression of interleukin-1,
      interleukin-8 and RANKL mRNAs, in response to exposure to various concentrations
      of nicotine (0, 0.125, 0.25, 0.5 and 1 mm) were evaluated in U2OS cells using the
      reverse transcription-polymerase chain reaction.In addition, the levels of
      interleukin-1, interleukin-8 and RANKL proteins were determined using enzyme
      linked immunosorbent assays. The gelatinolytic and caseinolytic activities in
      nicotine treated-U2OS cells were demonstrated using gelatin and casein
      zymography, respectively. RESULTS: Nicotine was found to increase the expression
      of interleukin-1, interleukin-8 and RANKL mRNA and protein in U2OS cells (p <
      0.05). The gelatin zymograms revealed that matrix metalloproteinase (MMP)-2 and
      MMP-9 were secreted by U2OS cells. The secretion of MMP-2 and MMP-9 occurred in a
      dose-dependent manner that was dependent on the concentration of nicotine (p <
      0.05). Casein zymography exhibited a caseinolytic band with a molecular weight of
      70 kDa, indicative of the presence of tissue-type plasminogen activator. Tissue
      type plasminogen activator was also found to be up-regulated by nicotine in a
      dose-dependent manner (p < 0.05). CONCLUSION: Taken together, the results of the
      present study indicated that smoking modulation of bone destruction in
      periodontal disease may involve various osteolytic mediators, such as interleukin
      1, interleukin-8, RANKL, MMP-2, MMP-9, and tissue-type plasminogen activator.

PMID- 19602126
TI  - The antibacterial effect of photodynamic therapy in dental plaque-derived
      biofilms.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy has been advocated as an
      alternative to antimicrobial agents to suppress subgingival species and to treat
      periodontitis. Bacteria located within dense biofilms, such as those encountered
      in dental plaque, have been found to be relatively resistant to antimicrobial
      therapy. In the present study, we investigated the ability of photodynamic
      therapy to reduce the number of bacteria in biofilms by comparing the
      photodynamic effects of methylene blue on human dental plaque microorganisms in
      the planktonic phase and in biofilms. MATERIAL AND METHODS: Dental plaque samples
      were obtained from 10 subjects with chronic periodontitis. Suspensions of plaque
      microorganisms from five subjects were sensitized with methylene blue (25
      microg/mL) for 5 min then exposed to red light. Multispecies microbial biofilms
      developed from the same plaque samples were also exposed to methylene blue (25
      microg/mL) and the same light conditions as their planktonic counterparts. In a
      second set of experiments, biofilms were developed with plaque bacteria from five
      subjects, sensitized with 25 or 50 microg/mL of methylene blue and then exposed
      to red light. After photodynamic therapy, survival fractions were calculated by
      counting the number of colony-forming units. RESULTS: Photodynamic therapy killed
      approximately 63% of bacteria present in suspension. By contrast, in biofilms,
      photodynamic therapy had much less of an effect on the viability of bacteria (32%
      maximal killing). CONCLUSION: Oral bacteria in biofilms are affected less by
      photodynamic therapy than bacteria in the planktonic phase. The antibacterial
      effect of photodynamic therapy is reduced in biofilm bacteria but not to the same
      degree as has been reported for treatment with antibiotics under similar
      conditions.

PMID- 19602130
TI  - Risk stratification and outcomes in hemodynamically stable patients with acute
      pulmonary embolism: a prospective multicenter, cohort study: a rebuttal.

PMID- 19602127
TI  - Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1
      cells via the mitochondrial pathway.
AB  - BACKGROUND AND OBJECTIVE: We reported previously that cyclosporine A induces a
      high level of expression of p21 in rat gingival keratinocytes and in OECM1 cells.
      In this study, the apoptosis of gingival keratinocytes after treatment with
      cyclosporine A was evaluated using the same models. MATERIAL AND METHODS: Forty
      Sprague-Dawley rats with right edentulous ridges were assigned into cyclosporine
      A (30 mg/kg) and control groups. Four weeks later, gingivae were screened for
      expression of apoptotic genes using microarray analyses and DNA fragmentation.
      The expression of bcl2-associated X protein (Bax), apoptosis-inducing factor
      (AIF) and Caspase 3 mRNAs, and the expression of Bax, AIF, Caspase 9 and Fas
      proteins, were analyzed using the reverse transcription-polymerase chain reaction
      and immunohistochemistry, respectively. Apoptosis in OECM1 cells (keratinocytes
      of a gingival carcinoma cell line), after treatment with cyclosporine A, was
      evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry,
      whereas the expression of Bax, AIF, Caspase 3 and 8, Bcl-2 and Fas proteins were
      examined using western blotting. RESULTS: According to microarray analyses, the
      expression of certain apoptotic genes was altered in the gingiva of rats who
      received cyclosporine A, and increased number of DNA fragments were detected.
      Expression of mRNA or protein for Bax, AIF and Caspase 3 and 9 in the gingivae of
      rats increased after treatment with cyclosporine A. An increased number of
      apoptotic bodies and of OECM1 cells in the sub-G1 phase was observed after
      treatment with cyclosporine A. Increased expression of AIF, Bax and Caspase 3
      protein, but not of bcl-2, Caspase 8 or Fas protein, was observed in cells after
      treatment with cyclosporine A. CONCLUSION: Based on the above findings, we
      suggest that cyclosporine A might enhance the apoptosis of gingival
      keratinocytes, mainly via the mitochondrial pathway.

PMID- 19602131
TI  - NSAIDs discontinuation and myocardial infarction.

PMID- 19602132
TI  - Liver fat and lipid oxidation in humans.
AB  - BACKGROUND: Studies in animals show that changes in hepatic fatty acid oxidation
      alter liver fat content. Human data regarding whole-body and hepatic lipid
      oxidation are controversial and based on studies of only a few subjects. AIMS: We
      examined whether whole-body and hepatic lipid oxidation are altered in subjects
      with non-alcoholic fatty liver disease (NAFLD) compared with controls. METHODS:
      In vivo measurements of rates of substrate oxidation and insulin sensitivity
      (using the euglycaemic hyperinsulinaemic clamp technique in combination with
      indirect calorimetry and infusion of [3-(3)H]glucose) were performed in subjects
      with NAFLD [mean liver fat 14.0% (interquartile range 7.5-20.5%), n=29] and in
      control subjects [1.6% (1.0-3.0%), n=29]. Liver fat was measured using proton
      magnetic resonance spectroscopy. Plasma concentrations of 3-hydroxybutyrate (3
      OHB) were measured as markers of hepatic lipid oxidation. RESULTS: In the basal
      state, substrate oxidation rates and serum 3-OHB concentrations were comparable
      in subjects with and without NAFLD. Plasma 3-OHB concentrations were similarly
      suppressed by insulin in both the groups. During the insulin infusion, whole-body
      lipid oxidation was inversely correlated with insulin-stimulated glucose disposal
      (r=-0.48, P<0.0001), which was lower in subjects with NAFLD [3.7+/-0.2 mg/(kg fat
      free mass min)] than in the control subjects [5.0+/-0.3 mg/(kg fat-free mass
      min), P=0.0008]. CONCLUSIONS: Hepatic lipid oxidation is unchanged in NAFLD.
      Whole-body lipid oxidation is increased because of peripheral insulin resistance.
      These data imply that alterations in hepatic fatty acid oxidation do not
      contribute to liver fat content in humans.

PMID- 19602133
TI  - Prevalence of cryoglobulinaemia in hepatitis C virus- and hepatitis C virus/human
      immunodeficiency virus-infected individuals: implications for renal function.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) and human immunodeficiency virus
      (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production
      of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis
      and renal failure. The presence of cryoglobulins was investigated in the sera of
      HCV-monoinfected and HCV/HIV-coinfected individuals. Associations between types
      of cryoglobulins and HCV genotypes, viral load and renal function tests were also
      evaluated. PATIENTS AND METHODS: Seventy-seven patients were enrolled in this
      study. Forty-four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins
      were detected in the sera by electrophoresis and immunofixation. Serum urea and
      creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C
      concentration (CC) were analysed to evaluate renal function. The control group
      included 16 healthy individuals. RESULTS: The occurrence of cryoglobulinaemia in
      HCV-monoinfected patients was 55%, whereas in HCV/HIV-coinfected patients it was
      64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in
      25%. The prevalence of cryoglobulinaemia was significantly higher in infection
      with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P<0.01). The most frequently
      occurring heavy chains were gamma-type (96%). Light chains, the kappa-type, were
      detected in all patients. The CC concentration was significantly higher in
      HCV/HIV-coinfected patients compared with controls (718 vs. 392 ng/ml; P<0.005)
      or HCV-monoinfected patients (508 ng/ml; P<0.007). There was correlation between
      the serum CC concentration and the incidence of cryoglobulinaemia (R=0.44;
      P<0.00015), which was particularly evident in HCV monoinfection (R=0.43;
      P<0.0034). CONCLUSIONS: Genotype-1 infection is an important risk factor for
      cryoglobulinaemia. Standard renal function tests are not sufficient for the
      prediction of renal failure in HCV-infected patients. Serum CC concentration
      allows to establish an early diagnosis of renal insufficiency related to
      cryoglobulinaemia.

PMID- 19602134
TI  - Analysis of the efficacy of treatment with peginterferon alpha-2a and ribavirin
      in patients coinfected with hepatitis B virus and hepatitis C virus.
AB  - OBJECTIVE: To study the virological features of patients coinfected with
      hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of
      combination therapy with peginterferon alpha-2a and ribavirin in these patients.
      METHODS: The epidemiological and virological data of 50 patients coinfected with
      HBV and HCV were analysed. The virological response rates of patients treated
      with peginterferon alpha-2a and ribavirin between the HBV and HCV coinfection
      group and the HCV monoinfection group were compared. RESULTS: HCV-dominant virus
      strains accounted for 92.0% of the 50 coinfected individuals, and HCV- and HBV
      dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the
      patients coinfected with HBV and HCV was 4.6+/-0.9 log(10) copies/ml, which was
      significantly lower than that in the HBV monoinfection group (5.9+/-1.2 log(10)
      copies/ml) (t=5.964, P<0.01). The HBeAg-positive rate (12.0%, 6/50) of the
      coinfection group was significantly lower than (45.3%, 19/42) that of the HBV
      monoinfection group (chi(2)=12.743, P<0.01). The partial early virological
      response (pEVR) rate and the end-of-treatment virological response (ETVR) rate
      (50.0%, 15/30; 90.0%, 27/30) of patients with genotype 1 in the coinfection group
      were significantly higher than those (16.0%, 4/25; 56.0%, 14/25) in the HCV
      monoinfection group (chi(2)=6.971, P=0.008; chi(2)=8.307, P=0.004). The relapse
      rate (55.6%, 15/27) of patients with genotype 1 in the coinfection group was
      significantly higher than that (21.4%, 3/14) in the HCV monoinfection group
      (chi(2)=4.360, P=0.037). The sustained virological response (SVR) rate (40.0%,
      12/30) of patients with genotype 1 in the coinfection group was compared with
      that of the HCV monoinfection group (44.0%, 11/25) (chi(2)=0.090, P=0.765). There
      was no significant difference in the on-treatment virological response, ETVR, SVR
      and relapse rates between two groups for patients with genotype 2. The incidence
      of side effects (30%, 15/50) of patients in the coinfection group was
      significantly higher than that (13%, 6/46) in the HCV monoinfection group
      (chi(2)=4.031, P=0.045). The reactivation rate of HBV DNA (33.3%, 9/27) with HCV
      SVR was significantly higher than that of patients without SVR (8.7%, 2/23)
      (chi(2)=4.393, P=0.036). CONCLUSIONS: The replication of HBV was suppressed, and
      HCV was the dominant virus strain. Compared with HCV-monoinfected patients, pEVR,
      ETVR and relapse rates of patients with genotype 1 in the coinfection group were
      high, while they shared similar SVR rates. HBV and HCV coinfection had no impact
      on the rate of virological response for genotype 2.

PMID- 19602135
TI  - Microvascular optical assessment confirms the presence of peripheral autonomic
      dysfunction in primary biliary cirrhosis.
AB  - BACKGROUND: Autonomic dysfunction (AD) is a significant problem in primary
      biliary cirrhosis (PBC) and is equally present in early disease stages.
      Currently, AD in PBC is considered to be central in origin. The aim of this study
      was to examine peripheral mechanisms in the pathogenesis of AD in PBC using novel
      microvascular optical assessments for this patient group. METHODS: Twenty-four
      early stage PBC patients and 24 age-matched controls attended for two
      microvascular optical-based measurement techniques. Firstly, the regulation of
      microvascular blood volume to the periphery was assessed using multisite
      photoplethysmography (PPG) by examining the degree of correlation between the
      right and left sides of the body, with reduced correlation consistent with
      peripheral AD. Secondly, the peripheral vasomotor reflex response to standing was
      dynamically tested using laser Doppler flowmetry to quantify the degree of
      autonomic tone in peripheral vasoconstriction. RESULTS: PBC patients had a
      significantly reduced right to left side blood volume multisite PPG correlation
      compared with controls when corrected for age, body mass index, heart rate and
      systolic blood pressure [impaired synchronization between pulse wave amplitude
      between right and left fingers and right and left ears (both P<0.05)]. The veno
      arteriolar reflex on standing in PBC patients was significantly lower than for
      the controls, consistent with poorer autonomic tone for vasoconstriction in PBC
      (P<0.01). CONCLUSIONS: This study provides evidence for the presence of
      peripheral autonomic nervous system involvement in PBC. Prospective studies are
      now warranted to determine the full clinical potential of microvascular optical
      assessment in PBC.

PMID- 19602136
TI  - Protein-calorie malnutrition as a prognostic indicator of mortality among
      patients hospitalized with cirrhosis and portal hypertension.
AB  - BACKGROUND: We conducted a nationwide analysis of the prevalence of protein
      calorie malnutrition (PCM) in patients with cirrhosis and portal hypertension
      (PHTN) and to determine its mortality and economic impact. METHODS: We used the
      Nationwide Inpatient Sample (NIS) to identify admissions throughout the US with
      cirrhosis and PHTN between 1998 and 2005 using the International Classification
      of Diseases, 9th Revision diagnostic codes. Prevalence of PCM in this group of
      patients with cirrhosis was compared with that of general medical inpatients. The
      impact of PCM on in-hospital mortality was quantified using multiple logistic
      regression analysis. RESULTS: There were 114 703 admissions with cirrhosis and
      PHTN in the NIS between 1998 and 2005. The prevalence of PCM was substantially
      higher among patients with cirrhosis and PHTN compared with general medical
      inpatients (6.1 vs. 1.9%, P<0.0001), with an adjusted odds ratio of 1.55 (95% CI:
      1.4-1.7). There was greater prevalence of ascites (64.6 vs. 47.8%, P<0.0001) and
      hepatorenal syndrome (5.1 vs. 2.8%, P<0.0001) among those with PCM and cirrhosis.
      In-hospital mortality was two-fold higher among patients with cirrhosis and PCM
      (14.1 vs. 7.5%, P<0.0001), with an adjusted mortality of 1.76 (95% CI: 1.59
      1.94). PCM was associated with greater length of stay (8.7 vs. 5.7 days,
      P<0.0001) and hospital charges (US$36 818 vs. US$22 673; P<0.0001) among patients
      with cirrhosis. CONCLUSIONS: PCM is more common among patients with cirrhosis and
      PHTN than the general medical population, and is associated with higher in
      hospital mortality and resource utilization. PCM may be an indicator of greater
      disease severity and should be routinely assessed on admission.

PMID- 19602137
TI  - Chronic hepatitis C virus infection associated with autonomic dysfunction.
AB  - BACKGROUND: Impaired autonomic function has been described in patients with
      chronic liver diseases from different aetiologies, and has proven to be a poor
      prognostic indicator. To date, it is not known how chronic hepatitis C virus
      (HCV) infection affects the autonomic nervous system. AIMS: In the present study,
      we compared cardiovagal autonomic function in patients with chronic HCV infection
      and healthy controls and examined the relation between autonomic function and
      serum levels of aminotransferases, HCV RNA, cryoglobulins, albumin and glucose.
      METHODS: Autonomic function was assessed in 45 treatment-naive patients with
      chronic HCV infection and in 40 healthy controls by determining spontaneous
      baroreflex sensitivity (BRS) and heart rate variability (HRV) indices. The R-R
      interval was determined by electrocardiogram recording; continuous radial artery
      pressure was monitored simultaneously by applanation tonometry. Laboratory
      analyses and quantitative polymerase chain reaction for serum HCV RNA level were
      performed by standard procedures. RESULTS: BRS and HRV time and frequency domain
      indices were lower in patients with HCV infection compared with healthy controls
      [7.1+/-3.4 vs. 11.5+/-6.5 ms/mmHg for BRS, 168.5+/-160.9 vs. 370.7+/-349.4 ms(2)
      for low-frequency HRV (mean+/-SD); P<0.01]. Multivariate analysis showed that
      autonomic dysfunction in HCV-infected patients correlated with elevated alanine
      aminotransferase levels, but was not associated with serum HCV RNA levels and
      cryoglobulins. CONCLUSION: Our results suggest that impaired autonomic function
      is caused by chronic HCV infection. Further studies are needed, however, to
      identify the underlying mechanisms.

PMID- 19602138
TI  - Identification of bacterial DNA in neutrocytic and non-neutrocytic cirrhotic
      ascites by means of a multiplex polymerase chain reaction.
AB  - BACKGROUND: Even though bacterial cultures of ascitic fluid are negative in up to
      65% of the cases of spontaneous bacterial peritonitis (SBP); bacterial DNA
      (bactDNA) has been frequently detected in episodes of SBP as well as in culture
      negative non-neutrocytic ascites. AIMS: To evaluate multiplex polymerase chain
      reaction (PCR) for pathogen identification in SBP and to determine the prevalence
      of ascitic bactDNA and its prognostic relevance in hospitalized patients with
      liver cirrhosis. METHODS: Ascitic fluid from 68 consecutive patients who
      underwent diagnostic paracentesis was analysed for polymorphonuclear leucocyte
      (PMN) count, bacterial culture and bactDNA. BactDNA was identified by gel
      analysis after multiplex PCR of selectively enriched prokaryotic nucleic acids.
      Correlations of bactDNA status with PMN count, bacterial culture result and 3
      month mortality were determined for neutrocytic and for non-neutrocytic ascites.
      RESULTS: 11/68 patients presented with an elevated ascitic PMN count. BactDNA was
      detected in 5/5 culture-positive neutrocytic samples, in 1/6 culture-negative
      neutrocytic samples and in 8/56 culture-negative non-neutrocytic samples. Three
      month mortality did not differ with respect to ascitic bactDNA status (7/14 vs.
      14/47, P=0.162). 3-month mortality was increased in the presence of ascitic
      bactDNA for patients older than 65 years (4/5 vs. 4/14, P=0.046) and for patients
      with a model for end-stage liver disease score >15 (7/10 vs. 9/30, P=0.025).
      CONCLUSIONS: Identification of ascitic bactDNA is an appropriate alternative to
      bacterial ascite culture for pathogen identification in patients at risk for SBP.
      Its prognostic relevance as a proposed marker of bacterial translocation for
      certain risk groups has to be further evaluated.

PMID- 19602139
TI  - Evaluating the risk of hepatitis B reactivation in patients with haematological
      malignancies: is the serum hepatitis B virus profile reliable?
AB  - BACKGROUND/AIM: Patients with an occult hepatitis B virus (HBV) infection
      undergoing deep immunosuppression are potentially at risk of HBV reactivation. In
      order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in
      serum could be used to predict the reactivation of an occult HBV infection, we
      performed a retrospective study in a cohort of Sicilian patients with
      oncohaematological diseases. METHODS: We studied by a highly sensitive ad hoc
      nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients
      requiring chemotherapy. RESULTS: Thirty-three patients (44%) were HBV
      seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV
      seropositive (anti-HBc and/or anti-HBs positive). Baseline serum HBV DNA was
      positive in nine out of 33 HBV-seronegative patients and in nine out of 42 HBV
      seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed
      in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs.
      14%, P=0.9), and in five out of 18 HBV DNA-positive vs. six out of 57 HBV DNA
      negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found
      in 18 patients (24.3%), although with no correlation to HBV serological status,
      presence of serum HBV DNA or frequency of HBsAg seroconversion. CONCLUSIONS: In
      oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV
      DNA testing at baseline has a 28% predictive ability to forecast HBsAg
      seroconversion in HBV DNA-positive patients, and a 90% ability to forecast
      persistent HBsAg negativity in HBV DNA-negative patients, a better performance
      than serological tests.

PMID- 19602140
TI  - Teucrium polium in prevention of steatohepatitis in rats.
AB  - BACKGROUND: In this study, we tried to evaluate whether the ethyl acetate (EtOAc)
      extract of Teucrium polium, with a high antioxidant activity, is able to prevent
      the incidence of nonalcoholic steatohepatitis. METHODS: Nonalcoholic
      steatohepatitis was induced in male N-Mary rats using a methionine/choline
      deficient (MCD) diet. Rats were given normal diet (A), normal diet+EtOAc extract
      (B), MCD diet (C) and MCD diet+EtOAc (D). RESULTS: The MCD diet led to grade 1
      liver steatosis, inflammation and ballooning degeneration. In group D, these
      factors abated to grade 0 in 80% of the rats. In groups receiving the EtOAc
      extract, lipoprotein profiles had significantly improved relative to those not
      receiving the extract. Also, a dramatic reduction was observed in the sera
      alkaline phosphatase, aspartate aminotransferase and alanine aminoteransferase
      activities. The activities of the liver superoxide dismutase, glutathione
      peroxidase and glutathione reductase enzymes were also enhanced. CONCLUSION: The
      EtOAc extract could reverse the adverse effects of the MCD diet.

PMID- 19602142
TI  - Modeling the effect of facial topographies upon the visual field of humans and
      primates.
AB  - PURPOSE: To establish a virtual device that can predict the effect of facial
      features on the visual field of humans and primates. METHODS: Virtual masks were
      obtained from human subjects, and macaque, chimpanzee and baboon taxidermic
      specimens, and aligned with upright head orientation at the center of a virtual
      perimeter-like dome (radius = 50 m) developed with Cinema 4D. Virtual
      searchlights positioned at the masks' pupils were then allowed to 'paint' facial
      elements obstructing their path, and demarcate the unobstructed rays at the
      perimetric surface and on a virtual ground floor related to eye level.
      Searchlight positions along the human mask's pupillary axis were identified by
      maximum congruence to Goldmann visual field limits. RESULTS: The human contours
      largely concur with large-stimulus isopters displaying the limiting role of the
      nasal ridge, and the relatively extended ventral and temporal limits. In
      contrast, the facial design of chimpanzees and baboons obstructs significant
      portions of the ventral foreground (>2 m cf < 0.5 m in human), while there appear
      to be larger binocular overlaps (125 degrees in chimp cf 90 degrees in human).
      CONCLUSIONS: The model provides information on anatomical constraints for
      monocular and binocular visual field extensions including projection of the
      ventral field on a virtual floor.

PMID- 19602141
TI  - Identification of amino acid residues of the pheromone-binding domain of the
      transcription factor TraR that are required for positive control.
AB  - Genes required for replication and for conjugal transfer of the Agrobacterium
      tumefaciens Ti plasmid are regulated by the quorum sensing transcription factor
      TraR, whose N-terminal domain binds to the pheromone 3-oxo-octanoylhomoserine
      lactone (OOHL) and whose C-terminal domain binds to specific DNA sequences called
      tra boxes. Here, we constructed 117 mutants, altering 103 surface-exposed amino
      acid residues of the TraR N-terminal domain. Each mutant was tested for
      activation of the traI promoter, where TraR binds to a site centred 45
      nucleotides upstream of the transcription start site, and of the traM promoter,
      where TraR binds a site centred 66 nucleotides upstream. Alteration of 18
      residues blocked activity at the traI promoter. Of these, alteration at three
      positions impaired TraR abundance or DNA binding, leaving 15 residues that are
      specifically needed for positive control. Of these 15 residues, nine also blocked
      or reduced activity at the traM promoter, while six had no effect. Amino acid
      residues required for activation of both promoters probably contact the C
      terminal domain of the RNA polymerase alpha subunit, while residues required only
      for traI promoter activation may contact another RNA polymerase component.

PMID- 19602143
TI  - Clinical outcomes of corneal wavefront customized ablation strategies with
      SCHWIND CAM in LASIK treatments.
AB  - PURPOSE: To evaluate the clinical outcomes of aspheric corneal wavefront (CW)
      ablation profiles in LASIK treatments. METHODS: Thirty eyes treated with CW
      ablation profiles were included after a follow-up of 6 months. In all cases,
      standard examinations including preoperative and postoperative wavefront analysis
      with a CW topographer (Optikon Keratron Scout) were performed. Custom Ablation
      Manager (CAM) software was used to plan corneal wavefront customized aspheric
      treatments, and the ESIRIS flying spot excimer laser system was used to perform
      the ablations (both SCHWIND eye-tech-solutions, Kleinhostheim, Germany). Clinical
      outcomes were evaluated in terms of predictability, refractive outcome, safety,
      and wavefront aberration. RESULTS: In general, the postoperative uncorrected
      visual acuity and the best corrected visual acuity improved (p < 0.001). In
      particular, the trefoil, coma, and spherical aberrations, as well as the total
      root-mean-square values of higher order aberrations, were significantly reduced
      (p < 0.05) when the pre-existing aberrations were greater than the repeatability
      and the biological noise. CONCLUSIONS: The study results indicate that the
      aspheric corneal wavefront customized CAM approach for planning ablation volumes
      yields visual, optical, and refractive results comparable to those of other
      wavefront-guided customized techniques for correction of myopia and myopic
      astigmatism. The CW customized approach shows its strength in cases where
      abnormal optical systems are expected. Apart from the risk of additional ablation
      of corneal tissue, systematic wavefront-customized corneal ablation can be
      considered as a safe and beneficial method.

PMID- 19602144
TI  - The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts
      exclusively through its control over the transcription of the RsmY and RsmZ
      regulatory small RNAs.
AB  - We report here the results of an analysis of the regulatory range of the
      GacS/GacA two-component system in Pseudomonas aeruginosa. Using microarrays, we
      identified a large number of genes that are regulated by the system, and detected
      a near complete overlap of these genes with those regulated by two small RNAs
      (sRNAs), RsmY and RsmZ, suggesting that the expression of all GacA-regulated
      genes is RsmY/Z-dependent. Using genome-wide DNA-protein interaction analyses, we
      identified only two genomic regions that associated specifically with GacA,
      located upstream of the rsmY and rsmZ genes. These results demonstrate that in P.
      aeruginosa, the GacS/GacA system transduces the regulatory signals to downstream
      genes exclusively by directly controlling the expression of only two genes rsmY
      and rsmZ. These two sRNAs serve as intermediates between the input signals and
      the output at the level of mRNA stability, although additional regulatory inputs
      can influence the levels of these two riboregulators. We show that the A+T-rich
      DNA segment upstream of rsmZ is bound and silenced by MvaT and MvaU, the global
      gene regulators of the H-NS family. This work highlights the importance of post
      transcriptional mechanisms involving sRNAs in controlling gene expression during
      bacterial adaptation to different environments.

PMID- 19602145
TI  - Sinorhizobium meliloti CpdR1 is critical for co-ordinating cell cycle progression
      and the symbiotic chronic infection.
AB  - ATP-driven proteolysis plays a major role in regulating the bacterial cell cycle,
      development and stress responses. In the nitro -fixing symbiosis with host
      plants, Sinorhizobium meliloti undergoes a profound cellular differentiation,
      including endoreduplication of the ome. The regulatory mechanisms governing the
      alterations of the S. meliloti cell cycle in planta are largely unknown. Here, we
      report the characterization of two cpdR homologues, cpdR1 and cpdR2, of S.
      meliloti that encode single-domain response regulators. In Caulobacter
      crescentus, CpdR controls the polar localization of the ClpXP protease, thereby
      mediating the regulated proteolysis of key protein(s), such as CtrA, involved in
      cell cycle progression. The S. meliloti cpdR1-null mutant can invade the host
      cytoplasm, however, the intracellular bacteria are unable to differentiate into
      bacteroids. We show that S. meliloti CpdR1 has a polar localization pattern and a
      role in ClpX positioning similar to C. crescentus CpdR, suggesting a conserved
      function of CpdR proteins among alpha-proteobacteria. However, in S. meliloti,
      free-living cells of the cpdR1-null mutant show a striking morphology of
      irregular coccoids and aberrant DNA replication. Thus, we demonstrate that CpdR1
      mediates the co-ordination of cell cycle events, which are critical for both the
      free-living cell division and the differentiation required for the chronic
      intracellular infection.

PMID- 19602146
TI  - Characterization of starvation-induced dispersion in Pseudomonas putida biofilms:
      genetic elements and molecular mechanisms.
AB  - Pseudomonas putida OUS82 biofilm dispersal was previously shown to be dependent
      on the gene PP0164 (here designated lapG). Sequence and structural analysis has
      suggested that the LapG geneproduct belongs to a family of cysteine proteinases
      that function in the modification of bacterial surface proteins. We provide
      evidence that LapG is involved in P. putida OUS82 biofilm dispersal through
      modification of the outer membrane-associated protein LapA. While the P. putida
      lapG mutant formed more biofilm than the wild-type, P. putida lapA and P. putida
      lapAG mutants displayed decreased surface adhesion and were deficient in
      subsequent biofilm formation, suggesting that LapG affects LapA, and that the
      LapA protein functions both as a surface adhesin and as a biofilm matrix
      component. Lowering of the intracellular c-di-GMP level via induction of an EAL
      domain protein led to dispersal of P. putida wild-type biofilm but did not
      disperse P. putida lapG biofilm, indicating that LapG exerts its activity on LapA
      in response to a decrease in the intracellular c-di-GMP level. In addition,
      evidence is provided that associated to LapA a cellulase-degradable
      exopolysaccharide is part of the P. putida biofilm matrix.

PMID- 19602147
TI  - CzcP is a novel efflux system contributing to transition metal resistance in
      Cupriavidus metallidurans CH34.
AB  - Cupriavidus metallidurans CH34 possesses a multitude of metal efflux systems.
      Here, the function of the novel P(IB4)-type ATPase CzcP is characterized, which
      belongs to the plasmid pMOL30-mediated cobalt-zinc-cadmium (Czc) resistance
      system. Contribution of CzcP to transition metal resistance in C. metallidurans
      was compared with that of three P(IB2)-type ATPases (CadA, ZntA, PrbA) and to
      other efflux proteins by construction and characterization of multiple deletion
      mutants. These data also yielded additional evidence for an export of metal
      cations from the periplasm to the outside of the cell rather than from the
      cytoplasm to the outside. Moreover, metal-sensitive Escherichia coli strains were
      functionally substituted in trans with CzcP and the three P(IB2)-type ATPases.
      Metal transport kinetics performed with inside-out vesicles identified the main
      substrates for these four exporters, the K(m) values and apparent turn-over
      numbers. In combination with the mutant data, transport kinetics indicated that
      CzcP functions as 'resistance enhancer': this P(IB4)-type ATPase exports
      transition metals Zn(2+), Cd(2+) and Co(2+) much more rapidly than the three
      P(IB2)-type proteins. However, a basic resistance level has to be provided by the
      P(IB2)-type efflux pumps because CzcP may not be able to reach all different
      speciations of these metals in the cytoplasm.

PMID- 19602148
TI  - Host legume-exuded antimetabolites optimize the symbiotic rhizosphere.
AB  - Rhizobia form symbiotic nodules on host legumes and fix nitrogen for their hosts
      in exchange for nutrients. In order to establish this mutually beneficial
      relationship, rhizobia must compete with other soil bacteria in the host legume
      rhizosphere to colonize plant roots efficiently. A promoter-trap transposon
      screen in Mesorhizobium tianshanense, a Rhizobium that forms nodules on licorice
      (Glycyrrhiza uralensis) plants revealed that the expression of msiA, which
      encodes a putative exporter protein belonging to the LysE family of
      translocators, is activated by both legume exudates and MsiR, a LysR family
      transcriptional regulator. Chemical analysis suggests that the msiA-inducing
      signal in exudates is canavanine, an anti-metabolite present in the seeds and
      exudates of a variety of legume plants. We show that MsiA serves as a canavanine
      exporter that is indispensable for canavanine resistance in M. tianshanense. We
      also show that the expression of MsiA homologues in other rhizobial species is
      induced by canavanine and is critical for canavanine resistance. Furthermore,
      rhizobial canavanine resistance is important for root hair adherence as well as
      for survival in a canavanine-producing legume rhizosphere. Together, these data
      suggest that host legumes may exude specific antimetabolites into their
      surroundings to optimize the bacterial population in order to have successful
      symbiotic events with rhizobia.

PMID- 19602149
TI  - Direct stimulus perception and transcription activation by a membrane-bound DNA
      binding protein.
AB  - Few membrane proteins with a role in transcriptional regulation have been
      studied, and none are able to perceive their respective stimuli and activate
      transcription of their regulons without the aid of auxiliary proteins. The
      bacitracin resistance regulator, BcrR, of Enterococcus faecalis is a membrane
      bound DNA binding protein and is required for bacitracin-dependent expression of
      the bacitracin resistance genes, bcrABD. Here, we show that BcrR interacts
      directly with Zn2+ bacitracin (Kd = 2-5 micropM), but not metal-free bacitracin.
      A solution-based DNA binding assay demonstrated that the affinity of BcrR for its
      target DNA is much higher (Kd = 40 nM) than previously found for transmembrane
      regulators and is comparable to that of soluble DNA binding proteins. A construct
      of BcrR that lacked the transmembrane domain was unable to bind to DNA,
      indicating that membrane localization was important for DNA binding. Bacitracin
      did not cause a change in the DNaseI footprint of BcrR on the bcrA promoter, but
      in vitro transcription assays with BcrR proteoliposomes showed bacitracin
      dependent activation of transcription. These findings demonstrate that BcrR is a
      bona fide one-component transmembrane signal transduction system, which perceives
      an extracellular stimulus (presence of bacitracin) and relays it to an
      intracellular transcriptional response independent of any auxiliary proteins.

PMID- 19602150
TI  - Dynamics of cell wall components of Magnaporthe grisea during infectious
      structure development.
AB  - Oligosaccharides derived from cell wall of fungal pathogens induce host primary
      immune responses. To understand fungal strategies circumventing the host plant
      immune responses, cell wall polysaccharide localization was investigated using
      fluorescent labels during infectious structure differentiation in the rice blast
      fungus Magnaporthe grisea. alpha-1,3-glucan was labelled only on appressoria
      developing on plastic surfaces, whereas it was detected on both germ tubes and
      appressoria on plant surfaces. Chitin, chitosan and beta-1,3-glucan were detected
      on germ tubes and appressoria regardless of the substrate. Major polysaccharides
      labelled at accessible surface of infectious hyphae were alpha-1,3-glucan and
      chitosan, but after enzymatic digestion of alpha-1,3-glucan, beta-1,3-glucan and
      chitin became detectable. Immunoelectron microscopic analysis showed alpha-1,3
      glucan and beta-1,3-glucan intermixed in the cell wall of infectious hyphae;
      however, alpha-1,3-glucan tended to be distributed farther from the fungal cell
      membrane. The fungal cell wall became more tolerant to chitinase digestion upon
      accumulation of alpha-1,3-glucan. Accumulation of alpha-1,3-glucan was dependent
      on the Mps1 MAP kinase pathway, which was activated by a plant wax derivative,
      1,16-hexadecanediol. Taken together, alpha-1,3-glucan spatially and functionally
      masks beta-1,3-glucan and chitin in the cell wall of infectious hyphae. Thus, a
      dynamic change of composition of cell wall polysaccharides occurs during plant
      infection in M. grisea.

PMID- 19602151
TI  - Mycobacterial PE, PPE and ESX clusters: novel insights into the secretion of
      these most unusual protein families.
AB  - The human pathogen Mycobacterium tuberculosis harbours a large number of genes
      that encode proteins whose N-termini contain the characteristic motifs Pro-Glu
      (PE) or Pro-Pro-Glu (PPE). A subgroup of the PE proteins contains polymorphic GC
      rich sequences (PGRS), while a subgroup of the PPE proteins contains major
      polymorphic tandem repeats (MPTR). The function of most of these proteins remains
      unknown. However, in this issue of Molecular Microbiology, Abdallah and
      colleagues show that PE_PGRS proteins from the model organism Mycobacterium
      marinum are secreted by components of the ESX-5 system that belongs to the
      recently defined type VII secretion systems. These observations, which now need
      to be addressed and confirmed in M. tuberculosis, open new perspectives on the
      function of these highly abundant proteins.

PMID- 19602152
TI  - PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type
      VII secretion system ESX-5.
AB  - ESX-5 is one of the five type VII secretion systems found in mycobacteria. These
      secretion systems are also known as ESAT-6-like secretion systems. Here, we have
      determined the secretome of ESX-5 by a proteomic approach in two different
      strains of Mycobacterium marinum. Comparison of the secretion profile of wild
      type strains and their ESX-5 mutants showed that a number of PE_PGRS and PPE-MPTR
      proteins are dependent on ESX-5 for transport. The PE and PPE protein families
      are unique to mycobacteria, are highly expanded in several pathogenic species,
      such as Mycobacterium tuberculosis and M. marinum, and certain family members are
      cell surface antigens associated with virulence. Using a monoclonal antibody
      directed against the PGRS domain we showed that nearly all PE_PGRS proteins that
      are recognized by this antibody are missing in the supernatant of ESX-5 mutants.
      In addition to PE_PGRS and PPE proteins, the ESX-5 secretion system is
      responsible for the secretion of a ESAT-6-like proteins. Together, these data
      show that ESX-5 is probably a major secretion pathway for mycobacteria and that
      this system is responsible for the secretion of recently evolved PE_PGRS and PPE
      proteins.

PMID- 19602156
TI  - Preparticipation screening and preparticipation forms.
AB  - Published literature supports the fact that many pediatric patients at risk for
      sudden cardiac death (SCD) will exhibit warning signs and symptoms. The use of
      comprehensive cardiovascular screening questionnaires and physical examination
      should help identify these patients at risk. Recognizing that many of the cardiac
      disorders predisposing to SCD are genetic, the role of careful and extensive
      family history cannot be overemphasized. While preparticipation screening is
      primarily directed toward high school and college athletes, the use of
      cardiovascular screening should also be considered for children of all ages.

PMID- 19602154
TI  - Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h)
      intravenous insulin infusion for the initial treatment of diabetic ketoacidosis
      in children with type 1 diabetes-an observational study.
AB  - OBJECTIVE: To compare low dose (0.05 units/kg/h) with standard dose (0.1
      units/kg/h) intravenous insulin infusion for the treatment of diabetic
      ketoacidosis (DKA) in children with type 1 diabetes. STUDY DESIGN: Data from five
      paediatric centres were compared in children who received 0.05 (41 episodes) or
      0.1 units/kg/h (52 episodes). RESULTS: In the low vs. standard dose group, at 6 h
      following admission, the fall in blood glucose levels [11.3 (95% confidence
      interval 8.6 to 13.9) vs. 11.8 (8.4 to 15.2) mmol/L, p = 0.86] and rise in pH
      [0.13 (0.09 to 0.18) vs. 0.11 (0.07 to 0.15), p = 0.78] were similar. These
      changes were comparable between doses in relation to: severity of initial
      acidosis, children newly diagnosed with diabetes or aged less than 5 years. After
      adjustment for other clinical and biochemical covariates, insulin dose was
      unrelated to the change in pH and blood glucose levels at 6 h following
      admission. Comparisons of safety data, particularly in relation to abnormal
      Glasgow Coma Score, were inconclusive. CONCLUSION: In this observational study,
      low dose was as effective as standard dose intravenous insulin infusion in the
      initial treatment (less than 6 h) of DKA in children with type 1 diabetes. A
      randomised controlled trial is required to show true equivalence between doses
      and to evaluate potential safety benefits.

PMID- 19602157
TI  - Sudden cardiac arrest in the young due to inherited arrhythmias: the importance
      of family care.
AB  - BACKGROUND: Sudden cardiac arrest in the young is always an extremely tragic
      event, producing enormous stress and anxiety in the family. When the event is due
      to an inherited cardiac arrhythmia, the additional concerns and questions about
      who else is affected and who will die next can become overwhelming to both the
      nuclear and the extended family. Identification and screening of the family
      members are necessary in order to find and treat presymptomatic members and
      prevent sudden death. METHODS: Guidelines and strategies for care of the extended
      family are presented. RESULTS: Pedigree development and expansion, followed by
      prospective contacting of family members and screening by phenotyping and
      genotyping, allow recognition and treatment of many mutation carriers who would
      not otherwise come to medical attention unless they develop a serious cardiac
      event. Presymptomatic treatment of affected members is highly efficacious and
      prevents sudden deaths. CONCLUSIONS: Sudden cardiac arrest due to inherited
      arrhythmia disorders can be prevented by prospective, structured evaluation of
      the extended family, allowing effective, presymptomatic, and prophylactic
      treatment of the affected members to be provided.

PMID- 19602158
TI  - Sudden cardiac death in children and adolescents: introduction and overview.

PMID- 19602159
TI  - Hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is one of the most common inherited
      cardiac disorders, with a prevalence in young adults of one in 500 and is defined
      by its wall thickening. METHODS: This chapter of the supplement will present
      major clinical impacts of this disorder in its predilection to be inherited; its
      reputation as the most common cause of sudden death in young, healthy, athletic
      individuals; and its potential to develop heart failure due to either diastolic
      or systolic dysfunction, so-called "burned out" HCM. Underlying etiologies;
      diversity of morphologic, functional, and clinical features; and variable age of
      onset that differentiate the childhood from the adult form of disease will be
      discussed based on the literature and clinical experience. RESULTS: In children
      less than 1 year of age, hypertrophy associated with systolic dysfunction is
      common. In contradistinction, among apparently healthy young adults, the
      prevalence of echcocardiographically defined HCM was reported to be as high as
      0.2% and associated with diastolic dysfunction. In addition, overlaping disorders
      such as infiltrative and energy-dependent forms of HCM coexist with other
      atypical features in childhood, further confounding the presentations,
      treatments, and outcomes compared to adult disease. CONCLUSION: HCM in childhood
      has a variety of etiologies which may influence diagnostic testing, treatments,
      and outcomes.

PMID- 19602153
TI  - Phylogenetic analysis identifies many uncharacterized actin-like proteins (Alps)
      in bacteria: regulated polymerization, dynamic instability and treadmilling in
      Alp7A.
AB  - Actin, one of the most abundant proteins in the eukaryotic cell, also has an
      abundance of relatives in the eukaryotic proteome. To date though, only five
      families of actins have been characterized in bacteria. We have conducted a
      phylogenetic search and uncovered more than 35 highly divergent families of actin
      like proteins (Alps) in bacteria. Their genes are found primarily on phage
      genomes, on plasmids and on integrating conjugative elements, and are likely to
      be involved in a variety of functions. We characterize three Alps and find that
      all form filaments in the cell. The filaments of Alp7A, a plasmid partitioning
      protein and one of the most divergent of the Alps, display dynamic instability
      and also treadmill. Alp7A requires other elements from the plasmid to assemble
      into dynamic polymers in the cell. Our findings suggest that most if not all of
      the Alps are indeed actin relatives, and that actin is very well represented in
      bacteria.

PMID- 19602160
TI  - Sudden cardiac death in dilated cardiomyopathies.
AB  - Dilated cardiomyopathy (DCM) is the most prevalent form of cardiomyopathy, and
      sudden cardiac death (SCD) remains a common event in young patients. The disorder
      is highly heterogeneous and pediatric DCM often differs from adult DCM in
      etiologies, risk factors, and prognosis. Prognosis may be improving, likely
      secondary to specialized management. Both traditional and novel markers of risk
      have been studied in adults and are beginning to be applied to children with DCM.
      The major therapy for patients considered at risk remains implantable
      cardioverter-defibrillator (ICD) placement, although frequently this functions as
      a bridge to eventual transplantation.

PMID- 19602161
TI  - Restrictive cardiomyopathy.
AB  - BACKGROUND: Restrictive cardiomyopathy is characterized by ventricular diastolic
      dysfunction with a clinical course in childhood that is often progressive despite
      medical therapy. METHODS: A review of the literature and clinical experience was
      used to summarize the natural history of this oftentimes devastating disease with
      a focus on diagnostic tools and therapeutic options. RESULTS: The clinical
      presentation of restrictive cardiomyopathy can be highly variable, ranging from
      asymptomatic to overt signs of heart failure with pulmonary hypertension.
      Emerging noninvasive diagnostic tools are increasingly helpful yet there remains
      a role for invasive studies including cardiac catheterization with or without
      endomyocardial biopsy. A significant risk of sudden death exists and may not be
      limited to those with more pronounced symptoms. CONCLUSIONS: Children with
      restrictive cardiomyopathy require comprehensive evaluation with careful
      surveillance. Early listing for cardiac transplantation should be considered.

PMID- 19602162
TI  - Arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) has evolved from
      postmortem pathology at to a diagnosable clinical condition, and holds promise
      for definitive genetic diagnosis. Its prevalence is between 1/1,000 and 1/5,000,
      with 10% of deaths occurring before age 19 and 50% before age 35. When analyzed
      against age-specific norms, the electrocardiography (ECG) and signal-averaged ECG
      (SAECG) have moderate sensitivity for ARVC. Endomyocardial biopsy in young
      individuals with ARVC demonstrates fibrosis more frequently than fatty
      infiltration, and is convincing for the diagnosis in approximately 1/3 (often in
      patients who would not otherwise be diagnosed), but has a recognized complication
      rate of 2%. Newer technologies of magnetic resonance imaging and voltage mapping
      hold promise but require further assessment in young individuals suspected to
      have ARVC. Genetic diagnosis of one of several desmosomal mutations is positive
      in an approximately 50% of suspected patients, and may provide clues to the
      pathophysiology of the disease. Serial studies of myocardial function, ambulatory
      electrocardiography, and SAECG parameters may be useful in risk stratification of
      identified patients, although their applicability to genetically identified
      asymptomatic individuals has not been studied.

PMID- 19602163
TI  - The long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.
AB  - Thanks to the contribution of molecular genetics, the genetic bases, the
      pathogenesis and genotype-phenotype correlation of diseases such as the long QT
      syndrome and catecholaminergic polymorphic ventricular tachycardia have been
      progressively unveiled and show an extremely high degree of genetic
      heterogeneity. Data from clinical registries are summarized together with the
      recommendations provided in clinical practice guidelines for management of
      patients with these diseases. Furthermore the evidence supporting the importance
      of genetic analysis for risk stratification and therapy selections is reviewed.

PMID- 19602164
TI  - Brugada and short QT syndromes.
AB  - Brugada syndrome and short QT syndrome are among the rarer cardiac
      channelopathies that may result in sudden cardiac arrest. The genetics and
      molecular mechanisms of these diseases provide insight into the mechanisms of
      more common channelopathies, and may dictate special therapeutic approaches with
      respect to drug therapy and risk stratification.

PMID- 19602165
TI  - The role of ECG screening in the evaluation of risk of sudden cardiac arrest in
      the young.
AB  - We have the opportunity to answer the questions that have been raised and obtain
      answers by prospective evaluation. ECG screening does not need an all-or-none
      approach in the current era. It needs a commitment to obtain the relevant data
      that will be accepted as applicable in the United States. Multiple populations,
      genders, ages, ethnicities, and races should be screened in a prospective ECG
      screening study. The actual costs should be obtained and cost utility analysis
      should be performed. Models of screening should be developed and tested. It is no
      longer acceptable to say "It can't be done here"; or "It costs too much"; or any
      of the scores of excuses used unless one can support the statements with trials
      or scientific data. A study of 100,000 children ages 5-19 years would cost
      $500,000-750,000. Is it not worth finding out who is correct, how to better
      identify those at risk, and how to do it in the most cost-efficient manner? No
      one wants to waste $2 billion a year. However, a one-time investment of 25% of
      that amount would determine how best to use our health care resources in the
      future to identify children and youth at risk for SCA.

PMID- 19602167
TI  - Implantable cardioverter defibrillator criteria for primary and secondary
      prevention of pediatric sudden cardiac death.
AB  - The implantable cardioverter defibrillator is established as life-saving in
      specific adult populations. However, the precise indications and criteria for
      defibrillator implantation in children are less well defined. This article
      provides a succinct review of the indications and implantation criteria in
      pediatric populations at risk for sudden cardiac death, including specific
      disease substrates such as cardiomyopathies, inherited arrhythmias, and
      congenital heart disease.

PMID- 19602166
TI  - Congenital coronary artery abnormalities predisposing to sudden cardiac death.
AB  - Isolated congenital coronary artery anomalies (CCAAs) are a rare but well
      described cause of sudden cardiac death (SCD). Anomalous origin of a coronary
      artery from the opposite sinus has been most frequently associated with
      myocardial ischemia, ventricular arrhythmias, and sudden death, particularly when
      the anomalous coronary courses between the great arteries. Importantly, symptoms
      occur in only about 50% of people with CCAA who subsequently have SCD.
      Echocardiography is effective in prospectively identifying these coronary artery
      abnormalities but requires sophisticated echo equipment and a laboratory
      examination with targeted, high-quality imaging. Although surgical intervention
      for some forms of CCAA is feasible with good early results and is clearly
      indicated for symptomatic patients, no clear best practice has been established
      for the management of those identified serendipitously without symptoms.

PMID- 19602168
TI  - Implantable cardioverter defibrillator-related complications in the pediatric
      population.
AB  - BACKGROUND: The recognition that implantable cardioverter-defibrillator (ICD)
      therapy in children can prolong life coupled with the development of smaller
      devices and transvenous lead technology has increased the number of ICDs
      implanted in children and young adults. METHODS: ICD complications in the
      pediatric population are reviewed. RESULTS: ICD complications in the pediatric
      population include those related to the implantation procedure, the ICD system,
      as well as psychosocial issues. Inappropriate ICD therapy and ICD lead failures
      are the most frequent complications. CONCLUSION: Identifying complications is the
      prerequisite for advances in ICD technology and effective management strategies
      need to be developed to avoid their recurrence.

PMID- 19602169
TI  - Automated external defibrillators utility, rational, and controversies.
AB  - Automated external defibrillators (AEDs) and their role in resuscitation has been
      documented in the adult population with the reported beneficial outcomes
      documented in multiple studies. Data for children are lacking because of the
      relatively small incidence of cardiac arrest in the pediatric population as well
      as the absence of randomized studies. There have been a few studies that have
      reviewed sudden cardiac arrest in the school setting as well the use and efficacy
      of AEDs. This article will review the data with regard to cardiac arrest in the
      school settings as well as the potential benefits of school CPR-AED programs.
      There are multiple criticisms and potential barriers of school CPR-AED programs.
      The specific criticisms will be addressed.

PMID- 19602170
TI  - Psychosocial considerations for children and young adolescents with implantable
      cardioverter defibrillators: an update.
AB  - BACKGROUND: The extension of the life-saving benefits of the implantable
      cardioverter-defibrillator (ICD) to prevent sudden cardiac arrest in children and
      young adults represents a key clinical development. The psychosocial adjustment
      in young ICD patients has not been as well-studied as in adults and remains an
      area of needed research. METHODS: The current paper reviews the quantitative
      research regarding ICD patient psychosocial outcomes in the adult and pediatric
      literature, and highlights existing intervention research on adult ICD patients
      and its implications for young ICD patients. RESULTS: Literature review indicates
      that anxiety may be the most problematic psychosocial reaction for young ICD
      patients, similar to adult patients. Since young ICD patients appear to be more
      likely to experience shocks than adults; shock-related anxiety is suspected to be
      particularly common. Interventions in adults have shown a reduction in anxiety
      but no pediatric intervention studies are currently available in the literature.
      CONCLUSION: Additional research and clinical attention is warranted to further
      assist young ICD patients to achieve desirable quality of life outcomes.

PMID- 19602171
TI  - Patient advocacy: what is its role?
AB  - While there are significant differences in the delivery of health care throughout
      the world, there is one constant, the patient. Patients' needs vary greatly on
      the basis of socioeconomic and geographic issues, expected prognosis, family
      dynamics, health literacy, and many other factors. In the past 20 years, the role
      of patient advocacy organizations has added an important new dynamic to patient
      care. Understanding patient advocacy organizations and how to access their
      services can be beneficial to clinicians, researchers, and patients. Critical
      issues are (1) closer collaboration and partnership with physician organizations,
      like PACES, in order to improve individual patient care and the quality of care
      that physicians are able to deliver; (b) work with physicians, physician
      organizations, and advocacy groups to measure the impact of advocacy groups; and
      (3) increase community-based participatory research.

PMID- 19602172
TI  - State of postmortem genetic testing known as the cardiac channel molecular
      autopsy in the forensic evaluation of unexplained sudden cardiac death in the
      young.
AB  - BACKGROUND: Thousands of infants, children, adolescents, and young adults die
      sudden and unexpectedly each year in the United States. A significant proportion
      are autopsy negative and are classified as autopsy negative sudden unexplained
      death (SUD) after the first year of life and as sudden infant death syndrome
      (SIDS) if prior to their first birthday. Postmortem genetic testing known as the
      cardiac channel molecular autopsy is capable of identifying the subset of
      channelopathic SUD/SIDS. METHODS: Review of the literature and analysis of the
      state of such postmortem genetic testing in the evaluation of SUD/SIDS. RESULTS:
      Although still confined to anecdotal reports, relatively small case series of
      coroner/medical examiner-referred cases of SUD/SIDS, and one population-based
      cohort of SIDS, it is estimated that approximately 25-35% of autopsy-negative SUD
      and approximately 10% of SIDS may stem from mutations in either long QT syndrome
      (LQTS)- or catecholaminergic polymorphic ventricular tachycardia (CPVT)
      susceptibility genes. DISCUSSION: Whether the cardiac channel molecular autopsy
      should become the standard of care in the postmortem evaluation of autopsy
      negative SUD or SIDS will require further scrutiny. Cost effectiveness analyses
      of a more intense postmortem focus on the decedent compared to the current
      battery of tests recommended for the deceased SUD victim's first degree relatives
      should be performed. CONCLUSION: If deemed justified to upgrade such postmortem
      genetic testing from "investigational" to clinically indicated, uniform "standard
      operating procedures" to ensure that tissue is acquired and archived in a manner
      that is "DNA friendly" and insurance coverage that extends beyond one's final
      breath will be needed.

PMID- 19602173
TI  - Antisense suppression of type 1 diacylglycerol acyltransferase adversely affects
      plant development in Brassica napus.
AB  - Diacylglycerol acyltransferase (DGAT) catalyzes the acyl-coenzyme A (CoA)
      dependent acylation of sn-1,2-diacylglycerol to form triacylglycerol in the
      terminal step of seed oil formation. Previous work has suggested that the level
      of DGAT activity may have a substantial effect on the flow of carbon into
      triacylglycerol, implying that the enzyme may represent a promising target for
      seed oil modification through biotechnological approaches. In the current study,
      Brassica napus DH12075 was transformed with an antisense type 1 DGAT construct,
      resulting in a reduction in DGAT1 gene expression, total DGAT activity and seed
      oil content. In addition, reduced seed yield and germination rates were observed
      along with severe developmental abnormalities. These data suggest that in
      addition to its critical role in seed oil formation, DGAT1 enzyme may also be
      important for normal seed development in B. napus, although the underlying
      mechanism(s) remain to be determined.

PMID- 19602174
TI  - Water relations of the tos1 tomato mutant at contrasting evaporative demand.
AB  - The tos1 (tomato osmotically sensitive) mutant, isolated from an in vitro screen
      of root growth during osmotic stress, was less sensitive to exogenous ABA, but
      accumulated more ABA under osmotic stress than WT plants. We assessed growth and
      water relations characteristics of hydroponically grown tos1 seedlings (in the
      absence of osmotic stress) at low and high evaporative demands. Growth of tos1
      was severely inhibited at both high and low evaporative demands. Twenty DAS, WT
      and tos1 genotypes had a similar leaf water and turgor potential, but mature tos1
      plants (45 day old) showed a significant diurnal loss of leaf turgor, with
      recovery overnight. Increased evaporative demand increased turgor loss of tos1
      plants. High evaporative demand at the beginning of the day decreased stomatal
      conductance of tos1, without diurnal recovery, thus whole plant transpiration was
      decreased. De-topped tos1 seedlings showed decreased root hydraulic conductance
      and had a 1.4-fold increase in root ABA concentration. Impaired root function of
      tos1 plants failed to meet transpirational water demand and resulted in shoot
      turgor loss, stomatal closure and growth inhibition.

PMID- 19602176
TI  - Clinical and pathological findings of a sac-like formation in the tunica
      vaginalis of a Nelore (Bos indicus) bull.
AB  - A seven-month-old purebred Nelore calf was diagnosed with a bilateral finger
      shaped swelling although more prominent at the left side of the scrotum, located
      longitudinal and parallel to epididymis corpus. The finding was present from 7
      months of age up to castration (performed at 25 months of age). Scrotal
      circumference, testicular and epididymis consistency and symmetry as well as
      seminal quality were normal during the follow-up period. The ultrasonographic
      appearance of the scrotal wall, pampiniform plexus, gonad and epididymis was
      normal. However, an anechoic region surrounded by a wall forming a sac-like
      structure with a blind end at its dorsal pole was seen on the swelling area. The
      examination of fluid aspirated from the saccular contents revealed the presence
      of mononuclear cells mainly from lymphocytic and histiocytic type as well as some
      loosing degenerated mesothelial cells. Gross examination at castration revealed a
      blind sac-like appendix derived from an evagination in the parietal layer of the
      tunica vaginalis. The structure of approximately 5.0 cm in length extended from
      the dorsal edge of the epididymis cauda. No adherences with surrounded tissues
      were observed. Histopathology of the sac wall showed a smooth inner surface
      composed by scarce mesothelial cells forming in some areas papillary-like
      projections protruding to the vaginal cavity. Underneath, a thick layer of
      fibrous tissue mixed with collagen fibres and mononuclear inflammatory cells were
      seen. The potential consequences of this saccular formation at an older age in a
      bull are unknown.

PMID- 19602175
TI  - Interoceptive awareness declines with age.
AB  - Aging has been shown to increase sensory thresholds for a variety of
      exteroceptive and proprioceptive stimuli. However, the influence of aging on
      interoceptive awareness has received relatively little empirical attention. Here
      we report an inverse association between aging and interoception, as indexed by
      the ability to sense the heartbeat at rest. In a group of 59 participants ranging
      in age from 22 to 63 years, age inversely predicted heartbeat detection ability,
      both within and across several measurement sessions. On average, age accounted
      for 30% of the variance in heartbeat detection accuracy. Other attribute
      variables including body mass index and sex were not related to heartbeat
      detection ability. These findings provide clear empirical evidence that
      interoception, much like exteroception and proprioception, declines with age.

PMID- 19602177
TI  - Effect of roscovitine-treated donor cells on development of porcine cloned
      embryos.
AB  - Synchronization of the donor cell cycle is an important factor for successful
      animal cloning by nuclear transfer. To improve the efficiency of porcine cloning,
      in the present report, we evaluated effects of contact inhibition, serum
      starvation and roscovitine treatment of donor cells on in vitro and in vivo
      developmental potency of cloned porcine embryos. Fibroblasts derived from a
      porcine foetus at day 30 of gestation were isolated and cultured to 70%
      confluency. Then, cells were either cultured to 100% confluency for contact
      inhibition, or cultured in 0.5% serum for 72 h for serum starvation or with 15
      MUM roscovitine for 24 h. Cells were most effectively synchronized at G0/G1 in
      the serum starvation group (87.5%) compared with the contact inhibition and
      roscovitine treatment groups (76.3% and 79.9% respectively p < 0.05). However,
      after somatic cell nuclear transfer followed by in vitro culture, the serum
      starvation group showed a significantly lower blastocyst formation rate (5.6%)
      compared with the contact inhibition and roscovitine treatment groups (11.6% and
      20.0% respectively). Differential expression of apoptosis-related genes and the
      level of apoptosis in each treatment group explain the variation in developmental
      competence among the groups. Significantly higher level of apoptosis was observed
      in the serum starvation group. On the other hand, the roscovitine treatment group
      shows the lowest level of apoptosis and the best in vitro development among the
      groups. Cloned embryos derived from roscovitine-treated donor cells were
      transferred to surrogate pigs. Three healthy live piglets were produced. In
      conclusion, we suggest that roscovitine treatment of donor cells improves
      development of cloned porcine embryos and can raise the efficiency of cloned
      piglet production.

PMID- 19602178
TI  - Effect of cyclin-dependent kinase (CDK) inhibition on expression, localization
      and activity of maturation promoting factor (MPF) and mitogen activated protein
      kinase (MAPK) in bovine oocytes.
AB  - This study aimed to assess the effects of cyclin-dependent kinase (CDK)
      inhibition on factors involved in the control of meiosis in bovine oocytes:
      maturation promoting factor (MPF) (p34(cdc2) and cyclin B1) and mitogen activated
      protein kinase (MAPK). Oocytes were maintained at germinal vesicle (GV) stage in
      vitro with 10 MUM of the CDK inhibitor butyrolactone I (BLI) for 24 h
      (inhibited). After this period, some of the oocytes were transferred to in vitro
      maturation (IVM) culture for 24 h (inhibited and matured). Control oocytes were
      assessed immediately after follicle aspiration (immature) or after in vitro
      maturation for 24 h (matured). Real-time PCR analyses showed that transcripts for
      p34(cdc2) and MAPK were detected in immature and inhibited oocytes and decreased
      after maturation, irrespective of CDK inhibition with BLI. Cyclin B1 was detected
      at similar levels in all oocyte groups. The p34(cdc2) and MAPK proteins were
      detected by Western blotting at similar levels in all oocyte groups, and cyclin
      B1 protein was detected only after maturation. Immunofluorescence detection
      showed that p34(cdc2) was localized in the cytoplasm and GV of immature oocytes,
      and then throughout the cytoplasm after maturation. Cyclin B1 and MAPK were
      detected in the cytoplasm in all oocyte groups. Maturation promoting factor and
      MAPK activities were similar throughout most of maturation for oocytes treated
      with or without BLI. In conclusion, CDK inhibition did not affect the expression
      (mRNA and protein levels) and localization of MPF and MAPK, and had nearly no
      effect on kinase activities during maturation.

PMID- 19602179
TI  - Vaginal neurofibroma in a hysterectomized poodle dog.
AB  - A 15-year-old, spayed, female poodle dog was presented for evaluation of a mass
      of tissue prolapsed from the vulva. The dog had been hysterectomized when it was
      5 years old. A vaginal mass had been removed approximately 10 months before
      presentation. Haematological and serum biochemistry analyses demonstrated mild
      leucocytosis and glycaemia. A vaginal smear was predominantly made up of
      parabasal cells and intermediate cells with no neoplastic cells. Thoracal and
      abdominal radiographic findings were unremarkable. The ovaries could not be
      identified using abdominal ultrasonography. A midline exploratory laparotomy
      identified both ovaries that were surgically excised. The vaginal mass was also
      removed following an episiotomy procedure. Histopathological examination of the
      mass demonstrated that it was a neurofibroma. Both ovaries had cystic changes.
      Four months after the surgery, the owner reported that the dog was clinically
      normal. To the authors' knowledge, this is the first reported case of a vaginal
      neurofibroma after an incomplete ovariohysterectomy in the dog.

PMID- 19602180
TI  - Integration between different hypothalamic nuclei involved in stress and GnRH
      secretion in the ewe.
AB  - This study investigated possible integrated links in the neuroanatomical pathways
      through which the activity of neurones in the paraventricular nucleus and arcuate
      nucleus may modulate suppression of gonadotrophin-releasing hormone (GnRH)
      secretion during stressful situations. Double-label immunofluorescence and laser
      scanning confocal microscopy were used to examine the hypothalamic sections from
      the follicular phase ewes. Noradrenergic terminals were in close contact with
      65.7 +/- 6.1% corticotrophin-releasing hormone (CRH) and 84.6 +/- 3.2% arginine
      vasopressin (AVP) cell bodies in the paraventricular nucleus but not with beta
      endorphin cell bodies in the arcuate nucleus. Furthermore, gamma-amino butyric
      acid (GABA) terminals were close to 80.9 +/- 3.5% CRH but no AVP cell bodies in
      the paraventricular nucleus, as well as 60.8 +/- 4.1%beta-endorphin cell bodies
      in the arcuate nucleus. Although CRH, AVP and beta-endorphin cell terminals were
      identified in the medial pre-optic area, no direct contacts with GnRH cell bodies
      were observed. Within the median eminence, abundant CRH but not AVP terminals
      were close to GnRH cell terminals in the external zone; whereas, beta-endorphin
      cells and terminals were in the internal zone. In conclusion, neuroanatomical
      evidence is provided for the ewe supporting the hypothesis that brainstem
      noradrenergic and hypothalamic GABA neurones are important in modulating the
      activity of CRH and AVP neurones in the paraventricular nucleus, as well as beta
      endorphin neurones in the arcuate nucleus. These paraventricular and arcuate
      neurones may also involve interneurones to influence GnRH cell bodies in medial
      pre-optic area, whereas the median eminence may provide a major site for direct
      modulation of GnRH release by CRH terminals.

PMID- 19602181
TI  - Development of Y-chromosome-specific SCAR markers conserved in taurine, zebu and
      bubaline cattle.
AB  - Sex pre-selection of bovine offsprings has commercial relevance for cattle
      breeders and several methods have been used for embryo sex determination.
      Polymerase chain reaction (PCR) has proven to be a reliable procedure for
      accomplishing embryo sexing. To date, most of the PCR-specific primers are
      derived from the few single-copy Y-chromosome-specific gene sequences already
      identified in bovines. Their detection demands higher amounts of embryonic
      genomic material or a nested amplification reaction. In order to circumvent this,
      limitation we searched for new male-specific sequences potentially useful in
      embryo sexing using random amplified polymorphic DNA (RAPD) analysis. Random
      amplified polymorphic DNA (RAPD) assay reproducibility problems can be overcome
      by its conversion into Sequence Characterized Amplified Region (SCAR) markers. In
      this work, we describe the identification of two bovine male-specific markers
      (OPC16(323) and OPF10(1168)) by means of RAPD. These markers were successfully
      converted into SCARs (OPC16(726) and OPF10(984)) using two pairs of specific
      primers.Furthermore, inverse PCR (iPCR) methodology was successfully applied to
      elongate OPC16(323) marker in 159% (from 323 to 837 bp). Both markers are shown
      to be highly conserved (similarity >=95%) among bovine zebu and taurine cattle;
      OPC16(323) is also highly similar to a bubaline Y-chromosome-specific sequence.
      The primers derived from the two Y-chromosome-specific conserved sequences
      described in this article showed 100% accuracy when used for identifying male and
      female bovine genomic DNA, thereby proving their potential usefulness for bovine
      embryo sexing.

PMID- 19602182
TI  - An index for breathlessness and leg fatigue.
AB  - The features of perceived symptoms causing discontinuation of strenuous exercise
      have been scarcely studied. The aim was to characterize the two main symptoms
      causing the discontinuation of heavy work in healthy persons as well as describe
      the growth of symptoms during exercise. Breathlessness (b) and leg fatigue (l)
      were assessed using the Borg CR10 Scale and the Borg CR100 (centiMax) Scale,
      during a standardized exercise test in 38 healthy subjects (24-71 years). The b/l
      relationships were calculated for terminal perceptions (ERI(b/l)), and the growth
      of symptoms determined by power functions for the whole test, as well as by
      growth response indexes (GRI). This latter index was constructed as a ratio
      between power levels corresponding to a very strong and a moderate perception. In
      the majority (71%) of the test subjects, leg fatigue was the dominant symptom at
      the conclusion of exercise (P<0.001) and the b/l ratio was 0.77 (CR10) and 0.75
      (CR100), respectively. The GRI for breathlessness and leg fatigue was similar,
      with good correlations between GRI and the power function exponent (P<0.005). In
      healthy subjects, leg fatigue is the most common cause for discontinuing an
      incremental exercise test. The growth functions for breathlessness and leg
      fatigue during work are, however, almost parallel.

PMID- 19602183
TI  - Development and validation of the French Self-Regulatory Eating Attitude in
      Sports Scale.
AB  - In this study, the French Self-Regulatory Eating Attitude in Sports Scale
      (SREASS) was developed and then validated. Five subscales measure the control of
      eating attitude in contexts of: (a) food temptation, (b) negative affects, (c)
      social interaction, (d) lack of compensatory strategy, and (e) lack of
      anticipation of consequences on performance. The validation procedure required
      the participation of 527 student athletes and four successive studies to develop
      and present a preliminary scale and assess the clarity of the items (study 1),
      evaluate the factorial structure validity of the scale and test the invariance
      across gender (study 2), assess the time stability (study 3), and assess the
      external validity of the instrument (study 4). The present results provide
      preliminary evidence for the appropriateness of the SREASS for French student
      athletes. Nevertheless, further evaluation of this instrument is warranted to
      establish the robustness of the present findings.

PMID- 19602184
TI  - Is there a secular decline in motor skills in preschool children?
AB  - Current research seems to confirm a secular decline in movement skills in school
      children. Only few data are available for preschool children and no clear trend
      can be identified. In the year 2007, height, weight, and motor performance were
      determined in 726 preschool children [Prevention through Activity in Kindergarten
      Trial (PAKT)] and compared with historical samples from 1973, 1985, and 1989.
      There was no difference in height and weight between the samples of 1973 and
      2007. Older boys of today were smaller and lighter than those of 1989. Regardless
      of age, PAKT children fared significantly better in standing long jump than those
      assessed in 1989. Compared with the sample of 1973, PAKT children did equally
      well in this task. There were no differences in performance in an obstacle course
      between children of 1989 and 2007. In balancing backwards, PAKT children
      performed significantly worse than those in 1985. Regarding target throwing only
      the PAKT 4-year-olds achieved significantly worse results than those in
      1985.Therefore, in preschool children, a secular decline is only evident in some,
      but not all, motor skills, which may indicate a change in behavior activity over
      the last decades.

PMID- 19602185
TI  - Eccentric exercise protocols for chronic non-insertional Achilles tendinopathy:
      how much is enough?
AB  - Eccentric exercises for the calf muscles have been shown to be effective for
      chronic non-insertional Achilles tendinopathy (AT). However, the relative
      effectiveness of various dosages is unknown. A systematic review of randomized
      controlled trials (RCTs) was designed to determine whether an optimum dose of
      eccentric exercises could be recommended. Three selected RCTs showed positive
      effects of very similar eccentric exercise protocols for chronic non-insertional
      AT. Owing to insufficient reported compliance data, a conclusion on the relative
      effectiveness of various compliances was not feasible. According to our review,
      the relative effectiveness of various dosages of eccentric exercises for AT is
      still unclear. However, it appears that highly variable compliance rates result
      in similar positive outcomes; these findings, therefore, highlight the need for
      further investigations.

PMID- 19602186
TI  - Relative age effect in female sport: a diachronic examination of soccer players.
AB  - The relative age effect (RAE) is a biased distribution of elite athletes'
      birthdates, with an overrepresentation of those born at the beginning of the
      competitive year and an underrepresentation of those born at the end. Despite an
      abundant literature, the impact of sex on this phenomenon remains neglected by
      most researchers. This study investigated the whole sample of female soccer
      players affiliated to the French Soccer Federation for the 2006-2007 season (n=57
      892). It first aimed at testing the presence of RAE depending on age. Next, we
      looked at the birthdates of dropout players during the next season (n=15 285), to
      test whether relative age accounts for dropout from the activity. The analyses
      revealed significant differences between the expected and the observed
      distributions for all age categories. Furthermore, a significantly biased
      distribution of dropout players' birthdates was found for the <10, <14, and <17
      categories. On the whole, dropout players are underrepresented in Q1 and Q2, but
      overrepresented in Q3 and Q4. This study completes the literature on RAE among
      females, but the inconsistency of the results calls for more research on this
      population.

PMID- 19602188
TI  - Acute effects of whole-body vibration on peak isometric torque, muscle twitch
      torque and voluntary muscle activation of the knee extensors.
AB  - The purpose of this investigation was to compare the acute effects of whole-body
      vibration (WBV) with a static squat on resting muscle twitch torque, peak
      isometric torque and voluntary muscle activation of the knee extensors during an
      isometric maximal voluntary contraction (MVC). Twenty-four healthy, strength
      trained males were recruited for this randomized, cross-over design
      investigation. The WBV treatment consisted of three sets of 60 s of vibration (30
      Hz, +/-4 mm) while standing in a semi-squat position. Voluntary muscle
      activation, peak isometric torque during MVC and resting muscle twitch torque
      (RTT) through percutaneous femoral nerve stimulation were obtained before and
      following the treatment. Change in peak isometric torque, voluntary muscle
      activation and the RTT were calculated as the difference between pre- and post
      treatment values. There was no observable post-activation potentiation of muscle
      twitch torque or enhancement in voluntary muscle activation or peak isometric
      torque. However, decreases in the peak isometric torque (P=0.0094) and voluntary
      muscle activation (P=0.0252) were significantly smaller post WBV interventions
      compared with the control treatment. Based on the current data, it is unclear
      whether or not this was attributable to the effects of WBV but further research
      into this possibility is warranted.

PMID- 19602187
TI  - Energy intake and expenditure during a 6-day cycling stage race.
AB  - Energy intake (EI) and energy expenditure (EE) are relatively easy to measure
      accurately over short periods in a laboratory setting, but less so during a multi
      day competition. Our goal was to measure EI and EE as accurately as possible
      during a 6-day, 10-stage cycling race. We prepared all meals and supplements,
      assessed EI (weighed diet-records) and macrontrient intake, total EE (doubly
      labelled water), resting metabolic rate (respiratory gas exchange), exercise EE
      (power meters), and body mass. Body composition was measured several days before
      and after racing (dual x-ray absorptiometry). Body mass remained stable over the
      course of the race. The mean EI (27.3+/-3.8 MJ/day) nearly matched EE (27.4+/-2.0
      MJ/day). The majority (62%) of EE was exercise EE. Macronutrient intake was
      within or exceeded the recommendations. Lean body mass increased and fat mass
      decreased in most of our participants. Our study indicates that EI can match high
      EE with adequate macronutrient intake during multi-day cycle racing and may be
      facilitated by appropriate foods being available at appropriate times. This
      optimization of nutritional provision supports positive changes in body
      composition.

PMID- 19602190
TI  - Does a drop landing represent a whole skill landing and is this moderated by
      fatigue?
AB  - This study aimed to determine whether the landing phase of a drop landing (DL)
      differed with respect to a complete jumping and landing task, a spike jump (SJ),
      and whether fatigue altered the landing of these movements. Fourteen male
      volleyball players performed five DL and SJ in a counterbalanced order under two
      experimental conditions: non-fatigued and fatigued. Fatigue, induced by
      repetitive jumping sets, was confirmed by decrements in vertical jump height >25%
      and increased blood lactate >6 mmol/L. Each landing task was characterized by the
      resultant ground reaction forces (GRF), sagittal plane kinematics and muscle
      recruitment patterns of six lower extremity muscles. Two-way repeated analysis of
      variance results indicated a main effect of movement on many of the GRF,
      kinematic and electromyographic variables characterizing landing, indicating that
      the two tasks required substantially different lower limb biomechanics during
      landing. Although fatigue did not alter the GRF in either task, there were
      significant movement x fatigue condition interactions. The significant between
      task differences in the biomechanical variables characterizing landing and the
      differential effects of fatigue on each landing task, question the validity of
      using a DL as an experimental task to investigate lower limb landing mechanics of
      whole jumping and landing movements.

PMID- 19602189
TI  - Basic concepts about genes, inactivity and aging.
AB  - Remarkably, 80-year-old humans who have partaken in lifelong aerobic or strength
      training have maximal aerobic capacities or muscle strengths comparable with that
      of sedentary individuals aged 50 or 55-year-old, respectively. Such delays in
      functional aging are clinically significant because lower aerobic and lower
      strength capacities increase the risk of premature death. In this short review,
      we speculate that the lack of daily physical activity induces evolutionarily
      selected mechanisms to use or lose, one of which is related to nutritional
      status.

PMID- 19602191
TI  - Type of sport is related to injury profile: a study on cross country skiers,
      swimmers, long-distance runners and soccer players. A retrospective 12-month
      study.
AB  - This 12-month retrospective questionnaire compared the occurrence of sports
      injuries in 149 cross country skiers, 154 swimmers, 143 long-distance runners and
      128 soccer players aged 15-35 years. Soccer had significantly more injuries (5.1
      injuries/1000 exposure hour) than other sports (2.1-2.8, P<0.001). More runners
      than soccer players reported overuse injuries (59% vs 42%, P=0.005), locating
      typically in the foot in runners, soccer players and skiers. Swimmers reported
      overuse injuries in the shoulder more commonly than skiers (40% vs 1%, P<0.001),
      who also intensively load shoulders. Acute injuries in skiers (80%) and in
      swimmers (58%), and overuse injuries in skiers (61%), occurred during exercise
      other than own event. In soccer and running the absence time from sport because
      of injuries was significantly longer than in skiing and swimming. No severe
      permanent disabilities occurred due to injury but seven women quit sports because
      of injury. In conclusion, type of loading is strictly associated with the
      anatomical location of an overuse injury as shown by the difference in shoulder
      injury incidence between swimmers and cross country skiers. In some sports, a
      significant proportion of acute injuries occur in other than the main event.

PMID- 19602192
TI  - Prolonged immobilization compromises up-regulation of repair genes after tendon
      rupture in a rat model.
AB  - It was hypothesized that mobilization vs immobilization after injury would
      promote tissue healing by regulating gene expression for molecules associated
      with repair. Cast immobilization vs free mobilization was studied after rat
      Achilles tendon rupture. Reverse transcriptase-polymerase chain reaction was
      performed at 8 and 17 days post-rupture to assess different growth factors [brain
      derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), nerve
      growth factor (NGF) and insulin-like growth factor-1 (IGF-1)] and inflammatory
      mediators [cyclooxygenase 1 and 2 (COX 1 and COX 2), inducible nitric oxide
      synthase and hypoxia-inducible factor-1alpha (HIF-1alpha)] in the healing region.
      At 8 days post-injury, tendon mRNA levels were comparable in both groups.
      However, by day 17, the mRNA levels for BDNF, bFGF, COX 1 and HIF-1alpha in the
      mobilized group had increased significantly. Corresponding mRNA levels in the
      immobilized group decreased during the same period. There were no significant
      differences in the expression of NGF, IGF-1 or COX 2 between the different
      groups, indicating that injury-associated expression of these molecules is not
      overtly influenced by loading. This study supports the notion that prolonged
      immobilization post-rupture hampers the healing process by compromising the up
      regulation of repair gene expression in the healing tendon. It might be
      speculated that a shorter period of immobilization, i.e. 1 week, would not impair
      the healing process significantly. The findings support the current development
      of earlier and more active rehabilitation programs after tendon injuries.

PMID- 19602193
TI  - The upper extremity of the professional tennis player: muscle volumes, fiber-type
      distribution and muscle strength.
AB  - The effects of professional tennis participation on dominant and non-dominant
      upper extremity muscle volumes, and on fiber types of triceps brachii (lateral
      head) and vastus lateralis muscles were assessed in 15 professional tennis
      players. Magnetic resonance imaging (MRI, n=8) examination and dual-energy x-ray
      absorptiometry (DXA, n=7) were used to assess muscle volumes and lean body mass.
      Muscle fiber-type distribution assessed by biopsy sampling was similar in both
      triceps brachii (2/3 were type 2 and 1/3 type 1 fibers). The VL was composed of
      1/3 of type 2 and 2/3 of type 1 fibers. The dominant had 12-15% higher lean mass
      (DXA/MRI) than the non-dominant (P<0.05). Type 1, 2a and 2x muscle fibers of the
      dominant were hypertrophied compared with the non-dominant by 20%, 22% and 34%
      (all P<0.01), respectively. The deltoid, triceps brachii, arm flexors and forearm
      superficial flexor muscles of the dominant were hypertrophied (MRI) compared with
      the non-dominant by 11-15%. These muscles represented a similar fraction of the
      whole muscle volume in both upper extremities. Dominant muscle volume was
      correlated with 1RM on the one-arm cable triceps pushdown exercise (r=0.84,
      P<0.05). Peak power during vertical jump correlated with VL muscle fibers's cross
      sectional area (r=0.82-0.95, P<0.05).

PMID- 19602194
TI  - Differences in twitch potentiation between voluntary and stimulated quadriceps
      contractions of equal intensity.
AB  - This study compared the extent of twitch and M-wave potentiation (POT) between
      voluntary and stimulated quadriceps contractions performed at the same intensity.
      Sixteen healthy men completed 10-s isometric knee extensions at 40% of the
      maximal voluntary contraction torque under electrical stimulation and voluntary
      conditions. Single stimuli were delivered to the femoral nerve to evoke twitches
      before (PRE) and from 3 to 600 s after the end of each conditioning contraction.
      Changes in twitch contractile properties and M-wave characteristics were compared
      between the conditions. The extent of twitch peak torque POT was smaller for the
      stimulated (122+/-20% of PRE) than for the voluntary condition (133+/-20% of
      PRE). The magnitude of POT for the maximal rate of twitch torque development was
      also smaller for the stimulated trial. Rectus femoris M-wave amplitude was
      potentiated by the voluntary but not by the stimulated contraction. It was
      concluded that stimulated contractions resulted in smaller twitch and M-wave POT
      than voluntary contractions, despite equivalent torque output and duration. The
      spatially and temporally fixed recruitment of motor units with electrical
      stimulation and therefore the lower number of activated motor units compared with
      voluntary actions of equal intensity could explain the present findings.

PMID- 19602195
TI  - Quantification of nuclear protein transport using induced heterodimerization.
AB  - Trafficking of proteins between the cytoplasm and nucleus occurs exclusively
      across the nuclear pore complex of eucaryotic cells. Fundamental aspects of this
      process affect temporal and spatial parameters, the latter carried out by
      specific import [nuclear localization sequence (NLS)] and export [nuclear export
      sequence (NES)] sequences. In this study, we focused on the adaptation of a
      protein heterodimerization assay to kinetically measure Crm1-mediated nuclear
      export in living cells using the rapalog AP21967, a heterodimerizing agent and
      NLS- and NES-containing fusion proteins equipped with distinct AP21967-specific
      binding motifs. In HeLa cells, we observed rapid nuclear export of the NLS
      containing fusion protein in the presence of AP21967, with the extent of this
      process being a function of the number of AP21967-binding motifs. AP21967-induced
      nuclear export was specifically inhibited by the Crm1-binding molecule leptomycin
      B. Half maximal export was achieved after approximately 10 min. We further
      applied protein heterodimerization in HeLa cells to study induced NLS-mediated
      nuclear import. Only in the presence of heterodimerizer AP21967 nuclear import of
      a cytoplasmically localizing fusion protein was observed. Induced protein
      heterodimerization is thus a valuable tool to quantitatively study
      nucleocytoplasmic protein trafficking in cultured cells, in a non-invasive, time
      saving manner.

PMID- 19602196
TI  - The GAP domain and the SNARE, coatomer and cargo interaction region of the
      ArfGAP2/3 Glo3 are sufficient for Glo3 function.
AB  - The ArfGAP Glo3 is required for coat protein I vesicle generation in the Golgi
      endoplasmic reticulum (ER) shuttle. The best-understood role of Glo3 is the
      stimulation of the GTPase activity of Arf1. In this study, we characterized
      functional domains of the ArfGAP Glo3 and identified an interaction interface for
      coatomer, SNAREs and cargo in the central region of Glo3 (BoCCS region). The GAP
      domain together with the BoCCS region is necessary and sufficient for all vital
      Glo3 functions. Expression of a truncated Glo3 lacking the GAP domain results in
      a dominant negative growth phenotype in glo3Delta cells at 37 degrees C. This
      phenotype was alleviated by mutating either the BoCCS region or the Glo3
      regulatory motif (GRM), or by overexpression of ER-Golgi SNAREs or the ArfGAP
      Gcs1. The GRM is not essential for Glo3 function; it may act as an intrinsic
      sensor coupling GAP activity to SNARE binding to avoid dead-end complex formation
      at the Golgi membrane. Our data suggest that membrane-interaction modules and
      cargo-sensing regions have evolved independently in ArfGAP1s versus ArfGAP2/3s.

PMID- 19602198
TI  - Membrane contact sites between apicoplast and ER in Toxoplasma gondii revealed by
      electron tomography.
AB  - Toxoplasma gondii is an obligate intracellular parasite from the phylum
      Apicomplexa. A hallmark of these protozoans is the presence of a unique apical
      complex of organelles that includes the apicoplast, a plastid acquired by
      secondary endosymbiosis. The apicoplast is indispensible for parasite viability.
      It harbours a fatty acid biosynthesis type II (FAS II) pathway and plays a key
      role in the parasite lipid metabolism. Possibly, the apicoplast provides
      components for the establishment and the maturation of the parasitophorous
      vacuole, ensuring the successful infection of the host cell. This implies the
      presence of a transport mechanism for fast and accurate allocation of lipids
      between the apicoplast and other membrane-bound compartments in the parasite
      cell. Using a combination of high-pressure freezing, freeze-substitution and
      electron tomography, we analysed the ultrastructural organization of the
      apicoplast of T. gondii in relation with the endoplasmic reticulum (ER). This
      allowed us to clearly show the presence of four continuous membranes surrounding
      the apicoplast. We present, for the first time, the existence of membrane contact
      sites between the apicoplast outermost membrane and the ER. We describe the
      morphological characteristics of these structures and discuss their potential
      significance for the subcellular distribution of lipids in the parasite.

PMID- 19602200
TI  - Measuring and reporting the effect of an intervention: absolute measures.

PMID- 19602197
TI  - Mechanism and a peptide motif for targeting peripheral proteins to the yeast
      inner nuclear membrane.
AB  - Trm1 is a tRNA specific m(2)(2)G methyltransferase shared by nuclei and
      mitochondria in Saccharomyces cerevisiae. In nuclei, Trm1 is peripherally
      associated with the inner nuclear membrane (INM). We investigated the mechanism
      delivering/tethering Trm1 to the INM. Analyses of mutations of the Ran pathway
      and nuclear pore components showed that Trm1 accesses the nucleoplasm via the
      classical nuclear import pathway. We identified a Trm1 cis-acting sequence
      sufficient to target passenger proteins to the INM. Detailed mutagenesis of this
      region uncovered specific amino acids necessary for authentic Trm1 to locate at
      the INM. The INM information is contained within a sequence of less than 20 amino
      acids, defining the first motif for addressing a peripheral protein to this
      important subnuclear location. The combined studies provide a multi-step process
      to direct Trm1 to the INM: (i) translation in the cytoplasm; (ii) Ran-dependent
      import into the nucleoplasm; and (iii) redistribution from the nucleoplasm to the
      INM via the INM motif. Furthermore, we demonstrate that the Trm1 mitochondrial
      targeting and nuclear localization signals are in competition with each other, as
      Trm1 becomes mitochondrial if prevented from entering the nucleus.

PMID- 19602206
TI  - The Journal of Blood Services Management, a new administrative focus for
      TRANSFUSION.

PMID- 19602207
TI  - Exposed or not exposed--that is the question: evidence for resolving and abortive
      hepatitis C virus infections in blood donors.

PMID- 19602208
TI  - Double standard for double ABO grouping?

PMID- 19602204
TI  - Adaptor protein-2 interaction with arrestin regulates GPCR recycling and
      apoptosis.
AB  - G protein-coupled receptors (GPCRs) are integral to cellular function in nearly
      all physiologic and many pathologic processes. GPCR signaling represents an
      intricate balance between receptor activation, inactivation (desensitization,
      internalization and degradation) and resensitization (recycling and de novo
      synthesis). Complex formation between phosphorylated GPCRs, arrestins and an ever
      increasing number of effector molecules is known to regulate cellular function.
      Previous studies have demonstrated that, although N-formyl peptide receptor (FPR)
      internalization occurs in the absence of arrestins, FPR recycling is arrestin
      dependent. Furthermore, FPR stimulation in the absence of arrestins leads to
      receptor accumulation in perinuclear endosomes and apoptosis. In this study, we
      show that the interaction of GPCR-bound arrestin with adaptor protein-2 (AP-2) is
      a critical anti-apoptotic event. In addition, AP-2 associates with the receptor
      arrestin complex in perinuclear endosomes and is required for proper post
      endocytic GPCR trafficking. Finally, we observed that depletion of endogenous AP
      2 results in the initiation of apoptosis upon stimulation of multiple GPCRs,
      including P2Y purinergic receptors and CXCR2, but not CXCR4. We propose a model
      in which the abnormal accumulation of internalized GPCR-arrestin complexes in
      recycling endosomes, resulting from defective arrestin-AP-2 interactions, leads
      to the specific initiation of aberrant signaling pathways and apoptosis.

PMID- 19602209
TI  - Does red blood cell storage affect clinical outcome? When in doubt, do the
      experiment.

PMID- 19602211
TI  - Stored platelet concentrates produced by the platelet-rich plasma method are more
      resistant to apoptosis but more sensitive to activation than are platelets
      prepared by the buffy-coat and apheresis methods.

PMID- 19602210
TI  - Therapeutic plasma exchange reveals a color-coordinated response to cyclosporine
      induced microangiopathic hemolytic anemia and rifampin after stem cell
      transplant.

PMID- 19602212
TI  - Effectiveness of various minipool nucleic acid test systems for hepatitis B virus
      detection in blood donors.

PMID- 19602213
TI  - Expected value of perfect information: an empirical example of reducing decision
      uncertainty by conducting additional research.
AB  - OBJECTIVE: Value of information (VOI) analysis informs decision-makers about the
      expected value of conducting more research to support a decision. This expected
      value of (partial) perfect information (EV(P)PI) can be estimated by
      simultaneously eliminating uncertainty on all (or some) parameters involved in
      model-based decision-making. This study aimed to calculate the EVPPI, before and
      after collecting additional information on the parameter of a probabilistic
      Markov model with the highest EVPPI. METHODS: The model assessed the 5-year costs
      per quality-adjusted life year (QALY) of three bronchodilators in chronic
      obstructive pulmonary disease (COPD). It had identified tiotropium as the
      bronchodilator with the highest expected net benefit. Total EVPI was estimated
      plus the EVPPIs for four groups of parameters: 1) transition probabilities
      between COPD severity stages; 2) exacerbation probabilities; 3) utility weights;
      and 4) costs. Partial EVPI analyses were performed using one-level and two-level
      sampling algorithms. RESULTS: Before additional research, the total EVPI was Euro
      1985 per patient at a threshold value of Euro 20,000 per QALY. EVPPIs were Euro
      1081 for utilities, Euro 724 for transition probabilities, and relatively small
      for exacerbation probabilities and costs. A large study was performed to obtain
      more precise EQ-5D utilities by COPD severity stages. After using posterior
      utilities, the EVPPI for utilities decreased to almost zero. The total EVPI for
      the updated model was reduced to Euro 1037. With an EVPPI of Euro 856, transition
      probabilities were now the single most important parameter contributing to the
      EVPI. CONCLUSIONS: This VOI analysis clearly identified parameters for which
      additional research is most worthwhile. After conducting additional research on
      the most important parameter, i.e., the utilities, total EVPI was substantially
      reduced.

PMID- 19602214
TI  - Balancing equity and efficiency in health priorities in Ghana: the use of
      multicriteria decision analysis.
AB  - OBJECTIVES: To guide the Ministry of Health in Ghana in the priority setting of
      interventions by quantifying the trade-off between equity, efficiency, and other
      societal concerns in health. METHODS: The study applied a multicriteria decision
      analytical framework. A focus group of seven policymakers identified the relevant
      criteria for priority setting and 63 policymakers participated in a discrete
      choice experiment to weigh their relative importance. Regression analysis was
      used to rank order a set of health interventions on the basis of these criteria
      and associated weights. RESULTS: Policymakers in Ghana consider targeting of
      vulnerable populations and cost-effectiveness as the most important criteria for
      priority setting of interventions, followed by severity of disease, number of
      beneficiaries, and diseases of the poor. This translates into a general
      preference for interventions in child health, reproductive health, and
      communicable diseases. CONCLUSION: Study results correspond with the overall
      vision of the Ministry of Health in Ghana, and are instrumental in the assessment
      of present and future investments in health. Multicriteria decision analysis
      contributes to transparency and accountability in policymaking.

PMID- 19602215
TI  - Cost-effectiveness of preventing hip fractures by hip protectors in elderly
      institutionalized residents in Germany.
AB  - OBJECTIVE: To determine the long-term cost-effectiveness of hip protector use in
      the prevention of hip fractures in elderly institutionalized residents in Germany
      compared to no prevention. METHODS: A lifetime Markov decision model was
      developed using published data on costs and health outcomes. A societal and
      statutory health insurance perspective was adopted. RESULTS: From a
      societal/statutory health insurance perspective, use of hip protectors yields
      savings of 315 EURO/257 EURO and a gain of 0.13 quality-adjusted life years per
      person over lifetime. CONCLUSION: Hip protector use in elderly institutionalized
      residents in Germany is highly cost-effective.

PMID- 19602216
TI  - Health state utility scores for cancer-related anemia through societal and
      patient valuations.
AB  - OBJECTIVES: Fatigue is recognized as the most serious complication of
      chemotherapy for the majority of patients. This study aims to determine
      preferences and utility values for health state descriptions of anemia associated
      with cancer treatment. METHODS: FACT-An clinical trial data were summarized to
      define health states associated with hemoglobin levels of 7.0-8.0, 8.0-9.0, 9.0
      10.0, 10.0-10.5, 10.5-11.0, 11.0-12.0, and 12.0+ g/dL. Health state descriptions
      were reviewed by clinicians and two quality-of-life experts. Eighty-five members
      of the general public were asked to rate the health states using a visual
      analogue scale and standard gamble (SG). Twenty-six oncology patients were
      interviewed using the time trade-off (TTO). RESULTS: The mean societal SG derived
      utility values showed a significant linear change from 0.583 +/- 0.067 (7-8 g/dL
      hemoglobin [Hb]) to 0.708 +/- 0.057 (12+ g/dL Hb). The patient TTO data ranged
      from 0.297 +/- 0.127 (7-8 g/dL Hb) to 0.611 +/- 0.092 (12+ g/dL Hb). CONCLUSIONS:
      The health state utility scores from both groups show a decrement in line with
      worsening anemia. Furthermore, patients who have experienced cancer-related
      fatigue rate the more severe levels of anemia much lower than the general public.

PMID- 19602217
TI  - Stroma-free mass production of clinical-grade red blood cells (RBCs) by using
      poloxamer 188 as an RBC survival enhancer.
AB  - BACKGROUND: In vitro generation of red blood cells (RBCs) is an important
      alternative to donor RBCs. It was impossible, however, to generate a large
      quantity of RBCs due to necessity of supporting stromal cells or xenogeneic or
      human serum for in vitro culture, which had restrictions in safety, supplies, and
      expenses. In addition, the low viability of erythroblasts during terminal
      maturation in vitro required highly efficient production protocols. Here, we
      present a protocol for mass production of clinical-grade RBCs from cord blood
      (CB) CD34+ cells in stroma-free culture by using poloxamer 188 (P188), a polymer
      known to be cytoprotective against hydrodynamic stress. STUDY DESIGN AND METHODS:
      Umbilical CB CD34+ cells were cultured for 21 days in medium containing several
      cytokines, and roughly fibrin-eliminated CB derived plasma was added from Day 13.
      To enhance the final RBC production, P188 was added from Day 13 and the cell
      count and viability were compared with controls lacking P188. RESULTS: Erythroid
      expansion between Day 17 and Day 21 was significantly higher in cultures treated
      with P188, with a mean of 1.5 times and maximum of 3.6 times higher expansion
      than in controls lacking P188. The enhanced survival resulted from increased
      stability of the RBC membrane and decreased fragility. The erythroid cells were
      enucleated up to 95% and demonstrated hematologic variables similar to those of
      reticulocytes. CONCLUSION: This RBC production protocol is a simple stroma- and
      serum-free culture method ensuring enhanced viability of terminally mature
      erythroid cells and can be easily applicable to mass production of clinical-grade
      RBCs as well as erythropoiesis research.

PMID- 19602218
TI  - The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project
      Study: protocol for a randomised controlled trial comparing methadone and
      buprenorphine for opiate detoxification.
AB  - BACKGROUND: In the United Kingdom (UK), there is an extensive market for the
      class 'A' drug heroin and many heroin users spend time in prison. People addicted
      to heroin often require prescribed medication when attempting to cease their drug
      use. The most commonly used detoxification agents in UK prisons are currently
      buprenorphine and methadone, both are recommended by national clinical
      guidelines. However, these agents have never been compared for opiate
      detoxification in the prison estate and there is a general paucity of research
      evaluating the most effective treatment for opiate detoxification in prisons.
      This study seeks to address this paucity by evaluating the most routinely used
      interventions amongst drug users within UK prisons. METHODS/DESIGN: This study
      uses randomised controlled trial methodology to compare the open use of
      buprenorphine and methadone for opiate detoxification, given in the context of
      routine care, within three UK prisons. Prisoners who are eligible and give
      informed consent will be entered into the trial. The primary outcome will be
      abstinence status eight days after detoxification, as determined by a urine test.
      Secondary outcomes will be recorded during the detoxification and then at one,
      three and six months post-detoxification. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN58823759.

PMID- 19602219
TI  - Return-to-work of sick-listed workers without an employment contract--what works?
AB  - BACKGROUND: In the past decade flexible labour market arrangements have emerged
      as a significant change in the European Union labour market. Studies suggest that
      these new types of labour arrangements may be linked to ill health, an increased
      risk for work disability, and inadequate vocational rehabilitation. Therefore,
      the objectives of this study were: 1. to examine demographic characteristics of
      workers without an employment contract sick-listed for at least 13 weeks, 2. to
      describe the content and frequency of occupational health care (OHC)
      interventions for these sick-listed workers, and 3. to examine OHC interventions
      as possible determinants for return-to-work (RTW) of these workers. METHODS: A
      cohort of 1077 sick-listed workers without an employment contract were included
      at baseline, i.e. 13 weeks after reporting sick. Demographic variables were
      available at baseline. Measurement of cross-sectional data took place 4-6 months
      after inclusion. Primary outcome measures were: frequency of OHC interventions
      and RTW-rates. Measured confounding variables were: gender, age, type of worker
      (temporary agency worker, unemployed worker, or remaining worker without
      employment contract), level of education, reason for absenteeism (diagnosis), and
      perceived health. The association between OHC interventions and RTW was analysed
      with a logistic multiple regression analysis. RESULTS: At 7-9 months after the
      first day of reporting sick only 19% of the workers had (partially or completely)
      returned to work, and most workers perceived their health as fairly poor or poor.
      The most frequently reported (49%) intervention was 'the OHC professional
      discussed RTW'. However, the intervention 'OHC professional made and discussed a
      RTW action plan' was reported by only 19% of the respondents. The logistic
      multiple regression analysis showed a significant positive association between
      RTW and the interventions: 'OHC professional discussed RTW'; and 'OHC
      professional made and discussed a RTW action plan'. The intervention 'OHC
      professional referred sick-listed worker to a vocational rehabilitation agency'
      was significantly associated with no RTW. CONCLUSION: This is the first time that
      characteristics of a large cohort of sick-listed workers without an employment
      contract were examined. An experimental or prospective study is needed to explore
      the causal nature of the associations found between OHC interventions and RTW.

PMID- 19602220
TI  - Treating 4,000 diabetic patients in Cambodia, a high-prevalence but resource
      limited setting: a 5-year study.
AB  - BACKGROUND: Despite the worldwide increasing burden of diabetes, there has been
      no corresponding scale-up of treatment in developing countries and limited
      evidence of program effectiveness. In 2002, in collaboration with the Ministry of
      Health of Cambodia, Medecins Sans Frontieres initiated an outpatient program of
      subsidized diabetic care in two hospital-based chronic disease clinics in rural
      settings. We aimed to describe the outcomes of newly and previously diagnosed
      diabetic patients enrolled from 2002 to 2008. METHODS: We calculated the mean and
      proportion of patients who met the recommended treatment targets, and the drop
      from baseline values for random blood glucose (RBG), hemoglobin A1c (HbA1c),
      blood pressure (BP), and body mass index (BMI) at regular intervals. Analysis was
      restricted to patients not lost to follow-up. We used the t test to compare
      baseline and subsequent paired values. RESULTS: Of 4404 patients enrolled, 2,872
      (65%) were still in care at the time of the study, 24 (0.5%) had died, and 1,508
      (34%) were lost to follow-up. Median age was 53 years, 2,905 (66%) were female
      and 4,350 (99%) had type 2 diabetes. Median (interquartile range (IQR)) follow-up
      was 20 months (5 to 39.5 months). A total of 24% (51/210) of patients had a HbA1c
      concentration of <7% and 35% (709/1,995) had a RBG <145 mg/dl within 1 year.
      There was a significant drop of 109 mg/dl (95% confidence interval (CI) 103.1 to
      114.3) in mean RBG (P < 0.001) and a drop of 2.7% (95% CI 2.3 to 3.0) in mean
      HbA1c (P < 0.001) between baseline and month 6. In all, 45% (327/723) and 62%
      (373/605) of patients with systolic or diastolic hypertension at baseline,
      respectively, reached = 130/80 mm Hg within 1 year. There was a drop of 13.5 mm
      Hg (95% CI 12.1 to 14.9) in mean systolic blood pressure (SBP) (P < 0.001), and a
      drop of 11.7 mm Hg (95% CI 10.8 to 12.6) in mean diastolic blood pressure (DBP)
      (P < 0.001) between baseline and month 6. Only 22% (90/401) patients with obesity
      at baseline lowered their BMI <27.5 kg/m2 after 1 year. Factors associated with
      loss to follow-up were male sex, age >60 years, living outside the province,
      normal BMI on admission, high RBG on last visit, and coming late for the last
      consultation. CONCLUSION: Significant and clinically important improvements in
      glycemia and BP were observed, but a relatively low proportion of diabetic
      patients reached treatment targets. These results and the high loss to follow-up
      rate highlight the challenges of delivering diabetic care in rural, resource
      limited settings.

PMID- 19602221
TI  - The consumption of Internet child pornography and violent and sex offending.
AB  - BACKGROUND: There is an ongoing debate on whether consumers of child pornography
      pose a risk for hands-on sex offenses. Up until now, there have been very few
      studies which have analyzed the association between the consumption of child
      pornography and the subsequent perpetration of hands-on sex offenses. The aim of
      this study was to examine the recidivism rates for hands-on and hands-off sex
      offenses in a sample of child pornography users using a 6 year follow-up design.
      METHODS: The current study population consisted of 231 men, who were subsequently
      charged with consumption of illegal pornographic material after being detected by
      a special operation against Internet child pornography, conducted by the Swiss
      police in 2002. Criminal history, as well as recidivism, was assessed using the
      criminal records from 2008. RESULTS: 4.8% (n = 11) of the study sample had a
      prior conviction for a sexual and/or violent offense, 1% (n = 2) for a hands-on
      sex offense, involving child sexual abuse, 3.3% (n = 8) for a hands-off sex
      offense and one for a nonsexual violent offense. When applying a broad definition
      of recidivism, which included ongoing investigations, charges and convictions, 3%
      (n = 7) of the study sample recidivated with a violent and/or sex offense, 3.9%
      (n = 9) with a hands-off sex offense and 0.8% (n = 2) with a hands-on sex
      offense. CONCLUSION: Consuming child pornography alone is not a risk factor for
      committing hands-on sex offenses - at least not for those subjects who had never
      committed a hands-on sex offense. The majority of the investigated consumers had
      no previous convictions for hands-on sex offenses. For those offenders, the
      prognosis for hands-on sex offenses, as well as for recidivism with child
      pornography, is favorable.

PMID- 19602223
TI  - Association between a rare SNP in the second intron of human Agouti related
      protein gene and increased BMI.
AB  - BACKGROUND: The agouti related protein (AGRP) is an endogenous antagonist of the
      melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim
      of the present study was to assess the genetic variability of AGRP gene and
      investigate whether the previously reported SNP rs5030980 and the rs11575892, a
      SNP that so far has not been studied with respect to obesity is associated with
      increased body mass index (BMI). METHODS: We determined the complete sequence of
      the AGRP gene and upstream promoter region in 95 patients with severe obesity
      (BMI > 35 kg/m2). Three polymorphisms were identified: silent mutation c.123G>A
      (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and
      c.131-42C>T (rs11575892) located in the second intron. We further screened
      rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants
      from the Genome Database of Latvian Population and Latvian State Research Program
      Database. RESULTS: The CT heterozygotes of rs11575892 had significantly higher
      mean BMI value (p = 0.027). After adjustment for age, gender and other
      significant non-genetic factors (presence of diseases), the BMI levels remained
      significantly higher in carriers of the rs11575892 T allele (p = 0.001). The
      adjusted mean BMI value of CC genotype was 27.92 +/- 1.01 kg/m2 (mean, SE) as
      compared to 30.97 +/- 1.03 kg/m2 for the CT genotype. No association was found
      between rs5030980 and BMI. CONCLUSION: This study presents an association of rare
      allele of AGRP polymorphism in heterozygous state with increased BMI. The
      possible functional effects of this polymorphism are unclear but may relate to
      splicing defects.

PMID- 19602222
TI  - Tolerability of inhaled N-chlorotaurine in the pig model.
AB  - BACKGROUND: N-chlorotaurine, a long-lived oxidant produced by human leukocytes,
      can be applied in human medicine as an endogenous antiseptic. Its antimicrobial
      activity can be enhanced by ammonium chloride. This study was designed to
      evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.
      METHODS: Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5%
      NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH4Cl) (n = 6), and 0.9% saline
      solution as a control (n = 7), respectively. Applications with 5 ml each were
      performed hourly within four hours. Lung function, haemodynamics, and
      pharmacokinetics were monitored. Bronchial lavage samples for captive bubble
      surfactometry and lung samples for histology and electron microscopy were
      removed. RESULTS: Arterial pressure of oxygen (PaO2) decreased significantly over
      the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1%
      NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 +/
      9.6 mmHg vs. 76 +/- 9.2 mmHg, p = 0.014) with a corresponding increase in
      alveolo-arterial difference of oxygen partial pressure (AaDO2) (p = 0.004).
      Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p =
      0.016). The increase of pulmonary artery pressure (PAP) over the observation
      period was smallest with 1% NCT without difference to controls (p = 0.91), and
      higher with 5% NCT (p = 0.02), and NCT + NH4Cl (p = 0.05).Histological and
      ultrastructural investigations revealed no differences between the test and
      control groups. The surfactant function remained intact. There was no systemic
      resorption of NCT detectable, and its local inactivation took place within 30
      min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro
      was similar to that known from other body cells (0.25-0.5 mM). CONCLUSION: The
      endogenous antiseptic NCT was well tolerated at a concentration of 1% upon
      inhalation in the pig model. Addition of ammonium chloride in high concentration
      provokes a statistically significant impact on blood oxygenation.

PMID- 19602224
TI  - Selection and validation of a set of reliable reference genes for quantitative RT
      PCR studies in the brain of the Cephalopod Mollusc Octopus vulgaris.
AB  - BACKGROUND: Quantitative real-time polymerase chain reaction (RT-qPCR) is
      valuable for studying the molecular events underlying physiological and
      behavioral phenomena. Normalization of real-time PCR data is critical for a
      reliable mRNA quantification. Here we identify reference genes to be utilized in
      RT-qPCR experiments to normalize and monitor the expression of target genes in
      the brain of the cephalopod mollusc Octopus vulgaris, an invertebrate. Such an
      approach is novel for this taxon and of advantage in future experiments given the
      complexity of the behavioral repertoire of this species when compared with its
      relatively simple neural organization. RESULTS: We chose 16S, and 18S rRNA, actB,
      EEF1A, tubA and ubi as candidate reference genes (housekeeping genes, HKG). The
      expression of 16S and 18S was highly variable and did not meet the requirements
      of candidate HKG. The expression of the other genes was almost stable and uniform
      among samples. We analyzed the expression of HKG into two different set of
      animals using tissues taken from the central nervous system (brain parts) and
      mantle (here considered as control tissue) by BestKeeper, geNorm and NormFinder.
      We found that HKG expressions differed considerably with respect to brain area
      and octopus samples in an HKG-specific manner. However, when the mantle is
      treated as control tissue and the entire central nervous system is considered,
      NormFinder revealed tubA and ubi as the most suitable HKG pair. These two genes
      were utilized to evaluate the relative expression of the genes FoxP, creb, dat
      and TH in O. vulgaris. CONCLUSION: We analyzed the expression profiles of some
      genes here identified for O. vulgaris by applying RT-qPCR analysis for the first
      time in cephalopods. We validated candidate reference genes and found the
      expression of ubi and tubA to be the most appropriate to evaluate the expression
      of target genes in the brain of different octopuses. Our results also underline
      the importance of choosing a proper normalization strategy when analyzing gene
      expression by qPCR taking into appropriate account the experimental setting and
      variability of the sample of animals (and tissues), thus providing a set of HGK
      which expression appears to be unaffected by the experimental factor(s).

PMID- 19602225
TI  - Pedestrian injury and the built environment: an environmental scan of hotspots.
AB  - BACKGROUND: Pedestrian injury frequently results in devastating and costly
      injuries and accounts for 11% of all road user fatalities. In the United States
      in 2006 there were 4,784 fatalities and 61,000 injuries from pedestrian injury,
      and in 2007 there were 4,654 fatalities and 70,000 injuries. In Canada, injury is
      the leading cause of death for those under 45 years of age and the fourth most
      common cause of death for all ages Traumatic pedestrian injury results in nearly
      4000 hospitalizations in Canada annually. These injuries result from the
      interplay of modifiable environmental factors. The objective of this study was to
      determine links between the built environment and pedestrian injury hotspots in
      Vancouver. METHODS: Data were obtained from the Insurance Corporation of British
      Columbia (ICBC) for the 6 year period from 2000 to 2005 and combined with
      pedestrian injury data extracted from the British Columbia Trauma Registry (BCTR)
      for the same period. High incident locations (hotspots) for pedestrian injury in
      the City of Vancouver were identified and mapped using geographic information
      systems (GIS), and the characteristics of the built environment at each of the
      hotspot locations were examined by a team of researchers. RESULTS: The analysis
      highlighted 32 pedestrian injury hotspot locations in Vancouver. 31 of 32
      hotspots were situated on major roads. Likewise, the majority of hotspots were
      located on downtown streets. The 'downtown eastside' was identified as an area
      with multiple high-incident locations, including the 2 highest ranked pedestrian
      injury hotspots. Bars were present at 21 of the hotspot locations, with 11 of
      these locations being judged to have high alcohol establishment density.
      CONCLUSION: This study highlighted the disproportionate burden of pedestrian
      injury centred on the downtown eastside area of Vancouver. The environmental scan
      revealed that important passive pedestrian safety countermeasures were only
      present at a minority of high-incident locations. More importantly, bars were
      highly associated with risk of pedestrian injury. This study is the basis for
      potential public health intervention by clearly indicating optimal locations for
      signalized pedestrian crosswalks.

PMID- 19602226
TI  - Evaluation of the medical student research programme in Norwegian medical
      schools. A survey of students and supervisors.
AB  - BACKGROUND: The Medical Student Research Programme is a national education and
      grant scheme for medical students who wish to carry out research in parallel with
      their studies. The purpose of the programme is to increase recruitment of people
      with a standard medical degree to medical research. The Research Programme was
      established in 2002 and underwent a thorough evaluation during the spring of
      2007. The evaluation should investigate if the programme had fulfilled its
      objectives of increased recruitment to medical research, in addition to the
      students' and supervisors' satisfaction of the programme, and unwanted
      differences between the universities. METHODS: Data was collected from students,
      supervisors and administrative staff via web-based questionnaires. Information
      about admission, implementation, results achieved and satisfaction was analysed
      and compared between the four Norwegian medical schools. In addition, the
      position of the scheme in relation to the national Quality Reform of Higher
      Education was analysed. RESULTS: At the end of 2006, the Medical Student Research
      Programme had recruited 265 medical students to research. These consisted of 214
      active students, 35 who had completed their studies and only 17 who had dropped
      out. Both students and supervisors were generally very satisfied with the scheme,
      including the curriculum, the results achieved and the administrative service.
      The majority of students wanted to continue their research towards a PhD and, of
      those who had completed the Medical Student Research Programme, practically all
      had published one or several scientific papers. The survey showed only small
      differences between the four medical schools, despite their choice of somewhat
      different solutions in terms of administration and organisation. The Medical
      Student Research Programme satisfies the majority of the demands of the Quality
      Reform, however as an integrated research programme aimed at a PhD it presupposes
      access to PhD courses before the completion of medical studies, as well as the
      ability to include undergraduate scientific work in a PhD thesis. CONCLUSION: The
      Medical Student Research Programme has led to an increase in the recruitment of
      graduated physicians to medical research in Norway. It will only be possible to
      evaluate whether this in turn will result in a larger number of PhDs in 3-5
      years; this will also depend on the access to grants and fellowships.

PMID- 19602227
TI  - Responding to chromosomal breakage during M-phase: insights from a cell-free
      system.
AB  - DNA double strand breaks (DSBs) activate ATM and ATR dependent checkpoints that
      prevent the onset of mitosis. However, how cells react to DSBs occurring when
      they are already in mitosis is poorly understood. The Xenopus egg extract has
      been utilized to study cell cycle progression and DNA damage checkpoints.
      Recently this system has been successfully used to uncover an ATM and ATR
      dependent checkpoint affecting centrosome driven spindle assembly. These studies
      have led to the identification of XCEP63 as major target of this pathway. XCEP63
      is a coiled-coil rich protein localized at centrosome essential for proper
      spindle assembly. ATM and ATR directly phosphorylate XCEP63 on serine 560
      inducing its delocalization from centrosome, which in turn delays spindle
      assembly. This pathway might contribute to regulate DNA repair or mitotic cell
      survival in the presence of chromosome breakage.

PMID- 19602228
TI  - Expression and function of proton-sensing G-protein-coupled receptors in
      inflammatory pain.
AB  - BACKGROUND: Chronic inflammatory pain, when not effectively treated, is a costly
      health problem and has a harmful effect on all aspects of health-related quality
      of life. Despite the availability of pharmacologic treatments, chronic
      inflammatory pain remains inadequately treated. Understanding the nociceptive
      signaling pathways of such pain is therefore important in developing long-acting
      treatments with limited side effects. High local proton concentrations (tissue
      acidosis) causing direct excitation or modulation of nociceptive sensory neurons
      by proton-sensing receptors are responsible for pain in some inflammatory pain
      conditions. We previously found that all four proton-sensing G-protein-coupled
      receptors (GPCRs) are expressed in pain-relevant loci (dorsal root ganglia, DRG),
      which suggests their possible involvement in nociception, but their functions in
      pain remain unclear. RESULTS: In this study, we first demonstrated differential
      change in expression of proton-sensing GPCRs in peripheral inflammation induced
      by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant
      (CFA). In particular, the expression of TDAG8, one proton-sensing GPCR, was
      increased 24 hours after CFA injection because of increased number of DRG neurons
      expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient
      receptor potential vanilloid 1 (TRPV1) was increased as well. Further studies
      revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin,
      suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain
      through regulation of TRPV1 function. CONCLUSION: Each subtype of the OGR1 family
      was expressed differently, which may reflect differences between models in
      duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression
      increased after CFA-induced inflammation and that TDAG8 activation can lead to
      TRPV1 sensitization, it suggests that high concentrations of protons after
      inflammation may not only directly activate proton-sensing ion channels (such as
      TRPV1) to cause pain but also act on proton-sensing GPCRs to regulate the
      development of hyperalgesia.

PMID- 19602229
TI  - The pattern of mucocutaneous disorders in HIV-infected children attending care
      and treatment centres in Dar es Salaam, Tanzania.
AB  - BACKGROUND: HIV/AIDS is associated with a wide range of mucocutaneous disorders
      some of which are useful in the clinical staging and prognosis of the syndrome.
      There is paucity of information regarding the prevalence and pattern of
      mucocutaneous disorders among HIV infected children attending paediatric Care and
      Treatment Centres (CTC) in Dar es Salaam. OBJECTIVE: To determine the prevalence
      and pattern of mucocutaneous disorders among HIV infected children attending
      public paediatric 'Care and Treatment Centres' in Dar es Salaam. METHODS: This
      was a cross sectional descriptive study involving public paediatric 'Care and
      Treatment Centres' in Dar es Salaam. Clinical information was obtained using a
      questionnaire. Dermatological examination was carried out in daylight.
      Investigations were taken as appropriate. Data was analysed using the Statistical
      Package for Social Sciences (SPSS) program version 10.0. Chi-squared and Fisher's
      exact tests were utilized. A p-value of less than 0.05 was considered
      statistically significant. RESULTS: Three hundred and forty seven HIV infected
      children (52% males) attending CTCs were recruited into the study. Mucocutaneous
      disorders were encountered in 85% of them. There was no gender difference in the
      prevalence of the infective mucocutaneous disorders but males had a higher
      prevalence of non-infective/inflammatory dermatoses (58%) than females (42%) (p =
      0.02). Overall, mucocutaneous disorders (infective + non infective) were more
      prevalent in advanced stages of HIV disease. Children with advanced HIV disease
      had a significantly increased frequency of fungal and viral infections (43% and
      25% respectively than those with less advanced disease; 24% and 13% respectively
      (p = 0.01). Seventy four percent of the HIV-infected children with mucocutaneous
      disorders were already on ART. CONCLUSION: Mucocutaneous disorders among HIV
      infected children attending Care and Treatment Centres are common and highly
      variable. Comprehensive management should also emphasize on the management of
      mucocutaneous disorders.

PMID- 19602230
TI  - Which theory is best? Explanatory models of the relationship between unemployment
      and health.
AB  - BACKGROUND: A number of different models have been used in order to explain the
      links between unemployment and ill-health. The objective of this study was to
      test different proposed models in an empirical setting. METHODS: A cohort of
      school-leavers consisting of more than 1000 persons was followed for 14 years up
      to the age of 30. They have repeatedly been asked questions that could be used to
      operationalise different proposed models as well as health outcomes. Seven
      different models explaining the health effect of unemployment were identified: an
      economic deprivation model, a lack of control model as well as a locus of control
      model, a stress model, a social support model, a work involvement model and a
      model of latent functions. Health outcomes used were somatic symptoms, depressive
      symptoms, self-perceived health and nervous problems. Statistical tests included
      bivariate correlations and logistic regression. RESULTS: Most of the models
      correlated fairly well with unemployment measures. The capacity of the models to
      explain the connection between unemployment and ill-health varied, however. The
      model of latent functions was most successful, followed by the economic
      deprivation model. The social support and the control models were also fairly
      good. The work involvement scale and the stress model demonstrated the smallest
      explanatory power. CONCLUSION: Studies comparing different explanatory models in
      the field are rare. Few models apply a multidisciplinary approach. In view of the
      findings, it should be possible to develop multidisciplinary and better models to
      explain the links between unemployment and health in more detail.

PMID- 19602231
TI  - Characteristics of equine summer eczema with emphasis on differences between
      Finnhorses and Icelandic horses in a 11-year study.
AB  - Summer eczema, allergic dermatitis of the horse, was studied on 275 affected
      horses in Finland in 1997-2007. Features of the horses, clinical signs of the
      disease and owners' opinions of aggravating factors were recorded. Differences,
      especially, between two of the native Scandinavian horse breeds, the Finnhorse
      and the Icelandic horse, were evaluated. The study was based on clinical
      examination and information from the owners. Of the horses, 50% were Finnhorses,
      26% Icelandic horses and 24% consisted of different breeds of ponies and other
      horses. Of the Finnhorses, 76% had summer eczema by the age of 5 years, but in
      the Icelandic horses born in Finland the average age at onset was 7 years. The
      vast majority of the horses, 75%, had moderate clinical signs, while 16% showed
      severe and 9% mild. The severity of clinical signs did not depend on the duration
      of the disease nor was it related to the age at onset. The only linkage to
      severity was the breed of the horse or import from Iceland; New Forest ponies and
      imported Icelandic horses showed severe clinical signs significantly more often
      than Finnhorses. Of the owners, 38% regarded insects as the only aggravating
      factor, 24% mentioned several simultaneous factors, including grass fodder and
      sunlight, while 22% could not specify any. In Finland, a typical horse breed
      suffering from summer eczema is the Finnhorse and the characteristics of the
      disease are mainly uniform with the other breeds affected. Equine summer eczema
      seems to be aggravated by various combinations of environmental factors.

PMID- 19602232
TI  - Identification of potential therapeutic targets in human head & neck squamous
      cell carcinoma.
AB  - BACKGROUND: Human head and neck squamous cell carcinoma (HNSCC) is an aggressive
      and recurrent malignancy. Identification of unique or overexpressed cell
      associated or cell surface antigens is critical for diagnosis and development of
      cancer vaccines and targeted therapies for HNSCC. We have used high throughput
      microarray technology to search for candidate targets in HNSCC. METHODS: Gene
      expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed
      by microarray. QRT-PCR analysis was performed to validate the microarray results.
      The five candidate genes were further characterized by immunohistochemical
      technique in surgical samples and tissue arrays. RESULTS: A total of 192 up
      regulated genes at statistical significance of p < 0.01 and log2 ratio > or = 1
      were identified in HNSCC tumors compared to normal tissues. These genes belong to
      immune response, cell growth, cell cycle regulation, oncogenes, metabolism and
      others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27)
      were identified, which were highly expressed in HNSCC tumor samples and tissue
      arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and
      FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC.
      CONCLUSION: Five genes and their products may serve as a diagnostic biomarker or
      therapeutic target for HNSCC. While additional work is needed to elucidate the
      biological significance of these proteins, CD24 and CD74 expressed only in small
      proportion of cells indicating tumor heterogeneity and subtypes of tumor
      initiating cells (CD24+/CD44+) present in HNSCC.

PMID- 19602234
TI  - The surged faradic stimulation to the pelvic floor muscles as an adjunct to the
      medical management in children with rectal prolapse.
AB  - BACKGROUND: To assess the role of the surged faradic stimulation to the pelvic
      floor muscles as an adjunct to the conservative management in the children of
      idiopathic rectal prolapse. METHODS:  STUDY DESIGN: Prospective. SETTING:
      Pediatric Surgery Department, Pt BD Sharma, Post Graduate Institute of Medical
      Sciences, Rohtak. SUBJECTS: 47 consecutive children with idiopathic rectal
      prolapse attending the Pediatric Surgery out patient department from July 2005 to
      June 2006. METHODOLOGY: The information pertaining to duration and the extent of
      rectal prolapse, predisposing or associated medical conditions, results of local
      clinical examination were noted. Surged faradic stimulation using modified
      intraluminal rectal probe, was given on the alternate days. The conventional
      conservative medical management was also continued. The extent of relief and the
      number of the sittings of faradic stimulation required were noted at various
      stages of follow-ups. STATISTICAL METHODS: Mean values between those completely
      cured and others; poor responders and others were compared with t-test and
      proportions were compared with Chi square test. The p-value < 0.05 was considered
      statistically significant. RESULTS: The mean number of sittings in the completely
      cured group (n = 28(64%)) was (12.4 +/- 7.8) and was comparable with very poor
      responder (n = 6(13%). There was higher percentage of relief (76%) at the first
      follow up (at 15 days) in completely cured Vs other (37%) and also the poor
      responders showed (20%) Vs other (68%) and was statistically significant.
      CONCLUSION: With use of faradic stimulation, even the long-standing rectal
      prolapse can be fully cured. The follow up visit at 2 weeks is very important to
      gauge the likely success of this modality in treatment of the patients with
      rectal prolapse. Those showing poor response at this stage may require
      alternative treatment or take a long time to get cured.

PMID- 19602233
TI  - The QICKD study protocol: a cluster randomised trial to compare quality
      improvement interventions to lower systolic BP in chronic kidney disease (CKD) in
      primary care.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a relatively newly recognised but
      common long-term condition affecting 5 to 10% of the population. Effective
      management of CKD, with emphasis on strict blood pressure (BP) control, reduces
      cardiovascular risk and slows the progression of CKD. There is currently an
      unprecedented rise in referral to specialist renal services, which are often
      located in tertiary centres, inconvenient for patients, and wasteful of
      resources. National and international CKD guidelines include quality targets for
      primary care. However, there have been no rigorous evaluations of strategies to
      implement these guidelines. This study aims to test whether quality improvement
      interventions improve primary care management of elevated BP in CKD, reduce
      cardiovascular risk, and slow renal disease progression DESIGN: Cluster
      randomised controlled trial (CRT) METHODS: This three-armed CRT compares two well
      established quality improvement interventions with usual practice. The two
      interventions comprise: provision of clinical practice guidelines with prompts
      and audit-based education. The study population will be all individuals with CKD
      from general practices in eight localities across England. Randomisation will
      take place at the level of the general practices. The intended sample (three arms
      of 25 practices) powers the study to detect a 3 mmHg difference in systolic BP
      between the different quality improvement interventions. An additional 10
      practices per arm will receive a questionnaire to measure any change in
      confidence in managing CKD. Follow up will take place over two years. Outcomes
      will be measured using anonymised routinely collected data extracted from
      practice computer systems. Our primary outcome measure will be reduction of
      systolic BP in people with CKD and hypertension at two years. Secondary outcomes
      will include biomedical outcomes and markers of quality, including practitioner
      confidence in managing CKD. A small group of practices (n = 4) will take part in
      an in-depth process evaluation. We will use time series data to examine the
      natural history of CKD in the community. Finally, we will conduct an economic
      evaluation based on a comparison of the cost effectiveness of each intervention.
      CLINICAL TRIALS REGISTRATION: ISRCTN56023731. ClinicalTrials.gov identifier.

PMID- 19602236
TI  - Bundling occupational safety with harm reduction information as a feasible method
      for improving police receptiveness to syringe access programs: evidence from
      three U.S. cities.
AB  - INTRODUCTION: In light of overwhelming evidence that access to sterile injection
      equipment reduces incidence of injection-attributable bloodborne disease without
      encouraging drug use, many localities have authorized sterile syringe access
      programs (SAPs), including syringe exchange and pharmacy-based initiatives. Even
      where such interventions are clearly legal, many law enforcement officers are
      unaware of the public health benefits and legal status of these programs and may
      continue to treat the possession of injection equipment as illegal and program
      participation as a marker of illegal behavior. Law enforcement practice can
      impede SAP utilization and may increase the risk of needlestick injury (NSI)
      among law enforcement personnel. Many SAPs conduct little or no outreach to law
      enforcement, in part because they perceive law enforcement actors as unreceptive
      to health-promotion programs targeting drug users. CASE DESCRIPTION: We report on
      a brief training intervention for law enforcement personnel designed to increase
      officer knowledge of and positive attitudes towards SAPs by bundling content that
      addresses officer concerns about infectious disease and occupational safety with
      information about the legality and public health benefits of these programs.
      Pilot trainings using this bundled curriculum were conducted with approximately
      600 officers in three US cities. DISCUSSION AND EVALUATION: Law enforcement
      officers were generally receptive to receiving information about SAPs through the
      bundled curriculum. The trainings led to better communication and collaboration
      between SAP and law enforcement personnel, providing a valuable platform for
      better harmonization of law enforcement and public health activities targeting
      injection drug users. CONCLUSION: The experience in these three cities suggests
      that a harm reduction training curriculum that bundles strategies for increasing
      officer occupational safety with information about the legality and public health
      benefits of SAPs can be well received by law enforcement personnel and can lead
      to better communication and collaboration between law enforcement and harm
      reduction actors. Further study is indicated to assess whether such a bundled
      curriculum is effective in changing officer attitudes and beliefs and reducing
      health risks to officers and injection drug users, as well as broader benefits to
      the community at large.

PMID- 19602235
TI  - MHC-linked and un-linked class I genes in the wallaby.
AB  - BACKGROUND: MHC class I antigens are encoded by a rapidly evolving gene family
      comprising classical and non-classical genes that are found in all vertebrates
      and involved in diverse immune functions. However, there is a fundamental
      difference between the organization of class I genes in mammals and non-mammals.
      Non-mammals have a single classical gene responsible for antigen presentation,
      which is linked to the antigen processing genes, including TAP. This organization
      allows co-evolution of advantageous class Ia/TAP haplotypes. In contrast, mammals
      have multiple classical genes within the MHC, which are separated from the
      antigen processing genes by class III genes. It has been hypothesized that
      separation of classical class I genes from antigen processing genes in mammals
      allowed them to duplicate. We investigated this hypothesis by characterizing the
      class I genes of the tammar wallaby, a model marsupial that has a novel MHC
      organization, with class I genes located within the MHC and 10 other chromosomal
      locations. RESULTS: Sequence analysis of 14 BACs containing 15 class I genes
      revealed that nine class I genes, including one to three classical class I, are
      not linked to the MHC but are scattered throughout the genome. Kangaroo
      Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class
      I. The wallaby MHC contains four non-classical class I, interspersed with antigen
      processing genes. Clear orthologs of non-classical class I are conserved in
      distant marsupial lineages. CONCLUSION: We demonstrate that classical class I
      genes are not linked to antigen processing genes in the wallaby and provide
      evidence that retroviral elements were involved in their movement. The presence
      of retroviral elements most likely facilitated the formation of recombination
      hotspots and subsequent diversification of class I genes. The classical class I
      have moved away from antigen processing genes in eutherian mammals and the
      wallaby independently, but both lineages appear to have benefited from this loss
      of linkage by increasing the number of classical genes, perhaps enabling response
      to a wider range of pathogens. The discovery of non-classical orthologs between
      distantly related marsupial species is unusual for the rapidly evolving class I
      genes and may indicate an important marsupial specific function.

PMID- 19602237
TI  - RIZ1 is potential CML tumor suppressor that is down-regulated during disease
      progression.
AB  - BACKGROUND: RIZ1 expression and activity are reduced in many cancers. In AML cell
      lines and patient material, RIZ1 expression is reduced relative to normal bone
      marrow. In chronic myelogenous leukemia (CML), blastic transformation is
      associated with loss of heterozygosity in the region where RIZ1 is located. RIZ1
      is a PR domain methyltransferase that methylates histone H3 lysine 9, a
      modification important for transcriptional repression. In CML blast crisis cell
      lines RIZ1 represses insulin-like growth factor-1 expression and autocrine
      signaling. Together these observations suggest that RIZ1 may have a role in the
      chronic phase to blast crisis transition in CML. RESULTS: In CML patient
      material, we observed that RIZ1 expression was decreased during progression from
      chronic phase to blast crisis. RIZ1 was expressed in mature myeloid and CD34+
      cells demonstrating that decreased RIZ1 expression in blast crisis is not due to
      an increased immature cell population. Expression of RIZ1 CML blast crisis cell
      lines decreased proliferation, increased apoptosis, and enhanced differentiation.
      CONCLUSION: RIZ1 is a candidate tumor suppressor gene whose expression is
      decreased in blast crisis. Loss of RIZ1 activity results in decreased apoptosis
      and differentiation and enhanced proliferation. Together these results suggest
      that loss of RIZ1 expression will lead to an increase in myeloid blast cell
      population resulting in CML progression.

PMID- 19602239
TI  - Comparing public-health research priorities in Europe.
AB  - BACKGROUND: Despite improving trends, countries in Europe continue to face public
      health challenges. This study investigated the priorities of stakeholders for
      research to meet these challenges. METHODS: Public-health research includes
      population-level and health-system research, but not clinical or biomedical
      research. The study drew on data from three surveys undertaken through
      collaboration in SPHERE (Strengthening Public Health Research in Europe). There
      was participation of ministries in 18 of 28 (64% response) European countries,
      from 22 of 39 (56% response) member national associations of the European Public
      Health Association, and from 80 civil society health organisations (53% of
      members of the European Public Health Alliance) RESULTS: Public-health research
      fields included disease control, health promotion and health services. Ministries
      of health, rather than ministries of science or education, mostly took
      responsibility for public-health research: they reported varied but well-defined
      areas for research in relation to national health plans and programmes. National
      public health associations reported research priorities across most fields of
      public health, although with some European regional differences. Civil society
      health organisations prioritised health promotion research nationally, but also
      health services research internationally. There was less research reported on
      methods, such as modelling and economic analysis, wider determinants of health,
      and public-health interventions. CONCLUSION: Systematic collaboration between
      stakeholders across European countries would enhance knowledge and promote
      innovation to address contemporary public-health challenges.

PMID- 19602238
TI  - IL-13 expression by blood T cells and not eosinophils is increased in asthma
      compared to non-asthmatic eosinophilic bronchitis.
AB  - BACKGROUND: In asthma interleukin (IL)-13 is increased in the airway compared
      with non-asthmatic eosinophilic bronchitis. Whether this differential expression
      is specific to the airway or is more generalised is uncertain. METHODS: We sought
      to examine IL-13 expression in peripheral blood T-cells and eosinophils in asthma
      and non-asthmatic eosinophilic bronchitis. Peripheral blood CD3+ cell and
      eosinophil intracellular IL-13 expression from subjects with asthma, non
      asthmatic eosinophilic bronchitis and healthy controls was assessed. The effect
      of priming by asthmatic serum on the release of IL-13 by peripheral blood
      mononuclear cells from healthy subjects was examined and the serum from these
      subjects was analysed for a range of chemokines and cytokines. RESULTS: The
      median (IQR)% intracellular IL-13 expression by CD3+ cells was increased in
      asthma [5.3 (2.7-9.8)%; n = 12] compared to non-asthmatic eosinophilic bronchitis
      [1.1 (0.5-3)%; n = 7] and healthy controls [1.7 (0.2-3%); n = 9] (p = 0.02), but
      was not significantly different in eosinophils across the groups. IL-13 released
      from healthy peripheral blood mononuclear cells (n = 10) was increased by
      asthmatic serum [117 (47.8-198)pg/ml] compared to control [78.5 (42.6-128)pg/ml;
      p = 0.02), but was not affected by non-asthmatic serum. CONCLUSION: Our findings
      support the view that IL-13 expression is increased in peripheral blood-derived T
      cells in asthma and that asthmatic serum up-regulates IL-13 release from healthy
      peripheral blood mononuclear cells.

PMID- 19602240
TI  - Immunohistochemical study of the phenotypic change of the mesenchymal cells
      during portal tract maturation in normal and fibrous (ductal plate malformation)
      fetal liver.
AB  - BACKGROUND: In adult liver, the mesenchymal cells, portal fibroblasts and
      vascular smooth muscle cells can transdifferentiate into myofibroblasts, and are
      involved in portal fibrosis. Differential expression of markers, such as alpha
      smooth muscle actin (ASMA), h-caldesmon and cellular retinol-binding protein-1
      allows their phenotypic discrimination. The aim of our study was to explore the
      phenotypic evolution of the mesenchymal cells during fetal development in normal
      liver and in liver with portal fibrosis secondary to ductal plate malformation in
      a series of Meckel-Gruber syndrome, autosomal recessive polycystic kidney disease
      and Ivemark's syndrome. RESULTS: At the early steps of the portal tract
      maturation, portal mesenchymal cells expressed only ASMA. During the maturation
      process, these cells were found condensed around the biliary and vascular
      structures. At the end of maturation process, only cells around vessels expressed
      ASMA and cells of the artery tunica media also expressed h-caldesmon. In
      contrast, ASMA positive cells persisted around the abnormal biliary ducts in
      fibrous livers. CONCLUSION: As in adult liver, there is a phenotypic
      heterogeneity of the mesenchymal cells during fetal liver development. During
      portal tract maturation, myofibroblastic cells disappear in normal development
      but persist in fibrosis following ductal plate malformation.

PMID- 19602241
TI  - Genetic diversity and population structure of Plasmodium falciparum in Thailand,
      a low transmission country.
AB  - BACKGROUND: The population structure of the causative agents of human malaria,
      Plasmodium sp., including the most serious agent Plasmodium falciparum, depends
      on the local epidemiological and demographic situations, such as the incidence of
      infected people, the vector transmission intensity and migration of inhabitants
      (i.e. exchange between sites). Analysing the structure of P. falciparum
      populations at a large scale, such as continents, or with markers that are
      subject to non-neutral selection, can lead to a masking and misunderstanding of
      the effective process of transmission. Thus, knowledge of the genetic structure
      and organization of P. falciparum populations in a particular area with neutral
      genetic markers is needed to understand which epidemiological factors should be
      targeted for disease control. Limited reports are available on the population
      genetic diversity and structure of P. falciparum in Thailand, and this is of
      particular concern at the Thai-Myanmar and Thai-Cambodian borders, where there is
      a reported high resistance to anti-malarial drugs, for example mefloquine, with
      little understanding of its potential gene flow. METHODS: The diversity and
      genetic differentiation of P. falciparum populations were analysed using 12
      polymorphic apparently neutral microsatellite loci distributed on eight of the 14
      different chromosomes. Samples were collected from seven provinces in the
      western, eastern and southern parts of Thailand. RESULTS: A strong difference in
      the nuclear genetic structure was observed between most of the assayed
      populations. The genetic diversity was comparable to the intermediate level
      observed in low P. falciparum transmission areas (average HS = 0.65 +/- 0.17),
      where the lowest is observed in South America and the highest in Africa. However,
      uniquely the Yala province, had only a single multilocus genotype present in all
      samples, leading to a strong geographic differentiation when compared to the
      other Thai populations during this study. Comparison of the genetic structure of
      P. falciparum populations in Thailand with those in the French Guyana, Congo and
      Cameroon revealed a significant genetic differentiation between all of them,
      except the two African countries, whilst the genetic variability of P. falciparum
      amongst countries showed overlapping distributions. CONCLUSION: Plasmodium
      falciparum shows genetically structured populations across local areas of
      Thailand. Although Thailand is considered to be a low transmission area, a
      relatively high level of genetic diversity and no linkage disequilibrium was
      found in five of the studied areas, the exception being the Yala province
      (Southern peninsular Thailand), where a clonal population structure was revealed
      and in Kanchanaburi province (Western Thailand). This finding is particularly
      relevant in the context of malaria control, because it could help in
      understanding the special dynamics of parasite populations in areas with
      different histories of, and exposure to, drug regimens.

PMID- 19602242
TI  - Certification of breast centres in Germany: proof of concept for a prototypical
      example of quality assurance in multidisciplinary cancer care.
AB  - BACKGROUND: The main study objectives were: to develop a set of requirements of
      comprehensive breast centres; to establish a nationwide voluntary certification
      programme for breast centres based on such requirements, a certified quality
      management system (QMS), and scheduled independent, external audits and periodic
      recertification; and to demonstrate the general acceptance of such a
      certification programme with a view to introducing similar certification
      programmes for other major cancers. METHODS: Breast centres introduced a QMS and
      voluntarily participated in an external certification procedure based on
      guideline-derived Requirements of Breast Centres specifically developed for the
      application procedure, all subsequent audits and recertification. All data
      (numbers of pending and successful applications, sites/centre, etc.) were
      collected by a newly founded, independent organisation for certification of
      cancer services delivery. Data analysis was descriptive. RESULTS: Requirements of
      Breast Centres were developed by the German Cancer Society (DKG), the German
      Society of Senology (DGS) and other relevant specialist medical societies in the
      form of a questionnaire comprising 185 essential items based on evidence-based
      guidelines and the European Society of Breast Cancer Specialists' (EUSOMA)
      requirements of specialist breast units. From late 2002 to mid 2008, the number
      of participating breast centres rose from 1 to 175. As of mid 2008, 77% of an
      estimated 50,000 new breast cancers in Germany were diagnosed and treated at
      certified breast centres, 78% of which were single-site centres. CONCLUSION:
      Nationwide voluntary certification of breast centres is feasible and well
      accepted in Germany. Dual certification of breast centres that involves
      certification of breast services to guideline-derived requirements in conjunction
      with independent certification of a mandatory QMS can serve as a model for other
      multidisciplinary site-specific cancer centres.

PMID- 19602243
TI  - Suppressive response of confections containing the extractive from leaves of
      Morus Alba on postprandial blood glucose and insulin in healthy human subjects.
AB  - BACKGROUND: The first aim of this study was to clarify the effective ratio of
      extractive from leaves of Morus Alba (ELM) to sucrose so as to apply this
      knowledge to the preparation of confections that could effectively suppress the
      elevation of postprandial blood glucose and insulin. The second aim was to
      identify the efficacy of confections prepared with the optimally effective ratio
      determined from the first study, using healthy human subjects. METHODS: Ten
      healthy females (22.3 years, BMI 21.4 kg/m2) participated in this within-subject,
      repeated measures study. For the first aim of this study, the test solutions
      containing 30 g of sucrose and 1.2 or 3.0 g of ELM were repeatedly and randomly
      given to each subject. To identify the practically suppressive effects on
      postprandial blood glucose and insulin, some confections with added ELM were
      prepared as follows: Mizu-yokan, 30 g of sucrose with the addition of 1.5 or 3.0
      g ELM; Daifuku-mochi, 9.0 g of starch in addition to 30 g of sucrose and 1.5 or
      3.0 g ELM; Chiffon-cake, 24 g of sucrose, starch, and 3.0 or 6.0 g of ELM, and
      were ingested by each subject. Blood and end-expiration were collected at
      selected periods after test food ingestion. RESULTS: When 30 g of sucrose with
      1.2 or 3.0 g of ELM were ingested by subjects, the elevations of postprandial
      blood glucose and insulin were effectively suppressed (p < 0.01), and the most
      effective ratio of ELM to sucrose was evaluated to be 1:10. AUC (area under the
      curve) of breath hydrogen excretion for 6 h after the ingestion of an added 3 g
      of ELM significantly increased (p < 0.01). When AUCs-3h of incremental blood
      glucose of confections without ELM was 100, that of Mizu-yokan and Daifuku-mochi
      with the ratio (1:10) of ELM to sucrose was decreased to 53.4 and 58.2,
      respectively. Chiffon-cake added one-fourth ELM was 29.0. CONCLUSION: ELM
      containing confections for which the ratio of ELM and sucrose is one-tenth
      effectively suppress the postprandial blood glucose and insulin by inhibiting the
      intestinal sucrase, thus creating a prebiotic effect. The development of
      confections with ELM can therefore contribute to the prevention and the quality
      of life for prediabetic and diabetic patients.

PMID- 19602245
TI  - Challenging for cartilage repair.

PMID- 19602244
TI  - Community perceptions and factors influencing utilization of health services in
      Uganda.
AB  - BACKGROUND: Healthcare utilization has particular relevance as a public health
      and development issue. Unlike material and human capital, there is little
      empirical evidence on the utility of social resources in overcoming barriers to
      healthcare utilization in a developing country context. We sought to assess the
      relevance of social resources in overcoming barriers to healthcare utilization.
      STUDY OBJECTIVE: To explore community perceptions among three different wealth
      categories on factors influencing healthcare utilization in Eastern Uganda.
      METHODS: We used a qualitative study design using Focus Group Discussions (FGD)
      to conduct the study. Community meetings were initially held to identify FGD
      participants in the different wealth categories, ('least poor', 'medium' and
      'poorest') using poverty ranking based on ownership of assets and income sources.
      Nine FGDs from three homogenous wealth categories were conducted. Data from the
      FGDs was analyzed using content analysis revealing common barriers as well as
      facilitating factors for healthcare service utilization by wealth categories. The
      Health Access Livelihood Framework was used to examine and interpret the
      findings. RESULTS: Barriers to healthcare utilization exist for all the wealth
      categories along three different axes including: the health seeking process;
      health services delivery; and the ownership of livelihood assets. Income source,
      transport ownership, and health literacy were reported as centrally useful in
      overcoming some barriers to healthcare utilization for the 'least poor' and
      'poor' wealth categories. The 'poorest' wealth category was keen to utilize free
      public health services. Conversely, there are perceptions that public health
      facilities were perceived to offer low quality care with chronic gaps such as
      shortages of essential supplies. In addition to individual material resources and
      the availability of free public healthcare services, social resources are
      perceived as important in overcoming utilization barriers. However, there are
      indications that having access to social resources may compensate for the lack of
      material resources in relation to use of health care services mainly for the
      least poor wealth category. CONCLUSION: The differential patterning of social
      resources may explain or contribute to the persisting inequities in health care
      utilization. Additional research using quantitative analytical methods is needed
      to test the robustness of the contribution of social resources to the utilization
      of and access to healthcare services.

PMID- 19602246
TI  - Closing the osteoporosis care gap: increased osteoporosis awareness among
      geriatrics and rehabilitation teams.
AB  - BACKGROUND: A care gap exists between recommendations and practice regarding the
      diagnosis and treatment of osteoporosis in fracture patients. The current study
      was designed to determine rates and predictors of in-hospital diagnosis and
      treatment of osteoporosis in patients admitted with fragility hip fractures, and
      to assess differences in these rates since the outset of the multipronged
      "Fracture? Think Osteoporosis" (FTOP) Program, which includes education of
      geriatrics and rehabilitation teams. METHODS: This is a retrospective cohort
      study conducted with data from two Hamilton, Ontario, university-based tertiary
      care hospitals, and represents a follow-up to a previous study conducted 8 years
      earlier. Data pertaining to all 354 patients, age > or = 50, admitted between
      March 2003 and April 2004, inclusive, with a diagnosis of fragility hip fracture
      were evaluated. Twelve patients were excluded leaving 342 patients for analysis,
      with 75% female, mean age 81.Outcomes included: Primary -- In-hospital diagnosis
      of osteoporosis and/or initiation of anti-resorptive treatment ("new osteoporosis
      diagnosis/treatment"). Secondary -- In-hospital mortality, BMD referrals, pre
      admission osteoporosis diagnosis and treatment. RESULTS: At admission, 27.8% of
      patients had a pre-existing diagnosis of osteoporosis and/or were taking anti
      resorptive treatment. Among patients with no previous osteoporosis
      diagnosis/treatment: 35.7% received a new diagnosis of osteoporosis, 21% were
      initiated on anti-resorptive treatment, and 14.3% received a BMD referral. The
      greatest predictor of new osteoporosis diagnosis/treatment was transfer to a
      rehabilitation or geriatrics unit: 79.5% of rehabilitation/geriatrics versus
      18.5% of patients receiving only orthopedics care met this outcome (p < 0.001).
      CONCLUSION: New diagnosis of osteoporosis among patients admitted with hip
      fracture has improved from 1.8% in the mid 1990's to 35.7%. Initiation of
      bisphosphonate therapy has likewise improved from 0% to 21%. Although multiple
      factors have likely contributed, the differential response between
      rehabilitation/geriatrics versus orthopedics patients suggests that education of
      the geriatric and rehabilitation teams, including one-on-one and group-based
      sessions, implemented as part of the FTOP Program, has played a role in this
      improvement. A significant care gap still exists for patients discharged directly
      from orthopedic units. The application of targeted inpatient and post-discharge
      initiatives, such as those that comprise the entire FTOP Program, may be of
      particular value in this setting.

PMID- 19602247
TI  - Yersinia outer protein YopE affects the actin cytoskeleton in Dictyostelium
      discoideum through targeting of multiple Rho family GTPases.
AB  - BACKGROUND: All human pathogenic Yersinia species share a virulence-associated
      type III secretion system that translocates Yersinia effector proteins into host
      cells to counteract infection-induced signaling responses and prevent
      phagocytosis. Dictyostelium discoideum has been recently used to study the
      effects of bacterial virulence factors produced by internalized pathogens. In
      this study we explored the potential of Dictyostelium as model organism for
      analyzing the effects of ectopically expressed Yersinia outer proteins (Yops).
      RESULTS: The Yersinia pseudotuberculosis virulence factors YopE, YopH, YopM and
      YopJ were expressed de novo within Dictyostelium and their effects on growth in
      axenic medium and on bacterial lawns were analyzed. No severe effect was observed
      for YopH, YopJ and YopM, but expression of YopE, which is a GTPase activating
      protein for Rho GTPases, was found to be highly detrimental. GFP-tagged YopE
      expressing cells had less conspicuous cortical actin accumulation and decreased
      amounts of F-actin. The actin polymerization response upon cAMP stimulation was
      impaired, although chemotaxis was unaffected. YopE also caused reduced uptake of
      yeast particles. These alterations are probably due to impaired Rac1 activation.
      We also found that YopE predominantly associates with intracellular membranes
      including the Golgi apparatus and inhibits the function of moderately
      overexpressed RacH. CONCLUSION: The phenotype elicited by YopE in Dictyostelium
      can be explained, at least in part, by inactivation of one or more Rho family
      GTPases. It further demonstrates that the social amoeba Dictyostelium discoideum
      can be used as an efficient and easy-to-handle model organism in order to analyze
      the function of a translocated GAP protein of a human pathogen.

PMID- 19602249
TI  - Comparison of reduction of edema after rest and after muscle exercises in
      treatment of chronic venous insufficiency.
AB  - AIM: The aim of this work was to compare the reduction in edema obtained in the
      conservative treatment of phlebopathies after resting and after performing a
      muscle exercise program in the Trendelenburg position. METHODS: Twenty-eight
      limbs of 24 patients with venous edema of distinct etiologies and classified as
      between C3 and C5 using CEAP classification. Volumetric evaluation by water
      displacement was carried out before and after resting in the Trendelenburg
      position and after performing programmed muscle exercises 24 hours later under
      identical conditions of time, position and temperature. For the statistical
      analysis the paired t-test was used with an alpha error of 5% being considered
      acceptable. RESULTS: The average total volume of the lower limbs was 3,967.46 mL.
      The mean reduction in edema obtained after resting was 92.9 mL, and after
      exercises it was 135.4 mL, giving a statistically significant difference (p-value
      = 0.0007). CONCLUSION: In conclusion, exercises are more efficient to reduce the
      edema of lower limbs than resting in the Trendelenburg position.

PMID- 19602248
TI  - Chloroquine and sulphadoxine-pyrimethamine sensitivity of Plasmodium falciparum
      parasites in a Brazilian endemic area.
AB  - BACKGROUND: The goal of the present study was the characterization of Plasmodium
      falciparum genes associated to malaria drug resistance (pfcrt, pfdhfr and
      pfdhps), in samples from two Brazilian localities. METHODS: Parasites from 65 P.
      falciparum samples were genotyped using nested-PCR and direct DNA sequencing.
      RESULTS: Six resistant sulphadoxine-pyrimethamine (SP) pfdhfr genotypes and one
      haplotype associated to SP sensitivity were detected. For pfcrt gene, SVMNT
      chloroquine (CQ)-resistant genotype was detected as well as the CVMNK CQ
      sensitive haplotype in the same sample from Paragominas, that showed a SP
      sensitive genotype. CONCLUSION: This study is the first to document the
      sensitivity of P. falciparum parasites to CQ and SP in Brazilian field samples.
      The importance of these findings is discussed.

PMID- 19602251
TI  - Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi
      method insights.
AB  - BACKGROUND: Ensuring good adherence is critical to the success of anti-retroviral
      treatment (ART). However, in resource-poor contexts, where paediatric HIV burden
      is high there has been limited progress in developing or adapting tools to
      support adherence for HIV-infected children on ART and their caregivers. We
      conducted formative research to assess children's adherence and to explore the
      knowledge, perceptions and attitudes of caregivers towards children's treatment.
      METHODS: All children starting ART between September 2002 and January 2004 (when
      ART was at cost in Malawi) were observed for at least 6 months on ART. Their
      adherence was assessed quantitatively by asking caregivers of children about
      missed ART doses during the previous 3 days at monthly visits. Attendance to
      clinic appointments was also monitored. In June and July 2004, four focus group
      discussions, each with 6 to 8 caregivers, and 5 critical incident narratives were
      conducted to provide complementary contextual data on caregivers' experiences on
      the challenges to and opportunities of paediatric ART adherence. RESULTS: We
      followed prospectively 47 children who started ART between 8 months and 12 years
      of age over a median time on ART of 33 weeks (2-91 weeks). 72% (34/47) never
      missed a single dose according to caregivers' report and 82% (327/401) of clinic
      visits were either as scheduled, or before or within 1 week after the scheduled
      appointment. Caregivers were generally knowledgeable about ART and motivated to
      support children to adhere to treatment despite facing multiple challenges.
      Caregivers were particularly motivated by seeing children begin to get better;
      but faced challenges in meeting the costs of medicine and transport, waiting
      times in clinic, stock outs and remembering to support children to adhere in the
      face of multiple responsibilities. CONCLUSION: In the era of rapid scale-up of
      treatment for children there is need for holistic support strategies that focus
      on the child, the caregiver and the health worker and which are situated within
      the reality of fragile health systems. The findings highlight the need for cost
      free and less complex paediatric ART regimes and culturally appropriate tools to
      support children's adherence.

PMID- 19602250
TI  - Acupuncture for persistent allergic rhinitis: a multi-centre, randomised,
      controlled trial protocol.
AB  - BACKGROUND: Allergic rhinitis is one of the most common health complaints
      worldwide. Complementary and alternative medical approaches have been employed to
      relieve allergic rhinitis symptoms and to avoid the side effects of conventional
      medication. Acupuncture has been widely used to treat patients with allergic
      rhinitis, but the available evidence of its effectiveness is insufficient. Our
      objective is to evaluate the effectiveness of acupuncture in patients in Korea
      and China with persistent allergic rhinitis compared to sham acupuncture
      treatment or waitlist control. METHODS: This study consists of a multi-centre
      (two centres in Korea and two centres in China), randomised, controlled trial
      with three parallel arms (active acupuncture, sham acupuncture, and waitlist
      group). The active acupuncture and sham acupuncture groups will receive real or
      sham acupuncture treatment, respectively, three times per week for a total of 12
      sessions over four weeks. Post-treatment follow-up will be performed a month
      later to complement these 12 acupuncture sessions. Participants in the waitlist
      group will not receive real or sham acupuncture treatments during this period but
      will only be required to keep recording their symptoms in a daily diary. After
      four weeks, the same treatment given to the active acupuncture group will be
      provided to the waitlist group. DISCUSSION: This trial will provide evidence for
      the effectiveness of acupuncture as a treatment for persistent allergic rhinitis.
      The primary outcome between groups is a change in the self-reported total nasal
      symptom score (i.e., nasal obstruction, rhinorrhea, sneezing, and itching) from
      baseline at the fourth week. Secondary outcome measures include the Rhinitis
      Quality of Life Questionnaire score and total non-nasal symptom score (i.e.,
      headache, itching, pain, eye-dropping). The quantity of conventional relief
      medication used during the follow-up period is another secondary outcome measure.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN90807007.

PMID- 19602252
TI  - Pulmonary involvement in Kaposi sarcoma: correlation between imaging and
      pathology.
AB  - Kaposi sarcoma is a low-grade mesenchymal tumor involving blood and lymphatic
      vessels. There are four variants of this disease, each presenting a different
      clinical manifestation: classic or sporadic, African or endemic, organ transplant
      related or iatrogenic, and AIDS-related or epidemic. Kaposi sarcoma is the most
      common tumor among patients with HIV infection, occurring predominantly in
      homosexual or bisexual men. The pulmonary involvement in Kaposi sarcoma occurs
      commonly in critically immunosupressed patients who commonly have had preceding
      mucocutaneous or digestive involvement.The etiology of Kaposi sarcoma is not
      precisely established; genetic, hormonal, and immune factors, as well as
      infectious agents, have all been implicated. There is evidence from
      epidemiologic, serologic, and molecular studies that Kaposi sarcoma is associated
      with human herpes virus type 8 infection. The disease starts as a reactive
      polyclonal angioproliferative response towards this virus, in which polyclonal
      cells change to form oligoclonal cell populations that expand and undergo
      malignant transformation.The diagnosis of pulmonary involvement in Kaposi sarcoma
      usually can be made by a combination of clinical, radiographic, and laboratory
      findings, together with the results of bronchoscopy and transbronchial biopsy.
      Chest high-resolution computed tomography scans commonly reveal
      peribronchovascular and interlobular septal thickening, bilateral and symmetric
      ill-defined nodules in a peribronchovascular distribution, fissural nodularity,
      mediastinal adenopathies, and pleural effusions. Correlation between the high
      resolution computed tomography findings and the pathology revealed by
      histopathological analysis demonstrate that the areas of central
      peribronchovascular infiltration represent tumor growth involving the
      bronchovascular bundles, with nodules corresponding to proliferations of
      neoplastic cells into the pulmonary parenchyma. The interlobular septal
      thickening may represent edema or tumor infiltration, and areas of ground-glass
      attenuation correspond to edema and the filling of air spaces with blood. These
      findings are a result of the propensity of Kaposi sarcoma to grow in the
      peribronchial and perivascular axial interstitial spaces, often as continuous
      sheets of tumor tissue.In conclusion, radiological findings can play a major role
      in the diagnosis of pulmonary Kaposi sarcoma since characteristic patterns may be
      observed. The presence of these patterns in patients with AIDS is highly
      suggestive of Kaposi sarcoma.

PMID- 19602255
TI  - Delay in the diagnosis of tuberculosis in Nepal.
AB  - BACKGROUND: Identifying reasons for delay in diagnosis and treatment of
      tuberculosis is important for the health system to find ways to treat patients as
      early as possible, and hence reduce the suffering of patients and transmission of
      the disease. The objectives of this study was to assess the duration of delay in
      the diagnosis of tuberculosis and to investigate its determinants. METHODS: A
      cross-sectional survey was conducted using a structured questionnaire in 307 new
      tuberculosis patients registered by the National Tuberculosis Programme (NTP) in
      all DOTS centres in Banke district of Nepal. RESULTS: The median patient delay
      was 50 days, the median health system delay was 18 days, and the median total
      delay was 60 days. Sputum smear negative participants had significantly lower
      risk of patient delay. Smokers using >5 cigarettes per day had higher risk of
      patient delay and health system delay. CONCLUSION: Total delay in the diagnosis
      of tuberculosis in Banke district is shorter compared to other places in Nepal
      and neighbouring countries. The shorter delay for smear negative pulmonary
      tuberculosis raises suspicion that many of these patients are not examined
      according to the NTP manual before being diagnosed. Increasing public awareness
      of the disease and expansion of the facilities with assured quality could be
      helpful to reduce the delay in the diagnosis of tuberculosis.

PMID- 19602253
TI  - A new tent trap for sampling exophagic and endophagic members of the Anopheles
      gambiae complex.
AB  - BACKGROUND: Mosquito sampling methods are essential for monitoring and evaluating
      malaria vector control interventions. In urban Dar es Salaam, human landing catch
      (HLC) is the only method sufficiently sensitive for monitoring malaria
      transmitting Anopheles. HLC is labour intensive, cumbersome, hazardous, and
      requires such intense supervision that is difficulty to sustain on large scales.
      METHODS: Novel tent traps were developed as alternatives to HLC. The Furvela
      tent, designed in Mozambique, incorporates a CDC Light trap (LT) components,
      while two others from Ifakara, Tanzania (designs A and B) require no electricity
      or moving parts. Their sensitivity for sampling malaria vectors was compared with
      LT and HLC over a wide range of vector abundances in rural and urban settings in
      Tanzania, with endophagic and exophagic populations, respectively, using
      randomised Latin-square and cross- over experimental designs. RESULTS: The
      sensitivity of LTs was greater than HLC while the opposite was true of Ifakara
      tent traps (crude mean catch of An. gambiae sensu lato relative to HLC = 0.28,
      0.65 and 1.30 for designs A, B and LT in a rural setting and 0.32 for design B in
      an urban setting). However, Ifakara B catches correlated far better to HLC (r2 =
      0.73, P < 0.001) than any other method tested (r2 = 0.04, P = 0.426 and r2 =
      0.19, P = 0.006 for Ifakara A and LTs respectively). Only Ifakara B in a rural
      setting with high vector density exhibited constant sampling efficiency relative
      to HLC. The relative sensitivity of Ifakara B increased as vector densities
      decreased in the urban setting and exceeded that of HLC at the lowest densities.
      None of the tent traps differed from HLC in terms of the proportions of parous
      mosquitoes (P >or= 0.849) or An. gambiae s.l. sibling species (P >or= 0.280) they
      sampled but both Ifakara A and B designs failed to reduce the proportion of blood
      fed mosquitoes caught (Odds ratio [95% Confidence Interval] = 1.6 [1.2, 2.1] and
      1.0 [0.8, 1.2], P = 0.002 and 0.998, respectively), probably because of operator
      exposure while emptying the trap each morning. CONCLUSION: The Ifakara B trap may
      have potential for monitoring and evaluating a variety of endophagic and
      exophagic Afrotropical malaria vectors, particularly at low but epidemiologically
      relevant population densities. However, operator exposure to mosquito bites
      remains a concern so additional modifications or protective measures will be
      required before this design can be considered for widespread, routine use.

PMID- 19602254
TI  - Differences in regulation of tight junctions and cell morphology between VHL
      mutations from disease subtypes.
AB  - BACKGROUND: In von Hippel-Lindau (VHL) disease, germline mutations in the VHL
      tumor suppressor gene cause clear cell renal carcinomas, hemangioblastomas, and
      pheochromocytomas. The VHL gene product is part of an ubiquitin E3 ligase complex
      and hypoxia-inducible factor alpha (HIF-alpha) is a key substrate, although
      additional VHL functions have been described. A genotype-phenotype relationship
      exists in VHL disease such that specific VHL mutations elicit certain subsets of
      these tumors. Here, we examine VHL genotype-phenotype correlations at the
      cellular level, focusing on the regulation of tight junctions and cell
      morphology. METHODS: Wild-type and various mutant VHL proteins representing VHL
      disease subtypes were stably expressed in 3 VHL-negative renal carcinoma cell
      lines. Using these cell lines, the roles of various VHL-associated cellular
      functions in regulation of cell morphology were investigated. RESULTS: As a
      whole, type 1 mutants varied greatly from type 2 mutants, demonstrating high
      levels of HIF-2alpha, cyclin D1 and alpha5 integrin, lower p27 levels, and a
      spindly, fibroblastic cellular appearance. Type 2 mutations demonstrated an
      epithelial morphology similar to wild-type VHL in the majority of the renal cell
      lines used. Knockdown of p27 in cells with wild-type VHL led to perturbations of
      both epithelial morphology and ZO-1 localization to tight junctions. ZO-1
      localization correlated well with VHL disease subtypes, with greater
      mislocalization observed for genotypes associated with a higher risk of renal
      carcinoma. HIF-2alpha knockdown in 786-O partially restored ZO-1 localization,
      but did not restore an epithelial morphology. CONCLUSION: VHL has both HIF-alpha
      dependent and HIF-alpha independent functions in regulating tight junctions and
      cell morphology that likely impact the clinical phenotypes seen in VHL disease.

PMID- 19602257
TI  - Src kinase up-regulates the ERK cascade through inactivation of protein
      phosphatase 2A following cerebral ischemia.
AB  - BACKGROUND: The regulation of protein phosphorylation requires a balance in the
      activity of protein kinases and protein phosphatases. Our previous data indicates
      that Src can increase ERK activity through Raf kinase in response to ischemic
      stimuli. This study examined the molecular mechanisms by which Src activates ERK
      cascade through protein phosphatases following cerebral ischemia. RESULTS:
      Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307
      leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up
      regulates PP2A activity, resulting in a significant decreased activity in ERK and
      its targets, CREB and ERalpha. In addition, the PP2A inhibitor, cantharidin, led
      to an up-regulation of ERK activity and was able to counteract Src inhibition
      during ischemia. CONCLUSION: Src induces up-regulation of ERK activity and its
      target transcription factors, CREB and ERalpha, through attenuation of PP2A
      activity. Therefore, activation of ERK is the result of a crosstalk between two
      pathways, Raf-dependent positive regulators and PP2A-dependent negative
      regulators.

PMID- 19602256
TI  - The joint influence of area income, income inequality, and immigrant density on
      adverse birth outcomes: a population-based study.
AB  - BACKGROUND: The association between area characteristics and birth outcomes is
      modified by race. Whether such associations vary according to social class
      indicators beyond race has not been assessed. METHODS: This study evaluated
      effect modification by maternal birthplace and education of the relationship
      between neighbourhood characteristics and birth outcomes of newborns from 1999
      2003 in the province of Quebec, Canada (N = 353,120 births). Areas (N = 143) were
      defined as administrative local health service delivery districts. Multi-level
      logistic regression was used to model the association between three area
      characteristics (median household income, immigrant density and income
      inequality) and the two outcomes preterm birth (PTB) and small-for-gestational
      age (SGA) birth. Effect modification by social class indicators was evaluated in
      analyses stratified according to maternal birthplace and education. RESULTS:
      Relative to the lowest tertile, high median household income was associated with
      SGA birth among Canadian-born mothers (odds ratio (OR) 1.13, 95% confidence
      interval (CI) 1.06, 1.20) and mothers with high school education or less (OR
      1.13, 95% CI 1.02, 1.24). Associations between median household income and PTB
      were weaker. Relative to the highest tertile, low immigrant density was
      associated with a lower odds of PTB among foreign-born mothers (OR 0.79, 95% CI
      0.63, 1.00) but a higher odds of PTB among Canadian-born mothers (OR 1.14, 95% CI
      1.07, 1.21). Associations with income inequality were weak or absent. CONCLUSION:
      The association between area factors and birth outcomes is modified by maternal
      birthplace and education. Studies have found that race interacts in a similar
      manner. Public health policies focussed on perinatal health must consider the
      interaction between individual and area characteristics.

PMID- 19602258
TI  - Significance of common variants on human chromosome 8q24 in relation to the risk
      of prostate cancer in native Japanese men.
AB  - BACKGROUND: Common variants on human chromosome 8q24, rs1447295 (C/A) and
      rs6983267 (T/G), have been recently linked to the prevalence of prostate cancer
      in European and American populations. Here, we evaluated whether the single
      nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of
      sporadic prostate cancer as well as latent prostate cancer in a native Japanese
      population. RESULTS: We analyzed genomic DNA samples from 391 sporadic prostate
      cancer patients, 323 controls who had died from causes unrelated to cancer and
      112 Japanese men who were diagnosed as having latent prostate cancer based on
      autopsy results. The polymorphisms were determined by allelic discrimination
      using a fluorescent-based TaqMan assay. The A allele of rs1447295 was
      significantly associated with the risk of sporadic prostate cancer (p = 0.04; age
      adjusted OR, 1.34), while the G allele of rs6983267 showed a trend towards being
      a high-risk allele (p = 0.06; age-adjusted OR, 1.27). No significant difference
      between these two polymorphisms and the risk of latent prostate cancer was
      observed in the present Japanese population. CONCLUSION: Known variants on human
      chromosome 8q24 may be risk factors for sporadic prostate cancer in native
      Japanese men.

PMID- 19602259
TI  - Activation of the pre-supplementary motor area but not inferior prefrontal cortex
      in association with short stop signal reaction time--an intra-subject analysis.
AB  - BACKGROUND: Our previous work described the neural processes of motor response
      inhibition during a stop signal task (SST). Employing the race model, we computed
      the stop signal reaction time (SSRT) to index individuals' ability in inhibitory
      control. The pre-supplementary motor area (preSMA), which shows greater activity
      in individuals with short as compared to those with long SSRT, plays a role in
      mediating response inhibition. In contrast, the right inferior prefrontal cortex
      (rIFC) showed greater activity during stop success as compared to stop error.
      Here we further pursued this functional differentiation of preSMA and rIFC on the
      basis of an intra-subject approach. RESULTS: Of 65 subjects who participated in
      four sessions of the SST, we identified 30 individuals who showed a difference in
      SSRT but were identical in other aspects of stop signal performance between the
      first ("early") and last two ("late") sessions. By comparing regional brain
      activation between the two sessions, we confirmed greater preSMA but not rIFC
      activity during short as compared to long SSRT session within individuals.
      Furthermore, putamen, anterior cerebellum and middle/posterior cingulate cortex
      also showed greater activity in association with short SSRT. CONCLUSION: These
      results are consistent with a role of medial prefrontal cortex in controlled
      action and inferior frontal cortex in orienting attention. We discussed these
      findings with respect to the process of attentional monitoring and inhibitory
      motor control during stop signal inhibition.

PMID- 19602261
TI  - Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters.
AB  - BACKGROUND: Modellers using the MWC allosteric framework have often found it
      difficult to validate their models. Indeed many experiments are not conducted
      with the notion of alternative conformations in mind and therefore do not (or
      cannot) measure relevant microscopic constant and parameters. Instead,
      experimentalists widely use the Adair-Klotz approach in order to describe their
      experimental data. RESULTS: We propose a way of computing apparent Adair-Klotz
      constants from microscopic association constants and allosteric parameters of a
      generalised concerted model with two different states (R and T), with an
      arbitrary number of non-equivalent ligand binding sites. We apply this framework
      to compute Adair-Klotz constants from existing models of calmodulin and
      hemoglobin, two extreme cases of the general framework. CONCLUSION: The
      validation of computational models requires methods to relate model parameters to
      experimentally observable quantities. We provide such a method for comparing
      generalised MWC allosteric models to experimentally determined Adair-Klotz
      constants.

PMID- 19602260
TI  - Evolution of plant senescence.
AB  - BACKGROUND: Senescence is integral to the flowering plant life-cycle. Senescence
      like processes occur also in non-angiosperm land plants, algae and photosynthetic
      prokaryotes. Increasing numbers of genes have been assigned functions in the
      regulation and execution of angiosperm senescence. At the same time there has
      been a large expansion in the number and taxonomic spread of plant sequences in
      the genome databases. The present paper uses these resources to make a study of
      the evolutionary origins of angiosperm senescence based on a survey of the
      distribution, across plant and microbial taxa, and expression of senescence
      related genes. RESULTS: Phylogeny analyses were carried out on protein sequences
      corresponding to genes with demonstrated functions in angiosperm senescence. They
      include proteins involved in chlorophyll catabolism and its control, homeoprotein
      transcription factors, metabolite transporters, enzymes and regulators of
      carotenoid metabolism and of anthocyanin biosynthesis. Evolutionary timelines for
      the origins and functions of particular genes were inferred from the taxonomic
      distribution of sequences homologous to those of angiosperm senescence-related
      proteins. Turnover of the light energy transduction apparatus is the most ancient
      element in the senescence syndrome. By contrast, the association of
      phenylpropanoid metabolism with senescence, and integration of senescence with
      development and adaptation mediated by transcription factors, are relatively
      recent innovations of land plants. An extended range of senescence-related genes
      of Arabidopsis was profiled for coexpression patterns and developmental
      relationships and revealed a clear carotenoid metabolism grouping, coordinated
      expression of genes for anthocyanin and flavonoid enzymes and regulators and a
      cluster pattern of genes for chlorophyll catabolism consistent with functional
      and evolutionary features of the pathway. CONCLUSION: The expression and
      phylogenetic characteristics of senescence-related genes allow a framework to be
      constructed of decisive events in the evolution of the senescence syndrome of
      modern land-plants. Combining phylogenetic, comparative sequence, gene expression
      and morphogenetic information leads to the conclusion that biochemical, cellular,
      integrative and adaptive systems were progressively added to the ancient primary
      core process of senescence as the evolving plant encountered new environmental
      and developmental contexts.

PMID- 19602263
TI  - Fitting multilevel models in complex survey data with design weights:
      Recommendations.
AB  - BACKGROUND: Multilevel models (MLM) offer complex survey data analysts a unique
      approach to understanding individual and contextual determinants of public
      health. However, little summarized guidance exists with regard to fitting MLM in
      complex survey data with design weights. Simulation work suggests that analysts
      should scale design weights using two methods and fit the MLM using unweighted
      and scaled-weighted data. This article examines the performance of scaled
      weighted and unweighted analyses across a variety of MLM and software programs.
      METHODS: Using data from the 2005-2006 National Survey of Children with Special
      Health Care Needs (NS-CSHCN: n = 40,723) that collected data from children
      clustered within states, I examine the performance of scaling methods across
      outcome type (categorical vs. continuous), model type (level-1, level-2, or
      combined), and software (Mplus, MLwiN, and GLLAMM). RESULTS: Scaled weighted
      estimates and standard errors differed slightly from unweighted analyses,
      agreeing more with each other than with unweighted analyses. However, observed
      differences were minimal and did not lead to different inferential conclusions.
      Likewise, results demonstrated minimal differences across software programs,
      increasing confidence in results and inferential conclusions independent of
      software choice. CONCLUSION: If including design weights in MLM, analysts should
      scale the weights and use software that properly includes the scaled weights in
      the estimation.

PMID- 19602264
TI  - Measurement of pharyngeal sensory cortical processing: technique and physiologic
      implications.
AB  - BACKGROUND: Dysphagia is a major complication of different diseases affecting
      both the central and peripheral nervous system. Pharyngeal sensory impairment is
      one of the main features of neurogenic dysphagia. Therefore an objective
      technique to examine the cortical processing of pharyngeal sensory input would be
      a helpful diagnostic tool in this context. We developed a simple paradigm to
      perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head
      MEG was employed to study changes in cortical activation during this pharyngeal
      stimulation in nine healthy subjects. Data were analyzed by means of synthetic
      aperture magnetometry (SAM) and the group analysis of individual SAM data was
      performed using a permutation test. RESULTS: Our results revealed bilateral
      activation of the caudolateral primary somatosensory cortex following sensory
      pharyngeal stimulation with a slight lateralization to the side of stimulation.
      CONCLUSION: The method introduced here is simple and easy to perform and might be
      applicable in the clinical setting. The results are in keeping with previous
      findings showing bihemispheric involvement in the complex task of sensory
      pharyngeal processing. They might also explain changes in deglutition after
      hemispheric strokes. The ipsilaterally lateralized processing is surprising and
      needs further investigation.

PMID- 19602262
TI  - Potential markers of preeclampsia--a review.
AB  - Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and
      morbidity worldwide. The early identification of patients with an increased risk
      for preeclampsia is therefore one of the most important goals in obstetrics. The
      availability of highly sensitive and specific physiologic and biochemical markers
      would allow not only the detection of patients at risk but also permit a close
      surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as
      well as simplified recruitment for future studies looking at therapeutic
      medications and additional prospective markers. Today, several markers may offer
      the potential to be used, most likely in a combinatory analysis, as predictors or
      diagnostic tools. We present here the current knowledge on the biology of
      preeclampsia and review several biochemical markers which may be used to monitor
      preeclampsia in a future, that, we hope, is not to distant from today.

PMID- 19602265
TI  - Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pleiotropic
      cytokine and mediator of acute and chronic inflammatory diseases. MIF is
      overexpressed in various tumours and has been suggested as a molecular link
      between chronic inflammation and cancer. MIF overexpression is observed in breast
      cancer but its causal role in the development of this tumour entity is unclear.
      METHODS: MIF levels in breast cancer cell lines were determined by ELISA and
      Western blot. CD74 was measured by Western blot, fluorescence microscopy and flow
      cytometry. Cell proliferation was studied by BrdU incorporation, cell adhesion by
      Matrigel adhesion assay, and cell invasion by migration assay through Matrigel
      coated filters using the Transwell system. MIF expression in primary human breast
      cancers was measured by tissue microarray and a semi-quantitative
      immunoreactivity score (IRS) and comparison with histopathological parameters and
      patient outcome data. RESULTS: MIF was abundantly expressed in the non-invasive
      breast cancer cell lines MDA-MB-468 and ZR-75-1, but not in invasive MDA-MB-231
      cells, which in turn expressed higher levels of the MIF-receptor CD74.
      Stimulation with exogenous MIF led to a dramatic upregulation of MIF secretion
      (50-fold) in MDA-MB-231 cells. Autocrine MIF promoted tumour cell proliferation,
      as indicated by blockade of MIF or CD74 in MDA-MB-231 and MDA-MB-468, and MDA-MB
      231 invasiveness was enhanced by exogenous MIF. We correlated the expression of
      MIF with histopathological parameters and patient outcome data, using a tissue
      microarray of 175 primary invasive breast cancers and 35 normal control tissues.
      MIF was upregulated in breast cancer versus normal tissue (median IRS = 8 versus
      6). MIF expression showed positive correlations with progesterone (p = 0.006) and
      estrogen (p = 0.028) receptor expression, markers of a favourable prognosis and a
      negative correlation to tumour size (p = 0.007). In line with these data, disease
      specific overall (OS) as well as recurrence-free (RFS) survival was significantly
      improved in breast cancer patients with abundant cytosolic MIF expression
      compared to MIF low expressers (5-year OS = 67% versus 50%, p = 0.0019; 5-year
      RFS = 52% versus 36%, p = 0.0327). CONCLUSION: We conclude that intracellular
      expression of MIF in breast cancer cells is beneficial, whereas extracellular MIF
      may play a pro-oncogenic role in promoting breast cancer cell-stroma
      interactions.

PMID- 19602266
TI  - IS711-based real-time PCR assay as a tool for detection of Brucella spp. in wild
      boars and comparison with bacterial isolation and serology.
AB  - BACKGROUND: Control of brucellosis in livestock, wildlife and humans depends on
      the reliability of the methods used for detection and identification of bacteria.
      In the present study, we describe the evaluation of the recently established real
      time PCR assay based on the Brucella-specific insertion sequence IS711 with blood
      samples from 199 wild boars (first group of animals) and tissue samples from 53
      wild boars (second group of animals) collected in Switzerland. Results from IS711
      real-time PCR were compared to those obtained by bacterial isolation, Rose Bengal
      Test (RBT), competitive ELISA (c-ELISA) and indirect ELISA (i-ELISA). RESULTS: In
      the first group of animals, IS711 real-time PCR detected infection in 11.1%
      (16/144) of wild boars that were serologically negative. Serological tests showed
      different sensitivities [RBT 15.6%, c-ELISA 7.5% and i-ELISA 5.5%] and only 2% of
      blood samples were positive with all three tests, which makes interpretation of
      the serological results very difficult. Regarding the second group of animals,
      the IS711 real-time PCR detected infection in 26% of animals, while Brucella spp.
      could be isolated from tissues of only 9.4% of the animals. CONCLUSION: The
      results presented here indicate that IS711 real-time PCR assay is a specific and
      sensitive tool for detection of Brucella spp. infections in wild boars. For this
      reason, we propose the employment of IS711 real-time PCR as a complementary tool
      in brucellosis screening programs and for confirmation of diagnosis in doubtful
      cases.

PMID- 19602267
TI  - Temporal and geographic evidence for evolution of Sin Nombre virus using
      molecular analyses of viral RNA from Colorado, New Mexico and Montana.
AB  - BACKGROUND: All viruses in the family Bunyaviridae possess a tripartite genome,
      consisting of a small, a medium, and a large RNA segment. Bunyaviruses therefore
      possess considerable evolutionary potential, attributable to both intramolecular
      changes and to genome segment reassortment. Hantaviruses (family Bunyaviridae,
      genus Hantavirus) are known to cause human hemorrhagic fever with renal syndrome
      or hantavirus pulmonary syndrome. The primary reservoir host of Sin Nombre virus
      is the deer mouse (Peromyscus maniculatus), which is widely distributed in North
      America. We investigated the prevalence of intramolecular changes and of genomic
      reassortment among Sin Nombre viruses detected in deer mice in three western
      states. METHODS: Portions of the Sin Nombre virus small (S) and medium (M) RNA
      segments were amplified by RT-PCR from kidney, lung, liver and spleen of
      seropositive peromyscine rodents, principally deer mice, collected in Colorado,
      New Mexico and Montana from 1995 to 2007. Both a 142 nucleotide (nt) amplicon of
      the M segment, encoding a portion of the G2 transmembrane glycoprotein, and a 751
      nt amplicon of the S segment, encoding part of the nucleocapsid protein, were
      cloned and sequenced from 19 deer mice and from one brush mouse (P. boylii), S
      RNA but not M RNA from one deer mouse, and M RNA but not S RNA from another deer
      mouse. RESULTS: Two of 20 viruses were found to be reassortants. Within virus
      sequences from different rodents, the average rate of synonymous substitutions
      among all pair-wise comparisons (pis) was 0.378 in the M segment and 0.312 in the
      S segment sequences. The replacement substitution rate (pia) was 7.0 x 10-4 in
      the M segment and 17.3 x 10-4 in the S segment sequences. The low pia relative to
      pis suggests strong purifying selection and this was confirmed by a Fu and Li
      analysis. The absolute rate of molecular evolution of the M segment was 6.76 x 10
      3 substitutions/site/year. The absolute age of the M segment tree was estimated
      to be 37 years. In the S segment the rate of molecular evolution was 1.93 x 10-3
      substitutions/site/year and the absolute age of the tree was 106 years. Assuming
      that mice were infected with a single Sin Nombre virus genotype, phylogenetic
      analyses revealed that 10% (2/20) of viruses were reassortants, similar to the
      14% (6/43) found in a previous report. CONCLUSION: Age estimates from both
      segments suggest that Sin Nombre virus has evolved within the past 37-106 years.
      The rates of evolutionary changes reported here suggest that Sin Nombre virus M
      and S segment reassortment occurs frequently in nature.

PMID- 19602268
TI  - Measuring patient perceptions about osteoporosis pharmacotherapy.
AB  - BACKGROUND: Adherence to osteoporosis pharmacotherapy is poor, and linked with
      patient perceptions of the benefits of, and barriers to taking these treatments.
      To better understand the association between patient perceptions and osteoporosis
      pharmacotherapy, we generated thirteen items that may tap into patient
      perceptions about the benefits of, and barriers to osteoporosis treatment; and
      included these items as part of a standardized telephone interview of women aged
      65-90 years (n = 871). The purpose of this paper is to report the psychometric
      evaluation of our scale. FINDINGS: Upon detailed analysis, six of the thirteen
      items were omitted: four redundant, one did not correlate well with any other
      item and one factorial complex. From the remaining seven items, two distinct
      unidimensional domains emerged (variance explained = 78%). Internal consistency
      of the 5-item osteoporosis drug treatment benefits domain was good (Cronbach's
      alpha = 0.88), and was supported by construct validity; women reporting a
      physician-diagnosis or taking osteoporosis pharmacotherapy had higher
      osteoporosis treatment benefit scores compared to those reporting no osteoporosis
      diagnosis or treatment respectively. Because only two items were identified as
      tapping into treatment barriers, we recommend they each be used as a separate
      item assessing potential barriers to adherence to osteoporosis pharmacotherapy,
      rather than combined into a single scale. CONCLUSION: The 5-item osteoporosis
      drug treatment benefits scale may be useful to examine perceptions about the
      benefits of osteoporosis pharmacotherapy. Further research is needed to develop
      scales that adequately measure perceived barriers to osteoporosis
      pharmacotherapy.

PMID- 19602269
TI  - Intracellular Mycoplasma genitalium infection of human vaginal and cervical
      epithelial cells elicits distinct patterns of inflammatory cytokine secretion and
      provides a possible survival niche against macrophage-mediated killing.
AB  - BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen
      that has been associated with significant reproductive tract inflammatory
      syndromes in women. In addition, the strong association between severity of M.
      genitalium infection and Human Immunodeficiency Virus type 1 (HIV-1) shedding
      from the cervix suggests that innate responses to M. genitalium may influence
      pathogenesis of other sexually transmitted infections. Epithelial cells (ECs) of
      the reproductive mucosa are the first cells contacted by sexually transmitted
      pathogens. Therefore, we first characterized the dynamics of intracellular and
      extracellular localization and resultant innate immune responses from human
      vaginal, ecto- and endocervical ECs to M. genitalium type strain G37 and a low
      pass contemporary isolate, M2300. RESULTS: Both M. genitalium strains rapidly
      attached to vaginal and cervical ECs by 2 h post-infection (PI). By 3 h PI, M.
      genitalium organisms also were found in intracellular membrane-bound vacuoles of
      which approximately 60% were adjacent to the nucleus. Egress of M. genitalium
      from infected ECs into the culture supernatant was observed but, after invasion,
      viable intracellular titers were significantly higher than extracellular titers
      at 24 and 48 h PI. All of the tested cell types responded by secreting
      significant levels of pro-inflammatory cytokines and chemokines in a pattern
      consistent with recruitment and stimulation of monocytes and macrophages. Based
      on the elaborated cytokines, we next investigated the cellular interaction of M.
      genitalium with human monocyte-derived macrophages and characterized the
      resultant cytokine responses. Macrophages rapidly phagocytosed M. genitalium
      resulting in a loss of bacterial viability and a potent pro-inflammatory response
      that included significant secretion of IL-6 and other cytokines associated with
      enhanced HIV-1 replication. The macrophage-stimulating capacity of M. genitalium
      was independent of bacterial viability but was sensitive to heat denaturation and
      proteinase-K digestion suggesting that M. genitalium protein components are the
      predominant mediators of inflammation. CONCLUSION: Collectively, the data
      indicated that human genital ECs were susceptible and immunologically responsive
      to M. genitalium infection that likely induced cellular immune responses.
      Although macrophage phagocytosis was an effective method for M. genitalium
      killing, intracellular localization within vaginal and cervical ECs may provide
      M. genitalium a survival niche and protection from cellular immune responses
      thereby facilitating the establishment and maintenance of reproductive tract
      infection.

PMID- 19602270
TI  - Association between ACE gene I/D polymorphisms and hyperandrogenism in women with
      polycystic ovary syndrome (PCOS) and controls.
AB  - BACKGROUND: I/D polymorphisms of ACE are associated with the plasma ACE
      concentration. The ACE is associated with the angiogenesis of ovarian endothelium
      in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE
      induces a high blood supply and hypersteroidogenesis in the ovary, it may be
      associated with polycystic ovary syndrome (PCOS) which exhibits hyperplasia,
      hypervascularity of the ovarian theca interna and stroma, as well as disorderd
      steroidogenesis. Therefore, we hypothesized that the ACE plays some roles in the
      human ovary. To investigate whether the ACE I/D polymorphisms are associated with
      the steroidogenesis disorder in PCOS and contribute to the susceptibility of PCOS
      in Chinese women, we designed a case-controlled association study in 582
      individuals. METHODS: The ACE I/D polymorphisms were assessed in 582 reproductive
      age women. Genotyping and frequency of ACE I/D polymorphisms were obtained by PCR
      amplification that was performed on genomic DNA isolated from blood leucocytes.
      Results were analyzed in respect to clinical test results. RESULTS: The
      frequencies of the D allele and the genotypic distributions (DD, ID and II) in
      the women with PCOS did not differ from those in controls (P = 0.458). However,
      there were significant differences in the concentrations of testosterone among
      three genotypes both in the PCOS patients and controls (P = 0.0045, P = 0.0052,
      respectively). Differences were also found between these groups with distinct
      genotypes: DD versus II and DI versus II in the PCOS patients as well as DD
      versus DI and DD versus II in the controls. There were significant differences in
      the ratio of LH/FSH among three genotypes in the patients (P = 0.01). However,
      there were no statistical differences in the BMI, AAM, E2 concentrations and
      other serum hormone concentrations among the three genotypes both in the PCOS
      patients and controls. CONCLUSION: The ACE I/D polymorphisms were not associated
      with the pathogenesis of PCOS. However, the polymorphisms were associated with
      the steroidogenesis in the ovary. The observation indicated that the ACE I/D
      polymorphisms were not the key etiological factor, which in stead may be
      associated with the aggravated clinical manifestations of PCOS.

PMID- 19602271
TI  - Dendrites differ from axons in patterns of microtubule stability and
      polymerization during development.
AB  - BACKGROUND: Dendrites differ from axons in patterns of growth and development, as
      well as in morphology. Given that microtubules are key structural elements in
      cells, we assessed patterns of microtubule stability and polymerization during
      hippocampal neuron development in vitro to determine if these aspects of
      microtubule organization could distinguish axons from dendrites. RESULTS:
      Quantitative ratiometric immunocytochemistry identified significant differences
      in microtubule stability between axons and dendrites. Most notably, regardless of
      developmental stage, there were high levels of dynamic microtubules throughout
      the dendritic arbor, whereas dynamic microtubules were predominantly concentrated
      in the distal end of axons. Analysis of microtubule polymerization using green
      fluorescent protein-tagged EB1 showed both developmental and regional differences
      in microtubule polymerization between axons and dendrites. Early in development
      (for example, 1 to 2 days in vitro), polymerization events were distributed
      equally in both the anterograde and retrograde directions throughout the length
      of both axons and dendrites. As development progressed, however, polymerization
      became biased, with a greater number of polymerization events in distal than in
      proximal and middle regions. While polymerization occurred almost exclusively in
      the anterograde direction for axons, both anterograde and retrograde
      polymerization was observed in dendrites. This is in agreement with predicted
      differences in microtubule polarity within these compartments, although fewer
      retrograde events were observed in dendrites than expected. CONCLUSION: Both
      immunocytochemical and live imaging analyses showed that newly formed
      microtubules predominated at the distal end of axons and dendrites, suggesting a
      common mechanism that incorporates increased microtubule polymerization at
      growing process tips. Dendrites had more immature, dynamic microtubules
      throughout the entire arbor than did axons, however. Identifying these
      differences in microtubule stability and polymerization is a necessary first step
      toward understanding how they are developmentally regulated, and may reveal novel
      mechanisms underlying neuron maturation and dendritic plasticity that extend
      beyond the initial specification of polarity.

PMID- 19602272
TI  - Chick Lrrn2, a novel downstream effector of Hoxb1 and Shh, functions in the
      selective targeting of rhombomere 4 motor neurons.
AB  - BACKGROUND: Capricious is a Drosophila adhesion molecule that regulates specific
      targeting of a subset of motor neurons to their muscle target. We set out to
      identify whether one of its vertebrate homologues, Lrrn2, might play an analogous
      role in the chick. RESULTS: We have shown that Lrrn2 is expressed from early
      development in the prospective rhombomere 4 (r4) of the chick hindbrain.
      Subsequently, its expression in the hindbrain becomes restricted to a specific
      group of motor neurons, the branchiomotor neurons of r4, and their pre-muscle
      target, the second branchial arch (BA2), along with other sites outside the
      hindbrain. Misexpression of the signalling molecule Sonic hedgehog (Shh) via in
      ovo electroporation results in upregulation of Lrrn2 exclusively in r4, while the
      combined expression of Hoxb1 and Shh is sufficient to induce ectopic Lrrn2 in
      r1/2. Misexpression of Lrrn2 in r2/3 results in axonal rerouting from the r2 exit
      point to the r4 exit point and BA2, suggesting a direct role in motor axon
      guidance. CONCLUSION: Lrrn2 acts downstream of Hoxb1 and plays a role in the
      selective targeting of r4 motor neurons to BA2.

PMID- 19602273
TI  - Relationships among neurocognition, symptoms and functioning in patients with
      schizophrenia: a path-analytic approach for associations at baseline and
      following 24 weeks of antipsychotic drug therapy.
AB  - BACKGROUND: Neurocognitive impairment and psychiatric symptoms have been
      associated with deficits in psychosocial and occupational functioning in patients
      with schizophrenia. This post-hoc analysis evaluates the relationships among
      cognition, psychopathology, and psychosocial functioning in patients with
      schizophrenia at baseline and following sustained treatment with antipsychotic
      drugs. METHODS: Data were obtained from a clinical trial assessing the cognitive
      effects of selected antipsychotic drugs in patients with schizophrenia. Patients
      were randomly assigned to 24 weeks of treatment with olanzapine (n = 159),
      risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was
      assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with
      a standard battery of neurocognitive tests; and psychiatric symptoms with the
      Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used
      to evaluate the effects of changes in cognitive functioning on subdomains of
      quality of life, and to determine whether such effects were direct or mediated
      via changes in psychiatric symptoms. RESULTS: At baseline, processing speed
      affected functioning mainly indirectly via negative symptoms. Positive symptoms
      also affected functioning at baseline although independent of cognition. At 24
      weeks, changes in processing speed affected changes in functioning both directly
      and indirectly via PANSS negative subscale scores. Positive symptoms no longer
      contributed to the path-analytic models. Although a consistent relationship was
      observed between processing speed and the 3 functional domains, variation existed
      as to whether the paths were direct and/or indirect. Working memory and verbal
      memory did not significantly contribute to any of the path-analytic models
      studied. CONCLUSION: Processing speed demonstrated direct and indirect effects
      via negative symptoms on three domains of functioning as measured by the QLS at
      baseline and following 24 weeks of antipsychotic treatment.

PMID- 19602274
TI  - Mathematical modeling supports substantial mouse neural progenitor cell death.
AB  - BACKGROUND: Existing quantitative models of mouse cerebral cortical development
      are not fully constrained by experimental data. RESULTS: Here, we use simple
      difference equations to model neural progenitor cell fate decisions,
      incorporating intermediate progenitor cells and initially low rates of neural
      progenitor cell death. Also, we conduct a sensitivity analysis to investigate
      possible uncertainty in the fraction of cells that divide, differentiate, and die
      at each cell cycle. CONCLUSION: We demonstrate that uniformly low-level neural
      progenitor cell death, as concluded in previous models, is incompatible with
      normal mouse cortical development. Levels of neural progenitor cell death up to
      and exceeding 50% are compatible with normal cortical development and may operate
      to prevent forebrain overgrowth as observed following cell death attenuation, as
      occurs in caspase 3-null mutant mice.

PMID- 19602275
TI  - Three different Plasmodium species show similar patterns of clinical tolerance of
      malaria infection.
AB  - BACKGROUND: In areas where malaria endemicity is high, many people harbour blood
      stage parasites without acute febrile illness, complicating the estimation of
      disease burden from infection data. For Plasmodium falciparum the density of
      parasitaemia that can be tolerated is low in the youngest children, but reaches a
      maximum in the age groups at highest risk of infection. There is little data on
      the age dependence of tolerance in other species of human malaria. METHODS:
      Parasite densities measured in 24,386 presumptive malaria cases at two local
      health centres in the Wosera area of Papua New Guinea were compared with the
      distributions of parasite densities recorded in community surveys in the same
      area. We then analyse the proportions of cases attributable to each of Plasmodium
      falciparum, P. vivax, and P. malariae as functions of parasite density and age
      using a latent class model. These attributable fractions are then used to compute
      the incidence of attributable disease. RESULTS: Overall 33.3%, 6.1%, and 0.1% of
      the presumptive cases were attributable to P. falciparum, P. vivax, and P.
      malariae respectively. The incidence of attributable disease and parasite density
      broadly follow similar age patterns. The logarithm of the incidence of acute
      illness is approximately proportion to the logarithm of the parasite density for
      all three malaria species, with little age variation in the relationship for P.
      vivax or P. malariae. P. falciparum shows more age variation in disease incidence
      at given levels of parasitaemia than the other species. CONCLUSION: The
      similarities between Plasmodium species in the relationships between parasite
      density and risk of attributable disease are compatible with the hypothesis that
      pan-specific mechanisms may regulate tolerance to different human Plasmodia. A
      straightforward mathematical expression might be used to project disease burden
      from parasite density distributions assessed in community-based parasitological
      surveys.

PMID- 19602277
TI  - Metabolic Bone Disease in preterm newborn: an update on nutritional issues.
AB  - Osteopenia, a condition characterised by a reduction in bone mineral content, is
      a common disease of preterm babies between the tenth and sixteenth week of life.
      Prematurely born infants are deprived of the intrauterine supply of minerals
      affecting bone mineralization.The aetiology is multifactorial: inadequate
      nutrients intake (calcium, phosphorus and vitamin D), a prolonged period of total
      parenteral nutrition, immobilisation and the intake of some drugs.The diagnosis
      of metabolic bone disease is done by biochemical analysis: low serum levels of
      phosphorus and high levels of alkaline phosphatase are suggestive of metabolic
      bone disease. The disease can remain clinically silent or presents with symptoms
      and signs of rachitism depending on the severity of bone demineralisation.An
      early nutritional intervention can reduce both the prevalence and the severity of
      osteopenia.This article reviews the pathophysiology of foetal and neonatal bone
      metabolism, focuses on the nutrient requirements of premature babies and on the
      ways to early detect and treat osteopenia.

PMID- 19602276
TI  - Illuminating the life of GPCRs.
AB  - The investigation of biological systems highly depends on the possibilities that
      allow scientists to visualize and quantify biomolecules and their related
      activities in real-time and non-invasively. G-protein coupled receptors represent
      a family of very dynamic and highly regulated transmembrane proteins that are
      involved in various important physiological processes. Since their localization
      is not confined to the cell surface they have been a very attractive "moving
      target" and the understanding of their intracellular pathways as well as the
      identified protein-protein-interactions has had implications for therapeutic
      interventions. Recent and ongoing advances in both the establishment of a variety
      of labeling methods and the improvement of measuring and analyzing
      instrumentation, have made fluorescence techniques to an indispensable tool for
      GPCR imaging. The illumination of their complex life cycle, which includes
      receptor biosynthesis, membrane targeting, ligand binding, signaling,
      internalization, recycling and degradation, will provide new insights into the
      relationship between spatial receptor distribution and function. This review
      covers the existing technologies to track GPCRs in living cells. Fluorescent
      ligands, antibodies, auto-fluorescent proteins as well as the evolving
      technologies for chemical labeling with peptide- and protein-tags are described
      and their major applications concerning the GPCR life cycle are presented.

PMID- 19602278
TI  - Tetraspanins regulate cell-to-cell transmission of HIV-1.
AB  - BACKGROUND: The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1
      budding sites, at the virological synapse (VS), and their enrichment in HIV-1
      virions has been well-documented, but it remained unclear if these proteins play
      a role in the late phase of the viral replication cycle. Here we used
      overexpression and knockdown approaches to address this question. RESULTS:
      Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these
      tetraspanins was found to affect the efficiency of virus release. However,
      confirming recently reported data, tetraspanin overexpression in virus-producing
      cells resulted in the release of virions with substantially reduced infectivity.
      We also investigated the roles of these tetraspanins in cell-to-cell transmission
      of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission
      of this virus. Interestingly, in knockdown experiments we found that ablation of
      CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown
      of CD81, but not CD9 and CD63, enhanced productive particle transmission to
      target cells, suggesting additional roles for tetraspanins in the transmission
      process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T
      lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in
      order to maximize the efficiency of its transmission within the host. CONCLUSION:
      Altogether, these results establish an active role of tetraspanins in HIV-1
      producer cells.

PMID- 19602279
TI  - Novel transcriptional profile in wrist muscles from cerebral palsy patients.
AB  - BACKGROUND: Cerebral palsy (CP) is an upper motor neuron disease that results in
      a progressive movement disorder. Secondary to the neurological insult, muscles
      from CP patients often become spastic. Spastic muscle is characterized by an
      increased resistance to stretch, but often develops the further complication of
      contracture which represents a prominent disability in children with CP. This
      study's purpose is to characterize alterations of spastic muscle on the
      transcriptional level. Increased knowledge of spastic muscle may lead to novel
      therapies to improve the quality of life for children with CP. METHOD: The
      transcriptional profile of spastic muscles were defined in children with cerebral
      palsy and compared to control patients using Affymetrix U133A chips. Expression
      data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for
      select genes. Significant genes were determined using a 2 x 2 ANOVA and results
      required congruence between 3 preprocessing algorithms. RESULTS: CP patients
      clustered independently and 205 genes were significantly altered, covering a
      range of cellular processes. Placing gene expression in the context of
      physiological pathways, the results demonstrated that spastic muscle in CP adapts
      transcriptionally by altering extracellular matrix, fiber type, and myogenic
      potential. Extracellular matrix adaptations occur primarily in the basal lamina
      although there is increase in fibrillar collagen components. Fiber type is
      predominately fast compared to normal muscle as evidenced by contractile gene
      isoforms and decrease in oxidative metabolic gene transcription, despite a
      paradoxical increased transcription of slow fiber pathway genes. We also found
      competing pathways of fiber hypertrophy with an increase in the anabolic IGF1
      gene in parallel with a paradoxical increase in myostatin, a gene responsible for
      stopping muscle growth. We found evidence that excitation-contraction coupling
      genes are altered in muscles from patients with CP and may be a significant
      component of disease. CONCLUSION: This is the first transcriptional profile
      performed on spastic muscle of CP patients and these adaptations were not
      characteristic of those observed in other disease states such as Duchenne
      muscular dystrophy and immobilization-induced muscle atrophy. Further research is
      required to understand the mechanism of muscle adaptation to this upper motor
      neuron lesion that could lead to the development of innovative therapies.

PMID- 19602280
TI  - The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells.
AB  - BACKGROUND: Increased serum level of parathyroid hormone (PTH) was found in
      metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH
      expression, to suppress cell proliferation and to induce apoptosis in parathyroid
      cells. In this study, we investigated the effect of R-568 on cellular survival of
      prostate cancer cells. METHODS: Prostate cancer cell lines LNCaP and PC-3 were
      used in this study. Cellular survival was determined with MTT, trypan blue
      exclusion and fluorescent Live/Death assays. Western blot assay was utilized to
      assess apoptotic events induced by R-568 treatment. JC-1 staining was used to
      evaluate mitochondrial membrane potential. RESULTS: In cultured prostate cancer
      LNCaP and PC-3 cells, R-568 treatment significantly reduced cellular survival in
      a dose- and time-dependent manner. R-568-induced cell death was an apoptotic
      event, as evidenced by caspase-3 processing and PARP cleavage, as well as JC-1
      color change in mitochondria. Knocking down calcium sensing receptor (CaSR)
      significantly reduced R-568-induced cytotoxicity. Enforced expression of Bcl-xL
      gene abolished R-568-induced cell death, while loss of Bcl-xL expression led to
      increased cell death in R-568-treated LNCaP cells,. CONCLUSION: Taken together,
      our data demonstrated that calcimimetic R-568 triggers an intrinsic mitochondria
      related apoptotic pathway, which is dependent on the CaSR and is modulated by Bcl
      xL anti-apoptotic pathway.

PMID- 19602281
TI  - Regression based predictor for p53 transactivation.
AB  - BACKGROUND: The p53 protein is a master regulator that controls the transcription
      of many genes in various pathways in response to a variety of stress signals. The
      extent of this regulation depends in part on the binding affinity of p53 to its
      response elements (REs). Traditional profile scores for p53 based on position
      weight matrices (PWM) are only a weak indicator of binding affinity because the
      level of binding also depends on various other factors such as interaction
      between the nucleotides and, in case of p53-REs, the extent of the spacer between
      the dimers. RESULTS: In the current study we introduce a novel in-silico
      predictor for p53-RE transactivation capability based on a combination of
      multidimensional scaling and multinomial logistic regression. Experimentally
      validated known p53-REs along with their transactivation capabilities are used
      for training. Through cross-validation studies we show that our method
      outperforms other existing methods. To demonstrate the utility of this method we
      (a) rank putative p53-REs of target genes and target microRNAs based on the
      predicted transactivation capability and (b) study the implication of
      polymorphisms overlapping p53-RE on its transactivation capability. CONCLUSION:
      Taking into account both nucleotide interactions and the spacer length of p53-RE,
      we have created a novel in-silico regression-based transactivation capability
      predictor for p53-REs and used it to analyze validated and novel p53-REs and to
      predict the impact of SNPs overlapping these elements.

PMID- 19602282
TI  - Tolerability of breast ductal lavage in women from families at high genetic risk
      of breast cancer.
AB  - BACKGROUND: Ductal lavage (DL) has been proposed as a minimally-invasive, well
      tolerated tool for obtaining breast epithelial cells for cytological evaluation
      of breast cancer risk. We report DL tolerability in BRCA1/2 mutation-positive and
      -negative women from an IRB-approved research study. METHODS: 165 BRCA1/2
      mutation-positive, 26 mutation-negative and 3 mutation unknown women underwent
      mammography, breast MRI and DL. Psychological well-being and perceptions of pain
      were obtained before and after DL, and compared with pain experienced during
      other screening procedures. RESULTS: The average anticipated and experienced
      discomfort rating for DL, 47 and 48 (0-100), were significantly higher (p < 0.01)
      than the anticipated and experienced discomfort of mammogram (38 and 34), MRI (36
      and 25) or nipple aspiration (42 and 27). Women with greater pre-existing
      emotional distress experienced more DL-related discomfort than they anticipated.
      Women reporting DL-related pain as worse than expected were nearly three times
      more likely to refuse subsequent DL than those reporting it as the same or better
      than expected. Twenty-five percent of participants refused repeat DL at first
      annual follow-up. CONCLUSION: DL was anticipated to be and experienced as more
      uncomfortable than other procedures used in breast cancer screening. Higher
      underlying psychological distress was associated with decreased DL tolerability.

PMID- 19602284
TI  - Does hypoglycemia following a glucose challenge test identify a high risk
      pregnancy?
AB  - OBJECTIVE: An association between maternal hypoglycemia during pregnancy with
      fetal growth restriction and overall perinatal mortality has been reported. In a
      retrospective pilot study we found that hypoglycemia was linked with a greater
      number of special care/neonatal intensive care unit admissions and approached
      significance in the number of women who developed preeclampsia. That study was
      limited by its retrospective design, a narrow patient population and the
      inability to perform multivariate analysis because of the limitations in the data
      points collected. This study was undertaken to compare the perinatal outcome in
      pregnancies with hypoglycemia following a glucose challenge test (GCT) to
      pregnancies with a normal GCT. METHODS: Obstetric patients (not pre-gestational
      diabetics or gestational diabetes before 24 weeks were eligible. Women with a 1
      hour glucose < or = 88 mg/dL (4.8 m/mol) following a 50-gram oral GCT were
      matched with the next patient with a 1 hour glucose of 89-139 mg/dL. Pregnancy
      outcomes were evaluated. RESULTS: Over 22 months, 436 hypoglycemic patients and
      434 normal subjects were identified. Hypoglycemia was increased in women < 25 (p
      = 0.003) and with pre-existing medical conditions (p < 0.001). Hypoglycemia was
      decreased if pre-pregnancy BMI > or = 30 (p = 0.008).Preeclampsia/eclampsia was
      more common in hypoglycemic women. (OR = 3.13, 95% CI 1.51 - 6.51, p = 0.002) but
      not other intrapartum and perinatal outcomes. CONCLUSION: Hypoglycemic patients
      are younger, have reduced pre-pregnancy weight, lower BMIs, and are more likely
      to develop preeclampsia than normoglycemic women.

PMID- 19602285
TI  - Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role
      in malaria, sepsis, and leprosy.
AB  - BACKGROUND: The Toll-like receptors (TLRs) mediate innate immunity to various
      pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has
      recently been reported to be common in Europeans and Africans and to roughly half
      the risks of heterogeneous infectious diseases including malaria, tuberculosis,
      bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.
      METHODS: We assessed the TIRAP S180L variant by melting curve and RFLP analysis
      in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114
      individuals participating in case control studies on sepsis and leprosy in
      Germany, Turkey and Bangladesh. RESULTS: In Ghana, the TIRAP S180L polymorphism
      was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9%
      and 12% of German, Bangladesh and Turkish controls, respectively. No significant
      association of the heterozygous genotype with sepsis or leprosy was observed.
      Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the
      German study (P = 0.04). CONCLUSION: A broad protective effect of TIRAP S180L
      against infectious diseases per se is not discernible.

PMID- 19602283
TI  - Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian
      human immunodeficiency virus.
AB  - BACKGROUND: Although pig-tailed macaques (Macaca nemestrina) have been used in
      AIDS research for years, less is known about the early immunopathogenic events in
      this species, as compared to rhesus macaques (Macaca mulatta). Similarly, the
      events in early infection are well-characterized for simian immunodeficiency
      viruses (SIV), but less so for chimeric simian-human immunodeficiency viruses
      (SHIV), although the latter have been widely used in HIV vaccine studies. Here,
      we report the consequences of intrarectal infection with a CCR5-tropic clade C
      SHIV-1157ipd3N4 in pig-tailed macaques. RESULTS: Plasma and cell-associated virus
      was detectable in peripheral blood and intestinal tissues of all four pig-tailed
      macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed
      a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites,
      resulting in a marked decrease of CD4:CD8 T cell ratios 0.5-4 weeks after
      inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5
      coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the
      R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the
      acute phase seroconverted as early as week 4, with two developing cross-clade
      neutralizing antibody responses by week 24. These two animals also demonstrated
      persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as
      shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post
      inoculation. CONCLUSION: These findings indicate that SHIV-1157ipd3N4-induced
      pathogenesis in pig-tailed macaques followed a similar course as SIV-infected
      rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a
      useful and relevant model for AIDS vaccine and pathogenesis research.

PMID- 19602286
TI  - Genome wide analysis of human genes transcriptionally and post-transcriptionally
      regulated by the HTLV-I protein p30.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-I) is a human retrovirus
      that is etiologically linked to adult T-cell leukemia (ATL), an aggressive and
      fatal lymphoproliferative disease. The viral transactivator, Tax, is thought to
      play an important role during the initial stages of CD4+ T-cell immortalization
      by HTLV-1. Tax has been shown to activate transcription through CREB/ATF and NF
      KB, and to alter numerous signaling pathways. These pleiotropic effects of Tax
      modify the expression of a wide array of cellular genes. Another viral protein
      encoded by HTLV-I, p30, has been shown to affect virus replication at the
      transcriptional and posttranscriptional levels. Little is currently known
      regarding the effect of p30 on the expression and nuclear export of cellular host
      mRNA transcripts. Identification of these RNA may reveal new targets and increase
      our understanding of HTLV-I pathogenesis. In this study, using primary peripheral
      blood mononuclear cells, we report a genome wide analysis of human genes
      transcriptionally and post-transcriptionally regulated by the HTLV-I protein p30.
      RESULTS: Using microarray analysis, we analyzed total and cytoplasmic cellular
      mRNA transcript levels isolated from PBMCs to assess the effect of p30 on
      cellular RNA transcript expression and their nuclear export. We report p30
      dependent transcription resulting in the 2.5 fold up-regulation of 15 genes and
      the down-regulation of 65 human genes. We further tested nuclear export of
      cellular mRNA and found that p30 expression also resulted in a 2.5 fold post
      transcriptional down-regulation of 90 genes and the up-regulation of 33 genes.
      CONCLUSION: Overall, our study describes that expression of the HTLV-I protein
      p30 both positively and negatively alters the expression of cellular transcripts.
      Our study identifies for the first time the cellular genes for which nuclear
      export is affected by p30. These results suggest that p30 may possess a more
      global function with respect to mRNA transcription and the nuclear shuttling of
      cellular mRNA transcripts. In addition, these alterations in gene expression may
      play a role in cell transformation and the onset of leukemia.

PMID- 19602287
TI  - The interactome of the amyloid beta precursor protein family members is shaped by
      phosphorylation of their intracellular domains.
AB  - BACKGROUND: Brain tissue from patients with Alzheimer's disease has shown an
      increase of phosphorylation of Tyr-682, located on the conserved Y682ENPTY motif,
      and Thr-668 residues, both in the intracellular domain (AID) of amyloid beta
      precursor protein (APP), although the role of these two residues is not yet
      known. RESULTS: Here, we report that the phosphorylation status of Tyr-682, and
      in some cases Thr-668, shapes the APP interactome. It creates a docking site for
      SH2-domain containing proteins, such as ShcA, ShcB, ShcC, Grb7, Grb2, as well as
      adapter proteins, such as Crk and Nck, that regulate important biological
      processes, cytosolic tyrosine kinases, such as Abl, Lyn and Src, which regulate
      signal transduction pathways, and enzymes that control phosphatidylinositols
      levels and signaling, such as PLC-gamma. At the same time, it either reduces
      (like for JIP1, NUMB, NUMBL and ARH) or abolishes (like for Fe65, Fe65L1 and
      Fe65L2) binding of other APP interactors. Phosphorylation of Thr-668, unlike Tyr
      682, does not seem to affect APP's ability to interact with the various proteins,
      with Pin1 and X11 being the exclusions. We also found that there are some
      differences between the interactions to AID and to ALID1 and ALID2, its two
      homologues. CONCLUSION: Our data indicates that APP can regulate diverse cellular
      processes and that, vice versa, a network of signaling events can impact APP
      processing. Our results also suggest that phosphorylation of the APP
      Intracellular Domain will dramatically shape the APP interactome and,
      consequently, will regulate APP processing, APP transport and APP/AID-mediated
      functions.

PMID- 19602288
TI  - Mycobacterium avium subspecies paratuberculosis, Crohn's disease and the Doomsday
      scenario.
AB  - Johne's disease is chronic inflammation of the intestine caused by Mycobacterium
      avium subspecies paratuberculosis. Infection and disease are mainly in domestic
      livestock but can affect many species including primates. Johne's is a new
      disease which emerged at the turn of the 19th and 20th centuries and principally
      involved Europe and North America. It has since spread to former low incidence
      regions to become a global problem. Crohn's disease is a chronic inflammation of
      the intestine in humans which emerged in Europe and North America mid 20th
      century and increased to become a major healthcare problem. It has now spread to
      former low incidence regions. Infected animals shed Mycobacterium avium
      subspecies paratuberculosis in milk and into the environment. Human populations
      are widely exposed. Outcomes maybe influenced by microbial phenotype. Exposure to
      extracellular forms of these pathogens may confer some natural protection;
      exposure to intracellular forms which have passaged through milk macrophages or
      environmental protists may pose a greater threat to humans particularly
      individuals with an inherited or acquired susceptibility. Hot spots of human
      disease such as in Winnipeg which sits on rock at the junction of two rivers may
      result from local exposure to high levels of waterborne pathogens brought down
      from farmland. When appropriate methods are used most people with Crohn's disease
      are found to be infected. There are no data which demonstrate that these
      pathogens are harmless to humans. An overwhelming balance of probability and
      Public health risk favours the conclusion that Mycobacterium avium subspecies
      paratuberculosis is also pathogenic for people. A two tier co-operative
      pathogenic mechanism is proposed in Crohn's disease. Intracellular infection with
      the primary pathogen widely distributed throughout the gut causes an immune
      dysregulation and a specific chronic enteric neuropathy with loss of mucosal
      integrity. Segments of gross inflammatory disease result from the perturbed
      neuroimmune response to penetration into the gut wall of secondary pathogens from
      the lumen. These include both normal gut organisms and educated members of the
      enteric microbiome such as more aggressive E. coli. More new diseases may arise
      from failure to apply a range of remedial measures to this longstanding zoonotic
      problem.

PMID- 19602290
TI  - Patient experiences and health system responsiveness in South Africa.
AB  - BACKGROUND: Patients' views are being given more and more importance in policy
      making. Understanding populations' perceptions of quality of care is critical to
      developing measures to increase the utilization of primary health care services.
      Using the data from the South African World Health Survey (WHS), the current
      study aims to evaluate the degree of health care service responsiveness (both out
      patient and in-patient) and comparing experiences of individuals who used public
      and private services in South Africa. METHODS: A population-based survey of 2352
      participants (1116 men and 1236 women) was conducted in South Africa in 2003, the
      WHS - as part of a World Health Organization (WHO) project focused on health
      system performance assessment in member countries. RESULTS: Health care
      utilization was among those who attended in-patient care 72.2% attended a public
      and 24.3% a private facility, and of those who attended out-patient care 58.7%
      attended a public and 35.7% a private facility. Major components identified for
      out-patient care responsiveness in this survey were highly correlated with health
      care access, communication and autonomy, secondarily to dignity, confidentiality
      and quality of basic amenities, and thirdly to health problem solution. The
      degree of responsiveness with publicly provided care was in this study
      significantly lower than in private health care. Overall patient non
      responsiveness for the public out-patient service was 16.8% and 3.2% for private
      care. Discrimination was also one of the principal reasons for non-responsiveness
      in all aspects of provided health care. CONCLUSION: Health care access,
      communication, autonomy, and discriminatory experiences were identified as
      priority areas for actions to improve responsiveness of health care services in
      South Africa.

PMID- 19602289
TI  - The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is not
      appropriate for withholding surgery in high-risk patients with aortic stenosis: a
      retrospective cohort study.
AB  - BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE)
      is a widely used risk assessment tool in patients with severe aortic stenosis to
      determine operability and to select patients for alternative therapies such as
      transcatheter aortic valve implantation. The objective of this study was to
      determine the accuracy of the EuroSCORE in predicting mortality following aortic
      valve replacement (AVR). METHODS: The logistic EuroSCORE was determined for all
      consecutive patients that underwent conventional AVR between 1995 and 2005 at our
      institution. Provincial Vital Statistics were used to determine all-cause
      mortality. The accuracy of the prognostic risk prediction provided by logistic
      EuroSCORE was assessed by comparing observed and expected operative mortality.
      RESULTS: During the study period, a total of 1,421 patients underwent AVR
      including 237 patients (16.7%) that had a logistic EuroSCORE > 20. Among these
      patients, the mean predicted operative mortality was 38.7% (SD = 18.1). The
      actual mortality of these patients was significantly lower than that predicted by
      EuroSCORE (11.4% vs. 38.7%, observed/expected ratio 0.29, 95% CI 0.15-0.52, P <
      0.05). The EuroSCORE overestimated mortality within all strata of predicted risk.
      Although medium-term mortality is significantly higher among patients with
      EuroSCORE > 20 (log rank P = 0.0001), approximately 60% are alive at five years.
      CONCLUSION: Actual operative mortality in patients undergoing AVR is
      significantly lower than that predicted by the logistic EuroSCORE. Additionally,
      medium-term survival following AVR is acceptable in high-risk patients with
      EuroSCORE > 20. More accurate risk prediction models are needed for risk
      stratifying patients with severe aortic stenosis.

PMID- 19602292
TI  - Cross-packaging of genetically distinct mouse and primate retroviral RNAs.
AB  - BACKGROUND: The mouse mammary tumor virus (MMTV) is unique from other
      retroviruses in having multiple viral promoters, which can be regulated by
      hormones in a tissue specific manner. This unique property has lead to increased
      interest in studying MMTV replication with the hope of developing MMTV based
      vectors for human gene therapy. However, it has recently been reported that
      related as well as unrelated retroviruses can cross-package each other's genome
      raising safety concerns towards the use of candidate retroviral vectors for human
      gene therapy. Therefore, using a trans complementation assay, we looked at the
      ability of MMTV RNA to be cross-packaged and propagated by an unrelated primate
      Mason-Pfizer monkey virus (MPMV) that has intracellular assembly process similar
      to that of MMTV. RESULTS: Our results revealed that MMTV and MPMV RNAs could be
      cross-packaged by the heterologous virus particles reciprocally suggesting that
      pseudotyping between two genetically distinct retroviruses can take place at the
      RNA level. However, the cross-packaged RNAs could not be propagated further
      indicating a block at post-packaging events in the retroviral life cycle. To
      further confirm that the specificity of cross-packaging was conferred by the
      packaging sequences (psi), we cloned the packaging sequences of these viruses on
      expression plasmids that generated non-viral RNAs. Test of these non-viral RNAs
      confirmed that the reciprocal cross-packaging was primarily due to the
      recognition of psi by the heterologous virus proteins. CONCLUSION: The results
      presented in this study strongly argue that MPMV and MMTV are promiscuous in
      their ability to cross-package each other's genome suggesting potential RNA
      protein interactions among divergent retroviral RNAs proposing that these
      interactions are more complicated than originally thought. Furthermore, these
      observations raise the possibility that MMTV and MPMV genomes could also co
      package providing substrates for exchanging genetic information.

PMID- 19602291
TI  - Methylation and protein expression of DNA repair genes: association with
      chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas.
AB  - BACKGROUND: DNA repair genes critically regulate the cellular response to
      chemotherapy and epigenetic regulation of these genes may be influenced by
      chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to
      platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian
      carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115
      sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms
      collected after chemotherapy. Additionally, we assessed whether promoter
      methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or
      explained alterations in protein expression after chemotherapy exposure. RESULTS:
      Of 115 primary sporadic ovarian carcinomas, 39 (34%) had low BRCA1 protein and 49
      (42%) had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly
      concordant (p < 0.0001). MLH1 protein loss occurred in 28/115 (24%) primary
      neoplasms. BRCA1 protein loss in primary neoplasms was associated with better
      survival (p = 0.02 Log Rank test) and remained significant after accounting for
      either stage or age in a multivariate model (p = 0.04, Cox proportional hazards).
      In paired specimens, BRCA1 protein expression increased in 13/21 (62%) and BRCA2
      protein expression increased in 15/21 (71%) of recurrent carcinomas with low or
      intermediate protein in the paired primary. In contrast MLH1 expression was
      rarely decreased in recurrent carcinomas (1/33, 3%). Similar frequencies of MLH1,
      BRCA1, and FANCF promoter methylation occurred in primary carcinomas without
      previous chemotherapy, after neoadjuvant chemotherapy, or in recurrent neoplasms.
      CONCLUSION: Low BRCA1 expression in primary sporadic ovarian carcinoma is
      associated with prolonged survival. Recurrent ovarian carcinomas commonly have
      increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which
      could mediate resistance to platinum based therapies. However, alterations in
      expression of these proteins after chemotherapy are not commonly mediated by
      promoter methylation, and other regulatory mechanisms are likely to contribute to
      these alterations.

PMID- 19602293
TI  - New sources of soybean seed meal and oil composition traits identified through
      TILLING.
AB  - BACKGROUND: Several techniques are available to study gene function, but many are
      less than ideal for soybean. Reverse genetics, a relatively new approach, can be
      utilized to identify novel mutations in candidate genes; this technique has not
      produced an allelic variant with a confirmed phenotype in soybean. Soybean
      raffinose synthase genes and microsomal omega-6 fatty acid desaturase genes were
      screened for novel alleles in mutagenized soybean populations. RESULTS: Four
      mutations in independent lines were identified in the raffinose synthase gene
      RS2; two mutations resulted in amino acid mutations and one resulted in an
      altered seed oligosaccharide phenotype. The resulting phenotype was an increase
      in seed sucrose levels as well as a decrease in both raffinose and stachyose seed
      oligosaccharide levels. Three mutations in independent lines were identified in
      the omega-6 fatty acid desaturase gene FAD2-1A; all three mutations resulted in
      missense amino acid mutations and one resulted in an altered seed fatty acid
      profile that led to an increase in oleic acid and a decrease in linoleic acid in
      the seed oil. CONCLUSION: The oligosaccharide phenotype controlled by the novel
      RS2 allele is similar to previously observed seed oligosaccharide phenotypes in
      RS2 mutant (PI 200508) allele-containing lines. Due to the anti-nutritional
      characteristics of raffinose and stachyose, this represents a positive change in
      seed composition. The fatty acid phenotype controlled by the novel FAD2-1A allele
      controls an increase in oleic acid in the seed oil, a phenotype also observed in
      a line previously characterized to have a null allele of the FAD2-1A gene.
      Molecular marker assays were developed to reliably detect the inheritance of the
      mutant alleles and can be used in efficient breeding for these desired seed
      phenotypes. Our results serve as the first demonstration of the identification of
      soybean mutants controlling seed phenotypes discovered through the reverse
      genetics technique TILLING.

PMID- 19602294
TI  - Nucleation of protein aggregation kinetics as a basis for genotype-phenotype
      correlations in polyglutamine diseases.
AB  - Recent studies of inherited neurodegenerative disorders have suggested a linkage
      between the propensity toward aggregation of mutant protein and disease onset.
      This is particularly apparent for polyglutamine (polyQ) diseases caused by
      expansion of CAG-trinucleotide repeats. However, a quantitative framework for
      relating aggregation kinetics with molecular mechanisms of neurodegeneration
      initiation is lacking. Here, using the repeat-length-dependent age-of-onset in
      polyQ diseases, we derived a mathematical model based on nucleation of
      aggregation kinetics to describe genotype-phenotype correlations, and validated
      the model using both in vitro data and clinical data. Instead of describing polyQ
      aggregation kinetics with a derivative equation, our model divided age-of-onset
      (equivalent to the time required for aggregation) into two processes: nucleation
      lag time (a first-order exponential function of CAG-repeat length) and elongation
      time. With the exception of spinocerebellar ataxia (SCA) 3, the relation between
      CAG-repeat length and age-of-onset in all examined polyQ diseases, including
      Huntington's disease, dentatorubral-pallidoluysian atrophy and SCA1, -2, -6 and 
      7, could be well explained by three parameters derived from linear regression
      analysis based on the nucleated growth polymerization model. These parameters
      composed of probability of nucleation at an individual repeat, a protein
      concentration associated factor, and elongation time predict the overall features
      of neurodegeneration initiation, including constant risk for cell death, toxic
      polyQ species, main pathological subcellular site and the contribution of
      cellular factors. Our model also presents an alternative therapeutic strategy
      according to the distinct subcellular loci by the finding that nuclear
      localization of soluble mutant protein monomers itself has great impact on
      disease onset.

PMID- 19602295
TI  - Inconsistencies of genome annotations in apicomplexan parasites revealed by 5'
      end-one-pass and full-length sequences of oligo-capped cDNAs.
AB  - BACKGROUND: Apicomplexan parasites are causative agents of various diseases
      including malaria and have been targets of extensive genomic sequencing. We
      generated 5'-EST collections for six apicomplexa parasites using our full-length
      oligo-capping cDNA library method. To improve upon the current genome
      annotations, as well as to validate the importance for physical cDNA clone
      resources, we generated a large-scale collection of full-length cDNAs for several
      apicomplexa parasites. RESULTS: In this study, we used a total of 61,056 5'-end
      single-pass cDNA sequences from Plasmodium falciparum, P. vivax, P. yoelii, P.
      berghei, Cryptosporidium parvum, and Toxoplasma gondii. We compared these
      partially sequenced cDNA sequences with the currently annotated gene models and
      observed significant inconsistencies between the two datasets. In particular, we
      found that on average 14% of the exons in the current gene models were not
      supported by any cDNA evidence, and that 16% of the current gene models may
      contain at least one mis-annotation and should be re-evaluated. We also
      identified a large number of transcripts that had been previously unidentified.
      For 732 cDNAs in T. gondii, the entire sequences were determined in order to
      evaluate the annotated gene models at the complete full-length transcript level.
      We found that 41% of the T. gondii gene models contained at least one
      inconsistency. We also identified and confirmed by RT-PCR 140 previously
      unidentified transcripts found in the intergenic regions of the current gene
      annotations. We show that the majority of these discrepancies are due to
      questionable predictions of one or two extra exons in the upstream or downstream
      regions of the genes. CONCLUSION: Our data indicates that the current gene models
      are likely to still be incomplete and have much room for improvement. Our unique
      full-length cDNA information is especially useful for further refinement of the
      annotations for the genomes of apicomplexa parasites.

PMID- 19602297
TI  - Pest fruit fly (Diptera: Tephritidae) in northwestern Australia: one species or
      two?
AB  - Since 1985, a new and serious fruit fly pest has been reported in northwestern
      Australia. It has been unclear whether this pest was the supposedly benign
      endemic species, Bactrocera aquilonis, or a recent introduction of the
      morphologically near-identical Queensland fruit fly, B. tryoni. B. tryoni is a
      major pest throughout eastern Australia but is isolated from the northwest region
      by an arid zone. In the present study, we sought to clarify the species status of
      these new pests using an extensive DNA microsatellite survey across the entire
      northwest region of Australia. Population differentiation tests and clustering
      analyses revealed a high degree of homogeneity within the northwest samples,
      suggesting that just one species is present in the region. That northwestern
      population showed minimal genetic differentiation from B. tryoni from Queensland
      (FST=0.015). Since 2000, new outbreaks of this pest fruit fly have occurred to
      the west of the region, and clustering analysis suggested recurrent migration
      from the northwest region rather than Queensland. Mitochondrial DNA sequencing
      also showed no evidence for the existence of a distinct species in the northwest
      region. We conclude that the new pest fruit fly in the northwest is the endemic
      population of B. aquilonis but that there is no genetic evidence supporting the
      separation of B. aquilonis and B. tryoni as distinct species.

PMID- 19602298
TI  - Study on mating ecology and sex ratio of three internally ovipositing fig wasps
      of Ficus curtipes.
AB  - Studies on mating ecology and sex allocation in fig-parasitizing wasps
      ovipositing from outside the fig have given valuable insights into known factors
      that are responsible for the theory of sex ratio. Similarly, internally
      ovipositing fig-parasitizing wasps and fig-pollinating wasps provide interesting
      models for comparative analysis. In addition to the fig-pollinating wasp
      Eupristina sp., we found that Ficus curtipes hosts two species of internally
      ovipositing fig-parasitizing wasps: D. yangi and Lipothymus sp. Eupristina sp.
      males showed less aggression. Eupristina sp. has wingless males that mate only
      within the natal patch, providing excellent examples of full local-mate
      competition. D. yangi males showed high levels of aggression and lethal combat.
      D. yangi has winged males but mate mostly within the natal patch. Only a few
      matings occur after male dispersal. Its sex ratio was lower than the prediction
      of partial local mate competition theory. Wingless male Lipothymus sp., which
      mate partly after dispersal, did not present fatal fight. Therefore, the mating
      behaviour of D. yangi and Lipothymus sp. did not follow predicted patterns, based
      on wing morph. The mating pattern of D. yangi and Lipothymus sp. should follow
      the partial local mate competition theory. Furthermore, there was not a
      significant correlation between the proportion of males and the proportion of
      fruit parasitized in both winged D. yangi males and wingless Lipothymus sp.
      males.

PMID- 19602296
TI  - Erythropoietin overrides the triggering effect of DNA platination products in a
      mouse model of cisplatin-induced neuropathy.
AB  - BACKGROUND: Cisplatin mediates its antineoplastic activity by formation of
      distinct DNA intrastrand cross links. The clinical efficacy and desirable dose
      escalations of cisplatin are restricted by the accumulation of DNA lesions in
      dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We
      investigated in a mouse model by which mechanism recombinant erythropoietin
      (rhEPO) protects the peripheral nervous system from structural and functional
      damage caused by cisplatin treatment with special emphasis on DNA damage burden.
      RESULTS: A cumulative dose of 16 mg cisplatin/kg resulted in clear
      electrophysiological signs of neuropathy, which were significantly attenuated by
      concomitant erythropoietin (cisplatin 32,48 m/s +/- 1,68 m/s; cisplatin + rhEPO
      49,66 m/s +/- 1,26 m/s; control 55,01 m/s +/- 1,88 m/s; p < 0,001). The co
      application of rhEPO, however, did not alter the level of unrepaired cisplatin
      DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the
      sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and
      mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural
      injuries and resulted in an increased number of intact mitochondria. CONCLUSION:
      The protective effect of recombinant erythropoietin is not mediated by reducing
      the burden of DNA platination in the target cells, but it is likely to be due to
      a higher resistance of the target cells to the adverse effect of DNA damage. The
      increased frequency of intact mitochondria might also contribute to this
      protective role.

PMID- 19602299
TI  - Biennial hyperepidemic shigellosis in an observant Jewish community.
AB  - We aimed to study patterns of shigellosis in a large observant Jewish community
      in Israel and to describe local interventions during outbreaks. Surveillance data
      from the Ministry of Health were used to calculate incidence rates in 1998-2006,
      both in the city of Bene Beraq and the Tel Aviv district. Information on isolates
      was collected from the bacteriological laboratory of a community hospital. Public
      notices and educational conferences conveyed a message to increase personal
      hygiene and keep ill children at home. During a 9-year period, a clear biennial
      pattern of outbreaks was noticed. Annual incidence rates ranged between 18 and
      353/100,000 population. Shigellosis outbreaks tended to occur in the winter and
      were attributed to clonally related Shigella sonnei strains. Outbreaks in Bene
      Beraq preceded those in the other cities of Tel Aviv district, suggesting
      propagation of disease. In this population with highly endemic as well as
      superimposed outbreaks of shigellosis, short-term interventions had no lasting
      effect on prevention; future studies should focus on community-based programmes
      to avoid anticipated outbreaks.

PMID- 19602300
TI  - Analysis of phenotype, genotype and serotype distribution in erythromycin
      resistant group B streptococci isolated from vaginal flora in Southern Ireland.
AB  - The screening of 2000 women of childbearing age in Cork between 2004 and 2006
      produced 37 erythromycin-resistant group B streptococcus (GBS) isolates. PCR
      analysis was performed to determine the basis for erythromycin resistance. The
      ermTR gene was most frequently expressed (n = 19), followed by the ermB gene (n =
      8). Four isolates harboured the mefA gene. Six isolates yielded no PCR products.
      Some phenotype-genotype correlation was observed. All isolates expressing the
      mefA gene displayed the M phenotype whilst all those expressing ermB displayed
      the constitutive macrolide resistance (cMLS(B)) phenotype. Of 19 isolates that
      expressed the ermTR gene, 16 displayed the inducible macrolide resistance
      (iMLS(B)) phenotype. Serotype analysis revealed that serotypes III and V
      predominated in these isolates. The identification of two erythromycin-resistant
      serotype VIII isolates among this collection represents the first reported
      finding of erythromycin resistance in this serotype. A single isolate was non
      typable using two latex agglutination serotyping kits.

PMID- 19602301
TI  - Functional localization of the nitric oxide/cGMP pathway in the salamander
      retina.
AB  - Nitric oxide (NO) is a gaseous neuromodulator that has physiological functions in
      every cell type in the retina. Evidence indicates that NO often plays a role in
      the processing of visual information in the retina through the second messenger
      cyclic guanosine monophosphate (cGMP). Despite numerous structural and functional
      studies of this signaling pathway in the retina, none have examined many of the
      elements of this pathway within a single study in a single species. In this
      study, the NO/cGMP pathway was localized to specific regions and cell types
      within the inner and outer retina. We have immunocytochemically localized nitric
      oxide synthase, the enzyme that produces NO, in photoreceptor ellipsoids, four
      distinct classes of amacrine cells, Muller and bipolar cells, somata in the
      ganglion cell layer, as well as in processes within both plexiform layers.
      Additionally, we localized NO production in specific cell types using the NO
      sensitive dye diaminofluorescein. cGMP immunocytochemistry was used to
      functionally localize soluble guanylate cyclase that was activated by an NO donor
      in select amacrine and bipolar cell classes. Analysis of cGMP and its downstream
      target, cGMP-dependent protein kinase II (PKGII), showed colocalization within
      processes in the outer retina as well as in somata in the inner retina. The
      results of this study showed that the NO/cGMP signaling pathway was functional
      and its components were widely distributed throughout specific cell types in the
      outer and inner salamander retina.

PMID- 19602303
TI  - Cognitive recovery and predictors of functional outcome 1 year after traumatic
      brain injury.
AB  - Outcome studies on traumatic brain injury (TBI) have shown that functional status
      can be predicted by demographic, injury severity, and trauma-related factors.
      Concurrent cognitive functions as one of the determinants of functional outcome
      is less documented. This study evaluated the effects of concurrent
      neuropsychological measures on functional outcome 1 year after injury.
      Neuropsychological data, employment status, self-reported fatigue, and the
      Glasgow Outcome Scale-Extended (GOSE) were collected from 115 persons with TBI
      (ranging from mild to severe) at 3 and 12 months postinjury. Principal components
      analysis was conducted with the neuropsychological measures and three components
      emerged. Multiple regression analysis, controlling for demographic and injury
      severity related factors, was used to test the effects of cognitive components at
      12 months on functional outcome (GOSE). One year after injury, 64% were
      categorized as "good recovery" and 36% as "moderate disability" according to
      GOSE. Good functional recovery depended on shorter duration of posttraumatic
      amnesia, less fatigue, absence of intracranial pathology, higher education, and
      better performance on cognitive measures. The predictive values of
      Verbal/Reasoning and Visual/Perception components are supported; each added
      significantly and improved prediction of functional outcome. The Memory/Speed
      component showed a near-significant relationship to outcome.

PMID- 19602304
TI  - Improved visual sensitivity during smooth pursuit eye movements: temporal and
      spatial characteristics.
AB  - Recently, we showed that contrast sensitivity for color and high-spatial
      frequency luminance stimuli is enhanced during smooth pursuit eye movements
      (Schutz et al., 2008). In this study, we investigated the enhancement over a wide
      range of temporal and spatial frequencies. In Experiment 1, we measured the
      temporal impulse response function (TIRF) for colored stimuli. The TIRF for
      pursuit and fixation differed mostly with respect to the gain but not with
      respect to the natural temporal frequency. Hence, the sensitivity enhancement
      seems to be rather independent of the temporal frequency of the stimuli. In
      Experiment 2, we measured the spatial contrast sensitivity function for luminance
      defined Gabor patches with spatial frequencies ranging from 0.2 to 7 cpd. We
      found a sensitivity improvement during pursuit for spatial frequencies above 2-3
      cpd. Between 0.5 and 3 cpd, sensitivity was impaired by smooth pursuit eye
      movements, but no consistent difference was observed below 0.5 cpd. The results
      of both experiments are consistent with an increased contrast gain of the
      parvocellular retinogeniculate pathway.

PMID- 19602302
TI  - Receptive field properties of ON- and OFF-ganglion cells in the mouse retina.
AB  - There are two subclasses of alpha cell in the mammalian retina, which are
      morphologically identical in plain view but have opposite responses to a
      luminance change: one is ON center and the other is OFF center. Recent studies
      have shown that the neural circuitries, which underlie light responses in such ON
      and OFF-ganglion cell pairs, are not mirror symmetric with respect to the ON and
      OFF pathways (Pang et al., 2003; Zaghloul et al., 2003; Murphy & Rieke, 2006).
      This study examines alpha-cell homologues in the mouse retina and elucidates the
      synaptic mechanisms that generate their light responses. Morphological analysis
      of recorded cells revealed three subclasses that were essentially identical in
      plan view but had distinct vertical stratification levels. We refer to these
      cells as the sustained ON (ON-S), sustained OFF (OFF-S), and transient OFF (OFF
      T) cells (Murphy & Rieke, 2006; Margolis & Detwiler, 2007). Both ON-S and OFF-S
      cells were largely driven through the ON pathway via changes in excitatory and
      inhibitory inputs, respectively. Light responses of OFF-T cells were driven by
      transient changes in excitatory and inhibitory inputs. Light responses of OFF-S
      cells were also measured in connexin 36 knockout mice in order to dissect
      glycinergic input arising from AII amacrine cells. At photopic/mesopic
      intensities, peak glycinergic input to OFF-S cells in the connexin 36 knockout
      mouse was reduced by ~85% compared to OFF-S cells in the wild-type retina. This
      is consistent with the idea that AII cells receive their input from ON-cone
      bipolar cells through gap junctions and in turn provide glycinergic inhibition to
      OFF-S cells.

PMID- 19602305
TI  - What do community-dwelling people with dementia need? A survey of those who are
      known to care and welfare services.
AB  - BACKGROUND: The aging society will bring an increase in the number of people with
      dementia living in the community. This will mean a greater demand on care and
      welfare services to deliver efficient and customized care, which requires a
      thorough understanding of subjective and objective care needs. This study aims to
      assess the needs of community-dwelling people with dementia as reported by
      themselves and by their informal carers. The study also aims to give insight into
      the service use and gaps between needs and the availability of services. METHODS:
      236 community-dwelling people with dementia and 322 informal carers were
      interviewed separately. (Un)met needs were assessed using the Camberwell
      Assessment of Needs for the Elderly (CANE). RESULTS: Most unmet needs were
      experienced in the domains of memory, information, company, psychological
      distress and daytime activities. People with dementia reported fewer (unmet)
      needs than their carers. Type and severity of dementia, living situation and
      informal carer characteristics were related to the number of reported needs.
      CONCLUSIONS: This study showed a large number of unmet needs in dementia. Reasons
      for unmet needs are lack of knowledge about the existing service offer, a
      threshold to using services and insufficient services offer. These results
      provide a good starting point for improving community care for people with
      dementia.

PMID- 19602306
TI  - Improving care for patients with dementia hospitalized for acute somatic illness
      in a specialized care unit: a feasibility study.
AB  - BACKGROUND: Persons with dementia hospitalized for an acute illness have a high
      risk of poor outcomes and add to the burden on acute care systems. We developed a
      segregated Special Care Unit (SCU) in a somatic hospital for patients with
      challenging behavior resulting from dementia and/or delirium. This pilot study
      evaluates the feasibility and patient outcomes. METHODS: The SCU was established
      with environmental features that allow for safe and unrestricted ambulation
      within the unit and create a home-like atmosphere. Daytime activities structure
      the day and assure additional professional presence. The staff received intensive
      specialized training. Feasibility criteria were: acceptance by the staff,
      avoidance of transfers to geriatric psychiatry, lack of serious falls and
      mortality. Patient outcome criteria were ADL (Barthel index), mobility scores and
      behavior scores (Wilcoxon's, McNemar tests, pre-post design). RESULTS: 332
      consecutively admitted patients were enrolled. The SCU has been well received by
      the staff. Length of hospital stay did not differ from other hospital patients
      (15.3 +/- 8.3 vs. 15.0 +/- 10.3 days, p = 0.54). Six patients were transferred to
      geriatric psychiatry. Two patients suffered a fall-related hip fracture. The
      median Barthel Index improved significantly (admission 30, discharge 45, p <
      0.001), with only 8.5% of patients suffering functional loss. Wandering,
      aggression and agitation were significantly reduced (p < 0.001). CONCLUSIONS: The
      SCU has improved the care of patients with challenging behavior. Decline in ADL
      function and institutionalization occurred to a lesser degree than would be
      expected in this group of patients. Despite the selection of patients with
      behavioral problems, transfer to psychiatry was rare.

PMID- 19602307
TI  - Dementia knowledge among general practitioners: first results and psychometric
      properties of a new instrument.
AB  - BACKGROUND: General practitioners (GPs) play an important role in dementia care.
      Sufficient knowledge is one of the prerequisites for adequate dementia
      management, and educational activities do include knowledge transfer. There is no
      up-to-date measure of GPs' knowledge of dementia, resulting in the use of
      unreliable ad hoc questionnaires in recent studies, thus increasing the risk of
      biased results. METHODS: In a cross-sectional, observational questionnaire study,
      292 German GPs answered 37 questions regarding factual dementia knowledge. For
      the purpose of cross-validation, the psychometric properties of the test and its
      associations with GP characteristics were analyzed in independent samples with
      item and regression analyses. RESULTS: Twenty questions constituted a reliable
      questionnaire (Cohen's alpha = 0.733) with a normal distribution of test scores.
      Linear regression analysis revealed significant associations of the knowledge
      test score with the GPs' age and their attitudes towards dementia. CONCLUSIONS:
      The newly developed dementia-knowledge test for GPs can be used in observational
      studies, in which a rough and easy to use instrument is required.

PMID- 19602308
TI  - Immunogenicity and antigenicity of the recombinant EMA-1 protein of Theileria
      equi expressed in the yeast Pichia pastoris.
AB  - The equine piroplasmosis caused by Theileria equi is one of the most important
      parasitic diseases of the equine, causing damage to animal health and economic
      losses. In T. equi, 2 merozoite surface proteins, equi merozoite antigen EMA-1
      and EMA-2, have been identified as the most immunodominant antigens. This
      suggests that these antigens might be used as immunobiological tools. The EMA-1
      of Theileria equi was cloned and expressed in the yeast Pichia pastoris. The
      transformed yeast was grown at high cell density, expressing up to 389 mg x L(-1)
      of recombinant protein. The protein was concentrated and detected in Dot blot.
      The recombinant product was antigenically similar to the native protein as
      determined using monoclonal antibodies, and polyclonal antibodies obtained from
      equines naturally infected with T. equi. The immunogenicity of rEMA-1 protein was
      demonstrated by IFAT using sera from recombinant-protein-immunized mice using
      aluminum hydroxide as adjuvant. All animals vaccinated with rEMA-1 developed a
      high specific antibody response. This results suggest that rEMA-1 expressed in P.
      pastoris might be a strong candidate to be used as an antigen for immune
      diagnostics as well as a vaccine antigen.

PMID- 19602309
TI  - [Cloning, expression, molecular characterization of the MSP5 protein from PR1
      strain of Anaplasma marginale and its application in a competitive enzyme-linked
      immunosorbent test].
AB  - A competitive enzyme-linked immunosorbent test using the PR1 recombinant major
      surface protein 5 (rMSP5-PR1-ELISA) of Anaplasma marginale was standardized and
      validated using sera from anaplasmosis free and endemic regions. The sequencing
      of the msp5 gene of PR1 isolate showed 98% of identity with the Florida and Saint
      Maries isolates, 97% with Brazil (Pernambuco) and Havana isolates; and 91% with
      A. centrale. The cELISA-PR1 test was compared to IFI and cELISA-USA. For the
      standardization and validation of the cELISA-PR1, 380 bovine sera were used,
      whereas 245 truly positives and 135 truly negatives sera tested by the cELISA
      USA. In the standardization of the cELISA-PR1 135 negative and 148 positive
      bovine sera were used. The cELISA-PR1 and IFI tests showed 100 and 99.3%
      specificity, 100 and 98%, sensibility, and a kappa coefficient of 0.993 and
      0.978, respectively. For test validation, 245 bovine sera from an anaplasmosis
      endemic area were analyzed by the cELISA-PR1 and IFI, which showed 96.7 and 69.1%
      specificity, 98.9 e 96.3% sensibility and kappa coefficient of 0.956 and 0.699,
      respectively. These results indicate that the cELISA-PR1, likewise the cELISA
      USA, could sensitively and specifically detect cattle naturally infected with A.
      marginale and would be recommended for epidemiological studies, eradications
      program, and regulation of international cattle movement, while IFI, which
      presented lower specificity should not be used in situations that demand more
      specific diagnosis.

PMID- 19602310
TI  - New data on some species of Monogenea and Digenea parasites of marine fish from
      the coast of the State of Rio de Janeiro, Brazil.
AB  - Fifty four specimens of marine fish belonging to seven species collected from the
      coast of the State of Rio de Janeiro, Brazil were examined for helminths, and
      results relating to Monogenea and Digenea are presented. The monogeneans
      Metamicrocotyla macracantha, Microcotyle pomatomi and Gotocotyla acanthura are
      reported in new hosts. The digeneans Parahemiurus merus, Lecithochirium
      microstomum, Gonocercella pacifica, Aponurus laguncula, Gonocerca trematomi and
      Lampritrema miescheri are reported in new hosts, and the latter two species are
      also reported for the first time in Brazil.

PMID- 19602311
TI  - Comparison of indirect ELISA based on recombinant protein NcSRS2 and IFAT for
      detection of Neospora caninum antibodies in sheep.
AB  - Neospora caninum, an Apicomplexan parasite that can causes abortion, is
      responsible for considerable economic and reproductive losses in livestock. The
      purpose of the present study was to determine whether recombinant NcSRS2 is a
      suitable indirect ELISA antigen for determining specific immune response to N.
      caninum in sheep. A total of 441 serum samples were subjected to IFAT and rNcSRS2
      based-ELISA, with both tests performing similarly. The sensitivity and
      specificity of indirect ELISA were 98.6 and 98.3%, respectively. The kappa index
      shows 0.98 concordance between the two tests, which is considered excellent.
      Seroprevalences of 30.8 and 32.0% were detected by IFAT and indirect ELISA,
      respectively, showing these tests did not differ significantly on this measure (p
      > 0.05). Serological analysis showed that HisG tag was detected by Western
      Blotting recognizing rNcSRS2 protein. The potential value of rNcSRS2-based ELISA
      as a highly specific and sensitive tool for serological diagnosis is also
      supported by the strong agreement found between IFAT and ELISA. The results
      support the potential use of recombinant protein NcSRS2 as an antigen in indirect
      ELISA in sheep.

PMID- 19602312
TI  - Babesia spp. infection in dogs from rural areas of Sao Paulo State, Brazil.
AB  - The status of Babesia spp. infection in dogs from rural areas of Sao Paulo State,
      Brazil was studied. For this, 150 animals were examined by blood smears and by
      PCR; the presence of tick infestation was also investigated. By the blood smear
      examination, 3 animals (2%) were detected positive and by PCR for Babesia spp. 12
      (8%) were positive, with bands visualized in 450 bp. Rhipicephalus sanguineus or
      Amblyomma spp. were found on 36 (24%) of the 150 dogs. Amblyomma species found
      were A. cajennense (9/36-25%) and A. ovale (9/36-25%). It was not possible to
      correlate the presence of R. sanguineus and the infection with Babesia spp. The
      sequencing of four positive samples demonstrated close identity with B. canis
      vogeli already characterized in Brazil.

PMID- 19602313
TI  - Occurrence of Fasciola hepatica (Linnaeus, 1758) infection in Brazilian cattle of
      Minas Gerais, Brazil.
AB  - Fasciolosis is a parasitic disease which is caused by digenetic trematodes, such
      as Fasciola hepatica, and which occurs worldwide. The disease causes significant
      economic losses in cattle because of the reduction in milk and meat production
      and because the parasitized livers have no economic value. Also, abortion and
      mortality rates increase. To determine the occurrence and dispersal of F.
      hepatica in the state of Minas Gerais, fecal samples were collected from bovines
      aged 12 months and older between April 2005 and April 2006. The bovines came from
      1,251 rural farms of 120 municipalities/cities in Minas Gerais. Water was
      collected to ascertain the presence of the intermediate host in the properties
      where infected bovines were found. A total of 16 municipalities had infected
      bovines and 13 had the presence of Lymnaea columella. We detected infected
      bovines in 70% of the rural farms visited in the municipality of Itajuba. Itajuba
      was also found to have infected snails with the larval stage of F. hepatica. The
      results revealed that infection by F. hepatica in bovines of Minas Gerais was
      associated with the presence of the intermediate host and favorable
      epidemiological factors, drawing attention to the necessity of adopting proper
      control measures in the area.

PMID- 19602314
TI  - [Development and migration of cyathostome infective larvae (Nematoda:
      Cyathostominae) in bermuda grass (Cynodon dactylon) in tropical climate, in
      Baixada Fluminense, RJ, Brazil].
AB  - A study following the development and migration of Cyathostominae infective
      larvae was conducted from July 2003 to November 2004 in tropical climate, Baixada
      Fluminense, RJ, Brazil. Samples of naturally infected feces were placed on 12 m2
      plot each month on a cyathostomin-free "Bermuda grass" pasture (Cynodon
      dactylon). After Seven days, samples of feces and grass were collected every week
      at 8 a.m, 1 and 5 p.m., weighed and processed by Baermann technique. Higher
      survival of L3 was found at dry season, 15 and 12 weeks on feces and sward
      respectively, at rainy season the survival was smaller. The multivariable
      analysis of main components was evident the influence of time and environment
      variables on L3 recovery from feces and grass. Close relationship between time
      and the number of L3 in feces could be noted, in contrast with L3 in sward. The
      climatic conditions influenced directly the number of infective larvae. The
      infective larvae were recovered during three times and the Kruskal-Wallis test
      did not present significance among them.

PMID- 19602315
TI  - [The role of Ancyrocephalinae (Monogenea: Dactylogyridae), parasite of Geophagus
      brasiliensis (Pisces: Cichlidae), as an environmental indicator].
AB  - The variations in the parasite population of fishes may be indicative of
      environmental alterations. With the aim of studying the variation of the
      parasitism by Ancyrocephalinae in Geophagus brasiliensis, two reservoirs of
      distinct trophic characterizations (Juqueri - eutrophic and Jaguari -
      oligomesotrophic) were compared. The prevalence rates and intensity of infection
      of this parasite were measured bimonthly for one year. The results showed that
      the prevalence and the intensity of infection vary in according to the alteration
      in the storage level of the reservoirs and consequently to the variations in the
      amount of material in suspension in the water.

PMID- 19602316
TI  - [Prevalence of antibodies anti-Toxoplasma gondii in slaughtered cattle at
      stockyards in the State of Bahia, Brazil].
AB  - Serum samples of 600 slaughtered cattle from Ilheus and Itabuna Municipal
      slaughterhouse and Jequie Federal slaughterhouse, all of them located in the
      State of Bahia were screened using an indirect immunofluorescent antibody test
      against Toxoplasma gondii. Prevalence was 11.83% (71), and positive samples were
      distributed as 19.3% (37) from Ilheus, 9.8% (21) from Itabuna and 6.8% (13) from
      Jequie slaughterhouses respectively. From positive cattle, 91.5% (65) had titles
      1:64, and 8.5% (6) had title 1:256. The majority of serum positive samples
      against T. gondii were related to animals from dairy farms which were slaughtered
      at municipality stockyards under municipal inspection in comparison with those
      slaughtered at Federal inspection which were related to beef cattle that were
      raised in farms extensively.

PMID- 19602317
TI  - [Occurrence of gastrointestinal parasites in fecal samples of cats in Andradina
      City, Sao Paulo].
AB  - The purpose of this study was to verify the occurrence of gastrointestinal
      parasites in fecal samples from cats of the Andradina city, SP. This work was
      carried out from March to November of 2007, and used 51 cats delivered to the
      Center of Zoonoses Control of that city. Techniques of Willis and Faust were used
      in the fecal examination and resulted in detection of Ancylostoma spp. in 96.1%
      of the animals; Toxocara spp. in 43.1%; Cystoisospora spp. in 43.1%; Dipylidium
      caninum in 21.6% and Giardia spp. in 5.9% samples. Cryptosporidium spp. oocysts
      were detected in 3.9% fecal samples by the use of malachite green negative stain.
      There was no significant association between the occurrence of endoparasites and
      consistency of fecal samples. The results confirm that these cats represent
      important hosts of parasites, some of those with high zoonotic potential.

PMID- 19602319
TI  - [Mutagenic occurrence in teleoginae of Rhipicephalus sanguineus from
      intradomiciliary environment at Rio de Janeiro city].
AB  - From material collected by into a residence house at Rio de Janeiro city, using
      an aspirator machine during four continues hours in all house, it was captured
      1,284 Rhipicephalus sanguineus including 289 females; one of them showed a
      mutagenic alteration like an asymmetry of opistosome, and monstrosity like a two
      anus. The first register of this phenomenon in R. sanguineus is reported.

PMID- 19602318
TI  - [Occurrence of ticks (Acari: Ixodidae) in the municipality of Goiatins,
      Tocantins].
AB  - Due to a suspected human case of Brazilian Lyme-like disease in the city of
      Goiatins, Tocantins State, an epidemiological survey was carried out in eight
      counties in this region during September 2007 and February 2008, where 1,890
      ticks were collected from domestic animals and from the environment. A total of
      eight tick species were identified: Rhipicephalus sanguineus, Rhipicephalus
      (Boophilus) microplus, Dermacentor nitens, Amblyomma cajennense, Amblyomma
      oblongoguttatum, Amblyomma ovale, Amblyomma parvum and Amblyomma tigrinum. The
      last four species were described for the first time in this region. Although
      human parasitism by ticks is frequently described in Goiatins, no ticks collected
      from humans were analyzed. The study of ixodids in this region contributes with
      the survey of Brazilian ticks, as well as the elucidation of the possible
      transmission of the agent that caused the Brazilian Lyme-like disease case in
      Goiatins.

PMID- 19602320
TI  - [Chronic infection due to Toxoplasma gondii inducing neuron hypertrophy of the
      myenteric plexus of Rattus norvegicus descending colon].
AB  - The effects of the chronic infection due to Toxoplasma gondii tachyzoites on the
      myenteric neurons of the adult rat descending colon were assessed in this study.
      Ten male, 60-day-old, Wistar rats, divided into control and experimental group
      were orally inoculated with 105 tachyzoites from Toxoplasma gondii genotype I
      strain. After 30 days, the animals were anesthetized and submitted to laparotomy.
      The descending colon was removed, dissected, and the whole-mounts were staining
      by Giemsa, in order to observe neurons of the myenteric plexus, followed by
      quantitative and morphometric analysis. It was verified that the infection caused
      alterations neither with respect to the dimensions of the organ nor the neuronal
      population; however, there was a significant increase of the perikarion area and
      the cytoplasm.

PMID- 19602321
TI  - ACCOMPLISH the goal: hypertension and beyond.

PMID- 19602322
TI  - The SANDS randomized trial.

PMID- 19602324
TI  - Choosing the ideal drug for hypertension after ischemic stroke.
AB  - Controlling hypertension is known to be the most important treatment in
      preventing stroke. The past decade has been spent in debate over which class of
      hypertensive medication is most effective. This article reviews the studies
      assessing the efficacy of each agent class in secondary stroke prevention. The
      comparison of studies and agents is often difficult because of differences in
      achieved blood pressures and in the exact agents and combinations of agents that
      are used. Meta-analysis has attempted to resolve some of these difficulties by
      using meta-regression modeling to predict "expected" risk reduction given an
      achieved blood pressure. The resultant ability to give a value to "blood pressure
      independent" effects is questioned. The effect of reducing blood pressure far
      outweighs any other effect in reducing stroke risk, and the agent that has been
      shown to be most consistently equal or superior to any agent compared with it has
      been amlodipine, a calcium-channel blocker.

PMID- 19602323
TI  - The role of peroxisome proliferator-activated receptor gamma in blood pressure
      regulation.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the
      nuclear hormone receptor superfamily. It is expressed in adipocytes, immune
      cells, and cardiovascular cells that include cardiomyocytes, endothelial cells,
      and smooth muscle cells. PPARgamma plays a role in regulating cellular anti
      inflammatory responses and is a mediator of insulin sensitization induced by
      thiazolidinediones, which also can reduce elevated blood pressure both clinically
      and experimentally. As a result, research regarding the role of PPARgamma in
      blood pressure homeostasis is ongoing. Recent studies have demonstrated that
      increases or decreases in blood pressure phenotype may be PPARgamma-dependent and
      involve a number of different signaling pathways. Furthermore, studies using
      PPARgamma mutant transgenic and knockout animal models provide further evidence
      regarding a role for endothelial-cell and vascular smooth muscle-cell PPARgamma
      in blood pressure regulation. However, there is a need for further research
      regarding PPARgamma--mediated mechanisms involved in maintaining physiologic
      control of blood pressure.

PMID- 19602326
TI  - The potential role of the angiotensin subtype 2 receptor in cardiovascular
      protection.
AB  - Advances in our knowledge of the renin-angiotensin system have led to better
      understanding of the mechanisms contributing to the development of
      cardiovascular, renal, and metabolic disorders. Similarly, the discovery of new
      components of this system offers opportunities to develop new therapeutic tools
      to manage these diseases. Angiotensin subtype 2 (AT2) receptor represents one of
      those components with the potential for improving cardiovascular protection.
      Current knowledge suggests that the AT2 receptor antagonizes the effects of the
      angiotensin subtype 1 receptor. AT2 receptor activation is linked to
      vasodilation, nitric oxide production, and antiproliferative and anti
      inflammatory effects. The role of the AT2 receptor in inducing natriuresis,
      inhibiting renin release, limiting atherosclerosis, and promoting remodeling
      after myocardial infarction is reviewed in this article.

PMID- 19602325
TI  - Antihypertensive drugs and central blood pressure.
AB  - Recent evidence suggests that central blood pressure is a more important
      determinant of cardiovascular risk than brachial pressure. Interestingly,
      antihypertensive drugs exert different effects on brachial and central pressure.
      Traditional beta-blockers, such as atenolol, appear to have an adverse impact on
      central pressure, despite lowering brachial pressure. This may help to explain
      the results of recent large outcome studies using atenolol. Further research is
      required to clarify whether other antihypertensive agents lower central pressure
      beyond the effects observed on brachial pressure.

PMID- 19602328
TI  - Treatment of hypertension in patients with peripheral arterial disease: an
      update.
AB  - Hypertension is a known risk factor for cardiovascular events, and recent data
      have pointed to peripheral arterial disease (PAD) as another strong risk factor;
      together, they cause a surprisingly high total risk. This review deals with the
      clinical management of this dangerous association. The ankle-brachial index helps
      in the diagnosis of PAD and the estimation of risk. To control risk, lifestyle
      adaptation is essential. There is no consensus on a first choice of
      antihypertensive drug. Arguments favor angiotensin-converting enzyme inhibitors,
      but most patients require several antihypertensive drugs to reach goal pressure
      (140/90 mm Hg or lower). Moreover, to control the risk of PAD, antiplatelet
      drugs, antihypertensive drugs, and statins are recommended.

PMID- 19602327
TI  - Antihypertensive treatment and stroke prevention: from recent meta-analyses to
      the PRoFESS trial.
AB  - Blood pressure control is the cornerstone of therapeutic interventions aimed at
      preventing first strokes and recurrent strokes. All antihypertensive drug classes
      may be useful in preventing cerebrovascular events, depending on their efficacy
      in lowering elevated blood pressure values and achieving blood pressure control.
      However, recent findings indicate that drugs acting on the renin-angiotensin
      system (-angiotensin-converting enzyme inhibitors and angiotensin II receptor
      blockers) may exert cerebrovascular protective effects in addition to blood
      pressure reduction. This article examines the cerebrovascular protection provided
      by antihypertensive drug treatment in the light of the results of recent meta
      analyses and of the findings of the Prevention Regimen for Effectively Avoiding
      Second Strokes (PRoFESS) trial.

PMID- 19602330
TI  - Therapeutic approaches to diastolic dysfunction.
AB  - Progressive abnormalities of passive stiffness or active relaxation of the
      myocardium that impair ventricular filling during diastole may be an important
      contributor to the development of heart failure in patients with preserved
      ejection fraction. In this review, we discuss the epidemiology and
      pathophysiology of diastolic dysfunction and heart failure with preserved
      ejection fraction, highlighting potential therapeutic approaches and exploring
      the limited available evidence base for improving clinical outcomes in patients
      with these challenging entities.

PMID- 19602329
TI  - Hypertension, dementia, and antihypertensive treatment: implications for the very
      elderly.
AB  - A wealth of longitudinal epidemiologic evidence links high blood pressure or
      hypertension to cognitive decline and incident dementia. Some (but not all)
      studies have suggested that antihypertensive treatment is beneficial, reducing
      risk of decline and dementia. There are plausible mechanisms to support the
      possibility that hypertension may increase the risk of dementia. There is also
      evidence suggesting that the two dementia types thought to be most common,
      Alzheimer's disease and vascular dementia, have overlapping risk factors. Seven
      placebo-controlled trials of antihypertensive treatment have assessed cognitive
      function, incident dementia, or both, with mixed outcomes. The Hypertension in
      the Very Elderly Trial (HYVET), despite showing reductions in mortality and
      stroke with active treatment, found no significant reduction of incident
      dementia, although the trial was stopped early. Meta-analyses used to explore
      this area further are inconclusive, and comparative trials are now required.

PMID- 19602331
TI  - Management of hypertension in hemodialysis patients.
AB  - Hypertension is very common in patients with chronic kidney disease and is
      present in most patients with end-stage renal disease (ESRD). Hypertension is
      largely responsible for premature cardiovascular disease in dialysis patients.
      The pathophysiology of hypertension in ESRD is complex, and multiple mechanisms
      are likely involved in blood pressure dysregulation in patients on hemodialysis.
      Some of these patients demonstrate resistant hypertension. Aggressive control of
      hypertension in ESRD/dialysis is mandatory. Generally, nonpharmacologic
      treatments are not enough to achieve the goal blood pressure levels in dialysis
      patients. Multiple antihypertensive drugs are often necessary. Drugs that block
      the renin-angiotensin system offer a number of advantages for patients with
      chronic kidney disease or ESRD, but additional drug classes are often needed to
      achieve effective blood pressure control in dialysis patients. Physicians
      treating hypertension in dialysis patients should be familiar with the
      pharmacokinetic properties of antihypertensive drugs in renal failure and choose
      the dosages accordingly. Vigorous control of hypertension is recommended to
      reduce the disease burden in patients with ESRD.

PMID- 19602333
TI  - Histologic evaluation of the depth of necrosis produced by argon beam
      coagulation: implications for use as adjuvant treatment of bone tumors.
AB  - Argon beam coagulation (ABC) has been advocated as adjuvant treatment after
      curettage of aggressive benign bone tumors. This study was done to evaluate the
      depth of necrosis in cancellous bone treated with ABC. A 6-month-old pig was
      sacrificed and 20 1.5-cm cortical windows were created in the metaphyseal areas
      of the humeri, femora, and tibiae, exposing the underlying cancellous bone. The
      defects were randomly assigned to four groups: A, control; B, ABC at 50 W; C, 100
      W; and D, 150 W. Histologic evaluation determined the depth of necrosis at each
      setting: A, 0.1 +/- 0.1 mm; B, 1.0 +/- 0.5 mm; C, 2.9 +/- 1.0 mm; and D, 4.2 +/-
      0.7 mm. There were statistically significant differences between each of the
      experimental groups and the control (p < .0001), between groups B and C (p <
      .0001), and groups C and D (p = .0002).

PMID- 19602332
TI  - Traumatic glenohumeral instability in athletes.
AB  - Traumatic glenohumeral instability represents a commonly encountered clinical
      scenario. Two case vignettes are presented along with an evidence-based review of
      epidemiology, pathophysiology, diagnosis, and treatment options.

PMID- 19602334
TI  - Are the relative indications for revision total knee arthroplasty changing?
AB  - There are relatively few data on the indications for revision total knee
      arthroplasty. The purpose of this study was to determine if the indications for
      revision have changed over the past decade. This is a retrospective review of
      demographic data and the indications for revision in two cohorts of patients by
      one surgeon. Patient gender, age, weight, time in situ, and reason for revision
      (eight categories) were recorded and analyzed by unpaired t-tests and chi-square
      tests. The first cohort was 81 revisions performed between 1990 and 1999. The
      second cohort was 116 revisions performed between 2000 and April 2008. There were
      no significant differences in the gender, mean age, mean weight, or mean time in
      situ between the two cohorts. There were more revisions for wear (p = .03) and
      instability (p = .06) in the recent cohort. There were significantly fewer
      revisions related to the patella prosthesis (p < .0001). There was no change in
      the number of revisions for infection between the two cohorts. The relative
      indications for revision total knee arthroplasty have changed over the past
      decade. Greater emphasis may be needed on improved balancing techniques to
      prevent instability and new bearing surfaces to decrease wear.

PMID- 19602335
TI  - Outcomes of posterior lumbar interbody fusion with the 9-mm width lumbar I/F cage
      and the variable screw placement system.
AB  - Posterior lumbar interbody fusion (PLIF) using interbody cages and posterior
      pedicle screw fixation has increased the successful fusion rate to nearly 100% in
      the lumbar spine. In the design of the cage, only the surface area of the opening
      for bone graft contact with the endplates varied with the width of the cage. When
      space is limited, the 9-mm width cages may be the largest size that can be used.
      Fusion is potentially compromised by the smaller surface area of bone graft. It
      is important to study the clinical and fusion success of these narrow cages. The
      authors report 90 patients who had PLIF with 9-mm Lumbar I/F Cages and pedicle
      screws. Minimum follow-up was 24 months (range, 2-5 years). Seventy-five patients
      (83%) had clinical success, and 15 (17%) were clinically unsuccessful. Fusion was
      successful in 82 patients (91.1%). Fusion success with the 9-mm cage was
      statistically lower than previously reported for the implant system as a whole (p
      = .0015). Mechanical failure did not occur with 9-mm cage usage.

PMID- 19602336
TI  - Sagittal plane balancing in the total knee arthroplasty.
AB  - Postoperative stiffness or instability may result from a total knee arthroplasty
      imbalanced in the sagittal plane. Total knee arthroplasty instrumentation systems
      differ in the basic strategies used to assure this balance. In an anterior
      referencing system, changes in femoral size affect flexion gap tightness, and
      femoral size selection is paramount to assure sagittal plane balance. Conversely,
      in posterior referencing systems, femoral size changes do not affect the flexion
      gap but, rather, influence femoral component-patella articulation.
      Flexion/extension gap systems use calibrated spacer blocks to ensure gap balance
      but do not guarantee midrange stability; if used incorrectly, they may cause
      component malposition and joint line elevation. The authors reviewed the
      strengths and weaknesses of system types and provided system-specific
      troubleshooting guidelines for clinicians addressing intraoperative sagittal
      plane imbalance.

PMID- 19602337
TI  - Unplanned surgical excision of extremity soft tissue sarcomas: patient profile
      and referral patterns.
AB  - Unplanned surgical excision of sarcomas remains a major treatment dilemma in the
      control of local disease. The purpose of this study is to develop a patient
      profile to identify patients at high risk for an unplanned excision. The study
      group consisted of 54 patients following an unplanned excision of a soft tissue
      sarcoma. The characteristics that were identified as high risk included the
      following: 20- to 40-year age range,>5 cm, trauma, and deep to fascia. It was
      common for the interpretation of imaging studies not to mention the possibility
      of sarcoma in the differential diagnosis. Patient referral was most commonly from
      general surgeons without specialty training in oncology. Orthopaedic surgeons
      should not rely solely on the radiologist's interpretation because they often
      lack clinical information necessary to direct them toward the diagnosis of
      sarcoma. This is particularly important in patients who are at high risk for
      unplanned excision as identified in this study. Unplanned excisions by
      nononcologic surgeons remain a problem; however, it appears that it is more
      prevalent in the general surgical community than in orthopaedics. This may be as
      a result of studies addressing this issue in orthopaedic journals, with emphasis
      of these articles at teaching institutions.

PMID- 19602338
TI  - Longitudinal and axial stability of a cementless metaphyseal versus a fully
      porous coated cylindrical femoral stem.
AB  - Immediate full weightbearing after total hip arthroplasty can potentially lead to
      faster recovery. This cadaver study demonstrated that a proximally coated taper
      stem and a fully porous coated cylindrical stem did not differ in axial and
      torsional stability at failure under simulated full weightbearing with force
      directed both along the stem axis and perpendicular to the plane of the
      prosthesis. Both the taper stem and the cylindrical stem showed adequate
      stability for an immediate weightbearing protocol with respect to gross failure
      in osteoporotic bone.

PMID- 19602339
TI  - Bimalleolar ankle fracture in an adolescent with tillaux fracture.
AB  - The purpose of this case report is to present an unusual fracture pattern in an
      11-year-old patient characterized by both a predominantly adult fracture type and
      an exclusively adolescent fracture type. The patient sustained a bimalleolar
      ankle fracture while sledding. A difficult to detect Tillaux fracture was
      discovered on preoperative radiograph. The fractures were operatively treated by
      open reduction and internal fixation. The fracture mechanism is most likely
      attributed to supination-external rotation injury. The patient thus far has no
      sign of permanent deformity or disability. This case is unique in that it
      illustrates an adult fracture type in an adolescent patient. The nearly hidden
      Tillaux fracture also emphasizes the importance of thorough radiographic
      examination of any fracture.

PMID- 19602341
TI  - [Antigenic cartography of influenza viruses].

PMID- 19602340
TI  - Partial fasciectomy for Dupuytren's contractures.
AB  - One hundred ninety-six patients with Dupuytren's contractures were treated by
      partial fasciectomy and adequate postoperative rehabilitation. All patients had
      flexion contracture of the proximal interphalangeal joint of >20 degrees ; 93
      patients had flexion contracture of the associated metacarpophalangeal joint of
      >30 degrees ; 143 patients had risk factors for Dupuytren's disease. Primary skin
      closure and splinting were done in all patients. Range of motion was begun by the
      1st week. Splinting was discontinued by the 2nd week, followed by night-time
      splinting until the 8th week. The mean follow-up was 6.6 years (range, 2-9
      years). At the latest examination, 72.5% of the patients had complete range of
      motion of the metacarpophalangeal and proximal interphalangeal joints; 20.2% had
      5 degrees -10 degrees of extension deficit and 7.3% had recurrent contractures of
      >20 degrees at the proximal interphalangeal joint and were subjected to
      reoperation. Complications included digital neurovascular injury in 5%, complex
      regional pain syndrome in 10.1%, and wound-healing problems and superficial
      infections in 15.1%.

PMID- 19602342
TI  - [Systems biology: from molecular networks to personalized medicine].

PMID- 19602343
TI  - [Occludin, an additional key for hepatitis C virus entry].

PMID- 19602344
TI  - [A new inflammatory pathway linked to NAD].

PMID- 19602345
TI  - [The profiling era: towards innovative approaches for tailored therapy].

PMID- 19602346
TI  - [New insight into the regulation of DNA nucleotide excision repair: implications
      for cancer development and treatment].

PMID- 19602347
TI  - [Ferritine, an old protein with novel attributes].

PMID- 19602348
TI  - [The controversial memory of natural killer cells?].

PMID- 19602349
TI  - [A novel strategy to design specific iNOS inhibitors].

PMID- 19602350
TI  - [AMP-activated protein kinase (AMPK) allows prolonged energy stockpile!].

PMID- 19602351
TI  - [Genetic compensation in human pathology].

PMID- 19602353
TI  - [Systemic biology, synthetic biology and nanobiotechnologies: the tryptic of the
      XXI th century].

PMID- 19602354
TI  - [Systems biology: from yesterday's concepts to tomorrow's discoveries].
AB  - The idea that genes and their products are the fundamental units of biology has
      profoundly influenced our scientific thinking during the second half of the past
      century. Today, this reductionism is challenged by a renaissance of a systems
      understanding of biology, focusing on the systems formed by interacting gene
      products rather than on individual gene products. This discipline, based on a
      complementary and more holistic approach, keeps expanding its scope thanks to
      biotechnological innovations as well as theoretical modeling. This review aims at
      showing how and why, since the beginning of the 21st century, in fundamental as
      well as biomedical research, systems biology is proving a promising paradigm for
      understanding emerging properties of complex biological systems.

PMID- 19602355
TI  - [Systems biology: the multiscale organization of living systems].
AB  - Complexity of biological systems originates not only from their emergent
      properties but also from the feedbacks exerted by these properties on elementary
      structures and mechanisms. A systemic approach is required to capture this
      multiscale organization and its among-level feedback loops which have resulted
      from selective pressure during evolution: the scientific challenge is not to take
      into account all the relevant details but rather to consider jointly several
      integration levels. New mathematical tools are necessary to express how the
      consistency and interrelations among these different levels control biological
      functions.

PMID- 19602356
TI  - [Medical applications of systems biology].
AB  - We illustrate in this review some applications of systems biology in the medical
      and biological areas. After a brief summary of time scales experienced by medical
      -observations and of the general scheme of dynamic systems, we describe how some
      techniques underlying the complex systems theory can be applied to model medical
      issues in immunology, medical genetics, developmental morphogenesis,
      biochemistry, epidemiology, telemedecine and multiple platforms of expertise. In
      concluding, we will discuss the issue of "clinomics" coupling clinical and -omics
      data in a unique patient-specific file.

PMID- 19602357
TI  - [Systems biology of cancer].
AB  - Cancer Systems Biology is now accepted and recognized as a promising field both
      in biological and clinical research. It relies on a rigorous formalization of
      regulation networks into precise and unambiguous languages. It provides both
      detailed and modular views of the complex biological system of interest (which in
      cancer research is typically an interaction network governing essential cellular
      events such as proliferation, differentiation, cell death...) in order to
      facilitate the interpretation of molecular profiles of tumors. The translation of
      these networks into mathematical models allows prediction of the evolution of the
      system in time and under certain perturbations. As a result, it can not only
      propose specific target points for pharmaceutical purposes, but also anticipate
      the evolution of tumors as well as their classifications. These characteristics
      emphasize the important role of Systems Biology of Cancer in the future of
      biomedical research.

PMID- 19602358
TI  - [Production and implementation of predictive biological models].
AB  - The production and implementation of methodologies allowing the construction of
      coherent, precise and trustworthy predictive biological models has become an
      inescapable necessity. The financial stakes -attached to this reality are very
      high indeed, be it in the public or the private domains (health, research, pharma
      and foodstuffs industries, environment, etc.). Modelling biological systems is
      widely presented as a problem in computational sciences. While certainly very
      true for low complexity, practically continuous systems, this view cannot be
      upheld in the case of discontinuous, hyper-complex systems such as living
      entities. In these domains, modelling becomes a problem in biology assisted by
      computational sciences and certainly not the obverse. The following article will
      attempt to demonstrate why it is so, using concrete examples.

PMID- 19602359
TI  - [Sorting, recycling and WNT signaling: Wntless and retromer functions].
AB  - Cell-cell signaling is essential for the development of multi-cellular organisms.
      Indeed, membrane traffic is required for the correct sorting and function of
      receptors and ligands. In the past decades, many genetic screens performed in C.
      elegans and Drosophila have been crucial to identify the role of intracellular
      traffic in signaling. In this review, we discuss recent work that led to the
      identification of Wntless, a sorting receptor for WNT, and of the retromer, a
      protein complex required for the recycling of Wntless from endosomes to the trans
      Golgi network.

PMID- 19602360
TI  - [Plasmodium vivax infection: not so benign].
AB  - Morbidity and mortality during malaria are mostly due to Plasmodium falciparum
      infection. However, it becomes clear that Plasmodium vivax is responsible for a
      dramatic toll in many endemic areas except Africa. Cerebral malaria, severe
      respiratory distress and severe anaemia were recently reported from different
      settings, with severe disease peaking at an earlier age than those of Plasmodium
      falciparum. Since infected red blood cells sequestration was not reported with
      Plasmodium vivax infection, mechanisms at the origin of these complications are
      still a mater of debate. The major issue addressed in that paper is to alert
      clinicians on the -potential severity of this "benign tertian fever".

PMID- 19602362
TI  - [Unambiguous identification of the remains of the Romanov family].
AB  - The human remains found in 1991 and in 2007 in Ekaterinburg (Russia) are
      identified as those of the Romanov imperial family. An accurate genomic analysis
      unambiguously documents this assertion.

PMID- 19602361
TI  - [Droplets and emulsions: very high-throughput screening in biology].
AB  - The combination of microfluidic manipulation of emulsion droplets and in vitro
      compartmentalization offers a means to parallelize biological and chemical assays
      in droplets. These droplets behave as independent microreactors that are
      produced, actuated and analyzed at rates of the order of 1000 droplets per
      seconds providing tools to parallelize assays on small volumes (pL to nL range)
      for high-throughput -screening: the throughput of the assays performed in
      droplets is 1000 times larger than the throughput of existing technologies, based
      on micromanipulation of liquid in microtitre plates by robotic devices. The
      droplet-based microfluidic technology enables controlled manipulation, analysis
      and sorting of cells, genes and macromolecules based on their enzymatic
      activities, as well as chemical compounds based on their activity on biological
      targets. The integration of microfluidic systems for a series of complex
      individual operations on droplets could offer a solution to the miniaturization
      and automation of biological assays, combined with a decrease of the assay
      volumes and an increase of throughput, going beyond the capacities of
      conventional screening systems.

PMID- 19602363
TI  - [Sir Francis Galton: the father of eugenics].
AB  - Not only was Sir Francis Galton a famous geographer and statistician, he also
      invented "eugenics" in 1883. Eugenics, defined as the science of improving racial
      stock, was developed from a new heredity theory, conceived by Galton himself, and
      from the evolution theory of Charles Darwin, transposed to human society by
      Herbert Spencer. Galton's eugenics was a program to artificially produce a better
      human race through regulating marriage and thus procreation. Galton put
      particular emphasis on "positive eugenics", aimed at encouraging the physically
      and mentally superior members of the population to choose partners with similar
      traits. In 1904, he presented his ideas in front of a vast audience of physicians
      and scientists in London. His widely-publicized lecture served as the starting
      point for the development of eugenics groups in Europe and the United States
      during the first half of the 20th century.

PMID- 19602364
TI  - [Everyman's sequence...].

PMID- 19602365
TI  - [Next-next gen sequencing, already...].

PMID- 19602366
TI  - [Cellular polyploidy in hepatic tissue: new role of insulin].

PMID- 19602377
TI  - Assessing gastrointestinal motility and disintegration profiles of magnetic
      tablets by a novel magnetic imaging device and gamma scintigraphy.
AB  - PURPOSE: To validate Magnetic Moment Imaging (MMI) for the investigation of
      gastrointestinal transit and disintegration of solid dosage forms and to
      correlate the MMI findings with the corresponding gamma scintigraphic data.
      MATERIALS AND METHODS: Three magnetic tablets (MTs) were investigated using in
      vitro and in vivo tests. The clinical study was a four-way, crossover study with
      the following arms: (a) immediate-release tablets administered in fasted state;
      (b) immediate-release tablets administered after 400mL of Clinutren ISO; (c)
      enteric-coated tablets administered in the fasted state; and (d) non
      disintegrating tablets studied in the lightly fed state (100mL of Clinutren ISO).
      RESULTS: In both the in vitro and in vivo studies, tablets were detected
      successfully by MMI and scintigraphy. There was a good correlation between
      gastric residence times and positional data (in the x, y and y, z-axes). In
      addition, MMI revealed early swelling behaviour of the tablet matrix. There was
      excellent agreement for the disintegration times of MT(A) in the fasted arm
      (scintigraphy 12.0+/-4.4min, MMI 11.8+/-4.4min). In the MT(A)-fed arm, onset
      times determined by scintigraphy were delayed in three subjects when compared to
      the corresponding MMI results. Delayed disintegration was observed with MT(A)
      administered after food (p<0.01) in both the techniques. CONCLUSION: The MMI
      device is a reliable imaging tool for tracking the transit and disintegration of
      a magnetic tablet through the gastrointestinal tract.

PMID- 19602384
TI  - GABAA receptor and cell membrane potential as functional endpoints in cultured
      neurons to evaluate chemicals for human acute toxicity.
AB  - Toxicity risk assessment for chemical-induced human health hazards relies mainly
      on data obtained from animal experimentation, human studies and epidemiology. In
      vitro testing for acute toxicity based on cytotoxicity assays predicts 70-80% of
      rodent and human toxicity. The nervous system is particularly vulnerable to
      chemical exposure which may result in different toxicity features. Acute human
      toxicity related to adverse neuronal function is usually a result of over
      excitation or depression of the nervous system. The major molecular and cellular
      mechanisms involved in such reactions include GABAergic, glutamatergic and
      cholinergic neurotransmission, regulation of cell and mitochondrial membrane
      potential, and those critical for maintaining central nervous system
      functionality, such as controlling cell energy. In this work, a set of chemicals
      that are used in pharmacy, industry, biocide treatments or are often abused by
      drug users are tested for their effects on GABA(A) receptor activity, GABA and
      glutamate transport, cell membrane potential and cell viability in primary
      neuronal cultures. GABA(A) receptor function was inhibited by compounds for which
      seizures have been observed after severe human poisoning. Commonly abused drugs
      inhibit GABA uptake but not glutamate uptake. Most neurotoxins altered membrane
      potential. The GABA(A) receptor, GABA uptake and cell membrane potential assays
      were those that identified the highest number of chemicals as toxic at low
      concentrations. These results show that in vitro cell assays may identify
      compounds that produce acute neurotoxicity in humans, provided that in vitro
      models expressing neuronal targets relevant for acute neural dysfunctions are
      used.

PMID- 19602387
TI  - Mammalian wildlife as complementary models in environmental neurotoxicology.
AB  - The purpose of this paper is to highlight the benefits of mammalian wildlife as
      models in environmental neurotoxicology. This is first addressed by discussing
      the general advantages of using mammalian wildlife as models, and highlighting
      how studies on mammalian wildlife can complement neurotoxicological studies in
      laboratory animals and humans. Second, specific examples are provided using three
      persistent, environmental contaminants of neurotoxic concern to humans, namely
      methylmercury (MeHg), polychlorinated biphenyls (PCBs), and polybrominated
      diphenyl ethers (PBDEs). Through these examples we show that studies on mammalian
      wildlife can provide important, real-world information on bioavailability,
      environmental exposures, early and sub-clinical effects (e.g., alterations in
      brain neurochemistry and neuroendocrine hormones), and clinical neurotoxicity
      (structural and functional damage). In many cases neurotoxicological outcomes are
      similar across mammalian species adding weight of evidence to causal
      relationships. Our review highlights that an opportunity exists to use mammalian
      wildlife to better understand the human health risks posed by environmental
      neurotoxicants.

PMID- 19602390
TI  - The molecular structures and expression patterns of zebrafish troponin I genes.
AB  - Troponin I (TnnI), a constituent of the troponin complex on the thin filament,
      providers a calcium-sensitive switch for striated muscle contraction. Cardiac
      TnnI is, therefore, a highly sensitive and specific marker of myocardial injury
      in acute coronary syndromes. The TnnI gene, which has been identified in birds
      and mammals , encodes the isoforms expressed in cardiac muscle fast skeletal
      muscle and slow skeletal muscle. However, very little is known about the TnnI
      gene in lower vertebrates. Here, we cloned and characterized the molecular
      structures and expression patterns of three types of zebrafish tnni genes: tnni1,
      tnni2, and tnn-HC (Heart and craniofacial). Based on the unrooted radial gene
      tree analysis of the TnnI gene among vertebrates, the zebrafish Tnni1 and TnnI2
      we cloned were homologous of the slow muscle TnnI1 and fast muscle TnnI2 of other
      vertebrates, respectively. In addition, reverse transcription-polymerase chain
      reaction (RT-PCR) and whole-mount in situ hybridization demonstrated that
      zebrafish tnni1 and tnni2 transcripts were not detectable in the somites until 16
      h post-fertilization (hpf), after which they were identified as slow-and fast
      muscle-specific, respectively . Interestingly, tnni-HC, a novel tnni isoform of
      zebrafish was expressed exclusive in heart during early cardiogenesis as 16 hpf,
      but then extended its expression in craniofacial muscle after 48 hpf. Thus, using
      zebrafish as our system model, it is suggested that the results, as noted above,
      may provide more insight into the molecular structure and expression pattens of
      the lower vertebrate TnnI gene.

PMID- 19602391
TI  - Expression of the apoptosis gene reaper in homeotic, segmentation and other
      mutants in Drosophila.
AB  - Apoptosis is an essential process required for development and morphogenesis in
      metazoan organisms. The apoptosis pathway and cell death machinery have been
      extensively studied, but little is known how apoptosis genes are regulated in the
      course of development . In this study, we analyzed the transcriptional regulation
      of the pro-apoptotic gene reaper (rpr) by performing whole-mount in situ
      hybridization in embryos mutant for a number of transcription factor genes in
      Drosophila melanogaster. In sum, our data show that all factors studied have very
      specific temporal and spatial effects on rpr transcription . Thus, our results
      reinforce the concept that apoptosis is an essential process for morphogenesis
      and that apoptosis related genes very tight developmental factors identified in
      sculpting the morphology of various embryonic structures by modulating the
      apoptosis pathway.

PMID- 19602392
TI  - Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear.
AB  - MicroRNAs (miRNAs) constitute a class of small non-coding endogenous RNAs that
      downregulate gene expression by binding to 3' untranslated region (UTR) of target
      messenger RNAs. Although they have been found to regulate developmental and
      physiological processes in several organs and tissues, their role in the
      regulation of the inner ear transcriptome remains unknown. In this report, we
      have performed systematic in situ hybridization to analyze the temporal and
      spatial distribution of three miRNAs (miR-96, mR-182, and mR-183) that are likely
      to arise from a single precursor RNA during the development and the maturation of
      the cochlea. Strikingly we found that the expression of mR-96, mR-182 and mR-183
      was highly dynamic during the development of the cochlea, from the patterning to
      the differentiation of the main cochlear structures.

PMID- 19602394
TI  - On the ultrastructure and functional morphology of the male chelicerae (gonopods)
      in Parasitina and Dermanyssina mites (Acari: Gamasida).
AB  - Males of Parasitina and Dermanyssina (Gamasida=Mesostigmata) have chelicerae
      modified to function as gonopods. The slit-like spermatotreme in the movable
      digit of the chela in males of Parasitina was studied in three species: in
      Pergamasus quisquiliarum and Holoparasitus sp. a rather simple slit is indeed
      present, whereas in Vulgarogamasus kraepelini the structure is represented by a
      fine duct traversing the movable digit. The spermatodactyl studied in two
      phytoseioid species (Phytoseiulus persimilis, Blattisocius dentriticus) of
      Dermanyssina is a slender process arising from the movable digit and containing a
      fine duct which is formed by cuticular folds. The spermatodactyl of these species
      thus differs remarkably from that described in Veigaia sp. The diversity of these
      structures seen in the few taxa studied up to now is discussed under functional
      and systematic aspects.

PMID- 19602393
TI  - Genomic mapping and expression patterns of C380, OK6 and D42 enhancer trap lines
      in the larval nervous system of Drosophila.
AB  - Since its description more than fifteen years ago, the GAL4-UAS system of
      heterologous transgenic expression has found universal and widespread use in
      Drosophila research , making it a uniquely powerful analytical tool. Several
      hundreds of enhancer-trap GAL4 "driver" lines have since been used to express
      proteins of interest in specific spatio-temporal domains. However, the identities
      of enhancer elements that regulate GAL4 expression in vivo are often not known.
      Here, I report the mapping of three GAL4 lines commonly used as motor neuron
      drivers. Sequencing of genomic DNA flanking these three P-element transposon
      insertion, C380, (BG380), OK6, and D42, shows that these insertions lie upstream
      of the futsch, Rapgap 1 and toll-6 gene, respectively . Of the three, OK6-GAL4
      (Rapgap 1) expression is most restricted to motor neurons, while C380-GAL4 and
      D42-GAL4 also show prominent expression in the peripheral nervous system,
      including body wall sensory nervous system. Albeit with clear differences.
      Finally, I test if the highly restricted expression pattern of Futsch is
      maintained in six other species of Drosophilids (D. yakuba, D. ananssae,
      D.pseudoobscura, D. dimulars, D. willistoni and D. virilis). My results suggest
      conserved control of Futsch expression across species, most likely through
      upstream cis-acting elements. A comparative anatomy of the laval central nervous
      systems and peripheral innervation in these Frosophilids species as revealed by
      contemporary immunohistochemical markers is also presented.

PMID- 19602395
TI  - The ultrastructural investigation of the midgut in the quill mite
      Syringophilopsis fringilla (Acari, Trombidiformes: Syringophilidae).
AB  - The midgut of the females of Syringophilopsis fringilla (Fritsch) composed of
      anterior midgut and excretory organ (=posterior midgut) was investigated by means
      of light and transmission electron microscopy. The anterior midgut includes the
      ventriculus and two pairs of midgut caeca. These organs are lined by a similar
      epithelium except for the region adjacent to the coxal glands. Four cell subtypes
      were distinguished in the epithelium of the anterior midgut. All of them
      evidently represent physiological states of a single cell type. The digestive
      cells are most abundant. These cells are rich in rough endoplasmic reticulum and
      participate both in secretion and intracellular digestion. They form
      macropinocytotic vesicles in the apical region and a lot of secondary lysosomes
      in the central cytoplasm. After accumulating various residual bodies and
      spherites, the digestive cells transform into the excretory cells. The latter can
      be either extruded into the gut lumen or bud off their apical region and enter a
      new digestive cycle. The secretory cells were not found in all specimens
      examined. They are characterized by the presence of dense membrane-bounded
      granules, 2-4 microm in diameter, as well as by an extensive rough endoplasmic
      reticulum and Golgi bodies. The ventricular wall adjacent to the coxal glands
      demonstrates features of transporting epithelia. The cells are characterized by
      irregularly branched apical processes and a high concentration of mitochondria.
      The main function of the excretory organ (posterior midgut) is the elimination of
      nitrogenous waste. Formation of guanine-containing granules in the cytoplasm of
      the epithelial cells was shown to be associated with Golgi activity. The
      excretory granules are released into the gut lumen by means of eccrine or
      apocrine secretion. Evacuation of the fecal masses occurs periodically. Mitotic
      figures have been observed occasionally in the epithelial cells of the anterior
      midgut.

PMID- 19602396
TI  - Fine structure of the antennal glands of the ant nest beetle Paussus favieri
      (Coleoptera, Carabidae, Paussini).
AB  - The antennae of the ant nest beetle Paussus favieri are studied by using both SEM
      and TEM. In the myrmecophilous genus Paussus, these structures are composed of
      three joints: scape, pedicel and a wide third joint, the "antennal club",
      resulting from the fusion of antennomeres A3-A11 (flagellum). The antennal club
      shows an exceptional glandular activity, with the presence of pores mostly
      crowded in special hairless cuticular areas, surrounding the base of single
      setae, grouped at the base of tufts of setae, or positioned inside deep pockets
      that store the secretions, with filiform material arising from them. The surface
      of A1 and A3 are covered by mechanoreceptors, modified to spread the glandular
      exudates, while the chemoreceptors are restricted to the apex of the club. The
      fine structural analysis shows a great number of antennal glands, that can be
      referred to three main typologies: type A (GhA) bi-cellular, composed of a large
      secretory cell and a small duct cell, positioned close to the antennal surface;
      type B (GhB), tri-cellular, composed of two secretory cells and one duct cell,
      less frequent and positioned deep inside the antennal club; type C (GhC), rare,
      located deeply within the antennal lumen, in the vicinity of the trophocytes.
      This complexity indicates that more than one substance could be released from the
      antennae. Possible functional aspects of the secretions dealing with symbiotic
      interaction with the host ants are discussed.

PMID- 19602407
TI  - Lichens.

PMID- 19602408
TI  - Semaphorin signalling.

PMID- 19602409
TI  - The cry embedded within the purr.

PMID- 19602410
TI  - Sex: deviant mating in yeast.
AB  - Recent comparative genomics and mutational studies of the genes regulating mating
      and meiosis in fungi provide new insights into not only the variability of the
      key genes, but also the plasticity of the regulatory circuitry in the evolution
      of mating systems.

PMID- 19602411
TI  - Animal communication: laughter is the shortest distance between two apes.
AB  - New acoustic analyses of the calls of great apes and humans in response to
      tickling reveal the probable evolutionary history of laughter in humans and our
      nearest living relatives, the great apes.

PMID- 19602412
TI  - Centrosomes: CNN's broadcast reaches the cleavage furrow.
AB  - Centrosomin (CNN), a core Drosophila centrosome protein, interacts with the newly
      identified protein Centrocortin to promote cleavage furrow formation in the early
      embryo. Significantly, this activity is distinct from CNN's well-established role
      in centrosome-based microtubule organization.

PMID- 19602413
TI  - Learning and memory: how sea slug behaviors become compulsive.
AB  - A recent study of how food-seeking behavior in the sea slug Aplysia becomes
      compulsive provides new insights into the neural mechanisms of operant
      conditioning.

PMID- 19602414
TI  - Cell-cycle control: don't supersize me.
AB  - Cells often grow to a certain cell size before entering mitosis and dividing. Two
      recent articles suggest that fission yeast cells sense their own size through the
      action of an intracellular gradient emanating from cell tips and a sensor at the
      cell middle.

PMID- 19602415
TI  - Genital evolution: the traumas of sex.
AB  - Copulating males usually insert their penis into the female and ejaculate in her
      reproductive tract; but in some species, males are more invasive, puncturing the
      female body-wall and inseminating directly into her body-cavity. A spider has
      just been added to this list and new perspectives provided on why males harm
      females during copulation in the first place.

PMID- 19602416
TI  - Second messenger signaling: multiple receptors for NAADP.
AB  - The second messenger NAADP appears to have an essential role as a universal
      trigger of Ca(2+) signaling. Following on from previously published NAADP
      receptor candidates, recent work now describes the identification of a novel
      NAADP-sensitive Ca(2+) channel.

PMID- 19602417
TI  - DNA repair: common approaches to fixing double-strand breaks.
AB  - In bacteria, the RecF pathway plays an important role in the repair of DNA breaks
      and gaps. Reconstitution of this reaction in vitro has revealed similarities with
      double-strand break repair in eukaryotes.

PMID- 19602419
TI  - Micropreparation of single secretory glands from the carnivorous plant Nepenthes.
AB  - A rapid mechanical micropreparation technique has been developed to isolate
      multicellular glands, here from Nepenthes pitchers, based on a microdissection
      platform. The method is an alternative to laser capture dissection because fresh
      plant tissue can be used directly without previous fixation. Subsequent
      experiments, such as polymerase chain reaction (PCR)-based detection of an
      individual gene encoding a thaumatin-like protein and RNA extraction for gene
      expression analysis, have been successfully added to prove the quality of the
      prepared biological material. The procedure described is adaptable to a broad
      range of plant species and should find wide application in the preparation of
      multicellular glands or other tissues.

PMID- 19602420
TI  - Expression artifact with retroviral vectors based on pBMN.
AB  - While characterizing various splice forms of p120 catenin, we observed what
      appeared to be a novel posttranslational modification of p120, resulting in a
      higher molecular weight form that was dependent on the splicing pattern. Further
      investigation revealed the higher molecular weight form to be a fusion protein
      between sequences encoded by the retroviral vector and p120. We found that the
      publicly available sequence of the vector we used does not agree with the
      experimental sequence. We caution other investigators to be aware of this
      potential artifact.

PMID- 19602421
TI  - Development of a charcoal paper adenosine triphosphate:pyrophosphate exchange
      assay: kinetic characterization of NEDD8 activating enzyme.
AB  - Ubiquitin activating enzyme (UAE, UBE1, or E1) and seven known homologous "E1s"
      initiate the conjugation pathways for ubiquitin and 16 other ubiquitin-like
      modifiers (ULMs) found in humans. The initial step catalyzed by E1s uses
      adenosine triphosphate (ATP) to adenylate the C terminus of the appropriate ULM
      and results in the production of inorganic pyrophosphate (PPi). The mechanism of
      these enzymes can be studied with assays that measure the rate of ULM-dependent
      ATP:PPi exchange. The traditional method follows the initial velocity of [32P]PPi
      incorporation into ATP by capturing the nucleotide on activated charcoal powder
      to separate it from excess [32P]PPi and then measuring [32P]ATP in a
      scintillation counter. We have modified the method by using charcoal paper to
      capture the nucleotide and a phosphorimager to quantify the [32P]ATP. The
      significant increase in throughput that these modifications provide is
      accomplished without any sacrifice in sensitivity or accuracy compared with the
      traditional method. To demonstrate this, we reproduce and extend the
      characterization of the NEDD8 activating enzyme.

PMID- 19602422
TI  - Differential effects of adenosine antagonists in two models of parkinsonian
      tremor.
AB  - Adenosine A(1) and A(2A) receptors are colocalized with dopamine D(1) and D(2)
      receptors on striatal projection neurons and adenosine antagonists have been
      proposed as adjunctive therapies to l-DOPA treatment in Parkinson patients. We
      present here two studies examining the effects of selective and non-selective
      adenosine antagonists in two rodent models of parkinsonian tremor. Tremulous jaw
      movements (TJMs) were induced by either the dopamine antagonist pimozide (1.0
      mg/kg) or the acetylcholine agonist tacrine (5.0 mg/kg), and were quantified by a
      trained observer who was blind to the treatment conditions. Animals were treated
      concomitantly with either caffeine (10.0 mg/kg non-selective adenosine
      antagonist), 8-cyclopentyltheophylline (CPT; 10.0 mg/kg; selective A(1)
      antagonist) or SCH58261 (8.0 mg/kg; selective A(2A) antagonist). Caffeine, CPT
      and SCH58261 all significantly reduced pimozide-induced TJM activity.
      Surprisingly administration of adenosine antagonists did not reduce tacrine
      induced TJMs, and in the case of SCH58261 significantly increased TJMs compared
      to tacrine alone. These results indicate that antagonism at A(1) receptors may be
      more important for the reduction of tremor than previously supposed. Furthermore
      they indicate that dopamine antagonist-induced tremor models and acetylcholine
      agonist-induced tremor models are not entirely similar, and caution should be
      taken when using these models to evaluate novel therapeutics.

PMID- 19602418
TI  - The primary cilium as a complex signaling center.
AB  - Respect for the primary cilium has undergone a remarkable renaissance over the
      past decade, and it is now thought to be an essential regulator of numerous
      signaling pathways. The primary cilium's functions range from the movement of
      cells and fluid, to sensory inputs involved with olfaction and photoreception.
      Disruption of cilia function is involved in multiple human syndromes collectively
      called 'ciliopathies'. The cilium's activities are mediated by targeting of
      receptors, channels, and their downstream effector proteins to the ciliary or
      basal body compartment. These combined properties of the cilium make it a
      critical organelle facilitating the interactions between the cell and its
      environment. Here, we review many of the recent advances contributing to the
      ascendancy of the primary cilium and how the extraordinary complexity of this
      organelle inevitably assures many more exciting future discoveries.

PMID- 19602423
TI  - Antibodies to calcium-binding S100B protein block the conditioning of long-term
      sensitization in the terrestrial snail.
AB  - The effects of antibodies to calcium-binding S100B protein diluted to 10(-12)
      (LAS100B) on the long-term sensitization in the Helix lucorum snail
      (neurobiological model of the anxious-depressive state) were evaluated. The
      administration of LAS100B prior to conditioning of long-term sensitization in the
      terrestrial snail 10 min prior to the first electric stimulus) prevents
      strengthening of the defensive reaction of withdrawing the ommatophores (eye
      tentacles) and the defensive reaction of closing the pneumostome. This effect is
      termed "protective", as it prevents the conditioning of long-term sensitization.
      At the same time, snails given an injection of saline developed long-term
      sensitization with a significant strengthening of the defensive reactions of
      withdrawing the ommatophores and closing the pneumostome. When LAS100B was
      administered before long-term sensitization in advance, the membrane and
      threshold potentials of premotor interneurons, which regulate defensive
      behaviour, decreased to a significantly lesser extent compared to the long-term
      sensitization arm. It is possible that the "protective" effect is linked to the
      mechanisms of maintaining the membrane potential and changes in extra- and
      intracellular balance of calcium-binding S100B protein.

PMID- 19602424
TI  - Effects of cannabinoid drugs on the reinforcing properties of food in
      gestationally undernourished rats.
AB  - Involvement of the endocannabinoids in hyperphagia has been demonstrated,
      however, behavioral characterization of its role in food reinforcement is
      limited. The present study investigated whether 2-arachidonoyl glycerol, an
      endocannabinoid ligand, and rimonabant, a CB1 antagonist, change the reinforcing
      properties of food in gestationally undernourished rats (a putative model of
      obesity) vs controls. Albino dams were food deprived by 0 to 45% of their free
      feeding weights up to day 18 of their gestational period. Their offspring were
      allowed to free-feed until postnatal day 75. Then, behavior of the offspring was
      placed under progressive ratio schedules of sucrose reinforcement. After baseline
      data were established, intraperitoneal injections of 2-AG (0.03-3.75 mg/kg), and
      rimonabant (SR141716, 0.3-3.0 mg/kg) were administered and compared across group.
      Results show gestationally undernourished (GU) rats as adults weighed less than
      controls at the time of testing and female offspring allowed to free-feed for
      over 35 weeks exhibited lower body weights than controls. Under baseline, GU rats
      had lower breakpoints than controls. 2-AG and rimonabant significantly increased
      and decreased, respectively, breakpoint and responses made per session,
      suggesting involvement of the cannabinoid system in food reinforcement. When
      comparing peak doses of 2-AG on breakpoint, gestationally undernourished rats
      exhibited lower peak doses than controls. These data suggest that under the
      gestation deprivation method employed, GU rats were thinner and had lower food
      reinforcer efficacy than controls, and may have heightened sensitivity to 2-AG.

PMID- 19602425
TI  - Endocannabinoids: friends and foes of reproduction.
AB  - Endocannabinoids are fatty acid amides like anandamide (AEA), and
      monoacylglycerols like 2-arachidonoylglycerol, that bind to cannabinoid,
      vanilloid and peroxisome proliferator-activated receptors. Their biological
      actions are controlled through not yet fully characterized cellular mechanisms.
      These compounds, together with their related enzymes, that include key proteins
      for the synthesis and degradation of endocannabinoids, cannabinoid and non
      cannabinoid receptors, and purported membrane transporter(s), form the
      "endocannabinoid system (ECS)". In the past few years AEA and related ECS
      elements have emerged as essential players in various aspects of human
      reproduction, both for males and females. Here, the key features of the ECS and
      the potential of its components to direct human fertility towards a positive or
      negative end will be reviewed. In particular, the involvement of AEA and related
      ECS elements in regulating embryo oviductal transport, blastocyst implantation
      and placental development (in females), and sperm survival, motility,
      capacitation and acrosome reaction (in males) will be addressed, as well as the
      role of endocannabinoids in sperm-oviduct interactions. Additionally, the
      possibility that blood AEA and its hydrolase FAAH may represent reliable
      diagnostic markers of natural and assisted reproduction in humans will be
      discussed, along with the therapeutic exploitation of ECS-oriented drugs as
      useful fertility enhancers.

PMID- 19602426
TI  - Platelet serotonin concentration and monoamine oxidase type B activity in female
      patients in early, middle and late phase of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder with
      unclear aetiology. Cognitive impairment in AD might be associated with altered
      serotonergic system. The aim of the study was to determine platelet serotonin (5
      HT) concentrations and platelet monoamine oxidase type B (MAO-B) activity in
      patients with different severity of AD. Platelet 5-HT concentrations and MAO-B
      activity were determined spectrofluorimetrically in 74 female patients with AD
      (NINCDS-ADRDA, DSM-IV-TR criteria), subdivided according to the Mini Mental State
      Examination (MMSE) scores in three groups with a) 23 patients in early (MMSE
      scores 19-24), b) 23 patients in middle (MMSE 10-18), and c) 28 patients in late
      (MMSE 0-9) phase of AD, and in 49 age-matched healthy women. Platelet 5-HT
      concentrations and MAO-B activity were similar between all patients with AD and
      healthy subjects, but were significantly lower in patients in the late phase of
      AD than in other phases of AD, and in healthy controls. The significant
      correlations were found between MMSE scores and platelet 5-HT concentrations, MAO
      B activity and age. Lower platelet 5-HT concentration and MAO-B activity in the
      late phase of AD suggested that these markers might indicate severity and/or
      clinical progress of AD.

PMID- 19602428
TI  - Minor genetic variants of the dopamine D4 receptor (DRD4) polymorphism are
      associated with novelty seeking in healthy Japanese subjects.
AB  - Although an association between the dopamine receptor D4 (DRD4) gene and
      personality traits had been previously investigated, results from previous
      studies were not conclusive. This may be due to the method of grouping used,
      which categorized the gene population into two groups based on the length of the
      variable number of tandem repeats (VNTR) in exon 3. In the present study, we
      categorized 616 healthy Japanese subjects into more than two groups by further
      subdividing the DRD4 48-bp VNTR polymorphism, and compared Temperament and
      Character Inventory (TCI) scores among the groups. A significant difference was
      found between the DRD4 48-bp VNTR polymorphism and novelty seeking (p=0.016). The
      novelty-seeking scores in the subjects carrying the 5/5 genotype were
      significantly higher than in those carrying the 2/2 genotype (p=0.002) or the 4/4
      genotype (p=0.005). However, when the conventional method of grouping was used
      (i.e., short alleles vs. long alleles), there were no significant associations
      between the DRD4 VNTR polymorphism and any TCI scores. Our results suggest that
      minor 5-repeat allele is associated with high novelty-seeking scores in healthy
      Japanese subjects.

PMID- 19602427
TI  - What is the bed nucleus of the stria terminalis?

PMID- 19602429
TI  - Linear and non-linear measures indicate gastric dysmotility in patients suffering
      from acute schizophrenia.
AB  - Cardiac autonomic dysfunction has been reported in patients suffering from
      schizophrenia. The aim of the present study was to evaluate gastric electrical
      activity in unmedicated patients suffering from acute schizophrenia in relation
      to their symptoms. Electrogastrography was performed before and after test meal
      ingestion in 26 patients suffering from schizophrenia and 26 matched controls.
      The non-linear measure approximate entropy (ApEn) was calculated for the first
      time from the obtained signal in addition to standardized measures. Results were
      correlated with the scales for the assessment of positive symptoms and negative
      symptoms. In addition, autonomic and abdominal symptoms were assessed by the
      autonomic symptom score. We found a significantly increased amount of
      tachygastria and arrhythmia within the signal of the activity of the gastric
      pacemaker before and after test meal digestion in patients compared to controls,
      indicating increased sympathetic modulation within the enteric nervous system. A
      significant difference was observed for slow wave, which represents the dominant
      frequency of gastric pacemaker activity, indicating gastric dysmotility in our
      patients. The elevated ApEn measure points to increased complexity and
      dysregulation. In addition, we have observed a correlation between delusions and
      tachygastria. Sympathetic function seems to be altered in the enteric nervous
      system of patients suffering from schizophrenia. Future studies need to explore
      the influence of the disease on different branches of the autonomic nervous
      system and clinical consequences of enteric dysfunction. Our findings point to a
      possible systemic autonomic imbalance that needs to be studied in respect to the
      neurobiology of schizophrenia.

PMID- 19602430
TI  - A diet rich in cocoa attenuates N-nitrosodiethylamine-induced liver injury in
      rats.
AB  - The effects of cocoa feeding against N-nitrosodiethylamine (DEN)-induced liver
      injury were studied in rats. Animals were divided into five groups. Groups 1 and
      2 were fed with standard and cocoa-diet, respectively. Groups 3 and 4 were
      injected with DEN at 2 and 4 weeks, and fed with standard and cocoa-diet,
      respectively. Group 5 was treated with DEN, received the standard diet for 4
      weeks and then it was replaced by the cocoa-diet. DEN-induced hepatic damage
      caused a significant increase in damage markers, as well as a decrease in the
      hepatic glutathione, diminished levels of p-ERK and enhanced protein carbonyl
      content, caspase-3 activity and values of p-AKT and p-JNK. The cocoa-rich diet
      prevented the reduction of hepatic glutathione concentration and catalase and GPx
      activities in DEN-injected rats, as well as diminished protein carbonyl content,
      caspase-3 activity, p-AKT and p-JNK levels, and increased GST activity. However,
      cocoa administration did not abrogate the DEN-induced body weight loss and the
      increased levels of hepatic-specific enzymes and LDH. These results suggested
      that cocoa-rich diet attenuates the DEN-induced liver injury.

PMID- 19602431
TI  - Increase in double-stranded DNA break-related foci in early-stage thymocytes of
      aged mice.
AB  - Cellular and molecular mechanisms involved in aging are notoriously complex.
      Aging-related immune decline of T lymphocyte function is partly caused by
      attrition of thymic T cell development, which involves programmed creation and
      repair of DNA breaks for generating T cell receptors. Aging also leads to
      significant alterations in the cellular DNA repair ability. We show that higher
      levels of gamma-phosphorylated H2AX (pH2AX), which marks DNA double-stranded
      breaks (DSBs), were detectable in early thymocyte subsets of aged as compared to
      young mice. Also, while only 1-2 foci of nuclear accumulation of pH2AX were
      detectable in these early thymocytes from young mice, cells from aged mice showed
      higher numbers of pH2AX foci. In CD4-CD8- double-negative (DN) thymocytes of aged
      mice, which showed the highest levels of DSBs, there was a modest increase in
      levels of the DNA repair protein MRE11, but not of either Ku70, another DNA
      repair protein, or the cell cycle checkpoint protein p53. Thus, immature
      thymocytes in aged mice show a marked increase in DNA DSBs with only a modest
      enhancement of repair processes, and the resultant cell cycle block could
      contribute to aging-related defects of T cell development.

PMID- 19602432
TI  - Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas
      2B.
AB  - In this study, the potentially harmful effect of the exposure to fumed and porous
      silicon dioxide (silica) nanoparticles was investigated using human bronchial
      epithelial cell, Beas-2B, with a focus on the involvement of oxidative stress as
      the toxic mechanism. Silica nanoparticles-induced oxidative stress was assessed
      by examining the formation of reactive oxygen species (ROS) and induction of
      antioxidant enzymes, such as superoxide dismutase (SOD) and heme oxygenase-1 (HO
      1). Subsequently, to understand the mechanism of nanoparticles-induced oxidative
      stress, the involvement of oxidative stress-responding transcription factors,
      such as, nuclear factor-kappaB (NF-kappaB) and nuclear factor-E2-related factor-2
      (Nrf-2), as well as the mitogen-activated protein (MAP) kinase signal
      transduction pathway were investigated. From the overall results, silica
      nanoparticles exerted toxicity via oxidative stress, which lead to the induction
      of HO-1 via the Nrf-2-ERK MAP kinase signaling pathway; cells exposed to porous
      silica nanoparticles showed a more sensitive response than those exposed to fumed
      silica. Nevertheless, the parameters tested were rather limited in terms of
      gaining a full understanding of the oxidative stress and cellular response due to
      exposure to silica nanoparticles. Further studies on the mechanism by which
      silica nanoparticles induce the Nrf-2-ERK MAP kinase pathway, to more clearly
      elucidate the silica-induced oxidative stress, as well as on the relationship
      between the physico-chemical properties of nanoparticles and their cytotoxicity
      are warranted to gain an understanding of the phenomenon of different
      sensitivities between porous and fumed silica.

PMID- 19602433
TI  - Cheminformatics based selection and cytotoxic effects of herbal extracts.
AB  - Bioinformatics and traditional medicine can be used in discovery and design of
      novel candidate drugs to efficient cancer chemotherapy. In this study, similarity
      search tools employed to screen and introduce novel herbs with antitumor
      property. Several novel herbs have been selected by using logical computational
      algorithms and assayed on six cancerous cell lines. Complementary assays involved
      hemolytic and antifungal MIC tests have been performed to determine selectivity
      and their biocompatibility with RBC of herbal extracts. Final findings may point
      at selective activity of herbal extracts Rheum ribes, Ficus bengalensis, Morus
      alba, Musa sapientum, Arnebia decumbens, Citrus limon, Fraxinus excelsior, Rumex
      acetosella, Arnebia echioides in inducing cytotoxicity on cancerous cell lines.
      In the present research, in vitro results confirmed predicted findings from our
      in silico work. Complementary assays including antifungal MIC and hemolytic tests
      were carried out also to determine selectivity of herbal extracts. Findings
      resulted from hemolytic test showed that candidate herbal extracts did not induce
      hemolysis similar to negative control, also antifungal test results indicated
      that six herbal extracts had antifungal activity in concentration of 250
      microg/ml.

PMID- 19602434
TI  - Antiproliferative and cytotoxic effects of sodium selenite in human colon cancer
      cells.
AB  - Sodium selenite has been reported to interfere with cell growth and proliferation
      and to induce cell death. Despite of our current knowledge, details about its
      effects on growth and behavior of colonocytes with differing p53 status remain
      unknown. In our study, we evaluated the antiproliferative, cell cycle specific
      and proapoptotic potential of sodium selenite in HCT-116 colorectal cells with
      wild type p53 and its isogenic control HCT-116-p53KO cell line. Cell
      proliferation in selenite-treated cells was followed by computer-enhanced time
      lapse videomicroscopy, by measuring protein content (Coomassie Brilliant Blue
      assay), metabolic activity (WST-1) and DNA synthesis (BrdU). Changes in cell
      cycle were determined by flow cytometry and Western blotting. Cell death was
      measured with the nuclear fragmentation assay and caspase-3 immunostaining. We
      show that sodium selenite inhibits the growth and proliferation of colon cancer
      cells in a time- and dose-dependent manner, with HCT-116 cells being more
      sensitive than HCT-116-p53KO cells. Moreover, upon sodium selenite treatment,
      there was a tendency for cells to accumulate at G2 phase which was accompanied by
      the increasing expression of cyclin B1, Cdc2 p34, p21 and the sub G1 fraction of
      the cell cycle. In addition, PARP and nuclear fragmentation and activation of
      caspase-3 were more profound in HCT-116 cells versus HCT-116-p53KO cells, thus
      indicating important role of p53 and dependent signaling in selenite-induced
      toxicity.

PMID- 19602435
TI  - The use of the SeDeM Diagram expert system to determine the suitability of
      diluents-disintegrants for direct compression and their use in formulation of
      ODT.
AB  - The new SeDeM Diagram expert system was used to analyze the suitability of 43
      excipients for direct compression with disintegrant properties from eight
      chemical families. The SeDeM Diagram expert system is a new method for use in
      tablet preformulation and formulation studies. It provides the profile of a
      substance in powder form in terms of its suitability for direct compression. This
      study, which was based on the current concept of "Quality by Design ICH Q8",
      evaluated the pharmacotechnical properties of disintegrants in powder form and
      selected the candidates that were most suitable for direct compression and their
      use in formulation of orally disintegrating tablets (ODT). To achieve this, each
      disintegrant and its chemical families were individually analyzed. It was
      concluded that nine disintegrants had an SeDeM value with the index of good
      compression (IGC) over 5. Most of these disintegrants were from the
      microcellulose family. Other disintegrants had indexes that were close to 5. It
      is assumed that these excipients can be used in direct compression, when they are
      added to other excipients.

PMID- 19602436
TI  - Magnetic resonance imaging of tablet dissolution.
AB  - Magnetic resonance imaging (MRI) is the technique of choice for measuring
      hydration, and its effects, during dissolution of tablets since it non-invasively
      maps (1)H nuclei associated with 'mobile' water. Although most studies have used
      MRI systems with high-field superconducting magnets, low-field laboratory-based
      instruments based on permanent magnet technology are being developed that provide
      key data for the formulation scientist. Incorporation of dissolution hardware, in
      particular the United States Pharmacopeia (USP) apparatus 4 flow-through cell,
      allows measurements under controlled conditions for comparison against other
      dissolution methods. Furthermore, simultaneous image acquisition and measurement
      of drug concentration allow direct comparison of the drug release throughout the
      hydration process. The combination of low-field MRI with USP-4 apparatus provides
      another tool to aid tablet formulation.

PMID- 19602437
TI  - Alteration of the glycosylation pattern of monocytic THP-1 cells upon
      differentiation and its impact on lectin-mediated drug delivery.
AB  - In the present study, human monocytic THP-1 cells were treated with phorbol-12
      myristate-13-acetate (PMA) in order to obtain macrophage-like cells. Before and
      after treatment, plant lectins with distinct sugar specificities were applied in
      order to elucidate the glycosylation patterns of both monocytic and macrophage
      like cell types and to follow changes during differentiation. As a result of flow
      cytometric analyses, for untreated as well as for PMA-differentiated cells WGA
      yielded the highest binding rate without significant changes in the binding
      capacity. For the other lectins, divergent results were obtained which point to
      reorganization of sugar residues on the cell surface during differentiation.
      Additionally, cytoinvasion being beneficial for enhanced drug absorption was
      studied with WGA which had displayed a high binding capacity together with a high
      specificity. For both untreated and PMA-differentiated cells decreased
      fluorescence intensity at 37 degrees C as compared to 4 degrees C was observable
      pointing to internalization and accumulation within acidic compartments.
      Moreover, WGA-functionalized PLGA nanoparticles were prepared, and their uptake
      evaluated. Uptake rates of 55% in case of PMA-differentiated cells suggested that
      WGA-grafted drug delivery systems might be an interesting approach for treatment
      of infectious diseases provoked by parasites, facultative intracellular bacteria,
      or viruses such as HIV.

PMID- 19602438
TI  - Oral osmotically driven systems: 30 years of development and clinical use.
AB  - The number of marketed oral osmotically driven systems (OODS) has doubled in the
      last 10 years. The main clinical benefits of OODS are their ability to improve
      treatment tolerability and patient compliance. These advantages are mainly driven
      by the capacity to deliver drugs in a sustained manner, independent of the drug
      chemical properties, of the patient's physiological factors or concomitant food
      intake. However, access to these technologies has been restricted by the crowded
      patent landscape and manufacturing challenges. In this review article, we intend
      to give an overview of the OODS development in the last 30 years, detailing the
      technologies, specific products and their clinical use. General guidance on
      technology selection is described in light of the recent advances in the field.
      The clinical performance of these technologies is also discussed, with a focus on
      food effects and the in vivo-in vitro correlation. Special attention is paid to
      safety given the controversial case study of Osmosin. Overall, oral osmotically
      driven systems appear to be a promising technology for product life-cycle
      strategies.

PMID- 19602439
TI  - Single-step production of functional OEP24 proteoliposomes.
AB  - The pea chloroplastic outer envelope protein OEP24 is a voltage-dependent channel
      that can function as a general solute channel in plants. OEP24 is a close
      functional homologue of VDAC which, in mammalian cells, modulates the
      permeability of the outer mitochondrial membrane. Here, we describe the
      production in a one-step reaction of active OEP24 in proteoliposomes or in
      soluble form using a cell-free expression system. We combine evidence from
      electrophysiological experiments, biophysical characterization, and biochemical
      analysis demonstrating that OEP24 is present as a functional channel in
      liposomes. Thus, production of OEP-containing proteoliposomes may provide a
      helpful tool for deciphering the role of the OEP family members.

PMID- 19602440
TI  - Crystal structure of MqnD (TTHA1568), a menaquinone biosynthetic enzyme from
      Thermus thermophilus HB8.
AB  - In many microorganisms, menaquinone is an essential lipid-soluble electron
      carrier. Recently, an alternative menaquinone biosynthetic pathway was found in
      some microorganisms [Hiratsuka, T., Furihata, K., Ishikawa, J., Yamashita, H.,
      Itoh, N., Seto, H., Dairi, T., 2008. An alternative menaquinone biosynthetic
      pathway operating in microorganisms. Science 321, 1670-1673]. Here, we report the
      1.55 A crystal structure of MqnD (TTHA1568) from Thermus thermophilus HB8, an
      enzyme within the alternative menaquinone biosynthetic pathway. The structure
      comprises two domains with alpha/beta structures, a large domain and a small
      domain. L(+)-Tartaric acid was bound to the pocket between the two domains,
      suggesting that this pocket is a putative active site. The conserved glycine
      residues at positions 78, 80 and 82 seem to act as hinges, allowing the substrate
      to access the pocket. Highly conserved residues, such as Asp14, Asp38, Asn43,
      Ser57, Thr107, Ile144, His145, Glu146, Leu176 and Tyr234, are located at this
      pocket, suggesting that these residues are involved in substrate binding and/or
      catalysis, and especially, His145 could function as a catalytic base. Since
      humans and their commensal intestinal bacteria, including lactobacilli, lack the
      alternative menaquinone biosynthetic pathway, this enzyme in pathogenic species,
      such as Helicobacter pylori and Campylobacter jejuni, is an attractive target for
      the development of chemotherapeutics. This high-resolution structure may
      contribute toward the development of its inhibitors.

PMID- 19602441
TI  - Nuclear DNA assay in solving issues related to ancestry of the domesticated
      diploid safflower (Carthamus tinctorius L.) and the polyploid (Carthamus) taxa,
      and phylogenetic and genomic relationships in the genus Carthamus L.
      (Asteraceae).
AB  - The multipronged nuclear DNA assay by random amplified polymorphic DNA (RAPD)
      fingerprinting, ribosomal DNA repeat unit length polymorphism, internal
      transcribed sequence (ITS) RFLP, and comparative sequence analysis of ITS and
      external transcribed sequence (ETS) regions of the 29 accessions belonging to 18
      Carthamus taxa including five unverified species was undertaken to obtain new
      information on (1) interrelationships among botanical varieties of cultivated
      safflower, C. tinctorius, and phylogenetic relationships (2) among the safflower
      and its close relatives and (3) that of Carthamus species and subspecies. The
      root tip cells of the 12 accessions contained 24 chromosomes followed by 64, 44
      and 20 chromosomes in 9, 6 and 2 accessions, respectively. Barring C. lanatus,
      the accessions within each taxon had the same zygotic number. The present results
      strongly support the view that the wild C. palaestinus (2n=24) and the cultivated
      C. tinctorius (2n=24) are closely related. With few exceptions, all DNA based
      dendrograms support three lineages within the genus. One lineage is constituted
      by C. arborescens (2n=24) alone. The present data indicates that because of
      unique composition of its nuclear genome vis-a-vis other Carthamus taxa, C.
      arborescens should be placed in a separate subgenus. The two remaining lineages,
      constituted by the taxa with 2n=24, and the taxa with 2n=20, 2n=44 and 2n=64,
      respectively should be given the rank of two taxonomic sections in the other
      subgenus. The present study also demonstrates that none of the present taxa with
      2n=24 have contributed to the origin of polyploid taxa. Carthamus boisserii
      (2n=20) and C. glaucus ssp. anatolicus (2n=20) are more likely to be one of the
      diploid progenitor of C. lanatus ssp. creticus (2n=64), C. lanatus (2n=44), C.
      lanatus ssp. lanatus (2n=44) and C. lanatus ssp. montanus (2n=44), and C. lanatus
      ssp. turkestanicus (2n=64), respectively. Within Lanatus species complex,
      constituted by C. lanatus, C. lanatus ssp. lanatus, C. lanatus ssp. montanus, C.
      lanatus ssp. turkestanicus and C. lanatus ssp. creticus, high proportion of
      autapomorphic characters and low number of synapomorphies in the ITS and ETS
      sequences suggest a relatively recent diversification of the taxa within the
      species complex. Carthamus lanatus ssp. creticus (2n=64) and C. lanatus ssp.
      turkestanicus (2n=64) within the complex deserve species rank. This analysis
      provided evolutionary relatedness of the five unverified taxa with the known
      Carthamus taxa.

PMID- 19602442
TI  - Multilocus molecular phylogenetic analysis of the montane Craugastor podiciferus
      species complex (Anura: Craugastoridae) in Isthmian Central America.
AB  - The Craugastor podiciferus complex is a group of phenotypically polymorphic
      direct-developing frogs that inhabit the Talamancan highlands of Costa Rica and
      Panama. The montane distribution of this group creates natural allopatry among
      members and offers an excellent opportunity to explore geographic models of
      speciation. Using a multilocus approach, we obtained data from one nuclear (c
      myc) and three mitochondrial (12S, 16S, and COI) gene regions from 40 individuals
      within the C. podiciferus complex. Molecular phylogenetic analyses revealed a
      basal split that placed samples from western Panama as sister to Costa Rican (CR)
      samples, corroborating a previous suggestion that the former lineage may
      represent an undescribed species. Within the CR clades we found six distinct
      haplogroups whose distributions largely corresponded to geographic features and
      included instances of sympatry. Divergence estimates were used to develop a
      preliminary evolutionary timeframe for the diversification of the C. podiciferus
      complex. Based on collective evidence, we hypothesize that movement of the CR
      haplogroups has occurred between currently isolated areas of suitable habitat via
      second order climatic fluctuations during the Pleistocene. The levels of genetic
      differentiation within the C. podiciferus complex are remarkable given the
      relatively small geographic area (ca. 8000 km(2)) of occurrence. This diversity
      emphasizes the need for further study and taxonomic revision to aid in
      conservation planning for this complex which, like many amphibians, has
      experienced recent population declines.

PMID- 19602443
TI  - dsRNA-induced gene silencing in Moniliophthora perniciosa, the causal agent of
      witches' broom disease of cacao.
AB  - The genome sequence of the hemibiotrophic fungus Moniliophthora perniciosa
      revealed genes possibly participating in the RNAi machinery. Therefore, studies
      were performed in order to investigate the efficiency of gene silencing by dsRNA.
      We showed that the reporter gfp gene stably introduced into the fungus genome can
      be silenced by transfection of in vitro synthesized gfpdsRNA. In addition,
      successful dsRNA-induced silencing of endogenous genes coding for hydrophobins
      and a peroxiredoxin were also achieved. All genes showed a silencing efficiency
      ranging from 18% to 98% when compared to controls even 28d after dsRNA treatment,
      suggesting systemic silencing. Reduction of GFP fluorescence, peroxidase activity
      levels and survival responses to H(2)O(2) were consistent with the reduction of
      GFP and peroxidase mRNA levels, respectively. dsRNA transformation of M.
      perniciosa is shown here to efficiently promote genetic knockdown and can thus be
      used to assess gene function in this pathogen.

PMID- 19602445
TI  - Does speaker presentation affect auditory evoked potential thresholds in
      goldfish?
AB  - The auditory evoked potential (AEP) recording technique has proved to be a very
      versatile and successful approach in studying auditory sensitivities in fishes.
      The AEP protocol introduced by Kenyon, Ladich and Yan in 1998 using an air
      speaker with the fish positioned at the water surface gave auditory thresholds in
      goldfish very close to behavioural values published before. This approach was
      subsequently modified by several laboratories, raising the question whether
      speaker choice (air vs. underwater) or the position of subjects affect auditory
      threshold determination. To answer these questions, the hearing specialist
      Carassius auratus was measured using an air speaker, an underwater speaker and
      alternately positioning the fish directly at or 5cm below the water surface. Mean
      hearing thresholds obtained using these 4 different setups varied by 5.6dB, 3.7dB
      and 4dB at 200Hz, 500Hz and 1000Hz, respectively. Accordingly, pronounced
      differences in AEP thresholds in goldfish measured in different laboratories
      reflect other factors than speaker used and depth of the test subjects, namely
      variations in threshold definition, background noise, population differences, or
      calibration errors.

PMID- 19602446
TI  - Structural and autooxidation profiles of myoglobins from three species and one
      hybrid of tilapia (Cichlidae, Perciformes).
AB  - cDNAs encoding myoglobin were cloned from the slow skeletal muscles of three
      representative species of tilapia, namely, Nile tilapia Oreochromis niloticus,
      blue tilapia O. aureus, Mozambique tilapia O. mossambicus and one hybrid O.
      niloticus female symbol x O. aureus male symbol, and the primary structures were
      deduced. All cDNAs contained an open reading frame of 444 base pairs, encoding
      147 amino acids. The amino acid sequences of Mb were completely conserved among
      these species, though species variations in the nucleotide sequences were
      recognized both in coding and non-coding regions. The amino acid sequence
      identity was around 70-80% compared to other teleostean Mbs. In comparison of
      each alpha-helical segment (A through H) and the intersegment regions to the
      counterparts of tuna myoglobin, the alpha-helical segments C and F as well as the
      intersegment regions F-G and G-H were identical. The identities of alpha-helical
      segments B and H and the intersegment region F-G were relatively low. Differences
      were also recognized in the hydropathy plot and the tertiary structures obtained
      by homology modeling. The autooxidation rates at 25 degrees C of myoglobin
      fraction from the slow skeletal muscle were essentially the same among the above
      tilapia species, as expected from the conserved amino acid sequences.

PMID- 19602447
TI  - Molecular cloning and functional analysis of polymeric immunoglobulin receptor
      gene in orange-spotted grouper (Epinephelus coioides).
AB  - As one of the most important mucosal effectors, polymeric immunoglobulin receptor
      (pIgR) mediates the transcytosis of polymeric immunoglobulins (pIgs) to protect
      the organisms. In this study, a full-length cDNA of pIgR was isolated from orange
      spotted grouper (Epinephelus coioides), and the sequence analysis of deduced
      protein revealed the presence of only two Ig-like domains (ILDs), and the absence
      of the conserved Ig-binding site and complementary determining region (CDR). The
      grouper pIgR mRNA was detected in almost all the peripheral tissues examined,
      especially the mucosal tissues by RT-PCR. Additionally, recombinant grouper pIgR
      was stably expressed in the COS-7 cell line and identified as a 40-kDa
      transmembrane receptor. Furthermore, the association of recombinant pIgR and
      purified grouper pIgM was demonstrated. Taken together, the present study
      provided strong evidence that grouper pIgR was produced as a transmembrane
      protein, and probably involved in the pIgM transport.

PMID- 19602448
TI  - Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic
      review and meta-analysis.
AB  - BACKGROUND & AIMS: Small intestinal bacterial overgrowth (SIBO) has been proposed
      as an etiologic factor in irritable bowel syndrome (IBS), but evidence is
      conflicting. We conducted a systematic review and meta-analysis of the prevalence
      of SIBO in IBS. METHODS: MEDLINE and EMBASE were searched up to November 2008.
      Case series and case-control studies applying diagnostic tests for SIBO in
      unselected adults meeting diagnostic criteria for IBS were eligible. Prevalence
      of a positive test for SIBO was extracted and pooled for all studies, and
      compared between cases and controls using an odds ratio and 95% confidence
      interval (CI). RESULTS: Twelve studies were identified containing 1921 subjects
      meeting criteria for IBS. Pooled prevalence of a positive lactulose or glucose
      hydrogen breath test was 54% (95% CI, 32%-76%) and 31% (95% CI, 14%-50%),
      respectively, with statistically significant heterogeneity between study results.
      Prevalence of a positive jejunal aspirate and culture was 4% (95% CI, 2%-9%). The
      pooled odds ratio for any positive test for SIBO in cases compared with healthy
      asymptomatic controls was 3.45 (95% CI, 0.9-12.7) or 4.7 (95% CI, 1.7-12.95),
      depending on the criteria used to define a positive test, with statistically
      significant heterogeneity for both. CONCLUSIONS: Prevalence of SIBO in
      individuals meeting diagnostic criteria for IBS was highest with breath testing.
      The prevalence in cases with IBS compared with controls varied according to
      criteria used to define a positive test. The role of testing for SIBO in
      individuals with suspected IBS remains unclear.

PMID- 19602449
TI  - A community-based survey of abdominal pain prevalence, characteristics, and
      health care use among children.
AB  - BACKGROUND & AIMS: Abdominal pain is a common clinical problem among children and
      adolescents and an important public health problem. The German Health Interview
      and Examination Survey for Children and Adolescents was performed to assess
      children's health and living conditions in a representative population sample. By
      using data collected from this survey, we evaluated the prevalence and
      characteristics of abdominal pain and assessed health care use. METHODS: The
      community-based survey was carried out from May 2003 to May 2006 among children
      and adolescents living in Germany. Questionnaires were given to adolescents (age,
      11-17 y; n = 7697) and parents of children (age, 3-10 y; n = 7544). RESULTS:
      Abdominal pain causes the greatest impairment to children (32.9%). The 3-month
      prevalence rates decreased with age (39.8% in children, 41.8% [corrected] in
      adolescents; P < .001), girls reported abdominal pain significantly more often
      than boys (children: 71.5% vs 67.1%; P = .002; adolescents: 65.3% vs 53.2%; P <
      .001). Migrant adolescents were affected significantly more often by abdominal
      pain than locals (66.9% vs 58.0%; P < .001). More than half (51.6%) of the
      children and 38.5% of the adolescents visited a doctor because of abdominal pain;
      22.6% and 39.2%, respectively, used medication for abdominal pain. Pain
      characteristics were influenced by age, sex, and socioeconomic status in a
      complex fashion. CONCLUSIONS: High levels of prevalence and health care use
      reveal that abdominal pain is an important public health problem in children and
      adolescents. Abdominal pain in children is influenced by a variety of
      biopsychosocial factors.

PMID- 19602444
TI  - What is the real physiological NO concentration in vivo?
AB  - Clarity about the nitric oxide (NO) concentrations existing physiologically is
      essential for developing a quantitative understanding of NO signalling, for
      performing experiments with NO that emulate reality, and for knowing whether or
      not NO concentrations become abnormal in disease states. A decade ago, a value of
      about 1 microM seemed reasonable based on early electrode measurements and a
      provisional estimate of the potency of NO for its guanylyl cyclase-coupled
      receptors, which mediate physiological NO signal transduction. Since then,
      numerous efforts to measure NO concentrations directly using electrodes in cells
      and tissues have yielded an irreconcilably large spread of values. In
      compensation, data from several alternative approaches have now converged to
      provide a more coherent picture. These approaches include the quantitative
      analysis of NO-activated guanylyl cyclase, computer modelling based on the type,
      activity and amount of NO synthase enzyme contained in cells, the use of novel
      biosensors to monitor NO release from single endothelial cells and neurones, and
      the use of guanylyl cyclase as an endogenous NO biosensor in tissue subjected to
      a variety of challenges. All these independent lines of evidence suggest the
      physiological NO concentration range to be 100 pM (or below) up to approximately
      5 nM, orders of magnitude lower than was once thought.

PMID- 19602450
TI  - Imaging of perianal fistulas.
AB  - Perianal fistulas, cryptoglandular or Crohn's disease-related, have a tendency to
      recur. Recurrence usually is owing to missed infection during surgery for
      cryptoglandular fistulas or insufficient response to medical treatment in Crohn's
      disease. It is now recognized that preoperative imaging (endoanal ultrasound and
      magnetic resonance imaging) can help to identify extensions that otherwise would
      be missed during surgery and therefore prevent recurrence. For medical therapy,
      the extent of the disease and the presence of abscesses are identified with
      imaging and therapy response can be monitored. The purpose of this review is to
      give an up-to-date overview of the anal anatomy, classification of perianal
      fistulas, and the role of imaging modalities in the management of patients with
      perianal fistulas.

PMID- 19602451
TI  - Endoscopic resection of an ileal inflammatory fibroid polyp using retrograde
      single-balloon enteroscopy.

PMID- 19602452
TI  - Aerophagia: excessive air swallowing demonstrated by esophageal impedance
      monitoring.
AB  - BACKGROUND & AIMS: Patients with aerophagia suffer from the presence of an
      excessive volume of intestinal gas, which is thought to result from excessive air
      ingestion. However, this has not been shown thus far. The aim of this study was
      therefore to assess swallowing and air swallowing frequencies in patients with
      suspected aerophagia. METHODS: Ambulatory 24-hour pH-impedance monitoring was
      performed in patients in whom excessive amounts of intestinal gas were visualized
      on plain abdominal radiograms. All patients had symptoms of bloating, abdominal
      distention, flatulence, or excessive belching. Reflux parameters and the number
      of swallows and air swallows were assessed. RESULTS: The most common symptoms
      were bloating, abdominal distention, and constipation. Only 3 patients reported
      excessive belching and 1 patient reported flatulence as their predominant
      symptom. During the 24-hour measurement, patients showed high incidences of air
      swallows (521 +/- 63) and gastric belches (126 +/- 37). Patients had normal
      swallowing frequency (741 +/- 71). CONCLUSIONS: This study presents objective
      parameters that confirm the existence of excessive air swallowing or aerophagia
      using esophageal impedance monitoring.

PMID- 19602453
TI  - Complications associated with double balloon enteroscopy at nine US centers.
AB  - BACKGROUND & AIMS: Double balloon enteroscopy (DBE) was introduced into the US in
      2004. Potential complications include perforation, pancreatitis, and
      gastrointestinal bleeding. Prevalence and risk factors for complications have not
      been described in a US population. METHODS: We conducted a retrospective study of
      DBE complications in 9 US centers. We obtained detailed information for each
      complication including patient history, maneuvers performed during the DBE, and
      presence of altered surgical anatomy. RESULTS: We collected data from 2478 DBE
      examinations performed from 2004 to 2008. The dataset included 1691 (68%)
      anterograde DBE, 722 (29%) retrograde DBE (including 5 per-stomal DBEs), and 65
      (3%) DBE-facilitated endoscopic retrograde cholangiopancreatography ERCP cases.
      There were a total of 22 (0.9%) major complications including perforation in 11
      (0.4%), pancreatitis in 6 (0.2%), and bleeding in 4 (0.2%) patients. One of 6
      cases of pancreatitis occurred post retrograde DBE. Perforations occurred in
      3/1691 (0.2%) anterograde examinations and 8/719 (1.1%) retrograde DBEs (P =
      .004). Eight (73%) perforations occurred during diagnostic DBE examinations. Four
      of 8 retrograde DBE perforations occurred in patients with prior ileoanal or
      ileocolonic anastomoses. In the subset of 219 examinations performed in patients
      with surgically altered anatomy, perforations occurred in 7 (3%), including 1/159
      (0.6%) anterograde DBE examinations, 6/60 (10%) retrograde DBEs, and 1 of 5 (20%)
      peristomal DBE examinations (P < .005 compared with patients without surgically
      altered anatomy). CONCLUSIONS: DBE is associated with a higher complication rate
      compared with standard endoscopic procedures. The perforation rate was
      significantly elevated in patients with altered surgical anatomy undergoing
      diagnostic retrograde DBE examinations.

PMID- 19602455
TI  - Secondary tumours in Sjogren's syndrome.
AB  - The frequent association of Sjogren's syndrome (SS) with non-Hodgkin's B cell
      lymphoma (NHL) provides an example of the interplay of systemic autoimmunity and
      lymphoproliferative diseases, and an opportunity to study the pathogenetic steps
      of lymphomagenesis. NHL develops in approximately 5% of SS patients.
      Parotidomegaly, lymphadenopathy, inflammatory neuropathy and vasculitis have been
      found to be predictive of the development of lymphoma. A subsequent NHL is also
      heralded by the appearance of cryoglobulinaemia and serum or urinary monoclonal
      proteins. The typical histological type of NHL in SS is a low-grade extranodal
      marginal zone B cell lymphoma. The authors discuss the proposed key
      immunopathologic steps of lymphomagenesis in SS in detail. Recent results
      indicating the pathogenetic role of ectopic germinal centre formation in the
      involved exocrine glands, the potential importance of an antigen-driven clonal
      proliferation of autoreactive B-lymphocytes, the proposed role of the B
      lymphocyte activating factor (BAFF) and of further cytokines and, finally, the
      changes of the chemokine milieu at the site of lymphoma development are
      highlighted.

PMID- 19602454
TI  - Efficacy of radiofrequency ablation combined with endoscopic resection for
      barrett's esophagus with early neoplasia.
AB  - BACKGROUND & AIMS: Radiofrequency ablation (RFA) is safe and effective for
      eradicating intestinal metaplasia and neoplasia in patients with Barrett's
      esophagus. We sought to assess the safety and efficacy of RFA in conjunction with
      baseline endoscopic resection for high-grade intraepithelial neoplasia (HGIN) and
      early cancer. METHODS: This multicenter, prospective cohort study included 24
      patients (mean age, 65 years; median Barrett's esophagus, 8 cm), with Barrett's
      esophagus of < or =12 cm containing HGIN or early cancer, from 3 European
      tertiary-care medical centers. Visible lesions were endoscopically resected,
      followed by serial RFA. Focal escape endoscopic resection was used if Barrett
      tissue persisted despite RFA. Complete response, defined as all biopsies negative
      for intestinal metaplasia and neoplasia, was assessed during endoscopy with 4
      quadrant biopsies taken every 1 cm of the original Barrett's segment 2 months
      after the patient was last treated. RESULTS: Twenty-three patients underwent pre
      RFA endoscopic resection for visible lesions; 16 patients had early cancer and 7
      patients had HGIN. The worst residual histology results, pre-RFA (after any
      endoscopic resection) were: HGIN (10 patients), low-grade intraepithelial
      neoplasia (11 patients), and intestinal metaplasia (3 patients). Neoplasia and
      intestinal metaplasia were eradicated in 95% and 88% of patients, respectively;
      after escape endoscopic resection in 2 patients, rates improved to 100% and 96%,
      respectively. Complications after RFA included melena (n = 1) and dysphagia (n =
      1). After additional follow-up (median, 22 months; interquartile range, 17.2-23.8
      months) no neoplasia recurred. CONCLUSIONS: This European multicenter study to
      show that early neoplasia in Barrett's esophagus can be effectively and safely
      treated with RFA, in combination with prior endoscopic resection of visible
      lesions.

PMID- 19602456
TI  - Methods used to assess remission and low disease activity in rheumatoid
      arthritis.
AB  - The aim of the treatment in rheumatoid arthritis (RA) is to prevent articular
      damage and functional loss by decreasing the activity of the disease. The overall
      goal is the full suppression of the activity of the disease, also called clinical
      remission. The most reliable indices to assess RA activity were defined by the
      American College of Rheumatology (ACR), the European League Against Rheumatism
      (EULAR) and the International League Against Rheumatism (ILAR) and are habitually
      used for the evaluation of remission. The Food and Drug Administration (FDA)
      established three increasingly restrictive categories of disease remission:
      complete clinical response, major clinical response, and remission. Then, OMERACT
      (Outcome Measures in Rheumatoid Arthritis Clinical Trials) advanced the concept
      of low disease activity state (LDAS) or minimal disease activity (MDA). Thus,
      those reported by FDA are the only criteria for remission which consider
      radiographic arrest of the disease. This review aims to describe the criteria for
      RA remission and to discuss their advantages and limitations.

PMID- 19602457
TI  - A comparison of the effects of prosthetic and commercially pure metals on
      retrieved human fibroblasts: the role of surface elemental composition.
AB  - The most common clinical cause of long-term failure in total joint replacement
      surgery is inflammatory aseptic osteolysis; a condition in which bone surrounding
      the prosthetic implant, and to which the implant is attached, is resorbed,
      rendering the artificial device loose and painful. Historically, the severity of
      this bone resorptive process has been thought to be predominately attributed to
      the size and shape of wear-debris particles, particularly the metallic
      particulates that interact biologically/immunologically with cells in the joint.
      Because the cytotoxic reactions are the result of interactions between the cells
      and the surfaces of the particulates, it is not clear in the realm of orthopedics
      to what extent different surface stoichiometric ratios contribute to instigating
      bioreactive or cytotoxic cellular responses that can lead to aseptic osteolysis.
      Using energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron
      spectroscopy (XPS), this study presents data and analyses concerning the
      respective bulk and surface stoichiometric ratios of two commercially pure metal
      micro-particulates (tantalum and titanium), two prosthetic F75 cobalt-chromium
      molybdenum alloy micro-particulates, and prosthetic F136 titanium-aluminum
      vanadium alloy micro-particulates, each containing elements common to total joint
      replacement surgery. Cell culture viability data from four volunteer donors are
      also presented, which suggest that micro-particulates containing large
      percentages of surface titanium and aluminum can cause moderate cellular
      toxicity, and micro-particulates containing large percentages of surface cobalt
      can result in extremely severe cellular toxicity. This work further suggests that
      surface analysis techniques, such as XPS, are essential to determine surface
      elemental characterization of metallic materials prior to interpreting cellular
      response results.

PMID- 19602458
TI  - Molecular and immunohistochemical analyses of BCL2, KI-67, and cyclin D1
      expression in synovial sarcoma.
AB  - Synovial sarcoma (SS) is a highly aggressive soft tissue sarcoma that causes
      death in more than half of the affected patients. An immunohistochemical and
      molecular study of the BCL2, MKI67, and CCND1 genes (expressing the BCL2, KI-67,
      and cyclin D1 proteins, respectively) was performed to determine the expression
      profiles in correlation with mRNA levels, and to assess the possible utility of
      these genes as a potential target for the treatment. Cyclin D1 staining was
      identified in 18 of 30 cases (60%), and CCND1 mRNA was overexpressed in 15 of 32
      cases (47%). KI-67 nuclear immunoreactivity was found in 14 of 29 cases (48%),
      and MKI67 mRNA was overexpressed in 12 of 32 cases (37.5%). The high level of
      MKI67 mRNA was observed predominantly in monophasic SS. BCL2, a negative
      regulator of apoptosis, was expressed in all 32 cases. The intensity of the BCL2
      protein expression correlated well with the mRNA level (P<0.0001). The high level
      of BCL2 mRNA correlated with a high level of CCND1 mRNA, but not with MKI67 mRNA
      level. Despite advances in therapy of sarcomas, the prognosis of patients with SS
      remains unfavorable, and a search for an improved therapy approach remains
      necessary. The strong immunopositivity of BCL2 in SS correlates well with a high
      level of BCL2 mRNA. Treatment with antisense BCL2 (G3139) may therefore represent
      an appropriate alternative therapy for patients with BCL2-positive synovial
      sarcomas.

PMID- 19602459
TI  - Molecular inversion probes reveal patterns of 9p21 deletion and copy number
      aberrations in childhood leukemia.
AB  - Childhood leukemia, which accounts for >30% of newly diagnosed childhood
      malignancies, is one of the leading causes of death for children with cancer.
      Genome-wide studies using microarray chips to identify copy number changes in
      human cancer are becoming more common. In this pilot study, 45 pediatric leukemia
      samples were analyzed for gene copy aberrations using novel molecular inversion
      probe (MIP) technology. Acute leukemia subtypes included precursor B-cell acute
      lymphoblastic leukemia (ALL) (n=23), precursor T-cell ALL (n=6), and acute
      myeloid leukemia (n=14). The MIP analysis identified 69 regions of recurring copy
      number changes, of which 41 have not been identified with other DNA microarray
      platforms. Copy number gains and losses were validated in 98% of clinical
      karyotypes and 100% of fluorescence in situ hybridization studies available. We
      report unique patterns of copy number loss in samples with 9p21.3 (CDKN2A)
      deletion in the precursor B-cell ALL patients, compared with the precursor T-cell
      ALL patients. MIPs represent an attractive technology for identifying novel copy
      number aberrations, validating previously reported copy number changes, and
      translating molecular findings into clinically relevant targets for further
      investigation.

PMID- 19602460
TI  - Chromosomal copy number changes of locally advanced rectal cancers treated with
      preoperative chemoradiotherapy.
AB  - Standard treatment of rectal cancer patients comprises preoperative
      chemoradiotherapy followed by radical surgery. However, clinicians are faced with
      the problem that response rates vary from one individual to another. Predictive
      biomarkers would therefore be helpful. To identify genomic imbalances that might
      assist in stratifying tumors into responsive or nonresponsive categories, we used
      metaphase comparative genomic hybridization to prospectively analyze
      pretherapeutic biopsies from 42 patients with locally advanced rectal cancers.
      These patients were subsequently treated with 5-fluorouracil-based preoperative
      chemoradiotherapy. Based on downsizing of the T-category, 21 rectal cancers were
      later classified as responsive, while the other 21 were nonresponsive. Comparing
      these two groups, we could show that gains of chromosomal regions 7q32
      approximately q36 and 7q11 approximately q31, as well as amplifications of 20q11
      approximately q13, were significantly associated with responsiveness to
      preoperative chemoradiotherapy (P<0.05). However, the probability of detecting
      these copy number changes by chance is high (P=0.21). Our primary results suggest
      that pretherapeutic evaluation of chromosomal copy number changes may be of value
      for response prediction of rectal cancers to preoperative chemoradiotherapy. This
      will require validation in a larger cohort of patients.

PMID- 19602461
TI  - Chromosomal changes in aggressive breast cancers with basal-like features.
AB  - Using high-resolution oligonucleotide comparative genomic hybridization arrays,
      we evaluated chromosomal copy number changes in a series of 16 breast cancers,
      selected on the basis of highly similar pathologic and molecular features
      characteristic of the "basal-like" phenotype. Each of these cancers showed
      numerous gains and losses, reflecting multiple chromosomal rearrangements during
      the development of these high-grade cancers. Chromosomal losses were particularly
      prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were
      commonly seen on chromosomal arms 1q, 8q, and 17q. The regions of high-level
      amplification (copy number change more than eightfold) on 4q12, 8q23.3, 19p12,
      and 19q13.2 were particularly remarkable. These regions included candidate
      oncogenes cKIT, JUND, and AKT2, and immunohistochemistry confirmed that these
      particular genes were highly expressed in the cancers harboring the specific
      amplifications. Each of these amplifications was observed only in individual
      cases, however, and no particular chromosomal alteration appeared to generally
      characterize this group of cancers. Thus, genomic changes among breast cancers
      with basal-like features appear to be very heterogeneous. Distinct high-level
      amplifications may provide new targets for treating some of these cancers, but
      copy number changes do not reveal a distinctive genomic fingerprint for this
      proposed class of breast cancers.

PMID- 19602462
TI  - Cytogenetic effects of recombinant interferon-gamma on lymphocytes cultures from
      patients with non-small cell lung cancer.
AB  - Therapeutic effects of human interferons (IFN) on malignancies and infectious
      diseases have been demonstrated in several clinical trials. The effects of IFN
      alone or combined with other treatment modalities (radiotherapy and chemotherapy)
      in lung cancer are under investigation. Experimental data suggest that some
      cytokines, such as IFN-alpha and IFN-gamma, exhibit cytogenetic properties in
      human normal lymphocytes from peripheral blood, but the mechanisms are not clear.
      The aim of the present study was to investigate the in vivo cytotoxic and
      cytostatic activity of IFN-gamma. Patients with certain cases of non-small cell
      lung cancer not eligible for chemotherapy or chemoradiotherapy were treated with
      thoracic radiotherapy. After tumor relapse, local treatment with instillations of
      IFN-gamma through the fiberoptic bronchoscope followed. To clarify the
      cytogenetic activity of IFN-gamma, sister chromatid exchange (SCE) and
      proliferation rate index (PRI) were evaluated in lymphocyte cultures from these
      patients' peripheral blood samples immediately after diagnosis (baseline), 30
      days after radiotherapy, and after the fifth instillation of IFN-gamma. Our
      results show a decrease in SCE frequency and PRI values in lymphocytes after
      treatment with IFN-gamma, suggesting that IFN-gamma does not have cytotoxic
      activity but, in contrast, may induce repair mechanisms, as shown in earlier
      studies in other biologic models.

PMID- 19602463
TI  - Gene amplification in myeloid leukemias elucidated by fluorescence in situ
      hybridization.
AB  - Gene amplification in hematologic malignancies is uncommon. When karyotyping
      leukemia cells, gene amplification is generally seen as double-minute (dmin)
      chromosomes and homogeneously staining regions (hsr). One of the more commonly
      amplified regions is MYC at 8q24.21, but amplification of MLL at 11q23 and
      regions on 9p, 19q, and elsewhere on 11q have been reported. Increased copy
      number of these genes has been associated with poor prognosis. Over an 11-year
      period, we identified 31 cases of possible gene amplification, 27 of which had
      enough sample material for further investigations. A total of 17 cases had dmin
      only, 13 cases had hsr only, and 1 case had both dmin and hsr in the karyotype.
      Fluorescence in situ hybridization (FISH) analysis identified amplification of
      MYC in 12 cases, all on dmin, and amplification of MLL in eight cases, all on
      hsr. Regions other than MYC and MLL were amplified in eight cases and, using
      multicolor FISH and multicolor banding, we identified a number of novel regions
      of amplification: 13q11 approximately q12.1, 15q26.1 approximately q26.3, and
      17q12. We also identified one case where two different chromosomal regions were
      simultaneously amplified in the same cell line.

PMID- 19602464
TI  - Characterization of a recurrent t(1;2)(p36;p24) in human uterine leiomyoma.
AB  - Uterine leiomyomas are the most common neoplasms in women of reproductive age.
      Approximately 40% of these neoplasms show recurring structural cytogenetic
      anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and
      anomalies affecting 6p21 or 10q22. Using positional cloning strategies, we and
      others had previously identified HMGA1, HMGA2, RAD51L1, and MYST4 (previously
      referred to as MORF); as primary target (fusion) genes associated with tumor
      development in three of these distinct cytogenetic subgroups. Here, we report the
      positional cloning of a single, recurrent, leiomyoma-associated anomaly,
      t(1;2)(p36;p24). Molecular characterization of the reciprocal breakpoint
      intervals showed that that AJAP1 (alias SHREW1) and NPHP4 flank the breakpoint on
      chromosome 1 and that ITSN2 and NCOA1 flank the breakpoint on chromosome 2.
      Detailed analysis of the breakpoint regions revealed that in this particular case
      the translocation was associated with a 27-bp deletion on chromosome 1 and a 136
      bp duplication on chromosome 2. No breakpoint-spanning (fusion) genes were
      identified. In silico prediction of transcription factor binding sites, however,
      indicated the presence of several such sites in the respective breakpoint
      regions, and major changes therein as a result of the t(1;2)(p36;p24) under
      investigation. We postulate that transcriptional deregulation of one or more of
      these breakpoint-flanking genes may contribute to the development of human
      uterine leiomyomas.

PMID- 19602465
TI  - The TP53 gene promoter is not methylated in families suggestive of Li-Fraumeni
      syndrome with no germline TP53 mutations.
AB  - Germline TP53 mutations are found in only 70% of families with the Li-Fraumeni
      syndrome (LFS), and with an even lower frequency in families suggestive of LFS
      but not meeting clinical criteria of the syndrome. Despite intense efforts, to
      date, no other genes have been associated with the disorder in a significant
      number of TP53 mutation-negative families. A search for defects in TP53 other
      than heterozygous missense mutations showed that neither intron variants nor
      sequence variants in the TP53 promoter are frequent in LFS, and multiexon
      deletions have been found to be responsible for LFS only in several cases.
      Another cancer predisposition syndrome, hereditary non-polyposis colon cancer,
      has been associated with epigenetic silencing of one allele of the MLH1 or MSH2
      genes. This prompted us to test the methylation of the TP53 gene promoter in a
      set of 14 families suggestive of LFS using bisulphite sequencing of three DNA
      fragments from the 5' region of the gene. We found no detectable methylation at
      any of the CG dinucleotides tested. Thus, epigenetic silencing of the TP53
      promoter is not a frequent cause of the disorder in families suggestive of LFS
      but with no germline mutations in the coding part of the gene.

PMID- 19602466
TI  - Acute myeloid leukemia (M2) with a cryptic RUNX1/RUNX1T1 t(1;21;8)(p36;q22;q22)
      variant.

PMID- 19602467
TI  - Biopsy of renal masses: when and why.
AB  - Percutaneous image-guided biopsy of renal masses is a safe and accurate
      procedure. Although once reserved for the diagnosis of unresectable renal cell
      carcinoma, metastases, lymphoma, and infection, today percutaneous image-guided
      biopsy has an expanded role. There is increasing awareness that a substantial
      proportion of small, solid renal masses are benign neoplasms. Although imaging
      can be used to diagnose most of them, some are incorrectly believed to represent
      renal cell carcinoma and unnecessary surgery may be performed. Based largely on
      advances in cytological techniques, percutaneous biopsy can be now be used to
      diagnose benign neoplasms and thus prevent them from being treated unnecessarily.
      Concurrent advances in percutaneous ablation have also promoted its use. As a
      result, there are 8 established indications for percutaneous biopsy, and reason
      to believe that the number of indications will expand further in the future.

PMID- 19602468
TI  - Endodermal sinus tumor: a rare cause of calcified peritoneal implants.
AB  - Calcified peritoneal implants have been attributed to various malignant and
      benign causes. We present an interesting case of a 32-year-old woman who
      presented with abdominal pain, distension and vaginal bleeding. Contrast-enhanced
      computed tomography revealed calcified peritoneal implants with a malignant
      ovarian mass. Histopathology showed an endodermal sinus tumor, a rare cause of
      calcified peritoneal carcinomatosis.

PMID- 19602469
TI  - Hemangiopericytoma: an unusual cause of peritoneal carcinomatosis.
AB  - Hemangiopericytoma, a rare mesenchymal tumour, is believed to originate from the
      pericyte of Zimmermann. It may affect every organ in the body. Recurrences after
      treatment and metastasis are well known. However, presentation of
      hemangiopericytoma with peritoneal carcinomatosis is not documented in
      literature. To the best our knowledge, we report the imaging findings of the
      first histologically proven case of hemangiopericytoma with peritoneal
      carcinomatosis.

PMID- 19602471
TI  - Risk of suicide among operated and non-operated patients hospitalised for peptic
      ulcers.
AB  - BACKGROUND: Some small studies have reported high risk of suicide after surgical
      treatment for peptic ulcer. The aim of the present study was to explore the risk
      of suicide in hospitalised gastric ulcer and duodenal ulcer patients separately
      among operated and non-operated cohorts. METHODS: Retrospective cohorts of
      163,579 non-operated patients with gastric ulcer or duodenal ulcer and 28,112
      patients with surgical treatment for ulcer, recorded in the Swedish Inpatient
      Register since 1965, were followed from the first hospitalisation, or operation
      for the surgery cohort, until death, any cancer, emigration, or 31 December 2003.
      Standardised mortality ratios (SMRs) were calculated, and Poisson regression
      produced adjusted relative risk estimates among operated and non-operated
      patients. RESULTS: Non-operated patients hospitalised for peptic ulcer showed a
      70% excess risk of suicide (SMR 1.7, 95% CI 1.6 to 1.9) and those who underwent
      operation had a 60% increased risk (SMR 1.6, 95% CI 1.4 to 1.8). The risk of
      suicide was very high during the first year after hospitalisation (SMR 4.0, 95%
      CI 3.4 to 4.7) and more marked among women, patients under 70 and patients
      hospitalised without complications of ulcer. Both gastric ulcer and duodenal
      ulcer patients had high risk of suicide completion. CONCLUSION: Hospitalised
      patients with gastric ulcer or duodenal ulcer have an increased risk of suicide
      regardless of surgical treatment. These patients, especially women, are at very
      high risk during the first year after first hospitalisation/operation. The
      evaluation and management of suicidal thoughts in patients in medical settings
      should be further considered.

PMID- 19602470
TI  - PET-CT imaging in pediatric oncology.
AB  - Positron emission tomography (PET)-computed tomography (CT) is emerging as a
      valuable tool for assessing a wide variety of pediatric malignancies, including
      lymphomas, soft-tissue tumors, and bone sarcomas. PET-CT may provide information
      that is not apparent on conventional imaging performed to stage these diseases
      and monitor their response to treatment. The use of PET-CT in children requires
      an awareness of the technical and logistical issues unique to this patient
      population. In addition, interpretation of pediatric PET-CT imaging requires
      familiarity with aspects of pediatric anatomy and physiology that differ from
      those of adults. In this article, the technical considerations in performing
      pediatric PET-CT, pitfalls in the diagnostic use of PET-CT in children, and
      current and emerging applications of PET-CT in pediatric oncology are reviewed.

PMID- 19602473
TI  - S-100B and neuron specific enolase are poor outcome predictors in severe
      traumatic brain injury treated by an intracranial pressure targeted therapy.
AB  - OBJECTIVE: To prospectively study S-100B and neuron specific enolase (NSE) levels
      in subjects treated for severe head injury (sTBI), and investigate the prognostic
      value of these biomarkers. METHODS: Subjects included in a prospective double
      blind randomised study for sTBI. INCLUSION CRITERIA: Glasgow Coma Score (GCS)
      <or=8, age 15-70 years, first recorded cerebral perfusion pressure of >10 mm Hg
      and arrival <24 h after trauma. Subjects were treated with an intracranial
      pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn
      immediately after arrival and every 12 h for 5 days. Outcome was evaluated as
      Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. RESULTS: 48
      subjects, mean age 35.5 years, and median GCS 6 were included. The first blood
      sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B
      was 1.04 (0.21) microg/l and for NSE 18.94 (2.32) microg/l. The biomarkers were
      significantly higher in subjects with GCS 3 and in those who died compared with
      those with GCS 4-8 and GOS 2-5, respectively. Receiver operated characteristic
      curve analyses of the initial S-100B and NSE levels to GOS dichotomised as
      unfavourable (GOS 1-3) and favourable (GOS 4-5) showed a weak correlation: AUC
      0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS
      2-5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a
      correlation was found between the biomarkers themselves and the biomarkers and
      ICP. CONCLUSION: At 3 and 12 months after trauma, no differences in prognostic
      values between the markers were apparent nor was there any clinical significant
      value of the markers as predictors of clinical outcome.

PMID- 19602474
TI  - Prestroke physical activity and early functional status after stroke.
AB  - BACKGROUND: The importance of physical activity as a modifiable risk factor for
      stroke in particular and cardiovascular disease in general is well documented.
      The effect of exercise on stroke severity and stroke outcomes is less clear. This
      study aimed to assess that effect. METHODS: Data collected for patients enrolled
      in the Ischemic Stroke Genetics Study were reviewed for prestroke self-reported
      levels of activity and four measures of stroke outcome assessed at enrollment and
      approximately 3 months after enrollment. Logistic regression was used to assess
      the association between physical activity and stroke outcomes, unadjusted and
      adjusted for patient characteristics. RESULTS: A total of 673 patients were
      enrolled; 50.5% reported aerobic physical activity less than once a week, 28.5%
      reported aerobic physical activity one to three times weekly, and 21% reported
      aerobic physical activity four times a week or more. Patients with moderate and
      high levels of physical activity were more likely to have higher Barthel Index
      (BI) scores at enrollment. A similar association was detected for exercise and
      good outcomes for the Oxford Handicap Scale (OHS). After 3 months of follow-up,
      moderate activity was still associated with a high BI score. No significant
      association was detected for activity and the OHS or Glasgow Outcome Scale at
      follow-up after adjustment for patient characteristics. CONCLUSIONS: Higher
      levels of self-reported prestroke physical activity may be associated with
      functional advantages after stroke. Our findings should be seen as exploratory,
      requiring confirmation, ideally in a longitudinal study of exercise in an older
      population.

PMID- 19602472
TI  - Lipid and endothelium-related genes, ambient particulate matter, and heart rate
      variability--the VA Normative Aging Study.
AB  - BACKGROUND: Many studies have shown that exposures to air pollution are
      associated with cardiovascular events, although the mechanism remains to be
      clarified. To identify whether exposures to ambient particles act on autonomic
      function via the lipid/endothelial metabolism pathway, whether effects of
      particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate
      variability (HRV) were modified by gene polymorphisms related to those pathways
      were evaluated. METHODS: HRV and gene data from the Normative Aging Study and
      PM(2.5) from a monitor located a kilometre from the examination site were used. A
      mixed model was fitted to investigate the associations between PM(2.5) and
      repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE),
      lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting
      for potential confounders chosen a priori. RESULTS: A 10 microg/m(3) increase in
      PM(2.5) in the 2 days before the examination was associated with 3.8% (95% CI
      0.2% to 7.4%), 7.8% (95 CI 0.4% to 15.3%) and 10.6% (95% CI 1.8% to 19.4%)
      decreases of the standard deviation of normal-to-normal intervals, the low
      frequency and the high frequency, respectively. Overall, carriers of wild-type
      APOE, LPL and VEGF genes had stronger effects of particles on HRV than those with
      hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C
      significantly modified effects of PM(2.5) on HRV. CONCLUSION: Associations
      between PM(2.5) and HRV were modified by gene polymorphisms of APOE, LPL and
      VEGF; the biological metabolism remains to be identified.

PMID- 19602475
TI  - B-cell-attracting chemokine CXCL13 as a marker of disease activity and renal
      involvement in systemic lupus erythematosus (SLE).
AB  - OBJECTIVES: The chemokine CXCL13, also known as BCA-1 (B-cell-attracting
      chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B
      cell trafficking. We have recently shown that excessive expression of dendritic
      cell-derived CXCL13 is a distinctive early event for nephritis in a murine model
      of systemic lupus erythematosus (SLE). Furthermore, in kidney biopsies from SLE
      patients, CXCL13 protein and mRNA are strongly expressed in B-cell-containing
      inflammatory lesions. Here, we ask whether serum levels of CXCL13 correlate with
      disease activity and renal involvement in SLE patients. METHODS: CXCL13 was
      measured in sera obtained from 91 patients with SLE and 40 healthy controls by
      ELISA methodology. Disease activity was calculated according to the SLE Disease
      Activity Index (SLEDAI). RESULTS: Median (IQR) serum CXCL13 concentrations were
      increasingly higher across the following groups: healthy controls [31.6 (26.8
      41.3) pg/ml], SLE patients with inactive disease (SLEDAI <6) [68.2 (27.8-133.0)
      pg/ml, P = 0.0006 versus controls] and active disease [196.0 (75.9-416.8) pg/ml,
      P = 0.0001 versus controls] (inactive versus active P < 0.0001). Concentrations
      of circulating CXCL13 correlated with SLEDAI (r = 0.56, P < 0.0001) and double
      stranded DNA titres (r = 0.36, P < 0.0005). Moreover, median CXCL13
      concentrations were higher in patients with renal involvement [175.5 (105.3
      422.6) pg/ml] compared to those without renal involvement [82.1 (42.9-219.8)
      pg/ml]. CONCLUSIONS: Our data indicate that increased level of CXCL13 is a
      feature of SLE that correlates with disease activity. Furthermore, CXCL13 might
      be a readily available surrogate marker to monitor the extent of aberrant B-cell
      (dys-)function.

PMID- 19602476
TI  - Renal transplantation in systemic vasculitis: when is it safe?
AB  - BACKGROUND: There are no clear guidelines on renal transplantation in patients
      with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. METHODS: We
      undertook a survey of transplant centres across Europe to assess whether there
      was consensus about how to manage transplantation in patients with vasculitis. We
      then identified 107 renal allograft recipients whose primary disease was systemic
      vasculitis and assessed their outcome post-transplant. RESULTS: All questionnaire
      respondents felt that vasculitis should be in remission at transplantation, 16%
      believed that ANCA should be negative pre-transplant and 40% felt that one should
      wait >12 months after remission before transplanting. Remission was defined by
      all as an absence of clinical symptoms of vasculitis, but three respondents (13%)
      also required a negative ANCA test. Overall graft survival was 70% after 10 years
      (95% C.I. 58-82). A total of 30 (41% of those with known ANCA status) were ANCA
      positive peri-transplantation, while 15 (14%) were transplanted <1 year post
      remission. Severe vasculopathy occurred more frequently in ANCA-positive
      recipients (odds ratio 4.4, 95% C.I. 1.1-16.8, P < 0.05), although causation
      cannot be determined from this study. Vasculopathy significantly reduced 10-year
      graft survival to 47% (P < 0.05). However, ANCA status per se was not
      significantly associated with graft failure. The strongest predictor of death was
      transplantation <1 year post-vasculitis remission on both univariate and
      multivariate analysis (hazard ratio 2.3, P < 0.05). CONCLUSIONS: In conclusion,
      circulating ANCA at transplant was associated with the development of vascular
      lesions in the graft but was not significantly correlated with graft survival.
      Most grafts were lost due to patient death, which was more likely if
      transplantation occurred <12 months following induction of remission of ANCA
      positive vasculitis.

PMID- 19602477
TI  - Comment on: Investigation of candidate polymorphisms and disease activity in
      rheumatoid arthritis patients on methotrexate.

PMID- 19602478
TI  - Early rheumatoid arthritis and body composition.
AB  - OBJECTIVES: RA is associated with joint destruction and cardiovascular diseases
      (CVDs). Possible predictors for CVD are early changes in body composition. We
      therefore evaluated whether lean mass of arms and legs (LMAL), total body fat
      mass (BFM) or truncal fat distribution (TFD) are altered early in RA, and if so,
      which factors are associated. METHODS: We included 132 RA patients (95 women)
      with disease duration of < or =12 months. Disease activity score (DAS28), HAQ,
      BMI, comorbidity, smoking and medications were recorded. Total and regional lean
      mass and fat mass were measured with DXA. Data were compared with 132 age- and
      gender-matched controls, and possibly associated factors were analysed in linear
      regression models. RESULTS: LMAL was low in patients for both women and men (P =
      0.007 and <0.001, respectively). BMI (P = 0.012), BFM (P = 0.014) and TFD (P <
      0.001) were higher than expected in RA women. In bivariate analyses, all adjusted
      for age and current smoking, disease duration was independently associated with
      low LMAL in women (P = 0.021). High BFM was associated with HAQ x disease
      duration in men (P = 0.033) and DAS28 in women (P = 0.011). High TFD was
      associated with a history of diabetes or CVD in men with RA (P = 0.005).
      CONCLUSIONS: Low LMAL, high BFM and high TFD are present in early RA patients.
      The long-term significant consequences of these abnormalities need to be
      determined.

PMID- 19602479
TI  - Why aren't we all doing ultrasound?

PMID- 19602481
TI  - Analysis of Dp71 contribution in the severity of mental retardation through
      comparison of Duchenne and Becker patients differing by mutation consequences on
      Dp71 expression.
AB  - The presence of variable degrees of cognitive impairment, extending from severe
      mental retardation to specific deficits, in patients with dystrophinopathies is a
      well-recognized problem. However, molecular basis underlying mental retardation
      and its severity remain poorly understood and still a matter of debate. Here, we
      report one of the largest study based on the comparison of clinical, cognitive,
      molecular and expression data in a large cohort of 81 patients affected with
      Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) bearing
      mutations predicted to affect either all dystrophin products, including Dp71 or
      all dystrophin products, except Dp71. In addition to the consistent data defining
      molecular basis underlying mental retardation in DMD, we show that BMD patients
      with MR have mutations that significantly affect Dp71 expression or with
      mutations located in exons 75 and 76. We also show that mutations upstream to
      exon 62, with DMD phenotype, predicted to lead to a loss-of-function of all
      dystrophin products, except Dp71 isoform, are associated, predominantly, with
      normal or borderline cognitive performances. Altogether, these reliable phenotype
      genotype correlations in combination with Dp71 mRNA and protein expression
      studies, strongly indicate that loss-of-function of all dystrophin products is
      systematically associated with severe form of MR, and Dp71 deficit is a factor
      that contributes in the severity of MR and may account for a shift of 2 SD
      downward of the intelligence quotient.

PMID- 19602480
TI  - Tissue-specific alternative splicing of TCF7L2.
AB  - Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been
      identified as the strongest genetic risk factors for type 2 diabetes (T2D).
      However, the mechanisms by which these non-coding variants increase risk for T2D
      are not well-established. We used 13 expression assays to survey mRNA expression
      of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human
      tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle,
      subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue
      specific pattern of alternative splicing. We tested whether the expression of
      TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs),
      rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most
      strongly associated with T2D. Expression of two splicing forms was lower in
      pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a
      ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372)
      and a splicing form found in pancreatic islets, pancreas and colon but not in
      other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146).
      Expression of this form in glucose-stimulated pancreatic islets correlated with
      expression of proinsulin (r(2) = 0.84-0.90, P < 0.00063). In summary, we
      identified a tissue-specific pattern of alternative splicing of TCF7L2. After
      adjustment for multiple tests, no association between expression of TCF7L2 in
      eight types of human tissue samples and T2D-associated genetic variants remained
      significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future
      studies. GenBank Accession Numbers: FJ010164-FJ010174.

PMID- 19602482
TI  - Antagonistic SR proteins regulate alternative splicing of tumor-related Rac1b
      downstream of the PI3-kinase and Wnt pathways.
AB  - The small GTPase Rac1 regulates signaling pathways controlling actin-dependent
      cell motility as well as gene transcription. An alternative splicing variant
      Rac1b is overexpressed in a subset of colorectal tumors and is required to
      sustain tumor cell viability. Thus, it is of therapeutic interest to understand
      the molecular mechanism behind the overexpression of Rac1b through alternative
      splicing. Here we describe that ASF/SF2 and SRp20 are two antagonistic splicing
      factors regulating Rac1b expression in colorectal tumor cells. Using an Rac1
      minigene, we identified that SRp20 increased skipping of alternative exon 3b in
      HT29 colorectal cells, whereas ASF/SF2 increased its inclusion. The depletion of
      the endogenous expression of these splicing factors by specific small interfering
      RNA confirmed that ASF/SF2 acts as an enhancer of endogenous Rac1b splicing,
      whereas SRp20 acts as a silencer. Point mutations in exon 3b defined two adjacent
      regulatory regions required for skipping or inclusion of exon 3b, which are
      recognized in vitro by SRp20 and ASF/SF2, respectively. Both splicing factors
      were found to be regulated by upstream signaling pathways: the inhibition of the
      phosphatidylinositol 3-kinase pathway increased protein levels of ASF/SF2 and
      promoted Rac1b, whereas activation of beta-catenin/TCF4 increased expression of
      SRp20 and inhibited that of Rac1b. Together, these data reveal that signaling
      pathways act in concert to target independent splicing factors and achieve the
      correct combinatorial code to regulate alternative splicing of the small GTPase
      Rac1.

PMID- 19602483
TI  - Pantothenate kinase-associated neurodegeneration: insights from a Drosophila
      model.
AB  - Pantothenate-Kinase-Associated-Neurodegeneration (PKAN) is a devastating disease,
      resulting from mutations in pantothenate kinase 2 (PANK2), one of the four human
      pantothenate kinase genes (PANK1-4). Interestingly, PanK2 appears to be the only
      mitochondria-targeted human PanK. It is unknown whether the mitochondria-targeted
      PanK is associated with any unique function, nor whether PKAN is due solely to
      the loss of pantothenate kinase activity. Drosophila PANK [fumble (fbl)] encodes
      several isoforms of pantothenate kinase products, one of which localizes to
      mitochondria and the others cytosol. fbl flies exhibit many characteristic
      features reminiscent of PKAN patients. Various forms of Drosophila fbl and human
      PANK2 were introduced into fbl flies to study their in vivo functions. Only
      mitochondria-targeted Fbl or human PanK2 was able to rescue fbl mutation, with
      the rescuing ability sensitive to the expression level of the transgene.
      Transgenic lines with low expression of normal Fbl or PanK2 displayed similar
      phenotypes as PANK2 mutant transgenic flies. These PanK2 mutants all showed
      reduced and phenotype severity-correlated in vitro pantothenate kinase
      activities. Amazingly, cytosolic PanK3 and PanK4 could mostly, but not fully,
      rescue fbl defects except the male sterility. Therefore, fbl appears to be the
      orthologue of human PANK2, and PanK2 is functionally more potent than PanK3 and
      PanK4 in vivo. We suggest that mitochondria-located pantothenate kinase is
      required to achieve the maximal enzymatic activity to fulfill the most
      challenging task such as maintaining male fertility and optimal neuronal
      functions, and PKAN features are mainly due to the reduction of the total
      cellular pantothenate kinase activity in the most susceptible regions.

PMID- 19602485
TI  - Evidence behind the WHO guidelines: hospital care for children: what is the role
      of HIV antigen testing in infants <12-months old?

PMID- 19602486
TI  - The factors that have a role in variability for temperature.
AB  - Our objective was to determine the factors that affect (i) the rectal-axillary
      temperature measurement difference (RATD) for digital and mercury-in-glass
      thermometers and (ii) the difference between mercury-in-glass and digital
      thermometer readings taken by the rectal and axillary routes. Children (between
      the ages of 2 and 48 months) who were admitted to Hacettepe University Children
      Hospital and Corum Children's Hospital in 2 months period were included in this
      study. Two measurements were taken from each patient within 2 days at two
      different occasions including day/night and sleep/awake by the same physician. A
      total of 135 patients were enrolled. RATD was 0.61 + 0.54 degrees C in the
      mercury-in-glass thermometer, and 0.81 +/- 0.57 degrees C in the digital
      thermometer. The mean differences between digital and mercury-in-glass
      thermometers were 0.16 degrees C for rectal routes and -0.02 degrees C for
      axillary routes. Children at older age with hypoalbuminemia and children exposed
      to higher ambient temperatures had lower values of RATD than others. Temperature
      recordings from different sites might change with ambient temperature and
      individual characteristics of children.

PMID- 19602484
TI  - Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in
      cellular stress responses.
AB  - Shwachman-Diamond syndrome (SDS; OMIM 260400) results from loss-of-function
      mutations in the Shwachman-Bodian Diamond syndrome (SBDS) gene. It is a multi
      system disorder with clinical features of exocrine pancreatic dysfunction,
      skeletal abnormalities, bone marrow failure and predisposition to leukemic
      transformation. Although the cellular functions of SBDS are still unclear, its
      yeast ortholog has been implicated in ribosome biogenesis. Using affinity capture
      and mass spectrometry, we have developed an SBDS-interactome and report SBDS
      binding partners with diverse molecular functions, notably components of the
      large ribosomal subunit and proteins involved in DNA metabolism. Reciprocal co
      immunoprecipitation confirmed the interaction of SBDS with the large ribosomal
      subunit protein RPL4 and with DNA-PK and RPA70, two proteins with critical roles
      in DNA repair. Function for SBDS in response to cellular stresses was implicated
      by demonstrating that SBDS-depleted HEK293 cells are hypersensitive to multiple
      types of DNA damage as well as chemically induced endoplasmic reticulum stress.
      Furthermore, using multiple routes to impair translation and mimic the effect of
      SBDS-depletion, we show that SBDS-dependent hypersensitivity of HEK293 cells to
      UV irradiation can be distinguished from a role of SBDS in translation. These
      results indicate functions of SBDS beyond ribosome biogenesis and may provide
      insight into the poorly understood cancer predisposition of SDS patients.

PMID- 19602487
TI  - Severe infections in HIV-exposed uninfected infants: clinical evidence of
      immunodeficiency.
AB  - We describe the clinical and basic immunological findings of eight HIV-exposed
      uninfected infants hospitalized with serious infectious morbidity and referred
      for immunological evaluation. The median age at presentation was 5.5 (1.5-15)
      months. Infections included Pneumocystis jiroveci pneumonia (three),
      cytomegalovirus colitis with perforation (one), Pseudomonas sepsis (two),
      hemorrhagic varicella (one) and Group A streptococcal meningitis and endocarditis
      (one). Five required intensive care, four for assisted ventilation and one for
      post-surgical care. Follow-up to 36 months suggested resolution of a transient
      immunodeficiency in two infants, one of whom had CD4 and the other B-cell
      depletion. Further studies are indicated in HIV-exposed uninfected infants.

PMID- 19602488
TI  - Adherence to oral rehydration therapy among in-patient children aged 1-59 months
      with some or no dehydration.
AB  - OBJECTIVE: To determine adherence to oral rehydration solution (ORS) among in
      patients aged 1-59 months suffering from gastroenteritis and having some
      dehydration (SD) or no dehydration (ND) in two rural hospitals in Kenya. METHODS:
      Children aged 1-59 months suffering from acute gastroenteritis with (SD) or (ND)
      were enrolled into the study, examined and medical records reviewed. On the
      second and third day of follow up, children were re-examined to ascertain
      hydration status and care-takers interviewed. RESULTS: Ninety-nine children were
      enrolled. Forty-five (75%) of the 60 children with SD received a correct
      prescription for ORS but only 12 (20%) received the correct amount. Among the 39
      children with ND, 23 (59%) received a correct prescription for ORS, however only
      16 (41%) received the correct amount. On the 3rd day, 9 (15%) of the 60 children
      with SD at baseline and 2 (5%) of the 39 with ND were classified as having SD.
      CONCLUSION: Four in five children with SD and 6 in 10 children with ND fail to
      receive the correct amounts of ORS.

PMID- 19602489
TI  - Evaluation of a 5-year programme to prevent mother-to-child transmission of HIV
      infection in Northern Uganda.
AB  - Prevention of mother-to-child transmission (PMTCT) is essential in HIV/AIDS
      control. We analysed 2000-05 data from mother-infant pairs in our PMTCT programme
      in rural Uganda, examining programme utilization and outcomes, HIV transmission
      rates and predictors of death or loss to follow-up (LFU). Out of 19,017 women,
      1,037 (5.5%) attending antenatal care services tested HIV positive. Of these, 517
      (50%) enrolled in the PMTCT programme and gave birth to 567 infants. Before
      tracing, 303 (53%) mother-infant pairs were LFU. Reasons for dropout were infant
      death and lack of understanding of importance of follow-up. Risk of death or LFU
      was higher among infants with no or incomplete intrapartum prophylaxis (OR =
      1.90, 95% CI 1.07-3.36) and of weaning age <6 months (OR 2.55, 95% CI 1.42-4.58),
      and lower in infants with diagnosed acute illness (OR 0.30, 95% CI 0.16-0.55).
      Mother-to-child HIV cumulative transmission rate was 8.3%, and 15.5% when HIV
      related deaths were considered. Improved tracking of HIV-exposed infants is
      needed in PMTCT programmes where access to early infant diagnosis is still
      limited.

PMID- 19602490
TI  - Effect of intraventricular dyssynchrony on diastolic function and exercise
      tolerance in patients with heart failure.
AB  - AIMS: Intraventricular dyssynchrony may contribute to the severity of heart
      failure [congestive heart failure (CHF)]. We assessed the correlates of
      intraventricular dyssynchrony and evaluated dyssynchrony as an independent
      predictive variable of exercise intolerance in CHF patients. METHODS AND RESULTS:
      Eighty-one CHF patients (66 +/- 9 years) underwent cardiopulmonary exercise test.
      Left ventricular (LV) diastolic function was evaluated by transmitral patterns
      and tissue Doppler. Intraventricular dyssynchrony was calculated according to
      time intervals between the onset of QRS and the onset of systolic velocities of
      basal septum and lateral wall. We divided the patients based on the mean value
      (40 ms) of dyssynchrony. Patients with intraventricular dyssynchrony (>40 ms)
      showed higher New York Heart Association class (2.7 +/- 0.6 vs. 2.2 +/- 0.4, P <
      0.001), higher brain natriuretic peptide (BNP) (415 +/- 478 vs. 194 +/- 205, P =
      0.014), more frequent restrictive transmitral pattern (33 vs. 7%, P = 0.013),
      higher E/E(a) (13 +/- 7 vs. 10 +/- 6, P = 0.016), lower mitral annulus peak
      systolic velocity (4.5 +/- 1.1 vs. 5.5 +/- 1.5 cm/s, P = 0.01), and peak oxygen
      consumption (13.8 +/- 3.5 vs. 18.1 +/- 3.9, P < 0.001), than patients without
      dyssynchrony (< or =40 ms). Predictors of exercise tolerance were
      intraventricular dyssynchrony (P = 0.035), log BNP (P = 0.003), and E/E(a) (P =
      0.004). CONCLUSION: Intraventricular dyssynchrony correlates with higher LV
      filling pressure and lower ejection fraction and it is an independent predictor
      of poor aerobic capacity; it may be helpful for functional evaluation of CHF
      patients.

PMID- 19602491
TI  - Is reduction aortoplasty (with or without external wrap) an acceptable
      alternative to replacement of the dilated ascending aorta?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether reduction aortoplasty is an
      acceptable alternative to ascending aorta replacement. From 925 potential papers,
      13 papers represented the best evidence to answer the clinical question. The
      authors, journal, date and country of publication, patient group studied, study
      type, relevant outcomes and results of these papers are tabulated. We conclude
      that aortoplasty seems to be a safe procedure which gives good postoperative
      outcomes in selected patients. Our literature review documents 716 patients from
      13 papers, with only 25 patients that on follow-up suffered redilatation (3%).
      Thus, reduction aortoplasty is a viable alternative to conventional aortic root
      replacement or interposition tube grafting in some patients. In particular, an
      aortoplasty in elderly patients with post-stenotic dilatation, or in patients
      with significant co-morbidities is attractive. It should be acknowledged that
      only one study directly compares the technique with conventional replacement and
      that replacement remains the 'gold standard' technique. It should also be
      acknowledged that the external wrap is not without risk and wrap dislocation,
      erosion or fistula formation are recognised complications.

PMID- 19602492
TI  - Video-assisted thoracic surgery major pulmonary resection requiring control of
      the main pulmonary artery.
AB  - The purpose of this study is to examine the feasibility and safety of
      thoracoscopic major pulmonary resection requiring the cross-clamping of the main
      pulmonary artery (PA), in comparison to an open thoracotomy performed in patients
      with lung cancer. A retrospective database of 27 consecutive lung cancer
      patients, who underwent either video-assisted thoracic surgery (VATS) (n=13) or
      open thoracotomy (n=14) for a major pulmonary resection using these procedures,
      was analyzed regarding the demographic, perioperative, histopathologic, and
      outcome variables. The thoracoscopic procedures were successfully performed in 12
      of 13 patients (92.3%). Two groups showed no differences in the demographic,
      perioperative, histopathologic and staging variables. Both groups presented with
      no mortality. The VATS group showed better results regarding the length of
      epidural anesthesia (P=0.0066), additional analgesic requirements (P=0.0009), and
      morbidity (P=0.0213) than the open thoracotomy group. Despite the short follow-up
      time, the two groups were comparable regarding both the recurrence and survival
      rates. The results indicate that VATS is feasible and safe for selected lung
      cancer patients requiring the cross-clamping of the main PA, with acceptable
      perioperative results in comparison to an open thoracotomy.

PMID- 19602493
TI  - Death in low-risk cardiac surgery: the failure to achieve a satisfactory cardiac
      outcome (FIASCO) study.
AB  - Death in low-risk patients is not studied as frequently as it is in other cardiac
      patients. We, therefore, sought to determine why some low-risk patients die after
      cardiac surgery. All low-risk patients (EuroSCORE<or=2) who died after cardiac
      surgery in one institution between 1996 and 2005 were included and meticulously
      studied by internal and independent external review of preoperative, operative
      and postoperative information from the case-notes and post-mortem findings.
      Deaths were classified into non-cardiac and cardiac and further subclassified
      into unavoidable deaths or due to failure in achieving a satisfactory cardiac
      outcome (FIASCO). Between 1996 and 2005, there were 16 deaths in 4294 low-risk
      patients (mortality 0.37%). Internal and external review agreed that nine deaths
      were non-preventable (CVA, bronchopneumonia, etc.) and that avoidable FIASCO
      accounted for seven deaths. Of the deaths considered to be preventable, all had
      probable errors of technique and three also had additional system errors. No
      cardiac operation is without risk. Mortality, though fortunately rare, can still
      occur, even in low-risk patients. Despite an extremely low mortality in the low
      risk group FIASCO still accounts for nearly one-half of deaths. This suggests
      that mortality may be reduced even further as part of a quality improvement
      programme.

PMID- 19602494
TI  - Acute mechanical prosthetic valve thrombosis after initiating oral
      anticoagulation therapy. Is bridging anticoagulation with heparin required?
AB  - Prosthetic valve thrombosis (PVT) represents a serious and potentially lethal
      complication. It can be attributed more frequently to inadequate anticoagulant
      therapy. We present a case of acute aortic mechanical valve thrombosis six months
      after implantation. The patient discontinued oral anticoagulation after being
      discharged following the primary operation. Two days after reinitiating warfarin
      as an outpatient, he developed acute valve thrombosis presenting with symptoms
      and signs of cardiac failure. He was managed with intravenous thrombolysis with a
      recombinant plasminogen activator which resulted in immediate resolution of
      thrombus and clinical improvement. A paradox procoagulant effect of warfarin is
      evident on the first one or two days after initiation of therapy. A 'bridging'
      protocol with unfractionated or low molecular weight heparin (LMWH) should be
      considered, according to recently published guidelines, until warfarin reaches
      therapeutic levels and exerts an antithrombotic effect.

PMID- 19602495
TI  - Spontaneous left main coronary artery dissection, possibly due to cystic medial
      necrosis found in the internal mammary arteries.
AB  - A 55-year-old male without previous medical history developed chest pain.
      Coronary catheterization showed left main coronary dissection. Coronary artery
      bypass grafting was performed using bilateral internal mammary arteries, which
      were very fragile. The specimens of the internal mammary arteries sent for
      pathology showed cystic medial necrosis.

PMID- 19602496
TI  - Post-sternotomy intercostal artery pseudoaneurysm. Sonographic diagnosis and
      thrombosis by ultrasound-guided percutaneous thrombin injection.
AB  - Intercostal artery pseudoaneurysms are extremely rare. We present a case of an
      intercostal artery pseudoaneurysm after median sternotomy that was treated by
      ultrasound-guided percutaneous thrombin injection. They are a potential source of
      complications, especially haemothorax, and treatment is mandatory. Different
      methods may be used for the confirmatory diagnosis of false aneurysms. Doppler
      ultrasound (DUS) and CT are the two most commonly used methods, but
      pseudoaneurysms have also been diagnosed by means of arteriography (AR), which
      enables endovascular treatment of the pseudoaneurysm in a single procedure. We
      used Doppler sonography alone, because this technique yielded a definitive
      diagnosis without the need for other complementary imaging modalities to treat
      the lesion. There are various possible treatments for lesions of this kind.
      Endovascular embolization is the commonly used treatment for intercostal
      pseudoaneurysm but also stent grafting has been described. Surgical
      aneurysmectomy with proximal ligation of the intercostal artery is an option
      described for the treatment of the pseudoaneurysm. To date only seven cases have
      been published in the literature. Our case is the only published instance of
      treatment of an intercostal artery pseudoaneurysm by direct percutaneous thrombin
      injection under sonographic guidance.

PMID- 19602497
TI  - Low incidence of bronchopleural fistula after pneumonectomy for lung cancer.
AB  - Bronchopleural fistula (BPF) after pneumonectomy for NSCLC remains a highly
      morbid complication. We examined possible factors including the surgical
      techniques associated with BPF development. From 221 pneumonectomies for NSCLC,
      bronchial stump closure was mechanically performed in 192 patients and manually
      in the remaining 29. In all right-sided pneumonectomies mechanical closure was
      performed with associated stump coverage. In 114/130 left-sided procedures where
      mechanical closure was selected, bronchial stump remained uncovered. In the
      remaining 16 left-sided cases where manual stump closure was selectively
      performed, the stump was covered utilizing various tissues. Risk factors were
      classified into preoperative, intra-operative and postoperative. Five patients
      (2.3%) developed BPF. Univariate analysis revealed peri-operative transfusion,
      respiratory infection at the time of presentation, neoadjuvant therapy, right
      sided pneumonectomy, manual type of bronchial closure, days of postoperative
      hospitalization and mechanical ventilation as significant risk factors for BPF
      development. Multivariate analysis followed revealing preoperative respiratory
      infection and right pneumonectomy as the only independent risk factors. In our
      series, a selected stump coverage policy showed a low incidence of BPF
      development. Mechanical stapling was superior to manual closure, although not as
      an independent factor. Early recognition of possible risk factors associated with
      fistula development is of paramount importance.

PMID- 19602498
TI  - Estimation of the relative sizes of rate constants for chlorophyll de-excitation
      processes through comparison of inverse fluorescence intensities.
AB  - The paper derives a simple way to calculate the linear relationships between all
      separable groups of rate constants for de-excitation of Chl a excitation energy.
      This is done by comparison of the inverse values of chlorophyll fluorescence
      intensities and is based on the matrix model of Kitajima and Butler and on the
      lake model of energy exchange among PSII centers. Compared with the outputs of
      earlier, similar calculations, the results presented here add some linear
      comparisons of the relative sizes of rate constants without the need for F(0)'
      measurement. This enables us to regenerate the same alternative formula to
      calculate q(L) as presented previously, in a different and simple form. The same
      former equation to calculate F(0)' value from F(m), F(m)' and F(0) values is also
      regenerated in our calculation system in a simple form. We also apply relaxation
      analysis to separate the rate constant for non-photochemical quenching (k(NPQ))
      into the rate constant for a fast-relaxing non-photochemical quenching (k(fast))
      and the rate constant for slow-relaxing non-photochemical quenching (k(slow)).
      Changes in the sizes of rate constants were measured in Arabidopsis thaliana and
      in rice.

PMID- 19602499
TI  - Auxin amidohydrolases from Brassica rapa cleave the alanine conjugate of
      indolepropionic acid as a preferable substrate: a biochemical and modeling
      approach.
AB  - Two auxin amidohydrolases, BrIAR3 and BrILL2, from Chinese cabbage [Brassica rapa
      L. ssp. pekinensis (Lour.) Hanelt] were produced by heterologous expression in
      Escherichia coli, purified, and screened for activity towards N-(indol-3
      ylacetyl)-L-alanine (IAA-Ala) and the long-chain auxin-amino acid conjugates, N
      [3-(indol-3-yl)propionyl]-L-alanine (IPA-Ala) and N-[4-(indol-3-yl)butyryl]-L
      alanine (IBA-Ala). IPA-Ala was shown to be the favored substrate of both enzymes,
      but BrILL2 was approximately 15 times more active than BrIAR3. Both enzymes
      cleaved IBA-Ala and IAA-Ala to a lesser extent. The enzyme kinetics were measured
      for BrILL2 and the obtained parameters suggested similar binding affinities for
      the long-chain auxin-amino acid conjugates (IPA-Ala and IBA-Ala). The velocity of
      the hydrolyzing reaction decreased in the order IPA-Ala > IBA-Ala > IAA-Ala. In a
      root growth bioassay, higher growth inhibition was caused by IPA-Ala and IBA-Ala
      in comparison with IAA-Ala. Neither these conjugates nor the corresponding free
      auxins affected the expression of the BrILL2 gene. A modeling study revealed
      several possible modes of IPA-Ala binding to BrILL2. Based on these results, two
      possible scenarios for substrate hydrolysis are proposed. In one the metal
      binding water is activated by the carboxyl group of the substrate itself, and in
      the other by a glutamate residue from the active site of the enzyme.

PMID- 19602501
TI  - Trends in wood dust inhalation exposure in the UK, 1985-2005.
AB  - OBJECTIVES: Wood dust data held in the Health and Safety Executive (HSE) National
      Exposure DataBase (NEDB) were reviewed to investigate the long-term changes in
      inhalation exposure from 1985 to 2005. In addition, follow-up sampling
      measurements were obtained from selected companies where exposure measurements
      had been collected prior to 1994, thereby providing a follow-up period of at
      least 10 years, to determine whether changes in exposure levels had occurred,
      with key staff being interviewed to identify factors that might be responsible
      for any changes observed. METHODS: Analysis of the temporal trend in exposure
      concentrations was performed using Linear Mixed Effect Models on the log
      transformed NEDB data set and expressed as the relative annual change in
      concentration. RESULTS: For the NEDB wood dust data, an annual decline of
      geometric mean (GM) exposure of 8.1% per year was found based on 1459 exposure
      measurements collected between 1985 and 2003. This trend was predominantly
      observed in data from inspection visits (measurements collected on a mandatory
      basis by a Specialist HSE Inspector) (n = 1009), while data from representative
      surveys (measurements collected on a voluntary basis to provide information on
      current practices and exposures) remained relatively stable. Ten follow-up
      surveys in individual workplaces in 2004-2005 resulted in 70 new measurements and
      for each of the companies resurveyed, the GM of the wood dust exposure decreased
      between sampling surveys. CONCLUSION: Analysis of the temporal trend in UK wood
      dust exposure concentrations revealed declines of 8% per annum. Interviews with
      key long-serving employees and management suggest that factors such as
      technological changes in production processes, response to new legislation, and
      enforcement agency inspections, together with global economic trends, could be
      linked to the downward trends observed.

PMID- 19602500
TI  - Investigation of PAH biomarkers in the urine of workers exposed to hot asphalt.
AB  - Airborne emissions from hot asphalt contain mixtures of polycyclic aromatic
      hydrocarbons (PAHs), including several carcinogens. We investigated urinary
      biomarkers of three PAHs, namely naphthalene (Nap), phenanthrene (Phe), and
      pyrene (Pyr) in 20 road-paving workers exposed to hot asphalt and in 6 road
      milling workers who were not using hot asphalt (reference group). Our analysis
      included baseline urine samples as well as postshift, bedtime, and morning
      samples collected over three consecutive days. We measured unmetabolized Nap (U
      Nap) and Phe (U-Phe) as well as the monohydroxylated metabolites of Nap (OH-Nap),
      Phe (OH-Phe), and Pyr (OH-Pyr) in each urine sample. In baseline samples, no
      significant differences in biomarker levels were observed between pavers and
      millers, suggesting similar background exposures. In postshift, bedtime, and
      morning urine samples, the high pairwise correlations observed between levels of
      all biomarkers suggest common exposure sources. Among pavers, levels of all
      biomarkers were significantly elevated in postshift samples, indicating rapid
      uptake and elimination of PAHs following exposure to hot asphalt (biomarker
      levels were not elevated among millers). Results from linear mixed-effects models
      of levels of U-Nap, U-Phe, OH-Phe, and OH-Pyr across pavers showed significant
      effects of work assignments with roller operators having lower biomarker levels
      than the other workers. However, no work-related effect was observed for levels
      of OH-Nap, apparently due to the influence of cigarette smoking. Biological half
      lives, estimated from regression coefficients for time among pavers, were 8 h for
      U-Phe, 10 h for U-Nap, 13 h for OH-Phe and OH-Pyr, and 26 h for OH-Nap. These
      results support the use of U-Nap, U-Phe, OH-Phe, and OH-Pyr, but probably not OH
      Nap, as short-term biomarkers of exposure to PAHs emanating from hot asphalt.

PMID- 19602502
TI  - Comparing urinary biomarkers of airborne and dermal exposure to polycyclic
      aromatic compounds in asphalt-exposed workers.
AB  - When working with hot mix asphalt, road pavers are exposed to polycyclic aromatic
      hydrocarbons (PAHs) through the inhalation of vapors and particulate matter (PM)
      and through dermal contact with PM and contaminated surfaces. Several PAHs with
      four to six rings are potent carcinogens which reside in these particulate
      emissions. Since urinary biomarkers of large PAHs are rarely detectable in
      asphalt workers, attention has focused upon urinary levels of the more volatile
      and abundant two-ring and three-ring PAHs as potential biomarkers of PAH
      exposure. Here, we compare levels of particulate polycyclic aromatic compounds (P
      PACs, a group of aromatic hydrocarbons containing PAHs and heterocyclic compounds
      with four or more rings) in air and dermal patch samples from 20 road pavers to
      the corresponding urinary levels of naphthalene (U-Nap) (two rings), phenanthrene
      (U-Phe) (three rings), monohydroxylated metabolites of naphthalene (OH-Nap) and
      phenanthrene (OH-Phe), and 1-hydroxypyrene (OH-Pyr) (four rings), the most widely
      used biomarker of PAH exposure. For each worker, daily breathing-zone air (n =
      55) and dermal patch samples (n = 56) were collected on three consecutive
      workdays along with postshift, bedtime, and morning urine samples (n = 149).
      Measured levels of P-PACs and the urinary analytes were used to statistically
      model exposure-biomarker relationships while controlling for urinary creatinine,
      smoking status, age, body mass index, and the timing of urine sampling. Levels of
      OH-Phe in urine collected postshift, at bedtime, and the following morning were
      all significantly associated with levels of P-PACs in air and dermal patch
      samples. For U-Nap, U-Phe, and OH-Pyr, both air and dermal patch measurements of
      P-PACs were significant predictors of postshift urine levels, and dermal patch
      measurements were significant predictors of bedtime urine levels (all three
      analytes) and morning urine levels (U-Nap and OH-Pyr only). Significant effects
      of creatinine concentration were observed for all analytes, and modest effects of
      smoking status and body mass index were observed for U-Phe and OH-Pyr,
      respectively. Levels of OH-Nap were not associated with P-PAC measurements in air
      or dermal patch samples but were significantly affected by smoking status, age,
      day of sample collection, and urinary creatinine. We conclude that U-Nap, U-Phe,
      OH-Phe, and OH-Pyr can be used as biomarkers of exposure to particulate asphalt
      emissions, with OH-Phe being the most promising candidate. Indications that
      levels of U-Nap, U-Phe, and OH-Pyr were significantly associated with dermal
      patch measurements well into the evening after a given work shift, combined with
      the small ratios of within-person variance components to between-person variance
      components at bedtime, suggest that bedtime measurements may be useful for
      investigating dermal PAH exposures.

PMID- 19602506
TI  - Commentary. Endovascular management of atherosclerotic renovascular disease:
      early results following primary intervention.

PMID- 19602503
TI  - Arrhythmias and increased neuro-endocrine stress response during physicians'
      night shifts: a randomized cross-over trial.
AB  - AIMS: To evaluate the effects of a 24 h (h) physicians on-call duty (OCD) ('night
      shift') on 24 h electrocardiogram (ECG), heart rate variability, blood pressure
      (BP), and various biochemical serum and urine 'stress markers' compared with a
      'regular' day at work. METHODS AND RESULTS: The study was designed as a
      prospective randomized cross-over trial with each physician completing a 24 h (h)
      OCD and a 24 h control period including a regular 8 h non-OCD. Thirty healthy
      physicians with a median age of 33.5 years (range 29.0-45.0) were analysed.
      Twenty-four hours ECG and BP monitoring were performed and participants were
      instructed to fill out an event diary and perform a 24 h urine collection.
      Furthermore, blood was drawn before and after OCD and control day. Twenty-four
      hours ECG showed a higher rate of ventricular premature beats (VPB) during early
      morning hours (VPB 0-6 h, 0.5 vs. 0.0, P = 0.047) and increased low-frequency
      normalized units (29.3 vs. 25.5, P = 0.050) during night shift when compared with
      respective control night at home. During OCD, BP monitoring revealed a greater
      diastolic BP throughout 24 h (83.5 vs. 80.2 mmHg, P = 0.025) as well as during
      night-time (75.4 vs. 73.0, P = 0.028) associated with a higher rate of systolic
      BP more than 125 mmHg during sleep time. Tumour necrosis factor alpha
      concentrations increased significantly during night shift (0.76 vs. 0.05 pg/mL, P
      = 0.045). Urinary noradrenaline excretion was greater during OCD when compared
      with control day (46.0 vs. 36.0 microg/24 h, P = 0.007). CONCLUSION: Our results
      highlight the association of OCD with an increased risk profile for
      cardiovascular disease. In addition to the acute effects observed, frequent night
      calls over a longer period possibly elicit sustained alterations in
      cardiovascular homeostasis.

PMID- 19602507
TI  - The ESCHAR trial: should it change practice?
AB  - INTRODUCTION: Most leg ulcers are caused by venous disease, the most common cause
      of venous hypertension being superficial vein incompetence. The ESCHAR trial
      tested the value of superficial vein surgery combined with compression in the
      healing and recurrence of venous leg ulcers compared with compression alone.
      METHODS: A total of 500 patients with chronic venous leg ulcers, or recently
      healed ulcers, were randomized to superficial vein surgery and compression or
      compression alone. Vein surgery was saphenofemoral ligation and great saphenous
      stripping and phlebectomy or saphenopopliteal ligation and phlebectomy. RESULTS:
      Ulcer healing was virtually identical between the 2 groups at 65% at 24 weeks;
      subgroup analysis failed to show a benefit for surgery to promote ulcer healing.
      Ulcer recurrence rate was halved in those that underwent surgery regardless of
      the presence of deep vein incompetence. CONCLUSION: Superficial vein surgery
      should be considered in all leg ulcer sufferers to reduce ulcer recurrence rather
      than accelerate ulcer healing.

PMID- 19602508
TI  - An RNA spiking method demonstrates that 18S rRNA is regulated by progesterone in
      the mouse uterus.
AB  - Identifying suitable housekeeping genes for quantitative RT-PCR in the uterus is
      problematic, as this tissue undergoes significant structural and functional
      alterations during the oestrous cycle and pregnancy in response to circulating
      hormones. The suitability of 18S rRNA as a housekeeping gene in mouse uterus was
      investigated by introducing an 'RNA spike' standard into the reverse
      transcription reaction. 18S rRNA levels increased by Day 4 of pregnancy and after
      progesterone administration in ovariectomized mice. We conclude that 18S rRNA is
      not a suitable housekeeping gene for quantitative RT-PCR analysis in progesterone
      responsive tissues, and the RNA spiking method provides a suitable alternative.

PMID- 19602509
TI  - Mutations in the protamine locus: association with spermatogenic failure?
AB  - The protamine locus consists of a 28.5 kb region with a linear array of the
      protamine (PRM)1, PRM2, PRM3 and transition nuclear protein (TNP)2 genes. Several
      studies indicate an abnormal expression pattern of protamine genes associated
      with male infertility, although the molecular mechanism underlying this
      observation is unclear. Here, we determined the spectrum of DNA variants present
      in all four genes in men with unexplained infertility compared with an ancestry
      matched fertile/normospermic population. A total of 160 control individuals and
      at least 125 infertile men with either idiopathic azoospermia or oligozoospermia
      were sequenced for the open reading frame of PRM1, PRM2, PRM3 and TNP2 genes. All
      individuals carried an apparently intact Y chromosome. Of the 28 variants
      identified, 21 were previously described in the literature. The novel variants
      that were observed only in the infertile cohort included the SNP c.65G>A mutation
      which resulted in an amino acid change at the codon 22 (p.Ser22Asn) in the PRM1
      gene, a mutation in the promoter region of PRM2 (-67C>T) and a nonsense mutation
      in the PRM3 gene. These data are consistent with that of previous studies which
      have indicated that mutations in the protamine locus may be an infrequent cause
      of male infertility.

PMID- 19602510
TI  - Gene looping is conferred by activator-dependent interaction of transcription
      initiation and termination machineries.
AB  - Gene looping juxtaposes the promoter and terminator regions of RNA polymerase II
      transcribed genes in yeast and mammalian cells. Here we report an activator
      dependent interaction of transcription initiation and termination factors during
      gene looping in budding yeast. Chromatin analysis revealed that MET16, INO1, and
      GAL1p-BUD3 are in a stable looped configuration during activated transcription.
      Looping was nearly abolished in the absence of transcription activators Met28,
      Ino2, and Gal4 of MET16, INO1, and GAL1p-BUD3 genes, respectively. The activator
      independent increase in transcription was not accompanied by loop formation,
      thereby suggesting an essential role for activators in gene looping. The
      activators did not facilitate loop formation directly because they did not
      exhibit an interaction with the 3' end of the genes. Instead, activators
      physically interacted with the general transcription factor TFIIB when the genes
      were activated and in a looped configuration. TFIIB cross-linked to both the
      promoter and the terminator regions during the transcriptionally activated state
      of a gene. The presence of TFIIB on the terminator was dependent on the Rna15
      component of CF1 3' end processing complex. Coimmunoprecipitation revealed a
      physical interaction of Rna15 with TFIIB. We propose that the activators
      facilitate gene looping through their interaction with TFIIB during
      transcriptional activation of genes.

PMID- 19602512
TI  - Defective chromatin structure in somatic cell cloned mouse embryos.
AB  - Epigenetic reprogramming plays a central role in the development of cloned
      embryos generated by somatic cell nuclear transfer, and it is believed that
      aberrant reprogramming leads to the abnormal development of most cloned embryos.
      Recent studies show that trimethylation of H3K27 (H3K27me3) contributes to the
      maintenance of embryonic stem cell pluripotency because the differentiation genes
      are always occupied by nucleosomes trimethylated at H3K27, which represses gene
      expression. Here, we provide evidence that differential H3K27me3 modification
      exists between normal fertilization-produced blastocysts and somatic cell nuclear
      transfer cloned blastocysts; H3K27me3 was specifically found in cells of the
      inner cell mass (ICM) of normal blastocysts, whereas there was no modification of
      H3K27me3 in the ICM of cloned blastocysts. Subsequently, we demonstrated that the
      differentiation-related genes, which are marked by H3K27me3 in embryonic stem
      cells, were expressed at significantly higher levels in cloned embryos than in
      normal embryos. The polycomb repressive complex 2 (PRC2) component genes (Eed,
      Ezh2, and Suz12), which are responsible for the generation of H3K27me3, were
      expressed at lower levels in the cloned embryos. Our results suggest that reduced
      expression of PRC2 component genes in cloned embryos results in defective
      modification of H3K27me3 to the differentiation-related genes in pluripotent ICM
      cells. This results in premature expression of developmental genes and death of
      somatic cloned embryos shortly after implantation. Taken together, these studies
      suggest that H3K27me3 might be an important epigenetic marker with which to
      evaluate the developmental potential of cloned embryos.

PMID- 19602513
TI  - Hyperglycaemia in acute ischaemic stroke is associated with an increased 5-year
      mortality.
AB  - BACKGROUND: admission hyperglycaemia (HG) is associated with worse prognosis and
      higher mortality within 3 months after stroke. Reports on long-term mortality are
      inconsistent. OBJECTIVE: to evaluate the influence of admission HG [blood glucose
      (BG) levels >8 mmol/L] on long-term mortality after ischaemic stroke (IS) and
      transient ischaemic attack (TIA). METHODS: consecutive patients with IS or TIA,
      admitted from January 1997 until December 2002, were retrospectively screened. BG
      was measured within 3 days from onset of symptoms. Information on the date of
      death was obtained within 10 years after onset. RESULTS: a total of 509 patients
      (78% IS; 22% TIA) were included. Admission HG was present in 28% and 18% of the
      IS and TIA patients, respectively (P = 0.05). Mean admission BG was 7.6 +/- 3.2
      mmol/L in the IS and 6.7 +/- 2.3 mmol/L in TIA (P = 0.002). During a mean
      observation of 66 +/- 35 months, the overall 1- and 10-year mortality rate was
      12% and 51% in IS compared to 4% and 38% in TIA patients (P = 0.004).
      Normoglycaemic IS patients had a longer median survival than those with HG (113
      vs 84 months, P = 0.04). Admission HG did not affect the mortality rates in TIA
      patients. CONCLUSION: admission HG is associated with greater mortality rates up
      to 5 years after stroke but does not influence the survival of TIA patients.

PMID- 19602514
TI  - Clostridium difficile-associated diarrhoea (CDAD): new and contentious issues.

PMID- 19602511
TI  - Copper transport in mammalian cells: special care for a metal with special needs.
AB  - Copper plays an essential role in human physiology. It is required for
      respiration, radical defense, neuronal myelination, angiogenesis, and many other
      processes. Copper has distinct physicochemical properties that pose uncommon
      challenges for its transport across biological membranes. Only small amounts of
      copper are present in biological fluids, and essentially none of it exists in a
      free ion form. These properties and the low redox potential of copper dictate
      special structural and mechanistic features in copper transporters. This
      minireview discusses molecular mechanisms through which copper enters and exits
      human cells.

PMID- 19602515
TI  - A simple and efficient cryopreservation method for feeder-free dissociated human
      induced pluripotent stem cells and human embryonic stem cells.
AB  - BACKGROUND: An essential prerequisite for the future widespread application of
      human induced pluripotent (hiPSCs) and embryonic stem cells (hESCs) is the
      development of efficient cryopreservation methods to facilitate their storage and
      transportation. METHODS: We developed a simple and effective freezing/thawing
      method of single dissociated hESCs and hiPSCs in a feeder-free culture in the
      presence of Rho-associated kinase (ROCK) inhibitor Y-27632. RESULTS: Exposure to
      ROCK inhibitor Y-27632 in freezing solution alone does not significantly enhance
      the post-thaw survival rate of single dissociated hESCs and hiPSCs. However, when
      ROCK inhibitor was added to both pre- and post-thaw culture media, there was an
      enhancement in the survival rate, which further increased when ROCK inhibitor was
      added to Matrigel as well. Under these treatments, hESCs and hiPSCs retained
      typical morphology, stable karyotype, expression of pluripotency markers and the
      potential to differentiate into derivatives of all three germ layers after long
      term culture. CONCLUSIONS: This method is an effective cryopreservation procedure
      for single dissociated hESCs in feeder-free culture, which is also applicable for
      single dissociated hiPSCs using a ROCK inhibitor. The cloning efficiency of
      hiPSCs and hESCs improves when ROCK inhibitor is added both in Matrigel and in
      medium in comparison with conventional addition to medium. Therefore, we believe
      this method would be useful for current and future applications of the
      pluripotent stem cells.

PMID- 19602516
TI  - Y chromosome gr/gr deletions are a risk factor for low semen quality.
AB  - BACKGROUND: Subfertility affects one in eight couples. In up to 50% of cases, the
      male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia
      factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are
      established causes of low semen quality. Whether a recently identified partial
      AZFc deletion, the gr/gr deletion, also causes low semen quality is at present
      unclear. METHODS: We used a dual approach to review the effect of the gr/gr
      deletion on semen quality. First, we conducted a systematic review and meta
      analysis of previous association studies, to compare the prevalence of gr/gr
      deletions between azoo-/oligozoospermic men and normozoospermic men. Secondly, we
      studied a cohort of 1041 male partners of subfertile couples unselected for semen
      quality. We employed a cross-sectional design by screening all men for the gr/gr
      deletion and comparing the semen quality of men with and without the gr/gr
      deletion. RESULTS: Seven studies were included in the meta-analysis. The gr/gr
      deletion was significantly more prevalent among azoo-/oligozoospermic men than
      among normozoospermic men (OR 2.4, 95% CI 1.75-3.30). In our cohort, 25 men
      carried a gr/gr deletion. Men with this genotype had a lower sperm concentration
      (median 34 x 10(6)/ml versus 53 x 10(6)/ml, P = 0.017), total sperm count (median
      108 x 10(6) versus 152 x 10(6), P = 0.006) and total motile sperm count (median
      20 x 10(6) versus 50 x 10(6), P = 0.010) than men without the gr/gr deletion.
      CONCLUSION: Y chromosome gr/gr deletions significantly reduce sperm counts and
      are thus associated with low semen quality.

PMID- 19602517
TI  - Interleukin-2 receptor beta gene C627T polymorphism in Korean women with
      endometriosis: a case-control study.
AB  - BACKGROUND: The purpose of this study was to investigate the potential
      association of the C627T polymorphism in the interleukin-2 receptor beta gene (IL
      2R beta) with the risk of endometriosis in Korean women. METHODS: Two hundred and
      thirty-seven women with surgically or histologically diagnosed endometriosis of
      stages III and IV were recruited for this study, and 164 patients with no
      evidence of endometriosis diagnosed by laparoscopy or laparotomy served as
      controls. The C627T polymorphism of the IL-2R beta was assessed using the TaqMan
      allelic discrimination assay. Chi2 analysis was used to examine any differences
      in genotype distributions and allele frequencies of the IL-2R beta C627T
      polymorphism between the endometriosis cases and the controls. RESULTS: There was
      no statistically significant difference in the frequency of the IL-2R beta C627T
      polymorphism between the endometriosis patients and the controls (28.7% C/C,
      48.1% C/T and 23.2% T/T versus 29.3, 44.5 and 26.2%, respectively, P = 0.72) or
      in the T allele frequencies (47.3 versus 48.5%, respectively, P = 0.73). Even
      when the endometriosis cases were subdivided into stages III and IV, no
      statistically significant differences in genotype distributions or allele
      frequencies were observed among the three groups. CONCLUSIONS: Contrary to the
      recent data reported in a Taiwanese population, our results suggest that the
      C627T polymorphism of the IL-2R beta gene may not be associated with the risk of
      endometriosis in the Korean population.

PMID- 19602518
TI  - Individual versus standard dose of rFSH in a mild stimulation protocol for
      intrauterine insemination: a randomized study.
AB  - BACKGROUND: Controlled ovarian stimulation (COS) and intrauterine insemination
      (IUI) are often used as the first-line treatment for subfertile couples. To
      minimize the variability in ovarian response in patients' first treatment cycle,
      we recently developed a recombinant follicle-stimulating hormone (rFSH) dosage
      nomogram. The nomogram has now been tested. METHODS: Multicentre randomized
      controlled trial (RCT) including 228 ovulatory patients scheduled for COS and
      IUI. Patients were randomized to 'individual' (50-100 IU rFSH/day, n = 113) or
      'standard' (75 IU rFSH/day, n = 115) dose. 'Individual' dose was prescribed
      according to the nomogram, which was based on patients' body weight and antral
      follicle count. The primary end-point was the proportion of patients with two to
      three follicles > or = 14 mm (maximum two follicles > or = 18 mm) on the day of
      hCG (leading follicle = 18 mm). Primary analysis was made by intention-to-treat.
      RESULTS: In the 'individual' group, 79/113 (70%) of the patients developed two to
      three follicles versus 64/115 (56%) in the 'standard' group [absolute difference
      = 14.3 percentage points; 95% confidence interval (CI) 2-26, P = 0.03; absolute
      difference = 14.4; 95% CI 2-27, P = 0.02, when adjusting for centre]. Among
      patients with two to three follicles, the proportion of patients with two
      follicles was 46/79 (58%) in the 'individual' group versus 34/64 (53%) in the
      'standard' group, P = 0.54. Ongoing pregnancy rate was 23/113 (20%) in the
      'individual' group and 21/115 (18%) in the 'standard' group and the rate of
      multiple gestations was 1/113 (1%) versus 5/115 (4%), P = 0.21. CONCLUSIONS: This
      RCT is the first to clinically test a dosage nomogram in ovulatory IUI patients'
      first rFSH treatment cycle. Dosing according to the nomogram was superior to
      standard dosing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00374634.

PMID- 19602520
TI  - Mothers' experiences of bottle-feeding: a systematic review of qualitative and
      quantitative studies.
AB  - OBJECTIVE: Most babies receive at least some formula milk. Variations in formula
      feeding practices can have both short- and long-term health consequences. The
      literature on parents' experiences of bottle-feeding was systematically reviewed
      to understand how formula-feeding decisions are made. METHODS: Relevant English
      language papers, identified by searching 12 electronic databases, reference lists
      and related articles and by contacting first authors of included papers, were
      systematically searched for and appraised. The included studies were analysed and
      synthesised using a combination of narrative and thematic approaches. Consensus
      on the final inclusion, interpretation and synthesis of studies was reached
      across the research team. RESULTS: Six qualitative studies and 17 quantitative
      studies (involving 13 263 participants) were included. Despite wide differences
      in study design, context, focus and quality, several consistent themes emerged.
      Mothers who bottle-fed their babies experienced negative emotions such as guilt,
      anger, worry, uncertainty and a sense of failure. Mothers reported receiving
      little information on bottle-feeding and did not feel empowered to make
      decisions. Mistakes in preparation of bottle-feeds were common. No studies
      examined how mothers made decisions about the frequency or quantity of bottle
      feeds. CONCLUSIONS: Inadequate information and support for mothers who decide to
      bottle-feed may put the health of their babies at risk. While it is important to
      promote breastfeeding, it is also necessary to ensure that the needs of bottle
      feeding mothers are met.

PMID- 19602521
TI  - Characterization of inhibin alpha subunit (inha) in the zebrafish: evidence for a
      potential feedback loop between the pituitary and ovary.
AB  - Inhibin and activin are closely related disulphide-linked dimers that belong to
      the transforming growth factor beta superfamily. Although inhibin has been
      extensively studied in mammals, the information about its existence and function
      in lower vertebrates is very scarce. Using zebrafish as a model, the present
      study demonstrated that the inhibin-specific alpha subunit (inha) was
      predominantly expressed in the gonads and no transcript could be detected in
      other tissues including the pituitary and brain. In the ovary, the expression of
      inha was restricted to the somatic follicle cells surrounding the oocyte,
      together with the beta subunits (inhbaa and inhbb). This was further supported by
      the absence of its expression in the ovulated unfertilized eggs. During
      folliculogenesis, inha expression in the follicles slightly but steadily
      increased from primary growth to the mid-vitellogenic stage; however, its
      expression surged dramatically at the full-grown stage. Interestingly, the
      expression level of inha decreased significantly in the follicles whose oocytes
      were undergoing spontaneous maturation or germinal vesicle breakdown. When tested
      on cultured ovarian fragments, both goldfish pituitary extract and forskolin
      significantly stimulated inha expression. Further experiments showed that
      recombinant zebrafish FSH but not LH significantly increased inha expression in
      the same assay system. When tested in vitro, human inhibin A exhibited a slight
      but significant inhibitory effect on 17alpha, 20beta-dihydroxyprogesterone
      induced oocyte maturation after 4 h incubation. The stimulation of inha
      expression by FSH and the potential inhibition of FSH by inhibin suggest a
      possible existence of a negative feedback loop between the pituitary and ovary in
      the zebrafish.

PMID- 19602523
TI  - Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.
AB  - Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male
      sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown.
      In this study, we analyzed in more detail the testicular phenotype of TAM triple
      mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate
      that the three TAM RTKs cooperatively regulate male fertility, and MER appears to
      be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss
      of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-)
      mice exhibited oligo-astheno-teratozoospermia and various morphological
      malformations of sperm cells. As the mice aged, the germ cells were eventually
      depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-)
      Sertoli cells have an impaired phagocytic activity and a large number of
      differentially expressed genes compared to wild-type controls. By contrast, the
      function of Leydig cells was not apparently affected by the mutation of TAM RTKs.
      Therefore, we conclude that the suboptimal function of Sertoli cells leads to the
      impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into
      the mechanism of TAM RTKs in regulating male fertility.

PMID- 19602522
TI  - Cumulus gene expression as a predictor of human oocyte fertilisation, embryo
      development and competence to establish a pregnancy.
AB  - The close relationship between cumulus cell function and oocyte developmental
      competence indicates that analysis of cumulus gene expression is a potential non
      invasive method to aid embryo selection and IVF outcome. Cumulus was isolated
      from 674 oocytes from 75 women undergoing ICSI and gene expression analysed by
      quantitative RT-PCR. Cumulus expression of cyclooxygenase 2 (PTGS2) was higher
      with mature oocytes, whereas brain-derived neurotrophic factor (BDNF) was lower
      when fertilisation was normal. Expression levels of gremlin (GREM1) and BDNF were
      weak positive and negative predictors of embryo quality respectively. Ranking of
      GREM1 expression within cohorts of oocytes showed that oocytes associated with
      the highest GREM1 expression were more likely to be transferred or cryopreserved
      than discarded (49 vs 33%, P<0.02), although the clinical pregnancy rate was not
      significantly different. This study demonstrates both the feasibility and
      difficulties of this method of analysis in the largest such group studied thus
      far. Novel relationships between BDNF expression and fertilisation were
      identified, and the potential value of GREM1 expression as a marker of embryo
      quality supports the further assessment of GREM1 analysis in the context of
      embryo selection.

PMID- 19602524
TI  - Normalization of peak intensities in bottom-up MS-based proteomics using singular
      value decomposition.
AB  - MOTIVATION: LC-MS allows for the identification and quantification of proteins
      from biological samples. As with any high-throughput technology, systematic
      biases are often observed in LC-MS data, making normalization an important
      preprocessing step. Normalization models need to be flexible enough to capture
      biases of arbitrary complexity, while avoiding overfitting that would invalidate
      downstream statistical inference. Careful normalization of MS peak intensities
      would enable greater accuracy and precision in quantitative comparisons of
      protein abundance levels. RESULTS: We propose an algorithm, called EigenMS, that
      uses singular value decomposition to capture and remove biases from LC-MS peak
      intensity measurements. EigenMS is an adaptation of the surrogate variable
      analysis (SVA) algorithm of Leek and Storey, with the adaptations including (i)
      the handling of the widespread missing measurements that are typical in LC-MS,
      and (ii) a novel approach to preventing overfitting that facilitates the
      incorporation of EigenMS into an existing proteomics analysis pipeline. EigenMS
      is demonstrated using both large-scale calibration measurements and simulations
      to perform well relative to existing alternatives. AVAILABILITY: The software has
      been made available in the open source proteomics platform DAnTE (Polpitiya et
      al., 2008)) (http://omics.pnl.gov/software/), as well as in standalone software
      available at SourceForge (http://sourceforge.net).

PMID- 19602525
TI  - PIQA: pipeline for Illumina G1 genome analyzer data quality assessment.
AB  - SUMMARY: PIQA is a quality analysis pipeline designed to examine genomic reads
      produced by Next Generation Sequencing technology (Illumina G1 Genome Analyzer).
      A short statistical summary, as well as tile-by-tile and cycle-by-cycle graphical
      representation of clusters density, quality scores and nucleotide frequencies
      allow easy identification of various technical problems including defective
      tiles, mistakes in sample/library preparations and abnormalities in the
      frequencies of appearance of sequenced genomic reads. PIQA is written in the R
      statistical programming language and is compatible with bustard, fastq and scarf
      Illumina G1 Genome Analyzer data formats. AVAILABILITY: The PIQA pipeline,
      installation instructions and examples are available at the supplementary web
      site (http://bioinfo.uh.edu/PIQA).

PMID- 19602526
TI  - WebArrayDB: cross-platform microarray data analysis and public data repository.
AB  - MOTIVATION: Cross-platform microarray analysis is an increasingly important
      research tool, but researchers still lack open source tools for storing,
      integrating and analyzing large amounts of microarray data obtained from
      different array platforms. RESULTS: An open source integrated microarray database
      and analysis suite, WebArrayDB (http://www.webarraydb.org), has been developed
      that features convenient uploading of data for storage in a MIAME (Minimal
      Information about a Microarray Experiment) compliant fashion, and allows data to
      be mined with a large variety of R-based tools, including data analysis across
      multiple platforms. Different methods for probe alignment, normalization and
      statistical analysis are included to account for systematic bias. Student's t
      test, moderated t-tests, non-parametric tests and analysis of variance or
      covariance (ANOVA/ANCOVA) are among the choices of algorithms for differential
      analysis of data. Users also have the flexibility to define new factors and
      create new analysis models to fit complex experimental designs. All data can be
      queried or browsed through a web browser. The computations can be performed in
      parallel on symmetric multiprocessing (SMP) systems or Linux clusters.
      AVAILABILITY: The software package is available for the use on a public web
      server (http://www.webarraydb.org) or can be downloaded. are available at
      Bioinformatics online.

PMID- 19602528
TI  - Expertomica metabolite profiling: getting more information from LC-MS using the
      stochastic systems approach.
AB  - Mass spectrometers are sophisticated, fine instruments which are essential in a
      variety applications. However, the data they produce are usually interpreted in a
      rather primitive way, without considering the accuracy of this data and the
      potential errors in identifying peaks. Our new approach corrects this situation
      by dividing the LC-MS output into three components: (i) signature of the analyte,
      (ii) random noise and (iii) systemic noise. The systemic noise is related to the
      instrument and to the particular experiment; its characteristics change in time
      and depend on the analyzed substance. Working with these components allows us to
      quantify the probability of peak errors and, at the same time, to retrieve some
      peaks which get lost in the noise when using the existing methods. Our software
      tool, Expertomica metabolite profiling, automatically evaluates the given
      instrument, detects compounds and calculates the probability of individual peaks.
      It does not need any artificial user-defined parameters or thresholds.
      AVAILABILITY: MATLAB scripts with a simple graphical user interface are free to
      download from http://sourceforge.net/projects/expertomica-eda/. The software
      reads data exported by most Thermo and Agilent spectrometers, and it can also
      read the more general JCAMP-DX ASCII format. Other formats will be supported on
      request, assuming that the user can provide representative data samples.

PMID- 19602527
TI  - A multi-dimensional evidence-based candidate gene prioritization approach for
      complex diseases-schizophrenia as a case.
AB  - MOTIVATION: During the past decade, we have seen an exponential growth of vast
      amounts of genetic data generated for complex disease studies. Currently, across
      a variety of complex biological problems, there is a strong trend towards the
      integration of data from multiple sources. So far, candidate gene prioritization
      approaches have been designed for specific purposes, by utilizing only some of
      the available sources of genetic studies, or by using a simple weight scheme.
      Specifically to psychiatric disorders, there has been no prioritization approach
      that fully utilizes all major sources of experimental data. RESULTS: Here we
      present a multi-dimensional evidence-based candidate gene prioritization approach
      for complex diseases and demonstrate it in schizophrenia. In this approach, we
      first collect and curate genetic studies for schizophrenia from four major
      categories: association studies, linkage analyses, gene expression and literature
      search. Genes in these data sets are initially scored by category-specific
      scoring methods. Then, an optimal weight matrix is searched by a two-step
      procedure (core genes and unbiased P-values in independent genome-wide
      association studies). Finally, genes are prioritized by their combined scores
      using the optimal weight matrix. Our evaluation suggests this approach generates
      prioritized candidate genes that are promising for further analysis or
      replication. The approach can be applied to other complex diseases. AVAILABILITY:
      The collected data, prioritized candidate genes, and gene prioritization tools
      are freely available at http://bioinfo.mc.vanderbilt.edu/SZGR/.

PMID- 19602529
TI  - ADAN: a database for prediction of protein-protein interaction of modular domains
      mediated by linear motifs.
AB  - MOTIVATION: Most of the structures and functions of proteome globular domains are
      yet unknown. We can use high-resolution structures from different modular domains
      in combination with automatic protein design algorithms to predict genome-wide
      potential interactions of a protein. ADAN database and related web tools are
      online resources for the predictive analysis of ligand-domain complexes. ADAN
      database is a collection of different modular protein domains (SH2, SH3, PDZ, WW,
      etc.). It contains 3505 entries with extensive structural and functional
      information available, manually integrated, curated and annotated with cross
      references to other databases, biochemical and thermodynamical data, simplified
      coordinate files, sequence files and alignments. Prediadan, a subset of ADAN
      database, offers position-specific scoring matrices for protein-protein
      interactions, calculated by FoldX, and predictions of optimum ligands and
      putative binding partners. Users can also scan a query sequence against selected
      matrices, or improve a ligand-domain interaction. AVAILABILITY: ADAN is
      accessible at http://adan-embl.ibmc.umh.es/ or http://adan.crg.es/.

PMID- 19602530
TI  - Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or
      in combination with a proton pump inhibitor for people with osteoarthritis.
AB  - OBJECTIVES: To investigate the cost effectiveness of cyclo-oxygenase-2 (COX 2)
      selective inhibitors and traditional non-steroidal anti-inflammatory drugs
      (NSAIDs), and the addition of proton pump inhibitors to these treatments, for
      people with osteoarthritis. DESIGN: An economic evaluation using a Markov model
      and data from a systematic review was conducted. Estimates of cardiovascular and
      gastrointestinal adverse events were based on data from three large randomised
      controlled trials, and observational data were used for sensitivity analyses.
      Efficacy benefits from treatment were estimated from a meta-analysis of trials
      reporting total Western Ontario and McMaster Universities (WOMAC) osteoarthritis
      index score. Other model inputs were obtained from the relevant literature. The
      model was run for a hypothetical population of people with osteoarthritis.
      Subgroup analyses were conducted for people at high risk of gastrointestinal or
      cardiovascular adverse events. Comparators Licensed COX 2 selective inhibitors
      (celecoxib and etoricoxib) and traditional NSAIDs (diclofenac, ibuprofen, and
      naproxen) for which suitable data were available were compared. Paracetamol was
      also included, as was the possibility of adding a proton pump inhibitor
      (omeprazole) to each treatment. MAIN OUTCOME MEASURES: The main outcome measure
      was cost effectiveness, which was based on quality adjusted life years gained.
      Quality adjusted life year scores were calculated from pooled estimates of
      efficacy and major adverse events (that is, dyspepsia; symptomatic ulcer;
      complicated gastrointestinal perforation, ulcer, or bleed; myocardial infarction;
      stroke; and heart failure). RESULTS: Addition of a proton pump inhibitor to both
      COX 2 selective inhibitors and traditional NSAIDs was highly cost effective for
      all patient groups considered (incremental cost effectiveness ratio less than
      pound1000 (euro1175, $1650)). This finding was robust across a wide range of
      effectiveness estimates if the cheapest proton pump inhibitor was used. In our
      base case analysis, adding a proton pump inhibitor to a COX 2 selective inhibitor
      (used at the lowest licensed dose) was a cost effective option, even for patients
      at low risk of gastrointestinal adverse events (incremental cost effectiveness
      ratio approximately pound10 000). Uncertainties around relative adverse event
      rates meant relative cost effectiveness for individual COX 2 selective inhibitors
      and traditional NSAIDs was difficult to determine. CONCLUSIONS: Prescribing a
      proton pump inhibitor for people with osteoarthritis who are taking a traditional
      NSAID or COX 2 selective inhibitor is cost effective. The cost effectiveness
      analysis was sensitive to adverse event data and the specific choice of COX 2
      selective inhibitor or NSAID agent should, therefore, take into account
      individual cardiovascular and gastrointestinal risks.

PMID- 19602536
TI  - Differences in baseline lymphocyte counts and autoreactivity are associated with
      differences in outcome of islet cell transplantation in type 1 diabetic patients.
AB  - OBJECTIVE: The metabolic outcome of islet cell transplants in type 1 diabetic
      patients is variable. This retrospective analysis examines whether differences in
      recipient characteristics at the time of transplantation are correlated with
      inadequate graft function. RESEARCH DESIGN AND METHODS: Thirty nonuremic C
      peptide-negative type 1 diabetic patients had received an intraportal islet cell
      graft of comparable size under an ATG-tacrolimus-mycophenolate mofetil regimen.
      Baseline patient characteristics were compared with outcome parameters during the
      first 6 posttransplant months (i.e., plasma C-peptide, glycemic variability, and
      gain of insulin independence). Correlations in univariate analysis were further
      examined in a multivariate model. RESULTS: Patients that did not become insulin
      independent exhibited significantly higher counts of B-cells as well as a T-cell
      autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD. In one
      of them, a liver biopsy during posttransplant year 2 showed B-cell accumulations
      near insulin-positive beta-cell aggregates. Higher baseline total lymphocytes and
      T-cell autoreactivity were also correlated with lower plasma C-peptide levels and
      higher glycemic variability. CONCLUSIONS: Higher total and B-cell counts and
      presence of T-cell autoreactivity at baseline are independently associated with
      lower graft function in type 1 diabetic patients receiving intraportal islet
      cells under ATG-tacrolimus-mycophenolate mofetil therapy. Prospective studies are
      needed to assess whether control of these characteristics can help increase the
      function of islet cell grafts during the first year posttransplantation.

PMID- 19602537
TI  - Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice.
AB  - OBJECTIVE: Oxyntomodulin (OXM) is a glucagon-like peptide 1 (GLP-1) receptor
      (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in
      obese subjects through increased energy expenditure and decreased energy intake.
      The metabolic effects of OXM have been attributed primarily to GLP1R agonism. We
      examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic
      effects in diet-induced obese mice that are distinct from those obtained with a
      GLP1R-selective agonist. RESEARCH DESIGN AND METHODS: We developed a protease
      resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective
      agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The
      metabolic effects of these two peptides with respect to weight loss, caloric
      reduction, glucose control, and lipid lowering, were compared upon chronic dosing
      in diet-induced obese (DIO) mice. Acute studies in DIO mice revealed metabolic
      pathways that were modulated independent of weight loss. Studies in Glp1r(-/-)
      and Gcgr(-/-) mice enabled delineation of the contribution of GLP1R versus GCGR
      activation to the pharmacology of DualAG. RESULTS: Peptide DualAG exhibits
      superior weight loss, lipid-lowering activity, and antihyperglycemic efficacy
      comparable to GLPAG. Improvements in plasma metabolic parameters including
      insulin, leptin, and adiponectin were more pronounced upon chronic treatment with
      DualAG than with GLPAG. Dual receptor agonism also increased fatty acid oxidation
      and reduced hepatic steatosis in DIO mice. The antiobesity effects of DualAG
      require activation of both GLP1R and GCGR. CONCLUSIONS: Sustained GLP1R/GCGR dual
      agonism reverses obesity in DIO mice and is a novel therapeutic approach to the
      treatment of obesity.

PMID- 19602538
TI  - Adipose tissue plasticity during catch-up fat driven by thrifty metabolism:
      relevance for muscle-adipose glucose redistribution during catch-up growth.
AB  - OBJECTIVE: Catch-up growth, a risk factor for later type 2 diabetes, is
      characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat),
      and enhanced glucose utilization in adipose tissue. Our objective was to
      characterize the determinants of enhanced glucose utilization in adipose tissue
      during catch-up fat. RESEARCH DESIGN AND METHODS: White adipose tissue
      morphometry, lipogenic capacity, fatty acid composition, insulin signaling, in
      vivo glucose homeostasis, and insulinemic response to glucose were assessed in a
      rat model of semistarvation-refeeding. This model is characterized by glucose
      redistribution from skeletal muscle to adipose tissue during catch-up fat that
      results solely from suppressed thermogenesis (i.e., without hyperphagia).
      RESULTS: Adipose tissue recovery during the dynamic phase of catch-up fat is
      accompanied by increased adipocyte number with smaller diameter, increased
      expression of genes for adipogenesis and de novo lipogenesis, increased fatty
      acid synthase activity, increased proportion of saturated fatty acids in
      triglyceride (storage) fraction but not in phospholipid (membrane) fraction, and
      no impairment in insulin signaling. Furthermore, it is shown that
      hyperinsulinemia and enhanced adipose tissue de novo lipogenesis occur
      concomitantly and are very early events in catch-up fat. CONCLUSIONS: These
      findings suggest that increased adipose tissue insulin stimulation and
      consequential increase in intracellular glucose flux play an important role in
      initiating catch-up fat. Once activated, the machinery for lipogenesis and
      adipogenesis contribute to sustain an increased insulin-stimulated glucose flux
      toward fat storage. Such adipose tissue plasticity could play an active role in
      the thrifty metabolism that underlies glucose redistribution from skeletal muscle
      to adipose tissue.

PMID- 19602539
TI  - Effectiveness of a pragmatic education program designed to promote walking
      activity in individuals with impaired glucose tolerance: a randomized controlled
      trial.
AB  - OBJECTIVE To investigate whether a pragmatic structured education program with
      and without pedometer use is effective for promoting physical activity and
      improving glucose tolerance in those with impaired glucose tolerance (IGT).
      RESEARCH DESIGN AND METHODS Overweight and obese individuals with IGT were
      recruited from ongoing screening studies at the University Hospitals of
      Leicester, U.K. Participants were randomly assigned to one of three groups. Group
      1 received a 3-h group-based structured education program designed to promote
      walking activity using personalized steps-per-day goals and pedometers. Group 2
      received a 3-h group-based structured education program designed to promote
      walking activity using generic time-based goals. Group 3 received a brief
      information leaflet (control condition). Outcomes included an oral glucose
      tolerance test, standard anthropometric measures, ambulatory activity, and
      psychological variables. Follow-up was conducted at 3, 6, and 12 months. RESULTS
      A total of 87 individuals (66% male, mean age 65 years) were included in this
      study. At 12 months, significant decreases in 2-h postchallenge glucose and
      fasting glucose of -1.31 mmol/l (95% CI -2.20 to -0.43) and -0.32 mmol/l (-0.59
      to -0.03), respectively, were seen in the pedometer group compared with the
      control group. No significant improvements in glucose control were seen in those
      given the standard education program. CONCLUSIONS This study suggests that a
      pragmatic structured education program that incorporates pedometer use is
      effective for improving glucose tolerance in those with IGT. This result is
      likely to have important implications for future primary care-based diabetes
      prevention initiatives.

PMID- 19602540
TI  - A phylogenetic mixture model for the evolution of gene expression.
AB  - Microarray platforms are used increasingly to make comparative inferences through
      genome-wide surveys of gene expression. Although recent studies focus on
      describing the evidence for natural selection using estimates of the within- and
      between-taxa mutational variances, these methods do not explicitly or flexibly
      account for predicted nonindependence due to phylogenetic associations between
      measurements. In the interest of parsing the effects of selection: we introduce a
      mixture model for the comparative analysis of variation in gene expression across
      multiple taxa. This class of models isolates the phylogenetic signal from the
      nonphylogenetic and the heritable signal from the nonheritable while measuring
      the proper amount of correction. As a result, the mixture model resolves
      outstanding differences between existing models, relates different ways to
      estimate the across taxa variance, and induces a likelihood ratio test for
      selection. We investigate by simulation and application the feasibility and
      utility of estimation of the required parameters and the power of the proposed
      test. We illustrate analysis under this mixture model with a gene duplication
      family data set.

PMID- 19602542
TI  - Bilaterian phylogeny: a broad sampling of 13 nuclear genes provides a new
      Lophotrochozoa phylogeny and supports a paraphyletic basal acoelomorpha.
AB  - During the past decade, great progress has been made in clarifying the
      relationships among bilaterian animals. Studies based on a limited number of
      markers established new hypotheses such as the existence of three superclades
      (Deuterostomia, Ecdysozoa, and Lophotrochozoa) but left major questions
      unresolved. The data sets used to the present either bear few characters for many
      taxa (i.e., the ribosomal genes) or present many characters but lack many phyla
      (such as recent phylogenomic approaches) failing to provide definitive answers
      for all the regions of the bilaterian tree. We performed phylogenetic analyses
      using a molecular matrix with a high number of characters and bilaterian phyla.
      This data set is built from 13 genes (8,880 bp) belonging to 90 taxa from 27
      bilaterian phyla. Probabilistic analyses robustly support the three superclades,
      the monophyly of Chordata, a spiralian clade including Brachiozoa, the basal
      position of a paraphyletic Acoelomorpha, and point to an ecdysozoan affiliation
      for Chaetognatha. This new phylogeny not only agrees with most classical
      molecular results but also provides new insights into the relationships between
      lophotrochozoans and challenges the results obtained using high-throughput
      strategies, highlighting the problems associated with the current trend to
      increase gene number rather than taxa.

PMID- 19602541
TI  - The unique Morgue ubiquitination protein is conserved in a diverse but restricted
      set of invertebrates.
AB  - Drosophila Morgue is a unique ubiquitination protein that facilitates programmed
      cell death and associates with DIAP1, a critical cell death inhibitor with E3
      ubiquitin ligase activity. Morgue possesses a unique combination of functional
      domains typically associated with distinct types of ubiquitination enzymes. This
      includes an F box characteristic of the substrate-binding subunit in Skp, Cullin,
      and F box (SCF)-type ubiquitin E3 ligase complexes and a variant ubiquitin E2
      conjugase domain where the active site cysteine is replaced by a glycine. Morgue
      also contains a single C4-type zinc finger motif. This architecture suggests
      potentially novel ubiquitination activities for Morgue. In this study, we address
      the evolutionary origins of this distinctive protein utilizing a combination of
      bioinformatics and molecular biology approaches. We find that Morgue exhibits
      widespread but restricted phylogenetic distribution among metazoans. Morgue
      proteins were identified in a wide range of Protostome phyla, including
      Arthropoda, Annelida, Mollusca, Nematoda, and Platyhelminthes. However, with one
      potential exception, Morgue was not detected in Deuterostomes, including
      Chordates, Hemichordates, or Echinoderms. Morgue was also not found in
      Ctenophora, Cnidaria, Placozoa, or Porifera. Characterization of Morgue sequences
      within specific animal lineages suggests that gene deletion or acquisition has
      occurred during divergence of nematodes and that at least one arachnid expresses
      an atypical form of Morgue consisting only of the variant E2 conjugase domain.
      Analysis of the organization of several morgue genes suggests that exon-shuffling
      events have contributed to the evolution of the Morgue protein. These results
      suggest that Morgue mediates conserved and distinctive ubiquitination functions
      in specific cell death pathways.

PMID- 19602543
TI  - Temporal constraints on the incorporation of regulatory mutants in evolutionary
      pathways.
AB  - Understanding the molecular details of the sequence of events in multistep
      evolutionary pathways can reveal the extent to which natural selection exploits
      regulatory mutations affecting expression, amino acid replacements affecting the
      active site, amino acid replacements affecting protein folding or stability, or
      variations affecting gene copy number. In experimentally exploring the adaptive
      landscape of the evolution of resistance to beta-lactam antibiotics in enteric
      bacteria, we noted that a regulatory mutation that increases beta-lactamase
      expression by about 2-fold has a very strong tendency to be fixed at or near the
      end of the evolutionary pathway. This pattern contrasts with previous experiments
      selecting for the utilization of novel substrates, in which regulatory mutations
      that increase expression are often fixed early in the process. To understand the
      basis of the difference, we carried out experiments in which the expression of
      beta-lactamase was under the control of a tunable arabinose promoter. We find
      that the fitness effect of an increase in gene expression is highly dependent on
      the catalytic activity of the coding sequence. An increase in expression of an
      inefficient enzyme has a negligible effect on drug resistance; however, the
      effect of an increase in expression of an efficient enzyme is very large. The
      contrast in the temporal incorporation of regulatory mutants between antibiotic
      resistance and the utilization of novel substrates is related to the nature of
      the function that relates enzyme activity to fitness. A mathematical model of
      beta-lactam resistance is examined in detail and shown to be consistent with the
      observed results.

PMID- 19602544
TI  - Overexpression of the soybean GmERF3 gene, an AP2/ERF type transcription factor
      for increased tolerances to salt, drought, and diseases in transgenic tobacco.
AB  - A new member of the AP2/ERF transcription factor family, GmERF3, was isolated
      from soybean. Sequence analysis showed that GmERF3 contained an AP2/ERF domain of
      58 amino acids and two putative nuclear localization signal (NLS) domains. It
      belonged to a group IV protein in the ERF (ethylene response factor) subfamily as
      typified by a conserved N-terminal motif [MCGGAI(I/L)]. Expression of GmERF3 was
      induced by treatments with high salinity, drought, abscisic acid (ABA), salicylic
      acid (SA), jasmonic acid (JA), ethylene (ET), and soybean mosaic virus (SMV),
      whereas there was no significant GmERF3 mRNA accumulation under cold stress
      treatment. GmERF3 could bind to the GCC box and DRE/CRT element, and was targeted
      to the nucleus when transiently expressed in onion epidermal cells. The GmERF3
      protein fused to the GAL4 DNA-binding domain to activate transcription of
      reporter genes in yeast. Ectopic expression of the GmERF3 gene in transgenic
      tobacco plants induced the expression of some PR genes and enhanced resistance
      against infection by Ralstonia solanacearum, Alternaria alternata, and tobacco
      mosaic virus (TMV), and gave tolerance to high salinity and dehydration stresses.
      Furthermore, overexpression of GmERF3 in transgenic tobacco led to higher levels
      of free proline and soluble carbohydrates compared to wild-type plants under
      drought conditions. The overall results suggested that GmERF3 as an AP2/ERF
      transcription factor may play dual roles in response to biotic and abiotic
      stresses in plants.

PMID- 19602545
TI  - Assimilation of xylem-transported 13C-labelled CO2 in leaves and branches of
      sycamore (Platanus occidentalis L.).
AB  - Previous reports have shown that CO(2) dissolved in xylem sap in tree stems can
      move upward in the transpiration stream. To determine the fate of this dissolved
      CO(2), the internal transport of respired CO(2) at high concentration from the
      bole of the tree was simulated by allowing detached young branches of sycamore
      (Platanus occidentalis L.) to transpire water enriched with a known quantity of
      (13)CO(2) in sunlight. Simultaneously, leaf net photosynthesis and CO(2) efflux
      from woody tissue were measured. Branch and leaf tissues were subsequently
      analysed for (13)C content to determine the quantity of transported (13)CO(2)
      label that was fixed. Treatment branches assimilated an average of 35% (SE=2.4)
      of the (13)CO(2) label taken up in the treatment water. The majority was fixed in
      the woody tissue of the branches, with smaller amounts fixed in the leaves and
      petioles. Overall, the fixation of internally transported (13)CO(2) label by
      woody tissues averaged 6% of the assimilation of CO(2) from the atmosphere by the
      leaves. Woody tissue assimilation rates calculated from measurements of (13)C
      differed from rates calculated from measurements of CO(2) efflux in the lower
      branch but not in the upper branch. The results of this study showed
      unequivocally that CO(2) transported in xylem sap can be fixed in photosynthetic
      cells in the leaves and branches of sycamore trees and provided evidence that
      recycling of xylem-transported CO(2) may be an important means by which trees
      reduce the carbon cost of respiration.

PMID- 19602546
TI  - Prediction of muscle-invasive bladder cancer using urinary proteomics.
AB  - PURPOSE: Minimally invasive methods of predicting the risk of muscle-invasive
      urothelial bladder carcinoma may expedite appropriate therapy and reduce
      morbidity and cost. EXPERIMENTAL DESIGN: Here, capillary electrophoresis coupled
      mass spectrometry was used to identify urinary polypeptide bladder cancer
      biomarkers in 127 patients. These markers were used to construct a panel
      discriminating muscle-invasive from noninvasive disease, which was refined in 297
      additional samples from healthy volunteers, patients with malignant and
      nonmalignant genitourinary conditions. Sequencing of panel polypeptides was then
      done. Finally, the ability of the panel to predict muscle-invasive disease was
      evaluated prospectively in 130 bladder carcinoma patients. Four sequenced
      polypeptides formed a panel predictive of muscle-invasive disease. RESULTS:
      Prospective evaluation of this panel revealed a sensitivity of 81% [95%
      confidence interval (CI), 69-90] and specificity of 57% (95% CI, 45-69) for
      muscle-invasive disease. Multivariate analysis revealed the panel (P < 0.0001)
      and tumor grade (P = 0.0001), but not urine cytology, predict muscle invasion. A
      model including grade and panel polypeptide levels improved sensitivity [92% (95%
      CI, 82-97)] and specificity [68% (95% CI, 55-79)] for muscle-invasive disease. A
      model score of >0.88 provided a negative predictive value of 77% and positive
      predictive value of 90% for muscle invasion. CONCLUSIONS: Use of urinary peptides
      seems promising in estimating the probability a patient harbors muscle-invasive
      urothelial bladder cancer. These peptides may also shed novel insights into the
      biology of bladder tumor progression not obtainable by other methods. Clinical
      trials seem warranted to evaluate the effect of this approach on practice.

PMID- 19602547
TI  - Autologous melanoma vaccine induces antitumor and self-reactive immune responses
      that affect patient survival and depend on MHC class II expression on vaccine
      cells.
AB  - PURPOSE: Autologous melanoma cells display a broad variety of tumor antigens and
      were used for treatment of American Joint Committee on Cancer stages III and IV
      melanoma as an adjuvant or active therapy. Survival data and immune response were
      evaluated in vaccinated patients. EXPERIMENTAL DESIGN: Forty-seven patients
      received 2,4-dinitrophenyl-conjugated autologous melanoma vaccine as an adjuvant
      (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood
      sampled before vaccination and after five or eight vaccine doses was evaluated
      against melanoma cells and autologous peripheral blood mononuclear cells using
      IFNgamma enzyme-linked immunospot. Serum levels of antilivin, an inhibitor of
      apoptosis, and anti-gp100 IgG were determined. RESULTS: The immunologic effect of
      the vaccine differed between the two groups of patients. In the adjuvant group,
      there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035)
      after vaccination and an increase in antimelanoma CD4 T cells correlating with
      improved overall survival (P = 0.04). In the therapeutic group, there was no
      objective tumor regression; antimelanoma T-cell reactivity increased by a small
      amount, stayed the same, or in some cases decreased. In all patients, a
      significant increase was noted in CD4 T-cell reactivity against autologous
      peripheral blood mononuclear cells (P = 0.02), which did not affect survival.
      Increased antilivin IgG was associated with improved survival. Expression of MHC
      class II on melanoma cells was vital for the immunogenicity of the vaccine.
      CONCLUSION: Autologous melanoma cell vaccine is capable of inducing effective
      antimelanoma CD4 T-cell activity associated with improved survival. Patients with
      active metastatic disease generally displayed reduced immune response and gained
      little from active immunization.

PMID- 19602548
TI  - Functional unresponsiveness and replicative senescence of myeloid leukemia
      antigen-specific CD8+ T cells after allogeneic stem cell transplantation.
AB  - PURPOSE: The therapeutic effect of allogeneic hematopoietic stem cell
      transplantation (HSCT) for patients with myeloid malignancies has been attributed
      in part to a graft-versus-leukemia effect that is dependent on donor T
      lymphocytes. CD8(+) T-cell responses to MHC class I-restricted tumor epitopes,
      not just allogeneic antigens, may help mediate antileukemia effects after HSCT,
      but the specificity and function of such cells are not completely understood.
      EXPERIMENTAL DESIGN: We examined the diversity, phenotype, and functional
      potential of leukemia-associated antigen-specific CD8(+) T cells in patients with
      myeloid leukemia following allogeneic HSCT. Screening for antigen-specific T
      cells was accomplished with a peptide/MHC tetramer library. RESULTS: Patients
      with acute myelogenous leukemia or chronic myelogenous leukemia in remission
      following HSCT exhibited significant numbers of peripheral blood CD8(+) T cells
      that recognized varying combinations of epitopes derived from leukemia-associated
      antigens. However, these cells failed to proliferate, release cytokines, or
      degranulate in response to antigen-specific stimuli. As early as 2 months after
      HSCT, CD8(+) T cells from patients were predominantly CD28(-) CD57(+) and had
      relatively short telomeres, consistent with cellular senescence. CONCLUSIONS:
      Circulating leukemia-specific CD8(+) T cells are prominent in myeloid leukemia
      patients after HSCT, but such cells are largely functionally unresponsive, most
      likely due to replicative senescence. These findings carry important implications
      for the understanding of the graft-versus-leukemia effect and for the rational
      design of immunotherapeutic strategies for patients with myeloid leukemias.

PMID- 19602549
TI  - The role of nucleoside transporters in the erythrocyte disposition and oral
      absorption of ribavirin in the wild-type and equilibrative nucleoside transporter
      1-/- mice.
AB  - Ribavirin [1-(beta-d-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide] is the
      treatment of choice for hepatitis C virus infection. Ribavirin is a substrate of
      several nucleoside transporters, including the equilibrative nucleoside
      transporter (Ent) and the concentrative nucleoside transporter 2. To determine
      the role of Ent1 in ribavirin absorption and erythrocyte distribution, we
      examined its pharmacokinetics in Ent1-null mice. After intravenous
      administration, we found that the erythrocyte area under the curve (AUC(0-12 h))
      was reduced 3.05-fold along with 2.63-fold reduction of erythrocyte versus plasma
      AUC ratio in the Ent1(-/-) mice, whereas there was no significant difference in
      the plasma AUC(0-12 h) between Ent1(+/+) and Ent1(-/-) mice. After 48 h, we found
      a similar fraction of ribavirin or total radioactivity excreted in the urine
      between the Ent1(+/+) and Ent1(-/-) mice. After oral administration of three
      different doses, 0.024, 0.24, and 6.1 mg/kg, we found that the dose-normalized
      plasma AUC(0-12 h) of ribavirin was 69.7 +/- 12.0, 20.7 +/- 1.5, and 18.3 +/- 2.7
      min/l, respectively, in the Ent1(+/+) mice and 18.9 +/- 2.8, 13.0 +/- 0.5, and
      12.2 +/- 1.0 min/l, respectively, in the Ent1(-/-) mice. It is interesting that
      at the highest dose, the dose-normalized plasma AUC(0-30 min), AUC(0-12 h), and
      C(max) in the Ent1(+/+) mice were decreased 4.0-, 3.8-, and 3.4-fold,
      respectively, compared with the lowest dose, suggesting absorption was saturated
      at the highest dose we used. The dose-normalized plasma AUC(0-12 h) was 3.7- and
      1.5-fold lower at the lowest and the highest dose, respectively, in the Ent1(-/-)
      mice compared with those of the Ent1(+/+) mice. Our findings indicate that Ent1
      plays a significant role in the oral absorption and erythrocyte distribution of
      ribavirin.

PMID- 19602550
TI  - Molecular pharmacology of the amiloride analog 3-amino-6-chloro-5-[(4-chloro
      benzyl)amino]-n-[[(2,4-dimethylbenzyl)-amino]iminomethyl]-pyrazinecarboxamide (CB
      DMB) as a pan inhibitor of the Na+-Ca2+ exchanger isoforms NCX1, NCX2, and NCX3
      in stably transfected cells.
AB  - With the help of single-cell microflorimetry, (45)Ca(2+) radiotracer fluxes, and
      patch-clamp in whole-cell configuration, we examined the effect of the amiloride
      derivative 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-N-[[(2,4
      dimethylbenzyl)amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) on the activity of
      the three isoforms of the Na(+)/Ca(2+) exchanger (NCX) and on several other
      membrane currents including voltage- and pH-sensitive ones. This amiloride analog
      suppressed the bidirectional activity of all NCX isoforms in a concentration
      dependent manner. The IC(50) values of CB-DMB were in the nanomolar range for the
      outward and the inward components of the bidirectional NCX1, NCX2, and NCX3
      activity. Deletion mutagenesis showed that CB-DMB inhibited NCX activity mainly
      at level of the f-loop but not through the interaction with Gly833 located at the
      level of the alpha(2) repeat. On the other hand, CB-DMB suppressed in the
      micromolar range the other plasma membrane currents encoded by voltage-dependent
      Ca(2+) channels, tetrodotoxin-sensitive Na(+) channels, and pH-sensitive ASIC1a.
      Collectively, the data of the present study showed that CB-DMB, when used in the
      nanomolar range, is one of the most potent compounds that can block the activity
      of the three NCX isoforms when they work both in the forward and in the reverse
      modes of operation without interfering with other ionic channels.

PMID- 19602551
TI  - Differential activation of guinea pig intrinsic cardiac neurons by the PAC1
      agonists maxadilan and pituitary adenylate cyclase-activating polypeptide 27
      (PACAP27).
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) evokes tachycardia
      followed by a larger cholinergic bradycardia in isolated guinea pig hearts. We
      used the selective PAC1 receptor agonist maxadilan and vasoactive intestinal
      polypeptide (VIP) to test the hypothesis that PACAP27-evoked tachycardia and
      bradycardia are mediated by VPAC and PAC1 receptors, respectively. Chronotropic
      actions of these peptides were evaluated in isolated perfused hearts. Direct
      neuronal actions were determined by intracellular voltage recordings from
      cholinergic neurons in atrial ganglion whole mounts. Administration of 1 nmol of
      PACAP27 to isolated hearts evoked typical biphasic rate responses, whereas 1 nmol
      of maxadilan caused only a minor rate decrease. Desensitization with VIP
      eliminated the positive chronotropic effect of PACAP27 selectively. Local
      application of PACAP27 to cardiac neurons frequently evoked slow depolarization
      and caused prolonged increase of neuronal excitability. Maxadilan rarely affected
      membrane potential but consistently increased excitability. VIP had no effect on
      excitability and evoked depolarization in only a few neurons. Because maxadilan
      increased neuronal excitability but did not trigger action potentials as PACAP
      often does, we evaluated the interaction of maxadilan with substance P (SP) in
      isolated hearts. SP depolarizes cardiac neurons more consistently than PACAP,
      often triggers neuronal action potentials, and causes bradycardia but does not
      increase neuronal excitability. Maxadilan had a persistent effect to augment
      negative chronotropic responses to SP. These findings support our hypothesis that
      PACAP evokes tachycardia and bradycardia through VPAC and PAC1 receptors,
      respectively. They also suggest that maxadilan and PACAP27 differ in activating
      PAC1 receptors on cardiac neurons and/or stimulating downstream signaling
      mechanisms.

PMID- 19602552
TI  - Lack of cocaine self-administration in mice expressing a cocaine-insensitive
      dopamine transporter.
AB  - Cocaine addiction is a worldwide public health problem for which there are no
      established treatments. The dopamine transporter (DAT) is suspected as the
      primary target mediating cocaine's abuse-related effects based on numerous
      pharmacological studies. However, in a previous study, DAT knockout mice were
      reported to self-administer cocaine, generating much debate regarding the
      importance of the DAT in cocaine's abuse-related effects. Here, we show that mice
      expressing a "knockin" of a cocaine-insensitive but functional DAT did not self
      administer cocaine intravenously despite normal food-maintained responding and
      normal intravenous self-administration of amphetamine and a direct dopamine
      agonist. Our results have three implications. First, they imply a crucial role
      for high-affinity DAT binding of cocaine in mediating its reinforcing effects,
      reconciling mouse genetic engineering approaches with data from classic
      pharmacological studies. Second, they demonstrate the usefulness of knockin
      strategies that modify specific amino acid sequences within a protein. Third,
      they show that it is possible to alter the DAT protein sequence in such a way as
      to selectively target its interaction with cocaine, while sparing other behaviors
      dependent on DAT function. Thus, molecular engineering technology could advance
      the development of highly specialized compounds such as a dopamine-sparing
      "cocaine antagonist."

PMID- 19602553
TI  - Novel environment and GABA agonists alter event-related potentials in N-methyl-D
      aspartate NR1 hypomorphic and wild-type mice.
AB  - Clinical and experimental data suggest dysregulation of N-methyl-d-aspartate
      receptor (NMDAR)-mediated glutamatergic pathways in schizophrenia. The
      interaction between NMDAR-mediated abnormalities and the response to novel
      environment has not been studied. Mice expressing 5 to 10% of normal N-methyl-d
      aspartate receptor subunit 1 (NR1) subunits [NR1(neo)(-/-)] were compared with
      wild-type littermates for positive deflection at 20 ms (P20) and negative
      deflection at 40 ms (N40) auditory event-related potentials (ERPs). Groups were
      tested for habituation within and across five testing sessions, with novel
      environment tested during a sixth session. Subsequently, we examined the effects
      of a GABA(A) positive allosteric modulator (chlordiazepoxide) and a GABA(B)
      receptor agonist (baclofen) as potential interventions to normalize aberrant
      responses. There was a reduction in P20, but not N40 amplitude within each
      habituation day. Although there was no amplitude or gating change across
      habituation days, there was a reduction in P20 and N40 amplitude and gating in
      the novel environment. There was no difference between genotypes for N40. Only
      NR1(neo)(-/-) mice had reduced P20 in the novel environment. Chlordiazepoxide
      increased N40 amplitude in wild-type mice, whereas baclofen increased P20
      amplitude in NR1(neo)(-/-) mice. As noted in previous publications, the pattern
      of ERPs in NR1(neo)(-/-) mice does not recapitulate abnormalities in
      schizophrenia. In addition, reduced NR1 expression does not influence N40
      habituation but does affect P20 in a novel environment. Thus, the pattern of P50
      (positive deflection at 50 ms) but not N100 (negative deflection at 100 ms) in
      human studies may relate to subjects' reactions to unfamiliar environments. In
      addition, NR1 reduction decreased GABA(A) receptor-mediated effects on ERPs while
      causing increased GABA(B) receptor-mediated effects. Future studies will examine
      changes in GABA receptor subunits after reductions in NR1 expression.

PMID- 19602555
TI  - Utility of salivary cortisol measurements in Cushing's syndrome and adrenal
      insufficiency.
AB  - CONTEXT: The measurement of cortisol in saliva is a simple, reproducible, and
      reliable test to evaluate the normal and disordered control of the hypothalamic
      pituitary-adrenal (HPA) axis. There are a variety of simple methods to obtain
      saliva samples without stress, making this a robust test applicable to many
      different experimental and clinical situations. EVIDENCE ACQUISITION: Ovid
      Medline and PubMed from 1950 to present were searched using the following
      strategies: [<saliva or salivary>and<cortisol or hydrocortisone>and<Cushing or
      Cushing's>] and [<saliva or salivary>and<cortisol or hydrocortisone>and<adrenal
      insufficiency or hypoadrenalism or hypopituitarism or Addison's disease>]. The
      bibliographies of all relevant citations were evaluated for any additional
      appropriate citations. EVIDENCE SYNTHESIS: Measurement of an elevated late-night
      (2300 to 2400 h) salivary cortisol has a greater than 90% sensitivity and
      specificity for the diagnosis of endogenous Cushing's syndrome. Late-night
      salivary cortisol measurements are also useful to monitor patients for remission
      and/or recurrence after pituitary surgery for Cushing's disease. Because it is a
      surrogate for plasma free cortisol, the measurement of salivary cortisol may be
      useful during an ACTH stimulation test in patients with increased plasma binding
      protein concentrations due to increased estrogen, or decreased plasma binding
      protein concentrations during critical illness. Most reference laboratories now
      offer salivary cortisol testing. CONCLUSIONS: It is expected that the use of the
      measurement of salivary cortisol will become routine in the evaluation of
      patients with disorders of the HPA axis.

PMID- 19602554
TI  - Growth hormone and sex steroid effects on serum glucose, insulin, and lipid
      concentrations in healthy older women and men.
AB  - CONTEXT: With aging, GH, IGF-I, and sex steroid concentrations and glucose
      tolerance decrease, and body fat and serum lipids increase. OBJECTIVE: The aim of
      the study was to assess GH and/or sex steroid administration effects on serum
      glucose, insulin, insulin sensitivity, and lipids in older individuals. DESIGN: A
      double-masked, 2 x 2 factorial, placebo-controlled, double-dummy design was used
      for the study. INTERVENTION: GH and/or sex steroid [transdermal estradiol plus
      oral medroxyprogesterone acetate in women (HRT); testosterone enanthate (T) in
      men] were administered for 6 months. PARTICIPANTS: Healthy, community-dwelling
      women (n = 57) and men (n = 74) ages 65-88 yr (mean, 72 yr) participated in the
      study. MAIN OUTCOME MEASURES: We measured serum glucose, insulin, and insulin
      sensitivity [quantitative insulin sensitivity check index (QUICKI) and insulin
      sensitivity index (ISI)] before and during an oral glucose tolerance test and
      lipid profiles. RESULTS: In women, GH did not alter oral glucose tolerance test
      120 min or 2-h area under the curve (AUC) glucose values, but it increased 120
      min insulin and AUC insulin. There were no significant effects of HRT or GH+HRT.
      ISI and QUICKI decreased after GH. In men, GH increased 120 min and AUC glucose
      and insulin AUC. GH+T increased 120 min glucose and glucose and insulin AUCs. T
      alone did not affect glucose or insulin. ISI decreased after GH and GH+T, whereas
      QUICKI decreased after GH. GH in women and men and GH+T in men decreased QUICKI
      by 4 wk. In women, HRT decreased total cholesterol and low-density lipoprotein
      (LDL)-cholesterol, and GH decreased LDL-cholesterol. In men, total cholesterol
      decreased after T and GH+T. LDL-cholesterol decreased after GH and GH+T. GH
      increased serum triglycerides. CONCLUSIONS: GH administration to healthy older
      individuals for 6 months increased insulin resistance with moderately beneficial
      effects on lipids.

PMID- 19602556
TI  - Association of thyroid gland volume, serum insulin-like growth factor-I, and
      anthropometric variables in euthyroid prepubertal children.
AB  - CONTEXT AND OBJECTIVE: Few studies have focused on the interrelation between
      thyroid size, anthropometric variables, and IGF-I in adults, but such data are
      lacking for children. We have investigated thyroid gland volume and several
      hormonal and anthropometric variables in prepubertal children. DESIGN AND
      PARTICIPANTS: A total of 859 prepubertal euthyroid Danish children aged 4-9 yr
      underwent a thorough clinical investigation, including anthropometrical
      measurements and determination of TSH, thyroid hormones, autoantibodies, urinary
      iodine excretion, and thyroid volume (TV) by ultrasound. Longitudinal growth data
      from birth were available. RESULTS: TV increased significantly with age (r =
      0.487; P < 0.001). Mean TV +/- sd for different age groups were as follows: 4 yr,
      2.2 +/- 1.4 ml; 5 yr, 2.5 +/- 1.3 ml; 6 yr, 2.8 +/- 1.3 ml; 7 yr, 3.2 +/- 1.3 ml;
      8 yr, 3.5 +/- 1.3 ml; 9 yr, 3.7 +/- 1.3 ml. We found a significant positive
      association between IGF-I and TV (P < 0.001). Furthermore, in multiple regression
      analyses, TSH (P < 0.013), free T(4) (P < 0.001), lean body mass (P < 0.001), and
      body surface area (P < 0.001) as well as other anthropometrical measurements were
      identified as factors significantly associated with TV. Family history of thyroid
      disease and presence of incidental abnormal ultrasound findings were also
      positively associated with TV (P = 0.025 and 0.022, respectively). CONCLUSIONS:
      In our cohort of prepubertal Danish children, the GH/IGF-I-axis was positively
      correlated with thyroid size, suggesting a role in the regulation of thyroid
      growth. Moreover, anthropometric measurements, in particular body surface area,
      were the best predictors of TV.

PMID- 19602557
TI  - Prostaglandin E2 as a regulator of germ cells during ovarian development.
AB  - CONTEXT: The formation of primordial follicles occurs during fetal life yet is
      critical to the determination of adult female fertility. Prior to this stage,
      germ cells proliferate, enter meiosis, and associate with somatic cells. Growth
      and survival factors implicated in these processes include activin A (INHBA), the
      neurotrophins BDNF and NT4 (NTF5), and MCL1. The prostaglandins have pleiotrophic
      roles in reproduction, notably in ovulation and implantation, but there are no
      data regarding roles for prostaglandins in human fetal ovarian development.
      OBJECTIVE: The aim of the study was to investigate a possible role for
      prostaglandin (PG) E(2) in human fetal ovary development. DESIGN: In vitro
      analysis of ovarian development between 8 and 20 wk gestation was performed. MAIN
      OUTCOME MEASURE(S): The expression patterns of PG synthesis enzymes and the
      PGE(2) receptors EP2 and EP4 in the ovary were assessed, and downstream effects
      of PGE(2) on gene expression were analyzed. RESULTS: Ovarian germ cells express
      the PG synthetic enzymes COX2 and PTGES as well as the EP2 and EP4 receptors,
      whereas COX1 is expressed by ovarian somatic cells. Treatment in vitro with
      PGE(2) increased the expression of BDNF mRNA 1.7 +/- 0.16-fold (P = 0.004); INHBA
      mRNA, 2.1 +/- 0.51-fold (P = 0.04); and MCL1 mRNA, 1.15 +/- 0.06-fold (P = 0.04),
      but not that of OCT4, DAZL, VASA, NTF5, or SMAD3. CONCLUSIONS: These data
      indicate novel roles for PGE(2) in the regulation of germ cell development in the
      human ovary and show that these effects may be mediated by the regulation of
      factors including BDNF, activin A, and MCL1.

PMID- 19602558
TI  - Clinical and molecular characterization of a novel selenocysteine insertion
      sequence-binding protein 2 (SBP2) gene mutation (R128X).
AB  - CONTEXT: Although acquired abnormalities of thyroid hormone metabolism are
      common, inherited defects in humans involving the synthesis of selenoproteins,
      including iodothyronine deiodinases, have been described in only one recent
      publication. OBJECTIVE: We report the study of a novel selenocysteine insertion
      sequence-binding protein 2 (SBP2) gene mutation (R128X) and its clinical and
      molecular characterization. SUBJECTS AND METHODS: A family of African origin was
      studied. The proband presented with growth retardation, low serum selenium level,
      and thyroid test abnormalities consisting of high serum total and free T(4)
      concentrations associated with low T(3), high rT(3), and normal TSH. The entire
      coding region of the SBP2 gene was sequenced and minigenes constructed to explain
      the nature of the defect. RESULTS: The proband was homozygous for a nonsense gene
      mutation that produces an early stop codon (R128X). Both parents and a sister
      were heterozygous but showed no growth or thyroid test abnormalities. Despite the
      severity of the defect, the patient had a relatively mild phenotype, similar to
      that associated with partial SBP2 deficiency. In vitro analysis showed that the
      mutant minigene synthesized SBP2 from at least three downstream ATGs capable of
      generating molecules containing the essential functional domains. Treatment with
      l-T(3) accelerated the growth velocity and advanced the bone age. CONCLUSIONS: We
      identified a novel SBP2 gene mutation producing an early arrest in the synthesis
      of a full-length molecule. The demonstration that SBP2 isoforms containing all
      functional domains could be synthesized from three downstream ATGs explains the
      relatively mild phenotype caused by this defect.

PMID- 19602559
TI  - Peak growth hormone-releasing hormone-arginine-stimulated growth hormone is
      inversely associated with intramyocellular and intrahepatic lipid content in
      premenopausal women with obesity.
AB  - CONTEXT: Visceral adiposity is a strong determinant of GH secretion, and low
      endogenous GH secretion is associated with increased insulin resistance, a key
      component of the metabolic syndrome. Increased fat accumulation in skeletal
      muscle and liver may play an etiological role in the development of insulin
      resistance and other complications of the metabolic syndrome. Little is known
      about the role of decreased endogenous GH secretion in the pathogenesis of
      insulin resistance in obesity. OBJECTIVE: To investigate the relationship between
      intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in
      premenopausal women with obesity. DESIGN AND SETTING: We conducted a cross
      sectional study at a clinical translational research center. PATIENTS: Patients
      included 21 premenopausal women with obesity (mean body mass index, 34.0 +/- 4.5
      kg/m(2)) and 17 normal-weight controls (mean body mass index, 21.9 +/- 2.0
      kg/m(2)) of comparable mean age. MAIN OUTCOMES MEASURES: IMCL and intrahepatic
      lipids were measured with proton magnetic resonance spectroscopy ((1)H-MRS). Body
      composition was measured with magnetic resonance imaging. Peak GH was measured
      after stimulation with GHRH-arginine. RESULTS: Obese subjects had higher IMCL,
      intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with
      normal-weight controls. There were strong inverse associations between peak GH
      and both IMCL and intrahepatic lipids independent of age and visceral adiposity.
      There were positive associations between IMCL and intrahepatic lipids with
      measures of insulin resistance and serum triglycerides. CONCLUSION: In
      premenopausal women with obesity, peak GH is inversely associated with IMCL and
      intrahepatic lipids independent of age and visceral adiposity. This suggests that
      low GH may contribute to insulin resistance in obesity through effects on muscle
      and intrahepatic lipids.

PMID- 19602560
TI  - Adipocyte differentiation-related protein and OXPAT in rat and human skeletal
      muscle: involvement in lipid accumulation and type 2 diabetes mellitus.
AB  - SETTING: A disordered lipid metabolism is implicated in the development of
      skeletal muscle insulin resistance. Lipid droplet proteins of the PAT [perilipin,
      adipocyte differentiation-related protein (ADRP), and TIP47] family have been
      shown to regulate lipid accumulation and intracellular metabolism in other
      tissues. OBJECTIVE: This study aimed to explore the role of the PAT proteins
      OXPAT and ADRP in skeletal muscle lipid metabolism and their putative role in
      modulating insulin sensitivity. DESIGN: Muscle OXPAT and ADRP protein content was
      examined during the development of insulin resistance in Zucker diabetic fatty
      (ZDF) rats and in type 2 diabetes patients and BMI-matched control subjects.
      Furthermore, we examined the effect of 8 wk of insulin sensitizing by
      rosiglitazone on muscle OXPAT and ADRP content. RESULTS: OXPAT and ADRP protein
      expression is muscle fiber type specific in humans and rats, with highest protein
      content in fibers containing most intramyocellular lipids (IMCL). Muscle OXPAT
      and ADRP protein content was 2- to 3-fold higher in ZDF rats during the
      progression of type 2 diabetes than in lean normoglycemic control rats, which was
      paralleled by high IMCL levels. Muscle OXPAT and ADRP content, as well as IMCL
      level, was not different between type 2 diabetes patients and control subjects.
      ADRP content was negatively associated with insulin-stimulated glucose uptake (r
      = -0.50; P = 0.017). Interestingly, rosiglitazone treatment decreased muscle
      OXPAT (-29%) and ADRP (-28%) content in diabetes patients, without affecting
      IMCL. CONCLUSIONS: These results indicate involvement of OXPAT and ADRP in
      muscular lipid accumulation and type 2 diabetes.

PMID- 19602561
TI  - Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down
      regulated during diet-induced weight loss.
AB  - CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in
      hypovascular connective tissues. Global gene expression scans show that the TNMD
      gene also is expressed in human adipose tissue and that its expression is
      regulated in response to weight reduction; however, more detailed information is
      lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue
      distribution and TNMD gene expression in human adipose tissue in relation to
      obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene
      expression, tissue distribution, and TNMD gene expression in adipose tissue from
      different depots, from lean and obese subjects, and during diet-induced weight
      reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME
      MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was
      predominantly expressed in sc adipose tissue. TNMD gene expression was higher in
      sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P =
      0.014). In both women and men, TNMD gene expression was significantly higher in
      the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P =
      0.010, respectively). In a multiple linear regression analysis, BMI was a
      significant independent predictor of TNMD gene expression. TNMD gene expression
      was down-regulated during diet-induced weight loss, with a 65% decrease after 18
      wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD
      gene expression is highly affected by obesity, adipose tissue location, and
      weight loss, indicating that TNMD may play a role in adipose tissue function.

PMID- 19602562
TI  - Specificity of screening tests for Cushing's syndrome in an overweight and obese
      population.
AB  - CONTEXT: Recent reports suggest a higher prevalence (1-5%) of Cushing's syndrome
      in certain patient populations with features of the disorder (e.g., diabetes),
      but the prevalence in the overweight and obese population is not known.
      OBJECTIVE: The aim of the study was to evaluate the diagnostic performance of
      screening tests for Cushing's syndrome in overweight and obese subjects with at
      least two other features of the disorder. DESIGN AND SETTING: We conducted a
      cross-sectional prospective study. SUBJECTS AND METHODS: A total of 369 subjects
      (73% female) completed two or three tests: a 24-h urine cortisol, and/or late
      night salivary cortisol, and/or 1 mg dexamethasone suppression test (DST). If any
      result was abnormal [based on laboratory reference range or cortisol after DST >
      or = 1.8 microg/dl (50 nmol/liter)], tests were repeated and/or a dexamethasone
      CRH test was performed. Subjects with abnormal DST results and a low
      dexamethasone level were asked to repeat the test with 2 mg of dexamethasone.
      RESULTS: In addition to obesity, subjects had a mean of five to six features of
      Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities
      to exclude Cushing's syndrome for subjects who completed three tests were: urine
      cortisol, 96% [95% confidence interval (CI), 93-98%]; DST, 90% (95% CI, 87-93%);
      salivary cortisol, 84% by RIA (95% CI, 79-89%) and 92% by liquid chromatography
      tandem mass spectrometry (95% CI, 88-95%). The combined specificity (both tests
      normal) for all combinations of two tests was 84 to 90%, with overlapping CIs.
      CONCLUSION: These data do not support widespread screening of overweight and
      obese subjects for Cushing's syndrome; test results for such patients may be
      falsely abnormal.

PMID- 19602565
TI  - Breast carcinoma--rare types: review of the literature.
AB  - Invasive breast cancer is a heterogeneous disease in its presentation,
      pathological classification and clinical course. However, there are more than a
      dozen variants which are less common but still very well defined by the World
      Health Organization (WHO) classification. The rarity of many of these neoplasms
      does not allow large or randomized studies to define the optimal treatment. Many
      of the descriptions of these cancers are from case reports and small series. Our
      review brings updated information on 16 epithelial subtypes as classified by the
      WHO system with a very concise histopathology description and parameters helpful
      in the clinic. The aim of our review is to provide a tool for breast cancer
      caregivers which will enable a better understanding of the disease and its
      optimal approach to therapy. This may also stand as a clinical framework for a
      future understanding of these rarer breast cancers when gene analysis work is
      reported.

PMID- 19602564
TI  - Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients
      with metastatic breast cancer.
AB  - BACKGROUND: We evaluated the relationship between the detection and prognostic
      significance of circulating tumor cells (CTCs) and sites of metastases detected
      by 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed
      tomography (FDG-PET/CT) in patients with metastatic breast cancer (MBC). PATIENTS
      AND METHODS: From May 2004 to January 2008, 195 patients with
      relapsed/progressive MBC underwent whole-body FDG-PET/CT and provided blood
      samples for assessment of CTC count. RESULTS: Higher CTC numbers were detected in
      patients with bone metastases relative to those with no bone lesions (mean 65.7
      versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to
      those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs
      predicted overall survival (OS) in 108 patients with multiple sites of metastases
      including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111)
      and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with
      human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated
      with trastuzumab-based regimens had <5 CTCs at progression. In multivariate
      analysis, CTCs, but not bone metastases, remained a significant predictor of OS.
      CONCLUSION: Presence of extensive bone metastases as detected by FDG-PET/CT is
      associated with increased CTC numbers in MBC.

PMID- 19602566
TI  - Clinical and dosimetric factors associated with a prolonged feeding tube
      requirement in patients treated with chemoradiotherapy (CRT) for head and neck
      cancers.
AB  - BACKGROUND: Patients treated with chemoradiotherapy (CRT) for head and neck
      cancers often require feeding tubes (FTs) due to toxicity. We sought to identify
      factors associated with a prolonged FT requirement. PATIENTS AND METHODS: We
      retrospectively reviewed 80 patients treated with CRT for head and neck cancers.
      The pharyngeal constrictors (PCs), supraglottic larynx (SGL), and glottic larynx
      (GL) were contoured and the mean radiation doses and the volumes of each
      receiving >40, 50, 60, and 70 Gy (V40, V50, V60, and V70) were determined.
      RESULTS: A total of 33 of 80 patients required a FT either before or during the
      course of CRT. Fifteen patients required the FT for > or = 6 months. On
      univariate analysis, significant factors associated with a prolonged FT
      requirement were mean PC dose, PC-V60, PC-V70, SGL dose, SGL-V70, and advanced T3
      T4 disease. Multivariate analyses found both PC-V70 and T3-T4 disease as
      significant factors .The proportions of patients requiring a FT > or = 6 months
      were 8% and 28% for treatment plans with PC-V70 <30% and > or = 30%,
      respectively. CONCLUSIONS: Increased radiation dose to the PCs is associated with
      a higher risk of a prolonged FT need. Dose sparing of the PC muscles may reduce
      this risk.

PMID- 19602563
TI  - Factors associated with non-adherence to long-term highly active antiretroviral
      therapy: a 10 year follow-up analysis with correction for the bias induced by
      missing data.
AB  - OBJECTIVES: The aim of this study was to identify factors associated with non
      adherence over a 10 year follow-up of the APROCO-COPILOTE cohort during the
      maintenance phase of highly active antiretroviral therapy (HAART). METHODS:
      Overall, 1010 patients participated in this analysis, each having had at least 12
      months of follow-up after HAART initiation and at least one self-reported
      adherence measure available during the follow-up period (month 12-month 120).
      Data collection was based on clinical records and self-administered
      questionnaires that gathered patients' psychosocial characteristics and
      experience with HIV disease and treatment. First, a generalized estimating
      equations (GEE) model was used to identify non-adherence predictors. Secondly, a
      Heckman two-stage approach was used in order to account for missing data bias and
      to measure the extent to which this could affect the results of the first model.
      RESULTS: Non-adherent behaviour was reported by 747 patients (2070 visits). After
      correcting for the bias due to missing data, non-adherence was independently
      associated with side effects, having a three times or more daily dosing regimen,
      experience of being at clinical stage B/C and being diagnosed as HIV-positive for
      <6 months. Non-adherence was more likely among patients who were younger, had
      children, were born in the European Union, had depressive symptoms, consumed
      alcohol daily and declared a lack of support from their main partner. Adjusting
      for missing outcome data changed the pattern of predictors. CONCLUSIONS: Reasons
      for non-adherence depended on both psychosocial conditions and treatment-related
      characteristics. To improve long-term patient outcomes for those at risk of
      adherence failure, tailor-made patient-specific psychosocial interventions and
      regimen-based strategies with improved tolerance need to be implemented.

PMID- 19602568
TI  - Immunological mimicry of PrPC-PrPSc interactions: antibody-induced PrP
      misfolding.
AB  - Prion diseases are associated with the conversion of cellular prion protein
      (PrP(C)) to an abnormal protease-resistant conformational isoform (PrP(Sc)) by
      template-directed conversion. The interaction between PrP(C) and PrP(Sc) is
      mediated by specific sites which have been mapped to six putative 'binding and
      conversion domains' (PrP-BCD) through peptide and antibody competition studies.
      Monoclonal antibodies (mAbs) directed against the bityrosine motif Tyr-Tyr-Arg
      (YYR) specifically recognize PrP(Sc) and other misfolded PrP species. Here, we
      report that select bead-bound PrP-BCD mAbs induce exposure of bityrosine epitopes
      on mouse brain PrP. By competition immunoprecipitation, we show that PrP-BCD mAb
      induced bityrosine exposure occurs at alpha-helices 1 and 3. However, PrP-BCD mAb
      induced PrP(C) misfolding is not accompanied by beta-sheet dissociation, a key
      event in PrP(C) conversion to PrP(Sc), and is not associated with acquisition of
      protease resistance, or the capacity to recruit additional molecules of PrP. Our
      data suggest that mAb mimics of the physical interaction of PrP(C) with PrP(Sc)
      can induce unfolding of specific PrP domains, but that subsequent processes
      (including the energetically unfavorable beta-sheet dissociation) effect isoform
      conversion in prion disease.

PMID- 19602567
TI  - The consequences of pathogenic mutations to the human prion protein.
AB  - Prion diseases, in which the conformational transition of the native prion
      protein (PrP) to a misfolded form causes aggregation and subsequent
      neurodegeneration, have fascinated the scientific community as this transmissible
      disease appears to be purely protein-based. Disease can arise due to genetic
      factors only. At least 30 single point mutations have been indicated to cause
      disease in humans. Somehow, these mutations must influence the stability,
      processing and/or cellular interactions of PrP, such that aggregation can occur
      and disease develops. In this review, the current evidence for such effects of
      single point mutations is discussed, indicating that PrP can be affected in many
      different ways, although questions remain about the mechanism by which mutations
      cause disease.

PMID- 19602570
TI  - Identifying temporally differentially expressed genes through functional
      principal components analysis.
AB  - Time course gene microarray is an important tool to identify genes with
      differential expressions over time. Traditional analysis of variance (ANOVA) type
      of longitudinal investigation may not be applicable because of irregular time
      intervals and possible missingness due to contamination in microarray
      experiments. Functional principal components analysis is proposed to test
      hypotheses in the change of the mean curves. A permutation test under a mild
      assumption is used to make the method more robust. The proposed method
      outperforms the recently developed extraction of differential gene expression and
      a 2-way mixed effects ANOVA under reasonable gene expression models in
      simulation. Real data on transcriptional profiles of blood cells microarray from
      treated and untreated individuals were used to illustrate this method.

PMID- 19602569
TI  - Short protein segments can drive a non-fibrillizing protein into the amyloid
      state.
AB  - Protein fibrils termed amyloid-like are associated with numerous degenerative
      diseases as well as some normal cellular functions. Specific short segments of
      amyloid-forming proteins have been shown to form fibrils themselves. However, it
      has not been shown in general that these segments are capable of driving a
      protein from its native structure into the amyloid state. We applied the 3D
      profile method to identify fibril-forming segments within the amyloid-forming
      human proteins tau, alpha-synuclein, PrP prion and amyloid-beta. Ten segments,
      six to eight residues in length, were chosen and inserted into the C-terminal
      hinge loop of the highly constrained enzyme RNase A, and tested for fibril growth
      and Congo red birefringence. We find that all 10 unique inserts cause RNase A to
      form amyloid-like fibrils which display characteristic yellow to apple-green
      Congo red birefringence when observed with cross polarizers. These six to eight
      residue inserts can fibrillize RNase A and are sufficient for amyloid fibril
      spine formation.

PMID- 19602571
TI  - Coping with temptations and adolescent smoking cessation: an initial
      investigation.
AB  - INTRODUCTION: Although a great deal of research focuses on adolescent cigarette
      smoking, little is known about the process by which adolescents attempt to stop
      smoking. Resisting temptations to smoke is one of the key challenges encountered
      by individuals who attempt smoking cessation. A large body of literature has
      examined coping with temptation among adult smokers, and research on this issue
      for adolescents is lacking. To further our understanding in this area, the
      present study reports on an initial examination of the Smoking Temptation Coping
      Questionnaire (STCQ). The STCQ, which assesses coping in a social pressure
      situation involving cigarettes, was adapted from the Temptation Coping
      Questionnaire, a brief self-report measure of adolescent coping with temptations
      to use alcohol and other drugs. METHODS: The present study included 109
      adolescent participants (aged 14-19 years) in a naturalistic study of smoking
      self-change. Participants completed baseline and 6-month follow-up interviews.
      RESULTS: Exploratory factor analysis of the STCQ coping scale yielded a single
      factor including six strategies for coping with temptations. Analyses provided
      support for the concurrent, predictive, and construct validity of the STCQ. In
      particular, the coping scale score significantly predicted prospective duration
      of abstinence for adolescents who engaged in smoking cessation efforts.
      DISCUSSION: These results provide preliminary support for the utility of the
      STCQ. In addition, findings support the role of temptation coping in the
      adolescent smoking cessation process.

PMID- 19602572
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha enhances
      antiproliferative activity of 5'-deoxy-5-fluorouridine in cancer cells through
      induction of uridine phosphorylase.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)
      is capable of coactivating several nuclear receptors and transcription factors
      that participate in the regulation of multiple metabolic processes, including
      gluconeogenesis, mitochondrial biogenesis, and adaptive thermogenesis. Uridine
      phosphorylase (UPase) catalyzes the reversible conversion of uridine into uracil
      and contributes to the antineoplastic activity of 5'-deoxy-5-fluorouridine (5'
      DFUR) and homeostasis of uridine levels in plasma and tissues. This study
      demonstrates uridine phosphorylase as a novel target gene of PGC-1alpha, which
      induces the transcription and enzymatic activity of UPase in various cancer cells
      and thus augments their susceptibility to 5'-DFUR. PGC-1alpha-induced activation
      of UPase expression occurs at its transcription level that is mediated by an
      estrogen-related receptor (ERR) binding site (-1078 to -1070 base pairs) mapped
      in the promoter region of UPase gene. Our mutational studies using luciferase
      reporter construct together with electrophoretic mobility shift assays confirm
      the binding of ERR to PGC-1alpha-responsive element. Moreover, the inhibition of
      PGC-1alpha/ERRalpha-dependent signaling by 3-[4-(2,4-bis
      trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4
      thiadiazol-2-yl)acrylamide (XCT790) compromises the ability of PGC-1alpha to
      induce the transcript of UPase, indicating PGC-1alpha-dependent and ERRalpha
      mediated up-regulation of UPase. Finally, the overexpression of PGC-1alpha
      sensitizes breast and colon cancer cells to growth inhibition by 5'-DFUR
      presumably by inducing apoptosis in tumor cells and XCT790 can inhibit the
      process. Taken together, our results corroborate the regulatory function of PGC
      1alpha in uridine homeostasis and imply its links with the energy metabolism. The
      mechanistic elucidation of this association between both cellular pathways should
      advance the clinical use of 5-fluorouracil-based chemotherapy.

PMID- 19602574
TI  - Biologically relevant exposure science for 21st century toxicity testing.
AB  - High visibility efforts in toxicity testing and computational toxicology
      including the recent National Research Council of the National Academies (NRC)
      report, Toxicity Testing in the 21st Century: A Vision and Strategy (NRC, 2007a),
      raise important research questions and opportunities for the field of exposure
      science. The authors of the National Academies report (NRC, 2007a) emphasize that
      population-based data and human exposure information are required at each step of
      their vision for toxicity testing and that these data will continue to play a
      critical role in both guiding development and use of the toxicity information. In
      fact, state-of-the-art exposure science is essential for translation of toxicity
      data to assess potential for risk to individuals and populations and to inform
      public health decisions. As we move forward to implement the NRC vision, a
      transformational change in exposure science is required. Application of a fresh
      perspective and novel techniques to capture critical determinants at biologically
      motivated resolution for translation from controlled in vitro systems to the open
      multifactorial system of real-world human-environment interaction will be
      critical. Development of an exposure ontology and knowledge base will facilitate
      extension of network analysis to the individual and population for translating
      toxicity information and assessing health risk. Such a sea change in exposure
      science is required to incorporate consideration of lifestage, genetic
      susceptibility, and interaction of nonchemical stressors for holistic assessment
      of risk factors associated with complex environmental disease. A new generation
      of scientific tools has emerged to rapidly measure signals from cells, tissues,
      and organisms following exposure to chemicals. Investment in 21st century
      exposure science is now required to fully realize the potential of the NRC vision
      for toxicity testing.

PMID- 19602573
TI  - Group X phospholipase A2 stimulates the proliferation of colon cancer cells by
      producing various lipid mediators.
AB  - Among mammalian secreted phospholipases A2 (sPLA(2)s), the group X enzyme has the
      most potent hydrolyzing capacity toward phosphatidylcholine, the major
      phospholipid of cell membrane and lipoproteins. This enzyme has recently been
      implicated in chronic inflammatory diseases such as atherosclerosis and asthma
      and may also play a role in colon tumorigenesis. We show here that group X
      sPLA(2) [mouse (m)GX] is one of the most highly expressed PLA(2) in the mouse
      colon and that recombinant mouse and human enzymes stimulate proliferation and
      mitogen-activated protein kinase activation of various colon cell lines,
      including Colon-26 cancer cells. Among various recombinant sPLA(2)s, mGX is the
      most potent enzyme to stimulate cell proliferation. Based on the use of sPLA(2)
      inhibitors, catalytic site mutants, and small interfering RNA silencing of
      cytosolic PLA(2)alpha and M-type sPLA(2) receptor, we demonstrate that mGX
      promotes cell proliferation independently of the receptor and via its intrinsic
      catalytic activity and production of free arachidonic acid and lysophospholipids,
      which are mitogenic by themselves. mGX can also elicit the production of large
      amounts of prostaglandin E2 and other eicosanoids from Colon-26 cells, but these
      lipid mediators do not play a role in mGX-induced cell proliferation because
      inhibitors of cyclooxygenases and lipoxygenases do not prevent sPLA(2) mitogenic
      effects. Together, our results indicate that group X sPLA(2) may play an
      important role in colon tumorigenesis by promoting cancer cell proliferation and
      releasing various lipid mediators involved in other key events in cancer
      progression.

PMID- 19602575
TI  - Maternal and infant characteristics associated with human milk feeding in very
      low birth weight infants.
AB  - This study identified maternal and infant characteristics predicting human milk
      (HM) feeding in very low birth weight (VLBW) infants whose mothers (n = 184)
      participated in a study of lactation counseling and initiated milk expression.
      Data were collected prospectively, by maternal interview and medical record
      review. During hospitalization, 159 (86%) infants received at least 50% HM
      proportion of feedings in the first 2 weeks of life, and 114 (62%) received some
      HM until the day of hospital discharge. Analysis showed plan to breastfeed was
      the strongest predictor of initiation and duration of HM feeding. Greater than 12
      years of education, respiratory distress syndrome, Apgar score >6, and female
      gender were significant predictors, and no perinatal hypertensive disorder, white
      race, and mechanical ventilation were marginal predictors of HM feeding. Women
      with a high-risk pregnancy should be provided education about the benefits of
      breastfeeding for infants who are likely to be born prematurely.

PMID- 19602576
TI  - Relactation, translactation, and breast-orogastric tube as transition methods in
      feeding preterm babies.
AB  - The transition from tube feeding to exclusive breastfeeding represents an
      important period for preterm babies because of their clinical fragility and
      immature development. This study describes this transition in preterm infants in
      relation to different feeding approaches: relactation, translactation, and breast
      orogastric (OG) tube, considering the duration of the transition, weight gain in
      the transition, feeding-related problems, and breastfeeding status at discharge.
      This is a descriptive study of a series of 432 babies using retrospective data
      from the medical records at the IMIP Kangaroo Mother Care Unit, in the northeast
      of Brazil. At discharge, the percentage of babies who were exclusively breastfed
      in the relactation, translactation, and breast-OG tube groups were 85%, 100%, and
      100%, respectively, with a satisfactory transition time and weight gain and with
      1.6% of cases with feeding-related problems. The results showed that the
      relactation, translactation, and breast-OG tube seem to be efficient methods in
      the feeding transition of preterm infants.

PMID- 19602577
TI  - Gudden's ventral tegmental nucleus is vital for memory: re-evaluating
      diencephalic inputs for amnesia.
AB  - Mammillary body atrophy is present in a number of neurological conditions and
      recent clinical findings highlight the importance of these nuclei for memory.
      While most accounts of diencephalic amnesia emphasize the functional importance
      of the hippocampal projections to the mammillary bodies, the present study tested
      the importance of the other major input to the mammillary bodies, the projections
      from the ventral tegmental nucleus of Gudden (VTNg). Although the VTNg, and its
      projections to the mammillary bodies, is present across species, the size and
      location of this structure has made it an extremely difficult structure to assess
      in primates. The effects of selective, neurotoxic lesions of the VTNg were,
      therefore, assessed in rats. The animals with these lesions were impaired on a
      series of spatial learning tasks, namely delayed-matching-to-place in the water
      maze, T-maze alternation and working memory in the radial arm maze. Normal
      performance on these tasks is dependent on those brain structures (e.g.
      hippocampus and mammillary bodies) that are now assumed to cause anterograde
      amnesia when damaged in humans. In contrast, the same rats with ventral tegmental
      nucleus lesions performed normally on two control tasks: the acquisition and
      subsequent reversal of an egocentric discrimination task and a visually cued task
      in the water maze. This study provides the first clear evidence that the VTNg is
      critical for memory, and consequently indicates that diencephalic-hippocampal
      models of memory should be extended to incorporate the limbic midbrain.

PMID- 19602578
TI  - Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by
      activation of exocytosis.
AB  - Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets
      responsible for the degradation of proteoglycans such as perlecan and dermatan
      sulfate. Previous findings of our group demonstrated the involvement of IDS in
      the normal pathway of lysosomal degradation of secretory peptides, suggesting a
      role of this enzyme in beta-cell secretory functionality. The present study was
      undertaken to characterize the effect of IDS overexpression on insulin release.
      INS1E cells were transiently transfected with a construct encoding human IDS
      (hIDS). hIDS overexpression was associated with a gain of function detected by a
      reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated
      insulin secretory response compared with controls (61%) with no changes in
      insulin mRNA levels or insulin peptide content. Results on quantification of the
      exocytotic process showed a significant increase in hIDS-transfected cells
      compared with controls. Furthermore, ultramorphological analysis demonstrated an
      increase in the number of granules in the immediate vicinity of the plasma
      membrane in hIDS-transfected cells and a decrease in total vesicles per square
      micrometer. hIDS overexpression induced phosphorylation of protein kinase C (PKC)
      alpha and its newly myristoylated alanine-rich C kinase substrate, MARCKS. We
      conclude that IDS has a role in glucose-stimulated insulin secretion via a
      mechanism that involves the activation of exocytosis through phosphorylation of
      PKCalpha and MARCKS.

PMID- 19602580
TI  - Motor unit number estimate as a predictor of motor dysfunction in an animal model
      of type 1 diabetes.
AB  - Peripheral neuropathy is a common complication of diabetes that leads to severe
      morbidity. In this study, we investigated the sensitivity of motor unit number
      estimate (MUNE) to detect early motor axon dysfunction in streptozotocin (STZ)
      treated mice. We compared the findings with in vitro changes in the morphology
      and electrophysiology of the neuromuscular junction. Adult Thy1-YFP and Swiss
      Webster mice were made diabetic following three interdaily intraperitoneal STZ
      injections. Splay testing and rotarod performance assessed motor activity for 6
      wk. Electromyography was carried out in the same time course, and compound muscle
      action potential (CMAP) amplitude, latency, and MUNE were estimated. Two
      electrode voltage clamp was used to calculate quantal content (QC) of evoked
      transmitter release. We found that an early reduction in MUNE was evident before
      a detectable decline of motor activity. CMAP amplitude was not altered. MUNE
      decrease accompanied a drop of end-plate current amplitude and QC. We also
      observed small axonal loss, sprouting of nerve endings, and fragmentation of
      acetylcholine receptor clusters at the motor end plate. Our results suggest an
      early remodeling of motor units through the course of diabetic neuropathy, which
      can be readily detected by the MUNE technique. The early detection of MUNE
      anomalies is significant because it suggests that molecular changes associated
      with pathology and leading to neurodegeneration might already be occurring at
      this stage. Therefore, trials of interventions to prevent motor axon dysfunction
      in diabetic neuropathy should be administered at early stages of the disorder.

PMID- 19602581
TI  - Role of lipid-derived mediators in skeletal muscle insulin resistance.
AB  - Imbalance between nutritional intake and energy expenditure has been described to
      culminate in obesity, which predisposes to insulin resistance and type 2 diabetes
      mellitus. In such states of energy oversupply, excess amounts of lipids are
      available in tissues and circulation. Over the past years, an increasingly
      important role in development of skeletal muscle (SkM) insulin resistance has
      been attributed to lipids and impaired fatty acid metabolism. In this review, we
      reflect the current state of knowledge about the effects of various lipid-derived
      mediators on SkM insulin sensitivity. Furthermore, potential mechanisms
      underlying the biogenesis of intramyocellular ectopic lipid stores are discussed.
      Previously, a pivotal role was attributed to mitochondrial dysfunction. However,
      results of recent studies have suggested an important role for exercise
      deficiency, accompanied by decreased expression levels of peroxisome proliferator
      activated receptor-gamma coactivator-1alpha and subsequent, incomplete beta
      oxidation. Additionally, we summarize the implications of increased levels of
      lipid-derived endocannabinoids (ECs) for metabolic control in peripheral tissue
      and highlight the benefits of targeting the EC system.

PMID- 19602579
TI  - Oxidative stress and dysregulation of the taurine transporter in high-glucose
      exposed human Schwann cells: implications for pathogenesis of diabetic
      neuropathy.
AB  - In human Schwann cells, the role of taurine in regulating glucose-induced changes
      in antioxidant defense systems has been examined. Treatment with high glucose for
      7 days induced reactive oxygen species, increased 4-hydroxynoneal adducts (20 +/-
      5%, P < 0.05) and poly(ADP-ribosyl)ated proteins (40 +/- 13%, P < 0.05).
      Increases in these markers of oxidative stress were reversed by simultaneous
      incubation in 0.25 mM taurine. Both high glucose and taurine independently
      increased superoxide dismutase and catalase activity and decreased glutathione
      levels, but their effects were not additive. Glucose reduced taurine transporter
      (TauT) mRNA and protein in a dose-dependent manner with maximal decreases of 66
      +/- 6 and 63 +/- 12%, respectively (P < 0.05 both). The V(max) for taurine uptake
      was decreased in 30 mM glucose from 61 +/- 5 to 42 +/- 3 pmol x min(-1) x mg
      protein(-1) (P < 0.001). Glucose-induced TauT downregulation could be reversed by
      inhibition of aldose reductase, a pathway that depletes NADPH and increases
      osmotic stress and protein glycation. TauT protein was increased more than
      threefold, and the V(max) for taurine uptake doubled (P < 0.05 both) by
      prooxidants. TauT downregulation was reversed both by treatment with the
      antioxidant alpha-lipoic acid, which increased TauT mRNA by 60% and V(max) by 50%
      (P < 0.05 both), and by the aldose reductase inhibitor sorbinil, which increased
      TauT mRNA 380% and V(max) by 98% (P < 0.01 both). These data highlight the
      potential therapeutic benefits of taurine supplementation in diabetic
      complications and provide mechanisms whereby taurine restoration could be
      achieved in order to prevent or reverse diabetic complications.

PMID- 19602582
TI  - A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like
      growth factor I axis and glucose intolerance.
AB  - Ghrelin is a stomach-derived peptide that has growth hormone-stimulating and
      orexigenic activities. Although there have been several reports of ghrelinoma
      cases, only a few cases have elevated circulating ghrelin levels, hampering the
      investigation of pathophysiological features of ghrelinoma and chronic effects of
      ghrelin excess. Furthermore, standard transgenic technique has resulted in
      desacyl ghrelin production only because of the limited tissue expression of
      ghrelin O-acyltransferase, which mediates acylation of ghrelin. Accordingly, we
      attempted to create ghrelin promoter SV40 T-antigen transgenic (GP-Tag Tg) mice,
      in which ghrelin-producing cells continued to proliferate and finally developed
      into ghrelinoma. Adult GP-Tag Tg mice showed elevated plasma ghrelin levels with
      preserved physiological regulation. Adult GP-Tag Tg mice with increased plasma
      ghrelin levels exhibited elevated IGF-I levels despite poor nutrition. Although
      basal growth hormone levels were not changed, those after growth hormone
      releasing hormone injection tended to be higher. These results indicate that
      chronic elevation of ghrelin activates GH-IGF-I axis. In addition, GP-Tag Tg mice
      demonstrated glucose intolerance. Insulin secretion by glucose tolerance tests
      was significantly attenuated in GP-Tag Tg, whereas insulin sensitivity determined
      by insulin tolerance tests was preserved, indicating that chronic elevation of
      ghrelin suppresses insulin secretion and leads to glucose intorelance. Thus, we
      successfully generated a Tg model of ghrelinoma, which is a good tool to
      investigate chronic effects of ghrelin excess. Moreover, their characteristic
      features could be a hint on ghrelinoma.

PMID- 19602583
TI  - Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases
      fetal amino acid oxidation.
AB  - Protein supplementation during human pregnancy does not improve fetal growth and
      may increase small-for-gestational-age birth rates and mortality. To define
      possible mechanisms, sheep with twin pregnancies were infused with amino acids
      (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In
      the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations
      were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA
      group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P <
      0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005),
      and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001)
      were decreased on day 4 compared with day 0. Fetal leucine disposal did not
      change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C),
      but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16
      vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen
      utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29
      micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal
      protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C),
      release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(
      1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x
      min(-1) x kg(-1)) did not change. Consistent with these data, there was no change
      in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein
      synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased
      concentrations of certain essential amino acids, increased amino acid oxidation,
      fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal
      toxicity during maternal amino acid supplementation.

PMID- 19602584
TI  - Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in
      vivo in human skeletal muscle.
AB  - In animal models, administration of the adenosine analog AICA-riboside has shown
      beneficial effects on ischemia-reperfusion injury and glucose homeostasis. The
      vascular and/or metabolic effects of AICA-riboside administration in humans
      remain to be established. AICA-riboside was infused intra-arterially in four
      different dosages up to 8 mg x min(-1) x dl(-1) in 24 healthy subjects. Forearm
      blood flow (FBF) and glucose uptake and plasma glucose, free fatty acid, and AICA
      riboside concentrations were assessed. We also combined AICA-riboside infusion (2
      mg x min(-1) x dl(-1)) with the intra-arterial administration of the adenosine
      receptor antagonist caffeine (90 microg x min(-1) x dl(-1); n = 6) and with the
      endothelial NO synthase inhibitor l-NMMA (0.4 mg x min(-1) x dl(-1); n = 6).
      Additional in vitro experiments were performed to explain our in vivo effects of
      AICA-riboside in humans. AICA-riboside increased FBF dose dependently from 2.0 +/
      0.2 to 13.2 +/- 1.9 ml x min(-1) x dl(-1) maximally (P < 0.05 for all dosages).
      The latter was not reduced by caffeine administration but was significantly
      attenuated by l-NMMA infusion. Despite high plasma AICA-riboside concentrations,
      forearm glucose uptake did not change. In vitro experiments showed rapid uptake
      of AICA-riboside by the equilibrative nucleoside transporter in erythrocytes and
      subsequent phosphorylation to AICA-ribotide. We conclude that AICA-riboside
      induces a potent vasodilator response in humans that is mediated by NO. Despite
      high local plasma concentrations, AICA-riboside does not increase skeletal muscle
      glucose uptake.

PMID- 19602585
TI  - Pancreatic beta-cell overexpression of the glucagon receptor gene results in
      enhanced beta-cell function and mass.
AB  - In addition to its primary role in regulating glucose production from the liver,
      glucagon has many other actions, reflected by the wide tissue distribution of the
      glucagon receptor (Gcgr). To investigate the role of glucagon in the regulation
      of insulin secretion and whole body glucose homeostasis in vivo, we generated
      mice overexpressing the Gcgr specifically on pancreatic beta-cells (RIP-Gcgr). In
      vivo and in vitro insulin secretion in response to glucagon and glucose was
      increased 1.7- to 3.9-fold in RIP-Gcgr mice compared with controls. Consistent
      with the observed increase in insulin release in response to glucagon and
      glucose, the glucose excursion resulting from both a glucagon challenge and
      intraperitoneal glucose tolerance test (IPGTT) was significantly reduced in RIP
      Gcgr mice compared with controls. However, RIP-Gcgr mice display similar glucose
      responses to an insulin challenge. beta-Cell mass and pancreatic insulin content
      were also increased (20 and 50%, respectively) in RIP-Gcgr mice compared with
      controls. When fed a high-fat diet (HFD), both control and RIP-Gcgr mice
      developed similar degrees of obesity and insulin resistance. However, the
      severity of both fasting hyperglycemia and impaired glucose tolerance (IGT) were
      reduced in RIP-Gcgr mice compared with controls. Furthermore, the insulin
      response of RIP-Gcgr mice to an IPGTT was twice that of controls when fed the
      HFD. These data indicate that increased pancreatic beta-cell expression of the
      Gcgr increased insulin secretion, pancreatic insulin content, beta-cell mass,
      and, when mice were fed a HFD, partially protected against hyperglycemia and IGT.

PMID- 19602586
TI  - Overexpression of extracellular superoxide dismutase attenuates heparanase
      expression and inhibits breast carcinoma cell growth and invasion.
AB  - Increased expression of heparanase stimulates the progression of various human
      cancers, including breast cancer. Therefore, a deeper understanding of the
      mechanisms involved in regulating heparanase is critical in developing effective
      treatments for heparanase-overexpressing cancers. In this study, we investigated
      the potential use of extracellular superoxide dismutase (EcSOD) to enhance the
      inhibitory effects of heparin/low molecular weight heparin (LMWH) in breast
      cancer cells. EcSOD binds to cell surfaces and the extracellular matrix through
      heparin-binding domain (HBD). Deleting this HBD rendered the protein a more
      potent inhibitor of breast cancer growth, survival, and invasion. Among the
      treatment combinations examined, EcSODDeltaHBD plus LMWH provided the best tumor
      suppressive effects in inhibiting breast cancer growth and invasion in vitro. We
      have further shown that overexpression of EcSOD decreased accumulation of
      vascular endothelial growth factor in the culture medium and increased the level
      of intact cell surface-associated heparan sulfate, thus implicating inhibition of
      heparanase expression as a potential mechanism. Overexpression of EcSOD inhibited
      steady-state heparanase mRNA levels by >50% as determined by quantitative reverse
      transcription-PCR. Moreover, heparanase promoter activation was suppressed by
      EcSOD as indicated by a luciferase reporter assay. These findings reveal a
      previously unrecognized molecular pathway showing that regulation of heparanase
      transcription can be mediated by oxidative stress. Our study implies that
      overexpression of EcSOD is a promising strategy to enhance the efficacy of
      heparin/LMWH by inhibiting heparanase as a novel treatment for breast cancer.

PMID- 19602587
TI  - Signaling events downstream of mammalian target of rapamycin complex 2 are
      attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor
      suppressors.
AB  - Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic
      disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis. Their
      gene products form a complex that is a critical negative regulator of mammalian
      target of rapamycin (mTOR) complex 1 (mTORC1) and cell growth. We recently found
      that the TSC1-TSC2 complex promotes the activity of mTOR complex 2 (mTORC2), an
      upstream activator of Akt, and this occurs independent of its inhibitory effects
      on mTORC1. Loss of mTORC2 activity in cells lacking the TSC1-TSC2 complex,
      coupled with mTORC1-mediated feedback mechanisms, leads to strong attenuation of
      the growth factor-stimulated phosphorylation of Akt on S473. In this study, we
      show that both phosphatidylinositol 3-kinase-dependent and phosphatidylinositol 3
      kinase-independent mTORC2 substrates are affected by loss of the TSC1-TSC2
      complex in cell culture models and kidney tumors from both Tsc2(+/-) mice
      (adenoma) and TSC patients (angiomyolipoma). These mTORC2 targets are all members
      of the AGC kinase family and include Akt, protein kinase Calpha, and serum and
      glucocorticoid-induced protein kinase 1. We also show that the TSC1-TSC2 complex
      can directly stimulate the in vitro kinase activity of mTORC2. The interaction
      between these two complexes is mediated primarily through regions on TSC2 and a
      core component of mTORC2 called Rictor. Hence, loss of the TSC tumor suppressors
      results in elevated mTORC1 signaling and attenuated mTORC2 signaling. These
      findings suggest that the TSC1-TSC2 complex plays opposing roles in tumor
      progression, both blocking and promoting specific oncogenic pathways through its
      effects on mTORC1 inhibition and mTORC2 activation, respectively.

PMID- 19602590
TI  - Helicobacter pylori infection and gastric cancer risk: evaluation of 15 H. pylori
      proteins determined by novel multiplex serology.
AB  - Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The
      association likely has been underestimated in the past due to disease-related
      clearance of the infection. On the other hand, only a minority of the infected
      individuals develop GC, and better risk stratification is therefore highly
      desirable. We aimed to assess the association of GC with antibodies to 15
      individual H. pylori proteins, determined by novel multiplex serology, to
      identify potentially relevant risk markers. This analysis was based on 123 GC
      cases aged 50 to 74 years and 492 age-matched and sex-matched controls from
      Saarland, Germany. Eight of the antibodies were significantly associated with
      noncardia GC and seven of them were significantly related to GC at any site. More
      pronounced associations were observed for noncardia GC; adjusted odds ratios (95%
      confidence intervals) ranged from 1.60 (1.01-2.54) for HyuA to 5.63 (3.20-9.91)
      for cytotoxin-associated antigen A (CagA). A dose-response relationship was found
      between the number of seropositivities and GC (P < 0.001). The seropositivities
      of CagA and GroEL were found to be independent predictors of GC, which were
      strongly related to GC risk in a dose-response manner (P < 0.001). In conclusion,
      GroEL was identified as a new independent risk marker that may contribute to
      enhanced quantification of H. pylori-related GC risk.

PMID- 19602589
TI  - The G protein-coupled receptor 87 is necessary for p53-dependent cell survival in
      response to genotoxic stress.
AB  - p53 regulates an array of target genes, which mediates p53 tumor suppression by
      inducing cell cycle arrest, apoptosis, and cell survival. G protein-coupled
      receptors belong to a superfamily of cell surface molecules and are known to
      regulate cell proliferation, migration, and survival. Here, we found that G
      protein-coupled receptor 87 (GPR87) was up-regulated by p53 and by DNA damage in
      a p53-dependent manner. We also found that p53 directly regulated GPR87
      potentially via a p53-responsive element in the GPR87 gene. To investigate the
      role of GPR87 in the p53 pathway, we generated multiple RKO and MCF7 cell lines
      in that GPR87 can be inducibly overexpressed or knocked down by a tetracycline
      inducible system. We found that overexpression of GPR87 had little effect on cell
      growth. However, GPR87 knockdown sensitized cancer cells to DNA damage-induced
      growth suppression via enhanced p53 stabilization and activation. Importantly,
      the prosurvival activity of GPR87 can be reversed by knockdown of p53. Together,
      our results suggested that GPR87 is essential for p53-dependent cell survival in
      response to DNA damage. Thus, due to its expression on the cell surface and its
      role in cell survival, GPR87 may be explored as a novel therapeutic target for
      cancer treatment and prevention.

PMID- 19602588
TI  - 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the
      phosphatidylinositol 3-kinase pathway in breast carcinoma.
AB  - Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase
      (PI3K) pathway during cancer development by increasing levels of
      phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent
      kinase 1 (PDK1) is the first node of the PI3K signal output and is required for
      activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through
      interactions with their pleckstrin homology domains, allowing PDK1 to activate
      AKT by phosphorylating it at residue threonine-308. We show that total PDK1
      protein and mRNA were overexpressed in a majority of human breast cancers and
      that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We
      found that increased PDPK1 copy number was associated with upstream pathway
      lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient
      survival. Examination of an independent set of breast cancers and tumor cell
      lines derived from multiple forms of human cancers also found increased PDK1
      protein levels associated with such upstream pathway lesions. In human mammary
      cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate
      cell growth and migration, and rendered cells more resistant to PDK1 and PI3K
      inhibition. After orthotopic transplantation, PDK1 overexpression was not
      oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our
      studies argue that PDK1 overexpression and increased PDPK1 copy number are common
      occurrences in cancer that potentiate the oncogenic effect of upstream lesions on
      the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical
      component of oncogenic PI3K signaling in breast cancer.

PMID- 19602591
TI  - Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells.
AB  - Estrogen receptor beta (ERbeta) is the predominant ER in the colorectal
      epithelium. Compared with normal colon tissue, ERbeta expression is reduced in
      colorectal cancer. Our hypothesis is that ERbeta inhibits proliferation of colon
      cancer cells. Hence, the aim of this study has been to investigate the molecular
      function of ERbeta in colon cancer cells, focusing on cell cycle regulation.
      SW480 colon cancer cells have been lentivirus transduced with ERbeta expression
      construct with or without mutated DNA-binding domain or an empty control vector.
      Expression of ERbeta resulted in inhibition of proliferation and G(1) phase cell
      cycle arrest and this effect was dependent on a functional DNA-binding region. c
      Myc is overexpressed in an overwhelming majority of colorectal tumors. By Western
      blot and real-time PCR, we found c-Myc to be down-regulated in the ERbeta
      expressing cells. Furthermore, the c-Myc target gene p21((Waf1/Cip1)) was induced
      and Cdc25A was reduced by ERbeta at the transcriptional level. The second cdk2
      inhibitor, p27(Kip1), was induced by ERbeta, but this regulation occurred at the
      posttranscriptional level, probably through ERbeta-mediated repression of the F
      box protein p45(Skp2). Expression of the ERbeta-variant with mutated DNA binding
      domain resulted in completely different cell cycle gene regulation. We performed
      in vivo studies with SW480 cells +/- ERbeta transplanted into severe combined
      immunodeficient/beige mice; after three weeks of ERbeta-expression, a 70%
      reduction of tumor volume was seen. Our results show that ERbeta inhibits
      proliferation as well as colon cancer xenograft growth, probably as a consequence
      of ERbeta-mediated inhibition of cell-cycle pathways. Furthermore, this ERbeta
      mediated cell cycle repression is dependent on functional ERE binding.

PMID- 19602592
TI  - Polycomb CBX7 promotes initiation of heritable repression of genes frequently
      silenced with cancer-specific DNA hypermethylation.
AB  - Epigenetic silencing of genes in association with aberrant promoter DNA
      hypermethylation has emerged as a significant mechanism in the development of
      human cancers. Such genes are also often targets of the polycomb group repressive
      complexes in embryonic cells. The polycomb repressive complex 2 (PRC2) has been
      best studied in this regard. We now examine a link between PRC1 and cancer
      specific gene silencing. Here, we show a novel and direct association between a
      constituent of the PRC1 complex, CBX7, with gene repression and promoter DNA
      hypermethylation of genes frequently silenced in cancer. CBX7 is able to complex
      with DNA methyltransferase (DNMT) enzymes, leading us to explore a role for CBX7
      in maintenance and initiation of gene silencing. Knockdown of CBX7 was unable to
      relieve suppression of deeply silenced genes in cancer cells; however, in
      embryonal carcinoma (EC) cells, CBX7 can initiate stable repression of genes that
      are frequently silenced in adult cancers. Furthermore, we are able to observe
      assembly of DNMTs at CBX7 target gene promoters. Sustained expression of CBX7 in
      EC cells confers a growth advantage and resistance to retinoic acid-induced
      differentiation. In this setting, especially, there is increased promoter DNA
      hypermethylation for many genes by analysis of specific genes, as well as through
      epigenomic studies. Our results allow us to propose a potential mechanism through
      assembly of novel repressive complexes, by which the polycomb component of PRC1
      can promote the initiation of epigenetic changes involving abnormal DNA
      hypermethylation of genes frequently silenced in adult cancers.

PMID- 19602593
TI  - Cetuximab/C225-induced intracellular trafficking of epidermal growth factor
      receptor.
AB  - The monoclonal antibody C225 interacts with the ectodomain of the epidermal
      growth factor (EGF) receptor (EGFR) to block ligand binding and initiates
      receptor endocytosis and intracellular trafficking. The data herein show that
      C225-dependent EGFR trafficking relocalizes the receptor to the endoplasmic
      reticulum (ER) and nucleus. This mechanism, which also involves interaction of
      the C225-internalized receptor with the Sec61 translocon within the ER, is, in
      most respects, analogous to the pathway previously described for EGF-induced
      trafficking to the ER and nucleus. However, although inhibition of receptor
      tyrosine kinase activity blocks EGF-induced nuclear localization of the receptor,
      the same kinase inhibitors stimulate C225-dependent nuclear localization of EGFR
      in the nucleus. In contrast, the kinase inhibitor Lapatinib fails to stimulate
      nuclear accumulation of the receptor in C225-treated cells and does not provoke
      receptor dimerization as do inhibitors that recognize the open conformation of
      the receptor kinase. This suggests that inhibitor-dependent receptor dimerization
      may facilitate C225-induced receptor trafficking.

PMID- 19602594
TI  - Kinome profiling of chondrosarcoma reveals SRC-pathway activity and dasatinib as
      option for treatment.
AB  - Chondrosarcomas are notorious for their resistance to conventional chemotherapy
      and radiotherapy, indicating there are no curative treatment possibilities for
      patients with inoperable or metastatic disease. We therefore explored the
      existence of molecular targets for systemic treatment of chondrosarcoma using
      kinome profiling. Peptide array was performed for four chondrosarcoma cell lines
      and nine primary chondrosarcoma cultures with GIST882, MSCs, and colorectal
      cancer cell lines as controls. Activity of kinases was verified using immunoblot,
      and active Src- and platelet-derived growth factor receptor (PDGFR) signaling
      were further explored using imatinib and dasatinib on chondrosarcoma in vitro.
      The AKT1/GSK3B pathway was clearly active in chondrosarcoma. In addition, the
      PDGFR pathway and the Src kinase family were active. PDGFR and Src kinases can be
      inhibited by imatinib and dasatinib, respectively. Although imatinib did not show
      any effect on chondrosarcoma cell cultures, dasatinib showed a decrease in cell
      viability at nanomolar concentrations in seven of nine chondrosarcoma cultures.
      However, inhibition of phosphorylated Src (Y419) was found both in responsive and
      nonresponsive cells. In conclusion, using kinome profiling, we found the Src
      pathway to be active in chondrosarcoma. Moreover, we showed in vitro that the
      inhibitor of the Src pathway, dasatinib, may provide a potential therapeutic
      benefit for chondrosarcoma patients who are not eligible for surgery.

PMID- 19602596
TI  - Loss of RhoB expression promotes migration and invasion of human bronchial cells
      via activation of AKT1.
AB  - Lung cancer is the leading cause of cancer-related death worldwide, mainly due to
      its highly metastatic properties. Previously, we reported an inverse correlation
      between RhoB expression and the progression of the lung cancer, occurring between
      preinvasive and invasive tumors. Herein, we mimicked the loss of RhoB observed
      throughout lung oncogenesis with RNA interference in nontumoral bronchial cell
      lines and analyzed the consequences on both cell transformation and invasion.
      Down-regulation of RhoB did not modify the cell growth properties but did promote
      migration and invasiveness. Furthermore, RhoB depletion was accompanied by
      modifications of actin and cell adhesion. The specific activation of the Akt1
      isoform and Rac1 was found to be critical for this RhoB-mediated regulation of
      migration. Lastly, we showed that RhoB down-regulation consecutive to K-RasV12
      cell transformation is critical for cell motility but not for cell proliferation.
      We propose that RhoB loss during lung cancer progression relates to the
      acquisition of invasiveness mediated by the phosphatidylinositol 3-kinase
      (PI3K)/AKT and Rac1 pathways rather than to tumor initiation.

PMID- 19602598
TI  - Miseries of an author.

PMID- 19602595
TI  - CCL5-mediated endogenous antitumor immunity elicited by adoptively transferred
      lymphocytes and dendritic cell depletion.
AB  - Adoptive transfer of antitumor T cells is a promisingly effective therapy for
      various cancers, but its effect on endogenous antitumor immune mechanisms remains
      largely unknown. Here, we show that the administration of naive T cells de novo
      primed for only 7 days against tumor antigens resulted in the durable rejection
      of otherwise lethal ovarian cancers when coupled with the depletion of tumor
      associated immunosuppressive dendritic cells (DC). Therapeutic activity required
      tumor antigen specificity and perforin expression by the adoptively transferred T
      cells, but not IFN-gamma production. Importantly, these shortly primed T cells
      secreted large amounts of CCL5, which was required for their therapeutic benefit.
      Accordingly, transferred T cells recruited CCR5(+) DCs into the tumor, where they
      showed distinct immunostimulatory attributes. Activated CCR5(+) host T cells with
      antitumor activity also accumulated at tumor locations, and endogenous tumor
      specific memory T cells remained elevated after the disappearance of transferred
      lymphocytes. Therefore, persistent, long-lived antitumor immunity was triggered
      by the administration of ex vivo activated T cells, but was directly mediated by
      immune cells of host origin. Our data unveil a CCL5-dependent mechanism of
      awakening endogenous antitumor immunity triggered by ex vivo expanded T cells,
      which is augmented by tumor-specific targeting of the cancer microenvironment.

PMID- 19602597
TI  - G(alpha)12-mediated pathway promotes invasiveness of nasopharyngeal carcinoma by
      modulating actin cytoskeleton reorganization.
AB  - The molecular mechanisms behind the aggressiveness of nasopharyngeal carcinoma
      (NPC), a highly invasive and metastatic head and neck malignancy, have not been
      made clear. In this study investigating these mechanisms, guanine nucleotide
      binding protein alpha(12) subunit (G(alpha)(12)) signaling was found by
      microarray analysis to be increased in primary NPC cells and NPC-derived cell
      lines. Using small interfering RNA to knock down G(alpha)(12) in NPC cells
      resulted in a reduction in cell migration and invasion as well as a reversal in
      fibroblastoid morphology. Using microarray analysis, we also found a reduction in
      expression of key actin dynamics regulators and several epithelial-to-mesenchymal
      transition-related genes in G(alpha)(12)-depleted NPC cells. Knocking down one of
      those genes, IQ motif containing GTPase activating protein 1, reduced the
      migration and formation of adherens junctions and reversed the fibroblastoid
      morphology of NPC cells, as knocking down G(alpha)(12) was found to do.
      Immunohistochemical analysis found NPC tumors to have significantly greater
      levels of G(alpha)(12) protein than the normal basal epithelial cells.
      Quantitative real-time PCR analysis revealed a significant correlation between
      G(alpha)(12) mRNA levels and NPC lymph node metastasis. Together, our findings
      support a model in which activation of G(alpha)(12) signaling promotes
      tumorigenesis and progression of NPC by modulating actin cytoskeleton
      reorganization and expression of epithelial-to-mesenchymal transition-related
      genes. =

PMID- 19602599
TI  - The limitations of routine total digoxin immunoassay in patients with advanced
      chronic kidney disease.

PMID- 19602600
TI  - Pharmacologic options to prevent postoperative ileus.
AB  - OBJECTIVE: To summarize the evidence on pharmacologic options in preventing
      postoperative ileus (POI). DATA SOURCES: The Cochrane Database of Reviews and
      OVID databases and Food and Drug Administration (FDA) Web site were searched
      (1950-April 2009) using the term postoperative ileus. STUDY SELECTION AND DATA
      EXTRACTION: Meta-analyses and randomized controlled trials were included for
      review. The FDA Web site was searched for clinical reviews and label information
      for drugs indicated for the prevention of POI. DATA SYNTHESIS: Three meta
      analyses, 2 on gum-chewing and 1 on alvimopan, and 18 clinical trials were
      identified. Only gum chewing and alvimopan were effective in preventing POI. Gum
      chewing reduced the time to first flatus and bowel movement (weighted mean
      difference 21h; p = 0.0006 and 33h; p = 0.0002, respectively). In one meta
      analysis, gum chewing significantly reduced length of stay (LOS) by 2.4 days (p <
      0.00001) but this was not replicated in the second meta-analysis. Alvimopan
      shortened the time to reach a composite endpoint of solid food intake, plus/minus
      flatus, and bowel movement (93 vs 105 h; p < 0.001). A higher incidence of
      myocardial infarction was observed in a 12-month study of alvimopan for the
      treatment of opioid-induced bowel dysfunction, but not in studies in patients
      undergoing bowel resection. Alvimopan decreased the time to written hospital
      discharge order (hazard ratio 1.35; p < 0.01), while the significance of a
      reduction in LOS (0.2-1.3 days) was not reported. CONCLUSIONS: Gum chewing and
      alvimopan are effective in preventing POI, but given safety concerns and higher
      cost with alvimopan, gum chewing may be preferred.

PMID- 19602601
TI  - Icodextrin metabolites in peritoneal dialysis.

PMID- 19602602
TI  - Analytical interferences in point-of-care testing glucometers by icodextrin and
      its metabolites: an overview.
AB  - Current point-of-care testing (POCT) glucometers are based on various test
      principles. Two major method groups dominate the market: glucose oxidase-based
      systems and glucose dehydrogenase-based systems using pyrroloquinoline quinone
      (GDH-PQQ) as a cofactor. The GDH-PQQ-based glucometers are replacing the older
      glucose oxidase-based systems because of their lower sensitivity for oxygen. On
      the other hand, the GDH-PQQ test method results in falsely elevated blood glucose
      levels in peritoneal dialysis patients receiving solutions containing icodextrin
      (e.g., Extraneal; Baxter, Brussels, Belgium). Icodextrin is metabolized in the
      systemic circulation into different glucose polymers, but mainly maltose, which
      interferes with the GDH-PQQ-based method. Clinicians should be aware of this
      analytical interference. The POCT glucometers based on the GDH-PQQ method should
      preferably not be used in this high-risk population and POCT glucose results
      inconsistent with clinical suspicion of hypoglycemic coma should be retested with
      another testing system.

PMID- 19602604
TI  - The use of the laparoscope for dialysis catheter implantation: valuable carry-on
      or excess baggage?

PMID- 19602603
TI  - Amino Acid-based peritoneal dialysis solutions for malnutrition: new
      perspectives.
AB  - Protein and energy malnutrition is frequently found in patients on maintenance
      dialysis and is associated with an increased risk of death. Among a variety of
      factors involved in the development of protein and energy malnutrition, such as
      acidosis, insulin resistance, inflammation, and dialysate protein losses,
      insufficient intake of proteins and energy as a result of anorexia plays a
      prominent role. Amino acid (AA)-based peritoneal dialysis (PD) solutions can
      induce an anabolic response in malnourished patients on continuous ambulatory PD
      if enough calories are ingested simultaneously. Poor appetite, however, may
      impede the intake of sufficient calories. Peritoneal dialysis solutions
      containing a mixture of AAs and glucose in a proper ratio can serve as a source
      of proteins and calories. Such a dialysis solution can be used in fasting
      patients on nocturnal automated PD as part of a regular dialysis schedule. Using
      a sophisticated technique involving stable isotopes, this dialysis mixture has
      been found to induce acute anabolic changes in whole body protein metabolism.
      Such a metabolic response is similar to that induced by food. Intraperitoneal
      AAs, in common with ingested proteins, can induce generation of hydrogen ions and
      urea through oxidation of specific AAs. Supplying AAs together with calories
      could bring about utilization of AAs for the synthesis of proteins rather than
      the oxidation of AAs, thereby limiting production of acid and urea. Using
      dialysis solutions with a buffer concentration of 40 mmol/L further contributes
      to maintaining acid-base homeostasis. We advocate consideration of usage of
      AA/glucose dialysate when PD patients cannot comply with dietary requirements. To
      evaluate the long-term effects of this approach on morbidity and mortality,
      clinical trials with large groups of patients are needed.

PMID- 19602605
TI  - Understanding the variability in ultrafiltration obtained with icodextrin.

PMID- 19602606
TI  - Novel approaches to prescribing icodextrin.

PMID- 19602607
TI  - The variability in ultrafiltration achieved with icodextrin, possibly explained.
AB  - BACKGROUND: A recent study by Jeloka et al. (Perit Dial Int 2006; 26:336-40)
      highlighted the high variability in maximum ultrafiltered volume (UF(max)) and
      the corresponding dwell time (t(max)) obtained using 7.5% icodextrin solution. We
      aimed to pinpoint the possible sources of this phenomenon by simulating the
      icodextrin ultrafiltration (UF) profiles according to the three-pore model of
      peritoneal transport. METHOD: The individual UF time courses observed in the
      study by Jeloka et al. (n = 29) were first characterized by linear and quadratic
      regression. We were then able to identify four main patterns. These were then
      adapted to UF profiles generated by the three-pore model by systematically
      altering the values of some model parameters, namely, the mass transfer area
      coefficient (MTAC or PS) for icodextrin/glucose, the peritoneal UF coefficient
      (LpS), the plasma colloid osmotic pressure gradient (DeltaPi), and the
      macromolecular clearance out of the peritoneal cavity (Cl(LF)). RESULTS:
      Modifications in the PS values caused only marginal variations in UF(max) and
      t(max), while more significant changes were produced by altering LpS and Cl(LF).
      However, far more evident was the importance of changes in DeltaPi. In fact,
      lowering DeltaPi to 14 mmHg caused a steady increase in UF with 10 - 14 hour
      dwells. On the contrary, the UF profiles became nearly "flat" when DeltaPi was
      increased to 30 mmHg. The parallel shifts induced by altering icodextrin
      metabolite concentrations did not markedly influence UF(max) or t(max).
      CONCLUSION: The UF pattern in icodextrin dwells seem to be mainly determined by
      the plasma colloid osmotic pressure, while only moderate changes can be seen with
      alterations in LpS and Cl(LF). The result is not completely unexpected
      considering that icodextrin acts by inducing a strong colloid osmotic gradient. A
      number of clinical studies would be needed, however, in order to prove this
      hypothesis.

PMID- 19602608
TI  - Icodextrin improves metabolic and fluid management in high and high-average
      transport diabetic patients.
AB  - BACKGROUND: Icodextrin-based solutions (ICO) have clinical and theoretical
      advantages over glucose-based solutions (GLU) in fluid and metabolic management
      of diabetic peritoneal dialysis (PD) patients; however, these advantages have not
      yet been tested in a randomized fashion. OBJECTIVE: To analyze the effects of ICO
      on metabolic and fluid control in high and high-average transport diabetic
      patients on continuous ambulatory PD (CAPD). PATIENTS AND METHODS: A 12-month,
      multicenter, open-label, randomized controlled trial was conducted to compare ICO
      (n = 30) versus GLU (n = 29) in diabetic CAPD patients with high-average and high
      peritoneal transport characteristics. The basic daily schedule was 3 x 2 L GLU
      (1.5%) and either 1 x 2 L ICO (7.5%) or 1 x 2 L GLU (2.5%) for the long-dwell
      exchange, with substitution of 2.5% or 4.25% for 1.5% GLU being allowed when
      clinically necessary. Variables related to metabolic and fluid control were
      measured each month. RESULTS: Groups were similar at baseline in all measured
      variables. More than 66% of the patients using GLU, but only 9% using ICO, needed
      prescriptions of higher glucose concentration solutions. Ultrafiltration (UF) was
      higher (198 +/- 101 mL/day, p < 0.05) in the ICO group than in the GLU group over
      time. Changes from baseline were more pronounced in the ICO group than in the GLU
      group for extracellular fluid volume (0.23 +/- 1.38 vs -1.0 +/- 1.48 L, p < 0.01)
      and blood pressure (systolic 1.5 +/- 24.0 vs -10.4 +/- 30.0 mmHg, p < 0.01;
      diastolic 1.5 +/- 13.5 vs -6.2 +/- 14.2 mmHg, p < 0.01). Compared to baseline,
      patients in the ICO group had better metabolic control than those in the GLU
      group: glucose absorption was more reduced (-17 +/- 44 vs -64 +/- 35 g/day) as
      were insulin needs (3.6 +/- 3.4 vs - 9.1 +/- 4.7 U/day, p < 0.01), fasting serum
      glucose (8.3 +/- 36.5 vs -37 +/- 25.8 mg/dL, p < 0.01), triglycerides (54.5 +/-
      31.9 vs -54.7 +/- 39.9 mg/dL, p < 0.01), and glycated hemoglobin (0.79% +/- 0.79%
      vs -0.98% +/- 0.51%, p < 0.01). Patients in the ICO group had fewer adverse
      events related to fluid and glucose control than patients in the GLU group.
      CONCLUSION: Icodextrin represents a significant advantage in the management of
      high transport diabetic patients on PD, improving peritoneal UF and fluid control
      and reducing the burden of glucose overexposure, thereby facilitating metabolic
      control.

PMID- 19602609
TI  - A combined crystalloid and colloid pd solution as a glucose-sparing strategy for
      volume control in high-transport apd patients: a prospective multicenter study.
AB  - BACKGROUND: Evidence is accumulating that the continuous exposure to high glucose
      concentrations during peritoneal dialysis (PD) is an important cause of
      ultrafiltration (UF) failure. The cornerstone of prevention and treatment of UF
      failure is reduction of glucose exposure, which will also alleviate the systemic
      impact of significant free glucose absorption. The challenge for the future is to
      discover new therapeutic strategies to enhance fluid and sodium removal while
      diminishing glucose load and exposure using combinations of available osmotic
      agents. OBJECTIVES: To investigate in patients on automated PD (APD) with a fast
      transport pattern whether there is a glucose-sparing advantage to replacing 7.5%
      icodextrin (ICO) during the long dwell with a mixed crystalloid and colloid PD
      fluid (bimodal UF) in an attempt to promote daytime UF and sodium removal while
      diminishing the glucose strength of the dialysate at night. DESIGN: A 2 parallel
      arm, 4 month, prospective nonrandomized study. SETTING: PD units or university
      hospitals in 4 French and Belgian districts. RESULTS: During the 4-month
      intervention period, net UF and peritoneal sodium removal during the long dwell
      when treated by bimodal UF was about 2-fold higher than baseline (with ICO). The
      estimated percent change (95% confidence interval) from baseline in net daytime
      UF for the bimodal solution was 150% (106% - 193%), versus 18% (-7% - 43%) for
      ICO (p < 0.001). The estimated percent change from baseline in peritoneal sodium
      removal for the bimodal solution was 147% (112% - 183%), versus 23% (-2% - 48%)
      for ICO (p < 0.001). The estimated percent change from baseline in UF efficiency
      (24-hour net UF divided by the amount of glucose absorbed) was significantly
      higher (p < 0.001) when using the bimodal solution was 71%, versus -5% for ICO.
      CONCLUSION: Prescription of bimodal UF during the day in APD patients offers the
      opportunity to optimize the long dwell exchange in a complete 24-hour APD cycle.
      The current study demonstrated that a bimodal solution based on the mixing of
      glucose (2.6%) and icodextrin (6.8%) achieved the double target of significantly
      improving UF and peritoneal sodium removal by exploring a new concept of glucose
      sparing PD therapy.

PMID- 19602610
TI  - Effects of twice-daily icodextrin administration on blood pressure and left
      ventricular mass in patients on continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Hypervolemia is a risk factor for left ventricular hypertrophy and
      hypertension in peritoneal dialysis patients. Icodextrin improves volume control
      by increasing ultrafiltration in peritoneal dialysis patients. AIM: To examine
      the effects of twice-daily icodextrin administration on blood pressure and left
      ventricular hypertrophy in peritoneal dialysis patients with hypervolemia and
      ultrafiltration failure. METHOD AND RESULTS: Administration of icodextrin twice
      daily resulted in a significant reduction in the left ventricular mass index
      (LVMI) of patients by the end of the third month (p < 0.05). The reduction in
      LVMI was also significant for the once-daily icodextrin group (p < 0.05). Mean
      blood pressure of patients receiving icodextrin twice daily was significantly
      reduced (p < 0.05). By the end of the third month no significant changes were
      observed in mean blood pressure of the patients using once-daily icodextrin (p >
      0.05). No statistically significant changes were observed in weekly total
      creatinine clearances or Kt/V of patients in either group at the end of 3 months
      (NS). CONCLUSION: Twice-daily icodextrin administration was clinically beneficial
      as shown by reduced blood pressure and prevention of the progress of left
      ventricular hypertrophy without causing any decrease in dialysis adequacy or any
      side effects. The icodextrin metabolite results did not suggest any further
      increase in their values when comparing once- to twice-daily administration of
      icodextrin. Although prescription of icodextrin once daily may yield good
      clinical results in the long term, this study showed that it may be more
      efficient to use twice-daily icodextrin for at least a specific period for the
      purpose of obtaining quicker results in patients with ultrafiltration failure,
      serious hypervolemia, or hard-to-control blood pressure conditions.

PMID- 19602611
TI  - Seven-year follow-up of peritoneal dialysis patients in Taiwan.
AB  - BACKGROUND: There are no Taiwanese publications and only a few Asian publications
      on the long-term outcome of peritoneal dialysis (PD) patients. The aim of this
      study was to evaluate the outcome of PD patients in Taiwan during a 7-year follow
      up period. PATIENTS AND METHODS: This study enrolled 67 patients (23 males, mean
      age 46.2 +/- 14.5 years) on maintenance PD. We administered the Short-Form
      questionnaire on 30 September 1998 and recorded major events and outcomes until
      30 September 2005. We compared differences in initial parameters between groups
      categorized by PD patient survival and PD technique survival. Causes of mortality
      and transfer to hemodialysis were determined. PD patient and PD technique
      survival rates were measured and risk factors for patient mortality and PD
      technique failure were analyzed. RESULTS: Those in patient survival or PD
      technique survival groups had lower mean age (p < 0.001 and 0.018 respectively)
      and higher serum albumin level (p = 0.015 and 0.041 respectively) compared to
      those that died or failed PD. The 7-year patient survival rate was 77% and the PD
      technique survival rate was 58%. The independent predictors for PD technique
      failure included lower Mental Component Summary scores [hazard ratio (HR) = 0.85,
      p = 0.031] and diabetes mellitus (HR = 4.63, p < 0.001), whereas lower serum
      albumin level (HR = 0.22, p = 0.031), lower Physical Component Summary scores (HR
      = 0.67, p = 0.047), and presence of diabetes mellitus (HR = 5.123, p = 0.009)
      were the independent predictors for patient mortality. CONCLUSION: For our PD
      patients, both patient and technique survival rates are good. Better glycemic
      control, adequate nutrition, and enhancement of health-related quality of life
      are all of potential prognostic benefit.

PMID- 19602612
TI  - Skin color is associated with insulin resistance in nondiabetic peritoneal
      dialysis patients.
AB  - BACKGROUND: Changes in skin color are common among dialysis patients. They are
      associated with urochrome pigments, hemoglobin, and changes in cutaneous
      vasculature. Insulin resistance (IR) is strongly linked to cutaneous vascular
      dysfunction and is prevalent in dialysis patients. We postulated skin color may
      be associated with IR in dialysis patients because of the alternation in
      cutaneous vasculature. METHODS: 50 nondiabetic peritoneal dialysis (PD) patients
      were recruited for measurements of skin color by the Commission Internationale de
      I'Eclairage (CIE; International Commission on Illumination) system ("L" "a" "b"
      system). The "L" values represent skin brightness, "a" redness, and "b"
      yellowness. Correlation analysis between skin color, homeostatic model assessment
      (HOMA(IR)), high-density lipoprotein cholesterol (HDL-C), and adiponectin was
      performed. RESULTS: We divided patients (age 45 +/- 13 years, 31 women) into 3
      groups according to tertiles of HOMA(IR). Patients with higher HOMA(IR) had a
      trend to have poor skin color (lower "a" and "b" values; p = 0.038 and 0.064).
      HOMA(IR), adiponectin, and HDL-C levels were correlated with "a" and "b" values
      in logarithm (all p < 0.05). After adjustments for age, hemoglobin level,
      duration of PD, and residual renal glomerular filtration rate, only HOMA(IR) was
      associated with "a" values (p = 0.038) and HDL-C was associated with "b" values
      (p = 0.048) in logarithm. CONCLUSIONS: Skin color, measured noninvasively, is
      associated with HOMA(IR) and HDL-C. Nondiabetic PD patients that had more severe
      IR had worse skin color.

PMID- 19602613
TI  - Dialytic phosphate removal: a modifiable measure of dialysis efficacy in
      automated peritoneal dialysis.
AB  - BACKGROUND: Although hyperphosphatemia is one of the few established risk factors
      for cardiovascular mortality in patients on dialysis, the relationship between
      peritoneal dialysis (PD) prescription and dialytic phosphate removal is largely
      unexplored. METHODS AND PATIENTS: We analyzed 24-hour clearances (n = 60)
      together with peritoneal equilibration tests (PETs) (n = 52) performed in
      children and adolescents (n = 35) on automated PD. RESULTS: Dialytic phosphate
      clearance was more closely correlated with 2-hour and 4-hour dialysate-to-plasma
      ratio (D/P) of phosphate in the PETs (r = 0.44 and r = 0.52, both p < 0.0001)
      than with 2-hour and 4-hour D/P creatinine (r = 0.26 and r = 0.27, both p <
      0.05). Dialytic 24-hour phosphate clearance was independently predicted by total
      fluid turnover (partial R(2) = 0.48, p < 0.001), the number of cycles (r = 0.52,
      p < 0.001), 2-hour D/P phosphate (partial R(2) = 0.07, p = 0.001), dwell time
      (partial R(2) = 0.05, p = 0.01), and achieved ultrafiltration (partial R(2) =
      0.05, p = 0.005). 4-hour D/P phosphate and 24-hour phosphate clearance were
      significantly lower in hyperphosphatemic children (3.38 +/- 1.17 vs 4.56 +/- 1.99
      L/1.73 m(2)/day, p < 0.05), whereas creatinine equilibration and clearance rates
      were not distinctive. CONCLUSION: Dialytic phosphate removal is an important
      modifiable determinant of phosphate control in automated PD. It strongly depends
      on total dialysate turnover and the prescribed number of cycles and is more
      adequately predicted by phosphate than by creatinine equilibration
      characteristics. Due to the deleterious effects of hyperphosphatemia, dialytic
      phosphate removal should be monitored routinely.

PMID- 19602614
TI  - Oral health and inflammation in patients with end-stage renal failure.
AB  - BACKGROUND/AIMS: End-stage renal disease (ESRD) patients have an increased risk
      of atherosclerotic complications. In both hemodialysis (HD) patients and the
      general population, it has become evident that inflammation plays an important
      role in the pathogenesis of atherosclerotic complications. Oral and dental
      problems in ESRD patients could be an important source of inflammation, thus
      treatment of these problems is important to protect these patients from potential
      infections. The decayed, missing, and filled teeth (DMFT) index is an indicator
      of oral and dental health status. Our aim was to analyze and compare salivary
      flow rate (SFR), salivary pH (SpH), salivary buffering capacity (SBC), and DMFT
      index and plaque index (PI) values in PD patients to HD patients and healthy
      controls (C) and establish the relationship between these parameters and C
      reactive protein (CRP). METHODS: 76 PD patients, 100 HD patients, and 111 Cs were
      included in the study. SFR (milliliters/minute) was measured in stimulated whole
      saliva, SpH was measured using the Merck indicator, and SBC was measured
      according to the method of Ericsson: 1 mL whole saliva was added to 3 mL 0.005 N
      HCl and a stream of air was passed through this mixture for 20 minutes. Finally,
      DMFT index and PI values were calculated. RESULTS: No statistically significant
      differences were found in age or gender distribution among PD, HD, and C groups.
      There was also no significant difference in time on dialysis between PD and HD
      groups. SFR was significantly lower in the PD and HD groups than in the C group
      (1.30 +/- 0.83 and 0.70 +/- 0.32 vs 1.64 +/- 0.45 mL/min) and lower in the HD
      than in the PD group (p < 0.001). SpH (8.35 +/- 0.43 and 8.12 +/- 0.74 vs 7.16 +/
      0.76) and SBC (7.39 +/- 0.47 and 6.82 +/- 0.70 vs 5.08 +/- 0.73) were
      significantly higher in the PD and HD groups than in the C group and higher in
      the PD than in the HD group (p < 0.05 and p < 0.001 respectively). The numbers of
      filled teeth were significantly higher in the PD than in the HD and C groups (p <
      0.001). DMFT index was significantly higher in the PD than in the HD group (p <
      0.001). Finally, PI values were significantly higher in the PD and HD groups than
      in the C group (p < 0.001) and higher in the HD than in the PD group, although
      this was not statistically significant. In the present study, we also found
      higher CRP values in HD than in PD patients and a positive correlation between
      CRP and PI values in PD patients. CONCLUSIONS: PD patients have higher SFR, SpH,
      and SBC values than HD patients; however, higher DMFT index and higher numbers of
      filled teeth were observed in PD patients. Compared to healthy controls, patients
      on dialysis had worse dental and periodontal findings, which might have a role in
      microinflammation in this group of patients.

PMID- 19602615
TI  - Remembrances of Barbara Prowant by her fellow ISPD nurses around the world.

PMID- 19602616
TI  - A rare cause of peritoneal dialysis-related peritonitis: Gemella haemolysans.

PMID- 19602617
TI  - Metabolic phenotyping of a model of adipocyte differentiation.
AB  - The 3T3-L1 murine cell line is a robust and widely used model for the study of
      adipogenesis and processes occurring in mature adipocytes. The fibroblastic like
      cells can be induced by hormones to differentiate into mature adipocytes. In this
      study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell
      line has been studied using gas chromatography-mass spectrometry, (1)H nuclear
      magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct
      infusion-mass spectrometry, and 13C substrate labeling in conjunction with
      multivariate statistics. The changes in metabolite concentrations at distinct
      periods during differentiation have been defined including alterations in the TCA
      cycle, glycolysis, the production of odd chain fatty acids by alpha-oxidation,
      fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans
      esterification to produce complex lipids. The metabolic changes induced during
      differentiation of the 3T3-L1 cell line were then compared with the metabolic
      differences between pre- and postdifferentiation primary adipocytes. These
      metabolic alterations reflect the changing role of the 3T3-L1 cells during
      differentiation, as well as possibly providing metabolic triggers to stimulate
      the processes which occur during differentiation.

PMID- 19602618
TI  - Transcriptional changes in right ventricular tissues are enriched in the outflow
      tract compared with the apex during chronic pulmonary embolism in rats.
AB  - Moderate to severe pulmonary embolism (PE) can cause pulmonary arterial
      hypertension and right ventricular (RV) heart damage. Previous studies from our
      laboratory indicate that the basal outflow tract of the RV is injured and has
      acute inflammation followed by tissue remodeling while the apex appears normal.
      The present studies examine transcription responses to chronic PE in RV apex and
      outflow tracts using DNA microarrays to identify transcription responses by
      region. Changes predominated in the RV outflow tract (8,575 genes showed >/=1.5
      fold expression change). Gene ontology and KEGG analyses indicated a significant
      decrease in genes involved in cellular respiration and energy metabolism and
      increases in inflammatory cell adhesion molecules and extracellular matrix
      proteins. Signal pathways for wound healing such as fibroblast growth factor,
      collagen synthesis, and CCN proteins (named for the first three members of the
      family: cysteine-rich protein 61, connective tissue growth factor, and
      nephroblastoma overexpressed gene) were strongly upregulated. In comparison, few
      genes (422) showed significant change in the RV apex tissue. Apex-selective genes
      included two genes affecting metabolism and a stretch-sensitive transcription
      factor (ankyrin repeat domain 1). We conclude that the RV outflow tract is
      subject to strong proinflammatory and profibrotic remodeling transcriptional
      responses in chronic PE. Severe loss of genes involved in cellular respiration is
      consistent with previous histology indicating a shift in cell types present
      within the outflow tract tissue away from highly energy-dependant cardiomyocytes
      to less metabolically active cells during remodeling. The apex region of the RV
      had few compensating adaptations.

PMID- 19602619
TI  - Flipping the centromere switch: reactivation of a dormant centromere in maize.

PMID- 19602620
TI  - Targeted overexpression of a sodium transporter in the root stele increases
      salinity tolerance.

PMID- 19602622
TI  - Reactivation of an inactive centromere reveals epigenetic and structural
      components for centromere specification in maize.
AB  - Stable maize (Zea mays) chromosomes were recovered from an unstable dicentric
      containing large and small versions of the B chromosome centromere. In the stable
      chromosome, the smaller centromere had become inactivated. This inactive
      centromere can be inherited from one generation to the next attached to the
      active version and loses all known cytological and molecular properties of active
      centromeres. When separated from the active centromere by intrachromosomal
      recombination, the inactive centromere can be reactivated. The reactivated
      centromere regains the molecular attributes of activity in anaphase I of meiosis.
      When two copies of the dicentric chromosome with one active and one inactive
      centromere are present, homologous chromosome pairing reduces the frequency of
      intrachromosomal recombination and thus decreases, but does not eliminate, the
      reactivation of inactive centromeres. These findings indicate an epigenetic
      component to centromere specification in that centromere inactivation can be
      directed by joining two centromeres in opposition. These findings also indicate a
      structural aspect to centromere specification revealed by the gain of activity at
      the site of the previously inactive sequences.

PMID- 19602621
TI  - Aberrant mRNA transcripts and the nonsense-mediated decay proteins UPF2 and UPF3
      are enriched in the Arabidopsis nucleolus.
AB  - The eukaryotic nucleolus is multifunctional and involved in the metabolism and
      assembly of many different RNAs and ribonucleoprotein particles as well as in
      cellular functions, such as cell division and transcriptional silencing in
      plants. We previously showed that Arabidopsis thaliana exon junction complex
      proteins associate with the nucleolus, suggesting a role for the nucleolus in
      mRNA production. Here, we report that the plant nucleolus contains mRNAs,
      including fully spliced, aberrantly spliced, and single exon gene transcripts.
      Aberrant mRNAs are much more abundant in nucleolar fractions, while fully spliced
      products are more abundant in nucleoplasmic fractions. The majority of the
      aberrant transcripts contain premature termination codons and have
      characteristics of nonsense-mediated decay (NMD) substrates. A direct link
      between NMD and the nucleolus is shown by increased levels of the same aberrant
      transcripts in both the nucleolus and in Up-frameshift (upf) mutants impaired in
      NMD. In addition, the NMD factors UPF3 and UPF2 localize to the nucleolus,
      suggesting that the Arabidopsis nucleolus is therefore involved in identifying
      aberrant mRNAs and NMD.

PMID- 19602623
TI  - Arabidopsis tRNA adenosine deaminase arginine edits the wobble nucleotide of
      chloroplast tRNAArg(ACG) and is essential for efficient chloroplast translation.
AB  - RNA editing changes the coding/decoding information relayed by transcripts via
      nucleotide insertion, deletion, or conversion. Editing of tRNA anticodons by
      deamination of adenine to inosine is used both by eukaryotes and prokaryotes to
      expand the decoding capacity of individual tRNAs. This limits the number of tRNA
      species required for codon-anticodon recognition. We have identified the
      Arabidopsis thaliana gene that codes for tRNA adenosine deaminase arginine
      (TADA), a chloroplast tRNA editing protein specifically required for deamination
      of chloroplast (cp)-tRNAArg(ACG) to cp-tRNAArg(ICG). Land plant TADAs have a C
      terminal domain similar in sequence and predicted structure to prokaryotic tRNA
      deaminases and also have very long N-terminal extensions of unknown origin and
      function. Biochemical and mutant complementation studies showed that the C
      terminal domain is sufficient for cognate tRNA deamination both in vitro and in
      planta. Disruption of TADA has profound effects on chloroplast translation
      efficiency, leading to reduced yields of chloroplast-encoded proteins and
      impaired photosynthetic function. By contrast, chloroplast transcripts accumulate
      to levels significantly above those of wild-type plants. Nevertheless, absence of
      cp-tRNAArg(ICG) is compatible with plant survival, implying that two out of three
      CGN codon recognition occurs in chloroplasts, though this mechanism is less
      efficient than wobble pairing.

PMID- 19602624
TI  - Sieve element Ca2+ channels as relay stations between remote stimuli and sieve
      tube occlusion in Vicia faba.
AB  - Damage induces remote occlusion of sieve tubes in Vicia faba by forisome
      dispersion, triggered during the passage of an electropotential wave (EPW). This
      study addresses the role of Ca2+ channels and cytosolic Ca2+ elevation as a link
      between EPWs and forisome dispersion. Ca2+ channel antagonists affect the initial
      phase of the EPW as well as the prolonged plateau phase. Resting levels of sieve
      tube Ca2+ of approximately 50 nM were independently estimated using Ca2+
      selective electrodes and a Ca2+-sensitive dye. Transient changes in cytosolic
      Ca2+ were observed in phloem tissue in response to remote stimuli and showed
      profiles similar to those of EPWs. The measured elevation of Ca2+ in sieve tubes
      was below the threshold necessary for forisome dispersion. Therefore, forisomes
      need to be associated with Ca2+ release sites. We found an association between
      forisomes and endoplasmic reticulum (ER) at sieve plates and pore-plasmodesma
      units where high-affinity binding of a fluorescent Ca2+ channel blocker mapped an
      increased density of Ca2+ channels. In conclusion, propagation of EPWs in
      response to remote stimuli is linked to forisome dispersion through transiently
      high levels of parietal Ca2+, release of which depends on both plasma membrane
      and ER Ca2+ channels.

PMID- 19602626
TI  - Comparative analysis between homoeologous genome segments of Brassica napus and
      its progenitor species reveals extensive sequence-level divergence.
AB  - Homoeologous regions of Brassica genomes were analyzed at the sequence level.
      These represent segments of the Brassica A genome as found in Brassica rapa and
      Brassica napus and the corresponding segments of the Brassica C genome as found
      in Brassica oleracea and B. napus. Analysis of synonymous base substitution rates
      within modeled genes revealed a relatively broad range of times (0.12 to 1.37
      million years ago) since the divergence of orthologous genome segments as
      represented in B. napus and the diploid species. Similar, and consistent, ranges
      were also identified for single nucleotide polymorphism and insertion-deletion
      variation. Genes conserved across the Brassica genomes and the homoeologous
      segments of the genome of Arabidopsis thaliana showed almost perfect
      collinearity. Numerous examples of apparent transduplication of gene fragments,
      as previously reported in B. oleracea, were observed in B. rapa and B. napus,
      indicating that this phenomenon is widespread in Brassica species. In the
      majority of the regions studied, the C genome segments were expanded in size
      relative to their A genome counterparts. The considerable variation that we
      observed, even between the different versions of the same Brassica genome, for
      gene fragments and annotated putative genes suggest that the concept of the pan
      genome might be particularly appropriate when considering Brassica genomes.

PMID- 19602627
TI  - Vasomotion and insulin-mediated capillary recruitment--part of the explanation?

PMID- 19602625
TI  - Two seven-transmembrane domain MILDEW RESISTANCE LOCUS O proteins cofunction in
      Arabidopsis root thigmomorphogenesis.
AB  - Directional root expansion is governed by nutrient gradients, positive
      gravitropism and hydrotropism, negative phototropism and thigmotropism, as well
      as endogenous oscillations in the growth trajectory (circumnutation). Null
      mutations in phylogenetically related Arabidopsis thaliana genes MILDEW
      RESISTANCE LOCUS O 4 (MLO4) and MLO11, encoding heptahelical, plasma membrane
      localized proteins predominantly expressed in the root tip, result in aberrant
      root thigmomorphogenesis. mlo4 and mlo11 mutant plants show anisotropic, chiral
      root expansion manifesting as tightly curled root patterns upon contact with
      solid surfaces. The defect in mlo4 and mlo11 mutants is nonadditive and dependent
      on light and nutrients. Genetic epistasis experiments demonstrate that the mutant
      phenotype is independently modulated by the Gbeta subunit of the heterotrimeric G
      protein complex. Analysis of expressed chimeric MLO4/MLO2 proteins revealed that
      the C-terminal domain of MLO4 is necessary but not sufficient for MLO4 action in
      root thigmomorphogenesis. The expression of the auxin efflux carrier fusion, PIN1
      green fluorescent protein, the pattern of auxin-induced gene expression, and
      acropetal as well as basipetal auxin transport are altered at the root tip of
      mlo4 mutant seedlings. Moreover, addition of auxin transport inhibitors or the
      loss of EIR1/AGR1/PIN2 function abolishes root curling of mlo4, mlo11, and wild
      type seedlings. These results demonstrate that the exaggerated root curling
      phenotypes of the mlo4 and mlo11 mutants depend on auxin gradients and suggest
      that MLO4 and MLO11 cofunction as modulators of touch-induced root tropism.

PMID- 19602628
TI  - Duodenal epithelial cells provide a stimulus package for the recovery from an
      acid load.

PMID- 19602629
TI  - A large slice of cardiac output or humble pie for the respiratory muscles?

PMID- 19602630
TI  - Regulation of smooth muscle contraction/relaxation: paradigm shifts and
      quantifying arrows.

PMID- 19602631
TI  - Phosphatidic acid: a novel mechanical mechanism for how resistance exercise
      activates mTORC1 signalling.

PMID- 19602632
TI  - Sensing the fullness of the bladder.

PMID- 19602633
TI  - The influence of thermal factors on post-exercise haemodynamics in endurance
      exercise-trained men.

PMID- 19602634
TI  - Opioid-induced suppression of genioglossal muscle activity: is it clinically
      important?

PMID- 19602635
TI  - Maternal nutritional history predicts obesity in adult offspring independent of
      postnatal diet.

PMID- 19602636
TI  - The impact of maternal high fat nutrition on the next generation: food for
      thought?

PMID- 19602637
TI  - Mitochondrial biogenesis in adipose tissue: can exercise make fat cells 'fit'?

PMID- 19602638
TI  - Instrumenting the health care enterprise for discovery research in the genomic
      era.
AB  - Tens of thousands of subjects may be required to obtain reliable evidence
      relating disease characteristics to the weak effects typically reported from
      common genetic variants. The costs of assembling, phenotyping, and studying these
      large populations are substantial, recently estimated at three billion dollars
      for 500,000 individuals. They are also decade-long efforts. We hypothesized that
      automation and analytic tools can repurpose the informational byproducts of
      routine clinical care, bringing sample acquisition and phenotyping to the same
      high-throughput pace and commodity price-point as is currently true of genome
      wide genotyping. Described here is a demonstration of the capability to acquire
      samples and data from densely phenotyped and genotyped individuals in the tens of
      thousands for common diseases (e.g., in a 1-yr period: N = 15,798 for rheumatoid
      arthritis; N = 42,238 for asthma; N = 34,535 for major depressive disorder) in
      one academic health center at an order of magnitude lower cost. Even for rare
      diseases caused by rare, highly penetrant mutations such as Huntington disease (N
      = 102) and autism (N = 756), these capabilities are also of interest.

PMID- 19602639
TI  - Identification of deleterious mutations within three human genomes.
AB  - Each human carries a large number of deleterious mutations. Together, these
      mutations make a significant contribution to human disease. Identification of
      deleterious mutations within individual genome sequences could substantially
      impact an individual's health through personalized prevention and treatment of
      disease. Yet, distinguishing deleterious mutations from the massive number of
      nonfunctional variants that occur within a single genome is a considerable
      challenge. Using a comparative genomics data set of 32 vertebrate species we show
      that a likelihood ratio test (LRT) can accurately identify a subset of
      deleterious mutations that disrupt highly conserved amino acids within protein
      coding sequences, which are likely to be unconditionally deleterious. The LRT is
      also able to identify known human disease alleles and performs as well as two
      commonly used heuristic methods, SIFT and PolyPhen. Application of the LRT to
      three human genomes reveals 796-837 deleterious mutations per individual,
      approximately 40% of which are estimated to be at <5% allele frequency. However,
      the overlap between predictions made by the LRT, SIFT, and PolyPhen, is low; 76%
      of predictions are unique to one of the three methods, and only 5% of predictions
      are shared across all three methods. Our results indicate that only a small
      subset of deleterious mutations can be reliably identified, but that this subset
      provides the raw material for personalized medicine.

PMID- 19602641
TI  - Evidence-based medicine among Jordanian family physicians: awareness, attitude,
      and knowledge.
AB  - OBJECTIVE: To assess family practitioners' attitudes toward and awareness of
      evidence-based medicine (EBM). DESIGN: A cross-sectional study from a
      questionnaire distributed between January and March 2007. SETTING: Rural and
      urban family medicine centres throughout Jordan that are affiliated with the
      Ministry of Health, military centres, university medical centres, and the private
      sector. PARTICIPANTS: Two hundred family physicians. MAIN OUTCOME MEASURES:
      Family physicians' attitudes toward EBM; training in EBM; barriers to practising
      EBM; level of awareness of and access to EBM journals and databases; and
      knowledge and understanding of related technical terms. RESULTS: The response
      rate was 70.5%. Among those who responded, 56.7% were women and 42.6% were
      between the ages of 40 and 49 years. More than 50% of the respondents were
      working in mixed urban and rural practice settings. Most of the respondents had a
      positive attitude toward EBM: 63.5% welcomed the concept of EBM; more than 40%
      used EBM in their daily practices; and 90% agreed that practising EBM improved
      patient care. Of the respondents, 42.6% thought that the best way to move from
      opinion-based medicine to EBM was through learning the skills of EBM. Fifty
      percent of the respondents had access to MEDLINE, while only 20.4% of them had
      received formal training in research and critical appraisal. Lack of personal
      time was the main perceived barrier to practising EBM. Participants reported a
      low level of awareness of some of the technical terms. CONCLUSION: Jordanian
      family physicians showed eagerness to learn and implement EBM in their daily
      practices. Nevertheless, they need more guidance and training to ensure the
      correct application of EBM ideals.

PMID- 19602640
TI  - The ClinSeq Project: piloting large-scale genome sequencing for research in
      genomic medicine.
AB  - ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a
      tool for clinical research. By piloting the acquisition of large amounts of DNA
      sequence data from individual human subjects, we are fostering the development of
      hypothesis-generating approaches for performing research in genomic medicine,
      including the exploration of issues related to the genetic architecture of
      disease, implementation of genomic technology, informed consent, disclosure of
      genetic information, and archiving, analyzing, and displaying sequence data. In
      the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the
      evaluation of each includes obtaining a detailed family and medical history, as
      well as a clinical evaluation. The participants are being consented broadly for
      research on many traits and for whole-genome sequencing. Initially, Sanger-based
      sequencing of 300-400 genes thought to be relevant to atherosclerosis is being
      performed, with the resulting data analyzed for rare, high-penetrance variants
      associated with specific clinical traits. The participants are also being
      consented to allow the contact of family members for additional studies of
      sequence variants to explore their potential association with specific
      phenotypes. Here, we present the general considerations in designing ClinSeq,
      preliminary results based on the generation of an initial 826 Mb of sequence
      data, the findings for several genes that serve as positive controls for the
      project, and our views about the potential implications of ClinSeq. The early
      experiences with ClinSeq illustrate how large-scale medical sequencing can be a
      practical, productive, and critical component of research in genomic medicine.

PMID- 19602642
TI  - Hypertension and the family physician.

PMID- 19602646
TI  - More than the diagnosis.

PMID- 19602644
TI  - Hypertension management by family physicians: is it time to pat ourselves on the
      back?

PMID- 19602648
TI  - Congratulations CFP and VAC!

PMID- 19602649
TI  - [Thank you].

PMID- 19602650
TI  - Addressing metformin.

PMID- 19602651
TI  - Far-infrared saunas for treatment of cardiovascular risk factors: summary of
      published evidence.
AB  - OBJECTIVE: To review the literature about the health benefits of far-infrared
      sauna (FIRS) use. QUALITY OF EVIDENCE: A search of Web of Science, EBSCO, Ovid
      MEDLINE, Ovid HealthSTAR, and EMBASE using the terms far-infrared and sauna,
      refined by limiting the search to studies of humans published in English, yielded
      9 relevant papers (level I or level II evidence). MAIN MESSAGE: Far-infrared
      saunas are approved by the Canadian Standards Association and are sold to the
      public. The manufacturers claim numerous health benefits; however, the published
      evidence to substantiate these claims is limited. Four papers support the use of
      FIRS therapy for those with congestive heart failure and 5 papers support its use
      for those with coronary risk factors. CONCLUSION: There is limited moderate
      evidence supporting FIRS efficacy in normalizing blood pressure and treating
      congestive heart failure; fair evidence, from a single study, supporting FIRS
      therapy in chronic pain; weak evidence, from a single study, supporting FIRS
      therapy in chronic fatigue syndrome; weak evidence, from a single study,
      supporting FIRS therapy for obesity; and consistent fair evidence to refute
      claims regarding the role of FIRSs in cholesterol reduction.

PMID- 19602652
TI  - 2009 Canadian Hypertension Education Program recommendations: an annual update.

PMID- 19602653
TI  - Hyperthyroidism during pregnancy.
AB  - QUESTION: I have a 33-year-old patient with hyperthyroidism who is 6 weeks
      pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole
      3 times daily. She was initially treated with propylthiouracil but was switched
      to methimazole owing to urticaria. I have heard about birth defects in infants
      whose mothers used methimazole during pregnancy. How safe is it? ANSWER: In North
      America, propylthiouracil has been the drug of choice for hyperthyroidism during
      pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is
      an alternative for patients who cannot tolerate propylthiouracil. Some case
      reports raised concern about fetal toxicity from methimazole, which is reportedly
      characterized by aplasia cutis, esophageal atresia, choanal atresia, facial
      abnormalities, and mental retardation. However, causality is unclear and the
      overall risk of congenital abnormalities in infants exposed to methimazole in
      utero was not higher than in those exposed to nonteratogenic drugs in cohort
      studies. It is important for a pregnant woman to continue methimazole, if
      necessary, because uncontrolled hyperthyroidism increases the risk of
      complications such as preterm labour and low birth weight.

PMID- 19602654
TI  - Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric
      patients.
AB  - QUESTION: Children frequently present to my rural emergency department with
      asthma exacerbations. Should I prescribe systemic corticosteroids? If so, which
      systemic corticosteroid should I prescribe? ANSWER: A short course of steroids is
      indicated in the treatment of asthma exacerbations. Both prednisone (1 to 2 mg/kg
      daily for 5 days) and dexamethasone (0.3 to 0.6 mg/kg daily for 1 to 5 days) are
      effective in reducing hospital admissions and unscheduled return to care, with
      minimal side effects.

PMID- 19602655
TI  - A shocking episode: care of electrical injuries.

PMID- 19602656
TI  - Genetics: prostate cancer.

PMID- 19602657
TI  - Question: Can you identify this condition? Cutaneous lymphoid hyperplasia.

PMID- 19602658
TI  - Question: Can you identify this condition? Lichen sclerosus.

PMID- 19602659
TI  - Question: Can you identify this condition? Pemphigus vulgaris.

PMID- 19602660
TI  - Question: Can you identify this condition? Gianotti-Crosti syndrome.

PMID- 19602661
TI  - Family physicians offering dermatologic services.

PMID- 19602662
TI  - Comparison of primary care physician payment models in the management of
      hypertension.
AB  - OBJECTIVE: To determine primary care physician screening, treatment, and control
      rates for hypertension and to examine whether type of physician payment model
      affected these rates. DESIGN: A cross-sectional chart abstraction study. SETTING:
      Community health centres (salary), primary care networks (capitation), or
      traditional fee-for-service practices in Ontario. PARTICIPANTS: A total of 135
      primary care physicians, 45 from each of the 3 different models of care. Data
      were abstracted from 28 adult patient charts randomly selected from each
      physician. MAIN OUTCOME MEASURES: Screening rates were based on the presence of
      at least 1 blood pressure reading in the past 3 years, treatment rates on the
      number of patients with hypertension treated with antihypertensive medication,
      and control rates on the number of patients with hypertension whose most recent
      blood pressure readings were below 140/90 mm Hg, below 130/80 mm Hg for patients
      with diabetes, or below 120/75 mm Hg for patients with renal disease. RESULTS:
      Overall, 92.5% of all patients were screened for hypertension, 86.4% of patients
      with hypertension were treated with antihypertensive medications, and 44.9% of
      patients with hypertension had their blood pressure controlled. Mean screening
      rates were 90.6%, 93.5%, and 93.3% (P = .22), and after adjusting for
      sociodemographic factors and comorbid conditions, mean treatment rates were
      90.9%, 81.0%, and 87.4% (P < .05) and mean control rates were 54.5%, 38.6%, and
      41.6% (P < .05) for capitation, salary, and fee-for-service physicians,
      respectively. CONCLUSION: Our results showed that although screening rates were
      similar between all 3 models, there were differences in treatment and control
      rates, with capitation physicians having the best treatment and control rates.
      Further investigation into whether this type of payment model results in improved
      chronic disease management for other chronic diseases and preventative care
      maneuvers will give support to health care policy makers who are moving toward
      capitation-type payment models for primary care delivery.

PMID- 19602664
TI  - Hypertension treatment and control rates: chart review in an academic family
      medicine clinic.
AB  - OBJECTIVE: To characterize hypertension management in an academic family medicine
      clinic. DESIGN: Cross-sectional chart review. SETTING: Academic family medicine
      clinic in Edmonton, Alta. PARTICIPANTS: A total of 210 patients with 1 or more
      visits for hypertension during the previous 3 years. MAIN OUTCOME MEASURES:
      Patient characteristics, current antihypertensive therapies, most recent blood
      pressure measurements, and compelling indications according to the 2006 Canadian
      Hypertension Education Program recommendations. RESULTS: A total of 185 subjects
      (88%) were prescribed antihypertensive medications, and 89 (42%) had controlled
      hypertension. Younger subjects, people with diabetes, and people not receiving
      antihypertensive medication therapy appeared less likely to have controlled
      hypertension. There were 76 subjects (36%) prescribed 1 antihypertensive
      medication, 65 subjects (31%) prescribed 2 antihypertensive medications, and 44
      (21%) prescribed 3 or more antihypertensive medications. Angiotensin-converting
      enzyme inhibitors were prescribed for 51% of the subjects, diuretics for 47%,
      beta-blockers for 27%, calcium channel blockers for 23%, angiotensin receptor
      blockers for 20%, and alpha-blockers for 1%. CONCLUSION: Hypertension treatment
      and control rates in this academic family medicine clinic appear to be better
      than those in the general population. Following the principles of a continuous
      quality improvement process, this information will serve as an important
      foundation for identifying areas to improve hypertension management in the
      clinic.

PMID- 19602663
TI  - Drug management for hypertension in type 2 diabetes in family practice.
AB  - OBJECTIVE: To describe the number and classes of antihypertensive medications
      prescribed to patients with type 2 diabetes in community family practices, and to
      estimate the aggressiveness or "dosage intensity" of prescribing for hypertension
      in these situations. DESIGN: Practice-based, cross-sectional observational study.
      SETTING: Seventeen rural and urban family practices in the Maritime Family
      Practice Research Network in Nova Scotia, New Brunswick, and Prince Edward
      Island. PARTICIPANTS: A total of 670 patients with type 2 diabetes, ranging from
      25 to 92 years of age. MAIN OUTCOME MEASURES: Number, classes, and combinations
      of classes of antihypertensive medications prescribed, as well as an index of
      each medication's dosage intensity. RESULTS: Almost 80% of patients studied had
      hypertension. Participants with hypertension were taking an average of 2.5
      medications, and 47.6% were taking 3 or more antihypertensive medications, but
      only 27.1% reached target blood pressure values of less than 130/80 mm Hg. Older
      patients took more antihypertensive medications, but there were no differences by
      sex. More than 90% were taking angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers, 66% were taking diuretics, 41% were taking beta
      blockers, and 38% were taking calcium channel blockers. We cannot describe the
      sequence in which antihypertensive medication classes were added, but analysis of
      patients taking multiple drug classes suggests that most patients were started on
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,
      followed by diuretics, beta-blockers, or calcium channel blockers. The most
      commonly used medications were prescribed at higher than two-thirds the maximum
      dose effective for hypertension. CONCLUSION: Hypertension is very common among
      family practice patients with type 2 diabetes; of those patients, few reach
      target blood pressures. Practice-based strategies to increase dosing and number
      of medications prescribed might be required.

PMID- 19602665
TI  - Detecting and addressing adolescent issues and concerns: evaluating the efficacy
      of a primary care previsit questionnaire.
AB  - OBJECTIVE: To assess the efficacy of a previsit questionnaire (PVQ), implemented
      without formal training, that was designed to screen for biomedical and
      psychosocial health issues and concerns among adolescent patients in a hospital
      based primary care clinic, and to examine the subsequent action taken for health
      issues and concerns identified with the PVQ. DESIGN: Retrospective review of
      adolescent medical charts, using a pre-post design. SETTING: An outpatient
      primary care clinic located in an urban teaching hospital in Montreal, Que.
      PARTICIPANTS: A total of 210 adolescent patients aged 13 to 19 who visited the
      clinic between 2000 and 2004. MAIN OUTCOME MEASURES: The type (medical vs
      psychosocial) and number of issues detected and actions taken by physicians in
      one-to-one consultations with adolescent patients 2 years before (2000-2002) and
      2 years after (2002-2004) PVQ implementation, as noted in the patients' medical
      charts. RESULTS: In total, 105 charts were reviewed for each group. An increase
      in the number of psychosocial issues was detected following the introduction of
      the PVQ. An increase in the frequency of action taken for psychosocial concerns
      and a decrease in the frequency of medical action taken by physicians were found
      after PVQ implementation. More notations related to psychosocial concerns were
      also found in the adolescents' charts after introduction of the PVQ. CONCLUSION:
      A PVQ is an effective strategy to improve adolescent screening for psychosocial
      issues and concerns. Implementing such a questionnaire requires no training and
      can therefore be easily incorporated into clinical practice.

PMID- 19602667
TI  - Outliers: extended families, better health outcomes: why everyone should have a
      family doctor.

PMID- 19602668
TI  - Stanniocalcin-1 suppresses superoxide generation in macrophages through induction
      of mitochondrial UCP2.
AB  - Mammalian STC1 decreases the mobility of macrophages and diminishes their
      response to chemokines. In the current experiments, we sought to determine the
      impact of STC1 on energy metabolism and superoxide generation in mouse
      macrophages. STC1 decreases ATP level in macrophages but does not affect the
      activity of respiratory chain complexes I-IV. STC1 induces the expression of
      mitochondrial UCP2, diminishing mitochondrial membrane potential and superoxide
      generation; studies in UCP2 null and gp91phox null macrophages suggest that
      suppression of superoxide by STC1 is UCP2-dependent yet is gp91phox-independent.
      Furthermore, STC1 blunts the effects of LPS on superoxide generation in
      macrophages. Exogenous STC1 is internalized by macrophages within 10 min and
      localizes to the mitochondria, suggesting a role for circulating and/or tissue
      derived STC1 in regulating macrophage function. STC1 induces arrest of the cell
      cycle at the G1 phase and reduces cell necrosis and apoptosis in serum-starved
      macrophages. Our data identify STC1 as a key regulator of superoxide generation
      in macrophages and suggest that STC1 may profoundly affect the
      immune/inflammatory response.

PMID- 19602669
TI  - Impaired osteoclastogenesis by staphylococcal lipoteichoic acid through Toll-like
      receptor 2 with partial involvement of MyD88.
AB  - Degenerative bone disease, marked by excessive loss of calcified matrix, is often
      associated with bacterial infections. Osteoclasts, which mediate the bone
      resorptive process, are derived mainly from myeloid precursor cells of the
      monocyte/macrophage lineage, from which cells with phagocytic and inflammatory
      capacities may alternatively arise. Here, we investigated the effect of LTA, a
      major cell-wall virulence factor of Gram-positive bacteria, on osteoclast
      differentiation. Osteoclast precursors were prepared from C57BL/6 mouse BM using
      M-CSF and RANKL. When osteoclastogenesis was induced in the presence of
      staphylococcal LTA, LTA dose-dependently inhibited the differentiation of
      osteoclast precursors to mature osteoclasts. A corresponding inhibition of bone
      resorptive function was observed in the reduced resorption area on calcium
      phosphate-coated culture plates. In contrast, the phagocytic and inflammatory
      potential of the osteoclast precursors increased in the presence of LTA. TLR2,
      known to recognize LTA, might be essential for the LTA inhibition of
      osteoclastogenesis, as the inhibition did not occur in the precursors from TLR2
      deficient mice. Importantly, MyD88-dependent and MyD88-independent pathways would
      participate in the inhibition, as determined using MyD88-deficient cells.
      Moreover, LTA inhibited phosphorylation of ERK and JNK in osteoclast precursors
      stimulated with M-CSF and RANKL, concomitantly with a decreased DNA-binding
      activity of AP-1. These results suggest that staphylococcal LTA inhibits
      osteoclast differentiation primarily through TLR2 but also in part through MyD88
      signaling, which in turn, inhibits activation of ERK, JNK, and AP-1.

PMID- 19602672
TI  - Lack of association of tegaserod with adverse cardiovascular outcomes in a
      matched case-control study.
AB  - Tegaserod is a first-in class selective serotonin 4 receptor agonist approved for
      the treatment of irritable bowel syndrome. In March 2007, the US Food and Drug
      Administration (FDA) suspended its use citing increased cardiovascular (CV)
      events in clinical trials. However, there is no known mechanistic basis for an
      adverse CV effect. To reassess the CV safety of tegaserod, teagaserod-treated
      patients (pts) in the Intermountain Healthcare database were identified (n =
      2603), matched 1:6 with untreated (n = 15,618) patients by age, sex, and date of
      tegaserod initiation, and followed for an average of 2.5 years. Age averaged 38.6
      +/- 13.5 years, and 94% were female. Cardiovascular event rates were low and
      similar in patients treated with tegaserod and matched untreated patients. For
      the primary composite CV endpoint, 54 (0.35%) untreated and 12 (0.46%) treated
      pts had an event (treated OR = 1.27, 95% CI: 0.68-2.38, P =.46), with 7 and 0
      events, respectively, occurring within 3 months. A total of 12 (0.1%) untreated
      and 1 (<0.1%) treated pts were hospitalized for a myocardial infarction (MI). 36
      (0.2%) untreated and 10 (0.4%) treated pts for a cardiovascular accident, and 1
      pt in each group for unstable angina. A total of 6 (<0.1%) untreated and no
      treated pts died from cardiac causes. Event rates were comparable to expected
      rates in this population of mostly premenopausal women. This large epidemiologic
      study failed to confirm a reported large event differential for tegaserod that
      was noted incidentally in a clinical trials database, suggesting that the prior
      observation may have been due to chance.

PMID- 19602673
TI  - The relationship between battered women's causal attributions for violence and
      coping efforts.
AB  - This study investigates the relationship between battered women's causal
      attributions for the violence they experience and their subsequent coping
      efforts. Causal attributions related to partner blame, excusing the violence, and
      the combination of partner blame and excusing the violence were regressed on six
      categories of coping strategies: placating, resistance, formal help source,
      informal help source, safety planning, and legal strategies. Of the 793 women
      approached outside of a battered women's shelter and the district court, 406
      women completed the baseline measure. It was found that women who hold their
      partners accountable for abuse are more likely than women who excuse the violence
      to utilize more overall coping strategies. Also, women who blame their partners
      for the abuse utilize both more active and more public coping efforts. After
      accounting for the effects of ethnicity, violence severity, and excusing the
      violence, the percentage of blame attributions endorsed predicted informal (R( 2)
      = .077, p = .001) and safety planning (R(2) = .054, p = .014) strategies. After
      controlling for ethnicity, violence severity, and blaming, the percentage of
      excuse attributions predicted placating (R(2) = .103, p = .016) strategies.

PMID- 19602674
TI  - Relationship between recent life events, social supports, and attitudes to
      domestic violence: predictive roles in behaviors.
AB  - The purpose of the study was to assess the relationship between recent life
      events, attitudes to domestic violence (DV), and DV behaviors among perpetrators
      of DV in China. A total of 600 participants were assessed for recent life events,
      psychological functioning, social support, and attitudes to DV. Results
      demonstrated that recent negative life events (NLE) and attitudes to DV were
      predictive factors for DV among perpetrators of DV, after controlling for
      demographic variables, psychological functioning, and social supports. The
      findings suggest that recent life events are potential factors contributing to
      behaviors of DV. The importance of changes of negative attitudes to DV among
      perpetrators was highly emphasized. Intervention and prevention programs based on
      psychological functioning and social support in relation to perpetrators of DV
      may be useful to control DV in China.

PMID- 19602675
TI  - The cover. Muir glacier.

PMID- 19602670
TI  - Alcohol abuse and pulmonary disease.
AB  - ARDS is a severe form of lung injury characterized by increased permeability of
      the alveolar capillary membrane, diffuse alveolar damage, the accumulation of
      proteinaceous interstitial and intra-alveolar edema, and the presence of hyaline
      membranes. These pathological changes are accompanied by physiological
      alterations, including severe hypoxemia, an increase in pulmonary dead space, and
      decreased pulmonary compliance. Approximately 200,000 individuals develop ARDS in
      the United States each year, and nearly 50% of these patients have a history of
      alcohol abuse. We have identified alcohol abuse as an independent risk factor for
      the development of ARDS, and more recent studies have validated these findings in
      patients following lung resection and blood transfusion. In ARDS survivors,
      alcohol abuse is also associated with an increased duration of mechanical
      ventilation and prolonged ICU length of stay. Despite studies aimed at improving
      outcomes in patients with ARDS, the mortality remains high at > 40%]. For those
      who abuse alcohol, the mortality is even higher, at 65%. In this review, we will
      discuss the relationship between alcohol abuse and ARDS, the effects of alcohol
      abuse on pulmonary function, and future directions and potential therapeutic
      targets for patients at risk for ARDS as a result of alcohol abuse, which impairs
      immune function, decreases pulmonary antioxidant capacity, decreases alveolar
      epithelial cell function, alters activation of the renin angiotensin system, and
      impairs GM-CSF signaling. These pathways represent potential therapeutic targets
      for patients at risk for ARDS as a result of alcohol abuse.

PMID- 19602676
TI  - A piece of my mind. Rediscovering my voice.

PMID- 19602677
TI  - Guideline for pregnancy weight gain offers targets for obese women.

PMID- 19602678
TI  - Unvaccinated children face pertussis risk: some parents fear vaccine more than
      infection.

PMID- 19602679
TI  - Group offers advice on safe extraction of lead wires in implantable heart
      devices.

PMID- 19602680
TI  - Carotid atherosclerosis progression and ACAT inhibition.

PMID- 19602681
TI  - Carotid atherosclerosis progression and ACAT inhibition.

PMID- 19602682
TI  - Religious coping and life-prolonging care.

PMID- 19602683
TI  - Religious coping and life-prolonging care.

PMID- 19602684
TI  - Diagnostic errors and patient safety.

PMID- 19602685
TI  - Diagnostic errors and patient safety.

PMID- 19602686
TI  - A network model of a cooperative genetic landscape in brain tumors.
AB  - CONTEXT: Gliomas, particularly glioblastomas, are among the deadliest of human
      tumors. Gliomas emerge through the accumulation of recurrent chromosomal
      alterations, some of which target yet-to-be-discovered cancer genes. A persistent
      question concerns the biological basis for the coselection of these alterations
      during gliomagenesis. OBJECTIVES: To describe a network model of a cooperative
      genetic landscape in gliomas and to evaluate its clinical relevance. DESIGN,
      SETTING, AND PATIENTS: Multidimensional genomic profiles and clinical profiles of
      501 patients with gliomas (45 tumors in an initial discovery set collected
      between 2001 and 2004 and 456 tumors in validation sets made public between 2006
      and 2008) from multiple academic centers in the United States and The Cancer
      Genome Atlas Pilot Project (TCGA). MAIN OUTCOME MEASURES: Identification of genes
      with coincident genetic alterations, correlated gene dosage and gene expression,
      and multiple functional interactions; association between those genes and patient
      survival. RESULTS: Gliomas select for a nonrandom genetic landscape-a consistent
      pattern of chromosomal alterations-that involves altered regions ("territories")
      on chromosomes 1p, 7, 8q, 9p, 10, 12q, 13q, 19q, 20, and 22q (false-discovery
      rate-corrected P<.05). A network model shows that these territories harbor genes
      with putative synergistic, tumor-promoting relationships. The coalteration of the
      most interactive of these genes in glioblastoma is associated with unfavorable
      patient survival. A multigene risk scoring model based on 7 landscape genes
      (POLD2, CYCS, MYC, AKR1C3, YME1L1, ANXA7, and PDCD4) is associated with the
      duration of overall survival in 189 glioblastoma samples from TCGA (global log
      rank P = .02 comparing 3 survival curves for patients with 0-2, 3-4, and 5-7
      dosage-altered genes). Groups of patients with 0 to 2 (low-risk group) and 5 to 7
      (high-risk group) dosage-altered genes experienced 49.24 and 79.56 deaths per 100
      person-years (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.10-2.40;
      Cox regression model P = .02), respectively. These associations with survival are
      validated using gene expression data in 3 independent glioma studies, comprising
      76 (global log-rank P = .003; 47.89 vs 15.13 deaths per 100 person-years for high
      risk vs low risk; Cox model HR, 3.04; 95% CI, 1.49-6.20; P = .002) and 70 (global
      log-rank P = .008; 83.43 vs 16.14 deaths per 100 person-years for high risk vs
      low risk; HR, 3.86; 95% CI, 1.59-9.35; P = .003) high-grade gliomas and 191
      glioblastomas (global log-rank P = .002; 83.23 vs 34.16 deaths per 100 person
      years for high risk vs low risk; HR, 2.27; 95% CI, 1.44-3.58; P<.001).
      CONCLUSIONS: The alteration of multiple networking genes by recurrent chromosomal
      aberrations in gliomas deregulates critical signaling pathways through multiple,
      cooperative mechanisms. These mutations, which are likely due to nonrandom
      selection of a distinct genetic landscape during gliomagenesis, are associated
      with patient prognosis.

PMID- 19602688
TI  - Prevalence and repair of intraoperatively diagnosed patent foramen ovale and
      association with perioperative outcomes and long-term survival.
AB  - CONTEXT: A recent survey suggested that cardiothoracic surgeons may alter planned
      procedures to repair incidentally discovered patent foramen ovale (PFO). How
      frequently this occurs and the impact on outcomes remain unknown. OBJECTIVE: To
      measure the frequency of incidentally discovered PFO closure during
      cardiothoracic surgery and determine its perioperative and long-term impact.
      DESIGN, SETTING, AND PATIENTS: We reviewed the intraoperative transesophageal
      echocardiograms of 13,092 patients without prior diagnosis of PFO or atrial
      septal defect undergoing surgery at the Cleveland Clinic, Cleveland, Ohio, from
      1995 through 2006. Postoperative outcomes were prospectively collected until
      discharge. MAIN OUTCOME MEASURES: All-cause hospital mortality and stroke were
      predetermined primary outcomes; length of hospital stay, length of intensive care
      unit stay, and time on cardiopulmonary bypass were secondary outcomes. RESULTS:
      Intraoperative PFO was diagnosed in 2277 patients in the study population (17%),
      and risk factors for stroke were similar in patients with and without PFO. After
      propensity matching was performed with the comparator groups, patients with PFO
      demonstrated similar rates of in-hospital death (3.4% vs 2.6%, P = .11) and
      postoperative stroke (2.3% vs 2.3%, P = .84). Surgical closure was performed in
      639 PFO patients (28%), and surgeons were more likely to close defects in
      patients who were younger (mean [SD] age, 61.1 [14] vs 64.4 [13] years; P <
      .001), were undergoing mitral or tricuspid valve surgery (51% vs 32%, P < .001),
      or had history of transient ischemic attack or stroke (16% vs 10%, P < .001).
      Patients with repaired PFO demonstrated a 2.47-times greater odds (95% confidence
      interval, 1.02-6.00) of having a postoperative stroke compared with those with
      unrepaired PFO (2.8% vs 1.2%, P = .04). Long-term analysis demonstrated that PFO
      repair was associated with no survival difference (P = .12). CONCLUSIONS:
      Incidental PFO is common in patients undergoing cardiothoracic surgery but is not
      associated with increased perioperative morbidity or mortality. Surgical closure
      appears unrelated to long-term survival and may increase postoperative stroke
      risk.

PMID- 19602687
TI  - Monosomy of chromosome 10 associated with dysregulation of epidermal growth
      factor signaling in glioblastomas.
AB  - CONTEXT: Glioblastomas--uniformly fatal brain tumors--often have both monosomy of
      chromosome 10 and gains of the epidermal growth factor receptor (EGFR) gene locus
      on chromosome 7, an association for which the mechanism is poorly understood.
      OBJECTIVES: To assess whether coselection of EGFR gains on 7p12 and monosomy 10
      in glioblastomas promotes tumorigenic epidermal growth factor (EGF) signaling
      through loss of the annexin A7 (ANXA7) gene on 10q21.1-q21.2 and whether ANXA7
      acts as a tumor suppressor gene by regulating EGFR in glioblastomas. DESIGN,
      SETTING, AND PATIENTS: Multidimensional analysis of gene, coding sequence,
      promoter methylation, messenger RNA (mRNA) transcript, protein data for ANXA7
      (and EGFR), and clinical patient data profiles of 543 high-grade gliomas from US
      medical centers and The Cancer Genome Atlas pilot project (made public 2006-2008;
      and unpublished, tumors collected 2001-2008). Functional analyses using LN229 and
      U87 glioblastoma cells. MAIN OUTCOME MEASURES: Associations among ANXA7 gene
      dosage, coding sequence, promoter methylation, mRNA transcript, and protein
      expression. Effect of ANXA7 haploinsufficiency on EGFR signaling and patient
      survival. Joint effects of loss of ANXA7 and gain of EGFR expression on
      tumorigenesis. RESULTS: Heterozygous ANXA7 gene deletion is associated with
      significant loss of ANXA7 mRNA transcript expression (P = 1 x 10(-15); linear
      regression) and a reduction (mean [SEM]) of 91.5% (2.3%) of ANXA7 protein
      expression compared with ANXA7 wild-type glioblastomas (P = .004; unpaired t
      test). ANXA7 loss of function stabilizes the EGFR protein (72%-744% increase in
      EGFR protein abundance) and augments EGFR transforming signaling in glioblastoma
      cells. ANXA7 haploinsufficiency doubles tumorigenic potential of glioblastoma
      cells, and combined ANXA7 knockdown and EGFR overexpression promotes
      tumorigenicity synergistically. The heterozygous loss of ANXA7 in approximately
      75% of glioblastomas in the The Cancer Genome Atlas plus infrequency of ANXA7
      mutation (approximately 6% of tumors) indicates its role as a haploinsufficiency
      gene. ANXA7 mRNA transcript expression, dichotomized at the median, associates
      with patient survival in 191 glioblastomas (log-rank P = .008; hazard ratio [HR],
      0.667; 95% confidence interval [CI], 0.493-0.902; 46.9 vs 74.8 deaths/100 person
      years for high vs low ANXA7 mRNA expression) and with a separate group of 180
      high-grade gliomas (log-rank P = .00003; HR, 0.476; 95% CI, 0.333-0.680; 21.8 vs
      50.0 deaths/100 person-years for high vs low ANXA7 mRNA expression). Deletion of
      the ANXA7 gene associates with poor patient survival in 189 glioblastomas (log
      rank P = .042; HR, 0.686; 95% CI, 0.476-0.989; 54.0 vs 80.1 deaths/100 person
      years for wild-type ANXA7 vs ANXA7 deletion). CONCLUSION: Haploinsufficiency of
      the tumor suppressor ANXA7 due to monosomy of chromosome 10 provides a clinically
      relevant mechanism to augment EGFR signaling in glioblastomas beyond that
      resulting from amplification of the EGFR gene.

PMID- 19602689
TI  - Hormone therapy and ovarian cancer.
AB  - CONTEXT: Studies have suggested an increased risk of ovarian cancer among women
      taking postmenopausal hormone therapy. Data are sparse on the differential
      effects of formulations, regimens, and routes of administration. OBJECTIVE: To
      assess risk of ovarian cancer in perimenopausal and postmenopausal women
      receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective
      cohort study including all Danish women aged 50 through 79 years from 1995
      through 2005 through individual linkage to Danish national registers. Redeemed
      prescription data from the National Register of Medicinal Product Statistics
      provided individually updated exposure information. The National Cancer Register
      and Pathology Register provided ovarian cancer incidence data. Information on
      confounding factors and effect modifiers was from other national registers.
      Poisson regression analyses with 5-year age bands included hormone exposures as
      time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone
      sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer.
      RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068
      incident ovarian cancers, of which 2681 were epithelial cancers, were detected.
      Compared with women who never took hormone therapy, current users of hormones had
      incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval
      [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The
      risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46);
      more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72
      (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current
      users the risk of ovarian cancer did not differ significantly with different
      hormone therapies or duration of use. The incidence rates in current and never
      users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an
      absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This
      approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy
      each year. CONCLUSION: Regardless of the duration of use, the formulation,
      estrogen dose, regimen, progestin type, and route of administration, hormone
      therapy was associated with an increased risk of ovarian cancer.

PMID- 19602691
TI  - Health impact assessment: a step toward health in all policies.

PMID- 19602690
TI  - Bronchiolitis obliterans after allogeneic hematopoietic stem cell
      transplantation.
AB  - With improvements in supportive care, both long-term survival following
      allogeneic hematopoietic stem cell transplantations (HSCTs) and the indications
      for this procedure have increased. As a result, the number of patients living
      with long-term toxic effects due to HSCT has increased. A once rare condition of
      the donor immune cells attacking healthy host tissues, termed chronic graft-vs
      host disease, has become a more common phenomenon. When chronic graft-vs-host
      disease affects the lung tissue, bronchiolitis obliterans syndrome ensues. Recent
      data suggest that bronchiolitis obliterans syndrome may affect up to 6% of HSCT
      recipients and dramatically alters survival, with overall survival of only 13% at
      5 years. These statistics have not improved since the first presentation of this
      disease over 20 years ago. Challenges to the progress of medical management of
      bronchiolitis obliterans syndrome include difficulties and delays in diagnosis
      and a paucity of data on pathogenesis to direct new therapies. This article
      critically evaluates the current diagnostic criteria for bronchiolitis obliterans
      syndrome and reviews the epidemiology, pathogenesis, and available treatments.
      Improvements in survival will likely require early disease recognition, allowing
      for therapeutic modulation of disease prior to the development of irreversible
      airway obliteration.

PMID- 19602692
TI  - Integrating clinical care and community health: delivering health.

PMID- 19602693
TI  - "Research" in community-partnered, participatory research.

PMID- 19602694
TI  - Development of hepatitis B vaccine.

PMID- 19602695
TI  - One step forward toward identification of the genetic signature of glioblastomas.

PMID- 19602696
TI  - JAMA patient page. Hematopoietic stem cell transplantation.

PMID- 19602701
TI  - Underlying genetic models of inheritance in established type 2 diabetes
      associations.
AB  - For most associations of common single nucleotide polymorphisms (SNPs) with
      common diseases, the genetic model of inheritance is unknown. The authors
      extended and applied a Bayesian meta-analysis approach to data from 19 studies on
      17 replicated associations with type 2 diabetes. For 13 SNPs, the data fitted
      very well to an additive model of inheritance for the diabetes risk allele; for 4
      SNPs, the data were consistent with either an additive model or a dominant model;
      and for 2 SNPs, the data were consistent with an additive or recessive model.
      Results were robust to the use of different priors and after exclusion of data
      for which index SNPs had been examined indirectly through proxy markers. The
      Bayesian meta-analysis model yielded point estimates for the genetic effects that
      were very similar to those previously reported based on fixed- or random-effects
      models, but uncertainty about several of the effects was substantially larger.
      The authors also examined the extent of between-study heterogeneity in the
      genetic model and found generally small between-study deviation values for the
      genetic model parameter. Heterosis could not be excluded for 4 SNPs. Information
      on the genetic model of robustly replicated association signals derived from
      genome-wide association studies may be useful for predictive modeling and for
      designing biologic and functional experiments.

PMID- 19602703
TI  - Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase
      Nedd4-2.
AB  - E3 ubiquitin ligases catalyze ubiquitination, which can target specific proteins
      for degradation. Although a growing number of E3 ubiquitin ligases and their
      targets have been identified, much less is known about the mechanisms that
      regulate their activity. A convergence of data indicate that phosphorylation
      regulates the binding of Nedd4-2, a HECT (homologous to the E6-AP C terminus)
      domain E3 ubiquitin ligase, to its target, the epithelial Na(+) channel ENaC.
      Nedd4-2 phosphorylation is emerging as a central convergence point for the
      regulation of epithelial Na(+) transport.

PMID- 19602702
TI  - Passive smoking and pancreatic cancer in women: a prospective cohort study.
AB  - BACKGROUND: Active smoking is an established risk factor for pancreatic cancer,
      but the role of passive smoking in pancreatic carcinogenesis remains unclear. We
      aimed to examine whether environmental tobacco smoke is associated with
      pancreatic cancer risk. METHODS: We prospectively examined 86,673 women in the
      Nurses' Health Study. History of exposure to environmental tobacco smoke was
      assessed through questionnaires in 1982. Relative risks (RR) and 95% confidence
      intervals (CI) were estimated using Cox proportional hazards models. RESULTS:
      During 24 years of follow-up (1982-2006), 384 women were diagnosed with
      pancreatic cancer. Maternal smoking significantly increased the risk of
      pancreatic cancer (RR, 1.42; 95% CI, 1.07-1.89), whereas paternal smoking was not
      related to the risk (RR, 0.97; 95% CI, 0.77-1.21). The risk associated with
      maternal smoking remained elevated, albeit not significant, among never smokers
      (RR, 1.52; 95% CI, 0.97-2.39). No association was found for adult passive
      exposure at work or at home. CONCLUSIONS: The positive association with maternal
      smoking suggests that environmental tobacco smoke, potentially in utero or in
      early life, may be associated with pancreatic cancer.

PMID- 19602704
TI  - Control of neuronal growth cone navigation by asymmetric inositol 1,4,5
      trisphosphate signals.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) is generally viewed as a global messenger
      that increases cytosolic calcium ion (Ca(2+)) concentration. However, the
      spatiotemporal dynamics of IP(3) and the functional significance of localized
      IP(3) production in cell polarity remain largely unknown. Here, we demonstrate
      the critical role of spatially restricted IP(3) signals in axon guidance. We
      found that IP(3) and ensuing Ca(2+) signals were produced asymmetrically across
      growth cones exposed to an extracellular gradient of nerve growth factor (NGF)
      and mediated growth cone turning responses to NGF. Moreover, photolysis-induced
      production of IP(3) on one side of a growth cone was sufficient to initiate
      growth cone turning toward the side with the higher concentration of IP(3). Thus,
      locally produced IP(3) encodes spatial information that polarizes the growth cone
      for guided migration.

PMID- 19602705
TI  - Conflict between nursing home staff and residents' families: does it increase
      burnout?
AB  - OBJECTIVE: In this study, the authors examine the influence of conflict between
      nursing home staff and family members of residents on staff burnout. METHOD: Data
      were collected from interviews with a representative sample of 655 nursing home
      nurses and nursing assistants. Hypotheses were tested using structural equation
      modeling. RESULTS: Results indicate that conflict with family members increases
      staff burnout and decreases staff satisfaction. Staff and family conflict
      increases when staff members feel they do not have enough time to complete
      required tasks. Level of conflict decreases when staff perceive that family
      members have care expectations that are similar to their own. Interestingly,
      staff who have personal experience as family caregivers are more likely to report
      conflict with family members of residents, a result that necessitates further
      study. DISCUSSION: Staff burnout and dissatisfaction affects both individuals and
      organizations. Policy that addresses staff and family interaction can have an
      important place in the design and delivery of long-term care.

PMID- 19602706
TI  - A longitudinal investigation of inattention and preliteracy development.
AB  - OBJECTIVE: The link between significant attention problems and reading
      difficulties among school-age children is clear, but few have examined the impact
      of early inattention on preliteracy development. This longitudinal study examines
      this link. METHOD: A total of 47 children had repeated measures of teacher-rated
      attention problems and three key preliteracy skills (phonemic awareness, letter
      knowledge, and rapid naming) in both preschool and kindergarten. RESULTS: Teacher
      reported attention problems in preschool significantly and negatively predicted
      both phonemic awareness and letter naming scores 1 year later, even after
      controlling for initial language ability and preschool performance on these
      tasks. Levels of preschool inattention did not significantly predict rapid
      automatic naming 1 year later. Likewise, preschool preliteracy scores did not
      predict attention problems in kindergarten. CONCLUSION: Early attention problems
      may interfere with the acquisition of certain preliteracy skills. Implications of
      these findings and directions for future research are presented.

PMID- 19602707
TI  - In planta proteomics and proteogenomics of the biotrophic barley fungal pathogen
      Blumeria graminis f. sp. hordei.
AB  - To further our understanding of powdery mildew biology during infection, we
      undertook a systematic shotgun proteomics analysis of the obligate biotroph
      Blumeria graminis f. sp. hordei at different stages of development in the host.
      Moreover we used a proteogenomics approach to feed information into the
      annotation of the newly sequenced genome. We analyzed and compared the proteomes
      from three stages of development representing different functions during the
      plant-dependent vegetative life cycle of this fungus. We identified 441 proteins
      in ungerminated spores, 775 proteins in epiphytic sporulating hyphae, and 47
      proteins from haustoria inside barley leaf epidermal cells and used the data to
      aid annotation of the B. graminis f. sp. hordei genome. We also compared the
      differences in the protein complement of these key stages. Although confirming
      some of the previously reported findings and models derived from the analysis of
      transcriptome dynamics, our results also suggest that the intracellular haustoria
      are subject to stress possibly as a result of the plant defense strategy,
      including the production of reactive oxygen species. In addition, a number of
      small haustorial proteins with a predicted N-terminal signal peptide for
      secretion were identified in infected tissues: these represent candidate effector
      proteins that may play a role in controlling host metabolism and immunity.

PMID- 19602709
TI  - Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize
      different CD34+ cell populations based on global gene and microRNA expression
      signatures.
AB  - Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize
      peripheral blood stem cells by different mechanisms. A rhesus macaque model was
      used to compare plerixafor and G-CSF-mobilized CD34(+) cells. Three peripheral
      blood stem cell concentrates were collected from 3 macaques treated with G-CSF,
      plerixafor, or plerixafor plus G-CSF. CD34(+) cells were isolated by
      immunoselection and were analyzed by global gene and microRNA (miR) expression
      microarrays. Unsupervised hierarchical clustering of the gene expression data
      separated the CD34(+) cells into 3 groups based on mobilization regimen.
      Plerixafor-mobilized cells were enriched for B cells, T cells, and mast cell
      genes, and G-CSF-mobilized cells were enriched for neutrophils and mononuclear
      phagocyte genes. Genes up-regulated in plerixafor plus G-CSF-mobilized CD34(+)
      cells included many that were not up-regulated by either agent alone. Two
      hematopoietic progenitor cell miR, miR-10 and miR-126, and a dendritic cell miR,
      miR-155, were up-regulated in G-CSF-mobilized CD34(+) cells. A pre-B-cell acute
      lymphocytic leukemia miR, miR-143-3p, and a T-cell miR, miR-143-5p, were up
      regulated in plerixafor plus G-CSF-mobilized cells. The composition of CD34(+)
      cells is dependent on the mobilization protocol. Plerixafor-mobilized CD34(+)
      cells include more B-, T-, and mast cell precursors, whereas G-CSF-mobilized
      cells have more neutrophil and mononuclear phagocyte precursors.

PMID- 19602708
TI  - Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17
      cells in graft-versus-host disease.
AB  - In acute graft-versus-host disease (GVHD), naive donor CD4(+) T cells recognize
      alloantigens on host antigen-presenting cells and differentiate into T helper
      (Th) subsets (Th1, Th2, and Th17 cells), but the role of Th subsets in GVHD
      pathogenesis is incompletely characterized. Here we report that, in an MHC
      mismatched model of C57BL/6 donor to BALB/c recipient, WT donor CD4(+) T cells
      predominantly differentiated into Th1 cells and preferentially mediated GVHD
      tissue damage in gut and liver. However, absence of interferon-gamma (IFN-gamma)
      in CD4(+) T cells resulted in augmented Th2 and Th17 differentiation and
      exacerbated tissue damage in lung and skin; absence of both IL-4 and IFN-gamma
      resulted in augmented Th17 differentiation and preferential, although not
      exclusive, tissue damage in skin; and absence of both IFN-gamma and IL-17 led to
      further augmentation of Th2 differentiation and idiopathic pneumonia. The tissue
      specific GVHD mediated by Th1, Th2, and Th17 cells was in part associated with
      their tissue-specific migration mediated by differential expression of chemokine
      receptors. Furthermore, lack of tissue expression of the IFN-gamma-inducible B7
      H1 played a critical role in augmenting the Th2-mediated idiopathic pneumonia.
      These results indicate donor CD4(+) T cells can reciprocally differentiate into
      Th1, Th2, and Th17 cells that mediate organ-specific GVHD.

PMID- 19602710
TI  - Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is
      associated with resistance to chemotherapy and inferior outcome.
AB  - To evaluate internal tandem duplication (ITD) insertion sites and length as well
      as their clinical impact in younger adult patients with FLT3-ITD-positive acute
      myeloid leukemia (AML), sequencing after DNA-based amplification was performed in
      diagnostic samples from 241 FLT3-ITD-mutated patients. All patients were treated
      on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients
      had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48
      nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized
      according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD),
      n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1
      (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated
      with functional regions (P < .001). In multivariable analyses, ITD integration
      site in the beta1-sheet was identified as an unfavorable prognostic factor for
      achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free
      survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio,
      1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important
      unfavorable prognostic factor in young adult patients with FLT3-ITD-positive AML.
      The clinical trials described herein have been registered as follows: AML HD93
      (already published in 2003), AML HD98A (NCT00146120;
      http://www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242;
      http://www.ClinicalTrials.gov).

PMID- 19602712
TI  - Why has mortality from coronary heart disease in young adults levelled off?

PMID- 19602711
TI  - Human T-cell leukemia virus type 2 produces a spliced antisense transcript
      encoding a protein that lacks a classic bZIP domain but still inhibits Tax2
      mediated transcription.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses
      infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a
      protein that could play a role in the development of leukemia in infected
      patients. Herein, we demonstrate that the complementary strand of the HTLV-2
      genome also encodes a protein that we named APH-2 for "antisense protein of HTLV
      2." APH-2 mRNA is spliced, polyadenylated, and initiates in the 3'-long terminal
      repeat at different positions. This transcript was detected in all HTLV-2
      infected cell lines and short-term culture of lymphocytes obtained from HTLV-2
      African patients tested and in 4 of 15 HTLV-2-infected blood donors. The APH-2
      protein is 183 amino acids long, is localized in the cell nucleus, and is
      detected in vivo. Despite the lack of a consensus basic leucine zipper domain,
      APH-2 interacts with cyclic adenosine monophosphate-response element binding
      protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells
      and in cells transfected with an HTLV-2 molecular clone. Altogether, our results
      demonstrate the existence of an antisense strand-encoded protein in HTLV-2, which
      could represent an important player in the development of disorders, such as
      lymphocytosis, which is frequently observed in HTLV-2 patients.

PMID- 19602713
TI  - Coronary heart disease mortality among young adults in Scotland in relation to
      social inequalities: time trend study.
AB  - OBJECTIVE: To examine recent trends and social inequalities in age specific
      coronary heart disease mortality. DESIGN: Time trend analysis using joinpoint
      regression. SETTING: Scotland, 1986-2006. PARTICIPANTS: Men and women aged 35
      years and over. MAIN OUTCOME MEASURES: Age adjusted and age, sex, and deprivation
      specific coronary heart disease mortality. RESULTS: Persistent sixfold social
      differentials in coronary heart disease mortality were seen between the most
      deprived and the most affluent groups aged 35-44 years. These differentials
      diminished with increasing age but equalised only above 85 years. Between 1986
      and 2006, overall, age adjusted coronary heart disease mortality decreased by 61%
      in men and by 56% in women. Among middle aged and older adults, mortality
      continued to decrease fairly steadily throughout the period. However, coronary
      heart disease mortality levelled from 1994 onwards among young men and women aged
      35-44 years. Rates in men and women aged 45-54 showed similar flattening from
      about 2003. Rates in women aged 55-64 may also now be flattening. The flattening
      of coronary heart disease mortality in younger men and women was confined to the
      two most deprived fifths. CONCLUSIONS: Premature death from coronary heart
      disease remains a major contributor to social inequalities. Furthermore, the
      flattening of the decline in mortality for coronary heart disease among younger
      adults may represent an early warning sign. The observed trends were confined to
      the most deprived groups. Marked deterioration in medical management of coronary
      heart disease seems implausible. Unfavourable trends in the major risk factors
      for coronary heart disease (smoking and poor diet) thus provide the most likely
      explanation for these inequalities.

PMID- 19602714
TI  - Assessing the severity of the novel influenza A/H1N1 pandemic.

PMID- 19602716
TI  - Social inequalities in mortality: a problem of cognitive function?

PMID- 19602717
TI  - Direct-to-consumer/patient advertising of genetic testing: a position statement
      of the American College of Clinical Pharmacology.

PMID- 19602715
TI  - Does IQ explain socio-economic differentials in total and cardiovascular disease
      mortality? Comparison with the explanatory power of traditional cardiovascular
      disease risk factors in the Vietnam Experience Study.
AB  - AIMS: The aim of this study was to examine the explanatory power of intelligence
      (IQ) compared with traditional cardiovascular disease (CVD) risk factors in the
      relationship of socio-economic disadvantage with total and CVD mortality, that is
      the extent to which IQ may account for the variance in this well-documented
      association. METHODS AND RESULTS: Cohort study of 4289 US male former military
      personnel with data on four widely used markers of socio-economic position (early
      adulthood and current income, occupational prestige, and education), IQ test
      scores (early adulthood and middle-age), a range of nine established CVD risk
      factors (systolic and diastolic blood pressure, total blood cholesterol, HDL
      cholesterol, body mass index, smoking, blood glucose, resting heart rate, and
      forced expiratory volume in 1 s), and later mortality. We used the relative index
      of inequality (RII) to quantify the relation between each index of socio-economic
      position and mortality. Fifteen years of mortality surveillance gave rise to 237
      deaths (62 from CVD and 175 from 'other' causes). In age-adjusted analyses, as
      expected, each of the four indices of socio-economic position was inversely
      associated with total, CVD, and 'other' causes of mortality, such that elevated
      rates were evident in the most socio-economically disadvantaged men. When IQ in
      middle-age was introduced to the age-adjusted model, there was marked attenuation
      in the RII across the socio-economic predictors for total mortality (average 50%
      attenuation in RII), CVD (55%), and 'other' causes of death (49%). When the nine
      traditional risk factors were added to the age-adjusted model, the comparable
      reduction in RII was less marked than that seen after IQ adjustment: all-causes
      (40%), CVD (40%), and 'other' mortality (43%). Adding IQ to the latter model
      resulted in marked, additional explanatory power for all outcomes in comparison
      to the age-adjusted analyses: all-causes (63%), CVD (63%), and 'other' mortality
      (65%). When we utilized IQ in early adulthood rather than middle-age as an
      explanatory variable, the attenuating effect on the socio-economic gradient was
      less pronounced although the same pattern was still present. CONCLUSION: In the
      present analyses of socio-economic gradients in total and CVD mortality, IQ
      appeared to offer greater explanatory power than that apparent for traditional
      CVD risk factors.

PMID- 19602718
TI  - Pharmacokinetic and pharmacodynamic modeling of a copper-selective chelator
      (TETA) in healthy adults.
AB  - The population pharmacokinetics (PK) and pharmacodynamics (PD) of
      triethylenetetramine (TETA) dihydrochloride (trientine, GC811007) administered
      orally as 100-, 300-, 600-, or 1800-mg twice-daily doses were assessed in healthy
      adult male and female volunteers. This study was a randomized, double-blind,
      placebo-controlled, group-sequential, dose-escalating design. Forty participants,
      10 per dose level (8 receiving TETA, 2 receiving placebo), received twice-daily
      doses for 14 consecutive days. A 2-compartment model for the PK and a linear
      direct effect model for drug-induced copper excretion (PD) were employed. The
      population PK/PD model was applied using the NONMEM software. Covariates tested
      were glomerular filtration rate (GFR), body weight, and gender. Multiple daily
      doses of TETA were safe and generally well tolerated. The linear 2-compartment
      model with first-order absorption well characterized the serum concentration
      data. Although its role was small, GFR had a statistically significant (P < .05)
      influence on systemic clearance (CL/F). The augmentation of copper excretion was
      well described by a direct linear model in which the slope was related to GFR and
      gender (P < .001). The intersubject coefficient of variation was 22.2% for slope
      (SL) and 82.5% for intercept (ER0). TETA has consistent single/multiple-dose
      pharmacokinetics and dose-proportional and serum concentration-proportional
      effects on enhancing copper excretion.

PMID- 19602719
TI  - A thorough QTc study to assess the effect of sitagliptin, a DPP4 inhibitor, on
      ventricular repolarization in healthy subjects.
AB  - A randomized, double-blind, placebo-controlled, 4-period crossover study was
      performed with a single oral dose of sitagliptin (100 mg, 800 mg), moxifloxacin
      (400 mg), and placebo in order to provide a rigorous assessment of the effect of
      sitagliptin on ventricular repolarization based on the ICH E14 guidance. The
      clinical dose of sitagliptin 100 mg was not associated with an increase in QTc
      interval, corrected using the Fridericia correction (QTcf), at any time point.
      The supratherapeutic 800-mg dose of sitagliptin was generally well tolerated and
      was associated with minimal, clinically insignificant prolongation of the QTcf
      interval at concentrations approximately 11-fold higher than maximal
      concentrations following the 100-mg clinical dose. The PK/QTc model demonstrated
      a shallow relationship between the plasma concentration of sitagliptin and the
      placebo-subtracted QTcf change from baseline, with a 0.59-millisecond increase in
      QTc for every 1000-nM increment in sitagliptin plasma concentration. The
      sensitivity of the assay to detect modest increases in QTc interval was
      established with the active control moxifloxacin. In conclusion, at clinically
      relevant concentrations, sitagliptin is not associated with clinically meaningful
      QTcf prolongation.

PMID- 19602721
TI  - Prediction of prasugrel active metabolite concentrations from 2 downstream
      inactive metabolite concentrations using multilinear regression analysis.
AB  - Prasugrel is a thienopyridine prodrug that is metabolized to an active metabolite
      (Pras-AM), which inhibits adenosine diphosphate (ADP)-induced platelet
      aggregation. The study objective was to describe a multilinear regression
      correlation model that was used to quantitatively predict concentrations of Pras
      AM from downstream inactive metabolites, R-119251 and R-106583, for the purpose
      of estimating Pras-AM exposure in patients in the TRITON-TIMI 38 substudies. The
      model development included 1462 Pras-AM, 1345 R-119251, and 1456 R-106583
      concentration data points from 103 healthy participants with a prasugrel dose
      range of 15 to 80 mg. The model was shown to provide good correlation between
      predicted and observed concentrations with only a minor deviation of
      approximately 6% from the unity line and described the variability within
      approximately 4.5%. Examination of the data indicated that regardless of
      ethnicity, age, weight, moderate hepatic impairment, or renal impairment,
      predictions were reliable. Predicted Pras-AM concentrations in TRITON-TIMI 38
      were comparable with historical data.

PMID- 19602722
TI  - Expression and organization of basement membranes and focal adhesion proteins in
      pregnant myometrium is regulated by uterine stretch.
AB  - The mechanisms underlying the preparation of the uterus for labor are not fully
      understood. We have previously found a significant increase in the expression of
      messenger RNA (mRNAs) encoding extracellular basement membrane (BM) proteins of
      the smooth muscle cells (SMCs) in late pregnant rat myometrium. At term, the
      myometrium is stretched by growing fetuses and these mechanical signals are
      transmitted from extracellular matrix into SMCs through focal adhesions (FA). The
      aim of this study was to investigate the effect of gravidity on the expression
      and spatiotemporal distribution of major BM proteins, laminin-gamma2 and collagen
      IV, as well as typical FA constituents, vinculin and paxillin, in the myometrium
      during gestation and parturition, using a unilaterally pregnant rat model. We
      found that the expression of laminin-gamma2 and collagen IV proteins increased
      significantly with gestational age (P < .05) and was dependent on gravidity
      whereas vinculin and paxillin proteins were not affected. Near term, BM proteins
      from gravid horn myometrium demonstrated increased extracellular immunostaining
      and major rearrangement from sporadic protein distribution to organized,
      continuous, and regular structures surrounding the plasma membrane of each
      myocyte. Examination of FA proteins revealed that paxillin was translocated from
      the cytoplasm to the cell periphery, while vinculin was sequestered specifically
      to FAs. At labor, BM and FA proteins, organized in similar bead-like structures,
      were localized on opposing sides of SMC plasma membrane into 2 different
      compartments. We suggest that these stretch-induced changes facilitate formation
      of stable cell-matrix adhesions and provide the molecular basis for optimal force
      transduction during labor contractions.

PMID- 19602723
TI  - The effect of progesterone on myometrial contractility, potassium channels, and
      tocolytic efficacy.
AB  - OBJECTIVES: Recent clinical trials have demonstrated a beneficial effect of
      supplementation with progesterone to prevent preterm labor. We aimed to determine
      the effects of progesterone treatment in vitro and in vivo and 17alpha
      hydroxyprogesterone caproate (17OHPC) in vitro on myometrial contractions.
      METHODS: Myometrial strips were taken from women undergoing cesarean delivery at
      term. We also obtained myometrial biopsies from women participating in a clinical
      trial of progesterone to prevent preterm labor in twins (STOPPIT). After
      establishment of spontaneous contractions, strips were exposed to progesterone or
      17OHPC. Separate strips were exposed to oxytocin and tocolytics alone and in
      combination with progesterone. Potassium channel blockers were added in
      conjunction with progesterone. STOPPIT samples were used to compare the effects
      of in vivo progesterone and placebo. We measured amplitude, frequency and
      activity integral of contractions. RESULTS: Maximum inhibition of contraction
      amplitude was 93 +/- 2% and 67 +/- 14% for progesterone at 30 microM and vehicle
      (70% ethanol), respectively, P < 0.05. 17OHPC did not exert an inhibitory effect.
      Water soluble progesterone exerted a maximal inhibitory effect on amplitude of
      contractions of 82 +/- 10% at 100 microM, P < 0.05. The inhibitory effect of
      progesterone was unaffected by potassium channel blockers. There was no
      difference between in vivo placebo and progesterone-treated groups in either
      amplitude or frequency of contractions, nor was there any difference in the
      response to oxytocin or the tocolytic drugs. CONCLUSIONS: Progesterone exerts
      rapid inhibition of the amplitude of myometrial contractions in vitro but 17OHPC
      does not. The action of progesterone does not appear to operate via potassium
      channels nor does it enhance the activity of certain tocolytic drugs.

PMID- 19602724
TI  - Clostridium botulinum toxin A inhibits contractility in pregnant human myometrium
      in vitro.
AB  - Studies were undertaken to evaluate the effect of Botulinum neurotoxin type-A
      (BoNTA) preparation on oxytocin-induced contractions of pregnant human myometrium
      in vitro. Human myometrial tissue was exposed to increasing concentrations (1-50
      000 U/mL) of BoNT/A. Isometric contractions were measured using a force
      displacement transducer. The cumulative effect of BoNT/A on myometrial activity
      (time to half relaxation [TTR50], frequency, and amplitude) was evaluated. The
      frequency of myometrial contractions was depressed by 40% from baseline (P < .05)
      and relaxation time was increased by 30% (P < .05) from baseline within a narrow
      range of concentrations. There was no significant difference in amplitude. The
      observed effects were rapidly reversed after complete wash out of the tissue.
      BoNT/A or its analogues with more specific tissue affinity may be of value as
      future agents for prevention of unwanted uterine contractile activity associated
      with preterm labor and fetal surgery.

PMID- 19602720
TI  - Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly
      hypertensive patients with previous myocardial infarction from the China Coronary
      Secondary Prevention Study (CCSPS).
AB  - Coronary heart disease, hypertension, and dyslipidemia are highly prevalent and
      commonly coexist in people who are middle-aged and older. Previous data suggested
      that lowering cholesterol concentrations in individuals at high risk of
      cardiovascular disease improved clinical outcomes. Xuezhikang, a partial extract
      of red yeast rice containing statin, has a marked impact on lipids. The purpose
      of this study, therefore, was to evaluate the impact of Xuezhikang on reducing
      cardiovascular events and mortality in elderly Chinese hypertensive patients with
      a history of myocardial infarction (MI) enrolled in the Chinese Coronary
      Secondary Prevention Study. In this randomized trial, 1530 elderly hypertensive
      patients (> or = 65-years-old) with previous MI were assigned either to placebo
      (n = 758) or to Xuezhikang (n = 772) daily for an average of 4.5 years. The
      primary endpoint was recurrent coronary events; the secondary endpoint was all
      cause mortality and other clinical events, including adverse effects. There were
      68 cases of coronary events (8.8%) detected in the Xuezhikang group and 108 cases
      (14.3%) in the placebo group (38.2% risk reduction by Xuezhikang therapy). Death
      from coronary heart disease (CHD) totaled 49 cases in the Xuezhikang group (6.4%)
      and 68 cases in the placebo group (9.0%), indicating that Xuezhikang
      significantly decreased the risk of CHD death by 29.2%. Our study demonstrated
      that Xuezhikang therapy could effectively and safely reduce cardiovascular events
      and all-cause death in Chinese elderly hypertensive patients with previous MI.
      This finding may have an important implication for the treatment of elderly
      hypertensive patients with CHD.

PMID- 19602725
TI  - Critical role of nuclear calcium/calmodulin-dependent protein kinase IIdeltaB in
      cardiomyocyte survival in cardiomyopathy.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in
      cardiac contractility and heart disease. However, the specific role of
      alternatively spliced variants of CaMKII in cardiac disease and apoptosis remains
      poorly explored. Here we report that the deltaB subunit of CaMKII (CaMKIIdeltaB),
      which is the predominant nuclear isoform of calcium/calmodulin-dependent protein
      kinases in heart muscle, acts as an anti-apoptotic factor and is a novel target
      of the antineoplastic and cardiomyopathic drug doxorubicin (Dox (adriamycin)).
      Hearts of rats that develop cardiomyopathy following chronic treatment with Dox
      also show down-regulation of CaMKIIdeltaB mRNA, which correlates with decreased
      cardiac function in vivo, reduced expression of sarcomeric proteins, and
      increased tissue damage associated with Dox cardiotoxicity. Overexpression of
      CaMKIIdeltaB in primary cardiac cells inhibits Dox-mediated apoptosis and
      prevents the loss of the anti-apoptotic protein Bcl-2. Specific silencing of
      CaMKIIdeltaB by small interfering RNA prevents the formation of organized
      sarcomeres and decreases the expression of Bcl-2, which all mimic the effect of
      Dox. CaMKIIdeltaB is required for GATA-4-mediated co-activation and binding to
      the Bcl-2 promoter. These results reveal that CaMKIIdeltaB plays an essential
      role in cardiomyocyte survival and provide a mechanism for the protective role of
      CaMKIIdeltaB. These results suggest that selective targeting of CaMKII in the
      nuclear compartment might represent a strategy to regulate cardiac apoptosis and
      to reduce Dox-mediated cardiotoxicity.

PMID- 19602727
TI  - Amyloidogenic potential of transthyretin variants: insights from structural and
      computational analyses.
AB  - Human transthyretin (TTR) is an amyloidogenic protein whose mild amyloidogenicity
      is enhanced by many point mutations affecting considerably the amyloid disease
      phenotype. To ascertain whether the high amyloidogenic potential of TTR variants
      may be explained on the basis of the conformational change hypothesis, an aim of
      this work was to determine structural alterations for five amyloidogenic TTR
      variants crystallized under native and/or destabilizing (moderately acidic pH)
      conditions. While at acidic pH structural changes may be more significant because
      of a higher local protein flexibility, only limited alterations, possibly
      representing early events associated with protein destabilization, are generally
      induced by mutations. This study was also aimed at establishing to what extent
      wild-type TTR and its amyloidogenic variants are intrinsically prone to beta
      aggregation. We report the results of a computational analysis predicting that
      wild-type TTR possesses a very high intrinsic beta-aggregation propensity which
      is on average not enhanced by amyloidogenic mutations. However, when located in
      beta-strands, most of these mutations are predicted to destabilize the native
      beta-structure. The analysis also shows that rat and murine TTR have a lower
      intrinsic beta-aggregation propensity and a similar native beta-structure
      stability compared with human TTR. This result is consistent with the lack of in
      vitro amyloidogenicity found for both murine and rat TTR. Collectively, the
      results of this study support the notion that the high amyloidogenic potential of
      human pathogenic TTR variants is determined by the destabilization of their
      native structures, rather than by a higher intrinsic beta-aggregation propensity.

PMID- 19602726
TI  - Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate
      CD4(+)CD25(-) T cells and T regulatory cells.
AB  - CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of
      self-tolerance and immune suppression, although the mechanisms controlling T reg
      development and suppressor function remain incompletely understood. Herein, we
      provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an
      important regulator of T regulatory cell suppressor function and CD4(+)CD25(-) T
      cell activation through distinct mechanisms involving transforming growth factor
      (TGF)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both
      TGF-beta1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1
      marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10(-/-)
      CD4(+)CD25(-) T cells have enhanced differentiation along both Th1 and Th2
      pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore,
      KLF10(-/-) CD4(+)CD25(-) T cell effectors cannot be appropriately suppressed by
      wild-type T regs. Surprisingly, KLF10(-/-) T reg cells have reduced suppressor
      function, independent of Foxp3 expression, with decreased expression and
      elaboration of TGF-beta1, an effect completely rescued by exogenous treatment
      with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1,
      KLF10 can transactivate both TGF-beta1 and Foxp3 promoters, implicating KLF10 in
      a positive feedback loop that may promote cell-intrinsic control of T cell
      activation. Finally, KLF10(-/-) CD4(+)CD25(-) T cells promoted atherosclerosis by
      approximately 2-fold in ApoE(-/-)/scid/scid mice with increased leukocyte
      accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical
      regulator in the transcriptional network controlling TGF-beta1 in both
      CD4(+)CD25(-) T cells and T regs and plays an important role in regulating
      atherosclerotic lesion formation in mice.

PMID- 19602728
TI  - Gangliosides as high affinity receptors for tetanus neurotoxin.
AB  - Tetanus neurotoxin (TeNT) is an exotoxin produced by Clostridium tetani that
      causes paralytic death to hundreds of thousands of humans annually. TeNT cleaves
      vesicle-associated membrane protein-2, which inhibits neurotransmitter release in
      the central nervous system to elicit spastic paralysis, but the molecular basis
      for TeNT entry into neurons remains unclear. TeNT is a approximately 150-kDa
      protein that has AB structure-function properties; the A domain is a zinc
      metalloprotease, and the B domain encodes a translocation domain and C-terminal
      receptor-binding domain (HCR/T). Earlier studies showed that HCR/T bound
      gangliosides via two carbohydrate-binding sites, termed the lactose-binding site
      (the "W" pocket) and the sialic acid-binding site (the "R" pocket). Here we
      report that TeNT high affinity binding to neurons is mediated solely by
      gangliosides. Glycan array and solid phase binding analyses identified
      gangliosides that bound exclusively to either the W pocket or the R pocket of
      TeNT; GM1a bound to the W pocket, and GD3 bound to the R pocket. Using these
      gangliosides and mutated forms of HCR/T that lacked one or both carbohydrate
      binding pocket, gangliosides binding to both of the W and R pockets were shown to
      be necessary for high affinity binding to neuronal and non-neuronal cells. The
      crystal structure of a ternary complex of HCR/T with sugar components of two
      gangliosides bound to the W and R supported the binding of gangliosides to both
      carbohydrate pockets. These data show that gangliosides are functional dual
      receptors for TeNT.

PMID- 19602729
TI  - Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in
      stimulating the human femoral nerve.
AB  - This study describes the stability and selectivity of four-contact spiral nerve
      cuff electrodes implanted bilaterally on distal branches of the femoral nerves of
      a human volunteer with spinal cord injury as part of a neuroprosthesis for
      standing and transfers. Stimulation charge threshold, the minimum charge required
      to elicit a visible muscle contraction, was consistent and low (mean threshold
      charge at 63 weeks post-implantation: 23.3 +/- 8.5 nC) for all nerve-cuff
      electrode contacts over 63 weeks after implantation, indicating a stable
      interface with the peripheral nervous system. The ability of individual nerve
      cuff electrode contacts to selectively stimulate separate components of the
      femoral nerve to activate individual heads of the quadriceps was assessed with
      fine-wire intramuscular electromyography while measuring isometric twitch knee
      extension moment. Six of eight electrode contacts could selectively activate one
      head of the quadriceps while selectively excluding others to produce maximum
      twitch responses of between 3.8 and 8.1 N m. The relationship between isometric
      twitch and tetanic knee extension moment was quantified, and selective twitch
      muscle responses scaled to between 15 and 35 N m in tetanic response to pulse
      trains with similar stimulation parameters. These results suggest that this nerve
      cuff electrode can be an effective and chronically stable tool for selectively
      stimulating distal nerve branches in the lower extremities for neuroprosthetic
      applications.

PMID- 19602732
TI  - Therapeutic hypothermia after cardiac arrest during surgery: a meaningful
      pursuit?

PMID- 19602731
TI  - Visual modifications on the P300 speller BCI paradigm.
AB  - The best known P300 speller brain-computer interface (BCI) paradigm is the
      Farwell and Donchin paradigm. In this paper, various changes to the visual
      aspects of this protocol are explored as well as their effects on classification.
      Changes to the dimensions of the symbols, the distance between the symbols and
      the colours used were tested. The purpose of the present work was not to achieve
      the highest possible accuracy results, but to ascertain whether these simple
      modifications to the visual protocol will provide classification differences
      between them and what these differences will be. Eight subjects were used, with
      each subject carrying out a total of six different experiments. In each
      experiment, the user spelt a total of 39 characters. Two types of classifiers
      were trained and tested to determine whether the results were classifier
      dependant. These were a support vector machine (SVM) with a radial basis function
      (RBF) kernel and Fisher's linear discriminant (FLD). The single-trial
      classification results and multiple-trial classification results were recorded
      and compared. Although no visual protocol was the best for all subjects, the best
      performances, across both classifiers, were obtained with the white background
      (WB) visual protocol. The worst performance was obtained with the small symbol
      size (SSS) visual protocol.

PMID- 19602730
TI  - Seizure entrainment with polarizing low-frequency electric fields in a chronic
      animal epilepsy model.
AB  - Neural activity can be modulated by applying a polarizing low-frequency (<<100
      Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF
      stimulation has a graded, modulatory effect on neuronal excitability, and permits
      the simultaneous recording of neuronal activity during stimulation suitable for
      continuous feedback control. We tested a prototype system that allows for
      simultaneous PLEF stimulation with minimal recording artifact in a chronic
      tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous
      seizures. Depth electrode local field potentials recorded during seizures
      revealed a characteristic pattern of field postsynaptic potentials (fPSPs).
      Sinusoidal voltage-controlled PLEF stimulation (0.5-25 Hz) was applied in open
      loop cycles radially across the CA3 of ventral hippocampus. For stimulated
      seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical
      significance of entrainment was assessed with Thomson's harmonic F-test, with
      45/132 stimulated seizures in four animals individually demonstrating significant
      entrainment (p < 0.04). Significant entrainment for multiple presentations at the
      same frequency (p < 0.01) was observed in three of four animals in 42/64
      stimulated seizures. This is the first demonstration in chronically implanted
      freely behaving animals of PLEF modulation of neural activity with simultaneous
      recording.

PMID- 19602733
TI  - Brain, cardiopulmonary bypass and temperature: what should we be doing?

PMID- 19602734
TI  - A comparison of the effects of desflurane, sevoflurane and propofol on QT, QTc,
      and P dispersion on ECG.
AB  - The aim of this prospective, randomized, and double-blinded study was to compare
      the effects of desflurane, sevoflurane, propofol on both atrial and ventricular
      wall function by measurement of QT dispersion (QTd), corrected QT dispersion
      (QTcd), and P dispersion (Pd) on electrocardiogram (ECG). Forty-six patients from
      the American Society of Anesthesiologists class I-II undergoing noncardiac
      surgery, were enrolled in this study. Patients were randomly allocated to receive
      desflurane, sevoflurane or propofol anesthesia. ECG recordings were taken before
      and after 5 minutes of drug administration. Induction with desflurane
      significantly increased the QTd compared to baseline (38 +/- 2 ms vs. 62 +/- 6
      ms, P 0.05). Sevoflurane and propofol anesthesia was not associated with any
      changes in QTd. QTcd was increased with desflurane induction and decreased with
      sevoflurane and propofol induction, but this decrease was only significant in the
      propofol group (67 +/- 5 ms vs. 45 +/- 3 ms, P 0.05). Pd was significantly
      increased after induction with desflurane (34 +/- 3 vs. 63 +/- 6 ms, P 0.05).
      There was a significant increase in QTd and Pd in desflurane group, but this
      increment did not cause any dangerous arrhythmias. QTcd significantly decreased
      in propofol group. We believe that further investigations are required for using
      desflurane as safe as sevoflurane and propofol in noncardiac surgery patients who
      have high cardiac arrhythmia and ischemia risk.

PMID- 19602735
TI  - Treating myocardial stunning randomly, with either propofol or isoflurane
      following transient coronary occlusion and reperfusion in pigs.
AB  - Propofol and isoflurane may be used during fast track anesthesia for off-pump
      bypass, where transient ischemia is common. The purpose of this study was to
      compare the effects of propofol vs isoflurane in a porcine model of acute
      coronary occlusion. Twenty five pigs were randomized to receive general
      anesthesia with either isoflurane, 1 MAC (n = 13), or propofol, 3 mg/kg bolus
      followed by 200 microg/ kg/min infusion (n = 12). Pressure-tipped catheters were
      placed in the left ventricle (LV) and carotid artery; cardiac output was measured
      by ultrasound; two pairs of ultrasonic dimension catheters were placed in the
      subendocardium of LV. The slope of LV end-systolic pressure-volume relationship
      (Emax) was calculated. Reversible ischemia for 15 mins was accomplished with an
      occluder around the left anterior descending artery followed by reperfusion
      period. Measurements were done at baseline, end ischemia, early (5 min) and late
      (30 min) reperfusion. The data collected included systemic hemodynamics, LV end
      diastolic pressure (LVEDP), dP/dt, Emax, and the presence of ventricular
      arrhythmias. The number of animals studied to completion was 19 (n = 11 in the
      isoflurane group; n = 8 in propofol group). There was a significant difference in
      Emax between isoflurane and propofol during early and late reperfusion [3.4 (0.5)
      and 4.0 (0.3) vs 2.6 (0.4) and 3.2 (0.5) mmHg/sec, respectively; P < 0.05].
      Postreperfusion ventricular fibrillation occurred in 54% animals in the propofol
      group vs none in the isoflurane group ( P 0.05). Isoflurane administration was
      found to be cardioprotective against ventricular depression and arrhythmias
      compared to propofol.

PMID- 19602736
TI  - Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in
      continuous renal replacement therapy with calcium-free replacement solution.
AB  - Regional citrate anti-coagulation for continuous renal replacement therapy
      chelates calcium to produce the anti- coagulation effect. We hypothesise that a
      calcium-free replacement solution will require less citrate and produce fewer
      metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a
      tertiary teaching hospital (25 in each group), received continuous venovenous
      hemofiltration using either calcium-containing or calcium-free replacement
      solutions. Both groups had no significant differences in filter life, metabolic
      alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients
      using calcium-containing solution developed metabolic alkalosis earlier, compared
      to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2
      hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was
      used, more citrate was required (mean 280 ml/h, CI 227.2-332.8 vs. 265 ml/h, CI
      203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2
      21.2 vs 51.6 ml/h, CI 26.8-76.4, P < or = 0.0001).

PMID- 19602737
TI  - Pre-operative high sensitive C-reactive protein predicts cardiovascular events
      after coronary artery bypass grafting surgery: a prospective observational study.
AB  - C-reactive protein is a powerful independent predictor of cardiovascular events
      in patients with coronary artery disease. The relation between C-reactive protein
      (CRP) concentration and in-hospital outcome, after coronary artery bypass
      grafting (CABG), has not yet been established. The study aims to evaluate the
      predictive value of pre-operative CRP for in-hospital cardiovascular events after
      CABG surgery. High-sensitivity CRP (hs-CRP) levels were measured pre-operatively
      on the day of surgery in 66 patients scheduled for elective on pump CABG surgery.
      Post-operative cardiovascular events such as death from cardiovascular causes,
      ischemic stroke, myocardial damage, myocardial infarction and low output heart
      failure were recorded. During the first 30 days after surgery, 54 patients were
      free from observed events and 14 developed the following cardiovascular events:
      10 (15%) had myocardial damage, four (6%) had low output heart failure and two
      (3%) suffered stroke. No patients died during the follow-up period. Serum
      concentration of hs-CRP > or = 3.3 mg/l (cut-off point obtained by ROC analysis)
      was related to higher risk of post-operative cardiovascular events (36% vs 6%, P
      = 0.01), myocardial damage (24% vs 6%, P = 0.04) and low output heart failure
      (12% vs 0%, P = 0.04). Multivariate logistic regression analysis showed that hs
      CRP > or = 3.3 mg/l ( P = 0.002, O.R.: 19.3 (95% confidence interval (CI) 2.9
      128.0)), intra-operative transfusion of red blood cells ( P = 0.04, O.R.: 9.9
      (95% C.I. 1.1-85.5)) and absence of diuretics in daily antihypertensive treatment
      ( P = 0.02, O.R.: 15.1 (95% C.I. 1.4-160.6) were independent predictors of
      combined cardiovascular event. Patients having hs-CRP value greater or equal to
      3.3 mg/l pre-operatively have an increased risk of post-operative cardiovascular
      events after on pump coronary artery bypass grafting surgery.

PMID- 19602738
TI  - Infrarenal abdominal aortic aneurysm repair in presence of coronary artery
      disease: optimization of myocardial stress by controlled phlebotomy.
AB  - The repair of abdominal aortic aneurysm (AAA) in the presence of significant
      coronary artery disease (CAD) carries a high-risk of adverse peri-operative
      cardiac event. The options to reduce cardiac risk include perioperative beta
      blockade, preoperative optimization by myocardial revascularization and
      simultaneous (combined) coronary artery bypass grafting and aneurysm repair. We
      describe intra-operative controlled phlebotomy to optimize myocardial stress
      during repair of infrarenal AAA in a patient with significant stable CAD.

PMID- 19602739
TI  - Delayed presentation of right and left ventricle perforation due to suicidal nail
      gun injury.
AB  - We describe a case of delayed presentation of attempted suicide with a nail gun
      that penetrated both the right and left ventricle. Nearly invisible entry point
      of the nail did not reflect the gravity of the injury. A prompt and accurate
      history along with chest X-ray and bedside transthoracic echocardiography
      facilitated localization of the nails and helped assess the damage. Despite
      cardiac arrest after induction of general anesthesia, the patient had a
      successful outcome. Issues related to the injury site, modalities of
      investigation and management strategies in a patient with cardiac tamponade are
      discussed.

PMID- 19602740
TI  - Intra-operative assessment of biventricular function using trans-esophageal
      echocardiography pre/post-pulmonary thromboembolectomy in patient with chronic
      thromboembolic pulmonary hypertension.
AB  - Postoperative studies in patients with chronic thromboembolic pulmonary
      hypertension (CTPH) have shown that pulmonary thromboembolectomy (PTE) results in
      a rapid decrease of right ventricular (RV) size, improvement in the RV systolic
      function and left ventricular (LV) diastolic function. However, the extent to
      which the biventricular function recovers immediately after embolectomy in post
      cardiopulmonary bypass period is not clear. A 45-year-old male patient was
      operated for retrieval of thrombus from pulmonary trunk and right pulmonary
      artery. Intraoperative transesophageal echocardiography (TOE) before surgery
      revealed signs of RV dysfunction and enlargement. The interventricular septum was
      seen moving paradoxically during end-systole and early-diastole. E/A ratio on
      transmitral Doppler flow velocity profile was about 0.63 and S/D ratio on
      pulmonary venous Doppler profile was 2.25, indicative of LV diastolic
      dysfunction. After weaning the patient from bypass, navigation on TOE showed
      marginal recovery of the RV systolic function and abatement of septal paradox to
      some extent. However, significant improvement was observed in the LV diastolic
      parameter (normal E/A ratio, S/D ratio of 1.08). We conclude that the
      geometrically altered LV recovers more than the hypertrophied and hypokinetic RV
      in a patient with CTPH in the post-bypass period.

PMID- 19602741
TI  - Decompression of superior vena cava during bidirectional Glenn shunt.
AB  - Patients undergoing bi-directional Glenn shunt for various congenital anomalies
      of the heart will have their superior vena cava (SVC) clamped during the
      procedure. The duration of the procedure is variable, ranging from five to 30
      minutes. This can affect the cerebral perfusion due to raised venous pressure
      [Cerebral blood flow = Mean arterial pressure-(Intracranial pressure + Central
      venous pressure)]. Shunting away the SVC blood is a well known technique to
      counter this problem, but we describe two cases where a novel technique was
      successfully used to decompress the SVC.

PMID- 19602742
TI  - ST elevation--an indication of reversible neurogenic myocardial dysfunction in
      patients with head injury.
AB  - This report describes a patient who presented with signs of meningitis four days
      after head injury. The patient had ST elevation on electrocardiography along with
      hypotension and positive tropinin T test, mimicking inferior wall infarction. The
      ST changes resolved within 48 hours of intensive care management. Subsequent
      investigations failed to document any myocardial infarction.

PMID- 19602743
TI  - Large pseudoaneurysm of aortic root after aortic valve replacement for rheumatic
      heart disease: a rare complication.

PMID- 19602744
TI  - Endothoracic hemopoiesis: imaging of a rare clinical entity.

PMID- 19602745
TI  - Adult cardiac transplantation: a review of perioperative management (part-II).
AB  - Heart transplant is the definitive therapy for end-stage heart failure. This two
      part review article focussed first on the perioperative management of patients
      for heart transplantation. This part II will be a comprehensive review of the
      current status of mechanical assist device therapy for surgical management of the
      patient with refractory end-stage heart failure.

PMID- 19602746
TI  - Quantification of AS and AR.
AB  - Trans-esophageal echocardiography (TEE) is routinely used in valvular surgery in
      most institutions. The popularity of TEE stems from the fact that it can
      supplement or confirm information gained from other methods of evaluation or make
      completely independent diagnoses. Quantitative and qualitative assessment permits
      informed decisions regarding surgical intervention, type of intervention,
      correction of inadequate surgical repair and re-operation for complications. This
      review summarizes the various methods for quantification of aortic regurgitation
      and stenosis on TEE. The application of Doppler echo (pulsed wave, continuous
      wave and color) with two-dimensional echo allows the complete evaluation of AV
      lesions.

PMID- 19602747
TI  - Intra-operative trans-esophageal echocardiography in congenital heart disease.
AB  - Intra-operative trans-esophageal echocardiography (TEE) is an important
      monitoring and diagnostic tool used during surgery for repair of congenital heart
      disease. In several studies,TEE has been shown to provide additional intra
      cardiac anatomic information. Its ability to be used intra- operatively before
      and after cardiac repair makes it a unique tool. Before TEE was available for
      intra-operative use, significant residual abnormalities were frequently not
      detected. The result was often substantial post-operative morbidity and mortality
      and sometimes the need for re-operation. According to practice guidelines
      established by the Society of Cardiovascular Anesthesiologists and the American
      Society of Anesthesiologists, there is strong evidence for the usefulness of TEE
      in surgery for congenital heart disease because it significantly improves the
      clinical outcome of these patients. Before surgical correction, TEE helps confirm
      diagnosis and spot any additional lesion, while after the surgical correction, it
      provides baseline parameters for comparison after the surgical correction.

PMID- 19602748
TI  - How do I get an optimal image?
AB  - Trans-esophageal echocardiography (TEE) is fast becoming an indispensable
      monitoring and diagnostic modality in cardiac operation rooms. Its convenience
      and dependability in making important and crucial decisions intra-operatively,
      during cardiac operative procedures, makes it one of the most useful weapons in a
      cardiac anesthesiologist's armory. But to make reliable inferences based on intra
      operative TEE, creation and development of a proper image is one of the
      fundamental requirements. The image quality can be affected by factors like
      patient anatomy, quality of the ultrasound system, and skill of the
      echocardiographer. Since the first two cannot be changed, in most of cases, we
      will have to work on the third factor to optimize image quality. A working
      knowledge of the physics of ultrasound imaging and a sufficient familiarity with
      the various knobs and controls on the machine will go a long way in helping one
      acquire an optimum image.

PMID- 19602749
TI  - Trans-esophageal echocardiography for tricuspid and pulmonary valves.
AB  - Transesophageal echocardiography has been shown to provide unique information
      about cardiac anatomy, function, hemodynamics and blood flow and is relatively
      easy to perform with a low risk of complications. Echocardiographic evaluation of
      the tricuspid and pulmonary valves can be achieved with two-dimensional and
      Doppler imaging. Transesophageal echocardiography of these valves is more
      challenging because of their complex structure and their relative distance from
      the esophagus. Two-dimensional echocardiography allows an accurate visualization
      of the cardiac chambers and valves and their motion during the cardiac cycle.
      Doppler echocardiography is the most commonly used diagnostic technique for
      detecting and evaluating valvular regurgitation. The lack of good quality
      evidence makes it difficult to recommend a validated quantitative approach but
      expert consensus recommends a clinically useful qualitative approach. This review
      ennumerates probe placement, recommended cross-sectional views, flow patterns,
      quantitative equations including the clinical approach to the noninvasive
      quantification of both stenotic and regurgitant lesions.

PMID- 19602750
TI  - Trans-esophageal echocardiography in off-pump coronary artery bypass grafting.
AB  - Two features of off-pump coronary artery bypass (OPCAB) can lead to hemodynamic
      instability: transient occlusion of coronary arteries during distal anastomosis
      construction and displacement of the heart to provide access to distal coronary
      arteries. The position of the heart during OPCAB trans-esophageal
      echocardiography (TEE) can often provide an indication as to how much compression
      of the right or left ventricle has occurred. If either chamber is not filling,
      repositioning of the heart will be necessary. Close observation of the heart with
      TEE during periods of coronary occlusion may facilitate detection of worsening
      cardiac function as evidenced by weakening contraction, ventricular dilatation,
      or increasing mitral or tricuspid regurgitation. Haemodynamic changes are more
      pronounced with displacement of the heart to access posterior coronary arteries
      than anterior vessels. Cardiac manipulations during off-pump coronary artery
      bypass grafting (OPCABG) can lead to haemodynamic instability. This, along with
      distal anastomosis causing transient occlusion of coronary arteries, may cause
      transient hypotension with increased filling pressures. TEE is more helpful in
      this scenario. In these patients, TEE helps differentiate between cardiac
      dysfunction and secondary to myocardial ischemia in which regional wall motion
      abnormalities will be present from a much more common scenario where the increase
      in filling pressure is secondary to extra cardiac compression and provides the
      ability to detect mitral regurgitation (MR) with a color-flow Doppler, as well as
      assess right heart function.

PMID- 19602751
TI  - High thoracic epidural analgesia for cardiac surgery: time to move from morbidity
      to quality of recovery indicators.

PMID- 19602752
TI  - Thoracic epidural anesthesia in cardiac surgery--current standing.

PMID- 19602753
TI  - A practical tip: rings of blood for successful radial artery cannulation.

PMID- 19602754
TI  - Intravenous ondansetron causing severe bradycardia: two cases.

PMID- 19602755
TI  - ABO blood groups and myocardial infarction among Palestinians.

PMID- 19602756
TI  - Prognostic factors of acute aluminum phosphide poisoning.
AB  - BACKGROUND: In Morocco, acute aluminum phosphide poisoning (AAlPP) is a serious
      health care problem. It results in high mortality rate despite the progress of
      critical care. AIMS: The present paper aims at determining the characteristics of
      AAlPP and evaluating its severity factors. SETTING AND DESIGN: We studied
      consecutive patients of AAlPP admitted to the medical intensive care unit (ICU)
      (Ibn Sina Hospital, Rabat, Morocco) between January 1992 and December 2007.
      MATERIALS AND METHODS: Around 50 parameters were collected, and a comparison was
      made between survivor and nonsurvivor groups. STATISTICAL ANALYSIS: Data were
      analyzed using Fisher exact test, Mann-Whitney U test and Cox regression model.
      RESULTS: Forty-nine patients were enrolled: 31 females and 18 males; their
      average age was 26+/-11 years. The ingested dose of aluminum phosphide was 1.2+/
      0.7 g. Self-poisoning was observed in 47 cases, and the median of delay before
      admission to the hospital was 5.3 hours (range, 2.9-10 hours). Glasgow coma scale
      was 14+/-2. Shock was reported in 42.6% of the patients. pH was 7.1+/-0.4, and
      bicarbonate concentration was 16.3+/-8.8 mmol/L. Electrocardiogram abnormalities
      were noted in 28 (57%) cases. The mortality rate was 49% (24 cases). The
      prognostic factors were APACHE II (P=0.01), low Glasgow coma scale (P=0.022),
      shock (P=0.0003), electrocardiogram abnormalities (P=0.015), acute renal failure
      (P=0.026), low prothrombin rate (P=0.020), hyperleukocytosis (P=0.004), use of
      vasoactive drugs (P<0.001), use of mechanical ventilation (P=0.003). Multivariate
      analysis by logistic regression revealed that mortality in AAlPP correlated with
      shock (RR=3.82; 95% CI=1.12-13.38; P=0.036) and altered consciousness (RR=3.26;
      95% CI=1.18-8.99; P=0.022). CONCLUSION: AAlPP is responsible for a high
      mortality, which is primarily due to hemodynamic failure.

PMID- 19602757
TI  - Objective standardized clinical assessment with feedback: Adapting the objective
      structured clinical examination for postgraduate psychiatry training in India.
AB  - BACKGROUND: The objective structured clinical examination (OSCE) is used commonly
      for assessment of psychiatry trainees but has been used less for teaching. AIM
      AND SETTING: This study describes the adaptation of the OSCE method for training
      purposes in a postgraduate psychiatry training center in India and the initial
      findings with regard to trainee performance. MATERIALS AND METHODS: The adapted
      method was called the objective structured clinical assessment with feedback
      (OSCAF). The adaptation included several steps--modifying existing OSCE patterns
      for language and cultural appropriateness, using supervised roleplaying instead
      of standardized or simulated patients and evolving an assessment method (14-item
      checklist) that would generate feedback. This exercise was conducted in front of
      a group of multidisciplinary peers and supervisors. STATISTICAL ANALYSIS:
      Descriptive statistics and ANOVA were used. RESULTS: Analysis of the performance
      based on the 14-item checklist assessing common elements of any patient-related
      interaction in 34 different OSCAF tasks indicated the following: less-than
      satisfactory (<75%) performances in the following areas--assuring confidentiality
      (73.5%), assessing comfort (62%), summarizing (60%), closure (62%) and checking
      whether the 'patient' had understood what was being communicated (42%). Based on
      the nature of clinical situations, performances on some specific and difficult
      OSCAF situations were found to be inadequate and indicated need for further
      training. CONCLUSIONS: We have been able to demonstrate OSCAF to be a convenient,
      cost-effective training method in psychiatry, with limited demands on resources;
      however, further refinements in ratings and feedback methods and studies on
      effectiveness may enhance its utility.

PMID- 19602758
TI  - Comparison of efficacy of oral drotaverine plus mefenamic acid with paracervical
      block and with intravenous sedation for pain relief during hysteroscopy and
      endometrial biopsy.
AB  - BACKGROUND: Office hysteroscopy with endometrial biopsy is usually the first
      investigation for abnormal uterine bleeding and other uterine diseases. AIMS: To
      evaluate the effect of oral drotaverine with mefenamic acid on pain perception
      during hysteroscopy and endometrial biopsy and to compare it with that of
      paracervical block using 1% lignocaine and with that of intravenous sedation
      using diazepam with pentazocine. SETTINGS AND DESIGN: Outpatient gynecological
      department and open randomized trial. MATERIALS AND METHODS: One hundred twenty
      women undergoing hysteroscopy and endometrial biopsy were randomized into 3
      groups. Group I received tablet containing drotaverine hydrochloride (80
      mg)+mefenamic acid (250 mg), group II received lignocaine paracervically and
      group III received intravenous diazepam. The intensity of pain during the
      procedure, 30 and 60 minutes later on visual analog scale (VAS) was assessed.
      STATISTICAL ANALYSIS: Statistical analysis was performed using Kruskal-Wallis
      test, with the Bonferroni correction, the t test, and the chi2 test. RESULTS:
      Groups were similar in age, parity, vaginal birth or relevant medical history. A
      statistically significant difference in pain scores was noted among the 3 groups
      during the procedure (group I, 4.13+/-1.28; group II, 5.93+/-1.26; group III,
      5.58+/-1.51), (P<0.001); as well as 30 minutes later (group I, 1.78+/-0.89; group
      II, 2.53+/-0.81; group III, 2.23+/-0.94), (P<0.001) and 60 minutes later (group
      I, 1.2+/-0.46; group II, 1.98+/-0.83; group III, 1.68+/-0.75), (P<0.001). VAS at
      different time intervals among the groups was also statistically significant. No
      adverse effects were observed. CONCLUSIONS: Oral drotaverine with mefenamic acid
      is effective in women undergoing hysteroscopy and endometrial biopsy.

PMID- 19602760
TI  - Microangiopathic hemolytic anemia following disseminated intravascular
      coagulation in aluminum phosphide poisoning.

PMID- 19602759
TI  - Aspergillus endophthalmitis in orthotopic liver transplantation.
AB  - In this report, we describe a patient with drug-induced liver failure who
      developed endogenous endophthalmitis after liver transplantation. Our patient's
      clinical course was so fulminant that the eye was lost in less than 1 month,
      without any response to therapy. Recognition of this infection is important
      because many patients die of disseminated Aspergillus infection, which may be
      detected early with bedside funduscopic examination by an ophthalmologist.
      Probably if the patient had referred to us earlier, it may have been possible to
      save the eye.

PMID- 19602761
TI  - Recurrent hematospermia due to aspirin.

PMID- 19602762
TI  - Reporting ethical processes: survey of 'instructions to authors' provided by
      Indian journals.

PMID- 19602763
TI  - Ragging: a public health problem in India.
AB  - Ragging is any disorderly conduct that has the effect of teasing or handling with
      rudeness any student, which causes or is likely to cause annoyance, harm or to
      raise fear in a junior so as to adversely affect the psyche of the junior.
      Ragging is practiced all over the world, with different nomenclature like hazing,
      fagging; bapteme in French; doop in Dutch; and Mopokaste in Finnish. The first
      recorded cases of ragging were in the 8th century BC during the Olympics in
      Greece. Ragging has been frequently associated with a broad spectrum of physical,
      behavioral, emotional and social problems among the victims. It independently
      increases suicide risks. Some of the reasons given by students for ragging are
      they were also ragged by their seniors; sense of superiority; and introduction.
      Other factors perpetuating ragging are use of alcohol in hostels and lack of
      implementation of serious anti-ragging measures by college authorities. Various
      practical steps to control ragging must include strict role of authorities, ban
      on alcohol within college and hostels, surprise raids in hostels at night,
      postings (with accommodation) of wardens in hostels, separate hostels for
      juniors, presence of college "disciplinary committee" and "cultural committee,"
      strict punishments for those involved in ragging, actions by Medical Council of
      India (MCI) and University Grants Commission (UGC) against the erring colleges
      and universities and formulation of anti-ragging laws. Ragging should be declared
      a public health problem because it involves the physical, mental and social
      exploitation of not only an individual but also of his/her family and the society
      as a whole.

PMID- 19602764
TI  - Personal listening devices and hearing loss: seeking evidence of a long term
      problem through a successful short-term investigation.

PMID- 19602766
TI  - Heavy metals and noise exposure: health effects.
AB  - Heavy metals are chemical elements with a specific gravity that is atleast five
      times that of water which is 1 at 4 degrees C. The commonly encountered heavy
      metals are lead,mercury, cadmium, and arsenic. Lead levels in children continue
      to be a health hazard as the current limit of 10 ug/dL is considered too high
      with the WHO estimate of 40% of children having blood levels greater than 5
      ug/dL. Some authors have suggested a new limit should be set at 2 ug/dL. There
      are substantial differences in the literature regarding the effects of lead on
      hearing as assessed by pure tone audiometry. Mercury causes hearing loss and
      neurological dysfunction in Humans and animals. Methyl mercury is considered a
      more toxic compound to mercuric chloride. Cadmium causes a range of health
      effects from lung cancer, kidney damage to hearing loss. Dose dependent effects
      on hearing loss have been shown in rats. Combined effect with noise exposure has
      been shown to be more pronounced. Arsenic is released into the environment
      through the smelting process of copper, zinc, and lead. It is usually found in
      the water supply. Hearing impairments have been noted in the low and high
      frequencies in conjunction with balance disturbance.

PMID- 19602765
TI  - Output sound pressure levels of personal music systems and their effect on
      hearing.
AB  - This study looked at output levels produced by new generation personal music
      systems (PMS), at the level of eardrum by placing the probe microphone in the ear
      canal. Further, the effect of these PMS on hearing was evaluated by comparing the
      distortion product otoacoustic emissions and high frequency pure tone thresholds
      (from 3 kHz to 12 kHz) of individuals who use PMS to that of age matched controls
      who did not use PMS. The relationship between output sound pressure levels and
      hearing measures was also evaluated. In Phase I output SPLs produced by the PMS
      were measured in three different conditions - a) at volume control setting that
      was preferred by the subjects in quiet b) at volume control setting that was
      preferred by the subject in presence of 65 dB SPL bus noise c) at maximum volume
      control settings of the instrument. In Phase II pure tone hearing thresholds and
      DPOAEs were measured. About 30% of individuals in a group of 70 young adults
      listened to music above the safety limits (80 dBA for 8 hours) prescribed by
      Ministry of Environment and Forests, India. Addition of bus noise did not
      increase the preferred volume control settings of the subjects significantly.
      There were no significant differences between the experimental and control groups
      for mean pure tone threshold and for mean DPOAE amplitude comparisons. However, a
      positive correlation between hearing thresholds and music levels and a negative
      correlation between DPOAE measures and music levels were found.

PMID- 19602767
TI  - Assessment of noise exposure in a hospital kitchen.
AB  - In March 2007, the National Institute for Occupational Safety and Health (NIOSH)
      was asked to evaluate the noise exposure of employees in the Nutrition and Food
      Services Department of a large hospital, because of noise concerns raised after
      the installation of the PowerSoak dishwashing system. Eleven employees (two
      cooks, eight food service workers, and a materials handler) contributed 13 full
      shift and two task-based personal noise dosimetry measures over two days. The
      noise levels for two food service workers assigned to the pots and pans room
      (85.1 and 85.2dBA), a cook working in the food preparation area (85.9 dBA), and a
      food service worker assigned to the dishwashing room (89.5 dBA) exceeded the
      NIOSH Recommended Exposure Limit (REL); however, none of the measures exceeded
      the Occupational Safety and Health Administration (OSHA) Permissible Exposure
      Limit (PEL). The noise level from the PowerSoak dishwashing system alone was not
      excessive, but additional noise from the food preparation area (primarily from
      blenders and utensils), and from metal-to-metal contact between stainless steel
      pots and pans and metal racks, may explain exposures above the NIOSH REL for
      employees in the pots and pans room. The cooks were exposed to many intermittent
      impact noise sources, such as, metal-to-metal contact between utensils and the
      use of industrial-size blenders. We recommended that metal-to-metal contact be
      reduced as much as possible throughout the Nutrition and Food Services
      Department, and hearing protectors be provided to employees in the dishwashing
      room until engineering controls were in place.

PMID- 19602768
TI  - Is there evidence that environmental noise is immunotoxic?
AB  - Noise is a stressor. Noise-induced stress can lead to release of stress hormones.
      Acute stress whether physical or psychological is necessary for adaptation to
      change. However, chronic stress can lead to the persistent elevation of
      hypothalamic-pituitary-adrenocortical hormones, which are detrimental to health
      and can lead to disease states. It has also been suggested that there may be
      multiple interactions between the sympathetic and the complex feedback
      neuroendocrine systems, which interact with the immune system, in the genesis of
      the observed effects. Thus noise stress may be a factor contributing to the
      mechanisms of noise-induced hearing loss through alterations in the cell-mediated
      immune response. Other than the noise stress acting directly, it may also have an
      impact on the immune function via noise-induced sleep deprivation. Furthermore,
      recent evidence indicates that the immune function may be modified by
      conditioning techniques, perceived control, or the individual's ability to cope
      with stress-inducing factors. This suggests a possible means of alleviating the
      stress-induced effects. This review will examine the current available data on
      the effects of chronic environmental noise exposure on immune function.

PMID- 19602769
TI  - Could an underlying hearing loss be a significant factor in the handicap caused
      by tinnitus?
AB  - There have been several studies that have demonstrated a link between the hearing
      loss of subjects and tinnitus. However, there has been no systematic evaluation
      of the link between perceived tinnitus distress and an underlying hearing loss.
      The purpose of the current study is to explore this association, and ascertain
      whether a subject's hearing loss contributes to the handicap caused by tinnitus.
      A group of 96 adults were evaluated with Pure Tone Audiometry and a questionnaire
      that included the Tinnitus Handicap Inventory (THI). In 58% of the subjects, the
      side of the unilateral or worse tinnitus corresponded with the ear with poorer
      hearing thresholds. A subset of the THI, the Two Question Mean (TQM) that was
      related to questions with regard to communication, correlated significantly with
      the hearing thresholds in the better hearing ear ( P < 0.01). There was also a
      significant correlation between the THI and TQM scores ( P < 0.01). These results
      suggested that in tinnitus subjects with impaired hearing, the underlying hearing
      loss may be a significant factor in the perceived distress.

PMID- 19602770
TI  - Exposure-response relationship of the association between aircraft noise and the
      risk of hypertension.
AB  - Noise is a stressor that affects the autonomic nervous system and the endocrine
      system. Under conditions of chronic noise stress the cardiovascular system may
      adversely be affected. Epidemiological noise studies regarding the relationship
      between aircraft noise and cardiovascular effects have been carried out on adults
      and on children focussing on mean blood pressure, hypertension and ischemic heart
      diseases as cardiovascular endpoints. While there is evidence that road traffic
      noise increases the risk of ischemic heart disease, including myocardial
      infarction, there is less such evidence for such an association with aircraft
      noise. This is partly due to the fact that large scale clinical studies are
      missing. There is sufficient qualitative evidence, however, that aircraft noise
      increases the risk of hypertension in adults. Regarding aircraft noise and
      children's blood pressure the results are still inconsistent. The available
      literature was evaluated for the WHO working group on "Aircraft Noise and Health"
      based on the experts' comprehensive knowledge in this field. With respect to the
      needs of a quantitative risk assessment for burden of disease calculations an
      attempt was made to derive an exposure-response relationship based on a meta
      analysis. This association must be viewed as preliminary due to limitations which
      are concerned with the pooling of studies due to methodological differences in
      the assessment of exposure and outcome between studies. More studies are needed
      to establish better estimates of the risk.

PMID- 19602771
TI  - Reduction of road traffic noise and mental health: an intervention study.
AB  - Road traffic noise exposure leads to annoyance and impairment of quality of life
      and may impair health. If this association is causal, a reduction in noise
      exposure should result in a reduction in noise annoyance and improvement in
      quality of life. This study examines whether the reduction in road traffic noise
      following the introduction of a bypass leads to reduction in noise annoyance and
      common mental disorder and an improvement in quality of life. Repeated measures
      field study with intervention in three small towns in North Wales, UK.
      Participants were residents 16 to 90 years living in areas of high or low
      exposure to road traffic noise. At baseline there was no difference in annoyance,
      quality of life or common mental disorder between traffic noise exposed and quiet
      areas. There was a small reduction in noise exposure (2-4 dBA) with the opening
      of the bypass. There was no reduction in noise annoyance and no change in levels
      of common mental disorder and quality of life following the introduction of the
      bypass. Traffic noise reduction associated with the introduction of the bypass
      was not associated with measurable changes in quality of life or common mental
      disorder. This study suggests that reduction in traffic noise level of 3dB or
      less is insufficient to influence annoyance or mental health. However, the
      methodological difficulties of the study limit the conclusions that can be drawn
      on whether there is a causal effect of noise on common mental disorder.

PMID- 19602772
TI  - Non-auditory health effects among air force crew chiefs exposed to high level
      sound.
AB  - The possibility of non-auditory health effects in connection with occupational
      exposure to high level sound is supposed by some researchers, but is still
      debated. Crew chiefs on airfields are exposed to high-level aircraft sound when
      working close to aircraft with running engines. We compared their health status
      with a similar control group who were not subject to this specific sound
      exposure. Health records of 42 crew chiefs were compared to health records of 42
      aircraft mechanics and 17 former crew chiefs. The specific sound exposure of crew
      chiefs was assessed. The number of reported disease cases was generally small,
      but generally slightly higher among mechanics than among crew chiefs. Diseases of
      the ear were more frequent among crew chiefs (not significant). Former crew
      chiefs reported fewer diseases of the ear and more airways infections (both
      significant). The sound exposure during launch was up to 144 dB (peak) and 124 dB
      (L(eq) ), but for limited time. The study did not reveal a higher disease
      frequency in general among crew chiefs. However, it did reveal a tendency to ear
      diseases, possibly due to their exposure to high-level sound.

PMID- 19602774
TI  - High-normal blood pressure and the risk of cardiovascular disease.
AB  - The guidelines of the Joint National Committee 7 from the USA on hypertension
      have unified the normal and high-normal blood pressure categories into a single
      entity termed ;prehypertension'. In contrast, The European Guidelines for the
      management of hypertension in 2007 considered ;prehypertensive' to be divided
      into normal and high-normal blood pressure. These patients with high-normal blood
      pressure or prehypertension might progress to hypertension over time. Previous
      studies have shown that high-normal blood pressure is a risk factor for
      cardiovascular disease (CVD) in Western countries and Japan. The combination of
      high-normal blood pressure and other cardiovascular risk factors increases the
      risks of CVD. Recently, metabolic syndrome has also been shown to be a risk
      factor for CVD. In Japan, the association between metabolic syndrome and CVD was
      also found to be significant. The risks for CVD incidence were similar among
      participants who had the same number of components, regardless of the presence of
      abdominal obesity. In the Japanese guidelines for the management of hypertension
      published in 2009, patients are considered to be in a high-risk group if they
      have diabetes, chronic kidney disease, 3 or more risk factors, target organ
      damage or CVD, even if they have only high-normal blood pressure, and appropriate
      antihypertensive therapy should be initiated.

PMID- 19602775
TI  - Relationship between renal function, aortic stiffness and left ventricular
      function in patients with coronary artery disease.
AB  - BACKGROUND: There are plausible reasons to hypothesize that increased aortic
      stiffness and left ventricular (LV) dysfunction may occur in early renal
      insufficiency. METHODS AND RESULTS: The correlation of glomerular filtration rate
      (GFR) with the augmentation index (AI) of ascending aortic pressure and indices
      of LV systolic and diastolic function (ejection fraction, LV pressure relaxation
      time constant, LV end-diastolic pressure and mitral inflow (E/A) and annular
      velocities (S' and E')) was examined in 359 consecutive patients undergoing
      cardiac catheterization for coronary artery disease (CAD). When patients were
      stratified according to GFR of 60, 75 and 90 ml x min(-1) x 1.73 m(-2), there was
      a progressive increase in AI and decreases in E/A and E' with decreasing GFR.
      There were no linear trends in other indices of systolic or diastolic function
      across GFR groups. After adjustment for potential confounders, reduced GFR was
      associated with increased AI, but not with decreased E/A or E'. CONCLUSIONS:
      Early renal impairment may be partly associated with increased aortic stiffness,
      but not with LV systolic or diastolic function in CAD patients.

PMID- 19602777
TI  - Value of ventricular stiffness index and ventriculoarterial interaction in
      patients with nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Whether echo-Doppler-derived index of ventricular elastance or
      ventriculoarterial interaction can reliably reflect circulatory efficiency in
      various conditions was investigated in the present study and whether they can be
      helpful in predicting exercise capacity in patients with dilated cardiomyopathy
      (DCM). METHODS AND RESULTS: The 25 patients with DCM, 25 age- and gender-matched
      hypertensive patients, and 25 marathon runners underwent symptom-limited graded
      supine bicycle exercise echocardiography after resting echo-Doppler evaluation.
      Echo-Doppler-derived left ventricular (LV) diastolic elastance index (Ed),
      ventricular-vascular coupling index (10 x Ea/Ees), based on arterial elastance
      index (Ea) to LV end-systolic elastance index (Ees), and hemodynamic parameters
      were measured during rest and exercise. DCM patients had lower Ees, higher Ed and
      Ea/Ees with blunted exercise responses of Ees than the other groups, and the
      hypertensive patients had lower Ees and DeltaEes compared with the marathon
      runners. Resting Ed, Ea/Ees, and total stiffness index (10 x Ed x Ea/Ees)
      correlated with exercise duration independent of age and gender. A stiffness
      index of 0.8 could reliably predict impaired exercise capacity. CONCLUSIONS: Echo
      derived elastance is predictive of exercise capacity in patients with DCM.

PMID- 19602776
TI  - Propylthiouracil attenuates monocrotaline-induced pulmonary arterial hypertension
      in rats.
AB  - BACKGROUND: Propylthiouracil (PTU) enhances nitric oxide production and inhibits
      smooth muscle cell proliferation, suggesting a possible role in the prevention of
      pulmonary arterial hypertension (PAH). METHODS AND RESULTS: The 30 male Sprague
      Dawley rats were randomized to receive saline injection only (group 1),
      monocrotaline (MCT) (70 mg/kg) only (group 2) or MCT + 0.1% PTU in drinking water
      (group 3) given on day 5 after MCT administration. By day 35, western blot showed
      lower connexin43 (Cx43) and membranous protein kinase C-epsilon expressions in
      the right ventricle (RV) of group 2 animals than in the other groups (all
      P<0.05). Conversely, Cx43 expression in the lung was higher in group 2 than in
      other groups (all P<0.02). Additionally, mRNA expressions of matrix
      metalloproteinase-9, tissue necrotic factor-alpha, and caspase-3 were higher,
      whereas Bcl-2 and endothelial nitric oxide synthase were lower, in the lungs and
      RV of group 2 rats than in the other groups (all P<0.05). Moreover, the numbers
      of alveolar sacs and lung arterioles were also reduced in group 2 than in other
      groups (all P<0.05), and RV systolic pressure and RV weight were increased in
      group 2 compared with other groups (all P<0.001). CONCLUSIONS: PTU effectively
      attenuates complications associated with MCT-induced PAH.

PMID- 19602779
TI  - [Role of vasopressin receptor in psychological and cognitive functions].

PMID- 19602778
TI  - Treatment with recombinant placental growth factor (PlGF) enhances both
      angiogenesis and arteriogenesis and improves survival after myocardial
      infarction.
AB  - BACKGROUND: Placental growth factor (PlGF), a homolog of vascular endothelial
      growth factor, is reported to stimulate angiogenesis and arteriogenesis in
      pathological conditions. It was recently demonstrated that PlGF is rapidly
      produced in myocardial tissue during acute myocardial infarction (MI). However,
      the effects of exogenous PlGF administration on the healing process after MI are
      not fully understood. The purpose of the present study was to examine whether
      PlGF treatment has therapeutic potential in MI. METHODS AND RESULTS: Recombinant
      human PlGF (rhPlGF: 10 microg) was administered continuously for 3 days in a
      mouse model of acute MI. rhPlGF treatment significantly improved survival rate
      after MI and preserved cardiac function relative to control mice. The numbers of
      CD31-positive cells and alpha-smooth muscle actin-positive vessels in the infarct
      area were significantly increased in the rhPlGF group. Endothelial progenitor
      cells (Flk-1(+)Sca-1(+) cells) were mobilized by rhPlGF into the peripheral
      circulation. Furthermore, rhPlGF promoted the recruitment of GFP-labeled bone
      marrow cells to the infarct area, but only a few of those migrating cells
      differentiated into endothelial cells. CONCLUSIONS: Exogenous PlGF plays an
      important role in healing processes by improving cardiac function and stimulating
      angiogenesis following MI. It can be considered as a new therapeutic molecule.

PMID- 19602780
TI  - [Molecular mechanisms of sustained Ca2+ influx triggerd by G protein-coupled
      receptors].

PMID- 19602781
TI  - [Reduction of autofluorescence of in vivo fluorescence imaging by using purified
      diet].

PMID- 19602782
TI  - [Calcium imaging of multineuron activity in brain slice preparations].

PMID- 19602783
TI  - [BCS strategies at drug discovery and development stages].

PMID- 19602784
TI  - [Pharmacological profiles and clinical effects of recombinant human thyrotropin
      alfa (Thyrogen) Intramuscular Injection 0.9 mg)].

PMID- 19602785
TI  - [Pharmacological and clinical profiles of adapalene (Differin) gel 0.1%].

PMID- 19602786
TI  - The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus
      metformin treatment on adhesion molecules in cases with polycystic ovary syndrome
      (PCOS).
AB  - OBJECTIVE: To determine if EE/CA and EE/CA plus metformin treatment have any
      effect on adhesion molecules in cases with PCOS. METHODS: Among 40 patients
      diagnosed with PCOS, one study arm was administered EE/CA (n=20, cyproterone
      acetate 2 mg, ethinylestradiol 35 microg) and the other was administered
      metformin (1,700 mg) combined with EE/CA (n=20, cyproterone acetate 2 mg,
      ethinylestradiol 35 microg). Soluble intercellular adhesion molecule-1 (sICAM-1),
      soluble endothelial leukocyte adhesion molecule-1 (sE-selectin), soluble vascular
      cell adhesion molecule-1 (sVCAM-1), soluble leukocyte endothelial cell adhesion
      molecule-3 (sP-selectin), lipid profile, androgens, insulin, and HOMA-IR values
      were assessed prior to treatment and after 3 months of therapy. RESULTS: The
      comparison of the groups receiving EE/CA and EE/CA+metformin revealed a
      significant reduction in sVCAM (1,445+/-614 vs 1,167+/-482, p<0.05) and sICAM
      (442+/-141 vs 345+/-118, p<0.05) values relative to pre-treatment values while no
      significant changes were detected in sE-selectin and sP-selectin levels relative
      to pre-treatment levels in the EE/CA+metformin group (p>0.05). In the post
      treatment period, sVCAM, sICAM, sE-selectin values did not significantly change
      compared to the pre-treatment values in EE/CA group (p>0.05). sP-selectin levels
      were also decreased but missed the significance in EE/CA group (229.4+/-68.0 vs
      189.6+/-65.0, p=0.08). CONCLUSION: These results demonstrate that EE/CA+metformin
      treatment reduced inflammation markers in cases with PCOS compared to EE/CA
      treatment. The clinical relevance of this conclusion may be clarified by longer
      metformin treatment and clinical follow-up.

PMID- 19602787
TI  - Low vital capacity is associated with diabetes despite inverse relationships with
      metabolic risk factors in lean Japanese men.
AB  - BACKGROUND: There is no study examining the relationships between vital capacity
      and diabetes or metabolic risk factors in lean subjects. METHODS: Cross-sectional
      relationships between % vital capacity (%VC) and diabetes and metabolic risk
      factors were examined in Japanese subjects using medical check-up data from 2,079
      men and 1,215 women. Subjects were divided into lean (BMI <23 kg/m(2)) and obese
      (BMI >or=23 kg/m(2)) groups and then subdivided into lower %VC (<or=95%) and
      higher %VC (>or=96%) subgroups by gender. Metabolic risk factors and prevalence
      of diabetes and MS were compared between the subjects in each group, and then
      excluding current smokers and between subjects with the lowest quartile of %VC
      and those with the highest quartile of %VC in the lean men group. Spearman's
      correlation coefficients between %VC and metabolic risk factors were calculated
      separately in obese subjects and in lean subjects by gender. RESULTS: The
      prevalence of diabetes, but not metabolic syndrome, was significantly higher in
      subjects with the lower %VC than in those with the higher %VC in the lean men
      despite the fact that age, obesity parameters, systolic and diastolic blood
      pressures were significantly lower in subjects with the lower %VC than in those
      with the higher %VC and triglycerides, high-density lipoprotein cholesterol, high
      sensitivity C-reactive protein, white blood cell count, and heart rate were not
      significantly different between the two groups. CONCLUSION: Low vital capacity
      was significantly associated with diabetes in lean Japanese men despite inverse
      relationships with metabolic risk factors.

PMID- 19602788
TI  - Inflammatory cells in lung disease associated with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with numerous pulmonary
      manifestations. However, the inflammatory mechanism remains undetermined. We
      studied the features of inflammatory cells in bronchoalveolar lavage (BAL) fluid
      and biopsy lung tissue from patients with RA-associated lung disease. METHODS:
      BAL findings were statistically compared between diseases. We divided RA patients
      into two groups, airway lesion group (AW) and interstitial lesion group (INT)
      according to predominant HRCT findings and compared the BAL findings. We
      immunohistochemically stained lung tissue for CD4, CD8, CD20, and CD163 and
      counted the immunopositive cells in five different regions. PATIENTS: Twenty
      patients fulfilling the Japanese criteria for RA, 13 patients with systemic
      sclerosis (SSc), and 21 patients with polymyositis and dermatomyositis (PM-DM)
      with pulmonary disease detected by high-resolution CT (HRCT) were enrolled in
      this study. RESULTS: As for BAL in RA, we found a lower lymphocyte frequency with
      higher CD4/8 ratio compared with PM-DM and a higher neutrophil percentage than
      both PM-DM and SSc. Nine and eleven patients with RA were classified into AW and
      INT groups, respectively. BAL findings did not differ between the two groups.
      Immunohistochemically, most CD4(+) and CD20(+) lymphocytes were accumulated in
      lymphoid follicles and in the alveolar wall and T-lymphocytes; in particular
      CD8(+) lymphocytes were predominant in lung interstitium. CONCLUSION: These
      results suggest that 1) neutrophils may play an important role, 2) the
      inflammatory mechanism may be similar between airway lesion and interstitial
      pneumonia, and 3) CD8(+) lymphocytes may be major inflammatory cells in lung
      interstitium in RA-associated interstitial lung disease.

PMID- 19602789
TI  - Donepezil-induced adverse side effects of cardiac rhythm: 2 cases report of
      atrioventricular block and Torsade de Pointes.
AB  - Acetylcholinesterase inhibitors (AChIs) are widely used in the treatment of mild
      to-moderate Alzheimer's disease (AD), but their cholinergic effects could
      generate adverse side effects in the cardiovascular system. This report presents
      the cases of 2 patients who experienced adverse side effects of cardiac rhythm
      with QT prolongation caused by Donepezil. Both of them improved to the original
      rhythm and shortened QT intervals after the discontinuation of Donepezil. The
      present cases suggest that the cholinergic effects of Donepezil could induce
      adverse side effects on cardiac rhythm and careful consideration is needed for
      the patients treated by Donepezil.

PMID- 19602790
TI  - Neuroaspergillosis in an immunocompetent patient successfully treated with
      voriconazole and a corticosteroid.
AB  - Aspergillosis of the central nervous system (CNS) is an uncommon infection,
      mainly occurring in immunocompromised patients. We report a case of nasocerebral
      aspergillosis in an immunocompetent patient successfully treated with
      voriconazole and a corticosteroid. Magnetic resonance imaging (MRI) showed
      contrast enhancement surrounding the brainstem and cerebellum with intramedullary
      pontine and cerebellar T2-hyperintense lesions. The patient's symptoms and MRI
      abnormalities improved after voriconazole and corticosteroid treatment; however,
      discontinuation of the corticosteroid caused a worsening of the T2-hyperintense
      lesions, whereas resuming it resulted in its improvement. This suggested that
      these T2-hyperintense lesions may be due to secondary inflammation caused by
      aspergillosis and not the aspergillosis itself. We conclude that treatment with a
      combination of voriconazole and a corticosteroid appears to be effective for the
      treatment of some patients with CNS aspergillosis.

PMID- 19602791
TI  - Pulmonary thrombosis with transient antiphospholipid syndrome after mononucleosis
      like illness.
AB  - Antiphospholipid antibodies (aPL) have been reported to occur in numerous viral
      infections. We report a 24-year-old Japanese woman, who developed multiple venous
      thrombosis associated with the elevation of anticardiolipin IgM after acute viral
      infection presenting a mononucleosis-like illness. Two months later, aPL and
      thromboses disappeared. In this case both parvovirus B19 and cytomegalovirus
      antibodies IgM were elevated, which indicated the possibility of cross-reaction.

PMID- 19602792
TI  - Acute myocardial infarction with myocardial perfusion defect detected by contrast
      enhanced computed tomography.
AB  - The first case was a 68-year-old woman who had acute migratory pain from back to
      anterior chest and the second case was 66-year-old man with a cardiac tamponade.
      Two cases were demonstrated with a low density area of the left ventricular
      postero-lateral wall with conventional contrast-enhanced computed tomography (CE
      CT) performed to differentiate the diagnosis of acute coronary syndrome and acute
      aortic dissection. Subsequent coronary angiograms showed the lesions of left
      circumflex. These cases of early contrast-defect corresponded to a decreased
      myocardial blood flow with AMI. CE-CT image facilitated the diagnosis of AMI
      preceding CAG examination.

PMID- 19602793
TI  - Multiple myeloma with a variant Burkitt-type translocation, t(2;8)(p12;q24),
      associated with hyperammonemia.
AB  - We report an 82-year-old Japanese woman with multiple myeloma (MM). She developed
      disorientation due to hyperammonemia after melphalan and prednisolone therapy and
      abruptly died with a rapid clinical course. Karyotypic analysis of bone marrow
      showed complex abnormalities including a variant Burkitt-type translocation,
      t(2;8)(p12;q24), but the patient had IgG-lambda type M-proteinemia. Although
      patients with MM associated with hyperammonemia have been sporadically reported
      and their prognosis is poor, specific chromosomal abnormalities in the lesion
      have not been well characterized. It is, therefore, important to accumulate such
      patients to find a possible relationship between hyperammonemia and chromosomal
      abnormalities.

PMID- 19602794
TI  - Thyrotoxicosis complicated with dysphagia.
AB  - A 36-year-old man was admitted to our hospital because of general fatigue and
      dysphagia. He had experienced progression of thyrotoxic symptoms of weight loss,
      palpitation and sweating for several months. On admission, he showed thyroid
      storm associated with dysphagia and aspiration pneumonia. Dysphagia was restored
      completely with 2 months after intensive treatment with anti-thyroid agent, beta
      blocker, potassium iodide and glucocorticoid for thyroid storm. Although
      dysphagia is an uncommon manifestation, we should keep in mind that dysphagia may
      be one of symptoms of thyrotoxic myopathy.

PMID- 19602795
TI  - Cerebral hemorrhage, splenic and renal embolisms due to infective endocarditis.
AB  - Infective endocarditis is occurring more and more frequently in elderly persons
      and it has been associated with various clinical, bacteriological, and prognostic
      features. We present a 63-year-old woman with infective endocarditis which is the
      first reported case with cerebral hemorrhage, splenic and renal embolisms.

PMID- 19602798
TI  - [Reproducibility of dynamic chest radiography with a flat-panel detector -
      respiratory changes in pixel value].
AB  - Dynamic chest radiography using a flat panel detector (FPD) with a large field of
      view is expected to be a useful pulmonary functional evaluation method based on
      the respiratory changes in pixel value. For clinical use as a follow-up and
      therapeutic evaluation tool, the system must have a high degree of
      reproducibility in measurements of pixel values. The present study was performed
      to investigate the reproducibility of respiratory changes in pixel values.
      Dynamic chest radiographs of five normal subjects and one patient were obtained.
      Imaging was performed twice in each subject. The slope (X-ray translucency
      variation) was then calculated from the changes in pixel value from distance lung
      apex-diaphragm, and the slopes of two sequences were compared. The results showed
      there were no significant differences in changes in pixel value between the two
      sequences in all normal subject (5 males, p>0.05). The results indicated that the
      present method has reproducibility for measuring pulmonary function and also has
      potential as a tool for follow-up and therapeutic evaluation.

PMID- 19602797
TI  - [Pulmonary functional diagnostic imaging using a dynamic flat-panel detector:
      comparison with findings in pulmonary scintigraphy].
AB  - Pulmonary ventilation and circulation dynamics are reflected on dynamic chest
      radiographs as changes in X-ray translucency,i.e., pixel values. The present
      study was performed to develop a pulmonary functional evaluation method based on
      the changes in pixel value, and to investigate the clinical usefulness of our
      method. Sequential chest radiographs of 20 subjects (abnormal,n=12; normal,n=8)
      during respiration were obtained with a dynamic flat-panel detector (FPD) system.
      The average pixel value in each local area was measured tracking the same area.
      To facilitate visual evaluation, the results were mapped on the original image
      using a grayscale in which small changes were shown in black and large changes
      were shown in white. In our clinical evaluation in comparison with a pulmonary
      scintigraphy, pulmonary ventilation disorder was indicated as a reduction of
      changes in pixel values. In many patients, there was a correlation between our
      result and a pulmonary scintigraphy (0.7<r, 4 cases; 0.4<r<or=0.7, 6 cases;
      0.2<r<or=0.4, 1 case; 0<r<or=0.2, 1 case). The present method with real-time
      computer analysis is expected to be a rapid and simple method for evaluating
      pulmonary function and as an additional examination in conventional chest
      radiography.

PMID- 19602799
TI  - [Comparative evaluation of 3D images reconstructed of MDCT or cone-beam CT: with
      special attention to depiction with abdominal IVR].
AB  - Diagnosis by CTHA (CT during hepatic arteriography) and CTAP (CT during arterio
      portography) is indispensable in the treatment of hepatocellular carcinoma (HCC).
      An IVR-CT system makes it possible to perform accurate diagnosis and treatment of
      HCC in a short period of time. In recent years, attention has been drawn to cone
      beam CT (CBCT) using a flat panel detector (FPD) angio-system, and the
      application of CBCT for CTAP and CTHA has been reported. However, it is well
      known that CBCT easily generates artifacts on the images, so it is necessary to
      use CBCT according to the intended purpose. The purpose of this study was to
      evaluate 3-D images reconstructed by MDCT or CBCT, image noise, and low-contrast
      resolution in a phantom with a tumor mimic model. From our results, CBCT images
      showed distortion and blurring, and it was difficult to visualize a tumor model
      of 7 mm or less. In addition CBCT can create only a small area of 3-D vascular
      mapping. In conclusion, it is considered that CBCT cannot be used in place of
      conventional CTHA or CTA for the treatment of HCC.

PMID- 19602800
TI  - [A characteristic of angiographic cone-beam CT].
AB  - Angiographic cone-beam CT, called DynaCT by SIEMENS, is a 3D imaging tool
      reconstructed from projection data by a rotational C-arm with a flat panel
      detector. It can visualize low-contrast objects such as soft tissue or small
      vessels as well as high-contrast structures such as enhanced vessels or bone. We
      need to understand its image characteristics and dose distribution during 200
      degree rotation around a patient. In this research, we evaluated fundamental
      characteristics and dose effectiveness for optimized clinical images. DynaCT,
      including soft tissue information and isochronal voxel data along the z-axis,
      could provide enough CT-like image quality for IVR use. In addition, evaluation
      of accumulated dose distribution helped us to predict and avoid the occurrence of
      radiodermatitis. Thus, DynaCT is useful as a support and navigation tool for IVR.

PMID- 19602801
TI  - [Combinations of scan parameters and image quality at C-arm CT for abdominal
      imaging].
AB  - We measured the contrast-to-noise ratio (CNR) and evaluated low-contrast images
      and streak artifacts to optimize abdominal C-arm CT imaging, and we investigated
      the view number, acquisition matrix, and pixel depth. To measure CNR, we filled
      0.125-1.0-inch cavities in an American Association of Physicists in Medicine
      (AAPM) CT performance phantom with a sodium chloride solution. Five radiological
      technologists visually evaluated the noise, signal conspicuity at low-and high
      signal density, and the overall image quality using paired comparisons based on
      Thurstone's law. In a given acquisition matrix, the total view number had the
      greatest effect on the image noise, artifacts, and signal detectability on C-arm
      CT images. For a given incident dose per view on the flat-panel detector (FPD),
      fewer images with noise and streak artifacts resulted when a larger view number
      was selected.

PMID- 19602802
TI  - [Optimization of histogram analysis for pediatric digital chest radiography using
      flat panel detector system].
AB  - Optical density of the lung area in pediatric digital chest radiography using an
      indirect flat panel detector (FPD) system were changed enormously by the
      influence of such factors as the size of lung area, gas of retroperitoneum, and
      so on. Our purpose in this study was to improve the stability of lung density on
      output images by means of optimizing histogram analysis. Chest images of a lung
      phantom were taken at various X-ray tube voltages and processed using a half-type
      region of interest (ROI) for the lung area. The shape of the histogram obtained
      by two different calculation methods including frequency distribution and
      cumulative relative frequency were compared, and digital chest images of 110
      clinical cases in our hospital were classified into three age-groups (under 6
      years old, over 6 years old and under 13 years old, and over 13 years old) and
      their histograms were analyzed. In conclusion, it was important that to analyze
      the histograms of age-groups, a cumulative relative frequency histogram should be
      used because the influence of X-ray tube voltage was lower than the frequency
      distribution histogram, and stabilized lung density under 6 years old could be
      obtained if the value of the imaging parameter for lung density from default was
      90% to 85% or 80% because the distribution of lung area and its center value were
      significantly lower than in those over 13 years old.

PMID- 19602803
TI  - [Measurement of residual effect in the amorphous selenium flat panel detector
      system].
AB  - The purpose of this study was to evaluate the residual effect generated by the
      amorphous selenium flat panel detector system (a-Se FPD). A residual effect
      occurs as a result of the addition of delayed electrons by previous X-ray
      irradiation joining the signal and change in detector sensitivity caused by hole
      electron recombination or trapped electrons in a-Se. To evaluate the effect of
      previous radiation exposure, we irradiated a-Se FPD that were half-shielded by a
      3 mm thick lead plate. A residual effect was generated in irradiated areas, with
      the unirradiated areas serving as reference points. Next, we removed the lead
      plate and took a new image using uniform irradiation. The difference in pixel
      value between irradiated and nonirradiated areas was measured using a variety of
      time intervals between each exposure. Through a comparison of pixel values from
      images taken over various time intervals, we discovered our system needs 20 hours
      to return to a normal state and become capable of producing a residual-free
      image.

PMID- 19602804
TI  - [Evaluation of FOV size on cerebral three-dimensional rotational digital
      subtraction angiography with flat panel detector system].
AB  - In interventional neuroradiology, three-dimensional rotational digital
      subtraction angiography (3D-DSA) is very useful for the spatial grasp of the
      location and size of an intracranial cerebral aneurysm. The purposes of this
      study were to evaluate the property of three-dimensional image dependence on the
      respective field of view (FOV) size in a flat-panel detector (FPD) using vessel
      phantoms, and to optimize clinically. The indices of three-dimensional image
      properties such as profile curve (FWHM, FWTM), digital value, and image noise
      were evaluated using a vessel phantom with a different diameter. As a result, in
      the case of a 6-inch FOV size of the FPD, the relative diametral rate of change
      from the actual value of the vessel phantom was least for all FOV sizes. This
      study demonstrated that the difference in FOV size in 3D-DSA affects the three
      dimensional object's reproducibility. Furthermore, as for this 3D-DAS system,
      three-dimension images such as a VR image might be processed more faithfully,
      since an FOV size of 6 inches has the highest reproducibility of objects.

PMID- 19602805
TI  - [Angiography: clinical evaluation and physical characteristics of FPD - the
      clinical impact caused by detector characteristics].
AB  - We have been engaged in clinical work using DSA, the first in the world, under a
      joint study agreement with Hitachi Medical Corporation on the use of the Flat
      Panel Detector (FPD) since 2001. We are now in the stage where a certain
      evaluation process has been finished, but the FPD performance study in
      angiography has just begun, and, therefore, its clinical evaluation results are
      very few. Therefore, we studied the relativity between clinical images and
      physical characteristics in order to examine the characteristics of FPD by
      referencing them to clinical images. We did an evaluation of the clinical images
      to which their physical characteristics such as granularity, resolution,
      contrast, etc., are reflected by comparing FPD and I.I. images.

PMID- 19602806
TI  - [A useful technique for various examinations applied to the novel multi-purpose
      R&F table systems with flat panel detector].

PMID- 19602807
TI  - [New technology of Toshiba X-ray angiography system].

PMID- 19602808
TI  - [Development and applications of interventional 3D imaging system based on FPD].

PMID- 19602809
TI  - [Development of clinical application technique of high speed continuous
      acquisition FPD system].

PMID- 19602810
TI  - [The latest technologies and information on GE Innova(IQ) in 2009].

PMID- 19602811
TI  - [The latest technology of Allura Xper FD20 series].

PMID- 19602812
TI  - [High precision radiotherapy using flat panel detectors].

PMID- 19602813
TI  - [Clinical implementation of 4 MV X-ray cone beam CT from a graphite target].

PMID- 19602814
TI  - [A role of FPD in radiation therapy - on board imager].

PMID- 19602815
TI  - [Expectation of new diagnostic imaging with a dynamic flat-panel detector (FPD)].

PMID- 19602816
TI  - [Basic lecture - physical image quality assessment in digital radiography].

PMID- 19602817
TI  - [Measurement manual of magnetic field leakage for MR facilities - part 2].

PMID- 19602818
TI  - A novel device, the anglerfish countertractor, is easy and safe to use in
      patients undergoing endoscopic submucosal dissection of gastric mucosal cancer.

PMID- 19602819
TI  - Long-term prognosis of patients with Kawasaki disease: at risk for future
      atherosclerosis?
AB  - Kawasaki disease causes coronary artery lesions, such as dilatation, aneurysms,
      stenosis, and even occlusion in young children, and is one of the most common
      acquired heart diseases in developed countries. More than 10,000 new cases are
      reported in Japan every year. In its acute phase, severe coronary arteritis
      induces morphological changes in coronary arteries. Treatments for Kawasaki
      disease aim to eliminate coronary artery inflammation as quickly as possible to
      reduce the chance of causing coronary lesions. Immunoglobulin therapy with
      aspirin has become the standard therapy of first choice and helps attenuate
      coronary lesions. In addition to coronary artery disturbances in the acute phase,
      sclerotic vascular changes were observed in post-Kawasaki disease patients who
      did not have coronary lesions in the acute phase. Recent studies have revealed
      peripheral vasculature endothelial dysfunction in post-Kawasaki disease patients
      with and without coronary lesions. The risk factors for the development of
      atherosclerosis in adults, such as C-reactive protein, oxidative stress, and
      inflammatory cytokines, are also increased in the remote phase of Kawasaki
      disease. This morphological and functional endothelial dysfunction as Kawasaki
      disease vascular sequelae may suggest the early development of atherosclerosis in
      patients with Kawasaki disease. However, no direct evidence for this early
      development has been found so far. Kawasaki disease was first reported slightly
      more than 40 years ago. The first documented post-Kawasaki disease patients are
      now becoming old enough to have atherosclerosis. Some case reports suggest
      myocardial infarction with atherosclerotic changes in young adults who are
      believed to have a history of Kawasaki disease. This paper reviews Kawasaki
      disease from the perspective of long-term prognosis.

PMID- 19602820
TI  - Leukemogenesis of b2a2-type p210 BCR/ABL in a bone marrow transplantation mouse
      model using a lentiviral vector.
AB  - The BCR/ABL fusion oncogene found in Philadelphia-positive leukemia exists in
      three principle forms: p190, p210 and p230. P210 BCR/ABL is commonly found in
      patients with chronic myelogenous leukemia (CML) and is further categorized into
      b3a2 or b2a2 subtypes on the basis of the BCR breakpoint. Although these 2
      subtypes may be clinically heterogeneous, only the b3a2 BCR/ABL gene has been
      extensively studied at the molecular and cellular levels. In the present study,
      we compared the in vivo leukemogenic activity of the b3a2 and b2a2 BCR/ABL genes
      by using lentiviral transduction/transplantation mouse models. Lineage-depleted
      bone marrow cells of BALB/c mice were transduced with a lentiviral vector
      including either b2a2 or b3a2 BCR/ABL cDNA and then transplanted into lethally
      irradiated mice. In this model, p210 BCR/ABL subtype developed only B220(+),
      CD3e(-), Gr1(-), and Mac1(-) B-cell acute lymphoblastic leukemia but not myeloid
      leukemia. There were no differences in the incidence of leukemogenesis, the white
      blood cell count, the percentage of blast cells, or the survival rates between
      the b2a2 and b3a2 groups. We have demonstrated that b2a2-type BCR/ABL has
      leukemogenic activity similar to that of b3a2-type BCR/ABL.

PMID- 19602821
TI  - The effect of doxazosin mesilate on cerebral blood flow in patients with
      hypertension and chronic cerebral infarction.
AB  - alpha(1)-Adrenoceptor antagonists are useful antihypertensive agents for patients
      with hypertension who have hyperlipidemia, benign prostatic hyperplasia, or
      pheochromocytoma. The purpose of this study was to evaluate the effect of the
      alpha(1)-adrenoceptor antagonist, doxazosin mesilate, on cerebral blood flow
      (CBF) and flow velocity in the common carotid artery in patients with
      hypertension and chronic cerebral infarction. Doxazosin mesilate (1 mg/day) was
      orally administered for 4 to 8 weeks to 7 patients with hypertension 4 weeks
      after the onset of cerebral infarction. We determined blood pressure, heart rate,
      CBF measured with autoradiography single photon emission computed tomography
      (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine ((123)I-IMP) as a tracer, and
      the maximum, minimum and mean flow velocities in the common carotid arteries
      measured with duplex carotid ultrasonography before and 4 to 8 weeks after the
      beginning of treatment. Mean CBF was defined as the mean count of tracer from the
      8 regions of interest (ROIs) in the frontal, parietal, occipital, and temporal
      cortices of the cerebral hemisphere. Values were analyzed with paired t tests.
      With administration of doxazosin mesilate, systolic pressure significantly
      decreased from 152 +/- 11 to 137 +/- 7 mmHg (p<0.01), but diastolic pressure and
      heart rate were unchanged. Mean CBF was improved significantly from 32.0 +/- 4.1
      to 34.7 +/- 4.1 mL/100 g brain/min (p<0.01) in the ipsilateral cerebral cortex
      and from 32.6 +/- 6.2 to 36.2 +/- 5.1 mL/100 g brain/min (p<0.05) in the
      contralateral cerebral cortex. The maximum, minimum, and mean flow velocities in
      the bilateral common carotid arteries were not changed significantly. In the
      present study, the improvement of mean CBF in the ipsilateral and contralateral
      cerebral cortices was demonstrated in patients with hypertension and chronic
      cerebral infarction after the treatment with doxazosin mesilate. Doxazosin
      mesilate might be an effective antihypertensive agent for hypertensive chronic
      cerebral infarction.

PMID- 19602822
TI  - Inflammatory pseudotumor in the liver associated with intrahepatic bile duct
      stones mimicking malignancy.
AB  - We describe a 71-year-old man with an inflammatory tumor arising in segment 5 of
      the liver. The patient was admitted because of acute pain in the right upper
      quadrant of the abdomen and fever. Initial laboratory tests revealed the
      following: serum alkaline phosphatase concentration, 634 IU/L; serum gamma
      glutamic transpeptidase concentration, 1,378 IU/L; serum C-reactive protein
      concentration, 0.89 mg/dL; and total bilirubin concentration, 8.9 mg/dL.
      Abdominal ultrasonography, computed tomography (CT), and magnetic resonance
      imaging showed a mass, 3 cm in diameter, in segment 5 of the liver. Magnetic
      resonance cholangiopancreatography showed a lesion of moderate-to-high signal
      intensity on T2-weighted images of segment 5. Endoscopic retrograde
      cholangiopancreatography revealed a common bile duct stone. The intrahepatic bile
      ducts of segment 5 could not be visualized after the use of contrast material.
      Endoscopic sphincterotomy was performed to remove the common bile duct stone.
      Antibiotics were administered soon after stone removal, and fever gradually
      resolved. Positron emission tomography revealed hot spots in segment 5 of the
      liver. Three weeks after discharge, the patient was readmitted with an acute pain
      in the right upper quadrant of the abdomen. Abdominal ultrasonography, CT, and
      magnetic resonance imaging showed enlargement of this area. Inflammatory changes
      of segment 5 due to cholangitis with intrahepatic bile duct stones was diagnosed.
      Because malignant disease could not be completely ruled out, segment 5 of the
      liver was resected. Macroscopic examination of the resected specimen revealed a
      gray, fibrotic, solid tumor associated with intrahepatic bile duct stones.
      Microscopic examination of the tumor showed proliferation of spindle-shaped
      myofibroblastic cells in a mixed myxoedematous, dense fibrotic stroma, associated
      with infiltration by various acute and chronic inflammatory cells. The
      postoperative course was uneventful, and the patient was discharged on
      postoperative day 16.

PMID- 19602823
TI  - Infected hepatic cyst treated with percutaneous transhepatic drainage.
AB  - Simple hepatic cysts are common benign lesions that are usually asymptomatic and
      require no treatment. However, complications can occur. This report describes a
      patient with an infected hepatic cyst treated with percutaneous transhepatic
      drainage. A 64-year-old woman presented at a nearby hospital because of acute
      right-upper-quadrant pain, mild left-lower-quadrant pain, diarrhea, and fever.
      She was admitted and received intravenous antibiotics for 1 week, but symptoms
      persisted. She was, therefore, referred to our hospital. On admission,
      ultrasonography demonstrated multiple hepatic cysts. One 13-cm lesion was
      hypoechoic, unlike the other simple cysts, which were anechoic. Computed
      tomography showed that the density of the hypoechoic cyst was slightly higher
      than that of the other cysts. The wall of the cyst was thickened and showed
      contrast enhancement. On initial laboratory tests the serum C-reactive protein
      concentration was 18.49 mg/dL, and the white-cell count was 13,300/microL. An
      infected hepatic cyst was suspected, and percutaneous transhepatic drainage of
      the cyst was performed. A catheter was inserted into the cyst, and dark red fluid
      was obtained. The right-upper-quadrant pain gradually resolved after drainage. An
      infected hepatic cyst was diagnosed, and system antibiotics were administered.
      However, the mild left-lower-quadrant pain persisted. No pathogens were isolated
      from the drainage fluid. Minocycline hydrochloride (200 mg) was injected, and the
      catheter was clamped for 30 minutes, once daily for 3 days. The serum C-reactive
      protein concentration was 1.78 mg/dL, and the white-cell count was 5,700/microL.
      The left-lower-quadrant pain resolved, and colonoscopic examination revealed
      multiple diverticula of the sigmoid colon. Infection has not recurred, and the
      hepatic cyst has not become larger.

PMID- 19602824
TI  - Varicella-associated purpura fulminans and multiple deep vein thromboses: a case
      report.
AB  - Varicella-associated purpura fulminans is a rare syndrome associated with
      substantial morbidity and mortality. General supportive care, heparinization, and
      plasma infusions are the mainstays of treatment. A patient aged 8 years and 8
      months with purpura fulminans and multiple deep vein thromboses after varicella
      infection because of deficiencies of proteins C and S is presented in this case
      report.

PMID- 19602825
TI  - Follicular carcinoma arising from the pyramidal lobe of the thyroid.
AB  - We present a rare case of follicular carcinoma arising from the pyramidal lobe of
      the thyroid in a 21-year-old woman. Radical resection of the thyroid isthmus was
      performed, followed by adjuvant hormonal therapy with levothyroxine. After 15
      months of follow-up, the patient remains disease-free. Thyroid carcinoma in
      children and adolescents is rare, and also rarely arises in the pyramidal lobe.
      To our knowledge, this is the first report of this type of neoplasm arising from
      the thyroid pyramidal lobe. We are following up this case carefully, and if
      recurrence or metastasis or both occur, we plan to perform total thyroidectomy
      and ablation with (131)I. This case suggests the importance of the differential
      diagnosis of midline cervical masses and the management of this type of neoplasm
      in adolescents.

PMID- 19602826
TI  - Balloon-occluded retrograde transvenous obliteration for gastric varices in a
      child with extrahepatic portal venous obstruction.
AB  - Balloon-occluded retrograde transvenous obliteration (B-RTO) has been used
      successfully to treat gastric varices in adults. However, only a few case reports
      of B-RTO in children have been published. We describe a child who had gastric
      varices with extrahepatic portal venous obstruction (EHO). A 12-year-old boy
      presented to the pediatric clinic with anemia and tarry stools. He was referred
      to our department to receive additional treatment for gastric varices. Endoscopy
      revealed spurting bleeding from gastric varices, and emergent endoscopic
      injection sclerotherapy was performed. Angiography showed cavernous
      transformation of the portal vein, hepatofugal flow of the left gastric vein,
      gastric varices, and gastrorenal shunt. The gastric varices were not eradicated
      adequately with endoscopic sclerotherapy because of excessive regurgitant blood
      flow against the portal venous pressure. B-RTO combined with partial splenic
      embolization (PSE) was therefore performed. The gastric varices were completely
      eradicated with no complications. This is, to our knowledge, the first report
      describing the use of B-RTO combined with PSE in a child with EHO who had gastric
      fundal varices. B-RTO combined with PSE is not excessively invasive and is
      effective and safe for children. This procedure is therefore recommended for the
      treatment of gastric varices in children.

PMID- 19602827
TI  - Is glycemic index of food a feasible predictor of appetite, hunger, and satiety?
AB  - This review assesses the feasibility of using glycemic index (GI) as a predictor
      of appetite, hunger and satiety by surveying published human intervention
      studies. We also discuss the relationship between GI and two appetite/satiety
      control hormones, leptin and ghrelin. Ingestion of high-GI food increased hunger
      and lowered satiety in short-term human intervention studies. This effect may be
      attributed to the rapid decline in blood glucose level following a
      hyperinsulinemic response caused by a sharp and transient increase in blood
      glucose level that occurs after the ingestion of high-GI food, which is defined
      as the glucostatic theory. However, appetite, hunger and satiety after the
      ingestion of foods with varying GI were inconsistent among long-term human
      intervention studies. From the few relevant long-term studies available, we
      selected two recent well-designed examples for analysis, but they failed to
      elicit clear differences in glycemic and insulinemic responses between high- and
      low-GI meals (consisting of a combination of different foods or key carbohydrate
      rich foods incorporated into habitual diets). One of the reasons that these
      studies could not predict glycemic response to mixed meals is presumably that the
      GI of each particular food was not reflected in that of the mixed meals as a
      whole. Thus, it is difficult to conclude that the GI values of foods or mixed
      meals are a valid long-term predictor for appetite, hunger and satiety. Both
      insulin and insulin-mediated glucose uptake and metabolism in adipose tissue
      affect blood leptin concentration and its diurnal pattern. Circulating ghrelin
      level is suppressed by carbohydrate-rich meals, presumably via glycemia and
      insulinemia. Accordingly, low-GI foods may not necessarily increase satiety or
      suppress appetite and/or hunger because of the lack of insulin-mediated leptin
      stimulation and ghrelin suppression. However, insulin-mediated leptin stimulation
      and ghrelin suppression per se is not consistent among studies; thus we were not
      able to identify a clear relationship among GI, satietogenic leptin, and
      appetitic ghrelin.

PMID- 19602828
TI  - Marginal vitamin A deficiency affects lung maturation in rats from prenatal to
      adult stage.
AB  - Mild or marginal vitamin A deficiency (MVAD) is still a serious and widespread
      public health problem in pregnant women and children in developing countries.
      This study investigated rat lung maturation from prenatal to adult stage during
      pregnancy and postnatal MVAD and the recovery after postnatal vitamin A
      supplementation (VAS). Adult female rats and their offspring were randomized into
      three groups. 1. CONTROL: the mothers and offspring received a normal diet.2.
      MVAD: The mothers and offspring received a MVAD diet.3. VAS: the mothers received
      MVAD diet till parturition, and then received the normal diet. The offspring of
      the VAS group were given low-dose vitamin A from postnatal day 1 to day 7 and
      received the normal diet after weaning. The lung development, structure, and
      collagen and elastic fiber of offspring were monitored by morphometric analysis
      at age 1 d, 2 and 8 wk, respectively. Lower body weight, lung weight, reduced
      numbers of alveoli and total alveolar surface area as well as increased alveoli
      septa thickness was observed in MVAD compared to that in the control animals.
      Increased collagen deposits and decreasing elastic fiber were found in MVAD rats.
      However, all of these were significantly improved in VAS-treated animals. These
      data suggest that the rat lung is sensitive to MVAD during the developing stage.
      Early postnatal vitamin A supplementation can partially restore the normal lung
      structure.

PMID- 19602829
TI  - 1Alpha,25 dihydroxyvitamin D3: therapeutic and preventive effects against
      oxidative stress, hepatic, pancreatic and renal injury in alloxan-induced
      diabetes in rats.
AB  - Diabetes mellitus is a major endocrine disorder and a growing health problem in
      most countries which can be ameliorated by numerous bio-molecules such as
      1alpha,25 dihydroxyvitamin D3 [1alpha,25(OH)2VD3]. With this in mind, the current
      study investigated the therapeutic and preventive effects of 1alpha,25(OH)2VD3 on
      diabetes and its side effects: toxicity in liver, pancreas and kidneys. Our
      results show that administration of 1alpha,25(OH)2VD3 in diabetic rats increased
      the plasmatic insulin level, favored the normal blood glucose levels and
      normalized the hepatic glycogen concentration. In addition, 1alpha,25(OH)2VD3
      enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GPX) (by 207, 52 and 72%, respectively) compared to diabetic rats. It also
      reduced lipid peroxidation and the indices of toxicity in liver and kidneys by
      significantly decreasing alkaline phosphatases (PAL), aspartate and lactate
      transaminase (AST and ALT) activities, total and direct bilirubin, triglycerides
      (TG), cholesterol, creatinine, urea and iron levels in diabetic rats. Moreover,
      the plasmatic non-enzymatic antioxidant level of HDL-cholesterol, magnesium (Mg),
      calcium (Ca) and copper (Cu) increased after 1alpha,25(OH)2VD3 administration.
      The administration of 1alpha,25(OH)2VD3 in diabetic rats protects against alloxan
      induced histological changes in pancreas. CONCLUSION: from these data, it is
      concluded that 1alpha,25(OH)2VD3 might be useful for the therapy and prevention
      of diabetes and the numerous side effects especially toxicity in liver, pancreas
      and kidneys and this protective effect is more obvious in our preventive
      experiment.

PMID- 19602830
TI  - Protective effect of grape seed proanthocyanidins extracts on reperfusion
      arrhythmia in rabbits.
AB  - Reperfusion arrhythmia (RA) is one of the main complications which are also an
      important cause of sudden cardiac death. The aim of this study was to clarify
      whether grape seed proanthocyanidins extracts (GSPE) were therapeutic agents
      against RA. The models of cardiac ischemic reperfusion injury were established in
      rabbits. GSPE (100 mg/kg, and 250 mg/kg body weight/d, respectively) were
      administered for 3 wk. The incidence rates of arrhythmias before and after
      reperfusion of each group were recorded, cardiac infarction area and
      microstructures of cardiac cells of each rabbit were observed, and the expression
      of connexin 43 (Cx43) was detected by immunohistochemistry. Data were analyzed
      using the Leica Qwin V3 image analysis system. Reperfusion induced arrhythmia.
      Ventricular fibrillation (VF) occurred during the early phase of reperfusion
      after ischemia. Our results showed that GSPE treatment significantly reduced the
      incidence of VF and the infarction size compared with the model control group.
      Moreover, the intercalated disks in the model control group showed collapse,
      displacement and even the formation of cisterns. After being treated by GSPE, the
      intercalated disks were improved and there were less collapse and displacement.
      The expression of Cx43 was improved by GSPE treatment, and high dose of GSPE
      resulted in significant improvement. The study suggests that GSPE has a
      protective effect on myocardial ischemic reperfusion arrhythmias, which may be
      mediated by inhibiting the degradation of Cx43 and enhancing gap junctional
      conductance.

PMID- 19602831
TI  - Carotenoid, tocopherol, and fatty acid biomarkers and dietary intake estimated by
      using a brief self-administered diet history questionnaire for older Japanese
      children and adolescents.
AB  - We investigated the association between nutrient biomarkers and dietary intake
      estimated using a brief self-administered dietary history questionnaire (BDHQ)
      for Japanese children and adolescents. Blood samples were collected from 398
      subjects (5th graders of elementary school aged 10-11 y, and 2nd graders of
      secondary schools aged 13-14 y) randomly selected from among students in Shunan
      City, Japan, who were then required to answer two questionnaires. Spearman
      correlations were calculated between dietary intake and the corresponding
      biomarkers (serum carotenoids, tocopherols, and erythrocyte fatty acids).
      Correlations with beta-carotene and beta-cryptoxanthin were significant in the 13
      and 14-y age group (r=0.220-0.333, p<0.030) and the 10- and 11-y age subgroup
      who answered the questionnaire with assistance (r=0.295-0.299, respectively,
      p=0.006). Consumption of green-yellow vegetables and fruits was significantly
      correlated with beta-carotene and beta-cryptoxanthin levels (r=0.205-0.341,
      p<0.047). In the 13- and 14-y age group, correlations with eicosapentaenoic and
      docosahexaenoic acids were between 0.215 and 0.473 (p<0.040). Total seafood
      intake was significantly correlated with marine n-3 polyunsaturated fatty acids
      (PUFAs; r=0.239-0.420, p<0.023). In the 10- and 11-y age subgroup who completed
      the questionnaire with assistance, seafood intake was significantly correlated
      with marine n-3 PUFAs (r=0.239-0.243, p<0.032). In conclusion, dietary intake
      assessed using the BDHQ reflects the corresponding biomarkers for 13- and 14-y
      olds; however, when used for elementary school children, caution is necessary in
      interpreting the results.

PMID- 19602832
TI  - Mannitol lowers fat digestibility and body fat accumulation in both normal and
      cecectomized rats.
AB  - Mannitol is a six-carbon sugar alcohol that is widely distributed in plants.
      Sugar alcohols are widely used in various food products because of their numerous
      beneficial health effects. The present study investigated the effects of mannitol
      consumption on digestion, large gut fermentation and nutrient metabolism in
      normal and cecectomized male Wistar rats. After 28 d of feeding with three kinds
      of diet containing 0, 4 or 8% mannitol, mannitol consumption dose-dependently
      lowered the digestibilities of crude fat and crude protein, the ratio of body fat
      accumulation to energy absorbed and the hepatic and serum triglyceride levels in
      normal rats. After 24 d of feeding with three kinds of diet comprising a control
      diet, a 5% mannitol-containing diet and a 5% fructooligosaccharides (FOS)
      containing diet, mannitol lowered the digestibility of fat and the ratio of body
      fat accumulation to energy consumed and absorbed in cecectomized rats. On the
      other hand, FOS consumption had no effect on the accumulation of body fat, but
      lowered the digestibility of fat. FOS consumption greatly improved the
      accumulation of body ash in cecectomized rats. These results suggest that
      mannitol has a lowering effect on body fat accumulation, and further indicate
      that the cecum is not essential for the appearance of effects of mannitol on
      digestion, absorption and metabolism.

PMID- 19602833
TI  - Dietary soy protein isolate and its undigested high molecular fraction upregulate
      hepatic ATP-binding cassette transporter G5 and ATP-binding cassette transporter
      G8 mRNA and increase biliary secretion of cholesterol in rats.
AB  - Dietary soy protein isolate (SPI) and its undigested high molecular fraction
      (HMF) exhaustively digested with proteases, compared with casein (CAS),
      significantly reduced serum and liver cholesterol concentration in rats. Biliary
      excretion of cholesterol was significantly higher in rats fed SPI and HMF than in
      those fed CAS. Hepatic expression of ATP-binding cassette transporter G5 (ABCG5)
      and ATP-binding cassette transporter G8 (ABCG8) mRNA was significantly higher in
      rats fed SPI and HMF than in those fed CAS. These observations suggest that
      increased biliary excretion of cholesterol in SPI and HMF groups is caused by the
      enhanced expression of Abcg5/Abcg8.

PMID- 19602834
TI  - Confirmation of diabetes-related quantitative trait loci derived from SM/J and
      A/J mice by using congenic strains fed a high-carbohydrate or high-fat diet.
AB  - The interaction between causative genes and diet is known to influence the onset
      of obesity and diabetes in humans, although it has remained difficult to identify
      diabetogenic gene(s) because humans are genetically and environmentally
      heterogeneous. Mouse SMXA recombinant inbred (RI) strains are established from
      parental inbred strains (SM/J and A/J) and have been shown to be beneficial tools
      for analyzing polygenic traits. We previously mapped a significant quantitative
      trait locus (QTL, T2dm1sa) on Chromosome (Chr.) 10 and suggestive QTLs on Chr. 2,
      6, and 18 for diabetes-related traits by using SMXA RI strains fed a high
      carbohydrate diet. As a first step in identifying the responsible gene among QTLs
      for glucose tolerance mapped on Chr. 10 and 18, we established new strains of
      A.SM-T2dm1sa and SM.A-D18Mit19-D18Mit7 congenic mice. Each congenic strain bears
      the diabetogenic allele of an introgressed chromosomal region on a genetic
      background strain carrying the non-diabetogenic allele. The diabetogenic effect
      of T2dm1sa mapped on Chr. 10 was not supported by studies of A.SM-T2dm1sa
      congenic mice when the mice were fed a high-carbohydrate or high-fat diet. SM.A
      D18Mit19-D18Mit7 congenic mice showed impaired glucose tolerance not only when
      they were fed a high-carbohydrate diet, but also when they were fed a high-fat
      diet. Thus, it appears that gene(s) affecting diabetes-related traits under
      either dietary condition may be present on Chr. 18.

PMID- 19602835
TI  - Inhibition of collagenolytic cathepsins by beta-lactoglobulin in milk and its
      suppressive effect on bone resorption.
AB  - It is well known that the collagenolytic cathepsins play an important role in the
      degradation of bone matrix. Therefore, the purpose of this study was to clarify
      the prevention effect of bone resorption by milk components. Using double-layer
      reverse zymography, we found a 20 kDa protein in milk which inhibited cysteine
      proteases. This inhibitory protein was identified as beta-lactoglobulin B. The
      inhibitory activity of beta-lactoglobulin B against cathepsin K was stronger than
      that of beta-lactoglobulin A. Beta-lactoglobulin B specifically inhibited papain
      type cysteine proteases such as cathepsins K and L, but not serine proteases,
      aspartic proteases or metallo proteases. Beta-lactoglobulin B inhibited cathepsin
      K non-competitively and the Ki value was 10(-5) M. The formation of osteoclastic
      pits in the culture system was effectively inhibited by 10(-4)-10(-5) M beta
      lactoglobulin B in vitro. Furthermore, we demonstrated that beta-lactoglobulin B
      inhibited degradation of type I-collagen by collagenolytic cathepsins. Using the
      everted-sac method in rat small intestines, it was found that beta-lactoglobulin
      was more easily absorbed from the intestines of young rats (5 wk-old) than from
      those of older rats (more than 20 wk-old). The digested products of beta
      lactoglobulin B with lysyl-endopeptidase showed a similar inhibitory activity
      against cathepsin K to the intact beta-lactoglobulin B did. Therefore, peroral
      intake of beta-lactoglobulin in milk and its digested peptides are expected to
      help protect osteoclastic bone resorption via inhibition of collagenolytic
      cathepsins K and L.

PMID- 19602836
TI  - Oral administration of lactic acid bacteria isolated from traditional South Asian
      fermented milk 'dahi' inhibits the development of atopic dermatitis in NC/Nga
      mice.
AB  - We investigated the suppressive effect of lactic acid bacteria (LAB) isolated
      from traditional South Asian fermented milk 'dahi' on the development of atopic
      dermatitis (AD) using NC/Nga AD model mice. In the initial evaluation, we
      confirmed the effect of LAB on serum total IgE using ovalbumin (OVA)-induced type
      1 allergy model mice. Forty-one bacterial strains isolated from dahi were
      evaluated for their ability to induce interleukin (IL)-12 production and suppress
      IL-4 production in splenocytes obtained from OVA-sensitized mice. Of the 41
      strains tested, Lactobacillus delbrueckii subsp. lactis R-037 exhibited the
      greatest IL-12 induction, suggesting that it is a potent Th1 inducer. Oral
      administration of heat-treated R-037 significantly suppressed the elevation of
      serum total IgE in OVA-induced type 1 allergy model mice. In NC/Nga AD model
      mice, oral administration of heat-treated R-037 reduced inflammatory auricular
      thickness and alleviated the AD clinical score although the effect on serum total
      IgE level was unclear. Histopathological findings showed a tendency toward
      improvement of inflammation. Hyperkeratosis in particular showed improvement in
      dermatitis skin lesions. These results suggest that oral administration of R-037
      may alleviate AD.

PMID- 19602837
TI  - Consideration of diurnal variations in human blood NAD and NADP concentrations.
AB  - The sum of the urinary excretion of nicotinamide and its catabolites, which are
      metabolites of NAD and NADP, were observed to have clear diurnal variations in
      human urine. Then, we examined whether NAD and NADP in blood also showed the
      diurnal variation. All subjects were housed in the same facility and given the
      same diet during the experiment. In addition, we examined whether diurnal
      variations were affected by the intakes of dietary nicotinamide or not. As a
      result, neither the NAD nor the NADP content of the blood shows the diurnal
      variation regardless of the administered amount of nicotinamide. The
      concentrations of NAD and NADP did not increase according to the intake of
      nicotinamide. The existence of a mechanism by which NAD and the NADP levels of
      the blood are constantly maintained by the adjustment of the amount of excretion
      to the urinary bladder, was suggested.

PMID- 19602838
TI  - Acute effects of dihydrocapsaicin and capsaicin on the distribution of white
      blood cells in rats.
AB  - The acute effects of dihydrocapsaicin (DHC) and capsaicin (CAP) on the number of
      white blood cells (WBCs), neutrophils, eosinophils, basophils, monocytes,
      lymphocytes, T lymphocytes, B lymphocytes and NK cells, and serum corticosterone
      levels were studied in rats. Male 7-wk-old SD rats were divided into DHC (3.0
      mg/kg BW), CAP (3.0 mg/kg BW) and control (CON) groups. The number of total WBCs
      was 1.30-1.42 times significantly higher in the DHC group than in the CON group
      at 6-12 h. The number of neutrophils was 1.62 times significantly higher in the
      DHC group than in the CON group at 12 h. The number of total WBCs and
      neutrophils, however, showed no significant changes between the CAP and CON
      groups. The number of lymphocytes was 0.61 and 0.70 times significantly lower in
      the DHC and CAP groups than in the CON group at 3 h. The number of T lymphocytes
      and B lymphocytes was 0.74 and 0.54 times lower in the DHC group than in the CON
      group, respectively. CAP, however, did not significantly change the number of T
      lymphocytes or B lymphocytes. No significant changes in the number of NK cells
      were observed among the three groups. CAP and DHC did not change the number of
      monocytes, eosinophils or basophils. No significant changes of the serum
      corticosterone levels were observed among the three groups. In conclusion,
      capsaicinoids decreased the number of acquired immunity cells, and increased the
      number of total WBCs and neutrophils without changing the number of monocytes,
      eosinophils or basophils. The magnitude of these effects was relatively higher in
      DHC than in CAP.

PMID- 19602839
TI  - Effects of squat exercise and branched-chain amino acid supplementation on plasma
      free amino acid concentrations in young women.
AB  - The present study was conducted to examine alterations in plasma free amino acid
      concentrations induced by squat exercise and branched-chain amino acid (BCAA)
      supplementation in young, untrained female subjects. In the morning on the
      exercise session day, participants ingested drinks containing either BCAA
      (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body
      weight 15 min before a squat exercise session, which consisted of 7 sets of 20
      squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA
      concentrations were decreased subsequent to exercise, whereas they were
      significantly increased in the BCAA trial until 2 h after exercise. Marked
      changes in other free amino acids in response to squat exercise and BCAA
      supplementation were observed. In particular, plasma concentrations of methionine
      and aromatic amino acids were temporarily decreased in the BCAA trial, being
      significantly lower than those in the placebo trial. These results suggest that
      BCAA intake before exercise affects methionine and aromatic amino acid
      metabolism.

PMID- 19602840
TI  - Development of a method for the determination of gamma-aminobutyric acid in
      foodstuffs.
AB  - A method for the determination of gamma-aminobutyric acid (GABA) in foodstuffs
      has been developed by combination of its dinitrophenylation and high-performance
      liquid chromatography (HPLC) using norleucine as an internal standard. GABA was
      converted to its stable derivative with 1-fluoro-2,4-dinitrobenzene and the
      derivative was extracted with ether. After evaporation of the extract, the
      residue was dissolved in 0.1 M NaOH and the solution was subjected to reversed
      phase HPLC with an elution system of a linear gradient of methanol in 10 mM Tris
      HCl buffer (pH 6.0) and a detection system monitoring the absorbance of the
      effluent at 400 nm. The present method was shown to be utilized as a satisfactory
      method for the determination of gamma-aminobutyric acid in foodstuffs.

PMID- 19602841
TI  - Preparation of fresh cheese from caprine milk as a model for the reduction of
      allergenicity.
AB  - Fresh cheese was prepared from caprine milk by isoelectric precipitation as a
      model experiment for reducing the allergenicity of milk. After acidic
      precipitation of casein, the beta-lactoglobulin content in curd was determined by
      ELISA using monoclonal antibody (MAb-beta209). The beta-lactoglobulin content was
      very high in the fresh cheese obtained from heat-treated (85 degrees C) bovine or
      caprine milk, while that obtained from untreated milk contained none of this
      protein. Taking it into account that caprine milk has only a small amount of
      alpha(s1)-casein, one of the major bovine milk allergens, the caprine fresh
      cheese sterilized after processing by precipitation may be useful as a protein
      source of low allergenicity.

PMID- 19602842
TI  - Improved swimming pool achieves higher reproducibility and sensitivity to effect
      of food components as ergogenic AIDS.
AB  - A previously developed current swimming pool for mice has been used to evaluate
      many food components that enhance endurance exercise performance. In this
      article, to improve reproducibility, reliability and sensitivity of this assay
      system, we improved the spout part to generate a uniform current and divided the
      pool into six lanes to avoid physical interference between swimming mice. The
      stability of the current flow was assessed by measuring the surface current speed
      and water volume from the spout part. Maximum swimming times of ddY and BALB/c
      mice were measured to assess the reproducibility of the maximum swimming time.
      The improvement in sensitivity compared to the original equipment was estimated
      under three physiological conditions: low carbohydrate diet feeding, low blood
      hemoglobin level, and carbohydrate supplementation during exercise. The new spout
      part improved uniformity and quick adjustment of surface current, yielding an
      increase of workload in a stepwise manner during swimming. Exercise workload was
      increased in proportion to surface current speed, as evidenced by cadence of
      kicks and serum lactic acid levels. The improved swimming pool showed higher
      reproducibility of swimming time until fatigue (p<0.0001). Correspondence between
      blood hemoglobin concentration and swimming time was improved in the swimming
      pool. The improved swimming pool yielded higher sensitivity for low carbohydrate
      diet feeding (p<0.0001) and carbohydrate supplementation during exercise (p<0.01)
      compared to the original swimming pool. The improvement of the swimming pool
      achieved higher sensitivity and reproducibility in assessing various diet and
      food components compared to the original swimming pool.

PMID- 19602843
TI  - Recovery of cognitive performance and fatigue after one night of sleep
      deprivation.
AB  - OBJECTIVES: The aim of this study was to investigate how subjective sleepiness,
      mood states, simple and high-order cognitive performance change after one night
      of sleep deprivation (SD) and recover to after 7 h normal recovery sleep
      opportunity during three recovery days. METHODS: Ten healthy subjects
      participated in this study. We measured their subjective sleepiness, mood states
      and their performances of 2 simple tasks and 4 high-order cognitive tasks twice a
      day for 5 days, on the baseline day, post-vigil day and 3 recovery days after SD.
      This study was conducted considering each participant's motivation for task,
      learning effect and diurnal variation of performance. RESULTS: The performances
      of simple tasks such as addition or short-term memory were not reduced after SD
      and were the poorest on the baseline day, and improved gradually; however the
      high-order cognitive performances were at their lowest on the post-vigil day and
      needed 2 recovery sleep opportunities to return to the baseline level. Fatigue
      and confusion in mood states and subjective sleepiness were also at their lowest
      after SD. Subjective sleepiness nearly recovered to the baseline level on the 1st
      recovery day, but fatigue and confusion reached the baseline levels on the 2nd
      recovery day. CONCLUSION: These results suggest that cognitive deterioration and
      the recovery process may differ between simple task performance and high-order
      cognitive task performance, which needed 2 ordinary sleep opportunities to
      recover to the baseline level, and the change of subjective mood states were also
      different for each mood.

PMID- 19602845
TI  - Tumor necrosis factor-alpha (TNF-alpha) induces upregulation of RhoA via NF
      kappaB activation in cultured human bronchial smooth muscle cells.
AB  - RhoA plays an important role in Ca(2+) sensitization of bronchial smooth muscle
      in antigen-induced airway hyperresponsiveness (AHR). Tumor necrosis factor-alpha
      (TNF-alpha), a major proinflammatory cytokine, is capable of inducing AHR, but
      the mechanisms for this are still unknown. In the present study, the effect of
      TNF-alpha on RhoA protein expression was examined in cultured human bronchial
      smooth muscle cells (hBSMCs). To investigate the role of NF-kappaB in the TNF
      alpha-induced upregulation of RhoA, the effects of an inhibitor of IkappaB kinase
      (IKK), BMS-345541, were also determined. Both immunoblot and immunocytochemical
      analyses revealed that incubation of the hBSMCs with TNF-alpha caused an
      activation of NF-kappaB (determined by a translocation of p65 proteins to
      nuclei): the peak response was observed when cells were incubated with 10 ng/mL
      of TNF-alpha for 30 min. An upregulation of RhoA protein was also observed at 12 
      24 h after the incubation with TNF-alpha (10 ng/mL). Both the activation of NF
      kappaB and upregulation of RhoA were concentration-dependently inhibited by the
      co-incubation with BMS-345541. These results suggest that TNF-alpha-induced
      upregulation of RhoA might be mediated by an activation of NF-kappaB in hBSMCs.

PMID- 19602844
TI  - Endogenous and exogenous glucocorticoids prevent trimethyltin from causing
      neuronal degeneration of the mouse brain in vivo: involvement of oxidative stress
      pathways.
AB  - The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the
      murine brain. Earlier studies indicate that TMT-induced neuronal degeneration is
      enhanced by adrenalectomy. However, no evaluation has been attempted to determine
      the mechanism underlying the enhancement of TMT neurotoxicity by adrenalectomy
      and its implications in neuronal degeneration. To assess the implications and
      determine the mechanism of adrenalectomy-elicited enhancement of TMT
      neurotoxicity, we examined neuronal degeneration and associated signaling
      pathways in adrenalectomized mice. Adrenalectomy dramatically enhanced the TMT
      induced neuronal damage in certain brain regions including the dentate gyrus,
      olfactory bulb, and anterior olfactory nucleus, in addition to exacerbating the
      behavioral abnormalities. TMT-induced activation of caspase-3 and calpain was
      also enhanced by adrenalectomy. The above events elicited by TMT were almost
      entirely prevented by treatment with dexamethasone. In addition to the above
      events, adrenalectomy clearly enhanced the activation of c-Jun-N-terminal kinases
      and the formation of 4-hydroxynonenal in the dentate gyrus following TMT
      treatment. The dentate granule cell damage induced by TMT was exacerbated by
      mifepristone, a glucocorticoid-receptor antagonist. Taken together, our data
      suggest that endogenous and exogenous glucocorticoids prevent neurodegeneration
      induced by TMT in the central nervous system by attenuating intensive oxidative
      stress and associated signaling pathways.

PMID- 19602846
TI  - Effect of mosapride citrate hydrate on the colon cleansing action of polyethylene
      glycol electrolyte lavage solution (PEG-ELS) in guinea pigs.
AB  - Polyethylene glycol electrolyte lavage solution (PEG-ELS) is widely used for
      colon cleansing prior to colonoscopy and colonic surgery. It has recently been
      shown that coadministration of PEG-ELS and mosapride citrate hydrate (mosapride),
      a selective 5-HT(4)-receptor agonist, is clinically useful for barium enema
      examination as it allows adequate barium coating. However, there is no report
      showing that mosapride has beneficial effects on colon cleansing and its
      underlying mechanism in experimental animals. In the present study, we
      investigated the effects of mosapride on colonic transit and on the colon
      cleansing action of PEG-ELS in guinea pigs. Mosapride (10 - 20 mg/kg, i.g.)
      significantly enhanced colonic transit rate in guinea pigs. Although PEG-ELS
      alone showed adequate colon cleansing action, excess fluid remained in the colon.
      Coadministration of mosapride (20 mg/kg) and PEG-ELS, regardless of mosapride
      timing, reduced colonic content weight (dry residue and water amount) as compared
      to PEG-ELS alone. These findings suggest that mosapride enhances the colon
      cleansing action of PEG-ELS via an increase in colonic transit in guinea pigs,
      that is, it reduces not only fecal residue but also excessive fluid in the
      colonic lumen. It is therefore believed that coadministration of mosapride and
      PEG-ELS can allow better visualization in barium enema examination.

PMID- 19602847
TI  - Gene expression in mouse preimplantation embryos affected by apoptotic inductor
      actinomycin D.
AB  - The aim of this study was to test the effect of actinomycin D on the expression
      of selected genes and to elucidate possible components of its apoptotic pathway
      in mouse embryos. Selected mRNAs and Trp53 protein were examined in blastocysts
      cultured for 24 h in vitro with or without the presence of a high concentration
      of actinomycin D. In all tested genes, the relative quantities of mRNA were
      significantly lower in treated blastocysts than in controls. The mRNA quantities
      of H2afz, Actb, Bax, Bad and Bcl2 were reduced at a similar rate, but the
      decreases in Bcl2l2 and Trp53 mRNA were significantly greater. Treatment with
      actinomycin D also changed the ratio between the mRNA levels of some pro
      apoptotic and anti-apoptotic genes: the Bad/Bcl2l2 and the Bax/Bcl2l2 ratios were
      on average 4.39 and 2.66 times higher in the treated embryos than in the
      controls, respectively. Generally, treatment led to developmental arrest and
      significant increase in the incidence of cells with typical apoptotic features.
      However, its effect on Trp53 protein expression was not significant. The results
      suggest that mechanisms beyond the apoptotic effect of actinomycin D might
      include specific changes in the expression of pro-apoptotic and anti-apoptotic
      genes, shifting the expression ratio in favor of the pro-apoptotic ones. The
      results also show that the role of Trp53 is probably not crucial in this
      apoptotic pathway.

PMID- 19602848
TI  - Comparative changes in the serum concentrations of inhibin-B, prolactin,
      gonadotropins and steroid hormones at different reproductive States in domestic
      Turkey hens.
AB  - The present study was undertaken to compare the changes in circulating levels of
      inhibin-B, prolactin, follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), estradiol-17beta, progesterone and testosterone during the different
      reproductive states of turkey hens. Blood samples were collected during different
      reproductive states, at laying, incubating and out of lay. Inhibin-B was measured
      by ELISA, while other hormones were determined by Chemiluminescent Microparticle
      Immunoassay (CMIA). The results revealed highly significant differences among the
      hen's states for all serum hormone concentrations. The highest levels of inhibin
      B and prolactin were observed in incubating hens, while the lowest values were
      observed in laying hens. In contrast, the highest levels of FSH, LH, estradiol
      17beta, progesterone and testosterone were found in the laying group, while the
      lowest values were found in the incubating group. The progesterone level was
      higher in the laying group compared with the other groups. These results clearly
      demonstrate that negative correlation was found between both the inhibin-B and
      prolactin levels and the gonadotropin and steroid hormone concentrations during
      the different reproductive states of the turkey hens. In addition, the results
      suggest that inhibin-B may be involved in control of FSH and LH secretion.

PMID- 19602849
TI  - Angiotensin II secretion by the bovine oviduct is stimulated by luteinizing
      hormone and ovarian steroids.
AB  - Angiotensin II (Ang II), a vasoactive peptide, is secreted by the bovine oviduct
      and is involved in modulation of local oviductal contraction. Ang II biosynthesis
      and release during the normal estrous cycle and the effects of luteinizing
      hormone (LH) and ovarian steroids on biosynthesis and secretion of Ang II were
      investigated. During the preovulatory period, increases in mRNA expression for
      Angiotensin converting enzyme 1 (ACE-1) and release of Ang II peptide were
      detected. Microdialysis of oviductal segments in vitro showed that LH alone
      significantly increased Ang II release, and combined infusion of LH+E(2)+P(4)
      caused an increase in Ang II release. In cultured oviductal epithelial cells, LH
      increased Ang II release and ACE-1 mRNA expression, and E(2)+P(4) enhanced
      stimulatory effect of LH on Ang II release and ACE-1 mRNA expression. Thus, it
      can be concluded that the oviductal Ang II system is upregulated by LH and
      ovarian steroids during the periovulatory period and may enhance local oviductal
      contraction. These events could stimulate transport of gametes to the
      fertilization site.

PMID- 19602850
TI  - Sex-reversed somatic cell cloning in the mouse.
AB  - Somatic cell nuclear transfer has many potential applications in the fields of
      basic and applied sciences. However, it has a disadvantage that can never be
      overcome technically-the inflexibility of the sex of the offspring. Here, we
      report an accidental birth of a female mouse following nuclear transfer using an
      immature Sertoli cell. We produced a batch of 27 clones in a nuclear transfer
      experiment using Sertoli cells collected from neonatal male mice. Among them, one
      pup was female. This "male-derived female" clone grew into a normal adult and
      produced offspring by natural mating with a littermate. Chromosomal analysis
      revealed that the female clone had a 39,X karyotype, indicating that the Y
      chromosome had been deleted in the donor cell or at some early step during
      nuclear transfer. This finding suggests the possibility of resuming sexual
      reproduction after a single male is cloned, which should be especially useful for
      reviving extinct or endangered species.

PMID- 19602851
TI  - A comparative study of protein kinase C activation in gamma-irradiated
      proliferating and confluent human lung fibroblast cells.
AB  - Exposure to low doses of radiation has been recently proven to be much more
      mutagenic and carcinogenic than previously thought. Since radiation sensitivity
      varies with different phases of cell cycle, we have investigated the activation
      of protein kinase C (PKC) after low doses (0.10-1 Gy) of gamma-irradiation on
      proliferating (log) and non-proliferating (confluent/plateau) human normal lung
      fibroblast (MRC-5) cells. PKC isoforms have been shown to play key roles in the
      regulation of proliferation, differentiation, migration and survival. In this
      study, we have examined the activation of phosphorylated forms of PKC isoforms
      (PKC-betaII, PKC-alpha/beta, PKC-theta) and non-phosphorylated PKC-alpha in an
      attempt to understand its kinases in total and subcellular (cytosolic and
      nuclear) fractions. Cytosolic fraction of the log phase cells showed an increase
      in activity of PKC-betaII, PKC-alpha/beta and PKC-theta with the radiation dose.
      However, in the nuclear fraction, PKC-betaII and PKC-theta showed higher activity
      than the PKC-alpha/beta. In the plateau phase cells of the cytosolic fraction,
      PKC-betaII showed higher activity than the PKC-alpha/beta and PKC-theta isoforms.
      Furthermore, in the nuclear fraction PKC-betaII and PKC-alpha/beta isoforms
      showed higher activity than the PKC-theta. In total cellular protein of the log
      phase cells, a dose dependent increase in PKC-betaII activity followed by PKC
      alpha/ beta was observed and in the plateau phase of cells, PKC-betaII showed
      higher activity than the PKC-alpha/ beta. The specific activation of PKC isoforms
      in the plateau phase cells, as demonstrated for the first time, may help us to
      understand the radiation induced initiation of cellular transformation like hyper
      proliferative phenotype, if any.

PMID- 19602852
TI  - Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine
      induced contraction of guinea pig ileum and on histamine release from mast cells.
AB  - The medical mechanism against type I allergies is to block the release or
      production of chemical mediators from mast cells or to block the H(1)-receptor
      signaling. We previously reported that the anti-allergic action of the dry powder
      from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine
      (eMMBP) was dependent on the inhibition of histamine release from mast cells.
      Here, we investigate that the effect of fractions in eMMBP on the histamine
      induced contraction in guinea pig ileum and on the release of histamine in rat
      peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is
      dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor.
      Fractions contained caffeic acid, caffeoylquinic acid and fractions contained
      flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release
      from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin
      suppress the histamine-induced contraction in guinea pig ileum. Moreover, the
      histamine-induced contraction was not affected by caffeic acid, however, such
      contraction was significantly inhibited by rutin. These results suggest that the
      primary antagonists of H(1)- receptor are different from the components in eMMBP
      that inhibit histamine release, and that these components participate in the anti
      allergic activity of eMMBP.

PMID- 19602853
TI  - Differential involvement of alpha1-adrenoceptors in vasoconstrictor responses to
      cooling in mouse plantar arteries in vitro and in vivo.
AB  - Cooling-induced reduction of skin blood flow results from a reflex increase in
      sympathetic output and an enhanced vasoconstrictor activity of skin vessels. The
      latter has been proposed to be mediated by increased reactivity of alpha(2C)
      adrenoceptors during cooling in studies with isolated cutaneous vessels in vitro.
      We have previously shown in studies with tetrodotoxin-treated mice in vivo that
      reduction of plantar skin blood flow (PSBF) induced by local cooling results
      primarily from increased reactivity of alpha(2C)-adrenoceptors. In addition, we
      showed that part of the cooling-induced response was also mediated by alpha(1)
      adrenoceptors. However, the mechanisms involved in the cooling-induced responses
      mediated by alpha(1)-adrenoceptors have not been elucidated. The present study is
      an investigation seeking to clarify the mechanisms involving alpha(1)
      adrenoceptors. Medial plantar arteries were isolated from male ddY mice and
      changes in vessel diameter were measured in vitro using pressurized
      arteriography. In vivo measurements of PSBF were performed on artificially
      ventilated tetrodotoxin treated mice, anaesthetized with pentobarbital sodium,
      using laser Doppler flowmetry, with the probe positioned above the medial plantar
      artery. In the in vitro studies with isolated plantar arteries, cooling from 37
      to 28 degrees C did not affect the constrictor potency of phenylephrine, an
      alpha(1)-adrenoceptor agonist, and the threshold concentration to evoke
      constriction was rather higher at 28 degrees C than it was at 37 degrees C. The
      cooling also suppressed the constrictor efficacy of UK14,304, an alpha(2)
      adrenoceptor agonist. In contrast, cooling the air temperature around the foot
      from 25 to 10 degrees C in vivo decreased PSBF, which was significantly inhibited
      by phentolamine, an alpha-adrenoceptor antagonist, although MK-912, an alpha(2C)
      adrenoceptor antagonist, had no effect on it. These results suggest that although
      alpha(1)-adrenoceptors are involved in cooling-induced reduction of PSBF in mice,
      the response is unlikely to result from an enhancement of alpha(1)-adrenoceptor
      mediated vasoconstriction of plantar arteries during cooling.

PMID- 19602854
TI  - Functional importance of the cytoskeletal protein in acetylcholine-induced
      contraction of rat bronchial smooth muscle.
AB  - The contractile capacity of smooth muscle cells depends on the cytoskeletal
      framework of the cell. The aim of this study was to determine the functional
      importance of the microtubule, actin filament and intermediate filament
      components of the cytoskeleton in acetylcholine (ACh)-induced contractile
      responses of the rat isolated bronchial smooth muscle. The expressions of alpha
      actin, beta-actin, alpha-tubulin, desmin and vimentin were observed by
      immunoblotting in rat bronchial tissues. alpha-Actin and desmin were
      immunohistochemicaly observed in smooth muscle layer. Cytochalasin D, latrunculin
      A (inhibitors of the actin cytoskeleton) and acrylamide (an inhibitor of the
      intermediate filament) significantly decreased the contractions induced by ACh in
      concentration-dependent manners. On the other hand, colchicine or nocodazole
      (inhibitors of the microtubule cytoskeleton) had no effect on the ACh-induced
      contraction. These findings suggest that the contraction induced by ACh is highly
      dependent on polymerization of actin and intermediate filament, such as desmin,
      but not on the polymerization of microtubule in rat bronchial smooth muscle.

PMID- 19602855
TI  - Modulation of slow waves by transmural nerve stimulation of smooth muscle tissue
      isolated from the corpus of the guinea-pig stomach.
AB  - Modulation of slow waves in response to transmural nerve stimulation (TNS) was
      investigated in smooth muscle preparations isolated from the corpus of the guinea
      pig stomach. Single TNS evoked an inhibitory junction potential (i.j.p.) and
      enhanced the amplitude of the following slow wave. Effects of atropine, N(omega)
      nitro-L-arginine (L-NA) and apamin revealed that corpus smooth muscle was
      innervated by cholinergic excitatory, nitrergic inhibitory and apamin-sensitive
      inhibitory nerves. In preparations isolated from the upper corpus which generated
      slow waves of 5-15 mV amplitude, a 1 min train of TNS (0.5 or 1 Hz frequency)
      increased the amplitude, with further enhancement by L-NA, but inhibition by
      atropine. In the lower corpus, larger amplitude (20-30 mV) slow waves were
      generated but these were not altered by a TNS train. However, application of L-NA
      and neostigmine, or often L-NA alone, resulted in increased frequency and
      decreased amplitude of slow waves during TNS, with an associated depolarization
      of the membrane. These changes were inhibited by atropine. In the presence of
      atropine, TNS reduced slow wave amplitude in an L-NA-sensitive manner.
      Acetylcholine (ACh) at 1 nM increased the amplitude of slow waves in the upper
      corpus. In the lower corpus, while low concentrations of ACh (<10 nM) did not
      increase the frequency and decrease the amplitude of slow waves with an
      associated depolarization of the membrane, this occurred at high concentrations
      of ACh (>10 nM). Application of the NO donor, sodium nitroprusside (SNP, 10 nM-1
      microM), reduced the amplitude of slow waves. The changes in amplitude of slow
      waves elicited by ACh or SNP were not associated with a significant change in
      frequency. These results indicate that in the corpus circular smooth muscle,
      neural modulation of slow waves appeared to be exerted mainly on the amplitude,
      but not on the frequency.

PMID- 19602856
TI  - Effect of N-epsilon-(carboxymethyl)lysine on coronary vasoconstriction in
      isolated perfused hearts from control and streptozotocin-induced diabetic rats.
AB  - Advanced glycation end products (AGEs) derived from glucose are implicated in the
      pathogenesis of diabetic vascular disease. However, their direct modulatory
      effects on coronary vascular tone remain unclear. We previously reported that
      coronary vasoconstriction was induced by acetylcholine (ACh) infusion of the
      isolated perfused rat heart and that sensitivity was greater in perfused hearts
      from streptozotocin (STZ)-induced diabetic rats than in those from age-matched
      controls (Kamata et al., 2008). Here, we investigated the effect of N(epsilon)
      (carboxymethyl)lysine (CML), which has one of the main AGE structures, on ACh
      induced vasoconstriction in perfused hearts isolated from control and diabetic
      rats. ACh-induced vasoconstriction was significantly greater in the STZ-induced
      diabetic group than in the age-matched controls. CML enhanced the ACh-induced
      vasoconstriction in coronary arteries from control rats, but not in those from
      STZ-induced diabetic rats. In the controls, the vasoconstriction induced by the
      calcium-channel activator Bay K 8644 was also enhanced by CML. These CML-mediated
      enhancements of the vasoconstrictions induced by ACh and Bay K 8644 were
      significantly suppressed by tempol, a superoxide dismutase mimetic. The plasma
      CML and glucose levels were each significantly elevated in STZ-induced diabetic
      rats. These findings suggest (a) that CML augments ACh-induced coronary
      vasoconstriction, an effect that may be attributable to increased superoxide and
      to activation of voltage-gated Ca(2+) channels and (b) that this modulating
      effect may be desensitized in the STZ-induced diabetic heart.

PMID- 19602857
TI  - [Effects of the reconstitution and storage conditions of powdered infant formula
      (PIF) on the survival and growth of Enterobacter sakazakii].
AB  - The effect of the reconstruction and storage conditions of powdered infant
      formula (PIF) on the survival and growth of three Enterobacter sakazakii strains,
      ATCC 29004, HT 022 and HT 028, was investigated. D values of E. sakazakii ATCC
      29004 and HT 022 at 60 degrees C were 3.6 and 1.6 min, respectively, and that of
      HT 028 at 52 degrees C was 1.6 min. The effect of the temperature of the water
      used for the reconstruction of PIF on the inactivation of the three E. sakazakii
      strains was also investigated. One to 2 log order inactivation occurred at 70
      degrees C, and above 5 log order inactivation at 80 degrees C. Storage tests at
      5, 10 and 25 degrees C showed that none of the strains could grow at 5 degrees C,
      HT 028 grew slightly at 10 degrees C, and at 25 degrees C all three strains
      started growth after 4 hr incubation and reached up to 8 log CFU/mL after 16 hr
      incubation. From the above results, it is concluded that a suitable temperature
      of the hot water for reconstruction of PIF is above 70 degrees C, and the
      preferred storage temperature of reconstructed PIF, which is recommended to be
      consumed within 2 hr, is below 5 degrees C.

PMID- 19602858
TI  - Development of quantitative duplex real-time PCR method for screening analysis of
      genetically modified maize.
AB  - A duplex real-time PCR method was developed for quantitative screening analysis
      of GM maize. The duplex real-time PCR simultaneously detected two GM-specific
      segments, namely the cauliflower mosaic virus (CaMV) 35S promoter (P35S) segment
      and an event-specific segment for GA21 maize which does not contain P35S.
      Calibration was performed with a plasmid calibrant specially designed for the
      duplex PCR. The result of an in-house evaluation suggested that the analytical
      precision of the developed method was almost equivalent to those of simplex real
      time PCR methods, which have been adopted as ISO standard methods for the
      analysis of GMOs in foodstuffs and have also been employed for the analysis of
      GMOs in Japan. In addition, this method will reduce both the cost and time
      requirement of routine GMO analysis by half. The high analytical performance
      demonstrated in the current study would be useful for the quantitative screening
      analysis of GM maize. We believe the developed method will be useful for
      practical screening analysis of GM maize, although interlaboratory collaborative
      studies should be conducted to confirm this.

PMID- 19602859
TI  - Survival of foodborne pathogens in grain products and the effect of catechins.
AB  - We investigated the survival of bacterial pathogens in grain products. Salmonella
      Enteritidis and Staphylococcus aureus survived for more than 3 weeks in grain
      flakes. Although S. Enteritidis in grain flakes reached a level of less than
      10(2) CFU/g, the surviving organisms grew rapidly in milk and reached 10(9) CFU/g
      after 25-hr incubation. When catechins were present on the grain flakes, the
      numbers of S. Enteritidis and S. aureus were significantly decreased. In
      addition, catechins reduced the survival and growth of S. Enteritidis, S. aureus
      and Bacillus cereus when added to cooked grain products. This study indicates
      that S. Enteritidis, S. aureus and Bacillus can survive for a long time in grain
      products and that catechins impair their survival and growth.

PMID- 19602860
TI  - [Determination of melamine in Chinese-made processed food].
AB  - A method using liquid chromatograph coupled with tandem mass spectrometer
      (LC/MS/MS) was developed for the determination of melamine in processed food.
      After extraction with 50% acetonitrile and clean-up with PSA and SCX, the
      quantification limit of melamine in processed food was 0.5 microg/g. The
      recoveries and relative standard deviations were 113 to 115% and less than 5%,
      respectively. Therefore, we considered that the developed method offers high
      precision and sensitivity for the determination of melamine in processed food.
      When the method was applied to six suspected products, 0.8 to 37 microg/g of
      melamine was detected from four milk-rich products.

PMID- 19602861
TI  - [Sample preprocessing method for residual quinolones in honey using
      immunoaffinity resin].
AB  - A sample preparation method was developed for determination of quinolones in
      honey using immunoaffinity resin. For this purpose, an immunoaffinity resin for
      quinolones was prepared by coupling a quinolone-specific monoclonal antibody to
      agarose resin. Honey samples diluted with phosphate buffer were reacted with
      immunoaffinity resin. After the resin was washed, quinolones were eluted with
      glycine-HCl. Quinolones in the eluate were determined by HPLC with fluorescence
      detection. No interfering peak was found on the chromatograms of honey samples.
      The recoveries of quinolones from samples were over 70% at fortification levels
      of 20 ng/g (for norfloxacin, ciprofloxacin and enrofloxacin) and 10 ng/g (for
      danofloxacin). The quantification limits of quinolones were 2 ng/g. This sample
      preprocessing method using immunoaffinity resin was found to be effective and
      suitable for determining residual quinolones in honey.

PMID- 19602862
TI  - [Contamination with genetically modified maize MON863 of processed foods on the
      market].
AB  - Genetically modified maize MON863 (MON863), which has passed a safety examination
      in Japan, is commercially cultivated in the United States as a food and a
      resource for fuel. Maize is an anemophilous flower, which easily hybridizes.
      However, an official method for quantifying the content of MON863 has not been
      provided yet in Japan. We here examined MON863 contamination in maize-processed
      foods that had no labeling indicating of the use of genetically modified
      maize.From March 2006 to July 2008, we purchased 20 frozen maize products, 8
      maize powder products, 7 canned maize products and 4 other maize processed foods.
      Three primer pairs named MON 863 primer, MON863-1, and M3/M4 for MON863-specific
      integrated cassette were used for qualitative polymerase chain reaction (PCR). A
      primer pair "SSIIb-3" for starch synthase gene was used to confirm the quality of
      extracted DNA. The starch synthase gene was detected in all samples. In
      qualitative tests, the MON863-specific fragments were detected in 7 (18%) maize
      powder products out of the 39 processed foods with all the three primer pairs.We
      concluded that various maize processed foods on the market were contaminated with
      MON863. It is important to accumulate further information on MON863 contamination
      in maize-processed foods that have no label indication of the use of genetically
      modified maize.

PMID- 19602863
TI  - [Survey of pesticide residues in imported vegetable products (1992.4-2006.3)].
AB  - Pesticide residues in 165 imported vegetable products on the Tokyo market from
      Apr. 1992 to Mar. 2006 were investigated. Seven kinds of pesticides were detected
      at levels between Tr (below 0.01 ppm) and 1.0 ppm from 16 samples. There was no
      sample in which pesticide residues exceeded the MRLs. The salt leaf of grape
      imported from Greece contained chlorpyrifos and quinalphos, and there was some
      doubt as to whether the residue levels exceeded the MRLs when the Japanese
      positive list system for pesticide residues in food was applied. Pesticides were
      detected from pickles and dehydrated vegetable, but not from products that had
      been treated with heat and water, such as boiled vegetables and purees. Many
      samples of products from Asia, and North America area contained detectable levels
      of pesticides. Residue levels of these pesticides were calculated as between
      0.006 and 20.3% of their ADI values according to the daily intake of vegetable
      products. Therefore, these vegetable products should be safe when eaten in a
      normal manner.

PMID- 19602864
TI  - Not without my permission: parents' willingness to permit use of newborn
      screening samples for research.
AB  - BACKGROUND: State newborn screening (NBS) programs are considering the storage
      and use of NBS blood samples for research. However, no systematic assessment of
      parents' attitudes exists. METHODS: We conducted an Internet-based survey of a
      nationally representative parent sample. We examined parents' willingness (1) to
      permit use of their children's NBS samples for research with/without their
      permission and (2) to allow NBS sample storage. Using bivariate and multinomial
      logistic regression, we examined the association of parent and child
      characteristics with parents' willingness to permit NBS sample storage and use
      for research, respectively. RESULTS: The response rate was 49.5%. If permission
      is obtained, 76.2% of parents were 'very or somewhat willing' to permit use of
      the NBS sample for research. If permission is not obtained, only 28.2% of parents
      were 'very or somewhat willing'. Of parents surveyed, 78% would permit storage of
      their children's NBS sample. Parents who refused NBS sample storage were also
      less willing to permit use of the NBS sample for research. CONCLUSIONS: Three
      quarters of parents would permit use of their children's NBS samples for research
      - if their permission is obtained. Parents not in favor of storing NBS samples
      often opposed the use of NBS samples for research.

PMID- 19602865
TI  - Out cold: biochemical regulation of mammalian hibernation - a mini-review.
AB  - Hibernating mammals offer an intriguing example of natural torpor and illustrate
      the regulatory mechanisms that control metabolic rate depression and the cell
      preservation strategies that support long-term viability in a hypometabolic
      state. These suggest applied strategies for improving the hypothermic
      preservation of human organs for transplant, and guidelines that could aid the
      development of torpor as an intervention strategy in human medicine. Recent
      advances in hibernation research have illustrated mechanisms that contribute to
      metabolic depression by orchestrating the global suppression of ATP-expensive
      transcription and translation including multiple forms of post-translational
      modification of proteins/enzymes (phosphorylation, acetylation, SUMOylation),
      mRNA storage mechanisms, and differential expression of microRNA species. DNA
      screening technologies have also contributed new advances in understanding the
      range of cell functions that are impacted during torpor and point out some
      critical preservation strategies that aid long-term viability in a torpid state.
      These include antioxidant defenses, chaperones and the implementation of the
      unfolded protein response, and the enhancement of serpins (serine protease
      inhibitors) to control the actions of extracellular proteases in clotting and
      inflammation responses.

PMID- 19602866
TI  - Solitary subungual keratoacanthoma arising in an MSH2 germline mutation carrier:
      confirmation of a relationship by immunohistochemical analysis.
AB  - BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal dominant disorder
      characterized by the concurrent or sequential development of at least 1 sebaceous
      gland tumor or keratoacanthoma and 1 or more internal malignancies. It is
      actually considered as a variant of hereditary nonpolyposis colorectal cancer
      (HNPCC) as both MTS and HNPCC are more often associated with germline mutations
      in the DNA mismatch repair (MMR) gene. OBJECTIVE AND METHODS: We report the case
      of MTS diagnosed after the occurrence of a solitary subungual keratoacanthoma
      (SKA) in a man with a well-known family history of HNPCC and who is carrying a
      constitutional 1-7 deletion in the MSH2 MMR gene. RESULTS: The link between the
      germline mutation and the skin tumor was reinforced by immunohistochemical
      staining. MSH2 immunoreactivity was decreased in SKA tumoral cells when compared
      to normal adjacent epidermis and to 5 cases of sporadic KA used as controls.
      CONCLUSION: This observation indicates that a solitary SKA may be the first
      clinical manifestation of MTS and brings up the relevance for regular
      dermatological screening for MTS-associated skin lesions among gene carriers (and
      symptomatic individuals) for HNPCC syndrome.

PMID- 19602867
TI  - Catamenial hemoptysis: a nationwide analysis in Korea.
AB  - BACKGROUND: Hemoptysis is a potentially serious clinical problem. However, there
      is no consensus on the clinical characteristics, treatment and patient outcome of
      catamenial hemoptysis. OBJECTIVE: Clinical characteristics, treatments and
      outcome in patients of catamenial hemoptysis were evaluated. METHODS: We
      conducted a retrospective nationwide observational analysis of Korean patients
      with catamenial hemoptysis. RESULTS: Nineteen patients with catamenial hemoptysis
      were evaluated from 13 tertiary-care hospitals in Korea. The median age of the
      patients was 25 years; 8 (42%) were ever-smokers. Eight patients were
      pathologically diagnosed; 11 were diagnosed by clinical criteria. Sixteen (84%)
      patients had a history of obstetric or gynecological procedures before developing
      hemoptysis. The mean amount of hemoptysis (mean +/- SD) was 58.3 +/- 71.3 for
      surgery, 46.4 +/- 33.2 for hormonal and 29.1 +/- 26.3 for conservative treatment
      groups. Hemoptysis did not recur in 8 (89%) of 9 patients after surgery. None of
      the patients in the hormonal or conservative treatment groups had persistent
      hemoptysis. There was an excellent outcome (complete remission and partial
      responses) in all patients with conservative treatment, suggesting that
      endometrial cells implanted into the lung may have a benign course. CONCLUSION:
      Patients without massive hemoptysis can be treated conservatively or with
      hormonal agents.

PMID- 19602868
TI  - Degarelix: a new approach for the treatment of prostate cancer.
AB  - Androgen deprivation therapy remains the mainstay of medical treatment for
      prostate cancer. Generally, this is achieved with medical androgen deprivation
      rather than orchidectomy, as most patients find the permanency and psychological
      effects of the latter unacceptable. Gonadotrophin-releasing hormone (GnRH)
      agonists are the most widely used androgen deprivation therapy, but do have some
      drawbacks. The most apparent is the induction of a transient surge in serum
      testosterone that may stimulate tumor growth, causing patients to experience new
      or worsening cancer symptoms. These may include increased bone pain and urinary
      retention, and consequently delay the therapeutic benefit of these agents. These
      shortcomings led to the development of the GnRH antagonists/receptor blockers.
      Degarelix is a novel GnRH receptor blocker that has an immediate onset of action,
      producing a rapid decrease in luteinizing hormone and follicle-stimulating
      hormone leading to fast testosterone suppression without the initial surge
      associated with the GnRH agonists. Administration of subcutaneous degarelix depot
      has been investigated in multicenter, open-label, randomized, phase II trials of
      up to 1 year's duration in patients with prostate cancer. Degarelix induced rapid
      luteinizing hormone suppression and fast, profound and sustained suppression of
      serum testosterone (<or=0.5 ng/ml), with additional rapid and sustained
      reductions in dihydrotestosterone and prostate-specific antigen. Dose-finding
      trials indicate that a 240 mg starting dose and an 80 or 160 mg maintenance dose
      is most effective for long-term testosterone suppression. In a phase III, 1-year
      comparator trial, degarelix produced fast testosterone suppression and prostate
      specific antigen reduction >or=2 weeks before clinically relevant changes were
      induced by the GnRH agonist leuprolide. Degarelix was as effective as leuprolide
      at reducing testosterone <or=0.5 ng/ml from 1 month to study end. Degarelix was
      well tolerated, with uneventful toxicology and no evidence of systemic allergic
      reactions. This new agent represents an important pharmacological development in
      the hormonal treatment of prostate cancer.

PMID- 19602869
TI  - Phosphorylated cyclic-AMP-response element-binding protein and thyroid hormone
      receptor have independent response elements in the rat thyrotropin-releasing
      hormone promoter: an analysis in hypothalamic cells.
AB  - BACKGROUND: Thyrotropin-releasing hormone (TRH) from the hypothalamic
      paraventricular nucleus (PVN) controls the activity of the hypothalamus-pituitary
      thyroid axis. TRH is expressed in other hypothalamic nuclei but is downregulated
      by 3,3',5-L-triiodothyronine (T(3)) exclusively in the PVN. Thyroid hormone
      receptors (TRs) bind TRH promoter at Site-4 (-59/-52), also proposed to bind
      phosphorylated cAMP response element-binding protein (pCREB). However, nuclear
      extracts from 8Br-cAMP-stimulated hypothalamic cells showed no binding to Site-4
      and instead to cAMP response element (CRE)-2 (-101/-94). METHODS: We
      characterized, by DNA footprinting and chromatin immunoprecipitation, the sites
      in the rat (-242/+34) TRH promoter that bind to nuclear factors of hypothalamic
      primary cultures incubated with 8Br-cAMP and/or T(3). RESULTS: In primary
      cultures of fetal hypothalamic cells, TRH mRNA levels rapidly diminished with 10
      nM T(3) while they increased by 1 mM 8Br-cAMP (+/- T(3)). Site-4 was protected
      from DNase I digestion with nuclear extracts from T(3)-incubated cells but not
      from controls or from those incubated with 8Br-cAMP, which protected CRE-2; T(3)
      + 8Br-cAMP coincubation caused no interference. The region protected by nuclear
      extracts from cAMP-stimulated cells included sequences adjacent to CRE-2
      containing response elements of the SP/Kruppel family. A TRbeta2 antibody
      immunoprecipitated chromatin containing Site-4 but not CRE-2, from cells
      incubated with T(3). A pCREB antibody immunoprecipitated CRE-2 containing
      chromatin in controls and more in 8Br-cAMP-stimulated cells but none when cells
      were incubated only with T(3). Recruitment of the 2 transcription factors was
      preserved in cells simultaneously exposed to 8Br-cAMP and T(3). DISCUSSION: These
      results show that pCREB binds to a response element in the TRH promoter (CRE-2)
      that is independent of Site-4 where TRbeta2 is bound; pCREB and TR do not present
      mutual interference on their binding sites.

PMID- 19602871
TI  - Patients' satisfaction with flexible bronchoscopy in a hospital-based community
      practice.
AB  - BACKGROUND: There are no data about patients' satisfaction with a first
      bronchoscopy in community practice. OBJECTIVES: The aim of this study was to
      assess the satisfaction with flexible bronchoscopy and the willingness to return
      for the procedure if needed in hospital-based community practice. METHODS:
      Prospective administration of a questionnaire before and after flexible
      bronchoscopy with inclusion of 126 patients in the analysis. RESULTS: The
      reliability analysis demonstrated a good internal consistency of the
      questionnaire with a mean Cronbach alpha of 0.7 (range 0.63-0.76). Health status
      and overall satisfaction with bronchoscopy were reported as poor by 31 (25%) and
      0 (0%) patients, fair by 34 (27%) and 3 (2%) patients, good by 47 (37%) and 51
      (40%) patients and very good by 9 (7%) and 70 (56%) patients, respectively.
      Overall willingness to return for a flexible bronchoscopy if necessary was 98%
      (123/126). Transbronchial needle aspiration (TBNA) was the most often performed
      diagnostic procedure (74/126, 59%). Mean duration of the bronchoscopy in patients
      with and without TBNA was 30 and 19 min, respectively (p < 0.001). However, TBNA
      did not influence patient's satisfaction. Preprocedure anxiety was reported by 26
      of 51 patients (51%) and 24 of these patients (92%) rated their anxiety as
      unjustified after the procedure. CONCLUSIONS: Overall satisfaction and
      willingness to return for a flexible bronchoscopy in community practice are
      extremely high and these are independent of whether TBNA is undertaken or not.

PMID- 19602870
TI  - The association of nocturnal hypoxemia with arterial stiffness and endothelial
      dysfunction in male patients with obstructive sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with
      cardiovascular complications, and atherosclerosis is considered to mediate this
      association. Arterial stiffness and endothelial dysfunction are widely accepted
      as early markers of atherosclerosis. OBJECTIVES: The purpose of this study was to
      investigate the influence of sleep apnea on arterial stiffness and endothelial
      dysfunction. METHODS: We enrolled 83 OSAS patients including 39 with mild to
      moderate degree (apnea hypopnea index, AHI >or=5, AHI <30) and 44 with severe
      degree sleep apnea (AHI >or=30) and 29 normal control subjects (AHI <5). After
      finishing polysomnography, carotid-femoral pulse wave velocity (cfPWV) and flow
      mediated dilation (FMD) were measured using noninvasive devices. RESULTS: In
      patients with severe degree of OSAS, cfPWV was significantly higher than mild to
      moderate degree of OSAS or normal control subjects. Also, the severe OSAS group
      showed lower FMD than the normal control group (all p < 0.01). The cfPWV was
      significantly correlated with FMD (r = -0.26, p < 0.01). Age (beta = 0.33, p <
      0.01) and percentage of time below 90% O(2) saturation (beta = 0.34, p < 0.01)
      were the significant variables to determine cfPWV (adjusted R(2) = 21%, p < 0.01)
      in multivariate analysis, and the lowest O(2) saturation was a significant
      determinant for FMD (beta = 0.25, adjusted R(2) = 6%, p < 0.01). CONCLUSIONS:
      Nocturnal hypoxemia may alter arterial elasticity and endothelial function in
      OSAS patients, and those impairments could increase the risk of cardiovascular
      complications.

PMID- 19602872
TI  - Which dry powder inhaler should be chosen?

PMID- 19602873
TI  - Functional abilities in older adults with mild cognitive impairment.
AB  - BACKGROUND: A classification scheme and general set of criteria for diagnosing
      mild cognitive impairment (MCI) were recently proposed by a multidisciplinary
      group of experts who met at an international symposium on MCI. One of the
      proposed criteria included preserved basic activities of daily living and minimal
      impairment in complex instrumental activities of daily living (IADLs). OBJECTIVE:
      To investigate whether older adults with MCI classified according to the subtypes
      identified by the Working Group (i.e. amnestic, single non-memory domain, and
      multiple domain with or without a memory component) differed from cognitively
      intact older adults on a variety of measures indexing IADLs and to examine how
      well measures of IADL predict concurrent MCI status. METHODS: Two hundred and
      fifty community-dwelling older adults, ranging in age from 66 to 92, completed
      self-report measures of IADLs (Lawton and Brody IADL Scale, Scales of Independent
      Behaviour-Revised--SIB-R) and a measure of everyday problem solving indexing
      IADLs (Everyday Problems Test--EPT). Ratings of participants' IADL functioning
      were also obtained from informants (e.g. spouse, adult child and friend).
      RESULTS: Older adults with multiple-domain MCI demonstrated poorer IADL
      functioning than older adults with no cognitive impairment on the EPT and the SIB
      R (both self- and informant-report versions). The multiple-domain MCI
      participants also demonstrated poorer IADLs than MCI participants with
      impairments in a single cognitive domain on the self-reported SIB-R and EPT. The
      single-domain MCI groups demonstrated poorer IADLs than older adults without
      cognitive impairment on the informant-reported SIB-R and EPT. No significant
      group differences were found on the Lawton and Brody IADL Scale. Using the EPT
      and SIB-R as predictors in a multinomial regression analysis, MCI group status
      was reliably predicted, but the classification rate was poor. CONCLUSION:
      Individuals with MCI demonstrated poorer IADL functioning compared to cognitively
      intact older adults. However, the changes in IADL functioning observed in MCI may
      be too subtle to be detected by certain measures, such as the Lawton and Brody
      IADL Scale.

PMID- 19602874
TI  - Second-generation tyrosine kinase inhibitors in the post-transplant period in
      patients with chronic myeloid leukemia or Philadelphia-positive acute
      lymphoblastic leukemia.

PMID- 19602875
TI  - Suggestions for reviewing manuscripts.
AB  - BACKGROUND: Scientific reviewing is a voluntary process to determine if a
      manuscript deserves publication. REVIEW MEANS: Responsibly Evaluate, Verify and
      Improve the manuscript, Educate the authors and editors, and Weigh your expert
      opinion against the submitted work. Provide your review in a respectful, unbiased
      and timely manner. REVIEW METHODS: Make sure editors know about your willingness
      to review and your particular area(s) of expertise. If you find yourself in a
      conflict of interest, decline to participate in reviewing. If you accept,
      complete reviews on time. Determine and rate (1) the methodological validity, (2)
      originality, (3) significance of findings, (4) the style and clarity of
      presentation and (5) the findings' interest to the readership of the journal for
      which you are asked to review a manuscript. Specifically evaluate (6) if the
      results support any claims or conclusions made and, most importantly, (7) if the
      abstract correctly reflects the full content of a manuscript. Summarize your
      review in specific comments to the authors. Make recommendations whether to
      accept, revise or reject the manuscript to the editor only. REVIEW RESULTS: Start
      with a brief summary of the manuscript's subject, strengths and key
      findings/claims. Present your specific criticisms and suggestions in numbered
      lists for the authors to address. Never use demeaning and offensive words or
      sarcasm since, in the first place, this reflects upon your own ethics and
      integrity as well as upon the journal's. Use a constructive tone, and if you see
      any deficiencies, educate the authors in a respectful manner so that, even if a
      manuscript is rejected, they will learn from you, improve the manuscript or
      conduct a better study in the future. Also include ratings from 1 to 7 in your
      comments to the authors, as far as they are relevant and may explain your final
      decision. CONCLUSIONS: Judge others as you would like to be judged yourself. We
      hope these suggestions serve to help new reviewers and refresh the willingness of
      battle-hardened veterans to continuously serve the medical literature.

PMID- 19602876
TI  - Clinical significance of posterior circulation changes after revascularization in
      patients with moyamoya disease.
AB  - OBJECTIVE: It has been noted that the posterior circulation serves as an
      important source of collateral blood supply in moyamoya disease. Since most of
      the literature has focused on non-operative cases and many symptomatic patients
      receive surgical revascularization, we evaluated the posterior circulation
      changes after revascularization and found that progressive posterior cerebral
      artery (PCA) steno-occlusive changes after revascularization caused cerebral
      hemodynamic compromise and clinical deterioration in a significant portion of
      patients. METHODS: Twenty-three moyamoya disease patients with ischemic
      presentation who received revascularization with complete angiography and xenon
      CT during a minimum of 3 years' clinical follow-up were enrolled.
      Revascularization was performed in 38 hemispheres. Pre- and postoperative
      angiography were reviewed to determine the internal carotid artery (ICA) stage,
      PCA stage, leptomeningeal collateral (LMC) grade, and Matsushima synangiosis
      grade. The postoperative regional cerebral blood flow (CBF) and cerebral vascular
      reserve (CVR) were recorded and correlated with angiographic findings and
      clinical outcome. RESULTS: Progression of ICA staging was noted in 23 sides
      (55.2%), and progression of PCA staging was noted in 18 sides (47.4%). Among the
      18 cases of PCA stage progression, an associated decrease in LMC grade was noted
      in 12 sides (66.7%). These changes were associated with decreased regional CBF
      and CVR, which also explained the recurrent ischemic symptoms in 27.8% of these
      patients. In contrast, LMC grade increased in 15 (65.2%) sides of patients with
      ICA progression. CONCLUSIONS: Progressive steno-occlusive change in the PCA after
      revascularization is associated with a reduction in LMC blood flow and cerebral
      ischemia in moyamoya patients. This phenomenon might cause recurrent ischemic
      symptoms in 27.8% of patients.

PMID- 19602877
TI  - Moyamoya disease: collateralization is everything.

PMID- 19602878
TI  - Early outcome of combined thrombolysis based on the mismatch on perfusion CT.
AB  - BACKGROUND: Possible factors associated with early outcome after thrombolysis are
      the recanalization time and the status of tissue. We assessed whether combined
      intravenous (IV) and intra-arterial (IA) thrombolysis performed according to the
      status of tissue based on perfusion computed tomography (PCT) is beneficial for
      the early outcome in patients with acute ischemic stroke. METHODS: To improve the
      recanalization time, we assumed that combined IA thrombolysis after IV
      thrombolysis would be beneficial. Eligible patients for combined thrombolysis
      were selected according to the status of tissue based on PCT. Recanalization was
      defined as Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3. 'Good
      functional outcome' was defined as a Modified Rankin Scale (mRS) score of 2 or
      less at discharge. RESULTS: Eighteen patients (11 men) underwent combined IV/IA
      thrombolysis. The recanalization rate after combined IV/IA thrombolysis was 88.9%
      (TIMI 2, 4; TIMI 3, 12). A good functional outcome at discharge was noted in 12
      patients (66.7%). The incidence of symptomatic intracranial hemorrhage was 5.6%
      (1/18). CONCLUSIONS: The results of this study suggest that combined IV/IA
      thrombolysis based on the presence of mismatches on PCT might have a relatively
      high rate of recanalization and a favorable early outcome. In addition, the
      incidence of symptomatic intracranial hemorrhage was acceptable.

PMID- 19602879
TI  - Enhanced activity of inositol-1,4,5-trisphosphate receptors in atrial myocytes of
      atrial fibrillation patients.
AB  - The roles of inositol-1,4,5-trisphosphate receptors (IP3Rs) in arrhythmia are not
      fully understood, especially in human beings. Recently, the reported upregulated
      expression of IP3Rs in atrial myocytes of atrial fibrillation (AF) subjects
      suggested that IP3Rs might be associated with AF. To directly understand the
      roles of IP3Rs in AF, we have investigated the IP3R-dependent Ca2+ events as well
      as the cross-talk between IP3Rs and ryanodine receptors (RyRs) in permeabilized
      atrial myocytes of AF and normal sinus rhythm (NSR) patients by Ca2+ imaging. In
      the presence of tetracaine, IP(3)R-dependent Ca2+ events in AF atrial myocytes
      showed increased frequency, delayed termination and broadened width, compared
      with NSR myocytes. Moreover, when RyRs were not inhibited, IP3 or adenophostin
      induced an outburst of RyR-dependent spontaneous Ca2+ sparks with the altered
      spatial-temporal characteristics. The activation of IP3Rs also enhanced Ca2+
      waves. These effects on RyR-dependent Ca2+ signaling were significantly stronger
      in AF myocytes than in NSR cells and were completely blocked by 2
      aminoethoxydiphenyl borate. Thus, our results suggested not only an enhanced
      activity of IP3Rs but also an elevated cross-talk between IP3R- and RyR-mediated
      Ca2+ signaling in atrial myocytes of human AF patients, a reflection of altered
      function of IP3Rs in AF.

PMID- 19602881
TI  - Arrhythmia susceptibility in mice after therapy with beta-catenin-transduced
      hematopoietic progenitor cells after myocardial ischemia/reperfusion.
AB  - BACKGROUND: Hematopoietic progenitor cells (HPCs) can improve cardiac function
      after myocardial infarction. However, occurrence of arrhythmias is a potential
      limitation of cell therapy. In this study, we investigated the cardiac
      electrophysiological properties of ex vivo expanded HPCs, generated by beta
      catenin gene transfer, after transcoronary delivery in a murine model of
      ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: To assess arrhythmia
      inducibility of ex vivo expanded HPCs, mice were subjected to I/R and assigned to
      sham operation (n = 8), I/R (n = 21) and HPC (n = 15) treatment. Six weeks later,
      mice were subjected to long-term electrocardiogram recording and in vivo
      transvenous electrophysiological study. After I/R, mice showed a significant
      prolongation of conduction and repolarization compared with sham-operated mice.
      There was a marked increase in ventricular ectopic activity in infarcted mice as
      compared with sham-operated mice. Cardiac electrophysiological parameters and
      ventricular ectopic activity were not altered in mice treated with HPCs in
      comparison with control I/R mice. CONCLUSION: Transcoronary delivery of
      genetically ex vivoexpanded HPCs did not alter the electrophysiological
      properties in mice after I/R. Therefore, ex vivo beta-catenin-mediated HPC
      expansion may represent an attractive therapeutic option for cell transplantation
      treatment of myocardial infarction without electrophysiological side effects.

PMID- 19602880
TI  - Flushing profile of extended-release niacin/laropiprant at initiation of therapy
      in Asian lipid clinic patients.
AB  - OBJECTIVE: Niacin is underutilized due to flushing, which occurs in over 90% of
      niacin-treated patients. Laropiprant (LRPT) reduces flushing associated with
      niacin. This study compared flushing with a combination tablet of extended
      release (ER) niacin (ERN)/LRPT to niacin ER (N-ER; without LRPT) during the first
      week of therapy among patients in Asia. METHODS: Following a 1-week placebo run
      in, 332 patients with dyslipidemia from China, Korea and Singapore were
      randomized to ERN/LRPT 1 g/20 mg, N-ER 1 g (given as Niaspan(R)) or placebo in a
      2:2:1 ratio for 1 week. Patient-reported flushing severity was assessed using the
      Global Flushing Severity Score (GFSS; none/mild = 0-3; moderate = 4-6; severe = 7
      9; extreme = 10). RESULTS: Compared with N-ER, the ERN/LRPT group experienced
      significantly less flushing (p < 0.001), as measured by maximum GFSS categorized
      as none/mild, moderate, severe or extreme. Overall, 23.8% of patients in the
      ERN/LRPT group and 50.0% in the N-ER group (p < 0.001), versus 12.1% in the
      placebo group, had moderate or greater flushing (GFSS > or =4). Except for
      flushing, which occurred more frequently in the N-ER group, ERN/LRPT had a
      safety/tolerability profile similar to that of N-ER. CONCLUSION: ERN/LRPT
      produced significantly less flushing than N-ER during the initiation of therapy
      and was generally well tolerated in Asian patients with dyslipidemia.

PMID- 19602882
TI  - Infective endocarditis by Bartonella quintana masquerading as antineutrophil
      cytoplasmic antibody-associated small vessel vasculitis.
AB  - The Bartonella species have been recently recognized as important causative
      agents of culture-negative bacterial endocarditis. Antineutrophil cytoplasmic
      antibodies (ANCAs) have been associated with the spectrum of idiopathic small
      vessel vasculitis. However, a variety of infections can result in a false
      positive ANCA test, and especially subacute bacterial endocarditis (SBE) with the
      presence of ANCAs occasionally mimics the clinical manifestations of an ANCA
      associated vasculitis such as skin purpura and glomerulonephritis. In contrast,
      noninfectious endocardial involvement is known to be part of the spectrum of the
      manifestations of the ANCA-associated vasculitis. Therefore, it is crucial to
      distinguish an ANCA-positive SBE from an ANCA-associated vasculitis with
      endocardial compromise, because the misdiagnosis of an SBE as an ANCA-associated
      vasculitis can lead to an inappropriate immunosuppressive therapy with
      catastrophic consequences. The differential diagnosis is sometimes difficult,
      especially in the case of culture-negative infective endocarditis with a positive
      ANCA test. We describe here a case of a culture-negative SBE caused by
      Bartonellaquintana, accompanied with a positive cytoplasmic ANCA test and
      clinical findings masquerading as ANCA-associated vasculitis. Both a serological
      test for Bartonella and polymerase chain reaction restriction fragment length
      polymorphism analysis were helpful for a correct diagnosis and appropriate
      treatment.

PMID- 19602883
TI  - Increased risk for falling associated with subtle cognitive impairment: secondary
      analysis of a randomized clinical trial.
AB  - BACKGROUND/AIMS: Having dementia increases patients' risk for accidental falls.
      However, it is unknown if having mild cognitive deficits also elevates a person's
      risk for falls. This study sought to clarify the relationship between subtle
      cognitive impairment, measured with a widely-used, clinic-based assessment, the
      Mini Mental State Exam (MMSE), and risk for falls. METHODS: In a secondary
      analysis of the Kenosha County Falls Prevention Study, a randomized controlled
      trial targeting older adults at risk for falls, we examined the association
      between baseline MMSE and prospective rate of falls over 12 months in 172
      subjects randomized to control group. RESULTS: Using univariate analysis, the
      rate of falls increased with each unit decrease in MMSE score down to at least 22
      (rate ratio 1.25, 95% confidence interval (CI) 1.09-1.45, p = 0.0026). Using
      stepwise multivariate regression, controlling for ability to perform activities
      of daily living, use of assistive device, current exercise, and arthritis, the
      association between MMSE score and falls rate persisted (rate ratio 1.20, 95% CI
      1.03-1.40, p = 0.021). CONCLUSION: Minimal decrements on the MMSE were associated
      with elevations in rate of falls, suggesting that subtle cognitive deficits
      reflected in MMSE scores above a cut-off consistent with a diagnosis of dementia,
      can influence risk for falls.

PMID- 19602884
TI  - Cognitive and noncognitive neurological features of young-onset dementia.
AB  - BACKGROUND: The rarity of young-onset dementia (YOD), the broad differential
      diagnosis and unusual clinical presentations present unique challenges to
      correctly recognize the condition and establish an accurate diagnosis. Limited
      data exist regarding clinical features associated with dementia prior to the age
      of 45. METHODS: We retrospectively assessed cognitive and noncognitive
      neurological characteristics of 235 patients who presented for evaluation of YOD
      to investigate the clinical characteristics of YOD compared to later-onset
      dementias and to identify clinical features associated with specific etiologies
      that may aid in the evaluation of YOD. RESULTS: Multiple cognitive domains were
      affected in most patients, and no significant differences in affected domains
      existed between groups. Early psychiatric and behavioral features occurred at
      very high frequencies. Nearly 80% of this YOD cohort had additional noncognitive
      symptoms or signs as a feature of their disease. Chorea was strongly associated
      with Huntington disease. Parkinsonism was not seen in patients having an
      autoimmune/inflammatory etiology. CONCLUSIONS: The rarity of YOD and the high
      frequency of early psychiatric features led to frequent misdiagnosis early in the
      clinical course. The high frequency of noncognitive symptoms and signs may aid
      clinicians in distinguishing patients requiring a more extensive evaluation for
      YOD.

PMID- 19602885
TI  - Spanish version of the Bayer Activities of Daily Living scale in mild cognitive
      impairment and mild Alzheimer disease: discriminant and concurrent validity.
AB  - AIMS: To test the discriminant and concurrent validity of the Spanish version of
      the Bayer Activities of Daily Living scale (B-ADL) in mild cognitive impairment
      (MCI) and mild Alzheimer disease (AD). METHODS: The B-ADL scale, the Blessed
      Dementia Rating Scale (BDRS), and the Interview for Deterioration in Daily Living
      in Dementia (IDDD) were administered to 277 elderly Spanish patients (78 MCI and
      199 AD). Correlations between scales were performed, and ROC curves were plotted.
      RESULTS: In MCI and mild AD discrimination, an area under the ROC curve of 0.84
      was found; a cut-off point of 3.3 was proposed with values of 0.81 for
      sensitivity and 0.72 for specificity. The B-ADL correlated positively to both the
      BDRS (r = 0.7) and the IDDD (r = 0.8). CONCLUSION: The B-ADL is a valid and
      sensitive scale that can be used to discriminate mild AD from MCI.

PMID- 19602886
TI  - Association between plasma homocysteine levels and mortality in elderly patients
      with mental illness.
AB  - BACKGROUND/METHOD: Total plasma homocysteine (tHcy) concentration is elevated in
      elderly patients with mental illness. Plasma tHcy is known to be associated with
      cardiovascular disease, renal impairment and negative lifestyle factors, and has
      been shown to predict mortality in human subjects. Epidemiological data on this
      topic in elderly patients with mental illness are missing. We therefore
      investigated the association between plasma tHcy levels and mortality in these
      patients. RESULTS: The group of deceased patients showed higher age, higher
      plasma tHcy, lower renal function and lower serum folate than patients who were
      still alive. Only age, plasma tHcy and the presence of vascular disease
      significantly influenced mortality. CONCLUSION: The association between plasma
      tHcy level and mortality risk was probably explained in part by the two plasma
      tHcy determinants age and presence of vascular disease. The determination of
      plasma tHcy in elderly patients with mental illness may help to identify patients
      in need of more intensive treatment.

PMID- 19602887
TI  - Evaluation of cerebellar asymmetry in Alzheimer's disease: a stereological study.
AB  - OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia and, as
      previous studies have indicated, degenerative changes in the cerebellum occur in
      AD. It is well known that the cerebellum does not have a symmetric morphology and
      some pathological disorders, such as schizophrenia, epilepsy, autism and
      alcoholism, can cause asymmetrical changes in the cerebellum. In this study, we
      aimed to evaluate whether or not patients with AD show cerebellar asymmetry. We
      also intended to depict the probable volumetric asymmetry by using a
      stereological technique. MATERIALS AND METHODS: The study evaluated the
      volumetric measurements of each cerebellar hemisphere by applying a stereological
      method to MR images. This age- and gender-matched study was composed of 15
      patients with probable AD and 14 healthy subjects (controls). MR images were
      analyzed by using the point-counting approach, holding to Cavalieri's principle.
      RESULTS: Although there was significant cerebellar atrophy in AD patients, the
      study showed no statistically significant cerebellar asymmetry according to age
      and gender, both in the study and control groups (p > 0.05). CONCLUSIONS: There
      was no difference in cerebellar asymmetry associated with age and gender between
      the AD patients and control subjects. The stereological evaluation of cerebellar
      asymmetry correlating with gender is of importance to both clinicians and
      anatomists. The technique is simple, inexpensive, reliable and unbiased.

PMID- 19602889
TI  - Risk factors for post-pancreaticoduodenectomy bleeding and finding an innovative
      approach to treatment.
AB  - BACKGROUND: This study is to determine the risk factors and outcome for post
      pancreaticoduodenectomy bleeding, and to assess the roles of surgery and
      intravascular intervention in its management. METHODS: Post
      pancreaticoduodenectomy data of 628 patients were analyzed with regards to post
      pancreaticoduodenectomy bleeding. RESULTS: Post-pancreaticoduodenectomy bleeding
      occurred in 58 patients (9.2%) and led to death in 23 patients. Pancreatic
      leakage and intra-abdominal abscess were independent risk factors for both
      extraluminal and intraluminal post-pancreaticoduodenectomy bleeding. The most
      common source of bleeding was the gastroduodenal artery (n = 9, 24.3%), and 8 of
      these patients (88.9%) experienced gastroduodenal artery bleeding in late post
      pancreaticoduodenectomy bleeding. Hemostasis for post-pancreaticoduodenectomy
      bleeding was achieved by surgery in 22 patients (78.6%) and intravascular
      intervention in 7 patients (58.3%). Transarterial embolization for gastroduodenal
      artery bleeding did not deteriorate liver function in most patients except for 1
      who died of hepatic failure. CONCLUSIONS: The placement of metallic clips on the
      gastroduodenal artery stump during a pancreaticoduodenectomy is helpful in
      identifying overlooked intermittent sentinel bleeding during angiography.
      Transarterial embolization for gastroduodenal artery bleeding could not guarantee
      against hepatic failure. The intravascular placement of a covered stent is the
      preferred procedure to avoid the complete interruption of arterial blood supply
      to the liver.

PMID- 19602888
TI  - Cognitive function in Japanese centenarians according to the Mini-Mental State
      Examination.
AB  - BACKGROUND/AIMS: We examined the effect of aging on cognitive function at the
      limit of human life expectancy by characterizing state of cognition in
      centenarians without clinical cognitive impairment. METHODS: Participants were 68
      centenarians without cognitive impairment (Clinical Dementia Rating (CDR) 0), 96
      controls 60 to 74 years old, and 46 controls 75 to 89 years old. We visited the
      places where centenarians were living and administered the Mini-Mental State
      Examination (MMSE) individually. Control subjects came to the assembly hall
      within their dwelling area, to be administered the MMSE. RESULTS: Mean total
      scores of centenarians (22.3) were lower than for either 60-74 (27.2) or 75-89
      (26.2). Comparison of scores in each of five cognitive domains measured by MMSE
      showed a significant age-group effect upon orientation, memory, and attention.
      Centenarians' scores were lower than for younger groups in every domain except
      for the language and praxis, concentration, and for repetition. CONCLUSION: The
      centenarians' scores in memory and orientation declined as in earlier studies of
      normal aging. Centenarians' scores for attention and concentration differed from
      those in previous studies. The present result suggests that even primary memory
      is influenced by advanced age in centenarians, while ability to store information
      declines, ability to process is maintained.

PMID- 19602890
TI  - Excessive Daytime sleepiness in idiopathic restless legs syndrome:
      characteristics and evolution under dopaminergic treatment.
AB  - BACKGROUND/AIMS: Whereas insomnia is frequent in restless legs syndrome (RLS),
      little is known about daytime sleepiness. We studied a series of 27 consecutive
      patients with idiopathic RLS in order to identify the characteristics and
      evolution of excessive daytime sleepiness (EDS) under dopaminergic treatment.
      METHODS: Patients were assessed by clinical examination, questionnaires and video
      polysomnography (PSG). Sleepy patients, as defined by Epworth Sleepiness Scale
      (ESS) >10, were also assessed by the multiple sleep latency test (MSLT). We
      excluded RLS patients with other sleep-wake disorders, in particular chronic
      sleep deprivation. RESULTS: Mean age was 56 years, the mean International RLS
      Study Group Rating Scale score was 24 at baseline. Ten (37%) of the 27 patients
      reported EDS. RLS patients with sleepiness had a higher amount of total sleep
      time (p = 0.029) on PSG and a mean sleep latency of 6.4 min on MSLT. No other
      differences regarding clinical or polysomnographic parameters were found. RLS
      severity improved in all patients under dopaminergic treatment (p = 0.001); this
      was also the case for the ESS score in sleepy patients (p = 0.007). CONCLUSION:
      In our series of RLS patients, EDS was common, characterized by longer sleep
      (PSG) and reduced sleep latencies on MSLT. Under dopaminergic treatment, both RLS
      severity and ESS improved.

PMID- 19602891
TI  - Yawning in diseases.
AB  - Yawning is a physiological behavior, an emotional stereotypy that indicates the
      homeostatic process of the mechanisms regulating rhythms, such as
      sleeping/waking, hunger/satiety or mating/relaxation, generated by the
      diencephalon. As with all physiological behaviors, its deregulation reveals
      disorders. In daily practice, yawning as a symptom is generally neglected. That
      is why we propose a wide overview of yawning in diseases, its consequences and
      significance.

PMID- 19602892
TI  - 'Les ictus amnesiques' and transient global amnesia.
AB  - In March 1909, R. Benon was probably the first to report a typical case of what
      we now call transient global amnesia. In 1956, Bender, and independently, Guyotat
      and Courjon described clinical and epidemiological features of transient amnesic
      attacks. The condition achieved general recognition after the term transient
      global amnesia (TGA) was introduced by Fisher and Adams in 1958. Their historic
      work is the main focus of this review. They reported 17 patients, with an abrupt
      anterograde amnesia of short duration. Classification and criteria are outlined.
      Various aetiologies have been postulated, but although TGA remains a clinically
      distinct syndrome, usually with a good prognosis, evidence of neither ischaemia
      nor epilepsy is demonstrable in most patients. Theories of jugular venous reflux
      may be relevant in some but probably not in most cases of this heterogeneous
      disorder.

PMID- 19602893
TI  - Crime, hysteria and belle epoque hypnotism: the path traced by Jean-Martin
      Charcot and Georges Gilles de la Tourette.
AB  - Hysteria and hypnotism became a favorite topic of studies in the fin de siecle
      neurology that emerged from the school organized at La Salpetriere by Jean-Martin
      Charcot, where he had arrived in 1861. Georges Gilles de la Tourette started
      working with Charcot in 1884 and probably remained his most faithful student,
      even after his mentor's death in 1893. This collaboration was particularly
      intense on 'criminal hypnotism', an issue on which Hippolyte Bernheim and his
      colleagues from the Nancy School challenged the positions taken by the
      Salpetriere School. Bernheim claimed that hypnotism was not a diagnostic feature
      of hysteria and that there were real-life examples of murders suggested under
      hypnosis, while hypnosis susceptibility was identified with hysteria by Charcot
      and Gilles de la Tourette, who saw rape as the only crime associated with
      hypnotism. The quarrel was particularly virulent during a series of famous
      criminal cases which took place between 1888 and 1890. At the time, it was
      considered that La Salpetriere had succeeded over Nancy, since the role of
      hypnotism was discarded during these famous trials. However, the theories of
      Charcot and Gilles de la Tourette were also damaged by the fight, which probably
      triggered the conceptual evolution leading to Joseph Babinski's revision of
      hysteria in 1901. Gilles de la Tourette's strong and public interest in hypnotism
      nearly cost him his life, when a young woman who claimed to have been hypnotized
      against her will shot him in the head at his own home in 1893. It was
      subsequently shown that hypnotism had nothing to do with it. The delusional woman
      was interned at Sainte-Anne for mental disturbance, thus escaping trial.
      Ironically, Gilles de la Tourette may have been partly responsible, since he had
      been one of the strongest proponents of placing mentally-ill criminals in asylums
      instead of prisons.

PMID- 19602894
TI  - Future screening for incipient Alzheimer's disease--the influence of prevalence
      on test performance.
AB  - Much effort has been made to identify and verify diagnostic biomarkers for early
      stage Alzheimer's disease (AD). The need for this is often advocated by possible
      future disease-modifying treatments, likely to be most effective if initiated
      early in the disease process. Since the neurodegenerative process probably starts
      many years before the first onset of symptoms, such future drugs are likely to
      invoke a need for screening presymptomatic individuals. Here, we speculate on the
      performance of currently available AD biomarkers in hypothetical screening
      programs of different designs. We note that many diagnostic tests will have an
      excellent ability to exclude upcoming AD. However, even the best tests will
      suffer from poor positive predictive values given the relatively low disease
      prevalence in populations with no or very few symptomatic individuals, also when
      taking future converters to AD into account. The magnitude of this problem, which
      is common among most screening programs, will depend on the efficacy, safety and
      cost of the future anti-AD drugs. A number of tentative solutions to the problem,
      apart from better tests, are discussed.

PMID- 19602895
TI  - Successful human vascular reconstructions with long-term refrigerated venous
      homografts.
AB  - Fresh autologous vein grafts are commonly used for infrainguinal vascular
      reconstructions with good results. Previously we have confirmed the high
      viability index of homografts even after long-term storage at 4 degrees C in
      tissue culture medium. In this clinical study, we have evaluated the in vivo
      efficiency of this storage method in humans with major peripheral graft
      infections. Between April 2006 and November 2008, data from patients who
      underwent graft excision and venous allograft reconstruction were collected
      prospectively (5 men, 2 women, mean age 68 years). Six patients had acute
      ischemia at the time of allograft reconstruction, while 3 had experienced
      anastomosis rupture. Allograft reconstruction was performed as an emergency
      procedure in 3 cases. The observed parameters included patient survival, limb
      salvage, persistence or recurrence of infection and allograft patency. In the
      follow-up period reoperation, excision or thrombectomy was necessary in 3 cases.
      There were no perioperative deaths, early amputations, persistent or recurrent
      infections. In conclusion, this study demonstrates the efficacy of long-term 4
      degrees C storage of venous allografts for revascularization in cases with
      peripheral bypass graft infection. We suggest that this technique is a useful
      option for graft preservation and propose a wide-scale introduction.

PMID- 19602896
TI  - Colonization of Gardnerella vaginalis in semen of infertile men: prevalence,
      influence on sperm characteristics, relationship with leukocyte concentration and
      clinical significance.
AB  - AIMS: To determine the prevalence of Gardnerella vaginalis in semen from
      infertile men and their negative effects on semen quality. RESULTS: Cultures were
      positive in 24/108 infertile men (22.2%) and negative in controls. Infected semen
      showed no significant difference compared with non-infected semen. On the other
      hand, infected and non-infected semen presented significant differences in
      vitality, rapid and total progressive motility, normal head and mid-piece defects
      (p < 0.01) and combined anomalies (p < 0.01 and p = 0.03, respectively) in
      comparison with the control group. Infected semen also presented significant
      differences in severely amorphous (p = 0.02) and tapered sperm (p < 0.01).
      Bacteriospermia and cells with attached bacteria (clue cells morphotype) were
      remarkable features observed. CONCLUSION: G. vaginalis in semen is not associated
      with either abnormal sperm characteristics or inflammatory response in infected
      men.

PMID- 19602897
TI  - Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic
      hepatitis C.
AB  - OBJECTIVES: We studied the status of hepatic iron deposition and its relationship
      with blood iron indices, liver histology, and HFE gene mutations in Korean
      patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who
      underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron
      deposition, histological activity and fibrosis were assessed by appropriate
      pathological scoring systems, clinical data including serum iron indices, and HFE
      gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%),
      which was not significantly associated with degree of hepatic fibrosis or
      steatosis. The serum ferritin level was elevated in 27% of the patients and was
      an independent factor associated with hepatic iron deposition by logistic
      regression; however, it was not significantly associated with hepatic fibrosis
      either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which
      was not different from the prevalence of H63D mutation in the Korean population
      (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH
      C. Neither hepatic iron deposition nor serum ferritin were significantly related
      to the severity of hepatic fibrosis, which does not support the significant role
      of iron in the progression of hepatic fibrosis.

PMID- 19602898
TI  - Predictive value of complete and partial early virological response on sustained
      virological response rates of genotype-4 chronic hepatitis C patients treated
      with PEG-interferon plus ribavirin.
AB  - OBJECTIVES: To investigate early viral kinetics, sustained virological response
      (SVR) rates and their predictors, in treatment-naive, genotype-4-infected,
      chronic hepatitis C (CHC) patients treated with PEG-IFNalpha2b plus ribavirin.
      PATIENTS AND METHODS: In total, 58 patients were retrospectively analyzed. Early
      virological response (EVR) was defined as undetectable HCV-RNA (<50 IU/ml) at
      week 12 (complete, cEVR) or at least a 2 log decrease in HCV-RNA levels (partial,
      pEVR). RESULTS: Thirty-one patients exhibited SVR (53.4%), 17 (29.3%) were non
      responders and 10 (17.2%) relapsed. Thirty-seven patients (63.8%) exhibited EVR.
      The positive predictive values of EVR, cEVR and pEVR for the SVR achievement were
      83.87, 54.83, and 29.03%, whereas their negative predictive values were 59.25,
      77.77, and 81.48%, respectively. Both cEVR (OR 0.040, p = 0.042) and EVR (OR
      0.016, p = 0.006) independently predicted SVR. Baseline viral load (p < 0.001),
      age (p = 0.035) and stage of liver disease (p = 0.04) were significantly related
      to the EVR achievement, whereas only baseline viral load (p = 0.003) and
      ethnicity (p = 0.025) predicted cEVR. CONCLUSIONS: Partial or complete EVR
      represent independent predictors of SVR in genotype-4-infected CHC patients,
      regardless of their baseline parameters. The absence of pEVR, rather than the
      absence of cEVR, should be used as an early indication for discontinuation of
      treatment in these patients.

PMID- 19602899
TI  - Discordance in human paraoxonase-1 gene between phenotypes and genotypes in
      chronic kidney disease.
AB  - BACKGROUND: Human serum paraoxonase-1 (PON1) is a high-density lipoprotein
      associated ester hydrolase which can inhibit low-density lipoprotein oxidation
      and has an antiatherogenic effect. Two common polymorphisms are known in the PON1
      gene in humans (at positions 55 and 192), from which the latter gene alteration
      has been mainly attributed to alter the activity of the protein. Moreover,
      significantly reduced PON1 activity was found in chronic kidney disease (CKD) and
      renal transplant patients. METHODS: The aim of the present study was to
      investigate the genotype and phenotype distribution of the PON1 gene as well as
      its end product activity in patients with CKD (n = 117), in renal transplant
      recipients (n = 146) and in reference subjects (n = 1,180). RESULTS: Unexpectedly
      high discordances between phenotype and genotype assessments were observed in all
      studied groups (28.2% in the CKD, 20.55% in the transplant and 30.9% in the
      reference group). Arylesterase activity was significantly lower in the CKD group
      compared to the reference sample. There were no significant differences between
      patients and the reference group in the frequencies of polymorphisms PON1-55 and
      PON1-192. PON1 activity did not differ in patients compared to the reference
      group. CONCLUSIONS: Both PON1 phenotype and genotype determinations are necessary
      to estimate PON1 status.

PMID- 19602900
TI  - Analytical review of the evidence for renoprotection by renin-angiotensin
      aldosterone system blockade in chronic kidney disease - a call for caution.
AB  - Despite reported renoprotection with angiotensin-converting enzyme inhibitors
      (ACEIs)/angiotensin receptor blockers (ARBs), and notwithstanding their increased
      use, we continue to experience an epidemic of acute renal failure (ARF)/chronic
      kidney disease/end-stage renal disease. Consequently, concerns about iatrogenic
      renal failure have resurfaced. Different analysis of these trials revealed flaws
      such as recruitment of relatively younger patients with preserved baseline renal
      function, common utilization of lower end doses of ACEIs/ARBs, high drug
      discontinuation rates, excessive use of surrogate endpoints, inadequate reporting
      of adverse effects, and short duration studies. Again, lower 24-hour ambulatory
      blood pressure among patients in the ramipril arm of the micro-HOPE (Heart
      Outcomes Prevention Evaluation) study raises doubts of renoprotection beyond
      blood pressure lowering. The disappointing results from the ONTARGET (Ongoing
      Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study
      only compounded these doubts. We demonstrated significant renal salvage after
      ACEI/ARB was discontinued in chronic kidney disease patients recruited with
      increasing ARF while on ACEI/ARB. Apart from our reports, there are increasing
      reports incriminating the use of ACEI/ARB with ARF exacerbations. We conclude
      that close and indefinite monitoring of estimated glomerular filtration rate is
      an absolute must in these patients. The treating physician must be ready to
      consider trial discontinuation of ACEI/ARB, promptly. Combination ACEI + ARB
      therapy should be the exception, rather than the rule. Temporary withdrawal of
      ACEI/ARB before certain exposures, 'renoprevention', would only further improve
      the results of renoprotection.

PMID- 19602901
TI  - Cutaneous microcirculation is impaired in early autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND/AIMS: An endothelial dysfunction has been described in autosomal
      dominant polycystic kidney disease (ADPKD) before the development of hypertension
      and renal impairment. The aim of this work was to verify the existence of a
      microvascular reactivity in the early stages of ADPKD. METHODS: Fifteen ADPKD
      normotensive patients with normal renal function underwent laser Doppler
      examination of the cutaneous microcirculation in basal conditions and after the
      warm test, as well as evaluation of plasma concentrations of some endothelial
      activation parameters [total cholesterol and fractions, fibrinogen, von
      Willebrand factor, Lp(a)]. The results were compared with those in 15 healthy
      subjects, 15 essential hypertensive patients and 15 hypertensive ADPKD patients
      with normal renal function. RESULTS: Both basal and post-warm-test values were
      significantly lower in normotensive ADPKD subjects than controls (3.2 +/- 1 vs.
      5.8 +/- 1.3 AU, p = 0.0001; 35.2 +/- 10.9 vs. 50.5 +/- 10.8 AU, p = 0.005,
      respectively). All evaluated parameters were within normal limits and comparable
      between normotensive ADPKD subjects and controls, except for LDL cholesterol (125
      +/- 18 vs. 101 +/- 22 mg/dl, p = 0.01) and Lp(a), which was significantly higher
      in the ADPKD subjects (52.2 +/- 36 vs. 6.0 +/-4 mg/dl, p = 0.0006). CONCLUSION:
      Our study confirms the existence of a systemic microcirculation defect in ADPKD.
      The presence of high levels of Lp(a) could contribute to causing the high
      incidence of cardiovascular events in ADPKD.

PMID- 19602902
TI  - Long-term favorable results by arteriovenous graft with Omniflow II prosthesis
      for hemodialysis.
AB  - AIMS AND METHODS: In order to decrease arteriovenous graft (AVG) failure and
      improve long-term patency, we used Omniflow II to perform AVG for hemodialysis
      access in 38 patients with very compromised vessels who were not suitable for
      other forms of AVG. RESULTS: At a median follow-up of 38 (range 6-55) months,
      31/38 (81%) patients were still alive. At 6, 12, 18 and 24 months, the primary
      patency was 83, 80, 68 and 60%, whereas the secondary patency was 92, 83, 78 and
      75%,respectively [corrected].The cumulative 38-month prosthetic AVG patency was
      70%. No infective event related to the vascular prosthesis occurred. Neither AVG
      thrombosis nor modifications in thrombophilic pattern were observed; these
      findings confirm the high hemocompatibility of this prosthetic vascular device.
      CONCLUSION: Our experience is extremely encouraging for the use of new
      biosynthetic devices such as Omniflow II.

PMID- 19602903
TI  - Increased aortic wall stiffness associated with low circulating fetuin A and high
      C-reactive protein in predialysis patients.
AB  - BACKGROUND/AIMS: Vascular calcification and arterial stiffening are
      cardiovascular risk factors among chronic kidney disease (CKD) patients. The aim
      of the study was to analyze relationships between inflammatory markers, fetuin A
      and arterial wall stiffness in CKD patients in the predialysis period and on
      maintenance dialysis. METHODS: Serum C-reactive protein (hs-CRP), fetuin A,
      interleukin 6 (IL-6) and other classical markers of atherosclerosis were measured
      in a group of 155 CKD patients (77 on hemodialysis, HD, 29 on peritoneal
      dialysis, 49 in CKD stage 5 in the predialysis period) and in 30 healthy
      volunteers. The aortic pulse wave velocity (aoPWV) was recorded using a
      tonometric method. RESULTS: The aoPWV, serum hs-CRP and IL-6 were higher and
      fetuin A levels were lower in all CKD groups than in controls. In multiple
      regression analysis, the age appeared as the strongest, independent factor
      increasing arterial wall stiffness in all investigated groups, including
      controls, whereas the association of aoPWV with IL-6 and fetuin A remained
      significant only in HD patients. CONCLUSIONS: Aortic wall stiffness is higher in
      CKD patients than in controls, and it already develops in the predialysis period.
      Age is the principal determinant of arterial wall stiffness also in CKD patients.
      The acceleration of arterial wall stiffness in CKD is associated with additional
      factors, i.e. fetuin A deficiency and higher CRP and IL-6.

PMID- 19602904
TI  - Fibrogenic growth factors in encapsulating peritoneal sclerosis.
AB  - BACKGROUND: Increased local levels of fibrogenic growth hormones contribute
      substantially to the process of encapsulating peritoneal sclerosis (EPS) in
      animal models. METHODS: We analyzed probes from patients with normal kidney
      function (n = 10), with normal kidney function and inflammation (n = 10), on PD
      without (n = 10) and with EPS (n = 9). We investigated the degree of fibrosis and
      the number of vessels and vasculopathy. Additionally, we investigated the
      expression of NFkappaB, TGFbeta1, TGFbeta1 receptor, TGFbeta2, TGFbeta2 receptor,
      FGF-BP, CTGF and VEGF by immunohistochemistry. RESULTS: In EPS, we found an
      exclusive upregulation of VEGF (normal 0, appendicitis 1.0 +/- 1.2, PD 1.7 +/-
      1.8 and EPS 5.7 +/- 4.4; p < 0.0001), whereas in PD, CTGF was significantly
      increased (normal 6.0 +/- 2.8, appendicitis 7.3 +/- 2.5, PD 10.0 +/- 1.8 and EPS
      7.3 +/- 2.1; p = 0.0059). The results for the TGFbeta system and NFkappaB were
      not uniform, in EPS no increases were demonstrable. Vasculopathy was
      significantly more pronounced in EPS (normal 0.4 +/- 0.5, appendicitis 0.2 +/-
      0.3, PD 1.0 +/- 0.7 and EPS 1.6 +/- 1.2; p < 0.0001) than in PD or inflammation
      (normal 30 +/- 16, appendicitis 82 +/- 48, PD 1,936 +/- 952 and EPS 2,613 +/-
      1,209; p < 0.0001), whereas the density of vessels were decreased (normal 125 +/-
      114, appendicitis 817 +/- 347, PD 81 +/- 57 and EPS 36 +/- 33; p < 0.0001).
      CONCLUSIONS: The process of EPS was associated with increased VEGF in the
      peritoneum. The reduced density of vessels compared with marked fibrosis could
      point to hypoxia as an inducer.

PMID- 19602905
TI  - Strict volume control and longitudinal changes in cardiac biomarker levels in
      hemodialysis patients.
AB  - BACKGROUND: Our aim was to analyze the longitudinal changes in cardiac biomarker
      levels in hemodialysis patients with high comorbidity treated in our special
      hospital unit. We hypothesize that strict volume control strategy (salt
      restricted diet, extended dialysis sessions and dry weight clinical assessment
      and reassessment in every session) could prevent progression of left-ventricular
      damage and, therefore, progressive increment in cardiac biomarker levels over
      time. METHODS: This is a longitudinal cohort study including 46 dialysis patients
      in which a strategy of strict volume control has been adopted. N-terminal pro-B
      type natriuretic peptide (NT-proBNP), troponin T and C-reactive protein (CRP)
      levels were measured at baseline and prospectively at 4, 8 and 12 months. The
      possible association between volume control and cardiac biomarker levels was
      analyzed. RESULTS: Dry weight could be reduced (p < 0.01) over time. A reduction
      in systolic BP (p < 0.05) and in CRP levels (p < 0.05) was observed, whereas NT
      proBNP and troponin T values remained stable. However, patients in the high
      quartile of NT-proBNP at baseline showed a reduction (p = 0.02) in troponin T
      over time with no significant trend (p = 0.08) to progressive reduction in NT
      proBNP values. CONCLUSIONS: Strict volume control in dialysis patients may
      prevent progressive increment in cardiac biomarker levels over time. The impact
      seems to be higher among patients with higher levels at baseline in whom strict
      volume control can even reduce cardiac biomarker levels on follow-up.

PMID- 19602907
TI  - Comparison of extracellular volume and blood pressure in hemodialysis and
      peritoneal dialysis patients.
AB  - BACKGROUND: Extracellular volume (ECV) assessment by bioimpedance analysis is a
      reliable technique for determining post dialysis target weight. Overhydration and
      dehydration are two points of dialysis patients' fluid status and both affect
      blood pressure. We compared ECV and blood pressure between hemodialysis and
      peritoneal dialysis patients. METHODS: We studied ECV of 74 (38 females and 36
      males) normal subjects, 121 (63 females and 58 males) stable chronic hemodialysis
      and 84 (57 females and 27 males) stable chronic peritoneal dialysis patients. ECV
      as a percentage of body weight was designated ECV%. An ECV% over 28% in male
      patients and over 25% in females was defined as overhydration according to the
      100th percentile of normal subjects. An ECV% below 21% in male patients and below
      18% in females was defined as dehydration. Hypertension was defined as systolic
      blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg. RESULTS: In male
      and female hypertension and normotension, the ECV% of peritoneal dialysis
      patients was significantly higher than that of hemodialysis patients (all p <
      0.0001). The overhydration frequency of peritoneal dialysis patients was
      significantly higher than that of hemodialysis patients (p < 0.0001). The
      dehydration frequency of peritoneal dialysis patients was significantly less than
      that of hemodialysis patients (p < 0.01). The proportion of hypertension in
      peritoneal dialysis patients was higher than that in hemodialysis patients, but
      with no significant difference (p = 0.085). All male and female patients with
      overhydration had hypertension in either the hemodialysis or peritoneal dialysis
      group. Patients with dehydration usually had normotension, but some of them had
      hypertension. CONCLUSIONS: (1) Overhydration and hypertension are more common in
      peritoneal dialysis patients than in hemodialysis patients. (2) Dehydration is
      noticed in hemodialysis patients, but not in peritoneal dialysis patients.

PMID- 19602908
TI  - How can second-line therapy for metastatic renal cell carcinoma help to define an
      overall management strategy?
AB  - For many years, therapy for metastatic renal cell carcinoma (mRCC) was limited to
      a single line of cytokine therapy with either interferon or interleukin-2.
      Relatively recently, the novel targeted agents bevacizumab, sorafenib, sunitinib
      and temsirolimus have each demonstrated activity in patients with mRCC that is
      refractory to cytokine therapy. Based on phase III trial data of patients who
      have received no prior therapy for mRCC, targeted agents have now rapidly
      replaced cytokines or, in the case of bevacizumab, are used in combination with
      interferon as first-line therapy for mRCC. Thus, second-line therapy for mRCC
      needs to be re-evaluated. Available data indicate that patients whose disease is
      refractory to a targeted agent may obtain, in some cases, benefit from a
      different agent, inhibiting either the same or a different pathway. With the
      availability of relatively few drugs for the treatment of mRCC, it is important
      to consider how to ensure that patients are obtaining maximum benefit through
      optimal use of the agents available. The definition of whether second-line
      therapy is active and tolerable and which therapy should be used in this setting
      in individual patients, particularly taking into account prior therapy, will
      therefore be important in defining the general therapeutic strategy in patients
      with mRCC.

PMID- 19602906
TI  - Genetic polymorphisms of hypoxia-inducible factor-1 alpha and cardiovascular
      disease in hemodialysis patients.
AB  - BACKGROUND: Hemodialysis patients are prone to ischemic events potentially
      aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia
      inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association
      of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis
      patients. METHODS: Patients on maintenance hemodialysis were enrolled from 4
      training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF
      1alpha were genotyped. The association of these SNP with hypoxia-related clinical
      outcomes (ischemic diseases and anemia) and cancer was analyzed. RESULTS: A total
      of 376 patients participated in the study. No significant difference in genotype
      distribution was found between subjects with and without the hypoxia-related
      events. Three sets of linkage disequilibrium blocks were made for haplotype
      analyses (rs2783778 and rs7148720 in 5' upstream region; rs7143164 and
      rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in
      the first set was associated with both acute myocardial infarction and frequent
      intradialytic hypotension (acute myocardial infarction: adjusted odds ratio =
      0.15, 95% CI: 0.03-0.69; frequent intradialytic hypotension: adjusted odds ratio
      = 0.29, 95% CI: 0.12-0.72). CONCLUSION: Genetic polymorphisms of HIF-1alpha were
      associated with acute myocardial infarction and intradialytic hypotension in
      hemodialysis patients.

PMID- 19602909
TI  - A dynamic technique for the treatment of severe or recurrent blepharoptosis:
      frontalis-orbicularis oculi muscle flap shortening.
AB  - BACKGROUND: Severe or recurrent blepharoptosis remains a great challenge to most
      plastic surgeons. A variety of techniques have been developed according to the
      function of the levator palpebrae superioris and frontalis muscles. In this
      study, the frontalis-orbicularis oculi (FOO) muscle flap is designed as an entity
      to treat severe or recurrent blepharoptosis with satisfactory results. METHODS:
      Between January 1997 and July 2007, FOO muscle flap shortening was applied to
      correct severe or recurrent blepharoptosis in 29 patients (38 eyelids), aged from
      3 to 77 years. There were 11 males and 18 females, with bilateral ptosis in 9
      patients. The follow-up period ranged from 10 to 52 months. RESULTS: Twenty-four
      patients (82%) had good results, with the degree of ptosis less than 2 mm. The
      remaining 5 patients had fair results, and received readjustment in 2 cases.
      CONCLUSION: In our study, fresh cadaver dissection revealed that the frontalis
      muscle is connected and interdigitated very closely with the orbicularis oculi
      muscle. Based on the anatomic study and literature review, we suggest that the
      FOO muscle flap shortening is a good alternative to treat severe or recurrent
      blepharoptosis.

PMID- 19602910
TI  - The effect of intravitreal ranibizumab on the fellow untreated eye with subfoveal
      scarring due to exudative age-related macular degeneration.
AB  - AIM: Our purpose was to evaluate the possible effect of intravitreal ranibizumab
      on the fellow untreated eye with choroidal neovascularization (CNV) and subfoveal
      scarring associated with age-related macular degeneration (AMD). METHODS: A
      retrospective observational study was conducted. One hundred eighty-seven
      ranibizumab-treated patients diagnosed as having subfoveal CNV scarring in the
      untreated eye were compared with a control group of untreated unilateral
      subfoveal CNV scarring. Inclusion criteria concerning treated eyes in the
      ranibizumab group complied with the MARINA and ANCHOR studies. Demographic data,
      clinical course, visual acuity, fluorescein angiography and optical coherence
      tomography findings were evaluated. RESULTS: Clinical improvement was confirmed
      in 24% of the patients in the ranibizumab group and in only 12.9% of the
      controls. Improvement was noted as early as 2-4 months (2.83 + or - 0.75 months)
      after the initiation of treatment in the fellow eye compared with 33.25 + or -
      9.43 months in the control group (p = 0.01; Mann-Whitney U test). Kaplan-Meier
      curves demonstrate the positive impact of ranibizumab on the visual acuity of the
      fellow untreated eye (p = 0.016; Log-Rank test). CONCLUSIONS: Ranibizumab might
      induce some therapeutic effect in selected cases of end-stage CNV scarring, which
      needs to be further examined. The VEGF levels in the compartments of the fellow
      eye of patients with age-related macular degeneration treated with ranibizumab
      need to be further evaluated.

PMID- 19602912
TI  - Effect of centrally administered losartan on gastric and duodenal ulcers in rats.
AB  - The effect of centrally administered losartan, an AT(1) receptor antagonist, on
      gastric acid secretion and gastric cytoprotection was studied using different
      models of gastric ulcers, such as acetic acid-induced chronic gastric ulcers,
      pylorus ligation, ethanol-induced and stress-induced acute gastric ulcers and
      cysteamine hydrochloride-induced duodenal ulcer. Losartan was administered
      intracerebroventrically (i.c.v.) at 2 different doses (125 and 250 microg/kg).
      Both doses of losartan increased the healing of acetic acid-induced chronic
      gastric ulcers. In pylorus-ligated rats, a significant reduction in free acidity,
      total acidity and ulcer index was observed with high dose (250 microg/kg,
      i.c.v.), while low dose (125 microg/kg, i.c.v.) produced reduction only in free
      acidity and ulcer index. Both doses also produced a significant antiulcer effect
      in ethanol-induced and stress-induced gastric ulcers. Losartan also reduced ulcer
      area in cysteamine-induced duodenal ulcer. We conclude that AT(1) receptor
      antagonism in the brain increases healing of gastric ulcers and reduces gastric
      acid secretion and increases gastric mucin content.

PMID- 19602911
TI  - Elevated erythropoietin in vitreous of patients with rhegmatogenous retinal
      detachment and proliferative vitreoretinopathy.
AB  - AIM: Our purpose was to determine the vitreous erythropoietin (EPO) level in
      patients with rhegmatogenous retinal detachment (RRD) and proliferative
      vitreoretinopathy (PVR). METHODS: The levels of EPO in vitreous were measured
      using a sandwich enzyme-linked immunosorbent assay kit from 64 patients, of whom
      40 had RRD, 13 had PVR and 11 had idiopathic macular hole as control. RESULTS:
      The mean levels of EPO in the RRD group (54.6 +/- 7.3 mU/ml) and PVR group (104.1
      +/- 20.8 mU/ml) were significantly higher than that in the idiopathic macular
      hole control group (14.4 +/- 3.6 mU/ml; p < 0.001, p = 0.003, respectively). The
      mean EPO level in PVR was higher than that in RRD, but the difference was not
      significant (p = 0.112). CONCLUSION: The vitreous EPO level was upregulated in
      eyes with RRD and PVR.

PMID- 19602913
TI  - Effect of mometasone furoate on nasal congestion model in rats.
AB  - AIMS: The present study was performed to evaluate the effect of mometasone
      furoate on a nasal congestion model in Brown Norway rats. METHODS: Nasal
      congestion in rats sensitized with toluene-2,4-diisocyanate (TDI) was measured
      using whole-body plethysmography which allowed animals to move freely. RESULTS:
      Penh (enhanced pause), an index of nasal congestion, was significantly increased
      after 5% TDI challenge in sensitized rats compared with that in non-sensitized
      rats. The peak of the increase in Penh appeared at 1 and 5 h after TDI challenge.
      A single topical administration of mometasone furoate (0.05%) at 1 h before TDI
      challenge suppressed the increase of Penh in sensitized rats. A significant
      effect was observed 5-6 h after nasal administration. Almost the same results
      were obtained with fluticasone propionate (0.05%). CONCLUSION: Mometasone furoate
      may therefore be effective and have a rapid onset of action in nasal congestion
      when used clinically as with fluticasone propionate.

PMID- 19602914
TI  - Cognitive-behavioral therapy, psychotherapy and psychosocial interventions in the
      medically ill.

PMID- 19602915
TI  - Short-term psychodynamic psychotherapy for somatic disorders. Systematic review
      and meta-analysis of clinical trials.
AB  - BACKGROUND: Somatic symptom disorders are common, disabling and costly.
      Individually provided short-term psychodynamic psychotherapies (STPP) have shown
      promising results. However, the effectiveness of STPP for somatic symptom
      disorders has not been reviewed. METHODS: We undertook a systematic review of
      randomized controlled trials and controlled before and after studies. The
      outcomes included psychological symptoms, physical symptoms, social-occupational
      function, healthcare utilization and treatment continuation. RESULTS: A total of
      23 studies met the inclusion criteria and covered a broad range of somatic
      disorders. Thirteen were RCTs and 10 were case series with pre-post outcome
      assessment. Of the included studies, 21/23 (91.3%), 11/12 (91.6%), 16/19 (76.2%)
      and 7/9 (77.8%) reported significant or possible effects on physical symptoms,
      psychological symptoms, social-occupational function and healthcare utilization
      respectively. Meta-analysis was possible for 14 studies and revealed significant
      effects on physical symptoms, psychiatric symptoms and social adjustment which
      were maintained in long-term follow-up. Random-effect modeling attenuated some of
      these relationships. There was a 54% greater treatment retention in the STPP
      group versus controls. CONCLUSION: STPP may be effective for a range of medical
      and physical conditions underscoring the role of patients' emotional adjustment
      in overall health. Future research should include high-quality randomized and
      clinical effectiveness studies with attention to healthcare use and costs.

PMID- 19602916
TI  - The selection and design of control conditions for randomized controlled trials
      of psychological interventions.
AB  - The randomized controlled trial (RCT) provides critical support for evidence
      based practice using psychological interventions. The control condition is the
      principal method of removing the influence of unwanted variables in RCTs. There
      is little agreement or consistency in the design and construction of control
      conditions. Because control conditions have variable effects, the results of RCTs
      can depend as much on control condition selection as on the experimental
      intervention. The aim of this paper is to present a framework for the selection
      and design of control conditions for these trials. Threats to internal validity
      arising from modern RCT methodology are reviewed and reconsidered. The strengths
      and weaknesses of several categories of control conditions are examined,
      including the ones that are under experimental control, the ones that are under
      the control of clinical service providers, and no-treatment controls.
      Considerations in the selection of control conditions are discussed and several
      recommendations are proposed. The aim of this paper is to begin to define
      principles by which control conditions can be selected or developed in a manner
      that can assist both investigators and grant reviewers.

PMID- 19602917
TI  - Functioning and disability in bipolar disorder: an extensive review.
AB  - BACKGROUND: Bipolar disorder has generally been regarded as having a better
      functional outcome than schizophrenia. However, studies have suggested low
      functioning in bipolar patients even when they are in clinical remission. Our aim
      was to determine the degree of functioning and disability in bipolar patients.
      Secondly, we reviewed factors potentially associated with the low functioning of
      bipolar patients. METHOD: The authors conducted an extensive Medline and Pubmed
      search of the published literature from 1980 up to December 2007, using a variety
      of search terms to find relevant articles. Bibliographies of retrieved papers
      were further analysed for publications of interest. Articles that reported
      clinically significant findings on functioning and disability, and research
      reports were reviewed in detail. RESULTS: From these articles, we determined that
      bipolar disorder is associated with significant impairment in work, family and
      social life, beyond the acute phases of the illness. The aspects that appear to
      increase the risk of low functioning and disability in bipolar patients are
      mainly subsyndromal symptoms and neurocognitive impairment, among others.
      CONCLUSIONS: Suitable pharmacological and psychological interventions may improve
      the level of functioning and reduce the disability in bipolar patients. Potential
      targets to be considered for intervention should be residual symptoms, comorbid
      conditions and neurocognitive deficits. Further research is required to better
      identify the factors that best predict functioning in bipolar patients.

PMID- 19602919
TI  - [HIV infection: treatment of naive patients].
AB  - Recently, the approach to initial therapy in naive patients has profoundly
      changed. The trend in 2008 suggests that HAART be started earlier than previously
      held. HAART should also be considered in selected patients with a CD4(+) count
      falling in the range 350-400 cells/microliter and in all subjects with a TCD4 (+)
      lower than 350 cells/microliter. Initial HAART provides a sufficiently broad
      range of choices, undoubtedly destined to further improve in the near future.
      However, such a choice has to take into account the patient's specific
      requirements and clinical picture, including comorbidity, risk factors for
      cardiovascular metabolic complications, simplicity and convenience of therapeutic
      regimen, and long-term tolerability.

PMID- 19602918
TI  - Prostate specific antigen in women with menstrual disturbances and fibrocystic
      mastopathy.
AB  - The objective of this study was to evaluate serum prostate specific antigen (PSA)
      levels in women with menstrual disturbances and fibrocystic mastopathy. A total
      of 114 women with fibrocystic breast disease with cysts <10 mm (group I), 62 with
      macrocysts >10 mm (group II) and 46 healthy volunteers, who served as control
      subjects, were recruited for this prospective study. Each patient underwent
      complete gynecological examination and had performed sonography of the breasts.
      Moreover menstrual pattern, serum levels of free and total PSA, LH, FSH, SHBG,
      PRL, estradiol, progesterone, TSH, T4, as well as serum total testosterone, were
      evaluated in each subject. We compared serum free and total PSA levels between
      women with different menstrual pattern within groups of women with micro- and
      macrocysts. We also evaluated correlations between serum free and total PSA and
      hormonal/descriptive variables. We found that, in group II, women with regular
      menses and polymenorrhea revealed significantly higher serum free PSA than women
      with oligomenorrhea and secondary amenorrhea. Moreover, we found a positive
      correlation between serum total testosterone and total PSA in the control group
      and between progesterone and total PSA in group II. Our data show that serum free
      PSA is increased in women with regular menstrual cycles and polymenorrhea. This
      later relationship refers to women with macrocysts. Further studies are required
      to clarify the relationships between serum PSA and menstrual disturbances in
      women with mastopathy.

PMID- 19602920
TI  - [Disappearance of Streptococcus pyogenes macrolide resistance in an area of
      northeastern Italy: a possible link with rational long-acting macrolide
      consumption].
AB  - Many studies have shown a correlation between higher consumption of long-acting
      macrolides and the development of resistance of S. pyogenes but, to our
      knowledge, no studies have reported the disappearance of S. pyogenes macrolide
      resistance. We evaluated the possible relationship between the rational use of
      long-acting macrolide consumption and the disappearance of S. pyogenes
      erythromycin resistance in an area of northeastern Italy, the district of
      Pordenone (approximately 300,000 inhabitants). The emerging use of new long
      acting macrolides, especially since 1993, has caused a great increase in total
      macrolide consumption (expressed as defined daily doses per 1,000 inhabitants per
      day; DDDs), followed by a steady increase in the percentage of S. pyogenes
      resistant to erythromycin (from 4% in 1994 to 56.3% in 2000). Subsequently, from
      2000 to 2007, the maintenance of steady-high DDDs of clarithromycin but low DDDs
      of azithromycin resulted in a sharp decrease in the percentage of S. pyogenes
      resistance to erythromycin (from 33.3% in 2001 to 0.2% in 2008). Disappearance of
      S. pyogenes erythromycin resistance in the last few years, compared with data of
      long-acting macrolide consumption from 2000 to 2007, suggests that S. pyogenes
      resistance to erythromycin is more likely associated with the specific type of
      compound used rather than with total consumption of long-acting macrolides.

PMID- 19602921
TI  - [Sexual exposure to HIV, sexual behaviour and use of pharmacological post
      exposure prophylaxis (PEP)].
AB  - In this study we examined the characteristics of 60 subjects (49 M and 11 F,
      average age 32.3) out of 195 post-exposure pharmacological prophylaxis (PEP) to
      HIV, taken in our hospital from 2001 to 2008. The above-mentioned subjects are
      sexually exposed (or presumably exposed) to HIV. We considered both their sexual
      intercourse behaviour and protective measures, and sought to infer some trends in
      sexual behaviour in Italy. All the subjects were monitored until 180 days after
      exposure, as established by the national guidelines. Only one of the 60 people
      presented a seroconversion (he dropped out after a 15-day follow-up and after an
      inadequate 19-day prophylaxis). Another subject, a homosexual male, never
      previously tested, resulted positive at time 0 both for HIV-Ab and syphilis tests
      (due to previous risk-sexual exposure), which caused the suspension of the
      prophylaxis. No HBV, HCV or syphilis seroconversion occurred. Two other
      homosexual males showed a previously latent positivity to syphilis tests at time
      0.

PMID- 19602922
TI  - Diarrhoea in children: aetiology and clinical aspects.
AB  - To determine the aetiology of diarrhoea in children younger than 5 years
      hospitalised for acute enteritis and to evidence the chief clinical aspects in
      correlation with different aetiological agents, a total of 402 children with
      acute diarrhoea were examined between February 2003 and December 2006 in the
      Paediatric Department of Sondrio Hospital. Faecal samples were collected and
      processed by routine microbiological and biochemical tests. For all patients the
      clinical signs and symptoms on admission were evidenced. Most of the patients
      (310/402, 77.1%) were infected by rotavirus, while of the remaining 82 (22.9%) 40
      were infected by salmonella species. In 42 patients, no bacterial agent was
      evidenced by microbiological tests. Clinical signs of mild dehydration were
      observed in 13 children during the hospital stay (all infected by rotavirus),
      while no case of metabolic acidosis, hypoglycaemia or hypovolaemic shock was
      documented. Elevated serum levels of uric acid were evidenced in 13/302 (4.3%) of
      patients with rotavirus infection, while only 1/82 (1.2%) rotavirus-negative
      children presented a minimal increase in serum uric acid level. Our retrospective
      study confirms the epidemiological and clinical importance of rotavirus as the
      main aetiological agent in hospitalised children younger than 5 years affected by
      acute diarrhoea. There also emerged a possible correlation between rotavirus
      infection and hyperuricaemia, probably connected with dehydration.

PMID- 19602924
TI  - Salvage therapy with tenofovir followed by adefovir maintenance in a cirrhotic
      patient with a lamivudine resistant HBV flare.
AB  - A 36 year old man with chronic hepatitis B and cirrhosis was admitted in our
      Department for the onset of jaundice, ascites and ALT flare (x 35 u.n.v.) while
      under lamivudine treatment. Serum HBV-DNA was 1.48 x 10(6) IU/ml and lamivudine
      (LAM) resistance mutations were present. Tenofovir (TDF) 300 mg/day was added to
      LAM after its off-label use was authorised. HBV-DNA decreased in a biphasic
      manner and became undetectable by day 45. A parallel improvement in ALT and
      bilirubin values was detected. Tenofovir was substituted with adefovir dipivoxil
      10 mg/day. Ten months after this switch HBV-DNA remained undetectable. Tenofovir
      is an effective salvage therapy for critically ill patients with LAM-resistant
      HBV flares and can be switched to adefovir after HBV-DNA becomes undetectable.
      Local cost and reimbursement policies are important determinants in antiviral
      therapy.

PMID- 19602926
TI  - Dicrocoelium dendriticum: a true infection?
AB  - Dicrocoelium dendriticum is a liver parasite of ruminants. Humans are
      occasionally infected by ingestion of intermediate hosts. We report a rare case
      of dicrocoeliasis in a 55-year-old woman who presented with eosinophilia and
      elevated bilirubin. Therapy with albendazole eradicated the parasite and
      normalized blood parameters.

PMID- 19602923
TI  - [Paucisymptomatic pneumonia due to Rothia mucilaginosa: case report and
      literature review].
AB  - Rothia mucilaginosa is a Gram-positive, coagulase-negative, encapsulated, non
      spore-forming coccus considered part of the commensal flora of the oral cavity
      and the upper respiratory tract in humans. Its involvement has been reported in
      an increasing spectrum of infections, above all among immunocompromised patients.
      To date, only 11 cases of pneumonia due to Rothia mucilaginosa have been
      described in the literature. The authors report a case of pneumonia due to Rothia
      mucilaginosa in a 72-year-old man with laryngeal cancer and review the published
      cases of pneumonia due to this pathogen.

PMID- 19602925
TI  - [Spontaneous and treatment-induced virological dynamic in the plasma, PBMC and
      liver tissue in a patient with chronic HBV and HCV coinfection].
AB  - Here it is reported the virological dynamic of HBV and HCV, identified in the
      plasma, peripheral blood mononuclear cells and tissue liver, in a patient with
      chronic HBV-HCV coinfection. A treatment with pegylated Interferon plus Ribavirin
      determined a sustained virological response for HCV in all the three studied
      compartments, but a reactivation of chronic HBV infection was observed. In fact,
      while at the first observation HBV-DNA was detectable only in the liver tissue,
      after antiviral therapy it was detectable in all the three compartments; moreover
      this HBV reactivation was associated with a hepatic flare. Then, the patient was
      treated with Entecavir, which has been determining the clearance of HBV from the
      peripheral compartments (plasma and PBMC) until today.

PMID- 19602927
TI  - [Syphilis in Ferrara in the nineteenth century].
AB  - In this article the authors highlight the behaviour of government authorities in
      the nineteenth century in Italy and especially in Ferrara to implement those
      measures deemed necessary to stem the spread of syphilis in epidemic form through
      the control of prostitution. Albeit discontinuously and until 1865, corrupted and
      infected women in Ferrara were assisted and treated by charitable institutions
      (Congregation of Charity, the Congregation of the Ladies of St. Vincent and the
      Sisters of Charity at the complex St. Mary of Consolation) since the Ferrara
      public hospital (Arcispedale S. Anna) could not accept or treat infected
      prostitutes for economic reasons and lack of beds. Subsequently, the hospital
      only treated prostitutes free of charge if they bore a certificate of poverty.
      The other infected prostitutes were sent to the sifilicomio in Modena. The
      authors also study mortality from syphilis in Ferrara from 1813 to 1899 in order
      to detect any significant differences according to age, sex and professional
      status and attempt to identify the stage of the disease (primary, secondary and
      tertiary), according to the terminology used by the doctors of that time.

PMID- 19602929
TI  - Clinical utility of progesterone receptor modulators and their effect on the
      endometrium.
AB  - PURPOSE OF REVIEW: In view of the spate of recent publications related to
      mifepristone and some second generation progesterone receptor modulators (PRMs),
      this appears to be an opportune time to view the clinical status of these
      compounds. RECENT FINDINGS: Randomized double-blind placebo-controlled trials
      have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914,
      Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment
      of uterine fibroids where they are associated with a reduction in pain, bleeding
      and improvement in quality of life and decrease in fibroid size. CDB-4124 is also
      efficacious in endometriosis. Long-term treatment with PRMs may be associated
      with endometrial thickening on ultrasound and there have been reports of
      endometrial hyperplasia. Several reassuring recent publications have done much to
      explain the mechanism underlying these endometrial changes. The most common
      histological finding is cystic glandular dilatation often associated with both
      admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This
      histology has not been previously encountered in clinical practice and should not
      be confused with endometrial hyperplasia. The endometrial thickness is related to
      this cystic glandular dilatation. SUMMARY: At this stage of development, PRMs
      cannot be administered for longer than 3 or 4 months. Even over this time, there
      is improvement of symptoms associated with fibroids and endometriosis. Clinicians
      and pathologists need to be aware that the endometrial thickening and
      histological appearance do not represent endometrial hyperplasia.

PMID- 19602930
TI  - Bibliography: Current world literature.

PMID- 19602932
TI  - Aesthetic surgery in Asians.
AB  - PURPOSE OF REVIEW: The article reviews literature on three distinct Asian facial
      aesthetic surgical procedures: Asian upper blepharoplasty, Asian augmentation
      rhinoplasty, and Asian skeletal facial contouring, which are considered to be
      unique in facial aesthetic procedures among Asians. RECENT FINDINGS: Asian upper
      blepharoplasty is not a Westernization procedure. Minimally invasive or
      noninvasive techniques such as use of continuous buried tarsal stitch have gained
      popularity. A separate incision for epicanthoplasty has been advocated. ePTFE as
      an alloplastic material has gained popularity in Asian augmentation rhinoplasty.
      Soft ePTFE sheets as augmentation material provide promise in the future. The
      popular choice for reduction malarplasty currently is to be able to perform
      procedure safely via intraoral approach. The current concept for lower facial
      reduction is a combined lateral mandibular reduction and reduction of angle of
      mandible and hypertrophic masseter muscle. SUMMARY: Three distinct sets of Asian
      facial aesthetic surgical procedures have been discussed via history, anatomy,
      technique, and current opinions. Familiarity with the culture, aesthetic,
      anatomic and technical components of these procedures is essential for a
      successful outcome.

PMID- 19602933
TI  - Current Opinion in Otolaryngology & Head and Neck Surgery. Current world
      literature.

PMID- 19602942
TI  - What's new in Shock, August 2009?

PMID- 19602943
TI  - A large-bolus injection, but not continuous infusion of sodium selenite improves
      outcome in peritonitis.
AB  - Administration of sodium selenite in septic shock has been associated with
      apparently conflicting results that may be related to different dosing schedules.
      Bolus administration, leading to a transient pro-oxidative effect, could limit
      the inflammatory reaction and improve outcomes. We studied 21 anesthetized,
      mechanically ventilated, invasively monitored, and fluid-resuscitated sheep. Nine
      hours after inducing peritonitis by injection of autologous feces, the animals
      were randomized into three groups: (i) bolus injection (2 mg selenium as
      selenite, followed by 0.06 microg . kg-1 . h-1, n = 7); (ii) continuous infusion
      (4 microg . kg-1 . h-1 selenium, n = 7), or (iii) control (n = 7). No
      vasopressors or antibiotics were administered. All animals were monitored until
      spontaneous death. Peak plasma selenium values reached 4 to 14 micromol . L-1.
      Compared with the other groups, sheep given a bolus of sodium selenite had
      delayed hypotension with better maintained cardiac index, delayed
      hyperlactatemia, fewer sepsis-induced microvascular alterations, and a prolonged
      survival time (21.9 [bolus group] vs. 18.4 [continuous group] and 18.3 h [control
      group], P < 0.05). Hence, in this model of septic shock, the administration of a
      large bolus of sodium selenite (rather than a continuous administration) resulted
      in beneficial effects, probably by a transient oxidative effect.

PMID- 19602944
TI  - Kidney, colon, and small intestine in thorax.

PMID- 19602945
TI  - Reduction mammoplasty with superolateral dermoglandular pedicle: details of 15
      years of experience.
AB  - The techniques of reduction mammoplasty are multiple and varied. Each one has
      advantages and disadvantages. With any of them, full preservation of vascularity
      and sensitizing of the nipple-areola complex (NAC) should be sought, as well as
      functionality of the breast. We present our 15 years' experience using the
      superolateral dermoglandular pedicle, a technique that fully preserves the
      integrity of the breast. During that 15-year period, we operated on 702 breasts
      in 356 patients, using the superolateral dermoglandular pedicle, with the NAC
      requiring a migration of 5 to 16 cm (mean: 9.2 cm), having resected breast tissue
      between 300 and 1380 g, (average: 660 g). The technique was used in women between
      16 and 63 years of age (average 37), who wanted breast reduction and who required
      a migration of the NAC greater than 5 cm. We had minor complications consisting
      of wound dehiscence (5.9%), scar hyperpigmentation (3.9%), fat necrosis (3.8%),
      hypertrophic scarring (3.1%), alterations in sensitivity (2.27%), and keloid
      scarring (0.5%). We had 9 cases of necrosis of the NAC (1.28%), of which 7 were
      partial (0.99%) and 2 were total (0.28%). Satisfaction with the results was 94%.
      The technique of reduction mammoplasty with a superolateral dermoglandular
      pedicle has been used in mammary hypertrophy and gigantomasty with excellent
      results. Its design is simple, its performance easy, and its aesthetic results
      are highly reproducible. The position of the pedicle allows full preservation of
      the vascularity, sensitivity, and functionality of the breast, and is therefore a
      highly recommendable technique.

PMID- 19602946
TI  - Management of inguinal lymphadenopathy: immediate sartorius transposition and
      reconstruction of recurrence with pedicled ALT flap.
AB  - Inguinal lymphadenectomy is associated with considerable morbidity, and several
      attempts have been made to minimize the morbidity by well-vascularized flaps of
      adequate bulk to obliterate the dead space and promote wound healing. In the case
      of recurrence, the overlying skin is usually involved and the reconstructive
      surgeon is confronted with exposed femoral vessels and complex groin defects. We
      report a series of 40 patients that underwent inguinal lymphadenectomy and
      immediate sartorius transposition for skin malignancies, and 4 patients with
      recurrence that was treated with radical surgical excision and pedicled
      anterolateral thigh flap (ATL). We examined complications such as infection, skin
      necrosis, lymphorea, lymphoedema, and wound healing time. The immediate sartorius
      transposition was associated with 7.5% infection rate, 5% superficial skin edge
      necrosis, 0% of persistent lymph, and 27.5% of mild lymphoedema. All ALT flaps
      survived completely and wounds healed uneventfully within 2 weeks without any
      signs of infection, seroma, or wound dehiscence.Sartorius and ALT flap are
      reliable methods to reconstruct the groin following inguinal lymphadenectomy.
      They ensure low complication rate with no donor site morbidity, and should be the
      first line treatment of immediate and secondary groin reconstruction,
      respectively.

PMID- 19602947
TI  - Residents' views of plastic surgery in the geriatric population: an objective
      needs assessment for graduate plastic surgery education.
AB  - BACKGROUND: This study was undertaken to identify educational needs for plastic
      surgery residents regarding the care of elderly patients. METHODS: A focus group
      of plastic surgery residents was conducted. Investigators coded the focus group
      transcript, using a "concept identification" technique and organized the coded
      concepts within the 6 general competencies of the Accreditation Council for
      Graduate Medical Education. Codes were then analyzed to determine whether they
      reflected an area of educational need. RESULTS: Eight residents participated.
      Investigators coded 118 concepts. Educational need was identified in 102 (86%) of
      the concepts, with medical knowledge identified as the area of greatest need.
      CONCLUSION: This study supports the need for improved education in geriatrics
      care at our program. This process facilitated the development of a new curriculum
      at our program and demonstrated that the concept coding technique is useful for
      analysis of focus groups for needs assessment in surgical education.

PMID- 19602948
TI  - Lower eyelid anatomy: an update.
AB  - The gross anatomy of the lower eyelid is analogous to that of the upper eyelid,
      however, the lower eyelid has a more simplified structure with less dynamic
      movement. Common malpositions of the lower eyelid include entropion and
      ectropion, rehabilitative surgery of which requires a thorough understanding of
      lower eyelid anatomy. Furthermore, precise anatomic knowledge is a prerequisite
      for both reconstructive and cosmetic lower eyelid surgery in order for it to be
      performed appropriately. In this review, we present the clinical anatomy of the
      structures of the lower eyelid, as well as highlighting relevant surgical
      implications. Featured here are the structure of the different eyelid lamellae,
      the lower eyelid retractors and their relations, the orbital septum, fat pad
      compartments, and Lockwood ligament.

PMID- 19602949
TI  - Upper eyelid anatomy: an update.
AB  - Eyelid surgery necessitates a thorough knowledge of eyelid anatomy. Recent
      contributions to the literature have significantly advanced our understanding of
      eyelid anatomy. In this review, we present an update of the anatomy and the
      implications for upper eyelid surgery. Aspects to be covered include the levator
      aponeurosis, Muller's muscle, lamina propria mucosae of conjunctiva, orbital
      septum, myoneural junction of the levator palpebrae superioris muscle, adipose
      tissue, and the ligament system.

PMID- 19602950
TI  - Clinical outcome after pedicled segmental pectoralis major island flaps for head
      and neck reconstruction.
AB  - The pectoralis major is reliable for reconstruction of large defects in the head
      and neck area. In 2001, we introduced a muscle-sparing technique with
      preservation of the clavicular part of the muscle. So far, we did not report on
      its reliability and clinical outcome at the receptor site.Fifty-four pedicled
      segmental pectoralis major island flaps were used in 53 patients, from 2001
      through 2006. As outcome measures, we studied the overall rate of complications,
      the rate of major complications, and the final outcome at the receptor sites. We
      differentiated for the types of complications and assessed operation indication
      (primary vs. salvage procedure), site of reconstruction, previous radiotherapy,
      and completeness of tumor excision as possible risk factors for complications. We
      compared our findings to those of a meta-analysis of 16 other
      studies.Complications at the receptor site were observed after 21 of the 54
      operations (0.39). Eleven of these cases (0.52) required repeated surgery that
      was successful in 8 cases (0.72). Conservative treatment was successful in 8
      cases (0.80). Final outcome was successful in 49 of the 54 operations (0.91).
      Previous radiotherapy was a significant risk factor for persisting complications.
      Salvage procedures were a significant risk factor for developing clinical
      fistulas and the risk of partial flap loss was significantly correlated with
      nonhypopharyngeal reconstructions. Our results were comparable with those found
      in the meta-analysis.Our muscle-sparing technique proved to be reliable with
      clinical results comparable with conventional techniques in addition to function
      preservation at the donor site.

PMID- 19602951
TI  - Delayed skin grafting utilizing autologous banked tissue.
AB  - In performing bowel flaps for voice reconstruction, it is common practice to
      delay skin grafting to allow for swelling and monitoring. Harvesting the skin
      graft at the time of reconstruction and banking it at its donor site allows for
      later transfer at bedside. Ten patients between January and July of 2006 had skin
      harvested from their thigh at the time of intestinal transfer and banked at the
      donor site. Transfer of the graft from donor to recipient site was carried out at
      bedside between the third and eighth postoperative day with sedation and
      analgesia. Elevation of the graft was well tolerated and take was over 95% in all
      cases without related complications. At follow-up between 5 and 12 months all
      grafts had healed. This is a reliable technique for skin storage in diverse
      clinical applications or when traditional skin banking cannot be performed
      because of tissue banking regulations.

PMID- 19602952
TI  - Estrogen deficiency and tobacco smoke exposure promote matrix metalloproteinase
      13 activation in skin of aging B6 mice.
AB  - Estrogen deficiency may contribute to extracellular matrix turnover in skin. This
      has led previous authors to postulate that aged skin heals less efficiently when
      compared to younger skin. Also, cigarette smokers have been shown to heal less
      efficiently than nonsmokers. Matrix metalloproteinase (MMP)-13, an enzyme that
      participates in the degradation of the extracellular matrix, has been implicated
      in physiologic aging and wound healing. This study investigates the effects of
      smoke exposure and estrogen deficiency on MMP-13 in young and aged female mouse
      skin. Young and aged female C57Bl/6J mice were ovariectomized. They were then
      randomly administered either 17beta-estradiol (E2) or placebo pellets. Half the
      animals in each age group were further randomized to exposure to cigarette smoke
      for a period of 6 months. Smoking and estrogen deficiency increased MMP-13
      protein and activity in aged skin. The tissue inhibitors of metalloproteinases,
      which inhibit MMPs, activity was unchanged across all groups. E2 replacement
      decreased the actual level of MMP-13 protein and activity. We also found an
      increased collagen content and decreased ER receptor protein level in aged, smoke
      exposed female mice. Our experimental data show that tobacco smoke exposure and
      estrogen deficiency are additive risk factors for promoting increased activity of
      MMP-13 in aged skin. These findings suggest that MMP-13 functions as a mediator
      of smoke-induced skin injury in susceptible, aged experimental female mice.

PMID- 19602953
TI  - General anesthesia increases temporal precision and decreases power of the
      brainstem auditory-evoked response-related segments of the electroencephalogram.
AB  - BACKGROUND: Brainstem auditory-evoked responses (BAEP) have been reported to be
      unchanged in the presence of drugs used for induction and maintenance of general
      anesthesia. The aim of this study was to investigate if the signal segments after
      the auditory stimulus that are used to average the evoked response change under
      the influence of general anesthesia. METHODS: BAEPs of 156 patients scheduled for
      elective surgery under general anesthesia were investigated. Anesthetic regimen
      was randomized as a combination of one of four hypnotic drugs supplemented by one
      of four opioids. Signal segments after the auditory stimulus were obtained at six
      different periods of anesthesia. Power and phase properties of wavelet-filtered
      single-sweep auditory-evoked activity accounting for the waveform of the averaged
      BAEP wave V and the stability of amplitude and latency of the averaged BAEP wave
      V over periods were analyzed. RESULTS: Amplitude and latency of wave V change
      slightly with no significant difference between the periods. During anesthesia,
      however, the power of single sweeps is significantly reduced, whereas phase
      locking properties of the according signal segments are significantly enhanced.
      This effect is independent of the anesthetic or opioid used. CONCLUSIONS: General
      anesthesia affects phase and power of the segments of the electroencephalogram
      related to BAEP wave V. This study's results support the idea that temporally
      precise responses from a large number of neurons in the brainstem might play a
      crucial role in encoding and passing sensory information to higher subcortical
      and cortical areas of the brain.

PMID- 19602954
TI  - Supraclavicular approach is an easy and safe method of subclavian vein
      catheterization even in mechanically ventilated patients: analysis of 370
      attempts.
AB  - BACKGROUND: Central venous catheters are commonly inserted for hemodynamic
      monitoring, volume monitoring, administration of medications, long-term total
      parenteral nutrition, access for renal replacement therapy, cardiopulmonary
      resuscitation, and difficult peripheral catheterization. The primary outcome of
      this study was to define venipuncture, catheterization and entire procedure
      success rates, and finally complication rate of subclavian venous catheterization
      via the supraclavicular approach with special focus on mechanically ventilated
      patients. The secondary outcome was to potentially make recommendations regarding
      this technique of central venous catheterization in mechanically ventilated
      patients. METHODS: The methodology of this prospective cohort study included
      subclavian venous catheterization via the supraclavicular approach. The technique
      of cannulation was the same for both the right and left sides, but the right
      claviculosternocleidomastoid angle was the preferred catheterization site. All
      procedures were performed by the first three authors, each of whom had different
      levels of experience. Each physician had performed at least 20 procedures before
      starting the study. RESULTS: In the majority of patients, venipuncture occurred
      during the first attempt. In 362 patients, catheterization attempts were
      performed, in whom 311 catheterizations (85.6%) were successful during the first
      attempt. The overall subclavian venous catheterization via supraclavicular
      approach procedure complication rate reached 1.7% (95% confidence interval 0.6
      3.6%). The overall subclavian venous catheterization via the supraclavicular
      approach procedure success rate reached 88.9% (95% confidence interval 85.1
      91.9%, n = 359). CONCLUSIONS: Subclavian venous catheterization via the
      supraclavicular approach is an excellent method of central venous access in
      mechanically ventilated patients. The procedure success rate and the significant
      complication rate are comparable to other techniques of central venous
      catheterization.

PMID- 19602955
TI  - Intravenous infusion tests have limited utility for selecting long-term drug
      therapy in patients with chronic pain: a systematic review.
AB  - Since the first description in the early 1990s, the scope of intravenous
      infusions tests has expanded to encompass multiple drug classes and indications.
      Purported advantages of these tests include elucidating mechanisms of pain,
      providing temporary relief of symptoms, and usefulness as prognostic tools in
      guiding drug therapy. In an attempt to discern the value of these tests, the
      authors conducted a systematic review to explore the rationale and evidence
      behind the following intravenous infusion tests: lidocaine, ketamine, opioid, and
      phentolamine. The studies evaluating all intravenous infusion tests were
      characterized by lack of standardization, wide variations in outcome measures,
      and methodological flaws. The strongest evidence found was for the intravenous
      lidocaine test, with the phentolamine test characterized by the least convincing
      data. Whereas intravenous opioid infusions are the most conceptually appealing
      test, their greatest utility may be in predicting poor responders to sustained
      release formulations.

PMID- 19602956
TI  - Performance improvement system and postoperative corneal injuries: incidence and
      risk factors.
AB  - BACKGROUND: The authors' department conducted a performance improvement
      initiative aimed to reduce the rate of perioperative corneal injuries. This study
      reports the effects of the initiative and examines the risk factors for corneal
      injury. METHOD: The rate of corneal injuries during nonophthalmologic procedures
      under anesthesia was compared between the two time periods: preinitiative
      baseline (August 1, 2005-December 31, 2005) and initiative period (January 1,
      2006-April 30, 2007). To examine the risk factors for corneal injury, a nested
      case-control study with a 2:1 matched-set design was separately performed and
      included cases between January 1, 2006 and July 31, 2008. RESULTS: During the
      baseline period, the corneal injury rate was 1.51 per 1,000, and it decreased to
      0.79 per 1,000 during the performance initiative (P = 0.008). Independent risk
      factors were longer anesthetics (odds ratio = 1.2, 95% confidence interval (CI)
      1.1-1.3 per 30 min), lower American Society of Anesthesiologists physical status
      (odds ratio 0.5, 95% CI 0.3-0.8 for American Society of Anesthesiologists
      physical status 3-4 vs. 1-2), and student nurse anesthetist as a primary
      anesthesia provider (odds ratio 2.6, 95% CI 1.3-5.0). CONCLUSION: Corneal injury
      rate in our institution was significantly reduced and remains at low levels long
      after initiation of perioperative eye care improvement initiative. The higher
      rate of corneal injuries among student nurse anesthetists highlights the
      importance of standardizing education and supervision among all anesthesia
      providers. We believe that our model of performance improvement initiative can be
      used to improve other perioperative outcomes.

PMID- 19602959
TI  - Anesthesia for noncardiac surgery in adults with congenital heart disease.

PMID- 19602957
TI  - Depletion of calcium stores in injured sensory neurons: anatomic and functional
      correlates.
AB  - BACKGROUND: Painful nerve injury leads to disrupted Ca signaling in primary
      sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This
      study examines potential causes and functional consequences of Ca store
      limitation after injury. METHODS: Neurons were dissociated from axotomized fifth
      lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve
      ligation that produced hyperalgesia, and they were compared to neurons from
      control animals. Intracellular Ca levels were measured with Fura-2
      microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural
      morphology was analyzed by electron microscopy of nondissociated dorsal root
      ganglia, and intracellular electrophysiological recordings were obtained from
      intact ganglia. RESULTS: Live neuron staining with BODIPY FL-X thapsigargin
      (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum
      Ca-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons.
      Immunocytochemical labeling for the ER Ca-binding protein calreticulin was
      unaffected by injury. Total length of ER profiles in electron micrographs was
      reduced by 53% in small axotomized L5 neurons, but it was increased in L4
      neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less
      frequently in axotomized neurons. Ca-induced Ca release, examined by
      microfluorometry with dantrolene, was eliminated in axotomized neurons.
      Pharmacologic blockade of Ca-induced Ca release with dantrolene produced
      hyperexcitability in control neurons, confirming its functional importance.
      CONCLUSIONS: After axotomy, ER Ca stores are reduced by anatomic loss and
      possibly diminished sarco-endoplasmic reticulum Ca-ATPase. The resulting
      disruption of Ca-induced Ca release and protein synthesis may contribute to the
      generation of neuropathic pain.

PMID- 19602961
TI  - Prognostic value of brain natriuretic peptide in noncardiac surgery: a meta
      analysis.
AB  - BACKGROUND: The prognostic role of brain natriuretic peptide (BNP) measurement
      before noncardiac surgery is unclear. The authors therefore performed a meta
      analysis of studies in patients undergoing noncardiac surgery to assess the
      prognostic value of elevated BNP or N-terminal pro-BNP (NT-proBNP) levels in
      predicting mortality and major adverse cardiovascular events (MACE) (cardiac
      death or nonfatal myocardial infarction). METHODS: Unrestricted searches of
      MEDLINE and EMBASE bibliographic databases were performed using the terms "brain
      natriuretic peptide," "b-type natriuretic peptide," "BNP," "NT-proBNP," and
      "surgery." In addition, review articles, bibliographies, and abstracts of
      scientific meetings were manually searched. The meta-analysis included
      prospective studies that reported on the association of BNP or NT-proBNP and
      postoperative major adverse cardiovascular event (MACE) or mortality. The study
      endpoints were MACE, all-cause mortality, and cardiac mortality at short-term
      (less than 43 days after surgery) and longer-term (more than 6 months) follow-up.
      A random-effects model was used to pool study results; funnel-plot inspection was
      done to evaluate publication bias; Cochrane chi-square test and I testing was
      used to test for heterogeneity. RESULTS: Data from 15 publications (4,856
      patients) were included in the analysis. Preoperative BNP elevation was
      associated with an increased risk of short-term MACE (OR 19.77; 95% confidence
      interval [CI] 13.18-29.65; P < 0.0001), all-cause mortality (OR 9.28; 95% CI 3.51
      24.56; P < 0.0001), and cardiac death (OR 23.88; 95% CI 9.43-60.43; P < 0.00001).
      Results were consistent for both BNP and NT-proBNP. Preoperative BNP elevation
      was also associated with an increased risk of long-term MACE (OR 17.70; 95% CI
      3.11-100.80; P < 0.0001) and all-cause mortality (OR 4.77; 95% CI 2.99-7.46; P <
      0.00001). CONCLUSIONS: Elevated BNP and NT-proBNP levels identify patients
      undergoing major noncardiac surgery at high risk of cardiac mortality, all-cause
      mortality, and MACE.

PMID- 19602958
TI  - Axotomy depletes intracellular calcium stores in primary sensory neurons.
AB  - BACKGROUND: The cellular mechanisms of neuropathic pain are inadequately
      understood. Previous investigations have revealed disrupted Ca signaling in
      primary sensory neurons after injury. The authors examined the effect of injury
      on intracellular Ca stores of the endoplasmic reticulum, which critically
      regulate the Ca signal and neuronal function. METHODS: Intracellular Ca levels
      were measured with Fura-2 or mag-Fura-2 microfluorometry in axotomized fifth
      lumbar (L5) dorsal root ganglion neurons and adjacent L4 neurons isolated from
      hyperalgesic rats after L5 spinal nerve ligation, compared to neurons from
      control animals. RESULTS: Endoplasmic reticulum Ca stores released by the
      ryanodine-receptor agonist caffeine decreased by 46% in axotomized small neurons.
      This effect persisted in Ca-free bath solution, which removes the contribution of
      store-operated membrane Ca channels, and after blockade of the mitochondrial,
      sarco-endoplasmic Ca-ATPase and the plasma membrane Ca ATPase pathways. Ca
      released by the sarco-endoplasmic Ca-ATPase blocker thapsigargin and by the Ca
      ionophore ionomycin was also diminished by 25% and 41%, respectively. In contrast
      to control neurons, Ca stores in axotomized neurons were not expanded by neuronal
      activation by K depolarization, and the proportionate rate of refilling by sarco
      endoplasmic Ca-ATPase was normal. Luminal Ca concentration was also reduced by
      38% in axotomized neurons in permeabilized neurons. The adjacent neurons of the
      L4 dorsal root ganglia showed modest and inconsistent changes after L5 spinal
      nerve ligation. CONCLUSIONS: Painful nerve injury leads to diminished releasable
      endoplasmic reticulum Ca stores and a reduced luminal Ca concentration. Depletion
      of Ca stores may contribute to the pathogenesis of neuropathic pain.

PMID- 19602960
TI  - Anesthesia for cesarean delivery and learning disabilities in a population-based
      birth cohort.
AB  - BACKGROUND: Anesthetics administered to immature brains may cause
      histopathological changes and long-term behavioral abnormalities. The association
      between perinatal exposure to anesthetics during Cesarean delivery (CD) and
      development of learning disabilities (LD) was determined in a population-based
      birth cohort. METHODS: The educational and medical records of all children born
      to mothers residing in five townships of Olmsted County, Minnesota from 1976-1982
      and remaining in the community at age 5 were reviewed to identify those with LDs.
      Cox proportional hazards regression was used to compare rates of LD between
      children delivered vaginally and via CD (with general or regional anesthesia).
      RESULTS: Of the 5,320 children in this cohort, 497 were delivered via CD (under
      general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD
      depended on mode of delivery (P = 0.050, adjusted for sex, birth weight,
      gestational age, exposure to anesthesia before age 4 yr, and maternal education).
      LD risk was similar in children delivered by vagina or CD with general
      anesthesia, but was reduced in children receiving CD with regional anesthesia
      (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for
      comparison of CD under regional anesthesia compared to vaginal delivery).
      CONCLUSION: Children exposed to general or regional anesthesia during CD are not
      more likely to develop LD compared to children delivered vaginally, suggesting
      that brief perinatal exposure to anesthetic drugs does not adversely affect long
      term neurodevelopmental outcomes. The risk of LD may be lower in children
      delivered by CD whose mothers received regional anesthesia.

PMID- 19602963
TI  - Physical examination trumps mediastinoscopy in diagnosing maffucci syndrome: a
      rare cause of mediastinal mass.

PMID- 19602964
TI  - Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus
      blocks: a meta-analysis of randomized trials.
AB  - The effect of adding clonidine to local anesthetics for nerve or plexus blocks
      remains unclear. The authors searched for randomized placebo-controlled trials
      testing the impact of adding clonidine to local anesthetics for peripheral single
      injection nerve or plexus blocks in adults undergoing any surgery (except eye)
      without general anesthesia. Twenty trials (1,054 patients, 573 received
      clonidine) published 1992-2006 tested plexus (14 brachial, 1 cervical) and nerve
      blocks (2 sciatic/femoral, 1 midhumeral, 1 ilioinguinal/iliohypogastric, 1
      ankle). Clonidine doses ranged from 30 to 300 microg; most patients received 150
      microg. Clonidine prolonged the duration of postoperative analgesia (weighted
      mean difference 122 min; 95% confidence interval [CI] 74-169), sensory block
      (weighted mean difference 74 min; 95% CI 37-111), and motor block (weighted mean
      difference 141 min; 95% CI 82-199). In a subgroup of patients receiving an
      axillary plexus block, these effects were independent of whether clonidine was
      added to an intermediate or a long-acting local anesthetic. Clonidine increased
      the risk of arterial hypotension (odds ratio 3.61; 95% CI 1.52-8.55; number
      needed-to-harm 11), orthostatic hypotension or fainting (odds ratio 5.07; 95% CI
      1.20-21.4; number-needed-to-harm 10), bradycardia (odds ratio 3.09; 95% CI 1.10
      8.64; number-needed-to-harm 13), and sedation (odds ratio 2.28; 95% CI 1.15-4.51;
      number-needed-to-harm 5). There was a lack of evidence of dose-responsiveness for
      beneficial or harmful effects. Clonidine added to intermediate or long-acting
      local anesthetics for single-shot peripheral nerve or plexus blocks prolongs
      duration of analgesia and motor block by about 2 h. The increased risk of
      hypotension, fainting, and sedation may limit its usefulness. Dose-responsiveness
      remains unclear.

PMID- 19602962
TI  - Lumbar sympathetic blockade in children with complex regional pain syndromes: a
      double blind placebo-controlled crossover trial.
AB  - BACKGROUND: Sympathetic blockade is used in the management of complex regional
      pain syndromes in children, but there are no data on the efficacy or mechanism(s)
      by which it produces pain relief. The purpose of this study is to compare the
      efficacy of lidocaine administered by lumbar sympathetic to IV route. METHODS:
      Under general anesthesia, children with unilateral lower limb complex regional
      pain syndromes received catheters along the lumbar sympathetic chain. In a double
      blind placebo-controlled crossover design, patients received IV lidocaine and
      lumbar sympathetic saline or lumbar sympathetic lidocaine and IV saline.
      Spontaneous and evoked pain ratings and sensory thresholds were assessed before
      and after these two lidocaine/saline doses and between routes of lumbar
      sympathetic blockade and IV. RESULTS: Twenty-three patients, ages 10-18 yr, were
      enrolled. There was evidence for reduction of mean pain intensity of allodynia to
      brush (mean -1.4, 95% confidence interval [CI] -2.5 to -0.3) and to pinprick
      temporal summation (mean -1.3, 95% CI -2.5 to -0.2) with lidocaine treatment via
      the lumbar sympathetic blockade compared to IV route. Lumbar sympathetic blockade
      also produced significant reduction in pain intensity compared to pretreatment
      values of allodynia to brush, pinprick and pinprick temporal summation and verbal
      pain scores. IV lidocaine did not produce significant changes in spontaneous and
      evoked pain intensity measurements compared to pretreatment values. There were no
      carryover effects as assessed by route-by-period interaction. CONCLUSIONS: Under
      the conditions of this study, the results provide some direct evidence that a
      component of pain may be mediated by abnormal sympathetic efferent activity.

PMID- 19602965
TI  - Oxygen tissue saturation is lower in nonsurvivors than in survivors after early
      resuscitation of septic shock.
AB  - BACKGROUND: Growing evidence suggests that the microvascular dysfunction is the
      key element of the pathogenesis of septic shock. This study's purpose was to
      explore whether the outcome of septic shock patients after early resuscitation
      using early goal-directed therapy is related to their muscle tissue oxygenation.
      METHODS: Tissue oxygen saturation (Sto2) was monitored in septic shock patients
      using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology,
      Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values
      were collected at the first measurement done after the macrohemodynamic variables
      (mean arterial pressure, urine output, central venous saturation in oxygen) were
      optimized. RESULTS: After the hemodynamic variables were corrected, no difference
      was observed between the nonsurvivors and survivors, with the exception of pulse
      oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values
      were significantly lower in the nonsurvivors than in the survivors (73% [68-82%]
      vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2
      (P = 0.7). CONCLUSIONS: In septic shock patients, tissue oxygen saturation below
      78% is associated with increased mortality at day 28. Further investigations are
      required to determine whether the correction of an impaired level of tissue
      oxygen saturation may improve the outcome of these patients.

PMID- 19602966
TI  - Influence of vancomycin on renal function in critically ill patients after
      cardiac surgery: continuous versus intermittent infusion.
AB  - BACKGROUND: Vancomycin is frequently used in clinical practice to treat severe
      wound and systemic infections caused by Gram-positive bacteria after cardiac
      surgery. The drug is excreted almost entirely by glomerular filtration and might
      exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of
      vancomycin during continuous versus intermittent administration. METHODS: The
      authors analyzed 149 patients admitted to the intensive care unit during a 5-yr
      period. All patients were treated at the intensive care unit after elective open
      heart surgery. Thirty patients received a dosage of 1325 +/- 603 mg/d vancomycin
      (range 300-3400 mg/d) by intermittent infusion, and 119 patients received a mean
      dosage of 1935 +/- 688 mg/d (range 352-3411 mg/d) by continuous infusion.
      RESULTS: Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent
      treatment group and in 33 patients (27.7%) in the continuous treatment group (P =
      0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin
      administration was required for 9 patients (9 of 30; 30%) in the intermittent
      treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group
      (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum
      concentration (DeltaVancoC) induced an average change of 0.04 mg/dl in creatinine
      (DeltaCrea) in the intermittent treatment group versus 0.006 mg/dl in the
      continuous treatment group (P < 0.001). CONCLUSIONS: The data show that both the
      intermittent and also the continuous application modality of vancomycin are
      associated with deterioration of renal function in critically ill patients after
      cardiac surgery. However, continuous infusion showed the tendency to be less
      nephrotoxic than the intermittent infusion of vancomycin.

PMID- 19602967
TI  - Quantitative immunohistology: tissue section thickness, another glitch in the
      path to standardization.

PMID- 19602968
TI  - Desmoplastic small round cell tumor of the kidney mimicking Wilms tumor: a case
      report and review of the literature.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, malignant
      neoplasm usually present with the widespread abdominal serosal involvement and
      affects mainly adolescents and young adults. When presenting within visceral
      organs, as kidney, the diagnosis of DSRCT imposes significant difficulties. We
      present a case of primary DSRCT of the kidney in a 10-year-old boy mimicking
      clinically and pathologically Wilms tumor. The tumor showed morphologic and
      immunohistochemical features of DSRCT and the presence of the Ewing sarcoma and
      Wilm tumor 1 fusion transcripts resulting from the t(11;22) (p13;q12) reciprocal
      translocation. DSRCT should be considered in the differential diagnosis of Wilm
      tumor and other small blue-round cell tumors of the kidney.

PMID- 19602969
TI  - Aspergillus immunohistochemistry of culture-proven fungal tissue isolates shows
      high cross-reactivity.
AB  - Increased use of immunosuppressive drugs has broadened the range and increased
      the incidence of invasive fungal diseases. Successful therapy relies on early
      diagnosis; however, fungal organisms show overlapping morphology on histologic
      sections. As commercially available fungal immunohistochemistry (IHC) has been
      validated for crossreactivity with few other fungi, we ran Aspergillus and
      Candida IHCs on formalin-fixed, paraffin-embedded tissue of fungal cases. The
      cases had also been cultured from fresh tissue submitted to the clinical
      microbiology laboratory. Commercially available polyclonal and monoclonal
      Aspergillus and Candida IHCs were run with antigen retrieval on 16 culture
      confirmed fungal cases (9 Aspergillus, 2 Candida, 2 Bipolaris, 1 Fusarium, 1
      Curvularia, and 1 Rhizopus). Three additional cases, which stained positive for
      Zygomycete IHC at the Centers for Disease Control and Prevention, which had not
      been confirmed by culture, were also tested against the antibodies. Preabsorption
      controls with formalin-fixed fungi were run on 2 cases. Fifteen of the 16 culture
      confirmed cases stained with the polyclonal Aspergillus antibody, whereas only 7
      of 14 cases stained with the monoclonal Aspergillus antibody. Sensitivities and
      specificities for the polyclonal and monoclonal Aspergillus antibodies were 100%
      and 29%, and 43% and 14%, respectively. Two Zygomycete IHC Centers for Disease
      Control and Prevention cases stained strongly positive for monoclonal
      Aspergillus. Although Aspergillus cultures were often correctly identified on
      IHC, false positive staining was seen with both polyclonal and monoclonal
      Aspergillus antibodies. The number of culture-confirmed Candida cases was too low
      to adequately evaluate sensitivity. More accurate and reliable fungal IHCs,
      including those for Zygomycete staining, are needed.

PMID- 19602970
TI  - Chromosome 1p and 19q deletions in glioblastoma multiforme.
AB  - CONTEXT: Deletions on chromosomes 1p and 19q have been shown to correlate with
      prognosis and chemosensitivity in anaplastic oligodendrogliomas. In glioblastoma
      multiforme (GBM), the impact on prognosis of these alterations in GBM is unclear.
      OBJECTIVE: The purpose of this study was to identify patients with GBM who had
      evidence of 1p or 19q deletions by fluorescence in situ hybridization, and
      correlate these results with clinical findings and survival. DESIGN: Three
      hundred thirty-seven GBM resected between 2001 and 2006 were evaluated using
      fluorescence in situ hybridization to identify deletions on chromosomes 1p and
      19q. Cox regression was used to compare survival between these 2 groups and a
      control group of 1p and 19q intact tumors. RESULT: Seventeen (5.1%) patients (9
      males; mean age at diagnosis=61 y, range: 35 to 84 y) were found to have 1p
      deletions; 8 patients (47.1%) received chemotherapy and 13 patients received
      radiation therapy. The mean survival for this group was 10.8 months (range: 1 to
      50 mo). Eighteen (5.3%) patients (11 females; mean=56 y, range: 25 to 76 y) had
      19q deletions; 9 patients (50%) received chemotherapy and 8 patients were known
      to have had radiation therapy. The mean survival of this group was 8.4 months
      (range: 1 to 17 mo). A control group of 20 patients (13 males; mean=60 y, range:
      40 to 80 y) was selected, 8 patients (40%) of who received chemotherapy and 12
      patients were known to have had radiation therapy. The mean survival in this
      group was found to be 16.4 months (1 to 59 mo). Nine (3.7%) tumors had
      codeletions of 1p and 19q and were not evaluated in this study. Isolated 1p and
      19q deletions did not significantly correlate with survival. Adjusting for sex,
      age, and chemotherapy, the 19q-deleted group had a significantly lower survival
      (hazard ratio =2.8, P=0.025) than the other groups. CONCLUSIONS: The incidence of
      isolated 1p or 19q deletions among GBM in the current study was 6.2% and 5.3%,
      respectively. In contrast to anaplastic oligodendrogliomas, 1p and 19q deletions
      alone were not found to improve survival of patients with GBM; however, when
      adjusted for age, sex, and chemotherapy, 19q deletions seem to negatively impact
      survival.

PMID- 19602971
TI  - No child left behind: Enrolling children and adults simultaneously in critical
      care randomized trials.
AB  - OBJECTIVE: : Randomized clinical trials of novel critical care interventions are
      currently tested in children only after documenting their safety in adults.
      Although this practice may protect children from research risks, it may
      paradoxically threaten children's well-being by depriving them of evidence to
      guide their care. We sought to evaluate the ethical, methodologic, and practical
      arguments for and against studying critical care interventions in adults and
      children simultaneously rather than sequentially. DATA SOURCE: : Empirical
      studies and conceptual arguments germane to the objective were reviewed. DATA
      EXTRACTION AND SYNTHESIS: : Children are traditionally viewed as "participants of
      last resort" due to their vulnerability and decisional incapacity. However,
      critically ill adults commonly share similar features. Thus, structured risk
      assessments used by Institutional Review Boards to determine the adequacy of
      research protections for critically ill adults can also help protect children.
      From a methodologic perspective, interventions may be tested simultaneously in
      children and adults by enrolling children as a prespecified subgroup within a
      larger adult randomized clinical trial or by enrolling children in a separate
      trial conducted in parallel. Both approaches raise practical and analytical
      challenges that can frequently be met. For example, investigators might choose
      outcome measures that are appropriate for both adults and children. Additionally,
      using Bayesian approaches to link the estimates of treatment effects in children
      to the values observed in adults may enhance the statistical power to detect
      pediatric-specific effects. Finally, centralized Institutional Review Boards and
      data monitoring centers may alleviate practical concerns with conducting trials
      among adults and children simultaneously. CONCLUSIONS: : The current standard of
      testing critical care interventions in adults before children rests on tenuous
      ethical arguments and is entrenched by the methodologic and logistic barriers
      encountered with alternative approaches. However, these barriers will frequently
      be surmountable. We therefore propose that the default paradigm be changed such
      that interventions are examined routinely in critically ill children and adults
      simultaneously unless unique reasons exist to the contrary.

PMID- 19602972
TI  - Dynamic changes in arterial waveform derived variables and fluid responsiveness
      in mechanically ventilated patients: a systematic review of the literature.
AB  - OBJECTIVES: : A systematic review of the literature to determine the ability of
      dynamic changes in arterial waveform-derived variables to predict fluid
      responsiveness and compare these with static indices of fluid responsiveness. The
      assessment of a patient's intravascular volume is one of the most difficult tasks
      in critical care medicine. Conventional static hemodynamic variables have proven
      unreliable as predictors of volume responsiveness. Dynamic changes in systolic
      pressure, pulse pressure, and stroke volume in patients undergoing mechanical
      ventilation have emerged as useful techniques to assess volume responsiveness.
      DATA SOURCES: : MEDLINE, EMBASE, Cochrane Register of Controlled Trials and
      citation review of relevant primary and review articles. STUDY SELECTION: :
      Clinical studies that evaluated the association between stroke volume variation,
      pulse pressure variation, and/or stroke volume variation and the change in stroke
      volume/cardiac index after a fluid or positive end-expiratory pressure challenge.
      DATA EXTRACTION AND SYNTHESIS: : Data were abstracted on study design, study
      size, study setting, patient population, and the correlation coefficient and/or
      receiver operating characteristic between the baseline systolic pressure
      variation, stroke volume variation, and/or pulse pressure variation and the
      change in stroke index/cardiac index after a fluid challenge. When reported, the
      receiver operating characteristic of the central venous pressure, global end
      diastolic volume index, and left ventricular end-diastolic area index were also
      recorded. Meta-analytic techniques were used to summarize the data. Twenty-nine
      studies (which enrolled 685 patients) met our inclusion criteria. Overall, 56% of
      patients responded to a fluid challenge. The pooled correlation coefficients
      between the baseline pulse pressure variation, stroke volume variation, systolic
      pressure variation, and the change in stroke/cardiac index were 0.78, 0.72, and
      0.72, respectively. The area under the receiver operating characteristic curves
      were 0.94, 0.84, and 0.86, respectively, compared with 0.55 for the central
      venous pressure, 0.56 for the global end-diastolic volume index, and 0.64 for the
      left ventricular end-diastolic area index. The mean threshold values were 12.5 +/
      1.6% for the pulse pressure variation and 11.6 +/- 1.9% for the stroke volume
      variation. The sensitivity, specificity, and diagnostic odds ratio were 0.89,
      0.88, and 59.86 for the pulse pressure variation and 0.82, 0.86, and 27.34 for
      the stroke volume variation, respectively. CONCLUSIONS: : Dynamic changes of
      arterial waveform-derived variables during mechanical ventilation are highly
      accurate in predicting volume responsiveness in critically ill patients with an
      accuracy greater than that of traditional static indices of volume
      responsiveness. This technique, however, is limited to patients who receive
      controlled ventilation and who are not breathing spontaneously.

PMID- 19602973
TI  - Incidence and outcomes of acute kidney injury in intensive care units: a Veterans
      Administration study.
AB  - OBJECTIVES: : To examine the effect of severity of acute kidney injury or renal
      recovery on risk-adjusted mortality across different intensive care unit
      settings. Acute kidney injury in intensive care unit patients is associated with
      significant mortality. DESIGN: : Retrospective observational study. SETTING: :
      There were 325,395 of 617,927 consecutive admissions to all 191 Veterans Affairs
      ICUs across the country. PATIENTS: : Large national cohort of patients admitted
      to Veterans Affairs ICUs and who developed acute kidney injury during their
      intensive care unit stay. MEASUREMENTS AND MAIN RESULTS: : Outcome measures were
      hospital mortality, and length of stay. Acute kidney injury was defined as a 0.3
      mg/dL increase in creatinine relative to intensive care unit admission and
      categorized into Stage I (0.3 mg/dL to <2 times increase), Stage II (> or =2 and
      <3 times increase), and Stage III (> or =3 times increase or dialysis
      requirement). Association of mortality and length of stay with acute kidney
      injury stages and renal recovery was examined. Overall, 22% (n = 71,486) of
      patients developed acute kidney injury (Stage I: 17.5%; Stage II: 2.4%; Stage
      III: 2%); 16.3% patients met acute kidney injury criteria within 48 hrs, with an
      additional 5.7% after 48 hrs of intensive care unit admission. Acute kidney
      injury frequency varied between 9% and 30% across intensive care unit admission
      diagnoses. After adjusting for severity of illness in a model that included urea
      and creatinine on admission, odds of death increased with increasing severity of
      acute kidney injury. Stage I odds ratio = 2.2 (95% confidence interval, 2.17
      2.30); Stage II odds ratio = 6.1 (95% confidence interval, 5.74, 6.44); and Stage
      III odds ratio = 8.6 (95% confidence interval, 8.07-9.15). Acute kidney injury
      patients with sustained elevation of creatinine experienced higher mortality risk
      than those who recovered. INTERVENTIONS: : None. CONCLUSIONS: : Admission
      diagnosis and severity of illness influence frequency and severity of acute
      kidney injury. Small elevations in creatinine in the intensive care unit are
      associated with increased risk-adjusted mortality across all intensive care unit
      settings, whereas renal recovery was associated with a protective effect.
      Strategies to prevent even mild acute kidney injury or promote renal recovery may
      improve survival.

PMID- 19602974
TI  - Gender impact on the outcomes of critically ill patients with nosocomial
      infections.
AB  - OBJECTIVES: : To investigate gender impact on the outcomes of severe nosocomial
      infections (pneumonia, bacteremia, catheter-related bloodstream infections,
      poststernotomy mediastinitis, urinary infections) occurring in a large cohort of
      patients hospitalized in a medical-surgical intensive care unit. Highly
      controversial data exist regarding gender-related differences in outcomes of
      severe nosocomial infections, reflecting potential confounders related to case
      mixes or heterogeneity of populations evaluated. DESIGN: : Retrospective study of
      patients admitted to our intensive care unit. Multivariable logistic regression
      analysis was used to control for confounders in the evaluation of gender impact
      on intensive care unit death post nosocomial infections. SETTING: : An 18-bed
      tertiary referral medical-surgical intensive care unit in a teaching hospital.
      PATIENTS: : Mixed population of patients who developed nosocomial infections in
      the intensive care unit. MEASUREMENTS AND MAIN RESULTS: : Among the 5081 patients
      admitted to our intensive care unit from 1995 to 2004, 1341 (34% women) developed
      nosocomial infections. Pneumonia and mediastinitis were more frequent in men (51%
      vs. 44%, p = .01 and 29% vs. 22%, p = .01, respectively) whereas urinary
      infections predominated for women (46% vs. 24%, p < .001). Durations of
      mechanical ventilation and intensive care unit stays and treatment intensity did
      not differ between genders. However, intensive care unit mortality was higher for
      women (37% vs. 32%, p = .06) and this excess mortality was statistically
      significant (odds ratio = 1.50, 95% Confidence Interval = 1.11-2.03), after
      controlling for other independent risk factors of intensive care unit death.
      Compared with those observed for men of the same subgroup, crude ICU death rates
      were significantly higher for women who developed pneumonia, who were <50 yrs old
      or had undergone heart surgery before intensive care unit admission. However,
      multivariable analyses retained feminine gender as significantly associated with
      mortality only for the last subgroup. CONCLUSIONS: : Female intensive care unit
      patients developing nosocomial infections seem to be at increased risk of
      intensive care unit mortality, after carefully controlling for other prognostic
      factors. Further studies are needed to elucidate the pathophysiology underlying
      this gender-related difference, to devise tailored gender-specific therapies that
      might improve outcomes.

PMID- 19602975
TI  - Randomized trial of light versus deep sedation on mental health after critical
      illness.
AB  - OBJECTIVES: : To investigate if light sedation favorably affects subsequent
      patient mental health compared with deep sedation. Symptoms of posttraumatic
      stress disorder are common in patients after they have undergone prolonged
      mechanical ventilation and are associated with sedation depth. DESIGN: :
      Randomized, open-label, controlled trial. SETTING: : Single tertiary care center.
      PATIENTS: : Adult patients requiring mechanical ventilation. INTERVENTIONS: :
      Patients were randomized to receive either light (patient awake and cooperative)
      or deep sedation (patient asleep, awakening upon physical stimulation).
      MEASUREMENTS AND MAIN RESULTS: : Self-reported measures of posttraumatic stress
      disorder, anxiety, and depression were collected at intensive care unit discharge
      and 4 wks later. The primary outcomes were symptoms of posttraumatic stress
      disorder, anxiety, and depression 4 wks after intensive care unit discharge.A
      total of 137 patients were assigned to either the light (n = 69) or the deep
      sedation (n = 68) group. Seven patients withdrew consent and one patient was
      randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in
      deep sedation) available for analysis. At the 4-wk follow-up, patients in the
      deep sedation group tended to have more posttraumatic stress disorder symptoms (p
      = .07); the deep sedation group had more trouble remembering the event (37% vs.
      14%; p = .02) and more disturbing memories of the intensive care unit (18% vs.
      4%; p = .05). Patients in the light sedation group had an average one day less
      being ventilated and 1.5 fewer days in the intensive care unit. There were no
      differences between the two groups in the occurrence of anxiety and depression,
      and also no difference in mortality or in the incidence of adverse events.
      CONCLUSIONS: : These data suggest that a strategy of light sedation affords
      benefits with regard to reduction of intensive care unit stay and duration of
      ventilation without negatively affecting subsequent patient mental health or
      patient safety.

PMID- 19602976
TI  - Decreasing pulmonary ventilation through bicarbonate ultrafiltration: an
      experimental study.
AB  - OBJECTIVE: : To demonstrate the technical feasibility of CO2 removal with a
      commercial hemofilter and a replacement solution containing sodium hydroxide to
      replace bicarbonate. DESIGN: : Prospective animal experiment in sheep. SUBJECTS:
      : Seven mixed-breed female sheep. INTERVENTIONS: : Blood ultrafiltrate containing
      half of the metabolic production of CO2 was removed with a commercial hemofilter
      and a replacement solution containing sodium hydroxide was given as replacement.
      Minute ventilation was lowered to less than half of its baseline value.
      Ultrafiltration was stopped at 18 hrs, and Paco2 was allowed to increase for
      about 1 hr; at this time, the sheep were electively killed. MEASUREMENTS AND MAIN
      RESULTS: : Every 6 hrs, blood was sampled from the carotid artery, the pulmonary
      artery, and from the extracorporeal perfusion circuit (before the hemofilter,
      immediately after the hemofilter, and after mixing with the replacement
      solution). To maintain normocapnia, minute ventilation was reduced from 3.8 +/-
      0.1 L/min to 1.9 +/- 0.7 L/min; Paco2 remained near constant during the study.
      The average blood pH, after mixing with the replacement solution, was 7.64 +/-
      0.12. One hour after the ultrafiltration had stopped, Paco2 had increased from
      36.7 +/- 4.2 torr (4.9 +/- 0.6 kPa) to 59.6 +/- 9 torr (7.9 +/- 1.2 kPa) (p <
      .01) and blood pH had decreased from 7.317 +/- 0.041 to 7.151 +/- 0.051 (p <
      .01). CONCLUSION: : CO2 removal with bicarbonate ultrafiltration may be an
      effective treatment for patients with respiratory failure.

PMID- 19602978
TI  - Current Opinion in Organ Transplantation. Editorial comment.

PMID- 19602979
TI  - Current Opinion in Organ Transplantation. Current world literature.

PMID- 19602981
TI  - The clustering of premature deaths in families.
AB  - BACKGROUND: Infant deaths cluster in families, but beyond infancy, little is
      known about familial aggregation of premature deaths. We hypothesized that an
      individual's risk of premature death would be influenced by prior premature
      deaths of any age in family members. METHODS: For all Danish residents registered
      in the Civil Registration System, 1968-2005, information was linked to the Causes
      of Death Register and the Danish Family Relation Database, yielding a cohort of
      4,870,821 persons linked to one or more relatives (93 million persons-years and
      73,278 deaths). We used log-linear Poisson regression to estimate mortality rate
      ratios (relative risks) for premature death (before age 40 years) in persons with
      a family history of premature death, compared with persons without such a
      history. RESULTS: Persons with a family history of premature death were 46% more
      likely themselves to die prematurely than persons without such a family history
      (relative risk [RR] = 1.46 [95% confidence interval = 1.42-1.50]). Relative risks
      were higher for concordant age at death, a close kinship relation, and similar
      causes of death. As expected, certain natural causes clustered among first-degree
      relatives (RRs ranged from 1.81-618), but unnatural causes of death, such as
      nonsimultaneous motor vehicle injuries, other injuries, and suicides, also
      clustered (RRs = 1.80, 3.53, and 4.23, respectively). Previous family history of
      premature death in a first-degree relative also increased the risk of dying from
      another cause (overall RR = 2.08 in infancy and 1.33 between ages 1 and 39).
      CONCLUSION: Premature deaths cluster in families, for both similar and dissimilar
      causes.

PMID- 19602980
TI  - Maternal body mass index and daughters' age at menarche.
AB  - BACKGROUND: The role of intergenerational influences on age at menarche has not
      been explored far beyond the association between mothers' and daughters'
      menarcheal ages. Small size at birth and childhood obesity have been associated
      with younger age at menarche, but the influence of maternal overweight or obesity
      on daughters' age at menarche has not been thoroughly examined. METHODS: In a
      follow-up study of the prospective Collaborative Perinatal Project, grown
      daughters were asked in 1987-1991 for their age at menarche. Data from the
      original Collaborative Perinatal Project (1959-1966) included their mothers'
      height and prepregnancy weight. In the follow-up study, 597 of 627 daughters had
      complete menarche and maternal data available and were included in the present
      analysis. We used polytomous logistic regression to examine the association
      between maternal overweight (body mass index [BMI] = 25-29.9 km/m) or obesity
      (BMI >or= 30) and daughter's age at menarche (<or=12, 12, 13, 14+ years).
      RESULTS: Compared with those whose mothers had a BMI less than 25, daughters of
      obese mothers experienced younger age at menarche (OR for menarche at <or=12
      years = 3.1 [1.1-9.2]). This association remained after adjusting for maternal
      age at menarche, maternal parity, socioeconomic status, race, and study site (OR
      = 3.3 [1.1-10.0]). Effect estimates for maternal overweight were close to the
      null. There was limited evidence of mediation by small for gestational age or BMI
      at age 7. CONCLUSIONS: Maternal obesity is associated with younger menarcheal age
      among daughters in this study, possibly via unmeasured shared factors.

PMID- 19602982
TI  - Artificial neural network versus multiple logistic function to predict 25-year
      coronary heart disease mortality in the Seven Countries Study.
AB  - AIMS AND METHODS: We investigated 12 763 men enrolled in the Seven Countries
      Study and 25-year coronary heart disease (CHD) mortality to compare the
      predictive discrimination of the multilayer perceptron (MLP) neural network
      versus multiple logistic function based on four standard, continuous risk
      factors, selected a priori. The patients were grouped according to geographical
      distribution, which also parallels CHD mortality risk. Logistic model solutions
      were estimated for each geographic area. Training neural network models were
      estimated in one high risk (US) and one low risk (Italy) population and each was
      rerun in each nonindex population. RESULTS: CHD mortality prediction by training
      MLP neural network or multiple logistic function had similar (0.669-0.699)
      receiver operating characteristic area under the curve (AUC). The rerun of MLP
      neural network models derived from the US and Italy yielded comparable AUC
      similar to the logistic solutions in Northern and Eastern Europe, but higher AUC
      in two areas [0.633 (logistic) vs. 0.665 or 0.666 (neural network: P<0.05) in
      Southern Europe and 0.676 (logistic) vs. 0.725 or 0.737 (neural network: P<0.01)
      in Japan]. CONCLUSION: This is the first investigation performed on
      epidemiological data to suggest a good performance in predicting long-term CHD
      mortality, on the basis of few continuous risk factors, of a training neural
      network model that could be rerun on different populations with satisfactory
      findings.

PMID- 19602983
TI  - Editorial: assessing MEG.

PMID- 19602984
TI  - American Clinical MEG Society (ACMEGS) position statement: the value of
      magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive
      presurgical evaluation of patients with medically intractable localization
      related epilepsy.

PMID- 19602985
TI  - A multistage system for the automated detection of epileptic seizures in neonatal
      electroencephalography.
AB  - This paper describes the design and test results of a three-stage automated
      system for neonatal EEG seizure detection. Stage I of the system is the initial
      detection stage and identifies overlapping 5-second segments of suspected seizure
      activity in each EEG channel. In stage II, the detected segments from stage I are
      spatiotemporally clustered to produce multichannel candidate seizures. In stage
      III, the candidate seizures are processed further using measures of quality and
      context-based rules to eliminate false candidates. False candidates because of
      artifacts and commonly occurring EEG background patterns such as bifrontal delta
      activity are also rejected. Seizures at least 10 seconds in duration are
      considered for reporting results. The testing data consisted of recordings of 28
      seizure subjects (34 hours of data) and 48 nonseizure subjects (87 hours of data)
      obtained in the neonatal intensive care unit. The data were not edited to remove
      artifacts and were identical in every way to data normally processed visually.
      The system was able to detect seizures of widely varying morphology with an
      average detection sensitivity of almost 80% and a subject sensitivity of 96%, in
      comparison with a team of clinical neurophysiologists who had scored the same
      recordings. The average false detection rate obtained in nonseizure subjects was
      0.74 per hour.

PMID- 19602986
TI  - Variability in the response to cyclooxygenase inhibitors: toward the
      individualization of nonsteroidal anti-inflammatory drug therapy.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain, inflammation, and
      fever by inhibiting cyclooxygenases (COXs). Nonsteroidal anti-inflammatory drugs
      selective for COX-2 were developed to inhibit the major enzymatic source of the
      prostaglandins that mediate pain and inflammation while sparing COX-1-derived
      prostaglandins that contribute dominantly to gastric cytoprotection. Indeed, such
      purpose-designed COX-2 inhibitors reduced the incidence of serious
      gastrointestinal adverse effects when compared with traditional NSAIDs; however,
      they confer a small but absolute cardiovascular hazard. The hazard might also
      extend to traditional NSAIDs, which are relatively selective for COX-2, such as
      diclofenac, meloxicam, and etodolac. The occurrence of complications and the
      therapeutic responses to individual NSAIDs may vary substantially from patient to
      patient. Exploitation of detectable variability in the biochemical response to
      NSAIDs may offer an approach to the personalization of the management of risk and
      benefit.

PMID- 19602987
TI  - Understanding FDA regulatory requirements for investigational new drug
      applications for sponsor-investigators.
AB  - Clinical investigators invoke a number of specific regulatory requirements if
      their study includes use of a pharmaceutical agent. Studies using a drug that has
      not been approved by the Food and Drug Administration (FDA) or for indications
      not in the approved labeling may require filing an Investigational New Drug (IND)
      application with the FDA. If a study meets specific regulatory exemption
      criteria, then an IND may not be needed. Individual investigators may meet the
      FDA definition of a sponsor-investigator, in which case the application process
      is generally less complicated than for commercial sponsors, and this review
      addresses only this circumstance. Filing an IND requires completion of 3 sets of
      forms: 1 detailing the study (FDA Form 1571), 1 providing information about the
      investigator and study site (FDA Form 1572), and 1 certifying that the study is
      registered in the national database of clinical trials (FDA Form 3674). If the
      IND is approved, the study may begin 30 days after the FDA acknowledges receipt
      and assigns an IND. If the FDA requires additional information or if the study is
      placed on a "clinical hold," the study must not proceed. While the IND is active,
      the investigator must also continue to meet a set of regulations for monitoring
      the study and reporting to the FDA.

PMID- 19602988
TI  - Early weight bearing after complete tibial shaft fractures in children.
AB  - This study determined the prevalence of complications related to early weight
      bearing and the factors associated with time to healing in children after a
      complete tibial shaft fracture. Radiographs and medical records were reviewed
      from patients with unilateral, closed, complete tibial shaft fractures who were
      treated nonoperatively with a long leg cast. There were 55 males (68.8%) and 25
      females (31.2%) with a mean +/- SD age of 6.0 +/- 4.0 years (range 1-16). There
      were few complications (2.5%) and patients healed faster if they bore weight
      earlier (0.3 days faster for each day earlier to weight bearing, P = 0.02), were
      younger (2.3 days faster per year younger, P < 0.001), were female (2.7 days
      faster than males, P = 0.02), or did not have a closed reduction (3.8 days
      faster, P = 0.002) (R = 0.63). Time to weight bearing after complete tibial shaft
      fracture was not associated with an increased risk of complications. Earlier
      weight bearing was associated with a shorter time to healing. This study provides
      support for treatment with early weight bearing in children with closed, complete
      tibial shaft fractures.

PMID- 19602990
TI  - Efficacy and tolerability of local estrogen therapy for urogenital atrophy.
AB  - OBJECTIVE: This study aimed to identify vaginal discomfort in the form of
      dryness, itching, burning, and dyspareunia, which remains an inadequately
      addressed clinical problem for many postmenopausal women, and to describe the age
      or menopause-related dysfunction of the female urethral tract, which is
      prevalent. METHODS: Medical literature on the incidence and treatment of
      vulvovaginal symptoms in postmenopausal women was reviewed. RESULTS: Urogenital
      atrophy should not be considered an inevitable consequence of menopause because
      various hormonal and nonhormonal products are available to relieve symptoms.
      Estrogen deficiency is the primary cause of atrophic urogenital changes, and
      postmenopausal estrogen therapy is the most logical choice for treatment. All
      available low-dose local estrogen formulations are effective, but the optimal
      dose and preferred mode of estrogen administration to achieve symptom relief can
      vary from woman to woman. Individualization of therapy is the key to balancing
      the desired local effects of topical vaginal estrogens with potential systemic
      effects, which may or may not be desired. CONCLUSIONS: This article reviews the
      use of products for the management of urogenital atrophy in terms of their
      efficacy, safety, and other characteristics that may influence prescribing and
      woman's preference.

PMID- 19602989
TI  - Sex steroid and tropic hormone levels may be associated with postoperative
      prognosis of vitrectomy in Korean postmenopausal women: a pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the postoperative prognostic
      value of sex hormones and related biochemical markers for vitrectomy in
      postmenopausal Korean women. METHODS: Twenty-three postmenopausal women
      undergoing vitrectomy who had not received hormone therapy were recruited. Before
      vitrectomy, hormonal profile such as follicle-stimulating hormone, estradiol,
      testosterone, tumor markers, and biochemical markers including homocysteine,
      glycosylated hemoglobin, protein, albumin, and lipid panel was measured. These
      parameters were correlated with ophthalmologic outcomes such as intraocular
      pressure, preoperative and postoperative visual acuity, and the visual
      improvement after surgery. RESULTS: Follicle-stimulating hormone showed a
      positive correlation with the logarithm of the minimal angle of resolution value
      of postoperative visual acuity (Pearson's correlation, 0.583; P = 0.009). This
      significance was maintained after age or preoperative visual acuity was adjusted
      (P = 0.006 and P = 0.013, respectively). Testosterone also showed a positive
      correlation with intraocular pressure before and after adjustment for age (P =
      0.027 and P = 0.033, respectively). CONCLUSIONS: Sex steroid and tropic hormones
      may be associated with postoperative ophthalmologic outcomes in the
      postmenopausal women undergoing vitrectomy. Further larger scale studies will be
      necessary to confirm these preliminary results.

PMID- 19602991
TI  - Biochemical markers for cardiovascular disease in recently postmenopausal women
      with or without hot flashes.
AB  - OBJECTIVE: Menopausal hot flashes may affect vascular function and perhaps
      explain conflicting data on cardiovascular disease (CVD) between observational
      and randomized hormone therapy (HT) studies. We prospectively assessed hot flash
      status in recently postmenopausal women and related it to a number of biochemical
      vascular surrogate markers for CVD. METHODS: Healthy, nonsmoking women (n = 150)
      exhibiting a broad range (no, mild, moderate, severe) of hot flashes and an onset
      of menopause within the previous 0.5 to 3 years were studied with laboratory
      tests for lipids, lipoproteins, apolipoproteins, high-sensitivity C-reactive
      protein, and sex hormone-binding globulin. RESULTS: Apart from marked differences
      in hot flashes, the groups showed comparable levels of estrone, estradiol, or
      free estradiol index. The levels of total cholesterol (3.7-9.1 mmol/L) were
      similar between the groups (P = 0.744), and hypercholesterolemia (>6.5 mmol/L)
      was encountered equally often (P = 0.699). No difference was seen in high-, low-,
      or very low-density lipoproteins, triglycerides, apolipoprotein A-1,
      apolipoprotein B (or their ratio), or lipoprotein(a) between the groups. The
      levels of sex hormone-binding globulin and high-sensitivity C-reactive protein
      correlated negatively with each other (r = -0.204; P = 0.013) but showed no
      dependence on hot flashes (P = 0.531 and P = 0.215, respectively). CONCLUSIONS:
      No baseline difference in lipid or nonlipid CVD risk factors was observed between
      women with hot flashes (potential HT users) and women with no or mild hot flashes
      (potential HT nonusers). This may imply that hot flash status per se cannot
      explain the difference between observational and randomized trials.

PMID- 19602992
TI  - Hypothermia increases interleukin-6 and interleukin-10 in juvenile endotoxemic
      mice.
AB  - OBJECTIVE: To develop a juvenile mouse model to establish effects of in vivo
      hypothermia on expression of the inflammation-modulating cytokines tumor necrosis
      factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10. Although
      induced hypothermia is neuroprotective in some patients, the mechanisms of
      protection are not well understood and concerns remain over potential detrimental
      effects, particularly in the setting of infection. We previously showed that in
      vitro hypothermia increases production of tumor necrosis factor-alpha and
      interleukin-1beta in lipopolysaccharide-treated monocytes. DESIGN: : Laboratory
      investigation. SETTING: Research laboratory. SUBJECTS: Juvenile (4-wk) male
      C57BL/6 mice. INTERVENTIONS: : Mice were given chlorpromazine to suspend
      thermoregulation and lipopolysaccharide to stimulate cytokine production. Core
      temperature was maintained at 32 degrees C or 37 degrees C for 6 hrs by adjusting
      environmental temperature. In separate experiments, lipopolysaccharide-treated
      mice were kept in a cooling chamber without chlorpromazine treatment.
      MEASUREMENTS AND MAIN RESULTS: Plasma and organs were collected for cytokine
      quantitation. Chlorpromazine-treated hypothermic mice had 2.3-fold and 1.8-fold
      higher plasma interleukin-6 and interleukin-10 levels at 6 hrs compared with
      identically treated normothermic mice (p < .05), whereas plasma tumor necrosis
      factor-alpha and interleukin-1beta were not significantly different at 2 hrs or 6
      hrs. Liver tumor necrosis factor-alpha and interleukin-6 were significantly
      higher in hypothermic vs. normothermic mice, but lung and brain cytokines were
      not different. Lipopolysaccharide-treated mice kept in a cooling chamber without
      chlorpromazine treatment developed varying degrees of hypothermia with associated
      increases in plasma interleukin-6 and interleukin-10. A nonspecific marker of
      stress (plasma corticosterone) was not affected by hypothermia in
      lipopolysaccharide-treated mice. CONCLUSION: Further studies are necessary to
      determine the mechanism and physiologic consequences of augmented systemic
      interleukin-6 and interleukin-10 expression during induced hypothermia.

PMID- 19602993
TI  - Early life events, sex, and arterial blood pressure in critically ill infants.
AB  - OBJECTIVE: To determine whether photo-protecting total parenteral nutrition in
      preterm infants influences arterial blood pressure differently according to
      gender. Blood pressure is influenced by complex mechanisms of vasomodulation.
      Oxidants are mediators and effectors in such reactions. Shielding total
      parenteral nutrition from light contributes to decrease the generation of
      peroxides. Girls may be better protected against an oxidant load than boys. We
      questioned whether shielding total parenteral nutrition may have cardiovascular
      effects that are influenced by gender. DESIGN: A post hoc subgroup analysis of
      the effect of shielding parenteral nutrition from light. SETTING: Neonatal
      intensive care unit. SUBJECTS: Preterm infants <1000 g with indwelling arterial
      catheters who received light exposed (n = 20) or light protected (n = 20)
      parenteral nutrition. INTERVENTIONS: Invasive monitoring, total parenteral
      nutrition. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure was recorded
      hourly and compared between light exposed and light protected over the first week
      of life; timed average maximum velocity (m/s) was measured in the superior
      mesenteric artery by Doppler; presence of ductus arteriosus was documented by
      cardiac ultrasound. Data were analyzed by analysis of variance. No differences
      were noted between light exposed and light protected in clinical determinants
      that may influence blood pressure. There was an interaction (p < .01) between
      gender and total parenteral nutrition on blood pressure. In girls (n = 17),
      systolic and diastolic blood pressures were higher (p < .01) and heart rate lower
      (p < .01) during light exposed. There was no effect on BP observed in boys (n =
      23). The linear correlation between timed average maximum velocity and systolic
      blood pressure was positive (p < .05). There was no echocardographic difference
      in hemodynamic variables between boys (n = 21) and girls (n = 9) who had a patent
      ductus. CONCLUSION: Failure to shield total parenteral nutrition from light
      results in higher blood pressure in a selected population of critically ill
      female infants. This information adds to our understanding of the multiple
      determinants involved in optimizing arterial blood pressure in a critical care
      environment.

PMID- 19602994
TI  - Management of hyperglycemia in the pediatric intensive care unit; implementation
      of a glucose control protocol.
AB  - OBJECTIVE: To evaluate a stepwise nurse-driven glucose control protocol for the
      treatment of hyperglycemia in critically ill pediatric patients. SETTING:
      Academic pediatric intensive care unit. DESIGN: Prospective observational study.
      PATIENTS: A total of 50 consecutively admitted critically ill children with
      hyperglycemia >8 mmol/L (>145 mg/dL) were included and treated according to the
      glucose control protocol. MEASUREMENTS AND MAIN RESULTS: Demographic data and
      clinical parameters were collected and different steps in the protocol were
      evaluated. Data were expressed as medians with interquartile ranges. Fifty
      children (28 boys), aged 3.5 yrs (range, 1.2 -9.3 yrs) were treated in 18 mos.
      Forty-two children had multiple organ failure. Eight children died. Insulin
      treatment was initiated 4 hrs after the first episode of hyperglycemia was
      documented (median blood glucose, 11.4 mmol/L, [207 mg/dL] [9.7-14.5 mmol/L, 176
      264 mg/dL]). Blood glucose was <8 mmol/L (<145 mg/dL) within 12 hrs of initiating
      insulin therapy in 47 (94%) of 50 children (median, 5 hrs). Duration of treatment
      was 34 hrs (17-72 hrs) and the maximum insulin dose ranged between 20 and 200
      mIU/kg/hr (median, 70 mIU/kg/hr). Episodes of severe hypoglycemia <2.2 mmol/L
      (<47 mg/dL) did not occur. CONCLUSION: The use of a stepwise nurse-driven glucose
      control protocol resulted in normoglycemia within 12 hrs for 94% of the children
      involved. Episodes of severe hypoglycemia did not occur. We conclude that the
      glucose control protocol is effective in treating hyperglycemia in critically ill
      children. Further studies are necessary to assess safety before the protocol
      could also be implemented in other pediatric intensive care units.

PMID- 19602995
TI  - Neurosurgical management of spinal dysraphism and neurogenic scoliosis.
AB  - STUDY DESIGN: To review diagnosis and treatment of neurogenic factors implicated
      in the development of progressive scoliosis. OBJECTIVE: Increased awareness of
      neurogenic causes as a contributing component of spinal cord tethering has led to
      enhanced radiographic surveillance for etiologic factors contributing to the
      genesis of scoliosis. Review of various manifestations of spinal dysraphism
      offers better definition of clinical indications for surveillance MRI scans and
      thus may contribute to improving outcomes for affected individuals. SUMMARY OF
      BACKGROUND DATA: Increasing utilization of surveillance MRI has led to a greater
      awareness of neurogenic causes as contributing factors in the setting of
      scoliosis. It is imperative for clinicians treating individuals with scoliosis to
      be aware of the most common etiologies of neurogenic factors as well as be
      cognizant of the neurosurgical approaches to treating these conditions in a pre
      emptive fashion. This will serve to minimize potential neurological complications
      and offer improved surgical outcomes after instrumentation. METHODS: Current
      therapeutic approaches were outlined for various etiologies of neurogenic
      scoliosis as well as neurosurgical management of the tethered cord, spinal cord
      tumors in addition to current challenges surrounding Chiari malformations and
      syringomyelia. RESULTS: Timely recognition of these frequently progressive
      conditions may not only prevent irreversible neurologic compromise but may also
      help to ameliorate or stabilize concurrent scoliosis. Tethered cords are best
      treated by releasing the affected cord and offers the best opportunity to
      stabilize or improve the scoliosis. Syringomyelia, often associated with a Chiari
      malformation, is a well-known progenitor of scoliosis, and addressing the
      underlying cause with a Chiari decompression frequently leads to a reduction or
      resolution of the syrinx and may result in a concomitant improvement in
      scoliosis. CONCLUSION: Surveillance MRI should be undertaken for scoliosis when
      there are clinical indications consistent for a tethered cord, spinal cord tumor,
      or Chiari malformation and associated syringomyelia.

PMID- 19602996
TI  - Rehabilitation after lumbar disc surgery: an update Cochrane review.
AB  - STUDY DESIGN: Cochrane systematic review of randomized controlled trials.
      OBJECTIVE: To evaluate the effects of active rehabilitation for adults after
      first-time lumbar disc surgery. SUMMARY OF BACKGROUND DATA: Several
      rehabilitation programs are available for individuals after lumbar disc surgery,
      however, little is known about the efficacy of these treatments. METHODS: Search
      strategies were performed on CENTRAL (The Cochrane Library 2007, Issue 2) and
      MEDLINE, EMBASE, CINAHL, and PsycINFO up to May 2007. All randomized controlled
      trials without language limitations were included. Pairs of review authors
      independently assessed studies for eligibility and risk of bias. A meta-analysis
      was performed with clinically homogeneous studies. The GRADE approach was used to
      determine the quality of evidence. RESULTS: Fourteen studies were included, 7 of
      which had a low risk of bias. Most programs were only assessed in 1 study.
      Statistical pooling was only completed for 3 comparisons in which exercises
      started 4 to 6 weeks postsurgery: exercise programs versus no treatment, high
      versus low intensity exercise programs, and supervised versus home exercises. We
      found low quality evidence (3 randomized controlled trials [RCTs], N = 122) that
      exercises are more effective than no treatment for pain at short-term follow-up
      (weighted mean difference [WMD]:-11.13; 95% CI: -18.44 to -3.82) and moderate
      evidence (2 RCTs, N = 102) that exercises are more effective for functional
      status on short-term follow-up (WMD: -6.50; 95% CI: -9.26 to -3.74). None of the
      studies reported that exercises increased the reoperation rate. We also found low
      quality evidence (2 RCTs, N = 103) that high intensity exercises are slightly
      more effective than low intensity exercise programs for pain in the short-term
      (WMD: -10.67; 95% CI: -17.04 to -4.30) and moderate evidence (2 RCTs, N = 103)
      that they are more effective for functional status in the short-term
      (standardized mean difference [SMD] -0.77; 95% CI: -1.17 to -0.36). Finally, we
      found low quality evidence (3 RCTs, N = 95) that there were no significant
      differences between supervised and home exercises for short-term pain relief
      (SMD: -1.12; 95% CI: -2.77-0.53) or functional status (3 RCT, N = 95; SMD -1.17;
      95% CI: -2.63-0.28). CONCLUSION: Exercise programs starting 4 to 6 weeks
      postsurgery seem to lead to a faster decrease in pain and disability than no
      treatment. High intensity exercise programs seem to lead to a faster decrease in
      pain and disability than low intensity programs. There were no significant
      differences between supervised and home exercises for pain relief, disability, or
      global perceived effect. There is no evidence that active programs increase the
      reoperation rate after first-time lumbar surgery.

PMID- 19602997
TI  - Congenital scoliosis: etiology and associations.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To provide a current overview of
      congenital scoliosis and associated conditions. SUMMARY OF BACKGROUND DATA: The
      etiology of congenital scoliosis is unknown. A variety of factors have been
      implicated in the development of vertebral abnormalities. These factors provide
      clues to the origin of congenital scoliosis. METHODS: A search of PubMed, using
      the keywords congenital scoliosis, etiology, and genetics was performed. RESULTS:
      Environmental factors, genetics, vitamin deficiency, chemicals, and drugs, singly
      or in combination, have all been implicated in the development of vertebral
      abnormalities. Whatever the cause, the physiologic injury occurs early in the
      embryologic period, well before the development of cartilage and bone. The
      resulting defects can lead to full or partial fusion or lack of development of
      the vertebrae, which, in turn, can cause a curvature that, may be progressive
      during the growth of the child. CONCLUSION: The origin of congenital scoliosis
      may be environmental, genetic, or a combination of factors. Research on these
      various factors continues. Early identification and management of concomitant
      defects can improve the patient's quality of life.

PMID- 19602998
TI  - Pre-existing immunity and passive immunity to adenovirus 5 prevents toxicity
      caused by an oncolytic adenovirus vector in the Syrian hamster model.
AB  - We have used Syrian hamsters to examine the role of pre-existing immunity to
      adenovirus (Ad) 5 in the toxicity of the oncolytic Ad vector INGN 007. Groups of
      hamsters were or were not immunized with Ad5. Half the hamsters were
      immunosuppressed using cyclophosphamide (CP), then injected intravenously (i.v.)
      with 3x the maximum tolerated dose (MTD) of INGN 007 (in immunocompetent
      hamsters), and toxicity and vector replication in the liver were quantitated. In
      nonimmunized immunocompetent hamsters, toxicity was observed early but the
      hamsters recovered by day 6 after vector injection. In nonimmunized
      immunosuppressed hamsters, the vector was lethal by 3 days. Pre-existing
      neutralizing antibody (NAb) prevented liver infection and hepatotoxicity in both
      immunocompetent and immunosuppressed hamsters. In another study, passive
      immunization of immunosuppressed hamsters 1 day before a lethal dose (1x MTD) of
      INGN 007 prevented liver infection and replication, but immunization 1 day after
      vector administration was barely effective. When immunosuppressed hamsters were
      passively immunized 1 day after injection of 1/3rd the MTD of INGN 007, then
      significant protection was observed against liver infection and toxicity.
      Therefore, serum NAb are sufficient to prevent oncolytic Ad vector liver
      infection and toxicity. We saw no evidence that pre-existing immunity was
      associated with increased vector toxicity.

PMID- 19602999
TI  - Allogeneic mesenchymal stem cells for treatment of experimental autoimmune
      encephalomyelitis.
AB  - The use of allogeneic "universal donor" mesenchymal stromal cells (MSCs) may be a
      substantial clinical convenience for treatment of autoimmune ailments such as
      multiple sclerosis. We therefore tested whether allogeneic MSCs can be exploited
      for treatment of experimental autoimmune encephalomyelitis (EAE) in mice with
      otherwise intact immune system. Administration of allogeneic Balb/c-derived MSCs
      to C57Bl/6 mice with pre-established EAE led to a significant decrease in disease
      score over time comparable to that achieved with syngeneic MSCs, and was
      correlated with a significant blunting of immune cell infiltration to the spinal
      cord and reduced circulating levels of interferon-gamma (IFN-gamma) and
      interleukin-17. Pretreatment of allogeneic MSCs with IFN-gamma increased the
      expression levels of CCL2 as well as major histocompatibility complex I (MHCI)
      and MHCII, but also led to complete loss of suppressive activity in vivo that
      correlated with immune rejection. In conclusion, allogeneic MSCs can suppress the
      manifestations of EAE, yet retain the potential for alloimmunization.

PMID- 19603000
TI  - Influence of coagulation factor x on in vitro and in vivo gene delivery by
      adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors.
AB  - The binding of coagulation factor X (FX) to the hexon of adenovirus (Ad) 5 is
      pivotal for hepatocyte transduction. However, vectors based on Ad35, a subspecies
      B Ad, are in development for cancer gene therapy, as Ad35 utilizes CD46 (which is
      upregulated in many cancers) for transduction. We investigated whether
      interaction of Ad35 with FX influenced vector tropism using Ad5, Ad35, and
      Ad5/Ad35 chimeras: Ad5/fiber(f)35, Ad5/penton(p)35/f35, and Ad35/f5. Surface
      plasmon resonance (SPR) revealed that Ad35 and Ad35/f5 bound FX with
      approximately tenfold lower affinities than Ad5 hexon-containing viruses, and
      electron cryomicroscopy (cryo-EM) demonstrated a direct Ad35 hexon:FX
      interaction. The presence of physiological levels of FX significantly inhibited
      transduction of vectors containing Ad35 fibers (Ad5/f35, Ad5/p35/f35, and Ad35)
      in CD46-positive cells. Vectors were intravenously administered to CD46
      transgenic mice in the presence and absence of FX-binding protein (X-bp),
      resulting in reduced liver accumulation for all vectors. Moreover, Ad5/f35 and
      Ad5/p35/f35 efficiently accumulated in the lung, whereas Ad5 demonstrated poor
      lung targeting. Additionally, X-bp significantly reduced lung genome accumulation
      for Ad5/f35 and Ad5/p35/f35, whereas Ad35 was significantly enhanced. In summary,
      vectors based on the full Ad35 serotype will be useful vectors for selective gene
      transfer via CD46 due to a weaker FX interaction compared to Ad5.

PMID- 19603001
TI  - Impact of the underlying mutation and the route of vector administration on
      immune responses to factor IX in gene therapy for hemophilia B.
AB  - Immune responses to factor IX (F.IX), a major concern in gene therapy for
      hemophilia, were analyzed for adeno-associated viral (AAV-2) gene transfer to
      skeletal muscle and liver as a function of the F9 underlying mutation. Vectors
      identical to those recently used in clinical trials were administered to four
      lines of hemophilia B mice on a defined genetic background [C3H/HeJ with deletion
      of endogenous F9 and transgenic for a range of nonfunctional human F.IX (hF.IX)
      variants]. The strength of the immune response to AAV-encoded F.IX inversely
      correlated with the degree of conservation of endogenous coding information and
      levels of endogenous antigen. Null mutation animals developed T- and B-cell
      responses in both protocols. However, inhibitor titers were considerably higher
      upon muscle gene transfer (or protein therapy). Transduced muscles of Null mice
      had strong infiltrates with CD8+ cells, which were much more limited in the liver
      and not seen for the other mutations. Sustained expression was achieved with
      liver transduction in mice with crm(-) nonsense and missense mutations, although
      they still formed antibodies upon muscle gene transfer. Therefore, endogenous
      expression prevented T-cell responses more effectively than antibody formation,
      and immune responses varied substantially depending on the protocol and the
      underlying mutation.

PMID- 19603002
TI  - Generation of novel AAV variants by directed evolution for improved CFTR delivery
      to human ciliated airway epithelium.
AB  - Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to
      the airway epithelium of cystic fibrosis (CF) patients. However, no significant
      CFTR function has been demonstrated likely due to low transduction efficiencies
      of the AAV vectors. To improve AAV transduction efficiency for human airway
      epithelium (HAE), we generated a chimeric AAV library and performed directed
      evolution of AAV on an in vitro model of human ciliated airway epithelium. Two
      independent and novel AAV variants were identified that contained capsid
      components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the
      two novel AAV variants for human ciliated airway epithelium were three times
      higher than that for AAV-6. The novel variants were then used to deliver CFTR to
      ciliated airway epithelium from CF patients. Here we show that our novel AAV
      variants, but not the parental, AAV provide sufficient CFTR delivery to correct
      the chloride ion transport defect to ~25% levels measured in non-CF cells. These
      results suggest that directed evolution of AAV on relevant in vitro models will
      enable further improvements in CFTR gene transfer efficiency and the development
      of an efficacious and safe gene transfer vector for CF lung disease.

PMID- 19603003
TI  - Vesicular stomatitis virus as a novel cancer vaccine vector to prime antitumor
      immunity amenable to rapid boosting with adenovirus.
AB  - Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for
      immunization against viral infection, but its potential to induce an immune
      response to a self-tumor antigen has not been investigated. We constructed a
      recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its
      immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT
      activated both CD4(+) and CD8(+) DCT-specific T-cell responses. The magnitude of
      these responses could be significantly increased by booster immunization with
      recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10
      melanoma in both prophylactic and therapeutic settings. Notably, the interval of
      VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it
      a potential regimen to rapidly expand antigen-specific effector cells.
      Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad
      hDCT, suggesting VSV is efficient for both priming and boosting of the immune
      response against a self-tumor antigen.

PMID- 19603004
TI  - Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic
      skeletal muscle.
AB  - We have isolated a population of muscle-derived stem cells (MDSCs) that, when
      compared with myoblasts, display an improved regeneration capacity, exhibit
      better cell survival, and improve myogenesis and angiogenesis. In addition, we
      and others have observed that the origin of the MDSCs may reside within the blood
      vessel walls (endothelial cells and pericytes). Here, we investigated the role of
      vascular endothelial growth factor (VEGF)-mediated angiogenesis in MDSC
      transplantation-based skeletal muscle regeneration in mdx mice (an animal model
      of muscular dystrophy). We studied MDSC and MDSC transduced to overexpress VEGF;
      no differences were observed in vitro in terms of phenotype or myogenic
      differentiation. However, after in vivo transplantation, we observe an increase
      in angiogenesis and endogenous muscle regeneration as well as a reduction in
      muscle fibrosis in muscles transplanted with VEGF-expressing cells when compared
      to control cells. In contrast, we observe a significant decrease in
      vascularization and an increase in fibrosis in the muscles transplanted with
      MDSCs expressing soluble forms-like tyrosine kinase 1 (sFlt1) (VEGF-specific
      antagonist) when compared to control MDSCs. Our results indicate that VEGF
      expressing cells do not increase the number of dystrophin-positive fibers in the
      injected mdx muscle, when compared to the control MDSCs. Together the results
      suggest that the transplantation of VEGF-expressing MDSCs improved skeletal
      muscle repair through modulation of angiogenesis, regeneration and fibrosis in
      the injected mdx skeletal muscle.

PMID- 19603005
TI  - Determination of the fate and contribution of ex vivo expanded human bone marrow
      stem and progenitor cells for bone formation by 2.3ColGFP.
AB  - Bone marrow transplantation can provide an effective cell-based strategy to
      enhance bone repair. However, the fate of implanted cells and the extent of their
      contribution to bone osteoinduction remain uncertain. To define the fate of bone
      marrow-derived cells and their contribution in vivo, we used a bone-specific
      collagen I promoter (2.3Col) driving green fluorescent protein (GFP) (2.3ColGFP)
      within a lentiviral vector. Prior to in vivo cell fate determination, we verified
      a high efficiency of lentiviral transduction in human bone marrow stromal cells
      (hBMSCs), without altering the proliferation or differentiation potential of
      these cells. We showed that the 2.3ColGFP marker responded to endogenous
      transcriptional regulation signals. In a mouse ossicle model, we demonstrated
      that the 2.3ColGFP marker is able to specifically define human bone marrow
      derived stem cells that enter the osteoblast lineage in vivo. In addition, cells
      labeled with 2.3ColGFP with the donor origin, directly make a major contribution
      to bone formation. Furthermore, we also demonstrated in a calvarial defect model
      that a mixture of human bone marrow-derived populations, have stronger bone
      regenerative potential than that of hBMSCs, and an optimal dose is required for
      bone regeneration by the mixed populations.

PMID- 19603006
TI  - Transplantation of mesenchymal stem cells overexpressing RANK-Fc or CXCR4
      prevents bone loss in ovariectomized mice.
AB  - Osteoporosis is a systemic skeletal disorder characterized by reduced bone
      mineral density (BMD) and increased risk of fracture. We studied the effects of
      transplantation of mesenchymal stem cells (MSCs) overexpressing receptor
      activator of nuclear factor-kappaB (RANK)-Fc and CXC chemokine receptor-4 (CXCR4)
      using retrovirus on ovariectomy (OVX)-induced bone loss in mice. Ten-week-old
      adult female C57BL/6 mice were divided into six groups as follows: Sham-operated
      mice treated with phosphate-buffered saline (PBS) (Sham-op + PBS); OVX mice
      intravenously transplanted with syngeneic MSCs overexpressing RANK-Fc-DsRED and
      CXCR4-GFP (RANK-Fc + CXCR4); RANK-Fc-DsRED and GFP (RANK-Fc + GFP); CXCR4-GFP and
      DsRED (CXCR4 + RED); DsRED and GFP (RED + GFP); or treated with PBS only (OVX +
      PBS). Measurement of BMD showed that introduction of RANK-Fc resulted in
      significant protection against OVX-induced bone loss compared to treatment with
      PBS (-0.1% versus -6.2%, P < 0.05) at 8 weeks after cell infusion. CXCR4 + RED
      group also significantly prevented bone loss compared to OVX + PBS group (2.7%
      versus -6.2%, P < 0.05). Notably, the effect of RANK-Fc + CXCR4 was greater than
      that of RANK-Fc + GFP (4.4% versus -0.1%, P < 0.05) while it was not
      significantly different from that in CXCR4 + RFP group (4.4% versus 2.7%, P =
      0.055) at 8 weeks. Transplantation of MSCs with control virus (RED + GFP group)
      also resulted in amelioration of bone loss compared to OVX + PBS group (-1.7%
      versus -6.2%, P < 0.05). Fluorescence-activated cell sorting (FACS) and real-time
      quantitative PCR (qPCR) analysis for GFP from bone tissue revealed enhanced cell
      trafficking to bone by co-overexpression of CXCR4. In conclusion, we have
      demonstrated that intravenous transplantation of syngeneic MSCs overexpressing
      CXCR4 could promote increased in vivo cell trafficking to bone in OVX mice, which
      could in itself protect against bone loss but also enhance the therapeutic
      effects of RANK-Fc.

PMID- 19603007
TI  - Conditions for tumor-free and dopamine neuron-enriched grafts after transplanting
      human ES cell-derived neural precursor cells.
AB  - We have previously demonstrated derivation of neural precursor (NP) cells of a
      midbrain-type from human embryonic stem (hES) cells to yield an enriched
      population of dopamine (DA) neurons. These hES-derived NPs can be expanded in
      vitro through multiple passages without altering their DA neurogenic potential.
      Here, we studied two aspects of these hES-NP cells that are critical issues in
      cell therapeutic approaches for Parkinson's disease (PD): cell survival and
      tumorigenic potential. Neuroepithelial rosettes, a potentially tumorigenic
      structure, disappeared during hES-NP cell expansion in vitro. Although a minor
      population of cells positive for Oct3/4, a marker specific for undifferentiated
      hES cells, persisted in culture during hES-NP cell expansion, they could be
      completely eliminated by subculturing hES-NPs under differentiation-inducing
      conditions. Consistently, no tumors/teratomas are formed in rats grafted with
      multipassaged hES-NPs. However, extensively expanded hES-NP cells easily
      underwent cell death during differentiation in vitro and after transplantation in
      vivo. Transgenic expression of Bcl-XL and sonic hedgehog (SHH) completely
      overcame the cell survival problems without increasing tumor formation. These
      findings indicate that hES-NP cell expansion in conjunction with Bcl-XL+SHH
      transgene expression may provide a renewable and safe source of DA neurons for
      transplantation in PD.

PMID- 19603008
TI  - Definition and implications of novel pharyngo-glottal reflex in human infants
      using concurrent manometry ultrasonography.
AB  - OBJECTIVES: Glottal relationships during swallowing dominate the etiology of
      dysphagia. We investigated the pharyngo-glottal relationships during basal and
      adaptive swallowing. METHODS: Temporal changes in glottal closure kinetics
      (frequency, response latency, and duration) with spontaneous and adaptive
      pharyngeal swallows were defined in 12 infants using concurrent
      pharyngoesophageal manometry and ultrasonography of the glottis. RESULTS:
      Frequency, response latency, and duration of glottal closure with spontaneous
      swallows (n=53) were 100%, 0.27+/-0.1 s, and 1+/-0.22 s, respectively. The
      glottis adducted earlier (P<0.0001 vs. upper esophageal sphincter relaxation)
      within the same respiratory phase as swallow (P=0.03). With pharyngeal
      provocations (n=41), glottal adduction (pharyngo-glottal closure reflex (PGCR))
      was noted first and then again with pharyngeal reflexive swallow (PRS). The
      frequency, response latency, and duration of glottal closure with PGCR were 100%,
      0.56+/-0.13 s, and 0.52+/-0.1 s, respectively. Response latency to PRS was 3.24+/
      0.33 s; the glottis adducted 97% within 0.36+/-0.08 s in the same respiratory
      phase (P=0.03), and remained adducted for 3.08+/-0.71 s. Glottal adduction was
      the quickest with spontaneous swallow (P=0.04 vs. PGCR), and the duration was the
      longest during PRS (P<0.005 vs. PGCR or spontaneous swallow). CONCLUSIONS:
      Glottal adduction during basal or adaptive swallowing reflexes occurs in either
      respiratory phase, thus ensuring airway protection against pre-deglutitive or
      deglutitive aspiration. The independent existence and magnitude (duration of
      adduction) of PGCR suggests a hypervigilant state of the glottis in preventing
      aspiration during swallowing or during high gastroesophageal reflux events.
      Investigation of pharyngeal-glottal relationships with the use of noninvasive
      methods may be more acceptable across the age spectrum.

PMID- 19603009
TI  - Repeat radiofrequency ablation provides survival benefit in patients with
      intrahepatic distant recurrence of hepatocellular carcinoma.
AB  - OBJECTIVES: Intrahepatic distant recurrence (IDR) of hepatocellular carcinoma
      (HCC) after curative treatment occurs frequently and influences the prognoses.
      The aim of this study was to determine prognostic factors affecting survival
      after IDR and the optimum therapy for IDR. METHODS: A total of 115 patients with
      a single small primary HCC who had complete radiofrequency (RF) ablation were
      enrolled in this study. The prognostic factors and the optimum therapy affecting
      survival were statistically analyzed among patients with IDRs. RESULTS: IDRs were
      observed in 59 (51.3%) patients with the median observation period of 19.6
      months. The cumulative rates of IDRs were 11.8, 53.9, and 75.8% at 1, 3, and 5
      years, respectively. IDR nodules were present as a single nodule in 38 patients
      and as multiple nodules in 21 patients. In all, 23 patients died during the
      follow-up. A total of 30 patients were treated with RF ablation, and 27 were
      treated with transcatheter arterial chemoembolization (TACE). The overall
      cumulative survival rates after IDRs were 92.7, 55.4, and 43.7% at 1, 3, and 5
      years, respectively. A multivariate analysis showed that treatment with RF
      ablation for IDR was a significant favorable prognostic factor after IDR (hazard
      ratio: 0.167, 95% confidence interval: 0.048-0.584, P=0.005). In a comparison of
      survival after IDR between patients treated with RF ablation and TACE, who were
      comparable with clinical and tumoral characteristics, the cumulative survival
      rate of patients treated with RF ablation was significantly higher than that of
      those treated with TACE (77.2 vs 28.5% at 3 years). The cumulative survival rates
      obtained from the initial RF ablation of the patients with IDRs treated with
      repeat RF ablation were similar to those of recurrence-free patients.
      CONCLUSIONS: Repeat RF ablation should be attempted for IDR as much as possible
      despite tumor multiplicity for survival benefit; by reducing the need, it will
      help solve the problem of the current shortage of donors for liver
      transplantations.

PMID- 19603011
TI  - Natural history of acute pancreatitis: a long-term population-based study.
AB  - OBJECTIVES: It is unknown whether after an initial attack of acute pancreatitis,
      the inflamed gland heals completely, or whether and under what circumstances the
      disease progresses to chronic pancreatitis. Therefore, the aim of this study was
      to investigate the progression of disease from acute to chronic pancreatitis.
      METHODS: During a 20-year period, 532 patients who were hospitalized after an
      initial attack of acute pancreatitis were followed up for an average of 7.8 years
      (range: 1 day to 19.7 years). We used the Kaplan-Meier method to study the
      frequency of recurrent attacks of pancreatitis, subsequent development of chronic
      pancreatitis, and all-cause mortality during the follow-up period in patients
      with pancreatitis due to different causes. RESULTS: During the follow-up period,
      recurrent pancreatitis developed in 88 (16.5%) patients. The annual relapse rates
      were 5.3, 1.5, 0.6, and 1.9/100 per year in patients with acute pancreatitis due
      to alcohol, gallstones (biliary), and other identified causes of unknown origin
      (idiopathic), respectively. Chronic pancreatitis developed only in alcoholics,
      independent of the severity of the first attack and also of discontinuation of
      alcohol and nicotine consumption. The cumulative incidence of chronic
      pancreatitis was 13% in 10 years and 16% in 20 years. After surviving a second
      attack, the incidence of chronic pancreatitis increased distinctly to 38% after
      only 2 years of follow-up. Smoking significantly enhanced the risk of progression
      from acute to chronic alcoholic pancreatitis. CONCLUSIONS: The progression from
      acute to chronic pancreatitis occurred only in alcoholics. In this group, a
      substantial number of patients developed chronic pancreatitis in a short period
      of time after surviving a second attack of acute pancreatitis. Both alcohol
      consumption and smoking at this time are risk factors for the transition from
      acute to chronic pancreatitis.

PMID- 19603010
TI  - Genotypic and functional roles of IL-1B and IL-1RN on the risk of
      gastroesophageal reflux disease: the presence of IL-1B-511*T/IL-1RN*1 (T1)
      haplotype may protect against the disease.
AB  - OBJECTIVES: We aimed at evaluating the role of interleukin-1B (IL-1B) and IL-1RN
      polymorphisms, which may modulate the gastric mucosal expression of IL-1beta,
      thus altering acid secretion, which influences the severity of gastroesphageal
      reflux disease (GERD). METHODS: In a prospective study, 144 patients with GERD
      (diagnosed by at least two of these criteria: Carlsson-Dent score of 6,
      endoscopic evidence of GERD, histopathological evidence of esophagitis,
      percentage time esophageal pH <4 for >5% on 24-h pH monitoring, and response to
      omeprazole 20 mg/day) and 368 healthy controls were genotyped for IL-1B-511 C/T
      and IL-1RN VNTR polymorphism (by PCR-restriction fragment length polymorphism
      (RFLP) and PCR, respectively). Gastric mucosal IL-1beta levels
      (picogram/milligram of biopsy sample) were measured (using enzyme-linked
      immunosorbent assay (ELISA)) in 71 patients. Helicobacter pylori diagnosis was
      conducted using anti-H. pylori immunoglobulin G (IgG) ELISA. RESULTS: Patients
      (41.1+/-13.3 years old, 96 (66.7%) men) were comparable with healthy controls
      (43.4+/-11.8 years old, 238 (64.7%) men) with respect to age and gender. The IL
      1B-511 CC genotype and C allele were associated with higher risk of GERD than the
      TT genotype (P=0.01, odds ratio (OR)=2.0, 95% confidence interval (CI)=1.12-3.57)
      and the T allele (P=0.04, OR=1.3, 95% CI=1.0-1.7), respectively. TT and C
      noncarriers had more IL-1beta than CT (33.2 (2.6-161.3) vs. 16.7 (2.8-121.9),
      P=0.04) and C carriers (33.2 (2.6-161.3) vs. 15.16 (1.5-121.9), P=0.04),
      respectively. IL-1RN "1,2" and "2 carriers" had higher risk (P<0.001, OR=2.0, 95%
      CI=1.31-3.1; P=0.01, OR=1.6, 95% CI=1.1-2.4, respectively). "2,2" Had lower IL
      1beta levels than both "1,1" and "1,2" (9.2 (1.5-70.7) vs. 26.8 (5.7-161.3),
      P=0.006; 9.2 (1.5-70.7) vs. 24.4 (2.6-78.0), P=0.02). However, "2 carriers"
      tended to have lower IL-1beta levels than "2 noncarriers" (21.7 (1.5-78.0) vs.
      26.8 (5.7-161.3), P=0.09). The IL-1B-511*T/IL-1RN*1 ("T1") haplotype showed lower
      risk (P=0.05, OR=0.7, 95% CI=0.5-1.0). "T1" had higher IL-1beta levels than both
      "T1 carriers" and "T1 noncarriers" (43.5 (18.2-161.3) vs. 23.9 (2.6-121.9),
      P=0.02; 43.5 (18.2-161.3) vs. 10.9 (1.5-82.6), P=0.06, respectively). The
      presence of H. pylori infection was associated with the stronger risk of the IL
      1B-511*CC genotype. The "T1" haplotype was strongly protective against GERD among
      patients with H. pylori infection. CONCLUSIONS: The T1 haplotype was associated
      with the reduced risk of GERD, particularly among patients with H. pylori
      infection, probably because of higher gastric mucosal IL-1beta levels.

PMID- 19603012
TI  - Laboratory tests for patients with ileal pouch-anal anastomosis: clinical utility
      in predicting, diagnosing, and monitoring pouch disorders.
AB  - Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the
      surgical treatment of choice for patients with medically refractory ulcerative
      colitis (UC) or UC-associated dysplasia, and for the majority of patients with
      familial adenomatous polyposis. Pouchitis and other complications of IPAA are
      common. There are scant data on laboratory markers for the evaluation and
      diagnosis of pouch disorders. The presence of immunogenotypic markers such as
      genetic polymorphisms of interleukin-1 (IL-1) receptor antagonist, NOD2/CARD15,
      Toll-like receptor, and tumor necrosis factor-alpha has been reported to be
      associated with pouchitis. Immunophenotypic/serologic markers such as perinuclear
      antineutrophil cytoplasmic antibody and anti-CBir1 have been investigated as
      possible markers for predicting and diagnosing pouchitis. Fecal markers including
      lactoferrin and calprotectin seem to be useful in distinguishing inflammatory
      from noninflammatory pouch disorders. In our practice, we have encountered a
      large number of pouch patients with Clostridium difficile infection. Laboratory
      evaluation provides information on the etiology and pathogenesis of pouchitis,
      and it also helps practicing clinicians with accurate diagnosis, differential
      diagnosis, disease stratification, and management of ileal pouch disorders.

PMID- 19603013
TI  - Newly characterised ex vivo colospheres as a three-dimensional colon cancer cell
      model of tumour aggressiveness.
AB  - BACKGROUND: New models continue to be required to improve our understanding of
      colorectal cancer progression. To this aim, we characterised in this study a
      three-dimensional multicellular tumour model that we named colospheres, directly
      obtained from mechanically dissociated colonic primary tumours and correlated
      with metastatic potential. METHODS: Colorectal primary tumours (n=203) and 120
      paired non-tumoral colon mucosa were mechanically disaggregated into small
      fragments for short-term cultures. Features of tumours producing colospheres were
      analysed. Further characterisation was performed using colospheres, generated
      from a human colon cancer xenograft, and spheroids, formed on agarose by the
      paired cancer cell lines. RESULTS: Colospheres, exclusively formed by viable
      cancer cells, were obtained in only 1 day from 98 tumours (47%). Inversely, non
      tumoral colonic mucosa never generated colospheres. Colosphere-forming capacity
      was statistically significantly associated with tumour aggressiveness, according
      to AJCC stage analysis. Despite a close morphology, colospheres displayed higher
      invasivity than did spheroids. Spheroids and colospheres migrated into Matrigel
      but matrix metalloproteinase (MMP)-2 and MMP-9 activity was detected only in
      colospheres. Mouse subrenal capsule assay revealed the unique tumorigenic and
      metastatic phenotype of colospheres. Moreover, colospheres and parental xenograft
      reproduced similar CD44 and CD133 expressions in which CD44+ cells represented a
      minority subset of the CD133+ population. CONCLUSION: The present colospheres
      provide an ex vivo three-dimensional model, potentially useful for studying
      metastatic process.

PMID- 19603014
TI  - Activated 4E-BP1 represses tumourigenesis and IGF-I-mediated activation of the
      eIF4F complex in mesothelioma.
AB  - BACKGROUND: Insulin-like growth factor (IGF)-I signalling stimulates
      proliferation, survival, and invasion in malignant mesothelioma and other tumour
      types. Studies have found that tumourigenesis is linked to dysregulation of cap
      dependent protein translation. METHODS: The effect of IGF stimulation on cap
      mediated translation activation in mesothelioma cell lines was studied using
      binding assays to a synthetic 7-methyl GTP-cap analogue. In addition, cap
      mediated translation was genetically repressed in these cells with a dominant
      active motive of 4E-BP1. RESULTS: In most mesothelioma cell lines, IGF-I
      stimulation resulted in a hyperphosphorylation-mediated inactivation of 4E-BP1
      compared with that in normal mesothelial cells. An inhibitor of Akt diminished
      IGF-I-mediated phosphorylation of 4E-BP1, whereas inhibiting MAPK signalling had
      no such effect. IGF-I stimulation resulted in the activation of the cap-mediated
      translation complex as indicated by an increased eIF4G/eIF4E ratio in cap
      affinity assays. Akt inhibition reversed the eIF4G/eIF4E ratio. Mesothelioma
      cells transfected with an activated 4E-BP1 protein (4E-BP1(A37/A46)) were
      resistant to IGF-I-mediated growth, motility, and colony formation. In a murine
      xenograft model, mesothelioma cells expressing the dominant active 4E
      BP1(A37/A46) repressor protein showed abrogated tumourigenicity compared with
      control tumours. CONCLUSION: IGF-I signalling in mesothelioma cells drives cell
      proliferation, motility, and tumourigenesis through its ability to activate cap
      mediated protein translation complex through PI3K/Akt/mTOR signalling.

PMID- 19603015
TI  - Current strategies for monitoring men with localised prostate cancer lack a
      strong evidence base: observational longitudinal study.
AB  - BACKGROUND: The UK National Institute for Health and Clinical Excellence (NICE)
      guidance recommends conservative management of men with 'low-risk' localised
      prostate cancer, monitoring the disease using prostate-specific antigen (PSA)
      kinetics and re-biopsy. However, there is little evidence of the changes in PSA
      level that should alert to the need for clinical re-assessment. METHODS: This
      study compares the alerts resulting from PSA kinetics and a novel longitudinal
      reference range approach, which incorporates age-related changes, during the
      monitoring of 408 men with localised prostate cancer. Men were monitored by
      regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling
      time fell below 2 years, PSA velocity exceeded 2 ng ml(-1) per year, or when his
      upper 10% reference range was exceeded. RESULTS: Prostate-specific antigen
      doubling time and PSA velocity alerted a high proportion of men initially but
      became unresponsive to changes with successive tests. Calculating doubling time
      using recent PSA measurements reduced the decline in response. The reference
      range method maintained responsiveness to changes in PSA level throughout the
      monitoring. CONCLUSION: The increasing unresponsiveness of PSA kinetics is a
      consequence of the underlying regression model. Novel methods are needed for
      evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE
      guidance should be cautious.

PMID- 19603016
TI  - Clinical outcome data for symptomatic breast cancer: the Breast Cancer Clinical
      Outcome Measures (BCCOM) Project.
AB  - BACKGROUND: Data collection for screen-detected breast cancer in the United
      Kingdom is fully funded, which has led to improvements in clinical practice.
      However, data on symptomatic cancer are deficient, and the aim of this project
      was to monitor the current practice. METHODS: A data set was designed together
      with surrogate outcome measures to reflect best practice. Data from cancer
      registries initially required the consent of clinicians, but in the third year
      anonymised data were available. RESULTS: The quality of data improved, but this
      varied by region and only a third of the cases were validated by clinicians.
      Regional variations in mastectomy rates were identified, and one-third of
      patients who underwent conservative surgery for the treatment invasive breast
      cancer were not recorded as receiving radiotherapy. CONCLUSION: National data are
      essential to ensure that all patients receive appropriate treatment for breast
      cancer, but variations still exist in the United Kingdom and further improvement
      in data capture is required.

PMID- 19603017
TI  - Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance
      proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression.
AB  - BACKGROUND: Invasion and metastases of cancer cells and the development of
      resistance to anticancer therapies are the main causes of treatment failure and
      mortality in cancer patients. METHODS: We evaluated invasive markers of urokinase
      plasminogen activator (uPA) and CD44 and multiple drug-resistance (MDR) markers
      of MDR1 and MRP2 in four epithelial ovarian cancer (EOC) cell lines, primary
      tumours (n=120) and matched metastatic lesions (n=40) by immunofluoresence
      labelling. We correlated uPA and CD44 with MDR markers in primary and metastatic
      cells using confocal microscope. We also investigated the relationship of the
      expression of uPA, CD44 and MDR1 with various progression parameters. RESULTS:
      The coexpression of uPA and CD44 with MDR markers was found in primary and
      metastatic cells. The overexpression of uPA, CD44 and MDR1 was found in most
      primary and matched metastatic lesions of EOC, and was significantly associated
      with tumour stage, grade, residual disease status, relapse and presence of
      ascites (P<0.05), but not with histology type (P>0.05). CONCLUSIONS: Our results
      suggest that the overexpression of uPA, CD44 and MRD1 is correlated with EOC
      progression; both uPA and CD44 are related with drug resistance during EOC
      metastasis and could be useful therapeutically.

PMID- 19603019
TI  - Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a
      biomarker of tumour response.
AB  - BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early
      marker of clinical response to treatment in addition to radiological imaging.
      Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes
      cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18
      Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a
      simple, non-invasive way to monitor or predict responses to treatment. METHODS:
      Soluble plasma CK18-Asp396 and CK18 were measured by ELISA from 73 patients with
      advanced gastrointestinal adenocarcinomas before treatment and during
      chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18-Asp396 and
      total CK18 plasma levels were significantly higher in patients compared with the
      healthy volunteers (P=0.015, P<0.001). The total CK18 baseline plasma levels
      before treatment were significantly higher (P=0.009) in patients who develop
      progressive disease than those who achieve partial response or stable disease and
      this correlation was confirmed in an independent validation set. The peak plasma
      levels of CK18 occurring in any cycle following treatment were also found to be
      associated with tumour response, but peak levels of CK18-Asp396 did not reach
      significance (P=0.01, and P=0.07, respectively). CONCLUSION: Plasma levels CK18
      are a potential marker of tumour response in patients with advanced
      gastrointestinal malignancy.

PMID- 19603018
TI  - KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus
      irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer.
AB  - BACKGROUND: KRAS codons 12 and 13 mutations predict resistance to anti-EGFR
      monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E
      mutation has been associated with resistance. Additional KRAS mutations are
      described in CRC. METHODS: We investigated the role of KRAS codons 61 and 146 and
      BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a
      cohort of KRAS codons 12 and 13 wild-type patients. RESULTS: Among 87 KRAS codons
      12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1
      case, respectively. None of mutated patients responded vs 22 of 68 wild type
      (P=0.096). Eleven patients were not evaluable. KRAS mutations were associated
      with shorter progression-free survival (PFS, HR: 0.46, P=0.028). None of 13 BRAF
      mutated patients responded vs 24 of 74 BRAF wild type (P=0.016). BRAF mutation
      was associated with a trend towards shorter PFS (HR: 0.59, P=0.073). In the
      subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a
      lower response rate (0 vs 37%, P=0.047) and worse PFS (HR: 0.45, P=0.023).
      Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%,
      P=0.0005) and PFS (HR: 0.51, P=0.006) compared with KRAS and BRAF wild-type
      patients. CONCLUSION: Assessing KRAS codons 61/146 and BRAF V600E mutations might
      help optimising the selection of the candidate patients to receive anti-EGFR
      moAbs.

PMID- 19603021
TI  - BubR1 as a prognostic marker for recurrence-free survival rates in epithelial
      ovarian cancers.
AB  - BACKGROUND: Epithelial ovarian cancer is one of the most lethal malignancies, and
      has a high recurrence rate. Thus, prognostic markers for recurrence are crucial
      for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome
      instability, we aimed at assessing the prognostic significance of two key mitotic
      kinases, BubR1 and Aurora A. METHODS: We analysed paraffin-embedded tissue
      sections from 160 ovarian cancer patients whose clinical outcomes had been
      tracked after first-line treatment. RESULTS: The median recurrence-free survival
      in patients with a positive and negative expression of BubR1 was 27 and 83
      months, respectively (P<0.001). A positive BubR1 expression was also associated
      with advanced stage, serous histology and high grade. In contrast, Aurora A
      immunostaining did not correlate with any of the clinical parameters analysed.
      CONCLUSION: BubR1, but not Aurora A, is a prognostic marker for recurrence-free
      survival rates in epithelial ovarian cancers.

PMID- 19603020
TI  - Paediatric germ cell tumours and congenital abnormalities: a Children's Oncology
      Group study.
AB  - METHODS: Maternally reported congenital abnormalities (CAs) were examined in a
      case-control study of 278 cases of paediatric germ cell tumours (GCTs) and 423
      controls. RESULTS AND CONCLUSIONS: Germ cell tumours were significantly
      associated with cryptorchidism in males (OR=10.8, 95% CI: 2.1-55.1), but not with
      any other specific CA in either sex.

PMID- 19603022
TI  - High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic
      approach.
AB  - BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel
      disease, known to be associated with a markedly increased risk of colorectal
      carcinoma development. METHODS: Using proteomic analysis with two-dimensional gel
      electrophoresis and mass spectrometry, differentially expressed proteins were
      assessed between UC-associated cancer and sporadic colon cancer cell lines.
      Western blot and immunostaining were performed for confirming the expression.
      RESULTS: Heat-shock protein of 47 kDa (HSP47) was identified as one of the
      proteins expressed more highly in UC-associated cancer cell lines, and an
      immunohistochemical examination confirmed significantly higher levels of HSP47 in
      UC-associated colon cancers than in sporadic counterparts, the expression
      increasing with a progression of neoplastic lesions. Heat-shock protein of 47 kDa
      was further found to be coexpressed with type I collagen in the cytoplasm, and
      both HSP47 and type I collagen were released from cultured cells into the culture
      medium. CONCLUSION: These results suggest that overexpression of HSP47 is a
      unique characteristic of UC-associated carcinoma related to type I collagen
      synthesis, with possible clinical applications.

PMID- 19603023
TI  - Increased expression of ALCAM/CD166 in pancreatic cancer is an independent
      prognostic marker for poor survival and early tumour relapse.
AB  - BACKGROUND: ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is
      a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the
      ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been
      suggested to have a relevant impact on tumour invasion. Although the expression
      of ALCAM is a valuable prognostic and predictive marker in several types of
      epithelial tumours, its role as a prognostic marker in pancreatic cancer has not
      yet been reported. METHODS: In this study, paraffin-embedded samples of 97
      patients with pancreatic cancer undergoing potentially curative resection were
      immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was
      semiquantitatively evaluated and correlated to clinical and histopathological
      parameters. RESULTS: We could show that in normal pancreatic tissue, ALCAM is
      predominantly expressed at the cellular membrane, whereas in pancreatic tumour
      cells, it is mainly localised in the cytoplasm. In addition, univariate and
      multivariate analyses show that increased expression of ALCAM is an adverse
      prognostic factor for recurrence-free and overall survival. Overexpression of
      ADAM17 in pancreatic cancer, however, failed to be a significant prognostic
      marker and was not coexpressed with ALCAM. CONCLUSIONS: Our findings support the
      hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step
      in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant
      independent prognostic marker for poor survival and early tumour relapse in
      pancreatic cancer.

PMID- 19603025
TI  - Societal preference values for advanced melanoma health states in the United
      Kingdom and Australia.
AB  - BACKGROUND: No studies measure preference-based utilities in advanced melanoma
      that capture both intended clinical response and unintended toxicities associated
      with treatment. METHODS: Using standard gamble, utilities were elicited from 140
      respondents in the United Kingdom and Australia for 13 health states. RESULTS:
      Preferences decreased with reduced treatment responsiveness and with increasing
      toxicity. CONCLUSIONS: These general population utilities can be incorporated
      into treatment-specific cost-effectiveness evaluations.

PMID- 19603024
TI  - Prognostic and predictive value of common mutations for treatment response and
      survival in patients with metastatic colorectal cancer.
AB  - BACKGROUND: We address the prognostic and predictive value of KRAS, PIK3CA and
      BRAF mutations for clinical outcomes in response to active agents in the
      treatment of metastatic colorectal cancer (mCRC). METHODS: We determined KRAS,
      BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two
      institutions. All patients received 5-FU-based first-line chemotherapy and
      treatment outcome was analysed retrospectively. RESULTS: KRAS, BRAF and PIK3CA
      mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively.
      Multivariate analysis uncovered BRAF mutation as an independent prognostic factor
      for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1
      7.6). In addition, patients with BRAF-mutant tumours had significantly lower
      progression-free survival (PFS: HR 4.0, 95% CI 2.2-7.4) than those whose tumors
      that carried wild-type BRAF. Among 92 patients treated using chemotherapy and
      cetuximab as salvage therapy, KRAS mutation was associated with lack of response
      (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations
      also predicted reduced PFS in response to cetuximab salvage therapy. CONCLUSIONS:
      These results underscore the potential of mutational profiling to identify CRCs
      with different natural histories or treatment responses. The adverse significance
      of BRAF mutation should inform patient selection and stratification in clinical
      trials.

PMID- 19603026
TI  - EBV-associated gastric carcinoma in high- and low-incidence areas for
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Approximately 10% of gastric carcinomas are associated with Epstein
      Barr virus (EBV). The Inuit in Greenland have a high incidence of EBV-associated
      nasopharyngeal carcinoma. METHODS: We conducted a population-based case-control
      study comparing gastric carcinomas in Greenland and in Denmark. RESULTS: The
      prevalence rate of EBV-associated gastric carcinomas was 8.5% in both
      populations. CONCLUSION: The findings of this study argue against a general
      susceptibility to EBV-associated carcinomas among the Inuit.

PMID- 19603028
TI  - Can cutaneous telangiectasiae as late normal-tissue injury predict cardiovascular
      disease in women receiving radiotherapy for breast cancer?
AB  - BACKGROUND: Overall, approximately 5% of patients show late normal-tissue damage
      after radiotherapy with a smaller number having a risk of radiation-induced heart
      disease. Although the data are conflicting, large studies have shown increased
      risks of cardiovascular disease (CVD) for irradiated patients compared with non
      irradiated ones, or for those treated to the left breast or chest wall compared
      with those treated to the right. Cutaneous telangiectasiae as late normal-tissue
      injury have so far only been regarded as a cosmetic burden. METHODS: The
      relationship between late normal-tissue radiation injury phenotypes in 149
      irradiated breast cancer patients and the presence of cardiovascular disease were
      examined. RESULTS: A statistically significant association between the presence
      of skin telangiectasiae and the long-term risk of CVD was shown in these patients
      (P=0.017; Fisher's exact test). INTERPRETATION: This association may represent
      initial evidence that telangiectasiae can be used as a marker of future radiation
      induced cardiac complications. It could also suggest a common biological pathway
      for the development of both telangiectasiae and CVD on the basis of a genetically
      predisposed endothelium. To our knowledge this is the first reported study
      looking at this association.

PMID- 19603027
TI  - Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark
      of cerebellar and optic pathway tumours.
AB  - BACKGROUND: Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade
      astrocytomas (LGA), are common, heterogeneous and poorly understood subset of
      brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes
      formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF
      was recently identified in a proportion of LGA, and may be involved in their
      pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA
      and whether incidence of 7q34 duplication is associated with tumour type or
      location. METHODS AND RESULTS: Using Illumina-Human-Hap300-Duo and 610-Quad high
      resolution-SNP-based arrays and quantitative PCR on genes of interest, we
      investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific
      to sporadic JPA (35 of 53 - 66%) and does not occur in other LGA subtypes (0 of
      27) or NF1-associated-JPA (0 of 4). We also establish that it is site specific as
      it occurs in the majority of cerebellar JPA (24 of 30 - 80%) followed by
      brainstem, hypothalamic/optic pathway JPA (10 of 16 - 62.5%) and is rare in
      hemispheric JPA (1 of 7 - 14%). The MAP-kinase pathway, assessed through ERK
      phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain
      of function studies performed on hTERT-immortalised astrocytes show that
      overexpression of wild-type BRAF does not increase cell proliferation or baseline
      MAPK signalling even if it sensitises cells to EGFR stimulation. CONCLUSIONS AND
      INTERPRETATION: Our results suggest that variants of JPA might arise from a
      unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this
      tumour-type in association to MAPK-kinase pathway activation, potentially plays a
      site-specific role in their pathogenesis. Importantly, gain of function
      abnormalities in components of MAP-Kinase signalling are potentially present in
      all JPA making this tumour amenable to therapeutic targeting of this pathway.

PMID- 19603029
TI  - A study of pyrimidine base damage in relation to oxidative stress and cancer.
AB  - BACKGROUND: A long-standing hypothesis is that oxidative stress is a risk factor
      for cancer. Support for this hypothesis comes from observations of higher levels
      of oxidative damage in the DNA of WBC of cancer patients compared with healthy
      controls. METHODS: Two generally overlooked types of DNA damage, the formamide
      modification and the thymine glycol modification, both derived from pyrimidine
      bases, were assayed as markers of oxidative stress. Damage levels were measured
      in the DNA of WBC of ovarian cancer patients and of healthy controls. RESULTS:
      The levels of both modifications were higher in ovarian cancer patients than in
      healthy controls although in the case of the formamide modification age could not
      be ruled out as a factor. CONCLUSION: Our results in combination with other
      published measurements of oxidative DNA damage support the hypothesis that
      oxidative damage, on average, is higher in WBC of cancer patients than in healthy
      controls.

PMID- 19603030
TI  - The opposing roles of Wnt-5a in cancer.
AB  - Wnt-5a is one of the most highly investigated non-canonical Wnts and has been
      implicated in almost all aspects of non-canonical Wnt signalling. In terms of
      cancer development, Wnt-5a has, until recently, lived in the shadow of its better
      characterised relatives. This was largely because of its apparent inability to
      transform cells or signal through the canonical beta-catenin pathway that is so
      important in cancer, particularly colorectal cancer. Recent work in a wide range
      of human tumours has pointed to a critical role for Wnt-5a in malignant
      progression, but there is conflicting evidence whether Wnt-5a has a tumour
      promoting or -suppressing role. Emerging evidence suggests that the functions of
      Wnt-5a can be drastically altered depending on the availability of key receptors.
      Hence, the presence or absence of these receptors may go some way to explain the
      conflicting role of Wnt-5a in different cancers. This review summarises our
      current understanding of Wnt-5a and cancer.

PMID- 19603032
TI  - Dasatinib inhibits the growth of prostate cancer in bone and provides additional
      protection from osteolysis.
AB  - BACKGROUND: Dasatinib is a small molecule kinase inhibitor that has recently been
      shown to inhibit Src family kinases (SFK) and also has activity against CaP. Of
      importance to metastatic CaP, which frequently metastasises to bone, SFK are also
      vital to the regulation of bone remodelling. We sought to determine the ability
      of dasatinib to inhibit growth of CaP in bone. METHODS: C4-2B CaP cells were
      injected into tibiae of SCID mice and treated with dasatinib, alone or in
      combination with docetaxel. Serum prostate-specific antigen levels, bone mineral
      density, radiographs and histology were analysed. RESULTS: Treatment with
      dasatinib alone significantly lowered sacrifice serum prostate-specific antigen
      levels compared to control, 2.3+/-0.4 vs 9.2+/-2.1 (P=0.004). Combination therapy
      improved efficacy over dasatinib alone (P=0.010). Dasatinib increased bone
      mineral density in tumoured tibiae by 25% over control tumoured tibiae (P<0.001).
      CONCLUSION: Dasatinib inhibits growth of C4-2B cells in bone with improved
      efficacy when combined with docetaxel. Additionally, dasatinib inhibits
      osteolysis associated with CaP. These data support further study of dasatinib in
      clinical trials for men with CaP bone metastases.

PMID- 19603031
TI  - Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: To assess the efficacy and safety of S-1 and cisplatin with
      concurrent thoracic radiation for unresectable stage III non-small-cell lung
      cancer (NSCLC). METHODS: Eligible patients were 20-74 years old and had
      histologically or cytologically confirmed NSCLC, a performance status of 0-1, and
      no prior chemotherapy. Patients were treated with cisplatin (60 mg m(-2) on day
      1) and S-1 (orally at 40 mg m(-2) per dose, b.i.d., on days 1-14), with the
      treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy
      thoracic radiation dose was delivered in 30 fractions. RESULTS: Of 50 patients,
      48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI:
      79.1-96.9%). This regimen was well tolerated. Common toxicities included grade
      3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia
      (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3
      pneumonitis (5%). Median progression-free survival was 12.0 months and median
      overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and
      56%, respectively. CONCLUSION: This chemotherapy regimen with concomitant
      radiotherapy is a promising treatment for locally advanced NSCLC because of its
      high response rates, good survival rates, and mild toxicities.

PMID- 19603033
TI  - MLH1 expression sensitises ovarian cancer cells to cell death mediated by XIAP
      inhibition.
AB  - BACKGROUND: The X-linked inhibitor of apoptosis protein (XIAP), an endogenous
      apoptosis suppressor, can determine the level of caspase accumulation and the
      resultant response to apoptosis-inducing agents such as cisplatin in epithelial
      ovarian cancer (EOC). In addition, the mismatch repair protein, hMLH1, has been
      linked to DNA damage-induced apoptosis by cisplatin by both p53-dependent and 
      independent mechanisms. METHODS: In this study, hMLH1 expression was correlated
      with clinical response to platinum drugs and survival in advanced stage (III-IV)
      EOC patients. We then investigated whether MLH1 loss was a determinant in anti
      apoptosis response to cisplatin mediated by XIAP in isogenic and established EOC
      cell lines with differential p53 status. RESULTS: The percentage of cells
      undergoing cisplatin-induced cell killing was higher in MLH1-proficient cells
      than in MLH1-defective cells. In addition, the presence of wild-type hMLH1 or
      hMLH1 re-expression significantly increased sensitivity to 6-thioguanine, a MMR
      dependent agent. Cell-death response to 6-thioguanine and cisplatin was
      associated with significant proteolysis of MLH1, with XIAP destabilisation and
      increased caspase-3 activity. The siRNA-mediated inhibition of XIAP increased
      MLH1 proteolysis and cell death in MLH1-proficient cells but not in MLH1
      defective cells. CONCLUSION: These data suggest that XIAP inhibitors may prove to
      be an effective means of sensitising EOC to MLH1-dependent apoptosis.

PMID- 19603036
TI  - Introduction to the genomics spotlight.

PMID- 19603035
TI  - Genomic technologies in leukemia and lymphoma: a review series.

PMID- 19603038
TI  - Random versus directionally persistent cell migration.
AB  - Directional migration is an important component of cell motility. Although the
      basic mechanisms of random cell movement are well characterized, no single model
      explains the complex regulation of directional migration. Multiple factors
      operate at each step of cell migration to stabilize lamellipodia and maintain
      directional migration. Factors such as the topography of the extracellular
      matrix, the cellular polarity machinery, receptor signalling, integrin
      trafficking, integrin co-receptors and actomyosin contraction converge on
      regulation of the Rho family of GTPases and the control of lamellipodial
      protrusions to promote directional migration.

PMID- 19603041
TI  - Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme
      activity is responsible for erectile dysfunction in a rat model of
      atherosclerosis.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide
      synthase (NOS), is mainly metabolized by N(G),N(G)-dimethylarginine
      dimethylaminohydrolase (DDAH). We investigated whether altered cavernosal ADMA
      DDAH metabolism might cause impairment of erection in rat model of
      atherosclerosis (AS). Male Sprague-Dawley rats (3 months old) were divided into
      an AS group and a normal control (Con) group (n=20 in each group). The AS rats
      received AS-prone treatment (6 weeks of 1% cholesterol diet plus early 2 weeks of
      N(G)-nitro-L-arginine methyl ester (3 mg ml(-1) per day) treatment). After 6
      weeks, rats underwent cavernosometry measuring the maximal intracavernosal
      pressure/mean arterial pressure (ICP/MAP) ratios as a surrogate marker of
      erectile function. The amount of cavernosal ADMA was assessed by immunoblot
      analysis and correlated with the ICP/MAP. Isoform-specific DDAH expression was
      compared by immunohistochemistry. Cavernosal DDAH and NOS activity were measured.
      Cavernosal malondialdehyde levels were assayed to determine the degree of lipid
      peroxidation. Compared to the controls, the AS rats had signs of impaired
      erectile function. Higher cavernosal ADMA was observed in the AS rats. The
      cavernosal ADMA had a moderately negative correlation with the ICP/MAP.
      Immunohistochemistry revealed the expression of both isoforms was not affected by
      the presence of AS. However, significantly diminished DDAH as well as NOS
      activity was observed in the AS group. In addition, elevated cavernosal
      malondialdehyde levels were noted in the AS rats. Our study showed that decreased
      cavernosal DDAH activity is the cause of cavernosal ADMA accumulation leading to
      reduced cavernosal NOS activity and impairment of erectile function.

PMID- 19603040
TI  - Epigenetic dynamics of stem cells and cell lineage commitment: digging
      Waddington's canal.
AB  - Cells of the early mammalian embryo, including pluripotent embryonic stem (ES)
      cells and primordial germ cells (PGCs), are epigenetically dynamic and
      heterogeneous. During early development, this heterogeneity of epigenetic states
      is associated with stochastic expression of lineage-determining transcription
      factors that establish an intimate crosstalk with epigenetic modifiers. Lineage
      specific epigenetic modification of crucial transcription factor loci (for
      example, methylation of the Elf5 promoter) leads to the restriction of
      transcriptional circuits and the fixation of lineage fate. The intersection of
      major epigenetic reprogramming and programming events in the early embryo creates
      plasticity followed by commitment to the principal cell lineages of the early
      conceptus.

PMID- 19603043
TI  - Can open-label studies demonstrate efficacy in improving sexual function?

PMID- 19603044
TI  - The australasian society for dermatology research: a new player on the team.

PMID- 19603039
TI  - Rab GTPases as coordinators of vesicle traffic.
AB  - Membrane trafficking between organelles by vesiculotubular carriers is
      fundamental to the existence of eukaryotic cells. Central in ensuring that
      cargoes are delivered to their correct destinations are the Rab GTPases, a large
      family of small GTPases that control membrane identity and vesicle budding,
      uncoating, motility and fusion through the recruitment of effector proteins, such
      as sorting adaptors, tethering factors, kinases, phosphatases and motors.
      Crosstalk between multiple Rab GTPases through shared effectors, or through
      effectors that recruit selective Rab activators, ensures the spatiotemporal
      regulation of vesicle traffic. Functional impairments of Rab pathways are
      associated with diseases, such as immunodeficiencies, cancer and neurological
      disorders.

PMID- 19603048
TI  - Defining Ro positivity.

PMID- 19603049
TI  - Immunology and skin disease 2009: frontiers in cutaneous immunology.

PMID- 19603050
TI  - Langerhans cell migration: not necessarily always at the center of the skin
      sensitization universe.
AB  - Since their discovery in 1868, the role of Langerhans cells (LCs) in skin
      immunity has been researched extensively. Recent data deriving from transgenic
      animals that are deficient in LCs have begun to challenge the dogma that there is
      a universal requirement for these cells in the development of skin sensitization.
      This Commentary addresses relationships between LC mobilization, draining lymph
      node activation, and skin sensitization using immunomodulators agonistic for a
      family of sphingosine-1-phosphate (S1P) receptors.

PMID- 19603051
TI  - Protein kinase Cepsilon reveals importance of extrinsic apoptosis in preventing
      UV carcinogenesis.
AB  - UV-induced apoptosis, giving rise to "sunburn cells," has been thought to be
      primarily cell autonomous (or intrinsic) in nature, triggered by DNA damage and
      mediated through p53. However, in vivo the microenvironment appears to contribute
      to UV-induced apoptosis by activating the extrinsic route through death
      receptors. Protein kinase Cvarepsilon lowers UV-induced expression of Fas and its
      downstream proteins in this extrinsic route, suppressing apoptosis and enhancing
      UV carcinogenesis.

PMID- 19603052
TI  - Flii control: balancing migration and adhesion.
AB  - Wound healing in the skin requires a compromise between adhesion and migration.
      Both processes include modulation of the cytoskeleton, cell-surface receptors,
      and receptor ligands., In this issue, Kopecki et al. demonstrate that
      overexpression of Flii, an actin-remodeling protein, impedes wound healing but
      inhibits hemidesmosome formation. In contrast, Flii deficiency results in
      enhanced wound healing while promoting hemidesmosome assembly. We discuss
      potential mechanisms that could explain how this unique gelsolin family member
      might regulate both stable keratinocyte adhesion and motility.

PMID- 19603053
TI  - Hyaluronan accumulation in wounded epidermis: a mediator of keratinocyte
      activation.
AB  - The high-molecular-mass polysaccharide hyaluronan is abundant in the
      extracellular space between adjacent keratinocytes throughout the vital part of
      epidermis. It has a rapid turnover, and its content is subject to large
      fluctuations due to physiological and environmental conditions, with the
      strongest effects mediated by EGFR signaling. Using an elegant organotypic
      culture system, Monslow et al. (2009, this issue) demonstrate that heparin
      binding (HB)-EGF released from its membrane anchor is the major ligand of EGFR in
      injured epidermis, accounting for the autocrine and paracrine activation of
      hyaluronan synthesis by the keratinocytes in the neighborhood, thus facilitating
      the epidermal wound-healing response.

PMID- 19603054
TI  - High-dose short-term folate administration modifies ambulatory blood pressure in
      postmenopausal women. A placebo-controlled study.
AB  - In humans low intake or low levels of folate are related to elevated homocysteine
      (Hcy) or blood pressure (BP). This study was performed to test whether in healthy
      postmenopausal women a 3-week administration of folate (5-methyltetrahydrofolate:
      5-MTHF) at the dose of 15 mg/day (n=15), was, in comparison to placebo (n=15),
      capable of modifying 24-h ambulatory BP, along with Hcy and insulin metabolism.
      Placebo did not modify any parameter. 5-MTHF significantly decreased nocturnal
      systolic (-4.48+/-1.8 mm Hg; P=0.029), diastolic (-5.33+/-1.3 mm Hg; P=0.001) and
      mean (-5.10+/-1.1 mm Hg; P=0.005) BP, in a way that was significantly different
      from that observed during placebo. 5-MTHF also reduced Hcy (11.77+/-1.15 vs
      8.71+/-0.50 micromol/l; P=0.03), and insulin resistance, evaluated by HOMA-IR
      (2.58+/-0.04 vs 2.03+/-0.04; P=0.01). Whether maintained in the long term, 5
      MTHF's cardiovascular and metabolic effect may contribute to primary
      cardiovascular prevention of postmenopausal women.

PMID- 19603055
TI  - Characteristics of women who frequently under report their energy intake: a
      doubly labelled water study.
AB  - BACKGROUND/OBJECTIVES: We applied three dietary assessment methods and aimed at
      obtaining a set of physical, social and psychological variables that can
      discriminate those individuals who did not underreport ('never under-reporters'),
      those who underreported in one dietary assessment method ('occasional under
      reporters') and those who underreported in two or three dietary assessment
      methods ('frequent under-reporters'). PARTICIPANTS/METHODS: Sixty-five women aged
      18-57 years were recruited for this study. Total energy expenditure was
      determined by doubly labelled water, and energy intake was estimated by three 24
      h diet recalls, 3-day food records and a food frequency questionnaire. A multiple
      discriminant analysis was used to identify which of those variables better
      discriminated the three groups: body mass index (BMI), income, education, social
      desirability, nutritional knowledge, dietary restraint, physical activity
      practice, body dissatisfaction and binge-eating symptoms. RESULTS: Twenty-three
      participants were 'never under-reporters'. Twenty-four participants were
      'occasional under-reporters' and 18 were 'frequent under-reporters'. Four
      variables entered the discriminant model: income, BMI, social desirability and
      body dissatisfaction. According to potency indices, income contributed the most
      to the total discriminant power, followed in decreasing order by social
      desirability score, BMI and body dissatisfaction. Income, social desirability and
      BMI were the characteristics that mainly separated the 'never under-reporters'
      from the under-reporters (occasional or frequent). Body dissatisfaction better
      discriminated the 'occasional under-reporters' from the 'frequent under
      reporters'. CONCLUSIONS: 'Frequent under-reporters' have a greater BMI, social
      desirability score, body dissatisfaction score and lower income. These four
      variables seemed to be able to discriminate individuals who are more prone to
      systematic under reporting.

PMID- 19603056
TI  - New insights into symptoms and neurocircuit function of anorexia nervosa.
AB  - Individuals with anorexia nervosa have a relentless preoccupation with dieting
      and weight loss that results in severe emaciation and sometimes death. It is
      controversial whether such symptoms are secondary to psychosocial influences, are
      a consequence of obsessions and anxiety or reflect a primary disturbance of brain
      appetitive circuits. New brain imaging technology provides insights into ventral
      and dorsal neural circuit dysfunction - perhaps related to altered serotonin and
      dopamine metabolism - that contributes to the puzzling symptoms found in people
      with eating disorders. For example, altered insula activity could explain
      interoceptive dysfunction, and altered striatal activity might shed light on
      altered reward modulation in people with anorexia nervosa.

PMID- 19603057
TI  - Bayesian shrinkage mapping for multiple QTL in half-sib families.
AB  - Recently, an effective Bayesian shrinkage estimation method has been proposed for
      mapping QTL in inbred line crosses. However, with regard to outbred populations,
      such as half-sib populations with maternal information unavailable, it is not
      straightforward to utilize such a shrinkage estimation for QTL mapping. The
      reasons are: (1) the linkage phase of markers in the outbred population is
      usually unknown; and (2) only paternal genotypes can be used for inferring QTL
      genotypes of offspring. In this article, a novel Bayesian shrinkage method was
      proposed for mapping QTL under the half-sib design using a mixed model. A
      simulation study clearly demonstrated that the proposed method was powerful for
      detecting multiple QTL. In addition, we applied the proposed method to map QTL
      for economic traits in the Chinese dairy cattle population. Two or more novel QTL
      harbored in the chromosomal region were detected for each trait of interest,
      whereas only one QTL was found using traditional maximum likelihood analyses in
      our earlier studies. This further validated that our shrinkage estimation method
      could perform well in empirical data analyses and had practical significance in
      the field of linkage studies for outbred populations.

PMID- 19603058
TI  - Estimating gametic introgression rates in a risk assessment context: a case study
      with Scots pine relicts.
AB  - The estimation of recent gene immigration is fundamental to a wide range of
      evolutionary and conservation studies. In a risk assessment context, gene flow
      estimation procedures are needed that are both accurate and readily amenable to
      formal evaluation of statistical uncertainty. However, genetic methods for
      estimating recent migration rates that are specific and have been thoroughly
      evaluated are scarce. Here we use an original and straightforward maximum
      likelihood method to estimate recent uniparental gametic immigration from non
      local plantations into an endangered population of the Iberian relict pine
      variety Pinus sylvestris var. nevadensis D. H. Christ. Our approach is not
      intended to ascertain population membership of individuals, but rather to obtain
      accurate immigration rate estimates with reliable confidence limits. We found
      very high (approximately 40%) pollen introgression at the seed-crop level into
      the Scots pine relict, and substantial (10-15%) male gametic introgression among
      naturally regenerated recruits. Using numerical simulation, we show that our
      method yields uniparental gametic immigration estimates that are expected to be
      virtually unbiased and usually accurate under our sampling conditions. Among four
      tested methods to estimate the confidence intervals for immigration estimates,
      the profile-likelihood method was the best, as it outperformed bootstrapping
      procedures and yielded coverage close to nominal limits under different sample
      sizes and migration rates. This study presents a method by which researchers can
      facilitate decision making within a gene flow risk assessment context.

PMID- 19603059
TI  - Roaches, apoptosis and the ovarian clock: use it or lose it.

PMID- 19603060
TI  - Dosage and parent-of-origin effects shaping aneuploid swarms in A. thaliana.
AB  - Changes in chromosome number have a critical role in the evolution and formation
      of plant species. Triploids, which carry three complete sets of chromosomes, in
      particular produce offspring with different chromosome numbers, including diploid
      and tetraploid progeny, as well as a swarm of aneuploid progeny, which carry
      incomplete chromosome sets. In this study, we investigated the mechanisms shaping
      these swarms at the population level through a detailed characterization of the
      progeny of triploid Arabidopsis thaliana. We report that triploid meiosis
      predominately produced aneuploid gametes, most of which were viable. We performed
      reciprocal crosses between triploid and either diploid or tetraploid plants and
      karyotyped all surviving individuals. This allowed us to dissect the parent-of
      origin (cross-direction) effects and also the effect of the dosage of the
      crossing partner on the inheritance of each chromosome type. Overall, our data
      indicate that the chromosomal composition of the swarms produced by the triploid
      A. thaliana were strongly influenced by selection acting against specific gamete
      combinations, but not necessarily associated with aneuploidy. Finally, each of
      the five chromosome types responded differently to this selection, suggesting the
      presence of dosage-sensitive factor(s) critical for viability and encoded on
      different chromosomes.

PMID- 19603061
TI  - Wolf of a different colour.

PMID- 19603062
TI  - Long-term changes in the fine-scale population structure of coho salmon
      populations (Oncorhynchus kisutch) subject to extensive supportive breeding.
AB  - The long-term viability of a metapopulation depends partly on the gene flow among
      sub-populations. Management approaches such as translocations and supportive
      breeding between closely related populations may affect gene flow and overall
      structure, and therefore viability. Here, we examined temporal changes in the
      fine-scale population structure of coho salmon (Oncorhynchus kisutch) by
      comparing archived (1938) and modern (2001-2005) populations in six rivers within
      a single conservation unit (Puget Sound, Washington) sampled before and after an
      extended period of between-river transfers and releases of millions of cultured
      salmon. Genotype frequencies at eight microsatellite loci showed that current
      populations descended from historical Puget Sound populations, but populations in
      different rivers that exchanged fish for hatchery propagation share more of their
      ancestry recently than they did historically. Historically, populations in
      different rivers were isolated by geographic distance, but that relationship is
      no longer significant. Allelic richness among all populations declined
      significantly, suggesting that genetic drift has increased because of a
      population bottleneck. Populations in different rivers and within the same river
      have become more diverged, providing further evidence for a widespread
      bottleneck. Previously, we observed that genetic distance significantly decreased
      with the number of fish exchanged; however, some populations apparently resisted
      introgression. Altered gene flow and lost diversity may affect the complexity,
      and therefore resiliency of sub-populations within a conservation unit. Plans for
      artificial culture need to maintain existing genetic diversity and avoid
      disrupting the fine-scale structure by using local populations for parents
      whenever possible.

PMID- 19603063
TI  - Maternal and paternal genealogy of Eurasian taurine cattle (Bos taurus).
AB  - Maternally inherited mitochondrial DNA (mtDNA) has been used extensively to
      determine origin and diversity of taurine cattle (Bos taurus) but global surveys
      of paternally inherited Y-chromosome diversity are lacking. Here, we provide
      mtDNA information on previously uncharacterised Eurasian breeds and present the
      most comprehensive Y-chromosomal microsatellite data on domestic cattle to date.
      The mitochondrial haplogroup T3 was the most frequent, whereas T4 was detected
      only in the Yakutian cattle from Siberia. The mtDNA data indicates that the
      Ukrainian and Central Asian regions are zones where hybrids between taurine and
      zebu (B. indicus) cattle have existed. This zebu influence appears to have
      subsequently spread into southern and southeastern European breeds. The most
      common Y-chromosomal microsatellite haplotype, termed here as H11, showed an
      elevated frequency in the Eurasian sample set compared with that detected in Near
      Eastern and Anatolian breeds. The taurine Y-chromosomal microsatellite haplotypes
      were found to be structured in a network according to the Y-haplogroups Y1 and
      Y2. These data do not support the recent hypothesis on the origin of Y1 from the
      local European hybridization of cattle with male aurochsen. Compared with mtDNA,
      the intensive culling of breeding males and male-mediated crossbreeding of
      locally raised native breeds has accelerated loss of Y-chromosomal variation in
      domestic cattle, and affected the contribution of genetic drift to diversity. In
      conclusion, to maintain diversity, breeds showing rare Y-haplotypes should be
      prioritised in the conservation of cattle genetic resources.

PMID- 19603064
TI  - SMN transcript levels in leukocytes of SMA patients determined by absolute real
      time PCR.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      caused by homozygous mutations of the SMN1 gene. Three forms of SMA are
      recognized (type I-III) on the basis of clinical severity. All patients have at
      least one or more (usually 2-4) copies of a highly homologous gene (SMN2), which
      produces insufficient levels of functional SMN protein, because of alternative
      splicing of exon 7. Recently, evidence has been provided that SMN2 expression can
      be enhanced by pharmacological treatment. However, no reliable biomarkers are
      available to test the molecular efficacy of the treatments. At present, the only
      potential biomarker is the dosage of SMN products in peripheral blood. However,
      the demonstration that SMN full-length (SMN-fl) transcript levels are reduced in
      leukocytes of patients compared with controls remains elusive (except for type
      I). We have developed a novel assay based on absolute real-time PCR, which allows
      the quantification of SMN1-fl/SMN2-fl transcripts. For the first time, we have
      shown that SMN-fl levels are reduced in leukocytes of type II-III patients
      compared with controls. We also found that transcript levels are related to
      clinical severity as in type III patients SMN2-fl levels are significantly higher
      compared with type II and directly correlated with functional ability in type II
      patients and with age of onset in type III patients. Moreover, in haploidentical
      siblings with discordant phenotype, the less severely affected individuals showed
      significantly higher transcript levels. Our study shows that SMN2-fl dosage in
      leukocytes can be considered a reliable biomarker and can provide the rationale
      for SMN dosage in clinical trials.

PMID- 19603065
TI  - DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3.
AB  - Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual
      severe to profound sensorineural hearing loss, provided evidence for a DFNB locus
      on human chromosome 9q34.3. Co-segregation of the deafness trait with marker
      D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at
      theta=0). Two additional large families, PKDF517 and PKDF741, co-segregate
      recessive deafness with markers linked to the same interval. Haplotype analyses
      of these three families refined the interval to 3.84 Mb defined by D9S1818
      (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously
      reported DFNB33 locus whose chromosomal map position has been recently revised
      and assigned to a new position on chromosome 10p11.23-q21.1. The nonsyndromic
      deafness locus on chromosome 9q segregating in family PKDF280 was designated
      DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations
      and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602.

PMID- 19603066
TI  - Support for the involvement of complement factor I in age-related macular
      degeneration.

PMID- 19603067
TI  - In vitro readthrough of termination codons by gentamycin in the Stuve-Wiedemann
      Syndrome.
AB  - The Stuve-Wiedemann Syndrome (SWS) is a frequently lethal chondrodysplasia caused
      by null mutations in the leukemia inhibitory factor receptor gene (LIFR)
      responsible for an impaired activation of the JAK-STAT pathway after LIF
      stimulation. Most LIFR mutations are nonsense mutations, thus prompting us to
      investigate the impact of aminoglycosides on the readthrough of premature
      termination codons (PTCs). Culturing skin fibroblasts from three SWS patients and
      controls for 48 h in the presence of gentamycin (200-500 microg/ml) partially
      restored the JAK-STAT3 pathway when stimulated by LIF. Consistently, quantitative
      RT-PCR analysis showed that gentamycin stabilized LIFR mRNAs carrying UGA
      premature termination codons. We conclude that high gentamycin concentrations can
      partially restore functional LIFR protein synthesis in vitro, prompting us to
      investigate PTC readthrough using less toxic and more efficient drugs in this
      presently untreatable lethal condition.

PMID- 19603068
TI  - ProteinArchitect: protein evolution above the sequence level.
AB  - BACKGROUND: While many authors have discussed models and tools for studying
      protein evolution at the sequence level, molecular function is usually mediated
      by complex, higher order features such as independently folding domains and
      linear motifs that are based on or embedded in a particular arrangment of
      features such as secondary structure elements, transmembrane domains and regions
      with intrinsic disorder. This 'protein architecture' can, in its most simplistic
      representation, be visualized as domain organization cartoons that can be used to
      compare proteins in terms of the order of their mostly globular domains.
      METHODOLOGY: Here, we describe a visual approach and a webserver for protein
      comparison that extend the domain organization cartoon concept. By developing an
      information-rich, compact visualization of different protein features above the
      sequence level, potentially related proteins can be compared at the level of
      propensities for secondary structure, transmembrane domains and intrinsic
      disorder, in addition to PFAM domains. A public Web server is available at
      www.proteinarchitect.net, while the code is provided at
      protarchitect.sourceforge.net. CONCLUSIONS/SIGNIFICANCE: Due to recent advances
      in sequencing technologies we are now flooded with millions of predicted proteins
      that await comparative analysis. In many cases, mature tools focused on revealing
      hits with considerable global or local similarity to well-characterized proteins
      will not be able to lead us to testable hypotheses about a protein's function, or
      the function of a particular region. The visual comparison of different types of
      protein features with ProteinArchitect will be useful when assessing the
      relevance of similarity search hits, to discover subgroups in protein families
      and superfamilies, and to understand protein regions with conserved features
      outside globular regions. Therefore, this approach is likely to help researchers
      to develop testable hypotheses about a protein's function even if is somewhat
      distant from the more characterized proteins, by facilitating the discovery of
      features that are conserved above the sequence level for comparison and further
      experimental investigation.

PMID- 19603069
TI  - Contrasting role of octopamine in appetitive and aversive learning in the crab
      Chasmagnathus.
AB  - BACKGROUND: Biogenic amines are implicated in reinforcing associative learning.
      Octopamine (OA) is considered the invertebrate counterpart of noradrenaline and
      several studies in insects converge on the idea that OA mediates the reward in
      appetitive conditioning. However, it is possible to assume that OA could have a
      different role in an aversive conditioning. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we pharmacologically studied the participation of OA in two learning processes in
      the crab Chasmagnathus granulatus, one appetitive and one aversive. It is shown
      that the aversive memory is impaired by an OA injection applied immediately or 30
      minutes after the last training trial. By contrast, the appetitive memory is
      blocked by OA antagonists epinastine and mianserine, but enhanced by OA when
      injected together with the supply of a minimum amount of reinforcement. Finally,
      double-learning experiments in which crabs are given the aversive and the
      appetitive learning either successively or simultaneously allow us to study the
      interaction between both types of learning and analyze the presumed action of OA.
      We found that the appetitive training offered immediately, but not one hour,
      after an aversive training has an amnesic effect on the aversive memory,
      mimicking the effect and the kinetic of an OA injection.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the role of OA is
      divergent in two memory processes of opposite signs: on the one hand it would
      mediate the reinforcement in appetitive learning, and on the other hand it has a
      deleterious effect over aversive memory consolidation.

PMID- 19603070
TI  - Malignant catarrhal fever of cattle is associated with low abundance of IL-2
      transcript and a predominantly latent profile of ovine herpesvirus 2 gene
      expression.
AB  - BACKGROUND: Malignant catarrhal fever (MCF) is a lethal disease of cattle,
      characterized by vasculitis, necrosis, and accumulation of activated,
      dysregulated cytotoxic lymphocytes in various tissues. Ovine gamma herpesvirus 2
      (OvHV-2) is a causative agent of MCF, which may trigger the disease through
      immunopathogenic pathways. Lymphocytes are the main target of the virus. However,
      the pathogenic basis of the disease is still mysterious. METHODS/FINDINGS: We
      hypothesized that the gene expression patterns of OvHV-2 and the relative
      abundances of host cell transcripts in lymphnodes may be used to identify
      pathways that help to explain the pathogenesis of MCF. Therefore, viral and host
      cell gene expression patterns in lymph nodes of animals with MCF and healthy
      controls were analyzed by microarray. Two regions on the viral genome were
      transcriptionally active, one encoding an orthologue to the latency-associated
      nuclear antigen (ORF73) of other gamma herpesviruses, the other with no predicted
      open reading frame. A vast number of transcripts related to inflammatory
      processes, lymphocyte activation, cell proliferation and apoptosis were detected
      at different abundances. However, the IL-2 transcript was eminent among the
      transcripts, which were, compared to healthy controls, less abundant in animals
      with MCF. The ratio between CD4- and CD8-positive T-lymphocytes was decreased in
      the lymphnodes of animals with MCF compared to healthy controls. In contrast, the
      same ratio was stable, when peripheral blood lymphocytes were analyzed.
      CONCLUSIONS/SIGNIFICANCE: The phenotype of mice with a deficient IL-2-system
      almost perfectly matches the clinical signs observed in cattle with MCF, which
      feature a significantly decreased IL-2 transcript abundance, compared to healthy
      cattle. This supports the hypothesis that immunopathogenic events are linked to
      the pathogenesis of MCF. IL-2-deficiency may play an important role in the
      process. Therefore, this work opens new avenues for research on MCF.

PMID- 19603071
TI  - Top-down lipidomics reveals ether lipid deficiency in blood plasma of
      hypertensive patients.
AB  - BACKGROUND: Dyslipoproteinemia, obesity and insulin resistance are integrative
      constituents of the metabolic syndrome and are major risk factors for
      hypertension. The objective of this study was to determine whether hypertension
      specifically affects the plasma lipidome independently and differently from the
      effects induced by obesity and insulin resistance. METHODOLOGY/PRINCIPAL
      FINDINGS: We screened the plasma lipidome of 19 men with hypertension and 51
      normotensive male controls by top-down shotgun profiling on a LTQ Orbitrap hybrid
      mass spectrometer. The analysis encompassed 95 lipid species of 10 major lipid
      classes. Obesity resulted in generally higher lipid load in blood plasma, while
      the content of tri- and diacylglycerols increased dramatically. Insulin
      resistance, defined by HOMA-IR >3.5 and controlled for BMI, had little effect on
      the plasma lipidome. Importantly, we observed that in blood plasma of
      hypertensive individuals the overall content of ether lipids decreased. Ether
      phosphatidylcholines and ether phosphatidylethanolamines, that comprise
      arachidonic (20:4) and docosapentaenoic (22:5) fatty acid moieties, were
      specifically diminished. The content of free cholesterol also decreased, although
      conventional clinical lipid homeostasis indices remained unaffected.
      CONCLUSIONS/SIGNIFICANCE: Top-down shotgun lipidomics demonstrated that
      hypertension is accompanied by specific reduction of the content of ether lipids
      and free cholesterol that occurred independently of lipidomic alterations induced
      by obesity and insulin resistance. These results may form the basis for novel
      preventive and dietary strategies alleviating the severity of hypertension.

PMID- 19603072
TI  - Eyes wide shut: amygdala mediates eyes-closed effect on emotional experience with
      music.
AB  - The perceived emotional value of stimuli and, as a consequence the subjective
      emotional experience with them, can be affected by context-dependent styles of
      processing. Therefore, the investigation of the neural correlates of emotional
      experience requires accounting for such a variable, a matter of an experimental
      challenge. Closing the eyes affects the style of attending to auditory stimuli by
      modifying the perceptual relationship with the environment without changing the
      stimulus itself. In the current study, we used fMRI to characterize the neural
      mediators of such modification on the experience of emotionality in music. We
      assumed that closed eyes position will reveal interplay between different levels
      of neural processing of emotions. More specifically, we focused on the amygdala
      as a central node of the limbic system and on its co-activation with the Locus
      Ceruleus (LC) and Ventral Prefrontal Cortex (VPFC); regions involved in
      processing of, respectively, 'low', visceral-, and 'high', cognitive-related,
      values of emotional stimuli. Fifteen healthy subjects listened to negative and
      neutral music excerpts with eyes closed or open. As expected, behavioral results
      showed that closing the eyes while listening to emotional music resulted in
      enhanced rating of emotionality, specifically of negative music. In
      correspondence, fMRI results showed greater activation in the amygdala when
      subjects listened to the emotional music with eyes closed relative to eyes open.
      More so, by using voxel-based correlation and a dynamic causal model analyses we
      demonstrated that increased amygdala activation to negative music with eyes
      closed led to increased activations in the LC and VPFC. This finding supports a
      system-based model of perceived emotionality in which the amygdala has a central
      role in mediating the effect of context-based processing style by recruiting
      neural operations involved in both visceral (i.e. 'low') and cognitive (i.e.
      'high') related processes of emotions.

PMID- 19603073
TI  - A comprehensive analysis of the structure-function relationship in proteins based
      on local structure similarity.
AB  - BACKGROUND: Sequence similarity to characterized proteins provides testable
      functional hypotheses for less than 50% of the proteins identified by genome
      sequencing projects. With structural genomics it is believed that structural
      similarities may give functional hypotheses for many of the remaining proteins.
      METHODOLOGY/PRINCIPAL FINDINGS: We provide a systematic analysis of the structure
      function relationship in proteins using the novel concept of local descriptors of
      protein structure. A local descriptor is a small substructure of a protein which
      includes both short- and long-range interactions. We employ a library of commonly
      reoccurring local descriptors general enough to assemble most existing protein
      structures. We then model the relationship between these local shapes and Gene
      Ontology using rule-based learning. Our IF-THEN rule model offers legible, high
      resolution descriptions that combine local substructures and is able to
      discriminate functions even for functionally versatile folds such as the
      frequently occurring TIM barrel and Rossmann fold. By evaluating the predictive
      performance of the model, we provide a comprehensive quantification of the
      structure-function relationship based only on local structure similarity. Our
      findings are, among others, that conserved structure is a stronger prerequisite
      for enzymatic activity than for binding specificity, and that structure-based
      predictions complement sequence-based predictions. The model is capable of
      generating correct hypotheses, as confirmed by a literature study, even when no
      significant sequence similarity to characterized proteins exists.
      CONCLUSIONS/SIGNIFICANCE: Our approach offers a new and complete description and
      quantification of the structure-function relationship in proteins. By
      demonstrating how our predictions offer higher sensitivity than using global
      structure, and complement the use of sequence, we show that the presented ideas
      could advance the development of meta-servers in function prediction.

PMID- 19603074
TI  - Unscented Kalman filter for brain-machine interfaces.
AB  - Brain machine interfaces (BMIs) are devices that convert neural signals into
      commands to directly control artificial actuators, such as limb prostheses.
      Previous real-time methods applied to decoding behavioral commands from the
      activity of populations of neurons have generally relied upon linear models of
      neural tuning and were limited in the way they used the abundant statistical
      information contained in the movement profiles of motor tasks. Here, we propose
      an n-th order unscented Kalman filter which implements two key features: (1) use
      of a non-linear (quadratic) model of neural tuning which describes neural
      activity significantly better than commonly-used linear tuning models, and (2)
      augmentation of the movement state variables with a history of n-1 recent states,
      which improves prediction of the desired command even before incorporating neural
      activity information and allows the tuning model to capture relationships between
      neural activity and movement at multiple time offsets simultaneously. This new
      filter was tested in BMI experiments in which rhesus monkeys used their cortical
      activity, recorded through chronically implanted multielectrode arrays, to
      directly control computer cursors. The 10th order unscented Kalman filter
      outperformed the standard Kalman filter and the Wiener filter in both off-line
      reconstruction of movement trajectories and real-time, closed-loop BMI operation.

PMID- 19603075
TI  - Rapid evolution of virulence and drug resistance in the emerging zoonotic
      pathogen Streptococcus suis.
AB  - BACKGROUND: Streptococcus suis is a zoonotic pathogen that infects pigs and can
      occasionally cause serious infections in humans. S. suis infections occur
      sporadically in human Europe and North America, but a recent major outbreak has
      been described in China with high levels of mortality. The mechanisms of S. suis
      pathogenesis in humans and pigs are poorly understood. METHODOLOGY/PRINCIPAL
      FINDINGS: The sequencing of whole genomes of S. suis isolates provides
      opportunities to investigate the genetic basis of infection. Here we describe
      whole genome sequences of three S. suis strains from the same lineage: one from
      European pigs, and two from human cases from China and Vietnam. Comparative
      genomic analysis was used to investigate the variability of these strains. S.
      suis is phylogenetically distinct from other Streptococcus species for which
      genome sequences are currently available. Accordingly, approximately 40% of the
      approximately 2 Mb genome is unique in comparison to other Streptococcus species.
      Finer genomic comparisons within the species showed a high level of sequence
      conservation; virtually all of the genome is common to the S. suis strains. The
      only exceptions are three approximately 90 kb regions, present in the two
      isolates from humans, composed of integrative conjugative elements and
      transposons. Carried in these regions are coding sequences associated with drug
      resistance. In addition, small-scale sequence variation has generated pseudogenes
      in putative virulence and colonization factors. CONCLUSIONS/SIGNIFICANCE: The
      genomic inventories of genetically related S. suis strains, isolated from
      distinct hosts and diseases, exhibit high levels of conservation. However, the
      genomes provide evidence that horizontal gene transfer has contributed to the
      evolution of drug resistance.

PMID- 19603076
TI  - X chromosome inactivation and Xist evolution in a rodent lacking LINE-1 activity.
AB  - Dosage compensation in eutherian mammals occurs by inactivation of one X
      chromosome in females. Silencing of that X chromosome is initiated by Xist, a
      large non-coding RNA, whose coating of the chromosome extends in cis from the X
      inactivation center. LINE-1 (L1) retrotransposons have been implicated as
      possible players for propagation of the Xist signal, but it has remained unclear
      whether they are essential components. We previously identified a group of South
      American rodents in which L1 retrotransposition ceased over 8 million years ago
      and have now determined that at least one species of these rodents, Oryzomys
      palustris, still retains X inactivation. We have also isolated and analyzed the
      majority of the Xist RNA from O. palustris and a sister species retaining L1
      activity, Sigmodon hispidus, to determine if evolution in these sequences has
      left signatures that might suggest a critical role for L1 elements in Xist
      function. Comparison of rates of Xist evolution in the two species fails to
      support L1 involvement, although other explanations are possible. Similarly,
      comparison of known repeats and potential RNA secondary structures reveals no
      major differences with the exception of a new repeat in O. palustris that has
      potential to form new secondary structures.

PMID- 19603077
TI  - The part task of the part-spacing paradigm is not a pure measurement of part
      based information of faces.
AB  - BACKGROUND: Faces are arguably one of the most important object categories
      encountered by human observers, yet they present one of the most difficult
      challenges to both the human and artificial visual systems. A variety of
      experimental paradigms have been developed to study how faces are represented and
      recognized, among which is the part-spacing paradigm. This paradigm is presumed
      to characterize the processing of both the featural and configural information of
      faces, and it has become increasingly popular for testing hypotheses on face
      specificity and in the diagnosis of face perception in cognitive disorders.
      METHODOLOGY/PRINCIPAL FINDINGS: In two experiments we questioned the validity of
      the part task of this paradigm by showing that, in this task, measuring pure
      information about face parts is confounded by the effect of face configuration on
      the perception of those parts. First, we eliminated or reduced contributions from
      face configuration by either rearranging face parts into a non-face configuration
      or by removing the low spatial frequencies of face images. We found that face
      parts were no longer sensitive to inversion, suggesting that the previously
      reported inversion effect observed in the part task was due in fact to the
      presence of face configuration. Second, self-reported prosopagnosic patients who
      were selectively impaired in the holistic processing of faces failed to detect
      part changes when face configurations were presented. When face configurations
      were scrambled, however, their performance was as good as that of normal
      controls. CONCLUSIONS/SIGNIFICANCE: In sum, consistent evidence from testing both
      normal and prosopagnosic subjects suggests the part task of the part-spacing
      paradigm is not an appropriate task for either measuring how face parts alone are
      processed or for providing a valid contrast to the spacing task. Therefore,
      conclusions from previous studies using the part-spacing paradigm may need re
      evaluation with proper paradigms.

PMID- 19603078
TI  - Reef endemism, host specificity and temporal stability in populations of
      symbiotic dinoflagellates from two ecologically dominant Caribbean corals.
AB  - BACKGROUND: The dinoflagellate genus Symbiodinium forms symbioses with numerous
      protistan and invertebrate metazoan hosts. However, few data on symbiont genetic
      structure are available, hindering predictions of how these populations and their
      host associations will fair in the face of global climate change.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, Symbiodinium population structure from two
      of the Caribbean's ecologically dominant scleractinian corals, Montastraea
      faveolata and M. annularis, was examined. Tagged colonies on Florida Keys and
      Bahamian (i.e., Exuma Cays) reefs were sampled from 2003-2005 and their
      Symbiodinium diversity assessed via internal transcribed spacer 2 (ITS2) rDNA and
      three Symbiodinium Clade B-specific microsatellite loci. Generally, the majority
      of host individuals at a site harbored an identical Symbiodinium ITS2 "type" B1
      microsatellite genotype. Notably, symbiont genotypes were largely reef endemic,
      suggesting a near absence of dispersal between populations. Relative to the
      Bahamas, sympatric M. faveolata and M. annularis in the Florida Keys harbored
      unique Symbiodinium populations, implying regional host specificity in these
      relationships. Furthermore, within-colony Symbiodinium population structure
      remained stable through time and environmental perturbation, including a
      prolonged bleaching event in 2005. CONCLUSIONS/SIGNIFICANCE: Taken together, the
      population-level endemism, specificity and stability exhibited by Symbiodinium
      raises concerns about the long-term adaptive capacity and persistence of these
      symbioses in an uncertain future of climate change.

PMID- 19603081
TI  - The Value of Undergraduate Training in Psychological Science.

PMID- 19603080
TI  - Mapping the Micromechanical Properties of Cryo-sectioned Aortic Tissue with
      Scanning Acoustic Microscopy.
AB  - Although the gross mechanical properties of ageing tissues have been extensively
      documented, biological tissues are highly heterogeneous and little is known
      concerning the variation of micro-mechanical properties within tissues. Here, we
      use Scanning Acoustic Microscopy (SAM) to map the acoustic wave speed (a measure
      of stiffness) as a function of distance from the outer adventitial layer of cryo
      sectioned ferret aorta. With a 400 MHz lens, the images of the aorta samples
      matched those obtained following chemical fixation and staining of sections which
      were viewed with fluorescence microscopy. Quantitative analysis was conducted
      with a frequency scanning or V(f) technique by imaging the tissue from 960 MHz to
      1.1 GHz. Undulating acoustic wave speed (stiffness) distributions corresponded
      with elastic fibre locations in the tissue; there was a decrease in wave speed of
      around 40 ms(-1) from the adventitia (outer layer) to the intima (innermost).

PMID- 19603079
TI  - Influence of smoking on colonic gene expression profile in Crohn's disease.
AB  - BACKGROUND: The development and course of Crohn's disease (CD) is related to both
      genetic and environmental factors. Smoking has been found to exacerbate the
      course of CD by increasing the risk of developing fistulas and strictures as well
      as the need for surgery, possibly because of an interaction between smoking or
      nicotine on macrophage function and the intestinal microvasculature. Several
      genes are involved in the pathogenesis of CD, and in this study the gene
      expression differences of the descending colonic mucosa were investigated in CD
      (smokers or never smokers) and controls (smokers or never smokers). AIM: To
      identify any difference in gene expression of the descending colonic mucosa
      between smoking and never-smoking CD patients (and controls) by determining
      genetic expression profiles from microarray analysis. METHODS: Fifty-seven
      specimens were obtained by routine colonoscopy from the included material: CD
      smokers (n = 28) or never-smokers (n = 14) as compared to fifteen healthy
      controls (8 smokers and 7 never-smokers). RNA was isolated and gene expression
      assessed with Affymetrix GeneChip Human Genome U133 Plus 2.0. Data were analyzed
      by principal component analysis (PCA), Wilcoxon rank sum test and multiple linear
      regressions. Real-time (RT) PCR was subsequently applied to verify microarray
      results. RESULTS: The PCA analysis showed no intrinsic clustering of smokers
      versus never-smokers. However, when Wilcoxon rank sum test corrected with Q
      values were performed, six known genes were significantly expressed differently
      in the inflamed CD smokers as compared to the inflamed CD never-smokers: ring
      finger protein 138 (RNF138), metalothionein 2A (MT2A) and six transmembrane
      epithelial antigen of the prostate 3 (STEAP3), SA hypertension-associated
      homolog, PGM2L1 and KCNJ2. The subsequent RT-PCR-analyses verified, however, that
      only RNF138, MT2A and STEAP3 were significantly up-regulated in CD smokers in
      specimens with inflammatory activity of the descending colon. CONCLUSIONS: The
      present study demonstrates that the genes, RNF138, MT2A, and STEAP3 are
      differently expressed in the inflamed descending colon of smoking versus never
      smoking CD patients, which might be of relevance for the poorer clinical course
      among CD smokers. Many gastroenterologists are still not totally aware of the
      benefits of smoking cessation in relation to CD, and do not put much effort into
      getting the patients to quit, therefore more information on the negative effects
      of smoking, seems warranted.

PMID- 19603084
TI  - Discussion of "Sure Independence Screening for Ultra-High Dimensional Feature
      Space.

PMID- 19603083
TI  - Exploiting Acoustic and Syntactic Features for Automatic Prosody Labeling in a
      Maximum Entropy Framework.
AB  - In this paper, we describe a maximum entropy-based automatic prosody labeling
      framework that exploits both language and speech information. We apply the
      proposed framework to both prominence and phrase structure detection within the
      Tones and Break Indices (ToBI) annotation scheme. Our framework utilizes novel
      syntactic features in the form of supertags and a quantized acoustic-prosodic
      feature representation that is similar to linear parameterizations of the
      prosodic contour. The proposed model is trained discriminatively and is robust in
      the selection of appropriate features for the task of prosody detection. The
      proposed maximum entropy acoustic-syntactic model achieves pitch accent and
      boundary tone detection accuracies of 86.0% and 93.1% on the Boston University
      Radio News corpus, and, 79.8% and 90.3% on the Boston Directions corpus. The
      phrase structure detection through prosodic break index labeling provides
      accuracies of 84% and 87% on the two corpora, respectively. The reported results
      are significantly better than previously reported results and demonstrate the
      strength of maximum entropy model in jointly modeling simple lexical, syntactic,
      and acoustic features for automatic prosody labeling.

PMID- 19603082
TI  - Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer
      supporting factors leading to rapid STAT3 activation.
AB  - Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach,
      and recent studies have demonstrated bacterial contamination of primary and
      metastatic OSCC. Increasing concentrations of inflammatory products, such as
      interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with,
      and contribute to, cancer progression, but their regulation in OSCC is poorly
      understood. We hypothesized that monocyte-lineage cells and bacterial
      contamination may contribute important inflammatory products that can support
      OSCC progression. We found that relative to non-specific chronic mucositis, oral
      carcinoma-in-situ/superficially-invasive OSCC contained more monocyte-lineage
      cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial
      contamination, and evaluated the effects of oral and oropharyngeal (O)SCC
      monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and
      VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production,
      and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF
      occasionally, while LPS-OSCC-monocyte interactions were always strongly
      stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete
      monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6
      and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705
      STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC
      lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC
      monocyte co-cultures always rapidly and strongly activated STAT3, which was
      partly due to IL-6. We conclude that monocytes and microbial contamination have
      the potential to contribute to OSCC progression, as STAT3 activation in OSCC
      cells depends on soluble factors, which are consistently available through LPS
      OSCC-monocyte interactions.

PMID- 19603086
TI  - Stature and status: Height, ability, and labor market outcomes.
AB  - The well-known association between height and earnings is often thought to
      reflect factors such as self esteem, social dominance, and discrimination. We
      offer a simpler explanation: height is positively associated with cognitive
      ability, which is rewarded in the labor market. Using data from the US and the
      UK, we show that taller children have higher average cognitive test scores, and
      that these test scores explain a large portion of the height premium in earnings.
      Children who have higher test scores also experience earlier adolescent growth
      spurts, so that height in adolescence serves as a marker of cognitive ability.

PMID- 19603085
TI  - Enantioselective Synthesis of Hydrobenzofuranones Using an Asymmetric
      Desymmetrizing Intramolecular Stetter Reaction of Cyclohexadienones.
AB  - A series of cyclohexadienones were synthesized by dearomatization of phenols
      followed by Dess-Martin oxidation. Asymmetric intramolecular Stetter reactions of
      these substrates provide hydrobenzofuranones in good to excellent yields and
      excellent stereoselectivities. Up to three stereocenters as well as quaternary
      stereocenter are formed from polysubstituted substrates. A scale up experiment
      demonstrates the utility of this transformation.

PMID- 19603088
TI  - Flexible distributions for triple-goal estimates in two-stage hierarchical
      models.
AB  - Performance evaluations often aim to achieve goals such as obtaining estimates of
      unit-specific means, ranks, and the distribution of unit-specific parameters. The
      Bayesian approach provides a powerful way to structure models for achieving these
      goals. While no single estimate can be optimal for achieving all three
      inferential goals, the communication and credibility of results will be enhanced
      by reporting a single estimate that performs well for all three. Triple goal
      estimates [Shen and Louis, 1998. Triple-goal estimates in two-stage hierarchical
      models. J. Roy. Statist. Soc. Ser. B 60, 455-471] have this performance and are
      appealing for performance evaluations. Because triple-goal estimates rely more
      heavily on the entire distribution than do posterior means, they are more
      sensitive to misspecification of the population distribution and we present
      various strategies to robustify triple-goal estimates by using nonparametric
      distributions. We evaluate performance based on the correctness and efficiency of
      the robustified estimates under several scenarios and compare empirical Bayes and
      fully Bayesian approaches to model the population distribution. We find that when
      data are quite informative, conclusions are robust to model misspecification.
      However, with less information in the data, conclusions can be quite sensitive to
      the choice of population distribution. Generally, use of a nonparametric
      distribution pays very little in efficiency when a parametric population
      distribution is valid, but successfully protects against model misspecification.

PMID- 19603087
TI  - Domino Heck-Aza-Michael Reactions: A One-Pot, Sequential Three-Component Approach
      to 1,1-Dioxido-1,2-benzisothiazoline-3-acetic Acid.
AB  - The development of a new method for the synthesis of 1,1-dioxido-1,2
      benzisothiazoline-3-acetic acid by a domino process is reported whereby a
      classical Heck reaction is coupled to an intramolecular aza-Michael reaction.
      Ultimately, this method has been expanded to a one-pot, sequential three
      component protocol to generate diverse benzofused gamma-sultams from a range of
      commercially available alpha-bromobenzenesulfonyl chlorides, amines and Michael
      acceptors.

PMID- 19603098
TI  - Cardiac health diagnosis using higher order spectra and support vector machine.
AB  - The Electrocardiogram (ECG) is an important bio-signal representing the sum total
      of millions of cardiac cell depolarization potentials. It contains important
      insight into the state of health and nature of the disease afflicting the heart.
      Heart rate variability (HRV) refers to the regulation of the sinoatrial node, the
      natural pacemaker of the heart by the sympathetic and parasympathetic branches of
      the autonomic nervous system. The HRV signal can be used as a base signal to
      observe the heart's functioning. These signals are non-linear and non-stationary
      in nature. So, higher order spectral (HOS) analysis, which is more suitable for
      non-linear systems and is robust to noise, was used. An automated intelligent
      system for the identification of cardiac health is very useful in healthcare
      technology. In this work, we have extracted seven features from the heart rate
      signals using HOS and fed them to a support vector machine (SVM) for
      classification. Our performance evaluation protocol uses 330 subjects consisting
      of five different kinds of cardiac disease conditions. We demonstrate a
      sensitivity of 90% for the classifier with a specificity of 87.93%. Our system is
      ready to run on larger data sets.

PMID- 19603099
TI  - Progesterone with vitamin D affords better neuroprotection against excitotoxicity
      in cultured cortical neurons than progesterone alone.
AB  - Because the complex heterogeneity of traumatic brain injury (TBI) is believed by
      many to be a major reason for the failed clinical trials of monotherapies,
      combining two (or more) drugs with some potentially different mechanisms of
      action may produce better effects than administering those agents individually.
      In this study, we investigated whether combinatorial treatment with progesterone
      (PROG) and 1,25-dihydroxyvitamin D(3) hormone (VDH) would produce better
      neuroprotection than PROG alone following excitotoxic neuronal injury in vitro.
      E18 rat primary cortical neurons were pretreated with various concentrations of
      PROG and VDH separately or in combination for 24 h and then exposed to glutamate
      (0.5 micromol/L) for the next 24 h. Lactate dehydrogenase (LDH) release and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assays
      were used to measure cell death. Both PROG and VDH significantly (P < 0.001)
      reduced neuronal loss when tested independently. Primary cortical cultures
      treated with VDH exhibited a U-shaped concentration-response curve. PROG at 20
      micromol/L and VDH at 100 nmol/L concentrations were the most neuroprotective.
      When the drugs were combined, the "best" doses of PROG (20 micromol/L) and VDH
      (100 nmol/L), used individually, did not show substantial efficacy; rather, the
      lower dose of VDH (20 nmol/L) was most effective when used in combination with
      PROG (P < 0.01). We also examined the effect of combinatorial treatment on
      mitogen-activated protein kinase (MAPK) activation as a potential neuroprotective
      mechanism and observed that PROG and VDH activated MAPK alone and in combination.
      Interestingly, the best combination dose of PROG and VDH (20 micromol/L and 20
      nmol/L, respectively), as observed in cell death assays (LDH and MTT), resulted
      in increased MAPK activation compared with either the most neuroprotective
      concentration of individual PROG (20 micromol/L) and VDH (100 nmol/L) or the
      combination of these individual best doses. Such interactions must be considered
      in planning individualized combinatorial therapies. In conclusion, the findings
      of the present study can be taken to suggest that VDH warrants study as a
      potential partner for combination therapy with PROG.

PMID- 19603096
TI  - An analysis of growth, differentiation and apoptosis genes with risk of renal
      cancer.
AB  - We conducted a case-control study of renal cancer (987 cases and 1298 controls)
      in Central and Eastern Europe and analyzed genomic DNA for 319 tagging single
      nucleotide polymorphisms (SNPs) in 21 genes involved in cellular growth,
      differentiation and apoptosis using an Illumina Oligo Pool All (OPA). A haplotype
      based method (sliding window analysis of consecutive SNPs) was used to identify
      chromosome regions of interest that remained significant at a false discovery
      rate of 10%. Subsequently, risk estimates were generated for regions with a high
      level of signal and individual SNPs by unconditional logistic regression
      adjusting for age, gender and study center. Three regions containing genes
      associated with renal cancer were identified: caspase 1/5/4/12(CASP 1/5/4/12),
      epidermal growth factor receptor (EGFR), and insulin-like growth factor binding
      protein-3 (IGFBP3). We observed that individuals with CASP1/5/4/12 haplotype
      (spanning area upstream of CASP1 through exon 2 of CASP5) GGGCTCAGT were at
      higher risk of renal cancer compared to individuals with the most common
      haplotype (OR:1.40, 95% CI:1.10-1.78, p-value = 0.007). Analysis of EGFR revealed
      three strong signals within intron 1, particularly a region centered around
      rs759158 with a global p = 0.006 (GGG: OR:1.26, 95% CI:1.04-1.53 and ATG:
      OR:1.55, 95% CI:1.14-2.11). A region in IGFBP3 was also associated with increased
      risk (global p = 0.04). In addition, the number of statistically significant (p
      value<0.05) SNP associations observed within these three genes was higher than
      would be expected by chance on a gene level. To our knowledge, this is the first
      study to evaluate these genes in relation to renal cancer and there is need to
      replicate and extend our findings. The specific regions associated with risk may
      have particular relevance for gene function and/or carcinogenesis. In conclusion,
      our evaluation has identified common genetic variants in CASP1, CASP5, EGFR, and
      IGFBP3 that could be associated with renal cancer risk.

PMID- 19603100
TI  - CD151 gene delivery after myocardial infarction promotes functional
      neovascularization and activates FAK signaling.
AB  - Our previous studies showed that tetraspanin CD151 promotes neovascularization in
      rat hindlimb and myocardial ischemia models. This study is to assess whether
      CD151 induces arteriogenesis and promotes functional neovascularization in a pig
      myocardial infarction model, and to determine the signaling pathways involved.
      CD151 cDNA and antiCD151 sequence were constructed into a recombinant adeno
      associated virus (rAAV) vector. All 26 pigs used either were subjected to
      coronary artery ligation or did not undergo surgery. Eight wks after viral
      administration, the expression of CD151 protein was measured by Western blot. The
      densities of capillaries and arterioles were determined using
      immunohistochemistry. Regional myocardial perfusion and other myocardial
      functions were evaluated by (13)N-labeled NH(3) positron emission computed
      tomography ((13)N-NH(3) PET) and echocardiography. Western blot was performed for
      assessing the signaling mechanisms. Overexpression of CD151 markedly increased
      the densities of capillaries and arterioles, significantly enhanced the regional
      myocardial perfusion, reduced myocardial ischemia, and improved the myocardial
      contraction, wall motion, and wall thickness. Conversely, antiCD151 gene delivery
      reversed the above changes. In addition, CD151 activated focal adhesion kinase
      (FAK), extracellular signal-regulated kinase (ERK), c-Jun N-teminal kinase (JNK),
      phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and endothelial
      nitric-oxide synthase (eNOS), and increased nitric oxide (NO) level. These
      findings demonstrate a robust role of CD151 in inducing and/or upregulating
      neovascularization. CD151-dependent neovascularization correlates with the
      activations of FAK, mitogen activated protein kinases (MAPKs), and PI3K
      signaling, suggesting that CD151 may promote neovascularization via MAPKs and
      PI3K pathways.

PMID- 19603101
TI  - Role of E2F1-cyclin E1-cyclin E2 circuit in human coronary smooth muscle cell
      proliferation and therapeutic potential of its downregulation by siRNAs.
AB  - Aberrant coronary vascular smooth muscle cell (CSMC) proliferation is a pivotal
      event underlying intimal hyperplasia, a phenomenon impairing the long-term
      efficacy of bypass surgery and angioplasty procedures. Consequently research has
      become focused on efforts to identify molecules that are able to control CSMC
      proliferation. We investigated downregulation of CSMC growth by small interfering
      RNAs (siRNAs) targeted against E2F1, cyclin E1, and cyclin E2 genes, whose
      contribution to CSMC proliferation is only now being recognized. Chemically
      synthesized siRNAs were delivered by two different transfection reagents to
      asynchronous and synchronous growing human CSMCs cultivated either in normo- or
      hyperglycemic conditions. The depletion of each of the three target genes
      affected the expression of the other two genes, demonstrating a close regulatory
      control. The clearest effects associated with the inhibition of the E2F1-cyclin
      E1/E2 circuit were the reduction in the phosphorylation levels of the
      retinoblastoma protein pRB and a decrease in the amount of cyclin A2. At the
      phenotypic level the downmodulation of CSMC proliferation resulted in a decrease
      of S phase matched by an increase of G1-G0 phase cell amounts. The
      antiproliferative effect was cell-donor and transfectant independent, reversible,
      and effective in asynchronous and synchronous growing CSMCs. Importantly, it was
      also evident in hyperglycemia, a condition that underlies diabetes. No
      significant aspecific cytotoxicity was observed. Our data demonstrate the
      interrelation among E2F1-cyclin E1-cyclin E2 and the pivotal role this circuit
      exerts in CSMC proliferation. Additionally, our work validates the concept of
      utilizing anti-E2F1-cyclin E1-cyclin E2 siRNAs to develop a potential novel
      therapy to control intimal hyperplasia.

PMID- 19603103
TI  - Severe burn-induced endoplasmic reticulum stress and hepatic damage in mice.
AB  - Severe burn injury results in liver dysfunction and damage, with subsequent
      metabolic derangements contributing to patient morbidity and mortality. On a
      cellular level, significant postburn hepatocyte apoptosis occurs and likely
      contributes to liver dysfunction. However, the underlying mechanisms of
      hepatocyte apoptosis are poorly understood. The endoplasmic reticulum (ER) stress
      response/unfolded protein response (UPR) pathway can lead to hepatocyte apoptosis
      under conditions of liver dysfunction. Thus, we hypothesized that ER stress/UPR
      may mediate hepatic dysfunction in response to burn injury. We investigated the
      temporal activation of hepatic ER stress in mice after a severe burn injury. Mice
      received a scald burn over 35% of their body surface and were killed at 1, 7, 14,
      and 21 d postburn. We found that severe burn induces hepatocyte apoptosis as
      indicated by increased caspase-3 activity (P < 0.05). Serum albumin levels
      decreased postburn and remained lowered for up to 21 d, indicating that
      constitutive secretory protein synthesis was reduced. Significantly, upregulation
      of the ER stress markers glucose-related protein 78 (GRP78)/BIP, protein
      disulfide isomerase (PDI), p-protein kinase R-like endoplasmic reticulum kinase
      (p-PERK), and inositol-requiring enzyme 1alpha (IRE-1alpha) were found beginning
      1 d postburn (P < 0.05) and persisted up to 21 d postburn (P < 0.05). Hepatic ER
      stress induced by burn injury was associated with compensatory upregulation of
      the calcium chaperone/storage proteins calnexin and calreticulin (P < 0.05),
      suggesting that ER calcium store depletion was the primary trigger for induction
      of the ER stress response. In summary, thermal injury in mice causes long-term
      adaptive and deleterious hepatic function alterations characterized by
      significant upregulation of the ER stress response.

PMID- 19603104
TI  - Osteopontin is associated with increased arterial stiffness in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) patients are characterized by increased arterial
      stiffness, an independent predictor of cardiovascular risk. It has been suggested
      that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have
      vascular effects. To study a possible relationship between OPN and arterial
      stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69
      patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls.
      Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were
      assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93,
      range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1
      9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log
      CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment
      Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total
      cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P <
      0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA
      (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but
      significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s).
      Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It
      also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P <
      0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r(2) =
      0.36), including confounders, log-OPN remained a significant predictor (P < 0.05)
      of PWV in RA. Elevated plasma OPN levels are associated with increased arterial
      stiffness in RA patients, suggesting that this protein might represent a bridge
      protein between inflammation and the consequent joint damage and cardiovascular
      risk in RA patients.

PMID- 19603110
TI  - Mirror image phage display--a method to generate D-peptide ligands for use in
      diagnostic or therapeutical applications.
AB  - Mirror image phage display is a straightforward approach to identify new
      potentially therapeutically active D-enantiomeric peptides. Such D-peptides are
      more resistant to proteolytic degradation compared to L-peptides. In this review,
      several examples of mirror image phage display derived D-peptides with
      therapeutical potential are introduced and discussed.

PMID- 19603111
TI  - Locked nucleic acid nucleoside triphosphates and polymerases: on the way towards
      evolution of LNA aptamers.
AB  - Among numerous nucleic acid analogs reported in the past decades, locked nucleic
      acid (LNA) has received substantial attention and has become a significant tool
      within chemical biology disciplines like molecular biology research, diagnostics
      and therapeutic development. However, despite their obvious structurally unique
      properties, LNA-based aptamers for diagnostic and therapeutic applications remain
      largely unexplored. Future evolution of LNA oligonucleotide aptamers will depend
      on scientific breakthroughs relating to enzymatic polymerization using LNA
      nucleoside triphosphates as substrates. Herein, we highlight recent developments
      in this direction using various polymerases.

PMID- 19603106
TI  - Intratracheal delivery of CX3CL1-expressing mesenchymal stem cells to multiple
      lung tumors.
AB  - The lung is one of the organs to which cancers from solid tumors frequently
      metastasize. Multiple tumors in the lung are usually treated by systemic
      chemotherapy because of the lack of efficient methods of targeting antitumor
      agents to the lung. Although intratracheal administration is an ideal route for
      targeting multiple lung tumors, antitumor agents are often harmful to the organ
      or induce inflammation. Mesenchymal stem cells (MSCs), nonhematopoietic stem
      cells capable of differentiating into various mesoderm-type cells, have a
      propensity to migrate to and proliferate in tumor tissues after systemic
      administration. We intratracheally injected MSCs expressing CX3CL1 (MSC/RGDFKN)
      into the lung of lung tumor-bearing mice with multiple metastases of C26 or Lewis
      lung carcinoma (LLC). Antitumor effects were evaluated by counting the number of
      lung metastases and survival. We demonstrated the tropism of mouse MSCs to lung
      tumor tissues after intratracheal administration of GFP-positive MSCs.
      Intratracheal injection of MSC/RGDFKN strongly inhibited growth of lung
      metastases of C26 or LLC, and thus prolonged survival. Intratracheal injection of
      MSC/RGDFKN did not induce an inflammatory reaction in the lung. These results
      suggest that MSCs expressing antitumor agents can be delivered intratracheally
      into multiple lung tumor tissues without causing inflammation.

PMID- 19603105
TI  - The inverse association between cardiorespiratory fitness and C-reactive protein
      is mediated by autonomic function: a possible role of the cholinergic
      antiinflammatory pathway.
AB  - Although studies have shown an inverse association between cardiorespiratory
      fitness (CRF) and C-reactive protein (CRP) levels, the underlying mechanisms are
      not fully understood. There is emerging evidence that autonomic nervous system
      function is related to CRP levels. Because high CRF is related to improved
      autonomic function, we hypothesized that the association between high CRF and low
      CRP levels would be affected by autonomic nervous system function. Cross
      sectional analyses were conducted on 2,456 asymptomatic men who participated in a
      medical screening program. Fasting blood samples for cardiovascular disease risk
      factors were analyzed, and CRF was measured by maximal exercise treadmill test
      with expired gas analysis. We used an index of cardiac autonomic imbalance
      defined as the ratio of resting heart rate to 1 min of heart rate recovery after
      exercise (RHR/HRR). CRF was significantly correlated with CRP (r = -0.16, P <
      0.05), and RHR/HRR (r = -0.48, P < 0.05), while RHR/HRR was significantly
      correlated with CRP (r = 0.25, P < 0.05). In multivariable linear regression
      models that adjusted for age, body mass index, smoking, disease status,
      medications, lipid profiles, glucose, and systolic blood pressure, CRF was
      inversely associated with CRP (beta = -0.09, P < 0.05). However, this
      relationship was no longer significant after adjusting for RHR/HRR in a
      multivariable linear regression model (beta = -0.03, P = 0.29). These results
      suggest that autonomic nervous system function significantly affects the
      relationship between CRF and inflammation in middle-aged men. Thus, physical
      activity or exercise training may favorably affect the cholinergic
      antiinflammatory pathway, but additional research is needed to confirm this
      finding.

PMID- 19603112
TI  - The complex biology of autocrine motility factor/phosphoglucose isomerase
      (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase.
AB  - Phosphoglucose isomerase (PGI) is a glycolytic enzyme that exhibits a dual
      function as an extracellular cytokine, under the name autocrine motility factor
      (AMF). Its cell surface receptor, gp78/AMFR, is also localized to the endoplasmic
      reticulum where it functions as an E3 ubiquitin ligase. Expression of both
      AMF/PGI and gp78/AMFR is associated with cancer and, in this review, we will
      discuss various aspects of the biology of this ligand-receptor complex and its
      role in tumor progression.

PMID- 19603102
TI  - Regulatory NK-cell functions in inflammation and autoimmunity.
AB  - Natural killer (NK) cells were viewed traditionally as cytotoxic effector cells
      whose rapid killing of infected and transformed cells without preactivation
      provides a first line of defense prior to the initiation of an adaptive immune
      response against infection and tumor development. However, it has become clear
      that NK cells interact with various components of the immune system, and
      therefore have the potential to function as regulatory cells. While NK cells can
      assist in dendritic cell (DC) maturation and T-cell polarization, increasing
      evidence indicates that NK cells can also prevent and limit adaptive (auto)
      immune responses via killing of autologous myeloid and lymphoid cells.
      Investigating immunoregulatory NK-cell functions might generate exciting insights
      into the reciprocal regulation between NK-cell-mediated innate immunity and
      adaptive immune responses, improve our capacity to monitor these cells as
      surrogate markers for disease activity and treatment responses in autoimmune
      diseases, and, perhaps, provide new prospects for NK cell-directed therapies.

PMID- 19603114
TI  - Biomimetic approaches for studying membrane processes.
AB  - This short review focuses on recent innovative systems and experimental
      approaches designed to investigate membrane processes and biomolecular
      interactions associated with membranes. Our emphasis is on "biomimetics" which
      reflects the significance and contributions of the chemistry/biology interface in
      addressing complex biological questions. We have not limited this review to
      discussion of new "sensors" or "assays"per se, but rather we tried to review new
      concepts employed for analysis of membrane processes.

PMID- 19603115
TI  - Targeting lectin activity into inclusion bodies for the characterisation of
      glycoproteins.
AB  - Physiological aggregation of lectin functional domains into active inclusion
      bodies would provide a simple tool for glycocode reading by well-established
      agglutination assays.

PMID- 19603116
TI  - Synthesis and cellular uptake properties of guanidine-containing molecular
      transporters built on the sucrose scaffold.
AB  - Novel sucrose-based G7 molecular transporters show different patterns of
      intracellular localization depending on the nature of the linker chains as well
      as the fluorescent dyes.

PMID- 19603113
TI  - Searching for interesting channels: pairing selection and molecular evolution
      methods to study ion channel structure and function.
AB  - The pairing of selection and screening methods with randomly mutated libraries
      can be an exceptionally powerful means for probing the functions of biological
      molecules and for developing novel regents from random libraries of peptides and
      oligonucleotides. The use of such approaches is beginning to permeate the ion
      channel field where they are being deployed to uncover fundamental aspects about
      ion channel structure and gating, small molecule-channel interactions, and the
      development of novel agents to control channel activity.

PMID- 19603117
TI  - Modification and optimization of organosilica microspheres for peptide synthesis
      and microsphere-based immunoassays.
AB  - A new generation of optically encoded organosilica microspheres, suitable for
      both solid phase synthesis and multiplexed microsphere-based assays, has recently
      been described. One of the challenges of producing this type of dual-purpose
      solid support is that the particles must maintain their morphology as well as
      their encoding during exposure to the solvents used for solid phase synthesis. In
      this article, organosilica microspheres are subjected to ammonia treatment
      methods for enhancing the condensation of the silica matrix and their subsequent
      resilience toward organic solvents and peptide synthesis reagents is described.
      The instability of the untreated supports toward organic synthesis reagents was
      found to be associated with the swelling and permeability of these microspheres
      in organic solvents. Post-synthesis ammonia treatment resulted in reduced
      permeability, as demonstrated by dye uptake studies. The treated microspheres
      exhibited enhanced stability against organic synthesis conditions and were
      characterized via a variety of techniques including electron microscopy, (29)Si
      nuclear magnetic resonance (NMR) and optical microscopy. The ammonia-treated
      supports were subjected to an Fmoc peptide synthesis procedure and successfully
      applied in a model microsphere-based flow cytometric immunoassay.

PMID- 19603107
TI  - The hepatic response to thermal injury: is the liver important for postburn
      outcomes?
AB  - Thermal injury produces a profound hypermetabolic and hypercatabolic stress
      response characterized by increased endogenous glucose production via
      gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the
      central body organ involved in these metabolic responses. It is suggested that
      the liver, with its metabolic, inflammatory, immune, and acute phase functions,
      plays a pivotal role in patient survival and recovery by modulating multiple
      pathways following thermal injury. Studies have evaluated the role and function
      of the liver during the postburn response and showed that liver integrity and
      function are essential for survival, and that hepatic acute phase proteins are
      strong predictors for postburn survival. This review discusses these studies and
      delineates the pivotal role of the liver in patients following severe thermal
      injury.

PMID- 19603118
TI  - The role of membrane microdomains in shaping beta2-adrenergic receptor-mediated
      cAMP dynamics.
AB  - Recently, membrane rafts and caveolae have received much attention for their role
      as signaling platforms, particularly due to their involvement in the pathogenesis
      of a number of diseases, including HIV as well as neurological and cardiovascular
      conditions. Signaling mediated by the beta-adrenergic receptor (beta-AR), a
      member of the large family of G-protein coupled receptors (GPCRs) that transduce
      extracellular messages via the ubiquitous second messenger, cAMP, has been a
      focus of raft studies since multiple components of the pathway are
      compartmentalized by these membrane microdomains. However, how these membrane
      rafts behave and regulate signaling dynamics in a cellular context is poorly
      understood. Here, we describe a live-cell assay based on single-cell, real-time
      fluorescence imaging, via an improved FRET-based cAMP biosensor, to monitor raft
      regulation of second messenger dynamics. Upon cholesterol depletion with methyl
      beta-cyclodextrin (MbetaCD), beta(2)-AR-mediated cAMP accumulation was enhanced
      and prolonged in HEK-293 cells, demonstrating that membrane raft integrity helps
      shape beta-AR signaling. Single-cell imaging in parallel with fractionation
      studies reveal that the enhancement and change of dynamics are mediated by the
      receptor and correlated with its redistribution. Finally, the effect of
      cholesterol depletion is receptor-type specific as MbetaCD treatment did not show
      the same effect when the raft-excluded prostaglandin E receptor was stimulated.
      This study highlights the potential of a live-cell, real-time imaging assay for
      studying membrane rafts, including high sensitivity and spatiotemporal
      resolution, to achieve a better understanding of the nuances of membrane
      microdomains in both healthy and diseased states.

PMID- 19603119
TI  - Filling the gap in LNA antisense oligo gapmers: the effects of unlocked nucleic
      acid (UNA) and 4'-C-hydroxymethyl-DNA modifications on RNase H recruitment and
      efficacy of an LNA gapmer.
AB  - Stability against nucleases, affinity for the targeted mRNA and the ability to
      recruit RNase H are prerequisites for antisense oligonucleotide (AON)
      applications where gene expression knockdown is required. Typically chimeric
      gapmer AON designs are used with a central continuous stretch of RNase H
      recruiting nucleotides (e.g. phosphorothioate DNA), flanked by affinity and
      stability-enhancing modified nucleotides. However, many types of nucleotide
      modifications in the central DNA gap can disturb RNase H function. Here we
      present studies into two different types of nucleotide modifications, a flexible
      acyclic RNA analog named unlocked nucleic acid (UNA) and 4'-C-hydroxymethyl-DNA
      in the gap of an LNA (locked nucleic acid) flanked gapmer. We compared the
      efficacy of mRNA degradation by the gap modified LNA antisense gapmers in cell
      free assays and cultured cells. This study shows that both UNA and 4'-C
      hydroxymethyl-DNA gap insertions are compatible with RNase H activity when used
      sparingly. However, multiple 4'-C-hydroxymethyl-DNA modifications are better
      tolerated by RNase H than multiple UNA modifications in the gap. Furthermore,
      this report shows that LNA gapmer AONs with multiple 4'-C-hydroxymethyl-DNA
      moieties in the gap can mediate target knockdown in vivo.

PMID- 19603120
TI  - Predicting the multi-modal binding propensity of small molecules: towards an
      understanding of drug promiscuity.
AB  - Drug promiscuity is one of the key issues in current drug development. Many
      famous drugs have turned out to behave unexpectedly due to their propensity to
      bind to multiple targets. One of the primary reasons for this promiscuity is that
      drugs bind to multiple distinctive target environments, a feature that we call
      multi-modal binding. Accordingly, investigations into whether multi-modal binding
      propensities can be predicted, and if so, whether the features determining this
      behavior can be found, would be an important advance. In this study, we have
      developed a structure-based classifier that predicts whether small molecules will
      bind to multiple distinct binding sites. The binding sites for all ligands in the
      Protein Data Bank (PDB) were clustered by binding site similarity, and the
      ligands that bind to many dissimilar binding sites were identified as multi-modal
      binding ligands. The mono-binding ligands were also collected, and the
      classifiers were built using various machine-learning algorithms. A 10-fold cross
      validation procedure showed 70-85% accuracy depending on the choice of machine
      learning algorithm, and the different definitions used to identify multi-modal
      binding ligands. In addition, a quantified importance measurement for global and
      local descriptors was also provided, which suggests that the local features are
      more likely to have an effect on multi-modal binding than the global ones. The
      interpretable global and local descriptors were also ranked by their importance.
      To test the classifier on real examples, several test sets including well-known
      promiscuous drugs were collected by a literature and database search. Despite the
      difficulty in constructing appropriate testable sets, the classifier showed
      reasonable results that were consistent with existing information on drug
      behavior. Finally, a test on natural enzyme substrates and artificial drugs
      suggests that the natural compounds tend to exhibit a broader range of multi
      modal binding than the drugs.

PMID- 19603121
TI  - Genome-wide survey of microRNA-transcription factor feed-forward regulatory
      circuits in human.
AB  - In this work, we describe a computational framework for the genome-wide
      identification and characterization of mixed transcriptional/post-transcriptional
      regulatory circuits in humans. We concentrated in particular on feed-forward
      loops (FFL), in which a master transcription factor regulates a microRNA, and
      together with it, a set of joint target protein coding genes. The circuits were
      assembled with a two step procedure. We first constructed separately the
      transcriptional and post-transcriptional components of the human regulatory
      network by looking for conserved over-represented motifs in human and mouse
      promoters, and 3'-UTRs. Then, we combined the two subnetworks looking for mixed
      feed-forward regulatory interactions, finding a total of 638 putative (merged)
      FFLs. In order to investigate their biological relevance, we filtered these
      circuits using three selection criteria: (I) GeneOntology enrichment among the
      joint targets of the FFL, (II) independent computational evidence for the
      regulatory interactions of the FFL, extracted from external databases, and (III)
      relevance of the FFL in cancer. Most of the selected FFLs seem to be involved in
      various aspects of organism development and differentiation. We finally discuss a
      few of the most interesting cases in detail.

PMID- 19603122
TI  - A metabonomic study of hepatitis B-induced liver cirrhosis and hepatocellular
      carcinoma by using RP-LC and HILIC coupled with mass spectrometry.
AB  - Liver cirrhosis and hepatocellular carcinoma (HCC) are fatal sequelaes of chronic
      hepatitis B in China. The sera from HCC and cirrhosis were profiled by rapid
      resolution liquid chromatography coupled with quadrupole time-of-flight (Q-TOF)
      mass spectrometry. Reversed-phased (RP) liquid chromatography and hydrophilic
      interaction chromatography (HILIC) were used for the data acquisition. The
      normalized and combined data were handled by chemometric analysis, and the
      combination proved to be effective and reliable for the orthogonal projection to
      latent structures (OPLS) analysis. Metabonomic profiles and the potential
      biomarkers were found based on the OPLS models. Shared and unique structure (SUS)
      plots were used for the evaluation of the potential biomarkers. Glycocholic acid,
      glycochenodeoxycholic acid, taurocholic acid and taurochenodesoxycholic acid were
      found to be potential biomarkers related to liver cirrhosis, while
      dihydrosphingosine and phytosphingosine were potential diagnostic biomarkers of
      HCC. The other identified metabolites were considered as common potential
      biomarkers for the two liver diseases. Correlation networks based on these
      metabolites were also built for the systemic understanding of these diseases and
      the possible biological implications are discussed. This metabonomic approach may
      provide insight into discovery and identification of new diagnostic biomarkers
      for liver cancer and associated diseases.

PMID- 19603125
TI  - The effect of pulmonary rehabilitation on perceptions of breathlessness and
      activity in COPD patients: a qualitative study.
AB  - AIM: The aim of this study was to explore, using qualitative research methods,
      how pulmonary rehabilitation (PR) programmes affect the experience of activity
      and breathlessness of people with COPD. METHODS: A qualitative, interview-based
      approach was employed. Participants were interviewed pre- and post-PR. Data were
      analysed using systematic strategies informed by grounded theory methods.
      RESULTS: Nine participants (three female) took part. A change in participants'
      perception of breathlessness and lessening of fear of activity were the main
      themes identified. PR appeared to impact on the experience of physical social
      activities, allowing participants to overcome feelings of social isolation.
      CONCLUSIONS: Prior to PR, participants associated activities with breathlessness
      and panic; post PR, participants reported reduced fear and felt able to increase
      their activities. These findings add to our understanding of the impact of PR on
      individuals' experience of activity and may contribute to improved programmes by
      addressing patients' needs.

PMID- 19603126
TI  - Laser excision of encrusted intra-vesical tension-free vaginal tape (TVT).
AB  - The widely used minimally invasive tension-free vaginal tape for stress urinary
      incontinence has been associated with the complication of intra-vesical tape
      erosion and unrecognised intra-operative bladder perforation. Although rare, it
      represents a surgical challenge due to its proximity to the bladder mucosa and
      also encrustation of the tape. We describe a minimally invasive technique for the
      effective removal of the encrusted tape.

PMID- 19603128
TI  - Hill coefficient analysis of transmembrane helix dimerization.
AB  - Here, we employed the Hill equation, used broadly to characterize cooperativity
      in protein-ligand binding, to describe the dimerization of transmembrane (TM)
      helices in hydrophobic environments. The Hill analysis of wild-type fibroblast
      growth factor receptor 3 (FGFR3) TM domain dimerization gives a Hill coefficient
      of approximately 1 for lipid bilayers but only approximately 0.2 for sodium
      dodecyl sulfate (SDS) micelles. We propose that this finding is indicative of
      heterogeneity in FGFR3 TM dimer structure and stability in SDS micelles. We
      further speculate that (1) the Hill equation can be used as a tool to assess the
      existence of multiple structural states of TM dimers in different hydrophobic
      environments and (2) the structural heterogeneity, detectable by Hill analysis,
      may be the underlying reason for the broad peaks and the low resolution NMR
      studies of peptides in detergents.

PMID- 19603129
TI  - pH Effect of the sphingomyelin membrane interfacial tension.
AB  - The effect of pH on the interfacial tension of a sphingomyelin membrane in
      aqueous solution has been studied. Three models describing H(+) and OH(-) ion
      adsorption on the bilayer lipid surface are presented. In models I and II, the
      membrane surface is continuous, with uniformly distributed functional groups as
      centers of H(+) and OH(-) ion adsorption. In model III, the membrane surface is
      composed of lipid molecules, with and without adsorbed H(+) and OH(-) ions. The
      contribution of each individual lipid molecule to the overall interfacial tension
      of the bilayer was assumed to be additive in models I and II. In model III, the
      Gibbs isotherm was used to describe adsorption of H(+) and OH(-) ions at the
      bilayer surface. Theoretical equations are derived to describe the interfacial
      tension as a function of pH for all three models. Maximum interfacial tension was
      observed experimentally at the isoelectric point.

PMID- 19603127
TI  - Prevalence and risk factors for bothersome lower urinary tract symptoms in women
      with diabetes mellitus from hospital-based diabetes clinic.
AB  - INTRODUCTION AND HYPOTHESIS: There is limited data on prevalence and risk factors
      for bothersome lower urinary tract symptoms (LUTS) in women with diabetes
      mellitus (DM). This study assesses prevalence and risk factors for bothersome
      LUTS and voiding dysfunction in women with DM. METHODS: Two hundred twenty women
      participated in this study. Participants completed the King's health
      questionnaire and the international consultation on incontinence-female lower
      urinary tract symptom questionnaire. Symptoms prevalence and urinary flow rate
      were assessed. Logistic regression models for risk factors of bothersome LUTS and
      voiding dysfunction were constructed. RESULTS: One hundred forty-eight women
      completed the study. Sixty-one women (41%) had bothersome LUTS. Urgency
      incontinence, urgency, and nocturia were the most bothersome. Fifty-six (38%) had
      voiding dysfunction. Neuropathy and glycosylated haemoglobin were independent
      risk factors for voiding dysfunction. Voiding dysfunction did not affect quality
      of life in women with DM. CONCLUSIONS: Overactive bladder symptoms are the most
      bothersome in diabetic women. Neuropathy and glycosylated haemoglobin are risk
      factors for voiding dysfunction.

PMID- 19603130
TI  - Assessment of heavy metal and pesticide levels in soil and plant products from
      agricultural area of Belgrade, Serbia.
AB  - This study was aimed to assess the levels of selected heavy metals and pesticides
      in soil and plant products from an agricultural area of Belgrade, Serbia and to
      indicate possible sources and risks of contamination. Soil, vegetable, and fruit
      samples from the most important agricultural city areas were collected from July
      to November of 2006. Metal contents were determined by atomic absorption
      spectrometry, whereas pesticide residues were analyzed by gas chromatography-mass
      spectrometry after extraction performed using solid-phase microextraction
      technique. Soil characterization based on the determination of selected physical
      and chemical properties revealed heterogeneous soils belonging to different soil
      groups. The concentrations of lead, cadmium, copper, and zinc in soil samples do
      not exceed the limits established by national and international regulations.
      Residues of the herbicide atrazine were detected in three soil samples, with
      levels lower than the relevant limit. The presence of other herbicides, namely
      prometryn, chloridazon, acetochlor, flurochloridone, and napropamide, was
      registered in some soil samples as well. Among the insecticides investigated in
      the soil, fenitrothion and chlorpyrifos were the only ones detected. In most of
      the investigated vegetable samples from the Obrenovac area, Pb and Cd contents
      are higher in comparison with the maximum levels, indicating the emission of coal
      combustion products from local thermal power plants as a possible source of
      contamination. Residue levels of some herbicides and insecticides (metribuzin,
      trifluralin, pendimethalin, bifenthrin, chlorpyrifos, and cypermethrin)
      determined in tomato, pepper, potato, and onion samples from Slanci, Ovca, and
      Obrenovac areas are even several times higher than the maximum residue levels.
      Inappropriate use of these plant protection products is considered to be the most
      probable reason of contamination. Because increased levels of heavy metals and
      pesticide residues found in plant products could pose a risk to consumers'
      health, their continual monitoring before product distribution to city markets is
      indispensable.

PMID- 19603131
TI  - Risk assessment of residual DDTs in freshwater and marine fish cultivated around
      the Pearl River Delta, China.
AB  - Six species of freshwater fish collected from 10 fishponds in Shunde and
      Zhongshan, China, four species of marine fishes collected from different
      mariculture farms [four in Hong Kong (Tung Lung Chau, Ma Wan, Cheung Chau and Kat
      O) and two in mainland China (Daya Bay and Shenzhen)] together with feed (both
      trash fish and commercial pellets) and sediment were analyzed for DDTs. Total
      DDTs in freshwater fish flesh decreased in the order of: carnivores [1742
      microg/kg lipid weight (l.w.)] > herbivores (165 microg/kg, l.w.) > omnivores
      (42.5 microg/kg, l.w.), with the highest concentration detected in mandarin fish
      (Siniperca chuatsi) (2641 microg/kg, l.w.). For marine fish, snubnose pompano
      (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides) collected
      in Ma Wan contained elevated levels of total DDTs (2590 and 2034 microg/kg l.w.,
      respectively). Trash fish used in both freshwater and marine fish farms contained
      significantly higher levels (86.5-641 microg/kg l.w.) (p < 0.05) of DDTs than in
      commercial pellets, but correlations between DDT levels in fish feed and muscle
      were not significant. The elevated biota-sediment accumulating factor for tilapia
      (Tilapia mossambicus) (24.1) indicated that accumulation of DDTs from sediment to
      the fish was evident. It can be concluded that trash fish should not be used for
      fish culture in order to lower the level of residual DDTs in fish muscle.

PMID- 19603132
TI  - Carotid and vertebrobasilar rete mirabile: a case report.
AB  - Bilateral symmetrical absence of the cavernous segments of the internal carotid
      artery (ICA) and absence of proximal basilar artery with a compensating arterial
      network (rete mirabile) is quite rare. Although it is found in some lower mammals
      as a physiological network supplying the circle of Willis, it is associated with
      ICA hypoplasia or nonpersistence in humans. We present a case of both cavernous
      ICA and proximal part of basilar artery absence associated with rete formation,
      which was an incidental finding during cerebral angiography in a 32-year-old
      woman with a complaint of left maxillary sinus mass.

PMID- 19603133
TI  - Renal dysfunction is associated with shorter telomere length in heart failure.
AB  - BACKGROUND: Renal dysfunction is a frequent comorbidity associated with high
      mortality in patients with chronic heart failure (CHF). The intrinsic biological
      age might affect the ability of the kidney to cope with the challenging
      environment caused by CHF. We explored the association between leukocyte telomere
      length, a marker for biological age, and renal function in patients with CHF.
      METHODS AND RESULTS: Telomere length was determined by a real-time quantitative
      polymerase chain reaction in 866 CHF patients. Renal function was estimated with
      the simplified Modification of Diet in Renal Disease equation. The median age was
      74 (interquartile range 64-79) years, 61% male, left ventricular ejection
      fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40
      68) ml/min/1.73 m(2). Telomere length was associated with renal function
      (correlation coefficient 0.123, P < 0.001). This relationship remained
      significant after adjustment for age, gender, age of CHF onset (standardized-beta
      0.091, P = 0.007). Also additionally adjusting for the severity of CHF and
      baseline differences did not change our findings. CONCLUSION: The association
      between shorter leukocyte telomere length and reduced renal function in heart
      failure suggests that intrinsic biological aging affects the ability of the
      kidney to cope with the systemic changes evoked by heart failure.

PMID- 19603134
TI  - Rendezvous gastrotomy technique using direct percutaneous endoscopic gastrostomy
      for transgastric cholecystectomy in hybrid natural orifice translumenal
      endoscopic surgery.
AB  - BACKGROUND/PURPOSE: Transgastric access is a major route in natural orifice
      translumenal endoscopic surgery (NOTES); gastrotomy should be performed unless it
      would damage surrounding organs in the peritoneal cavity. This article describes
      a novel rendezvous gastrotomy technique over a direct percutaneous endoscopic
      gastrostomy (PEG). METHODS: In six live porcines, the gastrotomy involved
      applying a direct PEG through the abdominal wall into the stomach and exchanging
      to a needle trocar. An endoscopic balloon catheter was passed through the trocar
      by rendezvous technique. Then the inflated balloon and endoscope were advanced to
      the peritoneal cavity through the gastrotomy. Transgastric cholecystectomy was
      performed with a hybrid needle grasper through the same percutaneous site and the
      gastrotomy was closed with endoscopic clips. RESULTS: The rendezvous gastrotomy
      technique could reduce guidewire exchange. The success rate was 100% (6/6). Mean
      times for transgastric peritoneoscopy and cholecystectomy were 25.5 and 83.5 min.
      Mortality and morbidity was 0%. The addition of the extra trocar was unnecessary
      in all procedures. DISCUSSIONS/CONCLUSIONS: The advantage of this introduction
      system includes the creation of controlled gastric perforation, which is easier
      to close. It provides reliable transgastric access and increases safety. It
      simplifies transgastric NOTES and provides less invasive hybrid NOTES procedure.

PMID- 19603135
TI  - Coping strategy when patients with quiescent Crohn's disease recognize that their
      conditions are worsening.
AB  - BACKGROUND: Although self-management is important for Crohn's disease (CD), there
      is no research focusing on self-management, especially in worsening conditions.
      The purpose of this study was to investigate how quiescent CD patients cope with
      their conditions worsening. METHODS: A questionnaire containing six types of
      coping strategy for worsening conditions was created based on a semi-structured
      interview. Seventy-six quiescent CD patients participated in this study. We also
      analyzed the related factors of each coping strategy for worsening conditions.
      RESULTS: The total percentage of subjects who adopt the strategy of "change
      contents of meals" 'always' or 'often' was approximately 70%. On the other hand,
      the strategy of "see a doctor immediately" was approximately 20% in total of
      'always' or 'often'. When 'sometimes' was added, "take extra medicine" was
      approximately 42%. The subjects with experience of hospitalization within 3 years
      (Z = -2.352, P = 0.019), presence of supplemental elemental diet (Z = -5.182, P <
      0.001), or 1 year or less interval since last relapse (Z = -3.352, P = 0.001)
      showed a significant tendency to adopt the coping strategy of "take (add to)
      elemental diet." CONCLUSION: The major coping strategy was "change contents of
      meals," and the minor coping strategy was "see a doctor immediately." The
      subjects with unstable disease state adopted the coping strategy of "take (add
      to) elemental diet." The coping strategies for worsening conditions vary
      according to patients' backgrounds. The coping type should be taken into account
      when treating CD patients.

PMID- 19603136
TI  - Review of current microsurgical management of insular gliomas.
AB  - The insular lobe is a functionally complex structure, harbouring peculiar
      anatomical and vascular features and specific neuronal connectivity with
      surrounding cerebral structures. It is situated in the depth of the Sylvian
      fissure and can be affected by either low-grade or high-grade gliomas. Because of
      its complexity, surgery of insular tumours has been traditionally regarded as
      hazardous. Nonetheless, currently improved diagnostic, neurophysiological and
      surgical tools allow the neurosurgeon to perform surgery of insular gliomas in a
      safer way, thus bringing forward the pioneering work performed by neurosurgeons
      in the past two decades.The aim of this paper is to provide the reader with an
      updated review of the anatomy, the clinical picture, diagnosis and surgical
      management of insular gliomas.

PMID- 19603137
TI  - Neuropathic pain after stapled hemorrhoidopexy.

PMID- 19603138
TI  - Successful pregnancy and delivery following a Malone antegrade continence enema
      procedure.
AB  - Malone antegrade continence enema (MACE) procedures are an effective treatment
      for both intractable faecal incontinence and constipation of neurogenic aetiology
      and have traditionally been used in a paediatric setting. MACE procedures are now
      being performed more commonly in adults suffering idiopathic chronic constipation
      where they are also effective. Increasing use in otherwise healthy adult females
      raises concerns about the durability of the appendiceal conduit should the
      patient become pregnant. We report the first case of successful pregnancy after a
      MACE procedure with an umbilical stoma and discuss the impact of the pregnancy on
      MACE function.

PMID- 19603139
TI  - Chronic pelvic abscedation after completion proctectomy in an irradiated pelvis:
      another indication for ENDO-sponge treatment?
AB  - Six years after completion proctectomy, a patient presented with invalidating
      pain, fever and massive mucopurulent secretion through the perineal wound after
      completion proctectomy. CT-scan revealed a large presacral abscess and
      osteonecrosis of the sacrum. The patient consented to placement of an ENDO-sponge
      (B. Braun Medical B.V., Melsungen Germany). On day 4 granulation tissue covered
      the walls of the cavity and the amount of necrotic tissue and fibrin was reduced.
      The foam was changed every 4 days and treatment was continued for 20 days. On day
      20, vacuum assisted closure therapy was stopped and the remnant cavity was
      further rinsed with saline. There was no more evacuation of mucus or pus. Three
      months later, the patient was symptom free and only a small perineal dimple
      remained. ENDO-sponge (B. Braun Medical B.V., Melsungen Germany) treatment is
      possible for presacral abscedation which is a well-known complication following
      abdominoperineal rectum amputation.

PMID- 19603140
TI  - Evaluation by three-dimensional anal endosonography of injectable silicone
      biomaterial (PTQ) implants to treat fecal incontinence: long-term localization
      and relation with the deterioration of the continence.
AB  - BACKGROUND: The purposes of the study were the long-term evaluation of silicone
      implants with three-dimensional (3D) anal endosonography and its correlation with
      anal incontinence. METHODS: Fifteen patients were injected with silicone because
      of anal incontinence and co-existing internal anal sphincter disruption (n = 8)
      or thinning (n = 7). The evaluation was performed with the Wexner score and 3D
      anal endosonographies. RESULTS: Forty-four implants were performed. The
      endosonography at 3 months detected that all the implants were properly located.
      At 24 months, it detected 37/44 implants of initially injected and 33/37 were
      properly located. Four of 37 implants had moved and 7/44 were neither in the anus
      nor in the rectum. A total of 8/15 patients had their implants correctly placed.
      Globally, silicone implants significantly improved fecal continence. CONCLUSIONS:
      The silicone implants might have moved or even be lost. The continence
      deterioration suffered by most patients after the first year of the injection has
      no relation with the localization and number of implants that the patients have.

PMID- 19603141
TI  - Reverse signaling using an inducible costimulator to enhance immunogenic function
      of dendritic cells.
AB  - A costimulatory signal from an inducible costimulator (ICOS) of T cells plays a
      critical role in immunological homeostasis. This study shows that the interaction
      of ICOSIg and its ligand (ICOSL) on mouse bone marrow-derived dendritic cells
      (DCs) induces a p38-MAPK dependent elevation of interleukin 6 (IL-6). It also
      enhances phagocytosis and the antigen-presentation function of DCs in vitro,
      further favoring cell-mediated immunity in vivo. As seen for other types of
      costimulator molecules expressed in the T cells in the CD28 family, it is shown
      here for the first time that ICOS can also deliver reverse signals through its
      ligand to ICOSL-expressing cells. These reverse signals in turn transfer positive
      immunogenic information to bone marrow-derived DCs. Our work therefore provides
      new recognition of an ICOSL/ICOS signal pathway in immunity and also supplies
      more evidence that this ICOSL/ICOS signal pathway is a reasonable target for
      therapeutic drugs.

PMID- 19603142
TI  - Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma
      spheroids by activating ADAM10.
AB  - Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We
      analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three
      dimensional cultures. By using GFP expression and immunohistochemistry, we show
      that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer
      spheroids to become disorganized which was accompanied by a disruption of cell
      cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but
      not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In
      addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of
      ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin,
      prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data
      suggest that hMSCs interfere with cell-cell adhesion and enhance migration of
      breast cancer cells by activating ADAM10.

PMID- 19603144
TI  - Dwarf 88, a novel putative esterase gene affecting architecture of rice plant.
AB  - Rice architecture is an important agronomic trait that affects grain yield. We
      characterized a tillering dwarf mutant d88 derived from Oryza sativa ssp.
      japonica cultivar Lansheng treated with EMS. The mutant had excessive shorter
      tillers and smaller panicles and seeds compared to the wild-type. A reduction in
      number and size of parenchyma cells around stem marrow cavity as well as a delay
      in the elongation of parenchyma cells caused slender tillers and dwarfism in the
      d88 mutant. The D88 gene was isolated via map-based cloning and identified to
      encode a putative esterase. The gene was expressed in most rice organs, with
      especially high levels in the vascular tissues. The mutant carried a nucleotide
      substitution in the first exon of the gene that led to the substitution of
      arginine for glycine, which presumably disrupted the functionally conserved N
      myristoylation domain of the protein. The function of the gene was confirmed by
      complementation test and antisense analysis. D88, thus, represents a new category
      of genes that regulates cell growth and organ development and consequently plant
      architecture. The potential relationship between the tiller formation associated
      genes and D88 is discussed and future identification of the substrate for D88 may
      lead to the characterization of new pathways regulating plant development.

PMID- 19603146
TI  - Genotypes of Brassica rapa respond differently to plant-induced variation in air
      CO2 concentration in growth chambers with standard and enhanced venting.
AB  - Growth chambers allow measurement of phenotypic differences among genotypes under
      controlled environment conditions. However, unintended variation in growth
      chamber air CO2 concentration ([CO2]) may affect the expression of diverse
      phenotypic traits, and genotypes may differ in their response to variation in
      [CO2]. We monitored [CO2] and quantified phenotypic responses of 22 Brassica rapa
      genotypes in growth chambers with either standard or enhanced venting. [CO2] in
      chambers with standard venting dropped to 280 micromol mol(-1) during the period
      of maximum canopy development, approximately 80 micromol mol(-1) lower than in
      chambers with enhanced venting. The stable carbon isotope ratio of CO2 in chamber
      air (delta13C(air)) was negatively correlated with [CO2], suggesting that
      photosynthesis caused observed [CO2] decreases. Significant genotype x chamber
      venting interactions were detected for 12 of 20 traits, likely due to differences
      in the extent to which [CO2] changed in relation to genotypes' phenology or
      differential sensitivity of genotypes to low [CO2]. One trait, 13C discrimination
      (delta13C), was particularly influenced by unaccounted-for fluctuations in
      delta13C(air) and [CO2]. Observed responses to [CO2] suggest that genetic
      variance components estimated in poorly vented growth chambers may be influenced
      by the expression of genes involved in CO2 stress responses; genotypic values
      estimated in these chambers may likewise be misleading such that some mapped
      quantitative trait loci may regulate responses to CO2 stress rather than a
      response to the environmental factor of interest. These results underscore the
      importance of monitoring, and where possible, controlling [CO2].

PMID- 19603143
TI  - An in vitro study, evaluating the effect of sunitinib and/or lapatinib on two
      glioma cell lines.
AB  - AIM: We sought to assess the effect of sunitinib and lapatinib applied either
      alone or in combination, on U87 and M059K glioma cells. METHODS: Both cell lines
      were cultured as recommended by the manufacturer. Sunitinib and lapatinib were
      applied, either separately or in combination, in the cultured cells after cell
      attachment at doses of 10 nM, 100 nM, 1 microM and 10 microM. To determine
      whether the agents affect the proliferation of glioma cells, the 3-[4,5
      dimethylthiazol-2-yl]-2,5 dimethyltetrazolium bromide assay was used. Apoptosis
      was detected using annexin V/propidium iodide detection assay, migration assay
      was performed in 24-well microchemotaxis chambers. The release of MMPs into the
      culture medium of U87 and M059K cells was measured by zymography. RESULTS: Both
      agents, administered either alone or in combination, decreased cell proliferation
      in a dose-dependent manner 48 h after their application in both cell lines. The
      inhibition of their combination was statistically different than the inhibition
      of each agent alone. Apoptosis was increased and migration of U87 and M059K cells
      was inhibited either by each agent alone or their combination. MMPs levels
      remained unaffected by the application of both agents in U87 cells. However, MMP
      9 and MMP-2 levels were decreased 48 h after treatment of M059K cells with
      sunitinib either alone or in combination with lapatinib. CONCLUSION: Sunitinib
      and/or lapatinib appear to exhibit significant effects on proliferation,
      apoptosis and migration of glioma cells. When applied alone, sunitinib appears to
      be a more potent inhibitor than lapatinib.

PMID- 19603145
TI  - [Airway management in the German air rescue service].
AB  - BACKGROUND: The equipment carried in rescue helicopters concerning airway
      management is not standardized in Germany. The current DIN/EN equipment
      regulations are not detailed for every single item resulting in differences
      between the various rescue bases. The aim of this survey was to show existing
      differences in airway management equipment. METHODS: All 72 German air rescue
      helicopters listed in the ADAC air rescue stations atlas 2006/2007 received a
      questionnaire. RESULTS: A total of 64 bases returned the questionnaire (88.9%).
      The most frequent types of supraglottic airway equipment were laryngeal masks
      (67.2%), Combitubes (32.8%) and laryngeal tubes (29.7%). Cricothyrotomy sets were
      more frequent (68.8%) than tracheostomy sets (35.9%). Of the bases 18.8% had
      masks suitable for non-invasive ventilation (NIV). All helicopters were equipped
      to carry out capnometry. CONCLUSIONS: The rescue helicopters were found to have
      differences with respect to the equipment carried for airway management. Medical
      treatment according to current guidelines is possible on almost all bases.

PMID- 19603147
TI  - Pregnancy and systemic lupus erythematosus: review of clinical features and
      outcome of 51 pregnancies at a single institution.
AB  - Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the
      coexistence of pregnancy is by no means a rare event. How SLE and its treatment
      affects pregnancy outcome is still a matter of debate. Assessment of the
      reciprocal clinical impact of SLE and pregnancy was investigated in a cohort
      study. We reviewed the clinical features, treatment, and outcomes of 43 pregnant
      SLE patients with 51 pregnancies followed from 1993 to 2007 at a tertiary
      university hospital. The age of patients was 28.7 +/- 5.4 years and SLE was
      diagnosed at age of 23.0 +/- 6.1 years. Previous manifestations of SLE included
      lupus nephritis (14 patients) and secondary antiphospholipid syndrome (11
      patients). Thirty-five pregnant patients (69%) were in remission for more than 6
      months at the onset of pregnancy. Patients were being treated with low doses of
      prednisone (29), hydroxychloroquine (20), azathioprine (five), acetylsalicylic
      acid (51), and low molecular weight heparin (13). Sixteen pregnancy-associated
      flares were documented, mainly during the second trimester (42%) and also in the
      following year after delivery (25%). Renal involvement was found in 11 cases
      (68%). Spontaneous abortion occurred in 6%, 16% had premature deliveries, and 74%
      were delivered at term. No cases of maternal mortality occurred. No cases of
      fetal malformation were recorded. There was one intrauterine fetal death and one
      neonatal death at 24 gestational weeks. Pregnant women with SLE are high risk
      patients, but we had a 90% success rate in our cohort. A control disease activity
      strategy to target clinical remission is essential.

PMID- 19603148
TI  - Sarcoidosis presenting as "corset-like" myelopathy: a description of six cases
      and literature review.
AB  - Sarcoidosis of the spinal cord is rare, even more so as the initial presentation
      of the disease. We describe six cases of spinal cord sarcoidosis and delineate a
      distinguishing feature which may allow for a timely diagnosis. All patients were
      admitted with complaints of a "corset-like" pressure in the lower chest and later
      developed cranial nerve palsies (two patients), parasthesias/paraparesis (two
      patients), fever of unknown origin (one patient), and bilateral proptosis (one
      patient). Serological tests, immunological screening, cerebrospinal fluid (CSF)
      analysis, bacteriological and viral testing were performed in all patients.
      Spinal and cerebral MRI, high-resolution computed tomography (HRCT) of the chest
      and gallium scan suggested the diagnosis of neurosarcoidosis of the spine while a
      biopsy of mediastinal lymph nodes, extra-ocular muscles, or spinal cord confirmed
      it. CSF showed inflammatory signs in 66% of patients and serum ACE levels were
      increased in a similar fraction. MRI revealed a gadolinium-enhanced thickening of
      the cord at the thoracic level in three patients whereas three other patients had
      normal spinal MRI despite similar symptoms. The presence of mediastinal
      lymphadenopathy on HRCT of the chest suggested the diagnosis in a third of
      patients. Patients were treated with steroid, immunosuppressive therapy and/or
      biologic therapies, with complete resolution in one case, improvement in four,
      and a somewhat deteriorating course, with development of spinal cord atrophy in
      the final case. As spinal cord involvement of sarcoidosis is extremely rare,
      making the diagnosis in the absence of systemic disease is challenging. The cases
      herein described suggest that sensory disturbance in a "corset-like" distribution
      may be indicative of neurosarcoidosis, especially when accompanied by extra-axial
      involvement such as cranial nerve palsies. This should prompt an evaluation for
      systemic involvement, keeping in mind that serum ACE and chest radiographs may be
      normal in the presence of primarily CNS-limited disease.

PMID- 19603149
TI  - Use of insulin glargine and cancer incidence in Scotland: a study from the
      Scottish Diabetes Research Network Epidemiology Group.
AB  - AIMS/HYPOTHESIS: The aim of the present study was to examine whether patients
      with diabetes in Scotland using insulin glargine have a greater cancer risk than
      patients using other types of insulin. METHODS: We used a nationwide diabetes
      clinical database that covers the majority of the Scottish population with
      diagnosed diabetes, and examined patients with diabetes who were exposed to any
      insulin therapy between 1 January 2002 and 31 December 2005. Among these we
      defined a fixed cohort based on exposure during a 4 month period in 2003 (n =
      36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users
      across the period (n = 12,852 in whom 381 cancers occurred). Records from these
      cohorts were linked to cancer registry data up to the end of 2005. We used Cox
      proportional hazards models for survival analyses. RESULTS: Those receiving any
      insulin glargine (n = 3,959) had the same incidence rate for all cancers as those
      not receiving insulin glargine (HR 1.02, 95% CI 0.77-1.36, p = 0.9 in the fixed
      cohort) The subset of patients using insulin glargine alone (n = 447) had a
      significantly higher incidence of all cancers than those using other insulins
      only (n = 32,295) (HR 1.55, 95% CI 1.01-2.37, p = 0.045), and those using insulin
      glargine with other insulins (n = 3,512) had a slightly lower incidence (HR 0.81,
      95% CI 0.55-1.18, p = 0.26). There were important differences in baseline
      characteristics between these three groups, although the risk ratios were broadly
      unaltered on adjustment for these. Overall, there was no increase in breast
      cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79-2.83,
      though insulin glargine only users had a higher rate than those using non
      glargine insulin only (HR 3.39, 95% CI 1.46-7.85, p = 0.004). Among type 2
      diabetic incident insulin users, no significant difference between the three
      groups was observed with respect to all cancer or breast cancer. All the above
      HRs are adjusted for age, calendar time prior cancer and type of diabetes, as
      appropriate, and are stratified according to sex. CONCLUSIONS/INTERPRETATION:
      Overall, insulin glargine use was not associated with an increased risk of all
      cancers or site-specific cancers in Scotland over a 4 year time frame. Given the
      overall data, we consider the excess of cases of all cancers and breast cancer in
      the subgroup of insulin glargine only users to more likely reflect allocation
      bias rather than an effect of insulin glargine itself.

PMID- 19603150
TI  - Differences in trends in estimated incidence of myocardial infarction in non
      diabetic and diabetic people: Monitoring Trends and Determinants on
      Cardiovascular Diseases (MONICA)/Cooperative Health Research in the Region of
      Augsburg (KORA) registry.
AB  - AIMS/HYPOTHESIS: One major objective of the St Vincent Declaration was to reduce
      the excess risk of myocardial infarction in patients with diabetes mellitus. We
      estimated the trend of the incidence and relative risk of myocardial infarction
      in the diabetic and non-diabetic populations in southern Germany from 1985 to
      2006. METHODS: Using data from the Monitoring Trends and Determinants on
      Cardiovascular Diseases (MONICA)/Cooperative Health Research in the Region of
      Augsburg (KORA) Project in southern Germany, we ascertained all fatal and non
      fatal first myocardial infarctions between 1985 and 2006 (n = 14,891, age 25-74
      years). We estimated the diabetic and the non-diabetic populations using data on
      diabetes prevalence from surveys, and evaluated incidence of myocardial
      infarction in the two estimated populations. To test for time trends, we fitted
      Poisson regression models. RESULTS: Of individuals with first myocardial
      infarction, 71% were male and 28% known to have diabetes. In the non-diabetic
      population, myocardial infarction incidence decreased by about 1.5% to 2.0% per
      year. A comparable decrease was seen in the population of diabetic women.
      However, in the population of diabetic men, incidence of myocardial infarction
      increased by about 1% per year. Over the whole study period, myocardial
      infarction incidence decreased by 34% and 27% in non-diabetic men and women
      respectively (RR 0.66, 95% CI 0.59-0.74 and 0.73, 0.62-0.87 respectively). In
      diabetic women, it decreased by 27% (RR 0.73, 0.61-0.88), whereas in diabetic
      men, it increased by 25% (RR 1.25, 1.07-1.45). CONCLUSIONS/INTERPRETATION: Our
      results suggest that the St Vincent goal of reducing excess cardiovascular
      morbidity in diabetic individuals has not been achieved and that the situation in
      men has actually got worse.

PMID- 19603151
TI  - The analysis of core and symbiotic genes of rhizobia nodulating Vicia from
      different continents reveals their common phylogenetic origin and suggests the
      distribution of Rhizobium leguminosarum strains together with Vicia seeds.
AB  - In this work, we analysed the core and symbiotic genes of rhizobial strains
      isolated from Vicia sativa in three soils from the Northwest of Spain, and
      compared them with other Vicia endosymbionts isolated in other geographical
      locations. The analysis of rrs, recA and atpD genes and 16S-23S rRNA intergenic
      spacer showed that the Spanish strains nodulating V. sativa are phylogenetically
      close to those isolated from V. sativa and V. faba in different European,
      American and Asian countries forming a group related to Rhizobium leguminosarum.
      The analysis of the nodC gene of strains nodulating V. sativa and V. faba in
      different continents showed they belong to a phylogenetically compact group
      indicating that these legumes are restrictive hosts. The results of the nodC gene
      analysis allow the delineation of the biovar viciae showing a common phylogenetic
      origin of V. sativa and V. faba endosymbionts in several continents. Since these
      two legume species are indigenous from Europe, our results suggest a world
      distribution of strains from R. leguminosarum together with the V. sativa and V.
      faba seeds and a close coevolution among chromosome, symbiotic genes and legume
      host in this Rhizobium-Vicia symbiosis.

PMID- 19603152
TI  - Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal
      cell proliferation and survival in adult rodent hippocampus.
AB  - RATIONALE: Currently available antidepressants upregulate hippocampal
      neurogenesis and prefrontal gliogenesis after chronic administration, which could
      block or reverse the effects of stress. Allosteric alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid receptor potentiators (ARPs), which have novel targets
      compared to current antidepressants, have been shown to have antidepressant
      properties in neurogenic and behavioral models. OBJECTIVES: This study analyzed
      the effect of the ARP Org 26576 on the proliferation, survival, and
      differentiation of neurons and glia in the hippocampus and prelimbic cortex of
      adult rats. MATERIALS AND METHODS: Male Sprague-Dawley rats received acute
      (single day) or chronic (21 day) twice-daily intraperitoneal injections of Org
      26576 (1-10 mg/kg). Bromodeoxyuridine (BrdU) immunohistochemistry was conducted
      24 h or 28 days after the last drug injection for the analysis of cell
      proliferation or survival, respectively. Confocal immunofluorescence analysis was
      used to determine the phenotype of surviving cells. RESULTS: Acute administration
      of Org 26576 did not increase neuronal cell proliferation. However, chronic
      administration of Org 26576 increased progenitor cell proliferation in dentate
      gyrus (approximately 40%) and in prelimbic cortex (approximately 35%) at the 10
      mg/kg dosage. Cells born in response to chronic Org 26576 in dentate gyrus
      exhibited increased rates of survival (approximately 30%) with the majority of
      surviving cells expressing a neuronal phenotype. CONCLUSION: Findings suggest
      that Org 26576 may have antidepressant properties, which may be attributed, in
      part, to upregulation of hippocampal neurogenesis and prelimbic cell
      proliferation.

PMID- 19603153
TI  - Enhanced excitability of the corticospinal pathway of the ankle extensor and
      flexor muscles during standing in humans.
AB  - The purpose of this study was to investigate how the recruitment properties of
      the corticospinal pathway are modulated in the soleus (SOL) and tibialis anterior
      (TA) muscles depending on postures. A wide range of stimulus intensities were
      applied via transcranial magnetic stimulation over the primary motor cortex
      during standing (STD) and sitting (SIT) with a comparable background activity
      level in each muscle. The relationship between the stimulation intensities and
      the size of motor-evoked potentials was assessed by the Boltzmann sigmoid
      function, which is characterized by a plateau value, maximum slope, and
      threshold. The plateau value and maximum slope were significantly higher during
      STD than during SIT in the SOL muscle (STD vs. SIT, plateau value: 50.0 +/- 21.8
      vs. 33.9 +/- 12.3 mV ms, maximal slope: 1.6 +/- 0.7 vs. 1.2 +/- 0.5 mV ms/%
      maximal stimulator output). Similar changes of the parameters were also observed
      in the TA muscle (STD vs. SIT, plateau value: 71.0 +/- 22.9 vs. 41.4 +/- 16.1 mV
      ms, maximal slope: 5.0 +/- 2.0 vs. 2.5 +/- 0.7 mV ms/% maximal stimulator
      output). The threshold did not differ significantly between the two conditions
      and both muscles. These results indicate that the central nervous system requires
      a different control for each postural condition; that is, the relative balance of
      the excitatory and inhibitory inputs to the corticospinal pathways as well as the
      number of neurons of subliminal fringe in the corticospinal pathway was increased
      during STD compared with those during SIT.

PMID- 19603154
TI  - Seretide withdrawal increases airway inflammation in moderate COPD patients.

PMID- 19603155
TI  - Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing
      white matter in children and young adults with tuberous sclerosis complex.
AB  - INTRODUCTION: Patients with tuberous sclerosis complex (TSC) frequently present
      with neurocognitive deficits which may be related to impaired white matter
      maturation. The purposes of our study were (a) to evaluate the white matter
      maturation in children and young adults with TSC by comparing the apparent
      diffusion coefficient (ADC) values of normal-appearing white matter (NAWM) with
      age-matched healthy controls and (b) to determine the association of NAWM-ADC
      values with the severity of neurological symptoms in TSC patients. METHODS:
      Twenty-three TSC patients who underwent magnetic resonance imaging/diffusion
      weighted imaging between January 2000 and January 2009 were studied. ADC values
      of NAWM were measured in the frontal, parietal, occipital lobes, and in the pons.
      ADC data were compared with age-matched normative data derived from healthy
      controls. Patients were neurologically scored by a pediatric neurologist. Two
      sample t tests and linear regression were conducted using STATA software.
      RESULTS: ADC values of NAWM were higher in TSC patients compared with healthy
      controls; the increase, however, only reached statistical significance in the
      frontal white matter and pons in the age group between 96 and 144 months and in
      the right parietal and occipital white matter in the age group above 144 months.
      There was no significant change in neurological severity score per unit increase
      in ADC measurement. CONCLUSION: ADC values of NAWM appear increased in TSC
      patients. The abnormal ADC values suggest that myelination may be
      delayed/impaired in TSC patients, which could explain global neurocognitive
      deficits. Larger prospective studies, including diffusion tensor imaging, are
      necessary to validate our results.

PMID- 19603156
TI  - Apparent diffusion coefficient vale of the brain in patients with Gaucher's
      disease type II and type III.
AB  - INTRODUCTION: The aim of this work is to assess the usefulness of apparent
      diffusion coefficient (ADC) value of the brain for diagnosis of patients with
      Gaucher's disease type II and type III. METHODS: Prospective study was conducted
      upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1
      years) with Gaucher's disease type II and III and for age-matched control group
      (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo
      planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm(2)
      was done for all patients and volunteers. The ADC value was calculated in ten
      regions of the brain parenchyma and correlated with genotyping. RESULTS: There
      was significantly lower ADC value of the cortical frontal (P = 0.003), cortical
      temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal
      tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P =
      0.02) between patients and volunteers. There was significant difference in the
      ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05,
      respectively) between patients with heterozygous and homozygous gene mutation.
      CONCLUSION: We concluded that ADC value is a new promising quantitative imaging
      parameter that can be used for the detection of brain abnormalities in patients
      with Gaucher's disease type II and type III and has a correlation with
      genotyping.

PMID- 19603158
TI  - Problem in analyzing cystine stones using FTIR spectroscopy.
AB  - Cystine stones are produced by an inherited disorder of the transport of amino
      acid cystine that results in excess of cystine in the urine (cystinuria). Cystine
      calculi in urinary tract present a significant problem in patients. We have
      recorded that cystine calculi are very uncommon in our region. Cystine crystals
      are unusually identified in the urinary deposits. The problem of recognizing
      cystine by FTIR as a component in mixture of stones is significant. The problem
      is compounded by the similarity of wavelengths of cystine with that of whewellite
      and uric acid. The objective of this paper is to elucidate the problems of
      identifying cystine in stone analysis and identifying a solution to get over this
      deficiency. Out of 1,300 urinary stones analysed by ordinary wet chemical methods
      and infrared spectroscopy, 30 stone samples, which were reported to have cystine
      peaks in significant numbers, were selected. These samples were powdered, mixed
      with potassium bromide, pelletized and taken up for FTIR analysis. The wavelength
      patterns were scrutinized by comparing with the peaks obtained by the reference
      standards of cystine. Spectra were also obtained from pure cystine. Comparison of
      spectra with those of whewellite and uric acid was performed. Then the samples
      were taken for Scanning electron microscopy with elemental distribution analysis
      X-ray (SEM-EDAX). The samples were made conductive by gold sputtering and were
      fed into JEOL JSM 35 C SEM machine. Morphology was recorded by taking
      photographs. Further elemental distribution analysis (EDAX) was carried out to
      identify the elemental composition. Of the 30 samples taken up for FTIR analysis,
      all showed spectra identifiable with the reference peaks for cystine. However,
      when these peaks were compared with those of whewellite and uric acid, all the
      stone samples showed duplication of peaks for whewellite and uric acid and
      whewellite. The pure cystine spectra showed identifiable peaks are in the range
      of 3026, 1618.28, 1485, 846.75 cm(-1), etc. (from the standard spectrum of pure
      cystine). All the analysis findings were correlated with EDAX findings. On doing
      EDAX, we could separately find out the components present in a mixture. Three
      stones contained elemental pattern to fit with those of cystine. Even though it
      is difficult to find out the presence of cystine molecule in FTIR, it is possible
      to recognize it through EDAX and will be possible to confirm the presence of
      cystine in mixed urinary stones.

PMID- 19603161
TI  - The use of bioluminescence stimulant on the immobilized strain, P. putida mt-2
      KG1206, with toluene analog inducers and environmental samples.
AB  - This study was conducted to investigate the applicability of the stimulant
      conditions for the bioluminescence activity of a recombinant strain of
      Pseudomonas putida, mt-2 KG1206, when immobilized using alginate polymer. The
      bioluminescence activity of the immobilized strain was generally approximately
      three to five times lower than the subcultured strain, and the activity was
      observed to slowly decrease. These facts may have been caused by several factors,
      such as the low biomass and the time required for diffusion into the entrapped
      biomass. Although different inducers produced different degrees of stimulation,
      immobilized bacteria modified with KNO(3) consistently produced more
      bioluminescence than those treated with sodium lactate, regardless of the inducer
      chemical tested. Cells treated with KNO(3) exhibited 2.8 times greater
      bioluminescence than that of the control activity. This condition also stimulated
      the bioluminescence activities of the immobilized bacteria exposed to
      contaminated groundwater samples. Based on these results, the immobilized KG1206
      presented in this research can be used as a portable assay for the purpose of
      preliminary on-site monitoring of specific inducer contaminants, with subsequent
      off-site instrumental analysis, suggesting the potential of this immobilized cell
      for preliminary application in a field-ready bioassay.

PMID- 19603160
TI  - Electromagnetic field (EMF) effects on channel activity of nanopore OmpF protein.
AB  - In this study, the effects of nonionizing electromagnetic fields (EMF; 925 MHz)
      on the OmpF porin channel have been characterized at the single-channel level.
      Channel activity was recorded in real time by the voltage clamp method. Our
      results showed an increase in the frequency of channel gating and voltage
      sensitivity. The effects of EMF lasted for several milliseconds after the field
      source was terminated. However, the conductance levels of channels did not change
      significantly. Thermal effects of EMF on single-channel properties are a possible
      cause, based on theoretical evaluation of results that were comparable to those
      seen in conventional experiments at different temperatures. We conclude that EMF
      affects both the dynamics and conformation of the channel, either directly by
      affecting critical amino acid side-chain arrangement, or indirectly, via the
      electrolyte or the lipid membrane.

PMID- 19603162
TI  - Nitrogen removal by co-occurring methane oxidation, denitrification, aerobic
      ammonium oxidation, and anammox.
AB  - The pathway for removing NO(3)(-) and NH(4)(+) from wastewater in the presence of
      both CH(4) and O(2) was clarified by studying microbial activity and community.
      Batch incubation tests were performed to characterize the microbial activity of
      the sludge, which was acclimatized in a bioreactor in which O(2) and CH(4) were
      supplied to treat wastewater containing NO(3)(-) and NH(4)(+) . The tests showed
      that the sludge removed significant amounts of NO(3)(-) and NH(4)(+) in the
      presence of CH(4) and O(2), and the presence of the activity of methane
      oxidation, denitrification, nitrification, and anammox in the sludge. It was
      estimated that the total inorganic nitrogen removal was attributed to
      denitrification associated with methane oxidation as 53.4%, microbial
      assimilation as 37.9%, and anammox as 8.7%. Nitrification also contributed to
      NH(4)(+) decrease as 34.5% and anammox as 6.4%. Anammox activity was
      unambiguously demonstrated by (29)N(2) production in anaerobic batch incubation
      with (15)N-labeled inorganic nitrogen compounds. The presence of methane
      oxidizing bacteria and candidate denitrifiers in the sludge was shown by
      denaturing gradient gel electrophoresis of 16S rRNA gene fragments. Clone library
      analysis of the PCR-amplified 16S rRNA gene fragment using specific primers for
      aerobic ammonium oxidizer and anammox revealed the presence of these bacteria.
      The results reveal that complex nitrogen-removal processes occur in the presence
      of CH(4) and O(2) by methanotroph, denitrifier, aerobic ammonium oxidizer, and
      anammox.

PMID- 19603163
TI  - First report of a solid variant of aneurysmal bone cyst in the os sacrum.
AB  - We report on a 19-year-old woman with a rapidly growing, solid variant of
      aneurysmal bone cyst (solid ABC) in the right part of the lateral mass of the
      sacrum. On admission, the magnetic resonance imaging (MRI) scan disclosed an
      inhomogeneous low intensity mass right of the centre of the os sacrum with a
      diameter of 38 x 64 mm and a height of 56 mm on T1 and T2 weighted images. The
      mass showed homogenous high signal intensity on Gd-enhanced images. Computed
      tomography demonstrated an expansile osteolytic lesion and (99m)Tc-methylene
      diphosphonate bone scintigraphy revealed uniform accumulation in the lesion. The
      histological evaluation showed a proliferation of fibroblasts, histiocytes,
      chronic inflammatory cells and numerous multinucleated giant cells. Nevertheless,
      the cells were devoid of nuclear atypia. A cystic component was not observed. In
      spite of thorough curettage, the patient suffered from recurrence and severe
      neurological deficits. A review of the literature revealed no previous cases of
      solid ABC in the sacrum.

PMID- 19603164
TI  - Imaging features of foot osteoid osteoma.
AB  - OBJECTIVES: We performed a retrospective review of the imaging of nine patients
      with a diagnosis of foot osteoid osteoma (OO). MATERIALS AND METHODS:
      Radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) had
      been performed in all patients. Radiographic features evaluated were the
      identification of a nidus and cortical thickening. CT features noted were nidus
      location (affected bone-intramedullary, intracortical, subarticular) and nidus
      calcification. MRI features noted were the presence of an identifiable nidus,
      presence and grade of bone oedema and whether a joint effusion was identified.
      RESULTS: Of the nine patients, three were female and six male, with a mean age of
      21 years (range 11-39 years). Classical symptoms of OO (night pain, relief with
      aspirin) were identified in five of eight (62.5%) cases (in one case, the medical
      records could not be retrieved). In five patients the lesion was located in the
      hindfoot (four calcaneus, one talus), while four were in the mid- or forefoot
      (two metatarsal and two phalangeal). Radiographs were normal in all patients with
      hindfoot OO. CT identified the nidus in all cases (89%) except one terminal
      phalanx lesion, while MRI demonstrated a nidus in six of nine cases (67%). The
      nidus was of predominantly intermediate signal intensity on T1-weighted (T1W)
      sequences, with intermediate to high signal intensity on T2-weighted (T2W)
      sequences. High-grade bone marrow oedema, limited to the affected bone and
      adjacent soft tissue oedema was identified in all cases. CONCLUSIONS: In a young
      patient with chronic hindfoot pain and a normal radiograph, MRI features
      suggestive of possible OO include extensive bone marrow oedema limited to one
      bone, with a possible nidus demonstrated in two-thirds of cases. The presence or
      absence of a nidus should be confirmed with high-resolution CT.

PMID- 19603165
TI  - Proximal femoral replacements for metastatic bone disease: financial implications
      for sarcoma units.
AB  - Metastatic pathological fractures of the proximal femur are increasingly treated
      by endoprosthetic proximal femoral replacement. We report the results and the
      costs incurred performing these procedures at our supra-regional sarcoma unit.
      Sixty-two patients underwent 63 proximal femoral replacements for metastatic bone
      disease over a seven-year period. Breast cancer was the most common primary
      pathology. One patient underwent a revision procedure for infection. Twenty-two
      patients suffered dislocations, most commonly those undergoing a conventional
      arthroplasty articulation. The estimated cost of a proximal femoral replacement
      is 18,002 pounds at our centre. Less than half of this is reimbursed under
      Payment by Results. Endoprosthetic replacement of the proximal femur is an
      effective treatment of metastases, but is poorly reimbursed under current funding
      arrangements.

PMID- 19603166
TI  - Comparison of interface contact profiles of a new minimum contact locking
      compression plate and the limited contact dynamic compression plate.
AB  - In this study, we investigated whether or not a new minimum contact locking
      compression plate (MC-LCP) can provide advantages over the limited contact
      dynamic compression plate (LC-DCP) in the context of interface contact area and
      force. Six matched pairs of cadaveric bones were used for each of three bone
      types of the humerus, radius and ulna. For each bone type, one of two bone plates
      was fixed to either of two matched cadaveric bones at the middle of the
      diaphysis. The interface contact area and force of the plate fixed to three types
      of human cadaveric bones were evaluated using Fuji prescale pressure sensitive
      film. Data were quantitated using computer-assisted image analysis. Results
      showed that the average force between the MC-LCP and humerus or radius was about
      half of that of the LC-DCP. And the average force between the MC-LCP and ulna was
      one third less than that of the LC-DCP. Meanwhile, the interface contact area
      between the MC-LCP and humerus or radius was also about half of that of the LC
      DCP, and the interface contact area between the MC-LCP and ulna was less than one
      third of that of the LC-DCP. These results indicate that the MC-LCP has lower
      interface contact area and lower average force than that of the LC-DCP. Thus, the
      MC-LCP system may be a good alternate to treat forearm diaphyseal fractures.

PMID- 19603167
TI  - Aberrant expression of Notch signaling molecules in patients with immune
      thrombocytopenic purpura.
AB  - To investigate the role of Notch signaling pathway in immune thrombocytopenic
      purpura (ITP), we measured the expression of 11 Notch pathway molecules in ITP
      patients and evaluated their clinical relevance. Real-time reverse transcriptase
      polymerase chain reaction results showed there was aberrant expression of some
      Notch molecules in ITP. Notch1 and Notch3 expression elevated, while Notch2
      decreased statistically in ITP patients. As for Notch ligands, only DLL1 was
      found downregulated in ITP. The expression of Notch target gene, Hes1, was also
      upregulated. In accordance with the mRNA level, Notch1 and Hes1 protein
      expression was also found elevated by Western blot. Immunocytochemistry showed
      that Notch1 expressed highly in the cytomembrane, cytoplasm, and part of cellular
      nucleus for ITP while weak in cytomembrane for controls, and Hes1 of ITP was
      found expressed higher in cellular nucleus than that of controls. Our findings
      suggest that the aberrant expression profile of Notch pathway may be involved in
      ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept.

PMID- 19603168
TI  - Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese
      and Caucasian healthy volunteers.
AB  - PURPOSE: Axitinib, a potent and selective inhibitor of vascular endothelial
      growth factor receptors 1, 2, 3, is metabolized by cytochrome P450 3A4 and
      glucuronidation. This study evaluated the effect of rifampin, a potent inducer of
      drug-metabolizing enzymes, on axitinib plasma pharmacokinetics. Equal numbers of
      Japanese and Caucasian subjects were enrolled to assess the potential differences
      in axitinib pharmacokinetics between the two ethnicities. METHODS: Forty healthy
      volunteers were randomized to receive 5 mg axitinib alone and with 600 mg
      rifampin. RESULTS: Rifampin expectedly decreased AUCinf and Cmax of axitinib
      (geometric mean reduced by 79 and 71%, respectively). However, differences in
      axitinib pharmacokinetics were not observed between Japanese and Caucasian
      subjects (geometric mean ratios for axitinib treatment alone for AUCinf and Cmax
      were 103 and 96%). CONCLUSIONS: The results support a common axitinib starting
      dose in both populations. Potent inducers of drug-metabolizing enzymes reduce
      axitinib exposure and dose adjustments may be needed for optimal efficacy.

PMID- 19603169
TI  - Old and rising stars in the lymphoid liver.

PMID- 19603171
TI  - Agrobacterium-mediated transformation of meadow fescue (Festuca pratensis Huds.).
AB  - Meadow fescue (Festuca pratensis Huds.) is an important cool-season forage grass
      in Europe and Asia. We developed a protocol for producing meadow fescue
      transgenic plants mediated by Agrobacterium tumefaciens transformation.
      Embryogenic calli derived from mature embryos were transformed with A.
      tumefaciens strain AGL1 carrying the binary vector pDM805, coding for the
      phosphinothricin acetyltransferase (bar) and beta-glucuronidase (uidA) genes.
      Bialaphos was used as the selective agent throughout all phases of tissue
      culture. In total, 40 independent transgenic plants were recovered from 45
      bialaphos-resistant callus lines and an average transformation efficiency of 2%
      was achieved. The time frame from infection of embryogenic calli with
      Agrobacterium to transferring the transgenic plants to the greenhouse was 18
      weeks. In a study of 11 BASTA-resistant transgenic lines, the uidA gene was
      expressed in 82% of the transgenic lines. Southern blot analysis revealed that
      82% of the tested lines integrated one or two copies of the uidA gene.

PMID- 19603173
TI  - Pyoderma gangrenosum after abdominal surgery--a rare but none the less necessary
      differential diagnosis.

PMID- 19603172
TI  - Management of the post chemotherapy subcentimeter residual mass: the case for
      observation.

PMID- 19603174
TI  - Comparative study of conventional colonoscopy, magnifying chromoendoscopy, and
      magnifying narrow-band imaging systems in the differential diagnosis of small
      colonic polyps between trainee and experienced endoscopist.
AB  - BACKGROUND: Removal of colorectal neoplastic polyps can reduce the incidence of
      colorectal cancers. It is important to distinguish neoplastic from nonneoplastic
      polyps. We compared the ability of a trainee and an experienced endoscopist in
      distinguishing between neoplastic polyps and nonneoplastic polyps by conventional
      white-light, magnifying narrow-band imaging (NBI), and magnifying
      chromoendoscopy. MATERIALS AND METHODS: One hundred and sixty-three small
      colorectal polyps from 104 patients were studied. All polyps were diagnosed by
      trainees and experienced endoscopists using conventional white-light, magnifying
      NBI, and magnifying chromoendoscopy. The kappa values of interobserver agreement
      between trainees and experienced endoscopists were evaluated before this study.
      Sensitivity, specificity, and diagnostic accuracy were assessed by reference to
      histopathology. The first 50 polyps were diagnosed by the trainee as the first
      stage and the rest 113 polyps were diagnosed as the second stage. RESULTS:
      Magnifying NBI and magnifying chromoendoscopy were significant better than
      conventional white-light by the experienced endoscopist (diagnostic accuracy: NBI
      85.3%, chromoendoscopy 87.7%, conventional view 74.8%). No significant
      differences were found for the trainee. The kappa values (0.77 approximately
      0.85) were good for each endoscopic modality for the experienced endoscopist.
      However, only NBI and chromoendoscopy had acceptable kappa values (0.40
      approximately 0.48) for the trainee. The trainee improved diagnostic accuracy in
      the second stage, but not yielded the level of the experienced endoscopist.
      CONCLUSION: Magnifying NBI and magnifying chromoendoscopy had a better
      interobserver agreement than conventional white-light among trainees and
      experienced endoscopists. The trainee needs learning time to improve diagnostic
      ability, even using a new modality such as magnifying NBI.

PMID- 19603176
TI  - Persistent mechanical linkage between sister chromatids throughout anaphase.
AB  - In budding yeast, we have found that sister rDNA arrays marked with fluorescent
      probes can be visualized as two distinguishable strands during metaphase. Upon
      anaphase, these arm loci are drawn into the spindle, where they adopt a cruciform
      like structure and stretch 2.5-fold as they migrate to the poles. Therefore,
      while sister rDNA arrays appear separated in metaphase, mechanical linkages
      between sister arm loci persist throughout anaphase in yeast, as shown in
      grasshopper spermatocytes (Paliulis and Nicklas 2004). These linkages are
      partially dependent on the protector of cohesin, SGO1. In anaphase, the spatially
      regulated dissolution of these mechanical linkages serves to prevent premature
      sister separation and restrain the rate of spindle elongation. Thus, sister
      separation is temporally controlled and linkages between sister chromatids
      contribute to the regulation of anaphase spindle elongation.

PMID- 19603175
TI  - Validity, reliability, and sensitivity-to-change properties of the psoriatic
      arthritis screening and evaluation questionnaire.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis associated with
      irreversible joint damage in a subset of individuals. There is a need to screen
      early for this condition to prevent damage. To meet this need, we have developed
      the psoriatic arthritis screening and evaluation (PASE) questionnaire. The 15
      item PASE questionnaire was administered to 190 individuals with either psoriasis
      or PsA. The PASE questionnaire was readministered to a subset of individuals with
      PsA in order to assess test-retest reliability and sensitivity-to-change.
      Receiver operator curves were constructed to optimize sensitivity and specificity
      for the diagnosis of PsA. Of the 190 participating in the study, 19.5% (37/191)
      participants were diagnosed with PsA. PASE total scores ranged from 15 to 74
      (possible range, 15-75). The PsA group had a median Total score of 51 (25th and
      75th percentile 44 and 57), and non-PsA group had a median total score of 34
      (25th and 75th percentile 21 and 49) (p < 0.001). A PASE total score of 44 was
      able to distinguish PsA from non-PsA participants with 76% sensitivity and 76%
      specificity. Furthermore, 13 of the 15 items demonstrated significant test-retest
      reliability as assessed by Pearson correlation coefficient (r >or= 0.5). PASE was
      sensitive-to-change with therapy; PASE scores were significantly lower for PsA
      individuals after systemic therapy (p < 0.034). The PASE questionnaire is a valid
      and reliable tool to screen for active PsA among individuals with psoriasis. PASE
      scores may be used as a marker of therapeutic response.

PMID- 19603178
TI  - Constitutive and oxidative-stress-induced expression of VEGF in the RPE are
      differently regulated by different Mitogen-activated protein kinases.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a fundamental factor for
      angiogenesis. It plays important roles in pathological conditions (e.g. the
      development of wet AMD), but also in the healthy organism) e.g. in maintaining
      the vasculature and supporting the retina). Recent therapies to treat the wet AMD
      focus on neutralizing VEGF indiscriminately. VEGF is constitutively expressed in
      the retina, but its expression is upregulated by various (noxious) stimuli, e.g.
      oxidative stress or hypoxia. Discrimination between constitutive expression of
      VEGF and its pathological upregulation might provide the possibility of focusing
      on inhibiting the pathological expression only. Here, we focused on the influence
      of different mitogen-activated protein kinase (MAPK) (p38, Erk, JNK) on the
      secretion and expression of VEGF, with or without being challenged by oxidative
      stress. METHODS: VEGF secretion was measured using a perfusion organ culture
      model; expression was examined in primary RPE culture and Western blotting.
      RESULTS: Constitutive VEGF expression and secretion can be diminished by
      inhibiting p38, while inhibiting Erk or JNK does not show a significant effect.
      When challenged with oxidative stress (250 microM t-butylhydroperoxide), VEGF
      expression and secretion increases and the influence of the MAPK changes: While
      p38 still accounts for about 30% of the secretion, Erk shows a similar influence.
      Inhibiting JNK presents conflicting results. In organ culture, inhibiting JNK
      significantly increases VEGF secretion after stimulation with 250 microM tBH,
      while with regard to VEGF expression in RPE cell culture, this effect could not
      be seen. CONCLUSION: Constitutive and oxidative stress induced VEGF secretion,
      and expression is differently regulated, which might offer an opportunity to
      selectively inhibit pathological VEGF expression only.

PMID- 19603170
TI  - Primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver
      disease with a slowly progressive course. Without treatment, most patients
      eventually develop fibrosis and cirrhosis of the liver and may need liver
      transplantation in the late stage of disease. PBC primarily affects women (female
      preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years
      of age. Common symptoms of the disease are fatigue and pruritus, but most
      patients are asymptomatic at first presentation. The diagnosis is based on
      sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase
      and gamma-glutamyl transferase, and the presence of serum antimitochondrial
      antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex.
      Histologically, PBC is characterized by florid bile duct lesions with damage to
      biliary epithelial cells, an often dense portal inflammatory infiltrate and
      progressive loss of small intrahepatic bile ducts. Although the insight into
      pathogenetic aspects of PBC has grown enormously during the recent decade and
      numerous genetic, environmental, and infectious factors have been disclosed which
      may contribute to the development of PBC, the precise pathogenesis remains
      enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical
      treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to
      two out of three patients with PBC may have a normal life expectancy without
      additional therapeutic measures. The mode of action of UDCA is still under
      discussion, but stimulation of impaired hepatocellular and cholangiocellular
      secretion, detoxification of bile, and antiapoptotic effects may represent key
      mechanisms. One out of three patients does not adequately respond to UDCA therapy
      and may need additional medical therapy and/or liver transplantation. This review
      summarizes current knowledge on the clinical, diagnostic, pathogenetic, and
      therapeutic aspects of PBC.

PMID- 19603179
TI  - Complementary developmental expression of the two tyrosine hydroxylase
      transcripts in zebrafish.
AB  - Tyrosine hydroxylase (TH) is a rate-limiting enzyme in the biosynthesis of
      catecholamines. In zebrafish, two genes encoding TH have been identified. We
      cloned them and studied their expression in zebrafish. In adult tissues, th1 mRNA
      was more abundant than th2 mRNA in the brain and eyes, whereas th2 mRNA was more
      abundant in the liver, kidney, heart and gills. In developing brain, th1 mRNA was
      readily detected at 1 day post-fertilization using qPCR and in situ
      hybridization, whereas th2 mRNA appeared later. th1 was found in 17
      catecholaminergic groups in larval brain, whereas th2 was found in four
      additional groups. A monoclonal antibody commonly used against TH detected
      preferentially TH1 protein. The two th genes, probably originated as a result of
      genome duplication, thus show complementary expression, although th1 is
      predominant in the brain and th2 in the periphery. th2 may be a novel essential
      factor in regulation of catecholamine synthesis in zebrafish.

PMID- 19603180
TI  - Distinct non-target site mechanisms endow resistance to glyphosate, ACCase and
      ALS-inhibiting herbicides in multiple herbicide-resistant Lolium rigidum.
AB  - This study investigates mechanisms of multiple resistance to glyphosate, acetyl
      coenzyme A carboxylase (ACCase) and acetolactate synthase (ALS)-inhibiting
      herbicides in two Lolium rigidum populations from Australia. When treated with
      glyphosate, susceptible (S) plants accumulated 4- to 6-fold more shikimic acid
      than resistant (R) plants. The resistant plants did not have the known glyphosate
      resistance endowing mutation of 5-enolpyruvylshikimate-3 phosphate synthase
      (EPSPS) at Pro-106, nor was there over-expression of EPSPS in either of the R
      populations. However, [(14)C]-glyphosate translocation experiments showed that
      the R plants in both populations have altered glyphosate translocation patterns
      compared to the S plants. The R plants showed much less glyphosate translocation
      to untreated young leaves, but more to the treated leaf tip, than did the S
      plants. Sequencing of the carboxyl transferase domain of the plastidic ACCase
      gene revealed no resistance endowing amino acid substitutions in the two R
      populations, and the ALS in vitro inhibition assay demonstrated herbicide
      sensitive ALS in the ALS R population (WALR70). By using the cytochrome P450
      inhibitor malathion and amitrole with ALS and ACCase herbicides, respectively, we
      showed that malathion reverses chlorsulfuron resistance and amitrole reverses
      diclofop resistance in the R population examined. Therefore, we conclude that
      multiple glyphosate, ACCase and ALS herbicide resistance in the two R populations
      is due to the presence of distinct non-target site based resistance mechanisms
      for each herbicide. Glyphosate resistance is due to reduced rates of glyphosate
      translocation, and resistance to ACCase and ALS herbicides is likely due to
      enhanced herbicide metabolism involving different cytochrome P450 enzymes.

PMID- 19603181
TI  - Between-person effects on attention and action: Joe and Fred revisited.
AB  - Previous study indicates that target-target inhibition of return (IOR) is not
      restricted to a single nervous system. Specifically, watching another person
      perform a goal-directed aiming movement engages similar inhibitory processes on a
      subsequent aiming attempt as if having performed the preceding movement oneself.
      This between-person effect has been attributed to the mirror neuron system. In
      the study reported here, we replicated this finding and examined the relative
      importance of automatic stimulus alerting events and action-observation by
      dissociating these two influences. This was done by having two people alternately
      perform sets of two aiming trials to the same equally probable targets. Under
      some experimental conditions, one or both of the performers moved to a non
      illuminated target. In this way, we dissociated the stimulus and observed event
      under some between-person conditions. Although IOR was greatest when the stimulus
      and observed events were compatible, both contributed to the between-person
      inhibitory processes slowing the responses (Experiment 1). The impact of
      observing another person perform an aiming movement appears to have more to do
      with realizing a particular spatial goal than seeing the biological motion
      associated with achieving that goal (Experiment 2). Findings that both the
      illumination of a visual target signal and the observation of another person's
      action engage similar attention-action processes are consistent with action-based
      accounts of visual selective attention.

PMID- 19603182
TI  - Genetic variability of Blastocystis sp. isolates obtained from cancer and
      HIV/AIDS patients.
AB  - This represents the first study to determine the genetic diversity of
      Blastocystis sp. among cancer and HIV/AIDS patients. Forty Blastocystis sp.
      isolates obtained from 20 cancer and 20 HIV/AIDS patients were genotyped by PCR
      using seven pairs of known sequenced-tagged site primers. Out of the 40 isolates,
      38 were identified as one of the known genotypes and two isolates were negative
      with all the STS primers. Blastocystis sp. subtype 3 which is reported to be
      associated with disease was found to be predominant among the study subjects.

PMID- 19603185
TI  - Post-transcriptional silencing of the Drosophila homolog of human ZASP: a
      molecular and functional analysis.
AB  - In humans, mutations in ZASP (the gene for Z-band alternatively spliced PDZ-motif
      protein) are associated with dilated cardiomyopathy and left ventricular non
      compaction. In particular, mutations in or around the Zasp motif seem to be
      related to myofibrillar myopathy. Thus, "zaspopathies" include symptoms such as Z
      line disgregation, proximal and distal muscle weakness, cardiomyopathies, and
      peripheral neuropathies. In order to understand the role of ZASP in muscle
      structure and function, we have performed a molecular characterization of the
      Drosophila ortholog of human ZASP and a functional analysis following the post
      transcriptional silencing of the Drosophila gene. Transcriptional analysis of
      dzasp has revealed six additional exons, with respect to the known 16, and
      multiple splice variants. We have produced transgenic lines harboring constructs
      that, through the use of the UAS/Gal4 binary system, have enabled us to drive
      dsRNA interference of dzasp in a tissue-specific manner. Knockdown individuals
      show locomotor defects associated with alterations of muscle structure and
      ultrastructure, consistent with a role of dzasp specifically in the maintenance
      of muscular integrity.

PMID- 19603183
TI  - Helix 69 in 23S rRNA modulates decoding by wild type and suppressor tRNAs.
AB  - Helix 69 of 23S rRNA forms one of the major inter-subunit bridges of the 70S
      ribosome and interacts with A- and P-site tRNAs and translation factors. Despite
      the proximity of h69 to the decoding center and tRNAs, the contribution of h69 to
      the tRNA selection process is unclear: previous genetic analyses have shown that
      h69 mutations increase frameshifting and readthrough of stop codons. However, a
      complete deletion of h69 does not affect the selection of cognate tRNAs in vitro.
      To address these discrepancies, the in vivo effects of a range of single- and
      multi-base h69 mutations in Escherichia coli 23S rRNA on various translation
      errors have been determined. While a majority of the h69 mutations examined here
      affected readthrough of stop codons and frameshifting, the DeltaA1916 single base
      deletion mutation uniquely influenced missense decoding. Different h69 mutants
      had either increased or decreased levels of stop codon readthrough. The h69
      mutations that decreased UGA readthrough also decreased UGA reading by a mutant,
      near-cognate tRNA(Trp) carrying a G24A substitution in the D arm, but had far
      less effect on UGA reading by a suppressor tRNA with a complementary anticodon.
      These results suggest that h69 interactions with release factors contribute
      significantly to termination efficiency and that interaction with the D arm of A
      site tRNA is important for discrimination between cognate and near-cognate tRNAs.

PMID- 19603184
TI  - Carboxypeptidase E, an essential element of the regulated secretory pathway, is
      expressed and partially co-localized with chromogranin A in chicken thymus.
AB  - Although the functions of hormones and neuropeptides in the thymus have been
      extensively studied, we still do not know whether these intra-thymic humoral
      elements are released in a stimulated manner via the regulated secretory pathway
      or in a constitutive manner. Carboxypeptidase E (CpE) and chromogranin A (CgA)
      are functional and structural hallmarks of the regulated secretory pathway in
      (neuro)endocrine cells. Whereas we have previously shown a CgA-positive
      neuroendocrine population in the chicken thymus, the current study assesses the
      expression of CpE in the thymus, both at the mRNA and the protein level. Our
      immunohistochemical studies provide evidence for the co-existence of CgA and CpE
      in identical neuroendocrine cells in the thymus. CpE and CgA dual-positive cells
      have primarily been found in the transition zone between the cortex and medulla
      of the thymus, an area known to contain numerous arterioles and to be innervated
      by the autonomic nervous system. Our findings suggest that the diffuse
      neuroendocrine system serves as a relay for nervous stimuli delivered by the
      sympathetic and/or parasympathetic nervous system. Thus, these newly defined
      neuroendocrine cells might play an important role in the immuno-neuro-endocrine
      cross-talk in the thymus, potentially enabling thymopoiesis to be fine-tuned via
      the regulated secretory pathway by a variety of physical and environmental
      factors.

PMID- 19603187
TI  - Chiral resolution of phenylalanine by D-Phe imprinted membrane considering
      rejection property.
AB  - An enantio-selective D-Phe imprinted P(AA-co-AN) membrane was prepared using the
      wet-phase inversion method. The membrane not only selectively adsorbed
      phenylalanine but also rejected it with a rejection selectivity of 0.82-0.64 and
      0.91-0.63 during the filtration of 100 and 10 ppm (g m(-3)) racemate solutions,
      respectively. The fluxes of D-Phe and L-Phe during filtration of 10 ppm racemate
      solution were 0.0077-0.0229 and 0.0064-0.0208 mg m(-2) s(-1), respectively, and
      the fluxes of D-Phe and L-Phe during filtration of 100 ppm racemate solution were
      0.1287-0.2522 and 0.1174-0.2458 mg m(-2) s(-1), respectively. The adsorption
      selectivity was higher at low concentration. The adsorption selectivities varied
      from 1.11 to 1.65 and from 1.64 to 2.78 during filtration of 100 and 10 ppm
      racemate solutions, respectively. In respect to desorption, the fractional
      difference between D-Phe and L-Phe in the recovered solution from 10 ppm was
      higher than that from 100 ppm.

PMID- 19603186
TI  - Impact of simulated herbivory on water relations of aspen (Populus tremuloides)
      seedlings: the role of new tissue in the hydraulic conductivity recovery cycle.
AB  - Physiological mechanisms behind plant-herbivore interactions are commonly
      approached as input-output systems where the role of plant physiology is viewed
      as a black box. Studies evaluating impacts of defoliation on plant physiology
      have mostly focused on changes in photosynthesis while the overall impact on
      plant water relations is largely unknown. Stem hydraulic conductivity (k(h)),
      stem specific conductivity (k(s)), percent loss of hydraulic conductivity (PLC),
      CO(2) assimilation (A) and stomatal conductance (g(s)) were measured on well
      irrigated 1-month-old Populus tremuloides (Michx.) defoliated and control
      seedlings until complete refoliation. PLC values of defoliated seedlings
      gradually increased during the refoliation process despite them being kept well
      irrigated. k(s) of defoliated seedlings gradually decreased during refoliation.
      PLC and k(s) values of control seedlings remained constant during refoliation.
      k(s) of new stems, leaf specific conductivity and A of leaves grown from new
      stems in defoliated and control seedlings were not significantly different, but
      g(s) was higher in defoliated than in control seedlings. The gradual increase of
      PLC and decrease of k(s) values in old stems after defoliation was unexpected
      under well-irrigated conditions, but appeared to have little impact on new stems
      formed after defoliation. The gradual loss of conductivity measured during the
      refoliation process under well-irrigated conditions suggests that young seedlings
      of P. tremuloides may be more susceptible to cavitation after herbivore damage
      under drought conditions.

PMID- 19603188
TI  - Post-renal transplantation hypophosphatemia.
AB  - An understanding of the pathophysiologic mechanisms of post-renal transplant
      (PRT) bone disease is of important clinical significance. Although bone disease
      occurs after all solid organ transplantation, the cumulative skeletal fracture
      rate remains high in PRT subjects while reaching a plateau with other
      transplantations. One major difference in the pathophysiology of PRT bone disease
      is, perhaps, due to persistent renal phosphorus (Pi) wasting. Novel phosphaturic
      agents have recently been suggested to participate in the development of bone
      disease in PRT subjects. However, it is unclear as of yet whether these factors
      alone or in conjunction with excess parathyroid hormone (PTH) secretion play a
      key role in the development of negative Pi balance and consequent bone disease in
      this population. In this review, I present a natural history of PRT
      hypophosphatemia and persistent renal Pi leak, provide pathophysiologic insight
      into these developments, and discuss the difficulty in diagnosing these
      phenotypes in both adult and pediatric populations.

PMID- 19603189
TI  - Advances in urinary proteome analysis and biomarker discovery in pediatric renal
      disease.
AB  - Recent progress in proteomic analysis and strategies for the identification of
      clinically useful biomarkers in biofluids has led to the identification of urine
      as an excellent non-invasive reservoir for biomarkers of disease. Urinary
      biomarkers have been identified and validated on independent cohorts in different
      high-incidence adult renal diseases, including diabetic nephropathy, chronic
      kidney disease and immunoglobulin A-nephropathy, but also in extrarenal disease,
      such as coronary artery disease. Unfortunately, this type of research is
      underrepresented in the pediatric population. Here, we present the rare studies
      in the pediatric population that identified potential clinically useful urinary
      biomarkers in ureteropelvic junction (UPJ) obstruction and renal Fanconi
      syndrome. These studies, although limited in number, clearly show the potential
      of urinary proteomics, especially in the pediatric population. It is anticipated
      that the advances made in the adult population, the lessons learned on the use of
      appropriate statistics and the inclusion of independent blinded validation
      cohorts in these types of studies will rapidly lead to clinical useful urinary
      biomarkers for other pediatric (renal) disease in a population where non-invasive
      analysis is particularly appreciated.

PMID- 19603190
TI  - Official positions of the International Society for Clinical Densitometry (ISCD)
      on DXA evaluation in children and adolescents.
AB  - Dual-energy X-ray absorptiometry (DXA) is the most widely used technical
      instrument for evaluating bone mineral content (BMC) and density (BMD) in
      patients of all ages. However, its use in pediatric patients, during growth and
      development, poses a much more complex problem in terms of both the technical
      aspects and the interpretation of the results. For the adults population, there
      is a well-defined term of reference: the peak value of BMD attained by young
      healthy subjects at the end of skeletal growth. During childhood and adolescence,
      the comparison can be made only with healthy subjects of the same age, sex and
      ethnicity, but the situation is compounded by the wide individual variation in
      the process of skeletal growth (pubertal development, hormone action, body size
      and bone size). The International Society for Clinical Densitometry (ISCD)
      organized a Pediatric Position Development Conference to discuss the specific
      problems of bone densitometry in growing subjects (9-19 years of age) and to
      provide essential recommendations for its clinical use.

PMID- 19603191
TI  - Limitations of dual x-ray absorptiometry in children with chronic kidney disease.
AB  - Dual x-ray absorptiometry (DXA) is the most widely used densitometric method for
      diagnosing osteoporosis in adults. It has also been widely adopted as a
      diagnostic tool in the pediatric population. The most significant limitation of
      DXA is its reliance on areal rather than volumetric bone mineral density (BMD),
      which results in an artificial underestimation of bone density in short people.
      Poor longitudinal growth, however, is an eminent problem in children with chronic
      kidney disease (CKD). There is also no evidence in children that areal BMD is
      predictive of future fracture risk, which is the traditional rationale for
      measuring BMD in children with CKD. Therefore, the Kidney Disease Outcomes
      Quality Initiative guidelines and the current position of the International
      Society for Clinical Densitometry (ISCD) on pediatric patients, both of which are
      presented in this issue of Pediatric Nephrology, do not recommend the use of DXA
      in children with CKD. To date, there is no consensus on the best method to assess
      the degree of renal osteodystrophy in this patient population, and further
      collaborative efforts to correlate densitometric findings with clinical outcomes
      are warranted.

PMID- 19603193
TI  - Cytomegalovirus infection and haemophagocytosis in a patient with congenital
      nephrotic syndrome.
AB  - Congenital nephrotic syndrome is a rare clinical entity defined as massive
      proteinuria leading to symptoms within the infant's first 3 months of life.
      Although the association between congenital nephrotic syndrome and
      cytomegalovirus infection has been identified, association with haemophagocytosis
      has not been reported in the literature. In this case report we describe
      concomitant cytomegalovirus infection and haemophagocytosis in a 3-month-old girl
      with congenital nephrotic syndrome.

PMID- 19603192
TI  - Fetal development and renal function in adult rats prenatally subjected to sodium
      overload.
AB  - The aims of this study were (1) to evaluate two factors that affect fetal
      development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with
      sodium overload and (2) to correlate possible alterations in these factors with
      subsequent modifications in the renal function of adult offspring. Wistar dams
      were maintained on 0.17 M NaCl instead of water from 20 days before mating until
      either the twentieth pregnancy day/parturition or weaning. Colorimetric methods
      were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary
      protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol).
      Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood
      pressure transducer, a flow probe and inulin clearance to measure mean arterial
      pressure (MAP), renal blood flow and glomerular filtration rate (GFR),
      respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams
      showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h)
      (150%, P < 0.05). Prenatally sodium-overloaded pups showed increased U(Prot24 h)
      (45%, P < 0.05) but unchanged MAP, renal hemodynamics, NN and kidney Ox.
      Prenatally and postnatally sodium-overloaded rats showed increased U(Prot24 h)
      (27%, P < 0.05) and kidney Ox (44%, P < 0.05), reduced GFR (12%, P < 0.05),
      increased PV (26%, P < 0.05) and unchanged MAP and NN. The TG increased in both
      groups of treated offspring (21%, P < 0.05), whereas Chol increased only in the
      postnatally sodium-overloaded group. We conclude that salt overload from the
      prenatal stage until weaning leads to alterations in lipid metabolism and in the
      renal function of the pups, which are additional to those alterations seen in
      rats only overloaded prenatally.

PMID- 19603194
TI  - Mid-aortic syndrome: long-term outcome of 36 children.
AB  - The clinical characteristics and outcomes of children with mid-aortic syndrome
      (MAS) and the effectiveness of different therapeutic approaches in reducing
      hypertension are still debated. We conducted a single-centre retrospective review
      of the records of children with MAS over 30 years. Children with angiographic
      evidence of a narrowed abdominal aorta were included. Therapeutic approaches
      included medical management, percutaneous transluminal angioplasty and/or
      surgical intervention. Thirty-six children had presented at a median age of 2.7
      years (10 days-10 years). Thirteen (36%) patients had associated syndromes, and
      44% had been diagnosed with cerebrovascular disease. All patients had involvement
      of multiple arteries. The mortality rate was 8% after a median follow-up period
      of 4.5 (range 1.1-19.7) years. Among the children who survived, 90% had obtained
      a reduction in their blood pressure (BP). Of the patients, 76% had had a normal
      estimated glomerular filtration rate (eGFR) at the last follow-up examination.
      Seventeen percent (six of 36) had renal dysfunction at presentation. Although MAS
      is a severe and widespread disease, in most cases it can be effectively treated
      with a combination of medical, angioplasty and surgical interventions.

PMID- 19603195
TI  - ACE gene insertion/deletion polymorphism and renal scarring in children with
      urinary tract infections.
AB  - Urinary tract infection is a common bacterial disease that presents during
      childhood and may lead to renal scarring. Several studies have shown a strong
      association between the angiotensin converting enzyme (ACE) deletion polymorphism
      and renal scarring in children with vesicoureteric reflux (VUR). The purpose of
      this study was to investigate the possible correlation between the ACE deletion
      polymorphism and renal scarring in 186 children with urinary tract infection
      (UTI), of whom 90 were renal scar positive and 96 were renal scar negative. The
      control group consisted of 129 children with no UTI. Renal scars were diagnosed
      by means of (99m)Tc-dimercapto-succinic acid scans, and ACE genotypes were
      determined as II, ID, and DD by PCR analyses. The ACE genotype distribution was
      10% II, 67% ID, and 23% DD in the renal scar-positive group, 18% IotaIota, 42%
      ID, and 40% DD in the renal scar-negative group, and 22% II, 47% ID, and 31% DD
      in the control group. No correlation was found between the DD genotype and renal
      scar formation in children with UTI. The same results were obtained following
      strafication of the patients by VUR and age of the first urinary tract infection.
      In conclusion, the results of this study suggest that the DD genotype is not an
      independent risk factor for renal scarring in children with UTI.

PMID- 19603196
TI  - Clinical and metabolic features of urolithiasis and microlithiasis in children.
AB  - We evaluated the clinical, radiological and metabolic features of 162 children
      with urolithiasis or microlithiasis who had been referred to our pediatric
      nephrology clinics between 1998 and 2008 with suspected urolithiasis. The medical
      histories of these children (78 girls, 84 boys), who ranged in age from 2 months
      to 16 years (mean age 5.59 +/- 0.35 years), were reviewed retrospectively for
      clinical and metabolic features of urinary tract calculi. Urinary tract
      infections (UTI) were present in 45.9% of the cases. The most common presenting
      symptoms were flank pain or restlessness (25.3%) and hematuria (21.6%), followed
      by UTI (16%), whereas 23.5% of the cases were detected incidentally during
      evaluation for other medical conditions. Other symptoms at presentation included
      dysuria, passing stones, penile edema, enuresis, vomiting and anorexia. Urine
      analysis revealed metabolic abnormalities in 87% of the cases, including
      hypercalciuria (33.8%), hypocitraturia (33.1%), hyperoxaluria (26.5%),
      hyperuricosuria (25.4%), hypocitraturia + hypercalciuria (21.1%),
      hyperphosphaturia (20.8%) and cystinuria (5.7%). Almost 50% of the patients had a
      positive family history for urolithiasis. The most frequently involved site was
      in the kidneys (86%). Ureters and bladder were involved in 12 and 2% of the
      cases, respectively. A family history of urolithiasis, presenting symptoms and
      underlying metabolic abnormalities were similar for microlithiasis and the
      patients with larger stones. However, in our study population, microlithiasis was
      mainly a disease of young infants, with a greater chance for remission and often
      not associated with structural changes. The presenting symptoms of urolithiasis
      show a wide spectrum, so that a high index of suspicion is important for early
      detection. A metabolic abnormality can be identified in 87% of cases of
      urolithiasis. Detection of microlithiasis may explain a number of symptoms, thus
      reducing invasive diagnostic procedures and allowing early recognition of
      metabolic abnormalities. These results draw attention to the importance of
      screening for UTIs in patients with urolithiasis.

PMID- 19603197
TI  - Cervical synovial cyst: case report and review of literature.
AB  - Synovial cysts, typically observed in the lumbar spine eventually associated with
      degenerative changes of the facet joints, only rarely present in the cervical
      spine. Up to now, only 28 symptomatic cases are described in literature.
      Typically, the treatment of these cases is a decompressive laminectomy followed
      by complete surgical removal of the lesion. The authors present the case of an 84
      year-old man with a symptomatic synovial cyst involving the space between C7 and
      T1.

PMID- 19603198
TI  - Nucleus pulposus tissue engineering: a brief review.
AB  - Symptomatic intervertebral disc degeneration is associated with several spinal
      diseases, which cause losses of life quality and money. Tissue engineering
      provides a promising approach to recover the functionality of the degenerative
      intervertebral disc. Most studies are directed toward nucleus pulposus (NP)
      tissue engineering because disc degeneration is believed to originate in NP
      region, and considerable progress has been made in the past decade. Before this
      important technique is utilized for clinical treatment of disc degeneration, many
      challenges need to address including in all three principal components of tissue
      engineering, i.e., seed cells, signals and biomaterial scaffolds. This article
      briefly gives certain aspects of state of the art in this field, as well as pays
      a little more attention to our work published in the past 5 years, on growth and
      differentiation factor-5 (GDF-5), adipose-derived stem cells (ADSCs) and heparin
      functionalization of scaffold. We suggest that combinatorial application of
      ADSCs, GDF-5, heparin functionalization and injectable hydrogels will be
      advantageous in NP tissue engineering.

PMID- 19603199
TI  - Uptake of diterbium transferrin, a potential multi-photon-excited microscopy
      probe, into human leukemia K562 cells via a transferrin-receptor-mediated
      process.
AB  - Our present study provided new evidence for diterbium transferrin (Tb(2)Tf) as a
      potential multi-photon-excited microscopy probe. It indicated that the Tb(2)Tf
      complex can be transported into human leukemia K562 cells via a process mediated
      by transferrin (Tf) receptors as an intact entity and with no obvious cellular
      toxicity. The supporting evidence includes the following. First, the transport
      kinetic behavior of Tb was compared with that of the Tf moiety. The Tb was
      determined by inductively coupled plasma mass spectrometry and Tf was determined
      by fluorescence activated cell sorting analysis. The kinetic synchronization of
      internalization of both Tb and Tf into human leukemia K562 cells demonstrated the
      Tb(2)Tf complex was transported into cells as a whole. Second, using confocal
      laser scanning microscopy, we observed the localization of Tb(2)Tf in the cell.
      This showed that the internalized Tb(2)Tf was mostly situated in the same
      perinuclear region as diferric transferrin (Fe(2)Tf). In addition, pretreatment
      with pronase largely abolished the transport process of Tb(2)Tf. The relative
      fluorescence intensities representing the uptake of Tf into the cells decreased
      to about 16% and the cytosolic Tb content decreased to almost the same percentage
      as for Tf. Furthermore, the addition of Fe(2)Tf can effectively inhibit transport
      of Tb(2)Tf into K562 cells. Third, no significant decrease of cell viability was
      observed in the presence of Tb(2)Tf even for 24 or 48 h by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, prospects for the use of
      Tb(2)Tf as a multi-photon-excited microscopy probe in a living system are
      discussed.

PMID- 19603200
TI  - Randomised study for the 1-year crestal bone maintenance around modified diameter
      implants with different loading protocols: a radiographic evaluation.
AB  - This study evaluated by standardised digitised periapical radiography the crestal
      bone maintenance around modified diameter internal hex implants with variable
      thread design and narrow neck loaded with different procedures. Forty implants
      were placed in 25 patients. Twenty implants were conventionally loaded, 20 ones
      immediately loaded. Radiographs were taken with a customised bite record and
      processed with software. Measurements of bone from the fixture-abutment junction
      to mesial and distal marginal bone levels were made. Student's t test statistical
      analysis was adopted. Baseline data were variable; at 1-year follow-up, there
      were no significant differences for marginal bone loss between immediately and
      conventionally loaded maxillary implants (p = 0.1031), whilst there were slight
      significant differences between immediately and conventionally loaded implants in
      the mandible (p = 0.0141). Crestal bone maintenance around conventionally and
      immediately loaded modified diameter implants was similar, with slight
      significant differences in mandible where a lower marginal bone loss was
      observed.

PMID- 19603201
TI  - Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with
      computerized tomography presentation.
AB  - The aim of this study was to correlate clinical and computerized tomography (CT)
      features of bisphosphonate-related osteonecrosis of the jaws (BRONJ). All ONJ
      patients for whom there was complete CT scan imaging were eligible. Selected
      clinical parameters retrieved from their medical records were analyzed for
      correlation with CT parameters. The clinical presentation of BRONJ was supported
      by findings in CT imaging in 78.3%. The lesion's size on CT correlated with the
      presence of purulent secretion (p = 0.03). When sequestrum was present, the
      median lesion's size on CT was relatively big (28 mm, range 21-43 mm). The
      mandibular canal cortex was never breached. CT has reasonable detection
      competence for diagnosing BRONJ. Purulent secretion indicates the likelihood that
      a more extensive involvement will be displayed on CT. A large lesion on CT should
      raise the index of suspicion for sequestrum. The CT appearance of a continuous
      cortex of the mandibular canal may serve as a differential parameter between
      BRONJ and metastasis to the jaw.

PMID- 19603202
TI  - Factor analysis of microbiological activity data and structural parameters of
      antibacterial quinolones.
AB  - Factor analysis (FA) was performed on quinolone derivatives with antibacterial
      activity to model relationships between molecular descriptors and microbiological
      activities determined on five bacterial cell lines (Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus
      pneumoniae). Molecular modeling studies were performed with the use of HyperChem
      software and MM+ molecular mechanics with the semi-empirical AM1 method. Factor
      analysis led to the extraction of two main factors, with the share of factor 1
      amounting to about 76% and factor 2 to about 24% for all the parameters used in
      the statistical analysis. Moreover, FA results indicated that energy of orbitals
      lowest unoccupied molecular orbital, energy of ionization, electron affinity,
      electronegativity, maximum electron density, refraction and polarizability
      appeared to be descriptors important for the antibacterial activity of
      quinolones.

PMID- 19603204
TI  - Theoretical description of bonding in cis-W(CO)(4)(piperidine)(2) and its dimer.
AB  - The gradient-corrected DFT calculations were applied to characterize the bonding
      in the cis-W(CO)(4)(piperidine)(2) complex and its dimer. The Nalewajski-Mrozek
      bond order analysis, the Ziegler-Rauk bond-energy partitioning and Natural
      Orbitals for Chemical Valence (NOCV's) were applied in a description of the
      electronic structure of cis-W(CO)(4)(piperidine)(2). The results indicate that
      the metal-carbon bond trans to piperidine is stronger than that in the cis
      position, as a result of an increase in both, the ligand--> metal donation and
      metal --> ligand pi-back-bonding; this implies a weakening of the carbon-oxygen
      bond. In the dimeric complex, modeling the interactions in the solid state, the C
      O bond is further weakened resulting in the lowering the CO stretching
      frequencies, observed experimentally by Braunstein et al. (Angew. Chem. Int. Ed.
      (2004), 43:5922-5925).

PMID- 19603205
TI  - Molecule design and screening of novel unsymmetrical zinc phthalocyanine
      sensitizers for dye-sensitized solar cells.
AB  - The molecular orbital and optical properties of the dyes PCH001 and TT1 reported
      previously were studied using the density functional theory (DFT) and time
      dependent density functional theory (TDDFT) calculations. The results show that
      the electronic spectra simulated for PCH001 and TT1 in ethanol were in good
      agreement with the experimental data. The molecular orbital spatial orientation
      was used to interpret the discrepancy of the photovoltaic performances of the
      PCH001 and TT1 sensitized solar cells. The conjugation between the carboxyl group
      and the phthalocyanine ring in TT1 was found to be better than that through the C
      C single bond in PCH001, which may contribute to TT1's improved performance. Four
      new unsymmetrical phthalocyanine molecules with the peripheral substituents as
      donors and anchoring groups as acceptors, namely CZ1, CZ2, trans- and cis-CZ3,
      were designed and compared to PCH001 and TT1. The new molecules CZ2 and cis-CZ3
      were promising and may challenge the current record of PCH001 and TT1 in
      phthalocyanine-sensitized solar cells.

PMID- 19603203
TI  - Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a
      molecular docking analysis.
AB  - A molecular docking investigation has been carried out on cytotoxic prenylated
      flavonoids from Lonchocarpus haberi with cancer-relevant chemotherapeutic targets
      known to be inhibited by flavonoids. Two molecular docking programs, Molegro and
      ArgusDock, were used to compare the binding energies of Lonchocarpus flavonoids
      with other flavonoids, inhibitors, or known ligands, to aromatase (CYP 19), fatty
      acid synthase (FAS), xanthine oxidase (XO), cyclooxygenases (COX-1 and COX-2),
      lipoxygenase (LOX-3), ornithine decarboxylase (ODC), protein tyrosine kinase
      (PTK), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), topoisomerase II
      (ATP binding site), ATP binding cassette (ABC) transporter, and phospholipase
      A(2) (PLA). The Lonchocarpus flavonoids examined in this study exhibited docking
      energies comparable to or stronger than other flavonoids that had been previously
      shown to be effective inhibitors of these enzymes. Furthermore, prenylated
      flavonoids, such as the Lonchocarpus flavonoids and xanthohumol, generally showed
      greater binding energies than the non-prenylated flavonoids. We conclude,
      therefore, that the Lonchocarpus flavonoids possibly owe their cytotoxic activity
      by inhibition of one or more of these enzymes.

PMID- 19603207
TI  - A novel canine model of acute pyogenic spondylodiscitis.
AB  - New, appropriate in vivo animal models are needed for the study of the
      pathogenesis of spinal infections and the development of novel anti-infection
      strategies. The purpose of this study was to develop a canine model of acute
      pyogenic spondylodiscitis which can best mimic the human spinal infection
      process, characterized by separately inoculating bacterial suspension into the
      lumbar intervertebral spaces of a single animal. A total of 14 dogs were used in
      this study. An inoculation containing Staphylococcus aureus and sodium morrhuate
      was injected into the intervertebral spaces. Two pilot studies were carried out
      to determine the most appropriate concentration of the bacterium inoculum. Before
      the inoculation, the intervertebral disks were partially removed and the end
      plates of the adjacent two vertebrae were deliberately curetted out to make space
      for the inoculum and to more thoroughly expose the neighboring vertebrae to the
      bacterial inoculum. The dogs were euthanized at 14 days postimplantation. The
      bacterial loads of the infected tissues were assayed. Spondylodiscitis of the
      lumbar spinal column was consistently produced in 90% (nine out of ten) of the
      sites challenged with 10(2) colony-forming units (CFU) of S. aureus. Liver biopsy
      and blood culture did not show signs of systematic infections at 14 days
      postsurgery. Two out of four animals implanted with the suspension at a
      concentration higher than 10(3) CFUs were dead within 3 days postimplantation.
      The results indicate that this new canine model of acute pyogenic
      spondylodiscitis could be used to test the efficacy of different anti-infection
      strategies.

PMID- 19603206
TI  - Feasibility of collecting self-sampled vaginal swabs by mail: quantity and
      quality of genomic DNA.
AB  - Vaginal self-sampling may be valuable as an alternative method of cervical cancer
      screening in areas of poor resources, to enroll women who, otherwise, would not
      participate in population-based cervical cancer screening and in epidemiological
      follow-up studies. We assessed the reliability of mailed vaginal samples by
      evaluating the quantity and quality of genomic DNA in the samples. Mailed swabs
      (n = 201) were compared with freshly collected samples (n = 200) for DNA
      concentration (45.1 versus 50.9 ng/microl, respectively) and purity (mean optical
      density [OD] 260/280 ratio 1.88 versus 1.78, respectively). A small, non
      significant, decrease in DNA yield with longer transport time was noted. The DNA
      yield of mailed samples was significantly lower compared to fresh samples (P <
      0.002), but this lower yield had little effect on polymerase chain reaction (PCR)
      amplification. In conclusion, the large majority of mailed self-sampled vaginal
      swabs resulted in DNA of adequate purity and concentration for further research.

PMID- 19603208
TI  - Pulling an adsorbed polymer chain off a solid surface.
AB  - The thermally assisted detachment of a self-avoiding polymer chain from an
      adhesive surface by an external force applied to one of the chain-ends is
      investigated. We perform our study in the "fixed height" statistical ensemble
      where one measures the fluctuating force, exerted by the chain on the last
      monomer when a chain-end is kept fixed at height h over the solid plane at
      different adsorption strength [Formula: see text]. The phase diagram in the h
      [Formula: see text] plane is calculated both analytically and by Monte Carlo
      simulations. We demonstrate that in the vicinity of the polymer desorption
      transition a number of properties like fluctuations and probability distribution
      of various quantities behave differently, if h rather than f is used as an
      independent control parameter.

PMID- 19603209
TI  - Evidence of a two-state picture for supercooled water and its connections with
      glassy dynamics.
AB  - The picture of liquid water as consisting of a mixture of molecules of two
      different structural states (structured, low-density molecules and unstructured,
      high-density ones) represents a belief that has been around for long time
      awaiting for a conclusive validation. While in the last years some indicators
      have indeed provided certain evidence for the existence of structurally different
      "species", a more definite bimodality in the distribution function of a sound
      structural quantity would be desired. In this context, our present work combines
      the use of a structural parameter with a minimization technique to yield neat
      bimodal distributions in a temperature range within the supercooled liquid
      regime, thus clearly revealing the presence of two populations of differently
      structured water molecules. Furthermore, we elucidate the role of the inter
      conversion between the identified two kinds of states for the dynamics of
      structural relaxation, thus linking structural information to dynamics, a long
      standing issue in glassy physics.

PMID- 19603210
TI  - Microwave propagation parameters in magnetic fluids.
AB  - Complex dielectric permittivity and complex magnetic permeability measurements of
      two magnetic fluids (as microwave propagation media), in the approximate range
      0.2-5 GHz were performed. The two samples consisted of magnetite nanoparticles,
      dispersed in kerosene and in water, respectively. Based on the dielectric and
      magnetic measurements, the frequency (f ) dependence of the attenuation
      parameter, [Formula: see text], the phase constant, [Formula: see text], the
      propagation constant, [Formula: see text], the intrinsic impedance, Z(m), the
      refractive index, n, the reflection coefficient, R, the wavelength, [Formula: see
      text] and the skin depth, [Formula: see text], of the investigated samples were
      determined.

PMID- 19603211
TI  - The impact of missing data in the estimation of concentration index: a potential
      source of bias.
AB  - The purpose of this paper is to raise awareness of missing data when
      concentration indices are used to evaluate health-related inequality.
      Concentration indices are most commonly calculated using individual-level survey
      data. Incomplete data is a pervasive problem faced by most applied researchers
      who use survey data. The default analysis method in most statistical software
      packages is complete-case analysis. This excludes any cases where any variables
      are missing. If the missing variables in question are not completely random, the
      calculated concentration indices are likely to be biased, which may lead to
      inappropriate policy recommendations. In this paper, I use both a case study and
      a simulation study to show how complete-case analysis may lead to biases in the
      estimation of concentration indices. A possible solution to correct such biases
      is proposed.

PMID- 19603212
TI  - Factors affecting the production of L-xylulose by resting cells of recombinant
      Escherichia coli.
AB  - Factors affecting the production of the rare sugar L-xylulose from xylitol using
      resting cells were investigated. An E. coli BPT228 strain that recombinantly
      expresses a gene for xylitol dehydrogenase was used in the experiments. The ratio
      of xylitol to L-xylulose was three times lower in the cytoplasm than in the
      medium. The effects of pH, temperature, shaking speed, and initial xylitol
      concentration on L-xylulose production were investigated in shaking flasks using
      statistical experimental design methods. The highest production rates were found
      at high shaking speed and at high temperature (over 44 degrees C). The optimal pH
      for both productivity and conversion was between 7.5 and 8.0, and the optimal
      xylitol concentration was in the range 250-350 g l(-1). A specific productivity
      of 1.09 +/- 0.10 g g(-1) h(-1) was achieved in a bioreactor. The response surface
      model based on the data from the shake flask experiments predicted the operation
      of the process in a bioreactor with reasonable accuracy.

PMID- 19603213
TI  - Enhanced D-ribose biosynthesis in batch culture of a transketolase-deficient
      Bacillus subtilis strain by citrate.
AB  - In this study, the effects of citrate addition on D-ribose production were
      investigated in batch culture of a transketolase-deficient strain, Bacillus
      subtilis EC2, in shake flasks and bioreactors. Batch cultures in shake flasks and
      a 5-l reactor indicated that supplementation with 0.2-0.5 g l(-1) of citrate
      enhanced D: -ribose production. When B. subtilis EC2 was cultivated in a 15-l
      reactor in a complex medium, the D: -ribose concentration was 70.9 g l(-1) with a
      ribose yield of 0.497 mol mol(-1). When this strain was grown in the same medium
      supplemented with 0.3 g l(-1) of citrate, 83.4 g l(-1) of D-ribose were obtained,
      and the ribose yield was increased to 0.587 mol mol(-1). Addition of citrate
      reduced the activities of pyruvate kinase and phosphofructokinase, while it
      increased those of glucose-6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase. Metabolic flux distribution in the stationary phase indicated that
      citrate addition resulted in increased fluxes in the pentose phosphate pathway
      and TCA cycle, and decreased fluxes in the glycolysis and acetate pathways.

PMID- 19603214
TI  - Early to bed, early to rise! Sleep habits and academic performance in college
      students.
AB  - PURPOSE: Prior studies have placed emphasis on the need for adequate total sleep
      time for student performance. We sought to investigate the relative importance of
      total sleep time compared to the timing of sleep and wakefulness for academic
      performance. METHODS: We performed a questionnaire-based survey of college
      students in October 2007. The questionnaire gathered detailed information on
      sleep habits including naps, reasons for missing sleep, academic performance,
      study habits, time spent working outside of school, and stimulant use. RESULTS:
      Compared to those with the lowest academic performance, students with the highest
      performance had significantly earlier bedtimes (p = 0.05) and wake times (p =
      0.008). Napping tended to be more common among high performers (p = 0.07). Of
      importance, there were no significant differences in total sleep time with or
      without naps, weekend sleep habits, study time, gender, race, reasons for staying
      up at night, nor in use of caffeinated beverages, over-the-counter stimulant
      pills, or use of prescription stimulants. CONCLUSIONS: Timing of sleep and
      wakefulness correlated more closely with academic performance than total sleep
      time and other relevant factors. These findings have important implications for
      programs intended to improve academic performance by targeting sleep habits of
      students.

PMID- 19603215
TI  - Effects of allopurinol on cardiac function and oxidant stress in chronic
      intermittent hypoxia.
AB  - RATIONALE: Obstructive sleep apnea is associated with left ventricular (LV)
      dysfunction, oxidant stress, and chronic intermittent hypoxia (CIH). Allopurinol
      (ALLO) is a xanthine oxidase inhibitor that also scavenges free radicals.
      OBJECTIVES: Using an animal model of CIH we hypothesized that ALLO decreases
      oxidant stress and cardiac injury. MATERIALS AND METHODS: Rats were exposed to
      either CIH (nadir 4-6%, approximately once per minute) or room air (handled
      controls, HC) for 8 h a day for 10 days. Four treatment groups (six to ten
      animals per group) were studied: CIH/ALLO, CIH/placebo (PLAC), HC/ALLO, and
      HC/PLAC. Outcomes included myocardial lipid peroxides (LPO) for oxidant stress,
      fraction shortening of the LV cavity for cardiac function (LVFS) and an assay for
      myocyte apoptosis. RESULTS: LPO was lower in CIH/ALLO group compared to CIH/PLAC
      (179 +/- 102 vs. 589 +/- 68 mcg/mg protein, p < 0.05). LVFS was greater in ALLO
      animals than PLAC in both CIH and HC (CIH/ALLO 48.6 +/- 2.3% vs. CIH/PLAC 38 +/-
      1.4%; HC/ALLO 64.9 +/- 1.8% vs. HC/PLAC 51.5 +/- 1.5%; both p < 0.05). Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed fewer
      apoptotic nuclei in LV myocardium in CIH/ALLO compared to CIH/PLAC (38.0 +/- 1.4
      vs. 48.6 +/- 2.3 positive nuclei per 2.5 mm(2) area, p < 0.05). CONCLUSION: ALLO
      is associated with improvement in CIH-associated oxidant stress, myocardial
      dysfunction, and apoptosis in rats.

PMID- 19603217
TI  - [The war on (too many) fluids. New horizons in combat medicine].
AB  - In the coming years, our approach to the bleeding patient will have to change
      radically. The inevitable knowledge from the wars in Iraq and Afghanistan permits
      the prediction that conventional crystalloids will sooner or later disappear from
      volume replacement therapy. The dogma that fluids must always be given will be
      abandoned, to be replaced by the practice of careful and goal-directed
      resuscitation. In the near future, we would rely on designer fluids and
      sophisticated pharmacological agents to deliver personalized resuscitation based
      upon the specific needs of the individual patient.

PMID- 19603216
TI  - [The pelvic subcutaneous cross-over internal fixator].
AB  - The pelvic subcutaneous cross-over internal fixator is a minimally invasive
      technique for the fixation of instable anterior pelvic ring fractures. A USS-II
      VAS screw is anchored bilaterally in the supra-acetabular region of the os ileum
      by a mini-incision approach. An angled fixation rod is inserted subcutaneously
      and after successful closed reduction attached to the screws forming a locking
      internal fixation. In a retrospective study of the clinical and radiological
      outcomes of 19 patients after an average follow-up of 2.54 years, results were
      excellent and good in 31.6%, moderate in 63.2% and poor in 5.3%. Complications
      were one wound infection, one loosening of the VAS screw and seven temporary
      lesions of the lateral femoral cutaneous nerve. The main benefits are a simple
      surgical technique preventing damage to soft tissue, a low risk of neurovascular
      lesions and the avoidance of pin infections. Moreover patients with multiple
      trauma profit from a shorter time of surgery and greater comfort allowing a prone
      position. The new procedure combines the advantages of internal osteosynthesis
      and a minimally invasive technique, providing early mobilization under full
      weight bearing for instable pelvic fractures.

PMID- 19603218
TI  - [Gone well just one more time].

PMID- 19603219
TI  - Combined lumbar spinal and thoracic high-epidural regional anesthesia as an
      alternative to general anesthesia for high-risk patients undergoing
      gastrointestinal and colorectal surgery.
AB  - OBJECTIVE: A prospective study was undertaken to review the use of combined
      lumbar spinal and thoracic high-epidural regional anesthesia in high-risk
      patients who underwent gastrointestinal/colorectal surgery from 2004 to 2006.
      METHODS: Twelve high-risk patients underwent 13 gastrointestinal/colorectal
      surgical procedures, using a regional anesthetic technique, which consisted of a
      thoracic epidural and lumbar subarachnoid block. All patients were classified as
      high risk based on anesthetic assessment (American Society of Anesthesiologists
      (ASA) score 3 or 4). RESULTS: Six (46.2%) of the patients were men, and the
      overall median age was 86 years. Ten (76.9%) patients presented as emergencies,
      whereas only three (23.1%) patients underwent elective procedures. All patients
      subjectively rated their postoperative pain relief as effective. The 30-day
      mortality was 2 (15.4%); however, both of these patients refused initial
      treatment. Only one (7.7%) patient required delayed ITU admission for respiratory
      support (CPAP). None of the patients required intubation at any stage. There were
      two (15.4%) minor and two (15.4%) major early complications and only one (7.7%)
      delayed complication to date. Median length of stay was 7 days. Two (15.4%)
      patients had delayed discharge dates, for social reasons. DISCUSSION: These
      patients demonstrated early postoperative recovery, with effective analgesia, no
      requirements for intubation, and lower morbidity and mortality rates than similar
      studies of high-risk patients who underwent procedures using general anesthesia.
      Using this technique, patients were managed appropriately in HDU and the surgical
      ward, without affecting their overall length of hospital stay. CONCLUSIONS: This
      study supports the role of regional anesthetic techniques, combined with
      targeted, minimally invasive surgery--particularly for the management of high
      risk patients presenting in the emergency setting.

PMID- 19603220
TI  - A randomized clinical trial of frozen vs. standard nasogastric tube placement.

PMID- 19603221
TI  - Lessons learned from the first 109 laparoscopic cholecystectomies performed in a
      single pediatric surgery center.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is a frequent operation in adults
      but is seldom performed in children. A retrospective review of 109 consecutive
      patients who underwent LC over an 11-year period was performed to see what
      lessons were learned from this experience. METHODS: From January 1996 to January
      2007, a total of 109 patients were referred to our unit to undergo LC. Nine adult
      patients were excluded from the analysis. The remaining 100 pediatric patients
      form the basis of this report. Isolated cholecystectomies were performed using a
      four-trocar technique, with a fifth trocar added for cases in which splenectomy
      was required. One patient with main bile duct dilatation at preoperative
      echography underwent peroperative cholangiography. RESULTS: We recorded three
      anatomic anomalies (3%), two involving the bile duct and one the cystic artery.
      We recorded four minor problems during surgery: In one case there was failure of
      the tip of reusable scissors, and in three cases there was a small perforation of
      the gallbladder during the dissection step. We recorded four (4%) postoperative
      complications, which required redo surgery: one patient with bleeding from the
      cystic artery; one case of dislocation of clips positioned on the cystic duct;
      and two patients with lesions of the main bile duct that had not been detected
      during surgery. The treatment consisted in choledojejunostomy on postoperative
      day 7 in one case and suture of the choledocus on a stent positioned using
      endoscopic retrograde cholangiopancreatography on postoperative day 5 in the
      second case. Both biliary complications occurred in patients more than 14 years
      of age. We also recorded one umbilical granuloma. CONCLUSIONS: LC is an effective
      procedure in children. On the basis of our experience, it seems that major
      complications can occur even with experienced surgeons, and they are more
      frequent in teenagers. Biliary or vascular anomalies of the gallbladder are
      encountered in about 3% of patients.

PMID- 19603222
TI  - Vascular and biliary anatomy of the right hilar window: its impact on recipient
      morbidity and mortality for right graft live donor liver transplantation.
AB  - BACKGROUND: Intrahepatic anatomic variations have been associated with both
      morbidity and mortality associated with live donor liver transplantation. The aim
      of our study was to evaluate central hilar and peripheral segmental
      vascular/biliary anatomy in right graft living donor liver transplantation.
      METHODS: From January 2003 to August 2007, three-dimensional (3D) computed
      tomography (CT) reconstructions and virtual 3D hepatectomies were performed in 71
      consecutive right graft live liver donors. A combined two-level classification
      system addressing the four possible combinations of normal (N) and abnormal (A)
      central hilar and peripheral features based on both the existing classification
      and our own classification for portal (portal vein, PV), arterial (hepatic
      artery, HA) and biliary (bile duct, BD) systems was defined as follows: type I,
      N/N; type II, N/A; type III, A/N; and type IV, A/A. RESULTS: A simultaneous
      normal central hilar and peripheral segmental (N/N) anatomy for each system (PV,
      HA, BD) was found in <50% of grafts. The highest incidence of complex vascular
      and biliary reconstructions was observed with grafts having abnormal central
      (type III) or combined abnormal central/peripheral (type IV) anatomy. Central
      hilar arterial and biliary anomalies were predictors of morbidity by both
      univariable and multivariable analyses. CONCLUSIONS: Our two-level classification
      and 3D imaging techniques allowed a cautious surgical approach in high-risk
      cases. Central hilar anatomic variants of the arterial and biliary systems were
      associated with increased morbidity. Further randomized trials will help
      determine the precise extent of our observations.

PMID- 19603225
TI  - Surgical education in Mexico.
AB  - Surgical education in Mexico basically follows the same model as in the United
      States, with a selection process resembling the matching program. There is a 4
      year training period during which residents in their third year spend 4 months as
      the sole surgeon in a rural community. During the senior year they are entitled
      to an elective period in a place of their choosing. After completion of the 4
      years, residents have to present a thesis and undergo an oral examination before
      getting a university diploma. They are then encouraged to pass the written and
      oral examination of the Mexican Board of Surgery before they are fully certified
      to enter practice in a public or private hospital.

PMID- 19603223
TI  - Do we follow evidence-based medicine recommendations during inguinal hernia
      surgery? Results of a survey covering 2441 hernia repairs in 2007.
AB  - BACKGROUND: We conducted a survey to determine whether hernia surgeons follow
      evidence-based medicine (EBM) criteria in their daily routine. METHODS: All
      chiefs of general surgery in Styria (Austria) received a short, simple, two-page,
      10-item questionnaire. RESULTS: We analyzed completed surveys from 15 departments
      reporting 2441 hernia repairs with a mean patient age of 57.5 +/- 11.6 years.
      Although five techniques accounted for 96.6% of procedures, the frequency of use
      of each technique varied considerably among the hospitals. There were high
      numbers of laparoscopic (36.8%) and sutured (19.9%) repairs. CONCLUSIONS: Because
      of the great variance among the evaluated hospitals as to surgical methods and
      indications, this survey showed that inguinal hernia surgery does not currently
      comply with EBM.

PMID- 19603224
TI  - Factors related to preoperative assessment of the circumferential resection
      margin and the extent of mesorectal invasion by magnetic resonance imaging in
      rectal cancer: a prospective comparison study.
AB  - BACKGROUND: This study was designed to identify factors related to inaccurate
      prediction of circumferential resection margin (CRM) and the extent of mesorectal
      invasion (EMI) in T3 tumors by preoperative magnetic resonance imaging (MRI) in
      rectal cancer. METHODS: A total of 66 patients with rectal cancer were enrolled
      prospectively in this study. CRM was defined as the distance from the outer tumor
      margin to the mesorectal fascia, and EMI was defined as the distance from the
      outer surface of the muscularis propria to the outermost tumor margin. CRM and
      EMI measurements on MRI were compared with corresponding measurements from whole
      mount sections using 1-mm and 5-mm reference values, respectively, as prognostic
      indicators. The following variables were analyzed for relevance to preoperative
      staging: tumor distance from the anal verge (lower and middle), tumor location
      (anterior and posterior), tumor (T) and nodal (N) stage, and the thickness of the
      perirectal fat (anterior, left, right, and posterior positions). RESULTS: MRI
      correctly predicted CRM status in 57 of the 66 tumors and EMI status in 51 of the
      58 tumors (eight T1 tumors were excluded from EMI analysis). Univariate analysis
      showed that T3 stage, lymph node involvement, anterior tumor location, and thin
      perirectal fat thickness at the anterior portion were related to incorrect
      prediction of CRM. Anterior tumor location and thin perirectal fat thickness at
      the anterior portion were related to incorrect prediction of EMI. CONCLUSIONS:
      Preoperative chemoradiation can be accurately guided by preoperative MRI staging,
      but CRM and EMI in anterior rectal tumor should be interpreted with caution.

PMID- 19603226
TI  - Early outcome following hepatic resection in patients older than 80 years of age.
AB  - BACKGROUND: We aimed to study the early outcome of patients 80 years of age and
      older undergoing liver resection and to compare the results with the outcomes of
      patients younger than 80 years of age. METHODS: All 350 consecutive patients
      undergoing hepatic resections from 2004 April to 2008 October were included.
      Patients were divided into two groups: 80 years of age and older (group I; n =
      43) and less than 80 years of age (group II; n = 307). Preoperative
      clinicopathological features, intraoperative factors, in-hospital mortality,
      postoperative complications, length of hospital stay, operative mortality,
      morbidity, and prognosis after discharge were analyzed and compared between
      groups I and II. RESULTS: There was no significant difference between the two
      groups regarding the indication for hepatic resection. Hepatitis viral status was
      significantly different between groups: patients without hepatitis B or C viral
      infection were more common in group I than in group II. Regarding preoperative
      liver function, serum levels of albumin were significantly lower in group I than
      in group II. Although the operative time was significantly shorter in group I
      than in group II, no difference was found between groups regarding such operative
      factors as type of hepatectomy, blood loss, and rate of blood transfusion. After
      elimination of 16 patients with extrahepatic bile duct resection and
      reconstruction, no difference existed between the two groups in operative time.
      There was no postoperative mortality nor in-hospital mortality in group I; in
      group II one postoperative death (0.3%) and two in-hospital deaths (0.6%) were
      recorded. There was no difference between groups in the incidence of morbidity
      and early prognosis after discharge. CONCLUSIONS: The results indicate that
      hepatic resection for elderly patients over 80 can be safely performed given
      careful patient selection.

PMID- 19603227
TI  - An evaluation of morbidity and mortality in oncologic gastric surgery with the
      application of POSSUM, P-POSSUM, and O-POSSUM.
AB  - OBJECTIVE: Evaluation of surgical results observed in oncologic gastric surgery
      with reference to estimation of risks through POSSUM (Physiological and Operative
      Severity Score for the enUmeration of Mortality and morbidity), P-POSSUM
      (Portsmouth POSSUM), and O-POSSUM (regression model based on the POSSUM and P
      POSSUM, especially designed for gastric and esophagus surgery). METHODS: A
      prospective follow-up of a cohort of 106 consecutive patients, gastrectomized
      because of gastric cancer. The variables studied were: age, sex, technical
      surgery, American Society of Anesthesiologists (ASA) score, the Charlson
      comorbidity index, morbidity, and mortality. RESULTS: From January 2004 to April
      2008, 131 patients were operated on for gastric neoplasia. Of these, 28 patients
      were excluded: 5 because of nonstandard gastrectomy, 17 because of staging
      laparoscopy or unresectable cancer after laparotomy, and 3 because of palliative
      gastroenteroanastomosis; 106 patients were included. We performed 38 total
      gastrectomies, 65 distal gastrectomies, 2 esophagogastrectomies, and 1 proximal
      gastrectomy. The mean age was 68 years (standard deviation (SD) = 12.1; range, 34
      85 years). Associated comorbidity (Charlson) was 5.4 (SD = 2.7; range, 2-16); ASA
      1 at 1.9%; ASA 2 at 36.8%; ASA 3 at 43.4%; and ASA 4 at 17.9%. Expected
      morbidity, according to POSSUM was 46.7%; observed morbidity was 50.5%. Morbidity
      ratio observed/expected was 1.08. Expected mortality, according to POSSUM = 13%,
      according to P-POSSUM = 4.9%, and according to O-POSSUM = 12.1%. Observed
      mortality was 7.8%. Mortality ratio observed/expected according to POSSUM, P
      POSSUM, O-POSSUM was 0.6, 1.6, and 0.6, respectively. Morbidity results were
      within the confidence interval of the POSSUM estimation. Our results show lower
      mortality than the POSSUM and the O-POSSUM estimation (P < 0.001) and higher
      mortality regarding P-POSSUM estimation (P < 0.001). CONCLUSIONS: The control
      systems of risk allow us continuous evaluation of our results and objective
      comparison to other teams. Compared with the POSSUM scoring systems, our series
      showed quality improvement (morbidity and mortality) over time.

PMID- 19603228
TI  - Effects of obesity surgery on type 2 diabetes mellitus Asian patients.
AB  - BACKGROUND: Obesity is a major risk factor for the development of type 2 diabetes
      mellitus (T2DM). Surgery is the most effective treatment for morbid obesity, and
      it has been shown to lead to dramatic improvement in type T2DM. However, data
      concerning obese Asian patients have not been reported, and the mechanism of
      improving T2DM after bariatric surgery in this population remains speculative.
      METHODS: From April 1997 to March 2006, 1,375 patients undergoing obesity surgery
      were recruited for our study of the effects of weight loss surgery on type 2
      diabetes mellitus (T2DM). Laparoscopic vertical banded gastric partition (LVBG)
      was performed in 552 patients (40.1%), laparoscopic gastric bypass in 660
      patients (48.0%), and laparoscopic adjustable gastric banding (LAGB) in 140
      patients (10.2%). Another 23 patients (1.7%) received open or revision surgery.
      We evaluated the clinical data and effect of obesity surgery on T2DM, impaired
      fasting glucose (IFG) and compared the changes with those with normal fasting
      glucose. RESULTS: Among all the patients, 166 (12.1%) had impaired fasting
      glucose (IFG) and 247 (18.0%) had T2DM. Patients with IFG or DM were
      significantly older, more central obese, and they had higher insulin resistance
      and a higher HbA1C level than those with normal fasting glucose. The mean total
      weight loss for the population was 28.6%, 29.1%, 28.5%, 23.8%, and 24.4% (at 1,
      2, 3, 5, and 7 years after surgery). There was no increase of surgical risk in
      T2DM or IFG patients. One year after operation, fasting plasma glucose returned
      to normal in 78.5% of T2DM patients and 94.7% of IFG patients. The HbA1C level
      returned to under 7.0 in 81.5% of T2DM and in 100% of IFG patients. Laparoscopic
      gastric bypass patients had a greater weight loss and a higher rate of glucose
      normalization (93.1%) than the LVBG patients (85.3%) and LAGB patients (73.9%),
      but no difference in HbA1C normalization. CONCLUSIONS: Obesity surgery resulted
      in significant and sustained weight loss with a cure rate of T2DM up to 80% in
      morbidly obese Asian patients. Gastric bypass surgery had a better result in T2DM
      cure rate than LVBG and LAGB because of better weight reduction.

PMID- 19603229
TI  - Healing of stoma orifices: multicenter, prospective, randomized study comparing
      calcium alginate mesh and polyvidone iodine mesh.
AB  - BACKGROUND: The aim of this multicenter, randomized, prospective study was to
      reveal a difference in terms of a guided healing period in the case of stoma
      orifices after reestablishing digestive continuity by comparing an alginate mesh
      with a polyvidone iodine mesh. METHODS: Between April 2004 and September 2005, a
      total of 73 patients were randomized into two groups: A (alginate mesh) and M
      (polyvidone iodine mesh). The groups were comparable for demographic data,
      indications for and the type of stoma, and perioperative data. The main
      evaluation criterion was percentage healing at the 28th postoperative day (D28);
      and the secondary criteria were healing time, rate of infectious complications,
      and number of dressing changes applied. RESULTS: The mean percentage healing at
      D28 was 91% in group A and 87% in group M (p = 0.49). The mean healing time was
      31 days in group A and 32 days in group M (p = 0.80). One parietal abscess (3%)
      occurred in group A (p = 0.37). The mean number of meshes used was 13 +/- 5 in
      group A and 18 +/- 8 in group M (p < 0.005). CONCLUSION: The use of an alginate
      mesh for guided healing of stoma orifices after reestablishing digestive
      continuity allows effective healing within a normal period of time with a lower
      number of meshes.

PMID- 19603231
TI  - User interface of a teleradiology system for the MR assessment of multiple
      sclerosis.
AB  - The aim of this study was to assess the image display of a web-based
      teleradiology system that uses a common web browser and has no need of
      proprietary applets, plug-ins, or dedicated software for DICOM display. The
      teleradiology system (TS) is connected to the Internet by ADSL and to
      radiological modalities using the DICOM standard with TCP/IP. Images were
      displayed on a PC through Internet connection with the remote TS using a common
      web browser. MS lesion number and volume in T1- and T2-weighted images (T1w and
      T2w, respectively) of 30 brain MR studies were quantified using both the TS and a
      conventional software. Wilcoxon signed ranks test and intraclass correlation
      coefficient (ICC) were used to assess the variability and concordance between
      intra- and inter-observer and TS and conventional DICOM viewer, setting
      significance at p < 0.05. No significant differences in T1w and T2w volumes
      between the TS and the conventional software were found by either operator. The
      ICC results showed a high level of inter-operator agreement in volume estimation
      in T1w and T2w images using the two systems. Quantitative assessment of MS lesion
      volumes in T1w and T2w images with a user interface of a teleradiology system
      that allows the consultation by means of a common web browser, without the need
      for proprietary plug-ins, applets, or dedicated software for DICOM display showed
      no significant differences from, and almost complete agreement with, conventional
      DICOM viewers.

PMID- 19603230
TI  - Evidence for the formation of the male gynogenetic fish.
AB  - The females and unexpected males of gynogenetic red crucian carps (GRCC) with the
      1:1 sex ratio were found in the progeny of the distant crossing of red crucian
      carp (RCC; female symbol, 2n = 100) x blunt snout bream (BSB; male symbol, 2n =
      48). The females and males of GRCC were fertile, and they mated each other to
      generate the red crucian carps (GRCC(1)) and another variational gray crucian
      carps (GGCC). The GRCC and their offspring were proved to be diploids (2n = 100)
      with one to three microchromosomes by examining the chromosomal metaphases. The
      evidences for the male's genetic effect in GRCC were provided by means of
      fluorescence in situ hybridization, Sox-HMG DNA markers, and microsatellite DNA
      markers. The genotypic variances of GRCC resulted in their phenotypic variances
      which were quite different from their maternal parent. It was concluded that the
      formation of the male gynogenetic fish in GRCC resulted from the genetic leakage
      of the paternal fish in the form of the microchromosomes including the paternal
      male-determining gene. After being activated by the sperm of BSB, which was
      inactivated and finally degraded but left the microchromosomes, the egg of RCC,
      in which the 50 chromosomes were spontaneously doubled to 100 chromosomes,
      developed into the diploid male gynogenetic fish. The formation of the bisexual
      GRCC and their progeny indicated that the distant hybridization could generate
      the bisexual diploid gynogenetic fish with genetic variation derived from the
      paternal fish, which is of great significance in both fish genetic breeding and
      evolutionary biology.

PMID- 19603232
TI  - A multicenter observer performance study of 3D JPEG2000 compression of thin-slice
      CT.
AB  - The goal of this study was to determine the compression level at which 3D
      JPEG2000 compression of thin-slice CTs of the chest and abdomen-pelvis becomes
      visually perceptible. A secondary goal was to determine if residents in training
      and non-physicians are substantially different from experienced radiologists in
      their perception of compression-related changes. This study used multidetector
      computed tomography 3D datasets with 0.625-1-mm thickness slices of standard
      chest, abdomen, or pelvis, clipped to 12 bits. The Kakadu v5.2 JPEG2000
      compression algorithm was used to compress and decompress the 80 examinations
      creating four sets of images: lossless, 1.5 bpp (8:1), 1 bpp (12:1), and 0.75 bpp
      (16:1). Two randomly selected slices from each examination were shown to
      observers using a flicker mode paradigm in which observers rapidly toggled
      between two images, the original and a compressed version, with the task of
      deciding whether differences between them could be detected. Six staff
      radiologists, four residents, and six PhDs experienced in medical imaging (from
      three institutions) served as observers. Overall, 77.46% of observers detected
      differences at 8:1, 94.75% at 12:1, and 98.59% at 16:1 compression levels. Across
      all compression levels, the staff radiologists noted differences 64.70% of the
      time, the resident's detected differences 71.91% of the time, and the PhDs
      detected differences 69.95% of the time. Even mild compression is perceptible
      with current technology. The ability to detect differences does not equate to
      diagnostic differences, although perception of compression artifacts could affect
      diagnostic decision making and diagnostic workflow.

PMID- 19603233
TI  - Magnetic resonance imaging in the planning of initial lumpectomy for invasive
      breast carcinoma: its effect on ipsilateral breast tumor recurrence after breast
      conservation therapy.
AB  - BACKGROUND: It remains uncertain whether routine preoperative breast magnetic
      resonance imaging (MRI) will lead to improved local outcomes after breast
      conserving surgery (BCS) and radiation (RT) for invasive carcinoma. The purpose
      of this study was to determine whether MRI in the planning of the first
      lumpectomy reduces ipsilateral breast tumor recurrence (IBTR). METHODS: Using a
      prospective database, 472 initial lumpectomies from 463 women between 1999 and
      2005 were examined. All patients had invasive cancer excised to negative margins
      on BCS, received RT, and were followed. IBTR rates were calculated by Kaplan
      Meier method. Univariate and multivariate analyses were performed to investigate
      the association between MRI for initial lumpectomies and IBTR outcomes. RESULTS:
      MRI was performed before 127 (27%) lumpectomies, while 345 (73%) patients did not
      have a preoperative breast MRI. At median follow-up of 54 months (range 4.8-111.6
      months), there was no significant difference in actuarial 8-year IBTR rates
      between women with preoperative MRI evaluation and women without MRI (1.8% versus
      2.5%, respectively; P=0.67). After adjusting for adjuvant therapies, patient, and
      tumor characteristics, there continued to be no increased risk of IBTR [hazard
      ratio (HR) 1.7; P=0.60]. MRI visualization of tumors prior to lumpectomy did not
      influence the achievement of negative margins and was not associated with lower
      rates of re-excision (MRI: 11.8% versus no-MRI: 13.3%; P=0.50). CONCLUSION: MRI
      evaluation of invasive carcinoma in the planning of initial lumpectomies was not
      associated with improved local outcomes after BCS with RT in this cohort of
      patients.

PMID- 19603234
TI  - Portal vein embolization prior to extensive resection for colorectal liver
      metastases.

PMID- 19603235
TI  - Biological factors, tumor growth kinetics, and survival after metastasectomy for
      pulmonary melanoma.
AB  - INTRODUCTION: Approximately 23% of melanoma patients will eventually develop
      pulmonary metastases and have a median survival of only about 7-11 months.
      Because pulmonary metastasectomy can improve this statistic, we investigated
      clinicopathologic features and biological correlates that might be used to
      identify surgical candidates. METHODS: Archived operative specimens and clinical
      records were retrieved for 20 melanoma patients who underwent resection of
      isolated pulmonary metastases at the John Wayne Cancer Institute, Saint John's
      Health Center. Five-year postmetastasectomy survival (PMS) rate was correlated
      with age, number of pulmonary metastases, tumor doubling time (TDT), tumor
      necrosis, and immunohistochemical expressions of four biological markers: Ki-67,
      glucose transporter-1 (Glut-1), caspase-3, and CD31. RESULTS: Median TDT was 61
      days. On multivariate analysis, TDT (P = 0.008), Glut-1 intensity (P = 0.04), and
      CD31 expression (P = 0.004) were the significant predictors of PMS. Age, number
      of pulmonary metastases, tumor necrosis, and expression of Ki-67 or caspase-3 did
      not significantly impact survival. Median TDT was 56 days with Glut-1 expression
      versus 165 days without Glut-1 expression (P = 0.002), and Glut-1 staining
      intensity independently affected TDT (P = 0.012). CONCLUSIONS: Surgical resection
      may be preferable to toxic systemic therapies in melanoma patients whose isolated
      pulmonary metastases have a long TDT (> or = 61 days) and no biopsy evidence of
      Glut-1 expression.

PMID- 19603237
TI  - Demographic and Financial Analysis of EMTALA Hand Patient Transfers.
AB  - In the United States, the Emergency Medical Treatment and Active Labor Act
      (EMTALA) effectively requires Level I trauma centers to accept hand trauma
      transfers for higher level of care if capacity exists. However, patient transfer
      for non-medical reasons, such as ability to pay, is still perceived as a common
      practice. We hypothesized that EMTALA would cause selective transfer of hand
      patients who were underinsured or uninsured, thus, effectively burdening a Level
      I trauma center. A dedicated transfer center documented the demographics and
      outcomes of all calls for hand trauma transfers from December 2003 to September
      2005. This data registry was reviewed for age, gender, race, insurance status,
      and length of hospital stay. This data was compared with direct admissions to the
      emergency room for hand emergencies during that same time period. During the 2
      year time period, a total of 151 calls for EMTALA transfer were received for hand
      emergencies. Our institution accepted 92 of these patients for transfer. Reasons
      for not accepting transfer included lack of bed availability and unavailability
      of the on-call surgeon due to other emergency operative cases. Compared with hand
      emergency patients brought directly to our emergency department during the same
      time period, transferred patients were younger and had a shorter length of stay.
      Interestingly, they were very similar in terms of sex, race, and insurance
      status. These data suggest that the primary motivations for EMTALA hand trauma
      transfers are truly complexity of patient care and specialist availability. Given
      the often urgent nature of hand trauma surgery and the limited resources
      available, expansion and development of hand and microsurgery regional centers
      will be vital to adequately meet demand without overburdening existing centers.

PMID- 19603238
TI  - Pedicled thoracoabdominal flap coverage about the elbow in traumatic war
      injuries.
AB  - Current military conflicts in Iraq and Afghanistan have produced a significant
      number of complex injury patterns. Multiple extremity trauma and wide zones of
      injury mandate a flexible approach to these problems. We report our experience
      with periarticular elbow injuries with large soft tissue defects. Acute vascular
      reconstruction and multiple wound debridements throughout the evacuation chain
      set the stage for successful rigid fixation. The judicious use of pedicled
      thoracoabdominal flaps remains a viable solution when microvascular techniques
      are less appropriate.

PMID- 19603236
TI  - Prognostic significance of vascular endothelial growth factor in squamous cell
      carcinomas of the tonsil in relation to human papillomavirus status and epidermal
      growth factor receptor.
AB  - BACKGROUND: Angiogenesis markers, vascular endothelial growth factor (VEGF) and
      microvessel density (MVD) have been associated with prognosis in squamous cell
      carcinomas (SCCs) of the head and neck. Other prognostic variables such as human
      papillomavirus (HPV) and epidermal growth factor (EGFR) may also be involved in
      tumour angiogenesis. This study determined relationships between VEGF, MVD, EGFR,
      HPV, response to radiotherapy and clinical outcome in 85 tonsillar SCCs. METHODS:
      HPV status was determined by an HPV multiplex real-time polymerase chain reaction
      (PCR) assay/p16 immunohistochemistry. Expression of VEGF, CD31 (as marker of MVD)
      and EGFR was assessed by semiquantitative immunohistochemistry. RESULTS: Strong
      VEGF expressers were significantly more likely to have higher MVD than were weak
      expressers. There were no associations between VEGF or MVD and gender, patient
      age, TNM stage, EGFR expression or HPV status. Tumours with MVD of >15 per high
      power field were significantly more likely to be poorly differentiated. There was
      a significant inverse relationship between EGFR and HPV status. HPV was a strong
      independent marker of loco-regional recurrence and death. VEGF and EGFR were risk
      factors for local recurrence and disease-specific death on univariate analysis
      but the associations weakened after adjustment for HPV. Among patients treated
      with radiotherapy, VEGF was associated with disease-specific death after
      adjusting for HPV and TMN stage. High-VEGF-expressing tumours positive for EGFR
      had a worse prognosis than all other groups combined after adjusting for HPV and
      TNM stage. CONCLUSIONS: HPV is a stronger prognostic marker than VEGF or EGFR in
      tonsillar SCCs. VEGF correlates with MVD in these tumours.

PMID- 19603240
TI  - Improved esophageal patency when inserting the ProSeal laryngeal mask airway with
      an Eschmann tracheal tube introducer.
AB  - PURPOSE: We hypothesized that a more accurate alignment of the tip of the drain
      tube with the upper esophageal opening would be achieved in adult patients, as
      confirmed by fibreoptic bronchoscopy, by placing the ProSeal laryngeal mask
      airway (PLMA) by means of guiding it over an Eschmann tracheal tube introducer,
      commonly know as a gum elastic bougie (GEB), that was previously inserted into
      the esophagus, rather than by placing the PLMA with a curved metal introducer
      (IT). METHODS: Seventy-five adult elective surgery patients, whose airway
      management involved a PLMA, were randomly allocated to either the GEB- or IT
      guided techniques. After inserting the PLMA, alignment of the tip of the drain
      tube relative to the esophageal opening was verified by a fibrescope introduced
      through the drain tube. Placing the fibrescope through the PLMA identified the
      glottic structures. The primary endpoint indicating the proper alignment of the
      tip of the drain tube of the PLMA with the upper esophageal opening was the
      ability to pass the fibrescope into the esophagus through the drain tube by a
      distance >35 cm without obstruction and the ability to simultaneously visualize
      the esophageal mucosa. RESULTS: The overall success rates of PLMA insertion were
      similar in the GEB and IT groups. However, the mean airway insertion times were
      longer with the GEB than with the IT-PLMA. The GEB group achieved proper
      alignment of the drain tube and the upper esophageal opening more frequently than
      the IT group (97% confidence interval (CI(95)) 91.5-100% vs 81% CI(95) 68.5-93.5%
      of subjects, respectively; P = 0.027). When the GEB was used to place the PLMA,
      the patients' vocal cords were visualized more frequently than when the IT
      technique was used (100% vs 73% CI(95) 58.9-87.1% of subjects, respectively; P =
      0.003). CONCLUSION: Fibreoptic bronchoscopy confirmed that GEB is superior to the
      IT technique in ensuring precise alignment of the tip of the drain tube of the
      PLMA with the upper esophageal opening. Accurate positioning may better preserve
      gastroesophageal drainage function of the PLMA.

PMID- 19603239
TI  - The association of patient age with cardiovascular disease risk factor treatment
      and control in diabetes.
AB  - BACKGROUND: While inadequate treatment intensification may contribute to sub
      optimal CVD risk factor control in older patients with diabetes, the relationship
      between patient age and treatment intensification is largely unexplored.
      OBJECTIVE: To examine differences in treatment intensification and control for
      blood pressure (BP), lipids and A1c in older vs. younger adults with diabetes.
      METHODS: A total of 161,697 Kaiser Permanente Northern California adult diabetes
      patients were stratified by age (<50, 50-64, 65-74 and 75-85) and assessed for
      control of A1c (<8%), LDL-c (<100 mg/dl) and SBP (<140 mmHg). Probit models
      assessed the marginal effects of patient age on treatment intensification and
      control for all three CVD risk factors. RESULTS: Patients aged 50-64 and 65-74
      were significantly more likely to receive treatment intensification for elevated
      SBP than patients under 50 (74% and 76% vs. 71%) and significantly less likely to
      receive treatment intensification for elevated A1c (73% and 72% vs. 76%), with no
      differences noted for LDL-c treatment. Older patients had significantly worse SBP
      control, but better control of A1c and LDL-c. CONCLUSIONS: Both treatment
      intensification rates and control of BP, A1c and LDL cholesterol control varied
      somewhat by age, suggesting room for further improvement in treatment
      intensification and control.

PMID- 19603241
TI  - Controlled clinical, polysomnographic and psychometric studies on differences
      between sleep bruxers and controls and acute effects of clonazepam as compared
      with placebo.
AB  - The pathogenesis, pathophysiology, and pharmacotherapy of sleep bruxism (SB) are
      still not fully understood. We investigated symptomatology, objective and
      subjective sleep and awakening quality of middle-aged bruxers compared with
      controls and acute effects of clonazepam 1 mg compared with placebo by
      polysomnography and psychometry. Twenty-one drug-free bruxers spent 3 nights in
      the sleep lab, 21 age- and sex-matched controls 2 nights. Clinically, bruxers
      exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures, polysomnographically
      impaired sleep maintenance, increased movement time, stage shift index, periodic
      leg movements (PLM) and arousals and psychometrically deteriorated subjective
      sleep and awakening quality, evening/morning well-being, drive, mood, drowsiness,
      attention variability, memory, and fine motor activity. As compared with placebo,
      clonazepam significantly decreased the SB index in all patients (mean: -42 +/-
      15%). Sleep efficiency, maintenance, latency, awakenings and nocturnal wake time,
      the stage shift index, S1, PLM, the arousal index, subjective sleep and awakening
      quality, and fine motor activity improved.

PMID- 19603242
TI  - Prevalence of taste disorders in idiopathic and B. burgdorferi-associated facial
      palsy.
AB  - The frequency of taste disorders in idiopathic facial palsy (IFP) and B.
      burgdorferi-associated facial palsy (BFP) was retrospectively assessed in a
      cohort of patients with acute peripheral facial palsy (AFP). A significant
      (>10/microl) CSF pleocytosis was found in 17% of the patients who underwent
      lumbar puncture for AFP. In two centres, 26 patients with BFP were identified by
      CSF and serological criteria. The control group (patients with IFP) consisted of
      59 patients from one of the centres in whom BFP was excluded by CSF examination.
      AFP patients of both centres are routinely questioned about taste disorders
      according to the hospitals' standards. A taste disorder was found in 46% of the
      IFP and 31% of the BFP cases (not significant). About one-third of the BFP
      patients complained of radicular or back pain. We conclude that a history of
      taste disorder is not helpful in distinguishing clinically between BFP and IFP.

PMID- 19603243
TI  - Remote effects of hippocampal damage on default network connectivity in the human
      brain.
AB  - In the healthy human brain the hippocampus is known to work in concert with a
      variety of cortical brain regions. It has recently been linked to the default
      network of the brain, with the precuneus being its core hub. Here we studied the
      remote effects of damage to the hippocampus on functional connectivity patterns
      of the precuneus. From 14 epilepsy patients with selective, unilateral
      hippocampal sclerosis and 8 healthy control subjects, we acquired functional MRI
      data during performance of an object-location memory task. We assessed functional
      connectivity of a functionally defined region in the precuneus, which showed the
      typical properties of the default network: significant task-related deactivation,
      which was reduced in patients compared to control subjects. In control subjects,
      a largely symmetrical pattern of functional coherence to the precuneus emerged,
      including canonical default network areas such as ventral medial prefrontal
      cortex, inferior parietal cortex, and the hippocampi. Assessment of group
      differences within the default network areas revealed reduced connectivity to the
      precuneus in ipsilesional middle temporal gyrus and hippocampus in left
      hippocampal sclerosis patients compared to controls. Furthermore, left
      hippocampal sclerosis patients showed lower connectivity than right hippocampal
      sclerosis patients in left middle temporal gyrus, ventral medial prefrontal
      cortex, and left amygdala. We report remote effects of unilateral hippocampal
      damage on functional connectivity between distant brain regions associated with
      the default network of the human brain. These preliminary results underline the
      impact of circumscribed pathology on functionally connected brain regions.

PMID- 19603244
TI  - Requirements for generic anti-epileptic medicines: a regulatory perspective.

PMID- 19603245
TI  - Detecting dysphagia in inclusion body myositis.
AB  - Dysphagia is an important yet inconsistently recognized symptom of inclusion body
      myositis (IBM). It can be disabling and potentially life-threatening. We studied
      the prevalence and symptom-sign correlation of dysphagia. Fifty-seven IBM
      patients were interviewed using a standard questionnaire for dysphagia and 43 of
      these underwent swallowing videofluoroscopy (VFS). Symptoms of dysphagia were
      present in 37 of 57 patients (65%). Nevertheless, only 17 of these patients (46%)
      had previously and spontaneously complained about swallowing to their physicians.
      Both symptoms of impaired propulsion (IP) (59%) and aspiration-related symptoms
      (52%) were frequently mentioned. Swallowing abnormalities on VFS were present in
      34 of 43 patients (79%) with IP of the bolus in 77% of this group. The reported
      feeling of IP was confirmed by VFS in 92% of these patients. Dysphagia in IBM is
      common but underreported by the vast majority of patients if not specifically
      asked for. In practice, two questions reliably predict the presence of IP on VFS:
      'Does food get stuck in your throat' and 'Do you have to swallow repeatedly in
      order to get rid of food'. These questions are an appropriate means in selecting
      IBM patients for further investigation through VFS and eventual treatment.

PMID- 19603246
TI  - The morphology and lattice structure of bone crystal after strontium treatment in
      goats.
AB  - Strontium (Sr) compounds have become increasingly popular in osteoporosis
      treatment. As a bone seeking element, 98% of Sr deposits in bone and teeth after
      oral ingestion. However, the quality of new bone after Sr deposition is yet to be
      extensively investigated. In this study, eight osteopenic goats were divided into
      two groups: Ca + 40Sr (five goats) and controls (three goats). Controls were fed
      with low calcium feeds. Ca phosphate was supplied at 100 mg/(kg day), and Sr
      phosphate at 40 mg/(kg day) in the Ca + 40Sr group. The newly formed bone at the
      outer cortical area of the femur with Sr deposition was identified from
      tetracycline labels, and the morphology and lattice structure of the crystals in
      these regions were investigated. Results showed that Sr concentrations of bone
      tissue significantly increased 144.37% for Sr administration without significant
      change in Ca concentration, and the ingested Sr mainly deposited in new bone. The
      crystal isolated from new bone exhibited the typical character of biological
      apatite as determined by Fourier transform infrared spectroscopy and selected
      area electron diffraction. Transmission electron microscopy examination showed
      that a crystal with width of 8-10 nm grew along with the (002) lattice and
      aligned with the same direction in both groups. The elemental analysis of
      crystals showed that the ingested Sr deposited mainly in the bone matrix or was
      absorbed on the bone crystal surface, while only a limited amount of Sr replaced
      Ca in apatite crystals. Our findings showed that Sr administration at current
      dosages for prevention and treatment of osteoporosis might not change the bone
      crystal morphology and structure.

PMID- 19603247
TI  - The effect of thiazolidinediones on bone mineral density in Chinese older
      patients with type 2 diabetes.
AB  - The effect of thiazolidinediones (TZDs) on bone mineral density (BMD) and bone
      metabolism in patients with type 2 diabetes is still in debate. Accumulating
      evidence has emerged that long-term administration of TZDs may increase the
      occurrence of osteoporosis, at least in postmenopausal women. Because little
      clinical data has been reported on Chinese people, a retrospective study was
      performed. One-hundred ninety-eight Chinese people, all from our inpatients, were
      selected for a 24-28 month review (26 +/- 0.5 m). Four groups divided according
      to gender and TZD use were designated fTZD, mTZD, f and m. Changes of subjects'
      BMD and bone metabolism markers were noted and analyzed. Compared with group f,
      bone loss from fTZD in this over 24-month review was more significant in lumbar
      spine (L1-L4) (0.1 +/- 0.15 vs. 0.06 +/- 0.11) and right hip (0.09 +/- 0.15 vs.
      0.05 +/- 0.14) (g/cm(3)) (P < 0.05). However, the opposite result was found in
      male patients with less bone loss in group mTZD. Two bone metabolism markers,
      including beta C-terminal telopeptide of type I collagen (beta-CTX) and
      osteocalcin (OC), in this study did not prove valuable in revealing changes among
      groups. We concluded that long-term TZD use may increase the risk of bone loss in
      Chinese postmenopausal patients with type 2 diabetes, which may provide caution
      on drug treatment in clinical practice. Whether TZD can protect male patients
      against BMD loss or not awaits further research.

PMID- 19603248
TI  - A male patient with malignant lymphoma and thyroid papillary carcinoma after
      pediatric renal transplantation.
AB  - A 6-year-old boy received renal transplantation and was treated with
      methylprednisolone, cyclosporine A and mizoribine. He developed Epstein-Barr
      virus-associated malignant lymphoma at 10 years and thyroid papillary carcinoma
      at 20 years of age. Chemotherapy for the malignant lymphoma was done after
      withdrawal of cyclosporine A and mizoribine, and thyroidectomy was performed for
      thyroid carcinoma. He was well and his serum creatinine was 1.0 mg/dl at 22 years
      of age. To our knowledge, no pediatric renal transplant recipient who had thyroid
      carcinoma or two different types of tumor has been reported in Japan.

PMID- 19603251
TI  - Long-term efficacy of leflunomide on disease activity and inhibition of joint
      damage: retrospective comparison with methotrexate for Japanese rheumatoid
      arthritis patients.
AB  - We retrospectively compared treatment impact with leflunomide (LEF) or
      methotrexate (MTX) on retarding joint damage and clinical symptom including a 28
      joint-count Disease Activity Score/erythrocyte sedimentation rate (DAS28-ESR)
      between two similar groups in patients with rheumatoid arthritis (RA) over an
      approximately 3-year treatment. One group included 29 patients treated with LEF
      alone (average dose 16.1 mg/day); the other group included 26 patients treated
      with MTX (average dose 7.4 mg/week) alone or combined with other disease
      modifying antirheumatic drugs. At baseline, mean disease duration was 7.1 and 6.9
      years, and mean DAS28-ESR was 5.79 and 5.69, respectively. The average DAS28-ESR
      improvement of 1.750 (from 5.79 to 4.04) in the LEF-treated group was
      significantly greater than the effect of 1.007 (from 5.69 to 4.68) seen in the
      MTX group (P = 0.0455), with the same results being observed on European League
      Against Rheumatism (EULAR) response criteria. Annual changes observed in Larsen
      score in total joints were 0.030 in the LEF group and 0.085 in the MTX group: LEF
      retards joint damage significantly better than MTX (P = 0.003). This inhibitory
      effect was better in small joints (P = 0.004) than in middle and large joints (P
      = 0.075). A negative correlation was noticed between improved DAS28-ESR and the
      progression of joint damage in the LEF group (r = -0.7068, P < 0.0001), whereas
      there was no correlation in the MTX group (r = -0.0311, P = 0.882). In daily
      clinical practice, LEF showed significant clinical and radiological improvement
      compared with the standard MTX regimen in Japan.

PMID- 19603250
TI  - Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a
      patient with lipoprotein glomerulopathy.
AB  - Lipoprotein glomerulopathy (LPG) is a rare hereditary disease characterized by
      the accumulation of much thrombi material consisting of lipoproteins at the
      glomerular capillary lumen. Most patients show nephrotic syndrome; nearly half
      progress to chronic renal failure. Intensive therapy with lipid-lowering agents
      reportedly engenders clinical remission with histological resolution. We report
      the case of a 14-year-old Japanese female patient who had been in a nephrotic
      condition with hematuria from 4 years old and who had been diagnosed based on
      pathological and molecular examination at 7 years old. We initially treated the
      patient with probucol, enalapril (angiotensin-converting enzyme inhibitor: ACEI),
      and dipyridamole from age 7, but achieved no improvement in her nephrotic status.
      Subsequently, we replaced probucol with bezafibrate at age 11 and added
      atorvastatin calcium hydrate and valsartan (angiotensin II receptor blocker: ARB)
      the following year. The next 3 years' treatment improved her nephrotic status,
      decreased serum apolipoprotein E, and markedly decreased intraglomerular
      lipoprotein thrombi. Early and intensive therapy with antilipidemic drugs
      combined with ACEI and ARB is inferred to be effective for LPG.

PMID- 19603252
TI  - Development and characterization of microsatellite loci in Ixeridium dentatum
      (Asteraceae, Lactuceae).
AB  - We isolated and characterized seven microsatellite loci for the perennial herb
      Ixeridium dentatum ssp. dentatum, an apomictic triploid distributed throughout
      the lowland areas of East Asia. The number of alleles ranged from two to seven in
      32 screened individuals of I. dentatum ssp. dentatum from Japan. The observed and
      expected heterozygosities were 0.000-0.950 and 0.000-0.891, respectively,
      calculated using genotypes of 20 individuals of I. dentatum ssp. nipponicum. One
      locus (msid4) deviated significantly from Hardy-Weinberg equilibrium (P =
      0.0001). These microsatellites were also tested for cross-amplification in 11
      other taxa of Lactuceae, including five endangered taxa. These primers should be
      useful genetic tools not only for Ixeridium but also for other Lactuceae taxa.

PMID- 19603253
TI  - Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone
      glycosides on chemical substance-induced dermatitis in mice.
AB  - Oral administration of a 50% ethanolic extract (CH-ext) obtained from unripe
      Citrus hassaku fruits collected in July exhibited a potent dose-dependent
      inhibition of IgE (immunoglobulin E)-mediated triphasic cutaneous reaction at 1 h
      [immediate phase response (IPR)], 24 h [late phase response (LPR)] and 8 days
      [very late phase response (vLPR)] after dinitrofluorobenzene challenge in mice.
      Naringin, a major flavanone glycoside component of CH-ext, showed a potent dose
      dependent inhibition against IPR, LPR and vLPR. Neohesperidin, another major
      glycoside component of CH-ext, showed an inhibition against vLPR. The effect of
      CH-ext on type IV allergic reaction was examined by determining inhibitory
      activity against ear swelling in mice by using the picryl chloride-induced
      contact dermatitis (PC-CD) model. Oral administration (p.o.) of CH-ext and
      subcutaneous administration (s.c.) of prednisolone inhibited ear swelling during
      the induction phase of PC-CD. The inhibitory activities of combinations of CH-ext
      (p.o.) and prednisolone (s.c.) against PC-CD in mice were more potent than those
      of CH-ext alone and prednisolone alone, without enhancing the adverse effects.
      Other combinations of prednisolone (s.c.) and flavanone glycoside (p.o.)
      components of CH-ext, i.e. naringin and neohesperidin, exerted similar
      synergistic effects.

PMID- 19603254
TI  - Evaluation of subjective symptoms of Japanese patients with multiple chemical
      sensitivity using QEESI(c).
AB  - OBJECTIVES: The Quick Environment Exposure Sensitivity Inventory (QEESI(c)) has
      been used as a questionnaire to evaluate subjective symptoms of patients with
      multiple chemical sensitivity (MCS), also known as idiopathic environmental
      intolerance, in Japan. However, no cutoff value for Japanese subjects has yet
      been established. We designed this study to establish a cutoff value for Japanese
      subjects using QEESI(c) for screening of MCS patients. METHODS: A questionnaire
      using the QEESI(c) was administered to 103 MCS patients and 309 healthy control
      subjects matched for age and sex. QEESI(c) scores of the two groups were compared
      using logistic regression analysis, receiver operating characteristic analysis,
      and the Mann-Whitney test. RESULTS: Cutoff values for Japanese subjects were
      determined for the Chemical Intolerance subscale (40), Symptom Severity subscale
      (20), and Life Impact subscale (10). The subjects whose scores exceeded the
      cutoff values in any two subscales accounted for 88.4% of the patients but only
      14.5% of the controls. CONCLUSIONS: Our results suggest that subjects meeting two
      out of three subscale criteria can be screened as "patients suffering from a low
      level of environmental chemicals such as MCS" in Japan.

PMID- 19603255
TI  - Adenovirus-mediated hypoxia-inducible factor 1alpha double-mutant promotes
      differentiation of bone marrow stem cells to cardiomyocytes.
AB  - The hypoxia-inducible factor 1alpha (HIF-1alpha) regulates transcriptional genes
      involved in cell proliferation, survival, and differentiation. Under normoxia,
      HIF-1alpha has a short half-life (t((1/2)) approximately 5 min) and low
      transcriptional activity. An HIF-1alpha mutant, produced by substitution of
      alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position
      803, can prevent HIF-1alpha hydroxylation and results in a highly active form of
      HIF-1alpha (HIF-1alpha-Ala564-Ala803). We hypothesized that adenovirus (Ad)
      mediated transfer of the active form of HIF-1alpha (pAd-HIF-1alpha-Ala564-Ala803)
      could effectively occur in bone marrow stem cells (MSCs) and promote MSC
      differentiation under normoxia. PCR-based site-specific mutagenesis was used to
      construct the Ad vector expressing HIF-1alpha-Ala564-Ala803. RT-PCR and
      immunostaining were used to study whether pAd-HIF-1alpha-Ala564-Ala803 affected
      MSC differentiation to cardiomyocyte (CMC). pAd-HIF-1alpha-Ala564-Ala803
      exhibited higher transcriptional activity and stable HIF-1alpha protein
      expression. Under normoxia, an MSC-CMC co-culture treated with pAd-HIF1a-Ala564
      Ala803 augmented TGF-beta(1), Smad4, NKx2.5, and GATA4 expression. Higher
      expression of cTnT and alpha-actinin was observed by immunostaining in MSCs,
      compared with the control and contrast groups. Adenovirus-mediated hypoxia
      inducible factor 1alpha double-mutant, pAd-HIF-1alpha-Ala564-Ala803, can stably
      express HIF-1alpha and promote its downstream genes and MSC differentiation to
      CMC in the MSC-CMC co-culture system under normoxia.

PMID- 19603256
TI  - Characterization of the complete genome sequence of pike fry rhabdovirus.
AB  - The complete genome sequence of pike fry rhabdovirus (PFRV), consisting of 11,097
      nucleotides, was determined. The genome contains five genes, encoding the
      nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and
      RNA-dependent RNA polymerase (L) protein in the order 3'-N-P-M-G-L-5'. 3' leader-
      and 5' trailer-sequences in the PFRV genome show inverse complementarity. The
      PFRV proteins share the highest homology to the proteins of spring viremia of
      carp virus (SVCV), ranging from 55.3 to 91.4%. Phylogenetic analysis of the five
      proteins showed that PFRV clusters with SVCV and is closely related to the
      mammalian vesiculoviruses, 903/87, STRV and SCRV.

PMID- 19603257
TI  - Detection and characterization of soluble CD93 released during inflammation.
AB  - BACKGROUND: CD93 is a cell surface glycoprotein that is required for efficient
      engulfment of apoptotic cells via an unknown mechanism. Recently, it was
      demonstrated that CD93 is proteolytically cleaved from the surface of activated
      human monocytes and neutrophils in response to inflammatory signals in vitro and
      that a soluble form of CD93 (sCD93) exists in human plasma. OBJECTIVE: The
      objective of this study was to examine the relationship among production of
      sCD93, inflammation, and engulfment of apoptotic cells. METHODS: Sterile
      peritonitis was induced in C57BL/6 mice, and lavage fluid was analyzed for
      presence of sCD93 by ELISA and Western blot. Cellular infiltrate was assessed by
      flow cytometry and analyzed for its capacity to shed CD93 in vitro. Peritoneal
      lavage fluid (PLF) was examined for its ability to regulate engulfment of
      apoptotic cells. RESULTS: There was an 8.9-fold increase in sCD93 following
      induction of peritonitis. Macrophages accounted for the majority of infiltrating
      leukocytes into the peritoneum when sCD93 levels were highest. Inflammatory
      peritoneal macrophages constitutively shed CD93 in vitro suggesting that this
      cell type contributes to elevated levels of sCD93 in vivo. Inflammatory PLF from
      wild-type mice containing elevated sCD93 significantly enhanced engulfment of
      apoptotic cells in vitro when compared to inflammatory fluid from CD93-deficient
      mice. CONCLUSIONS: These data demonstrate that inflammation triggers release of
      sCD93 in vivo, identify the inflammatory macrophage as a source of sCD93, and
      provide insight into the mechanism by which CD93 contributes to engulfment of
      apoptotic cells.

PMID- 19603258
TI  - Predicting inhibitors of acetylcholinesterase by regression and classification
      machine learning approaches with combinations of molecular descriptors.
AB  - PURPOSE: Acetylcholinesterase (AChE) is both a therapeutic target for Alzheimer's
      disease and a target for organophosphorus, carbamates and chemical warfare
      agents. Prediction of the likelihood of compounds interacting with this enzyme is
      therefore important from both therapeutic and toxicological perspectives.
      MATERIALS AND METHODS: Support vector machine classification and regression
      models with molecular descriptors derived from Shape Signatures and the Molecular
      Operating Environment (MOE) application software were built and tested using a
      set of piperidine AChE inhibitors (N = 110). RESULTS: The combination of the
      alignment free Shape Signatures and 2D MOE descriptors with the Support Vector
      Regression method outperforms the models based solely on 2D and internal 3D (i3D)
      MOE descriptors, and is comparable with the best previously reported PLS model
      based on CoMFA molecular descriptors (r(2)(test,SVR) = 0.48 vs. r(2)(test,PLS) =
      0.47 from Sutherland et al. J Med Chem 47:5541-5554, 2004). Support Vector
      Classification algorithms proved superior to a classifier based on scores from
      the molecular docking program GOLD, with the overall prediction accuracies being
      Q(SVC(10CV)) = 74% and Q(SVC(LNO)) = 67% vs. Q(GOLD) = 56%. CONCLUSIONS: These
      new machine learning models with combined descriptor schemes may find utility for
      predicting novel AChE inhibitors.

PMID- 19603259
TI  - The NODS-CLiP: a rapid screen for adult pathological and problem gambling.
AB  - OBJECTIVES: To describe and evaluate tests of the performance of the NODS-CLiP,
      an efficient standardized diagnostic interview instrument for adult pathological
      and problem gambling. SETTING AND SAMPLES: Identical batteries of diagnostic
      questions about gambling behavior, motives, and thoughts were administered to
      participants in eight general adult population field studies conducted in the
      United States between 1999 and 2003, including six state-level random-digit-dial
      (RDD) telephone surveys, one national RDD survey, and one in-person systematic
      random sample survey of commercial gambling patrons in eight states. Total survey
      N = 17,180. Response rates ranged from 24 to 71%. MEASURES: Data from all
      experienced gamblers (N = 8,867) were re-analyzed to compare diagnostic status
      derived from the 17-item NORC Diagnostic Screen for Gambling Disorders (NODS), a
      validated DSM-IV-based instrument, with results from all 2- to 4-item subsets of
      NODS items. RESULTS: Three NODS questions pertaining to loss of Control, Lying,
      and Preoccupation (the "CLiP"), requiring one minute to administer, identified
      virtually all pathological gamblers and most problem gamblers diagnosed by the
      complete NODS. The CLiP has excellent sensitivity and specificity for NODS
      constructs. CONCLUSIONS: A two-stage NODS-CLiP procedure appears quite promising
      as an efficient epidemiological instrument for general population research and
      clinical triage for gambling disorders.

PMID- 19603260
TI  - "A study in nature": the Tuskegee experiments and the New South plantation.
AB  - This essay rethinks the Tuskegee Syphilis Experiments in light of a long history
      of experimentation in plantation geographies of the U.S. South. Turning to late
      nineteenth- and early twentieth-century discourses of the New South and to Booker
      T. Washington's Tuskegee Institute, this essay illuminates the extension of the
      laboratory life of the plantation into the twentieth century. The focus on
      personal hygiene at the Tuskegee Institute opened the door for alliances with
      public health initiatives early on, making the school's student population as
      well as residents of surrounding counties subjects of intense hygienic
      surveillance well before the official start of the syphilis study.

PMID- 19603261
TI  - Police-induced confessions: risk factors and recommendations.
AB  - Recent DNA exonerations have shed light on the problem that people sometimes
      confess to crimes they did not commit. Drawing on police practices, laws
      concerning the admissibility of confession evidence, core principles of
      psychology, and forensic studies involving multiple methodologies, this White
      Paper summarizes what is known about police-induced confessions. In this review,
      we identify suspect characteristics (e.g., adolescence; intellectual disability;
      mental illness; and certain personality traits), interrogation tactics (e.g.,
      excessive interrogation time; presentations of false evidence; and minimization),
      and the phenomenology of innocence (e.g., the tendency to waive Miranda rights)
      that influence confessions as well as their effects on judges and juries. This
      article concludes with a strong recommendation for the mandatory electronic
      recording of interrogations and considers other possibilities for the reform of
      interrogation practices and the protection of vulnerable suspect populations.

PMID- 19603262
TI  - Effects of endotoxin and catecholamines on hepatic mitochondrial respiration.
AB  - Catecholamines are frequently used in sepsis, but their interaction with
      mitochondrial function is controversial. We incubated isolated native and
      endotoxin-exposed swine liver mitochondria with either dopamine, dobutamine,
      noradrenaline or placebo for 1 h. Mitochondrial State 3 and 4 respiration and
      their ratio (RCR) were determined for respiratory chain complexes I, II and IV.
      All catecholamines impaired glutamate-dependent RCR (p = 0.046), predominantly in
      native mitochondria. Endotoxin incubation alone induced a decrease in glutamate
      dependent RCR compared to control samples (p = 0.002). We conclude that
      catecholamines and endotoxin impair the efficiency of mitochondrial complex I
      respiration in vitro.

PMID- 19603263
TI  - Closed-system solid surface vitrification versus slow programmable freezing of
      mouse 2-cell embryos.
AB  - PURPOSE: To compare closed-system solid surface vitrification with slow freezing.
      METHODS: Mouse 2-cell embryos (n = 348) were divided into vitrification, slow
      freezing and non-frozen groups. For vitrification, embryos were exposed to 10%
      ethylene glycol (EG), 10% dimethylsulfoxide (DMSO) and 10% fetal bovine serum
      (FBS) in phosphate-buffered saline (PBS) for 10 min, then transferred into 17.5%
      EG, 17.5% DMSO, 0.25 M trehalose and 10% FBS in PBS. They were placed on hemi
      straws and inserted into 0.5 ml straws inside a previously cooled aluminum
      cylinder. Slow freezing was done in straws by the conventional method. RESULTS:
      Vitrified embryos had significantly higher survival, further cleavage and
      blastocyst formation rates than those in the slow freezing group (p < 0.001) and
      were comparable to controls. Blastocysts in the vitrification and control groups
      had significantly more cells than those in the slow freezing group (p < 0.05).
      CONCLUSIONS: Closed-system vitrification was more effective than conventional
      slow freezing.

PMID- 19603264
TI  - Development of microsatellite markers from an enriched genomic library for the
      genetic analysis of the Malaysian giant freshwater prawn, Macrobrachium
      rosenbergii.

PMID- 19603266
TI  - Biomonitoring the environmental impact of atmospheric emissions from the
      Avonmouth zinc smelter, United Kingdom.
AB  - This paper examines the impact of an industrial point-source atmospheric emission
      on the feeding of early life stages of a terrestrial invertebrate. Larvae of a
      bagworm moth, Luffia ferchaultella [Stephens], were fed terrestrial epiphytic
      algae (Desmococcus viridis [Menegh]) collected from five sites located along a 16
      km transect around the Avonmouth zinc smelter. After 10 days of exposure symptoms
      of lethal and sublethal toxicity (mortality and paralysis) were observed.
      Reductions in the amount of faecal material (frass) produced were also
      identified, and these correlated with distance downwind of the smelter. The
      elevated concentrations of lead, mercury, arsenic, antimony, copper, cadmium,
      lead and nickel present in the algae could account for these symptoms of
      toxicity. Similar symptoms were observed when larvae were fed algae spiked with
      inorganic mercury. These results are consistent with other studies of soil
      toxicity conducted around the Avonmouth smelter. However, the current study
      suggests that the impacted area exceeds this 16 km transect and demonstrates the
      value of bagmoth larvae as sensitive biomonitors of metallic atmospheric
      pollutants above the rhizosphere.

PMID- 19603265
TI  - Clinical evaluation of chemotherapy response predictors developed from breast
      cancer cell lines.
AB  - The goal of this study was to develop pharmacogenomic predictors in response to
      standard chemotherapy drugs in breast cancer cell lines and test their predictive
      value in patients who received treatment with the same drugs. Nineteen human
      breast cancer cell lines were tested for sensitivity to paclitaxel (T), 5
      fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) in vitro. Baseline
      gene expression data were obtained for each cell line with Affymetrix U133A gene
      chips, and multigene predictors of sensitivity were derived for each drug
      separately. These predictors were applied individually and in combination to
      human gene expression data generated with the same Affymetrix platform from fine
      needle aspiration specimens of 133 stage I-III breast cancers. Tumor samples were
      obtained at baseline, and each patient received 6 months of preoperative TFAC
      chemotherapy followed by surgery. Cell line-derived prediction results were
      correlated with the observed pathologic response to chemotherapy. Statistically
      robust differentially expressed genes between sensitive and resistant cells could
      only be found for paclitaxel. False discovery rates associated with the
      informative genes were high for all other drugs. For each drug, the top 100
      differentially expressed genes were combined into a drug-specific response
      predictor. When these cell line-based predictors were applied to patient data,
      there was no significant correlation between observed response and predicted
      response either for individual drug predictors or combined predictions. Cell line
      derived predictors of response to four commonly used chemotherapy drugs did not
      predict response accurately in patients.

PMID- 19603267
TI  - Biochemical endpoints on juvenile Solea senegalensis exposed to estuarine
      sediments: the effect of contaminant mixtures on metallothionein and CYP1A
      induction.
AB  - Juvenile Solea senegalensis were exposed to fresh sediments from three stations
      of the Sado estuary (Portugal) in 28-day laboratory assays. Sediments revealed
      distinct levels of total organic matter, fine fraction, redox potential, trace
      elements (arsenic, cadmium, chromium, copper, nickel, lead and zinc) and organic
      contaminants (polycyclic aromatic hydrocarbons, polychlorinated biphenyls and a
      pesticide: dichloro diphenyl trichloroethane). Organisms were surveyed for
      contaminant bioaccumulation and induction of two hepatic biochemical biomarkers:
      metallothionein (MT) and cytochrome P450 (CYP1A), as potential indicators of
      exposure to metallic and organic contaminants, respectively. Using an integrative
      approach it was established that, although bioaccumulation is in general
      accordance with sediment contamination, lethality and biomarker responses are not
      linearly dependent of the cumulative concentrations of sediment contaminants but
      rather of their bioavailability and synergistic effects in organisms. It is
      concluded that metals and organic contaminants modulate both MT and CYP1A
      induction and it is suggested that reactive oxygen species may be the link
      between responses and effects of toxicity.

PMID- 19603268
TI  - Biomarkers of exposure to metal contamination and lipid peroxidation in the
      benthic fish Cathorops spixii from two estuaries in South America, Brazil.
AB  - Biomarkers as lipid peroxidation, metallothionein and delta-aminolevulinic acid
      dehydratase were determined in Cathorops spixii to compare the biological
      responses of this fish from estuaries with distinct anthropogenic influence.
      Three areas were selected in two estuaries in accordance with the levels of
      contamination for the polluted (Santos/Sao Vicente) and with the hydrodynamic
      characteristics for the non-polluted (Cananeia) estuary. Water characteristics
      and mercury levels in C. spixii confirmed a high human influence in the polluted
      system. In general, the biomarkers showed differences between the estuaries,
      suggesting disturbances in the specific cell mechanisms due to the presence of
      multiple xenobiotics in the contaminated system. Therefore, these biomarkers are
      recommended to promote more accurate information about the exposure to
      pollutants. Additionally, the study of the effect of the multiple xenobiotics on
      resident species such as the benthic fish C. spixii can favor a better assessment
      of the environmental quality of these systems.

PMID- 19603269
TI  - Alterations of valve closing behavior in juvenile Catarina scallops (Argopecten
      ventricosus Sowerby, 1842) exposed to toxic metals.
AB  - We conducted an evaluation of alterations produced in the valve closing speed of
      juvenile Argopecten ventricosus (Catarina scallop) exposed to the metals cadmium,
      chromium and lead, because of the connection of this response to the state of
      health of the mollusk. Bioassays were conducted with 50 juveniles (length 3 +/-
      0.5 cm) exposed to 0.02, 0.1, 0.2 mg Cd l(-1); 0.1, 0.5, 1.0 mg Cr l(-1); 0.04,
      0.2, 0.4 mg Pb l(-1) and 0.8 and 1.6 mg Cd + Cr + Pb l(-1) for 480 h. The average
      valve closing speed at the end of the experiment was under 1 s in the control
      group, from 2 to 3.6 s in the bioassays with cadmium, from 1.4 to 3.4 s with
      chromium, from 3 to 12 s with lead, and from 12 to 15 s with the metal mixtures.
      It was found that there are significant differences between the values recorded
      in assays with metals and the control (P < 0.05). The retardation of valve
      closing in the organisms exposed to toxic substances is probably caused by damage
      to the sensory cilia located on the edge of the mantle.

PMID- 19603270
TI  - Continuous and noninvasive blood pressure measurement: a novel modeling
      methodology of the relationship between blood pressure and pulse wave velocity.
AB  - In this paper, we aim to establish a new mathematical model that relates pulse
      wave velocity (PWV) to blood pressure (BP) for continuous and noninvasive BP
      measurement. For the first time, we derive an ordinary differential equation
      (ODE) expressing the fundamental relation between BP, elastic modulus G and PWV.
      The general solution of this ODE is the mathematical BP-PWV model. In our model,
      the elastic modulus G is included in model parameters, unlike the existing
      theoretical models. This enables us to express the BP-PWV relationship for
      subjects of different ages and genders. A family of BP-PWV functions for specific
      age and gender groups can be obtained using statistical methods based on clinical
      trial data, which serve as the calibrated benchmark models for continuous and
      noninvasive BP measurement. To illustrate the modeling methodology, we construct
      benchmark models for people aged 19 and 60 and apply them to continuous diastolic
      blood pressure (DBP) measurement without individual calibration. The results of
      clinical tests meet the test standard in ANSI/AAMI SP10, which attests the
      feasibility of the modeling methodology.

PMID- 19603271
TI  - Measuring the food environment: shelf space of fruits, vegetables, and snack
      foods in stores.
AB  - Dietary patterns may be influenced by the availability and accessibility within
      stores of different types of foods. However, little is known about the amount of
      shelf space used for healthy and unhealthy foods in different types of stores. We
      conducted measurements of the length of shelf space used for fruits, vegetables,
      and snack foods items in 419 stores in 217 urban census tracts in southern
      Louisiana and in Los Angeles County. Although supermarkets offered far more shelf
      space of fruits and vegetables than did other types of stores, they also devoted
      more shelf space to unhealthy snacks (mean 205 m for all of these items combined)
      than to fruits and vegetables (mean 117 m, p < 0.001). After supermarkets, drug
      stores devoted the most shelf space to unhealthy items. The ratio of the total
      shelf space for fruits and vegetables to the total shelf space for these
      unhealthy snack items was the lowest (0.10 or below) and very similar in
      convenience stores, drug stores, and liquor stores, was in a middle range (0.18
      to 0.30) in small food stores, and was highest in medium-sized food stores (0.40
      to 0.61) and supermarkets (0.55 to 0.72). Simple measurements of shelf space can
      be used by researchers to characterize the healthfulness of the food environment
      and by policymakers to establish criteria for favorable policy treatment of
      stores.

PMID- 19603273
TI  - Atrazine degradation by a simple consortium of Klebsiella sp. A1 and Comamonas
      sp. A2 in nitrogen enriched medium.
AB  - A simple consortium consisted of two members of Klebsiella sp. A1 and Comamonas
      sp. A2 was isolated from the sewage of a pesticide mill in China. One member of
      Klebsiella sp. A1 is a novel strain that could use atrazine as the sole carbon
      and nitrogen source. The consortium showed high atrazine-mineralizing efficiency
      and about 83.3% of 5 g l(-1) atrazine could be mineralized after 24 h
      degradation. Contrary to many other reported microorganisms, the consortium was
      insensitive to some nitrogenous fertilizers commonly used, not only in presence
      of 200 mg l(-1) atrazine but also in 5 g l(-1) atrazine mediums. After 24 h
      incubation, 200 mg l(-1) atrazine was completely mineralized despite of the
      presence of urea, (NH(4))(2)CO(3) and (NH(4))(2)HPO(4) in the medium. Very minor
      influence was observed when NH(4)Cl was added as additional nitrogen source.
      Advantages of the simple consortium, high mineralizing efficiency and
      insensitivity to most of exogenous nitrogen sources, all suggested application
      potential of the consortium for the bioremediation of atrazine-contaminated soils
      and waters.

PMID- 19603275
TI  - Monitoring structural assets of bi-species groves according to land use types: a
      case study from arid plains.
AB  - This paper provides a framework for the managers to devise means to protect,
      restore, and maintain the remaining bi-species groves for sustainable management
      of fragile arid land ecosystem. At the moment, there is no information available
      about the structural and functional ecology of these dwindling remnants. The
      selection criteria for the classification of the groves are based on
      understanding the positive association between the two species, Prosopis
      cineraria and Salvadora oleoides, in terms of spatial pattern and morphological
      features. It was achieved by highlighting the attributes of the benchmark grove
      and classification of other groves in reference to it. The results clearly show
      that positive association in the groves is due to differences in the growth
      strategies of the two species in terms of above- and belowground biomass
      allocation and architecture. Most of the groves are in various stages of
      degradation, and anthropogenic interferences are the major determinant linked
      with the declining status of the groves. These activities affect the
      complimentary attributes of the bi-species groves, thus disturbing the
      characteristic structural features which contributed to the stability of this
      fragile landscape.

PMID- 19603274
TI  - Olive mill wastewater disposal in evaporation ponds in Sfax (Tunisia): moisture
      content effect on microbiological and physical chemical parameters.
AB  - The study of the isotherms desorption of olive mill wastewater (OMW) was
      investigated to describe its water activity under different saturated
      environments. The microbial biodegradation of OMW during its storage in 5
      evaporation ponds located in Agareb (Sfax-Tunisia) was carried out during the oil
      harvesting year held 105 days in 2004. Gravimetric static method using saturated
      salt solutions was used and OMW as placed at 30 degrees C and under different
      water activities ranging from 0.11 to 0.90. Eight models were taken from the
      literature to describe experimental desorption isotherms. During storage, the
      evolution of physico-chemical parameters including pH, temperature, evaporation,
      humidity, total phosphorus, chemical oxygen demand (COD), biological oxygen
      demand (BOD) and phenols and three microbiological flora (aerobic mesophilic
      bacteria, yeasts and moulds) were considered. At 30 degrees C, when relative
      humidity increased in the experimented ponds of 69, 84 and 90%, the evaporation
      speed decreased from 1.24 x 10(-5) to 5 x 10(-6) cm(3) s(-1), from 6 x 10(-5) to
      7 x 10(-6) cm(3) s(-1) and from 5 x 10(-6) to 1.1 x 10(-7) cm(3) s(-1)
      respectively. The desorption isotherm exhibited a sigmoidal curve corresponding
      to type II, typical of many organic material. The GAB and Peleg models gave the
      best fit for describing the relationship between the equilibrium moisture content
      and water activity in OMW (R (2) = 0.998). During the storage period, the
      analysis showed an increase of all the physico-chemical parameters studied,
      except phenols and total phosphorus concentrations. The microbiological study
      showed the predominance of yeasts and moulds and the decrease of bacteria
      population after 75 days reflecting both effect of recalcitrant compounds and the
      water activity on microbial growth.

PMID- 19603276
TI  - Alteration in hematology of Labeo rohita under stress of pollution from Lakes of
      Bangalore, Karnataka, India.
AB  - Blood is an indicator of physiological condition of an animal. Therefore, a field
      study was conducted to investigate the hematological parameters of wild
      population of rohu, Labeo rohita (Ham). The following aspects were evaluated in
      blood: hemoglobin content, red blood cell (RBC) and white blood cell (WBC) count,
      packed cell volume (PCV), and mean corpuscular volume (MCV) and mean corpuscular
      hemoglobin concentration (MCHC) values, and in plasma: cholesterol, protein, and
      glucose levels. For this purpose, rohu fish of varying sizes and weights were
      sampled from Hebbal (receiving a storm water drain) and Chowkalli lake (received
      domestic sewage and industrial effluents from various sources and was more
      polluted than Hebbal lake). It revealed noticeable differences in hemoglobin
      content, RBC and WBC count, and PCV and MCHC values. Severe anemia can be marked
      by a significant decrease in RBC count (p < 0.5), hemoglobin content, and PCV and
      MCHC values, whereas an increase in leukocyte count and MCV values were observed
      in fish from Chowkalli lake. Fish from lake B had fewer RBC and low concentration
      of serum protein and cholesterol. Serum concentration of glucose showed initial
      higher levels and then low concentration (900-1,500 g) in fish from lake B when
      compared to lake A. The variation in values of different parameters can be
      attributed to exposure of fish to various types of pollutants present mainly in
      the Chowkalli lake which receives heavy metals, synthetic detergents, petroleum
      products, and other acid and alkali substances from the nearby local industries.
      Other observations of these fish include dark body color and aggressive nature of
      fish.

PMID- 19603277
TI  - Construction of fuzzy membership functions for urban vehicular exhaust emissions
      modeling.
AB  - This paper presents a method for constructing a membership function (MF) for the
      fuzzy sets that expert systems deal with. This paper introduces a Bezier curve
      based mechanism for constructing MFs of convex normal fuzzy sets. The mechanism
      can fit any given data set with a minimum level of discrepancy. In the absence of
      data, the mechanism can be intuitively manipulated by the user to construct MFs
      with the desired shape. MFs have been developed using the proposed mechanism for
      urban vehicular exhaust emission modeling. It has been observed that all
      meteorological and vehicular parameters have either S-shaped MFs or Z-shaped MFs.
      Gaussian MF has been mostly applied for modeling air quality. The present study
      explored the application of fuzzy MF to analyze air pollution data from vehicular
      emission. The study reveals that S-shaped and Z-shaped MF can be used in addition
      to Gaussian MF.

PMID- 19603278
TI  - Macroalgae and DGT as indicators of available trace metals in marine coastal
      waters near a lead-zinc smelter.
AB  - The levels of Cd, Cu, Pb, and Zn were determined in the commonest species of
      green, red, and brown algae collected from five coastal sites in south-western
      Sardinia (Italy), an area with a long history of mining and smelting. The
      usefulness of employing Enteromorpha sp. and Padina pavonica (L.) Thivy to
      monitor metal pollution was evaluated, while diffusive gradients in thin films
      (DGT) devices were used to measure dissolved metals in seawater. Levels of Cd and
      Pb were high enough to be of environmental concern in the whole study area. A
      significant relationship was found between the content of Pb in P. pavonica and
      DGT-labile Pb in seawater, suggesting that gross elemental concentrations of
      nonessential metals such as Pb in algal tissues are apparently controlled by the
      abundance of dissolved metal species in the ambient seawater. The results pointed
      out the usefulness of using both DGT and algal methods for a better understanding
      of trace metal availability in coastal waters.

PMID- 19603272
TI  - Current understanding of risk factors for ovarian cancer.
AB  - OPINION STATEMENT: Ovarian cancer is the deadliest gynecologic cancer. Unlike
      many cancers such as breast, cervical and colon cancers, there is no easily
      clinically identifiable pre-malignant phase of this malignancy making early
      identification difficult. Similarly, unlike lung, head and neck, and skin
      cancers, there is not easily identifiable risk factor making prevention short of
      oophorectomy difficult. Even so, theories as to the causative factors of ovarian
      cancer continue to evolve making our understanding of the genesis of ovarian
      cancer more clear. Genetics, parity, environment, hormonal factors, and
      inflammation all play an important and pivotal role in the development of ovarian
      cancer. The most current understanding of these elements and their respective
      contribution to the development of this cancer are presented in this chapter.

PMID- 19603280
TI  - Quantifying nickel in soils and plants in an ultramafic area in Philippines.
AB  - In this study, concentrations of nickel (Ni) were quantified in the soils and
      plants in the agricultural areas of Salcedo watershed in Eastern Samar Island,
      Philippines. The quantity of total Ni in soils (TS-Ni) was significantly high
      with a mean of 1,409 mg kg(-1), while the soil available Ni (SA-Ni) was low with
      a mean of 8.66 mg kg(-1). As the levels of TS-Ni in the Salcedo watershed greatly
      exceeded the maximum allowable concentrations for agricultural soils, the site is
      not suitable for agricultural purposes. Despite significant TS-Ni levels, SA-Ni
      levels were very low due to tight binding between Ni and soil components.
      Consequently, all plants investigated did not meet the criterion for a Ni
      hyperaccumulator plant with low Ni contents (mean TP-Ni of 14.7 mg kg(-1)).
      Comparison of Ni levels between food plants and its recommended daily intake
      (RDI) suggests that consumption of food-plants grown in the study area is
      unlikely to pose health risks. However, caution must be taken against combined
      consumption of food plants with high Ni levels or their prolonged consumption, as
      it can induce accumulation of Ni above RDI.

PMID- 19603279
TI  - Fractions and leaching characteristics of mercury in coal.
AB  - A huge amount of coal is always stored in open spaces in coal-fired power plants
      before combustion. Mercury released from coal by rain or flowing water is an
      environmental risk and can cause contamination of the soil around the storage
      area. To better understand mercury pollution and to control mercury emission
      before combustion, it is necessary to determine the mobility and leaching
      characteristics of mercury from coal. In this study, we collected ten coal
      samples from one coal-fired power plant and proposed a sequential extraction
      procedure to get five fractions of mercury for evaluation. Elemental Hg was found
      as the most dominant fraction, and sulfate Hg was shown to be the second largest
      fraction. The mercury in the organic and the soluble fractions were not the major
      fractions, but they should still be considered because of their high mobility.

PMID- 19603281
TI  - Trace metals solubility in rainwater: evaluation of rainwater quality at a
      watershed area, Istanbul.
AB  - In this study, 79 bulk precipitation samples were collected at two sampling sites
      near Buyukcekmece Lake, one of the important drinking water sources of Istanbul,
      for the period of October 2001 to July 2002. The study comprised the
      determination of trace and toxic metals concentrations in rain water. The
      concentrations of the metals in this study were found to be higher than those
      reported by other researchers around the world. The solubility of toxic metals
      was found in the order of Cd>Cu>V>Zn>Ni>Pb>Cr. Solubility of metals under acidic
      conditions (pH<5.5) was approximately five times higher than those under neutral
      conditions with Cd as the most soluble metal (50% soluble). Statistical
      evaluations including seasonal variations, crustal enrichment factors, and
      correlation matrix were discussed to identify the possible sources of these
      pollutants. The study revealed that anthropogenic elements were highly enriched
      especially for Cd>Cu>Pb which were found to be highly enriched. Significant
      portion of Cu and Pb could be increased by the effect of local sources like
      cement industry in the area; however, the rest of the investigated trace metals
      could be brought to the sampling site by long-range transport to the Buyukcekmece
      Lake watershed area.

PMID- 19603282
TI  - Suppression of growth of highly-metastatic human breast cancer cells by
      norcantharidin and its mechanisms of action.
AB  - The effects of norcantharidin (NCTD) on the growth of highly-metastatic human
      breast cancer cells were investigated by in vitro and ex vivo assays. Our results
      indicated that norcantharidin inhibited the in vitro growth of human breast
      cancer MDA-MB-231 cell line in dose- and time-dependent manners after the cancer
      cells were treated with norcantharidin at the concentrations of 6, 30 and 60
      mumol/L for 24, 48 and 72 h. Moreover, the sera from the NCTD-treated rabbits
      after intravenous injection of NCTD at 15 and 30 min significantly suppressed the
      growth of the cancer cells ex vivo. The analyses by Hoechst 33258 staining and
      flow cytometry showed that the typical apoptotic morphological changes appeared
      and cell cycles arrested at G2/M phase in MDA-MB-231 cells after the cells were
      treated for 48 h with NCTD. In addition, NCTD down-regulated the expressions of
      anti-apoptotic protein Bcl-2 and up-regulated the expressions of pro-apoptotic
      protein Bax, eventually leading to the reduction of Bcl-2/Bax ratio in MDA-MB-231
      cells. Furthermore, NCTD at concentrations of 6, 30 and 60 mumol/L dose
      dependently reduced the phosphorylation of Akt and NF-kappaB expression in the
      breast cancer cell line. Induction of apoptosis and cell cycle arrest as well as
      reduction of Bcl-2/Bax ratio by NCTD may be the important mechanisms of action of
      NCTD suppressing the growth of MDA-MB-231 cells, which are associated with
      inhibition of the Akt and NF-kappaB signaling. Our findings suggest that
      norcantharidin may have a wide therapeutic and/or adjuvant therapeutic
      application in the treatment of human breast cancer.

PMID- 19603284
TI  - Steady state growth space study of Lactococcus lactis in D-stat cultures.
AB  - Growth space of Lactococcus lactis subsp. lactis IL1403 was studied at constant
      growth rate using D-stat cultivation technique. Starting from steady state
      conditions in a chemostat culture (mu = 0.2 h(-1)), the pH and/or temperature
      were continuously changed in the range of 5.4-6.4 and 26-34 degrees C,
      respectively, followed by the return to the initial environmental conditions.
      Based on substrate consumption and product formation yields and expression
      changes of 1,920 genes, it was shown that changes of physiological state were not
      dependent on the direction of movement (from pH 6.3 to 5.4 or from 5.4 to 6.3),
      showing that quasi steady state values in D-stat corresponded to the steady state
      values in chemostats. Relative standard deviation of growth characteristics in
      triplicate D-stat experiments was below 10%. Continuing the experiment and
      reestablishing initial growth conditions revealed in average 7% difference
      (hysteresis) in growth characteristics when comparing chemostat steady state
      cultures prior and after the change of environmental conditions. Similarly,
      shifts were also seen at gene expression levels. The large amount of
      quantitatively reliable data obtained in this study provided a new insight into
      dynamic properties of bacterial physiology, and can be used for describing the
      growth space of microorganisms by modeling cell metabolism.

PMID- 19603283
TI  - Morpho-functional study of thyroids from calves suspected to be treated with
      anabolic substances.

PMID- 19603285
TI  - Production of oogonia and oospores of Leptolegnia chapmanii Seymour
      (Straminipila: Peronosporomycetes) in Aedes aegypti (L.) larvae at different
      temperatures.
AB  - The aquatic oomycete fungus Leptolegnia chapmanii Seymour is pathogenic to
      mosquito larvae, but it has been little studied since it was first isolated.
      Although studies have been performed on different biological isolates of L.
      chapmanii around the world, they were made on zoospores and a very little or even
      nothing is known about the sexual stage (oogonia and oospores), which allows L.
      chapmanii to remain in the environment when conditions are not favorable. The
      main objective of this study was to determine the relationship between
      temperature and time of onset of L. chapmanii oogonia and oospores in Ae. aegypti
      larvae. Leptolegnia chapmanii-infected IV instar Ae. aegypti larvae were
      incubated at different temperatures between 5 and 45 degrees C and photoperiod
      controlled for 90 days. The number of oogonia and oospores was examined daily for
      each tested temperature. As was expected, low temperatures extended the times of
      oogonia formation, as much as seven times. Likewise, temperatures significantly
      affect the number of oogonia produced.

PMID- 19603286
TI  - Comparison of approaches for efficient gene silencing induced by microRNA-based
      short hairpin RNA and indicator gene expression.
AB  - MicroRNA-based short hairpin RNAs (shRNAs) are natural inducers of RNA
      interference and have been increasingly used in shRNA expression strategies. In
      the present study, we compared the efficiencies of exogenous green fluorescence
      protein (GFP) and endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      knockdown and red fluorescent protein (RFP) indicator expression mediated by
      three differently designed plasmids. RFP was introduced either at the 5' end, at
      the 3' end of the human mir155-based target gene (TG) (e.g., GFP or GAPDH) shRNA
      expression cassette (EC), or at the 3' end of the chimeric intron-containing TG
      shRNA EC. Comparisons with the control vector showed an obvious reduction of GFP
      or GAPDH expression with the various shRNA expression plasmids (P < 0.05). When
      RFP was located at the 5' end or at the 3' end of the TG shRNA EC, RFP expression
      was low; whereas when RFP was connected with the chimeric intron-containing TG
      shRNA EC, RFP expression was high. Taken together, this study demonstrated an
      efficient plasmid design for both TG silencing induced by microRNA-based shRNA
      and indicator gene expression in vitro.

PMID- 19603287
TI  - Expression and purification of recombinant arginine decarboxylase (speA) from
      Escherichia coli.
AB  - The crystal structures of almost all the enzymes of arginine metabolism have been
      determined, but arginine decarboxylase's structure is not resolved yet. In order
      to characterize and crystallize arginine decarboxylase, we overexpressed
      biosynthetic arginine decarboxylase (ADC; EC 4.1.1.19, encoded by the speA gene)
      from Escherichia coli in the T7 expression system as a cleavable poly-His-tagged
      fusion construct. The expressed recombinant His(10)-ADC (77.3 kDa) was first
      purified by Ni-NTA affinity chromatography, then proteolytically digested with
      Tobacco Etch Virus (TEV) protease to remove the poly-His fusion tag, and finally
      purified by anion exchange chromatography. The His(10) tag removed recombinant
      ADC (74.1 kDa)'s typical yield was 90 mg from 1 l of culture medium with purity
      above 98%. The recombinant ADC was assayed for decarboxylase activity, showing
      decarboxylase activity of 2.8 U/mg, similar to the purified native E. coli ADC.
      The decarboxylase activity assay also showed that the purified recombinant ADC
      tolerated broad ranges of pH (pH 6-9) and temperature (20-80 degrees C). Our
      research may facilitate further studies of ADC structure and function, including
      the determination of its crystal structure by X-ray diffraction.

PMID- 19603288
TI  - Private cord blood banking: current use and clinical future.
AB  - International private umbilical cord blood banking has expanded rapidly in recent
      years since the first cord blood transplant which was 20 years ago. Private
      companies offer parents the opportunity to store umbilical cord blood for the
      possible future use by their child or other family members. The private cord
      blood industry has been criticised by a number of professional bodies including
      the EU Ethics Committee, the Royal College of Obstetrics and Gynaecology, the
      Royal College of Midwives and the US College of Paediatrics. This review presents
      the arguments from the opponents of private cord blood banking, and then makes
      the case for private cord banking based on the latest scientific and clinical
      evidence.

PMID- 19603290
TI  - [Guillain-Barre syndrome and IVIg: does early initiation of treatment influence
      the mean hospital stay?].
AB  - INTRODUCTION: Treatment with intravenous immunoglobin (IVIg) in the first two
      weeks of hospitalization has proven efficiency for shortening recovery time of
      patients with Guillain- Barre syndrome (GBS). The goal of the study is to
      determine if early treatment with IVIg in the first days after onset of symptoms
      has a significant effect on shortening average length of hospital stay. METHODS:
      We examined retrospectively the records of 69 patients with GBS. Group A (9
      patients) received no treatment with IVIg, Group B (31 patients) received
      treatment on the sixth day or thereafter and Group C (29 patients) received
      treatment in the first five days from symptoms onset. RESULTS: Mean duration of
      hospitalisation time for Group A was 47.4 days, for Group B it was 32.4 days and
      for Group C, 21.3 days (p < 0.001). In summary, treatment with IVIg in the first
      five days after the onset of GBS symptoms reduces the length of hospitalisation
      by 11 days. Given the retrospective nature of our study, these findings should be
      confirmed in a prospective, randomised, multicentric study.

PMID- 19603291
TI  - [Review of the economic evidence on the use of deep brain stimulation in late
      stage Parkinson's disease].
AB  - INTRODUCTION: The purpose of this article is to present the results of a
      systematic review on the costs and the efficiency of Deep Brain Stimulation (DBS)
      on patients suffering advanced Parkinson's disease. MATERIAL AND METHOD: A
      systematic review is performed using databases such as Medline, NHS EED and HTA
      del Centre for Reviews and Dissemination and Google Scholar from January 2001
      2008. RESULTS: Ten articles meet the criteria; one cost description, four cost
      analyses and five economic evaluations. The scientific evidence shows a reduction
      in the pharmaceutical costs of those patients treated with DBS. Regarding the
      direct medical costs, the same statement cannot be made. While some studies
      estimate the equivalent annual cost of DBS is 54,7% higher than that of
      traditional therapy, other studies, which include indirect costs such as
      productivity losses or informal care, claim DBS costs 34,7% less. The incremental
      cost-effectiveness ratio per QALY is slightly above euro30.000 in 1998 in both
      the cost-utility analyses where the time horizon was 5 years or more. In the
      third cost-utility analysis, DBS is the dominant option when the equivalent
      annual cost was computed. CONCLUSIONS: The available evidence is not strong
      enough to conclude whether DBS' direct medical costs are higher or lower than the
      costs of traditional therapy. Key words: Parkinson's disease. Deep brain
      stimulation. Subthalamic stimulation. Cost analysis. Economic evaluation.

PMID- 19603292
TI  - [Restless legs syndrome. Features and impact on sleep].
AB  - INTRODUCTION: Restless legs syndrome (RLS) is a chronic neurological disorder
      that has a negtive influence on sleep. We describe clinical spectrum,
      polysomnogram and impact on sleep of patients' series with RLS. METHODS: We
      studied 49 patients with RLS. We analyse socio- demographic information, clinical
      features, therapy and impact on sleep. We realized differents questionnaire:
      Index of Severity of Sleep, Epworth Scale, Index-RLS, Questionnaire Quality of
      Life-RLS and Questionnaire from limitation of laboral productivity. RESULTS: Mean
      age is 60.33+/-14.27 with similar distribution enter gender. They presented a
      positive family history in 36,73% with predominant in early onset of symptoms.
      Secondary causes more frequent associated were rheumatoid arthritis, iron
      deficiency, uremia, pregnancy and polineuropathy. Significative prevalence of
      insomnia (73,43%) and periodic limb movement disorder (51,02%), obstructive sleep
      apnea syndrome (22,45%) and hipersomnia (22,45 %). Pharmacological treatment more
      used were dopaminergic drugs. We didn't find significant stadistic differences
      enter clinical feature and therapy, so tendency to better quality of life with
      dopaminergic drugs. CONCLUSIONS: It's an neurological disorder with important
      delay in diagnosis. Early detection is needed because important impact on sleep
      efficiency and quality of life, and improvement with therapy, solely dopaminergic
      drugs.

PMID- 19603293
TI  - [Immunohistochemical expression of progesterone receptor in relationship with
      histological grade and risk of relapses in intracranial meningiomas].
AB  - INTRODUCTION: Meningiomas are frequent primary neoplasms of the central nervous
      system, usually benign and susceptible to healing through surgery. The
      histological grade of the WHO and the extension of the initial surgical resection
      are determining prognostic factors in these tumors. Nevertheless, a recurrence
      rate close to 20 % in benign meningiomas completely diseccated arises the need of
      considering new prognostic factors. METHODS: A total of 93 cases were selected
      for the immunohistochemical study of the progesterone receptor (PR) in relation
      to the histological grade and the risk of recurrencies in meningiomas. RESULTS:
      Though the immunohistochemical labelling index (LI) of the PR decreased with the
      progression of the histological grade (means of 27.37 % for grade I, 17.89% for
      grade II, and 13.50% for grade III), such correlation was not statistically
      significant and the cut off estimated in 20% was not satisfactory to discriminate
      among benign meningiomas (grade I) and non benign (grades II-III) due to its poor
      sensitivity (56.10%) and positive predictive value (56.10 %). The comparison of
      the LI of the PR among non recurrent meningiomas (36.35 %) and recurrent (22.10%)
      was neither statistically significant, but permitted to establish a useful cut
      off of 40% (LI >40% in 13/23 non recurrent tumors and <40% in 19/23 recurrent
      tumors) with a sensitivity of 82.61% and a positive predictive value of 65.52%.
      CONCLUSION: The LI of the PR is apparently not related to the histological grade
      of the meningiomas, but is significantly smaller in recurrent meningiomas. A
      meningioma with a LI of the PR less than 40 % suggests the risk of recurrences.

PMID- 19603294
TI  - [Enterococcal meningitis in adults].
AB  - INTRODUCTION: In recent years, Enterococcus species have emerged as significant
      human pathogens capable of causing a variety of nosocomial and community-acquired
      infections. However, enterococcal meningitis (EM) is an uncommon disease. This
      study describes the clinical features and outcome of EM in adults seen at a
      tertiary hospital during 25 years. METHODS: We reviewed the charts of all
      patients (aged > or = 14 years) evaluated between 1982 and 2006 with EM. RESULTS:
      Six cases of EM were diagnosed (4,2% of culturepositive bacterial meningitis),
      with a mean age of 67 years (range, 47-83). All cases had postoperative
      meningitis, and the most common predisposing condition was the presence of CSF
      devices (5 cases). The clinical course was acute (duration of symptoms of one day
      in 5 cases). Most patients presented with fever and headache (5 cases), and
      changes in mental status (4 cases). The most common CSF abnormalities were
      pleocytosis (6 cases), elevated protein level (6 cases), and hypoglycorrhachia (3
      cases). Gram CSF stain was positive in one case, and culture in all cases (4 were
      E. faecalis and 2 were E. faecium). Treatment included vancomycin (5 cases) or
      ampicillin plus gentamicin (one case), CSF devices were removed in all patients,
      and there were no deaths or sequelae. CONCLUSIONS: EM is an uncommon disease,
      most of cases had a postoperative origin, and CSF devices are the most common
      predisposing condition. A favourable outcome was observed in the cases reported.

PMID- 19603295
TI  - [Quality of neurological care in the emergency services: a study from the
      community-hospital].
AB  - INTRODUCTION: The medical conditions shared by hospital emergency services and
      community-hospital neurology clinics (CHNC) have not been described, and the
      quality of the medical care received in these conditions has not been evaluated
      in our environment. METHODS: Over a 2 month period, those patients presenting at
      any of the seven CHNC in a Health Care Area 1 of Madrid due to previously
      attended medical conditions in the emergency services were systematically
      registered. The area neurologists of the CHNC collected administrative and
      clinical variables and made a judgment on the medical care (primary outcome
      measure) and diagnoses (secondary outcome measure) received. RESULTS: A total of
      181 patients were included (mean age: 58 years; 60% women). The inclusion rate
      was one patient per working day, and 31% of patients were visited out of the
      established quota number of patients for the clinic. The most frequent reasons
      for visiting the emergency room were: headache (20%), focal neurological syndrome
      (16%) and loss of consciousness (14%). The most frequent diagnoses at the CHNC
      were: primary headache (19 %), stroke (11%) and epilepsy (9 %). Emergency care
      was deemed correct in 56 % of patients. When the patients with intervention were
      compared to those with no intervention, participation of the neurology service in
      the emergency room was associated to a greater percentage of correct diagnoses
      (59% vs. 41%; p=0.019) and care (69% vs. 47%; p=0.003). CONCLUSIONS: The medical
      conditions shared with the emergency services represent a small but relevant
      proportion of the patients assisted in the CHNC. Some of these conditions
      (primary headaches, syncopes) should be canalized into primary health care.
      Others (epilepsy) require a circuit between emergency room and CNNC, but the
      appointment system should be adapted. The intervention of a neurologist in the
      emergency room raises the quality of the care.

PMID- 19603296
TI  - [Experimental models in Alzheimer's disease].
AB  - INTRODUCTION: Alzheimer s disease (AD) is the most common neurodegenerative
      disease and (it accounts for 60-80 %). The certain diagnosis is made thanks to
      the brain patients study. Since 1970 there have been developed experimental
      models that have done a deep approach of this disease and new therapeutic
      researching. METHODS: We review all the papers published about experimental
      models in AD, and all the new therapeutical approaches base don them using the
      database Pubmed. RESULTS: Animal models aim to replicate the symptoms, the
      lesions or the cause(s) of AD. It has been described many experimental models in
      AD. There are animal models based on the metabolism of the amyloid precursor
      protein (APP) (human APPwild type wt- o the mutants forms), other based on
      Presenilin (PS) (transgenic mice that overexpress the form wild-type or the
      mutant ones), the double mutants PS/APP that develop the lesions earlier. There
      are other based on tau protein (tau-JNPL3) or the triple transgenic PS/APP/tau.
      There are also lines with altered expression of neprilysin, the main degrading
      enzyme of Abeta and also models based on APOE. Other models are rats, chick
      embryo, dog, primates and cetacean, cell culture of mature hippocampic neurons
      and the effects of the Abeta oligomers in them (soluble toxic species).
      CONCLUSIONS: Experimental models in AD have supposed a key tool in order to know
      deeply about neurodegenerative diseases, over all AD. Besides they allow us
      design new therapeutic approaches.

PMID- 19603297
TI  - [Papilloedema: true or false?].
AB  - INTRODUCTION: Papilledema may lead to diagnostic difficulties in its different
      stages. It should be differenciates from optic neuropathies and structural
      abnormalities of the optic disk known as pseudopapilloedema. The new diagnostic
      techniques in ophthalmology may be useful to diagnose papilloedema as well as in
      further follow-up, even though they are not exempt of limitations. DEVELOPMENT:
      Optical coherence tomography is a non-invasive inferometric optical tomographic
      imaging technique that provides cross-sectional in vivo images of the optic nerve
      and the retina. Measurements of the retinal nerve fiber layer thickness and its
      subsequent analysis are very useful to detect subtle changes of loss or
      thickening. Eye ultrasonography is the most reliable method to reveal buried
      drusen of the optic disk head, a major cause of pseudopapilloedema. Fluorescein
      angiography reveals abnormalities in retinal vessel permeability in different
      types of optic disk swelling, which is helpful to decide whether it is a true
      papilloedema or a pseudopapilloedema. CONCLUSIONS: Optical coherence tomography,
      ultrasonography and fluorescein angiography are low-invasive diagnostic
      techniques able to provide the clues to the correct diagnosis of true
      papilloedema at initial stages. They are also useful to rule out
      pseudopapilloedema and optic disk swelling secondary to other neuropathies.

PMID- 19603298
TI  - [Lepra: an uncommon cause of infectious neuropathy].
AB  - INTRODUCTION: Lepra is an uncommon disease within our setting. However, it was
      considered the most frequent cause of polyneuropathy only 50 years ago. CASE
      REPORT: We present the case of a 37 year-old woman who consulted due to
      paresthesias in both hands and feet, livedo reticularis and complaints of
      frequent hand lesions. Examination of the skin detected nodular lesions and the
      neurophysiological study confirmed distal symmetric sensitive polyneuropathy with
      axonal predominance. The skin biopsy also showed histocytic infiltrate and
      mycobacterium lepra type intracytoplasmatic bacilli. This led to the diagnosis of
      Multibacillary lepromatous leprosy. Multiple treatment was begun, according to
      the World Health Organization recommendations, with good evolution. In spite of
      the attempts to eradicate lepra, its incidence continues to be elevated,
      especially in endemic areas, among which the south of Spain is included. It is
      generally associated to overcrowding and low social-economic level. CONCLUSIONS:
      This is the last endemic case in the Valencian Community. The possibility of
      lepra should be considered among the possible causes of sensitive polyneuropathy,
      above all in patients in endemic areas.

PMID- 19603300
TI  - Nighttime maternal responsiveness and infant attachment at one year.
AB  - This study examined associations between mother-infant nighttime interactions and
      mother-infant attachment when infants were 12 months old. Forty-four mother
      infant pairs participated in this study. For three consecutive nights at home,
      babies were observed in their cribs using a digital video system. Mothers
      reported on their nighttime interactions with their babies using a self-report
      diary and completed a questionnaire regarding child temperament. Attachment was
      assessed in the Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978).
      Mothers of securely attached infants had nighttime interactions that were
      generally more consistent, sensitive and responsive than those of insecurely
      attached infants. Specifically, in secure dyads, mothers generally picked up and
      soothed infants when they fussed or cried after an awakening.

PMID- 19603301
TI  - Attachment to people and to objects in obsessive-compulsive disorder: an
      exploratory comparison of hoarders and non-hoarders.
AB  - People with Obsessive-Compulsive Disorder (OCD) who hoard have been posited to
      have an atypical emotional attachment to the inanimate objects that they
      pathologically accumulate, yet this hypothesis has not been formally examined
      using methodology from the attachment field. To explore this hypothesis,
      attachment to people and to inanimate objects was assessed in 30 individuals with
      OCD (n = 14 hoarders, n = 16 non-hoarders). Attachment was assessed using
      standard measures of interpersonal attachment: the Reciprocal Attachment
      Questionnaire and the Five Minute Speech Statement. These measures were adapted
      to evaluate inanimate object attachment as well. The data provides preliminary
      evidence that individuals who hoard report significantly higher levels of
      emotional over-involvement (EOI) with inanimate objects and lower levels of EOI
      with people than non-hoarders. Hoarders also reported significantly higher levels
      of care-seeking behavior from inanimate objects, and less effectiveness in making
      use of the inanimate object relationship in comparison to non-hoarders. Hoarding
      severity was correlated with significantly increased dysfunction in all of these
      areas. Fear of losing an inanimate object was found to significantly predict
      hoarding severity. In general, female participants had significantly higher mean
      ratings of interpersonal attachment insecurity than male participants, regardless
      of OCD symptomatology. Although limited in sample size and methodology, this
      study provides preliminary data on attachment style in people with OCD, and the
      data generate specific hypotheses about attachment in those who compulsively
      hoard that should be explored in future research.

PMID- 19603299
TI  - Attachment organization and patterns of conflict resolution in friendships
      predicting adolescents' depressive symptoms over time.
AB  - The current study examined the moderating effects of observed conflict management
      styles with friends on the link between adolescents' preoccupied attachment
      organization and changing levels of depressive symptoms from age 13 to age 18
      years. Adolescents and their close friends were observed during a revealed
      differences task, and friends' behaviors were coded for both conflict avoidance
      and overpersonalizing attacks. Results indicated that preoccupied adolescents
      showed greater relative increases in depressive symptoms when their friends
      demonstrated overpersonalizing behaviors, vs. greater relative decreases in
      depressive symptoms when their friends avoided conflict by deferring to them.
      Results suggest the exquisite sensitivity of preoccupied adolescents to qualities
      of peer relationships as predictors of future levels of psychological
      functioning.

PMID- 19603303
TI  - Mental representations of attachment in eating disorders: a pilot study using the
      Adult Attachment Interview.
AB  - Mental representations of attachment in a sample of adults with Eating Disorders
      (ED) were assessed using the Adult Attachment Interview (AAI). Sixty subjects
      participated in the study: 30 non-clinical and 30 clinical. The results obtained
      showed a specific distribution of attachment patterns in the clinical sample: 10%
      Free/Autonomous (F), 47% Insecure-Dismissing (Ds), 17% Insecure
      Entangled/Preoccupied (E) and about 26% disorganized (CC/U). The two samples
      differed in their attachment pattern distribution and were significantly
      different on some coding system scales. Further information was obtained by
      analyzing differences between the three ED subtypes considered (i.e. Anorexia
      Nervosa, Bulimia Nervosa and Binge Eating Disorder) and by investigating the
      differential role of the two parental figures in the definition of attachment
      representations. Results showed potential benefits in using the AAI coding system
      scales in addition to the main classifications in order to understand better the
      developmental issues involved in these disorders. Implications for developmental
      research and clinical nosology are discussed.

PMID- 19603302
TI  - Disorganized attachment, absorption, and new age spirituality: a mediational
      model.
AB  - In this paper, we present a theoretical model and an empirical review linking
      disorganized attachment with New Age spiritual beliefs and activities via a
      proposed mediator; the propensity to enter altered states of consciousness
      (absorption/dissociation). Utilizing a prospective longitudinal design (N = 62),
      an empirical test of the mediational model is also provided for illustrational
      purposes. More specifically, we tested if unresolved/disorganized (U/d)
      attachment scores, as identified via the Adult Attachment Interview at the first
      assessment point, predicted New Age spirituality 3 years later, and whether this
      link was mediated by absorption. Results supported the mediational model,
      although the bivariate relation between U/d attachment and New Age spirituality
      was of modest strength. The discussion focuses on the general implications,
      clinical as well as non-clinical, of the proposed model. Finally, we argue that
      time is now ripe for attachment researchers to address additional non
      pathological sequelae of disorganized attachment and the related propensity to
      experience altered states of consciousness.

PMID- 19603304
TI  - Increased hemoglobin associated with VEGF inhibitors in advanced renal cell
      carcinoma.
AB  - We retrospectively analyzed whether increased hemoglobin is a surrogate biomarker
      of efficacy for vascular endothelial growth factor (VEGF) inhibitors in advanced
      renal cell carcinoma (RCC) patients. Twelve patients were identified who had
      received bevacizumab alone or as combination therapy. Eleven patients experienced
      a rise in hemoglobin. Median change was 1.6 g/dL (0-4.0). Degree of peak increase
      correlated with longer progression-free survival (PFS) in metastatic patients:
      increase of < 15% yielded a 3.1-month median PFS compared to 8.2 months with
      rises > 15%. This study identifies increased hemoglobin as a possible consequence
      of VEGF inhibitors. The correlation with longer PFS suggests that rise in
      hemoglobin may be a surrogate biomarker of efficacy.

PMID- 19603305
TI  - An object-oriented modelling framework for the arterial wall.
AB  - An object-oriented modelling framework for the arterial wall is presented. The
      novelty of the framework is the possibility to generate customizable artery
      models, taking advantage of imaging technology. In our knowledge, this is the
      first object-oriented modelling framework for the arterial wall. Existing models
      do not allow close structural mapping with arterial microstructure as in the
      object-oriented framework. In the implemented model, passive behaviour of the
      arterial wall was considered and the tunica adventitia was the objective system.
      As verification, a model of an arterial segment was generated. In order to
      simulate its deformation, a matrix structural mechanics simulator was
      implemented. Two simulations were conducted, one for an axial loading test and
      other for a pressure-volume test. Each simulation began with a sensitivity
      analysis in order to determinate the best parameter combination and to compare
      the results with analogue controls. In both cases, the simulated results closely
      reproduced qualitatively and quantitatively the analogue control plots.

PMID- 19603306
TI  - Modal behaviour of bones during fracture.
AB  - A common cause of human disability is related to the fracture of bones, complex
      structural materials whose properties vary with time. An analytical study (using
      ANSYS, a commercial finite element package) of bones under fracture conditions is
      presented, focusing on the frequency variation versus depth of crack, as well as
      on the evolution of strength in the fracture area.

PMID- 19603307
TI  - Generation of 5 and 17 kDa human growth hormone fragments through  limited
      proteolysis.
AB  - INTRODUCTION: The reported presence of two fragments of 5 and 17 kDa originating
      from the 22 kDa human growth hormone (hGH) in blood and tissues, postulated as
      the sequences AA 1-43 and AA 44-191, has led to the hypothesis of a post
      translational proteolytic origin with respect to the abundant 22 kDa variant (AA
      1-191). To evaluate this hypothesis, the activity of several endo-proteases on
      the 22 kDa hGH protein has been evaluated. METHODS: Proteolysis using pepsin,
      trypsin, V8-protease, proteinase K and thermolysin were explored under several
      conditions, including incubation time and pH. Results were monitored by MALDI-TOF
      and HPLC-ESI mass spectrometry. Proteolytic 5 and 17 kDa fragments were purified
      through reversed phase HPLC-UV, and their immuno-affinity properties evaluated by
      surface plasmon resonance. RESULTS: Thermolysin was shown to target mainly the AA
      43-44 bond of the 22 kDa sequence at physiological pH. Interaction studies of the
      purified fragments with anti-GH antibodies showed some reactivity for the 17 kDa
      fragment. CONCLUSIONS: Thermolysin processes hGH generating 5 and 17 kDa
      fragments, demonstrating the feasibility of this reaction, although the enzyme
      responsible for this process in humans is still unknown. Specific antibodies
      should be used to detect these fragments in human specimens, and, at the same
      time, the 17 kDa fragment could constitute an interference in some hGH
      immunoassays.

PMID- 19603309
TI  - Combined fractional laser treatment with 1550-nm erbium glass and 10 600-nm
      carbon dioxide lasers.

PMID- 19603308
TI  - Plaque stage mycosis fungoides treated with bexarotene at low dosage and UVB-NB.
AB  - Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma
      (CTCL), a non-Hodgkin lymphoma characterized by proliferation of atypical
      epidermotrophic helper/memory T cells in the skin. Therapeutic management
      includes topical therapy such as topical corticosteroids, topical chemotherapy or
      phototherapy; or systemic therapy such as photochemotherapy (psoralen and
      ultraviolet A [PUVA]), extracorporeal phototherapy, radiation, and mono or
      polychemotherapy. Herein we report one case of MF unresponsive to conventional
      therapy, subsequently treated with bexarotene and narrow-band ultraviolet B (UVB
      NB). Bexarotene belongs to a new subclass of retinoids, binding primarily the
      nuclear hormone receptors RXRs. Bexarotene has the same effect as its natural
      counterpart: 9-cis-retinoic acid. Bexarotene may be used alone or in association
      with interferon alfa, interferon gamma, extracorporeal photophoresis and PUVA. We
      utilized 75 mg/day of bexarotene associated with 0.3 J/cm(2) UVB-NB as an initial
      dose. The sessions were three times weekly and the irradiation was increased by
      30% at each session to reach a maximum of 1.6 J/cm(2). After 8 week treatment,
      clinical lesions markedly improved without recording hypercholesterolemia or
      hypothyroidism. During the follow-up no relapses were detected. We suggest that
      the combined therapy UVB-NB and bexarotene may be considered as an alternative
      treatment to PUVA and bexarotene.

PMID- 19603310
TI  - Future recruitment into obstetrics and gynaecology: factors affecting early
      career choice.
AB  - Medical students attending a careers talk in obstetrics and gynaecology at
      Nottingham University were approached in this survey, to identify factors which
      influenced an early career choice in O&G. We received 60 responses, giving a
      response rate of 83.3%. The positive factors that encouraged an early career
      choice of O&G were: a positive undergraduate O&G attachment; consultant and
      junior doctor role-models; a good mix of medicine and surgery; availability of
      hands-on opportunities and early career advice. The perception of long working
      hours was not a negative influence. Male medical students were put-off by the
      lack of opportunity to undertake pelvic examinations.

PMID- 19603312
TI  - Pregnancy outcome after age 40 and risk of low birth weight.
AB  - A historical cohort study was conducted to examine the pregnancy outcome in women
      aged 40 or older and determine the effect of age on low birth weight. The
      pregnancy outcomes of 789 mothers aged 40 years or older were analysed and
      compared with those of 20,852 mothers aged 20-34 years. There were differences in
      socioeconomic status and obstetric characteristics between the two groups. The
      older group had more medical and obstetric complications (diabetes mellitus,
      chronic hypertension, malpresentation, pregnancy-induced hypertension, placenta
      praevia, multiple pregnancies, pre-term labour, fetal distress, retained
      placenta, postpartum haemorrhage and endometritis), more adverse fetal outcomes
      (low birth weight, low Apgar scores and congenital anomalies) and a higher
      caesarean section rate. The multivariate logistic regression analysis confirmed
      that maternal age was an independent risk factor for low birth weight. These data
      will be useful in counselling patients about their expectations and the risk of
      adverse outcomes and in providing the appropriate necessary care.

PMID- 19603313
TI  - Sheffield modified technique for external cephalic version.
AB  - External cephalic version (ECV) is the manipulation of the fetus, through the
      maternal abdomen, to a cephalic presentation. The incidence of caesarean section
      for breech presentation has increased markedly in the last 20 years. External
      version has become more popular in the past 10 years because of the increasing
      evidence of risks from vaginal breech delivery, increasing demand on the
      reduction of caesarean sections, a strong safety record, and high success rate of
      ECV of up to 80%. The use of external cephalic version can produce considerable
      cost savings in the management of the breech presentation at term; however, there
      is a wide variation in the success rate, with a range between 30-80%. The ECV
      technique has remained unchanged for many generations without any modification.
      This paper provides the outcome of a small prospective study implementing a
      modified technique for ECV, which has a high success rate.

PMID- 19603311
TI  - US obstetrician-gynaecologist's prevention and management of obesity in
      pregnancy.
AB  - A survey regarding management of obesity in pregnancy was mailed to 787
      practising members of the American College of Obstetricians and Gynecologists
      (ACOG); 433 responded of whom 353 practised obstetrics. Most (79.2%) had read
      ACOG Committee Opinion, 'Obesity in Pregnancy,' and rated it helpful (68.6%) or
      very helpful (17.2%). Most responding physicians (91.2%) use BMI to assess their
      patients weight status; fewer (63.4%) use pre-pregnancy BMI to modify their
      pregnancy weight gain recommendation. Having read the Committee Opinion and being
      a woman were independent factors associated with using pre-pregnancy BMI.
      Responding physicians that had read the Committee Opinion were more knowledgeable
      about obesity-related pregnancy complications; but even among those physicians,
      only 32.2% were aware that maternal obesity is a risk factor for fetal neural
      tube defects. The responding physicians appeared well-versed on appropriate
      practice for caesarean delivery for obese patients whether they had read the
      Committee Opinion or not.

PMID- 19603314
TI  - Transvaginal measurement of cervical length in the prediction of successful
      induction of labour.
AB  - A total of 100 women with gestational ages of 34-42 weeks requiring induction of
      labour were consecutively recruited in a prospective study at the Medical College
      and Hospital, Baroda, India. The aim of this study was to determine the value of
      transvaginal measurement of cervical length in the prediction of successful
      vaginal delivery within 24 h. Induction of labour was carried out with Tab
      Misoprostol (25 microg). A Bishop's score and sonographic cervical assessment
      were performed prior to induction. Univariate and logistic regression analyses
      was used. A pre-induction cervical length measurement on TVS was an independent
      predictor of successful vaginal delivery. At < or =3 cm cervical length, the
      probability of a LSCS was <30%, while with 4 cm cervical length, the probability
      became >75%. One unit increase in cervical length increased the probability of
      LSCS by 45%. The cervical length measurement by TVS is therefore an independent
      predictor of successful labour induction and performs better than Bishop's score
      as a method of pre-induction cervical assessment.

PMID- 19603315
TI  - Trends of different forms of anaesthesia for caesarean section in South-eastern
      Nigeria.
AB  - General anaesthesia is recognised as a cause of maternal mortality/morbidity in
      caesarean deliveries, and regional anaesthesia is believed to reduce anaesthesia
      related maternal/fetal morbidity and mortality. The aim of this study is to
      present the trends of different forms of anaesthesia for caesarean section in
      Eastern Nigeria. We conducted a retrospective survey of hospital records of
      caesarean deliveries in this unit over a 4-year period from January 2003 to
      December 2006. There were 2,968 deliveries and 3,140 births (2,959 live births),
      with 729 women (24%) delivered by caesarean section. There was a yearly increase
      in the use of regional anaesthesia from 18% in 2003 to 48% in 2004 and 72.6% in
      2005, but it fell to 71% in 2006. There were 59 stillbirths giving a stillbirth
      rate of 81/1,000 caesarean deliveries. The total number of stillbirths in the
      hospital during the study period was 179 giving a stillbirth rate of 60/1,000
      deliveries. A total of 42 (71%) stillbirth deliveries were associated with
      general anaesthesia and 17 (29%) associated with spinal anaesthesia. Of the 32
      neonates with an Apgar score of 3-5 at 5 min after birth, 21 (66%) delivered
      under general anaesthesia and 11 (34%) delivered under spinal anaesthesia. There
      were eight hysterectomies in patients with ruptured uterus, all under general
      anaesthesia. There was one maternal death in a patient who was delivered under
      general anaesthesia. The fetal loss in this study is high and may indicate that
      most data on stillbirths from parts of the developing world may be
      underestimates. In conclusion, in developing country such as Nigeria there is a
      changing trend towards the use of regional anaesthesia during caesarean section.
      Its use should be encouraged in the developing world, especially resource-poor
      environments because it is cheaper to provide.

PMID- 19603316
TI  - A randomised controlled trial comparing the efficacy of intramuscular
      syntometrine and intravenous syntocinon, in preventing postpartum haemorrhage.
AB  - This randomised controlled trial aimed to compare the efficacy of intramuscular
      syntometrine with intravenous syntocinon, in preventing postpartum haemorrhage. A
      total of 686 women were randomised into two groups; one receiving intramuscular
      syntometrine and the other receiving intravenous syntocinon, as part of the
      active management of the third stage of labour. There was no difference in the
      mean blood loss between the two groups. However, there was an increased incidence
      of having a diastolic blood pressure of >90, 30 min after the delivery (p =
      0.004), with intramuscular syntometrine. Therefore, it can be concluded that 1 ml
      of intramuscular syntometrine and 10 units of intravenous syntocinon are equally
      effective in preventing postpartum haemorrhage.

PMID- 19603317
TI  - A new uterine suture technique to control PPH in congenitally malformed uterus
      during caesarean section.
AB  - The objective of this prospective study was to evaluate the efficacy of
      simultaneous devascularisation and compression suture for the control of PPH in a
      congenitally malformed uterus during caesarean section while classic management
      failed. The technique adopted for devascularisation was ligation of uterine
      arteries bilaterally below the hysterotomy wound and for the compression of the
      uterine musculature, suture passing through and through the anterior and
      posterior wall above the hysterotomy wound closed to either side, tied
      anteriorly. The majority (75%) of the women were primigravida and mostly
      presented with malpresentation of the fetus. Mothers were in the age group of 19
      24 years. Out of eight cases, four (50%) cases had a bicornuate uterus, two cases
      had unicornuate and two had a sub-septate uterus. This procedure was effective in
      87.5% (7/8) of cases. In follow-up, normal puerperium, menstruation and pregnancy
      were observed. This procedure is a simple, effective and safe technique to
      control PPH in congenitally malformed uterus in the field of conservative
      surgical approaches.

PMID- 19603318
TI  - Echogenic yolk sac: a marker for aneuploidy?

PMID- 19603319
TI  - Do colour and personality influence treatment seeking behaviour in women with
      lower urinary tract symptoms? A prospective study using the short Luscher colour
      test.
AB  - Lower urinary tract symptoms (LUTS) are common and affect quality of life. The
      influence of personality on the patients' decision to seek help is poorly
      understood. The aim of this study was to identify personality traits which may
      influence womens' decision to seek help for LUTS using the short Luscher colour
      test (LCT). Participants completed two validated questionnaires prior to taking
      part in the LCT. Symptomatic non-treatment seekers were identified as impatient.
      Women seeking help for LUTS were identified as impatient, restless, authoritative
      and determined individuals. Asymptomatic women were identified as sensitive
      individuals who have strong ideals and desire their own way. Further studies are
      required to improve knowledge about the influence of personality on treatment
      seeking behaviour in women with LUTS.

PMID- 19603320
TI  - Waiting time to conception among the Igbo women of Enugu, Nigeria.
AB  - The objective of this study was to determine the waiting time to conception among
      a sample of pregnant Igbo women resident in an urban area of South-east Nigeria.
      This was a cross-sectional questionnaire study of antenatal clinic attendees at
      four major health institutions within Enugu, South-eastern Nigeria. The time to
      conception showed a pattern closer to that of the USA than that of the UK and is
      consistent with high fertility previously recorded in the Igbo population. We
      conclude that the data will be useful in counselling women who present with
      difficulty in conception.

PMID- 19603321
TI  - Knowledge, attitude and practice of private medical practitioners towards
      abortion and post abortion care in Enugu, South-eastern Nigeria.
AB  - The objective of this study was to determine the knowledge, attitude and practice
      of private medical practitioners in Enugu, South-eastern Nigeria, on abortion and
      post-abortion care. It was a cross-sectional study of private medical
      practitioners in the study area using self-administered structured
      questionnaires. The results showed that 32.3% of the doctors terminate unwanted
      pregnancies when requested to do so. The majority of them (51.6%) use D&C in
      combination with manual vacuum aspiration for the termination of pregnancies in
      the first trimester. A total of 61 (63.5%) respondents offered various types of
      post-abortal care (PAC) services, while 42 (43.8%) of them screened women with
      abortion complications for sexually transmitted infections. For the doctors who
      do not terminate unwanted pregnancies, their main reasons were religious and
      moral considerations rather than obedience to the Nigerian abortion laws. We
      conclude that the majority of private medical practitioners in Enugu, South
      eastern Nigeria, do not terminate unwanted pregnancies because of their religious
      beliefs.

PMID- 19603322
TI  - NovaSure impedance controlled system for endometrial ablation: the experience of
      the first UK reference centre.
AB  - In this study we assessed the effectiveness of the NovaSure Impedance Controlled
      Endometrial Ablation System for the treatment of menorrhagia in pre-menopausal
      women. A total of 125 pre-menopausal women with menorrhagia, which was secondary
      to dysfunctional uterine bleeding and unresponsive to medical therapy, had
      endometrial ablation using the NovaSure system between June 2004 and October
      2005. A postal questionnaire was sent to all patients and the response rate was
      80% (110 patients). The clinical data were analysed in 105 case notes (84%). The
      mean age was 43.91 +/- 5.45 SD, and mean parity was 2.09 +/- 0.65. The median
      treatment time was 71.00 s, ranging between 45.00 and 105.00 s. Results from a
      period of 18 months demonstrated that the NovaSure system was effective in
      reducing excessive uterine blood loss in 90.5% of patients and there were no
      intraoperative adverse events reported. Some 87% of patients were satisfied with
      the procedure and 90% of patients would be happy to recommend the treatment. We
      conclude that the NovaSure system is effective and safe in the treatment of
      symptomatic menorrhagia.

PMID- 19603323
TI  - Does physiotherapy treatment improve the self-reported pain levels and quality of
      life of women with vulvodynia? A pilot study.
AB  - The study investigated whether a 3-month period of physiotherapy treatment
      improved the pain levels and quality of life of women with vulvodynia. A quasi
      experimental method was used, comprising a within-subjects, pre-test/post-test
      design in which subjects acted as their own controls. A convenience sample of 14
      subjects was recruited from referrals to women's health physiotherapy between May
      and August 2004. The McGill Pain Questionnaire and Short Form 36 (version 2) were
      used to assess changes in self-reported pain levels and quality of life,
      respectively. Subjects completed questionnaires on recruitment to the study, 3
      months later (immediately prior to commencing physiotherapy treatment), and after
      3 months of treatment. The study investigated whether changes in pain levels and
      quality of life observed during the 3-month intervention phase differed from
      those observed during the 3-month control phase. The pain levels of study
      subjects reduced during the treatment period relative to the control period, and
      improvements were also observed in some aspects of quality of life. These results
      indicate that physiotherapy may offer some benefit in the treatment of
      vulvodynia. However, none of the findings reached statistical significance due to
      the small sample size. This study supports the view that physiotherapy provides
      pain relief for women with vulvodynia. Larger, randomised controlled trials are
      required to confirm the effectiveness of the treatment.

PMID- 19603324
TI  - An audit of standards of the 'see and treat' approach in women with a high-grade
      squamous intraepithelial lesion on Pap smears.
AB  - This study was undertaken to audit the performances of the 'see and treat'
      approach in women with a high-grade squamous intraepithelial lesion (HSIL)
      cytology at Chiang Mai University Hospital using selective criteria from the
      National Health Service Cervical Screening Programme (NHSCSP) 2004 guidelines.
      Women with a HSIL smear, who had undergone colposcopy and immediate loop
      electrosurgical excision procedure (LEEP) during June 2006 and September 2008,
      were reviewed. The standard measurement was determined by the following criteria:
      (1) the proportion of women treated at the first visit who have evidence of
      cervical intraepithelial neoplasia (CIN) on histology to be >90%; (2) the primary
      haemorrhage must be <5%; (3) the proportion of patients admitted as inpatients
      owing to treatment complication to be <2%. Of 247 women in this study, the
      histopathological results were as follows: CIN II-III, 188 (76.1%); cancer, 31
      (12.6%); adenocarcinoma in situ, 5 (2.0%); CIN I, 5 (2.0%); and no CIN, 18
      (7.3%). The prevalence of CIN I or higher was 92.7%. Primary haemorrhage was
      observed in 13 (5.3%) women. Four (1.6%) women were admitted as inpatients
      because of LEEP-related complications. In conclusion, the 'see and treat'
      approach in our institute has acceptable overtreatment and complication rates.

PMID- 19603325
TI  - Gestational trophoblastic neoplasia: are we compliant with the standards?
AB  - This study was conducted to assess the management of gestational trophoblastic
      diseases (GTN) in a district general hospital in accordance with the RCOG
      guidelines. A retrospective case notes review over a 5-year period found a total
      of 23 patients treated in this hospital. The annual incidence of hydatidiform
      mole was 1.3/1,000 deliveries (3,500 deliveries per annum). Ultrasound scanning
      diagnosed or suspected GTN in only nine of the 23 cases (39%); six women (26%)
      were diagnosed as missed miscarriage and another six (26%) were diagnosed as
      incomplete miscarriage. Eleven patients (48%) were not suspected before
      histological diagnosis. A total of 16 of the 23 cases (70%) were complete moles
      and the rest were partial moles; 19 of the 23 (83%) were referred to a specialist
      centre of which 60% were referred within 1 month. The rest were not documented.
      Contraceptive advice was documented only in 11 case notes (48%). Women with molar
      pregnancy should be referred to a specialist centre as early as possible and
      within 2-4 weeks of histological diagnosis, after appropriate counselling and
      contraceptive advice.

PMID- 19603326
TI  - Severe hyperemesis gravidarum on a background of gastroparesis.

PMID- 19603327
TI  - An unusual presentation of phaeochromocytoma as abdominal pain during pregnancy.

PMID- 19603328
TI  - Idiopathic thrombocytopaenic purpura in pregnancy presenting with life
      threatening epistaxis.

PMID- 19603329
TI  - Aplastic anaemia: uncomplicated pregnancy following allogeneic bone marrow
      transplantation.

PMID- 19603330
TI  - Fletcher factor deficiency in a woman requiring emergency caesarean section.

PMID- 19603331
TI  - Uterine rupture during the mid-trimester management of intrauterine fetal death.

PMID- 19603332
TI  - Colovaginal fistula: a rare long-term complication of polypropylene mesh
      sacrocolpopexy.

PMID- 19603333
TI  - Recognition and reduction of the impact of inheritable causes of ovarian failure.

PMID- 19603334
TI  - Ovarian hyperstimulation associated with spontaneous ectopic pregnancy.

PMID- 19603335
TI  - Spontaneous monochorionic monoamniotic twin tubal ectopic pregnancy.

PMID- 19603336
TI  - Ectopic pregnancy: a 1 in 1.4 x 10(8) patient.

PMID- 19603337
TI  - Neuroendocrine tumour of the ovary.

PMID- 19603338
TI  - Bladder tumour diagnosed in a case presenting with uterine leiomyoma and
      hydronephrosis.

PMID- 19603339
TI  - Primary peritoneal psammocarcinoma.

PMID- 19603342
TI  - An article and commentaries on the sexualization of girls.

PMID- 19603343
TI  - Relationships between intestinal parasitosis and handedness.
AB  - The aim of the study was to investigate if there is a possible relation between
      intestinal parasitosis and handedness in patients with suspected intestinal
      parasitosis. Hand preference was assessed on the Edinburgh Handedness Inventory.
      Stool samples were examined microscopically for the presence of parasite. In the
      present study right-handers had many more helminth infections and left-handers
      had many more protozoon infections. Lower rate of helminth infections in the
      present study, and higher asthma incidences in the left-handed population in
      literature, may be associated with different immune machinery in left-handed
      people than in right-handed ones.

PMID- 19603344
TI  - Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic
      stem cell transplantation.
AB  - Low CD34 + cell doses increase allograft-related mortality and very high doses
      increase the risk of graft-versus-host disease. The optimum CD34 + cell dose
      remains undefined. The effect of the CD34 + cell dose based on ideal weight was
      analyzed in 130 patients with hematologic malignancies undergoing reduced
      intensity allogeneic blood cell transplantation in the context of factors known
      to affect the outcome: chemosensitivity, donor age, lactate dehydrogenase (LDH),
      human leukocyte antigen (HLA) match, performance status, and platelet count. The
      survival of patients receiving >8 x 10(6)/kg CD34 + cells was not significantly
      different from those receiving <6. The outcome of those receiving 6-8 x 10(6)/kg
      CD34 + cells was significantly better than the rest. This superiority was
      confirmed in multivariable analysis. Among patients receiving <or=8 x 10(6)/kg
      CD34 + cells, an increasing number of infused cells was associated with higher
      overall survival in a continuous fashion (Risk ratio (RR) 0.8759; p = 0.045).
      Cell dose based on actual weight did not correlate with survival. The number of
      CD34 + cells infused, a potentially modifiable factor, affects survival after
      reduced-intensity allogeneic transplantation. We recommend a CD34 + cell dose of
      6-8 x 10(6) per kg ideal body weight to optimize outcome. The possible adverse
      effect of higher cell doses (>8) needs further confirmation.

PMID- 19603345
TI  - Advances in mobilization for the optimization of autologous stem cell
      transplantation.
AB  - In autologous stem cell transplantation, mobilized peripheral blood has replaced
      the bone marrow as the preferred source of hematopoietic stem cells (HSCs).
      Because HSCs normally exist in the blood in very low numbers, the use of agents
      to "mobilize" HSCs from the marrow niche to the peripheral blood is essential for
      successful transplantation. Until recently, granulocyte colony-stimulating factor
      (G-CSF) and granulocyte-macrophage colony-stimulating factor were the only
      approved agents by the US Food and Drug Administration for use as peripheral
      blood stem cell (PBSC)-mobilizing agents in the United States, but G-CSF has
      become the gold standard. Unfortunately, some patients fail to mobilize
      sufficient numbers of PBSCs for transplantation in response to G-CSF with or
      without chemotherapy. Recently, a new agent, plerixafor (AMD3100) added to G-CSF
      has been approved to enhance PBSC mobilization. This review will discuss the
      current methodologies to improve hematopoietic stem cell mobilization.

PMID- 19603346
TI  - Monitoring of minimal residual disease in patients with core binding factor acute
      myeloid leukemia and the impact of C-KIT, FLT3, and JAK2 mutations on clinical
      outcome.
AB  - Mutational analysis of C-KIT, fms-like tyrosine kinase 3 (FLT3), and JAK2 genes
      was performed in 60 patients with core binding factor acute myeloid leukemia (CBF
      AML). Patients reaching molecular remission had lower incidence of relapse and
      better overall survival (OS) than those not achieving molecular remission (p =
      0.008 and 0.044, respectively). The overall incidence of C-KIT mutations was
      33.3%, FLT3/internal tandem duplication (ITD) 6.6%, FLT3(D835) 10.0% and
      JAK2(V617F) mutations 3.3%. C-KIT mutations did not predict for
      clinical/molecular relapse (p = 0.33). OS of patients with C-KIT mutations was
      identical to patients without them when all patients with CBF-AML were analyzed
      together (p = 0.58). When AML1/ETO-positive patients were evaluated separately,
      OS in C-KIT-mutated patients was slightly inferior to unmutated ones (p = 0.14).
      Patients with CBF-AML with a mutated C-KIT gene were also more prone to
      extramedullary disease (p = 0.08). Of six patients harboring various FLT3(D835)
      mutations, four (66.7%) relapsed, whereas among 43 cases without these mutations,
      16 relapses (37%) were observed (p = 0.08). Our results on minimal residual
      disease, C-KIT, and FLT3/ITDs are in line with previous studies. Surprisingly, a
      possible role for FLT3(D835) mutations was noted in addition. These results need
      validation in even larger patient cohorts than ours. For routine clinical
      practice, it may be meaningful to screen for C-KIT mutations in AML1/ETO-positive
      patients, as well as for FLT3(D835) mutations in CBF-AML.

PMID- 19603347
TI  - Adult T-cell leukemia/lymphoma comprising non-floral leukemic cells in Taiwan, a
      country non-endemic for human T-cell leukemia virus type I.

PMID- 19603348
TI  - Gastric Burkitt lymphoma associated with Efalizumab and Helicobacter pylori.

PMID- 19603349
TI  - Concomitant EBV encoded RNA positive cutaneous nasal-type natural killer-cell
      lymphoma and EBV encoded RNA negative nasopharyngeal carcinoma.

PMID- 19603365
TI  - [Effect of whole body vibration exercise on osteoporotic risk factors].
AB  - BACKGROUND AND OBJECTIVE: Whole body vibration (WBV) training is a new approach
      which is currently discussed in the context of reducing the risk of osteoporotic
      fractures. The study was undertaken to determine the effect of one-year WBV
      exercise on bone mineral density (BMD) and the number of falls. METHODS: 151
      postmenopausal women (68.5 +/- 3.1 years) were randomly assigned to three groups:
      (1) conventional (multifunctional) training (TG); (2) multifunctional training
      including WBV (VTG); (3) wellness-control group (CG). The training groups
      performed multifunctional training twice weekly (60 min; dancing aerobics,
      balance training, functional strength training). In the last 15 min of each
      session, leg strength exercises on vibration platforms were performed. The plates
      were switched on only in the VTG. The CG performed a low intensity gymnastic and
      relaxation programme (4 x 10 sessions of 60 min). BMD was measured at the hip and
      lumbar spine at baseline and after 12 months with the DXA method. Falls were
      recorded daily with the calendar method in a fall log. RESULTS: An increase in
      BMD at the lumbar spine was measured after one year in both training groups (VTG:
      + 1.17 +/- 2.4 % vs. TG: + 1.73 +/- 2.4 %). The difference between the TG and the
      CG was significant (p < .05). Regarding the hip region a loss was noted in the CG
      (- 0.9 +/- 2.5), whereas the BMD stayed stable in the training groups (TG: - 0.3
      %; VTG: + 0.1 %). The fall rate was significantly lower in VTG compared to CG
      (0.43 falls/person/year (VTG) vs. 1.14 (CG). CONCLUSION: The multifunctional
      training resulted in a gain of BMD at the lumbar spine. Vibration training did
      not enhance the effect on bone but significantly reduced falls.

PMID- 19603366
TI  - [Acute exacerbation of a chronic esophagitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 50-year-old woman presented with progressive
      dysphagia and chest pain. Clinical and laboratory findings revealed a moderate
      epigastric pain and moderately elevated D-dimers. She had previously been
      diagnosed with esophagitis. Current oral medication included risedonate and
      clindamycin. INVESTIGATIONS: The electrocardiogram was appropriate for age, with
      a SIQIII-sign and sinus tachycardia. Echocardiography, abdominal sonography and
      chest X-ray were unremarkable. Gastroscopy demonstrated severe inflammatory
      lesions in the middle part of the esophagus. The biopsies revealed crystalline
      material microscopically. TREATMENT AND COURSE: The findings supported the
      diagnosis of an acute exacerbation of a chronic risedronat-induced esophagitis
      caused by clindamycin. After discontinuing the oral medication and giving
      intermittent parenteral nutrition the lesions healed completely. CONCLUSION: Drug
      induced esophagitis is often not recognized. Because of the high number of
      patients on bisphosphonate medication, often in combination with other
      potentially ulcerogenic drugs, the differential diagnosis should include drug
      induced esophagitis.

PMID- 19603367
TI  - [Fear of allowing sugar into the cell--case 05/2009. Comorbidity of diabetes
      mellitus and eating disorders].
AB  - HISTORY AND ADMISSION FINDINGS: An 19-year-old female patient was admitted to our
      department of psychosomatic medicine and psychotherapy for the treatment of her
      metabolically deranged type 1 diabetes mellitus. INVESTIGATIONS: Exploration and
      assessment revealed a typical eating disorder symptomatology. The body mass index
      at time of admission was 18.7 kg/m (2). Episodes of binge eating were followed by
      purging behaviour (insulin purging, vomiting). DIAGNOSIS, TREATMENT AND COURSE:
      After diagnosis of bulimia nervosa, the patient was treated with a structured
      dual treatment regime consisting of psychosomatic/psychotherapeutic interventions
      and endocrinological support. The existing complex bio-psycho-social conditions
      were considered carefully. In the treatment course typical eating disorder
      behaviour (i. e. insulin purging) decreased and mood stabilised. CONCLUSIONS:
      Adolescent women with diabetes mellitus are at an increased risk of developing an
      eating disorder. This comorbidity is associated with a markedly increased
      mortality. Therefore, diagnosis of an eating disorder should be made as soon as
      possible in order to provide adequate treatment not only for the metabolic
      disturbances but also for the coexisting psychosomatic disorder.

PMID- 19603368
TI  - [77-year-old man with conspicuous fingernail features].

PMID- 19603369
TI  - [Recent aspects of antibody determination for the diagnosis of coeliac disease].
AB  - Antibody assays play an important role in the diagnosis of coeliac disease
      (coeliac sprue, gluten-sensitive enteropathy), a condition characterized by
      immunological intolerance to gluten from wheat and from proteins of related
      cereals in genetically predisposed persons. Enhanced concentrations of IgA
      antibodies against tissue transglutaminase or endomysium under gluten-containing
      normal diet represent an important indication for a biopsy from the small
      intestine. Demonstration of typical changes in the mucose of the small intestine
      is still required for the definitive diagnosis of coeliac disease. Recently
      highly specific antibodies against deamidated gliadin peptides were detected in
      serum. These antibodies further improve the reliability of serologic diagnosis.
      The new assays for IgG-antibodies against deamidated gliadin peptides have a very
      high diagnostic accuracy and are comparable to IgA tissue transglutaminase
      antibodies. Further investigations have to show whether IgG-antibodies against
      deamidated gliadin peptides are a reliable disease marker also in case of IgA
      deficiency. Prospective studies are needed to show whether antibody assays could
      replace biopsy in the diagnosis of coeliac disease in a substantial number of
      patients.

PMID- 19603351
TI  - Fragment Bb in amniotic fluid: evidence for complement activation by the
      alternative pathway in women with intra-amniotic infection/inflammation.
AB  - OBJECTIVE: Fragment Bb is an activator of the alternative pathway of the
      complement system. Recently, increased first trimester maternal plasma
      concentrations of this fragment were reported in patients destined to have a
      spontaneous preterm delivery before 34 weeks of gestation. The aim of this study
      was to determine whether the amniotic fluid (AF) concentrations of fragment Bb
      change with gestational age, spontaneous labor (term and preterm) and in the
      presence of intra-amniotic infection/inflammation (IAI). STUDY DESIGN: This cross
      sectional study included patients in the following groups: (1) mid-trimester (n =
      64); (2) term in spontaneous labor (n = 70); (3) term not in labor (n = 43); (4)
      spontaneous preterm labor (PTL) who delivered at term (n = 76); (5) PTL without
      IAI who delivered preterm (n = 73); (6) PTL with IAI (n = 76); (7) preterm
      prelabor rupture of membranes (PROM) without IAI (n = 71); and (8) preterm PROM
      with IAI (n = 71). Fragment Bb concentration in AF was determined by an enzyme
      linked immunoassay. Non-parametric statistics were used for analyses. RESULTS:
      (1) Fragment Bb was detected in all AF samples (n = 544); (2) The median AF
      concentration of fragment Bb in patients at term not in labor was significantly
      higher than that of those in the mid-trimester [2.42 microg/ml, interquartile
      range (IQR) 1.78-3.22 vs. 1.64 microg/ml, IQR 1.06-3.49; p < 0.001]; (3) Among
      patients with PTL, those with IAI had a higher median AF fragment Bb
      concentration than that of woman without IAI, who delivered preterm (4.82
      microg/ml, IQR 3.32-6.08 vs. 3.67 microg/ml, IQR 2.35-4.57; p < 0.001) and than
      that of women with an episode of PTL, who delivered at term (3.21 microg/ml, IQR
      2.39-4.16; p < 0.001); (4) Similarly, among patients with preterm PROM, the
      median AF fragment Bb concentration was higher in individuals with IAI than in
      those without IAI (4.24 microg/ml, IQR 2.58-5.79 vs. 2.79 microg/ml, IQR 2.09
      3.89; p < 0.001). (5) Among patients at term, the median AF fragment Bb
      concentration did not differ between women with spontaneous labor and those
      without labor (term in labor: 2.47 microg/ml, IQR 1.86-3.22; p = 0.97).
      CONCLUSIONS: (1) Fragment Bb, an activator of the alternative complement pathway,
      is a physiologic constituent of the AF, and its concentration increases with
      advancing gestational age; (2) AF concentrations of fragment Bb are higher in
      pregnancies complicated with IAI; and (3) labor at term is not associated with
      changes in the AF concentrations of fragment Bb. These findings suggest a role
      for fragment Bb in the host immune response against IAI.

PMID- 19603370
TI  - [Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: good
      prognosis with early detection].
AB  - Neuroendocrine tumors (NET) of the stomach are on the rise. In the United States
      they have increased about tenfold in the last 35 years. Prognosis has been much
      improved over the last three to four decades. Nowadays most of such NETs are
      diagnosed at an early stage. Quite often gastric NETs are found incidentally
      during a gastroscopy, performed for other reasons. Most of the asymptomatic, well
      differentiated gastric NETs are less than 2 cm in diameter. Conservative
      management and endoscopic surveillance is adequate for well differentiated,
      multifocal type 1 or type 2 gastric NETs (gastric carcinoids) of 10-20 mm ,
      unless they are angio-invasive, have infiltrated into the muscularis propria or
      have metastasized. Endoscopic ultrasound is the method of choice to determine
      tumor size and depth of infiltration. Surgery is, however, indicated for all NETs
      larger than 20 mm. For optimal management tumor biology, type and stage of the
      neoplasm as well as the individual situation of the patient have to be taken into
      account. Most of the patients can be treated conservatively and be followed up
      with endoscopic surveillance.

PMID- 19603371
TI  - [Upright tilt-table test].

PMID- 19603372
TI  - [The "swine flu" influenza A/H1N1 - pandemia on trial].

PMID- 19603373
TI  - [Medical studies today: patient actors and "hammer examination"].

PMID- 19603374
TI  - [Replace the testing of minimal inhibitory concentration with resistance
      testing?].

PMID- 19603375
TI  - [Different indications of photodynamic therapy in ophthalmology].
AB  - BACKGROUND: Photodynamic therapy (PDT) in eye disease was approved 10 years ago
      for age-related macular degeneration (AMD). Thereafter it was approved for
      choroidal neovascularisation (CNV) in pathological myopia. The treatment regimen
      is based on two prospective, multicentre trials (TAP and VIP studies). MATERIAL
      AND METHODS: In the meantime PDT has been successfully used also in several other
      ocular diseases. PDT is minimally invasive and has an excellent side effect
      profile. Different diseases and their treatment with PDT are discussed. RESULTS:
      The treatments of idiopathic CNV, secondary CNV in inflammatory diseases of the
      retina and choroid, choroidal haemangioma, vasoproliferative tumours, malignant
      melanoma of the choroid, and central serous chorioretinopathy with PDT are
      described. In most patients the disease progression can be stopped and in some
      the PDT treatment results in visual improvement. The prognosis is better in
      patients with early disease detection and small lesions. CONCLUSION: Several
      retinal and choroidal diseases can be treated successfully with PDT. Except for
      AMD and pathological myopia, PDT is an off label treatment.

PMID- 19603376
TI  - [Cataract extraction and blue light--impact on the retina].
AB  - This review focuses on the scientific background for the use of "yellow
      artificial lenses". We will address the fact that numerous basic scientific
      publications point to a rationale for this practice although it is often
      difficult to derive clear-cut evidence from clinical epidemiological studies for
      the preventive use of yellow artificial lenses. In the first part we refer to
      studies showing that especially the shortwave part of the visible spectrum of
      light can be harmful for the retina and optic nerve. For this, we have screened
      the literature for the major sources of radical production and for the targets of
      oxidative stress after impingement of "blue light" on the retina. Furthermore, we
      can show that many studies in cell and molecular biology, animal experiments and
      first clinical trials point to a preferential use of yellow-tinted lenses
      especially in the elderly and AMD patients.

PMID- 19603377
TI  - [Retinal image quality pre- and post-lasik as a function of illuminance].
AB  - BACKGROUND: The aim of this study was to simulate the effect of illuminance on
      retinal image quality before and after LASIK. PATIENTS AND METHODS: Wavefront
      sensing was performed in eighteen eyes of 12 patients before and one month after
      uncomplicated LASIK using a Hartmann-Shack sensor. A sigmoid curve was fitted to
      pupillometry data obtained at 4, 0.4 and 0.04 lux. Based on the sigmoid fit, pre-
      and postoperative wavefront errors were simulated for different pupil diameters
      over a corresponding range from 10 (-2) to 10 (2) lux. Retinal image quality was
      described by computation of the visual Strehl ratio based on the optical transfer
      function (VSOTF) for a spectacle correction preoperatively and for the
      uncorrected eye postoperatively. RESULTS: At an illuminance of 1 lux the mean
      pupil diameter was 4.81 +/- 0.91 mm and log VSOTF dropped from -0.47 +/- 0.29 to 
      1.18 +/- 0.32 (p < 0.001) after LASIK. The steepest pupil-induced decrease of
      VSOTF occurred preoperatively at 0.67 +/- 0.26 lux (range 0.2 - 1.58 lux). After
      LASIK, L (crit) on average was 0.96 +/- 0.53 lux (p < 0.05; range 0.2 - 1.78).
      CONCLUSIONS: The steepest pupil-induced decrease of retinal image quality
      occurred in the high mesopic range, however, there was intersubject variability.

PMID- 19603379
TI  - [Patient satisfaction--a potential cornerstone of hospital management].
AB  - BACKGROUND: Hospitals consider themselves to be exposed to intense competition
      for patient admissions. Yet their competitive performance is only rarely assessed
      in terms of patient satisfaction. METHODS: Following agreed guidelines,
      formulated on the basis of interdisciplinary research, the University Clinical
      Centre (2,500 beds, 10,000 employees) of Schleswig Holstein, Germany's most
      northerly Bundesland, developed and distributed standardized questionnaires on
      patient satisfaction and collected them after completion. RESULTS: 18,711
      completed questionnaires were collected from a population of 71,000 treated
      patients (rate of return: 26%; males 50,6%; females 49,4%). Two-thirds of
      admissions were elective whereas the remainder were emergencies. The quarterly
      evaluation revealed quality of food and cleanliness as the main areas of
      complaint. Patients' dissatisfactions was the greater the longer the stay in
      hospital. Other differences between patients on statutory or private health
      insurance, respectively, were voiced regarding "respectful treatment" and
      "professional ability" (especially by private patients). Furthermore, patient
      satisfaction related to the duration of doctors' rotation (i.e. how long they
      were on duty), satisfaction being greater the longer the period of rotation.
      CONCLUSION: The study has provided information on patient satisfaction as a
      measure of effective hospital management.

PMID- 19603378
TI  - [Value of radical oncological surgery in bilateral synchronous renal cell cancer
      and coincidental simultaneous prostate cancer].
AB  - To date, the current literature does not report on oncological surgery in
      bilateral renal cell cancer and coincidental simultaneous prostate cancer. We
      present the case of a 66-year-old patient presenting as a challenge due to this
      oncological-surgical constellation. Based on the present case study and the
      postoperative follow-up, we discuss possible surgical strategies and demonstrate
      that, even in the case of multiple tumour locations, a satisfying oncological and
      functional long-term result is achievable.

PMID- 19603380
TI  - [Kallmann syndrome--a form of hypogonadotropic hypogonadism].
AB  - HISTORY: Two men (aged 44 and 47 years) were admitted with the diagnosis of
      Kallmann's syndrome, but they had widely different symptoms. The first patient
      (A) suffered from significant secondary symptoms, i.e. weight gain and skeletal
      pain, which had caused him to seek medical assistance. The second patient (B) had
      been admitted because of symptoms of depression, caused by separation from his
      female partner. INVESTIGATION: Patient A showed major somatic symptoms
      characteristic of the syndrome: eunuchoidism (physique, boyish voice,
      gynecomastia, micropenis and absent secondary sex characteristics). Further
      diagnostic tests revealed low testosterone concentrations (0.958 ng/ml; reference
      range 1.8 - 7.58 ng/ml) and low luteinizing hormone (LH) concentrations (<0.7
      IU/l; reference range 0.8 - 7.6 IU/l), as well as infertility. Radiology showed
      marked osteoporosis, providing the indication for total hip replacement. Magnetic
      resonance imaging (MRI) of the skull and chromosomal analysis gave normal
      results. The physical development of patient B had progressed ever since hormone
      substitution after a suspected diagnosis of mumps orchitis in early childhood.
      However infertility was still present. Abnormal laboratory findings at admission:
      LH 0.10 IU/l (reference range 0.8 - 7.6 IU/l), follicle stimulating hormone 0.10
      IU/l (reference range 1.2 - 10.1 IU/l), testosterone 10.0 ng/ml (reference range
      1.8 - 7.58 ng/ml). A hypoplastic olfactory sulcus was shown by MRI, but no
      olfactory bulb. Mineral density of the femur was slightly diminished. Combined
      stimulation test of the pituitary gland revealed hypogonadotropic hypogonadism
      and anosmia in both patients. TREATMENT AND COURSE: In patient A administration
      of testosterone, calcium, colecalciferol and biphosphonates improved virilization
      and reduced skeletal pain. Continuation of testosterone, calcium and
      colecalciferol treatment, psychotherapy and antidepressive medication with
      paroxetine were initiated in patient B. His symptoms of depression were treated
      successfully, but personal and sexual relationships remained difficult and had
      many problems. CONCLUSION: Early diagnosis of Kallmann's syndrome and symptomatic
      treatment with hormone replacement prevent patients from developing pernicious
      sequelae. However, sexual identity will be difficult even for patients treated
      after early diagnosis.

PMID- 19603381
TI  - [67-year-old patient with abdominal pain and pronounced peritonitis].

PMID- 19603382
TI  - [Diagnosis and therapy of fibromyalgia syndrome].
AB  - The meaningfulness of the term fibromyalgia syndrome (FMS), possible diagnostic
      criteria, and the therapeutic procedure, were for a long time points of
      contention between different professional associations. In an interdisciplinary
      S3 guideline on the definition, pathophysiology, diagnosis and therapy of FMS, it
      has now been possible to work out a consensus that is accepted by all involved
      professional associations and patient representatives on the basis of the
      available evidence. The most important results for clinical practice are
      presented and discussed here using case examples. The number of FMS patients in
      Germany is estimated to lie at 1.6 million (2% of the population), and 80-90% of
      those affected are women. FMS is classified under the functional somatic
      syndromes of the diseases of the musculoskeletal system and of the connective
      tissue (ICD 10 M 79.7). Comorbidities with other functional somatic syndromes and
      mental disorders are frequent. The clinical diagnosis of an FMS can ensue both by
      examining the tender points and also based on symptoms. Basic therapy includes
      elucidation and psychoeducation, aerobic endurance training adapted to the
      individual performance capability, operant behavioural therapy, and as a drug
      based therapy option, amitriptyline 25-50mg/d (all level of evidence 1a). A
      graded therapeutic procedure which includes the patients in the decision-making
      is recommended.

PMID- 19603383
TI  - [Problems of adult sickle cell patients in Germany].

PMID- 19603384
TI  - Prenatal diagnosis of right aortic arch: associated findings, pregnancy outcome,
      and clinical significance of vascular rings.
AB  - OBJECTIVES: To analyze the characteristics and clinical implications of right
      aortic arch (RAA) detected in fetal life. METHODS: Retrospective study of all
      cases of RAA diagnosed prenatally in high-risk patients who underwent fetal
      echocardiography between 2000 and 2007. RESULTS: There were 48 RAA; 18 had
      vascular ring (Group 1), including 15 RAA with aberrant left subclavian artery
      and 3 double aortic arch, and 30 had not vascular ring (Group 2), all RAA with
      mirror-image branching. The prenatal diagnosis was confirmed in 94%. In Group 1
      most fetuses had normal heart (89%), and none had 22q11 deletion. There were 16
      live births and all infants but one are asymptomatic (mean follow-up of 31
      months). In Group 2 almost all fetuses had congenital heart defects (CHDs) (97%),
      and five were chromosomally abnormal (17%), including four 22q11 deleted. The 1
      year survival rate was 69%, which was significantly higher in Group 1 (89% vs
      57%, p < 0.05). CONCLUSIONS: RAA can be accurately diagnosed by fetal
      echocardiography. The outlook for these patients largely depends on the presence
      of associated defects, mainly CHDs, and their severity. If isolated, aortic arch
      anomalies are asymptomatic vascular variants in most cases. This information is
      important to assist parental counseling in pregnancy.

PMID- 19603386
TI  - Prenatal diagnosis of 46,XX testicular DSD. Molecular, cytogenetic, molecular
      cytogenetic, and ultrasonographic evaluation.

PMID- 19603385
TI  - Hyperbranched polyamidoamines containing beta-cyclodextrin for controlled release
      of chlorambucil.
AB  - This work is focused on the controlled drug release behavior of hyperbranched
      HPMA in the presence of beta-CD. Hence, three HPMA-beta-CDs and a pure HPMA were
      synthesized by Michael addition polymerization. As a model drug, CLB (an anti
      cancer drug) was loaded into them via a solution method for in vitro release
      studies. The DSC results indicate that the CLB/polymer interactions are at the
      molecular level. Loading CLB into these polymers results in an evident increase
      in their glass transition temperatures, and DeltaT(g) depends on the beta-CD
      content. The controlled-release experiments show that the presence of beta-CD can
      appropriately slow the release of CLB from HPMA-beta-CDs and adjust the ratio of
      CLB released in total drug loading.

PMID- 19603387
TI  - Preparation of a super-long two column chromatography system and its application
      in separating glycosylated puerarin.
AB  - Separation of Puerarin-7-O-glucoside from its precursor, puerarin, using a common
      chromatography column packed with AB-8 macroporous resin was unsuccessful.
      Therefore, in this study a 8 m super-long flexible reinforced PVC column was
      externally added to the common column in order to improve the chromatography
      efficiency by increasing the number of theoretical plates. Both the PVC and
      common columns were separately packed with AB-8 macroporous resin slurry. The
      packed PVC column was coiled after washing and stored until use. The microbial
      transformation mixture with puerarin-7-O-glucoside and puerarin (250 mL) was
      loaded onto the common column, followed by washing with 2000 mL H(2)O. After
      attaching the coiled external PVC column to the common column, a linear gradient
      of 10-30% ethanol was applied to elute the target compound. Two peaks appeared:
      peak I contained puerarin-7-O-glucoside at 97.9% purity and 88.1% recovery rate,
      and peak II was puerarin at 98.7% purity and 87.0% recovery rate. The use of the
      coiled external flexible reinforced PVC column avoided spatial restriction for
      long columns, which made it much more convenient for column packing and
      chromatography operations. Furthermore, this method eliminated the resin blockage
      problem caused by stationary water pressure in a rigid vertical long column.
      Using an external super-long column, the PVC tube was connected with the common
      column only during elution, which avoided delay in time period during sample
      loading and column washes associated with the use of long external columns.

PMID- 19603388
TI  - Targeted optical injection of gold nanoparticles into single mammalian cells.
AB  - We present an all optical technique for the targeted delivery of single 100 nm
      diameter gold nanoparticles into a specified region of the interior of an
      individual mammalian cell through a combination of optical tweezing and optical
      injection. The internalisation of the nanoparticle is verified by confocal laser
      scanning microscopy and confocal laser scanning reflectance microscopy. This
      represents the first time that nano sized particles have been tweezed and
      optically injected into mammalian cells using only light, and provides a novel
      methodology for internalising nanosphere based biosensors within specific
      intracellular regions of a mammalian cell.

PMID- 19603389
TI  - Fused-core, sub-2 microm packings, and monolithic HPLC columns: a comparative
      evaluation.
AB  - Three different HPLC column technologies (i.e., monolith, fused-core particles,
      and sub-2 microm particles) were evaluated, comparing van Deemter plots, speed of
      analysis, back pressure, and mobile phase consumption. Very high linear
      velocities (approximately 12 mm/s) were achieved with the monolithic column using
      modest pressure (110 bar) at the expense of high mobile phase consumption. The
      minimum plate height of the monolith was similar to that of a 3 microm-particle
      packed column (i.e., h = 8 microm), operated at optimal linear velocities; the
      monolithic column showed substantially lower mass transfer dependence, however.
      The 2.7 microm fused-core packing material yielded efficiencies closer to the sub
      2 microm material than to the 3 microm-particle packed column and could be
      operated at high flow rates. The fused-core column was able to achieve linear
      velocities similar to those attained on the sub-2 microm column, staying below
      620 bar instead of almost near 1030 bar required by the sub-2 microm material.
      The lack of pH stability of the monolithic column prevented its use to separate
      basic compounds (i.e., tricyclic antidepressants) at high pH. Best separation of
      these components at high pH was achieved using the column packed with 1.7 microm
      hybrid material.

PMID- 19603391
TI  - Synthetic polycation: polynucleotide interactions determined using liquid
      chromatography with short monolithic columns.
AB  - LC on short monolithic columns (Convective Interaction Medium Disks) was applied
      to investigate several specially synthesized water soluble polycations of
      different charge type (primary, tertiary, quaternary amine), as well as a
      copolymer of neutral saccharide and cationic monomers, regarding their ability to
      form reversible complexes with DNA. For this purpose, two separation modes were
      used, namely, pseudo-affinity and cation-exchange chromatography. Synthetic
      polynucleotides, namely, polyriboadenylic acid (poly(rA)) and polyribocytidylic
      acid (poly(rC)), were used as approximate structural analogues of DNA. In first
      case, the hypothetical specific binding between dissolved polymers and
      polynucleotide (poly(rA) or poly(rC)), covalently attached to epoxy-bearing
      monolithic sorbent, has been studied and compared to the results obtained using
      cation exchange chromatography. Quantitative parameters of interactions between
      macromolecules were established using frontal elution method.

PMID- 19603390
TI  - Interpretive optimisation of organic solvent content and flow-rate in the
      separation of beta-blockers with a Chromolith RP-18e column.
AB  - The chromatographic performance of a Chromolith RP-18e column was comprehensively
      examined for a group of basic drugs (beta-blockers), eluted with isocratic ACN
      water mixtures at increasing flow-rate up to 6 mL/min. As the flow-rate increases
      at fixed mobile phase composition, peak distribution (selectivity) is maintained,
      but the relative peak widths increase. This reduces the resolution below
      satisfactory values for closely eluting compounds. With the monolithic column,
      flow-rate becomes thus an important factor to be optimised, in addition to the
      mobile phase composition. Since, theoretically, retention factors (k) are
      independent of the flow-rate, the classical quadratic model relating log k with
      the solvent content allows the prediction of the retention at any combination of
      organic solvent content and flow-rate. The small deviations found for the most
      retained compounds were corrected by including, in the quadratic model, an
      additional term correlating linearly log k with the flow-rate. Peak shape and
      resolution changes were predicted by taking advantage of the approximated linear
      relationships between peak half-widths and retention times, which offered similar
      coefficients for peaks eluting at different organic solvent contents and flow
      rates. The accuracy of the predictions in critical conditions was experimentally
      verified to be satisfactory.

PMID- 19603392
TI  - Hydrosilylated allyl-silica hybrid monolithic columns.
AB  - Organic-inorganic silica hybrid monolithic columns were synthesized containing an
      allyl pendant. The ally-monolithic columns were then modified via hydrosilylation
      reactions to introduce further surface functionalization. The approach was
      demonstrated by functionalizing allyl-monolytic columns with n-octyl
      dimethylsilane (C(8)-DMS) and benzyl-dimethylsilane (benzyl-DMS). Of the surface
      available ally groups on the hybrid monolith (i.e., 6.79 micromol/m(2)), 31.3%
      reacted via hydrosilylation, resulting in a C(8) surface coverage of 2.12
      micromol/m(2). When using benzyl-DMS, a surface coverage of 1.95 micromol/m(2)
      was calculated for the benzyl groups. The retentivity of the hybrid monolithic
      columns increased considerably after the hydrosilylation, as monitored by CLC and
      CEC. The largest increase in retention was observed with the C(8) modified
      monolith. The hybrid monolithic columns showed higher hydrolytic stability than
      monolithic columns prepared by the conventional silanoxane bonding of alkyl
      chlorosilanes modification. The ally-monolithic column provides a platform for
      the fabrication of hybrid monoliths that can be conveniently modified by means of
      hydrosilylation, tailoring the surface of the material. The approach is a
      promising method to prepare hybrid monolithic columns with versatile stationary
      phases in a simple and efficient manner.

PMID- 19603393
TI  - Application of monolithic columns in pharmaceutical analysis. Determination of
      indomethacin and its degradation products.
AB  - Comparison of HPLC methods using conventional particle-based and monolithic
      columns for determination of indomethacin and its two degradation products, viz.
      5-methoxy-2-methylindoleacetic acid and 4-chlorobenzoic acid, was carried out.
      Ketoprofen was used as an internal standard for data evaluation throughout the
      study. Conventional separation was based on analytical column Zorbax SB-Phenyl
      (75x4.6 mm; 3.5 microm particles) used with a mobile phase composition of
      acetonitrile and phosphoric acid 0.2% (50:50, v/v) and isocratic flow at 0.6
      mL/min. Three different lengths of Chromolith columns RP-18e (25x4.6 mm, 50x4.6
      mm, and 100x3 mm) were tested with respect to the validation parameters peak
      asymmetry, resolution, height equivalent to a theoretical plate, repeatability,
      and after optimisation compared to values obtained using a conventional Zorbax
      column. The developed methods were used to determine all three compounds in a
      pharmaceutical formulation--Indobene gel. Chromatographic parameters were
      comparable to those of a conventional particle-based column. The analysis time
      was shortened as expected (retention times were lowered by a factor of two).
      Moreover, the repeatability of peak areas and retention times obtained with a 50
      mm monolithic column was greatly improved (RSD values were lower than 0.40%).

PMID- 19603394
TI  - Versatility of polymethacrylate monoliths for chromatographic purification of
      biomolecules.
AB  - Polymethacrylate monoliths, specifically poly(glycidyl methacrylate-co-ethylene
      dimethacrylate) or poly(GMA-co-EDMA) monoliths, are a new generation of
      chromatographic supports and are significantly different from conventional
      particle-based adsorbents, membranes, and other monolithic supports for
      biomolecule purification. Similar to other monoliths, polymethacrylate monoliths
      possess large pores which allow convective flow of mobile phase and result in
      high flow rates at reduced pressure drop, unlike particulate supports. The
      simplicity of the adsorbent synthesis, pH resistance, and the ease and
      flexibility of tailoring their pore size to that of the target biomolecule are
      the key properties which differentiate polymethacrylate monoliths from other
      monoliths. Polymethacrylate monoliths are endowed with reactive epoxy groups for
      easy functionalization (with anion-exchange, hydrophobic, and affinity ligands)
      and high ligand retention. In this review, the structure and performance of
      polymethacrylate monoliths for chromatographic purification of biomolecules are
      evaluated and compared to those of other supports. The development and use of
      polymethacrylate monoliths for research applications have grown rapidly in recent
      times and have enabled the achievement of high through-put biomolecule
      purification on semi-preparative and preparative scales.

PMID- 19603395
TI  - New tricyclic and tetracyclic pyranocoumarins with an unprecedented C-4
      substituent. Structure elucidation of tamanolide, tamanolide D and tamanolide P
      from Calophyllum inophyllum of French Polynesia.
AB  - Three new pyranocoumarin derivatives, tamanolide (1), tamanolide D (2) and
      tamanolide P (3), were isolated from the almond seeds of Calophyllum inophyllum
      L. (Clusiaceae) grown in French Polynesia. These compounds, having an
      unprecedented C-4 isobutyl substituent, have been characterized as a new class of
      pyranocoumarins called tamanolides. Their structures were elucidated on the basis
      of 1D and 2D NMR techniques (COSY, NOESY, HSQC and HMBC) in association with MS
      (HR-ESI-MS) data analysis.

PMID- 19603396
TI  - Recent European Food Safety Authority toxicological evaluations of major
      phthalates used in food contact materials.
AB  - During the 1980s and 1990s, and at the EU level, the Scientific Committee for
      Food evaluated a number of phthalates that were being used, or were requested for
      use, as additives in plastics. At this time, peroxisome proliferation was
      considered as the pivotal effect on which toxicological evaluation of these
      chemicals was based. At the end of 1990s, a general consensus has been agreed
      that rodents are highly sensitive to the phenomenon of peroxisome proliferation
      and that this particular effect should not be used for human risk assessment.
      Consequently in 2004, it was requested from the newly created European Food
      Safety Authority to perform a new evaluation of the mainly used phthalates on the
      basis of existing data. This paper summarizes evaluations of
      butylbenzylphthalate, dibutylphthalate, diethylhexylphthalate.

PMID- 19603398
TI  - Antigen presenting cells and T cell interactions in the gastrointestinal tract.
AB  - Dendritic cells make up less than 1% of the cells in lymph nodes and tissues, but
      they are critical in initiating and directing T cell immune responses. In the
      gut, with exposure to myriad food and bacterial antigens, they probably control T
      cell unresponsiveness to food antigens and T cell hypersensitivity in disease
      situations. The need for the immune system to 'know' gut luminal antigens is
      demonstrated by the fact that dendritic cells send processes through the
      epithelium and directly sample antigens in the gut lumen. We present evidence
      that type I INF made by plasmacytoid dendritic cells may be important in coeliac
      disease.

PMID- 19603397
TI  - Immunostimulatory properties of coffee mannans.
AB  - Coffee infusion mannans are acetylated polysaccharides containing single Galp and
      Araf residues as side chains of a beta-(1 --> 4)-Manp backbone. These mannans are
      structurally similar to the bioactive acetylated mannans from Aloe vera (AV). In
      this study, acetylated mannans were obtained from two coffee infusions prepared
      from light and dark roasted beans. These samples were tested for their
      immunostimulatory activity and compared with an extract of AV mannan and with
      locust bean gum (LBG) galactomannans. The coffee samples, as well as the AV
      extract, stimulated murine B- and T-lymphocytes, as evaluated by the in vitro
      expression of the surface lymphocyte activation marker CD69, more marked on B-
      than on T-lymphocytes. In coffee samples, contrarily to the AV, no proliferative
      effect was noticed. LBG sample did not show any immunostimulatory activity.
      Because the material that remains in the residue of the hot water extraction was
      still very rich in mannans, a sequential extraction was performed and a main
      fraction was recovered with a 4 M NaOH solution. Because this material was
      insoluble in water, a partial acetylation was performed. These polysaccharides
      also showed immunostimulatory activity, opening the possibility of exploitation
      of coffee infusion and coffee residue as sources of bioactive polysaccharides.

PMID- 19603399
TI  - In vitro digestion methods for assessing the effect of food structure on allergen
      breakdown.
AB  - This article reviews the in vitro digestion models developed to assess the
      stability of food allergens during digestion. It is hypothesised that food
      allergens must exhibit sufficient gastro-intestinal stability to reach the
      intestinal mucosa where absorption and sensitisation (development of atopy) can
      occur. The investigation of stability of proteins within the gastrointestinal
      tract may provide prospective testing for allergenicity and could be a
      significant and valid parameter that distinguishes food allergens from
      nonallergens. Systematic evaluation of the stability of food allergens that are
      active via the gastrointestinal tract is currently tested in traditional pepsin
      digestibility models. The human gastrointestinal tract however is very complex
      and this article points out the importance of using physiologically relevant in
      vitro digestion systems for evaluating digestibility of allergens. This would
      involve the simulation of the stomach/small intestine environment (multi-phase
      models) with sequential addition of digestive enzymes, surfactants such as
      phospholipids and bile salts under physiological conditions, as well as the
      consideration of the effect of the food matrices on the allergen digestion.

PMID- 19603400
TI  - Effects of food processing on food allergens.
AB  - Food allergies are on the rise in Western countries. With the food allergen
      labeling requirements in the US and EU, there is an interest in learning how food
      processing affects food allergens. Numerous foods are processed in different ways
      at home, in institutional settings, and in industry. Depending on the processing
      method and the food, partial or complete removal of the offending allergen may be
      possible as illustrated by reduction of peanut allergen in vitro IgE
      immunoreactivity upon soaking and blanching treatments. When the allergen is
      discretely located in a food, one may physically separate and remove it from the
      food. For example, lye peeling has been reported to produce hypoallergenic peach
      nectar. Protein denaturation and/or hydrolysis during food processing can be used
      to produce hypoallergenic products. This paper provides a short overview of basic
      principles of food processing followed by examples of their effects on food
      allergen stability. Reviewed literature suggests assessment of processing effects
      on clinically relevant reactivity of food allergens is warranted.

PMID- 19603401
TI  - Utility of animal models for evaluating hypoallergenicity.
AB  - The goal of this article is to describe the use of in vitro methods as well as in
      vivo and ex vivo animal models to assess residual allergenicity of hypoallergenic
      (HA) foods, especially infant formulas. These animal models are also used for
      testing the oral tolerance-inducing capacities of infant formula; thus, they are
      very helpful in predicting allergenicity and the tolerogenic potential of HA
      infant formulas, and in helping to prevent adverse reactions in sensitive
      infants.

PMID- 19603402
TI  - Impact of food processing on the structural and allergenic properties of food
      allergens.
AB  - This article reviews recent studies that address one of the major unanswered
      questions in food allergy research: what attributes of food or food proteins
      contribute to or enhance food allergenicity?

PMID- 19603405
TI  - Dietary sources of lignans and isoflavones modulate responses to estradiol in
      estrogen reporter mice.
AB  - Dietary phytoestrogens, such as the lignan metabolite enterolactone (ENL) and the
      isoflavone genistein (GEN), are suggested to modulate the risk of estrogen
      dependent disease (e.g., breast cancer) through regulation of estrogen signaling.
      However, the effects of complex food items containing lignans or isoflavones on
      estrogen receptor (ER) transactivation have not been assessed so far. In this
      study, the modulation of ER-mediated signaling by dietary sources of lignans
      (cereals and flaxseed) and isoflavones (soy) was studied in vivo. Adult
      ovariectomized 3 x ERE-luciferase (luc) reporter mice received isocaloric diets
      supplemented with flaxseed, rye, wheat, or soy for 40 h or two weeks, and an
      additional group of mice was challenged with 17beta-estradiol (E(2)) following
      the two-week dietary intervention. In non-E(2)-treated mice, soy diet induced luc
      expression in liver, mammary gland, and pituitary gland while the other diets had
      no effects. Interestingly, all diets modulated the E(2)-induced luc expression.
      In particular rye diet efficiently reduced E(2)-induced luc expression as well as
      uterine growth, the hallmark of estrogen action in vivo. It is concluded that
      dietary sources of lignans and isoflavones can modulate estrogen signaling in
      vivo. The results suggest intriguing possibilities for the modulation of the risk
      of estrogen-dependent diseases by dietary means.

PMID- 19603403
TI  - NMR-based metabonomics reveals that plasma betaine increases upon intake of high
      fiber rye buns in hypercholesterolemic pigs.
AB  - This study presents an NMR-based metabonomic approach to explore the overall
      endogenous biochemical effects of a rye versus wheat-based fiber-rich diet in
      hypercholesterolemic pigs. The pigs were fed high-fat, high-cholesterol rye- (n =
      9) or wheat- (n = 8) based buns with similar levels of dietary fiber for 9-10 wk.
      Fasting plasma samples were collected 2 days before and after 8 and 12 days on
      the experimental diets, while postprandial samples taken after 58-67 days, and(
      1)H NMR spectra were acquired on these. Principal component analysis on the
      obtained NMR spectra demonstrated clear effects of diet on the plasma metabolite
      profile, and partial least squares regression discriminant analysis on the
      spectra revealed that the intensity of the spectral region at 3.29 ppm dominated
      the differentiation between the two diets, as the rye diet was associated with
      higher spectral intensity in this region. The 3.29 ppm signal is ascribed to
      N(CH(3))(3) protons in betaine, which may be an important contributor to the
      health promoting effects of rye.

PMID- 19603404
TI  - Protein hydrolysates from beta-conglycinin enriched soybean genotypes inhibit
      lipid accumulation and inflammation in vitro.
AB  - Obesity is a worldwide health concern and a well recognized predictor of
      premature mortality associated with a state of chronic inflammation. The
      objective was to evaluate the effect of soy protein hydrolysates (SPH) produced
      from different soybean genotypes by alcalase (SAH) or simulated gastrointestinal
      digestion (SGIH) on lipid accumulation in 3T3-L1 adipocytes. The anti
      inflammatory effect of SPH produced by alcalase on LPS-induced macrophage RAW
      264.7 cell line was also investigated. SAH (100 microM) derived from soybean
      enriched in beta-conglycinin (BC) (up to 47% total protein) decreased lipid
      accumulation (33-37% inhibition) through downregulation of gene expression of
      lipoprotein lipase (LPL) and fatty acid synthase (FAS). SGIH (100 microM)
      inhibited lipid accumulation to a lesser extent (8-14% inhibition) through
      inhibition of LPL gene expression. SAH (5 microM) decreased the production of
      nitric oxide (NO) (18-35%) and prostaglandin E(2) (PGE(2)) (47-71%) and the
      expression of inducible nitric oxide synthase (iNOS) (31-53%) and cycloxygenase-2
      (COX-2) (30-52%). This is the first investigation showing that soy hydrolysates
      inhibit LPS-induced iNOS/NO and COX-2/PGE(2 )pathways in macrophages. Soybeans
      enriched in BCs can provide hydrolysates that limit fat accumulation in fat cells
      and inflammatory pathways in vitro and therefore warrant further studies as a
      healthful food.

PMID- 19603406
TI  - Quantum chemistry investigation of electronic structure and NMR spectral
      characteristics for fluorides of dialkylamidosulfoxylic acids and related
      compounds.
AB  - The parent (H(2)N-S-F) and N,N-dialkyl-substituted fluorides of amidosulfoxylic
      acid (R(2)N-S-F, R=Me or R(2)N=Morph) as well as the related compounds X-S-F
      (X=CH(3), OH, F, SiH(3), PH(2), SH, Cl) have been investigated with quantum
      chemical calculations at the ab initio (MP2) level of approximation. The
      geometries, electronic structures, molecular orbital (MO) energies and NMR
      chemical shift values have been calculated to evaluate the role and extent of the
      polarization and delocalization effects in forming of the high-field fluorine NMR
      resonances within the series of interest. The deltaF magnitudes for all
      investigated fluorides of amidosulfoxylic acid as well as the deltaN value
      calculated for Me(2)N-S-F are in the good agreement with the (19)F and (14)N NMR
      chemical shift values measured experimentally. For the parent compounds, H(2)N-S
      F and H(2)N-SO(2)-F, the orientation of principal axes of the magnetic shielding
      tensors and the corresponding principal sigma(ii) values along these axes have
      been qualitatively interpreted basing on the analysis of the MO interactions in
      the presence of the rotating magnetic field.

PMID- 19603408
TI  - Addressing a systematic vibration artifact in diffusion-weighted MRI.
AB  - We have identified and studied a pronounced artifact in diffusion-weighted MRI on
      a clinical system. The artifact results from vibrations of the patient table due
      to low-frequency mechanical resonances of the system which are stimulated by the
      low-frequency gradient switching associated with the diffusion-weighting. The
      artifact manifests as localized signal-loss in images acquired with partial
      Fourier coverage when there is a strong component of the diffusion-gradient
      vector in the left-right direction. This signal loss is caused by local phase
      ramps in the image domain which shift the apparent k-space center for a
      particular voxel outside the covered region. The local signal loss masquerades as
      signal attenuation due to diffusion, severely disrupting the quantitative
      measures associated with diffusion-tensor imaging (DTI). We suggest a way to
      improve the interpretation of affected DTI data by including a co-regressor which
      accounts for the empirical response of regions affected by the artifact. We also
      demonstrate that the artifact may be avoided by acquiring full k-space data, and
      that subsequent increases in TE can be avoided by employing parallel
      acceleration.

PMID- 19603407
TI  - Metaanalytic connectivity modeling: delineating the functional connectivity of
      the human amygdala.
AB  - Functional neuroimaging has evolved into an indispensable tool for noninvasively
      investigating brain function. A recent development of such methodology is the
      creation of connectivity models for brain regions and related networks, efforts
      that have been inhibited by notable limitations. We present a new method for
      ascertaining functional connectivity of specific brain structures using
      metaanalytic connectivity modeling (MACM), along with validation of our method
      using a nonhuman primate database. Drawing from decades of neuroimaging research
      and spanning multiple behavioral domains, the method overcomes many weaknesses of
      conventional connectivity analyses and provides a simple, automated alternative
      to developing accurate and robust models of anatomically-defined human functional
      connectivity. Applying MACM to the amygdala, a small structure of the brain with
      a complex network of connections, we found high coherence with anatomical studies
      in nonhuman primates as well as human-based theoretical models of emotive
      cognitive integration, providing evidence for this novel method's utility.

PMID- 19603410
TI  - Pathological amygdala activation during working memory performance: Evidence for
      a pathophysiological trait marker in bipolar affective disorder.
AB  - Recent evidence suggests that deficits of working memory may be a promising
      neurocognitive endophenotype of bipolar affective disorder. However, little is
      known about the neurobiological correlates of these deficits. The aim of this
      study was to determine possible pathophysiological trait markers of bipolar
      disorder in neural circuits involved in working memory. Functional magnetic
      resonance imaging was performed in 18 euthymic bipolar patients and 18 matched
      healthy volunteers using two circuit-specific experimental tasks established by
      prior systematic neuroimaging studies of working memory. Both euthymic bipolar
      patients and healthy controls showed working memory-related brain activations
      that were highly consistent with findings from previous comparable neuroimaging
      studies in healthy subjects. While these patterns of brain activation were
      completely preserved in the bipolar patients, only the patients exhibited
      activation of the right amygdala during the articulatory rehearsal task. In the
      same task, functional activation in right frontal and intraparietal cortex and in
      the right cerebellum was significantly enhanced in the patients. These findings
      indicate that the right amygdala is pathologically activated in euthymic bipolar
      patients during performance of a circuit-specific working memory task
      (articulatory rehearsal). This pathophysiological abnormality appears to be a
      trait marker in bipolar disorders that can be observed even in the euthymic state
      and that seems to be largely independent of task performance and medication.

PMID- 19603409
TI  - Optimal diffusion MRI acquisition for fiber orientation density estimation: an
      analytic approach.
AB  - An important challenge in the design of diffusion MRI experiments is how to
      optimize statistical efficiency, i.e., the accuracy with which parameters can be
      estimated from the diffusion data in a given amount of imaging time. In model
      based spherical deconvolution analysis, the quantity of interest is the fiber
      orientation density (FOD). Here, we demonstrate how the spherical harmonics (SH)
      can be used to form an explicit analytic expression for the efficiency of the
      minimum variance (maximally efficient) linear unbiased estimator of the FOD.
      Using this expression, we calculate optimal b-values for maximum FOD estimation
      efficiency with SH expansion orders of L = 2, 4, 6, and 8 to be approximately b =
      1,500, 3,000, 4,600, and 6,200 s/mm(2), respectively. However, the arrangement of
      diffusion directions and scanner-specific hardware limitations also play a role
      in determining the realizable efficiency of the FOD estimator that can be
      achieved in practice. We show how some commonly used methods for selecting
      diffusion directions are sometimes inefficient, and propose a new method for
      selecting diffusion directions in MRI based on maximizing the statistical
      efficiency. We further demonstrate how scanner-specific hardware limitations
      generally lead to optimal b-values that are slightly lower than the ideal b
      values. In summary, the analytic expression for the statistical efficiency of the
      unbiased FOD estimator provides important insight into the fundamental tradeoff
      between angular resolution, b-value, and FOD estimation accuracy.

PMID- 19603412
TI  - Ontogeny, variation, and homology in Salvelinus alpinus caudal skeleton
      (Teleostei: Salmonidae).
AB  - The ontogeny of the caudal skeleton in the Arctic charr, Salvelinus alpinus was
      examined using an extensive series of cleared and stained specimens. We
      demonstrate the presence of skeletal components never reported previously within
      the Salmonidae. In contrast to the generalized condition for salmonids, seven
      hypurals (instead of six), and four uroneurals (instead of three) have been found
      in some specimens. Variation in the number and condition of epurals is
      documented. New hypotheses are proposed concerning (1) relationships among centra
      and their associated elements, (2) phylogenetic distribution of caudal characters
      within the Salmonidae, and (3) homology of caudal components. Using the published
      phylogenetic hypotheses, we provide evidence, that a seventh hypural and a fourth
      uroneural are taxic atavism in salmonids. The development of the salmonid
      homocercal fin is discussed in the light of a polyural scheme based on evidences
      of a one-to-one relationship among ural centra and their associated elements.

PMID- 19603411
TI  - Cervids with different vocal behavior demonstrate different viscoelastic
      properties of their vocal folds.
AB  - The authors test the hypothesis that vocal fold morphology and biomechanical
      properties covary with species-specific vocal function. They investigate mule
      deer (Odocoileus hemionus) vocal folds, building on, and extending data on a
      related cervid, the Rocky Mountain elk (Cervus elaphus nelsoni). The mule deer,
      in contrast to the elk, is a species with relatively little vocal activity in
      adult animals. Mule deer and elk vocal folds show the typical three components of
      the mammalian vocal fold (epithelium, lamina propria and thyroarytenoid muscle).
      The vocal fold epithelium and the lamina propria were investigated in two sets of
      tensile tests. First, creep rupture tests demonstrated that ultimate stress in
      mule deer lamina propria is of the same magnitude as in elk. Second, cyclic
      loading tests revealed similar elastic moduli for the vocal fold epithelium in
      mule deer and elk. The elastic modulus of the lamina propria is also similar
      between the two species in the low-strain region, but differs at strains larger
      than 0.3. Sex differences in the stress-strain response, which have been reported
      for elk and human vocal folds, were not found for mule deer vocal folds. The
      laminae propriae in mule deer and elk vocal folds are comparatively large. In
      general, a thick and uniformly stiff lamina propria does not self-oscillate well,
      even when high subglottic pressure is applied. If the less stiff vocal fold seen
      in elk is associated with a differentiated lamina propria it would allow the
      vocal fold to vibrate at high tension and high subglottic pressure. The results
      of this study support the hypothesis that viscoelastic properties of vocal folds
      varies with function and vocal behavior.

PMID- 19603413
TI  - Degenerative and regenerative processes involved in midgut pseudotumor formation
      in the stick insect (Carausius morosus).
AB  - Spontaneous and experimentally induced pseudotumor formation in Carausius morosus
      impairs the midgut tissue homeostasis. Spontaneous pseudotumor formation begins
      by the break down of a single or a small group of columnar cells (CCs) and is
      followed by the degeneration of neighboring CCs. There are not only marked
      similarities but also decisive differences between normal dying CCs in healthy
      specimens and the degeneration of CCs leading to pseudotumors: in both cases, the
      apical cell parts with the nucleus are extruded into the midgut lumen, but only
      during of pseudotumor formation an "amorphous substance" originates from the
      basal parts of the CCs. Hemocytes are attracted to this substance and form a
      nodule-like aggregation, which is responsible for the phenotype of pseudotumors.
      Pseudotumor infestation has also an impact on the midgut nidi, which consist of
      an intestinal stem cell and several CC progenitor cells. In healthy specimens
      only one progenitor cell per nidus differentiates at a time, but, several to all
      progenitor cells differentiate simultaneously in pseudotumor-infested specimens.
      Extirpation of the ingluvial ganglion in healthy specimens results in an
      immediate onset of pseudotumor formation and a dramatic acceleration of
      pseudotumor growth. Importantly, the ultrastructural characteristics of
      spontaneous and experimentally induced pseudotumors are identical. This supports
      the idea that the stomatogastric nervous system plays an integral role in the
      maintenance of midgut tissue homeostasis.

PMID- 19603414
TI  - Osteology of the Graveldiver Scytalina cerdale (Perciformes: Zoarcoidei:
      Scytalinidae).
AB  - The Graveldiver, Scytalina cerdale, is a small, poorly known burrowing fish from
      the intertidal and subtidal zones of the west coast of North America, ranging
      from south-central California to Alaska. This is the sole member of the family
      Scytalinidae, which is included in the Zoarcoidei. Although it was described over
      120 years ago, it is rare in natural history collections and its anatomy is only
      imperfectly known. This article describes and illustrates the skeletal anatomy of
      S. cerdale based on newly prepared cleared and stained specimens. Many points of
      its anatomy are clarified or corrected (e.g., presence of the intercalars and
      ribs, in contrast to their reported absence) or described for the first time
      (e.g., structure of its gill-arches). Previous hypotheses of its systematic
      placement within the Zoarcoidei are discussed. On the basis of preliminary
      comparisons, S. cerdale may have phylogenetic affinity with at least some members
      of the family Stichaeidae (e.g., Xiphister). However, further study is needed on
      the anatomy and inter-relationships of the families of the Zoarcoidei before any
      conclusions can be made.

PMID- 19603415
TI  - Effects of resveratrol analogs on steroidogenesis and mitochondrial function in
      rat Leydig cells in vitro.
AB  - Resveratrol and its analogs are considered to be a promising drug candidate for
      treatment of cancer and different age-associated diseases. In the present study
      we have investigated the effects of resveratrol and its synthetic analogs on
      steroidogenesis and mitochondrial function in primary cultures of rat Leydig
      cells. Our findings indicate that resveratrol and its analogs structure
      dependently attenuated hCG-activated steroidogenesis in Leydig cells through
      suppression of the expression of steroidogenic acute regulatory protein and
      cytochrome P450c17. 3,5-Diacetyl resveratrol was observed to modulate
      mitochondrial function in Leydig cells, suppressing polarization of inner
      mitochondrial membrane, and 3,4,4'-trimethoxystilbene stimulated the overall
      activity of intracellular reductases involved in the reduction of WST-1 to
      formazan. Thus, the inhibitory actions of resveratrol analogs on steroidogenesis
      in Leydig cells indicate novel mechanisms of action of these compounds, which may
      be of potential therapeutic interest, where suppression of androgen action is
      needed.

PMID- 19603417
TI  - Chimpanzee seed dispersal quantity in a tropical montane forest of Rwanda.
AB  - We describe chimpanzee seed dispersal in the tropical montane forest of Nyungwe
      National Park (NNP), Rwanda, for a total of three years from January 1998 through
      May 2000 and May 2006 through March 2007. Relatively few studies have examined
      chimpanzee seed dispersal in montane communities where there are generally fewer
      fruiting tree species than in lowland forests. Such studies may reveal new
      insights into chimpanzee seed dispersal behaviors and the role that they play in
      forest regeneration processes. Chimpanzees are large-bodied, highly frugivorous,
      and tend to deposit the seeds of both large- and small-seeded fruits they consume
      in a viable state. We found that chimpanzees dispersed a total of 37 fruiting
      species (20 families) in their feces, 35% of which were large-seeded trees (> or
      =0.5 cm). A single large-seeded tree, Syzygium guineense, was the only species to
      be dispersed in both wadges and feces. Based on phenological patterns of the top
      five large-seeded tree species found in chimpanzee feces, our results indicate
      that chimpanzees do not choose fruits based on their availability. There was,
      however, a positive relationship between the presence of Ekebergia capensis seeds
      in chimpanzee feces and S. guineense seeds in chimpanzee wadges and their
      respective fruit availabilities. Our data reveal that proportionately fewer
      chimpanzee fecal samples at NNP contained seeds than that reported in two other
      communities in the Albertine Rift including one at mid-elevation and one in
      montane forest. As in other chimpanzee communities, seeds of Ficus spp. were the
      most common genus in NNP chimpanzee feces. Our data do not support previous
      studies that describe Ficus spp. as a fallback food for chimpanzees and
      highlights an intriguing relationship between chimpanzees and the large-seeded
      tree species, S. guineense.

PMID- 19603416
TI  - Minireview: does in-vitro testing of oximes help predict their in-vivo action
      after paraoxon exposure?
AB  - K-oximes have recently been developed in the search for efficacious broad-band
      reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus
      compounds (OPC). Before clinical use, their toxicity and efficacy need to be
      assessed, and there is clear demand for simple in vitro tests that can predict in
      vivo performance. This article summarizes our in vitro data obtained for
      conventional and experimental oximes in human and rat blood exposed to the OPC
      paraoxon and correlates them with our in vivo results. The intrinsic AChE
      inhibitory activity of oximes, as reflected by their in vitro IC(50), is strongly
      correlated with their LD(50) (rat): oximes with a high IC(50) (K-27, K-48,
      pralidoxime and obidoxime) also show a high LD(50) and are thus relatively non
      toxic, whereas oximes K-105, K-108 and K-113 have a low IC(50), a low LD(50) and
      are far more toxic. The IC(50) is also correlated with the in vivo capacity to
      protect from paraoxon-induced mortality: oximes with a higher IC(50) reduce the
      relative risk of death more. In contrast, the protective ability as assessed in
      vitro by the slope of the IC(50) shift (tanalpha), is not correlated with in vivo
      protection from paraoxon-induced mortality: the best in vivo protectors (K-27 and
      K-48) show a much lower tanalpha value (around 2) than K-110 and K-113 (tanalpha
      around 10), which hardly reduce the relative risk of death after paraoxon
      exposure. The partition coefficient logP of the individual oximes is inversely
      correlated with their IC(50) and with their LD(50) and is therefore an indicator
      of toxicity: strongly hydrophilic oximes tend to be less toxic than less
      hydrophilic ones. These data highlight the good predictive value of in vitro
      IC(50) testing for in vivo toxicity and the limited practical significance of in
      vitro assessment of protective potency.

PMID- 19603420
TI  - Longitudinal investigation of wandering behavior in Department of Veterans
      Affairs nursing home care units.
AB  - OBJECTIVES: To explore the extent of and factors associated with male residents
      who change wandering status post nursing home admission. DESIGN: Longitudinal
      design with secondary data analyses. Admissions over a 4-year period were
      examined using repeat assessments with the Minimum Data Set (MDS) to formulate a
      model understanding the development of wandering behavior. SETTING: One hundred
      thirty-four Veterans Administration (VA) nursing homes throughout the United
      States. PARTICIPANTS: Included 6673 residents admitted to VA nursing homes
      between October 2000 and October 2004. MEASUREMENTS: MDS variables (cognitive
      impairment, mood, behavior problems, activities of daily living and wandering)
      included ratings recorded at residents' admission to the nursing home and a
      minimum of two other time points at quarterly intervals. RESULTS: The majority
      (86%) of the sample were classified as non-wanderers at admission and most of
      these (94%) remained non-wanderers until discharge or the end of the study. Fifty
      one per cent of the wanderers changed status to non-wanderers with 6% of these
      residents fluctuating in status more than two times. Admission variables
      associated with an increased risk of changing status from non-wandering to
      wandering included older age, greater cognitive impairment, more socially
      inappropriate behavior, resisting care, easier distractibility, and needing less
      help with personal hygiene. Requiring assistance with locomotion and having three
      or more medical comorbidities were associated with a decreased chance of changing
      from non-wandering to wandering status. CONCLUSION: A resident's change from non
      wandering to wandering status may reflect an undetected medical event that
      affects cognition, but spares mobility.

PMID- 19603421
TI  - Adenylosuccinate synthetase 1 gene is a novel target of deletion in lung
      adenocarcinoma.
AB  - Tobacco smoke consists of numerous carcinogens whose effect on lung tumor
      development includes the induction of mutations in key genes as well as the
      induction of chromosome instability (CIN). Consequently, carcinogen-induced mouse
      lung adenocarcinomas (LAC) display many more recurrent site- and chromosome
      specific changes in DNA copy number compared with noninduced LAC. Here we
      identified the Adenylosuccinate synthetase 1 (Adss1) gene located on distal
      chromosome 12q as a focus of bi-allelic or homozygous deletion (HD) in LAC. HDs
      of Adss1 were detected in 10 out of 84 carcinogen-induced mouse primary LAC and
      mouse LAC cell lines. In only four of these cases did the deletions affect either
      Siva1 or Inverted-formin 2 (Inf2), which immediately flank the Adss1 locus,
      indicating that Adss1 is a selective target of deletion in LAC. Losses of Adss1
      not meeting the quantitative threshold of HD were detected in 36 out of 84
      (42.9%) of the mouse tumors and cell lines. A similar frequency of ADSS1 deletion
      was observed in human LAC cell lines, suggesting relevance in human lung cancer.
      Adss1 losses were also found to be significantly associated with a more extensive
      CIN phenotype in the primary mouse tumors. These results implicate ADSS1
      inactivation as a novel somatic alteration in lung carcinogenesis, and suggest
      that its selective deletion in LAC may be triggered by CIN.

PMID- 19603419
TI  - Meta-analysis of brain-derived neurotrophic factor p.Val66Met in adult ADHD in
      four European populations.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a multifactorial,
      neurodevelopmental disorder that often persists into adolescence and adulthood
      and is characterized by inattention, hyperactivity and impulsiveness. Before the
      advent of the first genome-wide association studies in ADHD, genetic research had
      mainly focused on candidate genes related to the dopaminergic and serotoninergic
      systems, although several other genes had also been assessed. Pharmacological
      data, analysis of animal models and association studies suggest that Brain
      Derived Neurotrophic Factor (BDNF) is also a strong candidate gene for ADHD.
      Several polymorphisms in BDNF have been reported and studied in psychiatric
      disorders but the most frequent is the p.Val66Met (rs6265G > A) single nucleotide
      polymorphism (SNP), with functional effects on the intracellular trafficking and
      secretion of the protein. To deal with the inconsistency raised among different
      case-control and family-based association studies regarding the p.Val66Met
      contribution to ADHD, we performed a meta-analysis of published as well as
      unpublished data from four different centers that are part of the International
      Multicentre Persistent ADHD CollaboraTion (IMpACT). A total of 1,445 adulthood
      ADHD patients and 2,247 sex-matched controls were available for the study. No
      association between the p.Val66Met polymorphism and ADHD was found in any of the
      four populations or in the pooled sample. The meta-analysis also showed that the
      overall gene effect for ADHD was not statistically significant when gender or
      comorbidity with mood disorders were considered. Despite the potential role of
      BDNF in ADHD, our data do not support the involvement of p.Val66Met in the
      pathogenesis of this neuropsychiatric disorder.

PMID- 19603422
TI  - PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in
      pancreatic cancer cells.
AB  - Phosphatidylinositol 3-kinase (PI3K) signaling controls survival and
      proliferation of cancer cells and is activated in around 60% of pancreatic ductal
      adenocarcinomas (PDACs). Although not entirely clarified, PI3K signaling is
      linked to cell cycle progression of PDAC cells. In this study we demonstrate that
      PI3K signaling controls transcription of the E2F1 gene and show that E2F1 is
      essential for S-phase progression of PDAC cells. On the molecular level, PI3K
      signaling controls c-myc protein abundance in a glycogen synthase kinase-3 (GSK3)
      dependent fashion. c-myc binds to the E-box of the E2F1 gene in PDAC cells and
      this binding is under control of the PI3K-signaling pathway. Together, we
      demonstrate that PI3K-GSK3-dependent control of c-myc protein expression is
      connected to the transcription of the E2F1 gene in PDAC cells, leading to S-phase
      progression of the cell cycle.

PMID- 19603423
TI  - Suggestive evidence for linkage of ADHD features in bipolar disorder to
      chromosome 10p14.
AB  - Higher rates of bipolar disorder amongst the first-degree relatives of probands
      with ADHD, and increased rates of ADHD in the relatives of bipolar probands have
      been reported in many studies. This suggests some commonality in the genetic
      basis for bipolar disorder and ADHD. We hypothesized that ADHD symptoms in
      bipolar disorder may access a quantitative subphenotype that is genetically less
      complex and therefore advantageous for mapping studies. The Wender Utah Rating
      Scale (WURS) was used to quantify ADHD features in 57 bipolar families collected
      for linkage studies. The factor structure of the WURS was first examined, and
      heritability was estimated. Linkage analysis was then conducted using the WURS
      total score and factor scores as quantitative traits. Three factors were
      identified: impulsivity and defiant behavior, mood instability and anxiety, and
      inattention. The total WURS and factor scores were each significantly heritable
      (0.34 <h(2r) < 0.49) in bipolar families. The inattention factor obtained maximum
      evidence of linkage on chromosome 10p14 (LOD = 3.35, 25 cM). A LOD score of 2.06
      for the total WURS score was found on chromosome 12q24 region. Childhood ADHD
      features in patients with bipolar disorder are heritable and may represent a
      genetically distinct dimension of illness. 10p14, in particular may contain a
      locus for inattention in bipolar disorder. Quantitative dimensional phenotypes
      such as this may be useful for both mapping of genes and understanding the role
      of genes in bipolar disorder.

PMID- 19603424
TI  - Micronization of lysozyme by supercritical assisted atomization.
AB  - Supercritical Assisted Atomization (SAA) has been used to produce lysozyme
      microparticles. Lysozyme has been micronized using water, buffered water at pH
      6.2 and water-ethanol mixtures at different volume percentages. Precipitated
      lysozyme particles were spherical, with a narrow particle size distribution (PSD)
      ranging from 0.1 to 4 microm. The concentration of lysozyme in the liquid solvent
      mixture had a nonlinear effect on the particle distribution, with an increase of
      the X(0.9) from about 1 to 3 microm varying the enzyme concentration from 5 to 20
      mg/mL. Precipitation temperature was set as low as possible to avoid enzyme
      degradation. High-performance liquid chromatography analysis showed no
      degradation of lysozyme and the enzyme activity, measured by turbidimetric
      enzymatic assay, only slightly decreased after SAA processing. Depending on the
      process conditions lysozyme retained from 95% to 100% of the biological activity
      compared to the untreated enzyme.

PMID- 19603425
TI  - Transmural flow bioreactor for vascular tissue engineering.
AB  - Nutrient transport limitation remains a fundamental issue for in vitro culture of
      engineered tissues. In this study, perfusion bioreactor configurations were
      investigated to provide uniform delivery of oxygen to media equivalents (MEs)
      being developed as the basis for tissue-engineered arteries. Bioreactor
      configurations were developed to evaluate oxygen delivery associated with
      complete transmural flow (through the wall of the ME), complete axial flow
      (through the lumen), and a combination of these flows. In addition, transport
      models of the different flow configurations were analyzed to determine the most
      uniform oxygen profile throughout the tissue, incorporating direct measurements
      of tissue hydraulic conductivity, cellular O(2) consumption kinetics, and cell
      density along with ME physical dimensions. Model results indicate that dissolved
      oxygen (DO) uniformity is improved when a combination of transmural and axial
      flow is implemented; however, detrimental effects could occur due to lumenal
      pressure exceeding the burst pressure or damaging interstitial shear stress
      imparted by excessive transmural flow rates or decreasing hydraulic conductivity
      due to ME compaction. The model was verified by comparing predicted with measured
      outlet DO concentrations. Based on these results, the combination of a controlled
      transmural flow coupled with axial flow presents an attractive means to increase
      the transport of nutrients to cells within the cultured tissue to improve growth
      (increased cell and extracellular matrix concentrations) as well as uniformity.

PMID- 19603427
TI  - Design and validation of a pulsatile perfusion bioreactor for 3D high cell
      density cultures.
AB  - This study presents the design and validation of a pulsatile flow perfusion
      bioreactor able to provide a suitable environment for 3D high cell density
      cultures for tissue engineering applications. Our bioreactor system is mobile,
      does not require the use of traditional cell culture incubators and is easy to
      sterilize. It provides real-time monitoring and stable control of pH, dissolved
      oxygen concentration, temperature, pressure, pulsation frequency, and flow rate.
      In this bioreactor system, cells are cultured in a gel within a chamber perfused
      by a culture medium fed by hollow fibers. Human umbilical vein endothelial cells
      (HUVEC) suspended in fibrin were found to be living, making connections and
      proliferating up to five to six times their initial seeding number after a 48-h
      culture period. Cells were uniformly dispersed within the 14.40 mm x 17.46 mm x
      6.35 mm chamber. A larger fraction of the cells suspended in 6.35-mm thick gels
      and cultured in a traditional CO(2) incubator were found to be round and dead
      [corrected]. In control experiments carried out in a traditional cell culture
      incubator, the scarcely found living cells were mostly on top of the gels, while
      cells cultured under perfusion bioreactor conditions were found to be alive and
      uniformly distributed across the gel.

PMID- 19603426
TI  - Controlled release of neurotrophin-3 from fibrin-based tissue engineering
      scaffolds enhances neural fiber sprouting following subacute spinal cord injury.
AB  - This study investigated whether delayed treatment of spinal cord injury with
      controlled release of neurotrophin-3 (NT-3) from fibrin scaffolds can stimulate
      enhanced neural fiber sprouting. Long Evans rats received a T9 dorsal hemisection
      spinal cord injury. Two weeks later, the injury site was re-exposed, and either a
      fibrin scaffold alone, a fibrin scaffold containing a heparin-based delivery
      system with different concentrations of NT-3 (500 and 1,000 ng/mL), or a fibrin
      scaffold containing 1,000 ng/mL of NT-3 (no delivery system) was implanted into
      the injury site. The injured spinal cords were evaluated for morphological
      differences using markers for neurons, astrocytes, and chondroitin sulfate
      proteoglycans 2 weeks after treatment. The addition of 500 ng/mL of NT-3 with the
      delivery system resulted in an increase in neural fiber density compared to
      fibrin alone. These results demonstrate that the controlled release of NT-3 from
      fibrin scaffolds can enhance neural fiber sprouting even when treatment is
      delayed 2 weeks following injury.

PMID- 19603428
TI  - Model identification in presence of incomplete information by generalized
      principal component analysis: application to the common and differential
      responses of Escherichia coli to multiple pulse perturbations in continuous, high
      biomass density culture.
AB  - In a previous report we described a multivariate approach to discriminate between
      the different response mechanisms operating in Escherichia coli when a steady,
      continuous culture of these bacteria was perturbed by a glycerol pulse (Guebel et
      al., 2009, Biotechnol Bioeng 102: 910-922). Herein, we present a procedure to
      extend this analysis when multiple, spaced pulse perturbations (glycerol,
      fumarate, acetate, crotonobetaine, hypersaline plus high-glycerol basal medium
      and crotonobetaine plus hypersaline basal medium) are being assessed. The
      proposed method allows us to identify not only the common responses among
      different perturbation conditions, but to recognize the specific response for a
      given stimulus even when the dynamics of the perturbation is unknown. Components
      common to all conditions are determined first by Generalized Principal Components
      Analysis (GPCA) upon a set of covariance matrices. A metrics is then built to
      quantify the similitude distance. This is based on the degree of variance
      extraction achieved for each variable along the GPCA deflation processes by the
      common factors. This permits a cluster analysis, which recognizes several compact
      sub-sets containing only the most closely related responsive groups. The GPCA is
      then run again but is restricted to the groups in each sub-set. Finally, after
      the data have been exhaustively deflated by the common sub-set factors, the
      resulting residual matrices are used to determine the specific response factors
      by classical principal component analysis (PCA). The proposed method was
      validated by comparing its predictions with those obtained when the dynamics of
      the perturbation was determined. In addition, it showed to have a better
      performance than the obtained with other multivariate alternatives (e.g.,
      orthogonal contrasts based on direct GPCA, Tucker-3 model, PARAFAC, etc.).

PMID- 19603429
TI  - RUNX3-mediated repression of RUNX1 in B cells.
AB  - Are there three different RUNX genes in the human genome just to allow
      differential expression in different cell types or are the RUNX proteins
      functionally different? Much previous evidence has suggested that the RUNX
      proteins were functionally redundant but, in human B cells, RUNX1 and RUNX3 have
      clearly been shown to have different functions at a key developmental stage.
      RUNX1 is expressed in mature resting B cells but proliferating B cell lines
      express RUNX3. Repression of RUNX1 by RUNX3 is required to allow the cell
      proliferation and this provides an experimental system to investigate the
      mechanism of the different activities of RUNX1 and RUNX3 in these cells.

PMID- 19603430
TI  - Validation of self-reported occupational exposures in meatpacking workers.
AB  - OBJECTIVE: The ability of workers to accurately recall exposures that occur on
      the day of their injury is considered a potential limitation of case-crossover
      studies. This study assessed validity of occupational exposures reported by
      uninjured workers at a Midwestern meatpacking plant. METHODS: One hundred thirty
      six workers were observed for 60 min while working and then interviewed within 8
      days (median 3 days) about exposures during the observation period. The level of
      agreement between self-reports and direct observations was assessed using kappas
      and intraclass correlation coefficients. RESULTS: Excellent agreement was found
      between observed and reported work location (kappa = 0.97, 95% CI: 0.92-1.0),
      task (kappa = 0.83, 95% CI: 0.76-0.91) and tools used (kappa = 0.88, 95% CI: 0.81
      0.95). Personal protective equipment varied by work type and location, and
      agreement between observed and reported usage varied from excellent to poor for
      various items. Excellent agreement was found for tool sharpening (kappa = 0.89,
      95% CI: 0.82-0.97); good agreement for occurrence of break during the observation
      period (kappa = 0.60, 95% CI: 0.45-0.74); and poor agreement for equipment
      malfunction, line stoppages, being tired, unusual task, unusual work method,
      being distracted, rushing, slipping, or falling. CONCLUSIONS: Agreement between
      observed and reported occupational exposures varied widely. Self-reported
      exposures are utilized in many occupational studies, and future exposure validity
      assessment studies should continue to improve retrospective study methods. Valid
      exposures will allow researchers to better understand injury etiology and
      ultimately prevent injuries from occurring.

PMID- 19603431
TI  - Ion-pair binding: is binding both binding better?
AB  - It is often tempting to explain chemical phenomena on the basis of intuitive
      principles, but this practice can frequently lead to biased analysis of data and
      incorrect conclusions. One such intuitive principle is brought into play in the
      binding of salts by synthetic receptors. Following the heuristic concept that
      "binding both is binding better", it is widely believed that ditopic receptors
      capable of binding both ionic partners of a salt are more effective than
      monotopic receptors because of a cooperative effect. Using a newly designed
      ditopic receptor and a generalized binding descriptor, we show here that, when
      the problem is correctly formulated and the appropriate algorithm is derived, the
      cooperativity principle is neither general nor predictable, and that competition
      between ion binding and ion pairing may even lead to inhibition rather than
      enhancement of the binding of an ion to a ditopic receptor.

PMID- 19603432
TI  - Photoinduced formation and characterization of electron-hole pairs in
      azaxanthylium-derivatized short single-walled carbon nanotubes.
AB  - 2-Azaxanthone, a nitrogenated derivative of the well-studied organic chromophore
      xanthone, has been covalently bound through 2-(ethylthio)ethylamido linkers to
      the carboxylic acid groups of short, soluble single-walled carbon nanotubes
      (CNTs) of 450 nm average length, and the resulting azaxanthylium-functionalized
      CNTs (AZX-CNT, 8.5 wt % AZX content) characterized by solution (1)H NMR, Raman
      and IR spectroscopy and thermogravimetric analysis. Comparison of the quenching
      of the triplet excited state of AZX (steady-state and time-resolved) and of the
      transient optical spectra of CNTs and AZX-CNT shows that the covalent linkage
      boosts the interaction between the azaxanthylium moiety and the short CNT units.
      The triplet excited state of the azaxanthylium derivative is quenched by CNT with
      and without covalent bonding, but when it is covalently bonded, the singular
      transient spectrum is compatible with the photogeneration of electron holes
      through electron transfer from CNT to excited azaxanthylium units.

PMID- 19603433
TI  - Systematic investigation of molecular arrangements and solid-state fluorescence
      properties on salts of anthracene-2,6-disulfonic acid with aliphatic primary
      amines.
AB  - Organic salts of anthracene-2,6-disulfonic acid (ADS) with a wide variety of
      primary amines have been fabricated, and their arrangements of anthracene
      molecules and solid-state fluorescence properties investigated. Single-crystal X
      ray studies reveal that the salts show seven types of crystal forms and
      corresponding molecular arrangements of anthracene moieties depending on the
      amine, while anthracene shows only one form and arrangement in the solid state.
      Depending on the molecular arrangements, the ADS salts exhibit various solid
      state fluorescence properties: spectral shift (30 nm) and suppression and
      enhancement of the fluorescence intensity. Especially the ADS salt with n
      heptylamine (nHepA), which shows discrete anthracene moieties in the crystal,
      exhibits the highest quantum yield (Phi(F)=46.1+/-0.2%) in the series of ADS
      salts, which exceeds that of anthracene crystal (Phi(F)=42.9+/-0.2%). From these
      systematic investigations on the arrangements and the solid-state properties, the
      following factors are essential for high fluorescence quantum yield in the solid
      state: prevention of contact between pi planes of anthracene moieties and
      immobilization of anthracene rings. In addition, such organic salts have
      potential as a system for modulating the molecular arrangements of fluorophores
      and the concomitant solid-state properties. Thus, systematic investigation of
      this system constructs a library of arrangements and properties, and the library
      leads to remarkable strategies for the development of organic solid materials.

PMID- 19603434
TI  - Molecular complexes of simple anions with electron-deficient arenes:
      spectroscopic evidence for two types of structural motifs for anion-arene
      interactions.
AB  - Anion-pi interactions between a pi-acidic aromatic system and an anion are
      gaining increasing recognition in chemistry and biology. Herein, the binding
      features of an electron-deficient aromatic system (1,3,5-trinitrobenzene (TNB))
      and selected anions (OH-, Br-, and I-) are examined in the gas phase by using the
      combined information derived from collision-induced dissociation experiments at
      variable energy, infrared multiple-photon dissociation spectroscopy, and quantum
      chemical calculations. We provide spectroscopic evidence for two different
      structural motifs of anion-arene complexes depending on the nature of the anion.
      The TNB-OR- complexes (R=H, or alkyl groups which were studied earlier) adopt an
      anionic sigma-complex structure whereby RO- attacks the aromatic ring with
      covalent bond formation, and develops a tetrahedral ring carbon bound to H and
      OR. The halide complexes rather conform to a structure in which the TNB moiety is
      hardly altered, and the halogen is placed on an unsubstituted carbon atom over
      the periphery of the ring at a C-X distance that is appreciably longer than a
      typical covalent bond length. The ensuing structural motif, previously
      characterized in the solid state and named weak sigma interaction, is now
      confirmed by an IR spectroscopic assay in the gas phase, in which the sampled
      species are unperturbed by crystal packing or solvation effects.

PMID- 19603435
TI  - Electrochemical characterisation of 6-iodomaltose, 6'-iodomaltose and 6
      iodomaltotriose on a silver cathode and their one-pot electrochemical
      dimerisation to new mixed O/C maltotetraose and maltohexaose mimics.
AB  - The electrochemical reduction on silver of peracetylated 6-iodo-6-deoxy-beta
      maltose (2), 6-iodo-6-deoxy-beta-maltotriose (3) and 6'-iodo-6'-deoxy-beta
      maltose (4) has been investigated by cyclic voltammetry and performed on a
      preparative scale, according to the stoichiometry, -CH(2)I(2-4) + e(-) --> 
      CH(2)(*) + I(-). In agreement with the preparative electrolysis results, cyclic
      voltammetry showed different profiles for the reducing terminal-iodinated 2 and 3
      and for the non-reducing terminal-iodinated 4. Compounds 2 and 3 partly dimerised
      to maltotetraoses mimics 7 (6,6-dimer) and 8 (5',5'-dimer) in 38% overall yield
      and to maltohexaose mimics 12 (6,6-dimer) and 13 (5',5'-dimer) in 30% overall
      yield, respectively. Compounds 7 and 12 came from the dimerisation of -CH(2)(*),
      primary radicals at C-6, which could also abstract H-5', becoming CH(3) and
      generating the C-5' quaternary radicals that dimerised in 8 and 13, respectively.
      These products were accompanied by the maltose derivatives 9, 10 and 11 a/b in
      42% overall yield and by the maltotriose derivatives 14, 15 and 16 in 48% overall
      yield, respectively. Compounds 9, 14 and 10, 15 came from -CH(2)(*)
      disproportionation to CH(3) and CH(2)=C, respectively (exocyclic double bond C
      6/C-5). Compounds 11 a/b and 16 came from C-5' radical reduction, followed by
      acetate anion elimination (double bonds C-6'/C-5' and C-5'/C-4'). In turn, 4
      afforded only the 6',6'-dimer maltotetraose mimic 17 in 60% yield, accompanied by
      the reduced maltose 18 in 20% yield, in which the starting CH(2)I became CH(3).
      Compounds 7, 8, 12, 13 and 17 belong to a class of mixed O/C malto-mimic
      oligosaccharides wherein an unnatural C-C bond between two saccharide units
      increases metabolic stability compared to their O-analogues and modulates the
      sugar chain conformational flexibility, a fundamental parameter in determining
      protein-carbohydrate binding. Direct and spin-trapping EPR studies substantiated
      the radical-based nature of the dimerisation processes and allowed the
      identification of some of the paramagnetic species involved.

PMID- 19603436
TI  - Bisphosphine-functionalized cyclic decapeptides based on the natural product
      Gramicidin S: a potential scaffold for transition-metal coordination.
AB  - The natural product Gramicidin S is a promising scaffold for novel oligopeptide
      based bisphosphine ligands, combining the advantageous rigid chiral backbone with
      the close proximity of phosphine substituents. The required unnatural, phosphine
      containing, amino acid building blocks were synthesized by means of a novel
      protocol that involves the enantioselective alkylation of a chiral nickel Schiff
      base template. Three Ni complexes were prepared with different alkyl chains
      between the phosphine group and the alpha-carbon atom of the incorporated
      glycine; the absolute stereochemistry of two of them was determined by single
      crystal X-ray structure analysis. By detaching the template, enantiopure L
      phosphine amino acids resulted enabling the solid-phase, stepwise construction of
      a linear sequence of the phosphine-modified oligopeptides. On cyclization three
      bisphosphine-substituted Gramicidin S analogues resulted, differing only in the
      size and shape of the linkage between the phosphine groups and the oligopeptides
      backbone. Their crystal structures suggest these species to have potential as
      chelating ligands.

PMID- 19603439
TI  - Main-group-metal clusters stabilized by N-heterocyclic carbenes.

PMID- 19603438
TI  - A gold-catalyzed cascade reaction involving an unusual intramolecular redox
      process.

PMID- 19603437
TI  - Single molecule force spectroscopy on G-quadruplex DNA.

PMID- 19603440
TI  - Dehydrogenative dimerization of di-tert-butyltin dihydride photochemically and
      thermally catalyzed by iron and molybdenum complexes.

PMID- 19603441
TI  - Heck reactions with palladium nanoparticles in ionic liquids: coupling of aryl
      chlorides with deactivated olefins.

PMID- 19603442
TI  - Charge transfer assisted by collective hydrogen-bonding dynamics.

PMID- 19603443
TI  - Real-time monitoring of organic reactions with two-dimensional ultrafast TOCSY
      NMR spectroscopy.

PMID- 19603445
TI  - Solvent-free protein liquids and liquid crystals.

PMID- 19603446
TI  - Identification of flavopiridol analogues that selectively inhibit positive
      transcription elongation factor (P-TEFb) and block HIV-1 replication.
AB  - The positive transcription elongation factor (P-TEFb; CDK9/cyclin T1) regulates
      RNA polymerase II-dependent transcription of cellular and integrated viral genes.
      It is an essential cofactor for HIV-1 Tat transactivation, and selective
      inhibition of P-TEFb blocks HIV-1 replication without affecting cellular
      transcription; this indicates that P-TEFb could be a potential target for
      developing anti-HIV-1 therapeutics. Flavopiridol, a small molecule CDK inhibitor,
      blocks HIV-1 Tat transactivation and viral replication by inhibiting P-TEFb
      kinase activity, but it is highly cytotoxic. In the search for selective and less
      cytotoxic P-TEFb inhibitors, we prepared a series of flavopiridol analogues and
      evaluated their kinase inhibitory activity against P-TEFb and CDK2/cyclin A, and
      tested their cellular antiviral potency and cytotoxicity. We identified several
      analogues that selectively inhibit P-TEFb kinase activity in vitro and show
      antiviral potency comparable to that of flavopiridol, but with significantly
      reduced cytotoxicity. These compounds are valuable molecular probes for
      understanding P-TEFb-regulated cellular and HIV-1 gene transcription and provide
      potential anti-HIV-1 therapeutics.

PMID- 19603448
TI  - Effects of fullerenes on phospholipid membranes: a langmuir monolayer study.
AB  - We investigate two-component Langmuir monolayers of
      dipalmitoylphosphatidylcholine (DPPC)/C(60) by recording surface pressure/area
      (pi/A) and surface potential/area (DeltaV/A) isotherms and by direct Brewster
      angle microscopy (BAM) imaging. Atomic force microscopy (AFM) is employed to
      study morphologies of the mixed monolayers transferred to a solid substrate by
      the Langmuir-Blodgett technique. C(60) is shown to have little influence on
      isotherms of the DPPC/C(60) monolayers even at a molar fraction as high as
      X(C60)=0.3. The elastic modulus (Cs(-1) versus pi curves of the DPPC/C(60)
      monolayers almost overlay each other, as well as that of pure DPPC, that is, the
      elasticities of pure DPPC monolayers and DPPC/C(60) monolayers are remarkably
      similar. AFM studies reveal that fullerene flocs form at low surface pressures
      (pi<or=15 mN m(-1)), are gradually disaggregated and dispersed in the DPPC
      monolayer with increasing surface pressure up to 35 mN m(-1), and are then
      progressively squeezed out to form protruded islands as the surface pressure
      increases up to 65 mN m(-1). Our work provides experimental support to the
      computational result that C(60) can dissolve in lipid bilayers without
      significantly compromising their mechanical properties, a finding which has
      important implications for the toxicity and development of drug vehicles from
      fullerene materials.

PMID- 19603447
TI  - Nondestructively creating nanojunctions by combined-dynamic-mode dip-pen
      nanolithography.

PMID- 19603450
TI  - Low-power solid-state NMR experiments for resonance assignment under fast magic
      angle spinning.

PMID- 19603449
TI  - Bimetallic nickel-iron impurities within single-walled carbon nanotubes exhibit
      redox activity towards the oxidation of amino acids.

PMID- 19603451
TI  - Rhenium- and manganese-catalyzed insertion of alkynes into a carbon-carbon single
      bond of cyclic and acyclic 1,3-dicarbonyl compounds.
AB  - Treatment of alkynes with cyclic and acyclic 1,3-dicarbonyl compounds in the
      presence of a catalytic amount of a rhenium or manganese complex gives ring
      expanded and carbon-chain extension products, respectively. In these reactions,
      alkynes insert into a non-strained carbon-carbon single bond of 1,3-dicarbonyl
      compounds. The ring-expansion reaction is also promoted by the addition of 4-A
      molecular sieves instead of a catalytic amount of an isocyanide.

PMID- 19603453
TI  - De novo synthesis and assembly of multiplex riboswitches in vitro.
AB  - Pools of short synthetic oligonucleotides (oligos) are required in the multiplex
      and parallel DNA construction. Microarray technology provides a fast and
      economical mean for massive parallel synthesis of oligos. The method of oligo
      synthesis with the programmable microfluidic PicoArray could simultaneously
      synthesize the designed oligos for multiple riboswitch genes. The synthetic
      oligos were recovered and purified as a pool of oligo mixture (OligoMix). Three
      temperature steps were employed to denature, anneal and extend the designed
      OligoMix until, after multiple rounds of thermocycling, the riboswitches with the
      desired length are obtained. The OligoMix was amplified using this PCR-based
      technique and the flanking adapter segments were cleaved for following assembly.
      Based on these oligos derived from 197 riboswitch sequences, the method of
      simultaneous assembling multiplex riboswitches (SAMRs) showed high fidelity by
      sequence identification. The resultant error rate was determined to be 2.78 per
      thousand. With the templates from SAMRs, in vitro transcription was applied to
      produce milligram amounts of biologically active riboswitches. With the
      verification of biological activity based on the high specificity of recognizing
      small-molecule metabolites as well as the DNA sequence redivivus by RT-PCR, the
      assembled riboswitches can be used for further gene operation and biological
      application.

PMID- 19603452
TI  - Fractionation of transgenic corn seed by dry and wet milling to recover
      recombinant collagen-related proteins.
AB  - Corn continues to be considered an attractive transgenic host for producing
      recombinant therapeutic and industrial proteins because of its potential for
      producing recombinant proteins at large volume and low cost as coproducts of corn
      seed-based biorefining. Efforts to reduce production costs have been primarily
      devoted to increasing accumulation level, optimizing protein extraction
      conditions, and simplifying the purification. In the present work, we evaluated
      two grain fractionation methods, dry milling and wet milling, to enrich two
      recombinant collagen-related proteins; thereby, reducing the amount and type of
      corn-derived impurities in subsequent protein extraction and purification steps.
      The two proteins were a full-length human recombinant collagen type I alpha
      1(rCIalpha1) chain with telopeptides and peptide foldon to effect triple helix
      formation and a 44-kDa rCIalpha1 fragment. For each, approximately 60% of the
      rCIalpha1s in the seed was recovered in the dry-milled germ-rich fractions making
      up ca. 25% of the total kernel mass. For wet milling, approximately 60% of each
      was recovered in three fractions accounting for 20-25% of the total kernel mass.
      The rCIalpha1s in the dry-milled germ-rich fractions were enriched three to six
      times compared with the whole corn kernel, whereas the rCIalpha1s were enriched 4
      10 times in selected wet-milled fractions. The recovered starch from wet milling
      was almost free of rCIalpha1. Therefore, it was possible to generate rCIalpha1
      enriched fractions by both dry and wet milling along with rCIalpha1-free starch
      using wet milling. Because of its simplicity, the dry milling procedure could be
      accomplished on-farm thus minimizing the risk of inadvertent release of viable
      transgenic seeds.

PMID- 19603454
TI  - Lightning-induced ECG changes and hydrostatic pulmonary edema.

PMID- 19603455
TI  - Multielement (H, C, N, O, S) stable isotope characteristics of lamb meat from
      different Italian regions.
AB  - The study focuses on the (2)H/H, (13)C/(12)C, (15)N/(14)N, (18)O/(16)O and
      (34)S/(32)S values of defatted dry matter (DFDM) and on the (2)H/H, (13)C/(12)C
      and (18)O/(16)O values of the fat fraction of meat samples from various lamb
      types reared in seven Italian regions, following different feeding regimes
      (forage, concentrate, milk). The (13)C/(12)C (r = 0.922), (2)H/H (r = 0.577) and
      (18)O/(16)O (r = 0.449) values of fat and DFDM are significantly correlated, the
      fat values being significantly lower for C and H and higher for O than for DFDM
      values and the differences between the two fractions not being constant for
      different lamb types. The feeding regime significantly affected the (13)C/(12)C,
      (15)N/(14)N, (18)O/(16)O and (2)H/H of fat. The DFDM (2)H/H, and (18)O/(16)O
      values, excluding an outlier, are significantly correlated with the corresponding
      values in meteoric waters, thus allowing us to trace the variability of
      geoclimatic factors. (15)N/(14)N is influenced by pedoclimatic conditions,
      whereas (34)S/(32)S is influenced by the sea spray effect and the surface geology
      of the provenance area. By applying stepwise linear discriminant analysis only
      the (2)H/H of fat was found not to be significant and 97.7% of the samples were
      correctly assigned to the lamb type and more than 90% cross-validated. With the
      feeding regime, 97.7% of the samples were both correctly assigned and cross
      validated using a predictive model including (13)C/(12)C, (15)N/(14)N,
      (18)O/(16)O, (34)S/(32)S of DFDM and (18)O/(16)O of fat.

PMID- 19603456
TI  - Study of isotopic variations in black powder: reflections on the use of stable
      isotopes in forensic science for source inference.
AB  - Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the
      forensic community. This high-precision technology has already been applied to a
      broad range of forensic fields such as illicit drugs, explosives and flammable
      liquids, where current, routinely used techniques have limited powers of
      discrimination. The conclusions drawn from the majority of these IRMS studies
      appear to be very promising. Used in a comparative process, as in food or drug
      authentication, the measurement of stable isotope ratios is a new and remarkable
      analytical tool for the discrimination or the identification of a substance with
      a definite source or origin. However, the research consists mostly of preliminary
      studies. The significance of this 'new' piece of information needs to be
      evaluated in light of a forensic framework to assess the actual potential and
      validity of IRMS, considering the characteristics of each field. Through the
      isotopic study of black powder, this paper aims at illustrating the potential of
      the method and the limitations of current knowledge in stable isotopes when
      facing forensic problems.

PMID- 19603457
TI  - Study of mineral water resources from the Eastern Carpathians using stable
      isotopes.
AB  - The Eastern Carpathians contain many mineral water springs that feed famous
      Romanian health resorts such as Borsec, Biborteni and Vatra Dornei. These waters
      have been used for their different therapeutic effects. In this work, mineral and
      spring waters from these Romanian regions were investigated by means of chemical
      and isotopic (deltaD and delta(18)O) analyses in order to understand the recharge
      mechanisms and also to determine their origins. Most of the investigated springs
      are of meteoric origin, having the average deuterium content of the local
      meteoric water. The higher (18)O content with respect to the Meteoric Water Line
      (MWL) indicated an exchange reaction with crystalline igneous rocks at depth and
      with other rocks that the water encounters on its journey back to the surface.

PMID- 19603458
TI  - Isotopic characteristics of the Garonne River and its tributaries.
AB  - The Garonne is the largest river in the south-west of France, and its drainage
      basin stretches between the Pyrenees and the Massif Central mountains. Until now,
      no water stable isotope study has been performed on the whole Garonne river basin
      which is composed of different geological substrata, and where the water
      resources are limited during the dry summer period. This study focuses on the
      Garonne river and its tributaries from the Pyrenees foothill upstream to its
      confluence with the Lot River downstream. The aim of the study is to determine
      the origins of the surface waters using their chemical and stable isotopic
      compositions ((18)O, D and (13)C), to better understand their circulation within
      the drainage basin and to assess the anthropogenic influences. The Garonne
      displays a specific (18)O seasonal effect, and keeps its Pyrenean characteristics
      until its confluence with the Tarn River. The difference in the dissolved
      inorganic carbon (DIC) comes mainly from the change in lithology between the
      Pyrenees and the Massif Central mountains. Agriculture activity is only detected
      in the small tributaries.

PMID- 19603459
TI  - Demonstration of high-precision continuous measurements of water vapor
      isotopologues in laboratory and remote field deployments using wavelength-scanned
      cavity ring-down spectroscopy (WS-CRDS) technology.
AB  - This study demonstrates the application of Wavelength-Scanned Cavity Ring-Down
      Spectroscopy (WS-CRDS) technology which is used to measure the stable isotopic
      composition of water. This isotopic water analyzer incorporates an evaporator
      system that allows liquid water as well as water vapor to be measured with high
      precision. The analyzer can measure H2(18)O, H2(16)O and HD(16)O content of the
      water sample simultaneously. The results of a laboratory test and two field
      trials with this analyzer are described. The results of these trials show that
      the isotopic water analyzer gives precise, accurate measurements with little or
      no instrument drift for the two most common isotopologues of water. In the
      laboratory the analyzer has a precision of 0.5 per mil for deltaD and 0.1 per mil
      for delta(18)O which is similar to the precision obtained by laboratory-based
      isotope ratio mass spectrometers. In the field, when measuring vapor samples, the
      analyzer has a precision of 1.0 per mil for deltaD and 0.2 per mil for
      delta(18)O. These results demonstrate that the isotopic water analyzer is a
      powerful tool that is appropriate for use in a wide range of applications and
      environments.

PMID- 19603460
TI  - Is there any 12C/13C fractionation during starch remobilisation and sucrose
      export in potato tubers?
AB  - The delta(13)C (carbon isotope composition) variations in respired CO(2), total
      organic matter, proteins, sucrose and starch have been measured during tuber
      sprouting of potato (Solanum tuberosum) in darkness. Measurements were carried
      out both on tubers and on their growing sprouts for 23 days after the start of
      sprout development. Sucrose was slightly (13)C-depleted compared with starch in
      tubers, suggesting that starch breakdown was associated with a small isotope
      fractionation. In sprouts, all biochemical fractions including sucrose were (13)C
      enriched compared with source tuber-sucrose, suggesting that sucrose
      translocation from tuber to sprouts fractionated against (12)C. However, both
      apparent fractionations were explained by the consumption of (13)C-depleted
      carbon for respiration or growth that enriched in the (13)C sucrose molecules
      left behind. In addition, whole tuber sucrose is constantly composed of recent
      sucrose from starch breakdown and old sucrose associated with an inherited,
      slightly (13)C-depleted pool. We therefore conclude that any fractionation at
      either the starch breakdown or the sucrose translocation level is unlikely under
      our conditions.

PMID- 19603461
TI  - Development and evaluation of a high-performance liquid chromatography/isotope
      ratio mass spectrometry methodology for delta13C analyses of amino sugars in
      soil.
AB  - Amino sugars have been used as biomarkers to assess the relative contribution of
      dead microbial biomass of different functional groups of microorganisms to soil
      carbon pools. However, little is known about the dynamics of these compounds in
      soil. The isotopic composition of individual amino sugars can be used as a tool
      to determine the turnover of these compounds. Methods to determine the delta(13)C
      of amino sugars using gas chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS) have been proposed in literature. However, due to
      derivatization, the uncertainty on the obtained delta(13)C is too high to be used
      for natural abundance studies. Therefore, a new high-performance liquid
      chromatography/isotope ratio mass spectrometry (HPLC/IRMS) methodology, with
      increased accuracy and precision, has been developed. The repeatability on the
      obtained delta(13)C values when pure amino sugars were analyzed were not
      significantly concentration-dependent as long as the injected amount was higher
      than 1.5 nmol. The delta(13)C value of the same amino sugar spiked to a soil
      deviated by only 0.3 per thousand from the theoretical value.

PMID- 19603462
TI  - Carbon stable isotope ratio of phloem sugars in mature pine trees throughout the
      growing season: comparison of two extraction methods.
AB  - The study presents a comparison of two phloem sugar extraction methods. The
      amount of phloem sugar extracted and the carbon isotope composition (delta(13)C)
      of the total extracts and of the main phloem compounds separated by high
      performance liquid chromatography (sucrose, glucose, fructose and pinitol) are
      compared. These two phloem sap extraction methods are exudation in distilled
      water and a new method using centrifugation, which avoids the addition of any
      solvent. We applied both extraction methods on phloem discs sampled from 38-year
      old Pinus pinaster trees in south-western France throughout the period from June
      2007 to December 2008 on different time-scales: hourly, daily and monthly. We
      found that the centrifugation method systematically extracted ca. 50% less
      compounds from the phloem discs than the exudation method. In addition, the two
      extraction methods provided similar delta(13)C values of the total extracts, but
      the values obtained by the exudation method were 0.6 per thousand more negative
      than those calculated from the mass balance using the individual constituents.
      Over the growing season, both extraction methods exhibited lower total sugar
      content and more (13)C-enriched phloem sap in summer compared with winter values.
      These findings suggest that both extraction methods can be applied to study the
      carbon isotope composition of phloem sap, and the centrifugation method has the
      advantage that no solvent has to be added. The exudation method, however, is more
      appropriate for the quantification of the amounts of phloem sugars.

PMID- 19603464
TI  - The influence of preservation method and time on the delta13C value of dissolved
      inorganic carbon in water samples.
AB  - The precise delta(13)C value of dissolved inorganic carbon (DIC) is important for
      various types of ecological studies. Without a preservation agent, microbial
      degradation of organic compounds continues in water samples and the delta(13)C
      value of DIC will become more depleted with time. HgCl(2) or acidification is
      often used to prevent microbial activity in water samples collected for carbon
      isotope ratio analyses of DIC. Mercury compounds are toxic and result in waste
      disposal problems. Other inhibiting agents or preservation methods are therefore
      needed. Two possible solutions are to use copper sulphate (CuSO(4)) as a
      preservative agent or to acidify water samples with phosphoric acid (H(3)PO(4))
      within 12 mL measurement Exetainers (septum-capped vials). We prepared a set of
      lake water samples in three types of vials: glass vials with silicone/PTFE septa,
      high-density polyethylene vials (HD-PE, scintillation vials) and Exetainers (12
      mL) with butyl rubber septa. Samples in glass and PE vials were preserved with
      and without CuSO(4), whereas lake water was injected into the Exetainer and
      acidified with H(3)PO(4). Isotope ratios were measured in two laboratories over 6
      months. The delta(13)C values of DIC systematically increased with storage time
      for samples preserved in glass and PE vials with and without CuSO(4). A strong
      correlation between a decrease of CO(2) concentration and an increase in DIC
      delta(13)C values was found. The delta(13)C values and DIC concentrations were
      stable for 6 months in acidified samples stored in Exetainers with butyl rubber
      septa. Therefore, we conclude that the best method for up to 6 months of storage
      is to inject samples in the field into butyl rubber septum capped Exetainers
      containing H(3)PO(4), thereby avoiding the use of preservatives.

PMID- 19603463
TI  - Preparation of starch and soluble sugars of plant material for the analysis of
      carbon isotope composition: a comparison of methods.
AB  - Starch and soluble sugars are the major photosynthetic products, and their carbon
      isotope signatures reflect external versus internal limitations of CO(2)
      fixation. There has been recent renewed interest in the isotope composition of
      carbohydrates, mainly for use in CO(2) flux partitioning studies at the ecosystem
      level. The major obstacle to the use of carbohydrates in such studies has been
      the lack of an acknowledged method to isolate starch and soluble sugars for
      isotopic measurements. We here report on the comparison and evaluation of
      existing methods (acid and enzymatic hydrolysis for starch; ion-exchange
      purification and compound-specific analysis for sugars). The selectivity and
      reproducibility of the methods were tested using three approaches: (i) an
      artificial leaf composed of a mixture of isotopically defined compounds, (ii) a
      C(4) leaf spiked with C(3) starch, and (iii) two natural plant samples (root,
      leaf). Starch preparation methods based on enzymatic or acid hydrolysis did not
      yield similar results and exhibited contaminations by non-starch compounds. The
      specificity of the acidic hydrolysis method was especially low, and we therefore
      suggest terming these preparations as HCl-hydrolysable carbon, rather than
      starch. Despite being more specific, enzyme-based methods to isolate starch also
      need to be further optimized to increase specificity. The analysis of sugars by
      ion-exchange methods (bulk preparations) was fast but produced more variable
      isotope compositions than compound-specific methods. Compound-specific approaches
      did not in all cases correctly reproduce the target values, mainly due to
      unsatisfactory separation of sugars and background contamination. Our study
      demonstrates that, despite their wide application, methods for the preparation of
      starch and soluble sugars for the analysis of carbon isotope composition are not
      (yet) reliable enough to be routinely applied and further research is urgently
      needed to resolve the identified problems.

PMID- 19603465
TI  - Kinetic 12C/13C isotope fractionation by invertase: evidence for a small in vitro
      isotope effect and comparison of two techniques for the isotopic analysis of
      carbohydrates.
AB  - The natural (13)C/(12)C isotope composition (delta(13)C) of plants and organic
      compounds within plant organs is a powerful tool to understand carbon allocation
      patterns and the regulation of photosynthetic or respiratory metabolism. However,
      many enzymatic fractionations are currently unknown, thus impeding our
      understanding of carbon trafficking pathways within plant cells. One of them is
      the (12)C/(13)C isotope effect associated with invertases (EC 3.2.1.26) that are
      cornerstone enzymes for Suc metabolism and translocation in plants. Another
      conundrum of isotopic plant biology is the need to measure accurately the
      specific delta(13)C of individual carbohydrates. Here, we examined two
      complementary methods for measuring the delta(13)C value of sucrose, glucose and
      fructose, that is, off-line high-performance liquid chromatography (HPLC)
      purification followed by elemental analysis and isotope ratio mass spectrometry
      (EA-IRMS) analysis, and gas chromatography-combustion (GC-C)-IRMS. We also used
      these methods to determine the in vitro (12)C/(13)C isotope effect associated
      with the yeast invertase. Our results show that, although providing more variable
      values than HPLC approximately EA-IRMS, and being sensitive to derivatization
      conditions, the GC-C-IRMS method gives reliable results. When applied to the
      invertase reaction, both methods indicate that the (12)C/(13)C isotope effect is
      rather small and it is not affected by the use of heavy water (D(2)O).

PMID- 19603466
TI  - Contribution of nitrification and denitrification to nitrous oxide emissions from
      soils after application of biogas waste and other fertilizers.
AB  - The attribution of nitrous oxide (N(2)O) emission to organic and inorganic N
      fertilizers requires understanding of how these inputs affect the two biological
      processes, i.e. denitrification and nitrification. Contradictory findings have
      been reported when the effects of organic and inorganic fertilizers on nitrous
      oxide emission were compared. Here we aimed to contribute to the understanding of
      such variation using (15)N-labelling techniques. We determined the processes
      producing N(2)O, and tested the effects of soil moisture, N rates, and the
      availability of organic matter. In a pot experiment, we compared soil treated
      with biogas waste (BGW) and mineral ammonium sulphate (Min-N) applied at four
      rates under two soil moisture regimes. We also tested biogas waste, conventional
      cattle slurry and mineral N fertilizer in a grassland field experiment. During
      the first 37 days after application we observed N(2)O emissions of 5.6 kg N(2)O-N
      ha(-1) from soils supplied with biogas waste at a rate of 360 kg N ha(-1). Fluxes
      were ca. 5-fold higher at 85% than at 65% water holding capacity (WHC). The
      effects of fertilizer types and N rates on N(2)O emission were significant only
      when the soil moisture was high. Organic fertilizer treated soils showed much
      higher N(2)O emissions than those receiving mineral fertilizer in both, pot and
      field experiment. Over all the treatments the percentage of the applied N emitted
      as N(2)O was 2.56% in BGW but only 0.68% in Min-N. In the pot experiment isotope
      labelling indicated that 65-95% of the N(2)O was derived from denitrification for
      all fertilizer types. However, the ratio of denitrification/nitrification derived
      N(2)O was lower at 65% than at 85% WHC. We speculate that the application of
      organic matter in conjunction with ammonium nitrogen first leads to a decrease in
      denitrification-derived N(2)O emission compared with soil receiving mineral
      fertilizer. However, at later stages when denitrification becomes C-limited,
      higher N(2)O emissions are induced when the soil moisture is high.

PMID- 19603467
TI  - Blood volume and red cell mass in children with moderate and severe malaria
      measured by chromium-53 dilution and gas chromatography/mass spectrometric
      analysis.
AB  - Understanding blood volume changes in children with malaria is important for
      managing fluid status. Traditionally, blood/red cell volume measurements have
      used radioactive chromium isotopes. We applied an alternative approach, using non
      radioactive chromium-53 labelling and mass spectrometry to investigate red cell
      volume (RCV) in Gabonese children with malaria. Nineteen children with malaria
      participated (10 severe, 9 moderately severe; ages 15 months to 7 years). Blood
      labelled with (53)Cr-chromate ex vivo was re-injected, then sampled 30 min later.
      Pre- and post-injection (53)Cr content were measured by gas
      chromatography/electron ionisation mass spectrometry of the chromium
      trifluoroacetylacetone (TFA) chelate, calibrated against (50)Cr standards. Blood
      and red cell volumes were calculated from isotopic dilution in 15 of 19 children
      (in four, insufficient signal mitigated analysis). In this small pilot study,
      there were no significant differences between moderate and severe cases.
      Including all subjects, the mean RCV was reduced compared with predicted values
      (184 vs. 269 mL; p = 0.016) but blood volume, 71 +/- 33 mL/kg (normalised for
      weight), was close to predicted, approximately 77 mL/kg, commensurate with
      reduced haematocrit. Blood lactate concentration correlated negatively with
      RCV/weight (r = -0.56, p = 0.028), consistent with anaemia. In one case,
      sequential samples over 42 days gave an estimated rate of (53)Cr disappearance of
      1.4%/day (equivalent half-life: 70 days). (53)Cr-labelling of red cells may be
      used to estimate blood and red cell volumes and can be used as an investigative
      tool in situations such as childhood diseases and resource-constrained settings.
      Although the red cell mass is depleted in malaria, the blood volume appears
      relatively well preserved.

PMID- 19603468
TI  - On the application of a ZrO2-based solid electrolyte in isotope ratio mass
      spectrometry.
AB  - The application of a high-temperature electrochemical reactor based on stabilized
      zirconium dioxide (0.9 ZrO(2)0.1 Y(2)O(3)) for organic gas sampling in continuous
      flow isotope-ratio mass spectrometry (CF-IRMS) has been found to be efficient.
      This solid electrolyte reactor (SER) can also be used as a chromatographic
      detector for the quantitative measurements of organic gases. A three-electrode
      SER system was studied. Complete stoichiometric oxidation of organic gases has
      been achieved at 900-950 degrees C due to the large catalytic surface area of the
      porous platinum coating. At this temperature, the oxygen ions formed from the
      oxygen of ambient air on the outer surface of the reactor migrate through the
      solid electrolyte under the action of the applied electric field and allow
      combustion of gases being analyzed to be effected. It should be noted that oxygen
      gas was not introduced into the gas-carrier flow. Similar results for the
      measurements of carbon isotope ratios were obtained at the oxidation of
      hydrocarbon gases in both the standard and the solid electrolyte reactors.

PMID- 19603469
TI  - Consistent patterns in leaf lamina and leaf vein carbon isotope composition
      across ten herbs and tree species.
AB  - Wide-spread post-photosynthetic fractionation processes deplete metabolites and
      plant compartments in (13)C relative to assimilates to varying degrees.
      Fragmentation fractionation and exchange of metabolites with distinct isotopic
      signatures across organ boundaries further modify the patterns of plant isotopic
      composition. Heterotrophic organs tend to become isotopically heavier than the
      putative source material as a result of respiratory metabolism. In addition
      fractionation may occur during metabolite transport across organ and tissue
      boundaries. Leaf laminae, veins and petioles are leaf compartments that are
      arranged along a gradient of increasing weight of heterotrophic processes and
      along a transport chain. Thus, we expect to find consistent patterns of isotopic
      signatures associated with this gradient. Earlier studies on leaves of Fagus
      sylvatica, Glycine max, and Saccharum officinarum showed that the organic mass
      and cellulose of major veins or petioles were consistently more positive than the
      respective fraction in leaf laminae. The objective of the current study was to
      assess whether this pattern can be detected in a greater set of plant species.
      Leaves from ten species were collected in the summer of 2006 outdoors and in
      glasshouses. Leaf laminae including small veins were separated from the major
      veins and the isotopic signatures of the organic mass, and the soluble and non
      soluble fractions were measured for laminae and veins separately. The organic
      mass, and the soluble and non-soluble fractions of leaf laminae, were depleted in
      (13)C relative to the veins in all cases. A general trend for the signature of
      organic mass being more depleted in (13)C than the soluble fraction is in
      accordance with well-known patterns of fractionation between metabolites.

PMID- 19603470
TI  - Carbon and hydrogen isotope fractionation of benzene during biodegradation under
      sulfate-reducing conditions: a laboratory to field site approach.
AB  - The microbial carbon and hydrogen isotope fractionation of benzene under sulfate
      reducing conditions was investigated within systems of increasing complexity: (i)
      batch laboratory microcosms, (ii) a groundwater-percolated column system, and
      (iii) an aquifer transect. Recent molecular biological studies indicate that, at
      least in the laboratory microcosms and the column system, benzene is degraded by
      similar bacterial communities. Carbon and hydrogen enrichment factors
      (epsilon(C), epsilon(H)) obtained from laboratory microcosms and from the column
      study varied significantly although experiments were performed under similar
      redox and temperature conditions. Thus, enrichment factors for only a single
      element could not be used to distinguish benzene degradation under sulfate
      reducing conditions from other redox conditions. In contrast, using correlation
      of changes of hydrogen vs. carbon isotope ratios (Lambda = Delta delta(2)H/Delta
      delta(13)C), similar Lambda-values were derived for the benzene biodegradation
      under sulfate-reducing conditions in all three experimental systems
      (Lambda(laboratory microcosms) = 23 +/- 5, Lambda(column) = 28 +/- 3,
      Lambda(aquifer) = 24 +/- 2), showing the robustness of the two-dimensional
      compound-specific stable isotope analysis (2D-CSIA) for elucidating distinct
      biodegradation pathways. Comparing carbon and hydrogen isotope fractionation data
      from recent studies, an overlap in Lambda-values was observed for benzene
      biodegradation under sulfate-reducing (Lambda = 23 +/- 5 to Lambda = 29 +/- 3)
      and methanogenic (Lambda = 28 +/- 1 to Lambda = 39 +/- 5) conditions, indicating
      a similar initial benzene reaction mechanism for both electron-acceptor
      conditions.

PMID- 19603471
TI  - Effect of a controlled dietary change on carbon and nitrogen stable isotope
      ratios of human hair.
AB  - The carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) stable isotope ratios of
      human hair can be used for the interpretation of dietary habits and nutritional
      status in contemporary or past populations. Although the results of bulk or
      segmental isotope ratio analysis of human hair have been used for the
      reconstruction of an individual's diet for years, only limited data of controlled
      dietary changes on the carbon and nitrogen isotopic composition of human hair are
      available. Hair of four individuals, two males and two females, who participated
      in a dietary change experiment for 28 days was segmentally analysed for
      delta(13)C and delta(15)N. The dietary change included a change from C3 to C4
      plant enriched diets and a simultaneous replacement of terrestrial animal
      products by marine products. This resulted in an increase in delta(13)C(diet) of
      +8.5 to +9.9 per thousand and in delta(15)N(diet) of +1.5 to +2.2 per thousand.
      All subjects showed significant increases in delta(13)C(hair) and
      delta(15)N(hair) during the dietary change period, although no subject reached a
      new steady state for either carbon or nitrogen. The change in delta(15)N(hair)
      was faster than the change in delta(13)C(hair) for all individuals. The magnitude
      of change of the isotopic composition during the dietary change period could be
      attributed to the degree of physical activity of the individuals, with a higher
      physical activity resulting in a faster change.

PMID- 19603472
TI  - Short-term dynamics of isotopic composition of leaf-respired CO2 upon darkening:
      measurements and implications.
AB  - Recent advances in understanding the metabolic origin and the temporal dynamics
      in delta(13)C of dark-respired CO(2) (delta(13)C(res)) have led to an increasing
      awareness of the importance of plant isotopic fractionation in respiratory
      processes. Pronounced dynamics in delta(13)C(res) have been observed in a number
      of species and three main hypotheses have been proposed: first, diurnal changes
      in delta(13)C of respiratory substrates; second, post-photosynthetic
      discrimination in respiratory pathways; and third, dynamic decarboxylation of
      enriched carbon pools during the post-illumination respiration period. Since
      different functional groups exhibit distinct diurnal patterns in delta(13)C(res)
      (ranging from 0 to 10 per thousand diurnal increase), we explored these
      hypotheses for different ecotypes and environmental (i.e. growth light)
      conditions. Mass balance calculations revealed that the effect of respiratory
      substrates on diurnal changes in delta(13)C(res) was negligible in all
      investigated species. Further, rapid post-illumination changes in delta(13)C(res)
      (30 min), which increased from 2.6 per thousand to 5 per thousand over the course
      of the day, were examined by positional (13)C-labelling to quantify changes in
      pyruvate dehydrogenase (PDH) and Krebs cycle (KC) activity. We investigated the
      origin of these dynamics with Rayleigh mass balance calculations based on
      theoretical assumptions on fractionation processes. Neither the estimated changes
      of PDH and KC, nor decarboxylation of a malate pool entirely explained the
      observed pattern in delta(13)C(res). However, a Rayleigh fractionation of (12)C
      discriminating enzymes and/or a rapid decline in the decarboxylation rate of an
      enriched substrate pool may explain the post-illumination peak in
      delta(13)C(res). These results are highly relevant since delta(13)C(res) is used
      in large-scale carbon cycle studies.

PMID- 19603473
TI  - Use of a temperature-programmable injector coupled to gas chromatography
      combustion-isotope ratio mass spectrometry for compound-specific carbon isotopic
      analysis of polycyclic aromatic hydrocarbons.
AB  - Compound-specific isotopic analysis (CSIA) can provide information about the
      origin of analysed compounds; for instance, polycyclic aromatic hydrocarbons
      (PAHs) in aerosols. This could be a valuable tool in source apportionment of
      particulate matter (PM) air pollution. Because gas chromatography-combustion
      isotope ratio mass spectrometry (GC-C-IRMS) analysis requires an amount of at
      least 10 ng of an individual PAH, a high concentration of PAHs in the injected
      extract is needed. When the concentration is low a large volume injector creates
      the possibility of introducing a satisfactory amount of individual PAHs. In this
      study a temperature-programmable injector was coupled to GC-C-IRMS and injection
      parameters (solvent level, transfer column flow, transfers time) were optimised
      using six solid aromatic compounds (anthracene, fluoranthene, pyrene,
      benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene) dissolved in n
      pentane and EPA 610 reference mixture. CSIA results for solid PAHs were compared
      with results obtained for the single components analysed by elemental analysis
      isotope ratio mass spectrometry. The injection method was validated for two
      sample injection volumes, 50 and 100 microL. This method was also compared with
      commonly used splitless injection. To be included in the study, measurements had
      to have an uncertainty lower than 0.5 per thousand for delta(VPDB)13C and a
      minimum peak height of 200 mV. The lower concentration limits at which these
      criteria were fulfilled for PAHs were 30 mg/L for 1 microL in splitless injection
      and 0.3 and 0.2 mg/L for 50 and 100 microL, respectively, in large volume
      injection.

PMID- 19603475
TI  - A continuous flow mass spectrometry technique of argon isotope measurement for
      K/Ar geochronology.
AB  - A new method for the measurement of argon isotope composition in a continuous
      flow of helium for potassium/argon geochronology is described. Extraction of
      argon from geological samples in multiple-sample holders was carried out in a
      chamber by heating with a continuous Nd-YAG laser. The extracted and pre
      concentrated argon is passed through a chromatographic capillary column in a flow
      of helium. Argon is separated from possible contaminants in the column and is
      injected through an open split into the ion source of an isotope ratio mass
      spectrometer. Measurement of the (36)Ar, (38)Ar and (40)Ar isotopes was carried
      out in dynamic mode, using a triple-collector ion detector. These experiments
      have shown that continuous flow mass spectrometry can be used for the analysis of
      radiogenic argon in picogram quantities with an accuracy that is satisfactory for
      the solution of many geochronological problems. The method of argon isotope
      measurement in a continuous flow of helium is an alternative to the measurement
      of argon isotopes in the static mode. The sensitivity and accuracy of argon
      measurement by this method are comparable with those provided by the classical
      static method. The measurement of argon isotopes in a continuous flow of helium
      is simpler and more reliable than measurement in the static mode.

PMID- 19603474
TI  - Hair protein and amino acid 13C and 15N abundances take more than 4 weeks to
      clearly prove influences of animal protein intake in young women with a habitual
      daily protein consumption of more than 1 g per kg body weight.
AB  - A high protein or meat intake might be a risk factor for metabolic disorders.
      Stable isotopic abundances (SIA) of hair can be used as biomarkers for animal
      protein intake due to characteristic isotopic patterns of food proteins. We
      investigated if an additional meat intake (M, 200 g pork fillet/day) or an
      omission of meat and meat products (NOM) can influence the natural (15)N and
      (13)C SIA within 4 weeks in hair and plasma of young women. The daily protein
      intake (means +/- SD) was 1.40 +/- 0.29, 2.25 +/- 0.35, and 1.15 +/- 0.26 g/kg at
      baseline, during M, and during NOM, respectively. At baseline the animal protein
      intake correlated with bulk SIA of hair ((15)N: R(2) = 0.416; (13)C: R(2) =
      0.664; n = 14). However, isotope ratio mass spectrometry (IRMS) analyses have not
      shown that hair and plasma SIA were changed significantly after M or NOM.
      Possible reasons were discussed. Urinary SIA were significantly lower after M
      than after NOM ((15)N: p = 0.039; (13)C: p = 0.006) and close to those of pork
      fillet. Characteristic patterns of SIA were measured in individual amino acids
      (AA) by gas chromatography/combustion isotope ratio mass spectrometry
      (GC/C/IRMS). The results confirmed considerable differences in SIA between AA
      (delta(15)N, up to 22 per thousand; delta(13)C, up to 31 per thousand). Plots of
      (15)N versus (13)C abundances in hair revealed characteristic differences between
      indispensable and dispensable AA. The intervention-dependent changes of AA
      specific SIA were not as clear as expected. Although the AA-specific SIA may
      reveal more detailed characteristics of physiological conditions, further
      methodological research is required. We suggest that the SIA of leucine can be
      potential markers of protein intake. The reliability of SIA as biomarkers of
      protein intake still have to be tested in longer lasting intervention studies in
      humans. The results may have implications in the assessment for possible benefits
      and risks of protein consumption.

PMID- 19603476
TI  - Carbon and oxygen isotope microanalysis of carbonate.
AB  - Technical modification of the conventional method for the delta(13)C and
      delta(18)O analysis of 10-30 microg carbonate samples is described. The CO(2)
      extraction is carried out in vacuum using 105% phosphoric acid at 95 degrees C,
      and the isotopic composition of CO(2) is measured in a helium flow by gas
      chromatography/isotope ratio mass spectrometry (GC/IRMS). The feed-motion of
      samples to the reaction vessel provides sequential dropping of only the samples
      (without the sample holder) into the acid, preventing the contamination of acid
      and allowing us to use the same acid to carry out very large numbers of analyses.
      The high accuracy and high reproducibility of the delta(13)C and delta(18)O
      analyses were demonstrated by measurements of international standards and
      comparison of results obtained by our method and by the conventional method. Our
      method allows us to analyze 10 microg of the carbonate with a standard deviation
      of +/-0.05 per thousand for delta(13)C and delta(18)O. The method has been used
      successfully for the analyses of the oxygen and carbon isotopic composition of
      the planktonic and benthic foraminifera in detailed palaeotemperature
      reconstructions of the Okhotsk Sea.

PMID- 19603477
TI  - Effects of active silicon uptake by rice on 29Si fractionation in various plant
      parts.
AB  - Rice (Oryza sativa L.) accumulates large amounts of silicon which improves its
      growth and health due to enhanced resistance to biotic and abiotic stresses.
      Silicon uptake and loading to xylem in rice are predominantly active processes
      performed by transporters encoded by the recently identified genes Lsi1 (Si
      influx transporter gene) and Lsi2 (Si efflux transporter gene). Silicon
      deposition in rice during translocation to upper plant tissues is known to
      discriminate against the heavier isotopes (29)Si and (30)Si, resulting in isotope
      fractionation within the plant. We analyzed straw and husk samples of rice
      mutants defective in Lsi1, Lsi2 or both for silicon content and delta(29)Si using
      isotope ratio mass spectrometry (IRMS) and compared these results with those for
      the corresponding wild-type varieties (WT). The silicon content was higher in
      husk than in straw. All the mutant rice lines showed clearly lower silicon
      content than the WT lines (4-23% Si of WT). The delta(29)Si was lower in straw
      and husk for the uptake defective mutant (lsi1) than for WT, albeit delta(29)Si
      was 0.3 per thousand higher in husk than in straw in both lines. The effect of
      defective efflux (lsi2) differed for straw and husk with higher delta(29)Si in
      straw, but lower delta(29)Si in husk while WT showed similar delta(29)Si in both
      fractions. These initial results show the potential of Si isotopes to enlighten
      the influence of active uptake on translocation and deposition processes in the
      plant.

PMID- 19603478
TI  - The search for meaning-Symptoms and transvaginal sonography screening for ovarian
      cancer: predicting malignancy.
AB  - BACKGROUND: The mortality rate of ovarian cancer is greater than that of all
      other major gynecologic malignancies. Detecting ovarian cancer at an early and
      curable stage long has been an objective of oncologists. Recently, it was
      reported that certain symptom patterns are informative for the presence of
      ovarian malignancy. In this article, the authors report on how symptoms and
      ultrasound predict ovarian malignancy. METHODS: Two hundred seventy-two women who
      were participating in annual transvaginal sonography (TVS) screening were
      selected from among 31,748 women who were enrolled. Symptom results were
      correlated with ultrasound and surgical pathology findings. RESULTS: TVS
      performed better than symptoms analysis for detecting malignancies (sensitivity,
      73.3% vs 20%), and symptoms analysis performed better for distinguishing benign
      tumors (specificity, 91.3% vs 74.4%). The use of TVS and symptoms analysis in
      series resulted in poorer identification of malignancy (sensitivity, 16.7%) but
      improved the ability to distinguish benign tumors (specificity, 97.9%). Decisions
      using either symptoms or TVS combined in parallel had small increases in
      sensitivity (+3.3%) and had coordinated, small decreases in specificity (-5.8%).
      CONCLUSIONS: Symptoms did identify ovarian malignancies, but not as well as TVS.
      The current findings indicated that: 1) tumors that are negative by both
      ultrasound and a symptoms index are likely to be benign (specificity, >97%), and
      2) adding symptoms information that has weight equal to the weight of ultrasound
      only slightly improves the discrimination of malignancy (sensitivity increase,
      +3.3%). Thus, a major benefit in discriminating malignancy was achieved through
      ultrasound, whereas the absence of symptoms in conjunction with an abnormal
      ultrasound (characterized by a low morphology index) indicated that the mass was
      benign and that surgery may not be required. Finally, informative symptoms can be
      expected to be absent in 80% of patients with ovarian malignancies.

PMID- 19603479
TI  - Exposure to high static or pulsed magnetic fields does not affect cellular
      processes in the yeast Saccharomyces cerevisiae.
AB  - We report results of a study of the effects of strong static (up to 16 T for 8 h)
      and pulsed (up to 55 T single-shot and 4 x 20 T repeated shots) magnetic fields
      on Saccharomyces cerevisiae cultures in the exponential phase of growth. In
      contrast to previous reports restricted to only a limited number of cellular
      parameters, we have examined a wide variety of cellular processes: genome-scale
      gene expression, proteome profile, cell viability, morphology, and growth,
      metabolic and fermentation activity after magnetic field exposure. None of these
      cellular activities were impaired in response to static or pulsed magnetic field
      exposure. Our results confirm and extend previous reports on the absence of
      magnetic field effects on yeast and support the hypothesis that magnetic fields
      have no impact on the transcriptional machinery and on the integrity of
      unicellular biological systems.

PMID- 19603480
TI  - Comment on Valic et al., 2009.

PMID- 19603481
TI  - Self-assembly and chiral recognition of quartz crystal microbalance chiral
      sensor.
AB  - A novel chiral sensor based on the self-assembled monolayer of (6(A)-omega
      mercaptoethylureado-6(A)-deoxy)heptakis(2,3-di-o-phenylcarbamoyl)-6(B), 6(C),
      6(D), 6(E), 6(F), 6(G)-hexa-o-phenylcarbamoyl-beta-cyclodextrin (Ph-beta-CD-SH)
      on a quartz crystal transducer for chiral recognition was set up. (R,S)-(+/-)-(3
      methoxyphenyl)ethylamine were recognized by this QCM chiral sensor with a QCM
      chiral discrimination factor of 1.33. Furthermore, UV spectroscopy was used to
      investigate the mechanism of host-guest interactions between (6(A)-azido-6(A)
      deoxy)heptakis(2,3-di-o-phenylcarbamoyl)-6(B), 6(C), 6(D), 6(E), 6(F), 6(G)-hexa
      o-phenylcarbamoyl-beta-cyclodextrin (Ph-beta-CD) and (R,S)-(+/-)-(3
      methoxyphenyl) ethylamine. The UV discrimination factor was determined to be
      0.066.

PMID- 19603482
TI  - Ultrasound-mediated synthesis of camphoric acid-based chiral salens for the
      enantioselective trimethylsilylcyanation of aldehydes.
AB  - New chiral salen ligands were prepared by the ultrasound-irradiated condensation
      of optically active (1R, 3S)-1,2,2-trimethyl-1,3-diaminocyclopentane with
      aromatic 1-hydroxyaldehydes. The ultrasound-mediated process is more convenient
      due to shorter reaction times, energy economy, and easier isolation of the
      products. The in situ formed Ti(IV)(salen) complexes, evaluated as catalysts in
      the enantioselective trimethylsilylcyanation of benzaldehyde, were found to be
      efficient for this process, originating the corresponding product in high yields
      (72-99%) and selectivities of up to 79%. The lowest energy transition states were
      determined by computational studies. These results were in qualitative agreement
      with the experimentally observed ones.

PMID- 19603483
TI  - Foreword.

PMID- 19603485
TI  - Crystal structure of ginkbilobin-2 with homology to the extracellular domain of
      plant cysteine-rich receptor-like kinases.

PMID- 19603484
TI  - Improved prediction of protein side-chain conformations with SCWRL4.
AB  - Determination of side-chain conformations is an important step in protein
      structure prediction and protein design. Many such methods have been presented,
      although only a small number are in widespread use. SCWRL is one such method, and
      the SCWRL3 program (2003) has remained popular because of its speed, accuracy,
      and ease-of-use for the purpose of homology modeling. However, higher accuracy at
      comparable speed is desirable. This has been achieved in a new program SCWRL4
      through: (1) a new backbone-dependent rotamer library based on kernel density
      estimates; (2) averaging over samples of conformations about the positions in the
      rotamer library; (3) a fast anisotropic hydrogen bonding function; (4) a short
      range, soft van der Waals atom-atom interaction potential; (5) fast collision
      detection using k-discrete oriented polytopes; (6) a tree decomposition algorithm
      to solve the combinatorial problem; and (7) optimization of all parameters by
      determining the interaction graph within the crystal environment using symmetry
      operators of the crystallographic space group. Accuracies as a function of
      electron density of the side chains demonstrate that side chains with higher
      electron density are easier to predict than those with low-electron density and
      presumed conformational disorder. For a testing set of 379 proteins, 86% of
      chi(1) angles and 75% of chi(1+2) angles are predicted correctly within 40
      degrees of the X-ray positions. Among side chains with higher electron density
      (25-100th percentile), these numbers rise to 89 and 80%. The new program
      maintains its simple command-line interface, designed for homology modeling, and
      is now available as a dynamic-linked library for incorporation into other
      software programs.

PMID- 19603487
TI  - Target domain definition and classification in CASP8.
AB  - In order to be successful CASP experiments require experimentally determined
      protein structures. These structures form the basis of the experiment. Structural
      genomics groups have provided the vast majority of these structures in recent
      editions of CASP. Before the structure prediction assessment can begin these
      target structures must be divided into structural domains for assessment purposes
      and each assessment unit must be assigned to one or more tertiary structure
      prediction categories. In CASP8 target domain boundaries were based on visual
      inspection of targets and their experimental data, and on superpositions of the
      target structures with related template structures. As in CASP7 target domains
      were broadly classified into two different categories: "template-based modeling"
      and "free modeling." Assessment categories were determined by structural
      similarity between the target domain and the nearest structural templates in the
      PDB and by whether or not related structural templates were used to build the
      models. The vast majority of the 164 assessment units in CASP8 were classified as
      template-based modeling. Just 10 target domains were defined as free modeling. In
      addition three targets were assessed in both the free modeling and template based
      categories and a subset of 50 template-based models was evaluated as part of the
      "high accuracy" subset. The targets submitted for CASP8 confirmed a trend that
      has been apparent since CASP5: targets submitted to the CASP experiments are
      becoming easier to predict.

PMID- 19603488
TI  - Towards the elucidation of molecular determinants of cooperativity in the liver
      bile acid binding protein.
AB  - Bile acid binding proteins (BABPs) are cytosolic lipid chaperones contributing to
      the maintenance of bile acid homeostasis and functional distribution within the
      cell. Liver BABPs act in parallel with ileal transporters to ensure vectorial
      transport of bile salts in hepatocytes and enterocytes, respectively. We describe
      the investigation of ligand binding to liver BABP, an essential step in the
      understanding of intracellular bile salt transport. Binding site occupancies were
      monitored in NMR titration experiments using (15)N-labelled ligand, while the
      relative populations of differently bound BABP forms were assessed by mass
      spectrometry. This site-specific information allowed the determination of
      intrinsic thermodynamic parameters and the identification of an extremely high
      cooperativity between two binding sites. Protein-observed NMR experiments
      revealed a global structural rearrangement which suggests an allosteric mechanism
      at the basis of the observed cooperativity. The view of a molecular tool capable
      of buffering against significant concentrations of free bile salts in a large
      range of solution conditions emerges from the observed pH-dependence of binding.
      We set to determine the molecular determinants of cooperativity by analysing the
      binding properties of a protein containing a mutated internal histidine. Both
      mass spectrometry and NMR experiments are consistent with an overall decreased
      binding affinity of the mutant, while the measured diffusion coefficients of
      ligand species reveal that the affinity loss concerns essentially one of the two
      binding sites. We therefore identified a mutation able to disrupt energetic
      communication functional to efficient binding and conclude that the buried
      histidine establishes contacts that stabilize the ternary complex.

PMID- 19603486
TI  - Elucidating the exact role of engineered CRABPII residues for the formation of a
      retinal protonated Schiff base.
AB  - Cellular Retinoic Acid Binding Protein II (CRABPII) has been reengineered to
      specifically bind and react with all-trans-retinal to form a protonated Schiff
      base. Each step of this process has been dissected and four residues (Lys132,
      Tyr134, Arg111, and Glu121) within the CRABPII binding site have been identified
      as crucial for imine formation and/or protonation. The precise role of each
      residue has been examined through site directed mutagenesis and crystallographic
      studies. The crystal structure of the R132K:L121E-CRABPII (PDB-3I17) double
      mutant suggests a direct interaction between engineered Glu121 and the native
      Arg111, which is critical for both Schiff base formation and protonation.

PMID- 19603489
TI  - An analysis of secular change in the human mandible over the last century.
AB  - In light of several recent investigations that have identified notable secular
      change in cranial size and morphology over the last century, the present study
      addresses its possible effects in the mandible in U.S. populations. Standard
      measurements of 407 mandibles from the Terry (Smithsonian) and Hamann-Todd
      (Cleveland Museum of Natural History) Collections, which are primarily composed
      of individuals living in the early 20th century, were compared with those of 595
      mandibles from the Forensic Anthropology Database (Tennessee), which is primarily
      composed of individuals living from the later part of the century. The t-tests
      between the two temporally-different samples by sex and race showed statistically
      significant decreases in mandibular body width and bigonial breadth as well as
      significant increases in mandibular body length in nearly all subgroups. White
      males showed the greatest amount of change, and Black females, the least.
      Overall, these findings support the conclusion that the mandible is transforming
      into a longer, narrower, more gracile bone, paralleling many of the morphological
      shifts seen in the cranium. Factors involved likely include changes in diet,
      medical care, and dental practices.

PMID- 19603490
TI  - Molecular turnover time of soil organic matter in particle-size fractions of an
      arable soil.
AB  - The composition and molecular residence time of soil organic matter (SOM) in four
      particle-size fractions (POM >200 microm, POM 63-200 microm, silt and clay) were
      determined using Curie-point pyrolysis/gas chromatography coupled on-line to mass
      spectrometry. The fractions were isolated from soils, either continuously with a
      C(3) wheat (soil (13)C value = -26.4 per thousand), or transferred to a C(4)
      maize (soil (13)C value = -20.2 per thousand) cropping system 23 years ago.
      Pyrograms contained up to 45 different pyrolysis peaks; 37 (ca. 85%) were
      identifiable compounds. Lignins and carbohydrates dominated the POM fractions,
      proteins were abundant, but lignin was (nearly) absent in the silt and clay
      fractions. The mean turnover time (MRT) for the pyrolysis products in particulate
      organic matter (POM) was generally <15 years (fast C pool) and 20-300 years
      (medium or slow C pools) in silt and clay fractions. Methylcyclopentenone
      (carbohydrate) in the clay fraction and benzene (mixed source) in the silt
      fraction exhibited the longest MRTs, 297 and 159 years, respectively. Plant
      derived organic matter was not stored in soils, but was transformed to microbial
      remains, mainly in the form of carbohydrates and proteins and held in soil by
      organo-mineral interactions. Selective preservation of plant-derived OM (i.e.
      lignin) based on chemical recalcitrance was not observed in these arable soils.
      Association/presence of C with silt or clays in soils clearly increased MRT
      values, but in an as yet unresolved manner (i.e. 'truly' stabilized, or
      potentially still 'labile' but just not accessible C).

PMID- 19603492
TI  - The four cysteines ring motif in proteins.
AB  - Disulfide bonds play fundamental roles in proteins. This work is devoted to
      highly rare motifs containing disulfide bonds. A search for four cysteines,
      forming a 16-atom membered ring (4CR) embodying two disulfide bonds, was carried
      out against all entries in the Protein Data Bank. Searching the crystallographic
      subset, only few protein molecules, all dimeric, were found to embody this
      peculiar structural feature, which establishes a covalent link between two
      different polypeptide chains. In contrast, in a peptide studied in solution by
      NMR, the four cysteines moiety includes only residues from one chain. A
      comparative analysis provided evidence for similarity and difference. It emerged
      that 4CR motif is highly rare and may serve to gain a specialized function.

PMID- 19603493
TI  - Refinement of the long-range order parameter in predicting folding rates of two
      state proteins.
AB  - Long-range order (LRO) is one of the most successful descriptors in relating the
      three-dimensional structures of proteins with their folding rates. LRO highlights
      the importance of long-range contacts (residues that are far in sequence and
      closer in the 3D structure) in determining the folding rates of proteins across
      all structural classes of proteins. In this work, we have updated the data set of
      two-state folding proteins to examine the robustness of LRO parameter and to
      assess whether any refinements are required in defining the computation of LRO.
      LRO shows a better correlation (r = -0.85) for the increased dataset with a very
      small difference in distance cut-off compared to the old data set and reinforces
      the robustness of the parameter. When the dataset was grouped into three major
      structural classes, slight refinement of the parameter (distance of separation in
      space and sequence) gave better correlations. The corresponding correlation for
      the three structural classes are r = -0.92; sequence separation 23; spatial
      distance cut-off 5.5 A for all alpha structural class, r = -0.84; sequence
      separation 43; spatial distance cut-off 7 A for all beta structural class and r =
      -0.82; sequence separation 8; spatial distance cut-off 8 A for mixed class
      proteins. It is envisaged that during the process of protein folding, formation
      of long-range contacts beyond the above sequence separation limits may play a key
      role in determining the folding rates of proteins, and this aspect is discussed
      in the light of experimental studies on the formation of interresidue contacts
      and end-to-end loops in unfolded polypeptide chains.

PMID- 19603491
TI  - Comparison of the internalization of targeted dendrimers and dendrimer-entrapped
      gold nanoparticles into cancer cells.
AB  - Dendrimer-based nanotechnology significantly advances the area of targeted cancer
      imaging and therapy. Herein, we compared the difference of surface acetylated
      fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5)
      poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold
      nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms
      of their specific internalization to FA receptor (FAR)-overexpressing cancer
      cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and
      [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless
      of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the
      two different nanostructures reveals that the surface area and the FA moiety
      distribution from the center of the geometry are slightly different. This slight
      difference may not be recognized by the FARs on the cell membrane, consequently
      leading to similar internalization kinetics. This study underlines the fact that
      metal or inorganic NPs entrapped within dendrimers interact with cells in a
      similar way to that of dendrimers lacking host NPs.

PMID- 19603494
TI  - Sequence-dependent folding and unfolding of ligand-bound purine riboswitches.
AB  - Riboswitch regulation of gene expression requires ligand-mediated RNA folding.
      From the fluorescence lifetime distribution of bound 2-aminopurine ligand, we
      resolve three RNA conformers (C(o), C(i), C(c)) of the liganded G- and A-sensing
      riboswitches from Bacillus subtilis. The ligand binding affinities, and
      sensitivity to Mg(2+), together with results from mutagenesis, suggest that C(o)
      and C(i) are partially unfolded species compromised in key loop-loop interactions
      present in the fully folded C(c). These data verify that the ligand-bound
      riboswitches may dynamically fold and unfold in solution, and reveal differences
      in the distribution of folded states between two structurally homologous purine
      riboswitches: Ligand-mediated folding of the G-sensing riboswitch is more
      effective, less dependent on Mg(2+), and less debilitated by mutation, than the A
      sensing riboswitch, which remains more unfolded in its liganded state. We propose
      that these sequence-dependent RNA dynamics, which adjust the balance of ligand
      mediated folding and unfolding, enable different degrees of kinetic
      discrimination in ligand binding, and fine-tuning of gene regulatory mechanisms.

PMID- 19603495
TI  - Spectroscopic and molecular modeling studies on the binding of the flavonoid
      luteolin and human serum albumin.
AB  - Luteolin (LUT) is a polyphenolic compound, found in a variety of fruits,
      vegetables, and seeds, which has a variety of pharmacological properties. In the
      present contribution, binding of LUT to human serum albumin (HSA), the most
      abundant carrier protein in the blood, was investigated with the aim of
      describing the binding mode and parameters of the interaction. The application of
      circular dichroism, UV-Vis absorption, fluorescence, Raman and surface-enhanced
      Raman scattering spectroscopy combined with molecular modeling afforded a clear
      picture of the association mode of LUT to HSA. Specific interactions with protein
      amino acids were evidenced. LUT was found to be associated in subdomain IIA where
      an interaction with Trp-214 is established. Hydrophobic and electrostatic
      interactions are the major acting forces in the binding of LUT to HSA. The HSA
      conformations were slightly altered by the drug complexation with reduction of
      alpha-helix and increase of beta-turns structures, suggesting a partial protein
      unfolding. Also the configuration of at least two disulfide bridges were altered.
      Furthermore, the study of molecular modeling afforded the binding geometry.

PMID- 19603496
TI  - Human tropoelastin sequence: dynamics of polypeptide coded by exon 6 in solution.
AB  - Calorimetric studies were performed on exon 6 in powdered form and in solution
      [water and 2,2,2-trifluoroethanol (TFE), a structure-inducing solvent or
      cosolvent]. Dynamic dielectric spectroscopy (DDS) analyses were realized in water
      and 20% TFE. The major role of solvent-peptide organization is evidenced with
      these techniques. Calorimetric measurements reveal the structural water
      organization around the polypeptide as well as the presence of hydrophobic
      interactions in TFE solution. Dielectric measurements showed for exon 6/water a
      decrease of relaxations times of bulk solvent implying a faster dynamics with a
      slight increase of the activation entropy, suggesting that exon 6 probably
      creates disorder within the solvent. For TFE/water mixtures, an influence of exon
      6 on its environment was seen with a relaxation associated with the exon
      6/solvent interactions reinforced by storage of 72 h. Finally, exon 6/solvent
      interactions were clearly observed with addition of TFE.

PMID- 19603497
TI  - Statins and hepatitis C virus: friend or foe?

PMID- 19603498
TI  - Abnormality of synaptic vesicular associated proteins in cerebral cortex and
      hippocampus after microwave exposure.
AB  - Studies were performed to determine the effects of microwave on synaptic vesicles
      and the expression of synaptic vesicular associated proteins including synapsin
      I, VAMP-2, syntaxin, and synaptophysin. 25 Wistar rats were exposed to microwave
      which the average power density was 30 mW/cm(2), and whole body average specific
      absorption rate was 14.1 W/kg for 5 min. Synaptosome preparations in the cerebral
      cortex and hippocampus were obtained by isotonic Percoll/sucrose discontinuous
      gradients at 6 h, 1, 3, and 7 days after radiation. The expression of synaptic
      vesicular associated proteins was measured using Western blots and image
      analysis. The interaction between VAMP-2 and syntaxin was examined by
      coimmunoprecipitation analysis. Synapsin I in the cerebral cortex were decreased
      at 3 days (P < 0.01) after radiation and in the hippocampus increased at 1 day (P
      < 0.01), decreased at 3 days (P < 0.01), increased again at 7 days (P < 0.01)
      after exposure, compared with the sham-treated controls. Synaptophysin were
      increased in 1-7 days (P < 0.01) after exposure in the cerebral cortex and
      hippocampus. VAMP-2 were decreased at 1 and 3 days (P < 0.01) and syntaxin were
      decreased in 6 h to 3 days (P < 0.01) after radiation in the cerebral cortex and
      hippocampus. The interactions between VAMP-2 and syntaxin were decreased at 3-7
      days (P < 0.01) after radiation in the cerebral cortex and hippocampus, compared
      with the sham-treated controls. These results suggest that 30 mW/cm(2) (SAR 14.1
      W/kg) microwave radiation can result in the perturbation of the synaptic vesicles
      associated proteins: synapsin I, synaptophysin, VAMP-2, and syntaxin. The
      perturbation could induce the deposit of synaptic vesicle, which might be
      relative to the dysfunction of the synaptic transmission, even the cognition
      deficit.

PMID- 19603500
TI  - Theoretical study on nonlinear optical properties of the
      Li(+)[calix[4]pyrrole]Li(-)dimer, trimer and its polymer with diffuse excess
      electrons.
AB  - The static (hyper)polarizabilities of the dimer and trimer with diffuse excess
      electrons, [Li(+)[calix[4]pyrrole]Li(-)](n), are firstly investigated by the
      DFT(B3LYP) method in detail. For the dimer and trimer, a Li atom inside each
      calix[4]pyrrole unit is ionized to form a diffuse excess electron. The results
      show that the dimer and trimer containing two and three excess electrons,
      respectively, have very large first hyperpolarizablities as 2.3 x 10(4) and 4.0 x
      10(4) au, which are 30 and 40 times larger than that of the corresponding
      [calix[4]pyrrole](n) (n = 2, 3) without Li atom. Also, beta values of dimer and
      trimer are twice and four times as large as that of monomer containing one excess
      electron. Obviously, not only excess electron but also the number of excess
      electron plays an important role in increasing the first hyperpolarizability.
      Moreover, the (hyper)polarizabilities of the [Li(+)[calix[4]pyrrole]Li(-)](n)
      polymer are investigated at ab initio level by using the elongation finite-field
      (elongation FF) method. All the oligomers of the [Li(+)[calix[4]pyrrole]Li(-)](n)
      with many excess electrons exhibit very large first hyperpolarizability and large
      second hyperpolarizability. The present investigation shows that by introducing
      several and more excess electrons into the nonlinear optical (NLO) materials will
      be an important strategy for improving their NLO properties, which will be
      helpful for design of NLO materials.

PMID- 19603501
TI  - Graph-theoretical identification of dissociation pathways on free energy
      landscapes of biomolecular interaction.
AB  - Biomolecular association and dissociation reactions take place on complicated
      interaction free energy landscapes that are still very hard to characterize
      computationally. For large enough distances, though, it often suffices to
      consider the six relative translational and rotational degrees of freedom of the
      two particles treated as rigid bodies. Here, we computed the six-dimensional free
      energy surface of a dimer of water-soluble alpha-helices by scanning these six
      degrees of freedom in about one million grid points. In each point, the relative
      free energy difference was computed as the sum of the polar and nonpolar
      solvation free energies of the helix dimer and of the intermolecular coulombic
      interaction energy. The Dijkstra graph algorithm was then applied to search for
      the lowest cost dissociation pathways based on a weighted, directed graph, where
      the vertices represent the grid points, the edges connect the grid points and
      their neighbors, and the weights are the reaction costs between adjacent pairs of
      grid points. As an example, the configuration of the bound state was chosen as
      the source node, and the eight corners of the translational cube were chosen as
      the destination nodes. With the strong electrostatic interaction of the two
      helices giving rise to a clearly funnel-shaped energy landscape, the eight lowest
      energy cost pathways coming from different orientations converge into a well
      defined pathway for association. We believe that the methodology presented here
      will prove useful for identifying low-energy association and dissociation
      pathways in future studies of complicated free energy landscapes for biomolecular
      interaction.

PMID- 19603502
TI  - On the use of symmetry in the ab initio quantum mechanical simulation of
      nanotubes and related materials.
AB  - Nanotubes can be characterized by a very high point symmetry, comparable or even
      larger than the one of the most symmetric crystalline systems (cubic, 48 point
      symmetry operators). For example, N = 2n rototranslation symmetry operators
      connect the atoms of the (n,0) nanotubes. This symmetry is fully exploited in the
      CRYSTAL code. As a result, ab initio quantum mechanical large basis set
      calculations of carbon nanotubes containing more than 150 atoms in the unit cell
      become very cheap, because the irreducible part of the unit cell reduces to two
      atoms only. The nanotube symmetry is exploited at three levels in the present
      implementation. First, for the automatic generation of the nanotube structure
      (and then of the input file for the SCF calculation) starting from a two
      dimensional structure (in the specific case, graphene). Second, the nanotube
      symmetry is used for the calculation of the mono- and bi-electronic integrals
      that enter into the Fock (Kohn-Sham) matrix definition. Only the irreducible
      wedge of the Fock matrix is computed, with a saving factor close to N. Finally,
      the symmetry is exploited for the diagonalization, where each irreducible
      representation is separately treated. When M atomic orbitals per carbon atom are
      used, the diagonalization computing time is close to Nt, where t is the time
      required for the diagonalization of each 2M x 2M matrix. The efficiency and
      accuracy of the computational scheme is documented.

PMID- 19603503
TI  - Crystal polymorphism in a carbamazepine derivative: oxcarbazepine.
AB  - Although crystal polymorphism of carbamazepine (CBZ), an anticonvulsant used to
      treat epilepsy, has been known for decades, the phenomenon has only recently been
      noted for its keto-derivative oxcarbazepine (OCB). Here it is demonstrated that
      OCB possesses at least three anhydrous polymorphs. Although all forms are
      morphologically similar, making differentiation between crystal modifications by
      optical microscopy difficult, powder X-ray diffraction, Raman spectroscopy, and
      thermomicroscopy show distinctive differences. These techniques provide an
      efficient method of distinguishing between the three polymorphs. The crystal
      structure of form II of OCB is reported for the first time and the structure of
      form I has been redetermined at low temperature. Remarkably, both the molecular
      conformation and crystal packing of form II are in excellent agreement with the
      blind prediction made in 2007.

PMID- 19603504
TI  - Novel salicylazo polymers for colon drug delivery: dissolving polymers by means
      of bacterial degradation.
AB  - Novel azo polymers were prepared for colonic drug delivery with a release
      mechanism based on structural features of azo derivatives designed for rapid
      bacterial degradation leading to soluble polymers. Two Salicylazo derivatives
      were prepared and conjugated as side chains at different ratios to methacrylic
      acid-methyl methacrylate copolymers (Eudragits). The azo compounds were designed
      to have a hydrophilic and a hydrophobic part on opposite sides of the azo bond.
      Upon reduction of the azo bonds, the hydrophobic part is released, resulting in a
      more water soluble polymer. The solubility of the polymeric films was studied
      relative to Eudragit S known to dissolve toward the end of the small intestine.
      One of the two azo derivatives prepared gave rise to polymers, which showed
      reduced solubility relative to Eudragit S. These polymers were subjected to
      reduction tests in anaerobic rat cecal suspensions by following the release of
      the hydrophobic product. Reduction rate was found to be rapid, comparable to that
      of Sulfasalazine. Studies on the azopolymeric films in anaerobic rat cecal
      suspensions, showed that these polymers dissolve faster than in sterilized
      suspensions. Solid dosage forms may be coated with these polymers to provide an
      efficient delivery system to the colon with a rapid release mechanism.

PMID- 19603505
TI  - Gravimetric measurement of momentary drying rate of spray freeze-dried powders in
      vials.
AB  - The profile of drying rate versus primary drying time for a spray freeze-dried
      trehalose aqueous solution is much different from that determined for regular
      freeze-drying. Drying rate declines very rapidly, attributed to rate-limiting
      heat transfer through the packed bed of frozen microparticles contained in a
      vial. The inter-particulate spaces appear to be the cause of this rate
      limitation. Use of either liquid nitrogen or liquid propane as a cryogenic
      produced strong differences in both SFD particle morphology and drying rate using
      trehalose, sucrose, or mannitol. The lack of any evident correlation supports the
      argument that the inter-particulate voids determine drying behavior.

PMID- 19603506
TI  - Amorphous drug-PVP dispersions: application of theoretical, thermal and
      spectroscopic analytical techniques to the study of a molecule with
      intermolecular bonds in both the crystalline and pure amorphous state.
AB  - We report the case of BMS-488043-PVP solid dispersions which when analysed using
      modulated DSC showed compliance with the Gordon-Taylor model, confirming ideal
      mixing behaviour of the two components. The nature or presence of stabilising
      interactions between drug and PVP could not be confirmed using this technique.
      Use of FT-IR, Raman and solid-state NMR spectroscopy confirmed the presence of
      stabilising hydrogen bond interactions between the drug and PVP. Similar
      interactions are present as intermolecular bonds in the crystalline and pure
      amorphous drug system. The Gordon-Taylor equation, as it is not predictive of the
      presence of intermolecular bonds such as hydrogen bonding in an amorphous
      dispersion, may underestimate the likely physical stability of solid dispersions
      which are produced and stabilised by these interactions.

PMID- 19603508
TI  - A Cre/LoxP conditional luciferase reporter transgenic mouse for bioluminescence
      monitoring of tumorigenesis.
AB  - Genetically engineered, Cre/LoxP-conditional mouse models of cancer are designed
      to investigate the genetic contributors of tumorigenesis and are well suited to
      assess therapeutic treatment responses. The capacity to serially visualize tumor
      burden in a noninvasive fashion would greatly strengthen their applications. We
      report the generation of a bioluminescent reporter strain that allows monitoring
      of tumor development in preexisting conditional mouse tumor models. We
      demonstrate that, in a Cre-dependent glioblastoma multiforme model, tumor
      initiation and progression is readily monitored over time and that luminescent
      output is related to tumor volume. Our results show that this reporter strain may
      be combined with various Cre/loxP mouse tumor models to allow for noninvasive
      longitudinal monitoring of tumor growth and therapeutic response in vivo.

PMID- 19603509
TI  - Misexpression of Gbx2 throughout the mesencephalon by a conditional gain-of
      function transgene leads to deletion of the midbrain and cerebellum in mice.
AB  - The mouse homeobox gene, Gbx2, is expressed in discreet domains in the neural
      tube and plays a key role in forebrain and hindbrain development. Previous
      studies have demonstrated that mutual inhibition between Gbx2 and Otx2, which are
      respectively expressed in the anterior and posterior parts of the neural plate,
      positions the prospective midbrain-hindbrain junction. We describe here a
      conditional Gbx2 gain-of-function transgenic mouse line, Gbx2-GOF, which
      expresses Gbx2 and red fluorescence protein, mCherry, upon Cre-mediated
      recombination. In the absence of Cre, beta-galactosidase is broadly expressed in
      mouse embryos and adult brains carrying the transgene. By combining Gbx2-GOF and
      En1(Cre) knock-in allele, we activated expression of Gbx2 and mCherry throughout
      the mesencephalon (mes) and rhombomere 1 (r1). The ectopic expression of Gbx2
      causes an anterior shift of the mes/r1 junction at embryonic day 10.5.
      Interestingly, we found that persistent expression of Gbx2 throughout the mes/r1
      region largely abolishes expression of the isthmic organizer gene Fgf8, leading
      to deletion of the midbrain and cerebellum at later stages. Our data suggest that
      the juxtaposition of the expression domains of Gbx2 and Otx2 within the mes/r1
      area is essential for the maintenance of Fgf8 expression. Furthermore, the Gbx2
      GOF transgenic line is suitable for functional study of Gbx2 during development.

PMID- 19603507
TI  - Cell adhesive affinity does not dictate primitive endoderm segregation and
      positioning during murine embryoid body formation.
AB  - The classical cell sorting experiments undertaken by Townes and Holtfreter
      described the intrinsic propensity of dissociated embryonic cells to self
      organize and reconcile into their original embryonic germ layers with
      characteristic histotypic positioning. Steinberg presented the differential
      adhesion hypothesis to explain these patterning phenomena. Here, we have
      reappraised these issues by implementing embryoid bodies to model the patterning
      of epiblast and primitive endoderm layers. We have used combinations of embryonic
      stem (ES) cells and their derivatives differentiated by retinoic acid treatment
      to model epiblast and endoderm cells, and wild-type or E-cadherin null cells to
      represent strongly or weakly adherent cells, respectively. One cell type was
      fluorescently labeled and reconstituted with another heterotypically to generate
      chimeric embryoid bodies, and cell sorting was tracked by time-lapse video
      microscopy and confirmed by immunostaining. When undifferentiated wild-type and E
      cadherin null ES cells were mixed, the resulting cell aggregates consisted of a
      core of wild-type cells surrounded by loosely associated E-cadherin null cells,
      consistent with the differential adhesion hypothesis. However, when mixed with
      undifferentiated ES cells, the differentiated primitive endoderm-like cells
      sorted to the surface to form a primitive endoderm layer irrespective of cell
      adhesive strength, contradicting the differential adhesion hypothesis. We propose
      that the primitive endoderm cells reach the surface by random movement, and
      subsequently the cells generate an apical/basal polarity that prevents reentry.
      Thus, the ability to generate epithelial polarity, rather than adhesive affinity,
      determines the surface positioning of the primitive endoderm cells.

PMID- 19603510
TI  - Capn8 promoter directs the expression of Cre recombinase in gastric pit cells of
      transgenic mice.
AB  - Gastric pit cells are high-turnover epithelial cells of the gastric mucosa. They
      secrete mucus to protect the gastric epithelium from acid and pepsin. To
      investigate the genetic mechanisms underlying the physiological functions of
      gastric pit cells, we generated a transgenic mouse line, namely, Capn8-Cre, in
      which the expression of Cre recombinase was controlled by the promoter of the
      intracellular Ca(2+)-regulated cysteine protease calpain-8. To test the tissue
      distribution and excision activity of Cre recombinase, the Capn8-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 and LacZ staining
      demonstrated that Capn8-Cre transgenic mouse expressed Cre recombinase in the
      gastric pit cells. Cre recombinase activity was also detected in the liver and
      skin tissues. These data suggest that the Capn8-Cre mouse line described here
      could be used to dissect gene function in gastric pit cells.

PMID- 19603512
TI  - A mouse model for visualization of GABA(B) receptors.
AB  - GABA(B) receptors are the G-protein-coupled receptors for the neurotransmitter
      gamma-aminobutyric acid (GABA). Receptor subtypes are based on the subunit
      isoforms GABA(B1a) and GABA(B1b), which combine with GABA(B2) subunits to form
      heteromeric receptors. Here, we used a modified bacterial artificial chromosome
      (BAC) containing the GABA(B1) gene to generate transgenic mice expressing
      GABA(B1a) and GABA(B1b) subunits fused to the enhanced green fluorescence protein
      (eGFP). We demonstrate that the GABA(B1)-eGFP fusion proteins reproduce the
      cellular expression patterns of endogenous GABA(B1) proteins in the brain and in
      peripheral tissue. Crossing the GABA(B1)-eGFP BAC transgene into the GABA(B1) (-/
      ) background restores pre and postsynaptic GABA(B) functions, showing that the
      GABA(B1)-eGFP fusion proteins substitute for the lack of endogenous GABA(B1)
      proteins. Finally, we demonstrate that the GABA(B1)-eGFP fusion proteins
      replicate the temporal expression patterns of native GABA(B) receptors in
      cultured neurons. These transgenic mice therefore provide a validated tool for
      direct visualization of native GABA(B) receptors.

PMID- 19603514
TI  - Dynamic visualization of signal transduction in living cells: from second
      messengers to kinases.
AB  - The study of signal transduction, or the highly regulated series of biochemical
      events which allow a cell to convert a given stimulus into a functional response,
      has seen a paradigm shift with a recent explosion in the number of genetically
      encoded FRET-based biosensors capable of detecting spatial and temporal
      regulation of various signaling events in living cells. The two classes of
      biosensors discussed, namely kinase activity and second messenger biosensors,
      utilize two fluorescent proteins (FP) suitable for FRET and convert a signaling
      event of interest into a conformational change in the biosensor that can be
      measured as a change in FRET between the two FPs. Individually, these biosensors
      have been used to elucidate many complex signal transduction mechanisms in
      various biological systems. However, it has become increasingly clear that it is
      often more desirable to study multiple signaling events simultaneously, allowing
      for precise correlation of the temporal profiles of multiple signaling molecules
      without the complication of cell to cell variability. With the design of
      spectrally distinct biosensors and new coimaging strategies, simultaneous imaging
      of multiple signaling events is not only possible, but has aided in mapping the
      intricate network of cellular signal transduction cascades. Furthermore, as
      aberrant signal transduction involving second messengers and kinases is
      implicated in numerous disease states, it is hopeful that these FRET-based
      biosensors and coimaging strategies can help to unravel the molecular links
      between altered signal transduction and certain disease states.

PMID- 19603511
TI  - Analysis of epigenetic alterations to chromatin during development.
AB  - Each cell within a multicellular organism has distinguishable characteristics
      established by its unique patterns of gene expression. This individual identity
      is determined by the expression of genes in a time and place-dependent manner,
      and it is becoming increasingly clear that chromatin plays a fundamental role in
      the control of gene transcription in multicellular organisms. Therefore,
      understanding the regulation of chromatin and how the distinct identity of a cell
      is passed to daughter cells during development is paramount. Techniques with
      which to study chromatin have advanced rapidly over the past decade. Development
      of high throughput techniques and their proper applications has provided us
      essential tools to understand the regulation of epigenetic phenomena and its
      effect on gene expression. Understanding the changes that occur in chromatin
      during the course of development will not only contribute to our knowledge of
      normal gene expression, but will also add to our knowledge of how gene expression
      goes awry during disease. This review opens with an introduction to some of the
      key premises of epigenetic regulation of gene expression. A discussion of
      experimental techniques with which one can study epigenetic alterations to
      chromatin during development follows, emphasizing recent breakthroughs in this
      area. We then present examples of epigenetic mechanisms exploited in the control
      of developmental cell fate and regulation of tissue-specific gene expression.
      Finally, we discuss some of the frontiers and challenges in this area of
      research.

PMID- 19603513
TI  - A novel D-glyceraldehyde-3-phosphate binding protein, a truncated albumin, with D
      glyceraldehyde-3-phosphate dehydrogenase inhibitory property.
AB  - We have purified a novel protein from mice muscle, which through N-terminal amino
      acid sequencing was identified as a truncated form of mouse albumin. The protein
      was found to be a monomer of approximately 64 kDa and located in the cytosol. The
      purified protein strongly crossreacted with commercial albumin antibody. Presence
      of this protein was observed in different mouse organs. Further biochemical
      studies as well as CD spectroscopy indicated that the protein binds D
      glyceraldehyde-3-phosphate limiting the availability of the substrate to the
      enzyme D-glyceraldehyde-3-phosphate dehydrogenase, thereby inhibiting its
      catalytic activity. The implication of this protein in the control of glycolysis
      has been discussed.

PMID- 19603515
TI  - Tissue neogenesis and STRO-1 expression in immature and mature articular
      cartilage.
AB  - This study determined the potential for neotissue formation and the role of STRO
      1+ cells in immature versus mature articular cartilage. Cartilage explants from
      immature and mature bovine knee joints were cultured for up to 12 weeks and
      stained with safranin-O, for type II collagen and STRO-1. Bovine chondrocyte
      pellet cultures and murine knee joints at the age of 2 weeks and 3 months, and
      surgically injured cartilage, were analyzed for changes in STRO-1 expression
      patterns. Results show that immature explants contained more STRO-1+ cells than
      mature explants. After 8 weeks in culture, immature explants showed STRO-1+ cell
      proliferation and newly formed tissue, which contained glycosaminoglycan and type
      II collagen. Mature cartilage explants showed only minimal cell expansion and
      neotissue formation. Pellet cultures with chondrocytes from immature cartilage
      showed increased glycosaminoglycan synthesis and STRO-1+ staining, as compared to
      pellets with mature chondrocytes. The frequency of STRO-1+ cells in murine knee
      joints significantly declined with joint maturation. Following surgical injury,
      immature explants had higher potential for tissue repair than mature explants. In
      conclusion, these findings suggest that the high percentage of STRO-1+ cells in
      immature cartilage changes with joint maturation. STRO-1+ cells have the
      potential to form new cartilage spontaneously and after tissue injury.

PMID- 19603516
TI  - Primary cilia are highly oriented with respect to collagen direction and long
      axis of extensor tendon.
AB  - Skeletal tissues adapt to their mechanical environments by modulating gene
      expression, cell metabolism, and extracellular matrix (ECM) architecture;
      however, the mechanosensory mechanisms for these processes are incompletely
      understood. Primary cilia have emerged as critical components of the cellular
      mechanosensory apparatus and have been hypothesized to participate in
      establishment of cellular and ECM orientation, but their function in skeletal
      tissues is just beginning to be examined. Here we focused on tendon, a tissue
      with an oriented matrix that is ideal for analysis of spatial relationships
      between primary cilia and the ECM. The objective of this study was to
      characterize the incidence and orientation of tenocyte primary cilia in their
      native ECM. Primary cilia, nuclei, and collagen were analyzed three-dimensionally
      in immunofluorescently labeled rat extensor tendon using multiphoton microscopy
      and semiautomated morphometry. Primary cilia were observed in 64% of tenocytes.
      The cilia were highly oriented with respect to the ECM: cilia were aligned
      parallel to the collagen fibers and the long axis of the tendon. This study
      represents the first quantification of the in situ incidence and orientation of
      primary cilia in tendon.

PMID- 19603517
TI  - Osteogenesis induced by extracorporeal shockwave in treatment of delayed
      osteotendinous junction healing.
AB  - Healing at the osteotendinous junction (OTJ) is challenging in orthopedic
      surgery. The present study aimed to test extracorporeal shockwave (ESW) in
      treatment of a delayed OTJ healing. Twenty-eight rabbits were used for
      establishing a delayed healing (DH) model at patella-patellar-tendon (PPT)
      complex after partial patellectomy for 4 weeks and then were divided into DH and
      ESW groups. In the ESW group, a single ESW treatment was given at postoperative
      week 6 to the PPT healing complex. The samples were harvested at week 8 and 12
      for radiographic and histological evaluations with seven samples for each group
      at each time point. Micro-CT results showed that new bone volume was 1.18 +/-
      0.61 mm(3) in the ESW group with no measurable new bone in the DH group at
      postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH
      group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes
      at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively.
      The accelerated osteogenesis could be explained by acceleration of endochondral
      ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with
      delayed healing with enhanced endochondral ossification process and regeneration
      of fibrocartilage zone. These findings formed a scientific basis to potential
      clinical application of ESW for treatment of delayed OTJ healing.

PMID- 19603519
TI  - Reduction of TrkB expression de novo in the adult mouse impairs epileptogenesis
      in the kindling model.
AB  - Elucidating the mechanisms of epileptogenesis in molecular terms can identify
      targets for therapies aimed at preventing epileptogenesis or limiting its
      progression. Genetic perturbations have implicated signaling by the neurotrophin,
      BDNF, and its receptor, TrkB, in limbic epileptogenesis. Whether this signaling
      is critical to epileptogenesis in the adult brain is unclear. We sought to
      determine whether reduced expression of TrkB de novo in the mature brain is
      sufficient to impair epileptogenesis in the kindling model. Treatment of adult
      Act-CreER TrkB(flox/flox) mice with tamoxifen resulted in modest reductions of
      TrkB protein expression de novo in the adult that were detected in hippocampus
      but not other brain regions. Modest reduction of hippocampal TrkB content
      inhibited epileptogenesis induced by stimulation of hippocampus or amygdala. The
      data support the conclusion that reduction of TrkB expression in hippocampus de
      novo in the mature brain impairs epileptogenesis in the kindling model. These
      findings advance TrkB and its downstream signaling pathways as attractive targets
      for limiting the progression of epileptogenesis.

PMID- 19603520
TI  - From learning to forgetting: behavioral, circuitry, and molecular properties
      define the different functional states of the recognition memory trace.
AB  - Neuropsychological analyses of amnesic patients, as well as lesion experiments,
      indicate that the temporal lobe is essential for the encoding, storage, and
      expression of object recognition memory (ORM). However, temporal lobe structures
      directly involved in the consolidation and reconsolidation of these memories are
      not yet well-defined. We report here that systemic administration of a protein
      synthesis inhibitor before or up to 4 h after training or reactivation sessions
      impairs consolidation and reconsolidation of ORM, without affecting short-term
      memory. We have also observed that ORM reconsolidation is sensitive to protein
      synthesis inhibition, independently of the ORM trace age. Using bdnf and egr-1
      gene expression analysis, we defined temporal lobe areas related to consolidation
      and reconsolidation of ORM. Training and reactivation 21 days after ORM
      acquisition sessions provoked changes in bdnf mRNA in somatosensory, perirhinal,
      and hippocampal cortices. Reactivation 2 days after the training session elicited
      changes in bdnf and egr-1 mRNA in entorhinal and prefrontal cortices, while
      reactivation 9 days post-training provoked an increase in egr-1 transcription in
      somatosensory and entorhinal cortices. The differences in activated circuits and
      in the capacity to recall the memory trace after 9 or 21 days post-training
      suggest that memory trace suffers functional changes in this period of time. All
      these results indicate that the functional state of the recognition memory trace,
      from acquisition to forgetting, can be specifically defined by behavioral,
      circuitry, and molecular properties.

PMID- 19603518
TI  - Mammalian polyamine metabolism and function.
AB  - Polyamines are ubiquitous small basic molecules that play multiple essential
      roles in mammalian physiology. Their cellular content is highly regulated and
      there is convincing evidence that altered metabolism is involvement in many
      disease states. Drugs altering polyamine levels may therefore have a variety of
      important targets. This review will summarize the current state of understanding
      of polyamine metabolism and function, the regulation of polyamine content, and
      heritable pathological conditions that may be derived from altered polyamine
      metabolism.

PMID- 19603521
TI  - Axonal sodium channel distribution shapes the depolarized action potential
      threshold of dentate granule neurons.
AB  - Intrinsic excitability is a key feature dictating neuronal response to synaptic
      input. Here we investigate the recent observation that dentate granule neurons
      exhibit a more depolarized voltage threshold for action potential initiation than
      CA3 pyramidal neurons. We find no evidence that tonic GABA currents, leak or
      voltage-gated potassium conductances, or the expression of sodium channel isoform
      differences can explain this depolarized threshold. Axonal initial segment
      voltage-gated sodium channels, which are dominated by the Na(V)1.6 isoform in
      both cell types, distribute more proximally and exhibit lower overall density in
      granule neurons than in CA3 neurons. To test possible contributions of sodium
      channel distributions to voltage threshold and to test whether morphological
      differences participate, we performed simulations of dentate granule neurons and
      of CA3 pyramidal neurons. These simulations revealed that cell morphology and
      sodium channel distribution combine to yield the characteristic granule neuron
      action potential upswing and voltage threshold. Proximal axon sodium channel
      distribution strongly contributes to the higher voltage threshold of dentate
      granule neurons for two reasons. First, action potential initiation closer to the
      somatodendritic current sink causes the threshold of the initiating axon
      compartment to rise. Second, the proximity of the action potential initiation
      site to the recording site causes somatic recordings to more faithfully reflect
      the depolarized threshold of the axon than in cells like CA3 neurons, with
      distally initiating action potentials. Our results suggest that the proximal
      location of axon sodium channels in dentate granule neurons contributes to the
      intrinsic excitability differences between DG and CA3 neurons and may participate
      in the low-pass filtering function of dentate granule neurons.

PMID- 19603522
TI  - Colocalization of somatic and meiotic double strand breaks near the Myc oncogene
      on mouse chromosome 15.
AB  - Both somatic and meiotic recombinations involve the repair of DNA double strand
      breaks (DSBs) that occur at preferred locations in the genome. Improper repair of
      DSBs during either mitosis or meiosis can lead to mutations, chromosomal
      aberration such as translocations, cancer, and/or cell death. Currently, no model
      exists that explains the locations of either spontaneous somatic DSBs or
      programmed meiotic DSBs or relates them to each other. One common class of
      tumorigenic translocations arising from DSBs is chromosomal rearrangements near
      the Myc oncogene. Myc translocations have been associated with Burkitt lymphoma
      in humans, plasmacytoma in mice, and immunocytoma in rats. Comparing the
      locations of somatic and meiotic DSBs near the mouse Myc oncogene, we
      demonstrated that the placement of these DSBs is not random and that both events
      clustered in the same short discrete region of the genome. Our work shows that
      both somatic and meiotic DSBs tend to occur in proximity to each other within the
      Myc region, suggesting that they share common originating features. It is likely
      that some regions of the genome are more susceptible to both somatic and meiotic
      DSBs, and the locations of meiotic hotspots may be an indicator of genomic
      regions more susceptible to DNA damage.

PMID- 19603523
TI  - Are there any more ovarian tumor suppressor genes? A new perspective using ultra
      high-resolution copy number and loss of heterozygosity analysis.
AB  - Ovarian cancer is characterized by complex genetic alterations, including copy
      number loss and copy number-neutral loss of heterozygosity (LOH). These
      alterations are assumed to represent the "second hit" of the underlying tumor
      suppressor gene (TSG), however, relative to the number of LOH hotspots reported,
      few ovarian TSGs have been identified. We conducted a high-resolution LOH
      analysis using SNP arrays (500K and SNP6.0) of 106 primary ovarian tumors of
      various histological subtypes together with matching normal DNA. LOH was detected
      in at least 35% of samples on chromosomes 17, 19p, 22q, Xp, 13q, 8p, 6q, 4q, 5q,
      1p, 16q, and 9q with a median minimal region of overlap of only 300 kb. Subtype
      specific differences in LOH frequency were noted, particularly for mucinous
      cases. We also identified 192 somatic homozygous deletions (HDs). Recurrent HDs
      targeted known TSGs such as CDKN2A (eight samples), RB1 (five samples), and PTEN
      (three samples). Additional recurrent HDs targeted 16 candidate TSGs near minimal
      regions of LOH on chromosomes 17, 13, 8p, 5q, and X. Given the importance of HDs
      in inactivating known genes, these candidates are highly likely to be ovarian
      TSGs. Our data suggest that the poor success of previous LOH studies was due to
      the inability of previous technology to resolve complex genomic alterations and
      distinguish true LOH from allelic imbalance. This study shows that recurrent
      regions of LOH and HD frequently align with known TSGs suggesting that LOH
      analysis remains a valid approach to discovering new candidates.

PMID- 19603524
TI  - Genome-wide high-resolution analysis of DNA copy number alterations in NF1
      associated malignant peripheral nerve sheath tumors using 32K BAC array.
AB  - Neurofibromatosis Type I (NF1) is an autosomal dominant disorder characterized by
      the development of both benign and malignant tumors. The lifetime risk for
      developing a malignant peripheral nerve sheath tumor (MPNST) in NF1 patients is
      approximately 10% with poor survival rates. To date, the molecular basis of MPNST
      development remains unclear. Here, we report the first genome-wide and high
      resolution analysis of DNA copy number alterations in MPNST using the 32K
      bacterial artificial chromosome microarray on a series of 24 MPNSTs and three
      neurofibroma samples. In the benign neurofibromas, apart from loss of one copy of
      the NF1 gene and copy number polymorphisms, no other changes were found. The
      profiles of malignant samples, however, revealed specific loss of chromosomal
      regions including 1p35-33, 1p21, 9p21.3, 10q25, 11q22-23, 17q11, and 20p12.2 as
      well as gain of 1q25, 3p26, 3q13, 5p12, 5q11.2-q14, 5q21-23, 5q31-33, 6p23-p21,
      6p12, 6q15, 6q23-q24, 7p22, 7p14-p13, 7q21, 7q36, 8q22-q24, 14q22, and 17q21-q25.
      Copy number gains were more frequent than deletions in the MPNST samples (62% vs.
      38%). The genes resident within common regions of gain were NEDL1 (7p14), AP3B1
      (5q14.1), and CUL1 (7q36.1) and these were identified in >63% MPNSTs. The most
      frequently deleted locus encompassed CDKN2A, CDKN2B, and MTAP genes on 9p21.3
      (33% cases). These genes have previously been implicated in other cancer
      conditions and therefore, should be considered for their therapeutic, prognostic,
      and diagnostic relevance in NF1 tumorigenesis.

PMID- 19603525
TI  - Genomic aberrations in 80 cases of primary glioblastoma multiforme: Pathogenetic
      heterogeneity and putative cytogenetic pathways.
AB  - Screening the whole glioblastoma multiforme (GBM) genome for aberrations is a
      good starting point when looking for molecular markers that could potentially
      stratify patients according to prognosis and optimal treatment. We investigated
      80 primary untreated GBM using both G-banding analysis and high-resolution
      comparative genomic hybridization (HR-CGH). Abnormal karyotypes were found in 83%
      of the tumors. The most common numerical chromosome aberrations were +7, -10, 
      13, -14, -15, +20, and -22. Structural abnormalities most commonly involved
      chromosomes 1 and 3, and the short arm of chromosome 9. HR-CGH verified these
      findings and revealed additional frequent losses at 1p34-36, 6q22-27, and 19q12
      13 and gains of 3q26 and 12q13-15. Although most karyotypes and gain/loss
      patterns were complex, there was also a distinct subset of tumors displaying
      simple karyotypic changes only. There was a statistically significant association
      between trisomy 7 and monosomy 10, and also between +7/-10 as putative primary
      aberrations and secondary losses of 1p, 9p, 13q, and 22q. The low number of
      tumors in the rarer histological tumor subgroups precludes definite conclusions,
      but there did not seem to be any clear-cut cytogenetic-pathological correlations,
      perhaps with the exception of ring chromosomes in giant cell glioblastomas. Our
      findings demonstrate that although GBM is a pathogenetically very heterogeneous
      group of diseases, distinct genomic aberration patterns exist.

PMID- 19603526
TI  - Effect of 1alpha,25-dihydroxyvitamin D3 in embryonic hippocampal cells.
AB  - Although the role of 1alpha,25-dihydroxyvitamin D3 in calcium homeostasis of bone
      tissue is clear, evidence of the involvement of vitamin D3 in the central nervous
      system functions is increasing. In fact, vitamin D3 regulates vitamin D receptor
      and nerve growth factor expression, modulates brain development, and reverses
      experimental autoimmune encephalomyelitis. Only few studies, however, address
      vitamin D3 effect on embryonic hippocampal cell differentiation. In this
      investigation, the HN9.10e cell line was used as experimental model; these cells,
      that are a somatic fusion product of hippocampal cells from embryonic day-18
      C57BL/6 mice and N18TG2 neuroblastoma cells, show morphological and cytoskeletal
      features similar to their neuronal precursors. By this model, we have studied the
      time course of vitamin D3 localization in the nucleus and its effect on proteins
      involved in proliferation and/or differentiation. We found that the translocation
      of vitamin D3 from cytoplasm to the nucleus is transient, as the maximal nuclear
      concentration is reached after 10 h of incubation with (3)H-vitamin D3 and
      decreases to control values by 12 h. The appearance of differentiation markers
      such as Bcl2, NGF, STAT3, and the decrease of proliferation markers such as
      cyclin-1 and PCNA are late events. Moreover, physiological concentrations of
      vitamin D3 delay cell proliferation and induce cell differentiation of embryonic
      cells characterized by modification of soma lengthening and formation of axons
      and dendrites.

PMID- 19603528
TI  - Blockade of insulin-like growth factor-I has complex effects on structural
      plasticity in the hippocampus.
AB  - Physical exercise enhances adult neurogenesis in the hippocampus. Running induces
      the uptake of blood insulin-like growth factor-I (IGF-I) into the brain. A causal
      link between these two phenomena has been reported; running-induced increases in
      adult neurogenesis can be blocked by peripheral infusion of anti-IGF-I. Running
      also alters other aspects of hippocampal structure, including dendritic spine
      density. It remains unclear, however, whether these effects are also mediated
      through an IGF-I mechanism. To examine this possibility, we blocked peripheral
      IGF-I and examined adult neurogenesis and dendritic spine density in treadmill
      running mice. Two weeks of running resulted in an increase in cell proliferation
      in the dentate gyrus (DG) as well as an increase in dendritic spine density on DG
      granule cells and basal dendrites of CA1 pyramidal neurons, while having no
      effect on apical or basal dendritic spine density of CA3 pyramidal neurons. IGF-I
      blockade reduced cell proliferation in both sedentary and running mice, but by
      contrast, this treatment had no effect on granule cell or CA3 pyramidal cell
      dendritic spine density in sedentary or running mice. However, IGF-I antibody
      treatment seemed to prevent the running-induced increase in spine density on
      basal dendrites of CA1 pyramidal cells. These results suggest that IGF-I exerts a
      complex influence over hippocampal structure and that its effects are not
      restricted to those induced by running.

PMID- 19603527
TI  - Identifying the molecular signature of the interstitial deletion 7q subgroup of
      uterine leiomyomata using a paired analysis.
AB  - Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women,
      have recurrent cytogenetic abnormalities including interstitial deletion of 7q.
      To develop a molecular signature, matched del(7q) and non-del(7q) tumors
      identified by FISH or karyotyping from 11 women were profiled with expression
      arrays. Our analysis using paired t tests demonstrates this matched design is
      critical to eliminate the confounding effects of genotype and environment that
      underlie patient variation. A gene list ordered by genome-wide significance
      showed enrichment for the 7q22 target region. Modification of the gene list by
      weighting each sample for percent of del(7q) cells to account for the mosaic
      nature of these tumors further enhanced the frequency of 7q22 genes. Pathway
      analysis revealed two of the 19 significant functional networks were associated
      with development and the most represented pathway was protein ubiquitination,
      which can influence tumor development by stabilizing oncoproteins and
      destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the
      only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1.
      Combining the aCGH data with the del(7q) UL mosaicism-weighted expression
      analysis resulted in a list of genes that are commonly deleted and whose copy
      number is correlated with significantly decreased expression. These genes include
      the proliferation inhibitor HPB1, the loss of expression of which has been
      associated with invasive breast cancer, as well as the mitosis integrity
      maintenance tumor suppressor RINT1. This study provides a molecular signature of
      the del(7q) UL subgroup and will serve as a platform for future studies of tumor
      pathogenesis.

PMID- 19603529
TI  - Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in
      asthmatic children.
AB  - Exhaled nitric oxide (FeNO), a measure of airway inflammation, is being explored
      as a tool to guide asthma management in children. Investigators have identified
      associations of genetic polymorphisms in nitric oxide synthase genes (NOS1 and
      NOS3) with FeNO levels; however, none have explored whether these polymorphisms
      modify the relationship of environmental exposures with FeNO. The objective of
      this project was to evaluate the association of NOS polymorphisms and
      environmental exposures with FeNO levels among children with asthma. We conducted
      a 12-month prospective cohort study of 225 tobacco-smoke exposed children (6-12
      years) with doctor-diagnosed asthma. We assessed environmental exposures
      (tobacco, indoor allergens, & airborne particulates), polymorphisms in NOS1 (an
      intronic AAT tandem repeat) and NOS3 (G894T), and FeNO levels. There was no
      association of NOS1 or NOS3 polymorphisms with FeNO levels. There were no
      significant interactions of environmental exposures and the NOS1 polymorphism
      with FeNO levels. In contrast, there was an interaction of the NOS3 polymorphism
      and airborne nicotine concentration with FeNO levels (P = 0.01). Among GG
      genotype individuals, nicotine exposure did not affect FeNO levels; however,
      among individuals with at least one T allele, higher nicotine exposure was
      associated with lower FeNO levels (approximately 5 ppb decrease from the lowest
      to the highest quartile). We conclude that genetic differences may explain some
      of the conflicting results in studies of the effects of tobacco smoke exposure on
      FeNO levels and may make FeNO interpretation difficult for a subset of children
      with asthma.

PMID- 19603531
TI  - Very low prevalence of asthma and allergies in schoolchildren from rural Beijing,
      China.
AB  - BACKGROUND: The prevalence of asthma is relatively low in the Chinese population.
      There is consistent evidence that growing up on a farm is associated with
      protection against the subsequent development of asthma. OBJECTIVE: To compare
      the prevalence of asthma in schoolchildren from urban and rural China and to
      assess the possible protection associated with agricultural and livestock
      farming. METHODS: Random samples of schoolchildren aged 13-14 years from urban
      Beijing and rural area around Beijing were studied using the International Study
      of Asthma and Allergies in Childhood (ISAAC) Phase III protocol. Subjects were
      studied by questionnaires (n = 7,077) and skin-prick tests (n = 2,126). RESULTS:
      The prevalence rates of wheeze in the past year and physicians' diagnosis of
      asthma were 1.0% and 1.1% in the rural area, and these were significantly lower
      than 7.2% and 6.3% found in the urban children (P < 0.0001). For the video
      questionnaire, only 0.3% of rural children reported wheeze in the past year
      compared with 3.1% in urban children (P < 0.0001). Atopy was 3.22 times higher in
      urban children compared with rural children (P < 0.0001). For rural
      schoolchildren, 1,453 (41%) have always been living on agricultural farms since
      birth and the prevalence rates of their asthma symptoms and atopic sensitization
      were not significantly different from those who have exposed to livestock
      farming. CONCLUSION: Using the same validated ISAAC questionnaire and objective
      skin-prick tests, the prevalence rates of asthma and atopic sensitization in
      rural Chinese children were significantly lower than urban children. Exposure to
      agricultural farming conferred the same protection as livestock farming.

PMID- 19603533
TI  - Microdeletion/duplication at the Xq28 IP locus causes a de novo
      IKBKG/NEMO/IKKgamma exon4_10 deletion in families with Incontinentia Pigmenti.
AB  - The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and
      its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP
      is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination
      between two consecutive MER67B repeats. We analyzed 91 IP females carrying the
      IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found
      two recurrent nonpathological variants of IP locus, which were also present as
      rare polymorphism in control population: the IKBKGPdel, corresponding to the
      exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates the
      exon4_10 region downstream of the normal IKBKG gene. Using quantitative DNA
      analysis and microsatellite mapping, we established that both variants might
      promote the generation of the pathological IKBKGdel. Indeed, in family IP-516,
      the exon4_10 deletion was repositioned in the same allele from the pseudogene to
      the gene, whereas in family IP-688, the MER67Bdup generated the pathological
      IKBKGdel by recombination between two direct nonadjacent MER67Bs. Moreover, we
      found an instance of somatic recombination in a MER67Bdup variant, creating the
      IKBKGdel in an IP male. Our data suggest that the IP locus undergoes
      recombination producing recurrent variants that might be "at risk" of generating
      de novo IKBKGdel by NAHR during either meiotic or mitotic division.

PMID- 19603532
TI  - The mutational spectrum of holoprosencephaly-associated changes within the SHH
      gene in humans predicts loss-of-function through either key structural
      alterations of the ligand or its altered synthesis.
AB  - Mutations within either the SHH gene or its related pathway components are the
      most common, and best understood, pathogenetic changes observed in
      holoprosencephaly patients; this fact is consistent with the essential functions
      of this gene during forebrain development and patterning. Here we summarize the
      nature and types of deleterious sequence alterations among over one hundred
      distinct mutations in the SHH gene (64 novel mutations) and compare these to over
      a dozen mutations in disease-related Hedgehog family members IHH and DHH. This
      combined structural analysis suggests that dysfunction of Hedgehog signaling in
      human forebrain development can occur through truncations or major structural
      changes to the signaling domain, SHH-N, as well as due to defects in the
      processing of the mature ligand from its pre-pro-precursor or defective post
      translation bi-lipid modifications with palmitate and cholesterol.

PMID- 19603534
TI  - Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by
      in vivo micro-CT.
AB  - Daily low-amplitude, high-frequency whole-body vibration (WBV) treatment can
      increase bone formation rates and bone volume in rodents. Its effects vary,
      however, with vibration characteristics and study design, and effects on 3D bone
      microstructure of ovariectomized animals over time have not been documented. Our
      goal was to determine the effects of WBV on tibial bone of ovariectomized, mature
      rats over time using an in vivo micro-CT scanner. Adult rats were divided into:
      ovariectomy (OVX) (n = 8), SHAM-OVX (n = 8), OVX and WBV treatment (n = 7). Eight
      weeks after OVX, rats in the vibration group were placed on a vibrating platform
      for 20 min at 0.3 g and 90 Hertz. This was done 5 days a week for six weeks,
      twice a day. Zero, 8, 10, 12 and 14 weeks after OVX, in vivo micro-CT scans were
      made (vivaCT 40, Scanco Medical AG) of the proximal and diaphyseal tibia. After
      sacrifice, all tibiae were dissected and tested in three-point bending. In the
      metaphysis between 8 to 12 weeks after OVX, WBV treatment did not alter
      structural parameters compared to the OVX group and both groups continued to show
      deterioration of bone structure. In the epiphysis, structural parameters were not
      altered. WBV also did not affect cortical bone and its bending properties. To
      summarize, no substantial effects of 6 weeks of low-magnitude, high-frequency
      vibration treatment on tibial bone microstructure and strength in ovariectomized
      rats were found.

PMID- 19603539
TI  - Gpx5 protects the family jewels.
AB  - Immature spermatozoa are vulnerable to oxidative stress after their release from
      the testes, due in part to an innate deficiency in antioxidant enzymes. The male
      reproductive tract compensates for this deficiency by secreting antioxidant
      enzymes such as glutathione peroxidase 5 (Gpx5) into the epididymal lumen. In
      this issue of the JCI, Chabory et al. examined the phenotype of Gpx5-/- mice and
      found that while deletion of this gene did not seem to affect fertility per se,
      it did influence the incidence of miscarriage and embryonic defects in mated wild
      type female mice (see the related article beginning on page 2074). Importantly,
      the appearance of these problems was age dependent and associated with signs of
      oxidative stress in the spermatozoa. These results demonstrate the key importance
      of Gpx5 as an extracellular antioxidant designed to protect maturing mammalian
      spermatozoa from oxidative stress.

PMID- 19603540
TI  - Treating MS: getting to know the two birds in the bush.
AB  - Current therapies for immune-mediated diseases, such as rheumatoid arthritis and
      MS, could represent the proverbial bird in the hand - a known entity, yet limited
      in potential. Emerging biologic therapeutics for these diseases carry with them
      the potential for known as well as unknown adverse effects. Alemtuzumab, a
      biologic that depletes leukocytes, shows great promise for the treatment of MS.
      However, a significant number of patients develop autoimmunity after treatment,
      raising the level of caution for the use of this drug. In this issue of the JCI,
      Jones et al. describe a link between IL-21 levels and alemtuzumab-associated
      autoimmunity (see the related article beginning on page 2052). They show that
      proliferation of lymphocytes in those patients with autoimmunity is higher than
      in those without autoimmunity and suggest that the lymphopenia-driven
      proliferation of T cells, in combination with higher IL-21 levels, results in
      autoimmunity. This study helps inspire new enthusiasm for making a grab for the
      proverbial two birds in the bush - representing undiscovered therapies - with
      greater confidence.

PMID- 19603541
TI  - Restraining order for dendritic cells: all quiet on the fetal front.
AB  - The paradoxical ability to launch effective immunity against pathogens while
      avoiding the horror autotoxicus of autoimmunity is one of the most remarkable
      features of the mammalian immune system. This assumes a particular evolutionary
      significance at the maternal/fetal interface, where avoidance of immune
      reactivity to the fetus is vital to the propagation of the species itself.
      Several mechanisms of suppressing maternal immunity against the fetus have been
      described. The article by Collins et al. in this issue of the JCI describes a
      novel mechanism of avoiding immune surveillance in which the migratory capacity
      of dendritic cells at the maternal/fetal interface is restrained (see the related
      article beginning on page 2062).

PMID- 19603542
TI  - CCR1 and CCR5 promote hepatic fibrosis in mice.
AB  - Hepatic fibrosis develops as a response to chronic liver injury and almost
      exclusively occurs in a proinflammatory environment. However, the role of
      inflammatory mediators in fibrogenic responses of the liver is only poorly
      understood. We therefore investigated the role of CC chemokines and their
      receptors in hepatic fibrogenesis. The CC chemokines MIP-1alpha, MIP-1beta, and
      RANTES and their receptors CCR1 and CCR5 were strongly upregulated in 2
      experimental mouse models of fibrogenesis. Neutralization of CC chemokines by the
      broad-spectrum CC chemokine inhibitor 35k efficiently reduced hepatic fibrosis,
      and CCR1- and CCR5-deficient mice displayed substantially reduced hepatic
      fibrosis and macrophage infiltration. Analysis of fibrogenesis in CCR1- and CCR5
      chimeric mice revealed that CCR1 mediates its profibrogenic effects in BM-derived
      cells, whereas CCR5 mediates its profibrogenic effects in resident liver cells.
      CCR5 promoted hepatic stellate cell (HSC) migration through a redox-sensitive,
      PI3K-dependent pathway. Both CCR5-deficient HSCs and CCR1- and CCR5-deficient
      Kupffer cells displayed strong suppression of CC chemokine-induced migration.
      Finally, we detected marked upregulation of RANTES, CCR1, and CCR5 in patients
      with hepatic cirrhosis, confirming activation of the CC chemokine system in human
      fibrogenesis. Our data therefore support a role for the CC chemokine system in
      hepatic fibrogenesis and suggest distinct roles for CCR1 and CCR5 in Kupffer
      cells and HSCs.

PMID- 19603544
TI  - The potassium sensitivity test: a new gold standard for diagnosing and
      understanding the pathophysiology of interstitial cystitis.

PMID- 19603543
TI  - Sphingosine-1-phosphate in the plasma compartment regulates basal and
      inflammation-induced vascular leak in mice.
AB  - Maintenance of vascular integrity is critical for homeostasis, and temporally and
      spatially regulated vascular leak is a central feature of inflammation.
      Sphingosine-1-phosphate (S1P) can regulate endothelial barrier function, but the
      sources of the S1P that provide this activity in vivo and its importance in
      modulating different inflammatory responses are unknown. We report here that
      mutant mice engineered to selectively lack S1P in plasma displayed increased
      vascular leak and impaired survival after anaphylaxis, administration of platelet
      activating factor (PAF) or histamine, and exposure to related inflammatory
      challenges. Increased leak was associated with increased interendothelial cell
      gaps in venules and was reversed by transfusion with wild-type erythrocytes
      (which restored plasma S1P levels) and by acute treatment with an agonist for the
      S1P receptor 1 (S1pr1). S1pr1 agonist did not protect wild-type mice from PAF
      induced leak, consistent with plasma S1P levels being sufficient for S1pr1
      activation in wild-type mice. However, an agonist for another endothelial cell Gi
      coupled receptor, Par2, did protect wild-type mice from PAF-induced vascular
      leak, and systemic treatment with pertussis toxin prevented rescue by Par2
      agonist and sensitized wild-type mice to leak-inducing stimuli in a manner that
      resembled the loss of plasma S1P. Our results suggest that the blood communicates
      with blood vessels via plasma S1P to maintain vascular integrity and regulate
      vascular leak. This pathway prevents lethal responses to leak-inducing mediators
      in mouse models.

PMID- 19603545
TI  - Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes
      and subgroups of alcoholics as key factors for understanding receptor function.
AB  - OBJECTIVES: The dopamine D2 receptor (DRD2) plays an important role in the
      reinforcing and motivating effects of ethanol. Several polymorphisms have been
      reported to affect receptor expression. The amount of DRD2, expressed in a given
      individual, is the result of the expression of both alleles, each representing a
      distinct haplotype. We examined the hypothesis that haplotypes composed of
      polymorphisms, associated with reduced receptor expression, are more frequent in
      alcoholics compared with healthy individuals. METHODS: The polymorphisms 
      141ins/del, C957T, A1385G, and TaqlA were genotyped in a case-control sample
      comprising 360 alcoholics and 368 controls, and in a family-based sample of 65
      trios. To investigate more homogenous groups, we constructed two subgroups with
      respect to age at onset and antisocial personality disorder. In addition, a
      subgroup with positive family history of alcoholism was investigated. RESULTS:
      The haplotypes I-C-G-A2 and I-C-A-A1 occurred with a higher frequency in
      alcoholics [P=0.026, odds ratio (OR): 1.340; P=0.010, OR: 1.521, respectively].
      The rare haplotype I-C-A-A2 occurred less often in alcoholics (P=0.010, OR:
      0.507), and was also less often transmitted from parents to their affected
      offspring (1 vs.7). Among the subgroups, I-C-G-A2 and I-C-A-A1 had a higher
      frequency in Cloninger 1 alcoholics (P=0.083 and 0.001, OR: 1.917, respectively)
      and in alcoholics with a positive family history (P=0.031, OR: 1.478; P=0.073,
      respectively). Cloninger 2 alcoholics had a higher frequency of the rare
      haplotype D-T-A-A2 (P<0.001, OR: 4.614) always compared with controls. In
      patients with positive family history haplotype I-C-A-A2 (P=0.004, OR: 0.209),
      and in Cloninger 1 alcoholics haplotype I-T-A-A1 (P=0.045 OR: 0.460) were less
      often present. CONCLUSION: We confirmed the hypothesis that haplotypes, which are
      supposed to induce a low DRD2 expression, are associated with alcohol dependence.
      Furthermore, supposedly high-expressing haplotypes weakened or neutralized the
      action of low-expressing haplotypes.

PMID- 19603546
TI  - The insulin/Akt pathway controls a specific cell division program that leads to
      generation of binucleated tetraploid liver cells in rodents.
AB  - The formation of polyploid cells is part of the developmental program of several
      tissues. During postnatal development, binucleated tetraploid cells arise in the
      liver, caused by failure in cytokinesis. In this report, we have shown that the
      initiation of cytokinesis failure events and the subsequent appearance of
      binucleated tetraploid cells are strictly controlled by the suckling-to-weaning
      transition in rodents. We found that daily light/dark rhythms and carbohydrate
      intake did not affect liver tetraploidy. In contrast, impairment of insulin
      signaling drastically reduced the formation of binucleated tetraploid cells,
      whereas repeated insulin injections promoted the generation of these liver cells.
      Furthermore, inhibition of Akt activity decreased the number of cytokinesis
      failure events, possibly through the mammalian target of rapamycin signaling
      complex 2 (mTORC2), which indicates that the PI3K/Akt pathway lies downstream of
      the insulin signal to regulate the tetraploidization process. To our knowledge,
      these results are the first demonstration in a physiological context that insulin
      signaling through Akt controls a specific cell division program and leads to the
      physiologic generation of binucleated tetraploid liver cells.

PMID- 19603547
TI  - Mice that exclusively express TLR4 on endothelial cells can efficiently clear a
      lethal systemic Gram-negative bacterial infection.
AB  - Recognition of LPS by TLR4 on immune sentinel cells such as macrophages is
      thought to be key to the recruitment of neutrophils to sites of infection with
      Gram-negative bacteria. To explore whether endothelial TLR4 plays a role in this
      process, we engineered and imaged mice that expressed TLR4 exclusively on
      endothelium (known herein as EndotheliumTLR4 mice). Local administration of LPS
      into tissue induced comparable neutrophil recruitment in EndotheliumTLR4 and wild
      type mice. Following systemic LPS or intraperitoneal E. coli administration, most
      neutrophils were sequestered in the lungs of wild-type mice and did not
      accumulate at primary sites of infection. In contrast, EndotheliumTLR4 mice
      showed reduced pulmonary capillary neutrophil sequestration over the first 24
      hours; as a result, they mobilized neutrophils to primary sites of infection,
      cleared bacteria, and resisted a dose of E. coli that killed 50% of wild-type
      mice in the first 48 hours. In fact, the only defect we detected in
      EndotheliumTLR4 mice was a failure to accumulate neutrophils in the lungs
      following intratracheal administration of LPS; this response required TLR4 on
      bone marrow-derived immune cells. Therefore, endothelial TLR4 functions as the
      primary intravascular sentinel system for detection of bacteria, whereas bone
      marrow-derived immune cells are critical for pathogen detection at barrier sites.
      Nonendothelial TLR4 contributes to failure to accumulate neutrophils at primary
      infection sites in a disseminated systemic infection.

PMID- 19603548
TI  - Staphylococcus aureus activates type I IFN signaling in mice and humans through
      the Xr repeated sequences of protein A.
AB  - The activation of type I IFN signaling is a major component of host defense
      against viral infection, but it is not typically associated with immune responses
      to extracellular bacterial pathogens. Using mouse and human airway epithelial
      cells, we have demonstrated that Staphylococcus aureus activates type I IFN
      signaling, which contributes to its virulence as a respiratory pathogen. This
      response was dependent on the expression of protein A and, more specifically, the
      Xr domain, a short sequence-repeat region encoded by DNA that consists of
      repeated 24-bp sequences that are the basis of an internationally used
      epidemiological typing scheme. Protein A was endocytosed by airway epithelial
      cells and subsequently induced IFN-beta expression, JAK-STAT signaling, and IL-6
      production. Mice lacking IFN-alpha/beta receptor 1 (IFNAR-deficient mice), which
      are incapable of responding to type I IFNs, were substantially protected against
      lethal S. aureus pneumonia compared with wild-type control mice. The profound
      immunological consequences of IFN-beta signaling, particularly in the lung, may
      help to explain the conservation of multiple copies of the Xr domain of protein A
      in S. aureus strains and the importance of protein A as a virulence factor in the
      pathogenesis of staphylococcal pneumonia.

PMID- 19603550
TI  - Curcumin prevents and reverses murine cardiac hypertrophy.

PMID- 19603549
TI  - Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial
      fibrillation in mice.
AB  - A trial fibrillation (AF), the most common human cardiac arrhythmia, is
      associated with abnormal intracellular Ca2+ handling. Diastolic Ca2+ release from
      the sarcoplasmic reticulum via "leaky" ryanodine receptors (RyR2s) is
      hypothesized to contribute to arrhythmogenesis in AF, but the molecular
      mechanisms are incompletely understood. Here, we have shown that mice with a
      genetic gain-of-function defect in Ryr2 (which we termed Ryr2R176Q/+ mice) did
      not exhibit spontaneous AF but that rapid atrial pacing unmasked an increased
      vulnerability to AF in these mice compared with wild-type mice. Rapid atrial
      pacing resulted in increased Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      phosphorylation of RyR2, while both pharmacologic and genetic inhibition of
      CaMKII prevented AF inducibility in Ryr2R176Q/+ mice. This result suggests that
      AF requires both an arrhythmogenic substrate (e.g., RyR2 mutation) and enhanced
      CaMKII activity. Increased CaMKII phosphorylation of RyR2 was observed in atrial
      biopsies from mice with atrial enlargement and spontaneous AF, goats with lone
      AF, and patients with chronic AF. Genetic inhibition of CaMKII phosphorylation of
      RyR2 in Ryr2S2814A knockin mice reduced AF inducibility in a vagotonic AF model.
      Together, these findings suggest that increased RyR2-dependent Ca2+ leakage due
      to enhanced CaMKII activity is an important downstream effect of CaMKII in
      individuals susceptible to AF induction.

PMID- 19603552
TI  - Length variation in the N-terminal domain of the recombination-activating gene 1
      (RAG1) across squamates.

PMID- 19603553
TI  - On the passing of Thomas E. Andreoli.

PMID- 19603554
TI  - Organizational improvement: healthcare and the aging work force.

PMID- 19603551
TI  - DRG-targeted helper-dependent adenoviruses mediate selective gene delivery for
      therapeutic rescue of sensory neuronopathies in mice.
AB  - Dorsal root ganglion (DRG) neuron dysfunction occurs in a variety of sensory
      neuronopathies for which there are currently no satisfactory treatments. Here we
      describe the development of a strategy to target therapeutic genes to DRG neurons
      for the treatment of these disorders. We genetically modified an adenovirus (Ad)
      to generate a helper virus (HV) that was detargeted for native adenoviral tropism
      and contained DRG homing peptides in the adenoviral capsid fiber protein; we used
      this HV to generate DRG-targeted helper-dependent Ad (HDAd). In mice, intrathecal
      injection of this HDAd produced a 100-fold higher transduction of DRG neurons and
      a markedly attenuated inflammatory response compared with unmodified HDAd. We
      also injected HDAd encoding the beta subunit of beta-hexosaminidase (Hexb) into
      Hexb-deficient mice, a model of the neuronopathy Sandhoff disease. Delivery of
      the DRG-targeted HDAd reinstated neuron-specific Hexb production, reversed
      gangliosidosis, and ameliorated peripheral sensory dysfunction. The development
      of DRG neuron-targeted HDAd with proven efficacy in a preclinical model may have
      implications for the treatment of sensory neuronopathies of diverse etiologies.

PMID- 19603555
TI  - Molecular phylogenetics and biogeography of the Neocellia Series of Anopheles
      mosquitoes in the Oriental Region.
AB  - Molecular studies of population divergence and speciation across the Oriental
      Region are sparse, despite the region's high biodiversity and extensive Pliocene
      and Pleistocene environmental change. A molecular phylogenetic study of the
      Neocellia Series of Anopheles mosquitoes was undertaken to identify patterns of
      diversification across the Oriental Region and to infer the role of Pleistocene
      and Pliocene climatic change. A robust phylogeny was constructed using CO2 and
      ND5 mitochondrial genes and ITS2 and D3 nuclear ribosomal markers. Bayesian
      analysis of mitochondrial genes was used to date divergence events. The repeated
      contraction and expansion of forest habitat resulting from Pleistocene climatic
      fluctuations appears to have had a substantial impact on intraspecific
      diversification, but has not driven speciation within this group. Primarily early
      to mid Pliocene speciation was detected within the Annularis Group, whereas
      speciation within the Maculatus and Jamesii Groups occurred during the mid and
      late Pliocene. Both allopatric divergence driven by late Pliocene environmental
      changes and ecological adaptation, involving altitudinal replacement and
      seasonality, are likely to have influenced speciation in the Maculatus Group.

PMID- 19603557
TI  - A letter from Seleucia (Cilicia) dated 21 July 1137.

PMID- 19603556
TI  - An aberrant prostate antigen-specific immune response causes prostatitis in mice
      and is associated with chronic prostatitis in humans.
AB  - Chronic prostatitis is a common disease of unclear etiology and has no specific
      treatment. Mice deficient in the expression of the autoimmune regulator (Aire)
      gene, which are defective in thymic expression of self antigens and central
      tolerance, develop spontaneous prostatitis. In this study, we found that Aire
      deficient mice developed spontaneous B and T cell immune responses to a prostate
      autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be
      novel. We show that thymic expression of this self antigen was Aire dependent.
      Moreover, prostatitis was induced in WT mice through immunization with SVS2,
      demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The
      clinical relevance of this antigen was highlighted by our observation that
      patients with chronic prostatitis possessed specific autoantibodies against the
      human SVS2-like seminal vesicle protein semenogelin. These results provide direct
      evidence that spontaneous chronic prostatitis is an autoimmune disease and is
      regulated by both central and peripheral tolerance. Moreover, SVS2 and
      semenogelin are among the relevant autoantigens in mice and humans, respectively.

PMID- 19603558
TI  - The hospice of the Knights of St. John in Akko.

PMID- 19603559
TI  - Radiological aspects of the mummies of ancient Egyptians in the Rijksmuseum van
      Oudheden, Leiden.

PMID- 19603560
TI  - The lives of the saints as sources of data for the history of Byzantine medicine
      in the sixth and seventh centuries.

PMID- 19603561
TI  - A thirteenth-century medical case history in miniatures.

PMID- 19603562
TI  - Medieval medical miniatures in central and eastern European collections: three
      months of search behind the Iron Curtain.

PMID- 19603563
TI  - The Bartons: physicians of the north country.

PMID- 19603564
TI  - The humanitarianism of Jonathan Knight, M.D.: a principal founder of the American
      Medical Association.

PMID- 19603565
TI  - The civil rights activities of three great negro physicians (1840-1940).

PMID- 19603566
TI  - An immigrant co-operative medicine program in the South, 1887-1963.

PMID- 19603567
TI  - Healing wounds in long-term care.

PMID- 19603568
TI  - Medical theory in Heraclides of Pontus.

PMID- 19603569
TI  - Accurate assessment of stage II pressure ulcers.

PMID- 19603570
TI  - Partners in care.

PMID- 19603571
TI  - The face of dedication. Interview by Chimere G Holmes.

PMID- 19603572
TI  - Vitamin D deficiency: shining new light on the sun nutrient.

PMID- 19603573
TI  - Proliferating hope.

PMID- 19603574
TI  - Alcohol taxation policy in Australia: public health imperatives for action.
      Comment.

PMID- 19603575
TI  - Can we really hope to control healthcare spending?

PMID- 19603576
TI  - Discover the microbes within! The HHMI Wolbachia Project.

PMID- 19603577
TI  - Bioinformatics and systems biology.

PMID- 19603578
TI  - DNA and general PCR methods: PCR primer design.

PMID- 19603579
TI  - CAEP C4 sepsis guidelines.

PMID- 19603580
TI  - Scientific impact and clinical impact.

PMID- 19603581
TI  - Are one-step adhesives easier to use and better performing? Multifactorial
      assessment of contemporary one-step self-etching adhesives.
AB  - PURPOSE: The objective of this study was to examine whether one-step self-etching
      adhesives (1-SEAs) really have an advantage over multistep systems. MATERIALS AND
      METHODS: Nine one-step self-etching adhesives (Absolute, Adper Prompt L-Pop,
      Clearfil S3 Bond, G-Bond, Hybrid Bond, iBond, One-up Bond F Plus, Optibond All-in
      one and Xeno III) were included in this study. One two-step self-etching adhesive
      (Clearfil SE Bond) and one three-step etch-and-rinse adhesive (Optibond FL)
      served as controls. Their microtensile bond strength to bur-cut enamel and dentin
      was determined using a standardized protocol and the respective adhesive/dentin
      interface of these adhesives was characterized by transmission electron
      microscopy. Statistical analysis was performed with the Kruskal-Wallis
      nonparametric test. RESULTS: Regarding bond strength, the control adhesives
      tended to perform superior to the one-step adhesives. However, a significant
      difference between the control adhesives and some one-step adhesives could not
      always be demonstrated, partly due to the statistical setup of this study.
      Interface analysis by electron microscopy showed wide variation among the one
      step adhesives, depending on their composition and their acidity. 1-SEAs also
      exhibited two different kinds of droplets, depending on their hydrophilicity.
      Hydrophobic HEMA-free 1-SEAs such as G-Bond were prone to phase separation, while
      especially HEMA-containing hydrophilic 1-SEAs, such as Clearfil S3 Bond and Xeno
      III were predisposed to forming osmosis-induced droplets. Hybrid bond, Absolute,
      and iBond featured both phase separation as well as osmosis. Optibond All-in-one
      exhibited a clustering reaction of the filler particles upon solvent evaporation.
      All adhesives including the control adhesives showed signs of nanoleakage,
      indicating that all adhesives are to some extent permeable to water. A definitive
      conclusion with regard to quantitative assessment of nanoleakage was much
      hindered by inconsistencies in the silver deposition. The application procedure
      of some 1-SEAs sometimes proved as elaborate and time consuming as those of the
      two-step adhesive Clearfil SE Bond. CONCLUSION: Considering bond strength and
      application procedure, 1-SEAs are not always a better alternative to multistep
      adhesives.

PMID- 19603582
TI  - Influence of chlorhexidine concentration on the durability of etch-and-rinse
      dentin bonds: a 12-month in vitro study.
AB  - PURPOSE: To investigate the effect of 0.2% and 2% chlorhexidine (CHX) used as a
      therapeutic primer on the long-term bond strengths of two etch-and-rinse adhesive
      systems. MATERIALS AND METHODS: Adper Scotchbond 1XT (SB1) and XP-Bond (XPB) were
      evaluated. Etched dentin substrates were assigned to 6 treatment groups: (1) 0.2%
      CHX + SB1; (2) 2% CHX + SB1; (3) SB1 (control); (4) 0.2% CHX + XPB; (5) 2% CHX +
      XPB; (6) XPB (control). Composite buildups were made and beams prepared for
      microtensile bond strength testing. Beams were divided into 3 subgroups and
      either immediately pulled to failure or stored in artificial saliva for 6 or 12
      months prior to testing. Data were evaluated with three-way ANOVA. Additional
      adhesive interfaces were prepared to investigate nanoleakage expression by TEM.
      RESULTS: SB1 and XPB showed similar immediate bond strength values with or
      without CHX pretreatment (p > 0.05). After 12 months, bonds fell from 43.9 +/-
      9.5 MPa to 20.1 +/- 5.4 MPa and from 39.6 +/- 9.4 MPa to 14.2 +/- 5.0 MPa in
      control specimens for SB1 and XPB respectively, while bond fell only from 41.9 +/
      9.6MPa to 33.2 +/- 8.3 MPa and 38.3 +/- 8.9 MPa to 26.5 +/- 10.9 (for SB1 and
      XPB, respectively) when 0.2% CHX was previously used. CHX concentration did not
      affect bond strength values (0.2% vs 2%, p > 0.05). Nanoleakage increased during
      aging in controls, but reduced silver deposits were found in CHX-treated
      specimens. CONCLUSION: Chlorhexidine significantly reduced the loss of bond
      strength seen in control bonds. Since no bacterial growth was present in the
      aging conditions, the results of this study suggest that endogenous factors
      thought to degrade the adhesive interface can be inhibited by CHX. Further in
      vivo trials should confirm the role of CHX in bond durability.

PMID- 19603583
TI  - Damage accumulation simulations in the adhesive of enamel/ceramic interface using
      the FE submodelling and the element deactivation approaches.
AB  - PURPOSE: To investigate the micromechanics and damage accumulation of the
      enamel/adhesive interface using sub-modelling and element deactivation methods.
      MATERIALS AND METHODS: A finite element (FE) macromodel of the
      enamel/adhesive/ceramic interface subjected to shear bond testing was generated
      for mechanical analysis. The FE micromodel was constructed at the upper
      enamel/adhesive interface where stress concentration was found. The morphology of
      the micromechanical interlockings at the bonded interface was assigned based on a
      scanning electron micrograph. Boundary conditions of the micromodel were
      determined from the macromodel's results. Furthermore, an iterative code with the
      element deactivation method was used to calculate the microdamage accumulation.
      Parallel experiments were performed to validate the simulation. RESULTS: The
      micromodel results demonstrated that stress concentration within the adhesive
      mainly occurred at the upper corner near the enamel/adhesive interface and the
      base of the resin tags. A simulated fracture path was found at the base of the
      resin tags along the enamel/adhesive interface. The morphological observation of
      fracture patterns obtained from in vitro testing corresponded with the simulation
      results. CONCLUSION: This study showed that the FE submodelling and the element
      deactivation approaches could better simulate the micromechanical responses and
      the microdamage accumulation noted at the enamel/adhesive interface.

PMID- 19603584
TI  - Comparative radiopacity of bonding agents.
AB  - PURPOSE: The present study was undertaken to determine the content and the
      constituent elements of inorganic fillers as well as the radiopacity of 15
      recently introduced bonding agents and to compare their radiodensities with those
      of enamel and dentin by using a transmission photodensitometer. MATERIALS AND
      METHODS: The content of inorganic fillers was determined by the ashing method. In
      addition, x-ray microanalysis was used to identify the constituent elements of
      the inorganic fillers. In the measurement of the radiopacity, specimens 10 mm in
      diameter and 0.9 mm in thickness were fabricated from the 15 different bonding
      agents (n = 3 each) for a total of 45 specimens. Human premolars were
      longitudinally sectioned into 1.0-mm-thick slices to include both enamel and
      dentin, then ground to final thickness of 0.9 mm. The optical densities of
      enamel, dentin, the bonding agents, and an aluminum (Al) step wedge were obtained
      from radiographic images by transmission photodensitometry. The Al equivalent
      (mm) for each material was calculated by using the linear regression equation of
      the log of the normalized optical density and Al thickness (mm) obtained from the
      step wedge. A linear regression of the logarithm of the normalized optical
      density and Al thickness (mm) was plotted. RESULTS: The inorganic filler content
      ranged from 0.0 wt% to 43.5 wt%. Silicon and aluminum were the main constituent
      elements of the inorganic fillers; however, the resins contained different kinds
      of inorganic fillers. These elements have high and low atomic numbers. The
      surface reaction type pre-reacted glass-ionomer (S-PRG)-filled bonding agent
      (FII) had a filler content of 43.5 wt% and contained B, Si, Sr, Na, F and Al as
      its elemental constituents. The relative radiopacities expressed as equivalent
      thickness of Al were ranked ordinally. Fourteen of the 15 adhesive resins had
      radiopacity values that fell below that value for dentin, whereas the FII resin
      showed a radiopacity that was equal to or greater than that of dentin but below
      that of enamel (p < 0.05). CONCLUSION: The radiopacity of bonding agents depended
      on their filler content and the presence of heavier atoms of elements in the
      filler.

PMID- 19603585
TI  - Effect of solvent removal on adhesive properties of simplified etch-and-rinse
      systems and on bond strengths to dry and wet dentin.
AB  - PURPOSE: This study evaluated the resin-dentin microtensile bond strength
      (microTBS) of ethanol/water- (Single Bond, [SB] 3M ESPE), ethanol- (Optibond Solo
      Plus, [OP] Kerr) and acetone-based (One-Step, [OS] Bisco) two-step etch-and-rinse
      adhesives in the presence or absence of their respective solvents to dry and wet
      dentin. The ultimate tensile strength (UTS) and the degree of conversion (DC) of
      the materials were also evaluated. MATERIALS AND METHODS: Solvent-based and
      solvent-free adhesives were vigorously applied to occlusal dentin surfaces after
      phosphoric acid etching. Composite crowns were built up incrementally. After 24-h
      water storage, the specimens were sectioned in x and y directions to obtain
      bonded sticks (1.0 mm2) which were immediately tested in tension (0.5 mm/min).
      The data were analyzed by three-way ANOVA and Tukey's test (alpha = 0.05). For
      the UTS measurement, hourglass-shaped specimens of adhesives were prepared and
      tested in tension. FTIR analysis was used to verify the DC of adhesives. The data
      from UTS and FTIR was analyzed by two-way ANOVA and Tukey's test (alpha = 0.05).
      RESULTS: High microTBS values were obtained for SB and OS, regardless of the
      presence or absence of solvents or the moisture condition of dentin. A lower
      microTBS mean was observed for the solvent-free OP compared to its solvent-based
      version. Significantly higher UTS values were obtained for all adhesives after
      removal of solvents. The DC of OS in the solvent-based condition was lower than
      SB and OP. After removal of solvents, only OS showed a significant increase in
      the DC. CONCLUSION: The presence of solvents was not essential for SB and OS to
      achieve high bond strength values to both dry and wet dentin when applied under
      vigorous application.

PMID- 19603586
TI  - In vitro microleakage of composite restorations prepared by Er:YAG/Er,Cr:YSGG
      lasers and conventional drills associated with two adhesive systems.
AB  - PURPOSE: The objective of this in vitro study was to compare the degree of
      microleakage of composite restorations performed by lasers and conventional
      drills associated with two adhesive systems. MATERIALS AND METHODS: Sixty bovine
      teeth were divided into 6 groups (n = 10). The preparations were performed in
      groups 1 and 2 with a high-speed drill (HD), in groups 3 and 5 with Er:YAG laser,
      and in groups 4 and 6 with Er,Cr:YSGG laser. The specimens were restored with
      resin composite associated with an etch-and-rinse two-step adhesive system
      (Single Bond 2 [SB]) (groups 1, 3, 4) and a self-etching adhesive (One-Up Bond F
      [OB]) (groups 2, 5, 6). After storage, the specimens were polished, thermocycled,
      immersed in 50% silver nitrate tracer solution, and then sectioned
      longitudinally. The specimens were placed under a stereomicroscope (25X) and
      digital images were obtained. These were evaluated by three blinded evaluators
      who assigned a microleakage score (0 to 3). The original data were submitted to
      Kruskal-Wallis and Mann-Whitney statistical tests. RESULTS: The occlusal/enamel
      margins demonstrated no differences in microleakage for all treatments (p >
      0.05). The gingival/dentin margins presented similar microleakage in cavities
      prepared with Er:YAG, Er,Cr:YSGG, and HD using the etch-and-rinse two-step
      adhesive system (SB) (p > 0.05); otherwise, both Er:YAG and Er,Cr:YSGG lasers
      demonstrated lower microleakage scores with OB than SB adhesive (p < 0.05).
      CONCLUSION: The microleakage score at gingival margins is dependent on the
      interaction of the hard tissue removal tool and the adhesive system used. The
      self-etching adhesive system had a lower microleakage score at dentin margins for
      cavities prepared with Er:YAG and Er,Cr:YSGG than the etch-and-rinse two-step
      adhesive system.

PMID- 19603587
TI  - Microtensile bond strength of prehybridized dentin: storage time and surface
      treatment effects.
AB  - PURPOSE: This study evaluated the effect of surface treatments of the
      prepolymerized adhesive layer in the immediate dentin sealing technique (IDS) on
      the microtensile bond strength of two-step etch-and-rinse adhesive systems.
      MATERIALS AND METHODS: The occlusal dentin surfaces of 60 human third molars were
      exposed and Adper Single Bond 2 (SB) or Prime & Bond NT (PB) adhesive systems
      were applied (control groups). Immediately afterwards, the temporary cement
      RelyXTemp NE was applied on the bonded dentin surface, and the teeth were stored
      in artificial saliva for 48 h or 4 months. After the storage time, the temporary
      cement layer was removed and the following surface treatments were applied:
      aluminum oxide (AO), 37% phosphoric acid (PA), or AO+PA. Next, a second adhesive
      layer was applied for each adhesive system, and a composite resin block
      restoration (Z250) was built. The specimens were cut and submitted to
      microtensile strength (microTBS) testing. The adhesive layer thickness (ALT) was
      evaluated in other specimens from all groups by SEM. The fracture pattern was
      evaluated in all sticks tested by SEM. microTBS and ALT values were analyzed with
      two-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: The highest microTBS,
      similar to the control, was obtained with aluminum oxide and phosphoric acid
      (AO+PA) for both adhesives systems. The use of aluminum oxide alone (AO) or
      associated with phosphoric acid (AO+PA) showed values close to those of the
      control groups in relation to the ALT. The failure pattern was the same for
      control groups and AO +PA groups. CONCLUSION: Dentin prehybridization can improve
      the adhesive bond strength if the bonded surface is treated with airborne
      aluminum oxide particle abrasion associated with 37% phosphoric acid, followed by
      application of a second adhesive layer.

PMID- 19603588
TI  - Long-term evaluation of the sealing ability of two root canal sealers in
      combination with self-etching bonding agents.
AB  - PURPOSE: To compare the short- and long-term sealing ability of root canal
      fillings consisting of AH-26 and laterally compacted gutta-percha in combination
      with a self-etching dentin bonding system and the Epiphany-Resilon system.
      MATERIALS AND METHODS: Ninety-eight single-rooted human teeth were used in this
      study. The root canals were prepared using the step-back technique. Sodium
      hypochlorite 5% was used as the irrigant solution. The teeth were divided into 4
      groups. In groups 1, 3, and 4, irrigation with ethylene diamine tetracetic acid
      (EDTA) 15% was used to remove the smear layer. In the specimens of all groups, a
      final irrigation with 5 ml distilled water was performed. In groups 1 and 2, the
      Nanobond bonding system was used. The specimens in groups 1 to 3 were obturated
      with AH-26 and laterally compacted gutta-percha. In the last group (4), the
      Epiphany-Resilon system was used. Microleakage was measured at 7 days, 1 month,
      and 1 year using a fluid transport model. Two specimens from each group and 4
      where only Nanobond had been applied were prepared and examined in a scanning
      electron microscope. RESULTS: The Epiphany-Resilon system and the group obturated
      with AH-26 sealer and gutta-percha, in combination with the self-etching bonding
      system after removal of the smear layer with EDTA, demonstrated similar sealing
      ability. Kruskal-Wallis and Mann-Whitney tests showed that he results for these
      two groups were statistically significanty better than the other groups (p <
      0.05). All the groups examined showed increased apical leakage over time, but the
      increase was statistically significant after one year only in the case of the
      Epiphany-Resilon system. CONCLUSION: The use of a self-etching bonding system
      improved the sealing ability of AH-26 sealer only after removal of the smear
      layer. Significantly higher microleakage over time was only observed with the
      Epiphany-Resilon system.

PMID- 19603589
TI  - Use of the forced oscillation technique to detect bronchodilation in children:
      experience from the Schneider Children's Medical Center of Israel.
AB  - BACKGROUND: The forced oscillation technique is a noninvasive and effort
      independent technique that is well suited for lung function measurement in young
      children. FOT employs small-amplitude pressure oscillations superimposed on
      normal breathing. Therefore, it has the advantage over conventional lung function
      techniques in that it does not require patient cooperation for conducting
      respiratory maneuvers. OBJECTIVES: To test the feasibility of the FOT test in
      preschool children and to compare the results to the commonly used spirometry
      before and after the administration of bronchodilator therapy. METHODS: Forty-six
      children (median age 4.9 years, range 1.8-18.3) attending the pulmonary clinic at
      Schneider Children's Medical Center tried to perform FOT and routine spirometry.
      Results were retrospectively analyzed. RESULTS: Of the 46 children 40 succeeded
      in performing FOT and only 29 succeeded in performing simple spirometry. All but
      one of the 32 children aged 4 years and above (97%) could perform both tests.
      Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%)
      could perform spirometry. Baseline values of respiratory resistance measured at 6
      Hz (R6) negatively correlated with body length (r2 = 0.68, P < 0.005). Twenty
      four children performed both tests before and after bronchodilator therapy. A
      significant concordance was found between the measured responses to
      bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative
      response by FOT but a positive response by spirometry. CONCLUSIONS: The FOT is a
      simple, non-invasive technique that does not require subject cooperation and thus
      can be utilized for measuring lung function in children as young as 2 years old.
      Furthermore, the FOT was shown to reliably measure response to bronchodilator
      therapy.

PMID- 19603590
TI  - Adult neurotrophic factor-secreting stem cells: a potential novel therapy for
      neurodegenerative diseases.
AB  - BACKGROUND: Stem cell-based therapy is a promising approach for the treatment of
      neurodegenerative disease. In our laboratory, a novel protocol has been developed
      to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor
      secreting cells. These cells produce and secrete factors such as BDNF (brain
      derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).
      OBJECTIVE: To evaluate the migratory capacity and efficacy of NTF-SC in animal
      models of Parkinson's disease and Huntington's disease. METHODS: MSCs underwent
      two-phase medium-based induction. An efficacy study was conducted on the 6
      hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were
      transplanted on the day of 6-OHDA administration, and amphetamine-induced
      rotations were measured as a primary behavioral index. In a second experiment,
      migratory behavior was examined by transplanting cells a distance from a
      quinolinic acid-induced striatal lesion, a rat model for Huntington's disease.
      Migration, in vivo, was monitored using longitudinal magnetic resonance imaging
      scans followed by histology. RESULTS: NTF-SCs attenuated amphetamine-induced
      rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine
      depletion, post-cellular treatment. Moreover, histological assessments revealed
      that the engrafted cells migrated and acted to regenerate the damaged striatal
      dopaminergic nerve terminal network. In a preliminary work on an animal model for
      Huntington's disease, we demonstrated by high resolution MR images and
      correlating histology that induced cells migrated along the internal capsule
      towards the QA-induced lesion. CONCLUSIONS: The induced MSCs are a potential
      therapy for neurodegenerative diseases, due both to their NTF secretion and their
      ability to migrate towards the diseased tissue.

PMID- 19603591
TI  - Treatment of type 2 diabetes using meal-triggered gastric electrical stimulation.
AB  - BACKGROUND: The TANTALUS System (MetaCure Limited) is a minimally invasive
      implantable device for the treatment of type 2 diabetes. The system detects food
      intake by sensing gastric electrical variations and applies electrical
      stimulation to the gut synchronized to natural gastric activity. The system is
      commercially available in Europe and Israel and is in clinical trials in the
      United States. It has been tested in 132 patients worldwide to date. OBJECTIVES:
      To re-analyze previously reported datafrom different studies. This retrospective
      analysis of the type 2 diabetes subpopulation analyzed the expected benefit and
      characterized the significance of baseline A1c in the determination of the
      expected clinical outcome. METHODS: From the total cohort of 132 patients
      implanted with the TANTALUS device in 10 different centers in Europe and the
      U.S., we identified 50 subjects (27 females, 23 males) who were obese with
      uncontrolled T2DM on a stable regime of oral medication for 3 months prior to
      implant. This population had similar inclusion/exclusion criteria as well as
      treatment protocols and were all treated for at least 24 weeks. The analysis was
      based on the A1c change compared to baseline. RESULTS: Data after 24 weeks
      demonstrated a reduction in A1c in 80% of the patients with average drop in A1c
      of 1.1 +/- 0.1%. The average weight loss was 5.5 +/- 0.7 kg. CONCLUSIONS: The
      results suggest that the TANTALUS stimulation regime can improve glucose levels
      and induce moderate weight loss in obese T2DM patients.

PMID- 19603592
TI  - Cytokines as the major mechanism of mesenchymal stem cell clinical activity:
      expanding the spectrum of cell therapy.
AB  - Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new
      cell technology with a diverse spectrum of potential clinical applications. MSCs
      were originally conceived as stem/progenitor cells to rebuild diseased or damaged
      tissues. Over the last 14 years, since the first report of MSC infusions in
      patients, the cells have been shown to suppress graft vs. host disease, stimulate
      linear growth in a genetic disorder of bone, and foster engraftment of haplo
      identical hematopoietic stem cells. In all cases, few, if any, MSCs were
      identified at the site of clinical activity. This experience suggests a
      remarkable clinical potential, but a different general mechanism of action.
      Systemically infused MSCs seem to exert a therapeutic effect through the release
      of cytokines that act on local, or perhaps distant, target tissues. Rather than
      serving as stem cells to repair tissues, they serve as cellular factories that
      secrete mediators to stimulate the repair of tissues or elicit other beneficial
      effects. Since both the tissue source of MSCs and the ex vivo expansion system
      may significantly impact the cytokine expression profile, these parameters may be
      critically important determinants of clinical activity. Furthermore, cell
      processing protocols may be developed to optimize the cell product for a specific
      clinical indication. For example, MSC-like cells isolated from placenta and
      expanded in a three-dimensional bioreactor have recently been shown to increase
      blood flow in critical limb ischemia. Future efforts to understand the cytokine
      expression profile will undoubtedly expand the range of MSC clinical
      applications.

PMID- 19603593
TI  - Challenges and prospects for stem cell-based therapy in diabetes mellitus.

PMID- 19603594
TI  - Dr. Irmfried Eberl (1910-1948): mass murdering MD.
AB  - There are isolated cases of physicians who murdered their patients. However,
      never had a single physician personally supervised the mass murder of hundreds of
      thousands of individuals, until Dr. Irmfried Eberl. Commander of the Nazi death
      camp Treblinka, he killed both the ill and those he considered "a disease to his
      nation." At age 32 Dr. Eberl established Treblinka, where he was responsible for
      the killing of approximately 280,000 individuals within a few weeks. The position
      of camp commandant was earned following his success as head of two psychiatric
      hospitals in Germany where he coordinated the murder of thousands of mentally ill
      Jews and non-Jews within the context of the euthanasia program. However, few in
      medicine have heard of him or the harm he caused to the ethical practice of the
      profession and to human rights.

PMID- 19603595
TI  - Congenital diaphragmatic hernia: short-term outcome.
AB  - BACKGROUND: Despite progress in medical and surgical care the mortality rate of
      congenital diaphragmatic hernia remains high. Assessment of short-term outcome is
      important for comparison between different medical centers. OBJECTIVES: To
      evaluate the short-term outcome of infants born with symptomatic CDH and to
      correlate demographic and clinical parameters with short-term outcome. METHODS:
      We performed a retrospective cohort study in which demographic, obstetric and
      perinatal characteristics were extracted from infants' files. For comparison of
      categorical variables chi-square test and Fisher's exact test were used and for
      comparison of continuous variables with categorical variables the Mann-Whitney
      test was used. Sensitivity and specificity were estimated by receiver operator
      curve. RESULTS: The study group comprised 54 infants with CDH, of whom 20 (37%)
      survived the neonatal period. Demographic characteristics were not associated
      with survival. Regarding antenatal characteristics, absence of polyhydramnion and
      postnatal diagnosis were correlated with better survival. Apgar scores (above 5
      at 1 minute and 7 at 5 minutes), first arterial pH after delivery (above 7.135)
      and presence of pulmonary hypertension were significantly correlated with
      survival. Also, infants surviving up to 6 days were 10.71 times more likely to
      survive the neonatal period. CONCLUSIONS: The survival rate of symptomatic
      newborns with CDH at our center was 37% for the period 1988-2006. Prenatal
      diagnosis, Apgar score at 5 minutes and first pH after delivery were found to be
      the most significant predictors of survival. Prospective work is needed to
      evaluate the long-term outcome of infants with CDH.

PMID- 19603596
TI  - Management of clinically suspected scaphoid fractures: a survey of current
      practice in Israel.
AB  - BACKGROUND: Fracture of the scaphoid is the most common fracture of a carpal
      bone. Nevertheless, the diagnosis of SF might be challenging. Plain X-rays that
      fail to demonstrate a fracture line while clinical findings suggest the existence
      of such a fracture is not uncommon. Currently there is no consensus in the
      literature as to how a clinically suspected SF should be diagnosed, immobilized
      and treated. OBJECTIVES: To assess the current status of diagnosis and treatment
      of clinically suspected scaphoid fractures in Israeli emergency departments.
      METHODS: We conducted a telephonic survey among orthopedic surgeons working in
      Israeli EDs as to their approach to the diagnosis and treatment of occult SF.
      RESULTS: A total of 42 orthopedic surgeons in 6 hospital EDs participated in the
      survey. They reported performing a mean of 2.45 +/- 0.85 clinical tests, with
      tenderness over the snuffbox area being the sign most commonly used. A mean of
      4.38 +/- 0.76 X-ray views were ordered for patients with a clinically suspected
      SF. The most common combination included posterior-anterior, lateral,
      semipronated and semisupinated oblique views. All participating surgeons reported
      immobilizing the wrists of patients with occult fractures in a thumb spica cast
      based on their clinical findings. Upon discharge from the ED patients were
      advised to have another diagnostic examination as follows: 29 (69%) repeated X
      rays series, 18 (43%) were referred to bone scintigraphy and 2 (5%) to computed
      tomography; none were referred to magnetic resonance imaging. CONCLUSIONS: No
      consensus was found among Israeli orthopedic surgeons working in EDs regarding
      the right algorithm for assessment of clinically suspected SF. There is a need
      for better guidelines to uniformly dictate the order and set of tests to be used
      in the assessment of occult fractures.

PMID- 19603597
TI  - Sickle cell anemia in northern Israel: screening and prevention.
AB  - BACKGROUND: Sickle cell anemia is a hemolytic anemia caused by a single mutation
      in position 6 of the beta globin molecule. About 80 patients with SCA in northern
      Israel are currently receiving treatment. OBJECTIVES: To assess a screening
      program in northern Israel aimed at detecting couples at risk for having
      offspring with SCA. METHODS: Since 1987, screening for beta thalassemia in
      pregnant women in northern Israel has been conducted, and from 1999 all the
      samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.
      RESULTS: During the 20 year period 1987-2006 a total of 69,340 women were
      screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses
      were performed in couples at risk for having an offspring with Hgb S. The mean
      gestational age was 13 +/- 4 weeks. Fifty-four of those diagnoses revealed
      affected fetuses and in 4 cases the couple declined to perform therapeutic
      abortion. CONCLUSIONS: The economic burden to the health services for treating
      SCA patients is about U.S.$ 7000 per year, and the institution of prevention
      programs has proven cost-effective in populations with a high frequency of
      carriers. Since our program is aimed to also detect beta thalassemia, a disease
      that is more frequent in this area (> 2.5%), the added cost for the prevention of
      SCA is less significant despite the low incidence of the S gene in our
      population, namely < 1%.

PMID- 19603598
TI  - Cardiovascular diseases in the elderly in a consultant outpatient cardiac clinic.
AB  - BACKGROUND: The incidence of cardiovascular disease increases with age, and
      visits by elderly patients to the outpatient cardiac clinic are becoming more
      frequent. OBJECTIVES: To characterize cardiovascular pathologies of patients 70
      years of age and over who visit the outpatient cardiac clinic. METHODS: We
      investigated cardiovascular pathologies, risk factors, and medications in new
      patients over a 2 month period. RESULTS: The study population comprised 290
      patients: 139 (47.9%) were older than 70 years. Among the cardiovascular
      pathologies, aortic stenosis, angina pectoris, congestive heart failure, s/p
      coronary artery bypass graft, and stroke were more frequent in the elderly
      patients than in those under age 70. Among the risk factors for ischemic heart
      disease, only hypertension was more frequent in the elderly population, whereas
      fewer in this group were active smokers. The mean number of medications
      administered was 3.51 +/- 1.63 among the elderly patients compared to 1.99 +/-
      1.7 among the younger ones (P = 0.0001). Beta-blockers were the most frequently
      used cardiovascular drugs both in the elderly (59.7%) and in the younger patients
      (43%) (P = 0.0046). CONCLUSIONS: Patients over age 70 represent about half the
      visits in our outpatient clinic. Their multiple cardiovascular pathologies and
      therapeutic requirements raise the issue of developing the cardiology service to
      meet the special needs of geriatric patients.

PMID- 19603599
TI  - Olfaction--a window to the mind.
AB  - Although our knowledge of the brain, the olfactory sense and autoimmunity
      continues to evolve, examining the olfaction ability is not yet routinely applied
      by clinicians in the process of diagnosis and treatment. Moreover, assessment of
      the sense of smell and olfactory impairments is usually overlooked by patients
      and their clinicians. Given the clinical data reviewed here, clinicians should be
      encouraged to screen for olfactory impairments, which can help in the early
      diagnosis of CNS diseases such as Parkinson, dementia and schizophrenia, as well
      as CNS-autoimmune diseases such as neuropsychiatric lupus.

PMID- 19603600
TI  - Percutaneous aortic valve implantation: early clinical experience and future
      perspectives.
AB  - The incidence of aortic valve stenosis is growing rapidly in the elderly.
      Nonetheless, many symptomatic patients are not referred for surgery usually
      because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty
      is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues
      were the first to describe percutaneous aortic valve implantation in a patient,
      opening a new era of aortic stenosis management. In the present review we report
      a patient treated by this novel method, discuss and assess how it is implanated,
      report the findings of studies conducted to date, and suggest future directions
      for percutaneous treatment of aortic valve disease.

PMID- 19603601
TI  - Base of the tongue metastasis: aggressive behavior of triple-negative breast
      carcinoma.

PMID- 19603602
TI  - Kingella kingae prosthetic valve endocarditis complicated by a paravalvular
      abscess.

PMID- 19603603
TI  - Pneumo-hydropericardium as a complication of B chest trauma.

PMID- 19603604
TI  - Rudolf Nissen (1896-1981): his contributions to surgery and his role in Turkey.
AB  - Eminent surgeon Rudolf Nissen performed innovative studies in surgery during his
      time in Turkey, to which he fled from Germany before the Second World War. This
      paper discusses Nissen's invaluable contribution not only to Istanbul
      University's surgical department but also to the universal field of surgery.

PMID- 19603605
TI  - [The MULTISTRATEGY study].

PMID- 19603606
TI  - [The FATA study].

PMID- 19603607
TI  - [MULTISTRATEGY and FATA: merits, limits and troubles of no profit clinical trials
      in acute myocardial infarction].

PMID- 19603608
TI  - [Pulmonary arterial hypertension. Part II: Medical and surgical treatment].
AB  - Treatment of pulmonary arterial hypertension (group 1 of clinical classification)
      has been recently characterized by important progresses, particularly in
      pharmacological therapy. Only until few years ago, patients with pulmonary
      arterial hypertension were treated with non-specific drugs, such as diuretics and
      digoxin for right heart failure and calcium-channel blockers in the minority of
      cases, responders to the acute vasoreactivity test. In addition, use of oral
      anticoagulant treatment was supported by uncontrolled studies. In the last 15
      years (in particular in the last 8 years) different randomized controlled trials
      assessing the functional, clinical and hemodynamic efficacy of three classes of
      targeted drugs (prostanoids, endothelin receptor antagonists and
      phosphodiesterase type 5 inhibitors) with pulmonary vascular dilating and
      antiproliferative effects have been performed. This information has allowed the
      proposal of an evidence-based treatment algorithm. Treatment starts with general
      measures (physical activity, fertility control, respiratory tract infection,
      etc.) and supportive therapy (anticoagulant therapy, diuretics, oxygen, digoxin).
      Patients who respond to the acute vasoreactivity test (10% of idiopathic form)
      are treated with high doses of calcium-channel blockers, non-responders with
      targeted therapies either on monotherapy or combination. Usually an oral active
      drug is initiated and a second compound of a different class is combined in case
      of non-satisfactory response to the first treatment. Combination therapy should
      be performed only in specialized centers with large experience on use of targeted
      therapies and their relevant side effects. In case of failure of medical therapy,
      possible options are balloon atrial septostomy and/or listing for lung or heart
      lung transplantation. As available treatments do not constitute a cure for
      pulmonary arterial hypertension, further progresses are expected in the near
      future.

PMID- 19603609
TI  - [The prevention of infective endocarditis toward a surprising paradigm:
      antibiotic prophylaxis restricted to patients at risk of endocarditis with poor
      outcome].
AB  - The rationale for antibiotic prophylaxis of infective endocarditis is based on
      reproducible evidence of experimental infection induced by bacteremia in
      previously damaged endothelium. However, in the absence of clinical evidence from
      randomized studies, the extensive practice of antibiotic prophylaxis has recently
      been limited to high-risk cardiac conditions to prevent poor outcome infective
      endocarditis. In addition, the new paradigm for prevention of endocarditis
      requires a comprehensive approach to extracardiac risk conditions (bacterial
      virulence, comorbidity, demographic variables), which may be responsible for an
      unfavorable clinical course, independent of preexistent cardiac disease. In
      particular, prevention of nosocomial infective endocarditis deserves special
      attention over and above the periprocedural antibiotic prophylaxis suggested by
      scientific guidelines, mainly focused on community-acquired endocarditis.

PMID- 19603610
TI  - [Prophylaxis of infective endocarditis. Joint position paper of the Italian
      Federation of Cardiology and the Italian Society of Infectious and Tropical
      Diseases].

PMID- 19603611
TI  - [Iatrogenic risk of permanent pacemaker and defibrillator implantation].
AB  - The considerable evolution in technique and hardware, occurred over the past
      three decades, has greatly simplified the implantation procedure of pacemakers
      and cardioverter-defibrillators. Indeed, the introduction of relatively simple
      and safe methods of central venous access, and the miniaturization of the
      generator with subcutaneous placement have facilitated the implantation. However,
      inherent with cardiac pacing and defibrillating therapy is the potential for the
      occurrence of an early or delayed untoward event. Although skill, experience, and
      technique are all mitigating factors, every cardiologist should know potential
      complications and should be able to stratify overall risk related to a device
      implantation. Thus, both the implanting physician or the clinical cardiologist
      must be concerned not only with measures to avoid complications, but also with
      their early recognition and treatment.

PMID- 19603612
TI  - ["Dilated cardiomyopathy": an epidemic of our times].

PMID- 19603613
TI  - [Percutaneous treatment for chronic coronary occlusion: only virtuosity? Medical
      therapy and first-line treatment for chronic coronary occlusion].

PMID- 19603614
TI  - [Percutaneous treatment for chronic coronary occlusion: only virtuosity?
      Angioplasty is the first choice of treatment for chronic coronary occlusion].

PMID- 19603615
TI  - Severe epithelial keratopathy after hyperopic presbyopic photorefractive
      keratectomy.

PMID- 19603616
TI  - Retinal straylight and complaint scores 18 months after implantation of the
      AcrySof monofocal and ReSTOR diffractive intraocular lenses.
AB  - PURPOSE: To evaluate retinal straylight and patient complaint scores 18 months
      after implantation with the AcrySof ReSTOR diffractive multifocal intraocular
      lens (IOL) (Alcon Laboratories Inc). METHODS: Retinal straylight was measured
      with the C-Quant (Oculus Optikgerate GmbH) system in 40 eyes implanted with the
      AcrySof ReSTOR IOL (SA60D3) and in 40 eyes implanted with the AcrySof SA60AT
      monofocal IOL. Complaint scores were assessed by a questionnaire in both groups
      of patients at three different lighting conditions--day light, dimmed light, and
      at night. RESULTS: Seventy-five percent of eyes (30/40) of the ReSTOR group and
      80% of eyes (32/40) of the SA60AT control group showed a retinal straylight value
      within or better than the normal range. No statistically significant differences
      between groups were found (P = .790). Patients of the ReSTOR group showed
      significantly more complaint scores at all assessed lighting conditions:
      increasing factors were 1.53, 2.02, and 2.66, for day light, dimmed light, and
      night, respectively (P < .0001). Comparing the amount of straylight, the
      multifocal group had 20% more straylight, albeit not significant at the 1% level.
      CONCLUSIONS: The AcrySof ReSTOR IOL showed similar retinal straylight values
      compared to the monofocal IOL. Subjectively, patients with the diffractive IOL
      claimed significantly more glare for all light conditions, especially at night.

PMID- 19603617
TI  - Effect of iris registration on outcomes of LASIK for myopia with the VISX
      CustomVue platform.
AB  - PURPOSE: To compare visual outcomes after LASIK using the VISX STAR S4 CustomVue,
      with and without Iris Registration technology. METHODS: In this retrospective
      study, LASIK was performed on 239 myopic eyes, with or without astigmatism, of
      142 patients. Iris registration LASIK was performed on 121 eyes and non-iris
      registration LASIK was performed on 118 eyes. Primary outcome measures were
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      and manifest refraction. RESULTS: At 6 months, the mean values for UCVA (logMAR)
      were 0.00 +/- 0.09 in the iris registration group and -0.01 +/- 0.11 in the non
      iris registration group (P = .587). Seventy-nine percent of eyes in the iris
      registration group had UCVA of 20/20 or better compared to 78% in the non-iris
      registration group (P = .518). Ninety-two percent of eyes in the iris
      registration group and 90% in the non-iris registration group were within +/-
      0.50 diopters (D) of emmetropia (P = .999). Mean postoperative absolute change in
      total root-mean-square higher order aberrations in the iris registration group
      and non-iris registration group was 0.22 microm and 0.19 microm, respectively (P
      = .6). At 3 months, the mean magnitude of error of surgically induced astigmatism
      was -0.09 in the iris registration group and -0.04 in the non-iris registration
      group (P = .25). CONCLUSIONS: Wavefront-guided LASIK with the VISX STAR S4
      CustomVue laser system, independent of iris registration status, is effective,
      safe, and predictable. Under well-controlled surgical conditions, this study did
      not find any statistical significance supporting the better achievement of visual
      acuity, astigmatism correction, or the lesser induction of higher order
      aberrations using iris registration in comparison to a non-iris registration
      system.

PMID- 19603618
TI  - Combined corneal topography and corneal wavefront data in the treatment of
      corneal irregularity and refractive error in LASIK or PRK using the Carl Zeiss
      Meditec MEL 80 and CRS-Master.
AB  - PURPOSE: To assess the efficacy, safety, and accuracy of TOSCA II (Topography
      Supported Custom Ablation) treatments for the correction of high corneal
      aberrations and refractive error following previous ocular surgery. METHODS:
      Forty-eight eyes of 32 patients were included for study. Indications for TOSCA II
      treatment included small optical zone, decentered ablation, subjective visually
      significant higher order aberrations, and irregularly irregular astigmatism
      induced by LASIK, photorefractive keratectomy, radial keratotomy, conductive
      keratoplasty, cataract surgery, and deep lamellar keratoplasty. An ablation
      profile based on corneal topography data and corneal wavefront and manifest
      refraction was created using the CRS-Master software (Carl Zeiss Meditec) to
      treat corneal irregularity and refractive error simultaneously. Postoperative
      assessments were performed at 1 week and 1, 2, 3, 6, and 12 months. RESULTS: Mean
      attempted spherical equivalent refraction (SE) was -1.12 +/- 1.97 diopters (D)
      (range: +1.13 to -10.50 D). Mean attempted cylinder correction was 1.34 +/- 1.65
      D (range: 0.00 to 7.75 D). Median age was 38 years (range: 19 to 68 years).
      Median follow-up was 9.4 months. Accuracy: mean deviation from the intended SE
      correction was -0.19 +/- 0.94 D, 60% of eyes were within +/- 0.50 D and 77% of
      eyes were within +/- 1.00 D of the intended SE. Cylinder: the correction ratio
      was 1.49 +/- 0.85 and the error ratio was 0.87 +/- 0.69. EFFICACY: 56% of eyes
      achieved uncorrected visual acuity of 20/20 or better and 88% achieved 20/40 or
      better. SAFETY: 34% of eyes gained one or more lines of best spectacle-corrected
      visual acuity, 15% lost one line, and no eye lost two or more lines. Contrast
      sensitivity: for the subset of eyes with below normal contrast sensitivity
      preoperatively, there was a statistically significant improvement in contrast
      sensitivity at 3 cycles per degree (cpd), 6 cpd, and 12 cpd (P < .05). Stability:
      the average change in refraction between 3 months and 1year was +0.38 +/- 0.30 D.
      Higher order aberrations: the average higher order root-mean-square decreased by
      21% and the average spherical aberration decreased by 41%. CONCLUSIONS: The MEL
      80 CRS-Master TOSCA II software appears to be an effective treatment for
      decentrations, optical zone enlargement, and reduction of higher order
      aberrations. The refractive outcome was satisfactory after one treatment.

PMID- 19603619
TI  - Presbyopia treatment by monocular peripheral presbyLASIK.
AB  - PURPOSE: To investigate monocular peripheral presbyLASIK on the non-dominant eye
      with distance-directed monofocal refractive surgery on the dominant eye in
      treating presbyopia. METHODS: One hundred three patients underwent treatment with
      a VISX S4 system and follow-up from 1.1 to 3.9 years (mean 27.4 months). Average
      patient age was 53.3 years. Preoperative refraction ranged from -9.75 to +2.75
      diopters (D). Non-dominant eyes underwent peripheral presbyLASlK--an aspheric,
      pupil-size dependent LASIK to induce central corneal relative flattening and
      peripheral corneal relative steepening. Dominant eyes underwent monofocal
      refraction-based LASIK (75.8%), wavefront-guided LASIK, limbal relaxing
      incisions, or no treatment to optimize distance vision. RESULTS: At final follow
      up, 91.3% (94/103) of all patients, 89% (25/28) of hyperopes, and 92% (69/75) of
      myopes reported complete spectacle independence and 7.8% (8/103) used spectacles
      for less than 1 hour per week. Distance unaided visual acuity was at least 20/20
      in 67.9% (19/28) of hyperopes and 70.7% (53/75) of myopes, at least 20/20 at 80
      cm in 85.7% (24/28) of hyperopes and 84% (63/75) of myopes, and at least 20/20 at
      40 cm in 71.4% (20/28) of hyperopes and 65.3% (49/75) of myopes, PresbyLASIK
      increased overall higher order aberrations similarly to refraction-based LASIK
      for myopes but to a greater extent in hyperopic cases. PresbyLASIK WaveScan
      spherical equivalent refraction was stable in myopes but migrated an average
      +0.31 D in hyperopes over the follow-up period. CONCLUSIONS: Monocular peripheral
      presbyLASIK is a valuable option for presbyopic patients considering refractive
      surgery.

PMID- 19603620
TI  - Wavefront-guided LASIK for myopia: effect on visual acuity, contrast sensitivity,
      and higher order aberrations.
AB  - PURPOSE: To determine the impact of wavefront-guided LASIK for myopia with or
      without astigmatism on high and low contrast best spectacle-corrected visual
      acuity (BSCVA), photopic and mesopic contrast sensitivity, and higher order
      aberrations. METHODS: Bilateral wavefront-guided LASIK (LADAR-Vision4000;
      Hansatome microkeratome) was performed on 324 eyes (162 patients) with a mean
      spherical manifest refraction of -2.84 +/- 1.35 diopters (D) (range: -0.25 to 
      6.50 D) and astigmatism of -0.81 +/- 0.74 D (range: 0 to -4.00 D). Mean age was
      37.7 +/- 9.3 years (range: 20 to 60 years). Best spectacle-corrected visual
      acuity and contrast sensitivity were assessed using ETDRS charts and vertical
      sinusoidal gratings, respectively. Higher order aberrations were measured using a
      Shack-Hartmann wavefront sensor, analyzed across a 5-mm pupil. Repeated measures
      and post hoc analyses determined statistical significance (P < .0025). Only right
      eyes were analyzed. RESULTS: One hundred thirty-six eyes (84%) had uncorrected
      visual acuity of 20/20 or better 6 months postoperative; 80.9% (131 eyes) were
      within +/- 0.50 D of attempted correction. Statistically significant
      postoperative improvements were noted in high and low contrast BSCVA (both P < or
      = .001); in photopic contrast sensitivity at 3, 6, and 12 cycles per degree
      (cpd); and in mesopic contrast sensitivity at 12 and 18 cpd (all P < .001). With
      respect to higher order aberrations, a statistically significant change was seen
      in Zernike coefficients Z3(-1), Z3(1), Z3(-3), Z3(3), and Z4(4) following surgery
      (range of mean absolute change: 0.042 to 0.142 microm; all P < or = .001). All
      increased in magnitude except for Z3(-3), which decreased. CONCLUSIONS: Despite
      an increase in higher order aberrations, wavefront-guided LASIK yields excellent
      visual acuity and contrast sensitivity. Spherical aberration, which increases the
      most following non-wavefront-guided LASIK, showed no significant change.

PMID- 19603621
TI  - Agreement between Pentacam and videokeratography in corneal power assessment.
AB  - PURPOSE: To investigate agreement between a rotating Scheimpflug camera
      (Pentacam, Oculus Optikgerate GmbH) and two corneal topographers (TMS-2
      Topography System, Tomey; and Keratron Scout, Optikon 2000 SpA) in measuring the
      corneal power of normal eyes. METHODS: The mean corneal powers calculated by
      simulated keratometry (SimK) with each topographer were compared to those
      provided by the Pentacam in 71 patients. Specifically, the corneal power values
      of the Pentacam included in this analysis were the SimK (calculated using the
      measured anterior corneal radius and standard keratometric index of 1.3375) and
      the True net power (calculated using the anterior and posterior corneal
      curvatures and Gaussian optics formula for thick lenses, where the actual
      refractive index of the air, cornea, and aqueous humor are entered). Bland-Altman
      plots were used to investigate agreement and analysis of variance (ANOVA) was
      performed to detect statistical differences. RESULTS: Although ANOVA did not
      disclose a statistically significant difference among the mean SimK values (TMS
      2: 43.20 +/- 1.51 diopters [D], Keratron Scout: 43.29 +/-1.48 D, Pentacam: 43.25
      +/- 1.53 D), the 95% limits of agreement between the TMS-2 and Pentacam and
      between the Keratron Scout and Pentacam were wide (-1.05 to +0.94 D and -0.95 to
      +1.02 D, respectively). Agreement was even poorer when considering the mean True
      net power (42.00 +/- 1.54 D), which was significantly lower than the mean
      Pentacam SimK (P < .001). CONCLUSIONS: Although corneal topography and the
      Pentacam provide similar SimK values, their data should not be used
      interchangeably as only moderate agreement exists between them. Corneal power
      values calculated by the True net power are significantly lower than any SimK and
      cannot be entered into intraocular lens power formulas.

PMID- 19603622
TI  - Repeatability and reproducibility of corneal curvature measurements using the
      Pentacam and Keratron topography systems.
AB  - PURPOSE: To compare the repeatability and reproducibility of corneal curvature
      measurements using the Pentacam eye scanner (Oculus Optikgerate GmbH) and
      Keratron corneal topographer (Optikon 2000 SpA). METHODS: Axial topography maps
      were used to acquire measurements. Twenty-six eyes of 26 healthy patients were
      measured to determine repeatability and reproducibility. Another 10 eyes of 10
      healthy patients were included in a parallel study. Three measurements per eye
      were performed. Repeatability was assessed via the coefficient of variation.
      Reproducibility was assessed using Bland-Altman plots. Linear correlations were
      used to determine the agreement between devices. A P value < .05 was considered
      statistically significant. RESULTS: The majority of coefficient of variations for
      both devices were within 1%. The coefficient of variation of the Pentacam was
      higher in the superior cornea (P < .01). The mean difference (95% limits of
      agreement) in the flattest meridian between examiners was -0.03 +/- 0.27 diopters
      (D) (range: -0.56 to +0.49 D) for the Pentacam and -0.08 +/- 0.21 D (range: -0.50
      to +0.33 D) for the Keratron. The mean difference (95% limits of agreement) in
      the steepest meridian was -0.10 +/- 0.26 D (range: -0.60 to +0.41 D) for the
      Pentacam and -0.11 +/-0.22 D (range: -0.53 to +0.31 D) for the Keratron. The mean
      axial power for the central 3.0 mm of the Pentacam was statistically
      significantly lower than that of the Keratron (P < .01). CONCLUSIONS: Although
      statistically significant differences were noted, both devices provided
      repeatable and reproducible corneal measurements centrally. Pentacam
      repeatability outcomes indicate that superior corneal measurements should be
      interpreted with caution.

PMID- 19603623
TI  - A 14-year follow-up of photorefractive keratectomy.
AB  - PURPOSE: To evaluate the long-term outcome of myopic photorefractive keratectomy
      (PRK). METHODS: This prospective study included 31 patients (49 eyes) who
      underwent PRK between 1991 and 1993. A Summit UV200 excimer laser was used.
      Patients were divided into two groups--low myopia: preoperative < 6.00 diopters
      (D) (range: -1.50 to -5.75 D) (n = 19); and high myopia: preoperative > 6.00 D
      (range: -6.00 to -13.00 D) (n = 12). Long-term postoperative follow-up was every
      2 years up to 14 years. Refraction, visual acuity, corneal status, and
      intraocular pressure (IOP) were evaluated. At 14 years, corneal topography and
      endothelial cell count were performed. RESULTS: At last follow-up, manifest
      refraction spherical equivalent (MRSE) for the low myopia group was -0.17 +/-
      0.8, uncorrected visual acuity (UCVA) logMAR was -0.06 +/- 0.55, and best
      spectacle-corrected visual acuity (BSCVA) logMAR was 0.00 +/- 1.00. The high
      myopia group had a final MRSE of -0.67 +/- 1.4, UCVA logMAR -0.11 +/- 0.55, and
      BSCVA logMAR -0.03 +/- 1.00. At 14 years, BSCVA for most eyes was at least equal
      to preoperative BSCVA. In both groups, haze increased between 3 and 6 months,
      then declined in the first year. A temporary increase of IOP was seen in 4 eyes.
      Complications were minor haze (2 eyes), transient anisocoria (9 eyes), and
      intraepithelial hemosiderin deposits (4 eyes). No abnormalities in endothelial
      cell count or morphology, astigmatism, or ectasia were noted. Three patients
      reported night vision disturbance, but the majority of patients were satisfied
      with the outcome based on subjective questionnaire (low myopia group: 84%; high
      myopia group: 75%). CONCLUSIONS: Our study demonstrates the safety of myopic PRK.

PMID- 19603624
TI  - First commercial perfluorochemicals found in human blood.

PMID- 19603625
TI  - Artificial sweetener makes ideal tracer.

PMID- 19603626
TI  - Overcoming nontechnical barriers to the implementation of sustainable solutions
      in industry.
AB  - Maintaining sustainable practices will require a concert of efforts including
      industry-wide cooperation, governmental openness, and education reform.

PMID- 19603627
TI  - Estimates of upper bounds and trends in nano-TiO2 production as a basis for
      exposure assessment.
AB  - An upper bound is estimated for the magnitude of potential exposure to nano-TiO2
      with the purpose of enabling exposure assessment and, ultimately, risk assessment
      Knowledge of the existing bulk TiO2 market is combined with available nano-TiO2
      production data to estimate current nano-TiO2 sources as a baseline. The
      evolution of nano-TiO2 production as a percentage of the total TiO2 market is
      then projected based on material and market information along with a method that
      combines observations from scientific articles and patents as predictive
      indicators of the rate of innovative transformation.

PMID- 19603628
TI  - Effects of agriculture upon the air quality and climate: research, policy, and
      regulations.
AB  - Scientific assessments of agricultural air quality, including estimates of
      emissions and potential sequestration of greenhouse gases, are an important
      emerging area of environmental science that offers significant challenges to
      policy and regulatory authorities. Improvements are needed in measurements,
      modeling, emission controls, and farm operation management. Controlling emissions
      of gases and particulate matter from agriculture is notoriously difficult as this
      sector affects the most basic need of humans, i.e., food. Current policies
      combine an inadequate science covering a very disparate range of activities in a
      complex industry with social and political overlays. Moreover, agricultural
      emissions derive from both area and point sources. In the United States,
      agricultural emissions play an important role in several atmospherically mediated
      processes of environmental and public health concerns. These atmospheric
      processes affect local and regional environmental quality, including odor,
      particulate matter (PM) exposure, eutrophication, acidification, exposure to
      toxics, climate, and pathogens. Agricultural emissions also contribute to the
      global problems caused by greenhouse gas emissions. Agricultural emissions are
      variable in space and time and in how they interact within the various processes
      and media affected. Most important in the U.S. are ammonia (where agriculture
      accounts for approximately 90% of total emissions), reduced sulfur
      (unquantified), PM25 (approximately 16%), PM110 (approximately 18%), methane
      (approximately 29%), nitrous oxide (approximately 72%), and odor and emissions of
      pathogens (both unquantified). Agriculture also consumes fossil fuels for
      fertilizer production and farm operations, thus emitting carbon dioxide (CO2),
      oxides of nitrogen (NO(x)), sulfur oxides (SO(x)), and particulates. Current
      research priorities include the quantification of point and nonpoint sources, the
      biosphere-atmosphere exchange of ammonia, reduced sulfur compounds, volatile
      organic compounds, greenhouse gases, odor and pathogens, the quantification of
      landscape processes, and the primary and secondary emissions of PM. Given the
      serious concerns raised regarding the amount and the impacts of agricultural air
      emissions, policies must be pursued and regulations must be enacted in orderto
      make real progress in reducing these emissions and their associated environmental
      impacts.

PMID- 19603629
TI  - Material and energy dependence of services and its implications for climate
      change.
AB  - As the services industry has grown and diversified, there has been a rapid rise
      in the share of energy and material costs in provision of services. As a result,
      services, which have traditionally been considered immaterial by their nature,
      are now absorbing substantial amounts of energy and material goods. By
      decomposing the CO2 emissions embodied in material goods and services, this study
      quantitatively analyzes the implications of energy and materials consumption in
      services for the change in indirect CO2 emissions by household consumers in
      Japan. The results show that the domestic CO2 emissions associated with the
      energy and material goods absorbed by services through the supply chain increased
      consistently during the decade 1990-2000, thereby constituting a key element in
      the rise in CO2 emissions due to household consumption. The energy and materials
      within the supply chain underlying services that have been identified as the main
      causes of this increase include electric power consumption, petroleum products,
      building renovation and repair, distribution of printed materials, plastic
      products and water, all of which are necessary to support the services in
      question. This study highlights the increasing importance of energy and materials
      consumption by services in the context of climate change policy.

PMID- 19603630
TI  - Diurnal and seasonal variability of gasoline-related volatile organic compound
      emissions in Riverside, California.
AB  - On- and off-road mobile sources are the dominant contributors to urban
      anthropogenic volatile organic compound (AVOC) emissions. Analyses of gasoline
      samples from California for both summer and winter indicate significant
      differences in liquid fuel and vapor chemical composition due to intentional
      seasonal adjustments. Ambient concentrations of 55 VOCs were measured via in situ
      gas chromatography in the 2005 Study of Organic Aerosols at Riverside (SOAR)
      during both summer and fall. A chemical mass balance analysis was used to
      differentiate vapor pressure-driven VOC emissions from other motor vehicle
      related emissions such as tailpipe exhaust. Overall, fuel vapor emissions
      accounted for 31 +/- 2% of gasoline-related VOC in Riverside; California's
      emission factor model similarly estimates 31% of gasoline-related VOC emissions
      are fuel vapor. The diurnal pattern of vapor pressure-driven VOC source
      contributions is relatively stable around 10 microg/m3, while whole gasoline
      (i.e., tailpipe) contributions peak at approximately 60 microg/m3 during the
      morning commute. There is no peak in whole gasoline source contributions during
      the afternoon, due to rapid dilution associated with high mixing heights and wind
      speeds in the Riverside area. The relationship between estimated gasoline-related
      VOC and observed carbon monoxide concentrations in this study is similar to
      California's 2005 emission inventory; we calculated a VOC to CO mass ratio of
      0.086 +/- 0.006 (95% CI) compared to 0.097 in the emission inventory for all
      gasoline-related sources.

PMID- 19603631
TI  - Natural attenuation of arsenic by sediment sorption and oxidation.
AB  - Arsenic sorption onto aquifer sediments was investigated in anaerobic laboratory
      batch and column uptake experiments and characterized by As, Fe, and Mn X-ray
      absorption spectroscopy (XAS) to estimate the extent and mechanism of abiotic
      sorption and oxidation of As(III). Batch experiments at pH 6 showed that the
      amount of As(III) or As(V) sorption from synthetic background porewaterto
      sediments was similar as a function of total As concentration, but slightly more
      As(V) was sorbed than As(III) with increasing As concentrations. Column
      experiments with As(III) solutions in the absence and presence of dissolved Fe2+
      showed more As uptake in the presence of Fe but also more Fe desorption during
      flushout with As-free solutions such that net As uptake was similar to, or less
      than that of, the Fe-free experiment. Fits to bulk Fe X-ray absorption near-edge
      spectroscopy (XANES) spectra showed no change between unreacted and reacted
      sediments. Manganese XANES revealed small increases in absorption in the spectral
      region associated with Mn(II) after reaction, indicating sediment Mn reduction.
      However, XANES spectra showed that Mn is not present as Mn(IV)O2(s) but is
      probably substituted into other sediment minerals as a mixture of Mn(II,III).
      Quantitative analyses of As XANES spectra, which indicated mixtures of As(III)
      and As(V) after reaction with As(III) solutions, were used to estimate a fraction
      of As(V) in excess of native As(V) in the sediment (0.2 mmol kg(-1)) that
      corresponds to sorbed As(III) oxidized to As(V). The spectroscopic and solution
      data indicate that the aquifer sediments have a limited abiotic capacity to
      oxidize As(III), which did not exceed 30% of the total amount of As sorbed and
      was estimated in the range of 0.025-0.4 mmol kg-(-1) sediment. In the presence of
      dissolved Fe2+, the precipitation of Fe(III) hydrous oxide phases will be an
      effective mechanism for As scavenging only if there exists sufficient dissolved
      oxygen in groundwater to oxidize Fe. Once the aqueous oxidative capacity is
      exhausted, dissolved Fe2+ may compete with As(III) for the limited abiotic
      oxidation supplied by sediment Mn-bearing phases.

PMID- 19603632
TI  - Origins and transport of aquatic dioxins in the Japanese watershed: soil
      contamination, land use, and soil runoff events.
AB  - Significant dioxins accumulations in Japanese forests and paddy fields have been
      observed, and surface soil runoff caused by rainfall and irrigation (i.e., soil
      puddling in paddy fields) results in dioxins input into the aquatic environment.
      An extensive investigation into the origins and transport of aquatic dioxins in
      the Yasu watershed, Japan was conducted considering surface soil contamination
      level, land use, and type of soil runoff event (i.e., irrigation runoff [IR],
      rainfall runoff [RR], and base flow [BF]). Combined use of the chemically
      activated luciferase expression (CALUX) assay together with high-resolution gas
      chromatography and high-resolution mass spectrometry (HRGC/HRMS) efficiently
      enabled this study, so that origins, transport, and dynamic movement of aquatic
      dioxins in the watershed were revealed. The particulate organic carbon normalized
      particulate-dioxins WHO-toxic equivalent (TEQ) concentration predicted by the
      CALUX assay (Spar) was found to be a convenient molecular marker to indicate
      origins of aquatic dioxins and clearly reflect surface soil contamination level,
      land use, and soil runoff events. Using experimental results and theoretical
      modeling, the annual loading amount of dioxins at the middle reach of the river
      was estimated to be 0.458 mg WHO-TEQ in 2004. More than 96.6% of the annual
      loading amount was attributed to RR and derived almost evenly from forest and
      paddy fields at the study location. Because the annual loading amount at the
      middle reach is less than 0.5% of the total dioxins accumulated in the upper
      basin, dioxins runoff from the Japanese watershed will continue. This study shows
      that the combined use of the bioassay with HRGC/HRMS can provide new insights
      into dioxins transport and fate in the environment.

PMID- 19603633
TI  - Source tracking identifies deer and geese as vectors of human-infectious
      Cryptosporidium genotypes in an urban/suburban watershed.
AB  - This study identified Cryptosporidium genotypes in the Wissahickon watershed from
      May 2005 to April 2008. We analyzed 129 samples from Wissahickon Creek, 83
      effluent samples from wastewater treatment plants (WWTPs), and 240 fecal
      droppings. Genotyping was based on the hypervariable region of the 18S rRNA gene.
      Oocysts were detected year-round, independent of wet weather events, in 22% of
      Wissahickon Creek samples, 5% of WWTP effluents, and 7% of fecal samples. Of the
      genotypes detected, 67% were human-infectious: 30% C. hominis or C. hominis-like,
      12% C. parvum, 14% cervine genotype, 9% skunk genotype, and 1% chipmunk I
      genotype. Similar genotype profiles were detected in Wissahickon Creek each year,
      and human-infectious genotypes were detected year-round. Unusual genotypes
      detected in a deer (a C. hominis-like genotype) and geese (C. hominis-like
      genotypes, C. parvum, and muskrat genotype I) show that these animals are vectors
      of human-infectious genotypes in this watershed. Results suggest that deer,
      geese, and WWTPs are appropriate targets for source water protection in the
      Wissahickon watershed.

PMID- 19603634
TI  - Spatial heterogeneity of denitrification genes in a highly homogenous urban
      stream.
AB  - Human modification of natural streams by urbanization has led to more homogeneous
      channel surfaces; however, the influence of channel simplification on in situ
      microbial distribution and function is poorly characterized. For example,
      denitrification, a microbial process that reduces soluble nitrogen (N) levels,
      requires peripheral anoxic zones that might be lost in artificial channels such
      as those with a concrete lining. To examine how microbial function might be
      influenced by channel simplification, we quantified denitrification rates and
      conditions in microbial mats within an urban concrete channel. We quantified
      spatial and diurnal patterns of nitrate uptake, diurnal dissolved oxygen (DO)
      levels, and nutrient conditions, along with the spatial distribution of DO,
      solids, chlorophyll a, and genes associated with denitrification (nirS and nirK),
      ammonia-oxidizing bacteria (AOB), cyanobacteria, and algal chloroplasts. Despite
      the channel being superficially homogeneous, nir genes were distributed in a
      patchy manner. Two types of gene patches were observed: one associated with nirK,
      which had diurnally variable DO levels and high nocturnal nitrate uptake rates,
      and the other associated with nirS, which had elevated AOB genes, thicker layers
      of mud, and an apparent 24 h nitrate uptake. All active nir patches had elevated
      microbial photosynthetic genes. Results implythat even artificial channels, with
      reduced macroscale heterogeneity, can sustain significant rates of
      denitrification, although the responsible communities vary with space and time.
      This patchiness has significant implications to extending local data to landscape
      level predictions and field sampling strategies but also suggests alternate
      channel designs to increase N retention rates.

PMID- 19603635
TI  - Uranium phases in contaminated sediments below Hanford's U tank farm.
AB  - Macroscopic and spectroscopic investigations (XAFS, XRF, and TRLIF) on Hanford
      contaminated vadose zone sediments from the U-tank farm showed that U(VI) exists
      as different surface phases as a function of depth below ground surface (bgs).
      Secondary precipitates of U(VI) silicate precipitates (boltwoodite and
      uranophane) were present dominantly in shallow-depth sediments (15-16 m bgs),
      while adsorbed U(VI) phases and polynuclear U(VI) surface precipitates were
      considered to dominate in intermediate-depth sediments (20-25 m bgs). Only
      natural uranium was observed in the deeper sediments (> 28 m bgs) with no signs
      of contact with tank wastes containing Hanford-derived U(VI). Across all depths,
      most of the U(VI) was preferentially associated with the silt and clay size
      fractions of sediments. Strong correlation between U(VI) and Ca was found in the
      shallow-depth sediments, especially for the precipitated U(VI) silicates. Because
      U(VI) silicate precipitates dominate in the shallow-depth sediments, the released
      U(VI) concentration by macroscopic (bi)carbonate leaching resulted from both
      desorption and dissolution processes. Having different U(VI) surface phases in
      the Hanford contaminated sediments indicates that the U(VI) release mechanism
      could be complicated and that detailed characterization of the sediments using
      several different methods would be needed to estimate U(VI) fate and transport
      correctly in the vadose zone.

PMID- 19603636
TI  - Roadside, urban, and rural comparison of primary and secondary organic molecular
      markers in ambient PM2.5.
AB  - PM2.5 filter samples (12-h and 24-h) were collected in urban Atlanta, GA, next to
      a freeway and 400 m away, as well as at a rural site, with particular focus on
      exploring on-road emissions, regional transport, and biogenic effects. Detailed
      speciation of PM2.5 carbonaceous aerosols was conducted by GC/ MS. Diurnal,
      seasonal, and spatial variations of PM2.5 organic composition were investigated.
      Primary organic compounds usually exhibit different attributes of day vs night
      while secondary organic tracers varied little. Much higher concentrations of
      automotive-related primary organic compounds are observed at the highway site,
      including n-alkanes, hopanes, steranes, and polycyclic aromatic hydrocarbons
      (PAHs). Season-specific on-road mobile source primary OC profiles were developed
      by using differences in organic species concentrations between the highway site
      and the nearby site. Calculated on-road source profiles differ from mobile source
      profiles measured in the lab. Significant seasonal differences are observed for 2
      methyltetrols, cis-pinonic acid, and pinic acid, organic tracers of biogenic
      secondary organic aerosols (SOA). Little correlation is found between 2
      methyltetrols and cis-pinonic or pinic acid, though cis-pinonic and pinic acids
      are strongly correlated.

PMID- 19603637
TI  - American Healthy Homes Survey: a national study of residential pesticides
      measured from floor wipes.
AB  - The U.S. Department of Housing and Urban Development in collaboration with the
      United States Environmental Protection Agency conducted a survey measuring lead,
      allergens, and insecticides in a randomly selected nationally representative
      sample of residential homes. Multistage sampling with clustering was used to
      select the 1131 homes of which a subset of 500 randomly selected homes included
      the collection of hard surface floor wipes. Samples were collected by trained
      field technicians between June 2005 and March 2006 using isopropanol wetted
      wipes. Samples were analyzed for a suite of 24 compounds which included
      insecticides in the organochlorine, organophosphate, pyrethroid and
      phenylpyrazole classes, and the insecticide synergist piperonyl butoxide. The
      most commonly detected were permethrin (89%), chlorpyrifos (78%), chlordane
      (64%), piperonyl butoxide (52%), cypermethrin (46%), and fipronil (40%). Mean and
      geometric mean (GM) concentrations varied widely among compounds, but were
      highest for trans-permethrin (mean 2.22 ng/cm2 and GM 0.14 ng/ cm2) and
      cypermethrin (mean 2.9 ng/cm2 and GM 0.03 ng/ cm2). Results show that most floors
      in occupied homes in the U.S. have measurable levels of insecticides that may
      serve as sources of exposure to occupants.

PMID- 19603638
TI  - Assessment of in situ reductive dechlorination using compound-specific stable
      isotopes, functional gene PCR, and geochemical data.
AB  - Isotopic analysis and molecular-based bioassay methods were used in conjunction
      with geochemical data to assess intrinsic reductive dechlorination processes for
      a chlorinated solvent-contaminated site in Tucson, Arizona. Groundwater samples
      were obtained from monitoring wells within a contaminant plume comprising
      tetrachloroethene and its metabolites, trichloroethene, cis-1,2-dichloroethene,
      vinyl chloride, and ethene, as well as compounds associated with free phase
      diesel present at the site. Compound-specific isotope analysis was performed to
      characterize biotransformation processes influencing the transport and fate of
      the chlorinated contaminants. Polymerase chain reaction (PCR) analysis was used
      to assess the presence of indigenous reductive dechlorinators. The target regions
      employed were the 16s rRNA gene sequences of Dehalococcoides sp. and
      Desulfuromonas sp. and DNA sequences of genes pceA, tceA, bvcA, and vcrA, which
      encode reductive dehalogenases. The results of the analyses indicate that
      relevant microbial populations are present and that reductive dechlorination is
      presently occurring at the site. The results further show that potential degrader
      populations as well as biotransformation activity is nonuniformly distributed
      within the site. The results of laboratory microcosm studies conducted using
      groundwater collected from the field site confirmed the reductive dechlorination
      of tetrachloroethene to dichloroethene. This study illustrates the use of an
      integrated, multiple-method approach for assessing natural attenuation at a
      complex chlorinated solvent-contaminated site.

PMID- 19603639
TI  - Characterization of ragweed pollen adhesion to polyamides and polystyrene using
      atomic force microscopy.
AB  - Pollen is a leading contributor to asthma and allergies, yet pollen adhesion to
      common indoor surfaces is not well understood. We report the adhesive behavior of
      short ragweed (A. artemisiifolia) pollen grains with Nylon 6 (N6) and Nylon 6,6
      (N66), chosen due to their use in synthetic carpet, and three control surfaces:
      polyamide 12 (PA12), polystyrene (PS), and silicon. The forces were measured by
      using atomic force microscopy (AFM) under controlled humidity, where single
      pollen grains were attached to tipless AFM cantilevers. Pollen grains had an
      average adhesion of 10 +/- 3 nN with the surfaces, independent of surface type or
      relative humidity from 20% to 60%. van der Waals forces are the primary molecular
      attraction driving pollen adhesion to these surfaces. The results also indicate
      that ragweed pollen contacts the polymer surface via its exine surface spikes,
      and the total adhesion force scales with the number of contacts. The pollen
      surface spikes are strong, resisting fracture and compliance up to a load of 0.5
      GPa.

PMID- 19603640
TI  - Dietary exposure assessment of Chinese adults and nursing infants to
      tetrabromobisphenol-A and hexabromocyclododecanes: occurrence measurements in
      foods and human milk.
AB  - Tetrabromobisphenol A(TBBPA) and hexabromocyclododecane diastereoisomers (alpha,
      beta, and gamma-HBCD) were determined in 24 pooled human milk samples and 48
      Chinese total diet study (TDS) samples collected in 2007. On the basis of ultra
      performance liquid chromatography-mass spectrometry (UPLC-MS/MS) analysis, levels
      of TBBPA ranged from < LOD to 5124 pg/g lipid weight (lw) in human milk and from
      < LOD to 2044 pg/g lw in TDS samples. The alpha-HBCD diastereoisomer, which
      ranged from < LOD to 2776 pg/g lw in human milk and from < LOD to 2224 pg/g lw in
      TDS samples, was generally the most abundant isomer comparing with beta- and
      gamma-HBCD. The average estimated daily intake (EDI) of TBBPA via human milk for
      nursing infants with a range 320-37240 pg/kg bodyweight (bw)/day was 5094 pg/kg
      bw/day, while that of sigmaHBCD was 5837 pg/kg bw/day with a range 670-17320
      pg/kg bw/day. The medium bound (< LOD = 1/2LOD) EDI(TBBPA) for a "reference" man
      via animal origin foods was 256 pg/kg bw/day and EDI(sigmaHBCD) was 432 pg/kg
      bw/day. Meat and meat products were the main source in the total dietary intake
      of TBBPA and sigmaHBCD. Our research on the estimated daily intake of TBBPA and
      sigmaHBCD by the Chinese population indicated large variations in TBBPA and
      sigmaHBCD levels between provinces. Overall, our data indicate the Chinese EDI
      was lowerthan the EDI from similar studies in Europe.

PMID- 19603641
TI  - Increased dissolved organic carbon (DOC) in Central European streams is driven by
      reductions in ionic strength rather than climate change or decreasing acidity.
AB  - Temporal trends in DOC concentration and flux were investigated at two
      geochemically distinct forested catchments in western Czech Republic. Mean
      discharge-weighted DOC concentrations averaged 18.8 mg L(-1) at the acidic Lysina
      catchment, and 20.2 mg L(-1) at base-rich and well-buffered Pluhuv Bor. Between
      1993 and 2007 DOC in streamwater increased significantly in both catchments: the
      mean annual increase was 0.42 mg L(-1) yr(-1) (p < 0.001) at Lysina and 0.43 mg
      L(-1) yr(-1) (p < 0.001) at Pluhuv Bor, resulting in cumulative increases of 64
      and 65%, respectively. These long-term increases in streamwater DOC were
      correlated with only modest increases in stream pH in both catchments, but large
      declines in ionic strength (IS), that resulted from declining atmospheric
      deposition. Neither catchment has undergone changes in soil-water pH, yet DOC
      concentrations tripled in the soil-water of both catchments. We conclude that
      changes in ionic strength of soil-water and streamwater, rather than acidity, are
      the primary drivers of changes in streamwater DOC in this region. Temperature,
      precipitation and discharge show no statistically significant trends during the
      study period, suggesting that climate change has played no role in the changes in
      DOC that we have observed.

PMID- 19603642
TI  - Stable isotopes as a tool to apportion atmospheric iron.
AB  - Identification of atmospheric iron is a key parameter to understanding the source
      of iron in urban and remote areas. Atmospheric deposition of desert dust, which
      also can include an anthropogenic component, is a primary nutrient source for
      most of the open ocean. To better assess particulate matter (PM) sources specific
      to iron, we measured the iron isotopic composition of aerosols in two size
      fractions: PM with aerodynamic diameters less than 2.5 microm and less than 10
      microm (PM2.5 and PM10, respectively). Using colocated samplers, atmospheric
      aerosol samples were collected in the U.S. desert Southwest at a mixed
      suburban/agricultural site near Phoenix, AZ. The measurements are presented as
      delta56Fe relative to the IRMM-014 (Institute for Reference Materials and
      Measurements) standard. Using multiple collector inductively coupled plasma mass
      spectrometry, we found differences in iron isotopic composition within the PM10
      aerosol. Half of the PM10 samples had an iron isotopic signature similar to
      crustal material (+0.03 per thousand), which implicates wind-blown soil-dust as
      the primary source. The other PM10 samples showed a lighter iron isotopic
      composition, centered at -0.18 per thousand. Further analysis showed thatthe
      lighter iron was associated with winds originating from the southwest. This
      strongly suggests that there is a different PM10 source in this direction, with a
      distinct iron isotopic composition. The iron in the PM2.5 samples was usually
      substantially lighter than the corresponding PM10 samples, which is consistent
      with coarse and fine particles having different sources, again with distinctively
      different isotopic compositions. The magnitude of the iron isotopic difference
      between the PM10 and the PM2.5 size fractions (delta56Fe(PM10) -
      delta56Fe(PM2.5)) correlated with the PM2.5 concentrations of elements known to
      be emitted from industrial sources (Pb, Cd, As, V, and Cr). This observation
      implies that the isotopically light iron is created or emitted alongside
      industrial processes. Our data demonstrate that iron isotope composition can be a
      valuable tool in the source-apportionment of iron in atmospheric particles.

PMID- 19603643
TI  - Sea ice-associated diet change increases the levels of chlorinated and brominated
      contaminants in polar bears.
AB  - Two global environmental issues, climate change and contamination by persistent
      organic pollutants, represent major concerns for arctic ecosystems. Yet, it is
      unclear how these two stressors interact in the Arctic. For instance, the
      influence of climate-associated changes in food web structure on exposure to
      pollutants within arctic ecosystems is presently unknown. Here, we report on
      recent changes in feeding ecology (1991-2007) in polar bears (Ursus maritimus)
      from the western Hudson Bay subpopulation that have resulted in increases in the
      tissue concentrations of several chlorinated and brominated contaminants.
      Differences in timing of the annual sea ice breakup explained a significant
      proportion of the diet variation among years. As expected from climate change
      predictions, this diet change was consistent with an increase in the consumed
      proportions of open water-associated seal species compared to ice-associated seal
      species in years of earlier sea ice breakup. Our results demonstrate that climate
      change is a modulating influence on contaminants in this polar bear subpopulation
      and may pose an additional and previously unidentified threat to northern
      ecosystems through altered exposures to contaminants.

PMID- 19603644
TI  - Escherichia coil O157:H7 transport in saturated porous media: role of solution
      chemistry and surface macromolecules.
AB  - The transport and deposition behavior of Escherichia coli O157: H7 was
      investigated in saturated packed-bed columns and micromodel systems over a range
      of ionic strength (IS) (1, 10, and 100 mM) and pH (5.8, 8.4, and 9.2) conditions.
      At a given IS, elevated solution pH resulted in decreased deposition as a result
      of the increase in the measured zeta potential of the quartz sand. This
      deposition trend was consistent with predictions from classic Derjaguin-Landau
      Verwey-Overbeek (DLVO) theory. Conversely, the E. coil O157:H7 deposition was
      inversely proportionalto IS (1-100 mM) at high pH conditions (8.4 and 9.2),
      whereas no effect of IS was observed at pH 5.8. This deposition trend was not
      consistent with DLVO theory, but could be explained by pH-associated
      electrosteric stabilization. This phenomenon is driven by the pH-dependent
      protonated state of functional groups on E. coil O157:H7 surface macromolecules
      and the corresponding conformational state of the bacterial polymers. Results
      from this study demonstrate that retention of E. coil O157:H7 cells in porous
      media is a complex process that depends on the solution chemistry, cell-cell
      interactions, and pore structure. The findings in this study also imply that
      previous work conducted at lower pH and IS conditions may underestimate E. coli
      O157:H7 travel distance in higher salt and pH groundwater environments.

PMID- 19603645
TI  - Relationship between photosensitizing and emission properties of peat humic acid
      fractions obtained by tangential ultrafiltration.
AB  - Peat humic acid was fractionated by tangential ultrafiltration into six nominal
      molecular weight (NMW) fractions, HA5-10, HA10-20, HA20-50, HA50-100, HA100-300
      and HA > 300, which were purified by dialysis using a 0.5 kDa membrane. The
      absorbing and emission properties of the separated fractions were compared and
      their ability to generate singlet oxygen under light excitation was evaluated,
      using furfuryl alcohol (FFA) as a singlet oxygen scavenger. The absorbance, the
      emission intensity, and the apparent first order rate constants of FFA loss were
      normalized per mole of organic carbon (a*, IF*, and k*, respectively). The
      fraction absorbance decreased with NMW, except for HA > 300 which was less
      absorbing than HA100-300. The low NMW fractions and the HA > 300 fraction
      generally showed lower k* and IF* values compared to the HA50-100 and HA100-300
      fractions. A plot of k* versus IF* indicates that the first order rate constant
      of FFA photo-oxygenation increased with the intensity of fluorescence at 380,
      430, and 500 nm (R2 = 0.77-0.84). This shows that the distribution of fluorescent
      centers among fractions paralleled that of photosensitizing centers. Plotting k*
      or IF* versus a* at365 nm reveals the apparent relative quantum efficiency of the
      different fractions. Higher values for low NMW fractions and HA50-100 are either
      due higher percentages of absorbing centers able to produce singlet oxygen or
      exhibit fluorescence or to lower quenching processes.

PMID- 19603646
TI  - Comparative photoactivity and antibacterial properties of C60 fullerenes and
      titanium dioxide nanoparticles.
AB  - The production of reactive oxygen species (ROS) by aqueous suspensions of
      fullerenes and nano-TiO2 (Degussa P25) was measured both in ultrapure water and
      in minimal Davis (MD) microbial growth medium. Fullerol (hydroxylated C60)
      produced singlet oxygen (1O2) in ultrapure water and both 1O2 and superoxide (O2
      *) in MD medium, but no hydroxyl radicals (OH*) were detected in either case.
      PVP/C60 (C60 encapsulated with poly(N-vinylpyrrolidone)) was more efficient than
      fullerol in generating singlet oxygen and superoxide. However, two other
      aggregates of C60, namely THF/nC60 (prepared with tetrahydofuran as transitional
      solvent) and aqu/nC60 (prepared by vigorous stirring of C60 powder in water),
      were not photoactive. Nano-TiO2 (also present as aggregates) primarily produced
      hydroxyl radicals in pure water and superoxide in MD medium. Bacterial
      (Escherichia coli) toxicity tests suggest that, unlike nano-TiO2 which was
      exclusively phototoxic, the antibacterial activity of fullerene suspensions was
      linked to ROS production. Nano-TiO2 may be more efficient for water treatment
      involving UV or solar energy, to enhance contaminant oxidation and perhaps for
      disinfection. However, fullerol and PVP/ C60 may be useful as water treatment
      agents targeting specific pollutants or microorganisms that are more sensitive to
      either superoxide or singlet oxygen.

PMID- 19603647
TI  - Spatial variability in mercury cycling and relevant biogeochemical controls in
      the Florida Everglades.
AB  - Spatial patterns in mercury cycling and bioaccumulation at the landscape level in
      the Everglades were investigated by collecting and analyzing multimedia samples
      for mercury species and biogeochemical characteristics from 228 randomly located
      stations. Higher total mercury (THg) in environmental compartments (surface
      water, soil, flocculent detrital material (floc), and periphyton) generally
      occurred in the northern and central Everglades, but higher THg in water and
      periphyton in the Everglades National Park was an exception. Multiple
      biogeochemical characteristics, such as surface water dissolved organic matter
      (DOC(sw)), pH, chloride, and compositional properties of solid compartments (soil
      and floc), were identified to be important factors controlling THg distribution.
      Methylmercury (MeHg) was also higher in the northern Everglades for water, soil,
      and floc, but not for periphyton. Higher mosquitofish THg and bioaccumulation
      factor were observed in the central and southern Everglades, partially in
      accordance with periphyton MeHg distribution, but not in the "hot spot" areas of
      water, soil, or floc MeHg. The discrepancy in mercury bioaccumulation and mercury
      distribution in environmental compartments suggests that in addition to MeHg
      production, biogeochemical controls that make MeHg available to aquatic
      organisms, such as DOC(sw) and compositional properties of soil and floc, are
      important in mercury bioaccumulation.

PMID- 19603648
TI  - Effects of sol-gel synthesis on 5Fe-15Mn-40Zn-40Ti-O mixed oxide structure and
      its H2S removal efficiency from industrial gas streams.
AB  - A novel Fe-Mn-Zn-Ti-O mixed metal oxide has been developed for efficient low
      temperature (25-50 degrees C) removal of H2S from a gas mixture containing 600
      ppm H2S, 25 vol% H2, 7.5 vol % CO2, and 1-3 vol% H2O that simulates typical
      conditions experienced at the outlet of a bioreactor loaded with sulfate metal
      reducing bacteria (SMRB) that converts toxic Cr6+ and As5+ present in ground and
      surface waters and soils into nontoxic elements. During the latter conversion H2S
      gas is produced and has to be treated. In the present work it is demonstrated for
      the first time that by using the sol-gel synthesis route at given experimental
      conditions (e.g., metal precursor salts, solvent system, and solution pH),
      optimum structural properties for the Fe-Mn-Zn-Ti-O solid can be obtained for
      maximization of H2S uptake. In particular, at 25 degrees C an H2S uptake (0.085 g
      H2S/g solid) larger by at least a factor of 3 compared to a commercial Ni-based
      H2S absorbent material was obtained.

PMID- 19603649
TI  - Enhancement of waste activated sludge protein conversion and volatile fatty acids
      accumulation during waste activated sludge anaerobic fermentation by carbohydrate
      substrate addition: the effect of pH.
AB  - Volatile fatty acids (VFAs), the carbon source of biological nutrients removal,
      can be produced by waste activated sludge (WAS) anaerobic fermentation. However,
      because of high protein content and low carbon to nitrogen mass ratio (C/N) of
      WAS, the production of VFAs, especially propionic acid, a more preferred VFA than
      acetic acid for enhanced biological phosphorus removal (EBPR), is limited. After
      the addition of carbohydrate (rice was used as the model matter) to the WAS
      anaerobic fermentation system to balance the C/N ratio, the effect of pH on WAS
      protein conversion and VFAs production was investigated in this paper.
      Experimental results showed that the addition of carbohydrate matter caused a
      remarkable enhancement of WAS protein conversion and protease activity, and an
      apparent synergistic effect between WAS and carbohydrate matter was observed. The
      study of pH effect revealed that pH influenced not only the total VFAs production
      but the percentage of individual VFA. The maximal VFAs production (520.1 mg COD
      per gram of volatile suspended solids (VSS)) occurred at pH 8.0 and a
      fermentation time of 8 d, which was more than three times that at uncontrolled pH
      (150.2 mg COD/g VSS). The analysis of the composition of VFAs showed that
      propionic acid ranked first at pH 6.0-9.0 (around 50%) whereas acetic acid was
      the dominant product at other pHs investigated. Thus, the suitable conditions for
      propionic acid-enriched VFAs production were pH 8.0 and a time of 8 d. Further
      investigation showed that as there was more fermentation substrate consumption
      with lower biogas generation at pH 8.0, improved VFAs production was observed.
      Also, the key enzymes relevant to propionic acid formation exhibited the highest
      activities at pH 8.0, which resulted in the greatest propionic acid content in
      the fermentative VFAs. The 16S rRNA gene clone library demonstrated that
      Clostridia, beta-Proteobacteria, and Bacteroidetes were the dominant microbial
      community when the current anaerobic fermentation system was operated at pH 8.0.
      With the fermentative VFAs as the additional carbon source of municipal
      wastewater, the EBPR performance was significantly increased.

PMID- 19603650
TI  - Ubiquitous occurrence of the artificial sweetener acesulfame in the aquatic
      environment: an ideal chemical marker of domestic wastewater in groundwater.
AB  - Artificial low-calorie sweeteners are consumed in considerable quantities with
      food and beverages. After ingestion, some sweeteners pass through the human
      metabolism largely unaffected, are quantitatively excreted via urine and feces,
      and thus reach the environment associated with domestic wastewater. Here, we
      document the widespread occurrence of four sweeteners in the aquatic environment
      and show that one of these compounds, acesulfame, meets all of the criteria of an
      ideal marker for the detection of domestic wastewater in natural waters,
      particularly groundwater. Acesulfame was consistently detected in untreated and
      treated wastewater (12-46 microg/L), in most surface waters, in 65% of the
      investigated groundwater samples, and even in several tap water samples (up to
      2.6 microg/L) from Switzerland. The sweetener was not eliminated in wastewater
      treatment plants (WWTPs) and was quite persistent in surface waters, where
      concentrations increased with population in the catchment area and decreased with
      water throughflow. The highest concentrations in groundwater, up to 4.7 microg/L,
      were observed in areas with significant infiltration of river water, where the
      infiltrating water received considerable discharges from WWTPs. Given the
      currently achieved detection limit of approximately 0.01 microg/L, it is possible
      to trace the presence of > or = 0.05% wastewater in groundwater.

PMID- 19603651
TI  - Influence of heterogeneous ammonium availability on bacterial community structure
      and the expression of nitrogen fixation and ammonium transporter genes during in
      situ bioremediation of uranium-contaminated groundwater.
AB  - The influence of ammonium availability on bacterial community structure and the
      physiological status of Geobacter species during in situ bioremediation of
      uranium-contaminated groundwater was evaluated. Ammonium concentrations varied by
      2 orders of magnitude (< 4 to 400 microM) across th study site. Analysis of 16S
      rRNA sequences suggested that ammonium may have been one factor influencing the
      community composition prior to acetate amendment with Rhodoferax species
      predominating over Geobacter species with higher ammonium and Dechloromonas
      species dominating at the site with lowest ammonium. However, once acetate was
      added and dissimilatory metal reduction was stimulated, Geobacter species became
      the predominant organisms at all locations. Rates of U(VI) reduction appeared to
      be more related to acetate concentrations rather than ammonium levels. In situ
      mRNA transcript abundance of the nitrogen fixation gene, nifD, and the ammonium
      transporter gene, amtB, in Geobacter species indicated that ammonium was the
      primary source of nitrogen during uranium reduction. The abundance of amtB was
      inversely correlated to ammonium levels, whereas nifD transcript levels were
      similar across all sites examined. These results suggest that nifD and amtB
      expression are closely regulated in response to ammonium availability to ensure
      an adequate supply of nitrogen while conserving cell resources. Thus, quantifying
      nifD and amtB transcript expression appears to be a useful approach for
      monitoring the nitrogen-related physiological status of subsurface Geobacter
      species. This study also emphasizes the need for more detailed analysis of
      geochemical and physiological interactions at the field scale in order to
      adequately model subsurface microbial processes during bioremediation.

PMID- 19603652
TI  - Role of extracellular polymeric substances (EPS) in biofouling of reverse osmosis
      membranes.
AB  - This study elucidates the mechanisms by which extracellular polymeric substances
      (EPS) impact permeate water flux and salt rejection during biofouling of reverse
      osmosis (RO) membranes. RO fouling experiments were conducted with Pseudomonas
      aeruginosa PAO1, EPS extracted from PAO1 biofilms, and dead PAO1 cells fixed in
      formaldehyde. While a biofouling layer of dead bacterial cells decreases salt
      rejection and permeate flux by a biofilm-enhanced osmotic pressure mechanism, the
      EPS biofouling layer adversely impacts permeate flux by increasing the hydraulic
      resistance to permeate flow. During controlled fouling experiments with extracted
      EPS in a simulated wastewater solution, polysaccharides adsorbed on the RO
      membranes much more effectively than proteins (adsorption efficiencies of 61.2
      88.7% and 11.6-12.4% for polysaccharides and proteins, respectively). Controlled
      fouling experiments with EPS in sodium chloride solutions supplemented with 0.5
      mM calcium ions (total ionic strength of 15 mM) indicate that calcium increases
      the adsorption efficiency of polysaccharides and DNA by 2- and 3-fold,
      respectively. The increased adsorption of EPS onto the membrane resulted in a
      significant decrease in permeate water flux. Corroborating with these calcium
      effects, atomic force microscopy (AFM) measurements demonstrated that addition of
      calcium ions to the feed solution results in a marked increase in the adhesion
      forces between a carboxylated particle probe and the EPS layer. The increase in
      the interfacial adhesion forces is attributed to specific EPS-calcium
      interactions that play a major role in biofouling of RO membranes.

PMID- 19603653
TI  - Isotopic fractionation of Sn during methylation and demethylation reactions in
      aqueous solution.
AB  - Laboratory experiments, modeling the methylation of inorganic Sn(II) by
      methylcobalamin and the decomposition of methyltin under irradiation with UV
      light in aqueous solution, have been performed. Methyltin has been separated from
      inorganic Sn using anion-exchange chromatography and subjected to Sn isotope
      ratio measurements via solution nebulization multicollector inductively coupled
      plasma mass spectrometry (MC-ICPMS). The methylation of Sn(II) in the dark was
      accompanied by mass-dependent Sn isotopic fractionation, which resulted in
      preferential partitioning of the lighter Sn isotopes into the organic phase, with
      a shift of approximately 0.57 +/- 0.12 per thousand in terms of delta124/ 116Sn
      between methylated and inorganic Sn. The methylation of Sn(II) by methylcobalamin
      under UV irradiation resulted in the accelerated formation of methyltin in the
      beginning of the process, but was followed by the photolytic degradation of
      methyltin until its complete mineralization. The photolytic degradation of
      methyltin in the presence of methylcobalamin and inorganic Sn(II) was slower than
      that of pure solutions of commercially obtained monomethyltin. This is attributed
      to the methylating action of methyl radicals produced from photolytically
      decomposing methylcobalamin. Both synthesis and decomposition of methyltin under
      UV irradiation were accompanied by both mass-dependent and mass-independent Sn
      isotopic fractionation, with the latter due to the magnetic isotope effect. As a
      result of this, the lighter Sn isotopes preferentially partition into reaction
      products, while the odd isotopes, 117Sn and 119Sn, are selectively enriched
      relative to the other isotopes in the starting molecules. The extent of the
      observed variations in the isotopic composition of Sn is larger than that
      documented previouslyfor geological and archeological samples. These results
      indicate that Sn isotopic fractionation between various chemical forms of Sn in
      the natural aquatic systems may be significant and can provide new insights into
      the biogeochemical cycling of the element.

PMID- 19603654
TI  - Photochemical formation of halogenated dioxins from hydroxylated polybrominated
      diphenyl ethers (OH-PBDEs) and chlorinated derivatives (OH-PBCDEs).
AB  - The potential photochemical formation of polybrominated and mixed halogenated
      dibenzo-p-dioxins (PBDDs and PXDDs) from hydroxylated polybrominated and
      polybrominated/ chlorinated diphenyl ethers (OH-PBDEs and OH-PBCDEs) in aqueous
      solution was studied. The ortho-hydroxylated BDE47 derivative 6-OH-BDE47, and
      chlorinated derivatives 3-Cl-6-OH-BDE47, 5-Cl-6-OH-BDE47, and 3,5-Cl-6-OH-BDE47
      were photolyzed under sunlight at 45 degrees N latitude in buffered waters,
      Mississippi River water, Lake Josephine water, and ultrapure water adjusted to
      the pH of the natural waters. Chemical actinometry was used to determine reactant
      quantum yields which were calculated to be between 0.03 and 0.21, with lower
      yields for the chlorinated derivatives under all conditions. Quantum yields under
      natural water conditions were not significantly enhanced indicating that direct
      photolysis is the primary process of photochemical degradation. The formation of
      halogenated dioxins from the outdoor photolysis of the four OH-PBDEs/OH-PBCDEs
      under all conditions was confirmed. Dioxin yields of 0.7-3.6% were found, with
      higher yields for 6-OH-BDE47 under all conditions. This study suggests that
      photolysis of OH-PBDEs and OH-PBCDEs is a potential formation pathway of PBDDs
      and PXDDs in the environment.

PMID- 19603655
TI  - Identification and distribution of vanadinite (Pb5(V5+O4)3Cl) in lead pipe
      corrosion by-products.
AB  - This study presents the first detailed look at vanadium (V) speciation in
      drinking water pipe corrosion scales. A pool of 34 scale layers from 15 lead or
      lead-lined pipes representing eight different municipal drinking water
      distribution systems in the Northeastern and Midwestern portions of the United
      States were examined. Diverse synchrotron-based techniques, including bulk XANES
      (X-ray absorption near edge spectroscopy), micro-XANES, micro-XRD (X-ray
      diffraction), and micro-XRF (X-ray fluorescence) mapping were employed along with
      traditional powder XRD, SEM-EDXA (scanning electron microscopy-energy dispersive
      X-ray analysis), and ICP-OES (inductively coupled plasma-optical emission
      spectrometry) to evaluate vanadium speciation and distribution in these deposits.
      Vanadinite (Pb5(VO4)3Cl) was positively identified, and occurred most frequently
      in the surface layers. Low V(tot) in these waters is likely the limiting factor
      in the abundance of vanadinite in the pipe scales, along with the existence of
      divalent lead. The occurrence of V in these samples as a discrete mineral is
      important because it is formed in the presence of very low concentrations of V in
      the finished water, it provides a mechanism to concentrate microg x L(-1) amounts
      of V from the water to near-percent levels in the pipe scales, and the robustness
      of V accumulation and release in response to water chemistry changes is likely
      different than it would be with a sorption accumulation mechanism. Extrapolation
      from limited existing water chemistry data in this study provides an estimate of
      deltaG(f)degrees for vanadinite as approximately -3443 kJ x mol(-1), or less,
      leading to a log K(s)0 value of approximately -86 for the reaction Pb5(VO4)3CI(s)
      equilibrium {Pb2+}5 + {VO4(3-) + {Cl-}, in which {} denotes activity.

PMID- 19603656
TI  - A correlation for the collector efficiency of Brownian particles in clean-bed
      filtration in sphere packings by a Lattice-Boltzmann method.
AB  - In this paper, we develop a new correlation for the clean-bed filter coefficient
      (lambda0) for Brownian particles, for which diffusion is the main deposition
      mechanism. The correlation is based on numerical Lattice-Boltzmann (LB)
      simulations in random packings of spheres of uniform diameter. We use LB methods
      to solve the Navier-Stokes equation for flow and then the advection-diffusion
      equation for particle transport. We determine a correlation for an "equivalent"
      single-collector diffusion efficiency, etaD, so that we can compare our
      predictions to "true" single-collector correlations stemming from unit-cell
      modeling approaches. We compared our new correlation to experiments on the
      filtration of latex particles. For small particle diameters, 50 nm < dp < 300 nm,
      when gravity and interception are negligible, our correlation for etaD predicts
      measurements better than unit-cell correlations, which overestimate etaD. The
      good agreement suggests that the representation of three-dimensional transport
      pathways in porous media plays an important role when modeling transport and
      deposition of Brownian particles. To model larger particles, for which gravity
      and interception are important too, we build a correlation for the overall single
      collector efficiency eta0 by adding corresponding etaG and nI terms from unit
      cell correlations to our etaD model. The resulting correlation predicts
      experiments with latex particles of dp > 300 nm well.

PMID- 19603657
TI  - Ionic strength dependent transport of microparticles in saturated porous media:
      modeling mobilization and immobilization phenomena under transient chemical
      conditions.
AB  - This study investigates ionic strength dependent deposition and release of
      microparticles in saturated porous media. Controlled micrometer-sized particle
      deposition experiments were conducted, followed by stepwise modifications in
      porewater chemistry to induce retained particle mobilization. A transient dual
      site transport model was tested against deposition and release, systematically
      addressing the effect of variations in solution ionic strength by coupling the
      equations for colloid transport with that for solute transport. The attachment
      and detachment coefficients of the model equations were explicitly tied to the
      salt concentration through proposed empirical functions, derived from
      experimental and theoretical considerations. Two regimes of attachment (and
      detachment) were hypothesized, showing favorable behavior beyond modeled values
      of a critical deposition concentration (and critical release concentration).
      Blocking phenomena were accounted for as well. This work shows how the intimate
      inclusion of salt concentration in a unique model equation system is able to
      describe both deposition and release behaviors of the particles under transient
      chemical conditions.

PMID- 19603659
TI  - PARAFAC modeling of fluorescence excitation-emission spectra of fish bile for
      rapid en route screening of PAC exposure.
AB  - Polycyclic aromatic compound (PAC) metabolites in fish bile can be used as
      biomarkers for recent environmental exposure to PACs. Here, a novel method for
      rapid screening of nonhydrolyzed fish bile is presented. The method is based on
      excitation-emission fluorescence spectroscopy combined with parallel factor
      analysis (PARAFAC) and may constitute an alternative to fixed wavelength
      fluorescence and synchronous fluorescence spectroscopy (SFS). PARAFAC was applied
      to excitation-emission matrices (EEMs) of bile samples of shorthorn sculpins and
      European eels collected in Greenland and Denmark. The EEMs were decomposed into a
      four-factor PARAFAC model. The comparison of the PARAFAC factors with the EEMs of
      PAC metabolites and amino acids suggests that two factors are related to PAC
      metabolites and two correspond to fluorescent residues of tryptophan and tyrosine
      in bile proteins. A new standardization procedure based on the mean of the scores
      for the biological factors was used to correct for feeding status and sample
      dilution and, upon such normalization, the score plots of PARAFAC factors showed
      a clear distinction between exposed and nonexposed fish. A good correlation was
      found between the factor scores and 1-hydroxypyrene equivalents determined by SFS
      for high contamination levels, whereas the sensitivity was better for the EEM
      method.

PMID- 19603660
TI  - Enhanced uranium sorption on aluminum oxide pretreated with arsenate. Part I:
      Batch uptake behavior.
AB  - We explored mechanisms for increasing U(VI) sorption by pretreating alumina
      surfaces with arsenate, which has a high affinity for binding with uranyl and is
      an analog for phosphate. Batch experiments were conducted at pH approximately 4
      by pretreating a gamma-alumina surface with arsenate, followed by the addition of
      uranyl. Parallel experiments were conducted with different alumina loadings as
      well as As and U concentrations. Results show positive correlations between U(VI)
      uptake and [As]ini/[U]ini (ratio between the initial As solution concentration
      for pretreatment and the initial U solution concentration), suggesting the
      formation of ternary surface complexes and/or precipitates. Desorption
      experiments show partial irreversibility of the adsorbed U, suggesting less
      likelihood of remobilization. The pretreatment process results in enhanced U
      uptake and enhanced stability of the sorbed U, and provides a basis for designing
      other treatment processes for selective remediation applications.

PMID- 19603658
TI  - Validation of Bayesian kriging of arsenic, chromium, lead, and mercury surface
      soil concentrations based on internode sampling.
AB  - Bayesian kriging is a useful tool for estimating spatial distributions of metals;
      however, estimates are generally only verified statistically. In this study
      surface soil samples were collected on a uniform grid and analyzed for As, Cr,
      Pb, and Hg. The data were interpolated at individual locations by Bayesian
      kriging. Estimates were validated using a leave-one-out cross validation (LOOCV)
      statistical method which compared the measured and LOOCV predicted values.
      Validation also was carried out using additional field sampling of soil metal
      concentrations at points between original sampling locations, which were compared
      to kriging prediction distributions. LOOCV results suggest that Bayesian kriging
      was a good predictor of metal concentrations. When measured internode metal
      concentrations and estimated kriged values were compared, the measured values
      were located within the 5th-95th percentile prediction distributions in over half
      of the internode locations. Estimated and measured internode concentrations were
      most similar for As and Pb. Kriged estimates did not compare as well to measured
      values for concentrations below the analytical minimum detection limit, or for
      internode samples that were very close to the original sampling node. Despite
      inherent variability in, metal concentrations in soils, the kriged estimates were
      validated statistically and by in situ measurement.

PMID- 19603661
TI  - Enhanced uranium sorption on aluminum oxide pretreated with arsenate. Part II:
      Spectroscopic studies.
AB  - In a companion study, we demonstrated that pretreatment of gamma-alumina surface
      with arsenate enhances uranyl uptake under acidic conditions, where uranyl
      otherwise sorbs poorly. Here, we examine the local structure and long-range order
      of the sorption products by using X-ray absorption spectroscopy (XAS) and X-ray
      diffraction (XRD). Arsenate was chosen for the pretreatment because of its high
      affinity for binding with uranyl and alumina, and because it is an analog for
      environmentally abundant and commercially accessible phosphate. It also
      facilitates characterization of sorption products using As K-edge XAS, which
      complements U LIII-edge XAS. Fitting results suggest the formation of U-As
      precipitates with structures similar to UO2HAsO4 x 4H2O (trogerite) and likely U
      polymeric species at high U concentrations. The ratios among surface-sorbed
      uranyl, U-As precipitates, and uranyl polymeric species are dependent on the
      [As]initial/[U]initial ratio and absolute initial U concentration. XRD suggests
      the precipitates are likely to be highly disordered and poorly crystalline.
      Current findings evaluate the mechanism by which the pretreatment results in
      enhanced U uptake and stability and provides a conceptual basis for designing
      other pretreatment technologies for uranium remediation.

PMID- 19603662
TI  - Reducing PAH emissions from the iron ore sintering process by optimizing its
      operation parameters.
AB  - This study set out to reduce polycyclic aromatic hydrocarbon (PAH) emissions from
      the iron ore sintering process by optimizing its operation parameters obtained
      from the Taguchi experimental design. Four operating parameters, including the
      water content (Wc; range = 6.0-7.0 wt %), suction pressure (Ps; range = 1000-1400
      mmH2O), bed height (Hb; range = 500-600 mm), and type of hearth layer (HL;
      including sinter, hematite, and limonite) were selected and conducted on a pilot
      scale sinter pot to simulate various sintering operating conditions of a real
      scale sinter plant. We found that the resultant optimal combination (Wc = 6.5 wt
      %, Hb = 600 mm, Ps = 1400 mmH2O, and HL = limonite) could reduce the emission
      factor of total BaP equivalent concentration (EF(BaPeq)) up to 57.6% in
      comparison with the current operating condition of a real-scale sinter plant (Wc
      = 6.5 wt %, Hb = 550 mm, Ps = 1200 mmH2O, and HL = sinter). Through the ANOVA
      analysis, we found that Ps and Hb were the top two parameters affecting total
      EF(BaPeq) (accounting, respectively, for 70.9% and 21.2% of the total
      contribution of the four selected parameters). By examining both the sinter
      productivity and sinter strength, the values obtained from the optimal
      combination were quite comparable to those of the current operating condition.
      The above results further confirm the applicability of the obtained optimal
      combination for the real-scale sinter plant.

PMID- 19603663
TI  - Biological perchlorate reduction in packed bed reactors using elemental sulfur.
AB  - Sulfur-utilizing perchlorate (ClO4-)-reducing bacteria were enriched from a
      denitrifying wastewater seed with elemental sulfur (S0) as an electron donor. The
      enrichment was composed of a diverse microbial community, with the majority
      identified as members of the phylum Proteobacteria. Cultures were inoculated into
      bench-scale packed bed reactors (PBR) with S0 and crushed oyster shell packing
      media. High ClO4-concentrations (5-8 mg/L) were reduced to < 0.5 mg/L at an empty
      bed contact time (EBCT) of 13 h. Low C1O4- concentrations (60-120 microg/L), more
      typical of contaminated groundwater sites, were reduced to < 4 microg/L at an
      EBCT of 7.5 h. PBR performance decreased when effluent recirculation was applied
      or when smaller S0 particle sizes were used, indicating that mass transfer of
      ClO4- to the attached biofilm was not the limiting mechanism in this process, and
      that biofilm acclimation and growth were key factors in overall reactor
      performance. The presence of nitrate (6.5 mg N/L) inhibited ClO4- reduction. The
      microbial community composition was found to change with ClO4- availability from
      a majority of Beta-Proteobacteria near the influent end of the reactor to
      primarily sulfur-oxidizing bacteria near the effluent end of the reactor.

PMID- 19603664
TI  - Three year field test of a plant growth promoting rhizobacteria enhanced
      phytoremediation system at a land farm for treatment of hydrocarbon waste.
AB  - Phytoremediation of total petroleum hydrocarbons (TPH) has the potential to be a
      sustainable waste management technology if it can be proven to be effective in
      the field. Over the past decade, our laboratory has developed a system which
      utilizes plant growth promoting rhizobacteria (PGPR) enhanced phytoremediation
      (PEP) that, following extensive greenhouse testing, was shown to be effective at
      remediating TPH from soils. This system consists of physical soil manipulation
      and plant growth following seed inoculation with PGPR. PGPR elicit biomass
      increases, particularly in roots, by minimizing plant stress in highly
      contaminated soils. Extensive development of the root system enhances degradation
      of contaminants by the plants and supports an active rhizosphere that effectively
      promotes TPH degradation by a broad microbial consortium. Following promising
      greenhouse trials, field tests of PEP were performed over a period of three years
      at a Southern Ontario site (approximately 130 g kg(-1) TPH) used for land farming
      of refinery hydrocarbon waste for many years. The low molecular weight fractions
      (the Canadian Council of Ministers of the Environment (CCME) fractions 1 and 2)
      were removed through land farming and bioremediation; the high molecular weight,
      recalcitrant fractions (CCME fractions 3 and 4) remained at high levels in the
      soil. Using PEP, we substantially remediated fractions 3 and 4, and lowered TPH
      from 130 g kg(-1) to approximately 50 g kg(-1) over a three year period. The
      amount of plant growth and extent of oil remediation were consistently enhanced
      by PGPR.

PMID- 19603665
TI  - Reaction of tetrabromobisphenol A (TBBPA) with manganese dioxide: kinetics,
      products, and pathways.
AB  - Birnessite (delta-MnO2) is a naturally occurring soil and sediment component that
      has been shown to oxidize organic compounds containing phenolic or aniline
      moieties. In this study, for the first time we explored the oxidation reaction of
      tetrabromobisphenol A (TBBPA), the most heavily used brominated flame retardant,
      with MnO2. TBBPA rapidly dissipated from the reaction solution and the process
      was accompanied by the dissolution of Mn2+. Dissipation of 50% of TBBPA occurred
      in less than 5 min in a system (pH 4.5) containing 625 microM MnO2 and 3.50
      microM TBBPA at 21 degrees C, and the removal further increased to as high as 90%
      when the reaction was prolonged to 60 min. Analysis of initial reaction kinetics
      showed that the reaction orders with respect to TBBPA, MnO2, and H+ were 1.0,
      0.8, and 0.25, respectively. Higher initial concentrations of TBBPA and MnO2 both
      enhanced the reaction. In addition, reaction rates increased as pH decreased. A
      retarded first-order model was found to closely describe the long-term reaction
      kinetics (R2 > or = 0.99), from which initial half-lives of TBBPA under different
      reaction conditions were estimated. A total of 7 reaction products were
      identified and a tentative reaction scheme was proposed. This study suggests that
      oxidative transformation of TBBPA by MnO2 may play an important role in the
      natural attenuation of TBBPA. The reaction may be further optimized for treatment
      of TBBPA-containing wastewater or remediation of TBBPA-polluted environmental
      matrices.

PMID- 19603666
TI  - Oil industry wastewater treatment with fouling resistant membranes containing
      amphiphilic comb copolymers.
AB  - The oil industry produces large volumes of wastewater, including oil well
      produced water brought to the surface during oil drilling, and refinery
      wastewater. These streams are difficult to treat due to large concentrations of
      oil. Ultrafiltration (UF) is very promising for their treatment to remove oil,
      but has been limited by economic obstacles due to severe membrane fouling. In a
      recent study, novel UF membranes incorporating the amphiphilic comb copolymer
      additive polyacrylonitrile-graft-poly(ethylene oxide), PAN-g-PEO, were found to
      exhibit complete resistance to irreversible fouling by several classes of organic
      foulants (J. Membr. Sci. 2007, 298, 136-146). The current work focuses on
      application of these novel UF membranes to the treatment of oily wastewater feed
      streams, employing three industrial samples of oil well produced water and
      refinery wastewater. UF membranes cast with 20 wt % PAN-g-PEO in PAN achieved
      removals of dispersed and free oils of over 96% based on chemical oxygen demand
      (COD) for produced water samples, comparable to a PAN UF commercial membrane
      control. For refinery wastewater treatment the COD removal values were
      substantially lower, between 41 and 44%, due to higher contents of dissolved
      organics. Comb copolymer modified membranes showed significantly better fouling
      resistance than controls, recovering fully their initial fluxes after a simulated
      backwash for each of the three wastewater samples tested. The results indicate
      that UF membranes incorporating PAN-g-PEO can be cleaned completely by physical
      methods alone, which should extend membrane lifetimes substantially and improve
      the process economics for treatment of oil-contaminated waters.

PMID- 19603667
TI  - Ultrasound-assisted plasma: a novel technique for inactivation of aquatic
      microorganisms.
AB  - Nonthermal plasma and ultrasound are two techniques capable of microorganism
      inactivation in a liquid phase. However, the interaction between the two
      techniques is not yet understood. In this study, an ultrasound-assisted plasma
      (USaP) technique by combining the two means is proposed. A lab-scale USaP system
      was designed and experimentally tested. The inactivation experiments were
      conducted with various conditions of two types of electrode layout (submerged and
      hybrid reactors), aeration or not, and two microorganism species E. coli and
      yeast. For a 30-min treatment, the inactivation efficiencies with no aeration
      were 2-, 2-, and 6-log reductions for ultrasound, plasma, and ultrasound-assisted
      plasma, respectively; and with aeration were 2-, 6-, and 6-log reductions,
      respectively. The aeration greatly enhanced the inactivation efficiency for the
      plasma but not for the ultrasound or the ultrasound-assisted plasma. The
      influences of electrode layout and microorganism species were insignificant on
      the inactivation efficiency. On the other hand, for a submerged reactor without
      aeration, the inactivation efficiency achieved with ultrasound-assisted plasma
      (eta(USaP)) was not only greater than eta(ultasound) or eta(plasma), but also
      greater than the summation of eta(ultrasound and eta(plasma). Namely, a
      synergistic effect of ultrasound-plasma combination on the inactivation was
      observed. No such synergistic effect was observed in a hybrid reactor or in
      aeration cases. The synergism is speculatively a virtue of the ultrasonic
      generated bubbles that easily induce plasma discharges, and thus enhance
      microorganism inactivation in water.

PMID- 19603668
TI  - Fugitive emissions from liquid-charged flange joints: a comparison of laboratory
      and field data.
AB  - Starting from Hagen-Poiseuille's law, we analyzed the parameters influencing
      fugitive emission rates. It is shown that liquid and gas emissions follow
      basically different mass transport mechanisms so that mathematical models
      available for gases are not suitable to calculate liquid emissions. The emission
      behavior of liquid-charged flange joints is characterized, and a model conception
      for the observed phenomena is presented explaining the unexpectedly high
      emissions of liquid-charged flange joints. Against the background of field data,
      the influence of maintenance on fugitive emmissions is demonstrated, and
      exchanging old gaskets with high-grade gaskets as a means of emission reduction
      in old plants is critically scrutinized. A general maintenance plan is proposed
      as the most effective method for emission reductions.

PMID- 19603669
TI  - Evaluation of SBRC-gastric and SBRC-intestinal methods for the prediction of in
      vivo relative lead bioavailability in contaminated soils.
AB  - In this study, lead (Pb) bioaccessibility in contaminated soils was assessed
      using an in vitro method (SBRC) encompassing gastric (SBRC-G) and intestinal
      (SBRC-I) phases. Initially, bioaccessibility studies were performed with a Pb
      reference material (Pb acetate, 1-10 mg L(-1)) in order to determine the
      influence of pH on Pb solubility. In the gastric phase (pH 1.5), Pb solubility
      was 100% (100 +/- 2.9%, n = 16) irrespective of the Pb concentration added,
      however, when the pH of the intestinal phase was increased to near neutral, Pb
      solubility decreased to 14.3 +/- 7.2%. In contaminated soils, Pb bioaccessibility
      varied from 35.7 to 64.1% and 1.2 to 2.7% for SBRC-G and SBRC-I phases,
      respectively. When relative bioaccessibility (Rel-SBRC-I) was calculated by
      adjusting the dissolution of Pb from contaminated soils by the solubility of Pb
      acetate at pH 6.5 (intestinal phase pH); Rel-SBRC-I values ranged from 11.7
      26.1%. A stepwise regression model based on Pearson correlation factors was used
      to determine the suitability of in vitro assays for predicting in vivo (swine
      assay) relative Pb bioavailability. Rel-SBRC-I provided the best estimate of in
      vivo relative Pb bioavailability for soils used in this study (in vive relative
      Pb bioavailability [%] = Rel-SBRC-I [pH 6.5%] x 0.58 + 1.98, P = 0.53). The
      versatility of Rel-SBRC-I was demonstrated by accurately predicting relative Pb
      bioavailability from other reported in vivo studies.

PMID- 19603670
TI  - Do acid volatile sulfides (AVS) influence the accumulation of sediment-bound
      metals to benthic invertebrates under natural field conditions?
AB  - The present study evaluates the influence of acid volatile sulfides (AVS) on
      accumulation of sediment-bound metals in benthic invertebrates under natural
      field conditions. Natural sediments, pore water, surface water, and two species
      of widespread benthic invertebrates (Chironomus gr. thummi and Tubifex tubifex)
      were collected from 17 historical polluted Flemish lowland rivers and measured
      for metal concentrations. Different sediment characteristics were determined
      (AVS, organic matter, clay content) and multiple regression was used to study
      their relationship with accumulated metals in the invertebrates. Physical and
      chemical analysis of the field samples indicated low metal concentrations in the
      water and pore water, but very high metal concentrations in the sediment and the
      invertebrates, especially for Pb (5.99 micromol/ g). In general, metal
      accumulation in chironomids and tubificid worms was most strongly correlated with
      total metal concentrations in the sediment and sediment metal concentrations
      normalized for organic matter and clay content. Following the results of the
      linear regression model, AVS did not turn out to be a significant variable in
      describing variation in metal accumulation. Our study clearly demonstrates that,
      in addition to the results gained from experiments under lab conditions, benthic
      invertebrates can accumulate metals from unspiked field sediments even when
      there's an excess of AVS.

PMID- 19603671
TI  - Temperature-dependent bioaccumulation of polycyclic aromatic hydrocarbons.
AB  - Bioaccumulation factors (BAFs) play a key role in risk assessment of chemicals in
      sediments and soils. For hydrophobic organic chemicals (HOCs), BAFs are, however,
      difficult to determine and values are mostly obtained by modeling. Apart from a
      lack of reliable data, the applicability of lab-derived values in the field
      situation is unknown, as exposure conditions (e.g., temperature, pH, salinity,
      test species, number of chemicals) are standardized in the lab, whereas they may
      vary in the field. In this study, the effect of temperature on the
      bioaccumulation of a series of moderate to very hydrophobic PAHs in aquatic worms
      was studied by using polydimethylsiloxane (PDMS)-coated solid phase
      microextraction (SPME) fibers. The results indicated that bioaccumulation of
      nonmetabolizable HOCs is an exothermic, enthalpy-driven process, thus decreasing
      with increasing temperature. As such, biotic concentrations may be several times
      higher in winter than in summertime, which could have ecotoxicological
      consequences. A two-parameter linear free energy relationship was derived with
      which PAH bioaccumulation can be predicted from temperature and the chemicals'
      hydrophobicities. Comparing the determined (thermodynamics of) PAH partitioning
      into organisms and PDMS indicated that the latter phase cannot be used as a
      surrogate phase for animal lipids. Still, SPME provides an appropriate analytical
      tool for the measurement of aqueous concentrations, from which bioaccumulation
      can subsequently be estimated by using BAFs.

PMID- 19603672
TI  - Assessment of oral bioaccessibility of organochlorine pesticides in soil using an
      in vitro gastrointestinal model.
AB  - A static in vitro gastrointestinal model was used to investigate the oral
      bioaccessibility of organochlorine pesticides (OCPs) including
      hexachlorocyclohexane isomers (HCHs) and dichlorodiphenyltrichloroethane and
      metabolites in contaminated soils with different organic matter contents. A key
      hypothesis tested was that a fraction of the mobilized contaminants is sorbed on
      the solid after digestion, and this fraction could be desorbed and become
      bioaccessible in the intestinal tract due to absorption of the dissolved fraction
      by the small intestine. The bioaccessibility would be underestimated if the
      sorbed fraction was separated from the fluid by centrifugation or filtration in
      an in vitro test. In our experiment, a procedure using multiple fluid-to-solid
      ratios was developed to characterize the sorption. It was found that 8-38% of the
      mobilized OCPs were sorbed on the residue and remained in the solid phase after
      the separation. Taking into consideration the sorbed fraction, the measured
      bioaccessibilities of the OCPs varied from 4% to 97% depending on the properties
      of the soils and the compounds. The enantiomeric ratios of chiral compounds
      studied were also determined to distinguish biotic (enzymatic) and abiotic
      (chemical extraction) processes in the in vitro digestion model. It was found
      that although alpha-HCH in the raw soils was racemic, (+)-alpha-HCH was enriched
      in the gastric digestive fluid but depleted in the intestinal digestive fluid.

PMID- 19603673
TI  - Impact of silver nanoparticle contamination on the genetic diversity of natural
      bacterial assemblages in estuarine sediments.
AB  - Recent advancements in the nanotechnology industry have seen a growing interest
      in integrating silver nanoparticles (Ag-NPs) into consumer and medical products.
      To date, there has been little research into the toxicological impact that Ag-NPs
      will have when they enter the marine realm. Of particular concern are the
      possible effects of Ag-NPs on natural bacterial assemblages, given the
      antimicrobial activity of silver. In this study, estuarine sediment samples were
      dosed in triplicate for 20 days from a stock solution of Ag-NPs, with a final
      cumulative treatment of either 0 microg L(-1) (control), 25 microg L(-1) or 1000
      microg L(-1). The experimental tanks were left for a further 10 days to allow for
      any recovery. Inductively coupled plasma-optical emission spectrometery (ICP-OES)
      of water and sediment samples confirmed that the Ag-NPs concentration in the
      aqueous phase decreased after each dosing and were transported to accumulate in
      the surface layer of the sediment (approximately top 3 mm). The overall
      concentration of Ag-NPs in the water column, however, increased steadily during
      the 20 days of dosing but decreased rapidly during the following 10 days without
      dosing. Nevertheless, the Ag-NPs did not have any impact on the prokaryotic
      abundance in the water column over the incubation period (ANOVA, P < 0.05).
      Environmental DNA was extracted from sediment samples and a two-step nested PCR
      denaturing gradient gel electrophoresis (DGGE) approach, using PCR primers
      specific to the phylum Bacteria, was adopted to assess their diversity.
      Multivariate statistical analyses of presence/ absence matrices produced from
      DGGE profiles revealed negligible differences in bacterial diversity between
      treatments, suggesting that, under the selected experimental regime, Ag-NPs
      present little or no impact on estuarine sediment bacterial diversity. Possible
      reasons for this could include environmental factors, in particular the chloride
      ions in estuary water affecting the chemistry and behavior of Ag-NPs.

PMID- 19603674
TI  - Fate and effects of CeO2 nanoparticles in aquatic ecotoxicity tests.
AB  - Cerium dioxide nanoparticles (CeO2 NPs) are increasingly being used as a catalyst
      in the automotive industry. Consequently, increasing amounts of CeO2 NPs are
      expected to enter the environment where their fate in and potential impacts are
      unknown. In this paper we describe the fate and effects of CeO2 NPs of three
      different sizes (14, 20, and 29 nm) in aquatic toxicity tests. In each standard
      test medium (pH 7.4) the CeO2 nanoparticles aggregated (mean aggregate size
      approximately 400 nm). Four test organisms covering three different trophic
      levels were investigated, i.e., the unicellular green alga Pseudokirchneriella
      subcapitata, two crustaceans: Daphnia magna and Thamnocephalus platyurus, and
      embryos of Danio rerio. No acute toxicity was observed for the two crustaceans
      and D. rerio embryos, up to test concentrations of 1000, 5000, and 200 mg/L,
      respectively. In contrast, significant chronic toxicity to P. subcapitata with
      10% effect concentrations (EC10s) between 2.6 and 5.4 mg/L was observed. Food
      shortage resulted in chronic toxicity to D. magna, for wich EC10s of > or = 8.8
      and < or = 20.0 mg/L were established. Chronic toxicity was found to increase
      with decreasing nominal particle diameter and the difference in toxicity could be
      explained by the difference in surface area. Using the data set, PNEC(aquatic)S >
      or = 0.052 and < or = 0.108 mg/L were derived. Further experiments were performed
      to explain the observed toxicity to the most sensitive organism, i.e., P.
      subcapitata. Toxicity could not be related to a direct effect of dissolved Ce or
      CeO2 NP uptake or adsorption, nor to an indirect effect of nutrient depletion (by
      sorption to NPs) or physical light restriction (through shading by the NPs).
      However, observed clustering of NPs around algal cells may locally cause a direct
      or indirect effect.

PMID- 19603675
TI  - Occurrence and potential significance of perfluorooctanoic acid (PFOA) detected
      in New Jersey public drinking water systems.
AB  - After detection of perfluorooctanoic acid (PFOA) in two New Jersey (NJ) public
      water systems (PWS) at concentrations up to 0.19 microg/L, a study of PFOA in 23
      other NJ PWS was conducted in 2006. PFOA was detected in 15 (65%) of the systems
      at concentrations ranging from 0.005 to 0.039 microg/L. To assess the
      significance of these data, the contribution of drinking water to human exposure
      to PFOA was evaluated, and a health-based drinking water concentration protective
      for lifetime exposure of 0.04 microg/L was developed through a risk assessment
      approach. Both the exposure assessment and the health-based drinking water
      concentrations are based on the previously reported 100:1 ratio between the
      concentration of PFOA in serum and drinking water in a community with highly
      contaminated drinking water. The applicability of this ratio to lower drinking
      water concentrations was confirmed using data on serum levels and water
      concentrations from other communities. The health-based concentration is based on
      toxicological end points identified by U.S. Environmental Protection Agency
      (USEPA) in its 2005 draft risk assessment Recent information on PFOA's toxicity
      not considered in the USEPA risk assessment urther supports the health-based
      concentration of 0.04 microg/L. In additional sampling of 18 PWS in 2007-2008,
      PFOA in most systems was below the health-based concentration. However, PFOA was
      detected above the health-based concentration in five systems, including one not
      previously sampled.

PMID- 19603676
TI  - Oxidative stress induced by zero-valent iron nanoparticles and Fe(II) in human
      bronchial epithelial cells.
AB  - To identify the mechanism through which nanoparticulate zero-valent iron (nZVI;
      Fe0(s)) damages cells, a series of experiments were conducted in which nZVI in
      phosphate-buffered saline (PBS) was exposed to oxygen in the presence and absence
      of human bronchial epithelial cells. When nZVI is added to PBS, a burst of
      oxidants is produced as Fe0 and ferrous iron (Fe[II]) are converted to ferric
      iron (Fe[II]). Cytotoxicity and internal reactive oxygen species (ROS) production
      in cells exposed to nZVI is equivalent to the response observed when cells are
      exposed to the same concentration of dissolved Fe(II). Experiments conducted in
      the absence of cells indicate that the oxidant produced during Fe(II) oxidation
      reacts with methanol and dimethyl sulfoxide, but not with compounds such as tert
      butanol and benzoate that react exclusively with hydroxyl radical. The role of
      reactive oxidants produced during Fe(II) oxidation in cytotoxicity and internal
      ROS production is further supported by experiments in which cell damage was
      limited by the addition of ligands that prevented Fe(II) oxidation and by the
      absence of cell damage when the nanoparticles were oxidized prior to exposure.
      The behavior of the oxidant produced by nZVI is consistent with an oxidant such
      as the ferryl ion, rather than hydroxyl radical.

PMID- 19603677
TI  - Analysis of nine NSAIDs in ungulate tissues available to critically endangered
      vultures in India.
AB  - In 2006, India, Pakistan, and Nepal banned the manufacture of veterinary
      formulations of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac. This
      action was taken to halt the unprecedented decline of three Gyps vulture species
      that were being poisoned by diclofenac residues commonly present in carcasses of
      domestic livestock upon which they scavenged. To assess the affect of this ban
      and evaluate residue prevelances of other NSAIDs, we present a method to detect
      diclofenac and eight more NSAIDs by liquid chromatography-mass spectrometry and
      apply this to 1488 liver samples from carcasses of livestock taken across seven
      Indian states. Diclofenac was present in 11.1% of samples taken between April and
      December 2006, and meloxicam (4%), ibuprofen (0.6%), and ketoprofen (0.5%) were
      also detected. Although meloxicam is safe for a range of avian scavengers,
      including Gypsvultures, data regarding the safety of other NSAIDs is currently
      limited. If wild Gyps on the Indian subcontinent are to survive, diclofenac bans
      must be completely effective, and NSAIDs that replace it within the veterinary
      drug market must be of low toxicity toward Gyps and other scavenging birds.

PMID- 19603678
TI  - Relation between urinary metabolites of polycyclic aromatic hydrocarbons and
      human semen quality.
AB  - Most of the general populations are exposed to polycyclic aromatic hydrocarbons
      (PAHs) at different levels. A limited number of studies have suggested that PAHs
      exposure may be associated with semen quality. To examine the association of four
      PAH metabolites, 1-hydroxynapthalene (1-N), 2-hydroxynapthalene (2-N), 1
      hydroxypyrene (1-OHP) and 2-hydroxyfluorene (2-OHF) with altered semen quality,
      542 subjects were recruited through the clinic following strict eligibility
      screening. Using LC-MS/MS, individual exposures were measured as spot urinary
      concentrations of PAH metabolites adjusted by creatinine (CR). Semen quality was
      assessed by semen volume, sperm concentration, sperm number per ejaculum, and
      sperm motility. First, we confirmed the variability of PAH metabolites in human
      urine. Our results showed that the median CR-adjusted concentrations of 1-N, 2-N,
      1-OHP, 2-OHF were 2.35, 4.05, 1.14, and 2.89 microg/g of CR, respectively.
      Significant P-values for trend were found that men with higher 1-OHP (assessed as
      quintiles) were more likely to have below-reference sperm concentration and sperm
      number per ejaculum. These results indicate that PAHs exposure might be related
      to altered human semen quality.

PMID- 19603679
TI  - Prokaryotic real-time gene expression profiling for toxicity assessment.
AB  - Examining global effects of toxins on gene expression profiles is proving to be a
      powerful method for toxicity assessment and for investigating mechanisms of
      toxicity. This study demonstrated the application of prokaryotic real-time gene
      expression profiling in Escherichia coli for toxicity assessment of environmental
      pollutants in water samples, by use of a cell-array library of 93 E. coli K12
      strains with transcriptional green fluorescent protein (GFP) fusions covering
      most known stress response genes. The high-temporal-resolution gene expression
      data, for the first time, revealed complex and time-dependent transcriptional
      activities of various stress-associated genes in response to mercury and
      mitomycin (MMC) exposure and allowed for gene clustering analysis based on
      temporal response patterns. Compound-specific and distinctive gene expression
      profiles were obtained for MMC and mercury at different concentrations. MMC
      (genotoxin) induced not only the SOS response, which regulates DNA damage and
      repair, but also many other stress genes associated with drug
      resistance/sensitivity and chemical detoxification. A number of genes belonging
      to the P-type ATPase family and the MerR family were identified to be related to
      mercury resistance, among which zntA was found to be up-regulated at an
      increasing level as the mercury concentration increased. A mechanism-based
      evaluation of toxins based on real-time gene expression profiles promises, to be
      an efficient and informative method for toxicity assessment in environmental
      samples.

PMID- 19603680
TI  - Measurement of personal exposure to volatile organic compounds and particle
      associated PAH in three UK regions.
AB  - Personal exposures to 15 volatile organic compounds (VOC) and 16 polycyclic
      aromatic hydrocarbons (PAH) of 100 adult nonsmokers living in three UK areas,
      namely London, West Midlands, and rural South Wales, were measured using an
      actively pumped sampler carried around by the volunteers for 5/1 (VOC/PAH)
      consecutive 24-h periods, following their normal lifestyle. Results from personal
      exposure measurements categorized by geographical location, type of dwelling, and
      exposure to environmental tobacco smoke (ETS) are presented. The average personal
      exposure concentration to benzene, 1,3-butadiene, and benzo(a)pyrene representing
      the main carcinogenic components of the VOC and PAH mixture were 2.2 +/- 2.5
      microg/m3, 0.4 +/- 0.7 microg/m3, and 0.3 +/- 0.7 ng/m3 respectively. The
      association of a number of generic factors with personal exposure concentrations
      was investigated, including first-line property, traffic, the presence of an
      integral garage, and ETS. Only living in houses with integral garages and being
      exposed to ETS were identified as unequivocal contributors to VOC personal
      exposure, while only ETS had a clear effect upon PAH personal exposures. The
      measurements of personal exposures were compared with health-based European and
      UK air quality guidelines, with some exceedences occurring. Activities
      contributing to high personal exposures included the use of a fireplace in the
      home, ETS exposure, DIY (i.e., construction and craftwork activities), and
      photocopying, among others.

PMID- 19603681
TI  - Observation of a commercial fluorinated material, the polyfluoroalkyl phosphoric
      acid diesters, in human sera, wastewater treatment plant sludge, and paper
      fibers.
AB  - Sources of human exposure to perfluorinated carboxylic acids (PFCAs) are not well
      characterized. Polyfluoroalkyl phosphoric acids (PAPs) are fluorinated
      surfactants used in human food contact paper products. PAPs can migrate into food
      and food simulants, and their bioavailability and biotransformation into PFCAs
      has been demonstrated using a rat model. To characterize human exposure to PAP
      materials, we analyzed pooled human sera samples collected in 2004 and 2005 (n =
      10) and 2008 (n = 10) from the midwestern United States for the 4:2 through 10:2
      PAP diesters (diPAPs). The 2004 and 2005 sera samples contained 4.5 microg/L
      total diPAPs, with the 6:2 diPAP dominating the congener profile at 1.9 +/- 0.4
      microg/L DiPAP concentrations observed in the 2004 and 2005 human sera samples
      were similar to those of the C8 to C11 PFCAs (0.13 +/- 0.01 to 4.2 +/- 0.3
      microg/L) monitored in the same samples. 6:2 diPAP was also consistently observed
      in the 2008 human sera samples at a mean concentration of 0.63 +/- 0.13 microg/L
      As diPAPs have been shown to degrade to PFCAs in vivo, our observation of diPAPs
      in human sera may be a direct connection between the legacy of human PFCA
      contamination and PAPs commercial applications. Wastewater treatment plant (WWTP)
      sludge and paper fibers were analyzed for diPAPs as a proxy for human use and
      potential exposure to diPAPs. DiPAPs were observed in WWTP sludge at
      concentrations ranging from 47 +/- 22 to 200 +/- 130 ng/g, a range similar to
      perfluorooctane sulfonic acid (PFOS) (100 +/- 70 ng/g) and greater than the C8 to
      C11 PFCAs (1.6 +/- 0.6 to 0.17 +/- 0.10 ng/g) observed in the same samples.
      DiPAPs were observed in paper fiber extracts at concentrations ranging from 34 +/
      30 to 2200 +/- 400 ng/g. The high diPAP concentrations in WWTP sludge suggest
      PAP materials may be prevalent in our daily lives.

PMID- 19603682
TI  - Direct particle-to-cell deposition of coarse ambient particulate matter increases
      the production of inflammatory mediators from cultured human airway epithelial
      cells.
AB  - Exposure of cultured cells to particulate matter air pollution is usually
      accomplished by collecting particles on a solid matrix, extracting the particles
      from the matrix, suspending them in liquid, and applying the suspension to cells
      grown on plastic and submerged in medium. The objective of this work was to
      develop a more physiologically and environmentally relevant model of air
      pollutant deposition on cultures of human primary airway epithelial cells. We
      hypothesize that the toxicology of inhaled particulate matter depends strongly on
      both the particulate dispersion state and the mode of delivery to cells. Our
      exposure system employs a combination of unipolar charging and electrostatic
      force to deposit particles directly from the air onto cells grown at an air
      liquid interface in a heated, humidified exposure chamber. Normal human bronchial
      epithelial cells exposed to concentrated, coarse ambient particulate matter in
      this system expressed increased levels of inflammatory biomarkers at 1 h
      following exposure and relative to controls exposed to particle-free air. More
      importantly, these effects are seen at particulate loadings that are 1-2 orders
      of magnitude lower than levels applied using traditional in vitro systems.

PMID- 19603683
TI  - Intermittent energy harvesting improves the performance of microbial fuel cells.
AB  - In this study, we compare the efficiencies of harvesting energy from microbial
      fuel cells (MFC) using two modes of operation: (1) continuous-passing the current
      through an electrical load-and (2) intermittent-first accumulating the energy in
      a capacitor and then discharging it through the load. Each of these two modes of
      operation has advantages and disadvantages: the first mode of operation allows
      the continuous powering of low-power-consuming devices, and the second mode of
      operation allows the intermittent powering of high-power-consuming devices. We
      used a two-compartment MFC: in the anodic compartment, Shewanella oneidensis MR-1
      was grown using lactate as an electron donor, whereas in the cathodic compartment
      we used an electrode made of manganese-based catalyzed carbon bonded to a current
      collecting screen made of platinum mesh and oxygen as the electron acceptor. The
      maximum power generated by harvesting energy intermittently was 152 microW, which
      is 111% higher than the 72 microW generated by harvesting the energy
      continuously. We conclude that in the operation of MFCs it is beneficial to
      harvest the energy intermittently. This not only allows the powering of external
      devices of high power consumption but also allows generating power with greater
      energy efficiency than does harvesting the energy continuously.

PMID- 19603684
TI  - Photocatalytic oxidation of Escherischia coli, Aspergillus niger, and
      formaldehyde under different ultraviolet irradiation conditions.
AB  - Ultraviolet (UV) light irradiation, including the type of light source, light
      intensity, and irradiation dosage, directly affects the photocatalytic reaction
      rate and energy consumption. In this study, we investigated the photocatalysis
      effect of decomposing organic matter and inactivation bacteria and fungi under
      various conditions of UV sources (UVA and UVC) and light intensities (from 0.01
      to 10 W/m2). The effect of light intensity was evaluated by photocatalytic
      reaction rate and UV dosage defined as a product of light intensity and
      irradiation time necessary to achieve a certain reduction. The results confirmed
      the positive effect of increased light intensity on photocatalytic reactions and
      suggested that within the light intensity range applied in this study low light
      intensity with long exposure time has higher light utilization efficiency
      compared to that of high light intensity with short exposure time. A conception
      for selection of the appropriate light intensity and dosage for effective
      degradation of pollutants, while saving energy, was provided.

PMID- 19603685
TI  - Bullying in healthcare: strategies for combating disruptive behaviors.

PMID- 19603686
TI  - A plan for identification, treatment, and remediation of disruptive behaviors in
      physicians.
AB  - Physicians exhibiting a pattern of disruptive conduct represent a small portion
      of all healthcare professionals. Available evidence demonstrates, however, that
      their behaviors can result in increased workplace stress; contribute to poor
      workplace environments; contribute to dysfunctional teams; reduce quality of care
      for patients and families; and increase risk of litigation for hospitals and
      institutions. Our experience at Vanderbilt reveals that both internal and
      external factors play a role in a physician's behavior and ability to cope with
      workplace stresses. We have gained valuable insight into various means of
      indentifying, assessing, treating, and remediating physicians exhibiting
      unprofessional behavior. The vast majority of healthcare team members conduct
      themselves professionally and without complaint. This paper will demonstrate how
      to address those rare individuals who exhibit disruptive and/or unprofessional
      behavior.

PMID- 19603687
TI  - Bullying, incivility, and disruptive behaviors in the healthcare setting:
      identification, impact, and intervention.
AB  - Bullying, incivility, and their associated disruptive behaviors are insidious and
      destructive forces with negative consequences that require identification and
      intervention at the individual and organizational level. Costs incurred secondary
      to these insensitive behaviors are substantial and involve matters of patient
      safety, absenteeism, turnover, turnover intentions, organizational commitment,
      and employee healthcare. Factors that increase the risk of hostile behaviors
      include changing hierarchies, conflicting loyalties, stress, and the state of the
      science. Each organization has the responsibility to develop processes for
      managing threatening and intimidating actions. New criteria are proposed to guide
      the implementation of successful programs.

PMID- 19603688
TI  - Teaching respect at Maimonides Medical Center.

PMID- 19603689
TI  - Understanding and responding to bullying and related behaviors in healthcare
      workplaces.

PMID- 19603690
TI  - [Survivability of Candida fungi and workpost safety in the university mycological
      laboratory].
AB  - BACKGROUND: To ensure the security for persons using the laboratory for research
      purposes it was decided to determine the influence of the number of employees and
      the time of their work on the survivability and vitality of Candida albicans, C.
      dubliniensis and C. tropicalis. MATERIAL AND METHODS: Working time and the number
      of people in the room were monitored. Temperature and air relative humidity were
      checked. Every two weeks the vitality and survivability of fungi were assessed
      with the technique of intravital coloring in methylene blue. RESULTS: During the
      observation of the examined species no 100% mortality was noted. After half a
      year of observation, the percentage of living cells in the smear did not exceed
      10%. The greatest fluctuations in the survivability and its lowest value (5%)
      were found in C. albicans in the drop. The mortality rate in similar trials did
      not exceed 30% in C. dubliniensis and C. tropicalis isolates. CONCLUSIONS: To
      secure the protection of employees one should limit the number of people entering
      the laboratory, use face masks, refresh archival isolate, and monitor hygiene
      procedures twice a year, depending on the frequency of changing objects and
      research team.

PMID- 19603691
TI  - [Tobacco smoking and other negative lifestyle behaviors among economically active
      individuals].
AB  - BACKGROUND: Tobacco smoking, lack of recreational physical activity, unbalanced
      diet, overweight and obesity are the major modifiable risk factors for chronic
      diseases. The aim of the study was to evaluate the prevalence of smoking and the
      other lifestyle behaviors among economically active adults. MATERIAL AND METHODS:
      The study population consisted of 442 randomly selected economically active
      adults from the Lodz and Lublin districts, Poland. The prevalence and different
      possible combination of four major risk factors for chronic diseases was
      determined. RESULTS: About 40% of men and 28% of women smoke at least one
      cigarette per day. Only 3.5% of men and 1.9% of women meet the recommended
      guidelines for four common health life style factors. Only about 2% of smokers
      obey the rules relating to other healthy behaviors. In women smoking cigarettes,
      the risk for not being physically active is twice as high as that in nonsmokers.
      CONCLUSIONS: The prophylactic programs for healthy lifestyle behaviors should be
      addressed to all economically active individuals, taking into account their level
      of education, the type of work performed and income.

PMID- 19603692
TI  - [Exposure to environmental tobacco smoke and psychomotor development of
      children].
AB  - BACKGROUND: In Poland, prenatal exposure to tobacco smoke is observed in about 30
      percent of children and postnatal in over 50 percent of children. This exposure
      has serious health consequences, including the negative effect on child
      neurodevelopment. The aim of the study was to assess the effect of environmental
      tobacco smoke (ETS) exposure on child psychomotor development. MATERIAL AND
      METHODS: The study population consisted of 63 children with well assessed
      prenatal ETS exposure (a threefold analysis of cotinine level in saliva of
      pregnant women). To assess ETS exposure in infants within one year after birth a
      questionnaire-based interview was conducted with mothers. The Bayley Scale for
      Infant and Toddler Development (BESID-III) was used for the evaluation of child
      neurodevelopment. RESULTS: Multivariate analysis (including gender, birth order
      of the child and parental educational status) indicated the statistically
      significant association between prenatal exposure to ETS and cognitive child
      development (b = -4.0; p = 0.04). ETS exposure has also a negative impact on
      motor (b = -2.7; p = 0.2) and language (b = -3.4; p = 0.08) abilities of the
      child although the results were not statistically significant. CONCLUSIONS:
      Maternal smoking was found to be related to a decrease in child neurodevelopment,
      however, it was impossible to separate the prenatal from postnatal exposure. A
      lot of effort should be made to eliminate ETS exposure of children.

PMID- 19603693
TI  - [Changes in behavior related to tobacco smoking ten years after joining the "Quit
      and win" competition in the groups under additional intervention program].
AB  - BACKGROUND: International anti-nicotine campaigns have been found to be efficient
      and economically effective methods of reducing tobacco addiction on a social
      scale. Nevertheless innovative methods are being looked for in order to increase
      the efficiency of anti-nicotine interventions. The aim of the research was to
      evaluate a long-term efficiency of two programs of additional anti-nicotine
      intervention introduced after the 2nd International Antinicotine Campaign
      conducted in Poland (1996) in two randomly chosen groups of people from among the
      participants of the 'Quit and Win' competition held in 1996. MATERIALS AND
      METHODS: The two programs of additional intervention differed in their substance
      and economic terms. For 10 years (June 1996-August 2006), the efficiency of the
      programs had been systematically evaluated. The study was carried out in two
      experimental groups, one comprised 222 and the other 242 participants of the 1996
      competition, and the control group consisting of 224 participants of the same
      competition. RESULTS: In the first experimental group, 53 (23.9%) persons
      responding to s the questions concerning tobacco smoking between January and
      July, 2006 reported that they had not smoked a single cigarette, and in the
      second experimental group, 72 (29.8%) persons reported complete abstinence from
      smoking in that period In the control group, 53 respondents (23.7%) stated that
      they had not smoked at all in the aforesaid period of time. CONCLUSIONS: One of
      the used programs of the additional anti-nicotine intervention, which proved to
      be less expensive contributed to achieving a far better long-term results of the
      campaign.

PMID- 19603694
TI  - [Tobacco smoking among young patients with bronchial asthma and determination of
      smoking-related behavior in the patient's closest environment].
AB  - BACKGROUND: The negative influence of tobacco smoke on the course of bronchial
      asthma is complex and includes direct toxic effects on the epithelium of the
      respiratory tract. It is estimated that in developed countries, approximately 25
      percent of adult asthmatics are tobacco smokers. Knowledge of the scale of the
      habit, may considerably contribute to the optimization of effective pro-health
      activity. The aim of this study was to analyze the occurrence of tobacco smoking
      among patients with the respiratory system disease. MATERIAL AND METHODS: The
      study group comprised 371 patients (136 men and 235 women, aged 18-30) with
      diagnosed bronchial asthma and treated in the Allergy Outpatient Clinic in
      Swiecie, Poland. They were subjected to an analysis aimed at determining the
      reasons for tobacco smoking and smoking-related behavior in the patient's closest
      environment. RESULTS: In the examined group, there were 92 tobacco smokers (63
      men and 29 women). The multi-variant analysis showed that hanging around smoking
      friends, the pleasure of smoking and experienced relaxation were the most
      frequent motivation for taking up smoking. Similar reasons, hanging around
      smoking friends, group acceptance, and pleasure of smoking, were reported by
      59.8%, 43.5%, and 43.5% of patients, respectively. The behavior of people in the
      closest environment influenced the majority of smokers with asthma; 80% of
      patients reported current smoking and 88% of patients in medical history. The
      proportion of non-smokers was 47 and 34%, respectively. CONCLUSION: To sum up, it
      should be stated that despite of the fact that smoking is a documented risk
      factor, young patients with bronchial asthma are still subjected to this habit.

PMID- 19603695
TI  - [Evaluation of occupational medicine service tasks in the context of the
      Occupational Medicine Service Act, article 12, on the basis of statistical
      indicators in the Pomorskie voivodship].
AB  - BACKGROUND: Occupational health service is based on legal regulations. We have
      made an attempt to estimate the implementation of the tasks resulting from
      article 12 of the Occupational Medicine Service Act introduced in 1998. MATERIALS
      AND METHODS: In this paper we analyzed statistical data concerning the number of
      prophylactic health contracts, economic entities and health insurance payers. The
      data come from the Nofer Institute of Occupational Medicine, Central Statistical
      Office and Social Insurance Institution. RESULTS: Contract Coverage Rate (CCR)
      has been introduced for the purpose of this research. The data show that in 2007,
      the Contract Coverage Rate (CCR) for the Pomorskie voivodeship (province)
      accounted for 45.7%, with the median value of 14.4% for all voivodeships in
      Poland. CONCLUSIONS: According to the gathered statistical data, it should be
      concluded that the implementation of article 12 is insufficient. The amendment to
      the Act introducing the provision on written contracts is an opportunity to
      provide an effective mechanism, by which the present situation can be improved
      and the rates raised to a satisfactory level.

PMID- 19603696
TI  - [The influence of electromagnetic fields on flora and fauna].
AB  - This paper presents the influence of natural and artificial electromagnetic
      fields (EMF) on fauna and flora. The mechanisms of Earth's magnetic field
      detection and the use of this skill by migratory animals to faultlessly reach the
      destination of their travel are discussed, as well as the positive effects of
      electric and magnetic fields on plants relative to their physiology, yielding and
      health. EMF influence on social insects and animal organisms, including possible
      DNA damages and DNA repair systems, is presented. The influence of high frequency
      electromagnetic fields on birds nesting is also discussed.

PMID- 19603697
TI  - [Consequences of changed regulations on the protection of the environment against
      the influence of the 50 Hz magnetic field].
AB  - Over the recent years some countries have introduced norms, regulations or
      recommendations limiting the value of few A/m permissible levels of the 50 Hz
      magnetic field (MF) in the environment. This results from the studies indicating
      a number of biological effects on living organisms exposed to magnetic fields
      with levels similar to those produced by high voltage overhead power lines. The
      main objective of these restrictions was to protect human health from the effects
      of MF produced by high voltage overhead transmission lines. The changed
      permissible level of MF intensity to the level now binding in different countries
      will have great economic and financial impact. The greatest impact will be
      observed in the already established residential areas, which require that the
      levels of magnetic field from existing overhead lines be lowered. The effects of
      more strict regulations on the protection against the effects of the 50 Hz
      magnetic field, reducing the levels to values lower than 0.25 A/m, can be grouped
      into three categories: technical effects, space and landscape implications and
      financial impact. The lowering of MF maximum acceptable level will require
      changes in the structure of new power lines and modifications in the existing
      grid. Unfortunately, the replacing of overhead power lines with cables is not
      possible on account of too high costs. The extension of the area, in which
      construction of dwelling houses will not be possible, can turn out to be the only
      solution.

PMID- 19603698
TI  - [Costs and range of health care consumption under general health insurance and
      sick leaves among patients with inflammatory bowel disease in chosen countries --
      a literature review].
AB  - Inflammatory bowel disease (IBD) is considered to be common in the developed
      countries of Europe and in North America. A chronic nature of the disease, bowel
      and systemic symptoms debilitating daily functioning, coexisting extraintestinal
      complications, recurrent, not infrequently severe and unpredictable clinical
      course significantly lower patients' quality of life. When compared with the
      general population, IBD patients more often take use of health care services.
      They also experience more episodes of sick leave, which is associated with a
      greater number of sick leave days per year.

PMID- 19603699
TI  - [15th International Symposium on Ergonomics, Work Safety and Occupational Hygiene
      in Agriculture: identification and methods for reducing the risk of
      musculoskeletal system diseases associated with work in agriculture].

PMID- 19603700
TI  - Improvement of water treatment pilot plant with Moringa oleifera extract as
      flocculant agent.
AB  - Moringa oleifera extract is a high-capacity flocculant agent for turbidity
      removal in surface water treatment. A complete study of a pilot-plant
      installation has been carried out. Because of flocculent sedimentability of
      treated water, a residual turbidity occured in the pilot plant (around 30 NTU),
      which could not be reduced just by a coagulation-flocculation-sedimentation
      process. Because of this limitation, the pilot plant (excluded filtration)
      achieved a turbidity removal up to 70%. A slow sand filter was put in as a
      complement to installation. A clogging process was characterized, according to
      Carman-Kozeny's hydraulic hypothesis. Kozeny's k parameter was found to be 4.18.
      Through fouling stages, this k parameter was found to be up to 6.36. The obtained
      data are relevant for the design of a real filter in a continuous-feeding pilot
      plant. Slow sand filtration is highly recommended owing to its low cost, easy
      handling and low maintenance, so it is a very good complement to Moringa water
      treatment in developing countries.

PMID- 19603701
TI  - Influence of storage methods, refrigeration or freezing, on the toxicity of
      wastewater samples to oyster embryos.
AB  - One of the main concerns in wastewater whole effluent assessment is the sampling
      phase and the sample chain of custody before any toxicity evaluation. The major
      problem is related to establishing the correct method for sample storage in order
      to perform toxicity bioassays. The toxicity of some domestic and glass factory
      industrial wastewater samples stored both by refrigeration at 4 +/- 1 degrees C
      for no more than three days, and freezing at -18 +/- 1 degrees C for no more than
      one month was compared via the embryo larval development bioassay with the oyster
      Crassostrea gigas. The results showed no significant differences between the
      toxicities of refrigerated and frozen wastewater samples. The wastewater
      classification, according to a score based on four toxicity classes, showed that
      the preservation methods did not alter the toxicity classification of the
      samples. In particular, it was demonstrated that the samples considered as 'not
      acutely toxic' after refrigeration were also found to have this classification
      after freezing.

PMID- 19603702
TI  - Trimetallic supported catalyst for renewable source of energy and environmental
      control through CO2 conversion.
AB  - A supported catalyst and a catalytic process have been developed for the
      conversion of carbgas (CO2 + (100 ppm) H2O + 1% H2) as a renewable source of
      energy and as a measure for the control of carbon dioxide -- a greenhouse gas.
      The carbgas was passed over a trimetallic supported catalyst consisting of
      ruthenium (Ru), manganese (Mn) and cobalt (Co) dispersed on a high surface area
      titanium dioxide support at 673 K and at atmospheric pressure with a gas space
      velocity of 6000-7200/h. The catalytic reaction produces methanol and propyne in
      a fixed bed reactor system. The catalyst simultaneously splits water into
      hydrogen and oxygen, and carbon dioxide into carbon and oxygen under very mild
      reaction conditions and at atmospheric pressure. The oxygen generated during the
      reaction and the addition of hydrogen during the catalytic reaction not only
      generates a considerable amount of energy for the reaction to proceed but also
      sustains the oxidation states of Ru, Mn and Co. This process maintains the
      specific active oxidation states of the metals during the catalytic run -- a key
      step in the process.

PMID- 19603703
TI  - Removal of nickel and cadmium from aqueous solutions by sewage sludge ash: study
      in single and binary systems.
AB  - Sewage sludge ash can potentially be used for the removal of metal ions from
      wastewater because its chemical composition is similar to that of fly ash. The
      aim of this work was to investigate the adsorptive characteristics of this
      material, including specific surface area and pH of zero point of charge (pH
      zpc), and to assess the possibility of removing nickel and cadmium from aqueous
      solutions by this sorbent. The effects of agitation time, pH, initial metal ion
      concentration and temperature on the removal of these metals were studied. In
      order to study the sorption isotherm, two equilibrium models, the Langmuir and
      Freundlich isotherms, were analysed. The effect of solution pH on the adsorption
      on to sewage sludge ash was studied in the pH range from 2 to 8. The adsorption
      was endothermic and the computation of the parameters, delta H0, delta S0 and
      delta G0, indicated that the interactions were thermodynamically favourable.
      Experiments with Ni and Cd adsorption measured together showed that Cd severely
      interfered with Ni adsorption to sewage sludge ash and vice versa.

PMID- 19603704
TI  - Anaerobic co-digestion of poultry blood with OFMSW: FTIR and TG-DTG study of
      process stabilization.
AB  - The potential of anaerobic digestion for the treatment of poultry blood has been
      evaluated in a co-digestion process. The organic fraction of municipal solid
      waste (OFMSW) was employed as the co-substrate to avoid digestion inhibition by
      dilution of nitrogen content and improvement of biodegradability. A semi
      continuous mesophilic anaerobic digester was studied with a hydraulic retention
      time (HRT) of 36 days and an organic loading (OLR1) of 1.5 kg VSS feed m(-3) d(
      1). The normal operational conditions of the reactor were altered with the
      application of an OLR2 of 2.0 kg VSS feed m(-3) d(-1) for a short period causing
      an imbalance in the process. The reduction of the OLR to initial conditions
      allowed the recovery of the system. The digestion process reached a final
      specific gas production (SGP) and a methane yield of 0.33 and 0.20 m3 kg(-1) VSS
      feed, respectively, maintaining low total and free ammonia concentrations.
      Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis
      (TGA) were used to gain an insight into transformations experimented by the
      organic matter at the end of the stabilization process. Furthermore, these
      analytical techniques were used for evaluating the transformations undergone by
      the nitrogen-rich protein components of blood after digestion. It was proved that
      a reduction in volatile content and aliphatic structures of biowastes along with
      an increase in the degree of aromaticity occurred during the digestion process.

PMID- 19603705
TI  - Nano-adsorbents for the removal of metallic pollutants from water and wastewater.
AB  - Of the variety of adsorbents available for the removal of heavy and toxic metals,
      activated carbon has been the most popular. A number of minerals, clays and waste
      materials have been regularly used for the removal of metallic pollutants from
      water and industrial effluents. Recently there has been emphasis on the
      application of nanoparticles and nanostructured materials as efficient and viable
      alternatives to activated carbon. Carbon nanotubes also have been proved
      effective alternatives for the removal of metallic pollutants from aqueous
      solutions. Because of their importance from an environmental viewpoint, special
      emphasis has been given to the removal of the metals Cr, Cd, Hg, Zn, As, and Cu.
      Separation of the used nanoparticles from aqueous solutions and the health
      aspects of the separated nanoparticles have also been discussed. A significant
      number of the latest articles have been critically scanned for the present review
      to give a vivid picture of these exotic materials for water remediation.

PMID- 19603706
TI  - Poly(methacrylic acid)-modified sugarcane bagasse for enhanced adsorption of
      cationic dye.
AB  - The preparation of poly(methacrylic acid)-modified sugarcane bagasse (SB) and its
      application for the removal of the cationic dye malachite green (MG) in aqueous
      solution in a batch system is described. The modified SB was characterized using
      SEM and FTIR analysis. The effects of the pH of the solution, contact time and
      initial dye concentration were studied. The adsorption capacity of the adsorbent
      for MG increased significantly after the modification as a large number of
      carboxyl groups were introduced. The equilibrium process was better described by
      the Langmuir than the Freundlich isotherm. According to the Langmuir equation,
      the maximum adsorption capacity was 103.2 mg g(-1) for MG. Kinetic studies showed
      better correlation coefficients for a pseudo-second-order kinetic model,
      confirming that the adsorption rate was controlled by a chemisorption process.

PMID- 19603707
TI  - The effects of a lower irrigation system on pollutant removal and on the
      microflora of a biofilter.
AB  - Moisture control is one the most important parameters in biofilters for air
      pollution control. Biofilters tend to experience drying at the air inlet port,
      which causes decreased pollutant removal over time. In this study, the
      installation of an irrigation system within the lower part of the biofilter bed
      was proposed, and its effect was quantified in a laboratory scale biofilter
      operated side by side with a control biofilter. The removal of toluene vapours at
      short gas residence time (13.5 s) served as a model system. The results showed
      that the rate of toluene elimination in the biofilter with the lower irrigation
      system was 1.2-1.7 times greater than the rate of toluene elimination in the
      control biofilter. At the completion of the two-month experiment, a detailed
      examination was conducted of the packing materials with the immobilized pollutant
      degrading culture. The results highlighted the effects of bed drying on cell
      viability in the control biofilter. They also revealed that the bottom segment of
      the biofilter with the lower irrigation system had a higher moisture content, a
      higher biomass density and a larger fraction of active biomass than the
      corresponding segment in the conventional biofilter. These detailed examinations
      explained why an increased toluene removal was observed in the system equipped
      with a lower irrigation system. Overall, this study demonstrates enhanced
      pollutant removal in biofilters equipped with a lower irrigation system through a
      better control of moisture.

PMID- 19603708
TI  - Microfiltration membrane plant start up: a case study with autopsy and
      permeability recovery analysis.
AB  - A potable water treatment plant, supplied from a low NOM (natural organic
      matter), low turbidity source with precoagulation and two-stage pressure sand
      filtration, had a MF (microfiltration) membrane process added to meet UK Water
      Regulations. An autopsy of the membrane modules showed that despite upstream
      coagulation/filtration with chlorination, a biofilm of EPS (extracellular
      polymeric substances) and inorganic particulates had developed. Backwashing under
      laboratory conditions yielded an almost full recovery. Laboratory-scale modules
      of fouled fibres from pre-commissioning and post-commissioning were assembled and
      cleaned. The recovery was modelled and optimized with a response surface
      experiment using variables of concentration, soak period and temperature. The pre
      commissioning fibres were more recovered by longer chemical soak times at higher
      cleanant concentrations than the post-commissioning fibres. Comparative tests on
      post-commissioning fibres indicated that full recovery was possible with organic
      acids. It was concluded that start-up of new membrane plants may involve fouling
      conditions not necessarily representative of those under routine operating
      conditions, such that modification to prescribed cleaning operations may be
      required.

PMID- 19603709
TI  - We can't wait ... for a health system that works for everyone.

PMID- 19603710
TI  - Maintaining charitable mission in tough times.

PMID- 19603711
TI  - Market-driven health care: can mission survive?

PMID- 19603712
TI  - Administering church goods.

PMID- 19603713
TI  - It's good to be good: science says it's so. Research demonstrates that people who
      help others usually have healthier, happier lives.

PMID- 19603714
TI  - Liturgy has the power to change us. Like a text, it offers an alternate world of
      risk and growth.

PMID- 19603715
TI  - Without love, we perish. Gospel-centered health care is a radical approach in
      today's secular world.

PMID- 19603716
TI  - Theology goes to work. Applying theological reflection to the business of the
      day.

PMID- 19603717
TI  - Sharing expertise on aging across the globe.

PMID- 19603718
TI  - Establishing a national model to aid the homeless.

PMID- 19603719
TI  - 'Thinking green' on behalf of patients and workers.

PMID- 19603720
TI  - Leading the campaign to reduce conflicts of interest.

PMID- 19603721
TI  - Forecasting the future of transformative technologies.

PMID- 19603722
TI  - The day after trinity. Just as nuclear threats continue to influence foreign
      policy, the ghosts of past efforts to improve the U.S. health system still
      trouble us.

PMID- 19603723
TI  - Industry-physician relationships: a call for greater distance. Catholic health
      care systems need to join others in adopting stricter guidelines.

PMID- 19603724
TI  - Leading mothers through their times of sorrow.

PMID- 19603725
TI  - Relying on faith to orchestrate a $27 million turnaround.

PMID- 19603727
TI  - Recession Rx: cut costs for supplies and services. Interview by Alan Joch.

PMID- 19603726
TI  - The human spirit is the most untapped unnatural resource.

PMID- 19603728
TI  - Speeding up infection detection. Hospitals begin to embrace rapid lab tests.

PMID- 19603729
TI  - Is it time to relocate your central storeroom?

PMID- 19603730
TI  - What to do before a new product launch.

PMID- 19603732
TI  - A big turnaround in pump delivery.

PMID- 19603731
TI  - Meeting the challenge of proper hand hygiene.

PMID- 19603733
TI  - Endoscope processing incidents present partnership opportunity.

PMID- 19603734
TI  - Remote sensing of particulate pollution from space: have we reached the promised
      land?
AB  - The recent literature on satellite remote sensing of air quality is reviewed.
      2009 is the 50th anniversary of the first satellite atmospheric observations. For
      the first 40 of those years, atmospheric composition measurements, meteorology,
      and atmospheric structure and dynamics dominated the missions launched. Since
      1995, 42 instruments relevant to air quality measurements have been put into
      orbit. Trace gases such as ozone, nitric oxide, nitrogen dioxide, water,
      oxygen/tetraoxygen, bromine oxide, sulfur dioxide, formaldehyde, glyoxal,
      chlorine dioxide, chlorine monoxide, and nitrate radical have been measured in
      the stratosphere and troposphere in column measurements. Aerosol optical depth
      (AOD) is a focus of this review and a significant body of literature exists that
      shows that ground-level fine particulate matter (PM2.5) can be estimated from
      columnar AOD. Precision of the measurement of AOD is +/-20% and the prediction of
      PM2.5 from AOD is order +/-30% in the most careful studies. The air quality needs
      that can use such predictions are examined. Satellite measurements are important
      to event detection, transport and model prediction, and emission estimation. It
      is suggested that ground-based measurements, models, and satellite measurements
      should be viewed as a system, each component of which is necessary to better
      understand air quality.

PMID- 19603735
TI  - Gaseous oxygen uptake in porous media at different moisture contents and airflow
      velocities.
AB  - The presence and distribution of water in the pore space is a critical factor for
      flow and transport of gases through unsaturated porous media. The water content
      also affects the biological activity necessary for treatment of polluted gas
      streams in biofilters. In this research, microbial activity and quantity of
      inactive volume in a porous medium as a function of moisture content and gas flow
      rate were investigated. Yard waste compost was used as a test medium, and oxygen
      uptake rate measurements were used to quantify microbial activity and effective
      active compost volume using batch and column flow-through systems. Compost water
      contents were varied from air-dry to field capacity and gas flows ranged from 0.2
      to 2 L x min(-1). The results showed that overall microbial activity and the
      relative fraction of active compost medium volume increased with airflow velocity
      for all levels of water content up to a certain flow rate above which the oxygen
      uptake rate assumed a constant value independent of gas flow. The actual value of
      the maximum oxygen uptake rate was controlled by the water content. The oxygen
      uptake rate also increased with increasing water content and reached a maximum
      between 42 and 48% volumetric water content, above which it decreased, again
      likely because of formation of inactive zones in the compost medium. Overall,
      maximum possible oxygen uptake rate as a function of gas flow rate across all
      water contents and gas flows could be approximated by a linear expression. The
      relative fraction of active volume also increased with gas flow rate and reached
      approximately 80% for the highest gas flows used.

PMID- 19603736
TI  - Real-time airflow rate measurements from mechanically ventilated animal
      buildings.
AB  - This paper describes techniques used to determine airflow rate in multiple
      emission point applications typical of animal housing. An accurate measurement of
      building airflow rate is critical to accurate emission rate estimates. Animal
      housing facilities rely almost exclusively on ventilation to control inside
      climate at desired conditions. This strategy results in building airflow rates
      that range from about three fresh-air changes per hour in cold weather to more
      than 100 fresh-air changes per hour in hot weather. Airflow rate measurement
      techniques used in a comprehensive six-state study could be classified in three
      general categories: fan indication methods, fan rotational methods, and airspeed
      measurement methods. Each technique is discussed and implementation plans are
      noted. A detailed error analysis is included that estimated the uncertainty in
      airflow rate between +/-5 and +/-6.1% of reading at a building operating static
      pressure, air temperature, relative humidity, and barometric pressure of 20 Pa,
      25 degrees C, 50%, and 97,700 Pa, respectively.

PMID- 19603738
TI  - Wind tunnel measurements of the dilution of tailpipe emissions downstream of a
      car, a light-duty truck, and a heavy-duty truck tractor head.
AB  - The particle and gaseous pollutants in vehicle exhaust emissions undergo rapid
      dilution with ambient air after exiting the tailpipe. The rate and extent of this
      dilution can greatly affect both the size evolution of primary exhaust particles
      and the potential for formation of ultrafine particles. Dilution ratios were
      measured inside of a wind tunnel in the region immediately downstream of the
      tailpipe using model vehicles (approximately one-fifth to one-seventh scale
      models) representing a light-duty truck, a passenger car, and a heavy-duty
      tractor head (without the trailer). A tracer gas (ethene) was released at a
      measured flow rate from the tailpipe, and 60 sampling probes placed downstream of
      the vehicle simultaneously sampled gas tracer concentrations in the near-wake
      (first few vehicle heights) and far-wake regions (beyond 10 vehicle heights).
      Tests using different tunnel wind speeds show the range of dilution ratios that
      can be expected as a function of vehicle type and downstream distance (i.e.,
      time). The vehicle shape quite strongly influences dilution profiles in the near
      wake region but is much less important in the far-wake region. The tractor
      generally produces higher dilution rates than the automobile and light-duty truck
      under comparable conditions.

PMID- 19603737
TI  - Accuracy of exhaust emission factor measurements on chassis dynamometer.
AB  - To improve the accuracy, reliability, and representativeness of emission factors,
      10 European laboratories worked together to study the influence of 20 parameters
      on the measurement of light-vehicle emission factors on chassis dynamometer of 4
      main categories: driving patterns, vehicle-related parameters, vehicle sampling,
      and laboratory-related parameters. The results are based on (1) literature
      synthesis, (2) approximately 2700 specific tests with 183 vehicles, and (3) the
      reprocessing of more than 900 tests. These tests concern the regulated
      atmospheric pollutants and pre-Euro to Euro 4 vehicles. Of the 20 parameters
      analyzed, 7 seemed to have no effect, 7 were qualitatively influential, and 6
      were highly influential (gearshift strategy, vehicle mileage, ambient
      temperature, humidity, dilution ratio, and driving cycle). The first four of the
      six were able to have correction factors developed for them. The results allow
      for the design of recommendations or guidelines for the emission factor
      measurement method.

PMID- 19603739
TI  - Dilution rates for tailpipe emissions: effects of vehicle shape, tailpipe
      position, and exhaust velocity.
AB  - The rate at which motor vehicle exhaust undergoes dilution with ambient air will
      greatly affect the size distribution characteristics of the particulate
      emissions. Wind tunnel experiments were conducted to investigate the impacts of
      vehicle shape, tailpipe orientation, and exhaust exit velocity on the dilution
      profiles under steady driving conditions for three model vehicles: a light-duty
      truck, a passenger car, and a heavy-duty tractor head. A three dimensional array
      of 60 sensors provided simultaneous measurements of dilution ratios for the
      emissions in the near- and far-wake regions downstream of the vehicle. The
      processes underlying the observations were investigated via
      nondimensionalization. Many of the trends seen substantially downstream can be
      well generalized using a simple nondimensionalization technique; however, this is
      not true in the near-wake region (within a downstream distance equivalent to a
      few vehicle heights). In the near-wake region, using the vehicle width and length
      to normalize for the vehicle shape is not enough to fully account for the
      variations seen. Including the exhaust flow rate in the nondimensionalization
      process is effective further downwind but does not adequately capture the
      complexity in the near-wake region. Tailpipe orientation and location are also
      shown to be influential factors affecting the near-wake dilution characteristics.

PMID- 19603740
TI  - Potential flue gas impurities in carbon dioxide streams separated from coal-fired
      power plants.
AB  - For geological sequestration of carbon dioxide (CO2) separated from pulverized
      coal combustion flue gas, it is necessary to adequately evaluate the potential
      impacts of flue gas impurities on groundwater aquifers in the case of the CO2
      leakage from its storage sites. This study estimated the flue gas impurities to
      be included in the CO2 stream separated from a CO2 control unit for a different
      combination of air pollution control devices and different flue gas compositions.
      Specifically, the levels of acid gases and mercury vapor were estimated for the
      monoethanolamine (MEA)-based absorption process on the basis of published
      performance parameters of existing systems. Among the flue gas constituents
      considered, sulfur dioxide (SO2) is known to have the most adverse impact on MEA
      absorption. When a flue gas contains 3000 parts per million by volume (ppmv) SO2
      and a wet flue gas desulfurization system achieves its 95% removal, approximately
      2400 parts per million by weight (ppmw) SO2 could be included in the separated
      CO2 stream. In addition, the estimated concentration level was reduced to as low
      as 135 ppmw for the SO2 of less than 10 ppmv in the flue gas entering the MEA
      unit. Furthermore, heat-stable salt formation could further reduce the SO2
      concentration below 40 ppmw in the separated CO2 stream. In this study, it is
      realized that the formation rates of heat-stable salts in MEA solution are not
      readily available in the literature and are critical to estimating the levels and
      compositions of flue gas impurities in sequestered CO2 streams. In addition to
      SO2, mercury, and other impurities in separated CO2 streams could vary depending
      on pollutant removal at the power plants and impose potential impacts on
      groundwater. Such a variation and related process control in the upstream
      management of carbon separation have implications for groundwater protection at
      carbon sequestration sites and warrant necessary considerations in overall
      sequestration planning, engineering, and management.

PMID- 19603741
TI  - Modeling of personal exposures to ambient air toxics in Camden, New Jersey: an
      evaluation study.
AB  - This study presents the Individual Based Exposure Modeling (IBEM) application of
      MENTOR (Modeling ENvironment for TOtal Risk studies) in a hot spot area, where
      there are concentrated local sources on the scale of tens to hundreds of meters,
      and an urban reference area in Camden, NJ, to characterize the ambient
      concentrations and personal exposures to benzene and toluene from local ambient
      sources. The emission-based ambient concentrations in the two neighborhoods were
      first estimated through atmospheric dispersion modeling. Subsequently, the
      calculated and measured ambient concentrations of benzene and toluene were
      separately combined with the time-activity diaries completed by the subjects as
      inputs to MENTOR/IBEM for estimating personal exposures resulting from ambient
      sources. The modeling results were then compared with the actual personal
      measurements collected from over 100 individuals in the field study to identify
      the gaps in modeling personal exposures in a hot spot. The modeled ambient
      concentrations of benzene and toluene were generally in agreement with the
      neighborhood measurements within a factor of 2, but were underestimated at the
      high-end percentiles. The major local contributors to the benzene ambient levels
      are from mobile sources, whereas mobile and stationary (point and area) sources
      contribute to the toluene ambient levels in the study area. This finding can be
      used as guidance for developing better air toxic emission inventories for
      characterizing, through modeling, the ambient concentrations of air toxics in the
      study area. The estimated percentage contributions of personal exposures from
      ambient sources were generally higher in the hot spot area than the urban
      reference area in Camden, NJ, for benzene and toluene. This finding demonstrates
      the hot spot characteristics of stronger local ambient source impacts on personal
      exposures. Non-ambient sources were also found as significant contributors to
      personal exposures to benzene and toluene for the population studied.

PMID- 19603742
TI  - Low-energy and chemical-free activation of pyrolytic tire char and its adsorption
      characteristics.
AB  - It is generally known that the solid char obtained from pyrolysis of scrap rubber
      tires can be used as an adsorbent for several applications such as wastewater
      treatment. In this study, scrap tires were first pyrolyzed under nitrogen (N2) or
      carbon dioxide (CO2) gas under various temperatures to produce char. The char was
      activated in situ by post-pyrolysis oxygenation (PPO) at different temperature
      ranges as soon as the pyrolysis process was completed. Elemental and
      spectroscopic analyses showed significant zinc content in the char after PPO.
      Batch-mode removal of aqueous copper (Cu) using the chars revealed that, for N2
      and CO2, the optimum condition for pyrolysis was at 550 degrees C and for
      activation was from 550 to 250 degrees C. Although CO2-pyrolyzed char had lower
      Cu and lead (Pb) removal than N2-pyrolyzed char, it had higher char yields. For
      both N2- and CO2-pyrolyzed char, activation with PPO improved their heavy metal
      removal efficiencies significantly compared with unactivated char. PPO chars had
      much faster removal rates and higher Cu removal compared with both pyrolyzed,
      unactivated char and commercial activated carbons.

PMID- 19603743
TI  - Analysis of motorcycle exhaust regular testing data--a case study of Taipei City.
AB  - In Taiwan, a continuous increase in the number of motorcycles has made exhaust
      pollution one of the major emission sources of air pollutants. The regular
      testing program carried out by the Republic of China Environmental Protection
      Agency was designed to reduce air pollutant emissions by enhancing maintenance
      and repair. During the execution period, abundant testing results were
      accumulated to discuss pollutant emissions from motorcycles. Exhaust testing data
      of motorcycles in Taipei City from 1996 to 2005 were chosen as the basic data to
      survey changes in motorcycle exhaust. Effects of motorcycle age and mileage on
      exhaust pollution were studied. The introduction of advanced emission standards
      enhances the elimination of high-emitting motorcycles. The testing data indicate
      that the testing rate rose from approximately 50 to 70% and the failure rate
      changed from approximately 15 to 10%. The operation cycles of two-stroke
      motorcycles make them high-emitting vehicles. Concentrations of carbon monoxide
      and hydrocarbons are higher in two-stroke motorcycle exhaust than that in four
      stroke motorcycles. In contrast, the concentration of carbon dioxide produced
      from complete oxidation processes is lower in exhaust from two-stroke
      motorcycles. Therefore, failure rates of two-stroke motorcycles are higher than
      those of four-stroke motorcycles and were also observed to deactivate more
      easily. On the basis of analytical results of testing data, we found that failure
      rates show a gradually increasing trend for motorcycles older than 3 yr or used
      for mileages greater than 10,000 km, and failure rates are highly correlated to
      the age/mileage of motorcycles. We reason that the accumulation of age or mileage
      means accumulating usage time of engines and emission control systems.
      Concentrations of pollutant emissions would increase because of engine wear and
      emission control system deactivation. After discussing changes of failure rates
      and pollutant emissions, some suggestions are proposed to improve the testing
      rate and effectiveness of regular testing.

PMID- 19603744
TI  - X-ray photoelectron spectroscopy- and surface plasmon resonance-detected photo
      release of photolabile protecting groups from nucleoside self-assembled
      monolayers on gold surfaces.
AB  - The formation of self-assembled monolayers (SAMs) on gold by 2-(5-iodo-2
      nitrophenyl) propoxycarbonyl (I-NPPOC)-protected thymidine with an attached
      mercaptohexyl succinate linker and the kinetics of photochemical release of the I
      NPPOC group were monitored using X-ray photoelectron spectroscopy (XPS) and
      surface plasmon resonance (SPR) detection. In the XPS spectra, the iodine peaks
      allowed for specific and accurate monitoring of the presence and loss of I-NPPOC
      groups on the surface. In the SPR experiment, the overall signal change on
      photoillumination is in accord with a theoretical estimation of the density of I
      NPPOC groups in a dense monolayer. The kinetics roughly follow a biexponential
      time dependence with two very different time constants, corresponding to
      photochemical quantum yields of 0.22 and 0.0032, respectively.

PMID- 19603747
TI  - gem-Dichlorocyclopropanes as abundant and efficient mechanophores in
      polybutadiene copolymers under mechanical stress.
AB  - When gem-dichlorocyclopropane (gDCC) copolymers derived from polybutadiene are
      subjected to ultrasonication, the gDCCs undergo ring opening to form 2,3
      dichloroalkenes. The reactivity is not observed in low-molecular-weight (6.5 kDa)
      copolymers or side-chain gDCCs, consistent with mechanically induced reactivity
      due to the elongational strain of the polymers in the sonication flow fields. The
      ring openings occur several hundred times more frequently than polymer chain
      scission, and cis-coupled gDCCs are slightly more likely to react than their
      trans isomers. The ability to dramatically and specifically alter the structure
      of the polymer backbone through a coupled restoring force suggests new routes to
      postsynthetic polymer modification and motivates the design of easily scalable
      mechanophores for applications in stress-responsive polymers.

PMID- 19603745
TI  - A mechanism for incorporation of galectin-3 into the spliceosome through its
      association with U1 snRNP.
AB  - Previously, we showed that galectin-1 and galectin-3 are redundant pre-mRNA
      splicing factors associated with the spliceosome throughout the splicing pathway.
      Here we present evidence for the association of galectin-3 with snRNPs outside of
      the spliceosome (i.e., in the absence of pre-mRNA splicing substrate).
      Immunoprecipitation of HeLa nuclear extract with anti-galectin-3 resulted in the
      coprecipitation of the five spliceosomal snRNAs, core Sm polypeptides, and the U1
      specific protein, U1 70K. When nuclear extract was fractionated on glycerol
      gradients, some galectin-3 molecules cosedimented with snRNP complexes. This
      cosedimentation represents bona fide galectin-3--snRNP complexes as (i)
      immunoprecipitation of gradient fractions with anti-galectin-3 yielded several
      complexes with varying ratios of snRNAs and associated proteins and (ii) the
      distribution of galectin-3--snRNP complexes was altered when the glycerol
      gradient was sedimented in the presence of lactose, a galectin ligand. A complex
      at approximately 10S showed an association of galectin-3 with U1 snRNP that was
      sensitive to treatment with ribonuclease A. We tested the ability of this U1
      snRNP to recognize an exogenous pre-mRNA substrate. Under conditions that
      assemble early splicing complexes, we found this isolated galectin-3--U1 snRNP
      particle was sufficient to load galectin-3 onto a pre-mRNA substrate, but not
      onto a control RNA lacking splice sites. Pretreatment of the U1 snRNP with
      micrococcal nuclease abolished the assembly of galectin-3 onto this early
      complex. These data identify galectin-3 as a polypeptide associated with snRNPs
      in the absence of splicing substrate and describe a mechanism for the assembly of
      galectin-3 onto the forming spliceosome.

PMID- 19603746
TI  - Pyridinium ylide-assisted one-pot two-step tandem synthesis of polysubstituted
      cyclopropanes.
AB  - A sequential one-pot two-step tandem reaction for efficient synthesis of
      polysubstituted cyclopropanes has been developed. The three-component reaction of
      alpha-halogenated methylene compounds, aromatic aldehydes, and acetonitrile
      derivatives produced first the intermediates pyridinium salts and electron
      deficient olefins, followed by cyclopropanation of pyridinium ylide with electron
      deficient olefins in situ to afford polysubstituted cyclopropanes. Target
      compounds were obtained in high yields and were diastereomerically pure after
      recrystallization.

PMID- 19603748
TI  - Synthesis and structure of PNP-supported iridium silyl and silylene complexes:
      catalytic hydrosilation of alkenes.
AB  - Oxidative addition of bulky primary, secondary, and tertiary silanes to PNP (PNP
      = [N(2-P(i)Pr(2)-4-Me-C(6)H(3))(2)](-)) iridium complexes (PNP)IrH(2) and
      (PNP)Ir(COE) (11) afforded iridium silyl hydride complexes (PNP)Ir(H)(SiRR'R'')
      (3-8). Addition of 2 equiv of PhSiH(3) or (3,5-Me(2)C(6)H(3))SiH(3) to
      (PNP)IrH(2) or 11 yielded disilyl complexes (PNP)Ir(SiH(2)R)(2) (R = Ph (9), 3,5
      Me(2)C(6)H(3) (10)). Hydride abstraction from (PNP)Ir(H)(SiH(2)R) (R = Trip (5),
      Dmp (6)) by [Ph(3)C][B(C(6)F(5))(4)] afforded iridium silylene complexes
      [(PNP)(H)Ir=SiR(H)][B(C(6)F(5))(4)] (R = Trip (12), Dmp (13)) exhibiting
      downfield (29)Si NMR resonances (234 ppm (12), 226 ppm (13)) and downfield (1)H
      NMR resonances for the Si-H group (10.76 ppm (12), 9.76 ppm (13)). Thermally
      stable disubstituted silylene complexes [(PNP)(H)Ir=SiPh(2)][A] (A = (
      )B(C(6)F(5))(4) (14), (-)CB(11)H(6)Br(6) (16)) were isolated via hydride
      abstraction from (PNP)Ir(H)(SiHPh(2)). The X-ray structure of 16 confirmed sp(2)
      hybridization at silicon and revealed a short Ir-Si bond of 2.210(2) A. Catalytic
      hydrosilation of alkenes by hydrogen-substituted silylene complexes
      [(PNP)(H)Ir=SiMes(H)][B(C(6)F(5))(4)] (1) and 14 exhibited anti-Markovnikov
      regioselectivity with an array of alkene substrates. Addition of H(3)SiMes to
      complex 1 afforded [(PNP)(SiH(Mes)(Hex))IrH(SiH(2)Mes)][B(C(6)F(5))(4)] (19),
      featuring a beta-agostic interaction demonstrated by a J(SiH) of 102 Hz for the N
      SiH hydrogen. Similarly, addition of H(2)SiPh(2) to 16 afforded the structurally
      characterized Ir(V) disilyl complex
      [(PNP)(SiPh(2))Ir(SiPh(2)H)(H)(2)][CB(11)H(6)Br(6)] (20). Complex 20 was found to
      be catalytically active for the hydrosilation of alkenes, which is consistent
      with its intermediacy in the catalytic cycle.

PMID- 19603749
TI  - Effect of high-oxygen atmospheres on the antioxidant potential of fresh-cut
      tomatoes.
AB  - The effect of different initial in-package O2 and CO2 concentrations (2.5 kPa of
      O2 + 5 kPa of CO2, 10 kPa of O2 + 5 kPa of CO2, and 21, 60, and 80 kPa of O2) on
      the antioxidant potential of fresh-cut tomatoes was investigated. Changes in
      individual phenolic compounds, individual carotenoids, vitamin C, and antioxidant
      capacity as well as in O2, CO2, and ethylene headspace concentrations inside
      packages were assessed for 21 days at 4 degrees C. High-oxygen and passive
      atmospheres induced higher production of carotenoids and phenolic compounds. The
      degradation of the initial content of vitamin C was highly promoted by the
      presence of oxygen. Lower hydrophilic antioxidant capacity (DPPH assay) was
      obtained in tomato slices stored under 80 kPa of O2, whereas the antioxidant
      capacity of the lipophilic fraction was enhanced with oxygen availability inside
      headspace packages. Therefore, 2.5 kPa of O2 + 5 kPa of CO2 atmospheres not only
      reduced the formation of carotenoids but also maintained vitamin C in fresh-cut
      tomatoes.

PMID- 19603750
TI  - Stereoisomeric separation and bioassay of a new organophosphorus compound, O,S
      dimethyl-N-(2,2,2-trichloro-1-methoxyethyl)phosphoramidothioate: some
      implications for chiral switch.
AB  - The manufacture and use of single- or enriched-enantiomer pesticides are green
      chemistry developments advocated in the 21st century, but predictive work for
      chiral switch of newly produced chiral active ingredients is limited. In the
      present study, the stereoselective separation, target activity, and nontarget
      toxicity of O,S-dimethyl-N-(2,2,2-trichloro-1-methoxyethyl)phosphoramidothioate
      (MCP), a new organophosphorus compound, were investigated. Because being highly
      active and safe is a prerequisite for marketing single-isomer products, the above
      studies were used to offer some implications for the chiral switch of racemic
      MCP. The results showed that all four stereoisomers of MCP were successfully
      separated with a Chiralpak AD column on HPLC. The resolved isomers and the pairs
      of enantiomers were further distinguished using a circular dichroism detector,
      designating the first and third eluted peaks as one pair of enantiomers and the
      second and fourth peaks as the other pair. Then, the insecticidal activities and
      acute and delayed toxicities of the resolved isomers of MCP were evaluated by
      their acute lethal efficacy against Daphina magna , their inhibitory potentials
      to acetylcholinesterase (AChE), and axon-like outgrowth of the SH-SY5Y cells,
      respectively. The inhibition potencies of the isomers against AChE in SH-SY5Y
      cells were low and slightly stereoselective. On the other hand, a significant
      difference was observed among the isomers in their activities and delayed
      neurotoxicities. The 48 h acute toxicities of isomers to D. magna followed the
      order peak 1 approximately pair 1 (i.e., equimolar mixture of peaks 1 and 3) >
      peak 4 approximately racemate > pair 2 (i.e., equimolar mixture of peaks 2 and 4)
      > peak 2 > peak 3, with 1.0-6.3-fold differences among them. In comparison, the
      inhibitory potentials of the isomers toward axon growth of SH-SY5Y cells
      decreased in the order peak 2 > pair 2 > peak 4 > racemate > peak 3 > pair 1
      approximately peak 1, with at least a 60-fold difference between the strongest
      and weakest inhibitors. Those results imply that peak 1 has the optimal target
      selectivity and ecological profile among the four stereoisomers. It was
      calculated that two-thirds of the usual pesticide usage can be saved
      concomitantly with a substantial decrease in neuropathic risk if MCP is present
      only as peak 1 rather than the racemate. When considering the absence of the
      economically feasible synthetic methods and techniques to produce optically pure
      isomers of organophosphorus pesticides, pair 1 of MCP shows considerable worth
      for future applications on the basis of its biological predominance and cost
      effectiveness.

PMID- 19603751
TI  - Stereoselective synthesis of (+)-aspidofractinine.
AB  - We describe the synthesis of (+)-aspidofractinine, the enantiomer of a naturally
      occurring alkaloid of the kopsane family. Key features of the synthesis include a
      stereospecific cyanate to isocyanate rearrangement on a chiral scaffold, a ring
      closing alkene metathesis to cleave the chiral auxiliary, and a chemoselective
      cyclopropanation to introduce the quaternary carbon at position 7 of
      aspidofractinine.

PMID- 19603753
TI  - A general copper-catalyzed coupling of azoles with vinyl bromides.
AB  - A copper-catalyzed methodology for the coupling of vinyl bromides with azoles has
      been developed. This protocol uses a combination of 10 mol % of copper iodide and
      20 mol % of ethylenediamine as catalyst. The reaction proceeds with various
      azoles and vinyl bromides, and the double bond geometry of vinyl bromides is
      retained under the reaction conditions.

PMID- 19603755
TI  - Nanoscale heterogeneous structure of ionic liquid as revealed by magnetic field
      effects.
AB  - Large magnetic field effects (MFEs) observed for photoinduced hydrogen
      abstraction reaction between benzophenone and thiophenol in an ionic liquid
      (N,N,N,-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)amide, TMPA TFSA)
      are analyzed by using the stochastic Liouville equation for the first time. The
      sphere cage model can well reproduce the observed MFEs and the nanoscale
      heterogeneous structure with a cage radius of 1.8 +/- 0.3 nm, and an effective
      viscosity in the cage of 1-2 cP is found to be formed in TMPA TFSA.

PMID- 19603752
TI  - Charge density-dependent modifications of hydration shell waters by Hofmeister
      ions.
AB  - Gadolinium (Gd(3+)) vibronic sideband luminescence spectroscopy (GVSBLS) is used
      to probe, as a function of added Hofmeister series salts, changes in the OH
      stretching frequency derived from first-shell waters of aqueous Gd(3+) and of
      Gd(3+) coordinated to three different types of molecules: (i) a chelate (EDTA),
      (ii) structured peptides (mSE3/SE2) of the lanthanide-binding tags (LBTs) family
      with a single high-affinity binding site, and (iii) a calcium-binding protein
      (calmodulin) with four binding sites. The vibronic sideband (VSB) corresponding
      to the OH stretching mode of waters coordinated to Gd(3+), whose frequency is
      inversely correlated with the strength of the hydrogen bonding to neighboring
      waters, exhibits an increase in frequency when Gd(3+) becomes coordinated to
      either EDTA, calmodulin, or mSE3 peptide. In all of these cases, the addition of
      cation chloride or acetate salts to the solution increases the frequency of the
      vibronic band originating from the OH stretching mode of the coordinated waters
      in a cation- and concentration-dependent fashion. The cation dependence of the
      frequency increase scales with charge density of the cations, giving rise to an
      ordering consistent with the Hofmeister ordering. On the other hand, water Raman
      spectroscopy shows no significant change upon addition of these salts.
      Additionally, it is shown that the cation effect is modulated by the specific
      anion used. The results indicate a mechanism of action for Hofmeister series ions
      in which hydrogen bonding among hydration shell waters is modulated by several
      factors. High charge density cations sequester waters in a configuration that
      precludes strong hydrogen bonding to neighboring waters. Under such conditions,
      anion effects emerge as anions compete for hydrogen-bonding sites with the
      remaining free waters on the surface of the hydration shell. The magnitude of the
      anion effect is both cation and Gd(3+)-binding site specific.

PMID- 19603754
TI  - Similar energetic contributions of packing in the core of membrane and water
      soluble proteins.
AB  - A major driving force for water-soluble protein folding is the hydrophobic
      effect, but membrane proteins cannot make use of this stabilizing contribution in
      the apolar core of the bilayer. It has been proposed that membrane proteins
      compensate by packing more efficiently. We therefore investigated packing
      contributions experimentally by observing the energetic and structural
      consequences of cavity creating mutations in the core of a membrane protein. We
      observed little difference in the packing energetics of water and membrane
      soluble proteins. Our results imply that other mechanisms are employed to
      stabilize the structure of membrane proteins.

PMID- 19603756
TI  - First-principles thermochemistry for silicon species in the decomposition of
      tetraethoxysilane.
AB  - Tetraethoxysilane (TEOS) is used as a precursor in the industrial production of
      silica nanoparticles using thermal decomposition methods such as flame spray
      pyrolysis (FSP). Despite the industrial importance of this process, the current
      kinetic model of high-temperature decomposition of TEOS to produce intermediate
      silicon species and eventually form amorphous silica (R-SiO2) nanoparticles
      remains inadequate. This is partly due to the fact only a small proportion of the
      possible species is considered. This work presents the thermochemistry of
      practically all of the species that can exist in the early stages of the reaction
      mechanism. In order to ensure that all possible species are considered, the
      process is automated by considering all species that can be formed from the
      reactions that are deemed reasonable in the standard ethanol combustion model in
      the literature. Thermochemical data for 180 species (over 160 of which have not
      appeared in the literature before) are calculated using density functional theory
      with two different hybrid functionals, B3LYP and B97-1. The standard enthalpy of
      formation (DeltafH(298.15K) degrees) values for these species are calculated
      using isodesmic reactions. It is observed that internal rotation may be important
      because the barriers to rotation are reasonably low. Comparisons are then made
      between the rigid rotor harmonic oscillator approximation (RRHO) and the RRHO
      with some of the vibrational modes treated as hindered rotors. It is found that
      full treatment of the hindered rotors makes a significant difference to the
      thermochemistry and thus has an impact on equilibrium concentrations and kinetics
      in this system. For this reason, all of the species are treated using the
      hindered rotor approximation where appropriate. Finally, equilibrium calculations
      are performed to identify the intermediates that are likely to be most prevalent
      in the high-temperature industrial process. Particularly, Si(OH)4, SiH(OH)3,
      SiH2(OH)2, SiH3(OH), Si(OH)3(OCH3), Si(OH)2(OCH3)2, the silicon dimers (CH3)3
      SiOSi(CH3)3 and SiH3OSiH3, and the smaller hydrocarbon species CH4, CO2, C2H4,
      and C2H6 are highlighted as the important species.

PMID- 19603757
TI  - Reduction of oxyiron(V) by sulfite and thiosulfate in aqueous solution.
AB  - The reduction of oxyiron(V), Fe(V)O(4)(3-) by inorganic oxysulfur species
      (SO(3)(2-) and S2O(3)(2-)) has been studied anaerobically in alkaline medium by
      using a premix pulse radiolysis technique. Studies on the reactions of
      Fe(VI)O(4)(2-) with the two sulfur radicals were also carried out. The
      spectroscopic results demonstrated that sulfur radicals reduced Fe(VI)O(4)(2-) to
      Fe(V)O(4)(3-) which is subsequently reduced by oxysulfur species by a two
      electron reduction step to Fe(III). The rate constants for reduction of
      Fe(VI)O(4)(2-) to Fe(V)O(4)(3-) by sulfite and thiosulfate radicals (*SO3- and
      S4O(6)(*3-)) were found to be (1.9 +/- 0.3) x 10(8) and (7.5 +/- 0.8) x 10(7) M(
      1) s(-1), respectively. However, the reactions of Fe(V)O(4)(3-) with the SO(3)(2
      ) and S2O(3)(2-) ions were separated by an order of magnitude, with SO(3)(2-)
      reacting at (3.9 +/- 0.3) x 10(4) M(-1) s(-1) while S2O(3)(2-) reacted with Fe(V)
      at (2.1 +/- 0.1) x 10(3) M(-1) s(-1) at pH 11.4.

PMID- 19603758
TI  - Structural evolution of the [(CO2)n(H2O)]- cluster anions: quantifying the effect
      of hydration on the excess charge accommodation motif.
AB  - The [(CO2)n(H2O)]- cluster anions are studied using infrared photodissociation
      (IPD) spectroscopy in the 2800-3800 cm(-1) range. The observed IPD spectra
      display a drastic change in the vibrational band features at n = 4, indicating a
      sharp discontinuity in the structural evolution of the monohydrated cluster
      anions. The n = 2 and 3 spectra are composed of a series of sharp bands around
      3600 cm(-1), which are assignable to the stretching vibrations of H2O bound to
      C2O4- in a double ionic hydrogen-bonding (DIHB) configuration, as was previously
      discussed (J. Chem. Phys. 2005, 122, 094303). In the n > or = 4 spectrum, a pair
      of intense bands additionally appears at approximately 3300 cm(-1). With the aid
      of ab initio calculations at the MP2/6-31+G* level, the 3300 cm(-1) bands are
      assigned to the bending overtone and the hydrogen-bonded OH vibration of H2O
      bound to CO2- via a single O-H...O linkage. Thus, the structures of [(CO2)n(H2O)]
      evolve with cluster size such that DIHB to C2O4- is favored in the smaller
      clusters with n = 2 and 3 whereas CO2- is preferentially stabilized via the
      formation of a single ionic hydrogen-bonding (SIHB) configuration in the larger
      clusters with n > or = 4.

PMID- 19603759
TI  - State-to-state vibrational energy transfer in OH A2Sigma+ with N2.
AB  - Vibrational energy transfer from v' = 0 to v' = 1 in the excited OH A2Sigma+
      electronic state is investigated in the collisional region of a free-jet
      expansion. Laser excitation is used to prepare high rotational levels in OH
      A2Sigma+ (v' = 0, N' = 14-22), which lie above the energetic threshold for OH
      A2Sigma+ (v' = 1). Subsequent collisions with N2 result in population of a
      distribution of OH A2Sigma+ (v' = 1) product rotational levels that is
      characterized through dispersed fluorescence spectra. The majority of products
      are found in the most near-resonant rotational level of v' = 1, with population
      falling off exponentially in lower rotational levels. Additionally, the
      efficiency of vibrational energy transfer is determined by comparing the emission
      from v' = 1 products with that from the initially prepared v' = 0 level. The
      fractional transfer decreases by an order of magnitude from the highest to lowest
      initial rotational levels investigated. This decrease is correlated with an
      increasingly large change in rotational angular momentum between the initial and
      final states. The results show that angular momentum constraints are the dominant
      factor in the efficiency of OH A2Sigma+ v' = 0 to v' = 1 vibrational energy
      transfer at low collision energies.

PMID- 19603760
TI  - Thiolated gold nanowires: metallic versus semiconducting.
AB  - Tremendous research efforts have been spent on thiolated gold nanoparticles and
      self-assembled monolayers of thiolate (RS-) on gold, but thiolated gold nanowires
      have received almost no attention. Here we computationally design two such one
      dimensional nanosystems by creating a linear chain of Au icosahedra, fused
      together by either vertex sharing or face sharing. Then neighboring Au icosahedra
      are bridged by five thiolate groups for the vertex-sharing model and three RS-Au
      SR motifs for the face-sharing model. We show that the vertex-sharing thiolated
      gold nanowire can be made either semiconducting or metallic by tuning the charge,
      while the face-sharing one is always metallic. We explain this difference between
      the two nanowires by examining their band structures and invoking a previously
      proposed electron-count rule. Implications of our findings for previous
      experimentation of gold nanowires are discussed, and a potential way to make
      thiolated gold nanowires is proposed.

PMID- 19603761
TI  - SmI2-promoted intramolecular asymmetric pinacol-type ketone-tert-butanesulfinyl
      imine reductive coupling: stereoselectivity and mechanism.
AB  - The asymmetric ketone-tert-butanesulfinyl (t-BS) imine pinacol-type reductive
      coupling promoted by SmI(2) is described. Trans-1,2-vicinal amino alcohols were
      formed predominantly in excellent er and high dr. The stereochemical outcome
      provided evidence for a radical mechanism for SmI(2)-induced reductive couplings
      of t-BS imines.

PMID- 19603763
TI  - NMR studies of structure and dynamics of liquid molecules confined in extended
      nanospaces.
AB  - We fabricated an NMR cell equipped with 10-100 nm scale spaces on a glass
      substrate (called extended nanospaces), and investigated molecular structure and
      dynamics of water confined in the extended nanospaces by (1)H NMR chemical shift
      (delta(H)) and (1)H and (2)H NMR spin-lattice relaxation rate ((1)H- and (2)H
      1/T(1)), (1)H NMR spin-spin relaxation rate ((1)H-1/T(2)), and (1)H NMR rotating
      frame spin-lattice relaxation rate ((1)H-1/T(1rho)) measurements of H(2)O and
      (2)H(2)O. The delta(H) and (1)H- and (2)H-1/T(1) results showed that size
      confinement produces slower translational motions and higher proton mobility of
      water, but does not affect the hydrogen-bonding structure and rotational motions.
      Such unique phenomena appeared in the space size of 40 to 800 nm. However, the
      (1)H-1/T(1) value at 40 nm was still different from that in 4 nm porous
      nanomaterial, because translational and rotational motions were inhibited for
      H(2)O molecules in the nanomaterial. By examining temperature- and deuterium
      dependence of the (1)H-1/T(1) values, the molecular translational motions of the
      confined water were found to be controlled by protonic diffusion invoking a
      proton hopping pathway between adjacent water rather than hydrodynamic
      translational diffusion. Furthermore, we clarified that proton exchange between
      adjacent water molecules in extended nanospaces could be enhanced by the chemical
      exchange of protons between water and SiOH groups on glass surfaces, ( identical
      with SiO(-)...H(+)...H(2)O) + H(2)O --> triple bond SiO(-) + (H(3)O(+) + H(2)O) -
      > triple bond SiO(-) + (H(2)O + H(3)O(+)), based on (1)H-1/T(2) measurements. An
      enhancement of proton exchange rate of water due to the reduction of space sizes
      was verified from the results of (1)H-1/T(1rho) values, and the rate of water in
      the 100 nm sized spaces is larger by a factor of more than ten from that of bulk
      water. Such size-confinement effects were distinctly observed for hydrogen-bond
      solvents with strong proton-donating ability, while they did not appear for
      aprotic and nonpolar solvent cases. Based on these NMR results, we suggested that
      an intermediate phase, in which protons migrate through a hydrogen-bonding
      network and the water molecules are loosely coupled within 50 nm from the
      surface, exists mainly in extended nanospaces. This model could be supported by a
      three-phase theory based on the weight average of three phases invoking the bulk,
      adsorbed, and intermediate phases.

PMID- 19603764
TI  - Host-guest chemistry of dendrimer-drug complexes. 2. Effects of molecular
      properties of guests and surface functionalities of dendrimers.
AB  - The host-guest chemistry of dendrimer-drug complexes is investigated by NMR
      techniques, including (1)H NMR and 2D-NOESY studies. The effects of molecular
      properties of drug molecules (protonation ability and spatial steric hindrance of
      charged groups) and surface functionalities of dendrimers (positively charged
      amine groups and negatively charged carboxylate groups) on the host-guest
      interactions are discussed. Different interaction mechanisms between dendrimers
      and drug molecules are proposed on the basis of NMR results. Primary amine- and
      secondary amine-containing drugs preferentially bind to negatively charged
      dendrimers by strong electrostatic interactions, whereas tertiary amine and
      quaternary ammonium-containing drugs have weak binding ability with dendrimers
      due to relatively low protonation ability of the tertiary amine group and serious
      steric hindrance of the quaternary ammonium group. Positively charged drugs
      locate only on the surface of negatively charged dendrimers, whereas negatively
      charged drugs locate both on the surface and in the interior cavities of
      positively charged dendrimers. The host-guest chemistry of dendrimer-drug
      complexes is promising for the development of new drug delivery systems.

PMID- 19603765
TI  - Gold-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3
      ols. A concise synthesis of (+/-)-angustureine.
AB  - An efficient synthetic route to 1,2-dihydroquinolines that relies on
      AuCl(3)/AgSbF(6)-catalyzed intramolecular allylic amination of 2
      tosylaminophenylprop-1-en-3-ols is described herein. Uniquely, the reactions were
      found to only proceed rapidly at room temperature in the presence of the gold and
      silver catalyst combination and produce the 1,2-dihydroquinoline products in
      yields of 40-91%. The method was shown to be applicable to a broad range of 2
      tosylaminophenylprop-1-en-3-ols containing electron-withdrawing, electron
      donating, and sterically demanding substrate combinations. The mechanism is
      suggested to involve activation of the alcohol substrate by the AuCl(3)/AgSbF(6)
      catalyst. This is followed by ionization of the starting material, which causes
      intramolecular nucleophilic addition of the sulfonamide unit to the allylic
      cation moiety and construction of the 1,2-dihydroquinoline. The utility of this N
      heterocyclic ring forming strategy as a synthetic tool that makes use of alcohols
      as pro-electrophiles was exemplified by its application to the synthesis of the
      bioactive tetrahydroquinoline alkaloid (+/-)-angustureine.

PMID- 19603766
TI  - Interaction potentials, spectroscopy, and transport properties of the Br+-RG
      systems (RG = He-Ar).
AB  - The potential energy curves of Br cations interacting with rare gas (RG = He-Ar)
      atoms are calculated employing the RCCSD(T) technique for the non-spin-orbit
      states, with spin-orbit coupling being included analytically, using an atoms-in
      molecule approach. The curves are calculated employing large basis sets
      extrapolated to the complete basis set limit, and the energies are corrected for
      basis set superposition error. Comparison is made to the limited potentials
      available previously. Gaseous ion mobilities are obtained using the potential
      energy curves of the states of the complex that correlate to the
      Br(+)((3)P(J)(o)) + RG asymptotes. Excellent agreement is obtained with the
      experimental data in He; however, the experimental error bars are such that we
      are unable to determine which spin-orbit state(s) are present in the mobility
      measurements. Finally, a high-resolution photoelectron spectrum is simulated for
      the ionization of Br-Ar.

PMID- 19603768
TI  - Effects of Cr3+ on the structure of collagen fiber.
AB  - We have investigated the effects of Cr3+ on the hierarchical structure of pigskin
      collagen fibers by use of scanning electron microscopy (SEM), X-ray photoelectron
      spectroscopy (XPS), wide-angle X-ray diffraction (WAXD), confocal laser micro
      Raman spectroscopy (CLRS), and circular dichroism (CD). Our results demonstrate
      that the introduction of Cr3+ leads to the formation of a cluster of 20-40 nm
      between collagen fibrils, while the unique axial periodic structure (D
      periodicity) of the fibrils does not change. As the Cr3+ concentration increases,
      the order of intermolecular lateral packing, crystallite structure within helical
      chains, and N and C telopeptide regions decrease. The present study reveals that
      Cr3+ only cross-links with collagen but does not disrupt its triple helical
      structure.

PMID- 19603767
TI  - Novel morphology of calcium carbonate controlled by poly(L-lysine).
AB  - The novel calcium carbonate (CaCO(3)) morphology, twin-sphere with an equatorial
      girdle, has been obtained under the control of poly(L-lysine) (PLys) through gas
      diffusion method. The effect of the concentration of calcium cation and PLys, the
      reaction time, and the initial pH value are investigated, and various interesting
      morphologies, including twin-sphere, discus-like, hexagonal plate, and hallow
      structure are observed by using scanning electronic microscopy. Laser microscopic
      Raman spectroscopy studies indicated that all these CaCO(3) are vaterite. A
      possible mechanism is suggested to explain the formation of the twin-sphere based
      morphologies according to the results. It is proven that alkaline polypeptides
      can control the mineralization of CaCO(3) precisely as the reported acidic
      polypeptides and double hydrophilic block copolymers.

PMID- 19603769
TI  - Chain dynamics of a weakly adsorbing polymer in thin films.
AB  - Thin films of weakly adsorbing poly(dimethyl siloxane) (PDMS) on porous alumina
      are examined with NMR fast field cycling (FFC) relaxometry and NMR transverse
      relaxometry. The longitudinal relaxation dispersion of polymer amounts
      corresponding to approximate monolayer coverage shows substantial deviation from
      the bulk and is characterized by a particularly weak temperature dependence.
      Thicker films, however, show relaxation behavior and temperature dependence more
      similar to the bulk polymer. Transverse relaxation times were found to cover a
      range of several orders of magnitudes for any sample investigated; their
      dependence on temperature is a function of the total amount of adsorbed polymer.
      While thick films see an overall increase of molecular mobility at higher
      temperatures, monolayer films are best characterized by the decreasing fraction
      of a short, i.e. relatively rigid, component. These effects are consistent with
      the concept of two regions, one in which chain dynamics deviate from bulk and
      another where chain dynamics are reduced but bulk-like, although chains inside
      each region may also experience motional heterogeneity.

PMID- 19603770
TI  - New route for the preparation of Pd and PdAu nanoparticles using photoexcited Ti
      containing zeolite as an efficient support material and investigation of their
      catalytic properties.
AB  - A simple and unique route to synthesize nanosize Pd particles using a zeolite
      support including a single-site Ti oxide moiety (TS-1) under UV-light irradiation
      has been developed. By the photoassisted deposition (PAD) method, a Pd precursor
      can be deposited directly on the photoexcited tetrahedrally coordinated Ti oxide
      moiety within the zeolite frameworks from an aqueous solution of Pd. The
      subsequent reduction with H2 generates the nanosized Pd metal particles with a
      narrow size distribution (PAD-Pd/TS-1). Characterization by XAFS and TEM analysis
      revealed that the size of the metal particles depends on the preparation methods
      and that the smaller sizes of Pd nanoparticles were formed on the photodeposited
      catalysts compared with the conventionally prepared impregnated catalysts. PAD
      also provides PdAu bimetallic nanoparticles from an aqueous solution of mixture
      of PdCl2 and HAuCl4. The catalytic activities in the direct synthesis of hydrogen
      peroxide (H2O2) using H2 and O2 gases under atmospheric pressure were strongly
      dependent on the preparation method and the presence of Au atoms. Here, both
      deposition of PdAu onto the TS-1 moiety under UV-light irradiation was the most
      efficient for the above reaction. The applicability of the present catalytic
      system is highlighted by the one-pot reaction of phenol using PAD-Pd/TS-1 in the
      presence of H2 and O2, in which both Pd nanoparticles and isolated Ti oxide
      moieties within the frameworks participate in the formation of H2O2 and oxidation
      of phenol, respectively.

PMID- 19603771
TI  - Potential for tunable static and dynamic contact angle anisotropy on gradient
      microscale patterned topographies.
AB  - Translationally symmetric topographies can be designed to induce anisotropy of
      static and dynamic contact angles. The validity of ignoring directionality of
      topography in contact angle characterization was evaluated using microscale
      patterned topographies. Seven patterned topographies comprising elongated
      discontinuous microfeatures oriented along parallel paths and one topography
      comprising ridges were fabricated in a poly(dimethyl siloxane) elastomer (PDMSe).
      The static contact angle, advancing contact angle, receding contact angle,
      contact angle hysteresis, and slip angle were measured using water on each
      surface at three in-plane perspectives, with respect to the feature orientation.
      Static and dynamic contact angle anisotropies were investigated on the
      topographies to evaluate the effect of discontinuities along the feature lengths
      on the anisotropy that has been shown on channels or ridges in previous reports.
      Discontinuous feature topographies exhibited a statistically significant
      anisotropy of 2 degrees-6 degrees between the perpendicular and parallel
      directions, with respect to the static and dynamic contact angles. The ridges
      topography exhibited much larger 5 degrees-42 degrees anisotropy in the contact
      angles. The discontinuities along the feature lengths greatly reduced, but did
      not eliminate, the anisotropies compared to the ridges. This evidence of contact
      angle anisotropy indicates a need to identify the orientation of topography, in
      relation to contact angle measurements. It also implies a need to consider
      directionality in the design of microfluidic devices and self-cleaning surfaces.

PMID- 19603772
TI  - Indene formation from alkylated aromatics: kinetics and products of the
      fulvenallene + acetylene reaction.
AB  - A novel reaction is described for formation of the polyaromatic hydrocarbon (PAH)
      indene in aromatic flames, via the reaction of fulvenallene with acetylene
      (C2H2). Fulvenallene has been recently identified as the major decomposition
      product of the benzyl radical, the dominant intermediate in the oxidation of
      alkylated aromatic hydrocarbons, yet it is not presently included in kinetic
      models for aromatic oxidation or PAH/soot formation. Ab initio calculations with
      the G3B3 theoretical method show that acetylene adds to fulvenallene with a
      barrier of around 27 kcal mol(-1). This forms an activated C9H8 adduct that can
      rearrange to indene and dissociate to 1-indenyl + H with energy barriers below
      that of the entrance channel. Master equation simulations across a range of
      temperature and pressure conditions demonstrate that for temperatures relevant to
      combustion indene is the dominant product at high pressures while 1-indenyl + H
      dominate at lower pressures. At low to moderate temperatures, the production of
      collision stabilized cyclopentadiene-fulvene intermediates is also significant.
      The results presented in this study provide a new pathway to cyclopenta-fused
      PAHs in aromatic combustion and are expected to improve modeling of PAH and soot
      formation. The formation of cyclopenta-fused C5-C6 structures is required to
      describe the flame synthesis of carbon nanoparticles like fullerenes and
      buckybowls (corannulene). Improved rate expressions are also reported for the 1
      indenyl + H --> indene association reaction, and for the reverse dissociation,
      from variational transition state theory calculations. The new rate constants are
      significantly different than current estimates, primarily due to a re-evaluation
      of the indene C-H bond dissociation energy.

PMID- 19603773
TI  - Attenuated total reflectance FT-IR imaging and quantitative energy dispersive
      electron probe X-ray microanalysis techniques for single particle analysis of
      atmospheric aerosol particles.
AB  - This work demonstrates the practical applicability of the combined use of
      attenuated total reflectance (ATR) FT-IR imaging and low-Z particle electron
      probe X-ray microanalysis (EPMA) techniques for the characterization of
      individual aerosol particles. These two single particle analytical techniques
      provide complementary information on the physicochemical characteristics of the
      same individual particles, that is, the low-Z particle EPMA for the information
      on the morphology and elemental concentration and the ATR-FT-IR imaging on the
      functional group, molecular species, and crystal structure. It was confirmed that
      the ATR-FT-IR imaging technique can provide sufficient FT-IR absorption signals
      to perform molecular speciation of individual particles of micrometer size when
      applied to artificially generated aerosol particles such as ascorbic acid and
      NaNO(3) aerosols. An exemplar indoor atmospheric aerosol sample was investigated
      to demonstrate the practical feasibility of the combined application of ATR-FT-IR
      imaging and low-Z particle EPMA techniques for the characterization of individual
      airborne particles.

PMID- 19603774
TI  - Study of the mechanism of the N-CO photodissociation in N,N-dimethylformamide by
      direct trajectory surface hopping simulations.
AB  - Photodynamics of N,N-dimethylformamide (DMF) in its low-lying singlet excited
      n(O)-pi* and pi-pi* states have been explored by the direct trajectory surface
      hopping method based on multiconfigurational ab initio calculations. The dynamics
      simulations starting in the first excited singlet state (n(O)-pi*) showed that in
      57% of trajectories, S(1) excited DMF decays to the ground via the crossing seam
      related to the N-CO bond stretching MXS1. In 41% of all trajectories, the
      relaxation process on the S(1) PES moves the molecule into the minimum, where it
      stays trapped until the end of simulation time. In simulations starting in the
      second excited state, all trajectories are found to deactivate through MXS5
      (S(2)/S(1)) by very fast N-CO stretching. Because the N-CO dissociation process
      continues in the S(1) potential energy surface, most of the population overshoots
      the MXS1 and leads to fully dissociated electronically excited HCO and
      N(CH(3))(2) radicals. A mechanism for their deactivation by H-C-O and C-N-C
      bending modes is proposed.

PMID- 19603775
TI  - Room-temperature metal-hydride discharge source, with observations on NiH and
      FeH.
AB  - A metal sputtering source suitable for laboratory production of metal hydrides is
      described. Sputtering from pure nickel or iron in an Ar/H(2) discharge is
      analyzed at low resolution. High resolution laser excitation and dispersed
      fluorescence spectra of NiH have also been recorded. The source has been designed
      to operate with a ferromagnetic circuit for Zeeman spectroscopy. Signals from the
      source are strong enough to record dispersed fluorescence from NiH by Fourier
      transform interferometry in magnetic fields up to 1 T. We establish that FeH can
      also be formed in this source.

PMID- 19603776
TI  - Hydrogen activation by biomimetic diiron dithiolates.
AB  - Using the thermally stable salts of [Fe(2)(SR)(2)(CO)(3)(PMe(3))(dppv)]BAr(F)(4),
      we found that the azadithiolates [Fe(2)(adtR)(CO)(3)(PMe(3))(dppv)](+) react with
      high pressures of H(2) to give the hydride [Fe(2)(mu
      H)(adtR)(CO)(3)(dppv)(PMe(3))]BAr(F)(4). The related oxadithiolate and
      propanedithiolate complexes are unreactive toward H(2). Molecular hydrogen is
      proposed to undergo heterolysis assisted by the amine followed by isomerization
      of an initially formed terminal hydride. Use of H(2) and D(2)O gave the deuteride
      as well as the hydride, implicating protic intermediates.

PMID- 19603777
TI  - New heterometallic carboxylate frameworks: synthesis, structure, robustness,
      flexibility, and porosity.
AB  - Solvothermal reactions of cobalt acetate, alkali metal hydroxide, and isophthalic
      acid (H(2)ipa) in H(2)O/alcohol produce five new three-dimensional (3D)
      heterometallic carboxylate frameworks, namely, [Na(2)Co(ipa)(2)(MeOH)(2)](n) (1),
      [Na(2)Co(ipa)(2)(EtOH)(2)](n) (2), [Na(2)Co(ipa)(2)(H(2)O)(EtOH)](n) (3),
      [Li(2)Co(ipa)(2)(EtOH)](n) (4), and {[Li(2)Co(ipa)(2)(H(2)O)].H(2)O}(n) (5).
      Compounds 1-5 are all based on anionic [Co(ipa)(2)](n) square grids, which are
      linked by alkali metal ions in various manners to generate closely related but
      quite different 3D architectures. In addition to the carboxylate oxygen donors of
      the anionic [Co(ipa)(2)](n) square grids, the alkali metal ions are also
      coordinated by the MeOH, EtOH, or H(2)O ligands. The prototypical compound 1
      shows interesting solid-state structural transformations and sorption properties.
      The coordinated MeOH molecules in 1 can be easily substituted by moist H(2)O,
      accompanying a structural transformation from the chiral phase 1 to
      centrosymmetric phase 3. Further, thermal liberation of all MeOH ligands causes
      significant structural change and gives rise to a non-porous framework
      [CoNa(2)(ipa)(2)](n) (1'), which adsorbs MeOH, EtOH, and MeCN but not acetone
      based on the sizes of solvent molecules. Moreover, 1' can also selectively absorb
      CO(2) over N(2), H(2), and C(2)H(2), demonstrating the importance of oxophilic
      Na(I) ion in controlling the gate-opening behavior.

PMID- 19603778
TI  - Ligand dissociation: planar or pyramidal intermediates?
AB  - In organometallic chemistry, ligand dissociation is a key intermediate step in
      many useful processes. The dissociation of halide from an 18-electron half
      sandwich complex (that is, with a single cyclopentadienyl ligand) of the type
      [CpRu(P-P')Hal] leaves an unsaturated 16-electron intermediate [CpRu(P-P')](+),
      which is then ready for subsequent addition reactions. Does the intermediate
      maintain its structure with a vacant site in place of the dissociated ligand, or
      does it rearrange, either concurrent with its formation or subsequently? In other
      words, are the 16-electron species planar or pyramidal? The outcome is relevant
      for chiral-at-metal compounds [CpML(1)L(2)L(3)] because an intermediate
      [CpML(1)L(2)] retains its chirality with respect to the metal atom as long as it
      is pyramidal, whereas it loses its chiral information if it becomes planar. In
      this Account, we address experimental results and theoretical calculations that
      help illuminate the energetics of structural rearrangements after halide
      dissociation. The rate-determining step in the halide exchange and racemization
      reactions of (R(Ru))- and (S(Ru))-[CpRu(P-P')Cl] is the cleavage of the Ru-Cl
      bond to give pyramidal intermediates (R(Ru))- and (S(Ru))-[CpRu(P-P')](+), which
      have kept the original metal configurations. These unsaturated intermediates can
      react with added ligands, such as Br(-) or I(-) (k(2) paths). The substitution
      products form with retention of the metal configuration. However, the pyramidal
      intermediates (R(Ru))- and (S(Ru))-[CpRu(P-P')](+) can also invert to their
      mirror images (k(3) paths). For (R(Ru))- and (S(Ru))-[CpRu(P-P')](+), the barrier
      of the pyramidal inversion (k(3)) is much higher than that of the halide addition
      (k(2)). The competition ratio k(3)/k(2) determines how much racemization occurs
      in a ligand exchange reaction. The competition ratio k(3)/k(2) can be determined
      from the ratio of the (R(Ru))- and (S(Ru))-products, which is constant throughout
      the course of the reaction. For compounds like [CpRu(P-P')Hal], k(3)/k(2) is much
      smaller than 1, resulting in an energy profile that resembles a basilica. These
      results, established with chiral-at-metal compounds, are supported by
      calculations that show that 16-electron half-sandwich intermediates with sigma
      donating ligands, such as [CpM(NH(3))(2)], adopt planar structures, whereas
      strongly pi-bonding ligands, as in [CpM(CO)(2)], lead to pyramidal intermediates.
      The computed activation energies for the pyramidal inversion are on the order of
      10 kcal/mol, with the planar species being transition states. The ligand
      dissociation behavior of 18-electron transition metal complexes is compared with
      nucleophile dissociation in main group compounds with octet configurations; here
      we include new computational results. Without exception, unsaturated main group
      intermediates, such as the carbenium ions formed in S(N)1 reactions, are planar.
      Our results and analysis help put transition metal chemistry on a firmer
      mechanistic foundation, and chiral-at-metal compounds are invaluable to this end.

PMID- 19603779
TI  - Effects of heat treatment of calcium hydroxyapatite particles on the protein
      adsorption behavior.
AB  - The effects of heat treatment of calcium hydroxyapatite (Hap) on the protein
      adsorption behavior were examined using typical proteins of bovine serum albumin
      (BSA: isoelectric point (iep) = 4.7, molecular mass (Ms) = 67,200 Da, acidic
      protein), myoglobin (MGB: iep = 7.0, Ms = 17,800 Da, neutral protein), and
      lysozyme (LSZ: iep = 11.1, Ms = 14,600 Da, basic protein). The TEM, XRD, and gas
      adsorption measurements ascertained that all of the Hap particles examined were
      highly crystallized and nonporous. The Hap single phase was continued up to the
      heat treatment temperature of 600 degrees C. However, after treatment above 800
      degrees C in air, the beta-Ca3(PO4)2 (beta-TCP) phase slightly appeared. TG and
      ICP-AES measurements suggested that all of the Hap particles are Ca2+-deficient.
      Also, it was indicated from FTIR and XPS measurements that a partially dehydrated
      oxyhydroxyapatite (pd-OHap) was formed after treatment at high temperature. The
      saturated amounts of adsorbed BSA (nsBSA) did not vary on the Hap particles after
      heat treatment at 200 and 400 degrees C. However, nsBSA values were increased by
      raising the heat treatment temperature above 600 degrees C. The adsorption
      coverage of BSA was increased up to ca. 1.4. This adsorption coverage of BSA
      (thetaBSA) over unity suggests that the BSA molecules densely adsorbed and a part
      of BSA molecules adsorbed as end-on type on the Hap particle surface or BSA
      molecules became contracted. Similar adsorption behavior was observed on the LSZ
      system, but the adsorption coverage of LSZ (thetaLSZ) values are much less than
      thetaBSA. On the other hand, no effect of the heat treatment of Hap particles was
      observed on the adsorption of MGB. The increases of nsBSA and nsLSZ were
      explained by the increase of calcium and phosphate ions in the solutions
      dissolved from beta-TCP formed after heat treatment of Hap, especially treated at
      high temperature. The dissolved Ca2+ and PO(4)3 - ions may act as binders between
      proteins and Hap surfaces; the adsorption of Ca2+ ions on the Hap surface offers
      an adsorption site for BSA owing to its positive charge. In the case of
      adsorption of positively charged LSZ molecules, PO43- ions act as a binder in an
      opposite way. Since the MGB molecules are neutral, no binding effect of either
      ion was observed.

PMID- 19603781
TI  - Electrophilic addition and cyclization reactions of allenes.
AB  - Modern organic synthesis depends on the development of highly selective methods
      for the efficient construction of potentially useful target molecules. A primary
      goal in our laboratory is the discovery of new reactions that convert readily
      available starting materials to complex products with complete control of regio-
      and stereoselectivity. Allenes are one underused moiety in organic synthesis,
      because these groups are often thought to be highly reactive. However, many
      compounds containing the allene group, including natural products and
      pharmaceuticals, are fairly stable. The chemistry of allenes has been shown to
      have significant potential in organic synthesis. Electrophilic additions to
      allenes have often been considered to be synthetically less attractive due to the
      lack of efficient control of the regio- and stereoselectivity. However, this
      Account describes electrophilic reactions of allenes with defined regio- and
      stereoselectivity developed in our laboratory. Many substituted allenes are
      readily available from propargylic alcohols. Our work has involved an exploration
      of the reactions of these allenes with many different electrophiles: the E- or Z
      halo- or seleno-hydroxylations of allenyl sulfoxides, sulfones, phosphine oxides,
      carboxylates, sulfides or selenides, butenolides, and arenes, and the halo- or
      selenolactonization reactions of allenoic acids and allenoates. These reactions
      have produced a host of new compounds such as stereodefined allylic alcohols,
      ethers, amides, thiiranes, and lactones. In all these reactions, water acts as a
      reactant and plays an important role in determining the reaction pathway and the
      stereoselectivity. The differing electronic properties of the two C=C bonds in
      these allenes determine the regioselectivity of these reactions. Through
      mechanistic studies of chirality transfer, isolation and reactivity of cyclic
      intermediates, (18)O-labeling, and substituent effects, we discovered that the E
      stereoselectivity of some reactions results from the neighboring group
      participation of functional groups forming cyclic intermediates. We rationalize Z
      stereoselectivity under other conditions by soft Lewis acid-base interactions and
      steric effects. These electrophilic reactions of allenes are efficient and useful
      methods for the synthesis of stereodefined alkenes and lactones, useful
      functionalities for synthesis.

PMID- 19603782
TI  - Effect of water on structure of hydrophilic imidazolium-based ionic liquid.
AB  - The state of water in room-temperature ionic liquid, 1-ethyl-3-methylimidazolium
      tetrafluoroborate (EMI(+)BF(4)(-)), has been investigated by measurements of
      absorption and desorption isotherms, attenuated total reflectance infrared (ATR
      IR) spectroscopy, and (2)H NMR relaxation method. The absorption enthalpies of
      water for the ionic liquid were estimated from the absorption isotherms. The
      enthalpies in the water mole fraction range of x(w) <or= approximately 0.5 are
      lower than the enthalpy of vaporization for bulk water, but become larger than
      the value for bulk with increasing mole fraction of absorbed water. The ATR-IR
      spectra for EMI(+)BF(4)(-)-water solutions in the range of 0.09 <or= x(w) <or=
      0.34 have revealed that individual water molecules hydrogen-bonded to the anions
      predominate in the solutions at x(w) <or= approximately 0.2, while approximately
      30% of water molecules are hydrogen-bonded among them in the solutions at x(w) >
      approximately 0.3. In addition, the activation energies for the rotational motion
      of a water molecule estimated from the (2)H NMR relaxation rates have indicated
      that the motion of water molecules in EMI(+)BF(4)(-)-D(2)O solutions gradually
      becomes freer with increasing water content from x(w) = 0.10 to 0.30, but is
      retarded again at x(w) = 0.33. Therefore, all the present findings have suggested
      that the state of water molecules in EMI(+)BF(4)(-) significantly changes at x(w)
      approximately 0.3. On the other hand, to directly observe the effect of water on
      structure of EMI(+)BF(4)(-), LAXS experiments have been made on EMI(+)BF(4)(-)
      water solutions. It has been suggested that the interactions between the C(2)
      atom within the imidazolium ring of EMI(+) and BF(4)(-) are strengthened with
      increasing water content, while those at the C(4) and C(5) atoms weaken. Thus,
      the present LAXS experiments have clarified the beginning of formation of ion
      pair in EMI(+)BF(4)(-) by adding water at the molecular level.

PMID- 19603780
TI  - 2-Mercaptoacetylglycylglycyl (MAG2) as a bifunctional chelator for 99mTc-labeling
      of cyclic RGD dimers: effect of technetium chelate on tumor uptake and
      pharmacokinetics.
AB  - This report describes the synthesis of MAG(2)-PEG(4)-E[c(RGDfK)](2) (MAG(2)-P
      RGD(2): MAG(2) = S-benzoylmercaptoacetylglycylglycyl; PEG(4) = 15-amino-4,7,10,13
      tetraoxapentadecanoic acid) and MAG(2)-PEG(4)-E[PEG(4)-c(RGDfK)](2) (MAG(2)-3P
      RGD(2)), and the evaluation of (99m)TcO(MAG(2)-P-RGD(2)) and (99m)TcO(MAG(2)-3P
      RGD(2)) as new radiotracers for tumor imaging in the athymic nude mice bearing
      U87MG human glioma xenografts. We found that MAG(2) is such an efficient
      bifunctional chelating agent that (99m)TcO(MAG(2)-P-RGD(2)) and (99m)TcO(MAG(2)
      3P-RGD(2)) coul d be prepared in high yield (>90%) with high specific activity
      (~5 Ci/MUmol) using a kit formulation. (99m)TcO(MAG(2)-P-RGD(2)) and
      (99m)TcO(MAG(2)-3P-RGD(2)) have very high solution stability in the kit matrix.
      Biodistribution data in athymic nude mice bearing U87MG human glioma xenografts
      indicated that replacing the highly charged [(99m)Tc(HYNIC = 6-hydrazinonicotinyl
      and TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) with smaller
      (99m)TcO(MAG(2)) resulted in a significant increase in the radiotracer uptake in
      the tumor and normal organs most likely due to the higher lipophilicity of
      (99m)TcO(MAG(2)-3P-RGD(2)) (log P = -3.15 +/- 0.10) than that for [(99m)Tc(HYNIC
      3P-RGD(2))(tricine)(TPPTS)] ((99m)Tc-3P-RGD(2): log P = -3.96 +/- 0.05). Even
      though (99m)TcO(MAG(2)-3P-RGD(2)) has better tumor uptake (15.36 +/- 2.17 %ID/g
      at 60 min postinjection (p.i.)) than (99m)Tc-3P-RGD(2) (9.15 +/- 2.13 %ID/g at 60
      min p.i.), its tumor-to-background (T/B) ratios (tumor/blood = 13.52 +/- 4.57;
      tumor/liver = 4.25 +/- 0.88; tumor/lung = 3.17 +/- 0.60; and tumor/muscle = 8.34
      +/- 2.34) are not as good as those of (99m)Tc-3P-RGD(2) (tumor/blood = 36.0 +/-
      11.5; tumor/liver = 5.14 +/- 1.46; tumor/lung = 4.36 +/- 0.54; and tumor/muscle =
      13.70 +/- 2.21) at 60 min p.i. On the basis of these results, we believe that
      (99m)Tc-3P-RGD(2) remains a better radiotracer because of its higher T/B ratios.

PMID- 19603783
TI  - A remarkable member of the polyoxometalates: the eight-nickel-capped alpha-keggin
      polyoxoazonickelate.
AB  - The eight-nickel-capped polyoxoazonickelate,
      [Ni(20)(OH)(24)(MMT)(12)(SO(4))](NO(3))(2).6H(2)O (1; MMT = 2-mercapto-5-methyl
      1,3,4-thiadiazole), has been synthesized, which has an alpha-Keggin structure
      with eight nickel caps. In this structure, the polyatom is the late transition
      metal Ni(II); the central heteroatom is S, and the organic terminal ligand
      becomes the primary part of the Keggin structure. This is a Keplerate-type
      cluster, which shows a central Ni(II)(12) cuboctahedron formed by the 12 Ni(II)
      centers of the classical alpha-Keggin core and a Ni(II)(8) hexahedron formed by
      the eight nickel caps.

PMID- 19603784
TI  - Interaction of poly(L-arginine) with negatively charged DPPG membranes:
      calorimetric and monolayer studies.
AB  - The interaction of poly(L-arginine) (PLA) with dipalmitoyl-phosphatidylglycerol
      (DPPG) bilayer membranes and monolayers was studied by differential scanning
      calorimetry (DSC), isothermal titration calorimetry (ITC), and monolayer
      experiments. The binding of PLA affected the main transition temperature of lipid
      bilayers (T(m)) only marginally. Depending on the PLA chain length, T(m) was
      slightly increased or decreased. This finding was attributed to the superposition
      of two counteracting effects on the transition after PLA binding. The main
      transition enthalpy (DeltaH(m)) was decreased upon PLA binding and the formation
      of a ripple phase (P(beta)') was suppressed. ITC experiments showed that two
      distinct processes are involved in binding of PLA to gel phase (L(beta)')
      membranes. At low peptide content the binding reaction is endothermic, and at
      high peptide concentration the binding becomes exothermic. However, the enthalpy
      of binding to fluid (L(alpha)) membranes was exothermic for all peptide-to-lipid
      ratios. The temperature dependence of PLA binding to fluid palmitoyl-oleoyl
      phosphatidylglycerol (POPG) membranes showed a decrease in binding enthalpy with
      increasing temperature (Delta(R)C(p) < 0), indicating hydrophobic contributions
      to the free energy of binding. For longer PLA chains, the binding enthalpy for
      L(alpha) membranes was more exothermic than for shorter chains. Monolayer
      adsorption experiments showed two consecutive binding processes. At low initial
      surface pressures (pi(0)) a condensation of the lipid film (Deltapi < 0) is first
      observed after PLA injection into the subphase, followed by an increase in film
      pressure (Deltapi > 0) due to insertion of peptide side chains into the
      monolayer. At higher pi(0) only an increase in film pressure can be observed due
      to the insertion of the side chains. Deltapi increases with increasing pi(0). The
      insertion of the peptide into the monolayer is corroborated by the observed shift
      of pi-A isotherms to higher molecular areas. All presented experiments show that
      the binding of PLA to DPPG membranes has not only electrostatic but also
      nonelectrostatic contributions.

PMID- 19603786
TI  - FRET enhancement in multilayer core-shell nanoparticles.
AB  - This study describes the preparation and characterization of novel multilayer
      core-shell nanoparticles displaying metal-enhanced Forster resonant energy
      transfer. The increase in range and efficiency of Forster resonant energy
      transfer in these fluorescent nanocomposites and their vastly improved luminosity
      make them promising optical probes for a variety of applications such as cell
      imaging and biosensing.

PMID- 19603785
TI  - Multidomain peptides as single-walled carbon nanotube surfactants in cell
      culture.
AB  - We present a series of short, multidomain peptides as biocompatible solubilizing
      agents of single-walled carbon nanotubes (SWCNTs). These peptides are organized
      into an ABA block motif, where the A block is composed of charged amino acids,
      such as glutamic acid, and the B block is composed of alternating hydrophilic and
      hydrophobic residues. The hydrophobic amino acid residues interact with SWCNT
      sidewalls, while the hydrophilic residues interact primarily with water in an
      aqueous solution. When many peptides assemble along the length of the nanotube,
      it becomes effectively encapsulated within a peptide nanofiber. This noncovalent
      interaction between the peptide and the nanotube solubilizes SWCNTs while keeping
      the electronic structure of the nanotube intact, thereby preserving the optical
      and electrical properties that make SWCNTs promising for use in biological
      applications. To assess the toxicity of these peptide coatings, they were added
      to cultures of NIH 3T3 mouse fibroblasts and the effect on cell viability was
      measured. Toxicity was found to be far lower than for ionic surfactants typically
      used for SWCNT suspension and similar to Pluronics. The near-IR fluorescence
      intensity of SWCNTs in peptide suspensions was comparable to that in Pluronics.
      Five surfactants were tested for their effect on the proliferation of NIH 3T3
      cells with and without SWCNTs. Although some differences were observed among
      surfactants, in no case did the presence of SWCNTs make a statistically
      significant difference. Based on their ability to solubilize SWCNTs, the
      fluorescence of the suspended tubes, their minimal impact on cell viability, and
      their potential for easy chemical modification, multidomain peptides have been
      found to have excellent potential as a biocompatible surfactant for suspension of
      SWCNTs.

PMID- 19603787
TI  - Conduction pathway of pi-stacked ethylbenzene molecular wires on Si(100).
AB  - One of the most important challenges of molecular electronics is to enable
      systematic fabrication of molecular functional components on well-characterized
      solid-state substrates in a controlled manner. Recently, experimental techniques
      were developed to achieve such fabrication where lines of pi-stacked ethylbenzene
      molecules are induced to self-assemble on an H-terminated Si(100) surface at
      precise locations and along precise directions. In this work, we theoretically
      analyze charge transport properties of these ethylbenzene wires using a state-of
      the-art first-principles technique where density functional theory (DFT) is used
      within the nonequilibrium Green's function formalism (NEGF). Our device model
      consists of ethylbenzene stacks bonded to an H-terminated Si(100) surface and
      bridging two metal leads. The electron transmission spectrum and its associated
      scattering states as well as the resistance of the molecular wire are determined
      by the self-consistent NEGF-DFT formalism. The transmission spectrum has a
      resonance nature for energies around the highest occupied molecular orbital
      (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the ethylbenzene
      wires. However, near the Fermi level of the device, which sits inside the HOMO
      LUMO gap, the Si substrate is found to play an important role in providing
      additional pathways for conduction. It has emerged that, within our model system,
      the transmission peak nearest to the Fermi level corresponds to transport through
      the Si substrate and not the pi-stacked molecular line. The low-bias resistance R
      is found to increase exponentially with the length of the molecular line n, as R
      approximately e(betan), indicating a tunneling behavior in conduction. We further
      found that the exponential scaling has two regimes characterized by two different
      scaling parameters beta: a high value for conduction through the molecular stack
      in short lines and a lower value for conduction through the substrate in longer
      lines. Our results suggest that when the conduction of molecular wires bonded to
      semiconductor substrates is theoretically analyzed, conduction pathways through
      the substrate need to be taken into account.

PMID- 19603788
TI  - Missing metallofullerene with C80 cage.
AB  - Many insoluble metallofullerenes are called missing metallofullerenes. These
      metallofullerenes have not yet been isolated despite their detection in raw soot
      using mass spectrometry. They have been anticipated to show unique structures and
      properties that differ considerably from those of soluble metallofullerenes.
      Herein, a missing metallofullerene, La@C(80), was extracted and isolated as a
      derivative, La@C(80)(C(6)H(3)Cl(2)). The structure of La@C(80)(C(6)H(3)Cl(2)) was
      determined unambiguously using single-crystal X-ray crystallographic analysis. In
      fact, La@C(80) has a novel C(80) cage, C(2v)-C(80) (80:3), which has not been
      reported. The calculation of La@C(80) with C(2v)-C(80) (80:3) cage shows that
      La@C(2v)-C(80) (80:3) has a radical character as well as small ionization
      potential (Ip) and electron affinity (Ea), which are indicative of high
      reactivity. On the basis of those results, La@C(2v)-C(80) (80:3) is expected to
      interact strongly and bond with amorphous carbon or other fullerenes in soot that
      is made insoluble in common organic solvents.

PMID- 19603789
TI  - Adsorption of azothiophene dye having an N-bridging bidentate tail group on gold.
AB  - The novel azothiophene derivatives [AT-di(CnSAc) (n=6 and 12)], an azo linkage
      (N=N) that bridges one phenyl ring with an N-bridging dialkylthioacetate tail and
      one thiophene ring, are synthesized and characterized. The azothiophene
      derivatives substituted with electron-withdrawing groups are blue in color,
      exhibit a bathochromic shift of a longer wavelength, and are electrochemically
      active. The formation and characterization of AT-di(CnSAc) SAMs with a bidentate
      tail group of the N-bridging dialkylthioacetate have been studied by surface
      sensitive techniques such as grazing angle Fourier transform infrared (FT-IR), a
      quartz crystal microbalance (QCM), spectroscopic ellipsometry, X-ray
      photoelectron spectroscopy (XPS), and cyclic voltammetry (CV). It has been shown
      that the adsorption reaction of the thioacetate group is almost spontaneous and
      the N-bridging dialkylthioacetate SAMs with longer methylene length have a
      packing density higher than that with a shorter methylene length. However, the
      sulfur tethers of the N-bridging dialkylthioacetate show incomplete binding of
      sulfur atoms in AT-di(CnSAc) SAMs.

PMID- 19603791
TI  - Nanofluidic diodes based on nanotube heterojunctions.
AB  - The mechanism of tuning charge transport in electronic devices has recently been
      implemented into the nanofluidic field for the active control of ion transport in
      nanoscale channels/pores. Here we report the first synthesis of longitudinal
      heterostructured SiO(2)/Al(2)O(3) nanotubes. The ionic transport through these
      nanotube heterojunctions exhibits clear current rectification, a signature of
      ionic diode behavior. Such nanofluidic diodes could find applications in ion
      separation and energy conversion.

PMID- 19603790
TI  - Discovery of inhibitors of lupin diadenosine 5',5'''-P(1),P(4)-tetraphosphate
      hydrolase by virtual screening.
AB  - Novel inhibitors of lupin diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A)
      hydrolase have been identified by in silico screening of a large virtual chemical
      library. Compounds were ranked on the basis of a consensus from six scoring
      functions. From the top 100 ranked compounds six were selected and initially
      screened for inhibitory activity using a single concentration isothermal
      titration calorimetry assay. Two of these compounds that showed excellent
      solubility properties were further analyzed, but only one [NSC51531; 2-((8
      hydroxy-4-(4-methyl-2-sulfoanilino)-9,10-dioxo-9,10-dihydro-1-anthracenyl)amino)
      5-methylbenzenesulfonic acid] exhibited competitive inhibition with a K(i) of 1
      microM. A structural analogue of this compound also exhibited competitive
      inhibition with a comparable K(i) of 2.9 microM. (1)H, (15)N NMR spectroscopy was
      used to map the binding site of NSC51531 on lupin Ap(4)A hydrolase and
      demonstrated that the compound bound specifically in the substrate-binding site,
      consistent with the competitive inhibition results. Binding of NSC51531 to the
      human form of Ap(4)A hydrolase is nonspecific, suggesting that this compound may
      represent a useful lead in the design of specific inhibitors of the plant-like
      form of Ap(4)A hydrolases.

PMID- 19603792
TI  - Modeling an electronic conductor based on natural peptide sequences.
AB  - In this work we used quantum mechanical calculations, molecular dynamics
      simulations, and QM/MM methods to examine the formation of a pi-stacking ladder
      and the existence of charge transfer processes in a tubular nanostructure
      constructed using protein building blocks. Initially, the conformational
      properties of beta-3-thienylalanine, a synthetic amino acid with an aromatic side
      group, were studied using quantum mechanical calculations. Next, this amino acid
      was used to substitute the natural residues at selected positions of the
      nanotube. Molecular dynamics simulations showed that a rational design of the
      targeted replacements enhances the stability of the tubular nanostructure and
      forms a pi-stacking ladder in the inner core of the tube. Finally, QM/MM
      calculations on the oxidized nanotube evidenced the delocalization of the pi
      electron deficiency between the thienyl side groups of the different synthetic
      residues. The overall results reflected that the system under study is a
      potential candidate to be used as a nanowire.

PMID- 19603793
TI  - CdSe quantum dot sensitized solar cells. Shuttling electrons through stacked
      carbon nanocups.
AB  - The charge separation between excited CdSe semiconductor quantum dots and stacked
      cup carbon nanotubes (SCCNTs) has been successfully tapped to generate
      photocurrent in a quantum dot sensitized solar cell (QDSC). By employing an
      electrophoretic deposition technique we have cast SCCNT-CdSe composite films on
      optically transparent electrodes (OTEs). The quenching of CdSe emission, as well
      as transient absorption measurements, confirms ultrafast electron transfer to
      SCCNTs. The rate constant for electron transfer increases from 9.51 x 10(9) s(-1)
      to 7.04 x 10(10) s(-1) as we decrease the size of CdSe nanoparticles from 4.5 to
      3 nm. The ability of SCCNTs to collect and transport electrons from excited CdSe
      has been established from photocurrent measurements. The morphological and
      excited state properties of SCCNT-CdSe composites demonstrate their usefulness in
      energy conversion devices.

PMID- 19603794
TI  - Plasmon dispersion in coaxial waveguides from single-cavity optical transmission
      measurements.
AB  - We determine the plasmon dispersion relation in coaxial waveguides composed of a
      circular channel separating a metallic core and cladding. Optical transmission
      measurements are performed on isolated coaxial nanoapertures fabricated on a Ag
      film using focused ion-beam lithography. The dispersion depends strongly on the
      dielectric material and layer thickness. Our experimental results agree well with
      an analytical model for plasmon dispersion in coaxial waveguides. We observe
      large phase shifts at reflection from the end facets of the coaxial cavity, which
      strongly affect the waveguide resonances and can be tuned by changing the coax
      geometry, composition, and surrounding dielectric index, enabling coaxial
      cavities with ultrasmall mode volumes.

PMID- 19603795
TI  - Addition of beta-malic acid-containing poly(ethylene glycol) dimethacrylate to
      form biodegradable and biocompatible hydrogels.
AB  - Poly(malic acid) is water-soluble, functionalizable, and biodegradable, making it
      attractive as a precursor of hydrogels for biomedical applications. However,
      homopoly(malic acid), with pK(1/2) of 4.3, is too acidic for biocompatibility. To
      overcome the acidity, we have synthesized beta-malic acid-containing
      poly(ethylene glycol) dimethacrylate (PEGMAc) with pK(a) of 5.02. Solutions of
      methacrylated O-carboxymethylchitosan (OCMCS), PEGMAc, and poly(ethylene glycol)
      diacrylate (PEGDA; 7:7:86 and 6:20:74 (w/w/w)) in water (80%) have near neutral
      pHs (6.8-6.9). These solutions form firm hydrogels when photopolymerized. These
      are referred to as O7-PEGMAc7-B86 and O6-PEGMAc20-B74 (where the numerals refer
      to the weight content of each component, O is OCMCS and B is PEGDA added to make
      blend). The carboxyl groups in PEGMAc permit the surface grafting of hydrogels
      with Arg-Gly-Asp (RGD). The cytocompatibilities of smooth muscle cells (SMCs) on
      RGD-grafted hydrogels were studied. From the tetrazolium salt reduction assay, O6
      PEGMAc20-B74 was found to have significantly better 10th day cytocompatibility
      compared to hydrogels containing lower or no PEGMAc. These gels degrade upon
      hydrolysis releasing malic acid, PEG and OCMCS. The increased cell compatibility
      of O6-PEGMAc20-B74 is possibly due to increased surface RGD content and near
      neutral pH even during biodegradation. Our novel PEGMAc-modified blends are a
      promising functionalizable biodegradable hydrogel precursor providing improved
      cell proliferation.

PMID- 19603796
TI  - NMR structure and dynamics of the engineered fluorescein-binding lipocalin FluA
      reveal rigidification of beta-barrel and variable loops upon enthalpy-driven
      ligand binding.
AB  - The NMR structure of the 21 kDa lipocalin FluA, which was previously obtained by
      combinatorial design, elucidates a reshaped binding site specific for the dye
      fluorescein resulting from 21 side chain replacements with respect to the
      parental lipocalin, the naturally occurring bilin-binding protein (BBP). As
      expected, FluA exhibits the lipocalin fold of BBP, comprising eight antiparallel
      beta-strands forming a beta-barrel with an alpha-helix attached to its side.
      Comparison of the NMR structure of free FluA with the X-ray structures of
      BBP.biliverdin IX(gamma) and FluA.fluorescein complexes revealed significant
      conformational changes in the binding pocket, which is formed by four loops at
      the open end of the beta-barrel as well as adjoining beta-strand segments. An
      "induced fit" became apparent for the side chain conformations of Arg 88 and Phe
      99, which contact the bound fluorescein in the complex and undergo concerted
      rearrangement upon ligand binding. Moreover, slower internal motional modes of
      the polypeptide backbone were identified by measuring transverse (15)N backbone
      spin relaxation times in the rotating frame for free FluA and also for the
      FluA.fluorescein complex. A reduction in the level of such motions was detected
      upon complex formation, indicating rigidification of the protein structure and
      loss of conformational entropy. This hypothesis was confirmed by isothermal
      titration calorimetry, showing that ligand binding is enthalpy-driven, thus
      overcompensating for the negative entropy associated with both ligand binding per
      se and rigidification of the protein. Our investigation of the solution structure
      and dynamics as well as thermodynamics of lipocalin-ligand interaction not only
      provides insight into the general mechanism of small molecule accommodation in
      the deep and narrow cavity of this abundant class of proteins but also supports
      the future design of corresponding binding proteins with novel specificities, so
      called "anticalins".

PMID- 19603797
TI  - Model study on transesterification of soybean oil to biodiesel with methanol
      using solid base catalyst.
AB  - Modeling of the transesterification of vegetable oils to biodiesel using a solid
      base as a catalyst is very important because the mutual solubilities of oil and
      methanol will increase with the increasing biodiesel yield. The heterogeneous
      liquid-liquid-solid reaction system would become a liquid-solid system when the
      biodiesel reaches a certain content. In this work, we adopted a two-film theory
      and a steady state approximation assumption, then established a heterogeneous
      liquid-liquid-solid model in the first stage. After the diffusion coefficients on
      the liquid-liquid interface and the liquid-solid interface were calculated on the
      basis of the properties of the system, the theoretical value of biodiesel
      productivity changing with time was obtained. The predicted values were very near
      the experimental data, which indicated that the proposed models were suitable for
      the transesterification of soybean oil to biodiesel when solid bases were used as
      catalysts. Meanwhile, the model indicated that the transesterification reaction
      was controlled by both mass transfer and reaction. The total resistance will
      decrease with the increase in biodiesel yield in the liquid-liquid-solid stage.
      The solid base catalyst exhibited an activation energy range of 9-20 kcal/mol,
      which was consistent with the reported activation energy range of homogeneous
      catalysts.

PMID- 19603799
TI  - A novel Prins cyclization through benzylic/allylic C-H activation.
AB  - A step-economic method to construct the tetrahydropyran ring, involving
      sequential benzylic/allylic C-H bond activation via DDQ oxidation and
      nucleophilic attack of an unactivated olefin, is described. The equatorial
      trisubstituted Prins products are obtained from benzyl and allyl homoallylic
      ethers with high yield and stereochemical fidelity.

PMID- 19603800
TI  - Liposome-hydrogel bead complexes prepared via biotin-avidin conjugation.
AB  - Liposomes immobilized onto polymeric hydrogel microbeads have potential
      advantages both in tissue engineering applications and as drug delivery vehicles.
      Here we demonstrate, quantify, and optimize lipid vesicle binding to polymeric
      hydrogel microbeads via the avidin-biotin conjugation system and characterize the
      stability of the resulting microgel-bound liposomes. Microgels consisting of a
      copolymer of N-isopropylacrylamide (NIPAM) and acrylic acid (AA), cross-linked
      with bis-acrylamide, that is, p(NIPAM-co-AA), were biotinylated using aqueous
      carbodiimide chemistry. Extruded liposomes consisting of 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) plus a small fraction of a biotin-derivatized
      phosphatidylethanolamine (B-PE) were saturated with avidin and allowed to bind to
      biotinylated hydrogel beads. Using a combination of fluorescence spectroscopy,
      quenching, and microscopy and 31P NMR static and magic angle spinning (MAS)
      spectroscopies, we demonstrate conditions for near-quantitative liposome binding
      to p(NIPAM-co-AA) microbeads and show that liposome fusion does not occur under
      such conditions, that the liposomes remain intact and impermeable when so bound,
      and that they can function as slow release vehicles for entrapped aqueous
      species.

PMID- 19603801
TI  - Strong metal ion size based selectivity of the highly preorganized ligand PDA
      (1,10-phenanthroline-2,9-dicarboxylic acid) with trivalent metal ions. A
      crystallographic, fluorometric, and thermodynamic study.
AB  - The selectivity of the rigid ligand PDA (1,10-phenanthroline-2,9-dicarboxylic
      acid) for some M(III) (M = metal) ions is presented. The structure of
      [Fe(PDA(H)(1/2))(H(2)O)(3)] (ClO(4))(2).3H(2)O.(1)/(2)H(5)O(2) (1) is reported:
      triclinic, P1, a = 7.9022(16) A, b = 12.389(3) A, c = 13.031(3) A, alpha =
      82.55(3) degrees , beta = 88.41(3) degrees , gamma = 78.27(3) degrees , V =
      1238.6(4) A(3), Z = 2, R = 0.0489. The coordination geometry around the Fe(III)
      is close to a regular pentagonal bipyramid, with Fe-N lengths averaging 2.20 A,
      which is normal for a 1,10-phenanthroline type of ligand coordinated to seven
      coordinate Fe(III). The Fe-O bonds to the carboxylate oxygens average 2.157 A,
      which is rather long compared to the average Fe-O length of 2.035 A to
      carboxylates in seven-coordinate Fe(III) complexes. The structure of 1 supports
      the idea that the Fe(III) is too small for ideal coordination in the cleft of
      PDA, and the structure shows that the Fe(III) adapts to this by inducing numerous
      small distortions in the structure of the PDA ligand. The log K(1) values for PDA
      at 25 degrees C in 0.1 M NaClO(4) were determined by UV spectroscopy with Al(III)
      (log K(1) = 6.9), Ga(III) (log K(1) = 9.7), In(III) (log K(1) = 19.7), Fe(III)
      (log K(1) = 20.0), and Bi(III) (log K(1) = 26.2). The low values of log K(1) for
      PDA with Al(III) and Ga(III) are because these ions are too small for the cleft
      in PDA, which requires a large metal ion with an ionic radius (r(+)) of 1.0 A.
      In(III) and Fe(III) (r(+) = 0.86 and 0.72 A for a coordination number (CN) of 7)
      are somewhat too small for the cleft in PDA but may adapt by increasing the
      coordination number, which increases the metal ion size, and have high log K(1)
      values. Very large log K(1) values are found, as expected, for Bi(III) (r(+) =
      1.17 A, CN = 8), which fits the cleft quite well. Fluorescence studies show that
      Y(III) produces the largest CHEF (chelation enhanced fluorescence) effects,
      followed by La(III) and Lu(III), in the PDA complexes. Metal ions with nonfilled
      d or f subshells produce very large quenching of the fluorescence, as do heavy
      metal ions such as In(III) and Bi(III), which have large spin-orbit coupling
      effects. The Al(III)/PDA complex produced an intense broad band at longer
      wavelength than the pi*-pi emissions of the PDA ligand, which is at a maximum at
      pH 6, and the possibility that this might reflect an exciplex, where one PDA
      ligand in the Al(III) complex pi-stacks with the excited state of a second PDA
      ligand, is discussed.

PMID- 19603803
TI  - Internal electrostatic control of the primary charge separation and recombination
      in reaction centers from Rhodobacter sphaeroides revealed by femtosecond
      transient absorption.
AB  - We report the observation of two conformational states of closed RCs from
      Rhodobacter sphaeroides characterized by different P(+)H(A)(-) --> PH(A) charge
      recombination lifetimes, one of which is of subnanosecond value (700 +/- 200 ps).
      These states are also characterized by different primary charge separation
      lifetimes. It is proposed that the distinct conformations are related to two
      protonation states either of reduced secondary electron acceptor, Q(A)(-), or of
      a titratable amino acid residue localized near Q(A). The reaction centers in the
      protonated state are characterized by faster charge separation and slower charge
      recombination when compared to those in the unprotonated state. Both effects are
      explained in terms of the model assuming modulation of the free energy level of
      the state P(+)H(A)(-) by the charges on or near Q(A) and decay of the P(+)H(A)(-)
      state via the thermally activated P(+)B(A)(-) state.

PMID- 19603802
TI  - Combined high-resolution neutron and X-ray analysis of inhibited elastase
      confirms the active-site oxyanion hole but rules against a low-barrier hydrogen
      bond.
AB  - To help resolve long-standing questions regarding the catalytic activity of the
      serine proteases, the structure of porcine pancreatic elastase has been analyzed
      by high-resolution neutron and X-ray crystallography. To mimic the tetrahedral
      transition intermediate, a peptidic inhibitor was used. A single large crystal
      was used to collect room-temperature neutron data to 1.65 A resolution and X-ray
      data to 1.20 A resolution. Another crystal provided a low-temperature X-ray data
      set to 0.94 A resolution. The neutron data are to higher resolution than
      previously reported for a serine protease and the X-ray data are comparable with
      other studies. The neutron and X-ray data show that the hydrogen bond between
      His57 and Asp102 (chymotrypsin numbering) is 2.60 A in length and that the
      hydrogen-bonding hydrogen is 0.80-0.96 A from the histidine nitrogen. This is not
      consistent with a low-barrier hydrogen which is predicted to have the hydrogen
      midway between the donor and acceptor atom. The observed interaction between
      His57 and Asp102 is essentially a short but conventional hydrogen bond, sometimes
      described as a short ionic hydrogen bond. The neutron analysis also shows that
      the oxygen of the oxopropyl group of the inhibitor is present as an oxygen anion
      rather than a hydroxyl group, supporting the role of the "oxyanion hole" in
      stabilizing the tetrahedral intermediate in catalysis.

PMID- 19603804
TI  - Influence of the "host-guest" interactions on the mobility of genistein/beta
      cyclodextrin inclusion complex.
AB  - Inclusion complexes of cyclodextrins with nonpolar drugs are a topic of current
      interest in pharmaceutical science, because they increase the aqueous solubility,
      chemical stability and bioavailability of poorly water-soluble drugs. By means of
      elastic incoherent neutron scattering (EINS) technique on the backscattering
      spectrometer IN13, we measured, in the 150-340 K temperature range, the mean
      square displacements (MSD) of hydrogen atoms derived from elastic spectra of
      inclusion complex of beta-cyclodextrin (beta-CyD) with genistein (Gen), a
      phytoestrogen of great interest for its antioxidant, anticarcinogenic and
      antiosteoporotic activities. The mobility of the complex has been compared with
      the single components and the physical mixture. The elastic intensity has been
      interpreted in terms of the double-well model in the whole temperature range. In
      the case of Gen, a mainly vibrational dynamics is revealed, while for the other
      samples, the elastic intensity becomes non-Gaussian above a temperature T(d)
      congruent with 220-230 K. This dynamical activation, which is represented by an
      Arrhenius trend, seems to be promoted by the crystallization water molecules. The
      dynamics of the Gen/beta-CyD inclusion complex is restricted with respect to the
      physical mixture, due to the action of specific "host-guest" interactions upon
      complexation. Finally, the dynamical response of our systems to temperature is
      put in relationship with their thermal stability.

PMID- 19603805
TI  - Rationalizing lead optimization by associating quantitative relevance with
      molecular structure modification.
AB  - Historically, one of the characteristic activities of the medicinal chemist has
      been the iterative improvement of lead compounds until a suitable therapeutic
      entity is achieved. Often referred to as lead optimization, this process
      typically takes the form of minor structural modifications to an existing lead in
      an attempt to ameliorate deleterious attributes while simultaneously trying to
      maintain or improve desirable properties. The cumulative effect of this exercise
      performed over the course of several decades of pharmaceutical research by
      thousands of trained researchers has resulted in large collections of
      pharmaceutically relevant chemical structures. As far as the authors are aware,
      this work represents the first attempt to use that data to define a framework to
      quantifiably catalogue and summate this information into a medicinal chemistry
      expert system. A method is proposed that first comprehensively mines a compendium
      of chemical structures compiling the structural modifications, abridges them to
      rectify artificially inflated support levels, and then performs an association
      rule mining experiment to ascribe relative confidences to each transformation.
      The result is a catalogue of statistically relevant structural modifications that
      can potentially be used in a number of pharmaceutical applications.

PMID- 19603806
TI  - Low-temperature solution-processed amorphous indium tin oxide field-effect
      transistors.
AB  - Amorphous indium tin oxide (ITO)-based thin-film transistors (TFTs) were
      fabricated on various dielectrics [SiO(2) and self-assembled nanodielectrics
      (SANDs)] by spin-coating an ITO film precursor solution consisting of InCl(3) and
      SnCl(4) as the sources of In(3+) and Sn(4+), respectively, methoxyethanol
      (solvent), and ethanolamine (base). These films can be annealed at temperatures
      T(a) < or = 250 degrees C and afford devices with excellent electrical
      characteristics. The optimized [In(3+)]/[In(3+) + Sn(4+)] molar ratio (0.7) and
      annealing temperature (T(a) = 250 degrees C) afford TFTs exhibiting electron
      mobilities of approximately 2 and approximately 10-20 cm(2) V(-1) s(-1) with
      SiO(2) and SAND, respectively, as the gate dielectric. Remarkably, ITO TFTs
      processed at 220 degrees C still exhibit electron mobilities of >0.2 cm(2) V(-1)
      s(-1), which is encouraging for processing on plastic substrates.

PMID- 19603807
TI  - Determining the effect of calcium cations on acrylamide formation in cooked wheat
      products using a model system.
AB  - A model system was used to cook wheat flour and water dough pieces in sealed
      pressure tubes under controlled pH conditions and with various additives in the
      recipe water to determine acrylamide (AA) formation and elimination. The
      potential effectiveness of calcium as CaCl2 or CaCO3 salts to reduce the
      formation of AA in wheat based food products was assessed. Since the divalent
      Ca2+ was capable of inducing significant pH reduction in the dough, and pH
      lowering is known to reduce AA formation, it was necessary in some cases to
      adjust the pH before cooking or use a pH matched control. For comparison, the
      effect of NaCl on AA formation was also determined. It was found that AA
      reduction up to 36% was obtained by adding CaCl2 to the recipe water at a 0.04 M
      concentration, compared to 23% for 0.04 M NaCl, and there was no reduction when
      CaCO3 was added to simulate a calcium enriched flour.

PMID- 19603808
TI  - Viral capsid DNA aptamer conjugates as multivalent cell-targeting vehicles.
AB  - Nucleic acid aptamers offer significant potential as convenient and evolvable
      targeting groups for drug delivery. To attach them to the surface of a genome
      free viral capsid carrier, an efficient oxidative coupling strategy has been
      developed. The method involves the periodate-mediated reaction of phenylene
      diamine substituted oligonucleotides with aniline groups installed on the outer
      surface of the capsid shells. Up to 60 DNA strands can be attached to each viral
      capsid with no apparent loss of base-pairing capabilities or protein stability.
      The ability of the capsids to bind specific cellular targets was demonstrated
      through the attachment of a 41-nucleotide sequence that targets a tyrosine kinase
      receptor on Jurkat T cells. After the installation of a fluorescent dye on the
      capsid interior, capsids bearing the cell-targeting sequence showed significant
      levels of binding to the cells relative to those of control samples.
      Colocalization experiments using confocal microscopy indicated that the capsids
      were endocytosed and trafficked to lysosomes for degradation. These observations
      suggest that aptamer-labeled capsids could be used for the targeted drug delivery
      of acid-labile prodrugs that would be preferentially released upon lysosomal
      acidification.

PMID- 19603809
TI  - Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}
      4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent,
      orally available cyclin dependent kinase inhibitor.
AB  - The discovery of a novel class of inhibitors of cyclin dependent kinases (CDKs)
      is described. Starting from compound 1, showing good potency as inhibitor of CDKs
      but being poorly selective against a panel of serine-threonine and tyrosine
      kinases, new analogues were synthesized. Enhancement in selectivity,
      antiproliferative activity against A2780 human ovarian carcinoma cells, and
      optimization of the physical properties and pharmacokinetic profile led to the
      identification of highly potent and orally available compounds. Compound 28 (PHA
      848125), which in the preclinical xenograft A2780 human ovarian carcinoma model
      showed good efficacy and was well tolerated upon repeated daily treatments, was
      identified as a drug candidate for further development. Compound 28 is currently
      undergoing phase I and phase II clinical trials.

PMID- 19603810
TI  - Molecular behavior in small spaces.
AB  - The study of physical organic chemistry in solution is a mature science, over a
      century old, but over the last 10 years or so, reversible encapsulation has
      changed the way researchers view molecular interactions. It is now clear that the
      behavior of molecules in dilute solution is really quite different from their
      behavior in capsules. Molecules isolated from bulk media in spaces barely large
      enough to accommodate them and a few neighbors show new phenomena: their
      activities resemble those of molecules inside biochemical structures--pockets of
      enzymes, interiors of chaperones, or the inner space of the ribosome--rather than
      conventional behavior in solution. In this Account, we recount the behavior of
      molecules in these small spaces with emphasis on structures and reactivities that
      have not been, and perhaps cannot be, seen in conventional solution chemistry.
      The capsules self-assemble through a variety of forces, including hydrogen bonds,
      metal-ligand interactions, and hydrophobic effects. Their lifetimes range from
      milliseconds to hours, long enough for NMR spectroscopy to reveal what is going
      on inside. We describe one particular capsule, the elongated shape of which gives
      rise to many of the effects and unique phenomena. Molecular guests that are
      congruent to the space of the host can be tightly packed inside and show reduced
      mobilities such as rotation and translation within the capsule. These mobilities
      depend strongly on what else is encapsulated with them. We also relate how
      asymmetric spaces can be created inside the capsule by using a chiral guest. In
      contrast to the situation in dilute solution, where rapid exchange of solute
      partners and free molecular motion average out the steric and magnetic effects of
      chirality, the long lifetimes of the encounters in the capsules magnify the
      effects of an asymmetric environment. The capsule remains achiral, but the
      remaining space is chiral, and coencapsulated molecules respond in an amplified
      way. We probe the various regions of the capsule with guests of different shape.
      Primary acetylenes, the narrowest of functional groups, can access the tapered
      ends of the capsule that exclude functions as small as methyl groups. The shape
      of the capsule also has consequences for aromatic guests, gently bending some and
      straightening out others. Flexible structures such as normal alkanes can be
      compressed to fit within the capsule and conform to its shape. We obtain a
      measure of the internal pressure caused by the compressed guests by determining
      its effect on the motion of the capsule's components. These forces can also drive
      a spring-loaded device under the control of external acids and bases. We show
      that spacer elements can be added to give self-assembled capsules of increased
      complexity, with 15 or more molecules spontaneously coming together in the
      assembly. In addition, we analyze the behavior of gases, including the breakdown
      of ideal gas behavior, inside these capsules. The versatility of these capsule
      structures points to possible applications as nanoscale reaction chambers. The
      exploration of these confined spaces and of the molecules within them continues
      to open new frontiers.

PMID- 19603811
TI  - Effects of the formation of large physical clusters on the pressure of a fluid.
AB  - A group of highly mobile particles that exceed the mobility restrictions given by
      mutually attractive forces among particles cannot mix homogeneously at the
      microscopic level with a group of low-mobility particles; low-mobility particles
      that participate in physical cluster formation caused by mutually attractive
      forces among particles cooperate with high-mobility particles to give the fluid a
      specific structure. If the pair correlation function is given as the sum of a
      correlation function that depends on the contribution of particles participating
      in the physical cluster formation and a correlation function that involves the
      contribution of high-mobility particles not participating in the physical cluster
      formation, the behavior of partial contributions to the pressure estimated from
      the virial equation reveals cooperation generated between particles forming
      physical clusters and high-mobility particles. Moreover, the behavior of partial
      contributions to the pressure demonstrates that branches of large stabilized
      physical clusters can form three-dimensional cavities confining high-mobility
      particles. The formation of three-dimensional cavities allows a fluid to have a
      specific microscopic structure.

PMID- 19603812
TI  - Transferrin as a luminal target for negatively charged liposomes in the inflamed
      colonic mucosa.
AB  - The need for improved specificity in the local treatment of inflammatory bowel
      diseases (IBD) led us to use negatively charged liposomes to target the inflamed
      colonic epithelium. The purpose of the present study was to elucidate the cause
      for our previous observations that such liposomes accumulate, preferentially, in
      the inflamed mucosa of rats that were induced with experimental colitis,
      following luminal administration. Protein analysis (tandem mass spectrometry,
      verified by Western blot) of inflamed mucosal specimens, extracted at pH 3, 5 and
      7, revealed an increased expression of transferrin (TF) at pH 3. Histological
      examination indicated that the TF was located at the luminal side of the inflamed
      epithelium. Negatively charged (but not neutral) liposomes adhered to both
      commercial and mucosal TF at low pH, but not at neutral pH. Moreover,
      preincubation of negatively charged liposomes with TF profoundly attenuated their
      adherence to the inflamed mucosa of the rat colon. It is concluded that, at a low
      pH, typical of the colon lumen in ulcerative colitis, TF mediates specific
      mucoadhesion of negatively charged liposomes to the inflamed mucosa. This
      observation could be useful in the rational design of specific drug vehicles
      aimed at IBD therapy after luminal administration.

PMID- 19603813
TI  - Confocal nanoscanning, bead picking (CONA): PickoScreen microscopes for automated
      and quantitative screening of one-bead one-compound libraries.
AB  - Solid phase combinatorial chemistry provides fast and cost-effective access to
      large bead based libraries with compound numbers easily exceeding tens of
      thousands of compounds. Incubating one-bead one-compound library beads with
      fluorescently labeled target proteins and identifying and isolating the beads
      which contain a bound target protein, potentially represents one of the most
      powerful generic primary high throughput screening formats. On-bead screening
      (OBS) based on this detection principle can be carried out with limited
      automation. Often hit bead detection, i.e. recognizing beads with a fluorescently
      labeled protein bound to the compound on the bead, relies on eye-inspection under
      a wide-field microscope. Using low resolution detection techniques, the
      identification of hit beads and their ranking is limited by a low fluorescence
      signal intensity and varying levels of the library beads' autofluorescence. To
      exploit the full potential of an OBS process, reliable methods for both automated
      quantitative detection of hit beads and their subsequent isolation are needed. In
      a joint collaborative effort with Evotec Technologies (now Perkin-Elmer Cellular
      Technologies Germany GmbH), we have built two confocal bead scanner and picker
      platforms PS02 and a high-speed variant PS04 dedicated to automated high
      resolution OBS. The PS0X instruments combine fully automated confocal large area
      scanning of a bead monolayer at the bottom of standard MTP plates with
      semiautomated isolation of individual hit beads via hydraulic-driven picker
      capillaries. The quantification of fluorescence intensities with high spatial
      resolution in the equatorial plane of each bead allows for a reliable
      discrimination between entirely bright autofluorescent beads and real hit beads
      which exhibit an increased fluorescence signal at the outer few micrometers of
      the bead. The achieved screening speed of up to 200,000 bead assayed in less than
      7 h and the picking time of approximately 1 bead/min allow exploitation of one
      bead one-compound libraries with high sensitivity, accuracy, and speed.

PMID- 19603814
TI  - Unsymmetrical Fe(III)Co(II) and Ga(III)Co(II) complexes as chemical hydrolases:
      biomimetic models for purple acid phosphatases (PAPs).
AB  - The design and development of suitable biomimetic catalytic systems capable of
      mimicking the functional properties of enzymes continues to be a challenge for
      bioinorganic chemists. In this study, we report on the synthesis, X-ray
      structures, and physicochemical characterization of the novel isostructural
      [Fe(III)Co(II)(BPBPMP)(mu-OAc)(2)]ClO(4) (1) and [Ga(III)Co(II)(BPBPMP)(mu
      OAc)(2)]ClO(4) (2) complexes with the unsymmetrical dinucleating ligand
      H(2)BPBPMP (2-bis[{(2-pyridyl-methyl)-aminomethyl}-6-{(2-hydroxy-benzyl)-(2
      pyridyl-methyl)}-aminomethyl]-4-methylphenol). The previously reported complex
      [Fe(III)Zn(II)(BPBPMP)(mu-OAc)(2)]ClO(4) (3) was investigated here by electron
      paramagnetic resonance for comparison with such studies on 1 and 2. A magneto
      structural correlation between the exchange parameter J (cm(-1)) and the average
      bond lengh d (A) of the [Fe(III)-O-M(II)] structural unit for 1 and for related
      isostructural Fe(III)M(II) complexes using the correlation J = -10(7) exp(-6.8d)
      reveals that this parameter is the major factor that determines the degree of
      antiferromagnetic coupling in the series [(BPBPMP)Fe(III)(mu-OAc)(2)M(II)](+)
      (M(II) = Mn, Fe, Co, Ni) of complexes. Potentiometric and spectrophotometric
      titrations along with electronic absorption studies show that, in aqueous
      solution, complexes 1 and 2 generate the [(HO)M(III)(mu-OH)Co(II)(H(2)O)] complex
      as the catalytically active species in diester hydrolysis reactions. Kinetic
      studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate
      by 1 and 2 show Michaelis-Menten behavior, with 2 being 35% more active than 1.
      In combination with k(H)/k(D) isotope effects, the kinetic studies suggest a
      mechanism in which a terminal M(III)-bound hydroxide is the hydrolysis-initiating
      nucleophilic catalyst. In addition, the complexes show maximum catalytic activity
      in DNA hydrolysis near physiological pH. The modest reactivity difference between
      1 and 2 is consistent with the slightly increased nucleophilic character of the
      Ga(III)-OH terminal group in comparison to Fe(III)-OH in the dinuclear
      M(III)Co(II) species.

PMID- 19603815
TI  - Core-shell triangular bifrustums.
AB  - Au(core)-Ag(shell) triangular bifrustum nanocrystals were synthesized in aqueous
      solution using a seed-mediated approach. The formation of the Ag layer on the Au
      nanoprism seeds leads to structures with highly tunable dipole and quadrupole
      surface plasmon resonances. Discrete dipole approximation calculations show that
      it is the geometry of these novel structures rather than the addition of a new
      element that leads to the plasmon tunability. The structure and composition of
      these novel nanocrystals have been investigated by transmission electron
      microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and energy
      dispersive spectrometry.

PMID- 19603817
TI  - Systematic improvement in charge carrier mobility of air stable triarylamine
      copolymers.
AB  - The electrical performance of organic semiconducting polymers in field-effect
      transistor devices is now sufficient for initial low complexity circuit
      applications. To achieve high performance, either operation in an inert
      atmosphere or a hydrophobic surface treatment and annealing step is typically
      required. In this communication we report a strategy to prepare fully air stable,
      amorphous semiconducting polymers which can achieve charge carrier mobilities in
      the range of 0.04 cm(2)/(V s), remaining over a period of over 3 months in
      ambient conditions.

PMID- 19603816
TI  - Observation of NMR signals from proteins introduced into living mammalian cells
      by reversible membrane permeabilization using a pore-forming toxin, streptolysin
      O.
AB  - We have developed a new in-cell NMR method that is applicable to any type of cell
      and does not require target protein modification or specialized equipment. The
      stable-isotope-labeled target protein, thymosin beta4 (Tbeta4), was delivered to
      293F cells, which were permeabilized by a pore-forming toxin, streptolysin O, and
      resealed by Ca(2+) after Tbeta4 uptake. As a result, we successfully observed
      (1)H-(15)N HSQC signals originating from the Tbeta4, including those from the N
      terminal acetylation, which had occurred inside the cell as a post-translational
      modification.

PMID- 19603818
TI  - Isomerization polymerization of 4-alkylcyclopentenes catalyzed by Pd complexes:
      hydrocarbon polymers with isotactic-type stereochemistry and liquid-crystalline
      properties.
AB  - Isomerization polymerization of 4-alkylcyclopentenes catalyzed by Pd-diimine
      complexes produces the polymers with trans-1,3-disubstituted cyclopentane rings
      located regularly along the polymer chain. The polymers with isotactic structure
      formed by using a C(2)-symmetric catalyst exhibited liquid-crystalline
      properties.

PMID- 19603819
TI  - Selective radical addition with a designed heterobifunctional halide: a primary
      study toward sequence-controlled polymerization upon template effect.
AB  - A ruthenium(II)-catalyzed, highly selective, quantitative radical addition of an
      alkene, methacrylic acid (MAA), has been achieved by using a template halide (2)
      containing a built-in amine group as a recognition site for the carboxyl group of
      the substrate. The specific ionic binding of MAA by the amine template (1:1 molar
      ratio) led to preferential formation of the 1:1 MAA-2 adduct, whereas a similar
      halide without a template induced MAA oligomerization even in the presence of an
      externally added amine. A competitive radical addition of MAA versus its ester
      form [methyl methacrylate (MMA)] on the halide further demonstrated that the
      substrate selectivity [k'(MAA)/k'(MMA)] for 2 is enhanced more than 10 times by
      the intramolecular introduction of the template relative to the result for the
      nontemplate halide. These specificities are most likely triggered by the specific
      interaction (recognition) of the carboxyl group in MAA via the acid-selective
      template amine, which is implanted in the close vicinity of the radical addition
      site in 2. These results intimate possibility of control over the repeat-unit
      sequence in precision polymerization.

PMID- 19603821
TI  - Concerning the hydrolytic stability of 8-aryl-2'-deoxyguanosine nucleoside
      adducts: implications for abasic site formation at physiological pH.
AB  - Direct addition of aryl radical species to the C(8)-site of 2'-deoxyguanosine
      (dG) affords C(8)-aryl-dG adducts that are produced by carcinogenic
      arylhydrazines, polycyclic aromatic hydrocarbons (PAHs), and certain phenolic
      toxins. A common property of C(8)-arylpurine adduction is the accompaniment of
      abasic site formation. To determine how the C(8)-aryl moiety contributes to sugar
      loss, UV-vis spectroscopy has been employed to determine N(7) pK(a1) values and
      hydrolysis kinetics, while density functional theory (DFT) calculations have been
      utilized to probe the structural features and stability of the C(8)-aryl-dG
      adducts bearing different para and ortho substituents. In all cases, the C(8)
      aryl-dG adducts adopt a syn conformation containing a strong O(5)'-H...N(3)
      hydrogen bond with the aryl ring twisted with respect to the nucleobase. The
      adducts undergo N(7)-protonation with ionization constants and calculated N(7)
      proton affinity (PA) values similar to those measured for dG. The hydrolysis
      kinetics shows that C(8)-aryl-dG nucleoside adducts are more prone than dG to
      acid-catalyzed hydrolysis, with those bearing para substituents having k(1)
      values that are ca. 90- to 200-fold larger than k(1) for dG, while the effects
      for the ortho adducts are only ca. 9- to 60-fold larger. Changes in the rate of
      hydrolysis are further explained by calculations showing that glycosidic bond
      cleavage in the syn orientation of both neutral and N(7)-protonated dG has a
      lower barrier than the anti orientation, and the bulky (phenyl) group further
      decreases the barrier. Despite adduct reactivity in acidic media, all adducts are
      relatively stable at physiological pH with t(1/2) approximately 25 days,
      suggesting that they are unlikely intermediates leading to abasic site formation
      at physiological pH. This information has allowed development of a new rationale
      for the tendency of abasic site formation to accompany C(8)-arylpurine adduction
      within duplex DNA at neutral pH.

PMID- 19603822
TI  - Spectroscopic identification of amyl alcohol hydrates through free OH
      observation.
AB  - In this study, we identify the crystal structures of amyl alcohol + CH(4)
      hydrates and demonstrate that the free OH observation of alcohol hydrates
      provides evidence of OH incorporation into the host framework occurring in some
      amyl alcohols. While two amyl alcohols, 3-methyl-2-butanol and 2-methyl-2
      butanol, were identified as encaged in the 5(12)6(8) large cage of structure-H
      hydrate, as expected from their molecular sizes above 7.5 A, two other amyl
      alcohols, 3-methyl-1-butanol and 2,2-dimethyl-1-propanol, were identified to be
      abnormally included in the 5(12)6(4) large cage of structure-II hydrate in spite
      of their too large sizes of 9.04 and 7.76 A, respectively. The Raman spectra of
      two "normal" amyl alcohol hydrates evolved free OH peaks around 3,600 cm(-1),
      implying that there is no strong hydrogen bonding interaction between alcohol
      guest and water host; however, for two "abnormal" amyl alcohol hydrates, the
      corresponding peaks were not detected, which indicates that the OH is
      incorporated into the host lattice in order to make the large alcohol guest fit
      into the relatively small 5(12)6(4) cage of structure-II. The present findings
      are expected to provide useful information for a better understanding of alcohol
      guest dynamic behavior that might be significantly affected by structural
      dimensions and host-guest interactions.

PMID- 19603820
TI  - Exploring symmetry-based logic for a synthesis of palau'amine.
AB  - A synthetic approach to palau'amine is described that exploits veiled symmetry in
      the structure. Bis-alkylidenes i have been prepared and found susceptible to
      halogenative desymmetrization using t-BuOCl. This oxidation forms the imbedded
      spirocyclopentane motif observed in the natural product. A host of atypical
      reactions and processes developed during these studies are discussed, as are
      plans for completing total syntheses of this compound class.

PMID- 19603823
TI  - Topological defects and shape of aromatic self-assembled vesicles.
AB  - We show that the stacking of flat aromatic molecules on a curved surface results
      in topological defects. We consider, as an example, spherical vesicles, self
      assembled from molecules with 5- and 6-thiophene cores. We predict that the
      symmetry of the molecules influences the number of topological defects and the
      resulting equilibrium shape.

PMID- 19603824
TI  - Prediction of enzyme classes from 3D structure: a general model and examples of
      experimental-theoretic scoring of peptide mass fingerprints of Leishmania
      proteins.
AB  - The number of protein and peptide structures included in Protein Data Bank (PDB)
      and Gen Bank without functional annotation has increased. Consequently, there is
      a high demand for theoretical models to predict these functions. Here, we trained
      and validated, with an external set, a Markov Chain Model (MCM) that classifies
      proteins by their possible mechanism of action according to Enzyme Classification
      (EC) number. The methodology proposed is essentially new, and enables prediction
      of all EC classes with a single equation without the need for an equation for
      each class or nonlinear models with multiple outputs. In addition, the model may
      be used to predict whether one peptide presents a positive or negative
      contribution of the activity of the same EC class. The model predicts the first
      EC number for 106 out of 151 (70.2%) oxidoreductases, 178/178 (100%)
      transferases, 223/223 (100%) hydrolases, 64/85 (75.3%) lyases, 74/74 (100%)
      isomerases, and 100/100 (100%) ligases, as well as 745/811 (91.9%) nonenzymes. It
      is important to underline that this method may help us predict new enzyme
      proteins or select peptide candidates that improve enzyme activity, which may be
      of interest for the prediction of new drugs or drug targets. To illustrate the
      model's application, we report the 2D-Electrophoresis (2DE) isolation from
      Leishmania infantum as well as MADLI TOF Mass Spectra characterization and
      theoretical study of the Peptide Mass Fingerprints (PMFs) of a new protein
      sequence. The theoretical study focused on MASCOT, BLAST alignment, and alignment
      free QSAR prediction of the contribution of 29 peptides found in the PMF of the
      new protein to specific enzyme action. This combined strategy may be used to
      identify and predict peptides of prokaryote and eukaryote parasites and their
      hosts as well as other superior organisms, which may be of interest in drug
      development or target identification.

PMID- 19603825
TI  - Correlation between y-type ions observed in ion trap and triple quadrupole mass
      spectrometers.
AB  - Multiple reaction monitoring mass spectrometry (MRM-MS) is a technique for high
      sensitivity targeted analysis. In proteomics, MRM-MS can be used to monitor and
      quantify a peptide based on the production of expected fragment peaks from the
      selected peptide precursor ion. The choice of which fragment ions to monitor in
      order to achieve maximum sensitivity in MRM-MS can potentially be guided by
      existing MS/MS spectra. However, because the majority of discovery experiments
      are performed on ion trap platforms, there is concern in the field regarding the
      generalizability of these spectra to MRM-MS on a triple quadrupole instrument. In
      light of this concern, many operators perform an optimization step to determine
      the most intense fragments for a target peptide on a triple quadrupole mass
      spectrometer. We have addressed this issue by targeting, on a triple quadrupole,
      the top six y-ion peaks from ion trap-derived consensus library spectra for 258
      doubly charged peptides from three different sample sets and quantifying the
      observed elution curves. This analysis revealed a strong correlation between the
      y-ion peak rank order and relative intensity across platforms. This suggests that
      y-type ions obtained from ion trap-based library spectra are well-suited for
      generating MRM-MS assays for triple quadrupoles and that optimization is not
      required for each target peptide.

PMID- 19603826
TI  - Quantification of protein expression changes in the aging left ventricle of
      Rattus norvegicus.
AB  - As the heart ages, electrophysiological and biochemical changes can occur, and
      the ventricle in many cases loses distensibility, impairing diastolic function.
      How the proteomic signature of the aged ventricle is unique in comparison to
      young hearts is still under active investigation. We have undertaken a
      quantitative proteomics study of aging left ventricles (LVs) utilizing the
      isobaric Tagging for Relative and Absolute Quantification (iTRAQ) methodology.
      Differential protein expression was observed for 117 proteins including proteins
      involved in cell signaling, the immune response, structural proteins, and
      proteins mediating responses to oxidative stress. For many of these proteins,
      this is the first report of an association with the aged myocardium.
      Additionally, two proteins of unknown function were identified. This work serves
      as the basis for making future comparisons of the aged left ventricle proteome to
      that of left ventricles obtained from other models of disease and heart failure.

PMID- 19603827
TI  - Reanalysis of Tyrannosaurus rex Mass Spectra.
AB  - Asara et al. reported the detection of collagen peptides in a 68-million-year-old
      Tyrannosaurus rex bone by shotgun proteomics. This finding has been called into
      question as a possible statistical artifact. We reanalyze Asara et al.'s tandem
      mass spectra using a different search engine and different statistical tools. Our
      reanalysis shows a sample containing common laboratory contaminants, soil
      bacteria, and bird-like hemoglobin and collagen.

PMID- 19603828
TI  - Proteomic expression profiling and identification of serum proteins using
      immobilized trypsin beads with MALDI-TOF/TOF.
AB  - MALDI-TOF mass spectrometry is a widely used technique for serum protein
      expression profiling and biomarker discovery. Many profiling strategies typically
      employ chemical affinity beads or surfaces to decrease sample complexity of
      dynamic fluids such as serum or plasma. However, many of the proteins captured on
      a particular surface or bead are not resolved in the lower mass ranges where time
      of-flight mass spectrometers are most effective. Thus, a majority of reported
      protein expression profiling studies primarily interrogate the native low
      molecular mass constituents of the target sample. We report an expression
      profiling workflow that utilizes immobilized trypsin paramagnetic beads following
      an initial affinity bead fractionation step, thereby reducing large mass proteins
      to peptides that are better suited to analysis and sequencing determinations. Our
      bead-based trypsin approach resulted in more efficient digestion of complex serum
      protein extracts at short incubation times. This method was reproducible and
      readily adaptable to robotic sample handling and may be combined in tandem with
      other bead fractionation surfaces. When weak cationic and weak anionic bead
      surfaces were used, experimental conditions were optimized for tandem
      combinations of these beads with the immobilized trypsin step to produce an
      efficient serum fractionation strategy. A proof-of-concept pilot experiment using
      pooled human serum samples demonstrating reproducibility is presented, along with
      the sequence determination of selected tryptic peptides of serum proteins.

PMID- 19603829
TI  - MaRiMba: a software application for spectral library-based MRM transition list
      assembly.
AB  - Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis
      method that has been increasingly viewed as an avenue to explore proteomes with
      unprecedented sensitivity and throughput. We have developed a software tool,
      called MaRiMba, to automate the creation of explicitly defined MRM transition
      lists required to program triple quadrupole mass spectrometers in such analyses.
      MaRiMba creates MRM transition lists from downloaded or custom-built spectral
      libraries, restricts output to specified proteins or peptides, and filters based
      on precursor peptide and product ion properties. MaRiMba can also create MRM
      lists containing corresponding transitions for isotopically heavy peptides, for
      which the precursor and product ions are adjusted according to user
      specifications. This open-source application is operated through a graphical user
      interface incorporated into the Trans-Proteomic Pipeline, and it outputs the
      final MRM list to a text file for upload to MS instruments. To illustrate the use
      of MaRiMba, we used the tool to design and execute an MRM-MS experiment in which
      we targeted the proteins of a well-defined and previously published standard
      mixture.

PMID- 19603830
TI  - Amyloid fibrillation of human Apaf-1 CARD.
AB  - The idea of establishing the amyloid-like fibrillation tendency of pro- and
      antisurvival proteins of human apoptotic pathways is relevant for delineating the
      conditions that lead to aberrant differentiation, development, and tissue
      homeostasis. As the first step in this direction, we report here that the caspase
      recruitment domain (CARD) of recombinant human apoptotic protease activating
      factor-1 (Apaf-1) can be induced to undergo amyloid-like fibrillation. The study
      was initiated with a set of biophysical investigations into the possibility and
      in vitro conditions for fibril growth. By scanning the pH-induced conformational
      transitions, protein stability, and stopped-flow folding-unfolding kinetics, we
      detected a molten globule (MG) transition of the CARD at pH <4. In a bid to
      reduce the surface-accessible hydrophobic patches in the MG state, the CARD
      monomer undergoes self-association to produce soluble oligomers that serve as
      precursor aggregates for protofibril formation. The monomer-to-oligomer self
      association process is akin to the well-known homophilic CARD-CARD interaction by
      which CARDs of the same or different apoptotic proteins associate to transduce
      and regulate the apoptotic signal. The fibrillation reaction of the Apaf-1 CARD
      was conducted at pH 2.1 and 60 degrees C, because reduction of exposed
      hydrophobic surfaces in the MG state is more favored under the moderated solution
      condition. The Gaussian distributions of diameters of the fibril population
      suggest values of 2.1 and 2.7 nm for the mean diameter of precursor aggregates
      and protofibrils or elongated fibrils, respectively.

PMID- 19603831
TI  - Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of
      arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid.
AB  - Ibuprofen and mefenamic acid are weak, competitive inhibitors of cyclooxygenase-2
      (COX-2) oxygenation of arachidonic acid (AA) but potent, noncompetitive
      inhibitors of 2-arachidonoylglycerol (2-AG) oxygenation. The slow, tight-binding
      inhibitor, indomethacin, is a potent inhibitor of 2-AG and AA oxygenation whereas
      the rapidly reversible inhibitor, 2'-des-methylindomethacin, is a potent
      inhibitor of 2-AG oxygenation but a poor inhibitor of AA oxygenation. These
      observations are consistent with a model in which inhibitors bind in one subunit
      of COX-2 and inhibit 2-AG binding in the other subunit of the homodimeric
      protein. In contrast, ibuprofen and mefenamate must bind in both subunits to
      inhibit AA binding.

PMID- 19603832
TI  - The immobilization of gossypol derivative on N-polyvinylpyrrolidone increases its
      water solubility and modifies membrane-active properties.
AB  - The conjugate of the gossypol derivative megosin (1) with N-polyvinylpyrrolidone
      named rometin (2) was synthesized. The effects of 1 and 2 on the structure and
      permeability of human erythrocytes and rat liver mitochondria were compared.
      Compound 1 induced dose-dependent erythrocyte hemolysis and increased
      mitochondrial permeability, with concomitant changes in membrane structure as
      determined by ESR and fluorescence anisotropy methods. Immobilization of 1 on N
      polyvinylpyrrolidone (compound 2) increased its water solubility and reduced the
      intensity of its effects on erythrocyte membrane integrity and mitochondrial
      permeability, which correlated with a decrease in the membranes structural
      changes induced by the compound. Although the same concentrations of free and N
      polyvinylpyrrolidone bound 1 were used, far less (14)C-labeled 1 was incorporated
      into the membranes from complex than free 1. The increase in water solubility and
      the reduction of membrane-active properties of 1 after immobilization on N
      polyvinylpyrrolidone could explain our previous observation of the decreased
      toxicity of 1.

PMID- 19603833
TI  - In silico prediction of volume of distribution in human using linear and
      nonlinear models on a 669 compound data set.
AB  - The prediction of human pharmacokinetics early in the drug discovery cycle has
      become of paramount importance, aiding candidate selection and benefit-risk
      assessment. We present herein computational models to predict human volume of
      distribution at steady state (VD(ss)) entirely from in silico structural
      descriptors. Using both linear and nonlinear statistical techniques, partial
      least-squares (PLS), and random forest (RF) modeling, a data set of human VD(ss)
      values for 669 drug compounds recently published ( Drug Metab. Disp. 2008 , 36 ,
      1385 - 1405 ) was explored. Descriptors covering 2D and 3D molecular topology,
      electronics, and physical properties were calculated using MOE and Volsurf+.
      Model evaluation was accomplished using a leave-class-out approach on nine
      therapeutic or structural classes. The models were assessed using an external
      test set of 29 additional compounds. Our analysis generated models, both via a
      single method or consensus which were able to predict human VD(ss) within
      geometric mean 2-fold error, a predictive accuracy considered good even for more
      resource-intensive approaches such as those requiring data generated from studies
      in multiple animal species.

PMID- 19603834
TI  - Imaging and estimating the surface heterogeneity on a droplet containing
      cosolvents.
AB  - Cosolvents have numerous applications in many industries as well as scientific
      research. The shortage in the knowledge of the structures in a cosolvent system
      is significant. In this work, we display the spatial as well as the kinetic
      distribution of the cosolvents using droplets as paradigms. When an alcohol/water
      containing sessile droplet evaporates on a substrate, it phase segregates into a
      water-enriched core and a thin alcohol prevailing shell. This is considered to be
      due to the different escaping rate of solvents out of the liquid-vapor (l-v)
      interfaces. In between the core and shell phases, there exists a rough and solid
      like liquid-liquid (l-l) wall interface as marked by the fluorescent polystyrene
      spheres and imaged by a confocal microscope. Holes and patches of beads are
      observed to form on this phase boundary. The water-dispersed beads prefer to
      partition within the core. The shell prevails in the droplet during most of the
      drying and shrinks with the l-v boundary. By monitoring the morphological
      progression of the droplet, the composition of the cosolvent at the liquid-vapor
      interface is obtained.

PMID- 19603835
TI  - Motion of single terrylene molecules in confined channels of poly(butadiene)
      poly(ethylene oxide) diblock copolymer.
AB  - The motion of terrylene probe molecules in confined PB channels of an asymmetric
      PB-PEO diblock copolymer has been investigated by single molecule tracking. The
      one-dimensional diffusion coefficients were found to be significantly smaller and
      had a narrower distribution compared to two-dimensional diffusion coefficients in
      PB. The trajectories of some single molecules showed unusual behavior of directed
      motion where mean square displacement had a parabolic dependence on lag time. The
      likely origin of this behavior is discussed in terms of local variations in the
      PB channel width and the resulting change in the local density. The results show
      the effect of nonuniformities and heterogeneities in the channels on the motion
      of single molecules and demonstrate the sensitivity of single molecule tracking
      in characterizing self-assembled block copolymer morphologies.

PMID- 19603836
TI  - Sorption of CO2 and a CO2 compatible salt into an extreme ultraviolet photoresist
      film on a SiO2 substrate.
AB  - The development of standard extreme ultraviolet (EUV) lithography photoresists
      with a CO2 compatible salt (CCS) and supercritical carbon dioxide (scCO2)
      solution has several advantages over typical trimethylammonium hydroxide
      development, including reduced image collapse and line width roughness in the
      resulting microchip features. The mechanism and characteristics of the CCS/scCO2
      development process are currently being examined. In this paper, the sorption
      behavior of CO2 and the CCS onto a bare SiO2 surface and into the photoresist was
      studied using a quartz crystal microbalance (QCM). From the adsorption studies of
      CO2 and CCS/CO2 onto a bare SiO2 surface, it was found that the CCS begins to
      adsorb at 8.0 MPa at a temperature of 35 degrees C and at 9.4 MPa at a
      temperature of 50 degrees C. The adsorption of the CCS was favored and driven by
      entropy changes. The absorption of CO2 into the glassy photoresist resin was also
      measured with QCM and found comparable to CO2 absorption in glassy polystyrene
      for 35 and 50 degrees C up to a pressure where the photoresist is believed to
      dewet from the substrate. The diffusion behavior during CO2 absorption was found
      to be comparable to that of small fluorescent molecule diffusion in a CO2 swollen
      polystyrene.

PMID- 19603837
TI  - Optical spectra and stokes shift in double-stranded helical supramolecular
      assemblies.
AB  - We study the photoluminescence from helical MOPV4 aggregates using a model that
      includes excitonic coupling, exciton-phonon coupling, and spatially correlated
      disorder in the chromophore transition energies. The helical aggregates consist
      of stacked dimers of MOPV4 chromophores. We have modeled these helical stacks as
      double-stranded aggregates, allowing us to investigate the effect of correlated
      disorder within the dimers on emission. We have studied the dependence of the
      Stokes shift, the emission line widths, and the ratio of the 0-0 to 0-1 emission
      peaks on the aggregate size and disorder. Our findings show that this peak ratio
      is quite insensitive to the aggregate size if the latter exceeds the coherence
      length of the emitting exciton. This makes this ratio a reliable probe for both
      disorder and the coherence length of the emitting exciton. We have found only a
      weak dependence of this peak ratio on the degree of correlation between the
      transition energies within each dimer, whereas such correlation has a large
      effect on the aggregate-size-dependent Stokes shift. By comparison with
      experiment, we have estimated the coherence length of the emitting exciton to be
      only one lattice spacing along the stacking direction. From our analysis of the
      Stokes shift we conclude that the exciton diffusion length is in the range 6-13
      nm.

PMID- 19603838
TI  - Electrospinning fabrication of high strength and toughness polyimide nanofiber
      membranes containing multiwalled carbon nanotubes.
AB  - Polyimide (PI) and PI nanocomposite fibers containing different amounts of
      multiwalled carbon nanotubes (MWNTs) were produced for the first time by
      electrospinning. The membranes prepared were composed of highly aligned
      nanofibers and showed significant enhancement in mechanical properties, compared
      with the membranes prepared by conventional solution-casting method. Surface
      functionalized MWNTs were homogeneously dispersed and highly aligned along the
      fiber axis, whereas most of the pristine MWNTs formed aggregates or bundles and
      even protruded out of the electrospun nanofibers. The thermal and mechanical
      properties of polyimide matrix were significantly improved with the incorporation
      of MWNTs. And the elongation at break of the nanofiber membranes can reach 100%
      for the nanotube loading level of 3.5 wt %. It was found that electrospinning the
      in situ prepared MWNT/poly(amic acid) solution can achieve better polymer chain
      orientation and thus better mechanical properties of the as-prepared membranes.
      Our study demonstrates a good example for the preparation of high-performance
      polymer/carbon nanotube nanocomposites by using electrospinning.

PMID- 19603839
TI  - Structure and stability of (alpha-CD)3 aggregate and OEG@(alpha-CD)3
      pseudorotaxane in aqueous solution: a molecular dynamics study.
AB  - Empty linear associations accounting for three alpha-CD units and their
      corresponding pseudorotaxanes have been studied by means of long length molecular
      dynamics (MD) simulations in a vacuum and in aqueous solution. Results from MD
      for empty sequences lead to a quite stable arrangement formed by three mutually
      perpendicular cyclodextrin (CD) units named here as 3P. In such a spatial
      arrangement, the van der Waals term in the force field is pronounced, accounting
      for almost 40% of the association energy, which ensures the noticeable stability
      of the 3P association even in aqueous media. In addition, it can be stated that
      only the presence of the oligomer forces the CD units to acquire an almost linear
      association. Mutually perpendicular-based arrangements are the most favorable
      spatial disposition in aqueous media. We believe this work is the first step
      toward a more ambitious study including very large CD sequences, aiming to
      understand the association process in aqueous solution at a molecular level.

PMID- 19603840
TI  - The effect of postadded ethylene glycol surfactants on DNA-cationic
      surfactant/water mesophases.
AB  - The addition of amphiphiles grafted with polyethylene glycol units to constructs
      of DNA-amphiphiles is of most relevance for applications demanding colloidal
      stability. In this work, we study the self-assembly behavior of a true ternary
      mixture comprising (i) an electroneutral complex of DNA and a cationic surfactant
      (dodecyltrimethylammonium, DTA), (ii) water, and (iii) nonionic surfactant
      (dodecyl tetraethylene glycol, C12EO4; and dodecyl octaethylene glycol, C12EO8).
      The phase diagrams of the two systems: DNA-DTA/C12EO4/water and DNA
      DTA/C12EO8/water were carried out using 2H NMR, and small-angle X-ray scattering
      (SAXS). In both mixtures, the DNA-DTA complex incorporates the postadded nonionic
      surfactant and large liquid crystalline regions were found. The supramolecular
      assemblies evolve from a 2D hexagonal structure of the normal type to a lamellar
      phase as the content of nonionic surfactant is increased. The effect of ethylene
      glycol unit size in the phase behavior is discussed. We suggest that when longer
      ethylene glycol units (C12EO8 vs C12EO4) are used, the DNA-DTA aggregate gets
      saturated with the nonionic surfactant and there exists a coexistence of a fully
      swollen mesophase phase of C12EO8 alone presumably of the normal hexagonal type
      with the lamellar and hexagonal phases of DNA-DTA/C12EO8/water.

PMID- 19603841
TI  - Multiple conformation transitions of triple helical lentinan in DMSO/water by
      microcalorimetry.
AB  - The hydrogen bonding interactions of the triple helical lentinan, beta-(1-->3)-D
      glucan from Lentinus edodes, in the mixtures of dimethyl sulfoxide (DMSO) and
      water were investigated by light scattering, viscometry, and ultrasensitive
      differential scanning calorimetry (US-DSC). The results revealed that two
      conformation transitions occurred in the lentinan solution with an increase of
      temperature. A reversible transition from triple helix I to triple helix II,
      namely, from a high degree of immobilization of the backbone to a more freely
      rotating one, occurred in the temperature range from 8 to 45 degrees C. The other
      was an irreversible conformation transition from triple helix to single strand
      flexible chain at 90-140 degrees C, depending on the DMSO concentration. The side
      chain of the triple helix I lentinan combined with water clusters through
      hydrogen bonds to form an associating water layer in the first region, leading to
      a high degree of immobilization of the backbone. However, the side chain could
      rotate in triple helix II at slightly elevated temperature, as a result of the
      breaking of the associating structure with relatively lower energy. The second
      transition resulted from the destruction of the intra- and intermolecular
      hydrogen bonds in lentinan, which sustain the triple helical structure.
      Furthermore, the transition in the high temperature region showed high
      cooperation, suggesting that the intra- and intermolecular hydrogen bonds with
      the relatively high energy were destructed simultaneously. Therefore, the
      diversity of the hydrogen bonds created the multiple conformational transitions
      of the triple helical polysaccharide in the aqueous solution.

PMID- 19603843
TI  - Role of quantum coherence and environmental fluctuations in chromophoric energy
      transport.
AB  - The role of quantum coherence in the dynamics of photosynthetic energy transfer
      in chromophoric complexes is not fully understood. In this work, we quantify the
      biological importance of fundamental physical processes, such as the excitonic
      Hamiltonian evolution and phonon-induced decoherence, by their contribution to
      the efficiency of the primary photosynthetic event. We study the effect of
      spatial correlations in the phonon bath and slow protein scaffold movements on
      the efficiency and the contributing processes. To this end, we develop two
      theoretical approaches based on a Green's function method and energy transfer
      susceptibilities. We investigate the Fenna-Matthews-Olson protein complex, in
      which we find a contribution of coherent dynamics of about 10% in the presence of
      uncorrelated phonons and about 30% in the presence of realistically correlated
      ones.

PMID- 19603842
TI  - Magnesium-induced lipid bilayer microdomain reorganizations: implications for
      membrane fusion.
AB  - Interactions between dipalmitoylphosphatidylcholine (DPPC) and
      dipalmitoylphosphatidylserine (DPPS), combined both as binary lipid bilayer
      assemblies and separately, under the influence of divalent Mg2+, a membrane
      bilayer fusogenic agent, are reported. Infrared vibrational spectroscopic
      analyses of the lipid acyl chain methylene symmetric stretching modes indicate
      that aggregates of the two phospholipid components exist as domains
      heterogeneously distributed throughout the binary bilayer system. In the presence
      of Mg2+, DPPS maintains an ordered orthorhombic subcell gel phase structure
      through the phase transition temperature, while the DPPC component is only
      minimally perturbed with respect to the gel to liquid crystalline phase change.
      The addition of Mg2+ induces a reorganization of the lipid domains in which the
      gel phase acyl chain planes rearrange from a hexagonal configuration toward a
      triclinic, parallel chain subcell. Examination of the acyl chain methylene
      deformation modes at low temperatures allows a determination of DPPS microdomain
      sizes, which decrease upon the addition of DPPC-d62 in the absence of Mg2+. On
      adding Mg2+, a uniform DPPS domain size is observed in the binary mixtures. In
      either the presence or absence of Mg2+, DPPC-d62 aggregates remain in a
      configuration for which microdomain sizes are not spectroscopically measurable.
      Analysis of the acyl chain methylene deformation modes for DPPC-d62 in the binary
      system suggests that clusters of the deuterated lipids are distributed throughout
      the DPPS matrix. Light scattering and fluorescence measurements indicate that
      Mg2+ induces both the aggregation and the fusion of the lipid assemblies as a
      function of the ratio of DPPS to DPPC. The structural reorganizations of the
      lipid microdomains within the DPPS-DPPC bilayer are interpreted in the context of
      current concepts regarding lipid bilayer fusion.

PMID- 19603844
TI  - Protonated arginine and protonated lysine: hydration and its effect on the
      stability of salt-bridge structures.
AB  - Using a mass spectrometer equipped with a drift cell, water binding energies of
      protonated arginine (ArgH+) and protonated lysine (LysH+) were determined in
      equilibrium experiments and supplementary calculations at the B3LYP/6-311++G**
      level of theory. The binding energy of the first water molecule was measured to
      be 10.3 and 10.9 kcal/mol for ArgH+ and LysH+, respectively. Water binding
      energies decrease with increasing degree of hydration reaching values of 6-7
      kcal/mol for the fourth and fifth water molecule. Theory reproduces this trend of
      decreasing binding energies correctly and theoretical water binding energies
      agree with experiment quantitatively within 2 kcal/mol. Lowest-energy theoretical
      structures of ArgH+ and LysH+ are characterized by protonated side chains and
      neutral alpha-amino and carboxyl groups which form intramolecular hydrogen bonds
      to the ionic group (charge solvation or CS structures). The salt bridge (SB)
      structures with two cationic groups (side chain and alpha-amine) and one anionic
      group (carboxyl) are 13.1 and 9.3 kcal/mol higher in energy for ArgH+ and LysH+,
      respectively. Theory indicated that the first water molecule binds to the ionic
      group of the CS structures of ArgH+ and LysH+. With increasing degree of
      hydration intramolecular interactions are replaced one by one with water bridges
      with water inserted into the intramolecular hydrogen bonds. Whereas the global
      minima of ArgH+.(H2O)n and LysH+.(H2O)n, n<7, were calculated to represent CS
      structures, 7-fold hydrated CS and SB structures, ArgH+.(H2O)7 and LysH+.(H2O)7,
      are nearly isoenergetic (within <1 kcal/mol).

PMID- 19603845
TI  - Damage induced to DNA by low-energy (0-30 eV) electrons under vacuum and
      atmospheric conditions.
AB  - In this study, we show that it is possible to obtain data on DNA damage induced
      by low-energy (0-30 eV) electrons under atmospheric conditions. Five monolayer
      films of plasmid DNA (3197 base pairs) deposited on glass and gold substrates are
      irradiated with 1.5 keV X-rays in ultrahigh vacuum and under atmospheric
      conditions. The total damage is analyzed by agarose gel electrophoresis. The
      damage produced on the glass substrate is attributed to energy absorption from X
      rays, whereas that produced on the gold substrate arises from energy absorption
      from both the X-ray beam and secondary electrons emitted from the gold surface.
      By analysis of the energy of these secondary electrons, 96% are found to have
      energies below 30 eV with a distribution peaking at 1.4 eV. The differences in
      damage yields recorded with the gold and glass substrates is therefore
      essentially attributed to the interaction of low-energy electrons with DNA under
      vacuum and hydrated conditions. From these results, the G values for low-energy
      electrons are determined to be four and six strand breaks per 100 eV,
      respectively.

PMID- 19603846
TI  - 13C and 15N NMR study of the hydration response of T4 lysozyme and alphaB
      crystallin internal dynamics.
AB  - The response to hydration of the internal protein dynamics was studied by the
      means of solid state NMR relaxation and magic angle spinning exchange techniques.
      Two proteins, lysozyme from bacteriophage T4 and human alphaB-crystallin were
      used as exemplars. The relaxation rates R1 and R1rho of 13C and 15N nuclei were
      measured as a function of a hydration level of the proteins in the range 0-0.6 g
      of water/g of protein. Both proteins were totally 15N-enriched with natural 13C
      abundance. The relaxation rates were measured for different spectral bands
      (peaks) that enabled the characterization of the dynamics separately for the
      backbone, side chains, and CH3 and NH3+ groups. The data obtained allowed a
      comparative analysis of the hydration response of the protein dynamics in
      different frequency ranges and different sites in the protein for two different
      proteins and two magnetic nuclei. The most important result is a demonstration of
      a qualitatively different response to hydration of the internal dynamics in
      different frequency ranges. The amplitude of the fast (nanosecond time scale)
      motion gradually increases with increasing hydration, whereas that of the slow
      (microsecond time scale) motion increases only until the hydration level 0.2-0.3
      g of water/g of protein and then shows almost no hydration dependence. The reason
      for such a difference is discussed in terms of the different physical natures of
      these two dynamic processes. Backbone and side chain nuclei show the same
      features of the response of dynamics with hydration despite the fact that the
      backbone motional amplitudes are much smaller than those of side chains. Although
      T4 lysozyme and alphaB-crystallin possess rather different structural and
      biochemical properties, both proteins show qualitatively very similar hydration
      responses. In addition to the internal motions, exchange NMR data enabled the
      identification of one more type of motion in the millisecond to second time scale
      that appears only at high hydration levels. This motion was attributed to the
      restricted librations of the protein as a whole.

PMID- 19603847
TI  - Closure duration analysis of incomplete stop consonants due to stop-stop
      interaction.
AB  - An incomplete stop consonant is characterized either by an indistinguishable
      closure or a missing burst. If an incomplete stop happens due to a stop following
      another stop [stop-stop interaction (SSI)], its acoustics typically resemble that
      of a complete stop-one closure followed by a single burst. As a consequence, stop
      detectors would fail to distinguish an SSI from a complete stop. Analysis of the
      TIMIT corpus shows 35.04% incomplete stops (14.97% SSI). It is shown that by
      using automatically estimated (and hand-labeled) closure duration, complete stops
      can be distinguished from incomplete stops due to SSI with 69.66% (79.14%)
      accuracy.

PMID- 19603848
TI  - Time-domain Kirchhoff model for acoustic scattering from an impedance polygon
      facet.
AB  - Kirchhoff formula for an impedance polygon facet is given in the time domain. The
      derived formula is expressed as a summation of the transient analytic functions
      and generalized functions and represents an impulse response of the impedance
      polygon facet. Current formula can be applied to transient scattering analysis of
      underwater objects such as fish and submarine, or rough surface in the
      geometrical scattering region.

PMID- 19603849
TI  - Scaled model experiment of long-range across-slope pulse propagation in a
      penetrable wedge.
AB  - In this paper, laboratory scale measurements of long-range across-slope
      propagation of broadband pulses in a shallow-water wedge-shaped environment with
      a sandy bottom are reported. The scaled model was designed to study the three
      dimensional (3D) acoustic field in the presence of only a few propagating modes.
      The recorded time series exhibit prominent 3D effects such as mode shadow zones
      and multiple mode arrivals. Inspection of the spectral content of the time
      signals gives evidence of intra-mode interference and frequency dependence of the
      mode cut-off range in the across-slope direction.

PMID- 19603850
TI  - High frequency measurements of sound speed and attenuation in water-saturated
      glass-beads of varying size.
AB  - Acoustic measurements of p-wave speed and attenuation were made for water
      saturated granular medium, consisting of six kinds of glass-beads with mean grain
      size ranging from 90 to 875 microm, at frequency range between 400 kHz and 1.1
      MHz. Sound speed and attenuation were obtained using the inter-receiver broadband
      estimation technique. The measured data exhibit various frequency dependencies
      for the different mean grain sizes, consistent with earlier measurements from
      other researches. These results reveal that the trend of dispersion relation for
      the sound speed and attenuation, in the high frequency region, is strongly
      dependent on the range of Rayleigh parameter kd.

PMID- 19603851
TI  - Natural frequency of a gas bubble in a tube: experimental and simulation results.
AB  - Use of ultrasonically excited microbubbles within blood vessels has been proposed
      for a variety of clinical applications. In this paper, an axisymmetric coupled
      boundary element and finite element code and experiments have been used to
      investigate the effects of a surrounding tube on a bubble's response to acoustic
      excitation. A balloon model allowed measurement of spherical gas bubble response.
      Resonance frequencies match one-dimensional cylindrical model predictions for a
      bubble well within a rigid tube but deviate for a bubble near the tube end.
      Simulations also predict bubble translation along the tube axis and aspherical
      oscillations at higher amplitudes.

PMID- 19603852
TI  - Temporal sound field fluctuations in the presence of internal solitary waves in
      shallow water.
AB  - Temporal variations of intensity fluctuations are presented from the SWARM95
      experiment. It is hypothesized that specific features of these fluctuations can
      be explained by mode coupling due to the presence of an internal soliton moving
      approximately along the acoustic track. Estimates are presented in conjunction
      with theoretical consideration of the shallow water waveguide.

PMID- 19603853
TI  - Construction of the temporal invariants of the time-reversal operator.
AB  - This paper proposes a method to construct the temporal Green's function from a
      scatterer to an array of transducers in a waveguide using free-space back
      propagation of the eigenvectors of the time-reversal operator (TRO). The
      monostatic Green's function is obtained as an eigenvector of the TRO which is
      known with an arbitrary phase; thus the impulse response cannot be obtained by a
      simple inverse Fourier transform. Assuming that the monochromatic fields obtained
      by the back propagation of the eigenvectors are in phase at the focal point, the
      phase correction is determined. Simulations and laboratory experiments are
      presented.

PMID- 19603854
TI  - A method for time-varying annoyance rating of aircraft noise.
AB  - The method of continuous judgment by category is used and evaluated to measure
      time-varying attributes in aircraft flyover sounds. The results are also used to
      estimate preference between the different experimental sounds. Jurors were asked
      to rate perceived annoyance on a Borg CR 100 scale continuously during the
      playback of 11 flyover sequences and the results showed differences in perception
      in the time segment where the sound had been modified. The method can be used to
      evaluate maximum perceived annoyance, threshold levels, duration of perceptual
      presence temporal integration in perception, and perceptual mixtures over time.

PMID- 19603855
TI  - Amplifying effect of a release mechanism for fast adaptation in the hair bundle.
AB  - A "release" mechanism, which has been experimentally observed as the fast
      component in the hair bundle's response to mechanical stimulation, appears
      similar to common mechanical relaxation with a damping effect. This observation
      is puzzling because such a response is expected to have an amplifying role in the
      mechanoelectrical transduction process in hair cells. Here it is shown that a
      release mechanism can indeed have a role in amplification, if it is associated
      with negative stiffness due to the gating of the mechonoelectric transducer
      channel.

PMID- 19603856
TI  - An efficient code for environmental sound classification.
AB  - An efficient code for classifying environmental sounds is described that exploits
      a recent significant advance in signal processing known as compressed sensing
      (CS) [cf.Donoho, D. (2006). IEEE Trans. Inf. Theory 52, 1289-1306]. CS involves a
      novel approach to sampling in which the salient information in signals is
      recovered from the projection onto a small set of random basis functions. The
      advantage of the random basis over traditional Fourier or wavelet representations
      is that it allows accurate classification at low target-to-interference ratios
      based on few samples and little or no prior information about signals.

PMID- 19603857
TI  - Pile driving zone of responsiveness extends beyond 20 km for harbor porpoises
      (Phocoena phocoena (L.)).
AB  - Behavioral reactions of harbor porpoises (Phocoena phocoena) to underwater noise
      from pile driving were studied. Steel monopile foundations (4 m diameter) for
      offshore wind turbines were driven into hard sand in shallow water at Horns Reef,
      the North Sea. The impulsive sounds generated had high sound pressures [source
      level 235 dB re 1 microPa(pp) at 1 m, transmission loss 18 log(distance)] with a
      strong low frequency emphasis but with significant energy up to 100 kHz.
      Reactions of porpoises were studied by passive acoustic loggers (T-PODs).
      Intervals between echolocation events (encounters) were analyzed, and a
      significant increase was found from average 5.9 h between encounters in the
      construction period as a whole to on average 7.5 h between first and second
      encounters after pile driving. The size of the zone of responsiveness could not
      be inferred as no grading in response was observed with distance from the pile
      driving site but must have exceeded 21 km (distance to most distant T-POD
      station).

PMID- 19603859
TI  - Impact of meteorological conditions on noise propagation from freeway corridors.
AB  - This paper examines the impact of meteorological conditions on the propagation of
      vehicular noise from urban freeways. A parabolic equation model coupled to an
      analytical Green's function solution close to the source field is used to compute
      the refracted sound field up to half a mile from the freeway to predict the noise
      exposure of residential areas nearby. The model was used in conjunction with
      meteorological and sound-level measurements taken at two freeway sites over the
      course of four days in Phoenix, AZ. From the data collected, three test cases of
      varying levels of atmospheric stratification and wind shear are presented and
      discussed. The model demonstrates that atmospheric effects are able to raise
      sound levels by 10-20 dB at significant distances away from the highway, causing
      violations of acceptable limits imposed by the Federal Highway Administration in
      residential areas that are normally in compliance.

PMID- 19603858
TI  - Use of forward pressure level to minimize the influence of acoustic standing
      waves during probe-microphone hearing-aid verification.
AB  - Probe-microphone measurements are a reliable method of verifying hearing-aid
      sound pressure level (SPL) in the ear canal for frequencies between 0.25 and 4
      kHz. However, standing waves in the ear canal reduce the accuracy of these
      measurements above 4 kHz. Recent data suggest that speech information at
      frequencies up to 10 kHz may enhance speech perception, particularly for
      children. Incident and reflected components of a stimulus in the ear canal can be
      separated, allowing the use of forward (incident) pressure as a measure of
      stimulus level. Two experiments were conducted to determine if hearing-aid output
      in forward pressure provides valid estimates of in-situ sound level in the ear
      canal. In experiment 1, SPL measurements were obtained at the tympanic membrane
      and the medial end of an earmold in ten adults. While within-subject test-retest
      reliability was acceptable, measures near the tympanic membrane reduced the
      influence of standing waves for two of the ten participants. In experiment 2,
      forward pressure measurements were found to be unaffected by standing waves in
      the ear canal for frequencies up to 10 kHz. Implications for clinical assessment
      of amplification are discussed.

PMID- 19603860
TI  - Asynchronous control of vortex-induced acoustic cavity resonance using imbedded
      piezo-electric actuators.
AB  - This paper presents an experimental investigation of the control of a vortex
      induced acoustic cavity resonance from flow over a bluff body using embedded
      piezo-ceramic actuators in order to alter the resonant flow-acoustic
      interactions. The action of the actuators was asynchronous. Experiments were
      mainly conducted at the flow velocity of acoustic resonance, where the vortex
      shedding frequency from the upstream bluff body approached the frequency of the
      first acoustic mode of two downstream cavities. The fluctuating acoustic pressure
      was measured using a microphone. The perturbed flow field around the bluff body
      was monitored using two single hot wire anemometers and one X-wire. It was found
      that the induced transverse vibrations were effective to reduce the acoustic
      resonance. The cavity sound pressure level at resonance was reduced by 8.2 dB in
      presence of actuation. The physics behind the control mechanism is discussed.

PMID- 19603861
TI  - Green's function approximation from cross-correlation of active sources in the
      ocean.
AB  - Green's function approximation via ocean noise cross-correlation, referred to
      here as ocean acoustic interferometry, has been demonstrated experimentally for
      passive noise sources. Active sources offer the advantages of higher frequencies,
      controllability, and continuous monitoring. Experimental ocean acoustic
      interferometry is described here for two active source configurations: a source
      lowered vertically and one towed horizontally. Results are compared and
      contrasted with cross-correlations of passive noise. The results, in particular,
      differences between the empirical Green's function estimates and simulated
      Green's functions, are explained with reference to theory and simulations.
      Approximation of direct paths is shown to be consistently good for each source
      configuration. Secondary (surface reflection) paths are shown to be more accurate
      for hydrophones with a greater horizontal separation.

PMID- 19603862
TI  - Analyzing lateral seabed variability with Bayesian inference of seabed reflection
      data.
AB  - This paper considers Bayesian inversion of seabed reflection-coefficient data for
      multi-layer geoacoustic models at several sites, with the goal of studying
      lateral variability of the seabed. Rigorous uncertainty estimation is carried out
      to resolve lateral variability of the sediments from inherent inversion
      uncertainties. The uncertainty analysis includes Bayesian model selection,
      comprehensive quantification of data error statistics, and a Markov-chain Monte
      Carlo approach to transforming data uncertainties to model uncertainties. Model
      selection is addressed using the Bayesian information criterion to ensure
      parsimony of the parametrizations. Data error statistics are quantified by
      estimating full covariance matrices from data residuals, with posterior
      statistical validation. A Metropolis-Hastings sampling algorithm is used to
      compute posterior probability densities. Four experiment sites are considered
      along a track located on the Malta Plateau, Mediterranean Sea, and the inversion
      results are compared to cores taken at each site. Differences between profile
      marginal-probability distributions at adjacent sites are quantified using the
      Bhattacharyya coefficient. Differences that exceed the estimated geoacoustic
      uncertainties are interpreted as spatial variability of the seabed. The results
      are compared to an interpretation of geologic features evident in a chirp sub
      bottom-profiler section.

PMID- 19603863
TI  - Temporal and spatial coherence of sound at 250 Hz and 1659 km in the Pacific
      Ocean: demonstrating internal waves and deterministic effects explain
      observations.
AB  - The hypothesis tested is that internal gravity waves explain temporal and spatial
      coherences of sound at 1659 km in the Pacific Ocean for a signal at 250 Hz and a
      pulse resolution of 0.02 s. From data collected with a towed array, the measured
      probability that coherence time is 1.8 min or longer is 0.8. Using a parabolic
      approximation for the acoustic wave equation with sound speeds fluctuating from
      internal waves, a Monte-Carlo model yields coherence time of 1.8 min or more with
      probability of 0.9. For spatial coherence, two subsections of the array are
      compared that are separated by 142 and 370 m in directions perpendicular and
      parallel to the geodesic, respectively. Measured coherence is 0.54. This is
      statistically consistent with the modeled 95% confidence interval of [0.52,
      0.76]. The difference of 370 m parallel to the section causes spatial coherence
      to degrade deterministically by a larger amount than the effect of internal waves
      acting on the 142 m separation perpendicular to the section. The models are run
      without any tuning with data.

PMID- 19603864
TI  - Underwater acoustic beam dynamics.
AB  - Ray- and mode-based theoretical predictions of the spreads of directionally
      narrow beams are presented and compared to parabolic-equation-based simulations
      in deep-ocean environments. Both the spatial and temporal spreads of beams are
      considered. The environments considered consist of a range-independent deep-ocean
      background sound channel on which a highly structured sound-speed perturbation,
      associated with either internal waves or homogeneous isotropic single-scale
      turbulence, is superimposed. The simulation results are shown to be in good
      agreement with simple theoretical expressions which predict that beam spreading,
      in both the unperturbed and perturbed environments, is largely controlled by a
      property of the background sound channel-the ray-based stability parameter alpha
      or the asymptotically equivalent mode-based waveguide invariant beta. These
      results are consistent with earlier results showing that wavefield structure and
      stability are largely controlled by alpha (or beta).

PMID- 19603865
TI  - Determination of power-law attenuation coefficient and dispersion spectra in
      multi-wall carbon nanotube composites using Kramers-Kronig relations.
AB  - Using a broadband through-transmission technique, the attenuation coefficient and
      phase velocity spectra have been measured for a set of multi-wall carbon nanotube
      (MWCNT)-nylon composites (from pure nylon to 20% MWCNT by weight) in the
      ultrasonic frequency band from 4 to 14 MHz. The samples were found to be
      effectively homogeneous on spatial scales from the low end of ultrasonic
      wavelengths investigated and up (>0.2 mm). Using Kramers-Kronig relations, the
      attenuation and dispersion data were found to be consistent with a power-law
      attenuation model with a range of exponents from y=1.12 to y=1.19 over the
      measurement bandwidth. The attenuation coefficients of the respective samples are
      found to decrease with increasing MWCNT content and a similar trend holds also
      for the dispersion. In contrast, the mean phase velocities for the samples rise
      with increasing MWCNT content indicating an increase in the mechanical moduli.

PMID- 19603866
TI  - Sensitivity of acoustic microscopy for detecting three-dimensional nanometer gaps
      embedded in a silicon structure.
AB  - The sensitivity of acoustic microscopy for detecting three-dimensional defects in
      a Si structure is reported. Circular, nanometer gaps with diameters ranging from
      5 to 1000 microm were embedded in Si disks by a direct bonding technique, and
      these were visualized using acoustic microscopy. The limits of detection for the
      gap thickness and diameter were observed simultaneously in samples with gaps of 4
      and 140 nm. The behavior of the sensitivity in detecting the gaps can be
      explained by a simple analytical model. It is shown experimentally and
      theoretically that the gap thickness and diameter are not independent variables
      as regards detection. The sensitivity of acoustic microscopy is governed by the
      three-dimensional features of the embedded defects.

PMID- 19603867
TI  - Lamb wave characterization of corrosion-thinning in aircraft stringers:
      experiment and three-dimensional simulation.
AB  - The development of automatic guided wave interpretation for detecting corrosion
      in aluminum aircraft structural stringers is described. The dynamic wavelet
      fingerprint technique (DWFT) is used to render the guided wave mode information
      in two-dimensional binary images. Automatic algorithms then extract DWFT features
      that correspond to the distorted arrival times of the guided wave modes of
      interest, which give insight into changes of the structure in the propagation
      path. To better understand how the guided wave modes propagate through real
      structures, parallel-processing elastic wave simulations using the finite
      integration technique (EFIT) has been performed. Three-dimensional (3D)
      simulations are used to examine models too complex for analytical solutions. They
      produce informative visualizations of the guided wave modes in the structures and
      mimic the output from sensors placed in the simulation space. Using the
      previously developed mode extraction algorithms, the 3D EFIT results are compared
      directly to their experimental counterparts.

PMID- 19603868
TI  - A study of coupled flexural-longitudinal wave motion in a periodic dual-beam
      structure with transverse connection.
AB  - A theoretical study of the multi-coupling flexural and longitudinal waves that
      propagate in a periodic dual-beam-type waveguide with structural connection
      branches is conducted. The analytical equations of the transfer matrix method are
      derived for the wave transmission with consideration given to the fully flexural
      and longitudinal motions that are tri-coupled at each connection. Based on this
      transfer matrix method, numerical calculation is performed to investigate the
      characteristic wave-types that propagate in a semi-infinite periodic structure.
      The complex wave-coupling phenomena in the periodically connected dual-beam
      waveguide are then analyzed numerically. Remarkably, it is found that three
      symmetric and three antisymmetric types of characteristic coupled waves propagate
      in a periodic structure. The numerical results show that the energy contribution
      of the coupled waves with respect to the source excitation depends on the
      forbidden band of the wave-types and on the energy ratios and combination of wave
      types. This study promotes the fundamental understanding and prediction of
      coupled acoustic waves in multi-layered frame structures. The long-term
      significance is that it may lead to a more effective control method for structure
      borne sound transmission in a multi-layered coupling structure.

PMID- 19603869
TI  - Energy equipartition and frequency distribution in complex attachments.
AB  - As reported in several recent publications, an undamped simple oscillator with a
      complex attachment that consists of a set of undamped parallel resonators can
      exhibit unusual energy sharing properties. The conservative set of oscillators of
      the attachment can absorb nearly all the impulsive energy applied to the primary
      oscillator to which it is connected. The key factor in the ability of the
      attachment to absorb energy with near irreversibility correlates with the natural
      frequency distribution of the resonators within it. The reported results also
      show that a family of optimal frequency distributions can be determined on the
      basis of a variational approach, minimizing a certain functional related to the
      system response. The present paper establishes a link between these optimal
      frequency distributions and the energy equipartition principle: optimal frequency
      distributions are those that spread the injected energy as uniformly as possible
      over the degrees of freedom or over the modes of the system. Theoretical as well
      as numerical results presented support this point of view.

PMID- 19603870
TI  - Shaping of a system's frequency response using an array of subordinate
      oscillators.
AB  - The frequency response of an oscillating structure can be tailored by attaching
      one or more subordinate oscillators. This paper shows how the magnitude and phase
      of the frequency response can be deliberately shaped by prescribing the
      distributions of the dynamic properties in an array of such subordinate
      oscillators. Exact analytic governing equations of motion are derived for the
      coupled system composed of the primary system and the subordinate array. For a
      relatively small number (<100) of attached oscillators whose total mass is small
      (<1%) relative to the primary structure, it is possible to engineer frequency
      response functions of the primary oscillator to have, for example, nearly linear
      phase or constant amplitude over a frequency band of interest. The frequency
      range over which response shaping is achieved is determined by the band of the
      attached oscillators. It is shown that the common analytic methodology for
      designing a dynamic vibration absorber represents the limiting case of a single
      oscillator in the subordinate set. Moreover, increasing the number of subordinate
      oscillators (without increasing the total added mass) offers a number of
      advantages in reshaping the dominant system's frequency response.

PMID- 19603871
TI  - A numerical study of defect detection in a plaster dome ceiling using structural
      acoustics.
AB  - A numerical study is carried out to evaluate the effectiveness of using measured
      surface displacements resulting from acoustic speaker excitation to detect and
      localize flaws in a domed, plaster ceiling. The response of the structure to an
      incident acoustic pressure is obtained at four frequencies between 100 and 400 Hz
      using a parallel h-p structural acoustic finite element-based code. Three ceiling
      conditions are modeled: the pristine ceiling considered rigidly attached to the
      domed-shape support, partial detachment of a segment of the plaster layer from
      the support, and an interior pocket of plaster deconsolidation modeled as a heavy
      fluid. Spatial maps of the normal displacement resulting from speaker excitation
      are interpreted with the help of predictions based on static analysis. It is
      found that acoustic speaker excitation can provide displacement levels readily
      detected by commercially available laser Doppler vibrometer systems. Further, it
      is concluded that for 1 in. thick plaster layers, detachment sizes as small as 4
      cm are detectable by direct observation of the measured displacement maps.
      Finally, spatial structure differences are observed in the displacement maps
      beneath the two defect types, which may provide a wavenumber-based feature useful
      for distinguishing plaster detachment from other defects such as deconsolidation.

PMID- 19603872
TI  - A Burton-Miller inverse boundary element method for near-field acoustic
      holography.
AB  - An inverse boundary element method based on the Burton-Miller integral equation
      is proposed for reconstructing the Neumann boundary data from pressure values on
      a conformal surface in the near-field of an arbitrary radiating object. The
      accuracy of the reconstruction is compared with that of a method based on the
      more commonly used Helmholtz integral equation. In particular, the behavior at
      characteristic frequencies, which are known to be problematic in the Helmholtz
      integral equation for the forward problem, is examined. The effect of
      regularization is considered, including the L-curve parameter selection method.
      Numerical computations are given for noisy data generated from an internal point
      source.

PMID- 19603874
TI  - Use of the standard rubber ball as an impact source with heavyweight concrete
      floors.
AB  - To select an appropriate standard floor impact source to simulate real floor
      impacts, objective and subjective evaluations of the floor impact sounds were
      conducted in a box-frame-type structure with reinforced concrete slab floors. The
      sounds simulated in the test were those that would result from an adult walking
      barefoot, children running and jumping (represented by a heavy-weight impact
      source, such as a bang machine or an impact ball), as well as those of a person
      walking in high-heels or a lightweight object being dropped (represented by a
      tapping machine). Similarity tests between human-made impact sounds and standard
      heavy-weight impact sounds were performed. Sound quality (SQ) metrics were used
      to predict the results of the similarity tests. These results showed that the
      impact sound of an impact ball is more similar to a human-made impact sound than
      the sound of a bang machine. A multiple regression analysis showed that loudness
      and roughness are significant factors describing the results of similarity
      judgment among SQ metrics. Much of the data from the standard impact sources,
      measured in reinforced concrete floors with rigid floor coverings, have been
      collected. An empirical relationship was established to convert the impact
      pressure sound level from the bang machine or tapping machine to that from the
      impact ball. This study indicates that the use of an impact ball is reliable for
      simulating human impact sounds.

PMID- 19603873
TI  - Reconstruction of sound source pressures in an enclosure using the phased beam
      tracing method.
AB  - Source identification in an enclosure is not an easy task due to complicated wave
      interference and wall reflections, in particular, at mid-high frequencies. In
      this study, a phased beam tracing method was applied to the reconstruction of
      source pressures inside an enclosure at medium frequencies. First, surfaces of an
      extended source are divided into reasonably small segments. From each source
      segment, one beam is projected into the field and all emitted beams are traced.
      Radiated beams from the source reach array sensors after traveling various paths
      including the wall reflections. Collecting all the pressure histories at the
      field points, source-observer relations can be constructed in a matrix-vector
      form for each frequency. By multiplying the measured field data with the pseudo
      inverse of the calculated transfer function, one obtains the distribution of
      source pressure. An omni-directional sphere and a cubic source in a rectangular
      enclosure were taken as examples in the simulation tests. A reconstruction error
      was investigated by Monte Carlo simulation in terms of field point locations.
      When the source information was reconstructed by the present method, it was shown
      that the sound power of the source in an enclosure could be estimated.

PMID- 19603875
TI  - Multiple acoustic diffraction around rigid parallel wide barriers.
AB  - A ray-based method is presented for evaluating multiple acoustic diffraction by
      separate rigid and parallel wide barriers, where two or more neighboring ones are
      of equal height. Based on the geometrical theory of diffraction and extended from
      the exact boundary solution for a rigid wedge, the proposed method is able to
      determine the multiple diffraction along arbitrary directions or at arbitrary
      receiver locations around the diffracting edges, including the positions along
      the shadow or reflection boundaries or very close to the edges. Comparisons
      between the results of the numerical simulations and the boundary element method
      show validity of the proposed method.

PMID- 19603876
TI  - Annoyance from environmental noise across the lifespan.
AB  - Curvilinear effects of age on self-reported annoyance from environmental noise
      were investigated in a pooled international and a Dutch sample of in total 62,983
      individuals aged between 15 and 102 years. All respondents were frequently
      exposed to varying levels of transportation noise (i.e., aircraft, road traffic,
      and railway noise). Results reveal an inverted U-shaped pattern, where the
      largest number of highly annoyed individuals was found in the middle-aged segment
      of the sample (peaking around 45 years) while the lowest number was found in the
      youngest and oldest age segments. This pattern was independent of noise exposure
      level and self-reported noise sensitivity. The inverted U-shape explains the
      absence of linear age effects in previous studies. The results are discussed in
      light of theories predicting an age-related vulnerability to noise.

PMID- 19603877
TI  - Policy discourse, people's internal frames, and declared aircraft noise
      annoyance: an application of Q-methodology.
AB  - Aircraft noise annoyance is studied extensively, but often without an explicit
      theoretical framework. In this article, a social approach for noise annoyance is
      proposed. The idea that aircraft noise is meaningful to people within a socially
      produced discourse is assumed and tested. More particularly, it is expected that
      the noise policy discourse influences people's assessment of aircraft noise. To
      this end, Q-methodology is used, which, to the best of the authors' knowledge,
      has not been used for aircraft noise annoyance so far. Through factor analysis
      five distinct frames are revealed: "Long live aviation!," "aviation: an
      ecological threat," "aviation and the environment: a solvable problem," "aircraft
      noise: not a problem," and "aviation: a local problem." It is shown that the
      former three frames are clearly related to the policy discourse. Based on this
      observation it is argued that policy making is a possible mechanism through which
      the sound of aircraft is turned into annoyance. In addition, it is concluded that
      the experience of aircraft noise and, in particular, noise annoyance is part of
      coherent frames of mind, which consist of mutually reinforcing positions and
      include non-acoustical factors.

PMID- 19603878
TI  - Evaluating standard airborne sound insulation measures in terms of annoyance,
      loudness, and audibility ratings.
AB  - This paper reports the results of an evaluation of the merits of standard
      airborne sound insulation measures with respect to subjective ratings of the
      annoyance and loudness of transmitted sounds. Subjects listened to speech and
      music sounds modified to represent transmission through 20 different walls with
      sound transmission class (STC) ratings from 34 to 58. A number of variations in
      the standard measures were also considered. These included variations in the 8-dB
      rule for the maximum allowed deficiency in the STC measure as well as variations
      in the standard 32-dB total allowed deficiency. Several spectrum adaptation terms
      were considered in combination with weighted sound reduction index (R(w)) values
      as well as modifications to the range of included frequencies in the standard
      rating contour. A STC measure without an 8-dB rule and an R(w) rating with a new
      spectrum adaptation term were better predictors of annoyance and loudness ratings
      of speech sounds. R(w) ratings with one of two modified C(tr) spectrum adaptation
      terms were better predictors of annoyance and loudness ratings of transmitted
      music sounds. Although some measures were much better predictors of responses to
      one type of sound than were the standard STC and R(w) values, no measure was
      remarkably improved for predicting annoyance and loudness ratings of both music
      and speech sounds.

PMID- 19603879
TI  - Interference suppression for code-division multiple-access communications in an
      underwater acoustic channel.
AB  - In a code-division multiple-access communications network, the signal from a
      nearby user often creates a strong interference for the signal from a distant
      user. This is known as the near-far problem. Power control of source levels is
      ineffective in an underwater acoustic channel due to the slow sound speed.
      Interference rejection based on code orthogonality is ineffective using matched
      filter processing due to the fact that multipath arrivals effectively destroy the
      code orthogonality and that the signal arrival times between different users are
      not synchronized. An algorithm, called hyperspace cancellation by coordinate
      zeroing, is used in this paper to remove/suppress interference. Using a fast
      Walsh-Hadamard transform (FWHT) based on the interferer's code sequence, the
      interference signal is enhanced and removed by coordinate zeroing. The residual
      signal is transformed back using an inverse FWHT. The filtered data, with the
      interference signal largely removed, are processed using the desired signal code
      sequence. Two methods previously developed for direct-sequence spread-spectrum
      communications in an underwater channel are used to extract the transmitted
      symbols. Low bit error rate (<10(-2)) is found with the at-sea data for signal-to
      interference ratio as low as -8 to -11 dB.

PMID- 19603880
TI  - Modeling perceptual effects of reverberation on stereophonic sound reproduction
      in rooms.
AB  - The proposed model derives time-frequency maps to estimate perceived alterations
      due to reverberation in stereo audio signals reproduced in rooms. These
      alterations relate to monaural masking due to reverberant decay, derived via a
      computational auditory masking model and to inter-channel cues for the formation
      of the spatial position of the aural objects, derived via an inter-channel cue
      mapping module. The maps illustrate in detail the varying nature of the
      perceptually-relevant alterations due to room reverberation. Quantitative metrics
      are also introduced which were found to be proportional to reverberation
      interference, to room-reverberation time and to depend on the specific audio
      signal. A statistical approach classifies room response properties via their
      histogram distributions. Corresponding distributions were also applied to the
      proposed signal-dependent perceptual maps. Such distributions were found to be
      useful for interpreting the perceived alterations with different kinds of
      signals, such as music or speech.

PMID- 19603881
TI  - Finite element modeling of sound transmission with perforations of tympanic
      membrane.
AB  - A three-dimensional finite element (FE) model of human ear with structures of the
      external ear canal, middle ear, and cochlea has been developed recently. In this
      paper, the FE model was used to predict the effect of tympanic membrane (TM)
      perforations on sound transmission through the middle ear. Two perforations were
      made in the posterior-inferior quadrant and inferior site of the TM in the model
      with areas of 1.33 and 0.82 mm(2), respectively. These perforations were also
      created in human temporal bones with the same size and location. The vibrations
      of the TM (umbo) and stapes footplate were calculated from the model and measured
      from the temporal bones using laser Doppler vibrometers. The sound pressure in
      the middle ear cavity was derived from the model and measured from the bones. The
      results demonstrate that the TM perforations can be simulated in the FE model
      with geometrical visualization. The FE model provides reasonable predictions on
      effects of perforation size and location on middle ear transfer function. The
      middle ear structure-function relationship can be revealed with multi-field
      coupled FE analysis.

PMID- 19603882
TI  - Optimal electrode selection for multi-channel electroencephalogram based
      detection of auditory steady-state responses.
AB  - Auditory steady-state responses (ASSRs) are used for hearing threshold estimation
      at audiometric frequencies. Hearing impaired newborns, in particular, benefit
      from this technique as it allows for a more precise diagnosis than traditional
      techniques, and a hearing aid can be better fitted at an early age. However,
      measurement duration of current single-channel techniques is still too long for
      clinical widespread use. This paper evaluates the practical performance of a
      multi-channel electroencephalogram (EEG) processing strategy based on a detection
      theory approach. A minimum electrode set is determined for ASSRs with frequencies
      between 80 and 110 Hz using eight-channel EEG measurements of ten normal-hearing
      adults. This set provides a near-optimal hearing threshold estimate for all
      subjects and improves response detection significantly for EEG data with numerous
      artifacts. Multi-channel processing does not significantly improve response
      detection for EEG data with few artifacts. In this case, best response detection
      is obtained when noise-weighted averaging is applied on single-channel data. The
      same test setup (eight channels, ten normal-hearing subjects) is also used to
      determine a minimum electrode setup for 10-Hz ASSRs. This configuration allows to
      record near-optimal signal-to-noise ratios for 80% of subjects.

PMID- 19603883
TI  - Masking release for words in amplitude-modulated noise as a function of
      modulation rate and task.
AB  - For normal-hearing listeners, masked speech recognition can improve with the
      introduction of masker amplitude modulation. The present experiments tested the
      hypothesis that this masking release is due in part to an interaction between the
      temporal distribution of cues necessary to perform the task and the probability
      of those cues temporally coinciding with masker modulation minima. Stimuli were
      monosyllabic words masked by speech-shaped noise, and masker modulation was
      introduced via multiplication with a raised sinusoid of 2.5-40 Hz. Tasks included
      detection, three-alternative forced-choice identification, and open-set
      identification. Overall, there was more masking release associated with the
      closed than the open-set tasks. The best rate of modulation also differed as a
      function of task; whereas low modulation rates were associated with best
      performance for the detection and three-alternative identification tasks,
      performance improved with modulation rate in the open-set task. This task-by-rate
      interaction was also observed when amplitude-modulated speech was presented in a
      steady masker, and for low- and high-pass filtered speech presented in modulated
      noise. These results were interpreted as showing that the optimal rate of
      amplitude modulation depends on the temporal distribution of speech cues and the
      information required to perform a particular task.

PMID- 19603884
TI  - Pitch discrimination interference between binaural and monaural or diotic
      pitches.
AB  - Fundamental frequency (F0) discrimination between two sequentially presented
      complex (target) tones can be impaired in the presence of an additional complex
      tone (the interferer) even when filtered into a remote spectral region [Gockel,
      H., et al. (2004). J. Acoust. Soc. Am. 116, 1092-1104]. This "pitch
      discrimination interference" (PDI) is greatest when the interferer and target
      have similar F0s. The present study measured PDI using monaural or diotic complex
      tone interferers and "Huggins pitch" or diotic complex-tone targets. The first
      experiment showed that listeners hear a "complex Huggins pitch" (CHP),
      approximately corresponding to F0, when multiple phase transitions at harmonics
      of (but not at) F0 are present. The accuracy of pitch matches to the CHP was
      similar to that for an equally loud diotic tone complex presented in noise. The
      second experiment showed that PDI can occur when the target is a CHP while the
      interferer is a diotic or monaural complex tone. In a third experiment, similar
      amounts of PDI were observed for CHP targets and for loudness-matched diotic
      complex-tone targets. Thus, a conventional complex tone and CHP appear to be
      processed in common at the stage where PDI occurs.

PMID- 19603885
TI  - Sequential stream segregation using temporal periodicity cues in cochlear implant
      recipients.
AB  - Sequential stream segregation involves the ability of a listener to perceptually
      segregate two rapidly alternating sounds into different perceptual streams. By
      studying auditory streaming in cochlear implants (CIs), one can obtain a better
      understanding of the cues that CI recipients can use to segregate different sound
      sources, which may have relevance to such everyday activities as the
      understanding of speech in background noise. This study focuses on the ability of
      CI users to use temporal periodicity cues to perform auditory stream segregation.
      A rhythmic discrimination task involving sequences of alternating amplitude
      modulated (AM) noises is used. The results suggest that most CI users can stream
      AM noise bursts at relatively low modulation frequencies (near 80 Hz AM), but
      that this ability diminishes at higher modulation frequencies. Additionally, the
      ability of CI users to perform streaming using temporal periodicity cues appears
      to be comparable to that of normal-hearing listeners. These results imply that CI
      subjects may in certain contexts (i.e., when the talker has a low fundamental
      frequency voice) be able to use temporal periodicity cues to segregate and thus
      understand the voices of competing talkers.

PMID- 19603886
TI  - Detection of the break in interaural correlation is affected by interaural delay,
      aging, and center frequency.
AB  - This study investigated whether interaural integration is affected by introducing
      an interaural delay. In Experiment 1, both younger adults with normal hearing and
      older adults in the early stages of presbycusis were able to detect a transient
      break in interaural correlation (BIC) in the temporal middle of interaurally
      correlated wideband noises. However, their duration thresholds for detecting the
      BIC became larger with increasing interaural time difference (ITD) from 0 to 6
      ms, and the threshold increase for older participants was larger than that for
      younger participants. In Experiment 2, to investigate whether the effect of
      changing ITD on the BIC detection is frequency-dependent, 1/3-octave narrowband
      noises with various center frequencies were used as stimuli. Results show that
      the duration threshold for detecting the BIC was higher for high-frequency noises
      than for low-frequency noises. Also, with increasing ITD from 0 to 4 ms, the
      threshold increase was larger for high-frequency noises than for low-frequency
      noises. The results suggest that there are age- and frequency-related temporal
      declines in maintaining fine-structure signals for interaural integration. These
      declines may affect the recognition of sound sources in reverberant environments.

PMID- 19603887
TI  - Testing the binaural equal-loudness-ratio hypothesis with hearing-impaired
      listeners.
AB  - The primary purpose of the present experiment was to test whether the binaural
      equal-loudness-ratio hypothesis (i.e., the loudness ratio between monaural and
      binaural tones presented at the same Sound Pressure Level, SPL, is independent of
      SPL) holds for hearing-impaired listeners with bilaterally symmetrical hearing
      losses. The outcome of this experiment provided a theoretical construct for
      modeling loudness-growth functions. A cross-modality matching task between string
      length and tones was used to measure three loudness functions for eight
      listeners: two monaural (left and right) and one binaural. A multiple linear
      regression was performed to test the significance of presentation mode (monaural
      vs binaural and left vs right), level, and their interaction. Results indicate
      that monaural loudness functions differ between the ears of two listeners. The
      interaction between presentation mode (binaural/monaural) and level was
      significant for one listener. Although significant, these differences were quite
      small. Generally, the binaural equal-loudness-ratio hypothesis appears to hold
      for hearing-impaired listeners. These data also indicate that loudness-growth
      functions in two ears of an individual are more similar than loudness-growth
      functions in ears from different listeners. Finally, it is demonstrated that
      loudness-growth functions can be constructed for individual listeners from
      binaural level difference for equal-loudness data.

PMID- 19603888
TI  - Investigating the effects of stimulus duration and context on pitch perception by
      cochlear implant users.
AB  - Cochlear implant sound processing strategies that use time-varying pulse rates to
      transmit fine structure information are one proposed method for improving the
      spectral representation of a sound with the eventual goal of improving speech
      recognition in noisy conditions, speech recognition in tonal languages, and music
      identification and appreciation. However, many of the perceptual phenomena
      associated with time-varying rates are not well understood. In this study, the
      effects of stimulus duration on both the place and rate-pitch percepts were
      investigated via psychophysical experiments. Four Nucleus CI24 cochlear implant
      users participated in these experiments, which included a short-duration pitch
      ranking task and three adaptive pulse rate discrimination tasks. When duration
      was fixed from trial-to-trial and rate was varied adaptively, results suggested
      that both the place-pitch and rate-pitch percepts may be independent of duration
      for durations above 10 and 20 ms, respectively. When duration was varied and
      pulse rates were fixed, performance was highly variable within and across
      subjects. Implications for multi-rate sound processing strategies are discussed.

PMID- 19603889
TI  - Cantonese tone recognition with enhanced temporal periodicity cues.
AB  - This study investigated the contributions of temporal periodicity cues and the
      effectiveness of enhancing these cues for Cantonese tone recognition in noise. A
      multichannel noise-excited vocoder was used to simulate speech processing in
      cochlear implants. Ten normal-hearing listeners were tested. Temporal envelope
      and periodicity cues (TEPCs) below 500 Hz were extracted from four frequency
      bands: 60-500, 500-1000, 1000-2000, and 2000-4000 Hz. The test stimuli were
      obtained by combining TEPC-modulated noise signals from individual bands. For
      periodicity enhancement, temporal fluctuations in the range 20-500 Hz were
      replaced by a sinusoid with frequency equal to the fundamental frequency of
      original speech. Tone identification experiments were carried out using
      disyllabic word carriers. Results showed that TEPCs from the two high-frequency
      bands were more important for tone identification than TEPCs from the low
      frequency bands. The use of periodicity-enhanced TEPCs led to consistent
      improvement of tone identification accuracy. The improvement was more significant
      at low signal-to-noise ratios, and more noticeable for female than for male
      voices. Analysis of error distributions showed that the enhancement method
      reduced tone identification errors and did not show any negative effect on the
      recognition of segmental structures.

PMID- 19603890
TI  - Factors affecting masking release in cochlear-implant vocoded speech.
AB  - Cochlear-implant (CI) listeners generally perform better when listening to speech
      in steady-state noise than in fluctuating maskers, and the reasons for that are
      unclear. The present study presents a new hypothesis for the observed absence of
      release from masking. When listening to speech in fluctuating maskers (e.g.,
      competing talkers), CI users cannot fuse the pieces of the message over temporal
      gaps because they are not able to perceive reliably the acoustic landmarks
      introduced by obstruent consonants (e.g., stops). These landmarks are evident in
      spectral discontinuities associated with consonant closures and releases and are
      posited to aid listeners determine word/syllable boundaries. To test this
      hypothesis, normal-hearing (NH) listeners were presented with vocoded (6-22
      channels) sentences containing clean obstruent segments, but corrupted (by steady
      noise or fluctuating maskers) sonorant segments (e.g., vowels). Results indicated
      that NH listeners performed better with fluctuating maskers than with steady
      noise even when speech was vocoded into six channels. This outcome suggests that
      having access to the acoustic landmarks provided by the obstruent consonants
      enables listeners to integrate effectively pieces of the message glimpsed over
      temporal gaps into one coherent speech stream.

PMID- 19603891
TI  - Multiband product rule and consonant identification.
AB  - The multiband product rule, also known as band-independence, is a basic
      assumption of articulation index and its extension, the speech intelligibility
      index. Previously Fletcher showed its validity for a balanced mix of 20%
      consonant-vowel (CV), 20% vowel-consonant (VC), and 60% consonant-vowel-consonant
      (CVC) sounds. This study repeats Miller and Nicely's version of the hi-/lo-pass
      experiment with minor changes to study band-independence for the 16 Miller-Nicely
      consonants. The cut-off frequencies are chosen such that the basilar membrane is
      evenly divided into 12 segments from 250 to 8000 Hz with the high-pass and low
      pass filters sharing the same six cut-off frequencies in the middle. Results show
      that the multiband product rule is statistically valid for consonants on average.
      It also applies to subgroups of consonants, such as stops and fricatives, which
      are characterized by a flat distribution of speech cues along the frequency. It
      fails for individual consonants.

PMID- 19603892
TI  - Acoustic profiles of distinct emotional expressions in laughter.
AB  - Although listeners are able to decode the underlying emotions embedded in
      acoustical laughter sounds, little is known about the acoustical cues that
      differentiate between the emotions. This study investigated the acoustical
      correlates of laughter expressing four different emotions: joy, tickling,
      taunting, and schadenfreude. Analysis of 43 acoustic parameters showed that the
      four emotions could be accurately discriminated on the basis of a small parameter
      set. Vowel quality contributed only minimally to emotional differentiation
      whereas prosodic parameters were more effective. Emotions are expressed by
      similar prosodic parameters in both laughter and speech.

PMID- 19603894
TI  - Audio-visual identification of place of articulation and voicing in white and
      babble noise.
AB  - Research shows that noise and phonetic attributes influence the degree to which
      auditory and visual modalities are used in audio-visual speech perception (AVSP).
      Research has, however, mainly focused on white noise and single phonetic
      attributes, thus neglecting the more common babble noise and possible
      interactions between phonetic attributes. This study explores whether white and
      babble noise differentially influence AVSP and whether these differences depend
      on phonetic attributes. White and babble noise of 0 and -12 dB signal-to-noise
      ratio were added to congruent and incongruent audio-visual stop consonant-vowel
      stimuli. The audio (A) and video (V) of incongruent stimuli differed either in
      place of articulation (POA) or voicing. Responses from 15 young adults show that,
      compared to white noise, babble resulted in more audio responses for POA stimuli,
      and fewer for voicing stimuli. Voiced syllables received more audio responses
      than voiceless syllables. Results can be attributed to discrepancies in the
      acoustic spectra of both the noise and speech target. Voiced consonants may be
      more auditorily salient than voiceless consonants which are more spectrally
      similar to white noise. Visual cues contribute to identification of voicing, but
      only if the POA is visually salient and auditorily susceptible to the noise type.

PMID- 19603893
TI  - Cross-language differences in cue use for speech segmentation.
AB  - Two artificial-language learning experiments directly compared English, French,
      and Dutch listeners' use of suprasegmental cues for continuous-speech
      segmentation. In both experiments, listeners heard unbroken sequences of
      consonant-vowel syllables, composed of recurring three- and four-syllable
      "words." These words were demarcated by (a) no cue other than transitional
      probabilities induced by their recurrence, (b) a consistent left-edge cue, or (c)
      a consistent right-edge cue. Experiment 1 examined a vowel lengthening cue. All
      three listener groups benefited from this cue in right-edge position; none
      benefited from it in left-edge position. Experiment 2 examined a pitch-movement
      cue. English listeners used this cue in left-edge position, French listeners used
      it in right-edge position, and Dutch listeners used it in both positions. These
      findings are interpreted as evidence of both language-universal and language
      specific effects. Final lengthening is a language-universal effect expressing a
      more general (non-linguistic) mechanism. Pitch movement expresses prominence
      which has characteristically different placements across languages: typically at
      right edges in French, but at left edges in English and Dutch. Finally, stress
      realization in English versus Dutch encourages greater attention to
      suprasegmental variation by Dutch than by English listeners, allowing Dutch
      listeners to benefit from an informative pitch-movement cue even in an
      uncharacteristic position.

PMID- 19603895
TI  - Left hand finger force in violin playing: tempo, loudness, and finger
      differences.
AB  - A three-dimensional force transducer was installed in the neck of a violin under
      the A string at the D5 position in order to study the force with which the
      violinist clamps the string against the fingerboard under normal playing
      conditions. Violinists performed repetitive sequences of open A- and fingered D
      tones using the ring finger at tempi of 1, 2, 4, 8, and 16 notes/s at mezzo
      forte. At selected tempi, the effects of dynamic level and the use of different
      fingers were investigated as well. The force profiles were clearly dependent on
      tempo and dynamic level. At slow tempi, the force profiles were characterized by
      an initial pulse followed by a level force to the end of the finger contact
      period. At tempi higher than 2 Hz, only pulsed profiles were observed. The peak
      force exceeded 4.5 N at 1 and 2 Hz and decreased to 1.7 N at 16 Hz. All force and
      impulse values were lower at softer dynamic levels, and when using the ring or
      little finger compared to the index finger.

PMID- 19603896
TI  - Fundamental frequency influences the relationship between sound pressure level
      and spectral balance in female classically trained singers.
AB  - The influence of fundamental frequency (F0) on the relationship between sound
      pressure level (SPL) and spectral balance (SB) has been largely unexplored in the
      female singing voice. Five classically trained females performed a messa di voce
      across their musical F0 range. Average maximum SB rose with F0 by 0.27
      dB/semitone (ST) to B4 and then decreased, while average minimum SB fell by 0.5
      dB/ST to E5 and then generally rose. Of 318 tokens, 208 showed a linear SPL:SB
      relationship (R(2)>or=0.5), but F0 affected SPL:SB slope and intercept and their
      interaction above and below B4. The possibility that this reflects a change from
      subglottal inertance to compliance is discussed. Consistency of SB behavior
      change at B4 and E5 contrasted with variability in first-formant frequency.
      Nonlinear SPL:SB relationships did not arise from SB saturation. The presence of
      low-SPL "tails" may reflect the challenge in modifying vocal-fold adduction
      during crescendo and decrescendo. The results show that analysis of the SPL:SB
      relationship must take F0 into consideration.

PMID- 19603897
TI  - Rapid pitch correction in choir singers.
AB  - Highly and moderately skilled choral singers listened to a perfect fifth
      reference, with the instruction to complement the fifth such that a major triad
      resulted. The fifth was suddenly and unexpectedly shifted in pitch, and the
      singers' task was to shift the fundamental frequency of the sung tone
      accordingly. The F0 curves during the transitions often showed two phases, an
      initial quick and large change followed by a slower and smaller change,
      apparently intended to fine-tune voice F0 to complement the fifth. Anesthetizing
      the vocal folds of moderately skilled singers tended to delay the reaction. The
      means of the response times varied in the range 197- 259 ms depending on
      direction and size of the pitch shifts, as well as on skill and anesthetization.

PMID- 19603898
TI  - Singing in congenital amusia.
AB  - Congenital amusia is a musical disorder characterized by impaired pitch
      perception. To examine to what extent this perceptual pitch deficit may
      compromise singing, 11 amusic individuals and 11 matched controls were asked to
      sing a familiar tune with lyrics and on the syllable /la/. Acoustical analysis of
      sung renditions yielded measures of pitch accuracy (e.g., number of pitch errors)
      and time accuracy (e.g., number of time errors). The results revealed that 9 out
      of 11 amusics were poor singers, mostly on the pitch dimension. Poor singers made
      an anomalously high number of pitch interval and contour errors, produced pitch
      intervals largely deviating from the score, and lacked pitch stability; however,
      more than half of the amusics sang in-time. Amusics' variability in singing
      proficiency was related to their residual pitch perceptual ability. Thus, their
      singing deficiency might be a consequence of their perceptual deficit.
      Nevertheless, there were notable exceptions. Two amusic individuals, despite
      their impoverished perception, sang proficiently. The latter findings are
      consistent with the existence of separate neural pathways for auditory perception
      and action.

PMID- 19603899
TI  - Temperature modes for nonlinear Gaussian beams.
AB  - In assessing the influence of nonlinear acoustic propagation on thermal
      bioeffects, approximate methods for quickly estimating the temperature rise as
      operational parameters are varied can be very useful. This paper provides a
      formula for the transient temperature rise associated with nonlinear propagation
      of Gaussian beams. The pressure amplitudes for the Gaussian modes can be obtained
      rapidly using a method previously published for simulating nonlinear propagation
      of Gaussian beams. The temperature-mode series shows that the nth temperature
      mode generated by nonlinear propagation, when normalized by the fundamental, is
      weaker than the nth heat-rate mode (also normalized by the fundamental in the
      heat-rate series) by a factor of log(n)/n, where n is the mode number.
      Predictions of temperature rise and thermal dose were found to be in close
      agreement with full, finite-difference calculations of the pressure fields,
      temperature rise, and thermal dose. Applications to non-Gaussian beams were made
      by fitting the main lobe of the significant modes to Gaussian functions.

PMID- 19603900
TI  - Voice of the turtle: the underwater acoustic repertoire of the long-necked
      freshwater turtle, Chelodina oblonga.
AB  - Chelodina oblonga is a long-necked, freshwater turtle found predominantly in the
      wetlands on the Swan Coastal Plain of Western Australia. Turtles from three
      populations were recorded in artificial environments set up to simulate small
      wetlands. Recordings were undertaken from dawn to midnight. A vocal repertoire of
      17 categories was described for these animals with calls consisting of both
      complex and percussive spectral structures. Vocalizations included clacks,
      clicks, squawks, hoots, short chirps, high short chirps, medium chirps, long
      chirps, high calls, cries or wails, hooos, grunts, growls, blow bursts,
      staccatos, a wild howl, and drum rolling. Also, a sustained vocalization was
      recorded during the breeding months, consisting of pulse sequences that finished
      rhythmically. This was hypothesized to function as an acoustic advertisement
      display. Chelodina oblonga often lives in environments where visibility is
      restricted due to habitat complexity or poor light transmission due to tannin
      staining or turbidity. Thus the use of sound by turtles may be an important
      communication medium over distances beyond their visual range. This study reports
      the first records of an underwater acoustic repertoire in an aquatic chelonian.

PMID- 19603901
TI  - Analysis of the temporal structure of fish echoes using the dolphin broadband
      sonar signal.
AB  - Behavioral experiments indicate that dolphins detect and discriminate prey
      targets through echolocating broadband sonar signals. The fish echo contains
      components from multiple reflections, including those from the swim bladder and
      other organs, and can be used for the identification of fish species and the
      estimation of fish abundance. In this paper, temporal structures were extracted
      from fish echoes using the cross-correlation function and the lowpass filter.
      First, the echo was measured from an anesthetized fish in a water tank. The
      number, reflector intensity, and echo duration were shown to be dependent on the
      species, individual, and orientation of the fish. In particular, the echo
      duration provided useful information on the fish body height and for species
      identification. Second, the echo was measured from the live fish suspended by
      nylon monofilament lines in the open sea. It was shown that this duration could
      be estimated regardless of whether or not the fish were moving.

PMID- 19603902
TI  - A versatile pitch tracking algorithm: from human speech to killer whale
      vocalizations.
AB  - In this article, a pitch tracking algorithm [named discrete logarithmic Fourier
      transformation-pitch detection algorithm (DLFT-PDA)], originally designed for
      human telephone speech, was modified for killer whale vocalizations. The multiple
      frequency components of some of these vocalizations demand a spectral (rather
      than temporal) approach to pitch tracking. The DLFT-PDA algorithm derives
      reliable estimations of pitch and the temporal change of pitch from the harmonic
      structure of the vocal signal. Scores from both estimations are combined in a
      dynamic programming search to find a smooth pitch track. The algorithm is capable
      of tracking killer whale calls that contain simultaneous low and high frequency
      components and compares favorably across most signal to noise ratio ranges to the
      peak-picking and sidewinder algorithms that have been used for tracking killer
      whale vocalizations previously.

PMID- 19603903
TI  - Acoustic basis for fish prey discrimination by echolocating dolphins and
      porpoises.
AB  - The biosonar system of dolphins and porpoises has been studied for about 5
      decades and much has been learned [Au, W. W. L. (1993). The Sonar of Dolphins
      (Springer, New York)]. Most experiments have involved human-made targets; little
      is known about odontocetes' echolocation of prey. To address this issue, acoustic
      backscatter from Atlantic cod (Gadus morhua), gray mullet (Chelon labrosus),
      pollack, (Pollachius pollachius), and sea bass (Dicentrarchus labrax) was
      measured using simulated biosonar signals of the Atlantic bottlenose dolphin and
      harbor porpoise. The fish specimens were rotated so that the effects of the fish
      orientation on the echoes could be determined. Echoes had the highest amplitude
      and simplest structure when the incident angle was perpendicular to the
      longitudinal axis of the fish. The complexity of the echoes increased as the
      aspect angle of the fish moved away from the normal aspect. The echoes in both
      the time and frequency domains were easily distinguishable among the four species
      of fish and were generally consistent within species. A cochlear model consisting
      of a bank of band-passed filters was also used to analyze the echoes. The overall
      results suggest that there are sufficient acoustic cues available to discriminate
      between the four species of fish based on the echoes received, independent of
      aspect angle.

PMID- 19603904
TI  - Localization and tracking of phonating finless porpoises using towed stereo
      acoustic data-loggers.
AB  - Cetaceans produce sound signals frequently. Usually, acoustic localization of
      cetaceans was made by cable hydrophone arrays and multichannel recording systems.
      In this study, a simple and relatively inexpensive towed acoustic system
      consisting of two miniature stereo acoustic data-loggers is described for
      localization and tracking of finless porpoises in a mobile survey. Among 204
      porpoises detected acoustically, 34 individuals (approximately 17%) were
      localized, and 4 of the 34 localized individuals were tracked. The accuracy of
      the localization is considered to be fairly high, as the upper bounds of relative
      distance errors were less than 41% within 173 m. With the location information,
      source levels of finless porpoise clicks were estimated to range from 180 to 209
      dB re 1 microPa pp at 1 m with an average of 197 dB (N=34), which is over 20 dB
      higher than that estimated previously from animals in enclosed waters. For the
      four tracked porpoises, two-dimensional swimming trajectories relative to the
      moving survey boat, absolute swimming speed, and absolute heading direction are
      deduced by assuming the animal movements are straight and at constant speed in
      the segment between two consecutive locations.

PMID- 19603905
TI  - Underwater hearing sensitivity of harbor seals (Phoca vitulina) for narrow noise
      bands between 0.2 and 80 kHz.
AB  - The underwater hearing sensitivities of two 1.5-year-old female harbor seals were
      quantified in a quiet pool built specifically for acoustic research, by using a
      behavioral psychoacoustic technique. The animals were trained to respond when
      they detected an acoustic signal and not to respond when they did not ("go/no-go"
      response). Fourteen narrowband noise signals (1/3-octave bands but with some
      energy in adjacent bands), at 1/3-octave center frequencies of 0.2-80 kHz, and of
      900 ms duration, were tested. Thresholds at each frequency were measured using
      the up-down staircase method and defined as the stimulus level resulting in a 50%
      detection rate. Between 0.5 and 40 kHz, the thresholds corresponded to a 1/3
      octave band noise level of approximately 60 dB re 1 microPa (SD+/-3.0 dB). At
      lower frequencies, the thresholds increased to 66 dB re 1 microPa and at 80 kHz
      the thresholds rose to 114 dB re 1 microPa. The 1/3-octave noise band thresholds
      of the two seals did not differ from each other, or from the narrowband frequency
      modulated tone thresholds at the same frequencies obtained a few months before
      for the same animals. These hearing threshold values can be used to calculate
      detection ranges of underwater calls and anthropogenic noises by harbor seals.

PMID- 19603906
TI  - Auditory evoked potentials in a stranded Gervais' beaked whale (Mesoplodon
      europaeus).
AB  - Efforts to identify the specific causal mechanisms responsible for beaked whale
      strandings coincident with naval exercises have been hampered by lack of data
      concerning the hearing abilities of beaked whales and their physiological and
      behavioral responses to sound. In this study, auditory capabilities of a stranded
      Gervais' beaked whale (Mesoplodon europaeus) were investigated by measuring
      auditory evoked potentials. Click-evoked potentials, auditory thresholds as a
      function of frequency, and the modulation rate transfer function were determined.
      The evoked potentials and modulation rate transfer function were similar to those
      measured in other echolocating odontocetes; the upper limit of functional hearing
      was 80-90 kHz.

PMID- 19603907
TI  - Evoked response study tool: a portable, rugged system for single and multiple
      auditory evoked potential measurements.
AB  - Although the potential of using portable auditory evoked potential systems for
      field testing of stranded cetaceans has been long recognized, commercial systems
      for evoked potential measurements generally do not possess the bandwidth required
      for testing odontocete cetaceans and are not suitable for field use. As a result,
      there have been a number of efforts to develop portable evoked potential systems
      for field testing of cetaceans. This paper presents another such system, called
      the evoked response study tool (EVREST). EVREST is a Windows-based
      hardware/software system designed for calibrating sound stimuli and recording and
      analyzing transient and steady-state evoked potentials. The EVREST software
      features a graphical user interface, real-time analysis and visualization of
      recorded data, a variety of stimulus options, and a high level of automation. The
      system hardware is portable, rugged, battery-powered, and possesses a bandwidth
      that encompasses the audible range of echolocating odontocetes, making the system
      suitable for field testing of stranded or rehabilitating cetaceans.

PMID- 19603962
TI  - Virial theorem in the Kohn-Sham density-functional theory formalism: accurate
      calculation of the atomic quantum theory of atoms in molecules energies.
AB  - A new approach for computing the atom-in-molecule [quantum theory of atoms in
      molecule (QTAIM)] energies in Kohn-Sham density-functional theory is presented
      and tested by computing QTAIM energies for a set of representative molecules. In
      the new approach, the contribution for the correlation-kinetic energy (T(c)) is
      computed using the density-functional theory virial relation. Based on our
      calculations, it is shown that the conventional approach where atomic energies
      are computed using only the noninteracting part of the kinetic energy might be in
      error by hundreds of kJ/mol.

PMID- 19603963
TI  - Spin conserving natural orbital functional theory.
AB  - The natural orbital functional theory is considered for spin uncompensated
      systems, i.e., systems that have one or more unpaired electrons. The well-known
      cumulant expansion is used to reconstruct the two-particle reduced density
      matrix. A new condition to ensure the conservation of the total spin is obtained
      for the two-particle cumulant matrix. An extension of the Piris natural orbital
      functional 1 (PNOF1), based on an explicit form for the cumulant, to spin
      uncompensated systems is also considered. The theory is applied to the
      calculation of energy differences between the ground state and the lowest lying
      excited state with different spins for first-row atoms (Li, Be, B, C, N, O, and
      F) and diatomic oxygen molecule (O(2)). The values we obtained are very accurate
      results as compared to the CCSD(T) method and the experimental data.

PMID- 19603964
TI  - A combined effective fragment potential-fragment molecular orbital method. I. The
      energy expression and initial applications.
AB  - The effective fragment potential (EFP) method, a model potential for treating
      solvent effects and other intermolecular interactions, is interfaced with an
      electronic structure method, the fragment molecular orbital (FMO) method, that is
      able to retain high accuracy for ab initio calculations on large molecular
      systems. The accuracy of the total energies in this novel combined FMO/EFP method
      is assessed by comparisons with the conventional quantum mechanics (QM)/EFP
      method. The test cases are water clusters, a peptide, and a dianionic protein
      (treated with full QM and FMO) combined with water clusters (treated with EFP) at
      the RHF, B3LYP, and MP2 levels of theory. The basis sets employed range from
      minimal to augmented double zeta plus polarization. The energy differences
      between FMO/EFP and the conventional QM/EFP methods are within "chemical
      accuracy" (1 kcal/mol approximately = 4 kJ/mol).

PMID- 19603965
TI  - First- and second-order electrical properties computed at the FSMRCCSD level for
      excited states of closed-shell molecules using the constrained-variational
      approach.
AB  - Fock space multireference coupled-cluster (FSMRCC) method emerged as an efficient
      tool to describe the electronic structure of nearly degenerate cases. Development
      of linear response has been one of the challenging problems in FSMRCC due to the
      multiple-root nature of the effective Hamiltonian. A response from any of the
      roots would span the space for getting the properties. Hence, all roots perturbed
      by the external field would proliferate the excited states. We recently developed
      the FSMRCC method for the efficient evaluation of analytic response properties
      using a constrained variation approach. In this paper, we present analytic dipole
      moments and polarizabilities of H(2)O, O(3), and CH(+) molecules in low-lying
      excited states along with brief discussion of singlet triplet decoupling of (1,1)
      sector of FSMRCC resulting from spin adaptation.

PMID- 19603967
TI  - Partial photoionization cross sections of NH4 and H3O Rydberg radicals.
AB  - Photoionization cross sections for various Rydberg series that correspond to
      ionization channels of ammonium and oxonium Rydberg radicals from the outermost,
      occupied orbitals of their respective ground states are reported. These
      properties are known to be relevant in photoelectron dynamics studies. For the
      present calculations, the molecular-adapted quantum defect orbital method has
      been employed. A Cooper minimum has been found in the 3sa(1)-kpt(2) Rydberg
      channel of NH(4) beyond the ionization threshold, which provides the main
      contribution to the photoionization of this radical. However, no net minimum is
      found in the partial cross section of H(3)O despite the presence of minima in the
      3sa(1)-kpe and 3sa(1)-kpa(1) Rydberg channels. The complete oscillator strength
      distributions spanning the discrete and continuous regions of both radicals
      exhibit the expected continuity across the ionization threshold.

PMID- 19603968
TI  - Rovibrational energy levels of H3(+) with energies above the barrier to
      linearity.
AB  - The H(3)(+) potential energy surface is sampled at 5900 geometries with the
      emphasis on the nonequilibrium and asymptotic points. Apart from the Born
      Oppenheimer energy converged to the accuracy better than 0.02 cm(-1), the
      adiabatic and the leading relativistic corrections are computed at each geometry.
      To represent analytically the potential energy surface, the parameters of a power
      series are determined by fitting to the computed energy points. Possible choice
      of nuclear masses simulating the nonadiabatic effects in solving the nuclear
      Schrodinger equation is analyzed. A set of theoretically predicted rovibrational
      transitions is confronted with the experimental data in the 10,700-13,700 cm(-1)
      window of the spectra.

PMID- 19603966
TI  - The multiscale coarse-graining method. IV. Transferring coarse-grained potentials
      between temperatures.
AB  - This work develops a method for the construction of multiscale coarse-grained (MS
      CG) force fields at different temperatures based on available atomistic data at a
      given reference temperature. The validity of this theory is demonstrated
      numerically by applying it to construct MS-CG models of the Lennard-Jones liquid
      and simple point charge water model systems.

PMID- 19603969
TI  - Accurate thermochemistry for transition metal complexes from first-principles
      calculations.
AB  - The "correlation consistent Composite Approach" or ccCA is an ab initio model
      chemistry based on the single reference MP2 level of theory. By adjusting the
      basis set and level of theory of the core valence additive correction, ccCA is
      capable of reliable thermochemical predictions of inorganic and organometallic
      transition metal-containing molecules, as well as achieving chemical accuracy on
      main group species, with a mean absolute deviation of 0.89 kcal mol(-1) against
      the 147 enthalpies of formation in the G2/97 test set. For a set of 52 complexes
      containing elements Sc-Zn, ranging in size from diatomics to Ni(PF(3))(4) and
      Fe(C(5)H(2))(2), ccCA on average predicts enthalpies of formation to within +/-3
      kcal mol(-1) of the experimental result with a mean absolute deviation of 2.85
      kcal mol(-1) and a root mean square deviation of 3.77 kcal mol(-1). The ccCA
      methodology is a significant step toward quantitative theoretical modeling of
      transition metal thermodynamics.

PMID- 19603970
TI  - Isotropic periodic sum of electrostatic interactions for polar systems.
AB  - Isotropic periodic sum (IPS) is a method to calculate long-range interactions
      based on homogeneity of simulation systems. Long-range interactions are
      represented by interactions with isotropic periodic images of a defined local
      region and can be reduced to short ranged IPS potentials. The original
      electrostatic three-dimensional (3D)-IPS potential was derived based on a
      nonpolar homogeneous approximation and its application is limited to nonpolar or
      weak polar systems. This work derived a polar electrostatic 3D-IPS potential
      based on polar interactions. For the convenience of application, polynomial
      functions with rationalized coefficients are proposed for electrostatic and
      Lennard-Jones 3D-IPS potentials. Model systems of various polarities and several
      commonly used solvent systems are simulated to evaluate the 3D-IPS potentials. It
      is demonstrated that for polar systems the polar electrostatic 3D-IPS potential
      has much improved accuracy as compared to the nonpolar 3D-IPS potential. For
      homogeneous systems, the polar electrostatic 3D-IPS potential with a local region
      radius or cutoff distance of as small as 10 A can satisfactorily reproduce
      energetic, structural, and dynamic properties from the particle-meshed-Ewald
      method. For both homogeneous and heterogeneous systems, the 3D-IPS/discrete fast
      Fourier transform method using either the nonpolar or the polar electrostatic 3D
      IPS potentials results in very similar simulation results.

PMID- 19603971
TI  - Solving the eigenvalue equations of correlated vibrational structure methods:
      preconditioning and targeting strategies.
AB  - Various preconditioners and eigenvector targeting strategies in combination with
      the Davidson and Olsen methods are presented for solving eigenvalue equations
      encountered in vibrational configuration interaction, its response
      generalization, and vibrational coupled cluster response theory. The targeting
      methods allow significant flexibility and robustness in computing selected
      vibrational states, which are particularly important in the often occurring but
      nontrivial cases of near degeneracies. We have investigated the effect of a mode
      excitation level-based generally applicable preconditioning scheme aiming to
      improve the robustness of the more standard diagonal preconditioning method.
      Although increasing convergence rates may be achieved in general through a
      hierarchy of these preconditioners, the strategy is not always beneficial in
      terms of CPU time. Features of the methods are demonstrated in calculations of
      the overtone vibrational states of formaldehyde and the fundamental states of
      vinyl fluoride, vinyl chloride, vinyl bromide, and naphthalene.

PMID- 19603972
TI  - Effective-mode representation of non-Markovian dynamics: a hierarchical
      approximation of the spectral density. I. Application to single surface dynamics.
AB  - An approach to non-Markovian system-environment dynamics is described which is
      based on the construction of a hierarchy of coupled effective environmental modes
      that is terminated by coupling the final member of the hierarchy to a Markovian
      bath. For an arbitrary environment, which is linearly coupled to the subsystem,
      the discretized spectral density is replaced by a series of approximate spectral
      densities involving an increasing number of effective modes. This series of
      approximants, which are constructed analytically in this paper, guarantees the
      accurate representation of the overall system-plus-bath dynamics up to increasing
      times. The hierarchical structure is manifested in the approximate spectral
      densities in the form of the imaginary part of a continued fraction similar to
      Mori theory. The results are described for cases where the hierarchy is truncated
      at the first-, second-, and third-order level. It is demonstrated that the
      results generated from a reduced density matrix equation of motion and large
      dimensional system-plus-bath wavepacket calculations are in excellent agreement.
      For the reduced density matrix calculations, the system and hierarchy of
      effective modes are treated explicitly and the effects of the bath on the final
      member of the hierarchy are described by the Caldeira-Leggett equation and its
      generalization to zero temperature.

PMID- 19603973
TI  - Kramers-like turnover in load-dependent activated dynamics.
AB  - Recent advancement of experimental techniques at the single molecule level has
      demonstrated how an external load affects a chemical reaction which controls the
      transport of biological motor proteins. Majority of these studies are concerned
      with thermodynamically open systems. We have examined a prototype model reaction
      in terms of inertial Brownian motion of a particle in a force field subjected to
      an overdamped motion of a viscous load coupled harmonically to the particle. A
      general analytical expression for the rate constant has been derived to
      demonstrate that depending on the strength of harmonic coupling and drag
      coefficient of the load a Kramers-like turnover can be realized in the spatial
      diffusion-limited regime. The turnover reduces to a crossover between the two
      states characterized by zero-load and finite load conditions.

PMID- 19603975
TI  - Electrochemical proton-coupled electron transfer: beyond the golden rule.
AB  - Electrochemical proton-coupled electron transfer rate constant expressions that
      interpolate between the golden rule and solvent-controlled limits are derived.
      These expressions include the effects of solvent dynamics and thus are applicable
      for a wide range of vibronic couplings and solvent relaxation times. The golden
      rule limit is defined in terms of weak vibronic coupling and fast solvent
      relaxation, and the solvent-controlled limit is defined in terms of strong
      vibronic coupling and slow solvent relaxation. In the golden rule limit, the rate
      constant is proportional to the square of the vibronic coupling and is
      independent of the solvent relaxation time. In the solvent-controlled limit, the
      rate constant is independent of the vibronic coupling and increases as the
      solvent relaxation time decreases. The interconversion between the solvent
      controlled and golden rule limits can be induced by altering the proton donor
      acceptor mode frequency and the overlap between the reactant and product proton
      vibrational wave functions, as well as the electronic coupling, the solvent
      relaxation time, and the overpotential. The kinetic isotope effect behaves
      differently in the solvent-controlled and golden rule limits and thus provides a
      unique probe for characterizing electrochemical proton-coupled electron transfer
      processes. The analogous rate constant expressions for electrochemical electron
      transfer and homogeneous proton-coupled electron transfer are also presented. The
      impact of electrode overpotential, solvent relaxation time, and proton donor
      acceptor mode frequency on the rate constants are analyzed for model systems.

PMID- 19603974
TI  - Path integral evaluation of equilibrium isotope effects.
AB  - A general and rigorous methodology to compute the quantum equilibrium isotope
      effect is described. Unlike standard approaches, ours does not assume
      separability of rotational and vibrational motions and does not make the harmonic
      approximation for vibrations or rigid rotor approximation for the rotations. In
      particular, zero point energy and anharmonicity effects are described correctly
      quantum mechanically. The approach is based on the thermodynamic integration with
      respect to the mass of isotopes and on the Feynman path integral representation
      of the partition function. An efficient estimator for the derivative of free
      energy is used whose statistical error is independent of the number of imaginary
      time slices in the path integral, speeding up calculations by a factor of
      approximately 60 at 500 K and more at room temperature. We describe the
      implementation of the methodology in the molecular dynamics package AMBER 10. The
      method is tested on three [1,5] sigmatropic hydrogen shift reactions. Because of
      the computational expense, we use ab initio potentials to evaluate the
      equilibrium isotope effects within the harmonic approximation and then the path
      integral method together with semiempirical potentials to evaluate the
      anharmonicity corrections. Our calculations show that the anharmonicity effects
      amount up to 30% of the symmetry reduced reaction free energy. The numerical
      results are compared with recent experiments of Doering et al., [J. Am. Chem.
      Soc. 128, 9080 (2006); J. Am. Chem. Soc.129, 2488 (2007)] confirming the accuracy
      of the most recent measurement on 2,4,6,7,9-pentamethyl-5-(5,5-(2)H(2))methylene
      11,11a-dihydro-12H-naphthacene as well as concerns about compromised accuracy,
      due to side reactions, of another measurement on 2-methyl-10-(10,10
      (2)H(2))methylenebicyclo[4.4.0]dec-1-ene.

PMID- 19603976
TI  - Dynamics of chemically powered nanodimer motors subject to an external force.
AB  - The chemically powered self-propelled directed motions of nanodimer motors
      confined in a rectangular channel and subject to an applied external conservative
      force are investigated using hybrid molecular dynamics/multiparticle collision
      dynamics. The influence of factors, such as dimer sizes, chemical reaction type,
      and the nature of the interaction potentials between dimer monomers and solvent
      molecules, on the propulsion force and friction constant are examined. The stall
      force, for which the nanodimer has zero net velocity, and the thermodynamic
      efficiency of the motor are calculated. Both irreversible and reversible chemical
      reactions are considered. The simulation results are compared to theoretical
      predictions which are able to capture the major features of the self-propelled
      motion.

PMID- 19603977
TI  - Numerically exact quantum dynamics for indistinguishable particles: the
      multilayer multiconfiguration time-dependent Hartree theory in second
      quantization representation.
AB  - A new theory is proposed to accurately simulate quantum dynamics in systems of
      identical particles. It is based on the second quantization formalism of many
      body quantum theory, in which the Fock space is represented by occupation-number
      states. Within this representation the overall Fock space can be formally
      decomposed into smaller subspaces, and the wave function can be expressed as a
      multilayer multiconfiguration Hartree expansion involving subvectors in these
      subspaces. The theory unifies the multilayer multiconfiguration time-dependent
      Hartree theory for both distinguishable and indistinguishable particles. Specific
      formulations are given for systems of identical fermions, bosons, and
      combinations thereof. Practical implementations are discussed, especially for the
      case of fermions, to include the operator algebra that enforces the symmetry of
      identical particles. The theory is illustrated by a numerical example on
      vibrationally coupled electron transport.

PMID- 19603978
TI  - Viscoelastic properties of crystals.
AB  - We examine the question of whether fluids and crystals are differentiated on the
      basis of their zero frequency shear moduli or their limiting zero frequency shear
      viscosity. We show that while fluids, in contrast with crystals, do have a zero
      value for their shear modulus, in contradiction to a widespread presumption, a
      crystal does not have an infinite or exceedingly large value for its limiting
      zero frequency shear viscosity. In fact, while the limiting shear viscosity of a
      crystal is much larger than that of the liquid from which it is formed, its
      viscosity is much less than that of the corresponding glass that may form
      assuming the liquid is a good enough glass former.

PMID- 19603979
TI  - Quantitative prediction of gas-phase 17O nuclear magnetic shielding constants.
AB  - Benchmark calculations of (17)O NMR chemical shifts for a series of 19 molecules
      with 22 chemical shifts are presented. This includes calculations at the HF-SCF,
      DFT (BP86 and B3-LYP), MP2, CCSD(T), and for a special case full CCSDT level of
      theory using basis sets of quadruple zeta quality and better. The effects of the
      quality of the geometry, electron correlation, basis set, and the inclusion of
      zero-point vibrational and temperature corrections are discussed in detail and
      the results are compared to gas-phase experimental values. Mean and standard
      deviations are 6 and 24 ppm for HF-SCF, -20 and 14 ppm for BP86, -20 and 13 ppm
      for B3-LYP, and 26 and 12 ppm for MP2. Results at the CCSD(T)/pz3d2f level of
      theory using geometries optimized at the CCSD(T)/cc-pVTZ level of theory exhibit
      a mean deviation of 16 ppm and a standard deviation of 6 ppm. A mean deviation of
      6 ppm and a standard deviation of 4 ppm are obtained if these values are
      corrected for zero-point vibrational and temperature effects.

PMID- 19603980
TI  - Classical Wigner method with an effective quantum force: application to reaction
      rates.
AB  - We construct an effective "quantum force" to be used in the classical molecular
      dynamics part of the classical Wigner method when determining correlation
      functions. The quantum force is obtained by estimating the most important short
      time separation of the Feynman paths that enter into the expression for the
      correlation function. The evaluation of the force is then as easy as classical
      potential energy evaluations. The ideas are tested on three reaction rate
      problems. The resulting transmission coefficients are in much better agreement
      with accurate results than transmission coefficients from the ordinary classical
      Wigner method.

PMID- 19603981
TI  - One-dimensional slow invariant manifolds for spatially homogenous reactive
      systems.
AB  - A reactive system's slow dynamic behavior is approximated well by evolution on
      manifolds of dimension lower than that of the full composition space. This work
      addresses the construction of one-dimensional slow invariant manifolds for
      dynamical systems arising from modeling unsteady spatially homogeneous closed
      reactive systems. Additionally, the relation between the systems' slow dynamics,
      described by the constructed manifolds, and thermodynamics is clarified. It is
      shown that other than identifying the equilibrium state, traditional equilibrium
      thermodynamic potentials provide no guidance in constructing the systems' actual
      slow invariant manifolds. The construction technique is based on analyzing the
      composition space of the reactive system. The system's finite and infinite
      equilibria are calculated using a homotopy continuation method. The slow
      invariant manifolds are constructed by calculating attractive heteroclinic orbits
      which connect appropriate equilibria to the unique stable physical equilibrium
      point. Application of the method to several realistic reactive systems, including
      a detailed hydrogen-air kinetics model, reveals that constructing the actual slow
      invariant manifolds can be computationally efficient and algorithmically easy.

PMID- 19603982
TI  - Nuclear quantum effects in electronically adiabatic quantum time correlation
      functions: application to the absorption spectrum of a hydrated electron.
AB  - A general formalism for introducing nuclear quantum effects in the expression of
      the quantum time correlation function of an operator in a multilevel electronic
      system is presented in the adiabatic limit. The final formula includes the
      nuclear quantum time correlation functions of the operator matrix elements, of
      the energy gap, and their cross terms. These quantities can be inferred and
      evaluated from their classical analogs obtained by mixed quantum-classical
      molecular dynamics simulations. The formalism is applied to the absorption
      spectrum of a hydrated electron, expressed in terms of the time correlation
      function of the dipole operator in the ground electronic state. We find that both
      static and dynamic nuclear quantum effects distinctly influence the shape of the
      absorption spectrum, especially its high energy tail related to transitions to
      delocalized electron states. Their inclusion does improve significantly the
      agreement between theory and experiment for both the low and high frequency edges
      of the spectrum. It does not appear sufficient, however, to resolve persistent
      deviations in the slow Lorentzian-like decay part of the spectrum in the
      intermediate 2-3 eV region.

PMID- 19603983
TI  - Nonequilibrium characterization of spinodal points using short time dynamics.
AB  - Although intuitively appealing, the concept of spinodal is rigorously defined
      only in systems with infinite range interactions (mean-field systems). In short
      range systems, a pseudospinodal can be defined by extrapolation of metastable
      measurements, but the point itself is not reachable because it lies beyond the
      metastability limit. In this work we show that a sensible definition of spinodal
      points can be obtained through the short time dynamical behavior of the system
      deep inside the metastable phase by looking for a point where the system shows
      critical behavior. We show that spinodal points obtained by this method agree
      both with the thermodynamical spinodal point in mean-field systems and with the
      pseudospinodal point obtained by extrapolation of metaequilibrium behavior in
      short-range systems. With this definition, a practical determination can be
      achieved without regard for equilibration issues.

PMID- 19603984
TI  - Mechanical stability of proteins.
AB  - A number of experiments and experimentally based simulations showed that beta
      proteins are mechanically more stable than alpha-proteins. However, the theory
      that might explain this evidence is still lacking. In this paper we have
      developed a simple elastic theory, which allows to estimate critical forces for
      stretching both kinds of proteins. It has been shown that unfolding of beta
      proteins does really require notably higher forces as compared to the stretching
      of alpha-proteins.

PMID- 19603985
TI  - Coupled-cluster and density functional theory studies of the electronic
      excitation spectra of trans-1,3-butadiene and trans-2-propeniminium.
AB  - The electronic excitation spectra of trans-1,3-butadiene (CH(2)=CH-CH=CH(2)) and
      trans-2-propeniminium (CH(2)=CH-CH=NH(2)(+)) have been studied at several coupled
      cluster and time-dependent density functional theory levels using the linear
      response approach. Systematic studies employing large correlation-consistent
      basis sets show that approximate singles and doubles coupled-cluster calculations
      yield excitation energies in good agreement with experiment for all states except
      for the two lowest excited A(g) states of trans-1,3-butadiene which have
      significant multiconfigurational character. Time-dependent density functional
      theory calculations employing the generalized gradient approximation and hybrid
      functionals yield too low excitation energies in the basis set limit. In trans
      1,3-butadiene, increasing the basis set size by augmenting multiple diffuse
      functions is observed to reduce the high-lying excitation energies with most
      density functionals. The decrease in the energies is connected to the incorrect
      asymptotic behavior of the exchange-correlation potential. The results also
      demonstrate that standard density functionals are not capable of providing
      excitation energies of sufficient accuracy for experimental assignments.

PMID- 19603986
TI  - The H2O(2+) potential energy surfaces dissociating into H(+)/OH(+): theoretical
      analysis of the isotopic effect.
AB  - We present a detailed study of the potential energy surfaces of the water
      dication correlating asymptotically with O((3)P) and O((1)D). Using ab initio
      multireference configuration interaction method, we computed a large ensemble of
      data, which was used to generate a fit of each potential energy surface for
      bending angles theta > or = 80 degrees degrees and OH distances R(OH) > or = 1.0
      a.u. The fit is used to investigate the dissociation dynamics along each
      potential energy surface for several initial geometries corresponding to Franck
      Condon transition from neutral or singly ionized water molecule. For each case,
      we determine the dissociation channels and we compute the kinetic energy release
      and angular momentum distribution of the final arrangements. Among the eight
      potential energy surfaces investigated here, only the lowest triplet and the
      three lowest singlet can lead to the formation of bound residual fragment. The
      dissociation of HOD(2+) presents a strong preference for OH rather than OD bond
      breakage. It is characterized by the isotopic ratio, defined as the number of
      OD(+) over the number of OH(+) residual fragments. This ratio depends strongly on
      the shape of each potential energy surface and on the initial conditions.

PMID- 19603987
TI  - Rotationally resolved ultrahigh-resolution laser spectroscopy of the S2 (1)A1<-
      S0 (1)A1 transition of azulene.
AB  - We have observed rotationally resolved ultrahigh-resolution fluorescence
      excitation spectra of the 0(0)(0) (a-type) and 0(0)(0)+467 cm(-1) (b-type) bands
      of the S(2) (1)A(1)<--S(0) (1)A(1) transition of jet-cooled azulene. The observed
      linewidth is 0.0017 cm(-1), which corresponds to the lifetime of 3.1 ns in the
      S(2) state. Zeeman splitting of rotational lines is very small so that
      intersystem crossing to the triplet state is considered to be very slow. Inertial
      defect is very small and the molecule is considered to be planar in the S(0) and
      S(2) states (C(2v) symmetry). Rotational constants of the S(2) state are almost
      identical to those of the S(0) state, indicating that geometrical structure is
      similar in both electronic states. In this case, internal conversion (IC) by
      vibronic coupling is thought to be inactive. Therefore, the main radiationless
      transition process in the S(2) (1)A(1) state of azulene was identified to be IC
      to the S(1) (1)B(2) state. However, this S(2)-->S(1) IC is still slower than that
      of conventional polycyclic aromatic hydrocarbons. We consider it to be due to the
      shallower potential energy curve in the S(1) (1)B(2) state, which is also
      responsible for the extraordinarily fast S(1)-->S(0) IC in the isolated azulene
      molecule.

PMID- 19603988
TI  - The reaction of N2O with phenylium ions C6(H,D)5(+): an integrated experimental
      and theoretical mechanistic study.
AB  - The reaction of N(2)O (known to be an O atom donor under several conditions) with
      the phenyl cation is studied by experimental and theoretical methods. Phenyl
      cation (or phenylium), C(6)H(5)(+), and its perdeuterated derivative C(6)D(5)(+)
      are produced either by electron impact or by atmospheric pressure chemical
      ionization of adequate neutral precursors, and product mass spectra are measured
      in a guided ion beam tandem mass spectrometer. The ions C(5)(H,D)(5)(+),
      C(6)(H,D)(5)O(+), and C(3)(H,D)(3)(+) are experimentally detected as the most
      relevant reaction products. In addition, the detection of the adduct
      (C(6)H(5)N(2)O)(+), which is collisionally stabilized in the scattering cell of
      the mass spectrometer, is reported here for the first time. The reaction
      pathways, which could bring about the formation of the mentioned ions, are then
      explored extensively by density functional theory and, for the more promising
      pathways, by CASPT2/CASSCF calculations. The two reacting species (1) form
      initially a phenoxydiazonium adduct, C(6)H(5)ON(2)(+) (2a), by involving the
      empty in-plane hybrid C orbital of phenylium. The alternative attack to the ring
      pi system to produce an epoxidic adduct 2c is ruled out on the basis of the
      energetics. Then, 2a loses N(2) quite easily, thus affording the phenoxyl cation
      3. This is only the first of several C(6)H(5)O(+) isomers (4-6 and 8-12), which
      can stem from 3 upon different cleavages and formations of C-C bond and/or H
      shifts. As regards the formation of C(5)H(5)(+), among several conceivable
      pathways, a direct CO extrusion from 3 is discarded, while others appear to be
      viable to different extents, depending on the initial energy of the system. The
      easiest CO loss is from 4, with formation of the cyclopentadienyl cation 7.
      Formation of C(3)H(3)(+) is generally hindered and its detection depends again on
      the availability of some extra initial energy.

PMID- 19603989
TI  - Raman spectral signatures as conformational probes of gas phase flexible
      molecules.
AB  - A novel application of ionization-loss stimulated Raman spectroscopy (ILSRS) for
      monitoring the spectral features of four conformers of a gas phase flexible
      molecule is reported. The Raman spectral signatures of four conformers of 2
      phenylethylamine are well matched by the results of density functional theory
      calculations, showing bands uniquely identifying the structures. The measurement
      of spectral signatures by ILSRS in an extended spectral range, with a
      conventional laser source, is instrumental in facilitating the unraveling of
      intra- and intermolecular interactions that are significant in biological
      structure and activity.

PMID- 19603990
TI  - An experimental guided-ion-beam and ab initio study of the ion-molecule gas-phase
      reactions between Li+ ions and iso-C3H7Cl in their ground electronic state.
AB  - Reactive collisions between Li(+) ions and i-C(3)H(7)Cl molecules have been
      studied in the 0.20-12.00 eV center-of-mass energy range using an octopole radio
      frequency guided-ion beam apparatus recently developed in our laboratory. At low
      collision energies, dehydrohalogenation reactions giving rise to Li(C(3)H(6))(+)
      and Li(HCl)(+) are the main reaction channels, while at higher ones C(3)H(7)(+)
      and C(2)H(3)(+) become dominant, all their reactive cross sections having been
      measured as a function of the collision energy. To obtain information about the
      potential energy surfaces (PESs) on which the reactive processes take place, ab
      initio calculations at the MP2 level have been performed. For
      dehydrohalogenations, the reactive ground singlet PES shows ion-molecule adduct
      formation in both the reactant and product sides of the surface. Following the
      minimum energy path connecting both minima, an unstable intermediate and the
      corresponding barriers, both lying below the reactant's energy, have been
      characterized. The entrance channel ion-molecule adduct is also involved in the
      formation of C(3)H(7)(+), which then generates C(2)H(3)(+) via an CH(4)
      unimolecular elimination. A qualitative interpretation of the experimental
      results based on ab initio calculations is also included.

PMID- 19603991
TI  - Carbonyl sulfide isotopologues: ultraviolet absorption cross sections and
      stratospheric photolysis.
AB  - Ultraviolet absorption cross sections of the main and substituted carbonyl
      sulfide isotopologues were calculated using wavepacket dynamics. The calculated
      absorption cross section of (16)O(12)C(32)S is in very good agreement with the
      accepted experimental spectrum between 190 and 250 nm. Relative to
      (16)O(12)C(32)S, isotopic substitution shows a significant enhancement of the
      cross section for (16)O(13)C(32)S, a significant reduction for (18)O(12)C(32)S
      and (17)O(12)C(32)S and almost no change for the sulfur isotopologues
      (16)O(12)C(33)S, (16)O(12)C(34)S, and (16)O(12)C(36)S. The analysis of the
      initial wavepackets shows that these changes can be explained in terms of the
      change in the norm of the initial wavepacket. Implications for our understanding
      of the stratospheric sulfur cycle are discussed.

PMID- 19603992
TI  - A Car-Parrinello and path integral molecular dynamics study of the intramolecular
      lithium bond in the lithium 2-pyridyl-N-oxide acetate.
AB  - Lithium bonding in lithium 2-pyridyl-N-oxide acetate has been investigated using
      classic Car-Parrinello molecular dynamics (CPMD) and the path integral approach
      [path integrals molecular dynamics (PIMD)]. The simulations have been performed
      in 300 K. Structures, energies, and lithium trajectories have been determined.
      The CPMD results show that the lithium atom is generally equidistant between
      heavy atoms in the (O...Li...O) bridge. Applying quantum effects through the PIMD
      leads to similar conclusion. The theoretical lithium 2-pyridyl-N-oxide acetate
      infrared spectrum has also been determined using the CPMD calculations. This
      shows very good agreement with available experimental results and reproduces well
      the broad low-frequency band observed experimentally. In order to gain deeper
      understanding of the nature of the lithium bonding topological analysis of the
      electron localization function has been applied.

PMID- 19603993
TI  - Rovibronic analysis of the Jahn-Teller effect in CH2D2(+) at low energies.
AB  - The Jahn-Teller effect in the ground state of CH(2)D(2)(+) has been studied by
      pulsed-field-ionization zero-kinetic-energy photoelectron spectroscopy. The
      lowest three bands have been assigned to the three isomers
      CH([l])H([l])D(s)D(s)(+), CH([l])H(s)D([l])D(s)(+), and CH(s)H(s)D([l])D([l])(+),
      in which the deuterium atoms are attached to the central carbon atom by two short
      bonds, one short and one long bond, and two long bonds, respectively, and which
      have different zero-point vibrational energies. Whereas CH([l])H([l])D(s)D(s)(+)
      and CH(s)H(s)D([l])D([l])(+) can each be described by a single structure with
      C(2v) symmetry, CH([l])H(s)D([l])D(s)(+) corresponds to four equivalent C(1)
      structures that interconvert by tunneling. The rotational structure of these
      three bands is compared with predictions made on the basis of a tunneling
      Hamiltonian combined with a rotational Hamiltonian that incorporates the effects
      of the large-amplitude tunneling motion. The zero-point energies of
      CH([l])H(s)D([l])D(s)(+) and CH(s)H(s)D([l])D([l])(+) relative to that of
      CH([l])H([l])D(s)D(s)(+) are Delta = 123.6(5) cm(-1) and Delta(') = 243.2(5) cm(
      1), respectively, and the tunneling matrix element sigma coupling the four C(2v)
      equilibrium structures of CH([l])H(s)D([l])D(s)(+) is -1.7(4) cm(-1).

PMID- 19603994
TI  - Cooperative and competitive coadsorption of H2, O2, and N2 on Au(x)+ (x = 3, 5).
AB  - The reactions of the small gas-phase gold cluster cations Au(3)(+) and Au(5)(+)
      with N(2), H(2), and O(2) as well as mixtures thereof were investigated in an
      octopole ion trap under multicollision conditions. While gold cations are inert
      toward molecular oxygen, a distinct reaction time and temperature dependent
      reaction behavior was observed toward H(2) and N(2). Introducing mixtures of the
      reactive gases to the ion trap revealed both, competitive and cooperative
      coadsorption effects: (i) A competitive displacement reaction was detected for
      the coadsorption of H(2) and N(2) indicating the molecular adsorption of these
      molecules onto the gold clusters. The enthalpy of the displacement reaction
      determined from equilibrium mass spectra was found to be small (<10 kJ/mol). (ii)
      Preadsorption of N(2) enabled the cooperative coadsorption of O(2) under special
      experimental conditions (low temperature and very small amounts of N(2)). In this
      surprising cooperative reaction even Au(x)O(2y)(+) were formed via elimination of
      the initially activating nitrogen molecules, whereas such complexes were never
      detected in reactions of gold cluster cations with pure molecular oxygen.

PMID- 19603995
TI  - First-principles study of structure and quantum transport properties of C20
      fullerene.
AB  - Using first-principles density-functional theory and nonequilibrium Green's
      function formalism for quantum transport calculation, we study the electronic and
      transport properties of C(20) fullerene molecule. Our results show that the
      equilibrium conductance of C(20) molecule is near 1G(0). It is found that the I-V
      curve displays a linear region centered about V = 0 and nonlinear behavior under
      higher bias voltages and an obvious negative differential resistance phenomenon
      in a certain bias voltage range. The mechanism for the negative differential
      resistance behavior of C(20) is suggested. The present findings could be helpful
      for the application of the C(20) molecule in the field of single molecular
      devices or nanometer electronics.

PMID- 19603996
TI  - Dynamics starting at a conical intersection: application to the photochemistry of
      pyrrole.
AB  - The photochemical ring opening process in pyrrole has been investigated by
      performing classical on-the-fly dynamics using the multiconfiguration self
      consistent field method for the computation of energies and energy gradients. As
      starting point for the dynamics the conical intersection corresponding to the
      ring-puckered ring-opened structure, determined previously [Barbatti et al., J.
      Chem. Phys. 125, 164323 (2006)], has been chosen. Two sets of initial conditions
      for the nuclear velocities were constructed: (i) nuclear velocities in the
      branching (g,h) plane of the conical intersection and (ii) statistical
      distribution for all atoms. Both sets of initial conditions show very similar
      results. Reactive trajectories are only found in a very limited sector in the
      (g,h) plane and reaction products are very similar. Within the simulation time of
      1 ps, ring opening of pyrrole to the biradical NH=CH-CH(*)-CH=CH(*) chain
      followed by ring closure to a substituted cyclopropene structure (NH=CH-C(3)H(3))
      is observed. The computed structural data correlate well with the experimentally
      observed dissociation products.

PMID- 19603997
TI  - A quantum chemistry study of Diels-Alder dimerizations in benzene and anthracene.
AB  - There is considerable experimental evidence of covalent dimerization of aromatic
      compounds occurring under shock conditions. Because of their endothermicity,
      these reactions could play a large role in the shock initiation process of
      aromatic molecular explosives such as 2,4,6-trinitrotoluene and 1,3,5-triamino
      2,4,6-trinitrobenzene by withdrawing energy from the shock compression. Very
      little is known about the energetics, however, and this knowledge is crucial for
      the design of empirical force fields that can treat shock-induced chemistry. We
      have employed ab initio electronic structure and density functional methods to
      study the Diels-Alder (DA) dimerizations of benzene and anthracene. The enthalpy
      of reaction for DA benzene dimerization is predicted to be +35.9 kcal/mol. The
      stepwise pathway to this dimer involves formation of a stable triplet
      intermediate that requires 71.8 kcal/mol of energy. Transition states along both
      the concerted and stepwise pathways were optimized and the energetics of the
      reaction pathways are detailed. The former is found to be the energetically
      preferred mechanism. Nine DA dimers of anthracene were found, with six predicted
      to have dimerization DeltaH(rxn)'s of 24-55 kcal/mol, two with dimerization
      energies near zero and one that is formed through an exothermic reaction. Twelve
      triplet dimers of anthracene, with DeltaH(rxn)'s ranging from 33-50 kcal/mol, are
      also described. Finally, the potential importance of these reactions in the
      context of shock compression of these materials is discussed.

PMID- 19603998
TI  - Competing quantum effects in the dynamics of a flexible water model.
AB  - Numerous studies have identified large quantum mechanical effects in the dynamics
      of liquid water. In this paper, we suggest that these effects may have been
      overestimated due to the use of rigid water models and flexible models in which
      the intramolecular interactions were described using simple harmonic functions.
      To demonstrate this, we introduce a new simple point charge model for liquid
      water, q-TIP4P/F, in which the O-H stretches are described by Morse-type
      functions. We have parametrized this model to give the correct liquid structure,
      diffusion coefficient, and infrared absorption frequencies in quantum (path
      integral-based) simulations. The model also reproduces the experimental
      temperature variation of the liquid density and affords reasonable agreement with
      the experimental melting temperature of hexagonal ice at atmospheric pressure. By
      comparing classical and quantum simulations of the liquid, we find that quantum
      mechanical fluctuations increase the rates of translational diffusion and
      orientational relaxation in our model by a factor of around 1.15. This effect is
      much smaller than that observed in all previous simulations of empirical water
      models, which have found a quantum effect of at least 1.4 regardless of the
      quantum simulation method or the water model employed. The small quantum effect
      in our model is a result of two competing phenomena. Intermolecular zero point
      energy and tunneling effects destabilize the hydrogen-bonding network, leading to
      a less viscous liquid with a larger diffusion coefficient. However, this is
      offset by intramolecular zero point motion, which changes the average water
      monomer geometry resulting in a larger dipole moment, stronger intermolecular
      interactions, and a slower diffusion. We end by suggesting, on the basis of
      simulations of other potential energy models, that the small quantum effect we
      find in the diffusion coefficient is associated with the ability of our model to
      produce a single broad O-H stretching band in the infrared absorption spectrum.

PMID- 19603999
TI  - Physical aging in glassy o-terphenyl monitored by probe rotation.
AB  - The physical aging of o-terphenyl was studied through its influence on the
      rotation rate of probe molecules (1-naphthylazomethoxybenzene) over a temperature
      range from 231 (T(g)-12 K) to 238.5 K (T(g)-4.5 K). An optical anisotropy decay
      technique was used to monitor the molecule rotation. The rotation slows down
      strongly as the aging proceeds. It was shown that the aging dynamics is spatially
      heterogeneous. The anisotropy decay is well described under the following
      assumptions: (i) the temperature and structure dependencies of the relaxation
      time follow the Scherer-Hodge equation and (ii) the time of rotation is
      proportional to the time of structural relaxation.

PMID- 19604000
TI  - Diffusion in a nonequilibrium binary mixture of hard spheres swelling at
      different rates.
AB  - The nonequilibrium dynamics of a probe in a driven binary mixture of effective
      hard-sphere particles has been measured computationally in molecular dynamics
      simulations so as to obtain a better understanding of the energy and spatial
      correlations that persist through the coupling between the binary components. The
      driving of the particles is manifested through a change of the effective volume
      (or equivalently, diameter of the hard spheres) and each component is assumed to
      have a different time-dependent profile. Such a driving is possible in a
      suspension of one-component colloidal mesogens, for example, in which the
      particle volume has been seen to change with pH or temperature changes in the
      solution. It can also be realized by growing nanoparticles during a nucleation
      process. The full particle dynamics has been projected onto Langevin-type models
      of the probe motion by representing the environment using two different
      reservoirs and distinct bath-probe coupling coefficients with different
      nonstationary properties. The bath particles corresponding to each reservoir
      swell with time at various rates, nonsynchronously changing their volume
      fractions. Under the assumption of a weak bath-bath interactions, the coupling
      coefficients between the probe and two baths are expressed via those in the case
      of a simple-consisting of one bath-environment. The general form of the resulting
      irreversible Langevin equation is in agreement with the MD simulations of a hard
      sphere probe particle diffusing in the nonstationary binary mixture.

PMID- 19604001
TI  - Geometric interpretation of previtrification in hard sphere liquids.
AB  - We derive a microscopic criterion for the stability of hard sphere configurations
      and we show empirically that this criterion is marginally satisfied in the glass.
      This observation supports a geometric interpretation for the initial rapid rise
      in viscosity with packing fraction or previtrification. It also implies that
      barely stable soft modes characterize the glass structure, whose spatial
      extension is estimated. We show that both the short-term dynamics and activation
      processes occur mostly along those soft modes and we study some implications of
      these observations. This article synthesizes new and previous results [C. Brito
      and M. Wyart, Europhys. Lett. 76, 149 (2006); C. Brito and M. Wyart, J. Stat.
      Mech.: Theory Exp. 2007, L08003] in a unified view.

PMID- 19604002
TI  - Spin-forbidden and spin-enabled 4f(14)-->4f(13)5d(1) transitions of Yb(2+)-doped
      CsCaBr3.
AB  - The lowest part of the 4f-->5d absorption spectrum of Yb(2+)-doped CsCaBr(3)
      crystals has been calculated using methods of quantum chemistry and it is
      presented here. A first, low-intensity band is found on the low energy side of
      the spectrum, followed by several strong absorption bands, in agreement with
      experimental observations in trivalent and divalent lanthanide ions of the second
      half of the lanthanide series, doped in crystals. Based on Hund's rule, these
      transitions are usually interpreted as "spin-forbidden" and "spin-allowed"
      transitions, but this interpretation has been recently questioned in the
      literature. Here, a two-step relativistic method has been used which reveals the
      spin composition of the excited state wave functions. The forbidden band is found
      to be due to spin-forbidden transitions involving "high-spin" excited states
      because their 1 (3)T(1u) character is 90%. However, the allowed bands cannot be
      described as spin-allowed transitions involving "low-spin" excited states.
      Rather, they correspond to "spin-enabled" transitions because they get their
      intensity from limited (smaller than 45%) electric dipole enabling low-spin
      (1)T(1u) character. Calculations using a spin-free Hamiltonian revealed that the
      difference in their electronic structures is related to the fact that the
      4f(13)5d(t(2g))(1) manifold is split by an energy gap which separates the lowest
      (high-spin) 1 (3)T(1u) from the rest of terms, which, in turn, lie very close in
      energy from each other. As a consequence, the lowest spin-orbit components of 1
      (3)T(1u) are shown to remain 90% pure when spin-orbit coupling is considered,
      whereas a strong spin-orbit coupling exists between the remaining
      4f(13)5d(t(2g))(1) terms, among which the 1-3 (1)T(1u) enabling ones lie. As a
      result, there is a widespread electric dipole enabling (1)T(1u) character, which,
      although never higher than 45%, leads to a number of spin-enabled absorption
      bands.

PMID- 19604003
TI  - Quantum contributions in the ice phases: the path to a new empirical model for
      water-TIP4PQ/2005.
AB  - With a view to a better understanding of the influence of atomic quantum
      delocalization effects on the phase behavior of water, path integral simulations
      have been undertaken for almost all of the known ice phases using the TIP4P/2005
      model in conjunction with the rigid rotor propagator proposed by Muser and Berne
      [Phys. Rev. Lett. 77, 2638 (1996)]. The quantum contributions then being known, a
      new empirical model of water is developed (TIP4PQ/2005) which reproduces, to a
      good degree, a number of the physical properties of the ice phases, for example,
      densities, structure, and relative stabilities.

PMID- 19604004
TI  - Ethene stabilization on Cu(111) by surface roughness.
AB  - The molecular vibrations of ethene adsorbed on roughened Cu(111) surfaces have
      been investigated with high resolution electron energy loss spectroscopy and
      density-functional-theory calculations. The roughness was introduced by
      sputtering or evaporation of copper, respectively, on the cooled surface. We
      found stabilization of the ethene layer compared to ethene adsorbed on pristine
      Cu(111). Furthermore, two new vibrational features observed on the rough surface
      can be assigned to frustrated translations and rotations of the ethene molecule
      on surface defects and are indicative of a different binding on the rough
      surface.

PMID- 19604005
TI  - Surface chemical modification induces nanometer scale electron confinement in
      field effect device.
AB  - Design, preparation, and study of physicochemical properties of molecular
      assemblies are extremely challenging multidisciplinary research fields.
      Understanding the elementary principles that correlate these properties with
      molecular level of electronic behavior will enable us to control basic properties
      of molecule-based compounds as well as of classical semiconductors. In
      particular, chemical modification of field effect sensor devices where the metal
      gate is replaced with organic molecular layer, projects a crucial impact upon the
      electrical properties of the sensor. In these cases it is important to control
      the effects in order to ensure that the organic gate is optimized for sensing.
      Here we used fully depleted silicon-on-insulator (SOI) ion sensitive field effect
      transistor in order to analyze the projection of surface chemical modification on
      electronic performance. We suggest that surface activation and the application of
      3-aminopropyltrimethoxysilane on top of the gate dielectric introduces negative
      charge at the Si/SiO(2) interface or/and on top of the gate dielectric and
      consequently an accumulation layer that confines the electrons to the bottom of
      the SOI channel. The transistor gain postmodification is characteristic of volume
      inversion, and therefore suggests that, following modification, the channel
      electrons are confined to SOI thickness of <10 nm. Finally, measurements of pH
      sensitivity indicate that the pH sensitivity post-UV/O(3) treatment is maximized
      suggesting that the negative charge is introduced during the activation process,
      where the density of the negatively charged amphoteric sites maximized.

PMID- 19604006
TI  - A theoretical examination of known and hypothetical clathrate hydrate materials.
AB  - The recent synthesis of a new hydrogen binary hydrate with the sH structure has
      highlighted the potential storage capabilities of water clathrates [T. A.
      Strobel, C. A. Koh, and E. D. Sloan, J. Phys. Chem. B 112, 1885 (2008) and A. R.
      C. Duarte, A. Shariati, L. J. Rovetto, and C. J. Peters, J. Phys. Chem. B 112,
      1888 (2008)]. In this work, the absorption of hydrogen and the promoters used in
      the experimental work are considered using a simplified model for the host-guest
      interaction, which allows one to understand the stabilizing effects of multiple
      help molecules. Two further hypothetical clathrates, which are isostructural with
      known zeolite structures, are also investigated. It is shown that the energy
      gained by absorbing adamantane into these two frameworks is far greater than that
      gained upon absorption of adamantane into the sH structure. Hence, a clathrate
      with the same topology as the DDR (Sigma 1) zeolite may be synthesizable with
      adamantane and hydrogen as guest molecules as, in the conditions explored here,
      this phase appears to be more stable than the sH structure.

PMID- 19604007
TI  - A novel weighted density functional theory for adsorption, fluid-solid
      interfacial tension, and disjoining properties of simple liquid films on planar
      solid surfaces.
AB  - A novel weighted density functional theory (WDFT) for an inhomogeneous 12-6
      Lennard-Jones fluid is proposed based on the modified fundamental measure theory
      for repulsive contribution, the mean-field approximation for attractive
      contribution, and the first-order mean-spherical approximation with a weighted
      density for correlation contribution. Extensive comparisons of the theoretical
      results with molecular simulation and experimental data indicate that the new
      WDFT yields accurate density profiles, adsorption isotherms, fluid-solid
      interfacial tensions, as well as disjoining potentials and pressures of simple
      gases such as argon, nitrogen, methane, ethane, and neon confined in slitlike
      pores or near graphitic solid surfaces. The present WDFT performs better than the
      nonlocal density functional theory, which is frequently used in the study of
      adsorption on porous materials. Since the proposed theory possesses a good
      dimensional crossover and is able to correctly reduce to two-dimensional case, it
      performs very well even in very narrow pores. In addition, the present WDFT
      reproduces very well the supercritical fluid-solid interfacial tensions, whereas
      the theory of Sweatman underestimates them at high bulk densities. The present
      WDFT predicts that the increase in the fluid-wall attraction may change the sign
      of the interfacial tension and hence may make the wall from "phobic" to "philic"
      with respect to the fluid. The new WDFT is computationally as simple and
      efficient as the mean-field theory and avoids the second-order direct correlation
      function as an input. It provides a universal way to construct the excess
      Helmholtz free-energy functional for inhomogeneous fluids such as Yukawa, square
      well, and Sutherland fluids.

PMID- 19604008
TI  - Electronic structure of poly(azomethine) thin films.
AB  - Poly(1,4-phenylene-methylidynenitrilo-1,4-phenylenenitrilomethylidyne) (PPI)
      backbone approximated with poly(p-phenylene vinylene)like polymer composed of
      alternate phenylene and vinylenelike units is treated within pi electron
      approximation in terms of the chain composed of united atoms built up of virtual
      benzene and ethylene atoms. Electronic structure of the united atom is derived
      from interactions of benzene p and beta bands with V band of ethylene, taking
      into account that continuity of their pi systems results from overlap of
      vinylenelike highest occupied molecular orbital and lowest unoccupied molecular
      orbital orbitals with relevant components of benzene molecular orbitals having
      phase at parapositions. Electronic band structure has been derived within pi
      electron approximation in a way resembling tight binding approximation usually
      applied to semiconductors. The proposed model is suitable to interpret UV-visible
      spectra of PPI with additional explaining vibronic progressions. Additionally, an
      expected location of lone pair related level is proposed.

PMID- 19604009
TI  - Symmetry-based dipolar recoupling by optimal control: band-selective experiments
      for assignment of solid-state NMR spectra of proteins.
AB  - We present design of novel low-power homonuclear dipolar recoupling experiments
      for magic-angle-spinning solid-state NMR studies of proteins. The pulse sequences
      are developed by combining principles of symmetry-based dipolar recoupling and
      optimal control-based pulse sequence design. The scaffold of the pulse sequences
      is formed by known CN-type recoupling sequences, while the intrinsic sequence
      elements are designed using optimal control. This procedure allows for the
      development of high-performance pulse sequences demanding significantly weaker rf
      fields than previous symmetry-based pulse sequences while compensating for rf
      inhomogeneity and providing excitation over relevant ranges of chemical shifts
      for biological applications. The new recoupling experiments, referred to as
      optimal control CN ((OC)CN), are demonstrated numerically and experimentally by
      two-dimensional (2D) (13)C-(13)C and three-dimensional (3D) (15)N-(13)C-(13)C
      chemical shift correlation experiments on uniformly (13)C, (15)N-labeled
      ubiquitin. Exploiting the double-quantum, band-selective dipolar recoupling
      properties of the (OC)CN experiments, we demonstrate significant sensitivity
      enhancement for 2D and 3D correlation spectra showing exclusively one- or two
      bond correlations.

PMID- 19604010
TI  - Effect of glass-forming biopreservatives on head group rotational dynamics in
      freeze-dried phospholipid bilayers: a 31P NMR study.
AB  - (31)P NMR spectroscopy has been used to elucidate the role of glass-forming
      sugars in the preservation of dipalmitoylphosphatidylcholine (DPPC) lipid
      bilayers. (31)P wideline NMR spectra of freeze-dried pure DPPC, DPPC/trehalose,
      DPPC/glucose, and DPPC/hydroxyethyl starch (HES) mixtures collected in the
      temperature range of 25-80 degrees C have been simulated to obtain quantitative
      information about rotational dynamics and orientation of the lipid head groups in
      these media. In the case of pure DPPC, DPPC/glucose, and DPPC/HES, the gel-to
      liquid crystalline phase transition of DPPC bilayer is characterized by a sudden
      increase in the rate of rotational diffusion of the PO(4) head groups near 40
      degrees C. The corresponding rotational jump frequency increases from a few
      kilohertz in the gel phase to at least several megahertz in the liquid
      crystalline phase. On the other hand, in the case of DPPC/trehalose mixture the
      temperature of this onset of rapid head group dynamics is increased by
      approximately 10 degrees C. Trehalose reduces the lipid head group motions most
      effectively in the temperature range of T < or = 50 degrees C relevant for
      biopreservation. Additionally, and possibly more importantly, trehalose is found
      to strongly restrict any change in the orientation of the diffusion axis of the
      PO(4) head groups during the phase transformation. This unique ability of
      trehalose to maintain the dynamical and orientational rigidity of lipid head
      groups is likely to be responsible for its superior ability in biopreservation.

PMID- 19604013
TI  - Multi-axial mechanical stimulation of HUVECs demonstrates that combined loading
      is not equivalent to the superposition of individual wall shear stress and
      tensile hoop stress components.
AB  - Over the past 25 years, many laboratory based bioreactors have been used to study
      the cellular response to hemodynamic forces. The vast majority of these studies
      have focused on the effect of a single isolated hemodynamic force, generally
      consisting of a wall shear stress (WSS) or a tensile hoop strain (THS). However,
      investigating the cellular response to a single isolated force does not
      accurately represent the true in vivo situation, where a number of forces are
      acting simultaneously. This study used a novel bioreactor to investigate the
      cellular response of human umbilical vein endothelial cells (HUVECs) exposed to a
      combination of steady WSS and a range of cyclic THS. HUVECs exposed to a range of
      cyclic THS (0-12%), over a 12 h testing period, expressed an upregulation of both
      ICAM-1 and VCAM-1. HUVECs exposed to a steady WSS (0 dynes/cm2 and 25 dynes/cm2),
      over a 12 h testing period, also exhibited an ICAM-1 upregulation but a VCAM-1
      downregulation, where the greatest level of WSS stimulus resulted in the largest
      upregulation and downregulation of ICAM-1 and VCAM-1, respectively. A number of
      HUVEC samples were exposed to a high steady WSS (25 dynes/cm2) combined with a
      range of cyclic THS (0-4%, 0-8%, and 0-12%) for a 12 h testing period. The
      initial ICAM-1 upregulation, due to the WSS alone, was downregulated with the
      addition of a cyclic THS. It was observed that the largest THS (0-12%) had the
      greatest reducing effect on the ICAM-1 upregulation. Similarly, the initial VCAM
      1 downregulation, due to the high steady WSS alone, was further downregulated
      with the addition of a cyclic THS. A similar outcome was observed when HUVEC
      samples were exposed to a low steady WSS combined with a range of cyclic THS.
      However, the addition of a THS to the low WSS did not result in an expected ICAM
      1 downregulation. In fact, it resulted in a trend of unexpected ICAM-1
      upregulation. The unexpected cellular response to the combination of a steady WSS
      and a cyclic THS demonstrates that such a response could not be determined by
      simply superimposing the cellular responses exhibited by ECs exposed to a steady
      WSS and a cyclic THS that were applied in isolation.

PMID- 19604014
TI  - Gait initiation with electromyographically triggered electrical stimulation in
      people with partial paralysis.
AB  - Functional electrical stimulation (FES) facilitates ambulatory function after
      paralysis by activating the muscles of the lower extremities. Individuals with
      incomplete spinal cord injury (iSCI) retain partial volitional control of muscles
      below the level of injury, necessitating careful integration of FES with intact
      voluntary motor function for efficient walking. The FES-assisted stepping can be
      triggered automatically at a fixed rate (autotrigger), by a manual switch (switch
      trigger), or by an electromyogram-based gait-event-detector (EMG-trigger). It has
      been postulated that EMG may be a more natural command source than manual
      switches, and therefore will enable better coordination of stimulated and
      volitional motor functions necessary during gait. In this study, the above stated
      hypothesis was investigated in two volunteers with iSCI during the over-ground
      FES-assisted gait initiation. Four able-bodied volunteers provided the normative
      data for comparison. The EMG-triggered FES-assisted gait initiation was found to
      be more coordinated and dynamically more stable than autotriggered and switch
      triggered cases. This highlighted the potential of surface EMG as a natural
      command interface to better coordinate stimulated and volitional muscle
      activities during gait.

PMID- 19604015
TI  - Vascular cell adhesion molecule-1 expression in endothelial cells exposed to
      physiological coronary wall shear stresses.
AB  - Atherosclerosis is consistently found in bifurcations and curved segments of the
      circulatory system, indicating disturbed hemodynamics may participate in disease
      development. In vivo and in vitro studies have shown that endothelial cells (ECs)
      alter their gene expression in response to their hemodynamic environment, in a
      manner that is highly dependent on the exact nature of the applied forces. This
      research exposes cultured ECs to flow patterns present in the coronary arterial
      network, in order to determine the role of hemodynamic forces in plaque
      initiation. Vascular cell adhesion molecule-1 (VCAM-1) was examined as an
      indicator of plaque growth, as it participates in monocyte adhesion, which is one
      of the initial steps in the formation of fatty lesions. The hemodynamics of a
      healthy right and left coronary artery were determined by reconstructing 3D
      models from cineangiograms and employing computational fluid dynamic models to
      establish physiological coronary flow patterns. Wall shear stress (WSS) profiles
      selected from these studies were applied to ECs in a cone and plate bioreactor.
      The cone and plate system was specifically designed to be capable of reproducing
      the high frequency harmonics present in physiological waveforms. The shear
      stresses chosen represent those from regions prone to disease development and
      healthier arterial segments. The levels of the transcriptional and cell surface
      anchored VCAM-1 were quantified by flow cytometry and real time RT-PCR over a
      number of timepoints to obtain a complete picture of the relationship between
      this adhesion molecule and the applied shear stress. The WSS profiles from
      regions consistently displaying a higher incidence of plaques in vivo, induced
      greater levels of VCAM-1, particularly at the earlier timepoints. Conversely, the
      WSS profile from a straight section of vessel with undisturbed flow indicated no
      upregulation in VCAM-1 and a significant downregulation after 24 h, when compared
      with static controls. Low shear stress from the outer wall of a bifurcation
      induced four times the levels of VCAM-1 messenger ribonucleic acid (mRNA) after
      four hours when compared with levels of mRNA induced by WSS from a straight
      arterial section. This shear profile also induced prolonged expression of the
      surface protein of this molecule. The current study has provided insight into the
      possible influences of coronary hemodynamics on plaque localization, with VCAM-1
      only significantly induced by the WSS from disease prone regions.

PMID- 19604016
TI  - Quasi-steady-state displacement response of whole human cadaveric knees in a MRI
      scanner.
AB  - It is important to determine the three-dimensional nonuniform deformation of
      articular cartilage in its native environment. A new magnetic resonance imaging
      (MRI)-based technique (cartilage deformation by tag registration (CDTR)) has been
      developed, which can determine such deformations provided that the compressive
      load-displacement response of the knee reaches a quasi-steady state during cyclic
      loading. The objectives of this study were (1) to design and construct an
      apparatus to cyclically compress human cadaveric knees to physiological loads in
      a MRI scanner, (2) to determine the number of load cycles required to reach a
      quasi-steady-state load-displacement response for cyclic loading of human
      cadaveric knees, and (3) to collect sample MR images of undeformed and deformed
      states of tibiofemoral cartilage free of artifact while using the apparatus
      within a MRI scanner. An electropneumatic MRI-compatible apparatus was
      constructed to fit in a clinical MRI scanner, and a slope criterion was defined
      to indicate the point at which a quasi-steady-state load-displacement response,
      which would allow the use of CDTR, occurred during cyclic loading of a human
      knee. The average number of cycles required to reach a quasi-steady-state load
      displacement response according to the slope criterion defined herein for three
      cadaveric knee joints was 356+/-69. This indicates that human knee joint
      specimens can be cyclically loaded such that deformation is repeatable according
      to MRI requirements of CDTR. Sample images of tibiofemoral cartilage were
      obtained for a single knee joint. These images demonstrate the usefulness of the
      apparatus in a MRI scanner. Thus the results of this study are a crucial step
      toward developing a MRI-based method to determine the deformations of articular
      cartilage in whole human cadaveric knees.

PMID- 19604017
TI  - Poro-viscoelastic behavior of gelatin hydrogels under compression-implications
      for bioelasticity imaging.
AB  - Ultrasonic elasticity imaging enables visualization of soft tissue deformation
      for medical diagnosis. Our aim is to understand the role of flow-dependent and
      flow-independent viscoelastic mechanisms in the response of biphasic polymeric
      media, including biological tissues and hydrogels, to low-frequency forces.
      Combining the results of confined and unconfined compression experiments on
      gelatin hydrogels with finite element analysis (FEA) simulations of the
      experiments, we explore the role of polymer structure, loading, and boundary
      conditions in generating contrast for viscoelastic features. Feature estimation
      is based on comparisons between the biphasic poro-elastic and biphasic poro
      viscoelastic (BPVE) material models, where the latter adds the viscoelastic
      response of the solid polymer matrix. The approach is to develop a consistent FEA
      material model (BPVE) from confined compression-stress relaxation measurements to
      extract the strain dependent hydraulic permeability variation and cone-plate
      rheometer measurements to obtain the flow-independent viscoelastic constants for
      the solid-matrix phase. The model is then applied to simulate the unconfined
      compression experiment to explore the mechanics of hydropolymers under conditions
      of quasi-static elasticity imaging. The spatiotemporal distributions of fluid and
      solid-matrix behavior within the hydrogel are studied to propose explanations for
      strain patterns that arise during the elasticity imaging of heterogeneous media.

PMID- 19604019
TI  - On the stiffness matrix of the intervertebral joint: application to total disk
      replacement.
AB  - The traditional method of establishing the stiffness matrix associated with an
      intervertebral joint is valid only for infinitesimal rotations, whereas the
      rotations featured in spinal motion are often finite. In the present paper, a new
      formulation of this stiffness matrix is presented, which is valid for finite
      rotations. This formulation uses Euler angles to parametrize the rotation, an
      associated basis, which is known as the dual Euler basis, to describe the
      moments, and it enables a characterization of the nonconservative nature of the
      joint caused by energy loss in the poroviscoelastic disk and ligamentous support
      structure. As an application of the formulation, the stiffness matrix of a motion
      segment is experimentally determined for the case of an intact intervertebral
      disk and compared with the matrices associated with the same segment after the
      insertion of a total disk replacement system. In this manner, the matrix is used
      to quantify the changes in the intervertebral kinetics associated with total disk
      replacements. As a result, this paper presents the first such characterization of
      the kinetics of a total disk replacement.

PMID- 19604018
TI  - Planar biaxial mechanical behavior of bioartificial tissues possessing prescribed
      fiber alignment.
AB  - Though it is widely accepted that fiber alignment has a great influence on the
      mechanical anisotropy of tissues, a systematic study of the influence of fiber
      alignment on the macroscopic mechanical behavior by native tissues is precluded
      due to their predefined microstructure and heterogeneity. Such a study is
      possible using collagen-based bioartificial tissues that allow for alignment to
      be prescribed during their fabrication. To generate a systemic variation of
      strength of fiber alignment, we made cruciform tissue constructs in Teflon molds
      that had arms of different aspect ratios. We implemented our anisotropic biphasic
      theory of tissue-equivalent mechanics to simulate the compaction by finite
      element analysis. Prior to tensile testing, the construct geometry was
      standardized by cutting test samples with a 1:1 cruciform punch after releasing
      constructs from the molds. Planar biaxial testing was performed on these samples,
      after stretching them to their in-mold dimensions to recover in-mold alignment,
      to observe the macroscopic mechanical response with simultaneous fiber alignment
      imaging using a polarimetry system. We found that the strength of fiber alignment
      of the samples prior to release from the molds linearly increased with anisotropy
      of the mold. In testing after release, modulus ratio (modulus in fiber
      direction/modulus in normal direction) was greater as the initial strength of
      fiber alignment increased, that is, as the aspect ratio increased. We also found
      that the fiber alignment strength and modulus ratio increased in a hyperbolic
      fashion with stretching for a sample of given aspect ratio.

PMID- 19604020
TI  - Tension and combined tension-extension structural response and tolerance
      properties of the human male ligamentous cervical spine.
AB  - Tensile loading of the human cervical spine results from noncontact inertial
      loading of the head as well as mandibular and craniofacial impacts. Current
      vehicle safety standards include a neck injury criterion based on beam theory
      that uses a linear combination of the normalized upper cervical axial force and
      sagittal plane moment. This study examines this criterion by imposing combined
      axial tension and bending to postmortem human subject (PMHS) ligamentous cervical
      spines. Tests were conducted on 20 unembalmed PMHSs. Nondestructive whole
      cervical spine tensile tests with varying cranial end condition and
      anteroposterior loading location were used to generate response corridors for
      computational model development and validation. The cervical spines were
      sectioned into three functional spinal segments (Occiput-C2, C4-C5, and C6-C7)
      for measurement of tensile structural response and failure testing. The upper
      cervical spine (Occiput-C2) was found to be significantly less stiff, absorb less
      strain energy, and fail at higher loads than the lower cervical spine (C4-C5 and
      C6-C7). Increasing the moment arm of the applied tensile load resulted in larger
      head rotations, larger moments, and significantly higher tensile ultimate
      strengths in the upper cervical spine. The strength of the upper cervical spine
      when loaded through the head center of gravity (2417+/-215 N) was greater than
      when loaded over the occipital condyles (2032+/-250 N), which is not predicted by
      beam theory. Beam theory predicts that increased tensile loading eccentricity
      results in decreased axial failure loads. Analyses of the force-deflection
      histories suggest that ligament loading in the upper cervical spine depends on
      the amount of head rotation orientation, which may explain why the neck is
      stronger in combined tension and extension.

PMID- 19604021
TI  - A hyperelastic constitutive law for aortic valve tissue.
AB  - The objective of the present study was to perform biaxial testing and apply
      constitutive modeling to develop a strain energy function that accurately
      predicts the material behavior of the aortic valve leaflets. Ten leaflets from
      seven normal porcine aortic valves were biaxially stretched in a variety of
      protocols and the data combined to develop and fit a strain energy function to
      describe the material behavior. The results showed that the nonlinear anisotropic
      behavior of the aortic valve is well described by a strain energy function of two
      strain invariants, which uses only three coefficients to accurately predict the
      stress-strain behavior over a wide range of deformations. This structurally
      motivated constitutive law has many applications, including computational
      modeling for clinical and engineering valve treatments.

PMID- 19604022
TI  - Assessment of the ocular response analyzer as a tool for intraocular pressure
      measurement.
AB  - The ocular response analyzer (ORA) is a new indentation tonometer that subjects
      the cornea to an increasing then decreasing air pulse, and uses the corresponding
      two applanation pressures P1 and P2 to estimate the intraocular pressure (IOP).
      The present study aims to improve the accuracy of IOP estimation through
      representative numerical simulation of the ORA procedure. A parametric study has
      been carried out to consider the effect of corneal thickness, curvature, age, and
      true IOP on the P1 and P2 measurements. Based on the obtained database of input
      and output parameters, an equation has been suggested relating the P1 and P2
      measurements to the value of IOP. The equation is intended to make IOP estimates
      independent of corneal stiffness, which varies with size and age. The equation
      has been tested against a clinical data set obtained at Moorfields Eye Hospital
      involving 144 subjects, and found to produce IOP estimates that are less
      dependent on corneal size and age than published equations.

PMID- 19604024
TI  - Combination of CFD and DOE to analyze and improve the mass flow rate in urinary
      catheters.
AB  - The urinary catheter is a thin plastic tube that has been designed to empty the
      bladder artificially, effortlessly, and with minimum discomfort. The current CH14
      male catheter design was examined with a view to optimizing the mass flow rate.
      The literature imposed constraints to the analysis of the urinary catheter to
      ensure that a compromise between optimal flow, patient comfort, and everyday
      practicality from manufacture to use was achieved in the new design. As a result
      a total of six design characteristics were examined. The input variables in
      question were the length and width of eyelets 1 and 2 (four variables), the
      distance between the eyelets, and the angle of rotation between the eyelets. Due
      to the high number of possible input combinations a structured approach to the
      analysis of data was necessary. A combination of computational fluid dynamics
      (CFD) and design of experiments (DOE) has been used to evaluate the "optimal
      configuration." The use of CFD couple with DOE is a novel concept, which
      harnesses the computational power of CFD in the most efficient manner for
      prediction of the mass flow rate in the catheter.

PMID- 19604023
TI  - Carpal tunnel expansion by palmarly directed forces to the transverse carpal
      ligament.
AB  - This study investigated the expansion of the carpal tunnel resulting from the
      application of palmarly directed forces to the transverse carpal ligament (TCL)
      from inside the carpal tunnel. Ten fresh-frozen cadaveric hands were dissected to
      evacuate the carpal tunnel, and thus to expose the TCL. A custom lever device was
      built to apply forces, ranging from 10 N to 200 N, to the TCL. Without force
      application, the carpal tunnel area was 148.4+/-36.8 mm2. The force application
      caused the TCL to form arches with an increase in cross-sectional areas of 33.3+/
      5.6 mm2 at 10 N and 48.7+/-11.4 mm2 at 200 N, representing respective increases
      of 22.4% and 32.8% relative to the initial carpal tunnel area. The TCL length
      remained constant under the applied forces. It was found that the TCL arch
      formation was due to the narrowing of the arch width, which resulted from the
      migration of the bony insertion sites of the TCL. A geometrical model of the
      carpal tunnel was then developed to elucidate the relationships among the arch
      width, TCL length, arch height, and arch area. The model illustrated the
      effectiveness of carpal tunnel expansion by TCL elongation or arch width
      narrowing.

PMID- 19604025
TI  - In vivo model for evaluating the effects of mechanical stimulation on tissue
      engineered bone repair.
AB  - It has long been known that the bone adapts according to the local mechanical
      environment. To date, however, a model for studying the effects of functional
      mechanical loading on tissue-engineered bone repair in vivo has not yet been
      established. We have developed a rat femoral defect model, in which ambulatory
      loads are transduced through the implanted tissue-engineered construct to
      elucidate the role of the mechanical environment in functional restoration of a
      large bone defect. This model uses compliant fixation plates with integrated
      elastomeric segments, which allow transduction of ambulatory loads. Multiaxially
      and uniaxially compliant plates were characterized by mechanical testing and
      evaluated using in vivo pilot studies. In the first study, experimental limbs
      were implanted with multiaxial plates, which have a low stiffness in multiple
      loading modes. In the second study, experimental limbs were stabilized by a
      uniaxial plate, which allowed only axial deformation of the defect. X-ray scans
      and mechanical testing revealed that the multiaxial plates were insufficient to
      stabilize the defect and prevent fracture under ambulatory loads as a result of
      low flexural and torsional stiffness. The uniaxial plates, however, maintained
      integrity of the defect when implanted over a 12 week period. Postmortem microCT
      scans revealed a 19% increase in bone volume in the axially loaded limb compared
      with the contralateral standard control, and postmortem mechanical testing
      indicated that torsional strength and stiffness were increased 25.6- and 3.9
      fold, respectively, compared with the control. Finite element modeling revealed
      high strain gradients in the soft tissue adjacent to the newly formed bone within
      the implanted construct. This study introduces an in vivo model for studying the
      effects of physiological mechanical loading on tissue-engineered bone repair.
      Preliminary results using this new in vivo model with the uniaxially compliant
      plate showed positive effects of load-bearing on functional defect repair.

PMID- 19604026
TI  - Design and validation of a knee brace with feedback to reduce the rate of
      loading.
AB  - The repetitive nature of walking can lead to repetitive stress and associated
      complications due to the rate of loading (ROL) experienced by the body at the
      initial contact of the foot with the ground. An individual's gait kinematics at
      initial contact has been suggested to give rise to the ROL, and a repetitive,
      high ROL may lead to several disorders, including osteoarthritis. We present the
      design, development, and validation of a knee brace that provides feedback to the
      user during gait. The feedback consists of an auditory signal when the specific
      parameters of knee angle or tibial acceleration 50 ms prior to contact are
      exceeded. Nine women were recruited for the gait analysis, and the gait
      characteristics with and without the brace and feedback are analyzed. Our results
      indicate that using a knee brace with feedback can effectively change the gait
      kinematics used during walking, leading to a reduced ROL experienced at initial
      contact. Using a knee brace with feedback is a novel approach to gait retraining.
      Al-though the kinetics of how the subjects change in gait pattern is unknown, the
      reduced ROL experienced is significant and warrants further investigation.

PMID- 19604027
TI  - Description of a new digenean (Zoogonidae) genus and species from sub-Antarctic
      fish Patagonotothen tessellata.
AB  - Whitegonimus ozoufae n. gen., n. sp. (Digenea: Zoogonidae) is reported from the
      stomach of Patagonotothen tessellata in the harbor of Ushuaia in the Beagle
      Channel (Tierra del Fuego, Argentina) at a depth of 7-9 m. The female genital
      system structure indicates the new taxon belongs in the subfamily Lepidophyllinae
      (Zoogonidae). None of the genera previously described is similar to the new
      genus. The most important taxonomic features are the spined tegument, lack of
      enlarged circumoral spines, gonads arranged in tandem, long caeca, vitelline
      follicles extending from the level of the ventral sucker to the posterior end of
      anterior testis, and a Y-shaped excretory vesicle. Only 3 genera, Overstreetia,
      Anarhichotrema, and Pseudopalaeorchis, have testes arranged in tandem, but they
      differ from the new genus in possessing enlarged circumoral spines, oral sucker
      size, esophagus length, length of caeca, vitellaria restricted to hindbody, the
      form of the ovary, and an I-shaped excretory vesicle.

PMID- 19604029
TI  - Detectable effect size and bioassay power of mummichog (Fundulus heteroclitus)
      and fathead minnow (pimephales promelas) adult reproductive tests.
AB  - Although multiple reproductive tests have been developed in small-bodied fish to
      determine the effects of endocrine-disrupting substances, few direct comparisons
      have been made among the available tests. Side-by-side reproductive tests with
      mummichog (Fundulus heteroclitus) and fathead minnow (FHM; Pimephales promelas)
      were conducted with 0, 3, 10, and 30% effluent from a bleached kraft pulp mill in
      Saint John, New Brunswick, Canada. Egg production was significantly increased in
      mummichog exposed to 3% combined mill effluent, but no difference was observed in
      FHM. No differences were found in whole-body testosterone or estradiol levels in
      mummichog, and whole-body 11-ketotestosterone levels in males were increased in
      3% exposed fish compared to those in 10% effluent. Male FHM exposed to 30%
      effluent had increased whole-body testosterone levels, and female FHM in 30%
      effluent had decreased testosterone. No differences in estradiol or 11
      ketotestosterone were observed in FHM. Relatively limited response occurred in
      other endpoints. A comparison of the results of the present study to other
      published studies suggests that current reproductive bioassays are only sensitive
      for detecting magnitudes of change of greater than 50% and that differences exist
      in the sensitivities of fish. Future research should address methods of reducing
      variability within test populations and focus on understanding the comparative
      responses among species commonly used for endocrine-disrupting substance testing.

PMID- 19604030
TI  - Ebullition-facilitated transport of manufactured gas plant tar from contaminated
      sediment.
AB  - Manufactured gas plant (MGP) tar and wastewater solids historically were
      discharged into the Penobscot River, Maine,USA, via a sewer at the Bangor Landing
      site. The tar and wastewater solids accumulated in riverbed sediment over a 5
      hectare area downstream from the sewer outfall. Much of the tarry sediment is a
      hardened mass at the bottom of the river, but in part of the tar deposit (the
      active zone), the tar remains unhardened. In the active zone, anaerobic
      biodegradation of organic matter generates methane and carbon dioxide; as gas
      accumulates and migrates upward, it entrains tar, eventually dragging the tar
      from the sediment to surface water. Understanding the migration mechanisms in
      different portions of the tar deposit is critical for modeling the risk posed by
      the tar at the Bangor Landing site, because during gas-facilitated tar migration,
      the tar is brought to the water surface, instead of remaining in the sediment.
      Tar migration from sediment poses a potential human health risk because of the
      high concentrations of polycyclic aromatic hydrocarbons in the tar. Migration
      from sediment to the water surface greatly increases the potential exposure of
      human and ecological receptors to tar that reaches the water surface. In order
      for tar to migrate from sediment to surface water, three conditions are
      necessary: the sediment must contain liquid tar, the sediment must produce gas
      bubbles, and the gas must come into contact with the tarry sediment. Failure to
      consider facilitated transport of MGP tar from sediment can cause underestimation
      of site risk and can lead to failure of remedial measures.

PMID- 19604031
TI  - Agrichemicals in Nebraska, USA, watersheds: occurrence and endocrine effects.
AB  - The objective of the present study was to determine the occurrence and endocrine
      effects of agrichemicals in four Nebraska, USA, watersheds--the Elkhorn, Platte,
      Niobrara, and Dismal rivers. Land use in the Elkhorn River and Platte River
      watersheds is characterized by intense agriculture, including row crop and beef
      cattle production. In contrast, land within the Niobrara River and Dismal River
      watersheds consists primarily of grasslands. Polar organic chemical integrative
      samplers (POCIS) and caged fathead minnows were deployed at a site within each
      watershed for 7 d. The POCIS were analyzed for pesticides and hormones, while the
      caged minnows were analyzed for the expression of estrogen- and androgen
      responsive genes. Amounts of pesticides recovered in POCIS extracts from the
      Elkhorn and Platte rivers were higher than those recovered from the Niobrara and
      Dismal rivers. Furthermore, female minnows deployed in the Elkhorn River
      experienced significant reductions in expression of two estrogen-responsive genes
      (vitellogenin and estrogen receptor alpha) relative to females deployed at the
      other sites, indicating alterations in endocrine function. However, the
      defeminization of these females could not be definitely linked to any of the
      agrichemicals detected in the POCIS recovered from the Elkhorn River.

PMID- 19604032
TI  - High arctic ponds receiving biotransported nutrients from a nearby seabird colony
      are also subject to potentially toxic loadings of arsenic, cadmium, and zinc.
AB  - The role of northern fulmars (Fulmarus glacialis) was investigated for the
      transport of nutrients and trace elements to a series of 10 ponds located along a
      gradient of seabird influence below a fulmar colony in the high Arctic (Cape
      Vera, Devon Island, Canada). Phosphorus, Cd, K, Zn, and As were identified as
      seabird-derived elements, having both a high concentration in fulmar guano and a
      low concentration in background pond sediments (i.e., a high biogenic enrichment
      factor). Fluxes of these elements were highest in the pond closest to the colony
      and declined exponentially with distance. Sediments in several of the ponds
      exceeded Canadian Sediment Quality Guidelines for the Protection of Aquatic Life
      set for As (5.9 mg/kg) and Cd (0.6 mg/kg), and in the pond closest to the colony,
      which receives the most seabird subsidies, sediments contained 343 mg/kg Zn,
      exceeding the threshold for probable adverse biological effects. Although
      nutrient subsidies from fulmars create an Arctic oasis at Cape Vera, which
      supports a variety of flora and fauna, the same biological transport pathway puts
      at risk some of these species by creating sedimentary As, Cd, and Zn
      concentrations at this remote site similar to those usually observed only near
      industrialized locations.

PMID- 19604034
TI  - New species of Crossobothrium (Cestoda: Tetraphyllidea) from the broadnose
      sevengill shark, Notorynchus cepedianus, in Argentina.
AB  - Two new species of Crossobothrium were found inhabiting Notorynchus cepedianu s,
      the broadnose sevengill shark, collected from the coast of Buenos Aires Province,
      Argentina. Crossobothrium antonioi n. sp. is the smallest species in the genus
      and has at least 3 times as many testes per mature proglottid than any other
      congener. It can be further distinguished from other species of Crossobothrium by
      the possession of crenulated bothridial margins and a different microthrix
      pattern. Crossobothrium pequeae n. sp. is distinguished from all other species in
      the genus using the following combination of characters: worm size, number of
      testes per mature proglottid, bothridial margins, microthrix pattern, and the
      extension of ovary and testicular fields in cross section. Species in
      Crossobothrium, with the exception of C. laciniatum , seem to be restricted to
      hexanchid sharks, and a single species of shark can be parasitized by multiple
      species of Crossobothrium, as is the case with N. cepedianus, and probably
      Hexanchus griseus.

PMID- 19604033
TI  - Characterization of the methionine sulfoxide reductases of Schistosoma mansoni.
AB  - Schistosomiasis, also known as Bilharzia, is an infectious disease caused by
      several species of Schistosoma. Twenty million individuals suffer severe symptoms
      and 200,000 people die annually from the disease. The host responds to the
      presence of S. mansoni by producing reactive oxygen species that cause oxidative
      stress. We hypothesized that schistosomes produce antioxidants in response to
      oxidative stress. A known antioxidant protein is methionine sulfoxide reductase
      (Msr). Methionine residues can be oxidized to methionine sulfoxide in the
      presence of oxidizing agents, and the process is readily reversed by the action
      of the Msr system. Two S. mansoni MsrB genes (MsrB1 and MsrB2) were cloned and
      the recombinant proteins were expressed in bacteria and purified. The S. mansoni
      MsrB proteins contained the common conserved catalytic-and zinc-coordinating
      cysteines. Analysis of the proteins showed that both proteins promote the
      reduction of both free methionine sulfoxide (Met[O]) and dabsyl-Met(O) to free
      methionine (Met) and dabsyl-Met, respectively, while exhibiting differences in
      their specific activities toward these substrates. Using real-time polymerase
      chain reaction (RT-PCR), both proteins were found to be expressed in all stages
      of the parasite's life cycle, with the highest level of expression of both
      proteins in the egg stage. This is the first description of MsrB proteins from a
      parasite.

PMID- 19604035
TI  - Species-dependent hepatic metabolism of immunosuppressive agent tacrolimus (FK
      506).
AB  - The current study aims to investigate species-related differences in the in-vitro
      hepatic metabolism of tacroliums using liver microsomes obtained from rat,
      hamster, guinea pig, rabbit, pig, dog, baboon and humans. Tacrolimus metabolism
      was characterized using high-performance liquid chromatography- ultraviolet light
      (HPLC-UV) and two soft ionization mass spectrometric techniques; matrix-assisted
      lasers desorption/ionization (MALDI) and time-of-flight-secondary ion mass
      spectrometry (TOF-SIMS). The extent of tacrolimus metabolism, when normalized to
      the cytochrome P-450 content, was in the order: rat < hamster < rabbit < pig <
      guinea pig < dog < human < baboon. Tacrolimus metabolism exhibited significant
      qualitative and quantitative differences between the animal species tested.
      Desmethyl- (MI-MIII), didesmethyl- (MIV-MVI), monohydroxy- (MVII), dihydroxy-
      (MVIII), epoxide- (MIX), dihydrodiol- (MX), monodesmethyl and monohydroxy- (MXI
      MXIII), and didesmethyl and monohydroxy- (MXIV-MXVI) tacroliums metabolites were
      identified in the species tested. MI-MX were identified in all the species
      tested; MXI-MXVI were identified in all species except rat, rabbit and guinea
      pig; and MXIV-MXVI were identified only in baboon. The current investigation was
      unable to detect any phase II metabolites due to the limitations of the test
      system used. The analytical methods were not able to differentiate optical and
      positional isomers of metabolites due to the nature of the analytical tools used,
      therefore groups of metabolites were identified based on their molecular weights
      and available information. From the current in-vitro metabolism studies, the
      pattern of tacroliums metabolism in baboons closely resembled that in humans and
      thus it is ideal for studying tacroliums metabolism-related work of clinical
      relevance.

PMID- 19604036
TI  - Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy
      male subjects.
AB  - The aim of the study was to determine the pharmacokinetics of losartan in
      relation to the CYP2C9*13 allele. A single oral dose of 50 mg losartan was
      administrated to each of the 16 healthy male volunteers with a different genotype
      (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples
      were collected from pre-dose up to 24 h after the drug administration. Plasma
      losartan and E3174 (an active metabolite of losartan) were assayed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). All the subjects finished the
      study without adverse drug effects. In the present study, the frequencies of
      CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers,
      respectively, and both alleles were in Hardy-Weinberg equilibrium. Compared with
      the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13
      genotype showed significantly a longer t(1/2) of losartan and E3174 and markedly
      increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3
      genotype group had significant differences in t(1/2) and Cmax of E3174 compared
      with the CYP2C9*1/*1 group. The ratio of AUC(E3174)/AUC(losartan) after losartan
      administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically
      different from that in the CYP2C9*1/*1 group. The data indicate that the presence
      of the CYP2C9*13 allele results in poor metabolism of losartan after a single
      oral dose.

PMID- 19604038
TI  - Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated
      human adult chondrocytes via stimulation of endogenous TGFbeta1 production.
AB  - In vitro chondrocyte expansion is required for several cell-based approaches for
      the repair of chondral lesions. During expansion, loss of chondrogenic phenotype
      takes place (dedifferentiation). The objective of this study was to investigate
      calcineurin (Cn) as a potential target to improve chondrocyte phenotype for
      cartilage repair purposes. Cn activity in human articular chondrocytes was
      significantly increased during dedifferentiation and decreased during
      redifferentiation in vitro. Inhibition of Cn activity by FK506 increased the
      expression of chondrogenic markers collagen type 2, aggrecan, and SOX9 in culture
      expanded cells. Addition of FK506 increased endogenous transforming growth factor
      2 (TGF) beta1 expression on both mRNA and protein level. The effect of FK506 on
      chondrogenic markers was abolished by addition of anti-TGFbeta1 antibody,
      indicating that the endogenous TGFbeta1 was necessary to increase chondrogenic
      marker expression. We also showed that chondrocyte redifferentiation by TGFbeta
      requires calcium influx and does not depend on changes in Cn activity. In
      conclusion, inhibition of Cn activity by FK506 increases the expression of
      chondrogenic markers via endogenous TGFbeta1 production in human articular
      chondrocytes. Cn inhibitors might be an alternative for the application of
      (recombinant) TGFbeta, to promote chondrocyte phenotype for cell-based cartilage
      repair procedures.

PMID- 19604037
TI  - Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for
      monitoring oncogenic signaling pathways in various cancer cells.
AB  - Targeting dysregulated signaling pathways in tumors has led to the development of
      a novel class of signal transduction inhibitors, including inhibitors of the
      epidermal growth factor (EGF) receptor (EGFR). To dissect oncogenic pathways,
      identify key pathway determinants, and evaluate the efficacy of targeted agents,
      it is vital to develop technologies that allow the detection of temporal
      signaling events under physiological conditions. Here we report the application
      of a label-free optical biosensor to reveal the rapid response of cancer cells to
      EGF, expressed as a dynamic mass redistribution (DMR) signal. In response to EGF,
      squamous cell carcinoma of the head and neck cells exhibited a rapid rise in DMR
      signal, whereas lung adenocarcinoma cells showed a biphasic DMR profile,
      suggesting a cell type-dependent DMR response. Pharmacological studies suggested
      the importance of EGFR and the phosphatidylinositol-3 kinase pathway in mediating
      the EGF-induced DMR response. The defined DMR signatures offer a simple yet
      sensitive tool for evaluating EGFR-targeted agents, as shown with gefitinib and
      erlotinib. The assay can also be used for cell-based high-throughput screening of
      EGF pathway inhibitors, as demonstrated by its robust performance in a 384-well
      plate format (Z' > 0.5). This technology is applicable to other oncogenic
      pathways for the discovery of novel therapeutic agents for the treatment of
      various cancers.

PMID- 19604039
TI  - Xenogenic transplantation of human mesenchymal stem cells in a critical size
      defect of the sheep tibia for bone regeneration.
AB  - Mesenchymal stem cells (MSCs) represent an attractive cell population for the
      regeneration of mesenchymal tissues. Their special immunological characteristics
      suggest that MSCs could be used in nonautologous applications. In this study, the
      regenerative capacity of human and ovine MSCs was assessed in an ovine critical
      size defect model. Human and ovine MSCs from bone marrow were cultured on
      mineralized collagen and implanted into a 3.0-cm-long sheep tibia bone defect (n
      = 7). Unloaded mineralized collagen served as control. Bone healing was assessed
      until euthanasia 26 weeks after surgery by radiology and histologically after
      euthanasia. The presence of human cells after xenogenic transplantation was
      analyzed using human-specific in situ hybridization. Both radiology and histology
      demonstrated significantly better bone formation after transplantation of
      autologous ovine MSCs on mineralized collagen compared with unloaded matrices and
      with the xenogenic treatment group. Nevertheless, no local or systemic rejection
      reactions could be observed after transplantation of human MSCs, although the
      presence of human MSCs could be demonstrated. It can be concluded that despite
      successful demonstration of the presence of human MSCs after xenogenic
      transplantation, the xenogenic transplantation of human MSCs leads to poorer bone
      regeneration than autologous transplantation of ovine MSCs.

PMID- 19604041
TI  - Regenerative medicine glossary.

PMID- 19604040
TI  - Producing recombinant adeno-associated virus in foster cells: overcoming
      production limitations using a baculovirus-insect cell expression strategy.
AB  - Establishing pharmacological parameters, such as efficacy, routes of
      administration, and toxicity, for recombinant adeno-associated virus (rAAV)
      vectors is a prerequisite for gaining acceptance for clinical applications. In
      fact, even a therapeutic window, that is, the dose range between therapeutic
      efficacy and toxicity, has yet to be determined for rAAV in vivo. Multiphase
      clinical trials investigating the safety and efficacy of recombinant AAV-based
      therapeutics will require unprecedented vector production capacity to meet the
      needs of preclinical toxicology studies, and the progressive clinical protocol
      phases of safety/dose escalation (phase I), efficacy (phase II), and high
      enrollment, multicenter evaluations (phase III). Methods of rAAV production
      capable of supporting such trials must be scalable, robust, and efficient. We
      have taken advantage of the ease of scalability of nonadherent cell culture
      techniques coupled with the inherent efficiency of viral infection to develop an
      rAAV production method based on recombinant baculovirus-mediated expression of
      AAV components in insect-derived suspension cells.

PMID- 19604042
TI  - INSM1 promoter-driven adenoviral herpes simplex virus thymidine kinase cancer
      gene therapy for the treatment of primitive neuroectodermal tumors.
AB  - The INSM1 gene encodes a developmentally regulated zinc finger transcription
      factor. INSM1 expression is normally absent in adult tissues, but is reactivated
      in neuroendocrine tumor cells. In the present study, we analyzed the therapeutic
      potential of an adenoviral INSM1 promoter-driven herpes simplex virus thymidine
      kinase (HSV-tk) construct in primitive neuroectodermal tumors (PNETs). We
      constructed an adenoviral INSM1 promoter-driven HSV-tk gene for therapy in PNETs.
      The PNET-specific adeno-INSM1 promoter HSV-tk construct was tested both in vitro
      and in vivo in a nude mouse tumor model. Northern blot analysis and transient
      transfection of an INSM1 promoter-driven luciferase reporter gene indicated that
      the INSM1 promoter was active in neuroblastoma (IMR-32), retinoblastoma (Y79),
      and medulloblastoma (D283 Med) cells, but not in glioblastoma (U-87 MG) cells.
      After Ad-INSM1p-HSV-tk infection, the levels of HSV-tk protein expression were
      consistent with INSM1 promoter activities. Furthermore, in vitro multiplicity of
      infection and ganciclovir (GCV) sensitivity studies indicated that the INSM1
      promoter could mediate specific expression of the HSV-tk gene and selective
      killing of INSM1-positive PNETs. In vivo intratumoral adenoviral delivery
      demonstrated that the INSM1 promoter could direct HSV-tk gene expression in a
      nude mouse tumor model and effectively repressed tumor growth in response to GCV
      treatment. Taken together, our data show that the INSM1 promoter is specific and
      effective for targeted cancer gene therapy in PNETs.

PMID- 19604044
TI  - Rotavirus induces a biphasic enterotoxic and cytotoxic response in human-derived
      intestinal enterocytes, which is inhibited by human immunoglobulins.
AB  - The mechanisms of diarrhea due to rotavirus infection in humans are not fully
      understood; no specific therapy is available, but orally administered human serum
      immunoglobulins are effective in blocking stool output. We aimed to investigate
      the effect of rotavirus on ion transport and the role of NSP4 in human-derived
      enterocytes, and to test the efficacy of human serum immunoglobulin in a model of
      rotavirus infection. Soon after infection, rotavirus induces active chloride
      secretion in enterocytes. This effect is evident before viral replication leads
      to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents
      the early secretory phase but not cell damage. Incubation with human serum
      immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an
      early NSP4-dependent ion secretion and subsequent tissue damage. The combined
      enterotoxic and cytotoxic effects may be responsible for the increased severity
      of diarrhea due to rotavirus infection, and both are counteracted by human serum
      immunoglobulin.

PMID- 19604045
TI  - Slow accumulation of HIV resistance mutations: implications for resource-limited
      settings?

PMID- 19604043
TI  - Rate of accumulation of thymidine analogue mutations in patients continuing to
      receive virologically failing regimens containing zidovudine or stavudine:
      implications for antiretroviral therapy programs in resource-limited settings.
AB  - BACKGROUND: Because changes in antiretroviral therapy in resource-limited
      settings (RLSs) are delayed until patients experience immunological or clinical
      failure, it is important to be able to estimate the consequences in terms of
      accumulation of thymidine analogue (TA) mutations (TAMs). METHODS: The study
      included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs)
      (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure
      between tests), provided that the first GRT was performed after the first
      virological failure of a TA and that the same TA was continued until the second
      GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after
      virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in
      65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person
      years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years).
      Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1
      [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor
      (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV
      infection through heterosexual (vs homosexual) contacts were associated with a
      faster rate of TAM accumulation. CONCLUSIONS: Although the estimated rate of TAM
      accumulation was lower than anticipated, all possible efforts should be continued
      to increase the availability of drug options in RLSs.

PMID- 19604046
TI  - Intestinal Enterococcus faecium colonization improves host defense during
      polymicrobial peritonitis.
AB  - BACKGROUND: Vancomycin-resistant (VR) Enterococcus faecium is increasingly found
      to colonize and infect hospitalized patients. Enterococci are frequently isolated
      from polymicrobial infections originating from the intestines. The impact of VR
      E. faecium on these infections and vice versa is not clear. METHODS: Mice were
      intestinally colonized with VR E. faecium during oral vancomycin treatment;
      control mice received oral vancomycin only. Fourteen days later, cecal ligation
      and puncture (CLP) was performed in all mice to induce polymicrobial peritonitis
      in the presence or absence of VR E. faecium colonization. RESULTS: VR E. faecium
      colonization per se was not associated with systemic dissemination of VR E.
      faecium. CLP resulted in systemic VR E. faecium infection in all VR E. faecium
      colonized mice, with high VR E. faecium loads in peritoneal lavage fluid, blood,
      liver, and lungs. Forty-eight hours after CLP, mice infected with VR E. faecium
      had significantly lower bacterial loads in all organs tested than mice not
      infected with VR E. faecium. Additionally, lower inflammatory parameters were
      measured in VR E. faecium-infected mice. CLP induced transient liver and kidney
      damage, with a faster recovery in VR E. faecium-colonized mice. CONCLUSIONS: VR
      E. faecium infection, originating from a natural source (the intestinal tract),
      does not worsen the outcome of CLP-induced polymicrobial peritonitis and sepsis
      but rather facilitates bacterial clearance and attenuates host inflammatory
      responses.

PMID- 19604047
TI  - A point mutation in the agr locus rather than expression of the Panton-Valentine
      leukocidin caused previously reported phenotypes in Staphylococcus aureus
      pneumonia and gene regulation.
AB  - sThe role of Panton-Valentine leukocidin (PVL) in Staphylococcus aureus
      pathogenesis is controversial. Here, we show that an unintended point mutation in
      the agr P2 promoter of S. aureus caused the phenotypes in gene regulation and
      murine pneumonia attributed to PVL by earlier investigators. In agreement with
      other studies that failed to detect similar effects of PVL using community
      associated methicillin-resistant S. aureus strains, we found no significant
      effect of PVL on gene expression or pathogenesis after we repaired the mutation.
      These findings provide further evidence that PVL does not have a major impact on
      S. aureus pathogenesis. Moreover, our results demonstrate that a single
      nucleotide polymorphism in an intergenic region can dramatically affect bacterial
      physiology and virulence. Finally, our work emphasizes the need to frequently
      evaluate the integrity of the S. aureus agr locus.

PMID- 19604048
TI  - New developments with vancomycin-resistant enterococci: E. faecium--friend or
      foe?

PMID- 19604050
TI  - Aerosol dynamics and health: strategies to reduce exposure and harm.
AB  - The term 'air pollution' is used to describe the presence of chemicals or
      materials in the atmosphere that produce poor air quality. Air pollutants may be
      classified into four principal categories which include anthropogenic (man-made;
      e.g. combustion products), biogenic (biological; e.g. pollen, allergens),
      technogenic (technology; e.g. metal aerosols or smelter) and geogenic
      (geological; e.g. erosion of earth, i.e. minerals, volcanic ash). From these
      categories are derived the seven main pollutants of human health concern, i.e.
      carbon monoxide, nitrogen dioxide, ozone, sulphur dioxide, hydrocarbons, lead,
      and particulate matter (PM). The common provenance of all these emissions is from
      the combustion of fossil fuels (e.g. coal, petrol and diesel), biomass (e.g.
      cooking) and tobacco smoke. PM is now considered to be the most precarious of
      pollutants, with the combustion-derived nano-particles being linked to a myriad
      of premature and excess deaths world-wide; especially for persons with pre
      existing cardiovascular disorders. This meeting intended to bring together
      scientists from a host of disciplines (toxicologists, biologists, chemists,
      physicists and material scientists) that work at the bio-particulate interface.
      It aimed to present and discuss, via topical 'break-out' sessions, the current
      thoughts on the 'burden to human health' following exposure to and harm from
      combustion-derived particles. Furthermore, strategies for 'harm reduction' were
      another feature of this cross-disciplinary meeting. The final objectives were to
      identify biomarkers of exposure and harm to these inhalation hazards. All topics
      covered sought to find biomarker indices for human health effects.

PMID- 19604051
TI  - London air quality: a real world experiment in progress.
AB  - London currently has the highest nitrogen dioxide (NO2) concentration recorded
      for any European city and for particulate matter (PM) it has some of the worst
      hot spots. Therefore overall, for these two pollutants, London is the worst in
      the UK and amongst the worst in Europe. Exposure to elevated concentrations of
      air pollutants such as PM and NO2 has well-established heath effects and most
      countries now have strict guidelines for air quality. London's air quality
      problems are driven largely by traffic. This, along with the high density of
      people in an urban area results in air quality guidelines being exceeded on a
      regular basis and large numbers of people being affected. In an attempt to combat
      London's air quality problems the Mayor of London introduced a series of measures
      to decrease traffic emissions. These included both a restriction on the number of
      vehicles entering central London each day--the Congestions Charging Scheme (CCS),
      and the discouragement of the most polluting heavy goods vehicles from entering-
      the London Low Emission Zone (LEZ). Together, it is hoped that these measures
      will lead to an improvement in air quality and provide a direct health benefit to
      Londoners. Research underway is charting the progress of this real world
      experiment.

PMID- 19604052
TI  - Airborne emissions in the harbour and port of Cork.
AB  - It is now accepted that the transport sector is responsible for a large and
      growing share of global emissions affecting both health and climate. The
      quantification of these effects requires, as an essential first step, a
      comprehensive analysis and characterization of the contributing subsectors, i.e.
      road transport, shipping, aviation and rail. The shipping contribution in
      dock/harbour areas is of particular interest because many vessels use old engines
      powered with old technology giving rise to high levels of particulate emissions
      mainly because the fuel employed contains high levels of sulphur, up to 4.5%.
      Large amounts of polyaromatic hydrocarbons and varying contents of transition
      metals are also detected. Few studies on the physicochemical composition of
      direct emissions from ship fuels have been performed; none have been compared to
      actual contents in local harbour or port atmospheres. The transformation of these
      ship-related materials to toxicologically active species may be much more
      efficient than corresponding road emission or domestic sources because of the
      expected highly acidic nature of the particulates. Surface, toxic material may
      therefore become readily bioavailable under such conditions but such studies have
      not been performed hitherto. This mini-review outlines in detail the issues
      raised above in the context of measurements made in Cork, Ireland.

PMID- 19604053
TI  - Identification of chemical tracers in the characterisation and source
      apportionment of inhalable inorganic airborne particles: an overview.
AB  - The acquisition of increasingly large analytical datasets from standardized air
      pollution monitoring stations allows more effective characterization of the fine
      aerosol cocktail breathed daily by modern urban populations. It is increasingly
      clear from such data that there is great variability in the chemical composition
      of inorganic inhalable particulate matter (PM10 = < 10 microm in size) in both
      space and time. Such variability can be demonstrated using selected tracer
      elements which, combined with source apportionment techniques, allow
      differentiation between natural (geological) and anthropogenic sources such as
      traffic and various industries. These tracer elements, which are commonly toxic
      metals, can be shown to concentrate in the finer, more deeply inhalable PM
      fraction, and are thus linked to potential inflammation and oxidative stress
      after inhalation. Legislation concerned only with measuring physical PM mass
      concentrations therefore fails to address potential health effects linked to
      chemical variations in ambient aerosols.

PMID- 19604054
TI  - Sources and source contributions to fine particles.
AB  - Fine dust is currently seen is one of the major issues in air quality as being
      responsible for causing negative health effects. Hence it is important to derive
      information on particle sources and their contribution to the ambient
      concentrations. This paper reviews two recent studies related to fine particle
      sources in Germany. The first study deals with the attribution of source regions
      to PM10 mass concentrations in nine agglomeration areas of Germany. The second
      study focuses on the diffusive sources from traffic differentiating and
      quantifying the various non-exhaust related emissions at an Autobahn.

PMID- 19604055
TI  - Future European emission standards for vehicles: the importance of the UN-ECE
      Particle Measurement Programme.
AB  - Traffic-related emissions of fine particles represent one of the main sources of
      air pollution especially in urban areas. In particular, diesel engines are blamed
      as one of the main contributors for their inherent high particulate emissions. In
      order to reduce the impact on human health of particulate emissions from
      vehicles, new stricter emission standards were considered necessary for Europe.
      The introduction of very low particulate emission limits has required the
      development of an improved measurement procedure for particulate mass and a new
      measurement procedure for particle number. The Particle Measurement Programme
      (PMP) was established in 2001 on the initiative of some European states to
      achieve this target. The interlaboratory comparison exercise for light duty
      vehicles, co-managed by the Joint Research Centre (JRC) of the European
      Commission and the UK Department of Transport, was completed in 2007, and the
      results have provided the scientific basis for the new Euro 5/6 limits for
      particle number and particulate mass. The heavy-duty interlaboratory exercise was
      started in the second half of 2007 with an exploratory work carried out at the
      JRC and is still on-going.

PMID- 19604056
TI  - Ambient air particulate matter PM10 and PM2.5: developments in European
      measurement methods and legislation.
AB  - The measure of airborne particulate matter PM10 is effectively defined for
      European regulatory purposes by the European Committee for Standardisation (CEN)
      standard EN 12341:1998--a gravimetric filter-based method. However, compared with
      the reference methods written for other pollutants, specifically to address the
      needs of the Air Quality Directives, EN 12341 falls short in areas such as
      ongoing Quality Assurance and Quality Control. Also, scientific knowledge about
      PM has moved on considerably since 1998, so that we now realize that
      implementations of variations allowed within EN 12341:1998 can lead to
      substantial differences in results obtained. These issues were partially
      addressed within the CEN standard for PM2.5, EN 14907:2005, which, for example,
      included tighter control of the handling of sampled filters to reduce losses of
      semi-volatile material. CEN Technical Committee 264 Working Group 15 is currently
      revising EN 12341, and has the opportunity to improve the reference method
      further, for example by tighter specification of the filter material, or by
      changing the specification for the humidity at which the filters are brought to
      equilibrium. Any changes must, however, be considered in the context of the
      regulatory implications of the standard, so that improvements in scientific
      quality must be balanced with the effect of a step change in reference method,
      and with associated costs. The paper outlines the present position of the EN
      12341 revision and recent changes to EU Air Quality legislation.

PMID- 19604057
TI  - Daily measurement of organic compounds in ambient particulate matter in Augsburg,
      Germany: new aspects on aerosol sources and aerosol related health effects.
AB  - Several epidemiological studies have shown that in the human population ambient
      particulate matter (PM) is associated with adverse health effects. Little is
      known, however, about the relative effects of aerosol constituents. Since 2002,
      diurnal samples of ambient PM2.5 were analysed by automated methods for the
      quantification of particle-associated organic compounds (POC). Data on chemical
      composition have been investigated in epidemiological and biological effect
      studies. As a result of these studies, the associations found between PAH
      concentration and symptoms of myocardial infarction survivors suggest a major
      influence of combustion sources on cardiovascular health effects. The
      correlations found between formation of reactive oxygen species and the presence
      of specific organic compounds suggests an important influence of biomass
      combustion particles in PM2.5-associated oxidative stress.

PMID- 19604058
TI  - The geochemistry and bioreactivity of fly-ash from coal-burning power stations.
AB  - Fly-ash is a byproduct of the combustion of coal in power stations for the
      generation of electricity. The fly-ash forms from the melting of incombustible
      minerals found naturally in the coal. The very high coal combustion temperatures
      result in the formation of microscopic glass particles from which minerals such
      as quartz, haematite and mullite can later recrystallize. In addition to these
      minerals, the glassy fly-ash contains a number of leachable metals. Mullite is a
      well-known material in the ceramics industry and a known respiratory hazard.
      Macroscopically mullite can be found in a large range of morphologies; however
      microscopic crystals appear to favour a fibrous habit. Fly-ash is a recognized
      bioreactive material in rat lung, generating hydroxyl radicals, releasing iron,
      and causing DNA damage. However, the mechanisms of the bioreactivity are still
      unclear and the relative contributions of the minerals and leachable metals to
      that toxicity are not well known.

PMID- 19604059
TI  - Characterization and bioreactivity of respirable airborne particles from a
      municipal landfill.
AB  - With an increasing population and greater pressure on land-use, the possible
      problems of landfilling are of increasing concern. These concerns include the
      possible adverse health effects arising from living in the vicinity of municipal
      solid waste (MSW) landfills. Human exposure to potential landfill emissions by
      respiratory, gastrointestinal or dermal mechanisms warrants further
      investigation. PM10 and PM2.5 from a UK landfill were physicochemically
      characterized and their bioreactivity screened by a plasmid scission assay in
      comparison with an urban PM collection. Preliminary data from human toxicology
      pathway-specific microarrays indicate landfill PM10 presents a comparable
      geobiological insult to urban PM10 in a human tracheobronchial tissue model.

PMID- 19604060
TI  - Deposition of aerosol particles in human lungs: in vivo measurement and
      modelling.
AB  - The deposition dose and site of inhaled particles within the lung are the key
      determinants in health risk assessment of particulate pollutants. Accurate dose
      estimation, however, is a formidable task because aerosol transport and
      deposition in the lung are governed by many factors whose precise workings are
      often not fully understood. In vivo human data obtained under controlled
      environment are most important and provide the primary basis of estimating lung
      doses. The existing database, however, is not sufficient to cover widely varying
      exposure conditions encountered during daily activities. Mathematical models thus
      are used to fill the gap or to extend the range of experimental data and are
      further used as a tool for analysing the exposure-dose relationship under varying
      inhalation conditions. In this report we briefly review and discuss our recent
      studies of in vivo measurement of inhaled particles in normal subjects,
      subsequent analysis of the data for empirical modelling and an improved
      mathematical model that can be used for a wide range of applications.

PMID- 19604061
TI  - Modelling particle deposition in human lungs: modelling concepts and comparison
      with experimental data.
AB  - Deposition of inhaled particles in the human lung is determined by biological
      factors, such as lung morphology and respiratory physiology, as well as by
      physical factors, such as fluid dynamics of the inhaled air and physical
      deposition mechanisms acting upon inhaled particles. Different conceptual
      particle deposition models vary primarily with respect to lung morphometry and
      mathematical modelling technique, rather than by using different deposition
      equations. Current whole lung deposition models permit the prediction of particle
      deposition in single airway generations or defined regions of the human lung for
      any combination of particle size and breathing pattern. Although comparisons with
      experimental data in human subjects indicate that all presently available
      deposition models correctly predict total and regional deposition, they cannot be
      validated by comparison with experimental data at the single airway or airway
      generation level.

PMID- 19604063
TI  - Dosimetry and toxicology of inhaled ultrafine particles.
AB  - Both epidemiological and toxicological studies indicate that inhalation and
      subsequent deposition of airborne particles into the lungs have adverse health
      effects. Recently, the ultrafine particle (UfP) fraction (diameter < 100 nm) has
      received particular attention, as their small size may lead to more toxic
      properties. In this study we summarize the current knowledge on the dosimetry of
      inhaled particles (including UfPs) with a focus on recent data on translocation
      of UfPs into secondary target organs (such as brain and heart) suggesting that
      the lifetime dose of ambient UfPs in secondary target organs is about 10(11)
      particles. Furthermore, we highlight the main pathways of particle induced
      toxicity and the reasons for the potentially higher toxicity of UfPs. Finally, we
      discuss recent evidence indicating that (BET) surface area is the single most
      relevant dose metric for the toxicity of UfPs, which has important implications
      for regulatory measures on the toxicity of ambient and engineered particles.

PMID- 19604062
TI  - Dosimetry considerations for animal aerosol inhalation studies.
AB  - The determination of the dose of inhaled aerosol particles in animal subjects is
      not a trivial exercise. In its simplest form, the dose is the amount (particle
      number, mass or other relevant metric) that deposits in the respiratory tract.
      The amount deposited will depend on the aerosol particle sizes (e.g. the
      aerodynamic diameter size distribution), the duration of exposure, the exposure
      system's delivery efficiency, the subject's ventilation rate, the species and
      strain, and other factors. Similarly, species differences in the clearance rates
      of deposited particles will influence the time integrated particle doses. In
      practice, particle doses are estimated using mathematical models, previous
      experimental dosimetry data, tracers of the inhaled particles and biomarkers of
      exposure. With care, desired aerosol doses can be achieved and documented.

PMID- 19604064
TI  - Residential traffic exposure and coronary heart disease: results from the Heinz
      Nixdorf Recall Study.
AB  - Traffic is one of the major sources of environmental pollution in metropolitan
      areas, emitting pollutants such as particulate matter and noise. Epidemiological
      evidence links both particulate matter (PM) and noise to cardiovascular disease
      and increased cardiovascular mortality. Short-term exposure to traffic may
      trigger acute cardiovascular events. Long-term residential traffic exposure is
      associated with the degree of subclinical atherosclerosis, prevalence of coronary
      heart disease and incidence of myocardial infarction. This review will present
      recent epidemiological findings regarding long-term exposure to traffic and its
      association with coronary heart disease, using results from the Heinz Nixdorf
      Recall Study, an ongoing prospective cohort study of 4814 unselected participants
      living in three large adjacent cities of the highly industrialized Ruhr Area in
      western Germany. Special focus is placed on the association of long-term traffic
      exposure with subclinical atherosclerosis, the major underlying pathology for
      cardiovascular disease.

PMID- 19604065
TI  - Smokeless tobacco: the epidemiology and politics of harm.
AB  - The health burden from tobacco smoking results almost entirely from inhalation of
      the components of smoke, although this is not widely known. The primary benefit
      of smoking is nicotine delivery, but nicotine can be obtained without combustion.
      Thus there is potential for tobacco harm reduction (THR), the substitution of
      lower-risk nicotine products for smoking. Epidemiological evidence suggests that
      smokeless tobacco causes about one one-hundredth the health risk of smoking.
      Despite the practice of harm reduction being widely accepted in public health,
      however, THR has faced fierce opposition from antitobacco activists. These
      activists have effectively misled the public about what aspect of smoking
      cigarettes causes the harm, convincing them that nicotine and tobacco themselves
      are harmful, ignoring the smoke. In the interests of promoting public health and
      rescuing science from politics, experts on inhalation hazards and health could
      play an important role in educating the public and policy makers about THR.

PMID- 19604066
TI  - Smokeless tobacco: a gateway to smoking or a way away from smoking.
AB  - Recently, tobacco companies have been marketing moist smokeless tobacco products
      that are 'spitless'. These products have lower concentrations of tobacco-specific
      nitrosamines and of other harmful chemicals than other tobacco products, but can
      deliver relatively high doses of nicotine. They are packaged in small sachets,
      similar to tea bags that are placed between cheek and gum. Global promotion of
      smokeless tobacco products is hotly debated among tobacco control and public
      health experts. Proponents point to the Swedish experience where snus (Swedish
      moist snuff) is widely used as an alternative to cigarette smoking among men.
      Meanwhile, Sweden has low rates of smoking and a lower rate of respiratory
      diseases and lung cancers by comparison to other developed countries. The
      opponents argue that snus has its own risks, that no form of tobacco should ever
      be promoted; and that 'snus is culture-bound and not transferable to other
      settings'. Critics also suspect that the tobacco industry will use snus marketing
      as a 'gateway' to promote cigarettes among young people. Research on the effects
      of marketing snus to smokers is too limited to support using snus as a harm
      reduction tool, and the epidemiological data are not conclusive.

PMID- 19604067
TI  - The role of oxidative stress in the biological responses of lung epithelial cells
      to cigarette smoke.
AB  - The mechanism(s) by which cigarette smoke contributes to lung diseases, such as
      cancer, remains unclear. Recent developments in our knowledge of cell signalling
      events suggest that cigarette smoke causes oxidative stress and proinflammatory
      responses in cells of the lung. Cigarette smoke is a complex mixture of over 4000
      compounds and high levels of oxidants and reactive oxygen species (ROS) have been
      detected in both mainstream and sidestream smoke. Oxidative stress that ensues,
      when the antioxidant defences are depleted, is accompanied by increases in ROS
      production in lung epithelial cells. Cigarette smoke-mediated oxidative stress
      produces DNA damage and activates survival signalling cascades resulting in
      uncontrolled cell proliferation and transformation. Intervention studies using
      antioxidants have provided compelling evidence that oxidative stress plays a
      critical role in the aetiology of smoking-related disorders.

PMID- 19604068
TI  - Early life insult from cigarette smoke may be predictive of chronic diseases
      later in life.
AB  - Evidence is rapidly accumulating that links cigarette smoke (CS) exposure in
      utero with the development of a variety of disease pathologies in the older
      offspring including, type 2 diabetes, obesity, certain childhood cancers and
      respiratory disorders. The role that the fetal environment plays in these late
      onset outcomes and the underlying cellular/molecular mechanisms by which these CS
      induced effects may occur are currently unknown. Although we are becoming more
      aware of the fact that prenatal insult can underlie childhood/adult diseases,
      critical knowledge gaps still exist including gene-environment interactions, and
      how a CS-induced imbalance in immune dynamics (i.e. TH1/TH2) might affect asthma
      development and/or exacerbation later in life. In this mini-review we introduce
      the concept of sexual dimorphism in CS-induced late-onset disease outcomes, as
      well as explore the mechanisms by which CS exposure in utero can lead to
      cardiovascular, cancer and respiratory abnormalities in the exposed offspring. By
      addressing such questions using animal models, appropriate intervention
      strategies can be developed that will help to protect children's health and their
      long-term quality of life.

PMID- 19604069
TI  - Break-out sessions report.

PMID- 19604070
TI  - Promoted adipogenesis of rat mesenchymal stem cells by transfection of small
      interfering RNA complexed with a cationized dextran.
AB  - The objective of this study is to investigate the possibility of small
      interfering RNA (siRNA) complexed with a cationized dextran of nonviral carrier
      to biologically modify the adipogenesis extent of bone marrow-derived mesenchymal
      stem cells (MSC). Spermine was chemically introduced to the hydroxyl groups of
      dextran to prepare the cationized dextran (spermine-dextran). The spermine
      dextran could form a complex with siRNA, and the physicochemical properties were
      changed by the molecular weight of dextran, the molar percentage of spermine
      introduced to dextran, and the molar ratio of nitrogen molecule of spermine
      dextran to the phosphorous ones of siRNA (N/P ratio). The gene expression level
      of luciferase or green fluorescence protein was significantly suppressed by
      transfection with the complex of spermine-dextran and siRNA. The gene expression
      level by the complex decreased with an increase in the extent of complex
      internalized. Biochemical experiments revealed that culture in an adipogenic
      differentiation medium allowed MSC to differentiate into adipogenic cells.
      However, upon culturing with siRNA of anti-transcription coactivator containing
      PDZ-binding motif (TAZ) for osteogenic differentiation complexed with the
      spermine-dextran, the adipogenesis of MSC was further promoted. It is concluded
      that the spemine-dextran was a promising nonviral carrier to suppress the
      expression level of differentiation gene, resulting in the modification of cell
      differentiation direction.

PMID- 19604071
TI  - Temporal analysis of equine bone marrow aspirate during establishment of putative
      mesenchymal progenitor cell populations.
AB  - Mesenchymal progenitor cells (MPCs) are often characterized using surface markers
      after expansion and treatment in culture. There are no studies directly comparing
      gene and protein markers in undifferentiated samples during the very early phases
      of culture. The goal of this study was to evaluate temporal gene and protein
      expression changes during establishment of equine MPC cultures. Bone marrow
      aspirate was obtained from 35 horses and processed by density gradient
      centrifugation. In freshly isolated bone marrow, mononuclear cells had variable
      expression of CD44, CD11a/CD18, CD90, and CD45RB cell surface molecules. After 2
      h of culture, bone marrow mononuclear cells had a phenotype of CD44(hi),
      CD29(hi), CD90(lo), CD11a/CD18(hi), and CD45RB(lo). Isolated mononuclear cells
      were analyzed by flow cytometry and RT-qPCR at 2, 7, 14, 21, and 30 days of
      culture. At all culture time points, gene expression was in agreement with cell
      surface protein expression. In established cultures of MPCs, cells remained
      robustly positive for CD44 and CD29. The proportion of positive cells and the
      mean fluorescence intensity of positive cells increased in CD90 expression as MPC
      cultures became more homogeneous. Inversely, the population of cells in culture
      decreased expression of CD11a/CD18 and CD45RB molecules over time. The decreased
      expression of the latter molecules makes these useful negative markers of
      established MPC cultures under normal expansion conditions. The results of this
      study demonstrate numerous dynamic changes in cell surface molecule expression
      during early establishment of MPC populations, which may aid to improve MPC
      isolation methods for research or therapeutic applications.

PMID- 19604072
TI  - Cell size but not genome size affects scaling of metabolic rate in eyelid geckos.
AB  - The metabolic theory of ecology (MTE) predicts the ubiquity of the of 3/4 scaling
      exponent relating metabolic rate (MR) to body mass, as well as cell-size
      invariance coupled with body-size dependence of cellular MR in quickly dividing
      cells. An alternative prediction is that MR scales interspecifically with a
      coefficient that is between 2/3 and 1, depending on the cell size and cell MR,
      which is mostly driven by the cell surface-to-volume ratio. We tested (1) the
      contribution of cell size to interspecific differences in MR and (2) whether the
      cell size-MR relationship is mediated by genome size (GS), which usually
      correlates positively with cell size. We tested (1) and (2) using erythrocyte
      area as a proxy for cell size in 14 eyelid geckos, which belong to a monophyletic
      group exhibiting large body-size variation. The scaling of standard MR (SMR) was
      significantly lower than 3/4, whereas mass-specific SMR correlated with
      erythrocyte area in both phylogenetically adjusted and conventional analyses.
      This points to cell-size variation as the factor governing metabolic rate
      scaling, which questions predictions of the MTE. However, the nonsignificance of
      the correlation between mass-specific SMR and GS undermines the strength of the
      relation between GS and cell size, at least in these species.

PMID- 19604073
TI  - Clinical and resource-use outcomes of risperidone long-acting injection in recent
      and long-term diagnosed schizophrenia patients: results from a multinational
      electronic registry.
AB  - BACKGROUND: Non-adherence to pharmacological treatment leading to frequent
      relapses and rehospitalizations is a major issue of concern among schizophrenia
      patients, especially those who are recently diagnosed. Risperidone long-acting
      injection (RLAI) has been shown to be efficacious, improve compliance, and
      increase long-term retention rate on therapy. OBJECTIVE: To determine clinical
      outcomes and hospitalizations before and after the initiation of RLAI among
      schizophrenia patients with recent (< or =2 years) diagnosis relative to those
      who had long-term (> 2 years) diagnosis. RESEARCH DESIGN AND METHODS: The
      electronic Schizophrenia Treatment Adherence Registry (e-STAR) is an
      observational study of patients with schizophrenia who start treatment with RLAI.
      Data were recorded at baseline, retrospectively for the 12 months prior to
      baseline, and prospectively every 3 months for 24 months. Data on patients with a
      defined length of diagnosis were pooled from eight countries. MAIN OUTCOME
      MEASURES: Clinical Global Impression of Illness Severity (CGI-S), Global
      Assessment of Functioning (GAF) scores, and hospitalization data were key
      outcomes. RESULTS: The magnitude of improvement in CGI-S scores was greater in
      the recent versus long-term diagnosis group [Delta -1.48 vs. Delta -0.95 (12
      months); Delta -1.6 vs. Delta -1.09 (24 months)]. There were parallel
      improvements in GAF scores [Delta 19.4 vs. Delta 13.7 (12 months); Delta 22.3 vs.
      Delta 16.8 (24 months)]. The decline in the proportion of patients hospitalized
      from the retrospective to the prospective period was greater in the recent versus
      long-term diagnosis group (Delta -36.0 vs. Delta -19%, respectively) at 12
      months. This was also true for the number of hospital stays (Delta -0.6 vs. Delta
      -0.3, respectively) and length of stay (days) (Delta -20.9 vs. Delta -6.9,
      respectively) at 12 months. Common adverse events in both groups included
      psychiatric, gastrointestinal, musculoskeletal and reproductive system and breast
      disorders. CONCLUSIONS: Treatment with RLAI is associated with improved outcomes
      in recently diagnosed and chronic patients. However, the magnitude of improvement
      was higher in recently diagnosed patients.

PMID- 19604074
TI  - Dissociation, trauma, affect regulation and personality in patients with a
      borderline personality organization.
AB  - While the association between dissociation and trauma has been the subject of
      intensive research, the relationship between dissociation, childhood trauma, and
      personality characteristics has not yet been explored in detail. Fifty two
      patients suffering from a personality disorder completed the Dissociative
      Experiences Scale, the Childhood Trauma Questionnaire, and the personality and
      affect regulation measurement instruments SWAP and AREQ. Results are critically
      discussed within a psychoanalytic framework, which should also help clarify the
      rather vague concept of dissociation.

PMID- 19604075
TI  - Slippery when wet: the imperfect art of interpretation.
AB  - When pursuing a line of psychoanalytic interpretation, there are many factors
      that need to be considered. Interpretation is always a provisional exercise in
      which the analyst's proposes something to the patient to consider and then wait
      to see his or reaction. Whether or not the interpretation is correct is not as
      important as the patient's reaction to it. Does it cultivate insight, does it
      spur defensive reactions, does it feel helpful, does it leave the patient hurt or
      misunderstood, or does it aid the patient in facing their anxieties and exploring
      them in a way that might facilitate change? These are just some of the
      possibilities when analysts voice their opinions about what might be happening at
      an unconscious level in a patient's immediate experience. Interpretations may be
      correct and address the patient's phantasies and transference state, but they can
      also be part of a pathological projective identification system. In other words,
      it can be a collusive acting out that not only helps patients to grow but also
      serves their defensive structure and thus helps them to retreat at the same time.
      The author explores clinical moments in which interpretive enactment or
      interpretive acting out occur. The constantly shifting emotional states produced
      by transference, countertransference, and the dynamics of projective
      identification make the interpretive process prone to instability, fallibility,
      and uncertainty. The unavoidable pros and cons of interpretive acting out are
      examined through the lens of one complex psychoanalytic treatment.

PMID- 19604076
TI  - Rorschach assessment of reality testing, affect and object representation of
      borderline pathology: a comparison of clinical samples.
AB  - This study examines the personality functioning of outpatients diagnosed with
      borderline pathology (BP) compared to a nonborderline pathology Axis I clinical
      control group (NonBP). Interrater reliability for all variables was in the good
      or excellent range. Significant differences were found examining Rorschach
      variables assessing dysphoric affect and affect regulation/experiencing with BP
      when compared to the Axis I group. Additionally, individuals with BP had more
      malevolent object representations than individuals with only Axis I disorders.
      The clinical implications of these findings with regard to borderline pathology
      are discussed.

PMID- 19604078
TI  - A lentiviral vector that activates latent human immunodeficiency virus-1
      proviruses by the overexpression of tat and that kills the infected cells.
AB  - Despite the efficient HIV-1 replication blockage achieved with current highly
      active antiretroviral therapy (HAART) therapies, HIV-1 persists in the body and
      survives in a latent state that can last for the entire life of the patient. A
      long-lived reservoir of latently infected CD4(+) memory T cells represents the
      most important sanctuary for the virus and the greatest obstacle for viral
      eradication. In this work, we present an initial step toward a gene therapy
      approach aimed at the activation of latent provirus to induce the death of
      latently infected T cells. Latent HIV-1 infection is characterized by the failure
      of viral gene expression as a consequence of uninitiated or aborted
      transcription. We have constructed an HIV-1-based lentiviral vector (p5p53RTAT3)
      that expresses the viral trans-activating protein Tat in a drug-regulated manner
      and p53 in a Rev-dependent manner. We have demonstrated that the Tat-expressed
      protein from p5p53RTAT3 vector reactivates latent HIV-1 proviruses in J1.1 and
      ACH-2 cell lines and promotes p53-induced apoptosis in the presence of Rev. Our
      system was able to trigger the trans-activation of the provirus 5' long terminal
      repeat (LTR), stimulate the expression of the Rev protein from a tat-defective
      provirus, and provoke apoptosis selectively in the cells transfected with a tat
      defective HIV-1 provirus in contrast to those with no HIV-1 provirus. However,
      the Rev-dependent p53 killing of latently infected cells was not effective enough
      for complete elimination of the awakened HIV-1 viruses. In summary, we have
      developed a vector system that is efficient in activating latent HIV-1 proviruses
      but that needs further improvement to kill infected cells.

PMID- 19604079
TI  - Epigenetic and microRNA-dependent control of cytochrome P450 expression: a gap
      between DNA and protein.
AB  - Although pharmacogenetics has been instrumental in describing interindividual
      variations in drug metabolism, epigenetic factors offer another blanket of
      information that could give a more vivid picture and help in developing a more
      personalized therapy. The dynamic aspect of epigenetics could likewise provide
      more definite answers to the role of changing environmental factors in drug
      response: the bridge that connects the environment to the genome. In this review
      we discuss known epigenetic and microRNA-dependent regulation of the human drug
      metabolizing cytochromes P450 to help explain the unknown factors of variable
      drug response.

PMID- 19604080
TI  - Back to the future: why randomized controlled trials cannot be the answer to
      pharmacogenomics and personalized medicine.
AB  - Randomized controlled trials are the gold standard for determining the efficacy
      of therapeutic interventions. However, medical practice has not evolved around
      the concept of randomized trials, but around the idea of careful observations,
      (anecdotal) case studies and the evaluation of retrospective data. Interventions
      discovered by these means and taken forward into clinical practice became
      standard practice as they continued to be superior when compared with prior or
      alternative types of treatment. Personalized medicine refers to an approach of
      clinical practice where a particular treatment is not chosen based on the
      'average patient', but on characteristics of an individual patient, for example,
      a genetic profile that may vary from one patient to another, and therefore,
      allows to 'personalize' the treatment to a patient's individual needs. While the
      call for prospective randomized controlled trials to assess the effective use of
      such measurement may make sense in some cases, it is, when applied without
      distinction, hindering the implementation of personalized medicine. Important
      evidence for the validity and clinical effectiveness of using biomarkers, for
      example, a patient's genetic profile, can be gained from alternative approaches,
      including case-control and cohort studies, and retrospective analyses of data.
      Hence, we need to re-focus on approaches that are neither new nor unproven, but
      have been ignored over the last few decades.

PMID- 19604081
TI  - Relevance of CYP2D6 -1584C>G polymorphism for thioridazine:mesoridazine plasma
      concentration ratio in psychiatric patients.
AB  - AIMS: The CYP2D6 -1584C>G (rs1080985) polymorphism has been identified as another
      major factor for CYP2D6 function that is possibly associated with ultrarapid
      metabolism. The mutant -1584G promoter genotype seems to be consistently related
      to a higher protein expression than -1584C. However, the impact this SNP in the
      CYP2D6 promoter region has on plasma levels of patients taking CYP2D6 substrates,
      such as thioridazine, has not been studied. Previously, we showed the validity of
      the mesoridazine:thioridazine ratio to assess CYP2D6 activity in clinical
      settings. Therefore, the aim of this study was to analyze the relationship
      between the presence of the CYP2D6 -1584C>G polymorphism and the plasma
      concentrations of thioridazine and its metabolites in a previously studied
      population of patients in order to evaluate the implications for CYP2D6
      hydroxylation capacity. MATERIALS & METHODS: The CYP2D6 -1584C>G polymorphism was
      determined by using a PCR-RFLP method in 61 Caucasian psychiatric patients
      receiving thioridazine monotherapy. RESULTS: Among patients with two active
      CYP2D6 genes, there were significant differences in the thioridazine:mesoridazine
      plasma concentrations ratio (p < 0.05) among the three CYP2D6 -1584C>G genotype
      groups. Moreover, in this group of patients the thioridazine:mesoridazine ratio
      was lower (p < 0.05) in carriers of CYP2D6 -1584G allele than in patients
      homozygous for CYP2D6 -1584C allele. However, no differences in thioridazine or
      its metabolite concentrations between homozygous CYP2D6 -1584C allele carriers
      and carriers of the -1584G allele were found. CONCLUSION: According to the
      present results the concentration ratio of thioridazine to mesoridazine was
      related to the CYP2D6 -1584C>G polymorphism. It is likely that individuals who
      carry CYP2D6 -1584G versus homozygotes for the -1584C allele may present an
      increased CYP2D6 activity.

PMID- 19604082
TI  - Thiopurine methyltransferase and thiopurine metabolite testing in patients with
      inflammatory bowel disease who are taking thiopurine drugs.
AB  - Thiopurine methyltransferase genotyping and thiopurine metabolite testing has
      been established as an adjunct to monitoring patients taking thiopurine drugs.
      This special report describes the clinical implications for this type of testing
      for patients with inflammatory bowel disease who are taking thiopurine drugs. A
      total of 10% of patients were found to be intermediate metabolizers and the mean
      dosage (in mg/kg equivalent) was lower in intermediate metabolizers than
      extensive metabolizers. The metabolite levels did not correlate with scores
      measuring clinical severity but levels of 6-methylmercaptopurine were related to
      the dosage of the drugs. Despite considerable study of thiopurine
      methyltransferase testing in the literature, it is still not widely used in many
      geographical areas. This study adds to the evidence about using such testing as
      well as expanding the role of simultaneously measuring thiopurine metabolites.
      Further work is planned to evaluate the uptake when such testing becomes
      available locally as a clinical service.

PMID- 19604083
TI  - The G allele of SNP E1/A118G at the mu-opioid receptor gene locus shows genomic
      evidence of recent positive selection.
AB  - Opioid drug response and pain perception differs greatly amongst different
      individuals. The micro-opioid receptor (MOR) is the main receptor target for
      important opioid analgesics. As SNPs may contribute to interindividual
      differences in drug response, in silico signatures of recent positive selection
      (RPS) were utilized to seek out potentially functional SNPs in the MOR gene in
      order to facilitate the prioritization of SNPs for evaluation in genetic
      association studies. Out of over 1000 SNPs at the MOR locus, 184 high-frequency
      SNPs were interrogated for signatures of RPS. A total of five SNPs (four
      noncoding and one nonsynonymous coding) demonstrated in silico evidence of RPS.
      Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to
      be functionally important, showed in silico evidence of RPS. This reaffirms the
      feasibility of utilizing in silico signatures of RPS to identify potentially
      functionally significant SNPs for association studies. Interestingly, the
      positively selected G allele of this RPS SNP was also predicted to create a novel
      exon splice enhancer as well as p53 binding sites.

PMID- 19604084
TI  - Relation between CYP2D6 genotype, personality, neurocognition and overall
      psychopathology in healthy volunteers.
AB  - AIMS: A lower serotonin/higher dopamine tone in CYP2D6 poor metabolizers (PMs)
      versus extensive metabolizers (EMs) has been postulated, which is consistent with
      our prior research showing behavioral traits related to anxiety and impulsivity
      in PMs. This tone could also be related to PMs vulnerability to cognitive
      functioning and/or psychopathology. Therefore, the present study aimed to analyze
      the relationship between CYP2D6 genotype and personality, cognition and
      psychopathological vulnerability. The influence of affective state in these
      relationships was also analyzed. MATERIALS & METHODS: A total of 144 healthy
      volunteers from the University of Extremadura (Spain) were evaluated by CYP2D6
      genotypes, overall psychopathology (Symptom Checklist-90-revised [SCL-90-R]),
      personality (Karolinska Scales of Personality [KSP] and Temperament and Character
      Inventory [TCI-R]) and on cognitive functions with computerized CANTAB tests.
      RESULTS: PMs (n = 11) versus EMs (n = 133) (Mann-Whitney U-tests) presented
      higher 'impulsivity' in both KSP and TCI-R, and better performance of sustained
      attention (on the Rapid Visual Information Processing test) and lower overall
      psychopathology with all PMs scoring below 0.7 on SCL-90-R ('positive affect'
      group). There were differences between all participants scoring below (n = 107)
      and above (n = 37) 0.7 on SCL-90-R in most personality measures. Comparisons
      between PMs (n = 11) and EMs (n = 96) with SCL-90-R less than 0.7 maintained
      those results for KSP and CANTAB but also yielded greater scores on the TCI-R
      'perfectionism' subscale in PMs. In multivariate analyses controlled for age, sex
      and psychopathology, KSP-impulsiveness, CANTAB-sustained attention, spatial
      working memory and paired associate learning were significantly different in PMs
      versus EMs. CONCLUSION: In the studied population of healthy volunteers, PMs
      versus EMs showed lower vulnerability to psychopathology and greater impulsivity.
      Moreover, differences in neurocognition were found. The cross-study
      reproducibility of the relationship between CYP2D6 and personality may be
      difficult due to the influence of psychopathology among other factors. The
      personality and cognitive factors found in PMs appear compatible with a low
      serotonin/high dopamine balance.

PMID- 19604085
TI  - Promise of pharmacogenomics in smoking cessation.

PMID- 19604088
TI  - Conference scene: initiatives on future biobanking in pharmacogenomics.
AB  - The conference 'Biobanking in Pharmacogenetics' was held on the 23rd and 24th of
      April 2009 in London, UK. The conference was organized by the European Federation
      for Pharmaceutical Sciences European Research Network on
      Pharmacogenetics/Pharmacogenomics. The European Association for Clinical
      Pharmacology and Therapeutics, GlaxoSmithKline and the Dutch Top Institute Pharma
      provided financial sponsorship.

PMID- 19604089
TI  - Pharmacodynamic genes do not influence risk of neutropenia in cancer patients
      treated with moderately high-dose irinotecan.
AB  - AIMS: A recent study found that variation in camptothecin pharmacodynamic genes
      (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in
      irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that
      these genes might predict outcomes to irinotecan-based therapies. The present
      study was conducted to evaluate previous gene associations using an independent
      sample of patients receiving irinotecan. MATERIALS & METHODS: DNA was isolated
      from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and
      genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1.
      Associations between genotypes and haplotypes and log(absolute neutrophil count
      nadirs) were assessed by linear regression. RESULTS: No associations were
      observed. CONCLUSION: Our findings suggest that the genes we tested do not
      influence toxicity of irinotecan when adminstered at 300-350 mg/m2.

PMID- 19604090
TI  - Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes in
      metastatic gastric cancer.
AB  - AIMS: S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5
      fluorouracil mainly by CYP2A6. We evaluated the association between CYP2A6
      polymorphisms and treatment outcome in metastatic gastric cancer patients treated
      with S-1 plus docetaxel. MATERIALS & METHODS: Chemonaive patients received S-1 40
      mg/m(2) twice daily on days 1-14 and docetaxel 35 mg/m(2) on days 1 and 8 of a 3
      week cycle. We analyzed the wild-type (W) allele (CYP2A6*1) and four variant (V)
      alleles that abolish or reduce enzyme activity (CYP2A6*4, *7, *9 and *10). A
      total of 50 patients were enrolled. RESULTS: The genotype frequencies were as
      follows: W/W (n=14, 28%), W/V (n=26, 52%) and V/V (n=0, 20%). Patients having
      fewer variant alleles had significantly better response rates (W/W vs W/V vs
      V/V=79 vs 65 vs 30%; p=0.04) and median progression-free survival (W/W vs W/V vs
      V/V=8.1 vs 6.9 vs 3.1 months; p=0.0009). CONCLUSION: Our findings showed that the
      CYP2A6 genotype correlated with the treatment efficacy of S-1-based chemotherapy
      in previously untreated metastatic gastric cancer patients.

PMID- 19604091
TI  - Utilization of pharmacogenomics and therapeutic drug monitoring for opioid pain
      management.
AB  - AIMS: The use of medication in pain management currently involves empirical
      adjustment based on observed clinical outcome and the presence of adverse drug
      reactions. In this study, pharmacogenomics and therapeutic drug monitoring were
      used to evaluate the clinical effectiveness of genotyping chronic pain patients
      on analgesic therapy. It was hypothesized that patients who have inherited
      polymorphisms in CYP2D6 that make them poor or intermediate metabolizers of
      opioid medications would have higher steady-state concentrations of those opioids
      and may be more likely to experience adverse drug reactions. MATERIALS & METHODS:
      In an attempt to investigate the relationship between the polymorphic enzymes,
      steady-state drug concentrations, therapeutic effects and side effects, 61
      patients were clinically evaluated and genotyped, and drug concentrations were
      measured and outcomes analyzed. Samples were collected and DNA extracted from
      whole blood using a Puregene DNA isolation kit. CYP2D6 genotyping (*3, *4, *5,
      *6, *7, *8 and gene duplication) were carried out using Pyrosequencing. Steady
      state plasma concentrations of methadone, oxycodone, hydrocodone and tramadol
      were determined by HPLC tandem mass spectrometry. RESULTS: The results
      demonstrated the prevalence of CYP2D6 polymorphisms in the population undergoing
      pain management was not statistically different from the general population. The
      majority of the pain patients (54%) were extensive metabolizers; 41% were
      intermediate metabolizers and 5% poor metabolizers. Poor metabolizers in general
      tended to have the highest steady-state drug concentrations compared with
      extensive metabolizers (poor metabolizers > intermediate metabolizers > extensive
      metabolizers) although this wasn't statistically significant. Also, a
      relationship between oxycodone steady-state drug concentrations and pain relief
      was found. A total of 80% of patients reporting adverse drug reactions also had
      impaired CYP2D6 metabolism. The remaining 20% with adverse drug reactions had
      other cofactors (i.e., drug-drug interactions) that could explain the toxicity.
      CONCLUSION: These results suggest that patient care may be improved by genotyping
      and following therapeutic drug concentrations. Benefits include increased
      efficiency in proper drug selection, dose optimization and minimization of
      adverse drug reactions to improve patient outcome and safety. In addition, this
      study clearly demonstrated a relationship between oxycodone steady-state drug
      concentrations and pain relief. Future large-scale prospective studies are needed
      to confirm the clinical value of using genetic information to guide pain
      management therapy.

PMID- 19604092
TI  - Association of the alpha 2A adrenergic receptor -1291C/G polymorphism and
      antipsychotic-induced weight gain in European-Americans.
AB  - AIMS: To investigate the -1291 C/G promoter polymorphism (rs1800544) of the
      adrenergic alpha-2A receptor (ADRA2A) with clozapine-/olanzapine-induced weight
      gain in European-Americans and African-Americans. The alpha-adrenergic receptors
      inhibit lipolysis in the adipose tissue and are involved in weight gain
      regulation. Moreover, two previous studies indicated an association with
      antipsychotic-induced weight gain with the same polymorphism in Asian
      populations. MATERIALS & METHODS: We analyzed a relatively large (n=129) and well
      characterized group of patients and monitored them for a period of 6-14 weeks.
      Our refined sample consisted of 60 European-Americans and 39 African-Americans on
      clozapine or olanzapine, prospectively. RESULTS: In European-Americans, we
      observed a significant difference in weight gain across the genotypic categories
      (p=0.046). The carriers of the C allele gained more weight compared with the
      subjects homozygous for the GG allele (CC + CG vs GG; 3.73 +/- 4.13 kg vs 0.23 +/
      2.92 kg; p=0.013). We did not find a significant association in African
      Americans, although the sample size was probably too small. CONCLUSION: Our
      observations suggest a possible role of ADRA2A polymorphisms in clozapine
      /olanzpaine-induced weight gain in subjects of European descent.

PMID- 19604094
TI  - Rapid and cost-effective SNP detection method: application of SmartAmp2 to
      pharmacogenomics research.
AB  - Pharmacogenomics data can facilitate our understanding of the sources of
      variability in drug response, which can potentially lead to improved safety and
      efficacy of drug therapy for individual patients. A key requirement for the
      development of individualized medicine or personalized therapy is the ability to
      rapidly and conveniently test patients for genetic polymorphisms and/or
      mutations. However, in today's world, genotyping technology remains a bottleneck
      in clinical applications because of its slow speed and high cost. Therefore, we
      have recently developed a rapid and cost-effective method for SNP detection,
      named Smart Amplification Process 2 (SmartAmp2), which enables us to detect
      genetic polymorphisms or mutations in 30-45 min under isothermal conditions
      without DNA isolation and PCR amplification. This article presents the SNP
      detection method and its underlying molecular mechanism as well as clinical
      research applications.

PMID- 19604093
TI  - Genetic polymorphisms, their allele combinations and IFN-beta treatment response
      in Irish multiple sclerosis patients.
AB  - INTRODUCTION: IFN-beta is widely used as first-line immunomodulatory treatment
      for multiple sclerosis. Response to treatment is variable (30-50% of patients are
      nonresponders) and requires a long treatment duration for accurate assessment to
      be possible. Information about genetic variations that predict responsiveness
      would allow appropriate treatment selection early after diagnosis, improve
      patient care, with time saving consequences and more efficient use of resources.
      MATERIALS & METHODS: We analyzed 61 SNPs in 34 candidate genes as possible
      determinants of IFN-beta response in Irish multiple sclerosis patients.
      Particular emphasis was placed on the exploration of combinations of allelic
      variants associated with response to therapy by means of a Markov chain Monte
      Carlo-based approach (APSampler). RESULTS: The most significant allelic
      combinations, which differed in frequency between responders and nonresponders,
      included JAK2-IL10RB-GBP1-PIAS1 (permutation p-value was p(perm) = 0.0008),
      followed by JAK2-IL10-CASP3 (p(perm) = 0.001). DISCUSSION: The genetic mechanism
      of response to IFN-beta is complex and as yet poorly understood. Data mining
      algorithms may help in uncovering hidden allele combinations involved in drug
      response versus nonresponse.

PMID- 19604097
TI  - Reorganization and preservation of motor control of the brain in spinal cord
      injury: a systematic review.
AB  - Reorganization of brain function in people with CNS damage has been identified as
      one of the fundamental mechanisms involved in the recovery of sensorimotor
      function. Spinal cord injury (SCI) brain mapping studies during motor tasks aim
      for assessing the reorganization and preservation of brain networks involved in
      motor control. Revealing the activation of cortical and subcortical brain areas
      in people with SCI can indicate principal patterns of brain reorganization when
      the neurotrauma is distal to the brain. This review assessed brain activation
      after SCI in terms of intensity, volume, and somatotopic localization, as well as
      preservation of activation during attempted and/or imagined movements. Twenty
      five studies meeting the inclusion criteria could be identified in Medline (1980
      to January 2008). Relevant characteristics of studies (level of lesion, time
      after injury, motor task) and mapping techniques varied widely. Changes in brain
      activation were found in both cortical and subcortical areas of individuals with
      SCI. In addition, several studies described a shift in the region of brain
      activation. These patterns appeared to be dynamic and influenced by the level,
      completeness, and time after injury, as well as extent of clinical recovery. In
      addition, several aspects of reorganization of brain function following SCI
      resembled those reported in stroke. This review demonstrates that brain networks
      involved in different demands of motor control remain responsive even in chronic
      paralysis. These findings imply that therapeutic strategies aimed at restoring
      spinal cord function, even in people with chronic SCI, can build on preserved
      competent brain control.

PMID- 19604098
TI  - Recovery of afferent function and synaptic strength in hippocampal CA1 following
      traumatic brain injury.
AB  - Cortical contusion injury can result in the partial loss of ipsilateral CA3
      neurons within 48 h, leading to a proportional reduction in the number of
      afferent fibers to CA1 stratum radiatum. While the loss of afferent input to CA1
      exhibits a remarkable, albeit incomplete, recovery over the next few weeks,
      little is known about the functional status of presynaptic afferents during the
      depletion and recovery phases following injury. Here, we prepared hippocampal
      slices from adult Sprague Dawley rats at 2, 7, and 14 days after lateral cortical
      contusion injury and measured fiber volley (FV) amplitudes extracellularly in CA1
      stratum radiatum. Field excitatory post-synaptic potentials (EPSPs) were also
      measured and plotted as a function of FV amplitude to assess relative synaptic
      strength of residual and/or regenerated synaptic contacts. At 2 days post-injury,
      FV amplitude and synaptic strength were markedly reduced in the ipsilateral,
      relative to the contralateral, hippocampus. FV amplitude in ipsilateral CA1
      showed a complete recovery by 7 days, indicative of a post-injury sprouting
      response. Synaptic strength in ipsilateral CA1 also showed a dramatic recovery
      over this time; however, EPSP-to-FV curves remained slightly suppressed at both
      the 7 and 14 day time points. Despite these deficits, ipsilateral slices retained
      the capacity to express long-term potentiation, indicating that at least some
      mechanisms for synaptic plasticity remain intact, or are compensated for. These
      results are in agreement with anatomical evidence showing a profound
      deafferentation, followed by a remarkable re-enervation, of ipsilateral CA1 in
      the first few weeks after traumatic brain injury. Although plasticity mechanisms
      appear to remain intact, synaptic strength deficits in CA1 could limit
      information throughput in the hippocampus, leading to persistent memory
      dysfunction.

PMID- 19604099
TI  - Difficulty of elderly SCI subjects to translate motor recovery--"body function"-
      into daily living activities.
AB  - The objective of this retrospective analysis was to determine whether outcome of
      body functions and activities as well as length of stay of inpatient
      rehabilitation is related to age in patients with traumatic spinal cord injury
      (SCI). Data were collected from a European network of 17 SCI rehabilitation
      centers (EM-SCI); a total of 237 traumatic SCI subjects were included.
      Assessments were performed at 1, 6, and 12 months after SCI. The measures
      analyzed were motor score according to the American Spinal Injury Association,
      Spinal Cord Independence Measure (SCIM), gait speed, and length of stay.
      Correlation analysis was applied to quantify the association between age and
      change in the outcome measures. A positive relationship was found between age and
      neurological recovery in both the first and second 6-month periods of assessment.
      A negative relationship was found between age and change in SCIM in the second 6
      month period after SCI. A negative relationship between age and gait speed was
      observed in the first half year. Length of stay was not associated with age. It
      was concluded that age is an important determining factor for functional outcome
      after SCI and that elderly patients have difficulties in translating an
      improvement in neurological outcome into functional changes. Therefore,
      rehabilitation approaches in elderly subjects should focus on functional
      training.

PMID- 19604096
TI  - Key role of sulfonylurea receptor 1 in progressive secondary hemorrhage after
      brain contusion.
AB  - An important but poorly understood feature of traumatic brain injury (TBI) is the
      clinically serious problem of spatiotemporal progression ("blossoming") of a
      hemorrhagic contusion, a phenomenon we term progressive secondary hemorrhage
      (PSH). Molecular mechanisms of PSH are unknown and efforts to reduce it by
      promoting coagulation have met with equivocal results. We hypothesized that PSH
      might be due to upregulation and activation of sulfonylurea receptor 1 (SUR1)
      regulated NC(Ca-ATP) channels in capillary endothelial cells, predisposing to
      oncotic death of endothelial cells and catastrophic failure of capillary
      integrity. Anesthetized adult male rats underwent left parietal craniectomy for
      induction of a focal cortical contusion. The regulatory subunit of the channel,
      SUR1, was prominently upregulated in capillaries of penumbral tissues surrounding
      the contusion. In untreated rats, PSH was characterized by progressive
      enlargement of the contusion deep into the site of cortical impact, including
      corpus callosum, hippocampus, and thalamus, by progressive accumulation of
      extravasated blood, with a doubling of the volume during the first 12 h after
      injury, and by capillary fragmentation in penumbral tissues. Block of SUR1 using
      low-dose (non-hypoglycemogenic) glibenclamide largely eliminated PSH and
      capillary fragmentation, and was associated with a significant reduction in the
      size of the necrotic lesion and in preservation of neurobehavioral function.
      Antisense oligodeoxynucleotide against SUR1, administered after injury, reduced
      both SUR1 expression and PSH, consistent with a requirement for transcriptional
      upregulation of SUR1. Our findings provide novel insights into molecular
      mechanisms responsible for PSH associated with hemorrhagic contusions, and point
      to SUR1 as a potential therapeutic target in TBI.

PMID- 19604100
TI  - Abnormal corticospinal excitability in traumatic diffuse axonal brain injury.
AB  - This study aimed to investigate the cortical motor excitability characteristics
      in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A
      variety of excitatory and inhibitory transcranial magnetic stimulation (TMS)
      paradigms were applied to primary motor cortices of 17 patients and 11 healthy
      controls. The parameters of testing included resting motor threshold (MT), motor
      evoked potential (MEP) area under the curve, input-output curves, MEP
      variability, and silent period (SP) duration. The patient group overall revealed
      a higher MT, smaller MEP areas, and narrower recruitment curves compared to
      normal controls (p < 0.05). The alterations in excitability were more pronounced
      with an increase in DAI severity (p < 0.005) and the presence of motor impairment
      (p < 0.05), while co-existence of focal lesions did not affect the degree of MEP
      changes. MEP variability was significantly lower in the group with motor
      impairment only (p < 0.05). The intracortical inhibition, as revealed by SP
      duration, did not exhibit any significant differences in any of the patient
      groups. In conclusion, our findings expand the concept that impairment of the
      excitatory and inhibitory phenomena in the motor cortex does not proceed in
      parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore,
      these data suggest that alterations in the corticospinal excitatory mechanisms
      are determined predominantly by the severity of DAI, and show a significant
      relationship with clinical motor dysfunction following severe trauma diffusely
      affecting the motor cortical connections. In severe TBI, motor and functional
      recovery might be linked to restitution of normal corticospinal mechanisms,
      indexed by normalization of the cortical excitability parameters.

PMID- 19604101
TI  - Progressive brain changes on serial manganese-enhanced MRI following traumatic
      brain injury in the rat.
AB  - Traumatic brain injury (TBI) has a high incidence of long-term morbidity.
      Manganese-enhanced MRI (MEMRI) provides high contrast structural and functional
      detail of the brain in-vivo. The study utilized serial MEMRI scanning in the
      fluid percussion injury (FPI) rat's model to assess long-term changes in the
      brain following TBI. Rats underwent a left-sided craniotomy and a 3.5 atmosphere
      FPI pulse (n = 23) or sham procedure (n = 22). MEMRI acquisition was performed at
      baseline, 1 day, 1 month, and 6 months after FPI. Volume changes and MnCl(2)
      enhancement were measured blindly using region-of-interest analysis and the
      results analyzed with repeated measures MANOVA. Compared to the shams, FPI
      animals showed a progressive decrease in brain volume from 1 (right, p = 0.02;
      left, p = 0.008) to 6 months (right, p = 0.04; left, p = 0.006), with progression
      over time (F = 7.16, p = 0.00018). Similar changes were found in the cortex and
      the hippocampus. Conversely, the ventricular volume was increased at 1 (p = 0.02)
      and 6 months (p = 0.003), with progression over time (F = 7.27, p = 0.0001).
      There were no differences in thalamic or amygdalae volumes. The severity of the
      early neuromotor deficits and the T2 signal intensity of the subacute focal
      lesion were highly predictive of the severity of the long-term hippocampal
      decrease, and the former was also associated with the degree of neuronal
      sprouting. Differential MnCl(2) enhancement occurred only in the dentate gyrus at
      1 month on the side of trauma (p = 0.04). Progressive functional and structural
      changes occur in specific brain regions post-FPI. The severity of the neuromotor
      deficit and focal signal changes on MRI subacutely post-injury are predictive of
      severity of these long-term neurodegenerative changes.

PMID- 19604104
TI  - An interview with Michael M. Gottesman, M.D. Interview by Vicki Glaser.
AB  - Dr. Michael Gottesman obtained his M.D. from Harvard University Medical School,
      completed his internship and residency in medicine at the Peter Bent Brigham
      Hospital in Boston, and received his postdoctoral research training in molecular
      genetics with Martin Gellert at the National Institutes of Health (NIH). After a
      year as an assistant professor in the Department of Anatomy at Harvard, he moved
      to the NIH in 1976. He currently serves as the NIH Deputy Director for Intramural
      Research as well as Chief of the Laboratory of Cell Biology.

PMID- 19604102
TI  - Angiotensin II type 1 receptor blocker telmisartan reduces cerebral infarct
      volume and peri-infarct cytosolic phospholipase A(2) level in experimental
      stroke.
AB  - The angiotensin II type 1 receptor (AT(1)R) blocker (ARB) telmisartan is a unique
      drug that has a neuroprotective action and acts as an agonistic ligand for
      peroxisome proliferator-activated receptor-gamma. We produced rat models of
      middle cerebral artery occlusion and examined infarct volume as well as
      immunohistochemical localization and protein expression levels of cytosolic
      phospholipase A(2) (cPLA(2)), which is involved in neurotoxicity, in brains
      obtained 24 h after occlusion. Rats pretreated for 7 days with various doses of
      telmisartan or vehicle (n = 8) were compared. The infarct volume was
      significantly reduced in the 1.0 mg/kg dosage group compared with that of other
      dosage groups and vehicle group. Furthermore, pretreatment with telmisartan 1.0
      mg/kg induced significant amelioration of sensorimotor function in forelimb and
      hindlimb placing tests. Histopathologically, neurons in the peri-infarct cortical
      regions of vehicle-pretreated rats showed acute ischemic changes, but neurons in
      telmisartan-pretreated rats appeared normal. Immunohistochemically, cPLA(2)
      reactivity was localized in ischemic neurons but not in intact neurons. On
      immunoblots, protein expression levels of total and active cPLA(2) in peri
      infarct cortex were significantly reduced in telmisartan-treated rats compared
      with vehicle-treated rats. The present results provide in vivo evidence that
      telmisartan reduces cerebral infarct volume and cPLA(2) protein expression in
      peri-infarct cortex, suggesting an association between neuroprotection and
      inhibition of cPLA(2) signaling in cerebral ischemia.

PMID- 19604106
TI  - Development of multiplexed microarray binding assays for high-throughput drug
      discovery.
AB  - The ability to combine primary hit identification assays with target profiling
      would significantly streamline the current drug discovery process. Working
      towards this end, we report here the development of a microarray-based ligand
      binding assay that supports multiplexed analysis of G protein-coupled receptor
      systems in a 96-well microplate format that is compatible with the equipment and
      infrastructure typical of high-throughput screening laboratories. A prototype
      microarray was generated by pin-printing seven different receptors within the
      wells of a specially coated glass-bottom microplate and assaying with a cocktail
      of fluorescent ligands. Development of the multiplexed system included
      optimization of methods for depositing receptor membrane proteins and
      establishing a generic set of assay conditions that simultaneously satisfied the
      pharmacology requirements of all of the receptor systems included on the array.
      The multiplexed system is shown to produce valid pharmacological results as
      evidenced by its ability to report K(i) values for receptor-specific fluorescent
      ligands and rank ordered potencies for diagnostic displacing compounds comparable
      to values generated by conventional simplexed assays. Moreover, the results of a
      40-compound mini-screen confirmed that the assay accurately identifies valid
      hits. The results suggest the assay may be immediately suitable for routine
      profiling tasks and demonstrate the potential of the format for high-throughput
      multiplexed drug discovery.

PMID- 19604107
TI  - All in one with chAMPion: a generic luminescence assay platform for any GPCR
      signaling type.

PMID- 19604110
TI  - Analysis of PTEN gene mutations in a Turkish patient with Cowden syndrome.
AB  - Cowden syndrome (CS), an autosomal dominant disorder, is associated with germline
      mutations of the PTEN (phosphatase, tensin homolog, deleted on chromosome TEN)
      gene. PTEN mutations were linked to several human neoplasms. Clinical diagnosis
      has been based on Consortium criteria, but detection of mutations in the PTEN
      gene has importance in accurate diagnosis. This article presents a female patient
      with classic features of the syndrome and gives the result of first PTEN mutation
      analysis result in a Turkish CS patient. The patient, who suffered from
      trichilemmomas, papillomatous lesions, lipomas, thyroid lesions, gastrointestinal
      hamartomas, and fibrocystic disease of the breast, is consistent with the
      diagnostic criteria of CS. The exons and intron/exon boundaries of the PTEN gene
      were analyzed by polymerase chain reaction and direct sequencing. We analyzed the
      clinical features and DNA in a Turkish patient with CS. We found a single
      nucleotide substitution in the splicing acceptor site of intron 5 of the PTEN
      gene (IVS5-2A > C). It is not clear whether which types of PTEN mutations are
      responsible for particular phenotypes. This germline PTEN mutation, IVS5-2A -->
      C, has been reported once before, but the clinical features differ from our
      patient. Also, this is the first reported PTEN mutation from Turkey.

PMID- 19604111
TI  - Factor V Leiden and the risk of venous thrombosis, myocardial infarction, and
      stroke: a case-control study in Venezuela.
AB  - The most common genetic defect associated with deep vein thrombosis (DVT) is a
      mutation in the Factor V gene (G1691A), known as Factor V Leiden (FVL). We
      investigated the genotypes for FVL in 571 individuals in Venezuela: 208 patients
      with DVT, 175 patients with acute myocardial infarction, 54 patients with stroke,
      and 134 control subjects. Our results showed in the population analyzed here that
      the FVL was associated with a fourfold increase in the risk for DVT (odds ratio,
      4.24; 95% confidence interval, 1.35-14.79); particularly, women carriers showed a
      6.5-fold increase in the risk for DVT. No relation was observed between the
      presence of FVL and the risk for acute myocardial infarction or stroke. In
      conclusion, a clear association between the FVL mutation and DVT was observed in
      the population analyzed in Venezuela. These results are in agreement with those
      found in other populations with different ethnic backgrounds.

PMID- 19604112
TI  - Plasminogen activator inhibitor type-1 gene 4G/5G polymorphism in Turkish adult
      patients with asthma.
AB  - AIM: This study has been performed on asthmatic patients in the Turkish
      population to determine the frequency of 4G/5G polymorphism genotypes of
      plasminogen activator inhibitor type-1 gene, and with the aim of examining the
      role of this polymorphism in asthma development. METHODS: Genomic DNA obtained
      from 165 persons (98 patients with asthma and 67 healthy controls) was used in
      the study. DNA was multiplied with polymerase chain reaction using 4G and 5G
      allele-specific primers. Polymerase chain reaction products were assessed with
      CCD camera by being exposed to 2% agarose gel electrophoresis. Results were
      evaluated with chi-square test. RESULTS: No statistically significant difference
      between the groups with respect to genotype distribution was found (p > 0.05) in
      the study. The 4G allele frequency was indicated as 48% and 5G allele was as 52%
      in patients, whereas this was 50-50% in the control group. CONCLUSION: It has
      been established by this study that 4G/5G polymorphism genotypes of plasminogen
      activator inhibitor type-1 gene do not play a role in the development of asthma
      in the Turkish population.

PMID- 19604113
TI  - GPR143 mutational analysis in two Italian families with X-linked ocular albinism.
AB  - X-linked ocular albinism type 1 (OA1) is caused by mutations in G protein-coupled
      receptor 143 (GPR143) gene, which encodes a membrane glycoprotein localized to
      melanosomes. GPR143 mainly affects pigment production in the eye, resulting in
      optic changes associated with albinism, including hypopigmentation of the retina,
      nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers,
      and reduced visual acuity. We report the mutational analysis of the GPR143 gene
      on two unrelated families with OA1 using direct sequencing and real-time
      quantitative polymerase chain reaction. We identified the c.564_565delCT, a 2-bp
      deletion in family 1, and we mapped the breakpoints at nucleotide level of the
      novel intragenic deletion g.5360_6371del1012, encompassing exon 2, in family 2.
      Our results confirm that GPR143 is the major locus for OA1 and that exon 2 is a
      region of high susceptibility to deletions. Finally, we emphasize the
      quantitative polymerase chain reaction as a valid tool for diagnosis of deletions
      in the GPR143 gene.

PMID- 19604114
TI  - Natural variability of NS3 protease in patients infected with genotype 4
      hepatitis C virus (HCV): implications for antiviral treatment using specifically
      targeted antiviral therapy for HCV.
AB  - To analyze the genetic diversity of the NS3 gene in patients infected with
      hepatitis C virus (HCV) genotype 4 (HCV-4) and to assess the possible effects of
      the gene polymorphism (or variability) on drug susceptibility, 43 NS3 gene
      sequences were determined for 53 selected patients with HCV-4 infection. NS3
      sequencing, like NS5B sequencing, allowed correct subtype determination. Most
      residues that were located within the catalytic triad or the NS4-binding region
      or that were involved in metal binding were highly conserved and identical to
      those found in HCV genotype 1. Compared with HCV genotype 1, all HCV-4 NS3
      protein presented V36L and C16T residue changes that could potentially reduce
      antiprotease activity. The efficacy of antiprotease in HCV-4-infected patients
      remains to be proven in large clinical trials.

PMID- 19604116
TI  - Arcobacter butzleri induces barrier dysfunction in intestinal HT-29/B6 cells.
AB  - BACKGROUND: Arcobacter butzleri causes watery diarrhea and bacteremia. Although,
      recently, more cases of diarrhea have been caused by Arcobacter species, very
      little is known about its pathogenesis, the identification of which is the aim of
      this study. METHODS: Human HT-29/B6 colonic epithelial monolayers were apically
      inoculated with A. butzleri. Transepithelial resistance and macromolecule fluxes
      were measured in Ussing chambers. Tight junction protein expression was analyzed
      by Western blotting, and subcellular distribution was analyzed by confocal laser
      scanning microscopy. RESULTS: Infection of HT-29/B6 caused a decrease in
      transepithelial resistance to 30% and an increase in paracellular permeability to
      fluorescein (10.8+/-3.5 10(-6) cm/s vs. 1.8+/-0.6 10(-6) cm/s in control; P<.05)
      and dextran-4 kDa (0.036+/-0.005 10(-6) cm/s vs. 0.015+/-0.002 10(-6) cm/s in
      control; P<.01). This effect was time and dose dependent and was also caused by
      bacterial lysates showing heat and proteinase-K sensitivity. As structural
      correlate, expression of the tight junctional proteins claudin-1, -5, and -8 was
      reduced, and claudin-1 and -8 were redistributed off the tight junctional strands
      forming intracellular aggregates. Furthermore, A. butzleri induced epithelial
      apoptosis (3-fold). CONCLUSIONS: A. butzleri induces epithelial barrier
      dysfunction by changes in tight junction proteins and induction of epithelial
      apoptosis, which are mechanisms that are consistent with a leak flux type of
      diarrhea in A. butzleri infection.

PMID- 19604115
TI  - Peptides of a novel Mycobacterium tuberculosis-specific cell wall protein for
      immunodiagnosis of tuberculosis.
AB  - The sequencing of the Mycobacterium tuberculosis genome revealed the existence of
      several genes encoding novel proteins with unknown functions, one of which is the
      proline-threonine repetitive protein (PTRP; Rv0538). Genomic studies of various
      mycobacterial species and M. tuberculosis clinical isolates demonstrate that ptrp
      is specific to the M. tuberculosis complex and ubiquitous in clinical isolates.
      Enzyme-linked immunosorbent assay, Western blot analysis, and electron
      microscopic evaluation of M. tuberculosis subcellular fractions and intact
      bacteria confirm that PTRP is a cell wall protein. Antibodies to PTRP are present
      in serum specimens from human immunodeficiency virus (HIV)-negative, tuberculosis
      (TB)-positive and HIV-positive, TB-positive patients but not purified protein
      derivative (PPD)-negative or PPD-positive healthy control subjects, demonstrating
      its diagnostic potential. Epitope mapping of PTRP delineated 4 peptides that can
      identify >80% of sputum smear-positive and >50% of smear-negative, HIV-negative,
      TB-positive patients and >80% of HIV-positive, TB-positive patients. These
      results demonstrate that immunodominant epitopes of carefully selected M.
      tuberculosis-specific proteins can be used to devise a simple peptide-based
      serodiagnostic test for TB.

PMID- 19604117
TI  - CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic
      complex that suppresses Helicobacter pylori-induced cell-invasive phenotype.
AB  - BACKGROUND: Helicobacter pylori induces an invasive phenotype in gastric
      epithelial cells through a mechanism that requires the type IV secretion system
      and the phosphorylation of c-Met. The E-cadherin-catenin complex is a major
      component of the adherens junctions and functions as an invasion suppressor. We
      investigated whether E-cadherin has a role in H. pylori-induced, c-Met
      phosphorylation-dependent cell-invasive phenotype. METHODS: AGS cells that lack E
      cadherin and that are invasive to H. pylori stimulation were transduced with E
      cadherin and infected with H. pylori. NCI-N87 cells, which endogenously express E
      cadherin, were also used for infection experiments. RESULTS: E-cadherin was
      sufficient to suppress not only H. pylori-mediated cell-invasive phenotype but
      also c-Met and p120-catenin tyrosine phosphorylation. H. pylori infection led to
      increased interactions between E-cadherin and p120-catenin, c-Met and E-cadherin,
      and c-Met and p120-catenin. Using in vitro infection assays, we showed that H.
      pylori CagA interacts with E-cadherin, p120-catenin, and c-Met. Finally, using
      small interfering RNA, we showed that interactions between CagA and E-cadherin
      and between CagA and p120-catenin were established through c-Met. CONCLUSIONS: We
      suggest that H. pylori alters the E-cadherin-catenin complex, leading to
      formation of a multiproteic complex composed of CagA, c-Met, E-cadherin, and p120
      catenin. This complex abrogates c-Met and p120-catenin tyrosine phosphorylation
      and suppresses the cell-invasive phenotype induced by H. pylori.

PMID- 19604118
TI  - Cladribine: not just another purine analogue?
AB  - Cladribine was synthesized as a purine analogue drug that inhibited adenosine
      deaminase. It received FDA approval in the 1980s for treatment of hairy cell
      leukemia. Given its toxicity towards lymphocytes and its corresponding
      immunosuppressive effects, it has been studied and found efficacious in a variety
      of hematologic malignancies and autoimmune conditions, most recently multiple
      sclerosis. This review highlights pharmacological, toxicological and clinical
      data for the use of cladribine. It also discusses existing and new mechanisms
      that may contribute to its unique clinical activity. Emerging data show that in
      addition to its known purine nucleoside analogue activity, cladribine possesses
      epigenetic properties, inhibiting S-adenosylhomocysteine hydrolase and DNA
      methylation. This may contribute to its efficacy and highlights the importance of
      studying combination therapy with other epigenetic or targeted agents. Clinical
      trials are underway in a variety of malignant and nonmalignant conditions.

PMID- 19604119
TI  - Larotaxel: broadening the road with new taxanes.
AB  - Significant advances in cancer treatment have been achieved with novel targeted
      and state-of-the-art treatments. While the targeted treatments have received much
      attention in recent years, the more 'traditional' chemotherapeutic agents
      continue to play an important role in several malignancies. Former taxanes such
      as docetaxel and paclitaxel, with their broad anticancer activity, have
      contributed significantly to the improved treatment of a number of neoplastic
      diseases. Unfortunately, until now, the achievements obtained with these
      compounds have been mitigated by clinical limitations such as acquired or
      intrinsic resistance of tumors, poor CNS activity, allergic reactions and
      unfavorable toxicity profiles. Larotaxel (RPR 109881A) is a taxane analogue with
      a broad spectrum of activity and different toxicity profile and with the possible
      advantages of surpassing some mechanisms of resistance and penetrating into the
      CNS. The development path of this drug, its core clinical data and future
      treatment perspectives are discussed in this article.

PMID- 19604120
TI  - Novel antiarrhythmic drugs in atrial fibrillation: focus on tedisamil.
AB  - BACKGROUND: Even established and effective antiarrhythmic drugs (AADs) in atrial
      fibrillation (AF) are limited by their pro-arrhythmic and non-target organ side
      effects. Therefore the search continues for safer and effective new AADs.
      OBJECTIVE: This review will examine a novel AAD, tedisamil--a multichannel
      potassium channel blocker--and its antiarrhythmic properties, focusing on AF.
      METHODS: Review of the literature and studies assessing the effect of tedisamil
      in humans and animal models with atrial arrhythmia(s). CONCLUSION: Tedisamil
      appears to be effective for rhythm restoration in acute-onset AF patients. The
      proven anti-ischemic effect with tedisamil may be an added benefit. Further
      studies with tedisamil are needed to confirm its safety and long-term efficacy.

PMID- 19604121
TI  - Clinical overview on Lipoplatin: a successful liposomal formulation of cisplatin.
AB  - Nanoparticle formulations for packaging existing drugs have been used to treat
      cancer. Lipoplatin is a liposomal cisplatin encapsulated into liposome
      nanoparticles of an average diameter of 110 nm. Lipoplatin has substantially
      reduced the renal toxicity, peripheral neuropathy, ototoxicity, myelotoxicity as
      well as nausea/vomiting and asthenia of cisplatin in Phase I, II and III clinical
      studies with enhanced or similar efficacy to cisplatin. During clinical
      development, 10- to 200-fold higher accumulation of Lipoplatin in solid tumors
      compared to adjacent normal tissue was found in patients. Targeting of tumor
      vasculature by Lipoplatin in animals suggested its antiangiogenesis potential and
      Lipoplatin was proposed to act like a double-sword: as chemotherapy and an
      antiangiogenesis drug. Lipoplatin has finished successfully one Phase III non
      inferiority clinical study as first-line against NSCLC in its combination with
      paclitaxel showing statistically significant reduction in nephrotoxicity; two
      more Phase III studies are in progress, one in NSCLC with gemcitabine also
      showing noninferiority with reduced toxicity and another in squamous cell
      carcinoma of the head and neck with 5-fluorouracil. A registrational Phase II/III
      study against pancreatic cancer is in progress under the orphan drug status
      granted to Lipoplatin by the European Medicines Agency. Phase II studies are
      continuing in advanced breast cancer with vinorelbine and gastrointestinal
      cancers with radiotherapy and 5-fluorouracil. The highlights of the clinical
      development of Lipoplatin are reviewed.

PMID- 19604122
TI  - Cangrelor: a novel P2Y12 receptor antagonist.
AB  - Antiplatelet therapy is critical in the prevention of thrombotic complications of
      acute coronary syndrome and percutaneous coronary interventions. Current
      antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa antagonists)
      have demonstrated the capacity to reduce major adverse cardiac events. However,
      these agents have limitations that compromise their clinical utility. The
      platelet P2Y12 receptor plays a central role in platelet function and is a focus
      in the development of antiplatelet therapies. Cangrelor is a potent, competitive
      inhibitor of the P2Y12 receptor that is administered by intravenous infusion and
      rapidly achieves near complete inhibition of ADP-induced platelet aggregation.
      This investigational drug has been studied for use during coronary procedures and
      the management of patients experiencing acute coronary syndrome and is undergoing
      evaluation for use in the prevention of perioperative stent thrombosis.

PMID- 19604123
TI  - Avotermin for the improvement of scar appearance: a new pharmaceutical in a new
      therapeutic area.
AB  - Disfiguring scarring in the skin is an area of high medical need. Current
      treatments for scarring have variable or limited effectiveness and have typically
      not been evaluated in randomized, controlled, double-blind clinical trials. The
      prophylactic improvement in scar appearance, through administration of agents
      around the time of injury, represents a new therapeutic approach for which there
      are currently no registered pharmaceuticals. Extensive research into the
      mechanisms of scar-free and scar-forming healing has provided a robust scientific
      rationale for the development of avotermin (human recombinant TGF-beta3) as a
      potential therapeutic for the improvement of scar appearance in humans. The
      pioneering approach used for the clinical development of avotermin in this new
      indication has explained the efficacy and safety profile of avotermin in several,
      prospectively randomized, double-blind clinical studies in human volunteers and
      patients. These studies, which show a clear translation from preclinical efficacy
      models to the clinical environment, have shown that prophylactic scar improvement
      is pharmaceutically achievable. It is anticipated that therapeutics such as
      avotermin, with a sound mechanistic basis and proof of effectiveness in suitably
      robust clinical trials, will be available to meet the needs of patients in the
      foreseeable future.

PMID- 19604124
TI  - Matrix metalloproteinases in the pathophysiology and progression of gynecological
      malignancies: could their inhibition be an effective therapeutic approach?
AB  - BACKGROUND: MMPs are a group of zinc-dependent endopeptidases implicated in the
      degradation of extracellular matrix components. Angiogenesis, wound healing and
      tissue remodeling are the main processes in which MMPs have been implicated. MMPs
      also seem to play a role in the pathophysiological processes during tumorigenesis
      and are thought to have predictive value for clinical outcome. Alterations in the
      regulation of MMP expression are considered to be of significant importance in
      the development and progression of gynecological malignancies.
      OBJECTIVES/METHODS: This study provides a literature review on the involvement of
      MMPs in the development and progression of gynecological malignancies, their
      clinical significance and the potential use of natural and/or synthetic MMP
      Inhibitors (MMPIs) as a more targeted therapeutic approach to these neoplasms.
      RESULTS/CONCLUSIONS: There is mounting evidence that MMPs play an important role
      in development and progression of gynecological malignancies. Current results
      provide the basis for further investigation of their role in malignancies, the
      therapeutic potential of their inhibition and the side-effects that can be
      expected from the modulation of matrix remodeling during therapeutic
      intervention. Focused research on the combination of MMPIs with cytotoxic and/or
      antiangiogenic compounds might provide the key to more successful therapeutic
      approaches towards gynecological and other malignancies.

PMID- 19604125
TI  - Interleukin-1 beta targeted therapy for type 2 diabetes.
AB  - Since having been cloned in 1984, IL-1beta has been the subject of over 22,000
      citations in Pubmed, among them over 800 reviews. This is because of its numerous
      effects. IL-1beta is a regulator of the body's inflammatory response and is
      produced after infection, injury, and antigenic challenge. It plays a role in
      various diseases, including autoimmune diseases such as rheumatoid arthritis,
      inflammatory bowel diseases and type 1 diabetes, as well as in diseases
      associated with metabolic syndrome such as atherosclerosis, chronic heart failure
      and type 2 diabetes. Macrophage are the primary source of IL-1, but epidermal,
      epithelial, lymphoid and vascular tissues also synthesize IL-1. IL-1beta
      production and secretion have also been reported from pancreatic islets. Insulin
      producing beta-cells within pancreatic islets are specifically prone to IL-beta
      induced destruction and loss of function. Macrophage-derived IL-1beta production
      in insulin-sensitive organs, leads to progression of inflammation and induction
      of insulin resistance in obesity. We summarize the mechanisms involved in
      inflammation and specifically the IL-1beta signals that lead to the progression
      of insulin resistance and diabetes. We highlight recent clinical studies and
      experiments in animals and isolated islets using IL-1beta as a potential target
      for the therapy of type 2 diabetes.

PMID- 19604126
TI  - Predictive value of the respiratory syncytial virus risk-scoring tool in the term
      infant in Canada.
AB  - BACKGROUND: Palivizumab prophylaxis against respiratory syncytial virus (RSV)
      infection has been widely adopted for high-risk infants during the RSV season,
      based on country-specific guidelines. OBJECTIVE: To determine if a validated,
      risk-scoring tool (RST), can be applied to term, RSV-positive infants seen in the
      emergency room (ER) to predict need for hospitalization, in order to target
      prophylaxis cost effectively at a selected group of children. DESIGN:
      Retrospective, descriptive study. SETTING: McMaster Children's Hospital in
      Hamilton, Ontario, Canada. PARTICIPANTS: A total of 72, consecutive, term, RSV
      positive cases were identified retrospectively, from November through April
      during the 2006-2007 RSV season. METHODS: A questionnaire/chart review was
      conducted on 68 of 72 cases, to determine risk categories based on the RST. Four,
      trained abstractors, extracted pertinent data from the medical records of RSV
      positive patients. Means, standard deviations (SD), and percents were used to
      describe the study variables for hospitalized and ER patients discharged home.
      Chi-square tests were used to compare infants' risk factors to hospitalization.
      ANOVA was used for comparisons within and between risk groups and RST scores. A p
      value of <0.05 was considered statistically significant. RESULTS: The majority of
      infants scored in the low-risk category (n = 44), versus moderate (n = 16) or
      high risk (n = 8). Within the low-risk category, 27 (61%) of children were
      admitted to hospital compared to 17 (39%) who were treated in the ER and
      discharged home. The mean RST scores for those admitted to the pediatric
      intensive care unit/ward, the ward only, or those discharged home from the ER
      were 48.3 (n = 10), 41.0 (n = 36), and 36.5 (n = 22), respectively (p = 0.17).
      The mean number of risk factors for those discharged home versus hospitalized
      patients was 2.5 (1.3) and 2.97 (1.13), respectively (p = 0.15). Only two of
      eight cases in the high-risk group required intensive care. CONCLUSIONS: Overall,
      the risk-scoring tool did not discriminate between low versus moderate- to high
      risk RSV-positive term infants who require hospitalization which has cost
      implications, since universal prophylaxis of this cohort would be financially
      prohibitive. A larger study is necessary to establish risk factors that more
      accurately determine RSV hospitalization among term infants.

PMID- 19604127
TI  - Combinatorial hexapeptide ligand libraries (ProteoMiner): an innovative
      fractionation tool for differential quantitative clinical proteomics.
AB  - Blood serum samples are the major source for clinical proteomics approaches,
      which aim to identify diagnostically relevant or treatment-response related
      proteins. But, the presence of very high-abundance proteins and the enormous
      dynamic range of protein distribution hinders whole serum analysis. An innovative
      tool to overcome these limitations, utilizes combinatorial hexapeptide ligand
      libraries (ProteoMiner). Here, we demonstrate that ProteoMiner can be used for
      comparative and quantitative analysis of complex proteomes. We spiked serum
      samples with increasing amounts (3 microg to 300 microg) of whole E. coli lysate,
      processed it with ProteoMiner and performed quantitative analyses of 2D-gels. We
      found, that the concentration of the spiked bacteria proteome, reflected by the
      maintained proportional spot intensities, was not altered by ProteoMiner
      treatment. Therefore, we conclude that the ProteoMiner technology can be used for
      quantitative analysis of low abundant proteins in complex biological samples.

PMID- 19604128
TI  - Anion recognition properties of 2,2'-bipyridine derivative receptors containing
      phenol group.
AB  - A series of artificial 2,2'-bipyridine receptors (1, 2, 3) containing phenol
      group have been designed and synthesized. Their anion-binding properties are
      evaluated for various anions (F(-), Cl(-), Br(-), I(-), AcO(-) and H(2)PO(4)(-))
      by UV-vis titration experiment in order to research the impact of different
      substituents on anion-recognition properties. Results indicate that the anion
      binding abilities can be tuned by electron push-pull properties of substituents
      on the phenyl ortho- or para-position of the receptors. In addition, receptor 1
      is sensitive for F(-) detection without the interference of other studied anions,
      and receptors 2 and 3 are sensitive for H(2)PO(4)(-) detection.

PMID- 19604130
TI  - Translational control of eukaryotic gene expression.
AB  - Translational control mechanisms are, besides transcriptional control and mRNA
      stability, the most determining for final protein levels. A large number of
      accessory factors that assist the ribosome during initiation, elongation, and
      termination of translation are required for protein synthesis. Cap-dependent
      translational control occurs mainly during the initiation step, involving
      eukaryotic initiation factors (eIFs) and accessory proteins. Initiation is
      affected by various stimuli that influence the phosphorylation status of both
      eIF4E and eIF2 and through binding of 4E-binding proteins to eIF4E, which finally
      inhibits cap- dependent translation. Under conditions where cap-dependent
      translation is hampered, translation of transcripts containing an internal
      ribosome entry site can still be supported in a cap-independent manner. An
      interesting example of translational control is the switch between cap
      independent and cap-dependent translation during the eukaryotic cell cycle. At
      the G1-to-S transition, translation occurs predominantly in a cap-dependent
      manner, while during the G2-to-M transition, cap-dependent translation is
      inhibited and transcripts are predominantly translated through a cap-independent
      mechanism.

PMID- 19604132
TI  - Glucose tolerance status in pregnancy: a window to the future risk of diabetes
      and cardiovascular disease in young women.
AB  - It has long been recognized that the diagnosis of gestational diabetes mellitus
      (GDM) identifies a population of young women at high risk of developing Type 2
      diabetes (T2DM) in the future. In recent years, however, a series of studies have
      revealed that antepartum glucose tolerance screening, a standard element of
      current obstetrical care instituted for the purpose of detecting GDM, may provide
      previously-unrecognized insight into a woman's future risk of metabolic and
      vascular disease. Indeed, it has emerged that in fact any degree of abnormal
      glucose tolerance detected on antepartum screening (i.e. not just GDM) predicts
      an increased future risk of pre-diabetes and diabetes, one that is proportional
      to the severity of dysglycemia observed in pregnancy. In addition, in the years
      following the index pregnancy, women with a history of GDM exhibit an enhanced
      cardiovascular risk profile and ultimately an increased incidence of
      cardiovascular disease (CVD), risks that may similarly extend to women with
      milder gestational glucose intolerance as well. Thus, by providing a unique
      window to a woman's risk potential for future metabolic and vascular disease,
      glucose tolerance testing in pregnancy, as currently practiced, may offer an
      opportunity for the early identification of high-risk individuals prior to the
      onset of clinical disease. Ultimately, the insight so derived may inform
      strategies for postpartum surveillance, risk factor modification, and disease
      prevention that may eventually lead to a reduction in the burden of T2DM and CVD
      in women.

PMID- 19604131
TI  - Label-free optical biosensor for probing integrative role of adenylyl cyclase in
      G protein-coupled receptor signaling.
AB  - Adenylyl cyclase is considered as an integrator for receptor signaling. However,
      its integrative role in receptor signaling is largely studied at the level of
      point of contacts in complex pathways. Here we used forskolin as a
      pharmacological probe and the resonant waveguide grating (RWG) biosensor to
      examine the signal integration of G protein-coupled receptors (GPCRs) at the
      cyclase-cyclic AMP-PKA module. The biosensor is a refractive index sensitive
      optical biosensor that is capable of detecting ligand-induced dynamic mass
      redistribution in cells without labels and cellular manipulations. Stimulation of
      seven cell lines with forskolin led to distinct optical responses, indicative of
      distinct expressions and/or organization of cyclase isoforms. The forskolin
      response in A431 was sensitive to the activities of protein kinase A, Rho kinase,
      and MAP kinases. Desensitization assays showed that the forskolin pretreatment
      heterologously desensitized G(s) signaling, partially attenuated G(q) signaling,
      but had complicate impacts on G(i) signaling. This study documents the
      integrative role of adenylyl cyclase in GPCR signaling and the power of forskolin
      as a pharmacological probe to differentiate receptor signaling using the label
      free biosensor cellular assays.

PMID- 19604133
TI  - Macronutrient specific postprandial oxidative stress: relevance to the
      development of insulin resistance.
AB  - The prevalence of obesity and its associated disorders [e.g., insulin resistance,
      type 2 diabetes and cardiovascular disease (CVD)] has seen a rapid increase in
      recent years. As such, understanding the mechanisms underlying diet-induced
      insulin resistance has been a topic of interest. In line with this notion,
      postprandial oxidative stress has received considerable attention over the past
      several years due to its involvement in the etiology of the above mentioned
      conditions. In fact, postprandial oxidative stress has been suggested to be the
      unifying mechanism in the connection between insulin resistance, Type 2 diabetes
      and CVD. In addition to this growing association, recent data are now available
      suggesting a causal role for such prooxidant stress in the development of insulin
      resistance. This review is intended to provide an overview of literature
      pertaining to the role of free radical production following feeding, as related
      to the development of insulin resistance, Type 2 diabetes and CVD.

PMID- 19604134
TI  - The mechanism of dead-in-bed syndrome and other sudden unexplained nocturnal
      deaths.
AB  - The mechanism of dead-in-bed syndrome (DBS), a rare but devastating condition
      that mainly affects young type 1 diabetes patients, remains mysterious. A new
      theory is proposed to explain this syndrome. This theory suggests that repeated
      episodes of hypoglycaemia-induced adaptation in orexin-A neurons cause (i)
      defective awakening and (ii) hypotonia of upper airway muscles during sleep.
      Consequently, due to the combined effect of these factors, long-term exposure of
      intermittent hypoxia occurs, leading to a combination of factors - such as
      depression of ventilation, increase in sympathetic tone, fluctuations in
      intrathoracic pressure and cardiac arrhythmias - these in conjunction with an
      underlying cardiovascular pathology (genetically inherited or acquired) cause
      cardio-respiratory failure and thus sudden death during sleep. This mechanism can
      be generalized to explain other cases of sudden unexplained nocturnal deaths
      including sudden infant deaths (SIDs).

PMID- 19604135
TI  - Elastic liposomes for topical and transdermal drug delivery.
AB  - Elastic vesicles have been developed and evaluated as novel topical and
      transdermal delivery systems. They are similar to conventional liposomes but with
      the incorporation of an edge activator in the lipid bilayer structure to provide
      elasticity. Elastic vesicles are applied non-occluded to the skin and have been
      shown to permeate through the stratum corneum lipid lamellar regions as a result
      of the hydration or osmotic force in the skin. They have been investigated as
      drug carriers for a range of small molecules, peptides, proteins and vaccines,
      both in vitro and in vivo. Following topical application, structural changes in
      the stratum corneum have been identified and intact elastic vesicles visualised
      within the stratum corneum lipid lamellar regions, but no intact vesicles have
      been identified in the deeper viable tissues. Their method of transporting their
      drug payload into and through the skin has been investigated but remains an area
      of contention. This review provides an overview of the development of elastic
      vesicles for delivery into and via the skin.

PMID- 19604136
TI  - Intravesical drug delivery into the bladder to treat cancers.
AB  - The standard treatment for patients with bladder cancer is surgical transurethral
      resection (TUR). Intravesical chemotherapy and immunotherapy are widely used
      after TUR to prevent recurrence and progression of superficial disease. There are
      many drug therapies for bladder cancer via intravesical instillation. This review
      describes the drugs which are approved or currently tested for treating bladder
      cancers. Some new chemotherapies and immunotherapies under investigation are also
      introduced. Vehicles to carry or encapsulate intravesical drugs are introduced in
      this review. Enhancement approaches to promote drug absorption or prolong
      residence times such as nano-sized particles, thermo-chemotherapy, and
      electromotive drug administration are also discussed. This review summarizes the
      information regarding intravesical therapy and its enhancement techniques. Recent
      developments of these drugs and their carriers for in vivo or clinical use are
      presented.

PMID- 19604137
TI  - Sustained release of diltiazem hydrochloride from chitosan micro-capsules.
AB  - The objective of the present study was to develop sustained release formulation
      of Diltiazem hydrochloride (DH) using biodegradable polymers. For this purpose
      microcapsules embedded Diltiazem hydrochloride were prepared using chitosan alone
      and also by incorporating some co polymers like methyl cellulose (MC), sodium
      carboxy methyl cellulose (SCMC) and poly vinyl pyrollidone (PVP) by employing
      complex emulsion method of microencapsulation. Glutaraldehyde saturated toluene
      solution is used as cross linking agent. Microcapsules were prepared in various
      core: coat ratios to know the effect of polymer and co polymers on drug release.
      Overall eight formulations were prepared and evaluated for flow behaviour, sieve
      analysis, drug entrapment efficiency, in vitro dissolution studies, stability
      studies, including scanning electron microscopy. The resulting microcapsules were
      discrete, large, spherical and also free flowing. The drug content in all the
      batches of microcapsules was found to be uniform. The release was depended on
      core: coat ratio and nature of the polymers. FTIR analysis revealed chemical
      integrity between diltiazem hydrochloride (DH), chitosan and between the
      copolymers. Among the three copolymers used methyl cellulose retarded the drug
      release more than the other two, hence the same formulation was subjected for in
      vivo studies. The drug release from the microcapsules was found to be following
      non fickian diffusion. Mechanism of drug release was diffusion controlled first
      order kinetics. Drug diffusion co efficient and correlation co efficient were
      also assessed using various mathematical models. In vivo result analysis of
      pharmacokinetic parameters revealed that t max of reference and test formulations
      were the same. From the study it was concluded that, sustained release Diltiazem
      hydro chloride microcapsules could be achieved with success using chitosan alone
      and also in combination with other biodegradable polymers.

PMID- 19604138
TI  - Conception and evaluation of sustained release polymeric matrix beads for
      enhanced gastric retention.
AB  - The present study was aimed at developing and evaluating polymeric beads with
      sustained drug release and prolonged gastric residence. The polymeric beads were
      prepared by solvent evaporation technique using Cellulose acetate (CA) as matrix
      former for model drug Ibuprofen (IBF) in 1% aqueous polyvinyl alcohol (PVA)
      solution as external phase. Effects of various formulation variables like drug
      polymer ratio, external phase viscosity, external phase volume, solvent ratio and
      processing variables like stirring speed, temperature of external phase, stirring
      time, and drying temperature on properties of beads were accessed. Drug polymer
      ratio was optimized to maximize the percent yield and drug content. Beads were
      characterized for shape, size, percent buoyancy, entrapment efficiency, floating
      time and in-vitro drug release. The scanning electron micrographs show a porous
      nature of beads thereby enabling them to float. When used alone, CA though formed
      good beads, drug entrapment efficiency was very low. To increase the drug
      entrapment, CA was partially substituted with Ethyl cellulose EC (up to 20%) to
      modulate drug entrapment efficiency and optimize the bead properties including
      drug release. Beads formed with higher viscous solution either formed
      agglomerates or dumbbell shaped structures. The optimized batches have uniform
      size distribution, remained buoyant for more than 18 hours and sustained the drug
      release up to 10 hours with diffusion through matrix being the main drug
      releasing mechanism.

PMID- 19604139
TI  - Radiopharmaceutical tracking of particles injected into tumors: a model to study
      clearance kinetics.
AB  - OBJECTIVES: Success of selective drug therapies depends on the drug's depot time
      in the target to treat. Depot time is currently being prolonged, using drug
      eluting beads or microspheres for selective internal radiation therapy. The
      purpose of this study was to establish a model for investigating the depot time
      of particles injected into tumors in relation to tumor vascularization and
      particle size. MATERIALS AND METHODS: An animal model with two different
      vascularized tumors (Walker Carcinoma 256 (hypervascularized) and Yoshida Sarcoma
      (hypovascularized)) was used. The tumors were implanted into the hind leg of
      Wistar rats. When the tumors reached 10-15mm, rhenium radiolabeled particles of
      25microm and 0.3microm were percutaneously injected into the tumors: large
      particles (Re-188 microspheres) in 10 hypo- and 10 hypervascularized tumors and
      small particles (Re-186 sulfid colloid) in 4 hypo- and 16 hypervascularized
      tumors with the co-injection of the vasoconstrictor, adrenalin (0.01 mg), into 8
      hypervascularized tumors. Tumor activity was measured with a gamma camera at 10
      min, 1h, 3h, 6h, 14h and 48h p.i. In addition, activity in the lung, liver,
      spleen, kidneys, and lymph nodes was measured at 48 h p.i. Measurements were
      adjusted for decay times and then compared. RESULTS: Drainage of the injected
      particles is bi-phasic, characterized by a fast wash-out. At 10 min p.i.,
      intratumoral activity decreases to 70% of the initially injected activity. This
      is followed by a slow decline at 48 h p.i in which intratumoral activity
      decreases to at least 60% of the initially injected activity. Slow decline is
      independent of particle size and vascularization, whereas fast leakage depends on
      both. Co-injecting adrenalin significantly reduced the wash-out of the small
      particles. Radiolabeled microspheres accumulated mainly in the lungs, smaller
      colloids in the liver. CONCLUSIONS: Particle stay time, biodistribution, and
      stability can be easily monitored as shown in this animal model. The
      hematogeneous wash-out can be reduced, using larger particles and
      vasoconstrictors. Prolonged retention is independent of vascularization and
      particle size and appears to be sufficient for therapy.

PMID- 19604140
TI  - Colloidal polymeric nanoparticles and brain drug delivery.
AB  - The blood brain barrier protects the brain from harmful substances in the blood
      stream and has stopped the development of many powerful and interesting drugs
      candidates for central nervous system due to the low poor distribution and by
      efflux mechanisms. Many different approaches have been developed in order to
      overcome this barrier and the drug gain access to the brain. The polymeric
      nanoparticles are efficient colloidal systems that have been investigated to the
      brain drug delivery. This review will focus on the current strategies for brain
      drug delivery emphasizing the properties and characteristics of polymeric
      nanoparticles for this purpose.

PMID- 19604141
TI  - Status of fatty acids as skin penetration enhancers-a review.
AB  - Novel techniques for drug delivery have been investigated in human medicine in
      recent years. The transdermal route of drug delivery has attracted researchers
      due to many biomedical advantages associated with it. However, excellent
      impervious nature of skin is the greatest challenge that has to be overcome for
      successfully delivering drug molecules to the systemic circulation by this route.
      One long-standing approach for improving transdermal drug delivery uses
      penetration enhancers (also called sorption promoters or accelerants) that can
      reversibly compromise the skin's barrier function and consequently allow the
      entry of otherwise poorly penetrating molecules into the membrane and through to
      the systemic circulation. A large number of fatty acids have been used as
      permeation enhancers. They have proven to be effective and safe sorption
      promoters. This present review includes the classification, feasibility and
      application of fatty acids as sorption promoters for improved delivery of drug
      through skin.

PMID- 19604142
TI  - Transdermal delivery of atenolol: effect of prodrugs and iontophoresis.
AB  - Inadequate skin permeability is the main challenge encountered in the transdermal
      drug delivery and to solve this crisis physical and chemical enhancement
      techniques are being developed. The aim of the present investigation was to study
      the combined effect of two such techniques, iontophoresis and esterification, on
      the transdermal delivery of atenolol. A series of ester prodrugs of atenolol were
      synthesized, characterized and studied for physicochemical properties and
      stability. In vitro permeation studies were carried out for atenolol and prodrugs
      at different donor concentrations (5, 10, and 20 mM) by passive process and
      iontophoresis (0.5 mA/cm(2)). Evaluation of the physicochemical parameters showed
      significant increase in lipophilicity and slight reduction in pK value in the
      ester prodrugs compared to parent drug. Stability studies revealed higher
      stability at pH 4 than pH 6. Prodrugs significantly enhanced the transdermal flux
      of atenolol in passive process while in iontophoresis the enhancement ranged from
      1.4 to 2.7 fold compared to atenolol. In the prodrug series, permeation rate
      increased with increase in the length of alkyl side chain up to the addition of 5
      carbon units, but thereafter no specific pattern was recorded in both passive and
      iontophoretic process. The steady state flux was highest in atenolol valerate
      (1.48 micromol/cm(2) h), which shows the promise of meeting the desired
      permeation rate (3.0- 31.0 micromol/ h) for maintenance of the therapeutic level
      in a 70 kg human.

PMID- 19604143
TI  - Development of extended release divalproex sodium tablets containing hypdrophobic
      and hydrophilic matrix.
AB  - Bilayered tablets of Divalproex sodium for once-a-day administration were
      prepared using a hydrophilic and hydrophobic polymer as release retarding agents.
      This technology was found to be more effective than a simple matrix tablet with a
      mixture of the above polymers in order to retard the drug release for a period of
      24 h. The drug release profile was strongly dependent on the presence of wicking
      agent, pathlength of hydrophobic layer, and hardness of tablet. f(1) value of
      6.92 and f(2) value of 76.72 indicated similarity between the release profiles of
      batch BT3 and reference tablet (Depakote((R)) ER) with the target release of over
      55% within 12 h and over 85% within 18 h. Mathematical modeling using Korsmeyer
      Peppas equation indicated that the release followed a combination of diffusion
      and erosion mechanism.

PMID- 19604144
TI  - Evaluation of a diphtheria and tetanus PLGA microencapsulated vaccine formulation
      without stabilizers.
AB  - Polymeric microspheres containing diphtheria and tetanus toxoids were prepared
      without protein stabilizers. A vaccine containing 2 Lf(tetanus) and 0.4
      Lf(diphtheria) was injected either in BALB/c mice or in guinea-pigs. As control,
      a group received the alum-adsorbed unencapsulated toxoids. In mice, on day 44 one
      group and control received a booster and at day 111 the other group received the
      same booster dose. Before de booster, all groups had very low neutralizing
      antibodies, as determined by Toxin binding inhibition assay. One week after
      booster all groups had high antibody titers, especially those immunized with
      microencapsulated vaccine, which were at least 5 times higher than those
      immunized with alum vaccine for both antigens. Besides, guinea pigs receiving
      lower dose had antibodies titers as high as 60 UI/mL, and 30 times higher than
      those immunized with alum vaccine. Therefore by using an encapsulated vaccine
      without any kind of protein stabilizer we were able to induce in vivo protective
      responses irrespective of observed in vitro protein degradation by HPLC.
      Manipulating the vaccination schedule at the same time to the toxoids
      encapsulation does not only increase the antibody titers but also their
      specificity.

PMID- 19604145
TI  - L(9) orthogonal design assisted formulation and evaluation of chitosan-based
      buccoadhesive films of miconazole nitrate.
AB  - The present study was aimed to prepare and evaluate buccoadhesive films of
      miconazole nitrate (MCZ). The films based on chitosan were prepared by solvent
      casting method using L(9) orthogonal array design to release the drug above its
      minimum inhibitory concentration (MIC) for a prolonged period of time so as to
      reduce its frequency of administration. As per the experimental design, guar gum,
      HPMC K15M and HEC were added at three different levels to control the drug
      release. Films showed smooth, uniform and non-sticky surface with good
      flexibility and folding endurance. Thickness and weight-variation data showed no
      significant difference among the batches, indicating that the polymeric blend
      possessed a good film forming ability and its desired properties could easily be
      achieved by varying the composition of the casting solution. Films composed of
      chitosan with guar gum appeared to be tougher; comparatively more bioadhesive in
      vitro, resided to an appropriate time interval and swelled at a more reasonable
      rate than those containing HPMC and HEC, suggesting the superiority of guar gum
      over other polymers. In vitro drug release studies conducted on all batches and
      microbiological studies done on the statistically optimized formulation
      demonstrated that the films had ability to sustain the drug concentration above
      its MIC for 6 hrs, despite the incorporation of a smaller dose (2.5 mg/cm(2) of
      the film). Films, except CF2 and CF3, followed Fickian diffusion of release
      mechanism. FT-IR spectra revealed no interactions between the drug and polymers.

PMID- 19604146
TI  - Propofol pharmacokinetics in patients with obstructive jaundice.
AB  - The effect of obstructive jaundice on the distribution and elimination of
      propofol was studied in 15 patients with obstructive jaundice (total serum
      bilirubin, TBL >/= 17.1micromol.l(-1)) and in 15 control patients (TBL <
      17.1micromol.l(-1)). Following an i.v. bolus dose of propofol (2-2.5 mg.kg(-1))
      multiple arterial samples were obtained at timed intervals for 4 h and blood
      concentrations of propofol were measured by high pressure liquid chromatography.
      Compartmental analysis of propofol concentrations revealed a three-compartment
      model with elimination from a central compartment in all patients.
      Pharmacokinelic parameters: volumes of distribution at steady state (V(SS)),
      volumes of distribution at equilibrium (V(r)), volumes of the central compartment
      (V) and total body clearance (Cl) were similar in patients with obstructive
      jaundice (mean 12.3 (SD 6.0) litre.kg(-1), 32.99(21.42) litre.kg(-1),
      0.241(0.131) litre.kg(-1), and 28.8(8.2) ml.min(-1).kg(-1) respectively) compared
      with contro1 group (11.9 (5.4) litre.kg(-1), 28.30(13.70) litre.kg(-1),
      0.297(0.112) litre.kg(-1), and 33.9(7.6) ml.min(-1).kg(-1) respectively)
      (P>0.05). Half-times of the three phases
      (T(1/2)(alpha),T(1/2)(beta),T(1/2)(gamma)) were also similar between both
      groups.We conclude that in patients with obstructive jaundice the
      pharmacokinetics of propofol are similar to those of patients without obstructive
      jaundice.

PMID- 19604147
TI  - Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-induced cell
      death by modulating JNK activation.
AB  - MST3 (mammalian sterile 20-like kinase 3) is a sterile 20 kinase reported to have
      a role in Fas-ligation- and staurosporine-induced cell death by unknown
      mechanism(s). We found that MST3-deficient cells are resistant to H2O2, which was
      reversed by reconstituting recombinant MST3. H2O2-induced JNK (c-Jun N-terminal
      kinase) activation was greatly enhanced in shMST3 cells (a cell line treated with
      short hairpin RNA against MST3). Suppression of JNK activity by the inhibitor
      SP600125 or by dominant-negative JNK2 re-sensitized cells to H2O2. Furthermore, c
      Jun Ser-63 phosphorylation was augmented in shMST3 cells, whereas JunAA (dominant
      negative c-Jun) reduced H2O2 resistance, implicating an AP-1 (activator protein
      1) pathway in H2O2-induced survival signalling. Total cytoprotective HO-1 (haem
      oxygenase 1) expression, which was attenuated by JunAA, was induced up to 5-fold
      higher in shMST3 cells compared with controls. Zinc protoporphyrin IX, a potent
      inhibitor of HO reversed the H2O2-resistance of shMST3 cells. Our results reveal
      that H2O2-induced MST3-mediated cell death involves suppressing both a JNK
      survival pathway and up-regulation of HO-1.

PMID- 19604148
TI  - High ambient glucose induces angiotensin-independent AT-1 receptor activation,
      leading to increases in proliferation and extracellular matrix accumulation in
      MES-13 mesangial cells.
AB  - Diabetic nephropathy is associated with mesangial ECM (extracellular matrix)
      accumulation. We have shown that AT-1R [Ang II (angiotensin II) type I receptor]
      signalling induces ECM proteins via transactivation of PI3K (phosphoinositide 3
      kinase) in mesangial cells. In the present study, we examined the mechanisms
      underlying the effect of high ambient glucose on cell proliferation and ECM
      expansion in a mesangial context. High glucose induced increases in PI3K
      activity, proliferation and ECM accumulation in mesangial cells. These effects
      were abrogated by losartan, an AT-1R antagonist, but not by [Sar1,Thr8]-Ang II
      (Sar is sarcosine), an inactive analogue of Ang II, or by a neutralizing antibody
      against Ang I/II. Overexpression of a constitutively active PI3Kalpha or AT-1R
      alone was sufficient to induce similar changes by high glucose. In contrast,
      overexpression of an inactive AT-1R lowered the basal levels and rendered the
      cells non-responsive to high glucose. Moreover, cells overexpressing wild-type AT
      1R had enhanced sensitivity to acute Ang II stimulation. These cells, however,
      did not respond to conditioned medium obtained from mesangial cells cultured in
      high glucose. We further demonstrated that iAng (intracellular Ang II) can be
      induced by high glucose but only under certain conditions. Efficient suppression
      of iAng by short hairpin RNA against angiotensinogen, however, did not affect
      high glucose-induced effects on MES-13 cells. These results suggest that high
      ambient glucose induces activation of AT-1R in an Ang II-independent manner to
      transactivate PI3K, resulting in proliferation and ECM accumulation in mesangial
      cells.

PMID- 19604149
TI  - Mapping of the ligand-binding site on the b' domain of human PDI: interaction
      with peptide ligands and the x-linker region.
AB  - PDI (protein disulfide-isomerase) catalyses the formation of native disulfide
      bonds of secretory proteins in the endoplasmic reticulum. PDI consists of four
      thioredoxin-like domains, of which two contain redox-active catalytic sites (a
      and a'), and two do not (b and b'). The b' domain is primarily responsible for
      substrate binding, although the nature and specificity of the substrate-binding
      site is still poorly understood. In the present study, we show that the b' domain
      of human PDI is in conformational exchange, but that its structure is stabilized
      by the addition of peptide ligands or by binding the x-linker region. The
      location of the ligand-binding site in b' was mapped by NMR chemical shift
      perturbation and found to consist primarily of residues from the core beta-sheet
      and alpha-helices 1 and 3. This site is where the x-linker region binds in the X
      ray structure of b'x and we show that peptide ligands can compete with x binding
      at this site. The finding that x binds in the principal ligand-binding site of b'
      further supports the hypothesis that x functions to gate access to this site and
      so modulates PDI activity.

PMID- 19604150
TI  - Specific role of phosphoinositide 3-kinase p110alpha in the regulation of
      phagocytosis and pinocytosis in macrophages.
AB  - PI3K (phosphoinositide 3-kinase) alpha has been implicated in phagocytosis and
      fluid-phase pinocytosis in macrophages. The subtype-specific role of PI3K in
      these processes is poorly understood. To elucidate this issue, we made Raw 264.7
      cells (a mouse leukaemic monocyte-macrophage cell line) deficient in each of the
      class-I PI3K catalytic subunits: p110alpha, p110beta, p110delta and p110gamma.
      Among these cells, only the p110alpha-deficient cells exhibited lower
      phagocytosis of opsonized and non-opsonized zymosan. The p110alpha-deficient
      cells also showed the impaired phagocytosis of IgG-opsonized erythrocytes and the
      impaired fluid-phase pinocytosis of dextran (molecular mass of 40 kDa). Receptor
      mediated pinocytosis of DiI (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate)-labelled acetylated low-density
      lipoprotein and fluid-phase pinocytosis of Lucifer Yellow (molecular mass of 500
      Da) were resistant to p110alpha depletion. None of these processes were impaired
      in cells lacking p110beta, p110delta or p110gamma, but were susceptible to a pan
      PI3K inhibitor wortmannin. In cells deficient in the enzymes catalysing
      PtdIns(3,4,5)P3 breakdown [PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) or SHIP-1 (Src-homology-2-domain-containing inositol phosphatase
      1)], uptake of IgG-opsonized particles was enhanced. These results indicated that
      phagocytosis and fluid-phase pinocytosis of larger molecules are dependent on the
      lipid kinase activity of p110alpha, whereas pinocytosis via clathrin-coated and
      small non-coated vesicles may depend on subtypes of PI3Ks other than class I.

PMID- 19604151
TI  - Monitoring severe hypoglycaemic episodes: sample bias?

PMID- 19604152
TI  - Ehlers-Danlos syndrome.

PMID- 19604154
TI  - Ocular involvement in paediatric haemolytic uraemic syndrome.
AB  - PURPOSE: The aim of this study was to estimate the frequency and severity of
      ocular involvement in paediatric patients with haemolytic uraemic syndrome (HUS).
      METHODS: The study was designed as an institutional, retrospective, observational
      case series. Charts for all 87 paediatric patients with HUS treated at the
      University Children's Hospital Zurich between 1995 and 2007 were reviewed.
      Patients with ocular involvement were identified and clinical findings presented.
      RESULTS: Three of 69 examined patients with HUS showed ocular involvement.
      Ophthalmic findings in two children were consistent with bilateral Purtscher
      retinopathy, showing multiple haemorrhages, exudations and superficial retinal
      whitening. The third child presented with bilateral isolated central intraretinal
      haemorrhages as a milder form of ocular involvement. In one of the children with
      Purtscher retinopathy, laser photocoagulation was required for bilateral rubeosis
      irides and development of disc neovascularization. Longterm outcomes in the two
      severely affected children showed decreased visual acuity caused by partial
      atrophy of the optic nerves. In the milder case visual acuity was not impaired at
      any time. CONCLUSIONS: A minority of paediatric patients with HUS developed
      ocular involvement. Acute ocular findings varied in severity from isolated
      intraretinal haemorrhages to Purtscher-like retinopathy with retinal ischaemia.
      Longterm complications included the development of neovascularizations and
      consecutive optic nerve atrophy. Although ocular involvement in HUS seems to be
      rare, physicians should be aware of this complication because of its possible
      vision-endangering consequences.

PMID- 19604155
TI  - Intraocular lymphoma diagnosed by fine-needle aspiration biopsy.
AB  - PURPOSE: To describe clinical experience in the diagnosis of intraocular lymphoma
      by fine-needle aspiration biopsy (FNAB) in patients with one or more discrete
      intraocular infiltrative lesions and limited or absent intravitreal tumour cells.
      METHODS:  Retrospective descriptive analysis of patients who underwent
      intraocular FNAB of a solid retinal, subretinal pigment epithelial or uveal
      tumour that proved to be a malignant lymphoma. RESULTS: After exclusions, our
      study group consisted of seven patients, each of whom had one or more discrete
      intraocular infiltrative lesions and limited or absent intravitreal tumour cells
      and underwent a diagnostic intraocular FNAB that confirmed malignant intraocular
      lymphoma cytopathologically. These included three patients with one or more
      geographic yellow subretinal pigment epithelial infiltrates and one patient each
      with a prominent nodular white subretinal pigment epithelial tumour, a rapidly
      developing solid placoid choroidal mass, a haemorrhagic retinal infiltrative
      lesion and an infiltrative iris tumour, respectively. A prominent feature of
      virtually all aspirates was a large proportion of degenerated lymphoid cells in
      the background. Cytologically intact tumour cells ranged from relatively
      homogeneous small round cells with large nucleus to cytoplasm ratio to
      pleomorphic large cells with irregular knob-like nuclear protrusions.
      Immunocytochemical stains for lymphoid markers were helpful in confirming the
      pathological diagnosis of lymphoma in the five patients in whom this testing was
      performed. CONCLUSION: FNAB was a useful diagnostic tool in the described
      subgroup of patients with suspected intraocular lymphoma. FNAB should be
      considered as a diagnostic option in selected patients with suspected intraocular
      lymphoma, especially if there are few or no vitreous cells.

PMID- 19604156
TI  - Intravitreal autologous bone-marrow-derived mononuclear cell transplantation.

PMID- 19604157
TI  - Sudden bilateral corneal oedema in a patient with Parkinson's disease.

PMID- 19604158
TI  - Adenosine receptor protein changes in guinea pigs with form deprivation myopia.
AB  - PURPOSE: Recent results have shown that treatment with the non-selective
      adenosine antagonist 7-methylxanthine (7-MX) reduces the development of form
      deprivation myopia (FDM) in guinea pigs. The aims of this study were to identify
      the presence of adenosine receptors (AdoRs) in the eye wall of the guinea pig and
      to determine their possible changes during form deprivation. METHODS: Three-week
      old guinea pigs were monocularly treated with a translucent lens to induce FDM.
      After 21 days, samples were taken from the posterior eye wall and examined with
      immunofluorescence confocal microscopy for the presence of AdoRA1, AdoRA2A,
      AdoRA2B and AdoRA3 proteins. Western blot analysis was used to quantitate AdoRs
      in samples from the retina, choroids and sclera. RESULTS: All four subtypes of
      AdoR were expressed in the posterior wall of the guinea pig eye, although AdoRA3
      only weakly. Twenty-one days after the induction of myopia, we observed a
      significant decrease in protein expression for AdoRA1 (- 25.5%) and an increase
      in protein expression for AdoRA2B (+ 66.7%) in the retina of FDM eyes.
      CONCLUSIONS: AdoRs of all subtypes are expressed in the retina, choroids and
      sclera in guinea pigs and may play a role in the regulation of eye growth. The
      changed pattern of AdoR expression during form deprivation confirms that
      pharmaceutical intervention targeting AdoRs may reduce myopia progression.

PMID- 19604159
TI  - Jamming of 23-gauge instruments in the microcannula during vitrectomy for severe
      vitreous haemorrhage.

PMID- 19604160
TI  - Retinal pigment epithelium tears after intravitreal injection of ranibizumab for
      predominantly classic neovascular membranes secondary to age-related macular
      degeneration.
AB  - PURPOSE: Retinal pigment epithelium (RPE) tear is an extremely rare complication
      in patients with classic neovascular membranes without RPE detachment. We
      evaluate their incidence and functional outcome following treatment with
      intravitreal ranibizumab. METHODS: Observational study of 72 consecutive patients
      (74 eyes) treated at Jules Gonin University Eye Hospital, Lausanne, with
      intravitreal ranibizumab 0.5 mg for classic choroidal neovascularization (CNV)
      between March 2006 and February 2008. Best-corrected visual acuity (BCVA), fundus
      examination and optical coherence tomography were recorded monthly; fluorescein
      angiography was performed at baseline and repeated at least every 3 months.
      RESULTS: RPE tears occurred in four (5.4%) eyes temporal to the fovea, after a
      mean of four injections (range 3-6). Mean baseline BCVA was 0.25 decimal
      equivalent (logMAR 0.67) and improved despite the RPE tear to 0.6 decimal
      equivalent (logMAR 0.22). CONCLUSION: RPE tears following intravitreal
      ranibizumab injections for classic CNV can occur in about 5% of patients, even in
      the absence of baseline RPE detachment. Nevertheless, vision may improve provided
      the fovea is not involved.

PMID- 19604161
TI  - Topography of solitary congenital hypertrophy of the retinal pigment epithelium
      in the ocular fundus.

PMID- 19604162
TI  - Metabonomics--a new approach in ophthalmology.
AB  - Metabonomics is a new technology providing broad information about dynamic
      metabolic responses in living systems to pathophysiological stimuli or genetic
      modification. Nuclear magnetic resonance (NMR) spectroscopy is one of the most
      powerful methods in metabonomics; it is utilized to establish the metabolic
      profiles of biofluids, and is practically the only method capable of examining
      intact tissue samples. Experience with the application of metabonomics in eye
      research is still limited, yet this method provides the possibility of exploring
      metabolic processes in the eye in vivo. This article presents a brief background
      to the usefulness of metabonomics, and the possible applications of an NMR-based
      technique in eye research and clinical practice.

PMID- 19604163
TI  - Organ culture, but not hypothermic storage, facilitates the repair of the corneal
      endothelium following mechanical damage.
AB  - PURPOSE: To evaluate the reparative capacity of the mechanically injured
      endothelium of corneas stored under organ culture (OC) or hypothermic conditions.
      METHODS: The central endothelium of 12 pairs of human corneas with similar
      endothelial parameters was damaged to create a 1 mm(2) lesion. One cornea from
      each pair was stored under OC and one under hypothermic conditions. The
      endothelial cell density (ECD), coefficient of variation, hexagonality and
      percentage of dead cells were assessed before and after damage and on days 7, 14,
      21 and 28 of storage. RESULTS: The mean ECD of corneas subsequently stored under
      OC or hypothermic conditions was 2764/mm(2). Immediately after damage, a denuded
      Descemet's membrane with a few remaining dead cells was observed at the injured
      area. After 7 days of storage under OC conditions, almost no dead cells were
      observed at the place of injury. A non-significant worsening of the qualitative
      parameters (polymegatism and pleomorphism) was found. After 14 days, ECD was
      1933/mm(2) and 2478/mm(2) centrally and pericentrally, respectively. Similar
      values were found after 21 and 28 days of storage. The lesions with remnant dead
      cells persisted throughout hypothermic preservation. From day 14 the corneas
      became cloudy and in poor condition, while the pericentral ECD was 2523/mm(2).
      CONCLUSION: The reparative capacity of the cornea is maintained under OC but not
      under hypothermic conditions. For corneas containing dead endothelial cells, OC
      is therefore the method of choice because it may improve the quality of the
      stored tissue.

PMID- 19604164
TI  - Interactions between vitreous-derived cells and vascular endothelial cells in
      vitreoretinal diseases.
AB  - PURPOSE: This study aimed to investigate the roles played by vitreous-derived
      cells in the pathogenesis of vitreoretinal vascular diseases. METHODS: The
      vitreous was removed from porcine eyes and small pieces were cultured from which
      vitreous-derived cells were isolated. Polymerase chain reaction and ELISA were
      performed to determine the expression of vascular endothelial growth factor
      (VEGF) and interleukin 6 (IL-6) at the mRNA and protein levels, respectively. The
      viability of human retinal endothelial cells (HRECs) exposed to vitreous-derived
      cells was assessed by MTT assay. RESULTS: Expression of the mRNA and protein of
      VEGF and IL-6 was increased by exposing the porcine vitreous-derived cells
      (PVDCs) to interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta) and
      tumour necrosis factor alpha (TNFalpha), but not to VEGF or IL-6. The percentage
      of living human vascular endothelial cells was increased by including VEGF and IL
      6 in the culture media. The viability of HRECs was affected by co-culturing them
      with PVDCs that had been exposed to IL-1alpha, IL-1beta, IL-6, TNFalpha and VEGF.
      CONCLUSIONS: Porcine vitreous-derived cells are stimulated by IL-1alpha, IL-1beta
      and TNFalpha, and produce VEGF and IL-6, which then enhance the proliferation of
      vascular endothelial cells. This network, including the cytokines and different
      types of cells, may contribute to the pathogenesis of proliferative vitreoretinal
      diseases.

PMID- 19604165
TI  - Risk of retinal neovascularization in the second eye in patients with
      proliferative diabetic retinopathy.
AB  - PURPOSE: This study aimed to evaluate the risk of proliferative diabetic
      retinopathy (DR) in the fellow eye of an eye with existing proliferative DR.
      METHODS: Our DR screening programme database listed 1513 diabetes patients alive
      at the time of the study. Seventy-six had proliferative DR in one or both eyes.
      RESULTS: In 28 of the 76 (37%) diabetes patients, proliferative DR was diagnosed
      in both eyes at the same examination. Another 28 patients developed proliferative
      DR in the second eye within 5 years of its diagnosis in the first eye, bringing
      the total number of diabetes patients with proliferative DR in both eyes at 5
      years to 56 (74%). Almost all the diabetes patients eventually developed
      proliferative DR in the second eye. The median duration of diabetes before the
      development of proliferative retinopathy was 19 years for type 1 and 14 years for
      type 2 diabetes. CONCLUSIONS: Proliferative DR is a bilateral disease. Diabetes
      patients with proliferative DR in one eye are at high risk of developing
      neovascularization in the second eye and close follow-up is recommended.

PMID- 19604166
TI  - Molecular identification of coliform bacteria from colicky breastfed infants.
AB  - OBJECTIVE: To determine the presence of intestinal coliform bacteria in colicky
      vs healthy infants. STUDY DESIGN: We isolated coliform strains from faeces and
      performed quantitative bacterial cultures in 41 colicky and 39 healthy breastfed
      infants, identified using PCR with species-specific primers, strain-specific
      Automated Ribotyping and the API-50E kit for Enterobacteriaceae to identify the
      most frequent strains. RESULTS: Coliform strains were more abundant in colicky
      infants (median 6.04 log(10) CFU/g faeces, range 2.00-8.76) vs controls (median
      4.47 log(10) CFU/g faeces, range 1.00-8.08) (p = 0.026). Escherichia coli,
      Klebsiella pneumoniae, K. oxytoca, Enterobacter cloacae, E. aerogenes and
      Enterococcus faecalis were the predominant species in colicky and healthy
      infants. The counts of each bacterial species differed between the two groups,
      and the difference was significant (p = 0.002) for E. coli: median 6.30 log(10)
      CFU/g faeces (range 3.00-8.74) in colicky infants, and median 4.70 log(10) CFU/g
      faeces (range 2.00-5.85) in controls. CONCLUSIONS: This is the first study to
      evaluate the colonization patterns of gas-forming coliforms in colicky infants
      and healthy controls identified by molecular methods. Coliform bacteria,
      particularly Escherichia coli, were found to be more abundant in colicky infants.
      Our data could help to shed light on the cause of infantile colic.

PMID- 19604167
TI  - Early cytomegalovirus infection and the long-term outcome of biliary atresia.
AB  - AIM: To study the impact of ongoing cytomegalovirus (CMV) infection at
      presentation of biliary atresia (BA) on the long-term outcome after Kasai
      procedure. METHODS: Twenty-eight patients with BA born 1988-1997 were included
      and followed-up until 2007. Eleven patients (group A) had ongoing CMV infection
      at presentation and were compared to the remaining 17 patients (group B). Median
      age at Kasai procedure was 75 days in group A and 70 days in group B (p = 0.12).
      RESULTS: Including all patients, survival with native liver was 50% and 36% at 4
      and 10 years of follow-up respectively. At the end of follow-up, it was 25% and
      overall survival was 68%. When comparing groups A and B, neither difference in
      survival with native liver (p = 0.67, log-rank test) nor in survival after liver
      transplantation was detected. CONCLUSION: Survival with native liver after Kasai
      procedure is comparable to that of other centres. CMV positive patients may
      present with a later onset, alternatively the detection of CMV infection could
      delay the referral of BA patients. No significant differences in long-term
      outcome were detected with regard to early CMV infection.

PMID- 19604168
TI  - Protein C concentrate in preterm neonates with sepsis.

PMID- 19604169
TI  - Bronchomalacia occurring in monozygotic twins--further information about its
      inheritance.
AB  - We report left main-stem bronchomalacia occurring in monozygotic twins that
      became symptomatic during infancy. This phenomenon has not previously been
      reported to occur in twins. Little is known about the aetiology of primary
      bronchomalacia, but this occurrence suggests that there may be a significant
      genetic component in some cases. CONCLUSION: Left main-stem bronchomalacia
      occurring in monozygotic twins suggests that there may be a significant genetic
      component in some cases and provides further information about the inheritance of
      this condition.

PMID- 19604170
TI  - Neonatal morbidity in late preterm and term infants in the nursery of a tertiary
      hospital.

PMID- 19604172
TI  - Independence in the toilet activity in children and adolescents with 
      myelomeningocele--managing clean intermittent catheterization in a  hospital
      setting.
AB  - AIM: The aim of this study was to identify and describe gross motor, fine motor,
      executive and time-processing obstacles for independence in children with
      myelomeningocele who are treated with Clean Intermittent Catheterization and to
      relate their opinions about their performance in the toilet activity, and their
      medical records, to the observed outcome. METHODS: In a hospital setting, 22
      children with myelomeningocele were observed using a structured information form
      while performing their toilet activity, and tested for time processing ability
      with the Ka-Tid instrument. RESULTS: Only five children were independent, despite
      the fact that 12 of 22 children were completely satisfied with their toilet
      activity. Neither the degree of motor impairment, nor sex or age had any
      significant impact on performing the toilet activity. The ability to remain
      focused on the toilet activity proved to have no relation to age or learning
      disabilities. The medical records for the children were only able to classify
      approximately three quarters correctly with respect to independence. The only
      measurement that could suggest anything in relation to a maintained focus was
      time processing ability. CONCLUSION: The children were unaware of their abilities
      and limitations. Time processing ability and observations are important factors
      to assess independence.

PMID- 19604173
TI  - Viewing and attention in children.

PMID- 19604174
TI  - Population-based waist circumference and waist-to-height ratio reference values
      in preschool children.
AB  - AIM: To establish new reference values for measurements of waist circumference
      and waist-to-height ratio in preschool children. METHODS: A population-based,
      cross-sectional study of 4502 children aged 0-5 years derived from child health
      care in a Swedish county. Measurements of weight, height and waist circumference
      were recorded using a standardized procedure. RESULTS: New reference values for
      waist circumference and waist-to-height ratio for preschool children are
      presented. Reference charts were constructed and are presented. Waist
      circumference increased with age (r = 0.80, p < 0.001). After adjustment to the
      individual height, expressed as waist-to-height ratio, there was an inverse
      correlation to age during the first 5 years of age (r = -0.87, p < 0.001).
      CONCLUSION: The new reference values for waist circumference and waist-to-height
      ratio for Swedish preschool children enable future identification of new risk
      populations for childhood obesity. For clinicians, new reference charts for these
      two variables are provided for practical use.

PMID- 19604176
TI  - High prevalence of impaired fasting glucose in Chinese children and adolescents
      with prehypertension/hypertension.
AB  - AIM: To assess the prevalence of impaired fasting glucose among Chinese children
      and adolescents with prehypertension/hypertension (PHP/HP), overweight/obesity
      (OW/OB) or both in the general population. METHODS: In total, 3409 children and
      adolescents among the age group of 10-18 years were enrolled. These subjects were
      then divided into four groups: OW/OB, PHP/HP, OW/OB + PHP/HP and a control group.
      Fasting plasma glucose (FPG) and lipid levels were measured in children with a
      body mass index > or =85th percentile and/or blood pressure > or =90th percentile
      and in 100 subjects randomly selected from the control group. The oral glucose
      tolerance test was performed in all the subjects with fasting glucose > or =5.6
      mmol/L. RESULTS: Eighty-one impaired fasting glucose subjects and one girl with
      type 2 diabetes were identified. The prevalence of impaired fasting glucose in
      PHP/HP (7.03%) was not significantly different from that in the OW/OB + PHP/HP
      group (8.59%), but was higher than that in the OW/OB group (3.31%). CONCLUSION:
      Although the American Diabetes Association does not recommend the FPG test for
      children and adolescents with PHP/HP, in this study, we found that children and
      adolescents with PHP/HP have a higher prevalence of impaired fasting glucose than
      those with OW/OB. Further validation of these findings is warranted and a type 2
      diabetes screening protocol for Chinese children and adolescents needs to be
      established.

PMID- 19604177
TI  - Ascites improves upon [corrected] serum sodium plus [corrected] model for end
      stage liver disease (MELD) for predicting mortality in patients with advanced
      liver disease.
AB  - BACKGROUND: The clinical impact of ascites has historically been well recognized;
      however, its value is unclear in the context of current prognostic models. AIM:
      To determine whether ascites can improve risk discrimination beyond model for end
      stage liver disease (MELD) and serum sodium (MELDNa). METHODS: Consecutive
      cirrhotic patients were evaluated for ascites on the basis of an outpatient CT
      along with concurrent MELD and Na values. Cox models were used to determine the
      added value of ascites for predicting 1-year mortality. Increases in the C-index,
      integrated discrimination improvement (IDI) and the net reclassification index
      (NRI) were used to assess improvements in discrimination after the addition of
      ascites. RESULTS: A total of 1003 patients had Na and MELD scores available
      within 30 days of the CT scan. A total of 60 deaths occurred within 1 year, with
      mortality higher in patients with ascites (21.4% vs. 4.0%, HR 6.08, 95% CI 3.62
      10.19, P < 0.0005). In the presence of ascites, the MELD and MELDNa scores
      underestimated mortality risk when the scores were less than 21. The addition of
      ascites to the MELDNa model substantially improved discrimination by the C-index
      (0.804 vs. 0.770, increase of 3.4%, 95% CI 0.2-9.9%), IDI (1.8%, P = 0.016) and
      NRI (15.8%, P = 0.0006). CONCLUSION: The incorporation of radiographic ascites
      significantly improves upon MELDNa for predicting 1-year mortality. The presence
      of ascites may help identify patients at increased risk for mortality, not
      otherwise captured by either MELD or MELDNa.

PMID- 19604178
TI  - Analysis of drug resistance and virulence-factor genotype of Irish Helicobacter
      pylori strains: is there any relationship between resistance to metronidazole and
      cagA status?
AB  - BACKGROUND: Helicobacter pylori infection is eradicated with antimicrobial agents
      and drug-resistant strains make successful treatment difficult. Geographical
      variations in virulence-factor genotype also exist. AIM: To evaluate prevalence
      of drug resistance and virulence-factor genotype in Irish H. pylori strains and
      to investigate if there is any relationship between drug resistance and genotype.
      METHODS: Helicobacter pylori strains isolated from 103 patients were examined.
      Antimicrobial susceptibilities were tested by Etest. The virulence-factor
      genotypes were determined using PCR. Frequencies of spontaneous metronidazole
      resistance were measured in vitro. RESULTS: Metronidazole resistance was present
      in 37.9% of strains examined. 16.5% of strains were clarithromycin-resistant and
      resistance to both agents observed was found in 12.6% of strains. 68% of strains
      were cagA(+). The dominant vacA type was s1/m2, followed by s1/m1 and s2/m2. The
      metronidazole resistance rate in cagA(-) group was significantly higher than in
      cagA(+) (P = 0.0089). Spontaneous resistance to metronidazole in cagA(-) occurred
      in higher frequency when compared with cagA(+). CONCLUSIONS: cagA(+) and
      vacAs1/m2 type was the dominant genotype in Irish H. pylori strains. Significant
      rates of metronidazole resistance were observed in cagA(-) group. cagA(-) strains
      tend to acquire metronidazole resistance in vitro. Absence of cagA might be a
      risk factor in development of metronidazole resistance.

PMID- 19604179
TI  - Serum HCV RNA levels and HCV genotype do not affect insulin resistance in
      nondiabetic patients with chronic hepatitis C: a multicentre study.
AB  - BACKGROUND: Chronic hepatitis C (CHC) induces insulin resistance (IR) and
      subsequently diabetes. AIM: To examine viral, metabolic and histological
      predictors of IR in 275 CHC patients to test the hypothesis that IR differs among
      HCV genotypes and that viral replication directly affects IR. METHODS: We studied
      275 nondiabetic treatment-naive CHC patients. Histological lesions were evaluated
      according to Ishak. IR was assessed using homeostasis model assessment for
      insulin resistance (HOMA-IR). RESULTS: HOMA > 3.0 was found in 37% of patients,
      independently associated with higher BMI and GGT. In genotype non-3 patients,
      HOMA > 3.0 was associated with higher BMI and GGT values, while no significant
      association was noted in genotype 3 patients. In non-obese patients with minimal
      fibrosis, HOMA > 3.0 was found in 20% of cases without significant differences
      among genotypes. No association between HOMA > 3.0 and HCV-RNA levels was found.
      Severe fibrosis (stage 5-6) related to older age (OR:1.048), HOMA-IR (OR:1.177),
      necroinflammation (OR: 2.990) and higher ALT (OR: 1.009) and GGT (OR:1.006).
      CONCLUSIONS: IR develops at early stages of CHC without significant differences
      among genotypes. It is more frequent in obese patients with steatosis and
      contributes to fibrosis progression. However, IR does not seem to be associated
      with viraemia and therefore its exact pathogenetic mechanism in CHC remains
      elusive.

PMID- 19604180
TI  - Clinical trial: long-term use of proton pump inhibitors in primary care patients 
      a cross sectional analysis of 901 patients.
AB  - BACKGROUND: The use of proton pump inhibitors (PPIs) is extensive. While the
      incidence of new treatments remains stable, the prevalence of long-term treatment
      is rising. Studies have shown that up to 70% of patients on chronic acid
      suppression lack a verified indication for treatment. AIMS: To investigate
      primary care patient characteristics associated with long-term use of PPIs.
      METHODS: A cross-sectional analysis of 42,634 patients registered with 22 general
      practitioners was performed. Patients with prescriptions of > or =120
      tablets/year were defined as long-term users. A survey of a subgroup of patients
      without verified indication was performed. RESULTS: In all, 901 (2.1%) patients
      were long-term treated. Verified indications for treatment were identified for
      247/901 (27%). An upper GI endoscopy had been performed in 418 patients (46%). Of
      the 194/654 without verified indication who participated in the survey, 71%
      reported heartburn/acid regurgitation as the reason for therapy. On-demand
      therapy was reported by 43/194 (22%) and previous attempts to withdraw by 119/194
      (61%). CONCLUSIONS: The prevalence of PPI long-term treatment among primary care
      patients is 2.1%. The main reason for treatment is reflux symptoms or verified
      GERD. Rationalization of use of PPIs is possible as daily treatment without
      attempts to discontinue is frequently observed.

PMID- 19604181
TI  - Clinical trial: music reduces anxiety levels in patients attending for endoscopy.
AB  - BACKGROUND: Patients attending for endoscopy are generally anxious and worried.
      AIMS: To examine whether music reduced anxiety levels in patients attending for
      endoscopic procedures. METHODS: Prospective randomized controlled trial of 180
      patients (M:F 81:99). The effect of age (< or = or >51 years) and procedure
      (gastroscopy or flexible sigmoidoscopy/colonoscopy) on anxiety levels (state
      trait anxiety inventory) on arrival in the unit and immediately before the
      endoscopy procedure, after listening to music or no music (control group) for the
      same period. RESULTS: At baseline, anxiety levels were not influenced by age (<
      or =51 years, n = 56:42.21 +/- 9.18; >51 years, n = 124:39.99 +/- 10.13 (P =
      0.15) or procedure: gastroscopy, n = 87:39.43 +/- 9.9, flexible
      sigmoidoscopy/colonoscopy: n = 93:41.86 +/- 9.75 (P = 0.98). No difference was
      found in anxiety scores in the control group (n = 88) at baseline and immediately
      pre-endoscopy (P = 0.243), but music led to a significant reduction in anxiety
      scores (n = 92), which was maintained for all age groups irrespective of
      procedure (all P < 0.0001). CONCLUSIONS: Anxiety levels in patients attending for
      endoscopy were not influenced by age or procedure, but were significantly reduced
      by listening to music compared to controls. The availability of music within the
      endoscopy unit is a simple strategy that will improve the well-being of patients.

PMID- 19604183
TI  - Improving organ donation rates in the United Kingdom.

PMID- 19604184
TI  - Impact of a Bereavement and Donation Service incorporating mandatory 'required
      referral' on organ donation rates: a model for the implementation of the Organ
      Donation Taskforce's recommendations.
AB  - In 2008 the Organ Donation Taskforce published its recommendations for increasing
      organ donation in the UK by 50% over 5 years. Bolton NHS Trust has addressed the
      problem of low rates of organ donation by amalgamating Bereavement and Donation
      Services and introducing a trigger to refer automatically all potential organ
      donors to the regional transplant donor co-ordinators. We audited the ability of
      the new service to deliver the aims and recommendations of the Organ Donation
      Taskforce. Following the changes in service provision the number of tissue donors
      rose from six in 2002 to 246 in 2007. In the same period solid organ donation
      rates remained unchanged. The introduction of an automatic trigger for referral
      of potential donors in 2007 resulted in 31 referrals and 11 successful multi
      organ donors. The current service exceeds the aims of the Taskforce and offers
      the potential to meet UK organ donation targets without resorting to an 'opt out'
      system of presumed consent.

PMID- 19604185
TI  - Litigation related to inadequate anaesthesia: an analysis of claims against the
      NHS in England 1995-2007.
AB  - Inadequate anaesthesia may cause distress to the patient and lead to medical
      litigation. All claims made to the NHS Litigation Authority 1995-2007 were
      obtained and the data was examined independently by all authors and classified.
      In a dataset of 1067 claims there were 161 cases of inadequate anaesthesia and
      data were suitable for analysis in 159: intra-operative awareness (79), brief
      awake paralysis (20) and inadequate regional anaesthesia (60). The total cost of
      closed claims was pound 3.2 m. Cost was incurred in 100% of claims of brief awake
      paralysis, 87% of claims of awareness and 80% of claims of inadequate regional
      blockade. Mean cost of closed claims was pound 32,680 for anaesthetic awareness,
      pound 29,345 for inadequate regional blockade and pound 24,364 for brief awake
      paralysis. Inadequate anaesthesia accounts for 19% of anaesthesia-related claims
      in the NHS in England. Strategies that reduce anaesthetic awareness, drug errors
      and inadequate regional blockade are known and their improved implementation is
      likely to reduce such claims.

PMID- 19604186
TI  - Neurological complication analysis of 1000 ultrasound guided peripheral nerve
      blocks for elective orthopaedic surgery: a prospective study.
AB  - Little data exists regarding the frequency of neurological complications
      following ultrasound guided peripheral nerve blockade. Therefore, we studied
      single injection and continuous ultrasound guided interscalene, supraclavicular,
      infraclavicular, femoral and sciatic nerve blocks in patients undergoing
      orthopaedic extremity surgery. All patients were contacted during postoperative
      weeks 2-4 and questioned for numbness or altered sensation anywhere in the
      involved extremity, and pain or weakness unrelated to surgery. The presumed
      aetiology of symptoms was based on the collective agreement of principal
      investigator, primary surgeon and a neurologist. Multivariate analysis was
      performed for characteristics potentially important in the causation of
      neurological complications. Of 1010 consecutive blocks, successful follow up
      between weeks 2 and 4 occurred in 98.6%. New, all-cause, neurological symptoms
      were present in 56/690 blocks (8.2%) at day 10, 37/1010 (3.7%) at 1 month and
      6/1010 (0.6%) at 6 months. Most symptoms were due to causes unrelated to the
      block. Of 452 patients directly questioned at the time of the block, new
      neurological symptoms were more common in patients who experienced procedure
      induced paraesthesia (odds ratio = 1.7, p = 0.029). The postoperative
      neurological symptom rate in this series is very similar to those previously
      reported following traditional techniques.

PMID- 19604187
TI  - Monitor position and the accuracy and speed of ultrasound-guided nerve blocks.
AB  - Ultrasound is rapidly becoming an essential skill for all anaesthetists with an
      interest in regional anaesthesia. Using a single-blinded cross-over trial design,
      we assessed the accuracy and speed of simulated ultrasound-guided nerve blockade
      with the monitor either in direct line-of-sight or perpendicular to the line-of
      sight. Thirty-one anaesthetists participated in the study. Times taken to reach
      the targets were similar 18.4 (14.6) s with the monitor 'in-line' and 22.4 (26.7)
      s with the monitor perpendicular to the target. Needle placement was
      significantly more accurate when anaesthetists had the monitor in front of them
      (29 acceptable) than to the side (22 acceptable). For anaesthetists with limited
      ultrasound experience, the accuracy, but not speed, of ultrasound guided regional
      anaesthesia can be improved by aligning the monitor in the line of sight of the
      operator.

PMID- 19604188
TI  - Effects of different doses of remifentanil on the end-tidal concentration of
      sevoflurane required for tracheal intubation in children.
AB  - We investigated the effects of different doses of remifentanil on the end-tidal
      concentration of sevoflurane required for tracheal intubation in children without
      the use of neuromuscular blocking drugs. One hundred and thirty paediatric
      patients, aged 3-8 years, were randomly allocated to receive no remifentanil
      (group control) or remifentanil 0.1 microg kg(-1) min(-1) (group remi(0.1)), 0.2
      microg kg(-1) min(-1) (group remi(0.2)), 0.3 microg kg(-1) min(-1) (group
      remi(0.3)). All patients were anaesthetised using 5% sevoflurane. After loss of
      eyelash reflex, remifentanil 1 microg kg(-1) was injected over 1 min followed by
      an appropriate group-dependent infusion and the end-tidal sevoflurane
      concentration was changed. Predetermined end-tidal sevoflurane concentrations for
      each group were determined using the Dixon up-and-down method. After the target
      concentration of sevoflurane was maintained for 5 min, the child's trachea was
      intubated. Successful intubation was defined as excellent or good intubating
      conditions. The end-tidal concentration (SD) of sevoflurane for successful
      tracheal intubation in 50% of children (ED(50)) were 5.16 (0.22)% in control,
      3.27 (0.18)%, 1.81 (0.20)% and 1.01 (0.11)%, in remi(0.1), remi(0.2), and
      remi(0.3) groups, respectively. Using probit analysis, the 95% effective dose
      (ED(95)) of sevoflurane were 5.60% (95% CI 5.35-7.66), 3.77% (95% CI 3.45-7.74),
      2.18% (95% CI 1.96-3.86), 1.19% (95% CI 1.06-1.82) in control, remi(0.1),
      remi(0.2), and remi(0.3) groups, respectively.

PMID- 19604189
TI  - The effect of heart rate variability on request for labour epidural analgesia.
AB  - Maternal heart rate variability of 62 parturients were compared based on their
      choice of using (epidural group, 44 women) or not using (control, 18 women)
      epidural analgesia. Baseline heart rate variability and visual analogue scores
      were recorded when the cervix of the parturient dilated to 2-4 cm, and paired
      data were collected 1 h later. We found that parturients in the epidural group
      had greater heart rate variability at the beginning of labour. Multiple logistic
      regression analysis identified percentage of absolute difference in successive RR
      intervals exceeding 20 ms as the best indicator of choosing epidural analgesia.
      Almost all heart rate variability measures were unchanged 1 h later in both
      groups. We concluded that parturients who chose epidural analgesia had greater
      heart rate variability, and that percentage of absolute difference in successive
      RR intervals exceeding 20 ms could reflect their likelihood of requesting
      epidural analgesia at the beginning of labour.

PMID- 19604190
TI  - Previously undiagnosed aortic stenosis revealed by auscultation in the hip
      fracture population--echocardiographic findings, management and outcome.
AB  - The 2001 Report of the National Confidential Enquiry into Perioperative Deaths
      recommended that an echocardiogram should be performed on patients with aortic
      stenosis prior to anaesthesia. In this study we present the patient details,
      management and outcome of the 272 hip fracture patients with a previously
      undiagnosed murmur and echocardiographically proven aortic stenosis admitted from
      2001-2005 in our hospital. The patients with aortic stenosis were significantly
      older, and had significantly lower Abbreviated Mental Test Scores, than the
      control group of 3698 hip fracture patients without aortic stenosis. There were
      significant trends toward general anaesthesia over spinal anaesthesia, and use of
      invasive monitoring of blood pressure, as the severity of the aortic stenosis
      increased. There were no significant trends towards higher 30-day or 1-year
      mortality rates as the severity of the aortic stenosis increased. Resources for
      rapid pre-operative echocardiograms should be made available for hip fracture
      patients as the results have significant implications for their subsequent
      anaesthetic management.

PMID- 19604191
TI  - Peri-operative oral triiodothyronine replacement therapy to prevent postoperative
      low triiodothyronine state following valvular heart surgery.
AB  - This study evaluated the effect of oral triiodothyronine (T(3)) replacement
      therapy, starting on the day of the surgery, on thyroid hormone concentrations
      and clinical outcome in high-risk patients undergoing valvular heart surgery.
      Fifty patients were randomly allocated to either T(3) or placebo. In the
      treatment (T(3)) group patients received 20 microg of oral or nasogastric T(3)
      every 12 h starting just before induction of anaesthesia and until the first day
      after surgery. T(3) concentrations were significantly higher in the T(3) group
      than the placebo group from 1 to 36 h after removal of the aortic cross clamp.
      The number of patients requiring vasopressin after discontinuing cardiopulmonary
      bypass was significantly greater in the placebo group than the T(3) group.
      Significantly fewer patients required vasopressors in the T(3) group on the first
      day after surgery.

PMID- 19604192
TI  - Thyromental distance measurement--fingers don't rule.
AB  - Thyromental distance (TMD) measurement is commonly used to predict difficult
      intubation. We surveyed anaesthetists to determine how this test was being
      performed. Comparative accuracy of ruler measurement and other forms of
      measurement were also assessed in a meta-analysis of published literature. Of
      respondents, 72% used fingers for TMD measurement and also considered three
      finger widths the minimum acceptable TMD. In terms of distance, the minimum
      acceptable TMD was felt to be 6.5 cm by 55% of respondents. However, the actual
      width of three fingers was (range) 4.6-7.0 cm (mean 5.9 cm), with significant
      differences between genders and between proximal and distal interphalangeal
      joints. The meta-analysis showed ruler measurement increased test sensitivity
      (48% (95% CI 43-53) vs 16% (95% CI 14-19) without a ruler), when predicting
      difficult intubation.

PMID- 19604193
TI  - Cardiopulmonary exercise testing as a risk assessment method in non cardio
      pulmonary surgery: a systematic review.
AB  - This study reviews the predictive value of maximum oxygen consumption (VO2max)
      and anaerobic threshold, obtained through cardiopulmonary exercise testing, in
      calculating peri-operative morbidity and mortality in non-cardiopulmonary thoraco
      abdominal surgery. A literature review provided nine studies that investigated
      either one or both of these two variables across a wide range of surgical
      procedures. Six of the seven studies that reported sufficiently detailed results
      on peak oxygen consumption and four of the six studies that reported sufficiently
      detailed results on anaerobic threshold found them to be significant predictors.
      We conclude that peak oxygen consumption and possibly anaerobic threshold are
      valid predictors of peri-operative morbidity and mortality in non-cardiopulmonary
      thoraco-abdominal surgery. These indicators could potentially provide a means of
      allocating increased care to high-risk patients.

PMID- 19604194
TI  - The impact of manual in-line stabilisation on ventilation and visualisation of
      the glottis with the LMA CTrach: a randomised crossover trial.
AB  - The LMA CTrach (CTrach) enables ventilation, glottis visualisation and tracheal
      intubation via a laryngeal mask conduit. The CTrach has been successfully used in
      patients with cervical spine pathology, but it is unclear if cervical spine
      immobilisation affects its ease of use. In this randomised crossover trial, the
      CTrach was used once with and once without manual in-line stabilisation of the
      cervical spine in every patient. With manual in-line stabilisation, the median
      [IQR] time to achieve ventilation was 22 [16-32] s, compared with 19 [13-30] s
      without stabilisation (p = 0.065). With manual in-line stabilisation, the time to
      achieving a glottic views was 42 [30-63] s compared with 39 [25-53] s without
      stabilisation (p = 0.019). There was no difference in the success rates of
      achieving ventilation and glottic views. These results suggest that manual in
      line stabilisation does not affect use of the CTrach.

PMID- 19604195
TI  - An assessment of the efficiency of the Glostavent ventilator.
AB  - In parts of the world where supplies of oxygen and electricity are erratic,
      ventilating patients' lungs can be problematic. Should the electricity supply
      fail, gas driven ventilators have an advantage as they can continue functioning.
      However, many are extravagant in their requirement for the driving gas. The
      Glostavent ventilator was designed to minimise these requirements. We measured
      the duration of ventilation achieved by the Glostavent ventilator using an E-size
      oxygen cylinder at a range of minute volumes, and the inspired oxygen
      concentration achieved by recycling the driving gas. The period of mechanical
      ventilation from a single E-size cylinder ranged from 11 h 8 min (SD 4 min) with
      a minute volume of 7 l min(-1) to 18 h 15 min (SD 7 min) with a minute volume of
      3 l min(-1). The mean fractional inspired oxygen concentration achieved by
      recycling the driving gas without further inspired oxygen supplementation was
      0.33. We conclude that the Glostavent ventilator performs as efficiently and cost
      effectively as predicted.

PMID- 19604196
TI  - Recurrent torsades de pointes in association with a very low calorie diet.
AB  - The use of very low calorie diets under medical supervision is becoming
      increasingly popular in the UK, as the incidence of obesity continues to rise. We
      report the case of torsades de pointes developing during such a diet. Torsades de
      pointes has been reported in association with very low calorie diets in the past
      but to our knowledge, this is the first report since the introduction of newer,
      nutritionally complete versions of the diet. We review the intensive care
      management of recurrent torsades de pointes resistant to standard therapy and its
      relationship to dieting and obesity.

PMID- 19604197
TI  - Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis.
AB  - Accurate prediction of neurological outcome in survivors of cardiac arrest may be
      difficult. We report the case of a 44-year-old survivor of a hypoxic cardiac
      arrest who repeatedly developed relentless myoclonic jerks on attempted
      discontinuation of his propofol infusion. These were initially thought to
      represent myoclonic status epilepticus before the correct diagnosis of Lance
      Adams syndrome was made. Lance-Adams syndrome is a rare disorder seen in
      survivors of profound hypoxic episodes. It is characterised by intention
      myoclonus but preserved intellect. Accurate distinction between myoclonic status
      epilepticus and Lance-Adams syndrome is vital as they have very different
      prognoses. The different pathophysiology and distinguishing clinical features of
      these two conditions are highlighted.

PMID- 19604198
TI  - Use of the McGrath video laryngoscope in awake patients.
AB  - Reported are three cases of successful tracheal intubation using the McGrath
      Video Laryngoscope in awake patients. All three patients had predicted difficult
      direct laryngoscopy and signs of upper airway obstruction.

PMID- 19604200
TI  - Effect of the 48-hour week on training in anaesthesia.

PMID- 19604201
TI  - Modernising Medical Careers: impact on training in a district general hospital.

PMID- 19604203
TI  - Methicillin-resistant Staphylococcus aureus and high bed occupancy.

PMID- 19604204
TI  - Bougie trauma: insertion or railroad?

PMID- 19604206
TI  - The problem of cross-over design in airway studies.

PMID- 19604207
TI  - Thrombelastometer and low molecular weight heparin.

PMID- 19604208
TI  - The Pentax-AWS for airway obstruction after tracheal extubation.

PMID- 19604209
TI  - Peri-operative warming in Caesarean sections.

PMID- 19604211
TI  - Postoperative residual curarisation--facts and fictions.

PMID- 19604212
TI  - AAGBI guidelines on the use of neuromuscular blockade monitoring.

PMID- 19604213
TI  - Small doses of methylene blue, previously considered safe, can precipitate
      serotonin toxicity.

PMID- 19604225
TI  - Genomic convergence of genome-wide investigations for complex traits.
AB  - Genome-wide investigations for identifying the genes for complex traits are
      considered to be agnostic in terms of prior assumptions for the responsible DNA
      alterations. The agreement of genome-wide association studies (GWAS) and genome
      wide linkage scans (GWLS) has not been explored to date. In this study, a genomic
      convergence approach of GWAS and GWLS was implemented for the first time in order
      to identify genomic loci supported by both methods. A database with 376 GWLS and
      102 GWAS for 19 complex traits was created. Data regarding the location and
      statistical significance for each genetic marker were extracted from articles or
      web-based databases. Convergence was quantified as the proportion of significant
      GWAS markers located within linked regions. Convergence was variable (0-73.3%)
      and was found to be significantly higher than expected by chance only for two of
      the 19 phenotypes. Seventy five loci of interest were identified, which being
      supported by independent lines of evidence, could merit prioritization in future
      investigations. Although convergence is supportive of genuine effects, lack of
      agreement between GWLS and GWAS is also indicative that these studies are
      designed to answer different questions and are not equally well suited for
      deciphering the genetics of complex traits.

PMID- 19604226
TI  - PedStr software for cutting large pedigrees for haplotyping, IBD computation and
      multipoint linkage analysis.
AB  - We propose an automatic heuristic algorithm for splitting large pedigrees into
      fragments of no more than a user-specified bit size. The algorithm specifically
      aims to split large pedigrees where many close relatives are genotyped and to
      produce a set of sub-pedigrees for haplotype reconstruction, IBD computation or
      multipoint linkage analysis with the help of the Lander-Green-Kruglyak algorithm.
      We demonstrate that a set of overlapping pedigree fragments constructed with the
      help of our algorithm allows fast and effective haplotype reconstruction and
      detection of an allele's parental origin. Moreover, we compared pedigree
      fragments constructed with the help of our algorithm and existing programs PedCut
      and Jenti for multipoint linkage analysis. Our algorithm demonstrated
      significantly higher linkage power than the algorithm of Jenti and significantly
      shorter running time than the algorithm of PedCut. The software package PedStr
      implementing our algorithms is available at
      http://mga.bionet.nsc.ru/soft/index.html.

PMID- 19604227
TI  - A new pulsatile volumetric device with biomorphic valves for the in vitro study
      of the cardiovascular system.
AB  - A pulsatile mock loop system was designed and tested. This prototype represents a
      versatile, adjustable, and controllable experimental apparatus for in vitro
      studies of devices meant to interface with the human circulatory system. The
      pumping system consisted of a ventricular chamber featuring two biomorphic
      silicone valves as the inlet and outlet valves. The chamber volume is forced by a
      piston pump moved by a computer-controlled, low-inertia motor. Fluid dynamic
      tests with the device were performed to simulate physiological conditions in
      terms of cardiac output (mean flow of 5 and 6 L/min, with beat rates from 60 to
      80 bpm), of rheological properties of the processed fluid, and of systemic
      circulation impedance. The pulsating actuator performed a good replication of the
      physiological ventricular behavior and was able to guarantee easy control of the
      waveform parameters. Experimental pressure and flow tracings reliably simulated
      the physiological profiles, and no hemolytic subatmospheric pressures were
      revealed. The performance of the prototype valves was also studied in terms of
      dynamic and static backflow, effective orifice area, and pressure loss, resulting
      in their applicability for this device. Mechanical reliability was also tested
      over 8 h. The device proved to be a reliable lab apparatus for in vitro tests;
      the pumping system also represents a first step toward a possible future
      application of pulsating perfusion in the clinic arena, such as in short-term
      cardiac assist and pulsatile cardiopulmonary bypass.

PMID- 19604228
TI  - Development of an algorithm to regulate pump output for a closed air-loop type
      pneumatic biventricular assist device.
AB  - The closed air space-type of extracorporeal pneumatic ventricular assist device
      (VAD) developed by the Korea Artificial Organ Center utilizes a bellows
      transforming mechanism to generate the air pressure required to pump blood. This
      operating mechanism can reduce the size and weight of the driving unit; however,
      the output of the blood pump can be affected by the pressure loading conditions
      of the blood sac. Therefore, to guarantee a proper pump output level, regardless
      of the pressure loading conditions that vary over time, automatic pump output
      regulation of the blood pump is required. We describe herein a pump output
      regulation algorithm that was developed to maintain pump output around a
      reference level against various afterload pressures, and verified the pump
      performance in vitro. Based on actual operating conditions in animal experiments,
      the pumping rate was limited to 40-84 beats per minute, and the afterload
      pressure was limited to 80-150 mm Hg. The tested reference pump output was 4.0
      L/min. During experiments, the pump output was successfully and automatically
      regulated within the preset area regardless of the varying afterload conditions.
      The results of this preliminary experiment can be used as the basis for an
      automatic control algorithm that can enhance the stability and reliability of the
      applied VAD.

PMID- 19604229
TI  - An animal study of a newly developed skin-penetrating pad and covering material
      for catheters to prevent exit-site infection in continuous ambulatory peritoneal
      dialysis.
AB  - Because currently available peritoneal dialysis catheters are not sufficiently
      biocompatible with the skin and subcutaneous tissue at the site of penetration,
      exit-site infection due to pericatheter pocket formation caused by epidermal
      downgrowth over a long period of time has increasingly become a problem. We
      developed a new, biocompatible, segmented polyurethane porous material and
      devised a novel skin-penetrating pad, the form and material of which we optimized
      for application in peritoneal dialysis catheters. For the extent of tissue
      ingrowth into this porous material to be examined, test materials with different
      pore diameters were inserted into hollow silicone tubes and implanted in the
      subcutaneous tissue of a goat. Four weeks later, the tubes were extracted, and,
      after the extent of granulation tissue ingrowth was measured, histopathological
      evaluation was made. Our novel skin-penetrating pad has three disklike layers of
      the segmented polyurethane material with different pore sizes, into the center of
      which a polyurethane catheter is inserted. These pads were implanted in the skin
      of a goat and clinically observed over a 2-year period, after which they were
      extracted and histopathologically analyzed. In accordance with actual clinical
      procedures, a commercial CAPD catheter equipped with our skin-penetrating pad was
      left indwelling in a goat for 4 months, and the performance of the pad was
      evaluated after repeated periodic infusion and drainage of the dialysate in and
      out of the abdominal cavity. There was no inflammation of the ingrown tissue in
      the pores of the segmented polyurethane material as well as the surrounding
      tissue, which indicated favorable tissue biocompatibility. The extent of tissue
      ingrowth was greater as the pore size of the material was larger, and the tissue
      tended to be mature, mainly consisting of collagenous fibers. The skin
      penetrating pad using the porous material, of which tissue ingrowth was thus
      optimized, tightly adhered to the goat skin throughout the 2-year experimental
      period without any special wound care such as cleansing or disinfection. The
      performance of the skin-penetrating pad was similarly favorable when attached to
      a commercial continuous ambulatory peritoneal dialysis catheter. The newly
      developed segmented polyurethane porous material had excellent tissue
      biocompatibility and tissue ingrowth. The skin-penetrating pad devised by using
      this porous material did not cause epidermal downgrowth, suggesting that it may
      be effective for the prevention of exit-site infection.

PMID- 19604230
TI  - CD4/CD8 T-cell ratio in peritoneal dialysis effluents predicts the outcome of
      peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.
AB  - This study aimed to clarify the role of peritoneal T-lymphocytes in peritoneal
      immune defense mechanisms. This study was designed to examine the changes in T
      cell subpopulations during peritonitis in patients treated with continuous
      ambulatory peritoneal dialysis (CAPD). Our observations were correlated to
      responses to treatment and with outcomes. The present study was carried out in 20
      patients (8 males, 12 females) under CAPD. Peritonitis was diagnosed according to
      the criteria defined by the Ad Hoc Advisory Committee on Peritonitis Management.
      Peritoneal dialysate effluent (PDE) samples were collected from our patients, and
      lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16+56+, CD4/CD8 ratio)
      were quantitated by using monoclonal antibodies. CD4/CD8 ratio was measured every
      day during peritonitis until the patients had completely recovered. The serial
      measurements of the CD4/CD8 ratio made in the PDE during peritonitis followed two
      patterns: the first pattern was characterized by a progressive increase in the
      CD4/CD8 ratio. The CD4/CD8 ratios on days 5, 6, and 7 were significantly higher
      than those on day 1 (P < 0.05). Overall, the patients who exhibited pattern 1 had
      favorable clinical courses. The second pattern was characterized by high initial
      CD4/CD8 ratios, which progressively decreased significantly (P < 0.05). This
      second pattern was associated with a delayed clinical response to treatment.
      Symptoms and signs of peritonitis persisted beyond 72 h. The pattern of the
      CD4/CD8 ratio in PDE may determine the outcome of peritonitis in CAPD patients.

PMID- 19604231
TI  - Are the new oral anticoagulant agents easy to use? Report from an orthopaedic
      ward.

PMID- 19604232
TI  - Genetic variants of coagulation factor XIII and the risk of myocardial infarction
      in young women.

PMID- 19604234
TI  - Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal
      type.
AB  - Extranodal natural killer (NK)/T-cell lymphoma, nasal type, has a unique
      geographic distribution. Its pathology is characterized by marked angio-invasion
      and tissue necrosis. A typical NK-cell phenotype is usually present: CD2(+), CD3
      epsilon+, CD56(+), cytotoxic molecules+ and Epstein-Barr virus (EBV)+. Magnetic
      Resonance Imaging helps to clearly define the local involvement. Positron
      Emission Tomography helps to demonstrate system spread. Various prognostic
      variables (International Prognostic Index or the Korean Prognostic Index) should
      be documented. This may include quantification of plasma EBV DNA. For localized
      nasal disease, radiotherapy is important, although chemotherapy is often added.
      Sustainable remission is observed in over half of these patients. For extra-nasal
      or disseminated disease, systemic chemotherapy becomes the mainstay and the
      prognosis is usually poor. Doxorubicin-containing regimens are not entirely
      satisfactory and L-asparaginase containing regimens are being investigated.
      Patients with poor prognostic features may be considered for an early autologous
      haematopoietic stem cell transplant. Allogeneic transplantation is efficacious
      but is associated with high transplant-related mortality.

PMID- 19604233
TI  - Postpolycythaemic myelofibrosis: frequency and risk factors for this complication
      in 116 patients.
AB  - Postpolycythaemic myelofibrosis (PPMF) is a known complication of polycythaemia
      vera (PV) but information regarding its incidence and predisposing factors is not
      well defined. In 116 subjects consecutively diagnosed with PV in a single
      institution (median age 62 years, range: 20-88), the probability of PPMF was
      analysed by the Kaplan-Meier method, followed by the log-rank test. With a mean
      follow-up of 8 years (95% confidence interval: 6.6-9), 17 patients had evolved
      into PPMF (15%). The probability of evolution to PPMF was 16% at 10 years and 34%
      at 15 years. Age, gender, spleen size, leucocytosis, thrombocytosis or
      cytoreductive treatment were not associated with an increased risk of PPMF. The
      actuarial probability of PPMF at 15 years was higher in those patients presenting
      at diagnosis with endogenous megakaryocytic colony formation (59% when present
      versus 10% when absent, P = 0.03), an elevated serum lactate dehydrogenase (LDH)
      level (69% vs. 23% in patients with normal LDH, P = 0.04), and in those who were
      heterozygous for the JAK2 V617F mutation (55% vs. 17% in heterozygotes, P =
      0.04). In conclusion, PPMF is a frequent complication in PV patients at 15 years
      with the risk being higher in patients with increased LDH, endogenous
      megakaryocytic colony formation or a high JAK2 V617F allele burden.

PMID- 19604235
TI  - The anti-histaminic cyproheptadine synergizes the antineoplastic activity of
      bortezomib in mantle cell lymphoma through its effects as a histone deacetylase
      inhibitor.
AB  - Cyproheptadine, an inhibitor of the H1 histamine receptors, has recently shown
      activity in models of leukaemia and myeloma, presumably through inhibition of
      cyclin-D expression. Mantle cell lymphoma (MCL) is an aggressive subtype of non
      Hodgkin lymphoma characterized by overexpression of cyclin-D1. We investigated
      the effect of cyproheptadine alone and in combination with the proteasome
      inhibitor bortezomib in models of MCL. The combination of these drugs was
      mathematically synergistic, producing significant reductions in the mitochondrial
      membrane potential leading to apoptosis. In a severe combined immunodeficient
      beige mouse model, cyproheptadine plus bortezomib demonstrated a statistically
      significant advantage compared to either agent alone.

PMID- 19604236
TI  - A new genetic lesion in B-CLL: a NOTCH1 PEST domain mutation.

PMID- 19604238
TI  - Altered mRNA expression of PAX5 is a common event in acute lymphoblastic
      leukaemia.

PMID- 19604237
TI  - Pretreatment angiogenic cytokines predict response to chemoimmunotherapy in
      patients with chronic lymphocytic leukaemia.
AB  - Serum levels of pro-[vascular endothelial growth factor (VEGF)] and anti
      [thrombospondin-1 (TSP)] angiogenic cytokines were prospectively measured in a
      phase II trial of chemoimmunotherapy (CIT) for chronic lymphocytic leukaemia
      (CLL) patients (n = 56). Pretreatment VEGF levels were lower among patients who
      achieved complete remission (CR) or nodular partial remission (nPR) relative to
      those with partial remission (PR) or stable/progressive disease (median 122.0
      pg/ml vs. 246.8 pg/ml; P = 0.03). VEGF:TSP ratio was lower (anti-angiogenic
      phenotype) among patients who achieved CR/nPR. The pretreatment VEGF:TSP ratio
      also correlated with overall survival (P = 0.008). A pro-angiogenic profile
      appears associated with diminished response and inferior survival in CLL patients
      receiving CIT.

PMID- 19604239
TI  - Levels of non-transferrin-bound iron as an index of iron overload in patients
      with thalassaemia intermedia.
AB  - Non-transferrin-bound iron (NTBI) was evaluated as an index of iron overload in a
      cross-sectional randomised study in 74 non-transfused patients with thalassaemia
      intermedia (TI). Mean NTBI (2.92 +/- 3.43 micromol/l), serum ferritin (1023 +/-
      780 ng/ml) and liver iron concentration (LIC; 9.0 +/- 7.4 mg Fe/g dry weight)
      were increased above reference-range levels. Significant positive correlations
      occurred between mean NTBI and LIC (Pearson correlation 0.36; P = 0.002) and
      serum ferritin (Pearson correlation 0.421; P < 0.0001); with higher levels
      observed in splenectomised patients. NTBI assessment has potential as a simple
      reliable approach to determining iron status in TI.

PMID- 19604240
TI  - Identification of new target molecules PTK2, TGFBR2 and CD9 overexpressed during
      advanced bone marrow remodelling in primary myelofibrosis.
AB  - Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by
      remodelling of the bone marrow, including progressive myelofibrosis and
      exaggerated angiogenesis. Advanced PMF frequently shows a full-blown fibre
      meshwork, which avoids aspiration of cells, and the expression profile of genes
      related to stroma pathology at this stage remains largely undetermined. We
      investigated bone marrow core biopsies in PMF showing various degrees of
      myelofibrosis by custom-made low density arrays (LDA) representing target genes
      with designated roles in synthesis of extracellular matrix, matrix remodelling,
      cellular adhesion and motility. Among a set of 11 genes up-regulated in advanced
      stages of PMF (P < or = 0.01) three candidates, PTK2 protein tyrosine kinase 2
      (PTK2), transforming growth factor beta type II receptor (TGFBR2) and motility
      related protein-1 (CD9 molecule, CD9), were investigated in more detail. PTK2,
      TGFBR2 and CD9 were significantly overexpressed in larger series of advanced PMF
      stages (P < or = 0.01 respectively). Endothelial cells of the increased
      microvessel network in PMF could be identified as a predominant source for PTK2,
      TGFBR2 and CD9. CD9 also strongly identified activated fibroblasts in advanced
      myelofibrosis. We conclude that PTK2, TGFBR2 and CD9 represent new target
      molecules involved in bone marrow remodelling of PMF and warrant further
      investigation for potential targeted therapy.

PMID- 19604242
TI  - Fatal histiocytic proliferative disorders in paediatric HIV infection with
      cytomegalovirus end-organ disease.

PMID- 19604243
TI  - Allogeneic stem cell transplantation for patients with refractory anaemia with
      matched related and unrelated donors: delay of the transplant is associated with
      inferior survival.
AB  - Allogeneic stem cell transplantation (alloSCT) for patients with refractory
      anaemia may result in a 50% event-free survival, but the high non-relapse
      mortality (NRM) precludes a general application of this therapeutic modality.
      This study evaluated the impact of various pre-transplant variables, including
      disease duration, intensity of the conditioning regimen, type of donor and year
      of transplantation on outcome. The study population consisted of 374 patients;
      244 were transplanted from human leucocyte antigen (HLA)-identical siblings and
      130 patients from matched unrelated donors. The median age was 39 years. One
      hundred and two patients were transplanted after reduced intensity conditioning
      (RIC). The overall 4-year survival was 52%. The 4-year survival of patients
      transplanted with HLA-identical sibling donors and matched unrelated donors was
      52% and 50%, respectively. Multivariate analysis showed an improved survival (P =
      0.05) and a lower NRM (P = 0.02) when the transplantation was performed in recent
      years. Increasing age, and disease duration of >12 months were associated with
      inferior survival. RIC resulted in a similar survival despite an increased
      relapse risk (P = 0.02). This improved outcome permits alloSCT in patients older
      than 50 years of age, even with the use of matched unrelated donors. AlloSCT
      should be preferentially performed early after diagnosis after careful analysis
      of prognostic variables.

PMID- 19604241
TI  - Differences in the prevalence of growth, endocrine and vitamin D abnormalities
      among the various thalassaemia syndromes in North America.
AB  - This study aimed to determine differences in the rates of growth, endocrine- and
      calcium-related abnormalities in the various thalassemia syndromes in North
      America treated with current therapies. Medical history, physical examinations
      and blood and urine collections were obtained from patients with all thalassemia
      syndromes age 6 years and older in the Thalassemia Clinical Research Network. 361
      subjects, 49% male, mean age 23.2 years (range 6.1-75 years) were studied.
      Approximately 25% of children and adults, regardless of the thalassemia syndrome,
      had short stature. Overall growth in children was mildly affected. Final height
      was close to midparental height (z = -0.73 +/- 1.24). Patients with beta
      thalassemia major (TM) had higher rates of hypogonadism, multiple
      endocrinopathies, worse hyperglycaemia, subclinical hypoparathyroidism and
      hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was
      frequently under-treated. 12.8% of the subjects had 25 vitamin D concentrations
      less than 27 nmol/l and 82% less than 75 nmol/l, regardless of the thalassemia
      syndrome. Adolescents had lower 25 vitamin D levels than children and adults.
      Compared to patients with other thalassemia syndromes, those with beta TM
      suffered from higher rates of multiple endocrinopathies, abnormal calcium
      metabolism and hypercalciuria. Vitamin D abnormalities were high among
      adolescents.

PMID- 19604244
TI  - Intraperitoneal administration of paclitaxel solubilized with poly(2
      methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) for peritoneal
      dissemination of gastric cancer.
AB  - Intraperitoneal (i.p.) administration of paclitaxel (PTX) is a hopeful
      therapeutic strategy for peritoneal malignancy. Intravenously (i.v.) injected
      nanoparticle anticancer drugs are known to be retained in the blood stream for a
      long time and favorably extravasated from vessels into the interstitium of tumor
      tissue. In this study, we evaluated the effect of i.p. injection of PTX (PTX
      30W), which was prepared by solubulization with water-soluble amphiphilic polymer
      composed of PMB-30W, a co-polymer of 2-methacryloxyethyl phosphorylcholine and n
      butyl methacrylate, for peritoneal dissemination of gastric cancer. In a
      peritoneal metastasis model with transfer of MKN45P in nude mice, the effect of
      i.p. administration of PTX-30W was compared with conventional PTX dissolved in
      Cremophor EL (PTX-Cre). The drug accumulation in peritoneal nodules was evaluated
      with intratumor PTX concentration and fluorescence microscopic observation. PTX
      30W reduced the number of metastatic nodules and tumor volume significantly more
      than did conventional PTX dissolved in Cremophor EL (PTX-Cre), and prolonged the
      survival time (P < 0.05). PTX concentration in disseminated tumors measured by
      HPLC was higher in the PTX-30W than in the PTX-Cre group up to 24 h after i.p.
      injection. Oregon green-conjugated PTX-30W, i.p. administered, preferentially
      accumulated in relatively hypovascular areas in the peripheral part of
      disseminated nodules, which was significantly greater than the accumulation of
      PTX-Cre. I.p. administration of PTX-30W may be a promising strategy for
      peritoneal dissemination, due to its superior characteristics to accumulate in
      peritoneal lesions.

PMID- 19604245
TI  - Tumor histology in lymph vessels and lymph nodes for the accurate prediction of
      outcome among breast cancer patients treated with neoadjuvant chemotherapy.
AB  - The present study investigated fibrotic foci (FFs), the grading system for lymph
      vessel tumor emboli (LVTEs), and the histological characteristics of nodal
      metastatic tumors that were significantly associated with the outcomes of 115
      patients with invasive ductal carcinoma (IDC) who had received neoadjuvant
      chemotherapy. We compared the outcome predictive power of FFs, the grading system
      for LVTEs, and the histological characteristics of metastatic tumors in lymph
      nodes with the well-known clinicopathological characteristics of tumor recurrence
      and tumor-related death in multivariate analyses. The presence of FFs, as
      assessed by a biopsy performed before neoadjuvant chemotherapy, significantly
      increased the hazard rates (HRs) for tumor-related death in all the cases and in
      cases with nodal metastasis. The grading system for LVTEs, which was assessed
      using surgical specimens obtained after neoadjuvant chemotherapy, was
      significantly associated with increasing hazard rates (HRs) for tumor recurrence
      and tumor-related death in all the cases and in cases with nodal metastasis.
      Moderate to severe stroma in nodal metastatic tumors and five or more mitotic
      figures in nodal metastatic tumors were significantly associated with elevated
      HRs for tumor recurrence and tumor-related death among all the cases. These
      results indicated that FFs, the grading system for LVTEs, and the histological
      characteristics of tumor cells in lymph nodes play important roles in predicting
      the tumor progression of IDCs of the breast in patients treated with neoadjuvant
      chemotherapy.

PMID- 19604246
TI  - Phase I clinical study of a peptide vaccination for hepatitis C virus-infected
      patients with different human leukocyte antigen-class I-A alleles.
AB  - Hepatitis C virus (HCV) infection has a high risk of liver cirrhosis and
      hepatocellular carcinoma at later stages. We recently identified a peptide
      derived from the HCV core protein capable of inducing both cellular and humoral
      responses to nearly all HCV-positive patients in Japan with different human
      leukocyte antigen (HLA)-class I-A alleles. To assess the safety and immune
      responses to this novel peptide, we conducted a phase I dose-escalation study of
      the vaccination for 26 HCV-positive patients who were either non-responders to
      the interferon-based therapy (n = 23) or refused it (n = 3). The regimen was well
      tolerated, with no severe vaccine-related toxicity. Twenty-five and 22 patients
      completed the first and second cycle vaccination (6 and 12 vaccine injections),
      respectively. After a series of six vaccine injections, peptide-specific CTL
      activity was augmented in peripheral blood mononuclear cells from 15 of 25
      patient samples, with an expected optimal dose of 1 mg peptide. After 12 vaccine
      injections, peptide-specific IgG production was augmented in plasma from the
      majority of patients (15 of 22 patients) tested, but not in a dose-dependent
      fashion. There were two HCV RNA responders with >1 log declines. Among patients
      whose pre-vaccination levels of alanine aminotransferase and alpha feto-protein
      exceeded the normal ranges, a <30% decrease was found in 7 of 24 and three of six
      patients, respectively. Because of its tolerability and higher rate of immune
      boosting, this protocol is recommended for a phase II study to investigate its
      clinical efficacy.

PMID- 19604247
TI  - Up-regulation of integrin beta3 in radioresistant pancreatic cancer impairs
      adenovirus-mediated gene therapy.
AB  - Adenovirus-mediated gene therapy is a promising approach for the treatment of
      pancreatic cancer. We previously reported that radiation enhanced adenovirus
      mediated gene expression in pancreatic cancer, suggesting that adenoviral gene
      therapy might be more effective in radioresistant pancreatic cancer cells. In the
      present study, we compared the transduction efficiency of adenovirus-delivered
      genes in radiosensitive and radioresistant cells, and investigated the underlying
      mechanisms. We used an adenovirus expressing the hepatocyte growth factor
      antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two
      radioresistant human pancreatic cancer cell lines using fractionated irradiation.
      Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad
      NK4, and NK4 levels in the cells were measured. In order to investigate the
      mechanisms responsible for the differences in the transduction efficiency between
      these cells, we measured expression of the genes mediating adenovirus infection
      and endocytosis. The results revealed that NK4 levels in radioresistant cells
      were significantly lower (P < 0.01) than those in radiosensitive cells, although
      there were no significant differences in adenovirus uptake between radiosensitive
      cells and radioresistant cells. Integrin beta3 was up-regulated and the Coxsackie
      virus and adenovirus receptor was down-regulated in radioresistant cells, and
      inhibition of integrin beta3 promoted adenovirus gene transfer. These results
      suggest that inhibition of integrin beta3 in radioresistant pancreatic cancer
      cells could enhance adenovirus-mediated gene therapy.

PMID- 19604248
TI  - Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist.
AB  - Ticagrelor (AZD6140) is the first reversibly binding oral P2Y(12) receptor
      antagonist that blocks ADP-induced platelet aggregation. Unlike thienopyridines,
      which irreversibly bind to the P2Y(12) receptor for the lifetime of the platelet,
      ticagrelor binds reversibly to the receptor and exhibits rapid onset and offset
      of effect, which closely follow drug exposure levels. Animal models indicate
      greater separation between antithrombotic effects and bleeding effects with
      ticagrelor than with thienopyridines. Unlike the thienopyridines, ticagrelor does
      not require metabolic activation. It is quickly absorbed and exhibits a rapid
      antiplatelet effect, with higher and more consistent levels of inhibition of
      platelet aggregation (IPA) being maintained across the dosing interval than with
      clopidogrel. IPA levels decline with plasma drug levels after discontinuation of
      dosing. In the phase II DISPERSE-2 trial of 990 patients with non-ST-elevation
      acute coronary syndromes (ACS), ticagrelor treatment with 90 mg and 180 mg twice
      daily showed comparable rates of major and minor bleeding compared with
      clopidogrel 75 mg while there were numerically fewer myocardial infarctions.
      Ticagrelor resulted in greater IPA in clopidogrel-naive patients and produced
      substantial additional reductions in platelet aggregation activity in patients
      pretreated with clopidogrel. Ticagrelor treatment was well tolerated in DISPERSE
      2, and discontinuation rates were comparable to those observed for clopidogrel.
      An increased risk of mild to moderate dyspnea and mostly asymptomatic ventricular
      pauses were observed in phase II studies. The mechanisms for these effects are
      currently being investigated. The efficacy and safety of ticagrelor are being
      further evaluated in the phase III PLATO trial, involving approximately 18,000
      patients with ACS, including both ST-elevation and non-ST-elevation ACS.

PMID- 19604249
TI  - Valsartan improves endothelial dysfunction in hypertension: a randomized, double
      blind study.
AB  - Endothelial dysfunction can predict cardiac outcomes in hypertension and
      reversing this abnormality has become an attractive therapeutic objective. We
      tested the hypothesis that blocking the angiotensin type 1 (AT(1)) receptor with
      valsartan in comparison with amlodipine would lead to an improvement in forearm
      resistance artery endothelial dysfunction. In total, 25 hypertensive subjects
      (mean age 60 years, SD 8) with a mean daytime ambulatory blood pressure (BP) of
      154 (10)/97 (6) mmHg were randomized following a 3-week placebo run-in period to
      a double-blind, crossover trial of 16-week treatment periods with either
      valsartan or amlodipine, separated by a 3-week washout period. Intra-arterial
      infusions of acetylcholine (ACh) and N(G)-monomethyl-L-arginine (L-NMMA) were
      used to assess stimulated and basal endothelium-dependent nitric oxide (NO)
      release, respectively. Coinfusion of ACh and L-NMMA was employed to investigate
      the existence of an NO-independent vasodilatory pathway. Valsartan and amlodipine
      each lowered the clinical BP to the same extent (139 [7]/87 [6] and 139 [11]/89
      [4] mmHg, respectively). The vasodilatory response to ACh was significantly
      increased with valsartan (maximal percentage change in forearm blood flow (max.
      DeltaFBF%) 301 [47] vs. 185 [34], mean [SEM]; P < 0.05) as compared with placebo,
      but remained unchanged with amlodipine. Both valsartan and amlodipine similarly
      increased the vasoconstrictive response to L-NMMA (max. DeltaFBF%-43 [5], -42
      [5], respectively, vs. -26 [3] baseline; P < 0.001). The vasodilatory response
      after coinfusion of ACh and L-NMMA was significantly (P < 0.05) enhanced only
      with valsartan. Valsartan reserved peripheral endothelial dysfunction through
      both NO-dependent and -independent pathways, while for the same degree of BP
      control, amlodipine had only a partial effect on NO bioactivity.

PMID- 19604253
TI  - Comment on Rubino et al., 'Association of the C677T polymorphism in the MTHFR
      gene with migraine: a meta-analysis'.

PMID- 19604254
TI  - Migraine and the hypothalamus.
AB  - Migraine is a complex brain disorder where several neuronal pathways and
      neurotransmitters are involved in the pathophysiology. To search for a specific
      anatomical or physiological defect in migraine may be futile, but the
      hypothalamus, with its widespread connections with other parts of the central
      nervous system and its paramount control of the hypophysis and the autonomic
      nervous system, is a suspected locus in quo. Several lines of evidence support
      involvement of this small brain structure in migraine. However, whether it plays
      a major or minor role is unclear. The most convincing support for a pivotal role
      so far is the activation of the hypothalamus shown by positron emission
      tomography (PET) scanning during spontaneous migraine attacks. A well-known
      theory is that the joint effect of several triggers may cause temporary
      hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had
      consistently confirmed hypothalamic activation prior to migraine headache, this
      hypothesis would have been supported. However, such evidence has not been
      provided, and the role of the hypothalamus in migraine remains puzzling. This
      review summarizes and discusses some of the clues.

PMID- 19604255
TI  - Translational Mini-Review Series on Vaccines for HIV: T lymphocyte trafficking
      and vaccine-elicited mucosal immunity.
AB  - Many pathogens use mucosal surfaces to enter and propagate within the host,
      making particularly desirable vaccines that target immune responses specifically
      to mucosal compartments. The majority of mucosal vaccine design strategies to
      date have been empirical in nature. However, an emerging body of basic
      immunological knowledge is providing new insights into the regulation of tissue
      specific lymphocyte trafficking and differentiation. These insights afford the
      opportunity for the rational design of vaccines that focus immune responses at
      mucosal surfaces. Mucosal cellular immunity may prove critical for protection in
      the context of HIV infection, and thus there has been considerable interest in
      developing vaccines that target HIV-specific cellular immune responses to the
      gastrointestinal and vaginal mucosa. However, the optimal strategies for
      eliciting mucosal cellular immune responses through vaccination remain to be
      determined. Here, we review both recent vaccine studies and emerging paradigms
      from the basic immunological literature that are relevant to the elicitation of
      potent and protective mucosal cellular immune memory. Increasing the synergy
      between these avenues of research may afford new opportunities for mucosal
      vaccine design.

PMID- 19604256
TI  - Translational Mini-Review Series on Vaccines for HIV: Harnessing innate immunity
      for HIV vaccine development.
AB  - Innate immunity is critical for shaping vaccine-elicited adaptive immune
      responses. Several classes of immune sensors, including Toll-like receptors,
      retinoic acid-inducible gene-I-like receptors, nucleotide-binding oligomerization
      domain-like receptors and cytosolic DNA receptors mediate important innate immune
      pathways and provide potential targets for novel adjuvant development.
      Understanding how innate immunity modulates adaptive immune responses will
      probably be important for optimizing vaccine candidates. Here, we review recent
      advances in innate immunity, focusing upon their potential applications in
      developing adjuvants and vectors for HIV vaccines.

PMID- 19604257
TI  - Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed
      therapy for autoimmune diseases.
AB  - B cells play an important role in the pathogenesis of both systemic and organ
      specific autoimmune diseases. Autoreactive B cells not only produce
      autoantibodies, but are also specialized to present specific autoantigens
      efficiently to T cells. Furthermore, these B cells can secrete proinflammatory
      cytokines and can amplify the vicious cycle of self-destruction. Thus, B cell
      directed therapies are potentially an important approach for treating autoimmune
      diseases. On the other hand, like T cells, there are subsets of B cells that
      produce anti-inflammatory cytokines and are immunosuppressive. These regulatory B
      cell subsets can protect against and ameliorate autoimmune diseases. Thus
      targeting B cells therapeutically will require this balance to be considered.
      Here we summarize the roles of pathogenic and regulatory B cells and current
      applications of B cell-directed therapy in autoimmune diseases. Considerations
      for future development of B cell-directed therapy for autoimmune diseases have
      also been discussed.

PMID- 19604258
TI  - Translational Mini-Review Series on B Cell-Directed Therapies: The pathogenic
      role of B cells in autoantibody-associated autoimmune diseases--lessons from B
      cell-depletion therapy.
AB  - B cell depletion therapy with rituximab (BCDT) is a licensed treatment for
      rheumatoid arthritis and has shown promising results in the treatment of severe,
      refractory patients with other autoantibody-associated autoimmune diseases
      (AAID). The exact role that B cells play in the pathogenesis of AAID and
      consequently the mechanisms by which BCDT is effective are not known. The two
      more widely discussed hypotheses are that BCDT is effective because it removes
      the precursors of plasma cells producing pathogenic autoantibody species, or
      because it depletes a critical mass of autoreactive B cell clones that present
      antigen to pathogenic autoreactive T cells. This review will focus on the effects
      of BCDT and whether the response of patients with AAID to BCDT could be due
      ultimately to its effects on autoantibodies. A better knowledge of the main role
      that B cells play in the pathogenesis of the different diseases and a better
      understanding of the most likely mechanism of relapse following an earlier
      response to BCDT would help to guide further developments of B cell targeting
      therapies and potentially increase the chance of designing a protocol that could
      induce a long-term remission.

PMID- 19604259
TI  - Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in
      B cell-directed biological therapies for autoimmune disorders.
AB  - B cell-directed therapies are promising treatments for autoimmune disorders.
      Besides targeting CD20, newer B cell-directed therapies are in development that
      target other B cell surface molecules and differentiation factors. An increasing
      number of B cell-directed therapies are in development for the treatment of
      autoimmune disorders. Like rituximab, which is approved as a treatment for
      rheumatoid arthritis (RA), many of these newer agents deplete B cells or target
      pathways essential for B cell development and function; however, many questions
      remain about their optimal use in the clinic and about the role of B cells in
      disease pathogenesis. Other therapies besides rituximab that target CD20 are the
      furthest along in development. Besides targeting CD20, the newer B cell-directed
      therapies target CD22, CD19, CD40-CD40L, B cell activating factor belonging to
      the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is
      being tested in an ever-increasing number of autoimmune disorders and clinical
      studies of rituximab combined with other biological therapies are being pursued
      for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are
      being tested in clinical trials for a variety of autoimmune disorders including
      RA, systemic lupus erythematosus (SLE), Sjogren's syndrome, vasculitis, multiple
      sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the
      inflammatory myopathies (dermatomyositis and polymyositis) and the blistering
      skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical
      studies related to B cell-directed therapies and wealth of new information from
      these trials, much still remains to be discovered about the pathophysiological
      role of B cells in autoimmune disorders.

PMID- 19604260
TI  - Interleukin-17 and systemic lupus erythematosus: current concepts.
AB  - The emerging role of interleukin (IL)-17 as a hallmark proinflammatory cytokine
      of the adaptive immune system, produced primarily by a new T helper cell subset
      termed 'Th17', has received considerable attention. Differentiation of Th17 cells
      is driven by the simultaneous presence of transforming growth factor-beta and
      certain inflammatory cytokines (e.g. IL-6, IL-21), and recent studies have shown
      that inflammation instigated by IL-17-producing cells is central to the
      development and pathogenesis of several human autoimmune diseases and animal
      models of autoimmunity. In this review, we focus on the information regarding IL
      17 and systemic lupus erythematosus (SLE), a chronic autoimmune disease. The work
      that has explored the development and behaviour of IL-17-producing cells in SLE
      is discussed, and different mechanisms by which IL-17 could potentially augment
      inflammation and autoantibody production in the context of SLE are proposed.

PMID- 19604261
TI  - The rise and rise of Staphylococcus aureus: laughing in the face of granulocytes.
AB  - Recent developments in the study of host-pathogen interactions have fundamentally
      altered our understanding of the nature of Staphylococcus aureus infection, and
      previously held tenets regarding the role of the granulocyte are being cast
      aside. Novel mechanisms of pathogenesis are becoming evident, revealing the
      extent to which S. aureus can evade neutrophil responses successfully by
      resisting microbicides, surviving intracellularly and subverting cell death
      pathways. Developing a detailed understanding of these complex strategies is
      especially relevant in light of increasing staphylococcal virulence and
      antibiotic resistance, and the knowledge that dysfunctional neutrophil responses
      contribute materially to poor host outcomes. Unravelling the biology of these
      interactions is a challenging task, but one which may yield new strategies to
      address this, as yet, defiant organism.

PMID- 19604263
TI  - The protective role of antibody responses during Mycobacterium tuberculosis
      infection.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most
      important infectious diseases globally. Immune effector mechanisms that lead to
      protection or development of clinical disease are not fully known. It is
      generally accepted that cell-mediated immunity (CMI) plays a pivotal role in
      controlling Mtb infection, whereas antibody responses are believed to have no
      protective role. This generalization is based mainly on early classical
      experiments that lacked standard protocols, and the T helper type 1 (Th1)/Th2
      paradigm. According to the Th1/Th2 paradigm Th1 cells protect the host from
      intracellular pathogens, whereas Th2 cells protect form extracellular pathogens.
      During the last two decades, the Th1/Th2 paradigm has dominated not only our
      understanding of immunity to infectious pathogens but also our approach to
      vaccine design. However, the last few years have seen major discrepancies in this
      model. Convincing evidence for the protective role of antibodies against several
      intracellular pathogens has been established. Studies of B cell-deficient mice,
      severe combined immunodeficiency (SCID) mice, passive immunization using
      monoclonal (mAb) and polyclonal antibodies and immune responses against specific
      mycobacterial antigens in experimental animals reveal that, in addition to a
      significant immunomodulatory effect on CMI, antibodies play an essential
      protective role against mycobacterial infections. In this review, our current
      understanding of the essential role of antibodies during Mtb infections,
      limitations of the Th1/Th2 model and the unfolding interdependence and mutual
      regulatory relationships between the humoral and CMI will be presented and
      discussed.

PMID- 19604262
TI  - Immunomodulation of innate immune responses by vasoactive intestinal peptide
      (VIP): its therapeutic potential in inflammatory disease.
AB  - Since the late 1970s a number of laboratories have studied the role of vasoactive
      intestinal peptide (VIP) in inflammation and immunity. These studies have
      highlighted the dramatic effect of VIP on immune cell activation and function,
      and studies using animal models of disease have indicated that VIP has
      significant therapeutic and prophylactic potential. This review will focus on the
      effects of VIP on innate immune cell function and discuss the therapeutic
      potential for VIP in inflammatory diseases of humans.

PMID- 19604264
TI  - Functional and clinical consequences of Fc receptor polymorphic and copy number
      variants.
AB  - Receptors for immunoglobulins (Fc receptors) play a central role during an immune
      response, as they mediate the specific recognition of antigens of almost infinite
      diversity by leucocytes, thereby linking the humoral and cellular components of
      immunity. Indeed, engagement of Fc receptors by immunoglobulins initiates a range
      of immunoregulatory processes that might also play a role in disease
      pathogenesis. In the circulation, five main types of immunoglobulins (Ig) exist -
      namely IgG, IgA, IgE, IgM and IgD and receptors with the ability to recognize and
      bind to IgG (Fc gamma receptor family), IgE (Fc epsilon RI and CD23), IgA (CD89;
      Fc alpha/microR) and IgM (Fc alpha/microR) have been identified and
      characterized. However, it is astonishing that nearly all the known human Fc
      receptors display extensive genetic variation with clear implications for their
      function, thus representing a substantial genetic risk factor for the
      pathogenesis of a range of chronic inflammatory disorders.

PMID- 19604265
TI  - The glutamic acid decarboxylase 65 immunoglobulin G subclass profile differs
      between adult-onset type 1 diabetes and latent autoimmune diabetes in adults
      (LADA) up to 3 years after clinical onset.
AB  - Autoantibodies against glutamic acid decarboxylase 65 (GADA) are found frequently
      in patients with autoimmune diabetes. Immunoglobulin (Ig)G(1) is the most
      frequent subclass among the GADA IgG subclasses. IgG(4) is a more common subclass
      in latent autoimmune diabetes in adults (LADA) at clinical onset compared to type
      1 diabetes. The aim of this work was to study the different GADA-IgG subclass
      profiles during a 3-year follow-up in these groups of autoimmune diabetes. Adult
      onset subjects, classified as either type 1 (n = 40) or LADA (n = 43), were
      included in the study. New samples were collected every year from these patients.
      In addition to conventional GADA analyses, GADA-IgG subclasses were also analysed
      with a radioimmunoprecipitation assay using biotin-conjugated antibodies
      (directed against human IgG subclasses and IgM) and streptavidin Sepharose.
      During 3 years' follow-up, all the IgG subclass levels decreased in type 1
      diabetes - IgG(1): P < 0.001; IgG(2): P < 0.001; IgG(3): P < 0.001; IgG(4): P <
      0.05 (Friedman's' test) - while levels remained stable for all four subclasses in
      LADA. GADA IgM, however, decreased in both groups (P < 0.001). Patients with LADA
      have higher GADA IgG(3) and IgG(4) at clinical onset and seem to maintain the
      levels and profile of their IgG subclasses up to 3 years after clinical onset,
      while all the GADA IgG subclass levels decrease in type 1 diabetic patients. This
      indicates a persistent different immune response in LADA compared to type 1
      diabetes and further indicates the difference in pathogenesis.

PMID- 19604266
TI  - Periductal interleukin-17 production in association with biliary innate immunity
      contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis.
AB  - An innate immune response to bacterial components is speculated to be involved in
      the pathogenesis of primary biliary cirrhosis (PBC). Recently, CD4-positive T
      helper type 17 (Th17) cells, characterized by the secretion of interleukin (IL)
      17, have been implicated in the pathogenesis of autoimmune diseases. Human Th17
      cells are generated from Th0 cells by IL-6 and IL-1 beta and maintained by IL-23.
      In this study, the role of IL-17 in PBC and its association with biliary innate
      immunity were examined. Using cultured human biliary epithelial cells (BECs), the
      expression of Th17-related cytokines and chemokines and changes therein on
      treatment with pathogen-associated molecular patterns (PAMPs) and IL-17 were
      examined. Immunohistochemistry for IL-17 and Th17-related cytokines was performed
      using tissue samples of human liver. Consequently, the expression of IL-6, IL-1
      beta, IL-23p19 and IL-23/IL-12p40 mRNAs, and their up-regulation by PAMPs, were
      found in BECs. Moreover, BECs possessed IL-17-receptors and stimulation with IL
      17 induced production of IL-6, IL-1 beta, IL-23p19 and chemokines. Several IL-17
      positive cells had infiltrated damaged bile ducts and the expression of IL-6 and
      IL-1 beta was enhanced in the bile ducts of PBC patients. In conclusion, IL-17
      positive cells are associated with the chronic inflammation of bile ducts in PBC
      which is associated causally with the biliary innate immune responses to PAMPs.

PMID- 19604267
TI  - Differences in virulence and immune response induced in a murine model by
      isolates of Mycobacterium ulcerans from different geographic areas.
AB  - Buruli ulcer (BU) is the third most common mycobacterial disease in
      immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces
      skin ulcers and necrosis at the site of infection. The principal virulence factor
      of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has
      cytotoxic and immunosuppressive activities. We determined the severity of
      inflammation, histopathology and bacillary loads in the subcutaneous footpad
      tissue of BALB/c mice infected with 11 different M. ulcerans isolates from
      diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast)
      induced the highest inflammation, necrosis and bacillary loads, whereas the
      strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe
      (France) and America (Mexico) induced mild inflammation. Subsequently, animals
      were infected with the strain that exhibited the highest (Benin) or lowest
      (Mexico) level of virulence in order to analyse the local immune response
      generated. The Mexican strain, which does not produce mycolactone, induced a
      predominantly T helper type 1 (Th1) cytokine profile with constant high
      expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence
      with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4
      and transforming growth factor (TGF)-beta. The highly virulent strain from Benin
      which produces mycolactone A/B induced the opposite pattern. Thus, different
      local immune responses were found depending on the infecting M. ulcerans strain.

PMID- 19604268
TI  - Association between total immunoglobulin E and antibody responses to naturally
      acquired Ascaris lumbricoides infection and polymorphisms of immune system
      related LIG4, TNFSF13B and IRS2 genes.
AB  - The 13q33-34 region harbours a susceptibility locus to Ascaris lumbricoides,
      although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer
      protective immunity and here we sought to investigate in an endemic population
      whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against
      Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic
      asthmatic patients were analysed for potential relationships between Ascaris
      predisposition and allergy. One thousand and sixty-four subjects from Cartagena,
      Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped
      using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent
      assay. Linear and logistic regressions were used to model effects of genotypes on
      antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher
      IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was
      associated positively with IgG levels against Ascaris extract and IgE levels
      against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE
      levels. Associations held up after correction by population stratification using
      a set of 52 ancestry markers, age, sex and disease status. There was no
      association with asthma or mite sensitization. In a tropical population, LIG4 and
      TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris,
      supporting previous linkage studies implicating the 13q33 region. Our results
      suggest that genes protecting against parasite infections can be different to
      those predisposing to asthma and atopy.

PMID- 19604269
TI  - Short treatment with the tumour necrosis factor-alpha blocker infliximab
      diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma
      cruzi reactivation.
AB  - Tumour necrosis factor (TNF)-alpha is crucial for resistance to Trypanosoma cruzi
      acute infection, but there is scant information on its role during the chronic
      phase. To address this issue, we analysed whether a short treatment with a TNF
      alpha blocker affected the course and characteristics of chronic disease in a rat
      experimental model of T. cruzi infection. An anti-TNF-alpha agent (infliximab)
      was administered during the chronic phase for a period of 4 weeks (3 mg/kg/week),
      while control infected rats were inoculated with saline physiological solution.
      Search for parasites yielded non-successful results in all infected groups,
      irrespective of treatment. Nevertheless, the presence of T. cruzi kDNA in heart
      tissue was detected in infected and infected plus treated animals. Because
      infliximab might induce changes in the anti-parasite cytokine response,
      circulating levels of interleukin (IL)-10, interferon-gamma and nitric oxide were
      evaluated. An increase in IL-10 levels was observed only in the infected group
      treated with the anti-TNF-alpha blocker compared to the remaining groups (P <
      0.05). A clear attenuation of histological damage associated with a diminution of
      cardiac TNF-alpha mRNA expression was observed in the infected and treated
      animals compared to the infected and non-treated group. Blocking of TNF-alpha
      during a relatively short period in chronically infected rats did not lead to
      evident parasite reactivation but reduced myocarditis severity significantly,
      indicating a role of this cytokine in the pathogenesis of chronic myocardial
      damage.

PMID- 19604270
TI  - Inhibition of matrix metalloproteinase-9 activity improves coronary outcome in an
      animal model of Kawasaki disease.
AB  - Kawasaki disease (KD) is the leading cause of acquired heart disease of children
      in North America. It is characterized by a massive immune activation and multi
      system vasculitis, which evolves into a site-specific inflammatory response
      focused at the coronary arteries. Coronary artery (CA) inflammation leads to
      elastin breakdown, destruction of the vessel wall and aneurysm formation. We have
      demonstrated recently the pivotal role of tumour necrosis factor (TNF)-alpha
      mediated matrix metalloproteinase (MMP)-9 activity in the pathogenesis of elastin
      breakdown in a murine model of KD, Lactobacillus casei cell wall extract-induced
      coronary arteritis. Using this model, we evaluated the in vitro effects of
      doxycycline, an antibiotic with MMP inhibitory function, in modulating key
      pathogenic stages of disease leading to CA damage. Doxycycline inhibits T cell
      activation and TNF-alpha production in peripheral immune cells, as assessed by
      thymidine incorporation and a TNF bioassay respectively. Additionally,
      doxycycline inhibits directly MMP-9 enzymatic activity derived from TNF-alpha
      stimulated vascular smooth muscle cells as assayed by zymography. More
      importantly, in vivo treatment of Lactobacillus casei cell wall extract (LCWE)
      injected mice with doxycycline reduces significantly the incidence of CA elastin
      breakdown and reduces loss of elastin. Therefore, doxycycline can mitigate TNF
      alpha-induced MMP-9-mediated coronary elastin breakdown and improve coronary
      outcome. Agents with the ability to inhibit both inflammation and the downstream
      effects of inflammation, such as MMP-9 activity, offer a promising therapeutic
      strategy for the management of children with KD.

PMID- 19604271
TI  - Thalidomide has a therapeutic effect on interstitial lung fibrosis: evidence from
      in vitro and in vivo studies.
AB  - The objective of this study was to investigate the effects of thalidomide (THD)
      on interstitial lung fibrosis (ILF). In vitro, human fetal lung fibroblast (HFL
      F) to myofibroblast (MF) trans-differentiation was induced by transforming growth
      factor (TGF)-beta1. The effects of THD on trans-differentiation process or
      differentiated MF were evaluated by measuring hydroxyproline (HYP) content by
      alkaline hydrolysis colorimetry, alpha-smooth muscle actin (alpha-SMA) protein by
      Western blot and alpha-SMA and pro-collagen III mRNA expressions by semi
      quantitative reverse transcription-polymerase chain reaction; in vivo, a mouse
      model of ILF was generated by daily subcutaneous injection of bleomycin (BLM) in
      female C3H mice. Gastric perfusion of THD began 1 week prior to injection and
      lasted for 8 weeks. Lung specimens were harvested at different time-points (1, 4,
      6 and 8 weeks) for pathology and immunohistochemistry examination. The HYP
      content, alpha-SMA and pro-collagen III mRNA expressions were also assessed. THD
      inhibited the up-regulation of HYP protein, pro-collagen III mRNA and alpha-SMA
      protein induced by TGF-beta1 in HFL-F cells, and additionally inhibited pro
      collagen III mRNA expression on trans-differentiated MF. THD reduced HYP
      synthesis in the lung tissues of BLM-treated mice at week 4, and slightly reduced
      the numbers of alpha-SMA-positive cells. THD had an effect on ILF models both in
      vitro and in vivo.

PMID- 19604273
TI  - Emerging viruses and the significance of climate change.

PMID- 19604272
TI  - T helper type 17-related cytokine expression is increased in the bronchial mucosa
      of stable chronic obstructive pulmonary disease patients.
AB  - There are increased numbers of activated T lymphocytes in the bronchial mucosa of
      stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17
      (Th17) cells release interleukin (IL)-17 as their effector cytokine under the
      control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some
      chronic inflammatory conditions. To investigate the expression of interleukin
      (IL)-17A, IL-17F, IL-21, IL-22 and IL-23 and of retinoic orphan receptor RORC2, a
      marker of Th17 cells, in bronchial biopsies from patients with stable COPD of
      different severity compared with age-matched control subjects. The expression of
      IL-17A, IL-17F, IL-21, IL-22, IL-23 and RORC2 was measured in the bronchial
      mucosa using immunohistochemistry and/or quantitative polymerase chain reaction.
      The number of IL-22(+) and IL-23(+) immunoreactive cells is increased in the
      bronchial epithelium of stable COPD compared with control groups. In addition,
      the number of IL-17A(+) and IL-22(+) immunoreactive cells is increased in the
      bronchial submucosa of stable COPD compared with control non-smokers. In all
      smokers, with and without disease, and in patients with COPD alone, the number of
      IL-22(+) cells correlated significantly with the number of both CD4(+) and CD8(+)
      cells in the bronchial mucosa. RORC2 mRNA expression in the bronchial mucosa was
      not significantly different between smokers with normal lung function and COPD.
      Further, we report that endothelial cells express high levels of IL-17A and IL
      22. Increased expression of the Th17-related cytokines IL-17A, IL-22 and IL-23 in
      COPD patients may reflect their involvement, and that of specific IL-17-producing
      cells, in driving the chronic inflammation seen in COPD.

PMID- 19604274
TI  - Influence of climate change on the incidence and impact of arenavirus diseases: a
      speculative assessment.
AB  - The current worldwide incidence of viral haemorrhagic fevers caused by
      arenaviruses is briefly reviewed. The recently published Assessment Report of the
      Intergovernmental Panel on Climate Change has described the changes in global
      climate that are expected to occur over the course of the present century and
      beyond. Climate modelling and forecasting have not yet reached the stage where
      confident predictions of regional changes at the level of a virus endemic area
      can be made. However, in the regions where pathogenic arenaviruses now circulate,
      significant effects are likely to include increases in surface temperature,
      changes in the extent and distribution of rainfall, the occurrence of extreme
      weather events, glacier retreat, and coastal flooding as a result of sea level
      rise. The possible impact of these changes on the geographical location and the
      incidence of arenavirus diseases and its human impact are discussed.

PMID- 19604275
TI  - Bunyaviruses and climate change.
AB  - It is generally accepted that the planet is undergoing climatic changes, and
      'climate change' has become the scapegoat for many catastrophes, including
      infectious disease outbreaks, as acknowledged by Randolph and Ergonul, who state
      'Climate change is the current ubiquitous explanation for increased incidence of
      infections of many sorts' (Future Virology 2008; 3: 303-306). However, as these
      authors argue, this is a highly simplistic view and, indeed, there is a complex
      network of factors that are responsible for disease emergence and re-emergence.
      In this short review, the role that climate change could play in the emergence of
      bunyavirus disease is considered, using a few selected examples.

PMID- 19604276
TI  - Hantaviruses and climate change.
AB  - Most hantaviruses are rodent-borne emerging viruses. They cause two significant
      human diseases, haemorrhagic fever with renal syndrome in Asia and Europe, and
      hantavirus cardiopulmonary syndrome in the Americas. Very recently, several novel
      hantaviruses with unknown pathogenic potential have been identified in Africa and
      in a variety of insectivores (shrews and a mole). Because there is very limited
      information available on the possible impact of climate change on all of these
      highly dangerous pathogens, it is timely to review this aspect of their
      epidemiology. It can reasonably be concluded that climate change should influence
      hantaviruses through impacts on the hantavirus reservoir host populations. We can
      anticipate changes in the size and frequency of hantavirus outbreaks, the
      spectrum of hantavirus species and geographical distribution (mediated by changes
      in population densities), and species composition and geographical distribution
      of their reservoir hosts. The early effects of global warming have already been
      observed in different geographical areas of Europe. Elevated average temperatures
      in West-Central Europe have been associated with more frequent Puumala hantavirus
      outbreaks, through high seed production (mast year) and high bank vole densities.
      On the other hand, warm winters in Scandinavia have led to a decline in vole
      populations as a result of the missing protective snow cover. Additional effects
      can be caused by increased intensity and frequency of extreme climatic events, or
      by changes in human behaviour leading to higher risk of human virus exposure.
      Regardless of the extent of climate change, it is difficult to predict the impact
      on hantavirus survival, emergence and epidemiology. Nevertheless, hantaviruses
      will undoubtedly remain a significant public health threat for several decades to
      come.

PMID- 19604277
TI  - Norovirus seasonality and the potential impact of climate change.
AB  - Seasonal variation in norovirus infection is a recognized but poorly understood
      phenomenon. It is likely to be based on biological, environmental and behavioural
      factors that regulate transmission, virulence and persistence of the virions in
      host populations. Understanding the seasonal dependency of norovirus infection is
      an important step towards understanding its epidemiology, with subsequent
      implementation of efficient measures of surveillance and control. Whether or not
      climate change could influence the seasonal patterns of norovirus infection, by
      impacting on its transmission, geographic distribution and prevalence, has not
      yet been considered. This review addresses the question.

PMID- 19604278
TI  - The importance of strain variation in virulence of Candida dubliniensis and
      Candida albicans: results of a blinded histopathological study of invasive
      candidiasis.
AB  - The pathogenic yeast Candida dubliniensis is increasingly reported as a cause of
      systemic fungal infections. We compared the virulence of 9 clinical bloodstream
      isolates of C. dubliniensis with 3 C. albicans isolates in a murine model of
      invasive candidiasis. Quantification of organisms and inflammatory changes in
      kidneys of infected animals were evaluated in a blinded, systematic manner.
      Average 7-day mortality among animals infected with C. dubliniensis was 21.0%
      (33/157 animals; range for strains: 0-57.1%); and with C. albicans 23.2%, (23/99
      animals; range for strains: 6.7-85.0%) (p 0.65). Greater strain variation was
      noted within species than between the two species. Both species comprised strains
      of either high or low virulence, and six of the nine C. dubliniensis strains
      showed negligible virulence. Colony counts determined on samples from liver and
      kidneys did not differ between species. According to histopathological analysis,
      C. dubliniensis produced significantly lower levels of hyphae than C. albicans (p
      <0.001). Candida albicans caused a greater inflammatory response in kidneys (p
      <0.001) and was more commonly associated with granulomatous inflammation (p
      0.003) and greater mononuclear infiltrate (p <0.001). According to multivariate
      analysis, increasing tissue burden of both hyphal forms (p 0.032) and yeasts (p
      0.016) was independently associated with death, whereas higher levels of
      mononuclear cells were protective (p <0.001). The results suggest a great overlap
      between the virulence properties of C. dubliniensis and C. albicans. Both yeast
      and hyphal forms are independently associated with mortality, suggesting similar
      virulence for both. The source of the fungal isolates may be a neglected
      confounding factor in virulence studies in animal models.

PMID- 19604279
TI  - Viral agents of acute gastroenteritis in hospitalized children in Greece.
AB  - A 6-year study of stool samples from 4604 children hospitalized for acute
      gastroenteritis was conducted to investigate the role of enteric viruses as a
      cause of gastroenteritis in north-west Greece. Rotaviruses, noroviruses,
      adenoviruses and astroviruses were detected in 21.35%, 4%, 3.5% and 2.35%,
      respectively, by enzyme immunoassays and molecular techniques. Molecular
      techniques enhanced overall diagnostic efficacy by 2.5%, and by c. 10% each for
      rotavirus and adenovirus. Rotavirus was the leading cause of viral
      gastroenteritis, usually associated with severe illness. Mixed infections were
      found in 4.4% of positive specimens, and rotavirus plus astrovirus represented
      the most frequent co-infection (55.5%). This first study on the epidemiology of
      viral gastroenteritis in Greece shows that recent advances in the diagnosis of
      viral enteropathogens may have only marginal effects on overall diagnostic
      efficacy, and thus the impact of viral agents causing sporadic gastroenteritis in
      public health cannot be fully evaluated.

PMID- 19604280
TI  - Failures and complications in patients with birth defects restored with fixed
      dental prostheses and single crowns on teeth and/or implants.
AB  - OBJECTIVES: To assess retrospectively, over at least 5 years, the incidences of
      technical and biological complications and failures in young adult patients with
      birth defects affecting the formation of teeth. MATERIAL AND METHODS: All
      insurance cases with a birth defect that had crowns and fixed dental prostheses
      (FDPs) inserted more than 5 years ago were contacted and asked to participate in
      a reexamination. RESULTS: The median age of the patients was 19.3 years (range
      16.6-24.7 years) when prosthetic treatment was initiated. Over the median
      observation period of 15.7 years (range 7.4-24.9 years) and considering the
      treatment needs at the reexamination, 19 out of 33 patients (58%) with
      reconstructions on teeth remained free from all failures or complications. From
      the patients with FDPs and single unit crowns (SCs) on implants followed over a
      median observation period of 8 years (range 4.6-15.3 years), eight out of 17% or
      47% needed a retreatment or repair at some point due to a failure or a
      complication. From the three groups of patients, the cases with
      amelogenesis/dentinogenesis imperfecta demonstrated the highest failure and
      complication rates. In the cases with cleft lip, alveolus and palate (CLAP) or
      hypodontia/oligodontia, 71% of the SCs and 73% of the FDPs on teeth (FDP T)
      remained complication free over a median observation period of about 16 years.
      Sixty-two percent of the SCs and 64% of the FDPs on implants remained
      complication free over 8 years. Complications occurred earlier with implant
      supported reconstructions. CONCLUSIONS: Because healthy, pristine teeth can be
      left unprepared, implant-supported SCs and FDPs are the treatment choice in young
      adults with birth defects resulting in tooth agenesis and in whom the edentulous
      spaces cannot be closed by means of orthodontic therapy. However, the trend for
      earlier and more frequent complications with implant-supported reconstructions in
      young adults, expecting many years of function with the reconstructions, has to
      be weighed against the benefits of keeping teeth unprepared. In cases with CLAP
      in which anatomical conditions render implant placement difficult and in which
      teeth adjacent to the cleft require esthetic corrections, the conventional FDP T
      still remains the treatment of choice.

PMID- 19604281
TI  - Surface-modified zirconia implants: tissue response in rabbits.
AB  - AIM: To evaluate the bone tissue response to zirconia implants with three
      different surface modifications in comparison with the oxidized titanium surface
      with the goal to optimize osseointegration in terms of strength and speed.
      MATERIALS AND METHODS: A total of 18 rabbits with 143 implants were used. One
      hundred and twenty-three were threaded zirconia ceramic implants with three
      different surface topographies and 20 modified titanium oxide implants were
      controls. Each rabbit received eight implants and sacrificed after 3 weeks. The
      removal torque test (RTQ) and histology were performed. RESULTS: Sixteen out of
      18 rabbits completed the study with a total of 110 implants. No statistical
      significance was observed between the chemical modification implants compared
      with the topographically modified zirconia implant in terms of interfacial shear
      strength proven by the RTQ applied. No statistical significance was also observed
      in the bone-to-implant contact between the zirconia implants and the control
      oxidized implants. CONCLUSIONS: The findings suggest that additional specific
      chemical modifications of the topographically modified zirconia implants do not
      seem to enhance the bone-to-implant contact and appear not to increase the
      interfacial shear strength.

PMID- 19604282
TI  - Unconventional implant treatment: I. Implant placement in contact with ankylosed
      root fragments. A series of five case reports.
AB  - OBJECTIVE: Implant treatment presumes that implants are placed in bone, without
      any contact with root. At ankylosed teeth, complete root removal is often
      invasive; subsequently, the sites require additional augmentation procedures to
      complete the treatment. The aim of this paper is to report on a series of five
      cases that have been treated with an approach that avoided extractive invasive
      surgery and bone damage. MATERIAL AND METHODS: The procedure consisted of
      preparing the osteotomy site by drilling through the root. At the end of the
      drilling sequence, the root fragments that were not removed were deliberately
      left at the osteotomy site. Their mobility was checked with a dental pick and
      when stable an implant was placed in contact with them. The sites were required
      to be asymptomatic and inflammation free. Ankylosed teeth were replaced with 13
      15-mm-long Osseotite implants, four in the anterior maxilla and one in the
      anterior mandible. RESULTS: All implants healed uneventfully; they have been now
      loaded for a period of 12-42 months. On peri-apical radiographs, appearance of
      the bone-implant interface was similar to osseointegrated implants. The remaining
      root fragments were visible, in contact with the implants; no specific
      pathological sign could be detected. A limited resorption of dentine was found at
      one site after 4 years. CONCLUSION: This series of cases suggests that implants
      placed in contact with ankylosed root fragments might not interfere with implant
      integration or harm occlusal function, at least in the mid-term. More cases are
      warranted before this procedure might be considered as a reliable clinical option
      when, at ankylosed teeth, one wishes to avoid an invasive extraction surgery.

PMID- 19604283
TI  - Titanium allergy associated with dental implant failure.

PMID- 19604284
TI  - Diagnosis of Hirschsprung's Disease: an age-related approach in children below or
      above one year.
AB  - AIM: The aim of this study was to evaluate the effectiveness of a differential
      diagnostic approach to Hirshchsprung's Disease (HD) on the basis of age. METHOD:
      Data on 185 consecutive children with suspected HD were subjected to an age
      related diagnostic approach. The patients were divided into two groups according
      to age (A < 1 year; B > 1 year). Children in Group A had rectal suction biopsy
      (RSB) and contrast enema (CE), and in Group B anorectal manometry (ARM) was
      performed. Patients with a normal recto-anal inhibitory reflex (RAIR) underwent
      bowel disimpaction and medical treatment. Only selected cases in Group B
      underwent RSB and CE. RESULTS: In Group A (18 patients) CE showed a colonic
      transitional zone in three patients, whereas RSB led to the diagnosis of HD in
      nine. In Group B (167 patients) ARM was not possible in seven patients and it was
      normal in 140 (normal anal sphincter pressure: 83; hypertonia of the internal
      anal sphincter: 57). The RAIR was negative in 20 patients. RSB performed in 31
      children in Group B confirmed HD in three patients. CONCLUSIONS: For patients
      with a neonatal onset of constipation RSB is the best diagnostic technique.
      Chronic constipation is rarely due to HD and ARM is a useful non-invasive
      screening tool.

PMID- 19604285
TI  - Downregulation of caspase-9 is a frequent event in patients with stage II
      colorectal cancer and correlates with poor clinical outcome.
AB  - OBJECTIVE:  To evaluate the clinical significance of caspase-9 mRNA expression
      and investigate its prognostic value in stage II colorectal cancer. METHOD:
      Quantitative real-time RT-PCR was used to analyse caspase-9 mRNA expression in
      cancer tissue and corresponding normal mucosa from 120 patients. RESULTS:
      Compared with normal mucosa, the expression of caspase-9 mRNA was found to be
      downregulated in cancer tissue (P = 0.001). Poorly differentiated cancer showed
      lower mRNA expression than cancer with greater differentiation (P = 0.031). The
      Kaplan-Meier survival analysis demonstrated that patients with downregulated
      caspase-9 showed a worse overall survival (P = 0.012) and disease-free survival
      (P = 0.022). Cox's proportional hazards regression model confirmed that
      expression of caspase-9 was the strongest prognostic factor in stage II
      colorectal cancer. CONCLUSION: The mRNA expression of caspase-9 can be used as an
      independent prognostic factor for patients with stage II colorectal cancer.

PMID- 19604286
TI  - Long-term compliance with endoscopic surveillance for familial adenomatous
      polyposis.
AB  - AIM: The study assessed compliance of patients with familial adenomatous
      polyposis (FAP) with endoscopic surveillance. METHOD: In this nationwide, cross
      sectional study, individuals from FAP families registered with the Netherlands
      Foundation for the Detection of Hereditary Tumours were invited to complete a
      questionnaire on endoscopic screening experiences. RESULTS:  A total of 328
      individuals were eligible for the study of whom 85 were at risk for FAP, 108 had
      an intact rectum after a colectomy with ileorectal anastomosis (IRA), and 135 had
      had a pouch following a proctocolectomy with ileoanal anastomosis (IPAA). Based
      on medical record data, 20% of the at-risk group and 26% of the IRA-group were
      found to be undercompliant with surveillance advice which was associated
      significantly with perceived self-efficacy, use of sedatives during surveillance,
      pain after surveillance and low perceived benefits of surveillance (P < 0.05).
      CONCLUSION: One in five individuals at risk for FAP and one in four with a
      retained rectum are undercompliant with screening advice. We recommend that
      sedatives should be patient-tailored for FAP individuals undergoing surveillance
      and that adequate pain medication be provided after endoscopy.

PMID- 19604287
TI  - Adept (Icodextrin 4%): a tale of caution.

PMID- 19604288
TI  - Stoma complications: a literature overview.
AB  - Stoma formation is a commonly performed procedure in colorectal surgery as a part
      of operations performed for malignant- and inflammatory bowel disease. Stoma
      formation is a simple, but not trivial, undertaking. When performed badly, it can
      leave the patients with a legacy of complications such as leakage, prolapse,
      parastomal hernia and retraction. Various studies have reported a complication
      rate of 21-70%. We performed a literature search using the Medline, Ovid and
      Google scholar database for all the articles published between January 1980 and
      December 2008. The search terms used were colostomy, ileostomy, stoma, parastomal
      hernia, stenosis, prolapse, necrosis and complications. The following article
      summarizes the common complications associated with stomas.

PMID- 19604289
TI  - Artificial neural networks to predict presence of significant pathology in
      patients presenting to routine colorectal clinics.
AB  - AIM: Artificial neural networks (ANNs) are computer programs used to identify
      complex relations within data. Routine predictions of presence of colorectal
      pathology based on population statistics have little meaning for individual
      patient. This results in large number of unnecessary lower gastrointestinal
      endoscopies (LGEs - colonoscopies and flexible sigmoidoscopies). We aimed to
      develop a neural network algorithm that can accurately predict presence of
      significant pathology in patients attending routine outpatient clinics for
      gastrointestinal symptoms. METHOD: Ethics approval was obtained and the study was
      monitored according to International Committee on Harmonisation - Good Clinical
      Practice (ICH-GCP) standards. Three-hundred patients undergoing LGE prospectively
      completed a specifically developed questionnaire, which included 40 variables
      based on clinical symptoms, signs, past- and family history. Complete data sets
      of 100 patients were used to train the ANN; the remaining data was used for
      internal validation. The primary output used was positive finding on LGE,
      including polyps, cancer, diverticular disease or colitis. For external
      validation, the ANN was applied to data from 50 patients in primary care and also
      compared with the predictions of four clinicians. RESULTS: Clear correlation
      between actual data value and ANN predictions were found (r = 0.931; P = 0.0001).
      The predictive accuracy of ANN was 95% in training group and 90% (95% CI 84-96)
      in the internal validation set and this was significantly higher than the
      clinical accuracy (75%). ANN also showed high accuracy in the external validation
      group (89%). CONCLUSION: Artificial neural networks offer the possibility of
      personal prediction of outcome for individual patients presenting in clinics with
      colorectal symptoms, making it possible to make more appropriate requests for
      lower gastrointestinal endoscopy.

PMID- 19604290
TI  - An alternative to conventional hand-sewing colocolic anastomosis: anastomosis
      with absorbable surgical barrier film without sutures.
AB  - AIM: As a result of its high morbidity and mortality rates, anastomotic leakage
      is one of the most feared complications in colorectal surgery. Therefore, this
      issue is one of the most relevant in colorectal surgery and a lot of work has
      been conducted to research it. The aim of this experimental study was to compare
      colocolic anastomosis performed by using absorbable surgical barrier film without
      suture and conventional anastomosis performed by hand-sewing technique in terms
      of anastomosis safety. METHOD: In this study, 40 Norway Wistar Albino 3-month-old
      female rats were used. Each weighed between 250 and 300g. The rates were divided
      into two groups, a control group and an experimental group. Full-thickness
      incisions were made on the ascending colon of both groups of rats. The control
      group's anastomoses were conducted using a hand-sewn technique consisting of one
      layer of nonabsorbable sutures (Gambee suture). The experimental group's
      anastomoses were performed using absorbable surgical barrier film without
      sutures. Afterwards, sample pieces of the anastomosis area were taken from all
      rats on either the 3rd or the 7th day following the operation, resulting in
      subgroups that led to a total of four test groups. The samples taken were
      subjected first to an anastomosis bursting pressure test followed by
      histopathological examinations and a test to detect the levels of hydroxyproline
      in the tissue. RESULTS: The control groups (groups 1 and 3) had average
      anastomotic bursting pressures of 33.0+/-9.49mmHg and 146.0+/-15.06mmHg
      respectively, whereas experimental groups (groups 2 and 4) had average
      anastomotic bursting pressures of 58.0+/-10.33mmHg and 190.0+/-25.82mmHg
      respectively. Mann-Whitney U-test analysis of the bursting pressure values
      indicates the differences between groups 1 and 2 (3rd day postoperatively) and
      groups 3 and 4 (7th day postoperatively) to be statistically significant
      (P=0.0001 and P=0.0003 respectively). Values obtained from histopathological
      staging conducted according to the Ehrlich-Hunt model where the evaluation
      criteria in this model are: amount of inflammatory cells, fibroblasts,
      neovascularization and collagen and which were analysed using the Mann-Whitney U
      test have shown no significant difference between 3rd day postoperatively groups
      1 and 2 (P=0.579) while the difference between 7th day postoperatively groups 3
      and 4 was found to be significant (P=0.023). Average levels of hydroxyproline in
      the tissue were 88.18+/-8.04mg/l for group 1, 56.31+/-5.40mg/l for group 2,
      135.0+/- 6.30mg/l for group 3 and 100.2+/-15.42mg/l for group 4. Analysis of
      values in the groups using the Mann-Whitney U-test indicate a significant
      difference (P < 0.0001) both between groups 1 and 2 and between groups 3 and 4.
      CONCLUSION: The use of absorbable surgical barrier film without sutures for
      colocolic anastomosis in rats may be safe.

PMID- 19604291
TI  - Ileal pouch-anal anastomosis after stapled haemorrhoidopexy for unrecognized
      ulcerative colitis.

PMID- 19604292
TI  - Fistulectomy and sphincteric reconstruction for complex cryptoglandular fistulas.
AB  - OBJECTIVE: Complex anal fistulas (CFs) are difficult to treat. Endoanal
      advancement flap (EAF) is one of the standard treatment options for such clinical
      conditions. Immediate sphincter repair after fistulectomy (ISR) is not commonly
      performed because of the fear of causing postoperative incontinence. The
      objective of this study was to compare the results of both techniques. METHOD: We
      retrospectively analysed a prospectively entered database composed of 146
      patients (112 M; 34 F), undergoing operations for CF of cryptoglandular origin.
      The patients were divided in two groups: Group A: (EAF); n = 71 patients; Group
      B: (ISR); n = 75 patients. RESULTS: Forty-two fistulas (28.7%) were recurrent, 98
      trans-sphincteric (TS) and 37 suprasphincteric (SS). Twenty-six (17.7%) patients
      had some degree of preoperative continence disturbances, 11 in Group A vs 15 in
      Group B (P = 0.47). After a mean follow up of 13 months (12-60), fistula
      persisted or recurred in 13 (18.3%) patients in Group A vs eight (10.6%) in Group
      B (P = 0.19) irrespective of the fistula type (TS or SS). Thirty-one (43.6%)
      patients in Group A vs 16 (21.3%) in Group B presented postoperative continence
      disturbances (P < 0.001). No changes were observed with the Faecal Incontinence
      Quality of Life Scale (FIQLS). Group A patients had a significant reduction of
      maximal rest pressure after surgery. After ISR, no significant changes in
      pressures were observed. CONCLUSION: Immediate sphincter repair can be a
      therapeutic option in selected cases of CF, mainly when associated with
      incontinence or increased risk factors.

PMID- 19604293
TI  - Commentary: How obesity and physical activity contribute to colorectal cancer.

PMID- 19604294
TI  - Identifying anomalous reports of putatively extinct species and why it matters.
AB  - As species become very rare and approach extinction, purported sightings can stir
      controversy, especially when scarce management resources are at stake. We used
      quantitative methods to identify reports that do not fit prior sighting patterns.
      We also examined the effects of including records that meet different evidentiary
      standards on quantitative extinction assessments for four charismatic bird
      species that might be extinct: Eskimo Curlew (Numenius borealis), Ivory-billed
      Woodpecker (Campephilus principalis), Nukupu'u (Hemignathus lucidus), and O'ahu
      'Alauahio (Paroreomyza maculata). For all four species the probability of there
      being a valid sighting today, given the past pattern of verified sightings, was
      estimated to be very low. The estimates of extinction dates and the chance of new
      sightings, however, differed considerably depending on the criteria used for data
      inclusion. When a historical sighting record lacked long periods without
      sightings, the likelihood of new sightings declined quickly with time since the
      last confirmed sighting. For species with this type of historical record,
      therefore, new reports should meet an especially high burden of proof to be
      acceptable. Such quantitative models could be incorporated into the International
      Union for Conservation of Nature's Red List criteria to set evidentiary standards
      required for unconfirmed sightings of "possibly extinct" species and to
      standardize extinction assessments across species.

PMID- 19604295
TI  - How to build an efficient conservation fence.
AB  - Barriers are used to achieve diverse objectives in conservation and biosecurity.
      In conservation management, fences are often erected to exclude introduced
      predators and to contain diseased animals or invasive species. Planning an
      efficient conservation fence involves a number of decisions, including the size
      and design of the enclosure. We formulated the first general framework for
      building a fence that minimizes long-term management costs by balancing the
      expense of constructing a more secure barrier against the costs of coping with
      more frequent failures. The approach systematically considers the range of
      potential solutions to a well-defined fencing problem and results in a solution
      that maximizes conservation return on investment. We illustrated this method by
      designing efficient fences to address two different conservation goals: exclusion
      of invasive predators from populations of threatened eastern barred bandicoots
      (Perameles gunnii) and maintenance of isolated populations of healthy Tasmanian
      devils (Sarcophilus harrisii). A systematic approach to conservation fencing
      allows the best fence design to be chosen quantitatively and defensibly. It also
      facilitates conservation decisions at a strategic level by allowing fencing to be
      compared transparently with alternative conservation management actions.

PMID- 19604296
TI  - A generic impact-scoring system applied to alien mammals in Europe.
AB  - We present a generic scoring system that compares the impact of alien species
      among members of large taxonomic groups. This scoring can be used to identify the
      most harmful alien species so that conservation measures to ameliorate their
      negative effects can be prioritized. For all alien mammals in Europe, we assessed
      impact reports as completely as possible. Impact was classified as either
      environmental or economic. We subdivided each of these categories into five
      subcategories (environmental: impact through competition, predation,
      hybridization, transmission of disease, and herbivory; economic: impact on
      agriculture, livestock, forestry, human health, and infrastructure). We assigned
      all impact reports to one of these 10 categories. All categories had impact
      scores that ranged from zero (minimal) to five (maximal possible impact at a
      location). We summed all impact scores for a species to calculate "potential
      impact" scores. We obtained "actual impact" scores by multiplying potential
      impact scores by the percentage of area occupied by the respective species in
      Europe. Finally, we correlated species' ecological traits with the derived impact
      scores. Alien mammals from the orders Rodentia, Artiodactyla, and Carnivora
      caused the highest impact. In particular, the brown rat (Rattus norvegicus),
      muskrat (Ondathra zibethicus), and sika deer (Cervus nippon) had the highest
      overall scores. Species with a high potential environmental impact also had a
      strong potential economic impact. Potential impact also correlated with the
      distribution of a species in Europe. Ecological flexibility (measured as number
      of different habitats a species occupies) was strongly related to impact. The
      scoring system was robust to uncertainty in knowledge of impact and could be
      adjusted with weight scores to account for specific value systems of particular
      stakeholder groups (e.g., agronomists or environmentalists). Finally, the scoring
      system is easily applicable and adaptable to other taxonomic groups.

PMID- 19604297
TI  - Transvalued species in an African forest.
AB  - We combined ethnographic investigations with repeated ecological transect surveys
      in the Dzanga-Sangha Dense Forest Reserve (RDS), Central African Republic, to
      elucidate consequences of intensifying mixed use of forests. We devised a
      framework for transvaluation of wildlife species, which means the valuing of
      species on the basis of their ecological, economic, and symbolic roles in human
      lives. We measured responses to hunting, tourism, and conservation of two
      transvalued species in RDS: elephants (Loxodonta cyclotis) and gorillas (Gorilla
      gorilla). Our methods included collecting data on encounter rates and habitat use
      on line transects. We recorded cross-cultural variation in ideas about and
      interactions with these species during participant observation of hunting and
      tourism encounters and ethnographic interviews with hunters, conservation staff,
      researchers, and tourists. Ecologically, gorillas used human-modified landscapes
      successfully, and elephants were more vulnerable than gorillas to hunting.
      Economically, tourism and encounters with elephants and gorillas generated
      revenues and other benefits for local participants. Symbolically, transvaluation
      of species seemed to undergird competing institutions of forest management that
      could prove unsustainable. Nevertheless, transvaluation may also offer
      alternatives to existing social hierarchies, thereby integrating local and
      transnational support for conservation measures. The study of transvaluation
      requires attention to transnational flows of ideas and resources because they
      influence transspecies interactions. Cross-disciplinary in nature, transvalution
      of species addresses the political and economic challenges to conservation
      because it recognizes the varied human communities that shape the survival of
      wildlife in a given site. Transvaluation of species could foster more socially
      inclusive management and monitoring approaches attuned to competing economic
      demands, specific species behaviors, and human practices at local scales.

PMID- 19604298
TI  - Melatonin--a pleiotropic molecule involved in pathophysiological processes
      following organ transplantation.
AB  - Mammals adjust their physiology in response to seasonal changes to environment
      (i.e. photoperiod, temperature, food availability). These changes are thought to
      predominantly occur for the conservation of energy during winter, by pervasive
      changes such as the inhibition of reproduction. Previous reports have suggested
      that circannual changes also occur to the immune system. In mammals, this
      chronological effect may be dependent on photoperiod, and evidence exists to
      suggest that there is a great deal of immune variation in response to light, or
      circadian rhythm. This is a clinically relevant, yet under-reported area of human
      transplantation. The aim of this review is to discuss immune variation, with
      specific emphasis on melatonin secretion, in the context of organ rejection,
      infection, neoplasia formation, and immunosuppression.

PMID- 19604299
TI  - Th9 and allergic disease.
AB  - Helper CD4(+) T-cell subsets have improved our understanding of adaptive immunity
      in humans and in animal models of disease. These include T helper type 1 (Th1),
      Th2 and the interleukin-17 (IL-17) -producing population 'Th17'. Th2 cells have
      been described as orchestrating the immune response in allergic disease based on
      studies with patient samples and animal models. The cytokine IL-9 has largely
      been regarded as a Th2 cytokine that makes multifocal contributions to allergic
      disease. Recent data suggest that under certain conditions relevant to chronic
      disease (IL-4 and transforming growth factor-beta), a distinct population of IL-9
      producing 'Th9' helper T cells can exist. The contribution of Th9 cells in
      allergic disease is currently unknown, and this review will propose a model for
      how these cells may regulate chronic allergic inflammation.

PMID- 19604300
TI  - mTOR: taking cues from the immune microenvironment.
AB  - The ultimate outcome of T cell receptor recognition is determined by the context
      in which the antigen is encountered. In this fashion both antigen-presenting
      cells and T cells must integrate multiple environmental cues in the form of
      pathogen-associated molecular patterns, cytokines and accessory molecule signals.
      The mammalian target of rapamycin (mTOR) is an evolutionarily conserved
      serine/threonine kinase that plays a central role in integrating environmental
      signals critical to regulating metabolism and cell survival. In this paper we
      review the data demonstrating that mTOR integrates signals from the immune
      microenvironment and therefore facilitates the generation of the adaptive immune
      response. Specifically, we review the role of mTOR in promoting dendritic cell
      activation and maturation, in regulating full T cell activation versus anergy,
      and influencing the induction of regulatory T cells.

PMID- 19604302
TI  - Enhancement of T-cell-mediated anti-tumour immunity via the ectopically expressed
      glucocorticoid-induced tumour necrosis factor receptor-related receptor ligand
      (GITRL) on tumours.
AB  - Glucocorticoid-induced tumour necrosis factor receptor-related receptor (GITR)
      costimulates functions of both effector and regulatory T cells. The
      administration of agonistic anti-GITR monoclonal antibodies efficiently enhances
      various T-cell-mediated immune responses; however, it is unknown to what extent
      the ligand of GITR (GITRL) contributes to T-cell responses. We investigated the
      involvement of endogenously expressed GITRL on dendritic cells and ectopically
      expressed GITRL on tumours in T-cell-mediated immunity. Expression of GITRL on
      dendritic cells in secondary lymphoid organs was limited, and treatment with anti
      GITRL monoclonal antibodies did not substantially affect T-cell-mediated immunity
      to alloantigens, a specific protein antigen (ovalbumin), or tumour antigens. The
      introduction of GITRL promoted anti-tumour immunity in four tumour models. Tumour
      associated GITRL greatly augmented the effector function of CD8(+) T cells and
      enhanced the contribution of CD8(+) T cells. These events reduced the crucial
      contribution of CD25(+) CD4(+) regulatory T cells, which were found to inhibit
      immunity against tumours lacking GITRL. Peritumoral injection of GITRL tumour
      vaccine efficiently inhibited the growth of established tumours. Our results
      suggest that the ectopic expression of GITRL in tumour cells enhances anti-tumour
      immunity at peripheral tumour sites. Consequently, the combined use of a GITRL
      tumour vaccine with methods aimed at enhancing the activation of host antigen
      presenting cells in secondary lymphoid tissues may be a promising strategy for
      tumour immunotherapy.

PMID- 19604301
TI  - Inverse relationship between dendritic cell CCR9 expression and maturation state.
AB  - CCR9 has been identified on T cells as a chemokine receptor that directs these
      cells to migrate to the intestine. CCR9 has also been reported on different cell
      types in the intestine, thymus, liver and peripheral blood. Little is reported
      concerning the presence of or functional implications of this chemokine receptor
      on myeloid dendritic cells (DC). In the host, DC encounter a multiplicity of
      antigenic stimuli to which they mount immune responses. In addition to
      intracellular and functional changes on sensing antigen, maturation of DC is
      typically reflected in the up-regulation of costimulatory molecules on DC.
      However, alterations in other surface markers may also be an indicator of DC
      activation. Using bone marrow-propagated DC these studies investigated cellular
      maturation in the presence of microbial stimuli and analyzed the relationship of
      CCR9 expression with DC maturation. Fractionation of DC into CCR9(high) and
      CCR9(low)subsets revealed a distinct ability of each subset to induce division in
      naive CD4(+) T cells. Our results suggest that DC expressing high levels of CCR9
      are less activated/mature than DC expressing low levels of CCR9.

PMID- 19604303
TI  - Induction of allogeneic mixed chimerism by immature dendritic cells and bone
      marrow transplantation leads to prolonged tolerance to major histocompatibility
      complex disparate allografts.
AB  - Mixed chimerism has been shown to lead to prolonged major histocompatibility
      complex (MHC) disparate allograft survival and immune-specific tolerance;
      however, traditional conditioning regimes often involve myeloablation, which may
      pose a significant safety risk. In this study we examined the use of donor
      C57BL/6 (H-2(b)) immature dendritic cells (imDCs) to tolerize the BALB/c (H-2(d))
      recipient to bone marrow transplantation (BMT), allowing the induction of mixed
      chimerism without immunosuppression or myeloablation. We showed that successful
      mismatched bone marrow engraftment can be achieved using imDCs given up to 3 days
      prior to BMT and that mixed chimerism can be established and detected in excess
      of 100 days post-BMT without evidence of graft-versus-host disease. Furthermore,
      we showed that imDCs can suppress lymphocyte proliferation in response to
      mismatched MHC stimulation, leading to increased expression of interleukin (IL)-4
      and IL-10 and decreased expression of IL-2 and interferon-gamma (IFN-gamma). The
      induction of stable chimeras through pre-conditioning of mice with donor imDCs
      followed by BMT led to tolerance, allowing the long-term survival (> 110 days) of
      mismatched cardiac allografts and the prolonged survival of mismatched skin
      allografts without the need for immunosuppression or myeloablation.
      Transplantation with third-party C3H allografts were rapidly rejected in this
      model, suggesting that immune-specific tolerance was achieved. The induction of
      immune-specific tolerance without the need for immunosuppression or myeloablation
      represents a significant advance in transplant immunology and may provide
      clinicians with a plausible alternative in combating organ rejection following
      transplantation.

PMID- 19604305
TI  - Changes in chemokines and chemokine receptor expression on tonsillar B cells upon
      Epstein-Barr virus infection.
AB  - Chemokines and chemokine receptors are likely to play important roles in the
      pathogenesis of Epstein-Barr virus (EBV) -associated disease. The primary EBV
      infection occurs in the oropharynx where the virus infects mainly tonsillar B
      cells. We have previously shown that CXCR4 expression on tonsillar B cells is
      modulated by EBV. Here, CXCR5 and CCR7 expression, which is important for
      migration into lymphoid tissue, was followed for 14 days after EBV infection of
      tonsillar B cells. Early after infection (2 days) there were only minor changes
      in CXCR5 and CCR7 expression. However, at day 7 the expression of CXCR5, as well
      as of CCR7, was decreased and by day 14 these molecules were no longer present at
      the cell surface. Furthermore, EBV infection affects the chemotactic response to
      CXCL13 and CCL21 (the ligands for CXCR5 and CCR7, respectively) with a reduction
      of ligand-induced migration at day 2. Using gene expression profiling, we
      identified an additional set of chemokines and chemokine receptors that were
      changed upon EBV infection in comparison with non-infected tonsillar B cells. In
      particular, messenger RNA expression for CCR9 and the complement receptor C5AR1
      was increased. Both receptors mediate homing to mucosal tissue. The alterations
      of the expression of these molecules may lead to retention of EBV-infected
      tonsillar B cells in the interfollicular region of the tonsil.

PMID- 19604304
TI  - Characterization of cis-regulatory elements conferring mercury-induced
      interleukin-4 gene expression in rat mast cells: a role for signal transducer and
      activator of transcription 6 and TATA box binding sites.
AB  - We have previously shown that oxidative stress is involved in the pathogenesis of
      a mercuric chloride (HgCl(2))-induced, T helper type 2 (Th2)-driven autoimmune
      syndrome in Brown Norway (BN) rats. In the context of the syndrome, the oxidative
      stress-induced mast cell response seems to determine the development of the early
      phase of vasculitis, while oxidative stress-mediated interleukin (IL)-4
      production may contribute to the subsequent Th2-driven autoimmune response.
      However, the molecular basis of IL-4 gene transcription induced by HgCl(2) in
      mast cells remains unknown. In the present study, we dissect the critical
      regulatory mechanisms in the IL-4 gene promoter in the rat mast cell line RBL
      2H3. Immunoprecipitation provided evidence that treatment with HgCl(2) increased
      phosphorylation of signal transducer and activator of transcription 6 (STAT6).
      Transient transfection reporter analyses with a series of 5' end deletions of the
      IL-4 promoter produced evidence that STAT6 and TATA box binding sites are
      important in HgCl(2)-induced IL-4 gene expression. Subsequent elimination of one
      or both sites by site-directed mutagenesis significantly inhibited IL-4 promoter
      activity. Our results provide evidence that STAT6 and TATA box regulatory
      elements play an important role in HgCl(2)-induced IL-4 transcription in rat mast
      cells.

PMID- 19604306
TI  - Identification of three distinct subsets of migrating dendritic cells from oral
      mucosa within the regional lymph nodes.
AB  - To investigate the phenotypic and migrational properties of oral mucosal
      dendritic cells (OMDCs), fluorescein isothiocyanate (FITC) was painted onto mouse
      buccal mucosa and the expression patterns of functional molecules in FITC-bearing
      migrating DCs within the regional lymph nodes (RLNs) were analysed. We found
      three distinct subpopulations of migrating OMDCs within the RLNs: CD11c(hi)
      CD207(-) (F1), CD11c(int/lo) CD207(-) (F2) and CD11c(int/lo) CD207(+) (F3). The
      F1 DCs reached the RLNs earlier (after 24 hr) but diminished immediately.
      Additionally, F1 DCs expressed high levels of CD11b. The F2 DCs migrated
      continuously to the RLNs and maintained the highest ratio of all three fractions.
      The F3 DCs migrated slowly to the RLNs and demonstrated a late peak at 96 hr. In
      addition, F3 DCs showed the highest CD205 expression levels of all three subsets.
      All fractions of migrating OMDCs expressed CD80, CD86 and major
      histocompatibility complex class II at high levels, suggesting that all OMDCs are
      in a mature stage and have the potential for antigen presentation. All migrating
      OMDCs lacked CD8alpha expression. Taken together, our results indicate that the
      lack of CD207 is one factor that identifies submucosal DCs. Both F1 and F2 DCs
      lack CD207; F1 DCs are resident and F2 DCs are newly recruited following FITC
      application. The F3 DCs, which express CD207, are mucosal Langerhans cells that
      migrate later. The identification of OMDC subsets should facilitate further
      studies investigating the functional roles of each fraction.

PMID- 19604307
TI  - Depletion of gammadelta+ T cells increases CD4+ FoxP3 (T regulatory) cell
      response in coxsackievirus B3-induced myocarditis.
AB  - Coxsackievirus B3 (CVB3) causes severe myocarditis in BALB/c mice which depends
      upon CD4(+) T helper type 1 [Th1; i.e. interferon-gamma(+) (IFN-gamma(+))] and
      gammadelta(+) cells. Depleting gammadelta(+) cells using anti-gammadelta antibody
      suppresses myocarditis and CD4(+) IFN-gamma(+) cell numbers in the spleen and
      heart of infected mice while increasing CD4(+) FoxP3(+) cells. Mice deficient in
      gammadelta(+) cells have increased numbers of naive (CD44(lo) CD62L(hi)) and
      fewer effector (CD44(hi) CD62(lo)) memory CD4(+) cells than infected
      gammadelta(+)-cell-sufficient mice. Virus neutralizing antibody titres are not
      significantly different between gammadelta(+) T-cell-sufficient and -deficient
      animals. To confirm that the memory cell response differs in acutely infected
      mice lacking gammadelta(+) cells, CD4(+) cells were purified and adoptively
      transferred into naive recipients, which were rested for 4 weeks then infected
      with CVB3. Recipients given either 0.5 x 10(6) or 1.0 x 10(6) CD4(+) from
      infected donors developed over twice the severity myocarditis and 10-fold less
      cardiac virus titre compared with recipients given equivalent numbers of CD4(+)
      cells from infected and gammadelta(+)-cell-depleted donor animals. Additionally,
      to show that more functionally active T regulatory cells are present in
      gammadelta(+) T-cell-depleted mice, CD4(+) CD25(+) and CD4(+) CD25(-) cells were
      isolated and adoptively transferred into infected recipients. Mice receiving
      CD4(+) CD25(+) cells from gammadelta(+) T-cell-depleted donors developed
      significantly less myocarditis and CD4(+) Th1 cell responses compared with mice
      receiving equal numbers of CD4(+) CD25(+) cells from infected gammadelta(+) T
      cell-sufficient animals. This study shows that gammadelta(+) cells promote CD4(+)
      IFN-gamma(+) acute and memory responses by limiting FoxP3(+) T regulatory cell
      activation.

PMID- 19604308
TI  - Cytolytic mechanisms and T-cell receptor Vbeta usage by ex vivo generated Epstein
      Barr virus-specific cytotoxic T lymphocytes.
AB  - Ex-vivo-generated Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL)
      have been used for cellular adoptive immunotherapy of EBV-associated lymphomas.
      Here we investigated the phenotypes, cytolytic mechanisms, polyfunctionality and
      T-cell receptor (TCR) usage in growing and established CTL, generated by weekly
      stimulation with an EBV-transformed autologous lymphoblastoid cell line (LCL).
      Our results showed that phenotypically mature CTL developed within the first 4
      weeks of culture, with an increase in CD45RO and CD69, and a decrease in CD45RA,
      CD62L, CD27 and CD28 expression. Spectratyping analysis of the variable beta
      chain of the TCR revealed that TCR repertoire remained diverse during the course
      of culture. Cytotoxicity of CTL was significantly inhibited by concanamycin A (P
      < 0.0001) and ethylene glycol-bis tetraacetic acid (P < 0.0001), indicating that
      a calcium and perforin-mediated exocytosis pathway with the release of granzyme B
      was the principal cytotoxic mechanism. The CTL mainly produced interferon-gamma
      (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) upon restimulation with
      autologous LCL, although there were some polyfunctional cells producing IFN-gamma
      and TNF-alpha. Granzyme B, perforin and Fas ligand were detected in CD8(+) and
      CD4(+) cells in all CTL; however, a greater proportion of CD8(+) than CD4(+) T
      cells expressed granzyme B (P < 0.0001) and more granzyme B was detected in
      CD8(+) T cells than in CD4(+) T cells (P = 0.001). This difference was not
      observed with Fas ligand or perforin expression. Our results provide insight into
      the basic characteristics of ex-vivo-generated CTL.

PMID- 19604311
TI  - Immunoglobulin superfamily is conserved but evolved rapidly and is active in the
      silkworm, Bombyx mori.
AB  - Immunoglobulin superfamily (IgSF) proteins are known for their abilities to
      specifically recognize and adhere to cells. In this paper, we predicted the
      presence of 133 IgSF proteins in the silkworm (Bombyx mori) genome. Comparison
      with similar proteins in other model organisms (Caenorhabditis elegans,
      Drosophila melanogaster, Anopheles gambiae, Apis mellifera and Homo sapiens)
      indicated that IgSF proteins are conserved but have rapidly evolved from worms to
      human beings. However, these proteins are well conserved amongst insects.
      Silkworm microarray-based expression data showed tissue expression of 57 IgSF
      genes and microbe-induced differential expression of 37 genes. Based on the
      expression data, we can conclude that the silkworm IgSF is active.

PMID- 19604309
TI  - Signal transducer and activator of transcription 4 limits the development of
      adaptive regulatory T cells.
AB  - T-cell responses to a cytokine milieu instruct the development of multiple
      effector phenotypes. While transforming growth factor-beta(1) (TGF-beta(1))
      inhibits the development of T helper type 1 (Th1) and Th2 cells, we demonstrate
      that like interleukin-6 (IL-6) and IL-4, IL-12 can inhibit the development of TGF
      beta(1)-induced Foxp3-expressing adaptive T regulatory (aTreg) cells. Signal
      transducer and activator of transcription 4 (STAT4) is critical for the response
      to IL-12, although there is a parallel pathway involving T box expressed in T
      cells (T-bet), and cells from mice double-deficient in STAT4 and T-bet are
      refractory to the inhibition of aTreg-cell development by IL-12. While the
      ability of these cytokines to promote Th differentiation may contribute to this
      effect, we observe that culture with IL-12, or other instructive cytokines,
      results in an increase in repressive chromatin modifications at the Foxp3 locus
      that limit STAT5 binding to Foxp3, without observed effects on IL-2 signalling
      pathways. In a model of allergic lung inflammation there are increased
      percentages of Treg cells in the lungs of Stat4(-/-) mice, compared with wild
      type mice, and increases in Treg cells correlate with decreased allergic
      inflammation. Overall, these results suggest an important role for STAT4 in
      regulating Treg-cell development.

PMID- 19604312
TI  - Identification and characterization of antimicrobial peptide, defensin, in the
      taiga tick, Ixodes persulcatus.
AB  - Ixodes persulcatus is the primary vector for human tick-borne diseases in Japan.
      A cDNA library was constructed from whole body homogenates of fed nymphs of I.
      persulcatus. From this library, one cDNA encoding defensin-like antimicrobial
      peptide was identified. The amino-acid sequence showed high similarity to those
      of the defensins of other ticks and arthropods. I. persulcatus defensin mRNA
      transcripts were detected at all life cycle stages of fed ticks and found to be
      predominantly expressed in the midguts of adult female ticks, but not in the
      salivary glands, a finding corroborated by Western blotting analysis. To
      investigate the function of I. persulcatus defensin, we examined its
      antibacterial activity by evaluation of growth of several bacterial strains in
      the presence of the synthetic peptide. The defensin from I. persulcatus markedly
      inhibited the growth of Gram-positive bacteria including Staphylococcus aureus,
      Bacillus subtilis and Corynebacterium renale, but not Gram-negative bacteria
      except Escherichia coli O157. In conclusion, these results suggest that I.
      persulcatus defensin may be playing a significant role in the defence against
      microbes from bloodmeals.

PMID- 19604313
TI  - Stem cells are resistant to TRAIL receptor-mediated apoptosis.
AB  - New therapeutic approaches aim to eradicate tumours by expression of tumouricidal
      proteins in the tumour stroma. One such anti-neoplastic protein is tumour
      necrosis factor-related apoptosis-inducing ligand (TRAIL) because it induces
      apoptosis in cancerous cells, but not in non-transformed cells. Stem cells can
      migrate to, survive and proliferate in tumours. We examined the suitability of
      bone marrow-derived adult mesenchymal stem cells (bmMSC), foetal-MSC and
      umbilical cord matrix stem cells (Wharton's Jelly MSCs) as TRAIL-delivery
      vehicles. Although all MSC types expressed DR4 and/or DR5, none of them were
      sensitive to TRAIL-induced apoptosis. Selective activation of DR4 or DR5 with
      agonistic antibodies or DR5-selective TRAIL-mutant (D269H/E195R) revealed that
      the TRAIL receptors are inactive in MSCs. In fMSC DR5 was not fully inactivated,
      its activity however was minimal in comparison to the colon carcinoma cell,
      Colo205. The intracellular components of the TRAIL-apoptotic pathway, such as pro
      caspase-8 and -9 were also expressed at very low; almost undetectable levels in
      all three MSC types. In conclusion, the MSC species examined are resistant to
      TRAIL and thus can be suitable tools for TRAIL delivery to tumours.

PMID- 19604314
TI  - Repression of the cardiac myosin light chain-2 gene in  skeletal muscle requires
      site-specific association of  antithetic regulator, Nished, and HDACs.
AB  - The transcriptional activation mechanisms that regulate tissue-specific
      expression of cardiac muscle genes have been extensively investigated, but little
      is known of the regulatory events involved in repression of cardiac-specific
      genes in non-cardiac cells. We have previously reported that Nished, a ubiquitous
      transcription factor, interacts with a positive sequence element, the Intron
      Regulatory Element (IRE) as well as a negatively acting element, the Cardiac
      Specific Sequence (CSS), in myosin light chain-2 (MLC2v) gene to promote
      activation and repression of the gene in cardiac and skeletal muscle cells
      respectively. Here, we show that the negative regulation of cardiac MLC2v gene in
      skeletal muscle cells is mediated via the interaction of Nished with histone
      deacetylase (HDAC) co-repressor. Treatment of cells with the HDAC inhibitor,
      Trichostatin A (TSA), alleviates the repressor activity of Nished in a dose
      dependent manner. Co-transfection studies in primary muscle cells in culture and
      in Nished expressing stable skeletal muscle cell line demonstrate that Nished
      down-regulates the cardiac MLC2 gene expression when its association is
      restricted to CSS alone. Chromatin immunoprecipitation data suggest that the CSS
      mediated repression of cardiac MLC2v gene in skeletal muscle cells excludes the
      participation of the positive element IRE despite the presence of an identical
      Nished binding site. Taken together, it appears that the negative control of
      MLC2v transcription is based on a dual mode of regulations, one that affords
      inaccessibility of IRE to Nished and second that promotes the formation of the
      transcription repression complex at the inhibitory CSS site to silence the
      cardiac gene in skeletal muscle cell.

PMID- 19604315
TI  - Activation of epidermal growth factor receptor results in snail protein but not
      mRNA overexpression in endometrial cancer.
AB  - Reduced E-cadherin expression is associated with tumour progression of many
      carcinomas, including endometrial cancers. The transcription factor Snail is
      known as one of the most prominent transcriptional E-cadherin repressors; its
      regulation in cancer tissues, however, still remains unclear. Here, we report
      that activation of epidermal growth factor receptor (EGFR) resulted in
      overexpression of Snail and also identified critical downstream signalling
      molecules. Stimulation of two endometrial carcinoma cell lines with epidermal
      growth factor (EGF) lead to an increase of Snail protein expression. In primary
      human endometrioid endometrial carcinomas Snail protein expression correlated
      with the activated, phosphorylated form of EGFR (Tyr1086) as revealed by
      profiling 24 different signalling proteins using protein lysate microarrays. In
      addition, we observed an inverse correlation between Snail and E-cadherin protein
      levels in these tumours. Most likely, p38 MAPK, PAK1, AKT, ERK1/2 and GSK-3beta
      are involved in the up-regulation of Snail downstream of EGFR. Snail mRNA
      expression did not show a correlation with activated EGFR in these tumours. Taken
      together, profiling of signalling proteins in primary human tissues provided
      strong evidence that EGFR signalling is involved in Snail protein overexpression.

PMID- 19604316
TI  - Signal transduction of MCP-1 expression induced by pancreatitis-associated
      ascitic fluid in pancreatic acinar cells.
AB  - Pancreatitis-associated ascitic fluid (PAAF) is known to contribute to the
      progression of acute pancreatitis (AP). We have investigated the capability of
      PAAF to activate the expression of MCP-1 in pancreatic acinar cells and the
      involvement of MAPK, NF-kappaB and STAT3 as downstream signalling transduction
      pathways. The actions of dexamethasone (Dx) and N-acetylcysteine (NAC) on the
      PAAF's acinar effects have also been evaluated. Acinar cells were incubated for 1
      hr with PAAF collected from rats with severe AP induced by sodium taurocholate in
      the absence or presence of Dx (10(-7) M) or NAC (30 mM). MCP-1 mRNA expression,
      phospho-p38-MAPK, IkappaB alpha, nuclear p65 levels and nuclear translocation of
      STAT3 were analysed. In response to PAAF, overexpression of MCP-1,
      phosphorylation of p38-MAPK, degradation of IkappaB alpha and increases in p65
      nuclear levels and STAT3 activity were found in acinar cells. PAAF-mediated MCP-1
      up-regulation was completely suppressed by Dx and NAC. MAPK activation was only
      inhibited by NAC, NF-kappaB activation was repressed by Dx and NAC, and STAT3
      pathway was strongly blocked by Dx and significantly reduced by NAC. In
      conclusion, acinar cells were activated by PAAF to produce MCP-1, mainly via NF
      kappaB and STAT3 pathways. Both downstream pathways were targeted by Dx and NAC
      to repress the PAAF-mediated acinar MCP-1 up-regulation.

PMID- 19604317
TI  - A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a
      wide range of HLA specificities.
AB  - Human cytomegalovirus (HCMV) can cause life-threatening disease in infected
      hosts. Immunization with human leukocyte antigen (HLA)-restricted immunodominant
      synthetic peptides and adoptive transfer of epitope-specific T cells have been
      envisaged to generate or boost HCMV-specific cellular immunity, thereby
      preventing HCMV infection or reactivation. However, induction or expansion of T
      cells effective against HCMV are limited by the need of utilizing peptides with
      defined HLA restrictions. We took advantage of a combination of seven predictive
      algorithms to identify immunogenic peptides of potential use in the prevention or
      treatment of HCMV infection or reactivation. Here we describe a pp65-derived
      peptide (pp65(340-355), RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar
      features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in
      both CD4(+) and CD8(+) T cells, restricted by a wide range of HLA class I and II
      determinants. Second, RQY-16mer is able to induce an unusually wide range of
      effector functions in CD4(+) T cells, including proliferation, killing of
      autologous HCMV-infected target cells and cytokine production. Third, and most
      importantly, the RQY-16mer is able to stimulate CD4(+) and CD8(+) T-cell
      responses in pharmacologically immunosuppressed patients. These data suggest that
      a single reagent might qualify as synthetic immunogen for potentially large
      populations exposed to HCMV infection or reactivation.

PMID- 19604318
TI  - Short-term treatment of a resilient appliance in TMD pain patients: a randomized
      controlled trial.
AB  - To investigate the short-term efficacy of a resilient appliance in patients with
      temporomandibular disorders (TMD) suffering from pain, a randomized, controlled
      trial was performed in 80 recruited TMD pain patients. They were randomly
      allocated to one of two groups: treatment with a resilient appliance or treatment
      with a hard, palatal, non-occluding appliance. The primary treatment outcome
      measure was judged positive when patients' TMD pain at worst, according to the
      Visual Analog Scale (VAS), decreased by at least 30%. One additional treatment
      outcome was reduction of characteristic pain intensity. Number needed to treat
      was measured on the basis of primary treatment outcome at 10 weeks. At baseline,
      patient characteristics and TMD pain did not differ between the groups. There
      were no significant differences between groups regarding a 30% reduction in VAS
      reported TMD pain at worst at 10 weeks' follow-up; 61% in the treatment group and
      46% in the control group. After 6 and 10 weeks of treatment, CPI decreased in
      both groups. Number needed to treat was 9.1 for both the resilient and the
      control appliance therapy during 10 weeks. There was no statistically significant
      difference between the resilient appliance and the non-occluding control
      appliance in reducing TMD pain from a short-term perspective.

PMID- 19604319
TI  - Effect of hypnosis on oral function and psychological factors in
      temporomandibular disorders patients.
AB  - This study investigated the effect of hypnosis in patients with temporomandibular
      disorders (TMD) with focus on oral function and psychological outcomes. Forty
      women (mean age +/- s.d.: 38.6 +/- 10.8 years) suffering from TMD (mean duration
      11.9 +/- 9.9 years) were randomized to four individual 1-hour sessions of either
      hypnotic intervention or a control condition of simple relaxation. Pain intensity
      was assessed three times daily on a 0-10 Numerical Rating Scale. Additional
      outcomes were TMD-associated symptoms assessed by the Research Diagnostic
      Criteria examination form and questionnaire, psychological symptoms (Symptom
      Check List 60), pain coping strategies (Coping Strategies Questionnaire), sleep
      difficulties (Pittsburgh Sleep Quality Index) and use of analgesics. Data were
      analyzed with between-groups within-subjects anovas. The hypnosis group
      significantly reduced the daily NRS pain scores from 4.5 +/- 2.1 at baseline to
      2.9 +/- 2.4 after treatment (P < 0.001) compared to the control group where no
      significant changes were found (4.2 +/- 1.4 to 3.9 +/- 1.5) (P = 0.733). Number
      needed to treat for a 50% pain reduction was 4.0. The hypnosis group also
      increased use of the coping strategy 'reinterpreting pain sensations' from 5.2 +/
      6.9 to 10.3 +/- 6.8 (P < 0.001). Both groups exhibited significant reductions in
      the number of painful muscle palpation sites and pain on palpation (P < 0.004),
      in number of awakenings due to pain (P < 0.006), and in somatization, obsessive
      compulsive symptoms and anxiety (P < 0.004). Hypnosis thus appears to effectively
      reduce some aspects of complex TMD pain.

PMID- 19604320
TI  - Dental health state utility values associated with tooth loss in two contrasting
      cultures.
AB  - The study aimed to assess the value placed on oral health states by measuring the
      utility of mouths in which teeth had been lost and to explore variations in
      utility values within and between two contrasting cultures, UK and Iran. One
      hundred and fifty eight patients, 84 from UK and 74 from Iran, were recruited
      from clinics at University-based faculties of dentistry. All had experienced
      tooth loss and had restored or unrestored dental spaces. They were presented with
      19 different scenarios of mouths with missing teeth. Fourteen involved the loss
      of one tooth and five involved shortened dental arches (SDAs) with varying
      numbers of missing posterior teeth. Each written description was accompanied by a
      verbal explanation and digital pictures of mouth models. Participants were asked
      to indicate on a standardized Visual Analogue Scale how they would value the
      health of their mouth if they had lost the tooth/teeth described and the
      resulting space was left unrestored. With a utility value of 0.0 representing the
      worst possible health state for a mouth and 1.0 representing the best, the mouth
      with the upper central incisor missing attracted the lowest utility value in both
      samples (UK = 0.16; Iran = 0.06), while the one with a missing upper second molar
      the highest utility values (0.42, 0.39 respectively). In both countries the
      utility value increased as the tooth in the scenario moved from the anterior
      towards the posterior aspect of the mouth. There were significant differences in
      utility values between UK and Iranian samples for four scenarios all involving
      the loss of anterior teeth. These differences remained after controlling for
      gender, age and the state of the dentition. With respect to the SDA scenarios, a
      mouth with a SDA with only the second molar teeth missing in all quadrants
      attracted the highest utility values, while a mouth with an extreme SDA with both
      missing molar and premolar teeth in all quadrants attracted the lowest utility
      values. The study provided further evidence of the validity of the scaling
      approach to utility measurement in mouths with missing teeth. Some cross-cultural
      variations in values were observed but these should be viewed with due caution
      because the magnitude of the differences was small.

PMID- 19604324
TI  - Behavioral and psychological symptoms of dementia and medical treatment.

PMID- 19604325
TI  - Clinical effects of high oral dose of donepezil for patients with Alzheimer's
      disease in Japan.
AB  - BACKGROUND: Donepezil 10 mg/day gained approval in Japan in August 2007 for the
      treatment of cognitive dysfunction in advanced Alzheimer's disease. METHODS: We
      evaluated the efficacy and adverse effects of donepezil when the dose was
      increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease.
      Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and
      mini-mental state examination at the day before starting, and at 4, 8 and 24
      weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4
      was also investigated. RESULTS: The Revised Hasegawa Dementia Scale and mini
      mental state examination scores were not statistically significantly different at
      any time after starting donepezil 10 mg/day. It can be anticipated that donepezil
      10 mg/day will especially inhibit deterioration of cognitive function in advanced
      Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the
      rate of 40% or higher recorded during previous clinical trials. CONCLUSIONS: The
      progression of cognitive dysfunction could be inhibited by increasing the dose of
      donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day
      might lead to fewer adverse events when the dose is increased to 10 mg/day.

PMID- 19604326
TI  - Depression associated with dementia with Lewy bodies (DLB) and the effect of
      somatotherapy.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) is a common type of dementia. It is
      difficult to make an initial diagnosis of DLB because of a variety of early
      symptoms, including psychosis-like and depressive states. In this study, we
      examined the characteristic depressive symptoms of the prestage of DLB and the
      efficacy and safety of somatotherapy for depression accompanying DLB. METHODS:
      Subjects in the study were 167 consecutive clinical cases aged 50 years or more,
      hospitalized at Tsukuba University Hospital from December 2002 to September 2007.
      At the time of admission, patients were diagnosed with certain types of mood
      disorders according to the Diagnostic and Statistical Manual of Mental Disorders
      Fourth Edition Text Revision. For each subject, a series of neuropsychological
      tests, along with a standard psychiatric and neurological assessment and
      biological examinations, were conducted. Using the data from these exams, we
      diagnosed probable and possible DLB according to the criteria for dementia with
      Lewy bodies established by McKeith et al. 1 We compared patients' depressive
      symptoms according to the Hamilton Depression Scale, and distinguished between
      patients with depression associated with DLB and those with other mood disorders.
      2 We also examined the efficacy and safety of somatotherapy (electroconvulsive
      therapy (ECT) and transcranial magnetic stimulation (TMS)) for patients with drug
      therapy-resistant depression associated with DLB. RESULTS: 1 The characteristic
      symptoms of patients with DLB were classified into two groups: psychotic and non
      psychotic. The former consisted of patients with states such as delusion and
      agitation, and the latter included patients exhibiting psychomotor retardation,
      loss of insight and hypochondriasis. 2 Eight DLB patients with therapy-resistant
      depression underwent ECT. After ECT, significant improvement was observed, with
      no remarkable safety hazards. Six patients with drug therapy-resistant DLB
      underwent TMS. TMS appears to be an effective, safe remedy for this kind of
      patient. CONCLUSIONS: A total of 13.8% of patients came to be re-diagnosed as
      having DLB as a consequence of a thorough examination after admission. Patients
      with depression associated with DLB were classified into psychotic and non
      psychotic clusters. ECT and TMS are effective and safe therapeutic tools for drug
      therapy-resistant depression observed in DLB patients.

PMID- 19604327
TI  - Suicide among the elderly in mainland China.
AB  - Suicide in mainland China shows unique demographic patterns with age: the over-65
      age group has the highest rate of completed suicide, reaching 44.3-200 per
      100,000, which is four to five times higher than the Chinese general population.
      Rural suicide rates among the elderly are three to five times higher than the
      urban rates. The gender ratio of suicide in the elderly shows a reversal to those
      younger than 60 years of age in China. In addition, suicide methods and causes
      are different from those in Western countries. In the present paper, the profile
      of suicide among the elderly in China is delineated, including the prevalence,
      characteristics, underlying reasons and measures of preventing it.

PMID- 19604328
TI  - What is 'early onset dementia'?
AB  - There are two types of dementia with early onset: (i) presenile dementias; and
      (ii) senile dementias with early onset. Most patients who develop dementia before
      65 years of age have Alzheimer's disease (AD). The remainder are likely to have
      vascular dementia (VaD), frontotemporal dementia, head injury, alcohol
      intoxication, or metabolic disorder. Presenile dementias, caused by
      frontotemporal lobar degeneration, progressive supranuclear palsy, and
      corticobasal degeneration, usually occur in patients of presenile and are rarely
      seen in patients of senile age. Although the factors responsible for the
      accelerated onset of the illness are not fully known, genetic abnormalities
      appear to be important in some types of presenile dementia, such as
      frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely,
      senile dementias such as sporadic AD and VaD commonly occur in patients of senile
      age. These disorders may also occur in patients of presenile age, although less
      frequently. Alzheimer's disease was originally classified as a 'presenile
      dementia'. Since the 1980s, 'senile dementia of Alzheimer type' (SDAT) and
      'Alzheimer's disease' have been considered to belong to the same pathological
      entity and both are now known as 'dementia of Alzheimer's type (DAT)' or merely
      'Alzheimer's disease'. Rapid progression of cognitive impairment with
      neuropsychological syndromes and neurological symptoms has been considered a
      characteristic of early onset AD. However, recently, neurological symptoms such
      as spastic paraparesis, seizures, and myoclonic convulsions have been reported to
      occur infrequently in early onset AD, although language problems and visuospatial
      dysfunctions are common. There are at least three dominant genes that have been
      identified in cases of familial Alzheimer's disease with early onset, namely the
      amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and
      presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors
      contributing to the earlier onset of the illness. It is also important to
      investigate the pathophysiological mechanism in relation to genetic
      abnormalities, environmental factors, physical illnesses, and metabolic
      disturbances to understand the processes underlying the development of dementia
      with early onset.

PMID- 19604329
TI  - Pathogenesis and symptomatology of hallucinations (delusions) of organic brain
      disorder and schizophrenia.
AB  - In this review article, in order to explore the mechanisms underlying the
      hallucinations/delusions of schizophrenia, we discuss the contribution of the
      following four questions: (i) can an understanding of dreams contribute to our
      understanding of the genesis of halluciations and/or delusions; (ii) are the
      mechanisms underlying psychotropic drug-induced psychoses the same as those
      underlying the hallucinations and/or delusions in schizophrenia; (iii) does
      disturbed consciousness contribute to the manifestation of psychotic features;
      and (iv) are the psychoses caused by organic brain disorders any different to the
      hallucinations and/or delusions seen in schizophrenia? We conclude that there is
      a strong association between drug-induced hallucinations or hallucinations
      associated with organic brain disorders and simple hallucinosis or fluctuations
      in arousal level. Because intermediate configurations and/or cross-staining
      phenomena exist for hallucinations and delusions, especially in schizophrenic
      disorders, it is difficult to isolate the hallucinations and to recognize them as
      being abnormal experiences.

PMID- 19604330
TI  - Neuroimaging studies in patients with Charles Bonnet Syndrome.
AB  - Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent
      visual hallucinations in psychologically normal people, and is often associated
      with eye pathology. Many psychiatrists have taken an interest in CBS because this
      syndrome could provide clues to the mechanisms underlying visual hallucinations.
      In the present paper, we review previous neuroimaging studies in patients with
      CBS and summarize the results of these studies. There could be a fundamental
      dysfunction in the primary and secondary visual cortices in some patients with
      CBS, and transient cortical activation occurs in the inferior lateral temporal
      cortex during the appearance of visual hallucinations in CBS patients. External
      visual stimuli are perceived in the retina and are transmitted to the primary
      visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to
      the secondary visual cortex (BA 18) and then to the visual association cortices
      (BA 19 and BA 37). In general, our perception of external visual stimuli normally
      has an inhibitory effect on the endogenous activation of the visual cortex.
      Visual loss due to certain conditions, of which eye pathology is the most
      commonly postulated in CBS patients, produces a state of sensory deprivation that
      releases the visual cortex from regulation by external stimuli, resulting in
      visual hallucinations (cortical release phenomenon). The results of previous
      neuroimaging studies suggest that the cortical release phenomenon hypothesis for
      the occurrence of visual hallucinations in patients with CBS is plausible. In
      addition, the results indicate that not only eye pathology, but also dysfunction
      in the primary and secondary visual cortices could result in deprivation of
      external visual stimuli.

PMID- 19604331
TI  - Neuropsychological profile of dementia with Lewy bodies.
AB  - Dementia with Lewy bodies (DLB) accounts for 10-25% of all dementia cases in
      clinical populations and is considered to be the second most common degenerative
      dementia in elderly people after Alzheimer's disease (AD). Dementia with Lewy
      bodies is characterized by the presence of cognitive, psychiatric, and motor
      symptoms. Although the neuropsychological profiles of patients with DLB often
      differ from those of patients with AD, the diagnostic sensitivity, specificity,
      and predictive values of these profiles remain largely unknown. The present paper
      reviews the neuropsychological profiling of DLB and attempts the
      neuropsychological differentiation of DLB from AD.

PMID- 19604332
TI  - Frontotemporal lobar degeneration and dementia with Lewy bodies:
      clinicopathological issues associated with antemortem diagnosis.
AB  - Currently, the clinical diagnostic criteria of frontotemporal lobar degeneration
      (FTLD) and dementia with Lewy bodies (DLB) are well known to neurologists and
      psychiatrists. However, the accuracy of the clinical diagnosis of these diseases
      in autopsy series is not always adequate. For example, FTLD is a syndrome rather
      than a clinicopathological disease entity that is comprised of various
      pathological substrates, including Pick's disease, FTLD with microtubule
      associated protein tau gene mutation, FTLD with tau-negative ubiquitin-positive
      inclusions (FTLD-U), FTLD-U with progranulin gene mutation, corticobasal
      degeneration, basophilic inclusion body disease, and neuronal intermediate
      filament inclusion disease. Whether these underlying pathologies can be
      identified clinically is one of the greatest interests in neuropathological
      research. The pathophysiological relationship between Lewy pathology and
      Alzheimer pathology in DLB is explored with interest because it may be associated
      with the accuracy of clinical diagnoses. For example, although Lewy pathology may
      progress from the brain stem nuclei to the cerebral cortex in Parkinson's
      disease, recent studies have demonstrated that the progression pattern in DLB is
      not always identical to that in Parkinson's disease. It is also considered that
      the progression pattern of Lewy pathology correlates with the evolution of
      clinical symptoms and that the progression pattern of Lewy pathology may be
      altered when Alzheimer pathology coexists. In the present paper, the
      clinicopathological features of two demented cases are presented, and some
      pathological issues associated with the clinical diagnosis of FTLD and DLB are
      discussed.

PMID- 19604333
TI  - Novel therapeutic strategies for neurodegenerative disease.
AB  - The activity of protein phosphatase 2A (PP2A) is compromised and believed to be
      the cause of the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD)
      brain. Activity of PP2A is regulated by two endogeneous inhibitor proteins,
      called as I(1)(PP2A) and I(2)(PP2A). Previously, we reported that: (i) I(1)(PP2A)
      and I(2)(PP2A) are upregulated with cleavage of I(2)(PP2A) holoprotein and
      translocation of its amino terminal fragment from the nucleus to the cytoplasm in
      neuronal cells in AD brains; and (ii) translocated I(2)(PP2A) colocalized not
      only with the PP2A catalytic subunit, but also with phosphorylated tau in
      neuronal cytoplasm. Furthermore, according to preliminary data, the cleavage site
      of I(2)(PP2A) is located between amino acids 175 and 176 of the I(2)(PP2A)
      sequence. Because the sequence from amino acids 168 to 181 on I(2)(PP2A)
      presumably functions as a nuclear localization signal (NLS), inhibition of break
      down of the NLS in I(2)(PP2A) is expected to be a novel therapeutic target for
      the treatment of Alzheimer's disease.

PMID- 19604334
TI  - Clinical manifestations of cataracts in small breed dogs.
AB  - OBJECTIVE: To determine the incidence, etiology, and concurrent ophthalmic
      findings in small breed dogs that presented with cataracts. ANIMAL STUDIED: Five
      hundred and sixty-one small breed dogs (942 eyes) were presented to the
      Veterinary Medical Teaching Hospital of Seoul National University between July
      2002 and December 2007 with cataract. PROCEDURE: The medical records of small
      breed dogs with cataract were reviewed. The reason for presentation, cataract
      duration, bilaterality, breed, gender, age, vision, etiology, stage of cataract
      development, concurrent ophthalmic findings, IOP, ocular ultrasonography
      findings, and scotopic electroretinography (ERG) findings were investigated.
      RESULTS: The most frequently presented breeds were the Miniature/Toy Poodle (n =
      112, 20.0%), Yorkshire Terrier (n = 110, 19.6%), and Shih Tzu (n = 95, 16.9%).
      The Miniature/Toy Poodle showed a significantly higher odds ratio for cataract
      formation (2.6). The proportion of female cataract patients was significantly
      higher than that of male cataract patients in the overall population (P < 0.05).
      The Miniature/Toy Poodles had significantly higher numbers of females affected
      with cataract (P < 0.01). The mean age for cataract formation was 8.3 +/- 3.9
      years. The mean age at onset in the Miniature/Toy Poodle and Yorkshire Terrier
      was significantly higher, whereas that in the Miniature Schnauzer group was
      significantly lower (P < 0.0001). Clinical signs related to lens induced uveitis
      had a tendency to increase with cataract progression (P < 0.05). There were no
      significant differences in the b-wave amplitude for mixed rod cone response by
      stage (P = 0.137). CONCLUSIONS: Small breed dogs with cataracts had
      characteristics with regard to age of onset and gender distribution, depending on
      the breed.

PMID- 19604335
TI  - Conjunctival effects of canine distemper virus-induced keratoconjunctivitis
      sicca.
AB  - OBJECTIVE: This study compared the histopathology of canine distemper virus (CDV)
      induced keratoconjunctivitis sicca (KCS) to non-infectious KCS in conjunctival
      tissues. ANIMALS STUDIED: Forty mongrel dogs were assigned to three distinct
      groups: (i) non-infectious KCS (G1, n = 10), (ii) CDV-induced KCS (G2, n = 20),
      and (iii) healthy animals without any ocular alterations (G3, n = 10). PROCEDURE:
      IgG titers and physical and ophthalmic examinations (e.g. Schirmer tear test
      [STT], tonometry, biomicroscopy, indirect biomicroscopy, and fluorescein test)
      were performed on all dogs. Conjunctival biopsies were collected and examined
      microscopically. RESULTS: Non-infectious and CDV-induced KCS demonstrated similar
      histopathological changes. Both types of KCS correlated with low STT,
      conjunctival hyperemia, mucopurulent ocular discharge, predominant
      lymphoplasmacytic infiltration, and acantholysis and keratinization of the ocular
      surface. G1 had lower conjunctival goblet cell counts than G3. Inclusion bodies
      were sporadically found in conjunctival samples of dogs from G2. The severity of
      ocular lesions in G1 and G2 did not correlate with the histopathological
      findings. CONCLUSIONS: Dogs with non-infectious and CDV-induced KCS had very
      similar conjunctival histopathology. Our findings suggest that the
      pathophysiology of CDV-induced KCS is likely to be the same as non-infectious
      KCS, that is, a result of lacrimal deficiency and inflammation of the ocular
      surface.

PMID- 19604336
TI  - Antimicrobial susceptibility of Staphylococci isolated from naturally occurring
      canine external ocular diseases.
AB  - OBJECTIVE: The purpose of this study was to describe the species distribution and
      antimicrobial susceptibility patterns of Staphylococci isolated from naturally
      occurring canine ocular diseases. SAMPLES AND PROCEDURES: Samples obtained from
      68 dogs with signs of external eye disease were processed for isolation of
      bacteria of the genus Staphylococcus sp. Isolates were identified by biochemical
      reactions and tested for susceptibility to 11 antimicrobials of six classes.
      RESULTS: Forty (58.8%) samples yielded Staphylococcus sp. in pure culture.
      Coagulase-positive Staphylococci were most common and Staphylococcus intermedius
      was the most frequent (45%) species, followed by S. aureus (22.5%) and the
      coagulase-negative species S. epidermidis (20%), and S. simulans (12.5%).
      Resistance to at least one drug was observed in 92.5% of the isolates, and
      multidrug resistance was a common finding (72.5%). The most effective drugs
      against Staphylococcus strains isolated from extra-ocular canine ocular diseases
      were ceftiofur and cefalexin. CONCLUSION: This study highlights the presence of
      Staphylococcus sp. genus in naturally occurring extra-ocular canine ocular
      disease and the emergence of resistant strains to common antimicrobial drugs. It
      also emphasizes the need for bacterial culture with species identification and
      susceptibility testing in order to choose the appropriate antimicrobial therapy.

PMID- 19604337
TI  - Feline entropion: a case series of 50 affected animals (2003-2008).
AB  - AIM: To evaluate the signalment, clinical signs, and etiopathogenesis of
      entropion in 50 cats. METHODS: Signalment and history of 50 cases of entropion in
      cats presented to a referral ophthalmology clinic. Animals were examined with
      direct and indirect ophthalmoscopy and slit-lamp biomicroscopy. Animals were
      treated surgically with a Hotz-Celsus procedure and results of surgery were
      evaluated between 4 and 22 weeks. RESULTS: Sixteen cats were young (mean age 4.1
      +/- 3.6 years) with pre-existing irritative ocular surface conditions such as
      conjunctivitis, corneal ulceration or sequestrum. Twenty-six cats were relatively
      older (mean age 11.3 +/- 2.2 years) with involutional entropion with or without
      enophthalmos, presumed to result from a reduction in orbital tissue. Five cats
      were Persians with entropion associated with brachycephalic facial anatomy,
      whereas three were entire young adult male Maine Coones with in-turning
      associated with excessive facial 'jowl' tissue. Surgical treatment was curative
      in the majority of cases after one surgery although an increased amount of eyelid
      tissue was required to be removed for correction compared with similar surgery in
      the dog. DISCUSSION: This study has shown that entropion in cats may be caused in
      young animals as a result of continued blepharospasm related to irritative causes
      such as conjunctivitis or corneal ulceration or in older animals with lid laxity
      or globe enophthalmos. Lid in-turning was also seen in Persian and Maine Coone
      breeds.

PMID- 19604338
TI  - Low-hemorrhage-risk surgical approach to expose the optic nerve in rabbits
      without bony removal and rectus resection.
AB  - OBJECTIVE: A low-hemorrhage-risk surgical approach to expose the optic nerve (ON)
      in rabbits through the orbital process of the frontal bone without removal of the
      bony orbit and resection of the rectus muscle was explored and assessed in this
      study. This approach will be used to investigate a new visual prosthesis that
      requires intraorbital ON stimulation with penetrating electrodes. Animals Chinese
      Albino rabbits (n = 10). METHODS: Rabbits were classified into a surgery and a
      control group (five in each). In the surgery group, the ON exposure was explored
      by the newly proposed surgical approach. Surgical time, blood loss, visually
      evoked potentials (VEP) at four different scheduled time points, and H&E-stained
      histology of the ON at one month after surgery were recorded and analyzed to
      assess the ease and safety of the approach. RESULTS: The average surgical time
      for the ON exposure was 16.40 +/- 1.14 min with average blood loss of 0.52 +/-
      0.08 mL. Within the one-month follow-up, the ON exhibited a naturally reversible
      conduction change in terms of VEP amplitude. Histological examination of the ON
      was unremarkable. A postoperative mild ptosis of the surgical eye resolved within
      one month after surgery. CONCLUSION: The ease and safety of this new surgical
      approach allowed it to be easily used by non-expert operators and widely applied
      in rabbit experiments for various research purposes requiring exposure of the ON.

PMID- 19604339
TI  - The cornea of Guinea pig: structural and functional studies.
AB  - OBJECTIVE: To describe the functional and structural characteristics of the
      cornea in healthy Guinea pigs. ANIMALS STUDIED: Healthy male and female pigmented
      and albino Guinea pigs (Caviaporcellus) aged 3-5 months old were used.
      PROCEDURES: The animals' corneas underwent different in vivo studies including:
      slit-lamp biomicroscopy, fluorescein staining (FS), break-up time test (BUT),
      confocal microscopy and pachymetry. The corneas were also studied
      histopathologically with light microscopy, immunohistochemistry and transmission
      electron microscopy. RESULTS: No significant differences were found between
      pigmented and albino animals, male and female, OD and OS in any study performed.
      The differences on corneal thickness values were not significant among central
      (227.85 +/- 14.09 microm) and upper and temporal peripheral regions (226.60 +/-
      12.50 and 225.70 +/- 14.40 microm, respectively). All histological studies
      performed permitted identification and precise description of the different
      corneal structures in Guinea pigs: the stratified epithelium (45.52 +/- 5.26
      microm), Bowman's layer (2.23 +/- 0.38 microm), stroma (163.69 +/- 4.90 microm),
      Descemet's membrane (3.96 +/- 0.46 microm) and the endothelium (5.09 +/- 0.71
      microm). Combining results from all eyes mean and SD from corneal BUT values was
      4.98 +/- 1.67 s. Corneas often showed discrete superficial erosions being the FS
      positive in both eyes from all the animals. CONCLUSION: This study provides a
      detailed in vivo and postfixed histological description of the Guinea pig's
      cornea and information about the physiological tests.

PMID- 19604340
TI  - Outbreak of ocular disease associated with naturally-acquired canine herpesvirus
      1 infection in a closed domestic dog colony.
AB  - OBJECTIVE: To describe clinical and virological findings of an outbreak of ocular
      disease attributed to naturally-acquired primary canine herpesvirus-1 (CHV-1)
      infection in a closed domestic dog colony. ANIMALS STUDIED: Twenty-seven 10- to
      16-week-old laboratory Beagles. PROCEDURE: Complete ophthalmic examinations were
      performed and ocular samples collected for CHV-1 polymerase chain reaction and
      virus isolation. RESULTS: The prevalence of ocular morbidity was 100% in examined
      dogs. Lesions were restricted to the ocular surface and included bilateral
      conjunctivitis (100% of dogs); punctate, dendritic, or geographic ulcerative
      keratitis (26% of dogs); and non-ulcerative keratitis (19% of dogs). Conjunctival
      petechiae were detected in 22% of dogs. Punctate and dendritic corneal ulcers
      were frequently organized into discrete groups or linear arrangements. Non
      ulcerative keratitis appeared clinically as a perilimbal ring of superficial
      corneal vascularization and leukocyte infiltration. CHV-1 was detected in ocular
      samples by polymerase chain reaction or virus isolation in all dogs sampled.
      CONCLUSIONS: In susceptible populations of domestic dogs, CHV-1 may be associated
      with outbreaks of highly contagious ocular infection in the absence of concurrent
      overt systemic disease. This naturally-acquired outbreak of CHV-1 infection
      provides an opportunity to report the spectrum and prevalence of ocular lesions
      associated with primary ocular CHV-1 infection in dogs. Conjunctivitis was the
      most frequent ocular lesion detected. Ulcerative and non-ulcerative keratitis
      were less prevalent and of variable clinical appearance. Dendritic ulcerative
      keratitis, a classic and relatively specific ocular lesion associated with
      alphaherpesvirus infection, was detected in < 20% of dogs.

PMID- 19604341
TI  - Ligneous conjunctivitis in a plasminogen-deficient dog: clinical management and 2
      year follow-up.
AB  - A 1-year-old-female Yorkshire Terrier was referred to the Veterinary Teaching
      Hospital of the Autonomous University of Barcelona (VTH-UAB) (Spain) with a 6
      month history of unilateral chronic proliferative conjunctivitis and intermittent
      vomiting and cough. Several medical and surgical treatment efforts to manage
      conjunctival lesions had resulted in no improvement of the clinical signs.
      Complete general and ophthalmic examinations revealed several proliferative 'wood
      like' masses in the conjunctiva, oral cavity and an interscapular subcutaneous
      nodule. Conjunctival and buccal biopsies were performed as diagnostic procedures.
      A diagnosis of ligneous conjunctivitis was made on the basis of histopathology
      findings and clinical presentation. The only biochemical abnormalities found were
      severe proteinuria and low plasminogen activity in plasma. No other analytical
      abnormalities were observed. Topical treatment with heparin and anti-inflammatory
      and immunosuppressive drugs have controlled the ophthalmological clinical signs.
      To our knowledge, this is the first case report of a dog with plasminogen
      deficiency and ligneous conjunctivitis with a long survival period and 2-year
      follow-up.

PMID- 19604342
TI  - Metastatic intraocular chondrosarcoma in a dog.
AB  - Chondrosarcoma accounts for about 10% of all canine bone tumors and is the second
      most common primary bone tumor in dogs. In veterinary medicine, chondrosarcomas
      are classified as skeletal and extraskeletal. Extraskeletal chondrosarcomas are
      mesenchymal neoplasms of soft tissues and visceral organs that produce neoplastic
      chondrocytes in a fibrillary matrix. There is no involvement of bone or
      periosteal tissues in extraskeletal chondrosarcomas. The aim of this report is to
      describe the first case of a metastatic intraocular extraskeletal chondrosarcoma
      in a dog.

PMID- 19604343
TI  - Surgical removal of a dermoid cyst from the bony part of the nasolacrimal duct in
      a Scottish highland cattle heifer.
AB  - The ophthalmologic, radiologic and surgical findings of a 2-year-old Scottish
      Highland Cattle heifer with a dermoid cyst within the bony part of the
      nasolacrimal duct and the successful treatment are presented.

PMID- 19604344
TI  - Extra-adrenal paraganglioma of the equine orbit: six cases.
AB  - At The Ohio State University from 1994-2006 six of seven horses evaluated for
      primary orbital disease were diagnosed with extra-adrenal paraganglioma (EAPG).
      The horses ranged in age from 14 to 24 years, with a mean of 16.8 years. Duration
      of clinical signs was 1.5 years to 5 years, with a mean of 2.8 years. Clinical
      signs varied, but all six had non-painful exophthalmus of the right eye. Five
      horses had complete ocular exams reported; three of five had decreased to absent
      vision, two of five had pale optic nerves, and in three of five, difficulty of
      retropulsion of the globe was noted. Diagnostic tests performed included complete
      blood count, serum profile, radiography, ultrasound, computed tomography, true
      cut biopsy, ocular examination, guttural pouch endoscopy, oral examination, and
      physical examination. Expulsive hemorrhage during orbital exenteration occurred
      in all horses. In five of six cases, tumor extension through the orbital foramen
      was apparent intra-operatively. Histopathologic appearance of all surgically
      removed tissues consisted of sheets of polygonal cells with abundant lightly
      granular cytoplasm, round nuclei with vesicular chromatin, and rare mitoses.
      Neoplastic cells were arranged into small groups separated by a fine
      fibrovascular stroma. All six cases were chromagranin positive on
      immunohistochemical staining. Follow-up ranged from six months to six years, with
      a mean of two years. Four of the five horses that recovered from surgery had no
      apparent tumor recurrence in 6-48 months.

PMID- 19604345
TI  - Immunohistochemical detection of NOD1 and NOD2 in the healthy murine and canine
      eye.
AB  - The innate immune system provides the immediate defense against pathogens. NOD1
      and NOD2 proteins are intracytoplasmic signaling receptors of the innate immune
      system and recognize conserved microbial molecular structures. The aim of this
      study was to analyze the expression of NOD1 and NOD2 proteins in healthy mouse
      and dog eyes using immunohistochemistry on formalin-fixed, paraffin-embedded
      globes. In both the mouse and dog globes, a strong immunosignal for NOD1 and NOD2
      was present within corneal epithelium, corneal endothelium and conjunctival
      epithelium. Scattered cells in the conjunctival substantia propria displayed
      moderate immunopositivity for NOD1 and NOD2. Additionally, in dog eyes,
      nonpigmented iridal epithelium was immunopositive for NOD1 and NOD2. No other
      examined ocular tissues were immunopositive for NOD1 or NOD2. To the best of the
      authors' knowledge, this is the first description of an immunohistochemical study
      on NOD1 and NOD2 expression in healthy mouse and dog eyes. Since signaling
      molecules of the innate immune system mediate pro-inflammatory responses in
      numerous organs, they likely also contribute to the pathogenesis of ocular
      inflammation.

PMID- 19604347
TI  - Mesenteric rheumatoid nodules masquerading as an intra-abdominal malignancy: a
      case report and review of the literature.
AB  - BACKGROUND: Rheumatoid nodules are the most common extra-articular findings in
      patients with rheumatoid arthritis. They occur most commonly at pressure points
      such as the extensor surfaces of the forearms, fingers, and occiput, but have
      also been reported to occur in unusual locations including the central nervous
      system, pericardium, pleura, and sclera. We present the unusual case of
      rheumatoid nodules in the small bowel mesentery masquerading as an intra
      abdominal malignancy. CASE PRESENTATION: A 65-year-old-male with a known history
      of longstanding erosive, nodular, seropositive rheumatoid arthritis was
      incidentally found to have a mesenteric mass on computed tomography (CT) exam of
      the abdomen. This mass had not been present on prior imaging studies and was
      worrisome for a malignancy. Attempts at noninvasive biopsy were nondiagnostic but
      consistent with a "spindle" cell neoplasm. Laparotomy revealed extensive
      thickening and fibrosis of the small bowel mesentery along with large, firm
      nodules throughout the mesentery. A limited bowel resection including a large,
      partially obstructing, nodule was performed. Pathology was consistent with an
      unusual presentation of rheumatoid nodules in the mesentery of the small bowel.
      CONCLUSION: Rheumatoid nodules should be considered in the differential diagnosis
      of a patient who presents with an intra-abdominal mass and a history of
      rheumatoid arthritis. Currently, no tests or imaging modality can discriminate
      with sufficient accuracy to rule out a malignancy in this difficult diagnostic
      delimma. Hopefully, this case will serve as impetus for further study and
      biomarker discovery to allow for improved diagnostic power.

PMID- 19604346
TI  - Optimally timing primaquine treatment to reduce Plasmodium falciparum
      transmission in low endemicity Thai-Myanmar border populations.
AB  - BACKGROUND: Effective malaria control has successfully reduced the malaria burden
      in many countries, but to eliminate malaria, these countries will need to further
      improve their control efforts. Here, a malaria control programme was critically
      evaluated in a very low-endemicity Thai-Myanmar border population, where early
      detection and prompt treatment have substantially reduced, though not ended,
      Plasmodium falciparum transmission, in part due to carriage of late-maturing
      gametocytes that remain post-treatment. To counter this effect, the WHO
      recommends the use of a single oral dose of primaquine along with an effective
      blood schizonticide. However, while the effectiveness of primaquine as a
      gametocidal agent is widely documented, the mismatch between primaquine's short
      half-life, the long-delay for gametocyte maturation and the proper timing of
      primaquine administration have not been studied. METHODS: Mathematical models
      were constructed to simulate 8-year surveillance data, between 1999 and 2006, of
      seven villages along the Thai-Myanmar border. A simple model was developed to
      consider primaquine pharmacokinetics and pharmacodynamics, gametocyte carriage,
      and infectivity. RESULTS: In these populations, transmission intensity is very
      low, so the P. falciparum parasite rate is strongly linked to imported malaria
      and to the fraction of cases not treated. Given a 3.6-day half-life of
      gametocyte, the estimated duration of infectiousness would be reduced by 10 days
      for every 10-fold reduction in initial gametocyte densities. Infectiousness from
      mature gametocytes would last two to four weeks and sustain some transmission,
      depending on the initial parasite densities, but the residual mature gametocytes
      could be eliminated by primaquine. Because of the short half-life of primaquine
      (approximately eight hours), it was immediately obvious that with early
      administration (within three days after an acute attack), primaquine would not be
      present when mature gametocytes emerged eight days after the appearance of
      asexual blood-stage parasites. A model of optimal timing suggests that primaquine
      follow-up approximately eight days after a clinical episode could further reduce
      the duration of infectiousness from two to four weeks down to a few days. The
      prospects of malaria elimination would be substantially improved by changing the
      timing of primaquine administration and combining this with effective detection
      and management of imported malaria cases. The value of using primaquine to reduce
      residual gametocyte densities and to reduce malaria transmission was considered
      in the context of a malaria transmission model; the added benefit of the
      primaquine follow-up treatment would be relatively large only if a high fraction
      of patients (>95%) are initially treated with schizonticidal agents. CONCLUSION:
      Mathematical models have previously identified the long duration of P. falciparum
      asexual blood-stage infections as a critical point in maintaining malaria
      transmission, but infectiousness can persist for two to four weeks because of
      residual populations of mature gametocytes. Simulations from new models suggest
      that, in areas where a large fraction of malaria cases are treated, curing the
      asexual parasitaemia in a primary infection, and curing mature gametocyte
      infections with an eight-day follow-up treatment with primaquine have
      approximately the same proportional effects on reducing the infectious period.
      Changing the timing of primaquine administration would, in all likelihood,
      interrupt transmission in this area with very good health systems and with very
      low endemicity.

PMID- 19604348
TI  - Failure of hospital employees to comply with smoke-free policy is associated with
      nicotine dependence and motives for smoking: a descriptive cross-sectional study
      at a teaching hospital in the United Kingdom.
AB  - BACKGROUND: Smoke-free policy aims to protect the health of the population by
      reducing exposure to environmental tobacco smoke (ETS), and World Health
      Organisation (WHO) guidance notes that these policies are only successful if
      there is full and proper enforcement. We aimed to investigate the problem of
      resistance to smoking restrictions and specifically compliance with smoke-free
      policy. We hypothesised that an explanation for non-compliance would lie in a
      measurable difference between the smoking behaviours of compliant and non
      compliant smokers, specifically that non-compliance would be associated with
      nicotine dependence and different reasons for smoking. METHODS: We conducted a
      questionnaire-based, descriptive, cross-sectional study of hospital employees.
      Seven hundred and four members of staff at Addenbrooke's Hospital, Cambridge, UK,
      completed the questionnaire, of whom 101 were smokers. Comparison between
      compliant and non-compliant smokers was made based on calculated scores for the
      Fagerstrom test and the Horn-Waingrow scale, and level of agreement with
      questions about attitudes. For ordinal data we used a linear-by-linear
      association test. For non-parametric independent variables we used the Mann
      Whitney test and for associations between categorical variables we used the chi
      squared test. RESULTS: The demographic composition of respondents corresponded
      with the hospital's working population in gender, age, job profile and ethnicity.
      Sixty nine smokers reported they were compliant while 32 were non-compliant.
      Linear-by-linear association analysis of the compliant and non-compliant smokers'
      answers for the Fagerstrom test suggests association between compliance and
      nicotine dependence (p = 0.049). Mann-Whitney test analysis suggests there is a
      statistically significant difference between the reasons for smoking of the two
      groups: specifically that non-compliant smokers showed habitual smoking behaviour
      (p = 0.003). Overall, compliant and non-compliant smokers did not have
      significantly different attitudes towards the policy or their own health.
      CONCLUSION: We demonstrate that those who smoke in this setting in contravention
      to a smoke-free policy do so neither for pleasure (promotion of positive affect)
      nor to avoid feeling low (reduction of negative affect); instead it is a
      resistant habit, which has little or no influence on the smoker's mood, and is
      determined in part by chemical dependence.

PMID- 19604349
TI  - Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node
      metastases in breast cancer.
AB  - BACKGROUND: There is evidence that the immune systems of patients with breast
      cancer are dysfunctional. Regulatory T cells (Tregs), and IDO, an
      immunosuppressive enzyme, are associated with more advanced disease in some
      cancers and may promote immunologic tolerance to tumors. Our aim was to assess
      whether expression of Foxp3, a marker of Tregs, and IDO were linked with nodal
      metastasis in breast cancer patients. Inhibitors of IDO are available and could
      potentially demonstrate utility in breast cancer if IDO drives progression of
      disease. METHODS: Sentinel lymph nodes (SLN) of 47 breast cancer patients with
      varying degrees of nodal disease and 10 controls were evaluated for expression of
      Foxp3 and IDO using immunohistochemistry. Positively stained cells were
      quantified and their distribution within the SLN noted. RESULTS: The proportion
      of Foxp3+ cells was higher in SLN of cancer patients than controls (19% v. 10%, p
      < 0.001). Specifically, there were more Foxp3+ cells in SLN with metastasis than
      tumor-free SLN (20% v. 14%, p = 0.02). The proportion IDO+ cell in SLN of cancer
      patients was not statistically different than controls (4.0% v. 1.6%, p = 0.08).
      In order to demonstrate the combined immunosuppressive effect of Foxp3 and IDO,
      we categorized each SLN as positive or negative for Foxp3 and IDO. The
      Foxp3+/IDO+ group almost exclusively consisted of cancer patients with node
      positive disease. CONCLUSION: In conclusion, our study shows that Foxp3+ cells
      are associated with more advanced disease in breast cancer, a finding that is
      proving to be true in many other cancers. As IDO has been found to promote
      differentiation of Tregs, IDO may become a suitable target to abrogate the
      development of T-cell tolerance and to promote an effective immune response to
      breast cancer. Our results about the combined expression of IDO and Foxp3 in
      metastastic SLN support this assumption.

PMID- 19604350
TI  - Divergence in function and expression of the NOD26-like intrinsic proteins in
      plants.
AB  - BACKGROUND: NOD26-like intrinsic proteins (NIPs) that belong to the aquaporin
      superfamily are plant-specific and exhibit a similar three-dimensional structure.
      Experimental evidences however revealed that functional divergence should have
      extensively occurred among NIP genes. It is therefore intriguing to further
      investigate the evolutionary mechanisms being responsible for the functional
      diversification of the NIP genes. To better understand this process, a
      comprehensive analysis including the phylogenetic, positive selection, functional
      divergence, and transcriptional analysis was carried out. RESULTS: The
      origination of NIPs could be dated back to the primitive land plants, and their
      diversification would be no younger than the emergence time of the moss P.
      patens. The rapid proliferation of NIPs in plants may be primarily attributed to
      the segmental chromosome duplication produced by polyploidy and tandem
      duplications. The maximum likelihood analysis revealed that NIPs should have
      experienced strong selective pressure for adaptive evolution after gene
      duplication and/or speciation, prompting the formation of distinct NIP groups.
      Functional divergence analysis at the amino acid level has provided strong
      statistical evidence for shifted evolutionary rate and/or radical change of the
      physiochemical properties of amino acids after gene duplication, and DIVERGE2 has
      identified the critical amino acid sites that are thought to be responsible for
      the divergence for further investigation. The expression of plant NIPs displays a
      distinct tissue-, cell-type-, and developmental specific pattern, and their
      responses to various stress treatments are quite different also. The differences
      in organization of cis-acting regulatory elements in the promoter regions may
      partially explain their distinction in expression. CONCLUSION: A number of
      analyses both at the DNA and amino acid sequence levels have provided strong
      evidences that plant NIPs have suffered a high divergence in function and
      expression during evolution, which is primarily attributed to the strong positive
      selection or a rapid change of evolutionary rate and/or physiochemical properties
      of some critical amino acid sites.

PMID- 19604352
TI  - Direct current induced short-term modulation of the left dorsolateral prefrontal
      cortex while learning auditory presented nouns.
AB  - BACKGROUND: Little is known about the contribution of transcranial direct current
      stimulation (tDCS) to the exploration of memory functions. The aim of the present
      study was to examine the behavioural effects of right or left-hemisphere frontal
      direct current delivery while committing to memory auditory presented nouns on
      short-term learning and subsequent long-term retrieval. METHODS: Twenty subjects,
      divided into two groups, performed an episodic verbal memory task during anodal,
      cathodal and sham current application on the right or left dorsolateral
      prefrontal cortex (DLPFC). RESULTS: Our results imply that only cathodal tDCS
      elicits behavioural effects on verbal memory performance. In particular, left
      sided application of cathodal tDCS impaired short-term verbal learning when
      compared to the baseline. We did not observe tDCS effects on long-term retrieval.
      CONCLUSION: Our results imply that the left DLPFC is a crucial area involved in
      short-term verbal learning mechanisms. However, we found further support that
      direct current delivery with an intensity of 1.5 mA to the DLPFC during short
      term learning does not disrupt longer lasting consolidation processes that are
      mainly known to be related to mesial temporal lobe areas. In the present study,
      we have shown that the tDCS technique has the potential to modulate short-term
      verbal learning mechanism.

PMID- 19604351
TI  - Promoting mental health in small-medium enterprises: an evaluation of the
      "Business in Mind" program.
AB  - BACKGROUND: Workplace mental health promotion (WMHP) aims to prevent and
      effectively manage the social and economic costs of common mental illnesses such
      as depression. The mental health of managers and employees within small-medium
      enterprises (SMEs) is a neglected sector in occupational health research and
      practice, despite the fact that this sector is the most common work setting in
      most economies. The availability and propensity of SME staff to attend face-to
      face training/therapy or workshop style interventions often seen in corporate or
      public sector work settings is a widely recognised problem. The 'Business in
      Mind' program employs a DVD mode of delivery that is convenient for SME managers,
      particularly those operating in regional and remote areas where internet delivery
      may not be optimal. The objective of the intervention program is to improve the
      mental health of SME managers, and examine whether employees of managers' whose
      mental health improves, report positive change in their psychosocial work
      environment. The mechanisms via which we aim to improve managers' mental health
      are through the development of their psychological capital (a higher order
      construct comprised of hope, self efficacy, resilience and optimism) and their
      skills and capacities for coping with work stress. METHODS/DESIGN: The
      effectiveness of two versions of the program (self administered and telephone
      facilitated) will be assessed using a randomised trial with an active control
      condition (psychoeducation only). We aim to recruit a minimum of 249 managers and
      a sample of their employees. This design allows for 83 managers per group, as
      power analyses showed that this number would allow for attrition of 20% and still
      enable detection of an effect size of 0.5. The intervention will be implemented
      over a three month period and postal surveys will assess managers and employees
      in each group at baseline, intervention completion, and at 6 month follow up. The
      intervention groups (managers only) will also be assessed at 12 and 24 month
      follow-up to examine maintenance of effects. Primary outcomes are managers'
      levels of psychological capital (hope, resilience, self-efficacy and optimism),
      coping strategies, anxiety and depression symptoms, self-reported health, job
      satisfaction and job tension. Secondary outcomes are participating managers
      subordinates' perceptions of manager support, relational justice, emotional
      climate and job tension. In order to provide an economic evaluation of the
      intervention, both employees and manager rates of absenteeism and presenteeism
      will also be assessed. DISCUSSION: The intervention being trialled is expected to
      improve both primary and secondary outcomes. If proven efficacious, the
      intervention could be disseminated to reach a much larger proportion of the
      business community.

PMID- 19604353
TI  - The Keele community knee pain forum: action research to engage with stakeholders
      about the prevention of knee pain and disability.
AB  - BACKGROUND: Involvement of users in health care research is central to UK health
      care policy, and guidelines for involvement exist. However, there are limited
      examples in rheumatology research. The aim of this study was to establish a
      community knee pain forum aimed at engaging stakeholders in design, dissemination
      and prioritisation of knee pain research. METHODS: Ten people were recruited to
      the forum representing a wide range of agencies. These included Weight Watchers,
      the leisure industry, Beth Johnson Foundation, health and social care
      professionals and the public. Three two-hour meetings over a two-year period were
      held. Experienced qualitative researchers facilitated each meeting. Written
      feedback after each meeting was elicited, and a short evaluation form was mailed
      to all members after the final meeting. RESULTS: Establishing and maintaining a
      forum of mixed members required careful preparation and ongoing support. Meetings
      had to be well-structured in order to allow for balanced participation of lay and
      professional users. Users contributed to the design of methods, provided ideas
      for dissemination and set priorities for further research. Clear documentation of
      meetings ensured that users' contributions to the research cycle were
      transparent. CONCLUSION: Our knee pain forum illustrates that community
      engagement can have a positive impact on the development, dissemination and
      implementation of health research. Engaging with non-academic partners enables
      mutual learning and this enhances the quality of NHS research.

PMID- 19604354
TI  - Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (SCC) represents one of the most
      malignant tumors. To improve the poor prognosis, it is necessary to diagnose
      esophageal SCC at early stages using new tumor markers. SEREX (serological
      identification of antigens by recombinant cDNA expression cloning) is suitable
      for large-scale screening of tumor antigens and has been applied for various
      types of human tumors. METHODS: Tumor markers of esophageal squamous cell
      carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin
      1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using
      bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in
      tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by
      transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated
      proteins in MKRN1-transfected cells were identified by immunoprecipitation with
      anti-ubiquitin antibody followed by mass spectrometry. RESULTS: MKRN1 was
      identified as a novel SEREX antigen of esophageal SCC. Although a total of 18
      (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy
      donors had a detectable level of s-MKRN1-Abs. There was no correlation between
      the presence of s-MKRN1-Abs and clinicopathological variables other than
      histological grading. Well-differentiated tumors were associated significantly
      with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were
      frequently higher in esophageal SCC tissues than in the peripheral normal
      esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA
      induced prominent morphological changes such as enlargement of the cell body and
      spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in
      MKRN1-transfected cells but not in the parental cells, which were identified as L
      FILIP (filamin A interacting protein 1). CONCLUSION: MKRN1 is a novel SEREX
      antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic
      markers of esophageal SCC with high specificity. It is plausible that MKRN1 is
      involved in carcinogenesis of the well-differentiated type of tumors possibly via
      ubiquitination of L-FILIP.

PMID- 19604355
TI  - Complement factor H binding by different Lyme disease and relapsing fever
      Borrelia in animals and human.
AB  - BACKGROUND: Borreliae employ multiple immune evasive strategies such as binding
      to complement regulatory proteins [factor H (fH) and factor H like-1 (FHL1)],
      differential regulation of surface membrane proteins, antigenic variation, and
      binding of plasminogen/plasmin and matrix metalloproteinases. As a complement
      regulatory subunit, fH serves as a cofactor for the factor I-mediated cleavage of
      C3b. fH binding by Borrelia has been correlated with pathogenesis as well as with
      host diversity. Here we show the differential binding of borrelial proteins to fH
      from human and animal sera. FINDINGS: Affinity ligand binding experiments, 2-D
      electrophoresis, and protein identification and peptide de novo sequencing based
      on mass spectrometry, revealed novel fH putative binding proteins of Lyme- and
      relapsing fever Borrelia. An OspA serotype-associated differential human and
      animal fH binding by B. garinii was also observed, which could be related with
      the ability of some strains from serotypes 4 and 7 to invade non-nervous system
      tissues. Also, the variable affinity of binding proteins expressed by different
      Borrelia to animal fH correlated with their host selectivity. CONCLUSION: The
      novel animal and human putative fH binding proteins (FHBPs) in this study
      underscore the importance of evasion of complement in the pathogenesis of
      Borrelia infections.

PMID- 19604356
TI  - The change and effect of endothelial progenitor cells in pig with multiple organ
      dysfunction syndromes.
AB  - INTRODUCTION: The dysfunction and decrease of endothelial progenitor cells (EPCs)
      may play a very important role in the initiation of organ dysfunction caused by
      trauma or severe sepsis. We aim to measure the number and function of EPCs in the
      progression of multiple organ dysfunction syndromes (MODS) caused by severe
      sepsis, which may help to understand the pathogenesis of MODS by the changing of
      EPCs. METHODS: A total of 40 pigs were randomly divided into two groups, which
      were subjected to hemorrhagic shock, resuscitation and endotoxemia (experimental
      group, n = 20) or acted as a control (control group, n = 20). The number and
      function of EPCs including adhesive, migratory and angiogenesis capacities were
      analyzed at different times in both groups. RESULTS: All the animals in the
      experimental group developed MODS (100%) and 17 of 20 animals (85%) died due to
      MODS; the incidence of MODS and death of the animals in the control group were 0%
      (P < 0.01). The number, migratory and adhesive capacities of EPCs decreased
      sharply in the animals of the experimental group corresponding to the increasing
      severities of MODS, but the angiogenesis function increased gradually until
      death. The decrease in function of EPCs preceded the decrease in number of EPCs.
      The decrease in number and function of EPCs occurred prior to the occurrence of
      MODS. CONCLUSIONS: For the first time, it was observed that the number and
      function of EPCs decreased sharply in the progression of MODS and that it was
      prior to the occurrence of MODS. The decrease in number and function of EPCs may
      be one of the main pathogenic factors of MODS.

PMID- 19604357
TI  - Predictors of major infections in systemic lupus erythematosus.
AB  - INTRODUCTION: Infections commonly complicate the course of systemic lupus
      erythematosus (SLE). Our aim is to investigate the clinical predictors of major
      infections in patients with SLE. METHODS: A nested case-control study design was
      used within the prospective Lupus-Cruces cohort. The endpoints of the study were
      major infections. Cases were defined as patients with a major infection. Two
      controls (SLE patients without major infections), matched for time of follow-up
      until the event and age at diagnosis, were selected for each case. Univariate
      analysis and logistic regression models were used for the analysis of data.
      RESULTS: Two hundred and forty-nine patients (83 cases, 166 controls) were
      selected. Eighty-three episodes of major infections were analyzed; E. coli, S.
      aureus, M. tuberculosis and S. pneumoniae being the most frequent isolates.
      Univariate analysis identified several variables related with infection: lung and
      renal involvement, at or previous to the study point; leukopenia at the study
      point; antiphospholipid antibody-positivity and treatment with prednisone within
      3 months previous to the study point, and the dose of prednisone received.
      Treatment with antimalarials, on the other hand, showed a strong inverse
      association with major infections. Logistic regression models identified
      treatment with antimalarials (odds ratio (OR) = 0.06, 95% confidence interval
      (CI) = 0.02 to 0.18), prednisone dose (OR = 1.12, 95% CI = 1.04 to 1.19) and lung
      involvement (OR = 4.41, 95% CI = 1.06 to 18.36) as significant and independent
      predictors of major infections. No significant interactions among these three
      variables were found. Further adjustment for potential confounders related with
      antimalarial treatment did not change the results. CONCLUSIONS: The risk of major
      infections in patients with SLE is mostly influenced by treatment. Prednisone
      treatment, even at moderate doses, increases the risk, whilst antimalarials have
      a protective effect.

PMID- 19604358
TI  - Anti-fibrinolytic agents in post partum haemorrhage: a systematic review.
AB  - BACKGROUND: Post partum haemorrhage is a leading cause of maternal death
      worldwide. It also contributes to maternal morbidity as women may require a
      hysterectomy to control bleeding, or may require a blood transfusion, which can
      transmit viral infections. Anti-fibrinolytic agents have been proposed as a
      treatment for post partum haemorrhage. We conducted a systematic review to assess
      the effectiveness and safety of anti-fibrinolytic agents in post partum bleeding.
      METHODS: All randomised controlled trials of anti-fibrinolytic agents given for
      bleeding during the postpartum period were included in this review. We searched
      Medline, PubMed, EMBASE, Cochrane Central Register of Controlled trials, Web of
      Science, metaRegister of controlled trials, LILACS, Reproductive Health Library,
      African healthline, POPLINE, MedCarib, CINAHL, Clinicaltrials.gov and the
      reference lists of eligible trials. Two authors extracted data. Methodological
      quality was assessed by evaluating allocation concealment. The primary outcome
      was maternal mortality. Secondary outcomes were blood loss, blood transfusion,
      hysterectomy, mean haemoglobin concentration, thrombo-embolic events and other
      adverse effects. RESULTS: We identified three randomised controlled trials
      involving 461 participants. The trials compared tranexamic acid with no treatment
      and reported blood loss after delivery. In all three trials, allocation
      concealment was either inadequate or unclear. The administration of tranexamic
      acid was associated with a reduction in blood loss of 92 millilitres (95%CI 76 to
      109). The most frequently reported adverse effect of tranexamic acid was nausea,
      although the increase was easily compatible with the play of chance (RR 4.63,
      95%CI 0.23 to 95.14). CONCLUSION: Tranexamic acid may reduce blood loss in post
      partum haemorrhage. However, the quality of the currently available evidence is
      poor. Adequately powered, high quality randomised controlled trials are needed.

PMID- 19604360
TI  - Interactome and Gene Ontology provide congruent yet subtly different views of a
      eukaryotic cell.
AB  - BACKGROUND: The characterization of the global functional structure of a cell is
      a major goal in bioinformatics and systems biology. Gene Ontology (GO) and the
      protein-protein interaction network offer alternative views of that structure.
      RESULTS: This study presents a comparison of the global structures of the Gene
      Ontology and the interactome of Saccharomyces cerevisiae. Sensitive, unsupervised
      methods of clustering applied to a large fraction of the proteome led to
      establish a GO-interactome correlation value of +0.47 for a general dataset that
      contains both high and low-confidence interactions and +0.58 for a smaller, high
      confidence dataset. CONCLUSION: The structures of the yeast cell deduced from GO
      and interactome are substantially congruent. However, some significant
      differences were also detected, which may contribute to a better understanding of
      cell function and also to a refinement of the current ontologies.

PMID- 19604359
TI  - The Karachi intracranial stenosis study (KISS) Protocol: an urban multicenter
      case-control investigation reporting the clinical, radiologic and biochemical
      associations of intracranial stenosis in Pakistan.
AB  - BACKGROUND: Intracranial stenosis is the most common cause of stroke among
      Asians. It has a poor prognosis with a high rate of recurrence. No effective
      medical or surgical treatment modality has been developed for the treatment of
      stroke due to intracranial stenosis. We aim to identify risk factors and
      biomarkers for intracranial stenosis and to develop techniques such as use of
      transcranial doppler to help diagnose intracranial stenosis in a cost-effective
      manner. METHODS/DESIGN: The Karachi Intracranial Stenosis Study (KISS) is a
      prospective, observational, case-control study to describe the clinical features
      and determine the risk factors of patients with stroke due to intracranial
      stenosis and compare them to those with stroke due to other etiologies as well as
      to unaffected individuals. We plan to recruit 200 patients with stroke due to
      intracranial stenosis and two control groups each of 150 matched individuals. The
      first set of controls will include patients with ischemic stroke that is due to
      other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes.
      The second group will consist of stroke free individuals. Standardized interviews
      will be conducted to determine demographic, medical, social, and behavioral
      variables along with baseline medications. Mandatory procedures for inclusion in
      the study are clinical confirmation of stroke by a healthcare professional within
      72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition,
      lipid profile, serum glucose, creatinine and HbA1C will be measured in all
      participants. Ancillary tests will include carotid ultrasound, transcranial
      doppler and magnetic resonance or computed tomography angiogram to rule out
      concurrent carotid disease. Echocardiogram and other additional investigations
      will be performed at these centers at the discretion of the regional physicians.
      DISCUSSION: The results of this study will help inform locally relevant clinical
      guidelines and effective public health and individual interventions.

PMID- 19604361
TI  - The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for
      thymocyte development.
AB  - BACKGROUND: SH3 containing Lymphocyte Protein (SLY1) is a putative adapter
      protein exclusively expressed in lymphocytes which is involved in antigen
      receptor induced activation. We previously have generated SLY1Delta/Delta mice
      harbouring a partial deletion in the N-terminal region of SLY1 which revealed
      profound immunological defects in T and B cell functions. RESULTS: In this study,
      T cell development in SLY1-/- and SLY1Delta/Delta mice was analysed ex vivo and
      upon cultivation with the bone marrow stromal cell line OP9. SLY1-deficient
      thymocytes were compromised in inducing nutrient receptor expression and
      ribosomal protein S6 phosphorylation, indicating a defect in mTOR complex
      activation. Furthermore, SLY1 was identified as a novel anti-apoptotic protein
      required for developmental progression of T cell precursors to the CD4+CD8+
      double-positive stage by protecting from premature programmed cell death
      initiation in developing CD4-CD8- double-negative thymocytes. In addition, SLY1
      phosphorylation was differentially regulated upon Notch ligand-mediated
      stimulation and expression of the preTCR. CONCLUSION: Thus, our results suggest a
      non-redundant role for SLY1 in integrating signals from both receptors in early T
      cell progenitors in the thymus.

PMID- 19604362
TI  - Disassembled DJ-1 high molecular weight complex in cortex mitochondria from
      Parkinson's disease patients.
AB  - Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1
      high molecular weight complex in cortex mitochondria from Parkinson's disease
      patients Molecular Neurodegeneration 2009, 4:23.

PMID- 19604363
TI  - A set of EST-SNPs for map saturation and cultivar identification in melon.
AB  - BACKGROUND: There are few genomic tools available in melon (Cucumis melo L.), a
      member of the Cucurbitaceae, despite its importance as a crop. Among these tools,
      genetic maps have been constructed mainly using marker types such as simple
      sequence repeats (SSR), restriction fragment length polymorphisms (RFLP) and
      amplified fragment length polymorphisms (AFLP) in different mapping populations.
      There is a growing need for saturating the genetic map with single nucleotide
      polymorphisms (SNP), more amenable for high throughput analysis, especially if
      these markers are located in gene coding regions, to provide functional markers.
      Expressed sequence tags (ESTs) from melon are available in public databases, and
      resequencing ESTs or validating SNPs detected in silico are excellent ways to
      discover SNPs. RESULTS: EST-based SNPs were discovered after resequencing ESTs
      between the parental lines of the PI 161375 (SC) x 'Piel de sapo' (PS) genetic
      map or using in silico SNP information from EST databases. In total 200 EST-based
      SNPs were mapped in the melon genetic map using a bin-mapping strategy,
      increasing the map density to 2.35 cM/marker. A subset of 45 SNPs was used to
      study variation in a panel of 48 melon accessions covering a wide range of the
      genetic diversity of the species. SNP analysis correctly reflected the genetic
      relationships compared with other marker systems, being able to distinguish all
      the accessions and cultivars. CONCLUSION: This is the first example of a genetic
      map in a cucurbit species that includes a major set of SNP markers discovered
      using ESTs. The PI 161375 x 'Piel de sapo' melon genetic map has around 700
      markers, of which more than 500 are gene-based markers (SNP, RFLP and SSR). This
      genetic map will be a central tool for the construction of the melon physical
      map, the step prior to sequencing the complete genome. Using the set of SNP
      markers, it was possible to define the genetic relationships within a collection
      of forty-eight melon accessions as efficiently as with SSR markers, and these
      markers may also be useful for cultivar identification in Occidental melon
      varieties.

PMID- 19604364
TI  - In silico identification of a core regulatory network of OCT4 in human embryonic
      stem cells using an integrated approach.
AB  - BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent
      embryonic stem cells which are derived from the inner cell mass of mammalian
      blastocysts. Pluripotency and self renewal are controlled by a transcription
      regulatory network governed by the transcription factors OCT4, SOX2 and NANOG.
      Recent studies on reprogramming somatic cells to induced pluripotent stem cells
      highlight OCT4 as a key regulator of pluripotency. RESULTS: We have carried out
      an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments
      along with promoter sequence analysis of putative target genes) and identified a
      core OCT4 regulatory network in human embryonic stem cells consisting of 33
      target genes. Enrichment analysis with these target genes revealed that this
      integrative analysis increases the functional information content by factors of
      1.3 - 4.7 compared to the individual studies. In order to identify potential
      regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition
      to known validated OCT4 motifs we obtained binding sites similar to motifs
      recognized by further regulators of pluripotency and development; e.g. the
      heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC
      transcriptional activity that leads to cell growth and proliferation. CONCLUSION:
      Our analysis shows how heterogeneous functional information can be integrated in
      order to reconstruct gene regulatory networks. As a test case we identified a
      core OCT4-regulated network that is important for the analysis of stem cell
      characteristics and cellular differentiation. Functional information is largely
      enriched using different experimental results. The de novo motif discovery
      identified well-known regulators closely connected to the OCT4 network as well as
      potential new regulators of pluripotency and differentiation. These results
      provide the basis for further targeted functional studies.

PMID- 19604365
TI  - P2CS: a two-component system resource for prokaryotic signal transduction
      research.
AB  - BACKGROUND: With the escalation of high throughput prokaryotic genome sequencing,
      there is an ever-increasing need for databases that characterise, catalogue and
      present data relating to particular gene sets and genomes/metagenomes. Two
      component system (TCS) signal transduction pathways are the dominant mechanisms
      by which micro-organisms sense and respond to external as well as internal
      environmental changes. These systems respond to a wide range of stimuli by
      triggering diverse physiological adjustments, including alterations in gene
      expression, enzymatic reactions, or protein-protein interactions. DESCRIPTION: We
      present P2CS (Prokaryotic 2-Component Systems), an integrated and comprehensive
      database of TCS signal transduction proteins, which contains a compilation of the
      TCS genes within 755 completely sequenced prokaryotic genomes and 39 metagenomes.
      P2CS provides detailed annotation of each TCS gene including family
      classification, sequence features, functional domains, as well as genomic context
      visualization. To bypass the generic problem of gene underestimation during
      genome annotation, we also constituted and searched an ORFeome, which improves
      the recovery of TCS proteins compared to searches on the equivalent proteomes.
      CONCLUSION: P2CS has been developed for computational analysis of the modular
      TCSs of prokaryotic genomes and metagenomes. It provides a complete overview of
      information on TCSs, including predicted candidate proteins and probable
      proteins, which need further curation/validation. The database can be browsed and
      queried with a user-friendly web interface at http://www.p2cs.org/.

PMID- 19604366
TI  - Estrous cycle influences the expression of neuronal nitric oxide synthase in the
      hypothalamus and limbic system of female mice.
AB  - BACKGROUND: Nitric oxide plays an important role in the regulation of male and
      female sexual behavior in rodents, and the expression of the nitric oxide
      synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in
      the female. We have here quantitatively investigated the distribution of nNOS
      immunoreactive (ir) neurons in the limbic hypothalamic region of intact female
      mice sacrificed during different phases of estrous cycle. RESULTS: Changes were
      observed in the medial preoptic area (MPA) (significantly higher number in
      estrus) and in the arcuate nucleus (Arc) (significantly higher number in
      proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in
      the bed nucleus of the stria terminalis (BST) no significant changes have been
      observed. In addition, by comparing males and females, we observed a stable sex
      dimorphism (males have a higher number of nNOS-ir cells in comparison to almost
      all the different phases of the estrous cycle) in the VMHvl and in the BST (when
      considering only the less intensely stained elements). In the MPA and in the Arc
      sex differences were detected only comparing some phases of the cycle.
      CONCLUSION: These data demonstrate that, in mice, the expression of nNOS in some
      hypothalamic regions involved in the control of reproduction and characterized by
      a large number of estrogen receptors is under the control of gonadal hormones and
      may vary according to the rapid variations of hormonal levels that take place
      during the estrous cycle.

PMID- 19604367
TI  - Genomic resources of Magnaporthe oryzae (GROMO): a comprehensive and integrated
      database on rice blast fungus.
AB  - BACKGROUND: Magnaporthe oryzae, rice blast fungus, is the most devastating
      pathogen of rice. It has emerged as a model phytopathogen for the study of host
      pathogen interactions. A large body of data has been generated on different
      aspects of biology of this fungus and on host-pathogen interactions. However,
      most of the data is scattered and is not available as a single resource for
      researchers in this field. DESCRIPTION: Genomic Resources of Magnaporthe oyzae
      (GROMO), is a specialized, and comprehensive database for rice blast fungus,
      integrating information from several resources. GROMO contains information on
      genomic sequence, mutants available, gene expression, localization of proteins
      obtained from a variety of repositories, as primary data. In addition, prediction
      of domains, pathways, protein-protein interactions, sumolyation sites and
      biochemical properties that were obtained after computational analysis of protein
      sequences have also been included as derived data. This database has an intuitive
      user interface that shall prompt the user to explore various possible information
      resources available on a given gene or a protein, from a single source.
      CONCLUSION: Currently, information on M. oryzae is available from different
      resources like BROAD MIT Magnaporthe database, Agrobacterium tumefaciens-mediated
      transformation (ATMT) M. oryzae database, Magnaporthe grisea--Oryza sativa (MGOS)
      and Massive Parallel Signature Sequencing (MPSS) databases. In the GROMO project,
      an effort has been made to integrate information from all these databases, derive
      some new data based on the available information analyzed by relevant programs
      and make more insightful predictions to better understand the biology of M.
      oryzae. The database is currently available at: http://gromo.msubiotech.ac.in/

PMID- 19604368
TI  - Rooting human parechovirus evolution in time.
AB  - BACKGROUND: The Picornaviridae family contains a number of important pathogenic
      viruses, among which the recently reclassified human parechoviruses (HPeVs).
      These viruses are widespread and can be grouped in several types. Understanding
      the evolutionary history of HPeV could answer questions such as how long the
      circulating lineages last shared a common ancestor and how the evolution of this
      viral species is shaped by its population dynamics. Using both strict and relaxed
      clock Bayesian phylogenetics we investigated 1) the substitutions rates of the
      structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently
      circulating HPeV lineages. RESULTS: Our estimates reveal that human
      parechoviruses exhibit high substitution rates for both structural P1 and capsid
      VP1 regions, respectively 2.21 x 10(-3) (0.48 - 4.21 x 10(-3)) and 2.79 x 10(-3)
      (2.05 - 3.66 x 10(-3)) substitutions per site per year. These are within the
      range estimated for other picornaviruses. By employing a constant population size
      coalescent prior, the date of the most recent common ancestor was estimated to be
      at around 1600 (1427-1733). In addition, by looking at the frequency of
      synonymous and non-synonymous substitutions within the VP1 gene we show that
      purifying selection constitutes the dominating evolutionary force leading to
      strong amino acid conservation. CONCLUSION: In conclusion, our estimates provide
      a timescale for the evolution of HPeVs and suggest that genetic diversity of
      current circulating HPeV types has arisen about 400 years ago.

PMID- 19604369
TI  - Fever treatment in the absence of malaria transmission in an urban informal
      settlement in Nairobi, Kenya.
AB  - BACKGROUND: In sub-Saharan Africa, knowledge of malaria transmission across
      rapidly proliferating urban centres and recommendations for its prevention or
      management remain poorly defined. This paper presents the results of an
      investigation into infection prevalence and treatment of recent febrile events
      among a slum population in Nairobi, Kenya. METHODS: In July 2008, a community
      based malaria parasite prevalence survey was conducted in Korogocho slum, which
      forms part of the Nairobi Urban Health and Demographic Surveillance system.
      Interviewers visited 1,069 participants at home and collected data on reported
      fevers experienced over the preceding 14 days and details on the treatment of
      these episodes. Each participant was tested for malaria parasite presence with
      Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed
      to assess the period prevalence of reported fever episodes and treatment
      behaviour. RESULTS: Of the 1,069 participants visited, 983 (92%) consented to be
      tested. Three were positive for Plasmodium falciparum using RDT; however, all
      were confirmed negative on microscopy. Microscopic examination of all 953
      readable slides showed zero prevalence. Overall, from the 1,004 participants who
      have data on fever, 170 fever episodes were reported giving a relatively high
      period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below
      five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment
      information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly
      sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal
      health facility. Only four episodes were managed using the nationally recommended
      first-line treatment, artemether-lumefantrine. CONCLUSION: The study could not
      demonstrate any evidence of malaria in Korogocho, a slum in the centre of
      Nairobi. Fever was a common complaint and often treated as malaria with anti
      malarial drugs. Strategies, including testing for malaria parasites to reduce the
      inappropriate exposure of poor communities to expensive anti-malarial drugs
      provided by clinical services and drug vendors, should be a priority for district
      planners.

PMID- 19604371
TI  - Interactive visualization of clusters in microarray data: an efficient tool for
      improved metabolic analysis of E. coli.
AB  - BACKGROUND: Interpretation of comprehensive DNA microarray data sets is a
      challenging task for biologists and process engineers where scientific assistance
      of statistics and bioinformatics is essential. Interdisciplinary cooperation and
      concerted development of software-tools for simplified and accelerated data
      analysis and interpretation is the key to overcome the bottleneck in data
      analysis workflows. This approach is exemplified by gcExplorer an interactive
      visualization toolbox based on cluster analysis. Clustering is an important tool
      in gene expression data analysis to find groups of co-expressed genes which can
      finally suggest functional pathways and interactions between genes. The
      visualization of gene clusters gives practitioners an understanding of the
      cluster structure of their data and makes it easier to interpret the cluster
      results. RESULTS: In this study the interactive visualization toolbox gcExplorer
      is applied to the interpretation of E. coli microarray data. The data sets derive
      from two fedbatch experiments conducted in order to investigate the impact of
      different induction strategies on the host metabolism and product yield. The
      software enables direct graphical comparison of these two experiments. The
      identification of potentially interesting gene candidates or functional groups is
      substantially accelerated and eased. CONCLUSION: It was shown that gcExplorer is
      a very helpful tool to gain a general overview of microarray experiments.
      Interesting gene expression patterns can easily be found, compared among
      different experiments and combined with information about gene function from
      publicly available databases.

PMID- 19604370
TI  - Data enhancement for co-morbidity measurement among patients referred for sleep
      diagnostic testing: an observational study.
AB  - BACKGROUND: Observational outcome studies of patients with obstructive sleep
      apnea (OSA) require adjustment for co-morbidity to produce valid results. The aim
      of this study was to evaluate whether the combination of administrative data and
      self-reported data provided a more complete estimate of co-morbidity among
      patients referred for sleep diagnostic testing. METHODS: A retrospective
      observational study of 2149 patients referred for sleep diagnostic testing in
      Calgary, Canada. Self-reported co-morbidity was obtained with a questionnaire;
      administrative data and validated algorithms (when available) were also used to
      define the presence of these co-morbid conditions within a two-year period prior
      to sleep testing. RESULTS: Patient self-report of co-morbid conditions had
      varying levels of agreement with those derived from administrative data, ranging
      from substantial agreement for diabetes (kappa = 0.79) to poor agreement for
      cardiac arrhythmia (kappa = 0.14). The enhanced measure of co-morbidity using
      either self-report or administrative data had face validity, and provided
      clinically meaningful trends in the prevalence of co-morbidity among this
      population. CONCLUSION: An enhanced measure of co-morbidity using self-report and
      administrative data can provide a more complete measure of the co-morbidity among
      patients with OSA when agreement between the two sources is poor. This
      methodology will aid in the adjustment of these coexisting conditions in
      observational studies in this area.

PMID- 19604372
TI  - Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat
      diet induced atherosclerosis.
AB  - Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth
      muscle cell proliferation, a key mediator of atherosclerosis. This study tests if
      p2l deficiency will result in severe atherosclerosis in a mouse model. p21-/- and
      strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis
      for biochemical parameters (cholesterol, triglycerides) in serum and mRNA
      expression of CD36, HO-1, TGF-beta, IFN-gamma, TNF-alpha, PPAR-gamma and NADPH
      oxidase components (p22phox, NOX-1 and Rac-1) was performed in aortic tissues by
      Real Time PCR. p21-/- mice gained significantly (p < 0.01) more weight than wild
      type mice, triglycerides (p < 0.05) and cholesterol levels (p < 0.01) were more
      pronounced in the sera of p21-/- compared to wild type mice fed with high fat
      diet. High fat diet resulted in significantly decreased TGF-beta (p < 0.02), HO-l
      (p < 0.02) and increased CD36 (p < 0.03) mRNA expression in aortic tissues of p21
      /- mice compared to animal fed with regular diet. IFN-gamma mRNA expression (235
      +/- 11 folds) increased significantly in high fat diet fed p21-/- mice and a
      multifold modulation of PPAR-gamma(136 +/- 7), p22phox, NOX-1 and Rac-1 (15-35
      folds) mRNA in aortic tissues from p21-/- mice compared to the wild type mice.
      Severity of atherosclerotic lesions was significantly higher in p21-/- compared
      to wild type mice. The results demonstrate that the deficiency of p21 leads to
      altered expression of pro-atherogenic genes, and severe atherosclerosis in mice
      fed with high fat diet. This opens the possibility of p21 protein as a
      therapeutic tool to control progression of atherosclerosis.

PMID- 19604373
TI  - Biomechanical testing of a polymer-based biomaterial for the restoration of
      spinal stability after nucleotomy.
AB  - BACKGROUND: Surgery for disc herniations can be complicated by two major
      problems: painful degeneration of the spinal segment and re-herniation.
      Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which
      was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish
      spinal stability and to (b) seal annulus fibrosus defects. The biomechanical
      properties range of motion (ROM), neutral zone (NZ) and a potential annulus
      sealing capacity were investigated. METHODS: Seven bovine, lumbar spinal units
      were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b)
      following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For
      biomechanical testing, spinal units were mounted on a loading-simulator for
      spines. In three cycles, axial loading was applied in an excentric mode with 0.5
      Nm steps until an applied moment of +/- 7.5 Nm was achieved in flexion/extension.
      ROM and NZ were assessed. These tests were performed without and with annulus
      sealing by sewing a PGA/HA annulus-implant into the annulus defect. RESULTS:
      Spinal stability was significantly impaired after nucleotomy (p < 0.001).
      Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal
      stability (p < 0.003). There was no statistical difference between the stability
      provided by the nucleus-implant and the intact stage regarding flexion/extension
      movements (p = 0.209). During the testing sequences, herniation of biomaterial
      through the annulus defect into the spinal canal regularly occurred, resulting in
      compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus
      defect, however, effectively prevented herniation. CONCLUSION: PGA/HA biomaterial
      seems to be well suited for cell-free and cell-based regenerative treatment
      strategies in spinal surgery. Its abilities to restore spinal stability and
      potentially close annulus defects open up new vistas for regenerative approaches
      to treat intervertebral disc degeneration and for preventing implant herniation.

PMID- 19604374
TI  - Correction: Phylogenetic placement of the enigmatic parasite, Polypodium
      hydriforme, within the Phylum Cnidaria.
AB  - Correction to Evans, N.M., Lindner, A., Raikova, E.V., Collins, A.G. and
      Cartwright, P. Phylogenetic placement of the enigmatic parasite, Polypodium
      hydriforme, within the phylum Cnidaria. BMC Evol Biol, 2008, 8:139.

PMID- 19604375
TI  - Expression of ezrin is associated with invasion and dedifferentiation of
      hepatitis B related hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in
      the world and constitutes the leading cause of cancer-related death among men,
      and second among women in Taiwan. Liver cirrhosis and HCC are relatively
      prevalent, and 80% to 85% of the patients with these conditions have positive
      results for hepatitis B surface antigen in Taiwan. Only 5% of the general
      population is seronegative for all hepatititis B virus (HBV) markers. This is the
      first study to determine the role of ezrin upon HBV HCC cell and patients with
      HBV HCC undergoing hepatectomy METHODS: Immunohistochemical study with ezrin in
      104 human HBV-HCC cases were carried out to investigate its association with the
      clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing
      hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin)
      and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role
      in tumor invasion and differentiation. RESULTS: HBV HCC patients with ezrin over
      expression independently have smaller tumor size, cirrhotic liver background,
      poor tumor differentiation, and more vascular invasion. Ezrin expression status
      has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in
      vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of
      AFP secretion and higher invasion ability as compared with the control and Y353-
      ezrin Hep3B cells. CONCLUSION: Ezrin over-expression contributed to de
      differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over
      expression were independently associated with tumor with smaller size, cirrhotic
      liver background, poor differentiation, and vascular invasion.

PMID- 19604376
TI  - Three-dimensional Huh7 cell culture system for the study of Hepatitis C virus
      infection.
AB  - BACKGROUND: In order to elucidate how Hepatitis C Virus (HCV) interacts with
      polarized hepatocytes in vivo and how HCV-induced alterations in cellular
      function contribute to HCV-associated liver disease, a more physiologically
      relevant hepatocyte culture model is needed. As such, NASA-engineered three
      dimensional (3-D) rotating wall vessel (RWV) bioreactors were used in effort to
      promote differentiation of HCV-permissive Huh7 hepatoma cells. RESULTS: When
      cultured in the RWV, Huh7 cells became morphologically and transcriptionally
      distinct from more standard Huh7 two-dimensional (2-D) monolayers. Specifically,
      RWV-cultured Huh7 cells formed complex, multilayered 3-D aggregates in which
      Phase I and Phase II xenobiotic drug metabolism genes, as well as hepatocyte
      specific transcripts (HNF4alpha, Albumin, TTR and alpha1AT), were upregulated
      compared to 2-D cultured Huh7 cells. Immunofluorescence analysis revealed that
      these HCV-permissive 3-D cultured Huh7 cells were more polarized than their 2D
      counterparts with the expression of HCV receptors, cell adhesion and tight
      junction markers (CD81, scavenger receptor class B member 1, claudin-1, occludin,
      ZO-1, beta-Catenin and E-Cadherin) significantly increased and exhibiting apical,
      lateral and/or basolateral localization. CONCLUSION: These findings show that
      when cultured in 3-D, Huh7 cells acquire a more differentiated hepatocyte-like
      phenotype. Importantly, we show that these 3D cultures are highly permissive for
      HCV infection, thus providing an opportunity to study HCV entry and the effects
      of HCV infection on host cell function in a more physiologically relevant cell
      culture system.

PMID- 19604377
TI  - Treatment with intravenous pamidronate is a good alternative in case of
      gastrointestinal side effects or contraindications for oral bisphosphonates.
AB  - BACKGROUND: In case of contraindications or intolerance during treatment with
      oral bisphosphonates (OB), administration of pamidronate intravenously is a
      widely used alternative. In this study we compared the effect on change in bone
      mineral density (BMD) of the spine and hip during long term treatment with
      pamidronate iv in comparison to OB. METHODS: We studied 61 patients receiving
      treatment for at least two years. In case of contraindications or intolerance
      (within 3 months) of an OB, pamidronate iv was started. BMD was measured on a
      Hologic 4500 and a Lunar DPX-IQ at the spine (L1-L4) and total hip. RESULTS:
      Thirty-one patients were enrolled in the OB group and 30 in the intravenous
      pamidronate group. Mean follow-up duration (SD) was 4.3 (1.3) years. We observed
      a significant increase (p < 0.001) in spinal BMD, both in the OB group (8.3%) as
      well as in the pamidronate iv group (6.1%), but no significant difference in BMD
      change between the OB and pamidronate iv groups. At the hips, we observed a
      tendency to increased BMD in both groups, 1.1% in the OB and 1.4% in the
      pamidronate iv group. CONCLUSION: We conclude that intravenous pamidronate is a
      good alternative for oral bisphosphonates in the treatment of osteoporosis in
      patients with contraindications or intolerance during treatment with oral
      bisphosphonates.

PMID- 19604378
TI  - Exploring reflective 'critical incident' documentation of professionalism lapses
      in a medical undergraduate setting.
AB  - BACKGROUND: Measuring professionalism in undergraduate medical students is a
      difficult process, and no one method has currently emerged as the definitive
      means of assessment in this field. Student skills in reflection have been shown
      to be highly important in the development of professional behaviours. By studying
      student reflections on lapses in professional judgement, recorded as 'critical
      incidents', it is possible to explore themes which are significant for the
      development of professional behaviour in an undergraduate setting. METHODS: We
      examined critical incident reporting combined with optional written student
      reflection as a method for exploring professionalism in undergraduate medical
      students. 228 students split between Year 1 and 2 of one academic year of
      undergraduate medicine were studied retrospectively and a grounded theory
      approach to analysis was employed. RESULTS: This year generated 16 critical
      incident reports and corresponding student reflections, all of which were
      considered. In addition to identifying the nature of the critical incidents, 3
      principal themes emerged. These were the impact and consequences of the report
      having been made, student reactions to the events (both positive and negative),
      and student responses regarding future actions. CONCLUSION: This study indicates
      that unprofessional behaviour can be identified and challenged by both the
      faculty and the students involved, and suggests that positive behavioural changes
      might be made with the aim of preventing future occurrences. We provide a low
      cost approach of measuring and recording professional behaviour.

PMID- 19604379
TI  - Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell
      death in vitro.
AB  - BACKGROUND: A wide range of unicellular eukaryotes have now been shown to undergo
      a form of programmed cell death (PCD) that resembles apoptosis; exhibiting
      morphological and, in some cases, biochemical markers typical of metazoans.
      However, reports that sexual and asexual stages of malaria parasites exhibit
      these markers have been challenged. Here we use a rodent malaria model,
      Plasmodium berghei, to determine whether, and what proportion of cultured
      ookinetes show signs of apoptosis-like death and extend the study to examine
      ookinetes of Plasmodium falciparum in vivo. RESULTS: Ookinetes displayed the
      following markers of PCD: loss of mitochondrial membrane potential, nuclear
      chromatin condensation, DNA fragmentation, translocation of phosphatidylserine to
      the outer surface of the cell membrane and caspase-like activity. The proportion
      of parasites expressing apoptosis markers rose with time, particularly when
      cultured in phosphate buffered saline. Some ookinetes positive for apoptosis
      markers also had compromised membranes, which could represent a late stage in the
      process. When these are included a similar proportion of ookinetes display each
      marker. Over 50% of P. falciparum ookinetes, removed from the mosquito midgut
      lumen 24 h post-infection, had nuclei containing fragmented DNA. CONCLUSION: We
      have confirmed previous reports that Plasmodium ookinetes display multiple signs
      that suggest they die by a mechanism resembling apoptosis. This occurs in vivo
      and in vitro without experimental application of triggers. Our findings support
      the hypothesis that non-necrotic mechanisms of cell death evolved before the
      advent of multicellular organisms.

PMID- 19604380
TI  - Phenotype changes and impaired function of dendritic cell subsets in patients
      with sepsis: a prospective observational analysis.
AB  - INTRODUCTION: Patients with sepsis often demonstrate severely impaired immune
      responses. The hallmark of this state of immunoparalysis is monocytic
      deactivation characterized by decreased human leukocyte antigen (HLA)-DR
      expression and reduced production of proinflammatory cytokines. Recently,
      diminished numbers of dendritic cells (DCs) were reported in patients with
      sepsis. However, little is known about DC phenotype and function in human sepsis.
      We therefore compared phenotypic and functional changes in monocyte and DC
      subsets in patients with sepsis and immunoparalysis. METHODS: In a prospective
      observational analysis, 16 consecutive patients with severe sepsis and septic
      shock (age 59.2 +/- 9.7 years, 13 male, Sequential Organ Failure Assessment score
      6.1 +/- 2.7) and immunoparalysis (monocytic HLA-DR expression < 5,000
      antibodies/cell) and 16 healthy volunteers were included. Peripheral blood DC
      counts, HLA-DR expression and ex vivo cytokine production were evaluated in
      comparison with monocyte subsets over time. RESULTS: At baseline, a profound
      reduction in the numbers of myeloid DCs (MDCs), plasmacytoid DCs (PDCs), and
      CD14dimCD16positive monocytes was observed in sepsis whereas
      CD14brightCD16negative and CD14brightCD16positive monocyte numbers were
      increased. HLA-DR expression was reduced on all monocyte and DC subsets.
      Production of proinflammatory cytokines and intracellular cytokine staining in
      response to lipopolysaccharide and lipoteichoic acid was impaired in monocyte
      subsets and MDCs, whereas IL-10 secretion was increased. IFNalpha response by
      stimulated PDCs was significantly decreased compared with controls. At day 28,
      HLA-DR expression and cytokine production of DC and monocyte subsets remained
      lower in septic patients compared with controls. CONCLUSIONS: In sepsis, long
      lasting functional deactivation is common to all circulating monocyte and DC
      subsets. In addition to decreased peripheral blood DC counts, functional
      impairment of antigen-presenting cells may contribute to an impaired
      antimicrobial defense in sepsis.

PMID- 19604381
TI  - Do the socioeconomic impacts of antiretroviral therapy vary by gender? A
      longitudinal study of Kenyan agricultural worker employment outcomes.
AB  - BACKGROUND: As access to antiretroviral therapy (ART) has grown in Africa,
      attention has turned to evaluating the socio-economic impacts of ART. One key
      issue is the extent to which improvements in health resulting from ART allows
      individuals to return to work and earn income. Improvements in health from ART
      may also be associated with reduced impaired presenteeism, which is the loss of
      productivity when an ill or disabled individual attends work but accomplishes
      less at his or her usual tasks or shifts to other, possibly less valuable, tasks.
      METHODS: Longitudinal data for this analysis come from company payroll records
      for 97 HIV-infected tea estate workers (the index group, 56 women, 41 men) and a
      comparison group of all workers assigned to the same work teams (n = 2485, 1691
      men, 794 women) for a 37-month period covering two years before and one year
      after initiating ART. We used nearest neighbour matching methods to estimate the
      impacts of HIV/AIDS and ART on three monthly employment outcomes for tea estate
      workers in Kenya--days plucking tea, days assigned to non-plucking assignments,
      and kilograms harvested when plucking. RESULTS: The female index group worked 30%
      fewer days plucking tea monthly than the matched female comparison group during
      the final 9 months pre-ART. They also worked 87% more days on non-plucking
      assignments. While the monthly gap between the two groups narrowed after
      beginning ART, the female index group worked 30% fewer days plucking tea and
      about 100% more days on non-plucking tasks than the comparison group after one
      year on ART. The male index group was able to maintain a similar pattern of work
      as their comparison group except during the initial five months on therapy.
      CONCLUSION: Significant impaired presenteeism continued to exist among the female
      index group after one year on ART. Future research needs to explore further the
      socio-economic implications of HIV-infected female workers on ART being less
      productive than the general female workforce over sustained periods of time.

PMID- 19604382
TI  - Tissue culture-induced transpositional activity of mPing is correlated with
      cytosine methylation in rice.
AB  - BACKGROUND: mPing is an endogenous MITE in the rice genome, which is quiescent
      under normal conditions but can be induced towards mobilization under various
      stresses. The cellular mechanism responsible for modulating the activity of mPing
      remains unknown. Cytosine methylation is a major epigenetic modification in most
      eukaryotes, and the primary function of which is to serve as a genome defense
      system including taming activity of transposable elements (TEs). Given that
      tissue-culture is capable of inducing both methylation alteration and mPing
      transposition in certain rice genotypes, it provides a tractable system to
      investigate the possible relationship between the two phenomena. RESULTS: mPing
      transposition and cytosine methylation alteration were measured in callus and
      regenerated plants in three rice (ssp. indica) genotypes, V14, V27 and R09. All
      three genotypes showed transposition of mPing, though at various frequencies.
      Cytosine methylation alteration occurred both at the mPing-flanks and at random
      loci sampled globally in callus and regenerated plants of all three genotypes.
      However, a sharp difference in the changing patterns was noted between the mPing
      flanks and random genomic loci, with a particular type of methylation
      modification, i.e., CNG hypermethylation, occurred predominantly at the mPing
      flanks. Pearson's test on pairwise correlations indicated that mPing activity is
      positively correlated with specific patterns of methylation alteration at random
      genomic loci, while the element's immobility is positively correlated with
      methylation levels of the mPing's 5'-flanks. Bisulfite sequencing of two mPing
      containing loci showed that whereas for the immobile locus loss of CG methylation
      in the 5'-flank was accompanied by an increase in CHG methylation, together with
      an overall increase in methylation of all three types (CG, CHG and CHH) in the
      mPing-body region, for the active locus erasure of CG methylation in the 5'-flank
      was not followed by such a change. CONCLUSION: Our results documented that tissue
      culture-induced mPing activity in rice ssp. indica is correlated with alteration
      in cytosine methylation patterns at both random genomic loci and the elements'
      flanks, while the stability of mPing positively correlates with enhanced
      methylation levels of both the flanks and probably the elements per se. Thus, our
      results implicate a possible role of cytosine methylation in maintaining mPing
      stability under normal conditions, and in releasing the element's activity as a
      consequence of epigenetic perturbation in a locus-specific manner under certain
      stress conditions.

PMID- 19604383
TI  - Premarital sexual behavior among male college students of Kathmandu, Nepal.
AB  - BACKGROUND: In Nepal, as in other Asian countries, the issue of sexuality still
      remains a taboo. Despite this fact, an increasing number of sexual activities is
      being reported by Nepalese students. This trend warrants serious and timely
      attention. Due to the sensitivity of the topic of premarital sexuality, youth
      receive inadequate education, guidance and services on reproductive health. The
      main objectives of this paper are to explore the sexual behavior especially
      focusing on prevalence of premarital sex among college men and to investigate the
      factors surrounding premarital sexual behavior. METHODS: A cross-sectional survey
      of college students was conducted in April-May 2006. A self-administered
      questionnaire was completed by 573 male students. Association between premarital
      sex and the explanatory variables was assessed in bivariate analysis using Chi
      square tests. The associations were further explored using multivariate logistic
      analysis. RESULTS: Despite the religious and cultural restrictions, about two
      fifths of survey respondents (39%) reported that they have had premarital sex.
      The study has also shown that substantial proportions of students indulge in
      sexual activities as well as risky sexual behavior. Sex with commercial sex
      workers, multiple sex partners, and inconsistence use of condom with non-regular
      partner was common among the students. Less than two in five male students (57%)
      had used condom at the first sexual intercourse.The prevalence of premarital sex
      varied on different settings. Older students aged 20 and above were more likely
      to have premarital sex compared with younger students aged 15-19. Men who had
      liberal attitude towards male virginity at marriage were almost two times more
      likely to have engaged in premarital sex compared to their counterparts who have
      conservative attitude towards male virginity at marriage. Moreover, those
      students who believe in Hindu religion were more than two times (OR = 2.5) more
      likely to have premarital sex compared with those who follow other religions.
      Furthermore, those men who have close unmarried friends who have experienced
      premarital sexual intercourse were eight times (OR = 8.4) more likely to be
      sexually active compared to those who did not have such sexually active friends.
      CONCLUSION: Prevalence of premarital sexual intercourse and risky sexual behavior
      are not uncommon in Nepal. Young people are exposed to health hazards due to
      their sexual behavior; hence sex education should be provided. School or college
      based sexuality education could benefit even out-of-school youths, because their
      partners often are students.

PMID- 19604384
TI  - Food consumption frequency and perceived stress and depressive symptoms among
      students in three European countries.
AB  - BACKGROUND: Certain foods might be more frequently eaten under stress or when
      higher levels of depressive symptoms are experienced. We examined whether poor
      nutritional habits are associated with stress and depressive symptoms and whether
      the relationships differ by country and gender in a sample from three European
      countries collected as part of a Cross National Student Health Survey. METHODS: A
      cross-sectional survey was conducted among first-year students in Germany (N =
      696), Poland (N = 489) and Bulgaria (N = 654). Self-administered questionnaires
      included a 12-item food frequency questionnaire, Cohen's Perceived Stress Scale,
      and a modified Beck Depression Index. Linear regression analyses were conducted
      for two outcomes, perceived stress and depressive symptoms. RESULTS: Food
      consumption frequencies differed by country and gender, as did depressive
      symptoms and perceived stress. For male students, none of the food consumption
      groups were associated with perceived stress or depressive symptoms. In females,
      perceived stress was associated with more frequent consumption of sweets/fast
      foods and less frequent consumption of fruits/vegetables. Additionally,
      depressive symptoms were associated with less frequent consumption of
      fruits/vegetables and meat. CONCLUSION: Our data show consistent associations
      between unhealthy food consumption and depressive symptoms and perceived stress
      among female students from three European countries, but not among male students.
      This suggests that efforts to reduce depressive symptoms and stress among female
      students may also lead to the consumption of healthier foods and/or vice-versa.

PMID- 19604386
TI  - High workload and job stress are associated with lower practice performance in
      general practice: an observational study in 239 general practices in the
      Netherlands.
AB  - BACKGROUND: The impact of high physician workload and job stress on quality and
      outcomes of healthcare delivery is not clear. Our study explored whether high
      workload and job stress were associated with lower performance in general
      practices in the Netherlands. METHODS: Secondary analysis of data from 239
      general practices, collected in practice visits between 2003 to 2006 in the
      Netherlands using a comprehensive set of measures of practice management. Data
      were collected by a practice visitor, a trained non-physician observer using
      patients questionnaires, doctors and staff. For this study we selected five
      measures of practice performance as outcomes and six measures of GP workload and
      job stress as predictors. A total of 79 indicators were used out of the 303
      available indicators. Random coefficient regression models were applied to
      examine associations. RESULTS AND DISCUSSION: Workload and job stress are
      associated with practice performance.Workload: Working more hours as a GP was
      associated with more positive patient experiences of accessibility and
      availability (b = 0.16). After list size adjustment, practices with more GP-time
      per patient scored higher on GP care (b = 0.45). When GPs provided more than 20
      hours per week per 1000 patients, patients scored over 80% on the Europep
      questionnaire for quality of GP care.Job stress: High GP job stress was
      associated with lower accessibility and availability (b = 0.21) and insufficient
      practice management (b = 0.25). Higher GP commitment and more satisfaction with
      the job was associated with more prevention and disease management (b = 0.35).
      CONCLUSION: Providing more time in the practice, and more time per patient and
      experiencing less job stress are all associated with perceptions by patients of
      better care and better practice performance. Workload and job stress should be
      assessed by using list size adjusted data in order to realise better quality of
      care. Organisational development using this kind of data feedback could benefit
      both patients and GP.

PMID- 19604385
TI  - Combination therapy with normobaric oxygen (NBO) plus thrombolysis in
      experimental ischemic stroke.
AB  - BACKGROUND: The widespread use of tissue plasminogen activator (tPA), the only
      FDA-approved acute stroke treatment, remains limited by its narrow therapeutic
      time window and related risks of brain hemorrhage. Normobaric oxygen therapy
      (NBO) may be a useful physiological strategy that slows down the process of
      cerebral infarction, thus potentially allowing for delayed or more effective
      thrombolysis. In this study we investigated the effects of NBO started
      simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected
      to embolic middle cerebral artery (MCA) stroke. After homologous clot injection,
      animals were randomized into different treatment groups: saline injected at 1
      hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was
      maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic
      transformation were quantified at 24 hours. Outcome assessments were blinded to
      therapy. RESULTS: Upon clot injection, cerebral perfusion in the MCA territory
      dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed
      effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct
      volumes (379 +/- 57 mm3 saline controls; 309 +/- 58 mm3 NBO; 201 +/- 78 mm3 tPA;
      138 +/- 30 mm3 tPA plus NBO), showing that tPA-induced reperfusion salvages
      ischemic tissue and that NBO does not significantly alter this neuroprotective
      effect. NBO had no significant effect on hemorrhagic conversion, brain swelling,
      or mortality. CONCLUSION: NBO can be safely co-administered with tPA. The
      efficacy of tPA thrombolysis is not affected and there is no induction of brain
      hemorrhage or edema. These experimental results require clinical confirmation.

PMID- 19604387
TI  - Quality of life following liver transplantation: a comparative study between
      Familial Amyloid Neuropathy and liver disease patients.
AB  - BACKGROUND: It has been demonstrated in many studies that quality of life can be
      improved after liver transplantation in patients with liver disease.
      Nevertheless, quality of life improvement in specific groups of transplanted
      patients such as those with Familial Amyloid Polyneuropathy has not yet been
      explored. The present study aimed to compare the change in quality of life
      following liver transplantation between patients with Familial Amyloid
      Polyneuropathy (FAP) and patients with liver disease. RESULTS: Patient's mental
      quality of life showed an improvement in all liver disease patients, and a
      worsening in FAP patients, resulting in a significant difference between the two
      groups. Regarding physical quality of life, although a similar improvement was
      seen in both groups, FAP patients had significantly less improvement than the sub
      group of decompensated liver disease (Child-Pugh B and C). CONCLUSION: It is
      concluded that liver transplantation has a less beneficial impact in FAP
      patient's physical quality of life, probably because they are not so much
      disabled by their disease at the moment of liver transplantation. The lesser
      improvement in mental quality of life of FAP patients may be due to their
      particular psychological profile and greater expectations towards
      transplantation.

PMID- 19604388
TI  - Breast cancer cells stimulate osteoprotegerin (OPG) production by endothelial
      cells through direct cell contact.
AB  - BACKGROUND: Angiogenesis, the sprouting of capillaries from existing blood
      vessels, is central to tumour growth and progression, however the molecular
      regulation of this process remains to be fully elucidated. The secreted
      glycoprotein osteoprotegerin (OPG) is one potential pro-angiogenic factor, and
      clinical studies have demonstrated endothelial cells within a number of tumour
      types to express high levels of OPG compared to those in normal tissue.
      Additionally, OPG can increase endothelial cell survival, proliferation and
      migration, as well as induce endothelial cell tube formation in vitro. This study
      aims to elucidate the processes involved in the pro-angiogenic effects of OPG in
      vitro, and also how OPG levels may be regulated within the tumour
      microenvironment. RESULTS: It has previously been demonstrated that OPG can
      induce tube formation on growth factor reduced matrigel. In this study, we
      demonstrate that OPG enhances the pro-angiogenic effects of VEGF and that OPG
      does not stimulate endothelial cell tube formation through activation of the
      VEGFR2 receptor. We also show that cell contact between HuDMECs and the T47D
      breast cancer cell line increases endothelial cell OPG mRNA and protein secretion
      levels in in vitro co-cultures. These increases in endothelial cell OPG secretion
      were dependent on alphanubeta3 ligation and NFkappaB activation. In contrast, the
      pro-angiogenic factors VEGF, bFGF and TGFbeta had no effect on HuDMEC OPG levels.
      CONCLUSION: These findings suggest that the VEGF signalling pathway is not
      involved in mediating the pro-angiogenic effects of OPG on endothelial cells in
      vitro. Additionally, we show that breast cancer cells cause increased levels of
      OPG expression by endothelial cells, and that direct contact between endothelial
      cells and tumour cells is required in order to increase endothelial OPG
      expression and secretion. Stimulation of OPG secretion was shown to involve
      alphanubeta3 ligation and NFkappaB activation.

PMID- 19604389
TI  - Assessment of the relative success of sporozoite inoculations in individuals
      exposed to moderate seasonal transmission.
AB  - BACKGROUND: The time necessary for malaria parasite to re-appear in the blood
      following treatment (re-infection time) is an indirect method for evaluating the
      immune defences operating against pre-erythrocytic and early erythrocytic malaria
      stages. Few longitudinal data are available in populations in whom malaria
      transmission level had also been measured. METHODS: One hundred and ten
      individuals from the village of Ndiop (Senegal), aged between one and 72 years,
      were cured of malaria by quinine (25 mg/day oral Quinimax in three equal daily
      doses, for seven days). Thereafter, thick blood films were examined to detect the
      reappearance of Plasmodium falciparum every week, for 11 weeks after treatment.
      Malaria transmission was simultaneously measured weekly by night collection of
      biting mosquitoes. RESULTS: Malaria transmission was on average 15.3 infective
      bites per person during the 77 days follow up. The median reappearance time for
      the whole study population was 46.8 days, whereas individuals would have received
      an average one infective bite every 5 days. At the end of the follow-up, after 77
      days, 103 of the 110 individuals (93.6%; CI 95% [89.0-98.2]) had been re-infected
      with P. falciparum. The median reappearance time ('re-positivation') was longer
      in subjects with patent parasitaemia at enrolment than in parasitologically
      negative individuals (58 days vs. 45.9; p = 0.03) and in adults > 30 years than
      in younger subjects (58.6 days vs. 42.7; p = 0.0002). In a multivariate Cox PH
      model controlling for the sickle cell trait, G6PD deficiency and the type of
      habitat, the presence of parasitaemia at enrolment and age >/= 30 years were
      independently predictive of a reduced risk of re-infection (PH = 0.5 [95% CI: 0.3
      0.9] and 0.4; [95% CI: 0.2-0.6] respectively). CONCLUSION: Results indicate the
      existence of a substantial resistance to sporozoites inoculations, but which was
      ultimately overcome in almost every individual after 2 1/2 months of natural
      challenges. Such a study design and the results obtained suggest that, despite a
      small sample size, this approach can contribute to assess the impact of
      intervention methods, such as the efficacy vector-control measures or of malaria
      pre-erythrocytic stages vaccines.

PMID- 19604391
TI  - Linked region detection using high-density SNP genotype data via the minimum
      recombinant model of pedigree haplotype inference.
AB  - BACKGROUND: With the rapid development of high-throughput genotyping
      technologies, efficient methods for identifying linked regions using high-density
      SNP genotype data have become more and more important. Recently, a deterministic
      method that works very well on SNP genotyping data has been developed (Lin et al.
      Bioinformatics 2008, 24(1): 86-93). However, that program can only work on a
      limited number of family structures. In particular, the results (if any) will be
      poor when the genotype data for the whole chromosome of one of the parents in a
      nuclear family is missing. RESULTS: We have developed a software package (LIden)
      for identifying linked regions using high-density SNP genotype data. We focus on
      handling the case where the genotype data for the whole chromosome of one of the
      parents in a nuclear family is missing. We use the minimum recombinant model for
      haplotype inference in pedigrees. Several local optimization algorithms are used
      to infer the haplotype of each individual and determine the linked regions based
      on the inferred haplotype data. We have developed a more flexible method to
      combine nuclear families to further refine (reduce the length of) the linked
      regions. CONCLUSION: Our new package (LIden) is efficient software for linked
      region detection using high-density SNP genotype data. LIden can handle some
      important cases where the existing programs do not work well. In particular, the
      new package can handle many cases where the genotype data of one of the two
      parents is missing for the entire chromosome. The running time of the program is
      O(mn), where m is the number of members in the family and n is the number of SNP
      sites in the chromosome. LIden is specifically suitable for handling big sized
      families. This research also demonstrates another practical use of the minimum
      recombinant model for haplotype inference in pedigrees. The software package can
      be downloaded at http://www.cs.cityu.edu.hk/~lwang/software/Link.

PMID- 19604390
TI  - Characterization of MCF mammary epithelial cells overexpressing the
      Arylhydrocarbon receptor (AhR).
AB  - BACKGROUND: Recent reports indicate the existence of breast cancer cells
      expressing very high levels of the Arylhydrocarbon receptor (AhR), a ubiquitous
      intracellular receptor best known for mediating toxic action of dioxin and
      related pollutants. Positive correlation between the degree of AhR overexpression
      and states of increasing transformation of mammary epithelial cells appears to
      occur in the absence of any exogenous AhR ligands. These observations have raised
      many questions such as why and how AhR is overexpressed in breast cancer and its
      physiological roles in the progression to advanced carcinogenic transformation.
      To address those questions, we hypothesized that AhR overexpression occurs in
      cells experiencing deficiencies in normally required estrogen receptor (ER)
      signaling, and the basic role of AhR in such cases is to guide the affected cells
      to develop orchestrated cellular changes aimed at substituting the normal
      functions of ER. At the same time, the AhR serves as the mediator of the cell
      survival program in the absence of ER signaling. METHODS: We subjected two lines
      of Michigan Cancer Foundation (MCF) mammary epithelial cells to 3 different types
      ER interacting agents for a number of passages and followed the changes in the
      expression of AhR mRNA. The resulting sublines were analyzed for phenotypical
      changes and unique molecular characteristics. RESULTS: MCF10AT1 cells
      continuously exposed to 17-beta-estradiol (E2) developed sub-lines that show AhR
      overexpression with the characteristic phenotype of increased proliferation, and
      distinct resistance to apoptosis. When these chemically selected cell lines were
      treated with a specific AhR antagonist, 3-methoxy-4-nitroflavone (MNF), both of
      the above abnormal cellular characteristics disappeared, indicating the pivotal
      role of AhR in expressing those cellular phenotypes. The most prominent molecular
      characteristics of these AhR overexpressing MCF cells were found to be
      overexpression of ErbB2 and COX-2. Furthermore, we could demonstrate that
      suppression of AhR functions through anti-AhR siRNA or MNF causes the recovery of
      ERalpha functions. CONCLUSION: One of the main causes for AhR overexpression in
      these MCF breast cancer cells appears to be the loss of ERalpha functions. This
      phenomenon is likely to be based on the mutually antagonistic relationship
      between ER and AhR.

PMID- 19604392
TI  - A pilot study evaluating a support programme for parents of young people with
      suicidal behaviour.
AB  - BACKGROUND: Deliberate self harm (DSH) is a major public health concern and has
      increased among young people in Ireland. While DSH is undoubtedly the result of
      interacting factors, studies have identified an association between DSH and
      family dysfunction as well as the protective role of positive family
      relationships. Following a focus group meeting held to identify the needs of
      parents and carers of young people with DSH, a support programme (SPACE) was
      developed. The aims of the current study are to evaluate the effectiveness of the
      SPACE programme in decreasing parental psychological distress, reducing parental
      report of young peoples' difficulties, increasing parental satisfaction and
      increasing parents' ratings of their own defined challenges and goals. METHODS:
      Participants were recruited from a Mental Health Service within a paediatric
      hospital, Community Child and Adolescent Mental Health Teams and family support
      services. All services were located within the greater Dublin area in Ireland.
      Forty-six parents of children who had engaged in or expressed thoughts of self
      harm attended the programme and participated in the evaluation study. The
      programme ran once a week over an 8-week period and included topics such as
      information on self harm in young people, parenting adolescents, communication
      and parental self-care. Seventy percent (N = 32) of the original sample at Time 1
      completed measures at Time 2 (directly following the programme) and 37% (N = 17)
      of the original sample at Time 1 completed them at Time 3 (6 months following the
      programme). A repeated measures design was used to identify changes in parental
      wellbeing after attendance at the programme as well as changes in parental
      reports of their children's difficulties. RESULTS: Participants had lower levels
      of psychological distress, increased parental satisfaction, lower ratings of
      their own defined challenges and higher ratings of their goals directly after the
      programme. These changes were maintained at 6-month follow up in the 37% of
      participants who could be followed up. Furthermore the young people who had
      engaged in or expressed thoughts of self harm had lower levels of difficulties,
      as reported by their parents, following the programme. CONCLUSION: These findings
      suggest that the SPACE programme is a promising development in supporting the
      parents of young people with suicidal behaviour. The programme may also reduce
      parental reports of their children's difficulties. Further evaluation using a
      randomized controlled trial is indicated.

PMID- 19604393
TI  - Uncovering the Arabidopsis thaliana nectary transcriptome: investigation of
      differential gene expression in floral nectariferous tissues.
AB  - BACKGROUND: Many flowering plants attract pollinators by offering a reward of
      floral nectar. Remarkably, the molecular events involved in the development of
      nectaries, the organs that produce nectar, as well as the synthesis and secretion
      of nectar itself, are poorly understood. Indeed, to date, no genes have been
      shown to directly affect the de novo production or quality of floral nectar. To
      address this gap in knowledge, the ATH1 Affymetrix GeneChip array was used to
      systematically investigate the Arabidopsis nectary transcriptome to identify
      genes and pathways potentially involved in nectar production. RESULTS: In this
      study, we identified a large number of genes differentially expressed between
      secretory lateral nectaries and non-secretory median nectary tissues, as well as
      between mature lateral nectaries (post-anthesis) and immature lateral nectaries
      (pre-anthesis). Expression within nectaries was also compared to thirteen non
      nectary reference tissues, from which 270 genes were identified as being
      significantly upregulated in nectaries. The expression patterns of 14 nectary
      enriched genes were also confirmed via RT PCR. Upon looking into functional
      groups of upregulated genes, pathways involved in gene regulation, carbohydrate
      metabolism, and lipid metabolism were particularly enriched in nectaries versus
      reference tissues. CONCLUSION: A large number of genes preferentially expressed
      in nectaries, as well as between nectary types and developmental stages, were
      identified. Several hypotheses relating to mechanisms of nectar production and
      regulation thereof are proposed, and provide a starting point for reverse
      genetics approaches to determine molecular mechanisms underlying nectar synthesis
      and secretion.

PMID- 19604395
TI  - Size-exclusion chromatography can identify faster-associating protein complexes
      and evaluate design strategies.
AB  - BACKGROUND: We previously developed a set of rationally designed mutant MICA
      protein ligands for the NKG2D immunoreceptor in which MICA was mutated at
      residues that do not contact NKG2D. Some of these MICA mutants, predicted by
      RosettaDesign to be destabilized, bound NKG2D with affinities enhanced by more
      than an order of magnitude when evaluated by surface plasmon resonance (SPR).
      FINDINGS: Small-zone size-exclusion chromatography (SEC) detected persistent high
      affinity MICA mutant-NKG2D complexes in solution as early-eluting peaks. The SEC
      binding assay used standard protein purification instrumentation to evaluate
      complex stability, qualitatively paralleled the SPR results, and successfully
      discriminated among complexes that differed only in on-rates. We used the SEC
      binding assay, along with SPR, to assess the results of a follow-up design
      strategy targeting the non-interfacial redesigned region. Both SEC and SPR agreed
      that these mutations did not enhance affinity as much as previous mutants. When
      the SEC binding assay was run in 1 M urea, only the highest affinity complex was
      detected. CONCLUSION: This SEC binding assay provides a correlation with SPR
      results for protein complex affinities, detecting changes in complex on-rates,
      and tunable to lower sensitivity with 1 M urea. The SEC binding assay is
      complementary to other protein design evaluation methods, can be adapted to the
      undergraduate research laboratory, and may provide additional structural
      information about changes in hydrodynamic radii from elution times. Our assay
      allowed us to conclude that further alteration of MICA at non-contacting residues
      is unlikely to further enhance NKG2D affinity.

PMID- 19604394
TI  - Sperm protein 17 is expressed in the sperm fibrous sheath.
AB  - BACKGROUND: Sperm protein 17 (Sp17) is a highly conserved mammalian protein
      characterized in rabbit, mouse, monkey, baboon, macaque, human testis and
      spermatozoa. mRNA encoding Sp17 has been detected in a range of murine and human
      somatic tissues. It was also recognized in two myeloma cell lines and in
      neoplastic cells from patients with multiple myeloma and ovarian carcinoma. These
      data all indicate that Sp17 is widely distributed in humans, expressed not only
      in germinal cells and in a variety of somatic tissues, but also in neoplastic
      cells of unrelated origin. METHODS: Sp17 expression was analyzed by
      immunocytochemistry and transmission electron microscopy on spermatozoa. RESULTS:
      Here, we demonstrate the ultrastructural localization of human Sp17 throughout
      the spermatozoa flagellar fibrous sheath, and its presence in spermatozoa during
      in vitro states from their ejaculation to the oocyte fertilization. CONCLUSION:
      These findings suggest a possible role of Sp17 in regulating sperm maturation,
      capacitation, acrosomal reaction and interactions with the oocyte zona pellucida
      during the fertilization process. Further, the high degree of sequence
      conservation throughout its N-terminal half, and the presence of an A-kinase
      anchoring protein (AKAP)-binding motif within this region, suggest that Sp17
      might play a regulatory role in a protein kinase A-independent AKAP complex in
      both germinal and somatic cells.

PMID- 19604396
TI  - Antimicrobial activity of a C-terminal peptide from human extracellular
      superoxide dismutase.
AB  - BACKGROUND: Antimicrobial peptides (AMP) are important effectors of the innate
      immune system. Although there is increasing evidence that AMPs influence bacteria
      in a multitude of ways, bacterial wall rupture plays the pivotal role in the
      bactericidal action of AMPs. Structurally, AMPs share many similarities with
      endogenous heparin-binding peptides with respect to secondary structure,
      cationicity, and amphipathicity. FINDINGS: In this study, we show that RQA21
      (RQAREHSERKKRRRESECKAA), a cationic and hydrophilic heparin-binding peptide
      corresponding to the C-terminal region of extracellular superoxide dismutase
      (SOD), exerts antimicrobial activity against Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus, Bacillus subtilis and Candida albicans. The
      peptide was also found to induce membrane leakage of negatively charged
      liposomes. However, its antibacterial effects were abrogated in physiological
      salt conditions as well as in plasma. CONCLUSION: The results provide further
      evidence that heparin-binding peptide regions are multifunctional, but also
      illustrate that cationicity alone is not sufficient for AMP function at
      physiological conditions. However, our observation, apart from providing a link
      between heparin-binding peptides and AMPs, raises the hypothesis that
      proteolytically generated C-terminal SOD-derived peptides could interact with,
      and possibly counteract bacteria. Further studies are therefore merited to study
      a possible role of SOD in host defence.

PMID- 19604398
TI  - The role of a pseudocapsula in thymic epithelial tumors: outcome and correlation
      with established prognostic parameters. Results of a 20-year single centre
      retrospective analysis.
AB  - BACKGROUND: Treatment of thymoma is often based on observation of only a few
      patients. Surgical resection is considered to be the most important step. Role of
      a pseudocapsula for surgery, its clinical significance and outcome compared with
      established prognostic parameters is discussed which has not been reported so
      far. METHODS: 84 patients with thymoma underwent resection and analysis was
      carried out for clinical features, prognostic factors and long-term survival.
      RESULTS: Fifteen patients were classified in WHO subgroup A, 21 in AB, 29 in B
      and 19 patients in C. Forty two patients were classified in Masaoka stage I, 19
      stage II, 9 stage III and 14 stage IV. Encapsulated thymoma was seen in 40,
      incomplete or missing capsula in 44 patients. In 71 complete resections, local
      recurrence was 5%. 5-year survival was 88.1%. Thymomas with pseudocapsula showed
      a significant better survival (94.9% vs. 61.1%, respectively) (p = 0.001) and was
      correlated with the absence of nodal or distant metastasis (p = 0.04 and 0.001,
      respectively). Presence of pseudocapsula as well as the Masaoka and WHO
      classification, and R-status were of prognostic significance. R-status and
      Masaoka stage appeared to be of independent prognostic significance in
      multivariate analysis. CONCLUSION: Intraoperative presence of an encapsulated
      tumor is a good technical marker for the surgeon to evaluate resectability and
      estimate prognosis. Although the presence of a capsula is of strong significance
      in the univariate analysis, it failed in the multivariate analysis due to its
      correlation with clinical Masaoka stage. Masaoka stage has a stronger relevance
      than WHO classification to determinate long-term outcome.

PMID- 19604397
TI  - Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin
      depolymerisation, focal contact size reduction and Snail1 induction - a model for
      cross-modulation.
AB  - BACKGROUND: A feature of epithelial to mesenchymal transition (EMT) relevant to
      tumour dissemination is the reorganization of actin cytoskeleton/focal contacts,
      influencing cellular ECM adherence and motility. This is coupled with the
      transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and
      Zeb1/deltaEF1. These genes, overexpressed in breast carcinomas, are known targets
      of growth factor-initiated pathways, however it is less clear how alterations in
      ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the
      breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST)
      induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and
      disruption of cell-cell adhesion, via inhibition of aPKC. METHODS: PMC42-LA cells
      were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for
      expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/deltaEF1) and EMT
      related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/
      cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal
      microscopy. A public database of human breast cancers was assessed for expression
      of Snail1 and Snail2 in relation to outcome. RESULTS: When PMC42-LA were treated
      with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or
      ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/deltaEF1 induction
      seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and
      independently of gene transcription. Gene expression analysis by MT-PCR indicated
      that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61,
      CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2,
      EPHB4). Examination of the public database of breast cancers revealed tumours
      exhibiting higher Snail1 expression have an increased risk of disease-recurrence.
      This was not seen for Snail2, and Zeb1/deltaEF1 showed a reverse correlation with
      lower expression values being predictive of increased risk. CONCLUSION: ST in
      combination with EGF directed a greater EMT via actin depolymerisation and focal
      contact size reduction, resulting in a loosening of cell-ECM attachment along
      with Snail1-Zeb1/deltaEF1 induction. This appeared fundamentally different to the
      EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our
      findings add support for a functional role for Snail1 in invasive breast cancer.

PMID- 19604399
TI  - Validity and reliability of a new, short symptom rating scale in patients with
      persistent atrial fibrillation.
AB  - BACKGROUND: Symptoms related to atrial fibrillation and their impact on health
      related quality of life (HRQoL) are often evaluated in clinical trials. However,
      there remains a need for a properly validated instrument. We aimed to develop and
      validate a short symptoms scale for patients with AF. METHODS: One hundred and
      eleven patients with a variety of symptoms related to AF were scheduled for DC
      cardioversion. The mean age was 67.1 +/- 12.1 years, and 80% were men. The
      patients completed the new symptoms scale, the Toronto Symptoms Check List (SCL)
      and the generic Short Form 36 (SF-36) the day before the planned DC
      cardioversion. Compliance was excellent, with only 1 of 666 answers missing.
      RESULTS: One item, 'limitations in working capability', was deleted because of a
      low numerical response rate, as many of the patients were retired. The internal
      consistency reliability of the remaining six items was 0.81 (Cronbach's alpha).
      Patients scored highest in the items of 'dyspnoea on exertion', 'limitations in
      daily life due to AF' and 'fatigue due to AF', with scores of 4.5, 3.3 and 4.5,
      respectively. There was a good correlation to all relevant SF-36 domains and to
      the relevant questions of the SCL. The Rasch analyses showed that the items are
      unidimensional and that they are clearly separated and cover an adequate range.
      Test-retest reliability was performed in patients who failed DC and was adequate
      for three of six items, > 0.70. CONCLUSION: The psychometric characteristics of
      the new short symptoms scale were found to have satisfactory reliability and
      validity.

PMID- 19604400
TI  - A compartmentalized approach to the assembly of physical maps.
AB  - BACKGROUND: Physical maps have been historically one of the cornerstones of
      genome sequencing and map-based cloning strategies. They also support marker
      assisted breeding and EST mapping. The problem of building a high quality
      physical map is computationally challenging due to unavoidable noise in the input
      fingerprint data. RESULTS: We propose a novel compartmentalized method for the
      assembly of high quality physical maps from fingerprinted clones. The knowledge
      of genetic markers enables us to group clones into clusters so that clones in the
      same cluster are more likely to overlap. For each cluster of clones, a local
      physical map is first constructed using FingerPrinted Contigs (FPC). Then, all
      the individual maps are carefully merged into the final physical map.
      Experimental results on the genomes of rice and barley demonstrate that the
      compartmentalized assembly produces significantly more accurate maps, and that it
      can detect and isolate clones that would induce "chimeric" contigs if used in the
      final assembly. CONCLUSION: The software is available for download at
      http://www.cs.ucr.edu/~sbozdag/assembler/

PMID- 19604401
TI  - Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl
      Terminal Modulator Protein.
AB  - BACKGROUND: The serine/threonine protein kinase B (PKB/Akt) is involved in
      insulin signaling, cellular survival, and transformation. Carboxyl-terminal
      modulator protein (CTMP) has been identified as a novel PKB binding partner in a
      yeast two-hybrid screen, and appears to be a negative PKB regulator with tumor
      suppressor-like properties. In the present study we investigate novel mechanisms
      by which CTMP plays a role in apoptosis process. RESULTS: CTMP is localized to
      mitochondria. Furthermore, CTMP becomes phosphorylated following the treatment of
      cells with pervanadate, an insulin-mimetic. Two serine residues (Ser37 and Ser38)
      were identified as novel in vivo phosphorylation sites of CTMP. Association of
      CTMP and heat shock protein 70 (Hsp70) inhibits the formation of complexes
      containing apoptotic protease activating factor 1 and Hsp70. Overexpression of
      CTMP increased the sensitivity of cells to apoptosis, most likely due to the
      inhibition of Hsp70 function. CONCLUSION: Our data suggest that phosphorylation
      on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial
      localization of CTMP, eventually leading to cell death by binding to Hsp70. In
      addition to its role in PKB inhibition, CTMP may therefore play a key role in
      mitochondria-mediated apoptosis by localizing to mitochondria.

PMID- 19604402
TI  - Methods of estimation of mitral valve regurgitation for the cardiac surgeon.
AB  - Mitral valve regurgitation is a relatively common and important heart valve
      lesion in clinical practice and adequate assessment is fundamental to decision on
      management, repair or replacement. Disease localised to the posterior mitral
      valve leaflet or focal involvement of the anterior mitral valve leaflet is most
      amenable to mitral valve repair, whereas patients with extensive involvement of
      the anterior leaflet or incomplete closure of the valve are more suitable for
      valve replacement. Echocardiography is the recognized investigation of choice for
      heart valve disease evaluation and assessment. However, the technique is depended
      on operator experience and on patient's hemodynamic profile, and may not always
      give optimal diagnostic views of mitral valve dysfunction. Cardiac
      catheterization is related to common complications of an interventional procedure
      and needs a hemodynamic laboratory. Cardiac magnetic resonance (MRI) seems to be
      a useful tool which gives details about mitral valve anatomy, precise point of
      valve damage, as well as the quantity of regurgitation. Finally, despite of its
      higher cost, cardiac MRI using cine images with optimized spatial and temporal
      resolution can also resolve mitral valve leaflet structural motion, and can
      reliably estimate the grade of regurgitation.

PMID- 19604403
TI  - NG2 and phosphacan are present in the astroglial scar after human traumatic
      spinal cord injury.
AB  - BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS
      scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs).
      Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of
      CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in
      such lesion models results in substantially enhanced axonal regeneration and a
      significant functional recovery. The potential therapeutic relevance of
      interfering with CSPG expression or function following experimental injuries
      seems clear, however, the spatio-temporal pattern of expression of individual
      members of the CSPG family following human spinal cord injury is only poorly
      defined. In the present correlative investigation, the expression pattern of CSPG
      family members NG2, neurocan, versican and phosphacan was studied in the human
      spinal cord. METHODS: An immunohistochemical investigation in post mortem samples
      of control and lesioned human spinal cords was performed. All patients with
      traumatic SCI had been clinically diagnosed as having "complete" injuries and
      presented lesions of the maceration type. RESULTS: In sections from control
      spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells
      corresponding to oligodendrocyte precursor cells. The distribution patterns of
      phosphacan, neurocan and versican in control human spinal cord parenchyma were
      similar, with a fine reticular pattern being observed in white matter (but also
      located in gray matter for phosphacan). Neurocan staining was also associated
      with blood vessel walls. Furthermore, phosphacan, neurocan and versican were
      present in the myelin sheaths of ventral and dorsal nerve roots axons. After
      human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar.
      Neurocan and versican were detected exclusively in the lesion epicentre, being
      associated with infiltrating Schwann cells in the myelin sheaths of invading
      peripheral nerve fibres from lesioned dorsal roots. CONCLUSION: NG2 and
      phosphacan were both present in the evolving astroglial scar and, therefore,
      might play an important role in the blockade of successful CNS regeneration.
      Neurocan and versican, however, were located at the lesion epicentre, associated
      with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution
      that was unlikely to contribute to failed CNS axon regeneration. The present data
      points to the importance of such correlative investigations for demonstrating the
      clinical relevance of experimental data.

PMID- 19604404
TI  - The caudal regeneration blastema is an accumulation of rapidly proliferating stem
      cells in the flatworm Macrostomum lignano.
AB  - BACKGROUND: Macrostomum lignano is a small free-living flatworm capable of
      regenerating all body parts posterior of the pharynx and anterior to the brain.
      We quantified the cellular composition of the caudal-most body region, the tail
      plate, and investigated regeneration of the tail plate in vivo and in semithin
      sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S
      phase. RESULTS: The tail plate accomodates the male genital apparatus and
      consists of about 3,100 cells, about half of which are epidermal cells. A
      distinct regeneration blastema, characterized by a local accumulation of rapidly
      proliferating neoblasts and consisting of about 420 cells (excluding epidermal
      cells), was formed 24 hours after amputation. Differentiated cells in the
      blastema were observed two days after amputation (with about 920 blastema cells),
      while the male genital apparatus required four to five days for full
      differentiation. At all time points, mitoses were found within the blastema. At
      the place of organ differentiation, neoblasts did not replicate or divide. After
      three days, the blastema was made of about 1420 cells and gradually transformed
      into organ primordia, while the proliferation rate decreased. The cell number of
      the tail plate, including about 960 epidermal cells, was restored to 75% at this
      time point. CONCLUSION: Regeneration after artificial amputation of the tail
      plate of adult specimens of Macrostomum lignano involves wound healing and the
      formation of a regeneration blastema. Neoblasts undergo extensive proliferation
      within the blastema. Proliferation patterns of S-phase neoblasts indicate that
      neoblasts are either determined to follow a specific cell fate not before, but
      after going through S-phase, or that they can be redetermined after S-phase. In
      pulse-chase experiments, dispersed distribution of label suggests that S-phase
      labeled progenitor cells of the male genital apparatus undergo further
      proliferation before differentiation, in contrast to progenitor cells of
      epidermal cells. Mitotic activity and proliferation within the blastema is a
      feature of M. lignano shared with many other regenerating animals.

PMID- 19604405
TI  - Ethnic differences in the adaptation rate of HIV gp120 from a vaccine trial.
AB  - Differences in HIV-1 gp120 sequence variation were examined in North American
      volunteers who became infected during a phase III vaccine trial using the rgp120
      vaccine. Molecular adaptation of the virus in vaccine and placebo recipients from
      different ethnic subgroups was compared by estimating the dN/dS ratios in viruses
      sampled from each individual using three different methods. ANOVA analyses
      detected significant differences in d(N)/d(S) ratios among races (P < 0.02).
      gp120 sequences from the black individuals showed higher mean d(N)/d(S) ratios
      for all estimators (1.24-1.45) than in other races (0.66-1.35), and several
      pairwise comparisons involving blacks remained significant (P < 0.05) after
      correction for multiple tests. In addition, black-placebo individuals showed
      significantly (P < 0.02) higher mean d(N)/d(S) ratios (1.3-1.66) than placebo
      individuals from the other races (0.65-1.56). These results suggest intrinsic
      differences among races in immune response and highlight the need for including
      multiple ethnicities in the design of future HIV-1 vaccine studies and trials.

PMID- 19604408
TI  - Effectiveness and cost of recruitment strategies for a community-based randomised
      controlled trial among rainwater drinkers.
AB  - BACKGROUND: Community-based recruitment is challenging particularly if the
      sampling frame is not easily defined as in the case of people who drink
      rainwater. Strategies for contacting participants must be carefully considered to
      maximise generalisability and minimise bias of the results. This paper assesses
      the recruitment strategies for a 1-year double-blinded randomised trial on
      drinking untreated rainwater. The effectiveness of the recruitment strategies and
      associated costs are described. METHODS: Community recruitment of households from
      Adelaide, Australia occurred from February to July 2007 using four methods:
      electoral roll mail-out, approaches to schools and community groups, newspaper
      advertising, and other media involvement. Word of mouth communication was also
      assessed. RESULTS: A total of 810 callers were screened, with 53.5% eligible. Of
      those who were eligible and sent further information, 76.7% were willing to
      participate in the study and 75.1% were enrolled. The target for recruitment was
      300 households, and this was achieved. The mail-out was the most effective method
      with respect to number of households randomised, while recruitment via schools
      had the highest yield (57.3%) and was the most cost effective when considering
      cost per household randomised (AUD$147.20). Yield and cost effectiveness were
      lowest for media advertising. CONCLUSION: The use of electoral roll mail-out and
      advertising via schools were effective in reaching households using untreated
      rainwater for drinking. Employing multiple strategies enabled success in
      achieving the recruitment target. In countries where electoral roll extracts are
      available to researchers, this method is likely to have a high yield for
      recruitment into community-based epidemiological studies.

PMID- 19604406
TI  - Proviral integrations and expression of endogenous avian leucosis virus during
      long term selection for high and low body weight in two chicken lines.
AB  - BACKGROUND: Long-term selection (> 45 generations) for low or high juvenile body
      weight from a common founder population of White Plymouth Rock chickens has
      generated two extremely divergent lines, the LWS and HWS lines. In addition to a
      > 9-fold difference between lines for the selected trait, large behavioural and
      metabolic differences between the two lines evolved during the course of the
      selection. We recently compared gene expression in brain tissue from birds
      representing these lines using a global cDNA array analysis and the results
      showed multiple but small expression differences in protein coding genes. The
      main differentially expressed transcripts were endogenous retroviral sequences
      identified as avian leucosis virus subgroup-E (ALVE). RESULTS: In this work we
      confirm the differential ALVE expression and analysed expression and number of
      proviral integrations in the two parental lines as well as in F9 individuals from
      an advanced intercross of the lines. Correlation analysis between expression,
      proviral integrations and body weight showed that high ALVE levels in the LWS
      line were inherited and that more ALVE integrations were detected in LWS than HWS
      birds. CONCLUSION: We conclude that only a few of the integrations contribute to
      the high expression levels seen in the LWS line and that high ALVE expression was
      significantly correlated with lower body weights for the females but not males.
      The conserved correlation between high expression and low body weight in females
      after 9 generations of intercrosses, indicated that ALVE loci conferring high
      expression directly affects growth or are very closely linked to loci regulating
      growth.

PMID- 19604409
TI  - Structural analysis of three novel trisaccharides isolated from the fermented
      beverage of plant extracts.
AB  - BACKGROUND: A fermented beverage of plant extracts was prepared from about fifty
      kinds of vegetables and fruits. Natural fermentation was carried out mainly by
      lactic acid bacteria (Leuconostoc spp.) and yeast (Zygosaccharomyces spp. and
      Pichia spp.). We have previously examined the preparation of novel four
      trisaccharides from the beverage: O-beta-D-fructopyranosyl-(2->6)-O-beta-D
      glucopyranosyl-(1->3)-D-glucopyranose, O-beta-D-fructopyranosyl-(2->6)-O-[beta-D
      glucopyranosyl-(1->3)]-D-glucopyranose, O-beta-D-glucopyranosyl-(1->1)-O-beta-D
      fructofuranosyl-(2<->1)-alpha-D-glucopyranoside and O-beta-D-galactopyranosyl-(1
      >1)-O-beta-D-fructofuranosyl-(2<->1)- alpha-D-glucopyranoside. RESULTS: Three
      further novel oligosaccharides have been found from this beverage and isolated
      from the beverage using carbon-Celite column chromatography and preparative high
      performance liquid chromatography. Structural confirmation of the saccharides was
      provided by methylation analysis, MALDI-TOF-MS and NMR measurements. CONCLUSION:
      The following novel trisaccharides were identified: O-beta-D-fructofuranosyl-(2
      >1)-O-[beta-D-glucopyranosyl-(1->3)]-beta-D-glucopyranoside (named "3G-beta-D
      glucopyranosyl beta, beta-isosucrose"), O-beta-D-glucopyranosyl-(1->2)-O-[beta-D
      glucopyranosyl-(1->4)]-D-glucopyranose (4(1)-beta-D-glucopyranosyl sophorose) and
      O-beta-D-fructofuranosyl-(2->6)-O-beta-D-glucopyranosyl-(1->3)-D-glucopyranose
      (6(2)-beta-D-fructofuranosyl laminaribiose).

PMID- 19604407
TI  - Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2
      diabetes: a randomized cross-over pilot study.
AB  - BACKGROUND: Our aim was to compare the effects of a Paleolithic ('Old Stone Age')
      diet and a diabetes diet as generally recommended on risk factors for
      cardiovascular disease in patients with type 2 diabetes not treated with insulin.
      METHODS: In a randomized cross-over study, 13 patients with type 2 diabetes, 3
      women and 10 men, were instructed to eat a Paleolithic diet based on lean meat,
      fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet
      designed in accordance with dietary guidelines during two consecutive 3-month
      periods. Outcome variables included changes in weight, waist circumference, serum
      lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and
      areas under the curve for plasma glucose and plasma insulin in the 75 g oral
      glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food
      records. RESULTS: Study participants had on average a diabetes duration of 9
      years, a mean HbA1c of 6,6% units by Mono-S standard and were usually treated
      with metformin alone (3 subjects) or metformin in combination with a sulfonylurea
      (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin
      was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted
      in lower mean values of HbA1c (-0.4% units, p = 0.01), triacylglycerol (-0.4
      mmol/L, p = 0.003), diastolic blood pressure (-4 mmHg, p = 0.03), weight (-3 kg,
      p = 0.01), BMI (-1 kg/m2, p = 0.04) and waist circumference (-4 cm, p = 0.02),
      and higher mean values of high density lipoprotein cholesterol (+0.08 mmol/L, p =
      0.03). The Paleolithic diet was mainly lower in cereals and dairy products, and
      higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet.
      Further, the Paleolithic diet was lower in total energy, energy density,
      carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and
      higher in unsaturated fatty acids, dietary cholesterol and several vitamins.
      Dietary GI was slightly lower in the Paleolithic diet (GI = 50) than in the
      Diabetic diet (GI = 55). CONCLUSION: Over a 3-month study period, a Paleolithic
      diet improved glycemic control and several cardiovascular risk factors compared
      to a Diabetes diet in patients with type 2 diabetes.

PMID- 19604410
TI  - Intra-arterial delivery of triolein emulsion increases vascular permeability in
      skeletal muscles of rabbits.
AB  - BACKGROUND: To test the hypothesis that triolein emulsion will increase vascular
      permeability of skeletal muscle. METHODS: Triolein emulsion was infused into the
      superficial femoral artery in rabbits (triolein group, n = 12). As a control,
      saline was infused (saline group, n = 18). Pre- and post-contrast T1-weighted MR
      images were obtained two hours after infusion. The MR images were qualitatively
      and quantitatively evaluated by assessing the contrast enhancement of the
      ipsilateral muscles. Histologic examination was performed in all rabbits.
      RESULTS: The ipsilateral muscles of the rabbits in the triolein group showed
      contrast enhancement, as opposed to in the ipsilateral muscles of the rabbits in
      the saline group. The contrast enhancement of the lesions was statistically
      significant (p < 0.001). Histologic findings showed that most examination areas
      of the triolein and saline groups had a normal appearance. CONCLUSION: Rabbit
      thigh muscle revealed significantly increased vascular permeability with triolein
      emulsion; this was clearly demonstrated on the postcontrast MR images.

PMID- 19604411
TI  - The formation of acetylcholine receptor clusters visualized with quantum dots.
AB  - BACKGROUND: Motor innervation of skeletal muscle leads to the assembly of
      acetylcholine receptor (AChR) clusters in the postsynaptic membrane at the
      vertebrate neuromuscular junction (NMJ). Synaptic AChR aggregation, according to
      the diffusion-mediated trapping hypothesis, involves the establishment of a
      postsynaptic scaffold that "traps" freely diffusing receptors into forming high
      density clusters. Although this hypothesis is widely cited to explain the
      formation of postsynaptic AChR clusters, direct evidence at molecular level is
      lacking. RESULTS: Using quantum dots (QDs) and live cell imaging, we provide new
      measurements supporting the diffusion-trap hypothesis as applied to AChR cluster
      formation. Consistent with published works, experiments on cultured Xenopus
      myotomal muscle cells revealed that AChRs at clusters that formed spontaneously
      (pre-patterned clusters, also called hot spots) and at those induced by nerve
      innervation or by growth factor-coated latex beads were very stable whereas
      diffuse receptors outside these regions were mobile. Moreover, despite the
      restriction of AChR movement at sites of synaptogenic stimulation, individual
      receptors away from these domains continued to exhibit free diffusion, indicating
      that AChR clustering at NMJ does not involve an active attraction of receptors
      but is passive and diffusion-driven. CONCLUSION: Single-molecular tracking using
      QDs has provided direct evidence that the clustering of AChRs in muscle cells in
      response to synaptogenic stimuli is achieved by two distinct cellular processes:
      the Brownian motion of receptors in the membrane and their trapping and
      immobilization at the synaptic specialization. This study also provides a clearer
      picture of the "trap" that it is not a uniformly sticky area but consists of
      discrete foci at which AChRs are immobilized.

PMID- 19604413
TI  - Complex hydrocephalus (combination of communicating and obstructive type): an
      important cause of failed endoscopic third ventriculostomy.
AB  - BACKGROUND: Hydrocephalus can be classified as purely obstructive, purely
      communicating or due to combinations of pathologies (obstruction in addition to
      defective absorption). Endoscopic third ventriculostomy (ETV) as an alternative
      to shunt procedures is an established treatment for obstructive hydrocephalus.
      However, patients who have combination of pathologies (complex hydrocephalus)
      could result in failure of ETV in spite of a patent stoma. The aim of this study
      was to prospectively evaluate the incidence of complex hydrocephalus in patients
      with obstructive hydrocephalus who failed an endoscopic third ventriculostomy.
      FINDINGS: Seventy one patients of obstructive hydrocephalus who underwent ETV in
      our institution were included in this study. Aetiology of hydrocephalus included
      congenital aqueductal stenosis in 42 and tubercular meningitis (TBM) in 29
      patients. Failure of ETV was seen in 15 (21%) patients. These 15 patients
      included 6 (14.3%) from the congenital group and 9 (31.0%) patients from the TBM
      group. Iohexol CT ventriculography confirmed a patent stoma (suggesting a complex
      hydrocephalus) in 10 (66.7%) out of the 15 failed ETV cases. The incidence of
      complex hydrocephalus was more common in TBM group (8/29 patients, 27.60%)
      compared to congenital group (2/42 patients, 4.8%). The complex hydrocephalus
      patients with a patent ETV stoma were successfully managed by a lumbar peritoneal
      (LP) shunt. CONCLUSION: Ten out of the 71 patients (14%) with obstructive
      hydrocephalus who underwent an ETV had a complex hydrocephalus, which was the
      major (66.7%) cause for failure of ETV. Improving methods to detect the exact
      type of hydrocephalus pre-operatively could increase success rate of ETV and
      avoid an unnecessary operative procedure (ETV).

PMID- 19604412
TI  - Absence of association between SERPINE2 genetic polymorphisms and chronic
      obstructive pulmonary disease in Han Chinese: a case-control cohort study.
AB  - BACKGROUND: Recent studies have proposed that the serine protease inhibitor E2
      (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary
      disease (COPD) in Caucasians. However, this issue still remained controversial.
      Additional evidences from populations with different environments and/or genetic
      backgrounds, such as East Asian, would be helpful to elucidate the issue.
      METHODS: In this study, five proposed causal SNPs in SERPINE2 were genotyped in
      327 COPD patients and 349 controls, all of which belonged to the Han population
      sampled from Southwest China. The frequency of each SNP was compared both
      individually and in combination between patients and controls. The potential
      relationship between these SNPs and severity of COPD was also investigated.
      RESULTS: Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage
      disequilibrium (r2 = 1), and the minor allele frequencies were 13.0% and 12.9% in
      case and control cohorts, respectively, with no significant difference observed
      (P = 0.96). We also failed to observe any significant correlation between these
      SNPs and COPD severity (P = 0.67). The other two SNPs (rs7579646 and rs840088)
      also presented a similar pattern. Moreover, four major haplotypes were observed
      in our sample but none showed a significant difference between case and control
      groups (P > 0.1). CONCLUSION: Our results failed to obtain the evidence that
      these SNPs in SERPINE2 contributed to the COPD susceptibility in the Han Chinese
      population.

PMID- 19604414
TI  - Retrospective analysis of treatment outcome in 315 patients with oligodendroglial
      brain tumors.
AB  - Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is
      considered to be well tolerated, side effects frequently lead to dose reduction
      or even discontinuation of treatment of oligodendroglial brain tumors. The
      primary objective of the analysis was to retrospectively compare progression-free
      survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side
      effects). Patients were retrospectively identified from a database containing our
      patients between 1990 and 2003. For the selected cases, all histopathology
      reports were re-evaluated by a local neuropathologist. Based on the updated
      histology data, patients were included in the study if they had at least one
      histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n =
      61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate
      analysis adjusting for prognostic imbalances favouring the PC group showed a
      minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95%
      confidence interval 0.53-1.25; p = 0.346). Younger age (< 50 y) was a
      statistically significant predictor of longer PFS. Significant advantages in
      terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n
      = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus
      oligoastrocytomas (p = 0.002), and WHO degrees II vs. degrees III (p < 0.001).
      Three risk groups regarding OS were identified. Findings support the hypothesis
      that PC may be as effective as PCV chemotherapy, while avoiding the additional
      risks of vincristine. Younger age, lower tumor grade and histology of an
      oligodendroglioma were identified to be favorable prognostic factors.

PMID- 19604416
TI  - Spontaneous uterine rupture.

PMID- 19604418
TI  - Doing what's best.

PMID- 19604415
TI  - The effect of caffeic acid phenethyl ester on the functions of human monocyte
      derived dendritic cells.
AB  - BACKGROUND: Propolis, an ancient herbal medicine, has been reported the
      beneficial effect both in asthma patients and murine model of asthma, but the
      mechanism was not clearly understood. In this study, the effect of caffeic acid
      phenethyl ester (CAPE), the most extensively studied components in propolis, on
      the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.
      RESULTS: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein
      expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS)
      and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly
      inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs
      stimulated by crude mite extract. In contrast, the upregulation of costimulatory
      molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen
      presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IkappaBalpha
      phosphorylation and NF-kappaB activation but not mitogen-activated protein kinase
      (MAPK) family phosphorylation in human MoDCs. CONCLUSION: These results indicated
      that CAPE inhibited cytokine and chemokine production by MoDCs which might be
      related to the NF-kappaB signaling pathway. This study provided a new insight
      into the mechanism of CAPE in immune response and the rationale for propolis in
      the treatment of asthma and other allergic disorders.

PMID- 19604420
TI  - Ontario care providers' considerations regarding models of maternity care.
AB  - OBJECTIVE: There is currently a crisis in the delivery of maternity care in
      Canada, in part due to the significant decline in the number of professionals who
      provide intrapartum care. This study was undertaken (1) to elicit care providers'
      opinions regarding seven proposed models of maternity care, (2) to explore
      barriers to collaborative interprofessional practice, and (3) to identify factors
      that would encourage the practice of intrapartum care. METHODS: A survey seeking
      opinions about models of care, perceived barriers to interprofessional
      collaboration, and factors that might encourage practising intrapartum care was
      mailed to all registered midwives (N = 322) and obstetricians (N = 647) in
      Ontario and to a stratified random sample of family physicians (N = 750) in
      Ontario. RESULTS: Completed questionnaires were received from 80% of midwives,
      64% of obstetricians, and 66% of family physicians. Midwives and obstetricians
      endorsed uniprofessional models and indicated an interest in multiprofessional
      practice. Family physicians were reluctant to choose any models that would have
      them practising intrapartum care. However, family physicians currently providing
      intrapartum care would consider the uniprofessional model in which they delivered
      the babies of the women they were caring for unless they were signed out.
      Midwives identified different philosophies of care as the main barrier to
      collaborative interprofessional maternity care (60.7%); obstetricians and family
      doctors identified liability and insurance issues (60.3% and 38.7%,
      respectively). An adequate on-call arrangement was the key factor potentially
      encouraging midwives and obstetricians to provide intrapartum care (70.3% and
      70.0%, respectively). For family physicians, good medical and obstetrical back-up
      was the first priority (70.8%), followed by on-call arrangements. CONCLUSION: A
      variety of models for providing intrapartum care must be available, as no single
      model meets the needs of all maternity providers. Attention must be given to
      eliminating barriers to collaborative interprofessional practice, coupled with
      enhancing factors that facilitate the delivery of intrapartum care.

PMID- 19604421
TI  - Rates of rubella immunity among immigrant and non-immigrant pregnant women.
AB  - OBJECTIVE: Elimination of congenital rubella syndrome depends not only on
      effective childhood immunization but also on the identification and immunization
      of susceptible women of childbearing age. Since many countries do not immunize
      against rubella, it is possible that some immigrant women may not be immune.
      Moreover, contemporary estimates of rubella immunity among Canadian-born mothers
      are lacking. Accordingly, we sought to compare the immunity status in pregnancy
      of a large number of immigrant and Canadian-born women in Toronto. METHODS: We
      examined data among 5783 consecutive pregnant women who gave birth at an inner
      city hospital in downtown Toronto between 2002 and 2007. Antenatal maternal
      rubella immunity status was recorded at the time of delivery, and assessed
      according to the mother's birthplace. Odds ratios (OR) for rubella immunity were
      adjusted for maternal age, gravidity and duration of residency in Canada.
      RESULTS: Relative to a rate of 93.2% among Canadian-born mothers, the adjusted
      risk of being rubella immune was lowest among women from Northern Africa and the
      Middle East (OR 0.54, 95% CI 0.31-0.94) and China and the South Pacific (OR 0.78,
      95% CI 0.59-1.03). CONCLUSION: Rates of rubella immunity are lower than desired
      among Canadian-born and, especially, new immigrant pregnant women. Under
      immunized populations might be identified at the time of the immigration medical
      examination, while consideration should be given to screening for rubella
      immunity among all young Canadian women before puberty.

PMID- 19604422
TI  - Diagnosing chromosomal abnormalities from "big" to "small" with molecular
      cytogenetic technology.
AB  - We reviewed the available molecular cytogenetic techniques and their potential
      use in prenatal diagnosis of fetuses with multiple congenital anomalies and a
      "normal" standard chromosomal karyotype. We searched Medline to identify reports
      published after 1995 that were related to molecular prenatal diagnosis. After
      review, we reached the following conclusions: 1. In fetuses with a normal
      standard karyotype result, common chromosomal microdeletion syndromes may be
      suspected based on the pattern of congenital anomalies seen on prenatal
      ultrasound. 2. When a microdeletion syndrome is suspected based on the pattern of
      fetal anomalies, FISH testing for the specific molecular locus should be
      undertaken. 3. Routine chromosome analysis, which has been the gold standard for
      prenatal cytogenetic diagnosis, may in the future be replaced by microarray
      technology with increased diagnostic capability for smaller, submicroscopic
      genetic alterations associated with postnatal morbidity. 4. Microarray technology
      has been shown to increase our ability to make a diagnosis of known or new
      chromosomal deletion syndromes in pediatric populations with developmental delay.
      The use of this technology for prenatal diagnosis is currently limited but is
      likely to expand.

PMID- 19604423
TI  - Recent changes in maternal characteristics by socioeconomic status.
AB  - OBJECTIVE: To describe changes in maternal characteristics by socioeconomic
      status, in order to provide a context for recent changes in the frequency of
      obstetric procedures and outcomes, and information for health planning purposes.
      METHODS: All NS residents who delivered between 1988 and 2007 were included in
      the study. Information on maternal characteristics was obtained from the Nova
      Scotia Atlee Perinatal Database, and socioeconomic status information was
      obtained through a confidential link with federal income tax T1 Family Files
      (1988 to 2003). RESULTS: Total births to women < 20 years of age were high (31.5%
      in 2003) and increased in the lowest family income group between 1988 and 2003,
      while rates were low (0.7% in 2003) and decreased in the highest family income
      group. Total births to women >/= 35 years increased by 136% (95% CI 122, 150)
      between 1988-89 and 2006-07. Births to women with a weight >/= 90 kg also
      increased, while those to smokers decreased in all socioeconomic groups. The
      proportion of births to multiparous women with a previous low birth weight infant
      did not change (-5 %, 95% CI -14, 6), although births to women with a previous
      perinatal death declined by 52% (95% CI -60,-42). CONCLUSION: Large secular
      changes have occurred in maternal characteristics over the past two decades, and
      the magnitude of these changes has differed by socioeconomic status.

PMID- 19604424
TI  - Prevalence of urinary incontinence in women with osteoporosis.
AB  - OBJECTIVE: To investigate the prevalence and frequency of urinary incontinence in
      women presenting to a specialist osteoporosis clinic. METHODS: Participants
      included 412 female patients aged 22 to 94 years (mean 62 years) presenting to a
      hospital-based specialist multidisciplinary osteoporosis clinic over one year.
      The presence or absence of urinary incontinence, urgency without leakage, type of
      symptoms (stress, urge, mixed) and frequency of urinary incontinence were
      recorded. RESULTS: Sixty-seven percent of patients (277/412) reported some
      symptoms of urinary incontinence, 23% reported no symptoms and 10% reported
      urgency without any leakage. Of those who reported some urinary incontinence, 51%
      reported symptoms of stress incontinence, urgency, and urge incontinence. Almost
      40% of all patients (163/412) and 59% of those with any urinary incontinence
      (163/277) reported leakage at least once per week. CONCLUSION: The prevalence of
      at least weekly urinary incontinence in this population is much higher than that
      reported in studies of other older adult female populations. There is also a high
      prevalence of incontinence accompanied by urgency in women with osteoporosis.
      Based on these results and because urinary incontinence can limit a woman's
      ability to be physically active and increase the risk of falls and fractures,
      screening for incontinence should be a routine part of osteoporosis management.
      Clinicians seeing patients for osteoporosis should consider the presence of
      incontinence when prescribing exercise for bone health and fall prevention.

PMID- 19604425
TI  - Risk of malignancy index in the evaluation of patients with adnexal masses.
AB  - OBJECTIVE: To determine if the risk of malignancy index (RMI) can distinguish
      between benign and malignant adnexal masses in a population of women referred to
      a department of gynaecologic oncology for surgical resection of an adnexal mass.
      METHODS: We performed a retrospective review of the medical of charts of 259
      consecutive patients. Ninety-six charts did not have data available to calculate
      the RMI, leaving a total of 163 for review. Three definitions of RMI were
      compared; each incorporated menopausal status of the patient, ultrasound
      characteristics of the adnexal mass, and serum CA-125 level. RESULTS: Of the
      masses resected, 105 were benign and 58 were malignant. The area under the ROC
      curve for all three definitions of RMI was 0.87. Using a cut-off of 120, the
      first RMI definition (RMI 1) had a sensitivity of 72% and a specificity of 87%;
      the second (RMI 2) had a sensitivity of 76% and a specificity of 81%; and the
      third (RMI 3) had a sensitivity of 74% and a specificity of 84%. These results
      are generally in agreement with published values. CONCLUSION: We have validated
      the use of RMI to predict the risk of malignancy in a Nova Scotia population of
      women with adnexal masses. This will aid in more selective referral of patients
      to specialized oncology centres for cancer surgery, allowing for appropriate
      management of health care resources and optimization of treatment for women with
      gynaecological malignancies.

PMID- 19604426
TI  - Role of dynamic MRI in surgical decision-making for a postpartum woman with a
      prolapsed degenerating uterine leiomyoma.
AB  - BACKGROUND: Surgical decision-making in the case of postpartum complications
      affecting fibroids can be difficult. We present a case that illustrates the
      potential role of MRI in assisting these decisions. CASE: A 28-year-old woman
      with a known uterine leiomyoma presented on postpartum day 10 with abdominal
      pain, fever, and foul-smelling vaginal discharge. Her condition improved after
      antibiotic therapy, but she subsequently returned to hospital with a liquefied
      fibroid filling the vagina and a solid mass palpable above the dilated cervix.
      Pelvic ultrasound did not conclusively identify the vascular supply or myometrial
      involvement of the mass. MRI identified one fundal vascular pedicle and a very
      thin posterior uterine wall. At abdominal myomectomy, the myometrium was found to
      be only minimally involved, and the fundal vascular pedicle was easily cross
      clamped. CONCLUSION: When available, MRI can be used to clarify the location of
      vascular pedicles and the extent of myometrial involvement of uterine fibroids,
      and it can assist in fibroid-related surgical decision-making.

PMID- 19604427
TI  - Rates of spontaneous and therapeutic abortions following use of antidepressants
      in pregnancy: results from a large prospective database.
AB  - OBJECTIVE: The use of antidepressants during pregnancy remains a controversial
      issue, and there is little information on the risk of spontaneous abortions
      following antidepressant exposure in early pregnancy. We sought to examine
      whether use of antidepressants increases the rates of spontaneous abortion (SA)
      and therapeutic abortion (TA) in women exposed in early pregnancy. METHODS: In a
      cohort of women who contacted the Motherisk program during pregnancy, we compared
      two groups of women, one exposed and the other not exposed to antidepressants
      during pregnancy, and calculated the associated rates of SA and TA. RESULTS:
      Among 937 women exposed to antidepressants prior to and during early pregnancy,
      there were 122 SAs (13.0%) including three ectopic pregnancies, and in the
      comparison group there were 75 SAs (8.0%) and no ectopic pregnancies. The
      relative risk was 1.63 (95% CI 1.24-2.14). Three-fold more women reported a TA in
      the exposed group, 26 (2.4%) compared to 8 (0.7%) in the non-exposed group (RR
      3.25; 95% CI 1.48-7.14). A sub-analysis revealed that in both groups, of 338
      women with a prior SA, 58 (17.2%) reported having a SA in the current pregnancy,
      compared with 61/652 (9.4%) with no prior SA (chi square = 12.09, P lt; 0.001).
      In the antidepressant group, the incidence was 20.7%, and in the non-exposed
      group, it was 13.3%. Logistic regression confirmed that only antidepressant
      exposure and prior SA were significantly associated with current SA. CONCLUSION:
      Exposure to antidepressants in the first trimester of pregnancy appears to be
      associated with a small but statistically significant increased risk of SA and
      decision to terminate a pregnancy. The risk for SA is further elevated with a
      history of previous SA. However, any underlying depression must be taken into
      consideration when evaluating these results.

PMID- 19604428
TI  - Postmenopausal reproduction: in whose interests?

PMID- 19604429
TI  - Ultrasound imaging for the rheumatologist. XXI. Role of ultrasound imaging in
      early arthritis.
AB  - Identification of early indicators of diagnosis and prognosis together with tight
      control of disease activity are the current goals of management of early
      arthritis. Several studies in the literature to date suggest that musculoskeletal
      ultrasonography (US) may have a role in this setting. US is a valid and reliable
      tool for the assessment of inflammatory arthritis - either as an ultra-sensitive
      measure of inflammation or joint damage. US is also useful in the differential
      diagnosis of early arthritis, both identifying disease specific findings and
      integrating clinical findings into structured diagnostic algorithms. Grey scale
      and power Doppler US are sensitive disease activity and severity markers,
      identifying subgroups of patients with poorer clinical and radiological outcomes,
      even once clinical remission has been achieved. The present review provides an
      update of the available data and discusses research issues of ultrasound imaging
      in early arthritis.

PMID- 19604430
TI  - The COX-2 inhibitor market withdrawals and prescribing patterns by
      rheumatologists in patients with gastrointestinal and cardiovascular risk.
AB  - OBJECTIVE: To examine effects of the COX-2 inhibitor market withdrawals on NSAID
      utilization among patients at increased risk of gastrointestinal (GI) and
      cardiovascular (CV) toxicities. METHODS: A prospective cohort study was conducted
      using patients enrolled in the Consortium of Rheumatology Researchers of North
      America (CORRONA) Registry. The study population included rheumatoid arthritis
      (RA) and psoriatic arthritis (PsA) patients prescribed NSAIDs by rheumatologists
      from 1/1/2003 to 12/31/2005. Three cohorts were defined based on calendar year.
      The primary outcome assessed whether or not an NSAID gastroprotective strategy
      was prescribed. Secondary outcomes included rates of COX-2 inhibitor utilization
      and gastroprotective co-therapy utilization, stratified by the presence of
      cardiac and GI risk factors. RESULTS: NSAID gastroprotection utilization
      decreased from 65.1% in 2003 to 47.7% (p<0.001) in 2005. COX-2 inhibitor use
      decreased from 55.1% to 29.2% (p<0.001), whereas nonselective NSAIDs (nsNSAIDs)
      use increased from 50.2% to 73.9% (p=<0.01). Among patients with two or more risk
      factors for NSAID related GI bleeding, gastroprotection decreased from 74.4% in
      2003 to 60.9% (p<0.01). For patients with two or more CV risk factors from 2003
      to 2005, COX-2 inhibitor utilization decreased significantly, whereas nsNSAID
      utilization increased significantly. CONCLUSIONS: The COX-2 inhibitor withdrawals
      resulted in a rapid decline in NSAID gastroprotection prescribed by participating
      U.S. rheumatologists despite the availability of other gastroprotective options.
      Channeling toward nsNSAID use was widespread, including among patients at
      increased CV risk. Longer term follow-up is required to determine the clinical
      significance of these changes in NSAID prescribing, particularly for NSAID
      related GI and CV-related toxicities.

PMID- 19604431
TI  - Imaging of sternocostoclavicular joint in spondyloarthropaties and other
      rheumatic conditions.
AB  - OBJECTIVE: To retrospectively evaluate the role of the various imaging techniques
      in the study of the sternocostoclavicular joint, in patients with
      spondyloarthropathies and other rheumatic conditions and to assess potential
      pitfalls in the radiological diagnosis. SUBJECTS AND METHODS: Thirty patients, 11
      male and 19 female, mean age 45 years, with involvement of the
      sternocostoclavicular joint as part of rheumatologic disorders (psoriatic
      arthritis, ankylosing spondylitis, Tietze syndrome, SAPHO syndrome, and
      condensing osteitis of the clavicle) were studied. Conventional radiography, CT,
      MRI and bone scintigraphy were performed. The following imaging findings were
      evaluated: soft tissue swelling, bone sclerosis, cortical bone erosions, joint
      space narrowing, subchondral sclerosis, periosteal new bone formation, synovial
      reaction and intrarticular effusion. All the images were independently reviewed
      by two musculoskeletal radiologists. RESULTS: Conventional radiography
      demonstrated only sclerosis of the clavicula in 8 pts (26%) and the sternum in 3
      pts (10%), cortical bone erosions in 7 pts (23%), joint space narrowing in 6 pts
      (23%) and periosteal bone formation in 2 pts (10%). At the CT examination
      sclerosis of the clavicula and the sternum was observed in 13 pts (44%), cortical
      bone erosions in 22 pts (76%), joint space narrowing in 10 pts (34%), ligament
      ossification in 12 pts (41%), subchondral sclerosis in 9 pts (34%) and periosteal
      bone formation in 10 pts (34%). The MRI was the most sensitive technique in the
      evaluation of the soft tissue swelling in 9 pts (56%), intrarticular effusion in
      13 pts (81%) and synovial reaction in 13 pts (81%). Finally, bone scintigraphy
      showed an increased uptake at the sterno-costoclavicular joint in all patients
      who underwent the examination. CONCLUSION: The radiological evaluation of the
      anterior chest wall in patients with different rheumatic disorders represents a
      problem of difficult diagnostic evaluation both for the anatomic region
      complexity and for the variability of the radiographic findings. The integrated
      use of X-ray, CT, MRI and nuclear medicine is suggested to avoid misdiagnosis.

PMID- 19604432
TI  - The epidemiology of primary systemic vasculitides involving small vessels in
      Crete (southern Greece): a comparison of older versus younger adult patients.
AB  - BACKGROUND: The frequency of primary systemic small vessel vasculitides (PSV)
      varies among different geographic regions and age categories. We studied PSV in
      patients from middle-eastern Crete (Greece), and compared clinical
      characteristics in younger (<65 years) versus older (> or = 65 years) adult
      patients. METHODS: The records of 67 patients (33 younger, 34 older adults)
      diagnosed with PSV during 1995-2003 who were referred to a mixed
      secondary/tertiary care University Hospital in Crete were reviewed. Data on
      clinical manifestations, diagnosis, therapy, and adverse outcomes (end stage
      renal disease, death) during a median follow-up of 6 (range 0-12) years were
      recorded. Multivariate regression analysis was applied to identify independent
      predictors for adverse outcomes. RESULTS: The overall annual incidence of PSV was
      19.5/million (95% confidence interval [CI] 15.7-23.4), 48.9/million (95% CI 33.8
      63.9) in older and 12.4/million (95% CI 7.7-17) in younger adults. Microscopic
      polyangiitis was more prevalent in older patients (65%) and Wegener's
      Granulomatosis in younger patients (52%). Thirty-one percent of older patients
      developed end-stage renal disease as compared to 11% of younger patients
      (p=0.103). Mortality rates were 60% in older patients and 19% in younger patients
      (p=0.001). In multivariate regression analysis age (Beta=0.33 per 1-year,
      p=0.005), serum creatinine (Beta=0.29 per 1-mg/dL, p=0.011), and lung involvement
      (Beta=0.36, p=0.002) at the time of diagnosis were independent predictors for end
      stage renal disease and/or death. CONCLUSION: This study documents increased
      frequency and significant mortality of PSV among older people in Crete, with MPA
      being the most prevalent type. Age, serum creatinine, and lung involvement are
      important predictors for adverse outcome in these patients.

PMID- 19604433
TI  - Anti-tumor necrosis factor therapy in patients with difficult-to-treat lupus
      nephritis: a prospective series of nine patients.
AB  - OBJECTIVE: To clarify the efficacy and safety of anti-TNF-alpha therapy for
      intractable lupus nephritis. METHODS: In nine patients with systemic
      erythematosus who presented with lupus nephritis resistant to steroids and
      immunosuppressants, 200 mg/body of infliximab was drip-infused three times. No
      changes were made to other treatments for three months after the start of anti
      TNF-alpha therapy, and urinary findings, renal function, serum complement, anti
      DNA antibody, SLE activity, and adverse events were examined for six months after
      the start of anti-TNF-alpha therapy. RESULTS: One of the nine patients developed
      pyelonephritis after the first infliximab injection and received no further
      injections. The remaining eight patients received 3 infliximab injections. Of the
      eight patients, urinary protein decreased after anti-TNF-alpha therapy in six
      patients, and the SLEDAI improved in five patients. Urinary findings and/or SLE
      activity improved in six patients. Of the patients whose urinary protein levels
      decreased after anti-TNF-alpha therapy, proteinuria recurred six months after
      anti-TNF-alpha therapy in one patient. After anti-TNF-alpha therapy, proteinuria
      and the SLEDAI improved significantly. With respect to adverse events, therapy
      was discontinued in one patient who developed pyelonephritis, and one patient
      developed decreased blood pressure due to infusion reactions. In one patient in
      whom the steroid dosage was increased due to poor response to anti-TNF-alpha
      therapy, brainstem infarction occurred four months later. In one patient, anti
      DNA antibody levels increased after therapy, but none of the patients had
      decreased serum complement levels or increased SLE activity. CONCLUSION: In
      intractable lupus nephritis, anti-TNF-alpha therapy improved urinary protein
      levels and SLE activity. Although adverse events must be monitored cautiously, it
      may be possible to use anti-TNF-alpha therapy as a third-line treatment.

PMID- 19604434
TI  - A mismatch between self-reported physical work load and the HAQ: early
      identification of rheumatoid arthritis patients at risk for loss of work
      productivity.
AB  - OBJECTIVE: To explore the combination of data on functioning and work load for
      early identification of patients at risk for diminished work productivity in
      rheumatoid arthritis (RA). PATIENTS AND METHODS: In the FIN-RACo trial, 162
      patients with recent onset RA and available for the workforce were treated with
      either a combination of disease-modifying antirheumatic drugs (DMARDs) or a
      single DMARD for 2 years. Otherwise, they received routine care and were followed
      up for 5 years. Data on their individual income and lost work days came from
      official registers. Loss of productivity was computed by the human capital
      approach. Self-reported data on physical work demand (Finnish Institute for
      Occupational Health Questionnaire) at baseline and on functioning (HAQ) at 6
      months were linked according to the International Classification of Functioning,
      Disability and Health. RESULTS: Data on 112 patients were analyzable at 6 months;
      35 (31%) of them had diminished capacity in functions required at paid work. Any
      mismatch between perceived abilities and requirements predicted future (7 through
      60 months) loss of productivity - on average Euro 14,040 (95% confidence interval
      (CI): 9,143-20,511) per year in patients with the mismatch compared to Euro 3,043
      (1,623-5,534) in those without any mismatch - and was associated with RA-related
      permanent work disability (hazard ratio: 11.6; 95%CI: 4.0-33.4). CONCLUSION:
      Linking together self-reported data about functioning and work load helps in
      early identification of the RA patients at risk for loss of working days.

PMID- 19604435
TI  - Calcium pyrophosphate dehydrate crystal deposition in the ligamentum flavum of
      the cervical spine: histopathological and immunohistochemical findings.
AB  - OBJECTIVE: To investigate the histopathological and immunohistochemical
      properties of degenerative changes in the ligamentum flavum of the cervical spine
      with calcium crystal deposition. METHODS: Sections of the calcified ligamentum
      flavum harvested from 26 patients who required cervical decompression were
      examined by scanning electron microscopy (SEM), energy dispersive X-ray
      microanalysis, immunohistochemical staining [for transforming growth factor (TGF)
      Beta, vascular endothelial growth factor (VEGF), Sox9, and Msx2] and terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling
      (TUNEL) method (for cell apoptosis). RESULTS: Energy dispersive x-ray
      microanalysis and SEM confirmed the deposited calcium to be calcium pyrophosphate
      dihydrate (CPPD) crystals. The calcified ligamentum flavum showed disorganisation
      of the elastic fibre bundles together with increased collagen fibrils in the
      matrix. Abundant hypertrophic chondrocytes were noted around the calcified
      lesions, which were strongly immunoreactive to TGF-Beta and VEGF. Staining for
      Sox9 was positive in metaplastic chondrocytes but negative in hypertrophic
      chondrocytes. Both chondrocytes and mesenchymal cells were positive for Msx2.
      TUNEL-positive hypertrophic chondrocytes were significantly more noticeable in
      nodular than diffusely scattered type of CPPD deposition. CONCLUSIONS: Calcium
      crystal deposition in the cervical ligamentum flavum seems to progress with
      reduction in elastic fibres, increase in collagen fibrils in the matrix, and
      migration of metaplastic hypertrophic chondrocytes, whose differentiation is
      controlled by cytokines and transcriptional factors, and potentially regulate
      crystal formation. The presence of abundant TUNEL-positive hypertrophic
      chondrocytes around CPPD deposition suggests that materials from apoptotic cells
      play some role in crystal deposition.

PMID- 19604436
TI  - Relationship between spinal mobility and disease activity, function, quality of
      life and radiology. A cross-sectional Spanish registry of spondyloarthropathies
      (REGISPONSER).
AB  - OBJECTIVE: To determine the relationship between anthropometric measurements and
      disease activity, functional capacity, quality of life and radiology in Spanish
      patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: A cross
      sectional study was made of 842 patients with definite ankylosing spondylitis
      (REGISPONSER). Sociodemographic data, spinal mobility measurements, Bath AS
      disease activity index (BASDAI), nocturnal pain, Bath AS radiology index (BASRI),
      Bath AS functional index (BASFI), the Short-Format 12 (SF-12) and the AS specific
      quality of life (ASQoL) questionnaire were applied. Pearson correlation
      coefficient analysis and regression models were constructed. RESULTS: There was
      moderate correlation between fingertip-to-floor distance and lateral cervical
      rotation with the BASFI (p<0.01). Good correlation was evident between wall
      occiput distance and lateral cervical rotation with the BASRI (p<0.01). Moderate
      correlation was found between chest expansion, the Schober modified test and
      fingertip-to-floor distance with the total BASRI (p<0.01). The anthropometric
      measurement with the lowest correlation value was lateral lumbar flexion.
      Significant association was found between the Schober modified test and BASFI,
      BASDAI and BASRI (R(2) = 0.37; p<0.001); chest expansion and BASFI, BASDAI and
      BASRI (R(2) = 0.25; p<0.001); wall-occiput distance and BASFI, BASRI and ASQoL
      (R(2) = 0.44; p<0.001); fingertip-to-floor distance and BASFI and BASRI (R(2) =
      0.30; p<0.001); and lateral cervical rotation and BASFI and BASRI (R(2) = 0.34;
      p<0.001). CONCLUSION: In our study, wall-occiput distance and lateral cervical
      rotation showed the strongest correlation to BASRI. Similarly, fingertip-to-floor
      distance and lateral cervical rotation exhibited the closest correlation to
      BASFI.

PMID- 19604437
TI  - Increased lipid levels but unchanged atherogenic index in rheumatoid arthritis
      patients treated with biologic disease modifying antirheumatic drugs: published
      experience.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a major cause of increased mortality
      in rheumatoid arthritis (RA) patients, and it is recommended to treat risk
      factors for CVD in RA patients aggressively, including increased lipid levels.
      However, the effect of biological disease modifying antirheumatic drugs (DMARD)
      on the lipid profile of RA patients remains under-researched, and what data exist
      are often contradictory. OBJECTIVES: To review available data published to date
      on lipid profile changes in RA patients treated with biologic DMARDs. METHODS: We
      searched the PubMed database without time limits until January 31, 2008 for
      original clinical trials regarding the effect of biological DMARDs on the lipid
      profiles of RA patients, tabulating total cholesterol, LDL, HDL and atherogenic
      index (ratio of total cholesterol to HDL) data for RA patients treated with
      biologic DMARDs. Percent change values from baseline to end of study were
      calculated. RESULTS: Eighteen studies fulfilled our inclusion criteria. The total
      cholesterol levels of patients treated with biological DMARDs was reported to
      increase in eleven studies (mean change 14.8%). One study reported a decrease
      (change 4.07%), and six reported no significant change. In HDL levels, nine
      studies reported increases (mean change 13.1%), two reported decreases (mean
      change 8.69%) and six reported no significant changes. Five studies reported an
      increase in LDL levels (mean change 11.2%), no studies reported a decrease, and
      six studies reported no significant change. The atherogenic index was reported to
      increase in two studies (mean change 4.27%), decrease in two studies (mean change
      7.26%), and not significantly change in nine studies. Only a third of the
      reviewed articles reported on the LDL/HDL ratio, but of those that did, two
      reported an increase (mean change 4.55%), one reported a decrease (change 8.03%),
      and three reported no significant changes. DISCUSSION: Our data suggest increases
      in lipid levels between baseline and end of study in clinical trials of RA
      patients treated with biologic DMARDs. However, the clinical implications of this
      finding with regard to cardiovascular outcomes are not clear in part due to the
      fact that in most of the studies the atherogenic index was not significantly
      changed from baseline to end of study. Those studies that do provide data on
      effects on cholesterol rarely provide information on the complete lipid profile.

PMID- 19604438
TI  - Short-term effect of anti-TNF-alpha therapy on nitric oxide production in
      patients with severe rheumatoid arthritis.
AB  - OBJECTIVE: TNF-alpha increases expression of inducible nitric oxide synthase
      (iNOS) in macrophages and vascular endothelial cells. Under normal conditions,
      iNOS activity is very low. However, iNOS activity is stimulated during
      inflammation by cytokines such as TNF-alpha and the amount of NO produced by iNOS
      may be a 1,000-fold greater than that produced by endothelial NOS. Since
      functional iNOS gene polymorphisms have been associated with susceptibility to
      rheumatoid arthritis (RA), drugs blocking TNF-alpha might decrease production of
      cytotoxic concentrations of NO leading to beneficial effect on RA or its
      complications. In the present study we investigated whether the infusion of the
      anti-TNF-alpha-infliximab may yield a short-term effect altering circulating NO
      oxidation products in patients with severe RA. METHODS: We investigated 33 RA
      patients on periodical treatment with infliximab. Serum levels of nitrates,
      nitrites and NOx (nitrites+nitrates) were determined immediately prior to and
      after infliximab infusion. Correlation with clinical variables, laboratory
      markers of inflammation, metabolic syndrome features, adipokines and adhesion
      molecules was also assessed. RESULTS: Upon infliximab administration, serum NOx
      concentrations (microM) decreased significantly ([mean+/-SD: 15.0+/-8.8; median:
      11.9; interquartile range: 9.2-18.5] before infliximab-time 0 (baseline) and
      [12.9+/-6.3; 10.9; 7.8-17.2] after infliximab infusion-time 120 minutes; p=0.03).
      It was also the case for nitrates (9.8+/- 8.3; 7.6; 5.5-10.2] before infliximab
      and [7.5+/-4.0; 6.6; 5.2-10.0] after infliximab infusion; p=0.008). There was a
      positive correlation between basal levels of nitrites and leptin concentration
      prior to infliximab administration. However, no significant correlations between
      NO oxidation products and clinical or other laboratory variables were found.
      CONCLUSIONS: Our results show, for the first time, a short-term effect of anti
      TNF-alpha therapy on the levels of nitric oxide production.

PMID- 19604439
TI  - The use of computer touch-screen technology for the collection of patient
      reported outcome data in rheumatoid arthritis: comparison with standardized paper
      questionnaires.
AB  - OBJECTIVES: To investigate the acceptability, feasibility, reliability and score
      agreement of collecting rheumatoid arthritis (RA) patient-reported outcome (PRO)
      data using an interactive touch-screen computer system. METHODS: Eighty-seven RA
      patients completed both the touch-screen and conventional paper-administered set
      of questionnaires. For this purpose, we have developed a computerized touch
      screen system, namely RHEUMATISM (RHEUMA Touch-screen Italian SysteM), to capture
      PRO data. Variables recorded include the following information: demographic data,
      VAS scores for pain, patient's and physician's assessment of global activity, and
      physician's assessment of general health status, 28-joint counts measuring tender
      and swollen joint, patient self-reported tender joint count, Recent-Onset
      Arthritis Disability index, and laboratory findings. In a further test-retest
      study, 35 patients were evaluated. RESULTS: Although over half the patients had
      no prior computer experience, nearly all found the touch-screen easy to use.
      Moreover, 86% of the patients preferred the computer format to the paper format
      (2%) and 12% of subjects had no preference. The quality of the data collected
      with the touch-screen system was good, with no missed responses. Agreement
      between scores obtained with the two modes of administration was very good, with
      concordance correlation coefficients (CCCs) from 0.887 to 0.972. CCCs were
      similar in men and in women, in subjects with or without prior computer
      experience and in subjects below or above age 65. The electronic questionnaire
      had good test-retest reliability (CCCs from 0.836 to 0.907). CONCLUSIONS:
      Computer touch-screen questionnaires were well accepted by RA patients, with good
      data quality, reliability and score agreement.

PMID- 19604440
TI  - Evaluation of an existing screening tool for psoriatic arthritis in people with
      psoriasis and the development of a new instrument: the Psoriasis Epidemiology
      Screening Tool (PEST) questionnaire.
AB  - OBJECTIVE: To evaluate an existing tool (the Swedish modification of the
      Psoriasis Assessment Questionnaire) and to develop a new instrument to screen for
      psoriatic arthritis in people with psoriasis. DESIGN: The starting point was a
      community-based survey of people with psoriasis using questionnaires developed
      from the literature. Selected respondents were examined and additional known
      cases of psoriatic arthritis were included in the analysis. The new instrument
      was developed using univariate statistics and a logistic regression model,
      comparing people with and without psoriatic arthritis. The instruments were
      compared using receiver operating curve (ROC) curve analysis. RESULTS: 168
      questionnaires were returned (response rate 27%) and 93 people attended for
      examination (55% of questionnaire respondents). Of these 93, twelve were newly
      diagnosed with psoriatic arthritis during this study. These 12 were supplemented
      by 21 people with known psoriatic arthritis. Just 5 questions were found to be
      significant predictors of psoriatic arthritis in this population. Figures for
      sensitivity and specificity were 0.92 and 0.78 respectively, an improvement on
      the Alenius tool (sensitivity and specificity, 0.63 and 0.72 respectively).
      CONCLUSIONS: A new screening tool for identifying people with psoriatic arthritis
      has been developed. Five simple questions demonstrated good sensitivity and
      specificity in this population but further validation is required.

PMID- 19604441
TI  - Chronic arthritis directly induces quantitative and qualitative bone disturbances
      leading to compromised biomechanical properties.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of
      fragility fractures. In RA patients, the direct effect of inflammation on bone is
      difficult to study because their skeleton is also affected by medication with
      corticosteroids and other drugs as well as aging and menopause, which contribute
      to bone fragility. This study used an animal model of chronic arthritis to
      evaluate the direct impact of chronic inflammation on biomechanical properties
      and structure of bone. METHODS: In the SKG mouse chronic arthritis model three
      point bending tests were performed on femoral bones and compression tests on
      vertebral bodies. Collagen structure was analysed using second-harmonic
      generation (SHG) imaging with a two-photon microscope, ultramorphology by
      scanning electron microscopy (SEM) coupled with energy dispersive x-ray
      spectroscopy (EDS) and bone density using water pycnometer. RESULTS: Arthritic
      bones had poor biomechanical quality compared to control bones. SHG, SEM and
      pycnometry disclosed variable signs of impaired collagen organization, poor
      trabecular architecture and low bone density. CONCLUSION: Present data
      demonstrate for the first time that chronic inflammation per se, without
      confounding influence of drugs and aging, leads to impairment of bone
      biomechanics in terms of stiffness, ductility and ultimate strength (fracture).

PMID- 19604442
TI  - Decreased RAGE expression in peripheral blood mononuclear cells of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Interactions between the multiligand receptor for advanced glycation
      end products (RAGE) and its proinflammatory ligands (AGEs, S100/calgranulins,
      HMBG1, Mac-1) may contribute to inflammatory responses playing a key role in the
      pathogenesis of chronic inflammatory diseases such as in rheumatoid arthritis
      (RA). Peripheral blood mononuclear cells (PBMCs) participate in the development
      of chronic inflammatory diseases. This study investigated expression of the RAGE
      variants endogenous secretory RAGE (esRAGE), N-truncated RAGE (NtRAGE) and
      complete RAGE (cRAGE: encoding full-length RAGE, esRAGE and NtRAGE) in PBMCs of
      patients with RA in comparison to healthy control subjects (controls) and to
      patients with Crohn's disease (CD) as another chronic inflammatory disease.
      METHODS: The cRAGE, esRAGE and NtRAGE mRNA expression levels of PBMCs from
      controls, RA and CD patients were measured by real-time PCR. The RAGE protein
      expression was determined by Western blot analysis and the esRAGE plasma levels
      by ELISA. RESULTS: PBMCs of RA patients showed significantly decreased mRNA
      expression for cRAGE (46%), esRAGE (54.0%) and NtRAGE (52%) in comparison to
      healthy controls (100%). For CD patients, also a down-regulation but to a lower
      extent was found (cRAGE: 79%; esRAGE: 76%; NtRAGE: 69%). Related to controls, RA
      PBMCs showed a significantly reduced protein expression of full-length RAGE (53%)
      as well as significantly decreased esRAGE plasma concentrations (70%).
      CONCLUSION: The down-regulation of RAGE isoforms in RA PBMCs may contribute to
      reduced intracellular responses mediated by the cell-standing receptor as well as
      to a lowered capability of trapping inflammatory ligands by circulating esRAGE.

PMID- 19604443
TI  - Impact of short-term therapies with biologics on prothrombotic biomarkers in
      rheumatoid arthritis.
AB  - BACKGROUND: Imbalance of haemostasis in patients with rheumatoid arthritis (RA)
      contributes to future risk of cardiovascular diseases (CVD). Prothrombotic
      molecules, e.g. fibrinogen, D-dimer, and tPA are elevated in plasma of RA
      patients, being associated to CVD. There is no imformation about the influence of
      biological drugs, e.g. anti-CD20 and tumor necrosis factor (TNF) antibodies on
      these prothrombotic molecules. OBJECTIVE: To assess whether anti-TNF and anti
      CD20 therapies modify the profiles of cardiovascular risk factors in patients
      with RA. METHODS: The expression of prothrombotic molecules in plasma was
      investigated in 10 RA patients before and after treatment with TNF-alpha
      antibodies and in another 12 RA patients before and after anti-CD20 treatment.
      RESULTS: Both anti-TNF and anti-CD20 infusions gave rise to clear clinical
      improvement. However, only anti-CD20 infusion significantly (p=0.05) reduced
      concentration of fibrinogen (p=0.05), D-dimer (p<0.001), as well as tPA levels
      (p<0.01). In contrast, in TNF antibody treated patients only tPA levels were
      significantly decreased following the treatment (p<0.05). CONCLUSIONS: Infusion
      of CD20 antibodies to the patients with active RA led to a clearly reduced plasma
      levels of predictors of CVD indicating that this treatment, apart from its anti
      inflammatory properties, may reduce the risk for future CVD in RA.

PMID- 19604444
TI  - Absence of GDF5 does not interfere with LPS Toll-like receptor signaling.
AB  - OBJECTIVES: Growth and differentiation factor 5 (GDF5), member of TGFBeta
      superfamily, has been implicated in limb development, and is known to play an
      important role in joint formation. Its absence leads to brachypodism in mice and
      a number of skeletal malformation syndromes in humans. Recently, an association
      was shown between osteo-arthritis and a 5' UTR polymorphism in GDF5 gene. In
      addition, the role of GDF5 may reach beyond the musculoskeletal system. GDF5
      appears present in a lipopolysaccharide (LPS) receptor cluster. Absence of GDF5
      may limit the response to LPS. This may have consequences for immune responses
      and macrophage function in general, and for arthritis in particular. Here we
      compared the sensitivity of Gdf5(Bp-J/Bp-J) mice and wild type (WT) mice to LPS.
      METHODS: Peritoneal macrophages from Gdf5(Bp-J/Bp-J) mice and WT mice were
      stimulated for 18h with LPS (0, 10 or 100 ng/ml). The supernatant was collected
      and TNF release was measured by ELISA and by an indirect luciferase assay using
      LNF-luc C3 cells. Gdf5(Bp-J/Bp-J) mice and WT mice were injected with LPS i.p.
      (30 mg/kg) and LPS induced lethality was checked every 3 hours for 36 hours.
      RESULTS: Gdf5(Bp-J/Bp-J) macrophages showed no difference in TNF expression upon
      LPS stimulation measured by ELISA and by indirect luciferase assay. Gdf5(Bp-J/Bp
      J) mice died upon a lethal dose of LPS, as is seen in WT controls. CONCLUSION:
      Absence of Gdf5 appears not to affect the LPS response. Mice with a reduced
      expression of Gdf5 can be used in disease models which are dependent on LPS
      boost.

PMID- 19604445
TI  - Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no
      association with response to therapy nor with drug-related adverse events in an
      Italian population of rheumatic patients.
AB  - OBJECTIVE: MTHFR is an enzyme involved in the folate pathway. It has been
      suggested that common polymorphisms in its gene (C677T and A1298C) could be
      related to different methotrexate (MTX) response and toxicity in rheumatoid
      arthritis (RA) patients. Agreement has not been found yet and there is no data on
      rheumatic Italian patients. The aim of this study is to determine if a genetic
      screening can help in planning the treatment in these patients. METHODS: We
      enrolled 84 Northern Italian patients affected by RA (n=79), psoriatic arthritis
      (n=4) and ankylosing spondylitis (n=1), who received MTX. Subjects who achieved
      at least ACR20 response in 6 months and maintained it during the following 6
      months were defined as "responders"; those who did not obtain a disease control
      after 6 months of MTX were classified as "non responders". Patients who
      experienced MTX adverse events were defined "with toxicity", those who did not,
      as "without toxicity". Genotypes were determined by polymerase chain reaction.
      RESULTS: Genotype frequency was consistent with that reported in a healthy
      population from Italy. We did not find any statistically significant difference
      in genotype/allele distribution between the groups. In patients receiving folic
      acid supplementation MTX toxicity was recorded only in 18 cases (24%), while all
      the 8 patients not receiving it experienced MTX adverse events (p=0.00).
      CONCLUSION: In our study we did not find any association between MTHFR
      genotype/allele and MTX response or toxicity. At the moment there is not
      sufficient evidence for MTHFR screening in patients who are candidate for MTX.

PMID- 19604446
TI  - Visceral leishmaniasis and anti-TNF-alpha therapy: case report and review of the
      literature.
AB  - OBJECTIVES: Visceral leishmaniasis (VL) is an extremely rare example of
      opportunistic infection in patients treated with TNF-alpha antagonists and only a
      few cases have been described. In this paper risk factors, clinical features,
      diagnostic work-up and outcome of patients developing VL under biologic therapy
      are described. METHODS: Case report and review of the published cases of VL in
      patients under biologic treatment. RESULTS: We retrieved six patients, including
      ours, all of whom presented anarchic fever and pancytopenia. In 5 cases,
      splenomegaly was detected. The same number of patients came from endemic areas
      for VL. In the majority of the cases a bone marrow examination was not
      diagnostic, requiring the performance of a second one and/or the execution of
      other diagnostic tests. One fatal outcome was observed. CONCLUSION: Even if VL
      represents a sporadic complication of biologic treatments, its presence should
      always be suspected in patients developing a triad of signs and symptoms
      constituted by fluctuant fever, pancytopenia and splenomegaly, especially if
      coming from endemic areas. In these cases an extensive diagnostic work-up must be
      warranted. Atypical and confusing features may resemble autoimmune diseases at
      presentation and during the course of the illness.

PMID- 19604447
TI  - Is the clinical picture of Schnitzler syndrome always Schnitzler syndrome?
AB  - Here we present two cases, a female and a male patient with Schnitzler-like
      syndrome. Both patients had two major (monoclonal gammopathy and chronic
      urticaria) and almost all minor symptoms (e.g. arthralgia, bone pain, fever,
      etc.) of Schnitzler syndrome. It is considered that interleukine (IL)-1 has
      important influence on immunopathogenesis of Schnitzler syndrome. However, when
      looked at the immune response in our two patients, we found significant
      differences between them. In the sera of the female patient, IL-1beta was
      increased. However, the highest increase was found for granulocyte- colony
      stimulating factor (G-CSF), IL-32 alpha and IL-17E (IL-25). The male patient had
      a significant increase in the percentage of NK-cells, a decrease in CD4+ helper
      cells and no increase in cytokine levels. In both patients an increase in CD40L
      (CD154) was found. Our statement is that, besides clinical symptoms and signs,
      additional immune parameters should be tested before diagnosis of Schnitzler
      syndrome is established.

PMID- 19604448
TI  - Selective modulation of T-cell co-stimulation: a novel mode of action for the
      treatment of rheumatoid arthritis.
AB  - Disease-modifying antirheumatic drug therapy, including biological treatments
      that act via tumour necrosis factor (TNF)-alpha blockade, have benefited numerous
      patients suffering from rheumatoid arthritis (RA). However, a portion of the
      patient population is unresponsive to initial therapy, experience a decline in
      response over time or may develop side effects to treatment. These factors
      illustrate the requirement for additional therapy options, with novel modes of
      action, in order to treat this chronic and disabling disease. Activated T cells
      predominate in the disease processes of RA. Therefore, one rational approach to
      therapy is to modulate or target T cells. Abatacept is a first-in-class agent
      that targets T-cell modulation via the co-stimulatory CD80/CD86:CD28 pathway.
      Preclinical studies and clinical trials have demonstrated both the rationale and
      efficacy of using T-cell modulation as a therapeutic approach and, as a result,
      abatacept is currently approved in the European Union for the treatment of RA in
      adults with moderately to severely active disease who have not responded to TNF
      alpha antagon-ist therapy. This review will highlight abatacept as an important
      treatment option in the therapeutic repertoire for RA that selectively modulates
      T-cell co-stimulation.

PMID- 19604449
TI  - MHC class I and II expression in juvenile dermatomyositis skeletal muscle.
AB  - OBJECTIVE: To assess MHC I and II expressions in muscle fibres of juvenile
      dermatomyositis (JDM) and compare with the expression in polymyositis (PM),
      dermatomyositis (DM) and dystrophy. PATIENTS AND METHODS: Forty-eight JDM
      patients and 17 controls (8 PM, 5 DM and 4 dystrophy) were studied. The mean age
      at disease onset was 7.1+/-3.0 years and the mean duration of weakness before
      biopsy was 9.4+/-12.9 months. Routinehistochemistry and immunohistochemistry
      (StreptABComplex/HRP) for MHC I and II (Dakopatts) were performed on serial
      frozen muscle sections in all patients. Mann-Whitney, Kruskal Wallis, chi-square
      and Fisher's exact statistical methods were used. RESULTS: MHC I expression was
      positive in 47 (97.9%) JDM cases. This expression was observed independent of
      time of disease, corticotherapy previous to muscle biopsy and to the grading of
      inflammation observed in clinical, laboratorial and histological parameters. The
      expression of MHC I was similar on JDM, PM and DM, and lower in dystrophy. On the
      other hand, MHC II expression was positive in just 28.2% of JDM cases and was
      correlated to histological features as inflammatory infiltrate, increased
      connective tissue and VAS for global degree of abnormality (p<0.05). MHC II
      expression was similar in DM/PM and lower in JDM and dystrophy, and it was based
      on the frequency of positive staining rather than to the degree of the MCH II
      expression. CONCLUSIONS: MHC I expression in muscle fibres is a premature and
      late marker of JDM patient independent to corticotherapy, and MHC II expression
      was lower in JDM than in PM and DM.

PMID- 19604451
TI  - Safe re-initiation of infliximab in a patient with renal tuberculosis.

PMID- 19604450
TI  - Impact of involvement of individual joint groups on subdimensions of functional
      ability scales in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the influence of arthritis in individual joint groups
      on subdimensions of functional ability questionnaires in children with juvenile
      idiopathic arthritis (JIA). METHODS: 206 patients were included who had the
      Childhood Health Assessment Questionnaire (C-HAQ) and the Juvenile Arthritis
      Functionality Scale (JAFS) completed simultaneously by a parent and received a
      detailed joint assessment. In each patient, joint involvement (defined as
      presence of swelling, pain on motion/tenderness and/or restricted motion) was
      classified in 3 topographic patterns: Pattern 1 (hip, knee, ankle, subtalar and
      foot joints); Pattern 2 (wrist and hand joints); Pattern 3 (elbow, shoulder,
      cervical spine and temporomandibular joints). Frequency of reported disability in
      each instrument subdimension was evaluated for each joint pattern, present either
      isolatedly or in mixed form. RESULTS: Among patients with Pattern 1, the JAFS
      revealed the greatest ability to capture and discriminate functional limitation,
      whereas impairment in the C-HAQ was more diluted across several subdimensions.
      Both C-HAQ and JAFS appeared to be less reliable in detecting functional
      impairment in the hand and wrist (Pattern 2) than in other body areas. Overall,
      the JAFS revealed a superior ability to discriminate the relative functional
      impact of impairment in individual joint groups among patients with mixed joint
      patterns. CONCLUSION: In children with JIA, a functional measure focused to
      assess the function of individual joint groups (the JAFS) may detect with greater
      precision the functional impact of arthritis in specific body areas than does a
      standard questionnaire based on the assessment of activities of daily living (the
      C-HAQ).

PMID- 19604452
TI  - Progression from non-erosive to erosive form of hand osteo- arthritis. A report
      of two cases.

PMID- 19604453
TI  - Tear fluid measurement of anti-SS-A and anti-SS-B antibody in anti-SS-A and anti
      SS-B seronegative Sjogren's syndrome patients.

PMID- 19604454
TI  - Serum immunoglobulin D levels by age in a healthy Italian pediatric population.

PMID- 19604455
TI  - Causes of death in pediatric systemic lupus erythematosus.

PMID- 19604456
TI  - Outcome in patients with rheumatoid arthritis switching TNF-alpha antagonists: a
      single center, observational study over an 8-year period.

PMID- 19604457
TI  - Early high-dose lipid-lowering therapy to avoid cardiac events: a systematic
      review and economic evaluation.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of high-dose statins (atorvastatin
      80 mg/day, rosuvastatin 40 mg/day and simvastatin 80 mg/day) versus simvastatin
      40 mg/day in individuals with acute coronary syndrome (ACS). DATA SOURCES: Eleven
      bibliographic databases, including MEDLINE, CINAHL, EMBASE, Cochrane Database of
      Systematic Reviews, CENTRAL, DARE and NHS EED, were searched from inception to
      2008. REVIEW METHODS: Data relating to study design, baseline patient
      characteristics, clinical or surrogate outcome, and adverse events were
      abstracted, and methodological quality was assessed according to standard
      methods. A synthesis of the available evidence was performed using a Bayesian
      mixed treatment meta-analysis using both direct and indirect evidence. An
      existing Markov model was modified to explore the costs and benefits associated
      with a lifetime of the differing treatment regimens. RESULTS: A total of 3345
      titles and abstracts were screened for inclusion in the review of clinical
      effectiveness and 125 full papers retrieved and assessed in detail. Of these, 30
      papers met the inclusion criteria for the review, describing 28 trials. The
      Bayesian mixed treatment meta-analysis demonstrated a clear dose-response
      relationship in terms of reductions in low-density lipoprotein cholesterol (LDL
      c), with rosuvastatin 40 mg/day achieving the greatest percentage reduction (56%)
      from baseline, followed by atorvastatin 80 mg/day (52%), simvastatin 80 mg/day
      (45%) and simvastatin 40 mg/day (37%). Although serious adverse events with
      statins are rare, their incidence is likely to be greater with higher doses.
      Several clinical scenarios were used to explore the effect of adherence on the
      cost-effectiveness of the treatment regimens. Using a threshold of 20,000 pounds
      per quality-adjusted life-year (QALY) and assuming that the benefits and
      adherence rates observed in the clinical trials are generalisable to a clinical
      setting and that individuals who do not tolerate the higher-dose statins are
      prescribed simvastatin 40 mg/day, then simvastatin 80 mg/day, atorvastatin 80
      mg/day and rosuvastatin 40 mg/day would be considered cost-effective compared
      with simvastatin 40 mg/day in individuals with ACS. Simvastatin 80 mg/day is not
      well tolerated because of the high incidence rates of less severe adverse events
      such as myopathy (26-fold higher than rates in those receiving simvastatin 20
      mg/day), which are likely to affect adherence levels in clinical practice. The
      reference case shows that rosuvastatin is the optimal treatment for individuals
      with a recent history of ACS using a threshold of 20,000 pounds per QALY.
      However, this is based on the assumption that the additional incremental
      reductions in LDL-c observed in patients treated with rosuvastatin 40 mg/day
      compared with atorvastatin will transfer into corresponding changes in relative
      risks of cardiovascular events. CONCLUSIONS: Simvastatin 80 mg/day cannot be
      recommended because of the high incidence rates of adverse events. If the cost of
      atorvastatin decreases in line with that observed for simvastatin when the patent
      ends in 2011, atorvastatin 80 mg/day will be the most cost-effective treatment
      for all thresholds; if the cost reduces to 25% of the current value, atorvastatin
      80 mg/day will be the most cost-effective treatment for thresholds between 5000
      pounds and 30,000 pounds per QALY. Large long-term RCTs reporting effects in
      terms of clinical events are required to determine the optimum statin use for
      subgroups.

PMID- 19604458
TI  - Tyrosine kinase inhibitors in systemic sclerosis: the case for imatinib.

PMID- 19604459
TI  - Juvenile dermatomyositis: the role of cytokine gene polymorphisms in conferring
      risk and protection.

PMID- 19604460
TI  - Clinical update on teriparatide.
AB  - Teriparatide (recombinant human parathyroid hormone ) is an anabolic agent
      approved for the treatment of patients at high risk for fracture. The Fracture
      Prevention Trial administered teriparatide to treatment-naive patients, leading
      to its US Food and Drug Administration approval in 2002. Clinical trial data
      using antiresorptive agents administered before, during, and after any
      parathyroid hormone (PTH) therapy, as well as alternative PTH dosing, have
      provided additional insight yet raise fundamental questions about the most
      appropriate use of teriparatide. This article provides an update on teriparatide,
      focusing on its mechanism of action compared with other antiresorptive agents,
      indications, adverse effects, therapy duration, combination therapy,
      contraindications, and cost effectiveness.

PMID- 19604462
TI  - Advances in renal bone disease: osteoporosis and chronic kidney disease.
AB  - Osteoporosis is a common bone disease characterized by low bone density,
      microarchitectural deterioration of bone tissue, and a consequent increase in
      fracture risk. Recent decades have seen major advances in the understanding of
      the pathophysiology, prevention, and treatment of this disorder. Chronic kidney
      disease (CKD) affects more than 20 million Americans and is associated with
      unique metabolic mineral disorders related to low bone density and increased
      fractures. Because many patients with low bone density may have CKD, and the
      combination of osteoporosis and CKD may further increase fracture risk with
      increased morbidity and mortality, appropriate identification is necessary for
      effective management. The clinical, laboratory, and imaging studies currently
      used to diagnose osteoporosis in the general population inadequately detect the
      complex bone and metabolic changes that occur with CKD. This review focuses on
      the pathophysiology of osteoporosis and CKD and discusses problems with current
      diagnostic tools and considerations for treatment regimens.

PMID- 19604461
TI  - Bone health in systemic lupus erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE) confront an increased risk of
      developing osteoporosis and fragility fractures. Traditional risk factors, such
      as smoking, advanced age, physical inactivity, and low weight, are partly
      responsible, but a number of lupus-specific risk factors may also play an
      important role. Chronic, systemic inflammation in patients with SLE has been
      proposed as a possible mechanism for osteoporosis development. Other potential
      risk factors include vitamin D deficiency due to sun avoidance, premature gonadal
      failure, and the chronic use of medications known to increase osteoporosis risk.
      Increased awareness of this potentially preventable condition is warranted, as
      early detection and treatment help optimize bone health and improve long-term
      outcomes in patients with SLE. This article presents recent epidemiologic data
      related to bone health in SLE and discusses preventative and therapeutic
      strategies.

PMID- 19604463
TI  - New insights: elevated follicle-stimulating hormone and bone loss during the
      menopausal transition.
AB  - We hypothesize that a rising follicle-stimulating hormone (FSH) level during the
      menopausal transition, even in the face of a normal estrogen level, contributes
      to increased bone resorption and profound bone loss that is accompanied by
      trabecular perforation and diminished bone strength. FSH has been shown to
      directly stimulate osteoclast formation and bone resorption, and our murine
      genetic studies indicate that the absence of FSH can, in part, protect against
      hypogonadal hyperresorption that causes bone loss. Furthermore, carefully
      conducted human studies, such as the Study of Women Across Nations (SWAN),
      indicate strong correlations between serum FSH levels and bone loss. Potential
      therapeutic implications include the development of antagonists to circulating
      FSH and its osteoclastic receptor.

PMID- 19604466
TI  - The impact and implications of neuropsychiatric systemic lupus erythematosus in
      adolescents.
AB  - Signs and symptoms of neuropsychiatric systemic lupus erythematosus (NPSLE), as
      defined by the American College of Rheumatology case definitions, occur commonly
      in adolescents with lupus. Thought and mood disorders are more difficult to
      identify than specific central or peripheral nervous system injuries.
      Furthermore, thought and mood disorders must be differentiated from other causes,
      including traumatic, metabolic, endocrinologic, toxic, and infectious etiologies.
      It is also important to recognize that primary mood and thought disorders can
      present in adolescence. The effects of chronic disease during adolescent
      development can also trigger alterations in mood and cognitive function. This
      article reviews proposed etiologies of injury, diagnosis, and differential
      diagnosis of NPSLE. At this time, no specific test identifies NPSLE as the cause
      of mood and cognitive changes; however, current efforts to standardize evaluation
      of cognitive function and develop imaging techniques that identify anatomic brain
      changes will improve the practice of rheumatology.

PMID- 19604465
TI  - The use of Doppler ultrasound to evaluate lesions of localized scleroderma.
AB  - Doppler ultrasound shows great promise for the evaluation of localized
      scleroderma (LS). Disease-related structural changes, such as tissue thickening,
      atrophy, and architectural alterations, can be readily detected using ultrasound.
      High spatial resolution enables monitoring of changes in tissue thickness over
      the course of disease and treatment. Doppler ultrasound may also aid assessment
      of disease activity. Both abnormal tissue echogenicity and vascularity levels can
      represent disease activity in some patients. Because tissue thickness,
      echogenicity, and vascularity vary with body site and age, accurate ultrasound
      evaluation of the LS lesion requires comparison to a control site, ideally the
      contralateral side. Evaluation of deeper tissues is important, as disease
      involvement may reside primarily below the dermis. Further study is needed to
      determine the validity, sensitivity, and reliability of ultrasound for LS.

PMID- 19604464
TI  - Denosumab for joints and bones.
AB  - Denosumab is an investigational, fully human monoclonal antibody with a high
      affinity and specificity for receptor activator of nuclear factor kappaB ligand
      (RANKL), a cytokine member of the tumor necrosis factor family. RANKL, an
      essential mediator of osteoclast formation, function, and survival, plays a major
      role in the pathogenesis of postmenopausal osteoporosis, structural damage in
      rheumatoid arthritis, and bone loss associated with other skeletal disorders.
      Denosumab suppresses bone turnover by inhibiting the action of RANKL on
      osteoclasts. Denosumab reduces bone turnover and increases bone mineral density
      in postmenopausal women with low bone mineral density, reduces fracture risk in
      women with postmenopausal osteoporosis, and inhibits structural damage in
      patients with rheumatoid arthritis when added to ongoing methotrexate treatment.
      It is generally well tolerated, with a good safety profile. Adverse and serious
      adverse events, including infections and malignancy, are similar in patients
      treated with denosumab or placebo.

PMID- 19604467
TI  - Biomarkers for renal disease in childhood.
AB  - A kidney biopsy is currently required to diagnose lupus nephritis (LN).
      Invasiveness related to kidney biopsies, however, makes it a prohibitive approach
      in daily clinical practice for the assessment of LN-related activity and damage.
      The lack of accurate LN biomarkers inhibits effective testing of new, less toxic
      medications. Research in LN biomarkers involves two principal methods: 1) the
      candidate biomarker approach that tests molecules known to be involved in LN
      pathogenesis, and 2) broad-based biomarker-screening techniques. These methods
      suggest that the following may all be potent LN biomarkers: CCL2 (chemokine
      ligand 2; also known as MCP-1 ); CCL5 (chemokine ligand 5; also known as RANTES
      ); and CX3CL1 (chemokine ligand 1; also known as fractalkine); IP-10 (interferon
      inducible protein 10; also known as chemokine ligand 10); neutrophil gelatinase
      associate lipocalin; hepcidin; adiponectin; transferrin; ceruloplasmin; lipocalin
      like prostaglandin synthetase-D; and orosomucoid.

PMID- 19604468
TI  - Ocular complications of childhood rheumatic diseases: nonuveitic inflammatory eye
      diseases.
AB  - Ocular involvement is common in pediatric rheumatologic diseases, supporting the
      concept that these conditions do not manifest in isolation but are components of
      a multisystem inflammatory process. It remains unclear why the eye and its
      adjacent tissues become a target during paninflammatory disease. Pediatric
      rheumatologists must recognize ocular disorders, as these conditions
      significantly concern the treatment team managing serious cases of inflammatory
      eye disease. Close collaboration between the treating rheumatologist and
      ophthalmologist is required to prevent potentially devastating outcomes.
      Therapeutic interventions, such as topical steroids, systemic immunosuppressants,
      and biologics, must balance the necessity of controlling ocular inflammation and
      treatment-related adverse effects. This article-the second in a series on ocular
      complications of childhood rheumatic diseases-reviews the presentation and
      management of the more common nonuveitic inflammatory ocular manifestations of
      childhood rheumatologic disease.

PMID- 19604469
TI  - Oxygenases get to grips with polypeptides.

PMID- 19604470
TI  - KasA, another brick in the mycobacterial cell wall.

PMID- 19604471
TI  - (G2)BRinging an E2 to E3.

PMID- 19604473
TI  - Interpreting a low resolution map of human U1 snRNP using anomalous scatterers.
AB  - We recently determined the crystal structure of the functional core of human U1
      snRNP, consisting of nine proteins and one RNA, based on a 5.5 A resolution
      electron density map. At 5-7 A resolution, alpha helices and beta sheets appear
      as rods and slabs, respectively, hence it is not possible to determine protein
      fold de novo. Using inverse beam geometry, accurate anomalous signals were
      obtained from weakly diffracting and radiation sensitive P1 crystals. We were
      able to locate anomalous scatterers with positional errors below 2 A. This
      enabled us not only to place protein domains of known structure accurately into
      the map but also to trace an extended polypeptide chain, of previously
      undetermined structure, using selenomethionine derivatives of single methionine
      mutants spaced along the sequence. This method of Se-Met scanning, in combination
      with structure prediction, is a powerful tool for building a protein of unknown
      fold into a low resolution electron density map.

PMID- 19604472
TI  - Improving structure-based function prediction using molecular dynamics.
AB  - The number of molecules with solved three-dimensional structure but unknown
      function is increasing rapidly. Particularly problematic are novel folds with
      little detectable similarity to molecules of known function. Experimental assays
      can determine the functions of such molecules, but are time-consuming and
      expensive. Computational approaches can identify potential functional sites;
      however, these approaches generally rely on single static structures and do not
      use information about dynamics. In fact, structural dynamics can enhance function
      prediction: we coupled molecular dynamics simulations with structure-based
      function prediction algorithms that identify Ca(2+) binding sites. When applied
      to 11 challenging proteins, both methods showed substantial improvement in
      performance, revealing 22 more sites in one case and 12 more in the other, with a
      modest increase in apparent false positives. Thus, we show that treating
      molecules as dynamic entities improves the performance of structure-based
      function prediction methods.

PMID- 19604474
TI  - Structure and function of an ADP-ribose-dependent transcriptional regulator of
      NAD metabolism.
AB  - Besides its function as an essential redox cofactor, nicotinamide adenine
      dinucleotide (NAD) also serves as a consumable substrate for several reactions
      with broad impact on many cellular processes. NAD homeostasis appears to be
      tightly controlled, but the mechanism of its regulation is little understood.
      Here we demonstrate that a previously predicted bacterial transcriptional
      regulator, NrtR, represses the transcription of NAD biosynthetic genes in vitro.
      The NAD metabolite ADP-ribose functions as an activator suppressing NrtR
      repressor activity. The presence of high ADP-ribose levels in the cell is
      indicative of active NAD turnover in bacteria, which could signal the activation
      of NAD biosynthetic gene expression via inhibiting the repressor function of
      NrtR. By comparing the crystal structures of NrtR in complex with DNA and with
      ADP-ribose, we identified a "Nudix switch" element that likely plays a critical
      role in the allosteric regulation of DNA binding and repressor function of NrtR.

PMID- 19604475
TI  - Mg2+-assisted catalysis by B. stearothermophilus TrpRS is promoted by allosteric
      effects.
AB  - Mn(2+)-assisted catalysis by B. stearothermophilus TrpRS parallels that in
      polymerases and reduces specificity in amino acid activation. As predicted by
      nonequilibrium molecular dynamics simulations, multivariant thermodynamic cycles
      with [ATP]-dependent Michaelis-Menten kinetics and Mn(2+) for Mg(2+) substitution
      demonstrate energetic coupling of ATP affinities to the metal; to lysines K111
      and K192, which interact via the PPi leaving group; and to K195, which couples
      differently to the metal via the alpha-phosphate. However, net coupling to the
      metal opposes catalysis in both ground (K(M)) and transition (k(cat)) states. The
      10(5)-fold rate acceleration by Mg(2+)-protein interactions therefore requires
      additional favorable protein-metal couplings. Examples include longer-range,
      i.e., allosteric, interactions previously illustrated by the remote F37I
      mutation, which both reduces k(cat) and enhances catalytic assist by Mn(2+),
      relative to that by Mg(2+). These data support a model linking metal-assisted
      phosphoryl transfer catalysis to domain movement, and hence to free-energy
      transduction in a broad range of enzymes.

PMID- 19604476
TI  - Amidation of bioactive peptides: the structure of the lyase domain of the
      amidating enzyme.
AB  - Many neuropeptides and peptide hormones require amidation of their carboxy
      terminal for full biological activity. The enzyme peptidyl-alpha-hydroxyglycine
      alpha-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of
      this reaction, N-dealkylation of the peptidyl-alpha-hydroxyglycine to generate
      the alpha-amidated peptide and glyoxylate. Here we report the X-ray crystal
      structure of the PAL catalytic core (PALcc) alone and in complex with the
      nonpeptidic substrate alpha-hydroxyhippuric acid. The structures show that PAL
      folds as a six-bladed beta-propeller. The active site is formed by a Zn(II) ion
      coordinated by three histidine residues; the substrate binds to this site with
      its alpha-hydroxyl group coordinated to the Zn(II) ion. The structures also
      reveal a tyrosine residue (Tyr(654)) at the active site as the catalytic base for
      hydroxyl deprotonation, an unusual role for tyrosine. A reaction mechanism is
      proposed based on this structural data and validated by biochemical analysis of
      site-directed PALcc mutants.

PMID- 19604477
TI  - Replication across template T/U by human DNA polymerase-iota.
AB  - Human DNA polymerase-iota (Poliota) incorporates correct nucleotides opposite
      template purines with a much higher efficiency and fidelity than opposite
      template pyrimidines. In fact, the fidelity opposite template T is so poor that
      Poliota inserts an incorrect dGTP approximately 10 times better than it inserts
      the correct dATP. We determine here how a template T/U is accommodated in the
      Poliota active site and why a G is incorporated more efficiently than an A. We
      show that in the absence of incoming dATP or dGTP (binary complex), template T/U
      exists in both syn and anti conformations, but in the presence of dATP or dGTP
      (ternary complexes), template T/U is predominantly in the anti conformation. We
      also show that dATP and dGTP insert differently opposite template T/U, and that
      the basis of selection of dGTP over dATP is a hydrogen bond between the N2 amino
      group of dGTP and Gln59 of Poliota.

PMID- 19604478
TI  - Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing
      prolyl hydroxylases.
AB  - The oxygen-dependent hydroxylation of proline residues in the alpha subunit of
      hypoxia-inducible transcription factor (HIFalpha) is central to the hypoxic
      response in animals. Prolyl hydroxylation of HIFalpha increases its binding to
      the von Hippel-Lindau protein (pVHL), so signaling for degradation via the
      ubiquitin-proteasome system. The HIF prolyl hydroxylases (PHDs, prolyl
      hydroxylase domain enzymes) are related to the collagen prolyl hydroxylases, but
      form unusually stable complexes with their Fe(II) cofactor and 2-oxoglutarate
      cosubstrate. We report crystal structures of the catalytic domain of PHD2, the
      most important of the human PHDs, in complex with the C-terminal oxygen-dependent
      degradation domain of HIF-1alpha. Together with biochemical analyses, the results
      reveal that PHD catalysis involves a mobile region that isolates the
      hydroxylation site and stabilizes the PHD2.Fe(II).2OG complex. The results will
      be of use in the design of PHD inhibitors aimed at treating anemia and ischemic
      disease.

PMID- 19604479
TI  - EM-fold: De novo folding of alpha-helical proteins guided by intermediate
      resolution electron microscopy density maps.
AB  - In medium-resolution (7-10 A) cryo-electron microscopy (cryo-EM) density maps,
      alpha helices can be identified as density rods whereas beta-strand or loop
      regions are not as easily discerned. We are proposing a computational protein
      structure prediction algorithm "EM-Fold" that resolves the density rod
      connectivity ambiguity by placing predicted alpha helices into the density rods
      and adding missing backbone coordinates in loop regions. In a benchmark of 11
      mainly alpha-helical proteins of known structure a native-like model is
      identified in eight cases (rmsd 3.9-7.9 A). The three failures can be attributed
      to inaccuracies in the secondary structure prediction step that precedes EM-Fold.
      EM-Fold has been applied to the approximately 6 A resolution cryo-EM density map
      of protein IIIa from human adenovirus. We report the first topological model for
      the alpha-helical 400 residue N-terminal region of protein IIIa. EM-Fold also has
      the potential to interpret medium-resolution density maps in X-ray
      crystallography.

PMID- 19604480
TI  - Crystal structures of Mycobacterium tuberculosis KasA show mode of action within
      cell wall biosynthesis and its inhibition by thiolactomycin.
AB  - Mycobacteria have a unique cell wall consisting of mycolic acids, very-long-chain
      lipids that provide protection and allow the bacteria to persist within human
      macrophages. Inhibition of cell wall biosynthesis is fatal for the organism and a
      starting point for the discovery and development of novel antibiotics. We
      determined the crystal structures of KasA, a key enzyme involved in the
      biosynthesis of long-chain fatty acids, in its apo-form and bound to the natural
      product inhibitor thiolactomycin. Detailed insights into the interaction of the
      inhibitor with KasA and the identification of a polyethylene glycol molecule that
      mimics a fatty acid substrate of approximately 40 carbon atoms length, represent
      the first atomic view of a mycobacterial enzyme involved in the synthesis of long
      chain fatty acids and provide a robust platform for the development of novel
      thiolactomycin analogs with high affinity for KasA.

PMID- 19604481
TI  - Site-directed mutagenesis demonstrates the plasticity of the beta helix:
      implications for the structure of the misfolded prion protein.
AB  - The left-handed parallel beta helix (LbetaH) fold has recently received attention
      as a possible structure for the prion protein (PrP) in its misfolded state. In
      light of this interest, we have developed an experimental system to examine the
      structural requirements of the LbetaH fold, using a known LbetaH protein, UDP-N
      acetylglucosamine acyltransferase (LpxA), from E. coli. We showed that the beta
      helix can tolerate nonhydrophobic residues at interior positions and prolines
      were important, but not critical, in folding of the beta helix. Using our
      structural studies of the LbetaH, we threaded the sequence of the amyloidogenic
      fragment of the prion protein (residues 104-143) onto the structure of LpxA.
      Based on the threading result, we constructed the recombinant PrP-LpxA and tested
      its functional activity in an E. coli antibiotic sensitivity assay. The results
      of these experiments suggest that the amyloidogenic PrP fragment may fold into a
      beta helix in the context of a larger beta-helical structure.

PMID- 19604482
TI  - Formation of the complex between DsbD and PilB N-terminal domains from Neisseria
      meningitidis necessitates an adaptability of nDsbD.
AB  - DsbD transmembrane protein dispatches electrons to periplasmic Trx/DsbE-like
      partners via specific interactions with its N-terminal domain, nDsbD. In the
      present study, PilB N-terminal domain (NterPilB) is shown to efficiently accept
      electrons coming from nDsbD from Neisseria meningitidis. Using an NMR-driven
      docking approach, we have modeled the structure of a mixed disulfide complex
      between NterPilB and nDsbD. We show the needed opening of nDsbD cap-loop whereas
      NterPilB FLHE loop does not seem essential in the formation and stabilization of
      the complex. Relaxation analysis performed on backbone amide groups highlights a
      kind of dynamics transfer from nDsbD cap-loop on NterPilB alpha1 helix,
      suggesting that a mobility contribution is required not only for the formation of
      the mixed disulfide complex, but also for its disruption. Taking into account
      previous X-ray data on covalent complexes involving nDsbD, a cartoon of
      interactions between Trx-like partners and nDsbD is proposed that illustrates the
      adaptability of nDsbD.

PMID- 19604483
TI  - Does Def6 deficiency cause autoimmunity?

PMID- 19604485
TI  - A nonself RNA pattern: tri-p to panhandle.
AB  - In this issue of Immunity, Schlee et al. (2009) defines key RNA structures
      recognized by a cellular viral sensor, RIG-I. This and another recent report by
      Schmidt et al. (2009) provide new insights into the mechanism of antiviral innate
      immunity.

PMID- 19604486
TI  - IL-33 raises alarm.
AB  - The interleukin-1 (IL-1)-like cytokine IL-33 is widely assumed to undergo
      proteolytic maturation by caspase-1. In this issue of Immunity, Luthi et al.
      (2009) show that IL-33 is not a caspase-1 substrate. IL-33 is inactivated by
      caspase-3 and -7 to prevent an inappropriate immune response during apoptosis,
      but not in necrosis.

PMID- 19604487
TI  - Integr-ating IL-1 alpha in antiviral host defenses.
AB  - Adenoviral vectors used in gene therapy induce inflammation, although the
      underlying mechanisms are currently unknown. In this issue of Immunity, Di Paolo
      et al. (2009) implicate interleukin-1 alpha (IL- 1 alpha) in virus-induced
      inflammation and identify the beta 3 integrin as the key receptor regulating IL-1
      alpha activity.

PMID- 19604488
TI  - How to be naive.
AB  - The transcription factor KLF2 directs expression of receptors involved in
      trafficking of naive T cells. In this issue of Immunity, Weinreich et al. (2009)
      demonstrate that KLF2 additionally represses IL-4 production, which otherwise
      induces CXCR3 expression.

PMID- 19604489
TI  - Helping the helpers!
AB  - T follicular helper (Tfh) cells are crucial for generating humoral immune
      responses. In this issue of Immunity, Schmitt et al. (2009) reveal the
      differentiation of human Tfh cells is dependent on dendritic cell-derived
      interleukin-12.

PMID- 19604490
TI  - Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like
      cells in mucosal immunity.
AB  - Blood, lymphoid tissues, and placenta contain diverse subpopulations of natural
      killer (NK) cells that possess distinct immune functions. Recent studies have
      shown that human and mouse gut-associated lymphoid tissues harbor a unique NK
      cell subset that specializes in production of interleukin (IL)-22. This cytokine
      plays a role in host defense of mucosal barriers, although dysregulated secretion
      may cause autoimmune disease. In parallel, human fetal lymphoid tissue inducer
      (LTi) cells and mouse adult LTi-like cells in secondary lymphoid tissues were
      found to release IL-22, as well as IL-17, a proinflammatory cytokine that
      mediates host defense against extracellular pathogens. Here, we compare these
      recently identified immune cells, reviewing what is known about their anatomical
      location, differentiation requirements, function, and potential involvement in
      host defense and autoimmunity. Finally, we discuss the challenges faced in
      furthering our understanding of the developmental relationships and role of NK
      and LTi-like cells in mucosal immune responses.

PMID- 19604491
TI  - Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis
      for MHC-independent missing self recognition.
AB  - The cytolytic activity of natural killer (NK) cells is regulated by inhibitory
      receptors that detect the absence of self molecules on target cells. Structural
      studies of missing self recognition have focused on NK receptors that bind MHC.
      However, NK cells also possess inhibitory receptors specific for non-MHC ligands,
      notably cadherins, which are downregulated in metastatic tumors. We determined
      the structure of killer cell lectin-like receptor G1 (KLRG1) in complex with E
      cadherin. KLRG1 mediates missing self recognition by binding to a highly
      conserved site on classical cadherins, enabling it to monitor expression of
      several cadherins (E-, N-, and R-) on target cells. This site overlaps the site
      responsible for cell-cell adhesion but is distinct from the integrin
      alpha(E)beta(7) binding site. We propose that E-cadherin may coengage KLRG1 and
      alpha(E)beta(7) and that KLRG1 overcomes its exceptionally weak affinity for
      cadherins through multipoint attachment to target cells, resulting in inhibitory
      signaling.

PMID- 19604492
TI  - Opposing effects of TGF-beta and IL-15 cytokines control the number of short
      lived effector CD8+ T cells.
AB  - An effective immune response against infectious agents involves massive expansion
      of CD8(+) T cells. Once the infection is cleared, the majority of these effector
      cells die through unknown mechanisms. How is expansion controlled to maximize
      pathogen clearance and minimize immunopathology? We found, after Listeria
      infection, plasma transforming growth factor beta (TGF-beta) titers increased
      concomitant with the expansion of effector CD8(+) T cells. Blocking TGF-beta
      signaling did not affect effector function of CD8(+) T cells. However, TGF-beta
      controlled effector cell number by lowering Bcl-2 amounts and selectively
      promoting the apoptosis of short-lived effector cells. TGF-beta-mediated
      apoptosis of this effector subpopulation occurred during clonal expansion and
      contraction, whereas interleukin-15 (IL-15) promoted their survival only during
      contraction. We demonstrate that the number of effector CD8(+) T cells is tightly
      controlled by multiple extrinsic signals throughout effector differentiation;
      this plasticity should be exploited during vaccine design and immunotherapy
      against tumors and autoimmune diseases.

PMID- 19604494
TI  - Increased expression of monocarboxylate transporter 1 after acute ischemia of
      isolated, perfused mouse hearts.
AB  - AIMS: Lactate is transported by stereo-specific, pH-dependent monocarboxylate
      transporters (MCTs), of which MCT1 is expressed in abundance in rodent and human
      hearts. This study investigated the expression and functional role of MCT1 in
      mouse hearts during acute myocardial ischemia. MAIN METHODS: Mice hearts were
      isolated and Langendorff-perfused with induced global ischemia (40 min) and
      reperfusion with function and infarct size as end-points. Hearts were collected
      serially for protein extraction and immunoblotting with an MCT1 antibody, and for
      determining subcellular localization with immunogold EM. Immortalized
      cardiomyocytes (HL-1 cells) were injured with hydrogen peroxide, and cell death
      in the presence or absence of the competitive inhibitor of MCT1, d-lactate, was
      evaluated by Trypan blue exclusion. KEY FINDINGS: MCT1 expression increased after
      15 min reperfusion (p<0.05), but was not significantly increased after 60 min.
      MCT1 was localized in mitochondria, plasma membrane, and intercalated disks. At
      15 min reperfusion, gold particle count was increased in the intercalated disks
      (p<0.05). d-lactate administration to isolated hearts either for 5 min before
      ischemia or at the first 5 min of reperfusion increased infarct size (p<0.01). A
      significant impairment of left ventricular performance was found when d-lactate
      was given before ischemia. MCT1 expression was not influenced by d-lactate. When
      HL-1 cells were treated with d-lactate before injury was induced with hydrogen
      peroxide, cell death was increased (p<0.05). SIGNIFICANCE: Inhibition of MCT1
      increases cell death. Increased MCT1 expression after ischemia and reperfusion is
      likely to restore cardiac pH through lactate export.

PMID- 19604493
TI  - Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific
      CD8+ T cell deletion and viral persistence in vivo.
AB  - Although deficient CD8(+) T cell responses have long been associated with chronic
      viral infections, the underlying mechanisms are still unclear. Here we report
      that sustained transforming growth factor-beta (TGF-beta) expression and
      phosphorylation of its signaling mediator, Smad-2, were distinctive features of
      virus-specific CD8(+) T cells during chronic versus acute viral infections in
      vivo. The result was TGF-beta-dependent apoptosis of virus-specific CD8(+) T
      cells that related to upregulation of the proapoptotic protein Bim during chronic
      infection. Moreover, selective attenuation of TGF-beta signaling in T cells
      increased the numbers and multiple functions of antiviral CD8(+) T cells and
      enabled rapid eradication of the persistence-prone virus and memory generation.
      Finally, we found that cell-intrinsic TGF-beta signaling was responsible for
      virus-specific-CD8(+) T cell apoptosis and decreased numbers but was not
      necessary for their functional exhaustion. Our findings reveal persisting TGF
      beta-Smad signaling as a hallmark and key regulator of CD8(+) T cell responses
      during chronic viral infections in vivo.

PMID- 19604495
TI  - Orexin-A acts on the paraventricular nucleus of the midline thalamus to inhibit
      locomotor activity in rats.
AB  - Orexins (hypocretins) are novel peptides that have been shown to play a role in
      control of behavioral arousal. The paraventricular nucleus of the midline
      thalamus (PVT) is one area of the brain that is the most densely innervated by
      orexin fibers. In addition, the PVT sends a dense projection to the nucleus
      accumbens, an area of the striatum involved in the regulation of locomotion. This
      study was done to determine the effect of microinjections of orexin-A (OXA) or
      the orexin receptor antagonist SB334867 in the PVT on locomotor activity (LA) in
      morphine-naive and morphine-sensitized rats. Microinjections of OXA (3 microg/500
      nl) in or near the PVT inhibited LA in rats tested in a novel and familiar
      environment as well as in rats expressing behavioral sensitization to repeated
      injections of morphine. In contrast, microinjections of SB334867 had no effect on
      LA in any of the test situations. Using an approach involving experimenter based
      analysis of ethological behaviors; we found that microinjections of OXA in the
      midline thalamus decreased LA while at the same time increasing the expression of
      grooming and freezing. These results suggest that OXA can act on the PVT and the
      midline thalamus to produce arousal independent of LA.

PMID- 19604496
TI  - D(1)/D(2) receptor-targeting L-stepholidine, an active ingredient of the Chinese
      herb Stephonia, induces non-rapid eye movement sleep in mice.
AB  - L-stepholidine, an active ingredient of the Chinese herb Stephonia, is the first
      compound known to have mixed dopamine D(1) receptor agonist/D(2) antagonist
      properties and to be a potential treatment medication for schizophrenia. In
      schizophrenic patients insomnia is a common symptom and could be partly related
      to the presumed over-activity of the dopaminergic system. To elucidate whether
      stepholidine modulates sleep behaviors, we observed its effects on sleep-wake
      profiles in mice. The results showed that stepholidine administered i.p. at doses
      of 20, 40 or 80 mg/kg significantly shortened the sleep latency to non-rapid eye
      movement (non-REM, NREM) sleep, increased the amount of NREM sleep, and prolonged
      the duration of NREM sleep episodes, with a concomitant reduction in the amount
      of wakefulness. Stepholidine at doses of 40 and 80 mg/kg increased the number of
      state transitions from wakefulness to NREM sleep and subsequently from NREM sleep
      to wakefulness. However, stepholidine had no effect on either the amount of REM
      sleep or electroencephalogram power density of either NREM or REM sleep.
      Immunohistochemistry study showed that stepholidine dose-dependently increased c
      Fos expression in neurons of the ventrolateral preoptic area, a sleep center in
      the anterior hypothalamus, as compared with the vehicle control. These results
      indicate that stepholidine initiates and maintains NREM sleep with activation of
      the sleep center in mice, suggesting its potential application for the treatment
      of insomnia.

PMID- 19604497
TI  - Association study of gender identity disorder and sex hormone-related genes.
AB  - To investigate the biological mechanism of gender identity disorder (GID), five
      candidate sex hormone-related genes, encoding androgen receptor (AR), estrogen
      receptors alpha (ERalpha) and beta (ERbeta), aromatase (CYP19), and progesterone
      receptor (PGR) were analyzed by a case-control association study. Subjects were
      242 transsexuals (74 male-to-female patients (MTF) and 168 female-to-male
      patients (FTM)), and 275 healthy age- and geographical origin-matched controls
      (106 males and 169 females). The distributions of CAG repeat numbers in exon 1 of
      AR, TA repeat numbers in the promoter region of ERalpha, CA repeat numbers in
      intron 5 of ERbeta, TTTA repeat numbers in intron 4 of CYP19, and six
      polymorphisms (rs2008112, rs508653, V660L, H770H, rs572698 and PROGINS) of PGR
      were analyzed. No significant difference in allelic or genotypic distribution of
      any gene examined was found between MTFs and control males or between FTMs and
      control females. The present findings do not provide any evidence that genetic
      variants of sex hormone-related genes confer individual susceptibility to MTF or
      FTM transsexualism.

PMID- 19604498
TI  - Stage-dependent transcriptional changes and characterization of paramyosin of the
      bovine lungworm Dictyocaulus viviparus.
AB  - The bovine lungworm Dictyocaulus viviparus is of major economic importance in
      cattle farming in the temperate zones. The invertebrate protein paramyosin is one
      of the main components of muscle thick filaments but can also exhibit
      immunomodulatory functions. It represents a promising vaccine candidate in
      parasitic helminths. In this study, D. viviparus paramyosin (DvPmy) was
      characterized on the transcriptional as well as genomic level. The identified
      genomic sequence comprises 19 introns compared to only 10 introns in the
      Caenorhabditis elegans orthologue. Quantitative real time PCR transcriptional
      analysis revealed paramyosin transcription throughout the whole parasite's life
      cycle with the highest transcription rate in the agile moving first-stage larvae
      and the lowest in motionless hypobiosis induced third stage larvae. Recombinantly
      expressed DvPmy was found to bind collagen and IgG. Thereby the present study is
      the first showing that nematode paramyosin has the capability for
      immunomodulation and thus may be involved in host immune defence.

PMID- 19604499
TI  - Reducing chronic anxiety by making the threatening event predictable: an
      experimental approach.
AB  - Panic disorder is characterized by both specific, phased fear and generalized,
      chronic anxiety. Standard extinction procedures are efficient in reducing
      specific fear. However, methods based on human conditioning research - that are
      capable of reducing chronic anxiety have not yet been thoroughly investigated.
      This study evaluates a new way of reducing chronic anxiety by signaling aversive
      events (or by making them more predictable). Using an experimental approach with
      healthy participants, specific fear and chronic anxiety were operationalized in a
      within-subjects fear-potentiated startle paradigm by, respectively, conditioning
      to a cue by presenting predictable shocks and conditioning to a context induced
      by unpredictable shocks. The results clearly demonstrate that context
      conditioning is reduced when a discrete cue is added that predicts the onset of
      the aversive event. The data suggest that making unpredictable events, such as
      for example panic attacks, predictable, may reduce the generalized and sustained
      anxiety that often complicates exposure treatment.

PMID- 19604500
TI  - Relationships between personal beliefs and treatment acceptability, and
      preferences for behavioral treatments.
AB  - BACKGROUND: The literature on preferences for behavioral interventions is limited
      in terms of understanding treatment-related factors that underlie treatment
      choice. The objectives of this study were to examine the direct relationships
      between personal beliefs about clinical condition, perception of treatment
      acceptability, and preferences for behavioral interventions for insomnia.
      METHODS: The data set used in this study was obtained from 431 persons with
      insomnia who participated in a partially randomized clinical trial and expressed
      preferences for treatment options. The data were collected at baseline. Logistic
      regression was used to examine the relationships between personal beliefs and
      treatment acceptability, and preferences. The relationships between personal
      beliefs and perception of treatment acceptability were explored with
      correlational analysis. RESULTS: Perception of treatment acceptability was
      associated with preferences. Persons viewing the option as convenient tended to
      choose that option for managing insomnia. Personal beliefs were not related to
      preferences. However, beliefs about sleep promoting behaviors were correlated
      with perceived treatment effectiveness. CONCLUSIONS: Perception of treatment
      acceptability underlies expressed preferences for behavioral interventions.
      Personal beliefs about insomnia are not directly associated with preferences.
      Importance is highlighted for providing information about treatment options and
      exploring perception of each option's acceptability during the process of
      treatment selection.

PMID- 19604501
TI  - Soluble glucomannan isolated from Candida utilis primes blood phagocytes.
AB  - It is well documented that the polysaccharide glucomannan (GM), an abundant
      constituent of the fungal cell wall, in the form of particulate induces strong
      activation of phagocytes, however, the effects of soluble GM are not known.
      Activation of phagocyte anti-microbial mechanisms is a crucial part of the innate
      host defense against invading pathogens. However, under uncontrolled inflammatory
      conditions they contribute to damage of surrounding tissues. Thus, to prevent
      these deleterious effects, the activation of phagocytes is a tightly regulated
      process. Therefore, in this study we analyzed the effect of soluble GM on some
      neutrophil functions such as reactive oxygen species production, degranulation,
      and receptor mobilization at the plasma membrane. Soluble GM at the tested
      concentrations did not stimulate oxidative burst of phagocytes directly but
      significantly potentiated oxidative burst in response to opsonized zymosan
      particles. GM induced significant phosphorylation of p47phox subunit of NADPH
      oxidase on Ser345. This priming effect of GM was accompanied by time and
      concentration dependent degranulation characterized by increased surface
      expression of receptors stored in neutrophil granules (CD10, CD11b, CD14, CD35,
      and CD66b). Degranulation was further confirmed by increase of elastase activity
      in media. Thus, it could be suggested that soluble GM induces priming of
      phagocytes connected with their degranulation, the increase of surface receptor
      expression, and potentiation of oxidative burst response to opsonized particles
      through the activation of NADPH oxidase.

PMID- 19604502
TI  - Fine structure characterization of amylopectins from grain amaranth starch.
AB  - The aim of this study was to determine the fine structure of amylopectin from
      grain amaranth. Amaranthus amylopectin was hydrolyzed with alpha-amylase, and
      single clusters and a group of clusters (domain) were isolated by methanol
      precipitation. The domain and the clusters were treated with phosphorylase a and
      then beta-amylase to remove all external chains, whereby the internal structure
      was obtained. The phi,beta-limit dextrins were analyzed on Sepharose CL 6B. The
      average DP (degree of polymerization) and peak-DP values of fractions of clusters
      were 57 and 82, respectively; the values of the domain were 137 and 309,
      respectively. The unit chain length profiles were analyzed by high-performance
      anion-exchange chromatography with pulsed amperometric detector (HPAEC-PAD). The
      results showed that the domain fraction contained approximately 2.2 clusters, and
      single clusters were composed of approximately 13 chains. The phi,beta-limit
      dextrins of the clusters were further hydrolyzed with alpha-amylase to
      characterize their building block composition. The average DP of the branched
      blocks was approximately 11 and they contained on average approximately 2.5
      chains. Their average chain length, internal chain length, and degree of
      branching were approximately 4.3, 2.8, and 14, respectively. A cluster consisted
      of approximately 6 branched blocks, and the internal chain length between the
      blocks was approximately 6.8.

PMID- 19604503
TI  - 1,4-Dioxane-2,5-dione-type monomers derived from l-ascorbic and d-isoascorbic
      acids. Synthesis and polymerisation.
AB  - l-Ascorbic and d-isoascorbic acids have been used as the starting materials for
      the preparation of (3R,4'S)-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-1,4-dioxane
      2,5-dione (IPTA), (3R and S, 4'S,6R)-3-methyl-6-(2',2'-dimethyl-1',3'-dioxolan-4'
      yl)-1,4-dioxane-2,5-dione (IPTP) and (3R,4'R)-3-(2',2'-dimethyl-1',3'-dioxolan-4'
      yl)-1,4-dioxane-2,5-dione (IPEA), three novel 1,4-dioxane-2,5-dione-type
      monomers. Ring-opening homopolymerisation and copolymerisation of the IPTA
      monomer, derived from l-ascorbic acid, with d,l-lactide have been performed. The
      polymers were characterised by elemental microanalysis, as well as IR and (1)H
      and (13)C NMR spectroscopies. GPC was used to estimate product molecular weights,
      and thermal studies (DSC and TGA) revealed that all the polymers were amorphous,
      being stable up to 250 degrees C under nitrogen.

PMID- 19604504
TI  - Evaluation of ARG protein expression in mature B cell lymphomas compared to non
      neoplastic reactive lymph node.
AB  - The participation of Abl-Related Gene (ARG) is demonstrated in pathogenesis of
      different human malignancies. However there is no conclusive evidence on ARG
      expression level in mature B cell lymphomas. In this study we evaluated ARG
      protein expression in Follicular Lymphoma (FL), Burkitt's Lymphoma (BL) and
      Diffused Large B Cell Lymphoma (DLBCL) in comparison with non-neoplastic lymph
      nodes. Semi-quantitative fluorescent ImmunoHistoChemistry was applied on 14, 7
      and 4 patients with DLBCL, FL and BL respectively, adding to 4 normal and 4
      reactive lymph nodes. The mean ratio of ARG/GAPDH expression was significantly
      different (p<0.00) between lymphomas and control samples, with DLBCL having the
      highest ARG expression amongst all. Over expression of ARG was seen in FL and BL,
      with FL expressing statistically more ARG than BL. Moreover, the ARG/GAPDH
      expression ratio increased from DLBCL stage I towards stage VI, all showing
      significantly more ARG expression than FL and BL (in all cases p<0.00).

PMID- 19604505
TI  - Ligation or cross-linking of CD40 has different effects on AGS gastric cancer
      cells.
AB  - A gastric cancer (GC) cell line, AGS, has high-level expression of CD40, a tumor
      necrosis factor receptor (TNFR) family member. CD40 is present on the surfaces of
      a large variety of cells, including B cells, endothelial cells, dendritic cells
      and some carcinoma cells, and delivers signals regulating diverse cellular
      responses, such as proliferation, differentiation, growth suppression, and cell
      death. In this research, we studied the effects of different forms of CD40
      stimulation on AGS cells by flow cytometry, Western blotting and siRNA
      transfection. We found that different forms of CD40 stimulation, either
      recombinant soluble CD40L (sCD40L, ligation) or agonist anti-CD40 antibody (cross
      linking), induced different effects in AGS gastric cancer cells, proliferation or
      apoptosis. We also showed that VEGF provided a significant contribution to sCD40L
      induced proliferation, while agonist anti-CD40 antibody induced GADD45
      upregulation and promoted apoptosis.

PMID- 19604506
TI  - Automated Arabidopsis plant root cell segmentation based on SVM classification
      and region merging.
AB  - To obtain development information of individual plant cells, it is necessary to
      perform in vivo imaging of the specimen under study, through time-lapse confocal
      microscopy. Automation of cell detection/marking process is important to provide
      research tools in order to ease the search for special events, such as cell
      division. In this paper we discuss an automatic cell detection approach for
      Arabidopsis thaliana based on segmentation, which selects the best cell
      candidates from a starting watershed-based image segmentation and improves the
      result by merging adjacent regions. The selection of individual cells is obtained
      using a support vector machine (SVM) classifier, based on a cell descriptor
      constructed from the shape and edge strength of the cells' contour. In addition
      we proposed a novel cell merging criterion based on edge strength along the line
      that connects adjacent cells' centroids, which is a valuable tool in the
      reduction of cell over-segmentation. The result is largely pruned of badly
      segmented and over-segmented cells, thus facilitating the study of cells. When
      comparing the results after merging with the basic watershed segmentation, we
      obtain 1.5% better coverage (increase in F-measure) and up to 27% better
      precision in correct cell segmentation.

PMID- 19604507
TI  - Occult pneumomediastinum in blunt chest trauma: clinical significance.
AB  - INTRODUCTION: Thoracic injuries are potentially responsible for 25% of all trauma
      deaths. Chest X-ray is commonly used to screen patients with chest injury.
      However, the use of computed tomography (CT) scan for primary screening is
      increasing, particularly for blunt trauma. CT scans are more sensitive than chest
      X-ray in detecting intra-thoracic abnormalities such as pneumothoraces and
      pneumomediastinums. Pneumomediastinum detected by chest X-ray or "overt
      pneumomediastinum", raises the concern of possible aerodigestive tract injuries.
      In contrast, there is scarce information on the clinical significance of
      pneumomediastinum diagnosed by CT scan only or "occult pneumomediastinum".
      Therefore we investigated the clinical consequences of occult pneumomediastinum
      in our blunt trauma population. METHODS: A 2-year retrospective chart review of
      all blunt chest trauma patients with initial chest CT scan admitted to a level I
      trauma centre. Data extracted from the medical records include; demographics,
      occult, overt, or no pneumomediastinum, the presence of intra-thoracic
      aerodigestive tract injuries (trachea, bronchus, and/or esophagus), mechanism and
      severity of injury, endotracheal intubation, chest thoracostomy, operations and
      radiological reports by an attending radiologist. All patients with intra
      thoracic aerodigestive tract injuries from 1994 to 2004 were also investigated.
      RESULTS: Of 897 patients who met the inclusion criteria 839 (93.5%) had no
      pneumomediastinum. Five patients (0.6%) had overt pneumomediastinum and 53
      patients (5.9%) had occult pneumomediastinum. Patients with occult
      pneumomediastinum had significantly higher ISS and AIS chest (p<0.0001) than
      patients with no pneumomediastinum. A chest thoracostomy tube was more common
      (p<0.0001) in patients with occult pneumomediastinum (47.2%) than patients with
      no pneumomediastinum (10.4%), as well as occult pneumothorax. None of the
      patients with occult pneumomediastinum had aerodigestive tract injuries (95%CI 0
      0.06). Follow up CT scan of patients with occult pneumomediastinum showed
      complete resolution in all cases, in average 3 h after the initial exam.
      CONCLUSION: Occult pneumomediastinum occurred in approximately 6% of all trauma
      patients with blunt chest injuries in our institution. Patients who had occult
      pneumomediastinum were more severely injured than those who without. However,
      none of the patients with occult pneumomediastinum had aerodigestive tract
      injuries and follow up chest CT scans demonstrated their complete and spontaneous
      resolution.

PMID- 19604509
TI  - Predictive chromatographic simulations for the optimization of recovery and
      aggregate clearance during the capture of monoclonal antibodies.
AB  - Predictive chromatographic simulations were used to assess whether significant
      aggregate clearance, in addition to high step recovery and limited eluate pool
      volumes, can be achieved during protein A affinity chromatography capture steps.
      Such aggregates of the antibody monomer are commonly found in manufacturing
      processes. A lumped desorption-kinetic limiting model was used to describe the
      elution from the chromatography column, as batch isotherm measurements indicated
      no adsorption under elution conditions. In order to quantify the trade-off
      between step recovery and aggregate clearance, independent experiments were first
      performed to obtain the key kinetic parameters. These parameters were used in
      simulations to predict the behavior of bench-scale protein A column runs and
      identify robust operating windows within which good yields and significant
      aggregate clearance can be achieved. Two examples are described. For antibody A,
      a robust window of operation was identified. In this case, the optimal conditions
      were transferred to pilot-plant scale, and the resulting experimental data were
      shown to be in good agreement with model predictions. For antibody B, it was
      found that conditions resulting in high recovery and good aggregate clearance
      were not robust: at the optimal elution conditions, changes of +/-0.1 units in pH
      or +/-1mS/cm in conductivity affected the results substantially.

PMID- 19604510
TI  - Optimization of a heart-cutting multidimensional gas chromatography-based method
      for the assessment of enantiomeric fractions of o,p'-DDT in environmental
      samples.
AB  - The enantiomeric fractions present in soil samples may provide information useful
      in distinguishing recent inputs of DDT from past DDT pollution. In this study, a
      chromatographic procedure for the determination of the enantiomeric fractions of
      o,p'-DDT based on heart-cutting multidimensional gas chromatography was
      developed. The optimization carried out achieved low ratios of DDT degradation
      (<15%) in the chromatographic system. High selectivity and sensitivity in the
      detection of the target compounds, with a limit of detection as low as 2.1 pg
      microL(-1), was reached. In addition, high degrees of repeatability (RSD<2.0%)
      and reproducibility (RSD<3.2%) were obtained for the enantiomeric fractions
      measured in analytical standards and soil samples.

PMID- 19604511
TI  - Application of hollow fiber liquid-phase microextraction in identification of oil
      spill sources.
AB  - In this study, hollow fiber based liquid-phase microextraction (HF-LPME), coupled
      with GC, GC-MS and GC-IRMS detections, was employed to determine petroleum
      hydrocarbons in spilled oils. According to the results, the HF-LPME method
      collected more low-molecular weight components, such as C(7)-C(11)n-alkanes,
      naphthalene, and phenanthrene, than those collected in conventional liquid-liquid
      extraction (LLE). The results also showed that this method had no remarkable
      effect on the distributions of high-molecular weight compounds such as >C(18)n
      alkanes, C(1)-C(3) phenanthrene, and hopanes. Also, the carbon isotopic
      compositions of individual n-alkanes in the two preparation processes were
      identical. Accordingly, HF-LPME, as a simple, fast, and inexpensive sample
      preparation technique, could become a promising method for the identification of
      oil spill sources.

PMID- 19604512
TI  - Peak compression factor of proteins.
AB  - An experimental protocol is proposed in order to measure with accuracy and
      precision the band compression factor G(12)(2) of a protein in gradient RPLC.
      Extra-column contributions to bandwidth and the dependency of both the retention
      factor and the reduced height equivalent to a theoretical plate (HETP) on the
      mobile phase composition were taken into account. The band compression factor of
      a small protein (insulin, MW kDa) was measured on a 2.1mm x 50mm column packed
      with 1.7 microm C(4)-bonded bridged ethylsiloxane BEH-silica particles, for 1
      microL samples of dilute insulin solution (<0.05g/L). A linear gradient profile
      of acetonitrile (25-28% acetonitrile in water containing 0.1% trifluoroacetic
      acid) was applied during three different gradient times (5, 12.5, and 20 min).
      The mobile phase flow rate was set at 0.20 mL/min in order to avoid heat friction
      effects (maximum column inlet pressure 180 bar). The band compression factor of
      insulin is defined as the ratio of the experimental space band variance measured
      under gradient conditions to the reference space band variance, which would be
      observed if no thermodynamic compression would take place during gradient
      elution. It was 0.56, 0.71, and 0.76 with gradient times of 5, 12.5, and 20 min,
      respectively. These factors are 20-30% smaller than the theoretical band
      compression factors (0.79, 0.89, and 0.93) calculated from an equation derived
      from the well-known Poppe equation, later extended to any retention models and
      columns whose HETP depends on the mobile phase composition. This difference is
      explained in part by the omission in the model of the effect of the pressure
      gradient on the local retention factor of insulin during gradient elution. A much
      better agreement is obtained for insulin when this effect is taken into account.
      For lower molecular weight compounds, the pressure gradient has little effect but
      the finite retention of acetonitrile causes a distortion of the gradient shape
      during the migration of its breakthrough front along the column. This phenomenon
      should be taken into account in the theoretical models.

PMID- 19604513
TI  - Ferritin as a bionano-particulate emulsifier.
AB  - Stable 'Pickering-type' emulsions were prepared using ferritin, a spherical
      protein, as a bionano-particulate emulsifier and n-dodecane, toluene, castor oil,
      olive oil or vegetable oil as an oil phase, in the absence of any surfactant
      molecules. All the emulsions prepared were of the oil-in-water type and an
      increase of ferritin concentration decreased the volume average droplet
      diameters. Transmission electron microscopy studies of the ferritin residues
      remaining after evaporation of oil and water from the emulsion revealed a broken
      capsule morphology, which is strong evidence for the attachment of ferritin at
      the oil-water interface thereby stabilizing the emulsion. The emulsion droplets
      could be elongated and made to pass through a glass capillary.

PMID- 19604514
TI  - Photocatalytic activity of a surface-modified anatase and rutile titania
      nanoparticle mixture.
AB  - Photocatalytic activity of mixtures of anatase and rutile titania nanoparticles,
      both bare and treated via capillary condensation of a silica precursor, was
      investigated by following photodegradation of methylene blue by ultraviolet light
      in an aqueous solution. The best observed activity for the physically mixed
      nanoparticles was seen at an anatase to rutile mass ratio of 4:1. This mixture
      was subject to capillary condensation of tetraethyl orthosilicate (TEOS) at
      various saturation ratios, followed by reaction of TEOS to form silica. Treatment
      at a saturation ratio of 1.2 improved photoactivity over that of the physical
      mixture, a result attributed to enhanced interphase connectivity and increased
      methylene blue adsorption onto silica.

PMID- 19604515
TI  - Prediction models for shape and size of ca-alginate macrobeads produced through
      extrusion-dripping method.
AB  - The aim of this work was to develop prediction models for shape and size of ca
      alginate macrobeads produced through extrusion-dripping method. The relationship
      between the process variables on the shape and size of the alginate drops before
      and after gelation was established with the aid of image analysis. The results
      show that a critical Ohnersorge number (Oh)>0.24 was required to form spherical
      beads. The shape transition of ca-alginate beads could be typically distinguished
      into three phases along the collecting distance and it was affected by the
      combined influence of the solution properties, the collecting distance and the
      drop size. Mathematical equations and a master shape diagram were developed to
      reveal a clear operating region and the overall process limits within which
      spherical ca-alginate beads could be formed. In terms of bead size, the overall
      size correction factor (K) which accounted for the liquid loss factor (k(LF)) and
      the shrinkage factor (k(SF)), varied between 0.73 and 0.85 under the experimental
      conditions. The size prediction model correlated well with the experimental data.
      The approach and the outcome could be used as a model to develop prediction tools
      for similar bead production systems.

PMID- 19604516
TI  - JNK inhibitor protects dopaminergic neurons by reducing COX-2 expression in the
      MPTP mouse model of subacute Parkinson's disease.
AB  - Increasing evidence suggests that inflammation may be involved in the loss of
      dopaminergic neurons in Parkinson's disease (PD). Among inflammatory molecules,
      COX-2, a key kinase for the inflammatory response, has been suggested to play an
      important role in dopaminergic neuron loss in PD. However, the upstream molecular
      pathways of COX-2 expression remain uncertain. In the present study, we
      investigated the role of c-Jun [1] N-terminal kinase (JNK) in the process of COX
      2 expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model of subacute PD. Our data showed that MPTP induced a transient JNK
      activation of dopaminergic neurons, upregulated COX-2 expression in dopaminergic
      neurons, and caused the loss of dopaminergic neurons. We found that inhibiting
      JNK with SP600125, a special inhibitor of JNK, reduced the levels of c-Jun
      phosphorylation, blocked p-c-Jun translocation from the cytoplasm to the nucleus
      in dopaminergic neurons of substantia nigra, mitigated the loss of dopaminergic
      neurons, and improved motor function in MPTP-induced PD in C57BL/6N mice. These
      results indicate that JNK signaling pathway may be the major upstream mediator of
      regulation of COX-2 expression induced by MPTP in vivo and inhibiting JNK
      activity may represent a new and effective strategy to PD.

PMID- 19604517
TI  - Gestational high-fat programming impairs insulin release and reduces Pdx-1 and
      glucokinase immunoreactivity in neonatal Wistar rats.
AB  - Hyperglycemia and compromised beta-cell development were demonstrated in neonatal
      rats programmed with a gestational high-fat diet. The aim of this study was to
      determine whether these changes were attributed to impaired insulin release and
      altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter
      (GLUT)-2 in high-fat-programmed neonates. Fetuses were maintained, via maternal
      nutrition, on either a standard laboratory diet (control) or a high-fat diet
      throughout gestation (HFG). Pancreata from 1-day-old neonates were excised for
      islet isolation and the subsequent measurement of insulin release at 2.8, 6.5,
      13, and 22 mmol/L glucose. Other pancreata were either snap frozen for
      quantitative polymerase chain reaction or formalin fixed for immunohistochemistry
      followed by image analysis. The HFG neonates had reduced insulin release at 13-
      and 22-mmol/L glucose concentrations. No significant differences were found in
      Pdx-1, GK, or GLUT-2 messenger RNA expression. In HFG neonates, immunoreactivity
      of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction
      in GLUT-2. Gestational high-fat programming impairs insulin release and reduces
      Pdx-1 and GK immunoreactivity.

PMID- 19604518
TI  - FORT and FORD: two simple and rapid assays in the evaluation of oxidative stress
      in patients with type 2 diabetes mellitus.
AB  - The aim of the study was to evaluate the levels of free oxygen radicals and free
      oxygen radicals defense in patients with newly diagnosed type 2 diabetes mellitus
      (T2DM). The disease seems to be involved strongly in the production of reactive
      oxygen species. Forty-five patients with newly diagnosed T2DM and 20 apparently
      healthy individuals (control group) were included in the study. Reactive oxygen
      species were determined using the free oxygen radicals (FORT) test, which is
      based on the Fenton reaction. In this method, the hydroperoxides reacted with the
      transition metal ions liberated from the proteins and were converted to alkoxy
      and peroxy radicals. The radical species produced by the reaction, which are
      directly proportional to the quantity of lipid peroxides, interact with an
      additive that forms a radical molecule. Similarly, the free oxygen radicals
      defense (FORD) test uses preformed stable and colored radicals and determines the
      decrease in absorbance that is proportional to the blood antioxidant
      concentration. We found that (a) FORT levels were increased in diabetic patients
      (2.86 +/- 0.56 mmol/L H(2)O(2)) compared with controls (1.87 +/- 0.26 mmol/L
      H(2)O(2)) (P < .0001) and (b) FORD levels were lower in diabetic patients (1.23
      +/- 0.18 mmol/L Trolox) compared with controls (1.34 +/- 0.14 mmol/L Trolox) (P <
      .01). The intraassay and interassay coefficients of variation were 3.7% and 6.2%,
      respectively, for FORT and 4.2% and 6.6%, respectively, for FORD. Determination
      of free oxygen radicals and free oxygen radicals defense seems to play an
      important role in the generation and evaluation of oxidative stress, an imbalance
      between oxidants and antioxidants that can lead to oxidative damage and is
      involved in the pathogenesis of several diseases, such as T2DM.

PMID- 19604519
TI  - Delayed improvement of insulin secretion after autologous islet transplantation
      in partially pancreatectomized patients.
AB  - The purpose of this study was to evaluate the effects of autologous islet
      transplantation (ITx) on glucose homeostasis and insulin secretory function after
      partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal
      Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px
      + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx
      controls were recruited, and all groups were followed over a 24-month period.
      They performed the 75-g oral glucose tolerance test and the 1-mg glucagon
      stimulation test. Hemoglobin A(1c) was measured, and indices of insulin secretion
      were calculated. In the Px + ITx group, insulin secretion increased after a nadir
      at 6 months. Glucose tolerance, which had been abruptly impaired immediately
      after Px, recovered until 6 months and stabilized thereafter. As a result,
      differences in glucose intolerance emerged between the subjects in the Px group
      and those in the Px + ITx group at 24 months after Px. Characteristic variables
      in the better insulin secretory subjects in the Px + ITx group included younger
      age, less extensive pancreas resection, and a greater number of total islets. In
      summary, delayed amelioration of glucose intolerance was induced by autologous
      ITx after partial Px, even with a small number of islets.

PMID- 19604521
TI  - The association between normal alanine aminotransferase levels and the metabolic
      syndrome: 2005 Korean National Health and Nutrition Examination Survey.
AB  - The metabolic syndrome is known to sometimes exist in the presence of normal
      aminotransferase levels. The purpose of this study was to determine the lowest
      sex-specific level of alanine aminotransferase associated with the metabolic
      syndrome in a nationwide, representative Korean population. We analyzed data from
      adults 20 years and older (n = 3405) assessed in the Third Korean National Health
      and Nutrition Examination Survey (2005). Participants were divided into 4 groups
      according to the quartiles of alanine aminotransferase levels for each sex.
      Logistic regression modeling was performed after adjustment for age, body mass
      index, waist circumference, smoking, ingested alcohol amount, and physical
      activity. Alanine aminotransferase level groups 3 and 4 in women (> or =15 IU/L)
      and group 4 in men (> or =27 IU/L) were significantly associated with the
      metabolic syndrome compared with the lowest alanine aminotransferase groups (<16
      IU/L in men, <11 IU/L in women). In men, the odds ratio (95% confidence interval)
      of the metabolic syndrome was 2.71 (1.31-5.63) for alanine aminotransferase group
      4 (> or =27 IU/L). In women, odds ratios were 1.69 (1.02-2.80) and 2.06 (1.23
      3.43) for alanine aminotransferase groups 3 (15 < or = alanine aminotransferase <
      19 IU/L) and 4 (> or =19 IU/L), respectively. High-normal alanine
      aminotransferase levels (> or =27 IU/L in men, > or =15 IU/L in women) were
      strongly associated with the metabolic syndrome in Korean adults.

PMID- 19604520
TI  - Positive association of serum levels of advanced glycation end products and high
      mobility group box-1 with asymmetric dimethylarginine in nondiabetic chronic
      kidney disease patients.
AB  - There is accumulating evidence that engagement of the receptor for advanced
      glycation end products (RAGE) with ligands such as advanced glycation end
      products (AGEs) and high mobility group box-1 (HMGB-1) elicits vascular
      inflammation, thus contributing to the increased risk for cardiovascular disease.
      Furthermore, enhanced accumulation of asymmetric dimethylarginine (ADMA) plays a
      role in cardiovascular disease in chronic kidney disease (CKD) patients. However,
      the relationships among serum levels of AGEs, HMGB-1, soluble form of RAGE
      (sRAGE), and ADMA are largely unknown. The aim of the present study is to
      determine their relationships in CKD patients. Twenty nondiabetic normotensive
      CKD patients with dyslipidemia and 20 age- and sex-matched healthy controls were
      enrolled. All subjects underwent determination of blood chemistries; urinary
      proteinuria; and serum levels of AGEs, HMGB-1, sRAGE, and ADMA. Serum AGE, HMGB
      1, sRAGE, and ADMA levels in CKD patients were significantly higher than those in
      control subjects. Circulating levels of AGEs in CKD patients were positively
      associated with sRAGE and ADMA, and HMGB-1 with ADMA, but not sRAGE. There were
      no significant associations among these markers and serum creatinine, estimated
      glomerular filtration rate, proteinuria, and lipid levels. In multiple regression
      analyses, AGEs and HMGB-1 were independently correlated with ADMA. The present
      study demonstrated that AGE and sRAGE levels were correlated with each other and
      that AGEs and HMGB-1 were independently associated with ADMA in nondiabetic CKD
      patients. Elevation of the RAGE ligands may enhance ADMA levels, suggesting the
      active involvement of AGE/HMGB-1-RAGE-ADMA axis in CKD patients.

PMID- 19604522
TI  - Preliminary report: the effect of a 6-month dietary glycemic index manipulation
      in addition to healthy eating advice and weight loss on arterial compliance and
      24-hour ambulatory blood pressure in men: a pilot study.
AB  - We aimed to determine whether altering dietary glycemic index (GI) in addition to
      healthy eating and weight loss advice affects arterial compliance and 24-hour
      blood pressure (BP), both coronary heart disease (CHD) risk factors. Middle-aged
      men with at least 1 CHD risk were randomized to a 6-month low-GI (LGI) or high-GI
      (HGI) diet. All were advised on healthy eating and weight loss. They were seen
      monthly to assess dietary compliance and anthropometrics. Carotid-femoral pulse
      wave velocity (PWV), fasting blood lipid profile, and glucose and insulin
      concentrations were measured at baseline and at months 3 and 6. Six-hour
      postprandial glucose and insulin responses and 24-hour ambulatory BP were also
      assessed at baseline and month 6. Thirty-eight subjects (HGI group, n = 16; LGI
      group, n = 22) completed the study. At month 6, groups differed in dietary GI,
      glycemic load, and carbohydrate intake (P < .001). Fasting insulin concentration
      and insulin resistance (calculated by homeostatic model assessment) were lower in
      the LGI than the HGI group (P < .01). The reduction in total cholesterol and 24
      hour BP was bigger in the LGI than the HGI group (P < .05); and only the LGI
      group had significant reductions (P < .05) in PWV, low-density lipoprotein
      cholesterol, and triacylglycerol concentration. There were no differences in
      postprandial glucose or insulin responses between the groups. The results suggest
      that an LGI diet may be more beneficial in reducing CHD risk, including PWV and
      24-hour BP, even in the setting of healthy eating and weight loss; and thus,
      further study is warranted.

PMID- 19604523
TI  - Effect of L-carnitine on the size of low-density lipoprotein particles in type 2
      diabetes mellitus patients treated with simvastatin.
AB  - Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit
      in reducing the risk of cardiovascular events in diabetic patients. This study
      evaluated the efficacy of L-carnitine on the size of LDL particles in type 2
      diabetes mellitus patients treated with simvastatin. Eighty diabetic patients
      were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups
      received either simvastatin monotherapy 20 mg (n = 40) or L-carnitine 2 g/d and
      simvastatin 20 mg (n = 40). The following variables were assessed at baseline;
      after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting
      plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL
      subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides,
      apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2
      groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P
      < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05).
      Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P <
      .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P
      < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8%
      vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 A, P < .001) and
      HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated
      with carnitine and simvastatin showed a reduction in small-sized LDL proportion
      and an increase in LDL particle size.

PMID- 19604525
TI  - Sex differences in postprandial plasma tumor necrosis factor-alpha, interleukin
      6, and C-reactive protein concentrations.
AB  - Abdominal obesity and insulin resistance are characterized by low-level chronic
      inflammation most likely implicated in the increased cardiovascular disease risk
      associated with these conditions. However, not much is known of the acute
      regulation of circulating inflammatory markers in response to food intake. The
      aim of this study is to examine changes in inflammatory marker concentrations
      after the consumption of a high-fat meal in men and women. We measured tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein
      concentrations in plasma samples collected at 0, 4, and 8 hours after consumption
      of the meal in 39 men and 41 women. Associations between these variations and
      physical as well as metabolic variables were then examined. We noted significant
      increases in plasma IL-6 concentrations at 4 and 8 hours after the meal in men
      (+34% and +107%, respectively; P < .005 vs 0 hour) and women (+78% and +153%,
      respectively; P < .0001 vs 0 hour). Postprandial plasma TNF-alpha concentrations
      significantly dropped at 4 hours after the high-fat meal in men (-9.5%, P < .0005
      vs 0 hour) and women (-5.5%, P < .05 vs 0 hour). Plasma CRP concentrations were
      not affected by food intake in either men or women. We also found that
      postprandial plasma concentrations of IL-6 were lower in subjects with a normal
      glucose tolerance (n = 69) compared with individuals with an impaired glucose
      tolerance (n = 11). Results of the present study show that consumption of a high
      fat meal is associated with a transient reduction in circulating concentrations
      of TNF-alpha in both men and women as well as an elevation of plasma IL-6
      concentrations that was found to be greater in women than in men.

PMID- 19604524
TI  - Influence of gender on the relationship between insulin sensitivity, adiposity,
      and plasma lipids in lean nondiabetic subjects.
AB  - Individuals with obesity frequently have an atherogenic lipid profile. It has
      been proposed that the insulin resistance observed in these individuals is
      involved in the development of these lipid abnormalities. However, most studies
      that have examined the relationship between insulin resistance and lipid
      abnormalities have included subjects who are either obese and/or glucose
      intolerant, 2 factors that may affect lipid levels independent of insulin
      resistance. We have therefore examined the impact of insulin resistance on plasma
      lipids in a healthy, lean (average body mass index <24 kg/m(2)), nondiabetic
      population (N = 104). In our subjects, we observed a wide range of values for
      insulin sensitivity index (ISI) as calculated by the formula of Matsuda and
      DeFronzo. Lipid values ranged considerably in this population, but incidence of
      hypertriglyceridemia and hypercholesterolemia was low in the absence of obesity.
      We first examined the relationship between ISI and total and regional adipose
      stores as assessed by dual-energy x-ray absorptiometry. In men, we observed
      higher values for indices of total and central adipose stores that were
      significantly associated with decreased insulin sensitivity. In contrast, in
      women, ISI values were not associated with any variables related to either total
      or regional adiposity. In men, ISI was also significantly associated with higher
      triglycerides levels (P < .01) when adjusted for age and percentage of truncal
      fat. In women however, there was no significant association between ISI and
      triglycerides (P = .14). Instead, in women, total fat and truncal fat were
      independent predictors of several lipid levels. These results both highlight sex
      differences in the associations between insulin resistance, regional adipose
      stores, and lipids values and emphasize the importance of adipose stores on the
      development of an individual's lipid profile.

PMID- 19604526
TI  - Cytotoxic 16-beta-[(D-xylopyranosyl)oxy]oxohexadecanyl triterpene glycosides from
      a Malagasy plant, Physena sessiliflora.
AB  - Brine shrimp lethality assay-guided separation of the MeOH extract of leaves of
      Physena sessiliflora, which is endemic to Madagascar, afforded eight triterpene
      glycosides, Physenoside S1-4 and 16-beta-[(d-xylopyranosyl)oxy]oxohexadecanyl
      homologues, Physenoside S5-8. Structural elucidation of these compounds was based
      on both spectroscopic analyses and chemical properties. Physenoside S7 and S8
      have significant cytotoxic activities in the brine shrimp lethality assay.

PMID- 19604527
TI  - Non-volatile components of the essential oil secretory cavities of Eucalyptus
      leaves: discovery of two glucose monoterpene esters, cuniloside B and
      froggattiside A.
AB  - The essential oils extracted from the embedded foliar secretory cavities of many
      Eucalyptus species are of economic value as pharmaceuticals and fragrance
      additives. Recent studies have indicated that Eucalyptus secretory cavities may
      not be exclusively involved in the biosynthesis and storage of essential oils.
      Therefore, we selected three species upon which to perform an examination of the
      contents of foliar secretory cavities: Eucalyptus froggattii, E. polybractea and
      E. globulus. This paper describes the isolation and structural characterization
      of two non-volatile glucose monoterpene esters, which we have named cuniloside B
      and froggattiside A, from within the secretory cavities of these species, and
      shows the presence of these compounds in solvent extracts of the leaves from two
      other species of Eucalyptus. Both compounds were found in high proportions
      relative to the essential oils extracted from the leaves. We propose that many
      other carbohydrate monoterpene esters previously isolated from bulk leaf extracts
      of various Eucalyptus species may also be localized within the non-volatile
      fraction of foliar secretory cavities.

PMID- 19604528
TI  - Repeat attenders at National Health Service walk-in centres - a descriptive study
      using routine data.
AB  - OBJECTIVES: Whilst numerous studies have examined repeat attendance at general
      practices or emergency departments, little is known about repeat attenders at
      walk-in centres. The aim of this study was to examine age, gender, socio-economic
      status, distance from walk-in centre, day and time of attendance in relation to
      repeat attendance at walk-in centres. STUDY DESIGN: Descriptive study using
      routine data from four walk-in centres in England, two of which were located in
      London and were accessible to local and commuter populations. METHODS: Data for 2
      years (2003-2004) were examined. Age, gender, day and time of attendance were
      obtained from administrative records. Distance was calculated from the census
      output area of residence to walk-in centre attended. The Index of Multiple
      Deprivation (Income Domain) was used as an indicator of socio-economic
      deprivation at the small-area level. RESULTS: Thirty-nine percent of 272,701
      attendances by 166,486 patients were repeat attendances. Seventy percent of
      patients attended once, 27.9% attended two to five times, and 2.2% attended on
      over five occasions over the 2-year study period. Patients attending the two
      London walk-in centres lived closer than those attending the two walk-in centres
      outside London (percentage living 6 km or more from walk-in centre: 9% and 12%
      compared with 18% and 22%). The London walk-in centres had a higher percentage of
      single attenders (74.1% and 78%) compared with the other two walk-in centres
      (63.3% and 64.7%). Repeat attenders lived closer to walk-in centres than single
      attenders. Adjusted odds ratios for patients living within 3 km of the walk-in
      centre relative to patients living 6 km or more from the walk-in centre ranged
      from 1.59 [95% confidence interval (CI) 1.42-1.78] to 3.34 (95% CI 3.12-3.57) for
      patients attending two to five times, and from 2.37 (95% CI 1.36-4.11) to 14.99
      (95% CI 11.30-19.88) for patients with over five attendances. There was
      substantial variation with significant contrasting patterns in odds ratios across
      walk-in centres in relation to the other variables. Repeat attenders were older
      than single attenders at three of the four walk-in centres. Repeat attenders
      tended to be more likely to be male at two walk-in centres, and less likely to be
      male at the other two walk-in centres. Socio-economic deprivation tended to be
      associated with repeat attendance at one of the walk-in centres. There were also
      significant and contrasting patterns in relation to day and, to a lesser extent,
      time of attendance. CONCLUSIONS: Users living near walk-in centres are more
      likely to be repeat attenders. Age, gender, socio-economic deprivation, day and
      time of attendance had significantly higher or lower odds ratios for repeat
      attendance at different walk-in centres, suggesting that organizational and other
      factors may determine patterns of repeat attendance.

PMID- 19604529
TI  - [Diagnostic accuracy and interobserver variability in the BI-RADS ultrasound
      system].
AB  - OBJECTIVES: To determine the predictive values and the interobserver variability
      of the descriptors and diagnostic categories of the BI-RADS- Ultrasound system
      and its usefulness for predicting malignancy in solid breast nodules. MATERIAL
      AND METHODS: We evaluated 601 consecutive solid nodules in 554 patients studied
      with ultrasound. All ultrasound examinations were performed by one of the three
      radiologists that participated in the study and the static images were reviewed
      by all three radiologists independently; radiologists were blind to the clinical
      history and to the findings at mammography and at histological study. RESULTS:
      The descriptors that best predicted benignity were circumscribed margins and oval
      shape (NPV, > 96%), parallel orientation (NPV, 84%-91%), and abrupt interface
      (NPV, 81%-90%). The descriptors that best predicted malignancy were spiculated
      margins (PPV, 77%-85%), echogenic halo (PPV, 61%-71%), and nonparallel
      orientation (PPV, 53%-54%). Interobserver concordance was good for lesion shape
      (kappa=0.61), circumscribed margins (kappa=0.65), and calcifications
      (kappa=0.63). The descriptors that presented the highest prognostic values for
      malignancy were spiculated margins (OR=14.68-10.45) and nonparallel orientation
      (OR=3.95-6.17). Final assessment category 3 yielded an excellent NPV for all
      three radiologists (99%-100%). The interobserver concordance was good for
      category 5 (kappa=0.77) and for category 3 (kappa=0.68); it was moderate for
      category 4 (kappa=0.59). CONCLUSIONS: The BI-RADS- Ultrasound system helps
      differentiate benign breast lesions from malignant ones and has a good or
      moderate interobserver concordance. Final assessment category 3 yielded an
      excellent negative predictive value, making it possible to avoid biopsies in
      lesions in this category.

PMID- 19604530
TI  - [Locomotion disturbances in Huntington's disease].
AB  - In Huntington's disease (HD), perturbed locomotion occurs early in the course of
      the disease and presents numerous clinical features. The gait disorders in HD
      might best be defined as a timing disorder; however, hypokinesia (i.e. a decrease
      in stride length) also plays an important role in disturbed locomotion as HD
      progresses. Gait impairments are particularly important because they lead to an
      increased risk of falls. Falls risk factors and consequences depend on the stage
      of the disease. A satisfactory therapeutic strategy for gait impairments is a
      serious challenge: the use of a metronome during gait in HD patients does not
      effectively improve their gait. Attention deficits in HD may be a major
      determinant of this failure. The effect of antichoreic medications on gait is
      still controversial because of the absence of specific evaluation of these
      medications on gait disturbances.

PMID- 19604531
TI  - Localization of VP28 on the baculovirus envelope and its immunogenicity against
      white spot syndrome virus in Penaeus monodon.
AB  - White spot syndrome virus (WSSV) is a large dsDNA virus responsible for white
      spot disease in shrimp and other crustaceans. VP28 is one of the major envelope
      proteins of WSSV and plays a crucial role in viral infection. In an effort to
      develop a vaccine against WSSV, we have constructed a recombinant baculovirus
      with an immediate early promoter 1 which expresses VP28 at an early stage of
      infection in insect cells. Baculovirus expressed rVP28 was able to maintain its
      structural and antigenic conformity as indicated by immunofluorescence assay and
      western blot analysis. Interestingly, our results with confocal microscopy
      revealed that rVP28 was able to localize on the plasma membrane of insect cells
      infected with recombinant baculovirus. In addition, we demonstrated with
      transmission electron microscopy that baculovirus successfully acquired rVP28
      from the insect cell membrane via the budding process. Using this baculovirus
      displaying VP28 as a vaccine against WSSV, we observed a significantly higher
      survival rate of 86.3% and 73.5% of WSSV-infected shrimp at 3 and 15 days post
      vaccination respectively. Quantitative real-time PCR also indicated that the WSSV
      viral load in vaccinated shrimp was significantly reduced at 7 days post
      challenge. Furthermore, our RT-PCR and immunohistochemistry results demonstrated
      that the recombinant baculovirus was able to express VP28 in vivo in shrimp
      tissues. This study will be of considerable significance in elucidating the
      morphogenesis of WSSV and will pave the way for new generation vaccines against
      WSSV.

PMID- 19604532
TI  - Assembly of mixed rod-like and spherical particles from group I and II RNA
      bacteriophage coat proteins.
AB  - The capsids of single-stranded RNA bacteriophages show remarkable structural
      similarity. In an attempt to test whether the coat protein (CP) from one
      bacteriophage could substitute for the CP of another and form mixed particles, we
      reassembled capsids in vitro from a mixture of different RNA phage CP dimers
      together with E. coli ribosomal RNA. Surprisingly, mixing CPs from phages
      belonging to groups I and II led to appearance of rod-like particles along with
      icosahedral spherical capsids, both containing a mixture of the two CPs. Rods and
      mixed spherical capsids containing host RNA were also obtained in vivo in
      bacteria expressing simultaneously fr and GA CPs. In a co-infection of the two
      phages, however, only authentic fr and GA virions were formed. Coat protein
      mutants in the FG loop were unable to assemble into rods, suggesting that these
      loops are involved in the formation of the aberrant particles.

PMID- 19604533
TI  - Biofilm morphology as related to the porous media clogging.
AB  - Aquifer recharge for the wastewater reuse has been considered and studied as a
      promising process to cope with the worldwide water scarcity. Soil clogging by an
      excessive growth of bacteria is often accompanied with the aquifer recharge. In
      this study, biofilm morphology and hydraulic conductivity were concurrently
      characterized at two flow rates and two levels of substrate concentrations. The
      experiments were conducted using a biofilm flow cell that was filled with glass
      beads. The biofilm images taken by confocal laser scanning microscopy (CLSM) were
      quantified by textural, areal, and fractal parameters. Hydraulic conductivity was
      monitored during the experiments. The flow velocity influenced the superficial
      morphology of biofilms and initial clogging time, while the substrate
      concentration affected biofilm density and clogging rate. Three different
      clogging mechanisms were suggested depending on the flow rate and substrate
      concentration: (1) clogging at a high flow rate can be accelerated by entrapped
      and accumulated biofilms, and can be easily eliminated by high shear force, (2)
      clogging at a low flow rate can be delayed for the time of local biofilm growths
      in the narrow pore necks, but the biofilm is rigid enough not to be sloughed, and
      (3) clogging in a solution with high substrate concentrations cannot be easily
      eliminated because of the growth of dense biofilms. The depicted biological
      clogging mechanisms will play a role in supporting studies about aquifer
      recharge.

PMID- 19604534
TI  - Evaluation of host-specific Bacteroidales 16S rRNA gene markers as a
      complementary tool for detecting fecal pollution in a prairie watershed.
AB  - Our ability to identify and eliminate fecal contamination of water, now and in
      the future, is essential to reduce incidences of waterborne disease. Bacterial
      source tracking is a recently developed approach for identifying sources of fecal
      pollution. PCR primers designed by Bernhard and Field [Bernhard, A.E., Field,
      K.G., 2000a. A PCR assay to discriminate human and ruminant feces on the basis of
      host differences in Bacteroides-Prevotella genes encoding 16S rRNA. Appl.
      Environ. Microbiol. 66(10), 4571-4574] and Dick et al. [Dick, L.K., Bernhard,
      A.E., Brodeur, T.J., Santo Domingo, J.W., Simpson, J.M., Walters, S.P., Field,
      K.G., 2005. Host distributions of uncultivated fecal Bacteroidales bacteria
      reveal genetic markers for fecal source identification. Appl. Environ. Microbiol.
      71(6), 3184-3191] for the detection of human (HF183), pig (PF163) and ruminant
      (CF128) specific Bacteroidales 16s rRNA genetic markers were tested for their
      suitability in detecting fecal pollution in Saskatchewan, Canada. The sensitivity
      and specificity of these primers were assessed by testing eight raw human sewage
      samples and 265 feces from 12 different species in Saskatchewan. The specificity
      of each primer set was > or =94%. The accuracy of HF183 and PF163 to distinguish
      between the different species was 100%, whereas CF128 cross-reacted with 22% of
      the pig feces. Occurrence of the host-specific Bacteroidales markers and the
      conventional indicator Escherichia coli in relation to several enteropathogens
      was investigated in 70 water samples collected from different sites along the
      Qu'Appelle River (Saskatchewan, Canada). Human and ruminant fecal markers were
      identified in 41 and 14% of the water samples, respectively, whereas the pig
      marker was never detected in the river water. The largest concentrations in E.
      coli counts were concomitant to the simultaneous detection of HF183 and CF128.
      Thermotolerant Campylobacter spp., Salmonella spp. and Shiga toxin genes (stx1
      and stx2)-positive E. coli (STEC) were detected in 6, 7 and 63% of the water
      samples, respectively. However, none of the stx positive water samples were
      positive for the E. coli O157:H7 gene marker (uidA). Odds ratios analysis
      suggests that CF128 may be predictive for the presence of Salmonella spp. in the
      river investigated. None of the fecal indicators were able to confidently predict
      the presence of thermotolerant Campylobacter spp. and STEC.

PMID- 19604535
TI  - Inverse temperature dependence of Henry's law coefficients for volatile organic
      compounds in supercooled water.
AB  - Upon supercooling, water expels volatile organic compounds (VOC), and Henry's law
      coefficients are increasing concomitant with decreasing temperature. This
      unexpected observation was found by measuring the VOC partitioning between
      supercooled water and gas phase in the temperature range from -5 degrees C to -15
      degrees C for benzene, toluene, ethlybenzene, m-, p-, o-xylenes (BTEX), methyl
      tert-butyl ether (MTBE) and ethyl tert-butyl ether (ETBE). Aqueous standard
      solutions were analyzed using a static headspace method in combination with gas
      chromatography/mass spectrometry (GC/MS). Dimensionless Henry's law coefficients
      (K(AW)) were calculated from measurements of the concentration of the VOCs in the
      headspace above the standard solutions at temperatures between -25 degrees C and
      25 degrees C. The results show that the well known temperature dependence of
      Henry's law coefficients at temperatures above 0 degrees C is inversed upon
      decreasing the temperature below 0 degrees C and formation of supercooled water
      while decreasing the temperature to -15 degrees C. Upon further decrease of the
      temperature to -25 degrees C freezing of the supercooled water occurs. K(AW)
      values increase from 0.092 (benzene), 0.099 (toluene), 0.098 (ethylbenzene),
      0.117 (m/p-xylene), 0.076 (o-xylene), 0.012 (MTBE) and 0.014 (ETBE at 5 degrees C
      to 0.298 (benzene), 0.498 (toluene), 0.944 (ethylbenzene), 0.327 (m/p-xylene),
      0.342 (o-xylene), 0.029 (MTBE) and 0.041 (ETBE) at -25 degrees C, respectively.
      Inversion of Henry coefficients upon cooling the aqueous solutions to
      temperatures below 0 degrees C is explained by the increasing formation of ice
      like clusters in the water below 0 degrees C. The VOC are expelled from these
      clusters resulting in enhanced VOC concentrations in the gas phase upon
      supercooling. Formation of ice upon further cooling to -25 degrees C results in a
      further increase of the VOC concentrations in the gas phase above the ice. The
      findings have implications for the partitioning of VOC in clouds between the gas
      phase, supercooled water droplets, aerosol particles and ice.

PMID- 19604536
TI  - Polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls
      levels in human breast milk from different regions of Turkey.
AB  - Human breast milk offers the optimal nutrition for all infants and have been
      widely used in biomonitoring programs to assess human exposure to lipophylic
      environmental contaminants such as polychlorinated dibenzo-p-dioxins (PCDD),
      polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB). There
      are no previous reports from Turkey on chemically determined levels of PCDDs,
      PCDFs, and PCBs in human breast milk expressed as World Health Organization (WHO)
      toxic equivalents (TEQ). To get an overview of the levels of these contaminants
      in Turkish human milk, samples from 51 Turkish women living in the Ankara,
      Istanbul, Antalya, Kahramanmaras, and Afyon provinces were analyzed by high
      resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS)
      throughout 2007. The mean concentrations of WHO(PCDD/F-)TEQ and WHO(PCB-)TEQ of
      all samples from the five regions were 7.5 and 3.1 pg g(-1) on a lipid basis,
      respectively. PCDD/F concentrations ranged between 0.78 and 29.3 pg WHO-TEQ g(-1)
      fat (1.7 and 36.2 pg WHO-TEQ g(-1) fat, respectively, including PCB). Of the five
      studied locations, the lowest levels of sigmaTEQs (PCDD/F+PCB) were found in the
      Afyon (6.8 pg WHO-TEQ g(-1) fat) and the highest in the Antalya (15.6 pg WHO-TEQ
      g(-1) fat) province. The results have been discussed in terms of regions and
      PCDD/F and PCBs for which analyses had been made. The mean levels of PCDD/Fs and
      PCBs in Turkish human milk are comparable to that found in other countries.

PMID- 19604537
TI  - Assessment of removal efficiency of perfluorocompounds (PFCs) in a semiconductor
      fabrication plant by gas chromatography.
AB  - This study investigated a gas chromatographic (GC) method to assess the
      destruction or removal efficiency (DRE) of local scrubbers on five
      perfluorocompounds (PFCs), i.e., SF(6), NF(3), CF(4), C(2)F(6), and C(3)F(8),
      which are very potent greenhouse gases used in a semiconductor fabrication plant.
      Air samples taken at inlets and outlets of local scrubbers were analyzed by a
      self-constructed multi-column GC system equipped with thermal conductivity
      detection. Three packed columns were integrated into the heart-cut GC system to
      allow simultaneous analysis of the five target PFCs. The Porapak Q pre-column
      performs rough separation and cuts eluent groups to two analytical columns for
      optimal separation. The Molecular Sieve - 5A column separated NF(3), CF(4), and
      C(3)F(8) and the second Porapak Q separated SF(6) and C(2)F(6). Linearity was
      greater than 0.995 (R(2)) for the five PFCs, and the reproducibility was about 4%
      (relative standard deviation) for NF(3), and better than 0.5% for the other four
      PFCs. DRE for the combustion (CB) and electric-thermal types of local scrubbers
      was evaluated by taking into account the in-line dilution from air and fuel
      gases. Both flow and tracer methods were employed to deduce the dilution factors
      (DFs). For the tracer method, helium was employed as the tracer and injected
      upstream of the scrubbers and thus mixed with the exhaust gas. With this method,
      the DFs were determined to be in the range from 4.8 to 5.9 for the CB unit,
      significantly higher than the value of 3.3 based on the flow method. The DREs for
      the CB unit for C(3)F(8) were greater than 90% and between 40% and 50% for CF(4).

PMID- 19604538
TI  - Perivascular epithelioid cell neoplasms: pathology and pathogenesis.
AB  - This review article summarizes our current understanding of the clinical,
      pathologic, immunohistochemical, and genetic aspects of perivascular epithelioid
      cell neoplasms, a rare group of related tumors defined by both morphologic and
      immunophenotypic criteria.

PMID- 19604540
TI  - Stratigraphy, correlation, and age estimates for fossils from Area 123, Koobi
      Fora.
AB  - Geological data from the Bura Hasuma region at Koobi Fora provide important
      constraints for estimating the ages of hominin fossils recovered there, including
      the cranium KNM-ER 1813. Strata of the upper Burgi, KBS, and Okote members in
      this part of Koobi Fora reflect three depositional regimes driven by changing
      paleogeography through time. The upper Burgi and lowermost KBS sequence in the
      southern Bura Hasuma region accumulated in a lacustrine to delta front setting,
      with highly localized depositional patterns, limiting the lateral extent of
      lithostratigraphic markers. Farther north, uppermost upper Burgi through KBS
      member strata document a fluctuating lake margin, with complex facies patterns.
      This interval is marked by laterally extensive lithostratigraphic markers,
      including molluscan packstones, beach sandstones, and stromatolite beds. The
      uppermost KBS and Okote members show a transition to dominantly fluvial
      character, with localized and discontinuous accumulation. An age model for the
      richly fossiliferous Area 123 sequence demonstrates the complexity of terrestrial
      accumulation patterns. Early lacustrine and delta front accumulation is marked by
      fairly continuous sedimentation, and high accumulation rates (up to ca. 91
      cm/k.yr.). The fluctuating lake margin interval reflects lower sedimentation
      rates coupled with intervals of exposure, decreasing accumulation significantly
      (to ca. 13 cm/k.yr.). The capping fluvial interval is marked by significant
      erosion surfaces, breaks which may drop the overall accumulation rate even lower
      (ca. 0.3 cm/k.yr.). The data provided here establish a geological framework at
      odds with a recent proposal of ages considerably younger (by ca. 250 k.yr.) for
      many of the fossils from Area 123 and elsewhere. Tests of age models demonstrate
      that the younger ages are not possible. While minor refinements to age estimates
      for fossils are indicated by improved chronostratigraphic control, in the case of
      KNM-ER 1813, an age of younger than 1.78 Ma is precluded on magnetostratigraphic
      grounds.

PMID- 19604539
TI  - Revisiting the homoiology hypothesis: the impact of phenotypic plasticity on the
      reconstruction of human population history from craniometric data.
AB  - Homoiologies are homoplasies that are caused by nongenetic environmental factors.
      The homoiology hypothesis predicts that osseous regions subject to repeated
      biomechanical stress during growth should be more variable and, therefore, less
      reliable for the reconstruction of phylogeny compared with osseous regions
      relatively unaffected by stress. Previous studies based on the analysis of
      multiple primate species found that regions of the cranium subject to masticatory
      induced stress were significantly more variable than non-masticatory regions, as
      predicted by the homoiology hypothesis. However, these studies also found that
      the masticatory regions were no less reliable for reconstructing primate
      phylogenetic relationships when subjected to parsimony analysis. It was
      suggested, therefore, that homoiology may be a more potent problem for the
      reconstruction of phylogeny at the intraspecific level rather than interspecific
      phylogenetics. This suggestion was tested here using matched molecular and
      craniometric data for 12 modern human populations. The results show that, as
      predicted by the homoiology hypothesis, regions of the human cranium related to
      mastication were more variable than non-masticatory regions. However, masticatory
      regions were no less reliable for inferring human population history. Therefore,
      the results match those found from the interspecific analysis of primate species
      and do not support the suggestion that homoiology is a greater problem for the
      analysis of intraspecific taxa. The results also suggest that within-taxon
      variability cannot be relied upon to predict the phylogenetic efficacy of
      morphometric characters.

PMID- 19604541
TI  - The effects of twelve representative flavonoids on tissue factor expression in
      human monocytes: structure-activity relationships.

PMID- 19604542
TI  - A randomised study comparing the antiplatelet and antiinflammatory effect of
      clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation
      acute myocardial infarction and poor responsiveness to clopidogrel: results from
      the DOUBLE study.
AB  - INTRODUCTION: The antiplatelet effect of standard or increased clopidogrel doses
      in patients with ST- segment elevation acute myocardial infarction (STEMI) has
      never been studied. In this study we compared the antiplatelet effect of a 75 mg
      daily maintenance dose of clopidogrel with 150 mg in patients with STEMI
      undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND
      METHODS: Fifty-four patients with STEMI undergoing PCI were randomly allocated to
      receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1
      month. Platelet function, measured by 5 different assays, was determined at 3
      time points: 38+/-8 hours after the procedure, 1 week and 1 month after
      randomization. RESULTS: In group 1, mean +/- SD platelet reactivity index (PRI)
      measured with the VASP assay was 57.7+/-15.7% and 46.9+/-15.7% at 1 week and 1
      month, respectively, compared to 38.8+/-15.7% and 34.9+/-12.6% in group 2
      (p=0.0001). Same results were observed for light transmittance aggregometry,
      whole blood aggregometry and VerifyNow, but not for thromboelastometry. In
      contrast to what may be expected, the 75 mg daily maintenance dose took longer
      than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore,
      patients in group 2 had a nearly 50% reduction in C-reactive protein levels both
      at 1 week and 1 month. CONCLUSION: In patients with STEMI and poor responsiveness
      to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with
      a significant reduction of platelet aggregation and a trend towards reduced
      inflammation.

PMID- 19604543
TI  - High levels of connexin 43 mRNA in high grade astrocytomas. Study of 32 cases
      with in situ hybridization.
AB  - Gap junctions are composed of a family of evolutionarily conserved integral
      plasma membrane proteins termed connexins. The aims of the research reported here
      were (1) to evaluate the Cx43 protein and mRNA of both low histological grade and
      high histological grade astrocyte tumors; (2) to evaluate if the
      immunohistochemistry of the Cx43 protein in astrocytomas could be correlated to
      histological grade, to proliferative activity (Ki67/Mib1-index) and to
      immunolabelling of the epidermal growth factor receptor (EGFR); (3) to evaluate
      if the reduction in levels of the Cx43 protein correlates with reduction in
      levels of the Cx43 mRNA. This study showed that the immunohistochemical labelling
      of Cx43 is reduced in grade III and grade IV. Decreased gap junction-mediated
      intercellular communication corresponds to decreased Cx43 and increased cellular
      proliferation rates, as measured by immunolabelling of the Ki67 nuclear antigen.
      This study demonstrated also the persistence in high grade astrocytomas of
      elevated levels of Cx43 mRNA. The reduced levels of Cx43 protein should not to be
      ascribed to a reduced genetic transcription, but to an alteration of the post
      transcriptional mechanisms such as the regulation of its synthesis and/or the
      intracellular transport to membrane sites.

PMID- 19604544
TI  - Liver immunolocalization and plasma levels of MMP-9 in non-alcoholic
      steatohepatitis (NASH) and hepatitis C infection.
AB  - Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease. Many
      issues related to the pathogenesis of this disease remain unresolved. Because of
      NASH association with the activation of liver fibrogenesis, we examined the
      plasma levels and liver immunolocalization of matrix metalloprotease-9 (MMP-9), a
      molecule involved in the remodelling processes of fibrogenesis. In addition,
      patients with chronic hepatitis C (HCV) were analyzed. Plasma concentrations of
      MMP-9 were determined by ELISA from peripheral blood and immunohistochemistry of
      the same protein was carried out in formalin-fixed and paraffin wax-embedded
      liver specimens. The mean value of circulating concentrations of MMP-9 in healthy
      controls was 39.7 ng/ml (SD: +/-4.6). In NASH and HCV-infected patients, MMP-9
      concentrations were higher: 69.0 ng/ml (SD: +/-14.5) and 61.7 ng/ml (SD: +/
      11.0), respectively. In NASH livers, MMP-9 was mainly immunolocalized on
      neutrophils, whereas in HVC-infected livers it was mainly localized over biliary
      canaliculi, bile ducts and hepatocyte cytoplasm. The different MMP-9
      immunolocalization patterns in the examined diseases suggest the presence of a
      different pathophysiological involvement of this protease in the fibrogenesis
      underlying these diseases.

PMID- 19604545
TI  - The existence of gonadotropin-releasing hormone-like peptides in the neural
      ganglia and ovary of the abalone, Haliotis asinina L.
AB  - Gonadotropin-releasing hormone (GnRH) is a neuropeptide that is conserved in both
      vertebrate and invertebrate species. In this study, we have demonstrated the
      presence and distribution of two isoforms of GnRH-like peptides in neural ganglia
      and ovary of reproductively mature female abalone, Haliotis asinina, using
      immunohistochemistry. We found significant immunoreactivities (ir) of anti
      lamprey(l) GnRH-III and anti-tunicate(t) GnRH, but with variation of labeling
      intensity by each anti-GnRH type. lGnRH-III-ir was detected in numerous type 1
      neurosecretory cells (NS1) throughout the cerebral and pleuropedal ganglia,
      whereas tGnRH-I-ir was detected in only a few NS1 cells in the dorsal region of
      cerebral and pleuropedal ganglia. In addition, a small number of type 2
      neurosecretory cells (NS2) in cerebral ganglion showed lGnRH-III-ir. Long nerve
      fibers in the neuropil of ventral regions of the cerebral and pluropedal ganglia
      showed strong tGnRH-I-ir. In the ovary, lGnRH-III-ir was found primarily in
      oogonia and stage I oocytes, whereas tGnRH-ir was observed in stage I oocytes and
      some stage II oocytes. These results indicate that GnRH produced in neural
      ganglia may act in neural signaling. Alternatively, GnRH may also be synthesized
      locally in the ovary where it could induce oocyte development.

PMID- 19604546
TI  - Resolution of syringomyelia after release of tethered cord.
AB  - BACKGROUND: Syringomyelia is an abnormal cystic dilatation of the spinal cord
      caused by excessive accumulation of CSF. Patients can develop various neurologic
      deficits secondary to untreated syringomyelia, some of which can be permanent
      despite surgical intervention. CASE DESCRIPTION: The authors present a patient
      with syringomyelia, aortic coarctation, and tethered cord syndrome. Serial
      radiographic imaging demonstrated initial significant reduction of the thoracic
      syrinx after coarctation repair and release of tethered cord. However, subsequent
      follow-up imaging revealed partial recurrence. CONCLUSION: This case provides
      evidence of a possible cause-effect relationship between syringomyelia and
      tethered cord. It demonstrates the indication of surveillance imaging of the
      entire spine to ensure that all potential etiologies of syringomyelia are
      identified and treated. Furthermore, it illustrates the complex dynamic nature of
      syrinx physiology and reinforces the importance of serial follow-up studies after
      surgical intervention.

PMID- 19604547
TI  - Severe hypotension with intracisternal application of papaverine after clipping
      of an intracranial aneurysm.

PMID- 19604549
TI  - Isn't it time for us to "give something back?".

PMID- 19604548
TI  - Rhabdomyolysis after transnasal repair of anterior basal encephalocele.
AB  - BACKGROUND: Postoperative Rhabdomyolysis (RM) is rare after neurosurgical
      procedures. Furthermore, it has not been observed after transnasal approaches.
      The authors report a case of idiopathic RM occurring after transnasal resection
      of a sincipital encephalocele. CASE DESCRIPTION: A 32-year-old woman underwent a
      transnasal resection of a sincipital encephalocele after 6 years of intermittent
      clear nasal drainage. Postoperatively, she experienced severe back pain,
      peripheral neuropathy, associated with a markedly elevated creatinine kinase, and
      severe RM. The patient was treated with hydration and forced urine alkalization
      and treated symptomatically for her pain and neuropathy. She ultimately made a
      full recovery without complication. CONCLUSION: Rhabdomyolysis is a rare but
      known complication of neurosurgical procedures. We report the first known case
      report of RM after a transnasal procedure. Furthermore, a review of documented
      postneurosurgical cases of RM is presented and reveals that the causes and risk
      factors for this complication after neurosurgery are similar to those in other
      surgical subspecialties.

PMID- 19604550
TI  - Factors affecting the outcome after treatment for metastatic melanoma to the
      brain.
AB  - BACKGROUND: Because of the difficulties inherent to the treatment of metastatic
      melanoma to the brain including high rates of disease progression and local
      treatment failure, we attempted to determine the prognostic factors that impacted
      the outcome of these patients, and reviewed patient outcome based on primary
      treatment with either surgical resection or SRS. METHODS: A retrospective review
      identified 37 patients treated for metastatic melanoma between July 2002 and
      April 2007. Information was obtained documenting systemic disease, preoperative
      symptoms, tumor size and location, disease recurrence, primary and secondary
      treatments, and survival time. RESULTS: Two patients were alive as of March 2008.
      The median survival time for patients primarily treated with surgical resection
      was 9.7 months compared to 7.9 months for patients initially treated with SRS.
      Solitary brain metastases and the absence of both preoperative hemorrhage and
      lung metastases served as prognostic factors increasing survival in both groups.
      Four patients undergoing primary treatment with SRS required subsequent surgical
      intervention secondary to radiation necrosis (3 patients) or local recurrence (1
      patient). All 4 had lesions greater than 1.5 cm. For surgical patients, planned
      postoperative treatment with either radiosurgery or radiation therapy increased
      survival time to 12.3 months vs 7.3 months. CONCLUSIONS: Patients with positive
      prognostic factors including solitary brain lesions, absence of hemorrhage
      preoperatively, and absence of lung disease are viable candidates for aggressive,
      surgical intervention followed by adjuvant therapy with radiosurgery or
      conventional radiation therapy. Other patients should be considered for more
      conservative treatment with radiosurgery or other palliative treatments.

PMID- 19604551
TI  - Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: a
      retrospective comparison with traditional transsphenoidal microsurgery in the
      same institution.
AB  - BACKGROUND: The efficacy and the minimally invasive nature of the fully
      transnasal endoscopic procedure in the treatment of pituitary adenomas and other
      lesions of the sellar area have been widely reported in the literature. Many
      authors observed similar results in terms of the correction of hormonal
      hypersecretion in functioning pituitary adenomas using endoscopic endonasal
      surgery or the traditional microscopic technique. We report the endocrinologic
      outcome in 2 series of patients operated on at the same institution for
      functioning pituitary adenomas using these 2 different techniques. METHODS: This
      study includes 2 successive series of 60 consecutive patients presenting with a
      hormonally active pituitary adenoma operated on by the same surgeon. The surgical
      results obtained in the most recently operated group using a fully endoscopic
      endonasal technique were compared with those obtained previously using the
      traditional microsurgical transsphenoidal procedure. The classification of tumors
      into 4 grades according to Hardy was based on modern MRI and intraoperative
      findings. RESULTS: The overall remission rate of hypersecretion was 63% in the
      endoscopic group compared with 50% in the microsurgical group. The most obvious
      difference between the 2 groups was observed in noninvasive macroadenomas. In
      this specific grade of tumors, the remission rate of hypersecretion obtained
      using endoscopy was 78% compared with 43% using microsurgery. The endocrinologic
      results achieved for microadenomas were similar in the 2 groups. Postoperative
      CSF leaks occurred more frequently (6 cases) in the endoscopic group.
      CONCLUSIONS: In our experience, fully endoscopic transsphenoidal surgery for
      functioning pituitary adenomas leads to a better endocrinologic outcome for
      noninvasive macroadenomas compared to the traditional microsurgical technique.
      However, morbidity with the endoscopic technique was higher in terms of the rate
      of postoperative CSF leaks.

PMID- 19604552
TI  - Emergency endovascular stent graft and coil placement for internal carotid artery
      injury during transsphenoidal surgery.
AB  - BACKGROUND: An internal carotid artery (ICA) injury is an uncommon but
      potentially fatal complication of transsphenoidal surgery. CASE DESCRIPTION: We
      report a 61-year-old male patient with a right cavernous ICA injury sustained
      during transsphenoidal surgery and who underwent endovascular Stent graft
      placement. The ICA trapping was not indicated because of the absence of the left
      A1 on preoperative magnetic resonance angiography. During Stent graft placement,
      the ICA wall could not be completely fit with a stent due to its stiff nature and
      the carotid curve. The gap between the stent and the ICA wall was filled using a
      coiling procedure on the first postoperative day. CONCLUSIONS: Endovascular Stent
      graft placement for posttranssphenoidal carotid artery injury is a useful
      technical adjunct to the management strategy and has the potential to minimize
      the risk of having to sacrifice the ICA. In cases of incomplete reconstruction of
      the Stent graft placement due to its stiff nature and the carotid curve, an
      additional coiling procedure could be helpful to obliterate the gap between the
      stent and the ICA wall. To avoid carotid injury during transsphenoidal surgery,
      careful preoperative evaluation of vascular structures and meticulous surgical
      technique are necessary.

PMID- 19604553
TI  - Complications of posterior cranial fossa surgery--an institutional experience of
      500 patients.
AB  - BACKGROUND: The complication of the posterior fossa surgery is seldom described
      in the literature. The purposes of this retrospective study are to draw attention
      to the potential complications associated with posterior fossa surgery and to
      critically review the predisposing factors that might influence the complication
      rate. METHODS: We undertook a 10-year (1992-2002) retrospective study of all
      posterior fossa surgery performed at LSUHSC. A total of 500 patients were
      obtained from the operation database, and they were categorized into 5 groups
      based on the surgical approaches: (1) cerebellopontine angle lesion, (2)
      microvascular decompression for facial pain and spasm, (3) cerebellar lesions,
      (4) Chiari I decompression, and (5) petroclival lesions. Data collected for
      analysis included patient demographics, pathological characteristics of the
      lesions, and the postoperative complications that occurred as unexpected and
      undesirable events that prolonged hospital stay and may require surgical/medical
      intervention. RESULTS: Of the 500 patients reviewed, 220 (44%) patients had tumor
      resections at the cerebellopontine angle; 110 (22%) patients had microvascular
      decompression for trigeminal neuralgia and hemifacial spasm; 86 (17.2%) patients
      had cerebellar lesions; 60 (12%) patients had Chiari I decompression; and 24
      (4.8%) patients required transpetrosal approaches for petroclival lesions. The
      overall complication rate in our study was 31.8%, affecting 159 patients.
      Cerebrospinal fluid leaks were the most frequently encountered, presenting in 65
      (13%) patients followed by meningitis in 46 (9.2%) patients, wound infection in
      35 (7%) patients, and CN palsies in 24 (4.8%) patients. Other complications that
      were observed to develop almost exclusively in patients undergoing cerebellar
      parenchymal tumor resection included cerebellar edema in 25 (5%) patients,
      hydrocephalus in 23 (4.6%) patients, cerebellar hematoma in 15 (3%) patients, and
      cerebellar mutism in 6 (1.2%) patients. The overall mortality rate related to
      surgery was 2.6% occurring in 13 patients. CONCLUSION: Posterior fossa surgery
      involves greater morbidity and mortality and has a wider variety of complications
      than surgery in the supratentorial compartment. These complications may be
      avoided by careful perioperative planning, strict adherence to aseptic technique,
      meticulous microsurgical dissection, proper wound closure, and the judicious use
      of prophylactic agent. A thorough understanding of the patient's history,
      neurological findings, imaging studies, operative anatomy, as well as all
      potential adverse events associated with the procedure is also essential to
      minimize complications.

PMID- 19604554
TI  - Acute surgical removal of low-grade (Spetzler-Martin I-II) bleeding arteriovenous
      malformations.
AB  - BACKGROUND: Early surgical removal of cerebral AVMs is a relatively infrequent
      therapeutic option when dealing with a cerebral hemorrhage caused by AVM rupture:
      even in the case of low-grade AVMs, delayed treatment is, if possible, preferred
      because it is considered safer for patients and more comfortable for surgeons. To
      assess whether acute surgery may be a safe and effective management, we conducted
      a retrospective analysis of our early surgery strategy for ruptured low-grade
      AVMs. METHODS: We reviewed 27 patients with SM grade I-II AVM treated during 2004
      to 2008 in the acute stage of bleeding (within the first 6 days after bleed). All
      patients showed a cerebral AVM on DSA at admission, and surgical removal was
      controlled by postoperative angiography. Neurological outcomes were assessed with
      GOS. The average length of follow-up was 22 months (48-3 months). RESULTS: Before
      surgery, 16 (59%) patients showed a GCS of 8 or less, 2 of them presenting an
      acute rebleeding after first hemorrhage. All patients underwent radical AVM
      surgical removal and hematoma evacuation in a single-stage procedure. Most
      patients (78%) were operated within the first day of hemorrhage. A favorable
      functional outcome (GOS: good recovery or moderate disability) was observed in 23
      patients (85%). Mortality was 7.4%. Outcome was not significantly correlated with
      GCS at presentation and with presence of preoperative anisocoria. CONCLUSIONS:
      Early surgery for grade I-II AVMs is a safe and definitive treatment, achieving
      both immediate cerebral decompression and patient protection against rebleeding,
      reducing time of hospital stay and allowing a more rapid rehabilitative course
      whenever necessary.

PMID- 19604555
TI  - Multiple dynamic cavernous malformations in a girl: long-term follow-up.
AB  - BACKGROUND: Cavernous malformations have generally been viewed as fairly benign
      vascular lesions with low potential for causing massive hemorrhage. CASE
      DESCRIPTION: We present an interesting case of multiple CMs, several of which
      were formed de novo and exhibited aggressive biological behavior resulting in
      recurrent episodes of intracranial hemorrhage over a 10-year period. This case
      illustrates a dynamic and aggressive form of CMs. Recent advances in our
      understanding of the molecular pathogenesis of CMs implicate genetics as an
      important pathogenic factor, which is the most likely etiology of this patient's
      presentation. CONCLUSION: Special challenges exist in managing young children
      with multiple, highly aggressive CMs.

PMID- 19604556
TI  - Self-satisfaction: the lost piece of puzzle.

PMID- 19604557
TI  - Single-center experience with the Neuroform stent for endovascular treatment of
      wide-necked intracranial aneurysms.
AB  - BACKGROUND: Stent-assisted coiling is an accepted endovascular treatment (EVT)
      for wide-necked intracranial aneurysms. The Neuroform stent (Target Therapeutics,
      Fremont, Calif) is a flexible nitinol self-expandable stent that was designed to
      potentially overcome the limitations of balloon expandable coronary stents in the
      intracranial circulation. The aim of this study was to reenforce the use of this
      stent for EVT of wide-necked cerebral aneurysms. METHODS: Between March 2005 and
      March 2008, 24 patients harboring wide-necked cerebral aneurysms were treated
      with stent reconstruction of the aneurysm neck. Inclusion criteria restricted the
      group to adult patients with wide-necked intracranial aneurysms (ruptured and
      unruptured lesions). Immediate postprocedure angiography studies were performed
      to determine successful coil occlusion of the aneurysm as well as patency of the
      parent vessel. We assessed the clinical history, aneurysm dimensions, and
      technical detail of the procedures, including any difficulties with stent
      placement and deployment, degree of aneurysm occlusion, and complications.
      Clinical outcome was assessed with the Glasgow Outcome Scale (GOS). RESULTS: The
      stent was easily navigated and precisely positioned in 24 of 26 cases. However,
      technical difficulties occurred in 9 patients, including difficulties in crossing
      the stents interstice in 6 cases, inadvertent stent delivery (n = 1), and
      incapacity of stent delivery (n = 1) and incapacity of crossing the neck (n = 1).
      These latter 2 cases were classified as failures of the stent-assisted technique.
      A single procedural complication occurred, involving transient nonocclusive
      intrastent thrombus formation, which was treated uneventfully with abciximab.
      Seventeen patients experienced excellent clinical outcomes (GOS 5), with good
      outcomes (GOS 4) in 5 patients and a poor outcome (GOS 3) in 2 patients. There
      were no treatment-related deaths or neurologic complications (mean clinical
      follow-up, 12 months). Angiographic results consisted of 17 complete occlusions,
      4 neck remnants, and 3 incomplete occlusions. CONCLUSIONS: The Neuroform stent is
      very useful for EVT of wide-necked intracranial aneurysms because it is easy to
      navigate and to deploy accurately. In most cases, the stent can be deployed
      precisely, even in very tortuous carotid siphons. Although in some cases delivery
      and deployment was challenging, clinically significant complications were not
      observed.

PMID- 19604558
TI  - Microvascular repair of an injured cortical draining vein.
AB  - BACKGROUND: Cortical venous injury can occur during any intracranial procedure
      with potentially severe consequences. We describe a simple technique that allowed
      for successful repair of a large cortical draining vein. CASE DESCRIPTION: A 43
      year-old, right-handed woman presented with 6 months of headaches and progressive
      difficulty with right-sided hemiparesis. She had significant loss of hand
      coordination and writing ability. Computed tomography and MR imaging revealed a
      parasagittal meningioma in the left, posterior frontal region. The patient
      underwent craniotomy with resection of the lesion. CONCLUSION: When a cortical
      vein is injured, collateral drainage pathways may prevent the development of a
      clinical problem. Because of the unpredictability of these collateral channels,
      venous reconstruction may be feasible and even straightforward in some cases.

PMID- 19604559
TI  - Treatment with intraoperative Patent Blue V dye of refractory lymphocele after
      inguinal lymphadenectomy for squamous cell penile carcinoma.
AB  - OBJECTIVES: To evaluate the potential curative role of the intraoperative use of
      a dye, the Patent Blue V, for the treatment of refractory lymphoceles by mapping
      the lymphatic leakage and selectively ligating the opened lymphatics. Inguinal
      lymphocele is a well-known complication after inguinofemoral lymph node
      dissection for penile cancer, and a variety of curative approaches have been
      reported. METHODS: From 1995 to 2007, 40 patients had undergone partial or total
      penectomy for squamous cell cancer. Superficial inguinal lymph node dissection
      with saphenous vein sparing or deep lymph node dissection was performed in 15
      patients. It was unilateral in 14 and bilateral in 1 patient. When the
      lymphoceles were refractory to conventional therapy, ligation of the lymphatic
      vessels after mapping of the leakage with the Patent Blue V dye was the treatment
      of choice. RESULTS: Overall, 5 lymphoceles were detected in 4 patients that were
      continuously increasing in size after discharge and were treated conventionally.
      In the 2 refractory lymphoceles, we then opted for the intraoperative use of a
      dye, the Patent Blue V, to map the lymphatic leakage and selectively ligate the
      opened lymphatics. In both cases, complete resolution of the lymphoceles
      occurred. No complications were observed with this technique. CONCLUSIONS: The
      presented technique is able to cure persistent lymphoceles refractory to
      conventional treatment after inguinal lymph node dissection.

PMID- 19604560
TI  - Improved assessment of renal lesions in pregnancy with magnetic resonance
      imaging.
AB  - OBJECTIVES: To ascertain the potential utility of magnetic resonance imaging in
      providing additional clarification of those solid renal mass lesions identified
      at routine antenatal ultrasonography in early pregnancy and influencing the
      management of such lesions. METHODS: We present 7 patients in whom magnetic
      resonance imaging was used to diagnose, stage, and monitor renal lesions detected
      during pregnancy. RESULTS: Magnetic resonance imaging provided for improved
      imaging of renal mass lesions identified at antenatal ultrasonography, without
      the use of ionizing radiation, and permitted management determined by optimal
      radiographic assessment of such lesions without fetal irradiation. CONCLUSIONS:
      Magnetic resonance imaging is the most appropriate method to further investigate
      renal masses identified at routine antenatal ultrasonography early in pregnancy.

PMID- 19604561
TI  - Laparoendoscopic single-site surgery simple prostatectomy: initial report.
AB  - OBJECTIVES: To report the first case and detailed technique of laparoendoscopic
      single-site (LESS) surgery simple prostatectomy for benign hypertrophy. METHODS:
      A 67-year-old man presented with acute urinary retention requiring
      catheterization. Serum prostate-specific antigen level was 5 ng/mL, and a biopsy
      revealed benign hypertrophy with a transrectal ultrasound volume estimation of
      110 mL. LESS simple prostatectomy was performed using a single multilumen port
      inserted through a solitary 2.5-cm intraumbilical incision. Standard laparoscopic
      ultrasonic shears and needle drivers, articulating scissors, and specifically
      designed bent grasping instruments facilitated dissection and suturing. RESULTS:
      An R-port was placed intraperitoneally through a 2.5-cm intraumbilical incision.
      No extraumbilical skin incisions were made. Total operative time was 120 minutes
      and estimated blood loss was 200 mL. A closed suction drain was externalized
      through the umbilical incision. No intraoperative or postoperative complications
      occurred. Hospital stay was 2 days, the retropubic drain was removed at 3 days,
      and the catheter removed at 1 week. Specimen weight was 95 g and final pathology
      revealed benign prostatic hyperplasia. At 3 months follow-up, the patient was
      completely continent and voiding spontaneously with a Q(max.) of 85 mL/s.
      CONCLUSIONS: We demonstrate technical feasibility and describe the detailed
      surgical technique of LESS simple prostatectomy. Our initial experience suggests
      that this technique may be an alternative for large-volume benign prostatic
      hyperplasia in lieu of open surgery. Comparative studies with other surgical
      techniques will determine its place in the surgical armamentarium of benign
      prostatic hyperplasia.

PMID- 19604562
TI  - Effect of transdermal electromotive drug therapy on fibrogenic cytokine
      expression in Peyronie's disease.
AB  - OBJECTIVES: To assess the effect of transdermal electromotive drug therapy (EMDT)
      on transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor
      (bFGF) expression and their receptors in plaques in patients with Peyronie's
      disease. METHODS: Tissue was obtained from 13 patients with stable Peyronie's
      disease who had undergone plaque excision because of penile curvature. Of the 13
      patients, 7 underwent EMDT with dexamethasone, verapamil, and lidocaine as first
      line therapy before plaque excision and 6 were therapy naive. TGF-beta and bFGF
      mRNA and protein expression and that of their receptors were measured using real
      time polymerase chain reaction and Western blotting. RESULTS: The mean patient
      age was 52.83 years. The mean interval from the end of EMDT to plaque excision
      was 7.6 months, with stable disease for >or=5 months. The comparison of TGF-beta
      mRNA expression in the plaques showed no difference between the EMDT and therapy
      naive patients (P = .17). Also, TGF-beta protein expression in the plaques was
      not significantly different between the EMDT and therapy-naive patients (P =
      .443). TGF-beta receptor 1 mRNA expression in the plaques was significantly
      different between the EMDT and therapy-naive patients (P = .023), but no
      difference was found for TGF-beta receptor 2 mRNA (P = .292). The expression of
      bFGF mRNA (P = .0005) and bFGF protein expression (P = .034) in the plaques was
      significantly lower after EMDT. bFGF receptor mRNA expression (P = .619) showed
      no significant differences. CONCLUSIONS: Patients with Peyronie's had
      significantly lower bFGF mRNA and bFGF protein expression in the plaques after
      EMDT. Also, overexpression of TGF-beta protein and the TGF-beta receptor was
      identified in the EMDT plaques compared with the therapy-naive plaques.

PMID- 19604566
TI  - Is type 2 diabetes mellitus a cause of severe erectile dysfunction in patients
      with metabolic syndrome?
AB  - OBJECTIVES: To determine the effect of type 2 diabetes mellitus (T2DM) as a major
      risk factor for severe erectile dysfunction (ED) in patients with metabolic
      syndrome (MS). METHODS: The study included 93 patients aged 30-70 years who had
      MS and ED. MS patients were divided into 2 groups: 37 patients with neither T2DM
      nor abnormal fasting glucose level (group 1) and 56 patients with T2DM (group 2).
      The severity of ED was determined according to the first 5-question version of
      the International Index of Erectile Function (IIEF-5). The MS was defined
      according to the 2005 International Diabetes Federation consensus definition.
      Logistic regression analysis, t test, and chi(2) tests were used to investigate
      the impact of T2DM on ED severity. RESULTS: The mean age of the patients was 55.5
      years (P = .313). Eleven patients in group 1 (29.7%) and 42 patients in group 2
      (75%) had severe ED (IIEF-5 score <or=7; P < .001). Abnormal blood pressure (BP),
      serum high-density lipoprotein (HDL), and serum triglyceride (TG) ratios were
      found to be 48.6%, 75.7%, and 86.5% in group 1 and 51.8%, 53.6% and 73.2% in
      group 2, respectively (P(BP) = .933; P(HDL) = .053; P(TG) = .205). The IIEF-5
      scores were higher in group 1 patients than in group 2 patients (12.6 vs. 7.5;
      P(IIEF-5) < .001). Presence of T2DM was significantly associated with severe ED,
      and the relative risk was as high as 7.1 (P(T2DM) < .001). CONCLUSIONS: In our
      study, the presence of T2DM was strongly associated with severe ED in patients
      with MS. We believe that components of MS should be taken into consideration in
      the diagnosis and treatment of ED.

PMID- 19604563
TI  - William Osler, urolithiasis, and God's own medicine.
AB  - OBJECTIVES: To identify the contributions of Sir William Osler, who is regarded
      as the pre-eminent physician of his time, to urology, both objective and
      subjective. METHODS: A search of Osler's bibliography of over sixteen hundred
      publications, as well as his observations, some hitherto unpublished, on the
      episodes of renal colic that he personally experienced, was conducted. Osler was
      treated with morphine, which he characterized as "God's own medicine," and the
      origin of this description is explored. RESULTS: Osler published over 50 articles
      devoted to urologic topics, including 2 on vaginismus and Peyronie's disease; the
      former, by his fun loving alter ego, Egerton Yorrick Davis, was a hoax. Osler
      discusses urolithiasis and renal colic in his magnum opus, The Principles and
      Practice of Medicine, citing Montaigne's self description of his suffering as
      "unexcelled." Osler later personally experienced 2 episodes of renal colic, which
      he graphically and eloquently describes in his Lumleian Lectures of 1910. His
      descriptions of renal colic before and after his own experience are compared in
      the light of Plato's comment that a physician should experience the disease that
      he treats. CONCLUSIONS: William Osler was one of those giants who, in the early
      days of specialization, took all of medicine for their own. His contributions to
      urology were significant and include his descriptions of his own episodes of
      renal colic and the use of morphine-"God's own medicine."

PMID- 19604568
TI  - Establishing evidence for change in ovarian cancer surgery--proposing clinical
      trials of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      (HIPEC) in ovarian cancer peritoneal carcinomatosis.

PMID- 19604567
TI  - The prognostic significance of the SUVmax (maximum standardized uptake value for
      F-18 fluorodeoxyglucose) of the cervical tumor in PET imaging for early cervical
      cancer: preliminary results.
AB  - OBJECTIVE: The objective of this study was to evaluate the prognostic
      significance of the cervical tumor uptake of fluorine-18-labeled FDG
      (fluorodeoxyglucose) measured as the SUVmax (maximum standardized uptake value)
      by PET (Positron Emission Tomography) in patients with early cervical cancer
      treated with surgery+/-adjuvant therapy. METHODS: Forty-four patients (FIGO
      clinical stage IB to IIA) with biopsy-proven cervical cancer underwent PET before
      surgery. The SUVmax of the primary cervical tumor mass was obtained and compared
      with pathological prognostic factors after the initial treatment. In addition, we
      investigated the recurrence pattern according to the SUVmax and analyzed
      independent risk factors associated with the recurrence of disease. RESULTS:
      According to the tumor stage, the mean SUVmax significantly differed among groups
      (P=0.013). The SUVmax was significantly higher in patients with deep stromal
      invasion (>or=1 cm, P=0.0208), LVSI (lymph-vascular space invasion) (P=0.0429)
      and a pathologically confirmed large tumor size of more than 4 cm (P=0.0074) when
      compared to controls. Patients with a high SUVmax (>or=13.4) had a significantly
      reduced disease-free survival rate compared to patients with a low SUVmax
      (P=0.021). In addition, the SUVmax (>or=13.4) was a significant independent
      predictor of recurrence of cervical cancer after treatment with surgery (+/
      adjuvant therapy) (P=0.0207). CONCLUSION: Patients with early cervical cancer
      showing a high SUVmax (>or=13.4) of the cervical tumor should be considered at
      increased risk for disease recurrence after surgery and may need more aggressive
      multimodal treatment.

PMID- 19604569
TI  - Effect of PVP on sperm capacitation status and embryonic development in cattle.
AB  - The objective of this study was to investigate the effects of
      polyvinylpyrrolidone (PVP) on sperm capacitation status and embryonic development
      in cattle (Bos taurus). Acrosome-reacted sperm (chlortetracycline stain) and the
      fertilization rate after intracytoplasmic sperm injection (ICSI) were enhanced
      (P<0.05) when sperm were cultured in a medium containing 10% PVP. However,
      injection of bovine in vitro-produced (IVP) embryos with medium containing 10%
      PVP suppressed development of these embryos to the 2-cell, morula, and blastocyst
      stages and cell number at the blastocyst stage (P<0.01) but did not affect
      chromosomal integrity (P>0.05). Embryo developmental capacity differed (P<0.01)
      among PVP from three suppliers, but there were no significant differences among
      three solvent media. The PVP remained localized in 40.9% of PVP-injected IVP
      embryos. In conclusion, PVP affected the acrosome reaction and enhanced the
      fertilization rate after ICSI. However, PVP remained detectable in IVP embryos
      and suppressed their developmental capacity.

PMID- 19604570
TI  - The degree of resistance to freezing-thawing is related to specific changes in
      the structures of motile sperm subpopulations and mitochondrial activity in boar
      spermatozoa.
AB  - The main aim of this work was to analyze the possible relationship between the
      structures of motile-sperm subpopulations and boar (Sus scrofa domesticus) sperm
      resistance to freezability. For this purpose, 45 boar ejaculates were subjected
      to a standard freezing-thawing protocol, and afterwards they were classified into
      three groups, in accordance with their resistance to freezing-thawing. Our
      analysis yielded four separate motile-sperm subpopulations in all of the studied
      ejaculates, both in fresh samples and after freezing-thawing. Furthermore,
      whereas curvilinear velocity (VCL), mean velocity (VAP), and dance (DNC) of sperm
      from Subpopulation 1 underwent significant increases after freezing-thawing in
      samples with a good response to freezing-thawing, the same parameters of
      Subpopulation 1 either did not undergo significant variations (VCL and DNC) or
      even showed a decrease (VAP) (from 20.4+/-0.4 microm/sec in fresh samples to
      15.2+/-2.2 microm/sec after freezing-thawing) in samples with the poorest
      response. Similarly, the behavior of other motility parameters in each
      subpopulation was also very different in the worst samples when comparing them
      with those with a good or average response to cryopreservation. Additionally, the
      DNC of all four subpopulations was in all cases lower in samples with the poorest
      characteristics of freezability. This was not the only difference, and
      significant changes in parameters such as the VCL of Subpopulations 2 and 4,
      linearity coefficient (LIN) of Subpopulations 1, 2, and 3, and wobble coefficient
      (WOB) of Subpopulations 2 and 3 were also observed in samples with different
      response to freezing-thawing. Meanwhile, the determination of mitochondrial
      activity and mitochondrial-linked reactive oxygen species formation indicated
      that the samples with the poorest freezability characteristics were also those
      with the lowest mitochondrial activity. We conclude that boar ejaculate
      resistance to cryopreservation seems to be related to the specific, initial
      motile-sperm subpopulation structure. In turn, this structure would be closely
      related to the specific, overall mitochondrial activity, which would be a very
      important indicator of sperm function. Furthermore, and as a practical
      conclusion, an in-depth analysis of motile sperm subpopulation structure together
      with functional tests could improve the design of predictive strategies for the
      freezability of boar sperm.

PMID- 19604571
TI  - Single-layer centrifugation with Androcoll-E can be scaled up to allow large
      volumes of stallion ejaculate to be processed easily.
AB  - The objective of the current study was to optimize the volumes of Androcoll-E and
      sperm sample used in various sizes of centrifuge tube to scale up single-layer
      centrifugation (SLC) for routine use in the field. Although sperm suspensions of
      equivalent quality were produced using Androcoll-E in small and large tubes, the
      sperm yield was much lower in the latter (P<0.001). In contrast, in 200-mL tubes
      (XL), the yields were approximately 25% higher than those for the small tubes. An
      increased volume (4.5 mL) of extended ejaculate in small tubes (SLC-Inc) or 15 to
      18 mL extended ejaculate on 15 mL of colloid of a reduced density, Androcoll-E
      Large (SLC-Large), in 50-mL tubes were both found to give similar yields of
      motile spermatozoa as that of the SLC-Small method (SLC-Small, 49.7+/-18.6%; SLC
      Inc, 53.3+/-17.1%; SLC-Large, 44.9+/-18.3%) and were found to be equivalent in
      quality (motility: 88.0+/-8.8%, 84.0+/-3.5%, 90.0+/-5.4%; normal morphology:
      69.4+/-17.0%, 69.4+/-12.7%, 63.9+/-15.6%; viability: 78+/-16.7%, 83.8+/-12.5%,
      80.05+/-14.6%; DNA fragmentation index: 14.7+/-10.9%, 12.8+/-8.1%, 11.6+/-7.6%,
      respectively). The processing of an "average" stallion Equus caballus ejaculate
      in approximately twenty-seven 10-mL tubes (SLC-Inc) or eight 50-mL tubes (SLC
      Large) is feasible, the latter being considered more practical for on-stud use.

PMID- 19604572
TI  - Failure to transmit scrapie infection by transferring preimplantation embryos
      from naturally infected donor sheep.
AB  - The objective of the study was to examine whether or not the preimplantation
      embryo can act as a carrier of classic scrapie infection. The study was carried
      out on quarantined premises with sheep of highly susceptible scrapie genotypes.
      Uninfected embryos, collected from New Zealand-derived Suffolk ewes, were
      surgically transferred into recipient ewes that were also of New Zealand origin.
      Seventeen negative control lambs were born on the study premises from these
      embryo transfers. Thirty-nine experimental lambs were from embryos collected from
      naturally infected donor ewes. The experimental lambs were also born on the study
      premises after their surgical transfer into recipient ewes of New Zealand origin.
      These embryos had been collected from donor ewes in a scrapie-infected flock
      where the ewes were clinically sick with scrapie or developed clinical scrapie
      after embryo collection. All lambs were confirmed as scrapie susceptible of the
      ARQ/ARQ genotype. Twenty-eight experimental animals survived to the end point of
      the study at 5 yr of age with a mean survival of 1579 d. In the negative control
      group, 12 of 17 sheep survived to 5 yr of age with a mean survival of 1508 d.
      Postmortem examinations were carried out on all animals derived by embryo
      transfer, and in none was histologic or immunohistochemical evidence of scrapie
      found. In contrast, in the originating flock the majority of scrapie cases
      occurred in ARQ/ARQ genotyped animals where a 56% mortality from scrapie had been
      recorded in animals of this genotype. Thus, the study provides no evidence for
      transmission of scrapie and reinforces published evidence that vertical
      transmission of scrapie may be circumvented by embryo transfer procedures.

PMID- 19604573
TI  - Biodegradation of a dental resin material by fibroblast conditioned media.
AB  - OBJECTIVE: Hydrolytic activity is increased in conditioned media from human
      gingival and pulp fibroblasts in response to exposure to triethyleneglycol
      dimethacrylate (TEGDMA). The purpose of this study was to determine if this
      conditioned media with hydrolytic activity could cause the biodegradation of a
      dental resin material. METHODS: Resin material specimens were stored for 30 days
      at 37 degrees C in distilled water, unconditioned media, artificial serum,
      conditioned media from human gingival and pulp fibroblasts and conditioned media
      from human pulp and gingival fibroblasts that were exposed to TEGDMA. The media
      was exchanged every other day. The specimens were subjected to Fourier transform
      infrared spectroscopy (FTIR) before and after storage. The area under the
      carbonyl peak was calculated for all the specimens to determine the extent of the
      degradation. RESULTS: Differences before and after storage in the area under the
      carbonyl peak were statistically significant for the specimens stored in the
      conditioned media from the fibroblasts that were exposed to TEGDMA. All of the
      other specimens did not produce differences in the area under the carbonyl peak
      that were statistically significant when comparing the before and after storage
      results. SIGNIFICANCE: The biodegradation demonstrated here could contribute to
      the marginal leaking seen clinically with the use of resin materials in dental
      restorations.

PMID- 19604574
TI  - Late donor cardiectomy after paediatric heterotopic cardiac transplantation.
AB  - BACKGROUND: Cardiac transplantation is a life-saving procedure in infants and
      children with advanced cardiomyopathy. However, it is greatly limited by shortage
      of paediatric donors and the complications of long-term immunosuppression,
      including post-transplant lymphoproliferative disorder (PTLD). We report the
      management of an infant who had heterotopic cardiac transplantation for advanced
      cardiomyopathy with secondary pulmonary hypertension who developed seemingly
      incurable PTLD. METHODS: An 8-month-old girl presented in 1994 with signs of
      severe heart failure, secondary to dilated cardiomyopathy. At age 11 months, the
      patient underwent a heterotopic cardiac transplantation. FINDINGS: The patient
      developed many episodes of PTLD associated with Epstein-Barr virus infection that
      were resistant to several therapies, including reduction of immunosuppression.
      Native heart recovery enabled removal of the donor heart 10.5 years after the
      original operation to allow complete cessation of immunosuppression. Her
      postoperative course was uncomplicated and the outcome was excellent. 3.5 years
      after surgery, the patient remains well, in complete remission from her PTLD, and
      has normal cardiac function. INTERPRETATION: This case shows several issues
      relating to the use of heterotopic cardiac transplantation in infants and the
      capacity of the heart to recover. It also provides new insights into the
      interaction between the immune system with several aspects of modern management
      of post-transplantation PTLD. FUNDING: None.

PMID- 19604575
TI  - Toxicity of metal mixtures to the Pacific white shrimp Litopenaeus vannamei
      postlarvae.
AB  - According to the literature, the safe level of a toxic substance for any given
      organism may be calculated from its median lethal concentration multiplied by a
      suitable application factor (AF: usually 0.1 and 0.01). The medial lethal
      concentrations for Litopenaeus vannamei postlarvae exposed to the mixtures in
      equitoxic proportions of Cd-Hg, Hg-Zn and Hg-Pb were close to one order of
      magnitude lower than the values calculated from individual toxicity tests,
      indicating a synergistic effect, while the mixture Cd-Zn showed an antagonistic
      effect. Exposure to the mixture of Cu, Fe, Mn, Zn, Cd, Hg and Pb caused 63.3% and
      100% mortality after 21 and 13 days for 0.05 and 0.1 AF, showing that
      environmental safe concentrations of toxicants should not be calculated from
      individual toxicity tests.

PMID- 19604576
TI  - The assembly of a short linear natural cytosine-phosphate-guanine DNA into
      dendritic structures and its effect on immunostimulatory activity.
AB  - DNA containing unmethylated CpG dinucleotides, or CpG motifs, (CpG DNA) has been
      explored as a therapeutic agent, owing to its potent immunostimulatory activity.
      A previous study showing that Y-shaped (Y-) CpG DNA has a high immunostimulatory
      activity compared with single- or double stranded CpG DNA suggests the
      possibility that CpG DNA in a more complicated structure is a stronger activator
      of the immune system. In the present study, dendrimer-like DNA (DL-DNA) was
      prepared by ligating Y-DNA monomers. The DL-DNA of the second or third generation
      with 12 or 24 highly potent CpG motifs in one unit, respectively, were designed
      and successfully prepared for the first time. These DL-DNAs induced greater
      amounts of tumor necrosis factor-alpha and interleukin-6 from RAW264.7 macrophage
      like cells than did a mixture of Y-DNA with the same sequences as the
      corresponding DL-DNA. DL-DNA was more efficiently taken up by RAW264.7 cells than
      Y-DNA, but the increase was lower than that exhibited by the levels of cytokine
      release. These results suggest that the dendritic structure formation is a
      potential approach to increasing the immunostimulatory activity of CpG DNA
      without any modifications of the chemical structure of the natural phosphodiester
      DNA.

PMID- 19604577
TI  - Placental chloride channels: a review.
AB  - The human placental syncytiotrophoblast (hSTB) is a polarized epithelial
      structure, that forms the main barrier to materno-fetal exchange. The chloride
      (Cl(-)) channels in other epithelial tissues contribute to several functions,
      such as maintenance of the membrane potential, volume regulation, absorption and
      secretion. Additionally, the contributions of Cl(-) channels to these functions
      are demonstrated by certain diseases and knock-out animal models. There are
      multiple lines of evidence for the presence of Cl(-) channels in the hSTB, which
      could contribute to different placental functions. However, both the mechanism by
      which these channels are involved in the physiology of the placenta, and their
      molecular identities are still unclear. Furthermore, a correlation between
      altered Cl(-) channels functions and pathological pregnancies is beginning to
      emerge. This review summarizes recent developments on conductive placental
      chloride transport, and discusses its potential implications for placental
      physiology.

PMID- 19604578
TI  - Pathways of abnormal stress-induced Ca2+ influx into dystrophic mdx
      cardiomyocytes.
AB  - In Duchenne muscular dystrophy, deficiency of the cytoskeletal protein dystrophin
      leads to well-described defects in skeletal muscle, but also to dilated
      cardiomyopathy, accounting for about 20% of the mortality. Mechanisms leading to
      cardiomyocyte cell death and cardiomyopathy are not well understood. One
      hypothesis suggests that the lack of dystrophin leads to membrane instability
      during mechanical stress and to activation of Ca2+ entry pathways. Using
      cardiomyocytes isolated from dystrophic mdx mice we dissected the contribution of
      various putative Ca2+ influx pathways with pharmacological tools. Cytosolic Ca2+
      and Na+ signals as well as uptake of membrane impermeant compounds were monitored
      with fluorescent indicators using confocal microscopy and photometry. Membrane
      stress was applied as moderate osmotic challenges while membrane current was
      quantified using the whole-cell patch-clamp technique. Our findings suggest a
      major contribution of two primary Ca2+ influx pathways, stretch-activated
      membrane channels and short-lived microruptures. Furthermore, we found evidence
      for a secondary Ca2+ influx pathway, the Na+-Ca2+ exchange (NCX), which in
      cardiac muscle has a large transport capacity. After stress it contributes to
      Ca2+ entry in exchange for Na+ which had previously entered via primary stress
      induced pathways, representing a previously not recognized mechanism contributing
      to subsequent cellular damage. This complexity needs to be considered when
      targeting abnormal Ca2+ influx as a treatment option for dystrophy.

PMID- 19604579
TI  - Flow cytometric detection of human telomerase reverse transcriptase (hTERT)
      expression in a subpopulation of bone marrow cells.
AB  - Telomerase activity has been found in most common cancers, thus indicating that
      telomerase detection may be a useful marker in cancer diagnosis. The telomeric
      amplification protocol (TRAP) assay and RT-PCR are customarily used to detect
      telomerase activity and the expression of the associated genes in cells. However,
      these methods do not provide any information about telomerase activation at an
      individual cell level. To analyze cells separately, those cells have to be
      isolated by sometimes complicated method. The immunohistochemical detection of
      human telomerase reverse transcriptase (hTERT) is useful to detect telomerase
      positive cells in a background of non-cancerous cells. A method has been
      developed for the detection of intranuclear hTERT protein, in a subpopulation of
      hematopoietic cells, using concurrent staining of a cell surface antigen and
      multicolor flow cytometry. Only mouse monoclonal anti-hTERT antibody demonstrated
      the specific positivity in immunocytochemistry and immunofluorescent flow
      cytometry. Human leukemia and myeloma cell lines showed 100% positivity, whereas
      normal neutrophils showed 0% positivity. hTERT expression was analyzed in
      hematopoietic precursor cells of bone marrow samples using concurrent staining of
      surface CD34 antigen and intracellular hTERT protein and multi-parameter flow
      cytometry. CD34 positive cells demonstrated higher expression of hTERT than CD34
      negative cells. A quick, easy and sensitive assay for determining the hTERT
      protein expression has been developed. Using this method and the multi-parameter
      nature of flow cytometry and its ability to identify cellular subpopulations will
      provide a better understanding of the mechanisms regarding the activation of
      telomerase.

PMID- 19604580
TI  - Temporal variation of heavy metal contamination in fish of the river lot in
      southern France.
AB  - The present study aims at assessing the current situation of the heavy metal
      contaminated River Lot (SW France). Several fish species were captured in October
      1987 and 2007 at three sampling sites. The concentration of copper, zinc, cadmium
      and lead were quantified in fish muscle and liver as well as in environmental
      samples (water, sediment, moss). The decrease in heavy metal concentrations in
      fish tissue between 1987 and 2007 reflects the decrease of heavy metal
      concentrations in the environment. Concentrations found in 2007 are comparable to
      those published by a study conducted in the 1990s. The situation of the River Lot
      has improved over the last 2 decades, although there is still margin for
      amelioration according to US EPA criterion to protect freshwater aquatic life.
      The average concentrations of cadmium in fish muscle in 2007 were above the
      maximum safe for human consumption defined by the European Commission.

PMID- 19604581
TI  - Creating a front porch in systems of care: improving access to behavioral health
      services for diverse children and families.
AB  - Despite recognition of the central role that service accessibility (and
      availability) should assume within a system of care, the definition proposed in
      the feature article of this special issue does not identify specific factors that
      systems of care must take into account in order to serve diverse children with
      serious emotional disturbance and their families in a culturally competent
      manner. This paper provides support for inclusion of the concepts of access and
      availability in the system of care definition and presents important factors that
      systems of care must take into account in order to increase access in a
      culturally competent manner, a core system of care value.

PMID- 19604583
TI  - Infants can rapidly learn words in a foreign language.
AB  - The present study used an object manipulation task to explore whether infants are
      able to learn words in a foreign language. French-learning 20-month-olds, who
      were taught new words in either English or French by a bilingual French-English
      speaker, succeeded in both language conditions.

PMID- 19604584
TI  - Outcomes of an integrated cognitive behaviour therapy (CBT) treatment program for
      co-occurring depression and substance misuse in young people.
AB  - BACKGROUND: There are high rates of co-occurring depression among young people
      with substance use disorders. While there is preliminary evidence for the
      effectiveness of integrated cognitive behaviour therapy (CBT) in combination with
      antidepressants among alcohol and substance dependent adolescents and adults with
      co-existing depression, no studies have examined the effectiveness of integrated
      CBT interventions in the absence of pharmacotherapy. The aim of the current study
      was to determine the outcomes of an integrated CBT intervention for co-occurring
      depression and substance misuse in young people presenting to a mental health
      setting. METHODS: Sixty young people (aged 15 to 25), with a DSM-IV diagnosis of
      Major Depressive Disorder and concurrent substance misuse (at least weekly use in
      the past month) or disorder were recruited from a public youth mental health
      service in Melbourne, Australia. Participants received 10 sessions of individual
      integrated CBT treatment delivered with case management over a 20-week period.
      RESULTS: The intervention was associated with significant improvements in
      depression, anxiety, substance use, coping skills, depressive and substance use
      cognitions and functioning at mid- (10 weeks) and post- (20 weeks) treatment.
      These changes were maintained at 6 months follow-up (44 weeks). CONCLUSIONS:
      These results provide preliminary evidence for the effectiveness of the
      integrated CBT intervention in young people with co-occurring depression and
      substance misuse. Further studies using randomised controlled designs are
      required to determine its efficacy.

PMID- 19604582
TI  - Induction of cytochrome P450 1A1 in MCF-7 human breast cancer cells by 4
      chlorobiphenyl (PCB3) and the effects of its hydroxylated metabolites on cellular
      apoptosis.
AB  - Several studies suggest an involvement of PCBs in breast cancer formation, but
      the results are ambiguous and the mechanisms not clear. We propose that local
      activation of cytochrome P450 enzymes, CYP1A1 and CYP1B1 by PCB3, may generate
      active metabolites which affect apoptosis and thereby promote mammary
      carcinogenesis. To test this hypothesis MCF-7 human breast cancer cells were
      exposed to 300 nM PCB3 and its hydroxylated metabolites, 4OH-PCB and 3,4diOH
      PCB3. The enzyme activity for CYP1A1 was assayed using the EROD assay, and CYP1A1
      and CYP1B1 protein expression by western blotting. PCB3 increased CYP1A1 activity
      (~1.5fold) and protein levels within 6h after exposure. No effect on CYP1B1
      protein expression was observed. The effects of PCB3 and both its metabolites on
      staurosporine-induced apoptosis were determined by measuring DNA fragmentation
      using ELISA and TUNEL assays, and by measuring caspase-8 and caspase-9 activity.
      We found that PCB3 and both of its hydroxylated metabolites had no effect on
      caspase-8 and caspase-9 activity when cells were grown in medium deprived of
      estrogen, but reduced caspase-9 activity when cells were grown in medium
      supplemented with serum containing estradiol. Interestingly, a decrease of DNA
      fragmentation was observed upon treatment with 3,4diOH-PCB3 in both culture
      conditions, suggesting that 3,4diOH-PCB3 affects a caspase-independent pathway of
      cell death. In summary, interactions of PCB3 and its metabolites with estradiol
      by yet unknown mechanisms inhibit caspase 9-related apoptosis and additional,
      other death pathways are affected by the catechol metabolite 3,4diOH-PCB3. These
      anti-apoptotic effects and the change in metabolic activity may contribute to the
      carcinogenic effect of PCBs.

PMID- 19604585
TI  - Treatment of persistent post-adenoidectomy velopharyngeal insufficiency by
      sphincter pharyngoplasty.
AB  - OBJECTIVE: Persistent hypernasality after adenoidectomy is an infrequent problem
      in children with normal palate. However if it happened, it can render a child's
      speech unintelligible resulting in serious affection of social life. We aimed in
      this study to identify the causes of persistent post-adenoidectomy velopharyngeal
      insufficiency and to assess the efficacy of sphincter pharyngoplasty in the
      treatment of such problem. METHODS: This study was conducted on 18 patients
      complained of hypernasal speech following removal of their adenoids after
      variable periods of failed expected spontaneous improvement. Their hypernasality
      was rated as being mild, moderate and severe, all cases were subjected to
      conservative treatment in the form of speech therapy for 3 months to correct the
      problem, and patients that did not respond to speech therapy were subjected to
      surgical intervention in the form of sphincter pharyngoplasty. Velopharyngeal
      closure was assessed using flexible nasopharyngoscopy, while speech was assessed
      using auditory perceptual assessment and nasometry. RESULTS: Hypernasality was
      mild in 9 cases, moderate in 7 cases and severe in 2 cases. Flexible
      nasopharyngoscopy showed occult submucous cleft in 5 cases, short palate in 2
      cases, and deep nasopharynx in 3 cases. Speech improvement was achieved in 8
      cases after completion of speech therapy program (all had mild hypernasality with
      no anatomical palatal defects). Ten patients that had palatal defects were
      subjected to sphincter pharyngoplasty, 8 of them showed complete recovery, while
      2 cases with severe hypernasality showed partial improvement of their speech.
      CONCLUSIONS: Persistent post-adenoidectomy velopharyngeal insufficiency may be
      due to anatomical abnormalities of the palate such as an occult submucous cleft,
      short palate or deep nasopharynx; such conditions may be overlooked during the
      preoperative preparation for adenoid removal. Speech therapy is an effective
      method in mild hypernasality especially if there is no anatomical abnormality,
      while surgical correction is usually needed in moderate and severe cases, and
      sphincter pharyngoplasty is a useful choice for those patients.

PMID- 19604586
TI  - Cadmium tolerance in seven Daphnia magna clones is associated with reduced hsp70
      baseline levels and induction.
AB  - The stress protein hsp70 is part of the intracellular alarm and repair system
      which enables organisms to counteract negative effects of toxicants on protein
      integrity. Under long-term selection pressure exerted by environmental pollution,
      in particular heavy metals, this system may be expected to play a major role in
      the course of local, microevolutionary events leading to the acquisition of
      toxicant resistance. Seven clones of Daphnia magna from different geographical
      regions were characterized regarding their sensitivity to Cd, their hsp70
      expression, and Cd accumulation. In an acute immobilisation assay, the tested
      clones showed remarkable differences in their sensitivity to Cd. The highest
      EC(50) values by far were obtained for the clone displaying lowest hsp70
      expression. In general, hsp70 levels reflected the order of sensitivity to Cd
      among the seven clones reciprocally. Clonal variations in sensitivity and hsp70
      expression could not be related to differential accumulation of Cd, though. In
      summary, the association of stress insensitivity with low hsp70 induction which
      has been exemplarily reported for populations of different invertebrates under
      strong selection pressure could be affirmed for a largely parthenogenetic species
      for the first time. Furthermore, our observation has serious consequences for the
      interpretation of toxicological assays using a single D. magna clone solely.

PMID- 19604587
TI  - Beneficial effect of reperfusion therapy beyond the preservation of left
      ventricular function in patients with acute ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: Reperfusion therapy has been shown to improve mortality in patients
      with acute ST-segment elevation myocardial infarction. However, in randomized
      clinical trials there was only a modest improvement in left ventricular ejection
      fraction with reperfusion therapy, despite a larger improvement in mortality.
      METHODS: In the prospective MITRA-Plus registry we compared 1-year mortality of
      inhospital survivors of ST-segment elevation myocardial infarction (STEMI)
      divided into nine groups with preserved (>55%), moderately reduced (41-55%) and
      severely reduced (<=40%) left ventricular ejection fraction (LVEF) and treated
      with no early reperfusion therapy, fibrinolysis or primary percutaneous coronary
      intervention (PCI) within 24 h after admission. RESULTS: A total of 5867 patients
      were included in this analysis, 1026 (18%) without early reperfusion, 2462 (42%)
      with fibrinolysis and 2379 (40%) with primary PCI. After adjustment for
      confounding variables in a propensity score analysis, reperfusion therapy (Odds
      ratio and 95% CI: 0.27, 0.15-0.48; 0.50, 0.32-0.79; 0.64, 0.44-0.93),
      fibrinolysis (Odds ratio and 95% CI: 0.27, 0.14-0.52; 0.58, 0.35-0.95; 0.60, 0.39
      0.93) and primary PCI (Odds ratio and 95% CI: 0.22, 0.11-0.44; 0.34, 0.19-0.59;
      0.56, 0.36-0.88) remained independent predictors of survival in comparison to no
      reperfusion therapy in the patients with preserved, moderately reduced and
      severely reduced LVEF, respectively. CONCLUSIONS: These results suggest a
      beneficial effect of early reperfusion therapy beyond the preservation of left
      ventricular function, however the mechanisms need further study.

PMID- 19604588
TI  - Exercise training in congenital heart disease: should we follow the heart failure
      paradigm?
AB  - Exercise intolerance is common in adults with congenital heart disease (ACHD) and
      affects their prognosis and quality of life, thus becoming an important target
      for therapies. While exercise training has been widely studied in chronic heart
      failure, its safety and efficacy in ACHD remain unknown. The main obstacle in
      studies involving physical training and when prescribing exercise, is long-term
      compliance. Lifestyle changes through behaviour modification are difficult and
      require adequate physician and patient education on the benefits and types of
      exercise. Individualised counselling regarding physical training, exercise and
      sports should begin in early adolescence or even earlier, and exercise
      restriction is rarely indicated. Self-monitoring of physical activity through
      logs and the use of simple devices such as accelerometers may also enhance
      awareness and motivation. Physicians and nurses with adequate communication
      skills should assist ACHD patients in achieving a positive attitude towards
      physical activity and lifestyle modification.

PMID- 19604589
TI  - Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel
      exchange in cancer cells.
AB  - Tumor cells fuel their metabolism with glucose and glutamine to meet the
      bioenergetic and biosynthetic demands of proliferation. Hypoxia and oncogenic
      mutations drive glycolysis, with the pyruvate to lactate conversion being
      promoted by increased expression of lactate dehydrogenase A and inactivation of
      pyruvate dehydrogenase. The NAD+ pool is consecutively regenerated and supports
      the high glycolytic flux required to produce anabolic intermediates.
      Glutaminolysis provides metabolic intermediates such as alpha-ketoglutarate to
      feed and thereby maintain the tricarboxylic acid cycle as a biosynthetic hub.
      Glycolysis and glutaminolysis share the capacity to generate NADPH, from the
      pentose phosphate pathway and through the malate conversion into pyruvate,
      respectively. Both pathways ultimately lead to the secretion of lactate. More
      than a waste product, lactate was recently identified as a major energy fuel in
      tumors. Lactate produced by hypoxic tumor cells may indeed diffuse and be taken
      up by oxygenated tumor cells. Preferential utilization of lactate for oxidative
      metabolism spares glucose which may in turn reach hypoxic tumor cells.
      Monocarboxylate transporter 1 regulates the entry of lactate into oxidative tumor
      cells. Its inhibition favors the switch from lactate-fuelled respiration to
      glycolysis and consecutively kills hypoxic tumor cells from glucose starvation.
      Combination with radiotherapy renders remaining cells more sensitive to
      irradiation, emphasizing how interference with tumor cell metabolism may
      complement current anticancer modalities.

PMID- 19604590
TI  - Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence.
AB  - DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of
      higher eukaryotes are predominantly repaired by a pathway of non-homologous end
      joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D
      NHEJ) as central components. Work carried out in our laboratory and elsewhere
      shows that when this pathway is chemically or genetically compromised, cells do
      not shunt DSBs to homologous recombination repair (HRR) but instead use another
      form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to
      characterize this repair pathway and discuss its dependence on the cell cycle as
      well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase
      III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle,
      significantly higher activity is observed in G2 phase that cannot be attributed
      to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the
      plateau phase of growth. Together, these observations uncover a repair pathway
      with unexpected biochemical constitution and interesting cell cycle and growth
      factor regulation. They generate a framework for investigating the mechanistic
      basis of HRR contribution to DSB repair.

PMID- 19604591
TI  - Comparison of conventional radiotherapy and intensity-modulated radiotherapy for
      post-operative radiotherapy for primary extremity soft tissue sarcoma.
AB  - INTRODUCTION: Doses in conventional radiotherapy for extremity soft tissue
      sarcoma (STS) potentially exceed normal tissue tolerances. This study compares 3D
      conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) in
      optimising target volume coverage and minimising integral dose to organs-at-risk
      (OAR). METHODS AND MATERIALS: Ten patients undergoing post-operative radiotherapy
      for extremity STS were assessed. PTV(1) was defined as tumour bed plus 5cm
      superiorly/inferiorly and 3cm circumferentially, PTV(2) was defined as 2cm
      isotropically. OAR were defined as whole femur, neurovascular bundle, tissue
      corridor and normal tissue outside PTV(1). For each patient 2-phase 3D-CRT was
      compared to 2/3 field (2/3f) and 4/5 field (4/5f) IMRT with simultaneous
      integrated boost (SIB). The primary planning objective was to minimise femur and
      skin corridor dose. Volumetric analysis and conformity and heterogeneity indices
      were used for plan comparison. RESULTS: A planning protocol containing
      dose/volume constraints for target and OAR was defined. 4/5f IMRT showed greatest
      conformity and homogeneity. IMRT resulted in significantly lower femur V45 using
      2/3f (p=0.01) and 4/5f (p=0.0009) than 3D-CRT. 4/5f IMRT resulted in
      significantly lower normal tissue V55 (p=0.004) and maximum dose (p=0.04) than 3D
      CRT. CONCLUSIONS: A reproducible set of planning guidelines and dose-volume
      constraints for 3D-CRT and IMRT planning for extremity sarcomas was devised. 4/5f
      IMRT with SIB resulted in better target coverage and significantly decreased OAR
      dose. Further evaluation of this technique within a clinical trial is recommended
      to demonstrate that the technical benefit of the more complex technique
      translates into patient-derived benefit by reducing late toxicity.

PMID- 19604592
TI  - Genetic diversity of the pln locus among oenological Lactobacillus plantarum
      strains.
AB  - A total of 33 Lactobacillus plantarum strains obtained from grape musts and wines
      during alcoholic and malolactic fermentations were submitted to PCR analysis with
      specific primers directed to 27 genes of the plantaricin (pln) locus previously
      described for L. plantarum strains. The number of genes that were detected varied
      depending on the strain, and cluster analysis of results rendered seven groups,
      named plantaritypes (similarity within each group >89%) that included all the 33
      oenological strains, four L. plantarum type strains (C11, NC8, J23 and J51) that
      had been previously described, and strain WCFS1 whose genome had been fully
      sequenced. The common features for most strains (74%) were the presence of the
      plnABCD regulatory system (which includes genes of the inducing peptide, its
      coupled membrane-located histidine protein kinase and two response regulators),
      the two-peptide bacteriocin plnEF genes and the genes of a membrane-bound ABC
      transport system. The pln locus is shown to be widespread among oenological
      strains (94% of appearance), as well as to possess a remarkable plasticity and
      variable regions related to its regulation and bacteriocin production.

PMID- 19604593
TI  - Epidemiology of diabetes-related lower extremity amputations in Gran Canaria,
      Canary Islands (Spain).
AB  - We have studied the rate of lower extremity amputations (LEAs) in the south of
      Gran Canaria. The incidence rate was 319.7 per 100,000 (95% CI, 258.6-380.8) per
      year in the diabetic subjects. The incidence of both diabetic and non-diabetic
      LEAs is the highest reported in Spain.

PMID- 19604594
TI  - Abnormal cold perception in the lower limbs: a sensitive indicator for detection
      of polyneuropathy in patients with type 1 diabetes mellitus.
AB  - Diabetic peripheral neuropathy differs in type 1 and type 2 diabetes. The aim of
      this study was to evaluate how signs and symptoms of neuropathy correlated with
      defects in motor and sensory nerve conduction velocity (MCV and SCV) and sensory
      perception thresholds in patients with type 1 diabetes. MCV and SCV in peroneal
      and sural nerves and vibratory, warm and cold perception thresholds (VPT, WPT,
      CPT) were evaluated in the lower limbs of 127 patients (42+/-7.9 years old,
      duration of diabetes, 16+/-11 years and HbA1c, 7.7+/-1.4%). The results were
      compared with clinical findings (neuropathy impairment assessment, NIA) and
      sensory symptoms (neurological symptom assessment, NSA). Sensory symptoms were
      present in 24% of patients, 91% had at least one abnormal finding in the
      neurological examination and 84% had abnormal nerve conduction. The greatest
      deviation from normal was observed for CPT on the dorsum of the foot and peroneal
      MCV. NIA and NSA correlated with all electrophysiological measurements in the
      foot and big toe. It is concluded that clinical findings correlate well with
      electrophysiological abnormalities in patients with type 1 diabetic neuropathy.
      An elevated CPT for the foot was the most pronounced sensory defect.

PMID- 19604595
TI  - The complexities of hepatitis C virus entry.

PMID- 19604596
TI  - Non-invasive assessment and quantification of liver steatosis by ultrasound,
      computed tomography and magnetic resonance.
AB  - Hepatic steatosis is the most prevalent liver disorder in the developed world. It
      is closely associated with features of metabolic syndrome, especially insulin
      resistance and obesity. The two most common conditions associated with fatty
      liver are alcoholic liver disease (ALD) and non-alcoholic fatty liver disease
      (NAFLD). Liver biopsy is considered the gold standard for the assessment of liver
      fat, but there is a need for less invasive diagnostic techniques. New imaging
      modalities are emerging, which could provide more detailed information about
      hepatic tissue or even replace biopsy. In the present review, available imaging
      modalities (ultrasound, computed tomography, magnetic resonance imaging and
      proton magnetic resonance spectroscopy) are presented which are employed to
      detect or even quantify the fat content of the liver. The advantages and
      disadvantages of the above-mentioned imaging modalities are discussed. Although
      none of these techniques is able to differentiate between microvesicular and
      macrovesicular steatosis and to reveal all features visible using histology, the
      proposed diagnostic modalities offer a wide range of additional information such
      as anatomical and morphological information non-invasively. In particular,
      magnetic resonance imaging and proton magnetic resonance spectroscopy are able to
      quantify the hepatic fat content hence avoiding exposure to radiation. Except for
      proton magnetic resonance spectroscopy, all modalities offer additional
      information about regional fat distribution within the liver. MR elastography,
      which can estimate the amount of fibrosis, also appears promising in the
      differentiation between simple steatosis and steatohepatitis.

PMID- 19604597
TI  - The impact of information on patient preferences in different delivery patterns:
      a contingent valuation study of prescription versus OTC drugs.
AB  - OBJECTIVES: Our analysis assessed the impact of information on patients'
      preferences in prescription versus over-the-counter (OTC) delivery systems.
      METHODS: A contingent valuation (CV) study was implemented, randomly assigning
      534 lay people into the receipt of limited or extended information concerning new
      influenza drugs. In each information arm, people answered two questions: the
      first asked about willingness to pay (WTP) for the new prescription drug; the
      second asked about WTP for the same drug sold OTC. RESULTS: We show that WTP is
      higher for the OTC scenario and that the level of information plays a significant
      role in the evaluation of the OTC scenario, with more information being
      associated with an increase in the WTP. In contrast, the level of information
      provided has no impact on WTP for prescription medicine. Thus, for the kind of
      drug considered here (i.e. safe, not requiring medical supervision), a switch to
      OTC status can be expected to be all the more beneficial, as the patient is
      provided with more information concerning the capability of the drug.
      CONCLUSIONS: Our results shed light on one of the most challenging issues that
      health policy makers are currently faced with, namely the threat of a bird flu
      pandemic. Drug delivery is a critical component of pandemic influenza
      preparedness. Furthermore, the congruence of our results with the agency and
      demand theories provides an important test of the validity of using WTP based on
      CV methods.

PMID- 19604598
TI  - Modeling the physiological glucose-insulin system on normal and diabetic
      subjects.
AB  - This paper aims to present a mathematical model to describe the plasma glucose
      and insulin daily variations on normal and diabetic subjects. The proposed model
      consists of two delay differential equations (DDEs) where five adjustable
      parameters are used to characterize the respective dynamics and oscillation
      behavior of normal and diabetic subjects. Several clinical data tests demonstrate
      that the suggested model is practical to approach the daily-life glucose dynamics
      on normal, diabetic Type 1 and Type 2 subjects. Moreover, the corresponding
      parameters are fairly persuasive to identify the patients' conditions of
      physiological functions.

PMID- 19604599
TI  - The lipid dependence of diadinoxanthin de-epoxidation presents new evidence for a
      macrodomain organization of the diatom thylakoid membrane.
AB  - The present study shows that thylakoid membranes of the diatom Cyclotella
      meneghiniana contain much higher amounts of negatively charged lipids than higher
      plant or green algal thylakoids. Based on these findings, we examined the
      influence of SQDG on the de-epoxidation reaction of the diadinoxanthin cycle and
      compared it with results from the second negatively charged thylakoid lipid PG.
      SQDG and PG exhibited a lower capacity for the solubilization of the hydrophobic
      xanthophyll cycle pigment diadinoxanthin than the main membrane lipid MGDG.
      Although complete pigment solubilization took place at higher concentrations of
      the negatively charged lipids, SQDG and PG strongly suppressed the de-epoxidation
      of diadinoxanthin in artificial membrane systems. In in vitro assays employing
      the isolated diadinoxanthin cycle enzyme diadinoxanthin de-epoxidase, no or only
      a very weak de-epoxidation reaction was observed in the presence of SQDG or PG,
      respectively. In binary mixtures of the inverted hexagonal phase forming lipid
      MGDG with the negatively charged bilayer lipids, comparable suppression took
      place. This is in contrast to binary mixtures of MGDG with the neutral bilayer
      lipids DGDG and PC, where rapid and efficient de-epoxidation was observed. In
      complex lipid mixtures resembling the lipid composition of the native diatom
      thylakoid membrane, we again found strong suppression of diadinoxanthin de
      epoxidation due to the presence of SQDG or PG. We conclude that, in the native
      thylakoids of diatoms, a strict separation of the MGDG and SQDG domains must
      occur; otherwise, the rapid diadinoxanthin de-epoxidation observed in intact
      cells upon illumination would not be possible.

PMID- 19604600
TI  - The effect of salinity on photosynthetic activity in potassium-deficient barley
      species.
AB  - The interactive effects of salinity and potassium deficiency on the growth,
      mineral elements and photosynthetic performance were investigated in wild
      (Hordeum maritimum L.) and cultivated barley (Hordeum vulgare L. var. Manel). At
      28 d of growth, plants were treated with 3 mM K and 0 mM NaCl (3-0); 3 mM K and
      100 mM NaCl (3-100); 0 mM K and 0 mM NaCl (0-0), 0 mM K and 100 mM NaCl (0-100)
      for 14 d. In both species, biomass production decreased considerably when the two
      constraints were applied simultaneously. Salinity affected shoots more than
      roots, whereas for potassium deficiency, the reverse occurred. Generally,
      potassium uptake was more affected in wild than in cultivated barley and,
      independent of potassium availability, 100 mM NaCl increased Na+ content in both
      species, whereas K+ deprivation increased Na(+) content only in H. maritimum
      shoots (0-0). Potassium-use efficiency (KUE) increased in all treated plants.
      Potassium deficiency increased the negative effects induced by salt in the
      photosynthetic process of H. vulgare, and this species seemed to be unable to
      counteract the negative effects of salinity. H. maritimum showed limitation in
      CO2 photoassimilation, but this species displayed mechanisms that play a role in
      avoiding PSII photodamage aimed to dissipate the excess energy.

PMID- 19604601
TI  - Physiological and growth changes in micropropagated Citrus macrophylla explants
      due to salinity.
AB  - Salinity is one of the major abiotic stresses affecting arable crops worldwide,
      and is the most stringent factor limiting plant distribution and productivity. In
      the present study, the possible use of in vitro culture to evaluate the growth
      and physiological responses to salt-induced stress in cultivated explants of
      Citrus macrophylla was analyzed. For this purpose, micropropagated adult explants
      were grown in proliferation and rooting media supplemented with different
      concentrations of NaCl. All growth parameters were decreased significantly by
      these NaCl treatments; this was accompanied by visible symptoms of salt injury in
      the proliferated shoots from 60mM NaCl and in the rooted shoots from 40mM NaCl.
      Malondialdehyde (MDA) increased with increasing salinity in proliferated shoots,
      indicating a rising degree of membrane damage. The concentration of total
      chlorophyll significantly decreased in the presence of NaCl, and this effect was
      more pronounced in the rooted explants. The Na(+) and Cl(-) concentrations in the
      explants increased significantly with the salinity level, but Cl(-) levels were
      higher in the proliferated explants than in the rooted explants. For osmotic
      adjustment, high concentrations of compatible solutes (proline and quaternary
      ammonium compounds-QAC) accumulated in salt-stressed plants in proliferation, but
      differences were not observed in rooted explants. In proliferation, proline and
      QAC were highly correlated with the sodium and chloride concentrations in the
      explants, indicating a possible role of these compounds in osmotic adjustment.
      The plant concentrations of NO(3)(-), K(+), Mg(2+), Ca(+) and Fe were also
      affected by the NaCl concentration of the medium. We suggest that the important
      deleterious effects in the in vitro explants of Citrus macrophylla grown at
      increasing NaCl concentrations were due mainly to toxic effects of saline ions,
      particularly Cl(-), at the cellular level.

PMID- 19604602
TI  - Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice.
AB  - We characterized the gene expression profile of brain regions at an early stage
      of the Alzheimer's like neurodegeneration in the anti-NGF AD11 model. Total RNA
      was extracted from hippocampus, cortex and basal forebrain of postnatal day 30
      (P30) and postnatal day 90 (P90) mice and expression profiles were studied by
      microarray analysis, followed by qRT-PCR validation of 243 significant
      candidates. Wide changes in gene expression profiles occur already at P30. As
      expected, cholinergic system and neurotrophins related genes expression were
      altered. Interestingly, the most significantly affected clusters of mRNAs are
      linked to inflammation and immune response, as well as to Wnt signaling. mRNAs
      encoding for different complement factors show a large differential expression.
      This is noteworthy, since these complement cascade proteins are involved in CNS
      synapse elimination, during normal brain developing and in neurodegenerative
      diseases. This gene expression pattern highlights that an early event in AD11
      neurodegeneration is represented, together with neurotrophic deficits and
      synaptic remodeling, by an inflammatory response and an unbalance in the
      immunotrophic state of the brain. These might be key events in the pathogenesis
      and development of AD.

PMID- 19604603
TI  - A novel pathway for amyloid precursor protein processing.
AB  - Amyloid precursor protein (APP) can be proteolytically processed along two
      pathways, the amyloidogenic that leads to the formation of the 40-42 amino acid
      long Alzheimer-associated amyloid beta (Abeta) peptide and the non-amyloidogenic
      in which APP is cut in the middle of the Abeta domain thus precluding Abeta
      formation. Using immunoprecipitation and mass spectrometry we have shown that
      Abeta is present in cerebrospinal fluid (CSF) as several shorter isoforms in
      addition to Abeta1-40 and Abeta1-42. To address the question by which processing
      pathways these shorter isoforms arise, we have developed a cell model that
      accurately reflects the Abeta isoform pattern in CSF. Using this model, we
      determined changes in the Abeta isoform pattern induced by alpha-, beta-, and
      gamma-secretase inhibitor treatment. All isoforms longer than and including
      Abeta1-17 were gamma-secretase dependent whereas shorter isoforms were gamma
      secretase independent. These shorter isoforms, including Abeta1-14 and Abeta1-15,
      were reduced by treatment with alpha- and beta-secretase inhibitors, which
      suggests the existence of a third and previously unknown APP processing pathway
      involving concerted cleavages of APP by alpha- and beta-secretase.

PMID- 19604605
TI  - Synthesis and characterization of the Zn(II) and Cu(II) piperidinyl isoeuxanthone
      complexes: DNA-binding and cytotoxic activity.
AB  - Two new complexes ZnL(2)x2H(2)O (1) and CuL(2)x2H(2)O (2) (HL=1-hydroxy-6-(2-(1
      piperidinyl)ethoxy)xanthone) have been synthesized and characterized. Their
      interactions with calf thymus DNA (ct DNA) were investigated by absorption
      spectroscopy, fluorescence spectroscopy, ethidium bromide (EB) displacement
      experiments, circular dichroism spectroscopy and viscosity measurements.
      Experimental results suggested that there were intercalative interactions of the
      complexes with DNA. The binding affinity of complex 2 was higher than that of 1.
      In addition, the cytotoxic effects of both complexes were evaluated with lung
      adenocarcinoma (GLC-82), esophagus squamous cancer (ECA109) and human gastric
      cancer (SGC7901) cells using MTT assay. Both were potent exhibiting significant
      cytotoxicity in vitro.

PMID- 19604606
TI  - Scoring function for DNA-drug docking of anticancer and antiparasitic compounds
      based on spectral moments of 2D lattice graphs for molecular dynamics
      trajectories.
AB  - We introduce here a new class of invariants for MD trajectories based on the
      spectral moments pi(k)(L) of the Markov matrix associated to lattice network-like
      (LN) graph representations of Molecular Dynamics (MD) trajectories. The procedure
      embeds the MD energy profiles on a 2D Cartesian coordinates system using simple
      heuristic rules. At the same time, we associate the LN with a Markov matrix that
      describes the probabilities of passing from one state to other in the new 2D
      space. We construct this type of LNs for 422 MD trajectories obtained in DNA-drug
      docking experiments of 57 furocoumarins. The combined use of
      psoralens+ultraviolet light (UVA) radiation is known as PUVA therapy. PUVA is
      effective in the treatment of skin diseases such as psoriasis and mycosis
      fungoides. PUVA is also useful to treat human platelet (PTL) concentrates in
      order to eliminate Leishmania spp. and Trypanosoma cruzi. Both are parasites that
      cause Leishmaniosis (a dangerous skin and visceral disease) and Chagas disease,
      respectively; and may circulate in blood products collected from infected donors.
      We included in this study both lineal (psoralens) and angular (angelicins)
      furocoumarins. In the study, we grouped the LNs on two sets; set1: DNA-drug
      complex MD trajectories for active compounds and set2: MD trajectories of non
      active compounds or no-optimal MD trajectories of active compounds. We calculated
      the respective pi(k)(L) values for all these LNs and used them as inputs to train
      a new classifier that discriminate set1 from set2 cases. In training series the
      model correctly classifies 79 out of 80 (specificity=98.75%) set1 and 226 out of
      238 (Sensitivity=94.96%) set2 trajectories. In independent validation series the
      model correctly classifies 26 out of 26 (specificity=100%) set1 and 75 out of 78
      (sensitivity=96.15%) set2 trajectories. We propose this new model as a scoring
      function to guide DNA-docking studies in the drug design of new coumarins for
      anticancer or antiparasitic PUVA therapy.

PMID- 19604607
TI  - Nutrition, hospital food and in-hospital mortality.

PMID- 19604604
TI  - Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide
      burden in a mouse model of Alzheimer's disease.
AB  - Accumulation of amyloid beta peptide (Abeta) in the brain is a pathological
      hallmark of Alzheimer's disease (AD); the underlying mechanism, however, is not
      well understood. In this study, we show that expression of plasminogen activator
      inhibitor 1 (PAI-1), a physiological inhibitor of tissue type and urokinase type
      plasminogen activators (tPA and uPA), increases with age in the brain of wild
      type and Abeta precursor protein-presenilin 1 (APP/PS1) transgenic mice as well
      as in AD patients. Most importantly, we show that knocking out the PAI-1 gene
      dramatically reduces Abeta burden in the brain of APP/PS1 mice but has no effect
      on the levels of full-length APP, alpha or beta C-terminal fragments.
      Furthermore, we show that knocking out the PAI-1 gene leads to increases in the
      activities of tPA and plasmin, and the plasmin activity inversely correlates with
      the amounts of SDS insoluble Abeta40 and Abeta42. Together, these data suggest
      that increased PAI-1 expression/activity contributes importantly to Abeta
      accumulation during aging and in AD probably by inhibiting plasminogen activation
      and thus Abeta degradation.

PMID- 19604609
TI  - Evaluation of Monte Carlo-based calibrations of HPGe detectors for in situ gamma
      ray spectrometry.
AB  - The aim of this work was to evaluate the use of Monte Carlo-based calibrations
      for in situ gamma-ray spectrometry. We have performed in situ measurements at
      five different sites in Sweden using HPGe detectors to determine ground
      deposition activity levels of (137)Cs from the 1986 Chernobyl accident. Monte
      Carlo-calculated efficiency calibration factors were compared with corresponding
      values calculated using a more traditional semi-empirical method. In addition,
      results for the activity ground deposition were also compared with activity
      densities found in soil samples. In order to facilitate meaningful comparisons
      between the different types of results, the combined standard uncertainty of in
      situ measurements was assessed for both calibration methods. Good agreement, both
      between the two calibration methods, and between in situ measurements and soil
      samples, was found at all five sites. Uncertainties in in situ measurements for
      the given measurement conditions, about 20 years after the fallout occurred, were
      found to be in the range 15-20% (with a coverage factor k=1, i.e. with a
      confidence interval of about 68%).

PMID- 19604608
TI  - Effects of acute gamma-irradiation on the aquatic microbial microcosm in
      comparison with chemicals.
AB  - Effects of acute gamma-irradiation were investigated in the aquatic microcosm
      consisting of green algae (Chlorella sp. and Scenedesmus sp.) and a blue-green
      alga (Tolypothrix sp.) as producers; an oligochaete (Aeolosoma hemprichi),
      rotifers (Lecane sp. and Philodina sp.) and a ciliate protozoan (Cyclidium
      glaucoma) as consumers; and more than four species of bacteria as decomposers. At
      100 Gy, populations were not affected in any taxa. At 500-5000 Gy, one or three
      taxa died out and populations of two or three taxa decreased over time, while
      that of Tolypothrix sp. increased. This Tolypothrix sp. increase was likely an
      indirect effect due to interspecies interactions. The principal response curve
      analysis revealed that the main trend of the effects was a dose-dependent
      population decrease. For a better understanding of radiation risks in aquatic
      microbial communities, effect doses of gamma-rays compared with copper,
      herbicides and detergents were evaluated using the radiochemoecological
      conceptual model and the effect index for microcosm.

PMID- 19604611
TI  - Housing wealth and mortality: A register linkage study of the Finnish population.
AB  - In many countries home ownership is the main form of property and covers a major
      part of people's possessions. Since overall wealth is difficult to measure, many
      health studies have used home ownership as an indicator of wealth and material
      resources. However, most studies have measured housing wealth with a simple
      dichotomous measure of home ownership. We examined the associations between three
      different measures of housing wealth and overall mortality, separating subsidized
      renters and private renters, and using floor area and the number of rooms as
      measures of dwelling size. We further examined whether other socioeconomic
      factors, level of urbanisation of the region of residence, and household
      composition account for the found associations. Finns aged 35-79 years at the end
      of 1999 were followed up until the end of 2004. Data were drawn from various
      registers combined by Statistics Finland and linked with death records. The age
      adjusted hazard ratio for mortality among subsidized renters compared to owner
      occupiers was 2.26 in men and 1.87 in women. However, also private renters had
      clearly higher mortality than owner-occupiers, with the excess mortality of 92%
      in men and 61% in women. Both measures of home size were also strongly associated
      with mortality, with the excess risk of 1.7-3.0 in the lowest home size quintile
      compared to the highest. Adjusting for socioeconomic factors and mutually for all
      housing wealth measures considerably attenuated the associations. Further
      adjustment for urbanisation had no effect whereas adjustment for household size,
      marital status and living arrangements attenuated the associations of the two
      home size measures and mortality. However, a clear association remained between
      all housing wealth measures and mortality after all adjustments. Housing wealth
      summarises one's material circumstances over a prolonged period of time. Measures
      of housing wealth may therefore provide useful social classifications for studies
      on poor health and mortality especially in older age groups where most deaths
      occur.

PMID- 19604610
TI  - How do long-term development and periodical changes of river-floodplain systems
      affect the fate of contaminants? Results from European rivers.
AB  - In many densely populated areas, riverine floodplains have been strongly impacted
      and degraded by river channelization and flood protection dikes. Floodplains act
      as buffers for flood water and as filters for nutrients and pollutants carried
      with river water and sediment from upstream source areas. Based on results of the
      EU-funded "AquaTerra" project (2004-2009), we analyze changes in the dynamics of
      European river-floodplain systems over different temporal scales and assess their
      effects on contaminant behaviour and ecosystem functioning. We find that human
      induced changes in the hydrologic regime of rivers have direct and severe
      consequences on nutrient cycling and contaminant retention in adjacent
      floodplains. We point out the complex interactions of contaminants with nutrient
      availability and other physico-chemical characteristics (pH, organic matter) in
      determining ecotoxicity and habitat quality, and draw conclusions for improved
      floodplain management.

PMID- 19604613
TI  - Assessment of replication of research evidence from animals to humans in studies
      on peri-implantitis therapy.
AB  - BACKGROUND: Animal research is conducted to understand the causes and treatments
      of human diseases. Clinical human studies may not, however, be able to replicate
      results previously obtained from animal experiments. AIM: to assess whether or
      not peri-implantitis therapies conducted in animal experiments were successfully
      replicated in human clinical trials. MATERIALS AND METHODS: Dental journals
      classified by citation impact factor were searched in the Journal Citation
      Reports database for animal trials on treatment of peri-implantitis between 1992
      and 2008. It was assumed that prominent findings from high-ranked journals would
      be more likely to be tested in subsequent human clinical trials. A second
      literature search was conducted in the Pubmed, Cochrane, and Lilacs databases to
      identify potential human studies that repeated or replicated animal experiments.
      Controlled trials and case-series were included in the analysis. Because of the
      heterogeneity of the studies (e.g., different study designs and different outcome
      measures), only descriptive analysis was undertaken. RESULTS: Of 1199 studies
      retrieved, 53 (23 animal and 30 human studies) were selected for the review.
      Because no animal experiment and human trial had comparable study procedures,
      precise determination of the success of replication from animal experiments in
      clinical trials was not possible. Overall, the study characteristics were
      extremely heterogeneous. CONCLUSIONS: To reduce the great heterogeneity between
      animal and human studies on peri-implantitis, researchers should pay attention to
      standardization of research procedures. Power analysis and sample-size
      calculation in animal experiments and human trials should be always considered
      when planning a research study.

PMID- 19604612
TI  - Evaluation of machinability and flexural strength of a novel dental machinable
      glass-ceramic.
AB  - OBJECTIVES: To evaluate the machinability and flexural strength of a novel dental
      machinable glass-ceramic (named PMC), and to compare the machinability property
      with that of Vita Mark II and human enamel. METHODS: The raw batch materials were
      selected and mixed. Four groups of novel glass-ceramics were formed at different
      nucleation temperatures, and were assigned to Group 1, Group 2, Group 3 and Group
      4. The machinability of the four groups of novel glass-ceramics, Vita Mark II
      ceramic and freshly extracted human premolars were compared by means of drilling
      depth measurement. A three-point bending test was used to measure the flexural
      strength of the novel glass-ceramics. The crystalline phases of the group with
      the best machinability were identified by X-ray diffraction. RESULTS: In terms of
      the drilling depth, Group 2 of the novel glass-ceramics proves to have the
      largest drilling depth. There was no statistical difference among Group 1, Group
      4 and the natural teeth. The drilling depth of Vita MK II was statistically less
      than that of Group 1, Group 4 and the natural teeth. Group 3 had the least
      drilling depth. In respect of the flexural strength, Group 2 exhibited the
      maximum flexural strength; Group 1 was statistically weaker than Group 2; there
      was no statistical difference between Group 3 and Group 4, and they were the
      weakest materials. XRD of Group 2 ceramic showed that a new type of dental
      machinable glass-ceramic containing calcium-mica had been developed by the
      present study and was named PMC. CONCLUSIONS: PMC is promising for application as
      a dental machinable ceramic due to its good machinability and relatively high
      strength.

PMID- 19604614
TI  - Nationwide survey of resuscitation education in Finland.
AB  - AIMS: Good-quality cardiopulmonary resuscitation (CPR) is highlighted in the
      International Resuscitation Guidelines, but clinically the quality of CPR is
      often poor. Education of CPR has a major role in the primary skills imparted to
      students. Different methods can be used to teach CPR quality. We evaluated the
      current status of their usage in Finland institutes teaching students of
      emergency medicine at different levels. METHODS: The following institutes were
      included in an anonymous survey: medical schools (teaching future physicians),
      universities of applied sciences (paramedics), colleges (emergency medical
      technicians) and emergency services college (fire-fighters). Hours of teaching
      theory lessons of CPR and hours of small group training were evaluated. In
      particular, we focussed on the teaching methods for adequate chest compression
      rate and depth. RESULTS: Twenty-one of 30 institutes responded to the
      questionnaire. The median for hours of theory lessons of CPR was 8h (range: 2-28
      h). The median for hours of small group training was 10 (range: 3-40 h). The
      methods of teaching adequate chest compression rate were instructors' visual
      estimation in 28.5% of the institutions, watch in 33.3%, metronome in 9.5% and
      manikins' graphic in 28.5% of institutions. The methods of teaching adequate
      chest compression depth were instructors' visual estimation in 33.3%, in manikins
      light indicators in 23.8% and manikins' graphics in 52.3% of institutions.
      CONCLUSION: The hours of theoretic lessons and small group training vary widely
      among different institutes. In one-third of institutions, the instructor's visual
      estimation was a sole method used to teach adequate chest compression rate and
      depth. Different technical methods were surprisingly seldom used.

PMID- 19604615
TI  - Basic life support with four different compression/ventilation ratios in a pig
      model: the need for ventilation.
AB  - BACKGROUND: During cardiac arrest the paramount goal of basic life support (BLS)
      is the oxygenation of vital organs. Current recommendations are to combine chest
      compressions with ventilation in a fixed ratio of 30:2; however the optimum
      compression/ventilation ratio is still debatable. In our study we compared four
      different compression/ventilation ratios and documented their effects on the
      return of spontaneous circulation (ROSC), gas exchange, cerebral tissue
      oxygenation and haemodynamics in a pig model. METHODS: Study was performed on 32
      pigs under general anaesthesia with endotracheal intubation. Arterial and central
      venous lines were inserted. For continuous cerebral tissue oxygenation a Licox
      PtiO(2) probe was implanted. After 3 min of cardiac arrest (ventricular
      fibrillation) animals were randomized to a compression/ventilation-ratio 30:2,
      100:5, 100:2 or compressions-only. Subsequently 10 min BLS, Advanced Life Support
      (ALS) was performed (100%O(2), 3 defibrillations, 1mg adrenaline i.v.). Data were
      analyzed with 2-factorial ANOVA. RESULTS: ROSC was achieved in 4/8 (30:2), 5/8
      (100:5), 2/8 (100:2) and 0/8 (compr-only) pigs. During BLS, PaCO(2) increased to
      55 mm Hg (30:2), 68 mm Hg (100:5; p=0.0001), 66 mm Hg (100:2; p=0.002) and 72 mm
      Hg (compr-only; p<0.0001). PaO(2) decreased to 58 mmg (30:2), 40 mm Hg (100:5;
      p=0.15), 43 mm Hg (100:2; p=0.04) and 26 mm Hg (compr-only; p<0.0001). PtiO(2)
      baseline values were 12.7, 12.0, 11.1 and 10.0 mm Hg and decreased to 8.1 mm Hg
      (30:2), 4.1 mm Hg (100:5; p=0.08), 4.3 mm Hg (100:2; p=0.04), and 4.5 mm Hg
      (compr-only; p=0.69). CONCLUSIONS: During BLS, a compression/ventilation-ratio of
      100:5 seems to be equivalent to 30:2, while ratios of 100:2 or compressions-only
      detoriate peripheral arterial oxygenation and reduce the chance for ROSC.

PMID- 19604616
TI  - Survival following cardiac arrest associated with carbon monoxide poisoning.

PMID- 19604617
TI  - Anaphylaxis-Junior doctors' knowledge of guidelines.

PMID- 19604618
TI  - Comparison of efficacy of pulsed biphasic waveform and rectilinear biphasic
      waveform in a short ventricular fibrillation pig model.
AB  - AIM OF STUDY: The waveform designs and their relative defibrillation efficacy of
      external biphasic waveforms may differ remarkably among manufacturers. In this
      study, we compared pulsed biphasic waveform (PBW) with rectilinear biphasic
      waveform (RBW) and their effects on terminating ventricular fibrillation (VF).
      METHODS: VF was electrically induced and untreated for 10s in 6 domestic pigs
      weighing between 56 and 70 kg. The animals were then randomized to attempt
      defibrillation with either a PBW or RBW shock at energy levels of 50-200 J. If
      the delivered shock failed to terminate VF, a 150 J rescue shock was delivered
      with the same waveform. After a recovery interval of 4 min, the sequences were
      repeated for a total of 60 test shocks. The 50% and 80% defibrillation thresholds
      (DFT) were then calculated for the compared waveforms. RESULTS: No differences
      were observed in energy DFT50 and DFT80. Although the peak current and average
      current of the PBW were higher than RBW, there was no change observed in ST
      segment following shocks with both waveforms. CONCLUSION: In the setting of this
      experiment, there was no difference in terms of defibrillation efficacy and
      myocardial injury related to the electrical shocks of the two waveforms.

PMID- 19604619
TI  - Development of a rapid, safe, fiber-optic guided, single-incision cricothyrotomy
      using a large ovine model: a pilot study.
AB  - STUDY AIM: We present a pilot study in which we use an ovine model to develop a
      rapid, safe cricothyrotomy technique using a Melker cuffed 5.0 cricothyrotomy
      catheter loaded over a fiberoptic stainless steel optical stylet. The technique
      requires a single incision. The stylet allows easy placement and facilitates
      visual, tactile, and transillumination confirmation of intratracheal placement.
      We recorded this process on video to facilitate the development of the procedure
      and to allow others to replicate it for further research or refinement. All
      devices used in this technique are currently employed in clinical practice.
      METHODS: We performed the procedure in four anesthetized sheep, varying the
      technique to maximize speed, demonstrate pitfalls, and optimize video recording
      of confirmation methods. We recorded each case using a 4-channel digital video
      recorder. RESULTS: After making a single scalpel incision we inserted the stylet
      and confirmed placement by visualization, transillumination, "click" palpation,
      and gentle stylet-driven tracheal displacement. We passed the cricothyrotomy
      tubes without difficulty and easily ventilated the animals. CONCLUSION: The
      procedure is rapid, incorporates redundant safety features, and uses equipment
      increasingly available to anesthesiologists, emergency physicians, intensivists
      and surgeons. The promising outcome of this pilot study should be verified in a
      larger controlled, comparative trial.

PMID- 19604620
TI  - Prenatal diagnosis of placental teratoma: a case report.

PMID- 19604621
TI  - Examination of the effects of methotrexate on histological and steroid receptor
      changes in the endosalpinx of the rat.
AB  - OBJECTIVES: Methotrexate (MTX) has been a prevalent drug in conservative
      treatment of unruptured tubal pregnancy for many years. However, few researchers
      have performed morphological and protein analysis simultaneously to evaluate the
      specific toxic effects of MTX on the fallopian tubes. The aim of this study was
      to investigate acute and long-term toxic effects of increasing doses of MTX on
      the fallopian tubes and a possible dose-effect relationship. We also discuss the
      potential implications for subsequent pregnancies. STUDY DESIGN: At the 10th day
      and the 2nd and 3rd months after MTX treatment, a total of 108 females SD rats in
      estrus stage (27 rats in each group) were collected according to the dose of MTX
      i.p.: 1, 2, 5mg/kg body weight in groups I, II and III respectively and
      physiological saline i.p. in group IV for control. Nine rats in each group were
      killed at each time point and tissues close to the ampulla of the fallopian tubes
      were dissected for HE staining and routine histological observation. Estrogen
      receptor (ER) and progesterone receptor (PR) expression was detected by
      immunohistochemistry and Western blot. RESULTS: Morphological observation showed
      acute endosalpingitis in group I, becoming more intense with increasing doses of
      MTX in groups II and III in a reversible mode. Expression of ER in the
      endosalpinx significantly decreased in parallel with increasing doses of MTX in a
      dose-effect manner, which was reversible in groups I and II and irreversible in
      group III. Furthermore, ER and PR could recover close to normal levels in groups
      I and II after the 3rd month, while they could not restore to normal in group
      III. CONCLUSIONS: These results provide the first evidence that MTX (>or=5mg/kg)
      can induce long-term, irreversible damage to steroid hormone receptors in the
      fallopian tubes in a dose-dependent manner. We tentatively suggest that MTX
      should be used in a relatively small and safe range of dosage in order to avoid
      impairment and potential risk of subsequent tubal pregnancy or infertility.

PMID- 19604623
TI  - The effect of recycling price uncertainty on municipal waste management choices.
AB  - This paper analyzes the effect of price uncertainty and irreversible investment
      on the decision of municipalities to switch from landfill waste disposal to
      recycling by developing a model to predict recycling adoption behavior and
      applying it to empirical data. It is shown that uncertainty regarding the price
      of recycled materials may induce a risk neutral municipality to prefer landfill
      disposal, even when recycling is less expensive. A model is developed to describe
      the switching process and estimate its parameters using empirical data from 79
      municipalities in Israel. The model is then used to predict municipalities'
      recycling adoption decisions under various assumptions regarding price
      uncertainty. The results support the hypothesis that price uncertainty is a major
      obstacle for recycling. Finally, several options for price stabilization are
      sketched and it is argued that these policies may be effective in establishing
      viable recycling markets.

PMID- 19604622
TI  - Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology.
AB  - Low oxygen availability (hypoxia) is a hallmark of rapidly proliferating tumors
      and has been suggested to be a characteristic of the embryonic and adult stem
      cell niche. The idea of relating cancer to stem cells is increasingly popular due
      to the identification of specific cancer stem cells sharing the typical
      plasticity and motility of pluripotent stem cells. Hypoxia plays a critical role
      in early embryonic development and in tumor progression, participating in
      processes such as angiogenesis, apoptosis, cell migration, invasion and
      metastasis. Some of the molecular pathways that have been shown to mediate these
      hypoxia-induced responses, such as the hypoxia inducible factor (HIF)-1alpha and
      Notch signaling, appear to be active in both embryonic and neoplastic pluripotent
      stem cells. Nevertheless, the mechanisms underlying these regulatory processes
      are not yet fully understood. In this review, we attempt to shed some light on
      the mechanisms involved in hypoxia-dependent processes related to stem cell
      features and tumor progression, such as the maintenance of the undifferentiated
      state, cell proliferation, tumor neovascularization, extra-cellular matrix
      degradation and motility factor up-regulation. With this purpose in mind, we
      summarize recent observations in embryonic, adult and cancer stem cells that
      demonstrate the parallelism existing in their hypoxia responses. Finally, based
      on the observations of our own laboratory and others, we suggest that the
      comparative analysis of the response to low oxygen levels of embryonic stem cells
      and cancer stem cells (such as embryonal carcinoma cells), may throw fresh light
      on our understanding of the mechanisms underlying hypoxia-induced invasiveness
      and the resistance to anticancer treatments, thereby stimulating the development
      of novel therapeutic strategies.

PMID- 19604624
TI  - Leachability of dissolved chromium in asphalt and concrete surfacing materials.
AB  - Leachate metal pollutant concentrations produced from different asphalt and
      concrete pavement surfacing materials were measured under controlled laboratory
      conditions. The results showed that, in general, the concentrations of most metal
      pollutants were below the reporting limits. However, dissolved chromium was
      detected in leachate from concrete (but not asphalt) specimens and more strongly
      in the early-time leachate samples. As the leaching continued, the concentration
      of Cr decreased to below or close to the reporting limit. The source of the
      chromium in concrete pavement was found to be cement. The concentration of total
      Cr produced from leachate of different cement coming from different sources that
      was purchased from retail distributors ranged from 124 to 641mug/L. This result
      indicates that the potential leachability of dissolved Cr from concrete pavement
      materials can be reduced through source control. The results also showed that the
      leachability of dissolved Cr in hardened pavement materials was substantially
      reduced. For example, the concentration of dissolved Cr measured in actual
      highway runoff was found to be much lower than the Cr concentration produced from
      leachate of both open and dense graded concrete pavement specimens under
      controlled laboratory study. It was concluded that pavement materials are not the
      source of pollutants of concern in roadway runoff; rather most pollutants in
      roadway surface runoff are generated from other road-use or land-use sources, or
      from (wet or dry) atmospheric deposition.

PMID- 19604625
TI  - Therapeutic extradural cortical stimulation for Parkinson's Disease: report of
      six cases and review of the literature.
AB  - OBJECTIVES: We report our experience and results with extradural cortical
      stimulation (ECS) in the surgical treatment of Parkinson's Disease (PD). Besides,
      we review the literature supporting the use of this technique. MATERIALS AND
      METHODS: Six patients with advanced PD and exclusion criteria for Deep Brain
      Stimulation (DBS) were included in our ECS protocol. With the aid of functional
      MRI and somato-sensory evoked potentials monitoring, the motor cortex projection
      over the scalp was drawn. Finally, under local anesthesia a stimulation lead was
      placed in the epidural space overlying the central sulcus. RESULTS: Patients
      showed mild daily life activities improvement with a slightly lower levodopa
      equivalent dose, but UPDRS part III scores showed no significant modification.
      CONCLUSIONS: Despite ECS is a minimally invasive surgical technique, our results
      only support its use in selected patients with advanced PD, in whom this therapy
      may be modestly effective. More experimental studies regarding the
      neuromodulation of the basal ganglia-cortex loops are required to optimize its
      clinical application.

PMID- 19604626
TI  - Enhanced cytotoxicity with a novel system combining the paclitaxel-2'
      ethylcarbonate prodrug and an HSV amplicon with an attenuated replication
      competent virus, HF10 as a helper virus.
AB  - We previously demonstrated that HF10, which is a natural, non-engineered HSV-1,
      has potent oncolytic activity in the treatment of solid malignant tumors in vitro
      and in vivo [H. Takakuwa, F. Goshima, N. Nozawa, T. Yoshikawa, H. Kimata, A.
      Nakao, et al., Oncolytic viral therapy using a spontaneously generated herpes
      simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent
      mice, Arch. Virol. 148 (2003) 813-825; S. Kohno, C. Lou, F. Goshima, Y.
      Nishiyama, T. Sata, Y. Ono, Herpes simplex virus type 1 mutant HF10 oncolytic
      viral therapy for bladder cancer, Urology 66 (2005) 1116-1121; D. Watanabe, F.
      Goshima, I. Mori, Y. Tamada, Y. Matsumoto, Y. Nishiyama, Oncolytic virotherapy
      for malignant melanoma with herpes simplex virus type 1 mutant HF10, J. Dermatol.
      Sci. 50 (2008) 185-196; A. Nawa, C. Luo, L. Zhang, Y. Ushijima, D. Ishida, M.
      Kamakura, et al., Non-engineered, naturally oncolytic herpes simplex virus HSV1
      HF10: applications for cancer gene therapy, Curr. Gene. Ther. 8 (2008) 208-221].
      Previous reports have also shown that a combination of HF10 and paclitaxel (TAX)
      was more efficacious than either regimen alone for some types of malignant tumors
      [S. Shimoyama, F. Goshima, O. Teshigahara, H. Kasuya, Y. Kodera, A. Nakao, et
      al., Enhanced efficacy of herpes simplex virus mutant HF10 combined with
      paclitaxel in peritoneal cancer dissemination models, Hepatogastroenterology 54
      (2007) 1038-1042]. In this study, we investigated the efficacy of gene-directed
      enzyme prodrug therapy (GDEPT) using a novel system that combines the paclitaxel
      2'-ethylcarbonate prodrug (TAX-2'-Et) and an HSV amplicon expressing rabbit
      carboxylesterase (CES) with HF10 as a helper virus. This GDEPT system aims to
      produce high level of CES at the tumor site, resulting in efficient local
      conversion of the TAX-2'-Et prodrug into the active drug TAX [A. Nawa, T. Tanino,
      C. Lou, M. Iwaki, H. Kajiyama, K. Shibata, et al., Gene directed enzyme prodrug
      therapy for ovarian cancer: could GDEPT become a promising treatment against
      ovarian cancer?, Anti-Cancer Agents Med Chem 8 (2008) 232-239]. We demonstrated
      that the green fluorescent protein (GFP) gene, as a trace maker, was more
      efficiently introduced by the HSV amplicon compared to the expression vector,
      pHGCX, and that the HSV amplicon system expressed an active CES enzyme that could
      convert TAX-2'-Et to TAX in Cos7 cells. Furthermore, although the cytotoxicity of
      this amplicon system was not enhanced in virus-sensitive tumor cells, it was
      significantly enhanced in low virus-sensitive tumor cells in the presence of the
      prodrug in a concentration-dependent manner, compared to the control virus alone
      (p<0.05). These results indicate that the addition of a prodrug converting enzyme
      may be a feasible approach to further enhance the efficacy of HF10 as a cancer
      therapeutics in low HF10-sensitive malignancies.

PMID- 19604627
TI  - Combination of photocatalysis downstream the non-thermal plasma reactor for
      oxidation of gas-phase toluene.
AB  - Ozone is an undesirable byproduct of non-thermal plasma (NTP) for volatile
      organic compounds (VOCs) control. Photocatalysis combined downstream the NTP
      reactor and ozone was utilized to oxidize toluene. The multiple synergies of
      O(3)/UV/TiO(2) system and the mechanism of toluene decomposition were
      investigated. The influence factors such as energy density, humidity and UV
      sources were also intensively studied. The combination of photocatalysis in the
      post-plasma increased the conversion of toluene and ozone to almost 80 and 90%,
      respectively. Water vapor played a dual role in toluene destruction and ozone
      removal. In total, 0.75% humidity had the best conversion of toluene and ozone at
      these experimental conditions. The conversion of toluene enhanced with increasing
      ozone removal. Among the multiple oxidation processes in the O(3)/UV/TiO(2)
      system, the O(3)/TiO(2) process played a key role in the decomposition of
      toluene.

PMID- 19604628
TI  - Identification of ionic liquid breakdown products in an advanced oxidation
      system.
AB  - Commonly used alkylimidazolium ionic liquids are poorly to negligibly
      biodegradable, and some are toxic, with the potential to poison typical
      biological test systems. Therefore, when ionic liquids are present in
      technological wastewaters they could break through classical wastewater treatment
      systems into natural waters and become potentially persistent pollutants. A
      recent study investigating different advanced oxidation processes found that the
      H(2)O(2)/UV system degraded dissolved imidazolium ionic liquids with the greatest
      efficiency. In the present study, high performance liquid chromatography was
      coupled with electrospray mass spectrometry to separate, analyse and identify
      degradation products following the treatment of ionic liquid solutions with
      H(2)O(2) in the presence of UV irradiation. It was found that hydroxylation in
      short-chain entities occurred mainly within the ring moiety, whereas in the case
      of longer alkylated cations, oxidation of the alkyl chain yielded several
      products. The potential transformation products were identified structurally by
      MS/MS analysis and are discussed in the light of their putative toxicity and
      biodegradability.

PMID- 19604629
TI  - New method for predicting melting points of polynitro arene and polynitro
      heteroarene compounds.
AB  - This work introduces a new method for prediction of melting points of
      nitroaromatic compounds, including polynitro arenes and polynitro heteroarenes,
      through their molecular structures. The new model extends earlier work, which was
      used for carbocyclic nitroaromatic compounds, to estimate melting points of
      heterocyclic aromatic compounds. Some specific functional groups and structural
      parameters can be used to improve the predicted values on the basis of the number
      of carbon, hydrogen and nitrogen atoms. The predicted results show that this
      method gives reliable prediction of melting points with respect to previous work
      and well-developed group additivity methods for different nitroaromatic
      explosives with complex molecular structures.

PMID- 19604630
TI  - Ozone-assisted photocatalytic oxidation of gaseous acetaldehyde on TiO2/H-ZSM-5
      catalysts.
AB  - TiO(2)/H-ZSM-5 catalysts were prepared by impregnation with different amount of
      TiO(2) loading and calcination at various temperatures. The catalysts were
      characterized by X-ray diffraction (XRD), ultraviolet and visible spectroscopy
      (UV-vis) and BET specific surface area. It was demonstrated that the anatase
      TiO(2) retained stable on H-ZSM-5 after heat treatment even at 700 degrees C. The
      activities of samples were investigated under the various conditions of UV, ozone
      and UV-ozone, respectively by the comparison of acetaldehyde degradation. It was
      found that the photocatalysis combined with ozonation promoted the acetaldehyde
      degradation. TiO(2)/H-ZSM-5 catalysts were superior to simple TiO(2) and H-ZSM-5
      with respect to the ozone-assisted photocatalytic oxidation of gaseous
      acetaldehyde, and the activity of the catalyst TiO(2)/H-ZSM-5 (TiO(2):H-ZSM
      5=2:10) is the highest one among all those prepared samples. The improvement was
      attributed to the synergetic effect among adsorption, ozonation and catalytic
      reaction.

PMID- 19604631
TI  - Layer silicates modified with 1,4-bis(3-aminopropyl)piperazine for the removal of
      Th(IV), U(VI) and Eu(III) from aqueous media.
AB  - Natural montmorillonite (M) and synthetic kanemite (K) have been functionalized
      with 1,4-bis(3-aminopropyl)piperazine reacted with methylacrylate to yield new
      inorganic-organic chelating materials. The original and modified materials were
      characterized by X-ray diffractometry, textural analysis, SEM and nuclear
      magnetic nuclei of carbon-13 and silicon-29. The chemically modified clay samples
      (M-APPMA and K-APPMA) showed modification of its physical-chemical properties
      including: specific area 45.0m(2)g(-1) (M) to 978.8 m(2)g(-1) (M-APPMA) and
      23.5m(2)g(-1) (K) to 898.9 m(2)g(-1) (K-APPMA). The ability of these materials to
      remove thorium(IV), uranyl(VI) and europium(III) from aqueous solution was
      followed by a series of adsorption isotherms, which were fitted to non-linear
      Sips adsorption isotherm model. To achieve the best adsorption conditions the
      influence of pH and variation of metal concentration were investigated. The
      energetic effects (Delta(int)H degrees , Delta(int)G degrees and Delta(int)S
      degrees ) caused by metal ions adsorption were determined through calorimetric
      titrations.

PMID- 19604632
TI  - Degradation pathways of crystal violet by Fenton and Fenton-like systems:
      condition optimization and intermediate separation and identification.
AB  - The main advantage of Fenton's reagent (FR) over other OH systems is its
      simplicity. FR has the potential for widespread use in treating wastewater, but
      compared to other OH systems, little information on the dye degradation pathways
      of FR exists. The degradation of crystal violet (CV), a triphenylmethane dye, by
      FR was determined as a function of reagent concentration and ratio and pH in the
      batch treatment. The experimental results showed the optimum Fe(2+)/H(2)O(2)
      ratio to be 0.5mM:50mM and the optimum Fe(3+)/H(2)O(2) ratio to be 1mM:50mM.
      Optimal pH was about 3. To obtain a better understanding of the mechanistic
      details of Fenton reagent's degradation of CV dye, the intermediates of the
      process were separated, identified, and characterized by HPLC-PDA-ESI-MS and GC
      MS techniques in this study. Indications were that the probable degradation
      pathways were N-de-methylation and cleavage of the conjugated chromophore
      structure. The intermediates were generated in the order of the reaction time and
      relative concentration, indicating that the N-de-methylation degradation of CV
      dye is a major reaction pathway. The reaction mechanisms proposed in this
      research should prove useful for future application of the technology to the
      decolorization of dyes.

PMID- 19604633
TI  - Low-cost farmed shrimp shells could remove arsenic from solutions kinetically.
AB  - The purpose of this study was to explore the ability of shrimp shell to remove
      arsenic (As) from aqueous solutions by experimental and modeling analyses. The
      shells of two species of farmed shrimp, black tiger shrimp (Penaeus monodon) and
      white shrimp (Litopenaeus vannamei), were chosen to be the sorbents. The results
      indicate that sorption capacities of black tiger shrimp and white shrimp shells
      were estimated to be 8.1 x 10(-3) to 5.0 x 10(-1) and 7.8 x 10(-3) to 2.4 x 10(
      1)mgg(-1), respectively. Results show that the sorption capacities of the shell
      of black tiger shrimp did not significantly differ from those of white shrimp by
      through analysis of variance ANOVA (F=1.50, n=18, P>0.05). This study found that
      Langmuir and Fruendlich isotherm models described the adsorption processes well
      (r(2)>0.90). The Langmuir-based maximum adsorption capacity was estimated to be
      0.125-0.126 mg g(-1), whereas the Fruendlich-based adsorption capacities ranged
      from 0.105 to 0.124 mg g(-1). Model analysis based on pseudo-second-order
      kinetics reveals that sorption capacity of shrimp shell increases with the
      initial As concentration and retention time in water. Based on isotherm and
      kinetic analyses, the sorption capacity of shell of black tiger shrimp is slight
      higher but insignificant than that of shell of white shrimp for As removal from
      solution. A combination of experiments and modeling suggests that shrimp shell,
      as a waste material, could be utilized potentially for the removal of As from an
      aqueous medium. Although the As-removal capacity of shrimp shell was lower than
      those of natural and chemical sorbents, using shrimp shells as sorbents is less
      expensive and could increase the additional benefit of shrimp products.

PMID- 19604634
TI  - Photocatalytic degradation of diuron in aqueous solution by platinized TiO2.
AB  - The photocatalytic degradation of diuron, which is one of phenylurea herbicides,
      was carried out in the presence of platinized TiO(2) photocatalyst. Platinization
      was found to increase the rate of diuron degradation. When 0.2wt.% of platinum
      was deposited onto the surface of TiO(2), an initial diuron concentration of 10
      mg L(-1) was completely degraded after 20 min. Furthermore, the first-order rate
      constant for diuron degradation by Pt-TiO(2) was ca. 4 times higher than P-25
      TiO(2). In addition, the photocatalytic activity of Pt-TiO(2) was appeared under
      visible light. The decrease of TOC as a result of mineralization of diuron was
      observed during the photocatalytic process. The degree of diuron mineralization
      was about 97% under UV irradiation after 8h. The formations of chloride, nitrate
      and ammonium ions as end-products were observed during the photocatalytic system.
      The decomposition of diuron gave four kinds of intermediate products. The
      degradation mechanism of diuron was proposed on the base of the evidence of the
      identified intermediates. Based on these results, the photocatalytic reaction by
      Pt-TiO(2) could be useful technology for the treatment of wastewater containing
      diuron.

PMID- 19604635
TI  - Study of leaching mechanisms of caesium ions incorporated in Ordinary Portland
      Cement.
AB  - In this work, a study of the leaching kinetics of Cs(+) ions from cement paste
      solids, containing inactive Cs(2)SO(4), is presented, involving (i) the parallel
      performance of leaching experiments at two temperatures (30 degrees C and 70
      degrees C); (ii) the performance of leaching tests with intermediate changes in
      temperature between 30 degrees C and 70 degrees C; (iii) the use of specimens of
      two different thicknesses and (iv) the determination of the distribution of Cs(+)
      in the cement specimen at various stages of the leaching test. The results of
      leaching studies at 30 degrees C with cement solids simulating the composition of
      real radioactive wastes, containing NaNO(3), small amounts of inactive CsNO(3)
      and traces of (137)Cs(+) are also reported. Concentration profiles of Cs(+) in
      inactive specimens showed that part of the Cs(+) (20-30%) tends to be immobilized
      in the matrix, while elution of the readily leachable portion follows Fick's law
      reasonably well. No immobilized Cs(+) was detected in the samples containing
      considerable amounts of NaNO(3). Long-term leaching experiments (up to 8 years)
      revealed acceleration of the elution process (not detectable in short-term
      tests), attributable to increase in porosity caused by erosion of the cement
      matrix. Sorption experiments of Cs(+) ions by cement granules indicated that
      adsorption on cement pore surfaces is not significant. On the other hand, the
      leaching tests at two different temperatures or with intermediate changes in
      temperature between 30 degrees C and 70 degrees C, yielded activation energies
      that indicated a more complicated kinetic behavior.

PMID- 19604636
TI  - Removal of copper and lead from aqueous solution by carboxylic acid
      functionalized deacetylated konjac glucomannan.
AB  - Carboxylic acid functionalized deacetylated konjac glucomannan was synthesized by
      free radical graft copolymerization of methyl acrylate (MA) and methyl
      methacrylate (MMA) onto the backbone of deacetylated konjac glucomannan with
      subsequent chemical activation of the ester groups in the side chains of the
      resulting graft copolymer by sodium hydroxide. Effects of sodium hydroxide
      concentration and hydrolyzed time on the conversion of ester groups into
      carboxylic acid groups were studied. A comprehensive adsorption study of Cu(2+)
      and Pb(2+) ions from aqueous solution was also conducted regarding the effects of
      initial pH, adsorbent dosage, time, and initial concentration. The new konjac
      glucomannan adsorbent offered high removal efficiency, fast adsorption rate and
      high uptake capacity for Cu(2+) and Pb(2+) ions. The maximum removal efficiency
      at pH 5.0 was found to 98% for Cu(2+) and 99% for Pb(2+) ions. The kinetic data
      were fitted well to pseudo-second-order model. The maximum uptake capacity of
      Cu(2+) and Pb(2+) ions onto carboxylic acid functionalized deacetylated konjac
      glucomannan was found to 64.5 mg g(-1) and 191.3 mg g(-1), respectively. The
      isotherm adsorption data was well described by the Langmuir isotherm model.

PMID- 19604637
TI  - Enhancing removal efficiency of anionic dye by combination and calcination of
      clay materials and calcium hydroxide.
AB  - We explored a feasible approach to enhance removal capacity of three natural
      clays for removing anionic dye from aqueous solution. Optimal mixing proportions
      of the clay materials and temperature range for the calcination were
      investigated. We found that the removal efficiency can be improved significantly
      when the clay materials were mixed at certain ratio with the addition of lime and
      the mixed clay materials were calcined 100-300 degrees C. Batch experiments were
      conducted to study the effects of initial concentration, material dosage, contact
      time and pH on dye elimination. Kinetic study showed that more than 80% dye
      removal took place in 5 min. A high removal capacity (>575 mg g(-1)) of the mixed
      clay materials can be achieved at a low adsorbent dose. The mixed clay materials
      can be easily recovered by thermal treatment. The recovered mixtures demonstrated
      an enhanced removal capability after a few cycles of removal and regeneration.
      The results revealed that use of these clay materials could develop a low-cost
      treatment process for industrial wastewater.

PMID- 19604638
TI  - Copper and nitrophenol pollutants removal by Na-montmorillonite/alginate
      microcapsules.
AB  - The use of renewable bioresources allows the development of low cost adsorbents
      that are versatile. In the present paper, the affinity and the removal capacity
      of montmorillonite/alginate microcapsules for a hydrophobic organic pollutant (4
      nitrophenol) and an inorganic pollutant (copper) were evaluated. The
      physicochemical processes through sorption and kinetic experiments under
      different ratios of montmorillonite vs. alginate and initial contaminant
      concentrations were investigated. The total weight loss and diameter decrease
      during the drying process were 90-96% and 64%, respectively. A significant
      decrease in beads diameter, related to water elimination, has been observed
      during the first 24h. Structural modifications that occur during the drying
      process were evaluated using thermal analysis. From correlation coefficients, the
      second-order equation depicts properly the adsorption of copper by the microbeads
      adsorption capacity increases to saturation with time; 3 and 6h were needed to
      reach equilibrium on wet and dry mixed microcapsules. The pseudo-second order
      model properly depicts the adsorption process of 4-NP onto Na-mont and (Na
      mont/SA) mixed microcapsules but failed to reproduce the data observed for the
      alginate beads. Isotherms data were fitted with good correlation using the
      Langmuir model; alginate and montmorillonite adsorption capacities (q(m)/wet
      beads) agree with those obtained by various studies.

PMID- 19604639
TI  - Studies on adsorption of crystal violet dye from aqueous solution onto coniferous
      pinus bark powder (CPBP).
AB  - The present study shows that the coniferous pinus bark powder (CPBP) can be used
      as a potential adsorbent for the removal of crystal violet (basic dye) from
      aqueous solutions. Experiments were carried out as a function of contact time,
      concentration, temperature, pH and dosage. The amount of dye uptake was found to
      vary with increasing initial solution pH and maximum adsorption was observed at
      pH 8. The equilibrium was attained in 2h. The amount of dye uptake (mg/g) was
      found to increase with increase in dye concentration and contact time. The %
      adsorption was found to decrease with increase in amount of adsorbent. The
      thermodynamic parameters were also calculated and the positive value of DeltaH
      degrees indicates the endothermic nature of adsorption. The applicability of the
      three isotherm's model for the present data follows the order:
      Langmuir>Temkin>Freundlich. The kinetics of crystal violet on to the adsorbent
      can be described well by pseudo-second order>Elovich>pseudo-first order equation.

PMID- 19604640
TI  - Distribution and mobility of Cr in tannery waste amended semi-arid soils under
      simulated rainfall.
AB  - This study was conducted to evaluate the distribution and mobility of Cr in
      tannery waste that has been added to semi-arid soils. In addition, the amount of
      total oxidizable soil Cr (III), Cr (VI), pH and soil microbial activities were
      determined. Tannery sludge alone or mixed with fleshing waste was added to two
      types of soils, which were then incubated at 25 degrees C for 6 months and
      subsequently subjected to simulated rainfall. The highest total amount of Cr loss
      occurred due to infiltration, regardless of the treatments. The Cr loss ranged
      from 0.452 to 0.825 microg g(-1) soil for all soils from 1 to 3 months, with the
      exception of those that were located under the canopy and treated with tannery
      sludge and fleshing waste, which had the highest runoff (from 1.312 to 1.667
      microg Crg(-1) soil). The pH of the soil increased from 1 to 3 months (from 7.35
      to 8.46), while the total oxidizable soil Cr (III) (2.12-4.31 mg g(-1) soil)
      peaked after 1 month of treatment. The majority of the fractionated chromium was
      bound to carbonates at initial time, 3 and 6 months prior to and after
      application of the simulated rainfall. The microbial activities decreased in each
      of the treated soils from initial time to 3 months; however, after 6 months
      bacterial activity increased, while pH decreased (from 8.03 to 7.63). Overall,
      these data suggest that pH is responsible for Cr loss in response to infiltration
      and runoff, Cr speciation and the equilibrium of Cr fractionation.

PMID- 19604641
TI  - Continuous electrolytic decarbonation and recovery of a carbonate salt solution
      from a metal-contaminated carbonate solution.
AB  - This work studied the characteristic changes of a continuous electrolytic
      decarbonation and recovery of a carbonate salt solution from a metal-contaminated
      carbonate solution with changes of operational variables in an electrolytic
      system which consisted of a cell-stacked electrolyzer equipped with a cation
      exchange membrane and a gas absorber. The system could completely recover the
      carbonate salt solution from a uranyl carbonato complex solution in a continuous
      operation. The cathodic feed rate could control the carbonate concentration of
      the recovered solution and it affected the most transient pH drop phenomenon of a
      well type within the gas absorber before a steady state was reached, which caused
      the possibility of a CO(2) gas slip from the gas absorber. The pH drop problem
      could be overcome by temporarily increasing the OH(-) concentration of the
      cathodic solution flowing down within the gas absorber only during the time
      required for a steady state to be obtained in the case without the addition of
      outside NaOH. An overshooting peak of the carbonate concentration in the
      recovered solution before a steady state was observed, which was ascribed to the
      decarbonation of the initial solution filled within the stacked cells by a
      redundant current leftover from the complete decarbonation of the feeding
      carbonate solution.

PMID- 19604643
TI  - Advances in TEM orientation microscopy by combination of dark-field conical
      scanning and improved image matching.
AB  - A new approach to automatic TEM-based orientation microscopy is presented, which
      is based on a combination of the techniques of dark-field conical scanning and
      improved image matching, and a diffraction pattern simulation method. For
      indexing, a full experimental diffraction pattern is compared to all possible pre
      calculated diffraction patterns for the given structure by image matching. In
      order to speed up this relatively calculation-intensive algorithm, polar
      transformation and, most important, circular projection that increase the speed
      of pattern indexing by a factor of about 50 are proposed. A microstructure of
      submicron scale and crystallographic orientations in nanocrystalline materials
      are measured successfully. It is proposed that the taken approach of dark-field
      conical scanning and improved image matching may be, in principle, better suited
      for TEM-based orientation microscopy than serial orientation mapping.

PMID- 19604642
TI  - Ketamine produces effective and long-term pain relief in patients with Complex
      Regional Pain Syndrome Type 1.
AB  - Complex Regional Pain Syndrome Type 1 (CRPS-1) responds poorly to standard pain
      treatment. We evaluated if the N-methyl-D-aspartate receptor antagonist S(+)
      ketamine improves pain in CRPS-1 patients. Sixty CRPS-1 patients (48 females)
      with severe pain participated in a double-blind randomized placebo-controlled
      parallel-group trial. Patients were given a 4.2-day intravenous infusion of low
      dose ketamine (n=30) or placebo (n=30) using an individualized stepwise tailoring
      of dosage based on effect (pain relief) and side effects
      (nausea/vomiting/psychomimetic effects). The primary outcome of the study was the
      pain score (numerical rating score: 0-10) during the 12-week study period. The
      median (range) disease duration of the patients was 7.4 (0.1-31.9) years. At the
      end of infusion, the ketamine dose was 22.2+/-2.0 mg/h/70 kg. Pain scores over
      the 12-week study period in patients receiving ketamine were significantly lower
      than those in patients receiving placebo (P<0.001). The lowest pain score was at
      the end of week 1: ketamine 2.68+/-0.51, placebo 5.45+/-0.48. In week 12,
      significance in pain relief between groups was lost (P=0.07). Treatment did not
      cause functional improvement. Patients receiving ketamine more often experienced
      mild to moderate psychomimetic side effects during drug infusion (76% versus 18%,
      P<0.001). In conclusion, in a population of mostly chronic CRPS-1 patients with
      severe pain at baseline, a multiple day ketamine infusion resulted in significant
      pain relief without functional improvement. Treatment with ketamine was safe with
      psychomimetic side effects that were acceptable to most patients.

PMID- 19604644
TI  - Anhedonia and altered cardiac atrial natriuretic peptide following chronic
      stressor and endotoxin treatment in mice.
AB  - Chronic stressors and inflammatory immune activation may contribute to
      pathophysiological alterations associated with both major depression and
      cardiovascular disease. The present study, conducted in mice, assessed whether a
      chronic stressor of moderate severity that induced an anhedonic effect, when
      coupled with a bacterial endotoxin, lipopolysaccharide (LPS), additively or
      interactively provoked circulating and heart atrial natriuretic peptide (ANP), a
      potentially useful diagnostic and prognostic tool in cardiac diseases. As well,
      given the potential role of inflammatory processes in both depression and
      cardiovascular disease, we assessed pro-inflammatory mRNA expression in heart in
      response to the stressor and the LPS treatments. Male CD-1 mice that had been
      exposed to a chronic, variable stressor over 4 weeks displayed reduced sucrose
      consumption, possibly reflecting the anhedonic effects of the stressor. Treatment
      with LPS (10mug) provoked increased circulating corticosterone levels in both
      chronically stressed and non-stressed mice. Moreover, ANP concentrations in
      plasma and in the left ventricle were increased by both the stressor and the LPS
      treatments, as were left atrial and ventricular cytokine (interleukin-1beta;
      tumor necrosis factor-alpha) mRNA expression. Further, these treatments
      synergistically influenced the rise of plasma ANP. A link may exist between
      stressor-provoked depressive features (anhedonia) and immune activation, with
      elevated levels of ANP, a potential marker of cardiovascular disturbance. These
      findings are consistent with the view that chronic stressors and inflammatory
      immune activation may represent a common denominator subserving the frequent
      comorbidity between these illnesses.

PMID- 19604645
TI  - Reprint of "Understanding comorbidity between substance use, anxiety and
      affective disorders: broadening the research base".
AB  - In this paper, we argue that the research base for understanding comorbidity
      between substance use and other mental disorders needs to be broadened. We
      specifically advocate for: 1) more prospective epidemiological studies of
      relationships between alcohol and other drug use disorders and anxiety and mood
      disorders; 2) greater use of twin study designs to disentangle shared genetic and
      environmental contributions to comorbidity; 3) prospective neuroimaging studies
      of the effects of early and sustained alcohol and drug use on the developing
      adolescent brain; 4) a greater focus on the effects on comorbidity of primary and
      secondary prevention interventions for substance use, anxiety, affective and
      conduct disorders among children and adolescents; and 5) better evaluations of
      the impact of treatment upon persons with comorbid substance use and other mental
      disorders.

PMID- 19604646
TI  - Reprint of "Treatment of cannabis use disorders in people with schizophrenia
      spectrum disorders--a systematic review".
AB  - BACKGROUND: Cannabis use disorders (CUD) are prevalent among people with
      schizophrenia spectrum disorders (SSD), with a range of detrimental effects, e.g.
      reduced compliance to medication and psychosocial interventions, and increased
      level of psychotic-dimension symptoms. The aim of this study was to review
      literature on treatments of CUD in SSD-patients. METHODS: PubMed, PsycINFO,
      EMBASE, and The Cochrane Central Register of Controlled Trials were searched.
      RESULTS: 41 articles were selected, 11 treating cannabis as a separate outcome.
      Contingency management was only effective while active. Pharmacological
      interventions appeared effective, but lacked randomized controlled trials (RCTs).
      Psychosocial interventions, e.g. motivational interviewing and cognitive behavior
      therapy (CBT), were ineffective in most studies with cannabis as a separate
      outcome, but effective in studies that grouped cannabis together with other
      substance use disorders. CONCLUSIONS: Insufficient evidence exists on treating
      this form of dual-diagnosis patients. Studies grouping several types of
      substances as a single outcome may overlook differential effects. Future RCTs
      should investigate combinations of psychosocial, pharmacological, and contingency
      management.

PMID- 19604647
TI  - Altered circadian rhythm: possible trigger of familial Mediterranean fever
      attacks.

PMID- 19604648
TI  - Cryptic anhydrobiotic potential in man: implications in medicine.
AB  - Anhydrobiosis ("life without water") is a state of suspended animation in a dry,
      ametabolic condition which some species enter before desiccation stress. This
      state confers resistance to other abiotic stresses such as radiation and heat.
      Once specimens are rehydrated life resumes. Application of such long-term storage
      in dry state without loss of viability would bring a considerable advance in
      organ transplant, maintenance of cell/tissue banks, vaccine storage and transport
      and many other medical applications. Since anhydrobiosis brings biological
      advantage to organisms, one would expect it to be positively selected during
      evolution. Moreover, our still limited understanding of the human genome,
      together with occasional discoveries of hidden endogenous processes, as well as
      reports of suspended animation in higher animals leads us to hypothesize the
      existence of cryptic anhydrobiosis in man. This hypothesis could be tested in
      laboratory animals and human-derived biological samples using several physical
      chemical pre-conditioning/desiccation/rehydration parameters. Finding cryptic
      anhydrobiosis in human tissues would be a breakthrough in medicine providing
      means for long-term storage of biological samples in several stressful
      conditions.

PMID- 19604649
TI  - Unifying electron transfer mechanism for psilocybin and psilocin.

PMID- 19604650
TI  - Sclerosing stromal tumor of the ovary in a 4-year-old girl with characteristics
      of an ovarian signet-ring stromal tumor.
AB  - Ovarian sclerosing stromal tumor (OSST) is an extremely rare neoplasm that
      primarily affects young women. Signet-ring stromal tumor is another rare non
      functioning benign ovarian stromal neoplasm. We report a case of a right OSST
      with prominent characteristics of signet-ring stromal tumor in a 4-year-old girl
      with symptoms of premature thelarche. We describe the clinical,
      histopathological, and immunohistochemical findings and review the literature. To
      our knowledge, the 4-year-old patient presented here is the youngest case of OSST
      reported in premenarchal children. The presence of non-mucin/non-lipid obvious
      signet-ring-like cells in this case suggests a possible relationship between OSST
      and signet-ring stromal tumor of the ovary.

PMID- 19604651
TI  - Response surface methodology: an extensive potential to optimize in vivo
      photodynamic therapy conditions.
AB  - PURPOSE: Photodynamic therapy (PDT) is based on the interaction of a
      photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being
      developed to the in vivo stage, partly because of the difficulty in finding the
      right treatment conditions. Response surface methodology, an empirical modeling
      approach based on data resulting from a set of designed experiments, was
      suggested as a rational solution with which to select in vivo PDT conditions by
      using a new peptide-conjugated PS targeting agent, neuropilin-1. METHODS AND
      MATERIALS: A Doehlert experimental design was selected to model effects and
      interactions of the PS dose, fluence, and fluence rate on the growth of U87 human
      malignant glioma cell xenografts in nude mice, using a fixed drug-light interval.
      All experimental results were computed by Nemrod-W software and Matlab. RESULTS:
      Intrinsic diameter growth rate, a tumor growth parameter independent of the
      initial volume of the tumor, was selected as the response variable and was
      compared to tumor growth delay and relative tumor volumes. With only 13
      experimental conditions tested, an optimal PDT condition was selected (PS agent
      dose, 2.80 mg/kg; fluence, 120 J/cm(2); fluence rate, 85 mW/cm(2)). Treatment of
      glioma-bearing mice with the peptide-conjugated PS agent, followed by the
      optimized PDT condition showed a statistically significant improvement in
      delaying tumor growth compared with animals who received the PDT with the
      nonconjugated PS agent. CONCLUSIONS: Response surface methodology appears to be a
      useful experimental approach for rapid testing of different treatment conditions
      and determination of optimal values of PDT factors for any PS agent.

PMID- 19604652
TI  - Dynamic contrast-enhanced MRI kinetics of invasive breast cancer: a potential
      prognostic marker for radiation therapy.
AB  - PURPOSE: Our goal was to determine the correlations between dynamic contrast
      enhanced MRI (DCE-MRI) kinetics of breast cancers and axillary nodal status (ANS)
      which may have prognostic value in designing radiation therapy recommendations.
      METHODS AND MATERIALS: A retrospective review identified 167 consecutive patients
      treated with external beam radiotherapy for invasive breast cancer from Jan 1,
      2006 to Nov 1, 2007. Patients with DCE-MRI kinetic data from our institution who
      underwent axillary surgical staging prior to chemotherapy were included. ANS was
      assessed as positive or negative by pathology record review. For each primary
      cancer, maximum tumor diameter and kinetic values for initial peak enhancement
      (PE), percent initial rapid enhancement (RE), and percent delayed washout
      enhancement (WE) were measured with a computer-aided evaluation program.
      Univariate, multivariate, and receiver operating characteristic curve analyses
      were performed according to the ANS. RESULTS: Forty-six patients met study
      criteria, with 32 (70%) node-negative and 14 (30%) node-positive patients. Median
      PE was significantly greater in node-positive patients (209%) than in node
      negative patients (138%, p = 0.0027). Similarly, median RE was significantly
      greater in node-positive patients (57%) than in node-negative patients (27%, p =
      0.0436). WE was not different between groups (p = 0.9524). Median maximum tumor
      diameter was greater in node-positive patients (26 mm) than in node-negative
      patients (15 mm, p = 0.015). Multivariate analysis showed that only PE trended
      toward significance (p = 0.18). CONCLUSIONS: DCE-MRI kinetics of primary breast
      cancers correlate with ANS. Multivariate analysis demonstrates the correlation is
      not due simply to underlying lesion size. If validated prospectively, DCE-MRI
      kinetics may aid as a tool in selecting patients or designing fields for
      radiation therapy.

PMID- 19604653
TI  - Differences in clinical results after LINAC-based single-dose radiosurgery versus
      fractionated stereotactic radiotherapy for patients with vestibular schwannomas.
AB  - PURPOSE: To evaluate the outcomes of patients with vestibular schwannoma (VS)
      treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with
      stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This study is based on an
      analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n =
      30). Patients with tumor progression and/or progression of clinical symptoms were
      selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the
      primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor
      progression after neurosurgical intervention. For patients receiving FSRT, a
      median total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x
      1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy
      was prescribed to the 80% isodose. RESULTS: FSRT and SRS were well tolerated.
      Median follow-up time was 75 months. Local control was not statistically
      different for both groups. The probability of maintaining the pretreatment
      hearing level after SRS with doses of < or =13 Gy was comparable to that of FSRT.
      The radiation dose for the SRS group (< or =13 Gy vs. >13 Gy) significantly
      influenced hearing preservation rates (p = 0.03). In the group of patients
      treated with SRS doses of < or =13 Gy, cranial nerve toxicity was comparable to
      that of the FSRT group. CONCLUSIONS: FSRT and SRS are both safe and effective
      alternatives for the treatment of VS. Local control rates are comparable in both
      groups. SRS with doses of < or =13 Gy is a safe alternative to FSRT. While FSRT
      can be applied safely for the treatment of VSs of all sizes, SRS should be
      reserved for smaller lesions.

PMID- 19604654
TI  - Methylenedioxymethamphetamine (MDMA)-related fatalities in Australia:
      demographics, circumstances, toxicology and major organ pathology.
AB  - AIM: To examine the demographic characteristics, circumstances, toxicology and
      major organ pathology of MDMA-related deaths in Australia. METHODS: Retrospective
      review of cases in which MDMA was a cause of death, as identified from the
      National Coronial Information System. RESULTS: 82 cases over a 5-year period were
      identified. The majority of decedents were male (83%), with a median age of 26
      years. Deaths were predominantly due to drug toxicity (82%), with MDMA the sole
      drug causing death in 23% of cases, and combined drug toxicity in 59% of cases.
      The remaining deaths (18%) were primarily due to pathological events/disease or
      injury, with MDMA a significant contributing condition. Cardiovascular pathology,
      typically atherosclerosis, was detected in 58% of decedents, with moderate-severe
      atherosclerosis in 23% of cases. The prevalence of such pathology is higher than
      that expected among similarly aged members of the general population.
      Cerebrovascular pathology, primarily cerebral haemorrhage and hypoxic damage, was
      present in 12% of cases. CONCLUSIONS: MDMA has contributed to a clinically
      significant number of deaths in Australia. The prevalence of cardiovascular
      pathology was similar to that among methamphetamine and cocaine fatalities.
      Whilst cardiovascular pathology may reflect the use of other stimulants, the
      cardiotoxic properties of MDMA have been well-documented. Future studies
      examining MDMA-related morbidity and mortality in the context of other risk
      factors are recommended. Overall, the current study highlights the need to
      educate users about the potential harms of MDMA use, particularly that in
      conjunction with other stimulants, opioids and alcohol, which are known to
      increase overall toxicity.

PMID- 19604655
TI  - Validity of the timeline followback among treatment-seeking smokers in Germany.
AB  - Few studies have assessed the convergent validity of the timeline followback for
      smoking (TLFB-S) among treatment-seeking smokers, and there are no studies
      assessing its discriminant validity. Further, no studies to date have documented
      the psychometric properties of the TLFB in the German population. The aim of this
      study was therefore to test the convergent and discriminant validity of the TLFB
      S among adult, treatment-seeking smokers in Germany. In the context of a smoking
      cessation trial, participants (N=268) completed sociodemographic, TLFB-S and
      other, self-aggregated, single-item (SA) smoking measures at pretreatment. During
      the 12-month posttreatment period, participants completed TLFB-S and
      biochemically validated SA measures of smoking intensity and abstinence at
      regular intervals. Discriminant validity analyses showed no significant
      associations for substance-use and sociodemographic variables and measurement
      discrepancy between TLFB-S and SA measures of pretreatment smoking intensity.
      Convergent validity analyses indicated that TLFB-S and SA measures of smoking
      intensity were in high agreement at both pretreatment and posttreatment. Finally,
      there was high concordance between TLFB-S and SA measures of abstinence at both 1
      and 12-month posttreatment. This study replicated and extended the current
      literature on the TLFB and showed that, even across cultures, it can be a valid
      measure of various smoking-related variables.

PMID- 19604656
TI  - Brucellosis: a re-emerging zoonosis.
AB  - Brucellosis, especially caused by Brucella melitensis, remains one of the most
      common zoonotic diseases worldwide with more than 500,000 human cases reported
      annually. The bacterial pathogen is classified by the CDC as a category (B)
      pathogen that has potential for development as a bio-weapon. Brucella spp. are
      considered as the most common laboratory-acquired pathogens. The geographical
      distribution of brucellosis is constantly changing with new foci emerging or re
      emerging. The disease occurs worldwide in both animals and humans, except in
      those countries where bovine brucellosis has been eradicated. The worldwide
      economic losses due to brucellosis are extensive not only in animal production
      but also in human health. Although a number of successful vaccines are being used
      for immunization of animals, no satisfactory vaccine against human brucellosis is
      available. When the incidence of brucellosis is controlled in the animal
      reservoirs, there is a corresponding and significant decline in the incidence in
      humans.

PMID- 19604657
TI  - Identification of a predominant multilocus sequence type, pulsed-field gel
      electrophoresis cluster, and novel staphylococcal chromosomal cassette in
      clinical isolates of mecA-containing, methicillin-resistant Staphylococcus
      pseudintermedius.
AB  - Methicillin resistance encoded by the mecA gene is increasingly observed in
      Staphylococcus pseudintermedius. Little is known about the population genetics of
      veterinary staphylococci bearing methicillin resistance. The aim of this study
      was to determine the relatedness of resistant bacteria and to compare them with
      methicillin-susceptible isolates. Multilocus sequence typing (MLST) and pulsed
      field gel electrophoresis (PFGE) fragment profiling were performed on methicillin
      resistant S. pseudintermedius (MRSP) and methicillin-susceptible S.
      pseudintermedius (MSSP) isolates obtained from canine samples submitted to the
      veterinary teaching hospital bacteriology service between 2006 and 2008.
      Multilocus sequence typing detected 20 different sequence types, 16 of which were
      not previously described. Methicillin-resistant isolates were predominantly ST
      68, possessed the Staphylococcus aureus-associated staphylococcal chromosomal
      cassette mec (SCCmec) type V(T) and fell within the largest PFGE cluster; whereas
      methicillin-susceptible strains were more genetically diverse. This suggests that
      most methicillin resistance within the population of isolates tested originated
      from a single source which has persisted and expanded for several years.

PMID- 19604658
TI  - Alphaherpesvirus infections in semidomesticated reindeer: a cross-sectional
      serological study.
AB  - Alphaherpesviruses infect a wide range of animal species and cause diseases.
      Cervid herpesvirus 2 (CvHV-2) was originally isolated from reindeer in Finland
      but the impact of CvHV-2 infections on reindeer remains unclear. CvHV-2 infection
      could be partly responsible for calf losses as there are indications that it is
      associated with abortions and neonatal diseases. Previous serosurveys of reindeer
      (Rangifer tarandus tarandus) have shown that an alphaherpesvirus is circulating
      among reindeer in Norway. The aim of the present study was to determine the
      prevalence of CvHV-2 infection among reindeer in various herding districts in
      Finnmark, the largest reindeer area in Norway, and to identify factors associated
      with becoming infected with CvHV-2. A total of 3062 serum samples were tested
      using an ELISA and a sub-set of samples was further tested using a
      seroneutralization test. The ELISA revealed that 49% of samples were positive.
      Extrapolation of the results to the total population (111,350 animals; 66% of the
      Finnmark reindeer population) showed that the seroprevalence in the population
      was 48%. Seroprevalence varied from 7.6% to 90.7% between districts and was
      affected by age, weight and population density. ELISA-positive samples
      neutralized CvHV-2 at serum dilutions greater than those required for
      neutralization of bovine herpesvirus type 1. It is concluded that CvHV-2 is
      endemic throughout the reindeer herding districts of northern Norway.

PMID- 19604659
TI  - A cross-sectional study to collect risk factors associated with stillbirths in
      pig herds.
AB  - The aim of this study was to identify risk factors for stillborn piglets at herd
      level in commercial pig herds. A written questionnaire, containing semi-open
      questions directly or indirectly related to stillborn piglets, was sent to 250
      randomly selected pig herds (>150 sows) in northern Belgium. In total 111/250
      questionnaires were returned (response rate of 44.4%) and 107 were valid for
      analysis. The average reported frequency of stillbirth was 7.5% (S.D. 2.8%). The
      relationship between risk factors and stillbirths was evaluated with a
      generalized linear effects model with the percentage of stillborn piglets as
      outcome variable. Type of breed used on the farm was significantly (P<0.01)
      associated with the percentage of stillborn piglets. A high temperature in the
      farrowing unit (> or =22 degrees C compared to <22 degrees C) was associated with
      significantly (P<0.01) more stillbirths, whereas showering sows with warm water
      before parturition resulted in significantly less stillbirths (5.8%) than no
      showering (7.7%) (P<0.01) and was not significantly different from showering with
      cold water (7.0%) (P=0.26). When supervision of farrowing was performed
      occasionally, significantly more stillbirths (8.1%) were observed in comparison
      with no attending to farrowing (6.5%) (P<0.01) or frequent supervision of
      farrowing (6.9%) (P<0.01). Significant interactions were found between breed and
      showering sows prior parturition or supervision of sows at parturition, and
      between temperature in the farrowing unit at parturition and showering procedure
      of the sows. In conclusion, this study has clearly demonstrated that breed is a
      major factor involved in the frequency of stillbirth. Additionally, some
      management practices before or at parturition may reduce the number of stillborn
      piglets.

PMID- 19604661
TI  - Computer-aided diagnosis in chest radiography: beyond nodules.
AB  - Chest radiographs are the most common exam in radiology. They are essential for
      the management of various diseases associated with high mortality and morbidity
      and display a wide range of findings, many of them subtle. In this survey we
      identify a number of areas beyond pulmonary nodules that could benefit from
      computer-aided detection and diagnosis (CAD) in chest radiography. These include
      interstitial infiltrates, catheter tip detection, size measurements, detection of
      pneumothorax and detection and quantification of emphysema. Recent work in these
      areas is surveyed, but we conclude that the amount of research devoted to these
      topics is modest. Reasons for the slow pace of CAD development in chest
      radiography beyond nodules are discussed.

PMID- 19604660
TI  - Missed opportunities in surveillance and screening systems to detect
      developmental delay: A developing country perspective.
AB  - The future of human societies depends on children being able to achieve their
      optimal physical and psychological development. Developmental delay is failure to
      acquire age-appropriate functionality. It may involve one or more streams of
      development. Responsive parenting has potential to promote better development.
      Primary health physicians are in the best arrangement to provide this assistance
      as they can monitor child's development longitudinally and understand the child's
      developmental trajectory better. Current strategy employed by majority of primary
      care providers to monitor the trajectory is termed 'developmental surveillance'.
      It is "a flexible, continuous process whereby knowledgeable professionals perform
      skilled observations of children during the provision of health care". Age
      appropriate developmental checklists are also used to record milestones as part
      of surveillance. Both, the American Academy of Pediatrics and the British Joint
      Working Party on Child Health Services, recommend developmental surveillance by
      physicians as a method of identification of developmental delays. Developmental
      screening, however, improves the accuracy of identifying children with delay,
      compared with surveillance. Primary health physicians should consider using
      developmental screening tools that are standardized, reliable, valid and
      practical in the office setting, be familiar with screening techniques which
      should be incorporated into ongoing care, and keep abreast of current literature.
      Pakistan, as a developing country, needs specific strategies to ensure that we
      seize all the chances to detect this delay at an earlier age and introduce
      intervention, in order to lessen the burden of the disability on child, family
      and society.

PMID- 19604663
TI  - Is it good to express uncertainty to a patient? Correlates and consequences for
      medical students in a standardized patient visit.
AB  - OBJECTIVE: To examine the consequences of expressions of uncertainty (EOUs) in
      medical student interactions, with a particular focus on the gender of the
      expressor. METHODS: EOUs were identified in 147 videotaped interactions between
      third-year medical students and standardized patients enacting four medical
      scenarios. The encounters were also analyzed using the Roter Interaction Analysis
      System (RIAS). A subset of these interactions was shown to 244 analogue patients
      who rated satisfaction, liking, and perceived competence and confidence. RESULTS:
      Female medical students used more EOUs but not when adjusted for total number of
      statements. The EOU rate varied across scenarios. A higher EOU rate was perceived
      as more affectively negative by both RIAS trained coders and analogue patients.
      EOU rate was inversely related to analogue patient satisfaction and liking and
      this relationship was stronger for males than females. Female student use of EOUs
      was more strongly associated with ratings of anxiety than was male EOU use.
      CONCLUSION: There was an overall negative perception of medical students who
      expressed uncertainty; however, the strength of the associations varied due to
      medical student gender. PRACTICE IMPLICATIONS: The implications for medical
      education are discussed.

PMID- 19604662
TI  - Evaluation of portosystemic collaterals by MDCT-MPR imaging for management of
      hemorrhagic esophageal varices.
AB  - OBJECTIVE: To study the correlation between changes in portosystemic collaterals,
      evaluated by multidetector-row computed tomography imaging using multiplanar
      reconstruction (MDCT-MPR), and prognosis in patients with hemorrhagic esophageal
      varices (EV) after endoscopic treatment. METHODS: Forty-nine patients with
      primary hemostasis for variceal bleeding received radical endoscopic treatment:
      endoscopic injection sclerotherapy (EIS) or endoscopic variceal ligation (EVL).
      Patients were classified according to the rate of reduction in feeding vessel
      diameter on MDCT-MPR images, into the narrowing (n=24) and no-change (n=25)
      groups. We evaluated changes in portosystemic collaterals by MDCT-MPR before and
      after treatment, and determined rebleeding and survival rates. RESULTS: The left
      gastric and paraesophageal (PEV) veins were recognized as portosystemic
      collaterals in 100 and 80%, respectively, of patients with EV on MDCT-MPR images.
      The rebleeding rates at 1, 2, 3, and 5 years after endoscopic treatment were 10,
      15, 23, and 23%, respectively, for the narrowing group, and 17, 24, 35, and 67%,
      respectively, for the no-change group (P=0.068). Among no-change group, the
      rebleeding rate in patients with large PEV was significantly lower than that with
      small PEV (P=0.027). The rebleeding rate in patients with small PEV of the no
      change group was significantly higher than that in the narrowing group (P=0.018).
      There was no significant difference in rebleeding rates between the no-change
      group with a large PEV and narrowing group (P=0.435). CONCLUSION: Changes in
      portosystemic collaterals evaluated by MDCT-MPR imaging correlate with rebleeding
      rate. Evaluation of portosystemic collaterals in this manner would provide useful
      information for the management of hemorrhagic EV.

PMID- 19604664
TI  - Failure of closed reduction after dislocation of Austin Moore hemiarthroplasty:
      an analysis of risk factors a 6-year follow-up study.
AB  - The aim of this study was to determine the factors associated with failure of
      closed reduction of dislocated Austin Moore hemiarthroplasty for subcapital neck
      of femur fracture. There were 44 (1.8%) cases of dislocation for a 6-year period.
      There were 28 females and 12 males, and mean age was 85.6 years. Thirty-two
      patients (80%) had redislocations, and 13 patients (40%) required 2 or more
      closed reductions. Twenty-eight patients subsequently had a Girdlestone
      arthroplasty. Dementia and a previous failed closed reduction were associated
      with a higher failure rate (P = .03 and .04, respectively). Failed close
      reduction patients also had a higher 6-month mortality rate (P = .04). Closed
      reduction after Austin Moore hip dislocation has a higher failure rate
      significantly in patients with dementia and are associated with a higher
      mortality rate. We believe closed reduction should be avoided in these groups of
      patients, and Girdlestone procedure was considered after initial first
      dislocation.

PMID- 19604665
TI  - Morbidly obese, diabetic, younger, and unilateral joint arthroplasty patients
      have elevated total joint arthroplasty infection rates.
AB  - The study aims to delineate the deep infection rates and infection risk factors
      for primary total knee and total hip arthroplasty patients. A retrospective
      review was conducted on 6108 patients from 1991 to 2004. The deep infection cases
      were compared to the noninfected cohort whereby infection risk factors were
      identified. Of the 8494 joint arthroplasties, 43 (0.51%) developed a deep
      infection (30 total knee arthroplasties, 13 total hip arthroplasties). Patients
      with a body mass index greater than 50 had an increased odds ratio of infection
      of 21.3 (P < .0001). Diabetic patients were 3 times as likely to become infected
      compared to nondiabetic patients (P = .0027). Simultaneous bilateral total joint
      arthroplasties were found to have developed infection 3 times less frequently
      than those performed as unilateral procedures (P = .0024). The average age in our
      infection cohort was 64.3 and 68.4 in the noninfected cohort. In this
      retrospective review study, obesity, diabetes, and younger age were found to be
      risk factors for joint arthroplasty infection.

PMID- 19604666
TI  - Rates and predictors of remission in young women with specific phobia: a
      prospective community study.
AB  - This prospective study reports rates and predictors of remission in young women
      with specific phobia. Data came from a prospective community study, in which
      German women (aged 18-25 years) completed an extended version of the Anxiety
      Disorders Interview Schedule (ADIS-IV-L) at two time points. Of the 137 women
      with specific phobia at baseline, 41.6% were partially remitted and an additional
      19.0% were fully remitted at follow-up, defined as absence of any specific fears.
      A remitting course of specific phobia was predicted by residual protective
      factors at baseline, especially participants' positive mental health and life
      satisfaction. Baseline levels of stress, coping skills, cognitive factors,
      psychopathology, and specific phobia characteristics did not predict remission.
      Results show that specific phobia in young women rarely takes a stable course at
      the full diagnostic threshold. The factors that influence remission of specific
      phobia are different from those that predict the incidence.

PMID- 19604667
TI  - Dysfunctional cognitive appraisal and psychophysiological reactivity in acute
      stress disorder.
AB  - The present study investigated the extent of dysfunctional appraisal as measured
      with the Posttraumatic Cognitions Inventory (PTCI) and physiological responses to
      trauma-related material in patients with acute stress disorder (ASD; N=44) in
      comparison to participants without trauma exposure (N=27). Heart-rate (HR), skin
      conductance responses (SCR), and viewing time were recorded in response to - for
      trauma victims - idiosyncratically trauma-relevant and control pictures. ASD
      patients evidenced greater dysfunctional appraisal than control participants with
      regard to the PTCI scales Self and World and also an accelerative HR reaction and
      greater SCRs to trauma-relevant pictures. Among patients, PTCI was highly
      correlated with ASD severity while PTCI World was positively correlated with
      resting HR and depression. Amplitude of the HR reaction to trauma-related
      pictures was negatively correlated with viewing time. Results suggest that
      dysfunctional appraisal and autonomic reactivity are only loosely related in ASD.

PMID- 19604668
TI  - Intellectual disability and its relationship to autism spectrum disorders.
AB  - Intellectual disability (ID) and autism spectrum disorders (ASDs) covary at very
      high rates. Similarly, greater severity of one of these two disorders appears to
      have effects on the other disorder on a host of factors. A good deal of research
      has appeared on the topic with respect to nosology, prevalence, adaptive
      functioning, challenging behaviors, and comorbid psychopathology. The purpose of
      this paper was to provide a critical review and status report on the research
      published on these topics. Current status and future directions for better
      understanding these two covarying disorders was reviewed along with a discussion
      of relevant strengths and weaknesses of the current body of research.

PMID- 19604669
TI  - A new bidirectional heteroassociative memory encompassing correlational,
      competitive and topological properties.
AB  - In this paper, we present a new recurrent bidirectional model that encompasses
      correlational, competitive and topological model properties. The simultaneous use
      of many classes of network behaviors allows for the unsupervised
      learning/categorization of perceptual patterns (through input compression) and
      the concurrent encoding of proximities in a multidimensional space. All of these
      operations are achieved within a common learning operation, and using a single
      set of defining properties. It is shown that the model can learn categories by
      developing prototype representations strictly from exposition to specific
      exemplars. Moreover, because the model is recurrent, it can reconstruct perfect
      outputs from incomplete and noisy patterns. Empirical exploration of the model's
      properties and performance shows that its ability for adequate clustering stems
      from: (1) properly distributing connection weights, and (2) producing a weight
      space with a low dispersion level (or higher density). In addition, since the
      model uses a sparse representation (k-winners), the size of topological
      neighborhood can be fixed, and no longer requires a decrease through time as was
      the case with classic self-organizing feature maps. Since the model's learning
      and transmission parameters are independent from learning trials, the model can
      develop stable fixed points in a constrained topological architecture, while
      being flexible enough to learn novel patterns.

PMID- 19604670
TI  - Distance coding strategies based on the entorhinal grid cell system.
AB  - Estimating and keeping track of the distance from salient points of the
      environment are important constituents of the spatial awareness and navigation.
      In rodents, the majority of principal cells in the hippocampus are known to be
      correlated with the position of the animal. However, the lack of topography in
      the hippocampal cognitive map does not support the assumption that connections
      between these cells are able to store and recall distances between coded
      positions. In contrast, the firing fields of the grid cells in the medial
      entorhinal cortex form triangular grids and are organized on metrical principles.
      We suggest a model in which a hypothesized 'distance cell' population is able to
      extract metrics from the activity of grid cells. We show that storing the
      momentary activity pattern of the grid cell system in a freely chosen position by
      one-shot learning and comparing it to the actual grid activity at other positions
      results in a distance dependent activity of these cells. The actual distance of
      the animal from the origin can be decoded directly by selecting the distance cell
      receiving the largest excitation or indirectly via transmission of local
      interneurons. We found that direct decoding works up to the longest grid spacing,
      but fails on smaller scales, while the indirect way provides precise distance
      determination up to the half of the longest grid spacing. In both cases,
      simulated distance cells have a multi-peaked, patchy spatial activity pattern
      consistent with the experimentally observed behavior of granule cells in the
      dentate gyrus.

PMID- 19604671
TI  - Sparse kernel learning with LASSO and Bayesian inference algorithm.
AB  - Kernelized LASSO (Least Absolute Selection and Shrinkage Operator) has been
      investigated in two separate recent papers [Gao, J., Antolovich, M., & Kwan, P.
      H. (2008). L1 LASSO and its Bayesian inference. In W. Wobcke, & M. Zhang (Eds.),
      Lecture notes in computer science: Vol. 5360 (pp. 318-324); Wang, G., Yeung, D.
      Y., & Lochovsky, F. (2007). The kernel path in kernelized LASSO. In International
      conference on artificial intelligence and statistics (pp. 580-587). San Juan,
      Puerto Rico: MIT Press]. This paper is concerned with learning kernels under the
      LASSO formulation via adopting a generative Bayesian learning and inference
      approach. A new robust learning algorithm is proposed which produces a sparse
      kernel model with the capability of learning regularized parameters and kernel
      hyperparameters. A comparison with state-of-the-art methods for constructing
      sparse regression models such as the relevance vector machine (RVM) and the local
      regularization assisted orthogonal least squares regression (LROLS) is given. The
      new algorithm is also demonstrated to possess considerable computational
      advantages.

PMID- 19604672
TI  - Neural networks with multiple general neuron models: a hybrid computational
      intelligence approach using Genetic Programming.
AB  - Classical neural networks are composed of neurons whose nature is determined by a
      certain function (the neuron model), usually pre-specified. In this paper, a type
      of neural network (NN-GP) is presented in which: (i) each neuron may have its own
      neuron model in the form of a general function, (ii) any layout (i.e network
      interconnection) is possible, and (iii) no bias nodes or weights are associated
      to the connections, neurons or layers. The general functions associated to a
      neuron are learned by searching a function space. They are not provided a priori,
      but are rather built as part of an Evolutionary Computation process based on
      Genetic Programming. The resulting network solutions are evaluated based on a
      fitness measure, which may, for example, be based on classification or regression
      errors. Two real-world examples are presented to illustrate the promising
      behaviour on classification problems via construction of a low-dimensional
      representation of a high-dimensional parameter space associated to the set of all
      network solutions.

PMID- 19604673
TI  - Evaluation of atmospheric Poaceae pollen concentration using a neural network
      applied to a coastal Atlantic climate region.
AB  - In the South of Europe an important percentage of population suffers pollen
      allergies, being the Poaceae pollen the major source. One of aerobiology's
      objectives is to develop statistical models enabling the short- and long-term
      prediction of atmospheric pollen concentrations to take preventative measures to
      protect allergic patients from the severity of the atmospheric pollen season. The
      implementation of a computational model based on supervised MLP neural network
      was applied for the prediction of the atmospheric Poaceae pollen concentration.
      There is a good correlation between the values predicted by the ANN for the
      training cases in comparison with the real pollen concentrations. A high
      coefficient of linear regression (R(2)) of 0.9696 was obtained. The accuracy of
      the neural network developed was tested with data from 2006 and 2007, which was
      not taken into account to establish the aforementioned models. Neural networks
      provided us a good tool to forecasting allergenic airborne pollen concentration
      helping the automation of the prediction system in the aerobiological information
      diffusion to the population suffering from allergic problems.

PMID- 19604674
TI  - Associative memories based on continuous-time cellular neural networks designed
      using space-invariant cloning templates.
AB  - Associative memories are brain-style devices designed to store a set of patterns
      as stable equilibria such that the stored patterns can be reliably retrieved with
      the initial probes containing sufficient information about the patterns. This
      paper presents a new design procedure for synthesizing associative memories based
      on continuous-time cellular neural networks with time delays characterized by
      input and output matrices obtained using two-dimensional space-invariant cloning
      templates. The design procedure enables hetero-associative or auto-associative
      memories to be synthesized by solving a set of linear inequalities with few
      design parameters and retrieval probes feeding from external inputs instead of
      initial states. The designed associative memories are robust in terms of design
      parameter selection. In addition, the hosting cellular neural networks are
      guaranteed to be globally exponentially stable. Simulation and experimental
      results of illustrative examples and Monte Carlo tests demonstrate the
      applicability and superiority of the methodology.

PMID- 19604675
TI  - Transnasal endoscopic marsupialization of bilateral nasoalveolar cysts.
AB  - Nasoalveolar cysts are uncommon nonodontogenic and developmental cysts with an
      uncertain pathogenesis. This cyst has been reported to occur bilaterally in 10
      11% of cases. This case report describes a 45-year-old woman in whom the
      clinicopathologic findings were consistent with bilateral nasoalveolar cysts. The
      authors report a new, less invasive method for transnasal endoscopic
      marsupialization of bilateral nasoalveolar cysts. Transnasal endoscopic
      marsupialization has benefits for the treatment of bilateral and unilateral
      nasoalveolar cysts.

PMID- 19604676
TI  - Leukotriene B4-loaded microspheres as a new approach to enhance antimicrobial
      responses in Histoplasma capsulatum-infected mice.
AB  - Histoplasmosis is a pulmonary disease characterised by chronic granulomatous and
      suppurative inflammatory reactions caused by Histoplasma capsulatum. Regarding
      new therapies to control fungal infections, the aim of this study was to
      investigate whether pulmonary administration of leukotriene B(4) (LTB(4))-loaded
      microspheres (MS) could confer protection to 5-lipoxygenase knockout (5-LO(-/-))
      mice infected by H. capsulatum. In this study, MS containing LTB(4) were
      administered intranasally to mice infected by H. capsulatum. On Day 14 after the
      infection, fungal recovery from the lungs and histology were evaluated and
      inflammatory cytokines were measured. Pulmonary administration of LTB(4)-loaded
      MS was able to reduce fungal recovery from infected lungs. Production of
      important inflammatory cytokines related to host defence was augmented following
      MS administration to the lungs. Lung histology also showed that infected mice
      presented a clear reduction in the fungal burden following the pulmonary release
      of LTB(4) from MS. Our study provides evidence that the proposed biodegradable
      microparticulate system, which can release LTB(4) to the lungs, can be employed
      as therapy, enhancing the antimicrobial activity of host cells during
      histoplasmosis.

PMID- 19604677
TI  - Differential influence of selective 5-HT5A vs 5-HT1A, 5-HT1B, or 5-HT2C receptor
      blockade upon light-induced phase shifts in circadian activity rhythms:
      interaction studies with citalopram.
AB  - Though serotonergic mechanisms modulate circadian rhythms, roles of individual
      serotonin (5-HT) receptors remain uncertain since data are lacking for
      antagonists. Herein, both the 5-HT(5A) receptor antagonist, A843277 (10 mg/kg),
      and the 5-HT(1B) antagonist, SB224289 (1 mg/kg), inhibited light-induced phase
      advances in hamster circadian wheel-running rhythms. Conversely, though 5-HT(1A)
      and 5-HT(7) receptors are likewise implicated in circadian scheduling, their
      blockade by WAY100635 (0.5 mg/kg) and SB269970 (1 mg/kg), respectively, was
      ineffective. Since actions of 5-HT reuptake inhibitors are modified by
      antagonists, we evaluated their influence on suppression of phase advances by
      citalopram (10 mg/kg). Its action was potentiated by WAY100635 and the 5-HT(2C)
      antagonist, SB242084 (1 mg/kg), but not by A842377, SB224289, SB269970, and
      antagonists at 5-HT(2A) (MDL100907) and 5-HT(6) (SB399885) receptors. In
      conclusion, this is the first in vivo evidence for an influence of 5-HT(5A)
      receptors upon circadian rhythms, but no single class of 5-HT receptor mediates
      their control by citalopram.

PMID- 19604679
TI  - [The first consultation with an adolescent].
AB  - It is crucial not to miss the first consultation with an adolescent. This article
      reviews some of the essential step necessary to help make the first consultation
      a success: the time to devote to the patient, the preparation of the
      consultation, mandatory issues to address, clinical/physical examination,
      conclusion of the consultation, the prescriptions and the follow-up.

PMID- 19604680
TI  - Global recognition of qualified toxicologic pathologists: credential review as a
      potential route for recognizing the proficiency of pathologists involved in
      regulatory-type nonclinical studies.
AB  - Recent international summits of the International Federation of Societies of
      Toxicologic Pathologists (IFSTP) have debated the desirability and potential
      means by which the proficiency of an individual toxicologic pathologist might be
      recognized and communicated throughout the world. The present document describes
      the advantages and disadvantages of implementing such a global recognition system
      by any means, and provides a proposal whereby recognition might be accorded via
      rigorous credential review of a practitioner's education and experience.

PMID- 19604681
TI  - Workshop proceedings: DHA as a required nutrient.

PMID- 19604682
TI  - Canola straw as a bio-waste resource for medium density fiberboard (MDF)
      manufacture.
AB  - Canola straw as an agricultural residue has been investigated for MDF production.
      The variables were steaming time (2, 5 and 8 min), the resin content (9% and
      11%), and press time (4 and 6 min). Common physical and mechanical properties of
      experimental boards including modulus of rupture (MOR), modulus of elasticity
      (MOE), internal bond strength (IB) and thickness swelling (TS) were measured.
      Fiber properties of canola straw including length, diameter and cell wall
      thickness were determined. The results showed that all the tested mechanical
      properties improved with the increase of steaming time level. The results were
      close to the minimum requirements of MDF specified in the ANSI A208.2 standard.
      Dimensional stability of the MDFs improved as adhesive content increased. The IB
      values are positively affected by the increase of press time. MDF properties made
      from canola straw possess acceptable qualities as compared to those made from
      other non-wood plants. Furthermore, the fiber dimensions of canola straw were
      also in the range of reported values in hardwoods.

PMID- 19604684
TI  - Development. Editorial overview.

PMID- 19604683
TI  - Building the world's best hearing aid; regulation of cell fate in the cochlea.
AB  - In mammals, auditory perception is initially mediated through sensory cells
      located in a rigorously patterned mosaic of unique cell types located within the
      coiled cochlea. Identification of the factors that direct multipotent progenitor
      cells to develop as each of these specialized cell types has the potential to
      enhance our understanding of the development of the auditory system and to
      identify potential targets for regenerative therapies. Recent results have
      identified specific signaling molecules and pathways, including Notch, Hedgehog,
      Sox2 and Fgfs, that guide progenitor cells to develop first as a sensory
      precursor, referred to as a prosensory cell, and subsequently as one of the
      specialized cell types within the sensory mosaic.

PMID- 19604685
TI  - Tar reduction in pyrolysis vapours from biomass over a hot char bed.
AB  - The behaviour of pyrolysis vapours over char was investigated in order to
      maximise tar conversion for the development of a new fixed bed gasifier. Wood
      samples were decomposed at a typical pyrolysis temperature (500 degrees C) and
      the pyrolysis vapours were then passed directly through a tar cracking zone in a
      tubular reactor. The product yields and properties of the condensable phases and
      non-condensable gases were studied for different bed lengths of char (0-450 mm),
      temperatures (500-800 degrees C), particle sizes (10 and 15 mm) and nitrogen
      purge rates (1.84-14.70 mm/s). The carbon in the condensable phases showed about
      66% reduction by a 300 mm long char section at 800 degrees C, compared to that
      for pyrolysis at 500 degrees C. The amount of heavy condensable phase decreased
      with increasing temperature from about 18.4 wt% of the biomass input at 500
      degrees C to 8.0 wt% at 800 degrees C, forming CO, H(2) and other light
      molecules. The main mode of tar conversion was found to be in the vapour phase
      when compared to the results without the presence of char. The composition of the
      heavy condensable phase was simplified into much fewer secondary and tertiary tar
      components at 800 degrees C. Additional measures were required to maximise the
      heterogeneous effect of char for tar reduction.

PMID- 19604686
TI  - Validity of Monod kinetics at different sludge ages--peptone biodegradation under
      aerobic conditions.
AB  - The study presented an evaluation of the effect of culture history (sludge age)
      on the growth kinetics of a mixed culture grown under aerobic conditions. It
      involved an experimental setup where a lab-scale sequencing batch reactor was
      operated at steady-state at two different sludge ages (theta(X)) of 2 and 10
      days. The system sustained a mixed culture fed with a synthetic substrate mainly
      consisting of peptone. The initial concentration of substrate COD was selected
      around 500 mg COD/L. Polyhydroxyalkanoate (PHA) storage occurred to a limited
      extent, around 30 mg COD/L for theta(X)=10 days and 15 mg COD/L for theta(X)=2
      days. Evaluation of the experimental data based on calibration of two different
      models provided consistent and reliable evidence for a variable Monod kinetics
      where the maximum specific growth rate, was assessed as 6.1/day for theta(X)=2
      days and 4.1/day for theta(X)=10 days. A similar variability was also applicable
      for the hydrolysis and storage kinetics. The rate of storage was significantly
      lower than the levels reported in the literature, exhibiting the ability of the
      microorganisms to regulate their metabolic mechanisms for adjusting the rate of
      microbial growth and storage competing for the same substrate. This adjustment
      evidently resulted in case-specific, variable kinetics both for microbial growth
      and substrate storage.

PMID- 19604687
TI  - Enzymatic hydrolysis of cellulosic municipal wastewater treatment process
      residuals as feedstocks for the recovery of simple sugars.
AB  - This study examined the hydrolysis of lignocellulose extracted from municipal
      wastewater treatment process residuals for the purpose of investigating low-cost
      feedstocks for ethanol production, while providing an alternative solid waste
      management strategy. Primary and thickened waste activated sludges and
      anaerobically digested biosolids underwent various pre-treatments to enhance
      subsequent enzymatic hydrolysis. Half of the pre-treated samples were dried and
      grinded, while the other half were used as is (wet). The wet primary sludge
      yielded the highest reducing sugar conversions. When wet primary sludge without
      pre-treatment was hydrolyzed at 40 degrees C and an enzyme loading of 800 U/g
      substrate, 31.1+/-2.7% was converted to reducing sugars in 24 h. This increased
      to 54.2+/-4.0% when HCl and KOH pre-treatments were applied. FTIR analyses were
      used to examine differences in the sludge compositions. These indicated that the
      cellulose content in the primary sludge was higher than that of the thickened
      waste activated sludge and biosolids, which was consistent with the higher
      reducing sugar yields observed in the primary sludge.

PMID- 19604688
TI  - A novel UASB-MFC-BAF integrated system for high strength molasses wastewater
      treatment and bioelectricity generation.
AB  - An up-flow anaerobic sludge blanket reactor-microbial fuel cell-biological
      aerated filter (UASB-MFC-BAF) system was developed for simultaneous
      bioelectricity generation and molasses wastewater treatment in this study. The
      maximum power density of 1410.2 mW/m(2) was obtained with a current density of
      4947.9 mA/m(2) when the high strength molasses wastewater with chemical oxygen
      demand (COD) of 127,500 mg/l was employed as the influent. The total COD, sulfate
      and color removal efficiencies of the proposed system were achieved of 53.2%,
      52.7% and 41.1%, respectively. Each unit of this system had respective function
      and performed well when integrated together. The UASB reactor unit was mainly
      responsible for COD removal and sulfate reduction, while the MFC unit was used
      for the oxidation of generated sulfide with electricity generation. The BAF unit
      dominated color removal and phenol derivatives degradation. This study is a
      beneficial attempt to combine MFC technology with conventional anaerobic-aerobic
      processes for actual wastewater treatment.

PMID- 19604689
TI  - Composition of organic matter in particle size fractionated pig slurry.
AB  - Pig slurry is a heterogeneous mixture of different particle sizes that will have
      different mobility in soil. Therefore, a physically fractionated pig slurry
      sample was analysed, e.g. using pyrolysis-field ionisation mass spectrometry (Py
      FIMS) in an effort to identify relationships between particle size and
      composition of organic matter. The presumably most mobile fractions in soils (<63
      microm) accounted for approximately 50% of slurry dry matter and were dominated
      by lignins, and N-containing compounds. Sterols were especially abundant in the
      larger-sized fractions, which corresponds to their reported distribution in soils
      and surface waters. The averaged molecular masses indicated similarities of
      fractions <10 microm to aquatic humic substances and increasing content of plant
      material with increasing particle size. A statistical analysis of the compound
      class distribution revealed that the analysis of three particle size fractions is
      essential for the assessment of the composition and properties of slurry
      constituents.

PMID- 19604690
TI  - Modelling of parameters for optimization of maturity in composting trimming
      residues.
AB  - In this paper, changes in physico-chemical parameters during trimmings residue
      composting (cation exchange capacity, germination index, self-heated, NH(4)/NO(3)
      ratio and C(FA)/C(HA) ratio) in relation to environmental composting parameters
      (time, aeration, moisture and particle size) of the composting process were
      studied. A central composite experimental design was used to obtain the
      polynomial model for each dependent variable. Results of the modelling showed
      that among the studied range, moisture was the highest influenced parameter in
      maturity evaluation, with respect to aeration and particle size. An exception was
      found for CEC evolution. In this parameter, the highest influence was found for
      particle size. Moreover, a product with acceptable chemical properties entails
      operating at medium moisture content (55%) and medium-to-high particle size (3-5
      cm). Moderate to low aeration (0.2 m(3) air kg(-1) d(-1)) would be the best
      compromise to composting this residue, due to the scarce statistical influence of
      this independent variable.

PMID- 19604691
TI  - Removal of water turbidity by natural coagulants obtained from chestnut and
      acorn.
AB  - The ability of seed extracts of several species of chestnut and acorn to act as
      natural coagulants was tested using a synthetic turbid water. Active components
      were extracted from ground seeds of Horse chestnut and acorns of some species of
      family Fagaceae: Common oak, Turkey oak, Northern red oak and European chestnut.
      All investigated extracts had coagulation capabilities and their amounts depended
      on pH values and initial turbidities. The seed extracts from European chestnut
      and Common oak acorn were the most efficient expressing the highest coagulation
      activities, about 80% and 70%, respectively, in both low and medium investigated
      water turbidities at the lowest coagulant dose 0.5 ml/L.

PMID- 19604692
TI  - Biohydrogen production from cellulosic hydrolysate produced via temperature-shift
      enhanced bacterial cellulose hydrolysis.
AB  - A "temperature-shift" strategy was developed to improve reducing sugar production
      from bacterial hydrolysis of cellulosic materials. In this strategy, production
      of cellulolytic enzymes with Cellulomonas uda E3-01 was promoted at a preferable
      temperature (35 degrees C), while more efficient enzymatic cellulose hydrolysis
      was achieved under an elevated culture temperature (45 degrees C), at which cell
      growth was inhibited to avoid consumption of reducing sugar. This temperature
      shift strategy was shown to markedly increase the reducing sugar (especially,
      monosaccharide and disaccharide) concentration in the hydrolysate while
      hydrolyzing pure (carboxymethyl-cellulose, xylan, avicel and cellobiose) and
      natural (rice husk, rice straw, bagasse and Napier-grass) cellulosic materials.
      The cellulosic hydrolysates from CMC and xylan were successfully converted to
      H(2) via dark fermentation with Clostridium butyricum CGS5, attaining a maximum
      hydrogen yield of 4.79 mmol H(2)/g reducing sugar.

PMID- 19604693
TI  - Isoplatensimycin: Synthesis and biological evaluation.
AB  - Isoplatensimycin, a novel analog of platensimycin, was synthesized via
      intramolecular dipolar cycloaddition of a carbonyl ylide. Isoplatensimycin showed
      little activities against strains of Staphylococcus aureus, but exhibited
      activities against some vancomycin-resistant enteroccoci.

PMID- 19604694
TI  - Piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists
      for inhibition of platelet aggregation.
AB  - Polymer-assisted solution-phase (PASP) parallel library synthesis was used to
      discover a piperazinyl-glutamate-pyridine as a P2Y(12) antagonist. Exploitation
      of this lead provided compounds with excellent inhibition of platelet aggregation
      as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and
      physiochemical properties were optimized leading to compound (4S)-4-[({4-[4
      (methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4
      [(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 22J with good human PRP
      potency, selectivity, in vivo efficacy and oral bioavailability.

PMID- 19604695
TI  - Synthesis and biological evaluation of imidazole derivatives as novel NOP/ORL1
      receptor antagonists: exploration and optimization of alternative pyrazole
      structure.
AB  - Nonpeptidic small-molecule NOP/ORL1 receptor antagonists with an imidazole
      scaffold were designed and synthesized to investigate alternatives to the
      pyrazole analog. Systematic modification of the original pyrazole lead [Kobayashi
      et al., Bioorg. Med. Chem. Lett.2009, 19, 3627; Kobayashi et al., Bioorg. Med.
      Chem. Lett., in press] to change the heterocyclic core, substituted side chain,
      and pendant functional group demonstrated that examining the structure-activity
      relationship for novel templates allowed the identification of potent, fully
      substituted 4-aminomethyl-1H-imidazole and 2-aminomethyl-1H-imidazole. These
      compounds exhibited excellent potency for ORL1 receptor with minimal P-gp efflux
      and/or reduced hERG affinity.

PMID- 19604696
TI  - Discovery of a novel protein kinase B inhibitor by structure-based virtual
      screening.
AB  - Protein kinase B (PKB/AKT) is a promising and attractive therapeutic target in
      anticancer drug development. Herein, we report the findings of virtual screening
      for novel ATP-competitive inhibitors of AKT-2 using 2D- and 3D-similarity
      searching and sequential molecular docking with two crystal structures of AKT-2.
      Our multistep approach led to the identification of a low micromolar AKT-2
      inhibitor (IC(50)=1.5 microM) with a novel scaffold. The experimentally validated
      inhibitor represents the starting point for an optimization program.

PMID- 19604697
TI  - John Bryant Curtis: neurosurgeon, leader and mentor.
AB  - In every generation of neurosurgeons, there are those whose judgment and
      professional accomplishments gain distinction among their peers. Such exceptional
      leaders often exhibit unique talent and inevitably, they exert a lasting
      influence on their field of endeavour. John Bryant Curtis was one of these.
      Rising from humble roots, Curtis made his impact in neurosurgery starting at the
      age of 36. A legendary and a master neurosurgeon for his period, he became the
      second director of Neurosurgery at The Royal Melbourne Hospital, succeeding R. S.
      Hooper in 1967. Like Hooper, Curtis had undertaken a three years Fellowship in
      Oxford at the Radcliffe Infirmary to train under Sir Hugh Cairns in 1947. On his
      return to Australia in 1950, he was among the pioneers in introducing
      percutaneous angiography into the country, which earned him the honourable
      Hunterian Professorship at the Royal College of Surgeons of England in 1958. This
      was in recognition for his contribution to the investigation of intracranial
      aneurysms. Among the many neurosurgeons whom John Bryant Curtis trained at the
      Royal Melbourne Hospital and at the Prince Henry Hospital, he was considered, by
      a few, a controversial figure. Others found the experience very positive. He was
      a distinguished neurosurgeon with expert clinical judgment, but simultaneously a
      stern and formidable character who demanded only the best from his staff and
      trainees. He was contrastingly thoughtful and gentle to his patients. Behind
      every great leader, there is a personal side, often more gentle and vulnerable
      than the public persona. Curtis was a generous, loving, funny, although at times
      eccentric human being. Although he died in 1989, ironically from metastatic brain
      tumours, his dynamic personality and work ethic imprinted a lasting impression on
      those who had met him.

PMID- 19604698
TI  - ssDNA aptamers that recognize diclofenac and 2-anilinophenylacetic acid.
AB  - A series of 56 ssDNA aptamer variants that bind to diclofenac (DCF) were selected
      from an initial pool of 2.4x10(14) ssDNA molecules by Flu-Mag SELEX process.
      Sequence analysis of these aptamer variants showed three major groups based on
      sequence similarity in their random N40 sequences. Out of these, four aptamers
      designated as D10/DA24, D22, D16, and D3 showed high affinity to DCF with K(d)
      values 100.64, 166.34, 148.73, and 42.7 nM, respectively. Secondary structures of
      these aptamers showed highly distinct features with typical stem and loop
      structures. Specificity tests with these four aptamer variants showed that D3
      aptamer had higher specificity to DCF followed by 2-anilinophenylacetic acid
      (2APA), a structural analog of DCF. Whereas aptamers D16 and D22 showed higher
      specificity to 2APA compared to DCF as target used during selection process.
      Further, the D10/DA24 aptamer showed high affinity but no specificity to DCF. The
      DCF aptamers selected can be potential candidates for drug-delivery systems,
      specific detection of DCF and its derivatives in pharmaceutical preparations and
      contaminants.

PMID- 19604699
TI  - UNA (unlocked nucleic acid): a flexible RNA mimic that allows engineering of
      nucleic acid duplex stability.
AB  - UNA (unlocked nucleic acid) monomers are acyclic derivatives of RNA lacking the
      C2'-C3'-bond of the ribose ring of RNA. Synthesis of phosphoramidite UNA building
      blocks of the nucleobases adenine, cytosine, guanine, and uracil is described
      herein together with their incorporation into RNA strands. UNA monomers
      additively decrease nucleic acid duplex stability and can be positioned
      strategically to induce either lack of discrimination of mismatches, that is,
      universal base behavior, or increased discrimination of mismatches, that is,
      improved hybridization specificity. UNA-modified RNA duplexes are shown to
      structurally mimic unmodified RNA duplexes by CD spectroscopy.

PMID- 19604700
TI  - Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3
      yl functional group for photo-affinity labeling.
AB  - A novel radioisotope-free photo-affinity probe containing the 3-(1,1-difluoroprop
      2-ynyl)-3H-diazirin-3-yl functional group was designed and synthesized. This very
      compact functionality is envisaged to allow photochemically-induced coupling of a
      compound to its target followed by click reaction coupling with an azido-biotin
      reagent in order to facilitate purification of the labeled target. In a proof-of
      concept study we have shown that 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl
      functional group could be photolyzed to efficiently furnish the methanol adduct
      23 and that the generated highly unstable carbene does not react with the
      neighboring acetylene moiety. A subsequent click reaction with the azido-biotin
      derivative 25 proceeded smoothly to give triazole 26. This chemical probe should
      thus be of unique value for facilitating identification of the molecular
      structure of the target of a bioactive compound.

PMID- 19604701
TI  - Antimicrobial and immunomodulatory properties of prenylated xanthones from twigs
      of Garcinia staudtii.
AB  - Phytochemical investigation of the methanol extract of the twigs of Garcinia
      staudtii yielded four new prenylated xanthones, staudtiixanthones A-D (1-4),
      along with eleven known compounds. Their structures were determined by analysis
      of 1D and 2D NMR spectra and by comparison of spectroscopic data with those
      previously reported. Some of these compounds have been evaluated for
      antibacterial activity against methicillin-resistant Staphylococcus aureus
      (MRSA). The new compounds were also screened for phagocyte chemiluminescence,
      neutrophil chemotaxis, T-cell proliferation, cytokine production from mononuclear
      cells and cytotoxicity. They were found to exhibit potent immunomodulatory
      activities.

PMID- 19604702
TI  - Cranial surgery without head shaving.
AB  - OBJECTIVE: Based on a series of 632 patients who underwent craniotomy without
      head shaving, we report the efficacy and safety of our simplified procedure and
      document the usefulness of the electrosurgical scalpel. METHODS: After brushing a
      chlorhexidine-alcohol solution onto the craniotomy site, the hair was parted from
      the incision line and fixed with adhesive paper drapes. In recent cases,
      electrosurgical scalpels were used for scalp- and subcutaneous dissection. At the
      end of surgery, the wound was closed in the usual manner, taking care that no
      hair was in the wound and the hair and wound were rinsed with clean water in the
      operating room. We did not apply disinfectant for postoperative wound care,
      rather, the hair was shampooed on the 2nd, 4th, and 6th postoperative day.
      RESULTS: Among 632 patients who underwent cranial surgery without head shaving,
      only 7 (1.1%) developed postoperative wound infections. None of the 34 patients
      who underwent craniotomy using the electrosurgical scalpel developed wound
      infections. CONCLUSIONS: Our simplified cranial surgery without head shaving does
      not increase the risk of wound infection. Because the use of the electrosurgical
      scalpel for skin and soft tissue dissection minimizes bleeding, the probability
      of wound infection appears to be reduced.

PMID- 19604703
TI  - The 'real world' asks for coronary artery bypass grafting.

PMID- 19604704
TI  - The synthesis and photoactivated cytotoxicity of 2-methyl-4-oxo-3-prop-2-yn-1
      ylcyclopent-2-en-1-yl-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
      conjugated with alpha-terthienyl derivatives.
AB  - The synthesis of one pyrethroid insecticide [2-methyl-4-oxo-3-prop-2-yn-1
      ylcyclopent-2-en-1-yl-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
      (Abbrev. JZ) (Fig. 1)] conjugated with a series of alpha-terthienyl derivatives
      (2-8) (Fig. 1) by palladium/copper-catalyzed cross-coupling reaction is presented
      here for evaluating the photoactivated cytotoxicity. The photoactivated
      cytotoxicity on Spodoptera litura (SL) cell line was detected by MTT assay. The
      inhibitory activity of all the conjugates was enhanced in the irradiation
      condition, compared with that of JZ. The IC(50) values of the most effective
      compound 9 (Fig. 1) treated with irradiation were 11.60 microg mL(-1) at 24h and
      8.93 microg mL(-1) at 48 h, respectively. Generation of intracellular reactive
      oxygen species (ROS) and change of mitochondrial transmembrane potential (MMP) on
      SL cells treated with compound 9 were used for the further photoactivated study.
      A summary of these experiments on compound 9 demonstrated the notable ROS
      generation and dramatic MMP decrease when irradiated with UVA light. The results
      also represented statistically significant difference between dark and
      irradiation treatment of compound 9. However, in control and JZ groups, the
      effects were not statistically different. It was proved that our prepared
      compounds were ideal candidates for new photoactivated pyrethroid insecticides.

PMID- 19604705
TI  - Role of structure-proteins in the porphyrin-DNA interaction.
AB  - We studied the complexation of meso-tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)
      with HeLa nucleosomes and compared it to our earlier results on T7 phage
      nucleoprotein complex (NP) and isolated DNA. To identify binding modes and
      relative concentrations of the bound TMPyP forms, the porphyrin absorption
      spectra were analyzed at various base pair/porphyrin ratios. Spectral
      decomposition and circular dichroism measurements proved that the two main
      binding modes of TMPyP, i.e., external binding and intercalation occur also in
      the nucleosomes. The DNA superstructure maintained by the proteins decreases its
      accessibility for TMPyP similarly in both nucleoproteins. A difference is
      observed between the partitioning of the two binding modes: in the case of
      nucleosome the ratio of intercalation to groove-binding is changed from 60/40 to
      40/60 as determined for T7 NP and for isolated DNA-s. Using UV and CD melting
      studies, we revealed that TMPyP destabilizes the DNA-protein interaction in the
      nucleosomes but not in the T7 phage. Lastly, photoinduced reaction of bound TMPyP
      caused alterations in DNA structures and DNA-protein interactions within both
      nucleoprotein complexes; the nucleosomes were found to be more sensitive to the
      photoreaction.

PMID- 19604707
TI  - Day-to-day variation in plasma interleukin-6 concentrations in older adults.
AB  - Interleukin-6 (IL-6) is a pro-inflammatory cytokine commonly used in studies as a
      means of assessing chronic inflammatory status. Despite the use of plasma IL-6 as
      a marker of chronic inflammation few studies exist that examine the variability
      of plasma IL-6 within and between individuals. The purpose of this study was to
      assess inter- and intra-variability of plasma IL-6 concentration in men and
      postmenopausal women. Sixteen healthy postmenopausal women and 5 men completed
      the 2-week study. Fasted venous blood samples were obtained on three consecutive
      mornings for two consecutive weeks (six blood draws per participant). Mean plasma
      IL-6 values were 2.00+/-1.74 pg/mL. Intra-variability was not significantly
      different (p>0.05) however inter-variability was significantly different
      (p<0.05). The index of individuality (II) was 0.20 and the standard error of the
      mean (SEM) was determined to equal 0.16 pg/mL (0.32 pg/mL; 1.96 SEM). An II of
      0.20 demonstrates the need to carefully evaluate changes in plasma IL-6
      concentration instead of utilizing population-based reference norms. In an older
      adult population until plasma IL-6 differences exceed 0.32 pg/mL such values
      could be considered normal fluctuation between trials and most likely not
      attributable to a nutrition intervention.

PMID- 19604706
TI  - Associations of social networks with cancer mortality: a meta-analysis.
AB  - This meta-analysis integrates results of 87 studies on the associations of
      perceived social support, network size, and marital status with cancer survival.
      In controlled studies, having high levels of perceived social support, larger
      social network, and being married were associated with decreases in relative risk
      for mortality of 25%, 20%, and 12%, respectively. Moderator analyses revealed
      that never married patients had higher mortality rates than widowed and
      divorced/separated patients. Associations of social network with mortality were
      stronger in younger patients, and associations of marital status with mortality
      were stronger in studies with shorter time intervals, and in early-stage cancer.
      Relationships varied by cancer site, with stronger associations of social support
      observed in studies of patients with leukemia and lymphomas and stronger
      associations of network size observed in studies of breast cancer. Further
      randomized intervention studies are needed to test causal hypotheses about the
      role of social support and social network for cancer mortality.

PMID- 19604708
TI  - Role of proinflammatory markers and NT-proBNP in patients with an implantable
      cardioverter-defibrillator and an electrical storm.
AB  - BACKGROUND: Several studies have attempted to identify risk factors for the
      development of an electrical storm (ES), which is defined as 3 separate
      ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no
      triggers have been found. However, little is known about the role of inflammation
      and NT-proBNP in patients with ES. The aim of this study was therefore to assess
      the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs
      CRP) and NT-proBNP serum concentrations in ICD-patients with or without single
      spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES. METHODS:
      Markers were determined in 51 patients without ICD-intervention, in 15 ICD
      patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD
      patients with ES (blood sampling performed within 60min after fulfilling ES
      criteria). VT/VF-episodes were analysed by stored ICD-electrograms. RESULTS: All
      patients had idiopathic dilated cardiomyopathy (n=23) or coronary artery disease
      (n=63). Patients with ES revealed significantly higher mean serum concentrations
      of all markers (IL-6 15.19+/-10.34 pg/mL, hs-CRP 20.12+/-14.4 mg/L, NT-proBNP
      4799+/-4596 pg/mL) compared to baseline values of patients with single VT/VF
      events during follow-up (IL-6 8.37+/-5.8 pg/mL (p=0.03), hs-CRP 4.7+/-5.3 mg/dL
      (p<0.001), NT-proBNP 1913+/-2665pg/mL (p=0.04)) and compared to baseline values
      of ICD-patients without device intervention (IL-6 4.62+/-3.66 pg/mL (p<0.001), hs
      CRP 4.1+/-3.4 mg/L (p<0.001), NT-proBNP 1461+/-2281pg/mL (p<0.001)). In 9/20
      patients presenting with ES (45%) baseline values were available. All markers
      were significantly higher during ES compared to event-free determination (IL-6
      14.54+/-10.43 vs. 7.03+/-2.83 pg/mL (p=0.04), hs-CRP 19.07+/-16.07 vs. 6.5+/-3.9
      mg/L (p=0.02), NT-proBNP 4218+/-2561 vs. 2099+/-1279 pg/mL (p=0.03)).
      CONCLUSIONS: Electrical storm is associated with significantly elevated IL-6, hs
      CRP and NT-proBNP serum concentrations in ICD-patients with structural heart
      disease. Thus, ES may be triggered by proinflammatory activity. Combined
      intraindividual elevation of determined markers might help to identify patients
      at risk of impending electrical storm.

PMID- 19604709
TI  - Electrical low-frequency stimulation induces long-term depression of sensory and
      affective components of pain in healthy man.
AB  - Electrical low-frequency stimulation (LFS) of nociceptive skin afferents reliably
      induces long-term depression (LTD) of pain. Recent experiments have assessed the
      effects of LTD on pain perception by using a simple one-dimensional rating scale.
      The psychophysical study investigated the impact of noxious LFS on the sensory
      and affective aspects of pain perception by multidimensional rating scales. In 20
      healthy volunteers, nociceptive fibers of the left hand dorsum were electrically
      stimulated by a concentric electrode. Test stimulation series (15 stimuli each,
      0.125Hz) were performed before (Pre) and after (Post) a conditioning LFS (1Hz,
      20min) or no stimulation period (Control). Pain ratings concerning test
      stimulation and LFS were obtained by multidimensional assessment including Verbal
      rating scale of perceived stimulus intensity (VRS-I) and unpleasantness (VRS-U)
      and pain perception scale with sensory (SES-S) and affective items (SES-A). After
      the conditioning LFS, VRS-I, VRS-U, SES-S, and SES-A decreased as compared to Pre
      series and Control. During conditioning LFS, ratings decreased. Factor analysis
      of SES-S revealed sole reduction of superficial sharp pain perception after
      conditioning LFS in contrast to Control experiment. Perception of deep rhythmic
      pain decreased over time. Deep constant pain and superficial heat pain were not
      affected. Electrical test stimulation via concentric electrode evokes sensory as
      well as affective pain perception. Both components decrease during noxious,
      conditioning LFS and remain depressed for at least one hour. Reduction of sharp
      pain points to Adelta fiber mediated LTD. These results stress the analgesic
      potency of LTD and its possible impact on future therapy in chronic pain.

PMID- 19604710
TI  - 3D H2BC: a novel experiment for small-molecule and biomolecular NMR at natural
      isotopic abundance.
AB  - 3D H2BC is introduced for heteronuclear assignment on natural abundance samples
      even for biomolecules up to at least 10 kDa in low millimolar concentrations as
      an overnight experiment using the latest generation of cryogenically cooled
      probes. The short pulse sequence duration of H2BC is maintained in the 3D version
      due to multiple use of the constant-time delay. Applications ranging from a small
      lipid to a non-recombinant protein demonstrate the merits of 3D H2BC and the ease
      of obtaining assignments in chains of protonated carbons.

PMID- 19604712
TI  - The feasibility of computational modelling technique to detect the bladder
      cancer.
AB  - A numerical technique, finite element analysis (FEA) was used to model the
      electrical properties, the bio impedance of the bladder tissue in order to
      predict the bladder cancer. This model results showed that the normal bladder
      tissue have significantly higher impedance than the malignant tissue that was in
      opposite with the impedance measurements or the experimental results. Therefore,
      this difference can be explained using the effects of inflammation, oedema on the
      urothelium and the property of the bladder as a distensible organ. Furthermore,
      the different current distributions inside the bladder tissue (in histological
      layers) in normal and malignant cases and finally different applied pressures
      over the bladder tissue can cause different impedances for the bladder tissue.
      Finally, it is believed that further studies have to be carried out to
      characterise the human bladder tissue using the electrical impedance measurement
      and modelling techniques.

PMID- 19604713
TI  - Hot and cold contrasts in high-resolution Tc-99m planar scintigraphy: a survey of
      fifty-two camera heads using the PICKER thyroid phantom.
AB  - This study was aimed at comparing the sensitivity and hot and cold contrasts
      obtained when imaging the PICKER thyroid phantom using gamma cameras fitted with
      either their ultra-high or high-resolution low-energy parallel hole collimator.
      Seventeen camera models from Elscint, General Electric, Siemens and Sopha Medical
      Vision were involved in the study for a total of 30 cameras and 52 camera heads.
      A single operator conducted the study in order to minimize the impact of human
      factors. The phantom contained about 74MBq (99m)Tc and was imaged at 10cm from
      the collimator face with the energy window that are recommended by the camera
      manufacturer. A total of 1 million counts were accumulated. Hot and cold
      contrasts were in mean of about 0.05 higher when using an ultra-high-resolution
      than when using a high-resolution low-energy collimator. This higher contrast was
      obtained at the expense of a mean reduction in sensitivity of 30%. In particular,
      Elscint cameras demonstrated a 30% lower sensitivity whatever the collimator
      type. The Sopha Medical Vision DST and DSX cameras and the General Electric
      Magicam camera offered the lowest contrasts among the cameras with a high
      resolution collimator. Although this was accompanied by a higher than the mean
      sensitivity for the DST and DSX, the Magicam demonstrated sensitivity roughly
      identical to the mean of all the cameras with a high-resolution collimator.

PMID- 19604711
TI  - Profiling of oxidative stress in patients with inborn errors of metabolism.
AB  - Free radical formation resulting in oxidative stress is a hallmark of
      mitochondrial dysfunction. Indeed, oxidative stress has been demonstrated to be
      an underlying pathophysiologic process in various inborn errors of metabolism.
      Metabolic profiling of oxidative stress may provide a non-specific measure of
      disease activity that may further enable physicians to monitor disease. In the
      present study, we investigated two markers of oxidative damage in urinary samples
      from IEM subjects and controls: F-2 isoprostanes, a measure of lipid peroxidation
      and di-tyrosine, a measure of protein oxidation. We also determined urinary
      antioxidant activity in these samples. Subsets of IEM patients showed
      significantly higher levels of the damage markers isoprostanes and di-tyrosine.
      Of note, patients with cobalamin disorders (i.e., CblB and CblC) consistently had
      the highest levels of oxidative damage markers. Lower urine antioxidant capacity
      was seen in all subject categories, particularly cobalamin disorders and
      propionic acidemia. Longitudinal studies in subjects with MSUD showed good
      concordance between markers of oxidative damage and acute decompensation.
      Overall, quantifying oxidative stress offers a unique perspective to IEM. These
      measures may provide a means of addressing mitochondrial function in IEM and aid
      in the development of therapeutic targets and clinical monitoring in this diverse
      set of disorders.

PMID- 19604714
TI  - [Comprehensive sexual and contraceptive education for young people].
AB  - According to the National Institute of Statistics (INE) the number of unwanted
      pregnancies in Spain is increasing every year. This is particularly worrying as
      regards unwanted in young people, particularly those under 15, which increased by
      76% from 2001 to 2005. The younger age when people begin sexual relationships,
      the increasingly liberal attitudes, a higher number of sexual partners and high
      risk sexual practices, expose them to very important health problems, such as
      unwanted pregnancies and sexually transmitted diseases (STD). Adolescence is a
      vital phase in the personal and sexual identity process. Sexual Education is
      necessary in a society which seems to be well informed but on the other hand has
      a high proportion of ignorance and errors, which could seriously affect the
      emotional balance of people. Teaching to know and accept their own body, seek
      information or ask for help is an education that can help them to maintain
      healthier and satisfactory relationships. On the other hand, the increase in
      undesired pregnancies and sexually transmitted diseases, including HIV, makes
      this kind of education a priority. Our experience in sexual education for young
      people answers this need. Young people have the right to an effective sexual
      education. Information and comprehensive sexual education provide them with the
      knowledge, skills and attitudes necessary to take decisions in the present and
      future.

PMID- 19604715
TI  - [Descriptive study of nursing-sensitive outcomes in oncohematological patients
      and nursing interventions].
AB  - OBJECTIVE: To assess the main nursing-sensitive outcomes in oncohematological
      patients admitted to hospital and to evaluate nursing interventions. MATERIAL AND
      METHODS: We performed a prospective, observational study in the oncohematological
      units of the Morales Meseguer Hospital. The sample included patients admitted
      from March 2006 to June 2007. RESULTS: A total of 56 patients were studied. Of
      these, 39 patients (69.6%) had some degree of mucositis but only six patients
      (10.7%) were assessed objectively by nurses. Fifty-two patients (92.9%) received
      anti-emetic treatment, but there were no reports of nausea or vomiting in 27
      (48.2%). Ten patients (17.9%) were referred to the nutritional unit. Anxiety
      levels and psychosocial impact decreased during hospital admission and patient
      satisfaction increased but family members experienced greater stress. Pressure
      ulcer developed in only one patient. Four catheters (8.2%) became infected and
      there were five cases of catheter-related bacteremia. There were 22 cases of
      catheter obstruction (39.9%). CONCLUSIONS: The incidence of mucositis, pressure
      ulcer and catheter-related bacteremia was lower than in other studies. There was
      no standard assessment of pain, nausea or vomiting. Anxiety levels were lower
      than in other studies. Improvement and psychosocial adjustment suggested a
      process of adaptation to the disease. The increase in caregiver burden was
      related to the disease in the long term. Satisfaction with nursing care was 55
      points on a 70-point scale.

PMID- 19604716
TI  - [Pseudoscience].

PMID- 19604717
TI  - The dextropropoxyphene controversy.

PMID- 19604719
TI  - The REM sleep behavior disorder screening questionnaire: validation study of a
      Japanese version.
AB  - BACKGROUND: REM sleep behavior disorder (RBD) is a parasomnia characterized by
      intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate
      motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known
      association with neurodegenerative diseases such as synucleinopathies. Recently,
      a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ)
      was validated. Detection of RBD using a Japanese version of the RBDSQ would be
      useful in the stepwise diagnostic process. We investigated the validity and
      reliability of a Japanese version of this instrument, the RBDSQ-J. METHODS:
      Subjects were 52 patients with iRBD diagnosed according to criteria in the
      International Classification of sleep disorders, second edition, 55 obstructive
      sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a
      diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65
      healthy subjects. RESULTS: An RBDSQ-J score cut-off of 5.0 was considered useful
      for differentiating the iRBD group from the healthy subjects or the OSAS group.
      Cronbach's alpha for the entire RBDSQ-J was 0.866. CONCLUSION: The RBDSQ-J had
      high sensitivity, specificity, and reliability and would be applicable as a
      screening method for iRBD in the elderly Japanese population.

PMID- 19604718
TI  - Identifying the species-origin of faecal droppings used for avian influenza virus
      surveillance in wild-birds.
AB  - BACKGROUND: Avian influenza virus (AIV) surveillance in birds is important for
      public health. Faecal droppings from wild-birds are more readily available for
      such studies, but the inability to identify the species-origin of faecal samples
      limits their value. OBJECTIVES: To develop, optimise, and field-test a method to
      simultaneously detect AIV and identify the species-origin from faecal samples.
      STUDY DESIGN: Analytical sensitivity of the species-identification RT-PCR was
      assessed on serial dilutions of faecal droppings. Overall sensitivity of the
      methods for species-identification and AIV detection was assessed on 92 faecal
      and cloacal samples collected from wildlife, poultry markets, and experimentally
      H5N1-infected birds. RESULTS: All 92 samples were correctly identified to 24
      different species, with a detection limit of 2.8mug of faecal material. All 20
      specimens previously shown by virus culture to be positive for influenza virus
      were correctly identified by RT-PCR for influenza A using the same nucleic-acid
      extracts used for species-identification. CONCLUSION: We have optimised and
      evaluated a method for identifying the species of origin and detecting AIV from
      bird faecal droppings that can be applied to routine surveillance of influenza
      viruses in wild-birds.

PMID- 19604720
TI  - Rolling circle amplification and multiplex allele-specific PCR for rapid
      detection of katG and inhA gene mutations in Mycobacterium tuberculosis.
AB  - The aim of the study was to compare a novel, rolling circle amplification (RCA)
      assay for detection of common isoniazid (INH) resistance mutations in
      Mycobacterium tuberculosis with a multiplex allele-specific PCR (MAS-PCR) and
      sequencing of katG and the fabG1-inhA promoter region. One or more mutations were
      identified by RCA, MAS-PCR, and sequencing in 21 (68%), 22 (71%), and 23 (74%),
      respectively, of 31 epidemiologically unrelated INH-resistant isolates, and in
      none of 8 INH-susceptible isolates. The RCA assay is a rapid, inexpensive, and
      practical screening method for INH resistance in M. tuberculosis in countries
      with high prevalence of INH resistance.

PMID- 19604721
TI  - Regional differences in serotype distribution, pneumococcal vaccine coverage, and
      antimicrobial resistance of invasive pneumococcal disease among German federal
      states.
AB  - Continuous nationwide surveillance of invasive pneumococcal disease has been
      conducted in Germany for more than 15 years. In this study, 3724 isolates were
      included. A total of 2065 isolates were obtained from children under 16 years of
      age from 1997 to 2006, and 1659 isolates were obtained from adults aged 16 years
      and older between 2002 and 2006. Results were classified to federal states, and
      supra-regional trends were illustrated by classifying the federal states into the
      regions 'North-West', 'North-East' and 'South'. Among childhood isolates, the
      most common serotypes were 14 (26.4%), 6B (7.7%), 23F (7.4%), 19F (7.1%), 1
      (7.0%), 18C (6.2%), and 7F (5.6%). Serotype coverage for the 7-valent conjugate
      vaccine was 62.3%. For the 10-valent and 13-valent vaccines (both in development)
      the coverage was 75.5% and 84.8%, respectively. The 23-valent polysaccharide
      vaccine had a coverage of 87.3%. The coverage varies considerably among the
      federal states. Penicillin G resistance was observed in 7.4% of meningitis cases.
      In the non-meningitis group, no intermediate resistant or resistant strains were
      detected. Among adults, the most common serotypes were 14 (16.9%), 3 (9.2%), 4
      (7.8%), 7F (7.5%), 1 (6.8%), and 9V (6.1%). Serotype coverage for the 7-valent
      conjugate vaccine was 46.5%. For the pneumococcal conjugate vaccines in
      development, the coverage was 61.1% (10-valent) and 76.3% (13-valent). The 23
      valent polysaccharide vaccine had a coverage of 88.7%. Penicillin G resistance
      was observed in 6.4% of meningitis cases. Among these, considerably higher rates
      of resistance were observed in the North-East region (13.0%) than in the North
      West (7.1%) and South (1.8%) regions.

PMID- 19604723
TI  - Evidence-based practice: sowing the seeds for success.

PMID- 19604722
TI  - Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected
      patients with stage IIIB non-small-cell lung cancer: a multicentre phase II
      trial.
AB  - BACKGROUND: Stage IIIB non-small-cell lung cancer (NSCLC) is usually thought to
      be unresectable, and is managed with chemotherapy with or without radiotherapy.
      However, selected patients might benefit from surgical resection after
      neoadjuvant chemotherapy and radiotherapy. The aim of this multicentre, phase II
      trial was to assess the efficacy and toxicity of a neoadjuvant chemotherapy and
      radiotherapy followed by surgery in patients with technically operable stage IIIB
      NSCLC. METHODS: Between September, 2001, and May, 2006, patients with
      pathologically proven and technically resectable stage IIIB NSCLC were
      sequentially treated with three cycles of neoadjuvant chemotherapy (cisplatin
      with docetaxel), immediately followed by accelerated concomitant boost
      radiotherapy (44 Gy in 22 fractions) and definitive surgery. The primary endpoint
      was event-free survival at 12 months. Efficacy analyses were done by intention to
      treat. This trial is registered with ClinicalTrials.gov, number NCT00030810.
      FINDINGS: 46 patients were enrolled, with a median age of 60 years (range 28-70).
      13 (28%) patients had N3 disease, 36 (78%) had T4 disease. All patients received
      chemotherapy; 35 (76%) patients received radiotherapy. The main toxicities during
      chemotherapy were neutropenia (25 patients [54%] at grade 3 or 4) and febrile
      neutropenia (nine [20%]); the main toxicity after radiotherapy was oesophagitis
      (ten patients [29%]; nine grade 2, one grade 3). 35 patients (76%) underwent
      surgery, with pneumonectomy in 17 patients. A complete (R0) resection was
      achieved in 27 patients. Peri-operative complications occurred in 14 patients,
      including two deaths (30-day mortality 5.7%). Seven patients required a second
      surgical intervention. Pathological mediastinal downstaging was seen in 11 of the
      28 patients who had lymph-node involvement at enrolment, a complete pathological
      response was seen in six patients. Event-free survival at 12 months was 54% (95%
      CI 39-67). After a median follow-up of 58 months, the median overall survival was
      29 months (95% CI 16.1-NA), with survival at 1, 3, and 5 years of 67% (95% CI 52
      79), 47% (32-61), and 40% (24-55). INTERPRETATION: A treatment strategy of
      neoadjuvant chemotherapy and radiotherapy followed by surgery is feasible in
      selected patients. Toxicity is considerable, but manageable. Survival compares
      favourably with historical results of combined treatment for less advanced stage
      IIIA disease. FUNDING: Swiss Group for Clinical Cancer Research (SAKK) and an
      unrestricted educational grant by Sanofi-Aventis (Switzerland).

PMID- 19604724
TI  - Activation of cryptic IgG reactive with BAFF, amyloid beta peptide and GM-CSF
      during the industrial fractionation of human plasma into therapeutic intravenous
      immunoglobulins.
AB  - The mechanisms of therapeutic action of IVIg are still unclear in most autoimmune
      and inflammatory diseases. IVIg have been shown to bind to a variety of human
      proteins including BAFF, amyloid beta peptide and GM-CSF. It has been suggested
      that this autoreactivity could contribute to the therapeutic immunomodulatory
      effects of IVIg. In this work, we showed that native IgG purified from plasma
      under non-denaturing conditions were much less autoreactive than IVIg. However
      the native IgG autoreactivity with BAFF, amyloid beta peptide and GM-CSF was
      significantly increased by short incubation under the slightly denaturing
      conditions used during industrial plasma fractionation. We conclude that the
      relatively mild conditions used in industrial plasma fractionation are
      sufficiently denaturing to activate a significant amount of cryptic autoreactive
      plasma IgG which could be involved not only in the therapeutic immunomodulatory
      effects of IVIg but also in the adverse "allergic" reactions often observed in
      IVIg-infused patients.

PMID- 19604725
TI  - Effect of variation in ITGAE on risk of sarcoidosis, CD103 expression, and chest
      radiography.
AB  - The integrin alpha(E)beta(7) is believed to play a key role in retention of
      lymphocytes in mucosal tissues of gut, urogenital tract and lung. Five common
      single nucleotide polymorphisms spanning ITGAE, the gene encoding the alpha(E)
      (CD103) unit, were genotyped in 556 sarcoidosis patients and 465 controls. The 
      1088 A/G polymorphism was associated with sarcoidosis (P=0.004). An increased
      risk of disease was found for homozygous carriers of the A allele vs. carriers of
      the G allele (P=0.001, odds ratio=1.63 [1.22-2.17]). Analysis of lymphocytes from
      bronchoalveolar lavage and in vitro functional tests showed higher percentages of
      CD103+CD4+ T cells for the sarcoidosis risk genotype. Radiographic staging at
      disease outcome revealed prevalence of -1088 AA genotype in patients with
      fibrosis (P=0.01). A higher proportion of CD103+CD4+ T cells and ITGAE -1088 AA
      genotype might be associated with fibrosis formation in pulmonary sarcoidosis.

PMID- 19604726
TI  - Risk factors for small for gestational age infants.
AB  - There are many established risk factors for babies who are small for gestational
      age (SGA) by population birth weight centiles (usually defined as <10th centile).
      The confirmed maternal risk factors include short stature, low weight, Indian or
      Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use.
      Maternal medical history of: chronic hypertension, renal disease, anti
      phospholipid syndrome and malaria are associated with increased SGA. Risk factors
      developing in pregnancy include heavy bleeding in early pregnancy, placental
      abruption, pre-eclampsia and gestational hypertension. A short or very long inter
      pregnancy interval, previous SGA infant or previous stillbirth are also risk
      factors. Paternal factors including changed paternity, short stature and father
      born SGA also contribute. Factors associated with reduced risk of SGA or
      increased birth weight include high maternal milk consumption and high intakes of
      green leafy vegetables and fruit. Future studies need to investigate risk factors
      for babies SGA by customised centiles as these babies have greater morbidity and
      mortality than babies defined as SGA by population centiles.

PMID- 19604727
TI  - The experience of seizures after epilepsy surgery.
AB  - Postoperative seizures occur in 20-60% of patients who have epilepsy surgery.
      Despite this, there is limited understanding of a patient's experience of the
      recurrence of seizures after surgery. This study used a qualitative approach to
      identify key themes derived from content analysis of 15 in-depth patient
      interviews about the experience of seizure recurrence. The results showed a
      prominence of psychological issues over medical concerns. The four most
      frequently expressed themes were perceived success of surgery, medication,
      acceptance of seizure recurrence, and personal independence. Despite seizure
      recurrence, patient sentiments were not universally negative; rather there was
      heterogeneity of views, with some reporting ambivalence and others a sense of
      satisfaction with outcome. The findings provide evidence for the importance of
      cognitive reframing and benefit finding in the context of seizure recurrence.

PMID- 19604729
TI  - An application of high-speed counter-current chromatography coupled with
      electrospray ionization mass spectrometry for separation and online
      identification of coumarins from Peucedanum praeruptorum Dunn.
AB  - A new and systematic application for separation and online identification of
      coumarins from Peucedanum praeruptorum Dunn by preparative high-speed counter
      current chromatography coupled with electrospray ionization multi-stage mass
      spectrometry (prep-HSCCC/ESI-MS(n)) was established. The procedure of separation
      was guided by the chromatogram of ion current. The structures of acquisitions
      were deduced by MS information. The hyphenation between prep-HSCCC/ESI-MS(n) was
      designed to keep the split ratio from 1:20 to 1:200 exactly. Seven compounds were
      obtained and two new compounds were detected. It was proved that prep-HSCCC/ESI
      MS(n) was an effective method for sensitive detection, rapid identification and
      separation of natural products.

PMID- 19604728
TI  - Serum matrix metalloproteinases in adult CF patients: Relation to pulmonary
      exacerbation.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) virtually degrade all components of
      the extracellular matrix and are mainly expressed in tissues following
      inflammation or remodeling. Increased expression of certain MMPs in sputum and
      bronchoalveolar lavage of patients with cystic fibrosis (CF) is related to
      impaired lung function. We investigated whether a panel of serum MMPs is
      associated with both, impairment of pulmonary function and occurrence of
      pulmonary exacerbations (PEx) in adult patients with CF. METHODS: Serum
      concentrations of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, and
      TIMP-1 were determined by ELISA in 54 adult CF patients. PEx was defined based on
      a score established by Rosenfeld in 2001. MMP-1, MMP-8, MMP-9 and TIMP-1 were
      assessed in 7 CF patients with PEx before and after systemic antibiotic therapy.
      RESULTS: Of the 54 CF patients, PEx was diagnosed in 16 different CF patients.
      Compared to healthy controls, MMP-1, MMP-8, and MMP-9, serum levels were elevated
      in CF patients and correlated with PEx. MMP-8 expression was associated with
      impaired lung function. For MMP-2, we observed a decreased expression and an
      association of MMP-2 decline with PEx. Antibiotic treatment of CF patients with
      PEx led to a decrease of MMP-1, MMP-8 and active MMP-9 protein concentration.
      CONCLUSIONS: Increased serum expression of certain MMPs is associated with
      occurrence of PEx and impaired lung function in CF. Hence, these MMPs might serve
      as surrogate markers for PEx.

PMID- 19604730
TI  - Novel molecularly imprinted polymers for the selective extraction and
      determination of metoclopramide in human serum and urine samples using high
      performance liquid chromatography.
AB  - This work was performed in order to study the possibilities in using molecularly
      imprinted polymers (MIPs) as sorbent material in solid-phase extraction (MISPE)
      for the sample clean-up technique for the determination of metoclopramide (MCP)
      in biological fluids. The effective factors influencing the bulk polymerization
      have been studied. Molecular recognition properties, binding capability and
      selectivity of the molecularly imprinted polymers (MIPs) were evaluated and the
      results revealed the obtained MIPs have high affinity for MCP in aqueous
      environment. The optimal conditions for solid-phase extraction (SPE) consisted of
      conditioning with 1 mL of methanol and 1 mL of deionized water at neutral pH,
      loading with 1 mL of the water sample (50 microg L(-1)) at pH 8.5, washing using
      1 mL of acetone and elution with 2x 1 mL methanol/acetic acid (10/1, v/v). After
      optimization of SPE procedure, the MIP was then directly used to selectively
      extract the target drug from human serum and urine with an extraction recovery of
      more than 90%. Chromatograms of the eluate solutions show an efficient clean-up,
      which supports the potential of MISPE for clean-up of trace amounts of MCP from
      serum and urine. The limits of detection of MCP in human serum and urine were 3
      and 1.2 microg L(-1), respectively.

PMID- 19604731
TI  - High-performance liquid chromatography-tandem mass spectrometry for the
      determination of pidotimod in human plasma and its application to a
      pharmacokinetic study.
AB  - A selective, rapid and sensitive high-performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) method was developed for the first time to
      determine pidotimod in human plasma and applied to a pharmacokinetic study.
      Diphenhydramine was used as the internal standard (I.S.). Sample pretreatment
      involved in one-step protein precipitation (PPT) with methanol of 0.1 mL plasma.
      The analysis was carried out on an Ultimate XB-C(8) column with mobile phase of
      methanol-water containing 0.5% formic acid (65:35, v/v). The detection was
      performed on a triple quadrupole tandem mass spectrometer by multiple reaction
      monitoring (MRM) mode via electrospray ionization (ESI) source. Each plasma
      sample was chromatographed within 4.5 min. The linear calibration curves were
      obtained in the concentration range of 0.05-20.00 microg/mL (r(2) > or = 0.99)
      with the lower limit of quantification (LLOQ) of 0.0500 microg/mL. The intra- and
      inter-day precision (relative standard deviation, R.S.D.) values were below 15%
      and accuracy (relative error, R.E.) was from -5.1% to 3.9% at all quality control
      (QC) levels. The method was applicable to clinical pharmacokinetic study of
      pidotimod in healthy volunteers after oral administration.

PMID- 19604732
TI  - Re: Sam Loewenberg's article, "Cancer policy in the Obama administration".

PMID- 19604733
TI  - Primary biliary cirrhosis-specific autoantibodies in patients with systemic
      sclerosis.

PMID- 19604734
TI  - [Sarcoidosis: a systemic form in a four year-old child].

PMID- 19604735
TI  - [Acute thyroiditis due to actinomyces].

PMID- 19604736
TI  - [Cervicocephalic arterial dissection. Abnormal origin of the posterior cerebral
      artery].

PMID- 19604737
TI  - [Choreoathetosis after Herpes simplex encephalitis].
AB  - After Herpes simplex encephalitis, 25% of cases may have a relapse, rarely as a
      choreoathetosic movement disorder. The anatomic basis for herpes simplex virus
      encephalitis-associated movement disorders remains poorly understood, but the
      hypothesis is that it may be due to a post-infectious immune-mediated process. We
      report an 8-month-old boy, with herpes simplex encephalitis type 1, who started
      with an extrapyramidal Syndrome, presenting with choreoathetosis and ballistic
      movements, three weeks after onset. These new symptoms were attributed to a post
      infectious immune-mediated process. We treated our patient with corticosteroids
      at high dose and gamma-globulins, in addition to a new course of Acyclovir.
      Sedation was required to control the intense choreoathetosic movements.
      Tetrabenazine was also tried, unsuccessfully. We studied a mutation on the toll
      like receptors (TLR3), which has been related to susceptibility for the disease,
      which was negative.

PMID- 19604738
TI  - [Invasive mechanical ventilation in cystic fibrosis: Influence in lung
      transplant].
AB  - INTRODUCTION: Invasive mechanical ventilation (IMV) in patients with advanced
      cystic fibrosis (CF) is a relative contraindication for lung transplant (LT) in
      adults, although there is currently no data on children. PATIENTS AND METHODS: An
      8-year retrospective study on 21 children with CF who underwent LT was performed,
      analysing their results as they were receiving (n = 8) or not (n = 13) IMV
      pretransplant. Demographic and surgical data, postoperative course, lung function
      and survival (immediate and 1-year) were compared between both groups. The role
      of the IMV pretransplant as a postoperative risk factor was estimated (odds
      ratio) and Kaplan Meier survival study was performed in both groups. RESULTS: No
      differences in patient age, sex and nutritional parameters were observed between
      both groups. Those on IMV who received LT required more frequent and longer
      bypass, more need for tracheotomy, a higher number of rejection episodes per
      patient and multiorgan failure, longer PICU stay and longer time on IMV than
      those who were not on IMV when LT was received. Nevertheless, no differences
      could be found regarding graft function and immediate and 1-year survivals (62.5%
      vs. 92.3% with and without IMV respectively). On the other hand, long-term
      survival was significantly lower than in patients on IMV. CONCLUSIONS: In our
      experience, children with CF on IMV who receive LT have more complicated surgery
      and immediate postoperative course. Though immediate and 1-year results and
      survivals may be encouraging, medium and long-term ones are significantly lower.

PMID- 19604739
TI  - Plastic surgery and Munchausen's syndrome: 'surgeon, beware!'.

PMID- 19604740
TI  - The utility of Alloderm in hand resurfacing.
AB  - Alloderm as a biomechanical scaffold in situations such as skin grafting has been
      previously demonstrated. In this paper we describe its utility in a broad range
      of post-traumatic and congenital hand defects. During the recent three years, 11
      patients (7 male, 4 female) ranging in age from 8 to 84 years underwent hand
      resurfacing using acellular dermis graft. There were 10 traumatic and 1
      congenital hand deformities (constriction ring syndrome). The acellular dermis
      was used as both a dermal filler and as a spacer construct. There was no obvious
      loss of the acellular dermis or infection. Stable resurfacing was achieved in all
      patients with reasonable functional and cosmetic outcomes.

PMID- 19604741
TI  - Use of a patient linked data warehouse to facilitate diabetes trial recruitment
      from primary care.
AB  - Recruitment into clinical trials from primary care may be difficult. Our aim was
      to use the Secure Anonymised Information Linkage (SAIL) databank to identify
      potential participants for two factitious trials. We identified 284 and 711
      participants for each study (population=250,086). This method appears promising
      in identifying trial participants.

PMID- 19604742
TI  - Editorial preface.

PMID- 19604743
TI  - Evidence for a projection to the thalamus from the external cuneate nucleus in
      the monkey.

PMID- 19604744
TI  - Retrograde axonal transport of horseradish peroxidase from spinal cord to brain
      stem cell groups in the cat.

PMID- 19604745
TI  - Stimulation-induced uptake of horseradish peroxidase by rat cortical synapses.

PMID- 19604746
TI  - Reversal of deprivation effects in the lateral geniculate nucleus of the cat.

PMID- 19604748
TI  - Rearing in an acoustically unusual environment - effects on neural auditory
      responses.

PMID- 19604747
TI  - Pursuit eye movements elicited by muscle afferent information.

PMID- 19604749
TI  - On the specificity of 6-hydroxydopamine-induced degeneration of central
      noradrenaline neurons after intracerebral injection.

PMID- 19604750
TI  - Evidence for involvement of central NA neurones in alcohol intake. Increased
      alcohol consumption after degeneration of the NA pathway to the cortex cerebri.

PMID- 19604751
TI  - Restricted mobility of neuronal membrane antigens.

PMID- 19604752
TI  - The neurotropic action of ACTH: effects of ACTH-like peptides on the
      incorporation of leucine into protein of brain stem slices from hypophysectomized
      rats.

PMID- 19604754
TI  - Circadian rhythm of vigilance in rats: modulation by short light-dark cycles.

PMID- 19604753
TI  - General anaesthetics: synaptic depression consistent with increased membrane
      fluidity.

PMID- 19604755
TI  - Letters to the editor.

PMID- 19604756
TI  - Labelling of cells in the medulla oblongata and the spinal cord of the monkey
      after injections of horseradish peroxidase in the thalamus.
AB  - Injections of horseradish peroxidase were performed in macaque monkeys in the
      intralaminar and the ventroposterior thalamic region, respectively. Following
      injection in the intralaminar region labelled cells were present in the marginal
      zone both in the spinal trigeminal nuclues and in the spinal dorsal horn. The
      same areas contained labelled cells after injections in the ventroposterior
      thalamic region, but in such experiments labelled cells were also present in the
      lamina IV-V region of the spinal cord, in the gracile and main cuneate nuclei and
      in the external cuneate nucleus. Thus, the marginal zone of the spinal cord
      appears to project to at least two of the thalamic regions receiving
      spinothalamic fibres in the monkey.

PMID- 19604757
TI  - The central cervical nucleus - A source of spinocerebellar fibres, demonstrated
      by retrograde transport of horseradish peroxidase.
AB  - Injections of horseradish peroxidase in the cerebellum of kittens resulted in
      labelling of cells in the central cervical nucleus (CCN) in the upper cervical
      spinal cord. The largest number of labelled CCN neurones was found after
      injections including the anterior part of the anterior lobe of the cerebellum. In
      this neuronal system horseradish peroxidase was transported at a maximal velocity
      of about 150 mm/day.

PMID- 19604758
TI  - Histochemical support for a dopaminergic mechanism in the dendrites of certain
      periglomerular cells in the rat olfactory bulb.
AB  - With the Vibratome modification of the Falck-Hillarp technique, and with the
      indirect immunofluorescence technique for visualizing the first three enzymes in
      catecholamine synthesis, evidence has been obtained that in the rat olfactory
      bulb several periglomerular cells are dopaminergic. Both tyrosine hydroxylase and
      dopadecarboxylase, converting tyrosine to DOPA and DOPA to dopamine (DA),
      respectively, but not dopamine-beta-hydroxylase, converting DA to noradrenaline,
      are present in periglomerular cell bodies, as well as in their intraglomerular
      dendrites. These findings suggest that DA may be active at dendrodentritic
      synapses known to be present between periglomerular and mitral and/or tufted
      cells.

PMID- 19604759
TI  - Human neuroblastoma: Glial induced morphological differentiation.
AB  - Rat C-6 glioma cells release a factor into culture medium which induces
      morphological differentiation in the IMR-32 human neuroblastoma cell line. The
      time course of differentiation and the effects on cell growth differ from those
      observed in mouse neuroblastoma cells. The effects of other cell lines and the
      relationship of differentiation to cell growth are discussed.

PMID- 19604760
TI  - Postnatal ontogenesis of potentials elicited in the cerebral cortex by afferent
      stimulation.
AB  - The activation of immature rat S1 neocortex by electrical stimulation of
      peripheral nerves and of the thalamus is described. The existence of a surface
      positive potential of intracortical origin at an early stage of development is
      confirmed. It is also shown that both the augmenting and the recruiting phenomena
      can be obtained by thalamic stimulation at postnatal days 3-4.

PMID- 19604761
TI  - Contribution of single motoneurons to renshaw cell activity.
AB  - Single spinal alpha motoneurons driven by injected current are shown to increase
      the activity of Renshaw cells. This fact is a necessary condition for the
      validity of hypotheses concerning the functional significance of recurrent
      inhibition which are based on the conception that individual motoneurons can
      interact with each other.

PMID- 19604762
TI  - Effect of apomorphine on the GABA turnover in the DA cell group rich area of the
      mesencephalon. Evidence for the involvement of an inhibitory gabergic feedback
      control of the ascending DA neurons.
AB  - The effects of the DA receptor agonist apomorphine have been studied in the DA
      cell body rich region of the rat ventral forebrain by measuring the GABA levels
      after inhibition of the GABA aminotransferase with the help of gamma-l
      glutamylhydrazide (GAH). Apomorphine plus GAH resulted in a significant increase
      of GABA levels compared with treatment with GAH alone. This increase was blocked
      by prior treatment with a DA receptor blocking agent, pimozide. Apomorphine and
      pimozide given alone did not modify GABA levels in the ventral midbrain with the
      doses and time-intervals used. It is therefore suggested that the DA cell body
      groups in the mesencephalon, especially the A9 and A10 groups, are under the
      inhibitory influence of GABA neurons which may be involved in the feedback
      control of ascending DA pathways, particularly the mesolimbic DA neurons [8-10].

PMID- 19604763
TI  - The effect of ketamine on nerve conduction in isolated sciatic nerves of the
      toad.
AB  - The actions of 100-2500 mug ketamine hydrochloride per ml Ringer solution were
      examined on the various components of the compound nerve volley of isolated
      sciatic-tibial nerves of toads. The smaller diameter fibres were blocked first
      and fibres of progressively larger diameter were blocked with increasing ketamine
      concentration. A progressive reducton in conduction velocities and amplitude, as
      well as increasing thresholds, accompanied increased drug contact and
      concentration. A preliminary trial on human volunteers revealed an apparent loss
      of pain and thermal sensations following subcutaneous injection.

PMID- 19604764
TI  - Environmental complexity does affect scopolamine induced changes in activity.
AB  - Scopolamine increases ambulation and rearing when animals are tested in a simple
      open field but decreases these responses when they are tested in complex
      environments. The nature of the testing environment, in particular its
      complexity, may therefore need to be considered more closely when the effects of
      psychotropic drugs are being assessed.

PMID- 19604765
TI  - Letter to the editor.

PMID- 19604766
TI  - Morphological correlates of visual field transformation in the corpus callosum.
AB  - Horseradish peroxidase (HRP) injections at the boundary of areas 17 and 18 in cat
      visual cortex resulted in retrograde labelling of neurones located in
      contralateral areas 17 and 18. The HRP-positive neurones were spread over a
      region located around the representation of the vertical meridian; they were most
      numerous in the locus for area centralis. Layer III pyramidal cells and stellate
      cells in upper layer IV were identified as the principal neurones of origin of
      the visual callosal pathway.

PMID- 19604767
TI  - Substantia nigra projections to the reticular formation, superior colliculus and
      central gray in the rat, cat and monkey.
AB  - After horseradish peroxidase injections in different parts of the lower brain
      stem retrogradely labeled neurons were observed in the substantia nigra, mainly
      ipsilateral pars reticulata. These findings demonstrate that the substantia nigra
      projects not only to the striatum and thalamus but also to brain stem areas which
      give rise to descending spinal projections. These nigral projections to brain
      stem structures may play an important role in a variety of behaviors and may be
      involved in clinical syndromes associated with nigral lesions.

PMID- 19604768
TI  - A prefronto-amygdaloid projection in the monkey: light and electron microscopic
      evidence.
AB  - Unilateral partial ablations of the medial prefrontal cortex were made in rhesus
      and cynomolgus monkeys. The course and termination of prefrontoamygdaloid fibers
      were followed with the Nauta-Gygax and Fink-Heimer silver methods, and the
      presence of terminal degeneration in the amygdala was confirmed by electron
      microscopy. The heaviest prefrontal projection appeared to be to the pars
      lateralis of the basal amygdaloid nucleus.

PMID- 19604769
TI  - Maintenance of bulk isolated neurons.
AB  - Neuronal perikarya, obtained from rat brain, can be maintained for a defined
      period of time. As a measure of functional integrity, the ability of neurons to
      incorporate radioisotopically labeled precursors into a TCA insoluble fraction is
      presented.

PMID- 19604770
TI  - Effect of transposition on contractile and histochemical properties of muscle.
AB  - In 16 rats, the extensor digitorum longus (EDL) - a fast muscle - was grafted,
      complete with its innervation, into the bed of the (removed) soleus - a slow
      muscle. Following the transposition, performed on one side only, EDL recovered
      and showed the contraction time of the contralateral EDL that served as control.
      However, as demonstrated histochemically, the transposed EDL exhibited a
      different succinic dehydrogenase activity: it acquired the muscle fiber pattern
      of the slow red soleus muscle. This method of transposition of muscle plus nerve
      allows the study of nerve-muscle relationships with respect to a multiple
      regulation of muscle properties, including the decisive role of neuronal
      specificity and other mechanisms such as substrate (oxygen) supply.

PMID- 19604771
TI  - Reserpine-induced changes in dopamine-beta-hydroxylase activity in the terminal
      projections of the nucleus locus coeruleus.
AB  - Rats received daily subcutaneous injections of reserpine (2.5 mg/kg) for 3 days.
      Dopamine-beta-hydroxylase (DBH) activity was measured in the dorsal pons (which
      contained the locus coeruleus), cerebellum, hippocampus and frontal cortex 1, 2
      and 4 weeks after the last injection. In accordance with previous reports,
      reserpine significantly increased DBH activity in dorsal pons 1 and 2 weeks after
      reserpine. In the other brain regions, which contain noradrenergic terminals of
      the locus coeruleus, reserpine either produced no change in DBH activity
      (cerebellum) or resulted in significant decreases in enzyme activity 1-4 weeks
      after the last injection (hippocampus and frontal cortex). Induction of DBH in
      the locus coeruleus is not, therefore, subsequently reflected in an overall
      increase in enzyme activity in the terminals arising from this nucleus; on the
      contrary, reserpine produces long-term decreases in DBH activity in these
      regions.

PMID- 19604772
TI  - Fate of noradrenaline storage vesicles after release.
AB  - Using [(3)H]noradrenaline (NA), changes in vesicular NA content and storage
      capacity of rat heart ventricles resulting from 24 h cold stress have been
      measured. NA content was decreased to 63% of control value; uptake of [(3)H]NA
      was the same in control and cold treated animals, while NA storage capacity was
      decreased to 78% of control value. This suggests that vesicles are not
      immediately available for re-use after NA release. After cold stress the degree
      of saturation of the vesicular storage capacity was reduced to 78% of control
      value, suggesting a change in the balance of NA synthesis and storage.

PMID- 19604773
TI  - Evidence for heterogeneity in the association properties of the gamma protein of
      mouse 7S nerve growth factor protein.
AB  - The mouse 7S nerve growth factor gamma subunit, which is homogeneous with respect
      to molecular weight and heterogeneous with respect to charge, has been found to
      display heterogeneous self-association behavior at pH values 4 and 7.4.

PMID- 19604774
TI  - Stimulation of the medial forebrain bundle: behavioral dissociation of its
      rewarding and activating effects.
AB  - Non-contingent electrical stimulation of the medial forebrain bundle with low
      current intensities which did not support self-stimulation behavior produced
      drastic motor activation and sniffing. In addition, self-stimulation was
      triggered only if current intensities were strong enough to produce aversion when
      forced-delivered. These results suggest that stimulation of the medial forebrain
      bundle involves both drive activating and rewarding components and that a
      sufficient activation of the first component is essential for the maintenance of
      self-stimulation behavior.

PMID- 19604775
TI  - Thyrotropin releasing hormone (TRH)-containing nerve terminals in certain brain
      stem nuclei and in the spinal cord.
AB  - With the indirect immunofluorescence technique the localization of thyrotropin
      releasing hormone (TRH) has been studied in the lower brain stem and spinal cord.
      Networks of TRH-positive nerve terminals were observed in many cranial nerve cell
      nuclei and around the motoneurons in the spinal cord.

PMID- 19604776
TI  - Abnormal S-potentials recorded from isolated fish retinae and their relation to
      retinal neurotransmission.
AB  - Intracellular recordings from horizontal cells in isolated fish retinae sometimes
      reveal that the cells are hyperpolarized in darkness and that their responses to
      light stimulation are reduced or completely suppressed [11,15]. At cessation of
      stimulation, however, the cells respond with a transient surge of depolarization.
      Data relating to this phenomenon are presented and analyzed in terms of
      Trifonov's [17] model for neurotransmission between retinal photoreceptors and
      horizontal cells. Good quantitative prediction of the experimental data can be
      obtained by using the relation between concentration of neurotransmitter and
      postreceptoral voltage response found for the electroplax membrane of the torpedo
      eel [4].

PMID- 19604777
TI  - Prolonged activation of soleus motoneurones following a conditioning train in
      soleus Ia afferents - A case for a reverberating loop?
AB  - In the decerebrate cat a short train of impulses in Ia afferents from the soleus
      muscle (or its synergists) may cause a long latency prolonged activity in the
      soleus muscle as judged by EMG and tension recording. The excitability increase
      may stay virtually constant during long periods (several minutes) but can be
      terminated at any time by a train of impulses in, for example, the peroneal
      nerve. It is suggested that the conditioning Ia impulses activate a neuronal
      circuit which can maintain a reverberating activity thereby causing the
      heightened excitability of the soleus motoneurones.

PMID- 19604778
TI  - Changes in protein content of developing brain synaptic membranes, mitochondria
      and myelin.
AB  - The development of myelin, synaptosomal plasma membranes (SPM) and mitochondria
      in neonatal rat cortex has been followed by examining the electrophoretic
      profiles of protein in brain subcellular fractions. The appearance of the myelin
      proteins parallels the time course of myelination and confirms previous reports
      of the order of appearance of the proteins. Few changes occur in mitochondria
      during the developmental period. Plasma membranes in the SPM fraction show a
      progressive change from an ante-synaptogenesis profile to that characteristic of
      adult SPM. Tubulin, which is the major synaptic junctional protein, reaches its
      adult level in the developing SPM earlier than other SPM proteins, indicating
      that it may be involved in establishing the basic framework of the junction.

PMID- 19604779
TI  - The effect of glucose on the activity of the adrenal nerve and pancreatic branch
      of the vagus nerve in the rabbit.
AB  - Efferent discharges were recorded from nerve filaments dissected from the adrenal
      branch of the splanchnic nerve and pancreatic branch of the vagus nerve. Infusion
      of glucose into the carotid artery caused a decrease in discharge rate of adrenal
      nerve and an increase of it in the pancreatic branch of the vagus nerve. No
      change in activity in both nerve branches was observed following infusion of
      mannose. An i.v. injection of glucose showed smaller effects. Glucose-sensitive
      neurons in the hypothalamus may play a role in these responses.

PMID- 19604780
TI  - Mode of action of a sympathomimetic amine, paramethoxyphenylethylamine (PMPEA) in
      the mouse CNS: Release of biogenic amines.
AB  - Paramethoxyphenylethylamine (PMPEA) is a sympathomimetic amine, like its parent
      compound, phenylethylamine. The intraperitoneal administration of PMPEA to mice
      produces a dose-dependent depletion of brain and heart norepinephrine, with
      significant reduction being observed one hour postinjection. At lower dosages,
      PMPEA produces a transitory increase in brain serotonin (5-HT) levels, with
      depletion observed at the higher dosage used. Thus PMPEA differs from
      phenylethylamine, which does not deplete 5-HT. The results are interpreted that:
      the behavioral and neurophysiological effects of PMPEA may be related in part to
      the effects of this amine on serotonergic systems as well as to its effects on
      monoaminergic systems.

PMID- 19604781
TI  - Methylmercury induced neuromuscular dysfunction in the rat.
AB  - Rats were exposed to 20 mg/kg methylmercury for 10-18 days. The isolated phrenic
      nerve-hemidiaphragms from these animals demonstrated a reduced capability to
      maintain contraction amplitude when stimulated at a frequency of 10/sec. The
      addition of neostigmine directly to the organ bath produced a contraction
      enhancement significantly lower than normal. In a different series of isolated
      preparations, it was demonstrated that methylmercury at a final bath
      concentration of 2 x 10(-5) M could inhibit contractions completely with only a
      small degree of recovery. The muscles still responded to direct stimulation and
      nerve action potentials appeared unchanged. These observations may account for
      the muscular weakness in methylmercury intoxicated rats.

PMID- 19604782
TI  - Effect of prior experience of an environment on scopolamine-induced changes in
      activity.
AB  - Rats were given 0 or 30 min prior experience of a 36 in. x 36 in. open field then
      injected with saline or 0.25 or 4.0 mg/kg scopolamine before being tested in the
      field for 15 min. With no prior experience both doses of scopolamine produced
      equivalent increases in ambulation and 4.0 mg/kg increased rearing but neither
      dose affected grooming; however, with experience scopolamine increased ambulation
      and rearing in a dose-related way and produced equivalent increases in grooming.
      The resulting level of ambulation and rearing produced by 4.0 mg/kg was, however,
      higher and that of 0.25 mg/kg lower (for ambulation) in the experience condition
      compared to that in the no experience condition. These effects could partly be
      attributed to a decreased level of each response in the undrugged animals in the
      experience condition. It was concluded that prior experience of an environment
      does change scopolamine-induced effects on activity.

PMID- 19604783
TI  - Differential effects on self-stimulation and motor behaviour produced by
      microintracranial injections of a dopamine-receptor blocking agent.
AB  - Intraperitoneal injections of a dopamine-receptor blocking agent, spiroperidol,
      equally and severely attenuated self-stimulation in two groups of rats which
      either performed the motor task of licking a tube or performed the more complex
      task of pressing a bar in order to obtain stimulation in the lateral
      hypothalamus. Unilateral microinjections of 9 mug of spiroperidol into the
      nucleus accumbens attenuated self-stimulation without producing an apparent
      impairment of motor behaviour. The same injections into the corpus striatum
      produced an impairment of motor behaviour but self-stimulation was almost
      unaffected. The effect of spiroperidol on self-stimulation can therefore be
      dissociated from the effect on motor behaviour. These results suggests that
      dopamine receptors are involved in self-stimulation independently of their role
      in motor behaviour.

PMID- 19604785
TI  - Netherlands Central Institute for brain research?

PMID- 19604784
TI  - Growth hormone response to D-amphetamine in normal controls and in depressive
      patients.
AB  - This study introduces amphetamine as a stimulus for growth hormone release in
      man. d-amphetamine sulfate (0.1 mg/kg body weight) was slowly administered
      intravenously to 21 normals, nine endogenous depressives and seven neurotic
      depressives. The human growth hormone (HGH) response was measured. Endogenous
      depressives show a significantly lower (P = 0.01) response to d-amphetamine
      sulfate than normal controls. By contrast, neurotic depressives show a
      significantly higher HGH response (P < 0.05) than normals. Considering the
      pharmacological properties of amphetamine, our findings are compatible with the
      hypothesis that a disturbance of brain aminergic systems represents one
      biological correlate of depressive illness.

PMID- 19604786
TI  - Ultrastructural observations on branching patterns of central axons.

PMID- 19604787
TI  - Pericruciate cortical neurons projecting to brain stem reticular formation,
      dorsal column nuclei and spinal cord in the cat.

PMID- 19604788
TI  - Amygdalotegmental projections in the rat, cat and rhesus monkey.

PMID- 19604789
TI  - Evidence for a loss of afferent axons in the visual cortex of monocularly
      deprived cats.

PMID- 19604790
TI  - Topography and bioelectrical properties of identifiable neurons in the buccal
      ganglion of Helix pomatia.

PMID- 19604791
TI  - Effects of methergoline on central monoamine neurones. Evidence for a selective
      blockade of central 5-HT receptors.

PMID- 19604793
TI  - Interpretation of cells in the wall of the telencephalic vesicle.

PMID- 19604792
TI  - Effects of transecting the lateral border of the hypothalamus on self
      stimulation.

PMID- 19604794
TI  - The role of climbing fibers in the development of Purkinje cell dendrites.
AB  - Destruction of the inferior olivary nucleus was performed in newborn kittens in
      order to study the role of climbing fibers in the postnatal development of the
      cerebellum. In the three kittens which survived for 40-45 days after the
      unilateral destruction at 2 days old, histological examination demonstrated the
      lack of dendritic arborization in many Purkinje cells in the cerebellar cortex
      contralateral to the lesion. The olivectomized kittens showed cerebellar symptoms
      which became conspicuous when the kittens started to walk. The results reveal an
      important role of climbing fibers in the development of Purkinje cell dendrites.

PMID- 19604795
TI  - The fine structural demonstration of monoaminergic synapses in immature rat
      neocortex.
AB  - The radial distribution of monoaminergic (MA) synapses has been studied in
      lateral neocortex (SI) of infant rats using an electron microscopic histochemical
      technique. Systemically administered 5-hydroxydopamine crosses the blood-brain
      barrier and produces small granular vesicles (SGV) in 30% of all synaptic
      terminals in SI. In the primordium of layer IV, at six days postnatal, 70% of the
      synaptic terminals contain SGVs. Immature cortex thus contains a high proportion
      of synapses with a vesicular uptake-storage mechanism for catecholamines. It is
      proposed that in infant rat there is a major projection from brain stem MA nuclei
      to the neocortex; this projection may exert a potent influence on the activity of
      neurons in layer IV.

PMID- 19604796
TI  - A fast propriospinal inhibitory pathway from forelimb afferents to motoneurones
      of hindlimb flexor digitorum longus.
AB  - In high spinalized cats the propriospinal effects of forelimb afferents upon 145
      motoneurones of seven different flexor and extensor hindlimb muscles were
      investigated with intracellular recording. All types of motoneurones showed late
      (latency longer than 6 msec) excitatory or mixed excitatory-inhibitory effects to
      forelimb nerve stimulation. Only in flexor digitorum and hallucis longus (FDL)
      motoneurones were distinct effects with shorter latencies observed, which,
      however, were exclusively inhibitory. The IPSPs were evoked from cutaneous and
      muscle afferents and had a minimal central latency of 3.1 msec. They were
      probably mediated via a trisynaptic pathway.

PMID- 19604797
TI  - Development of binaural responses in the kitten inferior colliculus.
AB  - The incidence and nature of binaural responses were determined for 174 units in
      the inferior colliculus of 16 anaesthetized kittens aged between 5 and 35 days.
      As early as the first week of life a majority of units is influenced by binaural
      stimuli, and in this and subsequent weeks of life the forms of binaural
      interaction characteristics of the adult may be recognized. Best frequencies for
      given units excited by stimuli applied to either ear were very similar. The
      results indicate that binaural connections may be established at or before the
      onset of hearing in the cat.

PMID- 19604798
TI  - Quantitative measures of the thermal reactivity of cutaneous mechanoreceptors.
AB  - Quantitative aspects of the non-specific response of cutaneous mechanoreceptors
      to two different modalities of stimulation were examined. Parameterization of
      stimulus temperature reveals the incompleteness of the commonly accepted
      criterion for thermal sensitivity and suggests the need for a re-examination of
      current concepts of specific mechanical, thermal and nociceptive sensibility.

PMID- 19604799
TI  - The influence of pineal activation, removal or denervation on hypothalamic
      luteinizing hormone-releasing hormone activity: an in vitro study.
AB  - Female rats between 23 and 25 days of age were left intact or rendered either
      blind-anosmic, blind-anosmic-pinealectomized, blind-anosmic-superior cervical
      ganglionectomized or blind-anosmic-nervi conarii transected. Five weeks later the
      medial basal hypothalamic luteinizing hormone-releasing hormone (LRH) activity of
      each group of animals was assessed in vitro. The medial basal hypothalamic LRH
      activity in the blind-anosmic animals was greater than that of the intact rats.
      Pinealectomy, superior cervical ganglionectomy and nervi conarii transection were
      equally effective in reversing the effects of blinding and anosmia on LRH
      activity.

PMID- 19604800
TI  - Susceptibility to startle during ongoing behaviour following collicular lesions
      in the rat.
AB  - Normal rats tend to respond to a sudden burst of noise or flash of light with
      slightly less startle when they are engaged in active behaviour at the time of
      presentation. This effect is vastly more pronounced in animals with lesions of
      the superior colliculus. These results are taken as support for a theory
      implicating this midbrain structure in the process of redirecting attention.

PMID- 19604801
TI  - Influence of 6-hydroxydopamine injections in the substantia nigra on lateral
      hypothalamic reinforcement.
AB  - Repeated unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia
      nigra of rats caused massive non-specific lesions and disrupted self-stimulation
      by lever-pressing equally from electrodes in the ipsilateral and contralateral
      hypothalamus. Repeated bilateral injections of 6-OHDA abolished self-stimulation
      when lever-pressing was the criteria, but not when simpler motor responses were
      used as operants. Hence, nigrostriatal dopamine is unlikely to be critically
      involved in operant learning and reward processes.

PMID- 19604802
TI  - Attenuation of amphetamine-induced conditioned taste aversion following
      intraventricular 6-hydroxydopamine.
AB  - Intraventricular administration of 6-hydroxydopamine, which depleted central
      norepinephrine and dopamine contents to 17 and 10% of control levels,
      respectively, was shown to severely attenuate a conditioned taste aversion
      induced by repeated exposure to 1.0 mg/kg d-amphetamine. This attenuation was not
      the result of a general learning deficit because animals with identical
      treatments acquired a conditioned taste aversion when lithium chloride was used
      as the punishing stimulus. These and other [5,6] results suggest that the
      punishing, as well as the rewarding properties of amphetamine are mediated via
      central catecholaminergic neurons.

PMID- 19604803
TI  - Letter to the editor.

PMID- 19604804
TI  - Barreloids in mouse somatosensory thalamus.
AB  - In the mouse, in the medial part of the ventrobasal complex of the thalamus
      (VBm), an array of rod-shaped domains, poor in perikarya and with a diameter of
      about 70 microm, is embedded in a lattice of high cell packing-density. Each
      domain forms the core of a 'barreloid'. The arrangement of barreloids is
      topologically equivalent to that of the large barrels in the cortical
      somatosensory area (SI).

PMID- 19604805
TI  - Projections of reticular neurones to dorsal regions of the spinal cord in the
      cat.
AB  - Reticulospinal neurones in the cat were identified by extracellular recording and
      antidromic stimulation of their axons in the cord. Approximately 34% of
      reticulospinal neurones in the medulla, and 28% in the pons, were found to
      project to dorsal regions of the cord, between T9 and L2. Most of these neurones
      had one branch situated dorsally and another in the ventral or ventrolateral
      funiculus. Some branches travelled for short distances in the dorsal columns.
      Microstimulation techniques demonstrated the presence of branches of
      reticulospinal fibres in the dorsal horn. The results may provide an anatomical
      basis for the widespread effects of stimulation of the reticular formation on
      afferent transmission in the spinal cord.

PMID- 19604806
TI  - Independence of sleep-wakefulness cycle in an implanted head 'encephale isole'.
AB  - A quantitative study was carried out on the sleep-wakefulness cycle by means of
      EEG recordings taken simultaneously from a dog's implanted head and its host.
      During survival (108 h), neurological activities of the implanted head were
      similar to those of classic 'encephale isole' preparations. In spite of a common
      circulation, the sleep-wakefulness cycles of the implanted head and host animal
      were independent. Independence was manifested by: (1) differing percentages of
      respective phases of their cycles; (2) periods of coincident phases in both
      heads, only occasionally beginning and/or stopping simultaneously; and (3) the
      implanted 'encephale isole' showed a monotonous cycle with numerous periods of
      short duration throughout night or day. The host presented a nycthemeral rhythm.

PMID- 19604807
TI  - Localization of corticotropin-releasing activity in the rat hypothalamus.
AB  - Hypothalamic nuclei were removed from frozen sections of rat brain and examined
      for their corticotropin-releasing activity. The highest concentration was
      measured in the median eminence. In addition there was significantly more
      activity detected in the nuclei paraventricularis, supraopticus,
      suprachiasmaticus and arcuatus than in the other nuclei.

PMID- 19604808
TI  - Effect of the S-100 protein on the RNA-polymerase activity in brain nucleoli
      isolated from newborn rat.
AB  - The structural integrity of the nucleus is not a prerequisite for the action of
      the S-100 protein on the RNA-polymerase activity in brain nuclei. In fact the
      protein also stimulates the enzyme activity in sonicated nuclei of newborn rat,
      as well as directly in isolated nucleoli from the same source.

PMID- 19604809
TI  - Inhibition of the noradrenergic induction of pineal N-acetyltransferase by
      dibutyryl cyclic guanosine monophosphate and by ionophore X-537A.
AB  - Utilizing rat pineals in vitro, it can be demonstrated that dibutyryl cyclic GMP
      and the calcium ionophore X-537A are both able to reversibly inhibit the
      elevation of pineal N-acetyltransferase induced by the beta-agonists
      norepinephrine or isoproterenol. These results are discussed in terms of the
      known hyposensitivy of the pineal gland to overstimulation by beta-agonists.

PMID- 19604810
TI  - Effects of high dose propranolol treatment on dopamine and norepinephrine
      metabolism in regions of rat brain.
AB  - The acute effects of a high dose of d,l-propranolol on the levels of homovanillic
      acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 4-hydroxy-3
      methoxyphenylethylene glycol (HMPG) in rat brain regions were determined by mass
      fragmentography. A significant elevation of HVA was obtained in the olfactory
      tubercle but not in the striatum. The level of 5-HIAA was unchanged in both these
      regions. The level of HMPG was significantly elevated in the rest of the brain.
      The roles of dopamine and norepinephrine neurons and their interaction for the
      possible effects of propranolol in psychosis are discussed.

PMID- 19604811
TI  - Differential involvement of cholinergic mechanisms in activity and sociability in
      rats.
AB  - Four groups of six rats, injected with saline, 0.1, 0.25 or 1.0 mg/kg
      scopolamine, were tested in a 36 x 36 in. open field for 10 min. Scopolamine
      differentially affected ambulation, rearing, social contacts and the social and
      perimeter distances between rats; and increased corner preference. This
      experiment shows that several component responses of activity and sociability
      need to be recorded if a better understanding of the involvement of cholinergic
      mechanisms in behaviour is to be obtained.

PMID- 19604812
TI  - Spontaneous occurrence of spastic paresis in Han-Wistar rats.
AB  - The occurrence of spastic paresis and paralysis in rats of the Han: WIST strain
      is described. The results of this study indicate that this neural disorder starts
      with progressive development at the age of about 4-5 weeks independent of the
      sex. At this time the affected animals are significantly smaller than the normal
      ones. The disease has been found to be due to an autosomal recessive gene.
      Electromyographic studies showed spontaneous discharges of tonic firing motor
      units.

PMID- 19604814
TI  - Golgi-stained barrel-neurons in the somatosensory region of the mouse cerebral
      cortex.

PMID- 19604815
TI  - Inquiry about a long-lasting, local anaesthetic.

PMID- 19604813
TI  - Injection of horseradish peroxidase solution in calibrated volumes (nanolitre)
      into the spinal cord.
AB  - A method for the injection of horseradish peroxidase (HRP) into the spinal cord
      (SC) is described, based on the principle of fluid expansion upon application of
      heat. HRP solution in the tip of a glass micropipette (tip diameter 10-15 microm)
      was extruded when the sealed stem of the pipette, containing distilled water, was
      warmed. The pipette was calibrated (temperature/volume relation) before it was
      inserted into the SC and the injection of HRP was made according to the
      calibration curve. Using the pipette as an electrode it was possible to locate
      its tip with reference to recorded field potentials. After the injection, the
      volume of HRP solution actually injected was determined.

PMID- 19604816
TI  - Projections to gyrus sigmoideus from the substantia nigra in the cat, as revealed
      by the horseradish peroxidase retrograde transport technique.
AB  - After injections of horseradish peroxidase in the gyrus sigmoideus of the cat
      frontal cortex, labelled neurones were found in the substantia nigra and the
      ventral tegmental area of Tsai. Neurones distributed bilaterally clearly
      predominated in the side of the injection in the rostral sections, but
      differences in number were less at caudal levels. The present findings confirm
      the existence of a direct mesencephalocortical projection from this ventral
      tegmental region, and provide a morphological substrate for a better
      understanding of the role of the dopaminergic systems in the motor cortical
      regulation.

PMID- 19604817
TI  - The dense core of vertebrate central nervous system synapses revealed by
      potassium permanganate fixation as formed by small membrane-bounded vesicles.
AB  - Large dense core vesicles occur in small number in the company of clear synaptic
      vesicles in various parts of the central nervous system following osmium or
      aldehydes fixation. When fixed by potassium permanganate large vesicles occur
      that contain one or more membrane-bounded small spherical vesicles, as is
      demonstrated in the habenular nuclei of the frog Rana esculenta. On a
      morphological basis we suppose that the population of this kind of synapse
      consists of the same type of vesicles, the majority being free while some are
      enclosed within a larger vesicle. An hypothesis on the meaning of these composite
      vesicles is presented.

PMID- 19604818
TI  - A combined cell column superfusion technique to study hypothalamus-pituitary
      adrenal interactions in vitro.
AB  - Rat anterior pituitaries and rat adrenals were dispersed into cell suspensions.
      In a cell column superfusion system the pituitary cells were used to study ACTH
      release and the adrenal cells served as a means to detect that hormone. Linear
      log-dose-response relationships were exhibited by the adrenal cells for ACTH and
      by the pituitary cell-adrenal cell system for corticotropin-releasing factor
      (CRF). A combined system, constructed of a superfused hypothalamus, leading into
      a column of pituitary cells which was connected to a column of adrenal cells, was
      used to study the characteristics of CRF release from the hypothalamic block.
      Basal and stimulated CRF release were both Ca(2+)-dependent.

PMID- 19604819
TI  - Effect of estrogen of early postnatal development of synaptic formation in the
      hypothalamic arcuate nucleus of female rats.
AB  - Female rats were given injections of estradiol benzoate for the first 30 days of
      their postnatal life; i.e., 2 microg for the first 10 days and 4 microg and 8
      microg for the middle and last 10 days, respectively. On the day following the
      last injection (31 days of age), the hypothalamic arcuate nucleus (ARCN) was
      examined ultrastructurally and the axodendritic and axosomatic synapses were
      counted in a field of 10,117.5 microm(2) in the middle part of the ARCN. The mean
      number of axodendritic synapses in the ARCN of the neonatally estrogenized
      females was about two-fold greater than that of oil-treated controls. As for the
      number of axosomatic synapses, of which incidence was low, there was no
      significant difference between the estrogenized and control animals. From these
      results it is suggested that an increase in the number of axodendritic synapses
      in the ARCN is caused by neonatal treatment with estrogen.

PMID- 19604820
TI  - Factors in cerebrospinal fluid affecting motor activity in the rat.
AB  - Cerebrospinal fluid (CSF) was obtained from donor rats either during the dark or
      during the light period of their diurnal cycle, and infused into the lateral
      ventricle of recipient rats. Infusing recipient rats during their dark period
      with CSF from light-exposed donors reduced the motor activity, whereas,
      conversely, infusing them during their light period with CSF from dark-exposed
      rats increased the motor activity. Humoral factors may serve to regulate the
      level of motor activity and vigilance.

PMID- 19604821
TI  - Direct evidence for the stimulation of rabbit retina dopamine receptors by ergot
      alkaloids.
AB  - The effects of three ergot alkaloids on cyclic AMP concentrations in isolated
      retinae of the rabbit were investigated. Significant increases in cyclic AMP
      concentration were found after a 10 min exposure to 1 microM ergometrine or
      agroclavine. The increases in cyclic AMP elicited by ergometrine, agroclavine or
      2-bromo-alpha-ergocryptine (CB-154), at 100 microM concentrations, were
      comparable to those seen after dopamine or the dopamine-like drug, apomorphine.
      Furthermore, the effects of the ergot alkaloids were blocked by the specific
      dopamine receptor blocking agent, fluphenazine. It is concluded that some ergot
      alkaloids or their derivatives are potential dopamine-mimetic drugs.

PMID- 19604822
TI  - Role of membrane depolarization in transsynaptic induction of tyrosine
      hydroxylase in organ cultures of sympathetic ganglia.
AB  - In contrast to nicotinic cholinomimetics which generate action potentials in
      postganglionic adrenergic neurons, general non-specific depolarizing agents such
      as veratridine and batrachotoxin (which also generate action potentials) do not
      initiate tyrosine hydroxylase (TH) induction. Moreover, tetrodotoxin, a selective
      blocker of fast sodium channels, which prevents the formation of action
      potentials, does not interfere with TH induction mediated by carbamylcholine or
      nicotine. It is concluded that specific TH induction is mediated via nicotinic
      receptors by a mechanism which is not dependent on the activation of the fast
      sodium channels.

PMID- 19604823
TI  - "In vitro" studies on the fate of diphenylhydantoin in uremia.
AB  - "In vitro" studies were undertaken to evaluate the fate of DPH in blood of uremic
      patients. DPH incubated for 18 h at 37 degrees C disappears from plasma in the
      presence of erythrocytes and more when the blood underwent hemolysis. This
      phenomenon was more pronounced in uremic blood. These findings suggest not only
      that DPH is absorbed onto the erythrocyte membrane, but also that it is bound by
      erythrocyte contents. It could be possible that, because of a low binding
      capacity of the albumin carrier in uremic blood, the drug penetrates more easily
      the erythrocyte membrane and is bound there. An intraery throcyte enzymatic
      metabolism of DPH is not excluded.

PMID- 19604824
TI  - Elevated erythrocyte phospholipase A associated with Duchenne and myotonic
      muscular dystrophy.
AB  - Erythrocytes from patients with Duchenne or myotonic muscular dystrophy exhibit
      substantially increased phospholipase A activity when compared to those from
      normal subjects. Incubation of dystrophic erythrocyte membranes with
      diphenylhydantoin lowers the phospholipase A activity to within normal limits
      while the drug does not diminish activity in membranes from normal cells.
      Elevated phospholipase A activity may be expected to lead to increased
      concentrations of lysophospholipids which may contribute to the membrane
      dysfunction shown to be associated with these diseases.

PMID- 19604825
TI  - Ganglioside syndrome, a new autoimmune neurologic disorder, experimentally
      induced with brain gangliosides.
AB  - Rabbits intensively immunized with total bovine brain gangliosides or a certain
      molecular species of gangliosides, such as GD(1a) and GM(1), respectively, in
      complete Freud's adjuvant developed a variety of neurologic symptoms and signs
      which closely resembled experimental allergic encephalomyelitis, i.e., a sluggish
      righting reflex, muscular weakness, hindleg paralysis (flaccid in the case of
      GD(1a) and rigid in GM(1)) and body weight loss, frequently followed by death.
      Histological examinations of GD(1a)-immunized rabbits showed extensive
      degeneration of the peripheral nerves, including breakdown of myelin and
      fragmentation of axis cylinders. In central nervous tissues, however, only mild
      damage was observed in some cases. Similar neurologic symptoms and signs were
      also induced in guinea pigs. The results suggest that this syndrome might be
      induced by a cell-mediated autoimmune response to gangliosides.

PMID- 19604826
TI  - Does apomorphine affect the GABA turnover in the DA cell group rich area of the
      mesencephalon?

PMID- 19604827
TI  - Central and peripheral neurite growth patterns in tissue culture.
AB  - Neurites of mesencephalic V nucleus neurons, which in vivo have a peripheral
      process, were observed to grow away from cerebellar explants. This pattern of
      neurite growth was contrasted with a previously observed pattern of looping and
      returning to the explant characteristic of central processes of other neurons in
      cerebellar cultures. The described tissue culture system could serve as a model
      for elucidating mechanisms which determine the directional growth of neurites.

PMID- 19604828
TI  - Nerve endings on the intramuscular tendons of cat extraocular muscles.
AB  - The extraocular muscles of the cat have been studied with silver-impregnated,
      teased preparations. Short and long muscle fibers have been found among the multi
      innervated as well as among the focally-innervated muscle fibers. The attachments
      between the short fibers are made by intramuscular tendons. Longer fibers may
      have myomyal bridges. A peculiar kind of nerve ending has been found on the
      intramuscular tendons of short multi-innervated fibers. These endings are
      supplied by myelinated axons which also give endings to the muscle fibers. The
      significance of these nerve endings is discussed.

PMID- 19604829
TI  - Synaptic structure of the lateral line lobe nucleus in mormyrid fish.
AB  - Electron microscopical observations reveal a complex synaptic structure (Fig. 1)
      in the nucleus of the lateral line lobe (nLLL). Different types of axosomatic and
      axoaxonic synapses are demonstrated to be in contact with the large cells. The
      results furnish morphological evidence for electrotonic transmission (by way of
      club endings with gap junctions) at this level of the electrosensory pathway of
      mormyrid fish. A new ultrastructural finding is the existence of presynaptic gap
      junctions on the unmyelinated surface area of the club endings.

PMID- 19604830
TI  - Fast conducting electrosensory pathway in the mormyrid fish, Gnathonemus
      petersii.
AB  - A compound action potential of short latency was recorded from the ganglion
      mesencephali extrolaterale in response to both the fish's own electric organ
      discharge and electric stimulation of the whole fish or a branch of the posterior
      lateral line nerve. The time difference between the response in the nerve, 16 mm
      from its entry into the brain, and the mesencephalic ganglion, which is
      positioned 10 mm anterior in the CNS, was found to be 1.6 msec. This rapid
      conduction pathway involves peripheral nerve fibres of high conduction velocity
      (40 m/sec) and presumably two electric synapses, one at the rhombencephalic and
      the other at the mesencephalic level.

PMID- 19604831
TI  - Ultrastructural observations in the frog spinal cord in relation to the
      generation of primary afferent depolarization.
AB  - The spatial distribution of different types of synaptic boutons over the
      motoneuron cell body and dendrites was studied both in the normal and in the
      chronically deafferented frog spinal cord. In both preparations, endings with S
      type (spherical) vesicles were more numerous than those with F (flat) vesicles,
      the S F synapse ratio being approximately constant when measured at the soma, the
      proximal dendrites or the fine dendrites. However, the proportion of S boutons,
      as well as the proportion of degenerated boutons of afferent fibers in close
      apposition with other boutons, was higher on the fine dendrites in the lateral
      neuropile than on the motoneuron cell body and proximal dendrites, and in all
      cases significantly higher than the proportion of F boutons showing close
      appositions with other boutons. Degenerated boutons from descending fibers were
      found to synapse over the motoneuron cell body and proximal dendrites, but these
      boutons were rarely seen to be closely apposed to other boutons. The possible
      relation of these findings to the mechanisms generating primary afferent
      depolarization is discussed.

PMID- 19604832
TI  - Extracellular potassium concentration and focal electrical potentials elicited in
      the cerebral cortex of rat by interhemispheric stimulation.
AB  - All points in the time course of the evoked and self-sustained, DC-recorded
      potentials elicited by repetitive interhemispheric stimulation were found to
      remain negative by -1 mV and more with respect to the prestimulation DC level
      only when the coinciding, directly recorded, extracellular potassium
      concentration was 11 mM. A slow oscilloscope sweep displayed the -1 mV level as a
      virtual line limiting the initial positive waves of the interhemispheric
      response. This line, approximately parallel with the potassium concentration
      record of around 11 mM, probably expresses the potassium-dependent membrane
      depolarizations, which were not revealed at lower potassium concentrations. The
      evoked and self-sustained potentials coinciding with the latter were displayed in
      negative as well as positive values.

PMID- 19604833
TI  - The RNA of chick forebrain synaptosomes.
AB  - The RNA species present in myelin, synaptosomal, mitochondrial, microsomal and
      post-microsomal fractions obtained from chick forebrain have been investigated
      using polyacrylamide gels. The primary species associated with the synaptosomal
      fraction are the 28S, 18S and 5S rRNAs, in addition to species L and 4S tRNA. No
      detectable mitochondrial rRNA has been found. The significance of these results
      is discussed in relation to the study of synaptosomal protein synthesis.

PMID- 19604834
TI  - Opiate antagonists suppress ACTH(1-24)-induced excessive grooming in the rat.
AB  - Intraventricular injection of ACTH(1-24) in rats induces excessive grooming
      behavior, and subsequent peripheral administration of specific opiate antagonists
      suppresses this peptide-induced grooming response. Intraventricular injection of
      morphine mimics both in intact and hypophysectomized rats' - to a certain extent 
      peptide-induced grooming. The results suggest similarities in the interaction of
      morphine and ACTH(1-24) with central nervous structures.

PMID- 19604835
TI  - Memory formation: a new three-phase model.
AB  - A new three-phase pharmacological model of memory formation is proposed: (i) a
      short-term memory phase lasting 10 min, inhibited by lithium chloride (LiCl) and
      potassium chloride (KCl), but not by ouabain; (ii) a labile, sodium pump
      dependent phase occurring after 10 min, inhibited by ouabain but not by
      cycloheximide (CXM); and (iii) a permanent, protein synthesis-dependent phase
      occurring after 30 min and inhibited by CXM. Diphenylhydantoin (DPH), which
      stimulates Na(+)-K(+)-ATPase activity, overcomes ouabain- and CXM-induced amnesia
      but not LiCl- or KCl-induced amnesia.

PMID- 19604836
TI  - Plasma gangliosides in multiple sclerosis.
AB  - The total concentration and the relative distribution of gangliosides isolated
      from plasma of patients with multiple sclerosis (MS) and controls were
      determined. The fatty acid and hexose constituents of GM(3) were also determined.
      GM(3) was found to be the major plasma ganglioside in both the MS and control
      groups. The total plasma ganglioside concentration, expressed as N
      acetylneuraminic acid (sialic acid), was significantly lower in the MS group than
      in the control group. No difference was observed in the various ganglioside
      fractions between the two groups. Analyses by gas-liquid chromatography of the
      relative per cent composition of the fatty acids of the GM(3)-gangliosides
      revealed no significant differences between the two groups. Analyses of the
      hexose moieties of the GM(3)-gangliosides of the MS group revealed the presence
      of only glucose and galactose in a 1:1 ratio.

PMID- 19604837
TI  - Continuous mapping of direction selectivity in the cat's visual cortex.
AB  - A new method is demonstrated for continuously mapping direction selectivity on
      complex cells in the cat's visual cortex. A large area random noise pattern which
      always covers the whole receptive field area is moved along a circular path. The
      average response histogram yields the cell's selectivity for stimulus direction
      directly and in much less time than the conventional methods.

PMID- 19604838
TI  - Post-trial reinforcing hypothalamic stimulation can facilitate avoidance
      learning.
AB  - Thirty seconds (0.2 sec on, 0.8 sec off) reinforcing electrical stimulation of
      the lateral hypothalamus of rats (presented 30 sec after the trial) facilitated
      learning of an avoidance task. This result was interpreted in terms of a direct
      influence of reinforcement on short-term memory processes.

PMID- 19604839
TI  - Changes in duodenal motility produced by noxious mechanical stimulation of the
      skin in rats.
AB  - Three major pressure components were recorded in the duodenum of anesthetized
      rats by the balloon method: (1) small, fast, rhythmic waves which corresponded to
      the pendular movement of the duodenum; (2) large, slow, rhythmic waves which
      corresponded to the peristaltic movement; (3) the baseline component of the
      pressure. Noxious stimulation was applied to the skin of the neck, chest and
      abdomen, but only abdominal stimulation produced changes in duodenal pressure.
      The following three reflexes were observed whose efferent pathways were proven to
      be through sympathetic nerves and whose major pathway was apparently
      propriospinal: (1) a decrease in the amplitude of the small, fast, rhythmic
      waves; (2) a decrease in frequency of the large, slow, rhythmic waves; (3) a
      decrease in baseline of duodenal pressure.

PMID- 19604840
TI  - Recording of dorsal raphe unit activity in vitro.
AB  - The spontaneous electrical activity of single neurons of the midbrain dorsal
      raphe nucleus in the rat was recorded in vitro in 400 mum thick slices. The
      majority of raphe neurons exhibited the slow and regular discharge pattern that
      characterizes the activity of raphe neurons when recorded in vivo. The viability
      of these neurons in vitro thus provides a preparation for analyzing endogenous
      and exogenous factors that regulate the activity of these serotonin-containing
      neurons.

PMID- 19604841
TI  - Characterization and topography of LH-RH neurons in the rabbit.
AB  - The localization of luteinizing hormone-releasing hormone (LH-RH) has been
      studied in the rabbit with the indirect immunofluorescence technique. LH-RH
      positive perikarya are scattered from the rostral mesencephalon up to the
      parolfactory area and give rise to two main tracts ending in the infundibulum and
      the lamina terminalis.

PMID- 19604843
TI  - Neurotrophic effects: Axoplasmic transport involvement in the regulation of
      skeletal muscle soluble proteins.
AB  - Skeletal muscle soluble proteins were assayed by polyacrylamide gel disc
      electrophoresis at different times (4-36 days) after injection of 10 mM
      colchicine into the motor nerve and after denervation. Results showed that
      effects of drug-induced axoplasmic transport blockage differ from those of
      denervation as to quantitative changes in the protein concentration of certain
      bands. Results point to the conclusion that axoplasmic transport is involved in
      the neural control of a number of muscle proteins. This does not invalidate the
      participation of acetylcholine and muscle activity in the regulation of muscle
      metabolism.

PMID- 19604842
TI  - Pineal effects upon pituitary protein and nucleic acid synthesis in vitro.
AB  - The effects of various dilutions of pineal extract upon leucine and thymidine
      incorporation by pituitary cells were studied in vitro, using a miniature cell
      culture system. A pineal extract dose-dependent increase in thymidine and leucine
      incorporation by these pituitary cells was observed. These effects may be related
      to either increased synthesis and/or decreased secretion of newly synthesized
      proteins.

PMID- 19604844
TI  - Actin-like filaments in synaptosomes detected by heavy meromyosin binding.
AB  - We have prepared cat forebrain synaptosomes in order to investigate the presence
      of actin-like proteins. First, actin-like filaments were demonstrated using a
      heavy meromyosin binding technique. Decorated filaments form networks inside the
      synaptosomes and are frequently seen in relation to membranes and synaptic
      vesicles. Second, using SDS-polyacrylamide gel electrophoresis, a band
      corresponding to actin appears to be one of the major constituents of
      synaptosomal fractions; this confirms the work of Fine and his coworkers. The
      significance of actin-like filaments in relation to axoplasmic transport is
      briefly discussed.

PMID- 19604845
TI  - Action of amino acid transmitters on glial cells in tissue culture.
AB  - Intracellular recordings were made from glial cells of human and rat spinal cord
      grown in tissue culture. The membrane potentials of the glial cells were usually
      higher than those recorded from neurones. Addition of the putative
      neurotransmitters glycine, GABA, glutamate and aspartate to the bathing fluid in
      a concentration of 10(-4) M had no effect on the membrane potential of most glial
      cells tested.

PMID- 19604846
TI  - Immunohistochemical evidence for the existence of angiotensin II-containing nerve
      terminals in the brain and spinal cord in the rat.
AB  - Using the indirect immunohistochemical method it has been possible to demonstrate
      angiotensin II or angiotensin II-like immunoreactivity in probable axons and
      nerve terminals in the brain and spinal cord of normal rat, resistant to
      bilateral nephrectomy. A high density of angiotensin II-cotaining nerve terminals
      has been found in the substantia gelatinosa of the spinal cord and the medulla
      oblongata, suggesting a role of this peptide in the mediation of sensory
      information to the CNS. A high density was found in the sympathetic lateral
      column, which supports the view that this peptide is involved in central blood
      pressure control. A plexus of angiotensin II nerve terminals in the locus
      coeruleus may control activity in the coerulocortical noradrenergic pathways. The
      existence of a substantial innervation of the medial external layer of the median
      eminence may suggest a role of angiotensin II in anterior pituitary control as,
      for example, a hypothalamic hormone.

PMID- 19604847
TI  - In vitro protein synthesis by oligodendroglial cells.
AB  - Oligodendroglial cells were isolated from spinal cord and brain stem tissue from
      30-day-old rats according to the method of Poduslo and Norton except that
      acetylated trypsin at a concentration of 0.05% was used instead of unmodified
      trypsin, and the density gradient was slightly changed. Isolated oligodendroglial
      cells were found to incorporate [U-(14)C]leucine into TCA-insoluble protein up to
      120 min. This incorporation was inhibited by cycloheximide and chloramphenicol.
      Purity of the cell preparation was assessed by phase contrast microscopy and by
      assay of 2',3'-cyclic nucleotide phosphohydrolase activity.

PMID- 19604848
TI  - Further evidence that apomorphine increases GABA turnover in the DA cell body
      rich and DA nerve terminal rich areas of the brain.

PMID- 19604849
TI  - Neural agryrophilia induced by puromycin: A directed Golgi-like method.
AB  - Puromycin injected intracerebrally in rats renders affected neurons extremely
      argyrophilic, which makes it possible to demonstrate their fine geometry by the
      aid of a reduced silver impregnation procedure. The technique shows promise as a
      directed Golgi-like method. The abortive action of puromycin on protein synthesis
      produces a multitude of argyrophilic peptide fragments, which are subsequently
      transported throughout the neuron as protein-like moieties. It is hypothesized
      that these fragments serve as nucleation points for subsequent silver deposition.

PMID- 19604850
TI  - Combined light and electron microscopic tracing of neurons, including axons and
      synaptic terminals, after intracellular injection of horseradish peroxidase.
AB  - By using intracellular deposition of horseradish peroxidase (HRP), a method has
      been designed for combined light and electron microscopic tracing of single
      fibers and synaptic terminals, belonging to physiologically characterized
      neurons. This technique has been successfully tested on the axon collateral
      systems of cat alpha-motoneurons, but should also be applicable to other types of
      neurons.

PMID- 19604851
TI  - The absence of horseradish peroxidase uptake by cerebellar afferents to the red
      nucleus of the cat.
AB  - Horseradish peroxidase (HRP) administered to the red nucleus (RN) failed to be
      transported retrogradely in the axons of the cerebellorubral projection system.
      This negative result was independent of the anaesthesia, fixation method,
      injection time or survival period. The absence of HRP uptake and transport in our
      work reflects some uncertainty in the general usefulness of the HRP technique.

PMID- 19604852
TI  - Study of the early somatosympathetic reflex response.
AB  - Using anesthetized cats, we studied the early components of the somatosympathetic
      reflex in the white rami communicantes of segments T(3) and L(2) in response to
      stimulation of the corresponding segmental somatic nerves. The results show that
      the early somatosympathetic reflex is a complex and highly organized response
      consisting of three typical waves. The shortest latency wave of this reflex was
      investigated in detail and evidence of its monosynaptic nature was obtained.
      Calculations showed that the efferent part of this reflex component may be formed
      by sympathetic preganglionic neurons with axonal conduction velocities of about
      10 m/sec or more.

PMID- 19604853
TI  - Antidromic discharges of sympathetic preganglionic neurons located outside of the
      spinal cord lateral horns.
AB  - Responses arising in thin ventral rootlets and antidromic discharges of single
      sympathetic preganglionic neurons (SPNs) in T(3) and L(2) segments of the cat
      spinal cord were recorded simultaneously during stimulation of the white rami
      communicantes in the same segments. It was shown that in addition to the
      classical lateral horn SPN with B-axons (conduction velocities 3-10 m/sec) there
      are also ventral horn SPNs which have B-axons with faster conduction velocities
      (10-20 m/sec) and intermediate zone SPNs with C-axons (conduction velocities 0.98
      1.7 m/sec).

PMID- 19604854
TI  - Stimulation of peripheral ganglion cells in Helix pomatia L. by adenosine
      triphosphate.
AB  - The contractile activity of the penis retractor muscle (PRM) of Helix pomatia is
      controlled by both the central nervous system (CNS) and by a peripheral neural
      cell cluster. In the semi-intact PRM preparation, consisting of the PRM and the
      peripheral cell cluster without any attached central neuron, the CNS-mediated
      muscle activity was shown to be mimicked by exogenously applied adenosine
      triphosphate (ATP). This fact, coupled with the demonstration that ATP neither
      excites presynaptic motor nerve terminals nor postsynaptic sites at the
      neuromuscular junction, but exerts its action on the peripheral neural
      structures, may indicate a role of ATP in the neural transmission in the
      peripheral ganglionic mass at the base of the PRM.

PMID- 19604855
TI  - Patterns of electrocochleographic responses observed in the guinea pig during
      etacrynic acid intoxication.
AB  - During the disappearance and recovery of click-evoked cochlear nerve action
      potential following etacrynic acid intoxication in the guinea pig, the pattern of
      the electrocochleographic response reproduces the distorted patterns observed in
      human pathological situations such as Meniere's disorder, vascular disorder,
      vestibulocochlear schwannoma and kernicterus. These observations should help in
      finding a satisfactory interpretation of such human pathological patterns.

PMID- 19604856
TI  - Conditioned taste aversion induced by diethyldithiocarbamate (DDC).
AB  - Subcutaneous injections of 150, 300, or 600 mg/kg diethyldithiocarbamate (DDC)
      immediately following a 0.5 h exposure to a novel saccharin solution caused a
      pronounced aversion to saccharin in rats when tested four days later. No
      statistical difference was observed between the effects of these dosages. These
      results suggest that DDC possesses punishing properties and that the previously
      reported amnesic properties of DDC are not apparent in all passive avoidance
      tasks.

PMID- 19604857
TI  - Age-related acquisition deficits and activity in rats.
AB  - Spontaneous motor activity and physically undemanding conditioned suppression of
      drinking behavior were assessed in rats of 3, 12, 18 or 30 months (M) age.
      Initial spontaneous motor activity of 12 M rats was as low as that of 30 M rats
      and both were significantly lower than that of 3 M rats. The performance of 3, 12
      and 18 M rats were similar to each other, whereas 30 M rats started to perform
      poorer after one week of training. It is concluded that the acquisition deficits
      observed here in aged rats occur only after 18 months age and appear to be
      independent of the subjects' reactivity to punishment and their activity prior to
      training.

PMID- 19604858
TI  - Mood elevation and pituitary stimulation after i.v. l-5-HTP in normal subjects:
      Evidence for a common serotoninergic mechanism.
AB  - A new soluble ester of l-5-hydroxytryptophan (l-5-HTP (Ro 03-5940) was shown to
      have clear central effects in man following i.v. application after peripheral
      decarboxylase inhibition (Ro 04-4602). A reproducible time course of mood
      elevation in non-depressed subjects was observed up to four hours after l-5-HTP
      infusion in 34 35 experiments, together with stimulation of growth hormone and
      prolactin release. Noteworthy were both the high levels of growth hormone, and
      that the time of peak growth hormone release correlated with peak mood elevation.

PMID- 19604859
TI  - Simultaneous demonstration of horseradish peroxidase and acetylcholinesterase.
AB  - Simultaneous demonstration of acetylcholinesterase (AChE) and horseradish
      peroxidase (HRP) has been achieved by staining frozen sections with a modified
      Koelle-Friedenwald thiocholine method for AChE followed directly by the Graham
      Karnovsky procedure for HRP. By using sodium sulfite instead of sodium sulfide in
      the AChE procedure, the final reaction product appears as black AChE granules
      that contrast sharply with the yellowish-brown HRP granules.

PMID- 19604860
TI  - Barrels in somatosensory cortex of normal and reeler mutant mice.
AB  - The pattern of projection of the ventrobasal thalamic complex (VB) upon the
      neocortical barrel field of normal and reeler mutant mice was determined by
      orthograde degeneration experiments and by Timm's histochemical method. In both
      reeler and normal mice the thalamic terminals are concentrated at the midcortical
      zone dominated by granule cells and the adjacent zone dominated by medium-sized
      pyramidal cells. The medium-sized pyramids are principally supragranular in
      normal cortex but infragranular in the reeler. Throughout the barrel fields of
      reeler and normal mice thalamic terminals are organized as a mosaic of radially
      oriented columns coextensive in the tangential plane with barrels whose cross
      sectional areas and shapes are similar in both genotypes. The radial extent of
      the columns in reeler is 2-3 times that in normal cortex. These observations
      suggest that the tangential organization of the thalamocortical projection is
      normal in reeler and that thalamic terminals are distributed among the same
      neuronal classes in normal and reeler mice despite cell malposition in the
      mutant.

PMID- 19604861
TI  - Competition between motor nerves in the establishment of neuromuscular junctions
      in striated muscles of Xenopus laevis.
AB  - After sectioning one of the two nerves of the pauci-innervated pectoralis muscle
      of Xenopus laevis, a sprouting of the intact nerve is observed in the denervated
      zone. On subsequent reinnvervation by the original nerve, dually innervated end
      plates are found in which the quantal content of the responses to foreign nerve
      stimulation does not change significantly while that from the original nerve
      increases during the course of reinnervation. On the other hand, functional
      innervation from both the original and foreign nerves may persist in the same
      muscle fibre at separated end-plates. It is concluded that original axons depress
      foreign synapses by a local action.

PMID- 19604862
TI  - Early effects of efferent stimulation on the kitten cochlea.
AB  - Kittens from birth to one month were investigated by recording intracochlear
      potentials during electric stimulation of the crossed olivocochlear bundle
      (COCB). From the beginning, COCB stimulation induced strong inhibitory effects on
      cochlear responses to click. As has been demonstrated in the adult, these effects
      were an increase in cochlear microphonic and summating potentials, and a decrease
      in amplitude of the first negative component of the whole nerve action potential.
      Other variations were seen in the newborn animals, such as an increase of the
      amplitude of the second negative component and occurrence of a late negative
      component. The important role of the olivocochlear system during the first
      postnatal week was also demonstrated by comparing the dissipation time of the
      different effects at various stages of postnatal development. The strength of
      efferent inhibition during auditory system maturation is discussed.

PMID- 19604863
TI  - Ultrastructural changes in the nerve terminals of the vascular organ of the
      lamina terminalis in the rat during the estrous cycle.
AB  - Quantitative evaluation of the size of the vesicles in the nerve terminals of the
      vascular organ of the lamina terminalis (OVLT) during the sexual cycle of the
      female rat was made. The results indicate that electron-lucent microvesicles and
      larger vesicles usually with an electron-dense core are found in the examined
      nerve endings at all stages of the cycle, but there is a fluctuation in the ratio
      of these two kinds of vesicles. At proestrus the larger vesicles predominate,
      while at estrus and diestrus the microvesicles prevail. The data are consistent
      with the view that the OVLT may be involved in the control of cyclic
      gonadotrophic function of the anterior pituitary.

PMID- 19604864
TI  - Peripheral factors contributing to the volitional control of firing rates of the
      human motor units.
AB  - Human subjects can volitionally control discharge frequencies of isolated motor
      units at several frequencies. If the tonic firing rates such as 10 Hz are mainly
      dependent on the gamma-loop and if Xylocaine blocks gamma-fibers before blocking
      alpha-fibers, application of Xylocaine would preferentially disturb the tonic
      rates. After application of Xylocaine to the nerve innervating the motor units
      the tonic discharges at 10 Hz became irregular, while the phasic discharges at 1
      Hz could still be performed volitionally. These results suggest that volitional
      control of tonic discharges of the motor units are dependent upon gamma activity,
      while the phasic discharges may be controlled by the impulses along the pyramidal
      tracts.

PMID- 19604865
TI  - 3,4-Dihydroxyphenylacetic acid and homovanillic acid in serum and cerebrospinal
      fluid of psychotic patients estimated by a gas chromatographic method.
AB  - 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) are extracted
      from 0.5 ml serum or cerebrospinal fluid (CSF) with ethyl acetate, reacted with
      pentafluoropropionic anhydride and hexafluoroisopropanol and separated on a 3% SE
      30 gas chromatographic column. In the serum of 13 psychotic patients with
      paranoid-hallucinatory syndrome, mean values of 132 +/- 63 ng/ml DOPAC and 79 +/-
      46 ng/ml HVA were found. The mean concentrations in CSF were 92 +/- 48 and 66 +/-
      28 ng/ml respectively. The results indicate a high intraneuronal metabolism of
      dopamine; the ratio of DOPAC to HVA could give information about the extra- and
      intraneuronal uptake rates of this transmitter.

PMID- 19604866
TI  - Quantitative studies of the brain specific antigens GFA, 14-3-2, synaptin C1, D1,
      D2, D3 and D5 in jimpy mouse.
AB  - Seven antigens specific to the nervous tissue were measured in both Jimpy and
      control mice. The D5 and the GFA protein, both components of the glia, are
      strongly increased in the mutant while the neuronal components 14-3-2, synaptin
      C1, D1, D2 and D3 are unchanged.

PMID- 19604867
TI  - The effect of dl-, l- and d-Propranolol on central monoamine neurones I. Studies
      on dopamine mechanisms.
AB  - dl, l- and d-Propranolol (20 mg/kg) did not change dopamine (DA) levels in
      various regions of the forebrain, but increased DA turnover in subcortical limbic
      regions such as nucleus accumbens, leaving DA turnover in nucleus caudatus and
      median eminence unaffected. Studies on neostriatal DA receptor activity using
      rotational behaviour showed that dl-propranolol (20 mg/kg) increased the action
      of d-amphetamine in this model. The alpha-adrenergic blocking agent piperoxane (5
      mg/kg) preferentially increased DA turnover in nucleus caudatus. It is suggested
      that the antipsychotic action of dl-propranolol is related to an influence on
      limbic DA and not on neostriatal DA mechanisms.

PMID- 19604868
TI  - The effect of dl-, l- and d-propranolol on central monoamine neurones II. Studies
      on noradrenaline mechanisms.
AB  - l-Propranolo (20 mg/kg) reduced noradrenaline (NA) turnover in the cortex
      cerebri, rest of the brain, and periventricular posterior hypothalamus, whereas d
      propranolol (20 mg/kg) increased NA turnover in the two former regions. The
      effects of l-propranolol on NA turnover could not be related to effects on NA
      uptake and release or to effects on NA receptor sites. l-Propranolol may reduce
      NA turnover by acting as an adrenaline agonist on adrenaline receptors located on
      the dendrites and cell bodies of the NA neurones. The antihypertensive action of
      l- and dl-propranolol may also involve an activation of adrenaline receptors
      inter alia those on the NA cells.

PMID- 19604869
TI  - The effects of morphine and naloxone on caudate neuron activities in rats.
AB  - Intracarotid injection of morphine was found to suppress spontaneous neuron
      activities in rat caudate nucleus. This effect was readily reversed by subsequent
      injection of naloxone. The possible mechanism of such morphine-induced inhibition
      is discussed in relation to dopaminergic neurotransmission.

PMID- 19604870
TI  - Spontaneous alternation disturbance after lesions of the ventral mesencephalic
      tegmentum in the rat.
AB  - Radiofrequency lesions of the ventral mesencephalic tegmentum (VMT), a region
      located above the nucleus interpeduncularis, provoked a disappearance of the
      spontaneous alternation behavior. The lesioned rats scores (44%) are not
      different from the chance level, while the alternation rate amounts to 77% in the
      control group. This disturbance cannot be explained by differences in the
      locomotor activity and choice latencies, nor by perseveration tendencies. The
      effects of VMT lesions appear to be of the same nature as those induced by limbic
      forebrain lesions. Anatomical connections between the VMT and the limbic system
      can explain these similarities.

PMID- 19604871
TI  - Non-lateralization of a temporal discrimination task acquired under unilateral
      cortical spreading depression.
AB  - Forty-nine rats were trained for three days to obtain water from a drinking tube
      for every 15th lick. On the next day 44 of them learned under unilateral cortical
      spreading depression to lick for differential reinforcement of low rates of
      responding (minimum interlick interval 6 sec - DRL 6). On day 5 the DRL 6 task
      was retrained with either the contralateral (n = 32) or ipsilateral (n = 12)
      cortical hemisphere depressed. Five rats served as unoperated controls. In all
      three groups DRL performance was significantly improved on day 5. The failure to
      achieve DRL lateralization by functional hemidecortication suggests that DRL
      responding has a strong non-neocortical component.

PMID- 19604872
TI  - Isolation of axolemma-enriched fractions from bovine central nervous system.
AB  - Axolemmal fractions are isolated by discontinuous gradient centrifugation of
      purified myelinated axons which have been osmotically shocked to yield axons,
      myelin and axolemma. The axolemmal fractions are enriched in surface membrane
      marker enzymes such as Na(+),K(+)-activated ATPase, 5'-nucleotidase and
      acetylcholinesterase. Mixing experiments with labeled microsomes and mitochondria
      show that these contaminants are effectively screened out by the preparation
      procedure. The fractions contain significant amounts of 2',3'-cyclic nucleotide
      3'-phosphohydrolase and are enriched in higher molecular weight proteins. These
      membrane preparations may be useful in analytical studies of mammalian axolemmal
      composition.

PMID- 19604873
TI  - Absence of binding of alpha-bungarotoxin and cobra neurotoxin to central
      acetylcholine receptors - an autoradiographic study.
AB  - Radiolabelled alpha-bungarotoxin and cobra neurotoxin, ejected from micropipettes
      in the vicinity of Renshaw cells, failed to label these neurones.

PMID- 19604874
TI  - Quantitative relation between discharge frequencies of a Renshaw cell and an
      intracellularly depolarized motoneuron.
AB  - We present the input-output frequency characteristics of a Renshaw cell which
      could be driven at various frequencies by the discharges of a motoneuron
      depolarized by intracellular current injection. Renshaw cell frequency was
      proportional to motoneuron discharge rate up to about 20 Hz.

PMID- 19604875
TI  - Intracellular recordings from granule cells in the rabbit bulbus olfactorius.
AB  - The bulbus olfactorius of the rabbit provides an easily accessible brain
      structure with well-ordered layers of granule cells. Slices of granule cell
      layers have been utilized for intracellular recordings using microelectrodes with
      bevelled tips of 0.11-0.12 microm diameter. Among the recorded changes in
      membrane potential most frequent are groups of 2-13 wavelets increasing
      continuously in amplitude until finally an impulse is discharged on top of a
      wave. Further, regular sinusoidal rhythms have been observed. As the slow-wave
      activity disappears after treatment with inhibitors of intermediary metabolism,
      such as iodoacetate or malonate, the rhythmic potential changes in granule cells
      appear to be of metabolic origin.

PMID- 19604876
TI  - Dopamine-beta-hydroxylase activity in normal and sympathectomized carotid bodies.
AB  - Normal carotid bodies excised from cats showed DBH values of 5.04 + or - 0.53
      nmol [(3)H]octopamine formed/h/100 mg tissue (x + or - S.E. ). Values from
      sympathectomized carotid bodies were not significantly different. While the
      ganglio-glomerular nerves, providing the sympathetic innervation of the carotid
      bifurcation, had a high DBH level, this was low in the carotid sinus nerve,
      providing its sensory innervation. Glomeral DBH may be contained in a special
      type of noradrenergic glomus cells, distinct from the most common dopaminergic
      glomus cells.

PMID- 19604877
TI  - Antagonism of gamma-hydroxybutyrate-induced hypersynchronization in the ECoG of
      the rat by anti-petit mal drugs.
AB  - Administration of gamma-hydroxybutyrate (GHB) (200 mg/kg i.p.) in rats evoked a
      hypersynchronous electrocorticogram pattern which was antagonized by specific
      anti-petit mal agents, while other antiepileptic drugs exerted no influence, or
      even potentiated the effect of GHB. The specific sensitivity of the GHB-induced
      hypersynchrony to anti-petit mal agents suggests a possible use of this effect as
      a model for testing potential anti-petit mal agents.

PMID- 19604878
TI  - Melatonin-induced changes in the sensory activation of acute epileptic foci.
AB  - Intraperitoneal, intravenous and intracisternal injection of various amounts (50
      1000 microg/kg) of melatonin in cats did not significantly change the focal
      epileptiform activity produced in various cortical areas and limbic structures by
      topical application of various convulsant agents. However, when the focus was
      located in primary sensory areas the sensory evoked activation of the
      epileptiform activity was reduced or suppressed. The present report and other
      literature data support the hypothesis that melatonin may change the response of
      epileptic neurons to sensory stimuli.

PMID- 19604879
TI  - Increased CSF levels of endorphines in chronic psychosis.
AB  - The levels of two endorphines, endogenously occurring morphinomimetic peptides,
      were measured in serial samples of CSF from seven psychiatric patients. Four
      cases with chronic schizophrenia were studied before and after treatment with the
      antipsychotic agent clozapine (Leponex). Supernormal fraction II levels were
      found on at least one sampling occasion in each patient. Two patients, who
      responded well to clozapine treatment, showed a clear-cut drop in fraction II
      levels, whereas two patients showed increased levels which paralleled a
      deterioration of the schizophrenic symptoms. Three manic-depressive cases showed
      abnormally high levels of endorphine fraction I in the manic phase which declined
      during normal or depressed phases. Levels of fraction II varied in a less
      consistent manner and appeared to be at maximum during the apparently normal
      phases. Although preliminary, the data indicate that endorphines may reach
      supernormal levels in patients with chronic psychoses.

PMID- 19604880
TI  - Deficiency of a naturally occurring protein inhibitor in brain of clinically
      'brain damaged' newborn human infants - a possible cause of mental retardation?
AB  - The presence of an inhibitor of guanine deaminase in the 'heavy' mito-chondrial
      fractions of rat brain homogenates has been reported. The results of the present
      study, using brain homogenates from normal infants who died between ages 1-6
      months, low birth weight infants who were brain damaged and died between ages 2
      days-4 months and premature (7-8 months pregnancy) infants, who were considered
      clinical cases with acute brain damage and died 1-3 days after birth, indicate
      that while normal human brain contains the inhibitory material, it is
      conspicuously absent from the particulate fractions of brain damaged low birth
      weight and premature infants. Since brain damage at birth in an infant could
      result in mental retardation of some kind on development, a possible relationship
      between deficiency or absence of the inhibitory material of guanine deaminase in
      human brain and mental retardation is suggested.

PMID- 19604881
TI  - Simultaneous visualization of chromatolytic neurons and neurons retrogradely
      labeled with horseradish peroxidase.
AB  - A method is described for visualization of neurons retrogradely labeled with
      horseradish peroxidase (HRP) in celloidin-embedded brain slabs. The preservation
      of cellular detail obtained with this technique facilitates (1) accurate
      delimination of nuclei or laminae in which HRP-positive neurons are found and (2)
      simultaneous identification of cells of origin of two central fiber systems, by
      combining the retrograde transport of HRP and the retrotrade degeneration
      technique. The latter approach has been used in adult cats and in kittens to
      identify cortical neurons which project to the dorsal column nuclei and to the
      spinal cord.

PMID- 19604882
TI  - Spinocervical tract cells in cat and dog, labeled by the retrograde transport of
      horseradish peroxidase.
AB  - The location of cells of origin of the spinocervical tract has been determined in
      cat and dog by injecting horseradish peroxidase into the lateral cervical nucleus
      (LCN). Retrogradely labeled cells were found predominantly in the ipsilateral
      nucleus proprius of the dorsal horn along the entire spinal cord. Cells of
      Clarke's column and contralateral ventral horn cells were not labeled, in
      agreement with previous electrophysiological indications that the spinocerebellar
      tracts do not maintain collateral terminations in the LCN.

PMID- 19604883
TI  - Cells of origin of hypothalamo-spinal projections in the rat.
AB  - The retrograde transport of horseradish peroxidase (HRP) was used to determine
      the distribution of hypothalamic neurons which send axonal projections to the
      spinal cord. Labeled cells were observed in the paraventricular nucleus (PV) and
      in the lateral hypothalamic area following HRP injections into the lower thoracic
      and upper lumbar spinal cords of rats. In PV, the HRP-labeled cells were located
      in the parvocellular portion of the nucleus. Hypothalamo-spinal projections are
      predominantly uncrossed.

PMID- 19604884
TI  - Effects of apomorphine and haloperidol on somatopetal transport of horseradish
      peroxidase in the nigro-striatal pathway.
AB  - Labeling of cell bodies in pars compacta of substantia nigra (SNc) following
      injections of horseradish peroxidase (HRP) in the neostriatum was not affected by
      repeated systemic injections of apomorphine or haloperidol during the survival
      time. These drugs decelerate and accelerate, respectively, the firing of SNc
      neurons. Provided the used standard method was sensitive enough, it could be
      concluded that at least in these neurons the somatopetal transport and
      accumulation of the tracer do not depend on the rate of electrical activity.
      Consequently, the intensity of labeling with HRP is not a sensitive index of
      neuronal activity.

PMID- 19604885
TI  - Retrograde labeling of central nervous pathways with tritiated or Evans blue
      labeled bovine serum albumin.
AB  - In an attempt to develop a technique for the retrograde tracing of neuronal
      pathways which does not depend on enzyme activity of horseradish peroxidase
      (HRP), we have examined the retrograde transport of bovine serum albumin (BSA) by
      neurons of the central nervous system. Following injections of either tritiated
      or Evans blue-labeled BSA into the hippocampal formation of the rat, labeled
      neurons were found in the ipsilateral entorhinal area in a pattern which was
      highly reminiscent of that obtained with HRP. The retrograde transport of BSA
      provides a method for the retrograde tracing of central nervous pathways which is
      completely independent of the HRP method, making it possible to use both
      substances for studies of collateral innervation, and can be used with any
      fixative, or no fixative at all.

PMID- 19604886
TI  - An electron microscopic study on the development of synapses in the rat carotid
      body.
AB  - The number of types 1 and 2 synapses on chief cells per unit area in the rat
      carotid body were compared throughout pre- and postnatal periods. Chief cells are
      postsynaptic in type 1 synapses and presynaptic in type 2 synapses. Type 2
      synapses increased in number rapidly as development proceeded, while type 1
      synapses remained few. By the 50th postnatal day the numerical density of
      synapses of both types reached a plateau, where type 2 synapses were
      approximately 22 times more numerous than type 1 synapses. The present findings
      suggest that nerve fibers innervating chief cells of the carotid body are
      basically sensory.

PMID- 19604887
TI  - Histochemical evidence for the degeneration of peripheral noradrenergic axons
      following intravenous injection of antibodies to dopamine-beta-hydroxylase.
AB  - Noradrenergic axons in the intestine, mesentery, atrium, vas deferens and iris of
      the guinea-pig were examined histochemically for the presence of noradrenaline
      and dopamine-beta-hydroxylase (DBH) at various times after the intravenous
      injection of antibodies to DBH. Swollen, degenerating axons were found in the
      intestine and atria in the first 1-5 days and, by the fifth day, most of the
      axons containing noradrenaline and DBH had disappeared. At the same time, there
      were accumulations of noradrenaline and DBH in non-terminal noradrenergic axons
      supplying these organs. No morphological evidence of degeneration of axons in the
      iris and vas deferens was found under the same experimental conditions.

PMID- 19604888
TI  - Changes in tyrosine hydroxylase and dopamine-beta-hydroxylase activities during
      degeneration of noradrenergic axons produced by antibodies to dopamine-beta
      hydroxylase.
AB  - Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities were
      measured in various tissues of guinea-pigs 1-21 days after intravenous injection
      of antiserum against DBH. At 5 days a significant reduction in tissue levels of
      DBH was observed in all tissues measured although the extent of depletion was
      variable. TH in the heart and vas deferens showed a parallel reduction to DBH. At
      21 days tissue DBH and TH had partially recovered. Plasma DBH was reduced at 21
      days whereas adrenal TH was markedly elevated. These findings support the
      morphological evidence that antibodies against DBH produce a specific
      degeneration of peripheral noradrenergic nerves.

PMID- 19604889
TI  - Time constants of the slow velocity responses of deefferented primary muscle
      spindle endings.
AB  - Responses to ramp muscle stretches of constant amplitude (10 mm) and varying
      velocity (0.4-70 mm/sec) were recorded from deefferented primary spindle endings
      in the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles of the
      cat. A linear model was applied to the relationship between peak frequency at
      ramp offset and velocity and estimates of the time constants of the slow velocity
      responses were made by fitting theoretical curves to the experimental data. A
      satisfactory fit was obtained with two time constants, one always taken as 90
      sec, the other ranging from 1.0 to 2.3 sec for TA and from 2.5 to 4.0 sec for
      EDL.

PMID- 19604891
TI  - Evidence that supersensitivity after recovery from 6-hydroxydopamine is an
      artifact of isolation housing.
AB  - Rats were administered intraventricular injections of 6-hydroxydopamine (6-OHDA)
      and allowed to recover in either isolation cages or in an enriched, non-crowded
      rat colony environment. When tested 45 days after 6-OHDA, the animals allowed to
      recover in isolation cages were hyperirritable, reared more in open field than
      did isolated controls, and showed exaggerated responsivity to d-amphetamine. None
      of these effects, which have been ascribed to the development of
      supersensitivity, were present in the rats allowed to recover in the colony
      environment. This implies that the process of recovery from 6-OHDA is different
      in isolated and enriched social environments.

PMID- 19604890
TI  - Cooling of the nucleus raphe dorsalis induces sleep in the cat.
AB  - Localized moderate cooling (+10 degrees C) of the anterior and ventral part of
      the raphe dorsalis induced cortical synchronization and ponto-geniculo-occipital
      (PGO) waves followed sometimes by paradoxical sleep. Cooling the region of the
      raphe magnus produced cortical arousal. After depletion of brain 5
      hydroxytryptamine (5-HT) by para-chlorophenylalanine, cooling the raphe dorsalis
      resulted in muscle atonia and bursts of high frequency PGO waves but not in
      cortical synchronization. Following restoration of brain 5-HT by intravenous
      administration of 5-hydroxytryptophan, cooling again produced cortical
      synchronization and PGO waves as in the control experiments, but with a
      diminishing efficacy during repetitive cooling episodes.

PMID- 19604892
TI  - Golgi-like staining of neocortical neurons using retrogradely transported
      horseradish peroxidase.
AB  - Neocortical pyramidal neurons stained solidly with horseradish peroxidase (HRP)
      two days after striatal, thalamic or cortical HRP injections are described in the
      rabbit, rat and marmoset monkey. The dendritic detail seen in these solid HRP
      labeled neurons approaches that produced by the Golgi method.

PMID- 19604893
TI  - Rhombo-mesencephalic connections in the fast conducting electrosensory system of
      the mormyrid fish, Gnathonemus petersii. An HRP study.
AB  - Using retrograde horseradish peroxidase (HRP) axonal transport direct rhombo
      mesencephalic connections were revealed in Gnathonemus petersii. By HRP injection
      in the neuropil of the extrolateral mesencephalic ganglion the neurons of the
      lateral line lobe nucleus were labeled. The pathway is mainly composed of crossed
      fibers.

PMID- 19604894
TI  - Cells of origin of cortical projections to dorsal column nuclei, spinal cord and
      bulbar medial reticular formation in the rhesus monkey.
AB  - Cells of origin of cortical fibers to the dorsal column nuclei, spinal cord and
      bulbar medial reticular formation were identified in 8 rhesus monkeys by means of
      the horseradish peroxidase (HRP) retrograde transport technique. After dorsal
      column nuclei injections small pyramidal neurons were labeled in the
      contralateral hemisphere in layer V of areas 3, 1, 2 and 5 and in layer V of the
      posterior part of area 4. In contrast, after spinal cord injections many area 4
      giant Betz cells in the contralateral hemisphere were labeled as well as many
      other layer V pyramidal neurons in areas 4 and posterior 6 and in areas 3, 1, 2
      and 5. Injections in the bulbar medial reticular formation labeled mainly medium
      sized layer V pyramidal neurons in area 6 and the anterior part of area 4 of both
      hemipsheres.

PMID- 19604895
TI  - Rapid degeneration of visual fibers following retinal lesions in the dipteran
      compound eye.
AB  - Cutting the peripheral retina of the compound eye of the fly resulted in an
      extremely rapid degeneration, within minutes, of the receptor cells, first in the
      pseudocartridges and the lamina and then, in the case of the central receptor
      cells R7 and R8, in the medulla. The degenerative changes evident in the lamina
      and medulla occurred before any changes were seen in the proximal retina (the
      part of the cells nearest the cut surface).

PMID- 19604896
TI  - Responses of single units in the pontine nuclei of the cat to acoustic
      stimulation.
AB  - Auditory responses of single units in the pontine nuclei of the anaesthetized cat
      were studied electrophysiologically. Many units in the pontine nuclei, and in
      particular the dorsolateral pontine nucleus were strongly driven by the onset of
      auditory tonal stimuli in a broadly tuned manner. Most units were excited by
      stimulation of each ear and demonstrated binaural facilitation. Also, many
      pontine units responded to visual stimuli and some were bimodally active. These
      response properties are similar to those of units recorded in the cerebellar
      vermis which probably receives auditory and visual input from the pontine nuclei.

PMID- 19604897
TI  - Responses evoked in mouse and rat SI cortex by vibrissa stimulation.
AB  - Surface evoked and single unit responses to vibrissa stimulation were
      investigated in the PosteroMedial Barrel SubField (PMBSF) area of rat and mouse
      SI cortex. The data strongly suggest a correspondence between the focal point of
      the surface projection region and the underlying barrel hollow. Units activated
      by the whisker movement were recorded in all cortical layers. They responded
      mainly in a phasic manner. Units sensitive to direction of stimulation as well as
      units receiving functional convergence from more than one vibrissa are described.

PMID- 19604898
TI  - Response of medullary neurons to step changes in carotid sinus pressure.
AB  - Moderate amplitude step changes in carotid sinus pressure were found, in an open
      loop baroreflex preparation, to produce equivalent step changes in the firing
      rate of a majority of the medullary neurons tested. The average firing rate
      remained constant so long as the pressure was held constant (up to 24 sec). No
      rate sensitivity was observed in 32 out of 33 neurons; however, a single neuron
      showed mean firing rate changes only during pressure transitions. The variety in
      the activity patterns of cells which, on the average exhibited stereotyped
      responses to a simple repetitive stimulus, suggests that afferent information may
      undergo considerable integration and restructuring within the sensory nucleus,
      rather than being 'relayed' intact to other regions.

PMID- 19604899
TI  - Mammalian endocrine neurones: Control of phasic activity by antidromic action
      potentials.
AB  - Hypothalamic supraoptic neurones were identified by antidromic invasion following
      stimulation of the pituitary stalk in urethane anaesthetized rats. These
      endocrine neurones either discharged continuously at low average rates (random)
      or were intermittently active (phasic). Phasic cells are thought to be
      vasopressinergic. With phasic neurones, antidromic activation with short trains
      of stimuli during the quiescent period triggered the 'on-phase' of spike
      discharge, and the probability of this response increased as the 'off-phase'
      progressed. Stimulation was ineffective in triggering high frequency firing when
      applied below the threshold for antidromic invasion, and caused no parallel
      response of random neurones. Arrest of firing during the 'on-phase' was achieved
      by stimulation with higher currents and longer pulse trains. These studies
      demonstrate that the switching process determining the firing pattern of phasic
      neurones depends on the cells' ongoing activity. Further, they reveal progressive
      changes in the cells' capacity to alter their electrophysiological state, a
      capacity that is not expressed in terms of the temporal pattern of spike
      discharges.

PMID- 19604900
TI  - Characterization and topography of LH-RH neurons in the human brain.
AB  - The localization of luteinizing hormone-releasing hormone (LH-RH) has been
      studied in the human brain with the indirect immunofluorescence technique. LH-RH
      positive perikarya are scattered from the septo-preoptic region up to the
      retromammillary area and give rise to two main tracts ending in the infundibulum
      and the lamina terminalis.

PMID- 19604901
TI  - Immunocytochemical evidence for the association of neurophysin-I with vasopressin
      and neurophysin-II with oxytocin in the pig hypothalamus.
AB  - Antisera raised against oxytocin, [8-arginine]-vasopressin, porcine neurophysin-I
      and porcine neurophysin-II were used to localize the neurohypophysial hormones
      and neurophysins in the paraventricular nucleus (PVN) of the pig using
      immunoenzyme cytochemical techniques. In sagittal section, the dorsolateral part
      of the PVN appeared as a densely populated group of cells which stained heavily
      for neurophysin-I and vasopressin with only a few neurons staining for
      neurophysin-II and oxytocin.

PMID- 19604902
TI  - Evidence for local angiotensin formation in brain of nephrectomized rats.
AB  - Twenty-four nephrectomized rats were infused intracranially with angiotensin II
      (AII), synthetic tetradecapeptide substrate and purified rat and dog plasma
      substrates. Significant drinking responses were observed with all four
      substances. Drinking to the renin substrate infusions was inhibited by
      intracranial infusions of either angiotensin I-converting enzyme inhibitor (SQ
      20881) or a specific AII antagonist, saralasin, indicating that conversion of the
      substrates to AII was a necessary step in order to produce the drinking
      responses. These results indicate that brain iso-renin can operate under
      physiological conditions to produce angiotensin from both synthetic and naturally
      occurring substrates.

PMID- 19604903
TI  - Inhibitory action of midbrain raphe stimulation on stress-induced elevation of
      plasma corticosterone level in rats.
AB  - Electric stimulation of rat midbrain raphe nuclei by means of chronically
      implanted bipolar electrodes was able to reduce the stress-induced increase in
      plasma corticosterone level by about 40-50%. A serotonin receptor blocker,
      methysergide, prevented the stimulation-induced inhibition of the stress
      response. The results support the possible existence of serotoninergic inhibition
      of hypothalamo-pituitary-adrenocortical activation in rats.

PMID- 19604904
TI  - Calcium content of mice brain lipids during myelination.
AB  - Calcium levels have been determined in brain of C57Bl mice and in the Quaking
      dysmyelinating mutant during the myelination period. In control mice, calcium
      content per gram brain is maximum at 20 days, at the acme of myelination, and
      decreases thereafter to reach a plateau at 30 days. This variation does not occur
      in the mutant where the level is 50% lower than maximum in controls and stable at
      15 days after birth. In control mice, the variation may be related to the level
      or to the qualitative variation of some glycolipids and proteolipids as it
      disappears in lipid extract after Folch wash.

PMID- 19604905
TI  - Calcium decrease associated with aminopyridine-induced potassium increase in cat
      cerebellum.
AB  - Ca(2+)- and K(+)-selective micropipettes were paired to measure extracellular ion
      changes in cat cerebellum superfused with aminopyridine-Ringer solution. A single
      shock to the cerebellar surface evoked a large transient Ca(2+) decrease and K(+)
      increase. Spatially, the ion changes were unequal, with the Ca(2+) decrease
      localized in the synaptically active region. The ion changes were reversibly
      abolished when citrate was added to the superfusate. The ion transients are
      comparable to those in spreading depression and indicate that aminopyridine may
      enhance Ca(2+) membrane currents.

PMID- 19604906
TI  - Presetting of excitability of the spinal Ia inhibitory pathway in relation to the
      direction of an intended movement.
AB  - The spinal Ia inhibitory pathway which reciprocally inhibits hindlimb extensor
      motoneurons was found to be potentiated when human subjects were prepared, but
      not initiated, to perform a quick dorsiflexion at the ankle in response to a
      somesthetic stimulus.

PMID- 19604907
TI  - Development of locomotor activities in young chronic spinal rabbits.
AB  - It was previously demonstrated that adult chronic spinal rabbits do not recover
      any spontaneous locomotor activity of the hindlimbs. Pharmacological stimuli may,
      nevertheless, evoke locomotor activities in the acute spinal animal; however, the
      pattern is alternate between both hindlimbs instead of being symmetrical (normal
      pattern in the intact animal). Present data indicate that young rabbits whose
      spinal cord was transected at birth can recover and spontaneously develop
      hindlimb locomotor movements over a period of one month after spinal section.
      These rhythmic activities are either synchronous or alternate between the two
      sides, or both. It is concluded that not only the alternate pattern but also a
      pure synchronous one can be generated in the lumbosacral cord in the young
      chronic spinal rabbit.

PMID- 19604908
TI  - The nucleus accumbens of rats and dopaminergic mechanisms regulating locomotor
      behaviour.
AB  - Dopamine and (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) were injected into
      the nucleus accumbens of rats locally pretreated with ergometrine. The results
      show that the ergometrine-induced locomotor activity is inhibited by both
      compounds suggesting that ergometrine inhibits certain types of dopamine
      receptors. The data are discussed in terms of distinct types of dopamine
      receptors.

PMID- 19604909
TI  - 5-Hydroxytryptamine depletion and avoidance acquisition in the rat. Antagonism of
      the long-term effects of p-chloroamphetamine with a selective inhibitor of 5
      hydroxytryptamine uptake.
AB  - Twenty four male Sprague-Dawley albino rats in three equal (n = 8) groups were
      injected on two consecutive days with either p-chloroamphetamine hydrochloride
      (PCA) (10 mg/kg), H 102/09, an inhibitor of 5-hydroxytryptamine (5-HT) uptake (20
      mg/kg) half an hour before PCA, or saline (1 ml/kg). Seven days later the
      acquisition of a two-way active avoidance response was studied in 8 daily
      sessions of 20 trials. PCA injections reduced 5-HT concentration of the whole
      brain 64% at the end of testing (15th day) whereas pretreatment with H 102/09
      completely blocked this effect. PCA-treated rats were severely retarded in
      learning the avoidance response but there was no change in the acquisition of the
      escape. In contrast, rats pretreated with H 102/09 acquired the avoidance
      response as rapidly as the saline control group. These results suggest that the
      impaired learning of the two-way avoidance response may be related to the long
      term effects of PCA on the 5-HT neurons in the rat brain. It is concluded that 5
      HT neurons may play a role in acquisition of behaviors motivated by aversive
      events.

PMID- 19604910
TI  - Changes in paradoxical sleep accompanying instrumental learning in the cat.
AB  - Five animals were used as their own controls for a replication on cats of earlier
      findings of facilitated paradoxical sleep (PS) after learning. The experiment was
      based on an instrumental conditioning with positive reinforcement and three-hour
      recordings of the subsequent sleep. Facilitation was observed as (a) an increase
      in the amount of PS during the first 45 min of sleep, (b) an increase in PS
      episode duration, (c) a decrease in PS latencies and (d) a decrease in slow wave
      duration versus PS episode duration in the early sleep cycles. The lengthening of
      PS phases was the only change closely correlated with the state of acquisition.

PMID- 19604911
TI  - Corticostriatal cells identified by the peroxidase method.
AB  - Corticostriatal cells in rat neocortex were identified by the peroxidase
      retrograde axonal transport method as neurons restricted to layer V, found in the
      whole radial extent of layer V, and comprising cells of all sizes and shapes.
      Usually the largest pyramidal cells were not labeled.

PMID- 19604912
TI  - A bilateral cortical projection to the superior colliculus in the cat.
AB  - Projections from the cerebral cortex to the superior colliculus (SC) of the cat
      have been determined by injecting horseradish peroxidase (HRP) unilaterally into
      SC. In addition to labelled cells found in the visual areas ipsilateral to the
      injection site, HRP-positive neurones were observed in the lateral bank of the
      suprasylvian sulcus of both hemispheres. This region, the suprasylvian fringe,
      which is part of the auditory cortex, apparently projects bilaterally to the SC.

PMID- 19604914
TI  - The time of origin of Cajal-Retzius cells in the rat temporal cortex. An
      autoradiographic study.
AB  - Rat fetuses received tritiated thymidine on one of each of the following days of
      gestation: 9, 10, 11, 12, 13, 14 and 16. Animals were sacrificed on day 1 post
      partum. Perpendicular and tangential sections including temporal cortex were
      studied by electron microscopy and light microscopic autoradiography. Our results
      suggest that the formation of Cajal-Retzius cells (CRs) begins on day 12, reaches
      a peak on day 13, and continues on day 14. Earliest non-CR neurons of the
      temporal cortex (cells of the deepest stratum of layer VI) appear to be generated
      on day 13.

PMID- 19604913
TI  - Synaptogenesis in the cerebral hemisphere (accessory hyperstriatum) of the chick
      embryo.
AB  - Axosomatic and axodendritic synapses, containing almost exclusively spherical
      clear vesicles, were first detected in the embryonic chick hyperstriatal complex
      at about 10 days of incubation. Axodendritic synapses gradually become more
      plentiful during the subsequent week in ovo, while axosomatic synapses remain
      scarce at all stages. An explosive formation of new synapses, all of them packed
      with spherical clear vesicles, occurs shortly before hatching. This event
      coincides with rapid maturation of the dendritic branches, especially with
      respect to spine formation.

PMID- 19604915
TI  - Immunohistochemical localization of luteinizing hormone-releasing hormone (LH-RH)
      and somatostatin in the organum vasculosum of the lamina terminalis of the rat.
AB  - The role of the organum vasculosum of the lamina terminalis (OVLT) is almost
      completely unknown. In order to identify the content of the nervous structures
      present in this organ, we have localized by immunohistochemistry at both light
      and electron microscope levels two hypothalamic regulatory hormones: luteinizing
      hormone-releasing hormone (LH-RH) and somatostatin. It has been found that both
      LH-RH and somatostatin are localized in the nerve endings located at the
      proximity of the capillaries of the organum vasculosum. The two hormones are
      likely contained in different categories of nerve endings. The physiological
      importance of this organ still remains to be elucidated.

PMID- 19604916
TI  - Local degradation of growth hormone-release-inhibiting hormone (somatostatin) in
      the central nervous system.
AB  - Peptidases inactivating growth hormone-release-inhibiting hormone (somatostatin)
      were found to be present in two fractions prepared from the thalamus,
      hypothalamus, cortex and cerebellum of male and female rats. Somatostatin was
      also detected in significant quantities in fractions from the thalamus,
      hypothalamus, and cortex, after peptidase activity had been removed by heat
      denaturation. These results support the suggestion that somatostatin may function
      as a neurotransmitter or modulator of neuronal activity in the central nervous
      system.

PMID- 19604917
TI  - Interaction between rod and cone systems in dichoptic visual masking.
AB  - The brightness of a brief flash of light is reduced by the suitable presentation
      of a second flash in an adjacent region of the visual field. This making effect
      (metacontrast) can be induced dichoptically, that is with the test flash
      presented to one eye and the masking flash to the other. By a suitable choice of
      wavelengths and conditioning field, the test flash may be arranged to effectively
      stimulate only rod receptors and the masking flash only cone receptor. A
      dichoptic masking effect is still obtained.

PMID- 19604918
TI  - Smooth pursuit eye movements elicited by somatosensory stimulation.
AB  - Smooth pursuit eye movements approaching the qualitative and quantitative
      characteristics of those elicited by a moving visual target were obtained in
      complete darkness with a moving tactile stimulus. Pursuit eye movements in
      response to tactile stimulation have longer latencies to onset and to offset of
      pursuit, are more often interrupted by saccades, and provide less accurate
      stimulus localization than those in response to moving visual stimuli. The
      evocation of pursuit eye movements by a somatosensory input suggests that within
      the appropriate velocity domain a spatially changing sensory input from any
      modality may be sufficient to elicit ocular pursuit.

PMID- 19604919
TI  - Specific anosmia to geraniol in mice.
AB  - The ability of Swiss mice to detect geraniol, menthol, benzaldehyde, and
      salicylaldehyde was tested by an active avoidance paradigm. Fourteen animals with
      specific anosmia to geraniol were obtained. Of these, seven were also unable to
      detect phenylethyl alcohol. Both compounds have similar odor quality in humans
      and are believed to stimulate the same receptors. The data on the specifically
      anosmic mice suggest that these structurally dissimilar compounds are detected by
      the same receptors in mice.

PMID- 19604920
TI  - Effects of Gabaculine on the uptake, binding and metabolism of GABA.
AB  - Gabaculine, a conformationally restricted analogue of GABA, is (i) a moderately
      potent inhibitor (IC(50) 69 muM) of the sodium-dependent uptake of GABA in rat
      brain slices, (ii) ineffective at 100 muM as an inhibitor of the sodium
      independent binding of GABA to membranes from rat brain, (iii) a relatively weak
      inhibitor (IC(50) > 1 mM) of glutamate decarboxylase activity in tracts of rat
      brain, and (iv) a very potent inhibitor (IC(50) 3 muM) of the transamination of
      GABA catalyzed by extracts of rat brain mitochondria. Inhibition of
      transamination is time-dependent and follows pseudo-first order kinetics, which
      is consistent with gabaculine acting as a catalytic inhibitor at the active site.

PMID- 19604921
TI  - Effect of chronic manganese intoxication on the sleep-wake cycle in the rat.
AB  - Chronic manganese intoxication elicits in the rat an increase in slow wave sleep
      and a decrease in paradoxical sleep by modification of the length of the phases.
      The similarities between this observation and the sleep disturbances observed in
      man in Parkinson's disease and chronic manganese poisoning are discussed.

PMID- 19604922
TI  - Tetanus toxin: Retrograde axonal transport of systemically administered toxin.
AB  - After intramuscular injection, [(125)I] tetanus toxin is carried to spinal motor
      neurons by retrograde axonal transport. In the present study, we asked whether
      systemically administered toxin can be transported toward the spinal cord via
      this intraaxonal pathway. Mice were given [(125)I] tetanus toxin
      intraperitoneally, one sciatic nerve was ligated and, 24 h later, the animals
      were perfused. Autoradiograms showed labeled toxin accumulated within axons
      distal to the ligature. We interpret these findings as indicating that
      circulating toxin can leak out of intramuscular capillaries, be taken up at nerve
      terminals, and subsequently be carried toward the spinal cord by retrograde
      axonal transport. This pathway may be an important route by which systemically
      administered toxin can reach the CNS.

PMID- 19604923
TI  - Responses of muscle spindles to stretch after a period of fusimotor activity
      compared in freely moving and anaesthetized cats.
AB  - Recordings of responses of muscle spindles in the soleus muscle of freely moving
      unanaesthetized cats show that the onset of receptor discharge during the portion
      of the step cycle in which the muscle is stretched is earlier when compared with
      a similar stretch applied in the anaesthetized animal. In anaesthetized animals
      the response to stretch also commences earlier if the movement is preceded by
      fusimotor activity. It is suggested that the relatively long time-course of
      intrafusal relaxation, as well as an associated increase in compliance of
      intrafusal fibres, can account for the early onset in the response to stretch.

PMID- 19604924
TI  - Effects of pentylenetetrazol on resting membrane potential and on action
      potentials of mammalian dorsal root ganglion cells grown in tissue culture.
AB  - The effects of pentylenetetrazol (PTZ) on resting membrane potential (RMP) and on
      action potentials (AP) of dorsal root ganglion cells of the rat in tissue culture
      were studied. PTZ usually evoked a hyperpolarization which was followed by a
      depolarization. The hyperpolarization diminished with increasing initial MP and
      was absent at about 80 mV. Latency and amplitude of the depolarization decreased
      and increased, respectively, when the PTZ concentration was raised. Paroxysmal
      depolarization shifts did not occur. AP generation was depressed independently
      from RMP fluctuations.

PMID- 19604925
TI  - Maintenance of intracranial self-stimulation in hippocampus and olfactory bulb
      following regional depletion of noradrenaline.
AB  - As a test of the 'noradrenergic' theory of brain-stimulation reward rats were
      trained to respond for stimulation at sites in the hippocampus and olfactory
      bulb. Inasmuch as there is evidence that the noradrenergic innervation of these
      two areas arisesexclusively from the locus coeruleus, the effects of 6
      hydroxydopamine-induced lesions of this protection on hippocampal and olfactory
      bulb self-stimulation were examined. Depletion of hippocampal noradrenaline
      levels to less than 5% and olfactory bulb levels to less than 9% of controls had
      no significant effect on self-stimulation at these loci. Therefore noradrenaline
      does not seem to be an essential substrate of brain-stimulation reward in these
      regions of the brain. The effect of this lesion on the rate-increasing properties
      of d-amphetamine sulphate (1.0 mg/kg) was also examined with hippocampal
      placements. A significant increase in self-stimulation rate was observed both
      before and after the lesion, thus questioning traditional explanations of the
      facilitatory effect of amphetamine on self-stimulation.

PMID- 19604926
TI  - Sleep: Control of the paradoxical episode?
AB  - Cooling of the medial aspects of the midbrain tegmentum produces high voltage EEG
      rhythms and behavioral depression. This same procedure carried out in cats
      pretreated with parachlorophenylalanine between post-drug hours 20 and 60
      produces a state exhibiting the tonic and phasic EEG, EOG, EMG and gross
      behavioral criteria of the paradoxical episode of sleep.

PMID- 19604927
TI  - The role of the stria terminalis as an efferent amygdaloid pathway.
AB  - Extracellular action potentials were recorded from spontaneously active
      septopreoptic neurones responding to amygdala stimulation in the urethane
      anaesthetized rat. Initial responses were either excitation or inhibition. All
      responses contained an inhibitory component and were characterized according to
      postinhibitory excitation. Response characteristics or firing rates were not
      altered by ipsilateral or bilateral lesion of the stria terminalis (ST). It is
      suggested that impulses from the amygdala that influence ovulation, as well as
      several other functions, may travel in the ventral amygdalofugal pathway (VAF).

PMID- 19604928
TI  - Periaqueductal grey lesions reduce morphine analgesia in the rat.
AB  - Many recent experiments have implicated the periaqueductal grey matter (PAG) as a
      major site of action of morphine in producing analgesia. This hypothesis was
      tested by investigating the effect of PAG lesions on morphine analgesia.
      Histologically verified electrolytic lesions were made in the rat mesencephalon
      which destroyed a large part of the PAG. Rats were subsequently tested for
      morphine analgesia using the tail flick method. Analgesin produced by morphine
      administration was markedly reduced in the lesioned rats. Pain thresholds were
      not altered by the lesions.

PMID- 19604929
TI  - Effects of intranigral application of dopamine and substance P on the in vivo
      release of newly synthesized [(3)H]-dopamine in the ipsilateral caudate nucleus
      of the cat.
AB  - The effects of intranigral applications of dopamine (DA) and substance P on the
      release of DA in the ipsilateral caudate nucleus were examined in vivo in the
      'encephale isole' cat preparation. A push-pull cannula was inserted into the
      caudate nucleus to measure the release of [(3)H]DA continuously synthesized from
      l-[3,5-(3)H]tyrosine. DA (10(-7) M) and substance P (10(-8) M) were introduced
      for a period of one hour into the substantia nigra using a second push-pull
      cannula. The superfusion of substantia nigra with DA was associated with a
      decrease in [(3)H]DA release in the caudate nucleus. Substance P induced an
      opposite effect.

PMID- 19604930
TI  - Effect of strychnine on cardiac vagal inhibition.
AB  - Strychnine blocked the vagal-induced cardiac inhibition in both perfused frog
      heart and dog's heart in situ. This effect was antagonized by eserine. The
      present results are consistent with our previous findings that strychnine blocks
      the cholinergic inhibitory mechanisms both in the central nervous system as well
      as in the peripheral autonomic nervous system.

PMID- 19604931
TI  - A glycoprotein resembling a peripheral nicotinic acetylcholine receptor that
      binds [(125)I]-alpha-bungarotoxin in mouse brain.
AB  - A protein that binds alpha-bungarotoxin (alpha-BGT) was found in mouse brain and
      purified by means of Sepharose 6B column chromatography. The binding was
      inhibited by d-tubocurarine but not by atropine. This component was a
      glycoprotein with a molecular weight of 7 x 10(5) determined by gel
      chromatography, an apparent S value of approximately 11 determined by sucrose
      density gradient centrifugation and an isoelectric point of 5.6. The results
      showed that the component resembled a nicotinic acetylcholine receptor (AChR) in
      skeletal muscle and in electric organs.

PMID- 19604932
TI  - The cortical projections of the thalamic intralaminar nuclei restudied by means
      of the HRP retrograde axonal transport.
AB  - Following multiple injections of HRP in different cortical areas in the cat,
      labeled cells were, in some cases, found in the thalamic intralaminar nuclei. The
      following cortical zones were found to constitute the preferential target for the
      projections from the respective intralaminar nuclei: motor and anterior
      suprasylvian areas for the nucleus centralis lateralis, cingulate cortex for the
      nuclei paracentralis and centralis medialis, sensory and motor areas for the
      nucleus centrum medianum. These data are compared with the results previously
      obtained by means of the retrograde degeneration technique.

PMID- 19604933
TI  - The immunohistochemical demonstration of noradrenergic neurons in the rat brain:
      The use of homologous antiserum to dopamine-beta-hydroxylase.
AB  - The immunohistochemical localization of dopamine-beta-hydroxylase (DBH) in
      central noradrenergic neurons of the rat is greatly improved by the use of
      homologous antiserum (i.e. antibody against purified rat DBH). This antiserum,
      which has a several thousand-fold greater affinity for rat DBH than does
      heterologous antibody, is used at a 1:500 dilution with low concentrations of
      detergent. This method applied to paraformaldehyde-perfused tissue consistently
      yields highly sensitive and selective staining with excellent cytologic
      preservation of fine neuronal processes.

PMID- 19604934
TI  - Topographic distribution of visual and somesthesic unitary responses in the Pul
      LP complex of the cat.
AB  - An electrophysiological analysis of field potentials and unitary responses evoked
      by visual, acoustic and somesthesic stimuli in thalamic associative nuclei was
      performed in 'encephale isole' cats. Photic responses were particularly
      pronounced in the pulvinar nucleus (Pul) including its inferior division, while
      in lateralis posterior (LP) and, to a lesser extent, in the posterior nuclear
      group (PO) a prevalence of somesthesic responses was found. Only a few units were
      influenced by the acoustic (clicks) stimulation. Unitary convergence and
      interaction was a characteristic common to all divisions of Pul-LP complex. Areas
      of different functional significance can therefore be traced into the associative
      thalamic posterior nuclei, according to their modal sensitivity. The topographic
      functional organization is in partial agreement with the distribution of afferent
      connections shown by previous anatomical studies.

PMID- 19604935
TI  - Stretch-sensitive mechanoreceptors in the frog sartorius muscle.
AB  - The sartorius muscle of the frog Litoria aurea contains two populations of
      mechanoreceptors. Commonest are the muscle spindles served by afferent fibres
      conducting at 24-42 m/sec. Each muscles also contains two or three high threshold
      receptors identified as extrafusal receptors with afferents conducting at 14-22
      m/sec. Extrafusal receptors unlike spindles did not show a resting discharge even
      in the presence of high levels of resting tension in the muscle. Furthermore
      their responses to both stretch and contraction were weak and variable. It is
      concluded that extrafusal receptors should not be compared with muscle spindles
      or tendon organs but with the high threshold pressure and nociceptors known to
      occur in mammalian muscle.

PMID- 19604936
TI  - Membrane properties of a human neuroblastoma.
AB  - The electrical properties of the SK-N-SH human neuroblastoma cell were studied by
      standard intracellular recording techniques; the average resting membrane
      potential was -21 +/- 11 mV, with a few cells showing mebrane potentials greater
      than - 40 mV. Under standard tissue culture conditions, as used in these
      experiments, less than 1% of these cells show morphological differentiation
      (process formation). In response to current injection, a variety of graded
      responses with a relatively slow rise time were observed. In some cells only
      delayed rectification was observed. In no instance did current injection result
      in a characteristic action potential. An analogous method for determining
      electrical excitability was to measure (22)Na influx in the presence and absence
      of a depolarizing agent, veratridine (0.1 mM). In such experiments, the influx of
      (22)Na in SK-N-SH cells was only slightly altered by veratridine. Taken together,
      these data suggest that the morphologically undifferentiated human neuroblastoma
      cells are relatively inexcitable electrically. The iontophoretic application of
      acetylcholine to the cell body produced depolarizing responses whose amplitudes
      were dependent on the membrane potential.

PMID- 19604938
TI  - Effect of taurine, GABA and glutamate on the distribution of Na(+) and K(+) ions
      between the isolated synaptosomes and incubation medium.
AB  - Isolated synaptosomes of calf brain cortex lost 90% of their original Na(+)
      content and 70% of their K(+) content during 30 min incubation in Na(+)- and K(+)
      free iso-osmotic medium. Electrical stimulation, and 5 mmol/l of taurine or GABA
      significantly reduced the outflow of Na(+) and K(+) ions during incubation, but 5
      mmol/l of glutamate strongly increased their outflow. The effect of glutamate on
      ion outflow was slightly reduced by external electrical pulses.

PMID- 19604937
TI  - Changes of extracellular potassium activity in isolated spinal cord of frog under
      high Mg(2+) concentration.
AB  - Dorsal root potentials (DRPs) and changes of extracellular K(+) accompanying
      orthodromic stimulation were studied under high Mg(2+) concentration in isolated
      spinal cord of the frog. Under 20 mM MgSO(4) when synaptic transmission was
      blocked the amplitude of DRPs, evoked by a single volley in a dorsal root,
      decreased to 5-15% of the control and the transient increase of extracellular
      potassium concentration [K](e) evoked by 100 Hz orthodromic stimulation decreased
      to 10-15%. It is suggested that the DRPs, resistant to high Mg(2+) concentration,
      are produced by transient increase of K(+) that leaks from primary afferents.

PMID- 19604939
TI  - Amino acid inhibition of sodium-dependent synaptosomal proline uptake.
AB  - The inhibitory effects of several amino acids on the synaptosomal uptake of l
      proline were studied. Phenylalanine, valine, isoleucine and histidine were most
      inhibitory (I(50) approximately 100 muM) while leucine, serine and tyrosine had
      lesser inhibitory effects. The inhibition by phenylalanine and valine was of the
      competitive type. The inhibitory effects were stereospecific since d-isomers of
      the amino acids had no effect on synaptosomal proline uptake. The uptakes of
      three other putative neurotransmitter amino acids, viz. aspartic acid, glutamic
      acid and gamma-aminobutyric acid, were not similarly affected by the amino acids
      and the inhibitory effects thus appear to be unique to proline uptake. These
      results raise the possibility that the uptake of proline at the nerve endings may
      be regulated by the amino acids.

PMID- 19604940
TI  - Does adenosine participate in the mechanism of spreading depression?
AB  - It is known that depolarization of cortical cells in vivo during cortical
      spreading depression (CSD) is accompanied by accumulation of cyclic AMP (cAMP).
      Under similar conditions in vitro adenosine release has been demonstrated. The
      present study investigates the possible role of adenosine in the mechanism of
      CSD. Topically applied adenosine penetrated the cortical tissue and induced
      enhancement of cAMP levels up to 70% above control, but failed to elicit CSD.
      Threshold of K(+) to evoke CSD was not affected by adenosine. No EEG or slow
      potential changes were produced by adenosine. Thus adenosine does not seem to
      play an active role in the mechanism of CSD.

PMID- 19604941
TI  - Effects of hippocampal and lateral hypothalamic electrical stimulation on
      hippocampal cholinergic mechanisms in BALB/c inbred mice.
AB  - Electrical stimulation of the hippocampus (HPC) and of the lateral hypothalamus
      (LH) were found to have the same 24 h delayed effect on choline acetyltransferase
      activity. Since previous experiments demonstrated that these treatments had the
      same effect on memory storage processes, the present finding and earlier
      neurochemical investigations suggest that HPC and LH stimulation might act
      through a common hippocampal cholinergic mechanism.

PMID- 19604942
TI  - Circadian variations in cholinergic enzymes and muscarinic receptor binding in
      human cerebral cortex.
AB  - The cholinergic enzymes, choline acetyltransferase and acetylcholinesterase, and
      the muscarinic cholinergic receptor binding, measured in autopsy human brain,
      undergo significant variations in activity which are related to the time of
      death. Although certain similarities between the circadian rhythms are apparent,
      there is some evidence that the amplitude and phases of the changes in the three
      cholinergic components differ. It is suggested that the interrelationships
      between the circadian phases of the cholinergic system may be of importance in
      disorders of cerebral function and that circadian variation is a significant
      factor in the study of post-mortem brain biochemistry.

PMID- 19604943
TI  - Brain catecholamines and adrenocortical activation by morphine in the cat.
AB  - Following the administration of 250 mg/kg of alpha-methyl-p-tyrosine (H 44/68) to
      adult cats, an increase in plasma cortisol was found before any decrease in the
      contents of noradrenaline in the diencephalon could be observed; this suggests
      that the induced release of ACTH by H 44/68 administration may be independent of
      the synthesis impairment of catecholamines. The results observed in cats treated
      with H 44/68 plus morphine, suggest that the opioid causes an increase in the
      turnover of noradrenaline. Although different mechanisms for the action of
      morphine on the pituitary-adrenal system and on brain catecholamines cannot be
      ruled out, the increased secretion of ACTH induced by morphine could be related
      to the increased turnover of noradrenaline observed in this study.

PMID- 19604944
TI  - Effect of dopamine on the hypothalamo-pituitary-adrenocortical system after
      injection in the nucleus raphe dorsalis.
AB  - Dopamine (DA) injected into the dorsal raphe nucleus (DRN) increased plasma
      corticosterone (PCS) level as well as serotonin (5-HT) content in the
      mesencephalon and hippocampus 30 min after the administration. At the same time,
      5-HT content of the hypothalamus was decreased. A stress applied 2 min after the
      injection elevated PCS level but diminished hypothalamic 5-HT content in control,
      but not in DA-treated animals. PCS level and 5-HT content of the hypothalamus in
      DA-treated + stressed animals did not differ from the values found in DA-treated
      rats, but mesencephalic and hippocampal 5-HT content did not increase. It is
      concluded that DA injected into the DRN suppresses the response to stress of the
      hypothalamo-pituitary-adrenocortical system.

PMID- 19604945
TI  - Decreased responsiveness to low doses of apomorphine after dopamine agonists and
      the possible involvement of hyposensitivity of dopamine 'autoreceptors'.
AB  - Apomorphine in low dosage (0.3 mg/kg) inhibits climbing behavior, a stereotyped
      motor activity, in mice. Pretreatment with apomorphine in low doses (0.125 or
      0.25 mg/kg) or with piribedil (25 mg/kg), a weak dopamine agonist, results in a
      less marked inhibitory effect of the test dose of apomorphine. Apomorphine in low
      dosage or piribedil are also able to antagonize the increase in striatal
      homovanillic acid elicited by treatment with gammabutyrolactone. Thus, low
      stimulation of dopamine receptors can regulate the synthesis and release of
      dopamine even in the absence of impulse flow in dopaminergic neurons, and the
      initial stimulation of the receptors mediating such effects may lead to a state
      of hyposensitivity to further stimulation. The hypothesis that such receptors are
      autoreceptors is discussed.

PMID- 19604947
TI  - Serotonin and sexual behaviour in female rats. Effects of hallucinogenic
      indolealkylamines and phenylethylamines.
AB  - The effects of a number of hallucinogenic indolealkylamines and phenylethylamines
      on sexual receptivity in female rats have been studied. Preliminary experiments
      on extensor reflexes (which are highly dependent on serotonin (5-HT) receptor
      activity) indicated that the drugs possess marked 5-HT receptor agonist
      properties. All compounds increase sexual receptivity in low doses but inhibit
      this behaviour in high doses. 5-HT neurones are known to subserve inhibitory
      mechanisms in the control of receptivity. We suggest that the 5-HT agonists used
      enhance receptivity by preferentially stimulating presynaptic 5-HT receptors and
      inhibit receptivity by stimulating postsynaptic 5-HT receptors.
      Microiontophoretic and microelectrode recording data consistent with this
      hypothesis are discussed.

PMID- 19604946
TI  - Dopamine and sexual behaviour in female rats. Effects of dopamine receptor
      agonists and sulpiride.
AB  - The effects of dopamine (DA) agonists apomorphine, ET495, CB154 and Lergotril on
      the sexual receptivity of ovariectomized, oestrogen-treated rats was studied. In
      low doses all drugs caused a marked increase in receptivity, but as the dose
      increased the facilitatory effects disappeared; indeed, the highest doses of each
      drug inhibited oestrogen/progesterone-induced receptivity. We suggest the
      explanation for these effects to be selective presynaptic DA receptor stimulation
      by the agonists at low doses while, at high doses, postsynaptic DA receptor
      stimulation is the dominant effect. Consistent with this view was the fact that
      sulpiride, a putative presynaptic DA receptor blocker, prevented the effects of
      low but not high doses of the agonists. These data support the concept of an
      inhibitory role for DA neurones in the control of sexual receptivity.

PMID- 19604948
TI  - The inhibitory effect of methergoline on LAE-32-induced head-twitches in mice.
AB  - Methergoline (a selective 5-HT blocker) was more powerful than chlorpromazine in
      inhibiting LAE-32-induced head-twitches in mice. Suggestions are made regarding
      the possible antihallucinogenic effect of this drug.

PMID- 19604949
TI  - Effect of methergoline on body temperature in mice.
AB  - Serotonin (5-HT) involvement in body temperature regulation has been studied in
      mice by means of a 5-HT-selective blocking agent (methergoline). This drug causes
      an effect on body temperature which is dependent on environmental temperature. At
      environmental temperatures of 25 degrees C and 11 degrees C methergoline has a
      hypothermic effect, while at 36 degrees C environmental temperature, methergoline
      has a hyperthermic effect. At 25 degrees C environmental temperature, the
      hypothermic effect induced by 125 mug/kg i.p. of methergoline could be
      antagonized by low doses of LAE-32 (80 mug/kg s.c.), while there was not such an
      antagonism using higher doses of LAE-32 (100 and 300 mug/kg s.c.). This has been
      explained using Jalfre's hypothesis of the existence of 5-HT inhibitory and
      excitatory receptors.

PMID- 19604950
TI  - Alpha EEG asymmetry and speed of left hemisphere thinking.
AB  - Mental activity which engages one half of the brain is usually accompanied by a
      suppression of alpha rhythm that is greater over the active hemisphere. When the
      left hemisphere is active, as during mental arithmetic, the magnitude of the
      asymmetry in the alpha rhythm is proportional to the rate at which subjects
      perform their calculations.

PMID- 19604951
TI  - Exuberant projection into the corpus callosum from the visual cortex of newborn
      cats.
AB  - In the first postnatal week, neurones projecting into the corpus callosum can be
      identified in kitten's visual cortex by retrograde transport of HRP. The neurones
      are located in layers III, IV, and VI. The region of cortex which gives rise to
      the callosal projection extends beyond its adult boundaries over most of area 17,
      18, 19 and in the suprasylvian sulcus.

PMID- 19604952
TI  - The convergence of sympathetic preganglionic fibres on vasomotor neurones of the
      ganglia in lumbar sympathetic chain.
AB  - By means of intracellular recordings from the neurones of isolated L(3)-L(6)
      ganglia it was shown that B(1)-, B(2)- and C-preganglionic fibres widely converge
      on these neurones. Besides, a part of the ganglionic neurones is activated by
      slow-conducting C-fibres coming into the ganglia through the grey rami.
      Identified vasomotor neurones have the distinctive feature of preganglionic fibre
      convergence. Only B(2)- and C-preganglionic fibres were able to activate them,
      but the efficacy of the B(2)-fibre excitatory action is considerably higher.

PMID- 19604953
TI  - Phase-dependent transmission in the excitatory propriospinal reflex pathway from
      forelimb afferents to lumbar motoneurones during fictive locomotion.
AB  - In high spinal paralyzed cats the effect of forelimb nerve stimulation on
      hindlimb motoneurones was investigated during fictive locomotion, which was
      induced by injection of nialamide and L-DOPA. The EPSPs which were evoked by
      forelimb nerve stimulation in almost all species of hindlimb motoneurones showed
      a distinct dependence on the phase of the step cycle. In motoneurones to extensor
      they were only observed during the extension phase, in those to flexors only
      during the flexion phase. It is assumed that the transmission in the descending
      propriospinal excitatory reflex pathway is cyclically modulated at the lumbar
      level.

PMID- 19604954
TI  - Climbing fibre activation of cerebellar purkinje cells in unanaesthetized,
      unrestrained cats.
AB  - A comparison has been made between the number of spikes in the complex spikes of
      cerebellar Purkinje cells and the number of climbing fibre impulses which underly
      these responses in unanaesthetized cats. No exact relationship was detected
      between these events but the data strongly suggest that multiple-spiked complex
      spikes can be generated by a single climbing fibre impulse.

PMID- 19604955
TI  - Intracellular recording from hypothalamic neurosecretory cells in tissue culture
      (clone HT9-C7).
AB  - Electrophysiological and pharmacological studies have been performed on a clone
      of mouse hypothalamic neurosecretory cells synthesizing neurophysin and
      vasopressin (HT9-C7). These neurons possessed low resting membrane potential
      (RMP) and weak membrane resistance (MR). They did not exhibit spontaneous
      activity. Electrical stimulation or microiontophoretic application of putative
      neurotransmitters did not induce action potentials. Nevertheless, dopamine and
      gamma-aminobutyric acid appeared to exert a slight hyperpolarizing effect on RMP.
      Radioimmunoassays, carried out on the culture medium after electrical
      stimulation, did not reveal any measurable quantities of vasopressin. However, an
      electron microscopic analysis of the cytoplasmic processes of these cells did not
      reveal axonal outgrowth. It can be assumed that the weak electrophysiological and
      pharmacological properties of these neurons have to be related to their weak
      morphological differentiation. Two hypotheses might account for the absence of
      most characteristics of in situ magnocellular hypothalamic neurons in HT9-C7
      cells: the lack of pituicytes, the target cells for the axon terminal of
      magnocellular neurons, and the SV40 transformation itself which may impede
      neuronal maturation.

PMID- 19604956
TI  - Potassium effect on Na(+), K(+)-ATPase activity of cultured newborn rat
      astroblasts during differentiation.
AB  - High K(+) concentration effect on Na(+), K(+)-ATPase activity of cultured newborn
      rat astroblasts has been studied in conditions under which astrocytic
      differentiation could have taken place. In 14-day-old cultures, no potassium
      effect could be found reflecting the undifferentiated state of these cultures.
      After dibutyryl-cyclic AMP treatment, which induces a morphological
      transformation suggesting a differentiation, no K(+) effect appears but the
      specific enzyme activities are higher than in control cells reflecting the
      development of numerous cellular processes. After 28 days of cultivation - a
      cultivation period which closely corresponds to the time of astrocytic
      differentiation in vivo - Na(+),K(+)-ATPase activity at 25 and 50 mM K(+)
      concentrations are higher than at 10 mM, suggesting that an astrocytic
      differentiation has taken place in vitro.

PMID- 19604957
TI  - A low pH form of thiamine pyrophosphatase from bovine brain.
AB  - A preparation of thiamine pyrophosphatase from bovine brain exhibits an activity
      optimum at pH 6 and only sight activity is observed at pH 9-9.5. This low pH form
      of thiamine pyrophosphatase gives maximal activity with Mn(2+). Other divalent
      cations (Mg(2+), Ca(2+) and Co(2+) also satisfy the divalent cation requirement,
      but give loss activation than Mn(2+). The low pH form of thiamine pyrophosphatase
      has not been previously observed independent of the high pH form. The data
      suggest that thiamine pyrophosphatase occurs in two separate enzyme forms in
      brain tissue.

PMID- 19604958
TI  - Structural changes in cerebral cortex during cobalt-induced epilepsy in the rat.
AB  - Rods of cobalt metal were inserted into rat cerebral cortex to produce
      experimental epilepsy. Brain sections were then stained and examined for
      structural changes at several survival times. Times were based on previous
      electrocorticographic studies. Comparisons were made with tissue from rats
      implanted with non-epileptogenic copper or glass rods. Gliosis was much more
      extensive after copper than after cobalt. Silver-staining revealed unusual , dark
      granules associated with neurons only in the cobalt-treated rats. Three weeks
      after cobalt treatment, enlarged perikarya were observed around the implant. The
      possible significance of these findings is discussed.

PMID- 19604959
TI  - Effect of clonidine (catapresan, St-155) on sympathetic reflexes.
AB  - The effect of clonidine on sympathetic vasomotor reflexes elicited by electrical
      stimulation of visceral and somatic nerves was studied. Clonidine was proved to
      shift the sympathetic vasomotor reflex processes towards excitation.

PMID- 19604960
TI  - The effects of unilateral 6-hydroxydopamine lesions in the substantia nigra on
      hippocampal noradrenaline-induced feeding and other behaviour in the rat.
AB  - The latency, duration of feeding and number of feeding periods recorded from rats
      after noradrenaline injection to the hippocampus show little change after
      unilateral 6-hydroxydopamine injections to the substantia nigra. It is suggested
      that 6-hydroxydopamine-induced weight losses result from non-specific effects of
      injection because increased durations for grooming, decreased latencies for
      resting and short periods of feeding follow injection.

PMID- 19604961
TI  - Amino acid uptake required for long-term memory formation.
AB  - alpha-Amino-iso-butyrate (AIB) inhibits long-term, protein synthesis-dependent
      memory formation by reducing labelled leucine uptake in vivo without affecting
      leucine incorporation into protein. Unlike the antibiotic cycloheximide, AIB does
      not block long-term memory formation through inhibition of protein synthesis per
      se. The behavioural effect of AIB is restricted to times of administration
      between 5 min before and 5 min after learning a single trial passive avoidance
      task by day-old chickens. It is concluded that (1) AIB competes with normal amino
      acids for uptake into cells, and (2) the uptake of amino acids for protein
      synthesis specific to long-term memory formation takes place in the first few
      minutes following learning.

PMID- 19604962
TI  - Analysis of collateral projections with a double retrograde labeling technique.
AB  - A method is described whereby collateral innervation by a single cell type may be
      determined by double retrograde labeling with horseradish peroxidase (HRP) and
      tritiated bovine serum albumin ([(3)H]BSA). The projections from the entorhinal
      area to the hippocampal formation were analyzed as a model system, since layer
      III pyramidal cells project bilaterally to the hippocampus. Following HRP
      injections into the hippocampus of one side, and [(3)H]BSA injections into the
      opposite hippocampus, double labeled cells were found in layer III of the
      entorhinal cortex. These doubly labeled cells could best be viewed in plastic
      embedded material, whereas frozen sections were found to be inadequate for
      clearly distinguishing between silver grains and HRP reaction product.

PMID- 19604963
TI  - Differential sensitivity between blue and brown reaction procedures for HRP
      neurohistochemistry.
AB  - Four rhesus monkeys and two rats were injected with horseradish peroxidase (HRP).
      Adjacent sections were stained with a 3,3'-diaminobenzidine tetrahydrochloride
      (DAB) and a benzidine dihydrochloride (BDHC) procedure which yields a blue
      reaction product at sites of HRP activity. The number of labeled neurons was
      counted within the same regions of the adjacent sections with bright-field and
      dark-field illumination. Sections processed with the BDHC procedure consistently
      contained more labeled neurons than adjacent sections processed with a
      representative DAB procedure. Such differences were observed in cortical as well
      as subcortical areas and in the monkey as well as in the rat. Moreover, the
      visibility of labeled neurons under bright-field illumination was quite superior
      in the tissue stained with the BDHC procedure. It is concluded that the BDHC
      procedure is more sensitive than a DAB procedure for the demonstration of the
      retrograde transport of HRP. In additional experiments tetramethyl benzidine
      (TMB) was used in place of BDHC and comparable results were obtained.

PMID- 19604964
TI  - Subcellular fractionation of rapidly transported axonal material in olfactory
      nerve: evidence for a size- dependent molecule separation during transport.
AB  - [(3)H]Leucine applied to the olfactory mucosae of garfish pike results in rapid
      precursor uptake, incorporation into proteins and export of labeled protein by
      axoplasmic transport. The resulting characteristic isotope distributions along
      the nerve have been subjected to subcellular fractionation. More label is found
      associated with the particulete fraction obtained from the most rapidly moving
      profile region than from the regions produced by more slowly moving material. The
      smaller material tends to separate from the larger molecular complexes by
      trailing behind. The results are discussed in relation to the transport
      mechanism.

PMID- 19604965
TI  - The ultrastructure of the large granular vesicles of the frog's habenula.
AB  - Two types of large granular vesicles in the habenular nuclei of the frog Rana
      esculenta following aldehyde fixation are described. One type is almost
      completely filled by a dense droplet. The other type contains a globular
      substructure. Both satisfy the morphological criteria for neurosecretory
      granules.

PMID- 19604966
TI  - The distribution of enkephalin-immunoreactive cell bodies in the rat central
      nervous system.
AB  - With the indirect immunofluorescence technique the distribution of methionine
      enkephalin-immunoreactive cell bodies was studied in the central nervous system
      of rats pretreated with colchicine. The antiserum used did cross-react to 10%
      with leucine-enkephalin but to less than 0.1% with alpha-, beta-, and gamma
      endorphine. Cell bodies with a specific immunofluorescence were observed in the
      tel-, di-, mes- and rhombencephalon and in the spinal cord.

PMID- 19604967
TI  - Postnatal growth of neuronal perikarya in the dorsal lateral geniculate nucleus
      of the rat.
AB  - The cell bodies of relay neurons in the dorsal lateral geniculate nucleus of the
      rat achieve their adult size 16 days after birth, the greatest increases occuring
      between days 4-6 and days 14-15. Perikarya of intrinsic neurons continue to grow
      up to at least day 20. Perikaryal growth and the growth and maturation of the
      dendritic tree of relay neurons are synchronous.

PMID- 19604968
TI  - An electrophysiological investigation of the projection of the intramedullary
      primary afferent cells of the lamprey ammocoete.
AB  - The intramedullary dorsal cells, whose peripheral processes form primary
      afferents, were identified in the lamprey ammocoete and were antidromically
      invaded by stimulation of their rostrally projecting intraneuraxial axons. Twenty
      five out of 33 cells were found to project to the isthmus; conduction velocity
      was found to decrease in a rostral direction, suggesting that numerous collateral
      branches are given off as the axon ascends through the cord and brain stem.

PMID- 19604969
TI  - Bilateral projection of nigro-collicular neurons: An electrophysiological
      analysis in the rat.
AB  - In response to stimulation of the deep layers of the superior colliculus (SC) in
      the rat, nigral neurons were antidromically activated (latency 0.5-1.5 msec).
      Effective stimulations were located in ipsi- or contralateral SC deep layers
      lying above the central gray (CG) or more laterally; nigro-collicular neurons are
      exclusively located in the pars reticulata of the substantia nigra (SN) and some
      of them project both to ipsi- and contralateral SC. The functional significance
      of this nigral projection is discussed.

PMID- 19604970
TI  - Is light receptor a dipole? Electrophysiological study in an arachnid.
AB  - Retinal action potential (RAP) was recorded at different depths in the median eye
      of scorpion, using a glass micropipette electrode (tip diameter 2-3 mum). The
      amplitude of RAP was largest when the tip of the electrode touched the distal
      process of the receptor cell (RC). The polarity of RAP became reversed when the
      tip was inside the cell body. It is suggested that RC acted as a dipole with the
      outer segment being the current sink and the cell body, the source. This
      situation is similar to the findings in the light receptors of insects,
      crustaceans, molluscs and also in vertebrate retina.

PMID- 19604971
TI  - A simple method of cross-correlating spike trains demonstrated on primary muscle
      spindle ending discharges.
AB  - A simple method is shown by which spike trains can be correlated. It is based on
      the Parzen convolution estimation and can easily be implemented with some
      electronic hardware and an averaging computer. The method is demonstrated on
      spike trains from primary muscle spindling endinga. Advantages and drawbacks are
      discussed.

PMID- 19604973
TI  - Neuronal activity correlated with eye movement in the cat's pretectum.
AB  - Single unit activity correlated with horizontal and vertical saccades was
      recorded in darkness from n. pretectalis anterior (NPA), n. pretectalis olivaris
      (NPO), n. tractus opticus (NTO) and n. pretectalis posterior (NPP). The units
      studied fell into two classes. The first class neurons displayed a high frequency
      burst of activity prior to the onset of a saccade regardless of where the eye was
      when the movement started. These neuronal reponses, mainly recorded from NPA and
      NPO, can therefore be ascribed to the motor aspect of the eye movement. The
      second type units, mostly found in NPP and NTO, responded after the initiation of
      a saccade and might be ascribed to a postsaccadic facilitation related to the
      visual attention during the fixation period.

PMID- 19604972
TI  - Cross-correlations between discharge patterns of primary muscle spindle endings
      in active triceps-surae muscles of the cat.
AB  - Cross-correlations were computed between simultaneously recorded spike trains
      from primary spindle endings lying in variably active triceps-surae muscles of
      decerebrate cats. The discharge patterns of these primary endings were rather
      frequently correlated, the correlation function usually resembling that for
      nearly synchronous firing. This feature is most often particularly pronounced in
      closely neighbouring spindles. After light curarization, cross-correlations are
      generally diminished, but not always abolished completely, suggesting a still
      existing correlating influence of gamma motoneurones. Deep curarization or
      deefferentation abolishes significant features in the cross-correlograms.

PMID- 19604974
TI  - Evidence for a nerve impulse-dependent GABA accumulation in the substantia nigra
      after treatment with gamma-glutamylhydrazide.
AB  - GABA accumulation was studied in the substantia nigra after treatment with L
      glutamic acid-gamma-hydrazide (GAH) in rats 3 h following hemisection at the
      posterior hypothalamic level. GAH-induced GABA accumulation was significantly
      reduced on the hemisectioned side (P < 0.05, Wilcoxon's test). Two or three weeks
      after hemisection, glutamic acid decarboxylase activity was reduced in the
      substantia nigra of the hemisectioned side by 80%, showing that the descending
      GABA pathway to the substantia nigra had been transected. It is concluded that
      GAH-induced GABA accumulation might be nerve impulse-dependent.

PMID- 19604975
TI  - On the catecholamine control of growth hormone regulation. Evidence for discrete
      changes in dopamine and noradrenaline turnover following growth hormone
      administration.
AB  - Two hours following treatment with rat growth hormone (100 mug/kg, i.v.) a
      reduction of noradrenaline (NA) levels in the rat's hypothalamic subependymal
      layer was observed. Further findings indicate a reduction of dopamine (DA)
      turnover in the medial and lateral palisade zone of the median eminence and of NA
      turnover in the posterior perinventicular hypothalamic region. This suggests thee
      existence of a facilitory noradrenergic mechanism in the posterior
      periventricular hypothalamic region facilitating growth hormone secretion and
      that of an inhibitory dopaminergic mechanism in the medial palisade zone
      inhibiting the secretion of somatostatin.

PMID- 19604976
TI  - Is there a correspondence between half-lives of motor endplate
      acetylcholinesterase and junctional acetylcholine receptors?
AB  - In order to study the turnover rate of motor endplate acetylcholinesterase
      (AChE), we have treated hypoglassal nerve with 10 mM colchine, a drug that
      produced a reversible decrease of AChE from geniohyoid muscle endplates. The
      return of AChE to the normal steady-state level has been used to calculate an
      AChE half-life of 4.6 days. This value is very close to that obtained for the
      half-life of junctional acetylcholine receptors (AChR). Our result supports the
      contention that both macromolecules have the same turnover rate.

PMID- 19604977
TI  - Diurnal oscillation of choline acetyltransferase activity in human blood.
AB  - The present study reports on the diurnal variation of choline acetyltransferase
      (ChAT; EC 2.3.1.6.) activity observed in human blood. The product of the
      enzymatic reaction, acetylcholine, was identified by thin-layer chromatography.
      The oscillation, first found in the blood of a male volunteer, was confirmed in
      the blood of a man and a woman volunteers during several days. The maximum enzyme
      activity appeared to be localized in the afternoon hours and the minimum in the
      morning hours. Similar results were found on several volunteers of both sexes who
      showed a statistically significant difference in ChAT activity between 11:30 and
      18:30 h. No statistically significant sexual differences was observed. The
      results are related to the diurnal oscillation of the cholinergic system in rat
      brain and would indicate a cellular localization of the rhythm.

PMID- 19604978
TI  - Staining of the dorsal root projection to the cat's dorsal horn by anterograde
      movement of horseradish peroxidase.
AB  - A modification of the horseradish peroxidase method was used to stain selectively
      dorsal root fibers entering the spinal cord of the cat. This technique stains
      intact terminal arborizations. Using this method to examine the primary afferent
      supply to lamina II of the lumbosacral segments, we observed that both thick
      primary afferent collaterals (2-3 mum), entering by way of the dorsal column, and
      thinner primary afferent collaterals (<1 mum), entering by way of Lissauer's
      tract, form terminals in lamina II. The terminals derived from the thick primary
      afferent collaterals were concentrated in the ventral portion of lamina II.

PMID- 19604979
TI  - Perihypoglossal and secondary vestibular projections to lobules VI and VII of the
      cerebellar cortex: An HRP study.
AB  - Horseradish peroxidase (HRP) was injected into (1) lobule VI; (2) lobule VII; (3)
      lobule VI and VII of the cat's cerebellar vermis. Marked cells were found in two
      groups of nuclei related to the vestibulo-ocular system; (a) the three
      perihypoglossal nuclei: praepositus hypoglossi, nucleus of Roller and
      intercalatus of Staderini and (b) two areas of the secondary vestibular complex
      located within the medial and the descending vestibular nuclei. It is concluded
      that fibers from the perihypoglossal and the secondary vestibular nuclei project
      to both lobule VI and lobule VII of the cerebellar cortex.

PMID- 19604980
TI  - Experimental demonstration of intrinsic synapses in cat's caudate nucleus.
AB  - The electron microscopic findings in cats after complete interruption of all
      afferents to caudate nucleus as well as of its efferent fibers, suggest that the
      type IX synapses, the presynaptic component of which contains large empty round
      vesicles, are formed by the axon terminals of intrinsic neurons. They make
      synaptic contacts with the dendrites or soma of the large efferent striatal
      neurons. All other types of synapses, except many of the pleomorphic type V which
      are probably formed by axon collaterals of the efferent neurons, degenerated in
      these experiments.

PMID- 19604981
TI  - Immunocytochemical and ultrastructural identification of luteinizing hormone
      releasing hormone (LH-RH)-containing neurons in the vascular organ of the lamina
      terminalis (OVLT) of the squirrel monkey.
AB  - By comparison of immunocytochemical data and classical electron microscopic
      results, luteinizing hormone-releasing hormone (LH-RH)-immunoreactive neurons are
      described in the vascular organ of the lamina terminalis (OVLT) of the squirrel
      monkey. These cells contain neurosecretory granules (NSG) essentially located at
      their periphery. The rough endoplasmic reticulum and the Golgi apparatus are well
      developed. Some NSG are also associated with the Golgi complex. Nerve endings
      containing NSG are observed at the surface of the ependymocytes.

PMID- 19604982
TI  - Presynaptic dendrites in the cuneate nucleus of the monkey (macaca fascicularis).
AB  - Presynaptic dendrites (PSDs) are described in the cuneate nucleus of the monkey.
      These PSDs establish dendro-dendritic synapses with dendrites of variable size.
      They contain small numbers of pleomorphic synaptic vesicles which are clustered
      together near the presynaptic membrane. Such PSDs have also been observed to be
      postsynaptic to medium-sized or large axon terminals containing round vesicles.

PMID- 19604983
TI  - Functional maturation of rat trigeminal nerve.
AB  - By investigating the relative number of activated axons per microelectrode track,
      the conduction velocities and the recovery periods, it is shown that the
      maturation of the maxillary branch of the rat trigeminal nerve is mainly
      postnatal and continues well after the third postnatal week. An unexpected
      ongoing activity is found to occur in this maturing sensory nerve. This sustained
      activity decreases as the animals grow older. It cannot be suppressed by
      prolonged peripheral sensory deprivation, thus suggesting a local (endogenous)
      origin. It can be suppressed by cooling the nerve. This suppression seems to have
      effects on the functional capabilities of the nerve.

PMID- 19604984
TI  - Epinephrine localization in human brain stem.
AB  - A study was undertaken to determine the presence and possible localization of
      epinephrine (E) in the human brain stem. Three brain stems were analyzed,
      although detailed mapping was performed only on the third. E was found to be
      highly localized in the reticular formation and the aqueductal gray. The highest
      concentrations were found in the region of the floor of the fourth ventricle.
      Norepinephrine (NE) and dopamine (DA) determinations were included in the
      analyses. These catecholamines were also found to be localized in the same
      regions. The relative E concentrations ranged from about 1-10% of the total
      catecholamine content.

PMID- 19604986
TI  - Long-term cell culture of electrically active sensory neurons free of glial
      cells.
AB  - A method has been devised for long-term culturing of sensory ganglion cells, free
      of non-neuronal cells. After enzymatic-mechanical disaggregation of embryonic
      chick sensory ganglia the cell suspension is plated in dispersed cell culture.
      After 2-3 weeks in culture neurons and satellite cells re-associate in a
      histiotypic fashion. Partial or complete elimination of non-neuronal cells is
      achieved by treatment of the cultures with fluorodeoxyuridine. The glia-deprived
      neurons are electrophysiologically active and can be maintained in cell culture
      for more than 5 months.

PMID- 19604985
TI  - Location and conduction velocity of raphespinal neurones in nucleus raphe magnus
      and raphe pallidus in the cat.
AB  - Extracellular recordings were made from raphespinal neurones identified by
      antidromic stimulation of their axons in the upper lumbar cord. Conduction
      velocities ranged from 1.25 to 67 m/sec. Neurones with axonal conduction
      velocities of 1.25-5 m/sec were found mainly ventrally, in nucleus raphe
      pallidus; many of these are presumably tryptaminergic cells with unmyelinated
      axons. In nucleus raphe magnus most raphespinal neurones had axonal velocities
      between 7 and 67 m/sec; these axons must be myelinated. This indicates that most
      raphespinal neurones in nucleus raphe magnus are non-tryptaminergic, and it is
      suggested that analgesia mediated by raphespinal neurones may not be solely due
      to the action of 5-hydroxytryptamine descending systems.

PMID- 19604987
TI  - Synthesis of cerebrosides by intact oligodendroglia maintained in culture.
AB  - Oligodendroglia, isolated in bulk from dissected white matter from lamb brain,
      can now be maintained in culture. The cells actively synthesize both cerebrosides
      and sulfatides, lipids found concentrated in myelin, as well as other myelin
      components. Thus this provides a useful model to study myelin assembly in vitro.

PMID- 19604988
TI  - Slow release of transmitter at the squid giant synapse.
AB  - The giant synapse of the squid was tested with small amplitude, long-lasting
      depolarizations applied to the presynaptic terminal. The presynaptic potential at
      which transmitter release could be detected was only a few millivolts more
      positive than the resting potential, and much less positive than the 'threshold'
      for transmitter release by a brief (<1 msec) depolarizing pulse. Onset and
      termination of this low-level release were very slow.

PMID- 19604989
TI  - Interlaminar differences in the effects of early and late monocular deprivation
      on the visual acuity of cells in the lateral geniculate nucleus of the cat.
AB  - Visual acuity of single cells in the lateral geniculate nucleus (LGN) of normal
      cats is significantly higher in lamina A than in lamina A(1). After early
      deprivation, visual acuity is impaired in both deprived laminae [5]. Reverse
      closure and forced usage of the early deprived eye leads to a partial recovery of
      visual acuity. Recovery is more obvious in the LGN contralateral to the early
      deprived eye than in the ipsilateral LGN. Late deprivation effects are merely
      observed in the A(1) layers. In both hemispheres of reverse sutured cats the
      ratio of mean visual acuity of layer A to A(1) is larger than this ratio in
      normal cats.

PMID- 19604990
TI  - Anteroventral third ventricle periventricular ablation: Temporary adipsia and
      persisting thirst deficits.
AB  - Bilaterally symmetrical periventricular lesions at preoptic-anterior hypothalamic
      levels of anteroventral third ventricle (AV3V) produce adipsia without aphagia in
      the rat. Sweet palatable fluids, but not water, are drunk during the adipsic
      period and if hydration is thus maintained, voluntary ingestion of plain water
      returns within 10 days. After recovery of spontaneous water drinking, drinking
      evoked by peripheral angiotensin or hypertonic NaCl thirst challenges is
      depressed whereas drinking evoked by hypovolemia or feeding after deprivation are
      unaltered. These results demonstrate a critical role for AV3V in control of water
      intake, and support the hypothesis that AV3V neural elements function to
      transduce angiotensin and osmotic hydrational stimuli.

PMID- 19604991
TI  - Subfornical organ: Duration of dipsogenic action of angiotensin-II.
AB  - Prior evidence from our laboratory has implicated the subfornical organ (SFO) as
      a site of angiotensin-II (A-II)-induced drinking [22]. In the present study,
      animals were denied access to water for 0, 0.5 and 1.0 h following a single
      intracranial A-II injection into the SFO. Even after a delay of 1.0 h, A-II
      injected animals showed increased water consumption compared to controls. Animals
      injected with A-II and tested immediately consumed significantly more water than
      the 1 h delay animals. Potential mechanisms involved in the maintenance of the
      drinking effect of A-II after 1 h and the decreased drinking in 1.0 h relative to
      the 0 h group were considered.

PMID- 19604992
TI  - Spreading depression in hippocampus and neocortex of rats induced by ACTH(1-24).
AB  - Microinjection of synthetic ACTH(1-24) solution into the neocortex or hippocampus
      of anesthetized rats elicited waves of spreading depression in both structures.
      The average effective doses for eliciting spreading depression were 6.22 mug
      (range 2.5-15.0 mug) in neocortex and 1.38 mug (range 0.24-2.88 mug) in
      hippocampus. This suggests that some of the behaviors elicited by intracranial
      injection of ACTH may be due to hippocampal (and possibly also neocortical)
      spreading depression.

PMID- 19604993
TI  - l-2,4-Diaminobutyric acid and the GABA system.
AB  - The effects of l-2,4-diaminobutyric acid (DABA) on GABA levels and on the
      activity of GABA metabolizing enzymes have been studied in a number of rat brain
      regions after both acute and chronic administration. Kinetic studies indicated
      that DABA was a non-linear, non-competitive inhibitor of GABA transaminase
      activity. The DABA-induced elevation of GABA levels paralleled the inhibition of
      GABA transaminase activity. DABA was a more effective inhibitor of GABA
      transaminase in vivo than in vitro, and this inhibition probably produced the
      elevation of GABA levels. The neurotoxicity of DABA appears to produce a use in
      GABA replacement therapy.

PMID- 19604994
TI  - Diphenylhydantoin prolongs postsynaptic inhibition and iontophoretic GABA action
      in the crayfish stretch receptor.
AB  - The action of diphenylhydantoin (DPH) was studied in the crayfish stretch
      receptor on the IPSP evoked by efferent fibre stimulation and on the conductance
      and potential changes produced by local iontophoresis of GABA. DPH caused a
      prolongation of these transients. DPH prevented the blockade by picrotoxin of
      postsynaptic inhibition and of GABA responses. These findings suggest a
      postsynaptic site of action of DPH close to the GABA-mediated chloride
      conductance mechanism.

PMID- 19604995
TI  - Effects of methylene blue on transmission in autonomic ganglia.
AB  - In vivo perfusions with methylene blue of the cat's caudal mesenteric sympathetic
      ganglion gradually suppresses transmission in the ganglion, measured as an
      increase in latency and a decrease in amplitude of the compound action potentials
      in the postganglionic fibres.

PMID- 19604996
TI  - Effect of concanavalin A on the cholinergic responses of mouse neuroblastoma
      cells.
AB  - The surface properties of a clone of mouse neuroblastoma cells were modified by
      the use of concanavalin A that binds to these cells through specific interactions
      with saccharide-containing receptors. These receptors were found throughout the
      surface membranes of the cell body as well as the neurites of neuroblastoma
      cells. Neither resting nor action potentials were modified by treating the cells
      with concanavalin A (20-25 mug/ml) for 60 min at 35 degrees C. Instead,
      concanavalin A blocks the muscarinic response and possibly the nicotinic one to
      applied acetylcholine.

PMID- 19604997
TI  - On the mechanism of the acute decrease of rat brain tryptophan hydroxylase
      activity by 4-chloroamphetamine.
AB  - The decrease of rat brain soluble tryptophan hydroxylase activity 4 h after the
      injection of 20 mg/kg i.p. of 4-chloroamphetamine was antagonized by 20 mg/kg
      i.p. of zimelidine, a selective inhibitor of membrane serotonin (5-HT) uptake, by
      2.5 mg/kg i.p. of chlorpromazine and by 5 mg/kg i.p. of methergoline, a proposed
      antagonist of central 5-HT receptors, when these compounds were injected 15 min
      prior to 4-chloroamphetamine. Zimelidine partially reversed the fall in
      tryptophan hydroxylase when injected 4 h after 4-chloroamphetamine and the enzyme
      activity was recorded after further 4 h. Reserpine, 5 mg/kg i.p., 18 h before 4
      chloroamphetamine prevented the decrease of the enzyme activity but had no effect
      when injected 1 h beforehand. It is suggested that the decrease of the tryptophan
      hydroxylase activity is secondary to the release of 5-HT and mediated by 5-HT
      receptor stimulation.

PMID- 19604998
TI  - A long-term effect of an early stimulation of the lateral hypothalamus on the
      acquisition and extinction of a food reinforced operant conditioning in the rat.
AB  - Two experiments point out the effect of an early stimulation of the lateral
      hypothalamus on later behavior of rats. Stimulated at 15 days of age, animals
      showed an improvement in both acquisition of a food reinforced operant
      conditioning (two different proceedings) and extinction of this conditioning,
      studied during the sixth week of age. The results are discussed in terms of a
      high plasticity of the central nervous system at time of the stimulation.

PMID- 19604999
TI  - Brain stimulation reward: Evidence for an adrenergic contribution in the rat.
AB  - Two centrally active inhibitors of phenylethanolamine-N-methyltransferase (PNMT:
      E.C. 2.1.1.28), the terminal enzyme for epinephrine biosynthesis in the brain,
      and a centrally active blocker of adrenergic synapses produced dose-related
      decreases in responding for intracranial reward. These decreases occurred at
      dosage levels which were free from measurable neurologic impairment. The present
      findings may indicate a possible role for epinephrine-containing neurons in the
      control of central reward processes.

PMID- 19605000
TI  - A safer and more sensitive substitute for diamino-benzidine in the light
      microscopic demonstration of retrograde and anterograde axonal transport of HRP.
AB  - The commonly used benzidine derivatives such as diaminobenzidine, o-dianisidine
      and benzidine dihydrochloride are apparently carcinogenic. Available information,
      however, indicates that tetramethyl benzidine (TMB) is safer in this regard, and
      we have therefore developed a procedure in which TMB is used as a substrate for
      the detection of intra-axonal transport of HRP. The TMB procedure is simple,
      reliable and does not produce crystals if properly executed. The staining
      procedure, which takes about 15 min, produces a blue reaction product which is
      easily detected in bright-field microscopy.

PMID- 19605001
TI  - Vasoactive intestinal polypeptide and the nervous system: immunohistochemical
      evidence for localization in central and peripheral neurons, particularly
      intracortical neurons of the cerebral cortex.
AB  - Immunohistochemical studies on rat brain revealed large numbers of vasoactive
      intestinal polypeptide (VIP)-positive nerve cell bodies all over the limbic
      cortex and neocortex. Large numbers of nerve terminal plexus' were found within
      all layers of the limbic cortex, but mainly within layers II-IV of the neocortex.
      Thus, association neurons probably exist in the cerebral cortex which store VIP
      or VIP-like peptides, making possible a role for such peptides in higher nervous
      processes. A neuroendocrine function may also be postulated in view of the
      presence of VIP-positive terminals in the central amygdaloid nucleus,
      suprachiasmatic nucleus, medial preoptic nucleus and the anterior hypothalamic
      nucleus.

PMID- 19605002
TI  - A method for sectioning microwave-fixed brain prior to microdissection and
      acetylcholine analysis.
AB  - Before proceeding with a detailed study of acetylcholine (ACh) distribution in
      the rat brain, a method was needed to make 300 microm brain sections for
      microdissection. We found cryostat sections of microwave-irradiated brains to be
      of poor quality, with rough surfaces and cracks. The use of a vibratome resulted
      in smooth, intact sections. This technique requires that unfrozen tissue be
      immersed in liquid during sectioning. Krebs-Ringer buffer or an inert
      fluorocarbon liquid (FC-47) were used for such sectioning. ACh was measured in
      forebrain regions from cryostat sections and vibratome sections cut in buffer or
      FC-47. Diffusion of ACh was apparent after sectioning in buffer, but not in FC
      47. Vibratome sectioning in FC-47 should facilitate study of the distribution of
      ACh and other labile substances in rat brain.

PMID- 19605003
TI  - Solitary membrane associated particles in normal and experimentally enlarged
      synaptic vesicles.
AB  - Freeze-etch replicas of synaptic vesicles were obtained from the vertebrate
      central nervous system and from the frog motor endplate. Large solitary particles
      were found to be associated mainly to the cytoplasmic fracture face of the
      vesicle membrane. They are especially conspicuous in the initial stages of
      Wallerian degeneration when the synaptic vesicles are abnormally large. The
      finding of these particles bears a striking resemblance to the previous
      observations of cytochemically verified vesicular calcium binding sites. The
      possible role of these particles for control by Ca(2+) of transmitter release is
      discussed.

PMID- 19605004
TI  - Relation of motor cortex neurons to precisely controlled and ballistic movements.
AB  - A visual pursuit-tracking paradigm was used for training monkeys to position a
      handle within a small zone and rotate it by pronation-supination movements. Motor
      cortex unit discharge was examined in relation to movements carried out in this
      situation, with particular attention to large ballistic movements as compared to
      small precisely controlled movements. Intense unit discharge was found to occur
      with even the smallest movements made to achieve accurate positioning of the
      handle. Within the group of motor cortex pyramidal tract neurons (PTNs), slowly
      conducting tonically discharging PTNs showed the most selective relations to
      these small precisely controlled movements.

PMID- 19605005
TI  - Sensory responses in motor cortex neurons during precise motor control.
AB  - Precentral neurons whose activity changed with precisely controlled small
      supination-pronation movements almost invariably showed sensory responses to
      small perturbations which pronated or supinated the forearm in conscious monkeys.
      Conversely, most units failing to show changes with small movements but being
      recruited with large ballistic movements were unaffected by these kinesthetic
      inputs. Moreover, perturbations which yielded intense short-latency unit
      responses when delivered during postural stability usually failed to modify unit
      activity when delivered during a ballistic movement. It is suggested that sensory
      feedback continuously modulates motor cortex neuron discharge during accurate
      positioning and precise fine movement, whereas during ballistic movements such
      modulation is greatly attenuated.

PMID- 19605006
TI  - Functional localization in the rabbit's cerebellar flocculus determined in
      relationship with eye movements.
AB  - In alert albino rabbits, the cerebellar flocculus was mapped for the effect of
      its local stimulation upon eye movements. Stimulation through a glass pipette
      electrode placed in a relatively rostral area induced abduction of the
      ipsilateral eye. That in a relatively caudal area resulted in a downward movement
      of the ipsilateral eye, accompanied by an upward movement of the contralateral
      eye. Intorsion of the contralateral eye was also evoked from a relatively dorsal
      area. These results indicate that Purkinje cells connected with different
      components of the vestibulo-ocular reflex arc have a differential localization
      within the flocculus.

PMID- 19605007
TI  - Differential localization of rabbit's flocculus Purkinje cells projecting to the
      medial and superior vestibular nuclei, investigated by means of the horseradish
      peroxidase retrograde axonal transport.
AB  - The retrograde axonal transport of horseradish peroxidase (HRP) was used to study
      distribution of those Purkinje cells in the flocculus which project to the medial
      and superior vestibular nuclei of albino rabbits. HRP was injected
      electrophoretically into those nuclei and after survival for 24-48 h the
      flocculus was examined microscopically. It was found that Purkinje cells
      projecting to the medial nucleus were located relatively rostrally, while those
      projecting to the superior nucleus lay relatively caudally. These two groups of
      Purkinje cells, however, were distributed in such a way as to yield an
      interdigitated striped pattern over the surface of the flocculus.

PMID- 19605008
TI  - Cat efferent vestibular system: weak suppression of primary afferent activity.
AB  - Efferent vestibular neurons identified electrophysiologically in the brain stem
      do not receive a short latency synaptic input from the ipsilateral labyrinth.
      Central electric stimulation of these neurons influenced the resting discharge of
      only 8% of the primary afferent vestibular neurons. Caloric or electric
      stimulation of the vestibular input was ineffective in changing the spontaneous
      activity of contralateral primary afferent vestibular neurons.

PMID- 19605009
TI  - On the role of brain noradrenaline and the pituitary-adrenal axis in avoidance
      learning. I. Studies with corticosterone.
AB  - A marked impairment of the acquisition of a one-way active avoidance response was
      observed in rats after a 6-hydroxydopamine-induced lesion of the ascending
      (dorsal) noradrenaline bundle to the cortex cerebri in combination with
      adrenalectomy. The deficit in acquisition was prevented by low daily doses of
      corticosterone. Neither adrenalectomy nor lesions of the dorsal noradrenaline
      bundle alone caused a deficit. It is suggested that brain noradrenaline neurons
      and the pituitary-adrenal axis may interact in the control of active avoidance
      behavior. Finally, noradrenaline neurons appear not to play any role in
      extinvtion of punished behavior.

PMID- 19605010
TI  - Organum vasculosum lamina terminalis: innervation by serotonin neurons of the
      midbrain raphe.
AB  - The monoamine innervation of the organum vasculosum lamina terminalis (OVLT) was
      studied using fluorescence histochemistry and the autoradiographic tracing
      method. Fluorescence histochemistry demonstrates serotonin terminals in close
      proximity to the capillary plexus of the OVLT, in the same region where the
      apparent terminals of luteinizing hormone-releasing hormone neurons are
      localized. No catecholamines are evident in this area. Autoradiographic studies
      indicate that the serotonin innervation of the OVLT arises in the midbrain raphe
      nuclei. Thus, the OVLT is similar to other circumventricular organs, the
      subfornical organ and the subcommissural organ, in receiving a rich innervation
      from serotonin neurons.

PMID- 19605011
TI  - Ultrastructure of human fetal sympathetic ganglia after permanganate fixation -
      absence of granular vesicles.
AB  - Midterm human fetal sympathetic ganglia were studied using the formaldehyde
      induced fluorescence technique for demonstrating catecholamines, and after
      glutaraldehyde-OsO(4) or permanganate fixation for electron microscopy. The
      fluorescence technique indicated the presence of catecholamines in most of the
      developing neurons. After glutaraldehyde-OsO(4) fixation large granular vesicles
      were found in the perikarya, but a more specific technique for catecholamines,
      permanganate fixation, revealed no granular vesicles at this stage of
      development. This indicates that most of the catecholamines are loosely bound in
      a non-granular store during development.

PMID- 19605012
TI  - Vestibular projections to the nucleus intercalatus of Staderini mapped by
      retrograde transport of horseradish peroxidase.
AB  - Medullary afferent projections to the nucleus intercalatus of Staderini have been
      studied by retrograde transport of horseradish peroxidase (HRP) from highly
      localized injections. This nucleus receives afferent projections particularly
      from the medial and descending vestibular nuclei as well as from the nucleus
      praepositus hypoglossi of both sides. The nucleus intercalatus of Staderini
      represents therefore an area of integration for the vestibular systems of both
      sides.

PMID- 19605013
TI  - Topographical distribution of estrogen-concentrating cells in the brain and
      pituitary of the squirrel monkey.
AB  - The specific anatomical pattern of cells that concentrate estradiol in the brain
      and pituitary of ovariectomized squirrel monkey was determined by
      radioautography. In the brain, a nuclear concentration of radioactivity was
      observed in neurons which are accumulated in specific areas including the
      preoptic area, the medio basal area of the hypothalamus (n. infundibularis, n.
      premammillaris) and the amygdala. In the anterior pituitary a large number of
      estrogen-binding cells were seen. No significant labeling was observed in the
      intermediate and posterior lobes.

PMID- 19605014
TI  - Responses in the rostral medulla to electrical stimulation of an intranasal
      trigeminal nerve: convergence of oral and nasal inputs.
AB  - Projections of trigeminal afferents from the intranasal ethmoid nerve were
      examined in the area of trigeminal nucleus oralis. Electrical stimulation of the
      ethmoid nerve yielded two clusters of responses. In ventral nucleus oralis and
      the adjacent reticular formation responses were recorded as might be expected
      from an ophthalmic projection. However, a more dorsal projection was also found
      in the midst of oral cavity responses (taste and tactile), including some neurons
      responding to afferents of both intranasal and oral cavity origin.

PMID- 19605015
TI  - The effect of denervation of Merkel cells in cats.
AB  - The morphology of Merkel cells in sinus hair follicles of the upper lip
      (vibrissae with a circular blood sinus), and in touch domes of the glabrous skin
      of the nose, was investigated in cats up to 12 weeks after resection of the
      infraorbital nerve. Even 12 weeks after denervation there was neither an
      ultrastructural alteration of Merkel cells nor a reduction of their number in
      sinus hair follicles. Also in touch domes the Merkel cells did not disappear.

PMID- 19605016
TI  - The effects of selective catecholamine depletions by 6-hydroxydopamine on ethanol
      preference in rats.
AB  - Two groups of ethanol-drinking rats were subjected to differential treatments
      with 6-hydroxydopamine in order to selectively destroy norepinephrine- and
      dopamine-containing neurons in the brain. Animals with extensive depletions of
      norepinephrine and dopamine produced by treatment with pargyline prior to 6
      hydroxydopamine infusions showed a significant attenuation of preference for
      alcohol. However, where norepinephrine neurons were protected from the neurotoxic
      effects of 6-hydroxydopamine by pretreatment with desmethylimipramine, the
      consequent effects on ethanol preference were not significant. It was suggested
      that catecholamines are involved in the mediation of ethanol self-administration
      with norepinephrine possibly playing the dominant role.

PMID- 19605017
TI  - The involvement of catecholaminergic mechanisms in the behavioural action of
      vasopressin.
AB  - The effect of lysine-8-vasopressin (300 mU/kg b.w.) has been tested in a single
      trial step-down passive avoidance test. Vasopressin treatment resulted in an
      improvement of step-down latency in normal rats, but this action disappeared when
      the animals were pretreated with 80 mg/kg alpha-methyl-p-tyrosine (alpha-MT).
      Vasopressin treatment decreased the hypothalamic, septal and striatal dopamine
      (DA) levels. Following vasopressin, the turnover of norepinephrine (NE) increased
      in the hypothalamus, as did these of DA in the septum and striatum. The data
      suggest that the cerebral catecholaminergic system might be one of the important
      mediators of the behavioural action of vasopressin.

PMID- 19605018
TI  - Muscarinic cholinergic receptor binding in bovine retina.
AB  - Using [(3)H] quinuclidinyl benzylate ([(3)H] QNB) muscarinic cholinergic
      receptors have been demonstrated in crude membrane fractions of bovine retina.
      Specific [(3)H] QNB binding is saturable with a K(D) of 0.5 nM and a maximal
      number of muscarinic agonists and antagonists for displacing specific [(3)H] QNB
      binding closely parallel the affinities for muscarinic receptors in rat brain and
      guinea pig ileum. The findings may explain atropine sensitive effects of
      muscarinic agonists on the electroretinogram and on retinal cells in vitro.

PMID- 19605019
TI  - The effect of ouabain on the bioelectrical activity of extrapyramidal cortex and
      caudate nucleus in the rabbit brain.
AB  - Bioelectrical activity of chronically implanted rabbits was studied after
      different doses of ouabain (0.25-1.5 microg) administered topically on the
      extrapyramidal cortex. The results indicate that the EEG effect of ouabain (relax
      pattern, epileptiform activity or spreading depression) depends on the dose
      employed. It is interesting that epileptiform activity appeared in the
      ipsilateral caudate nucleus during phenomena similar to the 'spreading
      depression' in the ipsilateral extrapyramidal cortex, i.e. in the site of ouabain
      administration.

PMID- 19605020
TI  - Dual organization of motor corticospinal tract in the cat.

PMID- 19605022
TI  - The in vivo synthesis of stable RNA within the vagus nerve following vagotomy.

PMID- 19605021
TI  - Delta sleep-inducing peptide (DSIP): EEG and motor activity in rabbits following
      intravenous administration.

PMID- 19605023
TI  - A simple apparatus for the injection of small (nanolitre) volumes of horseradish
      peroxidase.

PMID- 19605024
TI  - Rapid degradation of substance P and related peptides during microiontophoretic
      experiments.

PMID- 19605025
TI  - Average muscle tension triggered by stimulation of gamma fusimotor fibers.

PMID- 19605026
TI  - Lipophilic nerve sprouting factor(s) isolated from denervated muscle.

PMID- 19605027
TI  - The reaction time of eye-head coordination in man.

PMID- 19605028
TI  - Fusion between smooth cisternae and the plasmalemma of the growth cone: a
      morphogenetic mechanism of the growing nerve fiber.

PMID- 19605029
TI  - Differential termination of large-diameter and small-diameter primary afferent
      fibers in the spinal dorsal gray matter as indicated by labeling with horseradish
      peroxidase.

PMID- 19605030
TI  - Localization of aspartate aminotransferase and glutamic dehydrogenase in the
      Edinger-Westphal and oculomotor nuclei of Lacerta lepida.

PMID- 19605031
TI  - Evidence for selective susceptibility of hippocampus to spreading depression
      induced by vasopressin.

PMID- 19605032
TI  - Presynaptic effect of L-glutamic acid on the release of dopamine in rat striatal
      slices.

PMID- 19605033
TI  - Action of GABA on neurones and satellite glial cells of cultured rat dorsal root
      ganglia.

PMID- 19605034
TI  - A cholinergic connection between normal aging and senile dementia in the human
      hippocampus.

PMID- 19605036
TI  - Increased release of [(3)H]dopamine during low O(2) stimulation of rabbit carotid
      body in vitro.

PMID- 19605035
TI  - Modification by adrenergic blocking agents of arginine vasotocin-induced
      prolactin secretion in vitro.

PMID- 19605037
TI  - A new fixed-array multi-microelectrode system designed for long-term monitoring
      of extracellular single unit neuronal activity in vitro.

PMID- 19605038
TI  - Mapping of collateral projections with the HRP-method.

PMID- 19605039
TI  - An integration centre of the mormyrid fish brain: the auricula cerebelli. An HRP
      study.

PMID- 19605040
TI  - Descending input from the pneumotaxic system to the lateral respiratory nucleus
      of the medulla. An anatomical study with the horseradish peroxidase technique.

PMID- 19605041
TI  - Retrograde anoxal transport of fluorescent substances in the rat's forebrain.

PMID- 19605042
TI  - Uptake and retrograde transport of HRP by axons of intact and damaged peripheral
      nerve trunks.

PMID- 19605043
TI  - Auditory-visual interaction in cat orbital-insular cortex.

PMID- 19605044
TI  - Mouse somatosensory cortex: development of the alterations in the barrel field
      which are caused by injury to the vibrissal follicles.

PMID- 19605045
TI  - A small guillotine to prepare brains for sectioning in defined, odd planes.

PMID- 19605046
TI  - The sympathetic efferent discharges during the Bezold-Jarisch reflex.

PMID- 19605047
TI  - Synapses between identified neuronal elements. An electron microscopic
      demonstration of degenerating axon terminals synapsing with Golgi impregnated
      neurons.

PMID- 19605048
TI  - The influence of pentobarbitone on the distribution of membrane in cortical
      synapses.

PMID- 19605049
TI  - Evidence for a neurotoxic effect of ascorbic acid after an intranigral injection
      in the cat.

PMID- 19605050
TI  - Binding of barium to neurosecretory granules in the snail brain: a possible
      molecular mechanism of neuro-hormone release.

PMID- 19605052
TI  - Reward-aversion analysis of rat mesencephalon.

PMID- 19605051
TI  - The influence of intracaudate injection of apomorphine on metabolism of serotonin
      in hippocampus and mesencephalon of the rabbit.

PMID- 19605053
TI  - GABA induced membrane current noise and the time course of the inhibitory
      synaptic current in crayfish muscle.

PMID- 19605054
TI  - On the development of the gigantocerebellum in the mormyrid fish Pollimyrus
      (Marcusenius) Isidori.

PMID- 19605055
TI  - Evidence that some intrinsic neurons of the intestine contain somatostatin.

PMID- 19605056
TI  - Cat reticular neurons projecting to the region of the medial vestibular nucleus.

PMID- 19605057
TI  - Cerebellar corticonuclear fibers: evidence of zones in the primate anterior lobe.

PMID- 19605058
TI  - The cortical source of the alpha rhythm.

PMID- 19605059
TI  - Some ipsilateral projections to areas PF and PG of the inferior parietal lobule
      in monkeys.

PMID- 19605060
TI  - Mutant spastic Han-Wistar rats: biochemical abnormalities in their striata.

PMID- 19605061
TI  - Morphine enhances amygdaloid seizures and increases inter-ictal spike frequency
      in kindled rats.

PMID- 19605062
TI  - Reinstatement of morphine drinking in hypophysectomized rats following injections
      of ACTH.

PMID- 19605063
TI  - REM sleep rebound during withdrawal from chronic amphetamine administration is
      blocked by chloramphenicol.

PMID- 19605065
TI  - Passive avoidance learning improved with intermittent but not continuous trains
      of post-trial rewarding hypothalamic stimulation.

PMID- 19605066
TI  - Specific cytoplasmic inclusions of frog ependymoglial cells.

PMID- 19605064
TI  - Enhancement of paradoxical sleep by short light periods in the golden hamster.

PMID- 19605067
TI  - Autoradiographic localization of [(3)H]reserpine in rat brain: correlation with
      distribution of monoaminergic neurones.

PMID- 19605068
TI  - Trigemino-cerebellar projections in normal and reeler mutant mice.

PMID- 19605069
TI  - Intracranial self-stimulation in cats under local anesthesia of the cervical vago
      sympathetic trunk.

PMID- 19605070
TI  - Immunohistochemical evidence for an ACTH-like substance in hypothalamic LH-RH
      neurons.

PMID- 19605071
TI  - Unmyelinated axon networks in root portions of human primary canines.

PMID- 19605072
TI  - Preoptic multiunit activity correlates of the photosexual reflex in quail.

PMID- 19605073
TI  - Selective blockade of excitatory caudate responses to nigral stimulation by
      microiontophoretic application of dopamine antagonists.

PMID- 19605074
TI  - Cyclic adenosine 3',5'-monophosphate in epileptogenic foci induced by penicillin.

PMID- 19605075
TI  - Precocious sleep modifications in the evolution of experimental Kuru in rhesus
      monkeys.

PMID- 19605077
TI  - Effect of suprachiasmatic ablation on the daily temperature rhythm.

PMID- 19605078
TI  - Induction of mounting behaviour in female and male rats by lisuride.

PMID- 19605076
TI  - On the mechanism of action of the antidepressant drugs amitriptyline and
      nortriptyline. Evidence for 5-hydroxytryptamine receptor blocking activity.

PMID- 19605079
TI  - L-proline inhibition of long-term memory formation.

PMID- 19605080
TI  - Participation of the dilute locus in the genetic control of self-stimulation
      behaviour in the mouse.

PMID- 19605081
TI  - A radioimmunoassay for thyroliberin (TRH). comparison with a TRH radioreceptor
      assay.
AB  - A radioimmunoassay (RIA) for thyroliberin (TRH) is described which differs on
      several points from the previously published ones. A TRH antiserum was raised in
      rabbits against TRH coupled to a seed-globulin from the sun-flower; [(3)H]TRH was
      used as radioligand and precipitation of the antibody-antigen complex was
      achieved with polyethylene glycol (PEG). The RIA sensitivity is around 4 pg. It
      is compared to a radioreceptor assay (RRA) which has been previously settled [5]
      using a pituitary cell line in culture (GH3 clone) (sensitivity: 200 pg). No
      cross-reactivity is seen in either assay with various hormones or TRH analogues,
      except with some methylated derivatives. Both techniques led to comparable values
      when biological extracts were assayed, provided they were partially purified.

PMID- 19605082
TI  - Antidromic activation of pyramidal tract neurons following topical penicillin
      application. A possible mechanism in the generation of paroxysmal events.
AB  - Pyramidal tract (PT) neurons identified through antidromic stimulation were
      recorded with extracellular multibarrelled microelectrodes in the rat motor
      cortex. Topical application of small amounts of penicillin to the PT fibers at
      the medullary level induced the generation of action potentials (APs) near the
      injection site. These APs, which propagated antidromically to the cortex, could
      be characterized by collision test. It is suggested that a similar phenomenon may
      occur on intracortical collaterals of PT fibers within a cortical penicillin
      focus. Such 'ectopic' AP generation may contribute significantly to the
      generation of paroxysmal events.

PMID- 19605083
TI  - Does the skin tell the somatosensory cortex how to construct a map of the
      periphery?
AB  - When the muzzle of a mouse bears an occasional extra whisker, the corresponding
      barrelfield (in the contralateral somatosensory cortex) contains an extra barrel
      in a topologically equivalent place and vice versa. Since the pattern of
      vibrissal follicles is laid down 7 days before birth and that of the barrels 3
      days after birth, the former pattern appears to be responsible for the
      establishment of the latter. We propose that the answer to the title's question
      is yes.

PMID- 19605084
TI  - Thromboxane A(2) as a possible natural ligand for benzodiazepine receptors.
AB  - Receptors for benzodiazepines have recently been found in the brain but the
      natural ligand which can occupy these receptors is unknown. In a rat vascular
      preparation diazepam and chloridiazepoxide were found to inhibit pressor
      responses to noradrenaline and angiotensin but not those to potassium and
      vasopressin with IC(50) concentrations similar to those reported for displacement
      of [(3)H]diazepam from brain receptors. Imidazole, an inhibitor of thromboxane
      A(2) synthesis had similar actions to the benzodiazepines. Interactions between
      imidazole and the benzodiazepines suggested that the latter may be competitive
      antagonists of thromboxane A(2). The possibility that thromboxane A(2) may be the
      natural ligand is supported by recent evidence that brain tissue contains high
      levels of this substance.

PMID- 19605085
TI  - Motor reactions to perturbations of gait: proprioceptive and somesthetic
      involvement.
AB  - If an obstacle impedes the forward swing of a cat's foot during stepping, the
      animal responds by rapidly lifting the foot over the obstacle. Electrical
      activity of hindlimb muscles was recorded during such reactions in conscious
      cats. After anaesthesia of the dorsum of the foot, some muscles no longer took
      part in the reactions and simple stretch responses were observed in the ankle
      flexors, which had previously shown a more complex pattern of activation. This
      result emphasizes the importance of cutaneous afferents in contributing to the
      control of motor responses to unexpected perturbations.

PMID- 19605086
TI  - Sacral spinal innervations of the rectal and vesical smooth muscles and the
      sphincteric striated muscles as demonstrated by the horseradish peroxidase
      method.
AB  - To investigate the central organization of efferent neurons innervating the
      rectal and vesical smooth muscles and the sphincteric striated muscles in the
      cat, horseradish peroxidase (HRP) was injected into each of these structures and
      retrogradely labeled neurons were identified in the sacral spinal cord. Following
      HRP injections into these smooth muscle structures, labeled neurons were found in
      the intermediolateral and intermediolateral cell columns, the cell group X of
      Onuf and the nucleus myoleioticus medialis of the sacral cord. HRP injections
      into the external anal sphincter and bulbospongiosus muscles showed labeled
      neurons in the cell group X of Onuf and some in the nucleus myoleioticus
      medialis.

PMID- 19605087
TI  - Local degradation of luteinizing hormone-releasing hormone (LH-RH) in the rat
      central nervous system.
AB  - Peptidases inactivating luteinizing hormone-releasing hormone (LH-RH) were found
      to be present in two subcellular fractions prepared from the following areas of
      the central nervous system of male and female rats: thalamus, hypothalamus,
      cortex and cerebellum. LH-RH immunoreactivity was also detected in these
      fractions after peptidase activity had been removed by heat denaturation. These
      findings support the concept that LH-RH may have a role in modulating neuronal
      activity within the central nervous system (CNS).

PMID- 19605088
TI  - On the function of the fast long spinal inhibitory pathway from forelimb
      afferents to flexor digitorum longus motoneurones in cats and dogs.
AB  - In high spinal cats an oligosynaptic inhibitory reflex pathway from forelimb
      afferents specifically to hindlimb flexor digitorum and hallucis longus (FDL)
      motoneurones has been established. The present investigation yielded further
      results for a functional interpretation of this specific pathway. The IPSPs in
      FDL motoneurones could be evoked by weak innocuous mechanical stimuli to the
      forepaw. During fictive locomotion they were predominantly transmitted during the
      active phase of the FDL i.e., during the extension phase. With monosynaptic
      reflex testing a similar propriospinal inhibition of FDL motoneurones was
      demonstrated in dogs. It is assumed, that this propriospinal inhibition of FDL
      motoneurones implies a mechanism for preventing a plantar flexion of the toes
      during periods of the hindlimb extension phase.

PMID- 19605089
TI  - Efferent connections of the septal area in a lizard (tupinambis nigropunctatus).
AB  - Electrolytic lesions were placed in the septal area of the lizard Tupinambis
      nigropunctatus, and the subsequent anterograde degeneration was studied by the
      use of reduced silver techniques. Telencephalic projections were found to the
      dorsal cortex and the nucleus of the anterior commissure. Descending fibers
      appeared to terminate in the preoptic area, dorsolateral and dorsomedial thalamic
      nuclei, medial thalamic nucleus, nucleus periventricularis hypothalami, lateral
      hypothalamic area, mamillary body and mesencephalic central grey. All of these
      connections were found to be ipsilateral.

PMID- 19605090
TI  - Aberrant ipsilateral retinotectal projection following optic nerve section in
      Xenopus.
AB  - Optic fibre regeneration in young Xenopus was studied by [(3)H]proline
      autoradiography and by mapping the visuotectal projection electrophysiologically
      from 5 to 210 days after sectioning the right optic nerve. Regenerated optic
      fibers were demonstrated morphologically both in the contra and ipsilateral
      tecta. In contrast, electrophysiological studies showed that the visuotectal
      projection was detectable only in the contralateral tectum. The apparent
      disparity between morphological and electrophysiological results is discussed.

PMID- 19605091
TI  - The effect of exposure to continuous light on the ERG of syrian hamsters.
AB  - Reduction of ERG wave amplitude was found after exposure to continuous light in
      albino and pigmented hamsters. The reduction was strongest in albino hamsters. No
      effect on wave threshold was seen. Changes in time-to-peak were only found for
      the b-wave in exposed albino hamsters. Comparing these results with those
      previously found in rats under identical experimental conditions, we noted in
      hamsters: smaller reduction of amplitude, no increase of threshold and no
      increase of a-wave time-to-peak.

PMID- 19605092
TI  - Depression of lingual tactile sensation during chemical stimulation of the human
      tongue.
AB  - The subjectively estimated magnitude of human tactile sensation elicited by
      tapping the tongue was depressed during taste stimulation by 3 and 6% NaCl
      solution, 0.1% quinine and 0.5% acetic acid. No significant change in the tactile
      sensation occurred during flow of 2-20% sucrose solution. The result may be
      attributed to presynaptic inhibition exerted by gustatory onto lingual tactile
      afferents.

PMID- 19605093
TI  - The activity of some neurotransmitter-synthetizing enzymes in experimental cobalt
      epilepsy.
AB  - The activities of tyrosine hydroxylase (TH), dihydropteridine reductase (DHPR),
      aromatic aminoacid decarboxylase (AAD) and glutamic acid decarboxylase (GAD),
      enzymes involved in the synthesis of neurotransmitters possibly implicated in
      epilepsy, were measured in some brain areas of rats with cobalt-induced epilepsy.
      Although TH, AAD and GAD were significantly decreased in the cortex of treated
      animals, the reduction was not correlated with the development of the
      electroclinical patterns of epilepsy. The reduction observed might be better
      explained by nerve degeneration caused by the experimental lesion.

PMID- 19605094
TI  - Properties of amacrine cell responses recorded from isolated fish retinae.

PMID- 19605095
TI  - The activity of cells of nucleus reticularis tegmenti pontis during spontaneous
      locomotion in the decorticate cat.

PMID- 19605096
TI  - Effect of temperature on the initial formation of neurites of mouse neuroblastoma
      cells.

PMID- 19605097
TI  - Neuronal abnormalities associated with impaired myelination during brain
      development: a golgi study of neocortex in the Jimpy mouse.

PMID- 19605098
TI  - Regional distribution of catecholamines in monkey cerebral cortex, evidence for a
      dopaminergic innervation of the primate prefrontal cortex.

PMID- 19605099
TI  - Thalamocortical projections to the temporal and parietal association cortices in
      the rat.

PMID- 19605100
TI  - The substance P projections to the frontal cortex and the substantia nigra.

PMID- 19605102
TI  - Inhibitory action of iontophoretically applied methionine-enkephalin and leucine
      enkephalin on tuberal hypothalamic neurons.

PMID- 19605101
TI  - Substance P projections to the entopeduncular nucleus, the medial preoptic area
      and the lateral septum.

PMID- 19605103
TI  - 6-Hydroxydopamine lesions of rat locus coeruleus alter brain glucose consumption,
      as measured by the 2-deoxy-D-[(14)C]glucose tracer technique.

PMID- 19605104
TI  - Effects of capsaicin on hypothalamic thermo-sensitive neurons in the rat.

PMID- 19605105
TI  - Substantia nigra dopamine neurons: separate populations project to neostriatum
      and allocortex.

PMID- 19605106
TI  - Dependency of the resting membrane potential on the extracellular chloride
      concentration in identified neurons of Helix pomatia.

PMID- 19605107
TI  - Collateral connections to the lateral reticular nucleus from cervical
      propriospinal neurones projecting to forelimb motoneurones in the cat.

PMID- 19605108
TI  - Autoradiographic localization of the uptake of [(3)H]- GABA and [(3)H]L-glutamic
      acid in neurones and glial cells of cultured dorsal root ganglia.

PMID- 19605109
TI  - Characteristics of corticothalamic neurons in area 17 of the cat.

PMID- 19605110
TI  - Connections of the mediodorsal nucleus of the thalamus in the tree shrew. I.
      Afferent connections.

PMID- 19605111
TI  - The pattern of myelination along the developing rat optic nerve.

PMID- 19605112
TI  - Localization of rabbit's flocculus Purkinje cells projecting to the cerebellar
      lateral nucleus and the nucleus prepositus hypoglossi investigated by means of
      the horseradish peroxidase retrograde axonal transport.

PMID- 19605113
TI  - Activity of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in cerebrospinal fluid
      of patients with demyelinating disorders.

PMID- 19605115
TI  - Lack of correlation between taurine levels in 16 brain regions and paroxysmal
      discharges in the thalamocortical circuit.

PMID- 19605114
TI  - Visual direction depends on the operation of spatial constancy mechanisms: the
      oculobrachial illusion.

PMID- 19605117
TI  - Stearyl-alcohol biosynthesis from stearyl-CoA in mouse brain microsomes in normal
      and dysmyelinating mutants (quaking and jimpy).

PMID- 19605116
TI  - Growth of vascular sympathetic axons into the hippocampus after lesions of the
      septo-hippocampal pathway: a pitfall in brain lesion studies.

PMID- 19605118
TI  - Fetal Tay-Sachs disease brain cells in culture: lack of turnover in
      [(14)C]glucosamine-labeled G(M2).

PMID- 19605119
TI  - Strain differences in aggressive behaviour of female mice against lactating and
      non-lactating individuals.

PMID- 19605120
TI  - Relationship between paradoxical sleep and time-dependent improvement of
      performance in BALB/c mice.

PMID- 19605121
TI  - Experimental study of intracranial pressure during rapid eye movement sleep in
      the chronic cat.

PMID- 19605122
TI  - Changes in structure and electrophysiological function of retinal neurones
      induced by laser irradiation.

PMID- 19605124
TI  - Chopper units recorded in the cochlear nucleus of the awake cat.

PMID- 19605123
TI  - Uptake of cations by neuronal surface and metallic intoxications.

PMID- 19605125
TI  - Diet deprived in essential fatty acids affects brain myelination.

PMID- 19605126
TI  - Deviations from simple binomial predictions of transmitter release at frog
      neuromuscular junctions.

PMID- 19605128
TI  - Differential inhibitory effects of volleys from dorsal raphe nucleus upon spinal
      and spino-bulbo-spinal reflexes.

PMID- 19605127
TI  - Plasticity of cerebellar efferents after neonatal lesions in albino rats.

PMID- 19605129
TI  - Opiate receptors on mesolimbic dopaminergic neurons.

PMID- 19605130
TI  - Localization of neurons giving rise to the oculomotor parasympathetic outflow: a
      HRP study in cat.

PMID- 19605131
TI  - A modified epon embedding and counterstaining procedure for light microscopic
      examination of Golgi impregnated neurons in vertebrates.

PMID- 19605132
TI  - Immunocytochemical localization of alpha-melanocyte stimulating hormone (alpha
      MSH)-like compounds in the rat nervous system.

PMID- 19605133
TI  - Axonal transport of glutamic acid decarboxylase in crayfish peripheral nerve:
      dependence on contact between soma and axon.

PMID- 19605134
TI  - Annual rhythm of serum melatonin in man.

PMID- 19605135
TI  - 5-Hydroxytryptamine and avoidance performance in the rat. Antagonism of the acute
      effect of p-chloroamphetamine by zimelidine, an inhibitor of 5-hydroxytryptamine
      uptake.

PMID- 19605136
TI  - GABA agonists and audiogenic seizures.

PMID- 19605137
TI  - Differential effects of neonatal 6-hydroxydopamine treatment on the catecholamine
      content of hypothalamic nuclei and brain stem regions.

PMID- 19605138
TI  - Differential effects of a high-carbohydrate diet on the behavior of male and
      female rats.

PMID- 19605139
TI  - Topographical representation of masticatory muscles in the motor trigeminal
      nucleus in the rabbit: A HRP study.
AB  - Myotopical localization of masticatory motoneurons was studied in rabbit by means
      of the horseradish peroxidase (HRP) method. As described by Meessen and Olszewsky
      [6], the motor trigeminal nucleus of rabbit is divided into 3 divisions;
      caudoventromedially alpha, rostroventromedially beta and dorsolaterally gamma
      nuclei. Within the alpha nucleus, the anterior digastric motoneurons are located
      ventromedially and the mylohyoid motoneurons dorsolaterally. Lateral pterygoid
      motoneurons are situated in the beta nucleus. Within the gamma nucleus, the
      temporal, masseter and medial pterygoid muscles are represented medially,
      centrally and ventrolaterally, respectively.

PMID- 19605140
TI  - Topographical representation of peripheral branches of the facial nerve within
      the facial nucleus: A HRP study in the cat.
AB  - Representation of peripheral branches of the facial nerve within the facial
      nucleus of the cat was examined by utilizing retrograde axonal transport of
      horseradish peroxidase (HRP), which was injected into groups of muscles supplied
      by each of the main peripheral branches of the facial nerve. The cervical branch
      was represented in the ventromedial division of the facial nucleus, the posterior
      auricular branch in the medial division, the temporal branch in the intermediate
      division, the zygomatico-orbital branch in the dorsal division, the superior
      labial branch in the lateral division and the inferior labial branch in the
      ventrolateral division.

PMID- 19605141
TI  - Descending projection of the nucleus tegmentalis latero-dorsalis to the spinal
      cord; studied by the horseradish peroxidase method following 6-hydroxy-DOPA
      administration.
AB  - Descending projection of the nucleus tegmentalis laterodorsalis (TLD) to the
      spinal cord was investigated using the horseradish peroxidase (HRP) method
      following the systemic administration of 6-hydroxy-DOPA (6-OH-DOPA). 6-OH-DOPA
      pretreatment resulted in an intense labeling of the cell group at the
      laterocaudal portion of TLD after the injection of HRP to the lower segments of
      the spinal cord. Whereas in untreated rats, cells at the laterocaudal portion of
      TLD were faintly labeled. Such indirect effect correlated with a reduction in the
      number of fluorescent catecholamine nerve terminals in the spinal cord after 6-OH
      DOPA injection, suggesting that the descending projection from laterocaudal
      portion of TLD to the spinal cord might be influenced by the catecholamine
      neurons in the central nervous system.

PMID- 19605142
TI  - Relations between cell body size, axon diameter and axon conduction velocity of
      cat sciatic alpha-motoneurons stained with horseradish peroxidase.
AB  - The relations between cell body size, intramedullary axon diameter and axon
      conduction velocity were examined in cat sciatic alpha-motoneurons after
      intracellular staining with horseradish peroxidase. All relations showed
      significant (P < 0.001) positive linear correlation coefficients.

PMID- 19605143
TI  - Daily variations of cerebral tyrosine in two inbred strains of mice and their
      F(1) hybrids.
AB  - The diurnal rhythms of endogenous cerebral tyrosine in 15 week-old mice from
      BALB/C/Orl and C57 BL/6/Orl strains and their reciprocal F(1) hybrids, placed on
      a fixed 12/12 h dark-light schedule, were determined over a 24 h period in the
      fore-brain and hind-brain. Significant inter-strain differences in mean tyrosine
      levels were described in both structures. The main finding was that BALB/C
      exhibited a significant 24 h rhythm whereas a 12 h rhythm was found in C57/BL. In
      F(1) hybrids, daily tyrosine rhythm appeared in both structures as a combination
      of the 2 parental ones. These findings support the suggestion that genetic
      factors may affect biological rhythms.

PMID- 19605144
TI  - Localization of the micturition reflex center at dorsolateral pontine tegmentum
      of the rat.
AB  - Various electrolytic lesions have been made to elucidate the 'micturition reflex
      center' at the rat dorsolateral pontine tegmentum. The bilateral lesion occupying
      the caudal part of nucleus tegmentalis laterodorsalis (TLD)( *) caused the
      urinary disorders. However, they could not be observed after the bilateral
      destruction of locus coeruleus.

PMID- 19605145
TI  - Diverging influences on Renshaw cell responses and monosynaptic reflexes from
      stimulation of capsula interna.
AB  - In anaesthetized cats responses of lumbar Renshaw cells to anti- and orthodromic
      spinal root and muscle nerve shocks were recorded with and without conditioning
      stimulation of the contralateral capsula interna. Responses to antidromic test
      stimuli were decreased by supraspinal conditioning in 48 of 65 cases over their
      whole course and over a range up to 60 ms after the conditioning stimulation. The
      corresponding monosynaptic reflexes, however, were facilitated up to 250% under
      these conditions. Reduction of orthodromic responses was apparent in 12 of 44
      cases, but might have been masked in others due to concomitant motoneurone
      facilitation. These results indicate divergent descending influences on
      motoneurones and related Renshaw cells, mediated via the capsula interna.

PMID- 19605146
TI  - Effect of cocultivation of brain tissues on leucine and glycerol-3-phosphate
      incorporation.
AB  - Studies on the interaction between cortex grey matter (CC), diencephalon (DE),
      mesencephalon (ME) and pure glial cells free of neurons were undertaken in
      explant cultures. The culture system provided the formation of neuritic bridges
      between individual tissue pieces. Cocultivation of different brain tissues
      resulted in changes of leucine and glycerol-3-phosphate incorporation
      characteristic for individual brain areas. Glial cell (GC) did not respond to
      innervation by neurites of various sources. Glycerol-3-phosphate uptake rates
      were substantially altered in cocultures containing neurons and glia.

PMID- 19605147
TI  - Responses of raphespinal and other bulbar raphe neurones to stimulation of the
      periaqueductal gray in the cat.
AB  - The relationship between the periaqueductal gray (PAG) and nucleus raphe magnus
      (NRM) has been investigated. Electrical stimulation of the PAG in decerebrate or
      chloralose anaesthetised cats resulted in synaptic activation of raphespinal and
      other cells in NRM. These results support the view that analgesia of the limbs,
      trunk and tail produced by stimulation of the PAG in conscious animals may be
      mediated by synaptic activation of raphespinal neurones.

PMID- 19605148
TI  - A synthetic, conformationally restricted analogue of L-glutamic acid which acts
      as a powerful neuronal excitant.
AB  - The activity of a synthetic compound, cis-1-aminocyclopentane-1,3-dicarboxylic
      acid, which possesses a conformationally very restricted molecule, has been
      compared with that of L-glutamic acid and a number of other compounds as a
      neuronal excitant. The new compound is about 10-fold more active than glutamate
      and its rigidity indicates that it reacts only with glutamate receptors and not
      with those responsive to aspartate.

PMID- 19605149
TI  - 5-Hydroxytryptamine neurons and the sleep-wakefulness cycle. Effects of
      methergoline and zimelidine.
AB  - Methergoline, a 5-hydroxytryptamine (5-HT) receptor blocking agent, produced a
      significant decrease in the number of slow wave sleep 2 (SWS 2) and paradoxical
      sleep (PS) episodes and an increase in the length of wakefulness (W) episodes.
      Zimelidine, a specific 5-HT uptake blocking agent, produced a significant
      reduction of the number of PS episodes and an increase in the number of spisodes
      spent in W and slow wave sleep 1 (SWS 1), the total time spent in SWS 1 being
      increased. The findings demonstrate that increases and decreases of 5-HT receptor
      activity will produce differential effects on SWS 2 events and on W mechanisms.

PMID- 19605150
TI  - Maintained discharge of rat suprachiasmatic neurons at different adaptation
      levels.
AB  - In the rat the response of suprachiasmatic nucleus neurons to steady retinal
      illumination at different adaptation luminances was studied. The results confirm
      that in this nucleus the discharge rate is more commonly increased than
      suppressed by light. Interval histograms indicate that a complex process
      underlies the discharge at any adaptation level. The suppressive or excitatory
      effect of light has a high threshold. Phasic stimuli appear to be relatively
      ineffective. These findings are consistent with the retino-suprachiasmatic
      function in circadian rhythm synchronization. An attempt was made to separate the
      effects of lateral geniculate from direct retinal inputs to the hypothalamus.

PMID- 19605151
TI  - Regional distribution of high-affinity L-tryptophan uptake in rat brain.
AB  - L-tryptophan is accumulated by slices of seven regions of the rat brain in a
      saturable, energy-depending fashion, with K(m)-values ranging from 53 to 142 muM.
      The maximal number of L-tryptophan accumulating sites differs only by about two
      fold for the brain regions investigated. The regional distribution of the high
      affinity L-tryptophan uptake does not correlate with the amount of serotonin
      synaptosomal uptake and apparent receptor binding. It is assumed that a specific
      role of the L-tryptophan uptake system within the serotoninergic system in the
      brain is questionable.

PMID- 19605152
TI  - Biochemical effects of nerve growth factor and its antibody on the vas defferens
      and the adrenal medulla.
AB  - The administration of nerve growth factor (NGF) to newborn and 30-day-old rats
      elicits a selective increase in tyrosine hydroxylase (TH) and dopamine B
      hydroxylase (DBH) activities both in the vas deferens and the adrenal medulla. In
      contrast, the administration of monospecific anti NGF-antibodies leads to no
      significant changes in TH and DBH activities in the vas deferens and the adrenal
      medulla. This discrepancy might indicate that NSF is not an absolute prerequisite
      for the development and maintenance of function of these organs, although they do
      not respond by a selective increase in TH and DBH activities.

PMID- 19605153
TI  - Distribution pattern of alkanes in whole brain mitochondria, microsomes,
      synaptosomes and myelin isolated from normal mouse.
AB  - An homologous series of n-alkanes, which are the major aliphatic hydrocarbons,
      has been identified in normal mouse brain and in brain subfractions: myelin,
      mitochondria, microsomes, synaptosomes. The distribution patterns are
      qualitatively similar within all the studied fractions and show approximately
      equal amounts of odd and even chains. These alkanes, present in minor amounts in
      all the brain subfractions, accumulate in the myelin.

PMID- 19605154
TI  - Enhancement of drug-induced motor activity by an inhibitor of phenylethanolamine
      N-methyltransferase.
AB  - The behavioral effects of DCMB (2,3-dichloro-alpha-methylbenzylamine, Lilly), an
      inhibitor of brain phenylethanolamine-N-methyltransferase (PNMT; EC 2.1.1.28),
      were studied in rats and mice. The drug decreased spontaneous motor activity and
      induced stereotypic gnawing in both species. The motor activity response of rats
      to d-amphetamine was enhanced after DCMB, and unusual stereotypic head bobbing
      developed. The stereotypic motor responses of mice to morphine were increased
      after DCMB. These findings suggest that adrenaline neurons (which project to the
      extrapyramidal system) are involved in normal motor activity and in the
      suppression of some forms of stereotypy.

PMID- 19605155
TI  - Running fits induced by direct administration of semicarbazide into the superior
      colliculus of the mouse.
AB  - Semicarbazide (SC), an antivitamin B(6), was injected directly into the superior
      colliculus of the mouse. A running fit preceded by excessive alertness, was
      induced by a very small dose of SC after a remarkably short latency as compared
      with systemic administration of SC. Afterwards, animals often exhibited
      repeatedly tonic and/or clonic convulsions and some died subsequently. Either
      intracollicular (i.c.) injection of pyridoxine at the same site, or
      intraperitoneal (i.p.) injection of aminooxyacetic acid, suppressed these
      manifestations. The behavioral changes after intracollicular injection of SC and
      the effect of the antidotes were similar to those by systemic administration of
      SC. The relationship between this induction of running fits and the gamma
      aminobutyrate-mediated system is discussed.

PMID- 19605156
TI  - Contralateral nucleocortical cells of the paraflocculus of tree shrew (Tupaia
      glis).

PMID- 19605157
TI  - Cortical afferents of the amygdaloid complex in the rat: an HRP study.

PMID- 19605158
TI  - Subcortical afferents of the amygdaloid complex in the rat: an HRP study.

PMID- 19605159
TI  - Cortical spreading depression and state-dependent learning. A negative finding.

PMID- 19605160
TI  - [(3)H]haloperidol and [(3)H]spiroperidol receptor binding after striatal
      injection of kainic acid.

PMID- 19605161
TI  - Evidence for a bilateral 'glomerular' projection from the red nucleus to the
      spinal nucleus of the trigeminal nerve in the cat.

PMID- 19605162
TI  - Two types of degenerating axon terminals in the basilar pontine nuclei of the
      opossum following cerebral cortical lesions.

PMID- 19605164
TI  - On the presynaptic nature of the quantal subunit.

PMID- 19605163
TI  - Dentate cooling in monkeys performing a visuo-motor pointing task.

PMID- 19605165
TI  - The action of dopamine on rat caudate neurones intracellularly recorded.

PMID- 19605166
TI  - Intra-amygdaloid applications of naloxone elicits severe withdrawal signs in
      morphine dependent rats.

PMID- 19605167
TI  - Restoration of activity for induction of experimental allergic peripheral
      neuritis by a combination of myelin basic protein P2 and gangliosides from
      peripheral nerve.

PMID- 19605168
TI  - Thyrotropin-Releasing Hormone tartrate (TRH-T) shortens concussion effects
      following head impact in mice.

PMID- 19605169
TI  - Extracts of uterine tissue stimulate endorphin release from anterior pituitary in
      vitro.

PMID- 19605170
TI  - A simple histochemical method for double labelling of neurons by retrograde
      axonal transport.

PMID- 19605171
TI  - Fluorocarbon FC 75: a new bathing medium for in vivo recordings in
      neurophysiology.

PMID- 19605172
TI  - Electroacupuncture: current strength-duration relationship for initiation of
      hypesthesia in man.

PMID- 19605173
TI  - Phasic control of the transmission in the excitatory and inhibitory reflex
      pathways from cutaneous afferents to alpha-motoneurones during fictive locomotion
      in cats.

PMID- 19605174
TI  - Functional localization in the rabbits inferior olive determined in connection
      with the vestibulo-ocular reflex.

PMID- 19605175
TI  - Decision latency: the P3 component in auditory signal detection.

PMID- 19605176
TI  - The intracerebrally cultured 'microbrain': a new tool in developmental
      neurobiology.

PMID- 19605177
TI  - Influence of cortico-striatal afferents on striatal kainic acid neurotoxicity.

PMID- 19605178
TI  - Immunologic characterization of oligodendroglia.

PMID- 19605179
TI  - Occurrence of dopamine-containing neurons in the midbrain raphe nuclei of the
      rat.

PMID- 19605180
TI  - Axonal trajectory of single group Ia and Ib fibers in the cat spinal cord.

PMID- 19605181
TI  - Pontine and mesencephalic afferents to the central nucleus of the amygdala of the
      rat.

PMID- 19605183
TI  - The interaction of chloride, choline, noradrenaline and 5-hydroxytryptamine with
      a purified synaptic plasma membrane fraction.

PMID- 19605182
TI  - Tetanus toxin: immunocytochemical evidence for retrograde transport.

PMID- 19605184
TI  - Effects of drugs on the characteristics of cat's saccadic eye movements.

PMID- 19605185
TI  - Transposition of the soleus into the bed of the extensor digitorum longus muscle
      in the rat.

PMID- 19605186
TI  - Club endings of primary afferent fibres identified by anterograde horseradish
      peroxidase labelling. An em study.

PMID- 19605187
TI  - Direct projections from the Ediger-Westphal nucleus to the cerebellum and spinal
      cord in the cat: an HRP study.

PMID- 19605188
TI  - Thermo-sensitive neurons in preoptic and anterior hypothalamic tissue cultures in
      vitro.

PMID- 19605189
TI  - Changes in beta-receptor binding sites in rat brain after neonatal 6
      hydroxydopamine treatment.

PMID- 19605190
TI  - Effect of the delta sleep-inducing peptide (DSIP) on the sleep-wakefulness cycle
      of cats.

PMID- 19605191
TI  - Evidence for central alpha adrenoceptor stimulation as the basis of paradoxical
      sleep suppression by alpha methyldopa.

PMID- 19605192
TI  - Lack of brain specific benzodiazepine receptors on mouse primary astroglial
      cultures.

PMID- 19605193
TI  - Differential role of granule cells in the specification of synapses between
      climbing fibers and cerebellar Purkinje cells in the rat.

PMID- 19605194
TI  - The distribution of taurine, cysteinyl sulphinilic acid decarboxylase and
      crysteinyl sulphinlic acid alpha-ketoglutarate transaminase in the rat olfactory
      bulb and olfactory nucleus.

PMID- 19605195
TI  - Asparate and/or glutamate may be transmitters in hippocampal efferents to septum
      and hypothalamus.

PMID- 19605196
TI  - Multi-component accumulation of L-[(14)C]glutamate by rat spinal cord slices.

PMID- 19605198
TI  - Stress-induced increase of pineal N-acetyltransferase activity in intact rats.

PMID- 19605197
TI  - Peptidergic (VIP) nerves in the mammalian choroid plexus.

PMID- 19605199
TI  - Degradation of thyrotrophin-releasing hormone in subcellular fractions from
      different areas of the rat central nervous system.

PMID- 19605200
TI  - Imprinting to light-dark cycles or rearing in constant light affect circadian
      locomotor rhythm of mice.

PMID- 19605201
TI  - Ensheathment and myelination of regenerating PNS fibres by transplanted optic
      nerve glia.
AB  - Interactions between PNS axons and CNS glia were studied morphologically by
      transplanting optic nerves into peripheral nerves in groups of rats and mice.
      Four to 11 months after grafting, small numbers of axons from the peripheral
      nerves had penetrated the CNS grafts where they became ensheathed and myelinated
      by CNS glia. Glial protuberances observed at the CNS-PNS interfaces suggested
      that there had been an active glial response to innervation by PNS axons. These
      findings provide experimental evidence that denervated CNS glia can be
      reinnervated and form myelin.

PMID- 19605202
TI  - Three-dimensional reconstruction of specialized endoplasmic reticulum in neurons
      of the rat substantia gelatinosa.
AB  - Specializations of the agranular endoplasmic reticulum have been observed in
      neurons of the rat substantia gelatinosa. Three-dimensional models of immature
      and mature forms were reconstructed from stereomicrographs obtained with the high
      voltage electron microscope. The immature specializations consisted of two or
      more parallel, interconnected agranular cisternae with an electron dense material
      between adjacent cisternal walls. Mature specializations appeared whorl-like in
      cross-section. Throughout differentiation and maturity, the specialized agranular
      cisternae are connected to subsurface cisternae by the granular endoplasmic
      reticulum. These structures may play a role in chemical storage or synthesis.

PMID- 19605203
TI  - Small neurons in the parafascicular complex in the opossum: a golgi study.
AB  - Golgi preparations of the caudal intralaminar area in the opossum contain two
      varieties of small neurons. The first variety, the short axon cells possess
      intrinsic beaded axons and a few axon-like processes. The second type, although
      possessing certain features of the short axon cells, has a more extensive
      denritic arborization and gives rise to an axon initial segment.

PMID- 19605204
TI  - Evidence for branched subthalamic nucleus projections to substantia nigra,
      entopeduncular nucleus and globus pallidus.
AB  - The organization of subthalamic (STN) projections to the substantia nigra (SN),
      entopeduncular nucleus (EN) and globus pallidus (GP) were studied in the rat. The
      neurons projecting from the STN were identified by antidromic activation from the
      target nuclei. Most of the STN cells projecting to EN and/or GP were found to
      send an axonal branch to the SN. The existence of such branched neurons suggest
      that STN output neurons might be of only one type and influence SN, EN and GP
      synchronously.

PMID- 19605205
TI  - Cells of origin of pathways descending to the spinal cord in a lizard (Larcerta
      galloti).
AB  - The pathways descending to the spinal cord have been studied in the lizard
      Lacerta galloti with the HRP-technique. Cells of origin of such pathways have
      been demonstrated in the hypothalamus and throughout the brain stem. In the brain
      stem, besides labeled cell groups in the reticular formation and in the
      vestibular nuclear complex, labeled neurons have been found in the nucleus ruber,
      in the locus coeruleus, in the two deep cerebellar nuclei, in two somatosensory
      relay nuclei (the nucleus funiculi dorsalis and the descending nucleus of the
      trigeminus) and in two presumably parasympathetic nuclei (the nucleus of Edinger
      Westphal and the dorsal motor nucleus of the vagus).

PMID- 19605206
TI  - Cells of origin of corticopontine and corticotectal fibers in the medial and
      lateral banks of the middle suprasylvian sulcus in the cat. An experimental study
      with the horseradish peroxidase method.
AB  - Cells of origin of corticopontine and corticotectal fibers in the medial and
      lateral banks of the cat middle suprasylvian sulcus (MSs area) were identified by
      means of the retrograde axonal transport of horseradish peroxidase. Somal
      diameters of labeled cells seen in the MSs area were measured after injection of
      the enzyme in the pons and the tectum. Diameters of corticopontine and
      corticotectal neurons are 12-35 microm (mean and SD: 18.9 + or - 3.2 microm) and
      12-55 microm (mean and SD: 27.7 + or - 10.6 microm), respectively. These two
      kinds of neurons are both pyramidal in shape, located in layer V and the
      corticotectal neurons are, in general, larger and more polymorphic than the
      corticopontine cells. It thus appears that the two descending fibers originate
      from different, and independent sets of pyramidal neurons in layer V of the
      cortex.

PMID- 19605207
TI  - Axonal transport of HRP in descending tectal fibers of the pit viper.
AB  - Micro injections of 30% HRP were made into the superficial layers of the
      rattlesnake's optic tectum. The results demonstrate the presence of: an
      intertectal connection, a tectal --> contralateral medial reticular formation
      projection, a reciprocal tectal <--> ipsilateral lateral reticular formation
      projection, and a direct trigemino --> contralateral tectal projection. This
      latter projection may be related to the relay of infrared information from the
      trigeminal system to the contralateral tectum in pit vipers.

PMID- 19605208
TI  - Thalamic projections of the vestibular nuclei in the cat as revealed by
      retrograde transport of horseradish peroxidase.
AB  - Vestibulo-thalamic projections were studied in the cat by injecting horseradish
      peroxidase in different parts of the nucleus ventralis lateralis thalami (VL) and
      analyzing the distribution of the tracer in the vestibular nuclei: when it was
      injected in the dorsal part of VL, cells in the contralateral superior and medial
      vestibular nuclei were labeled, thus confirming the existence of a vestibulo
      thalamic pathway.

PMID- 19605209
TI  - Demonstration of a heavy projection of midline thalamic neurons upon the lateral
      nucleus of the amygdala of the rat.
AB  - Using a horizontal approach horseradish peroxidase (HRP) was
      microiontophoretically applied in the lateral posterior nucleus (ALP) of the
      amygdala. Retrograde labeled neurons were found in various midline and
      intralaminar thalamic nuclei and particularly in the inter-antero-medial nucleus
      (IAM) of the thalamus. The number of labeled neurons found in IAM amounted to
      more than 30% of the total brain HRP positive cells.

PMID- 19605210
TI  - Displaced ganglion cells in carp retina revealed by the horseradish peroxidase
      technique.
AB  - Displaced ganglion cells were identified in the carp retina by the retrograde
      axonal transport of horseradish peroxidase injected into the optic tectum. Cells
      in the ganglion cell layer were all labelled, while in the amacrine cell layer
      only 1/4000 cells were labelled. Because of such low population, it is unlikely
      to penetrate displaced ganglion cells by microelectrodes. The present finding
      suggests that the spiking cells frequently recorded in the inner nuclear layer
      are genuine amacrine cells.

PMID- 19605211
TI  - The role of internal pallidal segment on the initiation of a goal directed
      movement.
AB  - In monkeys performing a pointing movement, reaction times (RTs) had been studied
      after permanent exclusion or reversible cooling of the internal pallidal segment.
      The results show a significant diminution of RT in all treated animals. The role
      of the internal pallidal segment on the preparatory phase of the motor act is
      emphasized.

PMID- 19605212
TI  - Parietal neurons with dual sensitivity to real and induced movements of visual
      target.
AB  - In the parietal association area of alert monkeys, a peculiar type of visual
      tracking neurons (VT neurons) were found in the posterior part of area 7. These
      cells were excited not only by the act of tracking but also by movement of a
      frame around the stationary target fixated by the monkey. The latter stimulation
      was the same as used to evoked visual illusion of "induced movement". This dual
      sensitivity of the VT neurons to real and induced movements of the target
      suggests that these neurons are closely related to motion perception of visual
      target.

PMID- 19605213
TI  - Pepipheral input to the rat subthalamic nucleus, an electrophysiological study.
AB  - Electrophysiological experiments were carried out in acute rats in order to
      investigate the existence and organization of the peripheral inputs to the
      subthalamic nucleus (STN). The majority of the recorded STN neurons (80 127 )
      were found to respond with an initial excitation to the contralateral vibrissae
      skin area stimulation. Moreover, convergent responses were always observed since
      all these 80 units also responded to at least one of the other tested
      stimulations (ipsilateral vibrissae area and the four paws). These responding STN
      units were found to be located mostly in the lateral two thirds of the nucleus.
      This response is probably mediated by the somatosensory cortical areas since it
      was suppressed by ablation or cooling of these cortical regions.

PMID- 19605214
TI  - The acquisition of tectal positional specification in Xenopus.
AB  - During early embryogenesis before the outgrowth of the optic fibres the left eye
      blastema was removed. At the time of metamorphosis the right tectum, which has
      thus not received an optic fibre input, was surgically rotated by 180 degrees and
      the right optic nerve deflected to the rotated tectum. Between two and five
      months after the last operation the retinotectal projection was mapped
      electrophysiologically and autoradiographically. The visuotectal projection was
      found to be rotated, indicating that the ingrowing optic fibres had reached the
      same tectal areas that they would have reached had the tectum not been rotated.
      Since no retinal input reached the rotated tectum until after metamorphosis, it
      is concluded that tectal positional markers which serve as targets for the
      deployment of retinal fibres are inherent to the tectum and are generated
      independently of optic fibre input, presumably during early larval life.

PMID- 19605215
TI  - Abnormal staggerer cerebellar cell interactions and survival in vitro.
AB  - Staggerer cerebellar cells in primary monolayer cell culture exhibit less initial
      clumping and unexpectedly longer overall survival than their wild-type
      counterparts when grown in medium containing fetal calf serum. Although
      polylysine coating of substratum both reduces the amount of initial clumping and
      increases the survival of normal cells, it does not completely eliminate the
      difference between mutant and control. Such cultures exhibit the same behavior
      only when culture conditions are changed to include supplementation with horse
      serum instead of fetal calf serum in addition to the substrate coating. These
      results are discussed in terms of the site of action of the mutation.

PMID- 19605216
TI  - Melatonin in rat pineal gland and serum; rapid parallel decline after light
      exposure at night.
AB  - Melatonin content in the rat pineal decreases at night after exposure of animals
      to light, from 20 to 2 pmol/gland in 15 min. Melatonin concentration in serum
      fell precipitously in a manner almost identical to the drop in pineal melatonin
      only with a 5 min time lag. It is concluded that the rapid decrease in the pineal
      melatonin content is mainly due to an inhibited synthesis of melatonin.

PMID- 19605217
TI  - Further evidence that methergoline is a central 5-hydroxytryptamine receptor
      blocking agent.
AB  - The effects of methergoline were studied on [5-(3)H]hydroxytryptamine ([5
      (3)H]HT) and [d-(3)H]lysergic acid diethylamide ([d-(3)H]LSD) binding in rat
      cerebral cortex and on a behaviour dependent upon 5-HT receptor activity.
      Methergoline had a high affinity for both d-LSD binding sites and 5-HT binding
      sites, the affinity being 5 times higher for the d-LSD binding site. Methergoline
      also blocked the 5-hydroxytryptophane (5-HTP) and d-LSD induced head twitches in
      mice being 4 times more efficient in blocking 5-HTP induced head twitches than d
      LSD induced head twitches. The present results give evidence that methergoline is
      a postsynaptic 5-HT receptor blocking agent, an action probably related to its
      ability to bind to the antagonist site of the postsynaptic 5-HT receptor.

PMID- 19605218
TI  - Myelin composition in the central nervous system of mutant Han-Wistar rats.
AB  - Characterization of a Han-Wistar mutation (which is expressed as progressive
      spastic paresis in homozygotes) was extended to an analysis of myelin isolated
      from the brain, cerebellum and spinal cord of affected and littermate control
      rats. In all regions, the tissue content and protein composition of myelin from
      both groups of animals were similar, indicating that the synthesis of abnormal
      myelin is not the primary effect of this mutation.

PMID- 19605219
TI  - Antidromically activated direction selective ganglion cells of the rabbit.
AB  - To determine the conduction velocities and the retinofugal projections of the
      direction selective ganglion cells of the rabbit retina, these cells were
      stimulated antidromically from the chiasma opticum (CH), the lateral geniculate
      nucleus (LGN) and the superior colliculus (SC). The cells showed conduction
      velocities of 20-8 m/sec. The range of the latencies showed a significant overlap
      with the latencies of the transient and sustained ON and OFF-cells. Approximately
      25% of the cells in the rabbit's retina are described as being direction
      selective. These cells show a maximal response to the movement of a stimulus in
      the "preferred direction" but little or no response to movements in the opposite
      direction ("null direction") [1].

PMID- 19605220
TI  - Improvement of cobalt-transport in axons by complexing agents.
AB  - The use of the cobalt technique is limited by the fact that cobaltous ions travel
      within axons for a shorter distance than do other intracellular markers. In the
      present experiments different organic cobaltous complexes were tested in the
      rat's sciatic nerve. Cobaltous complexes containing ornithine, threonine, lysine
      or Girard's reagent travelled two or three times further than did the cobaltous
      ions alone. Using the lysine complex in the frog's visual system, very fine
      terminals were observed which have never been demonstrated with other techniques.
      The possible use of other metal complexes as intracellular markers are also
      discussed.

PMID- 19605221
TI  - Studies in vivo of ribonucleic acid turnover in mice (strain C57 BL/6J)
      homozygous and heterozygous for the dystrophic gene, dy(2J).
AB  - In vivo incorporation of [5-(3)H]uridine into RNA of 40-day-old mice, homozygous
      and heterozygous for the dy(2J) dystrophic allele, has been examined. Increased
      incorporation is seen in leg skeletal muscle but no increase is liver tissue.
      Determination of DNA and RNA content of the muscle tissue examined showed that
      the increased incorporation was not due to muscle volume changes that are
      associated with wasting in dystrophic muscle. The results obtained with the
      dy(2J) allele are discussed with respect to related investigation with the dy
      dystrophic allele.

PMID- 19605222
TI  - S-100 protein level alterations in the central nervous system of three
      neurological mutant mice.
AB  - S-100 protein level has been examined in parallel in brain hemispheres, pons
      medulla, cerebellum and spinal cord of three neurological mutants and of their
      normal littermates. Increased level was found in the brain of Quaking, myelin
      deficient mutant. Decreased level was found in spinal cord of Jimpey mice, also a
      myelin deficient mutant, and in all areas of Dwarf mutant, growth hormone
      deficient. On the basis of the known glial cell alterations in the myelin
      deficient mutants the results suggest the presence of S-100 protein in the two
      classes of glial cells, astrocytes and oligodendrocytes. In Dwarf mutant the
      results are consistent either with a decreased number of glial cells or with some
      kind of dependence of S-100 protein level on the presence of growth hormone.

PMID- 19605224
TI  - Effect of substituted benzamides on the cAMP system in the hypothalamus and
      striatum of the rat.
AB  - Adenylate cyclase and phosphodiesterase activities were evaluated in the striatum
      and hypothalamus of male rats after single treatment with different substituted
      benzamides (sulpiride, sultopride, tiapride, metoclopramide and bromopride) or
      chlorpromazine. None of the benzamides modifies the adenylate cyclase activity in
      the striatum but all of them stimulate this activity in the hypothalamus. The
      stimulating effect on the adenylate cyclase activity exerted by the in vitro
      addition of dopamine is not modified by the previous treatment with benzamides.
      Phosphodiesterase activity is not modified in the striatum, whereas it is
      depressed in the hypothalamus and completely inhibits the in vitro stimulating
      effect of dopamine.

PMID- 19605223
TI  - Epinephrine distribution in human brain.
AB  - The distribution of epinephrine (E) in human brain has been analyzed by a
      previously described [11] liquid chromatographic method. E, though detectable in
      most areas sampled, was found to be highly localized in those areas previously
      known to contain highest norepinephrine (NE) concentrations [4]. The regions
      found to be highest in E concentration were the ventromedial, dorsomedial,
      supraoptic and paraventricular nuclei of the hypothalamus.

PMID- 19605225
TI  - Benzodiazepine receptor binding in rat spinal cord membranes.
AB  - Using [(3)H]diazepam, benzodiazepine receptor binding has been investigated in
      rat spinal cord synaptosomal membranes. Specific [(3)H]diazepam binding is
      saturable with a K(D) of about 8 nM and a maximal number of binding sites of 0.48
      pmol/mg protein, which is about half of the density found in rat brain
      synaptosomal membranes. Using 5 benzodiazepine derivatives and amino acid
      neurotransmitters and their antagonists, no differences in specific
      [(3)H]diazepam binding to rat spinal cord and rat brain synaptosomal membranes
      were found. The results do not support the hypothesis that benzodiazepines act
      via glycine receptors in the spinal cord.

PMID- 19605226
TI  - Supression of nociceptive responses in the rat by physostigmine. Role of
      serotonin.
AB  - Physostigmine produced a dose-related suppression of nociceptive response in the
      rat, as tested by the rat tail-hot wire technique. The antinociceptive action of
      physostigmine was significantly reduced after treatment with drugs known to
      reduce brain serotonin activity. The results suggest that the antinociceptive
      action of physostigmine, in the rat, is serotonin-mediated.

PMID- 19605227
TI  - Specific [(3)H]corticosterone uptake in the hippocampus and septum varies with
      social settings in mice: Hormone-receptor autoregulation may be involved.
AB  - Specific [(3)H]corticosterone uptake in hippocampus and septum was reduced in
      socially deprived, as well as in crowding-stressed mice, in comparison with
      grouped ones. Its magnitude was related to hierarchic rank in the group but
      unrelated to agressiveness which, in turn, was unaffected by adrenalectomy and
      corticosterone replacement. A complex, regulatory interplay may exist between
      limbic specific corticosterone receptors and hypophyso-adrenal activity.

PMID- 19605228
TI  - Different times of development of tremor to harmaline and oxotremorine in
      neonatal rats.
AB  - Neonatal rats at 1-2 days after birth were injected with the tremorogenic drugs
      harmaline and oxotremorine. The onset of tremor to the drugs was significantly
      different (P < 0.01). Tremor induced by oxotremorine first appeared at day 4 and
      by day 10 was observed in every rat. Harmaline induced tremor appeared later,
      developing between days 9-12. All rats showed tremor in response to harmaline at
      day 12 and afterwards. The difference in time of onset between the response to
      the two drugs reflects different brain sites of action. The development of
      harmaline induced tremor may reflect the functional synaptic maturation of the
      olivo-cerebellar circuit.

PMID- 19605229
TI  - Reduced behavioral effectiveness of ACTH(1-24) after a second administration:
      interaction with opiates.
AB  - Repeated intraventricular administration of ACHT results in reduction of
      subsequent ACTH-induced grooming behavior. A previous injection of beta
      endorphin, (D-Phe(7))ACTH(4-10), or morphine, also reduces the behavioral
      response to a subsequent injection of ACTH. The reduction in grooming as a result
      of repeated administration is not mediated by corticosteroid feedback and can be
      eliminated by pretreatment with the opiate antagonist naloxone.

PMID- 19605230
TI  - Trunk-ocular reflex in man.
AB  - The experiments were designed to determine whether twisting of the trunk induces
      eye movements in man. The subject's head and neck were fixed firmly, and the
      chair in which the subject sat was turned along a vertical axis sinusoidally at
      about 1 4 Hz . It was found that the eye deviated horizontally in a direction
      counter to the twisting of the lower trunk. This ocular movement was accompanied
      by nystagmus. The gain (the ratio of ocular movement to chair movement) of the
      trunk-ocular reflex appeared to be about 0.5 with time lag of around 80 msec.

PMID- 19605232
TI  - Single unit study in the inferior colliculus of the house mouse (Mus musculus).
AB  - Auditory responses of single units in the central nucleus of the mouse's inferior
      colliculus with a range of best frequencies of 5-50 kHz were studied
      electrophysiologically. The threshold values to tone burst stimulation of the
      most sensitive units were in good agreement with a behavioral audiogram measured
      on animals of the same strain. The unit's best frequencies showed the same
      vertical tonotopic organization as in the inferior colliculus of other mammals.
      Most units responded only to the onset of the stimulus.

PMID- 19605231
TI  - Quantitative assessment of altered thermal sensation in patients suffering from
      cutaneous nerve disorders.
AB  - In psychophysical experiments on recognition of warm and cold stimuli delivered
      to the hand, the onset of perception was considerably delayed in patients
      suffering from traumatic lesions of cutaneous nerves or from carpal tunnel
      syndrome. This delay of perception is significantly correlated with the loss of
      discrimination ability for thermal stimuli.

PMID- 19605233
TI  - Cells of origin of propriospinal and ascending supraspinal fibers in a lizard
      (Lacerta galloti).
AB  - The location of cells of origin of propriospinal and ascending supraspinal fibers
      has been determined by injecting horseradish peroxidase (HRP) unilaterally into
      various parts of the spinal cord of the lizard Lacerta galloti. The distribution
      of retrogradely labeled cells after unilateral high spinal cord injections
      suggests that ascending supraspinal fibers are derived from neurons in the
      following areas: in the cervical intumescence in most areas of the spinal gray,
      particularly ipsilaterally, in thoracic and lumbar segments, in deeper situated
      areas, especially contralaterally. The presence of cells of origin of long
      descending propriospinal pathways has been demonstrated following HRP-injections
      into the lumbar intumescence.

PMID- 19605234
TI  - Retrograde transport of horseradish peroxidase from the preoptic-anterior
      hypothalamic region to retinal ganglion cells in quail.
AB  - Horseradish peroxidase was injected in the preoptic-anterior hypothalamic area of
      intact male quail and reacted with 3,3'-diaminobenzidine and hydrogen peroxide in
      eye sections. Cells labelled with peroxidase reaction product were found in the
      ganglion layer of the retina. One possible function of such retinal-hypothalamic
      connections might be to participate in the photosexual reflex.

PMID- 19605235
TI  - Demonstration of horseradish peroxidase and fluorescent catecholamines in the
      same neuron.
AB  - The demonstration of the presence of catecholamines and horseradish peroxidase
      (HRP) in the same neuron has been achieved by submitting vibratome sections to a
      modified glyoxylic acid fluorescence method followed by the usual procedure to
      reveal HRP. After HRP injection into the striatum or into the nucleus accumbens
      of the rat, both fluorescent dopaminergic neurons labelled with HRP and non
      fluorescent neurons labelled with HRP were observed in the substantia nigra or in
      the ventral tegmental area, respectively.

PMID- 19605236
TI  - Identification of afferent connections to cortical area 6abeta of the cat by
      means of retrograde horseradish peroxidase transport.
AB  - Ten cats were injected in cortical area 6abeta with HRP. The distribution of the
      cortico-cortical and thalamo-cortical afferent neurones were analysed. In the
      ipsilateral cortex, labelled cells were found in the following gyri: sigmoid,
      coronal, anterior ectosylvian, anterior suprasylvian, and orbital. In the
      contralateral cortex, HRP-positive neurones were found only in zones homotopic to
      the injection site. In the thalamus, the most heavily labelled nuclei were
      ventralis lateralis and ventralis medialis, while ventralis anterior, medialis
      dorsalis, and the intralaminar nuclei were labelled to a lesser extent. No
      labelled cells were found in contralateral thalamic nuclei.

PMID- 19605237
TI  - Localization of catecholamine fluorescence and retrogradely transported
      horseradish peroxidase within the same nerve cell.
AB  - A technique that enables both catecholamines (CA) and horseradish peroxidase
      (HRP) to be localized in the same cell is described. HPR was injected into the
      spinal cord and three days later rabbits were perfused with a mixture of 4%
      formaldehyde and 0.5% glutaraldehyde to produce a fluorescence reaction in CA
      containing cells. Subsequently, HRP was localized in the same neurons using
      tetramethylbenzidine.

PMID- 19605238
TI  - Regional sympathectomy induced by intra-arterial 6-hydroxy-dopamine.
AB  - Single intra-carotid injections of 5-15 mg of 6-OH-DA HBr in adult cats reduced
      or abolished the responses of the ipsilateral nictitating membrane to electrical
      stimulation of post-ganglionic sympathetic nerves and intra-carotid injections of
      tyramine; the responses of the contralateral nictitating membrane to the same
      stimuli remained normal. One to five days after 6-OH-DA, the ipsilateral
      nictitating membranes, unresponsive to sympathetic stimulation, were
      hypersensitive to i.v. injections of adrenaline or noradrenaline. The advantages
      of regional over systemic chemical sympathectomy are discussed.

PMID- 19605239
TI  - Effects of 6-hydroxy-dopamine on carotid body chemosensory activity.
AB  - 6-OH-DA HBr 5-25 mg injected into one common carotid artery of pentobarbitone
      anesthetized cats, induced a transient inhibition of chemosensory discharges
      recorded from the ipsilateral carotid nerve, but did not change chemosensory
      frequency during spontaneous ventilation, periodic deep breaths and asphyxia.
      Chemosensory activities recorded simultaneously from both carotid nerves showed
      no differences in their inhibitory responses to dopamine and their excitatory
      responses to NaCN, up to 48 h after the injections of 6-OH-DA. It is concluded
      that 6-OH-DA acts initially as a dopamine analogue, and does not impair
      subsequent carotid body chemoreception or dopamine-induced inhibition, as doses
      producing abolition of noradrenergic transmission.

PMID- 19605240
TI  - Uptake of (3)H labeled synthetic progestin by rat brain and pituitary. A
      radioautography study.
AB  - The distribution of cells concentrating R 5020, a potent synthetic progestin, in
      the brain and pituitary of estrogen-primed ovariectomized rat was investigated by
      radioautography. In the brain, radioactivity was found concentrated in nuclei of
      neurons in the preoptic region (nucleus (n.) preopticus pars suprachiasmatica, n.
      preopticus periventricularis, n. preopticus medialis) and in the medio basal
      hypothalamus (n. ventromedialis and n. arcuatus). In the anterior pituitary, a
      significant number of labeled cells was observed.

PMID- 19605241
TI  - Unilateral ovariectomy-induced luteinizing hormone-releasing hormone content
      changes in the two halves of the mediobasal hypothalamus.
AB  - The luteinizing hormone-releasing hormone (LHRH) content of the two halves of the
      mediobasal hypothalamus (MBH) has been studied two weeks after unilateral or
      bilateral ovariectomy (OVX) in the rat. In control animals, the LHRH content of
      the right-side MBH was higher than that of the left side. Right-side OVX induced
      a significant increase in LHRH content on the right-side MBH while left-side OVX
      was followed by elevated LHRH content on the left-side MBH. In contrast,
      bilateral OVX induced a significant decrease on the right-side MBH. The
      observation that unilateral OVX induced increased LHRH content in the ipsilateral
      half of the MBH to OVX, supports the view that a neural pathway might connect the
      ovary and the MBH.

PMID- 19605242
TI  - ACTH controls [(3)H]dopamine uptake in the adrenal chromaffin cell.
AB  - Effect of hypophysectomy on the disposition of [(3)H]dopamine-derived
      radioactivity in the mouse adrenal medulla was examined by autoradiography.
      Chromaffin cells, both A and NA type, incorporated less radioactivity in the
      hypophysectomized mice (50 days after operation) than in normal control mice:
      this decrease in the [(3)H]dopamine uptake was restored by intraperitoneal
      injection of ACTH (for 26 days; starting from 24th day after hypophysectomy; 40
      mug/gbw/day). In the control mice chromaffin cells near the cortico-medullary
      junction showed a higher radioactivity than those in the center: hypophysectomy
      obscured this specific distribution pattern which reappeared after ACTH
      treatment.

PMID- 19605243
TI  - The distribution of vasopressin and oxytocin in the rat brain.
AB  - Since vasopressin and oxytocin might be involved in processes of storage and
      retrieval of information in rats, the distribution of these hormones within the
      central nervous system was measured employing sensitive and specific
      radioimmunoassays in combination with an extraction method using Vycor glass
      powder. Vasopressin was detected in hypothalamus, amygdala, septum, hippocampus,
      nucleus parafascicularis and medulla oblongata of Wistar and Brattleboro rats,
      heterozygous for diabetes insipidus. It was not detectable in samples of
      Brattleboro rats, homozygous for diabetes insipidus. Oxytocin was found in
      hypothalamus, septum and nucleus parafascicularis of Wistar rats in lower amounts
      than vasopressin while it was present in higher amounts in the medulla oblongata.
      The extensive distribution of these hormones in the rat brain suggests a possible
      role in a variety of central nervous system processes rather than solely in the
      expression of acquired behavior.

PMID- 19605244
TI  - The basolateral amygdaloid projections to the neocortex in the cat.
AB  - Retrogradely labeled cells have been found in the ipsilateral basolateral nucleus
      of the amygdala (BL) following injections of horseradish peroxidase (HRP) in
      various neocortical areas in the cat. The number of labeled neurons was small in
      the majority of the cases; however the amygdaloid projections to the prefrontal,
      anterior cingulate, insular and posterior sylvian cortices appeared heavier. HRP
      injections in the parietal associative and visual areas did not result in labeled
      cells in the amygdala. The present data suggest that the cortical projections
      arising from BL are more widely distributed than previously reported.

PMID- 19605245
TI  - Afferent projections to A10 dopaminergic neurones in the rat as shown by the
      retrograde transport of horseradisd peroxidase.
AB  - Following the microiontophoresis of horseradish peroxidase to the ventral
      tegmental area of Tsai, neurones labelled by retrograde transport of the enzyme
      were observed in a large number of sites throughout the brain. In addition to
      confirming previously described afferents, these studies suggest so far unknown
      systems projecting to the area from cerebral cortex, hypothalamus, amygdala,
      thalamus, superior colliculus, substantia nigra, parabrachial nuclei and medulla
      oblongata.

PMID- 19605246
TI  - Retzius-Cajal or Cajal-Retzius cells?

PMID- 19605247
TI  - Editorial.

PMID- 19605248
TI  - Conversion of lipotropic peptides by purified cathepsin D of human pituitary:
      release of gamma-endorphin by cleavage of the Leu(77)-PHE(78) bond.
AB  - Cathepsin D (EC 3.4.3.23) purified from human putuitary by affinity
      chromatography on pepstatin-Sepharose cleaved human beta-endorphin (LPH 61-91) at
      the Leu(77)-Phe(78) bond after incubation at pH 3.2 for 1-3. Incubation with
      smaller lipotropic fragments (enkephalin, alpha-endorphin, gamma-endorphin) did
      not lead to further degradation. Cleavage sites were identified following the
      separation of danyslated or iodinated peptides on polyamide sheets accompanied by
      N-group determination, or following slab-gel electrophoresis of the iodinated
      peptides. Cleavage at the above site was blocked using an analog containing D
      Leu(77). Breakdown of porcine beta-lipotropin (LPH 1-91) was slower and required
      an 18 h incubation. A product LPH 1-77 was tentatively identified based in part
      on its mobility on slab gels as compared to beta-LPH and beta-endophine and by N
      group determination of cleavage products.

PMID- 19605249
TI  - A new method to quantify catecholamine stores visualized by means of the Falck
      Hillarp technique.
AB  - A new method has been developed by which it is possible to quantitate specific
      catecholamine fluorescence in the CNS. The method is based on an elaboration by
      means of Kodalith plates of microphotographs taken from suitable Falck-Hillarp
      preparations. This method has been applied to study DA fluorescence decay in the
      caudatus after tyrosine hydroxylase inhibition. The method is reliable since the
      half-life obtained for DA turnover in the caudatus is very close to similar
      values obtained by means of both microfluorimetry and mass fragmentography.

PMID- 19605250
TI  - Identification of thalamic projection cells in the rat cuneate nucleus: a light
      and electron microscopic study using horseradish peroxidase.
AB  - Cuneo-thalamic projection cells in the rat were identified after injection of
      horseradish peroxidase into the contralateral thalamic nucleus ventralis
      posterolateralis. By light microscopy, labelled cells were 16-20 microm in
      diameter, round or oval in shape, distributed throughout the cuneate nucleus and
      concentrated in the region of the obex. By electron microscopy, reaction products
      were found in two different types of neuronal profile. Most were 16-19 microm in
      diameter, round or slightly oval, with a smooth nucleus, small stacks of rough
      endoplasmic reticulum and many axo-somatic synapses. The remaining profiles were
      oval, 14-19 microm in long diameter, with a flattened, indented nucleus and very
      few axo-somatic synapses.

PMID- 19605251
TI  - Effects of local cobalt chloride injection on lateral spread of signals in fish
      (roach) retina.
AB  - There is extensive spatial summation in electrical responses of both horizontal
      and amacrine cells of the fish retina. The effect of locally perfused cobalt
      chloride on the lateral spread of signals along the layers of these interneurones
      has been studied in the roach (Rutilus rutilis) retina. It is shown that lateral
      transmission is blocked in amacrine but not in horizontal cells and this result
      is examined in relation to the synaptic coupling of the interneurones.

PMID- 19605252
TI  - Retinodiencephalic projections from compound eyes in Xenopus.
AB  - The contralateral diencephalic projections from compound eyes, made by the early
      embryonic fusion of two nasal (NN), two temporal (TT) or two ventral (VV) retinal
      fragments, have been studied in young toads using [(3)H] proline autoradiography.
      After intraocular isotope injection into compound eyes which represent only half
      of the normal naso-temporal or dorso-ventral sets of ganglion cells, the total
      projection to the nucleus of Bellonci (NB), corpus geniculatum thalamicum (CGT)
      and pretectal nucleus (PN) was found to be the same as in normal eyes. These
      results show the spreading of a half-retinal projection to the whole of the
      diencephalic visual centres, indicating that the pattern of retinodiencephalic
      projections may be modified during embryogenesis.

PMID- 19605253
TI  - Interaction between receptive field halves of cells in area 18 of the cat's
      visual cortex.
AB  - Interaction between receptive field halves has have investigated in cells from
      area 18 of the visual cortex of cats light anesthestised with N(2)O/O(2)
      supplemented with pentobarbitone. Interaction within receptive field halves may
      be facilitatory additive, partially additive, or subtractive, and the
      organization in one half-field is not predictable from that in the other.
      Interaction between half-fields may be facilitatory, additive, partially
      additive, or subtractive and can not be predicted from interaction within halves.

PMID- 19605254
TI  - Autroradiographic demonstration with 2-[(14)C]deoxyglucose of frequency
      selectivity in the auditory system of cats under conditions of functional
      activity.
AB  - 2-[(14)C]deoxyglucose was injected into 3 cats, each of whom was presented with a
      tone of a different frequency under controlled auditory conditions. Clear
      selective labelling was observed in autoradiographs of the cochlear nucleus,
      parts of the superior olivary complex, the nuclei of the lateral lemniscus and
      the inferior colliculus. No selective labelling was observed in autoradiographs
      of the medial geniculate body and the auditory cortex. The labelling observed in
      the cochlear nucleus and the inferior colliculus was in agreement with previous
      studies of both the physiology and anatomy of these regions and for the first
      time provides an anatomical demonstration of the organization of frequency
      selectivity under conditions of functional activity.

PMID- 19605255
TI  - Location of lumbar preganglionic sympathetic neurones in the cat.
AB  - In the cat the distribution and projection of lumbar (L1-L4) preganglionic
      sympathetic neurones (PSNs) has been investigated with the horseradish peroxidase
      (HRP) technique. Following an HRP-injection into a lumbar sympathetic trunk
      ganglion, PSNs were found in the ipsilateral spinal cord in lamina VII, specially
      in its lateral and intermediate parts. In the medial region HRP positive cells
      were more frequently observed when the central, cut end of the ramus communicans
      albus was placed into HRP. HRP injection into the coeliac and lower mesenteric
      ganglia labelled lateral PSNs, but rarely medial ones. In the cranio-caudal
      direction, the PSNs projected over several segments via intraspinal and
      extraspinal pathways.

PMID- 19605256
TI  - Peripheral innervation by migrating neuroblasts in the chick embryo.
AB  - Horseradish peroxidase (HRP) was injected into the mandibular process of the
      first visceral arch in chick embryos of 3-6 days of incubation. On days 3 1 2 , 4
      and 4 1 2 of incubation, this procedure resulted in granular reaction product in
      neuroblasts of the lateral trigeminal nucleus and in soma and processes of
      neuroblasts in the process of migrating from the medial column to form the
      lateral nucleus. On days 5 and 6 of incubation, similar labeling was found in
      cells migrating from the lateral nucleus dorsal to form the dorsal trigeminal
      nucleus. This is the first clear demonstration of the extent of differentiation
      which may take place during neurogenesis prior to the completion of migration.

PMID- 19605257
TI  - Uptake and subsequent retrograde axonal transport of nerve growth factor (NFG)
      are not influenced by neuronal activity.
AB  - NFG is taken up by adrenergic nerve terminals by a highly efficient and selective
      mechanism and is subsequently transported to the perikaryon by retrograde axonal
      transport. Neither enhanced (cold stress) nor reduced (decentralization,
      ganglionic blocking agents) neuronal activity affects this mechanism. In
      contrast, the non-specific uptake followed by retrograde axonal transport of
      macromolecules, which depends on excessively high concentrations of these
      compounds in the vicinity of the corresponding nerve terminals, is enhanced by
      neuronal activity.

PMID- 19605258
TI  - Dendritic dopamine: studies on the release of endogenous dopamine from
      subcellular particles derived from dendrites of rat nigro-striatal neurons.
AB  - During subcellular fractionation of rat substantia nigra, the dendrites of the
      nigro-striatal neurons give rise to particles as terminals do. Release of
      endogenous dopamine from these particles could be demonstrated with amphetamine
      but not with potassium. Under identical incubation conditions, subcellular
      particles derived from the terminal area showed a marked release of endogenous
      dopamine with both amphetamine and potassium. Also in contrast to the particles
      from terminals, dendritic particles lost their major content of dopamine during
      preincubation. The results favor the concept of dendritic dopamine release, but
      emphasized the difference between dendrites and terminals of the nigro-striatal
      neurons.

PMID- 19605259
TI  - Effects of post- and pre-synaptic snake venom neurotoxins on chloride and choline
      association with synaptic plasma membranes in vitro.
AB  - The association of chloride-36 and [(3)H]choline with an isolated presynaptic
      plasma membrane fraction (SPM) was investigated. Choline interaction at low trans
      choline (1 microM) concentration was hemicholinium-3 sensitive and inhibited by
      the presynaptically active snake neurotoxins, taipoxin, Notechis II-5, Enhydrina
      schistosa myotoxin and beta-bungarotoxin while the post-synaptic toxin alpha
      bungarotoxin had no effect on choline interaction. Chloride interaction was not
      affected significantly by the toxins, thereby suggesting that gross lysis of the
      SPM does not account for their inhibitory effects on choline interaction with the
      SPM.

PMID- 19605260
TI  - Trigeminal projections to cerebellar tactile areas in the rat-origin mainly from
      n. interpolaris and n. principalis.
AB  - Four new tactile areas in the cerebellar cortex (crus I, crus II, paramedian
      lobule and uvula) have recently been described in the rat. Ipsilateral orofacial
      regions are chiefly represented in these areas. Our study of trigeminocerebellar
      afferents to these areas using the HRP retrograde tracing technique shows that
      they almost all arise in the interpolar and principal trigeminal nuclei mostly
      from the ipsilateral side. No labelled cells were found in the mesencephalic or
      caudal trigeminal nuclei after large cerebellar injections and the few labelled
      cells in n. oralis were found in the dorsomedial tip of that nucleus.

PMID- 19605261
TI  - Effect of pinealectomy, binding, castration and melatonin on nerve growth factor
      levels in the submaxillary glands of mice.
AB  - The effects of blinding alone or in combination with pinealectomy, castration and
      melatonin treatment on nerve growth factor (NGF) in submaxillary glands of mice
      were tested. Both pinealectomy and melatonin (placed subcutaneously in beeswax)
      treatment caused a marked reduction in NGF specific biological activity, esterase
      activity, and beta-protein recovered from the submaxillary glands. Castrated mice
      also exhibited depressed levels of NGF in the salivary glands.

PMID- 19605262
TI  - Cerebellar cGMP varies with motor function and respiratory gas exchange.
AB  - Paralysis of rats with d-tubocurarine decreased cerebellar guanosine 3': 5'
      cyclic monophosphate (cGMP) content to about one third of normal values when
      arterial oxygen and carbon dioxide were maintained at normal values. In addition,
      altering arterial carbon dioxide tensions in these paralyzed rats revealed that
      cerebellar cGMP was inversely related to arterial carbon dioxide tension, and
      that this relationship could be blunted by increasing arterial oxygen tension. It
      is possible that part of the decrease in cerebellar cGMP content by CNS
      depressants observed in several species in many laboratories may be simply
      secondary to the decreased motor function and/or respiratory depression produced.

PMID- 19605263
TI  - Retrograde transport of horseradish peroxidase in the rat's brain during
      halothane anesthesia.
AB  - The horseradish peroxidase (HRP) method was used to study the effect of halothane
      anesthesia on retrograde transport in the central nervous system. Rats received
      neostriatal injections of 30% HRP (0.3 microl) and were placed in inhalation
      chambers perfused with air or air containing 1% halothane for up to 24 h.
      Subsequently, the brain were examined at rostro-caudal levels of the presence and
      distribution of HRP-containing cells. The number and distribution of HRP-labelled
      cells appearing at each cranial level were compared in control and halothane
      anesthetized animals as a function of time. The results suggest that retrograde
      transport in the central nervous system is unaffected during halothane
      anesthesia.

PMID- 19605264
TI  - Horseradish peroxidase tracing of visceral efferent and primary afferent pathways
      in the cat's sacral spinal cord using benzidine processing.
AB  - Sacral afferent and preganglionic efferent neurons were labelled by applying
      horseradish peroxidase (HRP) to the central end of the transected pelvic nerve.
      Preganglionic cells were evident as a narrow band of cells extending from the
      intermediolateral region dorsomedially beneath the dorsal horn. Their dendrites
      were located primarily within the nucleus but also projected into the
      dorsolateral funiculus, along the lateral edge of the dorsal horn and to dorsal
      commissure. Labelled primary afferent axons and/or terminals were detected in
      Lissauer's tract and in the marginal zone of the dorsal horn extending from the
      apex ventrally along its lateral edge into the dorsal region of the autonomic
      nucleus. These observations suggest that sacral preganglionic neurons may receive
      monosynaptic connections from pelvic nerve afferents.

PMID- 19605265
TI  - Anterograde and retrograde transport of horseradish peroxidase isoenzymes in the
      retino-tectal fibres of xenopus larvae.
AB  - Commercial horseradish peroxidase (HRP) was separated into basic and acidic
      isoenzyme fractions. The ability of each of these two fractions to be taken up
      and transported by nerve vells was tested in the retino-tectal tract of Xenopus
      laevis at midlarval stages. HRP isoenzymes were injected with a glass
      micropipette into the eye, while scratching the optic disc to break the axons of
      ganglion cells leaving the retina. Both basic and acidic HRP were taken up by
      broken optic fibres and transported anterogradely. The same HRP preparations were
      delivered to the nerve endings of retinal ganglion cells by injecting them into
      the optic tectum. Uptake and retrograde transport could be demonstrated with
      basic HRP, but not with acidic HRP. Results are schematically shown in Fig. 3.
      The different behaviour of HRP isoenzymes could be exploited in neuroanatomical
      tracing techniques.

PMID- 19605266
TI  - Some retrohippocampal afferents to the entorhinal cortex. Cells of origin as
      studied by the HRP method in the rat and mouse.
AB  - Small HRP injections were made in the medial (MEC) and lateral entorhinal cortex
      (LEC) of rat and mouse. Injections in the MEC produced bilateral labeling of
      cells in layers II and III of the presubiculum as well as in the ipsi- and
      contralateral parasubiculum. There was no detectable transport of HRP to cells in
      pre- and parasubiculum following similar injections in the LEC. Injections in the
      deep layers (IV-VI) of MEC and LEC caused labelling of cells in the ipsilateral
      subiculum.

PMID- 19605267
TI  - Postnatal ontogenesis of potentials elicited in the barrelfield of mice by
      stimulation of the maxillary nerve.
AB  - Evoked potentials (laminar analysis and latencies) and unit discharges upon
      electrical stimulation of the maxillary branch of the trigeminal nerve are
      studied in mice between postnatal days (PN) 8 and 20. Evoked potentials are
      negative at the surface of the cortex until PN 16. Latencies reach adult values
      by the end of the third postnatal week. Comparison with rats shows that mice are
      relatively less mature than rats at same postnatal ages. A comparison of
      electrophysiological events and anatomical data shows that between PN 8 and 10
      electrical activity is limited to the marginal layer and the outer part of the
      cortical plate. Layer IV, the layer than contains the barrels, becomes active
      after PN 12. The subplate layer is found active after PN 16.

PMID- 19605268
TI  - Sustained cortical potentials evoked in humans by binocularly correlated,
      uncorrelated and disparate dynamic random-dot stimuli.
AB  - On-line computer generated random-dot targets ('Julesz patterns') were alternated
      every 720 msec between binocular correlation (percept: flat) and uncorrelation
      (percept: wooly) or partial disparity (percept: depth). Cortical evoked
      potentials recorded between anterior and posterior electrodes showed sustained
      late responses (peaks 200-400 msec), anteriorly negative for correlation and
      positive for uncorrelation or disparity, in all 13 subjects used. Shift of
      attention from one to the other stimulus condition and random stimulus intervals
      did not change the results.

PMID- 19605269
TI  - Neuronal activity in medial geniculate body following single semicircular canal
      stimulation.
AB  - Unit activity of medial geniculate body (MGB) neurons was recorded in curarized
      guinea pigs following separate thermal stimulation of single separate thermal
      stimulation of single semicircular canals. The same neurons were also tested with
      acoustic stimuli (clicks). Convergence on MGB units of inputs arising from
      several (2-6) canals was observed. Convergence of acoustic and vesticular
      influences was also demonstrated. After labyrinthine stimulation MGB neurons
      usually displayed inhibitory responses and, less frequently, activation. Clicks
      induced brief burst of activity. Our data indicate the existence of a wide
      vestibular projection in the MGB.

PMID- 19605270
TI  - Paraventricular nucleus connections to spinal cord and pituitary.
AB  - In rats anesthetized with pentobarbital or a mixture of urethane and chloralose,
      horseradish peroxidase (HRP) was injected into the intermediolateral column of
      the spinal cord (Th7 and Th9) or the posterior pituitary lobe. HRP positive cells
      were found mainly in the dorsomedial part of the paraventricular nuclease (PVN)
      of the spinal injected animals. These cells are large in size and are bipolar or
      multipolar. On the other hand, those in the pituitary injected animals were
      predominantly localized in the dorsolateral cap of the PVN. These latter cells
      are more rounded, have fewer projections, and are the same size as those in the
      dorsomedial part of the PVN.

PMID- 19605271
TI  - Immunocytochemical evidence that the same neurons in the human infundibular
      nucleus are stained with anti-endorphins and antisera of other related peptides.
AB  - Neurons immunoreactive with anti-beta-endorphin can be detected in the
      infundibular region of human fetal hypothalami from the 11th week of development.
      In the human adult, neurons stained with anti-beta-endorphin are located in the
      infundibular nucleus and are also stained with anti(17-39) ACTH. Their fibers
      terminate in contact with non/immunoreactive perikarya or close to vessels of the
      pituitary stalk. The neurons most reactive with anti(17-39)ACTH or anti-beta
      endorphin are also immunoreactive with anti-alpha-MSH, anti-beta-MSH, anti-alpha
      endorphin, anti(1-24)ACTH or anti-beta-LPH. These results suggest that a molecule
      similar to pro-opiocortin of fragment(s) of it is secreted by these neurons.

PMID- 19605272
TI  - Catecholamine concentration of various brain nuclei of the rat as affected by
      ACTH and corticosterone.
AB  - The acute effect of ACTH and corticosterone on catecholamine concentration of
      individual brain nuclei has been examined. ACTH significantly increased the
      noradrenaline (NA) content in the locus coeruleus, and decreased it in the
      ventromedial and arcuate nuclei. No change was observed after ACTH in the
      dopamine (DA) concentrations of the mentioned areas and in the catecholamine
      level of the mamillary body, hippocampus, medial habenular nucleus and of the
      pituitary. Corticosterone increased the NA content of the supraoptic nucleus and
      the NA and DA levels in the median eminence, while it did not affect the amine
      concentrations in the locus coeruleus.

PMID- 19605273
TI  - Effect of neutransmitters on in vitro release of luteinizing-hormone-releasing
      hormone from the mediobasal hypothalamus of male rats.
AB  - Effects of neurotransmitters on in vitro release of lutein-hormone-releasing
      hormone (LHRH) from fragments of hypothalamic tissue were investigated. Neither
      acetylcholine (ACh) or histamine (HA) at concentrations of 10(-7) and 10(-5) M,
      or GABA at 10(-7) to 5 x 10(-5) M affected LHRH release from mediobasal
      hypothalamic (MBH) fragments or the organum vasculosum of the laminae terminalis
      (OVLT). In contrast, serotonin (10(-7) and 10(-5) M) significantly inhibited the
      release of LHRH from the MBH but not from the OVLT. This response to serotonin (5
      HT) is no longer observed in presence of methiothepin, a 5-HT receptor
      antagonist. The present results confirm in vivo data suggesting that the
      inhibitory effect of serotonin on the release of LHRH from median eminence
      involves a direct action on neurosecretory nerve-endings.

PMID- 19605274
TI  - Glutamine and glutamate as precursors of the releasable pool of gaba in brain
      cortex slices.
AB  - The release of labeled GABA, synthesized from [(14)C]glutamine and from
      [(14)C]glutamate, was studied in mouse brain cortex slices. The spontaneous
      release of radioactive GABA derived from glutamate was higher than that of GABA
      synthesized from glutamine. In contrast, depolarization by 48 mM K(+) notably
      stimulated the release of GABA synthesized from glutamine but did not affect
      significantly the release of GABA formed from glutamate. It is concluded that
      glutamate is a better precursor than glutamine of the GABA pool spontaneously
      released, whereas the reverse is true for the pool releasable by K(+)
      depolarization. The release of [(14)C]glutamate was stimulated by K(+)
      depolarization both when it was exogenously supplied and when it was derived from
      [(14)C]glutamine.

PMID- 19605275
TI  - Glutamine as precursor for the GABA and glutamate trasmitter pools.
AB  - Pigeon optic tectum slices were incubated in [(3)H] glutamine in order to label
      the glutamate and GABA pools. 47 mM potassium chloride induced a calcium
      dependent release of [(3)H] glutamate and [(3)H] GABA. This indicates that
      glutamine is an efficient precursor of the releasable glutamate and GABA pools
      and supports the view that both amino acids play a role as neurotransmitters in
      the optic tectum.

PMID- 19605276
TI  - Phenobarbital: concentration-dependent biphasic effect on aplysia burst-firing
      neurons.
AB  - The effects of sodium phenobarbital (PNB) were tested on bursting pacemaker
      neurons in Aplysia. At low concentrations, PNB increased the slow oscillations of
      membrane potential that underline the bursting response. At higher concentrations
      the oscillations were suppressed and blocked. Under voltage-clamp conditions it
      was found that the increased slow-wave activity with low concentrations of PNB
      was due to an increase in the slow inward current that is carried primarily by
      Ca(2+) ions. The results suggest that PNB has a concentration dependent biphasic
      effect on Ca(2+) conductance mechanisms and illustrate the need for caution when
      comparing the effects of PNB between a variety of preparations.

PMID- 19605277
TI  - Ethanol and acetaldehyde levels in cerebrospinal fluid during ethanol oxidation
      in the rat.
AB  - The in vivo concentrations of ethanol and acetaldehyde were measured in
      peripheral blood and cerebrospinal fluid (CSF) of rats during 4 h after oral
      administration of 3 g ethanol/kg body wt. During the first 120 min of the
      experiment the concentration of ethanol in CSF was significantly higher than in
      peripheral blood. The concentration of acetaldehyde in blood and CSF were the
      same at 30 min, but throughout the remainder of the experiment the concentration
      of acetaldehyde in CSF was significantly lower than in the peripheral blood.
      These results show that the concentrations of ethanol and acetaldehyde in the
      peripheral blood do not quantitatively reflect the ethanol and acetaldehyde
      levels in the brain and further support the existence of a mechanism limiting the
      entry of acetaldehyde into the brain.

PMID- 19605278
TI  - Immunofluorescent localization of dopamine-beta-hydroxylase in small intensely
      fluorescent cells of the rat superior cervical ganglion.
AB  - Serial sections of the superior cervical ganglion of newborn and adult rats have
      been treated alternatively with fluorescent labelled antibodies to dopamine-beta
      hydroxylase ( (DBH), or with glyoxylic acid. Two different cell types could be
      distinguished: (1) a small intensely fluorescent (SIF)-cell majority
      demonstrating a bright glyoxylic acid-induced fluorescence but no DBH-positive
      fluorescence; (2) a minor cell population being fluorescent following both
      treatments. The findings indicate the presence of norepinephrine (and/or
      epinephrine)-containing SIF-cells in the rat superior cervical ganglion.

PMID- 19605279
TI  - Regional distribution of met-enkephalin within the amygdaloid complex and bed
      nucleus of the stria terminals.
AB  - The distribution of met-enkephalin (Met-E) within the amygdaloid complex and bed
      nucleus of the stria terminalis has been studied using a sensitive and highly
      specific radioimmunoassay. Particularly high levels of Met-E were found in the
      central nucleus of the amygdala. Large amounts of Met-E were also found in the
      various subdivisions of the bed nucleus of the stria terminalis (BST). These
      results are in good agreement with immunohistochemical data.

PMID- 19605281
TI  - Topology of the pathways to the inferior olive as ? study in cat.

PMID- 19605280
TI  - Opiate effects on aversive midbrain stimulation in rats.
AB  - Morphine blocked decremental bar pressing of rats to escape electrical
      stimulation of aversive midbrain sites. These sites included the dorsal central
      gray area (DCG), the ventral reticular formation (VRF) and the lateral tegmentum
      (LT). Naloxone, which had no effect alone, blocked the morphine effects of all
      three aversive sites.

PMID- 19605282
TI  - Electrophysiological study of the nigro-tectal pathway in the rat.

PMID- 19605283
TI  - Photomechanical changes in the retina and choroid of guinea pigs, Cavia
      porcellus.

PMID- 19605284
TI  - Response properties of vestibular afferents in alert cats during optokinetic and
      vestibular stimulation.

PMID- 19605285
TI  - Effect of neonatal unilateral eye enucleation in the chick.

PMID- 19605287
TI  - Perforant path transections protect hippocampal granule cells from kainate
      lesion.

PMID- 19605286
TI  - Responses to active and passive wrist rotation in area 5 of awake monkeys.

PMID- 19605288
TI  - Absence of apparent cell pH variations during hypoxia in the carotid body
      chemoreceptors in vitro.

PMID- 19605289
TI  - Innervation of forebrain regions by medullary noradrenaline neurons, a
      biochemical study in cats with central tegmental tract lesions.

PMID- 19605290
TI  - Monosynaptic inputs to lumbar interneurons from the lateral vestibulospinal tract
      and the medial longitudinal fasciculus.

PMID- 19605291
TI  - Temperature-responsive neurones in the midbrain raphe region of rabbits.

PMID- 19605292
TI  - Parasympathetic neuronal survival induced by factors from muscle.

PMID- 19605293
TI  - Evidence for identified dopamine motor neurons to the gill of Aplysia.

PMID- 19605294
TI  - Relations between various fiber groups of vagal and splanchnic nerves and gastric
      motility in rats.

PMID- 19605295
TI  - Fusimotor responses to volleys in joint and interosseous afferents in the cat's
      hindlimb.

PMID- 19605296
TI  - A new somatostatinergic system in the mammalian spinal cord.

PMID- 19605297
TI  - Facilitation of synaptic activity in the frog spinal cord produced by 4
      aminopyridine.

PMID- 19605299
TI  - Reduced cerebrospinal fluid formation through cholinergic mechanisms.

PMID- 19605298
TI  - Pituitary modulation of sulpiride action in the central nervous system of the
      rat.

PMID- 19605300
TI  - The mode of action of enkephalins in the guinea-pig myenteric plexus.

PMID- 19605301
TI  - Distribution of ganglioside synthetizing enzymes in rat brain: increased activity
      of galactosyl but not galactosaminyl transferase in the adult olfactory bulbs.

PMID- 19605302
TI  - Temporal distributions of delta wave sleep and rem sleep during recovery sleep
      after 12-h forced wakefulness in dogs; similarity to human sleep.

PMID- 19605303
TI  - Spermidine: a constituent of the myelin sheath?

PMID- 19605304
TI  - Are amino acid patterns necessarily abnormal in epileptic brains? studies on the
      genetically seizure-susceptible rat.

PMID- 19605305
TI  - Cerebrovascular permeability changes induced by radiopaque contrast substances in
      various areas of rabbit brain.

PMID- 19605306
TI  - Electrical conductivity and permittivity of murine myocardium.
AB  - A classic problem in traditional conductance measurement of left ventricular (LV)
      volume is the separation of the contributions of myocardium from blood.
      Measurement of both the magnitude and the phase of admittance allow estimation of
      the time-varying myocardial contribution, which provides a substantial
      improvement by eliminating the need for hypertonic saline injection. We present
      in vivo epicardial surface probe measurements of electrical properties in murine
      myocardium using two different techniques (a digital and an analog approach).
      These methods exploit the capacitive properties of the myocardium, and both
      methods yield similar results. The relative permittivity varies from
      approximately 100,000 at 2 kHz to approximately 5000 at 50 kHz. The electrical
      conductivity is approximately constant at 0.16 S/m over the same frequency range.
      These values can be used to estimate and eliminate the time-varying myocardial
      contribution from the combined signal obtained in LV conductance catheter
      measurements, thus yielding the blood contribution alone. To study the effects of
      albumin on the blood conductivity, we also present electrical conductivity
      estimates of murine blood with and without typical administrations of albumin
      during the experiment. The blood conductivity is significantly altered (p <
      0.0001) by administering albumin (0.941 S/m with albumin, 0.478 S/m without
      albumin).

PMID- 19605307
TI  - Development of an autonomous biological cell manipulator with single-cell
      electroporation and visual servoing capabilities.
AB  - Studies of single cells via microscopy and microinjection are a key component in
      research on gene functions, cancer, stem cells, and reproductive technology. As
      biomedical experiments become more complex, there is an urgent need to use
      robotic systems to improve cell manipulation and microinjection processes.
      Automation of these tasks using machine vision and visual servoing creates
      significant benefits for biomedical laboratories, including repeatability of
      experiments, higher throughput, and improved cell viability. This paper presents
      the development of a new 5-DOF robotic manipulator, designed for manipulating and
      microinjecting single cells. This biological cell manipulator (BCM) is capable of
      autonomous scanning of a cell culture followed by autonomous injection of cells
      using single-cell electroporation (SCE). SCE does not require piercing the cell
      membrane, thereby keeping the cell membrane fully intact. The BCM features high
      precision 3-DOF translational and 2-DOF rotational motion, and a second z-axis
      allowing top-down placement of a micropipette tip onto the cell membrane for SCE.
      As a technical demonstration, the autonomous visual servoing and microinjection
      capabilities of the single-cell manipulator are experimentally shown using sea
      urchin eggs.

PMID- 19605308
TI  - Effects of dielectric parameters of human body on radiation characteristics of
      ingestible wireless device at operating frequency of 430 MHz.
AB  - In order to assess the sensitivities of the radiation characteristics and the
      compliance of ingestible wireless device (IWD) in human body due to the
      uncertainty and intersubject variability of dielectric properties of human body
      tissues, the specific absorption rate (SAR) and radiation characteristics of the
      IWD in two realistic human body models with changed and unchanged dielectric
      values are quantitatively compared using the finite-difference time-domain
      method. Simulations are carried out in 13 scenarios where the IWD is placed in
      the center positions of abdomens in the two body models at the operating
      frequency of 430 MHz with three orientations. Results show that the variation of
      radiation intensity near the surface of abdomen is around 2.5 dB within 20%
      variation of dielectric values. The maximum SAR values increase with the increase
      in conductivities of human body tissues and decrease with the increase in
      relative permittivities of human body tissues. A variation of up to 20% in
      conductivities and relative permittivities, alone or simultaneously, always
      causes a variation of SAR to be less than 10%. As far as the compliance of safety
      is concerned, the maxima of 1-g-averaged and 10-g-averaged SARs can reach 3.16
      and 0.89 W/kg at the input power of 25 mW.

PMID- 19605309
TI  - Characterization of catheter dynamics during percutaneous transluminal catheter
      procedures.
AB  - Remote catheter navigation systems are being developed to reduce the occupational
      risk of the intervening physician. Despite the success of such systems,
      development has occurred with little fundamental knowledge of the catheter
      dynamics applied by the interventionalist. This paper characterizes the
      kinematics of a catheter during manipulation, the minimum applied force/torque
      during interventional procedures, and the maximum force/torque applied by an
      operator to overcome vasculature friction. Ten operators manipulated a 6F
      catheter inside a specialized catheter movement sensor to determine the
      velocities and accelerations of catheter motion. A mass-spring apparatus was
      constructed to measure the forces and torques required to overcome introducer
      sheath and vasculature friction. Results showed the catheter was manipulated at
      peak velocities and accelerations of (mu +/- sigma): 360 +/-180 mm x s(-1) and
      22200 +/-14000 mm x s(- 2), and 19 +/-7 rad x s(- 1) and 900 +/-510 rad x s(- 2),
      for axial and radial directions of motion, respectively. A minimum force of 0.29
      +/- 0.06 N and a torque of 1.15 +/-0.3 mN x m was required to move the catheter
      through the introducer sheath; while the observed maximum applied torque was 15
      mN x m to overcome vasculature friction. The implications of these results for
      future design optimization of an intuitive remote catheter navigation system are
      considered.

PMID- 19605310
TI  - A minimally invasive microdevice for molecular sampling and analysis.
AB  - In this paper, we present a new minimally invasive biopsy microdevice adapted to
      proteomic mass spectrometry analysis. The concept is born from a
      multidisciplinary collaboration in fields of proteomics, cancer research, and
      microtechnology. In mixing different skills, we have developed and manufactured a
      miniaturized biopsy device using microtechnology techniques in order to minimize
      tissue damage during surgical gesture. Dedicated chemically functionalized areas
      were added to the device in order to increase capture yield and specificity
      during tissue contact. Fields of application range from cancer research to the
      study of neurodegenerative diseases.

PMID- 19605311
TI  - A targeting method based on acoustic backscatter for treatment planning in tissue
      ablation using focused ultrasound.
AB  - High-intensity focused ultrasound (HIFU) is a therapeutic modality that can
      produce coagulative necrosis in biological tissue, noninvasively. This technique
      requires the determination of the focus of a HIFU transducer before treatment. We
      investigated a method to localize the focus based on the change in radio
      frequency (RF) signal at HIFU intensity levels below the threshold for tissue
      damage. 2-D RF data were collected during the HIFU exposure at subablative
      intensity levels in ex vivo chicken tissue. The HIFU intensity was then increased
      to induce necrotic lesions in tissue, visualized as hyperecho in B-mode images,
      and the location of hyperecho was used to represent physical lesions, as
      established in our prior studies. Results showed that focal RF amplitude
      increased immediately after HIFU started at subablative intensity. The focus was
      clearly visualized in a 2-D map of the average rate of change (ARC) of RF
      amplitude. The 2-D difference between focus locations based on RF data and
      hyperecho was 1.92 +/- 1.02 mm (mean +/- standard deviation), with no
      statistically significant difference (axial: p = 0.50, lateral: p = 0.07, paired
      t -test). Histological analysis was also performed to examine structural change
      in tissue after HIFU exposure. The results indicated that ARC map could be used
      to determine the focus of a HIFU transducer at subablative intensity, and it has
      the potential to be used for HIFU treatment targeting.

PMID- 19605312
TI  - Characterization of EMG patterns from proximal arm muscles during object- and
      orientation-specific grasps.
AB  - Reach-to-grasp tasks are composed of several actions that are more and more
      considered as simultaneously controlled by the central nervous system in a
      feedforward manner (at least for well-known activities). If this hypothesis is
      correct, during prehension tasks, the activity of proximal muscles (and not only
      of the distal ones used to control finger movements) is modulated according to
      the kind of object to be grasped and its position. This means that different
      objects could be identified by processing the electromyographic (EMG) signals
      recorded from proximal muscles. In this paper, specific experiments have been
      carried out to support this hypothesis in able-bodied subjects. The results
      achieved seem to confirm this possibility by showing that the activation of
      proximal muscles can be statistically different for different grip types. This
      finding supports the hypothesis that proximal and distal muscles are
      simultaneously controlled during reaching and grasping. Moreover, this kind of
      information could allow the development of an EMG-based control strategy based on
      the natural muscular activities selected by the central nervous system.

PMID- 19605313
TI  - Multiple types of movement-related information encoded in hindlimb/trunk cortex
      in rats and potentially available for brain-machine interface controls.
AB  - Brain-machine interface (BMI) systems hold the potential to return lost functions
      to patients with motor disorders. To date, most efforts in BMI have concentrated
      on decoding neural activity from forearm areas of cortex to operate a robotic arm
      or perform other manipulation tasks. Efforts have neglected the locomotion
      functions of hindlimb/trunk cortex. However, the role of cortex in hindlimb
      locomotion of intact rats, which are often model systems for BMI testing, is
      usually considered to be small. Thus, the quality of representations of
      locomotion available in this area was uncertain. We designed a new rodent BMI
      system, and tested decoding of the kinematics of trunk and hindlimbs during
      locomotion using linear regression. Recordings were made from the motor cortex of
      the hindlimb/trunk area in rats using arrays of six tetrodes (24 channels total).
      We found that multiple movement-related variables could be decoded simultaneously
      during locomotion, ranging from the proximal robot/pelvis attachment point, and
      the distal toe position, through hindlimb joint angles and limb endpoint in a
      polar coordinate system. Remarkably, the best reconstructed motion parameters
      were the more proximal kinematics, which might relate to global task variables.
      The pelvis motion was significantly better reconstructed than any other motion
      features.

PMID- 19605314
TI  - A new discriminative common spatial pattern method for motor imagery brain
      computer interfaces.
AB  - Event-related desynchronization/synchronization patterns during right/left motor
      imagery (MI) are effective features for an electroencephalogram-based brain
      computer interface (BCI). As MI tasks are subject-specific, selection of subject
      specific discriminative frequency components play a vital role in distinguishing
      these patterns. This paper proposes a new discriminative filter bank (FB) common
      spatial pattern algorithm to extract subject-specific FB for MI classification.
      The proposed method enhances the classification accuracy in BCI competition III
      dataset IVa and competition IV dataset IIb. Compared to the performance offered
      by the existing FB-based method, the proposed algorithm offers error rate
      reductions of 17.42% and 8.9% for BCI competition datasets III and IV,
      respectively.

PMID- 19605315
TI  - Non-invasive Wet Electrocochleography.
AB  - To detect electrocochleographic (ECochG) potentials generated by the cochlea in
      response to auditory stimuli, either transtympanic or tympanic/extratympanic
      electrodes are currently used. The first are invasive, while the second are
      arranged in contact or very close to the tympanic membrane (TM). To avoid the
      discomfort and the risks inherent to the application of such conventional
      electrodes, this Letter presents an alternative technique. A conducting liquid is
      inserted into the ear canal to act as a distributed electrical interface between
      the TM and an external electrode. Thus, ECochG potentials are detected without
      any direct contact between the solid electrode and the sensitive TM. This
      technique was tested on ten volunteers with single-click auditory stimuli.
      Results showed its efficacy to noninvasively detect useful ECochG responses, with
      accurate morphology and significant amplitude. The technique is comfortable,
      sedation/anesthesia-free, inherently safe, and easy to perform. It also favors
      improvements of contact stability, reductions of contact impedance, and relative
      tolerance to misplacements. As a contraindication, the liquid prevents use on
      subjects affected by tympanic perforation. All these features encourage further
      investigations on this technique as a possible additional tool for the ECochG
      practice.

PMID- 19605316
TI  - Early cortical connective network relating to audiovisual stimulation by partial
      directed coherence analysis.
AB  - Cross-modal sensory integration between the auditory and visual systems has long
      been a topic of interest in cognitive neuroscience, but spatiotemporal cortical
      interdependence under audiovisual stimulation is still poorly understood. In this
      letter, parametric spectral analysis, specifically partial directed coherence
      (PDC), is used to study the cortical connective causal-interdependence network
      under audiovisual cognitive processes within the time window of the N1 component,
      i.e., 96--145 ms poststimulus in the event-related potential (ERP). A total of 13
      subjects (age: 22.9+/-0.8 years; male/female = 9/4) performed an audiovisual
      recognition task. Multichannel EEG signals were analyzed using an adaptive
      multivariate autoregressive model to identify causal influences between different
      cortical areas. Three different cortical connective networks were detected, and
      by comparing the cortical PDC network in the early cognitive process of
      audiovisual (VA) perception with that in unimodal situations (V or A), it was
      found that the left temporal cortex (TC) might be responsible for audiovisual
      integration. Such electrophysiological findings were highly consistent with
      previous functional neuroimaging results. Moreover, the results presented here
      show the dynamics of lateral causal influences during audiovisual integration.

PMID- 19605317
TI  - Stimulatory current at the edge of an inactive conductor in an electric field:
      role of nonlinear interfacial current-voltage relationship.
AB  - Cardiac electric field stimulation is critical for the mechanism of
      defibrillation. The presence of certain inactive epicardial conductors in the
      field during defibrillation can decrease the defibrillation threshold. We
      hypothesized this decrease is due to stimulatory effects of current across the
      interface between the inactive conductor and the heart during field stimulation.
      To examine this current and its possible stimulatory effects, we imaged
      transmittance of indium-tin-oxide (ITO) conductors, tested for indium with X-ray
      diffraction, created a computer model containing realistic ITO interfacial
      properties, and optically mapped excitation of rabbit heart during electric field
      stimulation in the presence of an ITO conductor. Reduction of indium decreased
      transmittance at the edge facing the anodal shock electrode when trans
      interfacial voltage exceeded standard reduction potential. The interfacial
      current-voltage relationship was nonlinear, producing larger conductances at
      higher currents. This nonlinearity concentrated the interfacial current near
      edges in images and in a computer model. The edge current was stimulatory,
      producing early postshock excitation of rabbit ventricles. Thus, darkening of ITO
      indicates interfacial current by indium reduction. Interfacial nonlinearity
      concentrates current near the edge where it can excite the heart. Stimulatory
      current at edges may account for the reported decrease in defibrillation
      threshold by inactive conductors.

PMID- 19605318
TI  - Denoising of dynamic contrast-enhanced MR images using dynamic nonlocal means.
AB  - This paper presents a new algorithm for denoising dynamic contrast-enhanced (DCE)
      MR images. It is a novel variation on the nonlocal means (NLM) algorithm. The
      algorithm, called dynamic nonlocal means (DNLM), exploits the redundancy of
      information in the temporal sequence of images. Empirical evaluations of the
      performance of the DNLM algorithm relative to seven other denoising methods
      simple Gaussian filtering, the original NLM algorithm, a trivial extension of NLM
      to include the temporal dimension, bilateral filtering, anisotropic diffusion
      filtering, wavelet adaptive multiscale products threshold, and traditional
      wavelet thresholding-are presented. The evaluations include quantitative
      evaluations using simulated data and real data (20 DCE-MRI data sets from routine
      clinical breast MRI examinations) as well as qualitative evaluations using the
      same real data (24 observers: 14 image/signal-processing specialists, 10 clinical
      breast MRI radiographers). The results of the quantitative evaluation using the
      simulated data show that the DNLM algorithm consistently yields the smallest MSE
      between the denoised image and its corresponding original noiseless version. The
      results of the quantitative evaluation using the real data provide evidence, at
      the alpha = 0.05 level of significance, that the DNLM algorithm yields the
      smallest MSE between the denoised image and its corresponding original noiseless
      version. The results of the qualitative evaluation provide evidence, at the alpha
      = 0.05 level of significance, that the DNLM algorithm performs visually better
      than all of the other algorithms. Collectively the qualitative and quantitative
      results suggest that the DNLM algorithm more effectively attenuates noise in DCE
      MR images than any of the other algorithms.

PMID- 19605319
TI  - Correction for susceptibility-induced distortion in echo-planar imaging using
      field maps and model-based point spread function.
AB  - Susceptibility-induced distortion is one of the major artifacts in echo-planar
      imaging (EPI), and many solutions have been proposed for the problem, including
      the Fourier method and the point spread function (PSF) method. In this paper, a
      framework unifying both methods is presented. Under this framework, a model-based
      PSF method is proposed in which the PSF of the source object is modeled along
      with a single field map measured by TE-offset reference scans. EPI images of a
      phantom and a healthy human subject were acquired, and the results of distortion
      correction by the Fourier method, linear interpolation method, and the model
      based PSF method were compared. The results showed that the model-based PSF
      method could correct for geometric distortion and signal intensity distortion
      satisfactorily, avoiding the rippling artifact shown in the Fourier method. In
      conclusion, the proposed framework gave us an overall picture of how different
      correction methods work. The model-based PSF method, which required fewer
      reference scans and less computational load, was more clinically feasible than
      other methods.

PMID- 19605320
TI  - Image guided personalization of reaction-diffusion type tumor growth models using
      modified anisotropic eikonal equations.
AB  - Reaction-diffusion based tumor growth models have been widely used in the
      literature for modeling the growth of brain gliomas. Lately, recent models have
      started integrating medical images in their formulation. Including different
      tissue types, geometry of the brain and the directions of white matter fiber
      tracts improved the spatial accuracy of reaction-diffusion models. The adaptation
      of the general model to the specific patient cases on the other hand has not been
      studied thoroughly yet. In this paper, we address this adaptation. We propose a
      parameter estimation method for reaction-diffusion tumor growth models using time
      series of medical images. This method estimates the patient specific parameters
      of the model using the images of the patient taken at successive time instances.
      The proposed method formulates the evolution of the tumor delineation visible in
      the images based on the reaction-diffusion dynamics; therefore, it remains
      consistent with the information available. We perform thorough analysis of the
      method using synthetic tumors and show important couplings between parameters of
      the reaction-diffusion model. We show that several parameters can be uniquely
      identified in the case of fixing one parameter, namely the proliferation rate of
      tumor cells. Moreover, regardless of the value the proliferation rate is fixed
      to, the speed of growth of the tumor can be estimated in terms of the model
      parameters with accuracy. We also show that using the model-based speed, we can
      simulate the evolution of the tumor for the specific patient case. Finally, we
      apply our method to two real cases and show promising preliminary results.

PMID- 19605322
TI  - Stability analysis of discrete-time recurrent neural networks with stochastic
      delay.
AB  - This paper is concerned with the stability analysis of discrete-time recurrent
      neural networks (RNNs) with time delays as random variables drawn from some
      probability distribution. By introducing the variation probability of the time
      delay, a common delayed discrete-time RNN system is transformed into one with
      stochastic parameters. Improved conditions for the mean square stability of these
      systems are obtained by employing new Lyapunov functions and novel techniques are
      used to achieve delay dependence. The merit of the proposed conditions lies in
      its reduced conservatism, which is made possible by considering not only the
      range of the time delays, but also the variation probability distribution. A
      numerical example is provided to show the advantages of the proposed conditions.

PMID- 19605321
TI  - Prostate brachytherapy seed reconstruction with Gaussian blurring and optimal
      coverage cost.
AB  - Intraoperative dosimetry in prostate brachytherapy requires localization of the
      implanted radioactive seeds. A tomosynthesis-based seed reconstruction method is
      proposed. A three-dimensional volume is reconstructed from Gaussian-blurred
      projection images and candidate seed locations are computed from the
      reconstructed volume. A false positive seed removal process, formulated as an
      optimal coverage problem, iteratively removes "ghost" seeds that are created by
      tomosynthesis reconstruction. In an effort to minimize pose errors that are
      common in conventional C-arms, initial pose parameter estimates are iteratively
      corrected by using the detected candidate seeds as fiducials, which automatically
      "focuses" the collected images and improves successive reconstructed volumes.
      Simulation results imply that the implanted seed locations can be estimated with
      a detection rate of > or = 97.9% and > or = 99.3% from three and four images,
      respectively, when the C-arm is calibrated and the pose of the C-arm is known.
      The algorithm was also validated on phantom data sets successfully localizing the
      implanted seeds from four or five images. In a Phase-1 clinical trial, we were
      able to localize the implanted seeds from five intraoperative fluoroscopy images
      with 98.8% (STD=1.6) overall detection rate.

PMID- 19605323
TI  - Segmented-memory recurrent neural networks.
AB  - Conventional recurrent neural networks (RNNs) have difficulties in learning long
      term dependencies. To tackle this problem, we propose an architecture called
      segmented-memory recurrent neural network (SMRNN). A symbolic sequence is broken
      into segments and then presented as inputs to the SMRNN one symbol per cycle. The
      SMRNN uses separate internal states to store symbol-level context, as well as
      segment-level context. The symbol-level context is updated for each symbol
      presented for input. The segment-level context is updated after each segment. The
      SMRNN is trained using an extended real-time recurrent learning algorithm. We
      test the performance of SMRNN on the information latching problem, the "two
      sequence problem" and the problem of protein secondary structure (PSS)
      prediction. Our implementation results indicate that SMRNN performs better on
      long-term dependency problems than conventional RNNs. Besides, we also
      theoretically analyze how the segmented memory of SMRNN helps learning long-term
      temporal dependencies and study the impact of the segment length.

PMID- 19605324
TI  - Rapid image completion system using multiresolution patch-based directional and
      nondirectional approaches.
AB  - This study presents a rapid image completion system comprising a training (or
      analysis) process and an image completion (or synthesis) process. The proposed
      system adopts a multiresolution approach, which not only improves the convergence
      rate of the synthesis process, but also provides the ability to deal with large
      replaced regions. In the training process, a down-sampling approach is applied to
      create a patch-based texture eigenspace based on multiresolution background
      region information. In the image completion process, an up-sampling approach is
      applied to synthesize the replaced foreground regions. To ensure the continuity
      of the geometric texture structure between the original background scene regions
      and the replaced foreground regions, directional and nondirectional image
      completion approaches are developed to reconstruct the global geometric structure
      and to enhance the local detailed features of the replaced foreground regions in
      the lower and higher resolution level images, respectively. Moreover, the
      synthesis priority order of the individual patches and the appropriate choice of
      completion scheme (i.e., directional or nondirectional) are both determined in
      accordance with a Hessian matrix decision value (HMDV) parameter. Finally, a
      texture refinement process is performed to optimize the resolution of the
      synthesized result.

PMID- 19605325
TI  - Multiresolution monogenic signal analysis using the Riesz-Laplace wavelet
      transform.
AB  - The monogenic signal is the natural 2-D counterpart of the 1-D analytic signal.
      We propose to transpose the concept to the wavelet domain by considering a
      complexified version of the Riesz transform which has the remarkable property of
      mapping a real-valued (primary) wavelet basis of L(2) (R(2)) into a complex one.
      The Riesz operator is also steerable in the sense that it give access to the
      Hilbert transform of the signal along any orientation. Having set those
      foundations, we specify a primary polyharmonic spline wavelet basis of L(2)
      (R(2)) that involves a single Mexican-hat-like mother wavelet (Laplacian of a B
      spline). The important point is that our primary wavelets are quasi-isotropic:
      they behave like multiscale versions of the fractional Laplace operator from
      which they are derived, which ensures steerability. We propose to pair these real
      valued basis functions with their complex Riesz counterparts to specify a
      multiresolution monogenic signal analysis. This yields a representation where
      each wavelet index is associated with a local orientation, an amplitude and a
      phase. We give a corresponding wavelet-domain method for estimating the
      underlying instantaneous frequency. We also provide a mechanism for improving the
      shift and rotation-invariance of the wavelet decomposition and show how to
      implement the transform efficiently using perfect-reconstruction filterbanks. We
      illustrate the specific feature-extraction capabilities of the representation and
      present novel examples of wavelet-domain processing; in particular, a robust,
      tensor-based analysis of directional image patterns, the demodulation of
      interferograms, and the reconstruction of digital holograms.

PMID- 19605326
TI  - An iterative data mining approach for mining overlapping coexpression patterns in
      noisy gene expression data.
AB  - Clustering is concerned with the discovery of groupings of records in a database.
      Many clustering problems are defined as partitioning problems in the sense that
      the similar records are grouped into nonoverlapping partitions. However, the
      clustering of gene expression data to discover coexpressed genes may not always
      be meaningful if this problem is reduced into a partitioning problem. Due to the
      complexity of the underlying biological processes, a protein can interact with
      one or more other proteins belonging to different functional classes in order to
      perform a particular biological role. For this reason, when responding to
      different external stimulants, a gene that produces a particular protein can
      coexpress with more than one group of other genes. The gene can therefore belong
      to more than one group of coexpressed genes. This poses a challenge to many
      clustering algorithms as they are not originally developed to discover
      overlapping clusters in noisy gene expression data. In this paper, we propose an
      iterative data mining approach that consists of two phases as follows. In phase
      1, a clustering algorithm is used to discover the initial, nonoverlapping
      partitioning of gene expression profiles in gene expression data. Then, the
      partition memberships of genes are redetermined iteratively in phase 2 by a
      pattern discovery technique so as to determine that if a gene should remain in
      the same partition, be moved to another partition, or be also grouped together
      with other genes in another partitions. The proposed approach has been tested
      with both artificial and real datasets. Experimental results show that it can
      improve the performances of existing clustering algorithms and is able to
      effectively discover overlapping clusters in noisy gene expression data.

PMID- 19605327
TI  - Effectiveness of behavioral parent therapy in preschool children with attention
      deficit hyperactivity disorder.
AB  - The purpose of this study was to assess the effectiveness of a behavioral parent
      therapy (BPT) program in children with attention-deficit hyperactivity disorder
      (ADHD) using multidimensional evaluations, the Child Behavior Checklist (CBCL)
      and the Teacher Report Form (TRF). Between 2001 and 2005, the parents of 21
      preschool children with ADHD were divided into six groups and participated in a
      series of 11 BPT sessions. Before and after BPT, the parents completed the CBCL,
      and the teachers completed the TRF. The behavioral and emotional problems of the
      children showed improvement after the BPT sessions, specifically for the
      following categories: internalizing problems, anxious/depressed syndromes,
      somatic complaints, externalizing problems, rule-breaking behaviors, aggressive
      behaviors, social problems, thought problems, and attention problems. In the DSM
      oriented scale of the CBCL, affective problems, anxiety problems, somatic
      problems, ADHD problems, oppositional defiant disorder problems, and conduct
      disorder problems showed significant improvements. On the DSM scale of the TRF,
      Inattention syndrome improved significantly after the BPT sessions, while other
      syndromes showed non-significant changes. We conclude that the BPT program
      significantly improved the childrens behavioral problems at home and inattention
      problems at school.

PMID- 19605328
TI  - Determinants of peripheral arterial stiffness in patients with chronic kidney
      disease in southern Taiwan.
AB  - High prevalences of peripheral artery occlusive disease (PAOD) and increased
      arterial stiffness have been reported in patients with chronic kidney disease
      (CKD). However, these have not been assessed in Taiwan where the prevalence of
      CKD is high. The aim of this study was to investigate the determinants of PAOD
      and arterial stiffness in patients with CKD in southern Taiwan. We enrolled 169
      patients with stage 3-5 CKD in one regional hospital. Ankle-brachial index (ABI)
      and brachial-ankle pulse wave velocity were measured using an ABI-form device
      (Colin VP1000). In multivariate analysis, ABI<0.9 was positively correlated with
      the presence of diabetes mellitus (p=0.014) and negatively correlated with the
      estimated glomerular filtration rate (eGFR) (p=0.049), and increased brachial
      ankle pulse wave velocity was correlated with increased age, diabetes mellitus,
      increased systolic blood pressure, decreased pulse pressure and decreased eGFR.
      This study identified determinants of PAOD and arterial stiffness in patients
      with CKD in one hospital in southern Taiwan. In addition to the traditional
      atherosclerotic risk factors, decreased eGFR was also correlated with PAOD and
      increased arterial stiffness in these patients.

PMID- 19605330
TI  - Resveratrol protects against ultraviolet A-mediated inhibition of the phagocytic
      function of human retinal pigment epithelial cells via large-conductance calcium
      activated potassium channels.
AB  - This study was undertaken to examine the protective effect of resveratrol on
      human retinal pigment epithelial (RPE) cell phagocytosis against ultraviolet
      irradiation damage. Cultured RPE cells were exposed to ultraviolet A (UVA, 20
      minutes) irradiation, and treated with meclofenamic acid (30 microM, 20 minutes),
      paxilline (100 nM, 20 minutes) or resveratrol (10 microM, 20 minutes).
      Meclofenamic acid and resveratrol were given after exposure to UVA. Pretreatment
      with meclofenamic acid, resveratrol or paxilline before UVA irradiation was also
      performed. Fluorescent latex beads were then fed for 4 hours and the phagocytotic
      function was assessed by flow cytometry. UVA irradiation inhibited the phagocytic
      function of human RPE cells. The large-conductance calcium-activated potassium
      channel activator meclofenamic acid ameliorated the damage caused by UVA
      irradiation. Pretreatment with resveratrol acid also provided protection against
      damage caused by UVA. Posttreatment with meclofenamic acid offered mild
      protection, whereas resveratrol did not. In conclusion, the red wine flavonoid
      resveratrol ameliorated UVA-mediated inhibition of human RPE phagocytosis. The
      underlying mechanism might involve the large-conductance calcium-activated
      potassium channels.

PMID- 19605331
TI  - Aberrant expression of CD19 and CD43 in a patient with therapy-related acute
      myeloid leukemia and a history of mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with frequent
      involvement of the gastrointestinal tract and peripheral blood (PB). In addition
      to the B cell markers, the neoplastic cells express CD5 and CD43. In patients
      with a prior history of MCL with PB involvement, the appearance of leukemic cells
      after chemotherapy usually heralds a relapse, particularly if the leukemic cells
      express B cell markers and CD43. We report a patient with MCL who presented with
      multiple lymphomatous polyposis of the intestine. The staging procedures revealed
      the involvement of lymph nodes, bone marrow and PB. Three years after
      chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the
      PB was noted. Leukemic cells obtained from bone marrow aspirate expressed CD19
      and CD43, suggesting a relapse. Detailed cytomorphological and immunophenotypic
      studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of
      therapy-related acute myeloid leukemia was made. This case illustrates the
      importance of morphologic examination and performing a complete antibody panel in
      the diagnosis of a suspected relapse in patients with a prior history of
      lymphoma.

PMID- 19605329
TI  - Vardenafil reduces testicular damage following ischemia/reperfusion injury in
      rats.
AB  - We investigated the effect of intraperitoneal vardenafil (1 mg/kg) administration
      during an ischemic period in a rat model of testicular torsion/detorsion (T/D).
      Twenty-one adult Wistar rats were equally randomized into a control group, a T/D
      group and a vardenafil group. The control group was designed to collect basal
      values for biochemical and histopathological parameters. The T/D group underwent
      testicular torsion for 1 hour. The vardenafil group received vardenafil (1 mg/kg)
      intraperitoneally at 30 minutes after torsion. All rats were sacrificed 4 hours
      after reperfusion to evaluate the tissue levels of malondialdehyde and total
      antioxidant status. Germ cell apoptosis was evaluated using the apoptosis
      protease activating factor 1 antibody in all groups. The expressions of
      endothelial nitric oxide synthase (NOS) and inducible NOS were also assessed in
      both testes of all rats. The malondialdehyde levels in the T/D group were
      significantly higher than in the control and vardenafil groups. There were also
      significant decreases in total antioxidant status in the T/D group compared with
      the control and vardenafil groups. Vardenafil treatment significantly reduced
      apoptosis protease activating factor 1, endothelial NOS and inducible NOS levels
      in the vardenafil group compared with the T/D group. Administration of 1 mg/kg
      vardenafil during testicular torsion decreased ischemia/reperfusion cellular
      damage. Our results indicate that the reduction in oxidative stress by vardenafil
      may play a major role in its cytoprotective effects.

PMID- 19605333
TI  - Eccrine porocarcinoma of the auricle: a case report.
AB  - Eccrine porocarcinoma (EP) is a rare skin malignant lesion representing 0.005
      0.01% of all cutaneous tumors. It is a tumor that most commonly present in
      elderly people aged over 60 years. Approximately 250 cases of EP have been
      reported since this disease was first described in 1963. However, only three
      cases occurring specifically on the ear (including the current case) have been
      documented in the literature to date. Based on the rarity of EP of the ear, we
      present this 78-year-old man with EP on the right ear lobule, which was diagnosed
      accidentally during the management of other unrelated problems. The etiology,
      diagnosis, treatment and prognosis of this disease are discussed, with a brief
      review of the literature in this report.

PMID- 19605332
TI  - Isolated pancreatic metastasis of a malignant pleural mesothelioma.
AB  - Metastatic malignant mesothelioma of the pleura is uncommon at the time of
      initial diagnosis. When metastases are present, the major sites always include
      regional lymph nodes, the contralateral lung, liver, adrenal glands and kidneys.
      Here, we describe an extremely rare case of isolated pancreatic metastasis of
      mesothelioma of the pleura in a 40-year-old man who initially presented with
      epigastric discomfort and hunger pain, which were refractory to medical
      treatments. The possibility of pancreatic metastatic lesion should be considered
      in patients with malignant pleural mesothelioma in the presence of refractory
      epigastric tenderness.

PMID- 19605334
TI  - Schwannomatosis of a single intercostal nerve: a case report.
AB  - Schwannomatosis is a rare form of neurofibromatosis and is characterized by more
      than one schwannoma without any sign of neurofibromatosis. We report a case of a
      60-year-old male patient admitted with progressive chest discomfort who was found
      to have six encapsulated tumors along the seventh intercostal space with a
      maximum tumor size of 3x2x1 cm.

PMID- 19605335
TI  - Comparison of clinical application of the Abbott HBV PCR kit and the VERSANT HBV
      DNA 3.0 test to measure serum hepatitis B virus DNA in Taiwanese patients.
AB  - With an estimated 350-400 million people worldwide chronically infected with
      hepatitis B virus (HBV), and the subsequent serious complications caused by liver
      damage including cirrhosis, liver failure, and hepatocellular carcinoma, HBV
      infection remains a global health issue, particularly in Taiwan, an HBV
      hyperendemic area. Sensitive and accurate quantification of HBV DNA is necessary
      to monitor patients with chronic hepatitis B who are receiving antiviral therapy
      to determine treatment response and adapt therapy. We evaluated and compared the
      clinical performance of two HBV DNA assays based on different technologies: the
      RealArt HBV PCR Kit (Abbott HBV DNA PCR kit, real-time polymerase chain reaction
      assay, detection limit: 27 IU/mL) and the VERSANT bDNA 3.0 assay (Bayer, branched
      DNA signal amplification assay, detection limit: 357 IU/mL). Serum levels of HBV
      DNA in 173 chronic HBV carriers were determined using both the RealArt HBV PCR
      Kit and the VERSANT bDNA 3.0 test. Of the 173 samples analyzed for baseline viral
      load detection, HBV DNA was quantifiable in 147 patients (82.1%) by the RealArt
      HBV PCR Kit, which was significantly higher than the 92 (53.2%) samples
      quantified by the VERSANT bDNA 3.0 assay. A total of 86 (49.7%) samples were
      quantifiable by both assays, whereas 25 (14.5%) were below the detection limit of
      both assays. The HBV DNA quantification values measured by the RealArt HBV PCR
      Kit and the VERSANT bDNA 3.0 assay were positively correlated (Spearman's rank
      correlation coefficient r = 0.932, p < 0.001). On average, the results derived
      from the RealArt HBV PCR Kit were 0.67 log lower than those of the VERSANT bDNA
      3.0 assay. HBV DNA concentrations were significantly higher in 63 HBV e antigen
      (HBeAg)-seropositive patients than in 110 HBeAg-seronegative patients (5.42 +/-
      2.34 logs vs. 3.21 +/- 2.27 logs, p < 0.001). The RealArt HBV PCR Kit is more
      sensitive and has a wider dynamic range than the VERSANT bDNA 3.0 assay in the
      clinical setting of chronic hepatitis B patients. The sensitivity and wide
      dynamic range of the PCR assay allow optimal monitoring and timely adaptation of
      antiviral therapy. Nevertheless, the HBV DNA values measured by the RealArt HBV
      PCR Kit and the VERSANT bDNA 3.0 assay were significantly correlated.

PMID- 19605336
TI  - Comparison of plasma antioxidant levels and related metabolic parameters between
      smokers and non-smokers.
AB  - The relationship between cigarette smoking and cell damage is complicated,
      particularly considering the role of oxidative stress. The aim of this study was
      to identify the relationships among plasma nicotine metabolites, lipophilic
      antioxidants, and metabolic parameters in smokers and nonsmokers. This cross
      sectional study recruited 100 subjects who visited the Department of Family
      Medicine at Kaohsiung Medical University Hospital. Excluding 14 ineligible cases,
      46 smokers and 40 non-smokers were enrolled. Plasma nicotine metabolites,
      lipophilic antioxidants (including retinol, lycopene, alpha-carotene, beta
      carotene, delta-tocopherol, gamma-tocopherol and alpha-tocopherol), related
      metabolic parameters, and body composition (including height, weight, body mass
      index, body fat, and waist circumference) were examined by comparison of means,
      correlations and regressions. Significant correlations among nicotine
      metabolites, age, sex, body composition and plasma lipophilic antioxidants were
      noted. Nicotine metabolites, age, body height and body weight were closely
      associated with plasma antioxidant levels (p < 0.05) in multiple linear
      regression. The levels of alpha-carotene, beta-carotene, gamma-tocopherol and
      lycopene were lower in smokers than in non-smokers (p < 0.01). The plasma level
      of high-sensitivity C-reactive protein (hsCRP), which is a marker for high
      cardiovascular risk, was higher in smokers than in non-smokers (p = 0.003). We
      conclude that the lower plasma antioxidant levels and the higher level of hsCRP
      in smokers may lead to decreased protective efficacy compared with non-smokers.
      Further studies are warranted to support our hypothesis.

PMID- 19605337
TI  - Minimally invasive distal metatarsal osteotomy for mild-to-moderate hallux valgus
      deformity.
AB  - Minimally invasive surgery has recently been introduced for foot and ankle
      surgery, and hallux valgus surgery is no exception. The purpose of our study was
      to analyze the early results and to present our experience of minimally invasive
      distal metatarsal osteotomy in correcting mild-to-moderate hallux valgus
      deformities. Between September 2005 and December 2006, 31 consecutive patients
      (47 feet) with mild-to-moderate hallux valgus deformities underwent minimally
      invasive distal metatarsal osteotomies. The clinical and radiographic outcomes
      were assessed. The satisfaction rate was 90.32%. The mean total American
      Orthopedic Foot and Ankle Society hallux-metatarsophalangeal-interphalangeal
      scale was 92.7 points. Complications included two (4.26%) episodes of stiffness,
      six (12.77%) episodes of pin tract infection, and one (2.13%) deep infection.
      There were no cases with nonunion, malunion, overcorrection, transfer
      metatarsalgia or osteonecrosis. On weight-bearing anteroposterior foot
      radiographs, the mean hallux valgus angle and first intermetatarsal angle
      corrections were 11.8 degrees and 6.3 degrees, respectively, which is a
      statistically significant difference (p < 0.001) between the preoperative and
      postoperative status. Here, minimally invasive distal metatarsal osteotomy was
      associated with good satisfaction, functional improvement and low complication
      rates. This technique offers an effective, safe and simple way to treat hallux
      valgus with a first intermetatarsal angle less than 15 degrees.

PMID- 19605338
TI  - Comparison of laparoscopic adrenalectomy with open surgery for adrenal tumors.
AB  - The role of laparoscopy in the management of adrenal tumors is well established.
      However, there are very few head-to-head comparisons between laparoscopic and
      open methods at the same institution. We retrospectively evaluated the operative
      and postoperative parameters of laparoscopic adrenalectomy for adrenal tumors and
      compared the results with those of traditional open adrenalectomy. Eighty-eight
      patients with adrenal tumors underwent adrenalectomy between January 1997 and
      October 2008 at our institute. Clinical data were retrospectively collected after
      assigning the patients into Group I (n = 51), who underwent the laparoscopic
      method, and Group II (n = 37), who underwent the traditional open method, by
      reviewing the patients' charts and related data. Patients in Group I experienced
      significantly less blood loss (88.6 +/- 93.0 mL vs. 321.4 +/- 265.4 mL, p <
      0.01), shorter hospital stay (6.7 +/- 4.3 days vs. 11.3 +/- 5.4 days, p < 0.01)
      and earlier oral intake (1.5 +/- 0.6 days vs. 2.2 +/- 0.8 days, p < 0.01)
      postoperatively. In Group I, eight patients had adrenal tumors larger than 6 cm
      and no statistically significant differences were found compared with the other
      patients in Group I. Two patients in Group I had malignancies and no local or
      port site recurrence was found at regular follow-up. There was no mortality in
      either group. Laparoscopic adrenalectomy is a safe, effective and minimally
      invasive approach with the advantages of better cosmesis, less blood loss,
      shorter hospital stay and more rapid recovery. We recommend that laparoscopic
      adrenalectomy is considered as the gold standard procedure for adrenal tumors,
      irrespective of whether the tumor is benign or malignant.

PMID- 19605339
TI  - Hemostasis in retropubic radical prostatectomy with Ankaferd BloodStopper: a case
      report.
AB  - Ankaferd BloodStopper (ABS) is a licensed medicinal plant product that provides
      active hemostasis in external, postsurgical and dental bleeding, and is approved
      in Turkey by the Ministry of Health. The use of ABS for internal organ hemorrhage
      is under investigation. Our clinic is one of the certified centers conducting a
      phase II trial investigating the effects and reliability of ABS in urogenital
      surgery. We have used ABS to stop bleeding during radical retropubic
      prostatectomy in one patient, presented here as a case report.

PMID- 19605340
TI  - Intramuscular low-grade fibromyxoid sarcoma: a case report.
AB  - Low-grade fibromyxoid sarcoma (LGFMS) is a rare neoplasm that commonly arises in
      the deep soft tissues of the lower extremities, particularly in the thigh. LGFMS
      occurs preferentially in young male adults. The microscopic appearance of LGFMS
      exhibits bland fibroblastic spindle cells with a whorled or linear arrangement in
      fibrous and myxoid areas. Although LGFMS has a deceptively benign histologic
      appearance, local recurrence and late metastases have frequently been reported.
      Diagnosis of LGFMS is still difficult because of its characteristic bland-looking
      histologic features that can be confused with other benign or low-grade
      fibromyxoid lesions. Although immunohistochemical staining can offer an overview
      of the differential diagnosis of myxoid tumors of soft tissue, it is sometimes
      limited for diagnosis of LGFMS. However, recent cytogenetic and molecular
      analyses have provided significant improvements in the diagnosis of LGFMS. Such
      analyses have demonstrated that most cases of LGFMS have a characteristic
      t(7,16)(q33;p11) translocation, resulting in the FUS-CREB3L2 fusion gene. We
      report a 29-year-old female who presented with a LGFMS located in the soleus
      muscle of her left lower leg. Preoperative imaging suggested the possibility of
      an intramuscular histiocytoma of the left soleus muscle. In conclusion, diagnosis
      of LGFMS can be challenging in routine practice in surgical pathology because of
      its bland-looking features. The immunohistochemical and ultrastructural findings
      were consistent with the fibroblastic properties of LGFMS. Cytogenetic and/or
      molecular genetic analyses can be used as ancillary diagnostic tools for LGFMS.

PMID- 19605341
TI  - Continuous infraclavicular block for forearm amputation after being bitten by a
      saltwater crocodile (Crocodylus porosus): a case report.
AB  - Two important issues after a complete right forearm amputation are replantation
      and ongoing pain management. There are no reports of successful forearm
      replantation as a consequence of a crocodile bite. Here, we discuss our pain
      management in a case of complete forearm amputation after a bite from a saltwater
      crocodile (Crocodylus porosus), which necessitated six further operations to
      achieve successful replantation. Continuous infraclavicular brachial plexus block
      was effective for acute pain control in this case. We strongly recommend
      performing the block with an indwelling catheter under ultrasound guidance for
      higher accuracy and safety.

PMID- 19605342
TI  - Mediastinal hematoma caused by central venous catheterization: a rare cause of
      obscure blood loss.
AB  - Gastrointestinal hemorrhage, internal bleeding beyond the gastrointestinal tract
      and hemolysis are common causes of blood loss in intensive care unit patients.
      However, mediastinal hematoma is a rare cause of blood loss and is not usually
      detected. Here, we report a patient who developed a mediastinal hematoma
      resulting from central venous catheterization who presented with obscure blood
      loss refractory to blood transfusion. A mediastinal hematoma should be considered
      in the presence of obscure blood loss in patients with catheter placement.

PMID- 19605343
TI  - Retinoic acid syndrome in a patient with psoriasis.

PMID- 19605344
TI  - Regulation of Rad51 recombinase presynaptic filament assembly via interactions
      with the Rad52 mediator and the Srs2 anti-recombinase.
AB  - Homologous recombination represents an important means for the error-free
      elimination of DNA double-strand breaks and other deleterious DNA lesions from
      chromosomes. The Rad51 recombinase, a member of the RAD52 group of recombination
      proteins, catalyzes the homologous recombination reaction in the context of a
      helical protein polymer assembled on single-stranded DNA (ssDNA) that is derived
      from the nucleolytic processing of a primary lesion. The assembly of the Rad51
      ssDNA nucleoprotein filament, often referred to as the presynaptic filament, is
      prone to interference by the single-strand DNA-binding factor replication protein
      A (RPA). The Saccharomyces cerevisiae Rad52 protein facilitates presynaptic
      filament assembly by helping to mediate the displacement of RPA from ssDNA. On
      the other hand, disruption of the presynaptic filament by the Srs2 helicase leads
      to a net exchange of Rad51 for RPA. To understand the significance of protein
      protein interactions in the control of Rad52- or Srs2-mediated presynaptic
      filament assembly or disassembly, we have examined two rad51 mutants, rad51 Y388H
      and rad51 G393D, that are simultaneously ablated for Rad52 and Srs2 interactions
      and one, rad51 A320V, that is differentially inactivated for Rad52 binding for
      their biochemical properties and also for functional interactions with Rad52 or
      Srs2. We show that these mutant rad51 proteins are impervious to the mediator
      activity of Rad52 or the disruptive function of Srs2 in concordance with their
      protein interaction defects. Our results thus provide insights into the
      functional significance of the Rad51-Rad52 and Rad51-Srs2 complexes in the
      control of presynaptic filament assembly and disassembly. Moreover, our
      biochemical studies have helped identify A320V as a separation-of-function
      mutation in Rad51 with regards to a differential ablation of Rad52 interaction.

PMID- 19605345
TI  - Characterization of Mycobacterium leprae RecA intein, a LAGLIDADG homing
      endonuclease, reveals a unique mode of DNA binding, helical distortion, and
      cleavage compared with a canonical LAGLIDADG homing endonuclease.
AB  - Mycobacterium leprae, which has undergone reductive evolution leaving behind a
      minimal set of essential genes, has retained intervening sequences in four of its
      genes implicating a vital role for them in the survival of the leprosy bacillus.
      A single in-frame intervening sequence has been found embedded within its recA
      gene. Comparison of the M. leprae recA intervening sequence with the known
      intervening sequences indicated that it has the consensus amino acid sequence
      necessary for being a LAGLIDADG-type homing endonuclease. In light of massive
      gene decay and function loss in the leprosy bacillus, we sought to investigate
      whether its recA intervening sequence encodes a catalytically active homing
      endonuclease. Here we show that the purified M. leprae RecA intein (PI-MleI)
      binds to cognate DNA and displays endonuclease activity in the presence of
      alternative divalent cations, Mg2+ or Mn2+. A combination of approaches,
      including four complementary footprinting assays such as DNase I, copper
      phenanthroline, methylation protection, and KMnO4, enhancement of 2-aminopurine
      fluorescence, and mapping of the cleavage site revealed that PI-MleI binds to
      cognate DNA flanking its insertion site, induces helical distortion at the
      cleavage site, and generates two staggered double strand breaks. Taken together,
      these results implicate that PI-MleI possesses a modular structure with separate
      domains for DNA target recognition and cleavage, each with distinct sequence
      preferences. From a biological standpoint, it is tempting to speculate that our
      findings have implications for understanding the evolution of the LAGLIDADG
      family of homing endonucleases.

PMID- 19605346
TI  - Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae.
AB  - The Mcm10 protein is essential for chromosomal DNA replication in eukaryotic
      cells. We purified the Saccharomyces cerevisiae Mcm10 (ScMcm10) and characterized
      its DNA binding properties. Electrophoretic mobility shift assays and surface
      plasmon resonance analysis showed that ScMcm10 binds stably to both double strand
      (ds) DNA and single strand (ss) DNA. On short DNA templates of 25 or 50 bp,
      surface plasmon resonance analysis showed a approximately 1:1 stoichiometry of
      ScMcm10 to dsDNA. On longer dsDNA templates, however, multiple copies of ScMcm10
      cooperated in the rapid assembly of a large, stable nucleoprotein complex. The
      amount of protein bound was directly proportional to the length of the DNA, with
      an average occupancy spacing of 21-24 bp. This tight spacing is consistent with a
      nucleoprotein structure in which ScMcm10 is aligned along the helical axis of the
      dsDNA. In contrast, the stoichiometry of ScMcm10 bound to ssDNA of 20-50
      nucleotides was approximately 3:1 suggesting that interaction with ssDNA induces
      the assembly of a multisubunit ScMcm10 complex composed of at least three
      subunits. The tight packing of ScMcm10 on dsDNA and the assembly of a
      multisubunit complex on ssDNA suggests that, in addition to protein-DNA, protein
      protein interactions may be involved in forming the nucleoprotein complex. We
      propose that these DNA binding properties have an important role in (i)
      initiation of DNA replication and (ii) formation and maintenance of a stable
      replication fork during the elongation phase of chromosomal DNA replication.

PMID- 19605347
TI  - Pif1 helicase lengthens some Okazaki fragment flaps necessitating Dna2
      nuclease/helicase action in the two-nuclease processing pathway.
AB  - We have developed a system to reconstitute all of the proposed steps of Okazaki
      fragment processing using purified yeast proteins and model substrates. DNA
      polymerase delta was shown to extend an upstream fragment to displace a
      downstream fragment into a flap. In most cases, the flap was removed by flap
      endonuclease 1 (FEN1), in a reaction required to remove initiator RNA in vivo.
      The nick left after flap removal could be sealed by DNA ligase I to complete
      fragment joining. An alternative pathway involving FEN1 and the nuclease/helicase
      Dna2 has been proposed for flaps that become long enough to bind replication
      protein A (RPA). RPA binding can inhibit FEN1, but Dna2 can shorten RPA-bound
      flaps so that RPA dissociates. Recent reconstitution results indicated that Pif1
      helicase, a known component of fragment processing, accelerated flap
      displacement, allowing the inhibitory action of RPA. In results presented here,
      Pif1 promoted DNA polymerase delta to displace strands that achieve a length to
      bind RPA, but also to be Dna2 substrates. Significantly, RPA binding to long
      flaps inhibited the formation of the final ligation products in the reconstituted
      system without Dna2. However, Dna2 reversed that inhibition to restore efficient
      ligation. These results suggest that the two-nuclease pathway is employed in
      cells to process long flap intermediates promoted by Pif1.

PMID- 19605348
TI  - Phosphorylated intrinsically disordered region of FACT masks its nucleosomal DNA
      binding elements.
AB  - FACT is a heterodimer of SPT16 and SSRP1, which each contain several conserved
      regions in the primary structure. The interaction of FACT with nucleosomes
      induces chromatin remodeling through the combinatorial action of its distinct
      functional protein regions. However, there is little mechanistic insight into how
      these regions cooperatively contribute to FACT functions, particularly regarding
      the recognition of nucleosomal DNA. Here, we report the identification of novel
      phosphorylation sites of Drosophila melanogaster FACT (dFACT) expressed in Sf9
      cells. These sites are densely concentrated in the acidic intrinsically
      disordered (ID) region of the SSRP1 subunit and control nucleosomal DNA binding
      by dFACT. This region and the adjacent segment of the HMG domain form weak
      electrostatic intramolecular interactions, which is reinforced by the
      phosphorylation, thereby blocking DNA binding competitively. Importantly, this
      control mechanism appears to support rapid chromatin transactions during early
      embryogenesis through the dephosphorylation of some sites in the maternally
      transmitted dSSRP1.

PMID- 19605349
TI  - A unitary anesthetic binding site at high resolution.
AB  - Propofol is the most widely used injectable general anesthetic. Its targets
      include ligand-gated ion channels such as the GABA(A) receptor, but such receptor
      channel complexes remain challenging to study at atomic resolution. Until
      structural biology methods advance to the point of being able to deal with
      systems such as the GABA(A) receptor, it will be necessary to use more tractable
      surrogates to probe the molecular details of anesthetic recognition. We have
      previously shown that recognition of inhalational general anesthetics by the
      model protein apoferritin closely mirrors recognition by more complex and
      clinically relevant protein targets; here we show that apoferritin also binds
      propofol and related GABAergic anesthetics, and that the same binding site
      mediates recognition of both inhalational and injectable anesthetics. Apoferritin
      binding affinities for a series of propofol analogs were found to be strongly
      correlated with the ability to potentiate GABA responses at GABA(A) receptors,
      validating this model system for injectable anesthetics. High resolution x-ray
      crystal structures reveal that, despite the presence of hydrogen bond donors and
      acceptors, anesthetic recognition is mediated largely by van der Waals forces and
      the hydrophobic effect. Molecular dynamics simulations indicate that the ligands
      undergo considerable fluctuations about their equilibrium positions. Finally,
      apoferritin displays both structural and dynamic responses to anesthetic binding,
      which may mimic changes elicited by anesthetics in physiologic targets like ion
      channels.

PMID- 19605350
TI  - Interaction of Mycobacterium tuberculosis CYP130 with heterocyclic arylamines.
AB  - The Mycobacterium tuberculosis P450 enzymes are of interest for their
      pharmacological development potential, as evidenced by their susceptibility to
      inhibition by antifungal azole drugs that normally target sterol 14alpha
      demethylase (CYP51). Although antifungal azoles show promise, direct screening of
      compounds against M. tuberculosis P450 enzymes may identify novel, more potent,
      and selective inhibitory scaffolds. Here we report that CYP130 from M.
      tuberculosis has a natural propensity to bind primary arylamines with particular
      chemical architectures. These compounds were identified via a high throughput
      screen of CYP130 with a library of synthetic organic molecules. As revealed by
      subsequent x-ray structure analysis, selected compounds bind in the active site
      by Fe-coordination and hydrogen bonding of the arylamine group to the carbonyl
      oxygen of Gly(243). As evidenced by the binding of structural analogs, the
      primary arylamine group is indispensable, but synergism due to hydrophobic
      contacts between the rest of the molecule and protein amino acid residues is
      responsible for a binding affinity comparable with that of the antifungal azole
      drugs. The topology of the CYP130 active site favors angular coordination of the
      arylamine group over the orthogonal coordination of azoles. Upon substitution of
      Gly(243) by an alanine, the binding mode of azoles and some arylamines reverted
      from type II to type I because of hydrophobic and steric interactions with the
      alanine side chain. We suggest a role for the conserved Ala(Gly)(243)-Gly(244)
      motif in the I-helix in modulating both the binding affinity of the axial water
      ligand and the ligand selectivity of cytochrome P450 enzymes.

PMID- 19605351
TI  - HSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA
      damage response.
AB  - hSSB1 (human single strand DNA-binding protein 1) has been shown to participate
      in homologous recombination (HR)-dependent repair of DNA double strand breaks
      (DSBs) and ataxia telangiectasia-mutated (ATM)-mediated checkpoint pathways. Here
      we present evidence that hSSB2, a homolog of hSSB1, plays a role similar to hSSB1
      in DNA damage-response pathways. This was evidenced by findings that hSSB2
      depleted cells resemble hSSB1-depleted cells in hypersensitivity to DNA-damaging
      reagents, reduced efficiency in HR-dependent repair of DSBs, and defective ATM
      dependent phosphorylation. Notably, hSSB1 and hSSB2 form separate complexes with
      two identical proteins, INTS3 and hSSBIP1 (C9ORF80). Cells depleted of INTS3 and
      hSSBIP1 also exhibited hypersensitivity to DNA damage reagents, chromosomal
      instability, and reduced ATM-dependent phosphorylation. hSSBIP1 was rapidly
      recruited to laser-induced DSBs, a feature also similar to that reported for
      hSSB1. Depletion of INTS3 decreased the stability of hSSB1 and hSSBIP1,
      suggesting that INTS3 may provide a scaffold to allow proper assembly of the hSSB
      complexes. Thus, our data demonstrate that hSSB1 and hSSB2 form two separate
      complexes with similar structures, and both are required for efficient HR
      dependent repair of DSBs and ATM-dependent signaling pathways.

PMID- 19605352
TI  - Mechanisms of activity-dependent plasticity in cellular nitric oxide-cGMP
      signaling.
AB  - Cellular responsiveness to nitric oxide (NO) is shaped by past history of NO
      exposure. The mechanisms behind this plasticity were explored using rat platelets
      in vitro, specifically to determine the relative contributions made by
      desensitization of NO receptors, which couple to cGMP formation, and by
      phosphodiesterase-5 (PDE5), which is activated by cGMP and also hydrolyzes it.
      Repeated delivery of brief NO pulses (50 nM peak) at 1-min intervals resulted in
      a progressive loss of the associated cGMP responses, which was the combined
      consequence of receptor desensitization and PDE5 activation, with the former
      dominating. Delivery of pulses of differing amplitude showed that NO stimulated
      and desensitized receptors with similar potency (EC50 = 10-20 nM). PDE5
      activation was highly sensitive to NO, with a single pulse peaking at 2 nM being
      sufficient to evoke a 50% loss of response to a subsequent near-maximal NO pulse.
      However, the activated state of the PDE subsided quickly after removal of NO, the
      half-time for recovery being 25 s. In contrast, receptor desensitization reverted
      much more slowly, the half-time being 16 min. Accordingly, with long (20-min)
      exposures, NO concentrations as low as 600 pM provoked significant
      desensitization. The results indicate that PDE5 activation and receptor
      desensitization subserve distinct short term and longer term roles as mediators
      of plasticity in NO-cGMP signaling. A kinetic model explicitly describing the
      complex interplay between NO concentration, cGMP synthesis, PDE5 activation, and
      the resulting cGMP accumulation successfully simulated the present and previous
      data.

PMID- 19605354
TI  - Germ line-governed recognition of a cancer epitope by an immunodominant human T
      cell receptor.
AB  - CD8(+) T-cells specific for MART-1-(26-35), a dominant melanoma epitope
      restricted by human leukocyte antigen (HLA)-A*0201, are exceptionally common in
      the naive T-cell repertoire. Remarkably, the TRAV12-2 gene is used to encode the
      T-cell receptor alpha (TCRalpha) chain in >87% of these T-cells. Here, the
      molecular basis for this genetic bias is revealed from the structural and
      thermodynamic properties of an archetypal TRAV12-2-encoded TCR complexed to the
      clinically relevant heteroclitic peptide, ELAGIGILTV, bound to HLA-A*0201 (A2
      ELA). Unusually, the TRAV12-2 germ line-encoded regions of the TCR dominate the
      major atomic contacts with the peptide at the TCR/A2-ELA interface. This "innate"
      pattern of antigen recognition probably explains the unique characteristics and
      extraordinary frequencies of CD8(+) T-cell responses to this epitope.

PMID- 19605353
TI  - Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and
      P2X receptors.
AB  - The role of endogenous inducers of inflammation is poorly understood. To produce
      the proinflammatory master cytokine interleukin (IL)-1beta, macrophages need
      double stimulation with ligands to both Toll-like receptors (TLRs) for IL-1beta
      gene transcription and nucleotide-binding oligomerization domain-like receptors
      for activation of the inflammasome. It is particularly intriguing to define how
      this complex regulation is mediated in the absence of an infectious trigger.
      Biglycan, a ubiquitous leucine-rich repeat proteoglycan of the extracellular
      matrix, interacts with TLR2/4 on macrophages. The objective of this study was to
      define the role of biglycan in the synthesis and activation of IL-1beta. Here we
      show that in macrophages, soluble biglycan induces the NLRP3/ASC inflammasome,
      activating caspase-1 and releasing mature IL-1beta without the need for
      additional costimulatory factors. This is brought about by the interaction of
      biglycan with TLR2/4 and purinergic P2X(4)/P2X(7) receptors, which induces
      receptor cooperativity. Furthermore, reactive oxygen species formation is
      involved in biglycan-mediated activation of the inflammasome. By signaling
      through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta
      mRNA. Both in a model of non-infectious inflammatory renal injury (unilateral
      ureteral obstruction) and in lipopolysaccharide-induced sepsis, biglycan
      deficient mice displayed lower levels of active caspase-1 and mature IL-1beta in
      the kidney, lung, and circulation. Our results provide evidence for direct
      activation of the NLRP3 inflammasome by biglycan and describe a fundamental
      paradigm of how tissue stress or injury is monitored by innate immune receptors
      detecting the release of the extracellular matrix components and turning such a
      signal into a robust inflammatory response.

PMID- 19605355
TI  - Synthesis of dideoxymycobactin antigens presented by CD1a reveals T cell fine
      specificity for natural lipopeptide structures.
AB  - Mycobacterium tuberculosis survival in cells requires mycobactin siderophores.
      Recently, the search for lipid antigens presented by the CD1a antigen-presenting
      protein led to the discovery of a mycobactin-like compound, dideoxymycobactin
      (DDM). Here we synthesize DDMs using solution phase and solid phase peptide
      synthesis chemistry. Comparison of synthetic standards to natural mycobacterial
      mycobactins by nuclear magnetic resonance and mass spectrometry allowed
      identification of an unexpected alpha-methyl serine unit in natural DDM. This
      finding further distinguishes these pre-siderophores as foreign compounds
      distinct from conventional peptides, and we provide evidence that this chemical
      variation influences the T cell response. One synthetic DDM recapitulated natural
      structures and potently stimulated T cells, making it suitable for patient
      studies of CD1a in infectious disease. DDM analogs differing in the
      stereochemistry of their butyrate or oxazoline moieties were not recognized by
      human T cells. Therefore, we conclude that T cells show precise specificity for
      both arms of the peptide, which are predicted to lie at the CD1a-T cell receptor
      interface.

PMID- 19605356
TI  - Porphyrins promote the association of GENOMES UNCOUPLED 4 and a Mg-chelatase
      subunit with chloroplast membranes.
AB  - In plants, chlorophylls and other tetrapyrroles are synthesized from a branched
      pathway that is located within chloroplasts. GUN4 (GENOMES UNCOUPLED 4)
      stimulates chlorophyll biosynthesis by activating Mg-chelatase, the enzyme that
      commits porphyrins to the chlorophyll branch. GUN4 stimulates Mg-chelatase by a
      mechanism that involves binding the ChlH subunit of Mg-chelatase, as well as a
      substrate (protoporphyrin IX) and product (Mg-protoporphyrin IX) of Mg-chelatase.
      We chose to test whether GUN4 might also affect interactions between Mg-chelatase
      and chloroplast membranes, the site of chlorophyll biosynthesis. To test this
      idea, we induced chlorophyll precursor levels in purified pea chloroplasts by
      feeding these chloroplasts with 5-aminolevulinic acid, determined the relative
      levels of GUN4 and Mg-chelatase subunits in soluble and membrane-containing
      fractions derived from these chloroplasts, and quantitated Mg-chelatase activity
      in membranes isolated from these chloroplasts. We also monitored GUN4 levels in
      the soluble and membrane-containing fractions derived from chloroplasts fed with
      various porphyrins. Our results indicate that 5-aminolevulinic acid feeding
      stimulates Mg-chelatase activity in chloroplast membranes and that the porphyrin
      bound forms of GUN4 and possibly ChlH associate most stably with chloroplast
      membranes. These findings are consistent with GUN4 stimulating chlorophyll
      biosynthesis not only by activating Mg-chelatase but also by promoting
      interactions between ChlH and chloroplast membranes.

PMID- 19605357
TI  - Nuclear degradation of Wilms tumor 1-associating protein and survivin splice
      variant switching underlie IGF-1-mediated survival.
AB  - WTAP (Wilms tumor 1-associating protein) is a recently identified nuclear protein
      that is essential for mouse embryo development. The Drosophila homolog of WTAP,
      Fl(2)d, regulates pre-mRNA splicing; however, the role of WTAP in mammalian cells
      is uncertain. To elucidate a context for WTAP action, we screened growth and
      survival factors for their effects on WTAP expression in vascular smooth muscle
      cells (SMCs), a cell type previously found to express WTAP dynamically. This
      revealed that insulin-like growth factor-1 (IGF-1) uniquely reduced WTAP
      abundance. This decline in WTAP proved to be necessary for IGF-1 to confer its
      antiapoptotic properties, which were blocked by transducing the WTAP gene into
      SMCs. WTAP down-regulation by IGF-1 was mediated by an IGF-1 receptor
      phosphatidylinositol 3-kinase-Akt signaling axis that directed WTAP degradation
      via a nuclear 26 S proteasome. Moreover, by promoting the degradation of WTAP,
      IGF-1 shifted the pre-mRNA splicing program for the survival factor, survivin, to
      reduce expression of survivin-2B, which is proapoptotic, and increase expression
      of survivin, which is antiapoptotic. Knockdown of survivin-2B rescued the ability
      of IGF-1 to promote survival when WTAP was overexpressed. These data uncover a
      novel regulatory cascade for human SMC survival based on adjusting the nuclear
      abundance of WTAP to define the splice variant balance among survivin isoforms.

PMID- 19605358
TI  - Bacterial-type phosphoenolpyruvate carboxylase (PEPC) functions as a catalytic
      and regulatory subunit of the novel class-2 PEPC complex of vascular plants.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated anaplerotic enzyme
      situated at a major branch point of the plant C metabolism. Two distinct
      oligomeric classes of PEPC occur in the triglyceride-rich endosperm of developing
      castor oil seeds (COS). Class-1 PEPC is a typical homotetramer composed of
      identical 107-kDa plant-type PEPC (PTPC) subunits (encoded by RcPpc3), whereas
      the novel Class-2 PEPC 910-kDa hetero-octameric complex arises from a tight
      interaction between Class-1 PEPC and distantly related 118-kDa bacterial-type
      PEPC (BTPC) polypeptides (encoded by RcPpc4). Here, COS BTPC was expressed from
      full-length RcPpc4 cDNA in Escherichia coli as an active PEPC that exhibited
      unusual properties relative to PTPCs, including a tendency to form large
      aggregates, enhanced thermal stability, a high K(m)((PEP)), and insensitivity to
      metabolite effectors. A chimeric 900-kDa Class-2 PEPC hetero-octamer having a 1:1
      stoichiometry of BTPC:PTPC subunits was isolated from a mixture of clarified
      extracts containing recombinant RcPPC4 and an Arabidopsis thaliana Class-1 PEPC
      (the PTPC, AtPPC3). The purified Class-2 PEPC exhibited biphasic PEP saturation
      kinetics with high and low affinity sites attributed to its AtPPC3 and RcPPC4
      subunits, respectively. The RcPPC4 subunits: (i) catalyzed the majority of the
      Class-2 PEPC V(max), particularly in the presence of the inhibitor l-malate, and
      (ii) also functioned as Class-2 PEPC regulatory subunits by modulating PEP
      binding and catalytic potential of its AtPPC3 subunits. BTPCs appear to associate
      with PTPCs to form stable Class-2 PEPC complexes in vivo that are hypothesized to
      maintain high flux from PEP under physiological conditions that would otherwise
      inhibit Class-1 PEPCs.

PMID- 19605359
TI  - Effect of conformational dynamics on substrate recognition and specificity as
      probed by the introduction of a de novo disulfide bond into cytochrome P450 2B1.
AB  - The conformational dynamics of cytochrome P450 2B1 (CYP2B1) were investigated
      through the introduction of a disulfide bond to link the I- and K-helices by
      generation of a double Cys variant, Y309C/S360C. The consequences of the
      disulfide bonding were examined both experimentally and in silico by molecular
      dynamics simulations. Under high hydrostatic pressures, the partial inactivation
      volume for the Y309C/S360C variant was determined to be -21 cm3mol(-1), which is
      more than twice as much as those of the wild type (WT) and single Cys variants
      (Y309C, S360C). This result indicates that the engineered disulfide bond has
      substantially reduced the protein plasticity of the Y309C/S360C variant. Under
      steady-state turnover conditions, the S360C variant catalyzed the N-demethylation
      of benzphetamine and O-deethylation of 7-ethoxy-trifluoromethylcoumarin as the WT
      did, whereas the Y309C variant retained only 39% of the N-demethylation activity
      and 66% of the O-deethylation activity compared with the WT. Interestingly, the
      Y309C/S360C variant restored the N-demethylation activity to the same level as
      that of the WT but decreased the O-deethylation activity to only 19% of the WT.
      Furthermore, the Y309C/S360C variant showed increased substrate specificity for
      testosterone over androstenedione. Molecular dynamics simulations revealed that
      the engineered disulfide bond altered substrate access channels. Taken together,
      these results suggest that protein dynamics play an important role in regulating
      substrate entry and recognition.

PMID- 19605360
TI  - Identification of a short Spir interaction sequence at the C-terminal end of
      formin subgroup proteins.
AB  - The actin nucleation factors Spire and Cappuccino interact with each other and
      regulate essential cellular events during Drosophila oogenesis in a cooperative
      fashion. The interaction blocks formin actin nucleation activity and enhances the
      Spire activity. Analogous to Spire and Cappuccino, the mammalian homologs Spir-1
      and formin-2 show a regulatory interaction. To get an understanding of the nature
      of the Spir-formin cooperation, we have analyzed the interaction biochemically
      and biophysically. Our data shows that the association of Spir-1 and formin-2 is
      not significantly mediated by binding of the Spir-1-KIND domain to the formin FH2
      core domain. Instead, a short sequence motif C-terminal adjacent to the formin-2
      FH2 domain could be characterized that mediates the interaction and is conserved
      among the members of the Fmn subgroup of formins. In line with this, we found
      that both mammalian Spir proteins, Spir-1 and Spir-2, interact with mammalian Fmn
      subgroup proteins formin-1 and formin-2.

PMID- 19605361
TI  - MEK5/ERK5 signaling modulates endothelial cell migration and focal contact
      turnover.
AB  - The formation of new blood vessels from pre-existing ones requires highly
      coordinated restructuring of endothelial cells (EC) and the surrounding
      extracellular matrix. Directed EC migration is a central step in this process and
      depends on cellular signaling cascades that initiate and control the structural
      rearrangements. On the basis of earlier findings that ERK5 deficiency in mouse EC
      results in massive defects in vessel architecture, we focused on the impact of
      the MEK5/ERK5 signaling pathway on EC migration. Using a retroviral gene transfer
      approach, we found that constitutive activation of MEK5/ERK5 signaling strongly
      inhibits EC migration and results in massive morphological changes. The area
      covered by spread EC was dramatically enlarged, accompanied by an increase in
      focal contacts and altered organization of actin filaments. Consequently, cells
      were more rigid and show reduced motility. This phenotype was most likely based
      on decreased focal contact turnover caused by reduced expression of p130Cas, a
      key player in directed cell migration. We demonstrate for the first time that
      ERK5 signaling not only is involved in EC survival and stress response but also
      controls migration and morphology of EC.

PMID- 19605362
TI  - Actin isoform-specific conformational differences observed with
      hydrogen/deuterium exchange and mass spectrometry.
AB  - Actin can exist in multiple conformations necessary for normal function. Actin
      isoforms, although highly conserved in sequence, exhibit different biochemical
      properties and cellular roles. We used amide proton hydrogen/deuterium (HD)
      exchange detected by mass spectrometry to analyze conformational differences
      between Saccharomyces cerevisiae and muscle actins in the G and F forms to gain
      insight into these differences. We also utilized HD exchange to study interdomain
      and allosteric communication in yeast-muscle hybrid actins to better understand
      the conformational dynamics of actin. Areas showing differences in HD exchange
      between G- and F-actins are areas of intermonomer contacts, consistent with the
      current filament models. Our results showed greater exchange for yeast G-actin
      compared with muscle actin in the barbed end pivot region and areas in subdomains
      1 and 2 and for F-actin in monomer-monomer contact areas. These results suggest
      greater flexibility of the yeast actin monomer and filament compared with muscle
      actin. For hybrid G-actins, the muscle-like and yeastlike parts of the molecule
      generally showed exchange characteristics resembling their parent actins. A few
      exceptions were a peptide on top of subdomain 2 and the pivot region between
      subdomains 1 and 3 with muscle actin-like exchange characteristics although the
      areas were yeastlike. These results demonstrate that there is cross-talk between
      subdomains 1 and 2 and the large and small domains. Hybrid F-actin data showing
      greater exchange compared with both yeast and muscle actins are consistent with
      mismatched yeast-muscle interfaces resulting in decreased stability of the hybrid
      filament contacts.

PMID- 19605364
TI  - Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins.
AB  - Thioredoxin-interacting protein (Txnip), originally characterized as an inhibitor
      of thioredoxin, is now known to be a critical regulator of glucose metabolism in
      vivo. Txnip is a member of the alpha-arrestin protein family; the alpha-arrestins
      are related to the classical beta-arrestins and visual arrestins. Txnip is the
      only alpha-arrestin known to bind thioredoxin, and it is not known whether the
      metabolic effects of Txnip are related to its ability to bind thioredoxin or
      related to conserved alpha-arrestin function. Here we show that wild type Txnip
      and Txnip C247S, a Txnip mutant that does not bind thioredoxin in vitro, both
      inhibit glucose uptake in mature adipocytes and in primary skin fibroblasts.
      Furthermore, we show that Txnip C247S does not bind thioredoxin in cells, using
      thiol alkylation to trap the Txnip-thioredoxin complex. Because Txnip function
      was independent of thioredoxin binding, we tested whether inhibition of glucose
      uptake was conserved in the related alpha-arrestins Arrdc4 and Arrdc3. Both Txnip
      and Arrdc4 inhibited glucose uptake and lactate output, while Arrdc3 had no
      effect. Structure-function analysis indicated that Txnip and Arrdc4 inhibit
      glucose uptake independent of the C-terminal WW-domain binding motifs, recently
      identified as important in yeast alpha-arrestins. Instead, regulation of glucose
      uptake was intrinsic to the arrestin domains themselves. These data demonstrate
      that Txnip regulates cellular metabolism independent of its binding to
      thioredoxin and reveal the arrestin domains as crucial structural elements in
      metabolic functions of alpha-arrestin proteins.

PMID- 19605363
TI  - Dynamin2 GTPase and cortactin remodel actin filaments.
AB  - The large GTPase dynamin, best known for its activities that remodel membranes
      during endocytosis, also regulates F-actin-rich structures, including podosomes,
      phagocytic cups, actin comet tails, subcortical ruffles, and stress fibers. The
      mechanisms by which dynamin regulates actin filaments are not known, but an
      emerging view is that dynamin influences F-actin via its interactions with
      proteins that interact directly or indirectly with actin filaments. We show here
      that dynamin2 GTPase activity remodels actin filaments in vitro via a mechanism
      that depends on the binding partner and F-actin-binding protein, cortactin.
      Tightly associated actin filaments cross-linked by dynamin2 and cortactin became
      loosely associated after GTP addition when viewed by transmission electron
      microscopy. Actin filaments were dynamically unraveled and fragmented after GTP
      addition when viewed in real time using total internal reflection fluorescence
      microscopy. Cortactin stimulated the intrinsic GTPase activity of dynamin2 and
      maintained a stable link between actin filaments and dynamin2, even in the
      presence of GTP. Filaments remodeled by dynamin2 GTPase in vitro exhibit enhanced
      sensitivity to severing by the actin depolymerizing factor, cofilin, suggesting
      that GTPase-dependent remodeling influences the interactions of actin regulatory
      proteins and F-actin. The global organization of the actomyosin cytoskeleton was
      perturbed in U2-OS cells depleted of dynamin2, implicating dynamin2 in remodeling
      actin filaments that comprise supramolecular F-actin arrays in vivo. We conclude
      that dynamin2 GTPase remodels actin filaments and plays a role in orchestrating
      the global actomyosin cytoskeleton.

PMID- 19605365
TI  - Normalization and statistical analysis of quantitative proteomics data generated
      by metabolic labeling.
AB  - Comparative proteomics is a powerful analytical method for learning about the
      responses of biological systems to changes in growth parameters. To make
      confident inferences about biological responses, proteomics approaches must
      incorporate appropriate statistical measures of quantitative data. In the present
      work we applied microarray-based normalization and statistical analysis
      (significance testing) methods to analyze quantitative proteomics data generated
      from the metabolic labeling of a marine bacterium (Sphingopyxis alaskensis).
      Quantitative data were generated for 1,172 proteins, representing 1,736 high
      confidence protein identifications (54% genome coverage). To test approaches for
      normalization, cells were grown at a single temperature, metabolically labeled
      with (14)N or (15)N, and combined in different ratios to give an artificially
      skewed data set. Inspection of ratio versus average (MA) plots determined that a
      fixed value median normalization was most suitable for the data. To determine an
      appropriate statistical method for assessing differential abundance, a -fold
      change approach, Student's t test, unmoderated t test, and empirical Bayes
      moderated t test were applied to proteomics data from cells grown at two
      temperatures. Inverse metabolic labeling was used with multiple technical and
      biological replicates, and proteomics was performed on cells that were combined
      based on equal optical density of cultures (providing skewed data) or on cell
      extracts that were combined to give equal amounts of protein (no skew). To
      account for arbitrarily complex experiment-specific parameters, a linear modeling
      approach was used to analyze the data using the limma package in R/Bioconductor.
      A high quality list of statistically significant differentially abundant proteins
      was obtained by using lowess normalization (after inspection of MA plots) and
      applying the empirical Bayes moderated t test. The approach also effectively
      controlled for the number of false discoveries and corrected for the multiple
      testing problem using the Storey-Tibshirani false discovery rate (Storey, J. D.,
      and Tibshirani, R. (2003) Statistical significance for genomewide studies. Proc.
      Natl. Acad. Sci. U.S.A. 100, 9440-9445). The approach we have developed is
      generally applicable to quantitative proteomics analyses of diverse biological
      systems.

PMID- 19605367
TI  - Impact of resurvey non-response on the associations between baseline risk factors
      and cardiovascular disease mortality: prospective cohort study.
AB  - BACKGROUND: Selection bias in observational epidemiology--the notion that people
      who participate in a study are fundamentally different from those who do not--is
      a perennial concern. In cohort studies, a potentially important but little
      investigated manifestation of selection bias is the distortion of the exposure
      disease relationship according to participation status. METHODS: Seven years
      after the original UK Health and Lifestyle Survey (HALS1; N = 6484), attempts
      were made to resurvey participants (HALS2). The baseline characteristics,
      mortality experience following the completion of HALS2 and, finally, the baseline
      risk factor-cardiovascular disease (CVD) mortality gradients in HALS2 non
      participants (N = 1894) and participants (N = 4590) were compared. RESULTS:
      Resurvey non-participants, based on data from HALS1, were younger, were of lower
      social class and had a lower prevalence of hypertension or self-reported limiting
      long-standing illness, but a higher prevalence of psychological distress (p < or
      = 0.027). The risk of death from future CVD was significantly higher in those
      baseline study members who did not participate in HALS2. However, the magnitude
      of the association between a series of risk factors and CVD mortality was
      essentially the same in the HALS2 non-participants and participants (p value for
      interaction > or = 0.108). CONCLUSION: In the present cohort study, non-response
      at resurvey did not bias the observed associations between baseline risk factors
      and later CVD mortality. Future studies should also examine the impact of non
      response to baseline surveys on these relationships.

PMID- 19605368
TI  - Socioeconomic differences in takeaway food consumption and their contribution to
      inequalities in dietary intakes.
AB  - BACKGROUND: Takeaway consumption has been increasing and may contribute to
      socioeconomic inequalities in overweight/obesity and chronic disease. This study
      examined socioeconomic differences in takeaway consumption patterns and their
      contributions to dietary intake inequalities. METHOD: Cross-sectional dietary
      intake data from adults aged between 25 and 64 years from the Australian National
      Nutrition Survey (n = 7319, 61% response rate). Twenty-four-hour dietary recalls
      ascertained intakes of takeaway food, nutrients and fruit and vegetables.
      Education was used as a socioeconomic indicator. Data were analysed using
      logistic regression and general linear models. RESULTS: Thirty-two per cent (n =
      2327) consumed takeaway foods in the 24-hour period. Lower educated participants
      were less likely than their higher educated counterparts to have consumed total
      takeaway foods (OR 0.64; 95% CI 0.52 to 0.80). Of those consuming takeaway foods,
      the lowest educated group was more likely to have consumed "less healthy"
      takeaway choices (OR 2.55; 95% CI 1.73 to 3.77), and less likely to have consumed
      "healthy" choices (OR 0.52; 95% CI 0.36 to 0.75). Takeaway foods made a greater
      contribution to energy, total fat, saturated fat and fibre intakes among lower
      than among higher educated groups. Lower likelihood of fruit and vegetable
      intakes were observed among "less healthy" takeaway consumers, whereas a greater
      likelihood of their consumption was found among "healthy" takeaway consumers.
      CONCLUSIONS: Total and the types of takeaway foods consumed may contribute to
      socioeconomic inequalities in intakes of energy, total and saturated fats.
      However, takeaway consumption is unlikely to be a factor contributing to the
      lower fruit and vegetable intakes among socioeconomically disadvantaged groups.

PMID- 19605366
TI  - A new approach for quantitative phosphoproteomic dissection of signaling pathways
      applied to T cell receptor activation.
AB  - Reversible protein phosphorylation plays a pivotal role in the regulation of
      cellular signaling pathways. Current approaches in phosphoproteomics focus on
      analysis of the global phosphoproteome in a single cellular state or of receptor
      stimulation time course experiments, often with a restricted number of time
      points. Although these studies have provided some insights into newly discovered
      phosphorylation sites that may be involved in pathways, they alone do not provide
      enough information to make precise predictions of the placement of individual
      phosphorylation events within a signaling pathway. Protein disruption and site
      directed mutagenesis are essential to clearly define the precise biological roles
      of the hundreds of newly discovered phosphorylation sites uncovered in modern
      proteomics experiments. We have combined genetic analysis with quantitative
      proteomic methods and recently developed visual analysis tools to dissect the
      tyrosine phosphoproteome of isogenic Zap-70 tyrosine kinase null and
      reconstituted Jurkat T cells. In our approach, label-free quantitation using
      normalization to copurified phosphopeptide standards is applied to assemble high
      density temporal data within a single cell type, either Zap-70 null or
      reconstituted cells, providing a list of candidate phosphorylation sites that
      change in abundance after T cell stimulation. Stable isotopic labeling of amino
      acids in cell culture (SILAC) ratios are then used to compare Zap-70 null and
      reconstituted cells across a time course of receptor stimulation, providing
      direct information about the placement of newly observed phosphorylation sites
      relative to Zap-70. These methods are adaptable to any cell culture signaling
      system in which isogenic wild type and mutant cells have been or can be derived
      using any available phosphopeptide enrichment strategy.

PMID- 19605369
TI  - Ventricular mass index correlates with pulmonary artery pressure and predicts
      survival in suspected systemic sclerosis-associated pulmonary arterial
      hypertension.
AB  - OBJECTIVE: The ventricular mass index (VMI) has been proposed as a diagnostic
      tool for the assessment of patients with suspected pulmonary hypertension (PH).
      We hypothesized that in patients with SSc it may predict the presence or absence
      of PH. METHODS: Details of all consecutive SSc patients undergoing MRI and right
      heart catheterization were collected prospectively. Subsequently, the VMI for all
      patients was calculated, and further baseline data were collected. RESULTS: Data
      for 40 patients, 28 of whom were diagnosed with PH at rest (PH(REST)), were
      analysed. VMI correlated strongly with mean pulmonary artery pressure (mPAP; r =
      0.79). Using a VMI threshold of 0.56, positive predictive value (PPV) for
      PH(REST) was 88% and negative predictive value (NPV) was 100%. Using a threshold
      of 0.7, PPV was found to be 100% and NPV 53%. Echocardiographically obtained
      tricuspid gradient (TG) also demonstrated a strong correlation with mPAP. Two
      year survival in patients with VMI <0.7 and > or =0.7 was 91 and 43%,
      respectively (P < 0.001). CONCLUSION: VMI correlates well with mPAP in patients
      with SSc and may have a role in non-invasively excluding clinically significant
      PH in breathless SSc patients in whom echocardiographic screening has failed.
      Further study in larger groups of patients is justified.

PMID- 19605371
TI  - The influence of diffuse idiopathic skeletal hyperostosis on bone mineral density
      measurements of the spine.
AB  - OBJECTIVES: BMD has been described to be increased in patients with DISH. The
      contribution of the ossified anterior longitudinal ligament (ALL) on vertebral
      body BMD is currently unknown. We investigated the influence of DISH on BMD
      measurements using an experimental DXA scanning protocol. METHODS: Ten DISH
      specimens and 10 matched human cadaveric spines were used. After assessment of
      the localization and orientation of the ossified ALL with CT, BMD was measured
      using an experimental DXA protocol, exploiting the asymmetry of DISH in the
      thoracic spine. For controls, identical orientations were used and both groups
      were compared for differences in BMD. RESULTS: Specimens with DISH displayed a
      significantly higher BMD than their matched controls when the ossified ALL was
      present in the scanning field. Measurements of the left half of the spine were
      comparable for DISH specimens and controls (P = 0.446). The right-left difference
      in anteroposterior view was statistically significant within DISH specimens (P =
      0.001), but not in controls (P = 0.825). CONCLUSIONS: The variability in
      measurements in different scanning orientations suggests a substantial
      contribution of the ossified ALL to the total BMD in DISH specimens, ranging from
      23.6 to 39.0%. Vertebral body BMD does not seem to be increased, as demonstrated
      by comparable BMDs in the unaffected left half of the spine. It is suggested that
      routine anteroposterior DXA scanning may overestimate the true vertebral body BMD
      in DISH patients.

PMID- 19605370
TI  - Sensitivity to change of the modified Rodnan skin score in diffuse systemic
      sclerosis--assessment of individual body sites in two large randomized controlled
      trials.
AB  - OBJECTIVE: The modified Rodnan skin score (MRSS) is a standard outcome measure
      for skin disease in SSc and calculated by summation of skin thickness in 17
      different body sites (total score = 51). Our objective was to evaluate the
      sensitivity of change over time of individual body sites used in the calculation
      of total MRSS. METHODS: We analysed two randomized placebo controlled clinical
      trials investigating the effect of either recombinant human relaxin or type I
      oral collagen in dcSSc. Both trials used MRSS as the primary outcome measure. We
      used a change of >10 mm (on a 0-100 VAS) in the patient global assessment (PGA)
      as the clinically important improvement. We calculated the mean change and the
      effect size (ES) for each individual body site used in the total MRSS for each
      study. Magnitude of ES was assessed using Cohen's rule of thumb for ES. RESULTS:
      In the relaxin and collagen studies, 71 of 199 patients (36%) and 54 of 129 (42%)
      of patients had an improvement >10 mm on the PGA at 6 and 12 months,
      respectively. Total MRSS had large ES in both studies (0.85-0.98); the chest,
      forearms and hands had moderate ES (0.50-0.74); and the lower extremities, face,
      abdomen and fingers had small ES (0.16-0.49). CONCLUSION: Certain body sites
      (hands, forearms and chest) are more sensitive to change compared with other body
      sites in two randomized clinical trials. It remains to be seen whether decreasing
      the number of body sites by exclusion of relatively static areas would further
      increase the sensitivity to change over time of the total MRSS.

PMID- 19605373
TI  - Improvements of muscle strength predicted benefits in HRQOL and postural balance
      in women with fibromyalgia: an 8-month randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether changes in muscle strength due to 32 weeks of
      supervised aquatic training predicted improvements on health-related quality of
      life (HRQOL). METHODS: Thirty women with FM aged 50.8 +/- 8.7 years were randomly
      assigned to an experimental group (n = 15), performing 3 weekly sessions of 60
      min of warm-water exercise; or to a control group (n = 15). HRQOL was evaluated
      using the Short Form 36 Health Survey (SF-36). Maximal unilateral isokinetic
      strength was measured at 60 degrees/s and 210 degrees/s in the knee extensors and
      flexors in concentric action and at 60 degrees/s in knee extensors eccentric
      action. Postural balance was evaluated using the one-leg stance, eyes closed.
      RESULTS: After 32 weeks of water exercise therapy, statistically significant
      improvements occurred in concentric knee flexors and extensors strength at 60
      degrees/s, in eccentric knee extensors and in postural balance. The treatment led
      to additional improvements in physical function, role physical problems, body
      pain, general health, vitality, role emotional problems and mental health
      dimensions of SF-36. Gains in the concentric knee flexors strength predicted
      improvements in role of physical problems, whereas those in concentric knee
      extensors did the same for mental health and role emotional problems. Gains in
      eccentric knee extensors strength predicted improvements in postural balance.
      CONCLUSIONS: A long-lasting exercise therapy in warm water produced relevant
      gains in muscle strength at low velocities of movements, some of which predicted
      improvements in physical problems, emotional problems, mental health and balance.
      TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number
      ISRCTN53367487, information available in http://www.controlled
      trials.com/ISRCTN53367487.

PMID- 19605375
TI  - Distinct mesenchymal progenitor cell subsets in the adult human synovium.
AB  - OBJECTIVE: To analyse the heterogeneity at the single-cell level of human
      mesenchymal progenitor cells from SM. METHODS: Cell populations were
      enzymatically released from the knee joint synovium of adult human individuals.
      Single cell-derived clonal populations were obtained by limiting dilution and
      serially passaged to determine growth rates. Phenotypic analysis was carried out
      by flow cytometry. Replicative senescence was assessed by the senescence
      associated beta-galactosidase staining. Telomere lengths were determined
      semiquantitatively by Southern blotting. Telomerase activity was measured using a
      real-time quantitative telomerase repeat amplification procedure. Culture
      expanded clonal populations were subjected to in vitro differentiation assays to
      investigate their mesenchymal multipotency. RESULTS: The 50 clones analysed
      displayed wide variations in the proliferation rates, even within the same donor
      sample. The time taken to reach 20 population doublings ranged from 44 to 130
      days. The phenotype of the clones tested was compatible with that of mesenchymal
      stem cells. Mean telomere lengths ranged from 5.2 to 10.9 kb with positive linear
      trend with telomerase activity, but no correlation with proliferative rates or
      cell senescence. All clones tested were capable of chondrogenic and osteogenic
      differentiation, though with large variability in potency. In contrast, only 30%
      of the clones were adipogenic. CONCLUSIONS: We report for the first time the co
      existence, within the synovium, of progenitor cell subsets with distinct
      mesenchymal differentiation potency. Our findings further emphasize the need for
      strategies to purify cell populations with the clinically desired tissue
      formation potentials.

PMID- 19605376
TI  - Effect of recombinant activated factor VII in critical bleeding: clinical
      experience of a single center.
AB  - Recombinant activated factor VII (rFVIIa) has been successfully used ''off
      label'' in patients with refractory life-threatening hemorrhage. Intravenous
      rFVIIa was given to 31 patients unresponsive to standard therapy with blood
      products and surgical reexploration, who were bleeding due to trauma, surgery,
      organ transplantation, liver cirrhosis, ruptured uterus. We recorded their
      coagulation and hematologic profiles, acid-base balance, blood loss, number of
      red blood cells (RBC), plasma and platelet transfusions, complications, and
      survival. rFVIIa (mean dose 132.2 +/- 56.3 microg/kg) effectively contained the
      hemorrhage in 28/31 (90.3%) cases, with a mean reduction in blood loss from 12.4
      +/- 10.2 to 2.7 +/- 2.2 L (P < .0001). The need for RBC, platelet, and plasma
      transfusion decreased significantly after rFVIIa, with a consequent significant
      improvement in clotting of test hematocrit, pH, and bicarbonates. Four patients
      had adverse events potentially related to rFVIIa. The survival rates after 1 and
      30 days were 48.4% and 29.1%, respectively.

PMID- 19605377
TI  - Increased thrombophilic tendency in pediatric cystic fibrosis patients.
AB  - Thrombophilia has recently been reported to be increased in patients with cystic
      fibrosis (CF). We wanted to determine whether this was applicable to our
      population with CF and how our patients compared to the previously reported
      groups. Seventy one pediatric CF patients were assessed for a thrombophilic
      tendency, using a lupus anticoagulant screen, protein C, protein S, antithrombin
      assay, and activated protein C resistance (APCR) screen. The incidence of
      activate protein C resistance (4.2%) was within expected limits for the general
      population as was the incidence of antithrombin deficiency. However there was a
      marked increase in the incidence of lupus anticoagulants (18%) and 14% and 19.7%
      of the patients showed a reduced protein C and protein S, respectively, far in
      excess of the general population. This increased incidence of thrombophilia was
      not related to any specific CF phenotype and while perturbed liver function
      cannot be entirely ruled out, it appeared unlikely to be responsible for all the
      abnormal coagulation findings. Despite the apparent thrombophilic tendency, no
      clinically evident thrombotic episodes were noted during the study period.
      Thrombophilia is of concern because of the increasingly frequent placement of
      indwelling catheters in CF patients. The precise cause for the thrombophilic
      tendency in CF patients is unknown at this stage.

PMID- 19605378
TI  - Oral systemic administration of Ankaferd blood stopper has no short-term toxicity
      in an in vivo rabbit experimental model.
AB  - BACKGROUND: Ankaferd blood stopper (ABS) is a standardized herbal extract
      obtained from 5 different plants. In Turkey, it has been approved for local
      topical applications in external postsurgical and postdental surgery bleedings.
      Ankaferd blood stopper, besides its hemostatic activity, has in vitro anti
      infectious and antineoplastic actions. OBJECTIVE: The aim of this study was to
      assess short-term hematological and biochemical safety following the oral
      systemic administration of ABS to rabbits. METHODS: Twelve rabbits (aged 6-12
      months) were included to test the safety of oral ABS. Animals were divided into 4
      groups, which had ABS administered orally at doses of 1, 3, 6, and 9 mL,
      irrespective of their weight. The general well-being and feeding patterns of the
      animals were observed for a period of 7 days. Blood samples (5.5 mL) were
      obtained just before oral administration, on days 1 and 4. RESULTS: During the
      observation period of 7 days, none of the animals showed any abnormal behavior or
      deviation from the normal. Acute mucosal toxicity, hematotoxicity,
      hepatotoxicity, nephrotoxicity, and biochemical toxicity were not observed during
      the short-term follow-up of the animals. CONCLUSIONS: No signs of toxicity were
      observed in rabbits during short-term study with oral ABS administration.

PMID- 19605379
TI  - Predictors of condom use among Israeli soldiers.
AB  - Only a small percentage of young people aged 18 to 20 years use condoms
      regularly. Thus, the younger population has an increased risk of contracting
      sexually transmitted diseases. This study examines the underlying determinants of
      condom use among soldiers based on the theory of planned behavior as well as the
      influence of soldiers' social circumstances and prior sexual experience. A
      correlational design using an exploratory survey method was used. Participants
      were sampled in a convenience sample of 113 male soldiers from the Israel defense
      forces. A total of 70.1% of soldiers use condoms in their first sexual
      experience, however, this percentage subsequently decreases. The study indicates
      that soldiers are not familiar with the risks of frequent oral and anal sex.
      Behavioral intentions and self-control are significant predictors of condom use.
      Condom use among soldiers from one-parent families was lower than among soldiers
      from two-parent families. The theory of planned behavior seems to be a helpful
      method of predicting condom use among soldiers. Accordingly, efforts should be
      channeled at attempts to generate changes in soldiers' views of condom use,
      intensifying normative pressures operated by their social milieu, and increasing
      their self-control in the use of condoms.

PMID- 19605380
TI  - The design and development of the father-child instrument (FCI) for assessing the
      characteristics of fathers' availability and engagement with their preschool
      children.
AB  - Despite the fact that father-child involvement has extensive effects on the
      health and well-being of the family, there is a paucity of research on fathers'
      presence in health care research. The design and development of an instrument for
      assessing the characteristics of fathers' availability and engagement with their
      preschool-aged children in Finland is presented. Data collection was undertaken
      in two separate periods involving 263 and 821 fathers. Results indicate that the
      father-child instrument (FCI) is ready for use in research seeking to assess
      fathers' availability and engagement with their preschoolers. Further research is
      nonetheless required to assess the potential for a more sensitive interaction and
      for the generalization of the FCI.

PMID- 19605374
TI  - Hip involvement in ankylosing spondylitis: epidemiology and risk factors
      associated with hip replacement surgery.
AB  - OBJECTIVES: Although clinicians recognize hip involvement, which frequently leads
      to hip replacement surgery, as an important feature of AS, data on the
      epidemiology, nature of the disease and therapeutic strategies are scarce. We
      aimed to describe the epidemiology of clinical and radiological hip involvement
      and define the risk factors for the hip replacement surgery in AS patients.
      METHODS: Data from 3 datasets were merged, including 847 Belgian (ASPECT
      database), 1405 Spanish (REGISPONSER database) and 466 Ibero-American (RESPONDIA
      database) AS patients. The ASPECT and REGISPONSER database (Dataset A) are used
      for exploratory analysis; the RESPONDIA database (Dataset B) is used for
      confirmative analysis. Factors associated with hip involvement and the hip
      replacement surgery were analysed. RESULTS: Twenty four (REGISPONSER) to 36%
      (RESPONDIA) of AS patients under rheumatologist's care presented clinical hip
      involvement, including the 5% (Dataset A) of AS patients who needed hip
      replacement surgery. Patients with hip involvement had significantly worse
      overall Bath Ankylosing Spondylitis Functional Index (BASFI) scores compared with
      patients without hip involvement (mean difference = 1.6, P < 0.001) (Dataset A,
      confirmed in B). Corrected for disease duration, patients with early disease
      onset, enthesial and axial disease needed most frequently hip replacement surgery
      (Dataset A, confirmed in B). CONCLUSION: Hip involvement is commonly recognized
      by rheumatologists in AS patients, and involves about one out of the three to
      four patients with AS and is associated with impaired functioning reflected by
      higher overall BASFI scores. Early onset of disease, axial and enthesial disease
      are associated with the hip replacement surgery in AS.

PMID- 19605381
TI  - Stress, song and survival in sparrows.
AB  - The stress response--increases in circulating glucocorticoids following a
      stressor--is typically considered adaptive, but few studies address the fitness
      consequences of individual variation in stress response. Generally, due to
      negative consequences of prolonged elevation of glucocorticoids, animals should
      have a transient stress response just sufficient to cope with the stressor. In
      rodents, stress responsiveness is affected by early developmental experience, and
      hyper-responsiveness to stress is linked to morbidity and mortality. We assessed
      individual variation in stress responses in free-living song sparrows, Melospiza
      melodia, in relation to fitness-related measures including song and overwinter
      survival. Birds with greater increases in corticosterone 30 min following
      restraint stress were less likely to return to breed the following year. Stress
      responsiveness was also correlated with song complexity: males with fewer
      syllables in their song repertoires had greater stress reactivity. Our findings
      support the hypothesis that developmental stressors both impair song development
      and affect the adult stress response. Thus, individual variation in the stress
      response may relate to variation in fitness.

PMID- 19605382
TI  - Ecology, evolution and genetics join together on Canada's east coast.
AB  - The 4th regular meeting of the Canadian Society of Ecology and Evolution was held
      in conjunction with the 52nd Annual Conference of the Genetics Society of Canada
      at Dalhousie University, Halifax, from 14 to 17 May 2009.

PMID- 19605383
TI  - Western scrub-jays conceal auditory information when competitors can hear but
      cannot see.
AB  - Western scrub-jays (Aphelocoma californica) engage in a variety of cache
      protection strategies to reduce the chances of cache theft by conspecifics. Many
      of these strategies revolve around reducing visual information to potential
      thieves. This study aimed to determine whether the jays also reduce auditory
      information during caching. Each jay was given the opportunity to cache food in
      two trays, one of which was filled with small pebbles that made considerable
      noise when cached in ('noisy' tray), whereas the other one contained soil that
      made little detectable noise when cached in ('quiet' tray). When the jays could
      be heard, but not seen, by a competitor, they cached proportionally less food
      items in the 'noisy' substrate than when they cached alone in the room, or when
      they could be seen and heard by competitors. These results suggest that western
      scrub-jays know when to conceal auditory information, namely when a competitor
      cannot see but can hear the caching event.

PMID- 19605384
TI  - The evolution of growth rates on an expanding range edge.
AB  - Individuals in the vanguard of a species invasion face altered selective
      conditions when compared with conspecifics behind the invasion front. Assortment
      by dispersal ability on the expanding front, for example, drives the evolution of
      increased dispersal, which, in turn, leads to accelerated rates of invasion. Here
      I propose an additional evolutionary mechanism to explain accelerating invasions:
      shifts in population growth rate (r). Because individuals in the vanguard face
      lower population density than those in established populations, they should
      (relative to individuals in established populations) experience greater r
      selection. To test this possibility, I used the ongoing invasion of cane toads
      (Bufo marinus) across northern Australia. Life-history theory shows that the most
      efficient way to increase the rate of population growth is to reproduce earlier.
      Thus, I predict that toads on the invasion front will exhibit faster individual
      growth rates (and thus will reach breeding size earlier) than those from older
      populations. Using a common garden design, I show that this is indeed the case:
      both tadpoles and juvenile toads from frontal populations grow around 30 per cent
      faster than those from older, long established populations. These results support
      theoretical predictions that r increases during range advance and highlight the
      importance of understanding the evolution of life history during range advance.

PMID- 19605385
TI  - Accessory male investment can undermine the evolutionary stability of
      simultaneous hermaphroditism.
AB  - Sex allocation (SA) models are traditionally based on the implicit assumption
      that hermaphroditism must meet criteria that make it stable against transition to
      dioecy. This, however, puts serious constraints on the adaptive values that SA
      can attain. A transition to gonochorism may, however, be impossible in many
      systems and therefore realized SA in hermaphrodites may not be limited by
      conditions that guarantee stability against dioecy. We here relax these
      conditions and explore how sexual selection on male accessory investments (e.g. a
      penis) that offer a paternity benefit affects the evolutionary stable strategy SA
      in outcrossing, simultaneous hermaphrodites. Across much of the parameter space,
      our model predicts male allocations well above 50 per cent. These predictions can
      help to explain apparently 'maladaptive' hermaphrodite systems.

PMID- 19605386
TI  - Sexual conflict, sex allocation and the genetic system.
AB  - Decisions over what sex ratio to produce can have far-reaching evolutionary
      consequences, for both offspring and parents. However, the extent to which males
      and females come into evolutionary conflict over aspects of sex allocation
      depends on the genetic system: when genes are passed to the next generation
      unequally by the two sexes (as in haplodiploidy, for example), this biased
      transmission can facilitate a range of conflicts not seen in diploids. However,
      much less attention has been paid to these forms of sexual conflict, not least
      because it has not always been clear how the conflicts could be realized. Here we
      consider how biased gene transmission, as expressed in different genetic systems,
      enhances the opportunity for sex ratio conflict and give empirical examples that
      confirm that males and females have the opportunity to influence sex ratios.

PMID- 19605387
TI  - Host-parasite interactions: resist or tolerate but never stop running.
AB  - A conference exploring 'The impact of the environment on innate immunity: the
      threat of diseases' was held on 4-9 May 2009 in Obergurgl, Austria, thanks to the
      support from the European Science Foundation, Innsbruck University and the
      Austrian Science Foundation. The goals of the conference were to explore how the
      outcomes of host-parasite interactions depend on variation across individuals,
      their parasites and the environment in which they both find themselves. Central
      themes were the inherent costs of mounting an immune response, the ability of
      some organisms to pre-empt infection by 'priming' their immune systems, the fact
      that parasites learn to evade immune responses over time and the use of theory to
      predict when diseases will get out of hand. Many of the systems presented had
      clear impacts on human health, agriculture or the maintenance of complex
      ecosystems. There was common ground throughout in developing methodologies and
      embracing what one of the organizers termed the 'interactome' between hosts and
      those which would exploit them.

PMID- 19605388
TI  - 'Tales of Symphonia': extinction dynamics in response to past climate change in
      Madagascan rainforests.
AB  - Madagascar's rainforests are among the most biodiverse in the world.
      Understanding the population dynamics of important species within these forests
      in response to past climatic variability provides valuable insight into current
      and future species composition. Here, we use a population-level approach to
      analyse palaeoecological records over the last 5300 years to understand how
      populations of Symphonia cf. verrucosa became locally extinct in some rainforest
      fragments along the southeast coast of Madagascar in response to rapid climate
      change, yet persisted in others. Our results indicate that regional (climate)
      variability contributed to synchronous decline of S. cf. verrucosa populations in
      these forests. Superimposed on regional fluctuations were local processes that
      could have contributed or mitigated extinction. Specifically, in the forest with
      low soil nutrients, population model predictions indicated that there was
      coexistence between S. cf. verrucosa and Erica spp., but in the nutrient-rich
      forest, interspecific effects between Symphonia and Erica spp. may have pushed
      Symphonia to extinction at the peak of climatic change. We also demonstrate that
      Symphonia is a good indicator of a threshold event, exhibiting erratic
      fluctuations prior to and long after the critical climatic point has passed.

PMID- 19605389
TI  - A distinct infection cost associated with trans-generational priming of
      antibacterial immunity in bumble-bees.
AB  - The adaptive value of facultative maternal adjustment of offspring immunity, or
      trans-generational immune-priming, will depend on the ecological background. In
      particular, where there is a mismatch between the immune adjustment and offspring
      environment, the immunological link between mothers and offspring may be
      disadvantageous owing to the presence of associated costs. Costs to an individual
      of responding to an immune challenge are extensively documented. However, in
      addition to parents, the relevant costs for trans-generational immune-priming
      also pertain to offspring, but as yet it is unknown what costs offspring will
      bear. In bumble-bees, higher antibacterial activity has been shown as a trans
      generational effect when mothers receive a bacterial-based immune challenge prior
      to colony founding. Here we show that while naive offspring from immune
      challenged mothers do not show evidence for a direct energy-related survival
      cost, they do show increased susceptibility to a parasite distinctly unrelated to
      the maternal challenge. The presence of costs associated with trans-generational
      immune-priming will shape the evolution of this trait depending on the ecological
      setting.

PMID- 19605391
TI  - Historical distribution patterns of trigonioidids (non-marine Cretaceous
      bivalves) in Asia and their palaeogeographic significance.
AB  - The non-marine trigonioidid bivalves show five phases of radiation in the
      Cretaceous of Pal-Asia: pre-Aptian (?Valanginian/Hauterivian-Barremian), Aptian,
      Albian, Cenomanian and Turonian-Maastrichtian. Their distribution patterns show
      two distinct palaeo-river systems feeding trigonioidids. Before the Cenomanian,
      the river system occupied the southwestern-southern-southeastern Pal-Asian
      continental margin areas. During the Turonian-Maastrichtian, it extended along
      the line of southcentral China-eastern China-northeastern China-northern China
      and Mongolia-northwestern China-eastern Fergana Basin of Kyrgyzstan-western
      Tajikistan Basin of Tajikistan-Tashkent area of Kazakhstan-central Kyzylkum of
      northern Uzbekistan-Aral Sea area of Kazakhstan. Furthermore, the general
      trigonioidid distribution pattern demonstrates that Japan was probably attached
      to part of eastern China and/or Korea during the ?Valanginian/Hauterivian
      Cenomanian stages.

PMID- 19605390
TI  - Strategic (adaptive) hypothermia in bull dromedary camels during rut; could it
      increase reproductive success?
AB  - In this study of body temperatures (T(b)) in free ranging dromedary camels, we
      found that bulls in rut start the days cooler. Daily minima during rut averaged
      0.6 degrees C lower than at other times (95% CI 0.27-0.94 degrees C) and daily
      maxima averaged 0.45 degrees C higher (95% CI -0.01 to -0.91 degrees C),
      increasing the daily T(b) cycle. Knut Schmidt-Nielsen described a similar pattern
      in captive dromedaries deprived of water in hot conditions, which he interpreted
      as a strategy to conserve water. Our observations were made in winter and with
      water freely available. Dromedaries can apparently employ heterothermy for more
      than just water conservation. In the strenuous daily contests between rival bulls
      in rut, a lower T(b) early in the day should extend the time for which a
      contestant can challenge or defend before heat stress becomes a problem.
      Calculations show that lowering T(b) by even 0.6 degrees C extends that time by
      more than 30 min, and many daily minima during rut were lower than that. Because
      the eventual winner of contests gains or retains a herd of females, we speculate
      that cooler T(b) at the start of daily contests confers an advantage which
      translates directly into increased reproductive success.

PMID- 19605392
TI  - Towards a systems biology approach to understanding seed dormancy and
      germination.
AB  - Seed germination is the first adaptive decision in the development of many land
      plants. Advances in genetics and molecular physiology have taught us much about
      the control of germination using the model plant Arabidopsis thaliana. Here we
      review the current state of the art with an emphasis on mechanistic
      considerations and explore the potential impact of a systems biology approach to
      the problem.

PMID- 19605394
TI  - Hookworm infection, anaemia and genetic variability of the New Zealand sea lion.
AB  - Hookworms are intestinal blood-feeding nematodes that parasitize and cause high
      levels of mortality in a wide range of mammals, including otariid pinnipeds.
      Recently, an empirical study showed that inbreeding (assessed by individual
      measures of multi-locus heterozygosity) is associated with hookworm-related
      mortality of California sea lions. If inbreeding increases susceptibility to
      hookworms, effects would expectedly be stronger in small, fragmented populations.
      We tested this assumption in the New Zealand sea lion, a threatened otariid that
      has low levels of genetic variability and high hookworm infection rates. Using a
      panel of 22 microsatellites, we found that average allelic diversity (5.9) and
      mean heterozygosity (0.72) were higher than expected for a small population with
      restricted breeding, and we found no evidence of an association between genetic
      variability and hookworm resistance. However, similar to what was observed for
      the California sea lion, homozygosity at a single locus explained the occurrence
      of anaemia and thrombocytopenia in hookworm-infected pups (generalized linear
      model, F = 11.81, p < 0.001) and the effect was apparently driven by a particular
      allele (odds ratio = 34.95%; CI: 7.12-162.41; p < 0.00001). Our study offers
      further evidence that these haematophagus parasites exert selective pressure on
      otariid blood-clotting processes.

PMID- 19605393
TI  - Viscous medium promotes cooperation in the pathogenic bacterium Pseudomonas
      aeruginosa.
AB  - There has been extensive theoretical debate over whether population viscosity
      (limited dispersal) can favour cooperation. While limited dispersal increases the
      probability of interactions occurring between relatives, which can favour
      cooperation, it can also lead to an increase in competition between relatives and
      this can reduce or completely negate selection for cooperation. Despite much
      theoretical attention, there is a lack of empirical research investigating these
      issues. We cultured Pseudomonas aeruginosa bacteria in medium with different
      degrees of viscosity and examined the fitness consequences for a cooperative
      trait-the production of iron-scavenging siderophore molecules. We found that
      increasing viscosity of the growth medium (i) significantly limited bacterial
      dispersal and the diffusion of siderophore molecules and (ii) increased the
      fitness of individuals that produced siderophores relative to mutants that did
      not. We propose that viscosity favours siderophore-producing individuals in this
      system, because the benefits of siderophore production are more likely to accrue
      to relatives (i.e. greater indirect benefits), and, at the same time, bacteria
      are more likely to gain direct fitness benefits by taking up siderophore
      molecules produced by themselves (i.e. the trait becomes less cooperative). Our
      results suggest that viscosity of the microbial growth environment is a crucial
      factor determining the dynamics of wild-type bacteria and siderophore-deficient
      mutants in natural habitats, such as the viscous mucus in cystic fibrosis lung.

PMID- 19605395
TI  - Collective decision-making in white-faced capuchin monkeys.
AB  - In group-living animals, collective movements are a widespread phenomenon and
      occur through consensus decision. When one animal proposes a direction for group
      movement, the others decide to follow or not and hence take part in the decision
      making process. This paper examines the temporal spread of individual responses
      after the departure of a first individual (the initiator) in a semi-free ranging
      group of white-faced capuchins (Cebus capucinus). We analysed 294 start attempts,
      111 succeeding and 183 failing. Using a modelling approach, we have demonstrated
      that consensus decision-making for group movements is based on two complementary
      phenomena in this species: firstly, the joining together of group members thanks
      to a mimetic process; and secondly, a modulation of this phenomenon through the
      propensity of the initiator to give up (i.e. cancellation rate). This
      cancellation rate seems to be directly dependent upon the number of followers:
      the greater this number is, the lower the cancellation rate is seen to be. The
      coupling between joining and cancellation rates leads to a quorum: when three
      individuals join the initiator, the group collectively moves. If the initiator
      abandons the movement, this influences the joining behaviour of the other group
      members, which in return influences the initiator's behaviour. This study
      demonstrates the synergy between the initiator's behaviour and the self-organized
      mechanisms underlying group movements.

PMID- 19605396
TI  - A new North American therizinosaurid and the role of herbivory in 'predatory'
      dinosaur evolution.
AB  - Historically, ecomorphological inferences regarding theropod (i.e. 'predatory')
      dinosaurs were guided by an assumption that they were singularly
      hypercarnivorous. A recent plethora of maniraptoran discoveries has produced
      evidence challenging this notion. Here, we report on a new species of
      maniraptoran theropod, Nothronychus graffami sp. nov. Relative completeness of
      this specimen permits a phylogenetic reassessment of Therizinosauria-the theropod
      clade exhibiting the most substantial anatomical evidence of herbivory. In the
      most comprehensive phylogenetic study of the clade conducted to date, we recover
      Therizinosauria as the basalmost maniraptoran lineage. Using concentrated changes
      tests, we present evidence for correlated character evolution among herbivorous
      and hypercarnivorous taxa and propose ecomorphological indicators for future
      interpretations of diet among maniraptoran clades. Maximum parsimony
      optimizations of character evolution within our study indicate an ancestral
      origin for dietary plasticity and facultative herbivory (omnivory) within the
      clade. These findings suggest that hypercarnivory in paravian dinosaurs is a
      secondarily derived dietary specialization and provide a potential mechanism for
      the invasion of novel morpho- and ecospace early in coelurosaurian evolution-the
      loss of obligate carnivory and origin of dietary opportunism.

PMID- 19605397
TI  - Does stress response predict return rate in a migratory bird species? A study of
      American redstarts and their non-breeding habitat.
AB  - In vertebrates, the adrenocortical stress response activates an emergency life
      history stage, which is thought to promote survival by helping individuals escape
      life-threatening situations. Although the adrenocortical stress response promotes
      many behavioural and physiological changes, it remains unclear whether this
      stress response actually translates into higher survival in wild vertebrates. We
      measured the adrenocortical stress response of non-breeding American redstarts
      (Setophaga ruticilla), a migratory bird that wintered in habitats of either high
      (mangroves) or low suitability (scrubs), and subsequently monitored their return
      rate during the following non-breeding seasons. The intensity of the
      adrenocortical stress response was consistent within individuals across the non
      breeding season and was positively correlated with return rates in redstarts that
      wintered in scrubs, but not in redstarts that wintered in mangroves. Thus, in a
      context-dependent manner, the ability of an individual to physiologically react
      to stress determines its ability of returning to its non-breeding territory the
      following winters. For an individual, the ability to mount an important
      adrenocortical stress response probably benefits to survival. However, this
      beneficial effect probably depends on an individual's environment and phenotypic
      characteristics because these two variables are likely to affect its probability
      of being confronted with life-threatening stressors during its annual life cycle.

PMID- 19605398
TI  - Developmental basis for telencephalon expansion in waterfowl: enlargement prior
      to neurogenesis.
AB  - Some altricial and some precocial species of birds have evolved enlarged
      telencephalons compared with other birds. Previous work has shown that finches
      and parakeets, two species that hatch in an immature (i.e. altricial) state,
      enlarged their telencephalon by delaying telencephalic neurogenesis. To determine
      whether species that hatch in a relatively mature (i.e. precocial) state also
      enlarged their telencephalon by delaying telencephalic neurogenesis, we examined
      brain development in geese, ducks, turkeys and chickens, which are all precocial.
      Whereas the telencephalon occupies less than 55 per cent of the brain in chickens
      and turkeys, it occupies more than 65 per cent in ducks and geese. To determine
      how these species differences in adult brain region proportions arise during
      development, we examined brain maturation (i.e. neurogenesis timing) and
      estimated telencephalon, tectum and medulla volumes from serial Nissl-stained
      sections in the four species. We found that incubation time predicts the timing
      of neurogenesis in all major brain regions and that the telencephalon is
      proportionally larger in ducks and geese before telencephalic neurogenesis
      begins. These findings demonstrate that the expansion of the telencephalon in
      ducks and geese is achieved by altering development prior to neurogenesis onset.
      Thus, precocial and altricial species evolved different developmental strategies
      to expand their telencephalon.

PMID- 19605399
TI  - Where sociality and relatedness diverge: the genetic basis for hierarchical
      social organization in African elephants.
AB  - Hierarchical properties characterize elephant fission-fusion social organization
      whereby stable groups of individuals coalesce into higher order groups or split
      in a predictable manner. This hierarchical complexity is rare among animals and,
      as such, an examination of the factors driving its emergence offers unique
      insight into the evolution of social behaviour. Investigation of the genetic
      basis for such social affiliation demonstrates that while the majority of core
      social groups (second-tier affiliates) are significantly related, this is not
      exclusively the case. As such, direct benefits received through membership of
      these groups appear to be salient to their formation and maintenance. Further
      analysis revealed that the majority of groups in the two higher social echelons
      (third and fourth tiers) are typically not significantly related. The majority of
      third-tier members are matrilocal, carrying the same mtDNA control region
      haplotype, while matrilocality among fourth-tier groups was slightly less than
      expected at random. Comparison of results to those from a less disturbed
      population suggests that human depredation, leading to social disruption, altered
      the genetic underpinning of social relations in the study population. These
      results suggest that inclusive fitness benefits may crystallize elephant
      hierarchical social structuring along genetic lines when populations are
      undisturbed. However, indirect benefits are not critical to the formation and
      maintenance of second-, third- or fourth-tier level bonds, indicating the
      importance of direct benefits in the emergence of complex, hierarchical social
      relations among elephants. Future directions and conservation implications are
      discussed.

PMID- 19605400
TI  - On spatially explicit models of cholera epidemics.
AB  - We generalize a recently proposed model for cholera epidemics that accounts for
      local communities of susceptibles and infectives in a spatially explicit
      arrangement of nodes linked by networks having different topologies. The vehicle
      of infection (Vibrio cholerae) is transported through the network links that are
      thought of as hydrological connections among susceptible communities. The
      mathematical tools used are borrowed from general schemes of reactive transport
      on river networks acting as the environmental matrix for the circulation and
      mixing of waterborne pathogens. Using the diffusion approximation, we
      analytically derive the speed of propagation for travelling fronts of epidemics
      on regular lattices (either one-dimensional or two-dimensional) endowed with
      uniform population density. Power laws are found that relate the propagation
      speed to the diffusion coefficient and the basic reproduction number. We
      numerically obtain the related, slower speed of epidemic spreading for more
      complex, yet realistic river structures such as Peano networks and optimal
      channel networks. The analysis of the limit case of uniformly distributed
      population sizes proves instrumental in establishing the overall conditions for
      the relevance of spatially explicit models. To that extent, the ratio between
      spreading and disease outbreak time scales proves the crucial parameter. The
      relevance of our results lies in the major differences potentially arising
      between the predictions of spatially explicit models and traditional
      compartmental models of the susceptible-infected-recovered (SIR)-like type. Our
      results suggest that in many cases of real-life epidemiological interest, time
      scales of disease dynamics may trigger outbreaks that significantly depart from
      the predictions of compartmental models.

PMID- 19605401
TI  - Calcium ions induce collapse of charged O-side chains of lipopolysaccharides from
      Pseudomonas aeruginosa.
AB  - Lipopolysaccharide (LPS) monolayers deposited on planar, hydrophobic substrates
      were used as a defined model of outer membranes of Pseudomonas aeruginosa strain
      dps 89. To investigate the influence of ions on the (out-of-plane) monolayer
      structure, we measured specular X-ray reflectivity at high energy (22 keV) to
      ensure transmission through water. Electron density profiles were reconstructed
      from the reflectivity curves, and they indicate that the presence of Ca(2+) ions
      induces a significant change in the conformation of the charged polysaccharide
      head groups (O-side chains). Monte Carlo simulations based on a minimal computer
      model of LPS molecules allow for the modelling of 100 or more molecules over 10(
      3) s and theoretically explained the tendency found by experiments.

PMID- 19605402
TI  - Constrained solution scattering modelling of human antibodies and complement
      proteins reveals novel biological insights.
AB  - X-ray and neutron-scattering techniques characterize proteins in solution and
      complement high-resolution structural studies. They are useful when either a
      large protein cannot be crystallized, in which case scattering yields a solution
      structure, or a crystal structure has been determined and requires validation in
      solution. These solution structures are determined by the application of
      constrained modelling methods based on known subunit structures. First, an
      appropriate starting model is generated. Next, its conformation is randomized to
      generate thousands of models for trial-and-error fits. Comparison with the
      experimental data identifies a small family of best-fit models. Finally, their
      significance for biological function is assessed. We illustrate this in
      application to structure determinations for secretory immunoglobulin A, the most
      prevalent antibody in the human body and a first line of defence in mucosal
      immunity. We also discuss the applications to the large multi-domain proteins of
      the complement system, most notably its major regulator factor H, which is
      important in age-related macular degeneration and renal diseases. We discuss the
      importance of complementary data from analytical ultracentrifugation, and
      structural studies of protein-protein complexes. We conclude that constrained
      scattering modelling makes useful contributions to our understanding of antibody
      and complement structure and function.

PMID- 19605403
TI  - Bio-metals imaging and speciation in cells using proton and synchrotron radiation
      X-ray microspectroscopy.
AB  - The direct detection of biologically relevant metals in single cells and of their
      speciation is a challenging task that requires sophisticated analytical
      developments. The aim of this article is to present the recent achievements in
      the field of cellular chemical element imaging, and direct speciation analysis,
      using proton and synchrotron radiation X-ray micro- and nano-analysis. The recent
      improvements in focusing optics for MeV-accelerated particles and keV X-rays
      allow application to chemical element analysis in subcellular compartments. The
      imaging and quantification of trace elements in single cells can be obtained
      using particle-induced X-ray emission (PIXE). The combination of PIXE with
      backscattering spectrometry and scanning transmission ion microscopy provides a
      high accuracy in elemental quantification of cellular organelles. On the other
      hand, synchrotron radiation X-ray fluorescence provides chemical element imaging
      with less than 100 nm spatial resolution. Moreover, synchrotron radiation offers
      the unique capability of spatially resolved chemical speciation using micro-X-ray
      absorption spectroscopy. The potential of these methods in biomedical
      investigations will be illustrated with examples of application in the fields of
      cellular toxicology, and pharmacology, bio-metals and metal-based nano-particles.

PMID- 19605404
TI  - High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate
      with metastatic disease in patients with pediatric solid malignancies.
AB  - PURPOSE: Pediatric solid malignancies display important angiogenic potential, and
      blocking tumor angiogenesis represents a new therapeutic approach for these
      patients. Recent studies have evidenced rare circulating cells with endothelial
      features contributing to tumor neovascularization and have shown the pivotal role
      of bone marrow-derived (BMD) progenitor cells in metastatic disease progression.
      We measured these cells in patients with pediatric solid malignancies as a
      prerequisite to clinical trials with antiangiogenic therapy. PATIENTS AND
      METHODS: Peripheral blood was drawn from 45 patients with localized (n = 23) or
      metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating
      vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells,
      defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events,
      were measured in progenitor-enriched fractions by flow cytometry. Mature
      circulating endothelial cells (CEC) were measured in whole blood as
      CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2
      plasma levels. RESULTS: The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented
      <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the
      median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in
      patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of
      circulating BMD progenitors (P < 0.0001), and differed significantly between
      patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%
      10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7
      cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD
      progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease
      status. CONCLUSION: High levels of circulating VEGFR2+-BMD progenitor cells
      correlated with metastatic disease. Our study provides novel insights for
      angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic
      targeting of VEGFR2+-BMD progenitors could be of interest.

PMID- 19605406
TI  - Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and
      potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells.
AB  - Pancreatic cancer is an aggressive malignancy that is generally refractory to
      chemotherapy, thus posing experimental and clinical challenges. In this study,
      the antiproliferative effect of the triterpenoid compound cucurbitacin B was
      tested in vitro and in vivo against human pancreatic cancer cells. Dose-response
      studies showed that the drug inhibited 50% growth of seven pancreatic cancer cell
      lines at 10(-7) mol/L, whereas clonogenic growth was significantly inhibited at 5
      x 10(-8) mol/L. Cucurbitacin B caused dose- and time-dependent G(2)-M-phase
      arrest and apoptosis of pancreatic cancer cells. This was associated with
      inhibition of activated JAK2, STAT3, and STAT5, increased level of p21(WAF1) even
      in cells with nonfunctional p53, and decrease of expression of cyclin A, cyclin
      B1, and Bcl-XL with subsequent activation of the caspase cascade. Interestingly,
      the combination of cucurbitacin B and gemcitabine synergistically potentiated the
      antiproliferative effects of gemcitabine on pancreatic cancer cells. Moreover,
      cucurbitacin B decreased the volume of pancreatic tumor xenografts in athymic
      nude mice by 69.2% (P < 0.01) compared with controls without noticeable drug
      toxicities. In vivo activation of JAK2/STAT3 was inhibited and expression of Bcl
      XL was decreased, whereas caspase-3 and caspase-9 were up-regulated in tumors of
      drug-treated mice. In conclusion, we showed for the first time that cucurbitacin
      B has profound in vitro and in vivo antiproliferative effects against human
      pancreatic cancer cells, and the compound may potentate the antiproliferative
      effect of the chemotherapeutic agent gemcitabine. Further clinical studies are
      necessary to confirm our findings in patients with pancreatic cancer.

PMID- 19605405
TI  - The cell fate determination factor DACH1 is expressed in estrogen receptor-alpha
      positive breast cancer and represses estrogen receptor-alpha signaling.
AB  - The Dachshund (dac) gene, initially cloned as a dominant inhibitor of the
      Drosophila hyperactive EGFR mutant ellipse, encodes a key component of the cell
      fate determination pathway involved in Drosophila eye development. Analysis of
      more than 2,200 breast cancer samples showed improved survival by some 40 months
      in patients whose tumors expressed DACH1. Herein, DACH1 and estrogen receptor
      alpha (ERalpha) expressions were inversely correlated in human breast cancer.
      DACH1 bound and inhibited ERalpha function. Nuclear DACH1 expression inhibited
      estradiol (E(2))-induced DNA synthesis and cellular proliferation. DACH1 bound
      ERalpha in immunoprecipitation-Western blotting, associated with ERalpha in
      chromatin immunoprecipitation, and inhibited ERalpha transcriptional activity,
      requiring a conserved DS domain. Proteomic analysis identified proline, glutamic
      acid, and leucine rich protein 1 (PELP1) as a DACH1-binding protein. The DACH1
      COOH terminus was required for binding to PELP1. DACH1 inhibited induction of
      ERalpha signaling. E(2) recruited ERalpha and disengaged corepressors from DACH1
      at an endogenous ER response element, allowing PELP1 to serve as an ERalpha
      coactivator. DACH1 expression, which is lost in poor prognosis human breast
      cancer, functions as an endogenous inhibitor of ERalpha function.

PMID- 19605408
TI  - Randomized controlled trial of intubation with the McGrath Series 5
      videolaryngoscope by inexperienced anaesthetists.
AB  - BACKGROUND: The McGrath Series 5 videolaryngoscope might reduce the incidence of
      unexpected difficult tracheal intubation. If it also performs as well as a
      standard laryngoscope during uncomplicated intubations, there would be an
      argument for the McGrath to become the laryngoscope of choice in higher risk
      settings, such as rapid sequence induction by inexperienced anaesthetists.
      Therefore, we compared the McGrath and the Macintosh laryngoscopes during routine
      tracheal intubation performed by inexperienced anaesthetists. METHODS: Single
      blind randomized controlled trial with 120 adult patients allocated to intubation
      by first-year anaesthetic trainees, using a McGrath or Macintosh laryngoscope.
      The primary outcome was time to intubation. Secondary outcomes were quality of
      view at laryngoscopy and evidence of differential learning between using the two
      laryngoscopes. A Cox proportional hazards model was used to determine the effect
      of the laryngoscopes on time to intubation. RESULTS: Duration of intubation was
      significantly longer (P<0.001) in the McGrath group [median (IQR); 47.0 (39.0
      60.0) vs 29.5 (23.0-36.8) s]. There were no significant differences in other
      outcomes, including grade of laryngoscopy view, visual confirmation of tube
      placement, number of laryngoscopies, or complications (oesophageal intubation,
      hypoxaemia, and airway trauma). There was no differential learning effect.
      CONCLUSIONS: There were no advantages to using the McGrath laryngoscope for
      uncomplicated tracheal intubation and duration of intubation was longer, so it
      should not be used as a first-line laryngoscope instrument by inexperienced
      anaesthetists.

PMID- 19605407
TI  - Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil
      requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic
      pharmacodynamic study.
AB  - BACKGROUND: There are diverse reports concerning the single-nucleotide
      polymorphism (SNP) A118G in the gene coding for the mu-opioid receptor. This
      study assessed pharmacokinetic-pharmacodynamic relationships in patients with
      acute pain (water-immersed extracorporeal shock wave lithotripsy). METHODS:
      Ninety-nine patients (ASA I-II, age 18-70) were assessed in this prospective
      observational study. Blinding was achieved by determining genotype only after the
      procedure. I.V. alfentanil was administered by patient-controlled administration
      (loading dose, 10 microg kg(-1); continuous infusion, 20 microg kg(-1) h(-1);
      bolus, 3 microg kg(-1); lockout time, 1 min); no other analgesic or sedating
      medication was used. RESULTS: The allelic frequency was 15.2% in our population.
      The G118 SNP (AG/GG) was associated with a 27% increase in plasma alfentanil
      concentration (P=0.034), a 54% increase in alfentanil dose (P=0.009), a 47%
      increase in dose per kg body weight (P=0.004), a 55% increase in dose per kg
      corrected for stimulus intensity (P=0.002), a 112% increase in the numbers of
      attempted boluses (P=0.015), a 79% increase in the numbers of successful boluses
      (P=0.013), and a 153% increase in the numbers of failed boluses (P=0.042).
      Despite the increased alfentanil self-administration, the G118 SNP was associated
      with a 52% increase in verbal analogue pain scores over the same period of time
      (P=0.047). CONCLUSIONS: We demonstrated increased opioid requirement for
      alfentanil in patients with the G118 SNP, who self-administered a higher dose,
      achieved higher plasma concentration, and yet complained of more severe pain.
      This observation suggests that G118 SNP impairs the analgesic response to
      opioids.

PMID- 19605409
TI  - Droperidol has comparable clinical efficacy against both nausea and vomiting.
AB  - BACKGROUND: Droperidol is commonly noted to be more effective at preventing
      postoperative nausea (PON) than vomiting (POV) and it is assumed to have a short
      duration of action. This may be relevant for clinical decisions, especially for
      designing multiple-drug antiemetic regimens. METHODS: We conducted a post hoc
      analysis of a large multicentre trial. Within this trial, 1734 patients underwent
      inhalation anaesthesia and were randomly stratified to receive several antiemetic
      interventions according to a factorial design, one of which was droperidol 1.25
      mg vs placebo. We considered differences to be significant when: (i) point
      estimates of one outcome are not within the limits of the confidence interval
      (CI) of the other outcome; and (ii) differences in risk ratio (also known as
      relative risks, RR) are at least 20%. RESULTS: Over 24 h, nausea was reduced from
      42.9% in the control to 32.0% in the droperidol group, corresponding to a
      relative risk (RR) of 0.75 (95% CI from 0.66 to 0.84). Vomiting was reduced from
      15.6% to 11.8%, and therefore associated with a similar RR of 0.76 (0.59-0.96).
      In the early postoperative period (0-2 h), droperidol prevented nausea and
      vomiting similarly, with an RR of 0.57 (0.46-0.69) for nausea and 0.56 (0.37
      0.85) for vomiting. In the late postoperative period (2-24 h), the RR was again
      similar with 0.83 (0.72-0.96) for nausea compared with 0.89 (0.66-1.18) for
      vomiting but significantly less compared with the early postoperative period.
      CONCLUSIONS: We conclude that droperidol prevents PON and POV equally well, yet
      its duration of action is short-lived.

PMID- 19605410
TI  - AVIDOS--a software package for European accredited aviation dosimetry.
AB  - AVIDOS is a computer code used for the dose assessment of aircraft crew exposed
      to cosmic radiation. The code employs a multiparameter model built upon
      simulations of cosmic radiation exposure done using the FLUKA Monte Carlo code.
      AVIDOS calculates both ambient dose equivalent H*(10) and effective dose E for
      flight routes over the whole world at typically used altitudes and for the full
      range of solar activity. The dose assessment procedure using AVIDOS is accredited
      by the Austrian office for accreditation according to European regulations and is
      valid in the whole Europe. AVIDOS took part in an international comparison of
      different codes assessing radiation exposure of aircraft crew where a fully
      satisfactory agreement between codes has been found. An online version of AVIDOS
      with user friendly interface is accessible to public under the internet address:
      http://avidos.healthphysics.at.

PMID- 19605412
TI  - Three human ARX mutations cause the lissencephaly-like and mental retardation
      with epilepsy-like pleiotropic phenotypes in mice.
AB  - ARX (the aristaless-related homeobox gene) is a transcription factor that
      participates in the development of GABAergic and cholinergic neurons in the
      forebrain. Many ARX mutations have been identified in X-linked lissencephaly and
      mental retardation with epilepsy, and thus ARX is considered to be a causal gene
      for the two syndromes although the neurobiological functions of each mutation
      remain unclear. We attempted to elucidate the causal relationships between
      individual ARX mutations and disease phenotypes by generating a series of mutant
      mice. We generated three types of mice with knocked-in ARX mutations associated
      with X-linked lissencephaly (P353R) and mental retardation [P353L and
      333ins(GCG)7]. Mice with the P355R mutation (equivalent to the human 353
      position) that died after birth were significantly different in Arx
      transcript/protein amounts, GABAergic and cholinergic neuronal development, brain
      morphology and lifespan from mice with P355L and 330ins(GCG)7 but considerably
      similar to Arx-deficient mice with truncated ARX mutation in lissencephaly. Mice
      with the 330ins(GCG)7 mutation showed severe seizures and impaired learning
      performance, whereas mice with the P355L mutation exhibited mild seizures and
      only slightly impaired learning performance. Both types of mutant mice exhibited
      the mutation-specific lesser presence of GABAergic and cholinergic neurons in the
      striatum, medial septum and ventral forebrain nuclei when compared with wild-type
      mice. Present findings that reveal a causal relationship between ARX mutations
      and the pleiotropic phenotype in mice, suggest that the ARX-related syndrome,
      including lissencephaly or mental retardation, is caused by only the concerned
      ARX mutations without the involvement of other genetic factors.

PMID- 19605411
TI  - DNA methylation and gene expression differences in children conceived in vitro or
      in vivo.
AB  - Epidemiological data indicate that children conceived in vitro have a greater
      relative risk of low birth-weight, major and minor birth defects, and rare
      disorders involving imprinted genes, suggesting that epigenetic changes may be
      associated with assisted reproduction. We examined DNA methylation at more than
      700 genes (1536 CpG sites) in placenta and cord blood and measured gene
      expression levels of a subset of genes that differed in methylation levels
      between children conceived in vitro versus in vivo. Our results suggest that in
      vitro conception is associated with lower mean methylation at CpG sites in
      placenta and higher mean methylation at CpG sites in cord blood. We also find
      that in vitro conception-associated DNA methylation differences are associated
      with gene expression differences at both imprinted and non-imprinted genes. The
      range of inter-individual variation in gene expression of the in vitro and in
      vivo groups overlaps substantially but some individuals from the in vitro group
      differ from the in vivo group mean by more than two standard deviations. Several
      of the genes whose expression differs between the two groups have been implicated
      in chronic metabolic disorders, such as obesity and type II diabetes. These
      findings suggest that there may be epigenetic differences in the gametes or early
      embryos derived from couples undergoing treatment for infertility. Alternatively,
      assisted reproduction technology may have an effect on global patterns of DNA
      methylation and gene expression. In either case, these differences or changes may
      affect long-term patterns of gene expression.

PMID- 19605413
TI  - Genotoxicity and morphological transformation induced by cobalt nanoparticles and
      cobalt chloride: an in vitro study in Balb/3T3 mouse fibroblasts.
AB  - Nanotechnology is an emerging field that involves the development, manufacture
      and measurement of materials and systems in the submicron to nanometer range. Its
      development is expected to have a large socio-economical impact in practically
      all fields of industrial activity. However, there is still a lack of information
      about the potential risks of manufactured nanoparticles for the environment and
      for human health. In this work, we studied the cytotoxicity, genotoxicity and
      morphological transforming activity of cobalt nanoparticles (Co-nano) and cobalt
      ions (Co(2+)) in Balb/3T3 cells. We also evaluated Co-nano dissolution in culture
      medium and cellular uptake of both Co-nano and Co(2+). Our results indicated dose
      dependent cytotoxicity, assessed by colony-forming efficiency test, for both
      compounds. The toxicity was higher for Co-nano than for Co(2) after 2 and 24 h of
      exposure, while dose-effect relationships were overlapping after 72 h.
      Statistically significant results were observed for Co-nano with the micronucleus
      test and the comet assay, while for Co(2+) positive results were observed only
      with the latter. In addition, even when Co-nano was genotoxic (at >1 microM), no
      evident dose-dependent effect was observed. Concerning morphological
      transformation, we found a statistically significant increase in the formation of
      type III foci (morphologically transformed colonies) only for Co-nano.
      Furthermore, we observed a higher cellular uptake of Co-nano compared with
      Co(2+).

PMID- 19605414
TI  - Involvement of C-22-hydroxylated brassinosteroids in auxin-induced lamina joint
      bending in rice.
AB  - The rice lamina joint is ideal material for investigating the activity of
      brassinosteroids (BRs) and auxin because of its high sensitivity to these
      compounds. Using a series of rice BR biosynthetic and receptor mutants, we
      conducted lamina joint tests to elucidate the mechanism of cross-talk between BR
      and auxin signaling in lamina joint bending. In BR biosynthetic mutants d2 and
      brd1, which are defective in C-23 hydroxylase and C-6 oxidase, respectively, the
      lamina joint response to auxin was significantly higher than that of wild-type
      plants. The other BR-biosynthetic mutants, brd2, osdwarf4 and d11, which are
      defective in C-22-hydroxylated BRs, showed less or no response to auxin. These
      results suggest that C-22-hydroxylated BRs are involved in auxin-induced lamina
      joint bending. The results were supported by the observation that inhibition of
      the hyper-response to auxin in d2 was reduced by treatment with brassinazole,
      which inhibits the function of DWARF4, the C-22 hydroxylase. In d61, which is
      defective in OsBRI1, a possible BR receptor in rice, the bending angle of the
      lamina joint in response to auxin and C-22-hydroxylated 6-deoxoBRs was nearly the
      same as that in wild-type plants. This implies that C-22-hydroxylated BRs
      function in auxin signaling independently of OsBRI1. From these observations, we
      propose that C-22-hydroxylated BRs participate in auxin signaling via a novel
      OsBRI1-independent signaling pathway.

PMID- 19605415
TI  - Identification of cis-localization elements that target glutelin RNAs to a
      specific subdomain of the cortical endoplasmic reticulum in rice endosperm cells.
AB  - Rice glutelin RNAs are localized to the cisternal endoplasmic reticulum (ER) by a
      regulated RNA transport process requiring specific cis-localization elements. We
      set out to identify these glutelin sequences by their dominant character of being
      able to re-direct the normal protein body ER localization of a maize 10 kDa delta
      zein RNA to the cisternal ER. In situ RNA localization analysis showed that the
      glutelin RNA contains multiple cis-localization elements; two located at the 5'
      and 3' ends of the coding sequences and a third located within the 3'
      untranslated region. These three regions contain two conserved sequences,
      suggesting that these RNA recognition signals may be sequence based.

PMID- 19605416
TI  - The Arabidopsis 26S proteasome subunit RPN1a is required for optimal plant growth
      and stress responses.
AB  - The current literature offers contradictory results regarding the role of the
      proteasome subunit RPN1a in Arabidopsis development. Here we show that plants
      lacking RPN1a are viable and have increased cell sizes, decreased heat shock
      tolerance, increased oxidative stress tolerance and other phenotypes
      characteristic for 26S proteasome subunit mutants. These results strengthen our
      contention that most of the phenotypes of 26S proteasome mutants in Arabidopsis
      described to date reflect a general impairment in 26S proteasome function rather
      than a specific defect of a single subunit, and suggest that the role of the
      RPN1a subunit during embryogenesis needs to be reconsidered.

PMID- 19605417
TI  - Beryllium decontamination with different solvents on different structures.
AB  - The objective of the present work was to estimate the efficiency of moistened
      wipes in removing beryllium with different solutions including Citranox, Alconox,
      NaCl 5%, Resolve, and Ledizolv on various types of surfaces such as unpainted
      metal, wood frames, painted metal, concrete, painted concrete, and Plexiglas from
      three different occupational settings. Of the three plants that were
      investigated, only surfaces in the aluminium smelter were decontaminated down to
      the clearance reference level of 0.2 microg 100 cm(-2), with all the solvents
      used. In the machine tooling and milling department, the clearance level of 0.2
      microg 100 cm(-2) was reached after the three decontaminations, with all the
      solvents. In the machine plant for the military, aerospace, and
      telecommunications industries, the beryllium concentrations on the concrete wall,
      before decontamination with the high-pressure gun, were usually >3 microg 100 cm(
      2), and concentrations as high as 31 microg 100 cm(-2) were measured. After the
      high-pressure cleanup, the beryllium concentrations were sometimes reduced by a
      factor of 10, but never reached the clearance level. Beryllium compounds that had
      adhered to most types of structures that we attempted to decontaminate were
      reduced to below the clearance reference value except on concrete floors. There
      did not seem to be any difference between the decontamination actions for all the
      solvents used in this study.

PMID- 19605418
TI  - DiProGB: the dinucleotide properties genome browser.
AB  - MOTIVATION: DiProGB is an easy to use new genome browser that encodes the primary
      nucleotide sequence by thermodynamical and geometrical dinucleotide properties.
      The nucleotide sequence is thus converted into a sequence graph. This
      visualization, supported by different graph manipulation options, facilitates
      genome analyses, because the human brain can process visual information better
      than textual information. Also, DiProGB can identify genomic regions where
      certain physical properties are more conserved than the nucleotide sequence
      itself. Most of the DiProGB tools can be applied to both, the primary nucleotide
      sequence and the sequence graph. They include motif and repeat searches as well
      as statistical analyses. DiProGB adds a new dimension to the common genome
      analysis approaches by taking into account the physical properties of DNA and
      RNA. AVAILABILITY AND IMPLEMENTATION: Source code and binaries are freely
      available for download at http://diprogb.fli-leibniz.de, implemented in C++ and
      supported on MS Windows and Linux (using e.g. WineHQ).

PMID- 19605419
TI  - Motif discovery and motif finding from genome-mapped DNase footprint data.
AB  - MOTIVATION: Footprint data is an important source of information on transcription
      factor recognition motifs. However, a footprinting fragment can contain no
      sequences similar to known protein recognition sites. Inspection of genome
      fragments nearby can help to identify missing site positions. RESULTS: Genome
      fragments containing footprints were supplied to a pipeline that constructed a
      position weight matrix (PWM) for different motif lengths and selected the optimal
      PWM. Fragments were aligned with the SeSiMCMC sampler and a new heuristic
      algorithm, Bigfoot. Footprints with missing hits were found for approximately 50%
      of factors. Adding only 2 bp on both sides of a footprinting fragment recovered
      most hits. We automatically constructed motifs for 41 Drosophila factors. New
      motifs can recognize footprints with a greater sensitivity at the same false
      positive rate than existing models. Also we discuss possible overfitting of
      constructed motifs. AVAILABILITY: Software and the collection of regulatory
      motifs are freely available at http://line.imb.ac.ru/DMMPMM.

PMID- 19605420
TI  - Probabilistic resolution of multi-mapping reads in massively parallel sequencing
      data using MuMRescueLite.
AB  - Multi-mapping sequence tags are a significant impediment to short-read sequencing
      platforms. These tags are routinely omitted from further analysis, leading to
      experimental bias and reduced coverage. Here, we present MuMRescueLite, a low
      resource requirement version of the MuMRescue software that has been used by
      several next generation sequencing projects to probabilistically reincorporate
      multi-mapping tags into mapped short read data. AVAILABILITY AND IMPLEMENTATION:
      MuMRescueLite is written in Python; executables and documentation are available
      from http://genome.gsc.riken.jp/osc/english/software/.

PMID- 19605421
TI  - Supervised prediction of drug-target interactions using bipartite local models.
AB  - MOTIVATION: In silico prediction of drug-target interactions from heterogeneous
      biological data is critical in the search for drugs for known diseases. This
      problem is currently being attacked from many different points of view, a strong
      indication of its current importance. Precisely, being able to predict new drug
      target interactions with both high precision and accuracy is the holy grail, a
      fundamental requirement for in silico methods to be useful in a biological
      setting. This, however, remains extremely challenging due to, amongst other
      things, the rarity of known drug-target interactions. RESULTS: We propose a novel
      supervised inference method to predict unknown drug-target interactions,
      represented as a bipartite graph. We use this method, known as bipartite local
      models to first predict target proteins of a given drug, then to predict drugs
      targeting a given protein. This gives two independent predictions for each
      putative drug-target interaction, which we show can be combined to give a
      definitive prediction for each interaction. We demonstrate the excellent
      performance of the proposed method in the prediction of four classes of drug
      target interaction networks involving enzymes, ion channels, G protein-coupled
      receptors (GPCRs) and nuclear receptors in human. This enables us to suggest a
      number of new potential drug-target interactions. AVAILABILITY: An implementation
      of the proposed algorithm is available upon request from the authors. Datasets
      and all prediction results are available at
      http://cbio.ensmp.fr/~yyamanishi/bipartitelocal/.

PMID- 19605423
TI  - Shift work and cancer.

PMID- 19605422
TI  - Exploring preferences for place of death with terminally ill patients:
      qualitative study of experiences of general practitioners and community nurses in
      England.
AB  - OBJECTIVE: To explore the experiences and perceptions of general practitioners
      and community nurses in discussing preferences for place of death with terminally
      ill patients. DESIGN: Qualitative study using semistructured interviews and
      thematic analysis. PARTICIPANTS: 17 general practitioners and 19 nurses (16
      district nurses, three clinical nurse specialists). SETTING: 15 general practices
      participating in the Gold Standards Framework for palliative care from three
      areas in central England with differing socio-geography. Practices were selected
      on the basis of size and level of adoption of the standards framework. RESULTS:
      All interviewees bar one had experience of discussing preferred place of death
      with terminally ill patients. They reported that preferences for place of death
      frequently changed over time and were often ill defined or poorly formed in
      patients' minds. Preferences were often described as being co-created in
      discussion with the patient or, conversely, inferred by the health professional
      without direct questioning or receiving a definitive answer from the patient.
      This inherent uncertainty challenged the practicability, usefulness, and value of
      recording a definitive preference. The extent to which the assessment of enabling
      such preferences can be used as a proxy for the effectiveness of palliative care
      delivery is also limited by this uncertainty. Generally, interviewees did not
      find discussing preferred place of death an easy area of practice, unless the
      patient broached the subject or led the discussions. CONCLUSIONS: Further
      research is needed to enable development of appropriate training and support for
      primary care professionals. Better understanding of the importance of place of
      death to patients and their carers is also needed.

PMID- 19605429
TI  - Healthcare workers should get top priority for vaccination against A/H1N1 flu,
      WHO says.

PMID- 19605430
TI  - GPs will lead UK's swine flu vaccination campaign.

PMID- 19605431
TI  - Data on flu deaths are potentially misleading, say researchers.

PMID- 19605438
TI  - Institutional safety problem. Sitting leaders ask you to stand up for safety.

PMID- 19605437
TI  - Incidental lymphocytosis. Cancer targets not as rational as testing.

PMID- 19605439
TI  - Interrogation of detainees. Physicians have been involved.

PMID- 19605440
TI  - TYM and Alzheimer's disease. More testing needed.

PMID- 19605441
TI  - TYM and Alzheimer's disease. Too many false positives.

PMID- 19605442
TI  - TYM and Alzheimer's disease. How specific is TYM?

PMID- 19605443
TI  - TYM and Alzheimer's disease. Age profile?

PMID- 19605444
TI  - TYM and Alzheimer's disease. Differentiating depression.

PMID- 19605445
TI  - TYM and Alzheimer's disease. Diagnoses can be meddlesome.

PMID- 19605449
TI  - How well are we managing the influenza A/H1N1 pandemic in the UK?

PMID- 19605450
TI  - A painful rash.

PMID- 19605454
TI  - Myocarditis mimicking Takotsubo cardiomyopathy or Takotsubo cardiomyopathy with
      secondary inflammation?

PMID- 19605456
TI  - Regional clearance of amino-terminal pro-brain natriuretic peptide from human
      plasma.
AB  - AIMS: Mechanisms for clearance of circulating amino-terminal pro-brain
      natriuretic peptide (NT-proBNP) remain poorly understood and are relevant to the
      clinical utility of NT-proBNP as a diagnostic and prognostic biomarker in
      cardiovascular disorders. We sought to determine site(s) of production and
      clearance of plasma NT-proBNP in the human circulation. METHODS AND RESULTS: In
      120 subjects undergoing clinically indicated cardiac catheterization, blood
      samples were collected from arterial and multiple venous sites to measure
      transorgan gradients of plasma NT-proBNP. Clearance of plasma NT-proBNP occurred
      across kidney, liver, musculoskeletal, and head and neck tissues. Proportions of
      calculated total body NT-proBNP clearance were 55-65% across the kidney, 20-25%
      across the liver, 10-15% across musculoskeletal tissue, and 5-10% across the head
      and neck. Renal fractional extraction of NT-proBNP was unrelated to estimated
      glomerular filtration rate. Transorgan gradients, reflecting both renal and extra
      renal NT-proBNP degradation, were correlated across multiple clearance sites
      within an individual. CONCLUSION: Plasma NT-proBNP is cleared by multiple tissues
      in the human circulation with approximately 55-65% of total clearance occurring
      in renal tissue. These data provide the first evidence for extra-glomerular
      clearance of NT-proBNP and suggest a common multisite clearance mechanism subject
      to generalized regulation. Renal NT-proBNP extraction was sustained in the face
      of even moderate levels of kidney dysfunction.

PMID- 19605458
TI  - Visible foliar injury and infrared imaging show that daylength affects short-term
      recovery after ozone stress in Trifolium subterraneum.
AB  - Tropospheric ozone is a major air pollutant affecting plants worldwide. Plants in
      northern regions can display more ozone injury than plants at lower latitudes
      despite lower ozone levels. Larger ozone influx and shorter nights have been
      suggested as possible causes. However, the effects of the dim light present
      during northern summer nights have not been investigated. Young Trifolium
      subterraneum plants kept in environmentally controlled growth rooms under long
      day (10 h bright light, 14 h dim light) or short day (10 h bright light, 14 h
      darkness) conditions were exposed to 6 h of 70 ppb ozone during daytime for three
      consecutive days. Leaves were visually inspected and imaged in vivo using thermal
      imaging before and after the daily exposure. In long-day-treated plants, visible
      foliar injury within 1 week after exposure was more severe. Multivariate
      statistical analyses showed that the leaves of ozone-exposed long-day-treated
      plants were also warmer with more homogeneous temperature distributions than
      exposed short day and control plants, suggesting reduced transpiration.
      Temperature disruptions were not restricted to areas displaying visible damage
      and occurred even in leaves with only slight visible injury. Ozone did not affect
      the leaf temperature of short-day-treated plants. As all factors influencing
      ozone influx were the same for long- and short-day-treated plants, only the dim
      nocturnal light could account for the different ozone sensitivities. Thus, the
      twilight summer nights at high latitudes may have a negative effect on repair and
      defence processes activated after ozone exposure, thereby enhancing sensitivity.

PMID- 19605457
TI  - Ripening-associated ethylene biosynthesis in tomato fruit is autocatalytically
      and developmentally regulated.
AB  - To investigate the regulatory mechanism(s) of ethylene biosynthesis in fruit,
      transgenic tomatoes with all known LeEIL genes suppressed were produced by RNA
      interference engineering. The transgenic tomato exhibited ethylene insensitivity
      phenotypes such as non-ripening and the lack of the triple response and petiole
      epinasty of seedlings even in the presence of exogenous ethylene. Transgenic
      fruit exhibited a low but consistent increase in ethylene production beyond 40
      days after anthesis (DAA), with limited LeACS2 and LeACS4 expression. 1
      Methylcyclopropene (1-MCP), a potent inhibitor of ethylene perception, failed to
      inhibit the limited increase in ethylene production and expression of the two 1
      aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) genes in the transgenic
      fruit. These results suggest that ripening-associated ethylene (system 2) in wild
      type tomato fruit consists of two parts: a small part regulated by a
      developmental factor through the ethylene-independent expression of LeACS2 and
      LeACS4 and a large part regulated by an autocatalytic system due to the ethylene
      dependent expression of the same genes. The results further suggest that basal
      ethylene (system 1) is less likely to be involved in the transition to system 2.
      Even if the effect of system 1 ethylene is eliminated, fruit can show a small
      increase in ethylene production due to unknown developmental factors. This
      increase would be enough for the stimulation of autocatalytic ethylene
      production, leading to fruit ripening.

PMID- 19605459
TI  - Characterization and application of carbohydrate-binding modules of beta-1,3
      xylanase XYL4.
AB  - beta-1,3-Xylanase from Vibrio sp. strain AX-4 (XYL4) is a modular enzyme composed
      of an N-terminal catalytic module belonging to glycoside hydrolase family 26 and
      two putative carbohydrate-binding modules (CBMs) belonging to family 31 in the C
      terminal region. To investigate the functions of these three modules, five
      deletion mutants lacking individual modules were constructed. The binding assay
      of these mutants showed that a repeating unit of the CBM was a non-catalytic beta
      1,3-xylan-binding module, while the catalytic module per se was not likely to
      contribute to the binding activity when insoluble beta-1,3-xylan was used for the
      assay. The repeating CBMs were found to specifically bind to insoluble beta-1,3
      xylan, but not to beta-1,4-xylan, Avicel, beta-1,4-mannan, curdlan, chitin or
      soluble glycol-beta-1,3-xylan. Both the enzyme and the binding activities for
      insoluble beta-1,3-xylan but not soluble glycol-beta-1,3-xylan were enhanced by
      NaCl in a concentration-dependent manner, indicating that the CBMs of XYL4 bound
      to beta-1,3-xylan through hydrophobic interaction. This property of the CBMs was
      successfully applied to the purification of a recombinant XYL4 from the cell
      extracts of Escherichia coli transformed with the xyl4 gene and the detection of
      beta-1,3-xylan-binding proteins including beta-1,3-xylanase from the extract of a
      turban shell, Turbo cornutus.

PMID- 19605460
TI  - Photocontrol of calmodulin interaction with target peptides using azobenzene
      derivative.
AB  - Calmodulin (CaM), a physiologically important Ca(2+)-binding protein,
      participates in numerous cellular regulatory processes. It is dumbbell shaped and
      contains two globular domains connected by a short alpha-helix. Each of the
      globular domains has two Ca(2+)-binding sites, the EF hands. CaM undergoes a
      conformational change upon binding to Ca(2+), which enables it to bind to
      specific proteins for specific responses. Here, we successfully photocontrolled
      CaM binding to its target peptide using the photochromic compound N-(4
      phenylazophenyl) maleimide (PAM), which reversibly undergoes cis-trans
      isomerization upon ultraviolet (UV) and visible (VIS) light irradiation. In order
      to specifically incorporate PAM, CaM mutants having reactive cysteine residues in
      the functional region were prepared; PAM was stoichiometrically incorporated into
      the cysteine residues in these mutants. Further, we prepared the target peptide,
      M13, fused with yellow fluorescent protein (YFP) to monitor the CaM-M13 peptide
      interaction. The binding of the PAM-CaM mutants, N60C, D64C and M124C, to M13-YFP
      was reversibly photocontrolled upon UV-VIS light irradiation at appropriate
      Ca(2+) concentrations.

PMID- 19605461
TI  - Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces
      hydrogen sulfide.
AB  - Hydrogen sulfide (H(2)S) has been recognized as a smooth muscle relaxant.
      Cystathionine gamma-lyase, which is localized to smooth muscle, is thought to be
      the major H(2)S-producing enzyme in the thoracic aorta. Here we show that 3
      mercaptopyruvate sulfurtransferase (3MST) and cysteine aminotransferase (CAT) are
      localized to vascular endothelium in the thoracic aorta and produce H(2)S. Both
      3MST and CAT were localized to endothelium. Lysates of vascular endothelial cells
      produced H(2)S from cysteine and alpha-ketoglutarate. The present study provides
      a new insight into the production and release of H(2)S as a smooth muscle
      relaxant from vascular endothelium.

PMID- 19605462
TI  - NMR solution structure of HP0827 (O25501_HELPY) from Helicobacter pylori: model
      of the possible RNA-binding site.
AB  - The HP0827 protein is an 82-residue protein identified as a putative ss-DNA
      binding protein 12RNP2 Precursor from Helicobacter pylori. Here, we have
      determined 3D structure of HP0827 using Nuclear Magnetic Resonance. It has a
      ferredoxin-like fold, beta1-alpha1-beta2-beta3-alpha2-beta4 (alpha; alpha-helix
      and beta; beta-sheet) and ribonucleoprotein (RNP) motifs which are thought to be
      important in RNA binding. By using structural homologues search and analyzing
      electrostatic potential of surface, we could compared HP0827 with other RNA
      binding proteins (sex-lethal, T-cell restricted intracellular antigen-1, U1A) to
      predict RNA-binding sites of HP0827. We could predict that beta sheets of HP0827,
      especially beta1 and beta3, are primary region for RNA binding. Consequently,
      similar to other RNA-binding proteins, RNP motifs (Y5, F45, F47), positively
      charged and hydrophobic regions (K32, R37, K40, K41, K43, R70, R73) are proposed
      as a putative RNA-binding sites. In addition, differences in amino acids
      composition of RNP motifs, N, C-terminal residues, loop-region fold and the
      orientation of alpha1-helix with other RNA recognition motif proteins could give
      specific biological functions to HP0827. Finally, the study on natural RNA target
      is also important to completely understand the biological function of HP0827.

PMID- 19605463
TI  - Mutational analysis of the GTP-binding motif of FlhF which regulates the number
      and placement of the polar flagellum in Vibrio alginolyticus.
AB  - Precise regulation of the number and placement of flagella is critical for the
      mono-flagellated bacterium Vibrio alginolyticus to swim efficiently. We
      previously proposed a model in which the putative GTPase FlhF determines the
      polar location and generation of the flagellum, the putative ATPase FlhG
      interacts with FlhF to prevent FlhF from localizing to the pole, and thus FlhG
      negatively regulates the flagellar number in V. alginolyticus cells. To
      investigate the role of the GTP-binding motif of FlhF, we generated a series of
      alanine-replacement mutations at the positions that are highly conserved among
      homologous proteins. The results indicate that there is a correlation between the
      polar localization and the ability to produce flagella in the mutants. We
      investigated whether the mutations in the GTP-binding motif affected the ability
      to interact with FlhG. In contrast to our prediction, no significant difference
      was detected in the interaction with FlhG between the wild-type and mutant FlhFs.
      We showed that the GTP-binding motif of FlhF is important for polar localization
      of the flagellum but not for the interaction with FlhG.

PMID- 19605465
TI  - Importance of the hydrogen bonding network including Asp52 for catalysis, as
      revealed by Asn59 mutant hen egg-white lysozymes.
AB  - In the catalysis of sugar hydrolysis by hen egg-white lysozyme, Asp52 is thought
      to stabilize the reaction intermediate. This residue is involved in the well
      ordered hydrogen bonding network including Asn46, Asp48, Ser50 and Asn59 on the
      anti-parallel beta-sheet, designated as a 'platform', on which the substrate
      sugar sits. To reveal the role of this hydrogen bonding network in the
      hydrolysis, we characterized Asn59 mutants by biochemical and crystallographic
      studies. Surprisingly, the introduction of only a methylene group by the Asn59Gln
      mutation markedly reduced the bacteriolytic activity and abolished the hydrolytic
      activity towards the synthetic substrate, PNP-(GlcNAc)(5). A similar result was
      also obtained with the Asn59Asp mutant. The crystal structure of the Asn59Asp
      mutant in complex with the substrate analogue revealed that, as in the wild-type,
      the (GlcNAc)(3) was bound in the A-B-C subsites. The reduced activity would be
      caused by subtle changes in the side-chain orientations as well as the
      electrostatic characteristics of Asp59, resulting in the rearrangement of the
      hydrogen bonding network of the platform. These results suggest that the precise
      locations of these 'platform' residues, maintained by the well-ordered hydrogen
      bonding network, are crucial for efficient hydrolysis.

PMID- 19605464
TI  - Membrane localization of protein-tyrosine phosphatase 1B is essential for its
      activation of sterol regulatory element-binding protein-1 gene expression and
      consequent hypertriglyceridaemia.
AB  - Protein-tyrosine phosphatase 1B (PTP1B) is a major regulator of insulin
      sensitivity. We have described a novel action of PTP1B in the induction of sterol
      regulatory element-binding protein-1 (SREBP-1) gene expression through activation
      of protein phosphatase 2A (PP2A). PTP1B is anchored to the endoplasmic reticulum
      membrane via its C-terminal tail. We have previously reported that membrane
      localization of PTP1B is essential for PP2A activation, which is crucial for
      enhancing SREBP-1 gene expression in in vitro experiments. In this study, we
      further investigated the physiological importance of membrane localization of
      PTP1B in vivo. We found that transient liver-specific overexpression of wild-type
      PTP1B (PTP1B-WT) using adenovirus-mediated gene transfer was associated with
      hypertriglyceridaemia and enhanced hepatic SREBP-1 gene expression in mice.
      However, overexpression of the C-terminal truncated PTP1B (PTP1BDeltaCT) failed
      to increase hepatic SREBP-1 expression or serum triglyceride levels, despite
      causing insulin resistance. Our results indicate that activation of PTP1B in the
      liver could induce hypertriglyceridaemia and that anchoring of PTP1B to the
      membrane is crucial for its action.

PMID- 19605466
TI  - Glutamate64 to glycine substitution in G1 beta-bulge of ubiquitin impairs
      function and stabilizes structure of the protein.
AB  - Ubiquitin is a globular protein with a highly conserved sequence. Sequence
      conservation and compact structure make it an ideal protein for structure
      function studies. One of the atypical secondary structural features found in
      ubiquitin is a parallel G1 beta-bulge. Glutamate at 64 is the first residue of
      this beta-bulge and the third residue in a type II turn. However, glycine is seen
      in these positions in several proteins. To understand the effects of substitution
      of glutamate64 by glycine on the structure, stability and function of ubiquitin,
      mutant UbE64G has been constructed and characterized in Saccharomyces cerevisiae.
      The secondary and tertiary structures of UbE64G mutant protein are only
      marginally different from wild-type protein (UbWt) and fluorescent form of
      ubiquitin (UbF45W). The earlier studies have shown that the structure and
      stability of UbWt and UbF45W were similar. However, UbE64G has less surface
      hydrophobicity than UbWt. UbE64G is found to be more stable compared with UbF45W
      towards guanidinium chloride induced denaturation. In vivo, complementation shows
      substrate proteins with Pro as the N-terminal residue, which undergo
      ubiquitination, have extended half-lives with UbE64G. This altered preference for
      Pro as opposed to Met might be related to natural preference of glutamate at 64th
      position in ubiquitin.

PMID- 19605467
TI  - Genetic mapping of Cgdef gene controlling accumulation of 7S globulin (beta
      conglycinin) subunits in soybean seeds.
AB  - Soy protein consists of mainly 7S globulin (beta-conglycinin) and 11S globulin
      (glycinin). The 7S globulin exerts favorable and unfavorable effects on human
      nutrition, food processing, and human health. Therefore, it is important for the
      improvement of the soy protein to control the content of 7S globulin. A mutant
      line lacking the 7S globulin was induced by gamma-ray irradiation, and the
      deficiency is controlled by a single recessive gene, cgdef. The Cgdef gene,
      despite its potential for improvement of the soy protein, has not been assigned
      to a linkage group of a soybean genetic map. We crossed "Mo-shi-dou Gong 503"
      with plants homozygous or heterozygous for the Cgdef allele and screened an F2
      mapping population that segregated with the cgdef allele to locate the Cgdef gene
      on a soybean genetic map. By linkage analysis, we assigned the Cgdef gene to
      chromosome 19 at the position between the Satt523 and Sat_388 simple sequence
      repeat (SSR) markers. Six SSR markers (Sat_134, Sat_405, Satt143, Satt398,
      Sat_195, and Satt694) and 2 amplified fragment length polymorphism markers
      identified previously were mapped at the same position of the Cgdef gene. These
      markers should enable to conduct map-based cloning of the Cgdef gene.

PMID- 19605468
TI  - Right atrium traumatic rupture presenting as chronic tamponade.
AB  - Non-penetrating cardiac traumatisms can cause cardiac rupture, myocardial
      contusion or, rarely, commotio cordis. In cases of rupture of a cardiac cavity,
      acute and severe cardiac tamponade almost invariably occurs. This paper presents
      an exceptionally unusual case of non-penetrating cardiac trauma resulting in
      right atrium rupture contained by the pericardial cavity. A situation of
      exceptional hemodynamic balance was established with subacute, progressive
      cardiac tamponade that evolved during three months, presenting gradual right
      heart failure instead of the expected acute and severe cardiac tamponade. The
      rupture of the atrium was successfully repaired.

PMID- 19605469
TI  - Cutting precision in a novel aortic valve resection tool. Research in progress.
AB  - BACKGROUND: We recently demonstrated the first in-vitro cutting results of a
      minimal-invasive aortic valve resection tool. The current study was designed to
      assess the cutting accuracy of this new device improved by the implementation of
      a linear motor-based propulsion unit. METHODS: Native aortic valves of isolated
      swine hearts (valve diameter 17.8+/-0.9 mm, mean+/-S.D.) were artificially
      stenosed and calcified (n=7). Subsequently, valves were resected by the use of a
      new aortic valve resection tool. The cutting process was performed by fitting the
      instrument with foldable Nitinol cutting blades (diameter 15 mm) and two software
      operated linear motors combined with separated manual rotation. Aortic valve area
      was measured pre- and postprocedure by software-guided binary area calculation.
      Aortic valve residue has been determined and the grade of accuracy has been
      assessed via calculating the average midpoint of the neoannulus. Furthermore,
      radial deviation of concentricity was calculated and cutting time was measured.
      RESULTS: Aortic valve resection was successful in all cases and nearly all
      leaflets (2.5+/-0.4) with a weight of 0.22+/-0.12 g were cut. Aortic valve area
      increased significantly (0.3+/-0.1 cm(2) vs. 1.1+/-0.2 cm(2), P<0.001) with a
      mean cutting time of 49.7+/-15.0 s. Mean lateral leaflet rim within the annulus
      was 3.2+/-3.2 mm. Cutting precision revealed a median deviation of the cutting
      ring from the desired position of 1.3+/-0.6 mm (y-axis) and 1.4+/-0.5 mm (x
      axis). Median center deviation of the cutting ring was 2.6+/-0.8 mm. CONCLUSIONS:
      The present study clearly confirmed ability of an accelerated cutting of stenotic
      aortic valve by the aortic valve resection tool. Nearly all leaflets were cut and
      a small rim was left within the annulus, hence providing an ideal 'landing zone'
      for the new prosthesis. Nevertheless, the aortic valve resection tool should be
      enhanced by adding a centering mechanism, thus achieving a more precise cutting
      process in order to avoid secondary damage.

PMID- 19605470
TI  - Selective expression of human immunodeficiency virus Nef in specific immune cell
      populations of transgenic mice is associated with distinct AIDS-like phenotypes.
AB  - We previously reported that CD4C/human immunodeficiency virus (HIV)(Nef)
      transgenic (Tg) mice, expressing Nef in CD4(+) T cells and cells of the
      macrophage/dendritic cell (DC) lineage, develop a severe AIDS-like disease,
      characterized by depletion of CD4(+) T cells, as well as lung, heart, and kidney
      diseases. In order to determine the contribution of distinct populations of
      hematopoietic cells to the development of this AIDS-like disease, five additional
      Tg strains expressing Nef through restricted cell-specific regulatory elements
      were generated. These Tg strains express Nef in CD4(+) T cells, DCs, and
      macrophages (CD4E/HIV(Nef)); in CD4(+) T cells and DCs (mCD4/HIV(Nef) and
      CD4F/HIV(Nef)); in macrophages and DCs (CD68/HIV(Nef)); or mainly in DCs
      (CD11c/HIV(Nef)). None of these Tg strains developed significant lung and kidney
      diseases, suggesting the existence of as-yet-unidentified Nef-expressing cell
      subset(s) that are responsible for inducing organ disease in CD4C/HIV(Nef) Tg
      mice. Mice from all five strains developed persistent oral carriage of Candida
      albicans, suggesting an impaired immune function. Only strains expressing Nef in
      CD4(+) T cells showed CD4(+) T-cell depletion, activation, and apoptosis. These
      results demonstrate that expression of Nef in CD4(+) T cells is the primary
      determinant of their depletion. Therefore, the pattern of Nef expression in
      specific cell population(s) largely determines the nature of the resulting
      pathological changes.

PMID- 19605471
TI  - Class III phosphatidylinositol 4-kinase alpha and beta are novel host factor
      regulators of hepatitis C virus replication.
AB  - Host factor pathways are known to be essential for hepatitis C virus (HCV)
      infection and replication in human liver cells. To search for novel host factor
      proteins required for HCV replication, we screened a subgenomic genotype 1b
      replicon cell line (Luc-1b) with a kinome and druggable collection of 20,779
      siRNAs. We identified and validated several enzymes required for HCV replication,
      including class III phosphatidylinositol 4-kinases (PI4KA and PI4KB), carbamoyl
      phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), and
      mevalonate (diphospho) decarboxylase. Knockdown of PI4KA could inhibit the
      replication and/or HCV RNA levels of the two subgenomic genotype 1b clones (SG-1b
      and Luc-1b), two subgenomic genotype 1a clones (SG-1a and Luc-1a), JFH-1 genotype
      2a infectious virus (JFH1-2a), and the genomic genotype 1a (FL-1a) replicon. In
      contrast, PI4KB knockdown inhibited replication and/or HCV RNA levels of Luc-1b,
      SG-1b, and Luc-1a replicons. The small molecule inhibitor, PIK93, was found to
      block subgenomic genotype 1b (Luc-1b), subgenomic genotype 1a (Luc-1a), and
      genomic genotype 2a (JFH1-2a) infectious virus replication in the nanomolar
      range. PIK93 was characterized by using quantitative chemical proteomics and in
      vitro biochemical assays to demonstrate PIK93 is a bone fide PI4KA and PI4KB
      inhibitor. Our data demonstrate that genetic or pharmacological modulation of
      PI4KA and PI4KB inhibits multiple genotypes of HCV and represents a novel
      druggable class of therapeutic targets for HCV infection.

PMID- 19605472
TI  - Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's
      sarcoma-associated herpesvirus.
AB  - K3/MIR1 and K5/MIR2 of Kaposi's sarcoma-associated herpesvirus (KSHV) are viral
      members of the membrane-associated RING-CH (MARCH) ubiquitin ligase family and
      contribute to viral immune evasion by directing the conjugation of ubiquitin to
      immunostimulatory transmembrane proteins. In a quantitative proteomic screen for
      novel host cell proteins downregulated by viral immunomodulators, we previously
      observed that K5, as well as the human immunodeficiency virus type 1 (HIV-1)
      immunomodulator VPU, reduced steady-state levels of bone marrow stromal cell
      antigen 2 (BST2; also called CD317 or tetherin), suggesting that BST2 might be a
      novel substrate of K5 and VPU. Recent work revealed that in the absence of VPU,
      HIV-1 virions are tethered to the plasma membrane in BST2-expressing HeLa cells.
      By targeting BST2, K5 might thus similarly overcome an innate antiviral host
      defense mechanism. Here we establish that despite its type II transmembrane
      topology and carboxy-terminal glycosylphosphatidylinositol (GPI) anchor, BST2
      represents a bona fide target of K5 that is downregulated during primary
      infection by and reactivation of KSHV. Upon exit of the protein from the
      endoplasmic reticulum, lysines in the short amino-terminal domain of BST2 are
      ubiquitinated by K5, resulting in rapid degradation of BST2. Ubiquitination of
      BST2 is required for degradation, since BST2 lacking cytosolic lysines was K5
      resistant and ubiquitin depletion by proteasome inhibitors restored BST2 surface
      expression. Thus, BST2 represents the first type II transmembrane protein
      targeted by K5 and the first example of a protein that is both ubiquitinated and
      GPI linked. We further demonstrate that KSHV release is decreased in the absence
      of K5 in a BST2-dependent manner, suggesting that K5 contributes to the evasion
      of intracellular antiviral defense programs.

PMID- 19605473
TI  - Ganglioside GT1b is a putative host cell receptor for the Merkel cell
      polyomavirus.
AB  - The Merkel cell polyomavirus (MCPyV) was identified recently in human Merkel cell
      carcinomas, an aggressive neuroendocrine skin cancer. Here, we identify a
      putative host cell receptor for MCPyV. We found that recombinant MCPyV VP1
      pentameric capsomeres both hemagglutinated sheep red blood cells and interacted
      with ganglioside GT1b in a sucrose gradient flotation assay. Structural
      differences between the analyzed gangliosides suggest that MCPyV VP1 likely
      interacts with sialic acids on both branches of the GT1b carbohydrate chain.
      Identification of a potential host cell receptor for MCPyV will aid in the
      elucidation of its entry mechanism and pathophysiology.

PMID- 19605474
TI  - ADAR1 interacts with PKR during human immunodeficiency virus infection of
      lymphocytes and contributes to viral replication.
AB  - The interferon-induced protein kinase RNA activated (PKR) is activated after
      virus infection. This activation is transient during the human immunodeficiency
      virus type 1 (HIV-1) infection of lymphocytes, and the protein is not activated
      at the peak of infection. We observed that interferon-induced adenosine deaminase
      acting on RNA 1-p150 (ADAR1-p150) and ADAR1-p110 expression increases while the
      virus replicates actively. Furthermore, both forms of ADAR1 show enhanced
      interactions with PKR at the peak of HIV infection, suggesting a role for this
      protein in the regulation of PKR activation. We observed that ADAR1-p150, as
      previously shown for the TAR RNA binding protein (TRBP), reverses the PKR
      inhibition of HIV expression and production in HEK 293T cells. This activity
      requires the Z-DNA binding motif and the three double-stranded RNA binding
      domains but not the catalytic domain. In astrocytic cells, ADAR1-p150 increased
      HIV expression and production to an extent similar to that of TRBP. Small
      interfering RNAs against ADAR1-p150 moderately decreased HIV production. These
      results indicate that two interferon-induced proteins, ADAR1 and PKR, have
      antagonistic functions on HIV production. They suggest that ADAR1 and TRBP belong
      to a multiprotein complex that inhibits PKR during the HIV infection of
      lymphocytes.

PMID- 19605475
TI  - Impact of HLA in mother and child on disease progression of pediatric human
      immunodeficiency virus type 1 infection.
AB  - A broad Gag-specific CD8(+) T-cell response is associated with effective control
      of adult human immunodeficiency virus (HIV) infection. The association of certain
      HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune
      control is linked to mutations within Gag epitopes presented by these alleles
      that allow HIV to evade the immune response but that also reduce viral
      replicative capacity. Transmission of such viruses containing mutations within
      Gag epitopes results in lower viral loads in adult recipients. In this study of
      pediatric infection, we tested the hypothesis that children may tend to progress
      relatively slowly if either they themselves possess one of the protective HLA-B
      alleles or the mother possesses one of these alleles, thereby transmitting a low
      fitness virus to the child. We analyzed HLA type, CD8(+) T-cell responses, and
      viral sequence changes for 61 mother-child pairs from Durban, South Africa, who
      were monitored from birth. Slow progression was significantly associated with the
      mother or child possessing one of the protective HLA-B alleles, and more
      significantly so when the protective allele was not shared by mother and child (P
      = 0.007). Slow progressors tended to make CD8(+) T-cell responses to Gag epitopes
      presented by the protective HLA-B alleles, in contrast to progressors expressing
      the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the
      protective alleles were significantly more likely to transmit escape variants
      within the Gag epitopes presented by those alleles than mothers not expressing
      those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape
      mutations was observed in all slow-progressing children whose mothers possessed
      protective HLA-B alleles. These data show that HLA class I alleles influence
      disease progression in pediatric as well as adult infection, both as a result of
      the CD8(+) T-cell responses generated in the child and through the transmission
      of low-fitness viruses by the mother.

PMID- 19605476
TI  - Genetic inactivation of poliovirus infectivity by increasing the frequencies of
      CpG and UpA dinucleotides within and across synonymous capsid region codons.
AB  - Replicative fitness of poliovirus can be modulated systematically by replacement
      of preferred capsid region codons with synonymous unpreferred codons. To
      determine the key genetic contributors to fitness reduction, we introduced
      different sets of synonymous codons into the capsid coding region of an
      infectious clone derived from the type 2 prototype strain MEF-1. Replicative
      fitness in HeLa cells, measured by plaque areas and virus yields in single-step
      growth experiments, decreased sharply with increased frequencies of the
      dinucleotides CpG (suppressed in higher eukaryotes and most RNA viruses) and UpA
      (suppressed nearly universally). Replacement of MEF-1 capsid codons with the
      corresponding codons from another type 2 prototype strain (Lansing), a
      randomization of MEF-1 synonymous codons, increased the %G+C without increasing
      CpG, and reductions in the effective number of codons used had much smaller
      individual effects on fitness. Poliovirus fitness was reduced to the threshold of
      viability when CpG and UpA dinucleotides were saturated within and across
      synonymous codons of a capsid region interval representing only approximately 9%
      of the total genome. Codon replacements were associated with moderate decreases
      in total virion production but large decreases in the specific infectivities of
      intact poliovirions and viral RNAs. Replication of codon replacement viruses, but
      not MEF-1, was temperature sensitive at 39.5 degrees C. Synthesis and processing
      of viral intracellular proteins were largely unaltered in most codon replacement
      constructs. Replacement of natural codons with synonymous codons with increased
      frequencies of CpG and UpA dinucleotides may offer a general approach to the
      development of attenuated vaccines with well-defined antigenicities and very high
      genetic stabilities.

PMID- 19605477
TI  - The hepatitis C virus core protein contains a BH3 domain that regulates apoptosis
      through specific interaction with human Mcl-1.
AB  - The hepatitis C virus (HCV) core protein is known to modulate apoptosis and
      contribute to viral replication and pathogenesis. In this study, we have
      identified a Bcl-2 homology 3 (BH3) domain in the core protein that is essential
      for its proapoptotic property. Coimmunoprecipitation experiments showed that the
      core protein interacts specifically with the human myeloid cell factor 1 (Mcl-1),
      a prosurvival member of the Bcl-2 family, but not with other prosurvival members
      (Bcl-X(L) and Bcl-w). Moreover, the overexpression of Mcl-1 protects against core
      induced apoptosis. By using peptide mimetics, core was found to release
      cytochrome c from isolated mitochondria when complemented with Bad. Thus, core is
      a bona fide BH3-only protein having properties similar to those of Noxa, a BH3
      only member of the Bcl-2 family that binds preferentially to Mcl-1. There are
      three critical hydrophobic residues in the BH3 domain of the core protein, and
      they are essential for the proapoptotic property of the core protein.
      Furthermore, the genotype 1b core protein is more effective than the genotype 2a
      core protein in inducing apoptosis due to a single-amino-acid difference at one
      of these hydrophobic residues (residue 119). Replacing this residue in the J6/JFH
      1 infectious clone (genotype 2a) with the corresponding amino acid in the
      genotype 1b core protein produced a mutant virus, J6/JFH-1(V119L), which induced
      significantly higher levels of apoptosis in the infected cells than the parental
      J6/JFH-1 virus. Furthermore, the core protein of J6/JFH-1(V119L), but not that of
      J6/JFH-1, interacted with Mcl-1 in virus-infected cells. Taken together, the core
      protein is a novel BH3-only viral homologue that contributes to the induction of
      apoptosis during HCV infection.

PMID- 19605478
TI  - Characterization of hepatitis C virus core protein multimerization and membrane
      envelopment: revelation of a cascade of core-membrane interactions.
AB  - The molecular basis underlying hepatitis C virus (HCV) core protein maturation
      and morphogenesis remains elusive. We characterized the concerted events
      associated with core protein multimerization and interaction with membranes.
      Analyses of core proteins expressed from a subgenomic system showed that the
      signal sequence located between the core and envelope glycoprotein E1 is critical
      for core association with endoplasmic reticula (ER)/late endosomes and the core's
      envelopment by membranes, which was judged by the core's acquisition of
      resistance to proteinase K digestion. Despite exerting an inhibitory effect on
      the core's association with membranes, (Z-LL)(2)-ketone, a specific inhibitor of
      signal peptide peptidase (SPP), did not affect core multimeric complex formation,
      suggesting that oligomeric core complex formation proceeds prior to or upon core
      attachment to membranes. Protease-resistant core complexes that contained both
      innate and processed proteins were detected in the presence of (Z-LL)(2)-ketone,
      implying that core envelopment occurs after intramembrane cleavage. Mutations of
      the core that prevent signal peptide cleavage or coexpression with an SPP loss-of
      function D219A mutant decreased the core's envelopment, demonstrating that SPP
      mediated cleavage is required for core envelopment. Analyses of core mutants with
      a deletion in domain I revealed that this domain contains sequences crucial for
      core envelopment. The core proteins expressed by infectious JFH1 and Jc1 RNAs in
      Huh7 cells also assembled into a multimeric complex, associated with ER/late
      endosomal membranes, and were enveloped by membranes. Treatment with (Z-LL)(2)
      ketone or coexpression with D219A mutant SPP interfered with both core
      envelopment and infectious HCV production, indicating a critical role of core
      envelopment in HCV morphogenesis. The results provide mechanistic insights into
      the sequential and coordinated processes during the association of the HCV core
      protein with membranes in the early phase of virus maturation and morphogenesis.

PMID- 19605480
TI  - Novel translation products from simian immunodeficiency virus SIVmac239 Env
      encoding mRNA contain both Rev and cryptic T-cell epitopes.
AB  - Understanding the correlates of immune protection against human immunodeficiency
      virus and simian immunodeficiency virus (SIV) will require defining the entire
      cellular immune response against the viruses. Here, we define two novel
      translation products from the SIV env mRNA that are targeted by the T-cell
      response in SIV-infected rhesus macaques. The shorter product is a subset of the
      larger product, which contains both the first exon of the Rev protein and a
      translated portion of the rev intron. Our data suggest that the translation of
      viral alternate reading frames may be an important source of T-cell epitopes,
      including epitopes normally derived from functional proteins.

PMID- 19605479
TI  - Interactions between viral and prokaryotic pathogens in a mixed infection with
      cardiovirus and mycoplasma.
AB  - In the natural environment, animal and plant viruses often share ecological
      niches with microorganisms, but the interactions between these pathogens,
      although potentially having important implications, are poorly investigated. The
      present report demonstrates, in a model system, profound mutual effects of
      mycoplasma and cardioviruses in animal cell cultures. In contrast to mycoplasma
      free cells, cultures contaminated with Mycoplasma hyorhinis responded to
      infection with encephalomyocarditis virus (EMCV), a picornavirus, but not with
      poliovirus (also a picornavirus), with a strong activation of a DNase(s), as
      evidenced by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin
      nick end labeling) immunofluorescence assay and electrophoretic analysis of host
      DNA. This degradation was reminiscent of that observed upon apoptosis but was
      caspase independent, judging by the failure of the specific pan-caspase inhibitor
      Q-VD-OPh to prevent it. The electrophoretic mobility of the enzyme responsible
      for DNA degradation and dependence of its activity on ionic conditions strongly
      suggested that it was represented by a DNase(s) of mycoplasma origin. In cells
      not infected with EMCV, the relevant DNase was dormant. The possibility is
      discussed that activation of the mycoplasma DNase might be linked to a relatively
      early increase in permeability of plasma membrane of the infected cells caused by
      EMCV. This type of unanticipated virus-mycoplasma "cooperation" may exemplify the
      complexity of pathogen-host interactions under conditions when viruses and
      microorganisms are infecting the same host. In the course of the present study,
      it was also demonstrated that pan-caspase inhibitor zVAD(OMe).fmk strongly
      suppressed cardiovirus polyprotein processing, illustrating an additional pitfall
      in investigations of viral effects on the apoptotic system of host cells.

PMID- 19605481
TI  - RNA-based regulation of transcription and translation of aureusvirus subgenomic
      mRNA1.
AB  - Cucumber leaf spot virus (CLSV) is an aureusvirus (family Tombusviridae) that has
      a positive-sense RNA genome encoding five proteins. During infections, CLSV
      transcribes two subgenomic (sg) mRNAs and the larger of the two, sg mRNA1,
      encodes coat protein. Here, the viral RNA sequences and structures that regulate
      transcription and translation of CLSV sg mRNA1 were investigated. A medium-range
      RNA-RNA interaction in the CLSV genome, spanning 148 nucleotides, was found to be
      required for the efficient transcription of sg mRNA1. Further analysis indicated
      that the structure formed by this interaction acted as an attenuation signal
      required for transcription of sg mRNA1 via a premature termination mechanism.
      Translation of coat protein from sg mRNA1 was determined to be facilitated by a
      5'-terminal stem-loop structure in the message that resembled a tRNA anticodon
      stem-loop. The results from mutational analysis indicated that the 5'-terminal
      stem-loop mediated efficient base pairing with a 3'-cap-independent translational
      enhancer at the 3' end of the message, leading to efficient translation of coat
      protein from sg mRNA1. Comparison of the regulatory RNA structures for sg mRNA1
      of CLSV to those used by the closely related tombusviruses and certain cellular
      RNAs revealed interesting differences and similarities that provide evolutionary
      and mechanistic insights into RNA-based regulatory strategies.

PMID- 19605482
TI  - The carboxy-terminal tail of human cytomegalovirus (HCMV) US28 regulates both
      chemokine-independent and chemokine-dependent signaling in HCMV-infected cells.
AB  - The human cytomegalovirus (HCMV)-encoded G-protein-coupled receptor (GPCR) US28
      is a potent activator of a number of signaling pathways in HCMV-infected cells.
      The intracellular carboxy-terminal domain of US28 contains residues critical for
      the regulation of US28 signaling in heterologous expression systems; however, the
      role that this domain plays during HCMV infection remains unknown. For this
      study, we constructed an HCMV recombinant virus encoding a carboxy-terminal
      domain truncation mutant of US28, FLAG-US28/1-314, to investigate the role that
      this domain plays in US28 signaling. We demonstrate that US28/1-314 exhibits a
      more potent phospholipase C-beta (PLC-beta) signal than does wild-type US28,
      indicating that the carboxy-terminal domain plays an important role in regulating
      agonist-independent signaling in infected cells. Moreover, HMCV-infected cells
      expressing the US28/1-314 mutant exhibit a prolonged calcium signal in response
      to CCL5, indicating that the US28 carboxy-terminal domain also regulates agonist
      dependent signaling. Finally, while the chemokine CX3CL1 behaves as an inverse
      agonist or inhibitor of constitutive US28 signaling to PLC-beta, we demonstrate
      that CX3CL1 functions as an agonist with regard to US28-stimulated calcium
      release. This study is the first to demonstrate that the carboxy terminus of US28
      controls US28 signaling in the context of HCMV infection and indicates that
      chemokines such as CX3CL1 can decrease constitutive US28 signals and yet
      simultaneously promote nonconstitutive US28 signals.

PMID- 19605484
TI  - Selective-advantage profile of human immunodeficiency virus type 1 integrase
      mutants explains in vivo evolution of raltegravir resistance genotypes.
AB  - The emergence of human immunodeficiency virus type 1 resistance to raltegravir,
      an integrase strand transfer inhibitor, follows distinct and independent genetic
      pathways, among which the N155H and Q148HKR pathways are the most frequently
      encountered in treated patients. After prolonged viral escape, mutants of the
      N155H pathway are replaced by mutants of the Q148HKR pathway. We have examined
      the mechanisms driving this evolutionary pattern using an approach that assesses
      the selective advantage of site-directed mutant viruses as a function of drug
      concentration. These selective-advantage curves revealed that among single
      mutants, N155H had the highest and the widest (1 to 500 nM) selective-advantage
      profile. Despite the higher 50% inhibitory concentration, Q148H displayed a lower
      and narrower (10 to 100 nM) selective-advantage profile. Among double mutants,
      the highest and widest selective-advantage profile was seen with G140S+Q148H.
      This finding likely explains why N155H can be selected early in the course of RAL
      resistance evolution in vivo but is later replaced by genotypes that include
      Q148HKR.

PMID- 19605483
TI  - The adenovirus E1B 55-kilodalton and E4 open reading frame 6 proteins limit
      phosphorylation of eIF2alpha during the late phase of infection.
AB  - During a productive infection, species C adenovirus reprograms the host cell to
      promote viral translation at the expense of cellular translation. The E1B 55
      kilodalton (E1B-55K) and E4 open reading frame 6 (E4orf6) proteins are important
      in this control of gene expression. As part of a ubiquitin-protein ligase, these
      viral proteins stimulate viral mRNA export, inhibit cellular mRNA export, promote
      viral gene expression, and direct the degradation of certain host proteins. We
      report here that the E1B-55K and E4orf6 proteins limited phosphorylation of
      eIF2alpha and the activation of the eIF2alpha kinase PKR. Phospho-eIF2alpha
      levels were observed to rise and fall at least twice during infection. The E1B
      55K and E4orf6 proteins prevented a third increase at late times of infection.
      PKR appeared to phosphorylate eIF2alpha only in the absence of E1B-55K/E4orf6
      function. PKR activation and eIF2alpha phosphorylation was unrelated to the
      cytoplasmic levels of the adenovirus inhibitor of PKR, VA-I RNA. Nonetheless,
      expression of a PKR inhibitor, the reovirus double-stranded RNA-binding protein
      sigma 3, prevented PKR activation and eIF2alpha phosphorylation. The sigma 3
      protein largely corrected the defect in viral late protein synthesis associated
      with the E1B-55K and E4orf6 mutant viruses without affecting cytoplasmic levels
      of the late viral mRNA. The ubiquitin-protein ligase activity associated with the
      E1B-55K/E4orf6 complex was necessary to prevent activation of PKR and
      phosphorylation of eIF2alpha. These findings reveal a new contribution of the E1B
      55K/E4orf6 complex to viral late protein synthesis and the existence of multiple
      layers of regulation imposed on eIF2alpha phosphorylation and PKR activation in
      adenovirus-infected cells.

PMID- 19605485
TI  - Single-reaction genomic amplification accelerates sequencing and vaccine
      production for classical and Swine origin human influenza a viruses.
AB  - Pandemic influenza A viruses that emerge from animal reservoirs are inevitable.
      Therefore, rapid genomic analysis and creation of vaccines are vital. We
      developed a multisegment reverse transcription-PCR (M-RTPCR) approach that
      simultaneously amplifies eight genomic RNA segments, irrespective of virus
      subtype. M-RTPCR amplicons can be used for high-throughput sequencing and/or
      cloned into modified reverse-genetics plasmids via regions of sequence identity.
      We used these procedures to rescue a contemporary H3N2 virus and a swine origin
      H1N1 virus directly from human swab specimens. Together, M-RTPCR and the modified
      reverse-genetics plasmids that we designed streamline the creation of vaccine
      seed stocks (9 to 12 days).

PMID- 19605486
TI  - Distribution of endogenous retroviruses in crocodilians.
AB  - Knowledge of endogenous retroviruses (ERVs) in crocodilians (Crocodylia) is
      limited, and their distribution among extant species is unclear. Here we analyzed
      the phylogenetic relationships of these retroelements in 20 species of
      crocodilians by studying the pro-pol gene. The results showed that crocodilian
      ERVs (CERVs) cluster into two major clades (CERV 1 and CERV 2). CERV 1 clustered
      as a sister group of the genus Gammaretrovirus, while CERV 2 clustered distantly
      with respect to all known ERVs. Interestingly, CERV 1 was found only in
      crocodiles (Crocodylidae). The data generated here could assist future studies
      aimed at identifying orthologous and paralogous ERVs among crocodilians.

PMID- 19605487
TI  - Hepatitis C virus core protein and cellular protein HAX-1 promote 5-fluorouracil
      mediated hepatocyte growth inhibition.
AB  - Hepatitis C virus (HCV) often causes chronic infection and may lead to
      hepatocellular carcinoma (HCC). We have shown previously that HCV core protein
      has pleiotropic functions, including transcriptional regulation of a number of
      cellular genes, although the mechanism for gene regulation remains unclear. In
      this study, a mammalian two-hybrid screen identified a novel binding partner, HS1
      associated protein X-1 (HAX-1), for HCV core protein from a human liver cDNA
      library. An association between HAX-1 and HCV core protein was further verified
      by confocal microscopy and coimmunoprecipitation in HepG2 cells expressing HCV
      core or full-length (FL) gene. Both HCV core protein and a chemotherapeutic agent
      for HCC, 5-flouorouracil (5-FU), are known to modulate p53. We examined here
      whether an association between core and HAX-1 has any functional relevance to p53
      modulation in 5-FU-treated cells. For this, the role of HAX-1 on 5-FU treatment
      was examined in HepG2 cells expressing HCV core or FL gene using cell
      proliferation, p53 expression, and caspase activation analysis. Cells expressing
      HCV-core or FL gene were more susceptible to 5-FU-induced growth inhibition than
      control cells, whereas cell survival was enhanced after suppression of HAX-1 by
      small interfering RNA. Further, 5-FU-mediated p53 expression was reduced with
      concurrent HAX-1 suppression in core- or polyprotein-expressing cells compared to
      control HepG2 cells, and caspase-2 and -7 activities were diminished. On the
      other hand, HCV core protein did not play a detectable role in 5-FU-mediated
      caspase-7 activation in the absence of functional p53 in Hep3B or Huh-7 cells.
      These observations underscore an association between HCV core and HAX-1, which
      promotes 5-FU mediated p53-dependent caspase-7 activation and hepatocyte growth
      inhibition.

PMID- 19605488
TI  - Artificial transmembrane oncoproteins smaller than the bovine papillomavirus E5
      protein redefine sequence requirements for activation of the platelet-derived
      growth factor beta receptor.
AB  - The bovine papillomavirus E5 protein (BPV E5) is a 44-amino-acid homodimeric
      transmembrane protein that binds directly to the transmembrane domain of the
      platelet-derived growth factor (PDGF) beta receptor and induces ligand
      independent receptor activation. Three specific features of BPV E5 are considered
      important for its ability to activate the PDGF beta receptor and transform mouse
      fibroblasts: a pair of C-terminal cysteines, a transmembrane glutamine, and a
      juxtamembrane aspartic acid. By using a new genetic technique to screen libraries
      expressing artificial transmembrane proteins for activators of the PDGF beta
      receptor, we isolated much smaller proteins, from 32 to 36 residues, that lack
      all three of these features yet still dimerize noncovalently, specifically
      activate the PDGF beta receptor via its transmembrane domain, and transform cells
      efficiently. The primary amino acid sequence of BPV E5 is virtually
      unrecognizable in some of these proteins, which share as few as seven consecutive
      amino acids with the viral protein. Thus, small artificial proteins that bear
      little resemblance to a viral oncoprotein can nevertheless productively interact
      with the same cellular target. We speculate that similar cellular proteins may
      exist but have been overlooked due to their small size and hydrophobicity.

PMID- 19605491
TI  - Immune evasion proteins enhance cytomegalovirus latency in the lungs.
AB  - CD8 T cells control cytomegalovirus (CMV) infection in bone marrow
      transplantation recipients and persist in latently infected lungs as effector
      memory cells for continuous sensing of reactivated viral gene expression. Here we
      have addressed the question of whether viral immunoevasins, glycoproteins that
      specifically interfere with antigen presentation to CD8 T cells, have an impact
      on viral latency in the murine model. The data show that deletion of immunoevasin
      genes in murine CMV accelerates the clearance of productive infection during
      hematopoietic reconstitution and leads to a reduced latent viral genome load,
      reduced latency-associated viral transcription, and a lower incidence of
      recurrence in lung explants.

PMID- 19605489
TI  - Derivation and characterization of a simian immunodeficiency virus SIVmac239
      variant with tropism for CXCR4.
AB  - Like human immunodeficiency virus type 1 (HIV-1), most simian immunodeficiency
      virus (SIV) strains use CCR5 to establish infection. However, while HIV-1 can
      acquire the ability to use CXCR4, SIVs that utilize CXCR4 have rarely been
      reported. To explore possible barriers against SIV coreceptor switching, we
      derived an R5X4 variant, termed 239-ST1, from the R5 clone SIVmac239 by serially
      passaging virus in CD4(+) CXCR4(+) CCR5(-) SupT1 cells. A 239-ST1 env clone,
      designated 239-ST1.2-32, used CXCR4 and CCR5 in cell-cell fusion and reporter
      virus infection assays and conferred the ability for rapid, cytopathic infection
      of SupT1 cells to SIVmac239. Viral replication was inhibitable by the CXCR4
      specific antagonist AMD3100, and replication was abrogated in a novel CXCR4(-)
      SupT1 line. Surprisingly, parental SIVmac239 exhibited low-level replication in
      SupT1 cells that was not observed in CXCR4(-) SupT1 cells. Only two mutations in
      the 239-ST1.2-32 Env, K47E in the C1 domain and L328W in the V3 loop, were
      required for CXCR4 use in cell-cell fusion assays, although two other V3 changes,
      N316K and I324M, improved CXCR4 use in infection assays. An Env cytoplasmic tail
      truncation, acquired during propagation of 239-ST1 in SupT1 cells, was not
      required. Compared with SIVmac239, 239-ST1.2-32 was more sensitive to
      neutralization by five of seven serum and plasma samples from SIVmac239-infected
      rhesus macaques and was approximately 50-fold more sensitive to soluble CD4.
      Thus, SIVmac239 can acquire the ability to use CXCR4 with high efficiency, but
      the changes required for this phenotype may be distinct from those for HIV-1
      CXCR4 use. This finding, along with the increased neutralization sensitivity of
      this CXCR4-using SIV, suggests a mechanism that could select strongly against
      this phenotype in vivo.

PMID- 19605490
TI  - Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication
      in residual viremia during recombinant HIV-1 poxvirus immunizations in patients
      with clinically undetectable viral loads on durable suppressive highly active
      antiretroviral therapy.
AB  - In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who
      achieve viral loads of <50 copies/ml during highly active antiretroviral therapy
      (HAART), low levels of plasma virus remain detectable for years by ultrasensitive
      methods. The relative contributions of ongoing virus replication and virus
      production from HIV-1 reservoirs to persistent low-level viremia during HAART
      remain controversial. HIV-1 vaccination of HAART-treated individuals provides a
      model for examining low-level viremia, as immunizations may facilitate virus
      replication and sequence evolution. In a phase 1 trial of modified vaccinia virus
      Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults
      receiving HAART, we assessed the prevalence of low-level viremia and sequence
      evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five
      copy sensitivity) assays. Viral evolution, consisting of new drug resistance
      mutations and novel amino acid changes within a relevant HLA-restricted allele
      (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205
      of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was
      significantly correlated with levels of viremia of between 6.5 and <50 copies/ml
      (P = 0.03) and was more likely to occur within epitopes presented by relevant HLA
      alleles (P < 0.001). These findings suggest that ongoing virus replication
      contributes to low-level viremia in patients on HAART and that this ongoing
      replication is subject to CD8(+) T-cell selective pressures.

PMID- 19605492
TI  - Upregulation of interleukin 7 receptor alpha and programmed death 1 marks an
      epitope-specific CD8+ T-cell response that disappears following primary Epstein
      Barr virus infection.
AB  - In immunocompetent individuals, the stability of the herpesvirus-host balance
      limits opportunities to study the disappearance of a virus-specific CD8(+) T-cell
      response. However, we noticed that in HLA-A 0201-positive infectious
      mononucleosis (IM) patients undergoing primary Epstein-Barr virus (EBV)
      infection, the initial CD8 response targets three EBV lytic antigen-derived
      epitopes, YVLDHLIVV (YVL), GLCTLVAML (GLC), and TLDYKPLSV (TLD), but only the YVL
      and GLC reactivities persist long-term; the TLD response disappears within 10 to
      27 months. While present, TLD-specific cells remained largely indistinguishable
      from YVL and GLC reactivities in many phenotypic and functional respects but
      showed unique temporal changes in two markers of T-cell fate, interleukin 7
      receptor alpha (IL-7Ralpha; CD127) and programmed death 1 (PD-1). Thus, following
      the antigen-driven downregulation of IL-7Ralpha seen on all populations in acute
      IM, in every case, the TLD-specific population recovered expression unusually
      quickly post-IM. As well, in four of six patients studied, TLD-specific cells
      showed very strong PD-1 upregulation in the last blood sample obtained before the
      cells' disappearance. Our data suggest that the disappearance of this individual
      epitope reactivity from an otherwise stable EBV-specific response (i) reflects a
      selective loss of cognate antigen restimulation (rather than of IL-7-dependent
      signals) and (ii) is immediately preceded, and perhaps mediated, by PD-1
      upregulation to unprecedented levels.

PMID- 19605493
TI  - Simian varicella virus induces apoptosis in monkey kidney cells by the intrinsic
      pathway and involves downregulation of bcl-2 expression.
AB  - Simian varicella virus (SVV) causes varicella in primates, becomes latent in
      ganglionic neurons, and reactivates to produce zoster. SVV produces a cytopathic
      effect in monkey kidney cells in tissue culture. To study the mechanism by which
      SVV-infected cells die, we examined markers of apoptosis 24 to 64 h postinfection
      (hpi). Western blot analysis of virus-infected cell lysates revealed a
      significant increase in the levels of the cleaved active form of caspase-3,
      accompanied by a parallel increase in caspase-3 activity at 40 to 64 hpi. Caspase
      9, a marker for the intrinsic pathway, was activated significantly in SVV
      infected cells at all time points, whereas trace levels of the active form of
      caspase-8, an extrinsic pathway marker, was detected only at 64 hpi. Bcl-2
      expression at the mRNA and protein levels was decreased by 50 to 70% throughout
      the course of virus infection. Release of cytochrome c, an activator of caspase
      9, from mitochondria into the cytoplasm was increased by 200% at 64 hpi. Analysis
      of Vero cells infected with SVV expressing green fluorescent protein (SVV-GFP) at
      64 hpi revealed colocalization of the active forms of caspase-3 and caspase-9 and
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling
      (TUNEL) staining with GFP. A significant decrease in the bcl-2 mRNA levels along
      with an abundance of mRNA specific for SVV genes 63, 40, and 21 was seen in the
      fraction of Vero cells that were infected with SVV-GFP. Together, these findings
      indicate that SVV induces apoptosis in cultured Vero cells through the intrinsic
      pathway in which Bcl-2 is downregulated.

PMID- 19605494
TI  - Sox2-positive dermal papilla cells specify hair follicle type in mammalian
      epidermis.
AB  - The dermal papilla comprises the specialised mesenchymal cells at the base of the
      hair follicle. Communication between dermal papilla cells and the overlying
      epithelium is essential for differentiation of the hair follicle lineages. We
      report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5
      onwards expression is confined to a subset of dermal papillae. In postnatal skin,
      Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles,
      whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal
      papillae. Using transgenic mice that express GFP under the control of the Sox2
      promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with
      Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal
      papilla gene signature, each subpopulation expressed distinct sets of genes.
      GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed
      neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and
      integrin pathways were prominent. In skin reconstitution assays, hair follicles
      failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-)
      CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed
      to form and only zigzag hairs were found. We have thus demonstrated a previously
      unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive
      cells specify particular hair follicle types.

PMID- 19605495
TI  - UNC-83 is a nuclear-specific cargo adaptor for kinesin-1-mediated nuclear
      migration.
AB  - Intracellular nuclear migration is essential for many cellular events including
      fertilization, establishment of polarity, division and differentiation. How
      nuclei migrate is not understood at the molecular level. The C. elegans KASH
      protein UNC-83 is required for nuclear migration and localizes to the outer
      nuclear membrane. UNC-83 interacts with the inner nuclear membrane SUN protein
      UNC-84 and is proposed to connect the cytoskeleton to the nuclear lamina. Here,
      we show that UNC-83 also interacts with the kinesin-1 light chain KLC-2, as
      identified in a yeast two-hybrid screen and confirmed by in vitro assays. UNC-83
      interacts with and recruits KLC-2 to the nuclear envelope in a heterologous
      tissue culture system. Additionally, analysis of mutant phenotypes demonstrated
      that both KLC-2 and the kinesin-1 heavy chain UNC-116 are required for nuclear
      migration. Finally, the requirement for UNC-83 in nuclear migration could be
      partially bypassed by expressing a synthetic outer nuclear membrane KLC-2::KASH
      fusion protein. Our data support a model in which UNC-83 plays a central role in
      nuclear migration by acting to bridge the nuclear envelope and as a kinesin-1
      cargo-specific adaptor so that motor-generated forces specifically move the
      nucleus as a single unit.

PMID- 19605497
TI  - The Tbx20 homologs midline and H15 specify ventral fate in the Drosophila
      melanogaster leg.
AB  - Regional fates in the developing limbs of Drosophila melanogaster are controlled
      by selector gene transcription factors. Ventral fate in the fly leg is specified
      by the expression of the ligand Wingless. We present evidence that midline and
      H15, members of the Tbx20 class of T-box transcription factors, are key mediators
      of the Wingless signal in the formation of the ventral region of the fly leg.
      midline and H15 are restricted to identical ventral domains of expression through
      activation by Wingless and repression by the dorsal signal Decapentaplegic.
      midline and H15 function redundantly and cell autonomously in the formation of
      ventral-specific structures. Conversely, midline is sufficient to induce ventral
      fate. Finally, the induction of ectopic ventral fate by mid is compromised when
      Wingless signaling is attenuated, suggesting that Wingless acts both upstream and
      in parallel with midline/H15 to specify ventral fate. Based on these results, we
      propose that midline and H15 may be considered as the selector genes for ventral
      leg fate.

PMID- 19605496
TI  - The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have
      overlapping function in C. elegans mesoderm development.
AB  - The C. elegans MS blastomere, born at the 7-cell stage of embryogenesis,
      generates primarily mesodermal cell types, including pharynx cells, body muscles
      and coelomocytes. A presumptive null mutation in the T-box factor gene tbx-35, a
      target of the MED-1 and MED-2 divergent GATA factors, was previously found to
      result in a profound decrease in the production of MS-derived tissues, although
      the tbx-35(-) embryonic arrest phenotype was variable. We report here that the NK
      2 class homeobox gene ceh-51 is a direct target of TBX-35 and at least one other
      factor, and that CEH-51 and TBX-35 share functions. Embryos homozygous for a ceh
      51 null mutation arrest as larvae with pharynx and muscle defects, although these
      tissues appear to be specified correctly. Loss of tbx-35 and ceh-51 together
      results in a synergistic phenotype resembling loss of med-1 and med-2.
      Overexpression of ceh-51 causes embryonic arrest and generation of ectopic body
      muscle and coelomocytes. Our data show that TBX-35 and CEH-51 have overlapping
      function in MS lineage development. As T-box regulators and NK-2 homeodomain
      factors are both important for heart development in Drosophila and vertebrates,
      our results suggest that these regulators function in a similar manner in C.
      elegans to specify a major precursor of mesoderm.

PMID- 19605498
TI  - Xenopus oocytes reactivate muscle gene transcription in transplanted somatic
      nuclei independently of myogenic factors.
AB  - Transplantation into eggs or oocytes is an effective means of achieving the
      reprogramming of somatic cell nuclei. We ask here whether the provision of gene
      specific transcription factors forms part of the mechanism by which a gene that
      is repressed in somatic cells is transcribed in oocytes. We find that M1 oocytes
      have an extremely strong transcription-inducing activity. They cause muscle genes
      of nuclei from non-muscle somatic cells, after injection into oocytes, to be
      transcribed to nearly the same extent as muscle genes in muscle cells. We show,
      surprisingly, that the myogenic factor MyoD and other known myogenic factors are
      not required to induce the transcription of muscle genes in a range of non-muscle
      somatic cell nuclei after transplantation to Xenopus oocytes. The overexpression
      of Id, a dominant-negative repressor of MyoD, prevents maternal MyoD from binding
      to its consensus sequences; nevertheless, muscle genes are activated in somatic
      nuclei to the same extent as without Id. We conclude that M1 oocytes can
      reprogram somatic nuclei in a different way to other experimental procedures:
      oocytes do not suppress the transcription of inappropriate genes and they
      activate a gene without the help of its known transcription factors. We suggest
      that these characteristics might be a special property of amphibian oocytes, and
      possibly of oocytes in general.

PMID- 19605499
TI  - Lats kinase is involved in the intestinal apical membrane integrity in the
      nematode Caenorhabditis elegans.
AB  - The roles of Lats kinases in the regulation of cell proliferation and apoptosis
      have been well established. Here we report new roles for Lats kinase in the
      integrity of the apical membrane structure. WTS-1, the C. elegans Lats homolog,
      localized primarily to the subapical region in the intestine. A loss-of-function
      mutation in wts-1 resulted in an early larval arrest and defects in the structure
      of the intestinal lumen. An electron microscopy study of terminally arrested wts
      1 mutant animals revealed numerous microvilli-containing lumen-like structures
      within the intestinal cells. The wts-1 phenotype was not caused by cell
      proliferation or apoptosis defects. Instead, we found that the wts-1 mutant
      animals exhibited gradual mislocalization of apical actin and apical junction
      proteins, suggesting that wts-1 normally suppresses the formation of extra apical
      membrane structures. Heat-shock-driven pulse-chase expression experiments showed
      that WTS-1 regulates the localization of newly synthesized apical actins. RNAi of
      the exocyst complex genes suppressed the mislocalization phenotype of wts-1
      mutation. Collectively, the data presented here suggest that Lats kinase plays
      important roles in the integrity of the apical membrane structure of intestinal
      cells.

PMID- 19605500
TI  - The Integrator subunits function in hematopoiesis by modulating Smad/BMP
      signaling.
AB  - Hematopoiesis, the dynamic process of blood cell development, is regulated by the
      activity of the bone morphogenetic protein (BMP) signaling pathway and by many
      transcription factors. However, the molecules and mechanisms that regulate
      BMP/Smad signaling in hematopoiesis are largely unknown. Here, we show that the
      Integrator complex, an evolutionarily conserved group of proteins, functions in
      zebrafish hematopoiesis by modulating Smad/BMP signaling. The Integrator complex
      proteins are known to directly interact with RNA polymerase II to mediate 3' end
      processing of U1 and U2 snRNAs. We have identified several subunits of the
      Integrator complex in zebrafish. Antisense morpholino-mediated knockdown of the
      Integrator subunit 5 (Ints5) in zebrafish embryos affects U1 and U2 snRNA
      processing, leading to aberrant splicing of smad1 and smad5 RNA, and reduced
      expression of the hematopoietic genes stem cell leukemia (scl, also known as
      tal1) and gata1. Blood smears from ints5 morphant embryos show arrested red blood
      cell differentiation, similar to scl-deficient embryos. Interestingly, targeting
      other Integrator subunits also leads to defects in smad5 RNA splicing and
      arrested hematopoiesis, suggesting that the Ints proteins function as a complex
      to regulate the BMP pathway during hematopoiesis. Our work establishes a link
      between the RNA processing machinery and the downstream effectors of BMP
      signaling, and reveals a new group of proteins that regulates the switch from
      primitive hematopoietic stem cell identity and blood cell differentiation by
      modulating Smad function.

PMID- 19605501
TI  - Rab5-mediated endocytosis of activin is not required for gene activation or long
      range signalling in Xenopus.
AB  - Morphogen gradients provide positional cues for cell fate specification and
      tissue patterning during embryonic development. One important aspect of morphogen
      function, the mechanism by which long-range signalling occurs, is still poorly
      understood. In Xenopus, members of the TGF-beta family such as the nodal-related
      proteins and activin act as morphogens to induce mesoderm and endoderm. In an
      effort to understand the mechanisms and dynamics of morphogen gradient formation,
      we have used fluorescently labelled activin to study ligand distribution and
      Smad2/Smad4 bimolecular fluorescence complementation (BiFC) to analyse, in a
      quantitative manner, the cellular response to induction. Our results indicate
      that labelled activin travels exclusively through the extracellular space and
      that its range is influenced by numbers of type II activin receptors on
      responding cells. Inhibition of endocytosis, by means of a dominant-negative form
      of Rab5, blocks internalisation of labelled activin, but does not affect the
      ability of cells to respond to activin and does not significantly influence
      signalling range. Together, our data indicate that long-range signalling in the
      early Xenopus embryo, in contrast to some other developmental systems, occurs
      through extracellular movement of ligand. Signalling range is not regulated by
      endocytosis, but is influenced by numbers of cognate receptors on the surfaces of
      responding cells.

PMID- 19605503
TI  - Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with
      S-1 for advanced gastric cancer with peritoneal metastasis.
AB  - BACKGROUND: A phase II study to evaluate the efficacy and tolerability of weekly
      i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric
      cancer patients with peritoneal metastasis. PATIENTS AND METHODS: Gastric cancer
      patients with peritoneal dissemination and/or cancer cells on peritoneal cytology
      were enrolled. PTX was administered i.v. at 50 mg/m(2) and i.p. at 20 mg/m(2) on
      days 1 and 8. S-1 was administered at 80 mg/m(2)/day for 14 consecutive days,
      followed by 7 days rest. The primary end point was the 1-year overall survival
      (OS) rate. Secondary end points were the response rate, efficacy against
      malignant ascites and safety. RESULTS: Forty patients were enrolled, including 21
      with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence
      and six with positive peritoneal cytology only. The median number of courses was
      7 (range 1-23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%).
      The overall response rate was 56% in 18 patients with target lesions. Malignant
      ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade
      3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%).
      CONCLUSION: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well
      tolerated and active in gastric cancer patients with peritoneal metastasis.

PMID- 19605504
TI  - A randomized multicenter phase II study comparing capecitabine with irinotecan or
      cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric
      junction.
AB  - BACKGROUND: The combination of irinotecan with 5-fluorouracil demonstrates
      efficacy with tolerable safety in the first-line treatment of metastatic
      gastroesophageal cancer (mGC). This randomized phase II trial compared for the
      first time capecitabine with irinotecan or cisplatin in this setting. PATIENTS
      AND METHODS: Patients were randomly assigned to receive 3-week cycles of
      capecitabine 1000 mg/m(2), twice daily for 14 days, with on day 1 either
      irinotecan 250 mg/m(2) (XI) or cisplatin 80 mg/m(2) (XP). The primary end point
      was overall response rate (ORR) and secondary end points included progression
      free survival (PFS), overall survival (OS) and safety. RESULTS: Of 118 patients
      recruited, 112 were eligible for safety analysis and 103 for efficacy analysis.
      In the XI and XP treatment arms, there were no marked differences in ORR, 37.7%
      versus 42.0%, and median PFS, 4.2 versus 4.8 months, although median OS was
      longer, 10.2 versus 7.9 months, respectively. Grade 3/4 toxicity was higher in
      the XP regimen for thrombocytes (18.2% versus 1.8%), nausea (23.6% versus12.3%)
      and vomiting (16.4% versus 1.8%) and in the XI arm for diarrhea (22.8% versus
      7.3%). CONCLUSION: The comparable activity and safety of the XI and XP regimens
      establish XI as a relevant platinum-free first-line treatment choice for patients
      with mGC.

PMID- 19605502
TI  - Regulation of bone formation and remodeling by G-protein-coupled receptor 48.
AB  - G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of
      the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of
      unknown function. Using a knockout mouse model, we have characterized the
      essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in
      mice results in a dramatic delay in osteoblast differentiation and
      mineralization, but not in chondrocyte proliferation and maturation, during
      embryonic bone formation. Postnatal bone remodeling is also significantly
      affected in Gpr48(-/-) mice, including the kinetic indices of bone formation
      rate, bone mineral density and osteoid formation, whereas the activity and number
      of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase
      staining. Examination of the molecular mechanism of Gpr48 action in bone
      formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to
      regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that
      Gpr48 significantly downregulates the expression levels of Atf4 target
      genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp)
      and collagen. Together, our data demonstrate that Gpr48 regulates bone formation
      and remodeling through the cAMP-PKA-Atf4 signaling pathway.

PMID- 19605505
TI  - Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI
      and CCI in a core dataset of 419 patients of the Austrian MDS Study Group.
AB  - BACKGROUND: The evaluation of comorbidity is of increasing importance in patients
      with hematologic disorders. PATIENTS AND METHODS: In the present study, the
      influence of comorbidity on survival and acute myeloid leukemia (AML) evolution
      was analyzed retrospectively in 419 patients with de novo myelodysplastic
      syndromes (MDS) (observation period: 1985-2007). The median age was 71 years
      (range 24-91 years). Two different scoring systems, the hematopoietic stem-cell
      transplantation-specific comorbidity index (HCT-CI) and the Charlson comorbidity
      index (CCI) were applied. RESULTS: The HCT-CI was found to be a significant
      prognostic factor for overall survival (OS, P < 0.05) as well as event-free
      survival (EFS, P < 0.05) in our patients, whereas the CCI was of prognostic
      significance for OS (P < 0.05), but not for EFS. For AML-free survival, neither
      the HCT-CI nor the CCI were of predictive value. A multivariate analysis
      including age, lactate dehydrogenase, ferritin, karyotype, number of cytopenias,
      French-American-British groups, and comorbidity was applied. Comorbidity was
      found to be an independent prognostic factor in patients with low- or int-1-risk
      MDS (P < 0.05) regarding OS and EFS. CONCLUSIONS: Together, our data show that
      comorbidity is an important risk factor for OS and EFS in patients with MDS.

PMID- 19605506
TI  - A phase II study of pemetrexed as second-line chemotherapy for the treatment of
      metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03
      67.
AB  - BACKGROUND: No standard therapy exists for post-docetaxel castrate-resistant
      prostate cancer (CRPC) patients. This trial aimed to determine the safety and
      efficacy of pemetrexed in post-docetaxel CRPC patients. MATERIALS AND METHODS:
      CRPC patients with progression after docetaxel (Taxotere) therapy received
      pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate
      specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate
      carrier-1 gene (RFC1) G80A polymorphism was also carried out. RESULTS: Forty-nine
      patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and
      median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20
      (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred
      in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%).
      A significant relationship was observed between time from prior docetaxel therapy
      and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies
      showed no relationship between genotypes and clinical efficacy. CONCLUSIONS:
      Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with
      only modest clinical activity. Further investigation of pemetrexed as a single
      agent in a nonenriched CRPC population is unlikely to add significant clinical
      benefit over that seen with traditional second-line chemotherapy agents such as
      mitoxantrone.

PMID- 19605507
TI  - A phase II dose-ranging study of palonosetron in Japanese patients receiving
      moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide
      based chemotherapy.
AB  - BACKGROUND: The 5-HT(3) receptor antagonists (RAs) help maintain the standard of
      care, in various combinations with other agents, for prevention of chemotherapy
      induced nausea and vomiting (CINV). Palonosetron is a new generation 5-HT(3) RA
      with indication not only acute but also delayed nausea and vomiting induced by
      moderately emetogenic chemotherapy (MEC). This study was carried out to determine
      the optimal dosage of palonosetron in combination with dexamethasone in patients
      in Japan. PATIENTS AND METHODS: This study evaluated the efficacy and safety of
      palonosetron in patients receiving MEC combined with dexamethasone. Patients
      received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC.
      Dexamethasone was infused before palonosetron, at 20 mg for the patients
      receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel.
      The primary end point was complete response (CR: no emetic episodes and no rescue
      medication) in the acute phase (0-24 h). RESULTS: In total, 204 patients (88 men,
      116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for
      efficacy. No dose-response relationship was observed regarding the CR rate in the
      acute phase. CR rates increased dose dependently for delayed (24-120 h) and
      overall (0-120 h) phases in patients receiving anthracyclines and
      cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates
      among doses was not statistically significant. The most commonly reported adverse
      events related to palonosetron were constipation and headache, confirming the
      class safety profile. CONCLUSION: This study indicates a statistically
      nonsignificant trend for the dose-response relationship for antiemetic protection
      in the delayed and overall phases in AC/EC patients (the regimen currently
      considered to be more emetogenic than MEC).

PMID- 19605508
TI  - Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in
      persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO
      (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies)
      Group.
AB  - BACKGROUND: The objective of the study was to estimate the antitumor activity of
      pemetrexed in patients with advanced/recurrent carcinoma of the cervix and to
      determine the nature and degree of toxicity. METHODS: A multicenter phase II
      trial was conducted by the Multicentre Italian Trials in Ovarian Cancer and
      Gynecologic Malignancies (MITO) Group. Patients with advanced/recurrent
      measurable carcinoma of the cervix that had failed one prior chemotherapy regimen
      in association or not with radiotherapy were treated with pemetrexed at a dose of
      500 mg/m(2) every 21 days. All the patients had a measurable lesion according to
      RECIST criteria in a not previously irradiated field. RESULTS: From November 2006
      to September 2008, 43 patients were entered by seven member institutions of the
      MITO-Group. A total of 164 cycles (median 2, range 1-9) were administered. The
      treatment was well tolerated. More serious toxic effects (grades 3 and 4)
      included leukopenia in 27.9% and neutropenia in 30.2% of patients. No treatment
      related deaths were reported. Six patients (13.9%) had partial responses (at
      least a 30% decrease in the sum of longest diameter of target lesions taking as
      reference the baseline sum longest diameter) with a median response of 7 weeks
      (range 3-27). Twenty-three patients (53.4%) had stable disease (less than a 50%
      reduction and less than a 25% increase in the sum of the products of two
      perpendicular diameters of all measured lesions and the appearance of no new
      lesions) and fourteen (32.5%) patients had progressive disease. Median
      progression-free survival was 10 weeks and overall survival was 35 weeks.
      CONCLUSION: Pemetrexed showed moderate activity against advanced/recurrent
      cervical cancer that had failed prior chemotherapy.

PMID- 19605509
TI  - Phase I study of apoptosis gene modulation with oblimersen within preoperative
      chemotherapy in patients with primary breast cancer.
AB  - Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated
      apoptotic signals in patients with breast cancer. We investigated effects of Bcl
      2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in
      breast tumor biopsies. Oblimersen targets Bcl-2 messenger RNA (mRNA), down
      regulates Bcl-2 protein translation and enhances antitumor effects of
      subtherapeutic chemotherapy doses. Within a phase I trial, we administered
      escalating doses of oblimersen (3, 5 or 7 mg/kg/day) as continuous infusion on
      days 1-7 in combination with standard-dose docetaxel (Taxotere), Adriamycin and
      cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with
      T2-4 tumors. Effects of oblimersen were evaluated in tumor biopsies and
      peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen and
      before TAC treatment by quantitative microfluidic real-time PCR. Read-outs
      consisted in measurement of Bcl-2 mRNA modulations and of 18 putative predictive
      markers. Two of 13 patients showed a diminution of Bcl-2 transcripts after 4 days
      of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a
      surrogate tissue because no qualified RNA could be isolated. Nevertheless, we
      demonstrated feasibility to process clinical samples and to obtain good quality
      RNA from tumor biopsies and indicated the potential of oblimersen to lower Bcl-2
      mRNA in breast cancer.

PMID- 19605510
TI  - Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non
      seminomatous germ-cell tumors.
AB  - BACKGROUND: Patients with elevated human chorionic gonadotrophin (HCG) can have
      hyperthyroidism. We assessed the prevalence of hyperthyroidism in patients
      presenting with disseminated non-seminomatous germ-cell tumors (NSGCT). PATIENTS
      AND METHODS: In all patients with metastatic NSGCT who started chemotherapy at
      our center from April 2001 to April 2007, thyroid function was analyzed. The
      association between thyroid function and HCG level was examined and the frequency
      of hyperthyroidism in patients with low (<5000 IU/l), intermediate (> or = 5000
      but <50 000 IU/l) and high (> or = 50 000 IU/l) serum HCG was assessed. RESULTS:
      For 144 of 148 eligible patients, thyroid function tests were available. Five
      patients with hyperthyroidism (3.5%) were identified, who all had high-serum HCG
      (mean 1 325 147 IU/l). Fifty percent of the patients with high HCG levels had
      hyperthyroidism versus 0% of the patients with HCG <50 000 IU/l (P < 0.001). Free
      thyroxin levels normalized within 26 days after starting chemotherapy in all
      patients. CONCLUSIONS: Hyperthyroidism frequently accompanies NSGCT with highly
      elevated HCG. Since its symptoms overlap with those of extensive metastatic
      disease, it may not be recognized. Thyroid function should be assessed in
      patients with high HCG levels and symptomatic hyperthyroidism should be treated
      temporarily with beta-blockade or antithyroidal medication.

PMID- 19605511
TI  - Prognostic impact of age and gender in 897 untreated patients with primary
      myelodysplastic syndromes.
AB  - BACKGROUND: The International Prognostic Scoring System (IPSS) is the golden
      standard to assess prognosis in myelodysplastic syndromes (MDS). The aim of this
      analysis was to study age and gender as interacting variables for individualized
      prognostication. PATIENTS AND METHODS: In all, 897 patients with primary MDS
      treated with supportive care only were examined in a retrospective multicenter
      study. A Cox model was developed to determine the prognostic impact of age and
      gender on survival and to examine their modulating influence on IPSS results.
      Based on main effects and interactions of these variables, we established an
      individualized age- and gender-adapted scoring system to improve prognostication
      in MDS. RESULTS: While the risk of a patient in the IPSS is best represented by
      the values 0 (low), +1 (intermediate-1), +2 (intermediate-2), and +3 (high),
      these values were found to vary between -1.9 and +3.5 in the same patients when
      including age and gender. Whereas in low-risk MDS, male patients were found to
      have a less favorable survival, a particularly high risk (+3.5) was found in
      younger (< or = 66 years) high-risk female patients. CONCLUSION: The inclusion of
      age and gender and their respective interactions contribute to improved and
      individualized prognostication in MDS.

PMID- 19605512
TI  - The genetics of induced pluripotency.
AB  - The flurry of recent publications regarding reprogramming of mature cell types to
      induced pluripotent stem cells raises the question: what exactly is pluripotency?
      A functional definition is provided by examination of the developmental potential
      of pluripotent stem cell types. Defining pluripotency at the molecular level,
      however, can be a greater challenge. Here, we examine the emerging list of genes
      associated with induced pluripotency, with particular attention to their
      functional requirement in the mouse embryo. Knowledge of the requirement for
      these genes in the embryo and in embryonic stem cells will advance our
      understanding of how to reverse the developmental clock for therapeutic benefit.

PMID- 19605513
TI  - Ovarian cancer risk factors in African-American and white women.
AB  - Ovarian cancer is the most lethal gynecologic malignancy in both African-American
      and white women. Although prevalences of many ovarian cancer risk factors differ
      markedly between African Americans and whites, there has been little research on
      how the relative contributions of risk factors may vary between racial/ethnic
      groups. Using data from a North Carolina case-control study (1999-2008), the
      authors conducted unconditional logistic regression analyses to calculate odds
      ratios and 95% confidence intervals for ovarian cancer risk factors in African
      American (143 cases, 189 controls) and white (943 cases, 868 controls) women and
      to test for interactions by race/ethnicity. They also calculated attributable
      fractions within each racial/ethnic group for the modifiable factors of
      pregnancy, oral contraceptive use, tubal ligation, and body mass index. Many risk
      factors showed similar relations across racial/ethnic groups, but tubal ligation
      and family history of breast or ovarian cancer showed stronger associations among
      African Americans. Younger age at menarche was associated with risk only in white
      women. Attributable fractions associated with tubal ligation, oral contraceptive
      use, and obesity were markedly higher for African Americans. The relative
      importance of ovarian cancer risk factors may differ for African-American women,
      but conclusions were limited by the small sample. There is a clear need for
      further research on etiologic factors for ovarian cancer in African-American
      women.

PMID- 19605515
TI  - Re: "Red meat and chicken consumption and its association with age-related
      macular degeneration".

PMID- 19605514
TI  - Trajectories of cognitive function in late life in the United States: demographic
      and socioeconomic predictors.
AB  - This study used mixed-effects modeling of data from a national sample of 6,476 US
      adults born before 1924, who were tested 5 times between 1993 and 2002 on word
      recall, serial 7's, and other mental status items to determine demographic and
      socioeconomic predictors of trajectories of cognitive function in older
      Americans. Mean decline with aging in total cognition score (range, 0-35;
      standard deviation, 6.00) was 4.1 (0.68 standard deviations) per decade (95%
      confidence interval: 3.8, 4.4) and in recall score (range, 0-20; standard
      deviation, 3.84) was 2.3 (0.60 standard deviations) per decade (95% confidence
      interval: 2.1, 2.5). Older cohorts (compared with younger cohorts), women
      (compared with men), widows/widowers, and those never married (both compared with
      married individuals) declined faster, and non-Hispanic blacks (compared with non
      Hispanic whites) and those in the bottom income quintile (compared with the top
      quintile) declined slower. Race and income differences in rates of decline were
      not sufficient to offset larger differences in baseline cognition scores.
      Educational level was not associated with rate of decline in cognition scores.
      The authors concluded that ethnic and socioeconomic disparities in cognitive
      function in older Americans arise primarily from differences in peak cognitive
      performance achieved earlier in the life course and less from declines in later
      life.

PMID- 19605516
TI  - Re: "Long-term use of beta-carotene, retinol, lycopene, and lutein supplements
      and lung cancer risk: results from the VITamins and Lifestyle (VITAL) Study".

PMID- 19605518
TI  - Web-based tools and approaches to study long-range gene regulation in Metazoa.
AB  - Regulatory elements can affect specific genes from megabase distances, often from
      within or beyond unrelated neighbouring genes. The task of computational charting
      of regulatory inputs in the genome can be approached from several directions.
      Typically, computational identification of putative regulatory elements for a
      gene of interest requires tools that will aid in estimating the extent of the
      (potentially vast) genomic region around the gene that is likely to contain
      regulatory elements, as well as tools for the identification and characterization
      of individual elements. Conversely, starting from a putative regulatory element
      or a regulatory variation in a non-coding region, one often wants to associate
      the regulatory element with the correct target gene(s). The design of tools for
      these purposes relies on the remarkably high level of sequence conservation of
      thousands of regulatory enhancers, their strong tendency to cluster around their
      target genes, as well as a constrained range of functional categories of the
      corresponding target genes, many of which are developmental regulators.
      Additional evolutionary information, such as conservation of synteny, and a
      growing body of functional genomic and epigenomic data are being rapidly added to
      established and emerging tools for studying developmental regulation and cross
      species conservation to provide new functional insights into the roles of these
      regions. In this article, we give an overview of the functionality available in
      general purpose and new/specialized web tools for the above tasks, and discuss
      current and future developments in the field.

PMID- 19605519
TI  - The role of dopamine in the prelimbic cortex and the dorsomedial striatum in
      instrumental conditioning.
AB  - The prelimbic (PL) region of the prefrontal cortex and the posterior subregion of
      the dorsomedial striatum (pDMS) are components of a corticostriatal circuit
      subserving instrumental learning. Here, we examined whether dopamine (DA) signals
      conveyed to the PL and pDMS are critical for instrumental learning. Rats with 6
      hydroxydopamine or vehicle infusion into the PL and pDMS were trained to press 2
      levers, either for food pellets or a sucrose solution. Thereafter, we tested
      whether the animals were sensitive 1) to a selective degradation of 1 of 2
      outcomes using a specific satiety procedure and 2) to a selective degradation of
      1 of 2 contingencies controlling instrumental behavior. Rats with PL DA depletion
      displayed a reduced rate of lever presses but appeared to be sensitive to outcome
      devaluation and contingency degradation. Thus, PL DA seems to modulate lever
      pressing but does not support instrumental conditioning. In contrast, rats with
      pDMS DA depletion had intact response rates and were sensitive to selective
      outcome devaluation; however, they showed a reduced sensitivity to contingency
      degradation. Therefore, pDMS DA signaling seems not to be involved in maintaining
      lever pressing but instead contributes to instrumental conditioning by supporting
      the detection of causal relationships between an action and its consequences.

PMID- 19605520
TI  - Overlapping and distinct neural representations of numbers and verbal transitive
      series.
AB  - It is a familiar and intuitive notion that human numerical and logical reasoning
      skills are tightly related. However, very little is known about the interaction
      between numerical knowledge and logical reasoning in the brain. Using functional
      magnetic resonance imaging in healthy subjects, we investigated ordered relations
      as they are expressed in number (4 is greater than 2) and in transitive reasoning
      (A is to the left of C after receiving; A is to the left of B; B is to the left
      of C) in order to determine the extent to which the same neural substrates
      support both. We found that representing an ordered series verbally learned by
      transitive reasoning draws on the representations of numbers in the anterior
      intraparietal sulcus. We further observed that, unlike numbers, transitive series
      are additionally encoded in the basal ganglia-dopamine system. Intraparietal and
      basal ganglia mechanisms are not active to the same extent at the same time.
      Although the intraparietal representations of number preferentially supports a
      verbal transitive series soon after learning, the basal ganglia are engaged when
      the series is well practiced. This finding suggests that the transient activation
      of number representations supports the representation of verbal transitive series
      until their late encoding in the basal ganglia-dopamine system by associative
      reinforcement mechanisms.

PMID- 19605517
TI  - Dysfunction of a cortical midline network during emotional appraisals in
      schizophrenia.
AB  - A cardinal feature of schizophrenia is the poor comprehension, or
      misinterpretation, of the emotional meaning of social interactions and events,
      which can sometimes take the form of a persecutory delusion. It has been shown
      that the comprehension of the emotional meaning of the social world involves a
      midline paralimbic cortical network. However, the function of this network during
      emotional appraisals in patients with schizophrenia is not well understood. In
      this study, hemodynamic responses were measured in 14 patients with schizophrenia
      and 18 healthy subjects during the evaluation of descriptions of social
      situations with negative, positive, and neutral affective valence. The healthy
      and schizophrenia groups displayed opposite patterns of responses to emotional
      and neutral social situations within the medial prefrontal and posterior
      cingulate cortices--healthy participants showed greater activity to the emotional
      compared to the neutral situations, while patients exhibited greater responses to
      the neutral compared to the emotional situations. Moreover, the magnitude of the
      response within bilateral cingulate gyri to the neutral social stimuli predicted
      delusion severity in the patients with schizophrenia. These findings suggest that
      impaired functioning of cortical midline structures in schizophrenia may underlie
      faulty interpretations of social events, contributing to delusion formation.

PMID- 19605521
TI  - A 1H-MR spectroscopy study of changes in glutamate and glutamine (Glx)
      concentrations in frontal spectra after administration of memantine.
AB  - Glutamate is the major excitatory neurotransmitter in the brain and therefore
      important for cognitive functions. The aim of the study was to investigate if
      administration of the N-methyl-D-aspartate receptor antagonist memantine to
      healthy individuals would affect brain activation when performing an auditory
      attention task. The task was a variant of a dichotic listening task with
      different instructions that tap demands for attention and cognitive control. We
      asked the question if memantine administration would lead to reduction in
      glutamatergic neurotransmission in areas related to attention and cognitive
      control. Left and right frontal glutamate and glutamine (Glx) concentrations were
      measured, using (1)H-MR spectroscopy. Twenty-five healthy adults were scanned
      twice in a counterbalanced design, either drug naive or after administration of
      memantine for 21 days. The results showed that memantine significantly reduced
      Glx concentrations, and this reduction was associated with a reduction in brain
      activation in prefrontal cortex, which could have implications for understanding
      the neuronal mechanisms underlying higher cognitive functions such as cognitive
      control.

PMID- 19605522
TI  - Mutant 5-hydroxytryptamine 1A receptor D116A is a receptor activated solely by
      synthetic ligands with a rich pharmacology.
AB  - Like other biogenic amine G protein-coupled receptors, mutation of the conserved
      aspartatic residue into alanine at position 116 (D116A(3.32)) in the 5
      hydroxytryptamine (5-HT)(1A) receptor greatly affects 5-HT binding and signal
      transduction. [(3)H]8-Hydroxy-2-dipropylaminotetralin (8-OH-DPAT) and [(3)H]-N-(2
      (4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
      trihydrochloride (WAY100,635) are capable to bind the 5-HT(1A)-D116A mutant and,
      using these radioligands, we show here that this mutation dramatically reduces
      the affinities of the selective 5-HT(1A) agonists N-(3-chloro-4-fluorobenzoyl)-4
      fluoro-4-[(5-methylpyridin-2-yl)-methylamino methyl]piperidine (F13640), 3-chloro
      4-fluorophenyl-(4-fluorophenyl-4-{[(5-methyl-6 methylamino-pyridin-2-ylmethyl)
      amino]-methyl}-piperidin-1-yl-methanone (F13714), and 2-[5-[3-(4
      methylsulfonylamino)benzyl-1,4-oxadiazol-5-yl]-1H-indole-3-yl]ethylamine
      (L694247) and that of 5-carboxamidotryptamine. Although to a lesser extent, the
      binding of buspirone, (+)-flesinoxan, (-)-pindolol, and (-)-8-OH-DPAT are also
      highly decreased. In contrast, affinities of the 5-HT(1A) ligands WAY100,635,
      spiperone, (-)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz {c,d}indole-6-carboxamide
      (LY228,729), and 1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphtyl)
      piperazine (S14506) and the prototypical 5-HT(1A) agonist (+)-8-OH-DPAT are only
      slightly affected by the mutation, suggesting a moderate contribution of Asp116
      to the binding pocket for these latter. Furthermore, LY228,729, S14506, and (+)-8
      OH-DPAT induce a potent and efficacious coupling of the 5-HT(1A)-D116A receptor
      to G protein activation as measured by Ca(2+) mobilization and guanosine 5'-O-(3
      [(35)S]thio)triphosphate binding in Chinese hamster ovary cells as well as by G
      protein-coupled inwardly rectifying potassium channel current activation in
      Xenopus laevis oocytes. It is interesting that the selective 5-HT(1A) antagonist
      WAY100,635 shows potent partial agonist activity at the 5-HT(1A)-D116A mutant,
      whereas spiperone maintains its inverse agonist properties. The pharmacological
      approach reported here re-evaluates the binding and functional properties of the
      5-HT(1A)-D116A receptor and describes for the first time this mutant as a
      receptor activated solely by synthetic ligands (RASSL), with a rich pharmacology.
      By bioengineering animal models incorporating this RASSL, one may further explore
      the role of 5-HT(1A) receptor signaling in the central nervous system as well as
      G(i) protein-mediated signaling pathways in other tissues.

PMID- 19605523
TI  - Coordinated regulation of dimethylarginine dimethylaminohydrolase-1 and cationic
      amino acid transporter-1 by farnesoid X receptor in mouse liver and kidney and
      its implication in the control of blood levels of asymmetric dimethylarginine.
AB  - Asymmetric dimethylarginine (ADMA) is a potent endogenous inhibitor of
      endothelial nitric-oxide synthase (eNOS), and increased plasma concentrations of
      ADMA have been regarded as a risk factor for a number of cardiovascular diseases.
      Circulating ADMA is largely taken up by liver and kidney via system y(+) carriers
      of the cationic amino acid (CAT) family and subsequently metabolized by
      dimethylarginine dimethylaminohydrolases (DDAHs). As such, agents targeted at
      enhancing ADMA metabolism may prove to be useful in the prevention and/or
      treatment of various types of cardiovascular disease. Farnesoid X receptor (FXR)
      is a member of the nuclear receptor superfamily and plays an important role in
      the maintenance of cholesterol and bile acid homeostasis. We report here that
      treatment of mice with an FXR agonist 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2
      chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole; GW4064) led to increased
      expression of DDAH-1 and CAT-1 in both liver and kidney. In cultured human
      hepatocytes and kidney proximal tubular epithelial cells, GW4064 increased CAT-1
      expression, and this was associated with a significant increase in the cellular
      uptake of ADMA. Promoter analyses suggest that CAT-1 is a likely target of FXR,
      and a functional FXR response element was found in the promoter region of CAT-1
      gene. These data suggest that FXR may play an important role in regulating blood
      levels of ADMA via coordinated regulation of DDAH-1 and CAT-1 in liver and
      kidney.

PMID- 19605524
TI  - Agonist-biased signaling via proteinase activated receptor-2: differential
      activation of calcium and mitogen-activated protein kinase pathways.
AB  - We evaluated the ability of different trypsin-revealed tethered ligand (TL)
      sequences of rat proteinase-activated receptor 2 (rPAR(2)) and the corresponding
      soluble TL-derived agonist peptides to trigger agonist-biased signaling. To do
      so, we mutated the proteolytically revealed TL sequence of rPAR(2) and examined
      the impact on stimulating intracellular calcium transients and mitogen-activated
      protein (MAP) kinase. The TL receptor mutants, rPAR(2)-Leu(37)Ser(38), rPAR(2)
      Ala(37-38), and rPAR(2)-Ala(39-42) were compared with the trypsin-revealed wild
      type rPAR(2) TL sequence, S(37)LIGRL(42)-. Upon trypsin activation, all
      constructs stimulated MAP kinase signaling, but only the wt-rPAR(2) and rPAR(2)
      Ala(39-42) triggered calcium signaling. Furthermore, the TL-derived synthetic
      peptide SLAAAA-NH2 failed to cause PAR(2)-mediated calcium signaling but did
      activate MAP kinase, whereas SLIGRL-NH2 triggered both calcium and MAP kinase
      signaling by all receptors. The peptides AAIGRL-NH2 and LSIGRL-NH2 triggered
      neither calcium nor MAP kinase signals. Neither rPAR(2)-Ala(37-38) nor rPAR(2)
      Leu(37)Ser(38) constructs recruited beta-arrestins-1 or -2 in response to trypsin
      stimulation, whereas both beta-arrestins were recruited to these mutants by
      SLIGRL-NH2. The lack of trypsin-triggered beta-arrestin interactions correlated
      with impaired trypsin-activated TL-mutant receptor internalization. Trypsin
      stimulated MAP kinase activation by the TL-mutated receptors was not blocked by
      inhibitors of Galpha(i) (pertussis toxin), Galpha(q) [N-cyclohexyl-1-(2,4
      dichlorophenyl)-1,4-dihydro-6-methylindeno[1,2-c]pyrazole-3-carboxamide (GP2A)],
      Src kinase [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine
      (PP1)], or the epidermal growth factor (EGF) receptor [4-(3'-chloroanilino)-6,7
      dimethoxy-quinazoline (AG1478)], but was inhibited by the Rho-kinase inhibitor
      (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, 2HCl
      (Y27362). The data indicate that the proteolytically revealed TL sequence(s) and
      the mode of its presentation to the receptor (tethered versus soluble) can confer
      biased signaling by PAR(2), its arrestin recruitment, and its internalization.
      Thus, PAR(2) can signal to multiple pathways that are differentially triggered by
      distinct proteinase-revealed TLs or by synthetic signal-selective activating
      peptides.

PMID- 19605526
TI  - Undernourished children have different temperaments than better-nourished
      children in rural Bangladesh.
AB  - Undernutrition in early childhood is associated with poor cognitive development
      and some changes in behavior. However, there is little information on their
      temperament. Our objective in this study was to determine whether undernourished
      children aged 6-24 mo had different temperament traits than better-nourished
      children. Two hundred and twelve undernourished children (weight for age < -2 Z
      scores) attending community nutrition centers in 20 villages in rural Bangladesh
      and 108 better-nourished children (weight-for-age > or = -2 Z-scores) matched for
      age, sex, and village participated in the study. Temperament was assessed through
      an interviewer-administered maternal questionnaire consisting of 7 subscales:
      manageability, activity, emotionality, sociability, attention, soothability, and
      fear. After adjusting for significant covariates, the undernourished children
      were less sociable [regression coefficient (B) = -0.96; 95% CI = -0.04, -1.88],
      less attentive (B = -0.94; 95% CI = -0.19, -1.69), more fearful (B = 1.43; 95% CI
      = 2.44, 0.42), and had more negative emotionality (B = -1.08; 95% CI = 0.006, 
      2.16). In conclusion, these undernourished children had comprehensive differences
      in temperament traits, which may increase their risk of developing behavioral and
      mental health problems in later childhood.

PMID- 19605525
TI  - Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth
      muscle ion channels may account for differences in cardiovascular risk profiles.
AB  - Celecoxib, rofecoxib, and diclofenac are clinically used cyclooxygenase-2 (COX-2)
      inhibitors, which have been under intense scrutiny because long-term rofecoxib
      (Vioxx; Merck, Whitehouse Station, NJ) treatment was found to increase the risk
      of adverse cardiovascular events. A differential risk profile for these drugs has
      emerged, but the underlying mechanisms have not been fully elucidated. We
      investigated the effects of celecoxib, rofecoxib, and diclofenac on ionic
      currents and calcium signaling in vascular smooth muscle cells (VSMCs) using
      patch-clamp techniques and fura-2 fluorescence and on arterial constriction using
      pressure myography. Celecoxib, but not rofecoxib or diclofenac, dramatically
      enhanced KCNQ (K(v)7) potassium currents and suppressed L-type voltage-sensitive
      calcium currents in A7r5 rat aortic smooth muscle cells (native KCNQ currents or
      overexpressed human KCNQ5 currents) and freshly isolated rat mesenteric artery
      myocytes. The effects of celecoxib were concentration-dependent within the
      therapeutic concentration range, and were reversed on washout. Celecoxib, but not
      rofecoxib, also inhibited calcium responses to vasopressin in A7r5 cells and
      dilated intact or endothelium-denuded rat mesenteric arteries. A celecoxib
      analog, 2,5-dimethyl-celecoxib, which does not inhibit COX-2, mimicked celecoxib
      in its enhancement of vascular KCNQ5 currents, suppression of L-type calcium
      currents, and vasodilation. We conclude that celecoxib inhibits calcium responses
      in VSMCs by enhancing KCNQ5 currents and suppressing L-type calcium currents,
      which ultimately reduces vascular tone. These effects are independent of its COX
      2 inhibitory actions and may explain the differential risk of cardiovascular
      events in patients taking different drugs of this class.

PMID- 19605527
TI  - Nonglucose carbohydrates and infant nutrition and metabolism.

PMID- 19605528
TI  - Soy protein reduces serum LDL cholesterol and the LDL cholesterol:HDL cholesterol
      and apolipoprotein B:apolipoprotein A-I ratios in adults with type 2 diabetes.
AB  - Type 2 diabetes is highly prevalent in North America and is associated with
      increased risk of cardiovascular disease (CVD). Evidence supports a role for soy
      protein in the reduction of serum lipids related to CVD risk; however, few
      studies have focused on adults with type 2 diabetes who are not on lipid-lowering
      medications and/or do not have diabetic complications. The purpose of this study
      was to determine the effect of soy protein isolate (SPI) consumption on serum
      lipids in adults with diet-controlled type 2 diabetes. Using a double-blind,
      randomized, crossover, placebo-controlled intervention study design, adults with
      diet-controlled type 2 diabetes (n = 29) consumed SPI (80 mg/d aglycone
      isoflavones) or milk protein isolate (MPI) for 57 d each separated by a 28-d
      washout period. Twenty-four-hour urine samples were collected on d 54-56 of each
      treatment for analysis of isoflavones and blood was collected on d 1 and 57 of
      each treatment and analyzed for serum lipids and apolipoproteins. SPI consumption
      increased urinary isoflavones compared with MPI. SPI consumption reduced serum
      LDL cholesterol (P = 0.04), LDL cholesterol:HDL cholesterol (P = 0.02), and
      apolipoprotein B:apolipoprotein A-I (P = 0.05) compared with MPI. SPI did not
      affect serum total cholesterol, HDL cholesterol, triacylglycerol, apolipoprotein
      B, or apolipoprotein A-I. These data demonstrate that consumption of soy protein
      can modulate some serum lipids in a direction beneficial for CVD risk in adults
      with type 2 diabetes.

PMID- 19605529
TI  - Soluble fiber viscosity affects both goblet cell number and small intestine mucin
      secretion in rats.
AB  - We examined the role of soluble fiber viscosity in small intestinal mucin
      secretion. Viscosities were defined as the area under the viscosity curve (VAUC).
      Rats were fed a control diet or diets containing konjac mannan (KM) [low, medium,
      or high molecular weight (LKM, MKM, HKM), respectively] at 50 g/kg diet for 10 d.
      Luminal mucin content and goblet cell number increased in proportion to the
      molecular weight of KM. Such effects with the HKM diet were nullified by the
      concurrent ingestion of 2 g cellulase/kg diet. Diet containing LKM, MKM, HKM,
      guar gums (high or low molecular weight; HGG, LGG), psyllium (PS), or pectin (PC)
      at 50 g/kg was fed to rats. Fibers with higher VAUC (MKM, HKM, HGG, and PS)
      increased goblet cell numbers, but not those with lower VAUC (LKM, LGG, and PC).
      Luminal mucins were greater in rats fed HKM, PC, and PS diets. Goblet cell
      numbers and VAUC were correlated (r = 0.98; P < 0.01). In rats fed the HKM diet,
      ileal Muc2 gene expression was not affected, but that of Muc3 was lower than in
      those fed the control diet, indicating that the increase in luminal mucins after
      ingestion of HKM diet occurred independently of enhanced Muc gene expression. An
      incorporation study of 5'-bromo-deoxyuridine (BrdU) showed the position of the
      uppermost-BrdU labeled cell along the villi was higher in rats fed the HKM diet
      than in those fed the control diet. The results suggest that soluble fibers,
      except PC, upregulate baseline secretion of luminal mucins by increasing goblet
      cell numbers in proportion to fiber VAUC.

PMID- 19605530
TI  - Modulation of fusiform cortex activity by cholinesterase inhibition predicts
      effects on subsequent memory.
AB  - Cholinergic influences on memory are likely to be expressed at several processing
      stages, including via well-recognized effects of acetylcholine on stimulus
      processing during encoding. Since previous studies have shown that cholinesterase
      inhibition enhances visual extrastriate cortex activity during stimulus encoding,
      especially under attention-demanding tasks, we tested whether this effect
      correlates with improved subsequent memory. In a within-subject physostigmine
      versus placebo design, we measured brain activity with functional magnetic
      resonance imaging while healthy and mild Alzheimer's disease subjects performed
      superficial and deep encoding tasks on face (and building) visual stimuli. We
      explored regions in which physostigmine modulation of face-selective neural
      responses correlated with physostigmine effects on subsequent recognition
      performance. In healthy subjects physostigmine led to enhanced later recognition
      for deep- versus superficially-encoded faces, which correlated across subjects
      with a physostigmine-induced enhancement of face-selective responses in right
      fusiform cortex during deep- versus superficial-encoding tasks. In contrast, the
      Alzheimer's disease group showed neither a depth of processing effect nor
      restoration of this with physostigmine. Instead, patients showed a task
      independent improvement in confident memory with physostigmine, an effect that
      correlated with enhancements in face-selective (but task-independent) responses
      in bilateral fusiform cortices. Our results indicate that one mechanism by which
      cholinesterase inhibitors can improve memory is by enhancing extrastriate cortex
      stimulus selectivity at encoding, in a manner that for healthy people but not in
      Alzheimer's disease is dependent upon depth of processing.

PMID- 19605531
TI  - ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for
      mitoxantrone response in multiple sclerosis.
AB  - Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is
      limited by partially dose-dependent side-effects. Predictors of therapeutic
      response may result in individualized risk stratification and MX dosing. ATP
      binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance
      mechanisms involved in active cellular MX efflux. Here, we investigated the role
      of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response,
      corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1
      2677G>T, 3435C>T and five ABCG2-SNPs were analysed in 832 multiple sclerosis
      patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in
      vitro assay, MX efflux in leukocytes from individuals with variant alleles in
      both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2% of patients) was
      37.7% lower than from individuals homozygous for common alleles (ABCB1/ABCG2
      H(igh), P < 0.05, 14.8% of patients), resulting in genotype-dependent MX
      accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX
      efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets,
      glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially
      affected by MX therapy. In vivo significance was further corroborated in
      experimental autoimmune encephalomyelitis in Abcg2(-/-) animals. Using a MX dose
      titrated to be ineffective in wild-type animals, disease course and
      histopathology in Abcg2(-/-) mice were strongly ameliorated. Retrospective
      clinical analysis in MX monotherapy patients (n = 155) used expanded disability
      status scale, relapse rate and multiple sclerosis functional composite as major
      outcome parameters. The clinical response rate [overall 121 of 155 patients
      (78.1%)] increased significantly with genotypes associated with decreasing
      ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5%) responders, ABCB1/ABCG2
      I(ntermediate) 78/98 (79.6%), ABCB1/ABCG2-L 28/33 (84.8%), exact Cochran-Armitage
      test P = 0.039]. The odds ratio for response was 1.9 (95% CI 1.0-3.5) with each
      increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to -I-, and -I to -L). In 36
      patients with severe cardiac or haematological side effects no statistically
      relevant difference in genotype frequency was observed. However, one patient with
      biopsy proven cardiomyopathy only after 24 mg/m2 MX exhibited a rare genotype
      with variant, partly homozygous alleles in 3 ABC-transporter genes. In
      conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers
      associated with clinical response to MX therapy in multiple sclerosis. Combined
      MX/GC-treatment warrants further investigation.

PMID- 19605532
TI  - Distinct roles for sequences upstream of and downstream from Physarum editing
      sites.
AB  - RNAs in the mitochondria of Physarum polycephalum contain nonencoded nucleotides
      that are added during RNA synthesis. Essentially all steady-state RNAs are
      accurately and fully edited, yet the signals guiding these precise nucleotide
      insertions are presently unknown. To localize the regions of the template that
      are required for editing, we constructed a series of chimeric templates that
      substitute varying amounts of DNA either upstream of or downstream from C
      insertion sites. Remarkably, all sequences necessary for C addition are contained
      within approximately 9 base pairs on either side of the insertion site. In
      addition, our data strongly suggest that sequences within this critical region
      affect different steps in the editing reaction. Template alterations upstream of
      an editing site influence nucleotide selection and/or insertion, while downstream
      changes affect editing site recognition and templated extension from the added,
      unpaired nucleotide. The data presented here provide the first evidence that
      individual regions of the DNA template play discrete mechanistic roles and
      represent a crucial initial step toward defining the source of the editing
      specificity in Physarum mitochondria. In addition, these findings have
      mechanistic implications regarding the potential involvement of the mitochondrial
      RNA polymerase in the editing reaction.

PMID- 19605533
TI  - A long-range RNA-RNA interaction between the 5' and 3' ends of the HCV genome.
AB  - The RNA genome of the hepatitis C virus (HCV) contains multiple conserved
      structural cis domains that direct protein synthesis, replication, and
      infectivity. The untranslatable regions (UTRs) play essential roles in the HCV
      cycle. Uncapped viral RNAs are translated via an internal ribosome entry site
      (IRES) located at the 5' UTR, which acts as a scaffold for recruiting multiple
      protein factors. Replication of the viral genome is initiated at the 3' UTR.
      Bioinformatics methods have identified other structural RNA elements thought to
      be involved in the HCV cycle. The 5BSL3.2 motif, which is embedded in a cruciform
      structure at the 3' end of the NS5B coding sequence, contributes to the three
      dimensional folding of the entire 3' end of the genome. It is essential in the
      initiation of replication. This paper reports the identification of a novel,
      strand-specific, long-range RNA-RNA interaction between the 5' and 3' ends of the
      genome, which involves 5BSL3.2 and IRES motifs. Mutants harboring substitutions
      in the apical loop of domain IIId or in the internal loop of 5BSL3.2 disrupt the
      complex, indicating these regions are essential in initiating the kissing
      interaction. No complex was formed when the UTRs of the related foot and mouth
      disease virus were used in binding assays, suggesting this interaction is
      specific for HCV sequences. The present data firmly suggest the existence of a
      higher-order structure that may mediate a protein-independent circularization of
      the HCV genome. The 5'-3' end bridge may have a role in viral translation
      modulation and in the switch from protein synthesis to RNA replication.

PMID- 19605534
TI  - Association of substance use disorders with childhood trauma but not African
      genetic heritage in an African American cohort.
AB  - OBJECTIVE: Genetic variation influences differential vulnerability to addiction
      within populations. However, it remains unclear whether differences in
      frequencies of vulnerability alleles contribute to disparities between
      populations and to what extent ancestry correlates with differential exposure to
      environmental risk factors, including poverty and trauma. METHOD: The authors
      used 186 ancestry-informative markers to measure African ancestry in 407 addicts
      and 457 comparison subjects self-identified as African Americans. The reference
      group was 1,051 individuals from the Human Genome Diversity Cell Line Panel,
      which includes 51 diverse populations representing most worldwide genetic
      diversity. RESULTS: African Americans varied in degrees of African, European,
      Middle Eastern, and Central Asian genetic heritage. The overall level of African
      ancestry was actually smaller among cocaine, opiate, and alcohol addicts
      (proportion=0.76-0.78) than nonaddicted African American comparison subjects
      (proportion=0.81). African ancestry was associated with living in impoverished
      neighborhoods, a factor previously associated with risk. There was no association
      between African ancestry and exposure to childhood abuse or neglect, a factor
      that strongly predicted all types of addictions. CONCLUSIONS: These results
      suggest that African genetic heritage does not increase the likelihood of genetic
      risk for addictions. They highlight the complex interrelation between genetic
      ancestry and social, economic, and environmental conditions and the strong
      relation of those factors to addiction. Studies of epidemiological samples
      characterized for genetic ancestry and social, psychological, demographic,
      economic, cultural, and historical factors are needed to better disentangle the
      effects of genetic and environmental factors underlying interpopulation
      differences in vulnerability to addiction and other health disparities.

PMID- 19605535
TI  - Childhood motor coordination and adult schizophrenia spectrum disorders.
AB  - OBJECTIVE: The authors examined whether motor coordination difficulties assessed
      in childhood predict later adult schizophrenia spectrum outcomes. METHOD: A
      standardized childhood neurological examination was administered to a sample of
      265 Danish children in 1972, when participants were 10-13 years old. Adult
      diagnostic information was available for 244 members of the sample. Participants
      fell into three groups: children whose mothers or fathers had a psychiatric
      hospital diagnosis of schizophrenia (N=94); children who had at least one parent
      with a psychiatric record of hospitalization for a nonpsychotic disorder (N=84);
      and children with no parental records of psychiatric hospitalization (N=66).
      Psychiatric outcomes of the offspring were assessed through psychiatric
      interviews in 1992 when participants were 31-33 years of age, as well as through
      a scan of national psychiatric registers completed in May 2007. RESULTS: Children
      who later developed a schizophrenia spectrum disorder (N=32) displayed
      significantly higher scores on a scale of coordination deficits compared with
      those who did not develop a mental illness in this category (N=133). CONCLUSIONS:
      Results from this study provide further support for the neurodevelopmental
      hypothesis of schizophrenia and underscore the potential role of cerebellar
      and/or basal ganglia abnormalities in the etiology and pathophysiology of
      schizophrenia.

PMID- 19605536
TI  - A molecular signature of depression in the amygdala.
AB  - OBJECTIVE: Major depressive disorder is a heterogeneous illness with a mostly
      uncharacterized pathology. Recent gene array attempts to identify the molecular
      underpinnings of the illness in human postmortem subjects have not yielded a
      consensus. The authors hypothesized that controlling several sources of clinical
      and technical variability and supporting their analysis with array results from a
      parallel study in the unpredictable chronic mild stress (UCMS) rodent model of
      depression would facilitate identification of the molecular pathology of major
      depression. METHOD: Large-scale gene expression was monitored in postmortem
      tissue from the anterior cingulate cortex and amygdala in paired male subjects
      with familial major depression and matched control subjects without major
      depression (N=14-16 pairs). Area dissections and analytical approaches were
      optimized. Results from the major depression group were compared with those from
      the UCMS study and confirmed by quantitative polymerase chain reaction and
      Western blot. Gene coexpression network analysis was performed on transcripts
      with conserved major depression-UCMS effects. RESULTS: Significant and
      bidirectional predictions of altered gene expression were identified in amygdala
      between major depression and the UCMS model of depression. These effects were
      detected at the group level and also identified a subgroup of depressed subjects
      with a more homogeneous molecular pathology. This phylogenetically conserved
      "molecular signature" of major depression was reversed by antidepressants in
      mice, identified two distinct oligodendrocyte and neuronal phenotypes, and
      participated in highly cohesive and interactive gene coexpression networks.
      CONCLUSIONS: These studies demonstrate that the biological liability to major
      depression is reflected in a persistent molecular pathology that affects the
      amygdala, and support the hypothesis of maladaptive changes in this brain region
      as a putative primary pathology in major depression.

PMID- 19605537
TI  - Effects of catechol-O-methyltransferase on normal variation in the cognitive
      function of children.
AB  - OBJECTIVE: Genetic variants that contribute to the risk of psychiatric disorders
      may also affect normal variation in psychological function. Indeed, the
      behavioral effects of many genetic variants may be better understood as process
      specific rather than disease-specific. A functional valine-to-methionine
      (Val(158)Met) polymorphism in the catechol-O-methyltransferase (COMT) gene has
      been associated with cognitive function and brain metabolic activity accompanying
      such tasks. Not all studies are consistent, and less is known about the effect of
      this polymorphism during development. The authors tested the hypothesis that a
      more informative COMT haplotype predicts normal cognitive development in a large
      population-based cohort of children enrolled in the Avon Longitudinal Study of
      Parents and Children. METHOD: Effects on verbal and performance IQ as well as
      verbal inhibition were assessed at age 8, and effects on working memory were
      assessed at age 10. From the five COMT single nucleotide polymorphisms (SNPs)
      genotyped, the effect of a functional three-SNP haplotype consisting of
      Val(158)Met and two synonymous SNPs (rs6269 and rs4818), which together exert a
      major influence on the level of COMT expression and enzyme activity, was
      evaluated. RESULTS: This three-SNP haplotype predicted both verbal inhibition and
      working memory, and there was a genotype-by-sex interaction on verbal IQ. The
      effect of COMT genotype (diplotype) on cognition was curvilinear, which is
      consistent with the "inverted U" model of dopamine effect on frontal cortical
      efficiency. In addition, the SNP rs2075507 (previously rs2097603) was
      independently associated with verbal inhibition, while rs165599 showed no main
      cognitive effects. However, rs165599 showed a genotype-by-sex interaction with
      working memory. CONCLUSIONS: Genetic variation at several loci in the COMT gene
      affects normal cognitive function in children.

PMID- 19605538
TI  - Neuroanatomic alterations and social and communication deficits in monozygotic
      twins discordant for autism disorder.
AB  - OBJECTIVE: Investigating neuroanatomic differences in monozygotic twins who are
      discordant for autism can help unravel the relative contributions of genetics and
      environment to this pervasive developmental disorder. The authors used magnetic
      resonance imaging (MRI) to investigate several brain regions of interest in
      monozygotic twins who varied in degree of phenotypic discordance for narrowly
      defined autism. METHOD: The subjects were 14 pairs of monozygotic twins between
      the ages of 5 and 14 years old and 14 singleton age- and gender-matched typically
      developing comparison subjects. The monozygotic twin group was a cohort of
      children with narrowly defined autistic deficits and their co-twins who presented
      with varying levels of autistic deficits. High-resolution MRIs were acquired and
      volumetric/area measurements obtained for the frontal lobe, amygdala, and
      hippocampus and subregions of the prefrontal cortex, corpus callosum, and
      cerebellar vermis. RESULTS: No neurovolumetric/area differences were found
      between twin pairs. Relative to typically developing comparison subjects,
      dorsolateral prefrontal cortex volumes and anterior areas of the corpus callosum
      were significantly altered in autistic twins, and volumes of the posterior vermis
      were altered in both autistic twins and co-twins. Intraclass correlation analysis
      of brain volumes between children with autism and their co-twins indicated that
      the degree of within-pair neuroanatomic concordance varied with brain region. In
      the group of subjects with narrowly defined autism only, dorsolateral prefrontal
      cortex, amygdala, and posterior vermis volumes were significantly associated with
      the severity of autism based on scores from the Autism Diagnostic Observation
      Schedule-Generic. CONCLUSIONS: These findings support previous research
      demonstrating alterations in the prefrontal cortex, corpus callosum, and
      posterior vermis in children with autism and further suggest that alterations are
      associated with the severity of the autism phenotype. Continued research
      involving twins who are concordant and discordant for autism is essential to
      disentangle the genetic and environmental contributions to autism.

PMID- 19605540
TI  - Correlates of increased lean muscle mass in women with polycystic ovary syndrome.
AB  - OBJECTIVE: Muscle mass plays an important role in determining cardiovascular and
      metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean
      mass influences carotid intima-media thickness (IMT) in PCOS has not been
      assessed. DESIGN: Prospective investigation. METHODS: Ninety-five women with PCOS
      were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray
      absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum
      testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT
      were determined. Free androgen index (FAI) and insulin resistance (by QUICKI)
      were calculated. RESULTS: In PCOS, waist circumference and insulin were higher
      and QUICKI lower than in controls (P<0.01). Trunk fat mass, % trunk fat, and lean
      mass were higher in PCOS compared to controls (P<0.01), while total bone mass and
      BMD were similar. IMT was increased in PCOS (P<0.01) but only 15% of PCOS
      patients had abnormal (> or = 0.9 mm) values. Lean mass correlated with fat
      parameters, insulin, QUICKI, and FAI, but not with total testosterone; and after
      adjustments for insulin and QUICKI, lean mass still correlated with fat mass
      (P<0.01) but not FAI. Lean mass correlated with IMT (P<0.01), but this was
      dependent on insulin. However, excluding those patients with abnormal IMT values,
      IMT correlated with lean mass independently of insulin. Bone mass correlated with
      lean and fat mass, but not with insulin or androgen. PCOS patients with
      'pathological' IMT values had higher % trunk fat, lean mass, and insulin, lower
      QUICKI, and higher testosterone and FAI compared with those with normal IMT.
      CONCLUSION: Lean mass is increased in PCOS, while bone mass is similar to that of
      matched controls. The major correlates of lean mass are fat mass and insulin but
      not androgen. Lean mass also correlated with IMT, and although influenced by
      insulin, small changes in IMT may partially reflect changes in muscle mass, while
      clearly abnormal values relate to more severe abnormalities of PCOS.

PMID- 19605539
TI  - Relationship between cingulo-insular functional connectivity and autistic traits
      in neurotypical adults.
AB  - OBJECTIVE: The Social Responsiveness Scale-Adult Version (SRS-A) measures
      autistic traits that are continuously distributed in the general population.
      Based on increased recognition of the dimensional nature of autistic traits, the
      authors examined the neural correlates of these traits in neurotypical
      individuals using the SRS-A and established a novel approach to assessing the
      neural basis of autistic characteristics, attempting to directly relate SRS-A
      scores to patterns of functional connectivity observed in the pregenual anterior
      cingulate cortex, a region commonly implicated in social cognition. METHOD:
      Resting state functional magnetic resonance imaging scans were collected for 25
      neurotypical adults. All participants provided SRS-A ratings completed by an
      informant who had observed them in natural social settings. Whole brain-corrected
      connectivity analyses were then conducted using SRS-A scores as a covariate of
      interest. RESULTS: Across participants, a significant negative relationship
      between SRS-A scores and the functional connectivity of the pregenual anterior
      cingulate cortex with the anterior portion of the mid-insula was found.
      Specifically, low levels of autistic traits were observed when a substantial
      portion of the anterior mid-insula showed positive connectivity with the
      pregenual anterior cingulate cortex. In contrast, elevated levels of autistic
      traits were associated with negative connectivity between these two regions.
      CONCLUSIONS: Resting state functional connectivity of the pregenual anterior
      cingulate cortex-insula social network was related to autistic traits in
      neurotypical adults. Application of this approach in samples with autism spectrum
      disorders is needed to confirm whether this circuit is dimensionally related to
      the severity of autistic traits in clinical populations.

PMID- 19605541
TI  - Adrenal venous sampling in primary aldosteronism: a low dilution of adrenal
      venous blood is crucial for a correct interpretation of the results.
AB  - OBJECTIVE: In primary aldosteronism, adrenal venous sampling (AVS) is essential
      for subtype differentiation as it evaluates aldosterone secretion from both
      adrenals. Selectivity of adrenal sampling is assessed by the ratio of cortisol
      concentrations in adrenal venous blood and inferior vena cava blood
      (C(adrenal)/C(ivc)). Since the criteria for selective adrenal sampling differ
      among the reported literature, we performed a study to evaluate the influence of
      different selectivity criteria on AVS results. DESIGN AND METHODS: Reports of AVS
      were screened retrospectively. All AVS were performed with cosyntrophin infusion.
      Reports containing samples with C(adrenal)/C(ivc)>or=10 taken from both adrenals
      and at least one other adrenal sample characterised by C(adrenal)/C(ivc)>or=1.1
      were enrolled. For each individual, we chose reference samples that were defined
      by the highest C(adrenal)/C(ivc) achieved from each adrenal. The significance of
      the remaining samples with C(adrenal)/C(ivc)>or=1.1 was analysed in regard to
      their respective reference samples. We assessed the impact of analysed samples on
      identification of lateralisation of aldosterone secretion that is crucial for
      decisions concerning adrenalectomy. RESULTS: AVS reports of 87 patients were
      enrolled. A total of 225 adrenal samples were analysed and divided into five
      groups according to C(adrenal)/C(ivc):1.1-1.99, 2-2.99, 3-4.99, 5-9.99 and
      >or=10. By comparing reference with analysed samples, a concordant assessment
      with respect to lateralisation of aldosterone secretion was observed in 39, 52,
      72, 85 and 94% of the respective groups of analysed samples. CONCLUSION: AVS
      provides consistent information when adrenal samples with high cortisol
      concentrations are used.

PMID- 19605542
TI  - Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas:
      report of three cases.
AB  - OBJECTIVE: We aimed to gain insight into the functional consequences of ghrelin
      overproduction in patients with neuroendocrine tumors and its relations with
      disease characteristics and evolution. DESIGN: We retrospectively analyzed three
      cases of neuroendocrine carcinomas associated with very high levels of
      circulating ghrelin. METHODS: Between February and October 2007, serum ghrelin
      levels were determined in all patients with well-differentiated endocrine
      carcinoma referred to our center (n=72). Three patients were found to have
      circulating ghrelin levels >10-fold the upper limit of normal. The clinical,
      biochemical, and pathological characteristics of these three patients were
      reviewed. The ratio between circulating acyl and total ghrelin was determined,
      and tumor tissue expression of ghrelin was assayed by immunohistochemistry.
      RESULTS: The three patients had massive hyperghrelinemia (respectively 49 028, 63
      711, and 101 996 pg/ml), with <10% of acyl ghrelin. The corresponding primary
      tumors were located in the pancreas, rectum, and gallbladder; all were
      metastatic. There was no acromegaly; there was a decrease in appetite; and body
      mass index was low. Serum GH levels were only slightly increased and serum IGF1
      levels were normal. Immunoreactive ghrelin was detected in the tumor tissue in
      the two cases in which tissue material was available. All three patients died
      before 12 months after the diagnosis of hyperghrelinemia. CONCLUSION: Well
      differentiated neuroendocrine carcinomas of various origins may produce markedly
      high levels of circulating ghrelin, without evidence of clinical or functional
      consequences.

PMID- 19605543
TI  - The d3/fl-GH receptor gene polymorphism does not influence quality of life and
      body composition in GH-deficient adults receiving GH replacement therapy.
AB  - CONTEXT: The growth response to recombinant human growth hormone (rhGH) in GH
      deficient (GHD) patients may be influenced by polymorphisms in the growth hormone
      receptor (GHR) gene. OBJECTIVES: To investigate adults with GHD who have been
      treated with rhGH for more than 1 year to determine the relationship between
      genomic deletion of exon 3 in the GHR gene and quality of life (QoL), body
      composition (BC) and serum IGF1 levels, and to compare these variables to a
      healthy adult control population. DESIGN: Cross-sectional study. METHODS: A total
      of 100 healthy adult controls and 131 patients were studied. Deletion of exon 3
      in the GHR gene was determined in DNA that was isolated from peripheral blood.
      QoL was determined using the adult GHD assessment scale and three other validated
      QoL instruments. RESULTS: In the control population, the frequency of the
      genotypes was 53% fl/fl, 40% d3/fl and 7% d3/d3, and in the patient population,
      55, 39 and 6% respectively. There was no significant difference in QoL scores and
      BC in control subjects with the fl/fl genotype compared with those with the d3/d3
      or fl/d3 genotype. There was no difference in the rhGH dose required to optimize
      serum IGF1, QoL or BC in patients with the fl/fl genotype compared with those
      with the d3/d3 or d3/fl genotype. CONCLUSION: Deletion of exon 3 in the GHR gene
      does not influence adult height, QoL or BC of the normal adult population nor
      does it influence rhGH dose, QoL and BC in GHD adults treated with rhGH for more
      than 1 year.

PMID- 19605544
TI  - Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction
      in rats induced by fructose intake: renal organic ion transporter involvement.
AB  - Fructose consumption has been recently related to an epidemic of metabolic
      syndrome, and hyperuricemia plays a pathogenic role in fructose-induced metabolic
      syndrome. Fructose-fed rats showed hyperuricemia and renal dysfunction with
      reductions of the urinary uric acid/creatinine ratio and fractional excretion of
      uric acid (FE(ur)), as well as other features of metabolic syndrome. Lowering
      serum uric acid levels with allopurinol, rutin, and quercetin increased the
      urinary uric acid/creatinine ratio and FE(ur) and attenuated other fructose
      induced metabolic abnormalities in rats, demonstrating that hyperuricemia
      contributed to the deficiency of renal uric acid excretion in this model.
      Furthermore, we found that fructose upregulated the expression levels of
      rSLC2A9v2 and renal-specific transporter (rRST), downregulated the expression
      levels of organic anion transporters (rOAT1 and rUAT) and organic cation
      transporters (rOCT1 and rOCT2), with the regulators prostaglandin E(2) (PGE(2))
      elevation and nitric oxide (NO) reduction in rat kidney. Allopurinol, rutin, and
      quercetin reversed dysregulations of these transporters with PGE(2) reduction and
      NO elevation in the kidney of fructose-fed rats. These results suggested that
      dysregulations of renal rSLC2A9v2, rRST, rOAT1, rUAT, rOCT1, and rOCT2
      contributed to fructose-induced hyperuricemia and renal dysfunction. Therefore,
      these renal transporters may represent novel therapeutic targets for the
      treatment of hyperuricemia and renal dysfunction in fructose-induced metabolic
      syndrome.

PMID- 19605545
TI  - Role of pendrin in iodide balance: going with the flow.
AB  - Pendrin is expressed in the apical regions of type B and non-A, non-B
      intercalated cells, where it mediates Cl(-) absorption and HCO3(-) secretion
      through apical Cl(-)/HCO3(-) exchange. Since pendrin is a robust I(-)
      transporter, we asked whether pendrin is upregulated with dietary I(-)
      restriction and whether it modulates I(-) balance. Thus I(-) balance was
      determined in pendrin null and in wild-type mice. Pendrin abundance was evaluated
      with immunoblots, immunohistochemistry, and immunogold cytochemistry with
      morphometric analysis. While pendrin abundance was unchanged when dietary I(-)
      intake was varied over the physiological range, I(-) balance differed in pendrin
      null and in wild-type mice. Serum I(-) was lower, while I(-) excretion was higher
      in pendrin null relative to wild-type mice, consistent with a role of pendrin in
      renal I(-) absorption. Increased H2O intake enhanced differences between wild
      type and pendrin null mice in I(-) balance, suggesting that H2O intake modulates
      pendrin abundance. Raising water intake from approximately 4 to approximately 11
      ml/day increased the ratio of B cell apical plasma membrane to cytoplasm pendrin
      label by 75%, although circulating renin, aldosterone, and serum osmolality were
      unchanged. Further studies asked whether H2O intake modulates pendrin through the
      action of AVP. We observed that H2O intake modulated pendrin abundance even when
      circulating vasopressin levels were clamped. We conclude that H2O intake
      modulates pendrin abundance, although not likely through a direct, type 2
      vasopressin receptor-dependent mechanism. As water intake rises, pendrin becomes
      increasingly critical in the maintenance of Cl(-) and I(-) balance.

PMID- 19605546
TI  - Impaired transcription factor interplay in addition to advanced glycation end
      products suppress podocalyxin expression in high glucose-treated human podocytes.
AB  - Podocalyxin represents a Wilms' tumor suppressor protein (WT1)-regulated
      differentiation marker for glomerular epithelium. We provide evidence concerning
      mechanisms involved in the regulation of podocalyxin expression following long
      term exposure to increased (25 mM) glucose levels. Prolonged culture of
      conditionally immortalized human podocytes in 25 mM glucose induced suppression
      of podocalyxin expression both at the protein and mRNA levels, whereas WT1
      protein levels remained unaltered. WT1 interacted with another transcription
      factor, CRE-binding protein (CBP). This association was decreased by 40% in the
      presence of 25 mM glucose. Chromatin immunoprecipitation assays on chromatin from
      podocytes cultured in 25 mM glucose revealed reduced WT1 binding to podocalyxin
      promoter sequences, probably resulting from impaired WT1-CBP interactions. We
      explored the possible role of glucose-induced adducts (advanced glycation end
      products; AGEs) in impairing interactions between WT1 and CBP, with the use of
      aminoguanindine, an inhibitor of AGE formation. Podocytes were cultured in the
      simultaneous presence of 20 mM aminoguanidine and 25 mM glucose, and podocalyxin
      protein levels were examined. Aminoguanidine effectively prevented downregulation
      of podocalyxin protein levels but could not restore podocalyxin levels once
      expression was suppressed. Thus increased glucose apparently impaired the ability
      of WT1 to initiate transcription in part by decreased association of WT1 with
      CBP. Administration of aminoguanidine concomitant with increasing glucose levels
      in our in vitro model system protected from glucose-induced "silencing" of the
      podocalyxin gene, suggesting that AGEs play an important role in suppressing its
      expression in diabetic conditions.

PMID- 19605547
TI  - EGFR-PLCgamma1 signaling mediates high glucose-induced PKCbeta1-Akt activation
      and collagen I upregulation in mesangial cells.
AB  - Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We have
      recently shown that epidermal growth factor receptor (EGFR) transactivation
      mediates high glucose (HG)-induced collagen I upregulation through PI3K-PKCbeta1
      Akt signaling in mesangial cells (MC). Phospholipase Cgamma1 (PLCgamma1)
      interacts with activated growth factor receptors and activates classic PKC
      isoforms. We thus studied its role in HG-induced collagen I upregulation in MC.
      Primary rat MC were treated with HG (30 mM) or mannitol as osmotic control.
      Protein kinase activation was assessed by Western blotting and collagen I
      upregulation by Northern blotting. Diabetes was induced in rats by
      streptozotocin. HG treatment for 1 h led to PLCgamma1 membrane translocation and
      Y783 phosphorylation, both indicative of its activation. Mannitol was without
      effect. PLCgamma1 Y783 phosphorylation was also seen in cortex and glomeruli of
      diabetic rats. HG induced a physical association between EGFR and PLCgamma1 as
      identified by coimmunoprecipitation. PLCgamma1 activation required EGFR kinase
      activity since it was prevented by the EGFR inhibitor AG1478 or overexpression of
      kinase-inactive EGFR (K721A). Phosphoinositide-3-OH kinase inhibition also
      prevented PLCgamma1 activation. HG-induced Akt S473 phosphorylation, effected by
      PKCbeta1, was inhibited by the PLCgamma inhibitor U73122. PLCgamma1 inhibition or
      downregulation by small interference RNA also prevented HG-induced collagen I
      upregulation. Our results indicate that EGFR-PLCgamma1 signaling mediates HG
      induced PKCbeta1-Akt activation and subsequent collagen I upregulation in MC.
      Inhibition of EGFR or PLCgamma1 may provide attractive therapeutic targets for
      the treatment of diabetic nephropathy.

PMID- 19605548
TI  - The role of oxophytodienoate reductases in the detoxification of the explosive
      2,4,6-trinitrotoluene by Arabidopsis.
AB  - The explosive 2,4,6-trinitrotoluene (TNT) is a significant environmental
      pollutant that is both toxic and recalcitrant to degradation. Phytoremediation is
      being increasingly proposed as a viable alternative to conventional remediation
      technologies to clean up explosives-contaminated sites. Despite the potential of
      this technology, relatively little is known about the innate enzymology of TNT
      detoxification in plants. To further elucidate this, we used microarray analysis
      to identify Arabidopsis (Arabidopsis thaliana) genes up-regulated by exposure to
      TNT and found that the expression of oxophytodienoate reductases (OPRs) increased
      in response to TNT. The OPRs share similarity with the Old Yellow Enzyme family,
      bacterial members of which have been shown to transform explosives. The three
      predominantly expressed forms, OPR1, OPR2, and OPR3, were recombinantly expressed
      and affinity purified. Subsequent biochemical characterization revealed that all
      three OPRs are able to transform TNT to yield nitro-reduced TNT derivatives, with
      OPR1 additionally producing the aromatic ring-reduced products hydride and
      dihydride Meisenheimer complexes. Arabidopsis plants overexpressing OPR1 removed
      TNT more quickly from liquid culture, produced increased levels of transformation
      products, and maintained higher fresh weight biomasses than wild-type plants. In
      contrast, OPR1,2 RNA interference lines removed less TNT, produced fewer
      transformation products, and had lower biomasses. When grown on solid medium, two
      of the three OPR1 lines and all of the OPR2-overexpressing lines exhibited
      significantly enhanced tolerance to TNT. These data suggest that, in concert with
      other detoxification mechanisms, OPRs play a physiological role in xenobiotic
      detoxification.

PMID- 19605549
TI  - Physiological and transcriptome analysis of iron and phosphorus interaction in
      rice seedlings.
AB  - The antagonistic interaction between iron (Fe) and phosphorus (P) has been noted
      in the area of plant nutrition. To understand the physiology and molecular
      mechanisms of this interaction, we studied the growth performance, nutrient
      concentration, and gene expression profiles of root and shoot segments derived
      from 10-d-old rice (Oryza sativa) seedlings under four different nutrient
      conditions: (1) full strength of Fe and P (+Fe+P); (2) full strength of P and no
      Fe (-Fe+P); (3) full strength of Fe and no P (+Fe-P); and (4) without both Fe and
      P (-Fe-P). While removal of Fe in the growth medium resulted in very low shoot
      and root Fe concentrations, the chlorotic symptoms and retarded seedling growth
      were only observed on seedlings grown in the presence of P. Microarray data
      showed that in roots, 7,628 transcripts were significantly changed in abundance
      in the absence of Fe alone. Interestingly, many of these changes were reversed if
      P was also absent (-Fe-P), with only approximately 15% overlapping with -Fe alone
      (-Fe+P). Analysis of the soluble Fe concentration in rice seedling shoots showed
      that P deficiency resulted in significantly increased Fe availability within the
      plants. The soluble Fe concentration under -Fe-P conditions was similar to that
      under +Fe+P conditions. These results provide evidence that the presence of P can
      affect Fe availability and in turn can influence the regulation of Fe-responsive
      genes.

PMID- 19605550
TI  - RiceArrayNet: a database for correlating gene expression from transcriptome
      profiling, and its application to the analysis of coexpressed genes in rice.
AB  - Microarray data can be used to derive understanding of the relationships between
      the genes involved in various biological systems of an organism, given the
      availability of databases of gene expression measurements from the complete
      spectrum of experimental conditions and materials. However, there have been no
      reports, to date, of such a database being constructed for rice (Oryza sativa).
      Here, we describe the construction of such a database, called RiceArrayNet (RAN;
      http://www.ggbio.com/arraynet/), which provides information on coexpression
      between genes in terms of correlation coefficients (r values). The average number
      of coexpressed genes is 214, with sd of 440 at r >or= 0.5. Given the correlation
      between genes in a gene pair, the degrees of closeness between genes can be
      visualized in a relational tree and a relational network. The distribution of
      correlated genes according to degree of stringency shows how each gene is related
      to other genes. As an application of RAN, the 16-member L7Ae ribosomal protein
      family was explored for coexpressed genes and gene expression values within and
      between rice and Arabidopsis (Arabidopsis thaliana), and common and unique
      features in coexpression partners and expression patterns were observed for these
      family members. We observed a correlation pattern between Os01g0968800, a drought
      responsive element-binding transcription factor, Os02g0790500, a trehalose-6
      phosphate synthase, and Os06g0219500, a small heat shock factor, reflecting the
      fact that genes responding to the same biological stresses are regulated
      together. The RAN database can be used as a tool to gain insight into a
      particular gene by examining its coexpression partners.

PMID- 19605551
TI  - Polyphenoloxidase silencing affects latex coagulation in Taraxacum species.
AB  - Latex is the milky sap that is found in many different plants. It is produced by
      specialized cells known as laticifers and can comprise a mixture of proteins,
      carbohydrates, oils, secondary metabolites, and rubber that may help to prevent
      herbivory and protect wound sites against infection. The wound-induced browning
      of latex suggests that it contains one or more phenol-oxidizing enzymes. Here, we
      present a comprehensive analysis of the major latex proteins from two dandelion
      species, Taraxacum officinale and Taraxacum kok-saghyz, and enzymatic studies
      showing that polyphenoloxidase (PPO) is responsible for latex browning.
      Electrophoretic analysis and amino-terminal sequencing of the most abundant
      proteins in the aqueous latex fraction revealed the presence of three PPO-related
      proteins generated by the proteolytic cleavage of a single precursor (pre-PPO).
      The laticifer-specific pre-PPO protein contains a transit peptide that can target
      reporter proteins into chloroplasts when constitutively expressed in dandelion
      protoplasts, perhaps indicating the presence of structures similar to plastids in
      laticifers, which lack genuine chloroplasts. Silencing the PPO gene by
      constitutive RNA interference in transgenic plants reduced PPO activity compared
      with wild-type controls, allowing T. kok-saghyz RNA interference lines to expel
      four to five times more latex than controls. Latex fluidity analysis in silenced
      plants showed a strong correlation between residual PPO activity and the
      coagulation rate, indicating that laticifer-specific PPO plays a major role in
      latex coagulation and wound sealing in dandelions. In contrast, very little PPO
      activity is found in the latex of the rubber tree Hevea brasiliensis, suggesting
      functional divergence of latex proteins during plant evolution.

PMID- 19605553
TI  - KIOM-79, an Inhibitor of AGEs-Protein Cross-linking, Prevents Progression of
      Nephropathy in Zucker Diabetic Fatty Rats.
AB  - Advanced glycation end products (AGEs) have been implicated in the development of
      diabetic complications, including diabetic nephropathy. KIOM-79, an 80% ethanolic
      extract obtained from parched Puerariae Radix, gingered Magnolia Cortex,
      Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the
      development of renal disease in Zucker diabetic fatty rats, an animal model of
      type 2 diabetes. In vitro inhibitory effect of KIOM-79 on AGEs cross-linking was
      examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50 mg/kg/day) was
      given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood
      glucose, glycated hemoglobin, urinary albumin and creatinine excretions were
      monitored. Kidney histopathology, collagen accumulation, fibrinogen and
      transforming growth factor-beta 1 (TGF-beta1) expression were also examined. KIOM
      79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria
      in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular
      degeneration, collagen deposition and podocyte apoptosis. In the renal cortex,
      TGF-beta1, fibronectin mRNA and protein were significantly reduced by KIOM-79
      treatment. KIOM-79 reduces AGEs accumulation in vivo, AGE-protein cross-linking
      and protein oxidation. KIOM-79 could be beneficial in preventing the progression
      of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs
      deposition in the glomeruli.

PMID- 19605554
TI  - Seasonality Role on the Phenolics from Cultivated Baccharis dracunculifolia.
AB  - Baccharis dracunculifolia is the source of Brazilian green propolis (BGP).
      Considering the broad spectrum of biological activities attributed to green
      proplis, B. dracunculifolia has a great potential for the development of new
      cosmetic and pharmaceutical products. In this work, the cultivation of 10
      different populations of native B. dracunculifolia had been undertaken aiming to
      determine the role of seasonality on its phenolic compounds. For this purpose,
      fruits of this plant were collected from populations of 10 different regions, and
      100 individuals of each population were cultivated in an experimental area of
      1800 m(2). With respect to cultivation, the yields of dry plant, essential oil
      and crude extract were measured monthly resulting in mean values of 399 +/- 80 g,
      0.6 +/- 0.1% and 20 +/- 4%, respectively. The HPLC analysis allowed detecting
      seven phenolic compounds: caffeic acid, ferulic acid, aromadendrin-4'-methyl
      ether (AME), isosakuranetin, artepillin C, baccharin and 2-dimethyl-6
      carboxyethenyl-2H-1-benzopyran acid, which were the major ones throughout the 1
      year monthly analysis. Caffeic acid was detected in all cultivated populations
      with mean of 4.0%. AME displayed the wide variation in relation to other
      compounds showing means values of 0.65 +/- 0.13% at last quarter. Isosakuranetin
      and artepillin C showed increasing concentrations with values between 0% and 1.4%
      and 0% and 1.09%, respectively. The obtained results allow suggesting that the
      best time for harvesting this plant, in order to obtain good qualitative and
      quantitative results for these phenolic compounds, is between December and April.

PMID- 19605555
TI  - Pericentromeric sister chromatid cohesion promotes kinetochore biorientation.
AB  - Accurate chromosome segregation depends on sister kinetochores making bioriented
      attachments to microtubules from opposite poles. An essential regulator of
      biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper
      microtubule-kinetochore attachments. To identify additional biorientation
      pathways, we performed a systematic genetic analysis between the ipl1-321 allele
      and all nonessential budding yeast genes. One of the mutants, mcm21Delta,
      precociously separates pericentromeres and this is associated with a defect in
      the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly,
      Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this
      appears to be related to its role in pericentromeric cohesion. When
      pericentromeres are artificially tethered, Mcm21 is no longer needed for
      biorientation despite decreased Ipl1 activity. Taken together, these data reveal
      a specific role for pericentromeric linkage in ensuring kinetochore
      biorientation.

PMID- 19605556
TI  - ZO-1 stabilizes the tight junction solute barrier through coupling to the
      perijunctional cytoskeleton.
AB  - ZO-1 binds numerous transmembrane and cytoplasmic proteins and is required for
      assembly of both adherens and tight junctions, but its role in defining barrier
      properties of an established tight junction is unknown. We depleted ZO-1 in MDCK
      cells using siRNA methods and observed specific defects in the barrier for large
      solutes, even though flux through the small claudin pores was unaffected. This
      permeability increase was accompanied by morphological alterations and
      reorganization of apical actin and myosin. The permeability defect, and to a
      lesser extent morphological changes, could be rescued by reexpression of either
      full-length ZO-1 or an N-terminal construct containing the PDZ, SH3, and GUK
      domains. ZO-2 knockdown did not replicate either the permeability or
      morphological phenotypes seen in the ZO-1 knockdown, suggesting that ZO-1 and -2
      are not functionally redundant for these functions. Wild-type and knockdown MDCK
      cells had differing physiological and morphological responses to pharmacologic
      interventions targeting myosin activity. Use of the ROCK inhibitor Y27632 or
      myosin inhibitor blebbistatin increased TER in wild-type cells, whereas ZO-1
      knockdown monolayers were either unaffected or changed in the opposite direction;
      paracellular flux and myosin localization were also differentially affected.
      These studies are the first direct evidence that ZO-1 limits solute permeability
      in established tight junctions, perhaps by forming a stabilizing link between the
      barrier and perijunctional actomyosin.

PMID- 19605557
TI  - Glucosidase II beta subunit modulates N-glycan trimming in fission yeasts and
      mammals.
AB  - Glucosidase II (GII) plays a key role in glycoprotein biogenesis in the
      endoplasmic reticulum (ER). It is responsible for the sequential removal of the
      two innermost glucose residues from the glycan (Glc(3)Man(9)GlcNAc(2))
      transferred to Asn residues in proteins. GII participates in the
      calnexin/calreticulin cycle; it removes the single glucose unit added to folding
      intermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein
      glucosyltransferase. GII is a heterodimer whose alpha subunit (GIIalpha) bears
      the glycosyl hydrolase active site, whereas its beta subunit (GIIbeta) role is
      controversial and has been reported to be involved in GIIalpha ER retention and
      folding. Here, we report that in the absence of GIIbeta, the catalytic subunit
      GIIalpha of the fission yeast Schizosaccharomyces pombe (an organism displaying a
      glycoprotein folding quality control mechanism similar to that occurring in
      mammalian cells) folds to an active conformation able to hydrolyze p-nitrophenyl
      alpha-d-glucopyranoside. However, the heterodimer is required to efficiently
      deglucosylate the physiological substrates Glc(2)Man(9)GlcNAc(2) (G2M9) and
      Glc(1)Man(9)GlcNAc(2) (G1M9). The interaction of the mannose 6-phosphate receptor
      homologous domain present in GIIbeta and mannoses in the B and/or C arms of the
      glycans mediates glycan hydrolysis enhancement. We present evidence that also in
      mammalian cells GIIbeta modulates G2M9 and G1M9 trimming.

PMID- 19605558
TI  - Basolateral internalization of GPI-anchored proteins occurs via a clathrin
      independent flotillin-dependent pathway in polarized hepatic cells.
AB  - In polarized hepatocytes, the predominant route for apical resident proteins to
      reach the apical bile canalicular membrane is transcytosis. Apical proteins are
      first sorted to the basolateral membrane from which they are internalized and
      transported to the opposite surface. We have noted previously that transmembrane
      proteins and GPI-anchored proteins reach the apical bile canaliculi at very
      different rates. Here, we investigated whether these differences may be explained
      by the use of distinct endocytic mechanisms. We show that endocytosis of both
      classes of proteins at the basolateral membrane of polarized hepatic cells is
      dynamin dependent. However, internalization of transmembrane proteins is clathrin
      mediated, whereas endocytosis of GPI-anchored proteins does not require clathrin.
      Further analysis of basolateral endocytosis of GPI-anchored proteins showed that
      caveolin, as well as the small GTPase cdc42 were dispensable. Alternatively,
      internalized GPI-anchored proteins colocalized with flotillin-2-positive
      vesicles, and down-expression of flotillin-2 inhibited endocytosis of GPI
      anchored proteins. These results show that basolateral endocytosis of GPI
      anchored proteins in hepatic cells occurs via a clathrin-independent flotillin
      dependent pathway. The use of distinct endocytic pathways may explain, at least
      in part, the different rates of transcytosis between transmembrane and GPI
      anchored proteins.

PMID- 19605552
TI  - Molecular and chromosomal evidence for allopolyploidy in soybean.
AB  - Recent studies have documented that the soybean (Glycine max) genome has
      undergone two rounds of large-scale genome and/or segmental duplication. To shed
      light on the timing and nature of these duplication events, we characterized and
      analyzed two subfamilies of high-copy centromeric satellite repeats, CentGm-1 and
      CentGm-2, using a combination of computational and molecular cytogenetic
      approaches. These two subfamilies of satellite repeats mark distinct subsets of
      soybean centromeres and, in at least one case, a pair of homologs, suggesting
      their origins from an allopolyploid event. The satellite monomers of each
      subfamily are arranged in large tandem arrays, and intermingled monomers of the
      two subfamilies were not detected by fluorescence in situ hybridization on
      extended DNA fibers nor at the sequence level. This indicates that there has been
      little recombination and homogenization of satellite DNA between these two sets
      of centromeres. These satellite repeats are also present in Glycine soja, the
      proposed wild progenitor of soybean, but could not be detected in any other
      relatives of soybean examined in this study, suggesting the rapid divergence of
      the centromeric satellite DNA within the Glycine genus. Together, these
      observations provide direct evidence, at molecular and chromosomal levels, in
      support of the hypothesis that the soybean genome has experienced a recent
      allopolyploidization event.

PMID- 19605559
TI  - Peroxisome size provides insights into the function of autophagy-related
      proteins.
AB  - Autophagy is a major pathway of intracellular degradation mediated by formation
      of autophagosomes. Recently, autophagy was implicated in the degradation of
      intracellular bacteria, whose size often exceeds the capacity of normal
      autophagosomes. However, the adaptations of the autophagic machinery for
      sequestration of large cargos were unknown. Here we developed a yeast model
      system to study the effect of cargo size on the requirement of autophagy-related
      (Atg) proteins. We controlled the size of peroxisomes before their turnover by
      pexophagy, the selective autophagy of peroxisomes, and found that peroxisome size
      determines the requirement of Atg11 and Atg26. Small peroxisomes can be degraded
      without these proteins. However, Atg26 becomes essential for degradation of
      medium peroxisomes. Additionally, the pexophagy-specific phagophore assembly
      site, organized by the dual interaction of Atg30 with functionally active Atg11
      and Atg17, becomes essential for degradation of large peroxisomes. In contrast,
      Atg28 is partially required for all autophagy-related pathways independent of
      cargo size, suggesting it is a component of the core autophagic machinery. As a
      rule, the larger the cargo, the more cargo-specific Atg proteins become essential
      for its sequestration.

PMID- 19605560
TI  - Identification of a distal GLUT4 trafficking event controlled by actin
      polymerization.
AB  - The insulin-stimulated trafficking of GLUT4 to the plasma membrane in muscle and
      fat tissue constitutes a central process in blood glucose homeostasis. The
      tethering, docking, and fusion of GLUT4 vesicles with the plasma membrane (PM)
      represent the most distal steps in this pathway and have been recently shown to
      be key targets of insulin action. However, it remains unclear how insulin
      influences these processes to promote the insertion of the glucose transporter
      into the PM. In this study we have identified a previously uncharacterized role
      for cortical actin in the distal trafficking of GLUT4. Using high-frequency total
      internal reflection fluorescence microscopy (TIRFM) imaging, we show that insulin
      increases actin polymerization near the PM and that disruption of this process
      inhibited GLUT4 exocytosis. Using TIRFM in combination with probes that could
      distinguish between vesicle transport and fusion, we found that defective actin
      remodeling was accompanied by normal insulin-regulated accumulation of GLUT4
      vesicles close to the PM, but the final exocytotic fusion step was impaired.
      These data clearly resolve multiple steps of the final stages of GLUT4
      trafficking, demonstrating a crucial role for actin in the final stage of this
      process.

PMID- 19605562
TI  - The insulin-like growth factor (IGF)-I E-peptides modulate cell entry of the
      mature IGF-I protein.
AB  - Insulin-like growth factor (IGF)-I is a critical protein for cell development and
      growth. Alternative splicing of the igf1 gene gives rise to multiple isoforms. In
      rodents, proIGF-IA and proIGF-IB have different carboxy-terminal extensions
      called the E-peptides (EA and EB) and upon further posttranslational processing,
      produce the identical mature IGF-I protein. Rodent EB has been reported to have
      mitogenic and motogenic effects independent of IGF-I. However, effects of EA or
      EB on mature IGF-I, or whether proIGF-IA and proIGF-IB have different properties,
      have not been addressed. To determine whether the presence of EA or EB affected
      the distribution and stability of mature IGF-I protein, transient transfections
      of cDNAs encoding murine IGF-IA, IGF-IB, and mature IGF-I were performed in C2C12
      cells, a skeletal muscle cell line. IGF-I secretion was measured by enzyme-linked
      immunosorbent assay of the media, and did not differ between expression of proIGF
      IA, proIGF-IB, or mature IGF-I expression. Next, epitope-tagged constructs were
      transfected to determine cellular distribution of IGF-I, EA, and EB in the cells
      throughout the culture. IGF-I was detected in significantly fewer nontransfected
      cells in cultures transfected with mature IGF-I compared with transfection of
      proIGF-IA or proIGF-IB. These results demonstrate that EA and EB are not required
      for IGF-I secretion but that they increase cell entry of IGF-I from the media.
      This study provides evidence that the EA and EB may modulate IGF-I in addition to
      having independent activity.

PMID- 19605561
TI  - The Ccr4-NOT deadenylase subunits CNOT7 and CNOT8 have overlapping roles and
      modulate cell proliferation.
AB  - Accurate gene expression requires the precise control of mRNA levels, which are
      determined by the relative rates of nuclear (pre-)mRNA synthesis and processing,
      and cytoplasmic mRNA turnover. A key step in mRNA degradation is the removal of
      the poly(A) tail, which involves several deadenylases including components of the
      Ccr4-Not complex. Here, we focused on the role of the human paralogues CNOT7
      (hCaf1/Caf1a) and CNOT8 (hPop2/Caf1b/Calif), which possess deadenylase activity
      mediated by DEDD nuclease domains. We show that efficient proliferation requires
      both subunits, although combined knockdown of CNOT7 and CNOT8 further reduces
      cell proliferation indicating partial redundancy between these proteins.
      Interestingly, the function of CNOT7 in cell proliferation partly depends on its
      catalytic activity. On the other hand, the interaction between CNOT7 and BTG2, a
      member of the antiproliferative BTG/Tob family involved in transcription and mRNA
      decay appears less important for proliferation of MCF7 cells, suggesting that
      CNOT7 does not function solely in conjunction with BTG2. Further analysis of gene
      expression profiles of CNOT7 and/or CNOT8 knockdown cells underscores the partial
      redundancy between these subunits and suggests that regulation of several genes,
      including repression of the antiproliferative genes MSMB and PMP22, by the Ccr4
      Not complex contributes to cell proliferation.

PMID- 19605564
TI  - Evidence for high bi-allelic expression of activating Ly49 receptors.
AB  - Stochastic expression is a hallmark of the Ly49 family that encode the main MHC
      class-I-recognizing receptors of mouse natural killer (NK) cells. This highly
      polygenic and polymorphic family includes both activating and inhibitory receptor
      genes and is one of genome's fastest evolving loci. The inhibitory Ly49 genes are
      expressed in a stochastic mono-allelic manner, possibly under the control of an
      upstream bi-directional early promoter and show mono-allelic DNA methylation
      patterns. To date, no studies have directly addressed the transcriptional
      regulation of the activating Ly49 receptors. Our study shows differences in DNA
      methylation pattern between activating and inhibitory genes in C57BL/6 and F1
      hybrid mouse strains. We also show a bias towards bi-allelic expression of the
      activating receptors based on allele-specific single-cell RT-PCR in F1 hybrid NK
      cells for Ly49d and Ly49H expression in Ly49h(+/-) mice. Furthermore, we have
      identified a region of high sequence identity with possible transcriptional
      regulatory capacity for the activating Ly49 genes. Our results also point to a
      likely difference between NK and T-cells in their ability to transcribe the
      activating Ly49 genes. These studies highlight the complex regulation of this
      rapidly evolving gene family of central importance in mouse NK cell function.

PMID- 19605565
TI  - Probing the relationship between Gram-negative and Gram-positive S1 proteins by
      sequence analysis.
AB  - Escherichia coli ribosomal protein S1 is required for the translation initiation
      of messenger RNAs, in particular when their Shine-Dalgarno sequence is
      degenerated. Closely related forms of the protein, composed of the same number of
      domains (six), are found in all Gram-negative bacteria. More distant proteins,
      generally formed of fewer domains, have been identified, by sequence
      similarities, in Gram-positive bacteria and are also termed 'S1 proteins'.
      However in the absence of functional information, it is generally difficult to
      ascertain their relationship with Gram-negative S1. In this article, we report
      the solution structure of the fourth and sixth domains of the E. coli protein S1
      and show that it is possible to characterize their beta-barrel by a consensus
      sequence that allows a precise identification of all domains in Gram-negative and
      Gram-positive S1 proteins. In addition, we show that it is possible to
      discriminate between five domain types corresponding to the domains 1, 2, 3, 4-5
      and 6 of E. coli S1 on the basis of their sequence. This enabled us to identify
      the nature of the domains present in Gram-positive proteins and, subsequently, to
      probe the filiations between all forms of S1.

PMID- 19605563
TI  - The rho-guanine nucleotide exchange factor domain of obscurin activates rhoA
      signaling in skeletal muscle.
AB  - Obscurin is a large ( approximately 800-kDa), modular protein of striated muscle
      that concentrates around the M-bands and Z-disks of each sarcomere, where it is
      well positioned to sense contractile activity. Obscurin contains several
      signaling domains, including a rho-guanine nucleotide exchange factor (rhoGEF)
      domain and tandem pleckstrin homology domain, consistent with a role in rho
      signaling in muscle. We investigated the ability of obscurin's rhoGEF domain to
      interact with and activate small GTPases. Using a combination of in vitro and in
      vivo approaches, we found that the rhoGEF domain of obscurin binds selectively to
      rhoA, and that rhoA colocalizes with obscurin at the M-band in skeletal muscle.
      Other small GTPases, including rac1 and cdc42, neither associate with the rhoGEF
      domain of obscurin nor concentrate at the level of the M-bands. Furthermore,
      overexpression of the rhoGEF domain of obscurin in adult skeletal muscle
      selectively increases rhoA expression and activity in this tissue. Overexpression
      of obscurin's rhoGEF domain and its effects on rhoA alter the expression of rho
      kinase and citron kinase, both of which can be activated by rhoA in other
      tissues. Injuries to rodent hindlimb muscles caused by large-strain lengthening
      contractions increases rhoA activity and displaces it from the M-bands to Z
      disks, similar to the effects of overexpression of obscurin's rhoGEF domain. Our
      results suggest that obscurin's rhoGEF domain signals at least in part by
      inducing rhoA expression and activation, and altering the expression of
      downstream kinases in vitro and in vivo.

PMID- 19605566
TI  - Novel variants at KCTD10, MVK, and MMAB genes interact with dietary carbohydrates
      to modulate HDL-cholesterol concentrations in the Genetics of Lipid Lowering
      Drugs and Diet Network Study.
AB  - BACKGROUND: Several genome-wide association studies have identified novel loci
      (KCTD10, MVK, and MMAB) that are associated with HDL-cholesterol concentrations.
      Of the environmental factors that determine HDL cholesterol, high-carbohydrate
      diets have been shown to be associated with low concentrations. OBJECTIVE: The
      objective was to evaluate the associations of 8 single nucleotide polymorphisms
      (SNPs) located within the KCTD10, MVK, and MMAB loci with lipids and their
      potential interactions with dietary carbohydrates. DESIGN: KCTD10, MVK, and MMAB
      SNPs were genotyped in 920 subjects (441 men and 479 women) who participated in
      the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Biochemical
      measurements were made by using standard procedures. Dietary intakes were
      estimated by using a validated questionnaire. RESULTS: For the SNPs KCTD10_i5642G
      ->C and MVK_S52NG-->A, homozygotes for the major alleles (G) had lower HDL
      cholesterol concentrations than did carriers of the minor alleles (P = 0.005 and
      P = 0.019, respectively). For the SNP 12inter_108466061A-->G, homozygotes for the
      minor allele (G) had higher total cholesterol and LDL-cholesterol concentrations
      than did AG subjects (P = 0.030 and P = 0.034, respectively). Conversely,
      homozygotes for the major allele (G) at MMAB_3U3527G-->C had higher LDL
      cholesterol concentrations than did carriers of the minor allele (P = 0.034).
      Significant gene-diet interactions for HDL cholesterol were found (P < 0.001
      0.038), in which GG subjects at SNPs KCTD10_i5642G-->C and MMAB_3U3527G-->C and C
      allele carriers at SNP KCTD10_V206VT-->C had lower concentrations only if they
      consumed diets with a high carbohydrate content (P < 0.001-0.011). CONCLUSION:
      These findings suggest that the KCTD10 (V206VT-->C and i5642G-->C) and
      MMAB_3U3527G-->C variants may contribute to the variation in HDL-cholesterol
      concentrations, particularly in subjects with high carbohydrate intakes.

PMID- 19605567
TI  - Prevalence of daily hyperglycemia in obese type 2 diabetic men compared with that
      in lean and obese normoglycemic men: effect of consumption of a sucrose
      containing beverage.
AB  - BACKGROUND: Hyperglycemia forms a direct and independent risk factor for the
      development of cardiovascular comorbidities in type 2 diabetes. Consumption of
      sucrose-sweetened soft drinks might further increase the prevalence of
      hyperglycemic episodes. OBJECTIVE: The objective was to assess glycemic control
      in type 2 diabetic subjects and healthy lean and obese control subjects under
      strict dietary standardization but otherwise free-living conditions, with and
      without the consumption of soft drinks. DESIGN: Obese type 2 diabetic men (n =
      11) and lean (n = 10) and obese (n = 10) normoglycemic male control subjects
      participated in a randomized crossover study. The subjects were provided with a
      standardized diet in 2 periods, during which they consumed 250 mL water with or
      without (control) sucrose (37.5 g) 2 h after breakfast and lunch. Blood glucose
      concentrations were assessed by continuous glucose monitoring. RESULTS: In the
      type 2 diabetic subjects, the mean 24-h glucose concentrations were significantly
      elevated (9.1 +/- 0.6 mmol/L), and hyperglycemia (glucose >10 mmol/L) was evident
      over 33 +/- 8% (8 +/- 2 h) of a 24-h period (P < 0.01). Hyperglycemia was rarely
      present in the normoglycemic lean and obese control subjects (5 +/- 2%/24 h for
      both). Consumption of 75 g sucrose, equivalent to 2 cans of a soft drink, did not
      further augment the prevalence of hyperglycemia throughout the day in any group.
      CONCLUSIONS: Type 2 diabetic subjects taking oral blood glucose-lowering
      medication experience hyperglycemia during most of the daytime. Moderate
      consumption of sucrose-sweetened beverages does not further increase the
      prevalence of hyperglycemia in type 2 diabetic subjects or in normoglycemic lean
      or obese men.

PMID- 19605568
TI  - The evidence-based Mediterranean diet reduces coronary heart disease risk, and
      plant-derived monounsaturated fats may reduce coronary heart disease risk.

PMID- 19605569
TI  - {beta}-Carotene from rice for human nutrition?

PMID- 19605571
TI  - Application of zinc-bis-(DL-hydrogensaspartate) does not reduce apoptotic cell
      death in myocardial infarction in the rat heart.
AB  - BACKGROUND: Early studies in different stress models have shown potential
      beneficial effects of exogenous zinc application with reduction in the rate of
      apoptotic cell death. This has not been shown in models of myocardial infarction.
      METHODS: Rats were exposed to either brief episodes of acute ischemia followed by
      reperfusion (phase 1) or chronic coronary occlusion (phase 2). Animals were
      either treated with zinc or vehicle. Groups 1 and 3 received zinc-bis-(DL
      hydrogenaspartate) 10 mg/kg body weight as a single 5-mL bolus administered
      intraperitoneally 24 hours prior to coronary occlusion, groups 2 and 4 received
      saline. The infarct sizes were determined by triphenyltetrazolium chloride
      staining and expressed at relative areas to areas of ischemia. Histological
      slices of the rat's myocardium at the border zones of the infarcts were stained
      with the TUNEL method to assess for apoptosis. Animals in groups 5, 7, and 9
      received zinc, given once before and then repeated every 4 days after coronary
      occlusion, whereas groups 6, 8, and 10 received saline. Animals were observed for
      observation periods of 13 (groups 9 and 10), 16 (groups 7 and 8), or 19 weeks
      (groups 5 and 6), respectively. Two-dimensional echocardiography was performed to
      measure ejection fraction (EF) at baseline and at the end of the observation
      periods. TUNEL staining was used to detect and quantify apoptosis rate in the
      border zones of infarcts after the hearts were excised. RESULTS: Infarct sizes
      were 49% + 22% in group 1 (zinc + 30 minutes ischemia + 30 minutes reperfusion);
      48% + 10% in group 2 (vehicle + 30 minutes ischemia + 30 minutes reperfusion);
      42% + 11% in group 3 (zinc + 60 minutes ischemia + 30 minutes reperfusion); and
      41% + 23% in group 4 (vehicle + 60 minutes ischemia + 60 minutes reperfusion). In
      group 1, 11% + 6% of cells were apoptotic compared to 12% + 4% in group 2, 16% +
      9% in group 3, and 17% + 7% in group 4 (P > .05). In phase 2, echocardiography
      revealed a significant reduction in EF in all groups after coronary occlusion.
      There were no significant differences in EF between the 5 groups at baseline and
      at follow-up. TUNEL staining did not reveal any significant apoptosis after 13 to
      19 weeks. CONCLUSION: Application of zinc failed to result in reduction of
      infarct size after temporary coronary occlusion followed by reperfusion and did
      not demonstrate any reduction in apoptotic cell death. In chronic coronary
      occlusion, zinc also did not improve EF compared to controls in the presented
      model in rats. The mechanisms involved in antiapoptotic effects seem to be more
      complex and might not be inducible by simple zinc injections.

PMID- 19605570
TI  - Early milk feeding influences taste acceptance and liking during infancy.
AB  - BACKGROUND: We identified a model system that exploits the inherent taste
      variation in early feedings to investigate food preference development.
      OBJECTIVE: The objective was to determine whether exposure to differing
      concentrations of taste compounds in milk and formulas modifies acceptance of
      exemplars of the 5 basic taste qualities in a familiar food matrix. Specifically,
      we examined the effects of consuming hydrolyzed casein formulas (HCFs), which
      have pronounced bitter, sour, and savory tastes compared with breast milk (BM)
      and bovine milk-based formulas (MFs), in which these taste qualities are weaker.
      DESIGN: Subgroups of BM-, MF- and HCF-fed infants, some of whom were fed table
      foods, were studied on 6 occasions to measure acceptance of sweet, salty, bitter,
      savory, sour, and plain cereals. RESULTS: In infants not yet eating table foods,
      the HCF group ate significantly more savory-, bitter-, and sour-tasting and plain
      cereals than did the BM or MF groups. HCF infants displayed fewer facial
      expressions of distaste while eating the bitter and savory cereals, and they and
      BM infants were more likely to smile while they were eating the savory cereal. In
      formula-fed infants eating table foods, preferences for the basic tastes
      reflected the types of foods they were being fed. In general, those infants who
      ate more food displayed fewer faces of distaste. CONCLUSIONS: The type of formula
      fed to infants has an effect on their response to taste compounds in cereal
      before solid food introduction. This model system of research investigation sheds
      light on sources of individual differences in taste and perhaps cultural food
      preferences.

PMID- 19605572
TI  - The effect of intracoronary nicorandil on coronary myocardial bridging.
AB  - Medical treatments of coronary myocardial bridging (CMB) generally include beta
      blockers and calcium channel blockers. Nitrates are avoided because symptoms may
      worsen. Nicorandil is a hybrid of a nitrate and a potassium channel opener.
      However, the effect of nicorandil on CMB is unknown. We analyzed nicorandil
      reactivity at the site with CMB in 51 patients. Maximal and minimal diameters of
      CMB were measured by quantitative angiography at baseline and at 60 seconds after
      intracoronary administration of 200 mg nicorandil. The maximal diameter during
      diastole increased from 2.15 + 0.42 mm to 2.34 + 0.44 mm after administration of
      nicorandil (P < .001), and the minimal diameter during systole increased from
      1.24 + 0.63 mm to 1.67 + 0.64 mm (P < .001). Thus, nicorandil reduced the
      percentage vessel narrowing from 44.0 + 26.1% to 30.3 + 21.2% (P < .001). In 22
      patients, we also evaluated the effect of nitroglycerin. The maximal diameter
      during diastole increased from 2.25 + 0.47 mm to 2.51 + 0.44 mm after
      administration of nitroglycerin (P < .019), and the minimal diameter during
      systole decreased from 1.28 + 0.64 mm to 1.14 + 0.60 mm (P = .276). Thus,
      nitroglycerin augmented the percentage vessel narrowing from 44.9% + 25.0% to
      56.0% + 23.5% (P = .023). These results indicate that intracoronary
      administration of nicorandil could dilate coronary arteries during diastole as
      well as systole in patients with CMB during coronary angiography.

PMID- 19605573
TI  - Direct sequencing of Legionella pneumophila from respiratory samples for sequence
      based typing analysis.
AB  - We have developed a procedure to test the efficiency and reliability of
      sequencing of Legionella pneumophila genes directly from respiratory samples and
      have compared the results with those derived from cultured isolates. We tried to
      obtain the nucleotide sequences of six protein-coding loci included in the
      sequence-based typing scheme for Legionella pneumophila and three intergenic
      regions from 132 samples corresponding to 106 patients positive for urine
      antigen. A seminested PCR approach was used to amplify and sequence these nine
      loci directly from respiratory samples. Nucleotide sequences were directly
      obtained for 23 Legionella isolates and also for 66 respiratory secretions from a
      total of 69 patients. The efficiency of sequencing from respiratory secretions
      was higher than that of sequencing after the isolation of the Legionella
      isolates. Moreover, the perfect match between the sequences obtained by both
      approaches when respiratory samples and cultured isolates from the same patient
      were available corroborates the suitability of the direct sequencing approach for
      the identification of Legionella species and molecular epidemiology studies with
      Legionella species.

PMID- 19605574
TI  - Quantification of hepatitis C virus (HCV) RNA in a multicenter study:
      implications for management of HCV genotype 1-infected patients.
AB  - Assessment of the viral load in hepatitis C virus (HCV) genotype 1-infected
      patients is critical before, during, and after antiviral therapy. In patients
      achieving a rapid virological response at week 4 of treatment, the viral load at
      the baseline is considered a predictive criterion of a sustained virological
      response 24 weeks after the discontinuation of treatment. A >or=2-log(10) drop in
      the viral load at week 12 of treatment (early virological response) triggers the
      continuation of therapy. We organized a multicenter study (MS) for diagnostic
      laboratories involved in the quantification of HCV RNA. Commercial assays,
      including two based on real-time reverse transcription-PCR (TaqMan system), and
      in-house methods, were used by the 61 participants. The overall reproducibility
      of the commercial quantitative nucleic acid amplification techniques (qNAT) was
      acceptable. As the intermethod variability among commercial qNAT for HCV RNA was
      still present, the manufacturers of these test kits should join efforts to
      harmonize the means of quantification of HCV RNA. This study also shows that
      caution should be exercised when the baseline viral load is evaluated and when
      the 2-log(10) reduction after 12 weeks of therapy is interpreted. Finally, this
      MS confirms the higher sensitivity of the commercial qNAT based on the TaqMan
      system, making them the elective assays for the monitoring of therapy.

PMID- 19605575
TI  - Cooccurrence of predominant Panton-Valentine leukocidin-positive sequence type
      (ST) 152 and multidrug-resistant ST 241 Staphylococcus aureus clones in Nigerian
      hospitals.
AB  - Ninety-six clinical isolates of Staphylococcus aureus from Nigeria were
      characterized phenotypically and genetically. Twelve multidrug-resistant
      methicillin (meticillin)-resistant S. aureus (MRSA) isolates carrying a new
      staphylococcal cassette chromosome mec element and a high proportion of Panton
      Valentine leukocidin (PVL)-positive methicillin-susceptible S. aureus (MSSA)
      isolates were observed. The cooccurrence of multidrug-resistant MRSA and PVL
      positive MSSA isolates entails the risk of emergence of a multidrug-resistant PVL
      positive MRSA clone.

PMID- 19605576
TI  - Airway infection with a novel Cupriavidus species in persons with cystic
      fibrosis.
AB  - We describe the recovery and identification of a bacterium that represents a new
      species of the genus Cupriavidus from cultures of respiratory tract specimens
      from two patients with cystic fibrosis (CF). The elucidation of the role of this
      species in CF lung disease will require an evaluation of a greater number of
      cases.

PMID- 19605577
TI  - Efficacy of bilateral bronchoalveolar lavage for diagnosis of ventilator
      associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is a common nosocomial infection causing
      significant morbidity and mortality. The goal of this study was to determine the
      efficacy of bilateral versus unilateral bronchoalveolar lavage (BAL) for the
      detection of the causative bacterial agents of VAP. We retrospectively studied
      the quantitative bacterial cultures of 399 BAL sample pairs collected from 287
      mechanically ventilated patients over a 5-year period at a U.S. tertiary-care
      teaching hospital. Trauma was the underlying illness in 69% of patients. No
      evidence of bacterial infection was found in 226 BAL pairs (56.6%). Among 173
      positive BAL sample pairs, significant bacterial counts were detected exclusively
      in 6.4% of left-lung and 12.1% of right-lung samples. In contrast, 81.5% of
      positive sample pairs had significant bacterial counts in both lungs. All
      bacteria recovered at significant concentrations from bilateral samples would
      have been detected in a unilateral right-lung sample in 89% of positive sample
      pairs. Unilateral sampling would have failed to recover one or more significant
      isolates in 11% of positive pairs had only the right lung been sampled and in
      16.7% had only the left lung been sampled. Our study shows that preferential
      sampling of the right lung improves the diagnostic efficacy of unilateral BAL for
      the detection of the etiologic agents of VAP. If bilateral sampling is performed,
      our results also indicate that pooling left- and right-lung samples for a single
      quantitative culture is comparable to processing samples individually.

PMID- 19605578
TI  - Real-time quantitative reverse transcription-PCR assays specifically detecting
      bluetongue virus serotypes 1, 6, and 8.
AB  - Bluetongue virus (BTV) is a major pathogen of ruminants. Especially serotypes 1,
      6, and 8 are of concern to veterinary authorities in central Europe. This article
      describes highly sensitive real-time reverse transcription-PCR assays directed to
      BTV genome segment 2 for specific detection of BTV-1, -6, or -8 in animal
      samples.

PMID- 19605579
TI  - Detection in 2009 of the swine origin influenza A (H1N1) virus by a subtyping
      microarray.

PMID- 19605580
TI  - Prevalence and management of invalid GeneXpert enterovirus results obtained with
      cerebrospinal fluid samples: a 2-year study.
AB  - A total of 525 cerebrospinal fluid (CSF) samples submitted during the 2007 and
      2008 enteroviral seasons were included in a study to determine the prevalence of
      and potential risk factors for invalid Cepheid GeneXpert enterovirus assay (GXEA)
      results, as well as possible solutions for the problem. The invalid GXEA results
      were reported for 43 (8.2%) specimens and correlated with increased visibility of
      red blood cells (P < 0.0001) but not with CSF xanthochromia and clotting. Invalid
      GXEA result rates were markedly diminished by 82.1% and 96.0% and test
      sensitivities were minimally decreased by 1.7% and 3.6% when these specimens were
      tested at a 1:5 dilution and after a freeze-thaw cycle, respectively.

PMID- 19605581
TI  - Assessment of flocked swabs for use in identification of streptococcal
      pharyngitis.
AB  - We compared the performance of flocked swabs to that of traditional swabs for
      culture of beta-hemolytic streptococci in children with pharyngitis. Sensitivity
      was higher for flocked swabs, but this did not reach statistical significance. We
      conclude that flocked swabs can be used in place of traditional swabs for
      diagnosis of streptococcal pharyngitis.

PMID- 19605582
TI  - Report of neonatal meningitis due to Salmonella enterica serotype Agona and
      review of breast milk-associated neonatal Salmonella infections.
AB  - We present the first documented case of Salmonella enterica serotype Agona
      meningitis in a 6-day-old baby. S. enterica serotype Agona was isolated
      concurrently from infant cerebrospinal fluid and parental fecal samples, and
      Salmonella was isolated from breast milk. The role of breast milk in transmission
      of Salmonella enterica is discussed.

PMID- 19605583
TI  - Evaluation of the Cavidi ExaVir Load assay (version 3) for plasma human
      immunodeficiency virus type 1 load monitoring.
AB  - We evaluated the new low-cost ExaVir Load (version 3) reverse transcriptase viral
      load assay against the Roche Cobas Amplicor assay. Results for samples tested
      using the reverse transcriptase assay correlated well with those obtained with
      the Roche assay (r = 0.85; n = 202). The version 3 reverse transcriptase assay
      shows improved sensitivity compared to the previous version.

PMID- 19605584
TI  - Characterization of Listeria monocytogenes isolates from human listeriosis cases
      in Italy.
AB  - The objective of this study was to characterize by serotyping, pulsed-field gel
      electrophoresis (PFGE), and PCR amplification of virulence genes and markers of
      epidemic clones I, II, and III (ECI, ECII, and ECIII) 54 human isolates from
      apparently sporadic cases of infection occurring in the Lombardy region and in
      the province of Florence, Tuscany, Italy, in the years 1996 to 2007. Listeria
      monocytogenes isolates were provided by the clinical microbiology laboratories of
      the Lombardy region and the "Careggi" Hospital of Florence, Tuscany, Italy.
      Serotyping, PFGE after digestion with the AscI and ApaI enzymes, and PCR
      amplification for the inlA, inlC, and inlJ genes and ECI, ECII, and ECIII markers
      were performed according to procedures described previously. Twenty-five (46.3%)
      L. monocytogenes isolates were assigned to serotype 1/2a, 23 (42.6%) to serotype
      4b, and 6 (11.1%) to serotype 1/2b. Thirty-one AscI pulsotypes were recognized
      among the 54 human isolates. Eleven molecular subtype clusters, of which eight
      included indistinguishable pulsotypes and three included closely related
      pulsotypes, were shared by two to seven isolates. Fifteen isolates exhibited
      unique AscI pulsotypes. Three groups of clustered isolates and two apparently
      sporadic isolates generated EC amplicons. All strains tested positive for the
      inlA, inlC, and inlJ genes. Based on the results of serotyping and molecular
      typing, there were 11 occasions when L. monocytogenes strains with the same
      subtype were isolated from more than one listeriosis case. A total of 39 out of
      54 isolates (72.2%) were attributed to molecular subtype clusters. The results of
      the study suggest that routine subtyping of L. monocytogenes strains from human
      listeriosis cases could allow more-timely detection of outbreaks possibly caused
      by food-borne isolates from a common source and could lead to control of ongoing
      food exposure, thus preventing the occurrence of more cases.

PMID- 19605585
TI  - Characterization of clinical Enterococcus faecalis small-colony variants.
AB  - In this report, we present a clinical case of chronic aortic valve endocarditis
      caused by Enterococcus faecalis small-colony variants (SCVs), with ensuing
      characterization of the SCV phenotype in comparison to the clonally related
      normal phenotype with respect to alterations in microscopic and ultrastructural
      morphology, growth behavior, and metabolic pathways. In contrast to the normal
      phenotype, light and electron microscopy of the Enterococcus SCVs demonstrated
      the presence of heterogeneous cells of different sizes with aberrant shapes.
      Furthermore, SCVs showed excessive production of an intercellular substance and
      alterations in cell division displayed by a thick, coarse cell wall and
      incomplete, branched, and multiple cross walls without obvious cell separation.
      In addition, empty "ghost" cells were visible. In growth experiments, SCVs
      displayed an extended lag phase with delayed entrance into the stationary phase.
      Interestingly, SCV cells growing under aerobic conditions did not attain the
      growth and viability of the normal phenotype or those of SCVs growing under
      microaerobic conditions, suggesting impaired growth behavior and enhanced
      vulnerability in the presence of oxygen. By metabolite analysis, SCVs failed to
      produce significant amounts of acetate or lactate under aerobic growth conditions
      but were able to produce lactate under microaerobic growth conditions,
      implicating the induction of a fermentative metabolism. In conclusion, the
      observed structural alterations and changes in the cellular growth and metabolic
      pathways facilitated the survival of Enterococcus SCVs under microaerobic
      conditions in vitro and thus presumably in vivo during endocarditis.

PMID- 19605586
TI  - Role of annexin A2 in cellular entry of rabbit vesivirus.
AB  - The mechanisms of calicivirus attachment and internalization are not well
      understood, mainly due to the lack of a reliable cell-culture system for most of
      its members. In this study, rabbit vesivirus (RaV) virions were shown to bind
      annexin A2 (ANXA2) in a membrane protein fraction from HEK293T cells, using a
      virus overlay protein-binding assay and matrix-assisted laser
      desorption/ionization time-of-flight analysis. A monoclonal anti-ANXA2 antibody
      and small interfering RNA-mediated knockdown of ANXA2 expression in HEK293T cells
      reduced virus infection significantly, further supporting the role of ANXA2 in
      RaV attachment and/or internalization.

PMID- 19605587
TI  - Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant
      hepatitis (Labrea black fever) in the western Brazilian Amazon region.
AB  - The genotypes of hepatitis B (HBV) and delta (HDV) viruses circulating among
      fulminant hepatitis cases from the western Amazon Basin of Brazil were
      characterized in this study. HBV and HDV isolates were obtained from liver
      samples from 14 patients who developed fulminant hepatitis and died during 1978
      1989. HBV DNA and HDV RNA were detected in all samples. Phylogenetic analyses of
      HDV sequences showed that they all clustered with previously characterized
      sequences of HDV genotype 3 (HDV-3). HBV genotypes F, A and D were found in 50.0,
      28.6 and 21.4 % of cases, respectively. These results confirm the predominance of
      HDV-3 in South America and its association with the severe form of hepatitis, and
      the finding of the co-infection of HDV-3 with different genotypes of HBV suggests
      that the association between HDV-3 and HBV-F is not necessarily causally related
      to a more severe clinical course of infection.

PMID- 19605588
TI  - Prion adsorption to stainless steel is promoted by nickel and molybdenum.
AB  - Prions are infectious agents resulting from the conversion of a normal cellular
      protein, PrP(C), to a misfolded species, PrP(Sc). Iatrogenic transmission of
      prions is known from surgical procedures involving stainless steel materials.
      Here, it was shown that stainless steel containing nickel and molybdenum binds
      PrP(Sc) more efficiently and transmits infection to cells in culture to a higher
      degree than if these elements are not present. Furthermore, both nickel and
      molybdenum alone adsorbed PrP(Sc), and nickel powder could be used to extract
      PrP(Sc) from dilute solutions, thus providing a simple approach to concentration
      of PrP(Sc). The fact that nickel and molybdenum in steel alloys increased the
      binding affinity, and bound infectivity, of PrP(Sc) is an important issue to
      consider in the manufacture of surgical instruments and abattoir tools.

PMID- 19605589
TI  - Genetic and functional characterization of human immunodeficiency virus type 1
      VprC variants from north India: presence of unique recombinants with mosaic
      genomes from B, C and D subtypes within the open reading frame of Vpr.
AB  - The human immunodeficiency virus type 1 (HIV-1) epidemic in India is
      predominantly caused by genetic subtype C, though other minor subtypes have also
      been reported. One of the major accessory proteins of HIV-1, namely Vpr, is known
      to influence key steps in viral replication, cell cycle progression, promoter
      activation, apoptosis and pathogenesis. Therefore, we carried out a genetic and
      functional analysis of the Vpr variants from eight HIV-1-infected individuals
      from north India. The sequence analyses revealed that six of eight samples
      clustered with ancestral subtype C. Remarkably, five of these showed a conserved
      and region-specific L64P mutation, located in the predicted third alpha-helix.
      This change adversely affected their ability to activate the HIV-1 long terminal
      repeat promoter without compromising their ability to cause apoptosis. Bootscan,
      phylogenetic and SimPlot analysis of the remaining two samples (VprS2 and A6)
      revealed very interesting mosaic genomes derived from B, C and D subtypes. The N
      terminal half of the VprS2 gene consisted of genomic segments derived from
      subtypes B/D, C and D but the C-terminal half was derived predominantly from
      subtype C. Interestingly the N-terminal half of sample A6 also showed similar
      B/D, C and D inter-subtype recombinant structure but the C-terminal half was
      entirely derived from the consensus B subtype. Multiple breakpoints in a short
      stretch of 291 nt encoding the Vpr gene strongly suggest that this region is a
      potential hot-spot for the formation of inter-subtype recombinants and also
      highlight the importance of the rapidly evolving HIV-1 epidemic in the north
      Indian region due to multiple genetic subtypes.

PMID- 19605590
TI  - Isolation and genomic characterization of the first Norway rat (Rattus
      norvegicus) papillomavirus and its phylogenetic position within Pipapillomavirus,
      primarily infecting rodents.
AB  - A series of papillomavirus (PV) types have been isolated from different rodent
      species, and most of them belong to the genus Pipapillomavirus. We isolated and
      sequenced the complete genome of a novel PV type (designated RnPV) from the oral
      cavity of the Norway rat (Rattus norvegicus), as well as an L1 gene fragment from
      hair-follicle cells of the European beaver (Castor fiber). As inferred from amino
      acid sequence data, RnPV clustered within the beta+gamma+pi+Xi-PV supertaxon as a
      member of the genus Pipapillomavirus. The closest relatives of RnPV were McPV-2
      and MmPV, and time estimates indicated that the genus Pipapillomavirus originated
      in the late Cenozoic era. The close relationship of RnPV to other murid PV types
      supports the hypothesis of co-divergence between members of the genus
      Pipapillomavirus and their hosts. However, the derived Neogene origin of the
      genus Pipapillomavirus is much younger than has been considered for the Rodentia
      as the primary hosts, indicating that alternative interpretations of the
      phylogenetic trees should be conceived.

PMID- 19605591
TI  - Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus
      4.
AB  - Many acute viral infections can be controlled by vaccination; however,
      vaccinating against persistent infections remains problematic. Herpesviruses are
      a classic example. Here, we discuss their immune control, particularly that of
      gamma-herpesviruses, relating the animal model provided by murid herpesvirus-4
      (MuHV-4) to human infections. The following points emerge: (i) CD8(+) T-cell
      evasion by herpesviruses confers a prominent role in host defence on CD4(+) T
      cells. CD4(+) T cells inhibit MuHV-4 lytic gene expression via gamma-interferon
      (IFN-gamma). By reducing the lytic secretion of immune evasion proteins, they may
      also help CD8(+) T cells to control virus-driven lymphoproliferation in mixed
      lytic/latent lesions. Similarly, CD4(+) T cells specific for Epstein-Barr virus
      lytic antigens could improve the impact of adoptively transferred, latent antigen
      specific CD8(+) T cells. (ii) In general, viral immune evasion necessitates
      multiple host effectors for optimal control. Thus, subunit vaccines, which tend
      to prime single effectors, have proved less successful than attenuated virus
      mutants, which prime multiple effectors. Latency-deficient mutants could make
      safe and effective gamma-herpesvirus vaccines. (iii) The antibody response to
      MuHV-4 infection helps to prevent disease but is suboptimal for neutralization.
      Vaccinating virus carriers with virion fusion complex components improves their
      neutralization titres. Reducing the infectivity of herpesvirus carriers in this
      way could be a useful adjunct to vaccinating naive individuals with attenuated
      mutants.

PMID- 19605592
TI  - Arthroscopic treatment of multidirectional shoulder instability in athletes: a
      retrospective analysis of 2- to 5-year clinical outcomes.
AB  - BACKGROUND: There are few reports in the literature detailing the arthroscopic
      treatment of multidirectional instability of the shoulder. HYPOTHESIS:
      Arthroscopic management of symptomatic multidirectional instability in an
      athletic population can successfully return athletes to sports with a high rate
      of success as determined by patient-reported outcome measures. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Forty patients (43 shoulders) with
      multidirectional instability of the shoulder were treated via arthroscopic means
      and were evaluated at a mean of 33.5 months postoperatively. The mean patient age
      was 19.1 years (range, 14-39). There were 24 male patients and 16 female
      patients. Patients were evaluated with the American Shoulder and Elbow Surgeons
      and Western Ontario Shoulder Instability scoring systems. Stability, strength,
      and range of motion were also evaluated with patient-reported scales. RESULTS:
      The mean American Shoulder and Elbow Surgeons score postoperatively was 91.4 of
      100 (range, 59.9-100). The mean Western Ontario Shoulder Instability
      postoperative percentage score was 91.1 of 100 (range, 72.9-100). Ninety-one
      percent of patients had full or satisfactory range of motion, 98% had normal or
      slightly decreased strength, and 86% were able to return to their sport with
      little or no limitation. CONCLUSION: Arthroscopic methods can provide an
      effective treatment for symptomatic multidirectional instability in an athletic
      population.

PMID- 19605593
TI  - Oral immunization with attenuated Salmonella enterica serovar Typhimurium
      encoding Cryptosporidium parvum Cp23 and Cp40 antigens induces a specific immune
      response in mice.
AB  - Attenuated Salmonella enterica serovar Typhimurium vaccine strain SL3261 was used
      as an antigen delivery system for the oral immunization of mice against two
      Cryptosporidium parvum antigens, Cp23 and Cp40. Each antigen was subcloned into
      the pTECH1 vector system, which allows them to be expressed as fusion proteins
      with highly immunogenic fragment C of tetanus toxin under the control of the
      anaerobically inducible nirB promoter. The recombinant vector was introduced into
      Salmonella Typhimurium vaccine strain SL3261, and the stable soluble expression
      of the chimeric protein was evaluated and confirmed by Western blotting with
      polyclonal C. parvum antisera. Mice were inoculated orally with a single dose of
      SL3261/pTECH-Cp23 or Cp40, respectively, and plasmid stability was demonstrated
      both in vitro and in vivo. Specific serum immunoglobulin G (IgG) antibodies
      against the Cp23 or Cp40 antigen were detected by enzyme-linked immunosorbent
      assay 35 days after immunization. Also, serum IgA and mucosal (feces) IgA
      antibodies were detected in 30% of the mice immunized with Cp23. In addition,
      prime-boosting with Cp23 and Cp40 DNA vaccine vectors followed by Salmonella
      immunization significantly increased antibody responses to both antigens. Our
      data show that a single oral inoculation with recombinant S. Typhimurium SL3261
      can induce specific antibody responses to the Cp23 or Cp40 antigen from C. parvum
      in mice, suggesting that recombinant Salmonella is a feasible delivery system for
      a vaccine against C. parvum infection.

PMID- 19605595
TI  - Development and validation of a fluorescent microsphere immunoassay for soluble
      CD30 testing.
AB  - Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a
      useful prognostic marker in solid organ transplantation, lymphoproliferative
      disorders, autoimmunity, and various parasitic diseases. In this study we report
      the development and validation of a fluorescent microsphere immunoassay for the
      detection of sCD30 in serum, plasma, and culture supernatants. The dynamic range
      of this assay is 1 to 400 ng/ml, and the rate of recovery of various
      concentrations of recombinant sCD30 ranges from 97 to 116% (average recovery,
      105%). The test showed a high degree of precision in both intra-assay and
      interassay studies (coefficients of variation, as high as 7% and 8%,
      respectively), with a sensitivity of 1 ng/ml. The normal reference range
      calculated for a cohort of 151 healthy individuals was 1 to 29 ng/ml. The
      clinical usefulness of the sCD30 fluorescent microsphere immunoassay was
      demonstrated by showing that levels of sCD30 have a positive correlation with
      specimens containing high titers of anti-double-stranded DNA antibodies and high
      titers of immunoglobulin G against Leishmania species. Given the multiplexing
      potential of the sCD30 fluorescent microsphere immunoassay reported in this
      study, it is expected that testing of sCD30 concentrations along with those of
      other cytokines will become an important diagnostic tool for selected
      immunological and inflammatory diseases where Th2-type cytokine responses have
      been reported.

PMID- 19605594
TI  - Towards identification of the mechanisms of action of parasite-derived peptide
      GK1 on the immunogenicity of an influenza vaccine.
AB  - Previous studies have shown that the synthetic peptide GK1, derived from Taenia
      crassiceps cysticerci, enhances the immunogenicity of the commercial inactivated
      influenza vaccine Fluzone in both young and aged mice. In particular, antibody
      responses were much improved. Since GK1 is a peptide and is rapidly cleared from
      the body, it offers the possibility to improve vaccine performance without
      undesirable effects. This study was therefore designed to understand the
      mechanisms of action involved in the adjuvant properties of GK1. For this,
      transgenic mice expressing a T-cell receptor specific for an epitope from the
      influenza virus hemagglutinin (HA) protein were employed. The GK1 peptide
      significantly increased the in vivo proliferative response of HA-specific CD4+ T
      cells when it was coimmunized with the HA epitope. Dendritic cells treated in
      vitro with GK1 were capable of enhancing T-cell activation. Furthermore, in
      synergy with lipopolysaccharide, GK1 enhanced the expression of major
      histocompatibility complex class II and costimulatory molecules of dendritic
      cells and promoted the secretion of proinflammatory cytokines and chemokines upon
      antigen-driven T-cell interaction. These data provide important insights into the
      mechanism that underlies the GK1 adjuvant capacity observed previously and
      underline the feasibility of using the transgenic mouse model described herein as
      a tool for investigation of the modes of action of different influenza vaccine
      adjuvants.

PMID- 19605596
TI  - Single-antigen serological testing for bovine tuberculosis.
AB  - Antibody responses are useful indicators of Mycobacterium bovis infection of
      cattle. Tests for such responses often use multiple M. bovis antigens as
      detection probes. This is recommended because responses to single antigens may be
      too variable for consistent diagnosis. However, the use of multiple antigens
      increases costs and the risk of false-positive results. As an alternative, the
      SeraLyte-Mbv system detects responses to a single M. bovis antigen, MPB83, by
      using a chemiluminescent testing platform with a high degree of analytical
      sensitivity. Testing with the SeraLyte-Mbv system was conducted in a blinded
      fashion with sera from experimentally infected and control cattle. To assess the
      species specificity of the single-antigen test, the sample included sera from
      animals infected with M. bovis (n = 27), M. kansasii (n = 4), M. avium subsp.
      paratuberculosis (n = 11), M. avium subsp. avium (n = 12), and uninfected animals
      (n = 15). Upon unblinding of the results, the sensitivity of the SeraLyte-Mbv
      system relative to the results for animals with known M. bovis infection was 89%.
      Consistent with the conservation of MPB83 sequences within the genus
      Mycobacterium, all 4 M. kansasii-infected animals tested positive with the
      SeraLyte-Mbv system and all 23 M. avium-infected animals tested negative. Blinded
      analysis of 30 serum samples collected from nine animals at various time points
      postinfection indicated 100% sensitivity after > or = 3 months postinfection. All
      15 uninfected samples in the blinded sample set tested negative with the SeraLyte
      Mbv system. Unblinded analysis of sera from an additional 895 animals in 10
      accredited bovine tuberculosis-free states revealed 98% specificity overall. The
      results support the feasibility of single-antigen testing for bovine tuberculosis
      with the SeraLyte-Mbv system.

PMID- 19605597
TI  - Comparative evaluation of the immune responses and protection engendered by
      LC16m8 and Dryvax smallpox vaccines in a mouse model.
AB  - The immune response elicited by LC16m8, a candidate smallpox vaccine that was
      developed in Japan by cold selection during serial passage of the Lister vaccine
      virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model.
      LC16m8 carries a mutation resulting in the truncation of the B5 protein, an
      important neutralizing target of the extracellular envelope form of vaccinia
      virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that
      neutralized both EV and the intracellular mature form of vaccinia virus and
      provoked cell-mediated immune responses, including the activation of CD4+ and
      CD8+ cells, similarly to Dryvax. Mice inoculated with LC16m8 had detectable but
      low levels of anti-B5 IgG compared to Dryvax, but both Dryvax and LC16m8 sera
      neutralized vaccinia virus EV in vitro. A truncated B5 protein (approximately 8
      kDa) was expressed abundantly in LC16m8-infected cells, and both murine immune
      sera and human vaccinia virus immunoglobulin recognized the truncated recombinant
      B5 protein in antigen-specific enzyme-linked immunosorbent assays. At a high-dose
      intranasal challenge (100 or 250 50% lethal doses), LC16m8 and Dryvax conferred
      similar levels of protection against vaccinia virus strain WR postvaccination.
      Taken together, the results extend our current understanding of the protective
      immune responses elicited by LC16m8 and indicate that the relative efficacy in a
      mouse model rivals that of previously licensed smallpox vaccines.

PMID- 19605598
TI  - Safety and immunogenicity of the Merck adenovirus serotype 5 (MRKAd5) and MRKAd6
      human immunodeficiency virus type 1 trigene vaccines alone and in combination in
      healthy adults.
AB  - Preexisting immunity to adenovirus serotype 5 (Ad5) diminishes immune responses
      to vaccines using Ad5 as a vector. Alternate Ad serotypes as vaccine vectors
      might overcome Ad5-specific neutralizing antibodies and enhance immune responses
      in populations with a high prevalence of Ad5 immunity. To test this hypothesis,
      healthy human immunodeficiency virus (HIV)-seronegative adults were enrolled in a
      blinded, randomized, dose-escalating, placebo-controlled study. In part A,
      subjects with baseline Ad6 titers of < or = 18 received the Merck Ad6 (MRKAd6)
      HIV type 1 (HIV-1) trigene vaccine at weeks 0, 4, and 26. In part B, subjects
      stratified by Ad5 titers (< or = 200 or >200) and Ad6 titers (< or = 18 or >18)
      received the MRKAd5-plus-MRKAd6 (MRKAd5+6) HIV-1 trigene vaccine at weeks 0, 4,
      and 26. Immunogenicity was assessed by an enzyme-linked immunospot (ELISPOT)
      assay at week 30. No serious adverse events occurred. MRKAd6 trigene vaccine
      recipients responded more often to Nef than to Gag or Pol. In part A, ELISPOT
      response rates to > or = 2 vaccine antigens were 14%, 63%, and 71% at 10(9),
      10(10), and 10(11) viral genomes (vg)/dose, respectively. All responders had
      positive Nef-specific ELISPOT results. In part B, Nef-ELISPOT response rates at
      10(10) vg/dose of the MRKAd5+6 trigene vaccine were 50% in the low-Ad5/low-Ad6
      stratum (n = 8), 78% in the low-Ad5/high-Ad6 stratum (n = 9), 75% in the high
      Ad5/low-Ad6 stratum (n = 8), and 44% in the high-Ad5/high-Ad6 stratum (n = 9).
      The MRKAd6 and MRKAd5+6 trigene vaccines elicited dose-dependent responses
      predominantly to Nef and were generally well tolerated, indicating that Ad6
      should be considered a candidate vector for future vaccines. Although small
      sample sizes limit the conclusions that can be drawn from this exploratory study,
      combining two Ad vectors may be a useful vaccine strategy for circumventing
      isolated immunity to a single Ad serotype.

PMID- 19605600
TI  - Clinical nutrition scores are superior for the prognosis of haemodialysis
      patients compared to lab markers and bioelectrical impedance.
AB  - BACKGROUND: Malnutrition is closely related to inflammation and atherosclerosis
      in uraemic patients. There is still debate on how to quantify nutritional status
      in order to achieve the best prediction of mortality and hospitalization.
      METHODS: Different methods to detect malnutrition were prospectively investigated
      for their prognostic impact on mortality and hospitalization of haemodialysis
      (HD) patients. We compared clinical nutrition scores (body mass index, BMI;
      subjective global assessment, SGA; malnutrition inflammation score, MIS; and
      nutritional risk screening, NRS) to lab parameters of protein and lipid
      metabolism, or bioelectrical impedance analysis (BIA) in 90 HD patients. Over a 3
      year follow-up, all-cause mortality and hospitalization were evaluated using a
      Cox regression model. RESULTS: The scores SGA, NRS, MIS, serum albumin,
      prealbumin, transferrin and BIA were predictive of both mortality and
      hospitalization. Elevated CRP predicted only a significantly higher mortality.
      After adjustment for age, gender, dialysis vintage and diabetes status, the best
      prognostic parameters for mortality were the clinical nutrition scores, MIS-Index
      > or = 10 [HR 6.25 (2.82-13.87), P < 0.001], NRS [HR 4.24 (1.92-9.38), P < 0.001]
      and SGA B/C [HR 2.70 (1.14-6.41), P < 0.05]. CONCLUSIONS: In HD patients, serum
      markers of protein metabolism and BIA can be used for evaluation of the
      nutritional status. However, with regard to mortality and hospitalization risk,
      the individual clinical nutrition scores are superior compared to lab markers and
      BIA. To confirm malnutrition, we propose using clinical nutrition score generally
      or at least in the case of two malnutrition-positive parameters (lab, BIA, BMI).

PMID- 19605601
TI  - The economic benefits of preventing end-stage renal disease in patients with type
      2 diabetes mellitus.

PMID- 19605602
TI  - New aspects of pre-eclampsia: lessons for the nephrologist.

PMID- 19605599
TI  - Antiretroviral therapy restores diversity in the T-cell receptor Vbeta repertoire
      of CD4 T-cell subpopulations among human immunodeficiency virus type 1-infected
      children and adolescents.
AB  - Human immunodeficiency virus (HIV) type 1 infection perturbs the T-cell receptor
      (TCR) Vbeta repertoire. The TCR CDR3 length diversity of individual Vbeta
      families was examined within CD45RA and CD45RO CD4 T cells to assess the impact
      of the virus on clonality throughout CD4 T-cell activation and differentiation. A
      cross-sectional and longitudinal cohort study of 13 HIV-infected and 8 age
      matched healthy children and adolescents examined the Vbeta CDR3 length profiles
      within CD4 T-cell subsets by the use of spectratyping. HIV-infected subjects
      demonstrated higher numbers of perturbations in CD4 CD45RA T cells (5.8 +/- 4.9
      Vbeta families) than healthy individuals (1.6 +/- 1.8 Vbeta families) (P = 0.04).
      Surprisingly, CD4 CD45RO central memory T cells from infected subjects showed no
      increased perturbations compared to the perturbations for the same cells from
      healthy subjects (2.9 +/- 3.1 and 1.1 +/- 1.8 Vbeta families, respectively; P =
      0.11). CD4 CD45RA TCR perturbations were higher among infected subjects with >25%
      CD4 cells than healthy subjects (mean number of perturbed Vbeta families, 6.6 +/-
      5.4; P = 0.04). No correlations between perturbations in CD4 subsets and
      pretherapy age or viral load were evident. In contrast to CD8 T cells, HIV
      induces TCR disruptions within CD45RA but not CD45RO CD4 T cells. Therapy-induced
      viral suppression resulted in increases in thymic output and the normalization of
      the diversity of TCR within CD45RA CD4 T cells after 2 months of treatment.
      Perturbations occur prior to CD4 T-cell attrition and normalize with effective
      antiretroviral therapy. The impact of HIV on the diversity of TCR within naive,
      central memory, and effector memory CD4 T cells is distinctly different from that
      in CD8 T cells.

PMID- 19605603
TI  - Impact of drugs approved for treating ADHD on the cell survival and energy
      metabolism: an in-vitro study in human neuronal and immune cells.
AB  - The oxidative and antioxidative properties of psychostimulants such as
      methylphenidate and amphetamine are discussed controversially. The aim of the
      present study was to evaluate the impact of psychostimulants and atomoxetine in
      different concentrations between 31.25 and 5000 ng/ml on the survival of human
      neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and the
      impact of psychostimulants and atomoxetine in different concentrations between
      500 and 5000 ng/ml on energy metabolism (adenosine triphosphate [ATP] content) in
      SH-SY5Y cells. Statistical analysis revealed that incubation for 24 h with
      amphetamine led to a significantly enhanced cell survival in both cell lines
      after treatment with various (32.5, 125, 250 and 1250 ng/ml) concentrations.
      Methylphenidate and atomoxetine induced a significantly enhanced cell survival at
      lower concentrations in the SH-SY5Y cell line, whereas in the U-937 cell line
      higher concentrations increased the cell survival. Incubation with the highest
      concentration of methylphenidate (5000 ng/ml) caused a significant reduction of
      cell survival in both cell types. Measurement of ATP contents in the neuronal
      cell line revealed no significant effects of the investigated compounds. Our
      results show that the examined substances exert concentration-dependent effects
      on cell survival in both applied cell lines.

PMID- 19605604
TI  - Nurses' attitudes towards end-of-life decisions in medical practice: a nationwide
      study in Flanders, Belgium.
AB  - We investigated on a nationwide level the attitudes of nurses towards end-of-life
      decisions (ELDs) that may hasten death and towards their role in those decisions.
      We took a representative random sample of 6000 nurses in Flanders, Belgium.
      Response rate was 62.5%. Most nurses agreed with the practice of
      withholding/withdrawing potentially life-prolonging treatments (93%), with
      decisions to alleviate symptoms with possible life-shortening side effects (96%)
      and with the practice of euthanasia (92%). Their support for the different
      decisions existed regardless of whether they had cared for terminally ill
      patients or not. Most nurses also thought that they have an important role to
      play especially in the ELD-making process. Nurses' views on their proper role in
      the administration of drugs in euthanasia and continuous deep sedation showed a
      large dispersal. Overall, nurses' work setting determines their opinions on
      nurses' role in ELDs. In conclusion, nurses accept a wide variety of ELDs being
      practiced with terminally ill patients.

PMID- 19605605
TI  - Prioritising drugs for single patient (n-of-1) trials in palliative care.
AB  - Many of the drugs prescribed commonly to palliative care patients have
      potentially significant side-effects and are of unproven benefit. The acquisition
      of evidence to support the prescribing of these drugs has been very slow. Single
      patient trials (SPTs) (also known as n-of-1 trials) offer a potential means of
      obtaining the evidence necessary to support or refute the use of several of the
      drugs and interventions whose use is currently based on physician experience or
      anecdote alone. A list of SPTs considered "most urgent", for commonly employed
      treatments and for the most common and most troublesome symptoms in palliative
      care is presented. These are drugs for which the gap between evidence and
      practice is greatest, where the evidence of efficacy is most lacking, where
      significant side effects potentially lead to the greatest morbidity, or where
      cost is a major patient burden. Although not all the drugs used in palliative
      care are suitable, SPTs provide a potential alternative method of gathering
      evidence in palliative care.

PMID- 19605607
TI  - Transitions for Clinical Nursing Research: an international journal.

PMID- 19605606
TI  - Patient demographics and learning needs: examination of relationship.
AB  - BACKGROUND: Limited research has examined differences in patients' learning needs
      in relation to demographic characteristics, such as age, gender, level of
      education, and culture. Yet such knowledge is essential to develop postoperative
      educational interventions that are tailored to patients' needs. STUDY PURPOSE:
      The purpose of this study was to examine the relationship between learning needs
      and the demographic characteristics of patients who have undergone coronary
      artery bypass graft (CABG) surgery. METHOD: A descriptive design was used.The
      sample of convenience included 38 patients who met eligibility criteria. MAJOR
      RESULTS: Statistically significant relationships were found between the patients'
      age, gender, and cultural background, and learning needs (p<.05) and not between
      the learning needs and level of education. APPLICATION: These preliminary
      highlight the importance of attending to learning needs of patients with
      different backgrounds in order to improve self-management following CABG surgery.

PMID- 19605608
TI  - Age, invasive ventilatory support and outcomes in elderly patients admitted to
      intensive care units.
AB  - BACKGROUND: although advancing age is associated with worse outcomes on
      mechanically ventilated elderly patients admitted to intensive care units (ICU),
      this relation has not been extensively investigated on patients not requiring
      invasive ventilatory support. OBJECTIVE: to determine the relationship between
      age and in-hospital mortality of elderly patients, admitted to ICU, requiring and
      not requiring invasive ventilatory support. DESIGN: prospective observational
      cohort study conducted over a period of 11 months. SETTING: medical-surgical ICU
      at a Brazilian university hospital. SUBJECTS: a total of 840 patients aged 55
      years and older were admitted to ICU. METHODS: in-hospital death rates for
      patients requiring and not requiring invasive ventilatory support were compared
      across three successive age intervals (55-64; 65-74 and 75 or more years),
      adjusting for severity of illness using the Acute Physiologic Score. RESULTS: age
      was strongly correlated with mortality among the invasively ventilated subgroup
      of patients and the multivariate adjusted odds ratios increased progressively
      with every age increment (OR = 1.60, 95% CI = 1.01-2.54 for 65-74 years old and
      OR = 2.68, 95% CI = 1.58-4.56 for > or =75 years). For the patients not submitted
      to invasive ventilatory support, age was not independently associated with in
      hospital mortality (OR = 2.28, 95% CI = 0.99-5.25 for 65-74 years old and OR =
      1.95, 95% CI = 0.82-4.62 for > or =75 years old). CONCLUSIONS: the combination of
      age and invasive mechanical ventilation is strongly associated with in-hospital
      mortality. Age should not be considered as a factor related to in-hospital
      mortality of elderly patients not requiring invasive ventilatory support in ICU.

PMID- 19605609
TI  - Contribution of hindpaw cutaneous inputs to the control of lateral stability
      during walking in the cat.
AB  - To delineate the role of cutaneous feedback from the paws in the regulation of
      balance during walking, we compared the corrective responses of cats to lateral
      support surface translation before and after cutaneous denervation of the
      hindpaws. In addition, we compared characteristics of undisturbed walking before
      and after denervation. Electromyographic and kinematic data were collected from
      three cats trained to walk across a walkway, the central portion of which could
      be unexpectedly translated laterally in either direction. Following denervation,
      all of the cats changed their step width, lowered their pelvis, and spent more
      time with the hindlegs in double-support when walking across the walkway. When
      displaced by lateral support surface translations, the denervated cats made
      larger lateral steps and required more than a single step to regain balance.
      However, none of the cats fell following the denervation. The appearance and
      latency of the responses evoked in the hindleg muscles by the perturbations were
      unaffected by the denervation. However, the amplitude of these responses was
      affected by the loss of cutaneous inputs. Responses evoked at paw contact were
      significantly reduced in most muscles in the absence of cutaneous input, whereas
      responses evoked at end of stance revealed significant increases in gluteus
      medius activity with little influence on the activity of other muscles. Therefore
      the loss of cutaneous inputs leads to instability during gait. Although cutaneous
      feedback from the hindpaws is not essential for triggering corrective responses
      to support surface disturbances, it appears that cutaneous inputs are important
      for scaling the responses initiated by other cues.

PMID- 19605610
TI  - Ocular responses to brief motion of textured backgrounds during smooth pursuit in
      humans.
AB  - We studied the effects of horizontal smooth pursuit on the ocular responses to
      brief vertical perturbations of textured backgrounds in humans. When the subject
      was fixating on a stationary target, a brief vertical perturbation of the
      background elicited a small tracking response. When the subject was pursuing a
      target moving horizontally, the same background perturbation elicited a larger
      response: that is, the response to vertical background perturbations was enhanced
      during pursuit (pursuit-related enhancement). On the other hand, the dependencies
      of the ocular responses on spatial frequency, temporal frequency, and stimulus
      contrast were similar regardless of the ongoing behavior of the subject. We also
      found that a low-level energy-based mechanism underlies the ocular responses to
      vertical perturbations of the background during fixation and smooth pursuit. We
      conclude that the pursuit-related enhancement is independent of the properties of
      visual processing for cross-axis motion of backgrounds, which suggests that this
      enhancement results from uniform facilitation of the visual system and/or from
      facilitation of visuomotor transmission downstream of the visual processing.

PMID- 19605611
TI  - Two distinct mechanisms mediate potentiating effects of depolarization on
      synaptic transmission.
AB  - Two distinct mechanisms mediate potentiating effects of depolarization on
      synaptic transmission. Recently there has been renewed interest in a type of
      plasticity in which a neuron's somatic membrane potential influences synaptic
      transmission. We study mechanisms that mediate this type of control at a synapse
      between a mechanoafferent, B21, and B8, a motor neuron that receives chemical
      synaptic input. Previously we demonstrated that the somatic membrane potential
      determines spike propagation within B21. Namely, B21 must be centrally
      depolarized if spikes are to propagate to an output process. We now demonstrate
      that this will occur with central depolarizations that are only a few millivolts.
      Depolarizations of this magnitude are not, however, sufficient to induce synaptic
      transmission to B8. B21-induced postsynaptic potentials (PSPs) are only observed
      if B21 is centrally depolarized by >or=10 mV. Larger depolarizations have a
      second impact on B21. They induce graded changes in the baseline intracellular
      calcium concentration that are virtually essential for the induction of chemical
      synaptic transmission. During motor programs, subthreshold depolarizations that
      increase calcium concentrations are observed during one of the two antagonistic
      phases of rhythmic activity. Chemical synaptic transmission from B21 to B8 is,
      therefore, likely to occur in a phase-dependent manner. Other neurons that
      receive mechanoafferent input are electrically coupled to B21. Differential
      control of spike propagation and chemical synaptic transmission may, therefore,
      represent a mechanism that permits selective control of afferent transmission to
      different types of neurons contacted by B21. Afferent transmission to neurons
      receiving chemical synaptic input will be phase specific, whereas transmission to
      electrically coupled followers will be phase independent.

PMID- 19605612
TI  - Inhibitory effect of somatostatin-14 on L-type voltage-gated calcium channels in
      cultured cone photoreceptors requires intracellular calcium.
AB  - The inhibitory effects of somatostatin have been well documented for many
      physiological processes. The action of somatostatin is through G-protein-coupled
      receptor-mediated second-messenger signaling, which in turn affects other
      downstream targets including ion channels. In the retina, somatostatin is
      released from a specific class of amacrine cells. Here we report that there was a
      circadian phase-dependent effect of somatostatin-14 (SS14) on the L-type voltage
      gated calcium channels (L-VGCCs) in cultured chicken cone photoreceptors, and our
      study reveals that this process is dependent on intracellular calcium stores.
      Application of 500 nM SS14 for 2 h caused a decrease in L-VGCC currents only
      during the subjective night but not the subjective day. We then explored the
      cellular mechanisms underlying the circadian phase-dependent effect of SS14. The
      inhibitory effect of SS14 on L-VGCCs was mediated through the pertussis-toxin
      sensitive G-protein-dependent somatostatin receptor 2 (sst2). Activation of sst2
      by SS14 further activated downstream signaling involving phospholipase C and
      intracellular calcium stores. Mobilization of intracellular Ca2+ was required for
      somatostatin induced inhibition of photoreceptor L-VGCCs, suggesting that
      somatostatin plays an important role in the modulation of photoreceptor
      physiology.

PMID- 19605613
TI  - Premotor interneurons in the local control of stepping motor output for the stick
      insect single middle leg.
AB  - In insect walking systems, nonspiking interneurons (NSIs) play an important role
      in the control of posture and movement. As such NSIs are known to contribute to
      state-dependent modifications in processing of proprioceptive signals from the
      legs. For example, NSIs process a flexion of the femur-tibia (FTi) joint signaled
      by the femoral chordotonal organ (fCO) such that the stance phase motor output is
      reinforced in the active locomotor system. This phenomenon representing a reflex
      reversal is the first part of the "active reaction" (AR) and was hypothesized to
      functionally represent a major control feature by which sensory feedback supports
      stance generation. As NSIs are known to contribute to the AR, the question
      arises, whether they serve similar functions during stepping and whether the AR
      is generally part of the control system for walking. We studied these issues in
      vivo, in a single leg preparation of Carausius morosus with the leg kinematics
      being confined to changes in one plane, along the coxa-trochanteral and the FTi
      joint. Following kinematic analysis, identified NSIs (E1-E8, I1, I2, and I4) were
      recorded intracellularly during single leg stepping at different velocities. We
      detected clear similarities between the activity pattern of NSIs during single
      leg stepping and their responses to fCO-stimulation during the generation of the
      AR. This strongly supports the notion that the motor output generated during the
      AR reflects part of the control regime for stepping. Furthermore, our experiments
      revealed that alterations in stepping velocity result from modifications in the
      activity of the premotor NSIs involved in stance phase generation.

PMID- 19605614
TI  - Changes in performance monitoring during sensorimotor adaptation.
AB  - Error detection and correction are essential components of motor skill learning.
      These processes have been well characterized in cognitive psychology using
      electroencephalography (EEG) to record an event-related potential (ERP) called
      error-related negativity (ERN). However, it is unclear whether this ERP component
      is sensitive to the magnitude of the error made in a sensorimotor adaptation
      task. In the present study, we tested the function of error-related activity in a
      visuomotor adaptation task. To examine whether error size is reflected in the
      ERP, two groups of participants adapted manual aiming movements to either a small
      (30 degrees) or large (45 degrees) rotation of the visual feedback display. Each
      participant's trials were sorted into large and small error trials using a median
      split to examine potential error magnitude waveform differences. We also examined
      these trial types at the early and late stages of adaptation. There were no group
      differences for the behavioral or neural measures; however, waveforms from large
      error trials were significantly different from small error trials. The waveforms
      also changed as a function of practice as early adaptation waveforms were larger
      than late adaptation waveforms. The observed ERP component reflected differences
      in error magnitude with the amount of activity corresponding to the size of the
      error. Movement monitoring potentials likely affected the frequency and time
      course of the waveform so that it did not resemble the typical ERN; however,
      error-related activity was still distinguishable. The present findings are
      discussed in terms of current theories of the ERN as well as skill acquisition.

PMID- 19605616
TI  - Statistics of natural movements are reflected in motor errors.
AB  - Humans use their arms to engage in a wide variety of motor tasks during everyday
      life. However, little is known about the statistics of these natural arm
      movements. Studies of the sensory system have shown that the statistics of
      sensory inputs are key to determining sensory processing. We hypothesized that
      the statistics of natural everyday movements may, in a similar way, influence
      motor performance as measured in laboratory-based tasks. We developed a portable
      motion-tracking system that could be worn by subjects as they went about their
      daily routine outside of a laboratory setting. We found that the well-documented
      symmetry bias is reflected in the relative incidence of movements made during
      everyday tasks. Specifically, symmetric and antisymmetric movements are
      predominant at low frequencies, whereas only symmetric movements are predominant
      at high frequencies. Moreover, the statistics of natural movements, that is,
      their relative incidence, correlated with subjects' performance on a laboratory
      based phase-tracking task. These results provide a link between natural movement
      statistics and motor performance and confirm that the symmetry bias documented in
      laboratory studies is a natural feature of human movement.

PMID- 19605615
TI  - Flexible learning of natural statistics in the human brain.
AB  - The ability to detect and identify targets in cluttered scenes is a critical
      skill for survival and interactions. To solve this challenge the brain has
      optimized mechanisms for capitalizing on frequently occurring regularities in the
      environment. Although evolution and development have been suggested to shape the
      brain's architecture in a manner that resembles these natural statistics, we
      provide novel evidence that short-term experience in adulthood may modify the
      brain's functional organization to support integration of signals atypical of
      shape contours in natural scenes. Although collinearity is a prevalent principle
      for perceptual integration in natural scenes, we show that observers learn to
      exploit other image regularities (i.e., orthogonal alignments of segments at an
      angle to the contour path) that typically signify discontinuities. Combining
      behavioral and functional MRI measurements, we demonstrate that this flexible
      learning is mediated by changes in the neural representations of behaviorally
      relevant image regularities primarily in dorsal visual areas. These changes in
      neural sensitivity are in line with changes in perceptual sensitivity for the
      detection of orthogonal contours and are evident only in observers that show
      significant performance improvement. In contrast, changes in the activation
      extent in frontoparietal regions are evident independent of performance changes,
      may support the detection of salient regions, and modulate perceptual integration
      in occipitotemporal areas in a top-down manner. Thus experience at shorter
      timescales in adulthood supports the adaptive functional optimization of visual
      circuits for flexible interpretation of natural scenes.

PMID- 19605619
TI  - CEO compensation and hospital financial performance.
AB  - Growing interest in pay-for-performance and the level of chief executive
      officers' (CEOs') pay raises questions about the link between performance and
      compensation in the health sector. This study compares the compensation of
      nonprofit hospital CEOs in Ontario, Canada to the three longest reported and most
      used measures of hospital financial performance. Our sample consisted of 132 CEOs
      from 92 hospitals between 1999 and 2006. Unbalanced panel data were analyzed
      using fixed effects regression. Results suggest that CEO compensation was largely
      unrelated to hospital financial performance. Inflation-adjusted salaries appeared
      to increase over time independent of hospital performance, and hospital size was
      positively correlated with CEO compensation. The apparent upward trend in salary
      despite some declines in financial performance challenges the fundamental
      assumption underlying this article, that is, financial performance is likely
      linked to CEO compensation in Ontario. Further research is needed to understand
      long-term performance related to compensation incentives.

PMID- 19605620
TI  - Review: Toward realizing the potential of diversity in composition of
      interprofessional health care teams: an examination of the cognitive and
      psychosocial dynamics of interprofessional collaboration.
AB  - Interprofessional approaches to health and social care have been linked to
      improved planning and policy development, more clinically effective services, and
      enhanced problem solving; however, there is evidence that professionals tend to
      operate in uniprofessional silos and that attempts to share knowledge across
      professional borders are often unsuccessful.

PMID- 19605621
TI  - Do hospitals rank differently on HCAHPS for different patient subgroups?
AB  - Prior research documents differences in patient-reported experiences by patient
      characteristics. Using nine measures of patient experience from 1,203,229
      patients discharged in 2006-2007 from 2,684 acute and critical access hospitals,
      the authors find that adjusted hospital scores measure distinctions in quality
      for the average patient with high reliability. The authors also find that
      hospital "ranks" (the relative scores of hospitals for patients of a given type)
      vary substantially by patient health status and race/ ethnicity/language, and
      moderately by patient education and age (p < .05 for almost all measures).
      Quality improvement efforts should examine hospital performance with both sicker
      and healthier patients, because many hospitals that do well with one group
      (relative to other hospitals) may not do well with another. The experiences of
      American Indians/Alaska Natives should also receive particular attention. As
      HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) data
      accumulate, reports that drill down to hospital performance for patient subtypes
      (especially by health status) may be valuable.

PMID- 19605622
TI  - Measuring exposure to health messages in community-based intervention studies: a
      systematic review of current practices.
AB  - Accurately measuring exposure is critical to all intervention studies. The
      present review examines the extent to which best practices in exposure assessment
      are adhered to in community-based prevention and education studies. A systematic
      literature review was conducted examining community-based studies testing
      communication interventions, published in 2003-2007. Of 663 studies identified,
      54 met all inclusion criteria and were reviewed for type of exposure assessment
      conducted (if any), use of exposure data in study analyses, and discussion of
      biases related to exposure assessment. Although a majority of studies (n = 38;
      70%) assessed exposure, most of these used only a simple dichotomous measure (n =
      31; 82%), less than half used exposure data to adjust intervention effects (n =
      16; 42%), and only six (16%) addressed selective exposure as a possible source of
      bias. There is substantial room for improvement in measurement and analysis of
      exposure to communication in community-based disease prevention studies.

PMID- 19605623
TI  - A comparison of web-based and paper-based survey methods: testing assumptions of
      survey mode and response cost.
AB  - Web-based surveys have become more prevalent in areas such as evaluation,
      research, and marketing research to name a few. The proliferation of these online
      surveys raises the question, how do response rates compare with traditional
      surveys and at what cost? This research explored response rates and costs for Web
      based surveys, paper surveys, and mixed-mode surveys. The participants included
      evaluators from the American Evaluation Association (AEA). Results included that
      mixed-mode, while more expensive, had higher response rates.

PMID- 19605624
TI  - Does asynchronous neuronal activity average out on a macroscopic scale?

PMID- 19605625
TI  - ON inputs to the OFF layer: bipolar cells that break the stratification rules of
      the retina.
AB  - The vertebrate retina is a distinctly laminar structure. Functionally, the inner
      plexiform layer, in which bipolar cells synapse onto amacrine and ganglion cells,
      is subdivided into two sublaminae. Cells that depolarize at light offset ramify
      in sublamina a; those that depolarize at light onset ramify in sublamina b. The
      separation of ON and OFF pathways appears to be a fundamental principle of
      retinal organization that is reflected throughout the entire visual system. We
      show three clear exceptions to this rule, in which the axons of calbindin
      positive ON cone bipolar cells make ribbon synapses as they pass through the OFF
      layers with three separate cell types: (1) dopaminergic amacrine cells, (2)
      intrinsically photosensitive ganglion cells, and (3) bistratified diving ganglion
      cells. The postsynaptic location of the AMPA receptor GluR4 at these sites
      suggests that ON bipolar cells can make functional synapses as their axons pass
      through the OFF layers of the inner plexiform layer. These findings resolve a
      long-standing question regarding the anomalous ON inputs to dopaminergic amacrine
      cells and suggest that certain ON bipolar cell axons can break the stratification
      rules of the inner plexiform layer by providing significant synaptic output
      before their terminal specializations. These outputs are not only to dopaminergic
      amacrine cells but also to at least two ON ganglion cell types that have
      dendrites that arborize in sublamina a.

PMID- 19605626
TI  - BMI1 sustains human glioblastoma multiforme stem cell renewal.
AB  - Glioblastoma multiforme (GBM) is one of the most common and aggressive types of
      brain tumors. In GBM, a subpopulation of CD133-positive cancer initiating cells
      displays stem cell characteristics. The Polycomb group (PcG) and oncogene BMI1 is
      part of the Polycomb repressive complex 1 (PRC1) that regulates gene expression
      by modifying chromatin organization. Here we show that BMI1 is expressed in human
      GBM tumors and highly enriched in CD133-positive cells. Stable BMI1 knockdown
      using short hairpin RNA-expressing lentiviruses resulted in inhibition of
      clonogenic potential in vitro and of brain tumor formation in vivo. Cell biology
      studies support the notion that BMI1 prevents CD133-positive cell apoptosis
      and/or differentiation into neurons and astrocytes, depending on the cellular
      context. Gene expression analyses suggest that BMI1 represses alternate tumor
      suppressor pathways that attempt to compensate for INK4A/ARF/P53 deletion and
      PI(3)K/AKT hyperactivity. Inhibition of EZH2, the main component of the PRC2,
      also impaired GBM tumor growth. Our results reveal that PcG proteins are involved
      in GBM tumor growth and required to sustain cancer initiating stem cell renewal.

PMID- 19605627
TI  - Heritability of intracortical inhibition and facilitation.
AB  - The present twin study investigates heritability of motor cortex excitability,
      measured by the paired pulse transcranial magnetic stimulation technique.
      Specifically, intracortical facilitation (ICF) and inhibition (ICI) and
      corticospinal excitability were tested in monozygotic (MZ), dizygotic (DZ), and
      unrelated pairs (UP). Robust ICF and ICI effects were found, with a higher
      similarity of MZ than DZ and UP pairs. Heritability estimates (h(2)) were 0.80
      for ICI and 0.92 for ICF. However, corticospinal excitability did not show
      significant differences between MZ and DZ pairs, whereas both significantly
      differed from UP. Hence, the study provides--for the first time--a clear evidence
      of heritable individual differences in motor cortex excitability.

PMID- 19605628
TI  - BDNF-mediated cerebellar granule cell development is impaired in mice null for
      CaMKK2 or CaMKIV.
AB  - The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in
      the brain where they play important roles in activating intracellular responses
      to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via
      these kinases during brain development, we have examined cerebellar development
      in mice null for CaMKK2 or CaMKIV. Here, we demonstrate that CaMKK2/CaMKIV
      dependent phosphorylation of cAMP response element-binding protein (CREB)
      correlates with Bdnf transcription, which is required for normal development of
      cerebellar granule cell neurons. We show in vivo and in vitro that the absence of
      either CaMKK2 or CaMKIV disrupts the ability of developing cerebellar granule
      cells in the external granule cell layer to cease proliferation and begin
      migration to the internal granule cell layer. Furthermore, loss of CaMKK2 or
      CaMKIV results in decreased CREB phosphorylation (pCREB), Bdnf exon I and IV
      containing mRNAs, and brain-derived neurotrophic factor (BDNF) protein in
      cerebellar granule cell neurons. Reexpression of CaMKK2 or CaMKIV in granule
      cells that lack CaMKK2 or CaMKIV, respectively, restores pCREB and BDNF to wild
      type levels and addition of BDNF rescues granule cell migration in vitro. These
      results reveal a previously undefined role for a CaMKK2/CaMKIV cascade involved
      in cerebellar granule cell development and show specifically that Ca(2+)
      dependent regulation of BDNF through CaMKK2/CaMKIV is required for this process.

PMID- 19605629
TI  - Netrin-DCC, Robo-Slit, and heparan sulfate proteoglycans coordinate lateral
      positioning of longitudinal dopaminergic diencephalospinal axons.
AB  - Longitudinal axons provide connectivity between remote areas of the nervous
      system. Although the molecular determinants driving commissural pathway formation
      have been well characterized, mechanisms specifying the formation of longitudinal
      axon tracts in the vertebrate nervous system are largely unknown. Here, we study
      axon guidance mechanisms of the longitudinal dopaminergic (DA) diencephalospinal
      tract. This tract is established by DA neurons located in the ventral
      diencephalon and is thought to be involved in modulating locomotor activity.
      Using mutant analysis as well as gain of function and loss of function
      experiments, we demonstrate that longitudinal DA axons navigate by integrating
      long-range signaling of midline-derived cues. Repulsive Robo2/Slit signaling
      keeps longitudinal DA axons away from the midline. In the absence of repulsive
      Robo2/Slit function, DA axons are attracted toward the midline by DCC (deleted in
      colorectal cancer)/Netrin1 signaling. Thus, Slit-based repulsion counteracts
      Netrin-mediated attraction to specify lateral positions of the DA
      diencephalospinal tract. We further identified heparan sulfate proteglycans as
      essential modulators of DA diencephalospinal guidance mechanisms. Our findings
      provide insight into the complexity of positioning far-projecting longitudinal
      axons and allow us to provide a model for DA diencephalospinal pathfinding.
      Simultaneous integrations of repulsive and attractive long-range cues from the
      midline act in a concerted manner to define lateral positions of DA longitudinal
      axon tracts.

PMID- 19605630
TI  - Transcriptome profiling reveals TGF-beta signaling involvement in
      epileptogenesis.
AB  - Brain injury may result in the development of epilepsy, one of the most common
      neurological disorders. We previously demonstrated that albumin is critical in
      the generation of epilepsy after blood-brain barrier (BBB) compromise. Here, we
      identify TGF-beta pathway activation as the underlying mechanism. We demonstrate
      that direct activation of the TGF-beta pathway by TGF-beta1 results in
      epileptiform activity similar to that after exposure to albumin.
      Coimmunoprecipitation revealed binding of albumin to TGF-beta receptor II, and
      Smad2 phosphorylation confirmed downstream activation of this pathway.
      Transcriptome profiling demonstrated similar expression patterns after BBB
      breakdown, albumin, and TGF-beta1 exposure, including modulation of genes
      associated with the TGF-beta pathway, early astrocytic activation, inflammation,
      and reduced inhibitory transmission. Importantly, TGF-beta pathway blockers
      suppressed most albumin-induced transcriptional changes and prevented the
      generation of epileptiform activity. Our present data identifies the TGF-beta
      pathway as a novel putative epileptogenic signaling cascade and therapeutic
      target for the prevention of injury-induced epilepsy.

PMID- 19605631
TI  - Vestibular signals in macaque extrastriate visual cortex are functionally
      appropriate for heading perception.
AB  - Visual and vestibular signals converge onto the dorsal medial superior temporal
      area (MSTd) of the macaque extrastriate visual cortex, which is thought to be
      involved in multisensory heading perception for spatial navigation. Peripheral
      otolith information, however, is ambiguous and cannot distinguish linear
      accelerations experienced during self-motion from those resulting from changes in
      spatial orientation relative to gravity. Here we show that, unlike peripheral
      vestibular sensors but similar to lobules 9 and 10 of the cerebellar vermis
      (nodulus and uvula), MSTd neurons respond selectively to heading and not to
      changes in orientation relative to gravity. In support of a role in heading
      perception, MSTd vestibular responses are also dominated by velocity-like
      temporal dynamics, which might optimize sensory integration with visual motion
      information. Unlike the cerebellar vermis, however, MSTd neurons also carry a
      spatial orientation-independent rotation signal from the semicircular canals,
      which could be useful in compensating for the effects of head rotation on the
      processing of optic flow. These findings show that vestibular signals in MSTd are
      appropriately processed to support a functional role in multisensory heading
      perception.

PMID- 19605634
TI  - Single-cell and population coding of expected reward probability in the
      orbitofrontal cortex of the rat.
AB  - The orbitofrontal cortex (OFC) has been implicated in decision-making under
      uncertainty, but it is unknown how information about the probability or
      uncertainty of future reward is coded by single orbitofrontal neurons and
      ensembles. We recorded neuronal ensembles in rat OFC during an olfactory
      discrimination task in which different odor stimuli predicted different reward
      probabilities. Single-unit firing patterns correlated to the expected reward
      probability primarily within an immobile waiting period before reward delivery
      but also when the rat executed movements toward the reward site. During these pre
      reward periods, a subset of OFC neurons was sensitive to differences in
      probability but only very rarely discriminated on the basis of reward
      uncertainty. In the reward period, neurons responded during presentation or
      omission of reward or during both types of outcome. At the population level,
      neurons were characterized by a wide divergence in firing-rate variability
      attributable to expected probability. A population analysis using template
      matching as reconstruction method indicated that OFC generates a distributed
      representation of reward probability with a weak dependence on neuronal group
      size. The analysis furthermore confirmed that predictive information coded by OFC
      populations was quantitatively related to reward probability, but not to
      uncertainty.

PMID- 19605633
TI  - "Referred visual sensations": rapid perceptual elongation after visual cortical
      deprivation.
AB  - Visual perceptual distortion (i.e., elongation) has been demonstrated in a single
      case study after several months of cortical deprivation after a stroke. Here we
      asked whether similar perceptual elongation can be observed in healthy
      participants after deprivation and, crucially, how soon after deprivation this
      elongation occurs. To answer this question, we patched one eye, thus
      noninvasively and reversibly depriving bottom-up input to the region of primary
      visual cortex (V1) corresponding to the blind spot (BS) in the unpatched eye, and
      tested whether and how quickly elongation occurs after the onset of deprivation.
      Within seconds of eye patching, participants perceived rectangles adjacent to the
      BS to be elongated toward the BS. We attribute this perceptual elongation to
      rapid receptive field expansion within the deprived V1 as reported in
      electrophysiological studies after retinal lesions and refer to it as "referred
      visual sensations" (RVS). This RVS is too fast to be the result of structural
      changes in the cortex (e.g., the growth of new connections), instead implicating
      unmasking of preexisting connections as the underlying neural mechanism. These
      findings may shed light on other reported perceptual distortions, as well as the
      phenomena of "filling-in."

PMID- 19605632
TI  - Regulation of early neurite morphogenesis by the Na+/H+ exchanger NHE1.
AB  - The ubiquitously expressed Na(+)/H(+) exchanger NHE1 plays an important role in
      regulating polarized membrane protrusion and directional motility in non-neuronal
      cells. Using NGF-differentiated PC12 cells and murine neocortical neurons in
      vitro, we now show that NHE1 plays a role in regulating early neurite
      morphogenesis. NHE1 was expressed in growth cones in which it gave rise to an
      elevated intracellular pH in actively extending neurites. The NHE1 inhibitor
      cariporide reversibly reduced growth cone filopodia number and the formation and
      elongation of neurites, especially branches, whereas the transient overexpression
      of full-length NHE1, but not NHE1 mutants deficient in either ion translocation
      activity or actin cytoskeletal anchoring, elicited opposite effects. In addition,
      compared with neocortical neurons obtained from wild-type littermates, neurons
      isolated from NHE1-null mice exhibited reductions in early neurite outgrowth, an
      effect that was rescued by overexpression of full-length NHE1 but not NHE1
      mutants. Finally, the growth-promoting effects of netrin-1, but not BDNF or IGF
      1, were markedly reduced by cariporide in wild-type neocortical neurons and were
      not observed in NHE1-null neurons. Although netrin-1 failed to increase growth
      cone intracellular pH or Na(+)/H(+) exchange activity, netrin-1-induced increases
      in early neurite outgrowth were restored in NHE1-null neurons transfected with
      full-length NHE1 but not an ion translocation-deficient mutant. Collectively, the
      results indicate that NHE1 participates in the regulation of early neurite
      morphogenesis and identify a novel role for NHE1 in the promotion of early
      neurite outgrowth by netrin-1.

PMID- 19605635
TI  - Differential dopaminergic modulation of neostriatal synaptic connections of
      striatopallidal axon collaterals.
AB  - Recent studies have demonstrated that GABAergic synaptic transmission among
      neostriatal spiny projection neurons (SPNs) is strongly modulated by dopamine
      with individual connections exhibiting either D(1) receptor (D(1)R)-mediated
      facilitation or D(2) receptor (D(2)R)-mediated inhibition and, at least in some
      preparations, a subset of connections exhibiting both of these effects. In light
      of the cell type-specific expression of D(1a)R in striatonigral and D(2)R in
      striatopallidal neurons and the differential expression of the other D(1) and
      D(2) family dopamine receptors, we hypothesize that the nature of the
      dopaminergic modulation is specific to the types of SPNs that participate in the
      connection. Here the biophysical properties and dopaminergic modulation of
      intrastriatal connections formed by striatopallidal neurons were examined.
      Contrary to previous expectation, synapses formed by striatopallidal neurons were
      biophysically and pharmacologically heterogeneous. Two distinct types of axon
      collateral connections could be distinguished among striatopallidal neurons. The
      more common, small-amplitude connections (80%) exhibited mean IPSC amplitudes
      several times smaller than their less frequent large-amplitude counterparts,
      principally because of a smaller number of release sites involved. The two types
      of connections were also differentially regulated by dopamine. Small-amplitude
      connections exhibited strong and exclusively D(2)R-mediated presynaptic
      inhibition, whereas large-amplitude connections were unresponsive to dopamine.
      Synaptic connections from striatopallidal to striatonigral neurons exhibited
      exclusively D(2)R-mediated presynaptic inhibition that was similar to the
      regulation of small-amplitude connections between pairs of striatopallidal cells.
      Together, these findings demonstrate a previously unrecognized complexity in the
      organization and dopaminergic control of synaptic communication among SPNs.

PMID- 19605636
TI  - Neocortical disynaptic inhibition requires somatodendritic integration in
      interneurons.
AB  - In his theory of functional polarity, Ramon y Cajal first identified the soma and
      dendrites as the principal recipient compartments of a neuron and the axon as its
      main output structure. Despite notable exceptions in other parts of the nervous
      system (Schoppa and Urban, 2003; Wassle, 2004; Howard et al., 2005), this route
      of signal propagation has been shown to underlie the functional properties of
      most neocortical circuits studied so far. Recent evidence, however, suggests that
      neocortical excitatory cells may trigger the release of the inhibitory
      neurotransmitter GABA by directly depolarizing the axon terminals of inhibitory
      interneurons, thus bypassing their somatodendritic compartments (Ren et al.,
      2007). By using a combination of optical and electrophysiological approaches, we
      find that synaptically released glutamate fails to trigger GABA release through a
      direct action on GABAergic terminals under physiological conditions. Rather, our
      evidence suggests that glutamate triggers GABA release only after somatodendritic
      depolarization and action potential generation at GABAergic interneurons. These
      data indicate that neocortical inhibition is recruited by classical
      somatodendritic integration rather than direct activation of interneuron axon
      terminals.

PMID- 19605637
TI  - Responses to static visual images in macaque lateral geniculate nucleus:
      implications for adaptation, negative afterimages, and visual fading.
AB  - Adaptation to static scenes is a familiar and fundamental aspect of visual
      perception that causes negative afterimages, fading, and many other visual
      illusions. To establish a foundation for understanding the neuronal bases of such
      phenomena and to constrain the contributions of retinal versus cortical
      processing, we studied the responses of neurons in the dorsal lateral geniculate
      nucleus during and after the presentation of prolonged static visual stimuli. We
      found that parvocellular (P) cells (the more numerous and color-sensitive
      pathway) showed response adaptation with a time constant on the order of tens of
      seconds and that their response after the removal of a visual stimulus lasting 1
      min was similar in amplitude and time course to the response evoked by the
      photographic negative stimulus. Magnocellular (M) cells (the faster-conducting
      and achromatic pathway) had after responses that were substantially weaker than
      responses evoked by patterned visual stimuli. This difference points to the
      existence of an adaptive mechanism in the P-pathway that is absent or impaired in
      the M-pathway and is inconsistent with full adaptation of photoreceptors, which
      feed both pathways. Cells in both pathways often maintained a substantial tonic
      response throughout 1 min stimuli, suggesting that these major feedforward inputs
      to cortex adapt too slowly to account for visual fading. Our findings suggest
      that faster-adapting mechanisms in cortex are likely to be required to account
      for the dynamics of perception during and after the viewing of prolonged static
      images.

PMID- 19605639
TI  - Three patterns of oscillatory activity differentially synchronize developing
      neocortical networks in vivo.
AB  - Coordinated patterns of electrical activity are important for the early
      development of sensory systems. The spatiotemporal dynamics of these early
      activity patterns and the role of the peripheral sensory input for their
      generation are essentially unknown. We performed extracellular multielectrode
      recordings in the somatosensory cortex of postnatal day 0 to 7 rats in vivo and
      observed three distinct patterns of synchronized oscillatory activity. (1)
      Spontaneous and periphery-driven spindle bursts of 1-2 s in duration and
      approximately 10 Hz in frequency occurred approximately every 10 s. (2)
      Spontaneous and sensory-driven gamma oscillations of 150-300 ms duration and 30
      40 Hz in frequency occurred every 10-30 s. (3) Long oscillations appeared only
      every approximately 20 min and revealed the largest amplitude (250-750 microV)
      and longest duration (>40 s). These three distinct patterns of early oscillatory
      activity differently synchronized the neonatal cortical network. Whereas spindle
      bursts and gamma oscillations did not propagate and synchronized a local neuronal
      network of 200-400 microm in diameter, long oscillations propagated with 25-30
      microm/s and synchronized 600-800 microm large ensembles. All three activity
      patterns were triggered by sensory activation. Single electrical stimulation of
      the whisker pad or tactile whisker activation elicited neocortical spindle bursts
      and gamma activity. Long oscillations could be only evoked by repetitive sensory
      stimulation. The neonatal oscillatory patterns in vivo depended on NMDA receptor
      mediated synaptic transmission and gap junctional coupling. Whereas spindle
      bursts and gamma oscillations may represent an early functional columnar-like
      pattern, long oscillations may serve as a propagating activation signal
      consolidating these immature neuronal networks.

PMID- 19605638
TI  - Mitochondria are the source of hydrogen peroxide for dynamic brain-cell
      signaling.
AB  - Hydrogen peroxide (H(2)O(2)) is emerging as a ubiquitous small-molecule messenger
      in biology, particularly in the brain, but underlying mechanisms of peroxide
      signaling remain an open frontier for study. For example, dynamic dopamine
      transmission in dorsolateral striatum is regulated on a subsecond timescale by
      glutamate via H(2)O(2) signaling, which activates ATP-sensitive potassium
      (K(ATP)) channels to inhibit dopamine release. However, the origin of this
      modulatory H(2)O(2) has been elusive. Here we addressed three possible sources of
      H(2)O(2) produced for rapid neuronal signaling in striatum: mitochondrial
      respiration, monoamine oxidase (MAO), and NADPH oxidase (Nox). Evoked dopamine
      release in guinea-pig striatal slices was monitored with carbon-fiber
      microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence
      imaging of H(2)O(2) and tissue analysis of ATP, we found that coapplication of
      rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a
      complex II substrate, limited H(2)O(2) production, but maintained tissue ATP
      content. Strikingly, coapplication of rotenone and succinate also prevented
      glutamate-dependent regulation of dopamine release, implicating mitochondrial
      H(2)O(2) in release modulation. In contrast, inhibitors of MAO or Nox had no
      effect on dopamine release, suggesting a limited role for these metabolic enzymes
      in rapid H(2)O(2) production in the striatum. These data provide the first
      demonstration that respiring mitochondria are the primary source of H(2)O(2)
      generation for dynamic neuronal signaling.

PMID- 19605641
TI  - Reduction of the rate of protein translation in patients with myotonic dystrophy
      2.
AB  - Myotonic dystrophy 2 (DM2) is an autosomal dominant, multisystem disease, which
      primarily affects skeletal muscle. DM2 is caused by CCTGn expansion in the intron
      1 of the ZNF9 gene. Expression of the mutant CCUGn RNA changes RNA processing in
      patients with DM2; however, the role of ZNF9 protein in DM2 pathology has been
      not elucidated. ZNF9 has been shown to regulate cap-dependent and cap-independent
      translation. We have examined a possible role of ZNF9 in the regulation of
      translation in DM2 patients. We found that ZNF9 interacts with the 5' UTRs of
      terminal oligopyrimidine (TOP) tract mRNAs encoding human ribosomal protein,
      RPS17, poly(A)-binding protein 1 (PABP1), and the elongation factors, eEF1A and
      eEF2. The binding activity of ZNF9 toward these TOP-containing 5' UTRs is reduced
      in DM2 muscle. Consistent with the reduction of this activity, the levels of
      RPS17, PABP, eEF1A, and eEF2 proteins are also diminished in DM2 muscle. The
      reduction of ZNF9 RNA-binding activity in DM2 correlates with a decrease of ZNF9
      protein levels in cytoplasm of DM2 muscle cells. We found that the reduction of
      ZNF9 is caused by expression of the mutant CCUG repeats. This decrease of
      proteins of translational apparatus in DM2 correlates with a reduction of a rate
      of protein synthesis in myoblasts from DM2 patients. We found that the ectopic
      expression of ZNF9 in DM2 myoblasts corrects rate of protein synthesis,
      suggesting that the alterations in CCUG-ZNF9-TOP mRNAs pathway are responsible
      for the reduction of the rate of protein translation in DM2 muscle cells.

PMID- 19605642
TI  - The foveal confluence in human visual cortex.
AB  - The human visual system devotes a significant proportion of its resources to a
      very small part of the visual field, the fovea. Foveal vision is crucial for
      natural behavior and many tasks in daily life such as reading or fine motor
      control. Despite its significant size, this part of cortex is rarely investigated
      and the limited data have resulted in competing models of the layout of the
      foveal confluence in primate species. Specifically, how V2 and V3 converge at the
      central fovea is the subject of debate in primates and has remained "terra
      incognita" in humans. Using high-resolution fMRI (1.2 x 1.2 x 1.2 mm(3)) and
      carefully designed visual stimuli, we sought to accurately map the human foveal
      confluence and hence disambiguate the competing theories. We find that V1, V2,
      and V3 are separable right into the center of the foveal confluence, and V1 ends
      as a rounded wedge with an affine mapping of the foveal singularity. The adjacent
      V2 and, in contrast to current concepts from macaque monkey, also V3 maps form
      continuous bands (approximately 5 mm wide) around the tip of V1. This mapping
      results in a highly anisotropic representation of the visual field in these
      areas. Unexpectedly, for the centermost 0.75 degrees, the cortical
      representations for both V2 and V3 are larger than that of V1, indicating that
      more neuronal processing power is dedicated to second-level analysis in this
      small but important part of the visual field.

PMID- 19605640
TI  - NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal
      plasticity to sleep loss.
AB  - A loss in the necessary amount of sleep alters expression of genes and proteins
      implicated in brain plasticity, but key proteins that render neuronal circuits
      sensitive to sleep disturbance are unknown. We show that mild (4-6 h) sleep
      deprivation (SD) selectively augmented the number of NR2A subunits of NMDA
      receptors on postsynaptic densities of adult mouse CA1 synapses. The greater
      synaptic NR2A content facilitated induction of CA3-CA1 long-term depression in
      the theta frequency stimulation range and augmented the synaptic modification
      threshold. NR2A-knock-out mice maintained behavioral response to SD, including
      compensatory increase in post-deprivation resting time, but hippocampal synaptic
      plasticity was insensitive to sleep loss. After SD, the balance between
      synaptically activated and slowly recruited NMDA receptor pools during temporal
      summation was disrupted. Together, these results indicate that NR2A is obligatory
      for the consequences of sleep loss on hippocampal synaptic plasticity. These
      findings could advance pharmacological strategies aiming to sustain hippocampal
      function during sleep restriction.

PMID- 19605643
TI  - Proactive inhibitory control and attractor dynamics in countermanding action: a
      spiking neural circuit model.
AB  - Flexible behavior depends on the brain's ability to suppress a habitual response
      or to cancel a planned movement whenever needed. Such inhibitory control has been
      studied using the countermanding paradigm in which subjects are required to
      withhold an imminent movement when a stop signal appears infrequently in a
      fraction of trials. To elucidate the circuit mechanism of inhibitory control of
      action, we developed a recurrent network model consisting of spiking movement
      (GO) neurons and fixation (STOP) neurons, based on neurophysiological
      observations in the frontal eye field and superior colliculus of behaving
      monkeys. The model places a premium on the network dynamics before the onset of a
      stop signal, especially the experimentally observed high baseline activity of
      fixation neurons, which is assumed to be modulated by a persistent top-down
      control signal, and their synaptic interaction with movement neurons. The model
      simulated observed neural activity and fit behavioral performance quantitatively.
      In contrast to a race model in which the STOP process is initiated at the onset
      of a stop signal, in our model whether a movement will eventually be canceled is
      determined largely by the proactive top-down control and the stochastic network
      dynamics, even before the appearance of the stop signal. A prediction about the
      correlation between the fixation neural activity and the behavioral outcome was
      verified in the neurophysiological data recorded from behaving monkeys. The
      proposed mechanism for adjusting control through tonically active neurons that
      inhibit movement-producing neurons has significant implications for exploring the
      basis of impulsivity associated with psychiatric disorders.

PMID- 19605644
TI  - Enhanced visual motion perception in major depressive disorder.
AB  - Major depressive disorder (MDD) is a mood disorder that is not traditionally
      considered to affect the visual system. However, recent findings have reported
      decreased cortical levels of the inhibitory neurotransmitter GABA in occipital
      cortex. To explore possible functional consequences of MDD on visual processing,
      we applied a psychophysical visual motion processing task in which healthy young
      adults typically exhibit impaired perceptual discrimination of large high
      contrast stimuli. It has been suggested that this phenomenon, spatial
      suppression, is mediated by GABAergic center-surround antagonism in visual
      pathways. Based on previous findings linking MDD to occipital GABA dysfunction,
      we hypothesized that MDD patients would exhibit decreased spatial suppression,
      leading to the counterintuitive hypothesis of better psychophysical performance.
      Indeed, motion perception for typically suppressed stimuli was enhanced in
      patients with MDD compared with age-matched controls. Furthermore, the degree of
      spatial suppression correlated with an individual's illness load; patients with
      greater lifetime duration of depression exhibited the least spatial suppression
      and performed the best in the high-contrast motion discrimination task. Notably,
      this decrease in spatial suppression persisted beyond recovery and without the
      confound of acute illness or treatment; all patients had been clinically
      recovered and unmedicated for several months at the time of testing, suggesting
      that depression has ubiquitous consequences that may persist long after mood
      symptoms have receded. This finding raises the possibility that spatial
      suppression may represent a sensitive endophenotypic marker of trait
      vulnerability in MDD.

PMID- 19605645
TI  - Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin
      receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3
      fatty acids and curcumin.
AB  - Both insulin resistance (type II diabetes) and beta-amyloid (Abeta) oligomers are
      implicated in Alzheimer's disease (AD). Here, we investigate the role of Abeta
      oligomer-induced c-Jun N-terminal kinase (JNK) activation leading to
      phosphorylation and degradation of the adaptor protein insulin receptor substrate
      1 (IRS-1). IRS-1 couples insulin and other trophic factor receptors to downstream
      kinases and neuroprotective signaling. Increased phospho-IRS-1 is found in AD
      brain and insulin-resistant tissues from diabetics. Here, we report Abeta
      oligomers significantly increased active JNK and phosphorylation of IRS-1
      (Ser616) and tau (Ser422) in cultured hippocampal neurons, whereas JNK inhibition
      blocked these responses. The omega-3 fatty acid docosahexaenoic acid (DHA)
      similarly inhibited JNK and the phosphorylation of IRS-1 and tau in cultured
      hippocampal neurons. Feeding 3xTg-AD transgenic mice a diet high in saturated and
      omega-6 fat increased active JNK and phosphorylated IRS-1 and tau. Treatment of
      the 3xTg-AD mice on high-fat diet with fish oil or curcumin or a combination of
      both for 4 months reduced phosphorylated JNK, IRS-1, and tau and prevented the
      degradation of total IRS-1. This was accompanied by improvement in Y-maze
      performance. Mice fed with fish oil and curcumin for 1 month had more significant
      effects on Y-maze, and the combination showed more significant inhibition of JNK,
      IRS-1, and tau phosphorylation. These data indicate JNK mediates Abeta oligomer
      inactivation of IRS-1 and phospho-tau pathology and that dietary treatment with
      fish oil/DHA, curcumin, or a combination of both has the potential to improve
      insulin/trophic signaling and cognitive deficits in AD.

PMID- 19605646
TI  - Impaired balance of mitochondrial fission and fusion in Alzheimer's disease.
AB  - Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD)
      neurons. In this study, we explored the involvement of an abnormal mitochondrial
      dynamics by investigating the changes in the expression of mitochondrial fission
      and fusion proteins in AD brain and the potential cause and consequence of these
      changes in neuronal cells. We found that mitochondria were redistributed away
      from axons in the pyramidal neurons of AD brain. Immunoblot analysis revealed
      that levels of DLP1 (also referred to as Drp1), OPA1, Mfn1, and Mfn2 were
      significantly reduced whereas levels of Fis1 were significantly increased in AD.
      Despite their differential effects on mitochondrial morphology, manipulations of
      these mitochondrial fission and fusion proteins in neuronal cells to mimic their
      expressional changes in AD caused a similar abnormal mitochondrial distribution
      pattern, such that mitochondrial density was reduced in the cell periphery of M17
      cells or neuronal process of primary neurons and correlated with reduced spine
      density in the neurite. Interestingly, oligomeric amyloid-beta-derived diffusible
      ligands (ADDLs) caused mitochondrial fragmentation and reduced mitochondrial
      density in neuronal processes. More importantly, ADDL-induced synaptic change
      (i.e., loss of dendritic spine and postsynaptic density protein 95 puncta)
      correlated with abnormal mitochondrial distribution. DLP1 overexpression, likely
      through repopulation of neuronal processes with mitochondria, prevented ADDL
      induced synaptic loss, suggesting that abnormal mitochondrial dynamics plays an
      important role in ADDL-induced synaptic abnormalities. Based on these findings,
      we suggest that an altered balance in mitochondrial fission and fusion is likely
      an important mechanism leading to mitochondrial and neuronal dysfunction in AD
      brain.

PMID- 19605648
TI  - Modulation of cerebellar excitability by polarity-specific noninvasive direct
      current stimulation.
AB  - The cerebellum is a crucial structure involved in movement control and cognitive
      processing. Noninvasive stimulation of the cerebellum results in
      neurophysiological and behavioral changes, an effect that has been attributed to
      modulation of cerebello-brain connectivity. At rest, the cerebellum exerts an
      overall inhibitory tone over the primary motor cortex (M1), cerebello-brain
      inhibition (CBI), likely through dentate-thalamo-cortical connections. The level
      of excitability of this pathway before and after stimulation of the cerebellum,
      however, has not been directly investigated. In this study, we used transcranial
      magnetic stimulation to determine changes in M1, brainstem, and CBI before and
      after 25 min of anodal, cathodal, or sham transcranial direct current stimulation
      (tDCS) applied over the right cerebellar cortex. We hypothesized that anodal tDCS
      would result in an enhancement of CBI and cathodal would decrease it, relative to
      sham stimulation. We found that cathodal tDCS resulted in a clear decrease of
      CBI, whereas anodal tDCS increased it, in the absence of changes after sham
      stimulation. These effects were specific to the cerebello-cortical connections
      with no changes in other M1 or brainstem excitability measures. The cathodal
      effect on CBI was found to be dependent on stimulation intensity and lasted up to
      30 min after the cessation of tDCS. These results suggest that tDCS can modulate
      in a focal and polarity-specific manner cerebellar excitability, likely through
      changes in Purkinje cell activity. Therefore, direct current stimulation of the
      cerebellum may have significant potential implications for patients with
      cerebellar dysfunction as well as to motor control studies.

PMID- 19605649
TI  - Amygdala activation predicts gaze toward fearful eyes.
AB  - The human amygdala can be robustly activated by presenting fearful faces, and it
      has been speculated that this activation has functional relevance for redirecting
      the gaze toward the eye region. To clarify this relationship between amygdala
      activation and gaze-orienting behavior, functional magnetic resonance imaging
      data and eye movements were simultaneously acquired in the current study during
      the evaluation of facial expressions. Fearful, angry, happy, and neutral faces
      were briefly presented to healthy volunteers in an event-related manner. We
      controlled for the initial fixation by unpredictably shifting the faces downward
      or upward on each trial, such that the eyes or the mouth were presented at
      fixation. Across emotional expressions, participants showed a bias to shift their
      gaze toward the eyes, but the magnitude of this effect followed the distribution
      of diagnostically relevant regions in the face. Amygdala activity was
      specifically enhanced for fearful faces with the mouth aligned to fixation, and
      this differential activation predicted gazing behavior preferentially targeting
      the eye region. These results reveal a direct role of the amygdala in reflexive
      gaze initiation toward fearfully widened eyes. They mirror deficits observed in
      patients with amygdala lesions and open a window for future studies on patients
      with autism spectrum disorder, in which deficits in emotion recognition, probably
      related to atypical gaze patterns and abnormal amygdala activation, have been
      observed.

PMID- 19605647
TI  - Loss of Hsp70 exacerbates pathogenesis but not levels of fibrillar aggregates in
      a mouse model of Huntington's disease.
AB  - Endogenous protein quality control machinery has long been suspected of
      influencing the onset and progression of neurodegenerative diseases characterized
      by accumulation of misfolded proteins. Huntington's disease (HD) is a fatal
      neurodegenerative disorder caused by an expansion of a polyglutamine (polyQ)
      tract in the protein huntingtin (htt), which leads to its aggregation and
      accumulation in inclusion bodies. Here, we demonstrate in a mouse model of HD
      that deletion of the molecular chaperones Hsp70.1 and Hsp70.3 significantly
      exacerbated numerous physical, behavioral and neuropathological outcome measures,
      including survival, body weight, tremor, limb clasping and open field activities.
      Deletion of Hsp70.1 and Hsp70.3 significantly increased the size of inclusion
      bodies formed by mutant htt exon 1, but surprisingly did not affect the levels of
      fibrillar aggregates. Moreover, the lack of Hsp70s significantly decreased levels
      of the calcium regulated protein c-Fos, a marker for neuronal activity. In
      contrast, deletion of Hsp70s did not accelerate disease in a mouse model of
      infectious prion-mediated neurodegeneration, ruling out the possibility that the
      Hsp70.1/70.3 mice are nonspecifically sensitized to all protein misfolding
      disorders. Thus, endogenous Hsp70s are a critical component of the cellular
      defense against the toxic effects of misfolded htt protein in neurons, but buffer
      toxicity by mechanisms independent of the deposition of fibrillar aggregates.

PMID- 19605651
TI  - Informatics in radiology: integration of the medical imaging resource center into
      a teaching hospital network to allow single sign-on access.
AB  - The RSNA Medical Imaging Resource Center (MIRC) software is an open-source
      program that allows users to identify, index, and retrieve images, teaching
      files, and other radiologic data that share a common underlying structure. The
      software is being continually improved as new challenges and different needs
      become apparent. Although version T30 is easily installed on a stand-alone
      computer, its implementation at healthcare enterprises with complex network
      architecture may be challenging with respect to security because users cannot log
      on by using a standard enterprise-wide authentication protocol. Instead,
      authentication takes place through the local MIRC database, creating security
      concerns and potential organizational problems. In this setting, the Lightweight
      Directory Access Protocol (LDAP) can be used to provide a single sign-on
      environment and increase authentication security. A commercial directory service
      using LDAP has been successfully integrated with MIRC in a large multifacility
      enterprise to provide single sign-on capability compatible with the institutional
      networking policies for password security.

PMID- 19605650
TI  - Postsynaptic mechanisms govern the differential excitation of cortical neurons by
      thalamic inputs.
AB  - Thalamocortical (TC) afferents relay sensory input to the cortex by making
      synapses onto both excitatory regular-spiking principal cells (RS cells) and
      inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial
      role in coordinating excitation with inhibition during the earliest steps of
      somatosensory processing in the cortex. Although the same TC afferents contact
      both FS and RS cells, FS cells receive larger and faster excitatory inputs from
      individual TC afferents. Here, we show that this larger thalamic excitation of FS
      cells occurs via GluR2-lacking AMPA receptors (AMPARs), and results from a
      fourfold larger quantal amplitude compared with the thalamic inputs onto RS
      cells. Thalamic afferents also activate NMDA receptors (NMDARs) at synapses onto
      both cells types, yet RS cell NMDAR currents are slower and pass more current at
      physiological membrane potentials. Because of these synaptic specializations,
      GluR2-lacking AMPARs selectively maintain feedforward inhibition of RS cells,
      whereas NMDARs contribute to the spiking of RS cells and hence to cortical
      recurrent excitation. Thus, thalamic afferent activity diverges into two routes
      that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate
      the dynamic balance of excitation and inhibition as sensory input enters the
      cortex.

PMID- 19605652
TI  - Imaging of posttransplantation lymphoproliferative disorder after solid organ
      transplantation.
AB  - Posttransplantation lymphoproliferative disorders (PTLDs) are a heterogeneous
      group of diseases that represent uncommon complications of transplantation and
      can lead to significant morbidity and mortality. PTLD is most prevalent during
      the first year following transplantation and occurs most frequently in multiorgan
      transplant recipients, followed by bowel, heart-lung, and lung recipients. It may
      involve any of the organ systems, with disease manifestation and the anatomic
      pattern of organ involvement being highly dependent on the type of
      transplantation. The current classification system includes four subtypes that
      have different prognoses requiring different treatment strategies. Tissue
      sampling is necessary for diagnosis and further subcategorization. The majority
      of cases are characterized by B-cell proliferation and are related to infection
      from Epstein-Barr virus. Knowledge of the distribution and radiologic features of
      PTLD allows the radiologist to play a pivotal role in making an early diagnosis
      and in guiding biopsy.

PMID- 19605653
TI  - A clinical and radiologic review of uncommon types and causes of pancreatitis.
AB  - Acute pancreatitis is one of the most common conditions for which emergent
      imaging is indicated. Alcohol consumption and cholelithiasis are the most common
      causes of acute pancreatitis in adults, whereas the majority of cases in children
      are idiopathic or secondary to trauma. A wide variety of structural and
      biochemical abnormalities may also cause pancreatitis. Although in some cases it
      is difficult to identify the specific cause of the disease radiologically,
      certain uncommon types of acute or chronic pancreatitis may have unique imaging
      features that can help the radiologist make an accurate diagnosis. These unusual
      types include autoimmune pancreatitis, groove pancreatitis, tropical
      pancreatitis, hereditary pancreatitis, and pancreatitis in ectopic or heterotopic
      pancreatic tissue. Pancreatitis may occasionally be seen in association with
      cystic fibrosis or pancreas divisum, or secondary to worm infestation of the
      pancreaticobiliary tree (eg, by Ascaris lumbricoides). In addition, primary
      pancreatic and duodenal masses may occasionally manifest as acute or recurrent
      acute pancreatitis. Knowledge of the classic imaging findings of these entities
      allows prompt recognition of the relevant pathologic condition, thereby
      preventing misdiagnosis and subsequent inappropriate or delayed management.

PMID- 19605654
TI  - Normal variants of the cerebral circulation at multidetector CT angiography.
AB  - Multidetector computed tomographic (CT) angiography is used in many institutions
      for initial evaluation of the cerebral circulation for acute stroke and
      subarachnoid hemorrhage as well as in various preoperative settings. A
      comprehensive CT examination that includes a review of three-dimensional and
      maximum intensity projection images of the intra- and extracranial arteries and
      axial images of the skull base (obtained with bone window settings) allows
      identification of most abnormalities and normal variants. Knowledge of the
      presence and clinical relevance of normal variants such as fenestrations,
      duplications, and persistent fetal arteries plays a crucial role in the diagnosis
      and management of acute stroke and subarachnoid hemorrhage and may aid in
      surgical planning. For example, the preoperative detection of a medial or
      intrasellar persistent trigeminal artery may help surgeons avoid a potentially
      life-threatening hemorrhage in a patient undergoing transsphenoidal surgery for
      pituitary adenoma. However, the significance of normal variants diverges widely:
      A clinically important association has been observed between fenestration and
      intracranial aneurysm formation, whereas early branching of the middle cerebral
      artery is not associated with an increased risk of aneurysm formation and has
      little clinical significance. Supplemental material available at
      http://radiographics.rsnajnls.org/cgi/content/full/29/4/1027/DC1.

PMID- 19605655
TI  - Appearance of normal cranial nerves on steady-state free precession MR images.
AB  - As radiologic imaging technology improves and more intricate details of the
      anatomy can be evaluated, images provide more precise diagnostic information and
      allow better localization of abnormalities. For example, standard T2-weighted
      magnetic resonance (MR) imaging sequences adequately depicted only the larger
      cranial nerves, whereas current steady-state free precession (SSFP) sequences are
      capable of depicting the cisternal segments of all 12 cranial nerves. SSFP
      sequences provide submillimetric spatial resolution and high contrast resolution
      between cerebrospinal fluid and solid structures, allowing the reconstruction of
      elegant multiplanar images that highlight the course of each nerve. These
      sequences have become a mainstay in the evaluation of the cerebellopontine angles
      and inner ear. Usually referred to by their trade names or acronyms (eg,
      constructive interference steady state, or CISS, and fast imaging employing
      steady-state acquisition, or FIESTA), SSFP sequences allow precise
      differentiation between branches of the facial and vestibulocochlear nerves,
      accurate detection of small masses in the cerebellopontine angles and internal
      auditory canals, and detailed evaluation of endolymph and perilymph within the
      inner ear. To take full advantage of these imaging sequences, radiologists must
      be familiar with the appearances of similar anatomic details of all 12 cranial
      nerves on SSFP MR images.

PMID- 19605657
TI  - Fistulas in malignant gynecologic disease: etiology, imaging, and management.
AB  - A fistula that occurs in association with a malignancy of the female reproductive
      tract may be caused by a primary or recurrent tumor or may be a complication of
      surgery or radiation therapy. Identification of the cause, complexity, and
      location of a fistula is essential for optimal management planning. Radiologic
      imaging, particularly with computed tomography and magnetic resonance techniques,
      is invaluable for the assessment of gynecologic fistulas and may help direct the
      clinician toward the most appropriate management pathway. The modality and
      technique selected for the initial imaging evaluation depend largely on the
      clinical history and manifestations. However, imaging with a combination of
      techniques often is required for accurate diagnosis and effective treatment
      planning. Radiologists should be familiar with suggestive clinical signs and
      symptoms as well as with the characteristic appearances of rectovaginal,
      vesicovaginal, ureterovaginal, enterovesical, enterocutaneous, and other pelvic
      fistulas at multimodality imaging.

PMID- 19605656
TI  - Pearls and pitfalls of MR lymphography in gynecologic malignancy.
AB  - Dissemination of tumor to lymph nodes is one of the principal routes of
      metastatic disease. The presence or absence of nodal disease is an important
      prognostic factor in gynecologic malignancies; thus, nodal staging is an integral
      part of the pretreatment assessment. It is vital that pretreatment nodal staging
      be accurate and reliable. Current imaging techniques such as computed tomography
      and magnetic resonance (MR) imaging have limitations because they rely almost
      exclusively on size criteria. MR lymphography uses a lymph node-specific contrast
      agent (ferumoxtran-10) composed of ultrasmall superparamagnetic iron oxide
      particles. The contrast agent is taken up by macrophages within benign lymph
      nodes and allows differentiation from malignant nodes on the basis of alterations
      in signal intensity. This technique has been shown to increase the sensitivity
      and specificity of detection of lymph node metastases independent of nodal size.
      However, as with any technique, there are pitfalls that the radiologist must be
      aware of to avoid interpretative errors.

PMID- 19605658
TI  - Mullerian duct anomalies and mimics in children and adolescents: correlative
      intraoperative assessment with clinical imaging.
AB  - Mullerian duct anomalies (MDAs) are congenital entities that result from
      nondevelopment, defective vertical or lateral fusion, or resorption failure of
      the mullerian (paramesonephric) ducts. MDAs are common, although the majority are
      asymptomatic, and have been classified by the American Society of Reproductive
      Medicine according to clinical manifestations, prognosis, and treatment. Accurate
      diagnosis of an MDA is essential, since the management approach varies depending
      on the type of malformation. In females, when a mullerian duct becomes
      obstructed, the patient may present with an abdominal mass and dysmenorrhea. If
      the patient is not treated in a timely fashion, the consequences can be severe,
      extending even to infertility. When an MDA is suspected, ultrasonography (US)
      should be performed initially to delineate any abnormalities in the genital
      tract. However, US cannot help identify the type of MDA. In contrast, magnetic
      resonance imaging is a valuable technique for noninvasive evaluation of the
      female pelvic anatomy and accurate MDA classification. If obstruction is present,
      surgical correction of the MDA may be required, and further counseling of the
      patient with regard to reproductive possibilities becomes important. Supplemental
      material available at
      http://radiographics.rsnajnls.org/cgi/content/full/29/4/1085/DC1.

PMID- 19605659
TI  - Imaging of the seminal vesicle and vas deferens.
AB  - The seminal vesicle (SV) and vas deferens (VD) are ancillary but essential
      urogenital organs. Understanding their embryologic features and anatomy can be
      helpful in evaluating various disorders of these organs. Recently, cross
      sectional imaging modalities, including ultrasonography, computed tomography, and
      magnetic resonance (MR) imaging, have been increasingly used for evaluation of
      the SV and VD. The development of these organs is closely related to that of
      urinary organs, including the kidneys and ureters. Frequently, unilateral SV
      agenesis is associated with renal agenesis, and bilateral SV or VD agenesis is
      associated with mutations of the cystic fibrosis gene. Congenital SV cysts are
      commonly associated with ipsilateral renal agenesis or dysgenesis. These
      congenital anomalies can be well evaluated with MR imaging. Inflammation, post
      radiation therapy changes, and amyloidosis of the SV appear as diffuse wall
      thickening and may mimic tumor invasion by prostate cancer. Primary neoplasms
      involving the SV and VD are extremely rare, whereas secondary neoplasms are much
      more common. Carcinoma from the prostate, bladder, or rectum can directly invade
      the SV and VD. Typical MR imaging findings of such invasion include a low-signal
      intensity mass on T2-weighted images or soft-tissue thickening in the SV or VD
      along with loss of normal architecture.

PMID- 19605660
TI  - Practice corner: swine flu in 2009: what does the future hold?

PMID- 19605661
TI  - Lymphoscintigraphy in cutaneous melanoma: an updated total body atlas of sentinel
      node mapping.
AB  - Lymphoscintigraphy has become part of the standard of care for patients with a
      new or recurrent diagnosis of melanoma, in helping determine the status of
      regional lymph nodes. Correct identification of sentinel lymph nodes enables the
      surgeon to further delineate the extent of malignancy by allowing sampling of the
      appropriate nodal group. Performing the lymphoscintigraphy prior to the planned
      operation allows limited surgery with less extensive postoperative morbidity. For
      this reason, a thorough knowledge of the lymph node drainage patterns from the
      different primary tumor locations, as well as of proper lymphoscintigraphic
      techniques and radiopharmaceuticals, constitutes an important armamentarium in
      the hands of surgeons, radiologists, and nuclear medicine physicians.

PMID- 19605662
TI  - Emergency joint aspiration: a guide for radiologists on call.
AB  - Septic arthritis is a disabling and possibly life-threatening disease that
      requires early diagnosis for optimal management. It is important that clinical
      and imaging features of septic arthritis be promptly identified. In addition,
      because other disease entities may have characteristics similar to those of
      septic arthritis, analysis of a needle biopsy specimen may be necessary for
      differential diagnosis. Radiologists may be asked to perform emergent aspiration
      of a possibly infected joint. It is important that those who perform aspiration
      procedures be familiar with a safe and effective imaging-guided arthrocentesis
      technique that is tailored to the individual patient and the specific joint
      affected.

PMID- 19605663
TI  - Imaging of chronic recurrent multifocal osteomyelitis.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder
      of children and young adults that is characterized by nonbacterial osteomyelitis.
      Patients typically present with multifocal bone pain secondary to sterile osseous
      inflammation, and the disease has a relapsing and remitting course. The cause of
      CRMO remains unclear, although the results of several studies have suggested a
      genetic component. The typical imaging findings of CRMO include lytic and
      sclerotic lesions in the metaphyses of long bones and the medial clavicles. Other
      common sites of disease are the vertebral bodies, pelvis, ribs, and mandible.
      CRMO is often bilateral and multifocal at presentation. Owing to the lack of a
      diagnostic test, CRMO remains a diagnosis of exclusion. Although generally a self
      limiting disease, CRMO can have a prolonged course and result in significant
      morbidity. Radiologists can be the first to suggest this diagnosis given its
      characteristic radiographic appearance and distribution of disease. Radiologists
      should be familiar with the typical imaging findings of CRMO to prevent
      unnecessary multiple biopsies and long-term antibiotic treatment in children with
      CRMO.

PMID- 19605664
TI  - US artifacts.
AB  - Image artifacts are commonly encountered in clinical ultrasonography (US) and may
      be a source of confusion for the interpreting physician. Some artifacts may be
      avoidable and arise secondary to improper scanning technique. Other artifacts are
      generated by the physical limitations of the modality. US artifacts can be
      understood with a basic appreciation of the physical properties of the ultrasound
      beam, the propagation of sound in matter, and the assumptions of image
      processing. US artifacts arise secondary to errors inherent to the ultrasound
      beam characteristics, the presence of multiple echo paths, velocity errors, and
      attenuation errors. The beam width, side lobe, reverberation, comet tail, ring
      down, mirror image, speed displacement, refraction, attenuation, shadowing, and
      increased through-transmission artifacts are encountered routinely in clinical
      practice. Recognition of these artifacts is important because they may be clues
      to tissue composition and aid in diagnosis. The ability to recognize and remedy
      potentially correctable US artifacts is important for image quality improvement
      and optimal patient care.

PMID- 19605665
TI  - Scenes from the past: multidetector CT study of gallbladder stones in a wrapped
      Egyptian mummy.
AB  - A whole-body examination was performed with multidetector computed tomography
      (CT) of a completely wrapped Egyptian mummy from the collection at the Egyptian
      Museum in Turin, Italy. The mummy dates from the Eighteenth Dynasty. Although
      embalmment of the deceased man should have included evisceration in accordance
      with his social rank, no canopic jars containing internal organs had been found
      at the discovery of his tomb, and at CT, all the organs were found to have
      desiccated inside the body. Numerous calcified stones that were incidentally
      identified in the gallbladder had attenuation characteristics indicative of a
      predominant bile pigment content. This case demonstrates the superior
      capabilities of multidetector CT for the noninvasive study of embalmed bodies.
      The intrinsic capacity of CT for depicting the density of materials allowed not
      only the identification of the gallbladder stones but also their
      characterization.

PMID- 19605666
TI  - Best cases from the AFIP: juvenile ossifying fibroma of the calvaria.

PMID- 19605667
TI  - Best cases from the AFIP: cerebral toxoplasmosis.

PMID- 19605668
TI  - Best cases from the AFIP: multiple gastric carcinoids.

PMID- 19605669
TI  - Increased spontaneous but decreased mitogen-stimulated expression and excretion
      of interleukin 18 by mononuclear cells in patients with active systemic lupus
      erythematosus.
AB  - OBJECTIVE: To measure serum concentration and analyze the expression of
      interleukin 18 (IL-18) mRNA in mononuclear cells of patients with systemic lupus
      erythematosus (SLE). METHODS: IL-18 concentrations in sera and culture
      supernatants of peripheral blood mononuclear cells (PBMC) from healthy controls
      and patients with active SLE were measured by ELISA. PBMC and polymorphonuclear
      leukocytes (PMN) purified from patients with active SLE were stimulated with
      phytohemagglutinin (PHA), pokeweed mitogen (PWM), and lipopolysaccharide (LPS).
      Expression of IL-18 mRNA in cells was analyzed by RT-PCR. RESULTS: Serum IL-18
      levels were significantly higher in SLE patients than in controls, and correlated
      with disease activity in SLE patients (r(2) = 0.602). Two patients receiving
      intravenous methylprednisolone therapy (1.0 g/day for 3 days) showed profound
      decreases in serum IL-18 levels after therapy. The quiescent PBMC from SLE
      patients (30/30) expressed IL-18 transcript more frequently than control PBMC
      (20/30). PBMC from SLE patients produced more IL-18 than control PBMC after 72
      hours of incubation, by RT-PCR. PHA and PWM inhibited the production of IL-18 in
      PBMC from both SLE patients and controls. Inhibition by PWM was more pronounced
      than that by PHA, especially in SLE-PBMC. Control and SLE-PMN with or without LPS
      stimulation produced negligible IL-18. CONCLUSION: IL-18 is involved in the
      autoimmune derangement of leukocyte function in patients with active SLE.

PMID- 19605670
TI  - Improvement of severe systemic sclerosis-associated gastric antral vascular
      ectasia following immunosuppressive treatment with intravenous cyclophosphamide.
AB  - OBJECTIVE: We describe 3 patients with systemic sclerosis (SSc) with severe,
      transfusion-dependent gastric antral vascular ectasia (GAVE) refractory to laser
      ablation who showed remarkable clinical and endoscopic improvement following
      intravenous (IV) pulse cyclophosphamide (CYC) treatment. METHODS: Review of
      clinical records and upper gastrointestinal endoscopy images from 3 patients with
      SSc and severe GAVE before and after treatment with IV pulse CYC. RESULTS: IV CYC
      was followed by improvement and stabilization of hemoglobin levels, and marked
      reduction in blood transfusion requirements and the number and frequency of
      endoscopic laser treatments. CONCLUSION: IV pulse CYC immunosuppression was
      followed by remarkable clinical and endoscopic improvement of SSc-associated
      GAVE.

PMID- 19605671
TI  - Risk factors for the development of osteoporosis and osteoporotic fractures among
      older men.
AB  - OBJECTIVE: Osteoporotic fractures are associated with significant morbidity and
      mortality particularly among older men. However, there is little information
      regarding risk factors among this population. The aims of our study were to
      determine risk factors for osteoporosis and fragility fractures and the
      predictive value of bone mineral density (BMD) measurements for development of
      fragility fractures in a cohort of elderly Caucasian and African American men.
      METHODS: We evaluated 257 men aged 70 years or older for risk factors for
      osteoporosis and fragility fractures using a detailed questionnaire and BMD
      assessment. Exclusion criteria included conditions known to cause osteoporosis
      such as hypogonadism and chronic steroid use, current treatment with
      bisphosphonates, bilateral hip arthroplasties, and inability to ambulate
      independently. RESULTS: Age, weight, weight loss, androgen deprivation treatment,
      duration of use of dairy products, exercise, and fracture within 10 years prior
      to study entry were associated with osteoporosis (p < or = 0.05). Fragility
      fractures were associated with duration of use of dairy products, androgen
      deprivation treatment, osteoporosis, and history of fracture within 10 years
      prior to BMD assessment (p < or = 0.05). There were some differences in risk
      factors between the Caucasian and African American populations, suggesting that
      risk factors may vary between ethnic groups. CONCLUSION: Although men with
      osteoporosis had a higher rate of fractures, the majority of fractures occurred
      in men with T-scores > -2.5 standard deviations below the mean, suggesting that
      factors other than BMD are also important in determining risk.

PMID- 19605672
TI  - The association with the -159C/T polymorphism in the promoter region of the CD14
      gene and juvenile idiopathic arthritis in a Chinese Han population.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is generally considered to be
      caused by interaction of genetic and environmental factors. We investigated the
      association of a C-to-T transition in the promoter region of the CD14 gene on
      chromosome 5q31.1 and JIA in a Chinese Han population. METHODS: One hundred sixty
      three children with JIA and 281 healthy children (age- and sex-matched to JIA
      group) were studied. Polymerase chain reaction-restriction fragment-length
      polymorphism (PCR-RFLP) was used for analysis of the genotypes. (Trial
      registration number ChiCTR-CCC-00000312.) RESULTS: CD14 promoter-159 genotype
      frequencies of CC, CT, and TT were 11.48%, 49.18%, and 39.34%, respectively, in
      the systemic onset JIA group; 21.62%, 43.24%, and 35.14%, in the polyarticular
      JIA group; 16.67%, 50%, and 33.33%, in the oligoarticular JIA group; 6.9%,
      75.86%, and 17.24%, in the group with other types of JIA; and 37.01%, 46.98%, and
      16.01%, in the control group. Genotype frequency and allele frequency
      distribution were in accord with Hardy-Weinberg equilibrium. There were
      statistically significant differences in frequencies of genotype and allele in
      CD14 C-159T polymorphism between JIA group and control group (genotype: chi
      squared = 33.168, p < 0.05, CT vs CC, OR 2.946, 95% CI 1.739-4.990; TT vs CC, OR
      5.426, 95% CI 2.977-9.891. Allele: chi-squared = 33.168, p < 0.05, T vs C, OR
      2.251, 95% CI 1.704-2.973). The T allele frequencies of boys and girls were
      significantly higher than those in the control group (p < 0.001 of both).
      CONCLUSION: CD14 gene promoter C-159T polymorphism is significantly correlated
      with JIA in the Chinese Han population. The T allele of the C-159T polymorphism
      of CD14 gene may be a genetic risk factor for JIA.

PMID- 19605673
TI  - The prevalence of nephrolithiasis in patients with primary gout: a cross
      sectional study using helical computed tomography.
AB  - OBJECTIVE: To investigate the prevalence of nephrolithiasis in gouty patients by
      computed tomography (CT) imaging and to compare it with the "prevalence" of
      urolithiasis calculated from histories of urinary tract calculus. METHODS: The
      kidneys of 383 male patients with primary gout were examined using an unenhanced
      2-row helical CT detector, imaging at 2 mm collimation and a helical pitch of 3.
      The urolithiasis history of the 383 patients was investigated by inquiry.
      Patients' ages, body mass index, and laboratory data from a 1-hour clearance test
      were determined. RESULTS: CT scans confirmed nephrolithiasis in 103 (26.9%, 95%
      confidence interval 22.5%-31.6%) of the 383 gouty patients, and history of
      urinary calculus was positive in 65 (17.0%, 95% confidence interval 13.4%-21.1%)
      of the 383. However, 64 (62%) of the 103 stone-formers identified by CT had no
      history of urolithiasis. There was a significant difference between the ages of
      the 103 stone-formers identified by CT and the 65 stone-formers identified from
      the history. CONCLUSION: The prevalence of nephrolithiasis obtained using CT was
      26.9% in the 383 patients with primary gout. Our results imply that we cannot
      determine an accurate prevalence of urolithiasis from a patient's history. Most
      of the "prevalence" reported in the past may not correspond to a statistically
      justifiable one, but instead to the "cumulative incidence" during the contraction
      period of gout. Thus, the prevalence of nephrolithiasis confirmed by a cross
      sectional method and the "prevalence" of urolithiasis calculated from patients'
      calculus histories should be clearly distinguished.

PMID- 19605674
TI  - Serum CXCL16 concentrations correlate with the extent of skin sclerosis in
      patients with systemic sclerosis.
AB  - OBJECTIVE: To determine serum concentrations of soluble CXCL16 and its clinical
      associations in patients with systemic sclerosis (SSc). METHODS: Serum CXCL16
      levels from 89 patients with SSc were examined by ELISA. In a retrospective
      longitudinal study, 68 sera from 28 patients with SSc were analyzed (followup 1.3
      to 7.3 yrs). RESULTS: Serum CXCL16 levels were elevated in patients with SSc
      compared with healthy controls (n = 42). Patients with diffuse cutaneous SSc (n =
      52) had higher levels of CXCL16 than those with limited cutaneous SSc (n = 37).
      Serum CXCL16 levels correlated positively with the extent of skin sclerosis. In
      the longitudinal study, CXCL16 levels generally decreased on a parallel with the
      improvement in skin sclerosis. CONCLUSION: CXCL16 levels were increased in
      patients with SSc, and correlated with the extent of skin sclerosis, suggesting
      that CXCL16 may have a role in the development of skin fibrosis in SSc. Blockade
      of CXCL16 interaction might be a potential therapeutic target in patients with
      SSc.

PMID- 19605675
TI  - African Americans and Whites are equally appropriate to be considered for total
      joint arthroplasty.
AB  - OBJECTIVE: Ethnic disparities in the use of total joint arthroplasty (TJA) may be
      attributed to differences in the clinical appropriateness to undergo TJA. We
      sought to determine if racial differences in clinical appropriateness for surgery
      existed among a sample of primary care clinic patients with moderately to
      severely symptomatic knee or hip osteoarthritis (OA). METHODS: We used the cross
      sectional data of 684 patients who are potential candidates for TJA. Using a
      validated TJA appropriateness algorithm, an appropriateness factor was derived
      using the following variables: age (50-70 or > 70 yrs), Charlson comorbidity (<
      or = 1 or > 1), Western Ontario and McMaster Universities OA Index (WOMAC) pain
      and physical function, and adequacy of previous medical management. We used
      logistic regression to estimate the association of race with the dichotomous
      outcome of clinical appropriateness for TJA consideration. RESULTS: Sample
      consisted of 425 (62%) whites and 260 (38%) African Americans; 532 (78%) had knee
      OA and 153 (22%) had hip OA. The mean age was 64 +/- 9 years and the mean body
      mass index was 33.6 +/- 8 kg/m(2). The mean overall WOMAC score was 56 +/- 14
      (range 30-96), suggesting moderately severe OA. There were no significant racial
      group differences (p = 0.3) in the proportions of those deemed clinically
      appropriate for TJA. After controlling for potential confounders, race was not a
      predictor of clinical appropriateness for TJA (odds ratio 1.2, 95% confidence
      interval 0.8-1.8, p = 0.3). CONCLUSION: African Americans and whites were equally
      appropriate to be considered for TJA.

PMID- 19605676
TI  - Static knee alignment measurements among Caucasians and African Americans: the
      Johnston County Osteoarthritis Project.
AB  - OBJECTIVE: To determine if knee alignment measures differ between African
      Americans and Caucasians without radiographic knee osteoarthritis (rOA). METHODS:
      A single knee was randomly selected from 175 participants in the Johnston County
      Osteoarthritis Project without rOA in either knee. Anatomic axis, condylar,
      tibial plateau, and condylar plateau angles were measured by 1 radiologist; means
      were compared and adjusted for age and body mass index (BMI). RESULTS: There were
      no significant differences in knee alignment measurements between Caucasians and
      African Americans among men or women. CONCLUSION: Observed differences in knee
      rOA occurrence between African Americans and Caucasians are not explained by
      differences in static knee alignment.

PMID- 19605677
TI  - High prevalence of asymptomatic vertebral fractures in Chinese women with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the prevalence of vertebral fractures and to identify
      risk factors associated with vertebral fractures in Chinese women with systemic
      lupus erythematosus (SLE). METHODS: One hundred fifty-two consecutive patients
      with SLE were recruited in this cross-sectional study. Bone mineral density (BMD)
      measurements of the hip and spine were performed using the same dual energy X-ray
      absorptiometry (DEXA). Lateral radiographs of the spine (T5-L4) were assessed for
      vertebral fractures using a method described by Genant. Inflammatory and
      biochemical markers included C-reactive protein, receptor activator of nuclear
      factor-kappaB ligand, serum ss-CrossLaps assay for C-terminal telopeptides of
      type 1 collagen, and osteoprotegerin (OPG). RESULTS: Asymptomatic vertebral
      fractures occurred in 20.4% of patients with SLE. Univariate analyses of
      variables associated with fractures were older age, higher body mass index (BMI),
      lower BMD spine, lower BMD hips, higher serum C3 and C4, longer estrogen
      exposure, higher levels of OPG, and the use of sunscreen. Multivariate analysis
      showed older age (p = 0.017), higher BMI (p < 0.036), and lower BMD of the spine
      were significantly associated with vertebral fractures in the thoracic and/or
      lumbar spine (odds ratio 1.068, 1.166, 0.005; p = 0.018, p = 0.025, p = 0.003,
      respectively). CONCLUSION: Asymptomatic vertebral fractures occur in 20.4% of
      patients with SLE and 30% of these patients have normal BMD. The current method
      using DEXA to predict the presence of vertebral fracture has limited value and
      there is a need for assessment of bone quality. Vertebral morphometry in patients
      with SLE is recommended and early therapeutic intervention is necessary to
      prevent vertebral fractures in patients with SLE.

PMID- 19605678
TI  - Increased prevalence of antibodies to thyroid peroxidase in dry eyes and mouth
      syndrome or sicca asthenia polyalgia syndrome.
AB  - OBJECTIVE: A subset of patients presenting with sicca features suggestive of
      primary Sjogren's syndrome (pSS) do not fulfill diagnostic or histopathological
      criteria. This presentation was previously designated as dry eyes and mouth
      syndrome (DEMS) or sicca asthenia polyalgia syndrome (SAPS). We sought to define
      the underlying clinical, laboratory, and histological features of these patients.
      METHODS: The study population consisted of 27 consecutive patients with
      DEMS/SAPS; 54 patients with pSS served as controls. Medical charts were
      retrospectively evaluated for clinical and serological data and frozen sera were
      tested for the presence of antibodies against HIV, hepatitis C virus, and thyroid
      antigens. Immunohistochemical analysis of paraffin embedded tissues was also
      performed. RESULTS: Sicca symptoms and nonspecific musculoskeletal pain were the
      commonest clinical features of patients with DEMS/SAPS; positive titers of
      antibodies against thyroid peroxidase was the main underlying abnormality found
      in 16 out of 27 (59.2%) of patients with DEMS/SAPS compared to 11 out of 54
      (20.4%) of pSS controls (p = 0.0009). Histological analysis of the minor salivary
      gland (MSG) biopsies of patients with DEMS/SAPS disclosed a mild inflammatory
      infiltration of the interstitial tissue with a predominantly perivascular
      distribution. CONCLUSION: Patients with DEMS/SAPS present with sicca features and
      nonspecific musculoskeletal complaints, have high prevalence of antithyroid
      antibodies, and their MSG biopsies demonstrate a mild interstitial lymphocytic
      infiltration with a predominantly perivascular distribution. In the setting of
      clinical practice, we propose that in the presence of DEMS/SAPS testing for
      antithyroid antibody should be performed.

PMID- 19605679
TI  - Cartilage oligomeric matrix protein in patients with juvenile idiopathic
      arthritis: relation to growth and disease activity.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a
      prognostic marker of progressive joint destruction in rheumatoid arthritis. In
      this population based study we evaluated associations between plasma
      concentrations of COMP, disease activity, and growth velocity in patients with
      recent-onset juvenile idiopathic arthritis (JIA). COMP levels in JIA and healthy
      children were compared with those in healthy adults. Plasma levels of insulin
      like growth factor I (IGF-1), which has been associated with COMP expression and
      growth velocity, were studied in parallel. METHODS: 87 patients with JIA entered
      the study, including oligoarticular JIA (n = 34), enthesitis-related arthritis (n
      = 8), polyarticular rheumatoid factor (RF)-positive JIA (n = 2), polyarticular RF
      negative JIA (n = 27), systemic JIA (n = 6), and undifferentiated JIA (n = 10).
      Plasma levels of COMP were measured by ELISA and IGF-1 by a radioimmunoassay.
      RESULTS: Significantly higher COMP levels [mean 18.9 U/l (95% CI 17.3-20.5)] were
      found in healthy children compared with healthy adults [mean 10.7 U/l (95% CI 9.4
      12.1)] (p < 0.0001). COMP levels in the JIA patients [mean 13.5 U/l (95% CI 12.4
      14.7)] were significantly reduced compared to healthy children (p < 0.0001), and
      correlated negatively with C-reactive protein (CRP; r = -0.29, p = 0.01) and
      thrombocyte count (r = -0.28, p = 0.02). COMP levels in the JIA patients
      correlated positively with growth velocity (cm/yr) (r = 0.38, p = 0.0003) and
      growth velocity (SDS) (r = 0.29, p = 0.007). CONCLUSION: We found reduced COMP
      levels in children with JIA compared with healthy children. COMP levels in JIA
      correlated negatively with inflammatory activity as evaluated by CRP and the
      thrombocyte counts, and were associated with reduced growth rate.

PMID- 19605680
TI  - Quantitative epigenetics: DNA sequence variation need not apply.
AB  - Two recent reports, including one by Reinders and colleagues (pp. 939-950) in the
      April 15, 2009, issue of Genes & Development, describe the construction of
      Arabidopsis recombinant inbred populations that maximize epigenetic rather than
      genetic variation. The distribution and behavior of phenotypic variation in these
      populations suggest that stable epialleles can control complex quantitative
      traits. However, stochastic epimutation and transposon movement in these
      populations present some unexpected technical hurdles to implementing
      quantitative epigenetic analysis.

PMID- 19605681
TI  - Paused Pol II captures enhancer activity and acts as a potent insulator.
AB  - Enhancers act over many kilobase pairs to activate target promoters, but their
      activity is constrained by insulator elements that prevent indiscriminate
      activation of nearby genes. In the July 1, 2009, issue of Genes & Development,
      Chopra and colleagues (pp. 1505-1509) report that promoters containing a stalled
      Pol II are activated by enhancers, but these promoters also serve as insulators
      that block enhancers from reaching more distal genes. This new class of
      insulators provide critical clues to regulatory mechanisms.

PMID- 19605682
TI  - Interpreting spatial information and regulating mitosis in response to spindle
      orientation.
AB  - The spindle position checkpoint (SPOC) is a regulatory mechanism that ensures
      accurate segregation of chromosomes in polarized cells during mitosis. In this
      issue of Genes & Development, Chan and Amon (pp. 1639-1649) identify a
      phosphoprotein phosphatase (Rts1-PP2A) as a new member of the checkpoint in
      budding yeast and define its role in interpreting spatial information during
      mitosis.

PMID- 19605683
TI  - Cell type specificity of PI3K signaling in Pdk1- and Pten-deficient brains.
AB  - Loss of PTEN causes unregulated activation of downstream components of
      phosphatidylinositol 3-kinase (PI3K) signaling, including PDK1, and disrupts
      normal nervous system development and homeostasis. We tested the contribution of
      Pdk1 to the abnormalities induced by Pten deletion in the brain. Conditional
      deletion of Pdk1 caused microcephaly. Combined deletion of Pdk1 and Pten rescued
      hypertrophy, but not migration defects of Pten-deficient neurons. Pdk1
      inactivation induced strikingly different effects on the regulation of
      phosphorylated Akt in glia versus neurons. Our results show Pdk1-dependent and
      Pdk1-independent abnormalities in Pten-deficient brains, and demonstrate cell
      type specific differences in feedback regulation of the ubiquitous PI3K pathway.

PMID- 19605684
TI  - Epigenetic control of skull morphogenesis by histone deacetylase 8.
AB  - Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in
      mammalian development. Here we provide evidence that Hdac8 specifically controls
      patterning of the skull by repressing a subset of transcription factors in
      cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal
      lethality due to skull instability, and this is phenocopied by conditional
      deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the
      aberrant expression of homeobox transcription factors such as Otx2 and Lhx1.
      These findings reveal how the identity and patterning of vertebrate-specific
      portions of the skull are epigenetically controlled by a histone deacetylase.

PMID- 19605685
TI  - Paracrine signaling in a bacterium.
AB  - Cellular differentiation is triggered by extracellular signals that cause target
      cells to adopt a particular fate. Differentiation in bacteria typically involves
      autocrine signaling in which all cells in the population produce and respond to
      the same signal. Here we present evidence for paracrine signaling in bacterial
      populations-some cells produce a signal to which only certain target cells
      respond. Biofilm formation in Bacillus involves two centrally important signaling
      molecules, ComX and surfactin. ComX triggers the production of surfactin. In
      turn, surfactin causes a subpopulation of cells to produce an extracellular
      matrix. Cells that produced surfactin were themselves unable to respond to it.
      Likewise, once surfactin-responsive cells commenced matrix production, they no
      longer responded to ComX and could not become surfactin producers. Insensitivity
      to ComX was the consequence of the extracellular matrix as mutant cells unable to
      make matrix responded to both ComX and surfactin. Our results demonstrate that
      extracellular signaling was unidirectional, with one subpopulation producing a
      signal and a different subpopulation responding to it. Paracrine signaling in a
      bacterial population ensures the maintenance, over generations, of particular
      cell types even in the presence of molecules that would otherwise cause those
      cells to differentiate into other cell types.

PMID- 19605686
TI  - The protein phosphatase 2A functions in the spindle position checkpoint by
      regulating the checkpoint kinase Kin4.
AB  - In budding yeast, a surveillance mechanism known as the spindle position
      checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle
      misposition, the checkpoint delays exit from mitosis by restraining the activity
      of the mitotic exit network (MEN). To date, the only component of the checkpoint
      to be identified is the protein kinase Kin4. Furthermore, how the kinase is
      regulated by spindle position is not known. Here, we identify the protein
      phosphatase 2A (PP2A) in complex with the regulatory subunit Rts1 as a component
      of the SPOC. Loss of PP2A-Rts1 function abrogates the SPOC but not other mitotic
      checkpoints. We further show that the protein phosphatase functions upstream of
      Kin4, regulating the kinase's phosphorylation and localization during an
      unperturbed cell cycle and during SPOC activation, thus defining the phosphatase
      as a key regulator of SPOC function.

PMID- 19605687
TI  - SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes.
AB  - Spliceosomal small nuclear ribonucleoproteins (snRNPs) in trypanosomes contain
      either the canonical heptameric Sm ring (U1, U5, spliced leader snRNPs), or
      variant Sm cores with snRNA-specific Sm subunits (U2, U4 snRNPs). Searching for
      specificity factors, we identified SMN and Gemin2 proteins that are highly
      divergent from known orthologs. SMN is splicing-essential in trypanosomes and
      nuclear-localized, suggesting that Sm core assembly in trypanosomes is nuclear.
      We demonstrate in vitro that SMN is sufficient to confer specificity of canonical
      Sm core assembly and to discriminate against binding to nonspecific RNA and to U2
      and U4 snRNAs. SMN interacts transiently with the SmD3B subcomplex, contacting
      specifically SmB. SMN remains associated throughout the assembly of the Sm
      heteroheptamer and dissociates only when a functional Sm site is incorporated.
      These data establish a novel role of SMN, mediating snRNP specificity in Sm core
      assembly, and yield new biochemical insight into the mechanism of SMN activity.

PMID- 19605689
TI  - Regulation of transgenes in three-dimensional cultures of primary mouse mammary
      cells demonstrates oncogene dependence and identifies cells that survive
      deinduction.
AB  - The advent of targeted therapies for cancer has provoked interest in experimental
      models for the systematic study of oncogene dependence. To that end, we developed
      a three-dimensional (3D) culture system to analyze the responses of primary mouse
      mammary epithelial cells to the induction and deinduction of oncogenes. Mammary
      cells derived from normal virgin mice, or from tritransgenic mice (TetO-MYC;TetO
      Kras(G12D);MMTV-rtTA) in which MYC and mutant Kras can be regulated by
      doxycycline, develop from single cells into polarized acini. Lumen formation
      occurs without apparent apoptosis, and the hollow spheres of cells enlarge by
      division, with metaphase plates oriented perpendicularly to the apical surface.
      When MYC and Kras(G12D) are induced, the acini enlarge and form solid,
      depolarized spheres. Upon deinduction of MYC and Kras(G12D) the solid structures
      regress, leaving a repolarized monolayer of viable cells. These cells display a
      phenotype consistent with progenitors of mammary epithelium: They exclude Hoechst
      dye 33342, and reform acini in 3D cultures and repopulate mammary fat pads more
      efficiently than cells harvested from uninduced acini. Moreover, cells in the
      surviving spheres retain the ability to respond to reinduction and thus may
      represent the type of cells that give rise to recurrent tumors.

PMID- 19605688
TI  - Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A.
AB  - Precise control of the timing and magnitude of Notch signaling is essential for
      the normal development of many tissues, but the feedback loops that regulate
      Notch are poorly understood. Developing T cells provide an excellent context to
      address this issue. Notch1 signals initiate T-cell development and increase in
      intensity during maturation of early T-cell progenitors (ETP) to the DN3 stage.
      As DN3 cells undergo beta-selection, during which cells expressing functionally
      rearranged TCRbeta proliferate and differentiate into CD4(+)CD8(+) progeny,
      Notch1 signaling is abruptly down-regulated. In this report, we investigate the
      mechanisms that control Notch1 expression during thymopoiesis. We show that
      Notch1 and E2A directly regulate Notch1 transcription in pre-beta-selected
      thymocytes. Following successful beta-selection, pre-TCR signaling rapidly
      inhibits Notch1 transcription via signals that up-regulate Id3, an E2A inhibitor.
      Consistent with a regulatory role for Id3 in Notch1 down-regulation, post-beta
      selected Id3-deficient thymocytes maintain Notch1 transcription, whereas enforced
      Id3 expression decreases Notch1 expression and abrogates Notch1-dependent T-cell
      survival. These data provide new insights into Notch1 regulation in T-cell
      progenitors and reveal a direct link between pre-TCR signaling and Notch1
      expression during thymocyte development. Our findings also suggest new strategies
      for inhibiting Notch1 signaling in pathologic conditions.

PMID- 19605692
TI  - The diagnostic reliability of sexual sadism.
AB  - Previous studies have reported low diagnostic agreement on the paraphilias,
      especially sexual sadism. In the present study, 34 evaluators throughout the
      United States reviewed summaries of 12 committed sex offenders. The evaluators
      agreed more than 90% of the time on whether offenders met criteria for any
      paraphilia in general and sexual sadism in particular. The authors attribute the
      low reliability reported in previous studies to different agreement indices, the
      amount and quality of information available to evaluators, and the prevalence of
      the respective paraphilic diagnoses in their samples.

PMID- 19605691
TI  - A cumulative scale of severe sexual sadism.
AB  - The article assesses the scale properties of the criterion set for severe sexual
      sadism in a sample of male forensic patients (N = 100). Half of the sample
      consists of sexual sadists; the remainder is sampled at random from the general
      group of nonsadistic sex offenders. Eleven of 17 criteria (plus the additional
      item of inserting objects into the victim's bodily orifices) of Marshall,
      Kennedy, Yates, and Serran's list form a cumulative scale. More specifically,
      this scale comprises all the 5 core criteria that Marshall and his colleagues
      considered particularly relevant. The resulting 11-item scale of severe sexual
      sadism is highly reliable (r(tt) = .93) and represents a strong scale (H = .83)
      of the Guttman type (coefficient of reproducibility = .97). The 11-item scale
      distinguishes perfectly between sexual sadists and nonsadistic sex offenders in
      the sample.

PMID- 19605690
TI  - Removal of maternal retinoic acid by embryonic CYP26 is required for correct
      Nodal expression during early embryonic patterning.
AB  - The abundance of retinoic acid (RA) is determined by the balance between its
      synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In
      particular, the dynamic expression of three CYP26 genes controls the regional
      level of RA within the body. Pregastrulation mouse embryos express CYP26 but not
      RALDH. We now show that mice lacking all three CYP26 genes manifest duplication
      of the body axis as a result of expansion of the Nodal expression domain
      throughout the epiblast. Mouse Nodal was found to contain an RA-responsive
      element in intron 1 that is highly conserved among mammals. In the absence of
      CYP26, maternally derived RA activates Nodal expression in the entire epiblast of
      pregastrulation embryos via this element. These observations suggest that
      maternal RA must be removed by embryonic CYP26 for correct Nodal expression
      during embryonic patterning.

PMID- 19605693
TI  - Telomere shortening and oxidative stress in aged macrophages results in impaired
      STAT5a phosphorylation.
AB  - Macrophages are an essential component of both innate and adaptive immunity, and
      altered function of these cells with aging may play a key role in
      immunosenescence. To determine the effect of aging on macrophages, we produced
      bone marrow-derived macrophages in vitro. In these conditions, we analyzed the
      effect of aging on macrophages without the influence of other cell types that may
      be affected by aging. We showed that telomeres shorten with age in macrophages
      leading to a decreased GM-CSF but not M-CSF-dependent proliferation of these
      cells as a result of decreased phosphorylation of STAT5a. Macrophages from aged
      mice showed increased susceptibility to oxidants and an accumulation of
      intracellular reactive oxygen species. In these macrophages STAT5a oxidation was
      reduced, which led to the decreased phosphorylation observed. Interestingly, the
      same cellular defects were found in macrophages from telomerase knockout (Terc(-/
      )) mice suggesting that telomere loss is the cause for the enhanced oxidative
      stress, the reduced Stat5a oxidation and phosphorylation and, ultimately, for the
      impaired GM-CSF-dependent macrophage proliferation.

PMID- 19605694
TI  - The magnitude of CD4+ T cell recall responses is controlled by the duration of
      the secondary stimulus.
AB  - The parameters controlling the generation of robust CD4(+) T cell recall
      responses remain poorly defined. In this study, we compare recall responses by
      CD4(+) and CD8(+) memory T cells following rechallenge. Homologous rechallenge of
      mice immune to either lymphocytic choriomeningitis virus or Listeria
      monocytogenes results in robust CD8(+) T cell recall responses but poor boosting
      of CD4(+) T cell recall responses in the same host. In contrast, heterologous
      rechallenge with a pathogen sharing only a CD4(+) T cell epitope results in
      robust boosting of CD4(+) T cell recall responses. The disparity in CD4(+) and
      CD8(+) T cell recall responses cannot be attributed to competition for growth
      factors or APCs, as robust CD4(+) and CD8(+) T cell recall responses can be
      simultaneously induced following rechallenge with peptide-pulsed dendritic cells.
      Instead, CD4(+) T cell recall responses are dependent on the duration of the
      secondary challenge. Increasing the rechallenge dose results in more potent
      boosting of CD4(+) T cell recall responses and artificially limiting the duration
      of secondary infection following heterologous rechallenge adversely impacts the
      magnitude of CD4(+) T cell, but not CD8(+) T cell, recall responses. These
      findings suggest that rapid pathogen clearance by secondary CTL following
      homologous rechallenge prevents optimal boosting of CD4(+) T cell responses and
      therefore have important practical implications in the design of vaccination and
      boosting strategies aimed at promoting CD4(+) T cell-mediated protection.

PMID- 19605695
TI  - Critical roles of translationally controlled tumor protein in the homeostasis and
      TCR-mediated proliferation of peripheral T cells.
AB  - Translationally controlled tumor protein (TCTP) is expressed throughout T cell
      development and prominently induced following T cell activation. However, its
      function(s) during these processes is unclear. Here, we demonstrated that
      conditional deletion of TCTP before the beta selection checkpoint resulted into a
      partial block of thymocyte development at the double-negative (DN) 3 stage.
      Deletion of TCTP in the double-positive (DP) stage did not cause any significant
      phenotype in the thymus except a slight increase of mature CD8 single-positive
      (SP) thymocytes. In contrast to the very modest phenotype observed in the thymus,
      a significant reduction of mature T cells was observed in the peripheral lymphoid
      organs of these two conditional null TCTP mutant mice. Detailed analysis revealed
      that the latter phenotype (peripheral T cell lymphopenia) was largely due to a
      decreased viability of mature TCTP-deficient (TCTP(-/-)) T cells. Transgenic
      expression of the anti-apoptotic protein Bcl-2 rescued the partial block of early
      thymocyte development, but not peripheral T cell lymphopenia of T-lineage
      specific TCTP(-/-) mice, suggesting that the signaling networks of TCTP in these
      two processes are not identical. Last, we demonstrated that TCTP(-/-) T cells
      manifested a significant defect in T cell Ag receptor (TCR)-mediated cell
      proliferation. Further analysis revealed that such defect was due to a marked
      delay in the initial cell-cycle entry of TCTP(-/-) T cells following TCR
      stimulation. Together, these results indicate that TCTP plays a very modest role
      in thymocyte development, but is critical for peripheral T cell maintenance and
      TCR-mediated cell proliferation.

PMID- 19605696
TI  - Intracellular receptor for human host defense peptide LL-37 in monocytes.
AB  - The human cationic host defense peptide LL-37 has a broad range of
      immunomodulatory, anti-infective functions. A synthetic innate defense regulator
      peptide, innate defense regulator 1 (IDR-1), based conceptually on LL-37, was
      recently shown to selectively modulate innate immunity to protect against a wide
      range of bacterial infections. Using advanced proteomic techniques, ELISA, and
      Western blotting procedures, GAPDH was identified as a direct binding partner for
      LL-37 in monocytes. Enzyme kinetics and mobility shift studies also indicated LL
      37 and IDR-1 binding to GAPDH. The functional relevance of GAPDH in peptide
      induced responses was demonstrated by using gene silencing of GAPDH with small
      interfering RNA (siRNA). Previous studies have established that the induction of
      chemokines and the anti-inflammatory cytokine IL-10 are critical immunomodulatory
      functions in the anti-infective properties of LL-37 and IDR-1, and these
      functions are modulated by the MAPK p38 pathway. Consistent with that, this study
      demonstrated the importance of the GAPDH interactions with these peptides since
      gene silencing of GAPDH resulted in impaired p38 MAPK signaling, downstream
      chemokine and cytokine transcriptional responses induced by LL-37 and IDR-1, and
      LL-37-induced cytokine production. Bioinformatic analysis, using InnateDB, of the
      major interacting partners of GAPDH indicated the likelihood that this protein
      can impact on innate immune pathways including p38 MAPK. Thus, this study has
      demonstrated a novel function for GAPDH as a mononuclear cell receptor for human
      cathelicidin LL-37 and immunomodulatory IDR-1 and conclusively demonstrated its
      relevance in the functioning of cationic host defense peptides.

PMID- 19605697
TI  - Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1(+) smokers
      with early emphysema.
AB  - HIV1(+) smokers develop emphysema at an earlier age and with a higher incidence
      than HIV1(-) smokers. Since human alveolar macrophages (AMs) are capable of
      producing proteases that degrade extracellular matrix components, we hypothesized
      that up-regulation of AM matrix metalloproteinases may be associated with the
      emphysema of HIV1(+) smokers. Microarray analysis was used to screen which matrix
      metalloproteinases (MMPs) genes were expressed by AM of HIV1(+) smokers with
      early emphysema. For each of the MMP genes expressed (MMP-1, -2, -7, -9, -10, -12
      and -14), TaqMan PCR was used to quantify the relative expression in AM from four
      groups of individuals: HIV1(-) healthy nonsmokers, HIV1(-) healthy smokers, HIV1(
      ) smokers with early emphysema, and HIV1(+) smokers with early emphysema. While
      AM gene expression of MMPs was higher in HIV1(-) individuals with emphysema in
      comparison with HIV1(-) healthy smokers, for the majority of the MMPs (-1, -7, 
      9, and -12), AM expression from HIV1(+) smokers with early emphysema was
      significantly higher than in HIV1(-) smokers with early emphysema. HIV1(+)
      individuals with early emphysema also had higher levels of epithelial lining
      fluid (ELF) MMPs (-2, -7, -9, and -12) than the 3 HIV1(-) groups. ELF MMP (-2,-7,
      9, and -12) levels were similar in HIV1(+) nonsmokers compared with HIV1(-)
      nonsmokers. Interestingly, the active forms of MMP-2, -9, and -12 were
      exclusively detected in ELF from HIV1(+) individuals with early emphysema. Since
      the activities of the up-regulated AM MMPs include collagenases, gelatinases,
      matrilysins, and elastase, these data suggest that up-regulated AM MMP genes and
      activation of MMP proteins may contribute to the emphysema of HIV1(+) individuals
      who smoke.

PMID- 19605698
TI  - Functional plasticity of macrophages: in situ reprogramming of tumor-associated
      macrophages.
AB  - The extent to which the functional heterogeneity of Mvarphis is dependent on the
      differentiation of functional sublineages remains unresolved. One alternative
      hypothesis proposes that Mvarphis are functionally plastic cells, which are
      capable of altering their functional activities progressively in response to
      progressively changing signaling molecules generated in their microenvironment.
      This "functional plasticity" hypothesis predicts that the functionally polarized
      Mvarphis in chronic pathologies do not represent Mvarphi sublineages but rather,
      are mutable phenotypes sustained by chronic signaling from the pathological
      environment. Solid TAMvarphis are chronically polarized to provide activities
      that support tumor growth and metastasis and suppress adaptive immune responses.
      In support of the functional plasticity hypothesis, administration of slow
      release microsphere-encapsulated IL-12 successfully reprogrammed TAMvarphis in
      situ, reducing Mvarphi support of tumor growth and metastasis and enhancing
      Mvarphi proimmunogenic activities. Increased knowledge of how Mvarphi function is
      regulated and how polarized Mvarphis can be reprogrammed in situ will increase
      our ability to control Mvarphi function in a variety of pathological states,
      including cancer and chronic inflammatory disease.

PMID- 19605700
TI  - Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent
      with its role in myelodysplastic syndromes.
AB  - The oncogene EVI1 has been implicated in the etiology of AML and MDS. Although
      AML cells are characterized by accelerated proliferation and differentiation
      arrest, MDS cells hyperproliferate when immature but fail to differentiate later
      and die instead. In agreement with its roles in AML and in immature MDS cells,
      EVI1 was found to stimulate cell proliferation and inhibit differentiation in
      several experimental systems. In contrast, the variant protein MDS1/EVI1 caused
      the opposite effect in some of these assays. In the present study, we expressed
      EVI1 and MDS1/EVI1 in a tetracycline-regulable manner in the human myeloid cell
      line U937. Induction of either of these proteins caused cells to accumulate in
      the G(0)/G(1)-phase of the cell cycle and moderately increased the rate of
      spontaneous apoptosis. However, when EVI1- or MDS1/EVI1-expressing cells were
      induced to differentiate, they massively succumbed to apoptosis, as reflected by
      the accumulation of phosphatidylserine in the outer leaflet of the plasma
      membrane and increased rates of DNA fragmentation. In summary, these data show
      that inducible expression of EVI1 in U937 cells causes phenotypes that may be
      relevant for its role in MDS and provides a basis for further investigation of
      its contribution to this fatal disease.

PMID- 19605701
TI  - Jiangella alba sp. nov., an endophytic actinomycete isolated from the stem of
      Maytenus austroyunnanensis.
AB  - A novel actinomycete strain, YIM 61503T, isolated from the stem of Maytenus
      austroyunnanensis, was characterized by using a polyphasic approach. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain YIM 61503T belonged
      to the genus Jiangella and exhibited 16S rRNA gene sequence similarities of 98.8
      and 98.6% to Jiangella alkaliphila D8-87T and Jiangella gansuensis YIM 002T. The
      chemotaxonomic properties of strain YIM 61503T were consistent with those of the
      genus Jiangella: the cell-wall peptidoglycan type was based on ll-diaminopimelic
      acid and MK-9(H4) was the predominant menaquinone. The major fatty acids were
      anteiso-C15:0, iso-C16:0, iso-C14:0, C17:1omega8c and anteiso-C17:0. The DNA G+C
      content was 71.9 mol%. Strain YIM 61503T was phenotypically distinct from
      recognized Jiangella species and was shown to belong to a separate genomic
      species based on DNA-DNA hybridization results. Thus, strain YIM 61503T is
      considered to represent a novel species of the genus Jiangella, for which the
      name Jiangella alba sp. nov. is proposed. The type strain is YIM 61503T (=DSM
      45237T=CCTCC AA 208023T).

PMID- 19605702
TI  - Rhodoplanes pokkaliisoli sp. nov., a phototrophic alphaproteobacterium isolated
      from a waterlogged brackish paddy soil.
AB  - A Gram-negative, rod-shaped, purple non-sulfur bacterial strain, designated
      JA415T, was isolated from the mud of a pokkali rice field located on Vypeen
      Island, Ernakulam, Kerala, India. Strain JA415T was motile by means of a single
      polar flagellum. Photo- and chemo-organoheterotrophic growth was observed using
      organic compounds as carbon sources and electron donors. Photo- and
      chemolithoautotrophic growth using thiosulfate as electron donor did not occur.
      Fermentative growth could not be demonstrated. Intracellular photosynthetic
      membranes were lamellar stacks parallel to the cytoplasmic membrane.
      Bacteriochlorophyll a and carotenoids of the spirilloxanthin series were present
      as photosynthetic pigments. Niacin, pantothenate and p-aminobenzoate were
      required as growth factors. C18:1omega7c was the predominant cellular fatty acid
      component. Phylogenetic analysis based on 16S rRNA gene sequences showed that
      strain JA415T clustered with members of the genus Rhodoplanes in the class
      Alphaproteobacteria. On the basis of phenotypic and molecular genetic evidence,
      it is proposed that strain JA415T be classified as a representative of a novel
      species of the genus Rhodoplanes, family Hyphomicrobiaceae, with the name
      Rhodoplanes pokkaliisoli sp. nov. The type strain is JA415T (=KCTC 5711T=NBRC
      104972T).

PMID- 19605699
TI  - Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and
      transepithelial migration.
AB  - In airway cells, TLR2 stimulation by bacterial products activates Ca2+ fluxes
      that signal leukocyte recruitment to the lung and facilitates transepithelial
      migration into the airway lumen. TLR2 is apically displayed on airway cells,
      where it senses bacterial stimuli. Biochemical and genetic approaches demonstrate
      that TLR2 ligands stimulate release of Ca2+ from intracellular stores by
      activating TLR2 phosphorylation by c-Src and recruiting PI3K and PLCgamma to
      affect Ca2+ release through IP3Rs. This Ca2+ release plays a pivotal role in
      signaling TLR2-dependent NF-kappaB activation and chemokine expression to recruit
      PMNs to the lung. In addition, TLR2-initiated Ca2+ release activates Ca2+
      dependent proteases, calpains, which cleave the transmembrane proteins occludin
      and E-cadherin to promote PMN transmigration. This review highlights recent
      findings that demonstrate a central role for Ca2+ signaling in airway epithelial
      cells to induce proinflammatory gene transcription and to initiate junctional
      changes that accommodate transmigration of recruited PMNs.

PMID- 19605703
TI  - Jejuia pallidilutea gen. nov., sp. nov., a new member of the family
      Flavobacteriaceae isolated from seawater.
AB  - An aerobic, pale-orange-pigmented, Gram-stain-negative bacterium, designated
      strain EM39T, was isolated from seawater from the eastern coast of Jeju Island,
      Korea, and its taxonomic status was established using a polyphasic approach.
      Comparative 16S rRNA gene sequence studies revealed that strain EM39T formed a
      distinct lineage within the family Flavobacteriaceae and could be distinguished
      from strains of members of the related genera Gaetbulibacter, Mariniflexile and
      Tamlana by 16S rRNA gene sequence analysis (similarity values between strain
      EM39T and related strains were all less than 93.8%). Cells of strain EM39T were
      non-gliding, catalase- and oxidase-positive rods that were devoid of flexirubin
      pigments. Growth was observed at 15-35 degrees C (optimum, 25-30 degrees C) and
      pH 6.5-9.0 (optimum, pH 7.0-8.5). The genomic DNA G+C content was 34.6 mol% and
      the major respiratory quinone was MK-6. The predominant cellular fatty acids were
      iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH. On the basis of phenotypic and
      genotypic data, strain EM39T represents a novel species in a new genus in the
      family Flavobacteriaceae, for which the name Jejuia pallidilutea gen. nov., sp.
      nov. is proposed. The type strain is EM39T (=KCTC 22298T=DSM 21165T).

PMID- 19605705
TI  - Mesorhizobium australicum sp. nov. and Mesorhizobium opportunistum sp. nov.,
      isolated from Biserrula pelecinus L. in Australia.
AB  - Biserrula pelecinus L. is a pasture legume that was introduced to Australia from
      the Mediterranean basin in 1993. Although the native rhizobial population could
      not nodulate B. pelecinus at the time of its introduction, recent research has
      shown the emergence of a diversity of strains (novel isolates) that are able to
      do so. Three novel isolates, WSM2073T, WSM2074 and WSM2076, had nearly identical
      16S rRNA gene sequences, and clustered separately with all recognized species of
      the genus Mesorhizobium. Conversely, the novel isolate WSM2075T had >23 nt
      mismatches with the above three isolates. All four novel isolates shared 97-99%
      16S rRNA gene sequence similarity with the type strains of all recognized
      Mesorhizobium species. However, strains WSM2073T, WSM2074 and WSM2076 showed
      <95.2% dnaK gene sequence similarity to the type strains of recognized
      Mesorhizobium species, and <92.9% to WSM2075T (which also shared <95.5% dnaK gene
      sequence similarity to the type strains of recognized Mesorhizobium species).
      Results for GSII gene sequencing were consistent with those for the dnaK gene.
      The fatty acid profiles of the novel isolates were diagnostic of root-nodule
      bacteria, but did not match those of recognized bacterial species. Strain
      WSM2075T had a significantly different fatty acid profile from the other three
      isolates. The above results indicated that strains WSM2073T, WSM2074 and WSM2076
      represent the same species. Strain WSM2073T showed <45% DNA-DNA relatedness and
      WSM2075T<5% DNA-DNA relatedness with the type strains of recognized Mesorhizobium
      species; these two novel isolates shared 59% DNA-DNA relatedness. Collectively,
      these data indicate that strains WSM2073T, WSM2074 and WSM2076, and strain
      WSM2075T belong to two novel species of the genus Mesorhizobium, for which the
      names Mesorhizobium australicum sp. nov. and Mesorhizobium opportunistum sp. nov.
      are proposed, respectively. The type strain of Mesorhizobium australicum sp. nov.
      is WSM2073T (=LMG 24608T=HAMBI 3006T) and the type strain of Mesorhizobium
      opportunistum sp. nov. is WSM2075T (=LMG 24607T=HAMBI 3007T).

PMID- 19605704
TI  - Streptomyces baliensis sp. nov., isolated from Balinese soil.
AB  - The taxonomic positions of actinomycete strains ID03-0915T and ID03-0825,
      isolated from soil on the Indonesian island of Bali, were examined using a
      polyphasic taxonomic approach. The morphological and chemotaxonomic
      characteristics of these organisms are typical of the genus Streptomyces.
      Phylogenetic analyses performed using almost-complete 16S rRNA gene sequences
      demonstrated that the strains were closely related to Streptomyces glauciniger
      and Streptomyces lilacinus. However, DNA-DNA hybridization and phenotypic
      characteristics revealed that the strains differed from known Streptomyces
      species. Therefore, we conclude that strains ID03-0915T and ID03-0825 (=BTCC B
      563) represent a novel species of the genus Streptomyces, for which we propose
      the name Streptomyces baliensis sp. nov. The type strain is strain ID03-0915T
      (=BTCC B-608T=NBRC 104276T).

PMID- 19605706
TI  - Vibrio hangzhouensis sp. nov., isolated from sediment of the East China Sea.
AB  - Strain CN83T, a Gram-negative, aerobic, rod-shaped bacterium, was isolated from
      sediment of the East China Sea. The isolate was catalase- and oxidase-positive
      and cells were motile by means of polar flagella. The DNA G+C content was 44.9
      mol%. The major fatty acids were C16:1omega7c and/or iso-C15:0 2-OH, C16:0,
      C18:1omega7c, C14:0 and C12:0. 16S rRNA gene sequence analysis showed that strain
      CN83T belonged to the genus Vibrio and had the highest sequence similarity to
      Vibrio agarivorans (98.4%) and Vibrio campbellii (97.8%). Phylogenetic analysis
      revealed that strain CN83T formed a monophyletic clade adjacent to the type
      strain of V. agarivorans. The DNA-DNA hybridization values of strain CN83T with
      V. agarivorans DSM 13756T and V. campbellii DSM 19270T were 44.6 and 25.5%,
      respectively. On the basis of the phenotypic and genotypic data, strain CN83T
      represents a novel species of the genus Vibrio, for which the name Vibrio
      hangzhouensis sp. nov. is proposed. The type strain is CN83T (=CGMCC 1.7062T=JCM
      15146T).

PMID- 19605707
TI  - Paraoerskovia marina gen. nov., sp. nov., an actinobacterium isolated from marine
      sediment.
AB  - A Gram-positive-staining, facultatively anaerobic bacterial strain, CTT-37T, was
      isolated from a marine sediment sample collected from Tottori city, located on
      the shore of the Sea of Japan. A 16S rRNA gene sequence comparison indicated that
      the isolate represents a novel clade that clusters with members of the families
      Cellulomonadaceae and Sanguibacteraceae. Strain CTT-37T shared maximum 16S rRNA
      gene sequence similarity of 96.4% with Oerskovia paurometabola DSM 14281T and
      96.2% with Oerskovia enterophila DSM 43852T. The DNA-DNA hybridization value
      between strain CTT-37T and O. enterophila JCM 7350T was 10-12%. The following
      chemotaxonomic characteristics of strain CTT-37T were markedly different from
      those of strains in the genus Oerskovia. The cell wall contained L-serine in the
      peptidoglycan interpeptide bridge. The predominant menaquinone was MK-9 (H4);
      other quinones detected were MK-9 and MK-9(H2). The only polar lipid was
      phosphatidylglycerol and the G+C content of the DNA was 70 mol%. Differences in
      phenotypic characteristics and large phylogenetic distances between strain CTT
      37T and all members of the genus Oerskovia supported the classification of CTT
      37T within a new genus and species, for which the name Paraoerskovia marina gen.
      nov., sp. nov. is proposed. The type strain of Paraoerskovia marina is CTT-37T
      (=NBRC 104352T=DSM 21750T).